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1.
Rev Neurol (Paris) ; 179(1-2): 118-122, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36371264

RESUMO

Neuropathy with anti-myelin-associated glycoprotein (MAG) antibodies commonly demonstrates distal-dominant prolongation of nerve conduction. However, recent electrophysiological studies have shown that distal motor demyelination is not always a distinct feature. We aimed to elucidate whether the longitudinal progression of nerve impairment occurs in a distal-dominant manner. Seven patients with neuropathy with anti-MAG antibodies were enrolled. Sequential nerve conduction studies revealed nerve conduction reduction only at the wrist segment in the median nerve of the patients, but not in the ulnar nerve. Median nerve entrapment at the wrist may play a role in longitudinal disease progression in neuropathy with anti-MAG antibodies.


Assuntos
Síndrome do Túnel Carpal , Doenças do Sistema Nervoso Periférico , Humanos , Doenças do Sistema Nervoso Periférico/complicações , Glicoproteína Associada a Mielina , Condução Nervosa , Nervo Mediano
2.
Eur J Neurol ; 27(1): 100-104, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31309642

RESUMO

BACKGROUND AND PURPOSE: Tapering immunosuppressants is desirable in patients with well-controlled myasthenia gravis (MG). However, the association between tapering of calcineurin inhibitor dosage and reduction-associated exacerbation is not known. The aim of this study was to clarify the frequency of reduction-associated exacerbation when tacrolimus is tapered in stable patients with anti-acetylcholine receptor antibody-positive MG, and to determine the factors that predict exacerbations. METHODS: We retrospectively analyzed 115 patients in whom tacrolimus dosage was tapered. The reduction-associated exacerbation was defined as the appearance or worsening of one or more MG symptoms <3 months after the reduction. RESULTS: Tacrolimus dosage was successfully tapered in 110 patients (96%) without any exacerbation. Five patients (4%) experienced an exacerbation, but symptoms were reversed in all patients when the tacrolimus dose was increased to the previous maintenance level. No patient developed an MG crisis. The age at onset was significantly earlier (30 vs. 56 years, P = 0.025) and the reduction in dosage was significantly larger (2.0 vs. 1.0 mg/day, P = 0.002) in patients with reduction-associated exacerbation than in those without exacerbation. The cut-off values determined in a receiver-operating characteristic curve analysis were 52 years (sensitivity, 57%; specificity, 100%) for the age at onset and 1.5 mg (sensitivity, 80%; specificity, 100%) for the dose reduction. CONCLUSION: Tapering of tacrolimus was possible in most patients with well-controlled anti-acetylcholine receptor antibody-positive MG. Early age at onset and a large reduction from maintenance dosage were associated with exacerbation. Reductions ≤1.5 mg/day from the maintenance dosage should be considered for patients with late-onset disease.


Assuntos
Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/imunologia , Receptores Colinérgicos/imunologia , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Adulto , Idade de Início , Anticorpos/análise , Redução da Medicação , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Tacrolimo/efeitos adversos
3.
Mult Scler J Exp Transl Clin ; 3(3): 2055217317729688, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28932409

RESUMO

BACKGROUND: Although predicting future brain volume loss (BVL) in patients with multiple sclerosis (MS) is important, studies have shown only a few biomarkers that can predict BVL. OBJECTIVES: The aim of this study is to elucidate the association between longitudinal BVL and serum biomarker candidates. METHODS: This single-center, retrospective, observational study intended to cover MS patients during January 2008 to March 2016. Patients who underwent brain MRI two times at intervals of >24 months and had a blood test to measure biomarker candidates at the time or within three months of the MRI scan were included. Evaluation of brain volume was performed by using SIENAX and SIENA in the FMRIB software library. RESULTS: Twenty-three patients with MS were included in this study. We found that serum retinol binding protein (RBP) levels were significantly correlated with percentage brain volume change (PBVC) (p = 0.0079). Furthermore, best subset selection of multiple linear regression models identified baseline normalized brain volume and serum RBP as the best predictors of PBVC. CONCLUSIONS: Our study shows that lower serum retinol levels are associated with greater longitudinal BVL and that serum RBP and can be a predictor of BVL.

4.
J Neurochem ; 73(5): 2084-92, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10537068

RESUMO

Midkine (MK) is a new member of the heparin-binding neurotrophic factor family. MK plays important roles in development and carcinogenesis and has several important biological effects, including promotion of neurite extension and neuronal survival. However, the mechanism by which MK exerts its neurotrophic actions on neurons has not been elucidated to date. We have established an apoptosis induction system by serum deprivation in primary neuronal cultures isolated from mouse cerebral cortices. Neuronal apoptosis induced by serum deprivation was accompanied by the activation of caspase-3. MK, when added into the culture medium, inhibited the induction of apoptosis and activation of caspase-3 in a dose-dependent manner. Extracellular signal-regulated kinase (ERK) and Akt were not activated by serum deprivation, whereas ERK and Akt were rapidly activated by addition of MK. In addition, the trophic actions of MK of suppressing apoptosis and suppressing the activation of caspase-3 were abolished by concomitant treatment with PD98059, a specific inhibitor of mitogen-activated protein kinase kinase, and with wort-mannin or LY294002, specific inhibitors of phosphatidyl-inositol 3-kinase (PI 3-kinase). These PI 3-kinase inhibitors also inhibited the activation of ERK in response to MK, demonstrating a link between ERK and the caspase-3 pathway that is modulated by the PI 3-kinase activation. These results indicate that the ERK cascade plays a central role in MK-mediated neuronal survival via inhibition of caspase-3 activation.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas de Transporte/farmacologia , Caspases/farmacologia , Citocinas , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neurônios/enzimologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas , Androstadienos/farmacologia , Animais , Caspase 3 , Células Cultivadas , Córtex Cerebral , Meios de Cultura Livres de Soro , Embrião de Mamíferos , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Marcação In Situ das Extremidades Cortadas , Camundongos , Midkina , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt , Proteínas Recombinantes/farmacologia , Wortmanina
5.
J Neurosci Res ; 54(5): 604-12, 1998 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-9843151

RESUMO

MS-818 (2-piperadino-6-methyl-5-oxo-5, 6-dihydro (7H) pyrrolo [2,3-d]pyrimidine maleate), a newly synthesized heterocyclic pyrimidine derivative, promotes neurite outgrowth in neuronal cell lines. The survival-promoting effect of MS-818 on cultured neurons isolated from mouse cortices was examined. MS-818 promoted neuronal survival by inhibiting apoptosis in a dose-dependent manner. MS-818 treatment also activated mitogen-activated protein kinase (MAPK) of the extracellular signal regulation kinase 2, as demonstrated by Western blot analysis. The MAPK activation level in the cultures treated with MS-818 was almost equivalent to that in cultures treated with nerve growth factor but was less than that in cultures treated with epidermal growth factor and basic fibroblast growth factor (bFGF). MAPK was activated within 3 min after the addition of MS-818, and its activity level returned to baseline within 120 min. Its activation was protein kinase C independent. We further investigated the effect of concurrent treatment with MS-818 and bFGF on neuronal survival. MS-818 enhanced the neuronal survival-promoting effect of bFGF in shifting the half-maximally effective dose from 2.1 ng/ml to 0.036 ng/ml in the sigmoidal dose effect of bFGF and permitted nearly maximum MAPK activation. The enhancement by MS-818 of the neuronal survival-promoting effect of bFGF was accompanied by sustained activation of MAPK to a degree that far exceeded, in magnitude and duration, the cooperative effect of MS-818 and bFGF. These results indicate that MS-818 promotes neuronal survival and enhances the neurotrophic actions of bFGF through stimulation of synchronous signals that may elevate MAPK levels within neurons.


Assuntos
Fator 2 de Crescimento de Fibroblastos/farmacologia , Proteínas Quinases Ativadas por Mitógeno , Neuritos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Células Cultivadas , Córtex Cerebral/citologia , Depressão Química , Sinergismo Farmacológico , Ativação Enzimática/efeitos dos fármacos , Camundongos , Proteína Quinase 1 Ativada por Mitógeno , Proteína Quinase 3 Ativada por Mitógeno , Estrutura Molecular , Proteínas do Tecido Nervoso/metabolismo , Neuritos/ultraestrutura , Fármacos Neuroprotetores/química , Proteína Quinase C/análise , Pirimidinas/química
7.
Rinsho Shinkeigaku ; 35(9): 1044-7, 1995 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-8565345

RESUMO

Recently the incidence of infectious diseases caused by penicillin-resistant Streptococcus pneumoniae (PRSP) is increasing. Patients with meningitis caused by PRSP have been reported with high mortality especially in the field of pediatrics, and it is crucial to treat with accurate and precise choice of antibiotics. We report the first adult case of bacterial meningitis caused by PRSP in Japan. A 32-year-old male without immunological abnormalities developed acute pneumococcal meningitis. Empiric therapy with ampicillin and cefotaxime was not effective and the S. pneumonia from CSF showed resistance to multiple antibiotics such as penicillin and cefotaxime. He was treated successfully with the combination of panipenem/betamipron, vancomycin, and chloramphenicol. We assume that panipenem/betamipron is recommended to be added to empiric therapy of bacterial meningitis, considering an increasing incidence of PRSP infection.


Assuntos
Meningite Pneumocócica/microbiologia , Resistência às Penicilinas , Streptococcus pneumoniae/efeitos dos fármacos , Adulto , Antibacterianos , Quimioterapia Combinada/uso terapêutico , Humanos , Masculino , Meningite Pneumocócica/tratamento farmacológico
8.
Rinsho Shinkeigaku ; 34(8): 838-41, 1994 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-7994994

RESUMO

We reported a 69-year-old man exhibiting Garcin's syndrome caused by adenoid cystic carcinoma of the right submandibular gland. The patient first experienced abnormal sensations in his right cheek, and the cranial nerves on his right side gradually became affected. He was admitted for hoarseness and dysphagia. Physical examination revealed a right submandibular mass, and neurological examination revealed that the first cranial nerve and the fifth to twelfth cranial nerves on the right side were affected. Laboratory examination showed a rise of both serum and cerebrospinal fluid (CSF) ferritin, suggesting an intracranial invasion of the submandibular tumor. But other tumor markers, CSF protein and cell counts, CSF pathologic study and radiological studies for the central nervous system (CNS) were all negative. A submandibular tumor biopsy revealed adenoid cystic carcinoma. The radiation therapy, including the skull base, provided relief of the patient's symptoms, the tumor was reduced and serum and CSF ferritin level decreased. It is possible that CSF ferritin is a sensitive marker for CNS involvement of malignant tumor because of its permeability of the blood brain barrier and the absence of correlation between serum and CSF.


Assuntos
Biomarcadores Tumorais/líquido cefalorraquidiano , Carcinoma Adenoide Cístico/complicações , Doenças dos Nervos Cranianos/etiologia , Ferritinas/líquido cefalorraquidiano , Paralisia/etiologia , Neoplasias da Glândula Submandibular/complicações , Idoso , Neoplasias Encefálicas/diagnóstico , Carcinoma Adenoide Cístico/diagnóstico , Humanos , Masculino , Neoplasias da Glândula Submandibular/diagnóstico
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