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      Troglitazone Stimulates Basolateral Rheogenic Na +/HCO 3 Cotransport Activity in Rabbit Proximal Straight Tubules

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          Abstract

          Thiazolidinedione derivatives, new insulin-sensitizing antidiabetic agents, are expected to have potential clinical use. Since these drugs cause edema in a variable proportion of patients, we examined whether troglitazone (Tro) has direct action on Na<sup>+</sup> transport of rabbit proximal straight tubule perfused in vitro. For this purpose, we measured basolateral membrane voltage (V<sub>B</sub>) by conventional microelectrode techniques and intracellular pH (pH<sub>i</sub>) by microscopic fluorescence spectrophotometry with a pH-sensitive fluorescent dye, 2’, 7’-bis-2-carboxyethyl-5-carboxyfluorescein. Tro at 50 µ M in the bath significantly depolarized both transepithelial voltage and V<sub>B</sub>. To examine whether the basolateral rheogenic Na<sup>+</sup>/HCO<sup>–</sup><sub>3</sub> cotransport activity is affected by Tro, we observed V<sub>B</sub> deflection upon abrupt 10-fold decrease in bath HCO<sup>–</sup><sub>3</sub> in the absence and presence of Tro. The apparent transference number of HCO<sup>–</sup><sub>3</sub> ( t<sub>HCO3</sub>), as calculated from the V<sub>B</sub> deflection, was significantly greater in the presence of Tro (50 µM) than that seen in its absence. Tro caused cell acidification and increased the intracellular acidification rates (dpH<sub>i</sub>/dt) upon abrupt 10-fold decreases in bath HCO<sup>–</sup><sub>3</sub> and Na<sup>+</sup> concentrations. The stimulatory effects of Tro on t<sub>HCO3</sub> and dpH<sub>i</sub>/dt were dose dependent between 5 and 50 µ M, but they were unaffected at 0.5 µ M. From these results, we conclude that Tro acts on the proximal straight tubule and stimulates the basolateral rheogenic Na<sup>+</sup>/HCO<sup>–</sup><sub>3</sub> cotransport activity. The stimulatory action of Tro may partly account for edema formation.

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          A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection. Pediatric AIDS Clinical Trials Group.

          Serious bacterial infections are common in children infected with the human immunodeficiency virus (HIV). Studies performed before zidovudine became standard therapy found that intravenous immune globulin decreases the number of serious bacterial infections in these children. We designed a multicenter study to evaluate the efficacy of intravenous immune globulin in children with advanced HIV infection who were receiving zidovudine. In a double-blind trial 255 children between 3 months and 12 years of age who had the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were randomly assigned to receive either intravenous immune globulin (400 mg per kilogram of body weight) (n = 129) or placebo (0.1 percent albumin) (n = 126) every 28 days. All children received 180 mg of zidovudine per square meter of body-surface area orally four times daily. Treatment assignment was stratified according to whether the patients had a history of one or more serious bacterial infections, had previously been treated with zidovudine, or were currently receiving prophylaxis with trimethoprim-sulfamethoxazole. The median length of follow-up was 30.6 months. The estimated two-year rates of serious bacterial infections with confirmed pathogens were 16.9 percent for the immune globulin group and 24.3 percent for the placebo group (relative risk, 0.60; 95 percent confidence interval, 0.35 to 1.04; P = 0.07). The treatment effect was seen primarily among the 174 children who were not receiving trimethoprim-sulfamethoxazole prophylaxis at entry; the estimated two-year rates of infection were 11.3 percent for the immune globulin group and 26.8 percent for the placebo group (relative risk, 0.45; 95 percent confidence interval, 0.22 to 0.91; P = 0.03). For the 81 children who were receiving trimethoprim-sulfamethoxazole prophylaxis initially, the rates were 27.7 percent in the immune globulin group and 17.7 percent in the placebo group (relative risk, 1.26; 95 percent confidence interval, 0.44 to 3.66; P = 0.67). The two-year survival was similar in the two groups: 79.2 percent among immune globulin recipients and 75.4 percent among placebo recipients (P = 0.41). In children with advanced HIV disease who are receiving zidovudine, intravenous immune globulin decreases the risk of serious bacterial infections. However, this benefit is apparent only in children who are not receiving trimethoprim-sulfamethoxazole as prophylaxis.
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            Author and article information

            Journal
            EXN
            Nephron Exp Nephrol
            10.1159/issn.1660-2129
            Cardiorenal Medicine
            S. Karger AG
            1660-2129
            2001
            June 2001
            23 April 2001
            : 9
            : 3
            : 191-197
            Affiliations
            Departments of aNephrology and bPharmacology, Jichi Medical School, Kawachi, Tochigi, Japan
            Article
            52611 Exp Nephrol 2001;9:191–197
            10.1159/000052611
            11340303
            © 2001 S. Karger AG, Basel

            Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

            Page count
            Figures: 8, References: 26, Pages: 7
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/52611
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