Adherencia al tratamiento con fármacos moduladores de la enfermedad sintéticos en la artritis reumatoide. Resultados del estudio OBSERVAR

[Abstract] Background: Treatment compliance with disease-modifying antirheumatic drugs (DMARD) is essential to achieve the therapeutic goals in rheumatoid arthritis (RA). However, despite the need for good compliance, there is evidence that patients with RA frequently fail to use DMARD for the control of RA. Thus, the main objective of the OBSERVAR study is to evaluate the reasons for the lack of therapeutic adherence to synthetic DMARD in these patients. Patients and methods: A Delphi process involving 18 randomly selected Spanish rheumatologists determined the level of agreement with 66 causes of noncompliance selected from the literature in relation to synthetic DMARD in RA. Results: The reasons for noncompliance were consistent in 75.7%, although 3 reasons (4.5%) were highly consistent: 1) not knowing what to do in the case of an adverse event with DMARD; 2) not having undergone adherence screening by health personnel for early detection of "noncompliant patients"; and 3) not having undergone interventions or strategies that improve adherence. Conclusion: In order to improve adherence to RA treatment with synthetic DMARD, the patient should be adequately informed of each new treatment introduced, the patient's compliance profile should be incorporated into the clinical routine and the patient's motivation for therapeutic compliance be reinforced through the methods available to us.[Resumen] Introducción. La cumplimentación del tratamiento modificador de la enfermedad es esencial para alcanzar los objetivos terapéuticos en la artritis reumatoide (AR). Sin embargo, y a pesar de la necesidad de una buena adherencia, existe evidencia de que muchos pacientes con AR no cumplen adecuadamente con la prescripción del tratamiento indicado con fármacos moduladores de la enfermedad de acción lenta (FAME) sintéticos o convencionales. Conscientes de la importancia de este hecho, el estudio sobre observancia terapéutica en AR (estudio OBSERVAR) tiene como objetivo principal valorar los motivos de la falta de adherencia terapéutica a los FAME sintéticos en estos pacientes. Pacientes y métodos. Mediante un proceso Delphi entre 18 reumatólogos españoles seleccionados aleatoriamente se determinó el grado de acuerdo con 66 causas de incumplimiento seleccionadas de la bibliografía, en relación con los FAME sintéticos en la AR. Resultados. Los motivos de incumplimiento fueron consistentes en el 75,7%, si bien 3 razones (4,5%) destacaron como muy consistentes: 1) desconocer qué hacer cuando se sufre un acontecimiento adverso con el FAME; 2) no llevar a cabo métodos de cribado de la adherencia por el personal sanitario para detectar a los «pacientes incumplidores» de forma temprana y 3) no aplicar intervenciones o estrategias que mejoren la adherencia terapéutica. Conclusión. Para mejorar la adherencia al tratamiento de la AR con FAME sintéticos se debe informar al paciente de cada tratamiento nuevo introducido, incorporar el perfil de cumplimiento del paciente en la rutina clínica, y reforzar la motivación del paciente al cumplimiento terapéutico mediante los métodos a nuestro alcance

UV-induced degradation of securin is mediated by SKP1-CUL1-βTrCP E3 ubiquitin ligase

Securin is a chaperone protein with bifunctional properties. It binds to separase to inhibit premature sister chromatid separation until the onset of anaphase, and it also takes part in cell-cycle arrest after UV irradiation. At metaphase-to-anaphase transition, securin is targeted for proteasomal destruction by the anaphase-promoting complex or cyclosome (APC/C), allowing activation of separase. However, although securin is reported to undergo proteasome-dependent degradation after UV irradiation, the ubiquitin ligase responsible for securing ubiquitylation has not been well characterized. In this study, we show that UV radiation induced a marked reduction of securin in both the nucleus and cytoplasm. Moreover, we show that GSK-3β inhibitors prevent securin degradation, and that CUL1 and βTrCP are involved in this depletion. We also confirmed that SKP1-CUL1-βTrCP (SCFβTrCP) ubiquitylates securin in vivo, and identified a conserved and unconventional βTrCP recognition motif (DDAYPE) in the securin primary amino acid sequence of humans, nonhuman primates and rodents. Furthermore, downregulation of βTrCP caused an accumulation of securin in non-irradiated cells. We conclude that SCFβTrCP is the E3 ubiquitin ligase responsible for securing degradation after UV irradiation, and that it is involved in securin turnover in nonstressed cells.Ministerio de Educación y Ciencia SAF 2005-07713-C03-0

IAA : Información y actualidad astronómica (29)

Sumario : Sunrise, una aventura polar.-- Nuestra tormentosa estrella.-- ¿Son válidos los modelos de atmósferas estelares?.-- ¿Viajaremos más rápido que la luz?.-- HISTORIAS DE ASTRONOMÍA. Últimas tardes con Hipatia.-- DECONSTRUCCIÓN Y otros ENSAYOS. Edwin Hubble.-- EL “MOBY DICK” DE... Antxon Alberdi (IAA-CSIC).-- ACTUALIDAD.-- Betelgeuse en ebullición.-- ¿Qué supone el hallazgo de glicina en el cometa 81P/Wild?.-- ¿Existe el cinturón de Gould?.-- Cosmología de alta precisión con supernovas.-- Púlsares silenciosos en radio pero ruidosos en rayos gamma.-- El Quinteto de Stéphan.-- Ecos gravitatorios del Universo primordial.-- Júpiter castigado.-- ENTRE BASTIDORES.-- CIENCIA: PILARES E INCERTIDUMBRES : Formación de estrellas masivas.N

Lack Of Association Between Nutritional Status And Change In Clinical Category Among Hiv-infected Children In Brazil.

Malnutrition is common among HIV-infected children. Our objective was to study the occurrence of malnutrition and its relationship with changes in clinical category among HIV-infected children. Longitudinal study, at the Pediatrics Department and Pediatrics Investigation Center (CIPED), Faculdade de Ciências Médicas da Universidade Estadual de Campinas (Unicamp). We reviewed the hospital records of 127 vertically HIV-infected children. Anthropometric measurements were obtained at the beginning of follow-up, at clinical category change and five months later. These were converted to z-scores of weight/age, height/age and weight/height. Data were presented as means, standard deviations, frequency counts and percentages. The Wilcoxon and Kruskal-Wallis tests and odds ratios were used in the analysis. We found that 51 (40.2%) were undernourished and 40 (31.5%) were stunted, with higher risk of being included in clinical category C. There was an association between nutritional condition and the clinical categories of the Centers for Disease Control classification (1994), and with age at symptom onset (except for height z-score). During follow-up, 36 patients (28.4%) changed their clinical category, which occurred early among the undernourished patients. The group that changed its clinical category maintained the same z-score distribution for weight, height and weight/height throughout follow-up. Aids manifestation severity was associated with nutritional status and with age at symptom onset, but change in clinical category was not followed by worsening of nutritional status.12362-