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)

Polymethylmethacrylate (PMMA) is clinically employed in a wide range of orthopaedic procedures. The etiology of the inflammatory reaction of recipient tissues to PMMA remains unresolved. Classically, polymorphonuclear leukocytes (PMNs) release cytoplasmic lysosomal granules when exposed to a variety of proinflammatory stimuli. Such degranulation contributes, and partially defines, the local tissue reaction to this foreign material. In the present investigation, PMMA particles (50-60 nm) were mixed with human PMNs, and the amount of lactate dehydrogenase, lysozyme, and beta-glucuronidase released from the cells was quantitated. In all cases, a dose-dependent increase in degranulation followed the addition of increasing amounts of PMMA to the PMNs. In addition, the migration of PMNs was diminished in a dose-dependent manner with exposure to increasing amounts of the cement. These results suggested that PMMA stimulates the release of leukocyte lysosomal contents and alters the migration characteristics of these cells in a manner that is consistent with the local inflammatory reaction to this cement.
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PMID:Polymorphonuclear leukocyte degranulation with exposure to polymethylmethacrylate nanoparticles. 187 59

Bone resorption in a modified bone culture system, based on incubation of small fragments from neonatal mouse calvarial bones, has been studied. Four bone fragments were dissected out from each mouse calvaria and were thereafter cultured in CMRL 1066 medium in plastic multiwell dishes. Bone resorption was assessed by 45Ca release from prelabeled bones. The rate of bone resorption in response to parathyroid hormone (PTH) was less in the anterior part of the calvaria compared to the posterior part. After removing the anterior region, four parietal bone fragments that showed identical basal and PTH-stimulated release of 45Ca could be dissected out from each mouse. Excretion of lactate dehydrogenase and beta-glucuronidase was the same in bones cultured submerged or on grids. Uptake of [3H]thymidine in bones cultured submerged was 54% of [3H]thymidine uptake in bones cultured on grids. Dose-response curves, established by using parietal bone fragments, showed that the sensitivity and the magnitude of the increase in 45Ca release seen after stimulation with PTH, prostaglandin E2, and 1 alpha-hydroxyvitamin D3 were the same for bones cultured submerged or on grids. The 45Ca release in response to stimulation with PTH, prostaglandin E2, and 1 alpha-OHD3 was the same in calvarial fragments cultured submerged and those previously obtained with calvarial halves cultured on grids. Thus, even though the rate of DNA synthesis was slower in bones cultured submerged, the rate and the magnitude of resorption were the same in bones cultured on grids or submerged. These data show that it is possible to perform studies on bone resorption with small fragments of neonatal mouse parietal bones.
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PMID:In vitro studies on bone resorption in neonatal mouse calvariae using a modified dissection technique giving four samples of bone from each calvaria. 188 17

Biochemical mechanisms underlying acrylamide induced neurotoxicity were examined using an in vitro model consisting of sagittal slices of rat brain. Incubation of brain slices under oxygen in artificial cerebrospinal fluid containing acrylamide produced a dose and time dependent inhibition of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Lysosomal enzymes, acid phosphatase, N-acetyl glucosaminidase and beta-glucuronidase decreased in a similar manner, while no changes were observed in the activity of Na+K+ATPase, cytochrome c oxidase and lactate dehydrogenase. Incubation of slices with two structurally related compounds, acetamide (a non-neurotoxic amide) and methylene bis-acrylamide (a weak neurotoxin), indicated that acrylamide selectively inhibited GAPDH, enolase and N-acetyl glucosaminidase at low concentration; similar doses of acetamide and methylene bis-acrylamide did not have the same effect on brain slices. Incubation with acrylamide depleted glutathione levels in slices, and the addition of glutathione to the incubation medium prevented acrylamide induced inhibition of GAPDH and lysosomal enzymes. Time dependent inhibition of lysosomal enzymes was also observed in vivo, in the brain and sciatic nerve of rats following a single dose of acrylamide. These results demonstrate that both in vitro and in vivo, lysosomal enzymes are also inhibited following acrylamide exposure. The rat brain slice model exhibits both selectivity and sensitivity towards neurotoxicants and hence, may prove to be an useful in vitro model for the mechanistic evaluation of neurotoxicity.
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PMID:The use of rat brain slices as an in vitro model for mechanistic evaluation of neurotoxicity-studies with acrylamide. 195 83

This study determined the effect of blood leucocyte depletion on the early inflammatory response of the lung to alpha-quartz. F344/N rats were instilled intratracheally with either physiological saline or 2 or 5 mg of alpha-quartz suspended in saline. One day prior to the instillation, half of the rats received an ip injection of rabbit antiserum that had been raised against rat neutrophils. The other half of the rats received an ip injection of normal rabbit serum. One day after the instillation of saline or quartz, the animals were euthanized and observed for changes in blood cell numbers, lung histopathology, and bronchoalveolar lavage fluid (BALF) content of indicators of an inflammatory response and cytotoxicity. The rabbit antiserum depleted the blood of most white blood cells of all types. BALF fluid from saline-instilled animals did not differ between the white blood cell-depleted and the nondepleted animals except for a 20% reduction in numbers of alveolar macrophages in the depleted animals. BALF fluid from the nondepleted, quartz-instilled animals had a dose-dependent increase in content of neutrophils and protein (indicator of an increase in the permeability of the alveolar/capillary barrier) as well as an increase in lactate dehydrogenase and glutathione reductase (cytoplasmic enzymes whose presence extracellularly indicates cytotoxicity), alkaline phosphatase (indicator of type II cell secretory activity), beta-glucuronidase, and acid proteinase (lysosomal enzymes) activities. The higher dose of quartz also elicited an increase in LTB4 and PGE2 content of BALF. GSH content of BALF was decreased by the quartz exposure. The depletion of blood white blood cells prevented the influx of neutrophils into the alveoli of the quartz-exposed rats and decreased the BALF markers of capillary permeability and cytotoxicity (protein content and extracellular cytoplasmic enzymes). The absence of neutrophils in the alveoli had no effect on the lysosomal content of BALF, indicating that the neutrophils were not the source of these enzymes in nondepleted rats exposed to alpha-quartz. The quartz-induced elevation of LTB4 in BALF was not observed in depleted rats, suggesting that neutrophils may be the source of the increase in this leukotriene in the BALF. Both the GSH content and the alkaline phosphatase activity in BALF were enhanced in the absence of alveolar neutrophils. The enhancement of GSH in BALF is consistent with the neutrophils being the source of reactive oxygen species that deplete GSH. The increased alkaline phosphatase activity in the BALF of both the depleted and nondepleted animals is consistent with the type II cell hypertrophy that was induced by quartz instillation and was neutrophil independent.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of blood leucocyte depletion on the inflammatory response of the lung to quartz. 203 43

The mean values of body mass index, haemoglobin A1, serum protein, total lipids, triglycerides, lactate dehydrogenase, alkaline phosphatase, amylase and beta-glucuronidase and heart rate and blood pressure and blood urea levels of Libyan diabetic patients with secondary complications are significantly higher than those of the patients without secondary complications. However, the mean values of fasting blood glucose, serum cholesterol and beta-N-acetylglucosaminidase of patients without complications are higher than those of the patients with secondary complications. The duration of diabetes in patients with secondary complications was 10.2 +/- 1 years while that of patients without complications was 5.2 +/- 0.65 years. The significance of these results is discussed.
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PMID:Secondary diabetic complications and biochemical parameters. 209 82

Thermal decomposition products of some perfluorinated polymers are toxic to experimental animals in small-scale combustion toxicity tests; the toxicity is dependent upon the heating procedure, combustion temperature, and other experimental conditions. In the current studies we investigated the time course of fume generation and exposure on pulmonary effects in rats following a 30-min exposure to perfluoropolymer decomposition products (i.e., fume concentration = 0.2 mg/m3 of tetrafluoroethylene/hexafluoropropylene copolymer (FEP)) pyrolyzed with either static or dynamic airflows. In the first set of experiments, five different groups of rats were exposed to FEP fumes in a static combustion toxicity test system. Three groups were exposed to unfiltered FEP fumes during 0- to 15-, 15- to 30-, and 0- to 30-min intervals, respectively, and one to a filtered (particle-free) atmosphere of combusted FEP for 30 min. Sham-exposed rats constituted the control group. Immediately after exposure, the rats were sacrificed and their lungs weighed and lavaged or perfused to assess indices of cytotoxicity. Our results showed that lung weights, markers of inflammation, and pulmonary hemorrhage and alkaline phosphatase, beta-glucuronidase, lactate dehydrogenase, and protein levels in bronchoalveolar lavage fluids were significantly elevated in all unfiltered FEP-exposed groups compared to those in either the rates exposed through filters or controls (P less than 0.01). In a second set of experiments using a dynamic pyrolysis toxicity test system, rats were exposed for 30 min to FEP-pyrolyzed fumes which were either freshly generated or aged for 1 or 5 min prior to delivery to the animal's breathing zone. Subsequently, lung cytotoxicity parameters were measured. Rats exposed directly to the fresh fumes demonstrated toxic effects consistent with those described above (P less than 0.01), but the pulmonary toxicity of aged (i.e., 1 or 5 min delay) FEP fumes was diminished in a time-dependent manner, suggesting that the toxicant was unstable. Histopathological studies correlated with biochemical results and revealed that inhalation of unfiltered or freshly generated FEP fumes produced a severe lung injury characterized by the development of alveolar and interstitial edema, intraalveolar hemorrhage, congestion, and fibrin deposition. Electron microscopy studies demonstrated severe damage to terminal bronchiolar cells and detachment of Type I epithelial and endothelial cells in pulmonary regions. The severity of pathology observed in lungs of rats exposed to 1-min aged fumes was intermediate between unfiltered/unaltered fume-exposed animals and sham controls. The results of these studies demonstrate that the lung toxicity of perfluoropolymer fumes is associated with the aerosol phase generated in perfluoropolymer pyrolysis.
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PMID:Attenuation of perfluoropolymer fume pulmonary toxicity: effect of filters, combustion method, and aerosol age. 211 7

Analysis of bronchoalveolar lavage fluid (BALF) appears to be a sensitive approach to characterizing an acute inflammatory response within the lung. More work, however, is needed to determine if analyses of BALF endpoints can predict chronic responses (i.e., fibrosis). The objective of the present study was to compare the dose and temporal pulmonary response of a known fibrogenic agent, silica, and two known nonfibrogenic agents, aluminum oxide and titanium dioxide. Animals were instilled with silica (0, 0.2, 1.0, or 5.0 mg/100 g body wt), titanium dioxide (1.0 or 5 mg/100 g body wt), aluminium oxide (1.0 or 5.0 mg/100 g body wt) or saline. Animals (n = 5/group) were terminated 1, 7, 14, 28, and 63 days following instillation, and the BALF was characterized by biochemical and cellular assays. Histopathological changes were determined at 60 days after exposure. The biochemical results demonstrated BALF levels of lactate dehydrogenase (LDH), beta-glucuronidase (BG), N-acetylglucosaminidase (NAG), and total protein (TP) increased in a dose-related fashion at the earlier time points for all test materials, with the magnitude of change being greatest for silica. The temporal response for these parameters was significantly different for the two classes of materials. With time, the response for the fibrogenic dust steadily increased, while the levels for the nonfibrogenic dusts decreased toward normal values during the 2-month study period. Of the cellular changes, total cell numbers, neutrophils, and lymphocyte numbers were the most sensitive markers of the pulmonary response. As shown with the biochemical parameters, the cellular response to silica increased with time while that of the nuisance dusts did not. It was also found that, similar to inhalation studies, high doses of a nuisance dust may result in toxicity/inflammation. This toxicity at high dose levels emphasizes the importance of choosing relevant doses when comparing potentially fibrogenic and nonfibrogenic dusts. In conclusion, the persistent and progressive changes seen in the biochemical (LDH, TP, BG, NAG) and cellular parameters (total cells, neutrophils and lymphocytes) following silica administration correlated with the fibrotic response which occurred after exposure to this material. The less dramatic and transient changes seen with aluminum oxide and titanium dioxide correlated with the inert nature of these nuisance dusts. The results of this study indicate evaluation of BALF may provide a means to predict the chronic pulmonary response to a material.
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PMID:The comparison of a fibrogenic and two nonfibrogenic dusts by bronchoalveolar lavage. 215 66

Studies in rats indicate that neutrophils (polymorphonuclear leukocytes (PMNs] are associated with areas of tissue damage after treatment with the hepatotoxicant, alpha-naphthylisothiocyanate (ANIT). Several synthetic and naturally occurring substances stimulate PMNs to release cytotoxic mediators, such as superoxide (O2-). The purpose of the present study was to test the hypothesis that ANIT stimulates the release of O2- from isolated rat PMNs. PMNs derived from rat peritoneum were treated with ANIT in vitro and tested for release of O2-. ANIT caused the release of O2- from PMNs in a concentration-dependent manner. Maximal O2- release (10 +/- 1 nmoles/30 minutes/2 x 10(6) cells) was achieved by an ANIT concentration of 110 microM. This ANIT-induced O2- release was significantly reduced or blocked completely by preincubation of PMNs for 10 minutes with 10 microM or 100 microM SKF 525A, respectively. The beta-isomer of ANIT, which does not cause cholestasis in vivo, did not stimulate O2- release. ANIT-stimulated O2- production decreased sharply after 5 minutes of incubation with ANIT and ceased entirely between 10 to 15 minutes. Shortly after this decrease in O2- production was an increase in the extracellular activity of lactate dehydrogenase. PMNs exposed to ANIT also failed to exclude trypan blue dye, either in the presence or in the absence of superoxide dismutase and catalase, suggesting a direct, oxygen radical-independent, cytotoxic effect of ANIT on PMNs. Release of the lysosomal enzyme, beta-glucuronidase, occurred within 5 minutes of incubation of isolated PMNs with ANIT (110 microM). These results indicate that exposure of rat PMNs to the hepatotoxicant, ANIT, causes the release of cytotoxic agents, whereas its less hepatotoxic beta-isomer does not.
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PMID:The cholestatic agent, alpha-naphthylisothiocyanate, stimulates superoxide release by rat neutrophils in vitro. 216 98

Eosinophil granule major basic protein (MBP) and neutrophils have each been implicated in the inflammatory late phase events of allergic disease. Based on this association and flow cytometric evidence presented in this report for MBP binding to neutrophils, we examined the ability of MBP to activate human neutrophils. Incubation of neutrophils with 0.5 to 3.0 microM MBP at room temperature produced a concentration-dependent chemiluminescence (CL) response that peaked after 50 to 70 min. Reduced-and-alkylated MBP, eosinophil cationic protein, and eosinophil-derived neurotoxin did not induce CL. MBP-induced CL was abrogated in the absence of Ca2+ and was absent in neutrophils isolated from two individuals with chronic granulomatous disease. MBP also stimulated release of superoxide anion (O2-) and lysozyme but not beta-glucuronidase or lactate dehydrogenase. Additionally, 1.5 microM MBP in combination with FMLP or platelet-activating factor stimulated a synergistic increase in O2- release from cytochalasin B-treated neutrophils. The degree of synergism with FMLP or platelet-activating factor was inversely related (p less than 0.005) to the level of MBP-induced O2- release. These results indicate that MBP activates neutrophils in a noncytolytic fashion and provide evidence that eosinophil-neutrophil collaboration may contribute to the pathogenesis observed in allergic late phase reactions.
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PMID:Noncytotoxic activation of neutrophils by eosinophil granule major basic protein. Effect on superoxide anion generation and lysosomal enzyme release. 217 May 21

The possible sources of biochemical changes in the lung, including changes in activities of lactate dehydrogenase (LDH), beta-glucuronidase (beta-GLU), choline kinase (CHK), and protease inhibitor (PI), as well as protein content, were evaluated following exposure to NO2. Hydroxyurea-induced granulocytopenia attenuated the LDH and beta-GLU responses (46% and 61%, respectively) following acute, but not subacute, exposure to NO2. Increases in PI activity and pulmonary protein content following exposure to NO2 were not altered by inhibition of protein synthesis by cycloheximide. The observed increase in PI activity appears to result from an activation process, whereas a major source of increased pulmonary protein content following exposure appears to occur from leakage into the lung. The response of the lung to irritant insult is thus dynamic, and the contribution from various sources to the biochemical makeup of the lung following irritant insult may depend on the phase of the pulmonary response.
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PMID:Pharmacologic manipulation of the murine pulmonary biochemical response to NO2. 226 87


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