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      22-Oxacalcitriol Upregulates p21 WAF1/Cip1 in Human Parathyroid Glands

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          Abstract

          In the era of 22-oxacalcitriol (OCT), newly synthesized 1α,25-dihydroxyvitamin D<sub>3</sub> analogue, against secondary hyperparathyroidism, the indications of parathyroidectomy (PTx) has been restricted. Recent investigations on animal models have revealed the inhibitory effects on PTH secretion after OCT treatment, whereas there has been no evidence about human parathyroid glands. A 38-year-old man with a 19-year history of hemodialysis was performed PTx after the failure of OCT treatment. Expressions of proliferative nuclear cell antigen (PCNA), calcium-sensing receptor (CaSR), vitamin D receptor (VDR), p53 and p21<sup> WAF1/Cip1</sup> were analyzed by Western blotting and immunohistochemistry on resected parathroid glands. We confirmed up-regulations of CaSR and VDR, which contribute the reduction of serum PTH, by OCT treatment. Concomitant up-regulation of p21<sup> WAF1/Cip1</sup> but not p53, especially in nodular hyperplasia, can be considered to induce cell cycle arrest of the parathyroid cells, but not cytocidal effect of OCT.

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          Calcitriol per os Once, Twice or Three Times a Week: Effect of Different Schedules of Administration in Hemodialysis Patients

          Administration of a single dose of 1,25-OH 2 D 3 can lower PTH levels for up to 4 days in chronic hemodialysis patients. Our purpose was to verify the effects of the same weekly dose of calcitriol per os given in one, two or three administrations, to patients on dialysis with secondary hyperparathyroidism. Thirty patients were studied, divided in to three groups each of 10 patients. Calcitriol therapy in group A was given as a single weekly dose of 0.08 µg/kg b.w. In group B the same total weekly dose was divided in two equal doses. In group C the same total weekly dose was divided in three times. Treatment lastet 2 months. After 8 weeks of therapy the fall in intact PTH was statistically significant in each group, respectively with one-way ANOVA: p < 0.02 (A); p < 0.002 (B); p < 0.001 (c). Two-way ANOVA for comparison of PTH % variation among the three groups was statistically significant p < 0.003. Significance was due to difference between group A and groups B and C. The present study confirms the efficacy of single dose in suppressing significantly intact PTH. However, when the same weekly dose is divided into two or in three time-spaced administrations, the suppressive effects are definitely increased.
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            Author and article information

            Journal
            AJN
            Am J Nephrol
            10.1159/issn.0250-8095
            American Journal of Nephrology
            S. Karger AG
            0250-8095
            1421-9670
            2001
            December 2001
            28 December 2001
            : 21
            : 6
            : 507-511
            Affiliations
            aDepartment of Urology, Yamaguchi University School of Medicine, and bDepartment of Urology, Konan St. Hill Hospital, Ube, Yamaguchi, Japan
            Article
            46658 Am J Nephrol 2001;21:507–511
            10.1159/000046658
            11799271
            © 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: 2, References: 24, Pages: 5
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/46658
            Categories
            Laboratory Investigation

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