Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.20 (alpha-glucosidase)
4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamine (GLN) is an important fuel and epidermal growth factor (EGF) is a potent mitogen for intestinal mucosa cells. GLN-enriched parenteral nutrition was administered to male Wistar rats, and subcutaneous injections of EGF were given for 3, 6, and 7 days. Control animals were fed a non-GLN-containing solution. Other groups of animals received GLN or EGF alone. Mucosal samples were obtained from the jejunum, ileum, and colon for measurement of weight, DNA, protein, and mucosal thickness. Disaccharidase activity was measured in the jejunum. After 3 days, only animals that received both GLN and EGF had a significant increase in small-bowel mucosal protein and thickness relative to controls. A similar pattern was observed in the colon, where animals that received both agents had a greater mucosal thickness, DNA, and protein content than controls. At 7 days, animals that received EGF or GLN had greater nitrogen retention. In addition, animals that were treated with EGF had elevated sucrase and maltase activity compared with GLN-fed animals at this time. Animals treated with GLN and EGF tended to have increased sucrase activity relative to controls. GLN feeding was associated with increased mucosal DNA and protein contents throughout the intestine for the combined series. EGF increased mucosal DNA and protein in the small intestine but not in the colon. The effect of EGF on the protein content of the small-bowel mucosa was dose dependent. The effects of GLN and EGF on the small bowel and colonic mucosa were additive. These studies suggest that specific nutrients and hormones may be used in combination to decrease the mucosal atrophy that commonly occurs after gut disuse or disease.
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PMID:Combined effects of glutamine and epidermal growth factor on the rat intestine. 313 28

In vivo biochemical indices of nephrotoxicity were investigated in Fischer 344 rats treated with a new platinum analog, tetraplatin [tetrachloro(dl-trans)1,2-diaminocyclohexane platinum(IV), NSC-363812], in comparison with rats receiving equimolar dosages of cisplatin and CHIP [cis-dichloro,trans-dihydroxybis-isopropylamine platinum(IV), NSC-256927]. The goals of this study were to assess the comparative nephrotoxicities and to determine which battery of tests might be useful for the assessment of platinum analog-induced nephrotoxicity in future clinical investigations of these drugs. An iv bolus injection of 6.7, 13.3, 26.7, and 53.3 mumol/kg of each drug in saline was administered and assessment of biochemical parameters was conducted for 15 days postinjection. A combination of urinary enzyme and protein excretion rates along with blood urea nitrogen (BUN) determinations was used to assess the nephrotoxicity of these compounds. At equimolar dosages, tetraplatin appeared to be less nephrotoxic than cisplatin, and CHIP was not nephrotoxic. At all dosages tested, cisplatin increased the rate of urinary excretion of protein, lactate dehydrogenase (LDH), and N-acetylglucosaminidase (NAG) between Days 1 and 5. Tetraplatin did not affect these parameters until the 13.3 mumol/kg dosage. Cisplatin had little effect on the excretion rates of the brush border enzymes alkaline phosphatase and maltase, whereas tetraplatin caused an initial elevation with delayed onset of peak excretion rates at 8 days postinjection. Changes in BUN were not evident until after the 13.3 mumol/kg dosage of cisplatin and the 26.7 mumol/kg dosage of tetraplatin. BUN was useful for ranking the relative toxicities of the three compounds tested, but was not as sensitive in detecting the onset of injury that correlated with early histopathological changes. Tetraplatin appeared to be less nephrotoxic than cisplatin on an equimolar basis and the specific manifestations of its toxicity were different from those observed with cisplatin. Urinary excretion rates for LDH, NAG, and protein proved to be sensitive indicators of platinum analog-induced nephrotoxicity. These indices, combined with BUN determinations and functional assessments, facilitated comparisons of the nephrotoxicity induced by cisplatin and tetraplatin in rats.
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PMID:In vivo biochemical indices of nephrotoxicity of platinum analogs tetraplatin, CHIP, and cisplatin in the Fischer 344 rat. 335 Feb 30

An experiment was conducted to examine the effect of pathogenic Escherichia coli inoculated into the yolk sac of day-old turkeys. Escherichia coli was isolated from the yolk sac of stunted poults and inoculated directly into the yolk sac of day-old birds. Poults were administered either .1 ml of uninoculated sterile Todd-Hewitt broth or .1 ml of a 10(-3) or 10(-2) dilution of a 24-hr E. coli culture containing 3.4 X 10(8) viable bacteria/ml. In addition, poults were fed either 28 or 22% protein diets from 0 to 21 days of age to form a 3 X 2 factorial arrangement. Body weight gain and feed consumption were measured weekly, and dry matter and protein retention and nitrogen-corrected metabolizable energy were measured from 7 to 10 and 17 to 20 days postinoculation. Intestinal mucosal dipeptidase and maltase activities were determined at 21 days of age. Average mortality by 7 days of age was increased from 1 to 36% from the E. coli inoculation of the yolk sac. Escherichia coli significantly depressed body weight gain and feed consumption 27 and 30, 13 and 16, and 6 and 8%, respectively, during the first, second, and third weeks of the experiment but failed to affect feed efficiency. Feeding a 28% protein diet alleviated the depression in feed consumption and body weight gain to some extent compared with a substantial depression at 22% protein. Nitrogen content and gross energy of the excreta were increased by both dilutions of E. coli for the 7 to 10-day period; this was indicative of a malabsorption of nutrients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary protein and yolk sac inoculation with Escherichia coli in young turkeys. 389 12

A chronological study was carried out on 50 male Wistar rats (350 g) to determine the effects of 3 days of fasting and 16 h to 9 days of refeeding on the morphology of jejunal and ileal mucosa (villus, crypt and enterocyte heights; number of mitosis), on some aspects of their functional adaptation (sucrase, maltase, protein) and on nitrogen and lipid absorptions. Three days of fasting resulted in weight loss (12 p. 100), in a jejunal mucosa atrophy (villus height: 376 +/- 18 vs. 492 +/- 4 microns in controls; enterocyte height: 31 +/- 2 vs. 41 +/- 0.3 micron in controls) and a decrease in disaccharidases activities (sucrase: 927 +/- 90 vs. 3,363 +/- 21 mU/10 cm length in controls). No change in ileal mucosa morphometry was noticed. Ad libitum refeeding caused a rapid and progressive weight gain, a jejunal morphometric regrowth identical to control values at 16 h (villus height: 521 +/- 20, enterocyte height 42 +/- 0.9 microns), and maximum at 40 h of refeeding (villus height: 601 +/- 5 microns). Disaccharidases adaptation was delayed, with a maximum at 64 h of refeeding (sucrase: 3,524 +/- 56 mU/10 cm length). Despite a 30 p. 100 increase of food consumption over the whole study (45 p. 100 during the first 16 h of refeeding), nitrogen and lipid absorption coefficients remained identical to those found in controls with an increased nitrogen balance of 70 p. 100 at 16 h and 54 p. 100 at 40 h refeeding, as compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of fasting and refeeding on the adaptation of the small intestine in rats. A model for physiopathologic studies]. 408 42

The relative merits of a comprehensive series of contemporary methods for detection of acute nephrotoxicity were evaluated. Male Sprague-Dawley rats were given 0, 0.25, 0.5, 1.0, or 3.0 mg mercuric chloride (HgCl2)/kg body weight by ip injection. Indices of nephrotoxicity were examined 8, 24, 48, 72, and 96 h later. Alterations in urine osmolality, volume, and protein levels were seen within 24 h in response to 1 mg/kg or more of HgCl2. Administration of 0.5-3.0 mg/kg produced dose-dependent increases in urinary excretion of maltase activity and glucose by 24 h, the period of peak effect. There was no increase in maltase or alkaline phosphatase (AP) activity in the serum of these animals. Enzymuria was not apparent in rats that had marked elevations in serum AP, argininosuccinate lyase, and ornithine carbamyl transferase activities as a result of physical (i.e., dichlorodifluoromethane-frozen) or chemical (carbon tetrachloride-induced) damage of the liver. Morphological alterations, in the proximal tubular epithelium of perfusion-fixed kidneys from HgCl2-dosed rats, paralleled the changes in enzyme excretion with respect to time of onset and dose-effect. There was a dose-dependent inhibition of tetraethylammonium (TEA) and p-aminohippurate (PAH) uptake by renal cortical slices at 24 h. Interestingly, increases in uptake of TEA and PAH were seen 8 h after a 1-mg/kg dose. Clearance of inulin and PAH in vivo were altered at 8 h by 0.5 and 1 mg/kg. Marked depression of these functional indices was seen at 24 h, by which time blood urea nitrogen (BUN) levels were increased. The 0.5- and 1.0-mg/kg doses also produced time- and dose-dependent increases in intracellular Na+ content which were maximal at 24 h. These results illustrate the importance of using a combination of biochemical and functional tests to elucidate the sequence of events in the kidney following toxic insult. Nevertheless, some of the simpler, traditional techniques (e.g., histopathology, urinalyses, BUN) were sensitive and organ-specific, and should continue to be very useful in nephrotoxicity testing/screening.
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PMID:Assessment of functional, morphological, and enzymatic tests for acute nephrotoxicity induced by mercuric chloride. 622 7

Bacillus anthracis could be distinguished from the taxonomically related species B. cereus, B. mycoides, and B. thuringiensis by a comparison of glycosidase activities. All the bacilli tested possessed alpha-glucosidase activity, as evidenced by the hydrolysis of p-nitrophenyl-alpha-D-glucoside. In B. anthracis, the glucosidase activity could be enhanced by the addition of agents which damage cellular surface structures. Treatment of B. anthracis strains with toluene. Triton X-100, or mutanolysin or cellular disruption by sonication resulted in higher rates of alpha-glucoside hydrolysis than were accomplished by cells suspended in buffer. It is suggested that intact B. anthracis cells have a limited permeability to the glucosidase substrate. In contrast to the results obtained for B. anthracis, Triton X-100 markedly diminished the enzymatic hydrolysis of p-nitrophenyl-alpha-D-glucoside by strains of B. cereus, B. mycoides, and B. thuringiensis. Triton X-100 also enhanced the alpha-maltosidase activity of B. anthracis but not that of the other bacilli. B. mycoides possessed an apparently inducible N-acetylglucosaminidase although the enzyme was absent in B. anthracis. The glucosaminidase was inducible in the presence of p-nitrophenyl-N-acetylglucosamine in the absence of conventional nitrogen sources. Chloramphenicol prevented the induction of the glucosaminidase in B. mycoides. In several B. cereus and all B. thuringiensis strains, the glucosaminidase was constitutive. The results suggest a means for the rapid laboratory differentiation of B. anthracis from other closely related bacilli. Assays for alpha-glucosidase and alpha-maltosidase, in the presence and absence of Triton X-100, can be used to distinguish B. anthracis from B. cereus, B. mycoides, and B. thuringiensis. Similarly, the hydrolysis of p-nitrophenyl-beta-N-acetylglucosamine induced by B. mycoides but not by B. anthracis provides an additional means for differentiating these similar bacilli.
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PMID:Glycosidase activities of Bacillus anthracis. 642 87

The conformations of nitrogen-in-the-ring sugars and their N-alkyl derivatives were studied from 1H NMR analyses, mainly using 3J(H,H) coupling constants and quantitative NOE experiments. No significant difference was seen in the ring conformation of 1-deoxynojirimycin (1), N-methyl-1-deoxynojirimycin (2), and N-butyl-1-deoxynojirimycin (3). However, it was shown that the C6 OH group in 1 is predominantly equatorial to the piperidine ring, while that in 2 or 3 is predominantly axial, and its N-alkyl group is oriented equatorially. In the furanose analogues 1,4-dideoxy-1,4-imino-D-arabinitol (4) and its N-methyl (5) and N-butyl (6) derivatives, the five-membered ring conformation differed significantly by the presence or absence of the N-substituted group and the length of the N-alkyl chain. Compound 3 reduced its inhibitory effect on almost all glycosidases, resulting in an extremely specific inhibitor for processing alpha-glucosidase I since N-alkylation of 1 is known to enhance both the potency and specificity of this enzyme in vitro and in vivo. This preferred (C6 OH axial) conformation in 2 and 3 appears to be responsible for their strong alpha-glucosidase I activity. Compound 4 is a good inhibitor of intestinal alpha-glucohydrolases, alpha-glucosidase II, and Golgi alpha-mannosidases I and II, but its N-alkyl derivatives 5 and 6 markedly decreased inhibitory potential for all enzymes tested. In the case of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP, 7), which is a potent beta-galactosidase inhibitor, its N-methyl (8) and N-butyl (9) derivatives completely lost potency toward beta-galactosidase as well. N-Alkylation of compounds 4 and 7, known well as potent yeast alpha-glucosidase inhibitors, resulted in a serious loss of inhibitory activity toward yeast alpha-glucohydrolases. Activity of these nine analogues against HIV-1 replication was determined, based on the inhibition of virus-induced cytopathogenicity in MT-4 and MOLT-4 cells. Compounds 2 and 3, which are better inhibitors of alpha-glucosidase I than 1, proved active with EC50 values of 69 and 49 micrograms/mL in MT-4 cells and 100 and 37 micrograms/mL in MOLT-4 cells, respectively, while none of the furanose analogues exhibited any inhibitory effects on HIV-1. The change in potency and specificity of bioactivity by N-alkylation of nitrogen-in-the-ring sugars appears to be correlated with their conformational change.
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PMID:N-alkylated nitrogen-in-the-ring sugars: conformational basis of inhibition of glycosidases and HIV-1 replication. 760 1

It has been reported that aortic homografts that have been cryopreserved before transplantation remain viable longer as an allograft than tissue stored at 4 degrees C in an antibiotic solution. In the present study, we tested the hypothesis that storage of cardiac valve tissue by cryopreservation or by antibiotic preservation may alter the metabolic status of the tissue. Initially, we collected aortic valves composed of cardiac tissue, aortic root, and valvular tissue from cadaver donors. These specimens were divided into three equal portions, and one portion was analyzed before storage while the other two parts were stored for 3 weeks at either 4 degrees C in an antibiotic solution or at -196 degrees C in liquid nitrogen. All specimens were examined with regard to the following parameters: tissue structure, tissue viability, cell proliferative capacity, metabolic function, and identification of cell-specific antigens. We found no significant alterations in the structure of any of the three tissue components after antibiotic preservation or cryopreservation; however, cell viability and cell number were decreased in all three groups. All tissue samples grew in culture before storage. When we compared activities of the following organellar marker enzymes--lysosomal acid lipase, plasma membrane 5' nucleotidase, mitochondrial cytochrome oxidase, and microsomal neutral alpha-glucosidase--we observed no major differences between tissues stored by either technique. In addition, we observed no loss of enzymic activity as a result of storage. Finally, when cell lines isolated from each tissue specimen were incubated with monoclonal antibodies against cell-specific antigens in an immunoperoxidase assay, all the cell cultures proved to be endothelial cells. These results suggest that although cardiac valve tissue stored by cryopreservation or by antibiotic preservation retained its normal structure and metabolic capabilities, both storage techniques produced significant decreases in cell numbers and viability. However, only endothelial cells from tissue stored by cryopreservation retained the capacity to proliferate in vitro. These findings have important implications for the function of aortic homografts transplanted after storage.
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PMID:Biochemical and cellular characterization of cardiac valve tissue after cryopreservation or antibiotic preservation. 766 4

Seven pyranoses and three furanoses with a nitrogen in the ring were prepared by chemical synthesis, microbial conversion, and isolation from plants to investigate the contribution of epimerization, deoxygenation, and conformation to the potency of inhibition and specificity of mammalian glycosidases. The seven pyranoses are 1-deoxynojirimycin (1), the D-manno (2), D-allo (3), and D-galacto (4) isomers of 1, fagomine (1,2-dideoxynojirimycin, 5), and the D-allo (6) and D-galacto (7) isomers of 5, while the three furanoses are 2,5-dideoxy-2,5-imino-D-mannitol (8), 1,4-dideoxy-1,4-imino-D-arabinitol (9), and 1,4-dideoxy-1,4-imino-D-ribitol (10). The 2-deoxygenation and/or 3-epimerization of 1 enhanced the potency for rat intestinal lactase and bovine liver cytosolic beta-galactosidase. Especially compound 6 showed a potent inhibitory activity against both enzymes, and compound 8, a mimic of beta-D-fructofuranose, was a potent inhibitor of both beta-galactosidases as well. Compound 4, which has been known as a powerful alpha-galactosidase inhibitor, exhibited no significant inhibitory activity for most of mammalian beta-galactosidases. In addition, compound 6 fairly retained a potency of 1 toward rat intestinal isomaltase. In this study, compound 8, known as a processing alpha-glucosidase I inhibitor in cell culture, has been found to have no effect on processing alpha-glucosidase II, whereas 9 has been shown to be a good nonspecific inhibitor of intestinal isomaltase, processing alpha-glucosidase II, Golgi alpha-mannosidases I and II, and porcine kidney trehalase. It has been speculated that glycosidase inhibitors have structures which resemble those of the respective glycosyl cations. This Broad inhibitory activity of 9 toward various glycosidases suggest that it superimposes well on the various glycosyl cations.
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PMID:Nitrogen-in-the-ring pyranoses and furanoses: structural basis of inhibition of mammalian glycosidases. 796 30

Total parenteral nutrition (TPN) is associated with atrophic changes in the structure and function of the intestinal mucosa. Because rapidly renewing intestinal mucosal cells may require an external source of purines and pyrimidines for their optimal growth, it can be assumed that supplementation of nucleosides and a nucleotide mixture (OG-VI) during TPN may prevent the progression of mucosal atrophy by compensating for a relatively insufficient delivery from liver. To test that hypothesis, male Wistar rats receiving TPN for 7 days were divided into four groups according to different TPN solutions. Group C (n = 10) received a standard solution, group O (n = 10) received OG-VI in addition to the standard solution, and group G (n = 10) received a glutamine-rich TPN solution containing almost the same amount of calories and nitrogen as the standard solution. Group O+G (n = 10) received OG-VI in addition to the glutamine-rich solution. Various parameters were examined on the eighth day in the jejunal and ileal segments. The following significant changes in comparison with group C were observed: total wet weight of the jejunal segment in group O was significantly greater, as was mucosal wet weight of the jejunal and ileal segments in groups O and O+G; protein contents of the ileal segment in group O as well as the DNA content of the jejunal segment in group O increased significantly; and maltase activity of the jejunal segment in group O+G increased, as did the villus height of the jejunal segment in groups O and O+G and the villus height of the ileal segment in group G.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intravenous administration of nucleosides and a nucleotide mixture diminishes intestinal mucosal atrophy induced by total parenteral nutrition. 809 74


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