The importance of the diet in relation to human health has increased the interest of consumers on nutraceuticals rich foods, and especially on fruits and vegetables. Berries are rich sources of a wide variety of antioxidant phenolics; these phytochemicals include flavonoids, stilbenes, tannins, and phenolic acids. Reactive oxidant species and free radicals are produced in an extensive range of physiological processes. In addition to the antioxidant defenses produced in the body, there are exogenous sources supplied by the diet; this is the case of berry fruits, among others. The insufficiency of antioxidant defense mechanisms is associated to the pathology of chronic disorders such as cardiovascular diseases, inflammation, and diabetes. Therefore, the enforcement of the latter mechanisms is of the utmost importance. The isolation and characterization of compounds that may delay the onset of aging is receiving intense research attention; some berry phenolics are being associated with this functional performance. Berry phenolics may also act as antimicrobials which may be of help in the control of the wild spectra of pathogens, in view of recent problems associated with antibiotic resistance. Most of the research works on the antioxidant activity of bioactive constituents of berries has been carried out using in vitro assays. In view of this, the human studies investigating the bioavailability and potential toxicity of phenolics are receiving more attention. Finally, we would like to emphasize the necessity of associating new plant breeding and genetic studies of berries with the expression and overexpression of compounds for human health and healthy aging.

SummaryThe aim of this study was to assess the effect of Adalimumab on different immune parameters in patients with RA. Adalimumab was administered (40 mg every other week for 26 weeks) to eight patients with RA that were refractory to conventional drug therapy. Peripheral blood samples were obtained at days 0, 15 and 180 of Adalimumab therapy, and the following immune parameters were assessed: Number, phenotype, and function of regulatory T lymphocytes. The induction of apoptosis of immune cells and the in vitro and in vivo reactivity towards M. tuberculosis were also analysed. All patients responded to Adalimumab (ACR response 50-70), and a modest but significant increase in the number and function of regulatory T cells was observed at day 15 of anti-TNF-a a a a therapy. In addition, an increased percent of apoptotic cells was detected in the peripheral blood at day 15 of Adalimumab therapy. Unexpectedly, most of these effects were not further observed at day 180. However, two patients showed a persistent and marked reduction in the reactivity to M. tuberculosis . Although we have found that Adalimumab affects the number and function of regulatory T lymphocytes, and the apoptosis of immune cells, these effects are transient and its possible causal relationship with the therapeutic activity of this biological agent remains to be determined. Nevertheless, the down-regulatory effect of Adalimumab on the reactivity to M. tuberculosis could be related to an enhanced risk of tuberculosis reactivation.

We studied the clinical and immunological effects of Rituximab (anti-CD20) therapy in patients with lupus nephritis. In an open clinical trial, 22 patients with active systemic lupus erythematosis and renal involvement (mainly class III and IV according to the WHO classification) that was refractory to conventional therapy were studied. In all these patients, Rituximab (0.5 to 1.0 g at days 1 and 15) was added to the immunosuppressive therapy and its therapeutic effect was evaluated. In addition, the levels and function of regulatory T lymphocytes and the apoptosis of immune cells were assessed. We found a significant reduction in disease activity (p < 0.05, MEX-SLEDAI index), and proteinuria (p < 0.05) at days 60 and 90 of Rituximab therapy. Although most patients showed improvement in creatinine clearance and erythrocyturia, no significant changes in these parameters were detected. In most patients (20/22), B cell depletion was observed, but no clearcut effect of Rituximab on complement levels or auto-antibody titers was detected (p > 0.05 in all cases). One patient died at day 70 with invasive histoplasmosis. No important adverse effects of Rituximab therapy were registered in other patients. A significant enhancement in the levels of different CD4+ regulatory cells (T REG , Th3, Tr1), but not CD8+ Ts lymphocytes, was observed at day 30. This increase was sustained for T REG cells at day 90, and accompanied by an improvement in their regulatory function. In addition, we observed an unexpected increase in the apoptosis of T cells at day 30. Interestingly, the enhancement in the suppressive function of T REG cells was not observed in the two patients that showed the poorest clinical response to Rituximab. We conclude that the data obtained in this open clinical trial suggest that Rituximab is a promising candidate for randomized controlled trials in patients with lupus nephritis refractory to the conventional immunosuppressive therapy. The effects of Rituximab on regulatory cells and apoptosis of T lymphocytes are interesting and its possible role in the putative effect of this biological agent in systemic lupus erythematosis deserves additional studies.

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The 3FDC test and reference formulations were not bioequivalent because the 90%CI for the geometric mean ratios did not meet the regulatory requirements for bioequivalence (range 80-125%) based on the rate and extent of absorption.