The Detoxx™ System: Detoxification of Biotoxins in Chronic Neurotoxic Syndromes
TOWNSEND LETTER FOR DOCTORS & PATIENTS – NOVEMBER 2002
By John Foster, M.D., Patricia Kane, Ph.D., Neal Speight, M.D.
Chronically ill individuals suffering from neurotoxin exposure impacts patients with disorders such as CFIDS, Fibromyalgia, MS, Autism, Cardiovascular Disease, Depression, Rheumatoid Arthritis, IBS, Infertility, ALS, Parkinsons, Lyme, Toxic Building Syndrome, Estuary Associated Syndrome, Psychosis, Diabetes without family Hx, Optic Neuritis, Refractory Heavy Metal Toxicity, Pulmonary Hemorrhage, and Stroke. Patients diagnosed with these chronic illnesses may be potentially classified as ‘Neurotoxic Membrane Syndrome’ (NMS) with the endothelial or the neuronal cell membrane as the target of degeneration. While hypercoagulation involves a myriad of proteins, it is ultimately a membrane event, essentially disrupting the phospholipids that structure the membrane. Agglomeration (blocked cellular exposure to blood flow/nutrients and impaired cell-to-cell communication) involves an elevation of phospholipase A2 and the consequent excessive uncoupling of eicosanoids, (predominantly Arachidonic acid) from the cell membrane causing inflammation. The agglomeration that eventually occurs is, in essence, a product of a weakened membrane, and ultimately a disturbed red cell fatty acid profile.
We have established a biomedical protocol in our clinics, The WellSpring Clinic in Wayne, PA and The Center for Wellness in Charlotte, NC for patients with neurotoxic illness. Our biomedical approach is an attempt to reach the systemic nature of these tenacious neurotoxic syndromes and provide clinically proven methods that eradicate neurotoxins. Our course of action is that of freeing the patient of pervasive symptoms of neurotoxic illness in a noninvasive manner that heals the membrane, and ultimately the body and brain.
The recent pioneering work of Ritchie Shoemaker, M.D., as communicated in his book Desperation Medicine and his peer reviewed papers (Shoemaker 2001), lends strong support to a connection between Chronic Fatigue Syndrome, Fibromyalgia, Lyme Disease, Pfiesteria infection and that of numerous Neurotoxic Syndromes.
The presentation of biotoxin exposure often parallels neurological and psychological impairment due to the interrelationship between the ENS (Enteral Nervous System) and the CNS. The biliary tree, gall bladder, and bile formation within the liver serve in the vital processes of detoxication (disposal of waste products bilirubin, heavy metals, biotoxins, xenobiotics), lipid metabolism, transport and digestion (bile acids). Abnormalities of the hepatobiliary system may involve biliary stasis whereby infectious material or biotoxins reside within the liver, biliary tree and gall bladder, as a viscous suspension in biliary sludge. Biotoxins as bacteria, viruses, parasites, spirochetes, dinoflagelletes, and fungus may be within biliary sludge often creating neurotoxins that may then impact the CNS via the ENS, or the gut (The Second Brain). The occurrence of biliary sludge may be due to prolonged fasting, low fat intake, high carbohydrate diets or exposure to pathogens. Restriction of dietary fat and the subsequent lack of bile production may impair biliary flow which would be contraindicated in attempting to clear toxicity as bile is paramount to cleansing the body and getting biotoxins and heavy metals excreted into the fecal matter.
Neurotoxins are minute compounds between 200-1000 KD (kilodaltons) that are comprised of oxygen, nitrogen and sulfate atoms arranged in such a way as to make the outside of the molecule fat loving and water hating. As such, once it enters the body, it tends to bind to structures that are rich in fat such as most of our cells, especially the liver, kidney, and brain. Neurotoxins are capable of dissolving in fatty tissue and moving through it, crossing cell membranes (transporting against a gradient, particularly with potassium) and disrupting the electrical balance of the cell itself.
As fat soluble neurotoxins move through the cells of the body from the GI tract to sinus, to lung, to eye, to muscle, to joint, to nerve, they eventually enter the liver and the bile. Once -neurotoxins bind with bile they have access to the liver; the body is then poisoned over and over again as the bile is re-circulated (first released into the intestine to digest fats, and then reabsorbed).
Neurotoxins cause damage by disrupting sodium and calcium channel receptors, attacking enzyme reactions involved in glucose production thereby disrupting energy metabolism in the cell, manufacturing renegade fatty acids as saturated very long chain, odd chain and branched chain fatty acids impairing membrane function, stimulating enzymes (PLA2) which uncouple essential fatty acids from the cell membrane and impairing the function of the nuclear receptor PPAR gamma which partially controls transcription (the conversion of instructions held in our DNA to RNA which then impacts protein production in the cell).
Heavy metals are also lipid soluble and often compound the removal of biotoxins (Aschner et al 1990, 1998; Dutzak 1991). As has been observed by many clinicians, often as the patients’ heavy metal toxicity is addressed, they are faced with the additional complication of the presence of biotoxins. Biotoxins and heavy metal exposure co-exist within the cell membrane and fatty tissue requiring consideration for both types of toxicity in regard to patient intervention. By stabilizing glutathione (GSH) we reinforce the bodies natural metallothionein markers (Nordberb and Nordberb 2000, Ebadi et al 1995, Sato et al 1995, Kerper et al 1996, Susanto et al 1998), glycoaminoglycans or GAGS (Klein 1992), methylation, sulfation, hepatic and renal function as we introduce treatment protocols for detoxication with gentle, natural modalities that unload cellular toxicity safely. GSH infusion by fast IV push has been a remarkable tool to unload the body burden of heavy metals and neurotoxins in both pediatric and adult populations, without side effects.
Renegade fats as very long chain fats (VLCFAs) that are over expressed, disrupt the membrane structure. There is a beautiful geometry to the membrane that is highly sensitive to the size of the lipid chains. The overall width of the fatty acid portion of the membrane is ~3 ½ nm which must be maintained for stability. Saturated or monounsaturated fatty acids with a length of 16 or 18 carbons and polyunsaturated fatty acids of 18 to 22 carbons are preferred to permit the structure to maintain optimal horizontal fluidity. VLCFAs that range from 20 to 26 carbons force the parallel dimensions vertically or extend across the bilayer like spikes in that marvelous fluid sea. There simply is not enough room. The distortion weakens the phosphate bonds that derive their strong attraction only as long as the phospholipids are parallel to each other on both sides of the membrane. The cell weakness is then expressed in leaky attraction to ion channels and receptors which marginalize cell cytosol fluids and electrolytes with the only option as early cell death.
To view the brain beyond its architecture as a biological orchestration of the physical and chemical constituents necessary for performance, we cannot begin to conceptualize without considering the importance of fatty acids as the human brain is 60% lipid. Dendrites and synapses are up to 80% in lipid content. Although Arachidonic acid (AA) has been given a negative association, it is the most prominent essential fatty acid in the red cell and comprises 12% of the total brain and 15.5% of the body lipid content. If AA is depleted by overdosing with marine or flax oil through competitive inhibition between the omega 6s and 3s, establishing the balance of the EFAs is profoundly impaired. Often both prostaglandin one and two series relating to omega six metabolism are compromised when flax and marine oils are overdosed or lipid intake is insufficient. When AA, the lead eicosanoid of the body, is suppressed due to excess intake of marine oils (w-3s), the balance of eicosinoid control circuitry of the body is impaired as is clearly viewed in the patient’s presentation. Arachidonic acid is preferentially wasted in states of heavy metal toxicity (Tiin and Lin, 1998) and has been observed to be sharply suppressed in RBC lipid analysis in states of heavy metal toxicity (Kane, clinical observation 1997-2002).
In either states of toxicity (biotoxins or heavy metals), there is a dramatic elevation in Phospholipase A2 (PLA2) activity (Verity et al 1994). The increases in PLA2 activity result in premature uncoupling of the essential fatty acids (EFAs) from phospholipids in the cell membrane. The promiscuous release of AA (it’s the highest concentrated HUFA in the membrane) in the presence of an over expression of PLA2 results in a severely compromised increase in inflammation. Carbohydrate consumption, as one of the most profound stimulators of PLA2, must be restricted to control the insulin response and the subsequent loss of those essential EFAs and the eventual metabolic distortion.
Phospholipids, cholesterol, cerebrosides, gangliosides and sulfatides are the lipids most predominant in the brain residing within the architectural bilayers (Bazan et al 1992). The phospholipids and their essential fatty acid components provide second messengers and signal mediators. In essence, phospholipids and their essential fatty acid components play a vital role in the cell signaling systems in the neuron. The functional behavior of neuronal membranes largely depends upon the ways in which individual phospholipids are aligned, interspersed with cholesterol, and associated with proteins. All neurotransmitters are wrapped up in phospholipid vesicles prior to their release in the synaptic cleft. The release and uptake of the neurotransmitters depends upon the realignment of the phospholipid molecules. The nature of the phospholipid is a factor in determining how much neurotransmitter or metal ion will pass out of a vesicle or be taken back in. Phospholipid re-modeling may be accomplished by supplying generous amounts of balanced lipids and catalysts via nutritional intervention and the use of intravenous Phospholipid Exchange (IV Phosphatidylcholine).
An undesirable course of events in an exposure to biotoxins is agglomeration in a hypercoagulation state. The distorted membrane with its weakened structure and almost absolute reduced fluidity is powerless to resist coagulation. A highly fluid membrane would kick off an accumulation of oxidized cholesterol; it would not permit it to attach. This is not the case when the membrane is compromised, as in much of the patient population affected with neurotoxic illness.
Hypercoagulation is predominantly a non-regulated mass of proteins disrupting function. When referencing the artery; hypercoagulation invariably involves the plasmic side of the cell and if endothelial cells of the vascular system are targeted by a toxin (virus, neurotoxin, metal, antibody, etc), restriction of blood flow ultimately results. If a neuron is targeted then signaling is disrupted. The presence of neurotoxins invariably involves PLA2, which is the “sergeant at arms” monitoring cell membrane health. A membrane disturbance (unwanted mass) would trigger PLA2, which hydrolyses the release of eicosanoids, which would then induce inflammation and call to attention the clean-up committee, i.e. macrophages.
Hypercoagulation is a restrictive agglomeration, (mass) that occurs principally on the membrane of endothelial cells blocking the flow of vital fluids, blood, bile, etc., with a high causal relationship to oxidation, and equally to toxicity, quite often neurotoxins. Oxidized LDL (Sobel et al 2000) is predominantly a membrane disturbing event agglomerating and attaching to endothelial cells, while neurotoxins can move through the lipid membrane and attack the cell itself or hide in the membrane disrupting fluidity and the energy of life.
Unhealthy bacteria have been known to colonize the liver and its biliary system. These bacteria as well as viruses, spirochetes, dinoflagellates, and the like can synthesize very long chain saturated or renegade fats (Harrington et al 1968, Carballerira et al 1998) that lead to liver toxicity, biliary congestion, impairment of prostaglandin synthesis and the release of glutathione (Ballatori et al 1990). Lipids vibrate in the cell at millions of times/second. The double bonds of the omega 6 and omega 3 lipids are the singing backbone of life expressed through their high energy level. These bonds are their vibratory song, and they absolutely carry a tune befitting every act and function in the exercise of life, providing all 70 trillion of our cells their flexible nature. When renegade fats are over represented in the cell membrane they result in off key expression, and if strong enough, may spell cellular death and apoptosis. Healing the outer leaflet of the membrane (Schachter et al 1983), comprised primarily of phosphatidylcholine, with phospholipid therapy, is one of our highest priorities in addressing chronic illness and hypercoagulation.
Our clinical approach is to first confirm that neurotoxin mediated illness could in fact be a problem for the patient via the Visual Contrast Sensitivity (VCS) test (from Stereo Optical) that isolates deficits both in the photo receptor cells and in the velocity of flow in retinal capillaries. If the patient scores poorly on this test then the evaluation may include screening for cytokine elevations followed by coagulation and red blood cell lipid testing through Johns Hopkins/interpretation through BodyBio. (For pediatric patients the Heidelberg Retinal Tomogram Flow Meter Evaluation by an ophthalmologist may be preferred).
Once neurotoxins enter the cell they move toward the nucleus turning on indirectly the production of cytokines such as TNF alpha, IL6, and IL-1Beta (Shrief and Thompson 1993, Tsukamoto 1995, Abordo et al 1997,Rajora et al 1997, Brettelal 1989, Hassen et al 1999, Davidson 2001). TNF alpha will stimulate macrophages in the body to become active. The white cells are also induced to gather in the area of cytokine (TNF alpha) release. In addition, TNF alpha induces endothelial cell adhesion. Endothelial cells which line the blood vessels of the body become “sticky“ in conjunction with the increase in white cells. The increased blood viscosity results in restricted blood flow in neurotoxic patients leading to fatigue and discomfort, and quite possibly disturbed toxic photoreceptor lipid structures that become compromised with subsequent reduction in visual performance.
The cellular impact of biotoxin and heavy metal burdens results in disturbed prostaglandin synthesis, poor cellular integrity, and decreased GSH levels (DeLeve and Kaplowitz 1990, Dentico et al 1995, Hayter et al 2001, Miles et al 2000, Nagai et al 2002, Zalups and Barfuss 1995, Watanabe et al 1988, Fernandez-Checa et al 1996), with significant suppression of omega 6 arachidonic acid, marked elevation of Renegade fats and ultimately with demyelination (depressed DMAs). The presence of VLCFAs are evidence of peroxisomal dysfunction and suppression of the beta oxidation of lipids and cellular respiration. Renegade fats (VLCFAs, Odd Chains, Branched Chains) are represented as an increase in fat content in the brain as discovered in stroke patients examined by Stanley Rapoport, Chief of the Laboratory of Neuroscience at the NIH. Biotoxins and heavy metals are lipid soluble thus the effect upon cellular processes and hepatobiliary function is often gravely deranged.
Peroxisomes, most prevalent in the liver and kidney, are organelles within the cell that play a crucial role in clearing xenobiotics and the third phase of detoxification. Peroxisomes are intimately involved in cellular lipid metabolism (Bentley et al 1993, Mannaerts and Van Veldhoven 1992, Luers et al 1990, Leiper 1995) as in the biosynthesis of fatty acids via ß-oxidation involving physiologically important substrates for thromboxanes, leukotrienes and prostaglandins. The creation of a prostaglandin is an oxidative event (Diczfalusy 1994). Inappropriate use of antioxidants (mega-dosing) will inhibit ß-oxidation, the production of prostaglandins and cellular metabolism, thus the liberal use of potent antioxidants might be contraindicated in the buildup of Renegade fats (Akasaka et al 2000) which are the hallmark of toxicity (Kane and Kane 1997, Kane 1999, Kane 2000, Roels et al 1993, Rustan et al 1992). Peroxisomal oxidation enzymes are suppressed by elevation of cytokines such as TNFalpha (Beier et al 1992).
Individuals with immune, CNS, cardiac, GI and endocrine disorders often present with complex xenobiotics involving disturbances in the cytochrome P450 superfamily (hepatic detoxification difficulties) which parallels disturbances in peroxisomal function. The cytochrome P450’s are responsible for the biotransformation of endogenous compounds including fatty acids, steroids, prostaglandins, leukotrienes and vitamins as well as the detoxification of exogenous compounds resulting in substantial alterations of P450s (Guengerich 1991) as xenobiotics may turn off or greatly reduce the expression of constitutive isoenzymes (Sharma et al 1988). Inadequate stores of arachidonic acid can compromise P450 function (McGiff 1991). Oral application of hormones such as pregnenolone, DHEA (Di Santo et al 1996, Ram et al 1994, Rao et al 1993) or thyroid stimulate peroxisomal proliferation and the ß-oxidation of Renegade fats as would nutrients (riboflavin, pyruvate, manganese) and oxidative therapies. Anti-oxidants slow cellular metabolism and must remain in the proper balance with all the essential nutrients and substrates (lipids, protein) to maintain metabolic equilibrium. Removal of renegade fats in the diet is accomplished by the avoidance of mustard, canola oil (Naito et al 2000), peanuts and peanut oil which contain VLCFAs that can challenge patients with liver and CNS toxicity. The oral use of butyrate, a short 4-carbon chain fatty acid, is of striking benefit (Fusunyan et al 1998, Segain et al 1983, Yin et al 2001) in mobilizing renegade fats, lowering TNFalpha, sequestering ammonia, and clearing biotoxins.
In states of toxicity it is paramount to stabilize omega 6 fatty acids and the lead eicosanoid (Attwell et al 1993) Arachidonic acid (AA) before introducing omega 3 lipids. There exists a crucial balance between omega 6 and omega 3 fatty acids in human lipid metabolism which has only recently been brought into clearer focus through the work of Yehuda (1993, 1994, 1995, 1998, 2000, 2002). His extensive research has revealed that the optimum ratio is 4:1 of omega 6 to omega 3 FAs. AA, the lead eicosanoid, as well as the other w6 EFAs must be stable (in sufficient amounts) before w3 fatty acids are introduced. Clinicians are often met with poor patient outcomes when merely administering omega 3 lipids without first checking on the omega 6 fatty acid content. Low w6s call for dietary additions of animal protein as eggs, butter and meat, which then permit the addition of controlled addition of w3s. The preferred marine oils are generally those higher in EPA and lower in DHA (EPA:DHA), such as Kirunol 3:1, Nordic Naturals 4.5:1, or Omega Brite 7:1). The fear of w6s has been grossly overemphasized by focusing on AA and inflammation. It is true that our modern diet is currently flooded with w6 oils. However, there is currently an over expression of marine oils in a majority of our patients that easily distorts the balance of w6s and w3s with the subsequent suppression in many patients of the all important w6s. We see this distortion daily through the examination of their lipid profiles from Johns Hopkins U. The solution lies in dietary control of carbohydrates which directly lowers PLA2 and inflammation, and the correct administration of a true balance of w6s and w3s with adequate testing information. The balance of lipids is far too important for guesswork, we must be more precise before we can impact toxic body syndromes.
The body loses its ability to metabolize fats in states of toxicity and therefore becomes depleted in the eicosanoids and prostaglandins. Essential fatty acids are the precursors to the regulatory prostaglandins which are “local hormones” providing the communication controlling all cell to cell interactions. An optimum balance of fatty acids make up the dynamic membrane. The membrane of every living cell and organelle is composed of two fatty acid tails facing each other. This bilipid layer is so minute (3.5 nanometers) that it would take 10,000 membranes layered on top of each other to make up the thickness of this paper. Yet the dynamics that occur within this tiny envelope is a microcosm that is a challenge for the human mind to envision. Mercury toxicity damages the microtubule structure of the cell, actually dissolves them (Boyd Hailey, lecture 1997). All cells must synthesize molecules and expel waste. All cells must create, through gene expression, the proteins needed for cellular gates embedded in the membrane as ion channels and receptors. The ultimate control of how those peptides behave rests with the high degree of fluidity and the balance of omega 6, omega 3 lipds in the membrane, while the strength of the membrane rests with the structural fats (oleic, stearic, palmitic, cholesterol). Without control of membrane function through lipid manipulation, detoxication is compromised. In essence, the life of the cell is intimately tied to the health of the membrane and the health of the entire organism.
Our clinical protocol at the WellSpring Clinic in Wayne, PA is to initiate treatment with changing the patients’ overall diet, addressing the lipid balance and especially the outer lipid leaflet of the cell membrane through fatty acid therapy and the addition of supplementation targeted towards dissolving fibrin, clearing the liver/biliary tree, and healing the cell membrane. Patient progress is evaluated through the Visual Contrast Test and lab evaluation.
Blood thinning agents such as Heparin and Warfarin increase blood flow around the blocked endothelium, however, reconstituting membrane fluidity can directly address coagulation in a natural restorative way. Vibrant healthy membranes will not permit agglomeration. The high polyunsaturated lipids with a preponderance of phosphatidylcholine on the plasmic surface precludes undesirable clumping to occur. Treatment modalities, however, could address both, dissolving fibrin and healing the cell membrane.
It has been suggested that the use of heparin will address hypercoagulation. Recent data from JAMA (Stephenson 2001) indicates that the use of low dose heparin may transform a ‘benign fungal infection into a toxic shock-like reaction’. This research was presented at the 39th annual meeting of the Infectious Diseases Society of America in 2001 by Margaret K. Hostetter, M.D. of Yale University School of Medicine (Hostetter 2001 and San-Blas et al 2000). Hostetter and colleagues found that Candida albicans can attach to host cells and form invasive hyphae. Low dose heparin utilized in procedures for hospitalized patients through the practice of heparin in intravascular catheters may transform C. albicans into a life-threatening pathogen. Hostetter was able to identify a gene, INT1, encoding a C. albicans surface protein, Intlp, which was linked with adhesion, the ability to grow filaments and ultimately virulence of C. albicans of a systemic nature. The use of heparin raises the cytokines TNF alpha and IL-6 (Stephenson 2001) in addition to PLA2 (Mudher et al 1999; Kern et al 2000; Farooqui 1999; Verity et al 1994). Biotoxins which form neurotoxins, may create a state of hypercoagulation from the rise in TNF alpha. Consequently, the use of heparin may exacerbate the hypercoagulation and the neurotoxic condition. The source of the problem–biotoxins, which have formed neurotoxins creating a state of hypercoagulation, must be addressed from the context of healing the cell membrane.
By stabilizing lipid status with intravenous Phospholipid exchange and oral EFA supplementation we have remarkable tools to unload the body burden of neurotoxins (Jenkins et al 1982, Cariso et al 1983, Jaeschke et al 1987, Kolde et al 1992) in both pediatric and adult populations, without side effects. Oral use of phospholipids in a Liver Flush is also an effective intervention in addressing neurotoxic syndromes.
Through isolating individual fatty acids in red cells we can now examine the cellular integrity/structure, fluidity, the formation of renegade fats that impair membrane function, and the intricate circuitry of the prostaglandins. The systemic health of the individual patient may be reached and targeted nourishment utilized through evidence based intervention which may yield positive patient outcomes. Healing the membrane is virtually.…..healing the brain.
Neal Speight, M.D. may be reached at Center For Wellness in Charlotte, NC. Contact John Foster, M.D. and Patricia Kane, Ph.D. at the WellSpring Clinic in Wayne, PA to obtain the ‘The Detoxx Book: Detoxification of Biotoxins in Chronic Neurotoxic Syndromes’ at 888.320.8338 or 856.825.8338
* BodyBio performs thousands of Fatty Acid laboratory analysis yearly for physicians around the world and conducts FA lecture courses.
** Cottonseed oil is usually grown with high pesticides and herbicides. Oil is a byproduct. Best to avoid.
Mudher AK et al Heparin injection into the adult rat hippocampus induces seizures in the absence of macroscopic abnormalities Neuroscience 89:2:329-333, Mar 1, 1999
Nagai H, Matsumaru K, Feng G, Kaplowitz N Reduced glutathione depletion causes necrosis and sensitization to tumor necrosis factor-alpha-induced apoptosis in cultured mouse hepatocytes Hepatology 36(1):55-64, Jul 2002
Naito Y, Konishi C, Ohora N Blood Coagulation and Osmolar Tolerance of Erythrocytes in Stroke-Prone spontaneously Hypertensive rats given rapeseed oil or soybean oil as the only dietary fat Toxicology Letters 116:3:209-215, 2000
Nelson GJ, Schmidt PC, Bartonlini G, Kelley DS, Kyle D The effect of dietary Arachidonic acid on Platelet function, Platelet Fatty Acid composition, and Blood Coagulation in Humans Lipids 32:4:421-425, Apr 1997
Nordberb M, Nordberb GF Toxicological Aspects of Metallothionein Cellular & Molecular Biology 46:2:March 2000
Rajora N, Boccoli G, Burns D, Sharma S, Catania AP, Lipton JM alpha-MSH modulates local and circulating Tumor Necrosis Factor alpha in experimental Brain Inflammation J Neurosci 17:6:2181-, Mar 15, 1997
Ram PA, Waxman DJ DHEA 3 ß-sulfate is an Endogenous activator of the Peroxisome-Proliferation Pathway: Induction of Cytochrome P450 4A and Acyl-Co oxidase mRNAs in Primary rat Hepatocyte culture and Inhibitory effects of Ca++ Channel Blockers Biochem J 301:753-758, 1994
Rao MS, Ide H, Alveres K et al Comparative effects of DHEA and related Steroids on Peroxisome Proliferation in rat liver Life Sci 52:1709-1716,1993
Roels F, Espeel M, Poggi F, Mandel H, Van Maldergem L, Saudubray JM Human Liver Pathology in Peroxisomal Diseases: A Review including Novel Data Biochimie 75:281-292,1993
Rustan AC, Christiansen EN, Drevon AC Serum lipids, Hepatic Glycerolipid Metabolism and Peroxisomal fatty acid oxidation in rats fed omega-3 and omega-6 fatty acids Biochem J 283:333-339,1992
San-Blas G et al Fungal morphogenesis and virulence Med Mycol 38 Suppl 1:79-86, 2000
Sato M et al Induction of Metallothionein Synthesis by Glutathione depletion after trans- and cis-stilbene oxide administration in rats Chemico-Biological Interactions 98:15-25, 1995
Schachter D, Abbott RE, Cogan U, Flamm M Lipid Fluidity of the individual hemileaflets in human erythrocyte membranes Ann N Y Acad Sci 414:19-28, 1983
Sharma R, Lake BG, Foster J, Gibson GG Microsomal Cytochrome P452 Induction & Peroxisomal Proliferation by Hypolipidaemic Agents in Rat Liver: A Mechanistic Inter-Relationship Biochem Pharm 37:1193-1201, 1988
Segain JP, Bletiere DR, Bourreille A, Leray V, Gervois N, Rosales C, Ferrier L, Bonnet C, Blottiere HM, Galmiche JP Butyrate inhibits Inflammatory responses through NFkB inhibition: Implications for Crohn’s Disease Gut 47:397-403, 2000
Shoemaker, RC Residential and recreational acquisition of possible estuary associated syndrome – a new approach to successful diagnosis and treatment, Environmental Health Perspectives 109-Suppl 5:791-6, Oct 2001
Shoemaker, RC Desperation Medicine Gateway Press: Baltimore, MD, 2001
Shrief MK, Thompson EJ In vivo relationship of TNF-alpha to BBB damage in patients with active MS
J Neuroimmunol 38:27-34, 1993
Sobal G, Menzel J, Sinzinger H Why is glycated LDL more sensitive to Oxidation than Native LDL? A comparative study Prostaglandins, Leukotrienes and Essential Fatty Acids 63:4:177-186, 2000
Stephenson J Can a Common Medical Practice Transform Candida Infections
from Benign to Deadly? JAMA 286:20: Nov 28, 2001
Susanto I, Wright SE, Lawson RS, Williams CE, Deneke SM Metallothionein, glutathione, and cystine transport in pulmonary artery endothelial cells and NIH/3T3 cells Am J Physiol 274(2 Pt 1):L296-300, Feb 1998
Tiin SJ, Lin TH Effects of Metallic Antioxidants on Cadmium-catalyzed Peroxidation of Arachidonic Acid Annals of Clin and Lab Sci 28:1:43-50, 1998
Tsukamoto T, Ishikawa M, Yamamoto T Suppressive effects of TNF-alpha on Myelin formation in vitro Acta Neurol Scan 91:1:71-5, Jan 1995
Verity MA, Sarafian T, Pacifici EHK, Seranian A Phospholipase A2 Stimulation by Methyl Mercury in Neuron culture J of Neurochem 62:705-714, 1994
Watanabe H, Shimojo N, Sano K, Yamaguchi S The Distribution of Total Mercury in the Brain after the lateral ventricular singe injection of Methylmercury and Glutathione Res Comm Chem Path Pharm 60:1, April 1988
Yehuda S, Carasso RL Modulation of learning pain thresholds, and thermoregulation in the rat by preparations of free-purified alpha linolenic and linoleic acids: determination of the optimal w3-to-w6 ratio Proc Natl Acad Sci USA 90:10345-10349, 1993
Yehuda S, Carasso RL, Motofsky DI Essential fatty acid preparation (SR-3) raises the seizure threshold in rats Eur J Pharmacol 254:193-198, 1994
Yehuda S, Carasso RL, Motofsky DI Essential fatty acid preparation (SR-3) rehabilitates learning deficits induced by AF64A and 5,7-DHT NeuroReport 6:511-515, 1995
Yehuda S, Rabinovitz S, Mostofsky DI Effects of essential fatty acid preparation (SR-3) on brain lipids, biochemistry and behavioral and cognitive functions. In: Yehuda A, Mostofsky DI Eds. Handbook of essential fatty acid biology, biochemistry physiology, and behavioral neurobiology New York: Humana Press 427-452, 1997
Yehuda S, Rabinovitz S, Mostofsky DI Modulation of learning and neuronal membrane composition in the rat by essential fatty acid preparation: time-course analysis Neurochem Res 23:5:627-34, May 1998
Yehuda S, Rabinovitz S, Mostofsky DI Essential fatty acids and sleep: mini review and hypothesis Med Hypothesis 50:2:139-45, Feb 1998
Yehuda S, Rabinovitz S, Carasso RL, Mostofsky DI Fatty acids and Brain Peptides Peptide 19:2:407-419, 1998
Yehuda S, Rabinovitz S, Carasso RL, Mostofsky DI Fatty acid mixture counters stress changes in cortisol, cholesterol, and impair learning Int J Neurosci 101:1-4:73-87, 2000
Yehuda S Possible anti-Parkinson properties of N-(alpha-linolenoyl) tyrosine. A new molecule.
Pharmacol Biochem Behav 72:1-2:7-11, May 2002
Zachowski A Phospholipids in Animal Eukaryotic Membranes: Transverse Asymmetry and Movement Biochem J 294:1-14, 1993
Zeisel SH Choline: an essential nutrient for humans Nutrition 16(7-8):669-71, Jul-Aug, 2000
Zhang JY, Prakash C, Yamashita K, Blair IA Regiospecific and Enantioselective Metabolism of 8,9-Epoxyeicosatrienoic Acid by Cycooxygenase Biochem and Biophys Research Com 183:1:138-143,1992
Zierenberg O, Betzing H Pharmacokinetics and metabolism of IM injected polyenyl phosphatidylcholine liposomes Arzneimittelforschung 29:3:494-8, 1979
Yin L, Laevsky G, Giardina C Butyrate suppression of colonocyte NF-kappa B activation and cellular proteasome activity J Biol Chem276(48):44641-6, Nov 2001
Zalups RK, Barfuss DW Accumulation and Handling of Inorganic Mercury in the Kidney after Coadministration with Glutathione J Toxicol Environ Health 44:385-399, 1995
1258 Mann Drive
Matthews, NC 28105
9am - 5pm