Análogos fluorescentes de fármacos lipídicos con actividad antiparasitaria y antineoplásica. Diseño, síntesis y aplicaciones

Tesis leída en la Facultad de Ciencias Químicas en octubre de 2009.La emisión de fluorescencia en fase condensada es un proceso de origen electrónico, lo que ha retrasado históricamente su comprensión, a pesar de que las primeras observaciones del fenómeno se realizaron en Sevilla ya en el siglo XVI.1 Hoy en día se sabe que las molécula excitadas electrónicamente por absorción fotónica permanecen nanosegundos en dicho estado excitado, un tiempo que es ~ 106 veces mayor que el requerido para la excitación. En la mayoría de los casos, la molécula pierde este exceso de energía electrónica a través de procesos no radiantes. Sin embargo, para un número reducido de compuestos la probabilidad de la emisión es mayor que la de los procesos no radiantes y, por tanto, se produce emisión de fluorescencia. Como era de esperar, se ha dedicado un gran esfuerzo investigador a lo largo de casi un siglo para determinar los factores electrónicos y estructurales que optimizan las propiedades emisivas de una molécula; sin embargo, todavía hoy el diseño de nuevos grupos fluorescentes (fluoróforos) se lleva a cabo de forma semi-empírica. En contraste, el desarrollo de las técnicas instrumentales para la excitación y detección de fluorescencia ha progresado considerablemente.Peer reviewe

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)