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Poitiers, France

The severity of hepatitis C virus (HCV) infection is related to the liver complications, i.e., cirrhosis and hepato-cellular carcinoma and also to extrahepatic manifestations (EHM). Some of these EHM are well characterized; for oethers, the association to HCV is discussed. The best known are associated with mixed cryoglobulinemia due to HCV lymphotropism. This systemic vasculitis induce mild EHM however associated with poor quality of life (purpura, arthralgia, fatigue) or severe EHM rarely affecting short term prognosis (renal, nervous sytem, B lymphoma). In presence of clinical signs of EHM, anti-HCV treatment with new direct antiviral agents is mandatory whatever the severity of liver fibrosis. In presence of lymphoproliferative B disorder, immunosuppressive drugs are justified. Some EHM not related to mixed cryoglobulinemia are induced by HCV chronic inflammation and liver disease worsened long term prognosis (cardiovascular diseases, diabetes) and required anti-HCV treatment in presence of moderate or severe liver fibrosis. The aim of this clinical case is to describe these EHM, to ensure their diagnosis and their treatment.

Tougeron D.,CHU de Poitiers | Tougeron D.,French Institute of Health and Medical Research | Tougeron D.,Laboratoire inflammation | Fauquembergue E.,French Institute of Health and Medical Research | Latouche J.-B.,French Institute of Health and Medical Research
Bulletin du Cancer | Year: 2013

Immune response has a crucial role in the control of tumoral progression in colorectal cancer (CRC). A close link between the rate of tumor infiltrating lymphocytes and prognosis has been found. Indeed, recent studies have shattered our dogmas as the rate of tumor infiltrating lymphocytes seems to be a better prognostic factor than TNM classification. This review is focused on immune response in CRC. Specific cell-mediated immunity is important for the control of tumoral growth. Specific T cell activation is induced by tumoral antigens process by dendritic cells. Among the numerous tumoral antigens that could induce an immune response in CRC, the carcinoembryonic antigen is the most studied but its immunogenicity remains low. In CRC with microsatellite instability, several immunogenic neo-antigens have been identified and could explain the high level of tumor infiltrating lymphocytes and the better prognosis of this type of tumour. However, CRC can escape immune response by immune response modulation or tumoral cells modifications conducting to immune resistance. These data should be considered for the treatment of CRC or the development of immunotherapy strategies. © John Libbey Eurotext.

Chaulet C.,CNRS Genetics, Immunotherapy, Chemistry & Cancer Laboratory | Croix C.,CNRS Genetics, Immunotherapy, Chemistry & Cancer Laboratory | Alagille D.,CNRS Genetics, Immunotherapy, Chemistry & Cancer Laboratory | Normand S.,Laboratoire inflammation | And 4 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2011

Several thalidomide analogues were synthesized and compared to thalidomide and its more active analogue, lenalidomide, for their ability to inhibit the production of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α and interleukin (IL)-6 by LPS-activated peripheral blood mononuclear cells (PBMCs). Among these compounds, two analogues containing sulfonyl group displayed interesting downregulation of TNF-α and IL-6 production. © 2010 Elsevier Ltd. All rights reserved.

Nader J.,University of Poitiers | Nader J.,French National Center for Scientific Research | Claudia C.,French National Center for Scientific Research | Claudia C.,University of Poitiers | And 10 more authors.
Neuropsychopharmacology | Year: 2012

Life experiences, especially during critical periods of maturation, such as adolescence, can dramatically affect vulnerability to diseases at adulthood. Early exposure to positive environmental conditions such as environmental enrichment (EE) has been shown to reduce the occurrence and the intensity of neurological and psychiatric disorders including drug addiction. However, whether or not exposure to EE during early stages of life would protect from addiction when, at adulthood, individuals may find themselves in non-enriched conditions has not been investigated. Here we show that switching mice from EE to non-enriched standard environments not only results in the loss of the preventive effects of EE but also increases the rewarding effects of cocaine. This enhanced vulnerability is associated with emotional distress and with increased levels in the mRNA levels of corticotropin releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST), as well as with increases in CREB phosphorylation in the BNST and in the shell of the nucleus accumbens. The increased sensitivity to the rewarding effects of cocaine is completely blocked by the CRF antagonist antalarmin, confirming a major role of the CRF system in the negative consequences of this environmental switch. These results indicate that positive life conditions during early stages of life, if they are not maintained at adulthood, may have negative emotional consequences and increase the risks to develop drug addiction. © 2012 American College of Neuropsychopharmacology.

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