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Biomedical subjects

G Powis

Publications and source records attributed to G Powis.

At least 199 records · Page 11Linked to original sources
PubMed1981

Protection against adriamycin-induced skin necrosis in the rat by dimethyl sulfoxide and alpha-tocopherol.

Extravasation of Adriamycin during i.v. infusion can cause serious local complications. We have used a rat skin model to study the protection afforded by dimethyl sulfoxide and alpha-tocopherol (vitamin E) against Adriamycin-induced skin necrosis. Topical daily application of 1 ml dimethyl sulfoxide for 2 days produced a small decrease in ulcer diameter of up to 11% at 2 weeks. Topical daily applications of 1 ml 10% alpha-tocopherol succinate in dimethyl sulfoxide for 2 days produced a marked decrease in ulcer diameter at 2 weeks of up to 68%. Daily topical application of 1 ml 10% alpha-tocopherol succinate in dimethyl sulfoxide for 7 days offered no greater protection than 2-day application. alpha-Tocopherol acetate appeared to have activity slightly less than that of alpha-tocopherol succinate in reducing ulcer size, and both compounds were considerably more active than was alpha-tocopherol alcohol. Administration of alpha-tocopherol succinate or alpha-tocopherol acetate i.p. had no significant effect upon ulcer diameter. Topically applied dimethyl sulfoxide and alpha-tocopherol may provide an effective way of treating accidentally extravasated Adriamycin in cancer patients.

Administration, Topical↗
PubMed1981

Protection by alpha-tocopherol and dimethylsulfoxide (DMSO) against adriamycin induced skin ulcers in the rat.

Extravasation of adriamycin during intravenous infusion to cancer patients can cause serious local complications. Topical application of 1 ml 10% alpha-tocopherol succinate in DMSO for 2 or 7 days produced up to a 71% decrease in the diameter of skin ulcers produced by intradermal adriamycin in the rat. A combination of alpha-tocopherol and DMSO might be useful for protecting humans against accidentally extravasated adriamycin.

Administration, Topical↗
PubMed1980

N-Oxide reduction by hemoglobin, cytochrome C and ferrous ions.

Indicine N-oxide is reduced to indicine by Fe(II) ions, by enzymatically reduced cytochrome c, and by ascorbic acid in conjunction with hemin or cytochrome c. Indicine N-oxide is not reduced by native hemoglobin, but is reduced by denatured hemoglobin. Oxygen competes with indicine N-oxide for reduction by denatured hemoglobin.

Antineoplastic Agents, Phytogenic↗
PubMed1979

Determination of L-alanosine in plasma and urine by reversed-phase high-performance liquid chromatography of the Dns derivative.

L-Alanosine is an antitumour antibiotic that has recently been placed in clinical trial. We have developed a relatively rapid and specific assay for urinary and plasma alanosine, based on formation of the Dns derivative and separation of this from other Dns compounds by reversed-phase high-performance liquid chromatography. Dns-Alanosine is detected by its absorption at 254 nm, since alanosine is atypical in that it forms a Dns derivative with very low fluorescence. The lower limit of detection of alanosine in plasma is 0.1 microgram/ml. The assay has been used to measure the levels of alanosine in the plasma and urine of rabbits and of man.

Alanine↗
PubMed1979

Disposition and metabolism of pentamethylmelamine and hexamethylmelamine in rabbits and humans.

The disposition and metabolism of pentamethylmelamine (PMM) and hexamethylmelamine (HMM) were studied in the rabbit, and the disposition of PMM was studied in humans. Parent compound and metabolites were identified by thin-layer chromatography, gas chromatography, and gas chromatography/mass spectrometry analyses. Plasma elimination in both species following i.v. administration of each drug was best described by a two-compartment open model. Both compounds were extensively demethylated with less than 1% of the total dose administered recovered in the urine over 24 hr. The areas under the plasma time-concentration curves of PMM and HMM following p.o. administration to rabbits were 5 and 25% of the areas following i.v. administration. Gastrointestinal absorption was rapid and efficient with 75 to 89% of drug equivalents recoverable in the urine after p.o. administration of [ring-14C]PMM or [ring-14C]HMM to rabbits. Reduced bioavailability of PMM and HMM p.o. appears to be a consequence of rapid metabolism presumably in the liver.

Altretamine↗
PubMed1979

Relationship of the reductive metabolism of indicine N-oxide to its antitumor activity.

Several pyrrolizidine alkaloids have been demonstrated to have antitumor activity in experimental tumor systems. In general the free base form of the alkaloid exhibits greater biological activity than the corresponding N-oxide and the N-oxide must be metabolized to the base for the subsequent formation of alkylating intermediates. Indicine N-oxide is an exception in that it is a more active antitumor agent than its free base indicine. Studies of the antitumor activity and metabolism of indicine N-oxide, and the closely related compound, heliotrine N-oxide, given orally and intraperitoneally to mice bearing P-388 leukemia, suggest that conversion of indicine N-oxide to indicine is not essential for its antitumor activity.

Anaerobiosis↗
PubMed1979

Metabolic conversion of indicine N-oxide to indicine in rabbits and humans.

Indicine N-oxide, a pyrrolizidine alkaloid N-oxide that exhibits antitumor activity without some of the toxic effects associated with other pyrrolizidine alkaloids, is metabolized to indicine in rabbits and humans. Indicine can be detected in the plasma and is excreted in the urine in a dose-dependent manner following the i.v. administration of indicine N-oxide. The p.o. administration of indicine N-oxide leads to an increased plasma concentration and an increased urinary excretion of indicine. The hepatic microsomal fraction and the gut flora both catalyze the anaerobic reduction of indicine N-oxide to indicine in vitro. Whole-animal studies suggest that the gut flora play a major role in the metabolic reduction of indicine N-oxide by the rabbit. Indicine N-oxide is not actively excreted in the bile, and it is probable that indicine N-oxide finds its way into the gut by passive diffusion following i.v. administration. Neomycin and erythromycin, which reduce the number of anaerobic bacteria in the gut, lead to decreased plasma levels and a decreased urinary excretion of indicine.

Animals↗
PubMed1978

Determination of indicine N-oxide and indicine in plasma and urine by electron-capture gas-liquid chromatography.

A sensitive and specific method is described for the quantitative analysis of indicine N-oxide and indicine in plasma and urine. Indicine N-oxide is reduced to the tertiary amine with zinc--acetic acid (plasma) or zinc--ammonium chloride (urine). The indicine is derivatized with pentafluoropropionic anhydride to provide electron-capture detection. Assay of rabbit and human plasma and urine samples can detect 100 ng/ml (plasma) and 200 ng/ml (urine), and the method was applied to the analysis of indicine N-oxide and indicine in rabbits and one patient following administration of indicine N-oxide.

Animals↗