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3.
Toxins (Basel) ; 10(7)2018 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-30002351

RESUMO

Anthrax caused by Bacillus anthracis is a lethal infectious disease, especially when inhaled, and the mortality rate approaches 100% without treatment. The anthrax antitoxin monoclonal antibody (MAb) 5E11 is a humanized antibody that targets the anthrax protective antigen (PA). The efficacy of 5E11 needs proper animal models. However, anthrax spores are extremely dangerous, so experiments must be conducted under Biosafety Level 3 conditions. Considering the critical effects of lethal toxin (LT) on hosts during infection, we report the establishment of a LT-challenged rabbit model, which caused 100% mortality with a dose of 2 mg PA + 1 mg LF, while a 4 mg PA + 2 mg LF challenge could limit death to within three days. Then, we evaluated 5E11 efficacy against LT. A prophylactic study showed that the i.v. administration of 40 mg/kg 5E11 four days before lethal dose LT challenge could lead to 100% survival. In therapeutic studies, the i.v. administration of 40 mg/kg 5E11 10 min after lethal dose LT challenge could provide complete protection. Overall, we developed a new LT-challenged rabbit model, and our results indicate that 5E11 shows potential for the clinical application in anthrax treatment.


Assuntos
Anticorpos Monoclonais/farmacologia , Antígenos de Bactérias/toxicidade , Toxinas Bacterianas/toxicidade , Modelos Animais de Doenças , Animais , Antraz/tratamento farmacológico , Citocinas/sangue , Feminino , Coelhos
4.
Surgery ; 162(2): 408-417, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28624177

RESUMO

BACKGROUND: The present study was designed to examine the effect of autophagy and apoptosis on intestinal injury in mice after severe burns. METHODS: Kunming mice were subjected to third degree burns over 30% of the total body surface area. Damage to the intestine was assessed by examining changes in intestinal mucosal morphology, enzyme-linked immunosorbent assay of serum d-lactate, diamine oxidase, lipopolysaccharide, interleukin-6, and tumor necrosis factor α (marker of intestinal damage), hematoxylin and eosin staining, and Western blotting under 4 experimental conditions: control group, burn only (burn group), burn and administration of rapamycin to stimulate intestinal autophagy (rapamycin group), or burn and administration of 3-methyladenine to inhibit intestinal autophagy (3-methyladenine group). RESULTS: At day 1 postburn, the expression levels of light chain 3 II, beclin-1, and cleaved caspase-3 were significantly greater in all 3 groups of mice subjected to the burn injury than in the control group 1 day postburn; while the levels of light chain 3 II and beclin-1 were significantly greater and those of cleaved caspase-3 were significantly less in the rapamycin group than in the burn group. In contrast, light chain 3 II and beclin-1 levels were significantly less and those of cleaved caspase-3 significantly greater in the 3-methyladenine group. All 3 groups subjected to burn injury showed significantly increased levels of d-lactate, diamine oxidase, lipopolysaccharide, interleukin-6, and tumor necrosis factor α. Of the 3 groups, the rapamycin group exhibited the least observed levels, the 3-methyladenine group the greatest, and the burn group intermediate. Pathologic sections of the intestinal tissue showed that all 3 burn groups exhibited severe intestinal mucosal damage at 1 day postburn. The condition of the 3-methyladenine treatment group was worse than that of the rapamycin treatment group, but better than that of the burn group. CONCLUSION: Intestinal autophagy is activated in response to intestinal apoptosis after severe burns and may alleviate burn-induced intestinal injury.


Assuntos
Autofagia , Queimaduras/patologia , Intestinos/patologia , Adenina/análogos & derivados , Animais , Modelos Animais de Doenças , Feminino , Interleucina-6/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Sirolimo , Fator de Necrose Tumoral alfa/metabolismo
5.
Neurosci Lett ; 349(3): 209-11, 2003 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-12951205

RESUMO

To investigate the possible involvement of the transferrin (TF) gene polymorphism in the manifestation of Alzheimer's disease (AD), we analyzed the TF and apolipoprotein E (APOE) genotypes of 67 sporadic late-onset AD patients and 131 normal elderly controls in the Chinese population. Our data showed that the TF C1 homozygosity carriers had an increased risk of AD in subjects > or =75 years of age, showing that homozygosity for the TF C1 allele was associated with an approximately three-fold increased risk (OR=3.57, 95% CI, 1.24-10.27, P=0.014). No synergic effects were found between the APOE epsilon 4 allele and TF gene polymorphisms.


Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Química Encefálica/genética , Encéfalo/metabolismo , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Transferrina/genética , Fatores Etários , Idoso , Doença de Alzheimer/metabolismo , Apolipoproteína E4 , Encéfalo/fisiopatologia , China/etnologia , Análise Mutacional de DNA , Feminino , Frequência do Gene/genética , Testes Genéticos , Genótipo , Humanos , Masculino , Fatores de Risco
6.
Yi Chuan Xue Bao ; 29(11): 949-52, 2002.
Artigo em Chinês | MEDLINE | ID: mdl-12645255

RESUMO

Secretor gene (FUT2)-encoded secretor type alpha(1,2)-fucosyltransferase (Se enzyme) that regulates expression and secretion of ABO(H) antigens in epithelial cell of glands and body fluids. It has the extensive polymorphism and race specificity. In the present study, we investigated the distribution of the fusion gene of the FUT2 locus in 191 Manchu individuals from Liaoning Province and 208 Mongolian individuals from Inner Mongolia, and analyzed the polymorphism of the FUT2 gene in 90 unrelated Han Chinese from Shandong Province and 90 Mongolian from Inner Mongolia, respectively. The fusion gene was not found in the two investigated ethnic groups. The frequencies of G849A nonsense mutation in Shandong Han Chinese and Mongolian of Inner Mongolia individuals were the same, 0.0055.


Assuntos
Fucosiltransferases/genética , Polimorfismo Genético , China , DNA/genética , DNA/metabolismo , DNA-Citosina Metilases/metabolismo , Desoxirribonucleases de Sítio Específico do Tipo II/metabolismo , Frequência do Gene , Humanos , Mutação , Polimorfismo de Fragmento de Restrição , Galactosídeo 2-alfa-L-Fucosiltransferase
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