RESUMO
The prevalence of multiple sclerosis is associated with geographic latitude. Low sun exposure or reduced daylight hours are considered possible causes. We examined whether a change in the number of daylight hours affects the course of experimental autoimmune encephalomyelitis (EAE) disease. Housing mice in a 24-h dark or light cycle upregulated internal corticosterone secretion and ameliorated the EAE disease course relative to that in mice housed in a conventional 12/12-h cycle environment. After EAE induction, the rhythmic pattern of corticosterone secretion was disrupted. Upregulation of internal steroid secretion might act as an immunosuppressive and ameliorate EAE.
Assuntos
Ritmo Circadiano/fisiologia , Corticosterona/sangue , Encefalomielite Autoimune Experimental , Fotoperíodo , Animais , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Medula Espinal/patologia , Linfócitos T/imunologiaRESUMO
Objective: We examined the clinical and serologic features of Guillain-Barré syndrome (GBS)-related diseases (GBSRDs), including GBS, Fisher syndrome (FS), and Bickerstaff brainstem encephalitis (BBE), after influenza virus infection (GBSRD-I) to reveal potential underlying autoimmune mechanisms. Methods: We retrospectively investigated the presence of antiglycolipid antibodies against 11 glycolipids and the clinical features of 63 patients with GBSRD-I. Autoantibody profiles and clinical features were compared with those of 82 patients with GBSRDs after Campylobacter jejuni infection (GBSRD-C). Results: The anti-GQ1b seropositivity rate was significantly higher, whereas the GM1 and GD1a seropositivity rates were significantly lower in GBSRD-I compared with GBSRD-C. Anti-GQ1b and anti-GT1a were the most frequently detected antiglycolipid antibodies in GBSRD-I (both 15/63, 24%). Consequently, FS was more frequent in GBSRD-I than GBSRD-C (22% vs 9%, p < 0.05). In addition, as for GBS, cranial nerve deficits, sensory disturbances, and ataxia were more frequent in the cases after influenza infection (GBS-I) than in those after C. jejuni infection (GBS-C) (46% vs 15%, 75% vs 46%, and 29% vs 4%, respectively; all p < 0.01). Nerve conduction studies revealed acute inflammatory demyelinating polyneuropathy (AIDP) in 60% of patients with GBS-I but only 25% of patients with GBS-C (p < 0.01). Conclusions: Anti-GQ1b antibodies are the most frequently detected antibodies in GBSRD-I. Compared with GBS-C, GBS-I is characterized by AIDP predominance and frequent presence of cranial nerve involvement and ataxia.
Assuntos
Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/patologia , Influenza Humana/complicações , Influenza Humana/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ataxia , Autoanticorpos/imunologia , Infecções por Campylobacter/complicações , Infecções por Campylobacter/imunologia , Campylobacter jejuni , Criança , Pré-Escolar , Encefalite/imunologia , Feminino , Gangliosídeos/imunologia , Humanos , Infecções/complicações , Infecções/imunologia , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher , Exame Neurológico , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the relationship between antibody reactivities against glycolipid complexes and clinical features in Miller Fisher syndrome (MFS), Bickerstaff brainstem encephalitis (BBE), and Guillain-Barré syndrome with ophthalmoplegia (GBS-OP). METHODS: Using glycoarray, antibodies against 10 glycolipid antigens (GM1, GM2, GM4, GD1a, GD1b, GQ1b, galactocerebroside, lactosylceramide, GA1, and sulfatide) and 45 glycolipid complexes consisting 2 of the glycolipids were examined in the sera of 63 patients with GBS-OP, 37 patients with MFS, and 27 patients with BBE. RESULTS: Antibodies to antigens containing GQ1b were identified in 73% of patients with GBS-OP (46/63), 86.5% of patients with MFS (32/37), and 74.1% of patients with BBE (20/27), and GD1b-related antibodies were identified in 49.2% of patients with GBS-OP (31/63), 29.7% of patients with MFS (11/37), and 11.1% of patients with BBE (3/27). Comparing clinical features between patients with GBS-OP with and without both antibodies, the proportion of patients requiring artificial ventilation and presenting moderate or severe muscle weakness was higher in the positive group than in the negative group (p = 0.017 and p = 0.046, respectively). CONCLUSIONS: Antibodies binding to antigens containing GD1b and to those containing GQ1b may be involved in the development of limb weakness and respiratory failure in anti-GQ1b antibody-related diseases.
RESUMO
We evaluated the effects of a non-specific potassium channel blocker, 4-aminopyridine (4-AP), on chronic experimental autoimmune encephalomyelitis (chEAE) and relapsing remitting EAE (rrEAE) in mice. 4-AP did not affect chEAE, but ameliorated rrEAE, particularly in the relapsing phase. Disease amelioration was confirmed pathologically, and glial fibrillary acidic protein expression was observed to be downregulated in 4-AP-treated mice. In the recall response, a T-cell proliferative response was not inhibited; however, Th1/Th17 polarization was attenuated. 4-AP is currently accepted as an anti-symptomatic drug only in the chronic phase of multiple sclerosis (MS); however, its use in the active phase of MS should be considered.
Assuntos
4-Aminopiridina/uso terapêutico , Encefalomielite Autoimune Experimental/diagnóstico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Bloqueadores dos Canais de Potássio/uso terapêutico , 4-Aminopiridina/farmacologia , Sequência de Aminoácidos , Animais , Encefalomielite Autoimune Experimental/genética , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Bloqueadores dos Canais de Potássio/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/fisiologiaRESUMO
INTRODUCTION: Neurofascin155 (NF155) is a target antigen for autoantibodies in a subset of chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: We report the cases of 4 patients with anti-NF155 immunoglobulin G4 (IgG4) antibody-positive CIDP who underwent sural nerve biopsies. RESULTS: All patients were relatively young at onset. Three patients experienced tremors, and 2 patients had severe ataxia. Although the response to intravenous immunoglobulin was poor in all patients, plasma exchange and corticosteroids were at least partially effective. Immunoadsorption plasmapheresis was performed in 1 patient but was ineffective. Electron microscopic examination of sural nerve biopsies revealed loss of paranodal transverse bands in all patients. DISCUSSION: Anti-NF155 IgG4 antibody-positive CIDP shows distinctive clinicopathological features, indicating that the IgG4 antibody is directly associated with the pathogenic mechanisms of anti-NF155 IgG4 antibody-positive CIDP. Muscle Nerve 57: 498-502, 2018.
Assuntos
Corticosteroides/uso terapêutico , Moléculas de Adesão Celular/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores de Crescimento Neural/imunologia , Troca Plasmática , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Adulto , Autoanticorpos/sangue , Feminino , Humanos , Masculino , Microscopia Eletrônica , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Resultado do Tratamento , Adulto JovemAssuntos
Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Doenças Desmielinizantes/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/efeitos adversos , Polineuropatias/induzido quimicamente , Doença Aguda , Idoso , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/fisiopatologia , Doenças Desmielinizantes/terapia , Diagnóstico Diferencial , Síndrome de Guillain-Barré/diagnóstico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Condução Nervosa , Polineuropatias/diagnóstico , Polineuropatias/fisiopatologia , Polineuropatias/terapiaRESUMO
A series of artemisinin-indoloquinoline hybrids were designed and synthesized in an attempt to develop potent and selective anti-tumor agents. Compounds 7a-7f, 8 and 9 were prepared and characterized. Their antiproliferative activities against MV4-11, HCT-116, A549, and BALB/3T3 cell lines in vitro were tested. Nearly all of the tested compounds (7-9, except for compounds 7d and 7e against HCT-116) showed an increased antitumor activity against HCT-116 and A549 cell lines when compared to the dihydroartemisinin control. Especially for the artemisinin-indoloquinoline hybrid 8, with an 11-aminopropylamino-10H-indolo[3,2-b]quinoline substituent, the antiproliferative activity against the A549 cell line had improved more than ten times. The IC50 value of hybrid 8 against A549 cell lines was decreased to 1.328 ± 0.586 µM, while dihydroartemisin showed IC50 value of >20 µM in the same cell line. Thus, these results have proven that the strategy of introducing a planar basic fused aromatic moiety, such as the indoloquinoline skeleton, could improve the antiproliferative activity and selectivity towards cancer cell lines.