Ibn Rajab

This Wordpress is in Malay and contains some of my articles. They seem different when re-written in Malay:
http://ibnrajab.wordpress.com/2008/07/27/info-kesihatan/

How to Dissolve Gallstones

Hempedu Update

12 Ramadan 1434 Hijrah

21 July 2013

This is a miracle - the 2 gallstones have disappeared!
Alhamdulillah.
How did it happen?
What did I do?
How I did it?

Here is the miracle cure for gallstones, I did it my way:

1. Eat less for buka puasa for 2 days.
2. Feel where the gallbladder is - right side, just under the last rib
3. After buka puasa, after solat maghrib, rub Minsyam minyak zaitun. Rub over a big area, to cover all possible areas where pain could arise.
4. Then rub a fresh tube of halia bara (an old tube won't work as the menthol content is gone). The halia bara will heat up and the hot sensation can be felt but it doesn't burn the skin. 
5. This is what I think happened: This hot-cold sensation will open up the sphincter of the gallbladder somewhat. 
6. This is how I think the 2 big gallstones got out: The 2 gallstones are elongated and will align properly, and flow out of the gallbladder, one by one, big as they maybe, but they will still move out. Update 22 August 2013: I take olive oil softgel to soften the bile duct and also to help dissolve the gallstone. Dr Lim Ju Boo also recommends to take olive oil to soften the bile duct and help the gallstones dissolve.
7. How long did it take for the gallstones to move out? I think for me it took 2 days. It took 2 days for the 2 gallstones to move out. The pain was felt first in the right side and then in the left side, and then it disappeared altogether. I can breathe normally and am not in pain.
8. I think probably the 2 gallstones dissolved along the way out through the biliary track, or became small enough to flow through the biliary duct and out into the duodenum.

Today is the second day after the 2 gallstones moved out from the gallbladder. The gallbladder feels empty and soft now, not swollen and painful as before. 

Once the 2 gallstones moved out, I was able to take more food at buka puasa, without pain or feeling bloated - just feels normal. It felt so rewarding, Alhamdulillah.

Also, I stayed up late at night, and before I went to bed, I took hot coffee and 3 dates, to fill up the gut so that the bile would continue to flow and empty out and not collect in the gallbladder. I think when the gut is empty for a long time, the gallbladder has time to refill and concentrate fast. So having dates in the gut takes care of continued bile flow into the duodenum.

I also took a herbal drink that needed honey (good quality honey) and maybe that too helped. I know honey stimulates the gut and makes the enzymes active. I don't know how it affects bile and bile flow but it seems to work in synergy.

Tonight is the second night I'm taking coffee and dates late at night. This seems quite an interesting mix as I have never taken this before. I take 2 types of coffee - Super Coffee (regular, 3-in-1, low fat) and Kopiko (3-in-1). I make a tumbler-full of one coffee and a tall cup of the other coffee. I think the type of coffee matters. It didn't work with Nescafe or TESCO coffee - they were hopeless. I have not gone back to these 2 coffee brands.

I consumed Yusuf Taiyub high quality dates - these are half brown and half creamy (rutab). I read that this type of dates are good for the internal system (gut), so I used them. I received these dates from Assoc Prof Dr Sirajudeen in my dept. There are 38 known varieties of dates.

I'm trying another type of dates tonight as yesterday's dates are all gone. Tonight, I'm trying Gurun Emas dates which are coated with Habbatus sauda. Tonight, I'm taking 3 dates, 2 dried seedless prunes and 1 tablespoonful of dried cranberries, with coffee. I had a ripe banana at buka puasa, 5 hours ago. Bananas are not good for midnight snacks.

InsyaAllah, this is the easiest way to dissolve gallstones.
I haven't gone to scan yet. I hope the gallstones are gone for good.
I will teach the doa later.
Hope that helps gallstone suffers.

Update (12 October 2014): The "two gallstones" detected by ultrasound were actually one large piece of U-shaped cholesterol gallstone. It was removed by laparoscopic cholecystectomy as it was too big to be dissolved by traditional or non surgical methods and moreover, would take too long to dissolve.

External link:
http://www.healthline.com/health/gallstones#Overview1

Orthodontics

Crossbite —The condition in which the upper teeth bite inside the lower teeth.

Crown —The natural part of the tooth covered by enamel. A restorative crown is a protective shell that fits over a tooth.

Deep bite —A closed bite; a deep or excessive overbite in which the lower incisors bite too closely to or into the gum tissue or palate behind the upper teeth.

Eruption —The process of a tooth breaking through the gum tissue to grow into place in the mouth.

Impacted tooth —Any tooth that is prevented from reaching its normal position in the mouth by another tooth, bone, or soft tissue.

Incisors —The eight front teeth.

Interceptive orthodontics —Preventative orthodontics; early, simpler orthodontic treatment.

Malocclusion —The misalignment of opposing teeth in the upper and lower jaws.

Molars —The teeth behind the primary canines or the permanent premolars, with large crowns and broad chewing surfaces for grinding food.

Open bite —A malocclusion in which some teeth do not meet the opposing teeth.

Orthognatic surgery —Surgery to alter the relationships of the teeth and/or supporting bones, usually in conjunction with orthodontic treatment.

Overbite —Protrusion of the upper teeth over the lower teeth.

Plaque —A sticky film of saliva, food particles, and bacteria that attaches to the tooth surface and causes decay.

Retainer —An orthodontic appliance that is worn to stabilize teeth in a new position.



Source:
http://www.encyclopedia.com/topic/orthodontics.aspx

How to be a top student

I will share with everyone about how I made it from being just an ordinary student to being the top student anywhere and everywhere.

Life as an Ordinary Student
As an ordinary student, life was dull. You do as you're told. Everybody dictates and you follow. Otherwise you get a scolding. I was the average ordinary student. I hated it! I hated being told and ordered around. I wanted change. I wanted to do things that I like and doing things my own way. I didn't want people to tell me what to do. Why do people have to tell me what to do? I am in charge of my own life and I will direct my own life. I need to change and be a director for my own life.

The Change
Change is a big messy word that nobody really understands. Ask anybody what that word means and nobody can even define what it is. Change is essentially self-directed steps that I wanted to take to make my life different, and in the end I become my own independent director. I will be in charge of my own self and my own life. No need to be told what to do. Even my parents don't have to check on me whether I'm studying or failing. I will be my own director.

How to Change
Good question. There are a 1001 ways to create change. For me, the easiest way to make change is to change whatever I'm doing. In creating change, I need to be able to do more than what I usually do. If I read one page of a textbook, I now need to read 2 pages. That's called change. If I read 1 chapter, now I need to read 2 chapters. If I write a half-page essay for a class, now I must be able to write a page. So now you see, more effort needs to be put in for the daily learning activities. This is mean extra time for learning. If I sit down to read at 9 pm (after isya'), now I need to sit down and read right after dinner, around 7.30 pm (after maghrib). So time for learning has to change as there will be more activities to cover. The more the learning that needs to get done for the day, the more time I needed to assign for learning that day. That means time management. It means I need to readjust my schedule for play and learn. I cannot play all the time and have very little time for learning. I cannot learn all the time and have no time to play. So what did I do? I did all my homework and reading daily and finished them daily, before I go to bed. I play only when I have completed my learning or studies. I pushed 'play' to weekends. I learned most of the time during the week because I wasn't going to learn on weekends as they were meant for 'play' (relaxation). So I read on weekdays and played the piano, washed the clothes, went shopping, went strolling and picnic on weekends. I also change my revision for exams. I started revising after each class lecture or practical. I made sure I understood texts, diagrams and pictures. Because there were so many images as I was doing double major and three minors, I had to learn how to 'store' things in my brain. So I took up speed reading and learned photographic memory. If you are a keen Quran reader, speed reading is easy. If you're not a good Quran reader, speed reading is not for you. Go reverse and learn Quran reading first because that helps speed reading. When you can read fast, the brain works fast. When the brain works fast, it is both active and receptive. When the brain is in this 'activated state', it takes care of everything it wants to and shifts gears automatically. How to get the brain to that state? Sufficient rest, lots of fresh air, clean environment, conducive environment, relaxing atmosphere, good surroundings, not noisy not too quiet, good seasons - not extreme, lots of good food. I lived in the hostel and had a very good environment and good food. So I was making great changes in no time. For languages, I sat in front of the TV and learned US English. By 6 months I was proficient and a fluent speaker. I put English to practice so I wouldn't lose it rapidly because any language acquired goes away fast without practice. So I was really doing a lot of good changes for myself. I never felt sorry nor tired of making small changes whenever the opportunity arises. I wrote down words which I didn't know and looked them up in dictionaries - we didn't have Internet or smartphones back then.

How to Know if the Changes are OK
Very simple, my grades went up. Soon, I was near the top of my class. By second, third and final year, I was at the top pf my class. I stayed as top student and my grades never ever fell. So I was progressing ok. I enjoyed doing things my way and nobody said No or anything bad that would hurt me. So I was a happy kid doing things my own way. I had created in myself a means to direct my own learning style and I was comfortable with my learning and my grades were good. I enjoyed every bit of my university life because learning was so enjoyable. I was always looking forward to class. I didn't want to miss class. I wanted be present in all my classes and be able to be in class before my professors arrived and spoke to the class. I wanted to hear their first words and how they addressed students. I wanted to be very knowledgeable like my professors. I admired them for their simplicity, generosity and knowledge. I didn't want anything else. I just wanted to be as smart as my professors. So I watched and observed each one of my professors. Everyone left me a deep impression. The overall impact of that is to have very goof will power to succeed, and succeed I did. Alahmdulillah.

Being Top Student
It feels really great being a top student. It feels good, really good being that most coveted seat - TOP STUDENT! Who wouldn't want to be a top student?! So I was a top student and my professors admired me for being that as they labeled me as GENIUS!!!!!  Goodness Gracious! Alhamdulillah. Now, with that kind on admiration from my own professors, I had nothing to lose but to strive on and maintain my status as TOP STUDENT. It was easy because I had mastered the means of becoming a top student and I was comfortable. I didn't become obsessed, I just enjoying learning and learning new things. I could understand things easily and nothing was too difficult. If I didn't understand I could just stop my professor and ask. I wasn't shy at all since my English was ok after 4 years in undergraduate university and 6 years at my postgraduate university. Nobody could tell I am Malaysian. People thought I was Hispanic or Chicano but I spoke really good California English for a Malaysian teenager and youth. So I really enjoyed myself with my newly acquired soft skills and learning methodology.

Is being Top Student any good?
I think there is more good as a top student. I get to speak in class and I get to head my class discussion. I read widely so I had a lot of facts and factual recall is easy with practice. So being top student is really worth it. I totally enjoyed it, unlimited.

Take home message
Learn to me a good student first, make small changes until the changes come naturally. Improve on English language so it doesn't become an obstacle. That's it! InsyaAllah, it will work for you too.

Take care!

Study hard but study smart. Aim to be a top student. Come what may, stay as top student. Always and all ways.

Making it to Medical School

Many students wrote in to find out but I am not the right person to answer doubts and queries. Students and parents should write directly to the deans of the medical schools whether in Malaysia or overseas. If scholarship is a concern, parents/students can apply for PTPTN or MARA/JPA scholarships.

There are so many medical schools to choose from. Once students register they cannot simply hop from one school to another as there are many obstacles.

Where do you start searching for medical schools? It depends. If the student is from a poor family, I would suggest to seek advice directly from the dean of any public university that has a medical school. In my last care of students' database, I found that 60% of our local students were from poor families. In some families, the father had died and the mother had to work to earn an income to feed the family. Some of these jobs were harsh, like driving a school bus/van. Many poor students had trouble going home as they did not have money. But our medical school had set up a students' fund to assist these poor students during crisis.

Students usually score 4.0 (four flat) before applying to medical school. But nowadays, many medical schools have programs and remedies to help non 4-flat students once they register. Many medical schools today will accept students who are motivated, have passion, and are willing to give their all to study hard and obtain a medical degree. This gives hope to students and parents to approach the various medical school with an open heart, and try and ask around for seat in medical school.

Which are the good medical schools to try? This is my personal list and views:

1. USM medical school - limited to 180 students per year. Space is a major constraint. We don't have good facilities and we are already 30 years old. Only BPSP is new. We don't have corpses at all, so Anatomy is dry.
2. UniKL medical school in Ipoh - the Anatomy Dept is very good as they have corpses and the lecturers (all Burmese) are very dedicated. Their OSPE (exam) is also very good and well set-up. The MCQ format is different from that of USM medical school.
3. Cyberjaya Medical University - the lecturers are very good and students successfully complete their degrees. Students can transfer credits here and complete a medical degree.
4. Management & Science University (MSU) in Shah Alam - the medical program is 1 year in Shah Alam and 5 years overseas  in Bangalore. Students seem to enjoy the extra coaching and intensive teaching-learning activities, and good weather in Bangalore. The housing, teaching & learning facilities in Bangalore are modern and better than in Malaysia. 
5. USM KLE medical program in Belgaum, India - same program as USM but there is good coaching by the dedicated teachers. The place is new. Facilities are modern and better than in USM and elsewhere in Malaysia.
6. College Insaniah in Alor Star, Kedah - the program is good but sometimes they have problems as aired on TV and news recently.

A traditional Malay remedy for small gallstones

Caution:
This traditional remedy may ONLY work if your gallstone(s) is really SMALL (like a grain of rice) as detected by ultrasound of the abdomen. This traditional remedy will NOT EVER work on gallstones that are already large, as large as your thumb (1-2 cm long)! Only surgery to remove the entire gallbladder will help in advanced cases where the large gallstones are a cause of worry and colic as the gallstone(s) try to exit the gallbladder.

How do you dissolve gallstones (batu karang hempedu)?

This may work for some, and not work for others. For many whom this remedy has worked, they shared the formula with friends and now the formula has reached me. So I will share with you.

What you will need:

Take 33 pieces of belalai gajah leaves and 33 pieces of lidah jin leaves and 1-2 Granny Smith (green) apples. 

What to do?

Wash and place the leaves in a blender. Chop the green apples (with seeds) and add to blender. Add cold water (from the fridge). Blend till fine. It will fizzle at the top. Strain into drinking cups - the thicker the better taste. Add 1-2 plastic teaspoonful honey - the sweeter the better. Stir and drink cold, immediately. The drink is light green when freshly prepared, sweet and smells of green apples. If you let is stand long enough, it turns an ugly wooden color, but can still be taken.

What else is this remedy good for?

This same remedy works for those with diabetes and renal problems (renal stones/batu karang kencing). Can take it daily. I take it for buka puasa. I take 2 cups full and I feel ok. This is much better than commercial apple juice or fresh apple juice.

Lidah jin or Strobilanthes crispus.
Other known names: Pecah kaca, Pecah beling, Bayam karang, Keji beling, Panglima hitam, and Black-face general. 

Belalai gajah or Clinacanthus nutans.
Other known names: Dandang gendis, Daun kalingsir, Sabah snake grass, Drooping Clinacanthus, Phaya-Yor, and Snake Plant.

Add to blender

Juice for dissolving gallstones

Scientific names of the 2 plants as provided by the Medicinal Plants Interest Group in Facebook:

https://www.facebook.com/groups/100705113390880/

Ahmad Fuad Haji Morad: The "Lidah Jin", or rather the correct vernacular name, "Jin batu" (referring to its ability to act upon gallstones) is Strobilanthes crispus. Other names mentioned are - Pecah kaca, Pecah beling, Bayam karang, Keji beling, Panglima hitam, Black-face general. Whilst, the one labeled "Belalai gajah" is Clinacanthus nutans. Other names used for the species are - Dandang gendis, Daun kalingsir, Sabah snake grass, Drooping Clinacanthus, Phaya-Yor, Snake Plant. Both are in the same plant family, Acanthaceae.

External link:
http://www.healthline.com/health/gallstones#Overview1

Serotonin

Diet
Both serotonin and its precursor tryptophan are amino acids. Our diet cannot feed our brain the serotonin it needs because the blood-brain barrier (BBB) will block it from entering. Even tryptophan cannot cross BBB. Low serotonin is linked with depression.
http://bebrainfit.com/serotonin-foods-mood-brain/


Sources

1. Serotonin is released into the space between neurons, and diffuses over a relatively wide gap (>20 µm) to activate 5-HT receptors located on the dendrites, cell bodies and presynaptic terminals of adjacent neurons.
2. Serotonin in mammals is made by two different tryptophan hydroxylases: TPH1 produces serotonin in the pineal gland and the enterochromaffin cells, while TPH2 produces it in the raphe nuclei and in the myenteric plexus. 
3. Genetically altered mice lacking TPH1 develop progressive loss of heart strength early on. They have pale skin and breathing difficulties, are easily tired, and eventually die of heart failure. Genetically altered mice that lack TPH2 are normal when they are born. However, after three days, they appear to be smaller and weaker, and have softer skin than their siblings. In a purebred strain, 50% of the mutants died during the first four weeks, but in a mixed strain, 90% survived. Normally, the mother weans the litter after three weeks, but the mutant animals needed five weeks. After that, they caught up in growth and had normal mortality rates. Subtle changes in the autonomic nervous system are present, but the most obvious difference from normal mice is the increased aggressiveness and impairment in maternal care of young. Despite the blood–brain barrier, the loss of serotonin production in the brain is partially compensated by intestinal serotonin. The behavioural changes become greatly enhanced if one crosses TPH1- with TPH2-lacking mice and gets animals that lack TPH entirely.
4. Serotonin secreted from the enterochromaffin cells eventually finds its way out of tissues into the blood. There, it is actively taken up by blood platelets, which store it. When the platelets bind to a clot, they disgorge serotonin, where it serves as a vasoconstrictor and helps to regulate hemostasis and blood clotting. 
5. Serotonin also is a growth factor for some types of cells, which may give it a role in wound healing.
6. Approximately 90% of the human body's total serotonin is located in the enterochromaffin cells in the alimentary canal (gut), where it is used to regulate intestinal movements. 
7. The remainder is synthesized in serotonergic neurons of the CNS, where it has various functions. These include the regulation of mood, appetite, and sleep. 
8. Modulation of serotonin at synapses is thought to be a major action of several classes of pharmacological antidepressants.

Actions

1. Serotonin is known to regulate aging, learning and memory. 
2. Serotonin also has some cognitive functions, including memory and learning. 
3. Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS) of animals and humans. It is popularly thought to be a contributor to feelings of well-being and happiness.
4. In humans, serotonin levels are affected by diet. An increase in the ratio of tryptophan to phenylalanine and leucine will increase serotonin levels. Fruits with a good ratio include dates, papayas and bananas. Research also suggests eating a diet rich in carbohydrates and low in protein will increase serotonin by secreting insulin, which helps in amino acid competition. However, increasing insulin for a long period may trigger the onset of insulin resistance, obesity, type 2 diabetes, and lower serotonin levels. Muscles use many of the amino acids except tryptophan, allowing more muscular individuals to produce more serotonin.
5. Serotonin functions as a neurotransmitter in the nervous systems of simple, as well as complex, animals.
6. Serotonin is a neurotransmitter and is found in all bilateral animals, where it mediates gut movements and the animals' perceptions of resource availability. 
7. Serotonin is found in animals, fungi and plants. Serotonin is present in insect venoms and plant spines and serves to cause pain, which is a side effect of serotonin injection. 
8. Serotonin is produced by pathogenic amoebae, and its effect on the gut causes diarrhea. 
9. Its widespread presence in many seeds and fruits may serve to stimulate the digestive tract into expelling the seeds.
10. Serotonin is mainly metabolized to 5-HIAA, chiefly by the liver. Metabolism involves first oxidation by monoamine oxidase to the corresponding aldehyde. This is followed by oxidation by aldehyde dehydrogenase to 5-HIAA, the indole acetic acid derivative. The latter is then excreted by the kidneys. 
11. One type of tumor, called carcinoid, sometimes secretes large amounts of serotonin into the blood, which causes various forms of the carcinoid syndrome of flushing, diarrhea, and heart problems. 
12. Because of serotonin's growth-promoting effect on cardiac myocytes, persons with serotonin-secreting carcinoid may suffer a right heart (tricuspid) valve disease syndrome, caused by proliferation of myocytes onto the valve.
13. Since serotonin is an indicator of bleeding, a sudden large increase in peripheral levels causes pain. The reason wasps and deathstalker scorpions have serotonin in their venom may be to increase the pain of their stings on large animals, and also to cause lethal vasoconstriction in smaller prey.
14. Some serotonergic agonist drugs also cause fibrosis anywhere in the body, particularly the syndrome of retroperitoneal fibrosis, as well as cardiac valve fibrosis. In the past, three groups of serotonergic drugs have been epidemiologically linked with these syndromes. They are the serotonergic vasoconstrictive antimigraine drugs (ergotamine and methysergide), the serotonergic appetite suppressant drugs (fenfluramine, chlorphentermine, and aminorex), and certain anti-Parkinsonian dopaminergic agonists, which also stimulate serotonergic 5-HT2B receptors. 
15. Serotonin, in addition, evokes endothelial nitric oxide synthase activation and stimulates, through a 5-HT1B receptor-mediated mechanism, the phosphorylation of p44/p42 mitogen-activated protein kinase activation in bovine aortic endothelial cell cultures. 
16. In blood, serotonin is collected from plasma by platelets, which store it. It is thus active wherever platelets bind in damaged tissue, as a vasoconstrictor to stop bleeding, and also as a fibrocyte mitotic (growth factor), to aid healing.
17. In humans, though insulin regulates blood sugar and IGF regulates growth, serotonin controls the release of both hormones, so serotonin suppresses insulin release from the beta-cells in the pancreas, and exposure to SSRIs reduces fetal growth. 
18. Human serotonin can also act as a growth factor directly. Liver damage increases cellular expression of 5-HT2A and 5-HT2B receptors. Serotonin present in the blood then stimulates cellular growth to repair liver damage. 5HT2B receptors also activate osteocytes, which build up bone. However, serotonin also inhibits osteoblasts, through 5-HT1B receptors.
19. In humans, increased blood serotonin levels have been shown to be significant negative predictor of low bone density. Serotonin can also be synthesized, albeit at very low levels, in the bone cells. It mediates its actions on bone cells using three different receptors. Through Htr1b receptors, it negatively regulates bone mass, while it does so positively through Htr2b and Htr2c. There is very delicate balance between physiological role of gut serotonin and its pathology. Increase in the extracellular content of serotonin results in a complex relay of signals in the osteoblasts culminating in FoxO1/ Creb and ATF4 dependent transcriptional events.
20. These studies have opened a new area of research in bone metabolism that can be potentially harnessed to treat bone mass disorders.
21. In humans, defective signaling of serotonin in the brain may be the root cause of sudden infant death syndrome (SIDS). 
22. Scientists from the European Molecular Biology Laboratory in Monterotondo, Italy genetically modified lab mice to produce low levels of the neurotransmitter serotonin. The results showed the mice suffered drops in heart rate and other symptoms of SIDS, and many of the animals died at an early age. Researchers now believe low levels of serotonin in the animals' brainstems, which control heartbeat and breathing, may have caused sudden death, they said in the July 4, 2008 issue of Science.
23. If neurons that make serotonin — serotonergic neurons — are abnormal in infants, there is a risk of sudden infant death syndrome (SIDS).
24. Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system, because it does not cross the blood–brain barrier (BBB). However, tryptophan and its metabolite 5-hydroxytryptophan (5-HTP), from which serotonin is synthesized, can and do cross the BBB. These agents are available as dietary supplements, and may be effective serotonergic agents. 
25. One product of serotonin breakdown is 5-hydroxyindoleacetic acid (5-HIAA), which is excreted in the urine. 
26. Serotonin and 5-HIAA are sometimes produced in excess amounts by certain tumors or cancers, and levels of these substances may be measured in the urine to test for these tumors.
27. In animals and humans, serotonin is synthesized from the amino acid L-tryptophan by a short metabolic pathway consisting of two enzymes: tryptophan hydroxylase (TPH) and amino acid decarboxylase (DDC). The TPH-mediated reaction is the rate-limiting step in the pathway. TPH has been shown to exist in two forms: TPH1, found in several tissues, and TPH2, which is a neuron-specific isoform.
28. Serotonin can also signal through a nonreceptor mechanism called serotonylation, in which serotonin modifies proteins. This process underlies serotonin effects upon platelet-forming cells (thrombocytes) in which it links to the modification of signaling enzymes called GTPases that then trigger the release of vesicle contents by exocytosis. A similar process underlies the pancreatic release of insulin. 
29. The effects of serotonin upon vascular smooth muscle tone (this is the biological function from which serotonin originally got its name) depend upon the serotonylation of proteins involved in the contractile apparatus of muscle cells.
30. Serotonergic action is terminated primarily via uptake of 5-HT from the synapse. This is accomplished through the specific monoamine transporter for 5-HT, SERT, on the presynaptic neuron. 
31. Various agents can inhibit 5-HT reuptake, including MDMA (ecstasy), amphetamine, cocaine, dextromethorphan (an antitussive), tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). 
32. Interestingly, a 2006 study conducted by the University of Washington suggested a newly discovered monoamine transporter, known as PMAT, may account for "a significant percentage of 5-HT clearance". 
33. Contrasting with the high-affinity SERT, the PMAT has been identified as a low-affinity transporter, with an apparent Km of 114 micromoles/l for serotonin; approximately 230 times higher than that of SERT. 
34. However, the PMAT, despite its relatively low serotonergic affinity, has a considerably higher transport 'capacity' than SERT, "... resulting in roughly comparable uptake efficiencies to SERT in heterologous expression systems." 
35. The study also suggests some SSRIs, such as fluoxetine and sertraline, inhibit PMAT but at IC50 values which surpass the therapeutic plasma concentrations by up to four orders of magnitude; therefore, SSRI monotherapy is "ineffective" in PMAT inhibition. 
36. At present, no known pharmaceuticals are known to appreciably inhibit PMAT at normal therapeutic doses. The PMAT also suggestively transports dopamine and norepinephrine, albeit at Km values even higher than that of 5-HT (330–15,000 μmoles/L).
37. The 5-HT receptors, the receptors for serotonin, are located on the cell membrane of nerve cells and other cell types in animals, and mediate the effects of serotonin as the endogenous ligand and of a broad range of pharmaceutical and hallucinogenic drugs. 
38. With the exception of the 5-HT3 receptor, a ligand-gated ion channel, all other 5-HT receptors are G protein-coupled, seven transmembrane (or heptahelical) receptors that activate an intracellular second messenger cascade.
39. Several classes of drugs target the 5-HT system, including some antidepressants, antipsychotics, anxiolytics, antiemetics, and antimigraine drugs, as well as the psychedelic drugs and empathogens.
40. The psychedelic drugs psilocin/psilocybin, DMT, mescaline, and LSD are agonists, primarily at 5HT2A/2C receptors. The empathogen-entactogen MDMA releases serotonin from synaptic vesicles of neurons.
41. Drugs which alter serotonin levels are used in depression, generalized anxiety disorder and social phobia. 
42. Monoamine oxidase inhibitors (MAOIs) prevent the breakdown of monoamine neurotransmitters (including serotonin), and therefore increase concentrations of the neurotransmitter in the brain. 
43. MAOI therapy is associated with many adverse drug reactions, and patients are at risk of hypertensive emergency triggered by foods with high tyramine content, and certain drugs. 
44. Some drugs inhibit the reuptake of serotonin, making it stay in the synaptic cleft longer. 
45. The tricyclic antidepressants (TCAs) inhibit the reuptake of both serotonin and norepinephrine. 
46. The newer selective serotonin reuptake inhibitors (SSRIs) have fewer side effects and fewer interactions with other drugs.

http://upload.wikimedia.org/wikipedia/commons/1/1c/Serotonin_biosynthesis.svg
http://upload.wikimedia.org/wikipedia/en/8/88/Dopamineseratonin.png
http://en.wikipedia.org/wiki/Serotonin

Epinephrine (Adrenaline)

1. Lipid mobilization.
2. Glycogenolysis is stimulated by epinephrine and/or norepinephrine.
3. Epinephrine (or adrenaline or adrenalin) is a hormone and a neurotransmitter. 
4. Epinephrine has many functions in the body: regulating heart rate, blood vessel and air passage diameters, and metabolic shifts. 
5. Epinephrine release is a crucial component of the fight-or-flight response of the sympathetic nervous system. 
6. Epinephrine is one of a group of monoamines called the catecholamines. 
7. Adrenaline is used to treat a number of conditions including: cardiac arrest, anaphylaxis, and superficial bleeding. 
8. It has been used historically for bronchospasm and hypoglycemia. 
9. Newer treatments for bronchospasm and hypoglycaemia, such as salbutamol, a synthetic epinephrine derivative, and dextrose, respectively, are currently preferred.
10. Adrenaline is also used as a bronchodilator for asthma if specific β2 agonists are unavailable or ineffective.
11. Adrenaline is used as a drug to treat cardiac arrest and other cardiac dysrhythmias resulting in diminished or absent cardiac output. Its actions are to increase peripheral resistance via α1receptor-dependent vasoconstriction and to increase cardiac output via its binding to β1 receptors.
12. Due to its vasoconstrictive effects, adrenaline is the drug of choice for treating anaphylaxis. Allergy patients undergoing immunotherapy may receive an adrenaline rinse before the allergen extract is administered, thus reducing the immune response to the administered allergen.
13. Adrenaline is added to injectable forms of a number of local anesthetics, such as bupivacaine and lidocaine, as a vasoconstrictor to slow the absorption and, therefore, prolong the action of the anesthetic agent. Due to epinephrine's vasoconstricting abilities, the use of epinephrine in localized anesthetics also helps to diminish the total blood loss the patient sustains during minor surgical procedures.

http://en.wikipedia.org/wiki/Epinephrine

Injectable epinephrine:
http://en.wikipedia.org/wiki/File:Adrenalin_Ampulle.jpg

Catecholamines:
http://en.wikipedia.org/wiki/Catecholamine

Cortisol

CORTISOL

Synonyms

Cortisol (11 b,17,21, trihydroxy-4-pregnene-3,20-dione) (in humans), natural form

Hydrocortisone, this form is prescribed by doctors

Corticosterone (11 b,21,d,hydroxypregn-4-ene-3,20-dione) (in rodents), synthetic form

Cortisol is a stress hormone. It is a steroid hormone, more specifically a glucocorticoid. 

Structure of cortisol

Cortisol is the major natural glucocorticoid. Semisynthetic derivatives with greater hormonal activity than that of cortisol are dexamethasone, prednisone, and triamcinolone

Structure of steroid hormones.

From http://what-when-how.com/molecular-biology/glucocorticoids-molecular-biology/

Production of cortisol

Glucocorticoid secretion is enhanced during stress conditions, such as anxiety, hunger, and trauma.

1. Cortisol is a stress hormone as well as a steroid hormone, and more specifically a glucocorticoid. 
2. It is released in response to stress and a low level of blood glucocorticoids. 

Regulation of cortisol production

The synthesis of glucocorticoids in the zona fasciculata of the adrenal cortex (in the adrenal gland) and their release into the blood circulation is regulated by adrenocorticotropic hormone (ACTH). 

ACTH is produced in the anterior lobe of the hypophysis, in response to stimuli coming either from the neuroendocrine cells of the paraventricular nuclei of the hypothalamus (corticotropin releasing hormone, CRH) or from the periphery (blood cortisol concentration).

High blood cortisol levels reduce (by feedback inhibition) the production of both CRH and ACTH. This regulatory circuit is called the hypothalamus-pituitary-adrenal axis

Regulation of cortisol production by the hypothalamus-pituitary-adrenal axis. 

From http://what-when-how.com/molecular-biology/glucocorticoids-molecular-biology/

Why do we need cortisol?

1. It is the most important human glucocorticoid. 
2. It is essential for life.
3. It regulates or supports a variety of important cardiovascular, metabolic, immunologic, and homeostatic functions.
4. Various synthetic forms of cortisol are used to treat a variety of diseases, eg, hydrocortisone.

Functions of cortisol

1. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat, protein and carbohydrate metabolism.
2. It also decreases bone formation. 
3. Cortisol counteracts insulin, contributes to hyperglycemia-causing hepatic gluconeogenesis, and inhibits the peripheral utilization of glucose (insulin resistance) by decreasing the translocation of glucose transporters (especially GLUT4) to the cell membrane. 
4. Cortisol increases glycogen synthesis (glycogenesis) in the liver. The permissive effect of cortisol on insulin action in liver glycogenesis is observed in hepatocyte culture in the laboratory, although the mechanism for this is unknown.

External Links
http://en.wikipedia.org/wiki/Cortisol
http://www.netterimages.com/image/9025.htm

What-When-How
http://what-when-how.com/molecular-biology/glucocorticoids-molecular-biology/

Cortisol for injection
http://upload.wikimedia.org/wikipedia/commons/d/d6/Cortisol_for_injection.jpg

PowerPoints

http://slideplayer.com/search/cortisol/

http://slideplayer.com/slide/3469175/#

http://slideplayer.com/slide/3883704/#

http://slideplayer.com/slide/4404396/#

Steroidogenesis

http://upload.wikimedia.org/wikipedia/commons/1/13/Steroidogenesis.svg

Lipid Metabolism

SEQ: Describe lipid metabolism under fasting state. (10 marks)

MODEL ANSWER:

No.	Details	Marks
1.	During fasting, there are many changes in the body and blood in the following: i.      nutrient storage, supply and levels; ii.     hormone secretions and levels; iii.    blood pH; iv.    Usage of alternative energy resources v.     energy storage, supply and levels;	2
2.	Order of usage of energy resources within the body: i.      Glucose (0-4 hrs), ii.     Glycogen (during sleep), iii.    Proteins (by day 3), and iv.    Lipids (from day 3 onward) v.     Ketones	2
3.	Chemical processes & pathways (catabolism): a.     glycolysis, b.    proteolysis, c.     lipolysis, d.    glycogenolysis, e.     b-oxidation f.     TCA cycle g.    ETC	2
4.	Lipid metabolism in fasting: i.      Hyperglycaemic hormones: Increase ii.     Insulin: Decrease iii.    Exogenous lipoprotein metabolism: No iv.    Endogenous lipoprotein metabolism: Yes v.     Fat mobilization (from adipose tissue): Active vi.    Carnitine shuttle: Active vii.   b-oxidation: Very active viii.  TCA cycle: Active ix.    ETC: Active x.     Ketogenesis: Very active xi.    Ketolysis: Active xii.   Gluconeogenesis (from glycerol): Yes	2
5.	Effects of lipid metabolism during fasting (fasting lipid profile): i.      Blood glucose: low-normal ii.     Blood free fatty acids (FFA): high iii.    Blood ketones: high, acidic --> ketoacidosis iv.    Blood pH: metabolic acidosis, due to high ketones v.     Blood amino acids: low vi.    Blood glycogen: nil	2

STUDENTS' PROBLEMS WITH THIS QUESTION

Wrong answers

Lipid Digestion

Exogenous Lipoprotein Metabolism (Chylomicron metabolism)

Exogenous + Endogenous Lipoprotein Metabolism (CM + VLDL metabolism)

Lipid Digestion: Dietary fat will be combined with bile salt and formed into the water soluble micelles. Then, micelles will be transported to the intestinal absorption site. Once the micelles already absorbed across the intestinal mucosal cell, dietary fat will be reesterified to form into the triglyceride and also cholesterol esters and travels in the blood plasma.

Exogenous Lipoprotein Metabolism: Chylomicron will be released into the blood circulation by travels in lymphatic duct and thoracic duct. Chylomicron will be hydrolysed by the enzyme lipoprotein lipase (LPL) to become monoglyceride, diglyceride and free fatty acid to be uptake by the cells. While chylomicron remnant be uptake by the liver to undergo delipidation to be used to synthesize new lipoprotein and building of plasma membrane.

Gluconeogenesis: Under fasting state, lipid undergo gluconeogenesis to supply glucose. b-oxidation of lipid produce acetyl CoA. Under fasting state, lipid undergo lipolysis, and FFA undergo b-oxidation. Lipid is first breakdown and transfer into mitochondria matrix to form oxaloacetate (OAA). OAA convert to citrate and transported into cytosol. In cytosol, OAA is converted back by citrate. Citrate convert into phosphoenolpyruvate (PEP) by PEP carboxykinase. PEP is converted into fructose-1,6-biphosphate by fructose-1,6-biphosphatase. Fructose-1,6-biphosphate dephosphorylate bt fructose-6-phosphatase into fructose-6-phosphate. Frutose-6-phosphate convert into glucose-6-phosphate by phosphoglucomutase. Glucose-6-phosphate dephosphorylated into glucose by glucose-6-synthase. Glucose enter glycolysis to supply energy.

When fasting, glucose stores are depleted. Other sources of energy are needed by the body such as protein, fatty acids, and ketone bodies. Gluconeogenesis, glycogenolysis are all in the action at higher levels. Glucagon stimulate the secretion of fatty acid lipase to degrade fatty acid. This is termed lipolysis. This leads to increase in free fatty acids, that is degraded  to lactic acid and used in gluconeogenesis for ketone body generation. Ketone bodies are alkaline in nature and this leads to ketoalkalosis. Gluconeogenesis takes place 90% in the liver and 10% in the kidney. Lipolysis increase which leads to increase blood fatty acid and form alkaline urine.

Ambiguous answers

Fatty acyl-CoA will undergo gluconeogenesis to produce glucose.

Gluconeogenesis is process to produce glucose from non carbohydrate molecules.

During fasting, glucose will be breakdown first followed up by lipid breakdown, then only goes to protein breakdown.

Meaningless answers

Lipid –[fasting]--> FA + Glycogen (should be Glycerol)

Lipid will undergo gluconeogenesis

Lipid is hydrolysed to acetyl CoA

Fatty acids with short chain is transported directly into the blood circulation where it binds to ammonia and is stored as triglycerides.

Fatty acids with long chain and glycerol absorbed into the lacteal, then flows into the thoracic duct and finally into the blood.

Fatty acids is added with vitamen A, D, E and K to produce chylomicrons.

The chylomicrons are broken down into fatty acid and glycerol.

Remnents of the chylomicrons are stored in the liver.

Glucose will undergo glycolysis to produce high energy which is ATP.

b-oxidation itself can produce ATP.

Breakdown on lipid into fatty acid and triglycerides.

Lipid ---> FFA  +  TG [this is wrong] vs. Lipid ---> FFA  + Glycerol [this is correct]