Re: Flagyl and an inborn error of metabolism: important implications!

October 5, 2007

?

Remember I forwarded you with out the URL about FLUORIDE dedgradating oxylbacter forminges? I know that DIFLUCAN has a FLUORINE molecule in it, does FLAGYL too? This I don't know and can't find on any google search?

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Fluoride Template

Fluoride has even been shown to affect the pituitary gland, .... contain fluoride: Prozac (fluoxetine), Rohypnol (flunitrazepam), Diflucan (fluconazole, ...www.bcd.com.au/FluorideDocs/PoisoningSYmpts.htm - 27k - Cached - Similar pages - Note this

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http://www.level1diet.com/research/id/1274424

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http://www.rense.com/general60/nationalflouridedatabase.htm

One must also look at the growing number of fluorinated pharmaceutical products that have been widely prescribed, including, but certainly not limited to: Lariam, Cipro (ciprofloxacin), Crestor, Flonase, Lipitor, Luvox, Diflucan, Lexapro, Paxil, Lescol, Prozac, Stelazine, Haldol, Levaquin (levofloxacin), Celexa, Celebrex, Prevacid, Zagam, Tequin, Halfan, Propulsid, Advair Diskus,

Flovent, Baycol, Avelox, Redux, Trovan, Casodex and so on. Some of the above named pharmaceuticals have already been removed from the market due to side effects. -----------------------------------------------------------------------------------------------------------------------------------------------------------

http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6SYP-4KSVFTV-2 & _user=10 & _coverDate=01%2F10%2F2007 & _rdoc=1 & _fmt= & _orig=search & _sort=d & view=c & _acct=C000050221 & _version=1 & _urlVersion=0 & _userid=10 & md5=23811a872a8b7d3f1620d7eeeb2219f2

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It is also interesting that ingesting fluoride all the time wipes out your B-6 Vitamin and Enzyme activity, which would make the oxalate formation more easy in the body right?

per ........ Twelve male Wistar rats were randomized to two groups and were fed either a standard diet or a vitamin-B6-deficient diet for 3 weeks. Then the animals received an intravenous infusion of 100 mg/ml (960.6 mumol/ml) of hydroxypyruvate slowly over 10 min. Urine samples were collected just before hydroxypyruvate infusion and at hourly intervals until 5 h afterward. Urinary oxalate, glycolate, and citrate levels were measured by capillary ... Read More »» Published in Urol Res. 2007 Jun 13;

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Could the epidemic of autism also be blamed on poisoning our children slowly with FLUORIDE/Drugs containing often used in autism population that contain Fluoride, degradating enzymes in the gut further, and flora that then produces all these nasty neurotoxic stews?

Flagyl and an inborn error of metabolism: important implications!

Listmates,The first article I've put below talks about using flagyl to reduce the propionic acid produced by the flora in children with an inborn error of metabolism. This defect involves losing the activity of an enzyme called propionyl CoA carboxylase, which degrades propionic acid. There is no suggestion in this article that any microbe is in an overgrowth situation, but only that the normal amounts of propionic acid that is routinely degraded by our human intestinal cells (which would have the enzyme defect in these children) was not detoxifying normal amounts of propionic acid coming from the flora.This study's data supplies strong evidence that propionic acid produced in the gut is NOT mainly degraded by other microbes, but is instead reliant on our own intestinal cells' performance. The enzyme that is defective is a biotin-dependent enzyme and for that reason it is subject to loss of function if oxalate gets into the active site. (See article on transcarboxylase inhibition by oxalate below.)Flagyl, the drug they used to reduce the proprionic acid made by the flora, and other antibiotics they tested also kills oxalobacter formigenes, which is the oxalate-dependent microbe that we need to have in our flora because it degrades the oxalate in the gut. Oxalate, of course, like propionic acid, is another significant toxin. When oxalobacter is missing in the gut, the oxalate that does not get degraded may impair the very same enzyme that degrades propionic acid in intestinal cells because it is a carboxylase.If you think about it, any delayed negative effect from flagyl that was mediated by excesses of oxalate inhibiting propionyl CoA carboxylase would not occur in these children whose enzyme was already totally knocked out. You cannot worsen enzyme activity in someone who already has a complete lack of activity. Even so, the oxalate that might not get degraded after taking flagyl in these children might still knock out the activity of other carboxylases, making flagyl perhaps a worrisome long-time therapy because of its effect on oxalobacter formigenes. The article investigating flagyl as a therapy for this inborn error advised intermittent courses, because there was some lingering effect after the flagyl was discontinued that made a constant exposure to the antimicrobial unnecessary. Doesn't that sound familiar?In the light of the new article on propionic acid in autism that came out this week, this interplay with flagyl could explain why some kids just keep cycling between benefits on antimicrobial therapy and a loss of improvements when the therapy is discontinued. In our DAN! community, a specific set of symptoms have been labelled "clostridial" because of how flagyl has lowered the quanitity of propionic family compounds on urinary organic acid tests. Just as in these children with an inborn enzyme defect, the problem with propionic acid may not represent overgrowth of any microbe (except when there is other evidence of such overgrowth), but instead could be a problem (as in these children with the inborn error) in the handling of a normal toxic metabolite.Similarly, the problem with oxalates in many children may be HANDLING issues caused by losing the one microbe that can degrade oxalate most successfully. Maybe the better approach, compared to using an antimicrobial that may kill our "friends", is to restore the enzyme activity that oxalate impaired by lowering oxalate in the diet and by using other probiotics that less successfully degrade oxalate until Oxthera's oxalobacter formigenes product is finally able to be purchased as a drug about a year from now when their clinical trials are over.This information also puts a different slant on the parental observation that going low oxalate has gotten some kids completely off the antimicrobial merry-go-round. Now, doesn't it make sense why this good news happened? These fortunate children would be expected to have been those whose troubles caused by propionic acid (and related compounds) stemmed from the excess oxalate in their gut affecting the performance of carboxylase enzymes that are functioning in their own intestinal cells, and perhaps affecting other carboxylases functioning in other organs.Please do read the abstracts below for clarification.1: Arch Dis Child. 2000 Feb;82(2):169-72.LinksEffect of oral antibiotics on intestinal production of propionic acid.Mellon AF, Deshpande SA, Mathers JC, Bartlett K.Sir Spence Institute of Child Health, Royal Infirmary, Queen Road, Newcastle upon Tyne NE1 4LP, UK.BACKGROUND: Propionic acid derived from colonic bacterial fermentation contributes substantially to overall propionate load in children with disorders of propionate metabolism, and its reduction is important for adequate metabolic control. AIMS: To evaluate the in vitro and in vivo effects of antibiotic treatment on propionate production by colonic bacteria, and plasma propionate concentrations in a child with propionic acidaemia. METHODS: In vitro fermentation techniques were used to study the effects of addition of antibiotics (metronidazole, clindamycin, erythromycin, and vancomycin) on net faecal production of short chain fatty acids including propionic acid. Courses of oral antibiotics of 7 days duration were used to assess the in vivo effects on faecal propionate production and metabolic control including plasma propionate concentrations. RESULTS: Metronidazole produced the largest and most consistent reduction (77-84%) in the production in vitro of propionate from faecal homogenates. Oral administration of metronidazole reduced faecal propionate production by 43% within 24 hours of treatment; a 7 day course virtually eliminated it for the next 3 weeks. These reductions were accompanied by substantially lowered plasma propionate concentrations during the same period. CONCLUSIONS: Intermittent courses of oral metronidazole might be as effective as continuous treatment in reducing gut propionate production in children with disorders of propionate metabolism.PMID: 10648377 [PubMed - indexed for MEDLINE]Eur J Pediatr. 1998 Jan;157(1):50-2.[] LinksAn unusual late-onset case of propionic acidaemia: biochemical investigations, neuroradiological findings and mutation analysis.Pérez-Cerdá C, Merinero B, Martí M, Cabrera JC, Peña L, García MJ, Gangoiti J, Sanz P, Rodríguez-Pombo P, Hoenicka J, E, Muro S, Ugarte M.Centro de Diagnóstico de Enfermedades Moleculares, Department of Molecular Biology, CBMSO, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.We report a 5-year-old boy with propionic acidaemia who developed a rapidly fatal necrosis of the basal ganglia after an episode of clinical deterioration. Neither metabolic acidosis nor hyperammonaemia were present. Organic acid analysis in both urine and CSF showed increased levels of methylcitric and 3-hydroxypropionic acids. Propionic acidaemia was confirmed by demonstrating a propionyl-CoA carboxylase deficiency (11% of control value) in skin fibroblasts. DNA analysis revealed that the patient was a compound heterozygote for two mutations in the PCCB gene. CONCLUSION: Propionic acidaemia can present as a sudden and fatal neurological disease and not only as an organic aciduria with severe biochemical dis-turbances and progressive neurological deterioration.PMID: 9461363 [PubMed - indexed for MEDLINE]>J Biol Chem. 1969 Nov 10;244(21):5820-7.Related Articles, Links>[]>Transcarboxylase. VII. Exchange reactions and kinetics of oxalate inhibition.>>Northrop DB, Wood HG.>>PMID: 5350938 [PubMed - indexed for MEDLINE]Appl Environ Microbiol. 2002 August; 68(8): 3841-3847.Oxalobacter formigenes and Its Potential Role in Human HealthSylvia H. Duncan,1 J. ,1 Poonam Kaul,2 Ross P. Holmes,3 Milton J. ,4 and Colin S. 1*http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=124017Oxalate degradation by the anaerobic bacterium Oxalobacter formigenes is important for human health, helping to prevent hyperoxaluria and disorders such as the development of kidney stones. Oxalate-degrading activity cannot be detected in the gut flora of some individuals, possibly because Oxalobacter is susceptible to commonly used antimicrobials. Here, clarithromycin, doxycycline, and some other antibiotics inhibited oxalate degradation by two human strains of O. formigenes. These strains varied in their response to gut environmental factors, including exposure to gastric acidity and bile salts. O. formigenes strains established oxalate breakdown in fermentors which were preinoculated with fecal bacteria from individuals lacking oxalate-degrading activity. Reducing the concentration of oxalate in the medium reduced the numbers of O. formigenes bacteria. Oxalate degradation was established and maintained at dilution rates comparable to colonic transit times in healthy individuals. A single oral ingestion of O. formigenes by adult volunteers was, for the first time, shown to result in (i) reduced urinary oxalate excretion following administration of an oxalate load, (ii) the recovery of oxalate-degrading activity in feces, and (iii) prolonged retention of colonization.3: J Endourol. 2005 Jan-Feb;19(1):102-6.Effect of antibiotics on Oxalobacter formigenes colonization of humangastrointestinal tract.Mittal RD, Kumar R, Bid HK, Mittal B.Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical Sciences,Lucknow, India. ramamittalBACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in thehuman gastrointestinal tract that degrades oxalate and reduces its availabilityfor absorption. This bacterium is assumed to be antibiotic sensitive, andrepeated antibiotic therapies could eradicate it. The aim of the present studywas to determine the differences in the colonization by O. formigenes ofindividuals who had been on antibiotics for at least 5 days at the time of samplecollection and individuals who had not taken antibiotics for at least 3 months.PATIENTS AND METHODS: Stool samples were collected from 80 individuals withoutstone disease (35 with and 45 without antibiotic consumption) and 100 patientswith stone disease (20 with and 80 without antibiotic consumption). Oxalobacterformigenes was detected by a polymerase chain reaction-based method, and thepresence/absence of O. formigenes was correlated with urinary oxalateconcentrations. RESULTS: Lower percentages of individuals without stone diseaseand with stone disease who were consuming antibiotics had O. formigenescolonization than individuals without antibiotic consumption. Urinary oxalateconcentrations were higher in the individuals without O. formigenes than incolonized individuals. CONCLUSION: Our observations confirm a direct associationbetween antibiotic consumption and absence of O. formigenes. Absence ofintestinal O. formigenes could represent a pathogenic factor in calcium oxalateurolithiasis when antibiotics are prescribed generously.Publication Types:Comparative StudyPMID: 15735393 [PubMed - indexed for MEDLINE]J Endourol. 2005 Jan-Feb;19(1):102-6.[] LinksEffect of antibiotics on Oxalobacter formigenes colonization of human gastrointestinal tract.Mittal RD, Kumar R, Bid HK, Mittal B.Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. ramamittalBACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in the human gastrointestinal tract that degrades oxalate and reduces its availability for absorption. This bacterium is assumed to be antibiotic sensitive, and repeated antibiotic therapies could eradicate it. The aim of the present study was to determine the differences in the colonization by O. formigenes of individuals who had been on antibiotics for at least 5 days at the time of sample collection and individuals who had not taken antibiotics for at least 3 months. PATIENTS AND METHODS: Stool samples were collected from 80 individuals without stone disease (35 with and 45 without antibiotic consumption) and 100 patients with stone disease (20 with and 80 without antibiotic consumption). Oxalobacter formigenes was detected by a polymerase chain reaction-based method, and the presence/absence of O. formigenes was correlated with urinary oxalate concentrations. RESULTS: Lower percentages of individuals without stone disease and with stone disease who were consuming antibiotics had O. formigenes colonization than individuals without antibiotic consumption. Urinary oxalate concentrations were higher in the individuals without O. formigenes than in colonized individuals. CONCLUSION: Our observations confirm a direct association between antibiotic consumption and absence of O. formigenes. Absence of intestinal O. formigenes could represent a pathogenic factor in calcium oxalate urolithiasis when antibiotics are prescribed generously.PMID: 15735393 [PubMed - indexed for MEDLINE]MacFabe 2007 Intraventricular propionic acid & possible role in autism.pdfBehav Brain Res. 2007 Jan 10;176(1):149-69. Epub 2006 Sep 1.[] LinksNeurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders.MacFabe DF, Cain DP, -Capote K, lin AE, Hoffman JE, Boon F, AR, Kavaliers M, Ossenkopp KP.The Kilee Patchell- Autism Research Group, Department of Psychology, Division of Developmental Disabilities, University of Western Ontario, Social Science Centre, London, Canada. dmacfabeuwo (DOT) caClinical observations suggest that certain gut and dietary factors may transiently worsen symptoms in autism spectrum disorders (ASD), epilepsy and some inheritable metabolic disorders. Propionic acid (PPA) is a short chain fatty acid and an important intermediate of cellular metabolism. PPA is also a by-product of a subpopulation of human gut enterobacteria and is a common food preservative. We examined the behavioural, electrophysiological, neuropathological, and biochemical effects of treatment with PPA and related compounds in adult rats. Intraventricular infusions of PPA produced reversible repetitive dystonic behaviours, hyperactivity, turning behaviour, retropulsion, caudate spiking, and the progressive development of limbic kindled seizures, suggesting that this compound has central effects. Biochemical analyses of brain homogenates from PPA treated rats showed an increase in oxidative stress markers (e.g., lipid peroxidation and protein carbonylation) and glutathione S-transferase activity coupled with a decrease in glutathione and glutathione peroxidase activity. Neurohistological examinations of hippocampus and adjacent white matter (external capsule) of PPA treated rats revealed increased reactive astrogliosis (GFAP immunoreactivity) and activated microglia (CD68 immunoreactivity) suggestive of a neuroinflammatory process. This was coupled with a lack of cytotoxicity (cell counts, cleaved caspase 3' immunoreactivity), and an increase in phosphorylated CREB immunoreactivity. We propose that some types of autism may be partial forms of genetically inherited or acquired disorders involving altered PPA metabolism. Thus, intraventricular administration of PPA in rats may provide a means to model some aspects of human ASD in rats.PMID: 16950524 [PubMed - indexed for MEDLINE]-- Internal Virus Database is out-of-date.Checked by AVG Free Edition. Version: 7.5.484 / Virus Database: 269.12.0/957 - Release Date: 8/16/2007 1:46 PM

October 5, 2007

,

My son just finished a round of Flagyl. I've read through your post a

couple of times but am still unsure of the implications. Is Flagyl a

bad thing to be giving these kids in your opinion? Since my son just

finished flagyl and is still on fluconazole is there some precautionary

measures I should take. Would you advise to not give flagyl again if

needed?

thanks

October 6, 2007

, that is very interesting, thanks for posting. It would help explain oxalate 'contribution' to autism even in absence of leaky gut and their entering bloodstream, wouldn't it??couple of questions:1. you mention this new oxalate-eating bacteria will by prescription-only. Why? Isn't that a bit unusual for a probiotic??2. for those that cannot do low oxalate diet, and/or do not have access to prescription medicine, what is your feeling or experience on using herbs to help degrade oxalate? there may be more of them out there, but I am interested in this one in particular:Phyllanthus niruri (Quebra Pedra, Chanca Piedra):Urol Res. 2003 Feb;30(6):374-9. Epub 2003 Jan 21. Effects of an aqueous extract from Phyllantus niruri on calcium oxalate crystallization in vitro. Barros ME, Schor N, Boim MA. Nephrology Division, Escola ista de Medicina, Universidade Federal de São o, São o, Brazil. Phyllanthus niruri is a plant used in Brazilian folk medicine for the treatment of urolithiasis. It was previously observed that P. niruri shows no toxicity, potentially increases calculus voiding by stone forming patients and inhibits the endocytosis of calcium oxalate (CaOx) crystals by MDCK cells. In addition, in a rat model of urolithiasis it reduced calculus growth. In the present study, we evaluated the effect of an aqueous extract of P. niruri on CaOx crystallization in vitro. CaOx precipitation was induced by the addition of 0.1 M sodium oxalate to unfiltered urine samples from Wistar rats (n=14) and normal humans (n=18) in the presence or absence of P. niruri extract (0.25 mg/ml of urine). The presence of CaOx crystals was evaluated immediately and 24 h later. In vitro crystallization of human urine produced typical mono- and dihydrated CaOx crystals, but only a few typical CaOx crystals were found in rat urine. The presence of P. niruri extract did not inhibit CaOx precipitation and even more crystals were obtained, although they were significantly smaller than those in the control urine. Crystal aggregation observed 24 h after crystallization was also inhibited by P. niruri extract. The results showed an inhibitory effect of P. niruri extract on CaOx crystal growth and aggregation in human urine, suggesting that it may interfere with the early stages of stone formation and may represent an alternative form of treatment and/or prevention of urolithiasis Publication Types: * In Vitro * Research Support, Non-U.S. Gov't PMID: 12599017 [PubMed - indexed for MEDLINE]2: BJU Int. 2002 Jun;89(9):829-34. The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation. Freitas AM, Schor N, Boim MA. Nephrology Division, Universidade Federal de São o, Escola ista de Medicina, São o, Brazil. OBJECTIVE: To evaluate the effect of an aqueous extract of Phyllanthus niruri (Pn), a plant used in folk medicine to treat lithiasis, on the urinary excretion of endogenous inhibitors of lithogenesis, citrate, magnesium and glycosaminoglycans (GAGs). MATERIALS AND METHODS: The effect of chronic (42 days) administration of Pn (1.25 mg/mL/day, orally) was evaluated in a rat model of urolithiasis induced by the introduction of a calcium oxalate (CaOx) seed into the bladder of adult male Wistar rats. The animals were divided into four groups: a sham control (16 rats); a control+Pn (six); CaOx+water instead of Pn (14); and CaOx+Pn (22). Plasma and urine were collected after 42 days of treatment for biochemical analysis and the determination of urinary excretion of citrate, magnesium and GAGs. The animals were then killed and the calculi analysed. RESULTS: The creatinine clearance or urinary and plasma concentrations of Na+, K+, Ca2+, oxalate, phosphate and uric acid were unaffected by Pn or the induction of lithiasis. Treatment with Pn strongly inhibited the growth of the matrix calculus and reduced the number of stone satellites compared with the group receiving water. The calculi were eliminated or dissolved in some treated animals (three of 22). The urinary excretion of citrate and magnesium was unaffected by Pn treatment. However, the mean (sd) urinary concentration of GAGs was significantly lower in rats treated with CaOx+Pn, at 5.64 (0.86) mg/g creatinine, than when treated with CaOx + water, at 11.78 (2.21) mg/g creatinine. In contrast, the content of GAGs in the calculi was higher in the CaOx + Pn rats, at 48.0 (10.4) g/g calculus, than in the CaOx + water group, at 16.6 (9.6) g/g calculus. CONCLUSION: These results show that Pn has an inhibitory effect on crystal growth, which is independent of changes in the urinary excretion of citrate and Mg, but might be related to the higher incorporation of GAGs into the calculi. Publication Types: * Research Support, Non-U.S. Gov't PMID: 12010223 [PubMed - indexed for MEDLINE]3: Nephron. 1999;81(4):393-7. Phyllanthus niruri inhibits calcium oxalate endocytosis by renal tubular cells: its role in urolithiasis. Campos AH, Schor N. Nephrology Division, Department of Medicine, Universidade Federal de São o, Brazil. We investigated the in vitro effect of an aqueous extract of Phyllanthus niruri L. on a model of CaOx crystal endocytosis by Madin-Darby canine kidney cells. The extract exhibited a potent and effective non-concentration-dependent inhibitory effect on the CaOx crystal internalization. This response was present even at very high (pathologic) CaOx concentrations and no P. niruri L.-induced toxic effect could be detected. Biochemical analysis of culture media containing P. niruri L. did not provide any clues for the elucidation of the cellular pathways affected by this natural product. Although further studies are necessary for a better understanding of the role of P. niruri L. in urolithiasis, our findings show that this natural product could be an attractive alternative for the treatment of urinary stones. PMID: 10095174 [PubMed - indexed for MEDLINE]Effect of Extract of Phyllanthus Niruri on Crystal Deposition in Experimental UrolithiasisBarros ME, Lima R, Mercuri LP, Matos JR, Schor N, Boim MADepartment of Medicine, Renal Division, Federal University of Sao o, Sao o, SP, BrazilUrol Res. 2006; 34: 351-7Full text:http://www.brazjurol.com.br/january_february_2007/survey/Urological_Survey_Sampaio_114_115.htmnatasa--- In mb12 valtrex , Owens wrote:>> Listmates,> > The first article I've put below talks about using flagyl to reduce the > propionic acid produced by the flora in children with an inborn error of > metabolism. This defect involves losing the activity of an enzyme called > propionyl CoA carboxylase, which degrades propionic acid. There is no > suggestion in this article that any microbe is in an overgrowth situation, > but only that the normal amounts of propionic acid that is routinely > degraded by our human intestinal cells (which would have the enzyme defect > in these children) was not detoxifying normal amounts of propionic acid > coming from the flora.> > This study's data supplies strong evidence that propionic acid produced in > the gut is NOT mainly degraded by other microbes, but is instead reliant on > our own intestinal cells' performance. The enzyme that is defective is a > biotin-dependent enzyme and for that reason it is subject to loss of > function if oxalate gets into the active site. (See article on > transcarboxylase inhibition by oxalate below.)> > Flagyl, the drug they used to reduce the proprionic acid made by the flora, > and other antibiotics they tested also kills oxalobacter formigenes, which > is the oxalate-dependent microbe that we need to have in our flora because > it degrades the oxalate in the gut. Oxalate, of course, like propionic > acid, is another significant toxin. When oxalobacter is missing in the > gut, the oxalate that does not get degraded may impair the very same enzyme > that degrades propionic acid in intestinal cells because it is a > carboxylase.> > If you think about it, any delayed negative effect from flagyl that was > mediated by excesses of oxalate inhibiting propionyl CoA carboxylase would > not occur in these children whose enzyme was already totally knocked > out. You cannot worsen enzyme activity in someone who already has a > complete lack of activity. Even so, the oxalate that might not get > degraded after taking flagyl in these children might still knock out the > activity of other carboxylases, making flagyl perhaps a worrisome long-time > therapy because of its effect on oxalobacter formigenes. The article > investigating flagyl as a therapy for this inborn error advised > intermittent courses, because there was some lingering effect after the > flagyl was discontinued that made a constant exposure to the antimicrobial > unnecessary. Doesn't that sound familiar?> > In the light of the new article on propionic acid in autism that came out > this week, this interplay with flagyl could explain why some kids just keep > cycling between benefits on antimicrobial therapy and a loss of > improvements when the therapy is discontinued. In our DAN! community, a > specific set of symptoms have been labelled "clostridial" because of how > flagyl has lowered the quanitity of propionic family compounds on urinary > organic acid tests. Just as in these children with an inborn enzyme > defect, the problem with propionic acid may not represent overgrowth of any > microbe (except when there is other evidence of such overgrowth), but > instead could be a problem (as in these children with the inborn error) in > the handling of a normal toxic metabolite.> > Similarly, the problem with oxalates in many children may be HANDLING > issues caused by losing the one microbe that can degrade oxalate most > successfully. Maybe the better approach, compared to using an > antimicrobial that may kill our "friends", is to restore the enzyme > activity that oxalate impaired by lowering oxalate in the diet and by using > other probiotics that less successfully degrade oxalate until Oxthera's > oxalobacter formigenes product is finally able to be purchased as a drug > about a year from now when their clinical trials are over.> > This information also puts a different slant on the parental observation > that going low oxalate has gotten some kids completely off the > antimicrobial merry-go-round. Now, doesn't it make sense why this good > news happened? These fortunate children would be expected to have been > those whose troubles caused by propionic acid (and related compounds) > stemmed from the excess oxalate in their gut affecting the performance of > carboxylase enzymes that are functioning in their own intestinal cells, and > perhaps affecting other carboxylases functioning in other organs.> > Please do read the abstracts below for clarification.> > > > > 1: Arch Dis Child. 2000 Feb;82(2):169-72.Links> > Effect of oral antibiotics on intestinal production of propionic acid.> > Mellon AF, Deshpande SA, Mathers JC, Bartlett K.> > Sir Spence Institute of Child Health, Royal Infirmary, Queen > Road, Newcastle upon Tyne NE1 4LP, UK.> > BACKGROUND: Propionic acid derived from colonic bacterial fermentation > contributes substantially to overall propionate load in children with > disorders of propionate metabolism, and its reduction is important for > adequate metabolic control. AIMS: To evaluate the in vitro and in vivo > effects of antibiotic treatment on propionate production by colonic > bacteria, and plasma propionate concentrations in a child with propionic > acidaemia. METHODS: In vitro fermentation techniques were used to study the > effects of addition of antibiotics (metronidazole, clindamycin, > erythromycin, and vancomycin) on net faecal production of short chain fatty > acids including propionic acid. Courses of oral antibiotics of 7 days > duration were used to assess the in vivo effects on faecal propionate > production and metabolic control including plasma propionate > concentrations. RESULTS: Metronidazole produced the largest and most > consistent reduction (77-84%) in the production in vitro of propionate from > faecal homogenates. Oral administration of metronidazole reduced faecal > propionate production by 43% within 24 hours of treatment; a 7 day course > virtually eliminated it for the next 3 weeks. These reductions were > accompanied by substantially lowered plasma propionate concentrations > during the same period. CONCLUSIONS: Intermittent courses of oral > metronidazole might be as effective as continuous treatment in reducing gut > propionate production in children with disorders of propionate metabolism.> > PMID: 10648377 [PubMed - indexed for MEDLINE]> > Eur J Pediatr. 1998 Jan;157(1):50-2.[] Links> > An unusual late-onset case of propionic acidaemia: biochemical > investigations, neuroradiological findings and mutation analysis.> > Pérez-Cerdá C, Merinero B, Martí M, Cabrera JC, Peña L, García MJ, Gangoiti > J, Sanz P, Rodríguez-Pombo P, Hoenicka J, E, Muro S, Ugarte M.> > Centro de Diagnóstico de Enfermedades Moleculares, Department of Molecular > Biology, CBMSO, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.> > We report a 5-year-old boy with propionic acidaemia who developed a rapidly > fatal necrosis of the basal ganglia after an episode of clinical > deterioration. Neither metabolic acidosis nor hyperammonaemia were present. > Organic acid analysis in both urine and CSF showed increased levels of > methylcitric and 3-hydroxypropionic acids. Propionic acidaemia was > confirmed by demonstrating a propionyl-CoA carboxylase deficiency (11% of > control value) in skin fibroblasts. DNA analysis revealed that the patient > was a compound heterozygote for two mutations in the PCCB gene. CONCLUSION: > Propionic acidaemia can present as a sudden and fatal neurological disease > and not only as an organic aciduria with severe biochemical dis-turbances > and progressive neurological deterioration.> > PMID: 9461363 [PubMed - indexed for MEDLINE]> > > >J Biol Chem. 1969 Nov 10;244(21):5820-7.Related Articles, Links> >[]> >Transcarboxylase. VII. Exchange reactions and kinetics of oxalate inhibition.> >> >Northrop DB, Wood HG.> >> >PMID: 5350938 [PubMed - indexed for MEDLINE]> > Appl Environ Microbiol. 2002 August; 68(8): 3841–3847.> Oxalobacter formigenes and Its Potential Role in Human Health> Sylvia H. Duncan,1 J. ,1 Poonam Kaul,2 Ross P. Holmes,3 > Milton J. ,4 and Colin S. 1*> > http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=124017> > Oxalate degradation by the anaerobic bacterium Oxalobacter formigenes is > important for human health, helping to prevent hyperoxaluria and disorders > such as the development of kidney stones. Oxalate-degrading activity cannot > be detected in the gut flora of some individuals, possibly because > Oxalobacter is susceptible to commonly used antimicrobials. Here, > clarithromycin, doxycycline, and some other antibiotics inhibited oxalate > degradation by two human strains of O. formigenes. These strains varied in > their response to gut environmental factors, including exposure to gastric > acidity and bile salts. O. formigenes strains established oxalate breakdown > in fermentors which were preinoculated with fecal bacteria from individuals > lacking oxalate-degrading activity. Reducing the concentration of oxalate > in the medium reduced the numbers of O. formigenes bacteria. Oxalate > degradation was established and maintained at dilution rates comparable to > colonic transit times in healthy individuals. A single oral ingestion of O. > formigenes by adult volunteers was, for the first time, shown to result in > (i) reduced urinary oxalate excretion following administration of an > oxalate load, (ii) the recovery of oxalate-degrading activity in feces, and > (iii) prolonged retention of colonization.> > > > 3: J Endourol. 2005 Jan-Feb;19(1):102-6.> > Effect of antibiotics on Oxalobacter formigenes colonization of human> gastrointestinal tract.> > Mittal RD, Kumar R, Bid HK, Mittal B.> > Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical > Sciences,> Lucknow, India. ramamittal@...> > BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in the> human gastrointestinal tract that degrades oxalate and reduces its availability> for absorption. This bacterium is assumed to be antibiotic sensitive, and> repeated antibiotic therapies could eradicate it. The aim of the present study> was to determine the differences in the colonization by O. formigenes of> individuals who had been on antibiotics for at least 5 days at the time of > sample> collection and individuals who had not taken antibiotics for at least 3 months.> PATIENTS AND METHODS: Stool samples were collected from 80 individuals without> stone disease (35 with and 45 without antibiotic consumption) and 100 patients> with stone disease (20 with and 80 without antibiotic consumption). Oxalobacter> formigenes was detected by a polymerase chain reaction-based method, and the> presence/absence of O. formigenes was correlated with urinary oxalate> concentrations. RESULTS: Lower percentages of individuals without stone disease> and with stone disease who were consuming antibiotics had O. formigenes> colonization than individuals without antibiotic consumption. Urinary oxalate> concentrations were higher in the individuals without O. formigenes than in> colonized individuals. CONCLUSION: Our observations confirm a direct > association> between antibiotic consumption and absence of O. formigenes. Absence of> intestinal O. formigenes could represent a pathogenic factor in calcium oxalate> urolithiasis when antibiotics are prescribed generously.> > Publication Types:> Comparative Study> > PMID: 15735393 [PubMed - indexed for MEDLINE]> > > J Endourol. 2005 Jan-Feb;19(1):102-6.[] Links> > Effect of antibiotics on Oxalobacter formigenes colonization of human > gastrointestinal tract.> > Mittal RD, Kumar R, Bid HK, Mittal B.> > Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical > Sciences, Lucknow, India. ramamittal@...> > BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in > the human gastrointestinal tract that degrades oxalate and reduces its > availability for absorption. This bacterium is assumed to be antibiotic > sensitive, and repeated antibiotic therapies could eradicate it. The aim of > the present study was to determine the differences in the colonization by > O. formigenes of individuals who had been on antibiotics for at least 5 > days at the time of sample collection and individuals who had not taken > antibiotics for at least 3 months. PATIENTS AND METHODS: Stool samples were > collected from 80 individuals without stone disease (35 with and 45 without > antibiotic consumption) and 100 patients with stone disease (20 with and 80 > without antibiotic consumption). Oxalobacter formigenes was detected by a > polymerase chain reaction-based method, and the presence/absence of O. > formigenes was correlated with urinary oxalate concentrations. RESULTS: > Lower percentages of individuals without stone disease and with stone > disease who were consuming antibiotics had O. formigenes colonization than > individuals without antibiotic consumption. Urinary oxalate concentrations > were higher in the individuals without O. formigenes than in colonized > individuals. CONCLUSION: Our observations confirm a direct association > between antibiotic consumption and absence of O. formigenes. Absence of > intestinal O. formigenes could represent a pathogenic factor in calcium > oxalate urolithiasis when antibiotics are prescribed generously.> > PMID: 15735393 [PubMed - indexed for MEDLINE]> > > MacFabe 2007 Intraventricular propionic acid & possible role in autism.pdf> > Behav Brain Res. 2007 Jan 10;176(1):149-69. Epub 2006 Sep 1.[] Links> > Neurobiological effects of intraventricular propionic acid in rats: > possible role of short chain fatty acids on the pathogenesis and > characteristics of autism spectrum disorders.> > MacFabe DF, Cain DP, -Capote K, lin AE, Hoffman JE, Boon F, > AR, Kavaliers M, Ossenkopp KP.> > The Kilee Patchell- Autism Research Group, Department of Psychology, > Division of Developmental Disabilities, University of Western Ontario, > Social Science Centre, London, Canada. dmacfabe@...> > Clinical observations suggest that certain gut and dietary factors may > transiently worsen symptoms in autism spectrum disorders (ASD), epilepsy > and some inheritable metabolic disorders. Propionic acid (PPA) is a short > chain fatty acid and an important intermediate of cellular metabolism. PPA > is also a by-product of a subpopulation of human gut enterobacteria and is > a common food preservative. We examined the behavioural, > electrophysiological, neuropathological, and biochemical effects of > treatment with PPA and related compounds in adult rats. Intraventricular > infusions of PPA produced reversible repetitive dystonic behaviours, > hyperactivity, turning behaviour, retropulsion, caudate spiking, and the > progressive development of limbic kindled seizures, suggesting that this > compound has central effects. Biochemical analyses of brain homogenates > from PPA treated rats showed an increase in oxidative stress markers (e.g., > lipid peroxidation and protein carbonylation) and glutathione S-transferase > activity coupled with a decrease in glutathione and glutathione peroxidase > activity. Neurohistological examinations of hippocampus and adjacent white > matter (external capsule) of PPA treated rats revealed increased reactive > astrogliosis (GFAP immunoreactivity) and activated microglia (CD68 > immunoreactivity) suggestive of a neuroinflammatory process. This was > coupled with a lack of cytotoxicity (cell counts, cleaved caspase 3' > immunoreactivity), and an increase in phosphorylated CREB immunoreactivity. > We propose that some types of autism may be partial forms of genetically > inherited or acquired disorders involving altered PPA metabolism. Thus, > intraventricular administration of PPA in rats may provide a means to model > some aspects of human ASD in rats.> > PMID: 16950524 [PubMed - indexed for MEDLINE]> > > -- > Internal Virus Database is out-of-date.> Checked by AVG Free Edition. > Version: 7.5.484 / Virus Database: 269.12.0/957 - Release Date: 8/16/2007 1:46 PM>

October 6, 2007

Hi and Listmates,

I was jazzed to see this article and your post. If you remember I posted about

a year ago

in the DAN! Listserve about finding that MB12 is made by using propioni and

cyanocobalamin. Propioni was used to methylate or synergize methylcobalamin

from

cyanocobalamin.

Propioni became very interesting to me since I know my son had raised

colostridia levels

and because I have had adult acne for some time (as you know propioni is often

found in

dermititis).

Is it possible that propioni has both good and bad effects?

Something that has interested me for years is how sublingual and oral MB12

hardly works

for people in our community but works for a greater number of folks outside our

community (purely speaking through anecdotal reports). How could the transport

in the

mouth be affected... And why do our kids who need MB12 have high levels of

cyanocobalamin (B12).

Yes, I understand about enzyme activity and active trasport in the gut, but that

doesn't

explain a lack of sublingual absorption, especially in the face of such a

critical need for

MB12 in many of these kids --really a need for these families because I haven't

found an

MB12 responding child who doesnt have at least one parent who benefits from it

as well.

Then there is this recent discovery that has happened a few more times in the

last couple

of weeks. I have seen several adults who have been struggling with fungus try

mB12 nasal

spray and have had one of those dramatic responses that I commonly see. Two

sisters felt

fabulous, changed their lives, their mentality towards stress and anxiety and

life. Really

big effects... they clearly needed MB12.

Then about a week later of using it they are both complaining of yeast-like

symptoms.

Mentally they felt great, but the infection is growing. They didn't want to

give up MB12

but felt it was causing the infection to grow.

We have also seen parent reports say the same thing in the group.

I have often thought about MB12 being killed off in people who need it. I have

said that in

the early days of this group. I wonder if there is an infection in these kids

that end up

killing propioni and the growth and death of propioni in a struggle to survive

creates much

excess propionic acid which in turn creates some of the symptoms of autism. Not

in

inborn error (which of course wouldn't grow from 1 in 10,000 to 1 in 150 within

24 years),

but an infection.

However it happens, my belief is that many autisms are infections. Possibly an

infection

that commonly kills off the production of MB12 (maybe we should look for

infections that

coincide with high levels of cyanocobalamin)... anyway, an infection that

literally feeds on

the source of MB12 and starves the body of this amazing vitamin that helps it

relax, detox,

think clearly, process sensory input clearly, replecate DNA, fight viral

infections, etc. It

would be smart for an infection to kill MB12 because it would leave the body

more

vonerable for further infection and toxicity and stop DNA replication. If the

war is microbe

against human, this would be a great strategic move.

Then of course in the mix is the oxalate connection and everything you say I

don't doubt

as well. ( I want you to see the asthma videos I have of kids asthma's going

away from

MB12. We need to collaborate ideas more because I am convinced that asthma is

an

infection and oxalate crystals lodged in the lungs... I see this relationship

between MB12

and oxalates)

I'm just mixing in my view of the MB12 side of things.

I strongly believe this is a multi-tier infection at work... possibly clostridia

and/or virus

and/or fungus and/or other with multi-tiered affects like the brain starving

(the cortex

and more) from a lack of MB12 and the biological warefare in the gut that kills

off MB12

also causing oxalates and related downstream damage.

Please try to view this from a macro level, because if you get stuck in the

micro you could

criticize the banter but on a macro level I think it's darn pretty and it's been

speaking to

me for some time now.

- Stan

>

> Listmates,

>

> The first article I've put below talks about using flagyl to reduce the

> propionic acid produced by the flora in children with an inborn error of

> metabolism. This defect involves losing the activity of an enzyme called

> propionyl CoA carboxylase, which degrades propionic acid. There is no

> suggestion in this article that any microbe is in an overgrowth situation,

> but only that the normal amounts of propionic acid that is routinely

> degraded by our human intestinal cells (which would have the enzyme defect

> in these children) was not detoxifying normal amounts of propionic acid

> coming from the flora.

>

> This study's data supplies strong evidence that propionic acid produced in

> the gut is NOT mainly degraded by other microbes, but is instead reliant on

> our own intestinal cells' performance. The enzyme that is defective is a

> biotin-dependent enzyme and for that reason it is subject to loss of

> function if oxalate gets into the active site. (See article on

> transcarboxylase inhibition by oxalate below.)

>

> Flagyl, the drug they used to reduce the proprionic acid made by the flora,

> and other antibiotics they tested also kills oxalobacter formigenes, which

> is the oxalate-dependent microbe that we need to have in our flora because

> it degrades the oxalate in the gut. Oxalate, of course, like propionic

> acid, is another significant toxin. When oxalobacter is missing in the

> gut, the oxalate that does not get degraded may impair the very same enzyme

> that degrades propionic acid in intestinal cells because it is a

> carboxylase.

>

> If you think about it, any delayed negative effect from flagyl that was

> mediated by excesses of oxalate inhibiting propionyl CoA carboxylase would

> not occur in these children whose enzyme was already totally knocked

> out. You cannot worsen enzyme activity in someone who already has a

> complete lack of activity. Even so, the oxalate that might not get

> degraded after taking flagyl in these children might still knock out the

> activity of other carboxylases, making flagyl perhaps a worrisome long-time

> therapy because of its effect on oxalobacter formigenes. The article

> investigating flagyl as a therapy for this inborn error advised

> intermittent courses, because there was some lingering effect after the

> flagyl was discontinued that made a constant exposure to the antimicrobial

> unnecessary. Doesn't that sound familiar?

>

> In the light of the new article on propionic acid in autism that came out

> this week, this interplay with flagyl could explain why some kids just keep

> cycling between benefits on antimicrobial therapy and a loss of

> improvements when the therapy is discontinued. In our DAN! community, a

> specific set of symptoms have been labelled " clostridial " because of how

> flagyl has lowered the quanitity of propionic family compounds on urinary

> organic acid tests. Just as in these children with an inborn enzyme

> defect, the problem with propionic acid may not represent overgrowth of any

> microbe (except when there is other evidence of such overgrowth), but

> instead could be a problem (as in these children with the inborn error) in

> the handling of a normal toxic metabolite.

>

> Similarly, the problem with oxalates in many children may be HANDLING

> issues caused by losing the one microbe that can degrade oxalate most

> successfully. Maybe the better approach, compared to using an

> antimicrobial that may kill our " friends " , is to restore the enzyme

> activity that oxalate impaired by lowering oxalate in the diet and by using

> other probiotics that less successfully degrade oxalate until Oxthera's

> oxalobacter formigenes product is finally able to be purchased as a drug

> about a year from now when their clinical trials are over.

>

> This information also puts a different slant on the parental observation

> that going low oxalate has gotten some kids completely off the

> antimicrobial merry-go-round. Now, doesn't it make sense why this good

> news happened? These fortunate children would be expected to have been

> those whose troubles caused by propionic acid (and related compounds)

> stemmed from the excess oxalate in their gut affecting the performance of

> carboxylase enzymes that are functioning in their own intestinal cells, and

> perhaps affecting other carboxylases functioning in other organs.

>

> Please do read the abstracts below for clarification.

>

> 1: Arch Dis Child. 2000 Feb;82(2):169-72.Links

>

> Effect of oral antibiotics on intestinal production of propionic acid.

>

> Mellon AF, Deshpande SA, Mathers JC, Bartlett K.

>

> Sir Spence Institute of Child Health, Royal Infirmary, Queen

> Road, Newcastle upon Tyne NE1 4LP, UK.

>

> BACKGROUND: Propionic acid derived from colonic bacterial fermentation

> contributes substantially to overall propionate load in children with

> disorders of propionate metabolism, and its reduction is important for

> adequate metabolic control. AIMS: To evaluate the in vitro and in vivo

> effects of antibiotic treatment on propionate production by colonic

> bacteria, and plasma propionate concentrations in a child with propionic

> acidaemia. METHODS: In vitro fermentation techniques were used to study the

> effects of addition of antibiotics (metronidazole, clindamycin,

> erythromycin, and vancomycin) on net faecal production of short chain fatty

> acids including propionic acid. Courses of oral antibiotics of 7 days

> duration were used to assess the in vivo effects on faecal propionate

> production and metabolic control including plasma propionate

> concentrations. RESULTS: Metronidazole produced the largest and most

> consistent reduction (77-84%) in the production in vitro of propionate from

> faecal homogenates. Oral administration of metronidazole reduced faecal

> propionate production by 43% within 24 hours of treatment; a 7 day course

> virtually eliminated it for the next 3 weeks. These reductions were

> accompanied by substantially lowered plasma propionate concentrations

> during the same period. CONCLUSIONS: Intermittent courses of oral

> metronidazole might be as effective as continuous treatment in reducing gut

> propionate production in children with disorders of propionate metabolism.

>

> PMID: 10648377 [PubMed - indexed for MEDLINE]

>

> Eur J Pediatr. 1998 Jan;157(1):50-2.[] Links

>

> An unusual late-onset case of propionic acidaemia: biochemical

> investigations, neuroradiological findings and mutation analysis.

>

> Pérez-Cerdá C, Merinero B, Martí M, Cabrera JC, Peña L, García MJ, Gangoiti

> J, Sanz P, Rodríguez-Pombo P, Hoenicka J, E, Muro S, Ugarte M.

>

> Centro de Diagnóstico de Enfermedades Moleculares, Department of Molecular

> Biology, CBMSO, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.

>

> We report a 5-year-old boy with propionic acidaemia who developed a rapidly

> fatal necrosis of the basal ganglia after an episode of clinical

> deterioration. Neither metabolic acidosis nor hyperammonaemia were present.

> Organic acid analysis in both urine and CSF showed increased levels of

> methylcitric and 3-hydroxypropionic acids. Propionic acidaemia was

> confirmed by demonstrating a propionyl-CoA carboxylase deficiency (11% of

> control value) in skin fibroblasts. DNA analysis revealed that the patient

> was a compound heterozygote for two mutations in the PCCB gene. CONCLUSION:

> Propionic acidaemia can present as a sudden and fatal neurological disease

> and not only as an organic aciduria with severe biochemical dis-turbances

> and progressive neurological deterioration.

>

> PMID: 9461363 [PubMed - indexed for MEDLINE]

>

> >J Biol Chem. 1969 Nov 10;244(21):5820-7.Related Articles, Links

> >[]

> >Transcarboxylase. VII. Exchange reactions and kinetics of oxalate inhibition.

> >

> >Northrop DB, Wood HG.

> >

> >PMID: 5350938 [PubMed - indexed for MEDLINE]

>

> Appl Environ Microbiol. 2002 August; 68(8): 3841–3847.

> Oxalobacter formigenes and Its Potential Role in Human Health

> Sylvia H. Duncan,1 J. ,1 Poonam Kaul,2 Ross P. Holmes,3

> Milton J. ,4 and Colin S. 1*

>

> http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=124017

>

> Oxalate degradation by the anaerobic bacterium Oxalobacter formigenes is

> important for human health, helping to prevent hyperoxaluria and disorders

> such as the development of kidney stones. Oxalate-degrading activity cannot

> be detected in the gut flora of some individuals, possibly because

> Oxalobacter is susceptible to commonly used antimicrobials. Here,

> clarithromycin, doxycycline, and some other antibiotics inhibited oxalate

> degradation by two human strains of O. formigenes. These strains varied in

> their response to gut environmental factors, including exposure to gastric

> acidity and bile salts. O. formigenes strains established oxalate breakdown

> in fermentors which were preinoculated with fecal bacteria from individuals

> lacking oxalate-degrading activity. Reducing the concentration of oxalate

> in the medium reduced the numbers of O. formigenes bacteria. Oxalate

> degradation was established and maintained at dilution rates comparable to

> colonic transit times in healthy individuals. A single oral ingestion of O.

> formigenes by adult volunteers was, for the first time, shown to result in

> (i) reduced urinary oxalate excretion following administration of an

> oxalate load, (ii) the recovery of oxalate-degrading activity in feces, and

> (iii) prolonged retention of colonization.

>

> 3: J Endourol. 2005 Jan-Feb;19(1):102-6.

>

> Effect of antibiotics on Oxalobacter formigenes colonization of human

> gastrointestinal tract.

>

> Mittal RD, Kumar R, Bid HK, Mittal B.

>

> Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical

> Sciences,

> Lucknow, India. ramamittal@...

>

> BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in the

> human gastrointestinal tract that degrades oxalate and reduces its

availability

> for absorption. This bacterium is assumed to be antibiotic sensitive, and

> repeated antibiotic therapies could eradicate it. The aim of the present study

> was to determine the differences in the colonization by O. formigenes of

> individuals who had been on antibiotics for at least 5 days at the time of

> sample

> collection and individuals who had not taken antibiotics for at least 3

months.

> PATIENTS AND METHODS: Stool samples were collected from 80 individuals without

> stone disease (35 with and 45 without antibiotic consumption) and 100 patients

> with stone disease (20 with and 80 without antibiotic consumption).

Oxalobacter

> formigenes was detected by a polymerase chain reaction-based method, and the

> presence/absence of O. formigenes was correlated with urinary oxalate

> concentrations. RESULTS: Lower percentages of individuals without stone

disease

> and with stone disease who were consuming antibiotics had O. formigenes

> colonization than individuals without antibiotic consumption. Urinary oxalate

> concentrations were higher in the individuals without O. formigenes than in

> colonized individuals. CONCLUSION: Our observations confirm a direct

> association

> between antibiotic consumption and absence of O. formigenes. Absence of

> intestinal O. formigenes could represent a pathogenic factor in calcium

oxalate

> urolithiasis when antibiotics are prescribed generously.

>

> Publication Types:

> Comparative Study

>

> PMID: 15735393 [PubMed - indexed for MEDLINE]

>

> J Endourol. 2005 Jan-Feb;19(1):102-6.[] Links

>

> Effect of antibiotics on Oxalobacter formigenes colonization of human

> gastrointestinal tract.

>

> Mittal RD, Kumar R, Bid HK, Mittal B.

>

> Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical

> Sciences, Lucknow, India. ramamittal@...

>

> BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in

> the human gastrointestinal tract that degrades oxalate and reduces its

> availability for absorption. This bacterium is assumed to be antibiotic

> sensitive, and repeated antibiotic therapies could eradicate it. The aim of

> the present study was to determine the differences in the colonization by

> O. formigenes of individuals who had been on antibiotics for at least 5

> days at the time of sample collection and individuals who had not taken

> antibiotics for at least 3 months. PATIENTS AND METHODS: Stool samples were

> collected from 80 individuals without stone disease (35 with and 45 without

> antibiotic consumption) and 100 patients with stone disease (20 with and 80

> without antibiotic consumption). Oxalobacter formigenes was detected by a

> polymerase chain reaction-based method, and the presence/absence of O.

> formigenes was correlated with urinary oxalate concentrations. RESULTS:

> Lower percentages of individuals without stone disease and with stone

> disease who were consuming antibiotics had O. formigenes colonization than

> individuals without antibiotic consumption. Urinary oxalate concentrations

> were higher in the individuals without O. formigenes than in colonized

> individuals. CONCLUSION: Our observations confirm a direct association

> between antibiotic consumption and absence of O. formigenes. Absence of

> intestinal O. formigenes could represent a pathogenic factor in calcium

> oxalate urolithiasis when antibiotics are prescribed generously.

>

> PMID: 15735393 [PubMed - indexed for MEDLINE]

>

> MacFabe 2007 Intraventricular propionic acid & possible role in autism.pdf

>

> Behav Brain Res. 2007 Jan 10;176(1):149-69. Epub 2006 Sep 1.[] Links

>

> Neurobiological effects of intraventricular propionic acid in rats:

> possible role of short chain fatty acids on the pathogenesis and

> characteristics of autism spectrum disorders.

>

> MacFabe DF, Cain DP, -Capote K, lin AE, Hoffman JE, Boon F,

> AR, Kavaliers M, Ossenkopp KP.

>

> The Kilee Patchell- Autism Research Group, Department of Psychology,

> Division of Developmental Disabilities, University of Western Ontario,

> Social Science Centre, London, Canada. dmacfabe@...

>

> Clinical observations suggest that certain gut and dietary factors may

> transiently worsen symptoms in autism spectrum disorders (ASD), epilepsy

> and some inheritable metabolic disorders. Propionic acid (PPA) is a short

> chain fatty acid and an important intermediate of cellular metabolism. PPA

> is also a by-product of a subpopulation of human gut enterobacteria and is

> a common food preservative. We examined the behavioural,

> electrophysiological, neuropathological, and biochemical effects of

> treatment with PPA and related compounds in adult rats. Intraventricular

> infusions of PPA produced reversible repetitive dystonic behaviours,

> hyperactivity, turning behaviour, retropulsion, caudate spiking, and the

> progressive development of limbic kindled seizures, suggesting that this

> compound has central effects. Biochemical analyses of brain homogenates

> from PPA treated rats showed an increase in oxidative stress markers (e.g.,

> lipid peroxidation and protein carbonylation) and glutathione S-transferase

> activity coupled with a decrease in glutathione and glutathione peroxidase

> activity. Neurohistological examinations of hippocampus and adjacent white

> matter (external capsule) of PPA treated rats revealed increased reactive

> astrogliosis (GFAP immunoreactivity) and activated microglia (CD68

> immunoreactivity) suggestive of a neuroinflammatory process. This was

> coupled with a lack of cytotoxicity (cell counts, cleaved caspase 3'

> immunoreactivity), and an increase in phosphorylated CREB immunoreactivity.

> We propose that some types of autism may be partial forms of genetically

> inherited or acquired disorders involving altered PPA metabolism. Thus,

> intraventricular administration of PPA in rats may provide a means to model

> some aspects of human ASD in rats.

>

> PMID: 16950524 [PubMed - indexed for MEDLINE]

>

> --

> Internal Virus Database is out-of-date.

> Checked by AVG Free Edition.

> Version: 7.5.484 / Virus Database: 269.12.0/957 - Release Date: 8/16/2007 1:46

PM

>

October 6, 2007

Helicobacter pylori--is it a novel causative agent in Vitamin B12 deficiency? Arch Intern Med. 2000; 160(9):1349-53 (ISSN: 0003-9926) Kaptan K; Beyan C; Ural AU; Cetin T; Avcu F; Gül?en M; Finci R; Yalçín ADepartment of Hematology, Gülhane Military Medical

Academy, Ankara, Turkey. kkaptan@... BACKGROUND: Evidence for vitamin B12 deficiency usually involves combinations of low serum vitamin B12 levels, clinical and metabolic abnormalities, and therapeutic response. Identification of the underlying cause is important in the diagnosis of vitamin B12 deficiency that is usually attributed to malabsorption. Helicobacter pylori is one of the most common causes of peptic ulcer disease worldwide and a major cause of chronic superficial gastritis leading to atrophy of gastric glands. It is suggested that there may be a casual relationship between H. pylori and food-cobalamin malabsorption. OBJECTIVES: To evaluate the H. pylori incidence in patients with vitamin B12 deficiency prospectively and to assess whether treatment for H pylori infection could correct this deficiency over time. PATIENTS AND METHODS: We performed a prospective cohort study involving 138 patients who

had anemia and vitamin B12 deficiency. An upper gastrointestinal endoscopy was performed to assess the severity of atrophic gastritis and biopsy specimens for Campylobacter-like organisms tests and histological examination for H pylori were obtained at the time of diagnosis. The diagnosis of H. pylori prompted a combination treatment. RESULTS: Helicobacter pylori was detected in 77 (56%) of 138 patients with vitamin B12 deficiency and eradication of H pylori infection successfully improved anemia and serum vitamin B12 levels in 31 (40 %) of 77 infected patients. CONCLUSIONS: Helicobacter pylori seems to be a causative agent in the development of adult vitamin B12 deficiency. Eradication of H. pylori infection alone may correct vitamin B12 levels and improve anemia in this subgroup of patients. ***I had to be treated for H pylori with antibiotics a few years after my last child was born, who is ASD. Had stomach bloating

that was noticed in the middle of the night. Looked like I was pregnant. My OBGYN did a blood test to detect it. Also, I am currently slightly anemic and hypothyroid, which I was also when pregnant. My OBGYN also noticed I had an enlarged thyroid (goiter), which he had an endocrinologist evaluate and observe.*** Dawn Stan Kurtz wrote: Hi and Listmates,I was jazzed to see this

article and your post. If you remember I posted about a year ago in the DAN! Listserve about finding that MB12 is made by using propioni and cyanocobalamin. Propioni was used to methylate or synergize methylcobalamin from cyanocobalamin. Propioni became very interesting to me since I know my son had raised colostridia levels and because I have had adult acne for some time (as you know propioni is often found in dermititis).Is it possible that propioni has both good and bad effects?Something that has interested me for years is how sublingual and oral MB12 hardly works for people in our community but works for a greater number of folks outside our community (purely speaking through anecdotal reports). How could the transport in the mouth be affected... And why do our kids who need MB12 have high levels of cyanocobalamin (B12). Yes, I understand about enzyme activity and active trasport in the gut, but that

doesn't explain a lack of sublingual absorption, especially in the face of such a critical need for MB12 in many of these kids --really a need for these families because I haven't found an MB12 responding child who doesnt have at least one parent who benefits from it as well.Then there is this recent discovery that has happened a few more times in the last couple of weeks. I have seen several adults who have been struggling with fungus try mB12 nasal spray and have had one of those dramatic responses that I commonly see. Two sisters felt fabulous, changed their lives, their mentality towards stress and anxiety and life. Really big effects... they clearly needed MB12.Then about a week later of using it they are both complaining of yeast-like symptoms. Mentally they felt great, but the infection is growing. They didn't want to give up MB12 but felt it was causing the infection to grow.We have also seen parent

reports say the same thing in the group.I have often thought about MB12 being killed off in people who need it. I have said that in the early days of this group. I wonder if there is an infection in these kids that end up killing propioni and the growth and death of propioni in a struggle to survive creates much excess propionic acid which in turn creates some of the symptoms of autism. Not in inborn error (which of course wouldn't grow from 1 in 10,000 to 1 in 150 within 24 years), but an infection.However it happens, my belief is that many autisms are infections. Possibly an infection that commonly kills off the production of MB12 (maybe we should look for infections that coincide with high levels of cyanocobalamin)... anyway, an infection that literally feeds on the source of MB12 and starves the body of this amazing vitamin that helps it relax, detox, think clearly, process sensory input clearly, replecate DNA,

fight viral infections, etc. It would be smart for an infection to kill MB12 because it would leave the body more vonerable for further infection and toxicity and stop DNA replication. If the war is microbe against human, this would be a great strategic move.Then of course in the mix is the oxalate connection and everything you say I don't doubt as well. ( I want you to see the asthma videos I have of kids asthma's going away from MB12. We need to collaborate ideas more because I am convinced that asthma is an infection and oxalate crystals lodged in the lungs... I see this relationship between MB12 and oxalates)I'm just mixing in my view of the MB12 side of things.I strongly believe this is a multi-tier infection at work... possibly clostridia and/or virus and/or fungus and/or other with multi-tiered affects like the brain starving (the cortex and more) from a lack of MB12 and the biological warefare in the gut

that kills off MB12 also causing oxalates and related downstream damage.Please try to view this from a macro level, because if you get stuck in the micro you could criticize the banter but on a macro level I think it's darn pretty and it's been speaking to me for some time now.- Stan>> Listmates,> > The first article I've put below talks about using flagyl to reduce the > propionic acid produced by the flora in children with an inborn error of > metabolism. This defect involves losing the activity of an enzyme called > propionyl CoA carboxylase, which degrades propionic acid. There is no > suggestion in this article that any microbe is in an overgrowth situation, > but only that the normal amounts of propionic acid that is routinely >

degraded by our human intestinal cells (which would have the enzyme defect > in these children) was not detoxifying normal amounts of propionic acid > coming from the flora.> > This study's data supplies strong evidence that propionic acid produced in > the gut is NOT mainly degraded by other microbes, but is instead reliant on > our own intestinal cells' performance. The enzyme that is defective is a > biotin-dependent enzyme and for that reason it is subject to loss of > function if oxalate gets into the active site. (See article on > transcarboxylase inhibition by oxalate below.)> > Flagyl, the drug they used to reduce the proprionic acid made by the flora, > and other antibiotics they tested also kills oxalobacter formigenes, which > is the oxalate-dependent microbe that we need to have in our flora because > it degrades the oxalate in the gut. Oxalate, of course, like

propionic > acid, is another significant toxin. When oxalobacter is missing in the > gut, the oxalate that does not get degraded may impair the very same enzyme > that degrades propionic acid in intestinal cells because it is a > carboxylase.> > If you think about it, any delayed negative effect from flagyl that was > mediated by excesses of oxalate inhibiting propionyl CoA carboxylase would > not occur in these children whose enzyme was already totally knocked > out. You cannot worsen enzyme activity in someone who already has a > complete lack of activity. Even so, the oxalate that might not get > degraded after taking flagyl in these children might still knock out the > activity of other carboxylases, making flagyl perhaps a worrisome long-time > therapy because of its effect on oxalobacter formigenes. The article > investigating flagyl as a therapy for this inborn error

advised > intermittent courses, because there was some lingering effect after the > flagyl was discontinued that made a constant exposure to the antimicrobial > unnecessary. Doesn't that sound familiar?> > In the light of the new article on propionic acid in autism that came out > this week, this interplay with flagyl could explain why some kids just keep > cycling between benefits on antimicrobial therapy and a loss of > improvements when the therapy is discontinued. In our DAN! community, a > specific set of symptoms have been labelled "clostridial" because of how > flagyl has lowered the quanitity of propionic family compounds on urinary > organic acid tests. Just as in these children with an inborn enzyme > defect, the problem with propionic acid may not represent overgrowth of any > microbe (except when there is other evidence of such overgrowth), but > instead could be a

problem (as in these children with the inborn error) in > the handling of a normal toxic metabolite.> > Similarly, the problem with oxalates in many children may be HANDLING > issues caused by losing the one microbe that can degrade oxalate most > successfully. Maybe the better approach, compared to using an > antimicrobial that may kill our "friends", is to restore the enzyme > activity that oxalate impaired by lowering oxalate in the diet and by using > other probiotics that less successfully degrade oxalate until Oxthera's > oxalobacter formigenes product is finally able to be purchased as a drug > about a year from now when their clinical trials are over.> > This information also puts a different slant on the parental observation > that going low oxalate has gotten some kids completely off the > antimicrobial merry-go-round. Now, doesn't it make sense why this good

> news happened? These fortunate children would be expected to have been > those whose troubles caused by propionic acid (and related compounds) > stemmed from the excess oxalate in their gut affecting the performance of > carboxylase enzymes that are functioning in their own intestinal cells, and > perhaps affecting other carboxylases functioning in other organs.> > Please do read the abstracts below for clarification.> > > > > 1: Arch Dis Child. 2000 Feb;82(2):169-72.Links> > Effect of oral antibiotics on intestinal production of propionic acid.> > Mellon AF, Deshpande SA, Mathers JC, Bartlett K.> > Sir Spence Institute of Child Health, Royal Infirmary, Queen > Road, Newcastle upon Tyne NE1 4LP, UK.> > BACKGROUND: Propionic acid derived from colonic bacterial fermentation > contributes

substantially to overall propionate load in children with > disorders of propionate metabolism, and its reduction is important for > adequate metabolic control. AIMS: To evaluate the in vitro and in vivo > effects of antibiotic treatment on propionate production by colonic > bacteria, and plasma propionate concentrations in a child with propionic > acidaemia. METHODS: In vitro fermentation techniques were used to study the > effects of addition of antibiotics (metronidazole, clindamycin, > erythromycin, and vancomycin) on net faecal production of short chain fatty > acids including propionic acid. Courses of oral antibiotics of 7 days > duration were used to assess the in vivo effects on faecal propionate > production and metabolic control including plasma propionate > concentrations. RESULTS: Metronidazole produced the largest and most > consistent reduction (77-84%) in the production in

vitro of propionate from > faecal homogenates. Oral administration of metronidazole reduced faecal > propionate production by 43% within 24 hours of treatment; a 7 day course > virtually eliminated it for the next 3 weeks. These reductions were > accompanied by substantially lowered plasma propionate concentrations > during the same period. CONCLUSIONS: Intermittent courses of oral > metronidazole might be as effective as continuous treatment in reducing gut > propionate production in children with disorders of propionate metabolism.> > PMID: 10648377 [PubMed - indexed for MEDLINE]> > Eur J Pediatr. 1998 Jan;157(1):50-2.[] Links> > An unusual late-onset case of propionic acidaemia: biochemical > investigations, neuroradiological findings and mutation analysis.> > Pérez-Cerdá C, Merinero B, Martí M, Cabrera JC, Peña L, García MJ, Gangoiti > J, Sanz P,

Rodríguez-Pombo P, Hoenicka J, E, Muro S, Ugarte M.> > Centro de Diagnóstico de Enfermedades Moleculares, Department of Molecular > Biology, CBMSO, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.> > We report a 5-year-old boy with propionic acidaemia who developed a rapidly > fatal necrosis of the basal ganglia after an episode of clinical > deterioration. Neither metabolic acidosis nor hyperammonaemia were present. > Organic acid analysis in both urine and CSF showed increased levels of > methylcitric and 3-hydroxypropionic acids. Propionic acidaemia was > confirmed by demonstrating a propionyl-CoA carboxylase deficiency (11% of > control value) in skin fibroblasts. DNA analysis revealed that the patient > was a compound heterozygote for two mutations in the PCCB gene. CONCLUSION: > Propionic acidaemia can present as a sudden and fatal neurological disease

> and not only as an organic aciduria with severe biochemical dis-turbances > and progressive neurological deterioration.> > PMID: 9461363 [PubMed - indexed for MEDLINE]> > > >J Biol Chem. 1969 Nov 10;244(21):5820-7.Related Articles, Links> >[]> >Transcarboxylase. VII. Exchange reactions and kinetics of oxalate inhibition.> >> >Northrop DB, Wood HG.> >> >PMID: 5350938 [PubMed - indexed for MEDLINE]> > Appl Environ Microbiol. 2002 August; 68(8): 3841–3847.> Oxalobacter formigenes and Its Potential Role in Human Health> Sylvia H. Duncan,1 J. ,1 Poonam Kaul,2 Ross P. Holmes,3 > Milton J. ,4 and Colin S. 1*> > http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=124017>

> Oxalate degradation by the anaerobic bacterium Oxalobacter formigenes is > important for human health, helping to prevent hyperoxaluria and disorders > such as the development of kidney stones. Oxalate-degrading activity cannot > be detected in the gut flora of some individuals, possibly because > Oxalobacter is susceptible to commonly used antimicrobials. Here, > clarithromycin, doxycycline, and some other antibiotics inhibited oxalate > degradation by two human strains of O. formigenes. These strains varied in > their response to gut environmental factors, including exposure to gastric > acidity and bile salts. O. formigenes strains established oxalate breakdown > in fermentors which were preinoculated with fecal bacteria from individuals > lacking oxalate-degrading activity. Reducing the concentration of oxalate > in the medium reduced the numbers of O. formigenes bacteria. Oxalate

> degradation was established and maintained at dilution rates comparable to > colonic transit times in healthy individuals. A single oral ingestion of O. > formigenes by adult volunteers was, for the first time, shown to result in > (i) reduced urinary oxalate excretion following administration of an > oxalate load, (ii) the recovery of oxalate-degrading activity in feces, and > (iii) prolonged retention of colonization.> > > > 3: J Endourol. 2005 Jan-Feb;19(1):102-6.> > Effect of antibiotics on Oxalobacter formigenes colonization of human> gastrointestinal tract.> > Mittal RD, Kumar R, Bid HK, Mittal B.> > Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical > Sciences,> Lucknow, India. ramamittal@...> > BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in the> human

gastrointestinal tract that degrades oxalate and reduces its availability> for absorption. This bacterium is assumed to be antibiotic sensitive, and> repeated antibiotic therapies could eradicate it. The aim of the present study> was to determine the differences in the colonization by O. formigenes of> individuals who had been on antibiotics for at least 5 days at the time of > sample> collection and individuals who had not taken antibiotics for at least 3 months.> PATIENTS AND METHODS: Stool samples were collected from 80 individuals without> stone disease (35 with and 45 without antibiotic consumption) and 100 patients> with stone disease (20 with and 80 without antibiotic consumption). Oxalobacter> formigenes was detected by a polymerase chain reaction-based method, and the> presence/absence of O. formigenes was correlated with urinary oxalate> concentrations. RESULTS: Lower

percentages of individuals without stone disease> and with stone disease who were consuming antibiotics had O. formigenes> colonization than individuals without antibiotic consumption. Urinary oxalate> concentrations were higher in the individuals without O. formigenes than in> colonized individuals. CONCLUSION: Our observations confirm a direct > association> between antibiotic consumption and absence of O. formigenes. Absence of> intestinal O. formigenes could represent a pathogenic factor in calcium oxalate> urolithiasis when antibiotics are prescribed generously.> > Publication Types:> Comparative Study> > PMID: 15735393 [PubMed - indexed for MEDLINE]> > > J Endourol. 2005 Jan-Feb;19(1):102-6.[] Links> > Effect of antibiotics on Oxalobacter formigenes colonization of human > gastrointestinal tract.> > Mittal RD, Kumar

R, Bid HK, Mittal B.> > Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical > Sciences, Lucknow, India. ramamittal@...> > BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in > the human gastrointestinal tract that degrades oxalate and reduces its > availability for absorption. This bacterium is assumed to be antibiotic > sensitive, and repeated antibiotic therapies could eradicate it. The aim of > the present study was to determine the differences in the colonization by > O. formigenes of individuals who had been on antibiotics for at least 5 > days at the time of sample collection and individuals who had not taken > antibiotics for at least 3 months. PATIENTS AND METHODS: Stool samples were > collected from 80 individuals without stone disease (35 with and 45 without > antibiotic consumption) and 100 patients with stone disease

(20 with and 80 > without antibiotic consumption). Oxalobacter formigenes was detected by a > polymerase chain reaction-based method, and the presence/absence of O. > formigenes was correlated with urinary oxalate concentrations. RESULTS: > Lower percentages of individuals without stone disease and with stone > disease who were consuming antibiotics had O. formigenes colonization than > individuals without antibiotic consumption. Urinary oxalate concentrations > were higher in the individuals without O. formigenes than in colonized > individuals. CONCLUSION: Our observations confirm a direct association > between antibiotic consumption and absence of O. formigenes. Absence of > intestinal O. formigenes could represent a pathogenic factor in calcium > oxalate urolithiasis when antibiotics are prescribed generously.> > PMID: 15735393 [PubMed - indexed for MEDLINE]> >

> MacFabe 2007 Intraventricular propionic acid & possible role in autism.pdf> > Behav Brain Res. 2007 Jan 10;176(1):149-69. Epub 2006 Sep 1.[] Links> > Neurobiological effects of intraventricular propionic acid in rats: > possible role of short chain fatty acids on the pathogenesis and > characteristics of autism spectrum disorders.> > MacFabe DF, Cain DP, -Capote K, lin AE, Hoffman JE, Boon F, > AR, Kavaliers M, Ossenkopp KP.> > The Kilee Patchell- Autism Research Group, Department of Psychology, > Division of Developmental Disabilities, University of Western Ontario, > Social Science Centre, London, Canada. dmacfabe@...> > Clinical observations suggest that certain gut and dietary factors may > transiently worsen symptoms in autism spectrum disorders (ASD), epilepsy > and some inheritable metabolic disorders.

Propionic acid (PPA) is a short > chain fatty acid and an important intermediate of cellular metabolism. PPA > is also a by-product of a subpopulation of human gut enterobacteria and is > a common food preservative. We examined the behavioural, > electrophysiological, neuropathological, and biochemical effects of > treatment with PPA and related compounds in adult rats. Intraventricular > infusions of PPA produced reversible repetitive dystonic behaviours, > hyperactivity, turning behaviour, retropulsion, caudate spiking, and the > progressive development of limbic kindled seizures, suggesting that this > compound has central effects. Biochemical analyses of brain homogenates > from PPA treated rats showed an increase in oxidative stress markers (e.g., > lipid peroxidation and protein carbonylation) and glutathione S-transferase > activity coupled with a decrease in glutathione and

glutathione peroxidase > activity. Neurohistological examinations of hippocampus and adjacent white > matter (external capsule) of PPA treated rats revealed increased reactive > astrogliosis (GFAP immunoreactivity) and activated microglia (CD68 > immunoreactivity) suggestive of a neuroinflammatory process. This was > coupled with a lack of cytotoxicity (cell counts, cleaved caspase 3' > immunoreactivity), and an increase in phosphorylated CREB immunoreactivity. > We propose that some types of autism may be partial forms of genetically > inherited or acquired disorders involving altered PPA metabolism. Thus, > intraventricular administration of PPA in rats may provide a means to model > some aspects of human ASD in rats.> > PMID: 16950524 [PubMed - indexed for MEDLINE]> > > -- > Internal Virus Database is out-of-date.> Checked by AVG Free Edition.

> Version: 7.5.484 / Virus Database: 269.12.0/957 - Release Date: 8/16/2007 1:46 PM> ~ Bloom Where You're Planted ~

October 6, 2007

Dawn,

So many of the things you listed sound like oxalate-related problems that

happen when you have a leaky gut. Oxalate really targets the thyroid, and

makes people hypothyroid, but it also is associated with a lot of other

thyroid damage. Also, in a survey we did early on LOD, only about a fourth

who responded did not see a positive change in gut distension within the

first month. Also, oxalate can make someone anemic because the oxalate ion

can enter the active site of transferrin and substitute for the carboxylate

ion that usually binds iron. The problem in that is that the bond is so

strong that later, when transferrin is supposed to release its iron, it

cannot! This can lead to anemia, but you have to watch what test you do to

measure the iron deficiency because the iron is still there...it is just

trapped, so it cannot perform its usual functions.

Of course, if the antibiotic killed off the oxalate-degrading flora, then

that could be what got things started.

Why don't you join the Trying_Low_Oxalates listserve and

take a look at the info on these topics and see if you can find some other

adults with parallels. Ours is not just a list for autism...in fact, I

don't even mention autism in the description of the list. Even so, most

listmates do have children with autism, but many of them have had their own

issues resolve when they also went LOD.

I'll put a few article below to give you the gist for what I said above.

1: Ann Diagn Pathol. 2002 Feb;6(1):10-9.

Pathology of the autonomously functioning (hot) thyroid nodule.

Harach HR, Sánchez SS, ED.

Services of Pathology and Surgery, " Dr A. Oñativia " Endocrinology and

Metabolism

Hospital, Salta, Argentina.

We describe the pathologic findings of 73 clinically and scintigraphically

confirmed hot nodules. In general, hot nodules from an unselected group

primarily

treated by surgery were smaller and the sex ratio was closer to equality

compared

with the ample female predominance in the referral, pre-, and post-prophylaxis

groups. Malignancy was observed in six cases (8.2%) (5 follicular, 1

papillary).

Of the 67 benign tumors, 48 (71.6%) were adenomas which showed the

cytoarchitectural features of hot nodules described previously, and 19 (28.3%)

were less well-differentiated adenomas that included a few oxyphil tumors.

Intracolloid oxalate crystals from background thyroid tissue were present in 59

assessable cases (83%) overall, the majority showed more than occasional

crystals

that had a tendency to increase in number with decreasing morphologic

activity of

the thyroid epithelium. Thyroglobulin protein and mRNA stainings tended to be

more pronounced in cell cytoplasm of the tumors than in background thyroid.

This

study shows that hot nodules may show a wide morphologic spectrum of follicular

neoplasms and can be occasionally malignant. It is inferred from the

morphologic

and other findings that it is likely that some, if not all, of the primary

follicular cancers associated with hyperfunction arise by clonal

progression from

benign hot nodules. This progression is rare, probably because most hot nodules

present with the symptoms of hyperfunction and receive early treatment.

Copyright

2002 by W.B. Saunders Company

Publication Types:

Comparative Study

Research Support, Non-U.S. Gov't

PMID: 11842375 [PubMed - indexed for MEDLINE]

2: Am J Surg Pathol. 1993 Jul;17(7):698-705.

Birefringent (calcium oxalate) crystals in thyroid diseases. A

clinicopathological study with possible implications for differential

diagnosis.

Katoh R, Kawaoi A, Muramatsu A, Hemmi A, Suzuki K.

Department of Pathology, Yamanashi Medical University, Tamaho-cho, Japan.

To elucidate the nature and significance of calcium oxalate crystals in the

pathologic thyroid, we used polarized light microscopy to review 357 thyroid

lesions. Under polarized light, calcium oxalate crystals had brilliant

birefringence, and they were invariably identified within the colloid of

follicles. The highest prevalence of crystals (87.9%) was in nodular goiters;

they were also found in 60.0% of follicular adenomas and 33.3% of follicular

carcinomas. The prevalence of crystals in papillary carcinomas was very low

(5.4%). Therefore, the overall prevalence was 69.4% in benign nodules and

7.6% in

malignant nodules. A heavy deposit of crystals was seen only in benign nodules

except for one case of follicular carcinoma. Graves' disease, focal

thyroiditis,

and subacute thyroiditis showed low prevalence: 25.0, 46.9, and 40.0%,

respectively. In cases of toxic nodules, the crystals were sparsely identified

within nodules, but abundantly observed in surrounding inactive tissues.

Immunohistochemistry for thyroid hormones confirmed that the crystals tended to

appear in inactive follicles. On tissue x-ray film, the crystals appeared as

microcalcifications. As a result of these findings, we suggest that

examinations

of crystals are likely to be useful in the differential diagnosis of thyroid

diseases and in possible estimations of the functional state of lesions.

PMID: 8317610 [PubMed - indexed for MEDLINE]

3: Virchows Arch A Pathol Anat Histopathol. 1993;422(4):301-6.

Nature and significance of calcium oxalate crystals in normal human thyroid

gland. A clinicopathological and immunohistochemical study.

Katoh R, Suzuki K, Hemmi A, Kawaoi A.

Department of Pathology, Yamanashi Medical University, Japan.

To elucidate the significance and nature of calcium oxalate crystals in the

thyroid, we studied these crystals clinicopathologically and

immunohistochemically in 182 normal thyroids from patients autopsied within 5 h

of death. Under polarized light, calcium oxalate crystals showed brilliant

birefringence and were invariably found within the colloid. The crystals were

found in 73.1% of all cases but were more prevalent and denser in older

individuals, with the highest prevalence (85.2%) being observed in those

over 70

years of age. No crystals were seen in those under 10 years of age. Although

underlying diseases seemed to have little influence, post-mortem delay

apparently

affected the prevalence and density of occurrence since the crystals tended to

disappear with hours after death. An immunohistochemical study using

anti-thyroid

hormone antibodies revealed that the crystals were within negatively or weakly

stained colloid and were not common in strongly stained colloid. These findings

support the hypothesis that the occurrence of calcium oxalate crystals in

normal

human thyroid is associated with a low functional state of the thyroid

follicles.

PMID: 8506623 [PubMed - indexed for MEDLINE]

4: Scanning Microsc. 1988 Mar;2(1):241-6.

Presence of calcium oxalate crystals in the mammalian thyroid gland.

Hackett RL, Khan SR.

Department of Pathology, College of Medicine, University of Florida,

Gainesville.

Birefringent crystals of calcium oxalate have been previously identified in the

colloid of human thyroid glands. We found such crystals in 19/20 adult thyroids

at autopsy, in 4/20 infants at autopsy, and, using frozen sections, in 19/20

thyroids partially or totally removed at surgery. These crystals were

soluble in

hydrochloric acid, insoluble in acetic acid, and contained only calcium by

energy

dispersive X-ray microanalysis, confirming their calcium oxalate character.

Similar crystals were found in equine and ovine thyroids.

Publication Types:

Research Support, U.S. Gov't, P.H.S.

PMID: 3368759 [PubMed - indexed for MEDLINE]

5: Am J Clin Pathol. 1987 Apr;87(4):443-54.

Calcium oxalate crystals in the thyroid. Their identification, prevalence,

origin, and possible significance.

Reid JD, Choi CH, Oldroyd NO.

Calcium oxalate crystals are not encountered in normal animal tissues,

except for

the human thyroid, where they were found in 79 of 100 routine consecutive

autopsies. They appear during childhood, and numbers of crystals increase with

age. In diffuse hyperplasia, prevalence was higher, but crystals were fewer

than

expected. In adenomas and carcinomas, crystals were decreased except for three

cases with a striking focal increase. None was found in 22 adult primate

thyroids. After Clorox digestion of human thyroids, calcium oxalate

dihydrate was

identified by x-ray diffraction and infrared spectroscopy. Origin, tissue and

species localization are discussed in relation to ascorbate metabolism,

thyroperoxidase, and calcitonin. Possible metabolic roles are suggested.

Calcium

oxalate crystals injected in animals and humans initiate a foreign body

reaction

with giant cells. In Hashimoto's thyroiditis, crystals disappear but

occasionally

remain with giant cell reaction. In subacute thyroiditis, granulomas are

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 2435146 [PubMed - indexed for MEDLINE]

6: Verh Dtsch Ges Pathol. 1975;59:410-4.

[The occurrence of crystalline calcium oxalate in thyroid colloid in different

functional states and ages. A light and electron microscopic study (author's

transl)]

[Article in German]

Schaefer HE, Rentzschke RD.

Publication Types:

English Abstract

PMID: 1217053 [PubMed - indexed for MEDLINE]

1: J Control Release. 2007 Feb 26;117(3):403-12. Epub 2006 Dec 8.

Inhibition of transferrin iron release increases in vitro drug carrier

efficacy.

Lao BJ, Tsai WL, Mashayekhi F, Pham EA, Mason AB, Kamei DT.

Department of Bioengineering, University of California, Los Angeles, CA 90095,

USA.

Transferrin (Tf) conjugates of CRM107 are currently being tested in clinical

trials for treatment of malignant gliomas. However, the rapid cellular

recycling

of Tf limits its efficiency as a drug carrier. We have developed a mathematical

model of the Tf/TfR trafficking cycle and have identified the Tf iron release

rate as a previously unreported factor governing the degree of Tf cellular

association. The release of iron from Tf is inhibited by replacing the

synergistic carbonate anion with oxalate. Trafficking patterns for oxalate

Tf and

native Tf are compared by measuring their cellular association with HeLa cells.

The amount of Tf associated with the cells is an average of 51% greater for

oxalate Tf than for native Tf over a two hour period at Tf concentrations

of 0.1

nM and 1 nM. Importantly, diphtheria toxin (DT) conjugates of oxalate Tf

are more

cytotoxic against HeLa cells than conjugates of native Tf. Conjugate IC(50)

values were determined to be 0.06 nM for the oxalate Tf conjugate vs. 0.22

nM for

the native Tf conjugate. Thus, we show that inhibition of Tf iron release

improves the efficacy of Tf as a drug carrier through increased association

with

cells expressing TfR.

Publication Types:

Research Support, N.I.H., Extramural

Research Support, Non-U.S. Gov't

PMID: 17239470 [PubMed - indexed for MEDLINE]

2: J Mol Biol. 2004 May 21;339(1):217-26.

The oxalate effect on release of iron from human serum transferrin explained.

Halbrooks PJ, Mason AB, TE, Briggs SK, Everse SJ.

Department of Biochemistry, College of Medicine, University of Vermont, 89

Beaumont Avenue, Burlington, VT 05405, USA.

A unique feature of the mechanism of iron binding to the transferrin (TF)

family

is the synergistic relationship between metal binding and anion binding. Little

or no iron will bind to the protein without concomitant binding of an anion,

physiologically identified as carbonate. Substitution of oxalate for carbonate

produces no significant changes in polypeptide folding or domain orientation in

the N-lobe of human serum TF (hTF) as revealed by our 1.2A structure. The

oxalate

is able to bind to the iron in a symmetric bidentate fashion, which, combined

with the low pK(a) of the oxalate anion, makes iron displacement more difficult

as documented by both iron release kinetic and equilibrium data.

Characterization

of an N-lobe in which the arginine at position 124 is mutated to alanine

reveals

that the stabilizing effect of oxalate is even greater in this mutant and

nearly

cancels the destabilizing effect of the mutation. Importantly, incorporation of

oxalate as the synergistic anion appears to completely inhibit removal of iron

from recombinant full-length hTF by HeLa S(3) cells, strongly indicating that

oxalate also replaces carbonate in the C-lobe to form a stable complex. Kinetic

studies confirm this claim. The combination of structural and functional data

provides a coherent delineation of the effect of oxalate binding on hTF and

rationalizes the results of many previous studies. In the context of iron

uptake

by cells, substitution of carbonate by oxalate effectively locks the iron into

each lobe of hTF, thereby interfering with normal iron metabolism.

Publication Types:

Comparative Study

Research Support, U.S. Gov't, Non-P.H.S.

Research Support, U.S. Gov't, P.H.S.

PMID: 15123433 [PubMed - indexed for MEDLINE]

At 12:03 PM 10/6/2007, you wrote:

>

>Helicobacter pylori--is it a novel causative agent in Vitamin B12 deficiency?

>

><http://www.medscape.com/medline/publicationbrowser/123?pmid=10809040>Arch

>Intern Med. 2000; 160(9):1349-53 (ISSN: 0003-9926)

>

>Kaptan K; Beyan C; Ural AU; Cetin T; Avcu F; Gül?en M; Finci R; Yalçín A

>Department of Hematology, Gülhane Military Medical Academy, Ankara,

>Turkey. kkaptan@...

>BACKGROUND: Evidence for vitamin B12 deficiency usually involves

>combinations of low serum vitamin B12 levels, clinical and metabolic

>abnormalities, and therapeutic response. Identification of the underlying

>cause is important in the diagnosis of vitamin B12 deficiency that is

>usually attributed to malabsorption. Helicobacter pylori is one of the

>most common causes of peptic ulcer disease worldwide and a major cause of

>chronic superficial gastritis leading to atrophy of gastric glands. It is

>suggested that there may be a casual relationship between H. pylori and

>food-cobalamin malabsorption. OBJECTIVES: To evaluate the H. pylori

>incidence in patients with vitamin B12 deficiency prospectively and to

>assess whether treatment for H pylori infection could correct this

>deficiency over time. PATIENTS AND METHODS: We performed a prospective

>cohort study involving 138 patients who had anemia and vitamin B12

>deficiency. An upper gastrointestinal endoscopy was performed to assess

>the severity of atrophic gastritis and biopsy specimens for

>Campylobacter-like organisms tests and histological examination for H

>pylori were obtained at the time of diagnosis. The diagnosis of H. pylori

>prompted a combination treatment. RESULTS: Helicobacter pylori was

>detected in 77 (56%) of 138 patients with vitamin B12 deficiency and

>eradication of H pylori infection successfully improved anemia and serum

>vitamin B12 levels in 31 (40 %) of 77 infected patients. CONCLUSIONS:

>Helicobacter pylori seems to be a causative agent in the development of

>adult vitamin B12 deficiency. Eradication of H. pylori infection alone may

>correct vitamin B12 levels and improve anemia in this subgroup of patients.

>

>***I had to be treated for H pylori with antibiotics a few years after my

>last child was born, who is ASD. Had stomach bloating that was noticed

>in the middle of the night. Looked like I was pregnant. My OBGYN did a

>blood test to detect it. Also, I am currently slightly anemic and

>hypothyroid, which I was also when pregnant. My OBGYN also noticed I had

>an enlarged thyroid (goiter), which he had an endocrinologist evaluate and

>observe.*** Dawn

>

>Stan Kurtz wrote:

>Hi and Listmates,

>

>I was jazzed to see this article and your post. If you remember I posted

>about a year ago

>in the DAN! Listserve about finding that MB12 is made by using propioni and

>cyanocobalamin. Propioni was used to methylate or synergize

>methylcobalamin from

>cyanocobalamin.

>

>Propioni became very interesting to me since I know my son had raised

>colostridia levels

>and because I have had adult acne for some time (as you know propioni is

>often found in

>dermititis).

>

>Is it possible that propioni has both good and bad effects?

>

>Something that has interested me for years is how sublingual and oral MB12

>hardly works

>for people in our community but works for a greater number of folks

>outside our

>community (purely speaking through anecdotal reports). How could the

>transport in the

>mouth be affected... And why do our kids who need MB12 have high levels of

>cyanocobalamin (B12).

>

>Yes, I understand about enzyme activity and active trasport in the gut,

>but that doesn't

>explain a lack of sublingual absorption, especially in the face of such a

>critical need for

>MB12 in many of these kids --really a need for these families because I

>haven't found an

>MB12 responding child who doesnt have at least one parent who benefits

>from it as well.

>

>Then there is this recent discovery that has happened a few more times in

>the last couple

>of weeks. I have seen several adults who have been struggling with fungus

>try mB12 nasal

>spray and have had one of those dramatic responses that I commonly see.

>Two sisters felt

>fabulous, changed their lives, their mentality towards stress and anxiety

>and life. Really

>big effects... they clearly needed MB12.

>

>Then about a week later of using it they are both complaining of

>yeast-like symptoms.

>Mentally they felt great, but the infection is growing. They didn't want

>to give up MB12

>but felt it was causing the infection to grow.

>

>We have also seen parent reports say the same thing in the group.

>

>I have often thought about MB12 being killed off in people who need it. I

>have said that in

>the early days of this group. I wonder if there is an infection in these

>kids that end up

>killing propioni and the growth and death of propioni in a struggle to

>survive creates much

>excess propionic acid which in turn creates some of the symptoms of

>autism. Not in

>inborn error (which of course wouldn't grow from 1 in 10,000 to 1 in 150

>within 24 years),

>but an infection.

>

>However it happens, my belief is that many autisms are infections.

>Possibly an infection

>that commonly kills off the production of MB12 (maybe we should look for

>infections that

>coincide with high levels of cyanocobalamin)... anyway, an infection that

>literally feeds on

>the source of MB12 and starves the body of this amazing vitamin that helps

>it relax, detox,

>think clearly, process sensory input clearly, replecate DNA, fight viral

>infections, etc. It

>would be smart for an infection to kill MB12 because it would leave the

>body more

>vonerable for further infection and toxicity and stop DNA replication. If

>the war is microbe

>against human, this would be a great strategic move.

>

>Then of course in the mix is the oxalate connection and everything you say

>I don't doubt

>as well. ( I want you to see the asthma videos I have of kids asthma's

>going away from

>MB12. We need to collaborate ideas more because I am convinced that asthma

>is an

>infection and oxalate crystals lodged in the lungs... I see this

>relationship between MB12

>and oxalates)

>

>I'm just mixing in my view of the MB12 side of things.

>

>I strongly believe this is a multi-tier infection at work... possibly

>clostridia and/or virus

>and/or fungus and/or other with multi-tiered affects like the brain

>starving (the cortex

>and more) from a lack of MB12 and the biological warefare in the gut that

>kills off MB12

>also causing oxalates and related downstream damage.

>

>Please try to view this from a macro level, because if you get stuck in

>the micro you could

>criticize the banter but on a macro level I think it's darn pretty and

>it's been speaking to

>me for some time now.

>

>- Stan

>

> >

> > Listmates,

> >

> > The first article I've put below talks about using flagyl to reduce the

> > propionic acid produced by the flora in children with an inborn error of

> > metabolism. This defect involves losing the activity of an enzyme called

> > propionyl CoA carboxylase, which degrades propionic acid. There is no

> > suggestion in this article that any microbe is in an overgrowth situation,

> > but only that the normal amounts of propionic acid that is routinely

> > degraded by our human intestinal cells (which would have the enzyme defect

> > in these children) was not detoxifying normal amounts of propionic acid

> > coming from the flora.

> >

> > This study's data supplies strong evidence that propionic acid produced in

> > the gut is NOT mainly degraded by other microbes, but is instead

> reliant on

> > our own intestinal cells' performance. The enzyme that is defective is a

> > biotin-dependent enzyme and for that reason it is subject to loss of

> > function if oxalate gets into the active site. (See article on

> > transcarboxylase inhibition by oxalate below.)

> >

> > Flagyl, the drug they used to reduce the proprionic acid made by the

> flora,

> > and other antibiotics they tested also kills oxalobacter formigenes, which

> > is the oxalate-dependent microbe that we need to have in our flora because

> > it degrades the oxalate in the gut. Oxalate, of course, like propionic

> > acid, is another significant toxin. When oxalobacter is missing in the

> > gut, the oxalate that does not get degraded may impair the very same

> enzyme

> > that degrades propionic acid in intestinal cells because it is a

> > carboxylase.

> >

> > If you think about it, any delayed negative effect from flagyl that was

> > mediated by excesses of oxalate inhibiting propionyl CoA carboxylase would

> > not occur in these children whose enzyme was already totally knocked

> > out. You cannot worsen enzyme activity in someone who already has a

> > complete lack of activity. Even so, the oxalate that might not get

> > degraded after taking flagyl in these children might still knock out the

> > activity of other carboxylases, making flagyl perhaps a worrisome

> long-time

> > therapy because of its effect on oxalobacter formigenes. The article

> > investigating flagyl as a therapy for this inborn error advised

> > intermittent courses, because there was some lingering effect after the

> > flagyl was discontinued that made a constant exposure to the antimicrobial

> > unnecessary. Doesn't that sound familiar?

> >

> > In the light of the new article on propionic acid in autism that came out

> > this week, this interplay with flagyl could explain why some kids just

> keep

> > cycling between benefits on antimicrobial therapy and a loss of

> > improvements when the therapy is discontinued. In our DAN! community, a

> > specific set of symptoms have been labelled " clostridial " because of how

> > flagyl has lowered the quanitity of propionic family compounds on urinary

> > organic acid tests. Just as in these children with an inborn enzyme

> > defect, the problem with propionic acid may not represent overgrowth of

> any

> > microbe (except when there is other evidence of such overgrowth), but

> > instead could be a problem (as in these children with the inborn error) in

> > the handling of a normal toxic metabolite.

> >

> > Similarly, the problem with oxalates in many children may be HANDLING

> > issues caused by losing the one microbe that can degrade oxalate most

> > successfully. Maybe the better approach, compared to using an

> > antimicrobial that may kill our " friends " , is to restore the enzyme

> > activity that oxalate impaired by lowering oxalate in the diet and by

> using

> > other probiotics that less successfully degrade oxalate until Oxthera's

> > oxalobacter formigenes product is finally able to be purchased as a drug

> > about a year from now when their clinical trials are over.

> >

> > This information also puts a different slant on the parental observation

> > that going low oxalate has gotten some kids completely off the

> > antimicrobial merry-go-round. Now, doesn't it make sense why this good

> > news happened? These fortunate children would be expected to have been

> > those whose troubles caused by propionic acid (and related compounds)

> > stemmed from the excess oxalate in their gut affecting the performance of

> > carboxylase enzymes that are functioning in their own intestinal cells,

> and

> > perhaps affecting other carboxylases functioning in other organs.

> >

> > Please do read the abstracts below for clarification.

> >

> > 1: Arch Dis Child. 2000 Feb;82(2):169-72.Links

> >

> > Effect of oral antibiotics on intestinal production of propionic acid.

> >

> > Mellon AF, Deshpande SA, Mathers JC, Bartlett K.

> >

> > Sir Spence Institute of Child Health, Royal Infirmary,

> Queen

> > Road, Newcastle upon Tyne NE1 4LP, UK.

> >

> > BACKGROUND: Propionic acid derived from colonic bacterial fermentation

> > contributes substantially to overall propionate load in children with

> > disorders of propionate metabolism, and its reduction is important for

> > adequate metabolic control. AIMS: To evaluate the in vitro and in vivo

> > effects of antibiotic treatment on propionate production by colonic

> > bacteria, and plasma propionate concentrations in a child with propionic

> > acidaemia. METHODS: In vitro fermentation techniques were used to study

> the

> > effects of addition of antibiotics (metronidazole, clindamycin,

> > erythromycin, and vancomycin) on net faecal production of short chain

> fatty

> > acids including propionic acid. Courses of oral antibiotics of 7 days

> > duration were used to assess the in vivo effects on faecal propionate

> > production and metabolic control including plasma propionate

> > concentrations. RESULTS: Metronidazole produced the largest and most

> > consistent reduction (77-84%) in the production in vitro of propionate

> from

> > faecal homogenates. Oral administration of metronidazole reduced faecal

> > propionate production by 43% within 24 hours of treatment; a 7 day course

> > virtually eliminated it for the next 3 weeks. These reductions were

> > accompanied by substantially lowered plasma propionate concentrations

> > during the same period. CONCLUSIONS: Intermittent courses of oral

> > metronidazole might be as effective as continuous treatment in reducing

> gut

> > propionate production in children with disorders of propionate metabolism.

> >

> > PMID: 10648377 [PubMed - indexed for MEDLINE]

> >

> > Eur J Pediatr. 1998 Jan;157(1):50-2.[] Links

> >

> > An unusual late-onset case of propionic acidaemia: biochemical

> > investigations, neuroradiological findings and mutation analysis.

> >

> > Pérez-Cerdá C, Merinero B, Martí M, Cabrera JC, Peña L, García MJ,

> Gangoiti

> > J, Sanz P, Rodríguez-Pombo P, Hoenicka J, E, Muro S, Ugarte M.

> >

> > Centro de Diagnóstico de Enfermedades Moleculares, Department of Molecular

> > Biology, CBMSO, Facultad de Ciencias, Universidad Autónoma de Madrid,

> Spain.

> >

> > We report a 5-year-old boy with propionic acidaemia who developed a

> rapidly

> > fatal necrosis of the basal ganglia after an episode of clinical

> > deterioration. Neither metabolic acidosis nor hyperammonaemia were

> present.

> > Organic acid analysis in both urine and CSF showed increased levels of

> > methylcitric and 3-hydroxypropionic acids. Propionic acidaemia was

> > confirmed by demonstrating a propionyl-CoA carboxylase deficiency (11% of

> > control value) in skin fibroblasts. DNA analysis revealed that the patient

> > was a compound heterozygote for two mutations in the PCCB gene.

> CONCLUSION:

> > Propionic acidaemia can present as a sudden and fatal neurological disease

> > and not only as an organic aciduria with severe biochemical dis-turbances

> > and progressive neurological deterioration.

> >

> > PMID: 9461363 [PubMed - indexed for MEDLINE]

> >

> > >J Biol Chem. 1969 Nov 10;244(21):5820-7.Related Articles, Links

> > >[]

> > >Transcarboxylase. VII. Exchange reactions and kinetics of oxalate

> inhibition.

> > >

> > >Northrop DB, Wood HG.

> > >

> > >PMID: 5350938 [PubMed - indexed for MEDLINE]

> >

> > Appl Environ Microbiol. 2002 August; 68(8): 3841–3847.

> > Oxalobacter formigenes and Its Potential Role in Human Health

> > Sylvia H. Duncan,1 J. ,1 Poonam Kaul,2 Ross P. Holmes,3

> > Milton J. ,4 and Colin S. 1*

> >

>

<http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=124017>http://www.pub\

medcentral.nih.gov/articlerender.fcgi?artid=124017

> >

> > Oxalate degradation by the anaerobic bacterium Oxalobacter formigenes is

> > important for human health, helping to prevent hyperoxaluria and disorders

> > such as the development of kidney stones. Oxalate-degrading activity

> cannot

> > be detected in the gut flora of some individuals, possibly because

> > Oxalobacter is susceptible to commonly used antimicrobials. Here,

> > clarithromycin, doxycycline, and some other antibiotics inhibited oxalate

> > degradation by two human strains of O. formigenes. These strains varied in

> > their response to gut environmental factors, including exposure to gastric

> > acidity and bile salts. O. formigenes strains established oxalate

> breakdown

> > in fermentors which were preinoculated with fecal bacteria from

> individuals

> > lacking oxalate-degrading activity. Reducing the concentration of oxalate

> > in the medium reduced the numbers of O. formigenes bacteria. Oxalate

> > degradation was established and maintained at dilution rates comparable to

> > colonic transit times in healthy individuals. A single oral ingestion

> of O.

> > formigenes by adult volunteers was, for the first time, shown to result in

> > (i) reduced urinary oxalate excretion following administration of an

> > oxalate load, (ii) the recovery of oxalate-degrading activity in feces,

> and

> > (iii) prolonged retention of colonization.

> >

> > 3: J Endourol. 2005 Jan-Feb;19(1):102-6.

> >

> > Effect of antibiotics on Oxalobacter formigenes colonization of human

> > gastrointestinal tract.

> >

> > Mittal RD, Kumar R, Bid HK, Mittal B.

> >

> > Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical

> > Sciences,

> > Lucknow, India. ramamittal@...

> >

> > BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing

> in the

> > human gastrointestinal tract that degrades oxalate and reduces its

> availability

> > for absorption. This bacterium is assumed to be antibiotic sensitive, and

> > repeated antibiotic therapies could eradicate it. The aim of the

> present study

> > was to determine the differences in the colonization by O. formigenes of

> > individuals who had been on antibiotics for at least 5 days at the time of

> > sample

> > collection and individuals who had not taken antibiotics for at least 3

> months.

> > PATIENTS AND METHODS: Stool samples were collected from 80 individuals

> without

> > stone disease (35 with and 45 without antibiotic consumption) and 100

> patients

> > with stone disease (20 with and 80 without antibiotic consumption).

> Oxalobacter

> > formigenes was detected by a polymerase chain reaction-based method,

> and the

> > presence/absence of O. formigenes was correlated with urinary oxalate

> > concentrations. RESULTS: Lower percentages of individuals without stone

> disease

> > and with stone disease who were consuming antibiotics had O. formigenes

> > colonization than individuals without antibiotic consumption. Urinary

> oxalate

> > concentrations were higher in the individuals without O. formigenes than in

> > colonized individuals. CONCLUSION: Our observations confirm a direct

> > association

> > between antibiotic consumption and absence of O. formigenes. Absence of

> > intestinal O. formigenes could represent a pathogenic factor in calcium

> oxalate

> > urolithiasis when antibiotics are prescribed generously.

> >

> > Publication Types:

> > Comparative Study

> >

> > PMID: 15735393 [PubMed - indexed for MEDLINE]

> >

> > J Endourol. 2005 Jan-Feb;19(1):102-6.[] Links

> >

> > Effect of antibiotics on Oxalobacter formigenes colonization of human

> > gastrointestinal tract.

> >

> > Mittal RD, Kumar R, Bid HK, Mittal B.

> >

> > Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical

> > Sciences, Lucknow, India. ramamittal@...

> >

> > BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in

> > the human gastrointestinal tract that degrades oxalate and reduces its

> > availability for absorption. This bacterium is assumed to be antibiotic

> > sensitive, and repeated antibiotic therapies could eradicate it. The

> aim of

> > the present study was to determine the differences in the colonization by

> > O. formigenes of individuals who had been on antibiotics for at least 5

> > days at the time of sample collection and individuals who had not taken

> > antibiotics for at least 3 months. PATIENTS AND METHODS: Stool samples

> were

> > collected from 80 individuals without stone disease (35 with and 45

> without

> > antibiotic consumption) and 100 patients with stone disease (20 with

> and 80

> > without antibiotic consumption). Oxalobacter formigenes was detected by a

> > polymerase chain reaction-based method, and the presence/absence of O.

> > formigenes was correlated with urinary oxalate concentrations. RESULTS:

> > Lower percentages of individuals without stone disease and with stone

> > disease who were consuming antibiotics had O. formigenes colonization than

> > individuals without antibiotic consumption. Urinary oxalate concentrations

> > were higher in the individuals without O. formigenes than in colonized

> > individuals. CONCLUSION: Our observations confirm a direct association

> > between antibiotic consumption and absence of O. formigenes. Absence of

> > intestinal O. formigenes could represent a pathogenic factor in calcium

> > oxalate urolithiasis when antibiotics are prescribed generously.

> >

> > PMID: 15735393 [PubMed - indexed for MEDLINE]

> >

> > MacFabe 2007 Intraventricular propionic acid & possible role in autism.pdf

> >

> > Behav Brain Res. 2007 Jan 10;176(1):149-69. Epub 2006 Sep 1.[] Links

> >

> > Neurobiological effects of intraventricular propionic acid in rats:

> > possible role of short chain fatty acids on the pathogenesis and

> > characteristics of autism spectrum disorders.

> >

> > MacFabe DF, Cain DP, -Capote K, lin AE, Hoffman JE, Boon F,

> > AR, Kavaliers M, Ossenkopp KP.

> >

> > The Kilee Patchell- Autism Research Group, Department of Psychology,

> > Division of Developmental Disabilities, University of Western Ontario,

> > Social Science Centre, London, Canada. dmacfabe@...

> >

> > Clinical observations suggest that certain gut and dietary factors may

> > transiently worsen symptoms in autism spectrum disorders (ASD), epilepsy

> > and some inheritable metabolic disorders. Propionic acid (PPA) is a short

> > chain fatty acid and an important intermediate of cellular metabolism. PPA

> > is also a by-product of a subpopulation of human gut enterobacteria and is

> > a common food preservative. We examined the behavioural,

> > electrophysiological, neuropathological, and biochemical effects of

> > treatment with PPA and related compounds in adult rats. Intraventricular

> > infusions of PPA produced reversible repetitive dystonic behaviours,

> > hyperactivity, turning behaviour, retropulsion, caudate spiking, and the

> > progressive development of limbic kindled seizures, suggesting that this

> > compound has central effects. Biochemical analyses of brain homogenates

> > from PPA treated rats showed an increase in oxidative stress markers

> (e.g.,

> > lipid peroxidation and protein carbonylation) and glutathione

> S-transferase

> > activity coupled with a decrease in glutathione and glutathione peroxidase

> > activity. Neurohistological examinations of hippocampus and adjacent white

> > matter (external capsule) of PPA treated rats revealed increased reactive

> > astrogliosis (GFAP immunoreactivity) and activated microglia (CD68

> > immunoreactivity) suggestive of a neuroinflammatory process. This was

> > coupled with a lack of cytotoxicity (cell counts, cleaved caspase 3'

> > immunoreactivity), and an increase in phosphorylated CREB

> immunoreactivity.

> > We propose that some types of autism may be partial forms of genetically

> > inherited or acquired disorders involving altered PPA metabolism. Thus,

> > intraventricular administration of PPA in rats may provide a means to

> model

> > some aspects of human ASD in rats.

> >

> > PMID: 16950524 [PubMed - indexed for MEDLINE]

> >

> > --

> > Internal Virus Database is out-of-date.

> > Checked by AVG Free Edition.

> > Version: 7.5.484 / Virus Database: 269.12.0/957 - Release Date:

> 8/16/2007 1:46 PM

> >

>

>~ Bloom Where You're Planted ~

>

--

Internal Virus Database is out-of-date.

Checked by AVG Free Edition.

Version: 7.5.484 / Virus Database: 269.12.0/957 - Release Date: 8/16/2007 1:46

PM

October 6, 2007

Kathy,

I couldn't find that, but I did find this that makes it sound like fluoride

helps to promote the formation of stones.

J Nutr. 1982 Sep;112(9):1787-95.[] Links

Role of fluoride in formation of urinary calculi: studies in rats.

Anasuya A.

The effect of fluoride on urinary calculi formation in young rats was

investigated. Two studies, in which rats received diets that included

either higher calcium (9 g/kg diet) or normal clacium (5 g/kg diet), were

conducted At each level of calcium, one group of rats received a high level

of fluoride and another a low level of fluoride in the diet. Rats ingesting

high fluoride diets exhibited a higher incidence of crystalluria and

bladder stones compared with those receiving low fluoride diets. However,

compared with higher calcium diets, normal calcium diets delayed the

appearance of crystalluria and produced smaller calculi. Calcium and

oxalate were the major components of the calculi. Calculi of rats fed the

higher calcium and high fluoride diet contained relatively less protein and

more calcium compared with calculi formed in rats ingesting the higher

calcium and low fluoride diet. The concentration of fluoride in calculi

from rats fed high fluoride diets was significantly higher than that of

calculi from rats fed low fluoride diets. A significant positive

correlation between calcium and fluoride concentration of calculi was

observed in rats fed the higher calcium diet only. These studies indicate

that ingestion of excess fluoride facilities calcium oxalate crystalluria

and promotes the formation of bladder stones in rats, under the

experimental conditions used.

PMID: 7108643 [PubMed - indexed for MEDLINE]

At 08:25 PM 10/5/2007, you wrote:

>?

>

>Remember I forwarded you with out the URL about FLUORIDE dedgradating

>oxylbacter forminges? I know that DIFLUCAN has a FLUORINE molecule in it,

>does FLAGYL too? This I don't know and can't find on any google search?

>-------------------------------------------------------------------------------\

--------------------------------------------------------------------------------

>

>Fluoride Template

>Fluoride has even been shown to affect the pituitary gland, .... contain

>fluoride: Prozac (fluoxetine), Rohypnol (flunitrazepam), Diflucan

>(fluconazole, ...

>www.bcd.com.au/FluorideDocs/PoisoningSYmpts.htm - 27k - Cached - Similar

>pages - Note this

>-------------------------------------------------------------------------------\

------------------------------------------------------------------------------

>

>http://www.level1diet.com/research/id/1274424

>-------------------------------------------------------------------------------\

----------------------------------------------------------------------------

>

>http://www.rense.com/general60/nationalflouridedatabase.htm

>One must also look at the growing number of fluorinated pharmaceutical

>products that have been widely prescribed, including,

> but certainly not limited to: Lariam, Cipro (ciprofloxacin), Crestor,

> Flonase, Lipitor, Luvox, Diflucan, Lexapro, Paxil, Lescol,

> Prozac, Stelazine, Haldol, Levaquin (levofloxacin), Celexa, Celebrex,

> Prevacid, Zagam, Tequin, Halfan, Propulsid, Advair Diskus,

>Flovent, Baycol, Avelox, Redux, Trovan, Casodex

> and so on. Some of the above named pharmaceuticals have already been

> removed from the market due to side effects.

>-------------------------------------------------------------------------------\

----------------------------------------------------------------------------

>

>http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6SYP-4KSVFTV-2 & _user=\

10 & _coverDate=01%2F10%2F2007 & _rdoc=1 & _fmt= & _orig=search & _sort=d & view=c & _acct=C00\

0050221 & _version=1 & _urlVersion=0 & _userid=10 & md5=23811a872a8b7d3f1620d7eeeb2219f2

>

>-------------------------------------------------------------------------------\

--------------------------------------------------------------------------------

>

>It is also interesting that ingesting fluoride all the time wipes out your

>B-6 Vitamin and Enzyme activity, which would make the oxalate formation

>more easy in the body right?

>per ........ Twelve male Wistar rats were randomized to two groups and

>were fed either a standard diet or a vitamin-B6-deficient diet for 3

>weeks. Then the animals received an intravenous infusion of 100 mg/ml

>(960.6 mumol/ml) of hydroxypyruvate slowly over 10 min. Urine samples were

>collected just before hydroxypyruvate infusion and at hourly intervals

>until 5 h afterward. Urinary oxalate, glycolate, and citrate levels were

>measured by capillary ... Read More »

>» Published in Urol Res. 2007 Jun 13;

>-------------------------------------------------------------------------------\

--------------------------------------------------------------------------

>Could the epidemic of autism also be blamed on poisoning our children

>slowly with FLUORIDE/Drugs containing often used in autism population that

>contain Fluoride, degradating enzymes in the gut further, and flora that

>then produces all these nasty neurotoxic stews?

>

> Flagyl and an inborn error of metabolism: important

>implications!

>

>Listmates,

>

>The first article I've put below talks about using flagyl to reduce the

>propionic acid produced by the flora in children with an inborn error of

>metabolism. This defect involves losing the activity of an enzyme called

>propionyl CoA carboxylase, which degrades propionic acid. There is no

>suggestion in this article that any microbe is in an overgrowth situation,

>but only that the normal amounts of propionic acid that is routinely

>degraded by our human intestinal cells (which would have the enzyme defect

>in these children) was not detoxifying normal amounts of propionic acid

>coming from the flora.

>

>This study's data supplies strong evidence that propionic acid produced in

>the gut is NOT mainly degraded by other microbes, but is instead reliant on

>our own intestinal cells' performance. The enzyme that is defective is a

>biotin-dependent enzyme and for that reason it is subject to loss of

>function if oxalate gets into the active site. (See article on

>transcarboxylase inhibition by oxalate below.)

>

>Flagyl, the drug they used to reduce the proprionic acid made by the flora,

>and other antibiotics they tested also kills oxalobacter formigenes, which

>is the oxalate-dependent microbe that we need to have in our flora because

>it degrades the oxalate in the gut. Oxalate, of course, like propionic

>acid, is another significant toxin. When oxalobacter is missing in the

>gut, the oxalate that does not get degraded may impair the very same enzyme

>that degrades propionic acid in intestinal cells because it is a

>carboxylase.

>

>If you think about it, any delayed negative effect from flagyl that was

>mediated by excesses of oxalate inhibiting propionyl CoA carboxylase would

>not occur in these children whose enzyme was already totally knocked

>out. You cannot worsen enzyme activity in someone who already has a

>complete lack of activity. Even so, the oxalate that might not get

>degraded after taking flagyl in these children might still knock out the

>activity of other carboxylases, making flagyl perhaps a worrisome long-time

>therapy because of its effect on oxalobacter formigenes. The article

>investigating flagyl as a therapy for this inborn error advised

>intermittent courses, because there was some lingering effect after the

>flagyl was discontinued that made a constant exposure to the antimicrobial

>unnecessary. Doesn't that sound familiar?

>

>In the light of the new article on propionic acid in autism that came out

>this week, this interplay with flagyl could explain why some kids just keep

>cycling between benefits on antimicrobial therapy and a loss of

>improvements when the therapy is discontinued. In our DAN! community, a

>specific set of symptoms have been labelled " clostridial " because of how

>flagyl has lowered the quanitity of propionic family compounds on urinary

>organic acid tests. Just as in these children with an inborn enzyme

>defect, the problem with propionic acid may not represent overgrowth of any

>microbe (except when there is other evidence of such overgrowth), but

>instead could be a problem (as in these children with the inborn error) in

>the handling of a normal toxic metabolite.

>

>Similarly, the problem with oxalates in many children may be HANDLING

>issues caused by losing the one microbe that can degrade oxalate most

>successfully. Maybe the better approach, compared to using an

>antimicrobial that may kill our " friends " , is to restore the enzyme

>activity that oxalate impaired by lowering oxalate in the diet and by using

>other probiotics that less successfully degrade oxalate until Oxthera's

>oxalobacter formigenes product is finally able to be purchased as a drug

>about a year from now when their clinical trials are over.

>

>This information also puts a different slant on the parental observation

>that going low oxalate has gotten some kids completely off the

>antimicrobial merry-go-round. Now, doesn't it make sense why this good

>news happened? These fortunate children would be expected to have been

>those whose troubles caused by propionic acid (and related compounds)

>stemmed from the excess oxalate in their gut affecting the performance of

>carboxylase enzymes that are functioning in their own intestinal cells, and

>perhaps affecting other carboxylases functioning in other organs.

>

>Please do read the abstracts below for clarification.

>

>1: Arch Dis Child. 2000 Feb;82(2):169-72.Links

>

>Effect of oral antibiotics on intestinal production of propionic acid.

>

>Mellon AF, Deshpande SA, Mathers JC, Bartlett K.

>

>Sir Spence Institute of Child Health, Royal Infirmary, Queen

> Road, Newcastle upon Tyne NE1 4LP, UK.

>

>BACKGROUND: Propionic acid derived from colonic bacterial fermentation

>contributes substantially to overall propionate load in children with

>disorders of propionate metabolism, and its reduction is important for

>adequate metabolic control. AIMS: To evaluate the in vitro and in vivo

>effects of antibiotic treatment on propionate production by colonic

>bacteria, and plasma propionate concentrations in a child with propionic

>acidaemia. METHODS: In vitro fermentation techniques were used to study the

>effects of addition of antibiotics (metronidazole, clindamycin,

>erythromycin, and vancomycin) on net faecal production of short chain fatty

>acids including propionic acid. Courses of oral antibiotics of 7 days

>duration were used to assess the in vivo effects on faecal propionate

>production and metabolic control including plasma propionate

>concentrations. RESULTS: Metronidazole produced the largest and most

>consistent reduction (77-84%) in the production in vitro of propionate from

>faecal homogenates. Oral administration of metronidazole reduced faecal

>propionate production by 43% within 24 hours of treatment; a 7 day course

>virtually eliminated it for the next 3 weeks. These reductions were

>accompanied by substantially lowered plasma propionate concentrations

>during the same period. CONCLUSIONS: Intermittent courses of oral

>metronidazole might be as effective as continuous treatment in reducing gut

>propionate production in children with disorders of propionate metabolism.

>

>PMID: 10648377 [PubMed - indexed for MEDLINE]

>

>Eur J Pediatr. 1998 Jan;157(1):50-2.[] Links

>

>An unusual late-onset case of propionic acidaemia: biochemical

>investigations, neuroradiological findings and mutation analysis.

>

>Pérez-Cerdá C, Merinero B, Martí M, Cabrera JC, Peña L, García MJ, Gangoiti

>J, Sanz P, Rodríguez-Pombo P, Hoenicka J, E, Muro S, Ugarte M.

>

>Centro de Diagnóstico de Enfermedades Moleculares, Department of Molecular

>Biology, CBMSO, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.

>

>We report a 5-year-old boy with propionic acidaemia who developed a rapidly

>fatal necrosis of the basal ganglia after an episode of clinical

>deterioration. Neither metabolic acidosis nor hyperammonaemia were present.

>Organic acid analysis in both urine and CSF showed increased levels of

>methylcitric and 3-hydroxypropionic acids. Propionic acidaemia was

>confirmed by demonstrating a propionyl-CoA carboxylase deficiency (11% of

>control value) in skin fibroblasts. DNA analysis revealed that the patient

>was a compound heterozygote for two mutations in the PCCB gene. CONCLUSION:

>Propionic acidaemia can present as a sudden and fatal neurological disease

>and not only as an organic aciduria with severe biochemical dis-turbances

>and progressive neurological deterioration.

>

>PMID: 9461363 [PubMed - indexed for MEDLINE]

>

> >J Biol Chem. 1969 Nov 10;244(21):5820-7.Related Articles, Links

> >[]

> >Transcarboxylase. VII. Exchange reactions and kinetics of oxalate

> inhibition.

> >

> >Northrop DB, Wood HG.

> >

> >PMID: 5350938 [PubMed - indexed for MEDLINE]

>

>Appl Environ Microbiol. 2002 August; 68(8): 3841-3847.

>Oxalobacter formigenes and Its Potential Role in Human Health

>Sylvia H. Duncan,1 J. ,1 Poonam Kaul,2 Ross P. Holmes,3

>Milton J. ,4 and Colin S. 1*

>

>http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=124017

>

>Oxalate degradation by the anaerobic bacterium Oxalobacter formigenes is

>important for human health, helping to prevent hyperoxaluria and disorders

>such as the development of kidney stones. Oxalate-degrading activity cannot

>be detected in the gut flora of some individuals, possibly because

>Oxalobacter is susceptible to commonly used antimicrobials. Here,

>clarithromycin, doxycycline, and some other antibiotics inhibited oxalate

>degradation by two human strains of O. formigenes. These strains varied in

>their response to gut environmental factors, including exposure to gastric

>acidity and bile salts. O. formigenes strains established oxalate breakdown

>in fermentors which were preinoculated with fecal bacteria from individuals

>lacking oxalate-degrading activity. Reducing the concentration of oxalate

>in the medium reduced the numbers of O. formigenes bacteria. Oxalate

>degradation was established and maintained at dilution rates comparable to

>colonic transit times in healthy individuals. A single oral ingestion of O.

>formigenes by adult volunteers was, for the first time, shown to result in

>(i) reduced urinary oxalate excretion following administration of an

>oxalate load, (ii) the recovery of oxalate-degrading activity in feces, and

>(iii) prolonged retention of colonization.

>

>3: J Endourol. 2005 Jan-Feb;19(1):102-6.

>

>Effect of antibiotics on Oxalobacter formigenes colonization of human

>gastrointestinal tract.

>

>Mittal RD, Kumar R, Bid HK, Mittal B.

>

>Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical

>Sciences,

>Lucknow, India. ramamittal@...

>

>BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in the

>human gastrointestinal tract that degrades oxalate and reduces its

>availability

>for absorption. This bacterium is assumed to be antibiotic sensitive, and

>repeated antibiotic therapies could eradicate it. The aim of the present study

>was to determine the differences in the colonization by O. formigenes of

>individuals who had been on antibiotics for at least 5 days at the time of

>sample

>collection and individuals who had not taken antibiotics for at least 3

>months.

>PATIENTS AND METHODS: Stool samples were collected from 80 individuals without

>stone disease (35 with and 45 without antibiotic consumption) and 100 patients

>with stone disease (20 with and 80 without antibiotic consumption).

>Oxalobacter

>formigenes was detected by a polymerase chain reaction-based method, and the

>presence/absence of O. formigenes was correlated with urinary oxalate

>concentrations. RESULTS: Lower percentages of individuals without stone

>disease

>and with stone disease who were consuming antibiotics had O. formigenes

>colonization than individuals without antibiotic consumption. Urinary oxalate

>concentrations were higher in the individuals without O. formigenes than in

>colonized individuals. CONCLUSION: Our observations confirm a direct

>association

>between antibiotic consumption and absence of O. formigenes. Absence of

>intestinal O. formigenes could represent a pathogenic factor in calcium

>oxalate

>urolithiasis when antibiotics are prescribed generously.

>

>Publication Types:

>Comparative Study

>

>PMID: 15735393 [PubMed - indexed for MEDLINE]

>

>J Endourol. 2005 Jan-Feb;19(1):102-6.[] Links

>

>Effect of antibiotics on Oxalobacter formigenes colonization of human

>gastrointestinal tract.

>

>Mittal RD, Kumar R, Bid HK, Mittal B.

>

>Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical

>Sciences, Lucknow, India. ramamittal@...

>

>BACKGROUND AND PURPOSE: Oxalobacter formigenes is a bacterium residing in

>the human gastrointestinal tract that degrades oxalate and reduces its

>availability for absorption. This bacterium is assumed to be antibiotic

>sensitive, and repeated antibiotic therapies could eradicate it. The aim of

>the present study was to determine the differences in the colonization by

>O. formigenes of individuals who had been on antibiotics for at least 5

>days at the time of sample collection and individuals who had not taken

>antibiotics for at least 3 months. PATIENTS AND METHODS: Stool samples were

>collected from 80 individuals without stone disease (35 with and 45 without

>antibiotic consumption) and 100 patients with stone disease (20 with and 80

>without antibiotic consumption). Oxalobacter formigenes was detected by a

>polymerase chain reaction-based method, and the presence/absence of O.

>formigenes was correlated with urinary oxalate concentrations. RESULTS:

>Lower percentages of individuals without stone disease and with stone

>disease who were consuming antibiotics had O. formigenes colonization than

>individuals without antibiotic consumption. Urinary oxalate concentrations

>were higher in the individuals without O. formigenes than in colonized

>individuals. CONCLUSION: Our observations confirm a direct association

>between antibiotic consumption and absence of O. formigenes. Absence of

>intestinal O. formigenes could represent a pathogenic factor in calcium

>oxalate urolithiasis when antibiotics are prescribed generously.

>

>PMID: 15735393 [PubMed - indexed for MEDLINE]

>

>MacFabe 2007 Intraventricular propionic acid & possible role in autism.pdf

>

>Behav Brain Res. 2007 Jan 10;176(1):149-69. Epub 2006 Sep 1.[] Links

>

>Neurobiological effects of intraventricular propionic acid in rats:

>possible role of short chain fatty acids on the pathogenesis and

>characteristics of autism spectrum disorders.

>

>MacFabe DF, Cain DP, -Capote K, lin AE, Hoffman JE, Boon F,

> AR, Kavaliers M, Ossenkopp KP.

>

>The Kilee Patchell- Autism Research Group, Department of Psychology,

>Division of Developmental Disabilities, University of Western Ontario,

>Social Science Centre, London, Canada. dmacfabe@...

>

>Clinical observations suggest that certain gut and dietary factors may

>transiently worsen symptoms in autism spectrum disorders (ASD), epilepsy

>and some inheritable metabolic disorders. Propionic acid (PPA) is a short

>chain fatty acid and an important intermediate of cellular metabolism. PPA

>is also a by-product of a subpopulation of human gut enterobacteria and is

>a common food preservative. We examined the behavioural,

>electrophysiological, neuropathological, and biochemical effects of

>treatment with PPA and related compounds in adult rats. Intraventricular

>infusions of PPA produced reversible repetitive dystonic behaviours,

>hyperactivity, turning behaviour, retropulsion, caudate spiking, and the

>progressive development of limbic kindled seizures, suggesting that this

>compound has central effects. Biochemical analyses of brain homogenates

>from PPA treated rats showed an increase in oxidative stress markers (e.g.,

>lipid peroxidation and protein carbonylation) and glutathione S-transferase

>activity coupled with a decrease in glutathione and glutathione peroxidase

>activity. Neurohistological examinations of hippocampus and adjacent white

>matter (external capsule) of PPA treated rats revealed increased reactive

>astrogliosis (GFAP immunoreactivity) and activated microglia (CD68

>immunoreactivity) suggestive of a neuroinflammatory process. This was

>coupled with a lack of cytotoxicity (cell counts, cleaved caspase 3'

>immunoreactivity), and an increase in phosphorylated CREB immunoreactivity.

>We propose that some types of autism may be partial forms of genetically

>inherited or acquired disorders involving altered PPA metabolism. Thus,

>intraventricular administration of PPA in rats may provide a means to model

>some aspects of human ASD in rats.

>

>PMID: 16950524 [PubMed - indexed for MEDLINE]

>

>--

>Internal Virus Database is out-of-date.

>Checked by AVG Free Edition.

>Version: 7.5.484 / Virus Database: 269.12.0/957 - Release Date: 8/16/2007

>1:46 PM

>

--

Internal Virus Database is out-of-date.

Checked by AVG Free Edition.

Version: 7.5.484 / Virus Database: 269.12.0/957 - Release Date: 8/16/2007 1:46

PM

October 6, 2007

The only one I've found is by Rio Health brand, they call it Quebra Pedra (other common names for the herb are Chanca Piedra, Stone Breaker, Pitirishi, Shatter Stone, Quinina Criolla, Hurricane Weed)http://www.riohealth.co.uk/product.asp?product_name=QP090 & gclid=COGv54fq5IUCFThBEgodHTi0RAI don't have any full text papers on it, apart from the one at the bottom of original post, which is free access.Interestingly enough the herb appears to have some antiinflammatory and antiviral effects too.... as well as being hepatoprotective and an antioxidantPathophysiology. 2007 Oct 1; [Epub ahead of print]Hepatocytes are protected by herb Phyllanthus niruri protein isolate against thioacetamide toxicity.Sarkar MK...Department of Chemistry, Bose Institute, 93/1, Acharya Prafulla Chandra Road, Kolkata 700009, West Bengal, India.The

herb, Phyllanthus niruri has been known to possess protective activity

against various drugs and toxins induced hepatic disorders. Present

study was conducted to evaluate the role of the protein isolate of the

herb against thioacetamide (TAA)-induced cytotoxicity in mice

hepatocytes. In vitro cell viability, lactate dehydrogenase (LDH) and

alanine amino transferase (ALT) leakage were measured as the indicators

of cell damage. In addition, measurement of the level of non-protein

thiol, glutathione (GSH); activities of the antioxidant enzymes,

superoxide dismutase (SOD), catalase (CAT) and glutathione

S-transferase (GST) as well as the extent of lipid peroxidation were

carried out to evaluate the prooxidant-antioxidant status of the cell.

2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was

performed to determine the radical scavenging activity of the protein

isolate. Results showed that the administration of the protein isolate

prior to TAA exposure significantly reduced the release of LDH and ALT

leakage and enhanced the cell viability in a dose-dependent manner in

hepatocytes. Besides, the protein isolate appeared to prevent the

alterations in GSH levels and activities of the anti-oxidant enzymes

related to prooxidant-antioxidant status of hepatocytes. It also

reduced the TAA-induced lipid peroxidation significantly as

demonstrated by the reduction of malondialdehyde (MDA) production. DPPH

radical scavenging assay showed that the protein isolate possessed

radical scavenging activity. Combining, the data suggest that the

protein isolate could protect hepatocytes from TAA-induced cellular

injury probably by its antioxidative and radical scavenging properties.PMID: 17913477 [PubMed - as supplied by publisher]2: Southeast Asian J Trop Med Public Health. 2007 Jul;38(4):609-15.Related Articles, LinksIn

vitro and in vivo antiplasmodial activity and cytotoxicity of extracts

of Phyllanthus niruri L. herbs traditionally used to treat malaria in

Indonesia.Mustofa...Department

of Pharmacology and Toxicology, Faculty of Medicine, Gadjah Mada

University, Yogyakarta, Indonesia. mustofajogja@...In

endemic areas where malaria is prevalent, medicinal plants are often

used to treat malaria. This study was conducted to evaluate the in

vitro and in vivo antiplasmodial activity and cytotoxicity of extracts

of meniran (Phyllanthus niruri L.) herb traditionally used to treat

malaria in Indonesia. Three extracts viz aqueous, methanolic and

chloroformic extracts were obtained by maceration of the herbs. A

radioactive method was used to evaluate the in vitro antiplasmodial

activity of the extracts on chloroquine-resistant (FCR-3) and

chloroquine-sensitive (D-10) strains of Plasmodium falciparum. In vitro

antiplasmodial activity was expressed by the concentration inhibiting

50% of parasite growth (IC50). Cytotoxicity was estimated on Hela cells

and the Cytotoxicity Index (CI = IC50 on HeLa cells/IC50 on FCR-3

strain) was calculated to evaluate the safety of tested extracts. A

standard 4-day test on P berghei infected mice was used to evaluate the

in vivo antiplasmodial activity of the extracts showing strong in vitro

antiplasmodial activity, for both the methanolic and aqueous extracts.

The in vivo antiplasmodial activity was expressed by the dose

inhibiting 50% of parasite growth (ED50). The IC50 values obtained for

these extracts against P. falciparum ranged from 2.3 to 202.4

microg/ml. The methanolic extract was the most active in vitro extract

with an IC50 that ranged from 2.3 to 3.9 microg/ml and a CI that ranged

from 41.3 to 57.5. This was also the most in vivo active extract with

an ED50 of 9.1 mg/kg/d. Further study will be conducted to isolate and

purify active compounds presented in the methanolic extract.Publication Types: Research Support, Non-U.S. Gov'tPMID: 17882995 [PubMed - in process]3: J Pharm Pharmacol. 2006 Dec;58(12):1559-70. Phytochemicals from Phyllanthus niruri Linn. and their pharmacological properties: a review.Bagalkotkar ...Department of Biomedical Sciences, University Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.This

review discusses the medicinal plant Phyllanthus niruri Linn.

(Euphorbiaceae), its wide variety of phytochemicals and their

pharmacological properties. The active phytochemicals, flavonoids,

alkaloids, terpenoids, lignans, polyphenols, tannins, coumarins and

saponins, have been identified from various parts of P. niruri.

Extracts of this herb have been proven to have therapeutic effects in

many clinical studies. Some of the most intriguing therapeutic

properties include anti-hepatotoxic, anti-lithic, anti-hypertensive,

anti-HIV and anti-hepatitis B. Therefore, studies relating to chemical

characteristics and structural properties of the bioactive

phytochemicals found in P. niruri are very useful for further research

on this plant as many of the phytochemicals have shown preclinical

therapeutic efficacies for a wide range of human diseases, including

HIV/AIDS and hepatitis B.Publication Types: ReviewPMID: 17331318 [PubMed - indexed for MEDLINE]4: Biol Pharm Bull. 2007 Feb;30(2):382-4. Inhibitory effects of methyl brevifolincarboxylate isolated from Phyllanthus niruri L. on platelet aggregation.Iizuka T..Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan. iizuka@...A

platelet-aggregatory inhibitor was isolated from the 50% MeOH extract

of Phyllanthus niruri L. leaf. Its structure was determined to be

methyl brevifolincarboxylate on the basis of the 1H-, 13C-NMR, and

high-resolution mass spectral data. We compared the antiplatelet

aggregatory effects of the constituent with adenosine, a well-known

inhibitor of platelet aggregation. Platelet aggregation was induced by

collagen or adenosine 5'-diphosphate as an activating agent; the extent

of inhibition was monitored with a platelet aggregometer employing a

laser-scattering method. The inhibitory effects of methyl

brevifolincarboxylate were found to be as potent as adenosine that is

known to act on an A2A subtype receptor.Publication Types: Research Support, Non-U.S. Gov'tPMID: 17268086 [PubMed - indexed for MEDLINE]5: Food Chem Toxicol. 2007 May;45(5):817-26. Epub 2006 Nov 11.Related Articles, Link Protein

isolate from the herb, Phyllanthus niruri L. (Euphorbiaceae), plays

hepatoprotective role against carbon tetrachloride induced liver damage

via its antioxidant properties.Bhattacharjee R..Department of Chemistry, Bose Institute, 93/1, Acharya Prafulla Chandra Road, Kolkata 700009, West Bengal, India.Phyllanthus

niruri L. (Euphorbiaceae) (P. niruri) is a well-known hepatoprotective

herbal plant. In the present study, hepatoprotective potential of the

protein isolate of P. niruri was investigated against carbon

tetrachloride (CCl(4)) induced liver damage in vivo. Protein isolate of

P. niruri was intraperitoneally injected in mice either prior to

(preventive) or after the induction of toxicity (curative). Levels of

different liver marker enzymes in serum and different anti-oxidant

enzymes, as well as lipid peroxidation products and glutathione (GSH)

in liver homogenates were measured in normal, control (toxicity

induced) and protein isolate treated mice. Administration of CCl(4)

increased the serum glutamate pyruvate transaminase (GPT) and alkaline

phosphatase (ALP) levels of mice sera along with increased lipid

peroxidation and reduced levels of antioxidant enzymes superoxide

dismutase (SOD) and catalase (CAT) in the liver. Treatment with the

protein isolate of P. niruri significantly altered these changes to

almost normal. The protein isolate also showed protective properties as

was evidenced in histopathological studies. Results suggest that the

protein isolate of P. niruri protects liver tissues against oxidative

damage and somehow helps stimulating repair mechanism present in liver.

It could be used as an effective hepatoprotector against CCl(4) induced

liver damage.Publication Types: Research Support, Non-U.S. Gov'tPMID: 17175085 [PubMed - indexed for MEDLINE]6: Pathophysiology. 2006 May;13(2):95-102. Epub 2006 Mar 20.Related Articles, Links Herbal (Phyllanthus niruri) protein isolate protects liver from nimesulide induced oxidative stress.Chatterjee ...Department of Chemistry, Bose Institute, 93/1, Acharya Prafulla Chandra Road, Kolkata 700009, West Bengal, India.Present

study was conducted to evaluate the role of a protein fraction (PI,

protein isolate) of the herb, Phyllanthus niruri (P. niruri) against

nimesulide-induced oxidative stress in vivo using a murine model. Mice

were intraperitoneally treated with that at a dose of 5mg/kg body

weight for 7 days before and separately 1-5 days after nimesulide (at a

dose of 10mg/kg body weight for 7 days) administration to evaluate its

preventive and curative role. Levels of reduced glutathione (GSH),

antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), as

well as thiobarbituric acid reactive substances (TBARS) were measured

in the liver homogenates of all study groups. Pretreatment with

isolated P. niruri protein fraction significantly enhanced

nimesulide-induced reduced levels of antioxidant enzymes and GSH as

well as reduced the enhanced level of lipid peroxidation.

Post-treatment studies showed that the recovery after nimesulide

induced oxidative stress was more rapid if PI was administered compared

to the spontaneous recovery of liver. Histological studies also suggest

that this protein fraction could prevent as well as cure liver from

nimesulide induced oxidative stress. DPPH radical scavenging assay

showed that it could scavenge free radicals. Its antioxidant property

was compared with that of a known potent antioxidant, Vitamin E.

Besides, the effect of a non-relevant protein, BSA, was also included

in the study. Heat treatment and trypsin digestion destroyed the

biological activity of this protein fraction. In conclusion, data

obtained suggest that the P. niruri protein fraction may protect liver

from nimesulide-induced oxidative stress probably via promotion of

antioxidant defense.PMID: 16542828 [PubMed - in process]7: Biol Pharm Bull. 2006 Jan;29(1):177-9.s Vasorelaxant effects of methyl brevifolincarboxylate from the leaves of Phyllanthus niruri.Iizuka TFaculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan. iizuka@...Methyl

brevifolincarboxylate (1) isolated from the leaves of Phyllanthus

niruri L. showed a vasorelaxant effect on rat aortic rings. Compound 1

exhibited slow relaxation activity against norepinephrine (NE)-induced

contractions of rat aorta with or without endothelium. The compound did

not affect contractions induced by a high concentration (60 mM) of K+,

whereas it inhibited NE-induced vasocontraction in the presence of

nicardipine. These results suggest that the inhibition of NE-induced

vasocontraction by compound 1 is in part attributable to a decrease in

[Ca2+]i through receptor-operated Ca2+ channels.Publication Types: In Vitro Research Support, Non-U.S. Gov't PMID: 16394535 [PubMed - indexed for MEDLINE]8: J Nat Prod. 2005 Apr;68(4):537-9. Anti-babesial and anti-plasmodial compounds from Phyllanthus niruri.Subeki S..Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Sapporo 060-8589, Japan.Bioassay-guided

fractionation of boiled aqueous extracts from the whole plant of

Phyllanthus niruri led to the isolation of

1-O-galloyl-6-O-luteoyl-alpha-d-glucose (1), with IC(50) values of 4.7

microg/mL against Babesia gibsoni and 1.4 microg/mL against Plasmodium

falciparum in vitro. The known compounds beta-glucogallin (2),

quercetin 3-O-beta-d-glucopyranosyl-(2-->1)-O-beta-d-xylopyranoside

(3), beta-sitosterol, and gallic acid were also isolated. Structures of

these compounds were elucidated on the basis of their chemical and

spectroscopic data.PMID: 15844943 [PubMed - indexed for MEDLINE]9: Indian J Med Sci. 2003 Sep;57(9):387-93.s Effects of alkaloidal extract of Phyllanthus niruri on HIV replication.Naik AD, Juvekar AR.Pharmaceutical Division, Institute of Chemical Technology, University of Mumbai, Matunga, Mumbai-400019, India.Phyllanthus

niruri has been found to exhibit marked inhibitory effect on hepatitis

B virus evident by its exhaustive utility in cases of chronic jaundice.

However, till date, research has not been focused on identification and

validation of active pharmacophores of Phyllanthus niruri responsible

for the reported inhibitory effect of its aqueous extract on anti-human

immunodeficiency virus. The present investigation examines the anti-HIV

effects of the alkaloidal extract of Phyllanthus niruri in human cell

lines. The inhibitory effect on HIV replication was monitored in terms

of inhibition of virus induced cytopathogenecity in MT-4 cells. The

alkaloidal extract of Phyllanthus niruri showed suppressing activity on

strains of HIV-1 cells cultured on MT-4 cell lines. The CC50 for the

extract was found to be 279.85 microgmL(-1) whereas the EC50 was found

to be 20.98 microgmL(-1). Interestingly the Selectivity Index (SI) was

found to be 13.34, which showed a clear selective toxicity of the

extract for the viral cells. The alkaloidal extract of Phyllanthus

niruri was thus found to exhibit sensitive inhibitory response on

cytopathic effects induced by both the strains of human

immunodeficiency virus on human MT-4 cells in the tested concentrations.PMID: 14515028 [PubMed - indexed for MEDLINE]10: AIDS Res Hum Retroviruses. 1992 Nov;8(11):1937-44.Related Articles, LinksHIV-1 reverse transcriptase inhibitor from Phyllanthus niruri.Ogata ...Research Institute for Molecular Genetics, Tsumura & Co., Ibaraki-Ken, Japan.An

aqueous extract of Phyllanthus niruri (Euphorbiaceae) inhibited human

immunodeficiency virus type-1 reverse transcriptase (HIV-1-RT). The

inhibitor against HIV-1-RT in this plant was purified by combination of

three column chromatographies, Sephadex LH-20, cellulose, and

reverse-phase high-performance liquid chromatography. The inhibitor was

then identified by nuclear magnetic resonance (NMR) spectra as

repandusinic acid A monosodium salt (RA) which was originally isolated

from Mallotus repandus. The 50% inhibitory doses (ID50) of RA on

HIV-1-RT and DNA polymerase alpha (from HeLa cells) were 0.05 microM

and 0.6 microM, respectively, representing approximately a 10-fold more

sensitivity of HIV-1-RT compared with DNA polymerase alpha. RA was

shown to be a competitive inhibitor with respect to the template-primer

while it was a noncompetitive inhibitor with respect to the substrate.

RA as low as 10.1 microM inhibited HIV-1-induced cytopathogenicity in

MT-4 cells. In addition, 4.5 microM of RA inhibited HIV-1-induced giant

cell formation of SUP-T1 approximately 50%. RA (2.5 microM) inhibited

up to 90% of HIV-1 specific p24 antigen production in a Clone H9 cell

system.Publication Types: Comparative Study PMID: 1283310 [PubMed - indexed for MEDLINE]11: Proc Natl Acad Sci U S A. 1987 Jan;84(1):274-8.Related Articles, Links Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies.Venkateswaran PS, Millman I, Blumberg BS.An

aqueous extract of the plant Phyllanthus niruri inhibits endogenous DNA

polymerase of hepatitis B virus and binds to the surface antigen of

hepatitis B virus in vitro. The extract also inhibits woodchuck

hepatitis virus (WHV) DNA polymerase and binds to the surface antigen

of WHV in vitro. The extract, nontoxic to mice, was tested for

antiviral activity in woodchucks (Marmota monax). In a trial using six

long-term WHV-carrier woodchucks, five treated animals showed a faster

decrease in woodchuck hepatitis virus surface antigen titer compared to

one untreated control. In animals recently infected with WHV, the

extract was effective when administered i.p. in three out of four

animals in reducing and within 3-6 weeks eliminating both the surface

antigen titer and DNA polymerase activity in serum. The treatment was

discontinued after 10 weeks, and the treated animals have remained free

of detectable markers of WHV for more than 45 weeks. In contrast, three

untreated controls remained positive for both markers for WHV. One of

the controls died after 8 weeks; the other two controls have remained

positive for WHV markers for more than 45 weeks. In a third trial with

long-term carriers, test animals treated subcutaneously with the

extract for 12 weeks did not respond; but on switching the mode of

administration to i.p., two out of the five animals showed a

significant decrease in woodchuck hepatitis virus surface antigen titer

compared to controls.Publication Types: Research Support, Non-U.S. Gov't PMID: 3467354 [PubMed - indexed for MEDLINE]>> > > Internal Virus Database is out-of-date.> Checked by AVG Free Edition. > Version: 7.5.484 / Virus Database: 269.12.0/957 - Release Date: 8/16/2007 1:46 PM>

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