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      Cell Death Markers in Children with Immune Thrombocytopenic Purpura: A Preliminary Study

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          Abstract

          Immune thrombocytopenic purpura (ITP) is an autoimmune disease with possible dysregulation of the apoptotic pathways. We aimed to evaluate the possible role of some apoptotic markers (caspase 3, caspase 8 and BCL2) in the pathogenesis and course of ITP. We investigated some apoptotic markers (caspase 3, caspase 8 and BCL2) using the flow cytometry in 60 children with newly diagnosed ITP, 20 children with chemotherapy-related thrombocytopenia (CRT) and 20 healthy children. We also assessed the effects of intravenous immunoglobulin (IVIG) and methyl prednisolone therapies on the platelet apoptosis in children with newly diagnosed ITP. We demonstrated significantly higher values of caspase 3 in the newly diagnosed ITP group than control and CRT groups, and non-significantly higher values of caspase 8 in the ITP group than the healthy group. After IVIG treatment, the platelet count increased in all patients, and there was a significant decrease in caspase 3 and caspase 8 levels while BCL2 level increased. Regarding methylprednisolone treatment, there was a significant decrease in BCL2 and caspase 8 levels while caspase 3 levels did not significantly decrease. There is a possible role of the caspase dependent cell death pathway of the platelets in the occurrence of newly diagnosed ITP. There is heterogeneity in the apoptotic changes of newly diagnosed ITP children who received IVIG versus those who received methylprednisolone.

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          Most cited references27

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          The BCL-2 protein family: opposing activities that mediate cell death.

          BCL-2 family proteins, which have either pro- or anti-apoptotic activities, have been studied intensively for the past decade owing to their importance in the regulation of apoptosis, tumorigenesis and cellular responses to anti-cancer therapy. They control the point of no return for clonogenic cell survival and thereby affect tumorigenesis and host-pathogen interactions and regulate animal development. Recent structural, phylogenetic and biological analyses, however, suggest the need for some reconsideration of the accepted organizational principles of the family and how the family members interact with one another during programmed cell death. Although these insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, a unifying hypothesis for the mechanisms they use to activate caspases remains elusive.
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            Death and anti-death: tumour resistance to apoptosis.

            Every cell in a multicellular organism has the potential to die by apoptosis, but tumour cells often have faulty apoptotic pathways. These defects not only increase tumour mass, but also render the tumour resistant to therapy. So, what are the molecular mechanisms of tumour resistance to apoptosis and how can we use this knowledge to resensitize tumour cells to cancer therapy?
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              Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura.

              The pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP) involves antibody-mediated platelet destruction and reduced platelet production. Stimulation of platelet production may be an effective treatment for this disorder. We conducted a trial in which 118 adults with chronic ITP and platelet counts of less than 30,000 per cubic millimeter who had had relapses or whose platelet count was refractory to at least one standard treatment for ITP were randomly assigned to receive the oral thrombopoietin-receptor agonist eltrombopag (30, 50, or 75 mg daily) or placebo. The primary end point was a platelet count of 50,000 or more per cubic millimeter on day 43. In the eltrombopag groups receiving 30, 50, and 75 mg per day, the primary end point was achieved in 28%, 70%, and 81% of patients, respectively. In the placebo group, the end point was achieved in 11% of patients. The median platelet counts on day 43 for the groups receiving 30, 50, and 75 mg of eltrombopag were 26,000, 128,000, and 183,000 per cubic millimeter, respectively; for the placebo group the count was 16,000 per cubic millimeter. By day 15, more than 80% of patients receiving 50 or 75 mg of eltrombopag daily had an increased platelet count. Bleeding also decreased during treatment in these two groups. The incidence and severity of adverse events were similar in the placebo and eltrombopag groups. Eltrombopag increased platelet counts in a dose-dependent manner in patients with relapsed or refractory ITP. (ClinicalTrials.gov number, NCT00102739.) 2007 Massachusetts Medical Society
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                Author and article information

                Contributors
                wahbayahya2007@mans.edu.eg , yahyawahba@ymail.com
                Journal
                Indian J Hematol Blood Transfus
                Indian J Hematol Blood Transfus
                Indian Journal of Hematology & Blood Transfusion
                Springer India (New Delhi )
                0971-4502
                0974-0449
                25 February 2023
                25 February 2023
                October 2023
                : 39
                : 4
                : 635-641
                Affiliations
                [1 ]Pediatric Department, Mansoura University Faculty of Medicine, ( https://ror.org/01k8vtd75) Mansoura, Egypt
                [2 ]Department of Medical Microbiology and Immunology, Mansoura University Faculty of Medicine, ( https://ror.org/01k8vtd75) Mansoura, Egypt
                [3 ]Clinical Biochemistry, Mansoura University Children Hospital, Mansoura University Faculty of Medicine, ( https://ror.org/01k8vtd75) Mansoura, Egypt
                [4 ]Pediatric Department, Misr University for Science and Technology Faculty of Medicine, ( https://ror.org/05debfq75) Cairo, Egypt
                Author information
                http://orcid.org/0000-0001-7479-7866
                Article
                1639
                10.1007/s12288-023-01639-0
                10542074
                37786823
                32d9dc40-6c90-4534-b325-2fe01b163eae
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 August 2022
                : 15 February 2023
                Funding
                Funded by: Mansoura University
                Categories
                Original Article
                Custom metadata
                © Indian Society of Hematology and Blood Transfusion 2023

                bcl2,caspase 3,caspase 8,itp,ivig,methylprednisolone
                bcl2, caspase 3, caspase 8, itp, ivig, methylprednisolone

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