Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anti-ulcer effects of cetraxate, a new compound possessing anti-plasmin, anti-casein and anti-trypsin actions were investigated by using experimental gastric ulcer models in rats. Cetraxate, 300 mg/kg p.o. showed significant inhibitory effects of 65.3%, 70.0%, 30.2%, and 67.1% against aucte types of ulcers producing by aspirin, phenylbutazone, indomethacin, and pyloric ligature (Shay's ulcer), respectively. These effects were greater than those obtained by gefarnate and aluminum sucrose sulfate may be mainly attributed to the protecting action of this drug on gastric mucosa. Ctraxate further revealed remarkable inhibitory effects on chronic types of ulcers produced by acetic acid, clamping, and clamping-cortisone. In acetic acid ulcer in particular, cetraxate was found to have a dose-dependent inhibitory effect at doses over 50 mg/kg. Of test drugs including L-glutamine and methylmethionine sulfonium chloride, cetraxate showed the most remarkable inhibitory effect on beta-glucuronidase activity in ulcer tissue of these three types of ulcers. These findings suggest that cetraxate may prevent the connective tissue in the ulcer location from decomposition due to lysosomal enzymes such as beta-glucuronidase, thereby accelerating the recovery from ulcer.
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PMID:Anti-ulcer effects of 4'-(2-carboxyetyl) phenyl trans-4-aminomethyl cyclohexanecarboxylate hydrochloride (cetraxate) on various experimental gastric ulcers in rats. 100 3

The health of the respiratory tracts of 19 horses was studied for 11 months. The horses were placed into 3 groups (healthy, periodically diseased and continuously diseased) based on the measurements of blood gases, intrapleural pressure and on neutrophil content of tracheal mucus. Lysosomal enzymes (N-acetyl-beta-D-glucosaminidase and beta-glucuronidase) and reflectors of the proteolytic system (plasmin, plasminogen, trypsin inhibitor capacity) were determined. beta-glucuronidase appeared to be a good indicator of the presence of disease of the respiratory system. High beta-glucuronidase values were seen in horses with elevated numbers of neutrophils, elevated arterial alveolar and intrapleural differences as well as in diseased horses during the stabling period. Trypsin inhibitor capacity seemed to be lower in the diseased respiratory system, probably due to the increased consumption of trypsin inhibitors.
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PMID:Beta-glucuronidase and trypsin inhibitor capacity of tracheal lavage fluid as indicators of seasonal airway irritation in the horse. 798 42

Seventeen trotters, eight healthy and nine with a mild respiratory disease, underwent a submaximal treadmill exercise. Heart rate, breathing frequency, intrapleural pressure difference (IP difference) as well as haematocrit and concentration of lactic acid in blood were monitored before exercise, during exercise and during recovery. The activities of beta-glucuronidase and plasmin, total proteolytic activity and trypsin inhibitory capacity were measured from the tracheal fluid before and after exercise. IP difference significantly increased during exercise and returned to normal values within 15 min in healthy horses. Differences in intrapleural pressure between healthy and diseased horses were not significant during exercise. Increase of the respiratory rate was monitored during recovery probably due to respiratory compensation of the lactic acidosis. Activities of beta-glucuronidase increased and activities of plasmin and trypsin inhibitory capacity decreased due to exercise. Most prominent changes were seen in the decrease of plasmin activity. The total proteolytic activity in the tracheal fluid before exercise correlated with the VLa4 values, indicating that a mild respiratory disease, which causes proteolysis in the respiratory tract, decreases performance capacity of the horse.
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PMID:Effect of exercise on enzymatic activity in tracheal fluid and on intrapleural pressure difference in horses. 857 6

Intrauterine fluid (IUF) was collected using a tampon from mid-oestrous mares (n = 57) with and without ultrasonically detectable accumulations of free intraluminal fluid. Bacteria were cultured and neutrophils counted from all samples (n = 57). Total protein concentration, trypsin-inhibitor capacity (TIC), and plasmin, beta-glucuronidase (B-Gase) and N-acetyl-beta-D-glucosaminidase (NAGase) activities were determined in 27 IUF samples. The motility of spermatozoa in the presence of IUF, IUF extended with Kenney's medium (1:1) and Kenney's medium alone was analysed in 9 samples using a Hamilton-Thorn motility analyser. Thirty-five mares were inseminated immediately after collection of IUF, and every second day until ovulation. Embryos were recovered nonsurgically 6 days after ovulation. After embryo transfer, fluid accumulations were recorded during oestrus and an endometrial biopsy specimen taken (n = 53). In the beginning of oestrus, fluid accumulations were detected in 39% (22/57) of mares, while on the day when IUF was collected, fluid accumulations were observed in 26% (15/57) of mares. The fluid was anechogenic, and in 80% of the mares located in the uterine body. None of the mares exhibited cytological or bacteriological evidence of acute endometritis. Total protein concentrations, TIC and B-Gase activities in IUF were statistically significantly lower in mares with fluid accumulations (n = 14) than in mares without fluid accumulations (n = 13) (p < 0.01). The addition of undiluted IUF to extended semen significantly reduced total and progressive motilities, path velocities and percentages of rapid spermatozoa (p < 0.05) in vitro. On endometrial biopsy, fibrosis was found to be more prominent (p = 0.025) in mares with fluid accumulations (n = 9) than in mares without (n = 44). It was concluded that anechogenic fluid accumulations during oestrus were associated with compositional changes in IUF. Although IUF had negative effects on spermatozoal motility in vitro, the presence of fluid accumulations at the time of insemination did not affect embryo recovery rates.
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PMID:Intrauterine fluid accumulation in oestrous mares. 912 48

The aim of the study was to determine whether neutrophil numbers (PMN), trypsin-inhibitor capacity (TIC), lysozyme, N-acetyl-beta-D-glucosaminidase (NAGase), beta-glucuronidase (B-Gase), total protein, and plasmin in uterine lavage fluid of postpartum (p.p.) mares, either at the time of foal heat insemination or around the time of arrival of the embryo in the uterus, could be used in predicting conception. Fifteen mares were inseminated within 13 h after the first p.p. ovulation. Uterine lavage fluids were successfully collected from 9 out of 12 mares before insemination and from all 15 mares before embryo recovery 7 to 8 days after insemination. The embryo recovery rate was 53% (8/15). Prior to insemination, PMN, TIC and lysozyme levels were elevated in 3/4 mares not producing embryos. However, only 1/5, 1/5 and 0/5 mares producing embryos had elevated levels of PMN, TIC, and lysozyme, respectively. None of the parameters was significantly different in mares with or without embryos, but lysozyme was the closest to significance (p = 0.07). In both groups of mares, activities of NAGase (p < 0.01) and B-Gase (p < 0.05) were significantly higher in dioestrus than immediately after ovulation. At embryo recovery, NAGase was higher in mares not producing embryos (p < 0.05). The results suggest that a long-lasting inflammation is the best explanation for low pregnancy rates during the first p.p. oestrus. Further research is needed to establish whether lysozyme, or possibly TIC, could be used in predicting conception at foal heat.
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PMID:Relationship between embryo recovery rate and uterine lavage fluid composition in postpartum mares. 1108 65

In order to improve current chemotherapeutic treatment and diminish severe side effects, several prodrug strategies have evolved to achieve site-specific delivery of cytotoxic anticancer agents. This review concentrates on recent developments of antitumor prodrug monotherapy with prodrugs that are designed for direct recognition of tumor-associated factors, such as hypoxia, tumor-associated enzymes and receptors. Firstly, oxygen deficiency in the core of solid tumors leads to enhanced activity of reducing enzymes, like for example nitroreductases, which can be used for site- specific conversion of prodrug to drug. Secondly, some enzymes are present in elevated levels in tumor tissue: beta-glucuronidase leaks from necrotic areas within tumors, while tumor cells for invasive and metastatic activities need several tumor-associated proteases, like plasmin. These enzymes form an attractive target for designing selective prodrugs. Finally, tumor-selective expression of receptors can be exploited for the delivery of antitumor agents. Low molecular weight binding motifs for these receptors can be coupled to cytotoxic drugs in order to obtain tumor-homing conjugates. At present, receptor-binding motifs for a number of receptors that are required for angiogenesis are used for prodrug monotherapy. There exists an increasing body of literature, which describes the complex interplay not only between tumor-associated enzymes, but also between these enzymes and tumor-associated receptors in the process of tumor invasion and metastasis, indicating the feasibility of targeting cytotoxic drugs to these key players in tumor growth. This paper reviews the development and evaluation of anticancer prodrugs, and their application in the various prodrug monotherapy approaches.
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PMID:Anticancer prodrugs for application in monotherapy: targeting hypoxia, tumor-associated enzymes, and receptors. 1147 43

Uterine lavage fluids from postpartum and nonparturient mares were compared to determine when the normal secretory capacity of the postpartum uterus is restored. Lavage fluids were obtained from cyclic nonparturient mares on the second, fourth or fifth day of oestrus, and 3, 8, or 14 days after ovulation (seven mares/sampling day). Twelve intact postpartum mares were sampled 1 to 28 days postpartum (group A: 1, 6, 12 and 20; group B: 2, 8, 14 and 24; group C: 4, 10, 16 and 28 days postpartum; four mares/group). Three ovariectomized (OVX) postpartum mares were sampled as mares in group C. Samples were analysed for neutrophils, bacteria, total protein concentration, proteolytic and antiproteolytic activities and for various lysosomal enzyme activities. In nonparturient mares, activities of acid phosphatase, beta-glucuronidase (B-Gase), and N-acetyl-beta-D-glucosaminidase (NAGase) in uterine lavage fluids were significantly higher in mid- and late-dioestrus than in mid- to late-oestrus (p < 0.05). Lysozyme concentration, trypsin-inhibitor capacity (TIC), and plasmin activity were below the detection limit in nonparturient mares. One to four days postpartum, total protein, acid phosphatase, B-Gase, and NAGase were high but declined rapidly thereafter. Lysozyme and plasmin activities were high 1 to 6 days postpartum. TIC peaked around day 6 postpartum. On day 16 postpartum, acid phosphatase, B-Gase, and NAGase, being progesterone-dependent, tended to be higher in intact mares than in OVX ones (p < 0.1). Total protein and lysozyme concentrations, TIC, and B-Gase (p < 0.01) and acid phosphatase (p < 0.05) activities were significantly higher in parturient mares during postpartum oestrus than in oestrous nonparturient mares. High total protein concentration and TIC, and detectable lysozyme and plasmin activities during postpartum oestrus were associated with uterine inflammation. During dioestrus, differences between postpartum and nonparturient mares were not statistically significant and suggested that the endometrium of postpartum mares had resumed its normal secretory capacity by this time.
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PMID:Proteins and enzymes in uterine lavage fluid of postpartum and nonparturient mares. 1235 77

Cancer chemotherapy is associated with severe side effects which may be reduced by selective liberation, at the tumour site, of a cytotoxic agent from a non-toxic prodrug. Several strategies are used to achieve the required selective activation: with enzymes which are present in higher concentration in, or close, to the tumour (beta-glucuronidase, plasmin), with enzymes covalently linked to a macromolecular carrier able to recognize antigen positive cancer cells (ADEPT: Antibody Directed Enzyme Prodrug Therapy) or with reductive processes which are favoured in an hypoxic environment. Most of the prodrugs include a linker (or spacer) between the trigger and the drug (or effector). The design of such linkers is crucial in order to achieve a fast drug liberation under physiological conditions. The linker groups may be classified in two categories based on elimination or cyclization processes. The advantages and the limitations of each strategy are discussed.
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PMID:Design of selectively activated anticancer prodrugs: elimination and cyclization strategies. 1267 42