Antioxidant and antimutagenic activities of Viscum album fruit ethanolic extract in human lymphocytes

Polyphenolic compounds are widely distributed in plants and known to be excellent antioxidants in vitro. They have the capacity to reduce free-radical formation by scavenging free-radicals. In this studywe have evaluated the antioxidant and antimutagenic potencies of polyphenolic compounds of Viscum album against trichloroethylene (TCE)-induced oxidative and genotoxic damage. V. album extract (VAE0.5 g/ml) protected human lymphocytes against TCE. In chromosomal aberration (CA) analysis, no significant increase in total aberrations were found after treatment with TCE and all VAE concentrations. The mitotic index (MI) showed significant increase in 0.5 ìg/ml VAE samples whencompared with TCE-treated (2 ìM) group. VAE (0.5 ìg/ml) reduced the levels of malondialdehyde (MDA) significantly wherease VAE (1.0 and 2.0 ìg/ml) samples increased MDA concentrations significantly. We have also shown that the various DNA effects of TCE treatment seem to be DNA damages, but not mutations as TCE treated profiles were reverted back to the control like profiles by most probably DNA repair mechanisms in VAE 0.5 g/ml treated group

Genital ulcer severity score and genital health quality of life in Behçet's disease

Background: Behçet's Disease (BD) is a chronic auto-inflammatory, multisystem relapsing/remitting disorder of unknown aetiology. Oro-genital ulceration is a key feature of the disease and has a major impact on the patients' quality of life. Other clinical manifestations include ocular inflammation, rheumatologic and skin involvement, while CNS and vascular complications can lead to considerable morbidity. The availability of a valid monitoring tool for BD activity is crucial in evaluating the impact of the disease on daily life activity. The aims of this study were to validate a novel tool for monitoring genital ulceration severity in BD and to assess the impact of genital ulcers on the Genital Health Quality of Life (GHQoL). Methods: Genital Ulcer Severity Score (GUSS) was developed using six genital ulcer characteristics: number, size, duration, ulcer-free period, pain and site. A total of 207 BD patients were examined, (137 females: mean age∈±∈SD: 39.83∈±∈13.42 and 70 males: mean age∈±∈SD: 39.98∈±∈11.95) from the multidisciplinary Behçet's Centre of Excellence at Barts Health NHS Trust. GUSS was used in conjunction with Behçet's Disease Current Activity Form (BDCAF). Results: The over-all score of GUSS showed a strong correlation with all genital ulcer characteristics, and the strongest correlation was with the pain domain (r∈=∈0.936; P∈2: 0.600; P∈<∈0.0001). Conclusions: This study established the practicality of GUSS as a severity monitoring tool for BD genital ulcers and validated its use in 207 patients. Genital ulcers of BD have a considerable impact on the patients GHQoL

Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy

<p>Abstract</p> <p>Background</p> <p>The Toll-like receptors (TLRs) mediate innate immunity to various pathogens. A mutation (S180L) in the TLR downstream signal transducer <it>TIRAP </it>has recently been reported to be common in Europeans and Africans and to roughly half the risks of heterogeneous infectious diseases including malaria, tuberculosis, bacteremia, and invasive pneumococal disease in heterozygous mutation carriers.</p> <p>Methods</p> <p>We assessed the <it>TIRAP </it>S180L variant by melting curve and RFLP analysis in 1095 delivering women from malaria-endemic Ghana, as well as in a further 1114 individuals participating in case control studies on sepsis and leprosy in Germany, Turkey and Bangladesh.</p> <p>Results</p> <p>In Ghana, the <it>TIRAP </it>S180L polymorphism was virtually absent. In contrast, the mutation was observed among 26.6%, 32.9% and 12% of German, Bangladesh and Turkish controls, respectively. No significant association of the heterozygous genotype with sepsis or leprosy was observed. Remarkably, homozygous <it>TIRAP </it>180L tend to increase the risk of sepsis in the German study (<it>P </it>= 0.04).</p> <p>Conclusion</p> <p>A broad protective effect of <it>TIRAP </it>S180L against infectious diseases <it>per se </it>is not discernible.</p

Thrombosis in vasculitis: from pathogenesis to treatment

In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet’s syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet’syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet’s syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

Immunopathologic features of pemphigus in the east mediterranean region of Turkey: A prospective study

PubMedID: 20839419Pemphigus, a life-threatening autoimmune disorder, is the most common autoimmune bullous disease in the Mediterranean region of Turkey. No studies have investigated the immunopathologic features of this geographic setting. To determine the immunopathologic features of pemphigus in the Eastern Mediterranean region of Turkey, the authors evaluated the histopathological, immunofluorescence (IF), and enzyme-linked immunosorbent assay (ELISA) results in a 4-year study. In this prospective study, tissue from 174 patients was analyzed by direct IF (DIF); 384 by indirect IF (IIF) from 61 patients with pemphigus; and 88 by ELISA for antibodies against desmoglein (Dsg) 1 and Dsg 3 from 50 of those 61 patients. Pemphigus vulgaris (PV) was the most commonly observed subtype (46 of 61 patients, 75.41%), followed by pemphigus foliaceus (9 of 61 patients, 14.75%), pemphigus erythematosus (5 of 61 patients, 8.2%), and pemphigus herpetiformis (1 of 61 patients, 1.64%). There was a significant correlation between clinical activity score (CAS) and IgG antibody titer in IF (P<.001) and ELISA tests (P=.024 for Dsg 1; P=.028 for Dsg 3). Antibody titers and C3 scale did not predict exacerbations and relapse. The commonest clinical subtype of pemphigus was PV in this region. Results indicate that IgG antibody titer in IF and ELISA tests of patients with pemphigus are correlated with CAS; however, they are not useful in predicting exacerbations and relapse of disease. © 2010 Pulse Marketing & Communications, LLC. All rights reserved