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Biomedical subjects

R R Humphrey

Publications and source records attributed to R R Humphrey.

34 records · Page 2Linked to original sources
PubMed1975

Stimulation of LH release and ovulation in the rat by cutaneous application of luteinizing hormone-releasing hormone (LH-RH) in dimethyl sulfoxide (DMSO).

The efficacy of cutaneously applied luteinizing hormone releasing hormone (LH-RH) in stimulating LH release in the chronically ovariectomized, estrogen/progesterone-blocked rat and ovulation in the chlorpromazine-blocked, proestrous rat was investigated. Following the cutaneous application of 25 or 100 mug of LH-RH in 100% dimethyl sulfoxide (DMSO), serum LH rose to a peak at 1 hr, then declined toward basal levels in the ensuing 3 to 4 hr. LH-RH applied cutaneously in either 100% DMSO or 0.9% NaCl was also capable of inducing ovulation in the chlorpromazine-blocked, proestrous rat; however, LH-RH in 0.9% NaCl did not yield a linear log-dose-response relationship, therefore a valid ED50 potency ratio for DMSO/0.9% NaCl could not be estimated. Nonetheless, 0.9% NaCl was a considerably less effective cutaneous vehicle than DMSO. Cutaneous application of LH-RH in DMSO in doses of 100, 50, 25, 10, 5, 2.5 and 1 mug induced ovulation in 100%, 100%, 90%, 73%, 30%, 10% and 0% of the rats, respectively. When the percent ovulation response was transformed to probits and plotted against the logarithm of the LH-RH dose an approximately linear log dose-response was obtained; the same relationship also held true for ovulation induction following sc LH-RH administration. In turn, the ED50's of these two parallel dose-response curves yielded a potency ratio estimate (sc/cutaneous) of 0.025, suggesting that 2.5% of the cutaneously applied LH-RH dose was absorbed through the skin in a biologically active form. These data indicate that DMSO privdes a convenient cutaneous vehicle for the administration of LH-RH.

Administration, Topical↗
PubMedDate not supplied

Teratogenesis of calcium valproate in rats.

Studies were conducted to determine the teratogenic potential of the calcium salt of valproic acid in rats when given orally at doses of 600, 150, and 50 mg/kg on days 6--15 of gestation. The sodium salt of valproic acid was used as a reference agent at a dose level of 600 mg/kg. The administration of 600 mg/kg/day of either calcium or sodium valproate resulted in transient, severe sedation in the dams. Four dams receiving 600 mg/kg of either salt died during the experiment, with deaths occurring between day 7 and 11 of gestation. Food consumption and body weight gain were significantly reduced during the dosing period with both salts at dose levels of 600 mg/kg. Embryotoxicity at the high doses (600 mg/kg) with either salt was manifested by increases in fetal resorption, reduced body weights, and significantly increased incidence of supernumerary ribs and bifid vertebral centra among the surviving fetuses. A teratogenic effect was evident at 600 mg/kg with either salt of valproic acid. Seven of 16 fetuses from dams given the calcium salt were abnormal. Findings included one with omphalocele and six others with skeletal malformations. Eleven of 24 fetuses from dams given the sodium salt were abnormal: three littermates had bilateral ectrodactyly of the rear feet and malformed vertebral centra and eight others had skeletal malformations. No teratogenic effect was evident among the fetuses from dams given 150 mg/kg calcium salt. Embryotoxicity was demonstrated by a significant increase in the incidence of supernumerary ribs. No adverse effect was observed among the fetuses from dams given 50 mg/kg of the calcium salt.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

A lethal mutant gene in the Mexican axolotl.

Gene ph was discovered in a wild-type axolotl male received from Mexico City. Larvae homozygous for this gene become recognizable by their lighter color at hatching or shortly after. The development of their forelimbs is retarded, and all limbs are of subnormal length because of the reduction in length of their long bones. Many affected larvae die without feeding, and very few survive beyond their third month. At death, older larvae usually show abnormalities of the renal system, edema, ascites, or adhesions of the viscera. The gene is apparently a simple recessive with full penetrance.

Ambystoma↗