Objective. We evaluated the influence of exercise on functional capacity, cardiac remodeling, and skeletal muscle oxidative stress, MAPK, and NF-κB pathway in rats with aortic stenosis- (AS-) induced heart failure (HF). Methods and Results. Eighteen weeks after AS induction, rats were assigned into sedentary control (C-Sed), exercised control (C-Ex), sedentary AS (AS-Sed), and exercised AS (AS-Ex) groups. Exercise was performed on treadmill for eight weeks. Statistical analyses were performed with Goodman and ANOVA or Mann-Whitney. HF features frequency and mortality did not differ between AS groups. Exercise improved functional capacity, assessed by maximal exercise test on treadmill, without changing echocardiographic parameters. Soleus cross-sectional areas did not differ between groups. Lipid hydroperoxide concentration was higher in AS-Sed than C-Sed and AS-Ex. Activity of antioxidant enzymes superoxide dismutase and glutathione peroxidase was changed in AS-Sed and restored in AS-Ex. NADPH oxidase activity and gene expression of its subunits did not differ between AS groups. Total ROS generation was lower in AS-Ex than C-Ex. Exercise modulated MAPK in AS-Ex and did not change NF-κB pathway proteins. Conclusion. Exercise improves functional capacity in rats with AS-induced HF regardless of echocardiographic parameter changes. In soleus, exercise reduces oxidative stress, preserves antioxidant enzyme activity, and modulates MAPK expression.

Calorie restriction is a dietary intervention known to improve redox state, glucose tolerance, and animal life span. Other interventions have been adopted as study models for caloric restriction, including nonsupplemented food restriction and intermittent, every-other-day feedings. We compared the short- and long-term effects of these interventions to ad libitum protocols and found that, although all restricted diets decrease body weight, intermittent feeding did not decrease intra-abdominal adiposity. Short-term calorie restriction and intermittent feeding presented similar results relative to glucose tolerance. Surprisingly, long-term intermittent feeding promoted glucose intolerance, without a loss in insulin receptor phosphorylation. Intermittent feeding substantially increased insulin receptor nitration in both intra-abdominal adipose tissue and muscle, a modification associated with receptor inactivation. All restricted diets enhanced nitric oxide synthase levels in the insulin-responsive adipose tissue and skeletal muscle. However, whereas calorie restriction improved tissue redox state, food restriction and intermittent feedings did not. In fact, long-term intermittent feeding resulted in largely enhanced tissue release of oxidants. Overall, our results show that restricted diets are significantly different in their effects on glucose tolerance and redox state when adopted long-term. Furthermore, we show that intermittent feeding can lead to oxidative insulin receptor inactivation and glucose intolerance.

Mutations in the gene encoding cytosolic Cu,Zn-superoxide dismutase (SOD1) have been linked to familial amyotrophic lateral sclerosis (FALS). However the molecular mechanisms of motor neuron death are multi-factorial and remain unclear. Here we examined DNA damage, p53 activity and apoptosis in SH-SY5Y human neuroblastoma cells transfected to achieve low-level expression of either wild-type or mutant Gly(93)-->Ala (G93A) SOD1, typical of FALS. DNA damage was investigated by evaluating the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and DNA strand breaks. Significantly higher levels of DNA damage, increased p53 activity, and a greater percentage of apoptotic cells were observed in SH-SY5Y cells transfected with G93A SOD1 when compared to cells overexpressing wild-type SOD1 and untransfected cells. Western blot, FACS, and confocal microscopy analysis demonstrated that G93A SOD1 is present in the nucleus in association with DNA. Nuclear G93A SOD1 has identical superoxide dismutase activity but displays increased peroxidase activity when compared to wild-type SOD1. These results indicate that the G93A mutant SOD1 association with DNA might induce DNA damage and trigger the apoptotic response by activating p53. This toxic activity of mutant SOD1 in the nucleus may play an important role in the complex mechanisms associated with motor neuron death observed in ALS pathogenesis.

Epidemiological studies testing the e¡ect of L L-carotene in humans have found a relative risk for lung cancer in smokers supplemented with L L-carotene. We investigated the reactions of retinal and L L-apo-8P P-carotenal, two L L-carotene oxidation products, with 2P P-deoxyguanosine to evaluate their DNA damaging potential. A known mutagenic adduct, 1,N 2 -etheno-2P P-deoxyguanosine, was isolated and characterized on the basis of its spectroscopic features. After treatment of calf thymus DNA with L L-carotene or L L-carotene oxidation products, signi¢-cantly increased levels of 1,N 2 -etheno-2P P-deoxyguanosine and 8-oxo-7,8-dihydro-2P P-deoxyguanosine were quanti¢ed in DNA. These lesions are believed to be important in the development of human cancers. The results reported here may contribute toward an understanding of the biological e¡ects of L L-carotene oxidation products. ß

RESUMO:Este estudo teve como objetivo investigar na perspectiva de cuidadores familiares de idosos com provável/possível diagnóstico da doença de Alzheimer: a reação inicial da família diante do provável/possível diagnóstico da doença de Alzheimer; as principais atividades realizadas com estes idosos; as fontes de auxílio no cuidado e o grau de satisfação em relação a esse auxílio; os sentimentos vivenciados diante da tarefa de cuidar e a dinâmica familiar após a enfermidade. A amostra foi composta por 17 cuidadores familiares que contaram com o auxílio da Associação de Familiares e Amigos dos Idosos (AFAI). Os dados foram coletados por meio de um questionário com perguntas abertas e fechadas. Os resultados demonstraram que a reação inicial dos familiares foi desfavorável diante do provável/possível diagnóstico da DA e com a progressão da doença, os cuidadores vivenciaram sentimentos desfavoráveis diante da tarefa de cuidar, desencadeando mudanças na dinâmica familiar.Palavras-chave: Doença de Alzheimer; Cuidador; Família.