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

Increased concentrations of reactive oxygen species in children with depleted antioxidant defences have been implicated in a cycle of malnutrition, malabsorption, and infection leading to protracted diarrhoea. A rat model of chronic vitamin E deficiency has been used to study the effects of antioxidant depletion on jejunal structure and function in vitro. Basal intestinal short circuit current (Isc), a measure of net electrogenic ion movement across the intestinal epithelium, was greater in chronically vitamin E deficient jejuna than controls, as was the electrogenic secretory response to aminophylline and Escherichia coli STa but not to bethanechol. The galactose stimulated current was also greater in vitamin E deficient jejuna. Indices of lipid peroxidation (concentrations of thiobarbituric acid reactive substances and malondialdehyde) were increased in the vitamin E deficient small bowel. Small intestinal brush border membranes from vitamin E deficient animals displayed changes in both static and dynamic components of membrane fluidity measured by steady state fluorescence polarography. The results of these studies support the hypothesis that oxidative stress in subjects with compromised antioxidant defences results in small intestinal hypersecretion, which could predispose to or perpetuate protracted diarrhoea.
 ...
PMID:Lipid peroxidation and electrogenic ion transport in the jejunum of the vitamin E deficient rat. 830 46

Resection of distal small intestine causes calcium malabsorption in humans and in a rat model of 50% distal resection. We tested the hypothesis that this calcium malabsorption is caused in the rat model by a brush border defect. We compared brush border membrane vesicles from the proximal small intestine of control (transection and anastomosis at mid-small intestine) with distally resected rats. Mucosal protein was 25% greater in the resected group and the vesicles were enriched 37-fold in sucrase activity when compared with homogenate. Kinetic constants Vmax (maximal initial rate of saturable calcium uptake at infinite concentration), kT (calcium concentration for saturable calcium uptake rate at half Vmax), and KD (rate constant for nonsaturable calcium uptake per unit concentration) were slightly but not significantly greater in the resected as compared with the transected group, ruling out the brush border as the cause for decreased transmucosal calcium transport.
 ...
PMID:Brush border calcium uptake in short-bowel syndrome in rats. 841 65

Cotransporters harness ion gradients to drive 'active' transport of substrates into cells, for example, the Na+/glucose cotransporter (SGLT1) couples sugar transport to Na+ gradients across the intestinal brush border. Glucose-Galactose Malabsorption (GGM) is caused by a defect in SGLT1. The phenotype is neonatal onset of diarrhea that results in death unless these sugars are removed from the diet. Previously we showed that two sisters with GGM had a missense mutation in the SGLT1 gene. The gene has now been screened in 30 new patients, and a heterologous expression system has been used to link the mutations to the phenotype.
 ...
PMID:Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption. 856 65

Normal intestinal absorption of nutrients requires efficient luminal mixing to deliver solute to the brush border. Lacking such mixing, the buildup of thick unstirred layers over the mucosa markedly retards absorption of rapidly transported compounds. Using a technique based on the kinetics of maltose hydrolysis, we measured the unstirred layer thickness of the jejunum of normal subjects and patients with celiac disease, as well as that of the normal rat. The jejunum of humans and rats was perfused with varying maltose concentrations, and the apparent Michaelis constant (Km) and maximal velocity (Vmax) of maltose hydrolysis were determined from double-reciprocal plots. The true Km of intestinal maltase was determined on mucosal biopsies. Unstirred layer thickness was calculated from the in vivo Vmax and apparent Km and the in vitro Km of maltase. The average unstirred layer thickness of 11 celiac patients (170 micron) was seven times greater than that of 3 controls (25 micron). The unstirred layer of each celiac exceeded that of the controls. A variety of factors could account for the less efficient luminal stirring observed in celiacs. Although speculative, villous contractility could be an important stirring mechanism that would be absent in celiacs with villous atrophy. This speculation was supported by the finding of a relatively thick unstirred layer (mean: 106 micron) in rats, an animal that lacks villous contractility. Because any increase in unstirred layer slows transport of rapidly absorbed compounds, poor stirring appears to represent a previously unrecognized defect that could contribute to malabsorption in celiac disease and, perhaps, in other intestinal disorders.
 ...
PMID:Measurements of the jejunal unstirred layer in normal subjects and patients with celiac disease. 863 15

The aetiology of weight loss in patients with Parkinson's disease is likely to be multifactorial. We studied 15 patients with Parkinson's disease and 15 age- and sex-matched controls and looked for evidence of malabsorption due to small bowel bacterial overgrowth or alteration of intestinal permeability. There was a marked increase in orocaecal transit time in the patients with Parkinson's disease, although lactulose hydrogen breath testing did not show evidence of small bowel bacterial contamination. Intestinal permeability measured by the differential sugar absorption test was also deranged. There was reduced absorption of mannitol in patients with Parkinson's disease while lactulose absorption was similar in both groups, suggesting decreased non-mediated uptake across the enterocyte brush border membrane in patients with Parkinson's disease.
 ...
PMID:Intestinal permeability and orocaecal transit time in elderly patients with Parkinson's disease. 949 97

The therapeutic effect of acarbose is generally attributed to inhibition of amylase and brush border glucosidases and consequent impaired digestion and absorption of carbohydrates. We have investigated the possibility that acarbose may also influence the rate of gastric emptying by comparing plasma glucose and gastrointestinal hormone responses to an oral sucrose load with and without acarbose in 11 healthy subjects. Gastric emptying was assessed indirectly by measuring circulating paracetamol concentrations following administration of paracetamol along with the sucrose load. Peak plasma glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) responses were reduced when sucrose was given with acarbose. There was a significant reduction in post-sucrose paracetamol levels with acarbose suggestive of a significant delay in gastric emptying. The failure of acarbose to induce change in circulating paracetamol concentrations until after 60 min is indicative of a delay in gastric emptying rather than an osmotic malabsorption. The exaggerated and sustained release of glucagon-like peptide-1 (7-36)amide (GLP-1) seen when sucrose was given with acarbose may play a part in the inhibition of gastric emptying. This study indicates that a significant delay in gastric emptying may be an added mechanism contributing to the therapeutic effect of acarbose.
 ...
PMID:Delayed gastric emptying occurs following acarbose administration and is a further mechanism for its anti-hyperglycaemic effect. 950 11

Glucose Galactose Malabsorption is a genetic disorder caused by a defect in glucose and galactose transport across the intestinal brush border. Normally, lactose in milk is broken down into glucose and galactose by lactase, an ectoenzyme on the brush border, and the hexoses are transported into the cell by the Na+-glucose cotransporter SGLT1. The mutations causing the defect in sugar transport have been identified in patients from 33 kindreds, and functional studies have established how these mutations cause the disease.
 ...
PMID:I. Glucose galactose malabsorption. 981 14

Intestinal colonization with the protozoan Giardia causes diffuse brush border microvillous alterations and disaccharidase deficiencies, which in turn are responsible for intestinal malabsorption and maldigestion. The role of T cells and/or cytokines in the pathogenesis of Giardia-induced microvillous injury remains unclear. The aim of this study was to assess the role of T cells and interleukin-6 (IL-6) in the brush border pathophysiology of acute murine giardiasis in vivo. Athymic nude (nu(-)/nu(-)) CD-1 mice and isogenic immunocompetent (nu(+)/nu(+)) CD-1 mice (4 weeks old) received an axenic Giardia muris trophozoite inoculum or vehicle (control) via orogastric gavage. Weight gain and food intake were assessed daily. On day 6, segments of jejunum were assessed for parasite load, brush border ultrastructure, IL-6 content, maltase and sucrase activities, villus-crypt architecture, and intraepithelial lymphocyte (IEL) infiltration. Despite similar parasitic loads on day 6, infected immunocompetent animals, but not infected nude mice, showed a diffuse loss of brush border microvillous surface area, which was correlated with a significant reduction in maltase and sucrase activities and a decrease in jejunal IL-6 concentration. In both athymic control and infected mice, jejunal brush border surface area and disaccharidases were high, but levels of tissue IL-6 were low and comparable to the concentration measured in immunocompetent infected animals. In both immunocompetent and nude mice, infection caused a small but significant increase in the numbers of IELs. These findings suggest that the enterocyte brush border injury and malfunction seen in giardiasis is, at least in part, mediated by thymus-derived T lymphocytes and that suppressed jejunal IL-6 does not necessarily accompany microvillous shortening.
 ...
PMID:Jejunal brush border microvillous alterations in Giardia muris-infected mice: role of T lymphocytes and interleukin-6. 1081 92

Carcinogenic and other toxic manifestations of areca/betel nut extracts on the buccal cavity and upper digestive tract are well documented. The present study deals with in vivo and in situ effects of aqueous and alcoholic extracts of areca nut on rat intestinal epithelial cell membrane. In vivo daily oral administration by gastric intubation for 1p w produced significant declines in brush border membrane alkaline phosphatase, Ca2+-Mg2+-ATPase, and the digestive enzyme sucrase. The decline in activities were more prominent after 4-w exposures. Instant short term in situ exposure to aqueous extract produced higher enzyme activities, indicating the initial activation of active sites by areca nut extract constituent(s). Significant declines in brush border membrane constituents (total hexose, sialic acid and cholesterol) were also evident following continuous exposures to areca nut extracts. These findings suggest that prolonged chewing of areca nut causes significant alterations in intestinal epithelial cell lining functions and could lead to malabsorption of nutrients.
 ...
PMID:Effect of betel/areca nut (Areca catechu) extracts on intestinal epithelial cell lining. 1100 13

Some interesting advances in mechanisms and regulation of nutrient absorption were reported last year. Further evidence was obtained that the rate-limiting step in triacylglycerol absorption, especially with large doses of lipid, is transport of prechylomicrons from the endoplasmic reticulum to the Golgi apparatus. Targeted disruption of the adenosine triphosphate-binding cassette transporter in mice produced changes similar to human Tangier disease and suggested that this mouse may be a model for studying intestinal high-density lipoprotein assembly and secretion. A new mechanism for carbohydrate malabsorption was discovered: in sucrase-isomaltase deficiency, the enzyme fails to anchor in the brush border membrane and so is secreted into the lumen, where it is ineffective. Glycosylating insulin at B1 phenylalanine permitted it to bind to the brush border membrane and greatly enhanced its hypoglycemic activity when given orally. CaCo-2 cells and normal human enterocytes were shown to have two variants of the human sodium-dependent vitamin C transporter, hSVCT1; one is active and the other is an inactive splice variant. In rats, the divalent metal ion transporter, DMT1, appeared to be important for regulation of both absorption of iron and its movement into the liver.
 ...
PMID:Nutrient absorption. 1122 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>