Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.26 (invertase)
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Metronidazole (Flagyl), an antibiotic commonly used in treating intestinal infections, when administered orally at a dose level of 100 mg/kg body weight daily for 7 days to rats brought about a significant elevation of the uptake of end-product nutrients like D-glucose, L-alanine, L-aspartic acid and L-leucine in the intestinal segments. Brush border membrane-bound hydrolytic enzymes, i.e. sucrase, lactase, maltase, alkaline phosphatase and leucine aminopeptidase levels, were also elevated. Substrate kinetic analysis of the uptake of nutrients as well as the enzymes indicated that the drug increased the maximum of apparent initial velocity, while the substrate affinity constants did not change. Studies of the temperature-dependent parameters of the nutrient uptake and the enzyme activity revealed that metronidazole did not induce any shift in the transition temperature (T(o)) for the uptake but the energy of activation (Ea) was reduced in all the cases except those of maltase and leucine aminopeptidase, which registered an increase in Ea and a marginal shift in T(o), respectively. A significant elevation was seen in the levels of membrane cholesterol, phospholipid, ganglioside and plasmalogen in metronidazole-treated animals, while triglycerides and the non-esterified fatty acids remained unaffected. The effects produced by metronidazole treatment persisted in the animals, which were allowed a recovery period of 7 days after the drug regimen.
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PMID:Effect of the antiprotozoal agent metronidazole (Flagyl) on absorptive and digestive functions of the rat intestine. 147 60

Paired xenografts of near-term fetal rabbit jejunum were subcutaneously implanted in the backs of athymic nude (nu/nu) mice. At 3 to 4 weeks post-implantation, the grafts had histologic, ultrastructural, and biochemical (lactase, sucrase, alkaline phosphatase, leucine aminopeptidase) parameters comparable to age-matched control rabbits. Four weeks post-transplantation the xenografts were intraluminally inoculated with various strains of lapine attaching and effacing E. coli or group A rotavirus. Infection with 2 strains of E. coli resulted in typical light microscopic and ultrastructural lesions of attachment and effacement. Immunohistochemical analysis of rotavirus-infected xenografts demonstrated rotavirus antigen within enterocytes. These lesions are comparable to those in conventional rabbits. Intestinal xenografts are a novel, highly controlled, and reproducible model which may have unique applications in the study of enteric diseases. The model provides anatomically and biochemically correct intestinal mucosal epithelium uncomplicated by variables such as enteric flora, host immune response, gastric, hepatic, and pancreatic secretions and is susceptible to infection by specific enteropathogens. Xenografts, therefore, may be a viable alternative in certain investigations where whole animals, ligated intestinal loops, organ cultures, or cell cultures might otherwise be chosen.
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PMID:Development, characterization, and utilization of an intestinal xenograft model for infectious disease research. 175 15

Oral administration of the antiulcerogenic drug, cimetidine, was studied on kidney-bound hydrolytic enzymes at three different dose levels (30 mg, 100 mg, and 2000 mg/kg body weight) and for single administration for 2 and 24 h, and daily administration for 15 days in mice. It significantly inhibited Na+, K(+)-ATPase, Mg(2+)-ATPase, and Ca2+, Mg(2+)-ATPase in the isolated basolateral membrane (BLM). Brush-border-membrane-(BBM)-associated enzymes, sucrase, lactase, maltase, leucine aminopeptidase, and alkaline phosphatase also showed a marked reduction. Substrate saturation kinetics revealed the nature of inhibition was of mixed type in the case of sucrase, lactase, maltase, and alkaline phosphatase (Km was increased, while Vmax decreased), whereas it was of non-competitive type for leucine aminopeptidase (Km was unchanged, while Vmax decreased). In vitro addition of cimetidine (5-20 mM) to the BBM also inhibited the enzyme activity. Dixon plot produced the inhibition constant (Ki) for cimetidine in the case of maltase, alkaline phosphatase, and leucine aminopeptidase in the order of 14.83, 32.83 and 11.5 mM, respectively. Analysis of lipids revealed a significant reduction in BBM-associated phospholipid and phospholipid/cholesterol molar ratio, while the neutral lipid fraction, i.e., cholesterol and triglycerides were not altered. Free fatty acid exhibited an increase after drug treatment, which was significant at higher dose after 24 h of single and 15 days of daily treatment. BLM-associated lipids did not exhibit any significant change. Cimetidine-induced depression in renal BLM- and BBM-associated disaccharidases and ATPases, at least at the higher dose level, may have serious consequences in the absorption of end-product nutrients.
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PMID:Depression of membrane-bound hydrolases by cimetidine in mouse renal basolateral and brush border. 183 34

The present study intended to evaluate the influences of Metagonimus yokogawai on the activities of brush border membrane bound enzymes of the small intestine. Mice were infected with 500 metacercariae respectively, and the worm recovery, morphological changes and enzyme activities were observed chronologically. A part of them were followed after the treatment. Recovered worms decreased in number continuously after the infection, and they were less than 10% after 2 weeks and almost zero after 28 weeks. Villous atrophy and stromal inflammation were found at two locations of the proximal jejunum from 2 weeks to 4 weeks after the infection. The enzymes, alkaline phosphatase, leucine aminopeptidase and disaccharidases (sucrase, lactase, maltase, and trehalase), showed lowered activities in the duodenum and proximal jejunum of the infected mice but they increased in the distal jejunum for the first two weeks. From three weeks after the infection, the activities were gradually recovered. In one week treated mice, they recovered the activities at 2 weeks from the treatment, but there found no differences of the activities between the 3 week treated group and infected controls. The present data reveal that M. yokogawai infection induces degenerative changes of the host's intestinal mucosa not only morphologically but functionally during the initial phase of infection. The lowered enzyme activities in acute metagonimiasis should be associated with malabsorption and diarrhea.
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PMID:Activities of brush border membrane bound enzymes of the small intestine in Metagonimus yokogawai infection in mice. 191 29

Oral administration of embelin (75 mg/kg per day, daily for 15 and 30 days) to male rats caused significant elevation in the uptake of D-glucose, L-alanine, L-leucine and calcium in small intestinal segments. Embelin also produced significant increases in intestinal brush border membrane-associated enzymes (sucrase, lactase, maltase, alkaline phosphatase and leucine aminopeptidase) in both intestinal homogenates and partially purified brush border membrane preparations. Significant increases were also noted for microsomal glucose-6-phosphatase and cytosolic lactate dehydrogenase. Increase in brush border membrane-associated total lipids, phospholipids, cholesterol, triacylglycerol, unesterified fatty acids and ganglioside sialic acid were seen but not in the cholesterol/phospholipid molar ratio. All these changes returned to control or near control levels following withdrawal of the drug.
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PMID:Effects of embelin, a male antifertility agent, on absorptive and digestive functions of rat intestine. 192 15

In the present experiments, selective quenching by trinitrophenyl groups as well as steady-state fluorescence polarization and differential polarized phase fluorescence techniques, using three different lipid soluble fluorophores, were used to directly examine the fluidity of the exofacial and cytofacial leaflets of rat small intestinal brush-border membranes. These studies revealed that the fluidity of the exofacial hemileaflet was greater than the cytofacial hemileaflet. Differences in the distribution of phosphatidylcholine and phosphatidylethanolamine, as assessed by phospholipase A2 treatment and trinitrophenylation of aminophospholipids, were, at least partially, responsible for the asymmetrical fluidity of the hemileaflets. Moreover, in vitro addition of benzyl alcohol (final concn 25 mM) preferentially fluidized the exofacial leaflet and concomitantly decreased leucine aminopeptidase activity but did not affect the activities of maltase, sucrase, alkaline phosphatase, or gamma-glutamyltranspeptidase. In vivo addition of the membrane-mobility agent 2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)octanate] (A2C) (final concn 7.5 microM) preferentially fluidized the cytofacial leaflet and increased Na(+)-gradient-dependent D-glucose transport but not Na(+)-gradient-dependent L-leucine transport.
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PMID:Characterization and modulation of rat small intestinal brush-border membrane transbilayer fluidity. 201 33

The effects of increasing environmental temperature and of exercise on some biochemical characteristics of the intestinal mucosa were analyzed in hamsters to determine whether damage occurs to the intestine during exercise, because long-distance runners complain of cramp, diarrhea, or retrostaltic symptoms, especially when exercise is performed at high temperatures. Two sets of experiments were carried out on groups of five animals. First, one group stayed at rest at 20 degrees C while another group performed exercise for 30 min at the same temperature. Second, one group of animals remained at rest at 20 degrees C for 16 h, a second group was placed at 32 degrees C for the same period, and a third group was subjected to the latter treatment but in addition performed two 20-min exercises. The animals were killed immediately after the experiment. After the small bowel was removed, biopsies were taken for histological examination, and the remaining small bowel tissue was homogenized for biochemical analysis. During exercise performed at 20 degrees C or during exposure to 32 degrees C, the DNA weight (expressed as a function of the protein weight) increased; the specific activity of sucrase, leucine aminopeptidase, diamine oxidase, and maltase decreased; spermine and putrescine content generally decreased; and the weight of mucosal proteins per length of intestine did not vary significantly. When exercise was performed at 32 degrees C, we noted few modifications in the values of the intestinal parameters tested, i.e., changes in only the weight of mucosa expressed as a function of bowel length and, perhaps, the spermine or putrescine content.
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PMID:Effects of environmental temperature and exercise on the biochemical characteristics of hamster intestine. 202 50

Administration of Embelin, an experimental antifertility agent, to male rats (20 mg/kg body wt/day, daily for 15 and 30 days), caused an elevation in the uptake of D-glucose, L-alanine, L-leucine, and calcium in the small intestinal segments. An increase was also noted in the intestinal brush border membrane (BBM)-associated enzymes, sucrase, lactase, maltase, alkaline phosphatase, and leucine aminopeptidase in both the intestinal homogenates and partially purified BBM preparations, particularly after 30-day administration of the drug. Embelin treatment also caused a significant increase in the microsomal glucose-6-phosphatase and the cytosolic enzyme, lactate dehydrogenase. In the Embelin-treated animals BBM-associated total lipids, phospholipids, cholesterol, triacylglycerol, unesterified fatty acids, ganglioside-sialic acids as well as the cholesterol/phospholipids molar ratio showed a considerable increase. All these changes in the Embelin-treated animals were restored back to the normal or near normal biochemical makeup when the drug therapy was withdrawn and the animals were allowed to recover for another 15 and 30 days, respectively.
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PMID:Changes in glucose/amino acid/calcium uptake and brush-border membrane-associated enzymes in rat small intestine after the administration of embelin (plant benzoquinone), an antifertility agent. 211 47

Effect of glutamine supplementation to parenteral nutrition on small intestinal function was evaluated in malnourished rats as well as normal rats. Animals were administered the solution supplemented with glutamine at 20% of total amino acids either intravenously or intragastrically for seven days. Intragastrically fed rats gained more weight than parenterally fed rats. In malnourished rats, whose small intestinal weight was decreased to 60% by feeding protein-free diet for four weeks or by fasting for seven days, small intestinal weight was further decreased by intravenous infusion but was maintained at the pre-infusion level by intragastric infusion. The intragastric administration of glutamine increased small intestinal weight and mucosal brush border enzyme activities of sucrase, leucine aminopeptidase and alkaline phosphatase, showing the beneficial effect of intragastrically administered glutamine to maintain small intestinal function. In parenteral nutrition, however, it seems that more than 20% supplementation of glutamine relative to total amino acids might be necessary to mitigate intestinal atrophy.
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PMID:Comparative effect of intravenously or intragastrically administered glutamine on small intestinal function of the rat. 212 78

Effects of feeding high-protein (HP) and high-fat (HF) diets to lactating rats have been studied on the development of microvillus membrane enzymes and glycosylation in suckling rats. The activities of sucrase and lactase were significantly (P less than 0.01) decreased in the pups reared on HP fed dams. Alkaline phosphatase (AP), leucine aminopeptidase (LAP) and gamma-glutamyl-transpeptidase (gamma-GTP) activities were essentially similar in HP and pair-fed groups. Pups reared on dams fed HF-diet, revealed nearly a 20% increase in disaccharidase levels and a significant (P less than 0.05) decrease in AP activity compared to the pair-fed controls. The activities of LAP and GTP were unaffected under these conditions. Sialic acid content was unaltered, however, fucose level of the membranes was significantly reduced in pups nursed by mothers fed HP-(P less than 0.05) or HF-(P less than 0.01) diet. The binding of 125I-labelled wheat germ agglutinin and Ulex europeus agglutinin was in agreement to the data on sialic acid and fucose contents of the membranes. The binding of peanut agglutinin to microvillus membranes was enhanced by 31% and 21% in HP and HF groups, respectively. These findings suggest that the quality of maternal nutrition affects the enzymes and glycosylation of brush-borders in developing rat intestine.
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PMID:Maternal nutrition and development of intestinal functions: II--Effect of feeding high protein and high fat diets to lactating rats. 225 72


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