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Samir MandalSudip Mukherjee Kaustav Dutta ChowdhuryAvik Sarkar Kankana BasuSoumosish Paul Debasish KarmakarMahasweta Chatterjee Tuli BiswasGobinda Chandra Sadhukhan Gargi Sen 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012,1820(1):9-23
Background
Chronic lead (Pb2 +) exposure leads to the reduced lifespan of erythrocytes. Oxidative stress and K+ loss accelerate Fas translocation into lipid raft microdomains inducing Fas mediated death signaling in these erythrocytes. Pathophysiological-based therapeutic strategies to combat against erythrocyte death were evaluated using garlic-derived organosulfur compounds like diallyl disulfide (DADS), S allyl cysteine (SAC) and imidazole based Gardos channel inhibitor clotrimazole (CLT).Methods
Morphological alterations in erythrocytes were evaluated using scanning electron microscopy. Events associated with erythrocyte death were evaluated using radio labeled probes, flow cytometry and activity gel assay. Mass spectrometry was used for detection of GSH-4-hydroxy-trans-2-nonenal (HNE) adducts. Fas redistribution into the lipid rafts was studied using immunoblotting technique and confocal microscopy.Results
Combination of SAC and CLT was better than DADS and CLT combination and monotherapy with these agents in prolonging the survival of erythrocytes during chronic Pb2 + exposure. Combination therapy with SAC and CLT prevented redistribution of Fas into the lipid rafts of the plasma membrane and downregulated Fas-dependent death events in erythrocytes of mice exposed to Pb2 +.Conclusion and general significance
Ceramide generation was a critical component of Fas receptor-induced apoptosis, since inhibition of acid sphingomyelinase (aSMase) interfered with Fas-induced apoptosis during Pb2 + exposure. Combination therapy with SAC and CLT downregulated apoptotic events in erythrocytes by antagonizing oxidative stress and Gardos channel that led to suppression of ceramide-initiated Fas aggregation in lipid rafts. Hence, combination therapy with SAC and CLT may be a potential therapeutic option for enhancing the lifespan of erythrocytes during Pb2 + toxicity. 相似文献4.
Yasmin Farhatnia Aaron Tan Aamir Motiwala Brian G. Cousins Alexander M. Seifalian 《Biotechnology advances》2013
Endovascular stents have revolutionised the field of interventional cardiology. Despite their excellent clinical outcome complications associated with percutaneous stent implantation following the procedure have remained a major drawback in their widespread use. To overcome such limitations, a number of novel endovascular stents have emerged including a covered stent wrapped in a thin membrane sleeve. As well as prevention of complications associated with stenting, covered stents owing to their physical barrier are used as the treatment option of choice for trauma devices during emergency situations and to treat a number of pathological disease states. The aim of this review is to provide the reader with an overall objective outlook in the use of covered stents as a treatment option in a number of vascular complications and addresses their design and materials used in the manufacturing process. In addition, new strategies are highlighted and future prospects with the emergence of novel smart alloys for 3D scaffolds and the use of nanotechnology in the development of nanocomposite materials. 相似文献
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