207 research outputs found

    Targeting liver myofibroblasts: a novel approach in anti-fibrogenic therapy

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    Chronic liver disease results in a liver-scarring response termed fibrosis. Excessive scarring leads to cirrhosis, which is associated with high morbidity and mortality. The only treatment for liver cirrhosis is liver transplantation; therefore, much attention has been directed toward therapies that will slow or reverse fibrosis. Although anti-fibrogenic therapies have been shown to be effective in experimental animal models, licensed therapies have yet to emerge. A potential problem for any anti-fibrogenic therapy in the liver is the existence of the body’s major drug metabolising cell (the hepatocyte) adjacent to the primary fibrosis-causing cell, the myofibroblast. This article reviews the development of a human recombinant single-chain antibody (scAb) that binds to the surface of myofibroblasts. This antibody binds specifically to myofibroblasts in fibrotic mouse livers. When conjugated with a compound that stimulates myofibroblast apoptosis, the antibody directs the specific apoptosis of myofibroblasts with greater specificity and efficacy than the free compound. The antibody also reduces the adverse effect of liver macrophage apoptosis and—in contrast to the free compound—reversed fibrosis in the sustained injury model used. These data suggest that specifically stimulating the apoptosis of liver myofibroblasts using a targeting antibody has potential in the treatment of liver fibrosis

    Radiofrequency cardiac ablation with catheters placed on opposing sides of the ventricular wall: Computer modelling comparing bipolar and unipolar modes

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    Purpose: The aim of this study was to compare the efficacy of bipolar (BM) vs. unipolar (UM) mode of radiofrequency ablation (RFA) in terms of creating transmural lesions across the interventricular septum (IVS) and ventricular free wall (VFW). Materials and methods: We built computational models to study the temperature distributions and lesion dimensions created by BM and UM on IVS and VFW during RFA. Two different UM types were considered: sequential (SeUM) and simultaneous (SiUM). The effect of ventricular wall thickness, catheter misalignment, epicardial fat, and presence of air in the epicardial space were also studied. Results: Regarding IVS ablation, BM created transmural and symmetrical lesions for wall thicknesses up to 15 mm. SeUM and SiUM were not able to create transmural lesions with IVS thicknesses >= 12.5 and 15 mm, respectively. Lesions were asymmetrical only with SeUM. For VFW ablation, BM also created transmural lesions for wall thicknesses up to 15 mm. However, with SeUM and SiUM transmurality was obtained for VFW thicknesses <= 7.5 and 12.5 mm, respectively. With the three modes, VFW lesions were always asymmetrical. In the scenario with air or a fat tissue layer on the epicardial side, only SiUM was capable of creating transmural lesions. Overall, BM was superior to UM in IVS and VFW ablation when the catheters were not aligned. Conclusions: Our findings suggest that BM is more effective than UM in achieving transmurality across both ventricular sites, except in the situation of the epicardial catheter tip surrounded by air or placed over a fat tissue layer.This work received financial support from the Spanish 'Plan Nacional de I+D+I del Ministerio de Ciencia e Innovacion' (TEC2011-27133-C02-01), and from the Universitat Politecnica de Valencia (PAID-06-11 Ref. 1988). A. Gonzalez-Suarez is the recipient of a Grant VaLi+D (ACIF/2011/194) from the Generalitat Valenciana, Spain. The authors alone are responsible for the content and writing of the paper.González Suárez, A.; Trujillo Guillen, M.; Koruth, J.; D'avila, A.; Berjano, E. (2014). Radiofrequency cardiac ablation with catheters placed on opposing sides of the ventricular wall: Computer modelling comparing bipolar and unipolar modes. International Journal of Hyperthermia. 30(6):372-384. https://doi.org/10.3109/02656736.2014.949878S372384306SIVAGANGABALAN, G., BARRY, M. A., HUANG, K., LU, J., POULIOPOULOS, J., THOMAS, S. P., … KOVOOR, P. (2010). Bipolar Ablation of the Interventricular Septum is More Efficient at Creating a Transmural Line than Sequential Unipolar Ablation. Pacing and Clinical Electrophysiology, 33(1), 16-26. doi:10.1111/j.1540-8159.2009.02602.xNagashima, K., Watanabe, I., Okumura, Y., Ohkubo, K., Kofune, M., Ohya, T., … Hirayama, A. (2011). Lesion Formation by Ventricular Septal Ablation With Irrigated Electrodes. Circulation Journal, 75(3), 565-570. doi:10.1253/circj.cj-10-0870D’ Avila, A., Houghtaling, C., Gutierrez, P., Vragovic, O., Ruskin, J. N., Josephson, M. E., & Reddy, V. Y. (2004). Catheter Ablation of Ventricular Epicardial Tissue. Circulation, 109(19), 2363-2369. doi:10.1161/01.cir.0000128039.87485.0bDukkipati, S. R., d’ Avila, A., Soejima, K., Bala, R., Inada, K., Singh, S., … Reddy, V. Y. (2011). Long-Term Outcomes of Combined Epicardial and Endocardial Ablation of Monomorphic Ventricular Tachycardia Related to Hypertrophic Cardiomyopathy. Circulation: Arrhythmia and Electrophysiology, 4(2), 185-194. doi:10.1161/circep.110.957290Sosa, E., Scanavacca, M., d’ Avila, A., Oliveira, F., & Ramires, J. A. F. (2000). Nonsurgical transthoracic epicardial catheter ablation to treat recurrent ventricular tachycardia occurring late after myocardial infarction. Journal of the American College of Cardiology, 35(6), 1442-1449. doi:10.1016/s0735-1097(00)00606-9Nagashima, K., Watanabe, I., Okumura, Y., Sonoda, K., Kofune, M., Mano, H., … Hirayama, A. (2012). Epicardial Ablation With Irrigated Electrodes. Circulation Journal, 76(2), 322-327. doi:10.1253/circj.cj-11-0984Berjano, E. J. (2006). BioMedical Engineering OnLine, 5(1), 24. doi:10.1186/1475-925x-5-24Abraham, J. P., & Sparrow, E. M. (2007). A thermal-ablation bioheat model including liquid-to-vapor phase change, pressure- and necrosis-dependent perfusion, and moisture-dependent properties. International Journal of Heat and Mass Transfer, 50(13-14), 2537-2544. doi:10.1016/j.ijheatmasstransfer.2006.11.045Jo, B., & Aksan, A. (2010). Prediction of the extent of thermal damage in the cornea during conductive keratoplasty. Journal of Thermal Biology, 35(4), 167-174. doi:10.1016/j.jtherbio.2010.02.004HAINES, D. E., & WATSON, D. D. (1989). 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Journal of Interventional Cardiac Electrophysiology, 38(1), 35-42. doi:10.1007/s10840-013-9799-1Schutt, D., Berjano, E. J., & Haemmerich, D. (2009). Effect of electrode thermal conductivity in cardiac radiofrequency catheter ablation: A computational modeling study. International Journal of Hyperthermia, 25(2), 99-107. doi:10.1080/02656730802563051Gopalakrishnan, J. (2002). A Mathematical Model for Irrigated Epicardial Radiofrequency Ablation. Annals of Biomedical Engineering, 30(7), 884-893. doi:10.1114/1.1507845Suárez, A. G., Hornero, F., & Berjano, E. J. (2010). Mathematical Modeling of Epicardial RF Ablation of Atrial Tissue with Overlying Epicardial Fat. The Open Biomedical Engineering Journal, 4(1), 47-55. doi:10.2174/1874120701004020047Haemmerich, D., Chachati, L., Wright, A. S., Mahvi, D. M., Lee, F. T., & Webster, J. G. (2003). Hepatic radiofrequency ablation with internally cooled probes: effect of coolant temperature on lesion size. 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    2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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    2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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    withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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