Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcohol is known to be mainly metabolized in the liver by alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2), and cytochrome P-450IIEI. The purpose of this study was to clarify the role of polymorphism of these ethanol-metabolizing enzymes in drinking behavior and the progression of alcoholic liver disease among Japanese men. Polymorphism of the ADH2, ALDH2, and P-45IIEI genes were determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis in 189 normal Japanese men and 26 male patients with alcoholic liver disease. Drinking behavior was estimated by self-assessment according to DSM-III-R criteria. Facial flushing was reported in 91 subjects heterozygous for ALDH2*1/*2 and in two subjects homozygous for ALDH2*2/*2, but was not found in 96 subjects homozygous for ALDH2*1/*1. In contrast, polymorphism of ADH2 and P-450IIEI did not differ between flushers and nonflushers. Although the flushers only drank a small amount of alcohol (< 20 g of ethanol/day), the nonflushers were divided into a group of moderate drinkers (20 to 80 g/day; n = 54) and a group of heavy drinkers (> 80 g/day; n = 42). A high preponderance of heterozygosity for the ADH2*1/*2 genes (20/42; 60%) and a high frequency of the ADH2*1 allele were found in heavy drinkers, compared with moderate drinkers. However, cytochrome P-45IIEI gene polymorphism was similar among the moderate and heavy drinkers. Not only a high frequency of the ALDH2*1 and ADH2*1 alleles, but also a high frequency of the P-450IIEI c2 allele was found in the patients with alcoholic liver disease. From these results, the drinking behavior of Japanese men is strongly influenced by the ALDH2*1 allele, and the level of alcohol intake is affected by the ADH2*1 allele, but not by cytochrome P-45IIEI. However, progression to alcoholic liver disease among heavy drinkers may be affected by the cytochrome P-450IIEI c2 allele.
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PMID:Polymorphism of alcohol-metabolizing genes affects drinking behavior and alcoholic liver disease in Japanese men. 919 10

Erectile dysfunction (ED) in men is amenable to correction with Viagra in a majority of patients. The accumulated experience of prescribing Viagra across the broad continuum of men suffering from ED is sufficient for a meaningful assessment of the safety of Viagra in clinical practice. The use of Viagra necessitates caution in cardiac failure and when used within six months of acute myocardial infarction and stroke. It is inadvisable in patients with unstable angina pectoris. The co-administration of Viagra with organic nitrates, for example, glyceryl trinitrate or isosorbide dinitrate, is unsafe. The relative contraindications to Viagra in cardiovascular disease are uncontrolled hypertension and impaired cardiac reserve. With respect to interactions with other drugs, the potential influence on the metabolism of Viagra by medications that affect the cytochrome-P-450 system does not translate into clinical effects. The vasodilatory properties of sildenafil citrate are largely responsible for unwanted effects. The most common side effects are headache, flushing (due to vasodilation), and dyspepsia (due to relaxation of the smooth muscle of the gastroesophageal sphincter with reflux). In the recommended single-dose range (25-100 mg), the use of Viagra for erectile dysfunction, in the absence of contraindications, is extremely safe provided the drug is taken under proper conditions.
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PMID:The clinical safety of viagra. 1207 89

Two water quality monitoring strategies designed to sample hydrophobic organic contaminants have been applied and evaluated across an expected concentration gradient in PAHs in the Moreton region. Semipermeable membrane devices (SPMDs) that sequester contaminants via passive diffusion across a membrane were used to evaluate the concentration of PAHs at four and five sites in spring and summer 2001/2002, respectively. In addition, induction of hepatic cytochrome P4501, EROD activity, in yellowfin bream, Acanthopagrus australis, captured in the vicinity of SPMD sampling sites following deployment in summer was used as a biomarker of exposure to PAHs and related chemicals. SPMDs identified a clear and reproducible gradient in PAH contamination with levels increasing from east to west in Moreton Bay and upstream in the Brisbane River. The highest PAH concentrations expressed as B(a)P-toxicity equivalents (TEQs) were found in urban areas, which were also furthest upstream and experienced the least flushing. Cytochrome P4501 induction in A. australis was similar at all sites. The absence of clear trends in EROD activity may be attributable to factors not measured in this study or variable residency time of A. australis in contaminated areas. It is also possible that fish in the Moreton region are displaying enzymatic adaptation, which has been reported previously for fish subjected to chronic exposure to organic contaminants. These potential interferences complicate interpretation of EROD activity from feral biota. It is, therefore, suggested that future monitoring combine the two methods by applying passive sampler extracts to in vitro EROD assays.
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PMID:Monitoring PAHs in the Brisbane River and Moreton Bay, Australia, using semipermeable membrane devices and EROD activity in yellowfin bream, Acanthopagrus australis. 1517 96

The relationships between the individual (and racial) differences in alcohol metabolism and toxicity, and the genetic polymorphism of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P-4502E1(CYPIIE1) were reviewed. In recent studies involving DNA analysis, it was found that a deficiency of the ALDH2 isozyme (ALDH2*2) was responsible for the flushing symptoms as well as other vasomotor symptoms caused by a higher acetaldehyde level after alcohol consumption. Deficiency of ALDH2 activity has been found prevalently only among people of Mongoloid origin, and the deficiency of ALDH2 prevents them from developing alcohol dependence due to the unpleasant physical effects of the flushing symptom. It was reported that Mongoloids such as Japanese and Chinese people carry the enzymatically active (ALDH2*1) subunit and/or the inactive (ALDH2*2) one, and that a low proportion of ALDH2 deficiency (ALDH2*2 allele frequency) was found in alcoholics compared with healthy controls. It was also reported that polymorphism of ALDH2 and/or CYP2E1 may be associated with the susceptibility to alcohol-induced liver injury. Concerning blood ethanol elimination kinetics, it was reported that the c2 gene of CYP2E1 and the ALDH2*1 gene may have greater effects on ethanol and acetaldehyde elimination than the other genotypes, when the blood ethanol level is below 20 m M.
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PMID:Ethanol metabolism, toxicity and genetic polymorphism. 2673 19