Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Symptomatic arsenic poisoning is not often seen in occupational exposure settings. Attempted homicide and deliberate long-term poisoning have resulted in chronic toxicity. Skin pigmentation changes, palmar and plantar hyperkeratoses, gastrointestinal symptoms, anemia, and liver disease are common. Noncirrhotic portal hypertension with bleeding esophageal varices, splenomegaly, and hypersplenism may occur. A metallic taste, gastrointestinal disturbances, and Mee's lines may be seen. Bone marrow depression is common. 'Blackfoot disease' has been associated with arsenic-contaminated drinking water in Taiwan; Raynaud's phenomenon and acrocyanosis also may occur. Large numbers of persons in areas of India, Pakistan, and several other countries have been chronically poisoned from naturally occurring arsenic in ground water. Toxic delirium and encephalopathy can be present. CCA-treated wood (chromated copper arsenate) is not a health risk unless burned in fireplaces or woodstoves. Peripheral neuropathy may also occur. Workplace exposure or chronic ingestion of arsenic-contaminated water or arsenical medications is associated with development of skin, lung, and other cancers. Treatment may incklude the use of chelating agents such as dimercaprol (BAL), dimercaptosuccinic acid (DMSA), and dimercaptopanesulfonic acid (DMPS).
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PMID:Chronic arsenic poisoning. 1186 18

Research on alcohol-induced liver hypoxia in experimental and clinical alcoholic liver disease (ALD) over a span of 20 years is reviewed. The data has repeatedly supported a role for hypoxia in the pathogenesis of ALD but little attention has been given to this phenomenon in a clinical setting where intervention strategies could be developed. Liver hypoxia, particularly when blood alcohol levels are high, has been documented in vivo in rats fed ethanol continuously at a constant rate for prolonged periods. In this model of ALD, the liver pathology, the liver metabolism and the gene expression differ when the livers are compared at the peak and trough blood alcohol levels as monitored daily by measuring the urinary alcohol level cycle (UAL). Genes regulated by the hypoxia-inducible factor (HIF) are expressed more at the peaks, and the livers contain more inflammation at the peaks. However, alanine aminotransferase levels are higher at the troughs suggesting that hypoxia occurs at the peaks and reperfusion injury occurs at the troughs. These findings may be relevant to binge drinking-induced liver injury where hypoxia at high BAL is followed by normoxia and reoxygination injury when BAL falls toward zero.
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PMID:The role of hypoxia in the pathogenesis of alcoholic liver disease. 1516 27

The blood alcohol level cycle (BALC) of the intragastric tube feeding model first described by Tsukamoto et al., has three separate essential mechanistic components. The first is the requirement for an intact functioning thyroid. The evidence for this is that propylthiouracil or severance of the pituitary stalk completely prevents the cycle. What happens instead of the cycle is that the blood alcohol level rises to a lethal level when ethanol is given continuously at a dose of 11 g/kg/day by stomach tube. When excess thyroid hormone is given orally it markedly attenuates the cycle because it interferes with the changes in the level of thyroid hormone during the cycle. The second component is norepinephrine. Catecholamines are markedly elevated at the peaks of the cycle. Both propranolol and phenoxybenzamine, which are beta- and alpha-blockers, prevent the cycle. Also, when catecholamines are fed in excess in the form of ephedrine, the cycle is eliminated. The third element essential to the cycle is the generation of NAD to support the oxidation of alcohol by alcohol dehydrogenase. When complex I (NADH dehydrogenase) of the mitochondrial electron transport chain is inhibited by feeding rotenone, the cycle is totally eliminated and blood alcohol levels remain constant at 200 mg/%. Thus NADH increases and NAD decreases at the peak of the cycle. Without the fluxuation of NAD, ADH activity cannot fluctuate during the cycle and the cycle is prevented. The significance of the BALC in the understanding of alcohol liver disease pathogenesis is that there's a marked difference in the gene expression and liver toxicity when the peaks and troughs of the cycle are compared. The expression of 1000+ genes is either two-fold up or down regulated as determined by microarray analysis. At the peaks there is increased liver pathology, especially inflammatory changes in the liver associated with an increase of iNOS expression. The genes responsive to hypoxia inducible factor 1alpha (HIF1alpha) regulation are increased including the expression of erythropoietin, adrenomedullin and adrenergic receptor alpha 1a and d. The expression of prolyl hydroxylase, which destabilizes HIF1alpha, increases when the BAL drops to low levels during the cycle. The level of oxygen, as measured on the surface of the liver, is decreased at the peaks, compared to control livers. The NADH/NAD ratio is markedly increased and ATP levels are markedly decreased at the BAL peaks. Also, endotoxin in the blood is very high at the peaks and very low at the troughs. When the blood alcohol levels fall during the cycle, there is an increase in ALT, suggesting that reoxygenation from the hypoxic state at the peaks causes an ischemic reperfusion injury-like lesion in the liver. At this time there is also an increase in expression of many important enzymes such as manganese SOD. Genes such as c-fos and CTGF are increased in expression. These contrasting findings at the peaks and troughs indicate that the blood alcohol levels, which fluctuate up and down, change the gene expression and the pathology of the liver.
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PMID:The pathogenesis and significance of the urinary alcohol cycle in rats fed ethanol intragastrically. 1634 1