Estrogenic induction of uterine arginase activity.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
J J Freeman
Publications and source records attributed to J J Freeman.
On the mechanism of amphetamine potentiation by iprindole.
Explore the source record for details and available documents.
Amines↗
Effect of hydroxyurea and related compounds on HMC mammary tumor growth and nucleic acids in Fischer rats.
Explore the source record for details and available documents.
Animals↗
Interpretation of restricted diffusion in sandstones with internal field gradients.
We report on experiments to characterize internal magnetic field gradients that are caused by magnetic susceptibility differences between the solid phase and the fluids filling the pore space. Our measurements focus on low-field relaxometry of brine and oil in sandstones from various reservoirs around the world. Our results show the need to understand the dependence of internal field gradients on diffusion length, pore size- and fluid distribution in order to predict the impact of internal gradients on the interpretation of NMR experiments.
Diffusion↗
Two-generation reproduction studies in Rats fed di-isodecyl phthalate.
Di-isodecyl phthalate (DIDP) is a commercial plasticizer with low toxicity in many animal studies. The effects of dietary DIDP administration on fertility and developmental parameters were assessed in Sprague-Dawley rats utilizing two generation reproductive toxicity studies generally consistent with current regulatory guidelines. Dietary levels ranged from 0.02 to 0.8% (or approximately 15 to 600 mg/kg/day). In the reproductive studies, there were no effects on fertility, but there were decreases in adult body weight along with corresponding increases in liver and kidney weights and histopathologic changes indicative of peroxisomal proliferation. There were no effects on live birth index, but reduced offspring survival was observed at postnatal days 1 to 4. This reduced survival was more pronounced in the F2 generation in which statistical significance was achieved at levels of 0.2% DIDP and greater. There were also transient decreases in offspring body weights prior to weaning, corresponding to rapid offspring growth, and high levels of food consumption. There were no notable alterations in developmental landmarks. Overall, these studies provided experimentally defined No-Observed-Adverse-Effect Levels (NOAELs) of 0.06% (approximately 50 mg/kg/day) for F2 offspring survival and 0.8% (approximately 600 mg/kg/day) for fertility, other measures of reproductive function, and developmental landmarks. Statistical evaluation of the data from both studies identified 108 mg/kg/day with a 95% lower bound value of 86 mg/kg/day as a theoretical NOAEL for reduced F2 offspring survival.
Animals↗
Two-generation reproduction study in rats given di-isononyl phthalate in the diet.
The potential reproductive toxicity of di-isononyl phthalate (DINP: CAS RN 68515-48-0) was assessed in one- and two-generation reproductive toxicity studies. Groups of 30 male and female CRL : CD(SD)BR rats were given DINP via dietary administration at levels of either 0.0, 0.5, 1, or 1.5% (one-generation study) or 0.0, 0.2, 0. 4, or 0.8% (two-generation study). There were no changes in any of the classic reproductive parameters, i.e. mating, male or female fertility, fecundity, gestational index, or length of gestation in either study. The overall NOAELs for these effects were the highest Dietary Level (%)s tested, approximately 500 mg/kg/day in the two-generation study and 1000 mg/kg/day in the one-generation study. There were no testicular effects in parental animals exposed as juveniles and young adults at 960 mg/kg/day in the one-generation study. In the two-generation study, there were no testicular effects in either the P(1) males, exposed as juveniles and young adults or the P(2) (F(1)) offspring exposed in utero, through lactation, and continuously to terminal sacrifice. The NOAEL was 470 mg/kg/day. Offspring survival was reduced at the 1.5% level ( approximately 1100 mg/kg/day) but unaffected at the 1% level ( approximately 760 mg/kg/day). There were decreased offspring body weights both at postnatal day (PND) 0 and during lactation; however, the PND 0 effects were only clearly related to treatment at the 1.5% level. Weights of offspring during lactation were significantly reduced but within the historical control range at Dietary Level (%)s below 1%. As there was rapid recovery at the lower levels, even though treatment continued, the toxicologic significance is unclear. Adult survival was unaffected at any level in either study, but weight gain was significantly reduced at the 1% level ( approximately 600 mg/kg/day). Liver and kidney weights were elevated at Dietary Level (%)s above approximately 110 mg/kg/day, consistent with evidence from other studies of peroxisomal proliferation at these levels. This study showed that DINP treatment does not affect fertility or male reproductive development at doses of up to approximately 1000 mg/kg/day.
Animals↗
Benzyl carbamyl analogue of lignocaine: vasodepressor mechanism of action.
1. The benzyl carbamyl analogue of lignocaine [2-(diethylaminoacetamido)-3-carbamyl-4-methyl-5-benzylpyrrole] at an intravenous dose of 4 mg/kg caused a blood pressure decrease of 54 mmHg. 2. A greater hypotensive effect was observed in hypertensive compared to normotensive animals. Anaesthesia magnified the vasodepressor effect in both groups. 3. The analogue did not possess centrally-mediated effects on blood pressure but exerted its hypotensive effect via a peripheral mechanism. 4. The analogue produced a relaxant effect on intestinal and vascular smooth muscle while exerting minimal effects on muscarinic, sympathetic, or ganglionic nicotinic receptors. 5. The analogue exhibited less cardiac depressant action on left ventricular rate (dp/dt) and force of contraction than lignocaine. 6. Lethal effects for the analogue were first observed at 16 mg/kg following intravenous administration and at 500 mg/kg following intraperitoneal administration. 7. In conclusion, the benzyl carbamyl analogue exhibited direct vascular smooth muscle relaxant activity with less cardiac or CNS side effects than lignocaine.
Anesthesia↗
Comparative 90-day feeding study with low-viscosity white mineral oil in Fischer-344 and Sprague-Dawley-derived CRL:CD rats.
A 90-day study was conducted to compare the effects of dietary administration of a food-grade white oil in female Fischer-344 (F-344) and Sprague-Dawley-derived (CRL:CD) rats. Animals were fed a low viscosity (15 mm2/sec at 40 degrees C) paraffinic white oil (designated as P 15[H]) at 0, 0.2, or 2.0% of the diet for 30, 61, or 92 days. There were no significant adverse clinical observations or unscheduled deaths. In the F-344 rats, occasional treatment-related changes were seen in hematology and clinical chemistry parameters. At necropsy, mesenteric lymph nodes were enlarged, and there was an increase in absolute and relative liver, mesenteric lymph node, and spleen weights as compared to controls. Histopathologic effects included hepatic and mesenteric lymph node microgranulomas and mesenteric lymph node histiocytosis. In CRL:CD rats, the only effects noted were accumulations of chronic inflammatory cells in the liver at the high dose only, without the formation of discrete microgranulomas. A dose-related increase in mineral hydrocarbon (MCH) material in the liver and mesenteric lymph nodes was observed in both F-344 and CRL:CD rats. Although increased, liver MhC content was significantly less (approximately 50%) in CRL:CD rats than the levels detected in the F-344 rats. Mesenteric lymph node MHC levels did not differ significantly between the strains. This study demonstrated strain differences among rats in histopathologic effects of white oil, with the CRL:CD rat essentially showing no response compared to the F-344 rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
A 90-day toxicity study of the effects of petroleum middle distillates on the skin of C3H mice.
Petroleum middle distillates (PMDs) elicit skin tumors in mouse epidermal carcinogenesis studies. The response is characterized by a long latency with only a small percentage of animals developing tumors. Although the carcinogenic activity of certain other petroleum hydrocarbons largely depends upon the presence of polycyclic aromatic hydrocarbons (PAHs), many PMDs contain relatively low concentrations of PAHs. PMDs are also irritating to mouse skin, and chronic irritation may be involved in the development of skin tumors. This study was conducted to investigate the patterns of cutaneous irritation elicited by topical application of PMDs having compositional differences. The three PMDs selected for study were a steam cracked gas oil (SCGO), a lightly refined paraffinic oil (LRPO), and a jet fuel (JF). Male C3H/HeNCr1BR mice (25/group) were treated topically (37.5 microliters 2x/week for 13 weeks) with 10%, 50% or 100% (undiluted) concentrations of each PMD. Catalytically cracked clarified oil (CCCO, 10%), a potent carcinogen to mouse skin, was also tested. The vehicle was a noncarcinogenic mineral oil with a viscosity of 90 SUS. Cutaneous changes were evaluated by gross observations and light microscopy. Cutaneous irritation was the only significant toxic response in this study. Neither the vehicle nor any of the 10% PMD concentrations produced significant cutaneous irritation. The 10% CCCO and 50% PMD treatments all elicited slight to moderate proliferative and inflammatory changes in mouse skin. Ulcers were also observed microscopically in mice treated with 10% CCCO and 50% SCGO. The 100% SCGO treatment produced evidence of necrosis on Days 1-7 but not later in the study despite continued treatment. In contrast, the irritating effects of 100% LRPO were not evident until 2-3 weeks of study, and at study completion were characterized by moderately severe inflammatory and proliferative changes. The effects of 100% JF were qualitatively similar to 100% LRPO but less marked. Thus, the SCGO caused a different pattern of cutaneous responses than either LRPO or JF. The possible relationships of these cutaneous changes to epidermal carcinogenesis are being studied further.
Animals↗
Hantavirus pulmonary syndrome associated with Monongahela virus, Pennsylvania.
The first two recognized cases of rapidly fatal hantavirus pulmonary syndrome in Pennsylvania occurred within an 8-month period in 1997. Illness in the two patients was confirmed by immunohistochemical techniques on autopsy material. Reverse transcription-polymerase chain reaction analysis of tissue from one patient and environmentally associated Peromyscus leucopus (white-footed mouse) identified the Monongahela virus variant. Physicians should be vigilant for such Monongahela virus-associated cases in the eastern United States and Canada, particularly in the Appalachian region.
Adult↗