RESUMEN
Numerical simulation is growing in its importance toward the design, testing and evaluation of medical devices. Computational fluid dynamics and finite element analysis allow improved calculation of stress, heat transfer, and flow to better understand the medical device environment. Current research focuses not only on improving medical devices, but also on improving the computational tools themselves. As methods and computer technology allow for faster simulation times, iterations and trials can be performed faster to collect more data. Given the adverse events associated with long-term inferior vena cava (IVC) filter placement, IVC filter design and device evaluation are of paramount importance. This work reviews computational methods used to develop, test, and improve IVC filters to ultimately serve the needs of the patient.
Asunto(s)
Filtros de Vena Cava , Simulación por Computador , Remoción de Dispositivos , Humanos , Hidrodinámica , Vena Cava InferiorRESUMEN
Arsenic, a human carcinogen that is associated with an increased risk of bladder cancer, is commonly found in drinking water. An important mechanism by which arsenic is thought to be carcinogenic is through the induction of epigenetic changes that lead to aberrant gene expression. Previously, we reported that the SAS2 gene is required for optimal growth of yeast in the presence of arsenite (As(III)). Yeast Sas2p is orthologous to human MYST1, a histone 4 lysine 16 (H4K16) acetyltransferase. Here, we show that H4K16 acetylation is necessary for the resistance of yeast to As(III) through the modulation of chromatin state. We further explored the role of MYST1 and H4K16 acetylation in arsenic toxicity and carcinogenesis in human bladder epithelial cells. The expression of MYST1 was knocked down in UROtsa cells, a model of bladder epithelium that has been used to study arsenic-induced carcinogenesis. Silencing of MYST1 reduced acetylation of H4K16 and induced sensitivity to As(III) and to its more toxic metabolite monomethylarsonous acid (MMA(III)) at doses relevant to high environmental human exposures. In addition, both As(III) and MMA(III) treatments decreased global H4K16 acetylation levels in a dose- and time-dependent manner. This indicates that acetylated H4K16 is required for resistance to arsenic and that a reduction in its levels as a consequence of arsenic exposure may contribute to toxicity in UROtsa cells. Based on these findings, we propose a novel role for the MYST1 gene in human sensitivity to arsenic.
Asunto(s)
Arsenicales , Histona Acetiltransferasas/metabolismo , Acetilación , Western Blotting , Cromatina/fisiología , Colorantes , Relación Dosis-Respuesta a Droga , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Silenciador del Gen/efectos de los fármacos , Histona Acetiltransferasas/fisiología , Humanos , Espectrometría de Masas , Retroviridae/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/crecimiento & desarrollo , Sales de Tetrazolio , Tiazoles , Vejiga Urinaria/citología , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/metabolismoRESUMEN
We assessed the short-term outcome of percutaneous coronary ultrasound thrombolysis (CUT) for high-risk thrombus-containing lesions in native coronaries in the setting of acute coronary syndromes (ACS). Data were prospectively collected in a multicenter (n = 32) registry of consecutive ACS patients. The study population (n = 126) had mostly (84%) totally occluded vessels. The mean age of clot was 5.7 +/- 9.5 days (range, 0-60 days). CUT (41 kHz, 18 W) led to device success in 112 (89%) patients, with a residual stenosis of 69% +/- 20%. Adjunct PTCA or stenting was used in 97% of the patients. Procedural success was achieved in 124 (98%) patients, with a final residual stenosis of 6% +/- 10%. There were no major adverse clinical events during hospitalization. Ultrasound thrombolysis is a feasible procedure that offers a safe and probably effective adjuvant device solution for the treatment of high-risk, thrombus-containing lesions in the native coronary arteries.