Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to compare the disposition and metabolism of [14C]1,2-dichloropropane [( 14C]DCP) following oral and inhalation exposure since these two routes are of interest with regards to occupational and accidental exposure. [14C]DCP was administered orally to groups of four rats of each sex as a single dose of 1 or 100 mg/kg and as a multiple 1 mg/kg nonradiolabeled dose for 7 days followed by a single 1 mg [14C]DCP/kg dose on day 8. In addition, four rats of each sex were exposed to [14C]DCP vapors for a 6-h period in a head-only inhalation chamber at target concentrations of 5, 50 and 100 ppm. [14C]DCP was readily absorbed, metabolized and excreted after oral or inhalation exposure. For all treatment groups the principal routes of elimination were via the urine (37-65%) and expired air (18-40%). The tissues, carcass, feces and cage wash contained less than 11, 9.7 and 3.8% of the dose, respectively. The major urinary metabolites, as a group, from the oral and inhalation exposures were identified as three N-acetylcysteine conjugates of DCP, N-acetyl-S-(2-hydroxypropyl)-L-cysteine, N-acetyl-S-(2-oxopropyl)-L-cysteine and N-acetyl-S-(1-carboxyethyl)-L-cysteine. The majority (61-87%) of the expired volatile organic material was found to be parent DCP in all samples analyzed. Increasing the dose/concentration of [14C]DCP resulted in an increase in the amount of exhaled [14C]-volatile organics. The peak DCP blood concentrations (inhalation exposure) were not proportional to dose, indicating a dose-dependency in the blood clearance of DCP. Nonetheless, upon termination of exposure, DCP was rapidly eliminated from the blood. In all treatment groups, following oral and inhalation exposure the majority of the radioactivity was eliminated by 24 h postdosing and no differences were noted between sexes. Therefore, it can be concluded that in the rat the pharmacokinetics and metabolism of [14C]DCP are similar regardless of route of exposure or sex.
 ...
PMID:Disposition and metabolism of [14C]1,2-dichloropropane following oral and inhalation exposure in Fischer 344 rats. 189

Fibrogenic effects of amorphous quartz dusts are discussed more and more during recent years. In order to study alterations due to amorphous silica (quartz glass VP 203-006) in comparison with crystalline quartz (DQ-12), an inhalation experiment in rats was carried out. Male Wistar rats were separated in two dust exposed groups (n = 35) and one control group (n = 30). The experiment was carried out in inhalation chambers with a slowly rotating animal cage for 12 months, 7 h per day, and 5 days per week. The dust concentration was 10 mg/m3. After 4 and after 8 months of inhalation, 5 animals of each group were sacrificed. After 12 months 15 rats of the dust exposed groups and 10 controls were euthanized. The remaining animals were kept for another 12 months post-inhalation period. Regarding the macroscopical appearance of the lungs, the relative organ weights and the histomorphological reaction pattern, marked dust depending differences are obvious. In the lungs of DQ-12-exposed animals diffuse structural changes occur, including fibrosis and severe reaction of macrophages. Histology of lungs from quartz glass exposed animals reveals only a slight and focally arranged cellular reaction with a few collagenous fibers. However, in both dust exposed groups the mediastinal lymph nodes are extremely enlarged with severe fibroses. Additionally, the following blood parameters were determined: lysozyme, ACE, GOT, GPT, and AP. The most pronounced changes are detectable in lysozyme and GOT after DQ-12 exposure. After quartz glass exposure, the levels of these parameters are similar to the controls. These results show that the amorphous quartz tested in this experiment (quartz-glass VP 203-006) has to be considered as a compound with certain biological effects. The establishing of occupational standards seems to be justified. But, assessing the effects, the different physical and/or chemical properties of various amorphous quartz dusts have to be considered.
 ...
PMID:[Comparative studies of the effect of quartz glass and quartz DQ-12 in inhalation tests in rats]. 216 66

Heavy maternal alcohol intake is a major perinatal risk but, unfortunately, is difficult for obstetricians and gynecologists to detect. To develop a brief questionnaire appropriate for office detection of "risk-drinking," that is, alcohol intake potentially sufficient to damage the fetus, defined here as greater than or equal to 1 ounce of absolute alcohol per day, we obtained a quantitative drinking history at the first prenatal visit from 971 consecutive gravid women who admitted ever having drunk alcohol. In addition, we administered the 25-question Michigan Alcoholism Screening Test and the four CAGE questions (C = cut down, A = annoyed, G = guilt, E = eye opener), a screening test previously unstudied in pregnancy, and sought evidence of tolerance to the inebriating effect of alcohol, a question which does not appear to trigger psychologic denial. The patient was considered tolerant if it took greater than 2 drinks to make her feel "high." Among 42 (4.3%) risk-drinkers and 929 women who did not report drinking at risk levels, four questions were found to contribute to reliably differentiating risk-drinkers from non-risk-drinkers (R2 = 14.6%, p less than 0.0001). The probability of risk-drinking increased from 1.5% for those responding negatively to 62.7% for those responding positively to all four questions (T = tolerance, A = annoyed, C = cut down, E = eye-opener; odds ratio = 109X). A simple scoring scheme (2 points for T and 1 each for A, C, or E, with a total score of greater than or equal to 2 considered positive) correctly identified 69% of the risk-drinkers (sensitivity) with a positive predictive value of 23%). The T-ACE questions take about 1 minute to ask and represent the first validated sensitive screen for risk-drinking appropriate for routine use in obstetric-gynecologic practice. If validated in further samples, broad application might contribute to better risk identification, secondary prevention efforts, and improved pregnancy outcomes for offspring at risk from heavy prenatal alcohol exposure.
 ...
PMID:The T-ACE questions: practical prenatal detection of risk-drinking. 224 68

We have examined the acute renal failure that occurs after uranyl nitrate administration in the rat and the specific effects of pretreatment of rats with angiotensin converting enzyme inhibitor (CEI), plasma volume expansion (PVE) after uranyl nitrate, and a combination of these treatments. We utilized a combination of micropuncture measurements of glomerular hemodynamics, cage studies, and histologic examination of renal tissue to evaluate the degree of acute renal failure in all groups studied. Uranyl nitrate (UN) (25 mg/kg body wt) administration caused a reduction in the nephron filtration rate (SNGFR) (39.4 +/- 1.6 to 24.8 +/- 2.9 nl X min-1 X g kidney wt-1, P less than 0.02) as a result of a major decrease in the glomerular ultrafiltration coefficient (LpA) from control values (greater than or equal to 0.085 +/- 0.008 to 0.035 +/- 0.007 nl X sec-1 X mm Hg-1 X g kidney wt-1, P less than 0.01). Treatments with CEI, PVE, and the combination of CEI and PVE in rats receiving UN restored 0.38 +/- LpA to normal values (greater than 0.061 +/- 0.009, 0.091 +/- 0.020, and 0.138 +/- 0.020 nl X sec-1 X mm Hg-1 X g kidney wt-1, respectively). Cage studies revealed that CEI treatment prevented oliguria and resulted in major volume losses and reduction in weight. However, rats died after a similar period after UN, but probably by different mechanisms. Analysis of renal ultrastructure revealed equivalent tubular damage in all experimental groups. Alterations in LpA after UN are functional in nature and are potentially preventable and reversible by a combination of treatments with CEI and PVE.
 ...
PMID:Functional basis for the glomerular alterations in uranyl nitrate acute renal failure. 300 41

The efficacy of alcohol screening questionnaires, the TWEAK, T-ACE, NET, MAST, and CAGE, in detecting periconceptional risk-drinking, > or = 1 oz absolute alcohol/day, was investigated in 4743 African-American women attending an inner-city prenatal clinic who had reported ever drinking. Sensitivity, specificity, positive predictive value, efficiency, follow-up rates, and receiver operating characteristics of the questionnaires were examined to compare the overall effectiveness of the questionnaires and their performance at cut-points defining positive scores ranging from 1 to 3. Relatively little difference between TWEAK, T-ACE, and MAST was seen in the receiver operating characteristic accuracy indices; NET and CAGE lagged behind. Sensitivity/specificity scores for the two questionnaires most sensitive at cut-point 1 were TWEAK (87/72) and T-ACE (83/75). At cut-point 2, sensitivity was optimized with respect to specificity; TWEAK (79/83) was significantly more sensitive than T-ACE (70/85; p = 0.002). At cut-point 3, the two most sensitive tests were MAST (61/92) and TWEAK (59/94). In general, measures of merit were not greatly affected by the time between conception and the administration of the screens. Screening was most sensitive for women interviewed during the first 15 weeks of pregnancy; risk-drinkers tended to delay entry into prenatal care, increasing positive predictive values associated with screening later in pregnancy. This study confirms the utility, when screening for risk-drinking during pregnancy, of brief questionnaires that assess alcohol intake indirectly by asking women about their tolerance to alcohol's effects, psychological consequences of drinking, and significant others' concern about their drinking. It validates T-ACE and provides preliminary data indicating that TWEAK may outperform T-ACE.
 ...
PMID:Screening for pregnancy risk-drinking. 784 99

The association between the use of calcium channel blockers (CCB) and cancer has received ample attention, but is still controversial. In this study, we have tested the hypothesis that the observed association between CCB and cancer in earlier studies could be explained by residual confounding or by misclassification of exposure because of the use of cross-sectional data on drug use. Data from the Rotterdam Study, a prospective population-based cohort study in the municipal area Ommoord, were used. The study population consisted of a cohort of 3204 participants aged 71 years or older who were followed from a baseline interview in the period 1991-1993 for the occurrence of incident cancer. Data on drug use were gathered at baseline and through the seven community pharmacies which served the Ommoord region during the study period between 1 January 1991 and 1 January 1999. Incident cancer events were gathered from a nationwide registry of hospitalisation data and from a specialised cancer centre in the Rotterdam region. We performed three analyses. First, we followed the method, and adjusted for the same risk factors, as in the earlier studies. In the second analysis, we included all risk factors that were univariately associated with cancer in the Rotterdam Study. In the third analysis, we included exposure to CCBs as time-varying co-variates, while adjusting for potential confounders. The relative risk (RR) of cancer associated with CCB was 1.4 (95% Confidence Interval (CI): 0.9-2.0) in the first analysis and lowered to 1.2 (95% CI: 0.8-1.8) upon adjustment for the different co-variates in the second. In both analyses, however, verapamil was significantly associated with cancer with RRs of 2.1 (95% CI: 1.1-4.0) and 2.0 (1.01-3.9), respectively, whereas no associations were found with the other CCB in this study, i.e. diltiazem and nifedipine. A significantly increased risk of cancer was found for intermediate daily doses of verapamil and diltiazem. Intake of other antihypertensives such as beta-blocking agents, diuretics and ACE-inhibitors was not associated with cancer. In the third analysis with exposure to CCB as time-varying co-variates, the risk increase was non-significant for use of 2 years or less, 1.0 (95% CI: 0.7-1.5), and for use for a cumulative period of more than 2 years, 1.3 (95% CI: 0.8-2.0). However, in all models the hazard ratio was statistically significantly increased for verapamil, but not for diltiazem and nifedipine. On the basis of these analyses, we found no increase in cancer in users of diltiazem and nifedipine, nor in users of other antihypertensives. In line with earlier studies, however, we found an increased risk of cancer in users of verapamil. At variance with the conclusions from several other studies, we think that it is too early to conclude that CCB are not associated with cancer.
 ...
PMID:Verapamil is associated with an increased risk of cancer in the elderly: the Rotterdam study. 1250 52

The goal of this study was to determine the dependence of the acute hypertensive response to a novel model of acute psychosocial stress on the sympathetic and renin-angiotensin systems. Baseline mean arterial pressure (MAP), heart rate (HR), and locomotor activity were measured with telemetry in mice for a 1-h period and averaged 98 +/- 1 mmHg, 505 +/- 3 beats/min, and 5 +/- 1 counts, respectively. Stress was induced by placing a mouse into a cage previously occupied by a different male mouse, and this increased MAP, HR, and activity in the control group by 40 +/- 2 mmHg, 204 +/- 25 beats/min, and 68 +/- 6 counts, respectively. Each variable gradually returned to baseline levels by 90 min after beginning cage switch. Pretreatment with terazosin (10 mg/kg ip) significantly reduced the initial increase in MAP to 12 +/- 6 mmHg, whereas MAP for the last 45 min was superimposable on control values. Atenolol (10 mg/ml drinking water) had no effect to blunt the initial increase in MAP but had a growing effect from 10 min onward, decreasing MAP all the way to baseline by 60 min after starting cage switch. Captopril (2 mg/ml drinking water) treatment caused a very similar response. All three treatments significantly decreased the area under the blood pressure curve, and the blood pressure effect could not be attributed uniformly to effects on HR or activity. These data suggest that our novel model of psychosocial stress causes an initial alpha(1)-receptor-dependent increase in MAP. The later phase of the pressor response is blocked similarly by a beta(1)-receptor antagonist and an ACE inhibitor, independent of HR, suggesting that the beta(1)-dependent blood pressure effect is due, in large part, to the renin-angiotensin system.
 ...
PMID:Sympathetic and angiotensin-dependent hypertension during cage-switch stress in mice. 1530 86

A biased Monte Carlo-minimization/annealing conformational search was used to characterize five descriptions of the energy landscape for each of three model systems: the 20-residue "trp-cage" miniprotein, the 20-residue "BS1" peptide, and the 17-residue "U(1-17)T9D" peptide. The EEF1 and SASA energy landscapes were studied as well as those defined by using the GB/ACE implicit water model with one of three protein force fields: CHARMM19, CHARMM22, and CHARMM22/CMAP. The lowest-energy structures of the trp-cage and BS1 peptides found for the EEF1 landscape have main-chain root-mean-square deviations (rmsds) from the respective NMR structures of less than 2 A; for U(1-17)T9D, the deviation is less than 3 A using EEF1. The main-chain rmsd of the minimum-energy trp-cage conformation obtained for the GB/ACE/CHARMM22/CMAP landscape is less than 1 A. However, this energy function strongly favored helical structures for the two peptides shown by NMR to form beta-sheet structures. Brief annealing of the system following main-chain conformational changes was found to enhance the exploration of low-energy states. The thousands of simulations reported here suggest that the prediction of protein structure might be improved by the simultaneous use of a CMAP-like description of the main chain and an EEF1-like description of the solvent.
 ...
PMID:Exploring peptide energy landscapes: a test of force fields and implicit solvent models. 1539 Feb 66

CGS 35601 is a triple vasopeptidase inhibitor (VPI) of angiotensin converting enzyme (ACE), neutral endopeptidase (NEP), and endothelin (ET) converting enzyme-1 (ECE-1), with respective IC(50) values of 22, 2, and 55 nM. The aim of the present study was to establish the hemodynamic profile of Zucker diabetic fatty (Zdf)-Fatty rats, a high-fat diet gene-prone model developing spontaneous Type 2 diabetes (T2D) and the effects of CGS 35601. Male Zdf-Fatty (14 weeks, n = 17-23), Zdf-Lean (14 weeks, n = 8-10), and Wistar (14 weeks, n = 9-10) rats on distinct diets were implanted with a catheter in the left carotid and placed individually in a metabolic cage for 30 days. The hemodynamic profile and some metabolic biomarkers were assessed daily. After a 7-day stabilization period, the Zdf-Fatty rats were divided into two groups: Group 1, controls (n = 7-10) receiving vehicle-saline (250 microl/hr) and Group 2, (n = 10-13) receiving increasing doses of CGS 35601 (0.1, 1, and 5 mg/kg/day x 6 days each, intra-arterially) followed by a 5-day washout period. Mean arterial blood pressure (MABP) of young Zdf-Fatty rats was compared with age-matched Zdf-Lean and Wistar rats, which were found similar. MABP decreased by 5.9% (from baseline at 102 +/- 5 to 96 +/- 4 mmHg), 12.7% (to 89 +/- 6 mmHg) and 21.6% (to 80 +/- 4 mmHg), at 0.1, 1, and 5 mg/kg/day, respectively, in CGS 35601-treated Zdf-Fatty rats. Systolic and diastolic blood pressures were similarly reduced. The heart rate was not affected. Hyperglycemic status and insulin-resistance were not modulated by short-term treatment. CGS 35601 presented an excellent short-term safety profile. This novel molecule and class of VPI may be of interest for lowering vascular tone. Further long-term studies, once cardiovascular and renal complications have developed in this T2D rat model are warranted to define the efficacy of this class of VPI.
 ...
PMID:The hemodynamic and metabolic profiles of Zucker diabetic fatty rats treated with a single molecule triple vasopeptidase inhibitor, CGS 35601. 1674 Oct 6

Fetal alcohol exposure affects approximately 1% to 3% of live births in the United States. Family physicians are in a unique position to reduce the incidence of alcohol-exposed pregnancy. Fetal alcohol exposure can be minimized through 2 general approaches: reducing alcohol consumption or increasing effective contraception among childbearing-aged women who engage in "at-risk" drinking and encouraging pregnant women to abstain from alcohol. Although no safe level of alcohol consumption during pregnancy is established, women who binge drink are more likely to deliver infants with physical and cognitive-developmental anomalies. Screening tools, such as quantity/frequency questions, the TWEAK and the T-ACE, developed specifically for prenatal care, are more useful with women than the CAGE and Michigan Alcohol Screening Test (MAST). Screening alone seems to reduce alcohol use among pregnant women. Brief interventions, including education about alcohol's effects on the developing fetus, are effective among women not responding to screening. Unfortunately, many barriers exist to effective implementation of alcohol-exposed pregnancy (AEP) prevention in the clinical setting. Designing effective office base systems so the entire burden of implementing AEP prevention activities does fall solely on the family physician is critical.
 ...
PMID:Preventing alcohol-exposed pregnancies. 1695 Dec 99


1 2 Next >>