Muscle fatigue,nNOS and muscle fiber atrophy in limb girdle muscular dystrophy

Muscle fatigability and atrophy are frequent clinical signs in limb girdle muscular dystrophy (LGMD), but their pathogenetic mechanisms are still poorly understood.We review a series of different factors that may be connected in causing fatigue and atrophy, particularly considering the role of neuronal nitric oxide synthase (nNOS) and additional factors such as gender in different forms of LGMD (both recessive and dominant) underlying different pathogenetic mechanisms.In sarcoglycanopathies, the sarcolemmal nNOS reactivity varied from absent to reduced, depending on the residual level of sarcoglycan complex: in cases with complete sarcoglycan complex deficiency (mostly in beta-sarcoglycanopathy), the sarcolemmal nNOS reaction was absent and it was always associated with early severe clinical phenotype and cardiomyopathy.Calpainopathy, dysferlinopathy, and caveolinopathy present gradual onset of fatigability and had normal sarcolemmal nNOS reactivity. Notably, as compared with caveolinopathy and sarcoglycanopathies, calpainopathy and dysferlinopathy showed a higher degree of muscle fiber atrophy.Males with calpainopathy and dysferlinopathy showed significantly higher fiber atrophy than control males, whereas female patients have similar values than female controls, suggesting a gender difference in muscle fiber atrophy with a relative protection in females. In female patients, the smaller initial muscle fiber size associated to endocrine factors and less physical effort might attenuate gender-specific muscle loss and atrophy.Key words: LGMD, nNOS, sarcoglycan     

Granulocyte—macrophage colony stimulating factor in acute non-lymphocytic leukaemia

Abstract. Background. Granulocyte-macrophage colony stimulating factor (GM-CSF) is required to maintain and to regulate granulocyte and monocyte productions. It is potentially useful for accelerating and enhancing haemopoietic recovery and neutrophil function. Results. In acute non-lymphocytic leukaemia (ANLL) the dependence of blast cells on GM-CSF and its role in the development and maintenance of leukaemia are still poorly defined. In vitro exposure of fresh leukaemic blast cells to a wide range of concentrations of GM-CSF leads to a stimulation of cell proliferation in the majority of cases but does not induce any detectable maturation. Conclusions. Granulocyte-macrophage colony stimulating factor may be used in the management of ANLL and the myelodysplastic syndrome (MDS) with the aim of: (i) accelerating the recovery of normal haemopoiesis; (ii) increasing cell killing by chemotherapy; and (iii) inducing cell maturation. Therefore the application of GM-CSF can potentially improve treatment outcome in ANLL and is worth testing in a clinical setting.