RESUMEN
During smooth pursuit, the image of the target is stabilized on the fovea, implying that speed judgments made during pursuit must rely on an extraretinal signal providing precise eye speed information. To characterize the introduction of such extraretinal signal into the human visual system, we performed a factorial, functional magnetic resonance imaging experiment, in which we manipulated the factor eye movement, with "fixation" and "pursuit" as levels, and the factor task, with "speed" and "form" judgments as levels. We hypothesized that the extraretinal speed signal is reflected as an interaction between speed judgments and pursuit. Random effects analysis yielded an interaction only in dorsal early visual cortex. Retinotopic mapping localized this interaction on the horizontal meridian (HM) between dorsal areas visual 2 and 3 (V2/V3) at 1-2 degrees azimuth. This corresponded to the position the pursuit target would have reached, if moving retinotopically, at the time of the subject's speed judgment. Because the 2 V2/V3 HMs are redundant, both may be involved in speed judgments, the ventral one involving judgments based on retinal motion and the dorsal one judgments requiring an internal signal. These results indicate that an extraretinal speed signal is injected into early visual cortex during pursuit.
Asunto(s)
Potenciales de Acción/fisiología , Percepción de Movimiento/fisiología , Seguimiento Ocular Uniforme/fisiología , Retina/fisiología , Corteza Visual/fisiología , Vías Visuales/fisiología , Adulto , Mapeo Encefálico , Aprendizaje Discriminativo/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Estimulación Luminosa , Tiempo de Reacción/fisiología , Retina/anatomía & histología , Corteza Visual/anatomía & histología , Vías Visuales/anatomía & histología , Adulto JovenRESUMEN
A recombinant vaccinia has been designed to express amino acids 366-379 of influenza nucleoprotein, previously shown to be the minimal epitope recognized by a class I-restricted cytotoxic T cell clone. Target cells infected with the recombinant vaccinia virus expressing this peptide are recognized by CTL as efficiently as target cells expressing the complete nucleoprotein. The results imply the existence of a peptide transport system that constitutively passes the products of degraded proteins from the cytoplasm into a membrane-bound compartment of the cell.
Asunto(s)
Epítopos/análisis , Antígenos de Histocompatibilidad Clase I/inmunología , Virus de la Influenza A/inmunología , Nucleoproteínas/inmunología , Fragmentos de Péptidos/inmunología , Proteínas de Unión al ARN , Linfocitos T Citotóxicos/inmunología , Proteínas del Núcleo Viral , Proteínas Virales/inmunología , Animales , Citoplasma/metabolismo , Ratones , Ratones Endogámicos CBA , Proteínas de la Nucleocápside , Nucleoproteínas/biosíntesis , Virus Vaccinia/metabolismo , Proteínas Virales/biosíntesisRESUMEN
The conserved epitopes of influenza nucleoprotein (NP) recognized by class I MHC-restricted CTL from CBA (H-2k) and C57BL/10 (H-2b) mice have been defined in vitro with synthetic peptides 50-63 and 365-379, respectively. Two Db-restricted clones were described that recognize different epitopes on peptide 365-379. Finally, the recognition of complete NP was shown to be approximately 200-fold less efficient than peptide in the cytotoxicity assay. These phenomena are closely related to results with class II-restricted T cells and they strengthen the hypothesis that influenza proteins are degraded in the infected cell before recognition by class I-restricted CTL.
Asunto(s)
Epítopos/análisis , Antígenos de Histocompatibilidad/inmunología , Virus de la Influenza A/inmunología , Nucleoproteínas/inmunología , Linfocitos T Citotóxicos/inmunología , Proteínas Virales/inmunología , Secuencia de Aminoácidos , Animales , Pruebas Inmunológicas de Citotoxicidad , Femenino , Ratones , Ratones Endogámicos C57BLRESUMEN
We have constructed two chimeric influenza hemagglutinin (HA) genes in which the HA1 and HA2 subunits of the HA molecule have been interchanged between influenza A/PR/8/34 (H1 subtype) and A/NT/60/68 (H3 subtype). These genes were used to construct recombinant vaccinia viruses that expressed intact chimeric HA. These recombinant viruses were used to test whether murine CTL recognize antigenic determinants in either the HA1, HA2, or both subunits. We found that both subunits of the HA molecule contain determinants for CTL. This implies that CTL have, at least in part, separate antigenic determinants from B lymphocytes, which recognize mainly epitopes within the HA1 subunit.
Asunto(s)
Antígenos Virales/inmunología , Epítopos/inmunología , Hemaglutininas/inmunología , Virus de la Influenza A/inmunología , Linfocitos T Citotóxicos/inmunología , Animales , ADN/genética , ADN Recombinante , Femenino , Antígenos H-2/inmunología , Hemaglutininas/genética , Virus de la Influenza A/genética , Ratones , Ratones Endogámicos CBA , Virus Vaccinia/genéticaRESUMEN
Vaccinia infection interferes with the presentation of influenza Haemagglutinin (HA) and Nucleoprotein (NP) to class I-restricted CTL. The inhibitory effect is selective for certain epitopes, and is more profound during the late phase of infection. For influenza A/NT/60/68 NP, the block is present during both early and late phases of infection, and is selective for the COOH-terminal epitope defined by peptide 366-379, having no detectable effect on the presentation of the NH2-terminal epitope 50-63. The presentation of HA is inhibited only during the late phase of vaccinia infection. For both proteins, presentation is partially (NP) or completely (HA) restored by expression of rapidly degraded protein fragments in the vaccinia infected target cell. For HA, deletion of the NH2-terminal signal sequence completely overcomes the block. For NP, either a large NH2-terminal deletion or the construction of a rapidly degraded ubiquitin-NP fusion protein partially restores presentation. These results illustrate the relationship between degradation of viral proteins in the cytoplasm of an infected cell and recognition of epitopes at the cell surface by class I-restricted T cells.
Asunto(s)
Hemaglutininas Virales/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Orthomyxoviridae/inmunología , Linfocitos T Citotóxicos/inmunología , Virus Vaccinia/inmunología , Animales , Células Cultivadas , Epítopos/inmunología , Femenino , Vectores Genéticos , Hemaglutininas Virales/genética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Nucleoproteínas/inmunología , Fragmentos de Péptidos/inmunología , Pruebas de Precipitina , Regiones Promotoras Genéticas , Señales de Clasificación de Proteína/genética , Señales de Clasificación de Proteína/inmunología , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Virus Vaccinia/genéticaRESUMEN
Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency is an inborn mitochondrial fatty-acid beta-oxidation (FAO) defect associated with a broad mutational spectrum, with phenotypes ranging from fatal cardiopathy in infancy to adolescent-onset myopathy, and for which there is no established treatment. Recent data suggest that bezafibrate could improve the FAO capacities in beta-oxidation-deficient cells, by enhancing the residual level of mutant enzyme activity via gene-expression stimulation. Since VLCAD-deficient patients frequently harbor missense mutations with unpredictable effects on enzyme activity, we investigated the response to bezafibrate as a function of genotype in 33 VLCAD-deficient fibroblasts representing 45 different mutations. Treatment with bezafibrate (400 microM for 48 h) resulted in a marked increase in FAO capacities, often leading to restoration of normal values, for 21 genotypes that mainly corresponded to patients with the myopathic phenotype. In contrast, bezafibrate induced no changes in FAO for 11 genotypes corresponding to severe neonatal or infantile phenotypes. This pattern of response was not due to differential inductions of VLCAD messenger RNA, as shown by quantitative real-time polymerase chain reaction, but reflected variable increases in measured VLCAD residual enzyme activity in response to bezafibrate. Genotype cross-analysis allowed the identification of alleles carrying missense mutations, which could account for these different pharmacological profiles and, on this basis, led to the characterization of 9 mild and 11 severe missense mutations. Altogether, the responses to bezafibrate reflected the severity of the metabolic blockage in various genotypes, which appeared to be correlated with the phenotype, thus providing a new approach for analysis of genetic heterogeneity. Finally, this study emphasizes the potential of bezafibrate, a widely prescribed hypolipidemic drug, for the correction of VLCAD deficiency and exemplifies the integration of molecular information in a therapeutic strategy.
Asunto(s)
Acil-CoA Deshidrogenasa de Cadena Larga/deficiencia , Acil-CoA Deshidrogenasa de Cadena Larga/genética , Bezafibrato/uso terapéutico , Hipolipemiantes/uso terapéutico , Errores Innatos del Metabolismo Lipídico/genética , Acil-CoA Deshidrogenasa de Cadena Larga/química , Acil-CoA Deshidrogenasa de Cadena Larga/metabolismo , Animales , Células Cultivadas , Ácidos Grasos/metabolismo , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Fibroblastos/patología , Terapia Genética/métodos , Genotipo , Humanos , Errores Innatos del Metabolismo Lipídico/enzimología , Modelos Moleculares , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , Ratas , Piel/citología , Piel/enzimología , Piel/patologíaRESUMEN
The infrared absorption properties of lunar rock throughout the range 2 to 2000 micrometers were investigated and, in addition, direct measurements of specific heat and thermal conductivity of rock samples were made. The results suggest that pure radiation is an important, if not dominant, process in heat flow in the lunar surface layer. A new method for determining the mean conductivity of this layer gives somewhat lower values than earlier earth-based measurements. There is also evidence to suggest that, at depths of about 10 meters, the rock is still of a porous and fragmental nature.
RESUMEN
Enzyme defects in the mitochondrial fatty acid oxidation (FAO) are a large family of inherited metabolic disease well characterized clinically and genetically, but for which pharmacological strategies remain limited. It is now well established that regulation of genes involved in mitochondrial FAO is under control of the PPAR (peroxisome proliferator activated receptor) signalling pathway, and this led us to test a possible pharmacological correction of FAO disorders by fibrates and other PPAR activators. This review presents the basic data supporting our initial hypothesis, summarizes the results obtained in cells from patients with CPT II (carnitine palmitoyltransferase II) or VLCAD (very long-chain acyl-CoA dehydrogenase) deficiency, and discusses the perspectives and limits of this approach for therapy of these disorders.
Asunto(s)
Ácidos Grasos/metabolismo , Errores Innatos del Metabolismo Lipídico/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Enfermedades Mitocondriales/tratamiento farmacológico , PPAR gamma/agonistas , Acil-CoA Deshidrogenasa de Cadena Larga/deficiencia , Acil-CoA Deshidrogenasa de Cadena Larga/metabolismo , Animales , Carnitina O-Palmitoiltransferasa/deficiencia , Síndromes Congénitos de Insuficiencia de la Médula Ósea , Humanos , Errores Innatos del Metabolismo Lipídico/genética , Errores Innatos del Metabolismo Lipídico/metabolismo , Mitocondrias/metabolismo , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/metabolismo , Enfermedades Musculares/tratamiento farmacológico , Enfermedades Musculares/metabolismo , Oxidación-Reducción , PPAR gamma/metabolismoRESUMEN
The peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor implicated in the control of cellular lipid utilization. To test the hypothesis that PPARalpha is activated as a component of the cellular lipid homeostatic response, the expression of PPARalpha target genes was characterized in response to a perturbation in cellular lipid oxidative flux caused by pharmacologic inhibition of mitochondrial fatty acid import. Inhibition of fatty acid oxidative flux caused a feedback induction of PPARalpha target genes encoding fatty acid oxidation enzymes in liver and heart. In mice lacking PPARalpha (PPARalpha-/-), inhibition of cellular fatty acid flux caused massive hepatic and cardiac lipid accumulation, hypoglycemia, and death in 100% of male, but only 25% of female PPARalpha-/- mice. The metabolic phenotype of male PPARalpha-/- mice was rescued by a 2-wk pretreatment with beta-estradiol. These results demonstrate a pivotal role for PPARalpha in lipid and glucose homeostasis in vivo and implicate estrogen signaling pathways in the regulation of cardiac and hepatic lipid metabolism.
Asunto(s)
Errores Innatos del Metabolismo de los Carbohidratos/fisiopatología , Retroalimentación , Glucosa/metabolismo , Errores Innatos del Metabolismo Lipídico/fisiopatología , Receptores Citoplasmáticos y Nucleares/deficiencia , Factores Sexuales , Factores de Transcripción/deficiencia , Animales , Carnitina O-Palmitoiltransferasa/antagonistas & inhibidores , Compuestos Epoxi/farmacología , Estradiol/farmacología , Ácidos Grasos/metabolismo , Femenino , Glucógeno/metabolismo , Hipoglucemia , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Miocardio/metabolismo , Oxidación-ReducciónRESUMEN
Schepaschenko et al question our findings, claiming that we did not refer to all existing maps and that we did not account for all sources of uncertainty. In our response, we detail our selection criteria for reference maps, which clarify why the work of Schepaschenko et al was not used, and we explain why our uncertainty assessment is complete and how it was misunderstood by Schepaschenko et al.
Asunto(s)
Bosques , Humanos , IncertidumbreRESUMEN
Griffith et al do not question the quality of our analysis, but they question our results with respect to the definition of forest we employed. In our response, we explain why the differences we report result from a difference of technique and not of definition, and how anyone can adapt-as we did-our data set to any forest definition and tree cover threshold of interest.
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Bosques , ÁrbolesRESUMEN
De la Cruz et al question the reliability of our results, claiming that we do not refer to the most appropriate spatial extent of drylands. In our response, we explain why we chose an existing and internationally recognized delineation of drylands among several options, and why our findings are due to a difference of remote sensing technique and not to the definition of drylands we have selected.
Asunto(s)
Bosques , Humanos , Reproducibilidad de los ResultadosRESUMEN
Exposure to fibrates leads to normalization of fatty acid oxidation (FAO) in fibroblasts from patients with myopathic forms of CPT2 deficiency or VLCAD deficiency. Correction of FAO is related to a drug-induced increase of residual enzyme activity, and this could provide a new treatment strategy for these disorders.
Asunto(s)
Ácido Clofíbrico/farmacología , Fibroblastos/efectos de los fármacos , Hipolipemiantes/farmacología , Errores Innatos del Metabolismo Lipídico/tratamiento farmacológico , PPAR gamma/agonistas , Acil-CoA Deshidrogenasa de Cadena Larga/biosíntesis , Acil-CoA Deshidrogenasa de Cadena Larga/deficiencia , Acil-CoA Deshidrogenasa de Cadena Larga/genética , Bezafibrato/farmacología , Carnitina O-Palmitoiltransferasa/biosíntesis , Carnitina O-Palmitoiltransferasa/deficiencia , Carnitina O-Palmitoiltransferasa/genética , Células Cultivadas , Ácido Clofíbrico/uso terapéutico , Inducción Enzimática/efectos de los fármacos , Ácidos Grasos/metabolismo , Fibroblastos/enzimología , Humanos , Hipolipemiantes/uso terapéutico , Errores Innatos del Metabolismo Lipídico/genética , Errores Innatos del Metabolismo Lipídico/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Oxidación-Reducción/efectos de los fármacos , PPAR gamma/metabolismo , ARN Mensajero/biosíntesisRESUMEN
High-frequency deep brain stimulation of the subthalamic nucleus can be used to treat severe obsessive-compulsive disorders that are refractory to conventional treatments. The mechanisms of action of this approach possibly rely on the modulation of associative-limbic subcortical-cortical loops, but remain to be fully elucidated. Here in 12 patients, we report the effects of high-frequency stimulation of the subthalamic nucleus on behavior, and on electroencephalographic responses and inferred effective connectivity during motor inhibition processes involved in the stop signal task. First, we found that patients were faster to respond and had slower motor inhibition processes when stimulated. Second, the subthalamic stimulation modulated the amplitude and delayed inhibition-related electroencephalographic responses. The power of reconstructed cortical current densities decreased in the stimulation condition in a parietal-frontal network including cortical regions of the inhibition network such as the superior parts of the inferior frontal gyri and the dorsolateral prefrontal cortex. Finally, dynamic causal modeling revealed that the subthalamic stimulation was more likely to modulate efferent connections from the basal ganglia, modeled as a hidden source, to the cortex. The connection from the basal ganglia to the right inferior frontal gyrus was significantly decreased by subthalamic stimulation. Beyond motor inhibition, our study thus strongly suggests that the mechanisms of action of high-frequency subthalamic stimulation are not restricted to the subthalamic nucleus, but also involve the modulation of distributed subcortical-cortical networks.
Asunto(s)
Encéfalo/fisiopatología , Estimulación Encefálica Profunda , Inhibición Neural/fisiología , Trastorno Obsesivo Compulsivo/fisiopatología , Trastorno Obsesivo Compulsivo/terapia , Desempeño Psicomotor/fisiología , Núcleo Subtalámico/fisiopatología , Adulto , Mapeo Encefálico , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiopatología , Vías Nerviosas/fisiopatología , Tiempo de Reacción/fisiologíaRESUMEN
Pyruvate carboxylase (PC) is a biotin-containing mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate, thereby being involved in gluconeogenesis and in energy production through replenishment of the tricarboxylic acid (TCA) cycle with oxaloacetate. PC deficiency is a very rare metabolic disorder. We report on a new patient affected by the moderate form (the American type A). Diagnosis was nearly fortuitous, resulting from the revision of an initial diagnosis of mitochondrial complex IV (C IV) defect. The patient presented with severe lactic acidosis and pronounced ketonuria, associated with lethargy at age 23 months. Intellectual disability was noted at this time. Amino acids in plasma and organic acids in urine did not show patterns of interest for the diagnostic work-up. In skin fibroblasts PC showed no detectable activity whereas biotinidase activity was normal. We had previously reported another patient with the severe form of PC deficiency and we show that she also had secondary C IV deficiency in fibroblasts. Different anaplerotic treatments in vivo and in vitro were tested using fibroblasts of both patients with 2 different types of PC deficiency, type A (patient 1) and type B (patient 2). Neither clinical nor biological effects in vivo and in vitro were observed using citrate, aspartate, oxoglutarate and bezafibrate. In conclusion, this case report suggests that the moderate form of PC deficiency may be underdiagnosed and illustrates the challenges raised by energetic disorders in terms of diagnostic work-up and therapeutical strategy even in a moderate form.
RESUMEN
Large tropical trees and a few dominant species were recently identified as the main structuring elements of tropical forests. However, such result did not translate yet into quantitative approaches which are essential to understand, predict and monitor forest functions and composition over large, often poorly accessible territories. Here we show that the above-ground biomass (AGB) of the whole forest can be predicted from a few large trees and that the relationship is proved strikingly stable in 175 1-ha plots investigated across 8 sites spanning Central Africa. We designed a generic model predicting AGB with an error of 14% when based on only 5% of the stems, which points to universality in forest structural properties. For the first time in Africa, we identified some dominant species that disproportionally contribute to forest AGB with 1.5% of recorded species accounting for over 50% of the stock of AGB. Consequently, focusing on large trees and dominant species provides precise information on the whole forest stand. This offers new perspectives for understanding the functioning of tropical forests and opens new doors for the development of innovative monitoring strategies.
Asunto(s)
Bosques , Modelos Biológicos , África , BiomasaRESUMEN
The expression of the biogenic amine degrading enzyme monoamine oxidases-A and -B depends on several factors including regional distribution, development and hormonal environment. In the present study, we investigated the expression of monoamine oxidases in developing kidney and their regulation by dexamethasone treatment. Immunoblots and enzyme assays, performed using [14C]5-hydroxytriptamine and [14C]beta-phenylethylamine as substrates for monoamine oxidases-A and -B, respectively, showed that monoamine oxidase-A is the isoenzyme largely predominant in 9-day-old rats renal cortex. Experiments performed in 5-week-old rats showed an increase in monoamine oxidase-B activity and a decrease in monoamine oxidase-A activity and substrate affinity. The changes of monoamine oxidase-A activity and affinity were mimicked by dexamethasone treatment (0.60 mg/kg body weight injected subcutaneously three times at intervals of 24 h) of 9-day-old rats. In contrast, dexamethasone administration induced a modification of monoamine oxidase-B activity opposite to that found between 9-day- and 5-week-old rats. Dexamethasone treatment did not modify immunoreactivity and mRNA corresponding to monoamine oxidases-A and -B indicating that changes of enzyme activities were unrelated to regulation of protein synthesis and mRNA turnover. These results show that monoamine oxidases-A and -B are differently expressed in developing renal cortex and are regulated by dexamethasone treatment.
Asunto(s)
Corteza Renal/enzimología , Monoaminooxidasa/metabolismo , Animales , Antiinflamatorios/farmacología , Dexametasona/farmacología , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Immunoblotting , Corteza Renal/efectos de los fármacos , Corteza Renal/crecimiento & desarrollo , Masculino , Monoaminooxidasa/efectos de los fármacos , Monoaminooxidasa/genética , Fenetilaminas/metabolismo , Embarazo , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serotonina/metabolismo , Especificidad por SustratoRESUMEN
For several years, quality of life is used as a measure of health status. As university constitues a specific setting for young adults, the Health Service of the french-speaking Free University of Brussels initiated a survey in order to study health behaviours of students from the first grade. During the academic year 1998-99, 3,185 students were surveyed in the first degree, using an anonymous self-completed questionnaire with the following topics: health perception, weight, social support, emotional well-being, tobacco, alcohol, medicines, cannabis and ecstasy use as well as access to general practitioner. Body Mass Index was computed and emotional well-being was approached using CES-D scale. Results are presented by gender and faculty. Mutivariate analysis was also realised using logistic regression. In general, results confirm the data resulting from other studies in general population as well as at school. Nevertheless, results show that health is a problem for a minority of students and is a "whole" that has to be approached globally. Moreover, data give a basis to define priorities and strategies to improve students' physical and mental well-being at university. Results are also useful to better target these actions to those at needs.
Asunto(s)
Conductas Relacionadas con la Salud , Estado de Salud , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Universidades , Adulto , Actitud Frente a la Salud , Bélgica/epidemiología , Índice de Masa Corporal , Femenino , Prioridades en Salud , Accesibilidad a los Servicios de Salud/normas , Encuestas Epidemiológicas , Humanos , Modelos Logísticos , Masculino , Salud Mental , Análisis Multivariante , Evaluación de Necesidades , Características de la Residencia/estadística & datos numéricos , Apoyo Social , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/psicología , Encuestas y Cuestionarios , Salud UrbanaRESUMEN
The subthalamic nucleus (STN) has been shown to be implicated in the control of voluntary action, especially during tasks involving conflicting choice alternatives or rapid response suppression. However, the precise role of the STN during nonmotor functions remains controversial. First, we tested whether functionally distinct neuronal populations support different executive control functions (such as inhibitory control or error monitoring) even within a single subterritory of the STN. We used microelectrode recordings during deep brain stimulation surgery to study extracellular activity of the putative associative-limbic part of the STN while patients with severe obsessive-compulsive disorder performed a stop-signal task. Second, 2-4 days after the surgery, local field potential recordings of STN were used to test the hypothesis that STN oscillations may also reflect executive control signals. Extracellular recordings revealed three functionally distinct neuronal populations: the first one fired selectively before and during motor responses, the second one selectively increased their firing rate during successful inhibitory control, and the last one fired selectively during error monitoring. Furthermore, we found that beta band activity (15-35 Hz) rapidly increased during correct and incorrect behavioral stopping. Taken together, our results provide critical electrophysiological support for the hypothesized role of the STN in the integration of motor and cognitive-executive control functions.
Asunto(s)
Atención/fisiología , Función Ejecutiva/fisiología , Inhibición Neural/fisiología , Neuronas/fisiología , Núcleo Subtalámico/fisiología , Adulto , Ritmo beta/fisiología , Terapia por Estimulación Eléctrica , Femenino , Humanos , Masculino , Microelectrodos , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/fisiopatología , Trastorno Obsesivo Compulsivo/psicología , Desempeño Psicomotor/fisiologíaRESUMEN
Carnitine palmitoyltransferase 2 (CPT2) deficiency is a rare mitochondrial fatty acid oxidation (FAO) disorder characterized by myalgia, exercise intolerance, and rhabdomyolysis. We evaluate the efficacy of bezafibrate (BZ), a hypolipidemic drug, as a treatment for this form of CPT2 deficiency. A pilot trial was conducted with BZ in six patients for 6 months. There was a follow-up period of 3 years. The oxidation rates of the long-chain fatty acid derivative palmitoyl-CoA, measured in the mitochondria of the patients' muscles, were markedly lower than normal before treatment and increased significantly (+39 to +206%; P = 0.028) in all patients after BZ treatment. The evaluation of the therapeutic effects by the patients themselves (using the Short Form Health Survey (SF-36)), as well as by the physicians, indicated an improvement in the condition of the patients; there was an increase in physical activity and a decline in muscular pain. The results suggest that BZ has a therapeutic effect in the muscular form of CPT2 deficiency.