eK0n0mi taK seriU$ d/h ekonomitakserius@blogspot.com

April 17, 2018

ya sudah lah: likopen BWAT tulang, loh :) : 201110_plasebo v. keyakinan publik (17 April 2018)

Filed under: Medicine — bumi2009fans @ 2:30 am

 

KOMPAS.com – Beberapa hari belakangan, pemberitaan publik dipenuhi dengan kontroversi terapi cuci otak ala dokter Terawan Agus Putranto. Kasus ini menjadi perhatian setelah kepala Rumah Sakit Pusat Angkatan Darat (RSPAD) Gatot Subroto itu diberi sanksi oleh Majelis Kehormatan Etik Kedokteran (MKEK) Ikatan Dokter Indonesia (IDI). Sanksi yang diberikan berupa pemecatan sementara selama satu tahun yang disertai dengan pencabutan izin praktik Terawan. Hal ini memicu perdebatan di kalangan publik. Apalagi, setelah banyak orang mengaku sembuh dengan terapi cuci otak ini. Tak tinggal diam, IDI kemudian menunda amar keputusan tersebut. Meski begitu, kontroversi tentang terapi ala Terawan tak kunjung reda. Baca juga: Kemenkes Belum Terima Surat Resmi dari IDI untuk Uji Terapi Terawan Salah satu yang menjadi perdebatan adalah terapi cuci otak ini hanya dianggap bersifat plasebo. Namun, apa sebenarnya plasebo itu? Mengenal Plasebo Dirangkum dari opini A Fauzi Yahya, seorang dokter spesialis jantung dan pembuluh darah pada Harian Kompas, Rabu (11/04/2018), plasebo didefinisikan sebagai terapi obat-obatan dan prosedur medis tanpa memiliki kandungan terapi. Meski tak punya kandungan terapi, plasebo beperan untuk menghilangkan atau meredakan keluhan pasien. “Termasuk dalam plasebo adalah bentuk komunikasi, situasi lingkungan, sentuhan tangan, dan sikap-sikap lain yang menyentuh emosi pasien,” tulis Fauzi. Efek plasebo ini biasanya bersifat subyektif pada setiap pasien. Meski berbeda-beda bagi tiap pasien; plasebo bisa meringankan kecemasan, depresi, hingga keluhan sakit pasien. Plasebo, baik obat maupun tindakan medis, tidak mengubah perjalanan penyakit ataupun menurunkan kematian akibat penyakit tersebut. “Jadi, jika kita kembali ke terapi cuci otak untuk mengatasi pembuluh yang tersumbat, baik di otak maupun jantung, tindakan yang bersifat plasebo tidak efektif memperbaiki aliran darah, tetapi berpotensi meringankan keluhan yang ada,” tulis Fauzi. Fauzi juga mengambil contoh yakni penderita kanker. Menurut dia, plasebo berperan mengurangi efek samping kemoterapi, tetapi tidak menghambat pertumbuhan tumor. “Plasebo meringankan secara dramatis sesak asma, tetapi tidak memengaruhi tes faal paru,” jelas Fauzi. Lalu apa sebenarnya efek plasebo ini? Fauzi menjelaskan, riset klinis terbaru membuktikan bahwa efek plasebo sebenarnya merupakan biopsikososial. Dia juga menyebut bahwa studi genetik masa kini telah mulai mampu mengidentifikasi pasien yang sangat responsif terhadap plasebo. Baca juga: Terapi Cuci Otak Dokter Terawan Bisa Obati Stroke? Ini Kata Ahli “Efek plasebo berkaitan dengan mekanisme kompleks neurobiologis yang melibatkan neurotransmiter (endorfin, cannabinoids, dan dopamin),” tulisnya. “Plasebo dapat menstimulasi respons psikologis, mulai dari laju jantung, tekanan darah, hingga aktivitas berbagai area otak,” imbuhnya. Berabad Lalu Efek plasebo bukan baru-baru ini saja dikenal. Bahkan, hal ini telah diketahui sejak berabad-abad lampau. “Kisah paling terkenal adalah tentang tongkat ajaib dokter Elisha Perkins yang muncul pada akhir abad ke-18,” ungkap Fauzi. “Dokter Perkins mampu membuat orang sakit yang terbaring lama kembali berdiri dan berjalan,” sambungnya. Sebelumnya, tak pernah ada dokter dengan kemampuan serupa di Connecticut, AS. Hanya dengan menyentuhkan tongkat bajanya saja, Perkins seolah-olah bisa menghilangkan penyakit seseorang. Kehebatan Perkins segera menyebar dari Amerika hingga Eropa Barat. Bisa dibayangkan, banyak orang berduyun-duyun mendatanginya untuk kesembuhan. “Tidak kurang 5.000 orang tersembuhkan dan proses penyembuhan itu tersertifikasi oleh 8 profesor, 40 dokter, dan 30 pendeta, termasuk presiden AS kala itu,” tulis Fauzi. “Namun, asosiasi kedokteran Connecticut memecat Perkins dari keanggotaan karena menganggap terapinya sebagai bualan,” tambahnya. Untuk membuktikan apakah yang terjadi pada pasien-pasien Perkins hanya efek plasebo, seorang dokter di Inggris melakukan hal yang sama. Baca juga: Amankah Menjalani Terapi Cuci Otak? Adalah John Haygarth yang melakukan itu. Dia mengganti tongkat baja ala Perkins dengan tongkat kayu yang mirip logam. Hasilnya, efek serupa dengan yang terjadi pada pasien Perkins terjadi. Dengan begitu, Haygarth membuktikan bahwa tongkat milik Perkins tak lebih dari plasebo. “Dia kemudian menulis buku berjudul Imagination as a cause and as a Cure of Disorder of the Body,” kisah Fauzi. Berhak Meragukan Cerita tentang efek plasebo tak hanya yang seajaib tongkat Perkins. Berbagai terapi yang merupakan tindakan medis pun bisa jadi hanya plasebo. “Euforia dunia atas keberhasilan tindakan renal denervation, yaitu intervensi pembuluh darah ginjal dalam mengatasi hipertensi membandel segera surut saat Dr Deepak L Bhatt dan kawan-kawan memublikasikan studi Symplicity HTN-3,” tulis Fauzi. “Studi yang dimuat di The New England Journal of Medicine pada 2014 itu membuktikan (bahwa) penurunan tekanan darah pada kelompok pasien yang mendapat terapi invasif tidak berbeda dengan kelompok pasien dengan prosedur plasebo (sham control),” sambungnya. Penelitian tersebut menjadi bukti bahwa terapi sebelumnya tidak benar-benar memberikan efek kesembuhan. Bahkan, dari temuan ini, terapi renal denervation tak lagi direkomendasikan hingga ada bukti berikutnya. Hal serupa juga terjadi dalam kedokteran jantung. Fauzi menjelaskan bahwa belum lama ini sebuah penelitian yang dipublikasikan dalam jurnal The Lancet membuktikan adanya efek plasebo pemasangan stent pada penderita penyakit jantung koroner stabil. Dalam penelitian yang dilakukan oleh Dr Rasha Al-Lamee dan koleganya, tidak didapati perbedaan hasil dalam kurun enam minggu pada mereka yang menjalani pemasangan stent jantung dan yang menjalani pemasangan stent pura-pura (sham control). “Studi Al-Lamee dan kawan-kawan memang belum menisbikan studi-studi besar peran intervensi koroner,” tulisnya. Baca juga: Terapi Cuci Otak Tak Bisa Cegah dan Obati Stroke ”

Namun, tak urung studi ini menegaskan profesi medis selalu berhak meragukan manfaat terapi walaupun terapi tersebut sudah berjalan empat dekade pada jutaan pasien,” tegasnya.

Menelaah ” Cuci Otak” Berkaca pada banyak kasus dunia tentang efek plasebo tersebut, Fauzi menyebut perlunya uji klinis yang tepat pada kasus Terawan. “Terkait untuk menguji apakah efek terapi dokter Terawan itu plasebo atau bukan, diperlukan suatu desain uji klinis yang tepat untuk menjawab segala keraguan,” ungkapnya. “Dokter Terawan akan jadi ikon kebanggaan bangsa jika terapi ini memang benar-benar berperan dalam mengatasi bahkan mencegah stroke yang menjadi salah satu penyebab kematian tertinggi di Indonesia,” imbuhnya.

Untuk itu, menurut Fauzi, perlu ada peran serta dari Kementerian Kesehatan (Kemenkes). “Tim Health Technology Asessment (HTA) Kementerian Kesehatan berperan menilai terapi metode cuci otak ini,” tulisnya. “Jika Kemenkes memandang terapi ini bermanfaat, tentu peserta BPJS berpotensi menikmati terapi ini, bukan sekadar mereka yang punya uang,” tegasnya.

Fauzi juga menilai hebohnya terapi cuci otak ini merupakan kesempatan yang baik untuk membuktikan manfaat terapi ini. “Keriuhan terapi cuci otak ini merupakan kesempatan baik bagi kalangan medis dari berbagai institusi untuk membuktikan tanggung jawab dan profesionalisme dalam memberikan perlindungan kepada masyarakat,” tulisnya. Baca juga: Antara Rompi Kanker Warsito dan Cuci Otak Terawan

Artikel ini telah tayang di Kompas.com dengan judul “Mengenal Efek Plasebo yang Sering Disebut pada “Cuci Otak” Terawan”, https://sains.kompas.com/read/2018/04/14/200500323/mengenal-efek-plasebo-yang-sering-disebut-pada-cuci-otak-terawan.
Penulis : Resa Eka Ayu Sartika
Editor : Shierine Wangsa Wibawa

gifi

Tulang Kuat dengan Tomat
Sabtu, 20 November 2010 | 09:12 WIB
shutterstock

Kompas.com – Ini adalah cara enak untuk membuat tulang makin kuat sehingga kita akan terhindar dari risiko penyakit osteoporosis, yakni minum jus tomat setiap hari.

Likopen, kandungan antioksidan dalam buah tomat, diyakini para ahli sebagai penyebab tulang bertambah kuat. Sebelumnya likopen sudah diketahui bermanfaat untuk mencegah kanker prostat pada pria dan juga mencegah penyakit jantung.

Dalam sebuah penelitian yang dilakukan di Kanada, para ahli meminta 60 orang wanita pasca menopause atau sekitar usia 50-60 tahun untuk menghentikan konsumsi produk tomat dari menu hariannya selama satu bulan.

Ternyata hal ini meningkatkan kadar N-telopeptide dalam darah, yakni zat kimia yang dilepaskan tubuh dalam darah ketika ada tulang yang patah.

Kemudian, selama empat bulan para responden penelitian diberikan jus tomat yang mengandung 15 mg likopen setiap hari, selain juga ditambah dengan 35 mg kapsul likopen. Sebagai kelompok kontrol ada responden yang mendapatkan kapsul plasebo.

Hasilnya kadar N-telopeptide pada wanita yang minum jus tomat atau kapsul likopen menurun drastis. Namun manfaat itu tidak didapatkan oleh wanita yang mengonsumsi kapsul plasebo.

Sebagai tindakan pencegahan, para ahli menyarankan konsumsi dua gelas jus tomat setiap hari. Hasil penelitian tersebut dipublikasikan dalam jurnal Osteoporosis International.
Nutrition News Desk
LYCOPENE BONE BOOSTER
Eat More Tomatoes, Watermelon, Guava

Want to build stronger bones? Then eat more tomatoes, watermelon, guava and red grapefruit. All contain lycopene, the red-pigmented antioxidant whose long list of benefits include heart health and protection against various cancers. The latest evidence points to a lower osteoporosis risk.

Tufts researchers compared dietary intake data with measurements of bone mineral density (BMD) among 600+ elderly volunteers over the course of four years. Among various antioxidant carotenoids tested (e.g., beta-carotene, lutein, etc.), lycopene appeared to confer the biggest bone-boosting benefit. Women in the top third of lycopene intake enjoyed 66% less bone loss than those with lower intakes. While men did not share this association, lycopene offers them other gender-specific benefits, such as a 28% lower risk of prostate cancer.

Beyond red-hued produce, other research has found that doubling fruit and vegetable intake bolstered bone strength among both male and female adolescents. In particular, prebiotic Superfoods like bananas, asparagus, leeks, onions, garlic and artichokes support bone health by enhancing calcium absorption. Also, try top sources of vitamin K– leafy greens, celery, broccoli, cabbage– to reduce fracture risk. Fruit and vegetables also help you avoid excess fat mass, which has been linked to lower bone mineral density. Learn more by checking out our “10 Dietary Habits for Better Bone Health” at http://www.dole.com/nutritioninsitute.

Osteoporos Int. 2007 Jan;18(1):109-15. Epub 2006 Aug 29.
Lycopene consumption decreases oxidative stress and bone resorption markers in postmenopausal women.

Rao LG, Mackinnon ES, Josse RG, Murray TM, Strauss A, Rao AV.

Division of Endocrinology and Metabolism, Department of Medicine, St. Michael’s Hospital, Toronto, ON, Canada. leticia.rao@utoronto.ca
Abstract

INTRODUCTION: Oxidative stress induced by reactive oxygen species (ROS) is associated with the risk of osteoporosis, and can be reduced by certain dietary antioxidants. Lycopene is an antioxidant known to decrease the risk of age-related chronic diseases, such as cancer. However, the role of lycopene in osteoporosis has not yet been investigated.

MATERIALS AND METHODS: In a cross-sectional study, 33 postmenopausal women aged 50-60 years provided seven-day dietary records and blood samples. Serum samples were used to measure serum lycopene, lipid peroxidation, protein thiols, bone alkaline phosphatase (BAP), and cross-linked N-telopeptides of type I collagen (NTx). The serum lycopene per kilogram body weight of the participants was grouped into quartiles and associated with the above serum parameters using one-way ANOVA and the Newman-Keuls post-test.

RESULTS: The results showed that groups with higher lycopene intake, as determined from the dietary records, had higher serum lycopene (p<0.02). A higher serum lycopene was found to be associated with a low NTx (p<0.005). Similarly, groups with higher serum lycopene had lower protein oxidation (p<0.05).

DISCUSSION: In conclusion, these results suggest that the dietary antioxidant lycopene reduces oxidative stress and the levels of bone turnover markers in postmenopausal women, and may be beneficial in reducing the risk of osteoporosis.

PMID: 16941193 [PubMed – indexed for MEDLINE]

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April 11, 2018

ya sudah lah: alkohol TERburuk … 011110_110418

Filed under: Medicine — bumi2009fans @ 3:51 am

tax scares

JAKARTA asahi shimbun–Deaths from drinking toxic bootleg alcohol in Indonesia have exceeded 100 this month, police said Wednesday as they vowed a “scorched earth” crackdown on the makers and distributors of black-market liquor.

Deputy National Police Chief Muhammad Syafruddin said deaths this month have been concentrated in populous West Java and Jakarta, the capital, but there were also cases in South Kalimantan and other regions that bring fatalities to more than 100.

Indonesian TV has broadcast images of distraught relatives in several cities and lines of gurneys bearing dead bodies in hospital hallways as the death toll relentlessly climbed since late last week. There were 31 deaths in Jakarta and satellite cities at the beginning of the month followed by a dramatic surge in hospitalizations and deaths in West Java.

“This is a crazy phenomenon,” Syafruddin said. “If we let it continue, it will harm the nation,” he said.

“I have ordered all the police chiefs in Indonesia to make these cases stop, zero victims, meaning to reveal the roots ranging from the producers, distributors, sellers to those who have the idea of mixing alcohol with fatal chemicals,” Syafruddin told reporters.

Police displayed huge quantities of suspect confiscated alcohol at their news conference, some of it in the small clear plastic bags that it’s sold in as well as professionally labeled bottles purporting to be whiskey or wine.

Syafruddin said production of illegal alcohol must be eradicated completely with a scorched earth campaign and called for the cooperation of Cabinet and government agencies.

It’s unclear how effective the crackdown will be. Curbs on sales of legal alcohol in Muslim-majority Indonesia, including a ban on sales from tens of thousands of convenience stores, have created a significant black market for bootleg liquor among the country’s poor.

Potentially lethal methanol can be a byproduct of bootleg distilling and the tainted alcohol is also sometimes mixed with soft drinks. In the recent spate of deaths, police said pure alcohol was sometimes combined with ingredients such as cough mixture and insect repellant.

Syafruddin said laboratory testing of black-market alcohol sized by police in several raids in Jakarta showed it contained methanol.

Deaths from toxic alcohol are common in Indonesia and foreigners are occasionally among the victims. Some governments warn travelers to the Indonesian islands of Bali and Lombok to be cautious about consuming local spirits and alcoholic beverages.

But the latest cluster of fatalities is extreme, leading to speculation that a single large distributor was responsible. But West Java police, who have arrested seven people suspected of mixing or selling tainted alcohol, said they have not found evidence to support that.

The Kompas newspaper said there were 32 deaths last year from drinking bootleg liquor.

 

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Drug experts say alcohol worse than crack or heroin
Photo
10:23am EDT

By Kate Kelland

LONDON (Reuters) – Alcohol is a more dangerous drug than both crack and heroin when the combined harms to the user and to others are assessed, British scientists said Monday.

Presenting a new scale of drug harm that rates the damage to users themselves and to wider society, the scientists rated alcohol the most harmful overall and almost three times as harmful as cocaine or tobacco.

According to the scale, devised by a group of scientists including Britain’s Independent Scientific Committee on Drugs (ISCD) and an expert adviser to the European Monitoring Center for Drugs and Drug Addiction (EMCDDA), heroin and crack cocaine rank as the second and third most harmful drugs.

Ecstasy is only an eighth as harmful as alcohol, according to the scientists’ analysis.

Professor David Nutt, chairman of the ISCD, whose work was published in the Lancet medical journal, said the findings showed that “aggressively targeting alcohol harms is a valid and necessary public health strategy.”

He said they also showed that current drug classification systems had little relation to the evidence of harm.

Alcohol and tobacco are legal for adults in Britain and many other countries, while drugs such as ecstasy and cannabis and LSD are often illegal and carry the threat of prison sentences.

“It is intriguing to note that the two legal drugs assessed — alcohol and tobacco — score in the upper segment of the ranking scale, indicating that legal drugs cause at least as much harm as do illegal substances,” Nutt, who was formerly head of the influential British Advisory Council on the Misuse of Drugs (ACMD), said in a statement about the study.

Nutt was forced to quit the ACMD a year ago after publicly criticizing ministers for ignoring scientific advice suggesting cannabis was less harmful than alcohol.

The World Health Organization estimates that risks linked to alcohol cause 2.5 million deaths a year from heart and liver disease, road accidents, suicides and cancer — accounting for 3.8 percent of all deaths. It is the third leading risk factor for premature death and disabilities worldwide.

In an effort to offer a guide to policy makers in health, policing, and social care, Nutt’s team rated drugs using a technique called multicriteria decision analysis (MCDA) which assessed damage according to nine criteria on harm to the user and seven criteria on harm to others.

Harms to the user included things such as drug-specific or drug-related death, damage to health, drug dependence and loss of relationships, while harms to others included crime, environmental damage, family conflict, international damage, economic cost, and damage to community cohesion.

Drugs were then scored out of 100, with 100 given to the most harmful drug and zero indicating no harm at all.

The scientists found alcohol was most harmful, with a score of 72, followed by heroin with 55 and crack with 54.

Among some of the other drugs assessed were crystal meth (33), cocaine (27), tobacco (26), amphetamine or speed (23), cannabis (20), benzodiazepines, such as Valium (15), ketamine (15), methadone (14), mephedrone (13), ecstasy (9), anabolic steroids (9), LSD (7) and magic mushrooms (5).

(Editing by Alison Williams)

Januari 22, 2018

pelan-pelan saja: Kurus Tiap Hari, Makan Telur

Filed under: Medicine — bumi2009fans @ 5:20 pm

Rabu, 10/03/2010 08:10 WIB

Makan Telur Tiap Hari Dapat Menurunkan Berat Badan

Merry Wahyuningsih – detikHealth

London, Makan telur sangat mengenyangkan terlebih lagi semua kandungan protein dan zat gizi di dalamnya terpenuhi. Makan telur tiap hari membuat orang gampang merasa kenyang sehingga bisa menurunkan berat badan.

Itulah mengapa pada tahun 1979, mantan perdana menteri Inggris Margaret Thatcher bisa mengurangi berat badannya dalam jangka waktu singkat dengan mengonsumsi 28 butir telur dalam seminggu.

Telur selama ini dianggap sebagai makanan yang tinggi kalori dan menyebabkan kolesterol tinggi. Ternyata kandungan kalori telur ukuran sedang hanya 80 kalori.

Makan sebutir telur tiap hari mencukupi kebutuhan 20 persen konsumsi harian manusia. Sehingga setelah makan telur orang tidak perlu lagi berlebihan mengonsumsi makanan lainnya.

Sebuah tim peneliti yang melakukan penelitian di Amerika Serikat menemukan bahwa orang yang makan telur memiliki hampir semua zat gizi yang lebih tinggi daripada orang yang tak mengonsumsi telur.

“Manfaat kesehatan dari telur tampak sangat besar. Sehingga mungkin tidak berlebihan jika menyebutnya makanan super. Telur merupakan makanan yang paling bergizi dari semua makanan yang ada,” kata Dr Carrie Ruxton, seorang ahli diet independen dan penulis laporan, seperti dilansir dari Dailymail, Rabu (10/3/2010).

Telur bisa dianggap ‘makanan super’ karena selain dapat meningkatkan kesehatan juga dapat melawan obesitas. Dan menurut ahli gizi, makan telur satu butir sehari dapat menurunkan berat badan.

Studi yang dirilis ini akan dipublikasikan pada bulan Juni dalam jurnal Nutrition and Food Science. Studi ini meneliti 71 penelitian dan bahan referensi yang memeriksa komposisi gizi telur dan perannya sebagai makanan.

Peneliti menemukan bahwa telur tidak hanya rendah kalori, tetapi juga merupakan sumber kaya protein dan dikemas dengan zat gizi yang penting bagi kesehatan, terutaman vitamin D, vitamin B12, selenium, dan kolin. Telur adalah makanan ideal pada setiap tahap kehidupan serta mudah dimasak dan menyenangkan untuk dimakan.

Sebuah laporan juga menegaskan bahwa diantara makanan protein, telur mengandung campuran asam amino esensial terkaya. Ini sangat penting untuk anak-anak, remaja, dewasa muda karena keseimbangan yang tepat diperlukan untuk pertumbuhan dan perbaikan. Dalam telur juga ditemukan antioksidan yang tinggi, yang dapat membantu mencegah penuaan terkait macular degeneration yang menyebabkan kebutaan.

Kelompok-kelompok tertentu yang mendapatkan manfaat dengan makan lebih banyak telur yaitu kaum muda, pecinta daging dan orang-orang yang menghindari susu.

Temuan kunci adalah bahwa telur merupakan makanan penting sumber vitamin D dan dapat memberikan kontribusi yang signifikan untuk meningkatkan asupan harian vitamin D.

Rendahnya kadar vitamin D dikaitkan dengan sejumlah kondisi medis seperti kerusakan tulang, kanker, penyakit jantung, multiple sclerosis, gangguan kekebalan tubuh dan masalah-masalah kesehatan mental.

Temuan terbaru yang didanai oleh British Egg Industry Council, mengatakan bahwa satu atau dua telur sehari tidak berpengaruh pada kolesterol total bagi kebanyakan orang.

Menurut Dr Ruxton, ada manfaat gizi yang nyata bila makan telur tiap hari. Bukti menunjukkan bahwa telur dapat berguna untuk mengenyangkan, mengendalikan berat badan dan juga untuk kesehatan mata.

(mer/ir)

bird

Jakarta – Sudah ngopi? Kalau suka kopi dan sedang turunkan berat badan, tambahkan satu butir telur. Menurut ahli nutrisi bisa bantu turunkan berat badan.

Menambahkan susu ke dalam kopi sudah biasa dilakukan. Jika sedang berdiet umumnya orang memilih susu rendah lemak atau tanpa lemak. Beberapa praktisi olahraga justru menganjurkan minum kopi sebelum olahraga agar lebih berenergi.

Kopi hitam yang dicampur dengan telur sudah jadi minuman tradisional banyak negara. Seperti Hungaria, Skandinavia, Vietnam dan Minnesota. Mereka mengonsumsi minuman ini sejak berabad silam.

Tambahkan Telur ke Dalam Kopi Agar Berat Badan Cepat TurunFoto: Grandyos Zafna

Para ahli nutrisi menganjurkan untuk menambahkan telur segar ke dalam kopi atau teh panas agar berat badan cepat turun, lapot the health site (21/1). Apa alasannya? Marc Bubbs, director nutrisi Canadian Men’s National Basketball mengatakan bahwa kombinasi antara kopi dan telur merupakan minuman populer di kalangan praktisi olahraga. Mereka minum kopi telur sebelum melalukan latihan kardio di pagi hari. Nutrisi dari telur akan membuat mereka lebih berenergi sehingga lebih banyak kalori terbakar dalam latihan.

Konsumsi telur mentah diketahui sangat berbahaya. Karena bisa terkontaminasi bakteri salmonella yang bisa sebabkan sakit perut dan yang fatal berujung kematian. Tetapi telur mentah aman dicampurkan ke dalam kopi karena panas kopi akan cukup untuk mematikan bakteri.

Telur perlu dimatangkan pada suhu 70 C, sementara suhu air kopi sekitar 90 C. Suhu ini cukup untuk membantu mematikan bakteri. Karenanya dianjurkan untuk membeli telur pasteurisasi.

 

Di Indonesia teh campur telur mentah biasa dinikmati di Sumatra Barat dan dikenal sebagai teh talua. Sedangkan kopi dicampur dengan telur biasa dikonsumsi di Vietnam dikenal dengan nama Ca Phe Trung.

Telur diambil kuningnya saja lalu dikocok hingga berbuih halus kemudian dituangkan ke dalam kopi panas dan diaduk. Agar tetap hangat hingga tetes terakhir, kopi telur Vietnam disajikan dalam gelas pendek.

Kemudian gelas ditaruh dalam mangkuk berisi air panas. Bahkan ada kafe di Saigon yang memberikan sensasi gurih enak yang lebih. Mereka memberi campuran mentega dan keju dalam kuning telur yang dikocok. Rasanya lebih creamy dan manis enak.

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Jakarta detik, Konsumsi buah-buahan sangat dianjurkan bagi kesehatan tubuh. Namun tak sedikit pula yang ragu karena merasa kebiasaan makan buah manis dapat menimbulkan risiko diabetes.

Jika Anda salah satunya, maka kini Anda tak perlu khawatir berlebihan. Studi terbaru menunjukkan bahwa gula di buah-buahan tidak sama seperti pemanis yang ada di gula pasir, soda dan makanan manis.

Gula alami ini juga tidak sama seperti madu, gula tebu, sirup jagung tinggi fruktosa, dan bentuk lain dari gula yang biasa ditambahkan ke banyak makanan olahan. Dikonsumsi bersamaan dengan serat alami buah, maka tubuh akan menjadi lebih lambat dalam proses penyerapan gula buah tersebut.

Seperti dikutip dari New York Times dan dikutip pada Rabu (24/2/2016), Dr David Ludwig dari New Balance Foundation Obesity Prevention Center di Boston Children’s Hospital menyebutkan bahwa ketika Anda mengonsumsi makanan atau minuman yang mengandung karbohidrat, sistem pencernaan Anda memecahnya menjadi glukosa, yang kemudian memasuki aliran darah.

Nah, ketika kadar glukosa meningkat, pankreas memproduksi insulin. Insulin ini memberi sinyal agar sel menyerap glukosa sehingga dapat digunakan langsung sebagai energi atau disimpan dalam hati dan otot.

Oleh sebab itu, terlalu banyak makan makanan yang manis dan mengandung gula tinggi disebut-sebut dapat membuat terjadinya lonjakan gula darah dan pankreas pun harus bekerja ekstra. Seiring waktu, risiko diabetes tipe 2 pun meningkat.

Beberapa asupan yang diketahui tinggi karbohidrat dan rendah lemak seperti roti putih, biskuit, dan kue kerap dianggap menjadi biang keladi diabetes jika dikonsumsi berlebihan. Begitu juga dengan minuman manis seperti soda dan jus buah kemasan. “Berbeda dengan buah. Gula alami dalam buah utuh memiliki serat, sehingga tidak akan membuat gula darah melonjak drastis,” tutur Ludwig.

Ya, konsumsi buah memiliki segudang manfaat bagi kesehatan, salah satunya mengurangi risiko kanker payudara. Seperti disampaikan oleh para peneliti dari Harvard T.H Chan School of Public Health dan dipublikasikan dalam jurnal Pediatrics, untuk setiap tambahan 10 gram asupan serat harian, misalnya dari sebuah apel, pada masa dewasa awal, risiko kanker payudara menurun sebesar 13 persen.

big-dancing-banana-smiley-emoticon

INILAHCOM, Jakarta- Hanya makan buah-buahan dan sayuran tidak membantu menurunkan berat badan. Demikian hasil penelitian Universitas Alabama di Birmingham.

“Hanya menambahkan mereka pada urutan teratas makanan yang harus dimakan tidak mungkin menyebabkan perubahan berat badan,” kata pemimpin peneliti Kathryn Kaiser. Tapi Anda masih harus mengkonsumsi buah dan sayuran untuk serat dan kadar vitamin.

Tim peneliti melakukan review sistematis dan meta-analisis data dari lebih 1.200 subjek dalam tujuh acak, percobaan dikontrol untuk mengeksplorasi efek penurunan berat badan dengan meningkatkan konsumsi buah dan sayuran.

Hasilnya hampir semua studi menunjukkan hampir mendekati efek 0 pada penurunan berat badan.

Menurut United States Department of Agriculture’s MyPlate, jumlah konsumsi harian yang disarankan bagi orang dewasa yaitu 1,5-2 cangkir buan dan 2-3 cangkir sayuran. Pola makan yang sering dianjurkan untuk menurunkan berat badan adalah makan buah dan sayuran yang rendah kalori namun mengenyangkan karena kaya serat..

Kaiser mengatakan, dalam konteks keseluruhan dari diet yang sehat, pengurangan energi adalah cara untuk membantu menurunkan berat badan, sehingga untuk mengurangi berat badan orang harus mengurangi asupan kalori.

“Orang-orang membuat asumsi bahwa makanan serat tinggi seperti buah-buahan dan sayuran akan menggantikan makanan yang kurang sehat, dan itu mekanisme untuk menurunkan berat badan, tapi temuan kami dari bukti-bukti terbaik yang tersedia menunjukkan efek yang tampaknya tidak hadir di antara orang hanya diinstruksikan untuk meningkatkan asupan buah dan sayuran,” paparnya lagi.

Melansir nydaily, Sabtu (29/6/2014) penelitian Kaiser terbit dalam American Journal of Clinical Nutrition.

nydaily:
Upping your intake of fruits and veggies won’t help you lose weight, but will give your body plenty of vitamins and nutrients that it needs. Anna Hoychuk/shutterstock.com Upping your intake of fruits and veggies won’t help you lose weight, but will give your body plenty of vitamins and nutrients that it needs.

Researchers at the University of Alabama at Birmingham have found that increasing fruit and vegetable intake does not lead to weight loss, despite decades-old popular belief.

A team of investigators performed a systematic review and meta-analysis of data of more than 1,200 subjects in seven randomized, controlled trials to explore the weight loss effects of increasing fruit and vegetable consumption.

“Across the board, all studies we reviewed showed a near-zero effect on weight loss,” says study leader Kathryn Kaiser, Ph.D., instructor in the UAB School of Public Health. “So I don’t think eating more alone is necessarily an effective approach for weight loss because just adding them on top of whatever foods a person may be eating is not likely to cause weight change.”

According to the United States Department of Agriculture’s MyPlate initiative, the recommended daily serving amount for adults is 1.5-2 cups of fruit and 2-3 cups of vegetables, although dieters are often advised to “fill up” on fruits and vegetables based on the assumption that the low-calorie foods will satiate by taking up space in the digestive tract.

“In the overall context of a healthy diet, energy reduction is the way to help lose weight, so to reduce weight you have to reduce caloric intake,” Kaiser said. “People make the assumption that higher-fiber foods like fruits and vegetables will displace the less healthy foods, and that’s a mechanism to lose weight; but our findings from the best available evidence show that effect doesn’t seem to be present among people simply instructed to increase fruit and vegetable intake.”

Fruits and vegetables provide many vitamins and fiber, so even if they don’t promote weight loss, it seems unlikely they could do harm unless consumed in extreme quantities.

A study comparing the popular Mediterranean diet to a reduced-fat diet says that while the former may not promote weight loss, it significantly reduces risk of type 2 diabetes, significantly more than the latter.

Another study, published last year in the New England Journal of Medicine, worked with patients at risk for cardiac disease, concluding that followers of the Mediterranean diet were 30 percent less likely to experience heart attack or stroke than those on a low-fat diet.

Possibly, though, the attention given to fruits and vegetables casts a shadow over other important dietary foods.

For example, a study published in the International Journal of Obesity found that eating two eggs for breakfast can lead to weight loss, which some might find surprising because eggs are sometimes associated with weight gain.

Kaiser’s study was published in the American Journal of Clinical Nutrition.

Eggs and Cholesterol – How Many Eggs Can You Safely Eat?
February 6, 2014 | by Kris Gunnars | 251,233 views

Woman With Basket of EggsEggs are among the most nutritious foods on the planet.

Just imagine… a whole egg contains all the nutrients needed to turn a single cell into an entire baby chicken.

However, eggs have gotten a bad reputation because the yolks are high in cholesterol.

In fact, a single medium sized egg contains 186 mg of cholesterol, which is 62% of the recommended daily intake.

People believed that if you ate cholesterol, that it would raise cholesterol in the blood and contribute to heart disease.

But it turns out that it isn’t that simple. The more you eat of cholesterol, the less your body produces instead.

Let me explain how that works…
How Your Body Regulates Cholesterol Levels

Eggs in a Basket

Cholesterol is often seen as a negative word.

When we hear it, we automatically start thinking of medication, heart attacks and early death.

But the truth is that cholesterol is a very important part of the body. It is a structural molecule that is an essential part of every single cell membrane.

It is also used to make steroid hormones like testosterone, estrogen and cortisol.

Without cholesterol, we wouldn’t even exist.

Given how incredibly important cholesterol is, the body has evolved elaborate ways to ensure that we always have enough of it available.

Because getting cholesterol from the diet isn’t always an option, the liver actually produces cholesterol.

But when we eat a lot of cholesterol rich foods, the liver starts producing less (1, 2).

So the total amount of cholesterol in the body changes only very little (if at all), it is just coming from the diet instead of from the liver (3, 4).

Bottom Line: The liver produces large amounts of cholesterol. When we eat a lot of eggs (high in cholesterol), the liver produces less instead.

What Happens When People Eat Several Whole Eggs Per Day?

Woman Smiling and Holding a Fried Egg

For many decades, people have been advised to limit their consumption of eggs, or at least of egg yolks (the white is mostly protein and is low in cholesterol).

Common recommendations include a maximum of 2-6 yolks per week. However, there really isn’t much scientific support for these limitations (5).

Luckily, we do have a number of excellent studies that can put our minds at ease.

In these studies, people are split into two groups… one group eats several (1-3) whole eggs per day, the other group eats something else (like egg substitutes) instead. Then the researchers follow the people for a number of weeks/months.

These studies show that:

In almost all cases, HDL (the “good”) cholesterol goes up (6, 7, 8).

Total and LDL cholesterol levels usually don’t change, but sometimes they increase slightly (9, 10, 11, 12).

Eating Omega-3 enriched eggs can lower blood triglycerides, another important risk factor (13, 14).

Blood levels of carotenoid antioxidants like Lutein and Zeaxanthine increase significantly (15, 16, 17).

It appears that the response to whole egg consumption depends on the individual.

In 70% of people, it has no effect on Total or LDL cholesterol. However, in 30% of people (termed “hyper responders”), these numbers do go up slightly (18).

That being said, I don’t think this is a problem. The studies show that eggs change the LDL particles from small, dense LDL to Large LDL (19, 20).

People who have predominantly large LDL particles have a lower risk of heart disease. So even if eggs cause mild increases in Total and LDL cholesterol levels, this is not a cause for concern (21, 22, 23).

The science is clear that up to 3 whole eggs per day are perfectly safe for healthy people who are trying to stay healthy.

Bottom Line: Eggs consistently raise HDL (the “good”) cholesterol. For 70% of people, there is no increase in Total or LDL cholesterol. There may be a mild increase in a benign subtype of LDL in some people.

Eggs and Heart Disease

Egg

Many studies have looked at egg consumption and the risk of heart disease.

All of these studies are so-called observational studies. In studies like these, large groups of people are followed for many years.

Then the researchers use statistical methods to figure out whether certain habits (like diet, smoking or exercise) are linked to either a decreased or increased risk of some disease.

These studies, some of which include hundreds of thousands of people, consistently show that people who eat whole eggs are no more likely to develop heart disease. Some of the studies even show a reduced risk of stroke (24, 25, 26).

However… one thing that is worth noting, is that these studies show that diabetics who eat eggs are at an increased risk of heart disease (27).

Whether the eggs are causing the increased risk in diabetics is not known. These types of studies can only show a correlation and it is possible that the diabetics who eat eggs are, on average, less health conscious than those who don’t.

This may also depend on the rest of the diet. On a low-carb diet (by far the best diet for diabetics), eggs lead to improvements in heart disease risk factors (28, 29).

Bottom Line: Many observational studies show that people who eat eggs don’t have an increased risk of heart disease, but some of the studies do show an increased risk in diabetics.

Eggs Have Plenty of Other Health Benefits Too

Woman smiling and holding an egg

Let’s not forget that eggs are about more than just cholesterol… they’re also loaded with nutrients and have various other impressive benefits:

They’re high in Lutein and Zeaxanthine, antioxidants that reduce your risk of eye diseases like Macular Degeneration and Cataracts (30, 31).

They’re very high in Choline, a brain nutrient that over 90% of people are lacking in (32).

They’re high in quality animal protein, which has many benefits – including increased muscle mass and better bone health (33, 34).

Studies show that eggs increase satiety and help you lose fat (35, 36).

Eggs also taste amazing and are incredibly easy to prepare.

So even IF eggs were to have mild adverse effects on blood cholesterol (which they don’t), the benefits of consuming them would still far outweigh the negatives.

Bottom Line: Eggs are among the most nutritious foods on the planet. They contain important brain nutrients and powerful antioxidants that can protect the eyes.

How Much is Too Much?

Chicken and Egg, Smaller

Unfortunately, we don’t have studies where people are fed more than 3 eggs per day.

It is possible (although unlikely) that eating even more than that could have a detrimental effect on health. Eating more than 3 is uncharted territory, so to speak.

However… I did find an interesting case study (a study with only one individual). It was an 88 year old man who consumed 25 eggs per day.

He had normal cholesterol levels and was in very good health (37).

Of course, a study of one doesn’t prove anything, but it’s interesting nonetheless.

It’s also important to keep in mind that not all eggs are the same. Most eggs at the supermarket are from chickens that are raised in factories and fed grain-based feeds.

The healthiest eggs are Omega-3 enriched eggs, or eggs from hens that are raised on pasture. These eggs are much higher in Omega-3s and important fat-soluble vitamins (38, 39).

Overall, eating eggs is perfectly safe, even if you’re eating up to 3 whole eggs per day.

I personally eat 3-6 whole eggs per day (about 30-40 per week) and my health has never been better.

Given the incredible range of nutrients and powerful health benefits, quality eggs may just be the healthiest food on the planet.

Eggs

Eggs are available year round to provide not only delicious meals on their own but as an essential ingredient for the many baked goods and sauces that would never be the same without them.Composed of a yellow yolk and translucent white surrounded by a protective shell, the incredible nature of the egg is partially found in their unique food chemistry which allows them help in coagulation, foaming, emulsification and browning.

Food Chart

This chart graphically details the %DV that a serving of Eggs provides for each of the nutrients of which it is a good, very good, or excellent source according to our Food Rating System. Additional information about the amount of these nutrients provided by Eggs can be found in the Food Rating System Chart. A link that takes you to the In-Depth Nutritional Profile for Eggs, featuring information over 80 nutrients, can be found under the Food Rating System Chart.

Health Benefits

Eggs are a good source of low-cost high-quality protein, providing 5.5 grams of protein (11.1% of the daily value for protein) in one egg for a caloric cost of only 68 calories. The structure of humans and animals is built on protein. We rely on animal and vegetable protein for our supply of amino acids, and then our bodies rearrange the nitrogen to create the pattern of amino acids we require.

Boost Brain Health with Eggs’ Choline

Another health benefit of eggs is their contribution to the diet as a source of choline. Although our bodies can produce some choline, we cannot make enough to make up for an inadequate supply in our diets, and choline deficiency can also cause deficiency of another B vitamin critically important for health, folic acid.

Choline is definitely a nutrient needed in good supply for good health. Choline is a key component of many fat-containing structures in cell membranes, whose flexibility and integrity depend on adequate supplies of choline. Two fat-like molecules in the brain, phosphatidylcholine and sphingomyelin, account for an unusually high percentage of the brain’s total mass, so choline is particularly important for brain function and health.

In addition, choline is a highly important molecule in a cellular process called methylation. Many important chemical events in the body are made possible by methylation, in which methyl groups are transferred from one place to another. For example, genes in the body can be switched on or turned off in this way, and cells use methylation to send messages back and forth. Choline, which contains three methyl groups, is highly active in this process.

Choline is also a key component of acetylcholine. A neurotrasmitter that carries messages from and to nerves, acetylcholine is the body’s primary chemical means of sending messages between nerves and muscles.

Eggs’ Choline Reduces Inflammation

People whose diets supplied the highest average intake of choline (found in egg yolk and soybeans), and its metabolite betaine (found naturally in vegetables such as beets and spinach), have levels of inflammatory markers at least 20% lower than subjects with the lowest average intakes, report Greek researchers in the American Journal of Clinical Nutrition(Detopoulou P, Panagiotakos DB, et al.)

Compared to those whose diets contained 310 mg of choline daily had, on average:

  • 22% lower concentrations of C-reactive protein
  • 26% lower concentrations of interleukin-6
  • 6% lower concentrations of tumor necrosis factor alpha

Compared to those consuming 360 mg per day of betaine had, on average:

  • 10% lower concentrations of homocysteine
  • 19% lower concentrations of C-reactive protein
  • 12% lower concentrations of tumor necrosis factor alphaEach of these markers of chronic inflammation has been linked to a wide range of conditions including heart disease, osteoporosis, cognitive decline and Alzheimer’s, and type-2 diabetes.In an accompanying editorial in the American Journal of Clinical Nutrition entitled, “Is there a new component of the Mediterranean diet that reduces inflammation?,” Steven Zeisel from the University of North Carolina at Chapel Hill noted that choline and betaine work together in the cellular process of methylation, which is not only responsible for the removal of homocysteine, but is involved in turning off the promoter regions of genes involved in inflammation.”Exposure to oxidative stress is a potent trigger for inflammation. Betaine is formed from choline within the mitochondria , and this oxidation contributes to mitochondrial redox status ,” Zeisel continued.”If the association between choline and betaine and inflammation can be confirmed in studies of other populations, an interesting new dietary approach may be available for reducing chronic diseases associated with inflammation,” he concluded.

    Recommended daily intakes of choline were set in 1998 at 550 milligrams per day for men and 425 milligrams a day for women. No RDI has been set for betaine, which, since it is a metabolite of choline, is not considered an essential nutrient.

    Practical Tip: Egg yolks are the richest source of choline, followed by soybeans. Spinach, beets and whole wheat products are primary sources of betaine. (Olthof MR, van Vliet T, et al. J Nutr)

Eggs — An Easy Answer for Americans’ Unmet Need for Choline

More than 90% of Americans are choline-deficient. An assessment American’s dietary choline intake by Iowa State University researchers (Jensen H, Batres-Marquez S, et al., FASEB Journal) revealed that for older children, men, women and pregnant women, intake is dramatically below Adequate Intake (AI) levels, with only 10% or less of all these groups getting even close to recommended amounts of choline.

This finding is especially concerning in pregnant women because choline is necessary for brain and memory development in the fetus. (Shaw GM, Carmichael SL, Am J Epidemiol; Zeisel SH, Annu Rev Nutr) The National Academy of Sciences recommends higher daily intake of choline for pregnant and breastfeeding women (550 mg and 450 mg, respectively).

Older adults are also at high risk of choline deficiency. Research presented by Debra Keast, PhD, at the 31st National Nutrient Data Bank Conference, Washington, DC, revealed that choline intake decreases with age, with adults ages 71 and older typically consuming an average of about 264 milligrams per day, roughly half the AI for choline (550 mg/day for men, 425 mg/day for women).

And even getting the recommended AI for choline may not meet the needs of approximately 20% of men. Research published in the American Journal of Clinical Nutrition (Fischer LM, deCosta KA, et al.) found that when 26 men were given a diet providing 550 mg/day of choline, 6 of the men developed fatty liver or muscle damage (signs of choline insufficiency).

In addition to the 26 men, 16 premenopausal and 15 postmenopausal women took part in this study. All participants were fed a diet supplying 550 mg/day of choline for 10 days followed by a diet containing less than 50 mg/day of choline for up to another 42 days.

When deprived of dietary choline, 77% of the men, 80% of the postmenopausal women, and 44% of the premenopausal women developed fatty liver or muscle damage. (Premenopausal women, while harmed, were not as sorely affected because choline can be made by our bodies from the de novo synthesis of phosphatidylcholine, which is up-regulated by estrogen.)

Practical Tip: Foods that are good sources of choline should be frequent contributors to your healthy way of eating. Two large eggs provide 252 milligrams of choline (all in yolk), a little less than half the recommended daily supply, and and also contain 630 milligrams (yes, milligrams not micrograms) ofphosphatidylcholine. Although most sources just report the free choline at 252 micrograms, it is the phosphatidylcholine that is the most common form in which choline is incorporated into cell membrane phospholipids.

Other rich sources of choline (per 100 grams / 3 ounces of food) include beef liver (355 mg), dried soy beans (116 mg), wheat germ (152 mg), cod (83 mg), chicken (70 mg, and salmon (65 mg).

An Egg Breakfast Helps Promote Weight Loss

In a randomized controlled trial, 160 overweight or obese men and women were divided into 2 groups, one of which ate a breakfast including 2 eggs, while the other consumed a bagel breakfast supplying the same amount of calories and weight mass (an important control factor in satiety and weight loss studies). Participants ate their assigned breakfast at least 5 days a week for 8 weeks as part of a low-fat diet with a 1,000 calorie deficit. (Dhurandhar N, Vander Wal J, et al, FASEB Journal)

Compared to those on the bagel breakfast, egg eaters:

  • Lost almost twice as much weight — egg eaters lost an average of 6.0 pounds compared to bagel eaters’ 3.5 pound loss.
  • Had an 83% greater decrease in waist circumference
  • Reported greater improvements in energy

No significant differences were seen between blood levels of total, HDL and LDL cholesterol, and triglycerides in either group, confirming what other studies (Ballesteros MN, Cabrera RM, Am J Clin Nutr) have shown, including a relative risk study presented at the Experimental Biology meeting: healthy people can safely enjoy eggs without increasing their heart attack risk. The relative risk study, a thorough scientific review of the major studies concerning heart disease causation, which was conducted by Washington, DC-based scientific consulting firm, Exponent, found that eggs contribute just 0.6 percent of men’s and 0.4 percent of women’s coronary heart disease risk.

Eggs and Heart Health

In addition to its significant effects on brain function and the nervous system, choline also has an impact on cardiovascular health since it is one of the B vitamins that helps converthomocysteine, a molecule that can damage blood vessels, into other benign substances. Eggs are also a good source of vitamin B12, another B vitamin that is of major importance in the process of converting homocysteine into safe molecules.

Eggs are high in cholesterol, and health experts in the past counseled people to therefore avoid this food. (All of the cholesterol in the egg is in the yolk.) However, nutrition experts have now determined people on a low-fat diet can eat one or two eggs a day without measurable changes in their blood cholesterol levels. This information is supported by a statistical analysis of 224 dietary studies carried out over the past 25 years that investigated the relationship between diet and blood cholesterol levels in over 8,000 subjects. What investigators in this study found was that saturated fat in the diet, not dietary cholesterol, is what influences blood cholesterol levels the most.

Improve Your Cholesterol Profile

Not only have studies shown that eggs do not significantly affect cholesterol levels in most individuals, but the latest research suggests that eating whole eggs may actually result in significant improvement in one’s blood lipids (cholesterol) profile-even in persons whose cholesterol levels rise when eating cholesterol-rich foods.

In northern Mexico, an area in which the diet contains a high amount of fat because of its reliance on low-cost meat products and tortillas made with hydrogenated oils, coronary artery disease is common. In a study published in the American Journal of Clinical Nutrition, researchers evaluated the effects of daily consumption of whole eggs on the ratio of LDL (bad) cholesterol to HDL (good) cholesterol, and phenotype (the way an individual’s genetic possibilities are actually expressed) in 54 children (8-12 years old) from this region. A month of eating 2 eggs daily, not only did not worsen the children’s ratio of LDL:HDL, which remained the same, but the size of their LDL cholesterol increased-a very beneficial change since larger LDL is much less atherogenic (likely to promote atherosclerosis) than the smaller LDL subfractions. Among children who originally had the high-risk LDL phenotype B, 15% shifted to the low-risk LDL phenotype A after just one month of eating whole eggs.

Helping to Prevent Blood Clots

Eating eggs may help lower risk of a heart attack or stroke by helping to prevent blood clots. A study published in Biological and Pharmaceutical Bulletin demonstrated that proteins in egg yolk are not only potent inhibitors of human platelet aggregation, but also prolong the time it takes for fibrinogen, a protein present in blood, to be converted into fibrin. Fibrin serves as the scaffolding upon which clumps of platelets along with red and white blood cells are deposited to form a blood clot. These anti-clotting egg yolk proteins inhibit clot formation in a dose-dependent manner-the more egg yolks eaten, the more clot preventing action.(That being said, it’s still important to only eat the amount of eggs that fits within your own personal Healthiest Way of Eating.)

Protection against Age-Related Macular Degeneration and Cataracts

Lutein, a carotenoid thought to help prevent age-related macular degeneration and cataracts, may be found in even higher amounts in eggs than in green vegetables such as spinach, which have been considered its major dietary sources, as well as in supplements. Research presented at the annual American Dietetic Association Conference in San Antonio, Texas, in 2003, by Elizabeth Johnson from the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University also showed that natural lutein esters found in eggs are as or even more bioavailable as the forms of the nutrient offered in purified lutein products. Johnson’s trial tested serum lutein concentration in 10 healthy men, before and after daily consumption of 6mg lutein obtained from four different sources: eggs from chickens fed marigold petals (which are high in lutein), spinach (one of the best known sources of dietary lutein), lutein ester supplements (purified lutein) and lutein supplements. Differences in serum lutein levels in response to the various types of doses were observed the day after the first dose: the serum lutein response to egg was significantly greater than the supplements but no higher than the response to the spinach. After nine days of daily lutein dosing, the serum lutein response was significantly greater in the egg phase than either of the supplements or the spinach. The bottom line: this study suggests that eating lutein-rich foods may be a more effective means of boosting lutein concentration in the eye than taking supplements.

Another human study, published in the i>Journal of Nutrition, confirms that lutein is best absorbed from egg yolk-not lutein supplements or even spinach. Egg yolks, although they contain significantly less lutein than spinach, are a much more bioavailable source whose consumption increases lutein concentrations in the blood many-fold higher than spinach.

Although the mechanism by which egg yolk increases lutein bioavailability is not yet known, it is likely due to the fats (cholesterol and choline) found in egg yolk. Lutein, like other carotenoids, is fat-soluble, so cannot be absorbed unless fat is also present. (If this is the case, then to enhance the lutein absorption from spinach and other vegetables rich in this nutrient, we suggest enjoying them with some fat such as extra virgin olive oil). To maximally boost your lutein absorption, you could also combine both eggs and spinach. Whether you prefer your spinach steamed, sautéed or fresh in spinach salad, dress it with a little olive oil and a topping of chopped hard-boiled egg. For a flavorful, quick and easy recipe featuring eggs and spinach, try our Poached Eggs over Spinach and Mushrooms.

Eggs Protect Eyesight without Increasing Cholesterol

Two new studies published in the Journal of Nutrition add further evidence to the theory that a daily egg-whose yolk is a rich source of vision-protective carotenoids, including not only lutein but also zeaxanthin-may reduce the risk of developing age-related macular degeneration (AMD).

The studies, both conducted at the University of Massachusetts, show that, in addition to keeping hunger at bay longer (eggs’ satiety index is 50% than that of most breakfast cereals), an egg a day boosts blood levels of both lutein and zeaxanthin, thus reducing the risk of AMD-without increasing cholesterol or triglyceride levels.

In AMD, the macula, the central part of the retina which controls fine vision, deteriorates, greatly limiting eyesight or even resulting in blindness in those afflicted. The leading cause of blindness in people over age 50, AMD afflicts more than 10 million people in the United States, plus an additional 15 to 20 million worldwide.

In the first study, a randomized cross-over trial, Elizabeth Goodrow and her team investigated the effects of eating one egg a day on blood levels of lutein, zeaxanthin, cholesterol and triglycerides in 33 men and women over age 60.

After a no-egg start up week, volunteers ate either an egg or egg substitute daily for 5 weeks, then again ate no eggs for a week before crossing over to the other intervention for a second 5 weeks.

After the 5-week period in which they ate a daily egg, participants’ blood levels of lutein and zeaxanthin significantly increased by 26 and 38%, respectively, compared to their levels of these carotenoids after their no-egg week.

And although eggs are well-known for containing cholesterol, participants’ blood levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were not affected by eating an egg a day.

In the second study, researchers led by Adam Wenzel looked at the effect of a 12-week egg intervention on lutein and zeaxanthin levels in both the blood and the retina of the eye (the macular pigment optical density or MOPD) of 24 women ranging in age from 24 to 59.

The women were randomly assigned to eat 6 eggs every week containing either 331 micrograms (Egg1) or 964 micrograms (Egg2) of lutein and zeaxanthin per yolk, or a placebo (a sugar-filled pill).

No changes in cholesterol levels were seen in the women eating eggs, but in those given the placebo (the sugar pill), increases in total cholesterol and triglycerides were recorded.

Unlike the first study, only blood levels of zeaxanthin, but not lutein, increased in both Egg1 and Egg2 groups; however, carotenoid levels in the retina (MPOD) increased in both egg intervention groups, a result that suggests a daily egg offers protection against AMD.

Although egg yolk contains less lutein and zeaxanthin than some other foods-spinach, for example-when supplied by eggs, these carotenoids appear to be especially well absorbed into the retina. “Increasing egg consumption to 6 eggs per week may be an effective method to increase MPOD,” wrote lead study author Wenzel.

So, enjoy a quick and easy, vision-sustaining poached or soft boiled egg for breakfast. Take an egg salad sandwich to work or add a hard boiled egg to your luncheon salad. On the weekend, treat yourself to our Healthy Breakfast Frittata or Egg Crepes filled with veggies, one of the delicious egg recipes featured inThe World’s Healthiest Foods Essential Guide. We suggest choosing organic omega-3-rich eggs if available. Produced by hens fed a diet rich in flaxseed, these eggs are an exceptional source not only of lutein and xeaxanthin, but anti-inflammatory omega-3 essential fatty acids as well.

Description

Eggs are egg-ceptional foods. They are whole foods, prepackaged sources of carbohydrates, protein, fat and micronutrients. Yet, their eggs-quisite nutritional value should not be surprising when you remember that an egg contains everything needed for the nourishment of a developing chick.

Eggs are composed of a yellow yolk and translucent white surrounded by a protective shell that can be white or brown, depending upon the breed of the chicken. The shell’s color is not related to the quality or nutritional value of the egg itself.

In addition to their wonderful taste and nutritional content, eggs hold an esteemed place in cooking since due to their food chemistry, they serve many unique functions in recipes, including coagulation, foaming, emulsification and browning.

While chickens are not the only animals that lay eggs that are enjoyed in various cuisines, it is the type featured in this article because it is the most highly accessible in North America.

In Latin, the scientific name for chicken is Gallus domesticus.

History

The history of the egg as food runs mostly parallel with the history of people consuming chicken as food. Although it is uncertain when and where it began, the practice of raising chickens for food is ancient and so, subsequently, is the consumption of eggs as food, extending back to the times of early man.

Eggs have always been a symbol of fertility and have been an icon of religious worship. To this day, there is still a lot of folklore surrounding eggs that is enjoyed by different cultures around the world.

One of the most widely held food and holiday associations is that of the Easter egg. How the egg became associated with this holiday seems to have roots that are both biological and cultural. Before more modern techniques of poultry raising, hens laid few eggs during the winter. This meant that Easter, occuring with the advent of spring, coincided with the hen’s renewed cycle of laying numerous eggs. Additionally, since eggs were traditionally considered a food of luxury, they were forbidden during Lent, so Christians had to wait until Easter to eat them-another reason eggs became associated with this holiday. Interestingly enough, the custom of painting eggshells has an extensive history and was a popular custom among many ancient civilizations, including the Egyptians, Chinese, Greeks and Persians.

How to Select and Store

Oftentimes, in the U.S., eggs are classified according to the USDA grading system and bear a label of AA, A, or B. This grading is an indicator of quality parameters, including freshness, with AA being of the most superior in quality. Eggs are also labeled according to their size-extra large, large, medium and small-which is graded according to a standard.

Yet, you may not see any labeling on the eggs you buy since it is not legally mandatory that they be inspected and graded by these federal standards. This is often the situation when you buy farm fresh eggs from a local purveyor. If this is the case, get to know the seller and his or her reputation and make sure that, as usual, the eggs are kept refrigerated.

Inspect any eggs that you purchase for breaks or cracks. And of course, take care when packing them in your shopping bag for the trip home as they are very fragile.

Store eggs in the refrigerator where they will stay fresh for about one month. Do not wash them as this can remove their protective coating. Keep them in their original carton or in a covered container so that they do not absorb odors or lose any moisture. Do not store them in the refrigerator door since this exposes them to too much heat each time the refrigerator is opened and closed. Make sure to store them with their pointed end facing downward as this will help to prevent the air chamber, and the yolk, from being displaced.

How to Enjoy

For some of our favorite recipes, click Recipes.

Tips for Preparing Eggs:

In order to prevent any possible contamination to a recipe by a spoiled egg, break each egg separately into a small bowl before combining with the other ingredients.

A Few Quick Serving Ideas:

Hard-boiled eggs are fun to eat and easy to pack for on-the-go lunches.

Mix chopped up hard-boiled eggs with fresh lemon juice and olive oil, leeks and dill (and salt and pepper to taste) to make a healthy egg salad.

Instead of Eggs Benedict, make Eggs “Buenodict.” Place a poached egg on top of a whole grain English muffin lined with steamed spinach. Top with salsa or any of your favorite seasonings and enjoy.

Say olé to the day with a huevos ranchero breakfast. Add chili peppers to scrambled eggs and serve with black beans and corn tortillas.

Individual Concerns

Allergic Reactions to Eggs

Although allergic reactions can occur to virtually any food, research studies on food allergy consistently report more problems with some foods than with others. For example, according to a recent report by the U.S. Centers for Disease Control, 90% of food allergies are associated with 8 food types: hen’s eggs, fish, crustacean shellfish, cow’s milk, soy foods, peanuts, wheat, and tree nuts. (Crustacean shellfish include shrimp, prawns, lobster, and crab. Tree nuts include almonds, cashews, walnuts, pecans, pistachios, Brazil nuts, hazelnuts, and chestnuts.)

These foods do not need to be eaten in their pure, isolated form in order to trigger an adverse reaction. For example, yogurt made from cow’s milk is also a common allergenic food, even though the cow’s milk has been processed and fermented in order to make the yogurt. Ice cream made from cow’s milk would be an equally good example.

Food allergy symptoms may sometimes be immediate and specific, and can include skin rash, hives, itching, and eczema; swelling of the lips, tongue, or throat; tingling in the mouth; wheezing or nasal congestion; trouble breathing; and dizziness or lightheadedness. But food allergy symptoms may also be much more general and delayed, and can include fatigue, depression, chronic headache, chronic bowel problems (such as diarrhea or constipation), and insomnia. Because most food allergy symptoms can be caused by a variety of other health problems, it is good practice to seek the help of a healthcare provider when evaluating the role of food allergies in your health.

Handling of Eggs

Health safety concerns about eggs center on salmonellosis(salmonella-caused food poisoning). Salmonella bacteria from the chicken’s intestines may be found even in clean, uncracked eggs. Formerly, these bacteria were found only in eggs with cracked shells. Safe food techniques, like washing the eggs before cracking them, may not protect you from infection. To destroy the bacteria, eggs must be cooked at high enough temperatures for a sufficient length of time to destroy the bacteria. Soft-cooked, sunny-side up or raw eggs carry salmonellosis risk. Hard-boiled, scrambled, or poached eggs do not.

Another reason to avoid consuming raw eggs is that raw egg whites contain a glycoprotein called avidin, which binds to eggs’ supply of the B vitamin biotin very tightly, preventing its absorption. Cooking the egg whites changes avidin, making it susceptible to digestion and unable to interfere with the intestinal absorption of biotin.

Dishes and utensils used when preparing eggs should be washed in warm water separately from other kitchenware, and hand-washing with warm, soapy water is essential after handling eggs. Any surfaces that might have potentially come into contact with raw egg should be washed and can be sanitized with a solution of 1 teaspoon chlorine to 1 quart water.

Nutritional Profile

Our food ranking system also qualified eggs as a very good source of selenium, iodine, and vitamin B2 and a good source of protein, molybdenum, phosphorus, vitamin B5, vitamin B12 and vitamin D.

For an in-depth nutritional profile click here: Eggs.

In-Depth Nutritional Profile

In addition to the nutrients highlighted in our ratings chart, an in-depth nutritional profile for Eggs is also available. This profile includes information on a full array of nutrients, including carbohydrates, sugar, soluble and insoluble fiber, sodium, vitamins, minerals, fatty acids, amino acids and more.

Introduction to Food Rating System Chart

In order to better help you identify foods that feature a high concentration of nutrients for the calories they contain, we created a Food Rating System. This system allows us to highlight the foods that are especially rich in particular nutrients. The following chart shows the nutrients for which this food is either an excellent, very good, or good source (below the chart you will find a table that explains these qualifications). If a nutrient is not listed in the chart, it does not necessarily mean that the food doesn’t contain it. It simply means that the nutrient is not provided in a sufficient amount or concentration to meet our rating criteria. (To view this food’s in-depth nutritional profile that includes values for dozens of nutrients – not just the ones rated as excellent, very good, or good – please use the link below the chart.) To read this chart accurately, you’ll need to glance up in the top left corner where you will find the name of the food and the serving size we used to calculate the food’s nutrient composition. This serving size will tell you how much of the food you need to eat to obtain the amount of nutrients found in the chart. Now, returning to the chart itself, you can look next to the nutrient name in order to find the nutrient amount it offers, the percent Daily Value (DV%) that this amount represents, the nutrient density that we calculated for this food and nutrient, and the rating we established in our rating system. For most of our nutrient ratings, we adopted the government standards for food labeling that are found in the U.S. Food and Drug Administration’s “Reference Values for Nutrition Labeling.” Read more background information and details of our rating system.

Egg, whole, boiled

1.00 each

44.00 grams

68.20 calories

Nutrient Amount DV

(%)

Nutrient

Density

World’s Healthiest

Foods Rating

tryptophan 0.07 g 21.9 5.8 very good
selenium 13.55 mcg 19.4 5.1 very good
iodine 23.76 mcg 15.8 4.2 very good
vitamin B2 (riboflavin) 0.23 mg 13.5 3.6 very good
protein 5.54 g 11.1 2.9 good
molybdenum 7.48 mcg 10.0 2.6 good
vitamin B12 (cobalamin) 0.49 mcg 8.2 2.2 good
phosphorus 75.68 mg 7.6 2.0 good
vitamin B5 (pantothenic acid) 0.62 mg 6.2 1.6 good
vitamin D 22.88 IU 5.7 1.5 good
World’s Healthiest

Foods Rating

Rule
excellent DV>=75% OR Density>=7.6 AND DV>=10%
very good DV>=50% OR Density>=3.4 AND DV>=5%
good DV>=25% OR Density>=1.5 AND DV>=2.5%

In-Depth Nutritional Profile for Eggs

teori penunjang lage :

 

The process by which food is converted into useful energy is called metabolism . It begins with chemical processes in the gastrointestinal tract which change plant and animal food into less complex components so that they can be absorbed to fulfill their various functions in the body— growth, repair, and fuel. Different foods have different energy values, measured in calories. An ideal diet for the average healthy individual provides the highest nutritional benefits from the fewest number of calories. Information on the protein, fat, and carbohydrate content in specific foods, as well as the number of calories, may be obtained by consulting the tables “Nutrients in Common Foods.” The Metric Equivalents table converts spoon and cup measures into metric measures.

Protein

Of the several essential components of food, protein is in many ways the most important. This is so not only because it is one of the three principal sources of energy, but also because much of the body’s structure is made up of proteins. For example, the typical 160-pound man is composed of about 100 pounds of water, 29 pounds of protein, 25 pounds of fat, 5 pounds of minerals, 1 pound of carbohydrate, and less than an ounce of vitamins. Because the muscles, heart, brain, lungs, and gastrointestinal organs are made up largely of protein, and since the protein in these organs is in constant need of replacement, its importance is obvious.

The recommended dietary allowance for protein is 0.8 g/Kg of body weight per day for persons aged 15 and up and 1 g/Kg of body weight for children under 15. (To convert your weight from pounds to kilograms, divide by 2.2. Thus a woman weighing 130 pounds weighs about 59 kilograms and needs about 47 grams of protein a day. A man weighing 175 pounds needs about 64 grams of protein a day.) Most Americans, however, eat about twice the amount they need, and while more may sound better, too much is too much. Your body uses what it needs. Some excess protein is excreted as urine; the rest is converted to fat.

Chemically, proteins are varying mixtures of amino acids that contain various elements, including nitrogen. There are 22 different amino acids that are essential for the body’s protein needs. Nine of these must be provided in the diet and are thus called essential amino acids; the rest can be synthesized by the body itself.

Meat, fish, poultry, eggs, and milk or milk products are the primary protein foods and contain all of the necessary amino acids; they are therefore called complete proteins. Grains and vegetables are partly made up of protein, but more often than not, they do not provide the whole range of amino acids required for proper nourishment. When properly combined, however, vegetable proteins, too, can be complete. For example, mixing rice and dried beans provides the same quality of protein as a steak (with a lot less fat).

One gram of protein provides four calories of energy.

Carbohydrates

Carbohydrates are another essential energy source. Called starches or sugars , they are present in large quantities in grains, fruits, and nuts. As complex carbohydrates , or polysaccharides , they are found in the foods named and particularly in breads, breakfast cereals, flours, pastas, barley legumes, rice, and starchy vegetables. Simple carbohydrates , or mono- or disaccharides, are found in such foods as table sugars, candy, pastries, and soft drinks.

Complex carbohydrates are primary sources of calories, nutrients, and fiber—for such purposes as muscle contraction, weight reduction, and control of sodium and cholesterol. Simple carbohydrates, on the other hand, are pure sources of calories and contain little nutritional value. It is for this reason that they are often termed “empty” calories. Lack of adequate carbohydrates means the body will begin to convert body fat or protein into sugar.

Although there is no absolute dietary requirement for carbohydrates, it is generally recommended that more than half the energy requirement beyond infancy be provided by complex carbohydrates. One gram of carbohydrate provides four calories of energy. Thus the average man consuming about 2,900 calories per day should consume about 360 grams of carbohydrate. The average woman consuming about 2,200 calories per day should consume about 275 grams of carbohydrate.

Fats

Fats are a chemically complex food component composed of glycerol (a sweet, oily alcohol) and fatty acids. Fats exist in several forms and come from a variety of sources. One way to think of them is to group them as visible fats, such as butter, salad oil, or the fat seen in meat, and as invisible fats, which are mingled, blended, or absorbed into food, either naturally, as in nuts, meat, or fish, or during cooking. Another way is to think of them as solid at room temperature (fats), or as liquid at room temperature (oils).

Saturated and Unsaturated

Fats are also classified as saturated or unsaturated . This is a chemical distinction based on the differences in molecular structure of different kinds of fat. If the carbon atoms in a fat molecule are surrounded or boxed in by hydrogen atoms, they are said to be saturated. This type of fat tends to be solid at room temperature, and high consumption of it increases the cholesterol content of the blood, which can lead to heart disease. Unsaturated fats, such as those found in fish and vegetable oils, contain the least number of hydrogen atoms and do not add to the blood cholesterol content. They are either monounsaturated or polyunsaturated . In general, fats in foods of plant origin are more unsaturated than in those of animal origin (except for coconut and palm oils, which are highly saturated). It is recommended that you consume no more than 30 percent of your daily calories from fats; 10 percent of each of the three types, or, for our average man, about 32 grams total; for our average woman, about 24 grams total.

Fats play several essential roles in the metabolic process. First of all, they provide more than twice the number of calories on a comparative weight basis than do proteins and carbohydrates (one gram of fat contains nine calories). They also can be stored in the body in large quantities (in adipose tissue) and used as a later energy source. They serve as carriers of the fat-soluble vitamins A, D, E, and K, and—of no little importance—they add to the tastiness of food.

Vitamins

Vitamins , which are present in minute quantities in foods in their natural state, are essential for normal metabolism and for the development and maintenance of tissue structure and function. In addition to the fat-soluble vitamins noted above, there are a number of B vitamins, as well as vitamin C, also called ascorbic acid . If any particular vitamin is missing from the diet over a sufficiently long time, a specific disease will result.

Vitamin A

Vitamin A is essential for vision, growth, cell growth and development, reproduction, a strong immune

 

Average Daily Calorie Consumption

 

 

Calorie Consumption for Some Activities

 

 

Modified Calorie/Weight Reduction Diet

 

Average Daily Calorie Consumption
Men Calories
Guidelines for average daily calorie consumption by men and women. With increasing use of labor-saving devices, most Americans fall into the sedentary category.
Sedentary 2,500
Moderately active 3,000
Active 3,500
Very active 4,250
Women Calories
Sedentary 2,100
Moderately active 2,500
Active 3,000
Very active 3,750
Calorie Consumption for Some Activities
Type of Activity Calories Per Hour
Sedentary: reading, sewing, typing, etc. 30–100
Light: cooking, slow walking, dressing, etc. 100–170
Moderate: sweeping, light gardening, making beds, etc. 170–250
Vigorous: fast walking, hanging out clothes, golfing, etc. 250–350
Strenuous: swimming, bicycling, dancing, etc. 350 and more
Modified Calorie/Weight Reduction Diet
Sample Menus
1,500 Calories 1,800 Calories 2,000 Calories
From the Clinical Center Diet Manual , Clinical Center Nutrition Department, National Institutes of Health, Department of Health and Human Services.
Breakfast 1 serving fruit/juice 1 serving fruit/juice 1 serving fruit/juice
1 slice toast 1 slice toast 1 slice toast
1 serving egg or substitute 1 serving egg or substitute 1 serving egg or substitute
1 serving margarine 1 serving cereal 1 serving cereal
1 cup skim milk 1 serving margarine 1 serving margarine
coffee/tea 1 cup skim milk 1 cup skim milk
coffee/tea coffee/tea
Lunch 2-3 ounces meat 2-3 ounces meat 2-3 ounces meat
1 serving potato or 1 serving potato or 1 serving potato or
substitute substitute substitute
1 serving bread 1 serving bread 1 serving bread
vegetables vegetables vegetables
salad/non-fat dressing salad/non-fat dressing Salad/non-fat dressing
2 servings fruit/juice
2 servings fruit 2 servings fruit/juice 1 serving margarine
1 serving margarine 1 serving margarine 1 cup skim milk
coffee/tea coffee/tea coffee/tea
Dinner 2-3 ounces meat 2-3 ounces meat 2-3 ounces meat
1 serving potato or substitute 1 serving potato or substitute 2 servings potato or substitute
1 serving bread 1 serving bread 1 serving bread
vegetables vegetables vegetables
salad/non-fat dressing salad/non-fat dressing Salad/non-fat dressing
1 serving fruit/juice
1 serving fruit 2 servings fruit/juice 2 servings margarine
2 servings margarine 2 servings margarine coffee/tea
coffee/tea coffee/tea
Snack 3 graham crackers 1 ounce meat 1 ounce meat
1 cup skim milk 1 slice bread 1 slice bread
1 serving reduced-fat mayonnaise 1 serving reduced-fat mayonnaise
1 cup skim milk non-alcoholic beverage

system, and healthy hair, skin, and mucous membranes.

Vitamin A is fat soluble and is therefore stored by the body (in the liver). It comes in two forms: retinol, found only in animal foods (chiefly liver), and beta-carotene, found in fruits and vegetables (chiefly deep green or orange ones like spinach and sweet potatoes). Retinol is instantly available for bodily use, while beta-carotene must be converted by the body into retinol before it can be used. (Because the body will not convert excess beta-carotene into retinol, there is no danger of overdosing on this form of vitamin A Retinol, however, can be extremely toxic at high levels.)

Symptoms of vitamin A deficiency include dry rough skin, slow growth, night blindness, thickening of bone, and increased susceptibility to infection. Vitamin A deficiency is rare in the United States.

Formerly measured in International Units (IU), vitamin A content is now expressed retinol equivalents (RE). One RE equals 10 IU of beta-carotene and 3.33 IU of retinol. The Recommended Daily Allowance (RDA) for vitamin A for adult males is 1000 RE and for adult women, 800 RE.

Vitamin D

Vitamin D is essential for proper metabolism of calcium, which is primarily responsible for the healthy growth of bones and teeth.

Vitamin D is fat soluble and therefore excessive intake can be toxic. It is consumed chiefly as an addition to milk and is also manufactured by the body by a reaction of sunlight on sterols present in the skin.

The major deficiency disease of vitamin D in children is rickets (deformation of the skeleton) and in adults excessive bone loss and fractures.

The RDA for adults over 24 is 5 mi-crograms.

Vitamin E (tocopherol)

Vitamin E is essential for healthy nerve function and reproduction.

Vitamin E is found principally in plant oils, particularly wheat germ oil and nuts. It is fat soluble, but there is little danger of toxicity because absorption by the body is relatively inefficient.

Vitamin E is measured in tocopherol equivalents (TE). The RDA for adult males is 10 TE and for adult women 8 TE. Deficiencies in a normal diet are rare.

Vitamin K

Vitamin K is essential for proper clotting of the blood.

Vitamin K is fat soluble and is found primarily in green leafy vegetables. Another form of the compound is synthesized by intestinal bacteria. Like vitamin E, there is little danger from ingesting too much vitamin K, and most diets provide an adequate supply.

The RDA for adult males over age 24 is 80 micrograms and for adult women 65 micrograms.

Vitamin C (ascorbic acid)

Vitamin C is essential for healthy skin, bones, teeth, and muscles, for producing and maintaining collagen, and for fighting infection.

Vitamin C is water soluble and therefore must be ingested every day. It is widely available in a variety of colorful fruits and vegetables, such as peppers, broccoli, cabbage, oranges, strawberries, and tomatoes. Unfortunately, vitamin C is also the most unstable of all vitamins and minerals: it is easily destroyed by heat and oxygen, and thus care should be taken in cooking and storing of fruits and vegetables.

The classic vitamin C deficiency disease is scurvy, typified by the wasting away of muscles, wounds and bruises that don’t heal, and bleeding, deteriorating gums. Milder forms of vitamin C deficiency produce milder versions of these symptoms. Vitamin C deficiency has also been linked to such health problems as the common cold, anemia, atherosclerosis, asthma, cancer of the stomach and esophagus, infertility in males, rheumatoid arthritis, and cataracts.

Vitamin C is measured in milligrams (mg). The RDA for adults is 60 mg. Megadoses of vitamin C are often recommended to fight colds or as a general preventive measure against disease, although the body only uses as much as it needs; the rest is excreted in the urine. Toxicity is rarely a problem.

Thiamin (vitamin B 1 )

Thiamin is essential for the proper metabolism of carbohydrates and for a healthy nervous system.

Thiamin is water soluble and is found primarily in cereals, wheat germ, port, and nuts. It is strongly susceptible to destruction during cooking. Deficiency is not common among the general population, but studies have shown heavy drinkers, pregnant women, and the elderly to be more deficient. Severe thiamin deficiency results in beriberi, a disease that weakens the body, disables the mind, and permanently damages the heart. Symptoms of deficiency include loss of appetite, nausea, vomiting, constipation, depression, fatigue, poor eye-hand coordination, irritability, headaches, and anxiety.

Thiamin is measured in milligrams. The RDA for adult males is 1.5 mg and for adult women 1.1 mg. Danger of toxicity is rare as excess thiamin is excreted in urine.

Riboflavin (vitamin B 2 )

Riboflavin is essential for growth and repair of tissues and aids in DNA synthesis. It helps metabolize proteins, fats, and carbohydrates.

Most Americans get plenty of this water-soluble vitamin, which is readily found in liver, eggs, and milk products. Studies have found that children in low-income families, however, are less likely to get enough riboflavin. Signs of deficiency include a purplish-colored tongue; cracks at the corners of the mouth; sores and burning of the lips, mouth, and tongue; itchy inflamed eyelids; flaky skin around the nose, ears, eyebrows, or hairline; and light sensitivity of eyes. Deficiency in riboflavin often means deficiency in other B vitamins as well. Cataracts, birth defects, and anemia have been linked to riboflavin deficiency.

Unlike vitamin C and thiamin, riboflavin is not easily destroyed by cooking, although adding baking soda to vegetables when cooking creates an alkaline solution that destroys it. Risk of toxicity is very low, and excess riboflavin is excreted in the urine.

Riboflavin is measured in milligrams. The RDA for adult males is 1.7 mg and for adult women 1.3 mg.

Niacin (vitamin B 3 )

Niacin is essential for the release of energy from carbohydrates, fats, and proteins and for the formation of DNA.

Most Americans get plenty of niacin from their diets; only heavy drinkers are at risk of deficiency. Severe deficiencies of niacin result in pellagra, a disease virtually wiped out in the United States since the 1930s with the advent of fortified flour and cereals with the vitamin.

Niacin is widely available in a variety of plant and animal foods, including fish, liver, turkey, cereals, and peanuts. The body is also able to convert the amino acid tryptophan into niacin, and thus proteins high in tryptophan also provide plenty of niacin.

Niacin in measure in milligrams (60 mg of tryptophan equal 1 mg of niacin). The RDA for adult males is 19 mg. and for women 15 mg.

Vitamin B 6

Vitamin B 6 is essential for fat and carbohydrate metabolism and for the formation and breakdown of amino acids. It also helps regulate blood glucose levels and is needed to synthesize hemoglobin.

Vitamin B 6 occurs in three forms: pyridoxine, pyridoxal, and pyridoxam-ine, which are converted by the body into pyridoxal phosphate and pyridox-amine phosphate. It is most readily found in nuts, kidney, liver, eggs, pork, poultry, dried fruits, and fish.

Although few Americans get the full RDA of vitamin B 6 , there is no evidence of corresponding overt deficiency symptoms. The following health problems, however, have been linked to B 6 deficiency: asthma, carpal tunnel syndrome, cancer (melanoma, breast, and bladder), diabetes, coronary heart disease, premenstrual syndrome, sickle-cell anemia, and aging and dementia.

In moderate doses B 6 is not toxic. Although excessive amounts of this water-soluble vitamin are to a great extent flushed out of the body in the urine, high doses have produced neurological disturbances such as numbness in the hands, feet, and mouth.

Vitamin B 6 is measured in milligrams. The RDA for adult men is 2 mg and for women 1.6 mg.

 

Recommended Dietary Allowances for Fat-Soluble Vitamins

 

Recommended Dietary Allowances for Fat-Soluble Vitamins
Vit. A Vit. D Vit. E Vit. K
Age (meg RE) (meg) (mgTE) (meg)
Infants 0 to .5 375 7.5 3 5
.5 to 1 10 4 10
Children 1 to 3 400 6 15
4 to 6 500 7 20
7 to 10 700 30
Males 11 to 14 1,000 10 45
15 to 18 65
19 to 24 70
25 to 50 5 80
51 +
Females 11 to 14 800 10 8 45
15 to 18 55
19 to 24 60
25 to 50 5 65
51 +
Pregnant 10 10
Nursing 1st 6 months 1,300 12
2nd 6 months 1,200 11

Vitamin B 12

Vitamin B 12 is important for normal growth, healthy nerve tissue, and normal blood formation.

Most Americans get plenty of B 12 . It is found chiefly in animal foods: meat, fish, eggs, and milk products. Only strict vegetarians (vegans), who eat none of these foods are in danger of deficiency. Problems for everyone arise with age, however; the stomach may become less able to absorb B 12 and deficiency may result. Pernicious anemia is the classic B 12 deficiency disease and may take years to appear. Other health problems that may be linked to B 12 deficiency include infertility, nervous system disorders, and walking difficulties.

Cooking results in few losses of B 12 , and toxicity is not a danger. The RDA for B 12 for adults is 2 micrograms.

Folacin (folic acid, or folate)

Folacin is essential for cell growth and division.

Women, especially pregnant women, and alcoholics are most likely to be folacin deficient. Signs of deficiency include anemia, weakness, pallor, headaches, forgetfulness, sleeplessness, and irritability. Vitamin B 12 deficiency can aggravate folacin deficiency because B 12 is essential to release folacin from bodily storage. Other health problems that may be associated with folacin deficiency include depression, dementia, neuropsychological disorders, toxemia of pregnancy, infections, and fetal damage.

Folacin is widely distributed in fruits and vegetables, but it is easily destroyed during cooking and storage. The RDA for folacin for adult men is 200 micrograms and for women, 180 micrograms.

Biotin

Biotin is essential for overall growth and well-being. It is important in the metabolism of fats and in the utilization of carbon dioxide.

The best sources of biotin are liver, egg yolks, soy flour, cereals, and yeast. It is also produced by intestinal bacteria, although it is not known whether this form is readily absorbed by the body. Deficiencies are most often produced by the ingestion of large amount of raw egg white, which contains a biotin-binding protein called avidin that prevents the absorption of biotin. Symptoms of deficiency include nausea, vomiting, swelling of the tongue, pallor, depression, hair loss, and dry scaly dermatitis.

 

Recommended Dietary Allowances for Water-Soluble Vitamins

 

Recommended Dietary Allowances for Water-Soluble Vitamins
Age Vit. C Thiamin Riboflav. Niacin Vit. B6 Folate Vit. B12
(mg) (mg) (mg) (mg) (mg) (meg) (meg)
Infants 0 to .5 30 0.3 0.4 5 0.3 25 0.3
.5 to 1 35 0.4 0.5 6 0.6 35 0.5
Children 1 to 3 40 0.7 0.8 9 1 50 0.7
4 to 6 45 0.9 1.1 12 1.1 75 1
7 to 10 1 1.2 13 1.4 100 1.4
Males 11 to 14 50 1.3 1.5 17 1.7 150 2
15 to 18 60 1.5 1.8 20 2 200
19 to 24 1.7 19
25 to 50
51 + 1.2 1.4 15 150
Females 11 to 14 50 1.1 1.3 1.4 180
15 to 18 60 1.5
19 to 24 1.6
25 to 50 1.1
51 + 1 1.2 13
Pregnant 70 1.5 1.6 17 2.2 400 2.2
Nursing 1st 6 months 95 1.6 1.8 20 2.1 280 2.6
2nd 6 months 90 1.7 20 260

The RDA for adults is a wide range: from 30 to 100 micrograms. Toxicity from a normal diet is not a concern.

Pantothenic acid

Pantothenic acid is essential for general growth and well-being. It is an important component in a number of metabolic reactions such as the release of energy from carbohydrates, fats, and proteins and the synthesis of sterols and steroid hormones.

Pantothenic acid is widely distributed among foods, chiefly animal tissues, cereals, and legumes. Evidence of dietary deficiency of pantothenic acid has not been clinically recognized in humans, and there is no specific disease associated with pantothenic acid deficiency.

Pantothenic acid is measured in milligrams. There is no RDA, but daily consumption by adults of between 4 and 7 mg is considered safe. Toxicity from a normal diet is not a concern.

Minerals

Minerals are another component of basic nutritional needs. All living things extract them from the soil, which is their ultimate source. Like vitamins, they are needed for normal metabolism and must be present in the diet in sufficient amounts for the maintenance of good health. The essential minerals are calcium, phosphorus, magnesium, iodine, iron, zinc, selenium, molybdenum, copper, manganese, fluoride, and chromium.

Calcium

Calcium is essential for bone growth, development, and retention as well as for proper nerve conduction, muscle contraction, blood clotting, and membrane permeability.

Dairy products are the primary sources of calcium, but the mineral is also found in green leafy vegetables and soft bones, such as those of sardines and salmon. Maximum calcium ingestion is extremely important during the years from birth to age 25, when the body reaches its peak bone mass. Deficiencies are most common in women and have been linked to the development of osteoporosis in the later years.

The RDA for calcium for children between the ages of 11 and 24 is 1,200 mg. For adults over 24 the RDA is 800 mg. Ingestion of very large amounts of calcium may inhibit the absorption of iron, zinc, and other essential minerals.

Phosphorus

Phosphorus is a structural component of all cells. It is a part of DNA, and is therefore essential in the growth, maintenance, and repair of all body tissues. It is also critical for energy transfer and production.

Phosphorus is present in nearly all foods, principally cereals and proteins. Deficiency is a serious concern only for premature infants fed exclusively human milk.

The RDA for phosphorus is the same as that for calcium. Toxicity from a normal diet is not a concern.

Magnesium

Like phosphorus, magnesium is a structural component in soft tissue cells and is therefore important in the growth, maintenance, and repair of these tissues. It is also important in energy production, lipid and protein synthesis, the formation of urea, muscle relaxation, and in the prevention of tooth decay.

The best sources of magnesium are nuts, legumes, unmilled grains, and green vegetables. Deficiencies from a normal diet are rare and are related instead to various diseases such as those of the gastrointestinal tract, kidney dysfunction, and malnutrition and alcoholism. Symptoms of deficiency include weakness, confusion, personality changes, muscle tremor, nausea, lack of coordination, and gastrointestinal disorders.

The RDA for adult men is 350 mg and for adult women 280 mg.

Iodine

Iodine is an essential component of thyroid hormone, which is important in cellular reactions, metabolism, and growth and development.

Iodized salt and water are the most common sources, and most animal foods contain adequate supplies depending on the soil quality and the amount of iodine added to animal feeds. Iodine is also added in the processing of bread dough. Deficiencies in the United States is not common. The classic deficiency disease in adults is goiter. Iodine deficient fetuses are at a risk of developing cretinism.

The RDA for iodine for adults is 150 micrograms.

Iron

As an essential component of hemoglobin, iron is necessary for the proper transfer of oxygen to cells. It is also important for energy production and collagen synthesis.

Many Americans don’t get enough iron. Women and very young children get the least, followed by the elderly. Iron deficiency leads to anemia: muscles become weak, fatigue, listlessness, and a tendency to tire easily set in. Even mild iron deficiency, however, can affect a person’s intellectual capabilities, especially children’s. Symptoms of deficiency in children include irritability, hyperactivity, learning problems, shortened attention span, poor motivation, and poor intellectual performance.

There are two types of iron, heme and nonheme. Heme comes from animal foods and is much more readily absorbed than nonheme iron, which comes from vegetables. When eaten together, however, the rate of absorption for nonheme iron increases significantly. Also, iron eaten with just a little vitamin C dramatically increases its absorption. Tannins (in tea and red wine) block iron absorption. Iron-rich foods include liver and other organ meats, beef, dried fruits, legumes, dark green leafy vegetables, prune juice, and whole grain cereals.

The RDA for adult males is 10 mg and for adult women 15 mg. There is little danger of toxicity from a normal diet, although some people have an inherited defect in regulating iron absorption and can easily get too much.

Zinc

Zinc is essential for cell multiplication, tissue regeneration, sexual maturity, and proper growth. It is also important as a cofactor in more than 20 enzymatic reactions and serves as a binder in many others.

Severe zinc deficiency is not a problem in the United States, but the effects of mild deficiency—common especially in children, women, and the elderly—on overall health are feared to be widespread. Signs of deficiency include loss of appetite, stunted growth in children, skin changes, small sex glands in boys, delayed sexual maturation, impotence, loss of taste sensitivity, white spots on fingernails, delayed wound-healing, dull hair color.

Animal foods are good sources of zinc as are oysters, milk, egg yolks, and whole grains. Toxicity is rare. The RDA for adults is 12 mg.

Selenium

Selenium functions in a similar way to vitamin E, as an antioxidant helping to protect cells from destruction by toxic agents. Its consumption has also been associated with lower incidences of cancer and heart disease.

Good sources of selenium include whole grains, seafood, liver, kidney, meat, seeds, and nuts. Deficiency may be a problem in areas with selenium-poor soils. Selenium is toxic at higher than trace amounts. The RDA for adult males is 70 micrograms and for adult women 55 micrograms.

Molybdenum

Molybdenum is essential in the function of certain enzyme systems and is also necessary in iron metabolism.

Sources of molybdenum include meats, whole grains, legumes, leafy vegetables, and organ meats. The molybdenum content of vegetables varies widely depending on the content of the soil in which they were grown. Deficiency is not known in humans. Ingesting more than trace amounts is not recommended. The RDA for adults is between 75 and 250 micrograms.

Copper

Copper is important as a cofactor in several enzyme systems and as a catalyst in the synthesis of hemoglobin. It also aids in collagen formation and is involved in the synthesis of phospholipids, which maintain health nerve fibers.

Copper deficiency is believed to be more common than once thought, and it has been linked to heart disease, central nervous system disorders, anemia, and bone disorders. Good sources of copper include shellfish, liver, nuts and seeds, meats, and green leafy vegetables. Copper supplements are not recommended because they can interfere with other minerals, and copper is toxic at more than trace amounts. The RDA for copper is 1.5 to 3 mg.

Manganese

Manganese has a variety of functions, some that other minerals can perform in its place. It is known to play a role in such things as collagen formation, urea formation, synthesis of fatty acids and cholesterol, digestion of proteins, normal bone formation and development, and protein synthesis.

Manganese deficiency has not been observed in humans. Sources of manganese include liver, kidney, spinach, whole grain cereals and breads, dried peas and beans, and nuts. Excessive intake of manganese can interfere with iron absorption. More than trace amounts of manganese are not recommended. The RDA is 2 to 5 mg.

Fluoride

Fluoride is essential for the development of healthy teeth and bones and the prevention of tooth decay.

Fluoride deficiency shows up in increased incidences of tooth decay. Fluoridated water is a most common source of fluoride for many people. For those without access to such water fluoride tablets or toothpaste are helpful. Fish, tea, milk, and eggs are also sources of fluoride. The RDA for adults is between 1.5 and 4 mg.

Chromium

Chromium is important for maintaining normal glucose metabolism. It also acts as a cofactor for insulin.

Chromium deficiency can show up in the form of glucose intolerance in malnourished children and in some diabetics. Sources of chromium include whole grains, brewer’s yeast, meats, and cheeses. Hard water also contains chromium. Chromium intake should not exceed trace amounts. The RDA for adults is between 50 and 200 micrograms.

Fiber

Fiber in the diet is important for proper elimination. It provides bulk, and its use has been linked to the prevention of many health problems: constipation, appendicitis, colon cancer, diverticular disease, spastic colon, hiatal hernia, varicose veins, hemorrhoids, coronary heart disease, high blood pressure, gallstones, diabetes, obesity, ulcerative colitis, and Crohn’s disease.

Fiber is found almost exclusively in plant foods and comes in basically two types: water soluble or water insoluble. Soluble fiber is found primarily in fruits and vegetables and in oat bran in the form of gums and pectin and affects the way the body metabolizes sugars and fats. Insoluble fiber is primarily associated with whole grains, the traditional ‘bran,’ such as wheat bran and rice bran, and is the fiber we think of when we think of laxatives. Generally, the less processed the food, the higher it is in either kind of fiber.

Fiber in high doses can affect the absorption of other vitamins and minerals as well as cause flatulence, bloating, nausea, diarrhea, and impaction or rupture of the bowl. Daily consumption of 35 to 40 grams of fiber is recommended for optimum health and safety.

Water

Water is not really a food in the fuel sense, but it is in many ways a crucial component of nutrition: the body’s need for water is second only to its need for oxygen. It makes up from 55 to 65 percent of the body’s weight, and is constantly being eliminated in the form of urine, perspiration, and expired breath. It must therefore be replaced regularly, for while a person can live for weeks without food, he can live for only a few days without water.

Normally, the best guide to how much water a person needs is his sense of thirst. The regulating mechanism of excretion sees to it that an excessive intake of water will be eliminated as urine. The usual water requirement is on the order of two quarts a day in addition to whatever amount is contained in the solids which make up the daily diet.

Read more: http://www.faqs.org/health-encyc/Nutrition-and-Weight-Control/Nutrition-and-Weight-Control-Basic-nutritional-requirements.html#ixzz33LZWsSRN

Oktober 2, 2017

status palsu: NOBEL KEDOKTERAN FISIOLOGI : jam tubuh (d.h. melatonin obat TIDUR…. kah)

Filed under: Medicine — bumi2009fans @ 5:47 pm

What Is the Circadian Rhythm?

Often referred to as the “body clock”, the circadian rhythm is a cycle that tells our bodies when to sleep, rise, eat–regulating many physiological processes. This internal body clock is affected by environmental cues, like sunlight and temperature. When one’s circadian rhythm is disrupted, sleeping and eating patterns can run amok. A growing body of research is examining the adverse health effects a disrupted circadian rhythm can have, like increasing the chances of cardiovascular events, obesity, and a correlation with neurological problems like depression and bipolar disorder.

time.com: (STOCKHOLM) — Three Americans won the Nobel Prize in Physiology or Medicine on Monday for their discoveries about the body’s daily rhythms, opening up whole new fields of research and raising awareness about the importance of getting enough sleep.
Jeffrey C. Hall, Michael Rosbash and Michael W. Young won the 9-million-kronor ($1.1 million) prize for their work on finding genetic mechanisms behind circadian rhythms — which adapt the workings of the body to different phases of the day, influencing sleep, behavior, hormone levels, body temperature and metabolism.
They “were able to peek inside our biological clock and elucidate its inner workings,” the Nobel citation said.
The work was done using fruit flies as model organisms.
“I am very pleased for the fruit fly,” Rosbash, a 73-year-old professor at Brandeis University, told The Associated Press. He said he got the call about the award just after 5 a.m.
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“When the landline rings at that hour, normally it is because someone died,” he said. “”I’m still a little overwhelmed.”
But he added “I stand on the shoulders of giants. This is a very humbling award.”
Young is at Rockefeller University and Hall has been associated with the University of Maine.
The winners have raised “awareness of the importance of a proper sleep hygiene” said Juleen Zierath of the Nobel Assembly at the Karolinska Institute, which chooses the laureates. Carlos Ibanez, another assembly member, said the research was important in understanding how humans adapt to shiftwork.

Michael Hastings, a scientist at the U.K. Medical Research Council, said the discoveries had opened up a whole new field of study for biology and medicine.
“Until then, the body clock was viewed as a sort of black box,” Hastings told The Associated Press. “We knew nothing about its operation. But what they did was get the genes that made the body clock, and once you’ve got the genes, you can take the field wherever you want to.”
“It’s a field that has exploded massively, propelled by the discoveries by these guys,” he told the AP.
The awardees’ work stems back to 1984, when Rosbash and Hall, who was then also at Brandeis, along with Young isolated the “period gene” in fruit flies. Hall and Rosbash found that a protein encoded by the gene accumulated during the night and degraded during daytime. A decade later, Young discovered another “clock gene.”
“The paradigm-shifting discoveries by the laureates established key mechanisms for the biological clock,” the Nobel Assembly said.
“Our wellbeing is affected when there is a temporary mismatch between our external environment and this internal biological clock, for example when we travel across several time zones and experience ‘jet lag,'” the statement said. “There are also indications that chronic misalignment between our lifestyle and the rhythm dictated by our inner time keeper is associated with increased risk for various diseases.”
That misalignment may be associated with diseases including cancer and degenerative neurological conditions.”Circadian dysfunction has been linked to sleep disorders, as well as depression, bipolar disorder, cognitive function, memory formation and some neurological diseases,” a Nobel background report said.

rose KECIL

Martha Hotz Vitaterna, Ph.D., Joseph S. Takahashi, Ph.D., and Fred W. Turek, Ph.D.

MARTHA HOTZ VITATERNA, PH.D., is a senior research associate in the Center for Functional Genomics, Northwestern University, Evanston, Illinois.

JOSEPH S. TAKAHASHI, PH.D., is the director of the Center for Functional Genomics, the Walter and Mary E. Glass Professor in the Department of Neurobiology and Physiology, and an investigator at the Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois.

FRED W. TUREK, PH.D., is the director of the Center for Sleep and Circadian Biology and is the Charles T. and Emma H. Morrison Professor in the Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois.

The daily light-dark cycle governs rhythmic changes in the behavior and/or physiology of most species. Studies have found that these changes are governed by a biological clock, which in mammals is located in two brain areas called the suprachiasmatic nuclei. The circadian cycles established by this clock occur throughout nature and have a period of approximately 24 hours. In addition, these circadian cycles can be synchronized to external time signals but also can persist in the absence of such signals. Studies have found that the internal clock consists of an array of genes and the protein products they encode, which regulate various physiological processes throughout the body. Disruptions of the biological rhythms can impair the health and well-being of the organism. KEY WORDS: circadian rhythm; time of day; biological regulation; biological adaptation; temperature; light; hypothalamus; neural cell; gene expression; mutagenesis; sleep disorder; physiological AODE (effects of alcohol or other drug use, abuse, and dependence)

One of the most dramatic features of the world in which we live is the cycle of day and night. Correspondingly, almost all species exhibit daily changes in their behavior and/or physiology. These daily rhythms are not simply a response to the 24-hour changes in the physical environment imposed by the earth turning on its axis but, instead, arise from a timekeeping system within the organism. This timekeeping system, or biological “clock,” allows the organism to anticipate and prepare for the changes in the physical environment that are associated with day and night, thereby ensuring that the organism will “do the right thing” at the right time of the day. The biological clock also provides internal temporal organization and ensures that internal changes take place in coordination with one another.

The synchrony of an organism with both its external and internal environments is critical to the organism’s well-being and survival; a lack of synchrony between the organism and the external environment may lead to the individual’s immediate demise. For example, if a nocturnal rodent were to venture from its burrow during broad daylight, the rodent would be exceptionally easy prey for other animals. Similarly, a lack of synchrony within the internal environment might lead to health problems in the individual, such as those associated with jet lag, shift work, and the accompanying sleep loss (e.g., impaired cognitive function, altered hormonal function, and gastrointestinal complaints).

The mechanisms underlying the biological timekeeping systems and the potential consequences of their failure are among the issues addressed by researchers in the field of chronobiology.1  ( 1 For a definition of this and other technical terms used in this article and throughout this issue of the journal, please see glossary, p. 92.)   In its broadest sense, chronobiology encompasses all research areas focusing on biological timing, including high-frequency cycles (e.g., hormone secretion occurring in distinct pulses throughout the day), daily cycles (e.g., activity and rest cycles), and monthly or annual cycles (e.g., reproductive cycles in some species). Among these interrelated areas of chronobiology, this article focuses on one frequency domain-the daily cycles known as circadian rhythms. (The term “circadian” derives from the Latin phrase “circa diem,” which means “about a day.”) Although virtually all life forms- including bacteria, fungi, plants, fruit flies, fish, mice, and humans-exhibit circadian rhythms, this review is primarily limited to the mammalian system. Other animals are discussed only in cases in which they have contributed to the understanding of the mammalian system, particularly in studies of the molecular genetic makeup of the time-keeping system. (For comparative discussions of other nonmammalian model systems that have contributed to the depth of understanding of circadian rhythmicity in mammals, the reader is referred to Wager-Smith and Kay 2000.) Overall, this article has the following major objectives: (1) to provide a highly selective historical overview of the field, (2) to review characteristic properties of circadian rhythms, (3) to define the structural components and the molecular genetic mechanisms comprising the biological clock, and (4) to explore the health effects of biological rhythms.

Historical Overview of Chronobiology

Researchers began studying biological rhythms approximately 50 years ago. Although no single experiment serves as the defining event from which to date the beginning of modern research in chronobiology, studies conducted in the 1950s on circadian rhythmicity in fruit flies by Colin Pittendrigh and in humans by Jurgen Aschoff can be considered its foundation. The area of sleep research, which also is subsumed under the field of chronobiology, evolved some-what independently, with the identification of various sleep stages by Nathaniel Kleitman around the same time (Dement 2000). The legacies of these pioneers continue today with the advancement of the fields they founded.

The roots of the study of biological rhythms, however, reach back even further, to the 1700s and the work of the French scientist de Mairan, who published a monograph describing the daily leaf movements of a plant. De Mairan observed that the daily raising and lowering of the leaves continued even when the plant was placed in an interior room and thus was not exposed to sunlight. This finding suggested that the movements represented something more than a simple response to the sun and were controlled by an internal clock.

Characteristic Properties of Circadian Rhythms

 De Mairan’s apt observations illustrate one critical feature of circadian rhythms- their self-sustained nature. Thus, almost all diurnal rhythms that occur under natural conditions continue to cycle under laboratory conditions devoid of any external time-giving cues from the physical environment (e.g., under constant light or constant darkness). Circadian rhythms that are expressed in the absence of any 24-hour signals from the external environment are called free running. This means that the rhythm is not synchronized by any cyclic change in the physical environment. Strictly speaking, a diurnal rhythm should not be called circadian until it has been shown to persist under constant environmental conditions and thereby can be distinguished from those rhythms that are simply a response to 24-hour environmental changes. For practical purposes, however, there is little reason to distinguish between diurnal and circadian rhythms, because almost all diurnal rhythms are found to be circadian. Nor is a terminology distinction made among circadian rhythms based on the type of environmental stimulus that synchronizes the cycle.

The persistence of rhythms in the absence of a dark-light cycle or other exogenous time signal (i.e., a Zeitgeber) clearly seems to indicate the existence of some kind of internal timekeeping mechanism, or biological clock. However, some investigators have pointed out that the persistence of rhythmicity does not necessarily exclude the possibility that other, uncontrolled cycles generated by the Earth’s revolution on its axis might be driving the rhythm (see Aschoff 1960).

The hypothesis that such uncontrolled geomagnetic cues might play a role in the persistence of rhythmicity can be refuted by a second characteristic feature of circadian rhythms: These cycles persist with a period of close to, but not exactly, 24 hours. If the rhythms were exogenously driven, they should persist with a period of exactly 24 hours. The seeming imprecision is an important feature of rhythmicity, however. As Pittendrigh (1960) demonstrated, the deviation from a 24-hour cycle actually provides a means for the internal time-keeping system to be continuously aligned by and aligned to the light-dark environment. This continuous adjustment results in greater precision in controlling the timing, or phase, of the expressed rhythms, because little drift is allowed to occur before the rhythm is “reset” to the correct phase.

A third characteristic property of circadian rhythms is their ability to be synchronized, or entrained, by external time cues, such as the light-dark cycle. Thus, although circadian rhythms can persist in the absence of external time cues (meaning that they are not driven by the environment), normally such cues are present and the rhythms are aligned to them. Accordingly, if a shift in external cues occurs (e.g., following travel across time zones), the rhythms will be aligned to the new cues. This alignment is called entrainment.

Initially, it was unclear whether entrainment was achieved by modulating the rate of cycling (i.e., whether the cycle was shortened or lengthened until it was aligned to the new cues and then reverted to its original length) or whether entrainment was achieved by discrete “resetting” events. Experiments resulting from this debate led to fundamental discoveries. For example, researchers discovered that the organism’s response to light (i.e., whether a cycle advances, is delayed, or remains unchanged) differs depending on the phase in the cycle at which it is presented (Pittendrigh 1960). Thus, exposure to light during the early part of the individual’s “normal” dark period generally results in a phase delay, whereas exposure to light during the late part of the individual’s normal dark period generally results in a phase advance. This difference in responses can be represented by a phase-response curve (see figure 1 for a schematic illustration of a circadian cycle as well as a phase-response curve). Such a curve can predict the manner in which an organism will entrain not only to shifts in the light-dark cycles but also to unusual light cycles, such as non-24-hour cycles or different light:dark ratios. The existence of a phase-response curve also implies that entrainment is achieved by discrete resetting events rather than changes in the rate of cycling.

In addition to the timing of the light exposure, the light intensity can modulate cycling periods when organisms are left in constant light. Thus, exposure to brighter light intensities can lengthen the period in some species and shorten it in other species. This phenomenon has been dubbed “Aschoff’s rule”(Aschoff 1960). Ultimately, both mechanisms of entrainment appear to be aspects of the same thing, because the consequences of Aschoff’s rule can be predicted or explained by the phase-response curves to light.

Although the light-dark cycle clearly is the major Zeitgeber for all organisms, other factors-such as social interactions, activity or exercise, and even temperature-also can modulate a cycle’s phase. The influence of temperature on circadian rhythms is particularly interesting in that a change in temperature can affect the phase of a cycle without substantially altering the rate of cycling. This means that the cycle may start at an earlier or later-than-normal time but still have the same length. On the one hand, this ability of the internal clock’s pacemaker to compensate for changes in temperature is critical to its ability to predict and adapt to environmental changes, because a clock that speeds up and slows down as the temperature changes would not be useful. On the other hand, temperature compensation also is rather puzzling, because most kinds of biological processes (e.g., biochemical reactions in the body) are accelerated or slowed by temperature changes. Ultimately, this riddle has provided a clue to the nature of the internal clock- that is, the fact that circadian rhythms have a genetic basis. Such a program of gene expression would be more resistant to temperature alteration than, for example, a simple biochemical reaction.

Two final properties of circadian rhythms also provide important hints of the rhythms’ makeup. One of these properties is the rhythms’ ubiquity in nature: Circadian rhythms exist in a broad array of biological processes and organisms, with similar properties and even similar phase-response curves to light. The other property is that circadian rhythms appear to be generated at the cellular level, because the rhythms of unicellular organisms (e.g., algae or the dinoflagellate Gonyaulax) are much the same as rhythms of highly complex mammals. Both of these observations suggest that a cycle in the activation (i.e., expression) of certain genes might underlie the timekeeping mechanism.

  Figure 1 Circadian rhythm responses to light.

A. Parameters of circadian rhythm

A representative circadian rhythm is depicted in which the level of a particular measure (e.g., blood hormone levels and activity levels) varies according to time. The difference in the level between peak and trough values is the amplitude of the rhythm. The timing of a reference point in the cycle (e.g., the peak) relative to a fixed event (e.g., beginning of the night phase) is the phase. The time interval between phase reference points (e.g., two peaks) is called the period. The rhythm shown persists even in continuous darkness (i.e., is free running).

B. Resetting the circadian rhythm

The effects of a rhythm-resetting signal, such as exposure to light by animals other-wise kept in continuous darkness, can shift the rhythm either back (upper panel) or ahead (lower panel), depending on when during the cycle the signal is presented. In the case of a phase delay, the peak levels are reached later than they would be had the rhythm not been shifted. In the case of a phase advance, the peak levels are reached earlier than they would be had the rhythm not been shifted. The black line shows how cycling would appear if the rhythm remained unchanged.

C. Changes in circadian rhythm in response to changes in light exposure

Virtually all species show similar phase-dependent-resetting responses to light, which can be expressed as a phase-response curve. Exposure to light during the early part of the animal’s night causes a phase delay, whereas exposure to light in the latter part of the animal’s night causes a phase advance. Light exposure during the animal’s usual daytime period produces little or no phase shift.

The Anatomical Organization of the Internal Clock

Although studies of unicellular organisms point to the cellular nature of the system generating circadian rhythms, the circadian pacemaker in higher organisms is located in cells of specific structures of the organism. These structures include certain regions of the brain (i.e., the optic and cerebral lobes) in insects; the eyes in certain invertebrates and vertebrates; and the pineal gland, which is located within the brain, in nonmammalian vertebrates. In mammals, the circadian clock resides in two clusters of nerve cells called the suprachiasmatic nuclei (SCN), which are located in a region at the base of the brain called the anterior hypothalamus.

The role of the SCN was demonstrated by the landmark discovery in the early 1970s that by damaging (i.e., lesioning) the SCN in rats, researchers could disrupt and abolish endocrine and behavioral circadian rhythms (for a review, see Klein et al. 1991). Furthermore, by transplanting the SCN from other animals into the animals with the lesioned SCN, investigators could restore some of the circadian rhythms. Finally, the SCN’s role as a master pacemaker regulating other rhythmic systems was confirmed by similar studies in hamsters, which demonstrated that the restored rhythms exhibited the clock properties (i.e., the period, or phase, of the rhythm) of the donor rather than of the host (Ralph et al. 1990). The discovery that the SCN is the site of primary regulation of circadian rhythmicity in mammals gave researchers a focal point for their research: if one wanted to understand 24-hour timekeeping, one needed to study the clock in the SCN.

Recently, however, researchers have been surprised to find that circadian rhythms could persist in isolated lungs, livers, and other tissues grown in a culture dish (i.e., in vitro) that were not under the control of the SCN (Yamazaki et al. 2000). These observations indicate that most cells and tissues of the body may be capable of modulating their activity on a circadian basis. Such findings do not, however, diminish the central role played by the SCN as the master circadian pacemaker that some-how coordinates the entire 24-hour temporal organization of cells, tissues, and the whole organism. The physiological mechanisms underlying this coordination include signals emitted by the SCN that act on other nerve cells (i.e., neural signals) or which are also distributed through the blood to other organs (i.e., neurohormonal signals). To date, however, the characteristics of the circadian signal itself-that is, the specific manner in which the SCN “talks” to the rest of the body-remain unknown (see Stokkan et al. 2001).

Although the effects of SCN lesions on numerous rhythms have been elucidated, their effects on sleep are less clear. Thus, SCN lesions clearly disrupt the consolidation and pattern of sleep in rats but have only minimal effects on the animals’ amount of sleep or sleep need (Mistlberger et al. 1987). For this and other reasons, researchers have postulated that sleep is subject to two essentially independent control mechanisms: (1) the circadian clock that modulates the propensity for sleep and (2) a homeostatic control that reflects the duration of prior waking (i.e., “sleep debt”). Recently, however, studies in squirrel monkeys found that SCN lesions can affect the amount of sleep. Moreover, sleep studies in mice carrying changes (i.e., mutations) in two of the genes influencing circadian cycles (i.e., the DBP and Clock genes) indicated that these mutations resulted in changes in sleep regulation (Naylor et al. 2000; Franken et al. 2000). Both of these observations raise the intriguing possibility that the homeostatic and circadian controls may be more interrelated than researchers previously thought.

Molecular Genetics of Circadian Rhythms

As discussed previously, the properties of circadian clocks suggested cyclic changes in the expression of certain genes as a possible mechanism underlying the internal pacemaker. This hypothesis was supported by the demonstration in a number of species that the expression of genes and the production of proteins encoded by those genes were required for normal clock function. Nevertheless, a completely different experimental approach ultimately led to the identification of molecular circadian clock components. Researchers used chemical agents to introduce numerous, random mutations into the DNAs of the fruit fly, Drosophila melanogaster, and of the filamentous fungus Neurospora. The resulting mutant organisms then were screened for rhythm abnormalities. This mutagenesis approach led to the identification of the first circadian clock mutants, which were called period (per) and frequency (frq, pronounced “freak”). The genes that carried the mutations in these organisms were cloned in the 1980s (for a review, see Wager-Smith and Kay 2000). However, considerable frustration ensued as researchers sought to isolate the equivalent genes in mammals (i.e., mammalian homologs). Finally, in the early 1990s, researchers began a similar mutagenesis screening approach in the mouse and described the first mouse circadian mutation, called Clock, in 1994 (see King and Takahashi 2000). In 1997 the gene affected by this mutation became the first mammalian circadian clock gene to be cloned (King and Takahashi 2000). Like the mutants of the Per and Frq genes, the altered Clock gene both affected the free-running rhythm period (i.e., lengthened the period) and caused a loss of persistence of circadian rhythms under constant environmental conditions. Both the Clock mutant in mice and the Per mutant in flies were the first animals of their respective species identified using such a mutagenesis approach in which the mutation manifested as altered behavior rather than an altered physiological process.

Since the discovery of the Clock gene in mice, the list of circadian clock genes identified in mammals has grown in a remarkably short period of time (see table 1). For example, researchers have identified not one, but three mammalian genes that correspond to the per gene in both their structure (i.e., nucleotide sequence) and their function (King and Takahashi 2000; Lowrey and Takahashi 2000). Some of the pro-posed circadian clock genes have been identified solely based on their similarity in sequence to Drosophila clock genes and have not been confirmed to have clock function based on an examination of the behavior of the corresponding mutants. Nevertheless, the findings to date clearly indicate the outline of a pacemaker that is based on a feedback cycle of gene expression (see figure 2).

Table 1 Mammalian Circadian Clock Genes; the Corresponding Genes in the Fruit Fly, Drosophila; and the Effects of Changes (i.e., Mutations) in Those Genes on the Behavior (i.e., Phenotype) of the Affected Animals

Mouse Gene Alias Drosophila Gene Mutant Phenotype
 *Clock    dClock Lengthened period; loss of persistent rhythmicity in constant conditions
 mPer1   period Reduced amplitude, shortened period, or loss of rhythm
*mPer2    period Shortened period, loss of rhythm
*mPer3   period Modest shortening of period
*CKÉє tau (hamster) doubletime Shortened period in hamster mutants
*mCry1 mCry2   dcry Animals lacking the mCry1 gene (i.e., mCry1 knockouts) have shortened period; mCry2 knockouts have lengthened period; animals lacking both genes (i.e., double knockouts) have a loss of rhythm
*BMAL1 MOP3 cycle  Loss of rhythm
?mTim   timeless Role in mammals is not clear
?DBP     Modest lengthening of period

 

NOTE: Asterisk (*) indicates that a key role for the gene in timekeeping has been demonstrated by the phenotype of a mutant.

Figure 2 Schematic representation of the regulation of genes believed to be involved in the circadian clock. BMAL1, Clock, CK1є, mPer, and mCry all are circadian clock genes identified in mice. (Several variants exist of the mPer and mCry genes.) In the cell’s nucleus, the genetic information encoded in these genes is converted into a carrier molecule called mRNA (black wavy lines), which is transported into the fluid within the cell (i.e., the cytoplasm). There, the mRNA is used to generate the protein products encoded by the circadian clock genes (circles and ovals with colors corresponding to the respective genes). Some of these proteins regulate the activity of certain clock genes by binding to “molecular switches” (i.e., E boxes) located in front of those genes. This is called a feedback cycle. Thus, the BMAL1 and clock proteins promote activation of the Per and mCry genes, whereas Per proteins inhibit activation of those genes. The 24-hour cycling comes about as the BMAL1 and Clock proteins induce increased production of Per and Cry proteins. As Pers and Crys accumulate, they inhibit their own synthesis, and the protein levels decline. CK1є protein also helps to regulate Clock protein levels by destabilizing Per protein.

NOTE: BMAL1 = brain and muscle ARNT-like 1; CK1є = caseine kinase 1 epsilon; mPer = mouse period; mCry = mouse cryptochrome.

Importance of the Circadian Clock for Human Health and Well-Being

Nearly all physiological and behavioral functions in humans occur on a rhythmic basis, which in turn leads to dramatic diurnal rhythms in human performance capabilities. Regardless of whether it results from voluntary (e.g., shift work or rapid travel across time zones) or involuntary (e.g., illness or advanced age) circumstances, a disturbed circadian rhythmicity in humans has been associated with a variety of mental and physical disorders and may negatively impact safety, performance, and productivity. Many adverse effects of disrupted circadian rhythmicity may, in fact, be linked to disturbances in the sleep-wake cycle. Some rhythmic processes are more affected by the circadian clock than by the sleep-wake state, whereas other rhythms are more dependent on the sleep-wake state.

For most animals, the timing of sleep and wakefulness under natural conditions is in synchrony with the circadian control of the sleep cycle and all other circadian-controlled rhythms. Humans, however, have the unique ability to cognitively override their internal biological clock and its rhythmic outputs. When the sleep-wake cycle is out of phase with the rhythms that are con-trolled by the circadian clock (e.g., during shift work or rapid travel across time zones), adverse effects may ensue.

In addition to the sleep disturbances associated with jet lag or shift work, sleep disorders can occur for many other known and unknown reasons. And although disturbed sleep is a hallmark of many human mental and physiological disorders, notably affective disorders, it is often unclear whether the sleep disturbances contribute to or result from the illness. Other circadian rhythm abnormalities also are often associated with various disease states, although again the importance of these rhythm abnormalities in the development (i.e., etiology) of the disease remains unknown (Brunello et al. 2000).

One important factor contributing to researchers’ inability to precisely define the role of circadian abnormalities in various disease states may be the lack of knowledge of how circadian signals from the SCN are relayed to target tissues. To further elucidate the regulation of circadian rhythms, researchers need a better understanding of the nature of circadian signal output from the SCN and of how these output signals may be modified once they reach their target systems. Such an enhanced understanding also would allow for a better delineation of the importance of normal temporal organization for human health and disease. The finding that two major causes of death-heart attacks and strokes- show time-of-day variation in their occurrence is a case in point. If scientists knew more about the mechanisms responsible for the rhythmicity of these disorders, they might be able to identify more rational therapeutic strategies to influence these events. Finally, given that dramatic changes occur in the circadian clock system with advanced age, these changes may underlie, or at least exacerbate, the age-related deterioration in the physical and mental capabilities of older adults.

Conclusions

Although researchers in just the past few years have made great advances in understanding the molecular basis of circadian rhythmicity, this progress builds on extensive research carried out in many laboratories during the past 50 years. Within the same period, other researchers in numerous laboratories have elucidated the critical role played by the SCN in the regulation of circadian rhythmicity in mammals and per-haps other vertebrates. (For more information on these findings and their relevance, the reader can refer to a variety of resources on the World Wide Web, some of which are listed in table 2.)

Most animals are content to obey their SCN and let it orchestrate the expression of a multitude of circadian rhythms. Humans, however, have a mind of their own and often use this mind to disobey their “internal clock”-for example, with an increasing tendency toward 24-hour availability for business. The potential consequences of such an increasingly 24-hour on-call lifestyle are unknown at this point, but the evidence does not bode well.

The challenge for researchers and clinicians now is to determine not only the cause but also the consequences for human health and disease of disruptions in the temporal organization of the circadian system. These issues also include the question of what role alcohol may play in the disruption of normal circadian rhythms and the biological clock.  This question is addressed in more detail in this special issue of Alcohol Research & Health. Drs. Wasielewski and Holloway review ways in which alcohol and the body’s circadian rhythm interact, using body temperature as an index of circadian rhythm function. The sleep-wake cycle, which constitutes a central aspect of circadian rhythms in particular, is subject to modification by alcohol; alcohol’s effects on the sleep of nonalcoholics and alcoholics are discussed by Drs. Roehrs and Roth and by Dr. Brower, respectively.

As indicated in this article, disturbances of the normal circadian rhythmicity can result in serious health consequences, including psychiatric disorders, such as depression. At the same time, psychoactive drugs, such as antidepressants, also have chronobiological effects. Dr. Rosenwasser explores those associations and discusses alcohol’s effects in human and animal models of depression. Other influences of alcohol on the biological clock may be even more subtle and remain rather speculative, such as the consequences of prenatal alcohol expo-sure, which is discussed by Drs. Earnest, Chen, and West. Finally, not only may alcohol consumption affect circadian rhythms, but circadian factors, such as the light-dark cycle, may also influence alcohol consumption. This topic is discussed by Drs. Hiller-Sturmhofel and Kulkosky. Together, these articles offer readers insight into the interesting and complex interactions that exist between alcohol and the circadian rhythms that govern much of the behavior and well-being of all organisms, including humans.

Table 2 Chronobiological Resources on the World Wide Web

Web Site
Description
 http://www.nwu.edu/ccbm/ Web site of Northwestern University’s Center for Sleep and Circadian Biology
http://www.sleepquest.com/ Information site of William Dement’s Sleep Research Center
http://www.med.stanford.edu/school/ Narcolepsy site created by Emmanuel Psychiatry/narcolepsy Mignot at Stanford University
http://www.sleepfoundation.org/ Web site of the National Sleep Foundation
http://www.srbr.org/ Web site of the Society for Research on Biological Rhythms
http://www.cbt.virginia.edu/ Web site of the Center for Biological Timing at the University of Virginia
http://www.hhmi.org/grants/lectures Web site providing Howard Hughes Medical Institute Holiday Lectures

References

ASCHOFF, J. Exogenous and endogenous components in circadian rhythms. Cold Spring Harbor Symposia on Quantitative Biology: Volume XXV. Biological Clocks. New York: Cold Spring Harbor Press, 1960. pp. 11-28.

BRUNELLO, N.; ARMITAGE, R.; FEINBERG, I.; ET AL. Depression and sleep disorders: Clinical relevance, economic burden and pharmacological treatment. Neuropsychobiology 42:107-119, 2000.

DEMENT, W.C. History of sleep physiology and medicine. In: Kryer, M.H.; Roth, T.; and Dement, W.C., eds. Principles and Practice of Sleep Medicine. 3d ed. Philadelphia: W.B. Saunders, 2000

FRANKEN, P.; LOPEZ-MOLINA, L.; MARCACCI, L.; SCHIBLER, U.; AND TAFTI, M. The transcription factor DBP affects circadian sleep consolidation and rhythmic EEG activity. Journal of Neuroscience 20(2):617-625, 2000.

KING, D.P., AND TAKAHASHI, J.S. Molecular genetics of circadian rhythms in mammals. Annual Review of Neuroscience 23:713-742, 2000.

KLEIN, D.C.; MOORE, R.Y.; AND REPPERT, S.M. Suprachiasmatic Nucleus: The Mind’s Clock. New York: Oxford University Press, 1991.

LOWREY, P.L., AND TAKAHASHI, J.S. Genetics of the mammalian circadian system: Photic entrainment, circadian pacemaker mechanisms, and post-translational control. Annual Review of Genetics 34:533-562, 2000.

MISTLBERGER, R.E.; BERGMANN, B.M.; AND RECHTSCHAFFEN, A. Relationships among wake episode lengths, contiguous sleep episode lengths, and electroencephalographic delta waves in rats with suprachiasmatic nuclei lesions. Sleep 10(1): 12-24, 1987.

NAYLOR, E.; BERGMANN, B.M.; KRAUSKI, K.; ET AL. The circadian clock mutation alters sleep homeostasis in the mouse. Journal of Neuroscience 20(21):8138- 8143, 2000.

PITTENDRIGH, C.S. Circadian rhythms and the circadian organization of living systems. Cold Spring Harbor Symposia on Quantitative Biology: Volume XXV. Biological Clocks. New York: Cold Spring Harbor Press, 1960. pp. 159-184.

RALPH, M.R.; FOSTER, R.G.; DAVIS, F.C.; AND MENAKER, M. Transplanted suprachiasmatic nucleus determines circadian period. Science 247:975-978. 1990.

STOKKAN, K.A.; YAMAZAKI, S.; TEI, H.; SAKAKI, Y.; AND MENAKER, M. Entrainment of the circadian clock in the liver by feeding. Science 291:490-493, 2001.

WAGER-SMITH, K., AND KAY, S.A. Circadian rhythm genetics: From flies to mice to humans. Nature Genetics 26:23-27, 2000.

YAMAZAKI, S.; NUMANO, R.; ABE, M.; ET AL. Resetting central and peripheral circadian oscillators in trans-genic rats. Science 288:682-685, 2000.

 

GLOSSARY

Every scientific field has its specific terminology; the scientific area of biological rhythms and sleep is no exception. This glossary defines some of the terms that readers may encounter in this article and throughout this special issue of Alcohol Research & Health.

Chronobiology: A subdiscipline of biology concerned with the timing of biological events, especially repetitive or cyclical phenomena, in individual organisms.

Circadian: A term derived from the Latin phrase “circa diem,” meaning “about a day”; refers to biological variations or rhythms with a cycle of approximately 24 hours. Circadian rhythms are self-sustaining (i.e., free running), meaning that they will persist when the organism is placed in an environment devoid of time cues, such as constant light or constant darkness. For comparison, see diurnal, infradian, and ultradian.

Circadian time (CT): A standardized 24-hour notation of the phase in a circadian cycle that represents an estimation of the organism’s subjective time. CT 0 indicates the beginning of a subjective day, and CT 12 is the beginning of a subjective night. For example, for a nocturnal rodent, the beginning of a subjective night (i.e., CT 12) begins with the onset of activity, whereas for a diurnal species, CT 0 would be the beginning of activity. For comparison, see Zeitgeber time.

DD: A conventional notation for an environment kept in continuous darkness (as opposed to a light-dark cycle). For comparison, see LD.

Diurnal: Varying with time of day. Diurnal rhythms may persist when the organism is placed in an environment devoid of time cues, such as constant light or constant darkness. Therefore, diurnal variations can be either light driven or clock driven. For comparison, see circadian.

Entrainment: The process of synchronization of a timekeeping mechanism to the environment, such as to a light-dark cycle, or LD. For comparison, see free running.

Free running: The state of an organism (or rhythm) in the absence of any entraining stimuli. Typically, subjects are kept in constant dim light or constant darkness to assess their free-running rhythms. For comparison, see entrainment.

Infradian: A term derived from the Latin phrase “infra diem,” meaning “less than a day”; refers to biological cycles that last more than 1 day and, therefore, have a frequency of less than one per day. For comparison, see circadian and ultradian.

LD: Conventional notation for a light-dark environmental cycle; the numbers of hours of light and dark are typically presented separated by a colon. For example, LD 16:8 denotes a cycle consisting of 16 hours of light and 8 hours of dark. For comparison, see DD.

Masking: The obscuring of the “true” state of a rhythm by conditions that prevent its usual expression. Usually, the phase of an entrained rhythm or the absence of entrainment (e.g., in an animal that is unable to entrain because of some defect) is said to be masked by a light cycle. For example, the aversion of a nocturnal rodent to bright light results in its activity onset appearing to coincide with the absence of light, or “lights off,” when the animal actually has been awake for hours. For comparison, see entrainment.

Nonrapid eye movement (NREM) sleep: Sleep stages that include the “deeper” stages of sleep in which dreaming typically does not occur. Also referred to as slow-wave sleep. For comparison, see rapid eye movement sleep.

Phase shift: A change in the phase of a rhythm. This change can be measured by observing a change in the timing of a phase reference point (e.g., activity onset or the nocturnal rise in the release of the hormone melatonin) from the timing expected based on previous, free-running cycles. Phase shifts may be either advances (i.e., the phase reference point occurs earlier than normal) or delays (i.e., the phase reference point occurs later than normal).


Phase-response curve (PRC): 
A graphical summary of the phase shifts produced by a particular manipulation, such as a light pulse or a pharmacological treatment, as a function of the phase (i.e., circadian time) at which the manipulation occurs. Defining the PRC to light has enabled researchers to understand and predict how entrainment to light cycles is accomplished.


Rapid eye movement (REM) sleep: 
A stage of light sleep characterized by rapid eye movements and associated with dreaming. Also called paradoxical sleep. For comparison, see nonrapid eye movement sleep.


Suprachiasmatic nucleus or nuclei (SCN): 
A cluster of nerve cells located in the brain region called the hypothalamus that is responsible for generating and coordinating circadian rhythmicity in mammals.


Ultradian: 
A term derived from the Latin phrase “ultra diem,” meaning “more than a day”; refers to biological cycles that last less than 1 day and, therefore, have a frequency of more than one per day. For comparison, see circadian and infradian.


Zeitgeber: 
A German word literally meaning “time-giver.” A time cue capable of entraining circadian rhythms. Light represents the most important Zeitgeber.


Zeitgeber time (ZT): 
A standardized 24-hour notation of the phase in an entrained circadian cycle in which ZT 0 indicates the beginning of day, or the light phase, and ZT 12 is the beginning of night, or the dark phase. For comparison, see circadian time. 

big-dancing-banana-smiley-emoticon

Sulit Tidur, Coba Makan Anggur!

IGNATIUS SAWABI
………………..ralat gw: melantonin seharusnya ditulis MELATONIN
RABU, 1 JULI 2009 | 18:23 WIB
JAKARTA, KOMPAS.com – Satu lagi manfaat buah anggur. Penderita insomnia atau susah tidur, ternyata bisa terbantu agar mudah memejamkan mata dengan buah ini. Demikian diungkap Ahli Kesehatan Gizi Masyarakat Institut Pertanian Bogor (IPB) Prof. Dr. Ir. Ali Khomsan dalam jumpa pers di Jakarta, Rabu (1/7).

“Rahasianya pada melantonin,” kata Ali. Di dalam buah anggur, lanjut Ali, terdapat hormon yang dinamakan melantonin, hormon yang berfungsi untuk mengatur jam biologis tubuh kita. Mulai jam 18.00 hormon ini mulai membanjiri tubuh kita sampai penuh pada sekitar jam 22.00. “Pada saat itu kita mulai mengantuk dan tidur,” ungkap Ali.

Orang insomnia memiliki sedikit hormon melantonin ini. Tanda-tanda insomnia tidak hanya susah untuk tidur, tapi juga terbangun dari tidur lalu tidak bisa tidur lagi. Salah satu solusinya supaya bisa tidur adalah dengan mengkonsumsi anggur. “1 porsi anggur kiranya cukup,” tutur Ali. 1 porsi anggur sama dengan mengkonsumsi 6-8 buah anggur.

Melantonin ini hanya bekerja di malam hari, sedangkan pada siang hari tidak berfungsi karena ada sinar matahari. “Namun ia sering tertipu. Di saat kita berada di ruang gelap (walaupun pada siang hari) atau temaram maka melantonin akan keluar dan membuat kita mengantuk,” katanya.

Menurut Ali, mengatasi insomnia dengan mengkonsumsi anggur akan lebih baik jika dibarengi dengan minum susu. “Namun belum diketahui kapan lelapnya sejak ia makan anggur,” papar Ali.

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Melatonin Side Effects

Melatonin Facts and Melatonin Dosage

Melatonin side effects can be quite serious, so it’s important to find out about this hormonal supplement before you decide to take it to help with your health conditions.

Melatonin Facts

Melatonin is a naturally occurring bodily hormone produced by your pineal gland that is responsible for your body’s patterns and rhythms.

As such one of the major functions of melatonin supplements is to readjust the body’s biological clock; thereby treating insomnia, jet lag and other sleep disorders.

Some believe that melatonin benefits the immune system as well as prevents cancer and other diseases.

Others speak of the anti-aging benefits of melatonin, citing clinical data showing that melatonin slows down the aging process.

Melatonin Side Effects

As with all hormonal supplements, there are many different potential melatonin side effects to contend with which may make this a unwise choice for your condition, unless you find a quality supplement with recommended dosages.

Hopefully there will be more adequate clinical trials to prove the saftety of melatonin supplements.

Reported melatonin side effects include headaches, nausea, depression, nightmares and vivid dreams, irritability, abdominal cramps and dizziness.

Melatonin facts also point to negative effects on the reproductive system as well as decreased sex drive in both men and women.

Since melatonin is a hormone, it can affect many internal body processes. Melatonin facts show that those with depression might experience worsening symptoms. Others at a higher risk of developing melatonin side effects are people with liver disease, seizure disorders and high blood pressure.
Melatonin Hormone Found in Red Wine Grapes
[Outline] [RSS & Subscription]

According to the research conducted by the scientist Iriti Marcello at the University of Milan it was found that grapes used in the making //of red wine have high levels of melatonin. The study results were published in the journal of science of food and Agriculture. This is a hormone which is secreted by the pineal gland in the brain in all mammals. But now the hormone’s existence in plants has shocked the researcher. It is otherwise called the sleep hormone. It is produced by the body in the night and it regulated the circadian rhythm meaning it tells the body when it is time to sleep. Hence the researches in Italy explain the reason as to why people fall asleep after drinking wine.

The hormone plays a vital role in the sleep-wake patterns and also has antioxidant properties. Some of the grape varieties which have high content of melatonin are Nebbolo, Merlot, Cabernet Savignon, Sangiovesse and Croatina. According to the researchers it was found that the melatonin content could be enhanced in grapes by treating them with a plant vaccine Benzothiadiazole. But Richard Wurtman of the brain and cognitive science department at MIT feels that further in depth investigation has to be done to prove that the substance found in the grapes is melatonin and not any other substance which is similar to the hormone.


Melatonin May Ease Sleep Problems in Autistic Children
Date:4/17/2009

Small study finds over-the-counter melatonin reduces time to slumber

FRIDAY, April 17 (HealthDay News) — Over-the-countermelatonin supplements may help treat sleep problems in children with autism, a small U.S. study shows.

The study included 12 children, aged 2 to 15 years, with autism spectrum disorder, fragile X syndrome (FXS), or both. The participants were randomly selected to take melatonin or a placebo for two weeks. After they completed the first two weeks of the study, the children were switched over to the alternate treatment for another two weeks.

Taking the melatonin increased sleep duration by 21 minutes, shortened sleep-onset latency by 28 minutes, and reduced sleep-onset time by 42 minutes, compared to the placebo. The findings were published in the April 15 issue of the Journal of Clinical Sleep Medicine.

Over-the-counter melatonin supplements benefit children of all ages and help alleviate some of the additional stress experienced by parents of special-needs children, said senior author Beth L. Goodlin-Jones, of the M.I.N.D. Institute at the University of California Davis Health System in Sacramento.

“Sleep-onset problems at the beginning of the night are very troublesome for children and their families. Sometimes children may take one to two hours to fall asleep, and often they disrupt the household during this time,” she said in an American Academy of Sleep Medicine news release.

Goodlin-Jones and colleagues noted that sleep problems occur in up to 89 percent of children with autism and 77 percent of children with FXS, an inherited form of mental impairment that’s the most commonly known cause of autism.

Over-the-counter melatonin supplements, behavior therapies and sleep hygiene practices should be used to manage sleep problems in children with autism and FXS, the researchers recommended.

More information

The U.S. National Library of Medicine has more aboutmelatonin.

— Robert Preidt

SOURCE: American Academy of Sleep Medicine, news release, April 15, 2009

Agustus 24, 2017

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Pandangan SEDERHANA gw @ Brexhit, ooops, BRESHIT, ooops: BREX1T

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the easy way to edit dna

time.com : With the usual mix of anticipation and apprehension, Kaitlyn Johnson is getting ready to go to her first summer camp. She’s looking forward to meeting new friends and being able to ride horses, swim and host tea parties. She’s also a little nervous and a little scared, like any 7-year-old facing her first sleepaway camp.

But the wonder is that Kaitlyn is leaving the house for anything but a medical facility. Diagnosed with leukemia when she was 18 months old, her life has been consumed with cancer treatments, doctors’ visits and hospital stays.

Acute lymphoblastic leukemia is the most common cancer among young children, accounting for a quarter of all cancer cases in kids, and it has no cure. For about 85% to 90% of children, the leukemia can, however, be effectively treated through chemotherapy.

If it is not eliminated and comes back, it is, more often than not, fatal. Rounds of chemotherapy can buy patients time, but as the disease progresses, the periods of remission get shorter and shorter. “The options for these patients are not very good at all,” says Dr. Theodore Laetsch, a pediatrician at the University of Texas Southwestern Medical Center.

When Kaitlyn’s cancer wasn’t controlled after three years and round after round of chemotherapy drugs, her doctors had little else to offer. “They said, ‘This did nothing, it didn’t touch it,'” says Kaitlyn’s mother Mandy, a dental assistant from Royce City, Texas. “My stomach just dropped.” Kaitlyn could receive a bone-marrow transplant, but only about half of those procedures are successful, and there was a good chance that she would reject the donor cells. If that happened, her chances of surviving were very small.

In a calculated gamble, her doctors suggested a radical new option: becoming a test subject in a trial of an experimental therapy that would, for the first time, use gene therapy to train a patient’s immune system to recognize and destroy their cancer in the same way it dispatches bacteria and viruses. The strategy is the latest development in immunotherapy, a revolutionary approach to cancer treatment that uses a series of precision strikes to disintegrate cancer from within the body itself. Joining the trial was risky, since other attempts to activate the immune system hadn’t really worked in the past. Mandy, her husband James and Kaitlyn traveled from their home in Texas to Children’s Hospital of Philadelphia (CHOP), where they stayed in a hotel for eight weeks while Kaitlyn received the therapy and recovered. “The thought crossed my mind that Kaitlyn might not come home again,” says Mandy. “I couldn’t tell you how many times I would be in the bathroom at the hospital, spending an hour in the shower just crying, thinking, What are we going to do if this doesn’t help her?”

But it did. After receiving the therapy in 2015, the cancer cells in Kaitlyn’s body melted away. Test after test, including one that picks up one cancer cell in a million, still can’t detect any malignant cells lurking in Kaitlyn’s blood. What saved Kaitlyn was an infusion of her own immune cells that were genetically modified to destroy her leukemia. “You take someone who essentially has no possibility for a cure–almost every single one of these patients dies–and with [this] therapy, 90% go into remission,” says Dr. David Porter, director of blood and bone-marrow transplantation at the University of Pennsylvania. Such radical immune-based approaches were launched in 2011 with the success of intravenous drugs that loosen the brakes on the immune system so it can see cancer cells and destroy them with the same vigor with which they attack bacteria and viruses. Now, with the genetically engineered immune cells known as chimeric antigen receptor (CAR) T cells that were used in Kaitlyn’s study, doctors are crippling cancer in more precise and targeted ways than surgery, chemotherapy and radiation ever could. While the first cancer immunotherapies were broadly aimed at any cancer, experts are now repurposing the immune system into a personalized precision treatment that can not only recognize but also eliminate the cancer cells unique to each individual patient.

What makes immune-based therapies like CAR T cell therapy so promising–and so powerful–is that they are a living drug churned out by the patients themselves. The treatment isn’t a pill or a liquid that has to be taken regularly, but a one-hit wonder that, when given a single time, trains the body to keep on treating, ideally for a lifetime.

“This therapy is utterly transformative for this kind of leukemia and also lymphoma,” says Stephan Grupp, director of the cancer immunotherapy program at CHOP and one of the lead doctors treating patients in the study in which Kaitlyn participated.

Eager to bring this groundbreaking option to more patients, including those with other types of cancers, an advisory panel for the Food and Drug Administration voted unanimously in July to move the therapy beyond the testing phase, during which several hundred people have been able to take advantage of it, to become a standard therapy for children with certain leukemias if all other treatments have failed. While the FDA isn’t obligated to follow the panel’s advice, it often does, and it is expected to announce its decision in a matter of weeks.

Across the country, doctors are racing to enroll people with other cancers–breast, prostate, pancreatic, ovarian, sarcoma and brain, including the kind diagnosed in Senator John McCain–in hundreds of trials to see if they, too, will benefit from this novel approach. They are even cautiously allowing themselves to entertain the idea that this living drug may even lead to a cure for some of these patients. Curing cancers, rather than treating them, would result in a significant drop in the more than $120 billion currently spent each year on cancer care in the U.S., as well as untold suffering.

Cancer-newest-miracle-cure-06Lon Tweeten for TIME 

This revolutionary therapy, however, almost didn’t happen. While the idea of using the body’s immune cells against cancer has been around for a long time, the practical reality had proved daunting. Unlike infection-causing bacteria and viruses that are distinctly foreign to the body, cancer cells start out as healthy cells that mutate and grow out of control, and the immune system is loath to target its own cells.

“Only a handful of people were doing the research,” says Dr. Carl June, director of the Center for Cellular Immunotherapy at the University of Pennsylvania’s Abramson Cancer Center and the scientist who pioneered the therapy. A graduate of the U.S. Naval Academy, June is all too familiar with the devastating effects of cancer, having lost his first wife to ovarian cancer and battled skin cancer himself. Trial after trial failed as reinfusions of immune cells turned out to be more of a hit-or-miss endeavor than a reliable road to remission.

After spending nearly three decades on the problem, June zeroed in on a malignant fingerprint that could be exploited to stack the deck of a cancer patient’s immune system with the right destructive cells to destroy the cancer.

In the case of leukemias, that marker turned out to be CD19, a protein that all cancerous blood cells sprout on their surface. June repurposed immune cells to carry a protein that would stick to CD19, along with another marker that would activate the immune cells to start attacking the cancer more aggressively once they found their malignant marks. Using a design initially developed by researchers at St. Jude Children’s Research Hospital for such a combination, June and his colleague Bruce Levine perfected a way to genetically modify and grow these cancer-fighting cells in abundance in the lab and to test them in animals with leukemia. The resulting immune platoon of CAR T cells is uniquely equipped to ferret out and destroy cancer cells. But getting them into patients is a complex process. Doctors first remove a patient’s immune cells from the blood, genetically tweak them in the lab to carry June’s cancer-targeting combination and then infuse the modified cells back into the patient using an IV.

Because these repurposed immune cells continue to survive and divide, the therapy continues to work for months, years and, doctors hope, perhaps a lifetime. Similar to the way vaccines prompt the body to produce immune cells that can provide lifelong protection against viruses and bacteria, CAR T cell therapy could be a way to immunize against cancer. “The word vaccination would not be inappropriate,” says Dr. Otis Brawley, chief medical officer of the American Cancer Society.

June’s therapy worked surprisingly well in mice, shrinking tumors and, in some cases, eliminating them altogether. He applied for a grant at the National Cancer Institute at the National Institutes of Health to study the therapy in people from 2010 to 2011. But the idea was still so new that many scientists believed that testing it in people was too risky. In 1999, a teenager died days after receiving an experimental dose of genes to correct an inherited disorder, and anything involving gene therapy was viewed suspiciously. While such deaths aren’t entirely unusual in experimental studies, there were ethical questions about whether the teenager and his family were adequately informed of the risks and concerns that the doctor in charge of the study had a financial conflict of interest in seeing the therapy develop. Officials in charge of the program acknowledged that important questions were raised by the trial and said they took the questions and concerns very seriously. But the entire gene-therapy program was shut down. All of that occurred at the University of Pennsylvania–where June was. His grant application was rejected.

It would take two more years before private funders–the Leukemia and Lymphoma Society and an alumnus of the university who was eager to support new cancer treatments–donated $5 million to give June the chance to bring his therapy to the first human patients.

The date July 31 has always been a milestone for Bill Ludwig, a retired corrections officer in New Jersey. It’s the day that he joined the Marines as an 18-year-old, and the day, 30 years later, that he married his wife Darla.

It was also the day he went to the hospital to become the first person ever to receive the combination gene and CAR T cell therapy, in 2010. For Ludwig, the experimental therapy was his only remaining option. Like many people with leukemia, Ludwig had been living on borrowed time for a decade, counting the days between the chemotherapy treatments that would hold the cancer in his blood cells at bay for a time. Inevitably, like weeds in an untended garden, the leukemia cells would grow and take over his blood system again.

But the periods of reprieve were getting dangerously short. “I was running out of treatments,” says Ludwig. So when his doctor mentioned the trial conducted by June and Porter at the University of Pennsylvania, he didn’t hesitate. “I never thought that the clinical trial was going to cure me,” he says. “I just wanted to live and to continue to fight. If there was something that would put me into the next month, still breathing, then that’s what I was looking for.”

When Ludwig signed the consent form for the treatment, he wasn’t even told what to expect in terms of side effects or adverse reactions. The scientists had no way of predicting what would happen. “They explained that I was the first and that they obviously had no case law, so to speak,” he says. So when he was hit with a severe fever, had difficulty breathing, showed signs of kidney failure and was admitted to the intensive care unit, he assumed that the treatment wasn’t working.

His condition deteriorated so quickly and so intensely that doctors told him to call his family to his bedside, just four days after he received the modified cells. “I told my family I loved them and that I knew why they were there,” he says. “I had already gone and had a cemetery plot, and already paid for my funeral.”

Rather than signaling the end, Ludwig’s severe illness turned out to be evidence that the immune cells he received were furiously at work, eliminating and sweeping away the huge burden of cancer cells choking up his bloodstream. But his doctors did not realize it at the time.

It wasn’t until the second patient, Doug Olson, who received his CAR T cells about six weeks after Ludwig, that Porter had a eureka moment. When he received the call that Olson was also running a high fever, having trouble breathing and showing abnormal lab results, Porter realized that these were signs that the treatment was working. “It happens when you kill huge amounts of cancer cells all at the same time,” Porter says. What threw him off initially is that it’s rare for anything to wipe out that much cancer in people with Ludwig’s and Olson’s disease. June and Porter have since calculated that the T cells obliterated anywhere from 2.5 lb. to 7 lb. of cancer in Ludwig’s and Olson’s bodies. “I couldn’t fathom that this is why they both were so sick,” says Porter. “But I realized this is the cells: they were working, and working rapidly. It was not something we see with chemotherapy or anything else we have to treat this cancer.”

Ludwig has now been in remission for seven years, and his success led to the larger study of CAR T cell therapy in children like Kaitlyn, who no longer respond to existing treatments for their cancer. The only side effect Ludwig has is a weakened immune system; because the treatment wipes out a category of his immune cells–the ones that turned cancerous–he returns to the University of Pennsylvania every seven weeks for an infusion of immunoglobulins to protect him from pneumonia and colds. Olson, too, is still cancer-free.

While the number of people who have received CAR T cell therapy is still small, the majority are in remission. That’s especially encouraging for children, whose lives are permanently disrupted by the repeated cycles of treatments that currently are their only option. “It’s a chance for these kids to have a normal life and a normal childhood that doesn’t involve constant infusions, transfusions, infections and being away from their home, family and school,” says Dr. Gwen Nichols, chief medical officer of the Leukemia and Lymphoma Society.

The hope is that while CAR T cell therapy will at first be reserved for people who have failed to respond to all standard treatments, eventually they won’t have to wait that long. As doctors learn from pioneers like Kaitlyn, Ludwig and Olson, they will have more confidence in pushing the therapy earlier, when patients are stronger and the cancer is less advanced–perhaps as a replacement for or in combination with other treatments.

The severe immune reaction triggered by the therapy remains a big concern. While it can be monitored in the hospital and managed with steroids or antibodies that fight inflammation, there have been deaths in other trials involving CAR T cells. One drug company put one of its studies on hold due to the toxic side effects. “I am excited by CAR T therapy, but I’m also worried that some people might get too excited,” says the American Cancer Society’s Brawley. “It’s important that we proceed slowly and do this meticulously so that we develop this in the right way.”

For now, CAR T cells are expensive–some analysts estimate that each patient’s batch of cells would cost hundreds of thousands of dollars–because they require a bespoke production process. If approved, Novartis, which licensed the technology from the University of Pennsylvania, will provide the therapy in about 35 cancer centers in the U.S. by the end of the year. Other companies are already working toward universal T cells that could be created for off-the-shelf use in any patient with cancer. “This is just the beginning,” says June.

Since Ludwig’s cancer has been in remission, he and his wife have packed their RV and taken the vacations they missed while he was a slave to his cancer and chemotherapy schedule. This year, they’re visiting Mount Rushmore, Grand Teton National Park and Yellowstone National Park before taking their granddaughter to Disney World in the fall. “When they told me I was cancer-free, it was just like someone said, ‘You won the lottery,'” he says. “If somebody else with this disease has the chance to walk in my shoes and live past it, that would be the greatest gift for me.”

new-chin-year-dragon-02

SPINY GRASS AND SCRAGGLY PINES creep amid the arts-and-crafts buildings of the Asilomar Conference Grounds, 100 acres of dune where California’s Monterey Peninsula hammerheads into the Pacific. It’s a rugged landscape, designed to inspire people to contemplate their evolving place on Earth. So it was natural that 140 scientists gathered here in 1975 for an unprecedented conference.

They were worried about what people called “recombinant DNA,” the manipulation of the source code of life. It had been just 22 years since James Watson, Francis Crick, and Rosalind Franklin described what DNA was—deoxyribonucleic acid, four different structures called bases stuck to a backbone of sugar and phosphate, in sequences thousands of bases long. DNA is what genes are made of, and genes are the basis of heredity.

Preeminent genetic researchers like David Baltimore, then at MIT, went to Asilomar to grapple with the implications of being able to decrypt and reorder genes. It was a God-like power—to plug genes from one living thing into another. Used wisely, it had the potential to save millions of lives. But the scientists also knew their creations might slip out of their control. They wanted to consider what ought to be off-limits.

By 1975, other fields of science—like physics—were subject to broad restrictions. Hardly anyone was allowed to work on atomic bombs, say. But biology was different. Biologists still let the winding road of research guide their steps. On occasion, regulatory bodies had acted retrospectively—after Nuremberg, Tuskegee, and the human radiation experiments, external enforcement entities had told biologists they weren’t allowed to do that bad thing again. Asilomar, though, was about establishing prospective guidelines, a remarkably open and forward-thinking move.

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At the end of the meeting, Baltimore and four other molecular biologists stayed up all night writing a consensus statement. They laid out ways to isolate potentially dangerous experiments and determined that cloning or otherwise messing with dangerous pathogens should be off-limits. A few attendees fretted about the idea of modifications of the human “germ line”—changes that would be passed on from one generation to the next—but most thought that was so far off as to be unrealistic. Engineering microbes was hard enough. The rules the Asilomar scientists hoped biology would follow didn’t look much further ahead than ideas and proposals already on their desks.

Earlier this year, Baltimore joined 17 other researchers for another California conference, this one at the Carneros Inn in Napa Valley. “It was a feeling of déjà vu,” Baltimore says. There he was again, gathered with some of the smartest scientists on earth to talk about the implications of genome engineering.

The stakes, however, have changed. Everyone at the Napa meeting had access to a gene-editing technique called Crispr-Cas9. The first term is an acronym for “clustered regularly interspaced short palindromic repeats,” a description of the genetic basis of the method; Cas9 is the name of a protein that makes it work. Technical details aside, Crispr-Cas9 makes it easy, cheap, and fast to move genes around—any genes, in any living thing, from bacteria to people. “These are monumental moments in the history of biomedical research,” Baltimore says. “They don’t happen every day.”

Using the three-year-old technique, researchers have already reversed mutations that cause blindness, stopped cancer cells from multiplying, and made cells impervious to the virus that causes AIDS. Agronomists have rendered wheat invulnerable to killer fungi like powdery mildew, hinting at engineered staple crops that can feed a population of 9 billion on an ever-warmer planet. Bioengineers have used Crispr to alter the DNA of yeast so that it consumes plant matter and excretes ethanol, promising an end to reliance on petrochemicals. Startups devoted to Crispr have launched. International pharmaceutical and agricultural companies have spun up Crispr R&D. Two of the most powerful universities in the US are engaged in a vicious war over the basic patent. Depending on what kind of person you are, Crispr makes you see a gleaming world of the future, a Nobel medallion, or dollar signs.

The technique is revolutionary, and like all revolutions, it’s perilous. Crispr goes well beyond anything the Asilomar conference discussed. It could at last allow genetics researchers to conjure everything anyone has ever worried they would—designer babies, invasive mutants, species-specific bioweapons, and a dozen other apocalyptic sci-fi tropes. It brings with it all-new rules for the practice of research in the life sciences. But no one knows what the rules are—or who will be the first to break them.

IN A WAY, humans were genetic engineers long before anyone knew what a gene was. They could give living things new traits—sweeter kernels of corn, flatter bulldog faces—through selective breeding. But it took time, and it didn’t always pan out. By the 1930s refining nature got faster. Scientists bombarded seeds and insect eggs with x-rays, causing mutations to scatter through genomes like shrapnel. If one of hundreds of irradiated plants or insects grew up with the traits scientists desired, they bred it and tossed the rest. That’s where red grapefruits came from, and most barley for modern beer.

Genome modification has become less of a crapshoot. In 2002, molecular biologists learned to delete or replace specific genes using enzymes called zinc-finger nucleases; the next-generation technique used enzymes named TALENs.

Yet the procedures were expensive and complicated. They only worked on organisms whose molecular innards had been thoroughly dissected—like mice or fruit flies. Genome engineers went on the hunt for something better.

Scientists have used it to render wheat invulnerable to killer fungi. Such crops could feed billions of people.

As it happened, the people who found it weren’t genome engineers at all. They were basic researchers, trying to unravel the origin of life by sequencing the genomes of ancient bacteria and microbes called Archaea (as in archaic), descendants of the first life on Earth. Deep amid the bases, the As, Ts, Gs, and Cs that made up those DNA sequences, microbiologists noticed recurring segments that were the same back to front and front to back—palindromes. The researchers didn’t know what these segments did, but they knew they were weird. In a branding exercise only scientists could love, they named these clusters of repeating palindromes Crispr.

Then, in 2005, a microbiologist named Rodolphe Barrangou, working at a Danish food company called Danisco, spotted some of those same palindromic repeats in Streptococcus thermophilus, the bacteria that the company uses to make yogurt and cheese. Barrangou and his colleagues discovered that the unidentified stretches of DNA between Crispr’s palindromes matched sequences from viruses that had infected their S. thermophilus colonies. Like most living things, bacteria get attacked by viruses—in this case they’re called bacteriophages, or phages for short. Barrangou’s team went on to show that the segments served an important role in the bacteria’s defense against the phages, a sort of immunological memory. If a phage infected a microbe whose Crispr carried its fingerprint, the bacteria could recognize the phage and fight back. Barrangou and his colleagues realized they could save their company some money by selecting S. thermophilus species with Crispr sequences that resisted common dairy viruses.

As more researchers sequenced more bacteria, they found Crisprs again and again—half of all bacteria had them. Most Archaea did too. And even stranger, some of Crispr’s sequences didn’t encode the eventual manufacture of a protein, as is typical of a gene, but instead led to RNA—single-stranded genetic material. (DNA, of course, is double-stranded.)

That pointed to a new hypothesis. Most present-day animals and plants defend themselves against viruses with structures made out of RNA. So a few researchers started to wonder if Crispr was a primordial immune system. Among the people working on that idea was Jill Banfield, a geomicrobiologist at UC Berkeley, who had found Crispr sequences in microbes she collected from acidic, 110-degree water from the defunct Iron Mountain Mine in Shasta County, California. But to figure out if she was right, she needed help.

Luckily, one of the country’s best-known RNA experts, a biochemist named Jennifer Doudna, worked on the other side of campus in an office with a view of the Bay and San Francisco’s skyline. It certainly wasn’t what Doudna had imagined for herself as a girl growing up on the Big Island of Hawaii. She simply liked math and chemistry—an affinity that took her to Harvard and then to a postdoc at the University of Colorado. That’s where she made her initial important discoveries, revealing the three-dimensional structure of complex RNA molecules that could, like enzymes, catalyze chemical reactions.

The mine bacteria piqued Doudna’s curiosity, but when Doudna pried Crispr apart, she didn’t see anything to suggest the bacterial immune system was related to the one plants and animals use. Still, she thought the system might be adapted for diagnostic tests.

Banfield wasn’t the only person to ask Doudna for help with a Crispr project. In 2011, Doudna was at an American Society for Microbiology meeting in San Juan, Puerto Rico, when an intense, dark-haired French scientist asked her if she wouldn’t mind stepping outside the conference hall for a chat. This was Emmanuelle Charpentier, a microbiologist at Ume˚a University in Sweden.

As they wandered through the alleyways of old San Juan, Charpentier explained that one of Crispr’s associated proteins, named Csn1, appeared to be extraordinary. It seemed to search for specific DNA sequences in viruses and cut them apart like a microscopic multitool. Charpentier asked Doudna to help her figure out how it worked. “Somehow the way she said it, I literally—I can almost feel it now—I had this chill down my back,” Doudna says. “When she said ‘the mysterious Csn1’ I just had this feeling, there is going to be something good here.”

Back in Sweden, Charpentier kept a colony of Streptococcus pyogenesin a biohazard chamber. Few people want S. pyogenes anywhere near them. It can cause strep throat and necrotizing fasciitis—flesh-eating disease. But it was the bug Charpentier worked with, and it was in S. pyogenes that she had found that mysterious yet mighty protein, now renamed Cas9. Charpentier swabbed her colony, purified its DNA, and FedExed a sample to Doudna.

Working together, Charpentier’s and Doudna’s teams found that Crispr made two short strands of RNA and that Cas9 latched onto them. The sequence of the RNA strands corresponded to stretches of viral DNA and could home in on those segments like a genetic GPS. And when the Crispr-Cas9 complex arrives at its destination, Cas9 does something almost magical: It changes shape, grasping the DNA and slicing it with a precise molecular scalpel.

Here’s what’s important: Once they’d taken that mechanism apart, Doudna’s postdoc, Martin Jinek, combined the two strands of RNA into one fragment—“guide RNA”—that Jinek could program. He could make guide RNA with whatever genetic letters he wanted; not just from viruses but from, as far as they could tell, anything. In test tubes, the combination of Jinek’s guide RNA and the Cas9 protein proved to be a programmable machine for DNA cutting. Compared to TALENs and zinc-finger nucleases, this was like trading in rusty scissors for a computer-controlled laser cutter. “I remember running into a few of my colleagues at Berkeley and saying we have this fantastic result, and I think it’s going to be really exciting for genome engineering. But I don’t think they quite got it,” Doudna says. “They kind of humored me, saying, ‘Oh, yeah, that’s nice.’”

On June 28, 2012, Doudna’s team published its results in Science. In the paper and in an earlier corresponding patent application, they suggest their technology could be a tool for genome engineering. It was elegant and cheap. A grad student could do it.

The finding got noticed. In the 10 years preceding 2012, 200 papers mentioned Crispr. By 2014 that number had more than tripled. Doudna and Charpentier were each recently awarded the $3 million 2015 Breakthrough Prize. Time magazine listed the duo among the 100 most influential people in the world. Nobody was just humoring Doudna anymore.

MOST WEDNESDAY AFTERNOONS, Feng Zhang, a molecular biologist at the Broad Institute of MIT and Harvard, scans the contents of Scienceas soon as they are posted online. In 2012, he was working with Crispr-Cas9 too. So when he saw Doudna and Charpentier’s paper, did he think he’d been scooped? Not at all. “I didn’t feel anything,” Zhang says. “Our goal was to do genome editing, and this paper didn’t do it.” Doudna’s team had cut DNA floating in a test tube, but to Zhang, if you weren’t working with human cells, you were just screwing around.

That kind of seriousness is typical for Zhang. At 11, he moved from China to Des Moines, Iowa, with his parents, who are engineers—one computer, one electrical. When he was 16, he got an internship at the gene therapy research institute at Iowa Methodist hospital. By the time he graduated high school he’d won multiple science awards, including third place in the Intel Science Talent Search.

When Doudna talks about her career, she dwells on her mentors; Zhang lists his personal accomplishments, starting with those high school prizes. Doudna seems intuitive and has a hands-off management style. Zhang … pushes. We scheduled a video chat at 9:15 pm, and he warned me that we’d be talking data for a couple of hours. “Power-nap first,” he said.

If new genes that wipe out malaria also make mosquitoes go extinct, what will bats eat?

Zhang got his job at the Broad in 2011, when he was 29. Soon after starting there, he heard a speaker at a scientific advisory board meeting mention Crispr. “I was bored,” Zhang says, “so as the researcher spoke, I just Googled it.” Then he went to Miami for an epigenetics conference, but he hardly left his hotel room. Instead Zhang spent his time reading papers on Crispr and filling his notebook with sketches on ways to get Crispr and Cas9 into the human genome. “That was an extremely exciting weekend,” he says, smiling.

Just before Doudna’s team published its discovery in Science, Zhang applied for a federal grant to study Crispr-Cas9 as a tool for genome editing. Doudna’s publication shifted him into hyperspeed. He knew it would prompt others to test Crispr on genomes. And Zhang wanted to be first.

Even Doudna, for all of her equanimity, had rushed to report her finding, though she hadn’t shown the system working in human cells. “Frankly, when you have a result that is exciting,” she says, “one does not wait to publish it.”

In January 2013, Zhang’s team published a paper in Science showing how Crispr-Cas9 edits genes in human and mouse cells. In the same issue, Harvard geneticist George Church edited human cells with Crispr too. Doudna’s team reported success in human cells that month as well, though Zhang is quick to assert that his approach cuts and repairs DNA better.

That detail matters because Zhang had asked the Broad Institute and MIT, where he holds a joint appointment, to file for a patent on his behalf. Doudna had filed her patent application—which was public information—seven months earlier. But the attorney filing for Zhang checked a box on the application marked “accelerate” and paid a fee, usually somewhere between $2,000 and $4,000. A series of emails followed between agents at the US Patent and Trademark Office and the Broad’s patent attorneys, who argued that their claim was distinct.

A little more than a year after those human-cell papers came out, Doudna was on her way to work when she got an email telling her that Zhang, the Broad Institute, and MIT had indeed been awarded the patent on Crispr-Cas9 as a method to edit genomes. “I was quite surprised,” she says, “because we had filed our paperwork several months before he had.”

The Broad win started a firefight. The University of California amended Doudna’s original claim to overlap Zhang’s and sent the patent office a 114-page application for an interference proceeding—a hearing to determine who owns Crispr—this past April. In Europe, several parties are contesting Zhang’s patent on the grounds that it lacks novelty. Zhang points to his grant application as proof that he independently came across the idea. He says he could have done what Doudna’s team did in 2012, but he wanted to prove that Crispr worked within human cells. The USPTO may make its decision as soon as the end of the year.

The stakes here are high. Any company that wants to work with anything other than microbes will have to license Zhang’s patent; royalties could be worth billions of dollars, and the resulting products could be worth billions more. Just by way of example: In 1983 Columbia University scientists patented a method for introducing foreign DNA into cells, called cotransformation. By the time the patents expired in 2000, they had brought in $790 million in revenue.

It’s a testament to Crispr’s value that despite the uncertainty over ownership, companies based on the technique keep launching. In 2011 Doudna and a student founded a company, Caribou, based on earlier Crispr patents; the University of California offered Caribou an exclusive license on the patent Doudna expected to get. Caribou uses Crispr to create industrial and research materials, potentially enzymes in laundry detergent and laboratory reagents. To focus on disease—where the long-term financial gain of Crispr-Cas9 will undoubtedly lie—Caribou spun off another biotech company called Intellia Therapeutics and sublicensed the Crispr-Cas9 rights. Pharma giant Novartis has invested in both startups. In Switzerland, Charpentier cofounded Crispr Therapeutics. And in Cambridge, Massachusetts, Zhang, George Church, and several others founded Editas Medicine, based on licenses on the patent Zhang eventually received.

Thus far the four companies have raised at least $158 million in venture capital.

ANY GENE TYPICALLY has just a 50–50 chance of getting passed on. Either the offspring gets a copy from Mom or a copy from Dad. But in 1957 biologists found exceptions to that rule, genes that literally manipulated cell division and forced themselves into a larger number of offspring than chance alone would have allowed.

A decade ago, an evolutionary geneticist named Austin Burt proposed a sneaky way to use these “selfish genes.” He suggested tethering one to a separate gene—one that you wanted to propagate through an entire population. If it worked, you’d be able to drive the gene into every individual in a given area. Your gene of interest graduates from public transit to a limousine in a motorcade, speeding through a population in flagrant disregard of heredity’s traffic laws. Burt suggested using this “gene drive” to alter mosquitoes that spread malaria, which kills around a million people every year. It’s a good idea. In fact, other researchers are already using other methods to modify mosquitoes to resist the Plasmodium parasite that causes malaria and to be less fertile, reducing their numbers in the wild. But engineered mosquitoes are expensive. If researchers don’t keep topping up the mutants, the normals soon recapture control of the ecosystem.

Push those modifications through with a gene drive and the normal mosquitoes wouldn’t stand a chance. The problem is, inserting the gene drive into the mosquitoes was impossible. Until Crispr-Cas9 came along.

Today, behind a set of four locked and sealed doors in a lab at the Harvard School of Public Health, a special set of mosquito larvae of the African species Anopheles gambiae wriggle near the surface of shallow tubs of water. These aren’t normal Anopheles, though. The lab is working on using Crispr to insert malaria-resistant gene drives into their genomes. It hasn’t worked yet, but if it does … well, consider this from the mosquitoes’ point of view. This project isn’t about reengineering one of them. It’s about reengineering them all.

Kevin Esvelt, the evolutionary engineer who initiated the project, knows how serious this work is. The basic process could wipe out any species. Scientists will have to study the mosquitoes for years to make sure that the gene drives can’t be passed on to other species of mosquitoes. And they want to know what happens to bats and other insect-eating predators if the drives make mosquitoes extinct. “I am responsible for opening a can of worms when it comes to gene drives,” Esvelt says, “and that is why I try to ensure that scientists are taking precautions and showing themselves to be worthy of the public’s trust—maybe we’re not, but I want to do my damnedest to try.”

Esvelt talked all this over with his adviser—Church, who also worked with Zhang. Together they decided to publish their gene-drive idea before it was actually successful. They wanted to lay out their precautionary measures, way beyond five nested doors. Gene drive research, they wrote, should take place in locations where the species of study isn’t native, making it less likely that escapees would take root. And they also proposed a way to turn the gene drive off when an engineered individual mated with a wild counterpart—a genetic sunset clause. Esvelt filed for a patent on Crispr gene drives, partly, he says, to block companies that might not take the same precautions.

Within a year, and without seeing Esvelt’s papers, biologists at UC San Diego had used Crispr to insert gene drives into fruit flies—they called them “mutagenic chain reactions.” They had done their research in a chamber behind five doors, but the other precautions weren’t there.Church said the San Diego researchers had gone “a step too far”—big talk from a scientist who says he plans to use Crispr to bring back an extinct woolly mammoth by deriving genes from frozen corpses and injecting them into elephant embryos. (Church says tinkering with one woolly mammoth is way less scary than messing with whole populations of rapidly reproducing insects. “I’m afraid of everything,” he says. “I encourage people to be as creative in thinking about the unintended consequences of their work as the intended.”)

Ethan Bier, who worked on the San Diego fly study, agrees that gene drives come with risks. But he points out that Esvelt’s mosquitoes don’t have the genetic barrier Esvelt himself advocates. (To be fair, that would defeat the purpose of a gene drive.) And the ecological barrier, he says, is nonsense. “In Boston you have hot and humid summers, so sure, tropical mosquitoes may not be native, but they can certainly survive,” Bier says. “If a pregnant female got out, she and her progeny could reproduce in a puddle, fly to ships in the Boston Harbor, and get on a boat to Brazil.”

These problems don’t end with mosquitoes. One of Crispr’s strengths is that it works on every living thing. That kind of power makes Doudna feel like she opened Pandora’s box. Use Crispr to treat, say, Huntington’s disease—a debilitating neurological disorder—in the womb, when an embryo is just a ball of cells? Perhaps. But the same method could also possibly alter less medically relevant genes, like the ones that make skin wrinkle. “We haven’t had the time, as a community, to discuss the ethics and safety,” Doudna says, “and, frankly, whether there is any real clinical benefit of this versus other ways of dealing with genetic disease.”

Researchers in China announced they had used Crispr to edit human embryos.

That’s why she convened the meeting in Napa. All the same problems of recombinant DNA that the Asilomar attendees tried to grapple with are still there—more pressing now than ever. And if the scientists don’t figure out how to handle them, some other regulatory body might. Few researchers, Baltimore included, want to see Congress making laws about science. “Legislation is unforgiving,” he says. “Once you pass it, it is very hard to undo.”

In other words, if biologists don’t start thinking about ethics, the taxpayers who fund their research might do the thinking for them.

All of that only matters if every scientist is on board. A month after the Napa conference, researchers at Sun Yat-sen University in Guangzhou, China, announced they had used Crispr to edit human embryos. Specifically they were looking to correct mutations in the gene that causes beta thalassemia, a disorder that interferes with a person’s ability to make healthy red blood cells.

The work wasn’t successful—Crispr, it turns out, didn’t target genes as well in embryos as it does in isolated cells. The Chinese researchers tried to skirt the ethical implications of their work by using nonviable embryos, which is to say they could never have been brought to term. But the work attracted attention. A month later, the US National Academy of Sciences announced that it would create a set of recommendations for scientists, policymakers, and regulatory agencies on when, if ever, embryonic engineering might be permissible. Another National Academy report will focus on gene drives. Though those recommendations don’t carry the weight of law, federal funding in part determines what science gets done, and agencies that fund research around the world often abide by the academy’s guidelines.

CRISPR/Cas9 and Targeted Genome Editing: A New Era in Molecular Biology

crispr new tools

The development of efficient and reliable ways to make precise, targeted changes to the genome of living cells is a long-standing goal for biomedical researchers. Recently, a new tool based on a bacterial CRISPR-associated protein-9 nuclease (Cas9) from Streptococcus pyogenes has generated considerable excitement (1). This follows several attempts over the years to manipulate gene function, including homologous recombination (2) and RNA interference (RNAi) (3). RNAi, in particular, became a laboratory staple enabling inexpensive and high-throughput interrogation of gene function (4, 5), but it is hampered by providing only temporary inhibition of gene function and unpredictable off-target effects (6). Other recent approaches to targeted genome modification – zinc-finger nucleases [ZFNs, (7)] and transcription-activator like effector nucleases [TALENs (8)]– enable researchers to generate permanent mutations by introducing doublestranded breaks to activate repair pathways. These approaches are costly and time-consuming to engineer, limiting their widespread use, particularly for large scale, high-throughput studies.

The Biology of Cas9

The functions of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and CRISPR-associated (Cas) genes are essential in adaptive immunity in select bacteria and archaea, enabling the organisms to respond to and eliminate invading genetic material. These repeats were initially discovered in the 1980s in E. coli (9), but their function wasn’t confirmed until 2007 by Barrangou and colleagues, who demonstrated that S. thermophilus can acquire resistance against a bacteriophage by integrating a genome fragment of an infectious virus into its CRISPR locus (10).

Three types of CRISPR mechanisms have been identified, of which type II is the most studied. In this case, invading DNA from viruses or plasmids is cut into small fragments and incorporated into a CRISPR locus amidst a series of short repeats (around 20 bps). The loci are transcribed, and transcripts are then processed to generate small RNAs (crRNA – CRISPR RNA), which are used to guide effector endonucleases that target invading DNA based on sequence complementarity (Figure 1) (11).

Figure 1. Cas9 in vivo: Bacterial Adaptive Immunity

In the acquisition phase, foreign DNA is incorporated into the bacterial genome at the CRISPR loci. CRISPR loci is then transcribed and processed into crRNA during crRNA biogenesis. During interference, Cas9 endonuclease complexed with a crRNA and separate tracrRNA cleaves foreign DNA containing a 20-nucleotide crRNA complementary sequence adjacent to the PAM sequence. (Figure not drawn to scale.)

One Cas protein, Cas9 (also known as Csn1), has been shown, through knockdown and rescue experiments to be a key player in certain CRISPR mechanisms (specifically type II CRISPR systems). The type II CRISPR mechanism is unique compared to other CRISPR systems, as only one Cas protein (Cas9) is required for gene silencing (12). In type II systems, Cas9 participates in the processing of crRNAs (12), and is responsible for the destruction of the target DNA (11). Cas9’s function in both of these steps relies on the presence of two nuclease domains, a RuvC-like nuclease domain located at the amino terminus and a HNH-like nuclease domain that resides in the mid-region of the protein (13).

To achieve site-specific DNA recognition and cleavage, Cas9 must be complexed with both a crRNA and a separate trans-activating crRNA (tracrRNA or trRNA), that is partially complementary to the crRNA (11). The tracrRNA is required for crRNA maturation from a primary transcript encoding multiple pre-crRNAs. This occurs in the presence of RNase III and Cas9 (12).

During the destruction of target DNA, the HNH and RuvC-like nuclease domains cut both DNA strands, generating double-stranded breaks (DSBs) at sites defined by a 20-nucleotide target sequence within an associated crRNA transcript (11, 14). The HNH domain cleaves the complementary strand, while the RuvC domain cleaves the noncomplementary strand.

The double-stranded endonuclease activity of Cas9 also requires that a short conserved sequence, (2–5 nts) known as protospacer-associated motif (PAM), follows immediately 3´- of the crRNA complementary sequence (15). In fact, even fully complementary sequences are ignored by Cas9-RNA in the absence of a PAM sequence (16).

Cas9 and CRISPR as a New Tool in Molecular Biology

The simplicity of the type II CRISPR nuclease, with only three required components (Cas9 along with the crRNA and trRNA) makes this system amenable to adaptation for genome editing. This potential was realized in 2012 by the Doudna and Charpentier labs (11). Based on the type II CRISPR system described previously, the authors developed a simplified two-component system by combining trRNA and crRNA into a single synthetic single guide RNA (sgRNA). sgRNAprogrammed Cas9 was shown to be as effective as Cas9 programmed with separate trRNA and crRNA in guiding targeted gene alterations (Figure 2A).

To date, three different variants of the Cas9 nuclease have been adopted in genome-editing protocols. The first is wild-type Cas9, which can site-specifically cleave double-stranded DNA, resulting in the activation of the doublestrand break (DSB) repair machinery. DSBs can be repaired by the cellular Non-Homologous End Joining (NHEJ) pathway (17), resulting in insertions and/or deletions (indels) which disrupt the targeted locus. Alternatively, if a donor template with homology to the targeted locus is supplied, the DSB may be repaired by the homology-directed repair (HDR) pathway allowing for precise replacement mutations to be made (Figure 2A) (17, 18).

Cong and colleagues (1) took the Cas9 system a step further towards increased precision by developing a mutant form, known as Cas9D10A, with only nickase activity. This means it cleaves only one DNA strand, and does not activate NHEJ. Instead, when provided with a homologous repair template, DNA repairs are conducted via the high-fidelity HDR pathway only, resulting in reduced indel mutations (1, 11, 19). Cas9D10A is even more appealing in terms of target specificity when loci are targeted by paired Cas9 complexes designed to generate adjacent DNA nicks (20) (see further details about “paired nickases” in Figure 2B).

The third variant is a nuclease-deficient Cas9 (dCas9, Figure 2C) (21). Mutations H840A in the HNH domain and D10A in the RuvC domain inactivate cleavage activity, but do not prevent DNA binding (11, 22). Therefore, this variant can be used to sequence-specifically target any region of the genome without cleavage. Instead, by fusing with various effector domains, dCas9 can be used either as a gene silencing or activation tool (21, 23–26). Furthermore, it can be used as a visualization tool. For instance, Chen and colleagues used dCas9 fused to Enhanced Green Fluorescent Protein (EGFP) to visualize repetitive DNA sequences with a single sgRNA or nonrepetitive loci using multiple sgRNAs (27).

Figure 2. CRISPR/Cas9 System Applications

A. Wild-type Cas9 nuclease site specifically cleaves double-stranded DNA activating double-strand break repair machinery. In the absence of a homologous repair template non-homologous end joining can result in indels disrupting the target sequence. Alternatively, precise mutations and knock-ins can be made by providing a homologous repair template and exploiting the homology directed repair pathway.
B. Mutated Cas9 makes a site specific single-strand nick. Two sgRNA can be used to introduce a staggered double-stranded break which can then undergo homology directed repair.
C. Nuclease-deficient Cas9 can be fused with various effector domains allowing specific localization. For example, transcriptional activators, repressors, and fluorescent proteins.

Targeting Efficiency and Off-target Mutations

Targeting efficiency, or the percentage of desired mutation achieved, is one of the most important parameters by which to assess a genome-editing tool. The targeting efficiency of Cas9 compares favorably with more established methods, such as TALENs or ZFNs (8). For example, in human cells, custom-designed ZFNs and TALENs could only achieve efficiencies ranging from 1% to 50% (29–31). In contrast, the Cas9 system has been reported to have efficiencies up to >70% in zebrafish (32) and plants (33), and ranging from 2–5% in induced pluripotent stem cells (34). In addition, Zhou and colleagues were able to improve genome targeting up to 78% in one-cell mouse embryos, and achieved effective germline transmission through the use of dual sgRNAs to simultaneously target an individual gene (35).

A widely used method to identify mutations is the T7 Endonuclease I mutation detection assay (36, 37) (Figure 3). This assay detects heteroduplex DNA that results from the annealing of a DNA strand, including desired mutations, with a wildtype DNA strand (37).

Figure 3. T7 Endonuclease I Targeting Efficiency Assay

Genomic DNA is amplified with primers bracketing the modified locus. PCR products are then denatured and re-annealed yielding 3 possible structures. Duplexes containing a mismatch are digested by T7 Endonuclease I. The DNA is then electrophoretically separated and fragment analysis is used to calculate targeting efficiency.

Another important parameter is the incidence of off-target mutations. Such mutations are likely to appear in sites that have differences of only a few nucleotides compared to the original sequence, as long as they are adjacent to a PAM sequence. This occurs as Cas9 can tolerate up to 5 base mismatches within the protospacer region (36) or a single base difference in the PAM sequence (38). Off-target mutations are generally more difficult to detect, requiring whole-genome sequencing to rule them out completely.

Recent improvements to the CRISPR system for reducing off-target mutations have been made through the use of truncated gRNA (truncated within the crRNA-derived sequence) or by adding two extra guanine (G) nucleotides to the 5´ end (28, 37). Another way researchers have attempted to minimize off-target effects is with the use of “paired nickases” (20). This strategy uses D10A Cas9 and two sgRNAs complementary to the adjacent area on opposite strands of the target site (Figure 2B). While this induces DSBs in the target DNA, it is expected to create only single nicks in off-target locations and, therefore, result in minimal off-target mutations.

By leveraging computation to reduce off-target mutations, several groups have developed webbased tools to facilitate the identification of potential CRISPR target sites and assess their potential for off-target cleavage. Examples include the CRISPR Design Tool (38) and the ZiFiT Targeter, Version 4.2 (39, 40).

Applications as a Genome-editing and Genome Targeting Tool

Following its initial demonstration in 2012 (9), the CRISPR/Cas9 system has been widely adopted. This has already been successfully used to target important genes in many cell lines and organisms, including human (34), bacteria (41), zebrafish (32), C. elegans (42), plants (34), Xenopus tropicalis (43), yeast (44), Drosophila(45), monkeys (46), rabbits (47), pigs (42), rats (48) and mice (49). Several groups have now taken advantage of this method to introduce single point mutations (deletions or insertions) in a particular target gene, via a single gRNA (14, 21, 29). Using a pair of gRNA-directed Cas9 nucleases instead, it is also possible to induce large deletions or genomic rearrangements, such as inversions or translocations (50). A recent exciting development is the use of the dCas9 version of the CRISPR/Cas9 system to target protein domains for transcriptional regulation (26, 51, 52), epigenetic modification (25), and microscopic visualization of specific genome loci (27).

The CRISPR/Cas9 system requires only the redesign of the crRNA to change target specificity. This contrasts with other genome editing tools, including zinc finger and TALENs, where redesign of the protein-DNA interface is required. Furthermore, CRISPR/Cas9 enables rapid genome-wide interrogation of gene function by generating large gRNA libraries (51, 53) for genomic screening.

The future of CRISPR/Cas9

The rapid progress in developing Cas9 into a set of tools for cell and molecular biology research has been remarkable, likely due to the simplicity, high efficiency and versatility of the system. Of the designer nuclease systems currently available for precision genome engineering, the CRISPR/Cas system is by far the most user friendly. It is now also clear that Cas9’s potential reaches beyond DNA cleavage, and its usefulness for genome locus-specific recruitment of proteins will likely only be limited by our imagination.

new-chin-year-dragon-02

Jakarta detik – Ilmuwan Amerika Serikat (AS) kini telah berhasil membikin genom (kumpulan gen) terkecil yang bisa hidup. Genom ini terdiri dari gen-gen dasar yang diperlukan bagi organisme untuk berfungsi dan bereproduksi sendiri.

Sebagaimana dilansir AFP, Sabtu (26/3/2016), ini adalah langkah besar menyibak misteri bagaimana kehidupan diciptakan. Genom sintetis dari bakteria ini punya julukan JCVI-syn3.0. Bakteri bikinan manusia ini hanya terdiri dari 473 gen, bandingkan dengan yang dipunya manusia, yakni terdiri dari 20.000 gen.

Pimpinan penelitian ini, Craig Venter, adalah orang pertama yang bisa menguraikan kode genom manusia. Selain Craig Venter, ada pula Clyde Hutchinson yang memimpin penelitian ini.

Meski begitu, tim ilmuwan ini belum menentukan fungsi dari 149 gen alias sepertiga dari total gen-gen yang mereka gabungkan itu. “Tugas pertama para investigator adalah menyelidiki aturan main gen-gen ini. Tugas ini menjanjikan pemahaman baru atas dasar kehidupan biologis,” kata Chris Voigt, ahli biologi sintetis dari Massachusetts Institute of Technology yang tak berpartisipasi dalam penelitian itu.

Sejumlah gen potensial yang berkesesuaian telah ditemukan di organisme lain. Ini mendorong mereka untuk mengkode protein universal dengan fungsi yang sampai sekarang masih belum bisa dipastikan.

Para peneliti itu menggunakan proses tes rancangan untuk mengidentifikasi gen quasi-esensial (gen yang sebenarnya tidak punya peran penting). Gen quasi-esensial itu dibutuhkan untuk pertumbuhan yang sehat, namun bukan untuk kehidupan.

Studi ini dipublikasikan pada jurnal ‘Science’ edisi Kamis (24/3). Melalui serangkaian eksperimen, mereka mencapai genom sintetis yang tereduksi, dibikin sekecil mungkin untuk menjamin tak ada lagi gen yang bisa mengacaukan genom ini.

Langkah Penting

“Satu-satunya  cara untuk menjawab pertanyaan mendasar tentang hidup adalah dengan cara mendapatkan genom paling minimal,” kata Craig Venter melalui telekonferensi.

“Mungkin satu-satunya jalan untuk melakukan itu adalah mencoba mensintesiskan (membikin -red) sebuah genom,” imbuh Venter.

24-Mar-2016                                        kehidupan sintetis

First Minimal Synthetic Bacterial Cell Designed and Constructed by Scientists at Venter Institute and Synthetic Genomics, Inc.

Cell, JCVI-syn3.0, was minimized to just 473 genes

(LA JOLLA, CA)—March 24, 2016—Researchers from the J. Craig Venter Institute (JCVI) and Synthetic Genomics, Inc. (SGI) announced today the design and construction of the first minimal synthetic bacterial cell, JCVI-syn3.0.

Using the first synthetic cell, Mycoplasma mycoides JCVI-syn1.0 (created by this same team in 2010), JCVI-syn3.0 was developed through a design, build, and test process using genes from JCVI-syn1.0. The new minimal synthetic cell contains 531,560 base pairs and just 473 genes, making it the smallest genome of any organism that can be grown in laboratory media. Of these genes 149 are of unknown biological function. By comparison the first synthetic cell, M. mycoides JCVI-syn1.0 has 1.08 million base pairs and 901 genes.

A paper describing this research is being published in the March 25th print version of the journal Science by lead authors Clyde A. Hutchison, III, Ph.D. and Ray-Yuan Chuang, Ph.D., senior author J. Craig Venter, Ph.D., and senior team of Hamilton O. Smith, MD, Daniel G. Gibson, Ph.D., and John I. Glass, Ph.D.

“Our attempt to design and create a new species, while ultimately successful, revealed that 32% of the genes essential for life in this cell are of unknown function, and showed that many are highly conserved in numerous species. All the bioinformatics studies over the past 20 years have underestimated the number of essential genes by focusing only on the known world. This is an important observation that we are carrying forward into the study of the human genome,” said Dr. Venter, Founder, Executive Chairman, and CEO, JCVI.

The research to construct the first minimal synthetic cell at JCVI was the culmination of 20 years of research that began in 1995 after the genome sequencing of the first free-living organism, Haemophilus influenza, followed by the sequencing of Mycoplasma genitalium. A comparison of these two genomes revealed a common set of 256 genes which the team thought could be a minimal set of genes needed for viability. In 1999 Dr. Hutchison led a team who published a paper describing the use of global transposon mutagenesis techniques to identify the nonessential genes in M. genitalium.

Over the last 50 years more than 2,000 publications have contemplated minimal cells and their use in elucidating first principals of biology. From the start, the goal of the JCVI team was similar—build a minimal operating system of a cell to understand biology but to also have a desirable chassis for use in industrial applications. The creation of the first synthetic cell in 2010 did not inform new genome design principles since the M. mycoides genome was mostly recapitulated as in nature.  Rather, it established a work flow for building and testing whole genome designs, including a minimal cell, from the bottom up starting from a genome sequence.

To create JCVI-syn3.0, the team used an approach of whole genome design and chemical synthesis followed by genome transplantation to test if the cell was viable. Their first attempt to minimize the genome began with a simple approach using information in the biochemical literature and some limited transposon mutagenesis work, but this did not result in a viable genome. After improving transposon methods, they discovered a set of quasi-essential genes that are necessary for robust growth which explained the failure of their first attempt.

To facilitate debugging of non-functional reduced genome segments, the team built the genome in eight segments at a time so that each could be tested separately before combining them to generate a minimal genome. The team also explored gene order and how that affects cell growth and viability, noting that gene content was more critical to cell viability than gene order. They went through three cycles of designing, building, and testing ensuring that the quasi-essential genes remained, which in the end resulted in a viable, self-replicating minimal synthetic cell that contained just 473 genes, 35 of which are RNA-coding. In addition, the cell contains a unique 16S gene sequence.

The team was able to assign biological function to the majority of the genes with 41% of them responsible for genome expression information, 18% related to cell membrane structure and function, 17% related to cytosolic metabolism, and 7% preservation of genome information. However, a surprising 149 genes could not be assigned a specific biological function despite intensive study. This remains an area of continued work for the researchers.

“This paper represents more than five years of work by an amazingly talented group of people. Our goal is to have a cell for which the precise biological function of every gene is known,” said Dr. Hutchison, Distinguished Professor, JCVI.

The team concludes that a major outcome of this minimal cell program are new tools and semi-automated processes for whole genome synthesis.  Many of these synthetic biology tools and services are commercially available through SGI and SGI-DNA including a synthetic DNA construction service specializing in building large and complex DNA fragments including combinatorial gene libraries, Archetype® genomics software, Gibson Assembly® kits, and the BioXp™, which is a benchtop instrument for producing accurate synthetic DNA fragments.

“This paper signifies a major step toward our ability to design and build synthetic organisms from the bottom up with predictable outcomes.  The tools and knowledge gained from this work will be essential to producing next generation production platforms for a wide range of disciplines,” said Dr. Gibson, Vice President, DNA Technologies, SGI; Associate Professor, JCVI.

The other researchers on this paper have been integral to this work for much of the last decade. Current and former JCVI and SGI scientists are: Chuck Merryman, Ph.D., Ray-Yuan Chuang, Ph.D., Vladimir Noskov, Ph.D., Nacyra Assad-Garcia, John Gill, Krishna Kannan, Ph.D., Bogumil Karas, Ph.D., Li Ma, Zhi-Qing Qi, Ph.D., R. Alexander Richter, Ph.D., Lijie Sun, Ph.D., Yo Suzuki, Ph.D., Billyana Tsvetanova, Ph.D. and Kim Wise, Ph.D.

Other authors on the paper are: Thomas J. Deerinck and Mark H. Ellisman, Ph.D., University of California, San Diego National Center for Microscopy and Imaging Research; James F. Pelletier, Center for Bits and Atoms and Department of Physics, Massachusetts Institute of Technology; Elizabeth A. Strychalski, National Institute of Standards and Technology.

This work was funded by SGI, the JCVI endowment and the Defense Advanced Research Projects Agency’s Living Foundries program, HR0011-12-C-0063.

About J. Craig Venter Institute

The JCVI is a not-for-profit research institute in Rockville, MD and La Jolla, CA dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 200 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The JCVI is a 501 (c)(3) organization. For additional information, please visit http://www.JCVI.org.

JCVI Media Contact

Heather Kowalski, hkowalski(AT)jcvi.org

– See more at: http://www.jcvi.org/cms/press/press-releases/full-text/article/first-minimal-synthetic-bacterial-cell-designed-and-constructed-by-scientists-at-venter-institute-an/#sthash.kTm3YrGS.dpuf

rose KECIL

DNA Robots Programmed to Kill Cancer Cells, Harvard Study Shows

Usaha ini mengantarkan ilmuwan kepada Mycoplasma, yakni bakteri dengan sel genom terkecil. Mycoplasma dapat mereplikasi (menggandakan) dirinya sendiri secara otonom.

“Bila Anda tak tahu apapun soal pesawat terbang dan Anda sedang melihat Boeing 777, dan Anda cuma mencari tahu fungsi bagian-bagian pesawat itu dengan cara mengurainya, dan anda mempreteli mesinnya dari sayap kanan, pesawat itu masih bisa terbang dan mendarat,” kata Venter mencoba menjelaskan dengan analogi.

“Jadi mungkin Anda mengatakan ini adalah komponen yang tidak penting, dan Anda tak benar-benar menemukan hal yang paling esensial sampai anda mempreteli (mesin pesawat) yang satunya lagi. Dan itulah yang terjadi, lagi dan lagi, pada biologi saat kami akan mendapati komponen yang non-esensial, sampai pada saat kita mempreteli pasangannya,” kata Venter.

Pada satu penemuan penting, tim peneliti belajar bahwa beberapa gen digolongkan sebagai ‘non-esensial (tidak penting)’. Artinya, gen satunya lagi adalah gen yang wajib diperlukan, alias gen yang ‘esensial’, atau gen minimal yang dibutuhkan.

Genom minimal tak punya gen yang bisa memodifikasi dan membatasi DNA. Genom minimal juga kurang akan gen yang mengkode lipoprotein.

Bagaimanapun juga, ‘genom minimalis’ ini mengandung semua gen yang diperlukan dalam pembacaan dan mengekspresikan informasi genetik dalam genom, sebagaimana dalam hal menjaga informasi genetik dari generasi ke generasi.

(dnu/dnu)

animated-rocket-and-space-shuttle-image-0026

By Elizabeth Lopatto – Feb 16, 2012

Scientists have created a robot made entirely from DNA that can be instructed to find diseased cells in the body and deliver a payload to kill or reprogram them, according to a study from Harvard University.

The robot was constructed by folding DNA strands into a shape that looks roughly like a clamshell. The researchers programmed the nano-sized device to open in the presence of leukemia and lymphoma cells in a laboratory dish, where they delivered immune system antibodies that caused the cells to self-destruct, according to a report in the journal Science.

The next step will be to test the system in animals, tweaking the robot so that it can circulate longer in the blood to locate all cancer cells. The technology isn’t yet ready for commercial use, said Shawn Douglas, an author of the study.

“In diseases such as cancer we know if we can find every single last cell and kill or reprogram it, we can cure that disease,” said Douglas, a researcher at the Wyss Institute for Biologically Inspired Engineering at Harvard, in Boston. “A lot of our current therapies fall short.”

The idea is based on the behavior of the body’s immune cells, which recognize viruses or other invaders and attack them, Douglas said. The DNA nano-robots, with similar capabilities, may potentially lead to the development of new types of targeted cancer treatments that kill only abnormal cells, he said.

The robots don’t reproduce. They have to be constructed in a process that has gained traction since the idea of DNA nanotechnology was first suggested in 1982.
Genetic Information

DNA is a material, shaped in the form of a revolving ladder, which carries the genetic information in our cells.

The double-sided strands have so-called sticky ends that allow them to be joined together with other DNA. Scientists, led by Nadrian Seeman, now head of the Department of Chemistry at New York University, have used those sticky ends to form DNA into lattices that can be shaped in various ways.

The latest research created a robot in a clamshell shape that’s held together with a “zipper” constructed of a special sequence of DNA, the report said. The zipper was programmed to release its grip when it recognized specific targets on a cell, allowing the robot to release its payload.

In the experiment, Douglas and his fellow scientists used the robot they constructed to deliver instructions encoded in antibodies to the cancer cells.

“It’s an important step forward in specific targeting,” said Milan Stojanovic, an assistant professor of experimental therapeutics at Columbia University in New York who wasn’t involved in the research, in an e-mail. “It looks very exciting.”

Besides cancer, the robots may also benefit people with autoimmune disease, Douglas said. One day, the robots might be used to find immune cells wrongly attacking the body and reprogram them, he said.

Juli 20, 2017

masa gitu sih: ftalat itu racun

Filed under: Medicine — bumi2009fans @ 5:36 pm

Bisnis.com, JAKARTA–Beredarnya kabar kandungan zat kimia untuk memproduksi plastik, phthalate yang terkandung pada makanan Mac and Cheese instan cukup mengkhawatirkan.

Hal ini disebabkan bahwa phthalate diduga dapat berdampak pada sistem reproduksi dan bersifat karsinogenik.

Sejatinya, phthalate digunakan digunakan sebagai bahan aditif yang berfungsi melunakkan polivinil klorida (PVC) dan membuatnya menjadi fleksibel.

Zat ini banyak digunakan untuk pembuatan mainan anak. Adapun jenis lainnya juga digunakan pada parfum dan berbagai produk perawatan kecantikan.

Ahli gizi Rita Ramayulis menjelaskan bahwa phthalate adalah zat kimia yang berfungsi untuk menciptakan tekstur pada bahan-bahan seperti plastik.

Artinya, zat ini bukan zat tambahan makanan. Kalaupun terkandung dalam makanan , perlu ada batas toleransinya.

Menilik dampaknya jika zat tersebut dikonsumsi dan masuk ke dalam tubuh, Rita mengatakan zat ini akan keluar dari tubuh secara alami melalui urin.

“Namun, beberapa jurnal menjelaskan bahwa zat ini akan mengendap dalam tubuh manusia. Jika mengendap pada tubuh anak laki-laki yang hormon testosteronnya sedang berkembang maka jumlah hormon testosteronnya bisa berkurang,” ujarnya kepada Bisnis.com, Kamis (20/7/2017).

Bahkan pada penelitian lain, lanjutnya, jika masuk ke dalam tubuh ibu hamil dengan jani laki-laki, zat phthalate akan menghambat pembentukan sifat anak laki-laki.

Selain itu, jurnal Laon menjelaskan adanya sifat karsinogenik setelah paparan ini semakin meningkat dan makanan dan mainan anak, serta benda plastik lainnya.

“Dosis amannya belum ditetapkan dan masih menjadi perdebatan. Namun, Uni Eropa pernah menetapkan batas aman penggunaan phthalate untuk produk mainan yang terbuat dari plastik sebesar 0,1% saja,” katanya.

Sebelumnya, beberapa media di luar negeri mencuatkan berita terkait penemuam zat phthalate dalam produkMac and Cheese keluaran produsen ternama seperti Kraft Heinz.

Reuters mencatat bahwa zat kimia yang ditemukan di dalam botol plastik, makanan kaleng, deterjen, osmetika dan pestisida telah membengkakkan biaya kesehatan di Amerika Serikat hingga US$340 miliar atau dua kali lebih besar dari biaya Uni Eropa dalam setahun.

Peneliti kesehatan masyarakat di Universitas Harvard menyarankan untuk mengindari makanan yang dipanaskan dengan microwave di dalam wadah plastik, makanan kaleng, dan makanan yang menggunakan wadah plastik lainnya.

“Masyarakat juga perlu menghindari penggunaan wadah plastik dengan label bernomor 3,6, 7 karena mengandung zat kimia seperti phthalate. Beralih ke bahan-bhan natural atau bebas wewangian pada kosmetika bisa mencegah dari paparan penyakit,” ujarnya.

 

Juli 11, 2017

Sekali Lagi: bau mulut n kopi

Filed under: Medicine — bumi2009fans @ 1:03 am

sumber tulisan

We tend to smell like the food we eat and the liquids we drink — what we eat and drink is digested in our stomachs and intestines, and the chemicals in these foods and liquids are passed on throughout our bodies through our bloodstreams. The stronger and more pungent the smell of the food or liquid, the stronger and more pungent our breath and body odor will be. Such odors will last until the food and liquid is completely processed and their remnants pass out of our bodies. The foods and liquids that cause the worst odors are those that include the highest sulfur compounds, such as coffee.

The caffeine in coffee can dry out your mouth by slowing saliva production, which can lead to bad breath. A lack of saliva causes bad breath for a couple of reasons. One is that saliva helps kill bacteria found in your mouth, and the other is that saliva helps you digest food particles caught in your teeth and other areas of your mouth. If there is no longer enough saliva in your mouth because of caffeine, then the bacteria that cause bad breath will grow out of control. Similarly, if your mouth isn’t producing enough saliva to digest the food particles caught in your teeth, bacteria will begin to break down those food particles, giving off bad odors in the process. Coffee is worse than usual in this regard because of its sulfurous content, which certain bad breath-causing bacteria can break down to produce odor.

One final reason that drinking coffee can give you bad breath is simply that coffee has a very strong odor that smells worse than it tastes. Combined with the other bad-smelling odors, this can result in terrible smelling breath. It is also possible that other compounds such as milk in the coffee you drink contribute to the problem.

Maret 27, 2017

gadis genit: syarat BERLAKU, PISANk bwat otak n jantung … 070411_270317

Filed under: Medicine — bumi2009fans @ 12:03 am

Potassium intake for adults and children

Guidance summary*

WHO recommendations

WHO recommends an increase in potassium intake from food to reduce blood pressure and risk of cardiovascular disease, stroke and coronary heart disease in adults. WHO suggests a potassium intake of at least 90 mmol/day (3510 mg/day) for adults.

WHO suggests an increase in potassium intake from food to control** blood pressure in children aged 2–15 years. The recommended potassium intake of at least 90 mmol/day in adults should be adjusted downward for children, based on the energy requirements of children relative to those of adults.

Remarks

  • For this recommendation, “adults” includes all individuals ≥16 years of age.
  • For this recommendation, “children” includes all individuals 2–15 years of age.
  • The recommendation for children does not address the recommended period of exclusive breastfeeding (0–6 months) or the period of complementary feeding with continued breastfeeding (6–24 months).
  • These recommendations apply to all individuals, with or without hypertension (including pregnant and lactating women) except for those with impaired urinary potassium excretion.
  • These recommendations do not address the optimal ratio of sodium to potassium; however, if this guideline and the WHO guideline on sodium consumption are achieved, the molar ratio of sodium to potassium would be approximately one to one. To maintain this molar ratio at higher levels of sodium consumption, the recommended level of intake of ≥90 mmol/day potassium should be increased.
  • These recommendations complement the WHO guideline on sodium consumption and should not be interpreted to replace or supersede that guideline. Public health interventions should aim to increase potassium intake through foods, and to simultaneously reduce sodium intake.
  • The recommended level of intake of ≥90 mmol/day is a conditional recommendation for adults because there is limited evidence regarding the precise level that will result in maximum health benefits. The recommendation is informed by moderate and high-quality evidence that consuming potassium at ≥90 mmol/day will provide a health benefit. However, the recommendation recognizes that the value may change if there are additional high-quality trials that determine the precise level of potassium intake that achieves the most favourable reduction in blood pressure and risk of cardiovascular disease, stroke and coronary heart disease, without a negative effect on other health outcomes such as blood lipids and catecholamine levels.
  • The recommendation to increase potassium intake in children is conditional, because few studies in children have considered the effects of increased potassium on blood pressure, blood lipids, catecholamine levels, and other possible adverse effects. The recommendation is based on a limited amount of low-quality direct evidence from children, and moderate-quality indirect evidence from adults. Because renal function is fully developed early in childhood, an adult population is an appropriate proxy population for informing guidelines for children. This recommendation recognizes that there is a need for high-quality RCTs, to verify the effects of potassium intake on blood pressure and potential adverse effects in children. An adjustment in intake, based on energy requirement, is recommended because the relatively high energy intake on a per body-weight basis during periods of rapid growth implies a risk that the recommended level of potassium intake could be too low if adjustments to the adult recommended value are made on a per body-weight basis. Every country should determine the requirement of various age categories of the paediatric population relative to adults 20–50 years of age, to adjust the recommended minimum intake value of 90 mmol/day. If country-specific data are not available, data from another country with similar population demographics and dietary habits can be used to make this adjustment.
  • These recommendations recognize that non-acclimated individuals engaged in intense physical activities (especially at high temperatures) for extended periods of time, resulting in the production of large volumes of sweat, should consume higher levels of potassium to replace potassium losses via sweat. For most individuals, sufficient potassium to replace such losses can be consumed through food, without the need for specially formulated food and beverage products.
  • It is recommended that potassium be consumed through food. Because of the safety of consumption of increased potassium via food, no upper limit has been considered.

* This is an extract from the relevant guideline (1). Additional guidance information can be found in this document.
** “Control” for this recommendation refers to the prevention of a deleterious rise in blood pressure with age.


References

1. WHO. Guideline: Potassium intake for adults and children. Geneva, World Health Organization; 2009 (http://www.who.int/nutrition/publications/guidelines/potassium_intake/en/).

long jump icon
TEMPO.CO, Tulungagung – Rumah Sakit Umum Daerah Dr Iskak Kabupaten Tulungagung dinobatkan menjadi rumah sakit pemerintah pertama yang memiliki fasilitas pemasangan ring jantung berstandar internasional. Selama ini penanganan serupa hanya dimiliki rumah sakit jantung swasta Harapan Kita di Jakarta.

Sejak dua bulan terakhir RSUD Dr Iskak Tulungagung telah memiliki layanan kateterisasi jantung di ruang gawat darurat. “Dalam hitungan menit, pasien serangan jantung bisa dideteksi titik penyumbatannya untuk dibuka melalui kateterisasi,” kata Ketua Perhimpunan Intervensi Kardiologi Indonesia (PIKI) Sunarya Soerianata, saat memboyong puluhan dokter jantung dari seluruh Indonesia ke Tulungagung, Sabtu 25 Maret 2017.

Baca:
Rokok Elektrik Tingkatkan Risiko Penyakit Jantung
Benarkah Disfungsi Ereksi Tanda Penyakit Jantung?

Layanan kateterisasi di ruang gawat darurat ini, menurut Sunarya, diklaim mampu menurunkan risiko kematian pasien jantung hingga 50 persen. Sebab potensi kematian pasien rata-rata dipengaruhi oleh keterlambatan penanganan yang rentang waktu dari serangan tak lebih 30 menit. Masa kritis melakukan tindakan penyelamatan inilah yang bisa diperpendek melalui layanan kateterisasi di ruang gawat darurat RSUD dr Iskak.

Dalam hitungan 3–5 menit, tim di ruang gawat darurat akan bisa merekam dan menemukan sumbatan, lalu membedah pembuluh darah yang tersumbat. “Kami berharap kelak seluruh rumah sakit pemerintah bisa melakukan ini,” ujar Sunarya.

Infrastruktur di ruang darurat rumah sakit, penyediaan tenaga medis yang sudah terlatih di tiap kecamatan juga menjadi kunci suksesnya terobosan ini. “Kami juga memiliki 40 mobil ambulan yang dilengkapi dengan tenaga, obat, dan peralatan jantung di dalamnya,” kata Direktur RSUD Dr Iskak, Supriyanto.

Maps of the lymphatic system: old (left) and updated to reflect UVA’s discovery.
Credit: University of Virginia Health System

science daily: In a stunning discovery that overturns decades of textbook teaching, researchers at the University of Virginia School of Medicine have determined that the brain is directly connected to the immune system by vessels previously thought not to exist. That such vessels could have escaped detection when the lymphatic system has been so thoroughly mapped throughout the body is surprising on its own, but the true significance of the discovery lies in the effects it could have on the study and treatment of neurological diseases ranging from autism to Alzheimer’s disease to multiple sclerosis.

“Instead of asking, ‘How do we study the immune response of the brain?’ ‘Why do multiple sclerosis patients have the immune attacks?’ now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels,” said Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA’s Center for Brain Immunology and Glia (BIG). “It changes entirely the way we perceive the neuro-immune interaction. We always perceived it before as something esoteric that can’t be studied. But now we can ask mechanistic questions.”

“We believe that for every neurological disease that has an immune component to it, these vessels may play a major role,” Kipnis said. “Hard to imagine that these vessels would not be involved in a [neurological] disease with an immune component.”

New Discovery in Human Body

Kevin Lee, PhD, chairman of the UVA Department of Neuroscience, described his reaction to the discovery by Kipnis’ lab: “The first time these guys showed me the basic result, I just said one sentence: ‘They’ll have to change the textbooks.’ There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation — and they’ve done many studies since then to bolster the finding — that it will fundamentally change the way people look at the central nervous system’s relationship with the immune system.”

Even Kipnis was skeptical initially. “I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped,” he said. “I thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not.”

‘Very Well Hidden’

The discovery was made possible by the work of Antoine Louveau, PhD, a postdoctoral fellow in Kipnis’ lab. The vessels were detected after Louveau developed a method to mount a mouse’s meninges — the membranes covering the brain — on a single slide so that they could be examined as a whole. “It was fairly easy, actually,” he said. “There was one trick: We fixed the meninges within the skullcap, so that the tissue is secured in its physiological condition, and then we dissected it. If we had done it the other way around, it wouldn’t have worked.”

After noticing vessel-like patterns in the distribution of immune cells on his slides, he tested for lymphatic vessels and there they were. The impossible existed. The soft-spoken Louveau recalled the moment: “I called Jony [Kipnis] to the microscope and I said, ‘I think we have something.'”

As to how the brain’s lymphatic vessels managed to escape notice all this time, Kipnis described them as “very well hidden” and noted that they follow a major blood vessel down into the sinuses, an area difficult to image. “It’s so close to the blood vessel, you just miss it,” he said. “If you don’t know what you’re after, you just miss it.”

“Live imaging of these vessels was crucial to demonstrate their function, and it would not be possible without collaboration with Tajie Harris,” Kipnis noted. Harris, a PhD, is an assistant professor of neuroscience and a member of the BIG center. Kipnis also saluted the “phenomenal” surgical skills of Igor Smirnov, a research associate in the Kipnis lab whose work was critical to the imaging success of the study.

Alzheimer’s, Autism, MS and Beyond

The unexpected presence of the lymphatic vessels raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it. For example, take Alzheimer’s disease. “In Alzheimer’s, there are accumulations of big protein chunks in the brain,” Kipnis said. “We think they may be accumulating in the brain because they’re not being efficiently removed by these vessels.” He noted that the vessels look different with age, so the role they play in aging is another avenue to explore. And there’s an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist.


Story Source:

The above post is reprinted from materials provided by University of Virginia Health System. Note: Materials may be edited for content and length.


Journal Reference:

  1. Antoine Louveau, Igor Smirnov, Timothy J. Keyes, Jacob D. Eccles, Sherin J. Rouhani, J. David Peske, Noel C. Derecki, David Castle, James W. Mandell, Kevin S. Lee, Tajie H. Harris, Jonathan Kipnis. Structural and functional features of central nervous system lymphatic vessels. Nature, 2015; DOI: 10.1038/nature14432

Cite This Page:

University of Virginia Health System. “Missing link found between brain, immune system; major disease implications.” ScienceDaily. ScienceDaily, 1 June 2015. <www.sciencedaily.com/releases/2015/06/150601122445.htm>.

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time.com: New research shows having good heart health is important for cognitive function

Having a healthy heart can help preserve brain processing and cognitive function over time, according to a new study published in the Journal of the American Heart Association.

Researchers looked at whether meeting certain markers of a healthy heart—including not smoking, maintaining a healthy body weight, being physically active, having a good diet and keeping blood pressure and cholesterol in check—had an impact on people’s cognitive abilities.

In the study, more than 1,000 men and women over age 40 had brain tests that assessed their memory and brain processing abilities, like how fast they could do a focus-intensive task. Six years later, the people were tested again. The researchers found that having more of the healthy heart factors was linked to better brain processing years later. It was also associated with less decline in functions like memory and executive functions like time management and focus.

“Achieving these ideal factors is really important not just for cardiovascular health but also for brain health,” says study author Hannah Gardener, an epidemiologist at University of Miami. “Some people may be more motivated by preserving their cognitive health. So I think it’s important to emphasize that striving to achieve ideal levels on these seven factors may also help preserve cognitive health later in life.”

But you don’t have to be perfect, Gardener says none of the people in the study achieved the targets for all six of the health factors, suggesting that even improvements in some areas, if not all, can benefit the brain. “People shouldn’t feel discouraged if one or two feels out of reach,” she says.

bird

Takut Stroke? Makan Pisang Setiap Hari!

Oleh: Dahlia Krisnamurti
Gaya Hidup – Rabu, 6 April 2011 | 22:09 WIB

big-dancing-banana-smiley-emoticonINILAH.COM, Jakarta – Pisang adalah buah yang banyak mengandung potasium yang berfungsi menstabilkan detak jantung, otak, dan proses fisiologi penting lainnya. Cukup makan pisang bisa ikut menurunkan risiko terkena stroke.

Stroke merupakan penyakit nomor tiga yang mematikan setelah jantung dan kanker. Karena itu, menjalani hidup sehat merupakan solusi jitu untuk mencegah penyakit berbahaya ini.

Peneliti dari Inggris dan Italia menyebutkan mengkonsumsi pisang tiga kali sehari layaknya minum obat akan memberikan kalium cukup untuk mengurangi kemungkinan menderita pembekuan darah di otak sekitar 21%.

Seseorang dianjurkan mengkonsumsi sekitar 2.300 mg potasium perhari. Sedangkan yang sering ditemukan, orang hanya mengkonsumsi kurang lebih 1.500 mg potasium per hari.

Pada pisang ditemukan kandungan potasium yang tinggi sebesar 400 mg yang setara dengan segelas orang juice atau kentang kukus.

Meskipun beberapa studi sebelumnya telah menyarankan pisang sebagai buah pencegah stroke, namun hal penting lainnya ialah mengendalikan tekanan darah, sebab hasilnya tidak selalu konsisten.

Dalam penelitian terbaru, yang diterbitkan dalam Journal of American College of Cardiology, para ilmuwan menganalisis data dari studi yang berbeda, kembali ke pertengahan tahun 1960an, dan digabungkan hasilnya untuk mendapatkan hasil keseluruhan.

Mereka menemukan orang hanya mengonsumsi kurang lebih 1.600 mg potasium per hari, kurang dari separuh jumlah kalium harian yang direkomendasikan untuk orang dewasa yaitu 3.500 mg.

Jika seseorang sudah cukup mengonsumsi kalium dengan jumlah tersebut, dijamin akan mendapat risiko stroke yang lebih rendah.

Pisang rata-rata mengandung sekitar 500 miligram kalium, yang membantu untuk menurunkan tekanan darah dan mengontrol keseimbangan cairan dalam tubuh. Terlalu sedikit kalium dapat mengakibatkan, lekas marah mual denyut jantung tidak teratur, dan diare.

Berkurangnya angka kematian

Sementara itu, peneliti dari Universitas Warwick dan Universitas Naples mengatakan asupan kalium di kebanyakan negara jauh di bawah jumlah harian yang disarankan.

Tetapi jika konsumen makan makanan kaya kalium lebih banyak dan juga mengurangi konsumsi garam mereka, angka kematian global per tahun dari stroke akan berkurang sebanyak satu juta.

Para peneliti mengatakan dalam laporannya, ini akan bermanfaat ke dalam pengurangan sebanyak 1.155.000 kematian stroke per tahun pada skala dunia.

Stroke, yang biasanya disebabkan ketika bentuk-bentuk bekuan dan blok suplai darah ke otak, membunuh sekitar 200 orang setiap hari di Inggris.

Banyak lagi yang tersisa dinonaktifkan dan dalam bahaya serangan kedua atau bahkan ketiga yang dapat membunuh mereka.

Mengobati dan merawat 100.000 orang yang terkena stroke setiap tahun di Inggris yang diperkirakan 2,3 miliar. Hanya kanker dan penyakit jantung membunuh lebih banyak orang.

“Penelitian ini menunjukkan makan banyak makanan kaya kalium, seperti pisang, date palm (buah pohon sejenis palem, Phoenix dactylifera) dan bayam, dapat mengurangi risiko Anda mengalami stroke,” ungkap seorang juru bicara Asosiasi Stroke.

“Tekanan darah tinggi adalah faktor risiko terbesar untuk penelitian stroke dan terakhir telah menunjukkan bahwa kalium dapat membantu menurunkan tekanan darah,” katanya. [mor]

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Eating three bananas a day slashes risk of a stroke
By Rajan | Wednesday, April 6th, 2011

The researchers say that eating three bananas a day slashes your risk of stroke. One banana in breakfast, one in lunch and one in the evening would give sufficient potassium to diminish the odds of suffering blood clots in the brain by up to twenty percent.

Even though some earlier studies have suggested that bananas could be significant for controlling blood pressure and preventing strokes. In the recent study carried out by researchers from the University of Warwick and the University of Naples analyzed the statistics of eleven diverse studies. They found that a daily potassium intake of around sixteen hundred milligram was sufficient to lower the risk of stroke.
The average banana contains about five hundred milligram of potassium that helps in lowering blood pressure and controls the balance of fluids in the body. The deficiency of potassium can escort to irregular heartbeat, irritability, nausea and diarrhea. The potassium intake in most countries is well below the suggested daily amount.
However, if people consume more potassium-rich foods and reduced their intake of salt then annual death rate due to strokes could be reduced by more than a million in a year. Strokes usually occurred when a clot forms and blocks the blood supply to the brain, reported the study published in the Journal of the American College of Cardiology.
According to a spokesman for the Stroke Association, this study suggests eating lots of potassium-rich foods like bananas, dates and spinach, could diminish your risk of having a stroke. High blood pressure is the single biggest risk aspect for stroke and past studies have shown that potassium could help to lower blood pressure.

Potassium
Overview:

Potassium is a very important mineral for the proper function of all cells, tissues, and organs in the human body. It is also an electrolyte, a substance that conducts electricity in the body, along with sodium, chloride, calcium, and magnesium. Potassium is crucial to heart function and plays a key role in skeletal and smooth muscle contraction, making it important for normal digestive and muscular function, too. Many foods contain potassium, including all meats, some types of fish (such as salmon, cod, and flounder), and many fruits, vegetables, and legumes. Dairy products are also good sources of potassium.

Having too much potassium in the blood is called hyperkalemia; having too little is known as hypokalemia. Keeping the right potassium balance in the body depends on the amount of sodium and magnesium in the blood. Too much sodium — common in Western diets that use a lot of salt — may increase the need for potassium. Diarrhea, vomiting, excessive sweating, malnutrition, malabsorption syndromes (such as Crohn’s disease) can also cause potassium deficiency, as well as use of a kind of heart medicine called loop diuretics.

Most people get all of the potassium they need from a healthy diet rich in vegetables and fruits. Older people have a greater risk of hyperkalemia because our kidneys are less efficient at eliminating potassium as we age. Older people should be careful when taking medication that may affect potassium levels, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and ACE inhibitors (see section on Interactions).

Whatever your age, talk to your doctor before taking potassium supplements.

Bone Health

At least one study shows a positive link between a diet rich in potassium and bone health. More research is needed to determine whether a diet high in potassium can reduce bone turnover in people.

Hypokalemia

The most important use of potassium is to treat the symptoms of hypokalemia (low potassium), which include weakness, lack of energy, muscle cramps, stomach disturbances, an irregular heartbeat, and an abnormal EKG (electrocardiogram, a test that measures heart function). Hypokalemia is usually caused by the body losing too much potassium in the urine or intestines; it’s rarely caused by a lack of potassium in the diet. Hypokalemia can be life-threatening and should always be treated by a doctor.

High Blood Pressure

Some studies have linked low levels of potassium in the diet with high blood pressure. And there is some evidence that potassium supplements might cause a slight drop in blood pressure. But not all studies agree — two large studies found no effect on blood pressure. It may be that taking potassium only helps lower blood pressure if you’re not getting enough of this mineral to start with. Before taking potassium or any supplement for high blood pressure, talk to your doctor.

Stroke

a lot of potassium in their diet have a lower risk of stroke. However, potassium supplements don’t seem to have the same benefit.

People who get a lot of potassium in their diet have a lower risk of stroke. However, potassium supplements don’t seem to have the same benefit.

Inflammatory Bowel Disease (IBD)

People with IBD (ulcerative colitis or Crohn’s disease) often have trouble absorbing nutrients from their intestine, and may have low levels of potassium and other important nutrients. If you have IBD, your doctor may check your potassium levels and recommend a supplement.

Dietary Sources:

Good sources of potassium include bananas, citrus juices (such as orange juice), avocados, cantaloupes, tomatoes, potatoes, lima beans, flounder, salmon, cod, chicken, and other meats.

Available Forms:

Several potassium supplements are on the market, including potassium acetate, potassium bicarbonate, potassium citrate, potassium chloride, and potassium gluconate. It is available in tablets, capsules, effervescent tablets, powders, and liquids.

Potassium can also be found in multivitamins.

How to Take It:

Potassium supplements, other than the small amount included in a multivitamin, should be taken only under your doctor’s supervision. Do not give potassium supplements to a child unless your doctor tells you to.

The recommended daily intakes of dietary potassium are listed below:

Pediatric

Infants birth – 6 months: 500 mg or 13 mEq
Infants 7 months – 12 months: 700 mg or 18 mEq
Children 1 year: 1,000 mg or 26 mEq
Children 2 – 5 years: 1,400 mg or 36 mEq
Children 6 – 9 years: 1,600 mg or 41 mEq
Children over 10 years: 2,000 mg or 51 mEq
Adult

2,000 mg or 51 Meq, including for pregnant and nursing women
Precautions:

Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.

Older adults should talk to their doctor before taking potassium supplements.

Side effects can include diarrhea, stomach irritation, and nausea. At higher doses, muscle weakness, slowed heart rate, and abnormal heart rhythm may occur. Contact your health care provider if you develop severe stomach pain, irregular heartbeat, chest pain, or other symptoms.

People with hyperkalemia or kidney disease should not take potassium supplements.

People who take ACE inhibitors, potassium-sparing diuretics, or the antibiotic trimethoprim and sulfamethoxazole (Bactrim, Septra) should not take potassium.

Possible Interactions:

If you are being treated with any of the following medications, you should not use potassium without first talking to your health care provider.

The following medications may cause potassium levels to rise:

Nonsteroidal anti-inflammatory drugs (NSAIDs): People who have poor kidney function and take NSAIDs are at higher risk.
ACE inhibitors: These drugs treat high blood pressure, heart disease, diabetes, some chronic kidney diseases, migraines, and scleroderma. People who take ACE inhibitors and also take NSAIDs, potassium-sparing diuretics, or salt substitutes may be particularly vulnerable to hyperkalemia (too much potassium). A rise in potassium from ACE inhibitors may also be more likely in people with poor kidney function and diabetes. ACE inhibitors include:
Benazepril (Lotensin)
Captopril (Capoten)
Enlapril (Vasotec)
Fosinopril (Monopril)
Lisinopril (Zestril)
Moexipril (Univasc)
Peridopril (Aceon)
Ramipril (Altace)
Trandolapril (Mavik)
Heparin (used for blood clots)
Cyclosporine (used to suppress the immune system)
Trimethoprimand sulfamethoxazole, called Bactrim or Septra (an antibiotic)
Beta-blockers: Used to treat high blood pressure, glaucoma, migraines
Atenolol (Tenormin)
Metoprolol (Lopressor, Toprol-XL)
Propranolol (Inderal)
The following medications may cause potassium levels to decrease:

Thiazide diuretics
Hydrochlorothiazide
Chlorothiazide (Diuril)
Indapamide (Lozol)
Metolzaone (Zaroxolyn)
Loop diuretics
Furosemide (Lasix)
Bumetanide (Bumex)
Torsemide (Demadex)
Ethacrynic acid (Edecrin)
Corticosteroids
Amphotericin B (Fungizone)
Antacids
Insulin
Fluconazole (Diflucan): Used to treat fungal infections
Theophylline (TheoDur): Used for asthma
Laxatives
If you are taking any of these medications, it is important for your doctor to test your potassium levels to see whether or not you need a supplement. Do not start taking a supplement on your own.

Other potential interactions include:

Digoxin — Low blood levels of potassium increase the likelihood of toxic effects from digoxin, a medication used to treat abnormal heart rhythms and heart failure. Your doctor will test your potassium levels to make sure they stay normal.

Reviewed last on: 5/6/2009
Steven D. Ehrlich, NMD, Solutions Acupuncture, a private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.
Supporting Research

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Appel LJ. Nonpharmacologic therapies that reduce blood pressure: a fresh perspective. Clin Cardiol. 1999;22(Suppl. III):III1-III5.

Apstein C. Glucose-Insulin-Potassium for acute myocardial infraction: remarkable results from a new prospective, randomized trial. Circ. 1998;98:2223-2226.

Apstein CS, Opie Lh. Glucose-insulin-potassium (GIK) for acute myocardial infarction: a negative study with a positive value. Cardiovasc Drugs Ther. 1999;13(3):185-189.

Ascherio A, Rimm EB, Hernan MA, et al. Intake of potassium, magnesium, calcium, and fiber and risk of stroke among U.S. men. Circ. 1998;98:1198-1204.

Brancati FL, Appel LJ, Seidler AJ, Whelton PK. Effect of potassium supplementation on blood pressure in African Americans on a low-potassium diet. Arch Intern Med. 1996;156:61-72.

Brater DC. Effects of nonsteroidal anti-inflammatory drugs on renal function: focus on cyclooxygenase-2-selective inhibition. Am J Med. 1999;107(6A):65S-70S.

Burgess E, Lewanczuk R, Bolli P, et al. Lifestyle modifications to prevent and control hypertension. 6. Recommendations on potassium, magnesium and calcium. Canadian Hypertension Society, Canadian Coalition for High Blood Pressure Prevention and Control, Laboratory Centre for Disease Control at Health Canada, Heart and Stroke Foundation of Canada. CMAJ. 1999;160(9 Suppl):S35-S45.

Cappuccio EP, MacGregor GA. Does potassium supplementation lower blood pressure? A meta-analysis of published trials. J Hypertens. 1991;9:465-473.

Chiu TF, Bullard MJ, Chen JC, Liaw SJ, Ng CJ. Rapid life-threatening hyperkalemia after addition of amiloride HCL/hydrochlorothiazide to angiotensin-converting enzyme inhibitor therapy. Ann Emerg Med. 1997;30(5):612-615.

Dickinson HO, Nicolson DJ, Campbell F, Beyer FR, Mason J. Potassium supplementation for the management of primary hypertension in adults. Cochrane Database Syst Rev. 2006 Jul 19;3:CD004641. Review.

Hermansen K. Diet, blood pressure and hypertension. Br J Nutr. 2000:83(Suppl 1):S113-119.

Heyka R. Lifestyle management and prevention of hypertension. In: Rippe J, ed. Lifestyle Medicine. 1st ed. Malden, Mass: Blackwell Science; 1999:109-119.

Houston MC. Treatment of hypertension with nutraceuticals, vitamins, antioxidants and minerals. Expert Rev Cardiovasc Ther. 2007 Jul;5(4):681-91.

Howes LG. Which drugs affect potassium? Drug Saf. 1995;12(4):240-244.

Iso H, Stampfer MJ, Manson JE, et al. Prospective study of calcium, potassium, and magnesium intake and risk of stroke in women. Stroke. 1999;30(9):1772-1779.

Joint National Committee. Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch Int Med. 1997;157:2413-2446.

Kendler BS. Recent nutritional approaches to the prevention and therapy of cardiovascular disease. Prog Cardiovasc Nurs. 1997;12(3):3-23.

Krauss RM, Eckel RH, Howard B, et al. AHA dietary guidelines. Revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation. 2000;102:2284-2299.

Lanham-New SA. The balance of bone health: tipping the scales in favor of potassium-rich, bicarbonate-rich foods. J Nutr. 2008;138(1):172S-177S.

Matsui H, Shimosawa T, Uetake Y, Wang H, Ogura S, Kaneko T, et al. Protective effect of potassium against the hypertensive cardiac dysfunction: association with reactive oxygen species reduction. Hypertension. 2006 Aug;48(2):225-31.

Myers VH, Champagne CM. Nutritional effects on blood pressure. Curr Opin Lipidol. 2007 Feb;18(1):20-4.

Matsumura M, Nakashima A, Tofuku Y. Electrolyte disorders following massive insulin overdose in a patient with type 2 diabetes. Intern Med. 2000;39(1):55-57.

Newnham DM. Asthma medications and their potential adverse effects in the elderly: recommendations for prescribing. Drug Saf. 2001;24(14):1065-1080.

O’Shaughnessy KM. Role of diet in hypertension management. Curr Hypertens Rep. 2006 Aug;8(4):292-7. Review.

Perazella MA. Trimethoprim-induced hyperkalemia: clinical data, mechanism, prevention and management. Drug Saf. 2000;22(3):227-236.

Perazella M, Mahnensmith R. Hyperkalemia in the elderly. J Gen Intern Med. 1997;12:646-656.

Physicians’ Desk Reference. 55th ed. Montvale, NJ: Medical Economics Co., Inc.; 2001:1418-1422, 2199-2207.

Pikilidou MI, Lasaridis AN, Sarafidis PA, Tziolas IM, Zebekakis PE, Dombros NV, Giannoulis E. Blood pressure and serum potassium levels in hypertensive patients receiving or not receiving antihypertensive treatment. Clin Exp Hypertens. 2007;29(8):563-73.

Poirier TI. Reversible renal failure associated with ibuprofen: case report and review of the literature. Drug Intel Clin Pharm. 1984;18(1):27-32.

Preston RA, Hirsh MJ MD, Oster, JR MD, et al. University of Miami Division of Clinical Pharmacology therapeutic rounds: drug-induced hyperkalemia. Am J Ther. 1998; 5(2):125-132.

Rafferty K, Heaney RP. Nutrient effects on the calcium economy: emphasizing the potassium controversy. J Nutr. 2008;138(1):166S-171S.

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Ray K, Dorman S, Watson R. Severe hyperkalemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction. J Hum Hypertens. 1999;13(10):717-720.

Reif S, Klein I, Lubin F, Farbstein M, Hallak A, Gilat T. Pre-illness dietary factors in inflammatory bowel disease. Gut. 1997;40:754-760.

Sacks FM, Willett WC, Smith A, et al. Effect on blood pressure of potassium, calcium, and magnesium in women with low habitual intake. Hypertens. 1998;31(1):131-138.

Shionoiri H. Pharmacokinetic drug interactions with ACE inhibitors. Clin Pharmacokinet. 1993;25(1):20-58.

Singh RB, Singh NK, Niaz MA, Sharma JP. Effect of treatment with magnesium and potassium on mortality and reinfarction rate of patients with suspected acute myocardial infarction. Int J Clin Pharmacol Thera. 1996;34:219-225.

Stanbury RM, Graham EM. Systemic corticosteroid therapy — side effects and their management. Br J Ophthalmol. 1998;82(6):704-708.

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Suter PM. Potassium and Hypertension. Nutrition Reviews. 1998;56:151-133.

Whang R, Oei TO, Watanabe A. Frequency of hypomagnesia in hospitalized patients receiving digitalis. Arch Intern Med. 1985;145(4):655-656.

Whelton, A, Stout RL, Spilman PS, Klassen DK. Renal effects of ibuprofen, piroxicam, and sulindac in patients with asymptomatic renal failure. A prospective, randomized, crossover comparison. Ann Intern Med. 1990;112(8):568-576.

Wu G, Tian H, Han K, Xi Y, Yao Y, Ma A. Potassium magnesium supplementation for four weeks improves small distal artery compliance and reduces blood pressure in patients with essential hypertension. Clin Exp Hypertens. 2006 Jul;28(5):489-97.

Young DB, Lin H, McCabe RD. Potassium’s cardiovascular protective mechanisms. Am J Physiology. 1995;268(part 2):R825-R837.

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Februari 3, 2017

jatuHAT1: hipoglisin, ati2

Filed under: GLOBAL ECONOMY,Medicine — bumi2009fans @ 1:47 am

TEMPO.CO, New Delhi—Setiap tahun selama lebih dari dua dekade terakhir, 100 anak tewas di bagian utara India.

Misteri ini membuat otoritas kesehatan India dan para orang tua resah, karena penyebabnya belum juga ditemukan.

Baca: Serunya Perang Twitter J.K Rowling vs Pendukung Donald Trump

Sebelum tewas, anak-anak di Negara Bagian Bihar ini tiba-tiba mengalami kejang-kejang dan kehilangan kesadaran.

 

Namun penyebab kematian tragis itu akhirnya terkuak awal bulan ini.

Seperti dilansir BBC, Jumat 3 Februari 2017, peneliti Amerika Serikat dan India sepakat bahwa kematian para bocah itu disebabkan karena mereka memakan buah leci saat perut masih kosong.

Penelitian terbaru yang dimuat dalam jurnal kesehatan bergengsi, The Lancet, menegaskan temuan yang menyatakan para korban keracunan leci.

Sebagian besar korban, kata The Lancet, merupakan anak-anak dari keluarga miskin yang memakan buah leci yang jatuh di tanah. Bihar merupakan daerah penghasil leci di India.

“Leci memiliki racun bernama hipoglisin, yang menahan tubuh dari memproduksi glukosa. Hal ini sangat berdampak buruk bagi para korban yang tingkat gula darahnya sudah sangat rendah karena tidak makan malam,” demikian tulis The Lancet.

Anak-anak ini akan menjerit di malam hari sebelum mengalami kejang-kejang dan tidak sadarkan diri, karena mengalami pembengkakan otak secara tiba-tiba.

Temuan ini diperoleh setelah para peneliti memeriksa anak-anak yang selamat di rumah sakit Muzaffarpur antara Mei-Juli 2014. Kondisi para korban ternyata sama dengan insiden yang terjadi sebelumnya di Karibia.

Wabah di Karibia dipicu oleh buah lokal bernama ackee. Buah ini mengandung racun hipoglisin, persis seperti yang ditemukan di dalam buah leci.

Hasil penelitian ini menjadi dasar pengumuman Kementerian Kesehatan yang meminta para orang tua memastikan anak mereka makan terlebih dulu dan membatasi buah leci yang dikonsumsi.

Anak-anak yang terkena sindrom ini harus ditangani sebagai pasien hipoglikemia atau tekanan gula darah rendah.

Sejak kasus ini berhasil dipecahkan, jumlah anak yang meninggal di Karibia turun drastis.

BBC | THE NEW YORK TIMES | SITA PLANASARI AQUADINI

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e-medicine: Background

Ackee, the national fruit of Jamaica, is a food staple in many Jamaican diets. The fruit is rich in essential fatty acids, vitamin A, zinc, and protein. [1, 2] Consumption of unripe ackee fruit, however, can lead to potentially fatal toxicity, known as Jamaican vomiting sickness.

The word “ackee” originated from the Twi language. The ackee tree is a tropical evergreen tree that can grow as tall as 40 feet. Its leaves are broad and pinnate; its approximately 10-cm wide, 100-g fruit may be colored anywhere from straw to bright red. The fruit splits open while still on the tree to reveal three glassy black seeds surrounded by a thick, oily, yellow aril. (See the images below.)The fruit should be allowed to open and ripen naturally on the tree.

The ackee tree is indigenous to West Africa, where it is called ankye or ishin. Thomas Clarke, Jamaica’s first botanist, introduced the plant to the island in 1778. However, the ackee tree, Blighia sapida, was named after the infamous Captain William Bligh who took the breadfruit tree to the West Indies. The tree also grows in other West Indian Islands such as Cuba, Haiti and Barbados, in Central America, and in Southern Florida. [3]

An association between ackee poisoning and Jamaican vomiting sickness was first noted in 1875 and documented in 1904. In 1937, Jordan and Burrows found a water-soluble toxic material in the seed and pods of the ackee fruit. In 1954, Hassal et al were the first to isolate two toxic compounds in their crystalline form. These compounds were called hypoglycin A and hypoglycin B because of their hypoglycemic activity.

Two toxic water-soluble substances can be extracted from the fruit. The first toxin, hypoglycin A, is L-α -amino-β -[methylene cyclopropyl]propionic acid. Hypoglycin B is a γ -L-glutamyl derivative of hypoglycin A and is less toxic than hypoglycin A. Hypoglycin A, but not hypoglycin B, can be found in the aril of the fruit. The unripe fruit has a much higher concentration of hypoglycin A (approximately 20 times) than that of the ripe aril. Both components are found in the seeds. Therefore, the seeds and the membrane at the base of the seed mantle are always poisonous.

Hypoglycin A, which is now simply called hypoglycin, is metabolized by means of transamination and oxidative decarboxylation to methylene cyclopropyl acetic acid (MCPA). MCPA forms nonmetabolizable carnitine and coenzyme A (CoA) esters, thereby depressing tissue levels of these cofactors and making them less available for other biochemical reactions. Hypoglycemia results because both CoA and carnitine are necessary cofactors for long-chain fatty acid oxidation and because oxidation is a requisite for active gluconeogenesis. MCPA also inhibits the dehydrogenation of several acyl-CoA dehydrogenases, including butyryl CoA, glutaryl CoA, and isovaleryl CoA. As a result of the inhibition of butyryl CoA dehydrogenase, the oxidation of long-chain fatty acids stops at the level of hexanoyl CoA and butyryl CoA. This effect leads to the decreased production of nicotinamide adenine dinucleotide (NADH) and acetyl CoA.

Because NADH and acetyl CoA are required as a cofactor of 3-phosphoglyceraldehyde phosphate dehydrogenase and as an activator of pyruvate carboxylase, respectively, their diminished concentration contributes to the inhibition of gluconeogenesis. The inhibition of glutaryl CoA dehydrogenase results in the accumulation of glutaryl CoA, which could inhibit transmitochondrial malate transport, a rate-limiting step in the early phase of gluconeogenesis, and consequently suppress gluconeogenesis. Altered levels of circulating insulin do not cause hypoglycemia associated with hypoglycin action.

Frequency

United States

Ackee is illegal in the United States; therefore, underreporting may occur. To date, 2 cases of ackee poisoning have been reported in the United States. The first was in Ohio in a Jamaican woman who presented with Jamaican vomiting sickness after a meal of ackee fruit. The second was in Connecticut in a young Jamaican man who presented with cholestatic jaundice secondary to the chronic ingestion of ackee fruit.

International

The epidemiology of ackee poisoning has not been well characterized, and the true incidence and mortality rate are believed to be underreported. At the request of the Jamaican Ministry of Health (JMH), the Centers for Disease Control and Prevention (CDC) identified 38 cases of Jamaican vomiting sickness and 6 deaths from 1989-1991. This problem is endemic in Jamaica; 271 cases have been reported to the JMH since 1980.

In 1998, an unexplained outbreak of epidemic fatal encephalopathy (EFE) occurred in Burkina Faso in West Africa. The only factor associated with EFE was the presence of ackee trees within 100 m of the households. The consumption of unripe ackee fruit possibly caused this epidemic.

In late 2000, the CDC provided technical support to the Ministry of Health in Haiti during an outbreak of ackee poisoning in the northern region of that country. [4, 5]More than 100 cases of acute illness and death were reported.

From 1998-2001, reports detailed 16 deaths of children in Surinam along the River Maroni, which separates Surinam and French Guyana. The deaths were subsequently linked to ackee fruit poisoning as result of the misuse of the plant by Maroon witch doctors to “cure” some pathologies especially acute forms of diarrhea in children. [6]

Mortality/Morbidity

Before treatments were developed, the mortality rate was as high as 80%. No deaths from ackee fruit poisoning have been reported in the United States. In Jamaica, 6 deaths were reported in 1989-1991. A link between ackee fruit poisoning and unexplained deaths of preschool children in West Africa has been postulated.

Race

Ackee is consumed mostly in West Africa and Jamaica; therefore, most cases have occurred in blacks.

Sex

No difference in the sex distribution is noted.

Age

In Jamaica, the annual rate of ackee poisoning is 2 cases per 100,000 persons younger than 15 years and 0.4 case per 100,000 persons older than 15 years.

THE ACKEE FRUIT (BLIGHIA SAPIDA) AND ITS ASSOCIATED TOXIC EFFECTS

Introduction
The islands of the Caribbean account for less than 0.03% of the world’s landmass and are enriched with a wide variety of flora and fauna. More than 2% of the world’s total number of plant and vertebrate species are endemic there [1]. Due to the regions rich diversity of flora and fauna, there is increasing interest in the isolation of natural products which have been found to possess a wide range of interesting biological activities. Hypoglycin A, an unusual amino acid, was initially isolated from the ackee fruit and has been the focus of many years of research due to its ability to significantly reduce blood glucose levels and induce hypoglycemia.

The Ackee Fruit
The ackee is a tropical fruit belonging to the Sapindaceae family. It has its origin in West Africa but has traversed the Atlantic Ocean making the Caribbean its home. Its exact date of arrival is unknown but it is believed that the fruit was transported to the Caribbean by slave ships sometime around the 18th century. The trivial name ackee, is derived from the terms “anke” and “akye-fufuo” which are used to describe the fruit in West Africa. The fruit was named Blighia sapida in honor of the infamous Captain William Bligh of Mutiny on the Bounty who transported the fruit from Jamaica to England in 1793 [2].

Consumption of the ackee is mainly in Jamaica, Haiti and some parts of West Africa. In Jamaica, the fruit serves as a major component of the national dish ackee and codfish. There, the fruit is also processed in brine, canned and exported earning over US $13 million annually. The fruit is divided into three major sections, the pod, the seed and the edible portion, the arilli. (Figure 1)

 

The fruit while beautiful in appearance is not as harmless as it seems. Its intense red color may well allude to the dangers involved in consuming the immature fruit. The ackee has been the cause of widespread epidemics both in Jamaica and in West Africa. From as early as the 19th century there were speculations that the fruit may be toxic. It was not until 1955, however, that the actual causative factor of its toxicity was elucidated.

Jamaican Vomiting Sickness
Between the years 1880 – 1955, there evolved an illness that was found predominantly in Jamaica [3]. The illness was accompanied by severe bouts of vomiting and was named Jamaican Vomiting Sickness (JVS). JVS is also referred to as Toxic Hypoglycemic Syndrome and is associated with severe disturbances in carbohydrate and lipid metabolism. Clinical features of the illness include vomiting, abdominal pain, depletion of hepatic glycogen, hypoglycemia, aciduria, coma and in severe cases death [4].

In 1955 the causative factor of JVS was isolated, a non proteinogenic amino acid, hypoglycin A, so named due to its ability to induce severe hypoglycemia [5]. Its chemical structure was elucidated in 1958 and scientifically it is referred to as L-alpha-amino-beta-methylene cyclopropane propionic acid [6]. (Figure 2)

 

Figure 2.There were several difficulties encountered by researchers in identifying the causative factor of JVS. The ackee is eaten by many without ill effects. It was therefore not thought to be the likely source of the illness. Hypoglycin A is found predominantly in the immature fruit. Concentrations within the arilli ranges from over 1000 ppm in the immature fruit to less than 0.1 ppm in the fully mature fruit [7]. Ill effects occur only when the immature fruit is consumed.

Metabolism of Hypoglycin A
Thorough investigation of the toxicity associated with hypoglycin A revealed that the actual causative agent of JVS is a metabolite of hypoglycin A called methylenecyclopropane acetyl CoA (MCPA-CoA). Hypoglycin A is transaminated to methylenecyclopropyl-alanine (MCPA) and subsequently undergoes oxidative decarboxylation to form MCPA-CoA [8]. MCPA-CoA exerts its effect by inhibiting several coenzyme A dehydrogenases which are essential for gluconeogenesis [9]. Depletion of glucose reserves and the inability of cells to regenerate glucose leads to hypoglycemia.

 

Figure 3. Metabolism of Hypoglycin A [8]Fruit Maturity
The ackee takes seven to eight weeks to attain full maturity. During weeks two through three of fruit development, the fruit doubles in size after which the fruit increases at a much slower rate [10]. At full maturity the fruits are pear shaped and acquire a red or a yellow tinge with red coloration. The pods then open revealing the seeds and 3 fleshy arilli. (Figure 4) Fruits are safe for consumption only at this stage of maturity.

 

It has been hypothesized that during fruit maturity hypoglycin A is translocated from the arilli to the seeds of the fruit. There it is converted to the dipeptide hypoglycin B. (Figure 5) As the fruit matures, the concentration of hypoglycin B increases from 0.4 mg/g to 3.3 mg/g [11]. Hypoglycin B is only found in the seeds of the fruit. It also possesses hypoglycemic activity but is less potent than hypoglycin A.

Recent Reports of Ackee Intoxication
In recent years, there have been reported incidences of toxic hypoglycemic syndrome in Burkina Faso, The Ivory Coast, Togo and Benin. Lethality was 100% in the Burkina Faso epidemic and victims of the illness were all children [12]. Deaths were linked to ackee intoxication due to enhanced concentrations of dicarboxylic acids in the urine of the victims. Suggestions have been made that the ingestion of unripe ackee fruits may be responsible for a substantial number of unexplained deaths in preschool children in West Africa [13]. Children are the most susceptible to the illness and there appears to be ignorance with regards to the toxic nature of the immature fruit. Ongoing educational campaigns are of utmost importance for the total eradication of this deadly syndrome.

Treatment of Hypoglycin A Toxicity
There is no standard method of treating toxic hypoglycemic syndrome. Care has been focused on relieving symptoms and providing supportive care. Early sugar and glucose administration is also recommended. Other treatments to relieve symptoms of the ailment include the use of antiemetics to control vomiting, gastrointestinal decontaminants, dextrose and glucose stimulators and benzodiazepines to control seizures [14]. The administration of riboflavin and glycine have also been reported to antagonize the effects of hypoglycin A intoxication [15]. It is believed that riboflavin stimulates the de novo synthesis of acyl-CoA dehydrogenases while glycine conjugates with excess dicarboxylic acids produced due to impaired lipid metabolism [16].

Analysis and Quantification of Hypoglycin A
In earlier years, the analysis and quantification of hypoglycin A was difficult and time consuming due to co-elution problems with the amino acids leucine, isoleucine and valine. Ion exchange amino acid analysis was limited by the fact that amino acids with similar solubility and chromatographic properties to hypoglycin A caused problems in resolution. Different analytical techniques have been utilized to solve this problem and include fluorimetry, spectrophotometry and high performance liquid chromatography (HPLC). HPLC is currently the method of choice for hypoglycin A quantification. It presents a rapid, reliable and reproducible means of quantifying the amino acid. Hypoglycin A is first derivatized and subsequently analyzed on a reversed-phase liquid chromatography system. Two derivatizing agents are currently being used, O-phthalaldehyde (OPA) and phenylisothiocyanate (PITC). This method of quantifying hypoglycin A was initially developed in 1989 through collaborative efforts between the Jamaica Bureau of Standard and the University of Florida [17]. The Pico-Tag method which utilizes phenylisothiocyanate as the derivatizing agent was developed by a research group in Canada [18]. Currently, low nanogram quantities of the analyte may be detected.

Other Metabolites in the Ackee Fruit
A number of other metabolites have been isolated from the ackee fruit. While not as biologically interesting, the compounds are unusual in their structure. Blighinone, a sparingly soluble quinone was isolated from the arilli of the fruit [19]. Vomifoliol, has been isolated from the leaves and stems of the plant and has been implicated in the endogenous regulation of stomatal aperture [20]. (Figure 6)


Figure 6More recently, another non-proteinogenic amino acid (2S, 1’S, 2’S)-2-(2’-carboxycyclopropyl)glycine (CCG 1), was isolated from the fruit [21]. It is similar in structure to hypoglycin A with respect to the presence of a cycopropane ring structure which is a rare occurrence in nature (Figure 7).


Figure 7Conclusion:
The plants found in the Caribbean continue to be a rich store house of interesting biological molecules. The ackee serves as one such example and has played an intriguing role in the history of the Caribbean. It has sparked the interest of a number of researchers in Jamaica and internationally. Research on this unusual fruit continues as well as other plants in the region with the hope of finding other biologically active components which may be of therapeutic value in the treatment of various diseases.

References

1. Yarnell, A. Chemical and Engineering News, 2004, 82, 33.

2. Lewis, C. B. Information Bulletin of the Scientific Research Council 1965, 1, 12-14.

3. Feng, P. C. West Indian Med. J. 1969, 18, 238-243.

4. Tanaka, K. and Ikeda, Y., Prog. Clin. Biol. Res. 1990, 321,167-184.

5. Hassall, C. H. and Reyle K. West Indian Med. J. 1955, 4, 83-90.

6. Carbon, J. A., Martin, W. B. and Swett, L. R. J. Am. Chem. Soc. 1958, 80, 1002.

7. Brown, M., Bates, R. P., McGowan, C. and Cornel, J. A. J. Food Saf. 1992, 12, 167-177.

8. Von Holt, C. Biochim. Biophys. Acta 1966, 125, 1-10.

9. Von Holt, C., Von Holt, M. and Bohm, H. Biochim Biophys Acta 1966, 125, 11-21.

10. Stair, M. A. and Sidrak, G. Jagrist 1992, 4, 10-13.

11. Kean, E. A. and Hare E. R. Phytochemistry 1980, 19, 199-203.

12. Barennes, H., Valea, I., Boudat, A. M., Idle, J. R. and Nagot, N. Food and Chemical Toxicology 2004, 42, 809-825.

13. Meda, H. A., Diallo, B., Buchet, J. P., Lison, D., Barennes, H., Ouangre, A., Sanou, M., Cousens, S., Tall, F. and Perre, P.van-de The Lancet 1999, 353, 536- 540.

14. eMedicine, Holson, D. Toxicity, Plants – Ackee Fruit.

15. Duff, D.A., Price, S.C. and Snell, K. Biochem. Soc. Trans.1980, 8, 574-575.

16. Al-Bassam, S.S and Sherratt, H.S.A. (1981) Biochem. Pharmac.1981, 30, 2817-2824.

17. McGowan, C., Wiley, V. A. and Bates, R. P. Biochromatography 1989, 4(3), 161-164.

18. Ghulam, S. and Botting, H. G. J. Assoc.Off. Anal. Chem.1994, 77, 1175-1179.

19. Garg, H. S. and Mitra, C. R. Tetrahedron Lett. 1968, 13, 1549-1552.

20. Stuart, K. L., Roberts, E. V. and Whittle, Y. G. Phytochemistry 1976, 15, 332-333.

21. Natalini, B., Capodiferro, V., De Luca, C. and Espinal, R. J Chromatogr. A 2000, 873, 283-286.

November 7, 2016

I heart you: kopi @otot saluran indung … 290511_081116

Filed under: Medicine — bumi2009fans @ 3:02 pm

 

Eur J Clin Nutr. 2012 Aug;66(8):872-7. doi: 10.1038/ejcn.2012.68. Epub 2012 Jun 20.

The effect of coffee consumption on serum lipids: a meta-analysis of randomized controlled trials.

Abstract

BACKGROUND/OBJECTIVES:

Numbers of epidemiological studies assessing coffee consumption and serum lipids have yielded inconsistent results. We aimed to evaluate the effects of coffee intake on serum lipids.

SUBJECTS/METHODS:

We searched several English and Chinese electronic databases up to September 2011 for randomized controlled trials of coffee on serum lipids. Weighted mean effect size was calculated for net changes in serum lipids by using random-effect models or fixed-effect models. Subgroup and meta-regression analyses were conducted to explore possible explanations for heterogeneity among trials.

RESULTS:

Twelve studies conducted in Western countries with a total of 1017 subjects were identified. Meta-analyses showed, on average, drinking coffee for 45 days was associated with an increase of 8.1 mg/dl (95% confidence interval (CI): 4.5, 11.6; P<0.001) for total cholesterol (TC), 5.4 mg/dl (95% CI: 1.4, 9.5; P=0.009) for low-density lipoprotein cholesterol (LDL-C) and 12.6 mg/dl (95% CI: 3.5, 12.6; P=0.007) for triglyceride (TG). The increase in TC were greater in trials using unfiltered coffee and caffeinated coffee as the treatment group. Those who had hyperlipidemia were more sensitive to the cholesterol-raising effect of coffee. Meta-regression analysis revealed a positive dose-response relation between coffee intake and TC, LDL-C and TG.

CONCLUSION:

The intake of coffee especially unfiltered coffee is contributed significantly to the increase in TC, LDL-C and TG, and the changes were related to the level of intake. Studies of coffee intake on serum lipids in Asian populations should be performed.

PMID:
22713771
DOI:
10.1038/ejcn.2012.68
[PubMed – indexed for MEDLINE]

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Am J Clin Nutr. 2011 Aug;94(2):601-10. doi: 10.3945/ajcn.110.010926. Epub 2011 Jun 29.

Green tea intake lowers fasting serum total and LDL cholesterol in adults: a meta-analysis of 14 randomized controlled trials.

Abstract

BACKGROUND:

The effect of green tea beverage and green tea extract on lipid changes is controversial.

OBJECTIVE:

We aimed to identify and quantify the effect of green tea and its extract on total cholesterol (TC), LDL cholesterol, and HDL cholesterol.

DESIGN:

We performed a comprehensive literature search to identify relevant trials of green tea beverages and extracts on lipid profiles in adults. Weighted mean differences were calculated for net changes in lipid concentrations by using fixed-effects or random-effects models. Study quality was assessed by using the Jadad score, and a meta-analysis was conducted.

RESULTS:

Fourteen eligible randomized controlled trials with 1136 subjects were enrolled in our current meta-analysis. Green tea consumption significantly lowered the TC concentration by 7.20 mg/dL (95% CI: -8.19, -6.21 mg/dL; P < 0.001) and significantly lowered the LDL-cholesterol concentration by 2.19 mg/dL (95% CI: -3.16, -1.21 mg/dL; P < 0.001). The mean change in blood HDL-cholesterol concentration was not significant. Subgroup and sensitivity analyses showed that these changes were not influenced by the type of intervention, treatment dose of green tea catechins, study duration, individual health status, or quality of the study. Overall, no significant heterogeneity was detected for TC, LDL cholesterol, and HDL cholesterol; and results were reported on the basis of fixed-effects models.

CONCLUSION:

The analysis of eligible studies showed that the administration of green tea beverages or extracts resulted in significant reductions in serum TC and LDL-cholesterol concentrations, but no effect on HDL cholesterol was observed.

PMID:
21715508
DOI:
10.3945/ajcn.110.010926

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Awas, Kopi Bikin Wanita Sulit Hamil!
Tribune News – Sab, 28 Mei 2011

… mau tau lebe banyak soal kopi : KOPI atawa TEH, sami mawon dan soal keracunan kopi: caffein intoxication

TRIBUNNEWS.COM – Minum kopi membuat wanita lebih sulit hamil, sebuah penelitian menyebutkannya.

Ini diperkirakan karena Kafein, yang terkandung dalam kopi merusak transportasi telur dari ovarium ke rahim, sebut para ilmuwan dari Amerika.

Penelitian yang melibatkan 9.000 wanita ini menemukan bahwa minum lebih dari empat cangkir kopi sehari memotong kemungkinan hamil hingga seperempat kali.

Penyelidikan terbaru yang dilakukan pada mencit menunjukkan bahwa kafein menghambat kontraksi saluran tuba yang dibutuhkan untuk membawa telur ke rahim.

Kafein mengaktifkan sel-sel alat pacu jantung khusus di dinding tabung. Sel-sel gelombang koordinasi kontraksi tabung yang bergerak membawa telur menuju rahim.

Pemimpin studi Sean Ward, dari University of Nevada di Reno, AS, mengatakan temuan ini memberikan penjelasan menarik tentang mengapa wanita dengan konsumsi kafein tinggi seringkali memakan waktu lebih lama untuk hamil daripada wanita yang tidak mengonsumsi kafein. (*)

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Female coffee drinkers at risk of reduced fertility
Posted Thu, 26 May 2011 11:11:01 GMT by Kieran Ball
Female coffee drinkers at risk of reduced fertility

A new study shows that women should consider giving up coffee to maximise their chances of getting pregnant. The report, in the British Journal of Pharmacology, focuses on research from the University of Nevada School of Medicine indicating that caffeine inhibits the movement of eggs along the fallopian tubes, reducing the chance of conception.

By studying mice, Professor Sean Ward’s team found that caffeine inhibited the actions of specialised cells along the walls of the fallopian tubes that help carry the eggs from the ovaries to the uterus. The researcher found that caffeine affected the action of ‘pacemaker’ cells, slowing the transit of eggs.

Professor Ward believes that this may explain why women who drink caffeinated drinks, such as coffee and cola, may have trouble becoming pregnant:

”This provides an intriguing explanation as to why people with high caffeine consumption can often take longer to conceive than women who do not consume caffeine.”

The professor went on to say that caffeine’ effect on muscle activity within the fallopian tubes occurs ”in concentrations well within what people are drinking”.

Professor Ward’s work is the latest in a number of studies that has linked caffeine to reduced fertility. A few years ago, Ronald Gray, a professor at John Hopkins Bloomberg School of Public Health researched the connection between caffeine and fertility and showed that women who consumed more than 300mg of caffeine each day (the equivalent of two average cups of coffee) decreased their chance of becoming pregnant by about 27% compared to those who did not drink caffeinated drinks.

Ward suggests that the research could further our understanding of the mechanisms at work within the fallopian tubes and help research into ectopic pregnancies – a painful condition where embryos become implanted in the fallopian tubes:

”As well as potentially helping women who are finding it difficult to get pregnant, a better understanding of the way fallopian tubes work will help doctors treat pelvic inflammation and sexually transmitted disease more successfully.”

Caffeine is thought to be the most frequently ingested pharmacologically active substance in the world today.

Why Caffeine Can Reduce Fertility in Women

ScienceDaily (May 23, 2011) — Caffeine reduces muscle activity in the fallopian tubes that carry eggs from the ovaries to the womb, according to recent animal studies.

“Our experiments were conducted in mice, but this finding goes a long way towards explaining why drinking caffeinated drinks can reduce a woman’s chance of becoming pregnant,” says Professor Sean Ward from the University of Nevada School of Medicine, Reno. Ward’s study is published in the British Journal of Pharmacology.

Human eggs are microscopically small, but need to travel to a woman’s womb if she is going to have a successful pregnancy. Although the process is essential for a successful pregnancy, scientists know little about how eggs move through the muscular Fallopian tubes. It was generally assumed that tiny hair-like projections, called cilia, in the lining of the tubes, waft eggs along assisted by muscle contractions in the tube walls.

By studying tubes from mice, Professor Ward and his team discovered that caffeine stops the actions of specialised pacemaker cells in the wall of the tubes. These cells coordinate tube contractions so that when they are inhibited, eggs can’t move down the tubes. In fact these muscle contractions play a bigger role than the beating cilia in moving the egg towards the womb. “This provides an intriguing explanation as to why women with high caffeine consumption often take longer to conceive than women who do not consume caffeine,” says Professor Ward.

Discovering the link between caffeine consumption and reduced fertility has benefits. “As well as potentially helping women who are finding it difficult to get pregnant, a better understanding of the way Fallopian tubes work will help doctors treat pelvic inflammation and sexually-transmitted disease more successfully,” says Professor Ward. It could also increase our understanding of what causes ectopic pregnancy, an extremely painful and potentially life-threatening situation in which embryos get stuck and start developing inside a woman’s Fallopian tube.

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