Friday, April 04, 2014

The taste of Water .

The Taste of Water . 


Andre Willers 
4 Apr 2014 
Synopsis :
Water tastes slightly sweetish .
 
Discussion :
1.How to taste water .
   1.1Cleanse the taste receptors (palate)
   1.2Crush a very thin slice of garlic in about 50 ml of water .
   1.3Rinse the mouth and gargle about 3 times . Spit it out .
   1.4 Now , taste the water .
 
2. What is going on ?
The allicin in crushed garlic is an extremely powerful anti-bacterial agent .
See Appendix B .
Bacteria in the mouth have evolved to explosively increase when nutrients become available .
They compete for access to the positive-feedback taste receptors on the tongue (ie sweetness)
Allicin (weak garlic) clears this .
 
3.Try it .
A sugary water tastes significantly less sweet if mixed with a weak garlic solution .

4. Training the Gluco-systems (Diabetes II)
A thin sliver of Garlic crushed in 50 ml of water , then mixed with about 1-2 gm(1/5 tsp)  sugar  . Stir .Rinse mouth and swallow .
This interrupts the sugar preparation pathway between the mouth and the descending duodenum .
See Appendix C
 
5. Garlic chewing gum .
Not garlic flavoured . The chewing hum must contain the capsules of aliin and aliinase to produce allicin when chewed .
Make your own by inserting thin slivers of garlic cloves into chewing gum . Do not use sugar free chewing gum .
 
6. Interesting side effects .
Good foods will taste better , and bad foods will taste terrible .
 
7. The human sense of smell will also sharpen considerably .
The latest research indicates that the human sense of smell is considerably better (factor of 100)  than the present perception .
 
8. Active perfumes :
Microspores of perfume ingredients , which , when mixed releases a resultant perfume can be sprayed or rolled on areas like armpits or thighs  where crushing takes place .
 
Sweet dreams
 
Regards
 
Andre
 
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Appendix A
Ask Anything: What Does Water Taste Like?
H2-oh-so-tasty
By
Posted 01.29.2014 at 2:16 pm


Momoko Takeda/Getty Images
For thousands of years, philosophers claimed that water had no flavor. It’s the baseline for the sense of taste, they said—a starting point and null condition. What water is to tongues, darkness is to eyes and silence is to ears. “The natural substance water per se tends to be tasteless,” wrote Aristotle. In his view, it serves only as the vehicle for flavor.
But eventually, scientists began to notice that a draught of pure distilled water could provoke a certain taste. Some found it bitter on the tongue; others said it was insipid. By the 1920s, evidence was mounting that water changes flavor depending on what you happen to have tasted just before. Take a sip of Poland Spring after putting something acidic on your tongue, and it may taste a little sweet. Drink some after eating salt, and it could have a hint of bitterness.
In the 1960s and 1970s, Yale psychologist Linda Bartoshuk published a series of papers on the so-called aftertastes of water. When a person eats or drinks, his or her taste cells become adapted to that stimulus, Bartoshuk explained. If you then wash out that flavor with water, the cells rebound into an active state. It’s something like the after-image of a color seen against a sheet of blank white paper.
You don’t even need to eat or drink to experience the same effect. Bartoshuk found that a person’s own saliva can spruce up the taste of water. As you go about your day, your tongue will be awash with slightly salty spit. The saliva doesn’t taste like anything because your mouth has become habituated to it. But rinse the spit away with water and your cells will rebound to a bitter or sour taste with your next sip.
Among physiologists, that’s been the dogma for more than 30 years: Water has a flavor but only as an aftereffect of tasting other things. In recent years, however, a small group of scientists have argued that water can be sensed even on its own. Starting in the early 2000s, researchers published data showing that certain parts of the brain—in both humans and laboratory rats—respond specifically to water. At around the same time, a group at the University of Utah found that mammalian taste cells make proteins called aquaporins, which serve to channel water through cell membranes. The aquaporins, which are common in other types of cells, provide a possible way for water to stimulate taste cells directly.
If water has a special taste for rats and people, it wouldn’t be unprecedented in the animal kingdom. It’s long been known that insects have a taste for water. Scientists have proved that fruit flies taste chemicals through bristles that protrude from their wings, legs, and proboscis. The bristles connect to a set of neurons tuned to sugary and bitter tastes, along with changes in osmotic pressure.
Even so, most neuroscientists doubt that such a mechanism exists in mammals too. “You will find a lot of people who don’t believe that water has a taste, period,” says Patricia Di Lorenzo of Binghamton University. Her laboratory has identified neurons  that respond only to water in the brain stem of a rat at several points along the pathway used to process taste, but she’s gotten little support for this idea among her colleagues. “I’m out of the water business,” she admits. “When you’re in a field where nobody believes what you say, then you move on.”
Sidney Simon, a physiologist at Duke University, describes a similar experience. He found water-specific cells in the rat’s gustatory cortex. “There’s a good possibility that there’s a water response in mammals,” he says. “It’s not a QED—it’s suggestive.” But other groups haven’t found the same. That could be because they’re only using anesthetized animals, Simon says, and testing their responses only at the front of the tongue. To find the cells that taste water, you may have to look toward the back of the mouth. In any case, it makes perfect sense to him that water should have its own taste. “It’s the most common thing in the world,” he says. “It’s 75 percent of your body. It’s 75 percent of the planet. I mean, why wouldn’t you develop something like that?”
This article originally appeared in the February 2014 issue of Popular Science.
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Appendix B

http:/ Sunday, April 10, 2011

Garlic and the Plant-Herbivore Wars .
Andre Willers
10 Apr 2011

Synopsis:
Garlic (Allicin) is a toxin produced by binary components alliin and enzyme alliinase These are kept in separate pockets , but mix when the plant is damaged (eaten) , producing allicin .

Dicussion :
This is a very old and beautiful mechanism , verging on symbiosis .

Note the presence of Sulfur : it evolved pre-oxygen , and evolved to keep pace .
It originally evolved to zap viruses and other bacteria to give the originators a relative advantage .
In multicellular organisms , it does the same .
Notice that the chemical (Allicin) evolved first , then reversed into the genomes of various organisms because it was so useful .
Allicin remains invariant , and genomes adapt to it .
A sort of "Inverse Prion"

But it is kept in check by various mechanisms :

1.Bad taste and smell and a burning sensation

This limits eating . The burning is sensation is caused by the activation of a separate neural network that evolved to simulate a burning sensation . This evolved into capsaicum receptors in mammals . Birds , reptiles and dinosaurs had equivalents .
Note sensitivity of marine mollusks to anti-fouling paints based on capsaicum-like chemicals .

2.Deactivation of enzyme alliinase if ph<3 br=""> This led to gastric acids .
Symbiotic bacteria in the intestines must be kept protected .
Swallowing garlic plants or powders will not work
If you drink coke ,pepsi etc , with your garlic , there will be little health benefit (see Appendix A for acidity of popular drinks)
But too much of a good thing can harm . A swig of acid drink(ph<3 .="" 2="" after="" at="" bacterial="" be="" br="" but="" eating="" garlic="" intervals="" it="" minute="" must="" oral="" pulsed="" reset="" systems="" will="">
3.Quick breakdown of allicin at body temperatures :

16 hours at 23 C (from Wiki)

64 hours at 3 C (the fridge) . Throw away supermarket or even frozen minced garlic as far as health effects are concerned .

5.7 hours at 38 C (doubling of chemical activity every 10 C)
Very little allicin makes it through to the small intestines to upset the gut flora .

Cooking :
5 minutes at 100 C . (doubling of chemical activity every 10 C)
There is very little allicin left after 5 minutes of cooking .

The effects of Allicin is then concentrated in the mouth and throat : where the rubber hits the tar . Where any bacteria is an enemy . Kill them all , and let the immune system sort out the remainder .
This works well in pulsed dosages , hence another reason for the rapid breakdown of allicin .

4.Breakdown accellarators :
There is some evidence that there are some other chemicals in garlic that speeds up breakdown of allicin . Presumably binary , as well .


Preservation of allicin :
See http://en.wikipedia.org/allicin
Cutler and Wilson found that an aqueous cream of allicin (0.5 g/L) compared well with 20 g/L of muporicin .
Aqueous cream is essentially an emulsion .

Make your own Allicin Cream :
Spray-on cream from an aerosol can is an emulsion .
Spray it into your bowl , then crush your garlic clove inside the cream emulsion . Hopefully , large enough percentages of the binary components alliin and enzyme alliinase are encapsulated by the lipid foams .
Smear it on , and as the foams evaporate and break down , the components interact .
Voila , allicin .
Dosages and timing will have to be found by experiment .
Be careful and err on the side of caution . 0.5 g/L allocin is kinda small .

An added advantage is that the burning sensation will be much ameliorated (cream is a milk product , which has been found to decrease the burning sensation .)

Smear it on the gums and swirl it (there will be greatly stimulated spit production) . Swallow if necessary . After a prederminate time (start at 2 minutes , then progress in sequence 4 , 8 ,16 , etc) . If discomfort is experienced , swill mouth with coke . Then milk if necessary .

It can be used as a topical cream for anti-fungal and bacteriocidal purposes on the skin.
Do not use it in capsules designed to bypass the stomach , or in suppositories without medical supervision by a really qualified doctor .

This would be like the Terminator loose in LA .

Making pure allicin , alliin and enzyme alliinase
Put clove of garlic in centrifuge test-tube , together with at least 3 balls whose diameter is slightly more than the radius of the test-tube .
Spin .
The relative motions of the balls will crush the garlic , and the centripetal forces will separate the various layers . These can then be tapped individually . But don't loiter too long , as the enzyme at the interface will eventually convert all the aliin into allicin .


Garlic Perles , oils , etc .
These are worthless as far as allicin health benefits are concerned .
These all involve macerating garlic cloves , then dissolving it into an oil .
Reaction between alliin and enzyme alliinase creates allicin . This decays within a matter of hours as set out above . What remains has very little(if any) bio-reactivity

Temperature release :
There might be a temperature release .
An old evolutionary structure would have added the extra "Oomph" of explosive micro-injection of the allicin . Ie an exothermic reaction between alliin and enzyme alliinase .
This gives opportunity of introducing retrovirals , bleach , etc into the teeth and jaw-bones by smearing a minute layer on the tooth , then biting down on the garlic clove (or cream) .

Really, really potent Garlic will blow your socks off !

Bon appetit.

Andre

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Appendix A
Acidity (PH) of some popular drinks .

Diet Mountain Dew 2.95 0.0
Dr. Pepper 2.92 9.64 tsp.
Sprite 2.90 9.29 tsp.
Gatorade (Lemon-Lime) 2.83 5 tsp.
Mountain Dew 2.80 11.07 tsp.
Minute Maid Orange Soda 2.80 11.2 tsp.
Diet Pepsi 2.77 0.0
Diet Coke 2.70 0.0
Powerade 2.63 5.36 tsp.
Pepsi 2.43 9.64 tsp.
Coca-Cola 2.30 9.64 tsp.
Battery Acid (Yikes!) 1.00 (Acidic) 0.0"

"*Acid amounts from the study “Enamel and root surface erosion due to popular U.S. beverages,” 2006. Authors: L. Ehlen, T.A. Marshall, F. Qian, J.J. Warren, J. Wefel, M.M. Hogan, and J.D. Harless. College of Dentistry, University of Iowa, Iowa City and from University of Minnesota School of Dentistry, 2000, Northwest Dentistry Vol 80, No. 2. **4.2 grams = 1 teaspoon."

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Appendix C
Monday, February 11, 2013
Poor man’s cure for diabetes II

Andre Willers

11 Feb 2013

Synopsis :

A pulsed cure is possible .

Discussion :

1.I was horrified to see the costs of gastric bypass (excuse me , bariatric surgery) as the good doctors get onto the bandwagon of curing something they long touted as incurable , but manageable .

2. See Appendix I on how it works .

3.Basically , the peristalsis of the descending duodenum has to be inhibited . But then you have to restart it .

4.We can inhibit that with Imodium or alcohol , or surgically bypassing the descending duodenum .

5.Why I could not try it : the restart is not that simple .

Until I found this :

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

"There is also evidence that 'sham (imitated) feeding', such as chewing gum, may stimulate gastrointestinal motility in the post-operative period.[9]"

6.This restarts the intestinal contraption .

7. The chewing gum should have some sugar , but the main action is the chewing . The mouth chewing sends peptide signals to the gastric muscle walls to get the lead out .

8. This begs the question whether the whole Imodium/alcohol block is necessary .

9 . A continuous stream of chewing and buccal sugar from the signals from the mouth would habituate descending duodenal systems into a stand-down mode . In other words , a cure for diabetes II . Easily tested .

10. If the chewing gum gets tasteless, just sprinkle it with your favourite flavoured sugar .(A big market) . The sugar and chewing is vital .

11. Santa Anna of Alamo fame also gets into it .

http://en.wikipedia.org/wiki/Antonio_L%C3%B3pez_de_Santa_Anna


" Instead, Adams helped to found the chewing gum industry with a product that he called "Chiclets".[17]"

12. Can it be that simple ?

Try it and see .



Chewbacca would know .

Andre



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Appendix I

A Cure for Diabetes

Andre Willers

31 May 2012

Synopsis :

The control-system short-circuit that causes diabetes can be interrupted in humans by a simple surgical procedure . This cures diabetes , insulin resistance and high blood pressure . We try to trace why .

Discussion :

1.Read Appendix I . This is a succinct summation of the state–of-play as at May 2012 .

2.Why should bypassing the duodenum have such drastic effects ?

Because the system outsmarted itself . Too many vital feedback loops are being controlled by the same chemicals . (A similar effect is observed in brain-stress and body-stress systems) . Inappropriate responses are triggered . The system is unstable .

2.1Peristaltic action in the duodenum is accompanied by vasoactive intestinal peptide (VIP) release, a marker for inhibitory neurotransmitter release . See Appendix III . (Note the effect on blood pressure )

But this and PHI release (see Appendix II) affect the Prolactin system ,(seehttp://en.wikipedia.org/wiki/Prolactin ) which is tied to at least 300 other biochemical processes , as well as the prion system (see http://andreswhy.blogspot.com "Prions and the Amygdala" May 2012) .

This whole mess is an unstable system , that can and does go wrong in a large number of ways . And the original trigger can be impossible to trace .

2.2To add insult to injury , the original trigger can cause an amygdala reaction : ie a memory remains in the system , and there few , if any , "OFF" switches . Hence nasties like insulin resistance . There are doubtlessly many more . Amygdala's are notoriously stupid . It is the function of other systems to reprogram them .

See Appendix IV for the ratchet-effect on bloodpressure .

2.3Milk and milk-products can be identified as one of the factors that should cause the system to destabilise .Lactogen breakdown products interfere with some of the feedback loops in the energy metabolism . The result will be idiosyncratic according to individual metabolism , but insulin resistance will ratchet up . (A calf-protection system short-circuits)



What to do ?

Surgery seems a bit drastic . All we want to do is inhibit peristalsis in the duodenum . Food can be massaged through to the jejenum . I can't find a drug that does this selectively , but I am sure there are some .

But in the meantime we are stuck with something like Loperamide (Imodium) . It is like stopping an enormous factory to fix some small problem at the front-end of the production lines .

The following is not medical advice , and you proceed at your own peril .

Use the pulse principle .

1.Fast until the duodenum is empty , (+-6 hours) . No water .

2.Take Loperimide (Imodium) .. This stops peristalsis and release of neuro-markers .

3.Exercise (walking , jogging – this moves food without peristalsis ) . I have no idea what effect this will have on digestion . But no lying in bed allowed .

4.Then eat and drink mildly on low-carb foods . Appetite will be sharply decreased as alternate demand pathways kick in (Cf Atkins , etc) . Drink when thirsty (cf Noakes) . No milk products of any kind .Verboten

5. How often ? I noticed when writing this that this regimen is remarkably similar to religious regimens like Ramadan , Jewish , Christian , Hindu and Buddhist fasts . Two weeks to a month per year seems adequate . This should reprogram some of the systems to at least a modicum of initial states .

6.Monitor blood glucose about 2 hours after eating .

Interesting Asides :

1.Excessive alcohol intake paralyses the pylorus valve between the stomach and the duodenum . The same effect as fasting , in that food does not enter the duodenum to trigger peristalsis . Typically bloated feeling , with big "beer bellies" . Since alcohol is a product of carbohydrates , this is a fascinating adaptation to high carbohydrate intake . 

To put it another way , agricultural farming only took off because periodic alcoholic binges enabled re-normalization of glycemic systems . As this dwindled , so diabetes increased .

2.Milk and Cheese : as use of these increased , systems increasingly crashed in the Prolactin areas . Energy metabolisms became unstable , and auto-immune diseases increased .And you can't reinstate the original system simply by stopping milk products : amygdala's have to be reprogrammed . 

These are but the a sketch of the bare bones of complex mechanism . But at least some indication of where to go or where not to go .

But I refuse to countenance a system that does not allow toasted cheese sandwiches .

There must be a better way .

Andre .

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Appendix I

http://www.calgaryherald.com/health/Curing+diabetes+surgery+without+weight+loss/6704230/story.html


Cristina Iaboni had the dubious distinction of being not quite obese enough. For all the pounds on her 5'5" frame, she did not meet the criteria for bariatric surgery to help control her type 2 diabetes.

Yet six years of medications and attempts at healthy living had failed to rein in her blood glucose, leaving Iaboni terrified that she was on course to have her kidneys fail "and my feet cut off" -- common consequences of uncontrolled diabetes.

Then the 45-year-old Connecticut wife, mother of two and head of human resources for a Fortune 500 company, lucked out. In 2009 she met with Dr Francisco Rubino of Weill Cornell Medical Center in New York. He had just received approval to study experimental surgery on diabetics with a relatively lean weight-to-height ratio, or body-mass index (BMI). Iaboni was among his first subjects.

Three years on, she has dropped 50 pounds to reach a healthy 145 and has normal blood pressure without medication. That isn't too surprising: Weight loss is the purpose of bariatric surgery and often reduces blood pressure. More remarkable, Iaboni no longer has diabetes.

She is not the first patient with diabetes, which can be triggered by obesity, to be cured by weight-loss surgery. But she is a rarity for having it with a BMI well below 35 and over. That's the level at which the American Diabetes Association says surgery "may be considered" and that Medicare and some private insurers cover. And Iaboni's diabetes disappeared months before she shed much weight.

Her experience has raised an intriguing possibility: that some forms of bariatric surgery treat diabetes not by making patients shed pounds. Instead, by rerouting part of the digestive system, they change what signals the gut sends to the brain and the brain sends to the liver, altering the underlying causes of diabetes.

If proven, bariatric surgery may help people with type 2 diabetes who are less obese, overweight or even of healthy weight. And it might be effective against the currently incurable type 1, or "juvenile," diabetes, too.

"Every textbook says that diabetes is chronic, irreversible, and progressive," said Rubino. "But we have thousands of patients who once had diabetes and now do not."

"INSUFFICIENT" EVIDENCE

Bariatric surgeons have long been prone to declaring victory against diabetes way too soon, before large-scale, long-term data proved their case. "The evidence for the success of bariatric surgery in patients with a BMI below 35 is not very strong," said Leonid Poretsky, director of the Friedman Diabetes Institute at Beth Israel Medical Center in New York City. "Most of the studies have been very small and not well controlled."

The American Diabetes Association rates the evidence that bariatric surgery can cure diabetes as "E," the lowest of four grades. It calls data on patients with a BMI below 35 "insufficient," and says the procedure cannot be recommended except as part of research.

The immediate risks of bariatric surgery are small -- a 0.3 per cent chance of dying within 30 days of the procedure. But a small fraction of patients develop infections, leaking from the stomach into the abdominal cavity, or gallstones, and it can cause nutritional deficiencies: There is less intestine to absorb vitamins and minerals, raising the possibility of osteoporosis and anemia.

Despite these red flags, the surgical option is attracting intense interest because the quest to cure diabetes has become almost desperate. In type-1 diabetes, the pancreas does not produce enough insulin, a hormone that moves the glucose in food into cells. In type 2 diabetes, cells become resistant to insulin. In either case, glucose remains in the blood, damaging cells and blood vessels, sometimes severely enough to cause blindness, kidney failure, or gangrene requiring foot or limb amputations.

In 2010, 8.3 per cent of adults worldwide had type 2 diabetes (11.3 per cent did in the United States), resulting in direct medical costs of $376 billion ($116 billion in the United States). By 2030, the global incidence is projected to rise to 9.9 per cent, partly because of the rising obesity rate, with costs reaching $490 billion.

The possibility that bariatric surgery could cure diabetes emerged about a decade ago. A long-term study of thousands of patients in Sweden reported in 2004 that both gastric bypass and banding improved diabetes in many subjects. A 2008 study of 55 obese patients found that 73 per cent of those who underwent gastric banding saw their diabetes disappear after two years, compared to 13 per cent undergoing standard medical treatment such as medication, diet and exercise.

In 2009, surgeons at the University of Minnesota analyzed 621 mostly small studies of bariatric surgery in obese, diabetic patients. Their conclusion, reported in the American Journal of Medicine: 78 per cent no longer needed medication to control their blood sugar. They'd been cured. Lap banding had the worst results, worsening diabetes in some patients.

But most patients in these studies were obese, many morbidly so. (The average BMI was 48.) The improvement in glucose control could therefore be credited to the patients' weight loss, which averaged 85 pounds.

CLUES FROM THE PAST

Rubino had a hunch that something else was at work. As a research fellow in diabetes at Mount Sinai Hospital in New York in 1999, he was reviewing the medical literature one day for guidance on how to best perform bariatric surgery on a man with a BMI of 80. He found papers from the 1950s and earlier reporting that surgery for peptic ulcers had cured diabetes.

Ulcer surgery removes a portion of the stomach and reconstructs a connection to the intestine, much as gastric bypass does. Few diabetes experts had noticed the old papers; they were published in surgery journals, which endocrinologists seldom read.

His serendipitous find led Rubino to other papers describing operations on the digestive tract that cured diabetes, something that, according to medical textbooks, was unthinkable.

"Within two weeks of surgery and sometimes sooner, these patients were off their insulin, off their diabetes drugs, and with normal blood glucose levels," said Rubino. "That was too fast to explain by weight loss."

Yet that's how experts explained bariatric surgery's effect on diabetes, especially as the procedure took hold in the 1990s. Few surgeons focused on how quickly the condition disappeared, said Rubino, "or they speculated that patients weren't eating much after the surgery, and that's what cured their diabetes."

He began pursuing the idea that surgery might improve diabetes directly, rather than through weight loss. "I was ignorant of diabetes, so I wasn't burdened by too much knowledge," Rubino said. "Something that might have seemed heretical didn't seem impossible to me."

Rubino modified the popular gastric bypass surgery, called Roux-en-Y, to test his idea on diabetic lab rodents. In the classic operation, the stomach is pinched off so it can hold less food. Surgical cuts keep the rest of the stomach and the top of the small intestine, called the duodenum, from receiving any food. Instead, the stomach empties directly into the bottom of the small intestine, the jejunum. In Rubino's variation, called duodenal-jejunal bypass (DJB), the stomach is untouched, but the rest of the procedure is the same.

The rats that Rubino operated on beginning in 2000 were cured of diabetes much more quickly than their weight fell. It was the first rigorous evidence, from a well-controlled study, that gut surgery has an anti-diabetes effect.

In 2006, Rubino was ready to move from rats to people. Two patients, with BMIs of 29 and 30, underwent his procedure. Their blood sugar levels returned to normal within days, though they lost no weight. In his most recent trial, reported in March in the New England Journal of Medicine, Rubino and colleagues at Catholic University in Rome performed standard gastric bypass surgery or a procedure similar to DJB on people with type 2 diabetes. After two years, 15 of 20 bypass patients and 19 of 20 DJB patients no longer had diabetes.

Curiously, although patients shed pounds, there was no correlation between weight loss and blood glucose, the key marker of diabetes. "Bariatric surgery is more effective on diabetes than obesity," said Rubino. "Patients don't become lean, but they do not have diabetes anymore."

FROM GUT TO BRAIN

Research from the University of Toronto, reported online this month in Nature Medicine, may finally explain why. It examined the effects of bypass surgery on rats with type-1 diabetes, which is considered even harder to treat than type 2. Normally the jejunum receives only digested mush, as nutrients have already been absorbed in the duodenum, explained lead researcher Tony Lam.

Bypassing the duodenum allows the jejunum to receive an influx of nutrients for the first time, said Lam. Sensing them, the jejunum sends a "got glucose!" signal to the brain. The brain interprets that as a sign of glucose overabundance and orders the liver to decrease glucose production. Result: The rats no longer have diabetes.

"I believe that similar mechanisms are taking place in surgery for type 2 diabetes," said Lam. "It strengthens the case for the surgery treating diabetes independent of weight loss."

His rat study shows why lap banding and stomach stapling are less effective against diabetes than gastric bypass. Banding causes diabetes to go into remission in about 50 per cent of patients, probably due to weight loss, said endocrinologist Dr Allison Goldfine of the Joslin Diabetes Center in Boston.

In contrast, the diabetes-remission rate after Roux-en-Y is 80 to 85 per cent. "The improvements in blood glucose with Roux-en-Y appear to occur very early, by day three after surgery, so patients are being discharged with no medication," she said. Something other than weight loss "must be going on."

Goldfine has launched a study of diabetics with BMIs of 30 to 42 to compare outcomes after lap band surgery, Roux-en-Y, and intense medical management.

A year ago, Rubino began the first large study for type 2 diabetes patients with a BMI as low as 26, where "overweight" begins. The cost of the bypass surgery is covered by a grant from Covidien Plc, which makes laparoscopic instruments and surgical staplers. He aims to enroll at least 50 patients, following them for five years; he has operated on 20 so far.

© Copyright (c) Reuters



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Appendix II

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


Peptide PHI (or peptide histidine isoleucine) is a peptide which functions as a hormone.

It plays a role in the regulation of prolactin in humans.[1]



1.  peptide phi
A 27-amino acid peptide with histidine at the N-terminal and isoleucine amide at the C-terminal. The exactamino acid composition of the peptide is species dependent. The peptide is secreted in the intestine, but is foundin the nervous system, many organs, and in the majority of peripheral tissues. It has a wide range of biological actions, affecting the cardiovascular, gastrointestinal, respiratory, and central nervous systems.


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Appendix III

http://jpet.aspetjournals.org/content/307/2/460.short


Neurotransmitters Mediating the Intestinal Peristaltic Reflex in the Mouse

1.             John R. Grider

+Author Affiliations

2.             Address correspondence to:
Dr. J. R. Grider, Department of Physiology, P.O. Box 980551, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298. E-mail: jgrider@hsc.vcu.edu
Abstract

The motor, modulatory, and sensory neurotransmitters that mediate the peristaltic reflex in the mouse colon were identified by direct measurement, and their involvement in various pathways was determined by selective receptor antagonists. Mucosal stimulation in the central compartment of a three-compartment flat sheet preparation of mouse colon elicited ascending contraction and descending relaxation in the orad and caudad compartments, respectively. Ascending contraction was accompanied by substance P release, a marker for excitatory neurotransmitter release, into the orad compartment and was partly inhibited by atropine and spantide, and abolished by a combination of the two antagonists.

Descending relaxation was accompanied by vasoactive intestinal peptide (VIP) release, a marker for inhibitory neurotransmitter release, into the caudad compartment, 

and was partly inhibited by VIP10-28 and NG-nitro-L-arginine, and abolished by a combination of the two agents. Somatostatin release increased during descending relaxation: immunoneutralization of somatostatin or blockade of its effect with a selective somatostatin type 2 receptor antagonist inhibited descending relaxation. The δ-opioid receptor antagonist naltrindole augmented descending relaxation and ascending contraction. Calcitonin gene-related peptide (CGRP) release increased in the central compartment and was mediated by concurrent release of 5-hydroxytryptamine (5-HT) because its release was blocked by a 5-HT4 receptor antagonist. Both the latter and the CGRP antagonist CGRP8-37, inhibited ascending contraction and descending relaxation. Thus, the reflex in mouse like that in rat and human intestine is initiated by mucosal release of 5-HT and activation of 5-HT4 receptors on CGRP sensory neurons and is relayed via somatostatin and opioid interneurons to VIP/nitric-oxide synthase inhibitory motor neurons and via cholinergic interneurons to acetylcholine/tachykinin excitatory motor neurons.



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Appendix IV



Peptides. 1984 May-Jun;5(3):593-606.

Co-existence of peptide HI (PHI) and VIP in nerves regulating blood flow and bronchial smooth muscle tone in various mammals including man.

Lundberg JMFahrenkrug JHökfelt TMartling CRLarsson OTatemoto KAnggård A.
Abstract
By immunohistochemistry it was found that PHI- and VIP-like immunoreactivity (-IR) occurred in the same autonomic neurons in the upper respiratory tract, tongue and salivary glands with associated ganglia in rat, guinea-pig, cat, pig and man. VIP- and PHI-like immunoreactivity was also found in similar locations in the human heart. The N-terminally directed, but not the C-terminally directed, PHI antiserum or the VIP antiserum stained endocrine cells in the pig duodenum. This suggests the existence of an additional PHI-like peptide. Ligation of nerves acutely caused marked overlapping axonal accumulations of PHI- and VIP-IR central to the lesion. Two weeks after transection of the nerves, both types of immunoreactivities were still observed in accumulations both in the axons as well as in the corresponding cell bodies. The levels of PHI- and VIP-IR in normal tissues from the cat were around 10-50 pmol/g with a molar ratio of about 1 to 2. Systemic administrations of PHI and VIP induced hypotension, probably due to peripheral vasodilation in both guinea-pig and cat. Furthermore, both PHI and VIP caused an inhibition of the vagally induced increase in respiratory insufflation pressure in guinea-pig. PHI and VIP relaxed the guinea-pig trachea in vitro, suggesting a direct action on tracheobronchial smooth muscle. VIP was about 5-10 times more potent than PHI with regard to hypotensive effects and 2-3-fold, considering respiratory smooth muscle-relaxant effects in the guinea-pig. PHI was about 50-fold less potent to induce hypotension in the cat than in the guinea-pig. Although species differences seem to exist as regards biological potency, PHI should also be considered when examining the role of VIP as an autonomic neurotransmitter.
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Appendix D


Human Nose Can Detect a Trillion Smells
20 March 2014 2:00 pm

Zach Veilleux/The Rockefeller University
One in a trillion. The vials of smells that volunteers sniffed in the new study were only a tiny sampling of all the possible smells that humans can distinguish.
A rose, a fresh cup of coffee, a wood fire. These are only three of the roughly 1 trillion scents that the human nose and brain are capable of distinguishing from each other, according to a new study. Researchers had previously estimated that humans could sense only about 10,000 odors but the number had never been explicitly tested before.
“People have been talked into this idea that humans are bad at detecting smells,” says neurobiologist Leslie Vosshall of Rockefeller University in New York City, who led the new work. “So these findings should give the whole human race a confidence boost.”
Humans detect smells by inhaling air that contains odor molecules, which then bind to receptors inside the nose, relaying messages to the brain. Most scents are composed of many odorants; a whiff of chocolate, for example, is made up of hundreds of different odor molecules. Understanding how people process the complex information contained in scents—or memories of smells—offers a window into how the human brain functions.
Vosshall says she and others in the field had long guessed that the number of detectable scents often cited in the literature, based on rough calculations made in the 1920s of the known groups and ranges of smells—claiming that humans could distinguish 10,000 odors—was way off. So her lab decided to test it once and for all. They took 128 odor molecules that represented a wide range of smells and started combining them into unique mixtures containing 10, 20, or 30 different components. Then, they recruited volunteers from the community, aged 20 to 48, to start sniffing the mixtures. “The people we invited to do this study were not professionals; they were not wine tasters or perfumers,” Vosshall says.
Each volunteer was given three smell-containing vials at a time—two that were identical and one that was a slightly different mixture—and then was asked which was the odd one out. On average, if the components varied by more than 50%, the scientists found, people could distinguish the smells as different. When Vosshall’s team crunched these numbers, extrapolating how many different combinations of the 128 odorants an average person could differentiate, they arrived at an average of 1 trillion smells.
Individual performance, however, varied, they report online today in Science. The researchers calculated that the least successful smeller in the study would be able to smell only 80 million unique scents. And the best performer had a far more sensitive sense of smell, likely able to distinguish more than a thousand trillion odors.
The ability to distinguish a trillion scents from one another when they’re paired up, though, doesn’t mean that humans can identify a trillion different scents, says neurologist Jay Gottfried of the Northwestern University Feinberg School of Medicine in Chicago, Illinois. “Even if humans can distinguish that many odors based on these projected mixtures, I don’t know if there are really 1 trillion unique odors in the world that we would need to be discriminating.”
Gottfried adds, however, that the study brings up interesting questions regarding how complex smells are sensed by the nose and brain. “In general, it highlights a growing interest in how combinations of odors—rather than single odor molecules at a time—are sensed and processed.”
Vosshall and her colleagues are pursuing some of these questions, including whether certain combinations of odors are indistinguishable despite being very different at a molecular level. But for now, she just hopes the new findings encourage people to take another sniff at the world around them.
“Knowing we have these capabilities, I hope people, as they go about their business, start saying, ‘Hey, I can smell all these things.’ Maybe the companies that make scented products will start making greater use of the human capacity and develop cleaners and perfumes with new, more interesting scents,” she says. “Maybe we’re going to start using those corners of our smell capacity that have just not been exercised lately.”
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