These data clearly demonstrate production of cytokines by T cells in RA synovial tissue, indicating that activated T cells play a role in the pathophysiological events of RA.

In this review the involvement of T cells, in addition to that of the monocyte/macrophage lineage, in the pathogenesis of rheumatoid arthritis is discussed. The evidence for the pathogenetic importance of T cells is based upon their state of activation in the synovial membrane and the cytokines produced. These cytokines can be detected in synovial fluids as well as in the synovial membrane by both immunohistochemistry and in situ hybridization. However, cytokine production can be detected only in a minor fraction of the T cells which contrasts the number of non-T cells observed to synthesize cytokines. Nevertheless, it can be assumed that the small amount of lymphokines is sufficient to activate a cytokine cascade derived from other cells. The cytokine profile secreted is indicative for a T cell response that primarily involves Th1-like cells.

In order to elucidate the role of the inflammatory cytokines in regulating glucocorticosteroid binding (GCSB) and glucocorticosteroid receptor (GR) level we incubated a B-cell line (CESS), a promonocytic cell line (U937) and a hepatoma cell line (HepG2) in the presence of varying concentrations of IL-1 beta, IL-6 and TNF-alpha for 24 h. Glucocorticosteroid binding was determined by the method of 'whole cell uptake', and the cellular appearance of the glucocorticosteroid receptor was detected by immunocytochemistry. A rise in the glucocorticosteroid binding was induced by all three cytokines. The increase in level of glucocorticosteroid receptors in the cells shown by immunocytochemistry was much more pronounced. However, antagonistic effects were demonstrated by both methods between IL-6 and TNF-alpha, and between IL-1 beta and TNF-alpha when they were applied simultaneously, in U937. Present data suggest that local imbalance in the ratio of these three cytokines in different pathological cases might influence the glucocorticosteroid sensitivity of the lymphocytes, monocytes and hepatocytes as target cells.

Insulin resistance (IR) and cardiometabolic disorders are the main consequences of today's alimentary behavior. This study evaluates the effects of a chronic-discontinuous treatment with alpha-lipoic acid (AL), an antioxidant substance that improves glycemic control associated with diabetes mellitus, on metabolic disorders and plasma oxidative stress induced by fructose intake, in rats. Sprague-Dawley rats (48 animals) were randomized into two series (n = 24): rats fed with standard chow or with standard chow supplemented with 60% fructose. In each of the two series, for 2 weeks/month over 12 weeks, a group of rats (n = 12) was intraperitoneally injected with NaCl 0.9%, and a second group (n = 12) received AL 50 mg/kg/day. Body weight, glycemia, and systolic blood pressure were monitored throughout the study. After 12 weeks, IR, plasma lipoproteins, uric acid, transaminase activities, and oxidative stress markers were assessed. The high fructose-enriched diet induced cardiometabolic disorders (hypertension, hyperglycemia, IR and dyslipidemia), an increase in uric acid concentration, transaminase activities and C-reactive protein level. This diet also enhanced plasma products of lipid and protein oxidation, homocysteine level, and decreased GSH/GSSG ratio. In this field, there is evidence to indicate that oxidative stress plays an important role in the etiology of diabetic complications. AL discontinuous treatment prevents the metabolic disorders induced by fructose intake, reduced plasma lipid and protein oxidation-products, and restored the GHS/GSSG ratio. Our study proves a promising potential of the chronic-discontinuous treatment of AL and highlights the pleiotropic effects of this antioxidant substance in metabolic disorders such as diabetes.

Taxus baccata L., an evergreen tree, was known until recently due to its high concentration of toxic compounds. The purpose of the present study was to focus on the only non-poisonous part, the red arils, which have recently been described as an important source of various bioactive constituents. To establish total phenolic, flavonoid, and carotenoid content, antioxidant capacity, and cytotoxic properties, two types of extracts were obtained. The chemical profile of the ethanolic extract was evaluated using chromatographic (HPLC-DAD-ESI+) and spectral (UV-Vis) methods, and the antioxidant activity of the ethanolic extract was assessed using DPPH and FRAP assays, yielding moderate results. In the second type of extract (methanol: ethyl acetate: petroleum ether (1:1:1, v/v/v)) we identified three carotenoids using open column chromatography and RP–PAD–HPLC, with rhodoxanthin being the most abundant. Considering the above and mainly because of the lack of information in the literature about this pigment and its biological effects, we decided to further investigate the cytotoxic activity of rhodoxanthin, the main carotenoid presented in aril, and its protective effect against H2O2-induced oxidative stress using two cell lines: human HaCaT keratinocytes and B16F10 murine malignant melanoma. The MTT and Annexin-V Apoptosis assays showed a substantial cytotoxic potential expressed in a dose-dependent manner towards the melanoma cell line, however, no obvious cytotoxic effects on human keratinocytes were noticed.