Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells

Immunosuppressive drugs are used to suppress immune system activity in transplant patients and reduce the risk of organ rejection. The present study evaluated the potential cytotoxic, genotoxic and mutagenic of the immunosuppressive drugs cyclosporine (CsA) and tacrolimus (FK-506) on normal human fibroblasts (MRC-5 cells). Based on plasma concentrations of the immunosuppressive drugs, which were obtained from the records of kidney transplant patients at the Kidney Institute of Londrina, Brazil, 11 concentrations of each immunosuppressive were chosen to evaluate cell viability using the MIT assay. From these results, CsA and FK-506 concentrations of 135, 300, 675, and 1520 ng/ml and 8, 16, 24, and 32 ng/ml, respectively, were evaluated using (i) the comet assay, (ii) the nuclear division index (NDI), (iii) the micronucleus test (CBMN) and (iv) cell proliferation curves generated by quantifying cell numbers and protein levels. In this study, 1520 to 3420 ng/ml CsA decreased cell viability after 48 h of exposure. Genotoxic effects were observed only with a concentration of 1520 ng/ml after 3 h of exposure and with concentrations of 675 and 1520 ng/ml after 24 h of exposure. Mutagenic effects were observed only for the concentration of 1520 ng/ml. FK-506 decreased cell viability after 72 h of exposure for concentrations up to 20 ng/ml; genotoxic effects were observed with concentrations up to 8 ng/ml for both treatment times (3 and 24 h) and mutagenic effects were observed with concentrations of 24 and 32 ng/ml after 24 h of treatment. The cell proliferation curves demonstrated the absence of cytostatic effects of these drugs, and these data were confirmed by the NDI analysis. Our results suggest that concentrations lower than 300 ng/ml of CsA and 16 ng/ml of FK-506 are safe for use, as they did not induce genotoxic and mutagenic damage or affect MRC-5 cell viability and proliferation. (C) 2014 Elsevier GmbH. All rights reserved.

O índice BODE reflete o nível de atividade física na vida diária de pacientes com DPOC?

Objectives: To study the relationship between the level of physical activity in daily life and disease severity assessed by the BODE index in patients with chronic obstructive pulmonary disease (COPD). Methods: Sixty-seven patients with COPD (36 men) with forced expiratory volume in the first second (FEV(1)) of 39 (27-47)% predicted and age of 66 (61-72) years old were evaluated by spirometry, dyspnea levels (measured by the Medical Research Council scale, MRC) and by the 6-minute walking test (6MWT). The BODE index was calculated based on the body mass index (weight/height(2)), FEV(1), MRC and 6MWT, and then the patients were divided in four quartiles according to their scores (Quartile I: 0 to 2 points, n=15; Quartile II: 3 to 4 points, n=20; Quartile III: 5 to 6 points, n=23; Quartile IV: 7 to 10 points, n=9). Two activity monitors (DynaPort (R) and SenseWear (R)) were used to evaluate the level of physical activity in daily life. The Kruskal-Wallis test (Dunns's post-hoc test), the Mann-Whitney test and the Spearman Correlation Coefficient were used for statistical analysis. Results: There were modest correlation between the BODE index and the time spent walking per day, the total daily energy expenditure and the time spent in moderate and vigorous activities per day (-0.32 <= r <=- 0.47; p <= 0.01 for all variables). When comparing the pooled quartiles I+II with III+IV, there were significant difference between the time spent walking per day, the total daily energy expenditure and the time spent in moderate activities per day (p <= 0.05). Conclusion: The level of physical activity in daily life has a modest correlation with the classification of COPD severity assessed by the BODE index, reflecting only differences between patients with classified as mild-moderate and severe-very severe COPD.

Desempenho agronômico da cultura do milho e espécies forrageiras em sistema de Integração Lavoura-Pecuária no Cerrado

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

Three-year follow-up study of respiratory and systemic manifestations of chronic obstructive pulmonary disease

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

Perfil do nível de atividade física na vida diária de pacientes portadores de DPOC no Brasil

Objective: To evaluate characteristics of physical activities in daily life in COPD patients in Brazil, correlating those Characteristics with physiological variables. Methods: Physical activities in daily life were evaluated in 40 COPD patients (18 males; 66 +/- 8 years of age; FEV(1) = 46 +/- 16 % of predicted; body mass index = 27 +/- 6 kg/m(2)) and 30 healthy age- and gender-matched subjects, using a multiaxial accelerometer-based sensor for 12 h/day on two consecutive days. We also assessed maximal and functional exercise capacity, using the incremental exercise test and the six-minute walk test (6MWT), respectively; MIP and MEP; peripheral muscle force, using the one-repetition maximum test and the handgrip test; quality of life, using the Saint George's Respiratory Questionnaire (SGRQ); functional status, using the London Chest Activity of Daily Living questionnaire; and dyspnea sensation, using the Medical Research Council (MRC) scale. Results: Mean walking time/day was shorter for COPD patients than for the controls (55 +/- 33 vs. 80 +/- 28 min/day; p = 0.001), as movement intensity was lower (1.9 +/- 0.4 vs. 2.3 +/- 0.6 m/s(2); p = 0.004). The COPD patients also tended to spend more time seated (294 +/- 114 vs. 246 +/- 122 min/day, p = 0.08). Walking time/day correlated with the 6MWT (r = 0.42; p = 0.007) and maximal workload (r = 0.41; p = 0.009), as well as with age, MRC scale score and SGRQ activity domain score (-0.31 <= r <= -0.43; p <= 0.05 for all). Conclusions: This sample of Brazilian patients with COPD, although more active than those evaluated in studies conducted in Europe, were less active than were the controls. Walking time/day correlated only moderately with maximal and functional exercise capacity.

A theoretical analysis on electronic structure of the (110) surface of TiO2-SnO2 mixed oxide

Mixed oxide compounds, such as TiO2-SnO2 system are widely used as gas sensors and should also provide varistor properties modifying the TiO2 surface. Therefore, a theoretical investigation has been carried out characterizing the effect of SnO2 on TiO2 addition on the electronic structure by means of ab initio SCF-LCAO calculations using all electrons. In order to take into account the finite size of the cluster, we have used the point charge model for the (TiO2)(15) cluster to study the effect on electronic structure of doping the TiO2 (110) Surface. The contracted basis set for titanium (4322/42/3), oxygen (33/3) and tin (43333/4333/43) atoms were used. The charge distributions, dipole moments, and density of states of doping TiO2 and vacancy formation are reported and analysed. (C) 2003 Elsevier B.V. All rights reserved.

Effect of oxidizing and reducing atmospheres on the electrical properties of dense SnO2-based varistors

The SnO2 based varistor systems recently presented in the literature appear to have a promising potential in commercial applications. Experimental evidence shows that there is a dependence of nonlinear constant values with thermal treatment under different atmospheres. Thermal treatments in oxygen and nitrogen rich atmospheres at 900 degreesC prove this dependence, indicating that the nonlinear constant values are significantly lower when the material is submitted to a nitrogen atmosphere. Moreover, electrical properties can be restored when the varistor is subjected to thermal treatment at the same temperature in an oxygen atmosphere, indicating that the mechanism seems to be reversible. This paper discusses this behavior focusing in the grain boundary region. Ta2O5 mol% concentrations are also analyzed and the results indicate an optimum Ta2O5 concentration of 0.05 mol% for the electrical properties (alpha = 44 and E-B = 6150 V cm(-1)). (C) 2001 Elsevier B.V. Ltd. All rights reserved.

Second-order statistics for diversity-combining, techniques in Nakagami-fading channels

Exact and closed-form expressions for the level crossing rate and average fade duration are presented for the M branch pure selection combining (PSC), equal gain combining (EGC), and maximal ratio combining (MRC) techniques, assuming independent branches in a Nakagami environment. The analytical results are thoroughly validated by reducing the general case to some special cases, for which the solutions are known, and by means of simulation for the more general case. The model developed here is general and can be easily applied to other fading statistics (e.g., Rice).

Influence of simultaneous addition of MnO2 and CoO on properties of SnO2-based ceramics

This paper reports on a study of the: effect of replacing CoO by MnO2 on the sintering and electrical propel-ties of the 98.95% SnO2 + (1 - x)% CoO + x% MnO2 + 0.05% Ta2O5 system. All the samples were compacted into pellets and sintered at 1300 degrees C for 1 h, when they reached densities of about 98% of the theoretical density. An X-ray diffraction (XRD) analysis showed no other detectable phases other than SnO2. Current-voltage characterization indicated varistor behavior in the systems. The non-linear coefficient (alpha) and breakdown electric field (Eb) increased as the amount of MnO2 was increased. The results are explained in terms of an electric barrier modification, due to the presence of adsorbed negative oxygen species at the grain boundary inter face. (C) 2000 Elsevier B.V. B.V. All rights reserved.

Expressão gênica das adesinas e fatores de virulência da fase miceliar e leveduriforme do complexo paracoccidioides e de sua interação com células epiteliais e fagócitos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Caracterização do perfil de atividade física na vida diária de pacientes portadores de DPOC do Brasil e comparação com pacientes da Áustria

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da atividade apoptótica de substância pura isolada de Cryptocarya mandioccanna em células de carcinoma cervical imortalizadas pelo papilomavirus humano (HPV)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Desenvolvimento de sistemas líquido-cristalinos multifuncionais contendo nanopartículas de TiO2 para proteção solar e liberação controlada de terpinem-4-ol

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

Evolução dos marcadores diagnósticos e prognósticos de pacientes com DPOC no período de três anos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)