Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several sulfhydryl reactive compounds have previously been shown to influence aqueous humor outflow facility. The purpose of the current study was to investigate the effect of glutathione depletion on certain of these sulfhydryl actions. Enucleated calf, monkey, and human eyes were perfused via the anterior chamber by the constant pressure (15 mmHg) technique. In calf eyes, perfusion of 10 mM cysteamine produced a small (-23%, P = 0.03) decrease in outflow facility that was also observed after hyaluronidase pretreatment. In contrast, following pretreatment with 1 mM BCNU [1,3 bis(2 chlorethyl)-1-nitrosourea], an inhibitor of glutathione reductase, and 10 mM diamide, a glutathione oxidant, which did not by themselves significantly affect outflow facility, perfusion of cysteamine resulted in an opposite effect--a remarkably large (+90%, P less than 0.001) increase in outflow facility. Other reduced and oxidized sulfhydryl-containing compounds such as cysteine, beta-mercaptoethanol, and glutathione, itself, as well as the non-sulfhydryl reducing agent, ascorbic acid, were substituted for cysteamine in this protocol and found to produce similar effects of varying magnitudes. In general, the reduced sulfhydryl containing compounds and ascorbic acid were the most effective. Pretreatment with BCNU alone without diamide did not produce this effect. Treatment with BCNU and diamide resulted in a greater than 75% decrease in reduced glutathione levels and a concomitant tenfold increase in glutathione mixed disulfide levels (0.229 vs. 0.030 mumol g-1 wet weight) in the calf trabecular meshwork. The subsequent perfusion with cysteamine reversed this mixed disulfide formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influences of glutathione and sulfhydryl containing compounds on aqueous humor outflow function. 216 47

Several different strategies to improve the in vitro cytocidal effect of 5-fluorouracil/leucovorin (5FU/LV), including modulation of dosage and schedule and combination with other cytotoxic agents or biochemical modulators, were examined in the COLO 320DM and Ht-29 cell lines by means of the Bactec system. Modest enhancement of 5FU activity by coadministration of LV was observed in both human colon cancer cell lines. Neither increased concentrations of LV nor prolonged drug exposure or preincubation with LV were found to enhance significantly the growth inhibitory activity of combined 5FU/LV. The only parameter that was found to affect the killing potential of the combination was the concentration of 5-FU, suggesting that lower doses of the antimetabolite would be more effective (COLO 320DM: P less than 0.003; Ht-29 P less than 0.02). The addition of either cisplatin, hyaluronidase or dipyridamole to 5-FU/LV yielded synergistic growth inhibition in 3/6, 2/6 and 2/6 human colon cancer cell lines, respectively. Strictly additive effects were noted for the combination with BCNU as well as concurrent exposure of the cells to 42 degrees C hyperthermia. Whether or not certain combined 5FU/LV drug regimens will result in an improved therapeutic index, however, remains to be determined in properly designed clinical trials.
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PMID:A study of various strategies to enhance the cytotoxic activity of 5-fluorouracil/leucovorin in human colorectal cancer cell lines. 262 28