Guest guest Posted June 24, 2007 Report Share Posted June 24, 2007 e, DMSA is not metabolized, but it does participate in thiol disulfide exchange. That is kind of a big " square dance " of molecules with -SH groups exchanging partners with other molecules that have an -SH group. That sulfur (the " S " part) is really attractive to another sulfur,because the same negative charges from sulfur that make something capable of being a chelating agent, also makes it a participant in attracting another sulfur molecule and participating in thiol disulfide exchange. This process, and how it relates to proteins is illustrated here: http://www.biomedcentral.com/content/figures/1471-2105-6-19-1.jpg and here: http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/AAgif/18411m.gif http://en.wikipedia.org/wiki/Thiol http://en.wikipedia.org/wiki/Disulfide_bond Fortunately, a well-designed study looked at what came out in urine after giving someone DMSA, and no, they didn't find the DMSA all coming out bound to mercury and other heavy metals, but what they did find consistently was that it was bound to cysteine. In fact, most of the time both of its thiol or sulfur groups were bound to cysteine. Where did it get the cysteine? My guess, based on knowledge of how proteins are broken down in cells, is that this exchange very well may have taken place in the lysosome of cells. I'm sure I had a LONG explanation of this on sulfurstories explaining why I reached that conclusion many years ago based on the experimental data I could find described. Is this a bad process to be going on? It kind of depends. Almost everyone with autism seems to be low in cysteine and cystine in blood plasma, and we still don't know why, so you wouldn't want to get even lower in sulfur, especially if you are glutathione deficient as well. One thing that has haunted me is that I think the low cysteine may mean some of the process of recycling cysteine may be failing inside the cell. Why? Because breaking these proteins apart takes a thiol as you may have noticed in the illustrations I sent you to. The thiol is needed to break apart the disulfide bonds that are holding proteins together undigested in the lysosome. That attack stretches out the chain so enzymes that act on chains of amino acids can end up allowing all the amino acids in that protein to be broken up and reutilized. The studies I did years ago gave me the impression that FAR, FAR more of the amino acids we use to make new proteins come from this recycling process compared to coming from the food we eat. That's why we don't need huge amounts of protein to survive because we keep recycling the proteins that are in our cells with the help of this thiol disulfide exchange. If DMSA functions as a kind of " fake cysteine " for this process (wherever it occurs), then the DMSA may actually help the cell recycle the cysteine it hasn't been able to recycle from proteins because of sulfur deficiency. The nice thing there is that since DMSA cannot be metabolized, then someone with an excess drain of sulfur towards taurine (which can happen when the body is stressed by detoxification demands), may be rescued from this excess catabolism (throwing the sulfur away through excretion), by this use of DMSA. It may be that DMSA exchanges partners hundreds of times before getting to the urine. Nobody seems to have thought of the experimental procedure that could reveal THAT part or " count " of this exchange. Actually there is a lot about sulfur trafficking that I spent years and years trying to find, but there is so much that hasn't been studied the way it should have been. Anyway, I've thought for a long time that the benefit of DMSA may come more from this role as a " fake cysteine " compared to its role of grabbing up heavy metals. If you do the math to figure out DMSA's likelihood of finding a toxic metal versus its chances of running into a disulfide bond with which it could interchange, it is not hard to understand why the results of the study below came out the way they did. Some of the DAN! doctors have felt that they could not tell that the clinical improvements related very well with the amount of heavy metals excreted. In other words, they didn't see greater clinical improvement when more metals came out and less clinical improvement when a smaller amount of metals came out. Even so, they were pleased with the clinical improvements using the chelating agent, regardless. If such observations about clinical improvements are really solid, then it is reasonable to expect the efficacy of DMSA could come from a different contribution to chemistry or from a combination of different contributions of this non-metabolized molecule to cellular and systemic sulfur chemistry and metal-coordinating chemistry. I've put the study below that has furnished us the best data on this binding of DMSA to cysteine. Its author, Vas Aposhian, has been in our thinktank, and is a much-respected authority about chelation and the molecules that are used as chelators. Most likely the vast majority of that cysteine before its encounter with DMSA had been bound to some other thiol before this encounter took place, whether the encounter was with something that was a siamese twin made up of one type of molecule (like cysteine or GSSG) or whether it was a mixed disulfide. For more explanations of sulfur-related terminology, please see old posts on the yahoogroup, sulfurstories. The volume of new posts on that list has gone WAY down, probably because it has been a very long time since the basics of the sulfur chemistry (as opposed to methylation) have been presented as something important for parents to know at DAN! conferences. Even so, the data from ten years ago on the sulfur problems in autism still stand, and the way the biology is working or not working in this area is likely still the same although we may have learned a few more tools to change things since then. Sulfurstories was set up as a place for people (not just with autism) to share their stories of how they had good or bad results from taking sulfur supplements. It may be that Dr. Yasko's campaign of the last couple of years telling people with autism and with CBS polymorphisms common in the general population to forego basically any supplement that has sulfur in it (regardless of where it fits on the sulfur pathway) has discouraged a lot of new parents from even trying to use sulfur supplements. I would absolutely welcome to sulfurstories any discussion of the benefits or problems that anyone had following whatever advice regarding the sulfur chemistry. The way we learn and the way we find out what science remains to be done is by LOTS of observations of how people do with various approaches and by matching that experience with what is known about the basic science. I hope that helps! Toxicology. 1995 Mar 31;97(1-3):23-38.<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & DbFrom=pubm\ ed & Cmd=Link & LinkName=pubmed_pubmed & LinkReadableName=Related%20Articles & IdsFromRe\ sult=7716789 & ordinalpos=3 & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel\ ..Pubmed_RVAbstract>Related Articles, Links Mobilization of heavy metals by newer, therapeutically useful chelating agents. <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Aposhian%\ 20HV%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\ d_RVAbstract>Aposhian HV, <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Maiorino%\ 20RM%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\ d_RVAbstract>Maiorino RM, <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22-\ %20D%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPane\ l.Pubmed_RVAbstract>- D, <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Zuniga-Ch\ arles%20M%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.\ Pubmed_RVAbstract>Zuniga- M, <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Xu%20Z%22\ %5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbs\ tract>Xu Z, <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Hurlbut%2\ 0KM%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed\ _RVAbstract>Hurlbut KM, <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Junco-Mun\ oz%20P%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pub\ med_RVAbstract>Junco-Munoz P, <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Dart%20RC\ %22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RV\ Abstract>Dart RC, <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Aposhian%\ 20MM%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\ d_RVAbstract>Aposhian MM. Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721, USA. Four chelating agents that have been used most commonly for the treatment of humans intoxicated with lead, mercury, arsenic or other heavy metals and metalloids are reviewed as to their advantages, disadvantages, metabolism and specificity. Of these, CaNa2EDTA and dimercaprol (British anti-lewisite, BAL) are becoming outmoded and can be expected to be replaced by meso-2,3-dimercaptosuccinic acid (DMSA, succimer) for treatment of lead intoxication and by the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS, Dimaval) for treating lead, mercury or arsenic intoxication. Meso-2,3-DMSA and DMPS are biotransformed differently in humans. More than 90% of the DMSA excreted in the urine is found in the form of a mixed disulfide in which each of the sulfur atoms of DMSA is in disulfide linkage with an L-cysteine molecule. After DMPS administration, however, acyclic and cyclic disulfides of DMPS are found in the urine. The Dimaval-mercury challenge test holds great promise as a diagnostic test for mercury exposure, especially for low level mercurialism. Urinary mercury after Dimaval challenge may be a better biomarker of low level mercurialism than unchallenged urinary mercury excretion. Publication Types: * Research Support, U.S. Gov't, P.H.S. * Review PMID: 7716789 [PubMed - indexed for MEDLINE] At 09:08 PM 6/24/2007, you wrote: >I know this is an old post, but I am wondering if anyone has >information regarding DMSA being contraindicated for those with low >cysteine - I have read that it depletes cysteine, which my son is very >low in. > >He is mercury toxic per the porphyrins test. I have been using EDTA >suppositories and plan to add wither DMPS or DMSA as well. > >Thanks, >e > > > > > > > I just received my son's urinary porphyrin results > > > and I'm > > > devastated. > > > > > > Uro 10 > > > Hepta 4.8 > > > Hexa 1.0 > > > Penta 14.1 > > > Preco 41 > > > Copro 515 > > > Remarkable mercury toxicity > > > > > > Neopterin 1,004 > > > Biopterin 182 > > > Biopt / Neopt ratio 0.16 > > > Really increased cellular immunity activation > > > > > > Urinary creatinin 1,206 > > > > > > My son, , is 4 (almost 5) years old. We've > > > been doing biomed > > > for over 2 years (diet, probiotics, antifungals, > > > enzymes, MB12, tons > > > of supplements.) We've done TD-DMPS, 3 IVs, oral > > > EDTA and EDTA > > > suppositories. Still doing the EDTA suppositories. > > > is an > > > under-methylator and we've never got great pulls on > > > anything. He > > > regressed on TD-DMPS. I think it's because he has > > > the CBS up > > > regulation. After his regression I switched to > > > Yasko and have been > > > doing that for the past few months. Started BH4 in > > > December and > > > has been doing very well on Yasko's protocol. > > > Any advice on > > > how to proceed would be appreciated. Do I stick > > > with Yasko in light > > > of these results with such high mercury and such > > > high neopterin? > > > What exactly would you do if your child received > > > these test results? > > > Any advice/suggestions would be appreciated. > > > > > > Thank you, > > > Sheri > > > > > > > > > > > > > -- No virus found in this outgoing message. Checked by AVG Free Edition. Version: 7.5.472 / Virus Database: 269.9.6/865 - Release Date: 6/24/2007 8:33 AM Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 25, 2007 Report Share Posted June 25, 2007 Thank you, for the details and the references. I have been curious about such studies and if indeed DMSA bound to metals has been detected in samples following a round of chelating. I will join the sulphurstories and hope to get more answeres from the archives and posts. I have a couple of questions- 1. When you say that some have found no correlation between amount of metals excreted after a chelation procedure and improvements, have they looked into synergistic effects of all metal toxins and total body burden in the body? For example if Hg is coming out but thallium is still in, would one see improvements? Anyway, I have taught myself to look at improvements and not wholly at metal levels coming out. 2. Can you give any references to transport mechanisms: say, after a chelating molecule attaches itself to a metal toxin, how does the surrounding concentration or gradients of minerals, antioxidants and other nutrients affect the efficacy of removal from body as opposed to redeposition on other tissues. 3. How does ALA work as opposed to DMSA or DMPS (very few DAN doctors use ALA). BTW, if I understand correctly, Dr. Amy asks to use low sulphur until the CBS upregulation is plugged. Once kept under control she believes that sulphur supplementation can help if given in a controlled way. We don't have CBS upregulation but I still keep an eye on total sulphur. Thank you, Smita > > e, > > DMSA is not metabolized, but it does participate in thiol disulfide > exchange. That is kind of a big " square dance " of molecules with -SH > groups exchanging partners with other molecules that have an -SH > group. That sulfur (the " S " part) is really attractive to another > sulfur,because the same negative charges from sulfur that make something > capable of being a chelating agent, also makes it a participant in > attracting another sulfur molecule and participating in thiol disulfide > exchange. This process, and how it relates to proteins is illustrated > here: > > http://www.biomedcentral.com/content/figures/1471-2105-6-19-1.jpg > > and here: > > http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/AAgif/18411m.gif > > http://en.wikipedia.org/wiki/Thiol > > http://en.wikipedia.org/wiki/Disulfide_bond > > Fortunately, a well-designed study looked at what came out in urine after > giving someone DMSA, and no, they didn't find the DMSA all coming out > bound > to mercury and other heavy metals, but what they did find consistently was > > that it was bound to cysteine. In fact, most of the time both of its thiol > > or sulfur groups were bound to cysteine. > > Where did it get the cysteine? My guess, based on knowledge of how > proteins are broken down in cells, is that this exchange very well may > have > taken place in the lysosome of cells. I'm sure I had a LONG explanation of > > this on sulfurstories explaining why I reached that conclusion many years > ago based on the experimental data I could find described. > > Is this a bad process to be going on? It kind of depends. Almost everyone > with autism seems to be low in cysteine and cystine in blood plasma, and > we > still don't know why, so you wouldn't want to get even lower in sulfur, > especially if you are glutathione deficient as well. One thing that has > haunted me is that I think the low cysteine may mean some of the process > of > recycling cysteine may be failing inside the cell. Why? Because breaking > these proteins apart takes a thiol as you may have noticed in the > illustrations I sent you to. The thiol is needed to break apart the > disulfide bonds that are holding proteins together undigested in the > lysosome. That attack stretches out the chain so enzymes that act on > chains of amino acids can end up allowing all the amino acids in that > protein to be broken up and reutilized. The studies I did years ago gave > me the impression that FAR, FAR more of the amino acids we use to make new > > proteins come from this recycling process compared to coming from the food > > we eat. That's why we don't need huge amounts of protein to survive > because we keep recycling the proteins that are in our cells with the help > > of this thiol disulfide exchange. > > If DMSA functions as a kind of " fake cysteine " for this process (wherever > it occurs), then the DMSA may actually help the cell recycle the cysteine > it hasn't been able to recycle from proteins because of sulfur > deficiency. The nice thing there is that since DMSA cannot be metabolized, > > then someone with an excess drain of sulfur towards taurine (which can > happen when the body is stressed by detoxification demands), may be > rescued > from this excess catabolism (throwing the sulfur away through excretion), > by this use of DMSA. It may be that DMSA exchanges partners hundreds of > times before getting to the urine. Nobody seems to have thought of the > experimental procedure that could reveal THAT part or " count " of this > exchange. Actually there is a lot about sulfur trafficking that I spent > years and years trying to find, but there is so much that hasn't been > studied the way it should have been. Anyway, I've thought for a long time > that the benefit of DMSA may come more from this role as a " fake cysteine " > > compared to its role of grabbing up heavy metals. > > If you do the math to figure out DMSA's likelihood of finding a toxic > metal > versus its chances of running into a disulfide bond with which it could > interchange, it is not hard to understand why the results of the study > below came out the way they did. > > Some of the DAN! doctors have felt that they could not tell that the > clinical improvements related very well with the amount of heavy metals > excreted. In other words, they didn't see greater clinical improvement > when > more metals came out and less clinical improvement when a smaller amount > of > metals came out. Even so, they were pleased with the clinical improvements > > using the chelating agent, regardless. > > If such observations about clinical improvements are really solid, then > it is reasonable to expect the efficacy of DMSA could come from a > different contribution to chemistry or from a combination of different > contributions of this non-metabolized molecule to cellular and systemic > sulfur chemistry and metal-coordinating chemistry. > > I've put the study below that has furnished us the best data on this > binding of DMSA to cysteine. Its author, Vas Aposhian, has been in our > thinktank, and is a much-respected authority about chelation and the > molecules that are used as chelators. > > Most likely the vast majority of that cysteine before its encounter with > DMSA had been bound to some other thiol before this encounter took place, > whether the encounter was with something that was a siamese twin made up > of > one type of molecule (like cysteine or GSSG) or whether it was a mixed > disulfide. > > For more explanations of sulfur-related terminology, please see old posts > on the yahoogroup, sulfurstories. > > The volume of new posts on that list has gone WAY down, probably because > it > has been a very long time since the basics of the sulfur chemistry (as > opposed to methylation) have been presented as something important for > parents to know at DAN! conferences. Even so, the data from ten years ago > on the sulfur problems in autism still stand, and the way the biology is > working or not working in this area is likely still the same although we > may have learned a few more tools to change things since then. > > Sulfurstories was set up as a place for people (not just with autism) to > share their stories of how they had good or bad results from taking sulfur > > supplements. It may be that Dr. Yasko's campaign of the last couple of > years telling people with autism and with CBS polymorphisms common in the > general population to forego basically any supplement that has sulfur in > it > (regardless of where it fits on the sulfur pathway) has discouraged a lot > of new parents from even trying to use sulfur supplements. I would > absolutely welcome to sulfurstories any discussion of the benefits or > problems that anyone had following whatever advice regarding the sulfur > chemistry. The way we learn and the way we find out what science remains > to be done is by LOTS of observations of how people do with various > approaches and by matching that experience with what is known about the > basic science. > > I hope that helps! > > > > Toxicology. 1995 Mar > 31;97(1-3):23-38.< > http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & DbFrom=pubmed & Cmd=Link & LinkNa\ me=pubmed_pubmed & LinkReadableName=Related%20Articles & IdsFromResult=7716789 & ordin\ alpos=3 & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract\ >Related > > Articles, Links > > Mobilization of heavy metals by newer, therapeutically useful chelating > agents. > > < > http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Aposhian%2\ 0HV%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed\ _RVAbstract>Aposhian > > HV, > < > http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Maiorino%2\ 0RM%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed\ _RVAbstract>Maiorino > > RM, > < > http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22-R\ amirez%20D%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel\ ..Pubmed_RVAbstract>- > > D, > < > http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Zuniga-Cha\ rles%20M%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.P\ ubmed_RVAbstract>Zuniga- > > M, > < > http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Xu%20Z%22%\ 5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbst\ ract>Xu > > Z, > < > http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Hurlbut%20\ KM%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_\ RVAbstract>Hurlbut > > KM, > < > http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Junco-Muno\ z%20P%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubm\ ed_RVAbstract>Junco-Munoz > > P, > < > http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Dart%20RC%\ 22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVA\ bstract>Dart > > RC, > < > http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Aposhian%2\ 0MM%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed\ _RVAbstract>Aposhian > > MM. > > Department of Molecular and Cellular Biology, University of Arizona, > Tucson > 85721, USA. > > Four chelating agents that have been used most commonly for the treatment > of humans intoxicated with lead, mercury, arsenic or other heavy metals > and > metalloids are reviewed as to their advantages, disadvantages, metabolism > and specificity. Of these, CaNa2EDTA and dimercaprol (British > anti-lewisite, BAL) are becoming outmoded and can be expected to be > replaced by meso-2,3-dimercaptosuccinic acid (DMSA, succimer) for > treatment > of lead intoxication and by the sodium salt of > 2,3-dimercapto-1-propanesulfonic acid (DMPS, Dimaval) for treating lead, > mercury or arsenic intoxication. Meso-2,3-DMSA and DMPS are biotransformed > > differently in humans. More than 90% of the DMSA excreted in the urine is > found in the form of a mixed disulfide in which each of the sulfur atoms > of > DMSA is in disulfide linkage with an L-cysteine molecule. After DMPS > administration, however, acyclic and cyclic disulfides of DMPS are found > in > the urine. The Dimaval-mercury challenge test holds great promise as a > diagnostic test for mercury exposure, especially for low level > mercurialism. Urinary mercury after Dimaval challenge may be a better > biomarker of low level mercurialism than unchallenged urinary mercury > excretion. > > Publication Types: > * Research Support, U.S. Gov't, P.H.S. > * Review > > PMID: 7716789 [PubMed - indexed for MEDLINE] > At 09:08 PM 6/24/2007, you wrote: > > >I know this is an old post, but I am wondering if anyone has > >information regarding DMSA being contraindicated for those with low > >cysteine - I have read that it depletes cysteine, which my son is very > >low in. > > > >He is mercury toxic per the porphyrins test. I have been using EDTA > >suppositories and plan to add wither DMPS or DMSA as well. > > > >Thanks, > >e > > > > > > > > > > > I just received my son's urinary porphyrin results > > > > and I'm > > > > devastated. > > > > > > > > Uro 10 > > > > Hepta 4.8 > > > > Hexa 1.0 > > > > Penta 14.1 > > > > Preco 41 > > > > Copro 515 > > > > Remarkable mercury toxicity > > > > > > > > Neopterin 1,004 > > > > Biopterin 182 > > > > Biopt / Neopt ratio 0.16 > > > > Really increased cellular immunity activation > > > > > > > > Urinary creatinin 1,206 > > > > > > > > My son, , is 4 (almost 5) years old. We've > > > > been doing biomed > > > > for over 2 years (diet, probiotics, antifungals, > > > > enzymes, MB12, tons > > > > of supplements.) We've done TD-DMPS, 3 IVs, oral > > > > EDTA and EDTA > > > > suppositories. Still doing the EDTA suppositories. > > > > is an > > > > under-methylator and we've never got great pulls on > > > > anything. He > > > > regressed on TD-DMPS. I think it's because he has > > > > the CBS up > > > > regulation. After his regression I switched to > > > > Yasko and have been > > > > doing that for the past few months. Started BH4 in > > > > December and > > > > has been doing very well on Yasko's protocol. > > > > Any advice on > > > > how to proceed would be appreciated. Do I stick > > > > with Yasko in light > > > > of these results with such high mercury and such > > > > high neopterin? > > > > What exactly would you do if your child received > > > > these test results? > > > > Any advice/suggestions would be appreciated. > > > > > > > > Thank you, > > > > Sheri > > > > > > > > > > > > > > > > > > > > > -- > No virus found in this outgoing message. > Checked by AVG Free Edition. > Version: 7.5.472 / Virus Database: 269.9.6/865 - Release Date: 6/24/2007 > 8:33 AM > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 27, 2007 Report Share Posted June 27, 2007 Smita, I love you how you think, which is so ably demonstrated by your excellent questions! Compartmentation is a fancy word for knowing where something is and the rules of that place. When you are chelating, presumably what you are doing is moving something out of one compartment and putting it in another where you think it will do less damage and can hopefully leave the body. I wish the scientists had provided us the answer to your sorts of question, but it is hard to " freeze " the timing of the movement of these compounds in the body in a way that would help us understand the changes in compartmentation. Years ago when I started studying the metal issues as Sally and and others were first combing through the literature looking for parallels between autism and mercury toxicity, I was looking for different sorts of studies, because my training is more about the interactions of enzymes and transporters and the MOTION of things in our bodies. I was asking WHERE do the metals go and why and what are they doing once they get there. Every study which attempted to answer that question seemed to have come to the same conclusion, that within a few days of exposure almost all the mercury ends up in the lysosome of cells and it stays there, and it likes particularly kidney cells. The lysosome is where proteins are broken down and their ingredients (amino acids) are made accessible and exported to make new proteins. Something about the mercury being stuck in the lysosome suggested that the ordinary process of breaking things apart in the lysosome became compromised by this stashing away of mercury (probably bound to metallothionenin) . I spent a lot of time studying how metallothionein is usually unloaded of its cargo of cations that it picks up. I spoke about this about three AutismOne Conferences ago. Back at the beginning of the mercury theory's heyday, I read a lot about other situations when lysosomal function breaks down similarly. I later became totally immersed in thinking about the implications of one case study...the tale of a Darmouth professor who spilled a few drops of dimethylmercury on her gloved hand, and thought she hadn't been injured or exposed to excessive mercury because she didn't develop symptoms. It was 168 days before she went to the doctor because at that point she was STARTING to have neurological signs. 168 days! Clearly by that time she had already detoxed a lot of mercury, as her hair showed that in ways that already had precedent. When she came into the hospital, and when they recognized the situation, they immediately began chelating her, and the first day of chelation she put out 39 MILLIGRAMS of mercury in her urine, or 39,000 micrograms. This is a completely different scale from what we were finding in chelating children with autism. Within a few months of her hospitalization, all the while being chlelated, she eventually died. What haunted me is how many months with that level of toxicity she got by just fine before her body crashed. Obviously whatever enzyme inhibition was going on, for months, it wasn't major and she had far more exposure to mercury at the beginning of her exposure compared to the end. Also, she got WAY more mercury exposure than what kids got in vaccines. I had to think about that. This case report seemed to me to invalidate a lot of the models going around in that day which suggested that tiny amounts of these metals from the vaccines were responsible alone for the autism epidemic. (I still think the vacccines are at fault, but for different reasons, but the mercury certainly was awful, too.) Anyway, back then I kept wondering what we could learn from this lady's life and death. If mercury was THAT toxic, then what about the nature of heavy metal toxicity allowed this lady to go about her life normally for so many months after her exposure? And then, what changed after all those months went by? What caused the neurological signs that didn't show up until months later? If we were chelating children months after their exposures to thimerosal, then where we were expecting these chelating agents to go and how did we expect that they would find the metals if the metals were now pretty reliably located in the lysosome? Dr. Aposhian didn't think DMSA could get to the lysosome. If that is where all the studies say mercury ends up, how were those chelating agents finding and detoxifying it? Those are the sorts of questions I began to ask, but the literature on this subject was so limited. You can find a lot of discussion of my thoughts and the literature I found at the time on Sulfurstories. At any rate, I was so delighted to find Aposhian's study about DMSA showing it being bound to cysteine. One of the things in that day that REALLY bugged me was that it was being said that when urinary levels of mercury went down after a period of chelation that this meant that the " body burden " of mercury was finally gone, and that meant it would be safe to use agents that would cross the blood brain barrier, like presumably ALA. But I had read that the professor from Dartmouth's level of mercury coming out in urine with chelation went down to nothing at one point, and then started to go back up until it fell off again right before she died. At autopsy, far from there being no burden of mercury outside the brain after the metals stopped coming out under provocation, instead, they found huge amounts of mercury in her kidneys and all over her body.On autopsy, her brain had 3.1 ug/gram of mercury, but her liver had, 20.1 ug/gram, and her kidney cortex had 34.8 ug/gram...certainly it was NOT true in her case that the lowered levels of mercury in urine meant that the body burden was now down. But what did it mean? Anyway, Smita, since this area is interesting to you, you would probably enjoy reading old posts I wrote on mercury issues in the archives of sulfurstories (and abmd), If you look at quantitative issues, the numbers and this binding to cysteine do suggest that a different process could be going on with these chelating agents, and perhaps it is the other mechanisms at work that are producing so much benefit. Maybe if we are chelating children now who didn't have much exposure to thimerosal and they are getting better, then it is confirming that we need to look harder at mechanisms. Mercury and chelating agents like to bind thiols, so they " act " where you see a lot of thiol disulfide exchange. The kidney is where so much of that exchange takes place, and this probably explains why the kidney gets the highest burden of mercury in systemic mercury exposures. I have a slide I show where kidney doctors scanned a person with kidney disease using labelled DMSA, and quickly it went from being pretty evenly distributed in the body to being intensely concentrated in the kidney and bladder. That must be because there is something going on in the kidney involving thiol disulfide exchange that makes it stay there. So, it matters that we cannot seem to answer the " whys " of what people have noticed about the order that certain metals get excreted under the influence of chelating agents because we don't even know where the chelating agent is finding what it is finding (even if that is cysteine!), and we don't know if it just liberates the metal, or if it provides an escort all the way to the urine. I wish those questions had been asked! Science really involves a lot of dialogue and a lot of uncertainty. Sometimes reearch in a field gets directed by those with a certain mindset who never get around to asking " How do we know that we have the mechanism right? " Smita, what does Dr. Yasko mean by saying something has the mechanism plugged? Can you elaborate? I thought she was talking about things driven by genetics! Something plugging something certainly sounds " environmental " , especially if you can change this with supplements!. Are her models changing now? Toxicol Appl Pharmacol. 1990 Apr;103(2):303-23.<http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & DbFrom=pub\ med & Cmd=Link & LinkName=pubmed_pubmed & LinkReadableName=Related%20Articles & IdsFromR\ esult=2330591 & ordinalpos=1 & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPane\ l.Pubmed_RVAbstract>Related Articles, Links Localization of mercury in CNS of the rat. II. Intraperitoneal injection of methylmercuric chloride (CH3HgCl) and mercuric chloride (HgCl2). <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22M%C3%B8ll\ er-Madsen%20B%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPa\ nel.Pubmed_RVAbstract>Møller-Madsen B. Department of Neurobiology, University of Aarhus, Denmark. The autometallographic method has been used to determine the precise localization of mercury in the brain and spinal cord of adult Wistar rats which had been treated with repeated ip injections of methylmercuric chloride (CH3HgCl; 0.2 to 10.0 mg) or mercuric chloride (HgCl2; 0.2 to 10.0 mg). The distribution of mercury was uneven following administration of HgCl2, while it was fairly homogeneous following CH3HgCl. With both compounds, however, heavy deposits of mercury were present in the motor nuclei of rhombencephalon. In contrast, cerebellar Purkinje cells, Golgi cells, and Golgi epithelial cells only contained mercury in sections from rats exposed to CH3HgCl. In cerebral sections from rats exposed to CH3HgCl, staining intensity in cortical cells varied among the layers, being greatest in laminae III, V, and VI. On the other hand, sections from rats exposed to HgCl2 showed only staining in scattered cells of lamina VI. Following administration of either compound, mercury was detected in the gray matter of the spinal cord mercury. Particularly large deposits were present in the anterior horn motoneurons. At the cellular level, the heaviest staining intensity was seen in neurons, although the cytoplasm of glia and ependymal cells also showed significant deposits in sections from rats exposed to CH3HgCl. In HgCl2-treated rats, the largest accumulations of mercury were seen in the neurons. The ependymal cells were stained to a lesser extent, while glia were devoid of mercury. Ultrastructurally, mercury deposits were located exclusively in lysosomes. The present results demonstrate that the pattern of mercury distribution and its staining intensity in individual cells in the rat CNS are dependent upon the chemical structure of the compound and the duration of its administration. Publication Types: * Comparative Study * Research Support, Non-U.S. Gov't PMID: 2330591 [PubMed - indexed for MEDLINE] At 09:50 PM 6/25/2007, you wrote: >Thank you, for the details and the references. I have been curious >about such studies and if indeed DMSA bound to metals has been detected in >samples following a round of chelating. > >I will join the sulphurstories and hope to get more answeres from the >archives and posts. > >I have a couple of questions- >1. When you say that some have found no correlation between amount of metals >excreted after a chelation procedure and improvements, have they looked >into synergistic effects of all metal toxins and total body burden in the >body? For example if Hg is coming out but thallium is still in, would one >see improvements? Anyway, I have taught myself to look at improvements and >not wholly at metal levels coming out. >2. Can you give any references to transport mechanisms: say, after a >chelating molecule attaches itself to a metal toxin, how does the >surrounding concentration or gradients of minerals, antioxidants and other >nutrients affect the efficacy of removal from body as opposed to >redeposition on other tissues. >3. How does ALA work as opposed to DMSA or DMPS (very few DAN doctors use >ALA). > >BTW, if I understand correctly, Dr. Amy asks to use low sulphur until the >CBS upregulation is plugged. Once kept under control she believes that >sulphur supplementation can help if given in a controlled way. We don't have >CBS upregulation but I still keep an eye on total sulphur. > >Thank you, >Smita > > > > > > e, > > > > DMSA is not metabolized, but it does participate in thiol disulfide > > exchange. That is kind of a big " square dance " of molecules with -SH > > groups exchanging partners with other molecules that have an -SH > > group. That sulfur (the " S " part) is really attractive to another > > sulfur,because the same negative charges from sulfur that make something > > capable of being a chelating agent, also makes it a participant in > > attracting another sulfur molecule and participating in thiol disulfide > > exchange. This process, and how it relates to proteins is illustrated > > here: > > > > > <http://www.biomedcentral.com/content/figures/1471-2105-6-19-1.jpg>http://www.bi\ omedcentral.com/content/figures/1471-2105-6-19-1.jpg > > > > and here: > > > > > <http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/AAgif/18411m.gif>htt\ p://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/AAgif/18411m.gif > > > > http://en.wikipedia.org/wiki/Thiol > > > > > <http://en.wikipedia.org/wiki/Disulfide_bond>http://en.wikipedia.org/wiki/Disulf\ ide_bond > > > > Fortunately, a well-designed study looked at what came out in urine after > > giving someone DMSA, and no, they didn't find the DMSA all coming out > > bound > > to mercury and other heavy metals, but what they did find consistently was > > > > that it was bound to cysteine. In fact, most of the time both of its thiol > > > > or sulfur groups were bound to cysteine. > > > > Where did it get the cysteine? My guess, based on knowledge of how > > proteins are broken down in cells, is that this exchange very well may > > have > > taken place in the lysosome of cells. I'm sure I had a LONG explanation of > > > > this on sulfurstories explaining why I reached that conclusion many years > > ago based on the experimental data I could find described. > > > > Is this a bad process to be going on? It kind of depends. Almost everyone > > with autism seems to be low in cysteine and cystine in blood plasma, and > > we > > still don't know why, so you wouldn't want to get even lower in sulfur, > > especially if you are glutathione deficient as well. One thing that has > > haunted me is that I think the low cysteine may mean some of the process > > of > > recycling cysteine may be failing inside the cell. Why? Because breaking > > these proteins apart takes a thiol as you may have noticed in the > > illustrations I sent you to. The thiol is needed to break apart the > > disulfide bonds that are holding proteins together undigested in the > > lysosome. That attack stretches out the chain so enzymes that act on > > chains of amino acids can end up allowing all the amino acids in that > > protein to be broken up and reutilized. The studies I did years ago gave > > me the impression that FAR, FAR more of the amino acids we use to make new > > > > proteins come from this recycling process compared to coming from the food > > > > we eat. That's why we don't need huge amounts of protein to survive > > because we keep recycling the proteins that are in our cells with the help > > > > of this thiol disulfide exchange. > > > > If DMSA functions as a kind of " fake cysteine " for this process (wherever > > it occurs), then the DMSA may actually help the cell recycle the cysteine > > it hasn't been able to recycle from proteins because of sulfur > > deficiency. The nice thing there is that since DMSA cannot be metabolized, > > > > then someone with an excess drain of sulfur towards taurine (which can > > happen when the body is stressed by detoxification demands), may be > > rescued > > from this excess catabolism (throwing the sulfur away through excretion), > > by this use of DMSA. It may be that DMSA exchanges partners hundreds of > > times before getting to the urine. Nobody seems to have thought of the > > experimental procedure that could reveal THAT part or " count " of this > > exchange. Actually there is a lot about sulfur trafficking that I spent > > years and years trying to find, but there is so much that hasn't been > > studied the way it should have been. Anyway, I've thought for a long time > > that the benefit of DMSA may come more from this role as a " fake cysteine " > > > > compared to its role of grabbing up heavy metals. > > > > If you do the math to figure out DMSA's likelihood of finding a toxic > > metal > > versus its chances of running into a disulfide bond with which it could > > interchange, it is not hard to understand why the results of the study > > below came out the way they did. > > > > Some of the DAN! doctors have felt that they could not tell that the > > clinical improvements related very well with the amount of heavy metals > > excreted. In other words, they didn't see greater clinical improvement > > when > > more metals came out and less clinical improvement when a smaller amount > > of > > metals came out. Even so, they were pleased with the clinical improvements > > > > using the chelating agent, regardless. > > > > If such observations about clinical improvements are really solid, then > > it is reasonable to expect the efficacy of DMSA could come from a > > different contribution to chemistry or from a combination of different > > contributions of this non-metabolized molecule to cellular and systemic > > sulfur chemistry and metal-coordinating chemistry. > > > > I've put the study below that has furnished us the best data on this > > binding of DMSA to cysteine. Its author, Vas Aposhian, has been in our > > thinktank, and is a much-respected authority about chelation and the > > molecules that are used as chelators. > > > > Most likely the vast majority of that cysteine before its encounter with > > DMSA had been bound to some other thiol before this encounter took place, > > whether the encounter was with something that was a siamese twin made up > > of > > one type of molecule (like cysteine or GSSG) or whether it was a mixed > > disulfide. > > > > For more explanations of sulfur-related terminology, please see old posts > > on the yahoogroup, sulfurstories. > > > > The volume of new posts on that list has gone WAY down, probably because > > it > > has been a very long time since the basics of the sulfur chemistry (as > > opposed to methylation) have been presented as something important for > > parents to know at DAN! conferences. Even so, the data from ten years ago > > on the sulfur problems in autism still stand, and the way the biology is > > working or not working in this area is likely still the same although we > > may have learned a few more tools to change things since then. > > > > Sulfurstories was set up as a place for people (not just with autism) to > > share their stories of how they had good or bad results from taking sulfur > > > > supplements. It may be that Dr. Yasko's campaign of the last couple of > > years telling people with autism and with CBS polymorphisms common in the > > general population to forego basically any supplement that has sulfur in > > it > > (regardless of where it fits on the sulfur pathway) has discouraged a lot > > of new parents from even trying to use sulfur supplements. I would > > absolutely welcome to sulfurstories any discussion of the benefits or > > problems that anyone had following whatever advice regarding the sulfur > > chemistry. The way we learn and the way we find out what science remains > > to be done is by LOTS of observations of how people do with various > > approaches and by matching that experience with what is known about the > > basic science. > > > > I hope that helps! > > > > > > > > Toxicology. 1995 Mar > > 31;97(1-3):23-38.< > > > <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & DbFrom=pubmed & Cmd=Link & LinkN\ ame=pubmed_pubmed & LinkReadableName=Related%20Articles & IdsFromResult=7716789 & ordi\ nalpos=3 & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstrac\ t>http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & DbFrom=pubmed & Cmd=Link & Link\ Name=pubmed_pubmed & LinkReadableName=Related%20Articles & IdsFromResult=7716789 & ord\ inalpos=3 & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstra\ ct>Related > > > > Articles, Links > > > > Mobilization of heavy metals by newer, therapeutically useful chelating > > agents. > > > > < > > > <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Aposhian%\ 20HV%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\ d_RVAbstract>http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=\ %22Aposhian%20HV%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_Result\ sPanel.Pubmed_RVAbstract>Aposhian > > > > HV, > > < > > > <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Maiorino%\ 20RM%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\ d_RVAbstract>http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=\ %22Maiorino%20RM%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_Result\ sPanel.Pubmed_RVAbstract>Maiorino > > > > RM, > > < > > > <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22-\ %20D%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPane\ l.Pubmed_RVAbstract>http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Searc\ h & Term=%22-%20D%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed\ ..Pubmed_ResultsPanel.Pubmed_RVAbstract>- > > > > D, > > < > > > <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Zuniga-Ch\ arles%20M%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.\ Pubmed_RVAbstract>http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & \ Term=%22Zuniga-%20M%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pub\ med_ResultsPanel.Pubmed_RVAbstract>Zuniga- > > > > M, > > < > > > <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Xu%20Z%22\ %5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbs\ tract>http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Xu%2\ 0Z%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_\ RVAbstract>Xu > > > > Z, > > < > > > <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Hurlbut%2\ 0KM%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed\ _RVAbstract>http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%\ 22Hurlbut%20KM%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP\ anel.Pubmed_RVAbstract>Hurlbut > > > > KM, > > < > > > <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Junco-Mun\ oz%20P%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pub\ med_RVAbstract>http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Ter\ m=%22Junco-Munoz%20P%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_Re\ sultsPanel.Pubmed_RVAbstract>Junco-Munoz > > > > P, > > < > > > <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Dart%20RC\ %22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RV\ Abstract>http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22D\ art%20RC%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.P\ ubmed_RVAbstract>Dart > > > > RC, > > < > > > <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=%22Aposhian%\ 20MM%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubme\ d_RVAbstract>http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed & Cmd=Search & Term=\ %22Aposhian%20MM%22%5BAuthor%5D & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_Result\ sPanel.Pubmed_RVAbstract>Aposhian > > > > MM. > > > > Department of Molecular and Cellular Biology, University of Arizona, > > Tucson > > 85721, USA. > > > > Four chelating agents that have been used most commonly for the treatment > > of humans intoxicated with lead, mercury, arsenic or other heavy metals > > and > > metalloids are reviewed as to their advantages, disadvantages, metabolism > > and specificity. Of these, CaNa2EDTA and dimercaprol (British > > anti-lewisite, BAL) are becoming outmoded and can be expected to be > > replaced by meso-2,3-dimercaptosuccinic acid (DMSA, succimer) for > > treatment > > of lead intoxication and by the sodium salt of > > 2,3-dimercapto-1-propanesulfonic acid (DMPS, Dimaval) for treating lead, > > mercury or arsenic intoxication. Meso-2,3-DMSA and DMPS are biotransformed > > > > differently in humans. More than 90% of the DMSA excreted in the urine is > > found in the form of a mixed disulfide in which each of the sulfur atoms > > of > > DMSA is in disulfide linkage with an L-cysteine molecule. After DMPS > > administration, however, acyclic and cyclic disulfides of DMPS are found > > in > > the urine. The Dimaval-mercury challenge test holds great promise as a > > diagnostic test for mercury exposure, especially for low level > > mercurialism. Urinary mercury after Dimaval challenge may be a better > > biomarker of low level mercurialism than unchallenged urinary mercury > > excretion. > > > > Publication Types: > > * Research Support, U.S. Gov't, P.H.S. > > * Review > > > > PMID: 7716789 [PubMed - indexed for MEDLINE] > > At 09:08 PM 6/24/2007, you wrote: > > > > >I know this is an old post, but I am wondering if anyone has > > >information regarding DMSA being contraindicated for those with low > > >cysteine - I have read that it depletes cysteine, which my son is very > > >low in. > > > > > >He is mercury toxic per the porphyrins test. I have been using EDTA > > >suppositories and plan to add wither DMPS or DMSA as well. > > > > > >Thanks, > > >e > > > > > > > > > > > > > > > I just received my son's urinary porphyrin results > > > > > and I'm > > > > > devastated. > > > > > > > > > > Uro 10 > > > > > Hepta 4.8 > > > > > Hexa 1.0 > > > > > Penta 14.1 > > > > > Preco 41 > > > > > Copro 515 > > > > > Remarkable mercury toxicity > > > > > > > > > > Neopterin 1,004 > > > > > Biopterin 182 > > > > > Biopt / Neopt ratio 0.16 > > > > > Really increased cellular immunity activation > > > > > > > > > > Urinary creatinin 1,206 > > > > > > > > > > My son, , is 4 (almost 5) years old. We've > > > > > been doing biomed > > > > > for over 2 years (diet, probiotics, antifungals, > > > > > enzymes, MB12, tons > > > > > of supplements.) We've done TD-DMPS, 3 IVs, oral > > > > > EDTA and EDTA > > > > > suppositories. Still doing the EDTA suppositories. > > > > > is an > > > > > under-methylator and we've never got great pulls on > > > > > anything. He > > > > > regressed on TD-DMPS. I think it's because he has > > > > > the CBS up > > > > > regulation. After his regression I switched to > > > > > Yasko and have been > > > > > doing that for the past few months. Started BH4 in > > > > > December and > > > > > has been doing very well on Yasko's protocol. > > > > > Any advice on > > > > > how to proceed would be appreciated. Do I stick > > > > > with Yasko in light > > > > > of these results with such high mercury and such > > > > > high neopterin? > > > > > What exactly would you do if your child received > > > > > these test results? > > > > > Any advice/suggestions would be appreciated. > > > > > > > > > > Thank you, > > > > > Sheri > > > > > > > > > > > > > > > > > > > > > > > > > > > > > -- > > No virus found in this outgoing message. > > Checked by AVG Free Edition. > > Version: 7.5.472 / Virus Database: 269.9.6/865 - Release Date: 6/24/2007 > > 8:33 AM > > > > > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 30, 2007 Report Share Posted June 30, 2007 , thank you so much for your incredible reply - you are always an amazing source of information. I hope you can ferret out more information about Yasko and CBS and how it relates to your sulfur studies. If anyone can figure out how to bridge the gap of information between DAN and Yasko it's you. I will spend a lot of time working through all the excellent information you have shared! e > > e, > > DMSA is not metabolized, but it does participate in thiol disulfide > exchange. That is kind of a big " square dance " of molecules with -SH > groups exchanging partners with other molecules that have an -SH > group. That sulfur (the " S " part) is really attractive to another > sulfur,because the same negative charges from sulfur that make something > capable of being a chelating agent, also makes it a participant in > attracting another sulfur molecule and participating in thiol disulfide > exchange. This process, and how it relates to proteins is illustrated here: > > http://www.biomedcentral.com/content/figures/1471-2105-6-19-1.jpg > > and here: > http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/AAgif/18411m.gif > > http://en.wikipedia.org/wiki/Thiol > > http://en.wikipedia.org/wiki/Disulfide_bond > > Fortunately, a well-designed study looked at what came out in urine after > giving someone DMSA, and no, they didn't find the DMSA all coming out bound > to mercury and other heavy metals, but what they did find consistently was > that it was bound to cysteine. In fact, most of the time both of its thiol > or sulfur groups were bound to cysteine. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 30, 2007 Report Share Posted June 30, 2007 Thank you, for your reply. It was just what I was looking for and > gives me directions for my search. I appreciate your time and insight. > The research and your findings are very intriguing. I have a child involved so the emotions are harder to manage. Atleast I have a better idea of how to start understanding chelation. Aside from the input of chelators and output (hopefully) of metals, there is so much in the middle that dictates the success of this process. I have parallel thoughts: 1. Dr. Amy Holmes chart that says chelation done on the younger side of a child is more successful (metals can get deeper into tissues if we wait too long). 2. But natural detox, say giving the body ability to dump on its own is slow but can very effective for those it works (say, Valtrex like in S.Kurtz's son Ethan and/or Dr. Amy Yasko's protocol and few other rare protocols). If I hypothesize that recovery or improvement correlates with *what* metals are excreted and *what* corresponding metabolic processes are restored that make sense for the person in question rather than *how much* metals come out, I lean towards natural detox because then we let the body figure out what it needs to do for the viscous cycles to turn into virtuous ones. But then, I worry much about point (1). I wonder if anyone has done kidney stress tests along with aggresive chelation, say, with IV's. Re. Dr. Amy Yasko's protocol- I view it as continuous work in progress. There is much art and science and she is the main artscientist. I believe the protocol changes ever so slightly as newer findings emerge. I am very glad that this way of thinking is around for us. Bo gave an excellent reply with some details, she is much more knowledgeable than me. Regards, Smita > > > Quote Link to comment Share on other sites More sharing options...
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