RESUMO
Facioscapulohumeral muscular dystrophy (FSHD) is an inherited disease, and although strongly suggested, a contribution of inflammation to its pathogenesis has never been demonstrated. In FSHD patients, we found by immunohistochemistry inflammatory infiltrates mainly composed by CD8(+) T cells in muscles showing hyperintensity features on T2-weighted short tau inversion recovery magnetic resonance imaging (T2-STIR-MRI) sequences. Therefore, we evaluated the presence of circulating activated immune cells and the production of cytokines in patients with or without muscles showing hyperintensity features on T2-STIR-MRI sequences and from controls. FSHD patients displaying hyperintensity features in one or more muscles showed higher CD8(+)pSTAT1(+), CD8(+)T-bet(+) T cells and CD14(+)pSTAT1(+), CD14(+)T-bet(+) cells percentages and IL12p40, IFNγ and TNFα levels than patients without muscles displaying hyperintense features and controls. Moreover, the percentages of CD8(+)pSTAT1(+), CD8(+)T-bet(+) and CD14(+)pSTAT1(+) cells correlated with the proportion of muscles displaying hyperintensity features at T2-STIR sequences. These data indicate that circulating activated immune cells, mainly CD8(+) T cells, may favour FSHD progression by promoting active phases of muscle inflammation.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Imageamento por Ressonância Magnética , Distrofia Muscular Facioescapuloumeral/imunologia , Distrofia Muscular Facioescapuloumeral/patologia , Adulto , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Células Cultivadas , Citocinas/biossíntese , Feminino , Humanos , Inflamação , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Distrofia Muscular Facioescapuloumeral/complicações , Miosite/diagnóstico , Miosite/etiologia , Miosite/imunologia , Miosite/patologia , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Índice de Gravidade de Doença , Proteínas com Domínio T/metabolismoRESUMO
Mixed connective tissue disease (MCTD) is a rheumatological disease which has to be distinguished from other entities causing inflammatory myopathy. The usual clinical presentation of inflammatory myopathy associated with connective tissue disease is not different from isolated polymyositis or dermatomyositis, i.e., subacute onset of proximal weakness affecting both upper and lower girdle with high serum CK level. Here we report a patient with MCTD/myositis overlap syndrome displaying an uncommon clinical presentation and a distribution of muscle weakness involving facial, neck and arm muscles with sparing of lower limbs. We also describe the scarcity of muscle regeneration signs on the muscle biopsy with complete absence of alkaline phosphatase positivity in the endomysial and permysial connective tissue as a novel finding of this condition.
Assuntos
Doenças do Tecido Conjuntivo/diagnóstico , Músculo Esquelético/fisiopatologia , Miosite/fisiopatologia , Regeneração/fisiologia , Adulto , Antígenos CD4/metabolismo , Feminino , Antígenos de Histocompatibilidade Classe I/metabolismo , HumanosRESUMO
Sporadic inclusion-body myositis (s-IBM) is a chronic progressive inflammatory myopathy leading to severe disability. It has been suggested that statins may benefit s-IBM patients based on their pleiotropic effects on autoimmunity and possible adverse influence of increased cholesterol on muscle pathological changes. We carried out a pilot, open-label trial to evaluate safety and tolerability of oral simvastatin in s-IBM patients. Fourteen patients were treated with 40 mg of simvastatin over 12 months. Primary outcome measures included the assessment tools proposed by International Myositis Outcome Assessment Collaborative Study group and the IBM-Functional Rating Scale. As additional data, we report the results obtained from muscle MRI, biopsy and oropharyngeal scintigraphy. Ten patients completed the trial and the treatment appeared safe and well tolerated. None of the patients showed a significant clinical improvement. Outcome measures used in this study proved to be valuable tools for global assessment of s-IBM patients. At present, we cannot recommend simvastatin as a treatment for s-IBM though our data may warrant a placebo-controlled study.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Miosite de Corpos de Inclusão/tratamento farmacológico , Sinvastatina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoimunidade/imunologia , Esquema de Medicação , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Masculino , Pessoa de Meia-Idade , Miosite de Corpos de Inclusão/imunologia , Projetos Piloto , Sinvastatina/administração & dosagem , Resultado do TratamentoRESUMO
Among genes abnormally expressed in myotonic dystrophy type1 (DM1), the myotubularin-related 1 gene (MTMR1) was related to impaired muscle differentiation. Therefore, we analyzed MTMR1 expression in correlation with CUG-binding protein1 (CUG-BP1) and muscleblind-like1 protein (MBNL1) steady-state levels and with morphological features in muscle tissues from DM1 and myotonic dystrophy type 2 (DM2) patients. Semi-quantitative RT-PCR for MTMR1 was done on muscle biopsies and primary muscle cultures. The presence of impaired muscle fiber maturation was evaluated using immunochemistry for neural cell adhesion molecule (NCAM), Vimentin and neonatal myosin heavy chain. CUG-BP1 and MBNL1 steady-state levels were estimated by Western blot. RNA-fluorescence in situ hybridization combined with immunochemistry for CUG-BP1, MBNL1 and NCAM were performed on serial muscle sections. An aberrant splicing of MTMR1 and a significant amount of NCAM-positive myofibers were detected in DM1 and DM2 muscle biopsies; these alterations correlated with DNA repeat expansion size only in DM1. CUG-BP1 levels were increased only in DM1 muscles, while MBNL1 levels were similar among DM1, DM2 and controls. Normal and NCAM-positive myofibers displayed no differences either in the amount of ribonuclear foci and the intracellular distribution of MBNL1 and CUG-BP1. In conclusion, an aberrant MTMR1 expression and signs of altered myofiber maturation were documented in both DM1 and in DM2 muscle tissues. The more severe dysregulation of MTMR1 expression in DM1 versus DM2, along with increased CUG-BP1 levels only in DM1 tissues, suggests that the mutual antagonism between MBNL1 and CUG-BP1 on alternative splicing is more unbalanced in DM1.
Assuntos
Músculos/metabolismo , Distrofia Miotônica/genética , Distrofia Miotônica/metabolismo , Adulto , Processamento Alternativo , Proteínas CELF1 , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Distrofia Miotônica/patologia , Proteínas Tirosina Fosfatases não Receptoras/genética , Proteínas de Ligação a RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Myasthenia gravis (MG) and paraneoplastic cerebellar degeneration (PCD) are immune-mediated syndromes that can represent paraneoplastic disorders. We report a patient with history of ovarian carcinoma that presented with ptosis, diplopia and gait ataxia. Neurophysiological examination and laboratory tests revealed the presence of MG and PCD. An integrated FDG-PET/contrast-enhanced CT scan showed tumor recurrence. This is to the best of our knowledge the first association of MG and PCD with recurring ovarian carcinoma.
Assuntos
Carcinoma/patologia , Miastenia Gravis/patologia , Neoplasias Ovarianas/patologia , Degeneração Paraneoplásica Cerebelar/patologia , Idoso , Carcinoma/diagnóstico por imagem , Feminino , Humanos , Miastenia Gravis/diagnóstico por imagem , Recidiva Local de Neoplasia , Neoplasias Ovarianas/diagnóstico por imagem , Degeneração Paraneoplásica Cerebelar/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios XRESUMO
Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent form of muscular dystrophy. Heart rate variability (HRV) analysis is a means of evaluating the activity of the autonomic nervous system. The aim of this study was to evaluate HRV in FSHD patients. Fifty-five consecutive FSHD patients were enrolled (31 men, age 26-72 years). Muscular impairment was measured using a clinical severity scale (CSS). Patients were compared with a control group of 55 healthy subjects, matched for age and sex. HRV was analyzed in the time domain and in the frequency domain. Patients showed increased spectral power of the low-frequency band. Spectral power of the high-frequency band was inversely correlated with CSS score. FSHD is associated with a slight increase in sympathetic output and with a decrease in parasympathetic output. These modifications become more evident with the progression of the disease and could increase the risk of arrhythmias and other cardiovascular events.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Frequência Cardíaca/fisiologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular Facioescapuloumeral/fisiopatologia , Adulto , Idoso , Bases de Dados Factuais , Eletrocardiografia , Feminino , Análise de Fourier , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
We describe a patient with a familial form of amyotrophic lateral sclerosis (ALS) in which a heterozygous G > A exchange at position 1087 in the SOD1 gene was detected. This mutation results in an amino acid substitution of aspartate for glycine at position 93 (G93D). The patient had a five-year history of fasciculations in all four limbs, with no clear evidence of muscular atrophy or weakness at last follow-up. However, electrophysiological examination revealed lower and upper motor neuron involvement. His mother and a cousin had died of ALS after prolonged disease. This report shows that G93D may cause a form of ALS with slow progression, long-lasting paucisymptomatic phase and both lower and upper motor neuron involvement.
Assuntos
Esclerose Lateral Amiotrófica , Mutação Puntual , Superóxido Dismutase/genética , Idoso , Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/fisiopatologia , Sequência de Bases , Análise Mutacional de DNA , Eletrofisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Superóxido Dismutase-1RESUMO
Cerebral tumor and multiple sclerosis (MS) relapses can show overlapping clinical and magnetic resonance imaging features. In a previous study we observed in relapsing MS patients increased T-bet, pSTAT1, and pSTAT3 expressions in circulating mononuclear cells. During the data analysis we observed that T-bet, pSTAT1, and pSTAT3 expression was not increased in circulating mononuclear cells from a relapsing-remitting (RR)MS patient with recent onset of new neurological signs due to glioblastoma multiforme. In conclusion, our patient represents an exemplary case which suggests that T-bet, pSTAT1, and pSTAT3 expression in peripheral blood mononuclear cells (PBMCs) might be useful to differentiate MS relapses from other noninflammatory diseases.
Assuntos
Neoplasias Encefálicas/complicações , Glioblastoma/complicações , Esclerose Múltipla/complicações , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Glioblastoma/imunologia , Glioblastoma/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Fator de Transcrição STAT1 , Fator de Transcrição STAT3/metabolismo , Linfócitos T ReguladoresRESUMO
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is considered an auto-immune disorder. We evaluated expression of pSTAT1, T-bet, and pSTAT3 in circulating T-cells, B-cells, and monocytes and spontaneous production of interleukin-17 (IL17), interferon-gamma (IFN gamma), and interleukin-10 (IL10) by peripheral blood mononuclear cells (PBMCs) from 14 active CIDP patients compared with 6 patients with long-lasting remission and 20 controls. Active disease patients showed higher pSTAT1, T-bet, and pSTAT3 in CD4(+) T-cells than controls (p < 0.001, p = 0.0002, p = 0.0097, respectively) and remission patients (p < 0.001, p = 0.0036, p = 0.0008, respectively). pSTAT1, T-bet, and pSTAT3 were also higher in monocytes from active CIDP patients than controls (p = 0.0011, p = 0.0041, p = 0.0413, respectively) and remission patients (p = 0.0073, p = 0.0274, p = 0.0251, respectively). Moreover in CD8(+) T-cells, pSTAT3 expression was higher in active CIDP patients than in remission patients (p = 0.0345) and in controls (p = 0.0023). IL17 and IFN gamma production were significantly higher in active CIDP patients than in controls (p < 0.0395, p = 0.0010, respectively); IFN gamma levels were higher also in remission CIDP patients (p = 0.0073). IL10 levels were higher in active phase patients than in controls (p = 0.0334). Our data suggest that pSTAT1, T-bet, and pSTAT3 can be considered putative markers of disease activity and potential targets for specific therapies.
Assuntos
Monócitos/metabolismo , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/sangue , Fator de Transcrição STAT1/sangue , Fator de Transcrição STAT3/sangue , Proteínas com Domínio T/sangue , Linfócitos T/metabolismo , Adolescente , Adulto , Idoso , Linfócitos B/metabolismo , Biomarcadores/sangue , Criança , Feminino , Humanos , Interferon gama/sangue , Interferon gama/metabolismo , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-17/sangue , Interleucina-17/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Fosforilação , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/metabolismo , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas com Domínio T/metabolismo , Adulto JovemRESUMO
Of all the SOD1 gene mutations described, uniquely the D90A mutation has been identified in recessive, dominant, and apparently sporadic cases. We describe a patient with a sporadic form of amyotrophic lateral sclerosis (ALS) in which a heterozygous A > C exchange at position 272 in the SOD1 gene was detected. This mutation results in an amino acid substitution of alanine for aspartate at position 90 (D90A). The patient had a 12-year history of disease characterized by slow progression. Clinical examination at last follow-up revealed predominant upper motor neuron (p-UMN) involvement, with atrophies only in distal muscle of upper limbs. Electrophysiological examination revealed lower and upper motor neuron involvement. Family history was negative for neurological disease. This report shows that D90A in heterozygous state may cause p-UMN phenotype with very slow progression.
Assuntos
Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/fisiopatologia , Doença dos Neurônios Motores/genética , Doença dos Neurônios Motores/fisiopatologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Análise Mutacional de DNA , Progressão da Doença , Família , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Mutação Puntual , Superóxido Dismutase-1 , Fatores de TempoRESUMO
Not all patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) develop clinically defined MS (CDMS). At first clinical event we observed increased production of IL17, IFNgamma and IL10 by peripheral blood mononuclear cells from patients with CIS that remained high in remission. In CD4+ T cells pSTAT3 expression was higher in patients who subsequently converted to CDMS than in patients who did not and controls. The persistency of high levels of pSTAT3 in circulating CD4+ T cells from CIS patients after the first clinical event may favor the early conversion to CDMS.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Esclerose Múltipla/sangue , Esclerose Múltipla/imunologia , Fator de Transcrição STAT3/metabolismo , Adulto , Estudos de Casos e Controles , Citocinas/metabolismo , Progressão da Doença , Feminino , Humanos , Masculino , Adulto JovemRESUMO
We evaluated the spontaneous IL17, IFNgamma and IL10 production by peripheral blood mononuclear cells from patients affected by clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) both in acute phase and in remission, relapsing remitting MS (RRMS) both in relapse and in remission, not-relapsing secondary progressive MS (SPMS) and controls. We observed higher IL17 levels in CIS patients both in acute phase and in remission than in SPMS patients and controls. On the contrary no difference in IL17 production was observed among RRMS patients and CIS, SPMS patients and controls. IFNgamma levels were significantly higher in CIS patients in acute phase than in CIS and RRMS patients in remission, SPMS patients and controls. Moreover, we observed higher IFNgamma spontaneous production in relapsing RRMS patients than in remitting RRMS and SPMS patients and controls. IL10 levels were significantly higher in remitting CIS and in relapsing RRMS patients than in SPMS patients and controls. There was no difference in IFNgamma, IL10 and IL17 levels between SPMS patients and controls. Our data suggest that IL17 might play a crucial role mainly in the early phase of MS, while IFNgamma seems to be involved both in the early phase and in the following relapses of the disease.
Assuntos
Interferon gama/biossíntese , Interleucina-10/biossíntese , Interleucina-17/biossíntese , Leucócitos Mononucleares/metabolismo , Esclerose Múltipla/sangue , Adulto , Doenças Desmielinizantes/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/sangue , Esclerose Múltipla Recidivante-Remitente/sangueRESUMO
Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent inherited muscle disease. Because in FSHD patients the coexistence of affected and unaffected muscles is common, myoblasts expanded from unaffected FSHD muscles have been proposed as suitable tools for autologous cell transplantation. Mesoangioblasts are a new class of adult stem cells of mesodermal origin, potentially useful for the treatment of primitive myopathies of different etiology. Here, we report the isolation and characterization of mesoangioblasts from FSHD muscle biopsies and describe morphology, proliferation, and differentiation abilities of both mesoangioblasts and myoblasts derived from various affected and unaffected muscles of nine representative FSHD patients. We demonstrate that mesoangioblasts can be efficiently isolated from FSHD muscle biopsies and expanded to an amount of cells necessary to transplant into an adult patient. Proliferating mesoangioblasts from all muscles examined did not differ from controls in terms of morphology, phenotype, proliferation rate, or clonogenicity. However, their differentiation ability into skeletal muscle was variably impaired, and this defect correlated with the overall disease severity and the degree of histopathologic abnormalities of the muscle of origin. A remarkable differentiation defect was observed in mesoangioblasts from all mildly to severely affected FSHD muscles, whereas mesoangioblasts from morphologically normal muscles showed no myogenic differentiation block. Our study could open the way to cell therapy for FSHD patients to limit muscle damage in vivo through the use of autologous mesoangioblasts capable of reaching damaged muscles and engrafting into them, without requiring immune suppression or genetic correction in vitro. Disclosure of potential conflicts of interest is found at the end of this article.
Assuntos
Separação Celular , Células-Tronco Mesenquimais/citologia , Distrofia Muscular Facioescapuloumeral/patologia , Mioblastos Esqueléticos/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular/fisiologia , Proliferação de Células , Separação Celular/métodos , Células Cultivadas , Feminino , Humanos , Masculino , Células-Tronco Mesenquimais/fisiologia , Pessoa de Meia-Idade , Distrofia Muscular Facioescapuloumeral/genética , Mioblastos Esqueléticos/fisiologia , Técnicas de Cultura de Órgãos , Índice de Gravidade de DoençaRESUMO
Hereditary aceruloplasminemia (HA) is a rare inherited disease characterized by anemia, iron overload, diabetes, and neurodegeneration. HA is caused by the homozygous mutation of the ceruloplasmin (CP) gene. We report two siblings with markedly different phenotypes carrying a novel mutation: a homozygous deletion of two nucleotides (1257-1258 TT del) causing the premature stop of the Cp protein translation (Y401X). An early diagnosis of iron overload was made in the female sibling who was subsequently treated with deferoxamine. At the age of 54, her neurologic symptoms were limited to mild akinetic signs and a history of seizures; moreover, her fasting blood glucose level never exceeded 120 mg/dL. The male sibling, who had not received any specific treatment for HA, developed severe diabetes at the age of 32 and at 48 manifested a progressively disabling neurologic disease. Possible physiopathological bases of these intrafamilial phenotypic variations are discussed.
Assuntos
Ceruloplasmina/deficiência , Ceruloplasmina/genética , Diabetes Mellitus/genética , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Erros Inatos do Metabolismo dos Metais/genética , Mutação , Encéfalo/metabolismo , Encéfalo/patologia , Ceruloplasmina/metabolismo , Desferroxamina/uso terapêutico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/etiologia , Progressão da Doença , Família , Feminino , Transtornos Heredodegenerativos do Sistema Nervoso/complicações , Transtornos Heredodegenerativos do Sistema Nervoso/diagnóstico , Humanos , Ferro/metabolismo , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Imageamento por Ressonância Magnética , Masculino , Erros Inatos do Metabolismo dos Metais/complicações , Erros Inatos do Metabolismo dos Metais/diagnóstico , Pessoa de Meia-Idade , Fenótipo , Convulsões/etiologiaRESUMO
In this study we observed higher serum leptin levels in relapsing-remitting multiple sclerosis (RRMS) patients during remission than in controls. The expression of leptin receptor (ObR) was higher in CD8+ T cells and monocytes from RRMS patients in relapse than in patients in remission and in controls. Relapsing patients showed high levels of pSTAT3 and low expression of SOCS3 and leptin administration induced an up-regulation of pSTAT3 only in monocytes from patients in relapse. Our data suggest that ObR may be involved in the development of clinical relapses in RRMS patients and suggest a rationale for potential targeting of the leptin axis during MS.
Assuntos
Regulação da Expressão Gênica/fisiologia , Leptina/sangue , Esclerose Múltipla Recidivante-Remitente/sangue , Receptores para Leptina/metabolismo , Fator de Transcrição STAT3/metabolismo , Adulto , Toxinas Bacterianas/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Estudos de Casos e Controles , Citocinas/metabolismo , Feminino , Citometria de Fluxo/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Proteínas Hemolisinas/metabolismo , Humanos , Leptina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Esclerose Múltipla Recidivante-Remitente/patologia , Radioimunoensaio/métodos , Fatores SexuaisRESUMO
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.
Assuntos
Transtornos de Ansiedade/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipotálamo/metabolismo , Musicoterapia , Fator de Crescimento Neural/metabolismo , Estresse Psicológico/metabolismo , Estimulação Acústica , Animais , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/prevenção & controle , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Transtorno Depressivo/metabolismo , Transtorno Depressivo/fisiopatologia , Transtorno Depressivo/terapia , Regulação para Baixo/fisiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Hipotálamo/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Psicológico/fisiopatologia , Estresse Psicológico/prevenção & controle , Regulação para Cima/fisiologiaRESUMO
Amphetamines (methamphetamine and d-amphetamine) are dopaminergic and noradrenergic agonists and are highly addictive drugs with neurotoxic effect on the brain. In human subjects, it has also been observed that amphetamine causes psychosis resembling positive symptoms of schizophrenia. Neurotrophins are molecules involved in neuronal survival and plasticity and protect neurons against (BDNF) are the most abundant neurotrophins in the central nervous system (CNS) and are important survival factors for cholinergic and dopaminergic neurons. Interestingly, it has been proposed that deficits in the production or utilization of neurotrophins participate in the pathogenesis of schizophrenia. In this study in order to investigate the mechanism of amphetamine-induced neurotoxicity and further elucidate the role of neurotrophins in the pathogenesis of schizophrenia we administered intraperitoneally d-amphetamine for 8 days to rats and measured the levels of neurotrophins NGF and BDNF in selected brain regions by ELISA. Amphetamine reduced NGF levels in the hippocampus, occipital cortex and hypothalamus and of BDNF in the occipital cortex and hypothalamus. Thus the present data indicate that chronic amphetamine can reduce the levels of NGF and BDNF in selected brain regions. This reduction may account for some of the effects of amphetamine in the CNS neurons and provides evidences for the role of neurotrophins in schizophrenia.
Assuntos
Anfetamina/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fator de Crescimento Neural/metabolismo , Análise de Variância , Animais , Peso Corporal/efeitos dos fármacos , Encéfalo/anatomia & histologia , Ensaio de Imunoadsorção Enzimática/métodos , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
OBJECTIVE: To evaluate the subjective sleep quality, the prevalence of daytime sleepiness and the risk of sleep-related upper airways obstruction in patients with genetically proven Facioscapulohumeral muscular dystrophy (FSHD). FSHD is an autosomal dominant myopathy, characterized by an early involvement of facial and scapular muscles with eventual spreading to pelvic and lower limb muscles. PATIENTS AND METHODS: Forty-six patients were enrolled, 27 women and 19 men, mean age 43.6+/-14.1 years. Study protocol included: a Clinical Severity Scale (CSS) for FSHD, Pittsburgh Sleep Quality Index (PSQI), Italian version of the Epworth Sleepiness Scale (ESS) and the search for clinical predictors of sleep-related airways obstruction. RESULTS: Twenty-seven patients presented snoring, 12 reported respiratory pauses during sleep. One half (23/46) had PSQI scores above the normal threshold (=5). Correlations were found between the CSS and: the total PSQI score, the components C1 sleep quality, C5 sleep disturbances, C7 daytime dysfunction. CONCLUSION: Our data support the hypothesis that patients with FSHD have an impaired sleep quality, and that this impairment is directly related to the severity of the disease. A systematic polysomnographic evaluation of these patients will be necessary to confirm the presence of sleep disruption and to clarify its pathogenesis.
Assuntos
Distrofia Muscular Facioescapuloumeral/complicações , Transtornos do Sono-Vigília/etiologia , Sono/fisiologia , Adolescente , Adulto , Idoso , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos , Índice de Gravidade de Doença , Estatística como AssuntoRESUMO
Sialorrhea is frequent and invalidating in patients with amyotrophic lateral sclerosis (ALS) or Parkinson's disease (PD). Botulinum toxin (BTX) emerged as an alternative to traditional treatments. We evaluated efficacy and tolerability of ultrasound-guided BTX-B injections in parotids and submandibular glands in 18 patients with ALS or PD. At 1 week, both objective (cotton rolls weight) and subjective evaluations (dedicated clinical scales) documented sialorrhea reduction (p<0.01). ALS patients reported shorter benefit duration (p<0.001) and higher prevalence of viscous saliva (seven vs one patients), possibly due to different pattern of autonomic involvement. BTX-B seems efficacious in reducing sialorrhea in ALS and PD but the risk-benefit ratio might differ between these two conditions. This might have implications for clinical practice.
Assuntos
Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Sialorreia/tratamento farmacológico , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/complicações , Toxinas Botulínicas Tipo A , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Índice de Gravidade de Doença , Sialorreia/etiologia , Fatores de TempoRESUMO
Numerous experimental and clinical studies have shown that skeletal muscle apoptotis may increase in wasting conditions and suggest that apoptosis might contribute to the loss of lean body mass. Data in cancer patients are still lacking. The present study aimed at verifying whether apoptosis was enhanced in the skeletal muscle of 16 patients with gastric cancer with respect to controls. A biopsy specimen was obtained from the rectus abdominis muscle. The occurrence of apoptosis in muscle biopsies was determined morphologically by the fluorescent transferase-mediated dUTP nick end labeling assay and by immunohistochemistry for caspase-3 and caspase-1. Mean weight loss was 6+/-2% in cancer patients and 0.5+/-0.1% in controls (p<0.0001). Serum albumin levels (g/dL) were 3.7+/-0.3 in cancer patients and 4.1+/-0.2 in controls (p<0.05). The percentage of apoptotic myonuclei was similar in cancer patients and in controls (1.5+/-0.3 versus 1.4+/-0.2, respectively; p=ns), in gastric cancer patients with mild (1.6+/-0.4) or moderate-severe weight loss (1.4+/-0.5) (p=ns), and in the different stages of disease (stages I-II: 1.5+/-0.7; stage III: 1.3+/-0.4; stage IV: 1.6+/-0.3; p=ns). By immunohistochemistry, caspase-1 and caspase-3 positive fibers were absent in controls and in neoplastic patients. Poly-ADP-ribosyl polymerase, a typical caspase-3 substrate whose processing is indicative of caspase-3 activation, was not cleaved in muscle biopsies of cancer patients. These data suggest that skeletal muscle apoptosis is not increased in neoplastic patients with mild-moderate weight loss and argue against the hypotheses that caspase-3 activation might be an essential step of myofibrillar proteolysis in cancer-related muscle wasting.