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      Apoptosis and Clinical Severity in Patients with Psoriasis and HCV Infection

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          Abstract

          Background:

          It has been proposed that hepatitis C virus (HCV) antigens are involved in the pathogenesis of psoriasis and may contribute to severity of the disease. Increased expression of the apoptosis-regulating proteins p53 and tTG and decreased levels of bcl-2 in the keratinocytes of the skin of psoriatic patients have been reported.

          Aim:

          This study aims to identify the serum levels of apoptosis-regulating proteins in patients with psoriasis and without HCV infection and to study the relation between clinical severity of psoriasis and the presence of HCV infection.

          Materials and Methods:

          Disease severity was assessed by psoriasis area severity index score (PASI) of 90 patients with psoriasis grouped as mild ( n = 30), moderate ( n = 30) and severe ( n = 30); 20 healthy individuals were used as controls. All groups were subjected for complete history taking, clinical examination, and tests for liver function and HCV infection. The serum levels of apoptosis related proteins: p53, tTG and bcl-2 were estimated by enzyme linked immune sorbent assay (ELISA).

          Results:

          There was a statistically significant ( P < 0.001) correlation between clinical severity of psoriasis and presence of HCV antibodies and HCV-mRNA. In addition, significantly ( P < 0.001) raised serum p53 and tTG, and reduced bcl-2 were observed among HCV-positive patients as compared to HCV-negative patients and control patients.

          Conclusion:

          These results conclude that clinical severity of psoriasis is affected by the presence of HCV antibodies and overexpression of apoptotic related proteins. In addition, altered serum levels of apoptosis-regulating proteins could be useful prognostic markers and therapeutic targets of psoriatic disease.

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          Most cited references41

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          Apoptosis in nonalcoholic fatty liver disease: diagnostic and therapeutic implications.

          Pathological increases in cell death in the liver as well as in peripheral tissues has emerged as an important mechanism involved in the development and progression of nonalcoholic fatty liver disease (NAFLD). An increase in hepatocyte cell death by apoptosis is typically present in patients with NAFLD and in experimental models of steatohepatitis, while an increase in adipocyte cell death in visceral adipose tissue may be an important mechanism triggering insulin resistance and hepatic steatosis. The two fundamental pathways of apoptosis, the extrinsic (death receptor-mediated) and intrinsic (organelle-initiated) pathways, are both involved. This article summarizes the current knowledge related to the distinct molecular and biochemical pathways of cell death involved in NAFLD pathogenesis. In particular, it will highlight the efforts for the development of both novel diagnostic and therapeutic strategies based on this knowledge.
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            Immunopathogenesis of psoriasis.

            Psoriasis is a chronic skin disease that affects about 1.5% of the Caucasian population and is characterized by typical macroscopic and microscopic skin alterations. Psoriatic lesions are sharply demarcated, red and slightly raised lesions with silver-whitish scales. The microscopic alterations of psoriatic plaques include an infiltration of immune cells in the dermis and epidermis, a dilatation and an increase in the number of blood vessels in the upper dermis, and a massively thickened epidermis with atypical keratinocyte differentiation. It is considered a fact that the immune system plays an important role in the pathogenesis of psoriasis. Since the early 1990s, it has been assumed that T1 cells play the dominant role in the initiation and maintenance of psoriasis. However, the profound success of anti-tumor necrosis factor-alpha therapy, when compared with T-cell depletion therapies, should provoke us to critically re-evaluate the current hypothesis for psoriasis pathogenesis. Recently made discoveries regarding other T-cell populations such as Th17 and regulatory T cells, dendritic cells, macrophages, the keratinocyte signal transduction and novel cytokines including interleukin (IL)-22, IL-23 and IL-20, let us postulate that the pathogenesis of psoriasis consists of distinct subsequent stages, in each of them different cell types playing a dominant role. Our model helps to explain the varied effectiveness of the currently tested immune modulating therapies and may enable the prediction of the success of future therapies.
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              Typing hepatitis C virus by polymerase chain reaction with type-specific primers: application to clinical surveys and tracing infectious sources.

              Based on variation in nucleotide sequence within restricted regions in the putative C (core) gene of hepatitis C virus (HCV), four groups of HCV have been postulated in a panel of 44 HCV isolates. They were provisionally designated types I, II, III and IV. A method for typing HCV was developed, depending on the amplification of a C gene sequence by polymerase chain reaction using a universal primer (sense) and a mixture of four type-specific primers (antisense). HCV types were determined by the size of the products specific to each of them. Type II was found in HCV samples from 131 (82%) of 159 blood donors, more often than in those from 48 (60%) of 80 patients with non-A, non-B (NANB) liver disease in Japan (P less than 0.01). In 11 haemophiliacs who had received imported coagulation factor concentrates, type I was found in five, as against type II in four. Double infection with two different HCV types was found in two patients with chronic NANB liver disease (types I and II; II and III) and two haemophiliacs (types I and II; I and III). HCV types were identical in mother and baby in each of two examples of perinatal transmission, and were also identical in donor and recipient in a case of accidental needle exposure.
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                Author and article information

                Journal
                Indian J Dermatol
                Indian J Dermatol
                IJD
                Indian Journal of Dermatology
                Medknow Publications & Media Pvt Ltd (India )
                0019-5154
                1998-3611
                May-Jun 2014
                : 59
                : 3
                : 230-236
                Affiliations
                [1 ] From the Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt
                [2 ] Rehabilitation Research Chair, College of Applied Medical Sciences, King Saud University, Riyad, Saudi Arabia
                [3 ] Rehabilitation Science Department, College of Applied Medical Sciences, King Saud University, Riyad, Saudi Arabia
                [4 ] Medical Experimental Research Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt
                Author notes
                Address for correspondence: Dr. Sami A. Gabr, Rehabilitation Research Chair, King Saud University, Riyadh, Saudi Arabia. E-mail: nadalab2009@ 123456hotmail.com
                Article
                IJD-59-230
                10.4103/0019-5154.131377
                4037940
                3f3070e4-7f82-49a7-980f-167a352baee8
                Copyright: © Indian Journal of Dermatology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : October 2012
                : July 2013
                Categories
                Investigative Dermatology

                Dermatology
                apoptosis,b cell lymphoma-2 protein,hepatitis c virus,p53,psoriasis,tissue transglutaminase

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