Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.17 (PCE)
 1,301 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Physiologically based pharmacokinetic (PBPK) models describing the uptake, metabolism, and excretion of xenobiotic compounds are now proposed for use in regulatory health-risk assessments. In this study we investigate the extent of PCE metabolism arising from domestic respiratory exposure to tetrachloroethylene (PCE) from ground water, as predicted using a PBPK model. Indoor exposure patterns we use as input to the PBPK model are realistic ones generated from a three-compartment model describing volatilization of PCE from domestic water into household air. Values we use for the metabolic parameters of the PBPK model are estimated from data on urinary metabolites in workers exposed to PCE. It is shown that for respiratory PCE exposure due to typical levels of PCE in ground water, use of time-weighted average air concentrations with a steady-state PBPK model yields estimates of total metabolized PCE similar to those obtained using completely dynamic modeling, despite considerable uncertainty in key exposure- and metabolic-model parameters. These findings suggest that, for PCE, risk estimation taking pharmacokinetics into account may be accomplished using a simple analytic approach.
 ...
PMID:Linking indoor air and pharmacokinetic models to assess tetrachloroethylene risk. 324 58

One hundred and eighty-nine adults with acute pharyngitis had culture and serological evaluation for group A beta haemolytic streptococci (GABHS), Mycoplasma pneumoniae, and Branhamella catarrhalis. Sixteen patients had evidence for infection with GABHS, none for M. pneumoniae, and one for B. catarrhalis. For those with GABHS, there was no significant difference between empirical treatment by erythromycin or amoxicillin. For those without GABHS, empirical treatment with erythromycin appeared to result in a statistically significant reduction in cough and a noticeable but less than significant reduction of other symptoms when compared to empirical treatment with amoxicillin. The new formulation of erythromycin utilized in this study (PCE) may be associated with a reduction in gastrointestinal intolerance from that reported with other erythromycin products.
 ...
PMID:Aetiology of acute pharyngitis and clinical response to empirical therapy with erythromycin versus amoxicillin. 329 74

A 1-cm2 area on the back of CD1 mice was prepared for topical application of minoxidil, N-methyl-N-nitrosourea (MNU), or cyclophosphamide (CY) by clipping or plucking hair from a patch of skin. Plucking stimulates hair follicle cell division while clipping does not. Minoxidil was topically administered for 8 consecutive days. CY or MNU was administered topically once on the eighth day postplucking. The incidence of nuclear aberrations and mitotic figures were measured in hair follicles while frequency of micronuclei and the ratio of RBC/PCE were measured in the bone marrow. Results with minoxidil showed no increase in either nuclear aberrations in the hair follicle or micronuclei in the bone marrow. These results suggest that topically applied minoxidil is not genotoxic. In contrast, a dose-dependent effect of MNU on the incidence of nuclear aberrations in the hair follicle was seen. CY induced a dose-dependent increase in the incidence of micronuclei in the bone marrow and in nuclear aberrations in the hair follicle after topical application. Minoxidil applied to clipped mice significantly increased the incidence of mitotic figures above that seen in both the clipped and plucked controls. This suggests that minoxidil is a mitogenic agent in the hair follicle. These findings are consistent with the success of topically applied minoxidil in the treatment of alopecia areata.
 ...
PMID:Nongenotoxicity of minoxidil in murine hair follicles as determined by the nuclear aberration assay. 334 Oct 23

The ability of methyl isocyanate (MIC) to induce mutagenic and cytotoxic effects in vivo in the mouse micronucleus test was evaluated by assessing the induction of micronuclei and depression of polychromatic erythrocytes in bone marrow and peripheral blood smears. Animals were exposed to MIC through intraperitoneal injection for 2 and 5 days in separate experiments, and bone marrow and peripheral blood were sampled 6 and 48 h after the last injection, respectively. MIC did not significantly increase the frequencies of micronucleated polychromatic erythrocytes (MN-PCE) and micronucleated normochromatic erythrocytes (MN-NCE) in bone marrow and peripheral blood samples respectively in either twice or multiply treated mice. However, a dose-dependent depression in percentage PCE observed was significant. This indicates that MIC exposure led to the cytotoxic effect by inhibition of bone marrow cell proliferation.
 ...
PMID:Cytogenetic activity of methyl isocyanate in vivo in the mouse micronucleus test. 338 49

In a companion paper (Luke et al., 1988), the effect of exposure duration and regimen on benzene induced-bone marrow damage was evaluated in male and female DBA/2 mice using the peripheral blood micronucleus assay. To assess the general applicability of the findings obtained for DBA/2 mice to other strains, similar studies were conducted using B6C3F1 and C57B1/6 male mice. An analysis of peripheral blood smears taken weekly from these mice exposed to 300 ppm benzene for 13 weeks (6 h per day) for either 5 days per week (Regimen 1) or for 3 days per week (Regimen 2) revealed: (i) a highly significant increase in the frequency of micronucleated polychromatic erythrocytes (MN-PCE), the magnitude of which was strain specific (DBA/2 greater than C57B1/6 = B6C3F1), but independent of exposure regimen and, except for Regimen 2 B6C3F1 mice, of exposure duration. In male B6C3F1 mice, MN-PCE frequencies increased slightly with increasing exposure duration; (ii) a strain- (C57B1/6 = B6C3F1 greater than DBA/2) and regimen- (Regimen 1 greater than Regimen 2) dependent increase across time in the frequency of micronucleated normochromatic erythrocytes (MN-NCE). Apparent steady-state conditions for MN-NCE frequencies were attained by about 5 weeks of exposure in male mice of all three strains exposed to benzene by Regimen 2. Steady-state conditions for MN-NCE frequencies in male mice exposed to benzene by Regimen 1 did not occur during the duration of the study, with strain-dependent differences in the kinetics of MN-NCE accumulation being present; and (iii) in all 3 strains, an initial severe depression in the rate of erythropoiesis, the return of which to normal levels was both strain- (C57B1/6 = B6C3F1 greater than DBA/2) and regimen- (Regimen 1 greater than Regimen 2) dependent. These data indicate that the induction of genotoxic and cytotoxic damage in the bone marrow of male mice exposed to benzene for 13 weeks can be highly dependent on strain, exposure regimen and exposure duration but that under no circumstance did the level of genotoxic damage induced by benzene decrease under multiple exposure conditions.
 ...
PMID:The effect of exposure regimen and duration on benzene-induced bone marrow damage in mice. II. Strain comparisons involving B6C3F1, C57B1/6 and DBA/2 male mice. 340 36

The interactions of the hallucinogenic drug PCP [1-(1-phenylcyclohexyl)piperidine] and some of its analogs with the nicotinic acetylcholine receptor-ionic channel complex were studied using electrophysiological techniques. The peak amplitude and the decay time constant of the nerve-evoked end-plate current (EPCs) recorded from the frog sartorius muscle were reduced by all the analogs in a concentration-dependent manner (IC50 between 5 and 90 microM). PCP, TCP [1-[1-(2-thienyl)cyclohexyl]-piperidine] and PCE (N-ethyl-1-phenylcyclohexylamine), among other analogs, caused a negative slope conductance in the current-voltage relationship at hyperpolarized potentials and a voltage- and time-dependent depression of the peak amplitude of the EPC. When the piperidine ring of the PCP molecule was substituted by a morpholino ring, as in 1-(1-phenylcyclohexyl)morpholine and 1-[1-(2-thienyl)-cyclohexyl]morpholine, the potency decreased and the negative conductance was eliminated. The removal of the piperidine ring of PCP in 1-phenylcyclohexylamine and the hydroxylation of the cyclohexane ring in 4-phenyl-4-piperidino-cyclohexanol reduced the potency and produced double exponential decays at potentials between +50 and -50 mV. At -100 mV, the potency for decreasing peak EPC amplitude was well correlated with the potency for reducing the decay time constant for all the analogs. The voltage- and time-dependent depression of the EPC amplitude was reduced by substitution of a morpholino ring and by the elimination of the piperidine ring of PCP. The behaviorally active analogs were the most potent EPC blockers, which suggests a synaptic role for the production of depressant behavioral effects observed with PCP.
 ...
PMID:Effects of phencyclidine and its analogs on the end-plate current of the neuromuscular junction. 348 35

The genotoxic effect of whole tobacco smoke was studied employing the Salmonella/microsome mutagenicity assay, the micronucleus test in mouse bone marrow and UDS in peripheral human lymphocytes. It was established that tobacco smoke (120-480 cm3 in a 16-1 glass chamber, at 1-10 min exposure time) induced a 3-9-fold increase of spontaneous his+ reversion mutation rate in S. typhimurium TA98, but not in strains TA97a, TA100 and TA102. Addition of S9 mix obtained from the liver of Aroclor 1254-treated rats was necessary to reveal the mutagenic activity of tobacco smoke. Treatment of BDF1 mice placed in a 14-1 glass chamber with tobacco smoke (600 cm3 smoke, 2 exposures of 30 min each, with a 1-min interval between them) caused a 2-fold dose-dependent elevation of the number of micronucleated PCE in bone marrow. No cumulative effect was detected when mice were treated with tobacco smoke during 2-28 consecutive days. The effect observed 24 h after tobacco-smoke exposure was abolished 48 h later. Tobacco smoke (180 or 360 cm3) passed through the culture medium (with or without S9 mix) of human peripheral lymphocytes (the cells were then incubated for 60 min at 37 degrees C) did not increase the spontaneous rate of UDS. Both the Salmonella/microsome mutagenicity assay employing S. typhimurium TA98 strain and the micronucleus test in mouse bone marrow might be useful in studying tobacco smoke-induced mutagenesis.
 ...
PMID:Investigation of the mutagenic activity of tobacco smoke. 355 21

Groups of male B6C3F1 mice (N = 12) were exposed to ambient air or to gaseous 1,3-butadiene (BD) at 6.25, 62.5, and 625 ppm for 10 exposure days (6 hr + T90/day). Exposure to BD induced in bone marrow: 1) a significant increase in the frequency of chromosomal aberrations (CA); 2) a significant elevation in the frequency of sister chromatid exchanges (SCE); 3) a significant lengthening of the average generation time (AGT); 4) a significant depression in the mitotic index (MI); and, as measured in the peripheral blood, 5) a significant increase in the proportion of circulating polychromatic erythrocytes (%PCE), and 6) a significant increase in the level of micronucleated PCE (MN-PCE) and micronucleated normochromatic erythrocytes (MN-NCE). The most sensitive indicator of genotoxic damage was the frequency of SCE (significant at 6.25 ppm), followed by MN-PCE levels (significant at 62.5 ppm), and then by CA and MN-NCE frequencies (significant at 625 ppm). The most sensitive measure of cytotoxic damage was AGT (significant at 62.5 ppm), followed by %PCE (significant at 625 ppm), and then by MI (significant by trend test only). Because each cytogenetic endpoint was evaluated in every animal, a correlation analysis was conducted to evaluate the degree of concordance among the various indicators of genotoxic and cytotoxic damage. The extent of concordance ranged from a very good correlation between the induction of MN-PCE and the induction of SCE (correlation coefficient r = 0.9562) to the lack of a significant correlation between the depression in the MI and any other endpoint (r less than 0.37).
 ...
PMID:Comparative cytogenetic analysis of bone marrow damage induced in male B6C3F1 mice by multiple exposures to gaseous 1,3-butadiene. 356 68

The purpose of this study was to determine the influence of endurance-type exercise training on alterations of the ammonia content of blood in exercising humans. Seven females and four males trained 6 days/wk for 7 wk alternating days of continuous cycling (40 min) and interval running (five 5-min bouts). The NH3 content of blood was determined before and during cycle ergometer (CE) exercise (4 min) at power outputs (PO) of 119, 172, and 241 W pretraining and of 163, 230, and 271 W posttraining. These PO for each occasion represent relative work loads of approximately 65, 90, and 115% of peak CE maximum O2 uptake (PCE VO2), respectively. Training increased (P less than 0.05) PCE VO2 approximately 32% (2.72 +/- 0.25 to 3.56 +/- 0.29 l/min or 38.5 +/- 1.9 to 51.2 +/- 2.3 ml X kg-1 X min-1). Both pre- and posttraining the NH3 content of blood increased (P less than 0.05) with increasing intensity of exercise. Training did not influence the measure of these responses during exercise at the same relative intensity. During exercise at the same absolute PO, approximately 168 or 235 W, however, increases in blood NH3 were less (P less than 0.05) after training. The results indicate that the magnitude of increase in blood NH3 during exercise is determined by the energy requirement of the absolute work load, relative to an individual's aerobic power.
 ...
PMID:Endurance training reduces the magnitude of exercise-induced hyperammonemia in humans. 357 Oct 78

Tetrachloroethylene (PCE) and trichloroethylene (TCE), common industrial solvents, are among the most frequent contaminants found in groundwater supplies. Due to the potential toxicity and carcinogenicity of chlorinated ethylenes, knowledge about their transformation potential is important in evaluating their environmental fate. The results of this study confirm that PCE can be transformed by reductive dehalogenation to TCE, dichloroethylene, and vinyl chloride (VC) under anaerobic conditions. In addition, [14C]PCE was at least partially mineralized to CO2. Mineralization of 24% of the PCE occurred in a continuous-flow fixed-film methanogenic column with a liquid detention time of 4 days. TCE was the major intermediate formed, but traces of dichloroethylene isomers and VC were also found. In other column studies under a different set of methanogenic conditions, nearly quantitative conversion of PCE to VC was found. These studies clearly demonstrate that TCE and VC are major intermediates in PCE biotransformation under anaerobic conditions and suggest that potential exists for the complete mineralization of PCE to CO2 in soil and aquifer systems and in biological treatment processes.
 ...
PMID:Biotransformation of tetrachloroethylene to trichloroethylene, dichloroethylene, vinyl chloride, and carbon dioxide under methanogenic conditions. 392 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>