Metformin Treatment Modulates The Tumour-induced Wasting Effects In Muscle Protein Metabolism Minimising The Cachexia In Tumour-bearing Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Cancer-cachexia state frequently induces both fat and protein wasting, leading to death. In this way, the knowledge of the mechanism of drugs and their side effects can be a new feature to treat and to have success, contributing to a better life quality for these patients. Metformin is an oral drug used in type 2 diabetes mellitus, showing inhibitory effect on proliferation in some neoplastic cells. For this reason, we evaluated its modulatory effect on Walker-256 tumour evolution and also on protein metabolism in gastrocnemius muscle and body composition. Methods: Wistar rats received or not tumour implant and metformin treatment and were distributed into four groups, as followed: control (C), Walker 256 tumour-bearing (W), metformin-treated (M) and tumour-bearing treated with metformin (WM). Animals were weighed three times a week, and after cachexia state has been detected, the rats were euthanised and muscle and tumour excised and analysed by biochemical and molecular assays. Results: Tumour growth promoted some deleterious effects on chemical body composition, increasing water and decreasing fat percentage, and reducing lean body mass. In muscle tissue, tumour led to a decreased protein synthesis and an increased proteolysis, showing the higher activity of the ubiquitin-proteasome pathway. On the other hand, the metformin treatment likely minimised the tumour-induced wasting state; in this way, this treatment ameliorated chemical body composition, reduced the higher activities of proteolytic enzymes and decreased the protein waste. Conclusion: Metformin treatment not only decreases the tumour growth but also improves the protein metabolism in gastrocnemius muscle in tumour-bearing rats.16Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP [2010/00209-9, 2013/16115-1, 2014/13334-7]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPq [304604/2010-0, 302863/2013-3]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP, Sao Paulo, Brazil [2008/07737-0]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Human T Cell and Antibody-Mediated Responses to the Mycobacterium tuberculosis Recombinant 85A, 85B, and ESAT-6 Antigens

Tuberculosis remains a major health problem throughout the world causing large number of deaths. Effective disease control and eradication programs require the identification of major antigens recognized by the protective responses against M. tuberculosis. In this study, we have investigated humoral and cellular immune responses to M. tuberculosis-specific Ag85A, Ag85B, and ESAT-6 antigens in Brazilian patients with pulmonary (P, n = 13) or extrapulmonary (EP, n = 12) tuberculosis, patients undergoing chemotherapy (PT, n = 23), and noninfected healthy individuals (NI, n = 7). Compared to NI, we observed increased levels of IgG1 responses to Ag85B and ESAT-6 in P and PT groups. Regarding cellular immunity, Ag85A and ESAT-6 were able to discriminate P, PT, and EP patients from healthy individuals by IFN-γ production and P and PT groups from EP individuals by production of TNF-α. In summary, these findings demonstrate the ability of Ag85A, Ag85B, and ESAT-6 to differentiate TB patients from controls by IgG1, IFN-γ and TNF-α production

Developmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase

The xenotopic expression of the alternative oxidase AOX from the tunicate Ciona intestinalis in diverse models of human disease partially alleviates the phenotypic effects of mitochondrial respiratory chain defects. AOX is a non-proton pumping, mitochondrial inner membrane-bound, single-subunit enzyme that can bypass electron transport through the cytochrome segment, providing an additional site for ubiquinone reoxidation and oxygen reduction upon respiratory chain overload. We set out to investigate whether AOX expression in Drosophila could counteract the effects of mitochondrial DNA (mtDNA) replication defects caused by disturbances in the mtDNA helicase or DNA polymerase gamma. We observed that the developmental arrest imposed by either the expression of mutant forms of these enzymes or their knockdown was not rescued by AOX. Considering also the inability of AOX to ameliorate the phenotype of tko(25t), a fly mutant with mitochondrial translation deficiency, we infer that this alternative enzyme may not be applicable to cases of mitochondrial gene expression defects. Finding the limitations of AOX applicability will help establish the parameters for the future putative use of this enzyme in gene therapies for human mitochondrial diseases.Peer reviewe

Description of hospital pharmacy management practice

Health institutions, particularly hospitals, are characterized as complex structures that need managers with a global view of the institution and its relations with the external environment. The hospital pharmacy is a strategic unit, which cooperates with the institutional management and integrates the multiprofessional team in the process related to the acquisition, provision and control of essential inputs for the inpatient care process. The objective in this study is to demonstrate the applicability, in the context of hospital-based health, of a performance measuring system at the pharmacy. Method: A descriptive and longitudinal study was undertaken on the evolution of the key indicator Absence Rate of Standardized Drugs in inpatient care between March 2004 and December 2013. This indicator was employed to monitor the impact of changes the Pharmacy Division has been implementing, as the first step of the pharmaceutical care cycle in the model of the process-based managed approach at a public university hospital. Qualitative data collection methods were used, including observation and documentary analysis, as well as quantitative data collection. Results: After the application of the model, one point of change in the key performance indicator was detected in the tenth month, when the process-based management model was implemented at the pharmacy. Conclusions: The process-based management approach was effective for the hospital pharmacy. The premise adopted is that the administrative changes (interferences), focused on the improvement of the processes and the selection and monitoring of indicators, influence the processes, reducing the variability and improving the qualityAs instituições de saúde, especialmente hospitais, são caracterizadas como estruturas complexas que precisam de administradores com uma visão global da instituição e de suas relações com o ambiente externo. A farmácia hospitalar é uma unidade estratégica, que colabora com a administração institucional e integra a equipe multiprofissional no processo que tange a aquisição, provisão e controle de insumos essenciais para o processo do atendimento do paciente internado. Este estudo tem como objetivo demonstrar a aplicabilidade, no contexto da saúde hospitalar, de um sistema de medição de desempenho da farmácia. Método: Trata-se de um estudo descritivo, longitudinal, sobre a evolução do indicador chave Taxa de Falta de Medicamentos Padronizados na assistência do paciente internado, no período de março de 2004 a dezembro de 2013. Esse indicador foi empregado para monitoramento do impacto de mudanças que a Divisão de Farmácia vem implementando, como primeira etapa do ciclo de assistência farmacêutica dentro do modelo da abordagem de gestão por processos, em um hospital público universitário. Foram usados métodos de coleta de dados qualitativos, incluindo a observação e análise documental, bem como coleta de dados quantitativos. Resultados: Após a aplicação do modelo, um ponto de mudança no indicador chave de desempenho, foi detectado no 10º mês, quando o modelo de gestão baseado em processo foi implementado na farmácia. Conclusões: A abordagem de gestão baseada em processos foi eficaz para a farmácia hospitalar. A premissa adotada é que as mudanças administrativas (interferências), com foco na melhoria dos processos e seleção e acompanhamento de indicadores, têm influencia sobre os processos, reduzindo a variabilidade e melhoria da qualidad

Metabolic syndrome in patients with chronic hepatitis C virus genotype 1 infection who do not have obesity or type 2 diabetes

OBJECTIVE: The individual components of metabolic syndrome may be independent predictors of mortality in patients with liver disease. We aimed to evaluate the prevalence of metabolic syndrome and its related components in hepatitis C virus-infected patients who are not obese and do not have type 2 diabetes. METHODS: This cross-sectional study included 125 patients infected with hepatitis C virus genotype 1. Metabolic syndrome was defined according to the International Diabetes Federation. Anthropometric data were measured according to standardized procedures. Bioimpedance analysis was performed on all patients. RESULTS: Metabolic syndrome was diagnosed in 21.6&#37; of patients. Of the subjects with metabolic syndrome, 59.3&#37; had hypertension, 77.8&#37; had insulin resistance, 85.2&#37; were overweight, 48.1&#37; had a high waist circumference, 85.2&#37; had an increased body fat percentage, and 92.3&#37; had an elevated waist:hip ratio. In the bivariate analysis, female sex (OR 2.58; 95&#37; CI: 1.09-6.25), elevated gamma-glutamyl transferase (&#947;GT) (OR 2.63; 95&#37; CI: 1.04-7.29), elevated fasting glucose (OR 8.05; 95&#37; CI: 3.17-21.32), low HDL cholesterol (OR 2.80; 95&#37; CI: 1.07-7.16), hypertriglyceridemia (OR 7.91; 95&#37; CI: 2.88-22.71), elevated waist circumference (OR 10.33; 95&#37; CI: 3.72-30.67), overweight (OR 11.33; 95&#37; CI: 3.97-41.07), and increased body fat percentage (OR 8.34; 95&#37; CI: 2.94-30.08) were independent determinants of metabolic syndrome. Using the final multivariate regression model, similar results were observed for abdominal fat (OR 9.98; 95&#37; CI: 2.63-44.41) and total body fat percentage (OR 8.73; 95&#37; CI: 2.33-42.34). However, metabolic syndrome risk was also high for those with blood glucose >5.55 mmol/L or HDL cholesterol <0.9 mmol/L (OR 16.69; 95&#37; CI: 4.64-76.35; OR 7.23; 95&#37; CI: 1.86-32.63, respectively). CONCLUSION: Metabolic syndrome is highly prevalent among hepatitis C virus-infected patients without type 2 diabetes or obesity. Metabolic syndrome was significantly associated with hypertension, insulin resistance, increased abdominal fat, and overweight

Oxygen Gas Phase Abundance Revisited

We present new measurements of the interstellar gas-phase oxygen abundance along the sight lines towards 19 early-type galactic stars at an average distance of 2.6 kpc. We derive O {\small I} column densities from {\it HST}/STIS observations of the weak 1355 \AA intersystem transition. We derive total hydrogen column densities [N(H {\small I})+2N(H$_2$)] using {\it HST}/STIS observations of \lya and {\it FUSE} observations of molecular hydrogen. The molecular hydrogen content of these sight lines ranges from f(H$_2$) = 2N(H$_2$)/[N(H {\small I})+2N(H$_2$)] = 0.03 to 0.47. The average $$ of 6.3$\times10^{21}$ cm$^{-2}$ mag$^{-1}$ with a standard deviation of 15% is consistent with previous surveys. The mean oxygen abundance along these sight lines, which probe a wide range of galactic environments in the distant ISM, is 10$^6$ \oh = $408 \pm 13$ (1 $\sigma$ in the mean). %$({\rm O/H})_{gas} = 408 \pm 14$(1 $\sigma$). We see no evidence for decreasing gas-phase oxygen abundance with increasing molecular hydrogen fraction and the relative constancy of \oh suggests that the component of dust containing the oxygen is not readily destroyed. We estimate that, if 60% of the dust grains are resilient against destruction by shocks, the distant interstellar total oxygen abundance can be reconciliated with the solar value derived from the most recent measurements %by Holweger and by Allende Prieto, Lambert & Asplund: of 10$^6$ \oh$_\odot$ = 517 $\pm$ 58 (1 $\sigma$). We note that the smaller oxygen abundances derived for the interstellar gas within 500 pc %by Meyer, Cardelli & Jura or from nearby B star surveys are consistent with a local elemental deficit.Comment: 9 figures, 37 page

The youngest massive protostars in the Large Magellanic Cloud

We demonstrate the unique capabilities of Herschel to study very young luminous extragalactic young stellar objects (YSOs) by analyzing a central strip of the Large Magellanic Cloud obtained through the HERITAGE Science Demonstration Program. We combine PACS 100 and 160, and SPIRE 250, 350, and 500 microns photometry with 2MASS (1.25-2.17 microns) and Spitzer IRAC and MIPS (3.6-70 microns) to construct complete spectral energy distributions (SEDs) of compact sources. From these, we identify 207 candidate embedded YSOs in the observed region, ~40% never-before identified. We discuss their position in far-infrared color-magnitude space, comparing with previously studied, spectroscopically confirmed YSOs and maser emission. All have red colors indicating massive cool envelopes and great youth. We analyze four example YSOs, determining their physical properties by fitting their SEDs with radiative transfer models. Fitting full SEDs including the Herschel data requires us to increase the size and mass of envelopes included in the models. This implies higher accretion rates (greater than or equal to 0.0001 M_sun/yr), in agreement with previous outflow studies of high-mass protostars. Our results show that Herschel provides reliable longwave SEDs of large samples of high-mass YSOs; discovers the youngest YSOs whose SEDs peak in Herschel bands; and constrains the physical properties and evolutionary stages of YSOs more precisely than was previously possible.Comment: Main text: 4 pages, 3 figures, 1 table; Online material: 3 figures, 1 table; to appear in the A&A Herschel Special Issu

Processo de transferência de tecnologia da universidade para a indústria: estudo de caso envolvendo a conversão de glicerol

Currently, public policy has encouraged innovation in universities and also transference of technology to the industry. Another important stage to be considered would be the registration or filing of a patent and the economical viability study. Government programs, such as the innovation incentive program, among others, should facilitate popularization and promote interest by industry. In this work we described the steps, from the conception of the idea to the scale up going through its interest by the industry. The case study is about the glycerol conversion utilizing modified niobia as catalysts

Monolithic porous carbon materials prepared from polyurethane foam templates

Monolithic carbon foams with hierarchical porosity were prepared from polyurethane templates and resol precursors. Mesoporosity was achieved through the use of soft templating with surfactant Pluronic F127, and macroporosity from the polyurethane foams was retained. Conditions to obtain high porosity materials were optimized. The best materials have high specific surface areas (380 and 582 m(2) g(-1), respectively) and high electrical conductivity, which make them good candidates for supports in sensors. These materials showed an almost linear dependence between the potential and the pH of aqueous solutions

Tipología del miedo al delito y actitudes de aceptación de la violencia policial entre los habitantes de São Paulo, Brasil

Research suggests that the fear of crime affects people’s attitudes toward public security policies, favoring a preference for repressive or punitive actions towards what is considered a danger or a threat. Studies have pointed to a variety of possible individual and contextual factors that are antecedents of punitive attitudes. Fear of crime and punitive attitudes are the subject of public discourses that shape the criminal policies of many Western countries. Since emotions play a crucial role in criminal justice, criminologists seek to understand how these two concepts are related. In that sense, this study carried out an analysis of latent classes in a sample of inhabitants of the city of Sao Paulo (N=1806) to identify groups that describe the typologies of the association between the fear of crime and the favorable attitudes towards the violence of the police. The best model fit was of five latent classes. Among these groups, we find a profile in which there is a strong association between fear of crime and punitive attitude and another formed by those who report low fear of crime but have high levels of punitiveness. Furthermore, most of the people expressed not supporting police violence, despite showing fear of crime, so other factors could better explain the support for punitiveness that some groups present. We speculate few alternative explanations for these results in the discussion.Algunas investigaciones sugieren que el miedo al delito afecta a la actitud de las personas hacia las políticas de seguridad pública, favoreciendo una preferencia por acciones represivas o punitivas frente a lo que se considera un peligro o una amenaza. Los estudios han señalado una variedad de posibles factores individuales y contextuales que son antecedentes de actitudes punitivas. Además, el miedo al delito y las actitudes punitivas son el objeto de un discurso público que da forma a las políticas criminales de muchos países occidentales. Puesto que las emociones juegan un papel importante en la justicia penal, desde la criminología se han llevado a cabo investigaciones sobre cómo se interrelacionan ambos conceptos. En esta línea de investigación, este estudio realizó un análisis de clases latentes en una muestra de habitantes de la ciudad de São Paulo (N = 1806) para identificar agrupaciones que describen las tipologías de asociación entre miedo al delito y las actitudes favorables hacia la violencia policial. Los resultados mostraron la existencia de cinco perfiles. Entre estos, encontramos un perfil en el que hay una fuerte asociación entre el miedo al delito y la actitud punitiva y otro formado por aquellos que reportan bajo miedo al delito, pero presentan altos niveles de punitivismo. Además, la mayoría de las personas expresaron no apoyar la violencia policial, a pesar de tener miedo al delito, por lo que otros factores podrían explicar mejor el apoyo al punitivismo que presentan algunos grupos. En la discusión se ofrecen algunas explicaciones alternativas a estos resultados