{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:16:34Z","timestamp":1773321394314,"version":"3.50.1"},"reference-count":122,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T00:00:00Z","timestamp":1352332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Entropy"],"abstract":"<jats:p>In a recent paper, we proposed that a contributing factor in autism is a deficiency in cholesterol sulfate supply. In this paper, we investigate a link between preeclampsia and subsequent autism in the child, and we hypothesize that both conditions can be attributed to a severe depletion of cholesterol sulfate. Through studies on the Vaccine Adverse Event Reporting System (VAERS) database, we demonstrate a strong statistical relationship among the signs and symptoms associated with autism and those associated with preeclampsia, pernicious anemia, and serious adverse reactions to vaccines. We show that VAERS reports associated with symptoms typical of pernicious anemia produce both a set of symptoms that are highly correlated with preeclampsia and another set highly correlated with autism. We explain this observation via an argument that, in a severe reaction, the cascade of events subsequent to vaccination reflects a profuse production of nitric oxide (NO) and consequential destruction of both red blood cells (RBCs) and cobalamin. This may explain the diverse signs and symptoms associated with both preeclampsia and severe vaccine adverse reactions. We argue that excess NO synthesis, induced by the aluminum and antigen in vaccines, results in hemolysis of RBCs, which allows hemoglobin to scavenge the excess NO, converting it to nitrate. The NO is also scavenged by cobalamin, leading to its inactivation and contributing to subsequent pernicious anemia. Finally, we demonstrate that severe adverse reactions to vaccines can be associated with life-threatening conditions related to the heart and brain, as well as stillbirth, when the vaccine is administered to a woman in the third-trimester of pregnancy, as demonstrated by statistical analysis of the Gardasil records.<\/jats:p>","DOI":"10.3390\/e14112265","type":"journal-article","created":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T11:04:29Z","timestamp":1352372669000},"page":"2265-2290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Is Cholesterol Sulfate Deficiency a Common Factor in Preeclampsia, Autism, and Pernicious Anemia?"],"prefix":"10.3390","volume":"14","author":[{"given":"Stephanie","family":"Seneff","sequence":"first","affiliation":[{"name":"Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Davidson","sequence":"additional","affiliation":[{"name":"Internal Medicine Group Practice, PhyNet, Inc., Longview, TX 75604, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2012,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"ACOG Committee on Practice Bulletins\u2013Obstetrics (2002). ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia, Number 33. Obstet. Gynecol., 99, 159\u2013167.","DOI":"10.1097\/00006250-200201000-00028"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/0002-9378(89)90665-0","article-title":"Preeclampsia: An endothelial cell disorder","volume":"161","author":"Roberts","year":"1989","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1067\/mob.2002.123895","article-title":"Abnormal iron parameters in the pregnancy syndrome preeclampsia","volume":"187","author":"Rayman","year":"2002","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1007\/s10803-009-0903-4","article-title":"Pre-eclampsia, birth weight, and autism spectrum disorders","volume":"40","author":"Mann","year":"2010","journal-title":"J. Autism Dev. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.mehy.2011.10.026","article-title":"Might cholesterol sulfate deficiency contribute to the development of autistic spectrum disorder?","volume":"8","author":"Seneff","year":"2012","journal-title":"Med. Hypotheses"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1046\/j.1523-1755.2000.00858.x","article-title":"Glomerular heparan sulfate alterations: Mechanisms and relevance for proteinuria","volume":"57","author":"Raats","year":"2000","journal-title":"Kidney Int."},{"key":"ref_7","first-page":"875","article-title":"Elevated plasma total homocysteine in preeclampsia","volume":"29","author":"Hasanzadeh","year":"2008","journal-title":"Saudi Med. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00404-006-0223-2","article-title":"Homocysteine, folic acid and B12 serum levels in pregnancy complicated with preeclampsia","volume":"275","author":"Makedos","year":"2007","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s12291-011-0109-3","article-title":"Study of serum homocysteine, folic acid and vitamin B12 in patients with preeclampsia","volume":"26","author":"Mujawar","year":"2011","journal-title":"Ind. J. Clin. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/0891-5849(93)90151-J","article-title":"Homocysteine metabolism and the oxidative modification of proteins and lipids","volume":"14","author":"Olszewski","year":"1993","journal-title":"Free Radic. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1056\/NEJM199711133372007","article-title":"Pernicious Anemia","volume":"337","author":"Toh","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1194\/jlr.R300005-JLR200","article-title":"Cholesterol Sulfate in human physiology: What\u2019s it all about?","volume":"44","author":"Strott","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0378-4347(97)00450-7","article-title":"Alteration of acidic lipids in human sera during the course of pregnancy: Characteristic increase in the concentration of cholesterol sulfate","volume":"704","author":"Lin","year":"1997","journal-title":"J. Chromatogr. B"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1172\/JCI102247","article-title":"Surface effects on blood-clotting components as determined by zeta potentials","volume":"29","author":"Horan","year":"1950","journal-title":"J. Clin. Invest."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12404","DOI":"10.1016\/S0021-9258(19)38361-9","article-title":"Cholesterol sulfate inhibits the fusion of Sendai virus to biological and model membranes","volume":"265","author":"Cheetham","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0005-2736(74)90174-6","article-title":"Cholesterol sulfate. I. Occurrence and possible biological function as an amphipathic lipid in the membrane of the human erythrocyte","volume":"352","author":"Bleau","year":"1974","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1161\/01.CIR.0000108925.95658.8D","article-title":"Expression of cholesterol sulfotransferase (SULT2B1b) in human platelets","volume":"109","author":"Yanai","year":"2004","journal-title":"Circulation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s004030050316","article-title":"Expression of nitric oxide synthase III (eNOS) mRNA by human skin cells: Melanocytes but not keratinocytes express eNOS mRNA","volume":"290","author":"Jackson","year":"1998","journal-title":"Arch. Dermatol. Res."},{"key":"ref_19","first-page":"614","article-title":"Heparin inhibition of anaphylactic shock","volume":"7","author":"Hyde","year":"1927","journal-title":"J. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15583","DOI":"10.1074\/jbc.272.25.15583","article-title":"Reciprocal regulation of endothelial nitric-oxide synthase by Ca2+-calmodulin and caveolin","volume":"272","author":"Michel","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1136\/heart.85.3.342","article-title":"Endothelial function and nitric oxide: Clinical relevance","volume":"85","author":"Vallance","year":"2001","journal-title":"Heart"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10341","DOI":"10.1073\/pnas.152149699","article-title":"Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions","volume":"99","author":"Joshi","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/nbt0798-672","article-title":"Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin","volume":"16","author":"Doherty","year":"1998","journal-title":"Nat. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1038\/327524a0","article-title":"Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor","volume":"327","author":"Palmer","year":"1987","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1021\/bi992040p","article-title":"Rate of deactivation of nitric oxide-stimulated soluble guanylate cyclase: Influence of nitric oxide scavengers and calcium","volume":"39","author":"Margulis","year":"2000","journal-title":"Biochemistry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"39024","DOI":"10.1074\/jbc.M509045200","article-title":"Nitric oxide scavenging by red blood cells as a function of hematocrit and oxygenation","volume":"280","author":"Azarov","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1097\/00003072-199204000-00014","article-title":"Diagnosis by radiocolloid imaging of postpartum hepatic necrosis in the syndrome of hemolysis, elevated liver enzymes, and low platelets","volume":"17","author":"Davidson","year":"1992","journal-title":"Clin. Nucl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1001\/archinte.1965.03870010085011","article-title":"Diseases of hypersensitivity: Disseminated intravascular coagulation","volume":"116","author":"McKay","year":"1965","journal-title":"Arch. Intern. Med."},{"key":"ref_29","first-page":"186","article-title":"Progress in disseminated intravascular coagulation","volume":"111","author":"McKay","year":"1969","journal-title":"Calif. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1172\/JCI107599","article-title":"Stimulation of heme oxygenase in macrophages and liver by endotoxin","volume":"53","author":"Gemsa","year":"1974","journal-title":"J. Clin. Invest."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/SHK.0b013e3181834115","article-title":"Heme oxygenase-1 induction in macrophages by a hemoglobin-based oxygen carrier reduces endotoxin-stimulated cytokine secretion","volume":"31","author":"Roach","year":"2009","journal-title":"Shock"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1378\/chest.122.3.1061","article-title":"Catastrophic cardiovascular adverse reactions to protamine are nitric oxide\/cyclic guanosine monophosphate dependent and endothelium mediated: Should methylene blue be the treatment of choice?","volume":"122","author":"Viaro","year":"2002","journal-title":"Chest"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1172\/JCI25426","article-title":"Anaphylactic shock depends on PI3K and eNOS-derived NO","volume":"116","author":"Cauwels","year":"2006","journal-title":"J. Clin. Invest."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.3390\/e14081399","article-title":"The initial common pathway of inflammation, disease, and sudden death","volume":"14","author":"Davidson","year":"2012","journal-title":"Entropy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1021\/jp909034c","article-title":"Can salting-in\/salting-out ions be classified as chaotropes\/kosmotropes?","volume":"114","author":"Zangi","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4356","DOI":"10.1016\/S0043-1354(02)00137-9","article-title":"Solubility controls on aluminum in drinking water at relatively low and high pH","volume":"36","author":"Kvech","year":"2002","journal-title":"Water Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1046\/j.1440-1711.1998.00760.x","article-title":"Antigen-specific lymphocytes enhance nitric oxide production in Mycobacterium bovis BCG-infected bovine macrophages","volume":"76","author":"Carpenter","year":"1998","journal-title":"Immunol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6627","DOI":"10.1074\/jbc.M110.167247","article-title":"Intraphagosomal peroxynitrite as a macrophage-derived cytotoxin against internalized Trypanosoma cruzi: Consequences for oxidative killing and role of microbial peroxiredoxins in infectivity","volume":"286","author":"Alvarez","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/gm228","article-title":"Gut microbiome-host interactions in health and disease","volume":"3","author":"Kinross","year":"2011","journal-title":"Genome Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1099\/jmm.0.46101-0","article-title":"Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children","volume":"54","author":"Parracho","year":"2005","journal-title":"J. Med. Microbiol."},{"key":"ref_41","unstructured":"Oller, J.W., Oller, S.D., and Oller, S.N. (2010). Autism: The Diagnosis, Treatment, & Etiology of the Undeniable Epidemic, Jones & Bartlett Learning."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1177\/1362361303007002004","article-title":"Prevalence of chronic gastrointestinal symptoms in children with autism and autistic spectrum disorders","volume":"7","author":"Molloy","year":"2003","journal-title":"Autism"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1177\/088307380001500701","article-title":"Short-term benefit from oral vancomycin treatment of regressive-onset Autism","volume":"15","author":"Sandler","year":"2000","journal-title":"J. Child Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.anaerobe.2011.03.007","article-title":"State of the art; Microbiology in health and disease. Intestinal bacterial flora in autism","volume":"17","author":"Finegold","year":"2011","journal-title":"Anaerobe"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1365-2672.1988.tb01891.x","article-title":"Competition for hydrogen between sulphate-reducing bacteria and methanogenic bacteria from the human large intestine","volume":"65","author":"Gibson","year":"1988","journal-title":"J. Applied Bacteriol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1128\/aem.54.11.2750-2755.1988","article-title":"Use of a three-stage continuous culture system to study the effect of mucin on dissimilatory sulfate reduction and methano-genesis by mixed populations of human gut bacteria","volume":"54","author":"Gibson","year":"1988","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_47","first-page":"34","article-title":"Nitric oxide and inflammatory bowel disease: Evidence for local intestinal production in children with active colonic disease","volume":"26","author":"Levine","year":"1998","journal-title":"J. Pediatr. Gastr. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1574-6968.1991.tb04799.x","article-title":"Growth and activities of sulphate-reducing bacteria in gut contents of healthy subjects and patients with ulcerative colitis","volume":"86","author":"Gibson","year":"1991","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.biopsych.2003.09.001","article-title":"High nitric oxide production in autistic disorder: A possible role for interferon-\u03b3","volume":"55","author":"Sweeten","year":"2004","journal-title":"Biol. Psychiat."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0009-8981(03)00119-0","article-title":"Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism","volume":"331","author":"Zoroglu","year":"2003","journal-title":"Clin. Chim. Acta"},{"key":"ref_51","first-page":"377","article-title":"Nitric Oxide as a Physiopathological Factor in Neuropsychiatric Disorders","volume":"18","author":"Akyol","year":"2004","journal-title":"In Vivo"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/cbf.989","article-title":"Pathophysiological role of nitric oxide and adrenomedullin in autism","volume":"21","author":"Zoroglu","year":"2003","journal-title":"Cell Biochem. Funct."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/0140-6736(93)90485-Y","article-title":"Disruption of sulphated glycosaminoglycans in intestinal inflammation","volume":"341","author":"Murch","year":"1993","journal-title":"The Lancet"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.anaerobe.2011.12.018","article-title":"Microbiology of regressive autism","volume":"18","author":"Finegold","year":"2012","journal-title":"Anaerobe"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/JCP.0b013e3181845f48","article-title":"Autism, gut\u2013blood\u2013brain barrier, and mast cells","volume":"2","author":"Theoharides","year":"2008","journal-title":"J. Clin. Psychopharm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.neulet.2010.01.033","article-title":"Low-grade endotoxemia in patients with severe autism","volume":"471","author":"Emanuele","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.1210\/jc.2004-2210","article-title":"Preeclampsia is associated with impaired regulation of the placental nitric oxide-cyclic guanosine monophosphate pathway by corticotropin-releasing hormone (CRH) and CRH-related peptides","volume":"90","author":"Karteris","year":"2005","journal-title":"J. Clin. Endocrin. Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1074\/jbc.272.2.1026","article-title":"Role of multidrug resistance P-glycoproteins in cholesterol esterification","volume":"272","author":"Debry","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0163-7827(01)00009-1","article-title":"Do sterols reduce proton and sodium leaks through lipid bilayers?","volume":"40","author":"Haines","year":"2001","journal-title":"Prog. Lipid Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0079-6107(02)00053-6","article-title":"Physiological and pathophysiological roles of ATP-sensitive K+ channels","volume":"81","author":"Seino","year":"2003","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/305147a0","article-title":"ATP-regulated K+ channels in cardiac muscle","volume":"305","author":"Noma","year":"1983","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"C3","DOI":"10.1152\/ajpcell.1990.259.1.C3","article-title":"Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone","volume":"259","author":"Nelson","year":"1990","journal-title":"Am. J. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.1016\/j.fertnstert.2008.05.019","article-title":"The influence of progesterone on endometrial nitric oxide synthase expression","volume":"91","author":"Khorram","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/S0006-2952(01)00936-4","article-title":"Lack of involvement of extracellular signal- regulated kinase (ERK) in the agonist-induced endothelial nitric oxide synthesis","volume":"63","author":"Schmidt","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_65","first-page":"501","article-title":"Fetal cells and cell-free fetal DNA in maternal blood: New insights into pre-eclampsia","volume":"8","author":"Hahn","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1067\/mob.2001.109594","article-title":"Elevation of both maternal and fetal extracellular circulating deoxyribonucleic acid concentrations in the plasma of pregnant women with preeclampsia","volume":"184","author":"Zhong","year":"2001","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1053\/plac.2000.0560","article-title":"Placental debris, oxidative stress and pre-eclampsia","volume":"21","author":"Redman","year":"2000","journal-title":"Placenta"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S1297-9589(01)00180-1","article-title":"The pathogenesis of pre-eclampsia","volume":"29","author":"Redman","year":"2001","journal-title":"Gynecol. Obstet. Fertil."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1176\/appi.ajp.2011.11091447","article-title":"Differences in white matter fiber tract development present from 6 to 24 months in infants with autism","volume":"169","author":"Wolff","year":"2012","journal-title":"Am. J. Psychiatry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0306-4522(01)00447-X","article-title":"Nitric oxide toxicity in CNS white matter: An in vitro study using rat optic nerve","volume":"109","author":"Garthwaite","year":"2002","journal-title":"Neuroscience"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1124\/mol.61.1.97","article-title":"Soluble guanylyl cyclase activator YC-1 protects white matter axons from nitric oxide toxicity and metabolic stress, probably through Na+ channel inhibition","volume":"61","author":"Garthwaite","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/00004583-199001000-00020","article-title":"Seizure disorders in autism","volume":"29","author":"Volkmar","year":"1990","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/S0006-8993(03)03034-8","article-title":"Prevention of kainic acid seizures-induced changes in levels of nitric oxide and high-energy phosphates by 7-nitroindazole in rat brain regions","volume":"981","author":"Gupta","year":"2003","journal-title":"Brain Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.eplepsyres.2005.05.001","article-title":"Sequential changes of nitric oxide levels in the temporal lobes of kainic acid-treated mice following application of nitric oxide synthase inhibitors and phenobarbital","volume":"65","author":"Kato","year":"2005","journal-title":"Epilepsy Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"8565","DOI":"10.1523\/JNEUROSCI.5698-08.2009","article-title":"Endogenous nitric oxide is a key promoting factor for initiation of seizure-like events in hippocampal and entorhinal cortex slices","volume":"29","author":"Kovacs","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/S0005-2728(00)00238-3","article-title":"Regulation of mitochondrial respiration by nitric oxide inhibition of cy- tochrome c oxidase","volume":"1504","author":"Brown","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.bbabio.2004.03.016","article-title":"Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols","volume":"1658","author":"Brown","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/1531-8249(200011)48:5<766::AID-ANA10>3.0.CO;2-M","article-title":"Mitochondrial complex I deficiency in the epileptic focus of patients with temporal lobe epilepsy","volume":"48","author":"Kunz","year":"2000","journal-title":"Ann. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1093\/brain\/awh568","article-title":"Metabolic dysfunction during neuronal activation in the ex vivo hippocampus from chronic epileptic rats and humans","volume":"128","author":"Kann","year":"2005","journal-title":"Brain"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1016\/j.freeradbiomed.2004.08.021","article-title":"Mitochondrial dysfunction and oxidative stress: Cause and consequence of epileptic seizures","volume":"37","author":"Patel","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3844\/ajbbsp.2008.208.217","article-title":"Evidence of mitochondrial dysfunction in autism and implications for treatment","volume":"4","author":"Rossignol","year":"2008","journal-title":"Am. J. Biochem. Biotech."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.1016\/j.vaccine.2004.03.032","article-title":"Aluminium adjuvants-in retrospect and prospect","volume":"22","author":"Lindblad","year":"2004","journal-title":"Vaccine"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1016\/j.vaccine.2009.01.084","article-title":"Mechanism of action of licensed vaccine adjuvants","volume":"27","author":"Tritto","year":"2009","journal-title":"Vaccine"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"148","DOI":"10.4236\/wjv.2011.14015","article-title":"Uric acid: A possible mediator of the adjuvant effect of alum in mice immunized with ovalbumin","volume":"1","author":"Chakhtoura","year":"2011","journal-title":"WJV"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1084\/jem.20071087","article-title":"Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells","volume":"205","author":"Kool","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/nature01991","article-title":"Molecular identification of a danger signal that alerts the immune system to dying cells","volume":"425","author":"Shi","year":"2003","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/MAJ.0b013e31817727af","article-title":"Uric acid directly promotes human T-cell activation","volume":"337","author":"Webb","year":"2009","journal-title":"Am. J. Med. Sci."},{"key":"ref_88","first-page":"38","article-title":"Toxic metals and essential elements in hair and severity of symptoms among children with autism","volume":"7","author":"Amin","year":"2012","journal-title":"Maedica"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1042\/CS20120130","article-title":"Toll-like receptor 9 activation: a novel mechanism linking placenta-derived mitochondrial DNA and vascular dysfunction in pre-eclampsia","volume":"123","author":"Goulopoulou","year":"2012","journal-title":"Clin. Sci. (Lond.)"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/90609","article-title":"Toll-like receptors: Critical proteins linking innate and acquired immunity","volume":"2","author":"Akira","year":"2001","journal-title":"Nature Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.2174\/092986711795933740","article-title":"Aluminum vaccine adjuvants: Are they safe?","volume":"18","author":"Tomljenovic","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.mehy.2008.09.040","article-title":"A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome","volume":"72","author":"Exley","year":"2009","journal-title":"Med. Hypotheses"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"M. Kawahara, M., and Kato-Negishi, M. (2011). Link between aluminum and the pathogenesis of Alzheimer\u2019s disease: The integration of the aluminum and amyloid cascade hypotheses. Int. J. Alzheimers Dis., 276393.","DOI":"10.4061\/2011\/276393"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"46","DOI":"10.2174\/1877944111202010046","article-title":"Aluminum induced immunoexcitotoxicity in neurodevelopmental and neurode-generative disorders","volume":"2","author":"Blaylock","year":"2012","journal-title":"Curr. Inorg. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1016\/j.jinorgbio.2009.08.005","article-title":"Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction","volume":"103","author":"Passeri","year":"2009","journal-title":"J. Inorg. Biochem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1177\/0961203311429316","article-title":"The spectrum of ASIA: \u2018Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants\u2019","volume":"21","author":"Hughes","year":"2012","journal-title":"Lupus"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/j.jinorgbio.2011.08.006","article-title":"Long-term follow-up of cognitive dysfunction in patients with aluminum hydroxide-induced macrophagic myofasciitis (MMF)","volume":"105","author":"Passeri","year":"2011","journal-title":"J. Inorg. Biochem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1289\/ehp.8563141","article-title":"Water content of aluminum, dialysis dementia, and osteomalacia","volume":"63","author":"Wills","year":"1985","journal-title":"Environ. Health Persp."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1046\/j.1471-4159.1999.0730712.x","article-title":"Prenatal exposure to aluminum reduces expression of neuronal nitric oxide synthase and of soluble guanylate cyclase and impairs glutamatergic neurotransmission in rat cerebellum","volume":"73","author":"Llansola","year":"1999","journal-title":"J. Neurochem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/j.jinorgbio.2011.07.001","article-title":"Aluminum toxicity and astrocyte dysfunction: A metabolic link to neurological disorders","volume":"105","author":"Lemire","year":"2011","journal-title":"Inorg. Biochem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1002\/jnr.21965","article-title":"Aluminum-induced defective mitochondrial metabolism perturbs cytoskeletal dynamics in human astrocytoma cells","volume":"87","author":"Lemire","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/j.1600-0773.1992.tb00471.x","article-title":"Aluminium-adjuvanted vaccines transiently increase aluminium levels in murine brain tissue","volume":"70","author":"Redhead","year":"1992","journal-title":"Pharmacol. Toxicol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.bbi.2011.08.007","article-title":"The role of immune dysfunction in the pathophysiology of autism","volume":"26","author":"Onore","year":"2012","journal-title":"Brain Behav. Immun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.cbpa.2006.09.020","article-title":"Interactions between macromolecules and ions: The Hofmeister series","volume":"10","author":"Zhang","year":"2006","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1001\/jama.293.13.1653","article-title":"The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: A novel mechanism of human disease","volume":"293","author":"Rother","year":"2005","journal-title":"JAMA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1111\/j.1365-3016.2008.00973.x","article-title":"Neonatal jaundice: A risk factor for infantile autism?","volume":"22","author":"Maimburg","year":"2008","journal-title":"Paediatr. Perinat. Ep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1542\/peds.2010-0052","article-title":"Neonatal jaundice, Autism, and other disorders of psychological development","volume":"126","author":"Maimburg","year":"2010","journal-title":"Pediatrics"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1182\/blood.V88.5.1857.1857","article-title":"Nitric oxide interactions with cobalamins: Biochemical and functional consequences","volume":"88","author":"Brouwer","year":"1996","journal-title":"Blood"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1756-8722-1-26","article-title":"Hemolysis and hyperhomocysteinemia caused by cobalamin deficiency: Three case reports and review of the literature","volume":"1","author":"Acharya","year":"2008","journal-title":"J. Hematol. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"11723","DOI":"10.1002\/chem.201102267","article-title":"Kinetic studies on the reaction between cob(I)alamin and peroxynitrite: Rapid oxidation of cob(I)alamin to cob(II)alamin by peroxynitrous acid","volume":"17","author":"Mukherjee","year":"2011","journal-title":"Chem. Eur. J."},{"key":"ref_111","unstructured":"Liu, J., Li, A., and Seneff, S. (, January October). Automatic drug side effect discovery from online patient-submitted reviews: Focus on statin drugs. Proceedings of the first international conference on advances in information mining and management, Barcelona, Spain."},{"key":"ref_112","first-page":"61","article-title":"Accurate methods for the statistics of surprise and coincidence","volume":"19","author":"Dunning","year":"1993","journal-title":"Comp. Ling."},{"key":"ref_113","unstructured":"PubMed Health, A.D.A.M. Medical Encyclopedia, Preeclampsia, Available on: http:\/\/www.ncbi.nlm.nih.gov\/pubmedhealth\/PMH0001900\/."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"S129","DOI":"10.1016\/S0039-6257(99)00010-7","article-title":"Nitric oxide: A potential mediator of retinal ganglion cell damage in glaucoma","volume":"43","author":"Neufeld","year":"1999","journal-title":"Surv. Ophthalmol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1002\/(SICI)1098-1136(200004)30:2<178::AID-GLIA7>3.0.CO;2-C","article-title":"Expression of nitric oxide synthase-2 (NOS-2) in reactive astrocytes of the human glaucomatous optic nerve head","volume":"30","author":"Liu","year":"2000","journal-title":"Glia"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1523\/JNEUROSCI.13-07-03034.1993","article-title":"Peptide growth factors protect against ischemia in culture by preventing nitric oxide toxicity","volume":"73","author":"Maiese","year":"1993","journal-title":"J. Neurosci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1542\/peds.3.3.308","article-title":"Cyanosis in infants with nitrates in drinking water as cause","volume":"3","author":"Donahoe","year":"1949","journal-title":"Pediatrics"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1542\/peds.59.2.280","article-title":"Sudden death in an infant from methemoglobinemia after administration of \u2018sweet spirits of nitre\u2019","volume":"59","author":"Chilcote","year":"1977","journal-title":"Pediatrics"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.vaccine.2010.09.020","article-title":"Guillain-Barr\u00e9 syndrome after Gardasil vaccination: data from Vaccine Adverse Event Reporting System 2006\u20132009","volume":"29","author":"Souayah","year":"2011","journal-title":"Vaccine"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1159\/000254898","article-title":"Erythema Multiforme following vaccination for human Papillomavirus","volume":"220","author":"Katoulis","year":"2010","journal-title":"Dermatology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/0002-9378(94)90463-4","article-title":"A new animal model for human preeclampsia: Ultra-low-dose endotoxin infusion in pregnant rats","volume":"1171","author":"Faas","year":"1994","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_122","unstructured":"Hoffman, R., Benz, E.J., and Shattil, S.S. (2008). Hematology: Basic Principles and Practice, Elsevier Churchill Livingstone. [5th ed.]. Chapter 39."}],"container-title":["Entropy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1099-4300\/14\/11\/2265\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:53:24Z","timestamp":1760219604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1099-4300\/14\/11\/2265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,8]]},"references-count":122,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2012,11]]}},"alternative-id":["e14112265"],"URL":"https:\/\/doi.org\/10.3390\/e14112265","relation":{},"ISSN":["1099-4300"],"issn-type":[{"value":"1099-4300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,8]]}}}