RESUMO Contexto: Carcinoma hepatocelular (CHC) é o tipo mais comum de câncer de fígado. Os fatores de risco para CHC incluem infecção pelo vírus da hepatite C (VHC) e B (VHB), cirrose alcoólica e alterações genéticas que podem afetar diversas vias celulares. Objetivo: Este estudo teve como objetivo analisar a expressão gênica e proteica sérica de VEGF, AFP, CSTB, β-catenina e GPC3 em grupos com CHC, cirrose ou VHC e controles, e sua relação com o estadiamento clínico nos grupos CHC e cirrose, bem como sua valores de sensibilidade e especificidade. Métodos: Duzentos e trinta indivíduos foram distribuídos no Grupo 1 (G1) - 80 pacientes com CHC; Grupo 2 (G2) - 76 pacientes com cirrose de qualquer etiologia; Grupo 3 (G3) - 33 pacientes com VHC; Grupo 4 (G4 - Controles) - 41 indivíduos sem sinais clínicos ou bioquímicos de qualquer doença hepática. A expressão gênica foi analisada por qRT-PCR e as proteínas séricas foram realizadas pelo método ELISA. Resultados: Aumento da expressão de VEGF e AFP pode ser observado em pacientes BCLC estágio D em comparação com pacientes estágio B, e pacientes estágio C apresentaram maior expressão de CTNNB1, em comparação com pacientes estágio B (P<0,05). Para VEGF e GPC3, foi observado poder discriminatório entre pacientes com CHC e controles (AUC = 0,71; 0,82, respectivamente). O CSTB mostrou poder discriminatório na comparação entre pacientes com VHC e controles (AUC =0,74). Conclusão: O presente estudo confirma a sensibilidade do CSTB sérico no diagnóstico da hepatite C, e a expressão gênica de VEGF e GPC3 sérica conferem sensibilidade e especificidade para o diagnóstico de CHC.

ABSTRACT Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Risk factors for HCC include hepatitis C (HCV) and B (HBV) virus infection, alcoholic cirrhosis and genetic alterations that can affect several cellular pathways. Objective: This study purposed to analyze the gene and serum protein expression of vascular endothelial growth factor (VEGF), angiogenesis, alpha fetoprotein, cystatin B (CSTB), β-catenin and glypican-3 (GPC3) in groups with HCC, cirrhosis or HCV and controls, and their relation with clinical staging in the HCC and cirrhosis groups, as well its sensitivity and specificity values. Methods: A total of 230 individuals were distributed in Group 1 (G1) - 80 patients with HCC; Group 2 (G2) - 76 patients with cirrhosis due to any etiology; Group 3 (G3) - 33 patients with HCV; Group 4 (G4 - controls) - 41 individuals without clinical or biochemical signs of any liver disease. Gene expression was analyzed by qRT-PCR and serum proteins were performed using the ELISA method. Results: Increased VEGF and angiogenesis, alpha fetoprotein expression could be observed in BCLC stage-D patients compared to stage-B patients, and stage-C patients showed higher expression of β-catenin, compared to stage-B patients (P<0.05). For VEGF and GPC3, discriminatory power was observed between HCC patients and controls (AUC =0.71; 0.82, respectively). CSTB showed discriminatory power in the comparison between patients with HCV and controls (AUC =0.74). Conclusion The present study confirms the sensitivity of serum CSTB in the diagnosis of hepatitis C, and gene expression of VEGF and serum GPC3, confer both sensitivity and specificity for the diagnosis of HCC.

Abstract Introduction Schizophrenia is a complex psychiatric disorder that affects approximately twenty million people worldwide. Various factors have been associated with the physiopathology of this disease such as oxidative stress, which is an imbalance between pro-oxidant and antioxidant molecules. Objective This study evaluated the association between biomarkers of oxidative stress and response to pharmacological treatment among patients with schizophrenia in the context of their clinical information, demographic data, and lifestyle. Methods A total of 89 subjects were included, 26 of whom were treatment-responsive schizophrenia patients (Group 1), 27 treatment-resistant schizophrenia patients (Group 2), and 36 healthy controls (Group 3). All of the subjects completed a questionnaire to provide clinical and demographic data, and all provided peripheral blood samples. The oxidative stress markers analyzed using spectrophotometry were catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), total glutathione (GSH-t), malondialdehyde (MDA), and Trolox-equivalent antioxidant capacity (TEAC; p < 0.05). Results When all schizophrenia patients (G1 + G2) were compared to the control group, SOD levels were found to be lower among schizophrenia patients (p < 0.0001), while MDA and CAT levels were higher (p < 0.0001 and p = 0.0191, respectively). GPx, GSH-t, and TEAC levels were similar in all three groups (p > 0.05). Conclusion Lower SOD levels and higher MDA and CAT levels indicate oxidative damage in schizophrenia patients, regardless of their response to pharmacological treatment. Smoking is associated with oxidative stress, in addition, a family history of the disease was also found to be correlated with cases of schizophrenia, which reflects the relevance of genetics in disease development.

RESUMO Introdução Glioma, tumor cerebral maligno, é altamente agressivo e associado a mau prognóstico. Os objetivos deste estudo foram avaliar a associação de polimorfismos genéticos relacionados a angiogênese e apoptose em pacientes com glioma, bem como suas comorbidades, hábitos de vida, perfil clínico, sobrevida e resposta ao tratamento (temozolomida [TMZ] e radioterapia [RT]). Métodos 303 indivíduos foram genotipados por PCR em tempo real, e foram coletados dados clínicos, hábitos de vida e comorbidades. Admitiu-se nível de significância para valor p < 0,05. Resultados Tabagismo, elitismo, hipertensão arterial sistêmica, diabetes mellitus e índice de massa corporal prevaleceram entre os pacientes, comprados aos controles (p < 0,05). O genótipo heterozigoto rs1468727 (T/C) e homozigoto rs2010963 (G/G) (p > 0,05) foram observados em ambos os grupos. Tabagismo, elitismo, hipertensão arterial sistêmica, diabetes mellitus e índice de massa corporal apresentaram fatores de risco independentes para a doença (p < 0.0001, p = 0.0069, p = 0.0394, respectivamente). Os pacientes com gliomas de baixo grau apresentaram sobrevida de 80,0 ± 1,7% em três anos. Para a combinação de RT e TMZ, a sobrevida foi de 78,7±7,6% em 20 meses, em comparação com TMZ (21,9 ± 5,1%, p = 0,8711). Conclusões As variantes genéticas não estiveram associadas aos gliomas. Hábitos de vida e comorbidades específicas destacaram-se como fatores de risco independentes para a doença. O tratamento com TMZ + RT mostrou aumento na sobrevida dos pacientes.

ABSTRACT Background Glioma, the most common primary malignant brain tumor in adults, is highly aggressive and associated with a poor prognosis. The objectives of this study were to evaluate the association of genetic polymorphisms related to angiogenesis and apoptosis with gliomas, as well as comorbidities, lifestyle, clinical profile, survival and response to treatment (temozolomide [TMZ] and radiotherapy [RT]) in patients with the disease. Methods In a total of 303 individuals, genotypes were performed by real-time PCR, and clinical data, lifestyle and comorbidities were obtained from medical records and questionnaires. The significance level was set at 5%. Results Smoking, alcohol consumption, systemic arterial hypertension, diabetes mellitus and body mass index prevailed among patients, compared to controls (p < 0.05). The heterozygous genotype rs1468727 (T/C) and the homozygous genotype rs2010963 (G/G) (p > 0.05) were observed in both groups. Lifestyle and comorbidities showed independent risk factors for the disease (p < 0.0001, p = 0.0069, p = 0.0394, respectively). Patients with low-grade gliomas had a survival rate of 80.0 ± 1.7% in three years. For the combination of TMZ+RT, survival was 78.7 ± 7.6% in 20 months, compared to TMZ only (21.9 ± 5.1%, p = 0.8711). Conclusions Genetic variants were not associated with gliomas. Specific lifestyle habits and comorbidities stood out as independent risk factors for the disease. Low-grade gliomas showed an increase in patient survival with TMZ+RT treatment.

Resumo Objetivo: A proteína interleucina 8 promove respostas inflamatórias, o que inclui sua atuação nas vias aéreas. A presença de variantes no gene da interleucina 8 causa respostas inflamatórias alteradas e possivelmente respostas variadas ao uso de broncodilatadores inalatórios. Assim, este estudo analisou as variantes da interleucina 8 (rs4073, rs2227306, rs2227307) e sua associação à resposta a broncodilatadores inalatórios em pacientes com fibrose cística. Métodos: Foi feita análise das variantes genéticas da interleucina 8 por restriction fragment length polymorphism da reação em cadeia da polimerase. A associação entre os marcadores da espirometria e a resposta a broncodilatadores inalatórios foi feita pelos testes de Mann-Whitney e Kruskal-Wallis. A análise incluiu todos os pacientes com fibrose cística e posteriormente pacientes com duas mutações no gene cystic fibrosis transmembrane conductance regulator pertencentes às Classes I a II. Resultados: Este estudo incluiu 186 pacientes com fibrose cística. Não houve associação da variante rs2227307 à resposta a broncodilatadores inalatórios. A variante rs2227306 foi associada a FEF50% no grupo dominante e no grupo com duas mutações identificadas no gene cystic fibrosis transmembrane conductance regulator. A variante rs4073 foi associada a marcadores da espirometria em quatro modelos genéticos: codominante (FEF25-75% e FEF75%), dominante (VEF1, FEF50%, FEF75% e FEF25-75%), recessivo (FEF75% e FEF25-75%) e overdominante (VEF1/CVF). Conclusões: Este estudo destaca, principalmente, a importância da variante rs4073 do gene da interleucina 8, na resposta a broncodilatadores inalatórios, concomitantemente ao genótipo das mutações no gene cystic fibrosis transmembrane conductance regulator.

Abstract Objective: Interleukin 8 protein promotes inflammatory responses, even in airways. The presence of interleukin 8 gene variants causes altered inflammatory responses and possibly varied responses to inhaled bronchodilators. Thus, this study analyzed the interleukin 8 variants (rs4073, rs2227306, and rs2227307) and their association with the response to inhaled bronchodilators in cystic fibrosis patients. Methods: Analysis of interleukin 8 gene variants was performed by restriction fragment length polymorphism of polymerase chain reaction. The association between spirometry markers and the response to inhaled bronchodilators was evaluated by Mann-Whitney and Kruskal-Wallis tests. The analysis included all cystic fibrosis patients, and subsequently patients with two mutations in the cystic fibrosis transmembrane conductance regulator gene belonging to classes I to III. Results: This study included 186 cystic fibrosis patients. There was no association of the rs2227307 variant with the response to inhaled bronchodilators. The rs2227306 variant was associated with FEF50% in the dominant group and in the group with two identified mutations in the cystic fibrosis transmembrane conductance regulator gene. The rs4073 variant was associated with spirometry markers in four genetic models: co-dominant (FEF25-75% and FEF75%), dominant (FEV1, FEF50%, FEF75%, and FEF25-75%), recessive (FEF75% and FEF25-75%), and over-dominant (FEV1/FVC). Conclusions: This study highlighted the importance of the rs4073 variant of the interleukin 8 gene, regarding response to inhaled bronchodilators, and of the assessment of mutations in the cystic fibrosis transmembrane conductance regulator gene.

RESUMOObjetivo:Avaliar a associação entre o polimorfismo VEGF-C936T, níveis séricos de VEGF (vascular endothelial growth factor), hábitos de vida e antecedentes pessoais em pacientes com degeneração macular relacionada à idade (DRMI).Métodos:Foram estudados 183 indivíduos: 88 pacientes com degeneração macular relacionada à idade, em tratamento clínico e medicamentoso (Grupo Estudo - GE) e 95 indivíduos sem sinais clínicos da doença (Grupo Controle - GC). O polimorfismo VEGF-C936T e os níveis séricos de VEGF foram analisados por PCR/RFLP e ELISA, respectivamente. Admitiu-se nível de significância para P<0.05.Resultados:O genótipo homozigoto selvagem (CC) prevaleceu em ambos os grupos (P=0,934), assim como o alelo C (P=0,938). Os níveis séricos de VEGF, analisados em 57% de SG e em 31% de CG, apresentaram valores semelhantes entre pacientes e controles (GE=307,9 ± 223,6 pg/mL; GC=305,1 ± 212,3 pg/mL; P=0,955). Notou-se maior frequência de tabagismo (44%) e hipertensão arterial sistêmica (66%) em GE versus GC (25%; 48%; P=0,01; P=0,025, respectivamente). A distribuição de etilismo e dislipidemia foi semelhante entre os grupos (P>0,05).Conclusões:Em nosso estudo com pacientes brasileiros, o polimorfismo VEGF-C936T não se associa com degeneração macular relacionada à idade, por outro lado, tabagismo e HAS são potencialmente fatores de risco independentes para a doença, enquanto níveis de VEGF semelhantes em ambos os grupos podem refletir o sucesso do tratamento farmacológico.

ABSTRACTPurpose:To evaluate the association between the VEGF-C936T polymorphism and serum vascular endothelial growth factor (VEGF) levels, lifestyle, and demographic parameters in patients with age-related macular degeneration (AMD).Methods:A total of 183 individuals were enrolled in the present study, including 88 patients with AMD receiving clinical and pharmacological treatment (study group, SG) and 95 individuals without AMD as controls (control group, CG). The presence of the VEGF-C936T polymorphism and serum VEGF levels were determined using polymerase chain reaction/restriction fragment length polymorphism and enzyme-linked immunosorbent assay, respectively. Significance was set at P<0.05 for all statistical analyses.Results:The homozygous wild-type genotype (CC) and the C allele were predominant in both groups (P=0.934 and P=0.938, respectively). Serum VEGF levels (assessed in 57% and 31% of patients in the SG and CG, respectively) were comparable between groups (SG, 307.9 ± 223.6 pg/mL; CG, 305.1 ± 212.3 pg/mL; P=0.955). A significantly higher prevalence of smoking (44% vs 25%; P=0.01) and hypertension (66% vs 48%; P=0.025) was observed in the SG than in the CG. The distribution of alcohol consumption and dyslipidemia was similar between groups (P>0.05).Conclusions:In the present study group of Brazilian patients, the VEGF-C936T polymorphism was not found to be associated with age-related macular degeneration. However, smoking and systemic arterial hypertension (SAH) were found to be potential independent risk factors for the development of age-related macular degeneration. Comparable serum VEGF levels in both study groups may reflect the efficacy of pharmacological treatment of AMD.

The objective of this study was to analyze the effects of passive smoking, in soleus and gastrocnemius muscles associated with physical exercise by swimming during pregnancy and lactation of rats. Twenty-four rats were divided: GF (exposed to cigarette smoke), GC (control), GFN (underwent to the swimming program and exposed to cigarette smoke) and GN (underwent to the swimming program). On the first day of pregnancy procedure of exposure to cigarette smoke began, consisting in 30 minutes twice a day for six weeks. During the same period the swimming program began, which lasted 60 min every day untilthe 21st day of lactation. Soleus and gastrocnemius muscles, were obtained for histological, histochemical, morphometric analysis and fiber profiling. In histology, the groups GF and GFN showed infiltrations, necrotic and phagocytized fibers, centralized nuclei, splittings and coiling; in GN changes were observed due to exercise adaptations, infiltrations, sarcolemal lesion, polymorphic, atrophic and angular fibers. In the histochemical analysis of the groups GF and GFN there was enzymatic activity and amorphous formazan aggregates in subsarcolemmal positions, however in GN the same changes were found in lower frequency and intensity. In regard to the measureof the cross-sectionofmuscle fibers there weren't significant differences among the groups, as well as, in the frequency of types of fibers of the gastrocnemius. It is concluded that aerobic exercise is not enough to impede morphological and histochemical changes caused in an animal model of pregnant and lactating associated with smoking, and the stress not influence the types and size of muscle fibers.

EL objetivo fue analizar los efectos del tabaquismo pasivo sobre los músculos sóleo y gastrocnemio asociado con el entrenamiento corporal de natación durante la preñez y lactancia de ratas. Veinticuatro ratas se dividieron en grupos: GF (expuestos al humo de cigarrillo), GC (control), GFN (sometido al programa de natación y expuesto al humo del cigarrillo) y GN (sometido al programa de natación). El procedimiento de exposición al humo del cigarrillo comenzó primer día de preñez, durante 30 min dos veces al día por seis semanas. Durante el mismo período, comenzó el programa de natación, con una duración de 60 min todos los días hasta el día 21 de lactancia. Se extrajeron los músculos sóleo y gastrocnemio, y se realizó el análisis histológico, morfométrico histoquímico y de perfiles de fibra. En la histología, los grupos GF y GFN mostraron infiltraciones, fibras necróticas y fagocitadas, núcleos centralizados, divisiones y enrollamientos; en GN se observaron cambios debido a las adaptaciones de ejercicio tales como infiltraciones, lesión del sarcolema, y fibras polimórficas, atróficas y angulares. En el análisis histoquímico de los grupos GF y GFN hubo actividad enzimática y se formaron agregados amorfos en posiciones subsarcolemales; en el grupo GN se encontraron los mismos cambios en menor frecuencia e intensidad. No hubo diferencias en las medidas de las secciones transversales de las fibras musculares entre los grupos, así como en la frecuencia de los tipos de fibras del músculo gastrocnemio. Se concluye que el ejercicio aeróbico no es suficiente para impedir los cambios morfológicos e histoquímicos causados en un modelo animal de ratas preñadas en periodo de lactancia asociados con el tabaquismo, y el estrés no influye en el tipo y tamaño de las fibras musculares.

Objetivo: Este estudo teve como objetivo avaliar a associação de degeneração macular relacionada à idade (DMRI) com variantes de alipoproteína E (APOE) e perfil lipídico sérico, incluindo níveis séricos de colesterol total (TC) e frações de proteínas relacionadas a receptor de LDL (LDLc) e HDL colesterol (HDLc), e triglicérides (TG). Métodos: Realizouse genotipagem de APOE-HhaI em 134 pacientes (grupo de estudo SG) e 164 indivíduos sem a doença (grupo controle CG), na faixa etária entre 5089 anos. O perfil lipídico sérico foi analisado em um subgrupo de 30 indivíduos de ambos os grupos, pareados por idade e sexo. Admitiuse nível de significância para valorP<0,05. Resultados: APOE E3/E3 prevaleceu (SG=74,6%; CG=77,4%), sem diferença entre os grupos (P=0,667), o mesmo ocorreu para genótipos de risco (APOE /E2: SG=7,4%; CG=10,3%,P=0,624).Níveis séricos de TC, LDLc e TG mostraram medianas semelhantes entre SG (193,5; 116; 155 mg/dL, respectivamente) e CG (207,5; 120; 123,5 mg/dL respectivamente; P>0,05). Para HDLc notouse valor de mediana elevado em SG (53,3 mg/dL) versus CG (42,5 mg/dL; P=0,016), constatado também na análise de regressão logística, cuja razão HDLc/TC mostrou coeficiente 11,423 (P=0,014), confirmando acréscimo de HDLc em SG. A relação entre perfil lipídico sérico e genótipos de APOE mostrou semelhança entre os grupos (P>0,05). Conclusão: APOE-HhaI não se associa a DMRI, no entanto, o acréscimo no nível sérico de HDLc parece ter efeito protetor contra a doença, independente de variantes genéticas da apoE.

Purpose: This study aimed to evaluate the association of age-related macular degeneration (AMD) with apolipoprotein E (APOE) variants and serum lipid profiles, including levels and fractions of total serum cholesterol (TC), low-density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol (HDLc), and triglycerides (TG). Methods: Genotyping of APOE-HhaI was performed in 134 patients (study group, SG) and 164 individuals without AMD (control group, CG), aged 50-89 years. Lipid profiles were analyzed in a subgroup of 30 subjects of both groups, matched according to age and sex. The significance level was set at P<0.05. Results: APOE E3/E3 was more prevalent (SG=74.6%; CG=77.4%), with no difference between both groups (P=0.667). The same result was observed for risk genotypes (APOE E -/2: SG=7.4%; CG=10.3%, P=0.624). Serum levels of TC, LDLc, and TG revealed similar median values between SG (193.5, 116, and 155 mg/dL, respectively) and CG (207.5, 120, and 123.5 mg/dL, respectively; P >0.05). For HDLc, a higher median value was observed in SG (53.3 mg/dL) versus CG (42.5 mg/dL; P=0.016). Logistic regression analysis showed the same value, and the HDLc/TC ratio was -11.423 (P=0.014), as also confirmed by an increase in HDLc in SG. The association between lipid profiles and apolipoprotein E genotypes was similar in both groups (P>0.05). Conclusion: APOE-HhaI is not associated with AMD. However, an increase in serum HDLc level appears to exert a protective effect against the disease, irrespective of the genetic variants of apoE.

The present study was carried out to evaluate the effect of statins associated with physical exercise (PE) in liver cells in dyslipidemic rats through cariometry. The animals were divided into six groups: animals subjected to a hypercholesterolemic diet (HD), simvastatin, with (G1) and without (G2) physical exercise (PE); HD submitted (G3) or not (G4) to PE, and commercial food diet (F) with (G5) and without (G6) PE. Histological analysis of the liver was performed by staining the slides with hematoxylin and eosin. The cariometric study included measuring the major and minor diameters of the hepatocytes nuclei. The Shapiro-Wilk test was also performed. To determine the differences among the groups, the Kruskal-Wallis Test with Dunn's post-test were conducted. The significance level was set at 5%. No difference was found in the hepatocytes nuclei between G5 and G6. When these groups were related with G3 and G4, reduced nuclei were observed. There was no difference between G1 and G6. The comparison between G6 and G2 showed that the nuclei in G2 were smaller. No difference was detected between G5 and G1. Changes were observed in the nuclei shape in G2 in comparison to G1. Considering G2 and G3, a decrease in the size of nuclei was observed in G3. On the other hand, G2 showed changes in shape in the comparative analysis with G4. The size and shape of G1 nuclei were larger than G3 as well as changes in shape were observed when compared to G4. G4 showed smaller nuclei than G3. Therefore, F, associated or not with the practice of PE, does not alter the size and shape of the hepatocytes nuclei; HD combined with sedentarism influences changes in the morphometric parameters of hepatocytes; and the association of simvastatin and PE seems to protect the hepatocytes nuclei with regard to HD.

As estatinas são utilizadas no tratamento das dislipidemias, com grande tolerância; no entanto, vários efeitos colaterais podem surgir, destacando-se miopatia. A prática regular do exercício físico (EF) produz modificações favoráveis no perfil lipídico; entretanto, pode gerar lesões musculares. OBJETIVO: Avaliar o efeito da associação entre exercício físico e estatinas na função muscular, pela análise histológica, em modelo experimental animal com dislipidemia. MÉTODOS: Foram utilizados 80 ratos machos Wistar, distribuídos em oito grupos, incluindo animais submetidos à dieta hipercolesterolêmica (DH), sinvastatina com (G1) e sem (G2) EF; DH e fluvastatina, com (G3) e sem EF (G4); alimentados com ração comercial (RC) na presença (G5) e ausência de (G6) EF; DH submetidos (G7) ou não (G8) a EF. A DH foi administrada por 90 dias, as estatinas e prática de EF em esteira rolante por oito semanas. Os animais foram sacrificados, e o músculo sóleo retirado para análise histológica. Aplicaram-se os testes t de Student pareado e análise multivariada, com nível significante para p < 0,05. RESULTADOS: As principais alterações histológicas encontradas foram fibras de diferentes diâmetros, atróficas, em degeneração, splitting, edema, infiltrado inflamatório. Essas alterações foram observadas em 90% dos animais do grupo G1, 80% do G2, 70% do G3, 30% do G4, 40% do G5 e 30% do G7. Nos grupos G6 e G8 identificaram-se fibras musculares com morfologia preservada. CONCLUSÕES: Na avaliação histológica muscular, a associação entre fluvastatina, sinvastatina e exercício físico acarreta alterações morfológicas com predomínio no uso da sinvastatina, variando de grau leve a grave, no músculo sóleo de ratos, induzidos pelos inibidores da HMG-CoA redutase.

Statins are used in the treatment of dyslipidemias with great tolerance; however, several side effects can arise, mainly myopathies. Regular practice of physical exercises (PE) produces beneficial alteration in the lipid profile, but it can result in muscular lesions. OBJECTIVE: to evaluate the effect of the association between physical exercise and statins in the muscular function through histological analysis in an experimental animal model with dyslipidemia. METHODS: 80 male Wistar mice, distributed in 8 groups, namely: animals submitted to a hypercholesterolemic diet (HD), symvastatin with (G1) and without PE (G2) ; HD and fluvastatin with (G3) and without PE (G4); fed with commercial food (CR) in the presence (G5) and absence of PE (G6); HD submitted (G7) or not (G8) to PE were used. The HD was administered statins and PE practice on treadmill for 90 days for 8 weeks. The animals were sacrificed, and the soleus muscle was removed for histological analysis. Paired t-tests and multivariate analysis were applied with significance level of p<0.05. RESULTS: The most important histological alterations found were fibers with different diameters and atrophic, with degeneration, splitting, edema and inflammatory infiltrate. These alterations were observed in 90% of animals from G1; 80% from G2; 70% from G3; 30% from G4; 40% from G5 and 30% from G7. In the G6 and G8 groups muscular fibers with preserved morphology were identified. CONCLUSION: In the muscular histological evaluation, the association of fluvastatin, symvastatin and physical exercise results in morphological alterations with predominance with the use of simvastatin, varying from a light to a high level, in the soleus muscle of mice, induced by HMG-CoA reductase inhibitors.

Para que haja estruturação de um programa voltado ao controle e prevenção de agravos da asma, é necessário que se estabeleçam ações de regionalização, planejamento e gerenciamento. Hoje, as Portarias Ministeriais permitem que cada município trate suas necessidades com iniciativas locais, baseadas na busca dos indicadores de saúde em parceria com a universidade. Nesse contexto, torna-se factível a implantação de um modelo ideal por meio de demanda organizada por fluxo de atendimento e estrutura física, além da dispensação de medicamentos e capacitação profissional. Objetiva-se a descrição da situação atual modus operandi das Unidades Básicas de Saúde (UBSs) para captação, diagnóstico e seguimento do paciente com asma, assim como da situação atual quanto aos perfis profissional e setorial. Apresenta-se um modelo assistencial para captação, diagnóstico e seguimento do asmático na atenção primária. Trata-se de uma revisão bibliográfica baseada na literatura especializada, por meio de consulta a artigos científicos selecionados pelos bancos de dados SciELO e Bireme, a partir das fontes Medline e Lilacs. Foi criado um Comitê composto por membros que representam a Secretaria de Saúde, a universidade e as sociedades científicas para discussão e planificação.

To create a program structured for the control and prevention towards asthma worsening, it is necessary to settle down actions of regionalization, planning and management. Currently, the Ministerial orders allow each municipality district to cope their needs with local initiatives, based on the search of the health indicators with University partnerships. Taking into account this context, it is feasible the implantation of an effective model through organized demand of attendance flow and physical structure, besides the withdrawal of medications and professional training. To describe the modus operandi situation currently in the Primary Health Care Units regarding these patients' reception, diagnosis, and follow-up, as well as the current situation according to the professional profile and sector. To introduce an assistance model for reception, of these patients in these primary care units. This is a bibliographical review based on the specialized literature such as scientific papers selected through the search on the SciELO and Bireme databases, from Medline and Lilacs data sources. A Committee was set up by members from the Health and Service , the Medical School, and scientific societies for discussion and planning.

A influência do conhecimento de estudantes de medicina sobre o manejo com o fim da vida, considerando teorias éticas e aplicabilidade clínica, permanece controversa. Objetivamos investigar o conhecimento de estudantes de medicina sobre conceitos bioéticos a respeito dos tipos morais de morte (Eutanásia, Distanásia e Ortotanásia) e analisar a influência de suas experiências clínicas para praticá-los, em um hospital terciário do estado de São Paulo, Brasil. Nós entrevistamos 180 estudantes de medicina [distribuídos em Grupo 1 (G1) - estudantes do primeiro ao terceiro ano de graduação em medicina e Grupo 2 (G2) - estudantes do quarto ao sexto ano] para avaliar a influência do "curso de ética médica" em teorias éticas e prática clínica, utilizando um questionário fechado. O "curso de ética médica" não diferiu os grupos (P=0.704) sobre os conceitos bioéticos. Neologismos como Cacotanásia e Idiotanásia foram erroneamente considerados como conceitos bioéticos por 28% dos indivíduos. Além disso, 45.3% da amostra consideraram os profissionais de saúde inaptos ao manejo de pacientes terminais, principalmente G2 (29%) comparado a G1 (16.5%, P=0.031). O conceito de Eutanásia foi aceito por 41% da amostra, enquanto Ortotanásia por 98.2%. Dentre os estudantes de medicina que aceitaram maneiras para abreviar a vida (22.9%), 30.1% deles pertenciam a G1 enquanto somente 16.1% a G2 (P=0.049). Estudantes de medicina mostram desconhecimento sobre conceitos clássicos em Bioética. Além disso, consideram os profissionais de saúde inaptos ao manejo de pacientes terminais. O ideal ético considerando a "boa morte" reflete melhor aceitação dos estudantes de medicina pela Ortotanásia, sugerindo tendência em aplicá-la em sua futura prática clínica.

The influence of medical students' knowledge concerning end-of-life care, considering ethical theories and clinical practice, remains controversial. We aimed to investigate medical students' knowledge of bioethical concepts related to moral kinds of death (euthanasia, disthanasia, and orthothanasia) and to analyze the influence of their clinical experience on practicing such approaches in a tertiary hospital in the state of São Paulo, Brazil. We interviewed 180 medical students [distributed in Group 1 (G1) - first to third- year students, and Group 2 (G2) - fourth to sixth-year students] to evaluate the influence of the course on "medical ethics" on ethical theories and clinical practice, using a closed questionnaire. The course on "medical ethics" did not distinguish the groups (P=0.704) in relation to bioethical concepts. Neologisms such as "cacothanasia" and "idiothanasia" were incorrectly viewed as bioethical concepts by 28% of the interviewees. Moreover, 45.3% of the sample considered health care professionals incapable of managing terminally ill patients, especially G2 (29%) as compared to G1 (16.5%, P=0.031). The concept of euthanasia was accepted by 41% of sample, as compared to 98.2% for orthothanasia. Among medical students that accepted ways to abbreviate life (22.9%), 30.1% belonged to G1, and only 16.1% to G2 (P=0.049). These medical students were unfamiliar with common bioethical concepts. Moreover, they considered healthcare professionals incapable of managing terminally ill patients. The ethical ideal of the "good death" reflects better acceptance of orthothanasia by medical students, suggesting a tendency to apply it in their future clinical practice.

OBJETIVO: Avaliar se perfil lipídico (PL), apolipoproteína A-1 (apo A-I) e malondialdeído (MDA) têm relação com atividade física comparando os grupos: jogadores de futebol (FG) com indivíduos sedentários (CG) e seus familiares. SUJEITOS E MÉTODOS: Foram avaliados 20 indivíduos de FG e CG, além de 60 familiares de FG (RFG) e 57 de CG (RCG). RESULTADOS: FG mostrou menores níveis (média ± DP [mg/dL]) de colesterol total (119.5 ± 37.9), LDL colesterol (53.6 ± 30.3), e apo A-I (116.7 ± 11.9), e maiores níveis de HDL colesterol (HDLc) (49.7 ± 8.5) comparado ao RFG (148.3 ± 36.9, P = 0.02; 82.4 ± 37.7, P < 0.01; 124.6 ± 10.2, P = 0.03; e 42.7 ± 7.7, P < 0.01; respectivamente). Além disso, o FG mostrou níveis reduzidos de MDA (101.0 ± 77.0 [ng/mL]) comparado a CG (290.0 ± 341.0, P = 0.03) e RFG (209.9 ± 197.5, P = 0.04). CONCLUSÕES: Esses resultados sugerem que existe uma associação entre atividade física e níveis reduzidos de MDA em FG. O exercício físico parece promover efeitos benéficos no PL independente da influência genética considerando os níveis de HDLc.

OBJECTIVE: To evaluate whether lipid profile (LP), apolipoprotein A-1 (apo A-I) and malondialdehyde (MDA) have any relationship with physical exercise by comparing the groups of footballers (FG) with sedentary individuals (CG) and their relatives (RFG and RCG). SUBJECTS AND METHODS: Twenty individuals from FG and CG, 60 from RFG, and 57 from RCG were studied. RESULTS: FG showed lower levels of total cholesterol (119.5 ± 37.9 mg/dL), LDL-cholesterol fraction (53.6 ± 30.3), apo A-I (116.7 ± 11.9), and higher level of HDL-cholesterol fraction (HDLc) (49.7 ± 8.5) compared to RFG (148.3 ± 36.9, P = 0.02; 82.4 ± 37.7, P < 0.01; 124.6 ± 10.2, P = 0.03; and 42.7 ± 7.7, P < 0.01; respectively). Moreover, FG had reduced levels of MDA (101.0 ± 77.0 ng/mL) compared to CG (290.0 ± 341.0, P = 0.03) and RFG (209.9 ± 197.5, P = 0.04). CONCLUSIONS: These results suggest an association between physical exercise and lower levels of MDA in FG. Physical activity seems to promote beneficial effects on the LP regardless of the genetic influence considering HDLc levels.

An inflammatory process has been involved in numerous neurodegenerative disorders such as Parkinson's disease, stroke and Alzheimer's disease (AD). In AD, the inflammatory response is mainly located in the vicinity of amyloid plaques. Cytokines, such as interleukin-8 (IL-8) and interleukin-1α (IL-1α), have been clearly involved in this inflammatory process. Polymorphisms of several interleukin genes have been correlated to the risk of developing AD. The present study investigated the association of AD with polymorphisms IL-8 -251T > A (rs4073) and IL-1α-889C > T (rs1800587) and the interactive effect of both, adjusted by the Apolipoprotein E genotype. 199 blood samples from patients with AD, 146 healthy elderly controls and 95 healthy young controls were obtained. DNA samples were isolated from blood cells, and the PCR-RFLP method was used for genotyping. The genotype distributions of polymorphisms IL-8, IL-1α and APOE were as expected under Hardy-Weinberg equilibrium. The allele frequencies did not differ significantly among the three groups tested. As expected, the APOE4 allele was strongly associated with AD (p < 0.001). No association of AD with either the IL-1α or the IL-8 polymorphism was observed, nor was any interactive effect between both polymorphisms. These results confirm previous studies in other populations, in which polymorphisms IL-8 -251T > A and IL-1α-889C > T were not found to be risk factors for AD.

Physical exercise and statins, which are recommended for the treatment of dyslipidemia, are independently associated to the occurrence of muscle injury. The objective is analyze the effect of aerobic exercise associated to the use of simvastatin on the morphology of the gastrocnemius muscle. Thirty Wistar rats were divided into six groups, two of which received a standard diet (1 sedentary and 1 exercised) and four (1 sedentary with medication, 1 sedentary without medication, 1 exercised with medication, 1 exercised without medication) received a hypercholesterolemic diet (standard diet with the addition of cholesterol and coconut oil). Simvastatin (20 mg/Kg) was administered five days a week for eight weeks, together with aerobic training on a treadmill (9.75 m/min) for 60 minutes a day. The gastrocnemius muscle was removed, sliced, stained with Hematoxylin-Eosin and submitted to a histochemical reaction to determine mitochondrial activity. The data were analyzed using a paired t-test, analysis of variance and Scheffé's post hoc test (p<0.05). Greater histological alterations were found in the medicated and exercised animals, with a greater frequency of occurrence as well. The histochemical analysis revealed that the medicated groups had fibers with more intensive mitochondrial activity alongside fibers with an absence of reaction. The morphometric analysis revealed no significant differences between groups. It is suggested that simvastatin is a medication that leads to the occurrence of muscle injury and its administration in association with physical activity may exacerbate these injuries. This finding may be related to cellular respiration.

El ejercicio físico y las estatinas, son intervenciones recomendadas para el tratamiento de la dislipidemia y están independientemente asociadas con la ocurrencia de lesiones musculares. El objetivo fue analizar el efecto del ejercicio aeróbico asociado al uso de la sinvastatina en la morfología del músculo gastrocnemio. 30 ratas macho Wistar fueron divididos en 6 grupos, de los cuales 2 recibieron ración padrón, sedentarios, ejercitados y 4 recibieron dieta con alto nivel de colesterol, sedentarios con y sin medicamento, ejercitados con y sin medicamentos. La dieta fue elaborada a partir de una dieta padrón aumentada de colesterol y aceite de coco. La Sinvastatina (20 mg) fue administrada por 5 días por semana durante 8 semanas (20 mg/kg), junto al entrenamiento aeróbico en la estera (9,75 m/min) por 60 minutos por día. El músculo gastrocnemio colectado fue cortado y colorido por el método Hematoxilina-Eosina y sometido a una reacción histoquímica para verificar la actividad mitocondrial. Los datos fueron analizados utilizando el test t pareado, análisis de la variancia e Pos-Hoc de Scheffé, adoptándose p<0,05. Se verifico la presencia de alteraciones histológicas más significativas en los animales medicados y ejercitados, siendo también mayor la frecuencia de ocurrencia. El análisis histoquímica apunto que los grupos medicados presentaron fibras con actividad mitocondrial más intensa, al lado de fibras con pérdida de reacción. Los resultados de la morfometría no mostraron diferencias significativas entre los grupos estudiados. Se puede sugerir que la simvastatina es un medicamento que lleva a la ocurrencia de lesiones musculares e que su administración concomitante con la práctica de actividad física puede exacerbar estas lesiones, pudiendo tal hecho, estar relacionado con la respiración celular.

Physical exercise and statins, recommended interventions to dyslipidaemia treatment, are independently related to cardiomyocytes alterations, characterized by miocardic hypertrophy and apoptosis, respectively. Thus, the objective of the present study was to analyze the effects of statin and aerobic physical exercise association in the morphometric parameters of cardiac cell nucleus. 40 male rats adults were divided into four groups: exercised (DE); sedentary (DS), exercised and statin use (DES); sedentary and statin use (DSS). The animals received during the whole experimental period a hiperlipidic diet added 20% of coconut oil and 1.25% of cholesterol; after 30 days of its ingestión, a blood collection was made to verify the dyslipidaemia. Simvastatin (20 mg) was taken five days a week, during eight weeks. During this period, the animals exercised 60 minutes daily in the treadmill. After the last day of the protocol, the cardiac muscle was collected and maintained in liquid nitrogen (-180°C); the cuts were stained by Hematoxilin-Eosin method, and the cardiac fibers were submitted to the nuclear morphometric analyses. The data were analyzed using descriptive analyses, paired T test, Kruskal-Wallis test and Dunn post hoc test; for all analyses, it was adopted p<0.05. It was verified that the group receiving statin presented values statistically significant in comparison to the other groups, in the tridimensional and linear variables. The exercised and statin group, the values obtained in the morphometric analyses were similar to the control group. It is suggested that statins alone can cause alterations in the nucleus of cardiac cells that can be related to apoptosis occurrence and, when exercise is practiced associated to statin administration, the effects of statin can be reduced, what can be related to beneficial adaptations of cardiac mitochondrial in response to physical exercise, turning them more resistant to apoptotic stimuli.

El ejercicio físico y las estatinas, intervenciones recomendadas para tratamiento de la dislipidemia, están independientemente relacionadas con las alteraciones de los cardiomiocitos, que se caracterizan por hipertrofia miocárdica y apoptosis, respectivamente. El objetivo del presente estudio fue analizar los efectos de la asociación de estatinas y el ejercicio físico aeróbico en los parámetros morfométricos del núcleo de células cardíacas. 40 ratas macho adultas se dividieron en cuatro grupos: ejercitadas (DE); sedentarias (DS), ejercitadas y con uso de estatina (DES), sedentarias y con uso de estatina (DSS). Los animales recibieron durante todo el período experimental una dieta hiperlipidemica añadiendo 20% de aceite de coco y 1,25% de colesterol. Después de 30 días de su ingestión, se les extrajo sangre para verificar la dislipidemia. Los ejemplares ingirieron Simvastatina (20 mg) cinco días a la semana, durante ocho semanas. Durante este período, los animales ejercitaron 60 minutos diarios en la rueda de andar. Después del último día del protocolo,los animales fueron sacrificados y se les extrajo músculo cardiaco que fue mantenido en nitrógeno líquido (-180°C). De este material se obtuvieron cortes que fueron teñidos por el método de hematoxilina-eosina y las fibras cardiacas fueron sometidas a análisis morfométrico nuclear. Los datos fueron analizados mediante el análisis descriptivo, prueba de la t de Student, prueba de Kruskal-Wallis y Dunn test post hoc. Para todos los análisis fue aprobado p <0,05. Se comprobó que el grupo que recibió estatinas presentó valores estadísticamente significativos en comparación con los otros grupos, en las variables lineales y tridimensionales. En el grupo ejercitado y estatina, los valores obtenidos de los análisis morfométricos fueron similares a los del grupo control. Se sugiere que las estatinas, por sí solas, pueden causar alteraciones en el núcleo de las células cardiacas las cuales pueden estar relacionadas con la ocurrencia de apoptosis y, cuando se practica ejercicio asociado a la administración de estatina, los efectos de las estatinas pueden reducirse, pudiendo resultar beneficioso, en relación con las adaptaciones en la respuesta mitocondrial cardiaca al ejercicio físico, convirtiéndose en más resistentes a los estímulos de apoptosis.