Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.20 (alpha-glucosidase)
 4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of the treatment schedule of dianhydrogalactitol on its effect on the activity of mucosal enzymes in rat intestine was studied. The effect of a single high dose (10 mg/kg) was compared with that of repeated small doses (4 x 2.5 mg/kg) given at daily intervals. At 48 h after a single high dose the activities of thymidine kinase, which is a marker of dividing crypt cells, and of alkaline phosphatase, sucrase, maltase, xanthine oxidase, which are markers of mature enterocytes, were strongly depressed. Even 96 h after the treatment low enzyme activities could be observed. Repeated small doses caused milder enzyme inhibition and almost total recovery had occurred by 96 h after administration of the last dose. The results indicate that fractionation of drug administration can reduce the toxic side-effects on the intestinal mucosa and might be partly responsible for the higher therapeutic index of such schedules in experimental tumor models.
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PMID:Effect of a single high dose and repeated small doses of dianhydrogalactitol (DAG; NSC-132313) on rat intestinal mucosa. 641 95

The effect of resuming food intake after a period of starvation (refeeding) on the specific activities of selected rat intestinal enzymes was determined. The rate of weight gain was higher in refed animals than in control animals, without a difference in food intake. Fasting caused intestinal atrophy which reversed rapidly on refeeding. Fasting decreased the specific activities of sucrase, maltase, and galactokinase, but did not affect the specific activities of hexokinase, pyruvate kinase, or crypt thymidine kinase. Sucrase, maltase, hexokinase, pyruvate kinase, and thymidine kinase specific activities all rose above control values during refeeding. The overshoot in intestinal enzyme specific activities may help promote the rapid weight gain observed in refed rats and is an integral part of the total adaptation to fasting and refeeding.
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PMID:Refeeding after a fast in rats: effects on small intestinal enzymes. 705 2

Selective protection of the normal host tissues from the toxic effects of anticancer agents would allow the use of higher, probably more effective, doses of the drugs. It has been demonstrated that delayed high-dose uridine administration after 5-fluorouracil decreases the extent of myelosuppression and causes faster regeneration of the bone marrow. We studied the biochemical consequences of the gastrointestinal toxicity caused by 5-fluorouracil and the potential of high-dose uridine treatment to influence these adverse effects. 5-Fluorouracil caused dose-related decreases in the biochemical parameters (thymidine kinase, sucrase, maltase, alkaline phosphatase) selected as early markers of the impaired metabolic activity of the intestinal mucosa. The nadir of the biochemical changes was reached between 24 h and 72 h after 5-fluorouracil treatment, and complete regeneration of the mucosa took 6-7 days. Delayed high-dose uridine administration failed to mitigate the severity of the gastrointestinal damage that ensued after 5-fluorouracil treatment, but caused significantly earlier regeneration of the mucosa.
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PMID:Biochemical consequences of 5-fluorouracil gastrointestinal toxicity in rats; effect of high-dose uridine. 850 Feb 30

This study investigated the effect of clinical and subclinical vitamin A deficiency on intestinal structure and function in rats. Weanling male rats fed a vitamin A-deficient diet (VA-) for 40-42 or 60-63 d were compared with rats either pair-fed (PF) or with free access to the same diet supplemented with vitamin A (VA+). A reference (REF) group was fed a standard rat diet. Weight began to plateau in VA- rats after 42 d, becoming significantly different from PF rats at 60-63 d (P < 0.02). Diarrhea did not develop in any study group. VA- rats had clinical signs of vitamin A deficiency in the 60-63 d study, but not in the 40-42 d study. However, serum and liver retinol concentrations were negligible in all VA- rats. VA- rats in the 60-63 d study had significantly reduced villus height (P < 0.02), and sucrase and maltase activities (P < 0.02) compared with PF rats. There were no differences between VA- and PF rats in mucosal wet weights, protein and DNA concentrations, thymidine kinase activity and glucose transport. No differences were detected in the 40-42 d study for any variable measured. Because clinical vitamin A deficiency in rats causes only mild changes in intestinal structure and function, it is unlikely that these alterations alone are responsible for the interactions observed in epidemiological studies between vitamin A deficiency and diarrheal disease.
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PMID:Vitamin A-deficient rats have only mild changes in jejunal structure and function. 868 43

Uridine diphosphoglucose (UDPG) is a precursor of uridine that can be used as a rescuing agent from 5-fluorouracil (5FU) toxicity. Four doses of UDPG (2000 mg/kg i.p. or p.o. at 2, 6, 24, and 30 h after 5FU bolus) allowed the escalation of a weekly bolus of 5FU from 100 mg/kg (5FU100) to 150 mg/kg (5FU150) in healthy and tumor-bearing BALB/c, C57/BI, and CD8F1 (BALB/c x DBA/8) mice. 5FU150 without rescuing agents is not tolerated by the animals. When followed by UDPG, on the contrary, it is possible to increase the dose of 5FU even when it is modulated by leucovorin. Toxicity was the same for 5FU100 and 5FU150 + UDPG, and the nadir values (expressed as a percentage of pretreatment values) were 83 and 85% for weight, 45 and 45% for hematocrit, and 45 and 61% for leukocytes, respectively. Platelets were not affected by treatment. A protective effect was also shown for the gastrointestinal tract. The enzymes thymidine kinase, maltase, and sucrase were measured in the intestinal mucosa at different times after 5FU treatment with or without UDPG rescue. Even if the nadir values in enzyme activities were similar in mice receiving or not receiving UDPG, the pattern of recovery showed that cell repopulation was more rapid in the group treated with UDPG. 5FU150 + UDPG had enhanced antitumor activity against CD8F1 mammary carcinoma and against the resistant tumor Colon 26 (tumor doubling time 1.9 days for controls, 8.5 days for 5FU100, 13.7 days for 5FU150 + UDPG, and 15.9 days for 5FU150 + leucovorin + UDPG). We demonstrated that UDPG administered at 2, 24, and 30 h after 5FU100 does not reduce the antitumor activity of 5FU in two sensitive tumors (Colon 38 and Colon 26-10). In conclusion, UDPG is a promising rescuing agent for 5FU; it reduces the toxic side effects and increases the therapeutic index.
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PMID:Modulation of 5-fluorouracil in mice using uridine diphosphoglucose. 981 88


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