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)

Chronic consumption of substantial amounts of alcohol is not associated with the expected effect on body weight. Isocaloric substitution of carbohydrates by ethanol results in weight loss, and addition of ethanol to an otherwise normal diet does not produce the expected weight gain. This energy deficit cannot be explained by maldigestion or malabsorption but has been attributed to induction of the microsomal ethanol oxidizing system (a metabolic pathway that oxidizes ethanol without associated chemical energy production), increased sympathetic tone and associated thermogenesis, and/or enhanced ATP breakdown (with increased purine catabolism) secondary to the acetate produced from ethanol. All these hypotheses do not fully explain the lack of weight deficit when alcohol is consumed with a very-low-fat diet, which suggests that an alteration in the energy utilization derived from fat plays a major role, possibly through uncoupling of oxidation with phosphorylation in mitochondria damaged by chronic ethanol consumption.
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PMID:Perspectives: do alcohol calories count? 195 30

We examined the relationship between cholesterol synthesis and high affinity low density lipoprotein (LDL) catabolism in freshly isolated mononuclear leukocytes and plasma sterols and apolipoprotein concentrations in three homozygous and one heterozygous subject with sitosterolemia with xanthomatosis and in 12 control subjects. Observations in untreated subjects were compared during therapy with lovastatin or interruption of the enterohepatic circulation of bile acids. Plasma cholesterol, plant sterol, and apolipoprotein B concentrations declined more than 50% in the two homozygous sitosterolemic subjects after ileal bypass surgery. In contrast, plasma cholesterol, plant sterol, and apolipoprotein B concentrations remained constant in a homozygous sitosterolemic subject and declined only 7% in a heterozygous sitosterolemic subject during 20 weeks of lovastatin (40 mg/day) treatment compared to a 28% decrease in similarly treated control subjects. Lovastatin treatment decreased cholesterol synthesis more than 60% but did not increase high affinity catabolism of LDL further in the sitosterolemic cells, compared to a more than 20% rise in control mononuclear leukocytes. Conversely, bile acid malabsorption increased cholesterol synthesis 59%, total hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity 13%, and receptor-mediated LDL degradation 41% in control cells, but did not stimulate cholesterol synthesis or microsomal HMG-CoA reductase activity in sitosterolemic mononuclear leukocytes although receptor-mediated LDL catabolism rose an additional 26%. These results demonstrate a greater than expected decrease in plasma sterols and apolipoprotein B concentrations in sitosterolemic subjects after stimulation of bile acid synthesis because of the inability to up-regulate cholesterol production. We suggest that bile acid-sequestering drugs or ileal exclusion surgery may be more effective treatments to mobilize accumulated sterol deposits and prevent atherosclerosis in this disease.
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PMID:Unexpected failure of bile acid malabsorption to stimulate cholesterol synthesis in sitosterolemia with xanthomatosis. Comparison with lovastatin. 231 63

The interaction of ethanol with drugs and xenobiotics is complex because ethanol can affect any of the following steps; absorption, plasma protein binding, hepatic blood flow, distribution, hepatic uptake of drugs, and phase I and II hepatic metabolism. The ingestion of ethanol can lead to malabsorption of a variety of nutrients and can modify the absorption of various drugs. High concentrations of ethanol in conjunction with aspirin causes gastric mucosal damage. The principal effect of acute ethanol ingestion on drug metabolism is inhibition of microsomal drug metabolism. The synergistic effects of ethanol on central nervous system depressants can be explained by this mechanism. In contrast, chronic ethanol consumption increases mixed function oxidation and drug metabolism. The cross tolerance between ethanol and sedatives in chronic alcoholics may be due to this effect of alcohol. In addition, enhanced production of hepatotoxic products from certain drugs and xenobiotics and an increased activation of procarcinogens to carcinogens can result from this microsomal induction. The increased susceptibility to hepatotoxins and the enhanced carcinogenesis in the alcoholic may be explained by this fact. Other effects of the interaction between drugs and ethanol are the result of changes in organ susceptibility, best demonstrated for the central nervous system. Subsequently, the presence of liver disease has a great effect on drug metabolism in alcoholics.
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PMID:Alcohol effects on drug-nutrient interactions. 390 40

The use of a few microcuries of 14C labelled molecules with very short biological half-life for breath-tests gives no more body irradiation than 10 minutes' exposure to the sun. Yet it provides the gastroenterologist with accurate information. Detection and identification of fat malabsorption are easy when 3 labelled lipids are used. Glycine 1 14C cholate administered orally offers a simple, rapid and effective screening technique for the detection of increased bile salt deconjugation and may provide a valuable diagnostic supplement in the study of steatorrhea after ileal resection, bypass or bacterial overgrowth. The clearance of labelled aminopyrine can be decreased in hepatocellular dysfunction or increased in some alcoholic patients or in patients receiving phenobarbitone. Tracer doses of labelled ethanol were used to study the metabolism of ethanol by the liver in alcoholic patients. Chronic ingestion of alcohol stimulates the activity of microsomal drug-metabolising enzymes in both non-cirrhotic and cirrhotic patients; this response is lost in acute liver damage and in chronic alcoholic disease with severe hepatic dysfunction. The CO2-labelled breath-tests are non-invasive, effective and inexpensive. The forthcoming replacement of 14C by non-radioactive 13C or briefly radioactive 11C will render these tests even more attractive.
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PMID:[Labelled CO2 breath-tests in gastroenterology (author's transl)]. 679

There is enormous potential for drug interactions in patients who, today, often receive many drugs. Antibiotics are prominent amongst the groups of drugs commonly prescribed. Many interactions take place at the absorption stage. Antacids and antidiarrhoeal preparations, in particular, can delay and reduce the absorption of antibiotics such as tetracyclines and clindamycin, by combining with them in the gastrointestinal tract to form chelates or complexes. Other drugs can affect gastric motility, which in turn often controls the rate at which antibiotics are absorbed. Some broad spectrum antibiotics can alter the bacterial flora of the gut which may be related to malabsorption states. The potentiation of toxic side effects of one drug by another is a common type of interaction. Antibiotics which are implicated in this type of interaction are those which themselves possess some toxicity such as aminoglycosides, some cephalosporins, tetracyclines and colistin. Some of the most important adverse interactions with antibiotics are those which involve other drugs which have a low toxicity/efficacy ratio. These include anticoagulants such as warfarin, anticonvulsants such as phenytoin and phenobarbitone and oral antidiabetic drugs like tolbutamide. Risk of interaction arises when the metabolism of these drugs is inhibited by liver microsomal enzyme inhibitors such as some sulphonamides and chloramphenicol, or is enhanced by enzyme inducers such as rifampicin.
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PMID:Adverse antibiotic drug interactions. 699 91

We investigated the relationship between plasma cholestanol (5 alpha-dihydrocholesterol) concentrations and the activity and mRNA levels of cholesterol 7 alpha-hydroxylase, the rate-controlling enzyme for bile acid synthesis, in three female sitosterolemic homozygotes. In this lipid storage disease, large amounts of plant sterols and cholestanol accumulate because of hyperabsorption and endogenous synthesis, respectively. Plasma cholestanol concentrations were 14 times greater in the three sitosterolemic homozygotes than the mean for five control subjects. To investigate the cholestanol biosynthetic pathway, tracer doses of two putative precursors, [1,2-3H]4-cholesten-3-one and [4-14C]7 alpha-hydroxycholesterol were injected intravenously into a homozygote, and radioactivity was sought in cholestanol, bile acids, cholesterol, and sitosterol fractions isolated from plasma and bile. Tritium was concentrated only in cholestanol; neither cholesterol, sitosterol nor bile acids were derived from [1,2-3H]4-cholesten-3-one. In contrast, bile acids were labeled exclusively with 14C from [4-14C]7 alpha-hydroxycholesterol; no 14C radioactivity was detected in cholestanol. Mathematical analysis of specific activity versus time curves for [3H]cholestanol revealed very slow decay, large exchangeable pools, and enhanced synthesis in the sitosterolemic homozygote. Measurements of cholesterol 7 alpha-hydroxylase activity were 39% lower in whole liver microsomes from three sitosterolemic homozygotes that contained 19% plant sterols as compared to the mean value for six control microsomal specimens that contained 0.1% plant sterols. Removal of the excess plant sterols from the microsomes, in vitro, normalized microsomal cholesterol 7 alpha-hydroxylase activity in the homozygotes but did not affect enzyme activity in the controls. Equal amounts of cholesterol 7 alpha-hydroxylase mRNA were detected in the livers of both control and sitosterolemic subjects. Bile acid malabsorption after ileal bypass surgery stimulated cholesterol 7 alpha-hydroxylase activity 78% in sitosterolemic whole liver microsomes and reduced plasma cholesterol, sitosterol, and cholestanol levels 61%, 55% and 91%, respectively, producing a pronounced decrease in the cholestanol/cholesterol ratio without changing the sitosterol/cholesterol ratio. These results demonstrate that increased cholestanol is synthesized from 4-cholesten-3-one and not 7 alpha-hydroxycholesterol in sitosterolemia. Enhanced pools and plasma concentrations are related inversely to hepatic cholesterol 7 alpha-hydroxylase activity. Competitive inhibition of cholesterol 7 alpha-hydroxylase by the large microsomal plant sterol pool diverts cholesterol into cholestanol. Alternatively, stimulating cholesterol 7 alpha-hydroxylase activity after ileal bypass surgery markedly diminished plasma cholestanol levels.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inverse relationship between plasma cholestanol concentrations and bile acid synthesis in sitosterolemia. 785 65

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

For decades, research interest has focused on hypertriglyceridemia and hypercholesterolemia, because of their association with atherosclerosis. Recently, however, increasing attention has been paid to rare hypolipidemic states that can cause adverse consequences in young patients. Studies of genetic disorders of fat transport have afforded new insights into the mechanisms involved in intestinal lipid handling and lipoprotein metabolism. This article reviews briefly the current state of knowledge about inherited lipoprotein deficiencies, including abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease. These disorders share many common characteristics: they all cause fat malabsorption, low levels of circulating lipids and fat-soluble vitamins, failure to thrive in early childhood, ataxic neuropathy and visual impairment. However, their etiology is genetically different. Abetalipoproteinemia is caused by the absence of microsomal transfer protein, whereas hypobetalipoproteinemia is due to defects in the apolipoprotein B gene. The etiopathogenesis of chylomicron retention disease is as yet unexplained. Research on these rare, inherited fat disorders of absorption will continue to provide significant advances in our understanding of human physiology and may yield novel therapeutic approaches to atherosclerosis.
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PMID:The genetic basis of primary disorders of intestinal fat transport. 888 69

There is some controversy as to the effect of ethanol on body weight and alcohol energy contribution to body mass. The aim of this study was to evaluate the effect of alcohol addiction on resting energy expenditure (REE) and body composition. Twelve patients with current alcoholism (A) without severe liver disease or lipid and carbohydrate malabsorption were compared with a group of healthy social drinkers (B) matched for sex, age, and height. Their caloric intake was computed on the basis of a food diary. REE was measured with indirect calorimetry, and body composition was assessed by both anthropometry and bioimpedance. A significant decrease in fat mass in A compared with B was found (14.8 +/- 5.39 vs. 19.0 +/- 3.50 kg; p < 0.05). No significant differences were observed in fat-free mass (FFM) or in total body water between the two groups. A showed higher REE values normalized by FFM than B (35.5 +/- 2.97 vs. 33.0 +/- 2.95 kcal/kgFFM; p < 0.05). The nonprotein respiratory quotient was significantly lower in A than in B (0.76 +/- 0.03 vs. 0.86 +/- 0.03; p < 0.001), and A showed significantly higher lipid oxidation and lower carbohydrate oxidation than B (p < 0.05). The daily caloric intake provided only by food ingestion was found to be significantly higher in controls, but because the percentage of alcohol calories of total energy intake was 46.3 +/- 6.80 in alcoholics and 13.6 +/- 3.59 in controls (p < 0.0001), the total caloric intake, computed as food intake plus alcohol intake, was higher in alcoholics than in control subjects. No statistical differences were found in urinary nitrogen excretion and fecal loss between groups. Patients with alcoholism showed an increased REE over predicted values and a preferential lipid oxidation with respect to controls; these findings could be related to induction of microsomal ethanol oxidizing system and to mitochondrial function adaptation secondary to chronic alcohol abuse. In either case, the effects of such changes in energy metabolism may contribute to alcohol associated hepatic injury.
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PMID:Energy expenditure, substrate oxidation, and body composition in subjects with chronic alcoholism: new findings from metabolic assessment. 930 2

A 16-year-old girl is described with abetalipoproteinaemia who underwent liver transplantation for hepatic cirrhosis. After this procedure her serum lipoprotein profile was corrected; however, fat malabsorption and steatorrhea persisted because the primary defect, a mutant microsomal triglyceride-transfer protein, remains expressed in the intestine.
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PMID:Persistence of the intestinal defect in abetalipoproteinaemia after liver transplantation. 968 20


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