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Biomedical subjects

A B Combs

Publications and source records attributed to A B Combs.

34 records · Page 2Linked to original sources
PubMed1978

Rescue by coenzyme Q10 from electrocardiographic abnormalities caused by the toxicity of adriamycin in the rat.

The administration of adriamycin to rates increased (P less than 0.01) the interval, measured in msec, of the electrocardiographic QRS traces in rats, and the magnitude of the increase was ca. 50%. The administration of coenzyme Q10 to such adriamycin-treated rats allowed "rescue" or restoration of a normal QRS complex after 7 days of administration of coenzyme Q10. The QRS complex then remained normalized during the subsequent period of 21-30 days, by which time the cumulative dose of adriamycin had reached 24 mg/kg. Also, the QRS interval was lower (P less than 0.01) on day 33 than it was for rats treated to the same day with adriamycin alone. Coenzyme Q10 offers promise of rescue from at least some of the cardiotoxicity occurring in adriamycin-treated cancer patients, probably by a similar mechanism to that of the clinical rescue from toxicity of methotrexate by a cofactor of folic acid (citrovorum factor).

Animals↗
PubMed1978

Potentiation of the toxicity of adriamycin by propranolol.

Both propranolol and adriamycin are biochemically known to inhibit mitochondrial CoQ10-enzymes of myocardial tissue in vitro. Both propranolol and adriamycin are clinically known to cause cardiotoxicity. At two dose levels of propranolol which caused no deaths to mice when administered alone, significant potentiation (p less than 0.01) of the lethality of adriamycin to mice was observed. These data, projected to the clinical situation, seem to contraindicate the administration of the beta-blocker, propranolol, for the hypertension of a cancer patient who is being treated with adriamycin.

Animals↗
PubMed1977

In vitro photodecomposition of uric acid in presence of riboflavin II.

In vitro studies on the photodecomposition of uric acid in the presence of the monosodium salt of riboflavin 5'-phosphate in buffers at various pH values, in methanol, and in human plasma are reported. The decomposition rate increased with increasing pH and was independent of solvent or buffer species. The mechanism appears to be an energy transfer process involving triplet riboflavin and single oxygen. Riboflavin-enhanced photodecomposition of uric acid occurred in vitro in hyperuricemic human plasma.

Chromatography, High Pressure Liquid↗
PubMed1977

Reduction by coenzyme Q10 of the acute toxicity of adriamycin in mice.

Pretreatment for four days with coenzyme Q10 (COQ10) reduced the acute toxicity in mice treated with adriamycin. In two sequential protocols, adriamycin allowed only 36 and 42% survival, respectively. Pretreatment with COQ10 allowed 80 and 86% survival, respectively. The differences are significant, p less than 0.05. The mechanism for this reduction in the acute toxicity may be based upon the prevention by the supplementary COQ10 of the inhibition caused by adriamycin to COQ10-dependent enzymes in cardiac and and other tissues. The prospect of diminishing the toxicity of adriamycin in cancer patients remains promising and important.

Animals↗
PubMed1976

Anticoagulant activity of a naphthoquinone analog of vitamin K and an inhibitor of coenzyme Q10- enzyme systems.

Synthetic 2-hydroxy-3-h-dodecylmercapto-1,4-naphthoquinone is an analog of both vitamin K1 and coenzyme Q10. This naphthoquinone analog is an effective inhibitor of coenzyme Q10-enzymes of mammalian mitochondria, which are components of electron transfer mechanisms of respiration and coupled oxidative phosphorylation. This analog increased the prothrombin time in rats when it was administered orally or parenterally. Vitamin K1 reversed the prothrombin time increase, but that form of coenzyme Q, hexahydrocoenzyme Q4, which has the same phytyl side chain as vitamin K1, did not reverse the increase, constituting the biological differentiation between vitamin K and coenzyem Q. Two benzoquinone analogs of coenzyme Q10, 5-n-octadecylmercapto-2,3-dimethoxy-1,4-benzoquinone and 5-beta-naphthylmercapto-2,3-dimethoxy-1,4-benzoquinone, the latter being a strong inhibitor of coenzyme Q10-enzymes, did not increase the prothrombin time under comparable conditions.

Animals↗
PubMed1976

Models for clinical disease. I. Biochemical cardiotoxicity of a coenzyme Q10-inhibitor in rats.

The pharmacology and toxicity in animals of synthetic analogs of essential metabolites, which show in vitro antagonism of the metabolite, may point out pathology associated with a deficiency of the metabolite. On this basis, 2-hydroxy-3-n-dodecylmercapto-1,4-naphthoquinone, a potent in vitro inhibitor of a mitochondrial coenzyme Q10-enzyme, was administered to rats. The specific activities and the percent deficiencies of the succinate dehydrogenase-coenzyme Q10 reductase in cardiac mitochondria were significantly increased (0.001 less than P less than 0.01). These enzyme activities were unchanged in leucocytes and in the dorsal aorta. This biochemical cardiotoxicity of an antimetabolite of coenzyme Q10 adds to the advancing knowledge on coenzyme Q10 in cardiac metabolism and disease, and could correlate with the cardiotoxicity of the clinical antitumor drug, adriamycin.

Animals↗
PubMed1976

Effects of exercise training and exhaustion on 45Ca uptake by rat skeletal muscle mitochondria and sarcoplasmic reticulum.

Mitochondrial and sarcoplasmic reticular 45Ca2+ uptake and Ca2+-ATPase activity were determined in skeletal muscle from exercise trained and non-trained rats at rest or following short-term exhaustive exercise. In trained rats exercised to exhaustion, mitochondrial 45Ca2+ uptake was significantly depressed when compared to non-trained rats at rest. Ca2+-ATPase activity of sarcoplasmic reticulum from trained rats exercised to exhaustion was significantly increased as compared to trained rats at rest. These data suggest that the disruptive influence of Ca2+ accumulation in mitochondria isolated following exhaustive exercise may be diminished as a result of training.

Adenosine Triphosphatases↗
PubMed1975

The action of isoproterenol on phenylthiourea induced pulmonary edema.

Isoproterenol inhalation increases the pulmonary edema induced in rats by phenylthiourea. Propranolol decreases this response while phenoxybenzamine has no effect upon it. It is proposed that the observed increase in toxicity is related to the beta-adrenergic effects of the isoproterenol and that the specific mechanism responsible might be an increase in pulmonary capillary hydrostatic pressure which is secondary to an increase in pulmonary blood flow.

Aerosols↗
PubMedDate not supplied

Effect of formulation factors on the matrix pH of nylon microcapsules.

The application of nylon microencapsulation as a drug delivery system inherently demands that the microencapsulated matrix should not cause degradation of the encapsulated drug. The presence of alkaline hexamethylenediamine (HMD) in the microcapsule core will affect the final pH of the microcapsules and may influence the stability of some drugs. To follow the pH within the microcapsule core during manufacture, pH indicators were encapsulated. The final pH was found to depend on the formulation used and could be controlled by the addition of acid. Several other variables affecting the nylon wall formation were examined to determine optimum processing conditions. Increased agitation produced a decrease in microcapsule size. This cause an increase in nylon weight recovered. The increased recovery of nylon was due in part to nylon formation over a larger surface area. Varying the amounts of HMD and sebacyl chloride (SC) used also affected the total weight of nylon formed. In general, more nylon is recovered as the level of each reactant increases. However, the molar ratio of HMD:SC determined the total amount of nylon formed when SC was present in excess.

Alginates↗