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Biomedical subjects

R T Louis-Ferdinand

Publications and source records attributed to R T Louis-Ferdinand.

17 recordsLinked to original sources

Diminished mephobarbital anticonvulsant action following diphenhydramine pretreatment.

Diphenhydramine and other antihistamines produce biphasic effects on drug disposition and lower seizure threshold, thereby potentially diminishing the efficacy of anticonvulsants such as mephobarbital. Accordingly, the influence of diphenhydramine (50 mg/kg, IP) pretreatment on the anticonvulsant activity of mephobarbital (50 mg/kg, IP) was determined in adult female Swiss-Webster mice given pentylenetetrazol (SC). Diphenhydramine lowered the pentylenetetrazol convulsive dose (CD50) by 60%. Administration of diphenhydramine in combination with mephobarbital produced a 65% decrease in the CD50 of pentylenetetrazol in comparison with that of animals given mephobarbital plus pentylenetetrazol. Pharmacokinetic evaluation of mephobarbital blood level data indicates that the mechanism responsible for the observed interaction between diphenhydramine and mephobarbital involves a decrease in mephobarbital uptake from the administration site.

Animals

Erythrocyte pyrimidine 5'-nucleotidase inhibition by acute lead exposure in neonatal rats.

Inhibition by lead of erythrocyte pyrimidine 5'-nucleotidase (P5N) is thought to contribute to morphological abnormalities observed in red blood cells (RBC) of lead-exposed subjects. However, neither the mechanism of lead inhibition of P5N nor the relationship of this inhibition to blood lead levels attained in exposed subjects is known. In the present investigation, acute in vivo and in vitro lead acetate effects on erythrocyte P5N from 21-day-old rat pups were determined and were related to blood lead concentrations ascertained by atomic absorption spectrophotometry. Acute lead administration to rat pups resulted in a 16% to 21% reduction in erythrocyte P5N, with mean blood lead levels ranging from 77 to 108 micrograms/dl 24 hours later. Inhibition of erythrocyte P5N was linearly related to blood lead level (r = -0.67, P less than 0.05) following acute lead administration. Lead acetate addition to RBC preparations from 21-day-old rats resulted in concentration-dependent P5N inhibition which was comparable to that produced following acute in vivo exposure. The results indicate that acute P5N inhibition in lead-treated neonatal rats is due to noncompetitive P5N inhibition by lead. The inhibition of P5N produced by acute lead treatment is linearly related to blood lead concentrations.

5'-Nucleotidase

Discriminative stimulus properties of amphetamine and other stimulants in lead-exposed and normal rats.

The present study examined the discriminative stimulus properties of amphetamine (AMP) at progressively lower doses in lead-exposed and normal rats. In addition, generalization gradients of AMP, apomorphine, methylphenidate, and caffeine to both high and low training doses of AMP were determined in these rats. Under the high AMP training dose condition (1.0 mg/kg, IP) generalization gradients of AMP were similar for lead-exposed and control rats. When the training doses were progressively lowered, the lead-exposed rats tended to require a higher range of AMP doses (0.24-0.49 mg/kg) than did control rats (0.18-0.32 mg/kg) to maintain discriminative control. In parallel with this, the minimal discriminable doses tended to be higher for lead-exposed rats than for control rats. Methylphenidate generalization gradients were different for lead-exposed and control rats under the high AMP training condition but became similar under the low AMP training condition. No differences attributable to training dose or lead exposure were evident for apomorphine or caffeine.

Amphetamine

Age of testing as a factor in the behavioral effects of early lead exposure in rats.

The behavioral effects of postnatal administration of lead during weaning were tested in young and adult rats. Rats received either 10 mg/kg IP lead acetate or equimolar sodium acetate daily for the first twenty days of life. Tests of performance on an 8-arm radial maze and a passive avoidance task were begun at 25 days after birth or 90 days after birth. Lead-treated rats did not perform significantly different than control rats on the radial arm maze at either age tested. Young lead-treated rats performed with significantly longer lick latencies than young control rats on the passive avoidance task. Adult lead-treated rats performed with shorter food latencies than adult control rats. A group of young rats was retested on the passive avoidance task at 150 days after birth. Performance on the retest was similar to their early performance. Differences in performance of young and adult lead-treated animals on the passive avoidance task are discussed in terms of an interaction of the effects of lead exposure, maturation, and early experience.

Age Factors

Differential effects of folic acid on water content, protein and microsomal 5'-phosphodiesterase activity of the rat kidney.

The effects of folic acid administration on the weight, protein, water content and microsomal 5'-phosphodiesterase of the rat kidney were determined, to elucidate the mechanisms contributing to the renal enlargement produced by this agent. Folic acid administered ip in single doses of 100-250 mg/kg caused dose-related increases in kidney weight, water and protein content within 24 hr. Time-course studies indicated that 250 mg folic acid/kg given ip produced a progressive elevation in renal water content from 2 to 72 hr. Smaller increases in whole-kidney protein were recorded 8, 24 and 72 hr after folic acid treatment. However, a biphasic response of microsomal 5'-phosphodiesterase was produced, inhibition at 16 hr being followed by stimulation (to 140% of control) at 72 hr. In vitro studies indicated that folic acid inhibits 5'-phosphodiesterase competitively, and the early inhibition of 5'-phosphodiesterase in vivo appears to be due to a direct effect of folic acid on the enzyme.

Animals

Effect of lead acetate on the kinetics of gamma-glutamyl transpeptidase activity from neonatal rat pup brain.

The objective of the present investigation was to determine the influence of lead acetate on kinetic parameters of gamma-Glutamyl Transpeptidase (GGT) in brain homogenates from 15 and 30 day old rat pups. Determinations of maximal velocity (Vmax) indicated that the Vmax of GGT from 15 day old pups was 58% of that from 30 day old animals while negligible differences in apparent Km were observed between either group. Addition of lead acetate to GGT preparations from 15 day old pups produced no significant changes in apparent Km for gamma-Glutamyl-p-Nitroanilide (GPNA). However, Vmax was decreased to 35% of control. Addition of lead acetate to GGT incubations from 30 day old pups produced negligible changes in apparent Km for GPNA while Vmax was decreased to 71% of control activity. These data indicate that lead acetate inhibits brain GGT activity from both groups noncompetitively and that brain GGT from 15 day old rats is more susceptible to lead than is that from 30 day old animals.

Animals

P-Chloro-N-methylaniline demethylation by rat kidney subcellular fractions.

Subcellular fractions prepared from kidney homogenates catalyzed the demethylation of p-chloro-N-methylaniline (PCMA). The activity of the renal preparations were forty-one percent of the liver 9,000 xg supernatant fraction activity. A differential susceptibility to the addition of carbon monoxide, p-chloromercuribenzoate or the omission of NADPH and magnesium characterized the two preparations. Comparison of the Lineweaver-Burk plots of the PCMA demthylation activities indicated that the maximal velocities and the apparent Michaelis constants (Km) of the two preparations differed. The apparent Km of the renal enzyme was approximately two fold greater than that of the liver. The PCMA demethylation activity of renal preparations is distributed between the cytosol and microsomal subcellular fractions. The results suggest the presence of tissue-related differences between renal and hepatic enzymes which catalyze the demethylation of PCMA.

Aniline Compounds