The Experts below are selected from a list of 186 Experts worldwide ranked by ideXlab platform
Jeffrey Brent - One of the best experts on this subject based on the ideXlab platform.
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Current Management of Ethylene Glycol Poisoning
Drugs, 2001Co-Authors: Jeffrey BrentAbstract:Ethylene glycol, a common antifreeze, coolant and industrial solvent, is responsible for many instances of accidental and intentional poisoning annually. Following ingestion, ethylene glycol is first hepatically metabolised to glycoaldehyde by alcohol dehydrogenase. Glycoaldehyde is then oxidised to glycolic acid, glyoxylic acid and finally oxalic acid. While ethylene glycol itself causes intoxication, the accumulation of toxic metabolites is responsible for the potentially fatal acidosis and renal failure, which characterises ethylene glycol poisoning. Treatment of ethylene glycol poisoning consists of emergent stabilisation, correction of metabolic acidosis, inhibition of further metabolism and enhancing elimination of both unmetabolised parent compound and its metabolites. The prevention of ethylene glycol metabolism is accomplished by the use of antidotes that inhibit alcohol dehydrogenase. Historically, this has been done with intoxicating doses of ethanol. At a sufficiently high concentration, ethanol saturates alcohol dehydrogenase, preventing it from acting on ethylene glycol, thus allowing the latter to be excreted unchanged by the kidneys. However, ethanol therapy is complicated by its own inherent toxicity, and the need to carefully monitor serum ethanol concentrations and adjust the rate of administration. A recent alternative to ethanol therapy is fomepizole, or 4-methylpyrazole. Like ethanol, fomepizole inhibits alcohol dehydrogenase; however it does so without producing serious adverse effects. Unlike ethanol, fomepizole is metabolised in a predictable manner, allowing for the use of a standard, validated administration regimen. Fomepizole therapy eliminates the need for the haemodialysis that is required in selected patients who are non-acidotic and have adequate renal function.
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glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning meta study group
Clinical Toxicology, 1998Co-Authors: C L Moreau, Susan R Rose, Marsha Ford, Kenneth E. Mcmartin, William Kerns, Christian Tomaszewski, Jeffrey BrentAbstract:AbstractObjective: Toxic manifestations following ethylene glycol exposure are due to accumulation of metabolites, particularly glycolate. We characterized glycolate elimination kinetics and dialysis properties in a series of ethylene glycol poisonings. Methods: Patients who ingested ethylene glycol and received fomepizole (4-methylpyrazole; 4-MP) ± hemodialysis were prospectively evaluated. Serial blood samples for ethylene glycol, glycolate, pH, and bicarbonate were drawn to determine glycolate elimination rate, t½, and correlations between initial glycolate and initial markers of acidosis. Dialyzer inlet and outlet samples were obtained to measure hemodialysis glycolate clearance. Plasma ethylene glycol and glycolate were determined by gas chromatography. Results: Ten patients, mean age 49 years (range 28–73 years), presented a mean of 10.5 hours (range 3.5–21.5 hours) after ethylene glycol ingestion. Mean initial ethylene glycol was 18.5 mmol/L (range 0.8–62.2 mmol/L) (115 mg/dL; range 5–386 mg/dL) an...
Anders Helander - One of the best experts on this subject based on the ideXlab platform.
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studies on the interaction between ethanol and serotonin metabolism in rat using deuterated ethanol and 4 methylpyrazole
Biochemical Pharmacology, 2000Co-Authors: Margareta Some, Stefan Svensson, Janolov Hoog, Anders HelanderAbstract:Abstract The metabolic interaction between ethanol and serotonin (5-hydroxytryptamine) via alcohol dehydrogenase (ADH; EC 1.1.1.1) was studied in tissue homogenates of Sprague–Dawley rats by following the transfer of deuterium from deuterated ethanol over endogenous NADH to 5-hydroxytryptophol (5HTOL). Homogenates of whole brain, lung, spleen, kidney, liver, stomach, jejunum, ileum, colon, and caecum were incubated in the presence of [ 2 H 2 ]ethanol and 5-hydroxyindole-3-acetaldehyde (5HIAL), and the [ 2 H]5HTOL formed was identified and quantified using gas chromatography–mass spectrometry. ADH activity was most abundant in liver, kidney, and within the gastrointestinal tract. The highest incorporation of deuterium was obtained in homogenates of kidney, lung, and colon, whereas in brain, which contains very low ADH activity, no incorporation could be demonstrated. Addition of extra NAD + (2.4 mM) increased the formation of [ 2 H]5HTOL 2.6-fold in liver homogenates, but only 1.2-fold in kidney homogenates. 4-Methylpyrazole, a potent inhibitor of class I ADH, inhibited the 5HIAL reduction in homogenates of lung, kidney, jejunum, ileum, and colon, and caused a marked drop in 5HTOL oxidation in all tissues except stomach and spleen. These results demonstrate that in the rat a metabolic interaction between ethanol and serotonin via the ADH pathway may take place in several tissues besides the liver, which is the main tissue for ethanol detoxification.
Shih-jiun Yin - One of the best experts on this subject based on the ideXlab platform.
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Oxidation of methanol, ethylene glycol, and isopropanol with human alcohol dehydrogenases and the inhibition by ethanol and 4-methylpyrazole
Chemico-Biological Interactions, 2011Co-Authors: Shou Lun Lee, Hsuan Ting Shih, Yu Chou Chi, Yeung Pin Li, Shih-jiun YinAbstract:Human alcohol dehydrogenases (ADHs) include multiple isozymes with broad substrate specificity and ethnic distinct allozymes. ADH catalyzes the rate-limiting step in metabolism of various primary and secondary aliphatic alcohols. The oxidation of common toxic alcohols, that is, methanol, ethylene glycol, and isopropanol by the human ADHs remains poorly understood. Kinetic studies were performed in 0.1 M sodium phosphate buffer, at pH 7.5 and 25°C, containing 0.5 mM NAD+and varied concentrations of substrate. KMvalues for ethanol with recombinant human class I ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, and ADH1C2, and class II ADH2 and class IV ADH4 were determined to be in the range of 0.12-57 mM, for methanol to be 2.0-3500 mM, for ethylene glycol to be 4.3-2600 mM, and for isopropanol to be 0.73-3400 mM. ADH1B3 appeared to be inactive toward ethylene glycol, and ADH2 and ADH4, inactive with methanol. The variations for Vmaxfor the toxic alcohols were much less than that of the KMacross the ADH family. 4-Methylpyrazole (4MP) was a competitive inhibitor with respect to ethanol for ADH1A, ADH1B1, ADH1B2, ADH1C1 and ADH1C2, and a noncompetitive inhibitor for ADH1B3, ADH2 and ADH4, with the slope inhibition constants (Kis) for the whole family being 0.062-960 μM and the intercept inhibition constants (Kii), 33-3000 μM. Computer simulation studies using inhibition equations in the presence of alternate substrate ethanol and of dead-end inhibitor 4MP with the determined corresponding kinetic parameters for ADH family, indicate that the oxidation of the toxic alcohols up to 50 mM are largely inhibited by 20 mM ethanol or by 50 μM 4MP with some exceptions. The above findings provide an enzymological basis for clinical treatment of methanol and ethylene glycol poisoning by 4MP or ethanol with pharmacogenetic perspectives. © 2010 Elsevier Ireland Ltd.
N Juranic - One of the best experts on this subject based on the ideXlab platform.
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metal complexes with pyrazole derived ligands part i synthesis and crystal structures of 3 amino 4 acetyl 5 methylpyrazole l and of the tetrahedral complexes znl2 no3 2 and ml2cl2 m cu ii hg ii
Inorganica Chimica Acta, 1991Co-Authors: A Hergoldbrundic, Branko Kaitner, Boris Kamenar, Vukadin M Leovac, E Z Iveges, N JuranicAbstract:A new pyrazole-derived ligand 3-amino-4-acetyl-5-methylpyrazole (L) has been synthesized and structurally characterized. In order to examine its coordination properties the metal complexes ZnL2(NO3)2, CuL2Cl2 and HgL2Cl2 have been prepared and their crystal and molecular structures determined by X-ray structure analysis. The crystals of the ligand are triclinic, space group P with unit cell dimensions a=14.433(4), b=7.406(1), c=6.794(4) A, α=99.81(4), β=92.10(9), γ=105.55(6)°, V= 686.8(5) A3; ZnL2(NO3)2 is orthorhombic, space group Pbca,a=18.420(2), b=14.892(2), c=14.114(2) A, V=3872(1) A3; CuL2Cl2 is monoclinic, space group I2/a,a=13.804(3), b=8.835(1), c=14.264(4) A, β=100.50(3)°, V=1710.5(7) A3; HgL2Cl2 is monoclinic, space group I2/a,a=14.075(2), b=9.002(2), c=14.303(3) A, β=97.39(2)°, V=1797.2(6) A3. The two latter complexes are isostructural. The ligand L acts as a monodentate ligand through the tertiary ring nitrogen atom. The complexes contain metal atoms in the distorted tetrahedral coordination realized by two nitrogen atoms from the two ligands L and two nitrate-oxygen atoms in the zinc complex and two chlorine atoms in the copper and mercury complexes. All four structures are built up from individual molecules linked together by hydrogen bonding interactions NH…O achieved between ‘pyrrole’ ring nitrogens of one molecule and the acetyl-oxygen atoms from the adjacent molecules. In the free ligand the additional hydrogen bondings NH…N occur also between amino and ‘pyridine’ nitrogen atoms of the neighboring molecules. The general physicochemical characteristics as well as the IR and 1H NMR spectra are in accordance with the observed molecular structures.
Margareta Some - One of the best experts on this subject based on the ideXlab platform.
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studies on the interaction between ethanol and serotonin metabolism in rat using deuterated ethanol and 4 methylpyrazole
Biochemical Pharmacology, 2000Co-Authors: Margareta Some, Stefan Svensson, Janolov Hoog, Anders HelanderAbstract:Abstract The metabolic interaction between ethanol and serotonin (5-hydroxytryptamine) via alcohol dehydrogenase (ADH; EC 1.1.1.1) was studied in tissue homogenates of Sprague–Dawley rats by following the transfer of deuterium from deuterated ethanol over endogenous NADH to 5-hydroxytryptophol (5HTOL). Homogenates of whole brain, lung, spleen, kidney, liver, stomach, jejunum, ileum, colon, and caecum were incubated in the presence of [ 2 H 2 ]ethanol and 5-hydroxyindole-3-acetaldehyde (5HIAL), and the [ 2 H]5HTOL formed was identified and quantified using gas chromatography–mass spectrometry. ADH activity was most abundant in liver, kidney, and within the gastrointestinal tract. The highest incorporation of deuterium was obtained in homogenates of kidney, lung, and colon, whereas in brain, which contains very low ADH activity, no incorporation could be demonstrated. Addition of extra NAD + (2.4 mM) increased the formation of [ 2 H]5HTOL 2.6-fold in liver homogenates, but only 1.2-fold in kidney homogenates. 4-Methylpyrazole, a potent inhibitor of class I ADH, inhibited the 5HIAL reduction in homogenates of lung, kidney, jejunum, ileum, and colon, and caused a marked drop in 5HTOL oxidation in all tissues except stomach and spleen. These results demonstrate that in the rat a metabolic interaction between ethanol and serotonin via the ADH pathway may take place in several tissues besides the liver, which is the main tissue for ethanol detoxification.
