Dopamine and Serotonin sulfation decreased by low PST

European Journal of Clinical Pharmacology Reduced platelet phenolsulphotransferase activity towards dopamine and 5-hydroxytryptamine in migraine Journal European Journal of Clinical Pharmacology Publisher Springer Berlin / Heidelberg ISSN 0031-6970 (Print) 1432-1041 (Online) Issue Volume 49, Numbers 1-2 / November, 1995 Biomedical and Life Sciences Monday, November 29, 2004 Pharmacokinetics And Disposition Reduced platelet phenolsulphotransferase activity towards dopamine and 5-hydroxytryptamine in migraine A. L. Jones1, G. L. Rubin1, M. W. H. Coughtrie1 Contact Information, R. C. Roberts2, 3 and W. Colvin3 (1) Department of Biochemical Medicine, University of Dundee, Ninewells Hospital and Medical School, DD1 9SY Dundee, Scotland, UK (2) Department of Medicine, University of Dundee, Ninewells Hospital and Medical School, DD1 9SY Dundee, Scotland, UK (3) Department of Neurology, Dundee Royal Infirmary, DD1 9ND Dundee, Scotland, UK Received: 1 August 1994 Accepted: 31 May 1995 Abstract Objective: The sulphation of the neurotransmitters dopamine and 5-hydroxytryptamine, and of the prototypical xenobiotic 4-nitrophenol, by phenolsulphotransferases was measured in platelet homogenates prepared from a group of migraine sufferers and a group of control subjects. Results: The activity of the M form of phenolsulpho-transferase, responsible for the sulphation of dopamine and 5-hydroxytryptamine was significantly reduced in the migraine population, by 28% with dopamine as substrate and by 20% with 5-hydroxytryptamine. The activity of the P form of the enzyme towards 4-nitrophenol was the same in both groups. We also report that the selective inhibition of P form phenolsulpho-transferase by red wine is much more potent than previously thought, with a 2000-fold dilution of dealcoholised red wine having the ability to inhibit sulphation by this enzyme by 50%. Conclusion: Our findings suggest that a reduced capacity for sulphation and inactivation of biogenic amines and catecholamines may be related to susceptibility to migraine.

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From the TacaNow site.

Symptoms of Gluten Intolerance

Is Subclinical Gluten Intolerance/Celiac Disease Sabotaging Your Health? The Celiac Disease/Autoimmune/Thyroid Connection

Gluten intolerance -- also known as celiac disease, celiac sprue, and sprue -- is a genetic autoimmune condition that makes it difficult for the body to properly absorb nutrients from foods. It affects an estimated 1.5 million Americans. What happens in gluten intolerance is: The body lacks a particular digestive enzyme, intestinal glutaminase, that can digest gluten products Gliadin antibodies are produced as the body's reaction to the presence of the gluten the villi in the bowels become flattened, making them less able to sweep along waste products and filter out toxins The bowel, in a state of irritation, becomes more permeable, allowing larger proteins to pass through, which further aggravates the "allergic" response The body responds by producing more histamine, seratonin, kinins, prostaglandins, and interleukins -- which can trigger or aggravate autoimmune and inflammatory conditions The incidence of full-scale gluten intolerance has been found to be substantially higher in people with autoimmune thyroid disease. A study reported on in the February 2000 issue of Digestive Diseases and Sciences found that undiagnosed celiac disease may be part of the process that triggers an underlying autoimmune disease. In their findings they wrote: ""We believe that undiagnosed celiac disease can cause other disorders by switching on some as yet unknown immunological mechanism. Untreated celiac patients produce organ-specific autoantibodies." Of perhaps greatest importance to thyroid patients, those researchers found that the various antibodies that indicate celiac disease - organ-specific autoantibodies (i.e., thyroid antibodies) -- disappear after 3 to 6 months of a gluten-free diet. The researchers suggested that patients with autoimmune thyroiditis "may benefit from a screening for celiac disease so as to eliminate symptoms and limit the risk of developing other autoimmune disorders." Celiac antibodies blood testing can help diagnose the full-scale version of the condition, but formal diagnosis requires biopsy. Because the full-scale diagnosis of the condition is not that common, many doctors and patients do not realize that a milder version of the condition -- subclinical gluten intolerance/celiac disease -- may be the cause of chronic symptoms in millions more thyroid patients. Diagnosing the subclinical, reversible version requires newer "intestinal permeability" or "mucosal barrier" tests, along with clinical observation of symptoms made by an experienced practitioner. What are the symptoms of subclinical gluten intolerance and celiac disease? Recurring abdominal pain and bloating Gas, intestinal difficulties Aggravated allergies Difficulty losing weight Muscle aching Joint stiffness and pain, especially in hands, with swelling Fatigue Burning sensations in the arms and legs Numbness and tingling in hands, arms and legs Brain fog, memory problems, disorganized thinking Sores inside the mouth Painful skin rash on elbows, knees, and buttocks Hives Once diagnosed, the next step is a gluten-free diet. The Gluten Free Diet (Featuring information from the federal government's NIDKK site) The only treatment for celiac disease is to follow a gluten-free diet--that is, to avoid all foods that contain gluten. For most people, following this diet will stop symptoms, heal existing intestinal damage, and prevent further damage. Improvements begin within days of starting the diet, and the small intestine is usually completely healed--meaning the villi are intact and working--in 3 to 6 months. (It may take up to 2 years for older adults.) The gluten-free diet is a lifetime requirement. Eating any gluten, no matter how small an amount, can damage the intestine. This is true for anyone with the disease, including people who do not have noticeable symptoms. Depending on a person's age at diagnosis, some problems, such as delayed growth and tooth discoloration, may not improve. A small percentage of people with celiac disease do not improve on the gluten-free diet. These people often have severely damaged intestines that cannot heal even after they eliminate gluten from their diets. Because their intestines are not absorbing enough nutrients, they may need to receive intravenous nutrition supplements. Drug treatments are being evaluated for unresponsive celiac disease. These patients may need to be evaluated for complications of the disease. If a person responds to the gluten-free diet, the physician will know for certain that the diagnosis of celiac disease is correct. A gluten-free diet means avoiding all foods that contain wheat (including spelt, triticale, and kamut), rye, barley, and possibly oats--in other words, most grain, pasta, cereal, and many processed foods. Despite these restrictions, people with celiac disease can eat a well-balanced diet with a variety of foods, including bread and pasta. For example, instead of wheat flour, people can use potato, rice, soy, or bean flour. Or, they can buy gluten-free bread, pasta, and other products from special food companies. Whether people with celiac disease should avoid oats is controversial because some people have been able to eat oats without having a reaction. Scientists are doing studies to find out whether people with celiac disease can tolerate oats. Until the studies are complete, people with celiac disease should follow their physician or dietitian's advice about eating oats. Plain meat, fish, rice, fruits, and vegetables do not contain gluten, so people with celiac disease can eat as much of these foods as they like. Examples of foods that are safe to eat and those that are not are provided below. The gluten-free diet is complicated. It requires a completely new approach to eating that affects a person's entire life. People with celiac disease have to be extremely careful about what they buy for lunch at school or work, eat at cocktail parties, or grab from the refrigerator for a midnight snack. Eating out can be a challenge as the person with celiac disease learns to scrutinize the menu for foods with gluten and question the waiter or chef about possible hidden sources of gluten. However, with practice, screening for gluten becomes second nature and people learn to recognize which foods are safe and which are off limits. A dietitian, a health care professional who specializes in food and nutrition, can help people learn about their new diet. Also, support groups are particularly helpful for newly diagnosed people and their families as they learn to adjust to a new way of life.

Sulfation, Enzymes, Oxytocin

http://209.85.165.104/search?q=cache:NxDcVeCDi1EJ:www.eas.asu.edu/~autism/Additional/SummaryofDefeatAutismNow.doc+zinc+CCK+oxytocin&hl=en&ct=clnk&cd=3&gl=us Sulfation: Susan Owens substituted for Rosemarie Waring, and presented Dr. Warings data on sulfate in autism. Basically, people with autism were found to excrete roughly twice as much sulfate in their urine, so that they had only 1/5 the normal level of sulfate in their bodies. Sulfur is an essential mineral, and is needed for many functions in the body. AIDS patients have also been found to exhibit a loss of sulfur in their urine, leading to a loss of extracellular sulfated structures in the brain. This has not yet been investigated in autism, but may be the same. In AIDS patients, treatment with N-acetyl cysteine was found to be beneficial. In autism, TNF (tumor necrosis factor) is elevated, which can inhibit the conversion of cysteine to sulfate. Low sulfur levels could cause many problems. o Sulfur is needed to sulfate the hormone CCK, which stimulates oxytocinergic neurons to release oxytocin. So, a lack of sulfur could explain the low oxytocin levels found in autism, which is important for socialization. o Sulphate is important for detoxification of metals and other toxins. o Sulphation requires activated sulfate, which requires magnesium. o Boys excrete more sulfur than girls, so they may be more susceptible to sulfation problems. o Wakefields group found that the ileum of the intestine lacks sulfur, which would lead to a leaky gut. o Sulphate is needed to release pancreatic digestive enzymes. o Many enzymes would be impaired if sulfur levels were low. o The perineuronal nets around neurons, which modulate their function, are primarily composed of chondroitin sulfur. Low sulfur would thus yield less modulation of neurons o The hepatitis B vaccine was found to inhibit sulphation chemistry for one week in typical people.

Mercury and ADD/Autism/Allergies/Immune System

Get your coffee before sitting don to read this one. It's long, but it's full of information! ~L Immune Reactive Conditions: The mercury connection to autism, schizophrenia, ADD, eczema, lupus, asthma, and allergies (snipped from larger study) Bernard Windham- Chemical Engineer The incidence of neurotoxic, allergic, and immune reactive conditions such as autism, scizophrenia, ADD, dyslexia, allergies, asthma, eczema, lupus, psoriasis, childhood diabetes, etc. have been increasing rapidly in recent years(1,2,3,5,23). A recent report by the National Research Council found that 50% of all pregnancies in the U.S. are now resulting in prenatal or postnatal mortality, significant birth defects, or otherwise chronically unhealthy babies(3). Exposure to toxic chemcials or environmental factors appear to be a factor in as much as 28 percent of the 4 million children born each year(3), with 1 in 6 having one of the neurological conditions previously listed.. According to the U.S. FDA, at least 26 million have allergies and at least 17 million have asthma. The largest increase has been in infants (1,2,,5-7,23), with an increase in autism cases to over 500,000 (1,2,23,22), an over 500% increase to a level of almost 1 per 250 infants in the last decade(2), making it the 3rd most common childhood condition, along with similar increases in ADD, and over 10 % of infants- approximately 15 million in the U.S. with such conditions or systemic eczema(1). Studies researching the reason for these rapid increases in infant reactive conditions seem to implicate earlier and higher usage of vaccines containing mercury(thimerosal) as a likely connection(2,2b,23,30,40). A recent study comparing pre- and post-vaccination mercury levels, found a significant increase in both preterm and term infants after vaccination(42), with post-vaccination mercury levels approximately 3 times higher in the preterm infants as compared with term infants. The study found mercury blood levels up to 23.6 ug/L and received an average dose of 16.7 ug/kg. Just this one vaccination gave an exposure to mercury that is many times the U.S. ATSDR adult minimum risk level(MRL) for mercury of .3/ug/kg body weight per day(41). It has been estimated that if all of the vaccines recommended by the American Assoc. of Pediatrics are given and contain thimerosal, then by age 6 months an infant would have received 187 micrograms of ethyl mercury which is more than the EPA/ATSDR health standard for organic mercury(33,41) and by age 3 the typical child has received over 235 micrograms of mercury thimerosal from vaccinations which is considerably more than Federal mercury safety guidelines (41), in addition to significant levels from other sources for many(23). Infants during this period have undeveloped blood brain barriers and much of the mercury goes to the brain, resulting in significant adverse neurological effects in those that are most susceptible(43,3). Because of the evidence the FDA has completed a study and written a letter to vaccine manufacturers asking that mercury be removed from vaccines. The updated letter stated, "The Center for Biologics Evaluation and Research (CBER) has completed its evaluation of the use of thimerosal in vaccines...Our review concluded that reducing or eliminating thimerosal from vaccines is merited(44). The letter pointed to a joint statement by the American Academy of Pediatrics and the United States Public Health Service in 1999, which "called for the removal of thimerosal from vaccines as soon as possible." Many thousands of parents have reported that their child got such conditions after vaccination, and tests have confirmed high levels of mercury in Many of those tested, along with other toxic exposures. An additional source of thimerosal to the fetus of women who are RH negative is the 30 micrograms in the RhoGAM shot they receive. Underweight infants that get the same dose of thimerosal as other infants have also been found to be at special risk. Many of those diagnosed with high mercury levels have also been found to have significant improvement after mercury detoxification(23,30,40,11,35). Thimerosal had been previously removed from similar preservative uses in eye drops and eye medications after evidence of a connection to chronic degenerative eye conditions. After over 15,000 law suits were filed in France over adverse effects of the Hepatitis B vaccine, the French Minister of Health ended the mandatory hepatitis B vaccination program for all school children. Adverse effects included neurological disorders and autoimmune disorders such as multiple sclerosis and lupus. Some hospitals in the U.S. also quit recommending certain vaccinations. Although vaccinations appear to be the largest source of mercury in infants, mercury has been found to be transmitted from the mother to the fetus through the placenta and accumulate in the fetus to higher levels than in the mother’s blood(22). Breast milk of women who have amalgam fillings or eat a lot of fish has also been found to be a significant source of mercury in infants and young children(22,45). A direct mechanism involving mercury’s inhibition of cellular enzymatic processes by binding with the hydroxyl radical(SH) in amino acids appears to be a major part of the connection to these allergic/immune reactive conditions (15-23,36,46). For example mercury has been found to strongly inhibit the activity of xanthine oxidase and dipeptyl peptidase (DPP IV) which are required in the digestion of the milk protein casein(15,16,17,19,20,22), and the same protein that is cluster differentiation antigen 26 (CD26) which helps T lymphocyte activation. CD26 or DPPIV is a cell surfact glycoprotein that is very susceptible to inactivation by mercury binding to its cysteinyl domain. Mercury and other toxic metals also inhibit binding of opioid receptor agonists to opioid receptors, while magnesium stimulates binding to opioid receptors (15). Studies involving a large sample of patients with autism, scizophrenia, or mania found that over 90 % of those tested had high levels of the milk protein beta-casomorphin-7 in their blood and urine and defective enzymatic processes for digesting milk protein(24,25,27), and similarly for the corresponding enzyme needed to digest wheat gluten(24,26).The studies found high levels of Ig A antigen specific antibodies for casein, lactalbumin and beta-lactoglovulin and IgG and IgM for casein. Beta-casomorphine-7 is a morphine like compound that results in neural dysfunction (24,25), as well as being a direct histamine releaser in humans and inducing skin reactions (14,21,25c). Similarly many also had a corresponding form of gluten protein (26). Elimination of milk and wheat products and sulfur foods from the diet has been found to improve the condition. A double blind study using a potent opiate antagonist, naltrexone(NAL), produced significant reduction in autistic symptomology among the 56% most responsive to opioid effects(28). The behavioral improvements was accompanied by alterations in the distribution of the major lymphocyte subsets, with a significant increase in the T-helper- inducers and a significant reduction of the T-cytotoxic-suppressors and a normalization of the CD4/CD8 ratio. Studies have found mercury causes increased levels of the CD8 T-cytotoxic-suppressors(29). As noted previously, such populations of patients have also been found to have high levels of mercury and to recover after mercury detox(23,11,22,30,40). As mercury levels are reduced the protein binding is reduced and improvement in the enzymatic process occurs(22,11). Additional cellular level enzymatic effects of mercury’s binding with proteins include blockage of sulfur oxidation processes and neurotransmitter amino acids which have been found to be significant factors in many autistics(18,36,46,17), plus enzymatic processes involving vitamins B6 and B12, with effects on the cytochrome-C energy processes as well. Epson salts(magnesium sulfate)baths, supplementation with the p5p form of Vit B6 and vit B12 shots are methods of dealing with these enzymatic blockages that have been found effective by those treating such conditions. Mercury has also been found to have adverse effects on cellular mineral levels of calcium, magnesium, zinc, and lithium(39,22,46). Supplementing with these minerals has also been found to be effective in the majority of cases(39) Another of the results of these toxic exposures and enzymatic blockages is the effect on the liver and disfunction of the liver detoxification processes which autistic children have been found to have (30,36,22). All of the autistic cases tested were found to have high toxic exposures/effects and liver detoxification profiles outside of normal(30). Along with these blockages of cellular enzymatic processes, mercury has been found to cause additional neurological and immune system effects in many through immune/autoimmune reactions(11,12,35). Mercury(22) as well as thimerosal (31,32) also have direct neurotoxic effects on brain nucleotid binding proteins through their effect on Ca2+ATPase and Na+/K+ATPase activity. But the effects on the neurological and immune systems of exposure to various toxic substances such as toxic metals and environmental pollutants has also been found to have additive or synergistic effects and to be a factor in increasing eczema, allergies, asthma, delayed food allergies, and sensitivity to other lesser allergens(14-22,35). Most of the children tested for toxic exposures have found high or reactive levels of other toxic metals, and organochlorine compounds (30,40,11,12,35,4). Other than the organochlorines or toxic metals which are discussed later, three common pollutants that have been documented to have effects on such conditions are traffic and industrial pollutants nitrogen oxide, power plant residual oil fly ash, and organochlorine pollutants(4). Another effect of mercury and toxic metals is a reduction in B- lymphocytes (37,38,22). One of these studies(37) dealing with autistic patients and further work with such patients has found this causes a tendency to be more seriously affected by viruses and to develop intestinal disorders including leaky gut, lymphoid modular hyperplasia, and a high incidence of parasites. Allergic contact eczema is the most frequent occupational disease(1,22), and the most common cause of contact eczema is exposure to toxic metals(1, 6- 12,22). The metals most commonly causing allergic immune reactivity are nickel, mercury, chromium, cobalt, and palladium(1,6-14,22). The highest level of sensitization is to Infants, who are most reactive to thimerosal, a form of mercury that has been used as a preservative in vaccines and eye drops(6,7). There is strong suggestive and clinical evidence for a connection between toxic metals and autism(2b,15-40).