Theoretical analysis of the structural and chemical reactivity properties of the schistosomicidal drug niridazole

A theoretical quantum mechanical analysis of the structural, conformational and reactivity properties of the schistosomicidal drug niridazole is presented. The computations are carried out in the CNDO/2 approximation including full molecular geometry optimization and modellization of the solvent effect. The change in molecular properties when the molecule approaches a macromolecular receptor is simulated with decreasing values for the dielectric constant of the medium. In addition, the reactivity properties of niridazole are analyzed within the frontier orbital approximation. The structural analysis of the optimized geometries reveals a planar structure for the nitro group and the thiazole ring whereas the imidazolidinone ring is found to be non planar. The conformational analysis shows that the flexibility of the molecule, measured by the barriers to rotation of the imidazolidinone ring against the thiazole ring, increases greatly when the molecule approaches to a macromolecular receptor. Our reactivity results are in agreement with the experimental data and they support the hypothesis that the metabolic activation of niridazole in the schistosome involves a nucleophilic attack. The nitro group and some selected positions on the thiazole ring are the preferred points for this attack

Picosecond spectroscopy of electronically excited singlet states in biphenylene

A photophys. properties of biphenylene-h8 and biphenylene-d8 in soln. at room temp. was investigated with picosecond absorption and fluorescence spectroscopy. The weak fluorescence with complex vibrational structure originates entirely from the S1 state. It decays monoexponentially with a lifetime of 240 +- 20 ps. Upon photoexcitation to S2 no emission attributable to the S2 state was obsd. Lifetime and quantum yield of fluorescence (FF = 2.3 * 10-4) are the same for biphenylene-h8 and for the completely deuterated compd., indicating the C-H vibrations are not involved in the major radiationless decay process of the S1 level, i.e. internal conversion (jIC > 0.99). This conclusion is supported by INDO/S CI calcns. where strong changes of the CC bond orders (particularly in the central C4 ring) with S0 -> S1 excitation are found. The time-resolved excited-state absorption, measured at several wavelengths, decays biexponentially with time consts. of 8 +- 3 and 250 +- 40 ps. Various interpretations of the 8 ps lifetime are discussed; the conclusion results that the 8 ps transient has to be assigned to the lifetime of the S2 state even though the emission expected for an allowed transition with such a long lifetime is not obsd. Strong S1 -> Sn and S2 -> Sn excited-state absorption is found as predicted by INDO/S calcns

Outcomes of heart transplantation based on recipient's clinical profile: 21-year experience

Introducción: El trasplante cardíaco continúa siendo el tratamiento de elección en pacientes con miocardiopatías graves sin otras opciones terapéuticas. Los resultados alentadores del trasplante cardíaco en términos de supervivencia han permitido ampliar los criterios de selección del receptor, lo que ha llevado a la inclusión de pacientes de mayor complejidad en lista de espera. Objetivo: Analizar los resultados del trasplante cardíaco del Hospital Universitario Fundación Favaloro a lo largo de 21 años de seguimiento. Material y métodos: Entre febrero de 1993 y diciembre de 2014 se realizaron 442 trasplantes cardíacos ortotópicos en un único centro. Se analizaron en forma retrospectiva las historias clínicas de los pacientes, excluyéndose los pediátricos y protegiendo la confidencialidad de los datos. Para el análisis se dividió la serie en período 1 (febrero 1993 - agosto 2003) y período 2 (septiembre 2003 - diciembre 2014). Resultados: Se observó durante el segundo período una prevalencia mayor de candidatos con miocardiopatía dilatada no coronaria versus coronaria y un incremento significativo de la indicación de trasplante cardíaco en la miocardiopatía dilatada chagásica. La prevalencia de hipertensión pulmonar aumentó, realizándose un número mayor de trasplantes cardíacos en condición de emergencia, con requerimiento de inotrópicos y soporte circulatorio mecánico con balón de contrapulsación intraaórtico. Conclusiones: Se han observado cambios en el perfil clínico de los receptores de trasplante cardíaco, ingresando en lista de espera pacientes con un número mayor de comorbilidades. La cuidadosa elección de candidatos a trasplante requiere una revisión continua y un análisis individualizado de los diferentes factores que determinan la supervivencia de los pacientes y su impacto en los resultados de los programas de trasplante.Background: Heart transplantation is still the treatment of choice in patients with severe cardiomyopathies that do not have any therapeutic options. The promising results of heart transplantation in terms of survival have modified the criteria of recipients’ selection, including more complex patients on the waiting list. Objective: The aim of this report is to analyze the outcomes of heart transplantation performed at the Hospital Universitario Fundación Favaloro after 21 years of follow-up. Methods: Between February 1993 and December 2014, 442 orthotopic heart transplantations were performed at a single center. The clinical records of the recipients, excluding pediatric patients, were retrospectively analyzed, ensuring the confidentiality of the information. Two periods were considered: period 1 (from February 1993 to August 2003) and period 2 (from September 2003 to December 2014). Results: During the second period, the prevalence of recipients with non ischemic versus ischemic dilated cardiomyopathy was higher, and the indication of heart transplantation in Chagas dilated cardiomyopathy showed a significant increase. The prevalence of pulmonary hypertension increased and more emergency heart transplantations were performed, with requirements of inotropic agents and mechanical circulatory support with intraaortic balloon pump. Conclusions: The clinical profile of heart transplantation recipients has changed and more patients on the waiting list have a greater number of comorbidities. The careful selection of candidates for transplantation needs continuous revision and an individual analysis of the different factors that determine patients’ survival and its impact on the outcomes of transplantation programs.Fil: Peradejordi Lastras, Margarita Ana. Universidad Favaloro; ArgentinaFil: Favaloro, Liliana Ethel. Universidad Favaloro; ArgentinaFil: Vigliano, Carlos. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Renedo, María F.. Universidad Favaloro; ArgentinaFil: Martínez, Liliana. Universidad Favaloro; ArgentinaFil: Moscoloni, Silvia E.. Universidad Favaloro; ArgentinaFil: Abud, José. Universidad Favaloro; ArgentinaFil: Absi, Daniel O.. Universidad Favaloro; ArgentinaFil: Favaloro, Roberto René. Universidad Favaloro; ArgentinaFil: Bertolotti, Alejandro Mario. Universidad Favaloro; Argentin