Salacia campestris root bark extract: peroxidase inhibition, antioxidant and antiradical profile

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Clinical research on new drugs (Phase I). Profile of scientific publications: data from the pre-clinical phase and bioethical aspects

OBJETIVO: Traçar o perfil das publicações científicas de fase I e procurar saber se a publicação oferece dados da fase pré-clínica com ênfase nos aspectos bioéticos. MÉTODOS: Foram analisados 61 artigos científicos publicados no ano de 2007, que relatam pesquisas envolvendo seres humanos com novos fármacos, medicamentos ou vacinas em fase I. Foi elaborado um roteiro para coleta de dados, com o qual fosse possível analisar e avaliar os artigos científicos. O roteiro contempla itens referentes à fase pré-clínica (associados à fase clínica) e itens referentes às características da amostra. RESULTADOS: Nos artigos analisados, a maioria das pesquisas foi realizada nos EUA. Devido ao grande número de publicações destinadas às doenças oncológicas a maioria delas foi realizada com voluntários doentes. Quanto às informações sobre a fase pré-clínica presente nas publicações de fase I observamos que são pobres ou inexistentes. Mesmo que os autores julguem a pesquisa fase I como promissora e sugiram estudos futuros de fase II, ao leitor não é possível este mesmo julgamento pela escassez de informações da fase pré-clínica. CONCLUSÃO: O perfil das publicações levanta dados que merecem reflexão e análise para melhor avaliação do que está ocorrendo com as publicações de fase I.

Heavy metals in Oxisols amended with biosolids and cropped with maize in a long-term experiment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Self-consistent equilibrium calculation through a direct variational technique in tokamak plasmas

A self-consistent equilibrium calculation, valid for arbitrary aspect ratio tokamaks, is obtained through a direct variational technique that reduces the equilibrium solution, in general obtained from the 2D Grad-Shafranov equation, to a 1D problem in the radial flux coordinate rho. The plasma current profile is supposed to have contributions of the diamagnetic, Pfirsch-Schluter and the neoclassical ohmic and bootstrap currents. An iterative procedure is introduced into our code until the flux surface averaged toroidal current density (J(T)), converges to within a specified tolerance for a given pressure profile and prescribed boundary conditions. The convergence criterion is applied between the (J(T)) profile used to calculate the equilibrium through the variational procedure and the one that results from the equilibrium and given by the sum of all current components. The ohmic contribution is calculated from the neoclassical conductivity and from the self-consistently determined loop voltage in order to give the prescribed value of the total plasma current. The bootstrap current is estimated through the full matrix Hirshman-Sigmar model with the viscosity coefficients as proposed by Shaing, which are valid in all plasma collisionality regimes and arbitrary aspect ratios. The results of the self-consistent calculation are presented for the low aspect ratio tokamak Experimento Tokamak Esferico. A comparison among different models for the bootstrap current estimate is also performed and their possible Limitations to the self-consistent calculation is analysed.

Genetic profile characterization of 10 X-STRs in four populations of the southeastern region of Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Profile of Maytenus aquifolium action over free radicals and reactive oxygen species

Reactive oxygen species (ROS) and free radical species have been implicated in initiating, accompanying or causing many diseases in living organisms; there is thus, a continual need for antioxidants molecules to inactivate ROS/free radicals. Many studies of plants crude extracts have demonstrated free-radical scavenging and antioxidant action. Maytenus species have long been used, in several countries, as traditional medicines against gastric ulcers, dyspepsia and others gastric problems and for their anti-inflammatory properties. In this study, Maytenus aquifolium (Celastraceae) root bark ethanol extract was assessed for its ability to scavenge free radicals and reactive oxygen species. The results were expressed as percentage inhibition of the active species. The extract was efficient against studied reactive species: DPPH radical (obtained inhibition = 35.5 ± 1.3 %), ABTS.+ (IC50 = 0.0036 ± 0.0003 mg/mL), HOCl (IC50 = 0.002 ± 0.0001 mg/mL), O2 .- (obtained inhibition = 36.0 ± 2.1 %), and NO. (obtained inhibition = 18.3 ± 0.4 %). Uniterms Oxidant species Free radicals Maytenus aquifolium Oxidative damage.

Pharmacokinetic Profile of A New Diclofenac Prodrug without Gastroulcerogenic Effect

Gastrotoxicity is a major problem for long-term therapy with non-steroidal anti-inflammatory drugs (NSAIDs). DICCIC (1-(2,6-dichlorophenyl)indolin-2-one) is a new diclofenac prodrug, which has proven anti-inflammatory activity without gastroulcerogenic effect. The aim of this work was to compare the pharmacokinetic profiles of diclofenac from DICCIC (7.6 mg/kg equivalent to 8.1 mg/kg diclofenac) and diclofenac (8.1 mg/kg) administration in Wistar rats weighing 250-300 g (n=20). The doses were calculated by interspecific allometric scaling based on the 2 mg/kg from diary human dose of diclofenac. Blood samples were collected in heparinized tubes via the femoral artery through the implanted catheter. The plasma was separated and quantitation was made in a HPLC system with a UV-Vis detector. The confidence limits of the bioanalytical method were appropriate for its application in a preclinical pharmacokinetic study. The AUC of diclofenac from DICCIC (53.7± 5.8 ug/mL.min) was significantly less (Mann Whitney test, p<0.05) than that of diclofenac from diclofenac administration (885.9 ± 124,8 ug/mL.min). Terminal half-life of diclofenac from DICCIC (50.1 ± 17.2 min) was significantly less (Mann Whitney test, p<0.05) than that of diclofenac from diclofenac administration (247.4 ± 100.9 min). Still the parameters clearance and distribution volume were calculated for diclofenac from diclofenac, whose results were 9.2 ±1.2 mL/min.kg and 3.3 ±1.2 L/kg, respectively. The results of DICCIC from DICCIC administration were 108.9 ± 19.6 mL/min.kg and 7.8 ± 2.4 L/kg for clearance and distribution volume, respectively. The pharmacokinetic profile demonstrated that there was an increase in diclofenac elimination and a lower exposure to diclofenac with administration of DICCIC compared to diclofenac. © 2013 Bentham Science Publishers.

Qualidade do café natural e despolpado em diferentes condições de secagem e tempos de armazenamento

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A comprehensive study on the phenolic profile of widely used culinary herbs and spices: Rosemary, thyme, oregano, cinnamon, cumin and bay

Herbs and spices have long been used to improve the flavour of food without being considered as nutritionally significant ingredients. However, the bioactive phenolic content of these plant-based products is currently attracting interest.In the present work, liquid chromatography coupled to high-resolution/accurate mass measurement LTQ-Orbitrap mass spectrometry was applied for the comprehensive identification of phenolic constituents of six of the most widely used culinary herbs (rosemary, thyme, oregano and bay) and spices (cinnamon and cumin). In this way, up to 52 compounds were identified in these culinary ingredients, some of them, as far as we know, for the first time. In order to establish the phenolic profiles of the different herbs and spices, accurate quantification of the major phenolics was performed by multiple reaction monitoring in a triple quadrupole mass spectrometer. Multivariate statistical treatment of the results allowed the assessment of distinctive features among the studied herbs and spices. (C) 2014 Elsevier Ltd. All rights reserved.

Exogenous bacterial osteomyelitis in 52 dogs: a retrospective study of etiology and in vitro antimicrobial susceptibility profile (2000-2013)

Background: Most clinical cases of osteomyelitis in dogs involve infectious agents, especially bacteria and fungi. The characterization of these microorganisms may aid in the prevention and treatment of disease.Objective: The aim of this study was to evaluate retrospectively microbiological cultures and in vitro antimicrobial susceptibility profile of isolates from 52 cases of bacterial osteomyelitis in long bones of dogs over 2000-2013. In 78% of the cases injuries were caused by a motor vehicle accident, but there were a few cases of dog bites (17%) and ascending infection due to pododermatitis (5%).Animals and methods: The isolated microorganisms were identified based on conventional phenotypic methods. In vitro disk diffusion test was performed using 30 different antimicrobials.Results: The isolates were obtained from femur (28%), humerus (16%), tibia (31%), and radius/ulna (25%). Among 52 cases, culture was positive in 88% of cases. Thirteen genus of different species of microorganisms were isolated. The most common microorganisms isolated were Staphylococcus spp. and Escherichia coli followed by Streptococcus spp., enteric bacteria, Corynebacterium sp. and anaerobic bacteria. In 42% of cases cultures were mixed. The most effective drugs against isolated bacteria were amoxicillin and clavulanate potassium (79%) followed by ceftriaxone (69%). High-resistance rates were documented against azithromycin (80%), penicillin (59%), and clindamycin (59%).Conclusions: The present study highlights diverse etiologic agents in cases of infectious bacterial osteomyelitis, with predominance of Staphylococcus genus, and reinforces the importance of obtaining cultures and susceptibility profiles given the high rates of antimicrobial resistance.

Impact of Glucocorticoid Receptor Gene Polymorphisms on the Metabolic Profile of Adult Patients with the Classical Form of 21-Hydroxylase Deficiency

Background: CAH patients have an increased risk of cardiovascular disease, and it remains unknown if lifelong glucocorticoid (GC) treatment is a contributing factor. In the general population, glucocorticoid receptor gene (NR3C1) polymorphisms are associated with an adverse metabolic profile. Our aim was to analyze the association between the NR3C1 polymorphisms and the metabolic profile of CAH patients. Methodology: Sixty-eight adult patients (34SV/34SW) with a mean age of 28.4 +/- 9 years received dexamethasone (mean 0.27 +/- 0.11 mg/day) to obtain normal androgen levels. SW patients also received fludrocortisone (50 mu g/day). Metabolic syndrome (MetS) was defined by the NCEP ATPIII criteria and obesity by BMI >= 30 kg/m(2). NR3C1 alleles were genotyped, and association analyses with phenotype were carried out with Chi-square, t-test and regression analysis. Results: Obesity and MetS were observed in 23.5% and 7.3% of patients, respectively, and were not correlated with GC doses and treatment duration. BMI was positively correlated with blood pressure (BP), triglycerides (TG), LDL-c levels and HOMA-IR and inversely correlated with HDL-c levels. BclI and A3669G variants were found in 26.4% and 9.6% of alleles, respectively. Heterozygotes for the BclI polymorphism presented with higher BMI (29 kg/m(2) +/- 5.3 vs. 26 kg/m(2) +/- 5.3, respectively) and waist circumference (89 cm +/- 12.7 vs. 81 cm +/- 13, respectively) compared to wild-type subjects. Hypertension was found in 12% of patients and heterozygotes for the BclI polymorphism presented higher systolic BP than wild type subjects. Low HDL-c and high TG levels were identified in 30% and 10% of patients, respectively, and were not associated with the NR3C1 polymorphisms. A3669G carriers and non-carriers did not differ. Conclusion: In addition to GC therapy, the BclI GR variant might play an important role in obesity susceptibility in CAH patients. Genotyping of GR polymorphisms could result in the identification of a subgroup at risk patients, allowing for the establishment of personalized treatment and the avoidance of long-term adverse consequences.

Divertor map with freedom of geometry and safety factor profile

An explicit, area-preserving and integrable magnetic field line map for a single-null divertor tokamak is obtained using a trajectory integration method to represent equilibrium magnetic surfaces. The magnetic surfaces obtained from the map are capable of fitting different geometries with freely specified position of the X-point, by varying free model parameters. The safety factor profile of the map is independent of the geometric parameters and can also be chosen arbitrarily. The divertor integrable map is composed of a nonintegrable map that simulates the effect of external symmetry-breaking resonances, so as to generate a chaotic region near the separatrix passing through the X-point. The composed field line map is used to analyze escape patterns (the connection length distribution and magnetic footprints on the divertor plate) for two equilibrium configurations with different magnetic shear profiles at the plasma edge.

LONG TIME CORRELATIONS OF NONLINEAR LUTTINGER LIQUIDS

An overview is given of the limitations of Luttinger liquid theory in describing the real time equilibrium dynamics of critical one-dimensional systems with nonlinear dispersion relation. After exposing the singularities of perturbation theory in band curvature effects that break the Lorentz invariance of the Tomonaga-Luttinger model, the origin of high frequency oscillations in the long time behaviour of correlation functions is discussed. The notion that correlations decay exponentially at finite temperature is challenged by the effects of diffusion in the density-density correlation due to umklapp scattering in lattice models.

STRUCTURE AND DYNAMICS: THE TRANSITION FROM NONEQUILIBRIUM TO EQUILIBRIUM IN INTEGRATE-AND-FIRE DYNAMICS

The transient and equilibrium properties of dynamics unfolding in complex systems can depend critically on specific topological features of the underlying interconnections. In this work, we investigate such a relationship with respect to the integrate-and-fire dynamics emanating from a source node and an extended network model that allows control of the small-world feature as well as the length of the long-range connections. A systematic approach to investigate the local and global correlations between structural and dynamical features of the networks was adopted that involved extensive simulations (one and a half million cases) so as to obtain two-dimensional correlation maps. Smooth, but diverse surfaces of correlation values were obtained in all cases. Regarding the global cases, it has been verified that the onset avalanche time (but not its intensity) can be accurately predicted from the structural features within specific regions of the map (i.e. networks with specific structural properties). The analysis at local level revealed that the dynamical features before the avalanches can also be accurately predicted from structural features. This is not possible for the dynamical features after the avalanches take place. This is so because the overall topology of the network predominates over the local topology around the source at the stationary state.

Soft tissue profile changes after rapid maxillary expansion with a bonded expander

The aim of this study was to evaluate the short-and long-term treatment effects of rapid maxillary expansion (RME) on the soft tissue facial profile of subjects treated with a modified acrylic-hyrax device. The sample comprised 10 males and 10 females in the mixed dentition. Their average age was 9.3 years +/- 10 months pre-treatment (T1), with a narrow maxilla and posterior crossbite, treated with a modified fixed maxillary expander with an occlusal splint. Lateral cephalometric radiographs obtained at T1, immediately post-expansion (T2), and after retention (T3) were used to determine possible changes in the soft tissue facial profile. The means and standard deviations for linear and angular cephalometric measurements were analysed statistically using analysis of variance and Tukey's test (alpha = 0.05). The measurements at T2 differed significantly from those at T1 and T3. However, RME did not produce any statistically significant alteration (P > 0.05) in the soft tissue profile for any of the cephalometric landmarks evaluated when compared at T1 and T3. The use of a fixed expander associated with an occlusal splint did not cause significant alterations in the soft tissue facial profile at T3. This modified device is effective for preventing the adverse vertical effects of RME such as an increase anterior face height in patients with a crossbite.