5,869 research outputs found
Lipolysis and lipophagy in lipid storage myopathies
No full textAbstractAimsTriglycerides droplets are massively stored in muscle in Lipid Storage Myopathies (LSM). We studied in muscle regulators of lipophagy, the expression of the transcription factor-EB (TFEB) (a master regulator of lysosomal biogenesis), and markers of autophagy which are induced by starvation and exert a transcriptional control on lipid catabolism.MethodsWe investigated the factors that regulate lipophagy in muscle biopsies from 6 patients with different types of LSM: 2 cases of riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD), 1 case of primary carnitine deficiency (CD), 2 cases of neutral lipid storage myopathy (NLSD-M), 1 case of carnitine–palmitoyl-transferase-II (CPT) deficiency.ResultsConventional morphology and electron microscopy documented the lipid accumulation and its dramatic resolution after treatment. Muscle immunofluorescence showed that while in MADD and NLSD-M there was a co-localized expression of TFEB and p62-SQSTM1 (marker of protein aggregates) in some atrophic fibers, in CD and CPT-II deficiency the reaction was almost normal. In regenerating fibers, TFEB localized in the cytoplasm (inactive form), whereas in atrophic fibers it localized in the nuclei (active form). Lipid-accumulated/atrophic fibers did not display p62-positive protein aggregates, indicating, together with the LC3-II (marker of autophagosomes) and p62-SQSTM1 analysis, that the autophagic flux is often preserved and lipophagy occurs.ConclusionIn atrophic and regenerating fibers of patients with NLSD-M we observed TFEB over-expression; in other conditions autophagy markers are increased, suggesting lipophagy active role on human lipid metabolism
Neuronal Nitric Oxide Synthase (nNOS) activity and ultrastructural changes in caveolin-3 deficient muscle cause mechanical irritability.
No full textSarcolemmal Neuronal Nitric Oxide Synthase Defect in Limb-Girdle Muscular Dystrophy: An Adverse Modulating Factor in the Disease Course?
No full text
Long-term follow-up results in enzyme replacement therapy for Pompe disease: a case report
No full textJ Inherit Metab Dis. 2010 Sep 10. [Epub ahead of print]
Long-term follow-up results in enzyme replacement therapy for Pompe disease: a case report.
Del Rizzo M, Fanin M, Cerutti A, Cazzorla C, Milanesi O, Nascimbeni AC, Angelini C, Giordano L, Bordugo A, Burlina AB.
Source
Division of Metabolic Diseases, Department of Paediatrics, University Hospital Padua, Via Giustiniani 3, 35128, Padua, Italy.
Abstract
Pompe disease (PD) is a metabolic myopathy caused by a deficiency of acid-alpha glucosidase (GAA), a lysosomal enzyme that cleaves glycogen. The classic infantile-onset form is characterised by severe hypotonia and cardiomyopathy. Untreated patients usually die within the first year of life due to cardiorespiratory failure. Several studies involving patients with infantile-onset PD have shown that enzyme replacement therapy (ERT) with alglucosidase alfa, recombinant human GAA (rhGAA), significantly prolongs survival, decreases cardiomegaly, and improves cardiac function and conduction abnormalities. However, the efficacy on motor, cognitive and social milestones appears to be more related to the condition of the patient before the start of treatment. To date, the sample of early diagnosed and treated patients is small and the length of follow-up is still limited. We report the results of a long-term follow-up of one patient presenting severe bradycardia and cardiomyopathy at birth, diagnosed in the third day of life and successfully treated by ERT. Serum muscle enzymes at diagnosis were AST 200 U/L, ALT 99 U/L and CPK 731 U/L (n.v. 0-295); the molecular study identified the homozygous missense mutation c.1933 G> A p.Asp645Asn (GAA exon 14). Left Ventricular Mass Index (LVMI) at baseline was 171 g/m(2) (Z-score = 4.3) and decreased to normal values since the 3-month follow-up. A muscle biopsy performed at 18 months after the start of therapy, showed only a low degree of muscle involvement. To our knowledge, this is the longest ERT treatment follow-up in a symptomatic neonatal patient with Pompe disease.
PMID:
20830524
[PubMed - as supplied by publisher
Influence of ac ageing on space charge dynamics in LDPE
No full textPolymeric materials have been widely used as insulation in power industry due to their excellent electrical properties. However, these properties deteriorate in time irreversibly when the material is subjected to electric stress. Although space charge is believed to play an important role in ac ageing, exact mechanisms are poorly understood due to very limited experimental data. In the present work efforts have been made to investigate the influence of ac ageing on space charge dynamics in low-density polyethylene (LDPE). LDPE films with 200mm were aged at 50 kV/mm at 50 Hz for various times at ambient temperature. Space charge dynamics in the samples prior to and after ageing were monitored using the pulsed electroacoustic (PEA) technique under dc electric stress. The results indicate that there is a significant amount of homocharge accumulation in the unaged sample due to charge injection. These injected charges are the captured by the deep traps originated from the interface between crystalline and amorphous regions in LDPE. Ageing under ac condition does not necessarily lead to an increase in amount of charge in the bulk but leads to an increase in mobility of charge carriers. Chemical analysis by infrared spectroscope (FTIR) reveals there are chemical changes taken place in the bulk of the material after ac ageing. It is believed that the chemical changes introduce shallow traps which promote the movement of charge carriers in the bulk. Consequently, the injected charges spread across the sample
- …
