~israk mikraj!~

PENGENALAN

Ketika tulisan ini ditulis menunjukkan bahawa bulan Rejab kian hampir melabuhkan tirainya. Maka semakin terasa dekatnya diri ini untuk bertemu dengan bulan mulia lagi penuh rahmat iaitu Ramadhan al-Mubarak. Namun seringkali dilupai bahawa di penghujung bulan Rejab ini berlaku suatu peristiwa yang besar dan penuh bermakna bagi seluruh umat Islam khususnya. Peristiwa yang dimaksudkan ini ialah peristiwa Israk Mikraj yang berlaku pada malam 27 Rejab tahun ke-11 daripada kerasulan Nabi Muhammad S.A.W menurut jumhur ulama.

Terdapatnya sedikit khilaf dalam menentukan tarikh dan waktu sebenar berlakunya peristiwa Israk Mikraj ini sebenarnya. Namun itu bukanlah suatu perkara yang perlu dipanjangkan pedebatannya. Apa yang terlebih penting adalah peristiwa ini benar-benar berlaku kepada Rasulullah S.A.W. kerana ia ada dinyatakan oleh al-Quran al-Karim dan diceritakan sendiri oleh Rasulullah s.a.w. dalam hadisnya yang telah diriwayatkan oleh para ulama secara sahih lagi mutawatir sehingga tidak boleh dipertikaikan lagi.

Matlamat penting daripada peristiwa Israk Mikraj ini adalah pengajaran yang besar apabila Rasulullah S.A.W. dijemput oleh Allah SWT menjadi tetamuNya pada malam yang sangat bersejarah itu. Para ulama telah mencapai kata sepakat bahawa sesiapa yang meragui atau langsung tidak mempercayai peristiwa Israk Mikraj ini maka hukumnya adalah kafir.

Sungguhpun peristiwa luar biasa Israk Mikraj yang terjadi itu nampak mustahil dapat dijangkau oleh alam pemikiran manusia namun selaku umat Islam maka wajib percaya dan yakin bahawa Israk Mikraj yang ditempuhi serta dialami oleh Nabi Muhammad S.A.W. adalah benar dan berlaku dengan roh dan jasadnya sekali. Imam Nawawi menyatakan bahawa perkara sebenar yang telah disepakati para ulama dan begitu juga para sahabat bahawa Nabi Muhammad S.A.W telah diIsrak dan diMikrajkan oleh Allah Taala dengan roh dan jasadnya sekali.

Israk dan Mikraj adalah dua peristiwa yang amat besar dan luar biasa yang dialami oleh Nabi Muhammad S.A.W. dan dianggap sebagai satu penganugerahan yang tinggi nilainya dari segi kerohanian. Kedua-dua peristiwa itu adalah kurnia Allah Taala kepada baginda untuk memperlihatkan tanda-tanda keagungan dan kekuasaanNya. Segala-galanya boleh berlaku dengan kehendak dan kekuasaan Allah Taala selaku Pencipta dan Pentadbir alam semesta.



PENGERTIAN ISRAK DAN MIKRAJ

Israk bererti perjalanan Nabi Muhammad S.A.W. dari Masjid al-Haram di Mekah ke Masjid al-Aqsa di Bait al-Maqdis Palestin. Peristiwa ini ada terakam di dalam Al-Quran.

Firman Allah Taala bermaksud:
Maha Suci Allah yang telah menperjalankan hambaNya (Muhammad) pada suatu malam dari Masjid al-Haram (di Mekah) ke Masjid al-Aqsa (di Palestin) yang telah Kami berkati sekelilingnya agar Kami memperlihatkan kepadanya sebahagian dari tanda-tanda (kekuasaan dan kebesaran) Kami. Sesungguhnya Dia adalah Maha Mendengar lagi Maha Melihat.
(Surah al-Israa: ayat 1).

Sementara itu Mikraj pula merujuk kepada perjalanan Nabi Muhammad S.A.W. dari Masjid al-Aqsa ke Sidrat al-Muntaha di langit ketujuh dekat singgahsana Allah Taala sepertimana yang digambarkan oleh Al-Quran.

Firman Allah Taala bermaksud:
Dan sesungguhnya (Muhammad) telah melihat (Jibril dalam bentuk rupanya yang asal) pada waktu yang lain. (iaitu) Sidrat al-Muntaha. Di dekatnya terletak syurga tempat tinggal (Jannat al-Makwa). (Muhammad melihat Jibril dalam bentuk rupanya yang asal) ketika Sidrat al-Muntaha itu diliputi oleh sesuatu yang meliputinya. Penglihatannya (Muhammad) tidak berpaling daripada yang disaksikannya itu dan tidak (pula) melampauinya. Sesungguhnya dia telah melihat sebahagian tanda-tanda (kekuasaan) TuhanNya yang paling besar.
(Surah an-Najm: ayat 13-18).

Dapatlah disimpulkan di sini bahawa peristiwa Israk Mikraj adalah sebagai satu perjalanan kilat Nabi Muhammad S.A.W. pada malam hari di atas kehendak dan keizinan Allah Taala dari Masjid al-Haram ke Masjid al-Aqsa dan kemudian naik ke langit sampai ke Sidrat al-Muntaha bahkan menembusi tujuh lapis langit lalu kembali semula ke Makkah pada malam yang sama.


SEBAB KEPADA ISRAK MIKRAJ

Bulan Rejab iaitu tahun ke-11 dari kerasulan Nabi Muhammad S.A.W. disifatkan oleh ahli sejarah sebagai tahun dukacita bagi baginda berikutan dengan dua musibah yang menimpa baginda secara berturut-turut. Iaitu kehilangan dua insan yang baginda sayangi berikutan kewafatan Khadijah (isteri baginda) dan kemudian disusuli pula dengan pemergian Abu Talib (bapa saudara baginda).

Musibah yang menimpa itu mempunyai pengaruh besar terhadap diri Nabi Muhammad S.A.W. Baginda merasakan ruang untuk pergerakan dakwah di Makkah semakin sempit dan keselamatan diri turut terancam. Keadaan ini mendorong baginda untuk berpindah ke Thaif dengan harapan agar penduduknya menerima seruan dan bersedia membantu perjuangannya. Namun segala harapan baginda hancur kerana penduduk Thaif bukan saja tidak mahu memberi perlindungan kepada baginda malah baginda dicaci dan dihina dan pelbagai lagi.

Nabi Muhammad S.A.W. kembali semula ke Makkah dengan perasaan hampa dan dukacita. Lalu Allah Taala menganugerahkan Israk Mikraj yang antara lain bertujuan untuk menghibur dan memantapkan iman Nabi Muhammad S.A.W. Sebab kepada Israk Mikraj ini adalah antara sebab musabab berlakunya peristiwa ini namun semuanya di atas kehendak dan ketetapan dari Allah Taala.


PERJALANAN ISRAK DAN MIKRAJ

Telah disebut pada suatu ketika Nabi Muhammad S.A.W. sedang duduk di tepi Kaabah lalu datanglah malaikat Jibril A.S. dengan seekor Buraq untuk membawa Nabi Muhammad S.A.W. dalam peristiwa Israk Mikraj ini. Dari segi bahasa Buraq bererti kilat cahaya. Ia sejenis makhluk menyerupai haiwan. Saiznya besar sedikit dari khimar dan kecil sedikit dari baghal. Buraq dijadikan oleh Allah Taala dari cahaya. Ia boleh melangkah sejauh mata memandang.

Setelah itu berangkatlah Nabi Muhammad S.A.W. dengan ditemani oleh malaikat Jibril A.S. menuju ke Bait al-Maqdis dan baginda solat dua rakaat di situ dan menjadi imam kepada para nabi lain. Setelah selesai solat maka Nabi Muhammad S.A.W. telah dihidangkan dua bejana yang mengandungi dua jenis minuman iaitu satu bejana mengandungi susu dan satu bejana lagi mengandungi arak. Setelah itu Nabi Muhammad S.A.W. mengambil bejana yang mengandungi susu dan tindakan baginda memilih bejana mengandungi susu mendapat sanjungan dari Jibril A.S. kerana menepati fitrah manusia. Kemudian baginda dan Jibril A.S. meneruskan Mikraj ke langit pertama hingga ke tujuh.


KEJADIAN SEPANJANG ISRAK MIKRAJ

Di sini Allah Taala memperlihatkan pelbagai gambaran kejadian aneh dan pelik sebagai balasan dari Allah Taala kepada hamba-hambaNya mengikut apa sahaja perbuatan yang telah dilakukan. Di antara yang kejadian yang diperlihatkan kepada baginda sepanjang Israk dan Mikraj adalah:

Baginda melihat orang yang bercucuktanam mengeluarkan hasil yang banyak dan cepat. Inilah gambaran orang yang membelanjakan harta di jalan Allah Taala.

Baginda mencium bau yang amat wangi dari kubur Masyitah. Ceritanya: Sedang Masyitah menyikat rambut anak Firaun maka sikat yang digunakan itu terjatuh lalu Masyitah menyebut: Dengan nama Allah. Bertanyalah anak Firaun kepada Masitah tentang tuhan selain bapanya. Masyitah menjawab: Tuhanku dan tuhan bapa kamu adalah Allah. Anak Firaun memberitahu bapanya akan hal ini lalu Masyitah diugut oleh Firaun supaya kembali ke agama asalnya. Masyitah enggan dan tetap dengan pendiriannya. Lalu Firaun mencampakkan seorang demi seorang anaknya ke dalam air yang mendidih sehingga tiba giliran anak terakhirnya yang sedang disusui olehnya. Masyitah merasa sangat bimbang dan kesian akan anak kecilnya itu lalu Masyitah cuba melengah-lengahkan masa. Dengan kuasa Allah Taala maka bayi tersebut dapat berkata-kata lalu menyebut: Wahai ibuku! Sesungguhnya azab akhirat itu jauh lebih pedih dari azab dunia maka usahlah ibu menjauh-jauhkan diri kerana ibu di pihak yang benar. Lalu Masyitah melepaskan bayinya dan Firaun dengan segera mencampakkan bayi itu ke dalam didihan air. Masyitah berkata: Aku mempunyai permintaan iaitu supaya engkau (Firaun) mengumpulkan semua tulang dan menanamnya. Firaun berkata: Aku akan melakukannya. Lantas Firaun pun mencampakkan Masyitah ke dalam air didihan itu.

Baginda melihat sekumpulan manusia berpakaian compang-camping sambil memakan sampah-sarap serta rumput. Itulah gambaran golongan manusia yang enggan mengeluarkan zakat dan tidak bersedekah kerana sayangkan harta yang dimiliki.

Baginda melihat sekumpulan manusia yang mempunyai perut yang besar sehingga tidak terdaya lagi untuk bangun dan berdiri. Inilah gambaran manusia yang memakan hasil daripada perbuatan riba.

Baginda melihat sekumpulan manusia yang asyik memakan daging mentah dan busuk sedangkan di sisi mereka juga terdapat daging yang telah dimasak dan berkeadaan baik. Inilah gambaran manusia yang telah melakukan zina dalam hidup mereka sedangkan mereka sudah pun mempunyai isteri yang telah dikahwini secara sah.

Baginda turut melihat sekumpulan manusia yang sedang memecahkan kepalanya sendiri. Inilah gambaran manusia yang terlalu sibuk dengan hal-hal keduniaan sehingga lalai menunaikan kewajipan bersolat.

Baginda melihat sekumpulan manusia yang memotong lidahnya sendiri secara berterusan. Inilah gambaran manusia yang dalam hidup mereka suka menabur fitnah dan berbohong apabila berkata-kata.

Baginda melihat wanita menangis sambil meminta pertolongan tetapi tiada yang sanggup membantu. Inilah gambaran balasan wanita yang berhias bukan kerana suaminya.

Baginda melihat wanita tergantung pada rambutnya serta otaknya menggelegak dalam periuk. Inilah gambaran balasan wanita yang tidak menutup auratnya.

Baginda melihat wanita berkepala seperti babi dan badannya seperti kaldai dan menerima berbagai-bagai balasan. Inilah gambaran wanita yang suka membuat fitnah dan bermusuh dengan jiran dan membuat dusta.


DIFARDHUKAN SOLAT LIMA WAKTU

Daripada pelbagai kejadian yang disaksikan sendiri oleh Rasulullah S.A.W. ini ada suatu hal yang amat besar dan penting yang melibatkan proses peribadatan umatnya iaitu perintah Allah Taala agar melakukan ibadat solat fardu.

Sewaktu tiba di Sidrat al-Muntaha maka Rasulullah S.A.W. telah menerima perintah Allah Taala iaitu perintah melakukan ibadat solat untuk seluruh umatnya sebanyak 50 waktu sehari semalam. Sebaik sahaja menerima perintah tersebut tanpa banyak bicara baginda dan Jibril A.S. bersiap sedia untuk turun ke bumi.

Pada masa inilah baginda bertemu dengan Nabi Musa A.S. yang bertanyakan hal itu kepada baginda. Setelah mendengar penjelasan Nabi Muhammad S.A.W. maka Nabi Musa A.S. berkata: Kembalilah kepada Tuhanmu dan mintalah sedikit keringanan kerana bilangan tersebut tidak akan terdaya dilakukan oleh umatmu.

Nabi Muhammad S.A.W. dan Jibril kembali mengadap Allah Taala. Jumlah bilangan waktu solat telah dikurangkan kepada 40 waktu. Apabila berjumpa Nabi Musa A.S. kemudiannya maka Nabi Musa A.S. meminta baginda kembali menemui Tuhan untuk meminta dikurangkan lagi jumlah tersebut. Setelah beberapa kali Nabi Muhammad S.A.W. berulang alik menemui Allah Taala dan pada akhirnya Allah Taala telah mengurangkan bilangan solat fardu tersebut menjadi 5 waktu sahaja.

Apabila kembali semula maka Nabi Musa A.S. masih merasakan umat Nabi Muhammad S.A.W. masih tidak terdaya untuk melakukannya dengan bilangan 5 itu. Nabi Muhammad S.A.W. menyatakan bahawa beliau tidak akan mengadap Allah Taala lagi untuk memintaNya mengurangkan bilangan solat itu kerana baginda merasa malu untuk berdepan dengan Allah Taala.


PERTIKAIAN KAFIR QURAISY

Tiada alasan untuk menolak hakikat peristiwa Israk Mikraj yang dilalui oleh Nabi Muhammad S.A.W. dengan roh dan jasadnya sekali kerana baginda telah diIsrak dan diMikrajkan oleh Allah Taala. Sekalipun peristiwa Israk Mikraj itu adalah perkara luar biasa di sisi akal manusia tetapi bagi Allah Taala Yang Maha Berkuasa maka Dia boleh melakukan apa jua perkara yang dianggap pelik menjadi perkara biasa dan tiada yang mustahil bagiNya.

Kalaulah peristiwa Israk Mikraj itu sekadar mimpi Nabi Muhammad S.A.W pergi ke Bait al-Maqdis dan juga mimpi naik ke langit tujuh maka kaum musyrikin Makkah tidak akan marah dan mempersenda baginda kerana mimpi adalah perkara biasa bagi semua orang. Bilamana kafir Quraisy menentang habis-habisan dan berusaha mati-matian menyangkal peristiwa Israk Mikraj yang berlaku dengan roh dan juga jasad Nabi Muhammad S.A.W. ini bererti dengan sendirinya mereka mengakui bahawa baginda telah diIsrak dan diMikrajkan dengan roh dan jasadnya sekali. Ini kerana mimpi bukanlah suatu yang luar biasa dan tidak menyebabkan orang bersengketa mempertikaikan jika ada orang yang mendakwa sedemikian rupa.

Sekiranya Nabi Muhammad S.A.W itu sekadar mimpi naik ke langit sahaja maka tidak ada mustahaknya orang-orang kafir Quraisy mencabar baginda untuk membuktikan kebenaran ceritanya dengan menanyakan baginda berkenaan rupabentuk Masjid al-Aqsa serta jumlah pintu dan tiangnya dan juga perkara-perkara yang berkaitan dengan masjid tersebut.

Pertanyaan kafir Quraisy mengenai keadaan rupabentuk Masjid al-Aqsa dengan tujuan untuk memerangkap Nabi Muhammad S.A.W. kerana mereka yakin seratus peratus bahawa baginda tidak pernah menjejakkan kaki ke Bait al-Maqdis. Sebaliknya apabila semua pertanyaan telah dijawab dengan betul maka mereka menjadi panik dan bingung. Mereka tahu bahawa Nabi Muhammad S.A.W. sebelum peristiwa ini sememangnya tidak pernah pergi ke Bait al-Maqdis tetapi mereka hairan bagaimana baginda boleh menjawab semua pertanyaan berhubung Masjid al-Aqsa itu dengan tepat. Mereka telah hilang punca dan mereka terpaksa membuat tuduhan bahawa Nabi Muhammad S.A.W. adalah seorang ahli sihir.

Sememangnya tiada dalam ingatan Nabi Muhamamd S.A.W. tentang rupabentuk Masjid al-Aqsa kerana baginda sekadar dibawa singgah sebentar oleh Jibril A.S. untuk menunaikan solat dua rakaat. Bagaimanapun Allah Taala tidak akan membiarkan RasulNya terperangkap dalam percaturan jahat puak musyrikin Makkah yang cuba hendak memalukan baginda. Allah Taala datangkan Masjid al-Aqsa ke hadapan Nabi Muhammad S.A.W. Justeru itu Nabi Muhammad S.A.W. dapat melihat Masjid al-Aqsa dengan jelas sehingga mudah untuk baginda menjawab semua pertanyaan puak musyrikin.

Orang yang beriman akan terus beriman dan makin bertambah kukuhlah iman mereka. Manakala orang yang tidak beriman akan terus kufur bersama kekufuran mereka. Semuanya telah dibentangkan di depan mata.


PENUTUP

Dari segala apa yang telah saya nyatakan ini maka sudah tentulah pelbagai pengajaran dapat diambil dari peristiwa Israk Mikraj ini. Ia bukanlah hanya sekadar cerita untuk didengar dan dibaca semata-mata namun jauh dari itu ia dapat dijadikan pedoman hidup selama kita di dunia ini. Semoga kita semua mendapat manfaat dari tulisan ringkas ini. InsyaAllah.


buluh.iluvislam.com.

Wallahualam.

Hyperemesis gravidarum

Hyperemesis gravidarum (HG) is a severe form of morning sickness, with "unrelenting, excessive pregnancy-related nausea and/or vomiting that prevents adequate intake of food and fluids."[1] Hyperemesis is considered a rare complication of pregnancy but, because nausea and vomiting during pregnancy exist on a continuum, there is often not a good diagnosis between common morning sickness and hyperemesis. Estimates of the percentage of pregnant women afflicted range from 0.3% to 2.0%.

Etymology
Hyperemesis gravidarum is from the Greek hyper-, meaning excessive, and emesis, meaning vomiting, as well as the Latin gravida, meaning pregnant. Therefore, hyperemesis gravidarum means "excessive vomiting in pregnancy."

Cause
The cause of HG is unknown. The leading theories speculate that it is an adverse reaction to the hormonal changes of pregnancy. In particular Hyperemesis may be due to raised levels of beta HCG (human chorionic gonadotrophin)[3] as it is more common in multiple pregnancies and in gestational trophoblastic disease. This theory would also explain why hyperemesis gravidarum is most frequently encountered in first trimester (often around 8 – 12 weeks of gestation), as HCG levels are highest at that time and decline afterwards.

Additional theories point to high levels of estrogen and progesterone[citation needed], which may also be to blame for hypersalivation; decreased gastric motility (slowed emptying of the stomach and intestines); immune response to fragments of chorionic villi that enter the maternal bloodstream; or immune response to the "foreign" fetus.[citation needed]

There is also evidence that leptin may play a role in HG.

Historically, HG was blamed upon a psychological condition of the pregnant women. Medical professionals believed it was a reaction to an unwanted pregnancy or some other emotional or psychological problem.[citation needed] This theory has been disproved, but unfortunately some medical professionals espouse this view and fail to give patients the care they need.[citation needed]

A recent study gives "preliminary evidence" that there may be a genetic component.

Symptoms
When HG is severe and/or inadequately treated, it may result in:

Loss of 5% or more of pre-pregnancy body weight
Dehydration, causing ketosis and constipation
Nutritional deficiencies
Metabolic imbalances
Altered sense of taste
Sensitivity of the brain to motion
Food leaving the stomach more slowly
Rapidly changing hormone levels during pregnancy
Stomach contents moving back up from the stomach
Physical and emotional stress of pregnancy on the body
Subconjunctival hemorrhage (broken blood vessels in the eyes)
Difficulty with daily activities
Hallucinations
Some women with HG lose as much as 20% of their body weight. Many sufferers of HG are extremely sensitive to odors in their environment; certain smells may exacerbate symptoms. This is known as hyperolfaction. Ptyalism, or hypersalivation, is another symptom experienced by some women suffering from HG.

As compared to morning sickness, HG tends to begin somewhat earlier in the pregnancy and last significantly longer. While most women will experience near-complete relief of morning sickness symptoms near the beginning of their second trimester, some sufferers of HG will experience severe symptoms until they give birth to their baby, and sometimes even after giving birth. An overview of the significant differences between morning sickness and HG can be found at Hyperemesis or Morning Sickness: Overview.

Complications
For the pregnant woman
If inadequately treated, HG can cause renal failure, central pontine myelinolysis, coagulopathy, atrophy, Mallory-Weiss syndrome, hypoglycemia, jaundice, malnutrition, Wernicke's encephalopathy, pneumomediastinum, rhabdomyolysis, deconditioning, splenic avulsion, and vasospasms of cerebral arteries. Depression is a common secondary complication of HG.

For the fetus
No long-term follow-up studies have been conducted on children of hyperemetic women. Children born to hyperemetic women appear to have no greater risk of complications or birth defects than the general population. However, recent research in fetal programming indicates that prolonged stress, dehydration and malnutrition during pregnancy can put the fetus at risk for chronic disease, such as diabetes or heart disease, later in life, or neurobehaviorial issues from birth. This underscores the importance of aggressive treatment of the condition.

Diagnosis
Women who are experiencing hyperemesis gravidarum often are dehydrated and losing weight despite efforts to eat. The nausea and vomiting begins in the first or second month of pregnancy. It is extreme and is not helped by normal measures.

Fever, abdominal pain, or late onset of nausea and vomiting usually indicate another condition, such as appendicitis, gallbladder disorders, gastritis, hepatitis, or infection and the vomiting is involuntary.

Treatment
Because of the potential for severe dehydration and other complications, HG is generally treated as a medical emergency. Treatment of HG may include antiemetic medications and intravenous rehydration. If medication and IV hydration are insufficient, nutritional support may be required.

Management of HG can be complicated because not all women respond to treatment. Coping strategies for uncomplicated morning sickness, which may include eating a bland diet and eating before rising in the morning, may be of some assistance but are unlikely to resolve the disorder on their own. There is evidence that ginger may be effective in treating pregnancy-related nausea; however, this is generally ineffective in cases of HG.

IV hydration
IV hydration often includes supplementation of electrolytes as persistent vomiting frequently leads to a deficiency. Likewise supplementation for lost thiamine (Vitamin B1) must be considered to reduce the risk of Wernicke's encephalopathy. A and B vitamins are depleted within two weeks, so extended malnutrition indicates a need for evaluation and supplementation. Additionally, mineral levels should be monitored and supplemented; of particular concern are sodium and potassium.

After IV rehydration is completed, patients generally progress to frequent small liquid or bland meals. After rehydration, treatment focuses on managing symptoms to allow normal intake of food. However, cycles of hydration and dehydration can occur, making continuing care necessary. Home care is available in the form of a PICC line for hydration and nutrition (called total parenteral nutrition). Home treatment is often less expensive than long-term and/or repeated hospital stays.

Medications
While no medication is considered completely risk-free for use during pregnancy, there are several which are commonly used to treat HG and are believed to be safe.

The standard treatment in most of the world is Benedictin (also sold under the trademark name Diclectin), a combination of doxylamine succinate and vitamin B6. However, due to a series of birth-defect lawsuits in the United States against its maker, Merrill Dow, Benedictin is not currently on the market in the U.S. (None of the lawsuits were successful, and numerous independent studies and the Food and Drug Administration (FDA) have concluded that Benedictin does not cause birth defects.) Its component ingredients are available over-the-counter (doxylamine succinate is the active ingredient in many sleep medications), and some doctors will recommend this treatment to their patients.

Antiemetic drugs, especially ondansetron (Zofran), are effective in many women. The major drawback of ondansetron has been its cost. In severe cases of HG, the Zofran pump may be more effective than tablets. Zofran is also available in ODT (oral disintegrating tablet) which can be easier for women who have trouble swallowing due to the nausea. Promethazine (Phenergan) has been shown to be safe, at least in rats and may be used during pregnancy with minimal/no side effects.Metoclopramide is sometimes used in conjunction with antiemetic drugs; however, it has a somewhat higher incidence of side effects. Other medications less commonly used to treat HG include Marinol, corticosteroids and antihistamines.

Nutritional support
Women who do not respond to IV rehydration and medication may require nutritional support. Patients might receive parenteral nutrition (intravenous feeding via a PICC line) or enteral nutrition (via a nasogastric tube or a nasojejunum tube).

Support
It is important that women get early and aggressive care during pregnancy. This can help limit the complications of HG. Also, because depression can be a secondary condition of HG, emotional support, and sometimes even counseling, can be of benefit. It is important, however, that women not be stigmatized by the suggestion that the disease is being caused by psychological issues.

~placental abruption~

If the placenta peels away from the inner wall of the uterus before delivery — either partially or completely — it's known as placental abruption (abruptio placentae).
Placental abruption is an uncommon and serious complication of pregnancy.It occurs in 1% of pregnancies world wide with a fetal mortality rate of 20-40% depending on the degree of separation. Placental abruption is also a significant contributor to maternal mortality.

Placental abruption can deprive the baby of oxygen and nutrients and cause heavy bleeding in the mother.
Trauma, hypertension, or coagulopathy contributes to the avulsion of the anchoring placental villi from the expanding lower uterine segment, which in turn, leads to bleeding into the decidua basalis. This can push the placenta away from the uterus and cause further bleeding.Women may present with vaginal bleeding, abdominal or back pain, abnormal or premature contractions, fetal distress or death.

What is LA??

Lactococcus is a genus of lactic acid bacteria that were formerly included in the genus Streptococcus Group N1. They are known as homofermentors meaning that they produce a single product, lactic acid in this case, as the major or only product of glucose fermentation. Their homofermentative character can be altered by adjusting cultural conditions like pH, glucose concentration, and nutrient limitation. They are gram-positive, catalase negative, non-motile cocci that are found singly, in pairs, or in chains. The genus contains strains known to grow at or below 7˚C.

Five species of Lactococcus are currently recognized along with three subspecies. They are:

L. lactis
L. lactis subsp. lactis
L. lactis subsp. cremoris
L. lactis subsp. hordniae
L. garvieae
L. plantarum
L. raffinolactis
L. piscium

These organisms are commonly used in the dairy industry in the manufacture of fermented dairy products like cheeses. They can be used in single strain starter cultures, or in mixed strain cultures with other lactic acid bacteria such as Lactobacillus and Streptococcus. Special interest is placed on the study of L. lactis subsp. lactis and L. lactis subsp. cremoris as they are the strains used as starter cultures in industrial dairy fermentations. Their main purpose in dairy production is the rapid acidification of milk; this causes a drop in the pH of the fermented product which prevents the growth of spoilage bacteria. The bacteria also play a role in the flavor of the final product. Lactococci are currently being used in the biotechnology industry. They are easily grown at industrial scale up on cheap whey based media. As food grade bacteria they are used in the production of foreign proteins that are applied to the food industry.

Lactococcus lactis is a Gram-positive bacteria used extensively in the production of buttermilk and cheese. L. lactis are cocci that group in pairs and short chains, and depending on growth conditions appears ovoid with typically 0.5 - 1.5 µm in length. L. lactis do not produce spores (non-sporulating) and are not motile (non-motile). They have a homo-fermentative metabolism and have been reported to produce exclusively L(+) lactic acid.However, reported that D(-) lactic acid can be produced when cultured at low pH. The capability to produce lactic acid is one of the reasons why Lactococcus lactis is one of the most important micro-organisms involved in the dairy industry. Generally, it has been considered as an opportunistic pathogen. Even though, the number of clinical cases associated with infections by these microorganisms has increased in the last decade in both humans and animals. L. lactis is a bacterium which has a crucial importance for manufacturing dairy products such as buttermilk and cheeses. When L. lactis ssp. lactis is added to milk, the bacterium uses enzymes to produce energy molecules, called ATP, from lactose.The byproduct of ATP energy production is lactic acid. The lactic acid produced by the bacterium curdles the milk that then separates to form curds, which are used to produce cheese.

Other uses that have been reported for this bacteria include the production of pickled vegetables, beer or wine, some breads and other fermented food-stuffs such as soymilk kefir, buttermilk, .... Nowadays, researchers believe that understanding the physiology and genetic make-up of this bacterium will provide food manufacturers as well as the pharmaceutical industry with invaluable benefits

Lactococcus lactis
Scientific classification
Kingdom: Bacteria
Division: Firmicutes
Class: Bacilli
Order: Lactobacillales
Family: Streptococcaceae
Genus: Lactococcus
Species: L. lactis
Binomial name
Lactococcus lactis
(Lister 1873)
Schleifer et al. 1986
Subspecies

L. l. cremoris
L. l. hordniae
L. l. lactis
L. l. lactis bv. diacetylactis

Protein Data Bank

The Protein Data Bank (PDB) is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids. (See also crystallographic database). The data, typically obtained by X-ray crystallography or NMR spectroscopy and submitted by biologists and biochemists from around the world, can be accessed at no charge on the internet. The PDB is overseen by an organization called the Worldwide Protein Data Bank, wwPDB.

The PDB is a key resource in areas of structural biology, such as structural genomics. Most major scientific journals, and some funding agencies, such as the NIH in the USA, now require scientists to submit their structure data to the PDB. If the contents of the PDB are thought of as primary data, then there are hundreds of derived (i.e., secondary) databases that categorize the data differently. For example, both SCOP and CATH categorize structures according to type of structure and assumed evolutionary relations; GO categorize structures based on genes.

History

The PDB originated as a grassroots effort.In 1971, Walter Hamilton of the Brookhaven National Laboratory agreed to set up the data bank at Brookhaven. Upon Hamilton's death in 1973, Tom Koeztle took over direction of the PDB. In January 1994, Joel Sussman was appointed head of the PDB. In October 1998,the PDB was transferred to the Research Collaboratory for Structural Bioinformatics (RCSB); the transfer was completed in June 1999. The new director was Helen M. Berman of Rutgers University (one of the member institutions of the RCSB). In 2003, with the formation of the wwPDB, the PDB became an international organization. Each of the four members of wwPDB can act as deposition, data processing and distribution centers for PDB data. The data processing refers to the fact that wwPDB staff review and annotates each submitted entry. The data are then automatically checked for plausibility.

The PDB database is updated weekly (on Tuesday). Likewise, the PDB Holdings List is also updated weekly. As of 23 February 2010 (2010 -02-23)[update], the breakdown of current holdings was as follows:

Experimental
Method Proteins Nucleic Acids Protein/Nucleic Acid
complexes Other Total
X-ray diffraction 51291 1193 2368 17 54869
NMR 7206 891 152 7 8256
Electron microscopy 184 17 71 0 272
Hybrid 18 1 1 1 21
Other 120 4 4 13 141
Total: 58819 2106 2596 38 63559

44,233 structures in the PDB have a structure factor file.
5,546 structures have an NMR restraint file.

These data show that most structures are determined by X-ray diffraction, but about 15% of structures are now determined by protein NMR, and a few are even determined by cryo-electron microscopy.

The significance of the structure factor files, mentioned above, is that, for PDB structures determined by X-ray diffraction that have a structure file, the electron density map may be viewed. The data of such structures is stored on the "electron density server", where the electron maps can be viewed.

In the past, the number of structures in the PDB has grown nearly exponentially. In 2007, 7263 structures were added. However, in 2008, only 7073 structures were added, so the rate of production of structures has appeared to start to decrease. And yet, in 2009, 7448 structures were added, the highest ever for any year.

The file format initially used by the PDB was called the PDB file format. This original format was restricted by the width of computer punch cards to 80 characters per line. Around 1996, the "macromolecular Crystallographic Information file" format, mmCIF, started to be phased in. An XML version of this format, called PDBML, was described in 2005.The structure files can be downloaded in any of these three formats. In fact, individual files are easily downloaded into graphics packages using web addresses:

* For PDB format files, use, e.g., http://www.pdb.org/pdb/files/4hhb.pdb.gz
* For PDBML (XML) files, use, e.g., http://www.pdb.org/pdb/files/4hhb.xml.gz

The "4hhb" is the PDB identifier. Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. (This cannot be used as an identifier for biomolecules, because often several structures for the same molecule—in different environments or conformations—are contained in PDB with different PDB IDs.)

HTRA

Maintenance of a protein in a properly folded state is important for many of its functions. Cells therefore contain molecules, such as chaperones and proteases, to refold or rid themselves of misfolded and aggregated proteins. Chaperones recognize and bind proteins in nonnative states by interacting with their surface-exposed hydrophobic groups, holding the proteins in such a way that they may refold. Proteins that cannot be recovered are targeted for proteolytic destruction. Although chaperones and proteases carry out antagonistic functions, the substrates that they bind and act on are similar, and it is likely that they are coordinately regulated. For example, the bacterial proteins ClpP and ClpA (or X) form heterooligomeric complexes containing both protease (ClpP) and chaperone (ClpA or X) functions . Another remarkable example is the HtrA (high-temperature requirement) family of stress-induced proteins, where both activities exist within a single protein and the switch from protease to chaperone is regulated in a temperature-dependent manner.

In multicellular organisms, programmed cell death (apoptosis) is used to remove excess, damaged, or infected cells. The key effector proteases of apoptosis are caspases which remain in a latent form in healthy cells. While caspase activation can be regulated by members of the Bcl-2 family, once activated, caspases can be controlled by binding directly to members of the inhibitor of apoptosis (IAP) family of proteins. The IAPs can themselves be antagonized by proapoptotic proteins that bind to them, displacing the active caspases. For example, upon receipt of an apoptotic signal, the mitochondrial protein DIABLO/Smac is released into the cytosol where it binds to XIAP, thereby displacing processed caspases 9 and 3. DIABLO contains a conserved N-terminal motif (AVPI), similar to that found in Drosophila IAP antagonists, which is required for binding to IAPs. Recently, screens for other regulators of IAPs identified another mitochondrial protein, HtrA2, a mammalian protein that bears the serine protease and PDZ domain of its bacterial counterpart [3, 4, 5, 6 and 7]. Upon release from the mitochondrial intermembrane space, HtrA2 interacts with XIAP in a similar way to DIABLO. However, for maximal induction of apoptosis, overexpressed HtrA2 requires both its protease activity and its AVP amino terminus.

So how can HtrA act as a protease, chaperone, and regulator of apoptosis? Two recent papers describing the crystal structures of the bacterial periplasmic protein, DegP [8] and the mammalian homolog, HtrA2 [9] go some way toward elucidating the mechanism by which they might function. As predicted, each monomer of the E. coli HtrA, DegP, consists of three distinct domains, an N-terminal protease domain and two C-terminal PDZ domains. Three monomers come together, mediated by extensive contacts between the protease domains to form a trimeric ring, and this then forms a hexameric structure by staggered association of two trimers (see Figure 1, panel A). Two distinct hexameric molecules of DegP are apparent in the asymmetric unit, one in an “open form” and the other in a “closed form.” The primary contacts between the trimers are three pillars that are formed by interaction of the two N-terminal β strands from opposing monomers (see Figure, panel A). In the closed form shown in the figure, an additional set of interactions between the trimers occurs via the PDZ domains. However, these interactions involve flexible parts of the structure, and the hexamer is best described as a “dimer of trimers.”



















The molecules were aligned on the protease domain. The left and right images are related by a 90° rotation about the horizontal axis for both molecules.

(A) Structure of the “closed” DegP hexamer (Protein Data Bank code 1KY9). One trimer (orange, yellow, and gray) is shown as a surface representation while in the second trimer, two monomers (green and blue) are shown as a surface and the third as a ribbon. The protease domain (red), PDZ1 domain (purple), and PDZ2 (light pink) are colored separately; the catalytic serine is obscured in these views. The pillar is labeled P and the N and C termini are labeled N and C, respectively.

(B) Structure of the HtrA2 trimer (Protein Data Bank code 1LCY). Two monomers are shown as a surface representation. The third monomer is shown as a ribbon. The protease domain (red) and the PDZ domain (light pink) are colored separately; the site of the catalytic serine is shown (S) and the N and C termini are labeled accordingly.


In the structure of DegP solved by Krojer et al. [8], the critical serine in the catalytic triad was mutated to alanine in order to prevent autoproteolysis, and the structure was solved at 4°C to lock it in the chaperone conformation. As a result, although the general location of the active site is similar to that observed for other serine proteases, the catalytic triad is in an inactive conformation and access to the active site is precluded by a loop from an opposing monomer. A large conformational change is required before substrates can access the active site. This conformational change may be regulated in part by the PDZ domains. The PDZ domains are highly flexible and appear to act as gatekeepers of the catalytic site. In the chaperone conformation solved here, it is expected that partially unfolded substrates will be fed into the central cavity through lateral pores that occur in the open conformation. Once inside, substrates will interact with hydrophobic residues in the protease domain. Unlike other chaperones, ATP does not drive binding and release, and the mechanism by which this cycle is regulated in DegP is unknown. Perhaps rigid body movement of the PDZ domains is involved.

Shi and his colleagues have solved the crystal structures of a number of important proteins involved in apoptosis in recent years. In the latest paper, by Li et al. [9], they now report the structure of mature HtrA2, the mammalian counterpart of DegP. As predicted, this structure is homologous to that of bacterial HtrAs; in particular, the protease domain is highly conserved and the catalytic triad has a similar position between the two lobes of the protease domain (see Figure, panel B). Furthermore, access to the catalytic site is blocked by the PDZ domain and like DegP, the structure solved here is inactive. The regions of HtrA2 involved in trimer formation also adopt a very similar conformation to that seen in DegP, and the trimeric structure is conserved (see Figure, panel B). However, HtrA2 has several deletions when compared to DegP; for example, the N-terminal β strands that form the pillars in DegP are truncated and the first PDZ domain has been deleted. As a consequence of these deletions, HtrA2 only assembles into trimers and does not form hexamers. What is the consequence of no longer being a hexamer? The buried nature of the protease active site in DegP is likely to be important for its duality of function. Does loss of an enclosed cage mean that HtrA2 can no longer function as a chaperone? This is an important question that will require further studies. Other features of the HtrA2 structure are more revealing. For instance, the N terminus of HtrA2 is accessible from the top of the trimer, and if HtrA2 were released from the mitochondria it would be free to interact with IAPs in a manner similar to that seen for DIABLO [10], although it is uncertain whether all HtrA2 monomers would interact with IAPs. The structure of the PDZ domain in HtrA2 is also remarkable because, like bacterial PDZ domains, it is circularly permuted relative to mammalian PDZ domains. This likely reflects the bacterial ancestry of HtrA2.

Do PDZ domains hold the key to regulating HtrA proteases? PDZ domains are important in signal transduction and cellular organization. They bind an array of target proteins through small C-terminal motifs and play roles in the transport, localization, and assembly of these proteins [11]. What is their role in the HtrA proteases? In the cases of DegP and HtrA2, their role is probably not in the assembly of the oligomer, but in the recognition of short motifs for delivery to the proteolytic or chaperone activities of the protease domain. They also appear to act as modulators of activity. Deletion of the PDZ domains from DegP removed the catalytic activity but not the chaperone activity [2], whereas in HtrA2 deletion of the PDZ domain activated the protease [9]. To further understand the role of these domains, structures of complexes between HtrA proteins and substrates are required.

In conclusion, the crystal structures of DegP and HtrA2 have elegantly revealed the structural differences and similarities between these two proteins. However, many questions about their function remain unresolved. What is the function of HtrA2 in mitochondria? Does it perform the same role as DegP in E. coli? Is HtrA2 important for apoptotic function in vivo? It will be interesting to see whether HtrA2 knockout animals have a phenotype that resembles a mitochondrialopathy, suggesting that it is in the mitochondria that it has its primary role, or whether their phenotype resembles those of apaf-1 or caspase 9 knockouts, suggesting its primary role is to regulate cell death. HtrA2 can clearly interact with IAPs but the significance of this interaction is uncertain, as the protease activity is also required to fully induce apoptosis. Identification of the targets of the protease might provide clues as to the importance of HtrA2. Questions about the regulation of DegP also remain unresolved, although the structures allow hypotheses to be proposed and tested.

Serine protease HTRA2, mitochondrial is an enzyme that in humans is encoded by the HTRA2 gene. This gene encodes a serine protease. HtrA2, also known as Omi, is a mitochondrially-located serine protease. HtrA2 can be released from the mitochondria during apoptosis and uses its four most N-terminal amino acids to mimic a caspase and be recruited by IAP caspase inhibitors such as XIAP and CIAP1/2. Once bound, the serine protease cleaves the IAP, reducing the cell's inhibition to caspase activation. Additionally, HtrA2 has a PDZ domain, though little is known about its ability to bind PDZ binding motif peptides. HtrA2 has recently been identified as a gene related to Parkinson's disease. Mutations in Htra2 have been found in patients suffering from Parkinson's disease. Additionally, mice lacking HtrA2 have a parkinsonian phenotype. This suggests that HtrA2 is linked to Parkinson's disease progression in humans and mice.

HtrA2 shows similarities with DegS, a bacterial protease present in the periplasm of gram-negative bacteria. Structurally, HtrA2 is a trimeric molecule with central protease domains and carboxy-terminal PDZ domains.

What is LexA??

Repressor LexA or LexA is a repressor enzyme (EC 3.4.21.88) that represses SOS response genes coding for DNA polymerases required for repairing DNA damage. LexA is intimately linked to RecA in the biochemical cycle of DNA damage and repair. RecA binds to DNA-bound LexA causing LexA to cleave itself in a process called autoproteolysis.

DNA damage can be inflicted by the action of antibiotics. Bacteria require topoisomerases such as DNA gyrase or topoisomerase IV for DNA replication. Antibiotics such as ciprofloxacin are able to prevent the action of these molecules by attaching themselves to the gyrase - DNA complex. This is counteracted by the polymerase repair molecules from the SOS response. Unfortunately the action is partly counterproductive because ciprofloxacin is also involved in the synthetic pathway to RecA type molecules which means that the bacteria responds to an antibiotic by starting to produce more repair proteins. These repair proteins can lead to eventual benevolent mutations which can render the bacteria resistant to ciprofloxacin.

Mutations are traditionally thought of as happening as a random process and as a liability to the organism. Many strategies exist in a cell to curb the rate of mutations. Mutations on the other hand can also be part of a survival strategy. For the bacteria under attack from an antibiotic, mutations help to develop the right biochemistry needed for defense. Certain polymerases in the SOS pathway are error-prone in their copying of DNA which leads to mutations. While these mutations are often lethal to the cell, they can also lead to mutations which improve the bacteria's survival. In the specific case of topoisomerases, some bacteria have mutated one of their amino acids so that the ciproflaxin can only create a weak bond to the topoisomerase. This is one of the methods that bacteria use to become resistant to antibiotics.

Impaired LexA proteolysis has been shown to interfere with ciprofloxacin resistance.[1] This offers potential for combination therapy that combine quinolones with strategies aimed at interfering with the action of LexA either directly, or via RecA.