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Health Items from 2009:                                                  to enlarge a photo, click on it

Medical Myths   Alzheimers 4 - Getting old  Cured Dyslexics   Vitamin D   Celiac and skin conditions  Holy Powder  
What APP does  Celiac Insights   Too clean for our own good  Maybe the molecule of the century  Bile acid  Is Christmas a hazard to your health?     

Medical Myths
A recent study has shown that many 'truths' believed by the public and by medical professionals, including doctors, are false.
1.  Sugar makes kids hyperactive.
2.  Suicides increase over the holidays.
3.  Poinsettias are toxic.
4.  You lose most of your body heat through your head. (only if your head is the main uncovered part of your body)
5.  Eating at night makes you fat. (only if it increases your total calorie intake for the day)
6.  You can cure a hangover with… (there is no effective hangover cure)
The researchers themselves were surprised that some of these were false.

Alzheimers 4 - Getting old
Age is a risk factor for many neurodegenerative diseases, such as Alzheimer’s. A protein called MOCA (Modifier of Cell Adhesion) has been identified as key. It is also known as DOCK3 (Dedicator of cytokinesis protein 3), PBP (Presenilin-binding protein) and KIAA0299. MOCA is found in neurons and the amount decreases with age. The protein has a long list of actions. The one that may be at the heart of neuron death is MOCA’s protection of the cytoskeleton in the long axons. In Alzheimers, ALS and Huntington’s the disease involves the degeneration of axons and eventually working up to the cell body itself.
“After documenting the sequence of physiological and behavioral events that characterize the axon degeneration, Chen then sought to piece together the molecular pathway behind it, starting with MOCA and connecting findings from disparate studies that previously had identified parts of the pathway. He ended up with a single, step-by-step process for axon degeneration that for the first time linked together a number of diseases and conditions, including a form of mental retardation in humans. Now we know that MOCA is essential to the functional integrity of axons and have defined a complete pathway for axon degeneration."
This should lead to fitting it explanations of other risk factors in the pathway and perhaps treatments.

Cured dyslexics
A group in Holland has been looking at adult dyslexics (who have learned to read) with fMRI scans while they match letters and speech sounds. Although they do the task correctly, their scans differ from normal readers doing the same matching. They have learned to integrate letters and speech sounds but in a different way then non-dyslexics. They appear to make less use of the superior temporal cortex when doing the matching.
This is not research into the causes of dyslexia, whether there is one or many. It is simply looking at how dyslexics do read when they learn to. The front-runner in possible causes is still the inability to properly process phonological sounds. And the most obvious source of this problem is a lack of the fast pathway in analyzing sounds and therefore the inability to hear the fine structure of speech.
I must say, this different method of reading in cured dyslexics sounds right to me. I have always had the feeling that I was forging a new pathway to reading and spelling – go around some blockage or dead end. Doing what others did to read or spell did not work, no matter how hard or long I tried. So I am not surprised that the mechanisms I use to read and write are somewhat different from others.

Vitamin D
Some are saying that the hype about Vitamin D is unwarranted, but I'm giving it a try. According to the pro vioces -

- Vitamin D deficiency is very common and this is especially true of older women.
- There is revision of the guidelines for vitamin D intake underway – upward.
- Low vitamin D can increase inflammation even in women who appear healthy, but have suboptimal health.
- Vitamin D deficiency has been linked to heart disease, high blood pressure, multiple sclerosis, rheumatoid arthritis, obesity, diabetes, metabolic syndrome, inflammatory bowel disease, chronic liver disease, osteoporosis, muscle weakness, stroke, and perhaps fatigue joint pain, depression, cancer and infections.

The case has not been made for all of these diseases but it is clearly needed for bone and muscle health (including heart muscle). And its connection to inflammation is strong. The reason I take this seriously is that vitamin D is part of the system that regulates calcium in the body and calcium is not just what bones are made of but it is one of the most important signals in many processes, in all cells and in all parts of the body. Calcium metabolism is important. A receptor for Vitamin D in cells is responsible for regulating calcium metabolism and for the transcription of over 900 genes largely to due with immunity.
Some researchers are saying that the link to inflammation may be the other way around. Those with auto-immune disease may have low levels of Vitamin D as a result rather than a cause. They go further and warn that taking ligh doses of vitamin D may actually make auto-immune disease worse.
So I am taking a cautious approach and only having a smallish dose of supplement.

Celiac and Skin Conditions
There are three skin conditions that seem to go with celiac.
The most obvious is dermatitis herpetiformis which has only one cause, inflammation due to glutin intolerance and only one cure, a glutin free diet. Then there is palmoplantar pustulosis which is often associated with glutin intolerance and there is psoriasis where some but not a large proportion of cases are due to glutin intolerance. The symptoms of these conditions are similar but apparently they can be distinguished in biopsy. But how often would a biopsy be done I ask? Dermatitis herpetiformis, and the many cases of palmoplantar pustulosis and the fewer cases of psoriasis that are linked to glutin intolerance, may actually be the same condition. There are antibodies to gliadin (AGA) and inappropriately activiated T- cells attack the skin in these diseases. The same antibodies are found in celiac and the same type of T-cell attack occurs in the gut.
Specifically this is a Th1 immune response to the body's own cells. There are a number of types of T lymphocytes. Th1 produce cytokines that are responsible for killing intracellular parasites (viruses and microorganisms that enter the body's cells) rather than free pathogens and toxins. Interferon gamma is the main Th1 weapon and it causes inflammation. When Th1 lymphocytes recognize normal healthy tissue as a target they cause autoimmune disease.
Why should these skin conditions be slightly different when they have the same cause. One reason may be the lack of some nutrients in celiac. Vitamin A, vitamin C and fatty acids are needed for healthy skin and if these are not absorbed by a damaged gut, the skin may not be as able to withstand the immune attack.
I have what I thought was psoriasis on my face and it got worse slowly over the years. Now it is improving slowly but still there. I also had what was probably the start of palmoplantar pustulosis on my palms but it disappeared shorted after I stopped eating glutin.

Holy Powder
If you love curry like I do, you will like this news. Scientists are finding the reason that the molecule, curcumin, in turmeric spice is good for us. At least four papers have been published in the last few weeks by different groups, all showing the power of curcumin. So like garlic, I can not only eat it and enjoy it, I can approve of myself while I'm doing it.
Turmeric is a bit like snake oil in the number of illnesses in is supposed to cure: bad teeth, bacterial infections, wounds, diarrhea, inflammations, cancers, liver conditions, heart conditions, type2 diabetes, Alzheimers and many others. I was eating quite a lot of it before I was aware that it was supposed to be good for me because I just love the taste. The way I eat it is that I mix curry powder with mayonnaise and put it on boiled egg or whatever I think could go with it. Curry restaurants are not thick on the ground in France so I don't get a proper curry very often.
Here is the news:

Hoorrah for India's holy yellow powder.

What APP does
Biologists knew that amyloid precusor protein (APP) has an important function in the brain but not what it was. Now there is a model of what it does:
APP and a protein called reelin work together to create and maintain synapses in the brain. The synapses are very narrow structures where two neurons almost touch. One neuron releases neurotransmitters into the narrow gap and the other neuron takes them up in order to send signals from the one neuron to the other. This process needs to be controlled and so the synapse is a complicated structure. It appears that APP is like a structural bridge that stabilizes the synaptic space and organizes the flow of neurotransmitters.
When a synapse is no longer needed it is destroyed - the APP bridging is cut apart. This cutting produces amyloid including the beta amyloid associated with Alzheimers disease. Reelin increases the number of dendrites and axons that neurons grow and the synaptic connections between them. It requires APP in order to do this as the two proteins work together.
The search for a Alzheimer treatment or cure is helped by knowledge of the functions of the various proteins involved.

Celiac Insights
Here is the full text of an article in the Scientific American Magazine from its website July 27 2009 - Study of a potentially fatal food-triggered disease has uncovered a process that may contribute to many autoimmune disorders – Scientific American Magazine July 27 2009. It is written by Alessio Fasano.

Celiac Disease Insights: Clues to Solving Autoimmunity

My vote for the most important scientific revolution of all time would trace back 10,000 years ago to the Middle East, when people first noticed that new plants arise from seeds falling to the ground from other plants—a realization that led to the birth of agriculture. Before that observation, the human race had based its diet on fruits, nuts, tubers and occasional meats. People had to move to where their food happened to be, putting them at the mercy of events and making long-term settlements impossible.
Once humans uncovered the secret of seeds, they quickly learned to domesticate crops, ultimately crossbreeding different grass plants to create such staple grains as wheat, rye and barley, which were nutritious, versatile, storable, and valuable for trade. For the first time, people were able to abandon the nomadic life and build cities. It is no coincidence that the first agricultural areas also became "cradles of civilization."

This advancement, however, came at a dear price: the emergence of an illness now known as celiac disease (CD), which is triggered by ingesting a protein in wheat called gluten or eating similar proteins in rye and barley. Gluten and its relatives had previously been absent from the human diet. But once grains began fueling the growth of stable communities, the proteins undoubtedly began killing people (often children) whose bodies reacted abnormally to them. Eating such proteins repeatedly would have eventually rendered sensitive individuals unable to properly absorb nutrients from food. Victims would also have come to suffer from recurrent abdominal pain and diarrhea and to display the emaciated bodies and swollen bellies of starving people. Impaired nutrition and a spectrum of other complications would have made their lives relatively short and miserable.

If these deaths were noticed at the time, the cause would have been a mystery. Over the past 20 years, however, scientists have pieced together a detailed understanding of CD. They now know that it is an autoimmune disorder, in which the immune system attacks the body’s own tissues. And they know that the disease arises not only from exposure to gluten and its ilk but from a combination of factors, including predisposing genes and abnormalities in the structure of the small intestine.

What is more, CD provides an illuminating example of the way such a triad—an environmental trigger, susceptibility genes and a gut abnormality—may play a role in many autoimmune disorders. Research into CD has thus suggested new types of treatment not only for the disease itself but also for various other autoimmune conditions, such as type 1 diabetes, multiple sclerosis and rheumatoid arthritis.

Early Insights

After the advent of agriculture, thousands of years passed before instances of seemingly well-fed but undernourished children were documented. CD acquired a name in the first century A.D., when Aretaeus of Cappadocia, a Greek physician, reported the first scientific description, calling it koiliakos, after the Greek word for “abdomen,” koelia. British physician Samuel Gee is credited as the modern father of CD. In a 1887 lecture he described it as “a kind of chronic indigestion which is met with in persons of all ages, yet is especially apt to affect children between one and five years old.” He even correctly surmised that “errors in diet may perhaps be a cause.” As clever as Gee obviously was, the true nature of the disease escaped even him, as was clear from his dietary prescription: he suggested feeding these children thinly sliced bread, toasted on both sides.

Identification of gluten as the trigger occurred after World War II, when Dutch pediatrician Willem-Karel Dicke noticed that a war-related shortage of bread in the Netherlands led to a significant drop in the death rate among children affected by CD—from greater than 35 percent to essentially zero. He also reported that once wheat was again available after the conflict, the mortality rate soared to previous levels. Following up on Dicke’s observation, other scientists looked at the different components of wheat, discovering that the major protein in that grain, gluten, was the culprit.

Turning to the biological effects of gluten, investigators learned that repeated exposure in CD patients causes the villi, fingerlike structures in the small intestine, to become chronically inflamed and damaged, so that they are unable to carry out their normal function of breaking food down and shunting nutrients across the intestinal wall to the bloodstream (for delivery throughout the body). Fortunately, if the disease is diagnosed early enough and patients stay on a gluten-free diet, the architecture of the small intestine almost always returns to normal, or close to it, and gastrointestinal symp­toms disappear.

In a susceptible person, gluten causes this inflammation and intestinal damage by eliciting activity by various cells of the immune system. These cells in turn harm healthy tissue in an attempt to destroy what they perceive to be an infectious agent.

A Diagnostic Discovery

Fuller details of the many mechanisms through which gluten affects immune activity are still being studied, but one insight in particular has already proved useful in the clinic: a hallmark of the aberrant immune response to gluten is production of antibody molecules targeted to an enzyme called tissue transglutaminase. This enzyme leaks out of damaged cells in inflamed areas of the small intestine and attempts to help heal the surrounding tissue.

Discovery that these antibodies are so common in CD added a new tool for diagnosing the disorder and also allowed my team and other researchers to assess the incidence of the disease in a new way—by screening people for the presence of this antibody in their blood. Before then, doctors had only nonspecific tests, and thus the most reliable way to diagnose the disease was to review the patient’s symptoms, confirm the intestinal inflammation by taking a biopsy of the gut, and assess whether a gluten-free diet relieved symptoms. (Screening for antibodies against gluten is not decisive, because they can also occur in people who do not have CD.)

For years CD was considered a rare disease outside of Europe. In North America, for example, classic symptoms were recognized in fewer than one in 10,000 people. In 2003 we published the results of our study—the largest hunt for people with CD ever conducted in North America, involving more than 13,000 people. Astoundingly, we found that one in 133 apparently healthy subjects was affected, meaning the disease was nearly 100 times more common than had been thought. Work by other researchers has confirmed similar levels in many countries, with no continent spared.

How did 99 percent of cases escape detection for so long? The classical outward signs—persistent indigestion and chronic diarrhea—appear only when large and crucial sections of the intestine are damaged. If a small segment of the intestine is dysfunctional or if inflammation is fairly mild, symptoms may be less dramatic or atypical.

It is also now clear that CD often manifests in a previously unappreciated spectrum of symptoms driven by local disruptions of nutrient absorption from the intestine. Disruption of iron absorption, for example, can cause anemia, and poor folate uptake can lead to a variety of neurological problems. By robbing the body of particular nutrients, CD can thus produce such symptoms as osteoporosis, joint pain, chronic fatigue, short stature, skin lesions, epilepsy, dementia, schizophrenia and seizure.

Because CD often presents in an atypical fashion, many cases still go undiagnosed. This new ability to recognize the disease in all its forms at an early stage allows gluten to be removed from the diet before more serious complications develop.

From Gluten to Immune Dysfunction

Celiac disease provides an enormously valuable model for understanding autoimmune disorders because it is the only example where the addition or removal of a simple environmental component, gluten, can turn the disease process on and off. (Although environmental factors are suspected of playing a role in other autoimmune diseases, none has been positively identified.)

To see how gluten can have a devastating effect in some people, consider how the body responds to it in most of the population. In those without CD, the body does not react. The normal immune system jumps into action only when it detects significant amounts of foreign proteins in the body, reacting aggressively because the foreigners may signal the arrival of disease-causing microorganisms, such as bacteria or viruses.

A major way we encounter foreign proteins and other substances is through eating, and immune soldiers sit under the epithelial cells that line the intestine (enterocytes), ready to pounce and call in reinforcements. One reason our immune system typically is not incited by this thrice-daily protein invasion is that before our defenses encounter anything that might trouble them, our gastrointestinal system usually breaks down most ingested proteins into standard amino acids—the building blocks from which all proteins are constructed.

Gluten, however, has a peculiar structure: it is unusually rich in the amino acids glutamine and proline. This property renders part of the molecule impervious to our protein-chopping machinery, leaving small protein fragments, or peptides, intact. Even so, in healthy people, most of these peptides are kept within the gastrointestinal tract and are simply excreted before the immune system even notices them. And any gluten that sneaks across the gastrointestinal lining is usually too minimal to excite a significant response from a normally functioning immune system.

CD patients, on the other hand, have inherited a mix of genes that contribute to a heightened immune sensitivity to gluten. For example, certain gene variants encoding proteins known as histocompatibility leukocyte antigens (HLAs) play a role. Ninety-five percent of people with CD possess the gene either for HLA-DQ2 or for HLA-DQ8, whereas just 30 to 40 percent of the general population have one of those versions. This finding and others suggest that the HLA-DQ2 and HLA-DQ8 genes are not the sole cause of immune hyperactivity but that the disease, nonetheless, is nearly impossible to establish without one of them. The reason these genes are key becomes obvious from studies of the function of the proteins they specify.

The HLA-DQ2 and HLA-DQ8 proteins are made by antigen-presenting cells. These immune sentinels gobble up foreign organisms and proteins, chop them, fit selected protein fragments into grooves on HLA molecules, and display the resulting complexes on the cell surface for perusal by immune system cells called helper T lymphocytes. T cells that can recognize and bind to the displayed complexes then call in reinforcements.

In patients with CD, tissue transglutaminase released by intestinal epithelial cells attaches to undigested gluten and modifies the peptides in a way that enables them to bind extremely strongly to DQ2 and DQ8 proteins. In consequence, when antigen-presenting cells under intestinal epithelial cells take up the complexes of tissue transglutaminase and gluten, the cells join the gluten to the HLAs and dispatch them to the cell surface, where they activate T cells, inducing the T cells to release cytokines and chemokines (chemicals that stimulate further immune activity). These chemicals and enhancement of immune defenses would be valuable in the face of a microbial attack, but in this instance they do no good and harm the intestinal cells responsible for absorbing nutrients.

CD patients also tend to have other genetic predispositions, such as a propensity for overproducing the immune stimulant IL-15 and for harboring hyperactive immune cells that prime the immune system to attack the gut in response to gluten.

Guilt by Association

What role might antibodies to tissue transglutaminase play in this pathological response to gluten? The answer is still incomplete, but scientists have some idea of what could happen. When intestinal epithelial cells release tissue transglutaminase, B cells of the immune system ingest it—alone or complexed to gluten. They then release antibodies targeted to the enzyme. If the antibodies home in on tissue transglutaminase sitting on or near intestinal epithelial cells, the antibodies might damage the cells directly or elicit other destructive processes. But no one yet knows whether they, in fact, cause such harm.

In the past nine years my colleagues and I have learned that unusual intestinal permeability also appears to participate in CD and other autoimmune diseases. Indeed, a growing body of evidence suggests that virtually the same trio of factors underpins most, and perhaps all, auto­immune diseases: an environmental substance that is presented to the body, a genetically based tendency of the immune system to overreact to the substance, and an unusually permeable gut.

Finding the Leak

It is fair to say that the theory that a leaky gut contributes to CD and autoimmunity in general was initially greeted with great skepticism, partly because of the way scientists thought of the intestines. When I was a medical student in the 1970s, the small intestine was described as a pipe composed of a single layer of cells connected like tiles with an impermeable “grout,” known as tight junctions, between them. The tight junctions were thought to keep all but the smallest molecules away from the immune system components in the tissue underlying the tubes. This simple model of the tight junctions as inert, impermeable filler did not inspire legions of researchers to study their structure, and I was among the unenthused.

It was only an unexpected twist of fate, and one of the most disappointing moments of my career, that drew me to study tight junctions. In the late 1980s I was working on a vaccine for cholera. At that time, the cholera toxin was believed to be the sole cause of the devastating diarrhea characteristic of that infection. To test this hypothesis, my team deleted the gene encoding the cholera toxin from the bacterium Vibrio cholerae. Conventional wisdom suggested that bacteria disarmed in this way would make an ideal vaccine, because the remaining proteins on a living bacterial cell would elicit a strong immune response that would protect against diarrhea.

But when we administered our attenuated bacteria to volunteers, the vaccine provoked enough diarrhea to bar its use. I felt completely disheartened. Years of hard work were literally down the toilet, and we were faced with two unattractive options: giving up and moving on to another research project or persevering and trying to understand what went wrong. Some in­tuition that there was more to this story prompted us to choose the latter path, and this decision led us to discover a new toxin that caused diarrhea by a previously undescribed mechanism. It changed the permeability of the small intestine by disassembling those supposedly inert tight junctions, an effect that allowed fluid to seep from tissues into the gut. This “grout” was interesting after all.

Indeed, at nearly the same time, a series of seminal discoveries clarified that a sophisticated meshwork of proteins forms the tight junctions; however, little information was available on how these structures were controlled. Therefore, the discovery of our toxin, which we called the “zonula occludens toxin,” or Zot (zonula occludens is Latin for “tight junction”), provided a valuable tool for clarifying the control process. It revealed that a single molecule, Zot, could loosen the complex structure of the tight junctions. We also realized that the control system that made this loosening possible was too complicated to have evolved simply to cause biological harm to the host. V. cholerae must cause diarreha by exploiting a preexisting host pathway that regulates intestinal permeability.
Five years after the formulation of this hypothesis, we discovered zonulin, the protein that in humans and other higher animals increases intestinal permeability by the same mechanism as the bacterial Zot. How the body uses zonulin to its advantage remains to be established. Most likely, though, this molecule, which is secreted by intestinal epithelial tissue as well as by cells in other organs (tight junctions have important roles in tissues throughout the body), performs several jobs—including regulating the movement of fluid, large molecules and immune cells between body compartments.
Discovery of zonulin prompted us to search the medical literature for human disorders characterized by increased intestinal permeability. It was then that we first learned, much to my surprise, that many autoimmune diseases—among them, CD, type 1 diabetes, multiple sclerosis, rheumatoid arthritis and inflammatory bowel diseases—all have as a common denominator aberrant intestinal permeability. In many of these diseases, the increased permeability is caused by abnormally high levels of zonulin. And in CD, it is now clear that gluten itself prompts exaggerated zonulin secretion (perhaps because of the patient’s genetic makeup).
This discovery led us to propose that it is the enhanced intestinal permeability in CD patients that allows gluten, the environmental factor, to seep out of the gut and to interact freely with genetically sensitized elements of the immune system. That understanding, in turn, suggests that removing any one factor of the autoimmunity-causing trinity—the environmental trigger, the heightened immune reactivity or the intestinal per­meability—should be enough to stop the disease process.
Therapies to Topple the Trinity

As I mentioned before, and as this theory would predict, removing gluten from the diet ends up healing the intestinal damage. Regrettably, a lifelong adherence to a strict gluten-free diet is not easy. Gluten is a common and, in many countries, unlabeled ingredient in the human diet. Further complicating adherence, gluten-free products are not widely available and are more expensive than their gluten-containing counterparts. In addition, sticking perfectly over years to any diet for medical purposes is notoriously challenging. For such reasons, diet therapy is an incomplete solution. Consequently, several alternative therapeutic strategies have been considered that disrupt at least one element of the three-step process. Alvine Pharmaceuticals in San Carlos, Calif., has developed oral protein-enzyme therapies that completely break down gluten peptides normally resistant to digestion and has an agent in clinical trials. Other investigators are considering ways to inhibit tissue transglutaminase so that it does not chemically modify undigested gluten fragments into the form where they bind so effectively to HLA-DQ2 and HLA-DQ8 proteins.
No one has yet come up with safe and ethical ways to manipulate the genes that make people susceptible to disease. But researchers are busy developing therapies that might dampen some of the genetically controlled factors that contribute to the immune system’s oversensitivity. For example, the Australian company Nexpep is working on a vaccine that would expose the immune system to small amounts of strongly immunogenic forms of gluten, on the theory that repeated small exposures would ultimately induce the immune system to tolerate gluten.With an eye toward blocking the intestinal barrier defect, I co-founded Alba Therapeutics to explore the value of a zonulin inhibitor named Larazotide. (I am now a scientific adviser for Alba and hold stock options, but I no longer participate in making decisions for the company.) Larazotide has now been tested in two human trials examining safety, tolerability and signs of efficacy in celiac patients who ate gluten. These were gold-standard trials—randomized, placebo-controlled tests in which neither the drug deliverers nor the patients know who receives treatment and who receives a sham, until the trial is over.Together the tests showed no excess of side effects in patients given Larazotide rather than the placebo. More important, the first, smaller study demonstrated that the agent reduced gluten-induced intestinal barrier dysfunction, production of inflammatory molecules and gastrointestinal symptoms in celiac patients. And the second, large study, reported at a conference in April, showed that CD patients who received a placebo produced antibodies against tissue transglutaminase but that the treated group did not. As far as I know, this result marks the first time a drug has halted an autoimmune process, interfering specifically with an immune response against a particular molecule made by the body. Other drugs that suppress immune activity act less specifically. Recently Alba received approval from the U.S. Food and Drug Administration to expand studies of Larazotide to other autoimmune disorders, including type 1 diabetes and Crohn’s disease.These new prospects for therapy do not mean that CD patients can abandon dietary restrictions anytime soon. Diet could also be used in a new way. Under the leadership of Carlo Catassi, my team at the University of Maryland has begun a long-term clinical study to test whether having infants at high risk eat nothing containing gluten until after their first year can delay the onset of CD or, better yet, prevent it entirely. “High risk,” in this case, means infants possess susceptibility genes and their immediate family has a history of the disorder.
We suspect the approach could work because the immune system matures dramatically in the first 12 months of life and because research on susceptible infants has implied that avoiding gluten during the first year of life might essentially train that developing immune system to tolerate gluten thereafter, as healthy people do, rather than being overstimulated by it. So far we have enrolled more than 700 potentially genetically susceptible infants in this study, and preliminary findings suggest that delaying gluten exposure reduces by fourfold the likelihood that CD will develop. It will be decades, however, until we know for certain whether this strategy can stop the disease from ever occurring.
Given the apparently shared underpinning of autoimmune disorders in general, researchers who investigate those conditions are eager to learn whether some therapeutic strategies for CD might also ease other autoimmune conditions that currently lack good treatments. And with several different approaches in the pipeline to treat CD, we can begin to hope that this disease, which has followed humanity from the dawn of civilization, is facing its last century on earth.
A Clue to Delayed Onset
People with celiac disease are born with a genetic susceptibility to it. So why do some individuals show no evidence of the disorder until late in life? In the past, I would have said that the disease process was probably occurring in early life, just too mildly to cause symptoms. But now it seems that a different answer, having to do with the bacteria that live in the digestive tract, may be more apt. These microbes, collectively known as the microbiome, may differ from person to person and from one population to another, even varying in the same individual as life progresses. Apparently they can also influence which genes in their hosts are active at any given time. Hence, a person whose immune system has managed to tolerate gluten for many years might suddenly lose tolerance if the microbiome changes in a way that causes formerly quiet susceptibility genes to become active. If this idea is correct, celiac disease might one day be prevented or treated by ingestion of selected helpful microbes, or “probiotics.”

Too clean for our own good
Someone (I know him by the name Daedalus) has looked at the items on this page, noticed the diseases I am interested in, and sent me some information on research at Warwick University that he is involved in.
This research is, indeed, interesting to me for a few reasons: it involves microbiology, it involves human evolution, and it involves metabolic syndrome/Alzheimers/auto-immune desease.
One paper* is about the Whitlock-Feelisch Hygiene hypothesis and goes like this:

  1. There is a increase in certain diseases in the affluent, urban, developed world that are not as prevalent in the rural, poor, undeveloped world. The changes in the incidence of these diseases over time points to the cause being better hygiene – more bathing, more soap, more detergents, more disinfectants, cleaner water. 'Good bacteria' are 'old friends' through human evolution and we may depend on some of their good works. Hygiene decreases good as well as bad bacteria.

  2. These diseases involve the immune system and inflammation (asthma, allergies, type 1 diabetes, inflammatory bowel disease, obesity, some degenerative diseases). The conditions are made worse by obesity and by stress. They are probably connected by some common biochemical pathways and regulatory mechanisms of those pathways. The authors put forward the pathways that are regulated by nitric oxide (NO) as a likely set to be responsible from these diseases.

  3. Normal skin bacteria are only now being studied and there are two ways in which they could affect nitric oxide and nitrite: by reduction nitrate (NO3-) to nitrite (NO2-) and by oxidation of ammonia (NH4) to nitrite (NO2-). The later would be done by ammonia oxidizing bacteria. Bacteria in the mouth produce nitrite (NO2-) from nitrate (NO3-) in food and water.

  4. Nitric oxide (NO) is a gas with a signaling role in a number of cellular processes. It diffuses through tissue and where is it above a threshold level activates NO sensors. The enzyme, nitric oxide synthases, produces it from the amino acid L-arginine. The amount produced depends on the amount of reactive oxygen species (peroxide, free radicals, oxygen ions – the sort of chemical that anti-oxidants scavenge). The ratio of nitric oxide and reactive oxygen determines the action of many critical proteins. Nitrite (NO2-) can act like nitric oxide (NO) but is not a gas and so acts only locally as it cannot diffuse through tissue.

  5. The basal level of nitric oxide (NO) gas in the tissues affects the response to any additional signaling gas. A change to basal level will change the range and timing of any signal, 'good regulation with a bad setpoint'. The pathways using NO signals are highly complex and basal level disturbances would affect them all in complex ways. Nitrite (NO2-) shortage and oxidative stress both increase the need for higher NO levels for the same signaling effect. Not only does stress lower NO levels but lower NO heightens stress. The balance of NO and reactive oxygen has complex affects on inflammation. Inflammation is at the root of the type of diseases associated modern hygiene.

  6. Modern hygiene has eliminated ammonia oxidizing bacteria from the skin. These bacteria do not use complex foods and get all their energy and make the molecules they need for growth from oxidation of ammonia (NH4) to nitrite (NO2-). They live on the skin, use the ammonia in sweat and supply nitrite to their host. Scalp, pubic and underarm hair provides the sweat, warmth, humidity and protection from light needed by the ammonia oxidizing bacteria. There are other mutual advantages between us and these bacteria. Without the levels of hygiene we now have, our skin would have these bacteria and they would be supplying NO2- and reducing the problems in NO supply.

  7. Ammonia oxidizing bacteria are safe. Autotrophic bacteria are not infectious because they cannot fed on the organic matter than makes up our cells. They are very slow growing. They are everywhere in the soil and water in the natural world. They are very susceptible to detergents and other hygiene products. Plants take nitrate (NO3-) and produce amino acids. Heterotropic bacteria and other organisms (including us) oxidize amino acids and release ammonia, the ammonia is used by the autotrophic ammonia oxidizing bacteria – it is one of those natural cycles.

  8. Removal of NO from the body is done mainly by hemoglobin and hemoglobin also produces NO3- from NO2- and so any process that takes higher levels of NO or NO2- cannot go on in the presence of hemoglobin. The outer skin lacks hemoglobin and gets oxygen from the air rather than the blood. NO and NO2- delivered to the skin would be available for the regulation of Tcells. The skin could be quite important to the body's immune system.

  9. If NO and NO2- cannot be delivered to the skin by ammonia oxidizing bacteria because of our level of hygiene, then perhaps they could be delivered in creams or powders. However, a cream or powder would not deliver just when needed like bacteria would. There is a company working on bacterial based products (see http://nitroceutic.com)

Daedalus is not alone in finding nitrate, nitrite and nitric oxide metabolism important. Researchers from Michican State and Amsterdam are advocating more plant sourced nitrate and nitrite in the diet for their benefit to the arteries. And researchers in Houston are investigating Chinese herbs for their ability to convert nitrate and nitrite to nitric oxide and thereby treat cardiovascular illness.

* found in The Hygiene Hypothesis and Darwinian Medicine (Rook GAW,ed.) Birkhaeuser Publishing, Basel, 2009 - Soil bacteria, nitrite, and the skin by David R Whitlock and Martin Feelisch

Maybe the molecule of the century
Haptoglobin is a molecule that has been known for many years as a marker of inflammation in the body. Haptoglobin 1 is the original form of the haptoglobin molecule, and scientists believe it evolved 800 million years ago. Haptoglobin 2 is a permutation found only in Homo species. It's believed the mutation occurred in India about 2 million years ago, spreading gradually among increasing numbers of people throughout the world. A few years ago a protein was discovered that was involved in celiac disease and other autoimmune conditions. This protein was called zonulin. It has now been shown that zonulin is the same molecule as the precursor of haptoglobin 2. Precursors usually have no purpose or effect but precursor haptoglobin 2 is different – it opens a gateway in the intestines to let gluten into the body. The body produces antibodies against this foreign gluten and these antibodies, in celiac sufferers, attack the body's own tissues.
Autoimmune disease is very rare in other primates but humans can get more than 70 different forms of autoimmune conditions. It is now believed that the presence of precursor haptoglobin 2 or zonulin in 80% of humans is the reason for the difference between us and other primates. Zonulin is probably the critical missing piece of the puzzle of all the autoimmune diseases, allergies and maybe some cancers, that are related to loss of protective barrier in the gut, the blood-brain barrier and barriers in other areas of the body. The identification of this molecule will probably led to many new treatments.

Bile acid

People who have their gall bladders removed should be warned about bile acid diarrhea.
Bile acids are made in the liver from cholesterol, and move into the gut through the bile duct. There they emulsify fat so that it can be absorbed. The bile acids that are not re-absorbed with fat are eliminated through the large intestine. The production of bile acids is under feedback control so that if more is re-absorbed, less is made. In at least 1 in 100 people, large amounts of bile acid reach the colon, irritate it and cause it to leak water and salt, giving sudden bouts of extreme diarrhea. This type of diarrhea is often not diagnosed or mis-diagnosed.
Problems occur when:
Now that I avoid gluten, I have much less trouble with diarrhea. Occasionally I suffer from it and the symptoms are like those for bile acid diarrhea. This makes sense as I have had my gall bladder removed.

Is Christmas a hazard to your health?
Well, you would think so!!
We get all stressed working ourselves up to Christmas: shopping, planning, cooking, decorating. We worry about money. Kids get ratty. We have lots of little accidents. By the time Christmas comes, most people are a wreck. Then Christmas is the time to over eat, eat the wrong things, over drink, under exercise. Even if we survive without being one of the people who is in a car accident, has a heart attack or commits suicide, it will take the whole week to New Years to regain the feeling of being human and to make peace with the relatives and friends that you have argued with (or even with the boss that you insulted at the works party). Definitely not healthy!
So why not look at Christmas a different way – as therapy.
Here we are in the darkest part of the year and looking forward to the coldest part of winter and you just want to cry. It is just too long to April to bear. Its called SAD, seasonal affective disorder, and it brings depression, fatigue, sleepiness, vague illnesses and aches. SAD is a good name. What we need is a party and there seems to be one near the winter solstice in every culture. We need to get some light, warmth, exercise, good food and negative ions. We need wood fires and flickering candles. We need tacky shiny bobbles. We need music and hugs. We need to feel full of comfort food and mellow with drink. We need less melatonin and more serotonin.
If you feel a little the worse for Christmas then just imagine how you would feel without it.