Quercetin and its metabolites inhibit the membrane NADPH oxidase activity in vascular smooth muscle cells from normotensive and spontaneously hypertensive rats.

Quercetin, the most abundant dietary flavonol, exerts antioxidant effects reducing vascular superoxide (O2(-)) and improving endothelial function in animal models of cardiovascular disease. Herein we evaluated the effects of quercetin, and its plasma metabolites, on the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase activity, the main source of O2(-) in the vessel wall, in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Quercetin and its metabolites isorhamnetin and kaempferol inhibited the NADPH-stimulated lucigenin-chemiluminescence signal in VSMCs from both strains. The inhibitory effect of quercetin-3-glucuronide increased after prolonged incubation and was inhibited in the presence of the ß-glucuronidase inhibitor saccharolactone. These effects were unrelated to their O2(-) scavenging properties, since they induced only a small inhibition of the rate of pyrogallol autoxidation at high concentrations. All bioflavonoids tested acted as non-competitive inhibitors with respect to NADPH. In conclusion, quercetin and its metabolites inhibit the NADPH oxidase activity in VSMCs reducing O2(-) generation more efficiently than their effect as O2(-) scavengers. The effect of quercetin-3-glucuronide was due to deconjugation and release of free quercetin. The effect is similar in VSMCs from normotensive and hypertensive animals.

[Boceprevir and telaprevir safety in routine clinical practice]. / Seguridad de boceprevir y telaprevir en la práctica clínica habitual.

PURPOSE: To compare the safety profile of telaprevir (TLV) and boceprevir (BOC) with each other and with those described in clinical trials (CT). MATERIAL AND METHODS: Retrospective multicenter observational study. Variables collected: age, sex, type of patient (naive, nonresponder or recurrent), fibroscan, Hb nadir, neutrophil and platelet count, presence of rash, anorectal discomfort, number of patients treated with erythropoiesis stimulating factors (EPO) and colony stimulating factors granulocyte (G-CSF). RESULTS: BOC vs CT: anemia (56.5% vs. 49%.), Thrombocytopenia (56.5% vs 32%, p = 0.023). neutropenia (17.4% vs. 29.5%). Use of EPO (13% vs 43%;. p = 0.008), pruritus (13% vs. 21.1%), rash (16.1% vs. 8.7%), anorectal discomfort (4.3% vs. 0%, p = 0.0001), dysgeusia (47.8% vs. 37%). TLV vs. CT: anemia (51.2% vs. 32%, p = 0.014), neutropenia (2.3 vs 3.6%), thrombocytopenia (41.9% vs. 27.4%, p = 0.05), pruritus (39.5% vs 47), rash (16.3% vs 55%, P <0.001), anorectal discomfort (39.5% vs 26%), dysgeusia (14% vs. 9.5%). BOC vs TLV: anemia (56.5% vs 51.2%), neutropenia (17.4% vs 2.3%), thrombocytopenia (56.5% vs 41.9%), rash (8.7% vs 16.3%), pruritus (39.5% vs 13%) and anorectal discomfort (4.3% vs 39.5%, P = 0.006), dysgeusia (14% vs 47.8%, P = 0.007), EPO (13% vs. 25.6%). GCSF was used for a patient treated with TLV. CONCLUSIONS: 1. BOC and TLV have shown a worse safety profile for anemia, thrombocytopenia and anorectal discomfort than those described in CT. 2. As in CT, anemia, neutropenia and thrombocytopenia were more common with BOC. Patients treated with TLV experienced more pruritus, rash and anorectal discomfort.

Seguridad de boceprevir y telaprevir en la práctica clínica habitual / Boceprevir and telaprevir safety in routine clinical practice

Objetivo: Comparar el perfil de seguridad telaprevir (TLV) y boceprevir (BOC) entre sí y con lo descrito en ensayos clínicos (EECC).Material y método: Estudio multicéntrico observacional retrospectivo. Variables recogidas: edad, sexo, tipo de paciente (naïve, no respondedor o recidivantes), fibroscan, Hb nadir, recuento de neutrófilos y plaquetas, presencia de exantema, malestar anorrectal, número de pacientes tratados con estimuladores de la eritropoyesis (EPO) y factores estimuladores de colonias de granulocitos (G-CSF).Resultados: BOC vs EECC: anemia (56,5% vs. 49%), trombocitopenia (56,5% vs. 32%; p = 0,023). Neutropenia (17,4% vs. 29,5%).Utilización de EPO (13% vs. 43%; p = 0,008), prurito (13% vs.21,1%), exantema (8,7% vs. 16,1%); molestias anorrectales (4,3%vs. 0%; p = 0,0001), disgeusia (47,8% vs. 37%). TLV vs. EECC: anemia (51,2% vs. 32%; p = 0,014), neutropenia (2,3 vs. 3,6%), trombocitopenia (41,9% vs. 27,4%; p = 0,05), prurito (39,5 vs. 47%),exantema (16,3% vs. 55%; p < 0,001), molestias anorrectales(39,5% vs. 26%). Disgeusia (14% vs. 9,5%). BOC vs. TLV: anemia (56,5% vs. 51,2%), neutropenia (17,4% vs. 2,3%), trombocitopenia (56,5% vs. 41,9%), exantema (8,7% vs. 16,3%), prurito (39,5% vs. 13%) y molestias anorrectales (4,3% vs. 39,5%; p = 0,006), disgeusia (47,8% vs. 14%; p = 0,007) EPO (13% vs.25,6%). G-CSF se utilizó para un paciente tratado con TLV.Conclusiones:1. BOC y TLV han mostrado un perfil de seguridad peor que en los EECC en cuanto a anemia, trombocitopenia y malestar ano-rrectal.2. Al igual que en EECC, anemia, neutropenia y trombocitopenia fueron más frecuentes con BOC. Por otro lado los pacientes tratados con TLV presentaron más prurito, exantema y malestar anorrectal

Purpose: To compare the safety profile of telaprevir (TLV) and boceprevir (BOC) with each other and with those described in clinical trials (CT).Material and methods: Retrospective multicenter observational study. Variables collected: age, sex, type of patient (naive, non responder or recurrent), fibroscan, Hb nadir, neutrophil and platelet count, presence of rash, anorectal discomfort, number of patients treated with erythropoiesis stimulating factors (EPO) and colony stimulating factors granulocyte (G-CSF).Results: BOC vs CT: anemia (56.5% vs. 49%.), Thrombocytopenia(56.5% vs 32%, p = 0.023). neutropenia (17.4% vs. 29.5%). Use of EPO (13% vs 43%;. p = 0.008), pruritus (13% vs. 21.1%), rash(16.1% vs. 8.7%), anorectal discomfort (4.3% vs. 0%, p =0.0001), dysgeusia (47.8% vs. 37%). TLV vs. CT: anemia (51.2%vs. 32%, p = 0.014), neutropenia (2.3 vs 3.6%), thrombocytopenia (41.9% vs. 27.4%, p = 0.05), pruritus (39.5% vs 47), rash(16.3% vs 55%, P <0.001), anorectal discomfort (39.5% vs26%), dysgeusia (14% vs. 9.5%). BOC vs TLV: anemia (56.5% vs51.2%), neutropenia (17.4% vs 2.3%), thrombocytopenia(56.5% vs 41.9%), rash (8.7% vs 16.3%), pruritus (39.5% vs 13%) and anorectal discomfort (4.3% vs 39.5%, P = 0.006), dysgeusia (14% vs 47.8%, P = 0.007), EPO (13% vs. 25.6%). G-CSF was used for a patient treated with TLV.Conclusions:1. BOC and TLV have shown a worse safety profile for anemia, thrombocytopenia and anorectal discomfort than those described in CT.2. As in CT, anemia, neutropenia and thrombocytopenia were more common with BOC. Patients treated with TLV experienced more pruritus, rash and anorectal discomfort

Coordinación de asignaturas en el plan de estudios como actividad formativa del equipo docente multidisciplinar para la Licenciatura de Farmacia / Coordination of subjects in the program as a formative activity of the multidisciplinary educational team for the degree in Pharmacy

La Universidad de Granada, dentro del Plan Estratégico y el Contrato Programa 2007-2011 de lasUniversidades Públicas de Andalucía puso en marcha la convocatoria de apoyo a la formación delprofesorado principiante y mejora de la docencia por el Vicerrectorado para la Garantía de la Calidad(http://calidad.ugr.es/pages/secretariados/form_apoyo_calidad/apoyo_formacion_principiante/convocatoria). En el proyecto participan 15 profesores, 5 profesores experimentados y 10 profesores novelesde seis departamentos diferentes.. Entre los objetivos se incluye la optimización de la actividaddocente de profesorado principiante. En este sentido se estudió la situación en el nuevo plan de estudiode Grado en Farmacia de las asignaturas que dichos profesores impartimos, así como la relación entreellas y la posible existencia de solapamientos de contenidos docentes. Las fichas docentes muestranciertos solapamientos de competencias y carencias en algunos casos. Esto supuso una revisiónexhaustiva para llevar a cabo una correcta coordinación entre los profesores que le permita alalumnado un aprendizaje organizado y coherente(AU)

The University of Granada, inside the Strategic Plan and the Contract Program 2007-2011 of thePublic Universities of Andalusia started a public call to improve the formation of young lecturers andthe teaching activity(http://calidad.ugr.es/pages/secretariados/form_apoyo_calidad/apoyo_formacion_principiante/convocatoria). In the project there take part 15 lecturers, 5 experienced and 10 young lecturers from sixdifferent departments. Within the objectives it is included the optimisation of the teaching activity ofyoung lecturers. In this sense, it was studied the situation of the subjects that the above mentionedlecturers give within the new degree in Pharmacy, as well as the relation between they and the possibleexistence of any overlapping in the contents. The teaching contents showed the existence of certainoverlapping within competences and deficiencies in some cases. This supposed an exhaustive reviewto carry out the correct coordination between the different lecturers so that it will allow the organizedand coherent learning of the students(AU)