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Xenobiotic Metabolism An examination of the fate of foreign compounds (xenobiotics) in biological systems is a natural outgrowth of man’s curiosity about his environment, and his susceptibility to it. While most modern studies concern the fate of drugs in man and animals, there are also investigations into the fate of organic compounds in plants, fruit flies, nematodes and easts. The term “xenobiotic” was coined to cover all compounds that are “foreign” to the organism under study. In some situations, this is loosely defined to include naturally present compounds administered by alternate routes or at “unnatural” concentrations. This historical calendar, a joint project of Bioanalytical Systems, Inc. (BAS) and the International Society for the Study of Xenobiotics (ISSX), portrays some of the pioneering studies in xenobiotic

metabolism during the past two centuries. There is much more science behind these stories, and this will be posted on the ISSX web site at www.issx.org. The information presented in this calendar is posted on the BAS web site (along with past historical calendars on chemistry, electrochemistry and pharmaceutical companies) at www.bioanalytical.com. credits Index | Intro | The Beginning | OxidationSulfation | Glucuronides | Acetylation, MethylationReduction | Mercapturic Acid | Founding of the FieldDrug Metabolism Methodology | In Vitro Technology | P-450 The

Future amy, you are right they are fos...basically when an etoh molecule hits the liver one of only 3 things can happen.. 1)the usual,oxidation,dehydrogentation,with ADH,happening in 198/200 etoh moles. 2)the very unusual,glucuronidation,forming EtG...1/200 etoh molecules... 3)the other very unusual,sulfation,forming EtS.....1/200 etoh molecules... the tests are different,not confirmatory,too rare to ever really indicate much of anything at low level to really say what is going on because of endogenous ETOH...regards,r amykellog <amykellog@...> wrote: So does that mean that ets is really "confirmatory?" Or are they just saying that cause theoretically it sounds good and they are supposed to HAVE a "confirmatory" type test? Isn't it like comparing two different things? And when we get told that we have a + etg, does that automatically mean that we have a + ets (except for 5%?) Don't mean to sound stupid, just don't quite understand...>> EtS is another metabolic product of ethanol that is produced by a group of enzymes under

different genetic control than is the UGT enzyme system. US Drug Testing Labs does confirmatory EtG/EtS panels for LabCorp for all their positive specimens. Here's their rationale for the dual assay...to remove any possible doubt as to whether a specimen is truly positive and to remove the bacterial glucuronidase destruction of EtG as a re-confirmation barrier. Also, if you are testing positive for EtG because you are a hyperproducer of EtG (i.e. genetically predisposed or upregulation of the enzyme system by meds like Tylenol or estrogens), you may actually test below the threshold cutoff for EtS but test positive for EtG. According to USDTL, EtS is present along with EtG in about 95% of the positive specimens they report out.> > EtG and EtS> > > I don't know much about this, so I'm asking the group. I tested today > (great) and the lab owner said thy use EtG but follow it up wth an EtS > as a confirmation test. Why not just do the EtS alone? Do our labs > do both? I don't think so. Is the EtS more specific and if so, why > do all our labs do EtG only? When both are done, is the 2nd one at > the lab's expense? It always comes down to money with them-doesn't > it? > > I really apprciate any informtion anyone can give me on this--I'm just > curious to learn as much as I can about this and the motivations > behind their choices (money).>

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thanks amy,it helps me to think of the liver as the giant singles bar of the body where all lonely etoh molecules go to party...most leave out the front..every once in a while a few go out back and get conjugated with the the punk rock duo gluco and sulfo who always have a gig going way in the back...regards,r amykellog <amykellog@...> wrote: Thanks for clarifying Robin, you rock.> >> > EtS is another metabolic product of ethanol that is produced by a group of enzymes > under different genetic control than is the UGT enzyme system. US Drug Testing Labs does > confirmatory EtG/EtS panels for LabCorp for all their positive specimens. Here's their > rationale for the dual assay...to remove any possible doubt as to whether a specimen is > truly positive and to remove the bacterial glucuronidase destruction of EtG as a re-> confirmation barrier. Also, if you are testing positive for EtG because you are a > hyperproducer of EtG (i.e. genetically predisposed or upregulation of the enzyme system > by meds like Tylenol or estrogens), you may actually test below the threshold cutoff for EtS > but test positive for EtG. According to USDTL, EtS

is present along with EtG in about 95% of > the positive specimens they report out.> > > > EtG and EtS> > > > > > I don't know much about this, so I'm asking the group. I tested today > > (great) and the lab owner said thy use EtG but follow it up wth an EtS > > as a confirmation test. Why not just do the EtS alone? Do our labs > > do both? I don't think so. Is the EtS more specific and if so, why > > do all our labs do EtG only? When both are done, is the 2nd one at > > the lab's expense? It always comes down to money with them-doesn't > > it? > > > > I really

apprciate any informtion anyone can give me on this--I'm just > > curious to learn as much as I can about this and the motivations > > behind their choices (money).> >>

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you are 100% correct gf,glucuronidation and sulfation are the two very similar but different leftover liver biochemical pathways from when we were lower forms kind of like the appendix or the sacrum is a remnant of a tail...they are trivial vestigial pathways not used much but always used a little,maybe .005% of hepatic function, compared to oxidation/deydrogenation with ADH unless that pathway is blocked by a drug(different psych drugs) or liver damage such that the glucuronide and sulfide pumps are primed and become upregulated(apap)...as such one test has much the same pitfalls as the the other...the bottom line is that both tests have too much exponential variability at low levels to be a true reflection of liver etoh metabolism per lorie's recent post of up to 15X variability,so that even values upwardsof 2500 ng/ml are in theory statistically possible..if you will search the history of xenobiology it is most interesting how

these pathways were discovered per my recent post below..i am just plain robin by the way..if i am fos call me on it...degrees are like baby thermometers here,you know what we do with those...regards,r giantsfan70191 <flamingo@...> wrote: Dr. Murray,I am not at all well-versed with regards to the other possible biomarkers for alcohol consumption but, based on what you are saying, it sounds as if, in theory, EtS would have the same pitfalls as EtG. Please correct me if I

am mistaken.>> Xenobiotic Metabolism> An examination of the fate of foreign compounds (xenobiotics) in biological systems is a natural outgrowth of man's curiosity about his environment, and his susceptibility to it. While most modern studies concern the fate of drugs in man and animals, there are also investigations into the fate of organic compounds in plants, fruit flies, nematodes and easts. The term "xenobiotic" was coined to cover all compounds that are "foreign" to the organism under study. In some situations, this is loosely defined to include naturally present compounds administered by alternate routes or at "unnatural" concentrations.> This historical calendar, a joint project of Bioanalytical Systems, Inc. (BAS) and the

International Society for the Study of Xenobiotics (ISSX), portrays some of the pioneering studies in xenobiotic metabolism during the past two centuries. There is much more science behind these stories, and this will be posted on the ISSX web site at www.issx.org. The information presented in this calendar is posted on the BAS web site (along with past historical calendars on chemistry, electrochemistry and pharmaceutical companies) at www.bioanalytical.com.> credits> > ---------------------------------> Index | Intro | The Beginning | Oxidation> Sulfation | Glucuronides | Acetylation, Methylation> Reduction | Mercapturic Acid | Founding of the Field> Drug Metabolism Methodology | In Vitro Technology | P-450 > The Future> > amy, you are right they are fos...basically when an etoh molecule hits the liver> one of only 3 things can happen..>

> 1)the usual,oxidation,dehydrogentation,with ADH,happening in 198/200 etoh moles.> > 2)the very unusual,glucuronidation,forming EtG...1/200 etoh molecules...> > 3)the other very unusual,sulfation,forming EtS.....1/200 etoh molecules...> > the tests are different,not confirmatory,too rare to ever really indicate much of anything at low level to really say what is going on because of endogenous ETOH...regards,r > >

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I love it!robin murray <remurraymd@...> wrote: thanks amy,it helps me to think of the liver as the giant singles bar of the body where all lonely etoh molecules go to party...most leave out the front..every once in a while a few go out back and get conjugated with the the punk rock duo gluco and sulfo who always have a gig going way in the back...regards,r amykellog <amykellog > wrote: Thanks for clarifying Robin, you rock.> >> > EtS is another metabolic product of ethanol that is produced by a group of enzymes > under different genetic control than is the UGT enzyme system. US Drug Testing Labs does > confirmatory EtG/EtS panels for LabCorp for all their positive specimens. Here's their > rationale for the dual assay...to remove any possible doubt as to whether a specimen is > truly positive and to remove the bacterial glucuronidase destruction of EtG as a re-> confirmation barrier. Also, if you are testing positive for EtG because you are a > hyperproducer of EtG (i.e. genetically predisposed or upregulation of the enzyme system > by meds like Tylenol or estrogens), you

may actually test below the threshold cutoff for EtS > but test positive for EtG. According to USDTL, EtS is present along with EtG in about 95% of > the positive specimens they report out.> > > > EtG and EtS> > > > > > I don't know much about this, so I'm asking the group. I tested today > > (great) and the lab owner said thy use EtG but follow it up wth an EtS > > as a confirmation test. Why not just do the EtS alone? Do our labs > > do both? I don't think so. Is the EtS more specific and if so, why > > do all our labs do EtG only? When both are done, is the 2nd one at > > the

lab's expense? It always comes down to money with them-doesn't > > it? > > > > I really apprciate any informtion anyone can give me on this--I'm just > > curious to learn as much as I can about this and the motivations > > behind their choices (money).> >>

Get your own web address for just $1.99/1st yr. We'll help. Small Business.

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the back door men marsha...men don't know but little girls understand...sorry channeling jim morrison today...thanks,regards,rMarsha Dienelt <marshadienelt@...> wrote: I love it!robin murray <remurraymd > wrote: thanks amy,it helps me to think of the liver as the giant singles bar of the body where all lonely etoh molecules go to

party...most leave out the front..every once in a while a few go out back and get conjugated with the the punk rock duo gluco and sulfo who always have a gig going way in the back...regards,r amykellog <amykellog > wrote: Thanks for clarifying Robin, you rock.> >> > EtS is another metabolic product of ethanol that is produced by a group of enzymes > under different genetic control than is the UGT enzyme system. US Drug Testing Labs does > confirmatory EtG/EtS panels for LabCorp for all their positive specimens. Here's their > rationale for the dual assay...to remove any possible doubt as to whether a specimen

is > truly positive and to remove the bacterial glucuronidase destruction of EtG as a re-> confirmation barrier. Also, if you are testing positive for EtG because you are a > hyperproducer of EtG (i.e. genetically predisposed or upregulation of the enzyme system > by meds like Tylenol or estrogens), you may actually test below the threshold cutoff for EtS > but test positive for EtG. According to USDTL, EtS is present along with EtG in about 95% of > the positive specimens they report out.> > > > EtG and EtS> > > > > > I don't know much about this, so I'm asking the group. I tested today > >

(great) and the lab owner said thy use EtG but follow it up wth an EtS > > as a confirmation test. Why not just do the EtS alone? Do our labs > > do both? I don't think so. Is the EtS more specific and if so, why > > do all our labs do EtG only? When both are done, is the 2nd one at > > the lab's expense? It always comes down to money with them-doesn't > > it? > > > > I really apprciate any informtion anyone can give me on this--I'm just > > curious to learn as much as I can about this and the motivations > > behind their choices (money).> >> Get your own web address for just $1.99/1st yr. We'll help. Small Business.

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lyrics to a song lorie before your time in the sixties by the doors called back door man by jim morrison,sorry to be so tangential and wierd and off topic but my mind works like that,free association stuff...just my whatever,ignore me,i will pass..regards,rLorie <lorieg@...> wrote: You lost me, Robin. I don't get it...> > >> > > EtS is another metabolic product of ethanol that is produced by agroup of enzymes> > under different genetic control than is the UGT enzyme system. USDrug Testing Labs> does> > confirmatory EtG/EtS panels for LabCorp for all their positivespecimens. Here's their> > rationale for the dual assay...to remove any possible doubt as towhether a specimen is> > truly positive and to remove the bacterial glucuronidase destructionof EtG as a re-> > confirmation barrier. Also, if you are testing positive for EtGbecause you are a> > hyperproducer of EtG (i.e. genetically predisposed or upregulationof the enzyme system> > by meds like Tylenol or estrogens), you may actually test

below thethreshold cutoff for> EtS> > but test positive for EtG. According to USDTL, EtS is present alongwith EtG in about 95%> of> > the positive specimens they report out.> > >> > > EtG and EtS> > >> > >> > > I don't know much about this, so I'm asking the group. I testedtoday> > > (great) and the lab owner said thy use EtG but follow it up wth anEtS> > > as a confirmation test. Why not just do the EtS alone? Do our labs> > > do both? I don't think so. Is the EtS more specific and if so, why> > > do all our labs do

EtG only? When both are done, is the 2nd one at> > > the lab's expense? It always comes down to money with them-doesn't> > > it?> > >> > > I really apprciate any informtion anyone can give me on this--I'mjust> > > curious to learn as much as I can about this and the motivations> > > behind their choices (money).> > >> >>>>>>>>>>> ---------------------------------> Get your own web address for just $1.99/1st yr. We'll help. Small Business.>

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Robin, In Dr. Skipper's discussion group we had our theme song to the Gilligan's Island' song....you would have absouletly LOVED it!! robin murray <remurraymd@...> wrote: lyrics to a song lorie before your time in the sixties by the doors called back door man by jim morrison,sorry to be so tangential and wierd and off topic but my mind works like that,free association stuff...just my whatever,ignore me,i will pass..regards,rLorie <lorieglanset>

wrote: You lost me, Robin. I don't get it...> > >> > > EtS is another metabolic product of ethanol that is produced by agroup of enzymes> > under different genetic control than is the UGT enzyme system. USDrug Testing Labs> does> > confirmatory EtG/EtS panels for LabCorp for all their positivespecimens. Here's their> > rationale for the dual assay...to remove any possible doubt as towhether a specimen is> > truly positive and to remove the bacterial

glucuronidase destructionof EtG as a re-> > confirmation barrier. Also, if you are testing positive for EtGbecause you are a> > hyperproducer of EtG (i.e. genetically predisposed or upregulationof the enzyme system> > by meds like Tylenol or estrogens), you may actually test below thethreshold cutoff for> EtS> > but test positive for EtG. According to USDTL, EtS is present alongwith EtG in about 95%> of> > the positive specimens they report out.> > >> > > EtG and EtS> > >> > >> > > I don't know much about this, so I'm asking the group.

I testedtoday> > > (great) and the lab owner said thy use EtG but follow it up wth anEtS> > > as a confirmation test. Why not just do the EtS alone? Do our labs> > > do both? I don't think so. Is the EtS more specific and if so, why> > > do all our labs do EtG only? When both are done, is the 2nd one at> > > the lab's expense? It always comes down to money with them-doesn't> > > it?> > >> > > I really apprciate any informtion anyone can give me on this--I'mjust> > > curious to learn as much as I can about this and the motivations> > > behind their choices (money).> > >> >>>>>>>>>>> ---------------------------------> Get your own web address for just $1.99/1st yr. We'll help. Small

Business.>

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good idee,nancy,a catchy theme song for the group..will have to chew my cud on that a bit...suggestions?regards,rN <nautiques5@...> wrote: Robin, In Dr. Skipper's discussion group we had our theme song to the Gilligan's Island' song....you would have absouletly LOVED it!! robin murray <remurraymd > wrote: lyrics

to a song lorie before your time in the sixties by the doors called back door man by jim morrison,sorry to be so tangential and wierd and off topic but my mind works like that,free association stuff...just my whatever,ignore me,i will pass..regards,rLorie <lorieglanset> wrote: You lost me, Robin. I don't get it...> > >> > > EtS is another metabolic product of ethanol that is produced by agroup of enzymes> > under different genetic control than is the UGT

enzyme system. USDrug Testing Labs> does> > confirmatory EtG/EtS panels for LabCorp for all their positivespecimens. Here's their> > rationale for the dual assay...to remove any possible doubt as towhether a specimen is> > truly positive and to remove the bacterial glucuronidase destructionof EtG as a re-> > confirmation barrier. Also, if you are testing positive for EtGbecause you are a> > hyperproducer of EtG (i.e. genetically predisposed or upregulationof the enzyme system> > by meds like Tylenol or estrogens), you may actually test below thethreshold cutoff for> EtS> > but test positive for EtG. According to USDTL, EtS is present alongwith EtG in about 95%> of> > the positive specimens they report out.> > >> > > EtG and EtS> > >> > >> > > I don't know much about this, so I'm asking the group. I testedtoday> > > (great) and the lab owner said thy use EtG but follow it up wth anEtS> > > as a confirmation test. Why not just do the EtS alone? Do our labs> > > do both? I don't think so. Is the EtS more specific and if so, why> > > do all our labs do EtG only? When both are done, is the 2nd one at> > > the lab's expense? It always comes down to money with them-doesn't> > > it?> > >> > > I really apprciate any informtion anyone can give me on this--I'mjust> > > curious to learn as much as I can about this and the

motivations> > > behind their choices (money).> > >> >>>>>>>>>>> ---------------------------------> Get your own web address for just $1.99/1st yr. We'll help. Small Business.> Stay in the know. Pulse on the new .com. Check it out.

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