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)

Primary bile acid malabsorption (PBAM) is an idiopathic intestinal disorder associated with congenital diarrhea, steatorrhea, interruption of the enterohepatic circulation of bile acids, and reduced plasma cholesterol levels. The molecular basis of PBAM is unknown, and several conflicting mechanisms have been postulated. In this study, we cloned the human ileal Na+/bile acid cotransporter gene (SLC10A2) and employed single-stranded conformation polymorphism analysis to screen for PBAM-associated mutations. Four polymorphisms were identified and sequenced in a family with congenital PBAM. One allele encoded an A171S missense mutation and a mutated donor splice site for exon 3. The other allele encoded two missense mutations at conserved amino acid positions, L243P and T262M. In transfected COS cells, the L243P, T262M, and double mutant (L243P/T262M) did not affect transporter protein expression or trafficking to the plasma membrane; however, transport of taurocholate and other bile acids was abolished. In contrast, the A171S mutation had no effect on taurocholate uptake. The dysfunctional mutations were not detected in 104 unaffected control subjects, whereas the A171S was present in 28% of that population. These findings establish that SLC10A2 mutations can cause PBAM and underscore the ileal Na+/bile acid cotransporter's role in intestinal reclamation of bile acids.
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PMID:Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). 910 32

Colectomy is performed for inflammatory bowel disease, familial polyposis syndrome and colorectal carcinoma. Surgical procedures are ileostomy with or without pouch, ileorectal anastomosis or ileal pouch-anal anastomosis. One of the major functions of the intact large intestine is to absorb water and electrolytes. After colectomy, as much as 400-1000 ml of nearly isotonic ileostomy fluid may be excreted, resulting in a chronic salt and water depletion. This is compensated for by an activation of the renin-angiotensin-aldosterone system. Reduced urine volumes may cause kidney stones. Both dehydration and renal sodium retention are probably less frequent in patients with ileal pouch-anal anastomosis. Absorption of nutrients in general is not impaired by colectomy. The large intestine salvages energy from malabsorbed organic matter through absorption of the short-chain fatty acids produced in bacterial fermentation. In ileostomy patients, fermentation is negligible, which leads to a significant loss of energy in the ileostomy fluid. Pouches are colonized by a bacterial flora similar to colonic bacteria. In these patients conservation of energy from malabsorbed substrate may be similar to healthy subjects. Resection of ileum and bacterial colonization may lead to malabsorption of vitamin B12 and bile acids. The latter may cause increased incidence of biliary cholesterol stones. Pouchitis is a frequent problem which may be caused by a deficiency of short-chain fatty acids and glutamine in the pouch contents. It is concluded that although the colon is not essential as a digestive organ in man, colectomy results in a number of metabolic changes. The ileal pouch-anal anastomosis may in part substitute for the functions of the large intestine.
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PMID:Metabolic consequences of total colectomy. 914 41

The physicochemical and structural characteristics of several types of carboxymethylcellulose (CMC) and of methylcellulose (MC) were examined in relation to their capacity to modify water and sodium absorption in oral rehydration solutions (ORS) at various concentrations, using a jejunal perfusion procedure in rats. Comparison of intrinsic low-viscosity CMC of various degrees of substitution (DS) revealed that net water absorption increased as the DS was augmented. A stimulatory effect on sodium absorption occurred only at a low (2.5 g/l) CMC concentration. With products of medium DS, stimulation of net water and sodium absorption was observed only with low-viscosity CMC at 2.5 g/l, but not at 5.0 g/l. In perfusions with CMC of medium and high DS there was a reduction of water and sodium absorption, ultimately resulting in net sodium secretion with 5.0 g/l high-DS CMC. MC perfused at 5.0 or 10.0 g/l reduced net water absorption and reversed sodium transport from absorptive to secretory status. These results show that while low-viscosity-grade, low-DS CMC in low concentrations may facilitate solute uptake and concurrent water absorption from ORS by the jejunum, high intrinsic viscosity and possible chemical interaction of solutes with the modified celluloses tend to block water uptake and produce fluid stasis and electrolyte secretion. Thus, the data suggest that only certain types of CMC may be proabsorptive when added to ORS, while high-viscosity and high-DS CMC or MC induce electrolyte malabsorption and eventual catharsis.
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PMID:Cellulose derivatives and intestinal absorption of water and electrolytes: potential role in oral rehydration solutions. 920 64

Plasma chemistry and haematological studies were conducted on chickens with coccidiosis. Male White Leghorn chickens, of two weeks old, were inoculated with 5 x 10(4) Eimeria tenella sporulated oocysts or with 1 x 10(6) E acervulina sporulated oocysts. Blood samples were taken four, seven and 11 days after inoculation. A wet chemistry system was applied to measure the plasma activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyltransferase, creatine kinase, amylase and lactate dehydrogenase and the concentrations of creatine, total bilirubin, urate, total cholesterol, total protein, albumin, glucose and triglycerides. A dry chemistry system was applied to measure sodium, potassium, chloride and calcium. The number of red blood cells and packed cell volume were determined by a micro cell counter and blood pH was measured with a blood gas analyser. The erythrocyte count, packed cell volume, sodium and chloride levels in the chickens infected with E tenella were significantly (P < 0.05) lower than those of the uninfected controls. The significant decrease in blood pH of the chickens infected with E acervulina suggests malabsorption associated with duodenal lesions induced by the infection.
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PMID:Evaluation of plasma chemistry and haematological studies on chickens infected with Eimeria tenella and E acervulina. 925 31

Human immunodeficiency virus (HIV)-infected patients display severe impairments of gastrointestinal functions, including diarrhea and malabsorption, even in the absence of opportunistic infections. Since HIV-1 proteins and nucleic acids have been detected in several cell types of the intestinal mucosa, it has been postulated that HIV-1 itself could alter enterocytic functions. In the present study, we analyzed the effect of HIV-1 on the differentiation process of the epithelial intestinal cell clone HT-29-D4, which mimics the maturation of enterocytes along the crypt-villus axis of the small intestine. We found that HIV-1 infection impairs cellular differentiation (i) by affecting the barrier function of the epithelium, as evidenced by a decrease in the transepithelial electrical resistance, and (ii) by inhibiting the activity of one major glucose absorption function, i.e., sodium/glucose cotransport. At the morphological level, HIV-1 infection of HT-29-D4 cells was associated with the formation of lumina, which are representative of a defect in cellular organization. These morphofunctional perturbations induced by HIV-1 could be mimicked by nocodazole, a microtubule-disrupting agent. Correspondingly, HIV-1 exposure of HT-29-D4 cells evoked a massive disruption of microtubules, as revealed by alpha-tubulin indirect immunofluorescence staining. A similar effect was observed after incubation of the cells with either recombinant gp120 or a monoclonal antibody against galactosylceramide (GalCer), the intestinal receptor for HIV-1 gp120, suggesting that the effect of HIV-1 was mediated by the binding of gp120 to GalCer. Based on these data, we propose that HIV-1 may selectively alter enterocytic functions through a direct effect on the intracellular architecture of the cells. In contrast with previous theories for HIV-1 enteropathy, our data support the concept that HIV-1 may perturb intestinal functions without necessarily infecting intestinal epithelial cells.
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PMID:Direct effect of type 1 human immunodeficiency virus (HIV-1) on intestinal epithelial cell differentiation: relationship to HIV-1 enteropathy. 940 May 96

The enterohepatic circulation of bile acids is maintained by a series of membrane transport proteins. Recent studies of the cloned sodium bile acid cotransporters have provided new insights into their tissue expression, regulation, and their relationship to cholesterol homeostasis and human diseases such as primary bile acid malabsorption.
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PMID:New insights into bile acid transport. 964 5

Intestinal adaptation is a complex physiologic process that is not completely understood. Intravenous short-chain fatty acids (SCFAs) enhance intestinal adaptation after 80% enterectomy in rats. The purpose of this study was to examine rapid responses to SCFA-supplemented total parenteral nutrition (TPN) in the normal small intestine. After jugular catheterization, 31 Sprague-Dawley rats (weighing 258 +/- 3 g) were randomly assigned to receive standard TPN or an isoenergetic, isonitrogenous TPN solution supplemented with SCFAs (TPN+SCFA). Intestinal samples were obtained after 24 or 72 h of nutrient infusion. TPN+SCFA for 24 h increased (P < 0.05) the ileal RNA concentration (microg RNA/mg ileum) whereas TPN+SCFA for 72 h increased (P < 0.05) the ileal DNA concentration (microg DNA/mg ileum) and decreased (P < 0.05) the ileal protein concentration (microg protein/mg ileum). Ileal proglucagon mRNA abundance was elevated (P < 0.05) after 24 h of TPN+SCFA infusion and returned to levels seen with control TPN by 72 h. Glucose transporter 2 (GLUT2) mRNA was significantly higher (P < 0.05) in the TPN+SCFA groups at both time points when compared with control TPN groups. Ileal GLUT2 protein abundance in the 72-h TPN+SCFA group was significantly higher (P < 0.05) than that of all other groups. Sodium-glucose cotransporter (SGLT-1) mRNA and protein abundance and uptake of D-fructose and D-glucose did not differ between groups. Jejunal uptake of L-glucose and lauric acid was significantly higher (P < 0.05) after 72 h of TPN+SCFA than after 24 h, whereas the 24- and 72-h TPN groups did not differ. In summary, SCFAs led to rapid changes in ileal proglucagon and glucose transporter expression in rats receiving TPN and provide insights into therapeutic management of individuals with short bowel syndrome or intestinal malabsorption syndromes.
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PMID:Short-chain fatty acid-supplemented total parenteral nutrition alters intestinal structure, glucose transporter 2 (GLUT2) mRNA and protein, and proglucagon mRNA abundance in normal rats. 966 5

Exposure of the ileum to nutrients markedly inhibits several upper gastrointestinal functions. Hormonal peptides of the ileal wall, i.e. peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and neurotensin (NT), are thought to play a role in this negative feedback mechanism. The present study was conducted to comparatively assess the secretion of PYY, GLP-1, and NT upon luminal infusion of a variety of individual luminal factors in the isolated vascularly perfused rat ileum preparation. PYY, GLP-1, and NT were measured in the portal effluent with specific RIAs. Glucose (250 mM) induced a pronounced release of the three peptides, whereas a physiological concentration of 5 mM did not induce peptide secretion. Peptone (5%, wt/vol) evoked a sustained release of PYY, GLP-1, and NT. Only NT secretion was increased upon luminal administration of 100 mM sodium oleate. Short chain fatty acids (20 mM) evoked an early and transient release of the three peptides. In contrast, taurocholate (20 mM) induced a sustained release of PYY, GLP-1, and NT, but the threshold concentration for peptide release was lower for NT than for PYY or GLP-1. Cellulose or pectin (0.5%, wt/vol) did not modify peptide secretion. In conclusion, glucose and peptone are potent stimulants of PYY, GLP-1, and NT release. Only NT is released upon oleic acid stimulation. Finally, taurocholate is a potent stimulant of the release of the three peptides. Overall, PYY, GLP-1, and NT may participate cooperatively in the ileal brake. As relatively high concentrations of the various stimulants were required to elicit peptide release, it seems likely that this mechanism operates in cases of maldigestion or malabsorption.
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PMID:Peptide YY, glucagon-like peptide-1, and neurotensin responses to luminal factors in the isolated vascularly perfused rat ileum. 972 30

Intestinal bile acid absorption is a fundamental step in the enterohepatic circulation and metabolism of these endogenous compounds. The physiology of the active, sodium coupled transport system for bile acids in the terminal ileum has been extensively studied and characterized. Structure-activity studies have elucidated the requirements for the ileal transport system, and studies with photolabile bile acid derivatives identified the putative ileal bile acid transport proteins. Characterization of the functional sites of the transport system elucidated some of the possible mechanisms which allow the interaction of bile acids and sodium ions with the ileal transporter. Considerable progress has been made during recent years, after the ileal apical and cytosolic bile acid transport proteins have been cloned and characterized. The role of point mutations in bile acid malabsorption has been studied, and the knowledge of the amino acid sequence of the transport proteins will be of help in the investigation of the transport mechanisms.
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PMID:New insights in the physiology and molecular basis of the intestinal bile acid absorption. 978 45

In the rapidly increasing elderly population, diarrhoea as a result of drug therapy is an important consideration. The elderly consume a disproportionately large number of drugs for multiple acute and chronic diseases. Drugs can compromise both immune and nonimmune responses. Aging decreases the quality and proportion of T cells which in turn reduces the production of secretory IgA, the primary immune response of the gut. Acid production in the stomach decreases with increasing age and this compromise its vital 'self-sterilising' function, thus increasing the risk of diarrhoea due to viral, bacterial and protozoal pathogens. Other nonimmune defence mechanisms include the motility of the small intestine and the host-protective commensal bacteria of the colon. Drug induced hypomotility may result in bacterial overgrowth, deconjugation of bile salts and diarrhoea. Less commonly, diarrhoea may occur due to hypermotility because of a cholinergic-like syndrome. In the colon the host-protective commensal bacteria provide a powerful defence against pathogens. Disruption of this commensal population by antibiotic therapy may result in Clostridium difficile supra-infection which causes diarrhoea through toxin production. This is especially important in the elderly patient on chemotherapy for malignancy and those with multiple diseases. The organism responds to vancomycin, metronidazole and bacitracin. Metronidazole is the suggested drug of choice, with vancomycin reserved for relapses. Drugs also cause diarrhoea by interfering with normal physiological processes. Drugs impair fluid absorption by activating adenylate cyclase within the small intestinal enterocyte which increases the level of cyclic AMP. This causes active secretion of Cl- and HCO3-, passive efflux of Na+, K+ and water and inhibition of Na+ and Cl- into the enterocyte. Examples of these drugs (secretagogues) are bisacodyl, misoprostol and chenodeoxycholic acid (used to dissolve cholesterol gallstones). Drugs may also affect a second mechanism that regulates water and electrolyte transport, the Na+, K+ exchange pump. The energy for this pump is provided by the ATPase mediated breakdown of ATP. ATPase may be inhibited by digoxin, auranofin, colchicine and olsalazine. A number of drugs cause osmotic diarrhoea including antacids containing magnesium trisilicate or hydroxide. Lactulose is being used increasingly in compensated liver disease to increase protein tolerance and prevent hepatic encephalopathy. Sorbitol, an osmotic laxative agent also used in some liquid pharmaceutical preparations, induces diarrhoea by virtue of its osmotic potential. Another mechanism by which drugs cause diarrhoea is by mucosal damage of the small and large bowel. In the small intestine mucosal damage causes diarrhoea and fat malabsorption, as may occur with neomycin and colchicine. In the colon, for example, gold salts and penicillamine cause colitis of varying severity. Though the causes of diarrhoea are diverse, a drug-associated aetiology should always be considered and actively sought and addressed to prevent the complications of dehydration, electrolyte imbalance and undernutrition.
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PMID:Mechanisms of drug-induced diarrhoea in the elderly. 978 28


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