摘要:

AbstractThe pharmacokinetic behaviour and the mechanism of renal excretion of stanozolol (STZ), as affected by cotreatment with probenecid, were studied in male Sprague‐Dawley rats. Pharmacokinetic parameters following intravenous (i.v.) administration of STZ (20 mg kg−1body wt.) were measured in both STZ‐treated (control) and STZ plus probenecid‐treated (treatment) groups. In order to assess the renal clearance of STZ, bolus doses of STZ and inulin (40 mg kg−1body wt.) were injected i.v. either in the presence or absence of probenecid (40 mg kg−1body wt.). The blood and urine concentrations of STZ were determined by capillary gas chromatography‐mass spectrometry (GC‐MS).In the probenecid treatment group, the area under the plasma disappearance and urinary excretion curves (AUC) of STZ were significantly decreased (P<0.01) and the volume of distribution (Vd) and total clearance (CLt) were significantly increased statistically (P<0.05 andP<0.01, respectively). No remarkable differences in the urine flow rate, urine pH values, glomerular filtration rate (GFR) or renal clearance were observed in the treatment group. However, the clearance ratio in the treatment group was significantly increased from 11.72 to 17.27. From these results, it is suggested that the significant decrease of AUC, i.e. increase of disappearance of STZ in plasma by co‐administration with probenecid, is due to the increase of th

ISSN:0260-437X    

DOI:10.1002/jat.2550120605

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractPerfluoroisobutene (PFIB) is produced by the pyrolysis, and as a by‐product during the manufacture, of polytetrafluoroethylene. When inhaled it produces a fulminating and sometimes fatal pulmonary oedema similar to that of phosgene after a latent period of 6–8 h. As part of a study to determine the retained dose and the factors that control the amount retained, this study has investigated the retention in rats of inhaled PFIB at concentrations of 10, 50 and 250 μg l−1in a flow‐through system combining head‐only exposure and plethysmography. Uptake of PFIB was measured by gas chromatography during elevated and reduced inspired volume and respiratory rate induced by exposure to increased CO2and injection of pentobarbitone, respectively. The percentage of PFIB retained in the upper airways and lungs was found to be 27.5, 28.1 and 23.7% of the amount inspired at the three concentrations tested. The rate of uptake (nmol min−1kg−1) of PFIB was a power law of the amount inhaled, annb‐fold increase in minute volume producing ann‐fold increase in uptake, wherebvaried between 0.4 and 0.85. Thus, doubling the inhaled dose produces a 1.3–1.8‐fold increase in uptake with a corresponding decrease in percentage retained. The relative contribution of respiratory rate and tidal volume upon PFIB retentio

ISSN:0260-437X    

DOI:10.1002/jat.2550120606

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

ISSN:0260-437X    

DOI:10.1002/jat.2550120607

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractMagnetic resonance (MR) may be used for repeatedly and non‐invasively imaging the brain. Until now, no studies have used this approach to study the effects of carbon monoxide (CO) poisoning in a defined animal model. Conscious, Levine‐prepared female rats (unilateral carotid artery and jugular vein occlusion) were exposed to 2400 ppm CO for 90 min, with or without the infusion of 50% glucose solution; CO‐stimulated increases in blood glucose and lactate occurred in both groups, while blood pressure and body temperature fell. One to four hours following termination of CO exposure, increased cortical pixel intensity, cortical surface area and brain midline shift were observed on the operated side of the brain in some rats of both groups (i.e. responders = R), providing evidence of edema. At sacrifice, 5 h following termination of CO exposure, gross water content was increased on the left side in the corresponding cortical slices in R rats, providing another measure of edema. Significant positive correlations were found between left to right pixel intensity difference and water content difference, and between the extent of midline shift and water content difference. The elevations of blood glucose and lactate concentrations, and the magnitudes of CO‐induced hypothermia and hypotension were similar to those in past studies, but appeared to exert no effect on the severity of cortical edema in terms of differences in pixel intensity, surface area, midline shift or gross tissue water content. Thus, the observed differences between the R rats and the non‐R rats is not explained by the available data. The results of this study demonstrate that MR imaging can detect changes in the cerebral cortices of rats given an acute toxic challenge with CO. Moreover, in responders the edema develops quickly, reaching nearly full development within 1 h after CO

ISSN:0260-437X    

DOI:10.1002/jat.2550120608

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThis report presents a set of investigations on the hepatotoxic action of acetaminophen (AA). Male mice of Balb C strain were given [3H]acetaminophen in doses of 100, 300 and 600 mg kg−1with or without pretreatment with 3‐methylcholanthrene (3MCh) or diethyl maleate (DEM).The results of this study show that AA administered in moderate doses brings about necrotic changes due to adduct formation with macromolecules. Adduct formation was inversely correlated with the level of glutathione.Both modifiers enhanced hepatic necrosis and lethality. Diethyl maleate exerted these effects without enhancing covalent binding to macromolecules, while 3MCh increased both adduct formation and lipid peroxidat

ISSN:0260-437X    

DOI:10.1002/jat.2550120609

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractRecent evidence has shown that exposure to pesticides can lead to long‐term neurophysiological and functional deficits. We have demonstrated previously that locomotion in chicks exposed to some organophosphates and carbamates could be altered persistently without concomitant central or peripheral esterase inhibition. Furthermore, histopathology of the ataxic chickens showed no lesions in either the central or peripheral systems. In this study, we examined whether locomotion alterations seen in chicks exposedin ovoto carbaryl and aldicarb are accompanied by perturbations in particular central neurotransmitter systems. Carbaryl and aldicarb were injectedin ovoon day 15 of incubation at 6, 16 and 65 mg kg−1egg weight and at 0.2, 0.4 and 3.5 mg kg−1egg weight, respectively. Neurotransmitter levels (assayed by high performance liquid chromatography with electrochemical detection) and locomotion were measured at various times (1–43 days) after dosing. At the lower doses of both carbaryl and aldicarb, a trend towards prolonged decreases in cerebral dopamine and homovanillic acid was seen. The high dose of carbaryl significantly reduced dopamine and the high dose of both compounds significantly decreased homovanillic acid and 5‐hydroxyindoleacetic acid. Persistent locomotion alterations were observed only at the higher doses of both carbaryl and aldicarb when the specific neurotransmitters measured returned to norm

ISSN:0260-437X    

DOI:10.1002/jat.2550120610

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractAn experimental study was conducted to evaluate changes in pulmonary reactivity resulting from repeated vanadium pentoxide (V2O5) dust inhalation. The study assessed pulmonary reactivity to V2O5through the use of provocation challenges, and compared V2O5reactivity before and after subchronic V2O5exposure. A total of 24 adult, male cynomolgus monkeys (Macaca fascicularis) were exposed by inhalation for 6 h per day, 5 days per week, for 26 weeks. Two V2O5‐exposed groups (n=8 each) received equal weekly V2O5exposures (concentration x time) with different exposure profiles. One V2O5‐exposed group received 0.1 mg V2O5m−3on Mondays, Wednesdays and Fridays, with a twice‐weekly peak exposure of 1.1 mg V2O5m−3on Tuesdays and Thursdays, and was included to investigate the influence of an exposure regimen with peaks on the development of pulmonary hyper‐reactivity. The other V2O5‐exposed group received a constant daily concentration of 0.5 mg V2O5m−3. A control group (n‐8) received filtered, conditioned air. Pre‐exposure challenges with V2O5produced a concentration‐dependent impairment in pulmonary function, characterized by airway obstructive changes (increased resistance and decreased flow). Analysis of respiratory cells recovered from the lung by bronchoalveolar lavage demonstrated that airway obstruction was accompanied by a significant influx of inflammatory cells into the lung. Subchronic V2O5inhalation did not produce an increase in V2O5reactivity in comparison to the control group, and cytological, immunological and skin test results indicate the absence of allergic sensitization. Instead, a trend toward decreased pulmonary reactivity was found following subchronic V2O5inhalation. Pulmonary reactivity to V2O5(both functional and cellular responses) was affected, as well as non‐specific reactivity to methacholine. This finding suggests that the absence of increased pulmonary reactivity to V2O5following subchronic inhalation may be related to the induction of tolerance under the exposure condi

ISSN:0260-437X    

DOI:10.1002/jat.2550120611

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractA 10‐year (1980 to 1989 inclusively) retrospective analysis of poisoning admissions to the six major referral hospitals in Zimbabwe revealed 6018 cases. The majority of the patients were aged 0–5 years (35%) and 21–30 years (22.6%). The main agents associated with acute poisoning were traditional medicines (22.9% of the total), household chemicals (18.8%, 13.2% of which was due to paraffin), snake and insect envenomation (17.1%), orthodox medicines (16.7%) and insecticides (14.8%, 10% of which is accounted for by organophosphates). Mortality was 15% and the main agents associated with fatality were pesticides, traditional medicines and orthodox medicines, in descending order. The prevention and treatment of intoxication caused by traditional and orthodox medicines, the proper storage and disposal of pesticides and legislation regulating their sale and distribution are of high priority in the fight to reduce poisoning caused by these a

ISSN:0260-437X    

DOI:10.1002/jat.2550120612

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe effect of silymarin on liver damage induced by acetaminophen (APAP) intoxication was studied. Wistar male rats pretreated (72 h) with 3‐methylcholantrene (3‐MC) (20 mg kg−1body wt. i.p.) were divided into three groups: animals in group 1 were treated with acetaminophen (APAP) (500 mg kg−1body wt. p.o.), group 2 consisted of animals that received APAP plus silymarin (200 mg kg−1body wt. p.o.) 24 h before APAP, and rats in group 3 (control) received the equivalent amount of the vehicles. Animals were sacrificed at different times after APAP administration. Reduced glutathione (GSH), lipid peroxidation and glycogen were measured in liver and alkaline phosphatase (AP), gamma‐glutamyl transpeptidase (GGTP) and glutamic pyruvic transaminase (GPT) activities were measured in serum. After APAP intoxication, GSH and glycogen decreased very fast (1 h) and remained low for 6 h. Lipid peroxidation increased three times over the control 4 and 6 h after APAP treatment. Enzyme activities increased 18 h after intoxication. In the group receiving APAP plus silymarin, levels of lipid peroxidation and serum enzyme activities remained within the control values at any time studied. The fall in GSH was not prevented by silymarin, but glycogen was restored at 18 h. It was concluded that silymarin can protect against APAP intoxication through its antioxidant properties, possibly acting as a free‐radi

ISSN:0260-437X    

DOI:10.1002/jat.2550120613

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractDusting powders are used on latex gloves and condoms. They help to release these products from their moulds during manufacture and facilitate processing and donning. Dusting powders are also used on contraceptive diaphragms, sanitary napkins and in toiletries. There are numerous dusting powders in current use around the world. At present a consensus exists about the best dusting powder to use on surgical gloves, based on data about the safety of these agents in humans, as well as their manufacturing qualities. No such consensus exists for the use of dusting powders in other situations. However, there is uncertainty about whether dusting powders used in situations other than on surgical gloves are responsible for harmful effects. This study uses intraperitoneal injections in rats to examine the pathological effects of dusting powders that are in current use on surgical gloves and condoms. We suggest that dusting powders may be a source of morbidity when used in situations other than on surgical gloves and confirm the findings of previous investigators that the dusting powders we tested differ in their ability to produce pathological effects.

ISSN:0260-437X    

DOI:10.1002/jat.2550120614

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY