Estudio galénico de los medicamentos utilizados en España para el tratamiento del Glaucoma

La presión intraocular elevada es el principal factor de riesgo implicado en el desarrollo del glaucoma, segunda causa de ceguera irreversible a nivel mundial según la OMS. Este hecho hace que la principal diana farmacoterapéutica en el tratamiento de esta enfermedadsea la reducción de la PIO. Para ello, la estrategia farmacológica principal consiste en la administración de agentes hipotensores por diferentes vías de administración. En el presente trabajo se realiza una recopilación sobre las posibilidades existentes en el mercado español de los diferentes fármacos y especialidades farmacéuticas a disposición del profesional sanitario a la hora de abordar el tratamiento del glaucoma.Además, se han analizado las diferentes formulaciones de losmedicamentos recogidos en la Agencia Española de Medicamentos y Productos Sanitarios, para extraer información práctica que pudiera ser aplicable al diseño y elaboración de unmedicamento de uso oftálmico para el tratamiento de esta enfermedad. Nos hemos centrado sobre todo en el apartado referente a los excipientes (vehículo, isotonizantes, viscosizantes, sistema tampón, conservantes, antioxidantes y solubilizantes),que van a determinar la estabilidad del principio activo formulado, tolerancia ocular y respuesta terapéutica. Los resultados obtenidos se presentan en formade tablas, que posteriormente han sido analizados para extraer conclusiones respecto a diferentes aspectos: tipo de forma farmacéutica, sistemas unidosis o multidosis, empleo o no de conservantes y viscosizantes, etc. Los resultados muestran que el medicamento tipo sería un colirio en solución con uno o dos principios activos, multidosis, con cloruro de benzalconio como conservante, NaCl como isotonizante, tampón fosfato, sin viscosizante específico y aceite de ricino polioxietilenado como solubilizante,si fuera necesarioUniversidad de Sevilla. Doble grado en Farmacia y Óptica y Optometrí

Conferencia de consenso: tratamiento de la diabetes tipo 2 en el paciente anciano

El tratamiento de la diabetes tipo 2 en el anciano representa un importante reto tanto desde el punto de vista clínico como del de la salud pública. El envejecimiento poblacional está condicionando un marcado incremento de la pandemia de diabetes en las personas de edad avanzada. Sin embargo, existen pocas evidencias científicas que apoyen el tratamiento más adecuado de la diabetes en los ancianos. Dada la gran heterogeneidad de la población anciana, que incluye a sujetos con muy diferente capacidad funcional y cognitiva, diversa comorbilidad y con muy diferente expectativa de vida, resulta crucial realizar una valoración global del anciano desde una perspectiva biopsicosocial y abordar integralmente los factores de riesgo vascular, planteando unos objetivos personalizados de control glucémico. En ancianos frágiles o con corta expectativa de vida puede ser razonable mantener un objetivo de HbA1c de 7,6-8,5%. La estrategia terapéutica en el anciano con diabetes tipo 2 debe individualizarse y consensuarse con el paciente y sus cuidadores, en función del objetivo planteado. Mejorar la calidad de vida, preservar la seguridad del paciente y evitar los efectos adversos del tratamiento antidiabético deben ser objetivos básicos. Dada la mayor predisposición de los ancianos a las hipoglucemias y sus graves consecuencias en esta población, deberían priorizarse las terapias antidiabéticas que minimicen el riesgo de episodios hipoglucémicos

Análisis de materias de especialización de comunidades científicas mediante redes complejas

En este trabajo se intenta asignar palabras clave (keywords) a una comunidad de autores de trabajos científicos de tal forma que éstas sean representativas de su comunidad. Para ello partiremos de una red de coautoría de artículos y proyectos y las keywords individuales de cada autor. Planteamos dos algoritmos basados en la técnica de "propagación de etiquetas" (label propagation) y diseñamos varias métricas auxiliares para tratar de evaluar la calidad de éstos. Concluimos que uno de los dos algoritmos ofrece mejores resultados que una asignación de keywords sin propagar etiquetas.<br /

Patients' and physicians' preferences for type 2 diabetes mellitus treatments in Spain and Portugal: a discrete choice experiment

Objective To assess Spanish and Portuguese patients’ and physicians’ preferences regarding type 2 diabetes mellitus (T2DM) treatments and the monthly willingness to pay (WTP) to gain benefits or avoid side effects. Methods An observational, multicenter, exploratory study focused on routine clinical practice in Spain and Portugal. Physicians were recruited from multiple hospitals and outpatient clinics, while patients were recruited from eleven centers operating in the public health care system in different autonomous communities in Spain and Portugal. Preferences were measured via a discrete choice experiment by rating multiple T2DM medication attributes. Data were analyzed using the conditional logit model. Results Three-hundred and thirty (n=330) patients (49.7% female; mean age 62.4 [SD: 10.3] years, mean T2DM duration 13.9 [8.2] years, mean body mass index 32.5 [6.8] kg/m2, 41.8% received oral + injected medication, 40.3% received oral, and 17.6% injected treatments) and 221 physicians from Spain and Portugal (62% female; mean age 41.9 [SD: 10.5] years, 33.5% endocrinologists, 66.5% primary-care doctors) participated. Patients valued avoiding a gain in bodyweight of 3 kg/6 months (WTP: €68.14 [95% confidence interval: 54.55–85.08]) the most, followed by avoiding one hypoglycemic event/month (WTP: €54.80 [23.29–82.26]). Physicians valued avoiding one hypoglycemia/week (WTP: €287.18 [95% confidence interval: 160.31–1,387.21]) the most, followed by avoiding a 3 kg/6 months gain in bodyweight and decreasing cardiovascular risk (WTP: €166.87 [88.63–843.09] and €154.30 [98.13–434.19], respectively). Physicians and patients were willing to pay €125.92 (73.30–622.75) and €24.28 (18.41–30.31), respectively, to avoid a 1% increase in glycated hemoglobin, and €143.30 (73.39–543.62) and €42.74 (23.89–61.77) to avoid nausea. Conclusion Both patients and physicians in Spain and Portugal are willing to pay for the health benefits associated with improved diabetes treatment, the most important being to avoid hypoglycemia and gaining weight. Decreased cardiovascular risk and weight reduction became the third most valued attributes for physicians and patients, respectively

The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells

The MAX network transcriptional repressor (MNT) is an MXD family transcription factor of the basic helix-loop-helix (bHLH) family. MNT dimerizes with another transcriptional regulator, MYC-associated factor X (MAX), and down-regulates genes by binding to E-boxes. MAX also dimerizes with MYC, an oncogenic bHLH transcription factor. Upon E-box binding, the MYC-MAX dimer activates gene expression. MNT also binds to the MAX dimerization protein MLX (MLX), and MNT-MLX and MNT-MAX dimers co-exist. However, all MNT functions have been attributed to MNT-MAX dimers, and no functions of the MNT-MLX dimer have been described. MNT's biological role has been linked to its function as a MYC oncogene modulator, but little is known about its regulation. We show here that MNT localizes to the nucleus of MAX-expressing cells and that MNT-MAX dimers bind and repress the MNT promoter, an effect that depends on one of the two E-boxes on this promoter. In MAX-deficient cells, MNT was overexpressed and redistributed to the cytoplasm. Interestingly, MNT was required for cell proliferation even in the absence of MAX. We show that in MAX-deficient cells, MNT binds to MLX, but also forms homodimers. RNA-sequencing experiments revealed that MNT regulates the expression of several genes even in the absence of MAX, with many of these genes being involved in cell cycle regulation and DNA repair. Of note, MNT-MNT homodimers regulated the transcription of some genes involved in cell proliferation. The tight regulation of MNT and its functionality even without MAX suggest a major role for MNT in cell proliferation.This work was supported by Grant SAF2017-88026-R from Agencia Estatal de Investigación, Spanish Government (to J. L. and M. D. D.), funded in part by FEDER Program from the European Union, National Institutes of Health Grant CA57138/CA from NCI (to R. N. E.), and grants from Shriners Hospitals for Children (to P. J. H.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health

Sin3b interacts with Myc and decreases Myc levels

Myc expression is deregulated in many human cancers. A yeast two-hybrid screen has revealed that the transcriptional repressor Sin3b interacts with Myc protein. Endogenous Myc and Sin3b co-localize and interact in the nuclei of human and rat cells, as assessed by co-immunoprecipitation, immunofluorescence, and proximity ligation assay. The interaction is Max-independent. A conserved Myc region (amino acids 186-203) is required for the interaction with Sin3 proteins. Histone deacetylase 1 is recruited to Myc-Sin3b complexes, and its deacetylase activity is required for the effects of Sin3b on Myc. Myc and Sin3a/b co-occupied many sites on the chromatin of human leukemia cells, although the presence of Sin3 was not associated with gene down-regulation. In leukemia cells and fibroblasts, Sin3b silencing led to Myc up-regulation, whereas Sin3b overexpression induced Myc deacetylation and degradation. An analysis of Sin3b expression in breast tumors revealed an association between low Sin3b expression and disease progression. The data suggest that Sin3b decreases Myc protein levels upon Myc deacetylation. As Sin3b is also required for transcriptional repression by Mxd-Max complexes, our results suggest that, at least in some cell types, Sin3b limits Myc activity through two complementary activities: Mxd-dependent gene repression and reduction of Myc levels

p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes

It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes

Osteoporosis secundarias

Se denomina osteoporosis secundaria a aquella que es causada por patologías o medicaciones, distintas a la pérdida ósea explicable por la etapa postmenopáusica o envejecimiento. Las posibles patologías que pueden condicionar la pérdida de masa ósea son muy variadas: endocrinológicas, digestivas, genéticas, hematológicas, reumáticas, post-transplante, farmacológicas y un amplio grupo misceláneo. En el artículo se revisan esencialmente las causas endocrinológicas, con especial énfasis en los aspectos más controvertidos en la actualidad, seguidos de una aproximación clínica para el diagnóstico sistemático de estas patologías, frecuentes en los casos etiquetados inicialmente de osteoporosis primaria