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Biomedical subjects

R D Harbison

Publications and source records attributed to R D Harbison.

At least 73 records · Page 4Linked to original sources
PubMed1980

Halothane-induced hepatic necrosis in triiodothyronine-pretreated rats.

Hepatic centrilobular necrosis developed in rats pretreated with triiodothyronine (T3) and then anesthetized with halothane, 1 per cent, for two hours at an ambient oxygen concentration. Increasing oxygen concentrations decreased the severity of the lesion, there being a significantly (P less than 0.05) less severe lesion with oxygen, 99 per cent, as compared with 21 per cent. Pretreatment with phenobarbital alone resulted in hepatic necrosis only when hypoxia (FIO2 0.14) was also present, and there was no significant worsening of the T3-induced lesion when phenobarbital was added at any oxygen concentration studied. However, the lesion produced by T3 and oxygen, 14 per cent, was significantly worse than the lesion produced by phenobarbital and oxygen, 14 per cent. Glutamic pyruvic transaminase (SGPT) was significantly elevated to 776 (+/- 226) U/1 in the T3-treated rats (10 mg/kg/day, orally) immediately after halothane anesthesia. There was a significant decrease in glutathione to 1.48 (+/- 0.06) mg/g liver 24 hours after T3 administration (1 mg/kg subcutaneously for five days), but no further decrease with continued T3 pretreatment or with halothane anesthesia. Pretreatment with T3 caused a significant decrease in cytochrome P-450 to 0.41 (+/- 0.01) nmol/mg microsomal protein, and halothane anesthesia caused a further significant decrease to 0.27 (+/- 0.04) nmol/mg microsomal protein. The mechanism for the hepatic toxicity of halothane in this model remains to be determined.

Alanine Transaminase↗
PubMed1980

Regulatory role of glutathione and soluble sulfhydryl groups in the toxicity of adriamycin.

Adriamycin (ADR) has been shown to produce free radicals in NADPH microsomal systems, to increase oxygen consumption of both hepatic microsomes and heart sarcosomes and to stimulate superoxide formation in cardiac, submitochondria particles. These reactive products could produce the cardiotoxicity of ADR by oxidizing various membrane structures, especially if the heart lacks sufficient protective reducing substances such as thiols. We examined 1) the effect of ADR on reduced glutathione (G-SH) levels in various tissues including heart, 2) the ability of the sulfhydryl (SH) donor, cysteamine, to alter soluble SH levels in heart tissue after ADR administration and 3) the effects of SH donors (cysteamine and N-acetyl cysteine and G-SH depletion by diethyl maleate on ADR-induced lethality in Swiss ICR-HA mice. A single injection of ADR (15 mg/kg i.p.) elicited a statistically significant fall in liver (P < .05), heart (P < .02) and erythrocyte (P < .01) G-SH levels. Treatment with cysteamine protected against the fall in soluble SH groups in heart tissue. Cysteamine (50 mg/kg, i.p., every 8 hr for 6 days) or N-acetylcysteine (100 mg/kg, i.p., 1 hr before and 7 hr after ADR) protected against ADR-induced lethality and decreased the appearance of microscopic myocardial lesions. When endogenous levels of G-SH were depleted by diethyl maleate (300 mg/kg i.p., every 8 hr for 4 days), ADR lethality was markedly potentiated. Diethyl maleate alone did not cause death. We conclude 1) ADR significantly lowers G-SH levels in erythrocytes, liver and heart tissue, 2) the lowering of cardiac SH groups by ADR can be prevented by cysteamine and 3) ADR toxicity can be potentiated by diethyl maleate, a G-SH depletor, and reduced by cysteamine or N-acetyl cysteine, SH donors. These results suggest that the G-SH system may be involved in the modulation of ADR-induced toxicity.

Animals↗
PubMed1979

Metabolism and distribution of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in pregnant mice.

Pregnant mice were treated with a single oral dose of [carboxy-14C]2,4,5-T (100 mg/kg; 1.22 mu Ci/mg) on day 12 of gestation and sacrificed after 0.25, 0.5, 2 and 24 hours. Maternal blood, embryos, placentas and yolk sacs were analyzed by solvent extraction, TLC, and countercurrent distribution. Expressed as percentage of the administered dose/g tissue, the unchanged 2,4,5-T found in maternal blood, placentas, yolk sacs, and embryos was 3, 0.5, 0.5, and 0.2%, respectively, after 0.25 hours, and 4, 2, 2, and 0.5%, respectively, after 24 hours. No major metabolites of 2,4,5-T were detected. Urine and feces were also collected and analyzed. Radioactivity was largely eliminated in the urine, 69-78% of the administered dose in 7 days. Feces contained 5-9% of the dose. In the urine unchanged 2,4,5-T accounted for 35-44% of the dose, and 22-23% as very polar material. Unchanged 2,4,5-T in the feces was 3-5% and 1-2% as polar material. 2,4,5-T administered to pregnant mice is largely distributed and eliminated as 2,4,5-T and very polar material.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1977

Micromethod for determination of meperidine in plasma.

A GLC method utilizing a flame-ionization detector is described for the analysis of meperidine in blood plasma. Meperidine is extracted with ether from plasma that has been made basic with sodium hydroxide. The ether extract is evaporated to dryness, and the residue is dissolved in carbon disulfide for GLC analysis. An internal standard, N',N'-diethylaminoacetyl-2,6-xylidine, is used to quantitate meperidine. The extraction efficiency from plasma is 85%, and as little as 0.05 microng of meperidine can be quantitatively determined in 1 ml of plasma.

Chromatography, Gas↗
PubMed1977

Synthesis of 5-substituted 2-oxazolidinethiones and their antagonism to uterotropic effect of diethylstilbestrol.

5-(4-Aminophenoxymethyl)-2-oxazolidinethiones were synthesized by the cyclization of 1-(4-aminophenoxy)-3-amino-2-propanol in the presence of potassium hydroxide and carbon disulfide. This oxazolidinethione, on reaction with suitable isothiocyanates, yielded 5-[4-(substituted thiocarbamido)phenoxymethyl]-2-oxazolidinethiones. These compounds antagonized the uterotropic effects of diethylstilbestrol in female rats and possessed approximate LD50 values of 400-greater than 800 mg/kg.

Animals↗
PubMed1977

GLC microanalyses of phenacetin and acetaminophen plasma levels.

A GLC method utilizing a flame-ionization detector is described for the simultaneous analysis of acetaminophen and phenacetin in plasma. p-Bromoacetanilide is used as an internal standard. The drugs are extracted with ether from plasma diluted with 1 M phosphate buffer (pH 7.4). The ether extract is evaporated to dryness under nitrogen, and the residue is dissolved in 300 microliter of ethyl acetate. The ethyl acetate is transferred to a microcentrifuge tube (0.4 ml), and the sample is evaporated in a vacuum centrifuge. Then the residue is redissolved in 0.2 M trimethylanilinium hydroxide in methanol for GLC analysis. Extraction efficiency of added phenacetin and acetaminophen in plasma at concentrations of 1-10 microgram/ml was complete, and the limit of detection in plasma was less than 0.1 microgram.

Acetaminophen↗
PubMed1977

Alteration of delta 9-tetrahydrocannabinol-induced teratogenicity by stimulation and inhibition of its metabolism.

Treatment of pregnant mice with delta 9-tetrahydrocannabinol (THC) significantly increased the incidence of in utero deaths. SKF-525A pretreatment increased the incidence of THC-induced in utero deaths. THC also significantly reduced the body weight of surviving fetuses. Phenobarbital treatment antagonized THC-induced reduction of fetal body weight, but did not reduce resorption rate. Administration of THC, 50 or 200 mg/kg, did not induce fetal anomalies. However, both SKF-525A and phenobarbital treatment potentiated THC-induced cleft palates. SKF-525A treatment plus THC produced 36% cleft palates. Phenobarbital treatment plus THC produced 77% cleft palates. Pretreatments altered the level of tetrahydrocannabinol plus metabolites found in plasma, placenta, fetus and amnionic fluid. In general, SKF-525A increased levels and phenobarbital decreased levels. Two chemically reactive metabolites of THC are proposed, 9,10-epoxyhexahydrocannabinol and an 11-oxo derivative. SKF-525A pretreatment increased the concentration of both of these metabolites. Phenobarbital treatment increased the levels of the proposed 9,10-epoxyhexahydrocannabinol. Possible covalent binding of THC was observed. An active metabolite theory may apply to the teratogenic properties of THC.

Amniotic Fluid↗
PubMed1976

Stimulant actions of delta9-tetrahydrocannabinol in mice.

delta9-Tetrahydrocannabinol (THC) augments the locomotor activity produced by methamphetamine (0.5 mg/kg) in aggregated mice. THC-induced augmentation was dose related and lasted for a two-hour period. Maximal effective dosage of THC was 15 mg/kg with higer dosages of 30 and 60 mg/kg producing a decrease from maximum in locomotor activity. THC, 15 mg/kg, also increases locomotor activity among aggregated animals treated with saline. However, the increase was much less than the methamphetamine augmentation. In similar studies using isolated mice THC produced only a dose-related decrease in locomtor activity among both methamphetamine-treated and saline-treated animals. THC, 60 mg/kg, had no effect on methamphetamine-induced lethality in aggregated mice. However, at 15 mg/kg, THC significantly enhanced the lethality of methamphetamine. THC did not alter methamphetamine lethality in isolated mice. Distribution studies using 14C-methamphetamine indicated that neither THC nor isolation of animals affected tissue concentration or disappearance of 14C material. Previously reported synergistic interaction between amphetamine and THC is related to aggregation of the animals rather than drug treatment. Since THC at low doses can stimulate motor activity in saline-treated animals, amphetamine may act only to amplify the behavioral activity produced by low doses of THC.

Animals↗