Respiratory chain dysfunction associated with multiple mitochondrial DNA deletions in antiretroviral therapy-related lipodystrophy.

Highly-active antiretroviral therapy (HAART) can induce a characteristic lipodystrophy syndrome characterized by peripheral fat wasting and central adiposity, usually associated with hyperlipidaemia and insulin resistance [1,2]. Indirect data have led some authors to propose that mitochondrial dysfunction could play a role in this syndrome [3,4].To date, as recently outlined by Kakuda et al. [5] in this journal, HIV-infected patients developing lipodystrophy have not been studied for mitochondrial changes or respiratory chain capacity...

Modelling the evolution and spread of HIV immune escape mutants.

During infection with human immunodeficiency virus (HIV), immune pressure from cytotoxic T-lymphocytes (CTLs) selects for viral mutants that confer escape from CTL recognition. These escape variants can be transmitted between individuals where, depending upon their cost to viral fitness and the CTL responses made by the recipient, they may revert. The rates of within-host evolution and their concordant impact upon the rate of spread of escape mutants at the population level are uncertain. Here we present a mathematical model of within-host evolution of escape mutants, transmission of these variants between hosts and subsequent reversion in new hosts. The model is an extension of the well-known SI model of disease transmission and includes three further parameters that describe host immunogenetic heterogeneity and rates of within host viral evolution. We use the model to explain why some escape mutants appear to have stable prevalence whilst others are spreading through the population. Further, we use it to compare diverse datasets on CTL escape, highlighting where different sources agree or disagree on within-host evolutionary rates. The several dozen CTL epitopes we survey from HIV-1 gag, RT and nef reveal a relatively sedate rate of evolution with average rates of escape measured in years and reversion in decades. For many epitopes in HIV, occasional rapid within-host evolution is not reflected in fast evolution at the population level.

Predictors of death among patients who completed tuberculosis treatment: a population-based cohort study.

Background: Mortality among patients who complete tuberculosis (TB) treatment is still high among vulnerable populations. The objective of the study was to identify the probability of death and its predictive factors in a cohort of successfully treated TB patients. Methods: A population-based retrospective longitudinal study was performed in Barcelona, Spain. All patients who successfully completed TB treatment with culture-confirmation and available drug susceptibility testing between 1995 1997 were retrospectively followed-up until December 31, 2005 by the Barcelona TB Control Program. Socio-demographic, clinical, microbiological and treatment variables were examined. Mortality, TB Program and AIDS registries were reviewed. Kaplan-Meier and a Cox regression methods with time-dependent covariates were used for the survival analysis, calculating the hazard ratio (HR) with 95% confidence intervals (CI). Results: Among the 762 included patients, the median age was 36 years, 520 (68.2%) were male, 178 (23.4%) HIV-infected, and 208 (27.3%) were alcohol abusers. Of the 134 (17.6%) injecting drug users (IDU), 123 (91.8%) were HIV-infected. A total of 30 (3.9%) recurrences and 173 deaths (22.7%) occurred (mortality rate: 3.4/100 person-years of follow-up). The predictors of death were: age between 4160 years old (HR: 3.5; CI:2.15.7), age greater than 60 years (HR: 14.6; CI:8.924), alcohol abuse (HR: 1.7; CI:1.22.4) and HIV-infected IDU (HR: 7.9; CI:4.713.3). Conclusions: The mortality rate among TB patients who completed treatment is associated with vulnerable populations such as the elderly, alcohol abusers, and HIV-infected IDU. We therefore need to fight against poverty, and promote and develop interventions and social policies directed towards these populations to improve their survival.

Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues

MicroRNAs (miRNAs) are short non-coding RNA molecules playing regulatory roles by repressing translation or cleaving RNA transcripts. Although the number of verified human miRNA is still expanding, only few have been functionally described. However, emerging evidences suggest the potential involvement of altered regulation of miRNA in pathogenesis of cancers and these genes are thought to function as both tumours suppressor and oncogenes. In our study, we examined by Real-Time PCR the expression of 156 mature miRNA in colorectal cancer. The analysis by several bioinformatics algorithms of colorectal tumours and adjacent non-neoplastic tissues from patients and colorectal cancer cell lines allowed identifying a group of 13 miRNA whose expression is significantly altered in this tumor. The most significantly deregulated miRNA being miR-31, miR-96, miR-133b, miR-135b, miR-145, and miR-183. In addition, the expression level of miR-31 was correlated with the stage of CRC tumor. Our results suggest that miRNA expression profile could have relevance to the biological and clinical behavior of colorectal neoplasia.

Una experiencia didáctica con el collage

El punto de partida que Joan Miró estableció para realizar las dieciocho Pintures segons collage de 1933 nos sirven hoy para hacer una propuesta que permita pensar en algunas de las claves de la pintura contemporánea. Términos como la apropiación, la autoría o la subjetividad del artista se ponen en juego cuando se activa el dispositivo del collage como modelo. Aquí se plantea una actividad de aprendizaje que confronta el trabajo individual con el colectivo y que tiene como objetivo principal la reflexión sobre el lenguaje pictórico.

La jurisdicción competente en materia de responsabilidad patrimonial de la Administración: una polémica que no cesa. Comentario a los Autos de la Sala Especial de Conflictos de Competencia del Tribunal Supremo de 27 de diciembre de 2001 y 21 de octubre de 2002 y propuesta de reforma legislativa

En el presente trabajo se comenta la línea jurisprudencial iniciada por el Auto de la Sala Especial de Conflictos de Competencia del Tribunal Supremo de 27 de diciembre de 2001, por la que se atribuye al orden civil la competencia para enjuiciar las demandas dirigidas conjuntamente contra la Administraciónpública y su aseguradora de responsabilidad extracontractual, reabriendo la polémica que parecía zanjada tras la triple reforma legislativa de 1998 y 1999, que afirmó la competencia exclusiva de la jurisdicción contencioso-administrativa para conocer de los pleitos de responsabilidad patrimonial de la Administración.

Indemnizaciones a las victimas del terrorismo

En este informe de legislación, el autor da razón del contenido básico de la Ley 32/1999, de 8 de octubre, de solidaridad con las víctimas del terrorismo, así como de los reglamentos que la desarrollan, aprobados por los Reales Decretos 1.912/1999 y 1.974/1999, de 17 y 23 de diciembre.

La jurisdicció competent en matèria de responsabilitat patrimonial de l'Administració: una polèmica que no acaba. Comentari a les Interlocutòries de la Sala Especial de Conflictes de Competència del Tribunal Suprem de 27 de desembre de 2001 i 21 de octubre de 2002 i proposta de reforma legislativa

En aquest treball es comenta la línia jurisprudencial iniciada per la Interlocutòria de la Sala Especial de Conflictes de Competència del Tribunal Suprem de 27 de desembre de 2001, per la qual s¿atribueix a l'orde civil la competència per jutjar les demandes dirigides conjuntament contra l'Administració pública i la seva asseguradora de responsabilitat extracontractual, reobrint la polèmica que semblava tancada després de la triple reforma legislativa de 1998 i 1999, que afirmà la competència exclusiva de la jurisdicció contenciosa administrativa per conèixer dels plets de responsabilitat patrimonial de l'Administració.

Indemnitzacions a les víctimes del terrorisme

En aquest informe de legislació, l'autor exposa el contingut bàsic de la Llei 32/1999, de 8 d¿octubre, de solidaritat amb les víctimes del terrorisme, així com els reglaments que la desenvolupen, aprovats pels Reials Decrets 1.912/1999 i 1.974/1999, de 17 i 23 de desembre.

Sin opción. Comentario a la STS, 1ª, 17.2.2006, por la que se niega el derecho de opción de las víctimas de exigir responsabilidad civil a los funcionarios públicos ante los órganos de la jurisdicción ordinaria

Actualmente, tras la reforma del art. 146.1 de la Ley 30/1992, de 26 de noviembre, de régimen jurídico de las Administraciones públicas y del procedimiento administrativo común (LRJPAC) llevada a cabo por la Ley 4/1999, de 13 de enero, nadie duda ya que las víctimas de daños causados por los funcionarios y demás agentes públicos en el ejercicio de sus funciones están obligadas a dirigir su reclamación indemnizatoria a la Administración a la que aquellos pertenezcan, sin poder demandarles ante los órganos de la jurisdicción civil en exigencia de su responsabilidad extracontractual. Según el art. 145 LRJPAC, la víctima deberá reclamar directamente a la Administración ­iniciando la tramitación del procedimiento administrativo específico previsto en los arts. 142 y 143 LRJPAC e interponiendo, eventualmente, recurso contencioso-administrativo contra la resolución desestimatoria que le ponga fin­, y ésta, una vez haya satisfecho la indemnización, ejercerá acción de repetición contra el funcionario o agente responsable cuando el mismo haya ocasionado el daño con dolo o culpa grave. Ya no existe, por tanto, el genérico derecho de opción anteriormente reconocido por el art. 43 de la Ley de régimen jurídico de la administración del Estado de 1957.

Canino mandibular incluido: presentación de un caso atípico de abordaje quirúrgico por vía lingual

Se presenta el caso de un paciente varón que tenía el canino temporal inferior derecho no exfoliado a los 15 años de edad; a la exploración se descubrió que existía el canino permanente totalmente incluído, con la particularidad de que estaba asociado a un quiste folicular y que la posible causa de inclusión era la presencia de un premolar supernumerario también retenido; otra rareza a destacar es que se hizo un abordaje quirúrgico mixto, vestibular para el premolar supernumerario y lingual para el canino permanente siendo esta última eventualidad realmente excepcional. Se discuten los aspectos referentes al diagnóstico y a la estrategia quirúrgica adoptadas en este caso poco habitual.

New strategies in the modulation of fatty acid oxidation as a treatment for obesity

Strategies that enhance fat degradation or reduce caloricfood intake could be considered therapeutic interventions to reduce notonly obesity, but also its associated disorders. The enzyme carnitinepalmitoyltransferase 1 (CPT1) is the critical rate-determining regulatorof fatty acid oxidation (FAO) and might play a key role in increasingenergy expenditure and controlling food intake. Our group has shownthat mice overexpressing CPT1 in liver are protected from weight gain,the development of obesity and insulin resistance. Regarding foodintake control, we observed that the pharmacological inhibition ofCPT1 in rat hypothalamus decreased food intake and body weight.This suggests that modulation of CPT1 activity and the oxidation offatty acids in various tissues can be crucial for the potential treatmentof obesity and associated pathologies.

New strategies in the modulation of fatty acid oxidation as a treatment for obesity

Strategies that enhance fat degradation or reduce caloricfood intake could be considered therapeutic interventions to reduce notonly obesity, but also its associated disorders. The enzyme carnitinepalmitoyltransferase 1 (CPT1) is the critical rate-determining regulatorof fatty acid oxidation (FAO) and might play a key role in increasingenergy expenditure and controlling food intake. Our group has shownthat mice overexpressing CPT1 in liver are protected from weight gain,the development of obesity and insulin resistance. Regarding foodintake control, we observed that the pharmacological inhibition ofCPT1 in rat hypothalamus decreased food intake and body weight.This suggests that modulation of CPT1 activity and the oxidation offatty acids in various tissues can be crucial for the potential treatmentof obesity and associated pathologies.