Lack of effects of isoflavones on the lipid profile of Brazilian postmenopausal women

Objective: To evaluate the effects of soy isoflavone supplementation on profile lipid and endogenous hormone levels. Methods: In this double-blind, placebo-controlled Study, 47 post menopausal women 47-66 v of age received 40 mg of isoflavone (n = 25) or 40 mg of casein placebo (11 = 22). Cardiovascular risk factors were assessed by evaluating lipid profile at baseline and after 6 mo of treatment. To examine the effects of this regime on endogenous hormone levels, follicle-stimulating hormone and beta-estradiol were measured. Urinary isoflavone concentrations (genistein and daidzein) were measured as markers of both compliance and absorption using high performance liquid chromatography. Baseline characteristics were compared by the unpaired Student`s t-test. Within-group changes were determined by paired Student`s t-test and comparison between the isoflavone and casein placebo groups were determined by analysis of variance. Results: Lipid levels (low-density lipoprotein and total cholesterol) similarly decreased in both,groups. High-density lipoprotein increased significantly in both groups and cannot thus be attributable to treatment: the reason for Such variation is unknown and can be attributed to chance or to bias (even that of a real placebo effect in both groups or perhaps in spontaneous changes in exercise and dietary habits of patients after their inclusion). Furthermore, in both groups very low-density lipoprotein and triacylglycerol levels increased in a non-significant manner. Conclusion: The results of the present Study do not support any biologically significant estrogenic effects of isoflavone on the parameters assessed. Further research will he necessary to definitively assess the safety and efficacy of isoflavone. (C) 2008 Elsevier Inc. All rights reserved.FAPESPFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CAPES/BRAZILCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Validation by RQ-PCR and flow cytometry of alpha-defensin1-3 (DEFA1-3) overexpression in relapsed and refractory acute lymphoblastic leukemia

In spite of high Cure rates and improved overall survival, 25% of pediatric patients with acute lyrnphoblastic leukemia (ALL) relapse after obtaining complete remission. Additionally a small proportion of patients are refractory and do not attain remission. Microarray expression analysis of matched diagnosis-relapse B-lineage ALL sample pairs identified DEFA1-3 as a potential marker of relapse. Here, Validation of DEFA1-3 as a marker for therapy resistance is explored. DEFA1-3 expression was analysed by RQ-PCR in patient paired samples at diagnosis and relapse of 6 earlyrelapse (within 18 months) and 8 late-relapse (beyond 18 months) B-lineage ALL. Diagnostic samples of 19 patients with ALL who are in continuous complete remission (median time from diagnosis 47 month) and diagnostic samples of 5 refractory patients who had not achieved remission at day 35 of therapy were also analyzed. In addition, overexpression of alpha-defensitil-3 proteins in blast cells at relapse was analysed by flow cytometry. DEFA1-3 was overexpressed at relapse as compared to diagnosis in 12 of 14 samples. At diagnosis, the expression of DEFA1-3 was significantly higher in samples from refractory patients as compared to those of patients who are in CR and to those of patients who experienced late relapse. At diagnosis, patients who relapsed early after diagnosis could not be distinguished from refractory patients based on DEFA1-3 expression levels. Results Suggest that high levels of DEFA1-3 mRNA and alpha-defensin1-3 protein expression are correlated with disease progression and failure of adequate response to conventional chemotherapy

Effects of isoflavones on the coagulation and fibrinolytic system of postmenopausal women

Objective: We evaluated the effects of soy isoflavone supplementation on hemostasis in healthy postmenopausal women. Methods: In this double-blinded, placebo-controlled study, 47 postmenopausal women 47-66 y of age received 40 mg of soy isoflavone (n = 25) or 40 mg of casein placebo (n = 22) once a day for 6 mo. Levels of factors VII and X. fibrinogen, thrombin-antithrombin complex, prothrombin fragments I plus 2, antithrombin, protein C, total and free protein S, plasminogen, plasminogen activator inhibitor-1, and D-dimers were measured at baseline and 6 mo. Urinary isoflavone concentrations (genistein and daidzein) were measured as a marker of compliance and absorption using high-performance liquid chromatography. Baseline characteristics were compared by unpaired Student`s t test. Within-group changes and comparison between the isoflavone and casein placebo groups were determined by a mixed effects model. Results: The levels of hemostatic variables did not change significantly throughout the study in the isoflavone group; however, the isoflavone group showed a statistically significant reduction in plasma concentration of prothrombin fragments I plus 2; both groups showed a statistically significant reduction in antithrombin, protein C, and free protein S levels. A significant increase in D-dimers was observed only in the isoflavone group. Plasminogen activator inhibitor-l levels increased significantly in the placebo group. However, these changes were not statistically different between groups. Conclusion: The results of the present study do not support a biologically significant estrogenic effect of soy isoflavone on coagulation and fibrinolysis in postmenopausal women. However, further research will be necessary to definitively assess the safety and efficacy of isoflavone. (D 2008 Elsevier Inc. All rights reserved

Current scientific understanding of urinary tract infections in women: An overview

Bacterial vaginosis (BV) is the most prevalent vaginal infection worldwide and is characterized by depletion of the indigenous lactobacilli. Antimicrobial therapy is often ineffective. We hypothesized that probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 might provide an adjunct to antimicrobial treatment and improve cure rates. Sixty-four Brazilian women diagnosed with BV were randomly assigned to receive a single dose of tinidazole (2 g) supplemented with either 2 placebo capsules or 2 capsules containing L. rhamnosus GR-1 and L. reuteri RC-14 every morning for the following 4 weeks. At the end of treatment (day 28), the probiotic group had a significantly higher cure rate of BV (87.5%) than the placebo group (50.0%) (p = 0.001). In addition, according to the Gram-stain Nugent score, more women were assessed with normal vaginal microbiota in the probiotic group (75.0% vs. 34.4% in the placebo group; p = 0.011). This study shows that probiotic lactobacilli can provide benefits to women being treated with antibiotics for an infectious condition

Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial

Bacterial vaginosis (BV) is the most prevalent vaginal infection worldwide and is characterized by depletion of the indigenous lactobacilli. Antimicrobial therapy is often ineffective. We hypothesized that probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 might provide an adjunct to antimicrobial treatment and improve cure rates. Sixty-four Brazilian women diagnosed with BV were randomly assigned to receive a single dose of tinidazole (2 g) supplemented with either 2 placebo capsules or 2 capsules containing L. rhamnosus GR-1 and L. reuteri RC-14 every morning for the following 4 weeks. At the end of treatment (day 28), the probiotic group had a significantly higher cure rate of BV (87.5%) than the placebo group (50.0%) (p = 0.001). In addition, according to the Gram-stain Nugent score, more women were assessed with ""normal`` vaginal microbiota in the probiotic group (75.0% vs. 34.4% in the placebo group; p = 0.011). This study shows that probiotic lactobacilli can provide benefits to women being treated with antibiotics for an infectious condition.FAPESP Sao Paulo State Foundation for Support of Science[04/14580-0]Brazilian Post Graduate Federal Agency[6159/06-2]FAPESP[06/06595-2]Natural Sciences and Engineering Research Council of Canada (NSERC

CTLA-4 in mesothelioma patients: tissue expression, body fluid levels and possible relevance as a prognostic factor.

CTLA-4 function as a negative regulator of T cell-mediated immune response is well established, whereas much less is known about the immunoregulatory role of its soluble isoform (sCTLA-4). No data are available on CTLA-4 expression and prognostic impact in malignant pleural mesothelioma (MPM). We investigated, by immunohistochemistry, CTLA-4 expression in tumor tissues and, by ELISA, sCTLA-4 levels in sera and matched pleural effusions from 45 MPM patients. Prognostic effect of CTLA-4 expression on overall survival (OS) was assessed through Cox regression and prognostic significance expressed as death rate ratio (HR). We found that 56.0 % of MPM tissues expressed CTLA-4 with variable intensity and percentage of positive cells estimated by the immunoreactive score. sCTLA-4 levels were significantly higher in sera (S-sCTLA-4) than in pleural effusions (PE-sCTLA-4) (geometric mean ratio = 2.70, P value = 0.020). CTLA-4 expression at the tissue level was higher in the epithelioid histological subtype than in the sarcomatoid, whereas at the serum level, it was higher in the sarcomatoid subtype. A homogeneous favorable prognostic effect was found for CTLA-4 overexpression in tissue, serum and pleural effusion. Interestingly, only the PE-sCTLA-4 was found to be a statistically significant positive prognostic factor (HR = 0.37, 95 % CI = 0.18\u20130.77, P value = 0.007). Indeed, PE-sCTLA-4 correlated with CTLA-4 expression in tissues, whereas this latter expression showed a weak association with OS. To confirm our findings, further experimental evidences obtained from a larger cohort of MPM patients are required. However, our results would indicate a positive correlation of PE-sCTLA-4 levels and OS in MPM patients