Duchenne's muscular dystrophy involves a defective transsulfuration pathway activity

Duchenne muscular dystrophy (DMD) is the most frequent X chromosome-linked disease caused by mutations in the gene encoding for dystrophin, leading to progressive and unstoppable degeneration of skeletal muscle tissues. Despite recent advances in the understanding of the molecular processes involved in the pathogenesis of DMD, there is still no cure. In this study, we aim at investigating the potential involvement of the transsulfuration pathway (TSP), and its by-end product namely hydrogen sulfide (H2S), in primary human myoblasts isolated from DMD donors and skeletal muscles of dystrophic (mdx) mice. In myoblasts of DMD donors, we demonstrate that the expression of key genes regulating the H2S production and TSP activity, including cystathionine γ lyase (CSE), cystathionine beta-synthase (CBS), 3 mercaptopyruvate sulfurtransferase (3-MST), cysteine dioxygenase (CDO), cysteine sulfonic acid decarboxylase (CSAD), glutathione synthase (GS) and γ -glutamylcysteine synthetase (γ-GCS) is reduced. Starting from these findings, using Nuclear Magnetic Resonance (NMR) and quantitative Polymerase Chain Reaction (qPCR) we show that the levels of TSP-related metabolites such as methionine, glycine, glutathione, glutamate and taurine, as well as the expression levels of the aforementioned TSP related genes, are significantly reduced in skeletal muscles of mdx mice compared to healthy controls, at both an early (7 weeks) and overt (17 weeks) stage of the disease. Importantly, the treatment with sodium hydrosulfide (NaHS), a commonly used H2S donor, fully recovers the impaired locomotor activity in both 7 and 17 old mdx mice. This is an effect attributable to the reduced expression of pro-inflammatory markers and restoration of autophagy in skeletal muscle tissues. In conclusion, our study uncovers a defective TSP pathway activity in DMD and highlights the role of H2S-donors for novel and safe adjuvant therapy to treat symptoms of DMD

Hybrid approach for aortic arch and thoraco-abdominal aneurysm: a new era?

TEVAR OFFERS THE ADVANTAGE OF A LESS INVASIVE TREATMENT, REDUCING THE RISK OF PARAPLEGIA,VISCERL ISCHAEMIA AND PULMONARY COMPLICATION. THE HYBRID APRROACH DON'T PRECLUDE THE POSSIBILITY OF A SECONDARY TEVAR OR OF A CONVETIONAL SURGERY OF AORTIC PATHOLOGIE

IMPACT OF BLOOD COAGULATION AND FIBRINOLYTIC SYSTEM CHANGES ON EARLY AND MID TERM CLINICAL OUTCOME IN PA-TIENTS UNDERGOING STENT ENDOGRAFTING SURGERY.

Objective: Blood coagulation and fibrinolytic system changes after endovascular repair (EVAR) of aortic pathologies are of great interest. We have examined the risk for consumption coagulopathy and its clinical implications early, and at a mid-term follow-up, in a prospective study. Methods: From June 2002 to June 2004, 41 patients for abdominal aortic aneurysm (AAA), 16 for thoracic aortic aneurysm (TAA) and 13 for acute type-B dissection underwent EVAR. Plasminogen, fibrin degradation products (FDP) and D-dimer were monitored as markers of fibrinolysis. Platelet count, fibrinogen, antithrombin III and prothrombin were assayed as markers of coagulation. The aortic diameters were assessed by computed tomography (CT) scan. Results: FDP and D-Dimer levels significantly increased, while plasminogen values significantly decreased, on postoperative day 1 and 5, coagulation parameters significantly decreased on postoperative day 1 and 5. All parameters recovered on the 1st month of follow-up, except fibrinogen levels that showed a significant increase on month 1 and 6. We did not observe clinical complications related to coagulative disorders. There was no correlation between the preoperative diameter and the coagulative and fibrinolysis variations in the AAA and TAA group. Type-B dissection patients showed a significant correlation between the preoperative presence of a large false lumen and a high level of fibrinolysis. Conclusion: EVAR leads to changes in coagulation and fibrinolysis, with characteristic developments. These latter have no clinical relevance and have no effect on early outcome and on midterm follow-up. \uc2\ua9 2006 Published by European Association for Cardio-Thoracic Surgery. All rights reserved