El síndrome facetar lumbar: Tratamiento mediante infiltraciones facetarias con fenol

Se presenta una serie de 125 pacientes afectos de cuadro de lumbociatalgia atípica, diagnosticados de síndrome facetario y tratados con infiltraciones de solución fenolada en las articulaciones interapofisarias posteriores afectadas, seguidas de un programa de rehabilitación protocolizado tras las infiltraciones. A propósito de los mismos y tras una análisis estadístico de los datos obtenidos del estudio, se establecen algunos criterios para el tratamiento de pacientes aquejados de este tipo de patología.The authors present a series of 125 patients afflicted with an atypical sciatic low-back pain, who were diagnosed of "facet joint syndrome" and treated with injections of phenol solution in the affected lumbar zygapophysial joints. The patients followed a protocolized rehabilitation program. After an statistical analysis of the data obtained from the study, some criteria are stabilized for the treatment of patients suffering this pathology

Enhanced nuclear protein export in premature aging and rescue of the progeria phenotype by modulation of CRM1 activity

The study of Hutchinson–Gilford progeria syndrome (HGPS) has provided important clues to decipher mechanisms underlying aging. Progerin, a mutant lamin A, disrupts nuclear envelope structure/function, with further impairment of multiple processes that culminate in senescence. Here, we demonstrate that the nuclear protein export pathway is exacerbated in HGPS, due to progerin‐driven overexpression of CRM1, thereby disturbing nucleocytoplasmic partitioning of CRM1‐target proteins. Enhanced nuclear export is central in HGPS, since pharmacological inhibition of CRM1 alleviates all aging hallmarks analyzed, including senescent cellular morphology, lamin B1 downregulation, loss of heterochromatin, nuclear morphology defects, and expanded nucleoli. Exogenous overexpression of CRM1 on the other hand recapitulates the HGPS cellular phenotype in normal fibroblasts. CRM1 levels/activity increases with age in fibroblasts from healthy donors, indicating that altered nuclear export is a common hallmark of pathological and physiological aging. Collectively, our findings provide novel insights into HGPS pathophysiology, identifying CRM1 as potential therapeutic target in HGPS

The molecular basis and biologic significance of the β-dystroglycan-emerin interaction

β-dystroglycan (β-DG) assembles with lamins A/C and B1 and emerin at the nuclear envelope (NE) to maintain proper nuclear architecture and function. To provide insight into the nuclear function of β-DG, we characterized the interaction between β-DG and emerin at the molecular level. Emerin is a major NE protein that regulates multiple nuclear processes and whose deficiency results in Emery–Dreifuss muscular dystrophy (EDMD). Using truncated variants of β-DG and emerin, via a series of in vitro and in vivo binding experiments and a tailored computational analysis, we determined that the β-DG–emerin interaction is mediated at least in part by their respective transmembrane domains (TM). Using surface plasmon resonance assays we showed that emerin binds to β-DG with high affinity (KD in the nanomolar range). Remarkably, the analysis of cells in which DG was knocked out demonstrated that loss of β-DG resulted in a decreased emerin stability and impairment of emerin-mediated processes. β-DG and emerin are reciprocally required for their optimal targeting within the NE, as shown by immunofluorescence, western blotting and immunoprecipitation assays using emerin variants with mutations in the TM domain and B-lymphocytes of a patient with EDMD. In summary, we demonstrated that β-DG plays a role as an emerin interacting partner modulating its stability and function

The intracellular domain of β-dystroglycan mediates the nucleolar stress response by suppressing UBF transcriptional activity

β-dystroglycan (β-DG) is a key component of multiprotein complexes in the plasma membrane and nuclear envelope. In addition, β-DG undergoes two successive proteolytic cleavages that result in the liberation of its intracellular domain (ICD) into the cytosol and nucleus. However, stimuli-inducing ICD cleavage and the physiological relevance of this proteolytic fragment are largely unknown. In this study we show for the first time that β-DG ICD is targeted to the nucleolus where it interacts with the nuclear proteins B23 and UBF (central factor of Pol I-mediated rRNA gene transcription) and binds to rDNA promoter regions. Interestingly DG silencing results in reduced B23 and UBF levels and aberrant nucleolar morphology. Furthermore, β-DG ICD cleavage is induced by different nucleolar stressors, including oxidative stress, acidosis, and UV irradiation, which implies its participation in the response to nucleolar stress. Consistent with this idea, overexpression of β-DG elicited mislocalization and decreased levels of UBF and suppression of rRNA expression, which in turn provoked altered ribosome profiling and decreased cell growth. Collectively our data reveal that β-DG ICD acts as negative regulator of rDNA transcription by impeding the transcriptional activity of UBF, as a part of the protective mechanism activated in response to nucleolar stress

RNA Foci Formation in a Retinal Glial Model for Spinocerebellar Ataxia Type 7

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder characterized by cerebellar ataxia and retinopathy. SCA7 is caused by a CAG expansion in the ATXN7 gene, which results in an extended polyglutamine (polyQ) tract in the encoded protein, the ataxin-7. PolyQ expanded ataxin-7 elicits neurodegeneration in cerebellar Purkinje cells, however, its impact on the SCA7-associated retinopathy remains to be addressed. Since Müller glial cells play an essential role in retinal homeostasis, we generate an inducible model for SCA7, based on the glial Müller MIO-M1 cell line. The SCA7 pathogenesis has been explained by a protein gain-of-function mechanism, however, the contribution of the mutant RNA to the disease cannot be excluded. In this direction, we found nuclear and cytoplasmic foci containing mutant RNA accompanied by subtle alternative splicing defects in MIO-M1 cells. RNA foci were also observed in cells from different lineages, including peripheral mononuclear leukocytes derived from SCA7 patient, suggesting that this molecular mark could be used as a blood biomarker for SCA7. Collectively, our data showed that our glial cell model exhibits the molecular features of SCA7, which makes it a suitable model to study the RNA toxicity mechanisms, as well as to explore therapeutic strategies aiming to alleviate glial dysfunction

Recomendaciones para la buena práctica de la medicina en anestesiología

At present, the Anesthesiology is recognized as a medical discipline and the activities of the anesthesiologist are wide, since it interferes in all the processes that happen during the anesthetic - surgical act. The most common reason of damages or serious complications they are associated with faults in the suitable ventilation of the patient. The aim of the present work is to generate specific and general recommendations directed to specialists of Anesthesiology, from the analysis of the complaints received in the CONAMED. There were analyzed all the complaints received for the specialty of anesthesiology from June, 1996 to May, 2001. Sociodemographic variables were included, information about institution of health and motive of complaint among others. There was included information of the Medical Integral Valuation, to obtain the type of used anesthesia. For the analysis descriptive statistics was used, for this intention it was used SPSS 10.1. Results: there was analyzed a whole of 97 complaints, 74.2 % of the complaints corresponded to the female sex, average of age 34.3 years, the major proportion of the complaints were to institutions of Social Security (67.0%). The proportion of malpractice for type of institution was of 75 % in the private roads, 57.4 % in Social Security and 52.6% in the Public Services. Problems identified with major frequency in the complaints with malpractice were in order: dural puncture, encephalopathy ischemic and cerebral irreversible damage and injury of nervous roots. Five deaths related with anesthesia were identified. The results obtained in the present work as for the problems in the practice of anesthesiology are very similar to the reported ones in the literature and a proportion of cases they can be prevenibles across a better training and supervision of the procedures that are realized.En la actualidad, la Anestesiología se reconoce como una disciplina médica y las actividades del anestesiólogo son amplias, ya que se involucra en todos los procesos que ocurren durante el acto anestésico-quirúrgico. La causa más común de daños o complicaciones serias están asociadas con fallas en la ventilación adecuada del paciente. El objetivo del presente trabajo es emitir recomendaciones generales y específicas, dirigidas a los especialistas de Anestesiología, a partir del análisis de las quejas recibidas en la CONAMED. Se analizaron todas las quejas recibidas en la CONAMED para la especialidad de anestesiología de junio de 1996 a mayo de 2001. Se incluyeron variables sociodemográficas, de la institución de salud y motivo de queja entre otras. Se incluyó información de la Valoración Médica Integral, para obtener el tipo de anestesia utilizada. Para el análisis se empleó estadística descriptiva, para este propósito se utilizó el paquete estadístico SPSS 10.1. Resultados: se analizaron un total de 97 quejas, 74.2% de las quejas correspondieron al sexo femenino, promedio de edad pacientes 34.3 años, la mayor proporción de las quejas correspondió a instituciones de Seguridad Social (67.0%). La proporción de mala práctica por tipo de institución fue de 75% en las privadas, 57.4% en seguridad social y 52.6% en servicios públicos. Los problemas identificados con mayor frecuencia en las quejas con mala práctica fueron: perforación de duramadre, seguida por la encefalopatía anoxoisquémica, el tercer lugar para daño cerebral irreversible y lesión de raíces nerviosas. Se identificaron 5 defunciones relacionadas con la anestesia. Los resultados obtenidos en el presente trabajo en cuanto a los problemas en la práctica de la anestesiología son muy semejantes a los reportados en la literatura y una proporción de casos pueden ser prevenibles a través de una mejor capacitación y supervisión de los procedimientos anestésicos que se realizan