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1.
Epidemiol Infect ; 145(15): 3096-3105, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28946931

RESUMO

Psittacosis is a zoonotic infectious disease caused by the transmission of the bacterium Chlamydia psittaci from birds to humans. Infections in humans mainly present as community-acquired pneumonia (CAP). However, most cases of CAP are treated without diagnostic testing, and the importance of C. psittaci infection as a cause of CAP is therefore unclear. In this meta-analysis of published CAP-aetiological studies, we estimate the proportion of CAP caused by C. psittaci infection. The databases MEDLINE and Embase were systematically searched for relevant studies published from 1986 onwards. Only studies that consisted of 100 patients or more were included. In total, 57 studies were selected for the meta-analysis. C. psittaci was the causative pathogen in 1·03% (95% CI 0·79-1·30) of all CAP cases from the included studies combined, with a range between studies from 0 to 6·7%. For burden of disease estimates, it is a reasonable assumption that 1% of incident cases of CAP are caused by psittacosis.


Assuntos
Chlamydophila psittaci , Pneumonia Bacteriana/microbiologia , Psitacose/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Humanos , Pneumonia Bacteriana/epidemiologia
2.
Oncogene ; 36(24): 3397-3405, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27819675

RESUMO

Intestinal epithelial stem cells are highly sensitive to differentiation induced by endoplasmic reticulum (ER) stress. Colorectal cancer develops from mutated intestinal epithelial stem cells. The most frequent initiating mutation occurs in Apc, which results in hyperactivated Wnt signalling. This causes hyperproliferation and reduced sensitivity to chemotherapy, but whether these mutated stem cells are sensitive to ER stress induced differentiation remains unknown. Here we examined this by generating mice in which both Apc and ER stress repressor chaperone Grp78 can be conditionally deleted from the intestinal epithelium. For molecular studies, we used intestinal organoids derived from these mice. Homozygous loss of Apc alone resulted in crypt elongation, activation of the Wnt signature and accumulation of intestinal epithelial stem cells, as expected. This phenotype was however completely rescued on activation of ER stress by additional deletion of Grp78. In these Apc-Grp78 double mutant animals, stem cells were rapidly lost and repopulation occurred by non-mutant cells that had escaped recombination, suggesting that Apc-Grp78 double mutant stem cells had lost self-renewal capacity. Although in Apc-Grp78 double mutant mice the Wnt signature was lost, these intestines exhibited ubiquitous epithelial presence of nuclear ß-catenin. This suggests that ER stress interferes with Wnt signalling downstream of nuclear ß-catenin. In conclusion, our findings indicate that ER stress signalling results in loss of Apc mutated intestinal epithelial stem cells by interference with the Wnt signature. In contrast to many known inhibitors of Wnt signalling, ER stress acts downstream of ß-catenin. Therefore, ER stress poses a promising target in colorectal cancers, which develop as a result of Wnt activating mutations.


Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Neoplasias do Colo/genética , Células Epiteliais/citologia , Proteínas de Choque Térmico/genética , Células-Tronco/citologia , Animais , Diferenciação Celular , Proliferação de Células , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Células Epiteliais/metabolismo , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Transgênicos , Mutação , Células-Tronco/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo
3.
Arch Physiol Biochem ; 113(4-5): 173-85, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18158643

RESUMO

Insulin is an important regulator of hepatic carbohydrate, lipid, and protein metabolism, and the regulation of these processes by insulin is disturbed under conditions of insulin resistance and type 2 diabetes. Despite these alterations, the impact of insulin resistance on insulin signalling in the liver is not well defined. Variations in time and dose of insulin stimulation as well as plasma glucose levels may underlie this. The present study aimed at determining the dynamics of activation of hepatic insulin signalling in vivo at insulin concentrations resembling those achieved after a meal, and addressing the effects of high-fat feeding. An unexpected finding of this study was the biphasic activation pattern of the IRS-PI3K-PKB/Akt pathway. Our findings indicate that the first burst of activation contributes to regulation of glucose metabolism. The physiological function of the second peak is still unknown, but may involve regulation of protein synthesis. Finally, high-fat feeding caused hepatic insulin resistance, as illustrated by a reduced suppression of hepatic glucose production. A sustained increased phosphorylation of the serine/threonine kinases p70S6kinase and Jun N-terminal kinase in the absence of insulin may underlie the abrogated phosphorylation of the IRS proteins and their downstream targets.


Assuntos
Gorduras na Dieta/farmacologia , Técnica Clamp de Glucose , Hiperinsulinismo/metabolismo , Insulina/metabolismo , Fígado/metabolismo , Transdução de Sinais , Animais , Gorduras na Dieta/administração & dosagem , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Glucose/farmacologia , Insulina/sangue , Insulina/farmacologia , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor de Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos
4.
Acta Otorhinolaryngol Belg ; 54(3): 293-8, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11082765

RESUMO

In this article a review is presented of the morphology and function of respiratory cilia and emphasis is placed on the importance of mucociliary clearance as the most important defense mechanism of the upper and lower airways. Physical factors and pharmacological substances which can influence ciliary activity and mucociliary transport are mentioned. Finally, a description is given of changes, mostly reversible, of the mucociliary transport system in infections and IgE-mediated allergy and of the, irreversible changes in congenital diseases like cystic fibrosis and primary ciliary dyskinesia, with some remarks as to the therapeutical consequences of these disturbances.


Assuntos
Cílios/fisiologia , Anti-Infecciosos Locais/farmacologia , Infecções Bacterianas/complicações , Compostos de Benzalcônio/farmacologia , Cílios/efeitos dos fármacos , Cílios/imunologia , Transtornos da Motilidade Ciliar/etiologia , Transtornos da Motilidade Ciliar/imunologia , Transtornos da Motilidade Ciliar/fisiopatologia , Fibrose Cística/imunologia , Humanos , Umidade , Imunoglobulina E/imunologia , Depuração Mucociliar/efeitos dos fármacos , Depuração Mucociliar/fisiologia , Oxigênio/metabolismo , Mucosa Respiratória/fisiologia , Cloreto de Sódio/farmacologia , Temperatura
6.
Lung ; 168 Suppl: 320-6, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2117132

RESUMO

The Dutch Foundation on Smoking and Health is executor of the Dutch governmental information policy to discourage smoking. Although smoking prevalences have steadily decreased from 60% in 1967 to 33% in 1989, much needs to be done to continue to eliminate this dangerous habit. The main priority of the Foundation is to prevent young people from taking up the habit of smoking. To this end, we use two different education and prevention campaigns: 1) "Don't play with fire," a school program aimed at children 10-12 years old. It consists of a teachers manual and six worksheets for each pupil and gives information about seven different aspects of the smoking habit; 2) a continuing approach, via posters, advertisements in youth media and school materials to young adolescents 13-19 years old. In 1983 the campaign "I don't smoke, I play sports"; in 1986 "Smoking . . . why should I"; and in 1989 "Smoking? Why should you?" Both programs led to increased knowledge, changed attitudes, and decreased smoking habits among both target groups.


Assuntos
Atitude Frente a Saúde , Educação em Saúde/métodos , Prevenção do Hábito de Fumar , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Países Baixos/epidemiologia , Fumar/epidemiologia
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