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Biomedical subjects

M Gosálvez

Publications and source records attributed to M Gosálvez.

At least 19 recordsLinked to original sources

Carcinogenesis with the insecticide rotenone.

Rotenone is an insecticide which has been used extensively for a long time, and is now widely used in the U.S.A. and other industrialized countries. Rotenone is used mainly as an agricultural insecticide, household garden insecticide and water plant pesticide. Through these uses, rotenone may now be reaching the human male and female in these countries in substantial amounts, carried by fresh or cooked vegetables, consumed fish and drinking water. A review of the existing published reports and unpublished official documents dealing with the capacity of rotenone to induce neoplastic, paraneoplastic and preneoplastic lesions in the rat is presented here. It is strongly suggested that rotenone is carcinogenic to the rat (at doses from 2 to 25 parts per million continuously in food, or from 0.8 to 2.5 mg/kg weight for 1 to 4 months by oral administration), above all, when the rats receive deficient diets, especially those poor in riboflavin. Rotenone carcinogenesis, among other things, seems to exhibit a peculiar dose response pattern, which could be explained by its possible hormonal mechanism of action. Further studies to assess definitively the role of rotenone as a possible environmental carcinogen are proposed as being highly necessary.

Animals↗

Thioproline.

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Administration, Oral↗

Quelamycin: a summary of phase I clinical trials.

Quelamycin is triferric doxorubicin, a metallic derivative of adriamycin which, in experimental studies, has been found to have a better therapeutic index than adriamycin and no cardiotoxicity. In Spain, phase I clinical trials carried out in 96 patients with advanced cancer have shown that the drug has low toxicity and considerable antitumor activity, while it is not cardiotoxic, even at cumulative doses of nearly 3 g.

Adolescent↗

Inhibition of sodium-potassium-activated adenosine 5'-triphosphatase and ion transport by adriamycin.

The antitumor antibiotic Adriamycin is a potent inhibitor of the sodium-potassium-activated adenosine triphosphatase of native heart microsomes. Adriamycin also inhibits potassium transport (although not sodium transport) in slices of kidney cortex. The effects on both the adenosine triphosphatase and ion transport are markedly reduced by Ca2+, probably by chelation of this metal by Adriamycin. These effects could provide a basis for explaining the Adriamycin cardiotoxicity as a digitalis-type toxicity.

Animals↗

Early clinical trial with quelamycin.

Quelamycin (triferric doxorubicin) is a derivative of Adriamycin with different pharmacologic properties. Our phase I clinical study of quelamycin includes 37 patients with a wide spectrum of solid tumors. The recommended dose in good-risk patients is 150 mg/m2, given as a 1-hour infusion every 3 weeks. The dose-limiting factor appears to be myelosuppression, especially leukopenia. Other toxic effects include gastrointestinal intolerance and alopecia. Chills and fever are commonly encountered and might be due to an excess of free iron in currently available preparations. Cardiotoxicity could not be properly assessed. An objective antitumor effect was seen in patients with lung, gastric, colon, and ovarian carcinomas as well as osteogenic sarcoma. Further preclinical and clinical studies with an improved pharmaceutic formulation of the drug are highly desirable.

Adolescent↗

Spectral and metabolic characteristics of mitochondrial fractions from rotenone-induced tumours.

Mitochondrial fractions isolated from tumours induced with the respiratory inhibitor rotenone lack respiratory control, oxidative phosphorylation, are partially or totally insensitive to cyanide and have a near-normal content of respiratory carriers. These characteristics are more similar to those of mitochondria from atrophic mammary gland than to those of mitochondria from spontaneous mammary adenomas. Thus, the characteristic structural and biochemical mitochondrial alteration of rotenone-induced tumours would represent a lack of mitochondrial differentiation as the tumour develops from the atrophic mammary gland. Slices of rotenone-induced tumours are insensitive to oligomycin and dinitrophenol, thus indicating that glycolysis would be their sole source of metabolic energy.

Adenofibroma↗

Mitochondrial functions and content of microsomal and mitochondrial cytochromes in human cirrhosis.

1. Mitochondria and microsomal fractions have been isolated from liver biopsies from patients with alcoholic cirrhosis, cryptogenic cirrhosis or chronic aggressive hepatitis. 2. Cirrhotic livers yieled fewer mitochondria than normal liver. 3. The most significant change was a decrease in mitochondrial respiratory control. Cirrhotic microsomal fractions had a 50% diminution in cytochrome b5 and cytochrome P-450 content. 4. The two patients with chronic aggressive hepatitis showed similar mitochondrial and microsomal changes.

Adult↗