Inhibition of thimet oligopeptidase by siRNA alters specific intracellular peptides and potentiates isoproterenol signal transduction

Mammalian cells have a large number of intracellular peptides that are generated by extralysosomal proteases. In this study, the enzymatic activity of thimet oligopeptidase (EP24.15) was inhibited in human embryonic kidney (HEK) 293 cells using a specific siRNA sequence. The semi-quantitative intracellular peptidome analyses of siRNA-transfected HEK293 cells shows that the levels of specific intracellular peptides are either increased or decreased upon EP24.15 inhibition. Decreased expression of EP24.15 was sufficient to potentiate luciferase gene reporter activation by isoproterenol (1-10 mu M). The protein kinase A inhibitor KT5720 (1 mu M) reduced the positive effect of the EP24.15 siRNA on isoproterenol signaling. Thus, EP24.15 inhibition by siRNA modulates the levels of specific intracellular peptides and isoproterenol signal transduction. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

An extension of the invariance principle for dwell-time switched nonlinear systems

In this paper, we propose an extension of the invariance principle for nonlinear switched systems under dwell-time switched solutions. This extension allows the derivative of an auxiliary function V, also called a Lyapunov-like function, along the solutions of the switched system to be positive on some sets. The results of this paper are useful to estimate attractors of nonlinear switched systems and corresponding basins of attraction. Uniform estimates of attractors and basin of attractions with respect to time-invariant uncertain parameters are also obtained. Results for a common Lyapunov-like function and multiple Lyapunov-like functions are given. Illustrative examples show the potential of the theoretical results in providing information on the asymptotic behavior of nonlinear dynamical switched systems. (C) 2012 Elsevier B.V. All rights reserved.

Post-translational modification of the RhoGTPase activating protein 21, ARHGAP21, by SUMO2/3

ARHGAP21 is a 217 kDa RhoGAP protein shown to modulate cell migration through the control of Cdc42 and FAK activities. In the present work a 250 kDa-ARHGAP21 was identified by mass spectrometry. This modified form is differentially expressed among cell lines and human primary cells. Co-immunoprecipitations and in vitro SUMOylation confirmed ARHGAP21 specific modification by SUMO2/3 and mapped the SUMOylation site to ARHGAP21 lysine K1443. Immunofluorescence staining revealed that ARHGAP21 co-localizes with SUMO2/3 in the cytoplasm and membrane compartments. Interestingly, our results suggest that ARHGAP21 SUMOylation may be related to cell proliferation. Therefore, SUMOylation of ARHGAP21 may represent a way of guiding its function. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Prevalence of feline leukemia virus infection in domestic cats in Rio de Janeiro

Peripheral blood smears of 1094 domestic cats were collected and tested by indirect immunofluorescence antibody assay for p27 antigen in cells to study the prevalence and risk factors for feline leukemia virus (FeLV) in the state of Rio de Janeiro. Sex, age, breed, outdoor access, neutering status, type of habitation (household, shelter, veterinary clinics and other places), number of household cats and clinical signs were registered on a form. Among the tested samples, 11.52% were positive. Risk factors for FeLV infection included outdoor access, age range between 1 and 5 years old, and cohabitation with numerous cats.

Application of tetra-isopalmitoyl ascorbic acid in cosmetic formulations: Stability studies and in vivo efficacy

Liposoluble vitamin C derivatives, such as tetra-isopalmitoyl ascorbic acid (IPAA), are often used in dermocosmetic products due to their higher stability than vitamin C free form as well as its proposed effects in skin; however, there are no studies analyzing IPAA stability or its in vivo effects when present in dermocosmetic formulations. Thus, this study aimed to evaluate chemical stability and pre-clinical and clinical efficacy of dermocosmetic formulations containing IPAA in skin hydration and microrelief. Chemical stability of the formulations added with 1% IPAA was evaluated by heat stress during 35 days by HPLC. For pre-clinical evaluation, experimental formulations were topically applied on hairless skin mice during 5 days and animal skins were analyzed by non-invasive biophysic techniques (water content of stratum corneum, TEWL, viscoelasticity, and microrelief) and by histopathological studies. For clinical efficacy tests, the formulations were topically applied to the forearm and face of human volunteers, and 3 h and 15 days after applications, the skins were evaluated by the same non-invasive techniques mentioned before. Results showed that formulations containing IPAA had medium stability and had pronounced moisturizing effects on stratum corneum and on viable epidermis. These formulations also improved skin microrelief especially in relation to skin smoothness and roughness. (C) 2012 Elsevier B.V. All rights reserved.

Percepção do médico sobre pagamento por desempenho no gerenciamento de doenças cardiovasculares: o caso de uma operadora de plano de saúde

Desde os anos 50, os fatores de risco para as doenças cardiovasculares passaram a ser valorizados. O gerenciamento de doenças cardiovasculares (PGC) busca a construção da autonomia e melhoria da qualidade de vida dos pacientes. Em alguns países, para alcançar esses objetivos, tem sido apontada a utilização de programas de pagamento por desempenho (PPP) aos médicos como um dos elementos de melhoria nos processos e nos resultados dos pacientes e na condição de remuneração. O objetivo deste estudo é analisar o ponto de vista dos médicos sobre a implantação dos pagamentos por desempenho vinculados ao PGC em uma operadora de plano de saúde. Trata-se de investigação de caráter qualitativo, do tipo estudo de caso, apresentando entrevistas semiestruturadas com médicos participantes ou não do PGC, em setembro de 2009, tendo como referência as ações implantadas em 2008. Foram entrevistados 23 médicos (14 homens e 09 mulheres). Como resultado foi observado que o incentivo financeiro é reconhecido pelos médicos como importante, mas não determinante da inclusão de pacientes no PGC. O principal motivo apresentado foi a organização do cuidado, no qual o paciente é mais bem acompanhado e controlado, e o trabalho médico, avaliado segundo parâmetros preestabelecidos. O PGC e o PPP têm potencial de transformação do cuidado em saúde. O trabalho multidisciplinar e a maior produtividade nos atendimentos no consultório foram os principais efeitos positivos identificados. Outros estudos são necessários para acompanhar a evolução e os efeitos do pagamento por desempenho no trabalho médico.