Liver and intestinal protective effects of Castanea sativa Mill. bark extract in high-fat diet rats

The effects of Castanea sativa Mill. have been studied in high fat diet (HFD) overweight rats. Natural Extract of Chestnut bark (Castanea sativa Mill.) (ENC®), rich in ellagitannins, has been studied in 120 male Sprague-Dawley rats, divided in four groups. Two groups were controls: regular (RD) and HDF diet. Two groups received ENC®(20 mg/kg/day): RD + ENC®and HFD + ENC®. At baseline and at 7, 14 and 21 days, weight gain, serum lipids, plasma cytokines, liver histology, microsomial enzymes and oxidation, intestinal oxidative stress and contractility were studied. HFD increased body weight, increased pro-inflammatory cytokines, induced hepatocytes microvescicular steatosis, altered microsomial, increased liver and intestinal oxidative stress, deranged intestinal contractility. In HFD-fed rats, ENC®exerted antiadipose and antioxidative activities and normalized intestinal contractility, suggesting a potential approach to overweight management associated diseases

Biological agents therapy in crohn's disease

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with significant morbidity and health care costs. The disease seems to occur when the intestinal immune cascade is triggered by microbial antigens in genetically susceptible individuals. Over-activation of the enteric immune and inflammatory pathways causes mucosal damage resulting in the clinical signs and symptoms. Various medications, including 5-aminosalicylates, antibiotics, corticosteroids, and immune-modulators have traditionally been used to control inflammation. Their use is intended to prevent surgery and improve the patient's quality of life, but none cure the disease. Unfortunately, many patients require steroids to control their symptoms and a wide range of dose-related adverse effects makes this an unappealing strategy. Immune-modulators are effective maintenance drugs, but have a slow onset of action with clinical remission rates of approximately 40%. Recently, biological therapy has brought a paradigm shift in the management of CD and other autoimmune diseases, such as rheumatoid arthritis, psoriatic arthritis and multiple sclerosis (MS), resulting in marked decrease of disability and improvement in quality of life. Biologic therapies encompass agents with diverse modes of action, including the tumor necrosis factor a (TNFa) inhibitors, such as infliximab and adalimumab, that are the monoclonal antibody-based therapy of choice in CD. Natalizumab, an adhesion molecule inhibitor, is also used in refractory CD. Although the remarkable efficacy of biological therapy has resulted in significant success in CD management, serious side effects do occur, necessitating careful monitoring of therapy. In addition to other well documented neurologic, hematologic, immunologic, cardiovascular and malignant adverse effects, biological agents therapy has been associated with the development of serious life-threatening infections. In particular, the human polyomavirus JC (JCV) reactivation in CD after biological therapy and its association with progressive multifocal leukoencephalopathy (PML) has been found in one patient treated with natalizumab. After this case of PML and other two cases in MS patients, commercial and investigational use of natalizumab was suspended in February 2005 but was subsequently resumed for MS and for CD, only through a special restricted distribution program to patients who had refractory disease and who have failed both immune-suppressants and anti-TNFa agents and who have careful screening and subsequent monitoring for JCV infection. Therefore, this chapter will address an immunological overview of CD physiopathology, followed by the focusing on the use of infliximab, adalimumab and natalizumab in CD, and on their side effects, with particular attention to the issue of JCV reactivation. © 2013 Nova Science Publishers, Inc. All rights reserved

Reactivation of human polyomavirus JC in patients affected by psoriasis vulgaris and psoriatic arthritis and treated with biological drugs: Preliminary results

Psoriasis vulgaris (PsV) and psoriatic arthritis (PSA) are inter-related heritable inflammatory skin diseases. Psoriatic lesions develop as a result of abnormal immune responses, hyperproliferation and altered differentiation of keratinocytes, and a notable subset of psoriatic patients develops PsA, characterized by joints inflammation. Recently, biological drugs were introduced to treat these diseases. However, this therapy has already been associated with the development of serious life-threatening infections, such as the reactivation of human polyomavirus JC (JCV), responsible for the progressive multifocal leukoencephalopathy (PML), a lethal demyelinating disease caused by oligodendrocytes lytic infection. Therefore, the aims of our study were the investigation of the possible JCV reactivation in PsV and PsA patients treated with adalimumab, etanercept, and methotrexate, performing quantitative real-time PCR in sera and skin biopsies at the time of recruitment (T0) and after 3 (T3) and 6 (T6) months of treatment, and the sequencing analysis of the JCV non-coding control region (NCCR). We found JCV DNA in 5/15 PsV patients and in 2/15 PsA patients and JCV NCCR sequence analysis always showed a structure similar to non-pathogenic CY archetype, with random occurrence of a few irrelevant point mutations. Nevertheless the poor number of patients analyzed, our preliminary data can pave the way for taking into account that the follow-up of JCV DNA detection and the JCV NCCR sequence analysis in psoriatic patients may be important to evaluate the risk of PML onset, considering that patients affected by autoimmune diseases and treated with biologics continue to rise. J. Cell. Physiol. 227: 37963802, 2012. (c) 2012 Wiley Periodicals, Inc

Human polyomavirus JC reactivation and pathogenetic mechanisms of progressive multifocal leukoencephalopathy and cancer in the era of monoclonal antibody therapies

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the neurotropic human polyomavirus JC (JCV) lytic infection of oligodendrocytes. PML was first described as a complication of lymphoproliferative disorders more than 50 years ago and emerged as a major complication of human immunodeficiency virus (HIV) infection in the 1980s. Despite the ubiquity of this virus, PML is rare and always seen in association with underlying immunosuppressive condition, such as HIV infection, autoimmune diseases, cancer, and organ transplantation. JCV remains quiescent in the kidneys, where it displays a stable archetypal non-coding control region (NCCR). Conversely, rearranged JCV NCCR, including tandem repeat patterns found in the brain of PML patients, have been associated with neurovirulence. The specific site and mechanism of JCV NCCR transformation is unknown. According to one model, during the course of immunosuppression, JCV departs from its latent state and after entering the brain, productively infects and destroys oligodendrocytes. Although the majority of PML cases occur in severely immunesuppressed individuals, PML has been increasingly diagnosed in patients treated with biological therapies such as monoclonal antibodies (mAbs) that modulate immune system functions: in fact, CD4(+) and CD8(+) T lymphopenia, resulting from this immunomodulatory therapy, are the primary risk factor. Furthermore, JCV reactivation in nonpermissive cells after treatment with mAbs, such as intestinal epithelial cells in Crohn's disease patients, in association with other host tumor-inducing factors, could provide valid information on the role of JCV in several malignancies, such as colorectal cancer