Characterization of hepatic fatty acids using magnetic resonance spectroscopy for the assessment of treatment response to metformin in an eNOS-/- mouse model of metabolic nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. Liver biopsy remains the gold standard for diagnosis and staging of disease. There is a clinical need for noninvasive diagnostic tools for risk stratification, follow-up, and monitoring treatment response that are currently lacking, as well as preclinical models that recapitulate the etiology of the human condition. We have characterized the progression of NAFLD in eNOS-/- mice fed a high fat diet (HFD) using noninvasive Dixon-based magnetic resonance imaging and single voxel STEAM spectroscopy-based protocols to measure liver fat fraction at 3 T. After 8 weeks of diet intervention, eNOS-/- mice exhibited significant accumulation of intra-abdominal and liver fat compared with control mice. Liver fat fraction measured by 1 H-MRS in vivo showed a good correlation with the NAFLD activity score measured by histology. Treatment of HFD-fed NOS3-/- mice with metformin showed significantly reduced liver fat fraction and altered hepatic lipidomic profile compared with untreated mice. Our results show the potential of in vivo liver MRI and 1 H-MRS to noninvasively diagnose and stage the progression of NAFLD and to monitor treatment response in an eNOS-/- murine model that represents the classic NAFLD phenotype associated with metabolic syndrome.

Assessment of hepatic fatty acids during non-alcoholic steatohepatitis progression using magnetic resonance spectroscopy.

INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver abnormalities including steatosis, steatohepatitis, fibrosis, and cirrhosis. Liver biopsy remains the gold standard method to determine the disease stage in NAFLD but is an invasive and risky procedure. Studies have previously reported that changes in intrahepatic fatty acids (FA) composition are related to the progression of NAFLD, mainly in its early stages. The aim of this study was to characterize the liver FA composition in mice fed a Choline-deficient L-amino-defined (CDAA) diet at different stages of NAFLD using magnetic resonance spectroscopy (MRS). METHODS: We used in-vivo MRS to perform a longitudinal characterization of hepatic FA changes in NAFLD mice for 10 weeks. We validated our findings with ex-vivo MRS, gas chromatography-mass spectrometry and histology. RESULTS: In-vivo and ex-vivo results showed that livers from CDAA-fed mice exhibit a significant increase in liver FA content as well as a change in FA composition compared with control mice. After 4 weeks of CDAA diet, a decrease in polyunsaturated and an increase in monounsaturated FA were observed. These changes were associated with the appearance of early stages of steatohepatitis, confirmed by histology (NAFLD Activity Score (NAS) = 4.5). After 10 weeks of CDAA-diet, the liver FA composition remained stable while the NAS increased further to 6 showing a combination of early and late stages of steatohepatitis. CONCLUSION: Our results suggest that monitoring lipid composition in addition to total water/fat with MRS may yield additional insights that can be translated for non-invasive stratification of high-risk NAFLD patients.

Factors associated with occupational stress among nursing professionals in health services of medium complexity / Factores asociados al estrés laboral entre profesionales de enfermería en servicios de salud de mediana complejidad / Fatores associados ao estresse ocupacional entre profissionais de enfermagem em serviços de saúde de média complexidade

ABSTRACT Objective: To analyze the factors associated with occupational stress among nursing workers in health services of medium complexity. Methods: Epidemiological, cross-sectional, exploratory study. A randomly selected sample of 126 nursing professionals from medium complexity services in three cities in the state of Bahia (Santo Antônio de Jesus, Feira de Santana and Itabuna) was investigated. Data were collected in 2011 and 2012. The demand-control model proposed by Karasek was used to assess occupational stress. Simultaneous analysis of occupational stressors was performed using Poisson regression with robust variance. Results: The prevalence of occupational stress among nursing professionals was 77%. Occupational stress was associated with the professional category of nursing technician (p=0.01). Conclusion: The data indicates a concerning situation of exposure to occupational stressors, which requires coping strategies in order to protect the health of the worker.

RESUMEN Objetivo: analizar los factores asociados al estrés laboral entre trabajadores de enfermería de servicios de salud de mediana complejidad. Métodos: estudio epidemiológico, de diseño transversal y exploratorio. Se investigó una muestra de 126 profesionales de enfermería en tres municipios de Bahía. Los datos se recogieron durante los años 2011 y 2012. Para evaluar el estrés laboral, se utilizó el modelo demanda-control propuesto por Karasek. El análisis simultáneo de los factores laborales estresores se llevó a cabo mediante la regresión de Poisson con variancia robusta. Resultados: La prevalencia del estrés laboral entre profesionales de enfermería era del 77%. Dicho estrés estaba asociado a la categoría profesional de técnico/a de enfermería (p=0,01). Conclusión: Los datos demuestran la existencia de una situación preocupante en ese grupo, con exposición a estresores laborales, haciéndose necesario la adopción de estrategias de enfrentamiento a fin de garantizar una protección integral para la salud de los trabajadores.

RESUMO Objetivo: Analisar os fatores associados ao estresse ocupacional entre trabalhadores de enfermagem dos serviços de saúde de média complexidade. Métodos: Estudo epidemiológico, transversal, exploratório. Investigou-se amostra, aleatoriamente selecionada, de 126 profissionais de enfermagem dos serviços de média complexidade de três municípios na Bahia: Santo Antônio de Jesus, Feira de Santana e Itabuna. Os dados foram coletados nos anos de 2011 e 2012. Para avaliar o estresse ocupacional, utilizou-se o modelo demanda-controle, proposto por Karasek. A análise simultânea dos fatores ocupacionais estressores foi feita com emprego de regressão de Poisson com variância robusta. Resultados: A prevalência de estresse ocupacional entre profissionais de enfermagem foi de 77%. Estresse ocupacional associou-se à categoria profissional de técnico/a de enfermagem (p=0,01). Conclusão: Os dados evidenciam situação preocupante de exposição desse grupo a estressores ocupacionais, sendo necessária a adoção de estratégias de enfrentamento a fim de garantir proteção integral à saúde do/a trabalhador/a.

Assessment of Pradosia huberi effects on the reproductive system of male rats.

Pradosia huberi is a species found in the Amazon region and used as an antiulcerogenic and gastroprotective agent; however, phytochemical analysis has revealed the presence of compounds with potential toxic effects on the reproductive system. For the evaluation of the toxicity of P. huberi on male fertility, male Wistar rats were divided into four groups: one control (distilled water p.o.) and three treated (hydroalcoholic extract of the stem bark of P. Huberi (PH-HAE) at doses of 1.22, 6.1, and 30.5 mg/kg p.o.) once daily, for 63 days. In the last week of treatment (from the 57th to the 63rd day), the rats were mated with untreated virgin females (n = 30/group) and were killed on day 64. To investigate the toxic potential of PH-HAE on the reproductive system of rats the following parameters were evaluated: sperm production, genotoxicity, and general development. The production of gametes and their morphology did not differ between control and treated groups. Treatment with PH-HAE did not result in fewer vaginal plugs formed, indicating that the ability to mate was not impaired, but caused an increase of 14.3 and 10.8% in the preimplantation loss index, a reduction of 14.3 and 10.8% in the implantation index, and a reduction of 5.6 and 8.2% in the postimplantation loss index of female rats mated with rats treated with 6.1 and 30.5 mg/kg, respectively, indicating a possible toxic action of PH-HAE on the reproductive system of rats.