Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 14 de 14
Filtrar
Más filtros

País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Int J Mol Sci ; 25(2)2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38279256

RESUMEN

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder affecting the peripheral nervous system. Despite the established diagnostic criteria, monitoring disease activity and treatment remains challenging. To address this limitation, we investigated serum neurofilament light chain (sNfL) and serum free light chains (sFLCs) as potential biomarkers. A total of 32 CIDP patients undergoing immunoglobulin therapy and 32 healthy controls enrolled in the present study, and agreed to have their blood plasma sNfL and sFLCs analyzed, while CIDP severity was assessed through the modified Rankin Scale (mRS) and the Overall Neuropathy Limitations Scale (ONLS). In line with the immunoglobulin treatment aimed at limiting neuronal damage administered to the majority of patients, sNfL levels did not exhibit significant differences between the two groups. However, CIDP patients showed significantly elevated sFLC and sFLC ratios, while the marker levels did not correlate with the clinical scores. The study confirms the potential of sFLCs as a sensitive biomarker of inflammatory processes in CIDP. Additionally, the present study results regarding neurofilaments strengthen the role of sNfL in monitoring CIDP treatments, confirming the effectiveness of immunoglobulin therapy. Overall, our results demonstrate how combining these markers can lead to better patient characterization for improved treatment.


Asunto(s)
Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Humanos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Filamentos Intermedios , Cadenas Ligeras de Inmunoglobulina , Biomarcadores
2.
Eur J Neurol ; 31(1): e16070, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37724995

RESUMEN

BACKGROUND AND PURPOSE: Hereditary transthyretin amyloidosis (ATTRv) is a life-threatening disease caused by mutations in the gene encoding transthyretin (TTR). The recent therapeutic advances have underlined the importance of easily accessible, objective biomarkers of both disease onset and progression. Preliminary evidence suggests a potential role in this respect for neurofilament light chain (NfL). In this study, the aim was to determine serum NfL (sNfL) levels in a late-onset ATTRv population and evaluate whether it might represent a reliable biomarker of disease onset (i.e., 'conversion' from the asymptomatic status to symptomatic disease in TTR mutation carriers). METHODS: In all, 111 individuals harbouring a pathogenic TTR variant (61 symptomatic ATTRv patients and 50 presymptomatic carriers) were consecutively enrolled. Fifty healthy volunteers were included as the control group. Ella™ apparatus was used to assess sNfL levels. RESULTS: Serum NfL levels were increased in ATTRv patients compared to both presymptomatic carriers and healthy controls, whilst not differing between carriers and healthy controls. An sNfL cut-off of 37.10 pg/mL could discriminate between asymptomatic and symptomatic individuals with high diagnostic accuracy (area under the curve 0.958; p < 0.001), sensitivity (81.4%) and specificity (100%). CONCLUSIONS: Serum NfL seems to be a promising biomarker of peripheral nerve involvement in ATTRv amyloidosis and might become a reliable, objective measure to detect the transition from the presymptomatic stage to the onset of symptomatic disease. Further longitudinal studies are needed to confirm such a role and determine whether it could equally represent a biomarker of disease progression and response to therapy.


Asunto(s)
Neuropatías Amiloides Familiares , Filamentos Intermedios , Humanos , Neuropatías Amiloides Familiares/diagnóstico , Neuropatías Amiloides Familiares/genética , Neuropatías Amiloides Familiares/patología , Estudios Longitudinales , Biomarcadores
4.
Brain Sci ; 12(12)2022 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-36552168

RESUMEN

Hereditary transthyretin (ATTRv) amyloidosis is a severe, progressive, and heterogeneous multisystemic condition due to mutations in the TTR gene. Although multiple aspects of its molecular pathophysiological mechanisms have been elucidated over the years, it is possible to hypothesize different pathogenetic pathways. Indeed, we extensively investigated the serum levels of several molecules involved in the immune response, in a cohort of ATTRv patients and healthy controls (HCs). Sixteen ATTRv patients and twenty-five HCs were included in the study. IFN-alpha levels were higher in ATTRv patients than in HCs, as well as IFN-gamma levels. By contrast, IL-7 levels were lower in ATTRv patients than in HCs. No significant difference between groups was found regarding IL-1Ra, IL-6, IL-2, IL-4, and IL-33 levels. Correlation analysis did not reveal any significant correlation between IFN-α, IFN-γ, IL-7, and demographic and clinical data. Larger and longitudinal studies using ultrasensitive methods to perform a full cytokine profiling are needed to better elucidate the role of inflammation in ATTRv pathogenesis and to test the reliability of these molecules as possible biomarkers in monitoring patients' progression.

5.
Int J Mol Sci ; 23(24)2022 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-36555770

RESUMEN

Hereditary transthyretin amyloidosis is the most common form of hereditary amyloidosis, with an autosomal dominant inheritance and a variable penetrance. ATTRv amyloidosis can present as a progressive, axonal sensory autonomic and motor neuropathy or as an infiltrative cardiomyopathy. The definition of biomarkers for the early diagnosis of ATTRv is particularly important in the current era of emerging treatments. In this sense, metabolomics could be an instrument able to provide metabolic profiles with their related metabolic pathways, and we would propose them as possible fluid biomarkers. The aim of this study is to identify altered metabolites (free fatty acids and amino acids) in subjects with a confirmed pathogenic TTR variant. Out of the studied total free fatty acids and amino acids, the serum values of palmitic acid are significantly lower in the ATTRv patients compared to the recruited healthy subjects. The metabolic remodeling identified in this neurogenetic disorder could be the manifestation of pathophysiological processes of the disease, such as mitochondrial dysfunction and neuroinflammation, and contribute to explaining some of its clinical manifestations.


Asunto(s)
Neuropatías Amiloides Familiares , Amiloidosis Familiar , Humanos , Proyectos Piloto , Ácidos Grasos no Esterificados , Neuropatías Amiloides Familiares/patología , Prealbúmina/genética
6.
Neurol Genet ; 8(4): e200007, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35812164

RESUMEN

Objectives: Topoisomerase III alpha plays a key role in the dissolution of double Holliday junctions and is required for mitochondrial DNA (mtDNA) replication and maintenance. Sequence variants in the TOP3A gene have been associated with the Bloom syndrome-like disorder and described in an adult patient with progressive external ophthalmoplegia. The purpose of this report is to expand the clinical phenotype of the TOP3A-related diseases and clarify the role of this gene in primary mitochondrial disorders. Methods: A 44-year-old woman was referred to our hospital because of exercise intolerance and creatine kinase increase. Muscle biopsy and a targeted next-generation sequencing (NGS) analysis were performed. Results: A histopathologic assessment documented a mitochondrial myopathy, and a molecular analysis revealed a novel homozygous variant in the TOP3A gene associated with multiple mtDNA deletions. Discussion: This case suggests that TOP3A is one of the several nuclear genes associated with mtDNA maintenance disorder and expands the spectrum of its associated phenotypes, ranging from a clinical condition defined Bloom syndrome-like disorder to canonical mitochondrial syndromes.

7.
Neurol Sci ; 43(4): 2845-2848, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35094171

RESUMEN

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is a treatable multisystem disorder with prevalent peripheral nervous system impairment. Besides neurophysiological measures, there are few markers to monitor disease progression. Neurofilament light chain (NfL) has recently been considered a sensitive biomarker for neuroaxonal damage in this setting. OBJECTIVE: To evaluate NfL levels in a cohort of ATTRv patients and pre-symptomatic carriers and correlate the serum concentrations with other markers of disease severity. METHODS: We analysed NfL serum from 17 ATTRv patients or carriers and 26 controls. An exhaustive clinical and instrumental evaluation was performed in all patients. RESULTS: NfL levels were significantly higher in ATTRv cases when compared with controls. A significant correlation was found between NfL values and NIS scale, Sudoscan values from feet, interventricular septum thickness, and Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) questionnaire. CONCLUSION: We confirm that NfL is a reliable and promising biomarker to evaluate the ATTRv severity and monitor its progression.


Asunto(s)
Neuropatías Amiloides Familiares , Neuropatías Amiloides Familiares/diagnóstico , Biomarcadores , Humanos , Filamentos Intermedios , Proteínas de Neurofilamentos , Calidad de Vida , Índice de Severidad de la Enfermedad
8.
Life (Basel) ; 12(1)2021 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-35054398

RESUMEN

The central nervous system is metabolically very demanding and consequently vulnerable to defects of the mitochondrial respiratory chain. While the clinical manifestations and the corresponding radiological findings of the brain involvement in mitochondrial diseases (e.g., stroke-like episodes, signal changes of the basal ganglia, cerebral and cerebellar atrophy) are well known, at present there are few data on the spinal-cord abnormalities in these pathologies, in particular in adult subjects. In this study, we present a cross-sectional cohort study on the prevalence and characterization of spinal-cord involvement in adult patients with genetically defined mitochondrial diseases.

9.
Genes (Basel) ; 11(12)2020 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-33352713

RESUMEN

Primary mitochondrial myopathies (PMM) are a group of mitochondrial disorders characterized by a predominant skeletal muscle involvement. The aim of this study was to evaluate whether the biochemical profile determined by Fourier-transform infrared (FTIR) spectroscopic technique would allow to distinguish among patients affected by progressive external ophthalmoplegia (PEO), the most common PMM presentation, oculopharyngeal muscular dystrophy (OPMD), and healthy controls. Thirty-four participants were enrolled in the study. FTIR spectroscopy was found to be a sensitive and specific diagnostic marker for PEO. In particular, FTIR spectroscopy was able to distinguish PEO patients from those affected by OPMD, even in the presence of histological findings similar to mitochondrial myopathy. At the same time, FTIR spectroscopy differentiated single mtDNA deletion and mutations in POLG, the most common nuclear gene associated with mitochondrial diseases, with high sensitivity and specificity. In conclusion, our data suggest that FTIR spectroscopy is a valuable biodiagnostic tool for the differential diagnosis of PEO with a high ability to also distinguish between single mtDNA deletion and mutations in POLG gene based on specific metabolic transitions.


Asunto(s)
ADN Mitocondrial/genética , Músculo Deltoides/química , Miopatías Mitocondriales/diagnóstico , Espectroscopía Infrarroja por Transformada de Fourier , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Niño , ADN Polimerasa gamma/genética , ADN Mitocondrial/análisis , Músculo Deltoides/patología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miopatías Mitocondriales/genética , Miopatías Mitocondriales/patología , Distrofia Muscular Oculofaríngea/diagnóstico , Distrofia Muscular Oculofaríngea/patología , Oftalmoplejía Externa Progresiva Crónica/diagnóstico , Oftalmoplejía Externa Progresiva Crónica/patología , Sensibilidad y Especificidad , Adulto Joven
10.
Artículo en Español | LILACS | ID: biblio-1087372

RESUMEN

Objetivo. Determinar sentimientos de depresión en personas mayores, beneficiarios de un Programa de Extensión Solidaria de Salud Familiar. Materiales y métodos. Estudio descriptivo, transversal con enfoque cuantitativo, la población estuvo conformada por 111 personas mayores de 60 años de sectores vulnerables, pertenecientes al Programa de Extensión solidaria "Salud Familiar" de la Universidad de Córdoba en la ciudad de Montería, la información se recolectó en el período comprendido entre 2016- II a 2018-I mediante base de datos alimentada con la Escala Yesavage de la historia clínica familiar. Resultados. El 80% de los sujetos de estudio habita en estrato socioeconómico I, el otro restante en estrato 2; los sentimientos de depresión se evidenciaron en 27.9% de las personas mayores, donde leve correspondió a 21.6% y depresión establecida a 6.3%, teniendo más representatividad el sexo femenino con 18%, el estado civil que exteriorizó mayores porcentajes de depresión fue: casadas 9% y unión libre 7.2%. Conclusiones. La mayoría de los adultos mayores no manifestó sentimientos de depresión. Se encontraron como factores protectores tener amigos, pertenecer a grupos sociales, religiosos, buena funcionalidad familiar e indudablemente pertenecer al Programa de Extensión solidaria "Salud Familiar de la Universidad de Córdoba". Es perceptible el incremento de la depresión en la presencia de factores de riesgo tales como problemas de pareja, maltrato, disfuncionalidad familiar y pocas oportunidades de esparcimiento. Se concluye que las actividades educativas, asistenciales y recreativoterapéuticas, desarrolladas durante 2 años continuos lideradas por estudiantes y docentes de Enfermería pudieron influenciar positivamente para evitar o disminuir sentimientos de depresión en esta población vulnerable


Objective. To Determine feelings of depression in older people, who benefit from a Family Health Solidarity Extension Program. Materials and methods. Descriptive, crosssectional study with a quantitative approach, the population selected was 111 adults over 60 years from vulnerable sectors, belonging to the "Family Health" Solidarity Extension Program in the city of Monteria. The information was collected between 2016- II to 2018-I through a database updated by the Yesavage Scale of family medical history. Results. The study subjects live in socioeconomic strata 1, (80%) and 2 (20%). Feelings of depression were evidenced in 27.9% of older people, where mild depression corresponds to 21.6% and the established one 6.3%. The female sex with 18%, being the most representative population affected. Regarding marital status: Married 9% and free union 7.2% which showed higher percentages of depression. Conclusions. The majority of older people showed no feelings of depression. Protective factors were found such as belonging to social and religious groups, to have friends, good family functionality and undoubtedly to belong to the Solidarity Extension Program "Family Health" from Universidad de Córdoba. Increasing depression rates were observed when risk factors appear such as marital problems, abuse, family dysfunctionality and few recreational opportunities. It is concluded that educational, recreational-therapeutic activities, carried out during 2 continuous years by students and nursing teachers influenced positively to avoid or reduce feelings of depression in this vulnerable population.


Asunto(s)
Anciano , Anciano de 80 o más Años , Anciano , Depresión , Enfermería
11.
J Neurol Sci ; 379: 298-303, 2017 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-28716266

RESUMEN

Multiple sclerosis (MS) is a chronic demyelinating central nervous system (CNS) disease that involve oligodendrocyte loss and failure to remyelinate damaged brain areas causing a progressive neurological disability. Studies in MS mouse model suggest that cannabinoids ameliorate symptoms as spasticity, tremor and pain reducing inflammation via cannabinoid-mediated system. The aim of our study is to investigate the changes in cannabinoid type 1 (CNR1) and 2 (CNR2) receptors mRNA expression levels and promoter methylation in peripheral blood mononuclear cells (PBMCs) of MS secondary progressive (MSS-SP) patients treated with Sativex®. Our cohort included MSS-SP patients, that at the time of Sativex® treatment, are treated (n=7), not treated (n=11) or that had terminated interferon-ß-1b (IFN-ß-1b) therapy (n=12). By Methylation Sensitive High Resolution Melting (MS-HRM), we characterized the methylation profile of CNR1 and CNR2 promoter region, while the relative mRNA transcript levels of these two genes were evaluated in the same samples by Quantitative Real-Time PCR (qRT-PCR) analysis. We did not find different pattern of cytosine-phosphate-guanine (CpG) methylation in the CNR1/CNR2 promoter region of all MSS-SP patients treated with Sativex®. In addition, CNR1 and CNR2 expression did not significantly differ in MSS-SP patients not treated with IFN-ß-1b vs. them that have suspended, while in MSS-SP patients treated with IFN-ß-1b during Sativex® therapy we found a specific decrease of the CNR2 expression levels. These results suggest that the different expression of cannabinoid receptors by Sativex® treatment in leukocytes might be regulated through a molecular mechanism that involve interferon modulation.


Asunto(s)
Cannabidiol/farmacología , Dronabinol/farmacología , Leucocitos Mononucleares/metabolismo , Metilación/efectos de los fármacos , Esclerosis Múltiple Crónica Progresiva/genética , Regiones Promotoras Genéticas/genética , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB2/genética , Combinación de Medicamentos , Femenino , Humanos , Interferon beta-1b/farmacología , Interferon beta-1b/uso terapéutico , Masculino , Persona de Mediana Edad
12.
J Neurosci ; 34(25): 8630-45, 2014 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-24948817

RESUMEN

Correlative evidence suggests that GABAergic signaling plays an important role in the regulation of activity-dependent hippocampal neurogenesis and emotional behavior in adult mice. However, whether these are causally linked at the molecular level remains elusive. Nuclear factor of activated T cell (NFAT) proteins are activity-dependent transcription factors that respond to environmental stimuli in different cell types, including hippocampal newborn neurons. Here, we identify NFATc4 as a key activity-dependent transcriptional regulator of GABA signaling in hippocampal progenitor cells via an unbiased high-throughput genome-wide study. Next, we demonstrate that GABAA receptor (GABAAR) signaling modulates hippocampal neurogenesis through NFATc4 activity, which in turn regulates GABRA2 and GABRA4 subunit expression via binding to specific promoter responsive elements, as assessed by ChIP and luciferase assays. Furthermore, we show that selective pharmacological enhancement of GABAAR activity promotes hippocampal neurogenesis via the calcineurin/NFATc4 axis. Importantly, the NFATc4-dependent increase in hippocampal neurogenesis after GABAAR stimulation is required for the suppression of the anxiety response in mice. Together, these data provide a novel molecular insight into the regulation of the anxiety response in mice, suggesting that the GABAAR/NFATc4 axis is a druggable target for the therapy of emotional disorders.


Asunto(s)
Ansiedad/metabolismo , Ansiedad/prevención & control , Factores de Transcripción NFATC/metabolismo , Neurogénesis/fisiología , Receptores de GABA-A/fisiología , Transducción de Señal/fisiología , Animales , Ansiedad/patología , Hipocampo/citología , Hipocampo/metabolismo , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados
13.
Neurosci Lett ; 429(2-3): 152-5, 2007 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-17980967

RESUMEN

It has been reported that music may have physiological effects on blood pressure, cardiac heartbeat, respiration, and improve mood state in people affected by anxiety, depression and other psychiatric disorders. However, the physiological bases of these phenomena are not clear. Hypothalamus is a brain region involved in the regulation of body homeostasis and in the pathophysiology of anxiety and depression through the modulation of hypothalamic-pituitary-adrenal (HPA) axis. Hypothalamic functions are also influenced by the presence of the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which are proteins involved in the growth, survival and function of neurons in the central nervous system. The aim of this study was to investigate the effect of music exposure in mice on hypothalamic levels of BDNF and NGF. We exposed young adult mice to slow rhythm music (6h per day; mild sound pressure levels, between 50 and 60 dB) for 21 consecutive days. At the end of the treatment mice were sacrificed and BDNF and NGF levels in the hypothalamus were measured by enzyme-linked immunosorbent assay (ELISA). We found that music exposure significantly enhanced BDNF levels in the hypothalamus. Furthermore, we observed that music-exposed mice had decreased NGF hypothalamic levels. Our results demonstrate that exposure to music in mice can influence neurotrophin production in the hypothalamus. Our findings also suggest that physiological effects of music might be in part mediated by modulation of neurotrophins.


Asunto(s)
Trastornos de Ansiedad/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipotálamo/metabolismo , Musicoterapia , Factor de Crecimiento Nervioso/metabolismo , Estrés Psicológico/metabolismo , Estimulación Acústica , Animales , Trastornos de Ansiedad/fisiopatología , Trastornos de Ansiedad/prevención & control , Encéfalo/metabolismo , Encéfalo/fisiopatología , Trastorno Depresivo/metabolismo , Trastorno Depresivo/fisiopatología , Trastorno Depresivo/terapia , Regulación hacia Abajo/fisiología , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Hipotálamo/fisiopatología , Masculino , Ratones , Ratones Endogámicos BALB C , Estrés Psicológico/fisiopatología , Estrés Psicológico/prevención & control , Regulación hacia Arriba/fisiología
14.
Behav Pharmacol ; 18(5-6): 491-6, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17762517

RESUMEN

It has been shown that music might be able to improve mood state in people affected by psychiatric disorders, ameliorate cognitive deficits in people with dementia and increase motor coordination in Parkinson patients. Robust experimental evidence explaining the central effects of music, however, is missing. This study was designed to investigate the effect of music on brain neurotrophin production and behavior in the mouse. We exposed young adult mice to music with a slow rhythm (6 h/day; mild sound pressure levels, between 50 and 60 db) for 21 consecutive days. At the end of the treatment, mice were tested for passive avoidance learning and then killed for analysis of brain-derived neurotrophic factor (BDNF) and nerve growth factor with enzyme-linked immunosorbent assay (ELISA) in selected brain regions. We found that music-exposed mice showed increased BDNF, but not nerve growth factor in the hippocampus. Furthermore, we observed that music exposure significantly enhanced learning performance, as measured by the passive avoidance test. Our results demonstrate that exposure to music can modulate the activity of the hippocampus by influencing BDNF production. Our findings also suggest that music exposure might be of help in several central nervous system pathologies.


Asunto(s)
Conducta Animal/fisiología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismo , Música , Análisis de Varianza , Animales , Reacción de Prevención/fisiología , Peso Corporal , Factor Neurotrófico Derivado del Encéfalo/fisiología , Ensayo de Inmunoadsorción Enzimática , Masculino , Ratones , Ratones Endogámicos BALB C , Factor de Crecimiento Nervioso/metabolismo , Factor de Crecimiento Nervioso/fisiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA