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Laura E Nagy - One of the best experts on this subject based on the ideXlab platform.
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molecular aspects of Alcohol Metabolism transcription factors involved in early ethanol induced liver injury
Annual Review of Nutrition, 2004Co-Authors: Laura E NagyAbstract:▪ Abstract Alcohol Metabolism takes place primarily in the liver. Initial exposures to ethanol have a major impact on the hepatic redox state and intermediary Metabolism as a consequence of ethanol Metabolism via Alcohol dehydrogenase. However, upon continued exposure to ethanol, the progression of liver injury involves ethanol Metabolism via CYP2E1 and consequent oxidant stress, as well as potential direct effects of ethanol on membrane proteins that are independent of ethanol Metabolism. Multiple organ systems contribute to liver injury, including the innate immune system and adipose tissue. In response to ethanol exposure, specific signal transduction pathways, including NFκB and the mitogen-activated protein kinase family members ERK1/2, JNK, and p38, are activated. These complex responses to ethanol exposure translate into activation of nuclear transcription factors and altered gene expression within the liver, leading to the development of steatosis and inflammation in the early stages of Alcohol-in...
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molecular aspects of Alcohol Metabolism transcription factors involved in early ethanol induced liver injury
Annual Review of Nutrition, 2004Co-Authors: Laura E NagyAbstract:Alcohol Metabolism takes place primarily in the liver. Initial exposures to ethanol have a major impact on the hepatic redox state and intermediary Metabolism as a consequence of ethanol Metabolism via Alcohol dehydrogenase. However, upon continued exposure to ethanol, the progression of liver injury involves ethanol Metabolism via CYP2E1 and consequent oxidant stress, as well as potential direct effects of ethanol on membrane proteins that are independent of ethanol Metabolism. Multiple organ systems contribute to liver injury, including the innate immune system and adipose tissue. In response to ethanol exposure, specific signal transduction pathways, including NFkappaB and the mitogen-activated protein kinase family members ERK1/2, JNK, and p38, are activated. These complex responses to ethanol exposure translate into activation of nuclear transcription factors and altered gene expression within the liver, leading to the development of steatosis and inflammation in the early stages of Alcohol-induced liver injury.
John M Morton - One of the best experts on this subject based on the ideXlab platform.
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normal Alcohol Metabolism after gastric banding and sleeve gastrectomy a case cross over trial
Journal of The American College of Surgeons, 2012Co-Authors: Eric Changchien, Gavitt A Woodard, Tina Hernandezboussard, John M MortonAbstract:Background Severe obesity remains the leading public health concern of the industrialized world, with bariatric surgery as the only current effective enduring treatment. In addition to gastric bypass, gastric banding and sleeve gastrectomy have emerged as viable treatment options for the severely obese. Occasionally, poor postoperative psychological adjustment has been reported. It has been previously demonstrated that breath Alcohol content (BAC) levels and time to sober were increased in postoperative gastric bypass patients. The aim of this study was to examine whether Alcohol Metabolism in patients undergoing restrictive-type bariatric procedures is also altered. Study Design Nine patients undergoing laparoscopic adjustable gastric banding (LAGB) and 7 patients undergoing laparoscopic sleeve gastrectomy (LSG) were recruited. Preoperatively, 3-month and 6-month BAC and time to sober were measured after administration of 5 ounces of red wine. In addition, participants were asked to complete a questionnaire of drinking habits. Result The 16 total participants achieved a mean 44.7% 6-month excess weight loss. There were no significant changes in peak BAC or time to sober from preoperative levels (0.033%, 67.8 min, respectively) to 3 months (0.032%, 77.1 min, respectively, p=0.421) or 6 months (0.035%, 81.2 min, respectively, p=0.198). Conclusion Patients undergoing LAGB and LSG do not share the same altered Alcohol Metabolism as seen in gastric bypass patients. However, all bariatric surgery patients should be counseled regarding Alcohol use.
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impaired Alcohol Metabolism after gastric bypass surgery a case crossover trial
Journal of The American College of Surgeons, 2011Co-Authors: Gavitt A Woodard, Tina Hernandezboussard, John Downey, John M MortonAbstract:Background Severe obesity remains the leading public health crisis of the industrialized world, with bariatric surgery the only effective and enduring treatment. Poor psychological adjustment has been occasionally reported postoperatively. In addition, evidence suggests that patients can metabolize Alcohol differently after gastric bypass. Study Design Preoperatively and at 3 and 6 months postoperatively, 19 Roux-en-Y gastric bypass (RYGB) patients' breath Alcohol content (BAC) was measured every 5 minutes after drinking 5 oz red wine to determine peak BAC and time until sober in a case-crossover design preoperatively and at 6 months postoperatively. Results Patients reported symptoms experienced when intoxicated and answered a questionnaire of drinking habits. The peak BAC in patients after RYGB was considerably higher at 3 months (0.059%) and 6 months (0.088%) postoperatively than matched preoperative levels (0.024%). Patients also took considerably more time to return to sober at 3 months (61 minutes) and 6 months (88 minutes) than preoperatively (49 minutes). Postoperative intoxication was associated with lower levels of diaphoresis, flushing, and hyperactivity and higher levels of dizziness, warmth, and double vision. Postoperative patients reported drinking considerably less Alcohol, fewer preferred beer, and more preferred wine than before surgery. Conclusions This is the first study to match preoperative and postoperative Alcohol Metabolism in gastric bypass patients. Post-RYGB patients have much higher peak BAC after ingesting Alcohol and require more time to become sober. Patients who drink Alcohol after gastric bypass surgery should exercise caution.
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does gastric bypass alter Alcohol Metabolism
Surgery for Obesity and Related Diseases, 2007Co-Authors: Judith C Hagedorn, Betsy Encarnacion, Gabriel A Brat, John M MortonAbstract:Abstract Background Morbid obesity is the leading public health crisis in the United States, with bariatric surgery as the only effective and enduring treatment for this disease. a concern has been raised, that, postoperatively, Alcohol Metabolism might be altered in gastric bypass patients. We hypothesized that Alcohol Metabolism in the postoperative gastric bypass patient would be altered. Methods Of 36 subjects, 17 control and 19 postgastric bypass subjects each consumed 5 oz of red wine. They underwent an Alcohol breath analysis every 5 minutes. The outcomes recorded included symptoms, initial peak Alcohol breath level, and the time for Alcohol breath levels to normalize. Results The gastric bypass group was on average 10 years older and had a greater weight and body mass index than the control group. The average time after gastric bypass was 2 years, with an average body mass index loss of 18 kg/m 2 (51 kg/m 2 before versus 33 kg/m 2 after). The gastric bypass patients had a peak Alcohol breath level of 0.08% and the controls had a level of 0.05%. The gastric bypass group needed, on average, 108 minutes to reach an Alcohol breath level of 0; the control group reached this level after an average of 72 minutes. Both groups showed a similar postingestion symptom profile. Conclusion In this study, Alcohol Metabolism was significantly different between the postgastric bypass and control subjects. Although the gastric bypass patients' had a greater peak Alcohol level and a longer time for the Alcohol level to reach 0 than the controls, the gastric bypass group did not experience more symptoms than the control group. These findings provide caution regarding Alcohol use by gastric bypass patients.
Andrew J Birley - One of the best experts on this subject based on the ideXlab platform.
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adh single nucleotide polymorphism associations with Alcohol Metabolism in vivo
Human Molecular Genetics, 2009Co-Authors: Andrew J Birley, Peter A Dickson, Michael R James, Grant W Montgomery, Andrew C. Heath, John WhitfieldAbstract:We have previously found that variation in Alcohol Metabolism in Europeans is linked to the chromosome 4q region containing the ADH gene family. We have now typed 103 single nucleotide polymorphisms (SNPs) across this region to test for allelic associations with variation in blood and breath Alcohol concentrations after an Alcohol challenge. In vivo Alcohol Metabolism was modelled with three parameters that identified the absorption and rise of Alcohol concentration following ingestion, and the rate of elimination. Alleles of ADH7 SNPs were associated with the early stages of Alcohol Metabolism, with additional effects in the ADH1A, ADH1B and ADH4 regions. Rate of elimination was associated with SNPs in the intragenic region between ADH7 and ADH1C, and across ADH1C and ADH1B. SNPs affecting Alcohol Metabolism did not correspond to those reported to affect Alcohol dependence or Alcohol-related disease. The combined SNP associations with early- and late-stage Metabolism only account for approximately 20% of the total genetic variance linked to the ADH region, and most of the variance for in vivo Alcohol Metabolism linked to this region is yet to be explained.
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Association of the gastric Alcohol dehydrogenase gene ADH7 with variation in Alcohol Metabolism
Human molecular genetics, 2007Co-Authors: Andrew J Birley, Peter A Dickson, Michael R James, Grant W Montgomery, Andrew C. Heath, John WhitfieldAbstract:Seven Alcohol-metabolizing enzymes are encoded by the human Alcohol dehydrogenase (ADH) gene cluster on chromosome 4q22-23. One of these genes, ADH7, is uniquely expressed in the stomach mucosa and can influence Metabolism of Alcohol before its absorption into the blood. However, the contribution of ADH7 to the overall genetic variation in Alcohol oxidation in vivo is unknown. Data on in vivo Alcohol Metabolism were obtained for 206 Australian twin pairs of Caucasian ancestry, following ingestion of a standard dose (0.75 g kg(-1) body weight) of Alcohol. Twenty-five single nucleotide polymorphisms that cover the ADH7 encoding region were genotyped. The patterns of linkage disequilibrium among these SNPs identified a recombinational hotspot within intron 7 of the ADH7 gene. A model for the absorption and elimination of Alcohol from the body led to the identification of haplotypes associated with inter-individual variation in the early stages of Alcohol Metabolism. These are within a 35 kb DNA tract contained in the region 5' of intron 7 in the ADH7 gene. The region accounts for 18% of the linkage for Alcohol concentration associated with the ADH region, or approximately 11% of the genetic variance.
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effects of variation at the aldh2 locus on Alcohol Metabolism sensitivity consumption and dependence in europeans
Alcoholism: Clinical and Experimental Research, 2006Co-Authors: Peter A Dickson, John Whitfield, Michael R James, Grant W Montgomery, Andrew C. Heath, Nicholas G Martin, Andrew J BirleyAbstract:Background: The low-activity variant of the aldehyde dehydrogenase 2 (ALDH2) gene found in East Asian populations leads to the Alcohol flush reaction and reduces Alcohol consumption and risk of Alcohol dependence (AD). We have tested whether other polymorphisms in the ALDH2 gene have similar effects in people of European ancestry. Methods: Serial measurements of blood and breath Alcohol, subjective intoxication, body sway, skin temperature, blood pressure, and pulse were obtained in 412 twins who took part in an Alcohol challenge study. Participants provided data on Alcohol reactions, Alcohol consumption, and symptoms related to AD at the time of the study and subsequently. Haplotypes based on 5 single-nucleotide polymorphisms (SNPs) were used in tests of the effects of variation in the ALDH2 gene on Alcohol Metabolism and Alcohol's effects. Results: The typed SNPs were in strong linkage disequilibrium and 2 complementary haplotypes comprised 83% of those observed. Significant effects of ALDH2 haplotype were observed for breath Alcohol concentration, with similar but smaller and nonsignificant effects on blood Alcohol. Haplotype-related variation in responses to Alcohol, and reported Alcohol consumption, was small and not consistently in the direction predicted by the effects on Alcohol concentrations. Conclusions: Genetic variation in ALDH2 affects Alcohol Metabolism in Europeans. However, the data do not support the hypothesis that this leads to effects on Alcohol sensitivity, consumption, or risk of dependence.
John Whitfield - One of the best experts on this subject based on the ideXlab platform.
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adh single nucleotide polymorphism associations with Alcohol Metabolism in vivo
Human Molecular Genetics, 2009Co-Authors: Andrew J Birley, Peter A Dickson, Michael R James, Grant W Montgomery, Andrew C. Heath, John WhitfieldAbstract:We have previously found that variation in Alcohol Metabolism in Europeans is linked to the chromosome 4q region containing the ADH gene family. We have now typed 103 single nucleotide polymorphisms (SNPs) across this region to test for allelic associations with variation in blood and breath Alcohol concentrations after an Alcohol challenge. In vivo Alcohol Metabolism was modelled with three parameters that identified the absorption and rise of Alcohol concentration following ingestion, and the rate of elimination. Alleles of ADH7 SNPs were associated with the early stages of Alcohol Metabolism, with additional effects in the ADH1A, ADH1B and ADH4 regions. Rate of elimination was associated with SNPs in the intragenic region between ADH7 and ADH1C, and across ADH1C and ADH1B. SNPs affecting Alcohol Metabolism did not correspond to those reported to affect Alcohol dependence or Alcohol-related disease. The combined SNP associations with early- and late-stage Metabolism only account for approximately 20% of the total genetic variance linked to the ADH region, and most of the variance for in vivo Alcohol Metabolism linked to this region is yet to be explained.
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Association of the gastric Alcohol dehydrogenase gene ADH7 with variation in Alcohol Metabolism
Human molecular genetics, 2007Co-Authors: Andrew J Birley, Peter A Dickson, Michael R James, Grant W Montgomery, Andrew C. Heath, John WhitfieldAbstract:Seven Alcohol-metabolizing enzymes are encoded by the human Alcohol dehydrogenase (ADH) gene cluster on chromosome 4q22-23. One of these genes, ADH7, is uniquely expressed in the stomach mucosa and can influence Metabolism of Alcohol before its absorption into the blood. However, the contribution of ADH7 to the overall genetic variation in Alcohol oxidation in vivo is unknown. Data on in vivo Alcohol Metabolism were obtained for 206 Australian twin pairs of Caucasian ancestry, following ingestion of a standard dose (0.75 g kg(-1) body weight) of Alcohol. Twenty-five single nucleotide polymorphisms that cover the ADH7 encoding region were genotyped. The patterns of linkage disequilibrium among these SNPs identified a recombinational hotspot within intron 7 of the ADH7 gene. A model for the absorption and elimination of Alcohol from the body led to the identification of haplotypes associated with inter-individual variation in the early stages of Alcohol Metabolism. These are within a 35 kb DNA tract contained in the region 5' of intron 7 in the ADH7 gene. The region accounts for 18% of the linkage for Alcohol concentration associated with the ADH region, or approximately 11% of the genetic variance.
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effects of variation at the aldh2 locus on Alcohol Metabolism sensitivity consumption and dependence in europeans
Alcoholism: Clinical and Experimental Research, 2006Co-Authors: Peter A Dickson, John Whitfield, Michael R James, Grant W Montgomery, Andrew C. Heath, Nicholas G Martin, Andrew J BirleyAbstract:Background: The low-activity variant of the aldehyde dehydrogenase 2 (ALDH2) gene found in East Asian populations leads to the Alcohol flush reaction and reduces Alcohol consumption and risk of Alcohol dependence (AD). We have tested whether other polymorphisms in the ALDH2 gene have similar effects in people of European ancestry. Methods: Serial measurements of blood and breath Alcohol, subjective intoxication, body sway, skin temperature, blood pressure, and pulse were obtained in 412 twins who took part in an Alcohol challenge study. Participants provided data on Alcohol reactions, Alcohol consumption, and symptoms related to AD at the time of the study and subsequently. Haplotypes based on 5 single-nucleotide polymorphisms (SNPs) were used in tests of the effects of variation in the ALDH2 gene on Alcohol Metabolism and Alcohol's effects. Results: The typed SNPs were in strong linkage disequilibrium and 2 complementary haplotypes comprised 83% of those observed. Significant effects of ALDH2 haplotype were observed for breath Alcohol concentration, with similar but smaller and nonsignificant effects on blood Alcohol. Haplotype-related variation in responses to Alcohol, and reported Alcohol consumption, was small and not consistently in the direction predicted by the effects on Alcohol concentrations. Conclusions: Genetic variation in ALDH2 affects Alcohol Metabolism in Europeans. However, the data do not support the hypothesis that this leads to effects on Alcohol sensitivity, consumption, or risk of dependence.
Ronald G. Thurman - One of the best experts on this subject based on the ideXlab platform.
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glycine prevents Alcohol induced liver injury by decreasing Alcohol in the rat stomach
Gastroenterology, 1996Co-Authors: Yuji Iimuro, Donald T Forman, Blair U Bradford, Ronald G. ThurmanAbstract:Abstract BACKGROUND & AIMS: Inactivation of Kupffer cells prevents Alcohol- induced liver injury, and hypoxia subsequent to a hypermetabolic state caused by activated Kupffer cells probably is involved in the mechanism. Glycine is known to prevent hepatic reperfusion injury. The purpose of this study was to determine whether glycine prevents Alcohol- induced liver injury in vivo. METHODS: Male Wistar rats were exposed to ethanol (10-12 g.kg-1.day-1) continuously for up to 4 weeks via an intragastric feeding protocol. The effect of glycine on the first-pass Metabolism of ethanol was also examined in vivo, and the effect on Alcohol Metabolism was estimated specifically in perfused liver. RESULTS: Glycine decreased ethanol concentrations precipitously in urine, breath, peripheral blood, portal blood, feces, and stomach contents. Serum aspartate amino-transferase levels were elevated to 183 U/L after 4 weeks of ethanol-treatment. In contrast, values were significantly lower in rats given glycine along with ethanol. Hepatic steatosis and necrosis also were reduced significantly by glycine. Glycine dramatically increased the first-pass elimination of ethanol in vivo but had no effect on Alcohol Metabolism in the perfused liver. CONCLUSIONS: Glycine minimizes Alcohol-induced liver injury in vivo by preventing ethanol from reaching the liver by activating first-pass Metabolism in the stomach. (Gastroenterology 1996 May;110(5):1536-42)
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4 methylpyrazole inhibits fatty acyl coenzyme synthetase and diminishes catalase dependent Alcohol Metabolism has the contribution of Alcohol dehydrogenase to Alcohol Metabolism been previously overestimated
Molecular Pharmacology, 1993Co-Authors: Blair U Bradford, Donald T Forman, Ronald G. ThurmanAbstract:Alcohol dehydrogenase (ADH)-deficient deer mice were used as an animal model to investigate the effect of 4-methylpyrazole on Alcohol Metabolism. After intraperitoneal dosing of these mutant mice with 4-methylpyrazole, rates of ethanol and methanol Metabolism in vivo were decreased significantly, by 41% and 35%, respectively. In perfused liver, rates of ethanol Metabolism were also decreased up to 61% by 100 microM 4-methylpyrazole. Further, when livers were perfused with methanol, a selective substrate for catalase, rates of methanol Metabolism were decreased by 64% by 4-methylpyrazole. It was further determined that 4-methylpyrazole administration caused negligible changes in total hepatic catalase activity and in rates of oxidation of ethanol by isolated microsomes; rather, it acts on catalase-dependent Alcohol Metabolism by limiting the supply of H2O2. In this study, 4-methylpyrazole inhibited fatty acyl CoA synthetase competitively in liver homogenates. Fatty acyl CoA synthetase is a key enzyme involved in the supply of substrate for peroxisomal oxidation of Alcohols via catalase-H2O2. When palmitate was studied, rates of formaldehyde production from methanol were reduced competitively by 4-methylpyrazole; however, when the product palmitoyl CoA was used, the addition of 4-methylpyrazole did not alter activity. 4-Methylpyrazole also inhibited fatty acyl CoA synthetase activity measured directly from CoA disappearance. These data indicate that fatty acyl CoA synthetase is inhibited by 4-methylpyrazole, thus reducing the availability of H2O2 for catalase-dependent Alcohol Metabolism. Inhibition of methanol Metabolism in deer mice expressing ADH indicates that this phenomenon also occurs in species with ADH. Taken together, these data support the hypothesis that the contribution of ADH to Alcohol Metabolism may have been previously overestimated.