Biomedical subjects

C Whitworth

Publications and source records attributed to C Whitworth.

40 records · Page 3Linked to original sources

PubMed1984

Cochlear effects of locally applied inhibitors.

The round window has been used as a route for introducing ototoxic substances into the inner ear in order to bypass barriers between the systemic circulation and the inner ear. We have used this method to administer locally sodium potassium-ATPase inhibitors and chloride transport inhibitors to the inner ear of the chinchilla. Drugs dissolved in saline solution were applied on the round window membrane. Endocochlear potential (EP) was recorded from the basal turn using the round window approach. The EP was not altered following application of saline solution as a control. Following application of ouabain (1 mM), the EP steadily declined. After vanadate (27 mM), the EP initially increased, and subsequently declined. Sanguiarine did not alter the EP. The loop diuretics furosemide and piretanide caused a marked decline in the EP after local application. However, the stilbene derivative DIDS did not alter the EP after topical application. These findings raise questions about whether the loop diuretics have any effect on chloride transport in the cochlea and make appear unlikely that active chloride transport contributes to the normal EP.

Administration, Topical↗

PubMed1976

Multiple active forms of thrombin: binding to platelets and effects on platelet function.

The effect of various forms of thrombin on certain platelet functions has been investigated. Partially purified bovine thrombin which is a mixture of multiple active forms of thrombin, was chromatographed to yield molecular species termed alpha-, beta-, and gamma-thrombin, each of which has varying degrees of fibrinogen clotting and esterase activities. A direct correlation was observed between the ability of the different forms of thrombin to clot fibrinogen and to influence platelet function. In general, thrombin with high fibrinogen clotting activity was also a potent inducer of platelet aggregation and the release reaction, while those species with low clotting ability were poor inducers of aggregation and release.

Binding Sites↗

PubMedDate not supplied

Quinine reduces noxious cochlear effects of furosemide and ethacrynic acid.

Endocochlear potential (EP) and eighth nerve action potential (AP) were measured in chinchillas. We investigated the interaction of quinine with the loop diuretics furosemide and ethacrynic acid to determine whether the cochlear effects of these agents are attenuated by pretreatment with quinine. Animals were injected with either furosemide, 25 mg/kg intravenously (IV), or ethacrynic acid, 15 mg/kg IV. Control animals injected without pretreatment were found to have a large decrease in EP, with a decrease of compound action potentials (CAP) amplitude and an elevation of CAP threshold. Animals pretreated with quinine, 25 mg/kg, were found to have a significantly smaller reduction of EP and CAP amplitude following injection of either diuretic. No significant differences in urine volumes were noted between experimental and control groups. Quinine is known to cause nonspecific changes in the membranes of epithelial cells, which may cause alterations of the transport of organic anions by such tissues. Such an effect on epithelial cells in the cochlea may cause reduced uptake of loop diuretics in this organ, resulting in reduced toxicity.

Action Potentials↗

PubMedDate not supplied

Comparative ototoxicity of furosemide and piretanide.

The purpose of these studies was to compare the ototoxicity of piretanide to that of furosemide in the chinchilla. Chinchillas weighing 400 to 700 g were anesthetized with ketamine plus pentobarbital. Endocochlear potential (EP) was measured continuously by the round window approach using glass microelectrodes. Piretanide or furosemide injected through a jugular vein catheter in adults range from 10-100 mg/kg. Little or no change in EP was noted with doses below 15 mg/kg of either diuretic. The overall pattern of decline of EP was rather similar in piretanide-treated and furosemide-injected animals, and it was interesting to find that the dose-ototoxicity response curve for piretanide was similar to that for furosemide. The diuretic effect of equal ototoxic doses of either diuretic was equivalent. Both diuretics cause a decrease of endocochlear potential when applied locally to the round window membrane of the chinchilla as well as by systemic administration. These findings suggest that piretanide and furosemide have approximately the same propensity for ototoxicity.

Administration, Topical↗