摘要:

To test the hypothesis that the high absorption of manganese (Mn) in suckling rats compared to weanling rats is due in part to maturational differences in mucosal cell uptake of Mn, uptake kinetics of Mn were examined in isolated brush‐border membrane vesicles prepared from the small intestine of rats at various ages (d 14, d 18, d 21). Initial uptake of Mn was rapid by vesicles from all age groups and reached an equilibrium plateau by 5 min in vesicles from suckling rats (d 14) and 10 min in vesicles from weanling rats (d 18, d 21). Uptake of Mn was associated with an osmoti‐cally active space.

ISSN:0098-4108    

DOI:10.1080/15287398909531263

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

The advantages of using homogeneous experimental groups (inbred animal strains) and of using multiple groups within an experiment, based on the power of the Mantel‐Haenszel test, were investigated. A simulation experiment was performed to empirically calculate the power of a one‐sided Mantel‐Haenszel test for multistrain experiments. In each case, the power of the multistrain experiment was compared to the (empirical) expected value, over strains, of the power where each strain is tested individually. In the simulation, use of subgroups, each having different response rates, resulted in an increase in power where a chemical exposure caused an average increase of effects in 10% or more of the animals across strains.

ISSN:0098-4108    

DOI:10.1080/15287398909531264

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

Cutaneous absorption and decontamination of [3H]T‐2 mycotoxin using various treatment modalities incorporating water, detergent, sprays, and scrubbing of application sites were examined in the rat model at 5, 30, 60, and 1440 min (24 h) postexposure. Rats were killed immediately after treatment and radiolabeled T‐2 remaining in full‐thickness skin samples was determined. Absorption and decontamination were followed over time, and decontaminating treatment modalities were evaluated for efficacy. Less than 1% of the applied dose was absorbed in 5 min, and 50% was absorbed in 24 h. At 5 min, 99.5 ± 0.05% of nonabsorbed (residual) [3H]T‐2 was removed, and 58 ± 5.2% of residual toxin was removed at 24 h with a 2.5% detergent/water spray. When treatment modalities were evaluated at 60 min, a 2.5% detergent/water scrub followed by a detergent/water spray produced optimal decontamination by removing 81 ± 2.2% of residual toxin. All treatment modalities using detergent and/or water removed significant amounts of toxin (p≤ .0001); a dry scrub was not efficacious. Treatment should be initiated as soon as possible after exposure for best results. However, the stratum corneum acts as a reservoir for the toxin, and decontamination should be carried out even if delayed several hours or days after exposure. Dermal absorption pharmacokinetics found in these studies are similar to those described for other low‐molecular‐weight compounds, and the decontamination results from T‐2 toxin should be applicable to other, similar toxic substances.

ISSN:0098-4108    

DOI:10.1080/15287398909531265

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

Beta agonists such as isoproterenol are widely used in the treatment of acute asthmatic attacks. It would not be unexpected that some patients receiving isoproterenol might have ingested caffeine as an over‐the‐counter drug or beverage. This study explores the possible interaction between these two drugs. Anesthetized mini pigs were injected with 0.5 mg/kg caffeine iv followed by a 10‐min infusion of 1 μg/kg·min isoproterenol. Heart rate, EKG, respiration, and blood pressure were recorded continuously and the animals were sacrificed at 72 h. The two drugs in combination produced subtle changes in heart rate and blood pressure with significant alteration in the EKG tracing (premature ventricular contractions and extrasystoles). These changes persisted for 8 to 24 h. At autopsy both gross and microscopic lesions were noted in 10 of the 13 minipig hearts receiving the combination of drugs. This was not true of the six minipigs given only caffeine or the eight minipigs receiving only the infusion of isoproterenol. No changes in EKG tracings or pathologies were noted with caffeine and only two of eight animals infused with isoproterenol showed any lesions.

ISSN:0098-4108    

DOI:10.1080/15287398909531266

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

The LD50s and ED50s for inhibition of acetylcholinesterase (AChE) in whole mouse brain by DFP (diisopropylfluorophosphate), sarin (methylphosphonofluoridic acid 1‐methyl ethyl ester), soman (methylphosphonofluoridic acid 1,2,2‐trimethyl propyl ester), and tabun (dimethylphosphoramidocyanidic acid ethyl ester) were compared after iv administration. The LD50s of DFP, sarin, soman, and tabun in ICR (Institute for Cancer Research) mice were 3.40, 0.109, 0.042, and 0.287 mg/kg, respectively. The recovery of AChE activity in whole mouse brain after sub‐LD50 doses of these agents was slow and did not reach control values by 14 d after iv administration. AChE activity was inhibited in a dose‐dependent manner in whole mouse brain, as well as in six brain regions (cortex, hippocampus, striatum, midbrain, medulla‐pons, and cerebellum). None of these brain areas appeared to be particularly sensitive to AChE inhibition. The ED50s for DFP, sarin, soman, and tabun for inhibition of AChE in whole mouse brain were approximately 19, 38, 69, and 66% of their respective LD50s. Because of the differential potencies between lethality and inhibition of AChE, it is concluded that the lethality of these agents is due to more factors than simply the inhibition of AChE within the brain.

ISSN:0098-4108    

DOI:10.1080/15287398909531267

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

Pretreatment of rats with the nonspecific esterase inhibitor iso‐OMPA (1 mg/kg sc) 1 h prior to carbofuran (2,3‐dihydro‐2,2‐dimethyl‐7‐benzofuranylN‐methylcarbamate, 0.5 mg/kg sc) administration potentiated carbofuran toxicity by more than threefold. Neither iso‐OMPA nor carbofuran in the given doses produced any gross toxic signs. Rats receiving combined treatment, however, showed severe hypercholinergic signs (salivation, tremors, muscle fasciculations, and convulsions) within 5–10 min following carbofuran administration, and the severity was comparatively greater than that observed with an acute dose of carbofuran (1.5 mg/kg sc). Rats pretreated with iso‐OMPA (0.5 mg/kg) died within 10–15 min following the acute dose of carbofuran (1.5 mg/kg). Each drug when given alone (1.0 mg/kg iso‐OMPA, 0.5 mg/kg carbofuran) caused a significant (p< .01) inhibition of carboxylesterase (CarbE) activity in brain structures (cortex, stem, striatum, and hippocampus), skeletal muscle (hemi‐diaphragm), liver, and plasma, whereas acetylcholinesterase (AChE) activity remained significantly (p> .01) unchanged. The maximal CarbE inactivation in plasma (< 14% remaining activity) following either drug indicated a tremendous nonspecific binding to non‐AChE serine‐containing enzymes. iso‐OMPA pretreatment markedly potentiated carbofuran's anticholinesterase activity both in neuronal and in nonneuronal tissues. It can be concluded that iso‐OMPA pretreatment potentiates carbofuran toxicity either by preventing nonspecific binding of carbofuran to CarbE and/or possibly by inhibiting its detoxification.

ISSN:0098-4108    

DOI:10.1080/15287398909531268

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

Our study presents the in vitro molybdenum influence on benzo[a]pyrene (BaP) micro‐somal metabolism. Addition of various concentrations of different molybdenum salts [MoS2, MoCl5, (NH4)6Mo7O244H2O] to liver and lung microsomal fractions of rats previously treated with 3‐methylcholanthrene produces a decrease in the different BaP metabolites assessed by high‐performance liquid chromatography (HPLC) analysis. This inhibition varies, depending on the considered metabolite and in relation to both the molybdenum level and the origin of the microsomal suspension. The minimum effective concentration is 0.26 and 0.52 mM Mo from liver and lung, respectively. The inhibitory potencies of the +5 (chloride) and +6 (ammonium heptamolybdate) molybdenum compounds are comparable; that of the sulfide is lower.

ISSN:0098-4108    

DOI:10.1080/15287398909531269

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

Human blood mononuclear cells were exposed to ozone in vitro and thereafter analyzed for competence in mitogen‐induced proliferation as well as IL‐1 and IL‐2 production. Proliferative responses induced by phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) were all depressed in lymphocytes exposed to an ozone concentration of 1 ppm for 4–6 h. The response to PWM was most sensitive to the ozone effect (38% suppression); responses to Con A and PHA were suppressed to a lesser extent, 23% and 18%, respectively, and were not significantly different from each other. PWM responses were affected at an ozone concentration as low as 0.1 ppm; however, no suppression of Con A‐induced proliferation was seen below 0.18 ppm or of PHA‐induced proliferation below 0.5 ppm. When lymphocytes and monocytes were exposed separately to ozone and then mixed back with control air‐exposed monocytes or lymphocytes, both cell types appeared to be affected and the functional defects caused by the pollutant were additive. Monocyte IL‐1 production induced by endotoxin was not affected by ozone exposure, while surface expression of HLA‐DR on exposed monocytes was reduced by 40% 24 h after exposure. Moreover, lymphocytes exposed to ozone produced 46% less IL‐2 while expressing similar surface density of IL‐2 receptors. Taken together, these results show that exposure to ozone has distinct adverse effects on lymphocytes and monocytes, both of which are important in local immune defenses in the lung.

ISSN:0098-4108    

DOI:10.1080/15287398909531270

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

Twenty‐two hours after ip administration to male Wistar rats and BALB/c mice, 1,1,1,2‐tetrachloroethane (1,1,1,2‐TTCE) is bound covalently to DNA, RNA, and proteins of liver, lung, kidney, and stomach. The in vivo reactivity leads to binding values to DNA generally higher in mouse organs than in rat organs. The covalent binding index (CBI) values (82 in mouse liver DNA and 40 in rat liver DNA) classify 1,1,1,2‐TTCE as a weak to moderate initiator. Both microsomal and cytosolic enzymatic systems from rat and mouse organs are capable of bioactivating 1,1,1,2‐TTCE in vitro. Liver fractions are the most effective. When the activating systems are simultaneously present in the incubation mixture a synergistic effect is observed. Unlike the related chemical 1,1,2,2‐tetrachloroethane (1,1,2,2‐TTCE), which is bioactivated only through an oxidative route, 1,1,1,2‐TTCE metabolism is carried on by oxidative and reductive pathways, both dependent on cytochrome P‐450. 1,1,1,2‐TTCE is also bioactivated by microsomal CSH‐transferases from liver and lung. These data further confirm that correlations exist between structure and genotoxic activity of halocompounds.

ISSN:0098-4108    

DOI:10.1080/15287398909531271

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor

摘要:

While the pulmonary toxicity of NO2is clearly established, the mechanism by which it is removed from inspired air is poorly understood. Uptake is most likely dependent on chemical reaction since, despite limited per se gaseous NO2aqueous solubility, uptake proceeds rapidly without ready saturation. We utilized an isolated perfused rat lung model to characterize the effect of dose rate on uptake and transformation. Dose rate was varied via alterations in inspired concentration, tidal volume, and ventilation frequency. Dose equaled the total amount inhaled, uptake the amount removed from inspired air, and transformation the amount of NO−2that accumulated in the perfusate. We found a linear proportionality between both inspired concentration (4–20 ppm) and minute ventilation (45–130 ml/min) and uptake. Fractional uptakes (65%) were similar for all groups. Regression of combined concentration and minute ventilation data yielded a linear relationship between total inspired dose (25–330 μg NO2) and both uptake (r2= 0.99) and transformation (r2= 0.98). Testing of the functional descriptions resulted in measured uptakes and transformation that fell within a few percentage points of those predicted. We conclude that in acutely exposed isolated lungs (1) NO2uptake is dependent on total inhaled dose rather than on the variables which serve to affect dose rate, (2) transformation is related to both total inspired dose and uptake, and (3) uptake is more accurately described using a regression equation rather than by use of fractional uptakes.

ISSN:0098-4108    

DOI:10.1080/15287398909531272

出版商:Taylor & Francis Group    

年代:1989

数据来源: Taylor