Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most important side-effect of sulfonylureas is hypoglycaemia. According to surveys in Switzerland and in Sweden it occurs at a frequency of about 2 cases per 10,000 treatment years. Mortality is high, about 10%. The syndrome of inappropriate ADH-secretion has been observed almost exclusively during treatment with chlorpropamide. Asymptomatic cases of SIADH-syndrome are quite frequent, hyponatraemia has been observed in 6-10% of diabetics treated with chlorpropamide. The most dangerous side-effect of biguanides is lactic acidosis. It occurs significantly more frequent during treatment with phenformin compared to metformin. Metformin has been reported to lead to lactic acidosis in 0.4 cases per 10,000 treatment years; mortality is about 30%. Mortality of phenformin-associated lactic acidosis is even higher, 70%. Both biguanides, phenformin and metformin, cause relatively frequently vitamin B12-malabsorption (in about 1/3 of the cases). However, symptomatic vitamin B12-deficiency is extremely rare.
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PMID:Incidence of severe sideeffects during therapy with sulfonylureas and biguanides. 386 78

The effect of chronic alcohol consumption on vitamin A metabolism was investigated in male rats. Liquid diets containing five times the NRC requirement for vitamin A and varied levels of ethanol were fed. The vitamin A content of the liver was decreased in rats receiving alcohol. Liver lipids were only slightly elevated in alcohol-fed rats. Hepatic vitamin A storage was also decreased in rats fed 30% calories as alcohol and beta-carotene or vitamin A at the NRC requirement level, but not in rats fed one-sixth the NRC requirement as vitamin A. The activities of alcohol dehydrogenase, NADPH cytochrome c reductase, and retinol dehydrogenase were not altered in hepatic or testicular tissue by the vitamin A or alcohol content of the diet. When an intragastric dose of [3H]retinyl acetate or [14C]beta-carotene was administered, fecal excretion of radioactivity was lower than controls in rats receiving 30% ethanol in the diet for a total of 4 weeks, for 1 week following 7 weeks of control diet consumption, and after an acute dose of ethanol. Recovery of the 3H label was greater in the testes of rats chronically consuming ethanol. When a solution containing [3H]retinyl acetate or [3H]beta-carotene with or without ethanol was injected into intestinal segments, no alterations in absorption of retinyl acetate or beta-carotene due to ethanol occurred. It is concluded that alcohol consumption results in decreased hepatic vitamin A storage, which is not due to the malabsorption of either retinyl acetate or beta-carotene, or to altered activities of several enzymes involved in ethanol and vitamin A metabolism.
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PMID:Effect of chronic alcohol consumption and moderate fat diet on vitamin A status in rats fed either vitamin a or beta-carotene. 668 29

Vitamin A and zinc metabolism are affected both by ethanol and by hepatic cirrhosis. Ethanol causes abnormal dark adaptation by acting as a competitive inhibitor with retinol for alcohol dehydrogenase in the eye. In animals oral ethanol intake results in increased losses of zinc by the urinary and fecal routes. Vitamin A malnutrition in cirrhotics may be caused by poor diet, malabsorption, decreased hepatic vitamin A uptake, and decreased hepatic storage capacity for vitamin A. In some cirrhotic patients zinc deficiency and or protein deficiency may limit the ability to respond to vitamin A. Combined vitamin A and zinc deficiencies are common in cirrhotics and either may result in abnormal dark adaptation or impaired taste and smell. The interaction of these two micro-nutrients must be kept in mind by the clinician caring for alcoholic or alcoholic cirrhotic patients.
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PMID:Vitamin A and zinc metabolism in alcoholism. 700 92

Until the 1960s, liver disease of the alcoholic patient was attributed exclusively to dietary deficiencies. Since then, however, our understanding of the impact of alcoholism on nutritional status has undergone a progressive evolution. Alcohol, because of its high energy content, was at first perceived to act exclusively as 'empty calories' displacing other nutrients in the diet, and causing primary malnutrition through decreased intake of essential nutrients. With improvement in the overall nutrition of the population, the role of primary malnutrition waned and secondary malnutrition was emphasized as a result of a better understanding of maldigestion and malabsorption caused by chronic alcohol consumption and various diseases associated with chronic alcoholism. At the same time, the concept of the direct toxicity of alcohol came to the forefront as an explanation for the widespread cellular injury. Some of the hepatotoxicity was found to result from the metabolic disturbances associated with the oxidation of ethanol via the liver alcohol dehydrogenase (ADH) pathway and the redox changes produced by the generated NADH, which in turn affects the metabolism of lipids, carbohydrates, proteins and purines. Exaggeration of the redox change by the relative hypoxia which prevails physiologically in the perivenular zone contributes to the exacerbation of the ethanol-induced lesions in zone 3. In addition to ADH, ethanol can be oxidized by liver microsomes: studies over the last twenty years have culminated in the molecular elucidation of the ethanol-inducible cytochrome P450IIE1 (CYP2E1) which contributes not only to ethanol metabolism and tolerance, but also to the selective hepatic perivenular toxicity of various xenobiotics. Their activation by CYP2E1 now provides an understanding for the increased susceptibility of the heavy drinker to the toxicity of industrial solvents, anaesthetic agents, commonly prescribed drugs, 'over the counter' analgesics, chemical carcinogens and even nutritional factors such as vitamin A. Ethanol causes not only vitamin A depletion but it also enhances its hepatotoxicity. Furthermore, induction of the microsomal pathway contributes to increased acetaldehyde generation, with formation of protein adducts, resulting in antibody production, enzyme inactivation and decreased DNA repair; it is also associated with a striking impairment of the capacity of the liver to utilize oxygen. Moreover, acetaldehyde promotes glutathione depletion, free-radical mediated toxicity and lipid peroxidation. In addition, acetaldehyde affects hepatic collagen synthesis: both in vivo and in vitro (in cultured myofibroblasts and lipocytes), ethanol and its metabolite acetaldehyde were found to increase collagen accumulation and mRNA levels for collagen. This new understanding of the pathogenesis of alcoholic liver disease may eventually improve therapy with drugs and nutrients.
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PMID:Aetiology and pathogenesis of alcoholic liver disease. 821 1

Alcohol causes primary malnutrition by displacing nutrients in the diet and secondary malnutrition via malabsorption and cellular injury through direct cytotoxicity. Hepatotoxicity results from metabolic disturbances associated with the oxidation of ethanol via liver alcohol dehydrogenase (ADH) and the redox changes produced by the generated NADH (the reduced form of nicotinamide adenine dinucleotide), which in turn affects the metabolism of lipids, carbohydrates, proteins, and purines. Ethanol is also oxidized in liver microsomes by an ethanol-inducible cytochrome P450, which contributes to the alcoholic's tolerance and his increased vulnerability to the toxicity of industrial solvents, anesthetics, commonly prescribed drugs, over-the-counter analgesics, chemical carcinogens, and retinoids. Increased acetaldehyde generation, with formation of protein adducts, results in antibody production, enzyme inactivation, decreased DNA repair, impaired utilization of oxygen, glutathione depletion, free radical-mediated toxicity, lipid peroxidation, and increased collagen synthesis. Therapy may eventually improve with the use of supernutrients such as S-adenosyl-L-methionine, which replenishes glutathione, restores methylation, and attenuates liver injury, as well as dilinoleoylphosphatidylcholine, which prevents cirrhosis.
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PMID:Herman Award Lecture, 1993: a personal perspective on alcohol, nutrition, and the liver. 823 56