Myosin light chains and muscle pathology

We evaluated the isoform composition of heavy and light chains of myosin in single muscle fibers from patients with Duchenne dystrophy, myotonic dystrophy, or polymyositis. In all myopathic muscles, there was an increase in the proportion of intermediate fibers which, by analysis of myosin isoforms, fell into two subpopulations, one that contained both fast and slow myosin and another that contained myosin molecular hybrids. The increased proportion of intermediate (or transitional) fibers suggests changes in the equilibrium between fast and slow motor units. These changes could result from regeneration and subsequent maturation of fibers or from direct transformation of mature fibers of one type into the opposite.     

Older adults’ preferences for exercising alone versus in groups: Considering contextual congruence

Background: A growing body of research suggests that older exercisers prefer to exercise alone rather than in group-based settings. One limitation of these studies, however, has been that researchers have failed to take into account the age-related characteristics of groups when asking adults about their preferences for exercise settings.Purpose: The overall purpose of this study was to examine the exercise preferences of 947 adults for involvement in standard exercise classes populated by participants from various categories across the age spectrum.Results: The results revealed that when faced with the prospect of exercising with considerably older or younger exercisers, participants found such an exercise context to be largely unappealing. However, in accordance with the basic tenets of self-categorization theory, the results revealed that older and younger adults alike express a positive preference for exercising in standard exercise classes comprised of similarly aged participants.Conclusions: The findings of this study challenge a growing call for exercise interventions for older adults to be primarily directed at the individual-level, and suggest that group-related intervention strategies may indeed be attractive to older exercisers.     

Early increase of oxidative stress and soluble CD40L in children with hypercholesterolemia.

OBJECTIVES: The aim of the study was to analyze the behavior of oxidative stress and its interplay with CD40L, a protein that is implicated in atherosclerosis, in hypercholesterolemic children. BACKGROUND: Oxidative stress has been suggested to play a major role in premature atherosclerosis. METHODS: Forty-one children with hypercholesterolemia (mean age 9.28 +/- 0.5 years) and 40 children with normocholesterolemia (mean age 9.02 +/- 0.69 years) were matched for gender and age. Within each group, children were classified as having or not having a family history of cardiovascular disease. Serum levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, and plasma levels of soluble CD40L (sCD40L) were measured in each child. In a subgroup of children with high (n = 8) or normal (n = 8) levels of serum cholesterol, platelet p38 mitogen-activated protein (MAP) kinase phosphorylation, a protein involved in the activation of nicotinamide adenine dinucleotide phosphate oxidase, was determined. RESULTS: Children with hypercholesterolemia had higher values of 8-OHdG and sCD40L compared with control subjects (0.55 +/- 0.06 ng/ml vs. 0.21 +/- 0.02 ng/ml, p < 0.001 and 0.55 +/- 0.04 ng/ml vs. 0.19 +/- 0.03 ng/ml, p < 0.001, respectively). A significant correlation between 8-OHdG and sCD40L was observed in children with high (r = 0.676, p < 0.001) or normal (r = 0.878, p < 0.001) levels of cholesterol. Children with a family history of cardiovascular disease tended to have higher values of 8-OHdG and sCD40L, but the difference was not significant. Analysis of platelet p38 MAP kinase showed that it was phosphorylated more in children with hypercholesterolemia compared with control subjects (36.8 +/- 5.8 AU vs. 8.0 +/- 4.5 AU, p < 0.001 respectively). CONCLUSIONS: Children with hypercholesterolemia have an early increase of oxidative stress that may be responsible for up-regulation of CD40L and potentially predispose to premature atherosclerosis.     

Vitamin E affects cell death in adult rat dentate gyrus

We have previously reported the presence of dying cells in the granule cell layer (GCL) of adult rat dentate gyrus (DG), where neurogenesis occurs. In particular, we found that cell death in the GCL increased in vitamin E deficiency and decreased in vitamin E supplementation. These findings were regarded as related to changes in neurogenesis rate, which in turn was influenced by vitamin E availability; a neuroprotective effect of vitamin E on cell death was also proposed. In order to verify this latter hypothesis, we have studied cell death in all layers of DG in vitamin E-deficient and vitamin E-supplemented rats and in control rats at different ages, using TUNEL and nick translation techniques. The phenotype of TUNEL-positive cells was characterized and the existence of dying BrdU-positive cells was investigated. Dying cells with neuronal phenotype were observed throughout the DG in all experimental groups. The number of TUNEL-positive cells decreased from juvenile to adult age. A higher number of TUNEL-positive cells in vitamin E-deficient rats and a lower number in vitamin E-supplemented rats, with respect to age-matched controls, were found; moreover, in these groups, TUNEL-positive cells had a different percentage distribution in the different layers of the DG. Our results confirm the occurrence of cell death in DG, demonstrate that cell death affects neuronal cells and support the hypothesis that the effect of vitamin E on cell death is not related to neurogenesis.     

Improved survival of ischemic cutaneous and musculocutaneous flaps after vascular endothelial growth factor gene transfer using adeno-associated virus vectors

A major challenge in reconstructive surgery is flap ischemia, which might benefit from induction of therapeutic angiogenesis. Here we demonstrate the effect of an adeno-associated virus (AAV) vector delivering vascular endothelial growth factor (VEGF)165 in two widely recognized in vivo flap models. For the epigastric flap model, animals were injected subcutaneously with 1.5 x 10(11) particles of AAV-VEGF at day 0, 7, or 14 before flap dissection. In the transverse rectus abdominis musculocutaneous flap model, AAV-VEGF was injected intramuscularly. The delivery of AAV-VEGF significantly improved flap survival in both models, reducing necrosis in all treatment groups compared to controls. The most notable results were obtained by administering the vector 14 days before flap dissection. In the transverse rectus abdominis musculocutaneous flap model, AAV-VEGF reduced the necrotic area by >50% at 1 week after surgery, with a highly significant improvement in the healing process throughout the following 2 weeks. The therapeutic effect of AAV-VEGF on flap survival was confirmed by histological evidence of neoangiogenesis in the formation of large numbers of CD31-positive capillaries and alpha-smooth muscle actin-positive arteriolae, particularly evident at the border between viable and necrotic tissue. These results underscore the efficacy of VEGF-induced neovascularization for the prevention of tissue ischemia and the improvement of flap survival in reconstructive surgery.