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      Intracellular Events in the Initiation of Calcium Oxalate Stones

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          Abstract

          This review summarizes our current understanding of intracellular events in the initiation of kidney stone formation, focusing on results from studies using renal epithelial cells in vitro. Such studies have shown that oxalate – either in crystalline or in soluble form – triggers a spectrum of responses in renal cells that favor stone formation, including alterations in membrane surface properties that promote crystal attachment and alterations in cell viability that provide debris for crystal nucleation. Activation of cytosolic PLA2 appears to play an important role in oxalate actions, triggering a signaling cascade that generates several lipid mediators (arachidonic acid, AA; lysophosphatidylcholine, Lyso-PC; ceramide) that act on key intracellular targets (mitochondria, nucleus). The net effect is increased production of reactive oxygen molecules (that in turn affect other cellular processes), an increase in cell death and an induction of a number of genes in surviving cells, some of which may promote proliferation for replacement of damaged cells, or may promote secretion of urinary macromolecules that serve to modulate crystal formation. A scheme is provided that explains how such oxalate-induced alterations could initiate stone formation in vivo.

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          Most cited references 22

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          Regulation of ceramide production and apoptosis.

          Ceramide is a sphingosine-based lipid signaling molecule that regulates cellular differentiation, proliferation, and apoptosis. The emerging picture suggests that coupling of ceramide to specific signaling cascades is both stimulus and cell-type specific. Ceramide action is determined within the context of other stimuli and by the subcellular topology of its production. Here, we discuss the pathways of ceramide generation and the interaction of ceramide with caspases and other apoptotic signaling cascades.
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            Mitochondrial reactive oxygen species in cell death signaling

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              Epidemiology and medical management of stone disease.

               H Tiselius (2003)
              Recurrent stone formation in the urinary tract is a common and important problem that must be considered in daily urological practice. With a prevalence of> 10% and an expected recurrence rate of approximately 50%, stone disease has an important effect on the healthcare system. It is generally agreed that patients with uric acid/urate, cystine or infection stones always should be treated pharmacologically. For calcium stone formers the treatment should be chosen according to the severity of the disease. Recurrence in patients with calcium-stone disease can be prevented with general or specific dietary and drinking advice, and with pharmacological therapy. For idiopathic calcium stone formers the most convincing therapeutic effects have been reported with thiazide and alkaline citrate.
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                Author and article information

                Journal
                NEE
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                978-3-8055-7852-3
                978-3-318-06156-7
                1660-2129
                2004
                October 2004
                17 November 2004
                : 98
                : 2
                : e61-e64
                Affiliations
                Department of Physiology, University of Massachusetts Medical School, Worcester, Mass., USA
                Article
                80258 Nephron Exp Nephrol 2004;98:e61–e64
                10.1159/000080258
                15499209
                © 2004 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: 1, References: 25, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/80258
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