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2.
Mar Drugs ; 12(7): 4086-95, 2014 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-25003792

RESUMO

Enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. No vaccine or antiviral therapy is currently available. In this work, we found that the number of B cells was reduced in enterovirus 71-infected mice. Deferoxamine, a marine microbial natural product, compensated for the decreased levels of B cells caused by enterovirus 71 infection. The neutralizing antibody titer was also improved after deferoxamine treatment. Furthermore, deferoxamine relieved symptoms and reduced mortality and muscle damage caused by enterovirus 71 infection. This work suggested that deferoxamine has the potential for further development as a B cell-immunomodulator against enterovirus 71.


Assuntos
Linfócitos B/efeitos dos fármacos , Desferroxamina/uso terapêutico , Enterovirus Humano A , Infecções por Enterovirus/tratamento farmacológico , Animais , Desferroxamina/farmacologia , Infecções por Enterovirus/imunologia , Infecções por Enterovirus/mortalidade , Camundongos , Carga Viral
3.
Virol J ; 10: 215, 2013 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-23809248

RESUMO

BACKGROUND: Enterovirus 71 (EV71) infections are associated with a high prevalence of hand, foot and mouth disease (HFMD) in children and occasionally cause lethal complications. Most infections are self-limiting. However, resulting complications, including aseptic meningitis, encephalitis, poliomyelitis-like acute flaccid paralysis, and neurological pulmonary edema or hemorrhage, are responsible for the lethal symptoms of EV71 infection, the pathogenesis of which remain to be clarified. RESULTS: In the present study, 2-week-old Institute of Cancer Research (ICR) mice were infected with a mouse-adapted EV71 strain. These infected mice demonstrated progressive paralysis and died within 12 days post infection (d.p.i.). EV71, which mainly replicates in skeletal muscle tissues, caused severe necrotizing myositis. Lesions in the central nervous system (CNS) and other tissues were not observed. CONCLUSIONS: Necrotizing myositis of respiratory-related muscles caused severe restrictive hypoventilation and subsequent hypoxia, which could explain the fatality of EV71-infected mice. This finding suggests that, in addition to CNS injury, necrotic myositis may also be responsible for the paralysis and death observed in EV71-infected mice.


Assuntos
Enterovirus Humano A/fisiologia , Infecções por Enterovirus/patologia , Interações Hospedeiro-Patógeno , Hipoventilação , Miosite/patologia , Miosite/virologia , Animais , Morte , Modelos Animais de Doenças , Infecções por Enterovirus/complicações , Infecções por Enterovirus/virologia , Hipóxia , Camundongos Endogâmicos ICR , Miosite/complicações , Paralisia
4.
Int J Mol Sci ; 14(5): 9618-27, 2013 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-23644889

RESUMO

Human enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. Presently, no vaccines or antiviral drugs have been clinically available to employ against EV71. In this study, we demonstrate that treatment with chebulagic acid reduced the viral cytopathic effect on rhabdomyosarcoma cells with an IC50 of 12.5 µg/mL. The utilization of the chebulagic acid treatment on mice challenged with a lethal dose of enterovirus 71 was able to efficiently reduce mortality and relieve clinical symptoms through the inhibition of viral replication. Chebulagic acid may represent a potential therapeutic agent to control infections to enterovirus 71.


Assuntos
Antivirais/uso terapêutico , Benzopiranos/uso terapêutico , Enterovirus Humano A/efeitos dos fármacos , Infecções por Enterovirus/tratamento farmacológico , Glucosídeos/uso terapêutico , Taninos Hidrolisáveis/uso terapêutico , Animais , Linhagem Celular , Enterovirus Humano A/fisiologia , Infecções por Enterovirus/patologia , Humanos , Camundongos , Replicação Viral/efeitos dos fármacos
5.
Molecules ; 17(9): 10370-6, 2012 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-22932217

RESUMO

Human enterovirus 71, a member of the Picornaviridae family, is one of the major causative agent of hand, foot and mouth disease in children less than six years old. This illness has caused mortalities in large-scale outbreaks in the Asia-Pacific region in recent years. No vaccine or antiviral therapy is available. In this study, antiviral effect of matrine against enterovirus 71 were evaluated in vitro and in vivo. Matrine could suppress the viral RNA copy number on rhabdomyosarcoma cells. Moreover, matrine treatment of mice challenged with a lethal dose of enterovirus 71 reduced the mortality and relieved clinical symptoms. The results showed that matrine may represent a potential therapeutic agent for enterovirus 71 infection.


Assuntos
Alcaloides/farmacologia , Antivirais/farmacologia , Enterovirus Humano A/efeitos dos fármacos , Enterovirus Humano A/genética , Doença de Mão, Pé e Boca/tratamento farmacológico , Quinolizinas/farmacologia , RNA Viral/análise , Alcaloides/uso terapêutico , Animais , Antivirais/uso terapêutico , Linhagem Celular , Doença de Mão, Pé e Boca/prevenção & controle , Doença de Mão, Pé e Boca/virologia , Humanos , Camundongos , Quinolizinas/uso terapêutico , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Matrinas
6.
Arch Pharm (Weinheim) ; 342(1): 34-40, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19072766

RESUMO

A series novel of N-(2-hydroxyethyl)amide derivatives was synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test (Tox). The maximal electroshock test showed that N-(2-hydroxyethyl)decanamide 1g, N-(2-hydroxyethyl)palmitamide 1l, and N-(2-hydroxyeth-yl)stearamide 1n were found to show a better anticonvulsant activity and also had lower toxicity than the marked anti-epileptic drug valproate. In the anti-MES potency test, these compounds exhibited median effective doses (ED50) of 22.0, 23.3, 20.5 mg/kg, respectively, and median toxicity doses (TD50) of 599.8, >1000, >1000 mg/kg, respectively, resulting in a protective index (PI) of 27.5, >42.9, >48.8, respectively. This is a much better protective index than that of the marked anti-epileptic drug valproate (PI = 1.6). To further investigate the effects of the anticonvulsant activity in several different models, compounds 1g, 1l, and 1n were tested having evoked convulsions with chemical substances, including pentylenetetrazloe, isoniazide, 3-mercaptopropionic acid, bicuculline, thiosemicarbazide, and strychnine.


Assuntos
Amidas/síntese química , Anticonvulsivantes/síntese química , Amidas/farmacologia , Amidas/toxicidade , Animais , Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Anticonvulsivantes/toxicidade , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Camundongos , Síndromes Neurotóxicas/etiologia , Convulsões/tratamento farmacológico , Convulsões/etiologia , Relação Estrutura-Atividade
7.
Yi Chuan ; 30(5): 655-8, 2008 May.
Artigo em Zh | MEDLINE | ID: mdl-18487158

RESUMO

In order to explore the educational model of combined research aidding basic medical education and clinical practice, the educational form of combined research, teaching and clinical practice was adopted and brought into the education of medical genetics for medical students. The consequence of five-year educational practice has revealed that the educational effects and quality have been obviously increased, and the deeply activated studying initiative, self-studying ability, ability of cooperation, discovering and creative ability have been achieved in culturing practical general medical students with in-depth basic knowledge, great ability and high quality.


Assuntos
Educação Médica/métodos , Educação Médica/normas , Educação de Graduação em Medicina/métodos , Educação de Graduação em Medicina/normas , Modelos Educacionais , Aprendizagem Baseada em Problemas/métodos , Aprendizagem Baseada em Problemas/normas
8.
Phytomedicine ; 20(1): 67-70, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-23146421

RESUMO

Human enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children and has caused mortalities in large-scale outbreaks in the Asia-Pacific region in recent years. No vaccine or antiviral therapy is available currently in the clinic. In this work, we investigated the antiviral effect of punicalagin on enterovirus 71 both in vitro and in vivo. The results showed that punicalagin reduced the viral cytopathic effect on rhabdomyosarcoma cells with an IC50) value of 15 µg/ml. Moreover, punicalagin treatment of mice challenged with a lethal dose of enterovirus 71 resulted in a reduction of mortality and relieved clinical symptoms by inhibiting viral replication. Our work suggested that punicalagin have the potential for further development as antiviral agents against enterovirus 71.


Assuntos
Antivirais/uso terapêutico , Enterovirus Humano A , Infecções por Enterovirus/tratamento farmacológico , Taninos Hidrolisáveis/uso terapêutico , Lythraceae/química , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Antivirais/farmacologia , Linhagem Celular Tumoral , Efeito Citopatogênico Viral/efeitos dos fármacos , Infecções por Enterovirus/mortalidade , Infecções por Enterovirus/virologia , Febre Aftosa/tratamento farmacológico , Febre Aftosa/virologia , Humanos , Taninos Hidrolisáveis/farmacologia , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/farmacologia , Replicação Viral/efeitos dos fármacos
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