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 properties of cholylsarcosine (the synthetic N-acyl conjugate of cholic acid with sarcosine [N-methylglycine]) were examined to determine its suitability as a bile acid replacement agent for conditions of bile acid deficiency in the small intestine, which causes fat malabsorption. Previous studies in rodents had shown that the compound was well transported by the liver and ileum and underwent neither deconjugation nor dehydroxylation during enterohepatic cycling. By 1H-nuclear magnetic resonance, cholylsarcosine was found to exist in dilute aqueous solution as an almost equimolar mixture of two geometric isomers--cis and trans (around the amide bond)--in contrast to cholylglycine, which was present entirely in the trans form. The critical micellization concentration was 11 mmol/liter, similar to that of cholylglycine (10 mmol/liter). By nonaqueous titrimetry, the pKa' of cholylsarcosine was 3.7, only slightly lower than that of cholylglycine (3.9). Cholylsarcosine was poorly soluble below pH 3.7, but highly soluble above pH 4. In vitro, cholylsarcosine behaved as cholylglycine with respect to promoting lipolysis by lipase/colipase. There was little difference between cholylsarcosine and cholylglycine in their solubilization of an equimolar mixture of oleic acid, oleate, and monoolein (designed to simulate digestive products of triglyceride) or in their solubilization of monooleyl-glycerol alone. When a [3H]triolein emulsion with either cholylsarcosine or cholyltaurine was infused intraduodenally in biliary fistula rats, recovery of 3H in lymph was 52 +/- 10% (mean +/- SD) for cholylsarcosine and 52 +/- 11% for cholyltaurine. When perfused into the colon of the anesthetized rabbit, cholylsarcosine (5 mmol/liter) did not influence water absorption or permeability to erythritol, in contrast to chenodeoxycholate, which induced vigorous water secretion and caused erythritol loss. We conclude that cholylsarcosine possesses the physicochemical and physiological properties required for a suitable bile acid replacement in deficiency states.
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PMID:Physicochemical and physiological properties of cholylsarcosine. A potential replacement detergent for bile acid deficiency states in the small intestine. 137 Nov 23

The effects of various structured triglycerides containing medium-chain (caprylic or capric acids) and long-chain (linoleic acid) fatty acids on fatty acid and cholesterol absorption were studied in lymph-cannulated rats. A considerable portion of capric and caprylic acid was absorbed through the lymph duct, although to a lesser extent than was linoleic acid. Capric and linoleic acid located at the 2-position of 2-decanoyl-1,3-dilinoleoyl-glycerol (18:2/10:0/18:2) and 2-linoleoyl-1,3-didecanoyl-glycerol (10:0/18:2/10:0), respectively, tended to be absorbed more efficiently than those located at the 1- and 3-position or those from tricaprin (10:0/10:0/10:0) or trilinolein (18:2/18:2/18:2). A similar trend was observed when the medium-chain fatty acid was caprylic acid instead of capric acid. Caprylic acid absorption from 2-octanoyl-1,3-dilinoleoyl-glycerol (18:2/8:0/18:2) was significantly greater (p less than 0.05) than from 2-linoleoyl-1,3-dioctanoyl-glycerol (8:0/18:2/8:0) or tricaprylin (8:0/8:0/8:0). Preferential absorption of caprylic and linoleic acid was not observed when the 1 to 2 and the 2 to 1 mixtures of 8:0/8:0/8:0 and 18:2/18:2/18:2, respectively, were administered. The structured lipids did not affect the lymphatic absorption of cholesterol. The results suggest that structured triglycerides composed of medium-chain fatty acids and linoleic acid may be more useful for the treatment of lipid malabsorption than are mixtures of medium-chain triglyceride (MCT) and long-chain triglyceride (LCT).
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PMID:Lymphatic absorption of structured glycerolipids containing medium-chain fatty acids and linoleic acid, and their effect on cholesterol absorption in rats. 189 84

Diarrhea and weight loss may accompany the acquired immunodeficiency syndrome. We studied 30 patients with the syndrome, 20 of whom had diarrhea and weight loss and 10 of whom did not. Patients with identifiable enteric infections or small intestinal Kaposi's sarcoma were excluded. Malabsorption was common in the patients with diarrhea and weight loss, as shown by abnormal D-xylose and 14C-glycerol-tripalmitin absorption tests. In these patients, duodenal biopsy specimens showed a histiocytic infiltrate containing numerous acid-fast organisms in 5 and a mild-moderate chronic inflammation in 13. In asymptomatic patients, duodenal biopsy specimens were normal in 6 and showed chronic inflammation in 4. These results suggest that malabsorption is common in patients with the acquired immunodeficiency syndrome with chronic diarrhea and may contribute to their weight loss.
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PMID:Malabsorption and mucosal abnormalities of the small intestine in the acquired immunodeficiency syndrome. 398 13

A tritium-labeled glycerol triether was tested as a nonabsorbable oil-phase marker in studies of fat absorption in normal rats and in rats with steatorrhea induced by various doses of cholestyramine. Animals were fed a test meal containing (3)H-labeled triether and (14)C-labeled trilinolein. Fat absorption was estimated in the following three ways: (a) by isotope ratios (the change in (3)H/(14)C in the test meal and in feces); (b) by isotope recovery (the total fecal excretion of (14)C radioactivity); and (c) by chemical recovery (the total fecal fat excretion). Absorption calculated from isotope ratios agreed well with that calculated from isotope recovery over a range of fat absorption of 50-100%, thus validating the use of this lipid marker under these conditions of fat malabsorption. Absorption calculated from chemical recovery was consistently poorer than that calculated from isotope ratios or isotope recovery, thus suggesting that cholestyramine increased the excretion of nondietary (endogenous) fat. Triether may be of value for studying the absorption of compounds present predominantly in the oil phase during digestion and may have significant advantages over other proposed lipid markers.
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PMID:Use of 3H-labeled triether, a nonabsorbable oil-phase marker, to estimate fat absorption in rats with cholestyramine-induced steatorrhea. 544 Dec 48

In order to study arterial concentrations and splanchnic exchange of substrates and hormones in patients with chronic inflammatory bowel disease three patients with Crohn's disease and four with ulcerative colitis were studied using the hepatic venous catheter technique. Systemic turnover and regional exchange of free fatty acid were evaluated using intravenous infusion of 14C-labelled oleic acid. All measurements were made in the postabsorptive, overnight fasted state. Arterial glucose concentrations were 10% lower in the patients but net splanchnic glucose output was similar in patients and controls. Glucose precursor uptake (lactate, pyruvate, and glycerol), however, was increased two to five fold in the patients. Arterial amino acid concentrations were generally reduced but net splanchnic amino acid uptake was the same in patients and controls. Arterial concentrations of free fatty acid and oleic acid as well as systemic and fractional turnover were similar in patients and controls. The patients' splanchnic uptake of oleic acid was increased more than three fold in comparison with controls. Splanchnic release of oleic acid was also augmented in the patients. Both arterial concentrations and splanchnic production of ketone bodies were raised in the patients. The proportion of splanchnic free fatty acid uptake which could be accounted for by ketone body production was significantly greater in the patients (37 +/- 4%) than the controls (20 +/- 5%, p less than 0.025). Estimated hepatic blood flow was 55% greater (p less than 0.01) in the patients as compared with the controls (1930 +/- 150 vs 1240 +/- 70 ml/min), while splanchnic oxygen uptake was similar in the two groups. From these findings it is concluded that patients with chronic inflammatory bowel disease show (1) markedly increased hepatic blood flow, reflecting an inflammatory hyperaemia in the splanchnic region, (2) a normal net splanchnic glucose output, (3) accelerated hepatic gluconeogenesis as well as ketogenesis, probably as a consequence of the altered hormonal milieau, and (4) low concentrations of most amino acids possibly because of protein malabsorption. These findings underscore the importance of adequate protein and carbohydrate administration to this patient group.
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PMID:Splanchnic exchange of glucose, amino acids and free fatty acids in patients with chronic inflammatory bowel disease. 664 79

Three tests were evaluated as screening procedures for fat malabsorption--namely, measurement of serum optical density, serum triglyceride concentration, and 14CO2 breath excretion after the administration of a 60 g fat meal containing 10 muCi glycerol tri[1-14C]oleate. The results of these tests were compared with fat excreted in a three-day faecal collection after adjustment for completeness of collection as assessed by using non-absorbable radio-opaque markers. Fifty-two patients with various symptoms and eight normal subjects were studied. The maximum increase in serum optical density or triglyceride concentration above the fasting value discriminated poorly between subjects with normal and increased adjusted faecal fat excretion. In contrast, seven- or eight-hour cumulative 14CO2 breath excretion provided good discrimination with only four (7%) false-positive and no false-negative results. The simplicity and convenience of breath analysis make it an attractive alternative to analysis of faecal fat excretion in screening for fat malabsorption.
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PMID:Comparison of simple screening tests for fat malabsorption. 678 33

A new test of intraluminal fat digestive activity is proposed for which a mixed triglyceride, 1,3-dioleyl-2-14C-decanoyl glycerol, was used. 29 normal subjects, 14 patients with proven chronic pancreatitis, 10 pancreatectomy, 12 villus atrophy and 8 bile acid-deficient patients were studied. The mean 14CO2 excretion in breath, expressed as the 10th-hour cumulative percentage of the administered dose, was 68.3% in the normal subjects, and only 32.9% in patients with pancreatic disease. There was almost no overlap between the normal subjects and the patients with proven organic disease. The test also allowed the detection of functional pancreatic insufficiency, due to impaired pancreatic stimulation in case of gluten enteropathy and severe malabsorption.
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PMID:A mixed-triglyceride breath test for intraluminal fat digestive activity. 679 47

Children with cystic fibrosis have variable degrees of exocrine pancreatic insufficiency which, if untreated, is the main cause of fat malabsorption. The impact of pancreatic enzyme supplementation on fat digestion was measured in 41 children with cystic fibrosis, 11 healthy controls, and five children with mucosal diseases by a non-invasive test of intraluminal lipolysis using 13carbon (13C) labelled mixed triglyceride (1,3-distearyl, 2[13C] octanoyl glycerol). The children with cystic fibrosis without pancreatic supplements had a median (range) 13C cumulative percentage dose recovered over six hours (cPDR) of 3.1% (0-31.7), the controls 31.0% (21.8-41.1), and the subjects with mucosal disease 27.8% (19.7-32.5). In 23 subjects with cystic fibrosis the usual dose of pancreatic enzyme supplements increased the cPDR to a median of 23.9% (0-45.6), and twice the usual dose of enteric coated microspheres increased the cPDR to 31.1% (11.1-47.8). There was no significant difference between the median cPDR of normal controls and children with mucosal disease, but there was a highly significant difference between these groups and children with untreated cystic fibrosis. Thirteen children with cystic fibrosis had no 13C recovery in their breath without enzymes and 10 showed marked increases with regular enzymes. In eight children doubling the dose of enzymes caused no or minimal improvement. The mixed triglyceride breath test offers a simple, non-invasive way of assessing the need for pancreatic enzyme supplementation in children with cystic fibrosis and could be used to optimise treatment.
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PMID:13Carbon mixed triglyceride breath test and pancreatic enzyme supplementation in cystic fibrosis. 916 30

Laboratory assessment of pancreatic function is unpleasant for the patient and time-consuming for the investigator since it requires duodenal intubation and measurement of maximal pancreatic enzyme output by means of perfusion techniques. Non-invasive indirect tests such as bentiromide test, pancreolauryl test and faecal fat measurement have been introduced in clinical practice but their results depend on the collaboration of the patient in collecting urine or stool. Moreover, faecal fat reflects fat malabsorption but it is neither sensitive nor specific to evaluate exocrine pancreatic function. With the aim to determine whether steatorrhea is due to pancreatic insufficiency, several 14C- (or 13C) breath tests have been developed in which triolein, trioctanoin, tripalmitin, and cholesteryl-octanoate are used as marker substances. In 1989, G. Vantrappen and its group in Leuven developed a breath test in which a new substrate was used: the [1,3-distearyl, 2[carboxyl-13C]octanoyl glycerol] or 13C-"mixed"-triglyceride (MT). The "mixed triglyceride breath test" (MTBT) was shown to be an excellent test of exocrine pancreatic insufficiency when compared with the maximal lipase output after CCK-pancreozymin stimulation. Aim of this paper is to review the methodology of the MTBT and its actual and future applications in clinical practice.
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PMID:"Mixed" triglyceride breath test: methodological problems and clinical applications. 1042 Sep 46

Carboxyl ester lipase (bile salt-stimulated lipase) is a pancreatic enzyme capable of hydrolyzing esters of cholesterol and fat-soluble vitamins. It also efficiently digests triglycerides (TG) into free fatty acids and glycerol and is abundant in the milk of humans and several other species. We used the mouse as a model to test the hypothesis that milk-derived carboxyl ester lipase (CEL) digests milk TG and that without its activity milk lipids and their digestion intermediates can disrupt the intestinal epithelium of neonates. CEL protein and enzymatic activity were shown to be abundant in mouse milk. After 24-h administration of the CEL-specific inhibitor, WAY-121,751-5, the small intestines of treated and control neonates were analyzed histologically for signs of fat malabsorption and injury to their villus epithelium. In vehicle-fed controls, TG were digested and absorbed in the duodenum and jejunum, whereas, in inhibitor-fed littermates, large intracellular neutral lipid droplets accumulated in enterocytes of the ileum, resulting in damage to the villus epithelium. Similar results were observed in neonates nursed by CEL knockout females compared with heterozygous controls. The results suggest that lack of CEL activity causes incomplete digestion of milk fat and lipid accumulation by enterocytes in the ileum of neonatal mice.
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PMID:Carboxyl ester lipase activity in milk prevents fat-derived intestinal injury in neonatal mice. 1048 91


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