摘要:

AbstractCold air inhalation challenge (CAIC) for the evaluation of bronchial reactivity has been proposed as a physical agent alternative to chemical agent challenges (methacholine or histamine), especially suitable for the occupational environment. The present investigation describes and evaluates a method for performing cold air inhalation challenge in Cynomologus monkeys (Macaca fascicularis), a species shown to be useful in animal modeling studies of occupational asthma. Six adult male anesthetized monkeys were ventilated by changes in external pressure while breathing cold air (−25°C to −30°C). Pulmonary function testing was performed at 10, 25, 40 and 55 min post‐challenge. Significant increases (P<0.05) in average pulmonary flow resistance (RL) and decreases in dynamic compliance (CL dyn) were observed, with maximum impairment occurring at 25 min post‐challenge, with a trend towards a return to baseline values at 55 min post‐challenge. Peak expiratory flow rate (PEFR), forced expiratory volume in 0.5 s/forced vital capacity (FEV0.5/FVC) and forced expiratory flow at 50% forced vital capacity (FEF50) showed the same general pattern of reduction as seen withRL; however, these results were not statistically significant, most probably owing to individual monkey variability and the small number of monkeys (N= 6) used. A repeat challenge at 25 min after a primary challenge yielded increasedRLin one monkey, suggesting that no absolute refractory period is present from CAIC. Results of these studies demonstrate that CAIC causes bronchoconstriction in monkeys and may be useful in further animal modeling studies designed to determine the asthmogenic/airway irritant potential of occupationa

ISSN:0260-437X    

DOI:10.1002/jat.2550110102

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractDimercaptosuccinic acid (DMS), HOOC‐CH(SH)‐CH(SH)‐COOH, was first developed in China as an effective antidote for poisoning from many heavy metals, such as Pb, Hg, As, Cd, Sb, TI, Au, Zn, Ni, Pt, Ag, Co and Sn. DMS increases the excretion of Ce, Pm, Sr and Po from the body. Hundreds of patients suffering from hepatolenticular degeneration (Wilson's disease) have been treated successfully with DMS. Recently, DMS was found to be effective also in treating certain non‐metallic intoxications, like some of the new non‐phosphate pesticides and mushroom p

ISSN:0260-437X    

DOI:10.1002/jat.2550110103

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractSpecies differences in metabolism, tissue localization, specificity and sensitivity for cardiac damage influence the choice of biochemical investigation used in the assessment of cardiotoxicity. The tests currently used in toxicological studies are broadly categorized herein as enzymes and other proteins, lipids and electrolytes; some limitations of these tests are also discussed.

ISSN:0260-437X    

DOI:10.1002/jat.2550110104

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractPregnant Sprague‐Dawley rats were injected intraperitoneally with physiological saline solution (vehicle) or cadmium chloride (CdCI2) at 2.0 or 2.5 mg kg−1on days 8, 10, 12 and 14 of gestation. On postnatal day (PND) 3, 12 or 49, the offspring were examined for 8‐ or 24‐h urinary excretion of β2‐microglobulin (β2‐m), metallothionein (MT) and urinary activity of three proximal tubular enzymes: gammaglutamyl transferase (GGT), alkaline phosphatase (ALP) andN‐acetyl‐β‐glucosaminidase (NAG).Treatment with CdCI2did not affect growth or survival of offspring. Significant decreases in the urinary excretion of GGT, ALP and NAG were observed on PND 3, at both doses. Exposure to 4 × 2.5 mg kg−1resulted in functional deficit of the proximal tubule on PND 3, as evidenced by the significant increase in β2‐m. Except for a slight but significant increase of β2‐m in 49‐day‐old males, all the other urinary parameters returned to control values on PND 12. There was no effect on MT.Results from this study show that prenatal exposure to CdCI2can induce significant changes in the kidney biochemistry of r

ISSN:0260-437X    

DOI:10.1002/jat.2550110105

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe effect of calcium channel blocking agents on the reductive metabolism of halothane in liver microsomes of guinea pigs was investigated. The reaction mixture for the measurement of the end products consisted of microsomal suspension, 5 mM NADPH, calcium channel blocking agents (verapamil, diltiazem, nicardipine and nifedipine) and halothane in 0.1 M phosphate buffer (pH 7.4). The reductive metabolism of halothane was inhibited competitively by verapamil, diltiazem and nicardipine. The binding spectra for the interaction of these three drugs with cytochrome P‐450 in microsomes were investigated. Verapamil caused the reverse type I difference spectrum and diltiazem caused the type I difference spectrum. However, the change caused by nicardipine was not observed by the presence of its specific spectra. NADPH–cytochrome P‐450 reductase activity in microsomes did not change by the addition of these three drugs. These results suggest that these three calcium channel blocking agents inhibit the production of radical intermediates during the reductive metabolism of halo

ISSN:0260-437X    

DOI:10.1002/jat.2550110106

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractCentral to both the scientific development of behavioral teratology and the attention paid to this field as an important area of study is establishing that prenatal exposure of pregnant females to exogenous agents leads to neurobehavioral disorders in their offspring. This tenet may not be questioned by the majority of toxicologists, but others may not be convinced. This paper serves as a brief review of the accumulated evidence that prenatal exposure to a number of drugs and environmental/industrial agents produces behavioral disorders in human infants.

ISSN:0260-437X    

DOI:10.1002/jat.2550110107

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe embryolethality of butyl benzyl phthalate (BBP) was studied in Wistar rats. Pregnant rats were given BBP at dosages of 0 (control) and 2.0% in the diet from day 0 to day 20 of pregnancy. Daily intake of BBP was 974 mg kg−1for the 2.0% BBP group. In this group, all dams exhibited complete resorption of all the implanted embryos, and their food consumption, body weight gain and adjusted weight gain (body weight gain excluding the gravid uterus) during pregnancy were markedly lowered. To determine whether the embryolethality was the result of reduced food consumption during pregnancy, a pair‐feeding study was performed in which the pregnant rats received the same amount of diet consumed by the 2.0% BBP‐treated pregnant rats. The pair‐fed and 2.0% BBP‐treated pregnant rats showed significant and comparable reductions in the adjusted weight gain. In the pair‐fed group, the incidences of postimplantation and total losses were higher than those in the control group, and the number of live fetuses per litter was lower than the control value. However, the complete resorption of all the implanted embryos was not found in any of the pair‐fed pregnant rats. It could be concluded that the embryolethality observed in the 2.0% BBP‐treated pregnant rats is attributable to the effects of dietary BBP but not to the maternal malnutrition from reduced food consumption d

ISSN:0260-437X    

DOI:10.1002/jat.2550110108

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractVentricular hypertrophy induced in male Sprague‐Dawley rats by inhalation of 500 ppm carbon monoxide (40% carboxyhemoglobin level) for 0–62 days was assessed by contiguous 2‐mm thick axial cardiac crosssections, using 32 accumulated averages of ungated fast‐scan gradient‐recalled nuclear magnetic resonance (NMR) images. Following final imaging, the rats were sacrificed and the hematocrit and heart mass were determined. The mean outside diameter of the left ventricle plus interventricular septum (LV + S) showed a strong correlation (r= 0.73,P<0.01) with the duration of CO exposure, while the correlation coefficients for the LV + S Iumen diameter and wall thickness were marginally significant. The mean pleural space diameter also increased significantly (r= 0.64,P<0.05) with the duration of CO exposure. The ratio of LV + S wall thickness and the Iumen radius was 0.53 in the rats exposed to CO for 0–8 days; this value did not change with longer CO exposure. The LV + S outside and Iumen diameter showed significant correlations to the hematocrit (r= 0.72,p<0.05 andr= 0.66,P<0.05, respectively), and the LV + S outside diameter correlated with the increase in the LV + S mass (r= 0.72,P<0.05). The results achieved with NMR imaging are consistent with past morphometric studies of CO‐induced ventricular hypertrophy, where heart dimensions were determined in relaxed frozen tissue, and corroborate the eccentric nature of CO‐induced ventricu

ISSN:0260-437X    

DOI:10.1002/jat.2550110109

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractPolychlorotrifluoroethylene (polyCTFE—primarily oligomers with 3–4 monomer units), a non‐flammable hydraulic fluid for aircraft, was given daily for 15 days by oral gavage to four Rhesus monkeys at a concentration of 0.725 g kg−1. The administered dose was at a level that had caused toxicity in rats. Steady‐state blood and liver concentrations reached were the same in both species. In monkeys, polyCTFE did not cause the electrolyte, serum protein, liver enzyme and anemic disturbances previously seen in rats. Liver sections taken at 15 days, analyzed for palmitoyl Co‐A beta‐oxidation rates or by electron microscopy, showed no significant indication of peroxisomal proliferation. An increased blood urea nitrogen (BUN) at 15 days was the only clinical pathological abnormality seen in both monkeys and rats. Previously unobserved effects were increased triglycerides and glyco

ISSN:0260-437X    

DOI:10.1002/jat.2550110110

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe level of neurotoxic esterase in brain, spinal cord and platelets of certain birds and mammals has been determined. The enzyme activity for the birds was maximal in hens and for the mammals was maximal in rats. The activity decreased progressively in the cerebral cortex, corpus striatum, spinal cord and blood platelets of the birds as well as the mammals. The difference in the susceptibility of birds and mammals to organophosphate‐induced delayed neurotoxicity may be related to differences in the relative concentrations of the enzyme in the different specie

ISSN:0260-437X    

DOI:10.1002/jat.2550110111

出版商:John Wiley&Sons, Ltd.    

年代:1991

数据来源: WILEY