Déficit de vitamina D en personas mayores de 65 años y grado de mejora tras suplementación

Tesis doctoral inédita, leída en la Universidad Autónoma de Madrid. Facultad de Medicina. Departamento de Medicina Preventiva y Salud Pública y MicrobiologíaEl descubrimiento de la amplia gama de funciones de la VD, además de la esquelética ya conocida, ha sido motivo de numerosos estudios en laúltima década. La repercusión que tiene la deficiencia de VD en el organismo y la necesidad o no de suplementar a la población es un tema abierto a debate en la actualidad. En medio de esta controversia y respondiendo a distintos objetivos, este estudio intenta aportar algo de luz, respecto al alcance del problema en la población anciana, que cada vez es más numerosa en las consultas dado el progresivo envejecimiento de la población española. Objetivos: Conocer la prevalencia de hipovitaminosis D en los mayores de 64 años y analizar las variables asociadas a la deficiencia. Estudiar el grado de adherencia al tratamiento suplementario con calcio y VD. Comprobar la mejora de los niveles de VD y si esto supone mejora de las variables de salud y funcionalidad. Métodos: Como fuente de datos se ha utilizado la “Cohorte Peñagrande”, estudio poblacional para analizar la fragilidad y sus factores pronósticos en mayores de 64 años. Forman parte de la muestra inical del estudio 468 individuos en los que se determinó el valor de VD basal y, según éste, se pautó tratamiento suplementario con calcio y VD. Al cabo de 1 año se valoró de nuevo el valor de vitamina. Se analizaron variables sociodemográficas, de salud y funcionalidad antes y después del tratamiento. La adherencia a los suplementos fue medida por el test de Morisky-Green a los 3 y 12 meses. Resultados: El valor basal medio de VD es de 20,32±11,7 ng/mL, y existe una deficiencia grave de VD del 35,2% (IC95%: 30,8-39,7). La insuficiencia vitamínica aumenta con la edad (un 6% por cada año a partir de los 65 años) y con el nivel socioeconómico bajo (OR 3,29; IC95%: 1,55-6,95). La deficiencia grave de vitamina D aumenta con la edad, un 6% de media anual, es más frecuente en las mujeres (OR 1,80; IC95%: 1,18-2,75) y se asocia a deterioro cognitivo (OR 1,71; IC95%:1,04-2,83). De los 468 individuos, 438 tenían hipovitaminosis y fueron tratados 413. El grado de adherencia al tratamiento fue del 63,9% a los 3 meses y desciende al 42,7% a los 12 meses. El incumplimiento al año se asoció a la presencia de comorbilidad (46,3% frente a 35,2%, p=0,027). De los 438 individuos tratados, se obtuvo valor de VD antes y después del tratamiento en 355. El incremento medio de los niveles de VD es de 15,6±16,2 ng/mL, con una mejora superior al 20% en el 75,2% de los El aumento más manifiesto se obtiene en los individuos con niveles más bajos de VD (<15ng/mL) y sin comorbilidad (RR:10,01; IC95%:4,26-23,77 y RR:2,16; IC95%:1,18-3,94 respectivamente). Los pacientes que mejoran el nivel vitamínico más de un 20% tiene 2 veces más probabilidad de mejorar la funcionalidad medida por el SPPB(OR: 2,06; IC95%:1,13-3,77). Conclusiones: La prevalencia de déficit de VD es alta en la población anciana, y aumenta con la edad y con el deterioro cognitivo. La adherencia es mejor en aquellos con nivel menor de vitamina y con ausencia de comorbilidad. La mejora del nivel de VD es importante tras la suplementación y supone una mejora de la capacidad funcional de los individuos

Utilización de servicios de atención primaria, atención especializada y consumo de medicamentos por la población de 65 años y más en la Comunidad de Madrid

Background: Ageing of the Spanish population results in an increa¬se in health services required. Therefore, determine the frequency of the health services utilization in this age group and analyze their determinants has a great interest.The aim was to analyze the utilization of health services among older people living in two urban neighborhoods of northern Madrid. Method: cross-sectional population-based study. It is studied a cohort of 1327 individuals ≥ 65 years, stratified by age and sex. Nine utilization indicators were defined. For each indicator frequencies and the association of each with the other variables were calculated by multivariate analysis. Results: The distribution of indicators expressed as a percentage of the user population is: GP appoiments/month 64.8% (95%CI 62.3 to 67.4); nur¬sing appoiments/month 44.6% (95% CI 41.2 to 47.2); home medical visits/month 3.1% (95%CI 2.2 to 4.1); home nursing visits/month 3% (95%CI 2.1 to 3.9); hospitalization/year 16.4% (95%CI 14.4 to 18.4); appoiments rheumatologist/orthopedic/year 25.1% (95%CI 22.7 to 27.4); physiothera¬pist appoiments/year 12.9% (95% CI 11.1 to 14.7); podiatrist appoiments/year 30.6% (95%CI 28.1 to 33.1) and polypharmacy (≥5 drugs) 55.7% (95% CI 53 to 58.4). Comorbidity was the best predictor of health care utilization ranging from OR 4.10 (95%CI: 3.07-5,49) to OR 1.39 (95%CI: 0.97-1.99) in polymedicated and visit the physiotherapist respectively. Cardiovascular disease (OR 1.34; 95%CI 1.03-1,76) and diabetes (OR 1.46; 95%CI: 1.05 -2.02) were independently associated with increased use of family doctor. Dependence was the main determinant for home healthcare (OR 3.38; 95%CI: 1.38-8.28) and nurses (OR 9.71; 95%CI: 4.19-22.48) Mood disor¬ders were associated to polypharmacy (OR 2.06; 95%CI: 1,48-2.86) and to visits to family doctor (OR 1.52; 95%CI: 1,13-2.04). Conclusions: The comorbidity is the strongest predictor of health ser¬vices utilization. Cardiovascular diseases and diabetes are independently associated to greater use. Dependence is the main determinant of home care. Mood disorders associated with polypharmacy and increased attendances to the General PractitionerFundamento: El envejecimiento de la población española se traduce en un aumento de las prestaciones sanitarias requeridas por la población mayor, por ello conocer la frecuencia de la utilización de los servicios sanitarios de este grupo de edad y analizar sus factores determinantes es de especial interés. El objetivo fue analizar la utilización de servicios sanitarios de la población mayor residente en dos barrios urbanos del norte de Madrid. Métodos: Estudio transversal de base poblacional. Se estudió una cohorte de 1.327 individuos igual o mayor a 65 años, estratificada por edad y sexo. Se definieron 9 indicadores de utilización durante el mes anterio o durante el último año. Para cada indicador se calcularon las frecuencias y la asociación con el resto de variables mediante análisis multivariante. Resultados: la distribución de los indicadores expresada como proporción de la población usuaria fue: consultas médico/mes 64,8% (IC95%:62,3-67,4); consultas enfermería/mes 44,6% (IC95%:41,2-47,2); domicilios médico/mes 3,1% (IC95%:2,2-4,1); domicilios enfermería/mes 3%(IC95%:2,1-3,9); hospitalización/año 16,4% (IC95%:14,4-18,4); consultas reumatólogo/traumatólogo/año 25,1% (IC95%:22,7-27,4); consultas fisioterapeuta/año 12,9% (IC95%:11,1-14,7); consultas podólogo/año 30,6% (IC95%:28,1-33,1) y polimedicados (≥5 fármacos) 55,7% (IC95%: 53-58,4). La comorbilidad fue la variable que mejor predijo la utilización de servicios sanitarios oscilando entre OR 4.10 (IC95%:3.07-5,49) y OR 1,39 (IC95%: 0.97-1.99) para estar polimedicado y visitar al fisioterapeuta respectivamente. Enfermedades cardiovasculares (OR 1,34; IC95%:1.03-1,76) y diabetes (OR 1,46; IC95%:1,05-2,02) se asociaron de forma independiente a mayor utilización del médico de familia. La dependencia fue el principal determinante de atención domiciliaria para el médico (OR 3,38; IC95%: 1,38-8,28) y para enfermería (OR 9.71; IC 95%: 4.19-22.48). Trastornos del ánimo se asociaron a mayor polimedicación (OR 2.06; IC95%: 1,48-2.86) y visitas al médico de familia (OR 1,52; IC 95%:1,13-2.04). Conclusiones: La comorbilidad fue la variable que mejor predijo la utilización de servicios sanitarios. Las enfermedades cardiovasculares y la diabetes se asocian de forma independiente a mayor utilización de servicios. Los trastornos del ánimo se asocian a mayor polimedicación y más visitas al médico de familiaThis project is partially funded with a grant from the Ministry of Health,Instituto de Salud Carlos III (FIS: PI 09/2143) and RETICEF (Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad, RD 06/0013/1013

Laforin, a dual specificity protein phosphatase involved in Lafora disease, is phosphorylated at Ser25 by AMP-activated protein kinase

Carlos Romá-Mateo et alt.Lafora progressive myoclonus epilepsy [LD (Lafora disease)] is a fatal autosomal recessive neurodegenerative disorder caused by loss-of-function mutations in either the EPM2A gene, encoding the dual-specificity phosphatase laforin, or the EPM2B gene, encoding the E3-ubiquitin ligase malin. Previously, we and others showed that laforin and malin form a functional complex that regulates multiple aspects of glycogen metabolism, and that the interaction between laforin and malin is enhanced by conditions activating AMPK (AMP-activated protein kinase). In the present study, we demonstrate that laforin is a phosphoprotein, as indicated by two-dimensional electrophoresis, and we identify Ser25 as the residue involved in this modification. We also show that Ser25 is phosphorylated both in vitro and in vivo by AMPK. Lastly, we demonstrate that this residue plays a critical role for both the phosphatase activity and the ability of laforin to interact with itself and with previously established binding partners. The results of the present study suggest that phosphorylation of laforin-Ser25 by AMPK provides a mechanism to modulate the interaction between laforin and malin. Regulation of this complex is necessary to maintain normal glycogen metabolism. Importantly, Ser25 is mutated in some LD patients (S25P), and our results begin to elucidate the mechanism of disease in these patientsThis work was supported the Spanish Ministry of Education and Science [grant number SAF2008-01907 (to P.S.)]; the Generalitat Valenciana [grant number Prometeo 2009/051 (to P.S.)]; the National Institutes of Health [grant numbers R00NS061803, P20RR020171, R01NS070899 (to M.S.G.)]; and the University of Kentucky College of Medicine startup funds (to M.S.G.)Peer reviewe

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

Global, regional, and national age-sex-specific mortality and life expectancy, 1950-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. Findings: Globally, 18·7% (95% uncertainty interval 18·4–19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2–59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5–49·6) to 70·5 years (70·1–70·8) for men and from 52·9 years (51·7–54·0) to 75·6 years (75·3–75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5–51·7) for men in the Central African Republic to 87·6 years (86·9–88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3–238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6–42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2–5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. Interpretation: This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

Oxidative stress, a new hallmark in the pathophysiology of Lafora progressive myoclonus epilepsy

12 páginas, 4 figuras, 1 tablaLafora disease (LD; OMIM 254780, ORPHA501) is a devastating neurodegenerative disorder characterized by the presence of glycogen-like intracellular inclusions called Lafora bodies and caused, in most cases, by mutations in either the EPM2A or the EPM2B gene, encoding respectively laforin, a phosphatase with dual specificity that is involved in the dephosphorylation of glycogen, and malin, an E3-ubiquitin ligase involved in the polyubiquitination of proteins related to glycogen metabolism. Thus, it has been reported that laforin and malin form a functional complex that acts as a key regulator of glycogen metabolism and that also plays a crucial role in protein homeostasis (proteostasis). Regarding this last function, it has been shown that cells are more sensitive to ER stress and show defects in proteasome and autophagy activities in the absence of a functional laforin-malin complex. More recently, we have demonstrated that oxidative stress accompanies these proteostasis defects and that various LD models show an increase in reactive oxygen species and oxidative stress products together with a dysregulated antioxidant enzyme expression and activity. In this review we discuss possible connections between the multiple defects in protein homeostasis present in LD and oxidative stressThis work was supported by grants from the Spanish Ministry of Education and Science SAF2011-27442 (to P.S.) and BFU2011-22630 (to E.K.), Fundació La Marato de TV3 (ref. 100130, to P.S. and E.K.), Generalitat Valenciana (Prometeo 2009/051, Prometeo 2012/061, to F.V.P.) and an ACCI2012 action from CIBERER, an initiative of the Instituto de Salud Carlos III (to P.S., E. K. and F.V. P.). C. R-M. is supported by the Saving Lives at Birth consortiumPeer reviewe

Increased oxidative stress and impaired antioxidant response in Lafora disease

15 páginas, 10 figurasLafora disease (LD, OMIM 254780, ORPHA501) is a fatal neurodegenerative disorder characterized by the presence of glycogen-like intracellular inclusions called Lafora bodies and caused, in the vast majority of cases, by mutations in either EPM2A or EPM2B genes, encoding respectively laforin and malin. In the last years, several reports have revealed molecular details of these two proteins and have identified several processes affected in LD, but the pathophysiology of the disease still remains largely unknown. Since autophagy impairment has been reported as a characteristic treat in both Lafora disease cell and animal models, and as there is a link between autophagy and mitochondrial performance, we sought to determine if mitochondrial function could be altered in those models. Using fibroblasts from LD patients, deficient in laforin or malin, we found mitochondrial alterations, oxidative stress and a deficiency in antioxidant enzymes involved in the detoxification of reactive oxygen species (ROS). Similar results were obtained in brain tissue samples from transgenic mice deficient in either the EPM2A or EPM2B genes. Furthermore, in a proteomic analysis of brain tissue obtained from Epm2b-/- mice, we observed an increase in a modified form of peroxiredoxin-6, an antioxidant enzyme involved in other neurological pathologies, thus corroborating an alteration of the redox condition. These data support that oxidative stress produced by an increase in ROS production and an impairment of the antioxidant enzyme response to this stress play an important role in development of LDThis work was supported by grants from the Spanish Ministry of Education and Science (SAF2011-27442, BFU2011-22630), Fundació La Marató de TV3 (ref. 100130), EU Funded FRAILOMIC-HEALTH.2012.2.1.1, TREAT-CMT IRDiRC consortium Research fellowship, Generalitat Valenciana (Prometeo 2009/051, Prometeo 2012/061) and an ACCI2012 action from CIBERERPeer reviewe

Lafora disease fibroblasts exemplify the molecular interdependence between thioredoxin 1 and the proteasome in mammalian cells

13 páginas, 8 figuras (que no aparecen en este documento, se pueden consultar en: http://www.sciencedirect.com/science/article/pii/S0891584913003274#ec0005)Thioredoxin 1 (Trx1) is a key regulator of cellular redox balance and participates in cellular signaling events. Recent evidence from yeast indicates that members of the Trx family interact with the 20S proteasome, indicating redox regulation of proteasome activity. However, there is little information about the interrelationship of Trx proteins with the proteasome system in mammalian cells, especially in the nucleus. Here, we have investigated this relationship under various cellular conditions in mammalian cells. We show that Trx1 levels and its subcellular localization (cytosol, endoplasmic reticulum, and nucleus) depend on proteasome activity during the cell cycle in NIH3T3 fibroblasts and under stress conditions, when proteasomes are inhibited. In addition, we also studied in these cells how the main cellular antioxidant systems are stimulated when proteasome activity is inhibited. Finally, we describe a reduction in Trx1 levels in Lafora disease fibroblasts and demonstrate that the nuclear colocalization of Trx1 with 20S proteasomes in laforin-deficient cells is altered compared with control cells. Our results indicate a close relationship between Trx1 and the 20S nuclear proteasome and give a new perspective to the study of diseases or physiopathological conditions in which defects in the proteasome system are associated with oxidative stress.The authors wish to thank to S. Bañuls for their technical support. F.V. Pallardó, P. Sanz and Erwin Knecht are members of the Rare Disease Micro-cluster of VLC Campus of Excellence. This work was supported by grants SAF2008-01338 from the Ministerio de Ciencia e Innovación and financial support from the CIBERER (Biomedical Network Research Center for Rare Diseases). The CIBERER is an initiative of the Instituto de Salud Carlos III and INGENIO 2010Peer reviewe