Efficacy and Tolerability of the Combination Valsartan/Hydrochlorothiazide Compared with Amlodipine in a Mild-to-moderately Hypertensive Brazilian Population

Most hypertensive patients need more than one drug to reach recommended blood-pressure targets. We investigated the effects on 24-h ambulatory blood pressure (ABP) of the angiotensin-receptor blocker, valsartan, in combination with hydrochlorothiazide (HCTZ), compared with the calcium-channel blocker amlodipine in a Brazilian population in a multicentre, double-blind, double-dummy, parallel group, controlled study in 373 patients with essential hypertension. After a 2-week washout period, patients with a mean sitting systolic blood pressure (SBP) of 160-190 mmHg were randomized to receive either valsartan 160 mg o.d., or amlodipine 5 mg o.d. for 2 weeks and subsequently force-titrated to valsartan 160 mg/HCTZ 25 mg o.d. or amlodipine 10 mg o.d. This regimen was continued until the end of the study at week 8. The primary efficacy parameter was the change from baseline to week 8 in mean 24-h SBP. Secondary endpoints were change in mean 24-h diastolic blood pressure (DBP), tolerability and safety of treatments. Valsartan/HCTZ achieved a mean reduction in systolic ABP of -19.1 ± 11.3 mmHg compared with -20.7 ± 12.0 mmHg with amlodipine (p = 0.324 for the comparison) and in diastolic ABP by -11.1 ± 7.4 mmHg vs -11.6 ± 7.2 mmHg by amlodipine (p = 0.853 for the comparison). The valsartan/HCTZ group exhibited markedly lower rates of adverse events and discontinuations than the amlodipine group. Peripheral oedemas were far more frequent with amlodipine than with valsartan/HCTZ (1.6% with valsartan/HCTZ; 16.8% with amlodipine). Thus, the valsartan 160 mg/HCTZ 25 mg combination appears to be as efficacious as amlodipine 10 mg in this patient population but better tolerated.

Search for the flavor-changing neutral current decay Bs 0 → μ+ μ- pp̄ Collisions at √s = 1.96 TeV with the DO Detector

We present the results of a search for the flavor-changing neutral current decay Bs 0 → μ+ μ-. using a data set with integrated luminosity of 240 pb-1 of pp̄ collisions at √s = 1.96 TeV collected with the D0 detector in run II of the Fermilab Tevatron collider. We find the upper limit on the branching fraction to be B(Bs 0 → μ+ π-) ≤ 5.0 × 10-7 at the 95% C.L. assuming no contributions from the decay Bd 0 → μ+ μ- in the signal region. This limit is the most stringent upper bound on the branching fraction Bs 0 → μ+ μ- to date. © 2005 The American Physical Society.

Dornase alfa improves the health-related quality of life among Brazilian patients with cystic fibrosis - A one-year prospective study

Background: Health-related quality of life (HRQOL) measurements provide valuable information about the psychological and social impact of treatment on patients with cystic fibrosis (CF). This study evaluated the HRQOL of Brazilian patients with CF and assessed the changes in HRQOL domains over 1 year after dornase alfa (Pulmozyme) introduction. Patients and Methods: One hundred fifty-six stable patients with CF and 89 caregivers answered the Portuguese-validated version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at baseline (T 0), and at 3 (T 1), 6 (T 2), 9 (T 3), and 12 (T 4) months of follow-up. Eighteen patientswere excluded because they did not fulfill the inclusion criteria. The patients were analyzed in two groups: those aged 6-11 years and those aged 14 years and older. ANOVA for observed repeated results and the last observation carried forward (LOCF) method for missing data were used for the statistical analysis. Results: After 1 year of follow-up, there was significant improvement in respiratory symptoms (T 4-T 0=8.1; 95% confidence interval (95% CI)=[2.1;14.0]; effect size (ES)=0.35; P<0.001), Emotional Functioning (T 4-T 0=5.6; 95% CI=[1.1;10.1]; ES=0.31; P<0.05), Social Functioning (T 4-T 0=6.0; 95% CI=[1.3;11.7]; ES=0.31; P<0.05), Body Image (T 4-T 0=11.9; 95% CI=[4.1;19.7]; ES=0.42; P<0.05), and Treatment Burden (T 4-T 0=5.3; 95% CI=[0.3;10.3]; ES=0.24; P<0.05) domains in the younger group. A significant improvement in Role Functioning (T 4-T 0=6.1; 95% CI=[1.1;11.1]; ES=0.40; P<0.05), Body Image (T 4-T 0=12.6; 95% CI=[3.5;21.7]; ES=0.46; P<0.05), and Weight (T 4-T 0=11.7; 95% CI=[1.8;21.6]; ES=0.40; P<0.05) was obtained in the older group. The caregivers' CFQ-R showed improvements in the Digestive Symptoms (T 4-T 0=5.5; 95% CI=[1.5;9.4]; ES=0.30; P<0.05), Respiratory Symptoms (T 4-T 0=7.6; 95% CI=[3.9;11.4]; ES=0.48; P<0.05), and Weight (T 4-T 0=10.1; 95% CI=[1.6;18.6]; ES=0.26; P<0.05) domains. Conclusion: The introduction of dornase alfa improved the HRQL of the patients with CF during the first year of treatment. © 2010 Wiley-Liss, Inc.

Frequency of multiple endocrine neoplasia type 1 in a group of patients with pituitary adenoma: genetic study and familial screening

The purpose of this study it was to evaluate the frequency of Multiple Endocrine Neoplasia type 1 (MEN1) in patients with pituitary adenoma and to perform genetic analysis and familial screening of those individuals afflicted with MEN1. 144 patients with pituitary adenoma at Botucatu Medical School, UNESP-Univ Estadual Paulista, were assessed retrospectively for MEN1 during the years of 2005-2011. The patients were evaluated for the presence of primary hyperparathyroidism (PHP) and enteropancreatic tumors. Genetic analysis was performed for the individuals with clinically diagnosed MEN1. Thirteen patients met the diagnostic criteria for MEN1, but three individuals belong to the same family and they were considered as a single MEN1 event, revealing 7.7 % frequency of MEN1 in this patient group. Genetic analysis showed MEN1 mutations in four index cases: IVS4+1 G>A, IVS3-6 C>T, c.1547insC and a new D180A mutation. One patient did not agree to participate in the genetic study and another one was referred for follow up in other hospital. Only polymorphisms were found in the other individuals, one of which was novel. We identified a high frequency of MEN1 in pituitary adenoma patients. Since PHP is one of the most common MEN1 tumor and patients are mostly asymptomatic, we suggest that all pituitary adenoma patients have their calcium profile analyzed. © 2013 Springer Science+Business Media New York.

Braneworlds scenarios in a gravity model with higher order spatial three-curvature terms

In this work we study a Hořava-like 5-dimensional model in the context of braneworld theory. The equations of motion of such model are obtained and, within the realm of warped geometry, we show that the model is consistent if and only if λ takes its relativistic value 1. Furthermore, we show that the elimination of problematic terms involving the warp factor second order derivatives are eliminated by imposing detailed balance condition in the bulk. Afterwards, Israel's junction conditions are computed, allowing the attainment of an effective Lagrangian in the visible brane. In particular, we show that the resultant effective Lagrangian in the brane corresponds to a (3 + 1)-dimensional Hořava-like model with an emergent positive cosmological constant but without detailed balance condition. Now, restoration of detailed balance condition, at this time imposed over the brane, plays an interesting role by fitting accordingly the sign of the arbitrary constant β, insuring a positive brane tension and a real energy for the graviton within its dispersion relation. Also, the brane consistency equations are obtained and, as a result, the model admits positive brane tensions in the compactification scheme if, and only if, β is negative and the detailed balance condition is imposed. © 2013 Springer-Verlag Berlin Heidelberg and Società Italiana di Fisica.

The Deoxyhypusine Synthase Mutant dys1-1 Reveals the Association of eIF5A and Asc1 with Cell Wall Integrity

The putative eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein among archaea and eukaryotes that has recently been implicated in the elongation step of translation. eIF5A undergoes an essential and conserved posttranslational modification at a specific lysine to generate the residue hypusine. The enzymes deoxyhypusine synthase (Dys1) and deoxyhypusine hydroxylase (Lia1) catalyze this two-step modification process. Although several Saccharomyces cerevisiae eIF5A mutants have importantly contributed to the study of eIF5A function, no conditional mutant of Dys1 has been described so far. In this study, we generated and characterized the dys1-1 mutant, which showed a strong depletion of mutated Dys1 protein, resulting in more than 2-fold decrease in hypusine levels relative to the wild type. The dys1-1 mutant demonstrated a defect in total protein synthesis, a defect in polysome profile indicative of a translation elongation defect and a reduced association of eIF5A with polysomes. The growth phenotype of dys1-1 mutant is severe, growing only in the presence of 1 M sorbitol, an osmotic stabilizer. Although this phenotype is characteristic of Pkc1 cell wall integrity mutants, the sorbitol requirement from dys1-1 is not associated with cell lysis. We observed that the dys1-1 genetically interacts with the sole yeast protein kinase C (Pkc1) and Asc1, a component of the 40S ribosomal subunit. The dys1-1 mutant was synthetically lethal in combination with asc1Δ and overexpression of TIF51A (eIF5A) or DYS1 is toxic for an asc1Δ strain. Moreover, eIF5A is more associated with translating ribosomes in the absence of Asc1 in the cell. Finally, analysis of the sensitivity to cell wall-perturbing compounds revealed a more similar behavior of the dys1-1 and asc1Δ mutants in comparison with the pkc1Δ mutant. These data suggest a correlated role for eIF5A and Asc1 in coordinating the translational control of a subset of mRNAs associated with cell integrity. © 2013 Galvão et al.

Rheological behavior of binary aqueous solutions of poly(ethylene glycol) of 1500 g·mol-1 as affected by temperature and polymer concentration

The rheological behavior of poly(ethylene glycol) of 1500 g·mol -1(PEG1500) aqueous solutions with various polymer concentrations (w = 0.05, 0.10, 0.15, 0.20 and 0.25) was studied at different temperatures (T = 283.15, 288.15, 293.15, 298.15 and 303.15) K. The analyses were carried out considering shear rates ranging from (20 to 350) s-1, using a cone-and-plate rheometer under controlled stress and temperature. Classical rheological models (Newton, Bingham, Power Law, Casson, and Herschel-Bulkley) were tested. The Power Law model was shown suitable to mathematically represent the rheological behavior of these solutions. Well-adjusted empirical models were derived for consistency index variations in function of temperature (Arrhenius-type model; R2 > 0.96), polymer concentration (exponential model; R2 > 0.99) or the combination of both (R 2 > 0.99). Additionally, linear models were used to represent the variations of behavior index in the functions of temperature (R2 > 0.83) and concentration (R2 > 0.87). © 2013 American Chemical Society.

Early endosome antigen 1 (EEA1) decreases in macrophages infected with Paracoccidioides brasiliensis

Paracoccidioidomycosis (PCM) is a chronic granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis, endemic in Latin America. P. brasiliensis has been observed in epithelial cells in vivo and in vitro, as well as within the macrophages. The identification of the mechanism by which it survives within the host cell is fertile ground for the discovery of its pathogenesis since this organism has the ability to induce its own endocytosis in epithelial cells and most likely in macrophages. The study of the expression of endocytic proteins pathway and co-localization of microorganisms enable detection of the mechanism by which microorganisms survive within the host cell. The aim of this study was to evaluate the expression of the endocytic protein EEA1 (early endosome antigen 1) in macrophages infected with P. brasiliensis. For detection of EEA1, three different techniques were employed: immunofluorescence, real-time polymerase chain reaction (PCR) and immunoblotting. In the present study, decreased expression of EEA1 as well as the rearrangement of the actin was observed when the fungus was internalized, confirming that the input mechanism of the fungus in macrophages occurs through phagocytosis. © 2013 ISHAM.

Alteração da expressão da Anexina-A1 e Galectina-1 na progressão do câncer colorretal esporádico

Pós-graduação em Genética - IBILCE

Restricted stimulus control in stimulus control shaping with a capuchin monkey

Teaching the first instances of arbitrary matching-to-sample to nonhumans can prove difficult and time consuming. Stimulus control relations may develop that differ from those intended by the experimentereven when stimulus control shaping procedures are used. We present, in this study, efforts to identify sources of shaping program failure with a capuchin monkey. Procedures began with a baseline of identity matching. During subsequent shaping trials, compound comparison stimuli had two componentsone identical to and another different from the sample. The identical component was eliminated gradually by removing portions across trials (i.e., subtracting stimulus elements). The monkey performed accurately throughout shaping. At a late stage in the program, probe tests were conducted: (1) arbitrary matching trials that had all elements of the identical comparison removed and (2) other trials that included residual elements. During the test, the monkey performed at low levels on the former trials and higher levels on the latter. These results suggested that higher accuracy was due merely to continued control by the residual elements: the target arbitrary matching relations had not been learned. Thus, it appears that procedures that gradually transform identity matching baselines into arbitrary matching can fail by inadvertently shaping restricted control by residual elements. Subsequent probes at the end of the shaping series showed a successful transfer of stimulus control from identity to arbitrary matching after further programming steps apparently overcame the restricted stimulus control.

Mudanças no perfil facial de crianças com má oclusão classe II, divisão 1 decorrentes do crescimento normal e induzidas pelo bionator de Balters

Pós-graduação em Odontologia - FOAR

Relação do índice bispetral e da taxa de supressão do traçado do eletroencefalograma com disfunção cognitiva pós-operatória em cirurgia de revascularização do miocárdio

Pós-graduação em Anestesiologia - FMB

Oral microbial colonization in children with sickle cell anaemia under long-term prophylaxis with penicillin

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Elevated micronucleus frequency in patients with type 2 diabetes, dyslipidemia and periodontitis

The over-production of reactive oxygen species (ROS) can cause oxidative damage to a large number of molecules, including DNA, and has been associated with the pathogenesis of several disorders, such as diabetes mellitus (DM), dyslipidemia and periodontitis (PD). We hypothesise that the presence of these diseases could proportionally increase the DNA damage. The aim of this study was to assess the micronucleus frequency (MNF), as a biomarker for DNA damage, in individuals with type 2 DM, dyslipidemia and PD. One hundred and fifty patients were divided into five groups based upon diabetic, dyslipidemic and periodontal status (Group 1 - poor controlled DM with dyslipidemia and PD; Group 2 - well-controlled DM with dyslipidemia and PD; Group 3 - without DM with dyslipidemia and PD; Group 4 - without DM, without dyslipidemia and with PD; and Group 5 - without DM, dyslipidemia and PD). Blood analyses were carried out for fasting plasma glucose, HbA1c and lipid profile. Periodontal examinations were performed, and venous blood was collected and processed for micronucleus (MN) assay. The frequency of micronuclei was evaluated by cell culture cytokinesis-block MN assay. The general characteristics of each group were described by the mean and standard deviation and the data were submitted to the Mann-Whitney, Kruskal-Wallis, Multiple Logistic Regression and Spearman tests. The Groups 1, 2 and 3 were similarly dyslipidemic presenting increased levels of total cholesterol, low density lipoprotein cholesterol and triglycerides. Periodontal tissue destruction and local inflammation were significantly more severe in diabetics, particularly in Group 1. Frequency of bi-nucleated cells with MN and MNF, as well as nucleoplasmic bridges, were significantly higher for poor controlled diabetics with dyslipidemia and PD in comparison with those systemically healthy, even after adjusting for age, and considering Bonferroni's correction. Elevated frequency of micronuclei was found in patients affected by type 2 diabetes, dyslipidemia and PD. This result suggests that these three pathologies occurring simultaneously promote an additional role to produce DNA impairment. In addition, the micronuclei assay was useful as a biomarker for DNA damage in individuals with chronic degenerative diseases.