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      The Effects of Diabetes Mellitus on Ovarian Injury and Reserve: An Experimental Study

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          Abstract

          Objective: The study aims to investigate the effects of diabetes mellitus (DM) on ovarian injury and reserve in a rat model. Study Design: In this prospective experimental study, 16 female Sprague-Dawley albino rats (12 weeks, 220-240 g) were randomly divided into 2 groups. Group 1 included 8 normal healthy rats as controls. No drug was administered to the controls. Group 2 included the other 8 rats in which diabetes was induced by intraperitoneal injections of streptozotocin (STZ). After overt DM occurred (blood glucose >250 mg/dl), all the animals were euthanized and blood samples were collected by cardiac puncture for biochemical analysis. Bilateral oophorectomy was performed for histopathological examination. Immunoexpressions of nuclear factor-kappa B (NF-kB) and caspase-3 as well as anti-Müllerian hormone (AMH) levels were assessed. Values were analyzed by t test. Results: Immunoexpressions of NF-kB and caspase-3 were significantly higher in non-treated diabetic rats than in the control group (p = 0.011 and p = 0.010, respectively). In healthy control group, AMH levels (3.22 ± 0.58 ng/ml) were significantly higher than in the non-treated diabetic group (1.41 ± 0.25 ng/dl; p = 0.024). Conclusion: Hyperglycemia causes severe ovarian injury via NF-kB pathway and caspase-3 apoptotic pathway, leading to the decrease in ovarian reserve in STZ-induced diabetic rats.

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          Oxidative stress as a mediator of apoptosis.

          Many agents which induce apoptosis are either oxidants or stimulators of cellular oxidative metabolism. Conversely, many inhibitors of apoptosis have antioxidant activities or enhance cellular antioxidant defenses. Mammalian cells exist in a state of oxidative siege in which survival requires an appropriate balance of oxidants and antioxidants. Thomas Buttke and Paul Sandstrom suggest that eukaryotic cells may benefit from this perilous existence by invoking oxidative stress as a common mediator of apoptosis.
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            Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme

            The interleukin-1 beta (IL-1 beta) converting enzyme (ICE) processes the inactive IL-1 beta precursor to the proinflammatory cytokine. Adherent monocytes from mice harboring a disrupted ICE gene (ICE-/-) did not export IL-1 beta or interleukin-1 alpha (IL-1 alpha) after stimulation with lipopolysaccharide. Export of tumor necrosis factor-alpha and interleukin-6 (IL-6) from these cells was also diminished. Thymocytes from ICE-/- mice were sensitive to apoptosis induced by dexamethasone or ionizing radiation, but were resistant to apoptosis induced by Fas antibody. Despite this defect in apoptosis, ICE-/- mice proceed normally through development.
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              The nuclear signaling of NF-kappaB: current knowledge, new insights, and future perspectives.

              The nuclear factor-kappa B (NF-kappaB) transcription factor plays a critical role in diverse cellular processes associated with proliferation, cell death, development, as well as innate and adaptive immune responses. NF-kappaB is normally sequestered in the cytoplasm by a family of inhibitory proteins known as inhibitors of NF-kappaB (IkappaBs). The signal pathways leading to the liberation and nuclear accumulation of NF-kappaB, which can be activated by a wide variety of stimuli, have been extensively studied in the past two decades. After gaining access to the nucleus, NF-kappaB must be actively regulated to execute its fundamental function as a transcription factor. Recent studies have highlighted the importance of nuclear signaling in the regulation of NF-kappaB transcriptional activity. A non-Rel subunit of NF-kappaB, ribosomal protein S3 (RPS3), and numerous other nuclear regulators of NF-kappaB, including Akirin, Nurr1, SIRT6, and others, have recently been identified, unveiling novel and exciting layers of regulatory specificity for NF-kappaB in the nucleus. Further insights into the nuclear events that govern NF-kappaB function will deepen our understanding of the elegant control of its transcriptional activity and better inform the potential rational design of therapeutics for NF-kappaB-associated diseases.
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                Author and article information

                Journal
                GOI
                Gynecol Obstet Invest
                10.1159/issn.0378-7346
                Gynecologic and Obstetric Investigation
                Gynecol Obstet Invest
                S. Karger AG (Basel, Switzerland karger@ 123456karger.com http://www.karger.com )
                0378-7346
                1423-002X
                September 2016
                19 December 2015
                : 81
                : 5
                : 424-429
                Affiliations
                Departments of aObstetrics and Gynecology, bAnesthesiology and Reanimation, cPathology, dCardiovascular Surgery, and eBiochemistry, Erzincan University, School of Medicine, Erzincan, Turkey
                Article
                GOI2016081005424 Gynecol Obstet Invest 2016;81:424-429
                10.1159/000442287
                26682912
                e39dd238-b183-4e8a-b6ec-adca76066efd
                © 2015 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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center. 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.

                History
                : 19 August 2015
                : 05 November 2015
                Page count
                Figures: 2, Tables: 1, References: 37, Pages: 6
                Categories
                Original Article

                Medicine,General social science
                Diabetes mellitus,NF-kB,Caspase-3,Ovarian failure,Rat
                Medicine, General social science
                Diabetes mellitus, NF-kB, Caspase-3, Ovarian failure, Rat

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