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:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This investigation studied the effects of a shift from a mixed diet to a lactovegetarian diet on some cancer-associated bacterial enzymes in human feces (beta-glucuronidase, beta-glucosidase, and sulphatase). Three months after the shift to the lactovegetarian diet, there was a significant decrease in beta-glucuronidase, beta-glucosidase, and sulphatase activities per gram feces wet weight (p less than 0.05, less than 0.05, and less than 0.001, respectively). In contrast, glucuronide and glucoside hydrolysis remained unchanged per gram dry weight, although sulphatase activity was still significantly lowered when expressed this way (p less than 0.01). However, the fecal excretion increased significantly (p less than 0.05). Part of the explanation for the decreased enzyme activities is obviously a dilution effect, because much of the increased fecal weight after the shift in diet was associated with a higher water content. The higher water content was probably due to a higher fiber intake (p less than 0.001). Thus, the results in this paper indicate that a change from a mixed diet to a lactovegetarian diet leads to a decrease in certain enzyme activities proposed to be risk factors for colon cancer.
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PMID:Shift from a mixed diet to a lactovegetarian diet: influence on some cancer-associated intestinal bacterial enzyme activities. 212 19

Implanted foreign bodies are highly susceptible to pyogenic infections and represent a major problem in modern medicine. In an effort to understand the pathogenesis of these infections, we studied the phagocytic function in the vicinity of a foreign body by using a recently developed guinea pig model of Teflon tissue cages subcutaneously implanted (Zimmerli, W., F.A. Waldvogel, P. Vaudaux, and U.E. Nydegger, 1982, J. Infect. Dis., 146:487-497). Polymorphonuclear leukocytes (PMN) purified from tissue cage fluid had poor bactericidal activity against a catalase-positive microorganism. When compared with blood or exudate PMN, they exhibited a significant reduction in their ability to generate superoxide in response to a particulate or a soluble stimulus (72 and 57%, respectively, P less than 0.001). Not only their total contents in myeloperoxidase, beta-glucuronidase, lysozyme, and B12 binding protein were significantly reduced (by 62, 21, 47, and 63%, respectively, P less than 0.01), but also their capability for further secretion of residual B12 binding protein upon stimulation. Ingestion rates of endotoxin-coated opsonized oil particles were reduced by 25% (P less than 0.05). In an effort to reproduce these abnormalities in vitro, fresh peritoneal exudate PMN were incubated with Teflon fibers in the presence of plasma. Interaction of PMN with the fibers led to significant increases in hexose monophosphate shunt activity and exocytosis of secondary granules (P less than 0.01). PMN eluted after such interaction showed defective bactericidal activity, oxidative metabolism, and granular enzyme content similar to those observed in tissue cage PMN. The local injection of fresh blood PMN into tissue cages at the time of, or 3 h after, inoculation with 100 microorganisms (Staphylococcus aureus Wood 46) reduced the infection rate from 50 to 56 cages to 1 of 21 (P less than 0.001) and 3 of 8 cages (P less than 0.001), respectively. These results suggest that the in vivo as well as in vitro interaction of PMN with a nonphagocytosable foreign body induces a complex PMN defect, which may be partly responsible for the high susceptibility to infection of foreign bodies.
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PMID:Pathogenesis of foreign body infection. Evidence for a local granulocyte defect. 632 36

Pharmacokinetic and pharmacodynamic variables of flunixin were studied in calves after IV administration of the drug at a dose rate of 2.2 mg/kg of body weight. The anti-inflammatory properties of flunixin were investigated, using a model of acute inflammation; this involved surgically implanting tissue cages at subcutaneous sites and stimulating the tissue cage granulation tissue by intracavitary injection of carrageenan. The actions of flunixin on exudate concentrations of several substances related to the inflammatory process, including proteases (metalloprotease [active and total] and cysteine and serine proteases), enzymes (lactate dehydrogenase, acid phosphatase, and beta-glucuronidase [beta-glu]), eicosanoid (prostaglandin E2 [PGE2], leukotriene B4, and serum thromboxane B2 [TXB2]) concentrations, and bradykinin (BK)-induced edema, were investigated. Flunixin had a long elimination half-life--6.87 +/- 0.49 hours--and volume of distribution was 2.11 +/- 0.37 L/kg, indicating extensive distribution of the drug in the body. Body clearance was 0.20 +/- 0.03 L/kg/h. Flunixin exerted inhibitory effects on serum TXB2 and exudate PGE2 concentrations, beta-glu activity, and BK-induced swelling. Other enzymes and inflammatory mediators were not significantly affected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Determination of pharmacokinetics and pharmacodynamics of flunixin in calves by use of pharmacokinetic/pharmacodynamic modeling. 765 89

Pharmacokinetic and pharmacodynamic parameters were established for enantiomers of the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (KTP), each administered separately at a dose level of 1.1 mg/kg to a group of six New Forest geldings, in a three-period cross-over study using a tissue cage model of inflammation. For both S(+)-and R(-)-KTP, penetration into tissue cage fluid (transudate) and inflamed tissue cage fluid (exudate) was rapid, and clearances from exudate and transudate were much slower than from plasma. AUC values were, therefore, higher for exudate and, to a lesser degree, transudate than for plasma. Unidirectional chiral inversion of R(-)-to S(+)-KTP was demonstrated. Administration of both enantiomers produced marked, time-dependent inhibition of synthesis of serum thromboxane B2 and exudate prostaglandin E2, indicating non-selective inhibition of cyclo-oxygenase (COX) isoenzymes COX-1 and COX-2 respectively. Administration of both enantiomers also produced partial inhibition of beta-glucuronidase release into inflammatory exudate and of bradykinin-induced skin oedema. It is suggested that, although S(+)-KTP is generally regarded as the eutomer, R(-)-KTP was probably at least as active in inhibiting bradykinin swelling. Pharmacokinetic/pharmacodynamic (PK/PD) modelling of the data could not be undertaken following R(-)-KTP administration because of chiral inversion to S(+)-KTP, but pharmacodynamic parameters, Emax, EC50, N, keO and t1/2(keO). were determined for s(+)-KTP using the sigmoidal Emax equation. PK/DP modelling provided a novel means of comparing and quantifying several biological effects of KTP and of investigating its mechanisms of action.
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PMID:Pharmacokinetics and pharmacodynamics of ketoprofen enantiomers in the horse. 897 76

We studied the effects of voluntary exercise on nonspecific immunological mechanisms in mice. In this study, 7 week old male ICR mice were divided into two groups: a non-exercise group (control) and a group given voluntary exercise (Vex group). Each mouse of the Vex group was kept in an individual cage equipped with a voluntarily revolving wheel that the mouse had free access to. The duration of voluntary exercise was 3 days per week for 8 weeks. The following results were obtained: 1) After 8 weeks of voluntary exercise, food consumption, the weight of the anterior tibialis muscle and succinate dehydrogenase activity in the anterior tibialis muscle increased significantly in the Vex group compared to the control group. 2) By means of the carbon clearance method, phagocytosis of the reticuloendothelial system was increased in the Vex group. 3) Glucose consumption capacity and O-2 production capacity of peritoneal macrophages (M phi) were significantly increased in the Vex group compared to the control group. 4) The acid phosphatase (APH), beta-glucuronidase (GLU) and lactate dehydrogenase (LDH) activities of peritoneal M phi increased significantly in the Vex group. 5) Concanavalin A (Con A)-induced cell proliferation in the spleen was high in the Vex group. Based on the above findings, it may be surmised that voluntary exercise enhances nonspecific immunological mechanisms and thereby improves the host defense mechanisms in mice.
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PMID:[Effects of voluntary exercise on nonspecific immunological mechanisms in mice]. 910 77

This investigation studied the effects of a shift from a well-balanced mixed diet to a lacto-vegetarian diet on the mutagenic activity in urine and feces and on some cancer-associated bacterial enzymes in human feces (beta-glucuronidase, beta-glucosidase, and sulphatase). Three months after the shift to the lacto-vegetarian diet, there was a significant decrease in mutagenic activity in urine and feces, beta-glucuronidase, beta-glucosidase, and sulphatase per gram feces wet weight. In contrast, the fecal mutagenic activity and the enzyme activities remained unchanged if expressed per daily output. However, the urinary mutagenic activity expressed as total daily output decreased. Part of the explanation for the decreased fecal mutagenic activity and the decreased enzyme activities is obviously a dilution effect, because much of the increased fecal weight after the shift in diet was associated with a higher water content.
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PMID:Dietary influence on some proposed risk factors for colon cancer: fecal and urinary mutagenic activity and the activity of some intestinal bacterial enzymes. 916 43

Carprofen is a nonsteroidal anti-inflammatory drug of the 2-arylpropionate subclass. It contains a single chiral centre and exists in two enantiomeric forms. In this study rac-carprofen, at two dosages, 0.7 and 4.0 mg/kg, and placebo were administered i.v. to six New Forest horses in a three period cross-over study. The concentration-time profiles were established for R(-) and S(+)-carprofen for plasma and both inflamed (exudate) and noninflamed (transudate) tissue cage fluids. R(-)-carprofen was the predominant enantiomer in all three fluids, as indicated by plasma area under the curve (AUC) values for R(-) and S(+)-carprofen of 117.4 and 22.6 microg h/mL (low dose carprofen) and 557.5 and 138.1 microg h/mL (high dose carprofen) respectively. Penetration of both enantiomers into exudate was slow and limited and passage into transudate was even lower. The pharmacodynamics of rac-carprofen was investigated at both the molecular level and in terms of the ability to suppress components of the tissue cage inflammatory response. Low dose carprofen produced only moderate and transient inhibition of serum thromboxane (Tx)B2 but failed to affect exudate prostaglandin (PG)E2 concentrations, whilst suppression of exudate leukotriene (LT)B4 and beta-glucuronidase was not significant. High dose carprofen produced greater and more persistent inhibition of serum TxB2 and virtually abolished exudate PGE2 synthesis. Some inhibition of LTB4 and beta-glucuronidase in exudate was also obtained. At both dosages rac-carprofen reduced the swelling produced by intradermal bradykinin injection but only high dose carprofen was anti-inflammatory as indicated by suppression of temperature rise over exudate tissue cages and neither dose affected leucocyte numbers in exudate. When considered in conjunction with previous data on carprofen, the present findings indicate that carprofen is not a selective inhibitor of cyclooxygenase (COX) isoenzymes, COX-1 and COX-2 in the horse, although it may show some preference for COX-2 inhibition. Because low dose carprofen, which is the clinically recommended dosage, produces minimal inhibition of COX, it is likely to achieve its therapeutic effects at least partially through other pathways, possibly including weak to moderate inhibition of 5-lipoxygenase and of enzyme release. The good safety margin of carprofen in clinical use might also be explained by weak COX inhibition and by other actions at the molecular level.
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PMID:Pharmacodynamics and enantioselective pharmacokinetics of racemic carprofen in the horse. 1248 49

Rutaecarpine is an alkaloid isolated from the medicinal herb Evodia rutaecarpa. This study was to evaluate the elimination pathway of rutaecarpine in rat feces and urine. Rutaecarpine and its metabolites (3-, 10-, 11- and 12-hydroxyrutaecarpine) in urine were measured after incubation with beta-glucuronidase. After the rutaecarpine was administered (25 and 100 mg/kg) orally to rats, the urine and fecal samples were collected using a metabolic cage for five consecutive days. For determining rutaecarpine, the mobile phase consisted of acetontrile-10 mM NaH(2)PO(4) (60:40, v/v, pH 4.2 adjusted with orthophosphoric acid) with a flow rate of 1 mL/min. The calibration curve was linear in concentrations of 0.05-50 microg/mL in fecal and urine sample. The results indicated that more than 42% of the rutaecarpine was excreted by feces after oral administration (25 and 100 mg/kg), but only a small amount of rutaecarpine was detected in urine at a higher dose of rutaecarpine (100 mg/kg). After incubation with beta-glucuronidase, the hydroxyrutaecarpine in urine was eluted using methanol-acetonitrile-0.04% formic acid (6:30:64, v/v) with a flow rate of 1.2 mL/min. We conclude that the metabolic pathway of rutaecarpine went through phase I hydroxylation and phase II conjugation, and the major metabolite is 10-hydroxyrutaecarpine eliminated from urine of the rat.
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PMID:Elimination of rutaecarpine and its metabolites in rat feces and urine measured by liquid chromatography. 1679 25

Diet-induced changes in the activities of bacterial enzymes are known to play a role in colon cancer development. Resveratrol has been implicated as a protective agent in carcinogenesis. In the present study, the effect of resveratrol on the activities of faecal and colonic biotransforming enzymes such as beta-glucuronidase, beta-glucosidase, beta-galactosidase, mucinase, nitroreductase and faecal sulfatase activity was assessed. The total number of aberrant crypt foci and their distribution in the proximal, medial and distal colon were observed in 1,2-dimethylhydrazine (DMH)-induced rats (group 3) and other treatment groups (groups 4-6). DMH (0.02 g/kg body weight) was given subcutaneously once a week for 15 consecutive weeks, and the experiment was terminated at 30 weeks. DMH-treated rats showed elevated levels of cancer-associated bacterial enzyme activities, whereas on resveratrol supplementation in three different regimens, rats showed lowered activities. Resveratrol supplementation throughout the experimental period (group 6) exerted a more pronounced effect (P < 0.01) by modulating the development of aberrant crypt foci and the activities of bacterial enzymes than did the other treatment regimens (groups 4 and 5). Thus, the present results demonstrate the inhibitory effect of resveratrol on DMH-induced colon carcinogenesis in rats.
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PMID:Dietary supplementation of resveratrol suppresses colonic tumour incidence in 1,2-dimethylhydrazine-treated rats by modulating biotransforming enzymes and aberrant crypt foci development. 1687 3

Development of nonimmunogenic and specific reporter genes to monitor gene expression in vivo is important for the optimization of gene therapy protocols. We developed a membrane-anchored form of mouse beta-glucuronidase (mbetaG) as a reporter gene to hydrolyze a nonfluorescent glucuronide probe (fluorescein di-beta-D-glucuronide, (FDGlcU) to a highly fluorescent reporter to assess the location and persistence of gene expression. A functional beta-glucuronidase (betaG) was stably expressed on the surface of murine CT26 colon adenocarcinoma cells where it selectively hydrolyzed the cell-impermeable FDGlcU probe. FDGlcU was also preferentially converted to fluorescent probe by (betaG) on CT26 tumors. The fluorescent intensity in betaG-expressing CT26 tumors was 240 times greater than the intensity in control tumors. Selective imaging of gene expression was also observed after intratumoral injection of adenoviral betaG vector into carcinoma xenografts. Importantly, mbetaG did not induce an antibody response after hydrodynamic plasmid immunization of Balb/c mice, indicating that the reporter gene product displayed low immunogenicity. A membrane-anchored form of human betaG also allowed in vivo imaging, demonstrating that human betaG can be employed for imaging. This imaging system therefore, displays good selectivity with low immunogenicity and may help assess the location, magnitude and duration of gene expression in living animals and humans.
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PMID:Gene expression imaging by enzymatic catalysis of a fluorescent probe via membrane-anchored beta-glucuronidase. 1723 92


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