Genistein at Maximal Physiologic Serum Levels Induces G0/G1 Arrest in MCF-7 and HB4a Cells, But Not Apoptosis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Inhibition of tooth erosion by milk containing different fluoride concentrations: An in vitro study

Objectives: This in vitro study assessed the effect of milk containing different fluoride concentrations on tooth erosion.Methods: Bovine enamel and root dentine specimens were treated with: (1) bovine whole milk with 0 ppmF; (2) 2.5 ppm F; (3) 5 ppmF;(4) 10 ppmF (all after erosion); (5) whole milk with 0 ppm F (before erosion); (6) NaF (0.05% F, positive control, after erosion) or (7) 0.9% NaCl (negative control, after erosion). The specimens were submitted to pH cycles (4 x 90 s in soft drink) and treatments for 5 days. The specimens were immersed in the treatment solutions for 1 min(only at the first cycle each day) with further exposition to 1: 1 milk: saliva slurry for 10 min. The tooth loss was measured using a contact profilometer and statistically analysed (p < 0.05).Results: Rinsing with milk before erosive challenge significantly reduced tooth loss compared to negative control (67% and 24% reduction in dentine and enamel loss, respectively) and to milk after erosive challenge, only for dentine. The addition of fluoride to milk also reduced tooth loss compared to negative control, but with no significant differences among fluoride concentrations for enamel and dentine (mu m), respectively: 0 ppm (3.63 +/- 0.04 and 2.51 +/- 0.53), 2.5 ppm F (2.86 +/- 0.42 and 1.96 +/- 0.47), 5 ppm F (2.81 +/- 0.27 and 1.77 +/- 0.44), 10 ppm F (2.03 +/- 0.49 and 1.68 +/- 0.59). There was a negative and significant correlation between [F] and the tooth loss.Conclusions: Daily rinse with milk containing F is able to reduce both enamel and dentine erosion in vitro.Clinical significance: Since the prevalence of dental erosion is steadily increasing, rinse with milk or its derivate might be an important strategy to reduce the progression of tooth erosion. (C) 2013 Elsevier Ltd. All rights reserved.

Potassium nutrition in the first and second ratoon sugarcane grown in an Oxisol by a conservationist system

The presence of mulch on the soil surface after the mechanical harvesting of sugarcane (Saccharum officinarum L.) enhances the cycling of nutrients, especially K, which can decrease K fertilizer recommendations for the crop. The aim of this study was to evaluate the effect of K addition to an Oxisol, with an initial concentration 0.07 cmol(c) K kg(-1), in first and second ratoon (no-till) sugarcane cultures by a conservationist system, i.e. rational use of fertilizers, use of alternative inputs and especially the maintenance of residues in soil that was previously burned to facilitate cutting. The following K doses were tested: 0, 32.5, 65, 130, and 195 kg K2O ha(-1), arranged in a randomized block design with five replicates. Potassium content in the soil and in the plant, as well as the yield and the quality of stalks were evaluated. Soil K application increased K concentration in soil and plant, and was reflected in the prodUction of stalks, with higher production (87.5 and 107.5 t ha(-1)) with the use of 120 and 123 kg K2O ha(-1) in first and second ratoon sugarcane, respectively. At the first 2 yr it was not possible to reduce the K fertilization in ratoon. Therefore, with the introduction of the conservationist system there was an increase (20 t ha(-1)) at the second ratoon regarding the first one with the same applied rate.

Does clinical treatment with phenylbutazone and meloxicam in the pre-ovulatory period influence the ovulation rate in mares?

The presence of anovulatory haemorrhagic follicles during the oestrous cycle of mares causes financial impacts, slowing conception and increasing the number of services per pregnancy. Non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and phenylbutazone are used in the treatment of several disorders in mares, and these drugs can impair the formation of prostaglandins (PGs) and consequently interfere with reproductive activity. This study aimed to evaluate the effects of treatment with NSAIDs on the development of pre-ovulatory follicles in mares. In total, 11 mares were studied over three consecutive oestrous cycles, and gynaecological and ultrasound examinations were performed every 12 h. When 32-mm-diameter follicles were detected, 1 mg of deslorelin was administered to induce ovulation. The first cycle was used as a control, and the mares received only a dose of deslorelin. In the subsequent cycles, in addition to receiving the same dose of deslorelin, each mare was treated with NSAIDs. In the second cycle, 4.4 mg/kg of phenylbutazone was administered, and in the third cycle, 0.6 mg/kg of meloxicam was administered once a day until ovulation or the beginning of follicular haemorrhage. All of the mares ovulated between 36 and 48 h after the induction in the control cycle. In the meloxicam cycle, 10 mares (92%) did not ovulate, while in the phenylbutazone cycle, nine mares (83%) did not ovulate. In both treatments, intrafollicular hyperechoic spots indicative of haemorrhagic follicles were observed on ultrasound. Thus, our results suggested that treatment with meloxicam and phenylbutazone at therapeutic doses induced intrafollicular haemorrhage and luteinization of anovulatory follicles.

Análise de pathway e network em tecido adiposo in vivo e o papel da vitamina D na adipogênese in vitro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cardiovascular risk factors in patients with first-episode psychosis in Sao Paulo, Brazil

Objective: The objective was to evaluate the cardiovascular profile of first-episode psychosis patients in Sao Paulo, Brazil, an issue that has not been sufficiently explored in low-/middle-income countries. Method: A cross-sectional study was performed 1 to 3 years after an initial, larger survey that assessed first-episode psychosis in sao Paulo. We evaluated cardiovascular risk factors and lifestyle habits using standard clinical examination and laboratory evaluation. Results: Of 151 contacted patients, 82 agreed to participate (mean age=35 years; 54% female). The following diagnoses were found: 20.7% were obese, 29.3% had hypertension, 39.0% had dyslipidemia, 19.5% had metabolic syndrome, and 1.2% had a >20% 10-year risk of coronary heart disease based on Framingham score. Also, 72% were sedentary, 25.6% were current smokers, and 7.3% reported a heavy alcohol intake. Conclusion: Compared to other samples, ours presented a distinct profile of higher rates of hypertension and diabetes (possibly due to dietary habits) and lower rates of smoking and alcohol intake (possibly due to higher dependence on social support). Indirect comparison vs. healthy, age-matched Brazilians revealed that our sample had higher frequencies of hypertension, diabetes and metabolic syndrome. Therefore, we confirmed a high cardiovascular risk in first-episode psychosis in Brazil. Transcultural studies are needed to investigate to which extent lifestyle contributes to such increased risk. (C) 2012 Elsevier Inc. All rights reserved.

Water use in a sugarcane plantation

The evapotranspiration (E) from a sugarcane plantation in the southeast Brazil was measured by the eddy-covariance method during two consecutive cycles. These represented the second (393 similar to days) and third year (374 similar to days) re-growth (ratoon). The total E in the first cycle was 829 similar to mm, accounting for 69% of rainfall, whereas in the second cycle, it was 690 similar to mm, despite the total rainfall (1353 similar to mm) being 13% greater. The ratio of E to available energy, the evaporative fraction, exhibited a smaller variation between the first and second cycles: 0.58 and 0.51, respectively. The estimated interception losses were 88 and 90 similar to mm, respectively, accounting for approximately 7% of the total rainfall. The sugarcane yield in the second cycle (61.5 similar to +/-similar to 4.0 similar to t similar to ha-1) was 26% lower than the first cycle, as well as lower than the regional average for the third ratoon (76 similar to t similar to ha-1). The below average yield was associated with less available soil water at the beginning of the cycle, with the amount of rainfall recorded during the first 120 similar to days of re-growth in the second cycle being 16% of that recorded in the first (203 similar to mm).

The Mechanism of Oocyte Activation Influences the Cell Cycle-Related Genes Expression During Bovine Preimplantation Development

The first cleavage divisions and preimplantation embryonic development are supported by mRNA and proteins synthesized and stored during oogenesis. Thus, mRNA molecules of maternal origin decrease and embryonic development becomes gradually dependent on expression of genetic information derived from the embryonic genome. However, it is still unclear what the role of the sperm cell is during this phase and whether the absence of the sperm cell during the artificial oocyte activation affects subsequent embryonic development. The objective of this study was to determine, in bovine embryos, changes in cell cycle-associated transcript levels (cyclin A, cyclin B, cyclin E, CDC2, CDK2, and CDK4) after oocyte activation in the presence or absence of the sperm cell. To evaluate that, in vitro-produced (IVP) and parthenogenetically activated (PA) embryos (2-4 cells (2-4C), 8-16 cells (8-16C) and blastocysts) were evaluated by real-time PCR. There was no difference in cleavage and blastocyst rates between IVP and PA groups. Transcript level was higher in oocytes than in IVP and PA embryos. Cleaved PA embryos showed higher expression of cyclin A, cyclin B, cyclin E, and CDK2 and lower expression of CDC2 when compared with that from the IVP group. At the time of activation, all transcripts were expressed less in PA than in IVP embryos, whereas at the blastocyst stage, almost all genes were expressed at a higher level in the PA group. These results suggest that in both groups there is an initial consumption of these transcripts in the early stages of embryonic development. Furthermore, 8-16C embryos seem to synthesize more cell cycle-related genes than 2-4C embryos. However, in PA embryos, activation of the cell cycle genes seems to occur after the 8- to 16-cell stage, suggesting a failure in the activation process.

BDNF gene polymorphism, cognition and symptom severity in a Brazilian population-based sample of first-episode psychosis subjects

OBJECTIVE: To investigate the influence of brain-derived neurotrophic factor (BDNF) gene variations on cognitive performance and clinical symptomatology in first-episode psychosis (FEP). METHODS: We performed BDNF val66met variant genotyping, cognitive testing (verbal fluency and digit spans) and assessments of symptom severity (as assessed with the PANSS) in a population-based sample of FEP patients (77 with schizophreniform psychosis and 53 with affective psychoses) and 191 neighboring healthy controls. RESULTS: There was no difference in the proportion of Met allele carriers between FEP patients and controls, and no significant influence of BDNF genotype on cognitive test scores in either of the psychosis groups. A decreased severity of negative symptoms was found in FEP subjects that carried a Met allele, and this finding reached significance for the subgroup with affective psychoses (p < 0.01, ANOVA). CONCLUSIONS: These results suggest that, in FEP, the BDNF gene Val66Met polymorphism does not exert a pervasive influence on cognitive functioning but may modulate the severity of negative symptoms.

Fluxes of CO2 above a sugarcane plantation in Brazil

Fluxes of CO2 were measured above a sugarcane plantation using the eddy-covariance method covering two growth cycles, representing the second and third re-growth (ratoons) harvested with stubble burning. The total net ecosystem exchange (NEE) in the first cycle (second ratoon, 393 days long) was −1964 ± 44 g C m−2; the gross ecosystem productivity (GEP) was 3612 ± 46 g C m−2 and the ecosystem respiration (RE) was 1648 ± 14 g C m−2. The NEE and GEP totals in the second cycle (third ratoon, 374 days long) decreased 51% and 25%, respectively and RE increased 7%. Accounting for the carbon emitted during biomass burning and the removal of stalks at harvest, net ecosystem carbon balance (NECB) totals were 102 ± 130 g C m−2 and 403 ± 84 g C m−2 in each cycle respectively. Thus the sugarcane agrosystem was approximately carbon neutral in the second ratoon. Yield in stalks fresh weight (SFW) attained the regional average (8.3 kg SFW m−2). Although it was a carbon source to the atmosphere, observed productivity (6.2 kg SFW m−2) of the third ratoon was 19% lower than the regional average due to the lower water availability observed during the initial 120 days of re-growth. However, the overall water use efficiency (WUE) achieved in the first cycle (4.3 g C kg−1 H2O) decreased only 5% in the second cycle. © 2013 Elsevier B.V. All rights reserved

Myc-mediated control of gene transcription in cancer cells

The Myc oncoproteins belong to a family of transcription factors composed by Myc, N-Myc and L-Myc. The most studied components of this family are Myc and N-Myc because their expressions are frequently deregulated in a wide range of cancers. These oncoproteins can act both as activators or repressors of gene transcription. As activators, they heterodimerize with Max (Myc associated X-factor) and the heterodimer recognizes and binds a specific sequence elements (E-Box) onto gene promoters recruiting histone acetylase and inducing transcriptional activation. Myc-mediated transcriptional repression is a quite debated issue. One of the first mechanisms defined for the Myc-mediated transcriptional repression consisted in the interaction of Myc-Max complex Sp1 and/or Miz1 transcription factors already bound to gene promoters. This interaction may interfere with their activation functions by recruiting co-repressors such as Dnmt3 or HDACs. Moreover, in the absence of , Myc may interfere with the Sp1 activation function by direct interaction and subsequent recruitment of HDACs. More recently the Myc/Max complex was also shown to mediate transcriptional repression by direct binding to peculiar E-box. In this study we analyzed the role of Myc overexpression in Osteosarcoma and Neuroblastoma oncogenesis and the mechanisms underling to Myc function. Myc overexpression is known to correlate with chemoresistance in Osteosarcoma cells. We extended this study by demonstrating that c-Myc induces transcription of a panel of ABC drug transporter genes. ABCs are a large family trans-membrane transporter deeply involved in multi drug resistance. Furthermore expression levels of Myc, ABCC1, ABCC4 and ABCF1 were proved to be important prognostic tool to predict conventional therapy failure. N-Myc amplification/overexpression is the most important prognostic factor for Neuroblastoma. Cyclin G2 and Clusterin are two genes often down regulated in neuroblastoma cells. Cyclin G2 is an atypical member of Cyclin family and its expression is associated with terminal differentiation and apoptosis. Moreover it blocks cell cycle progression and induces cell growth arrest. Instead, CLU is a multifunctional protein involved in many physiological and pathological processes. Several lines of evidences support the view that CLU may act as a tumour suppressor in Neuroblastoma. In this thesis I showed that N-Myc represses CCNG2 and CLU transcription by different mechanisms. • N-Myc represses CCNG2 transcription by directly interacting with Sp1 bound in CCNG2 promoter and recruiting HDAC2. Importantly, reactivation of CCNG2 expression through epigenetic drugs partially reduces N-Myc and HDAC2 mediated cell proliferation. • N-Myc/Max complex represses CLU expression by direct binding to a peculiar E-box element on CLU promoter and by recruitment of HDACs and Polycomb Complexes, to the CLU promoter. Overall our findings strongly support the model in which Myc overexpression/amplification may contribute to some aspects of oncogenesis by a dual action: i) transcription activation of genes that confer a multidrug resistant phenotype to cancer cells; ii), transcription repression of genes involved in cell cycle inhibition and cellular differentiation.

Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study

In older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission. The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin (GO) has shown antileukemic remission induction activity in patients with relapsed AML. Patients with AML or refractory anemia with excess blasts in first complete remission attained after intensive induction chemotherapy were randomized between 3 cycles of GO (6 mg/m(2) every 4 weeks) or no postremission therapy (control) to assess whether GO would improve outcome. The 2 treatment groups (113 patients receiving GO vs 119 control patients) were comparable with regard to age (60-78 years, median 67 years), performance status, and cytogenetics. A total of 110 of 113 received at least 1 cycle of GO, and 65 of 113 patients completed the 3 cycles. Premature discontinuation was mainly attributable to incomplete hematologic recovery or intercurrent relapse. Median time to recovery of platelets 50 x 10(9)/L and neutrophils 0.5 x 10(9)/L after GO was 14 days and 20 days. Nonhematologic toxicities were mild overall, but there was 1 toxic death caused by liver failure. There were no significant differences between both treatment groups with regard to relapse probabilities, nonrelapse mortality, overall survival, or disease-free survival (17% vs 16% at 5 years). Postremission treatment with GO in older AML patients does not provide benefits regarding any clinical end points. The HOVON-43 study is registered at The Netherlands Trial Registry (number NTR212) and at http://www.controlled-trials.com as ISRCTN77039377.

Pretreatment and outcome correlates of sexual and physical trauma in an epidemiological cohort of first-episode psychosis patients

High prevalence of trauma has been reported in psychosis. While role of trauma as a risk factor for developing psychosis is still debated, its negative impact on outcome has been described. Few studies have explored this issue in first-episode psychosis (FEP) patients. We assessed rate of stressful events, as well as premorbid and outcome correlates of past sexual and/or physical abuse (SPA) in an epidemiological FEP patients cohort.

Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial

This phase I trial was designed to develop a new effective and well-tolerated regimen for patients with aggressive B cell lymphoma not eligible for front-line anthracycline-based chemotherapy or aggressive second-line treatment strategies. The combination of rituximab (375 mg/m(2) on day 1), bendamustine (70 mg/m(2) on days 1 and 2), and lenalidomide was tested with a dose escalation of lenalidomide at three dose levels (10, 15, or 20 mg/day) using a 3 + 3 design. Courses were repeated every 4 weeks. The recommended dose was defined as one level below the dose level identifying ≥2/6 patients with a dose-limiting toxicity (DLT) during the first cycle. Thirteen patients were eligible for analysis. Median age was 77 years. WHO performance status was 0 or 1 in 12 patients. The Charlson Comorbidity Index showed relevant comorbidities in all patients. Two DLTs occurred at the second dose level (15 mg/day) within the first cycle: one patient had prolonged grade 3 neutropenia, and one patient experienced grade 4 cardiac adverse event (myocardial infarction). Additional grade 3 and 4 toxicities were as follows: neutropenia (31 %), thrombocytopenia (23 %), cardiac toxicity (31 %), fatigue (15 %), and rash (15 %). The dose of lenalidomide of 10 mg/day was recommended for a subsequent phase II in combination with rituximab 375 mg/m(2) on day 1 and bendamustine 70 mg/m(2) on days 1 and 2.

Consequences of depleted SERCA2-gated calcium stores in the skin

Sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) pumps belong to the family of Ca2+-ATPases responsible for the maintenance of calcium in the endoplasmic reticulum. In epidermal keratinocytes, SERCA2-controlled calcium stores are involved in cell cycle exit and onset of terminal differentiation. Hence, their dysfunction was thought to provoke impaired keratinocyte cohesion and hampered terminal differentiation. Here, we assessed cultured keratinocytes and skin biopsies from a canine family with an inherited skin blistering disorder. Cells from lesional and phenotypically normal areas of one of these dogs revealed affected calcium homeostasis due to depleted SERCA2-gated stores. In phenotypically normal patient cells, this defect compromised upregulation of p21(WAF1) and delayed the exit from the cell cycle. Despite this abnormality it failed to impede the terminal differentiation process in the long term but instead coincided with enhanced apoptosis and appearance of chronic wounds, suggestive of secondary mutations. Collectively, these findings provide the first survey on phenotypic consequences of depleted SERCA-gated stores for epidermal homeostasis that explain how depleted SERCA2 calcium stores provoke focal lesions rather than generalized dermatoses, a phenotype highly reminiscent of the human genodermatosis Darier disease.