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1.
Cell Mol Gastroenterol Hepatol ; 7(2): 339-355, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30704983

RESUMO

BACKGROUND & AIMS: Hypoxia-associated pathways influence the development of inflammatory bowel disease. Adaptive responses to hypoxia are mediated through hypoxia-inducible factors, which are regulated by iron-dependent hydroxylases. Signals reflecting oxygen tension and iron levels in enterocytes regulate iron metabolism. Conversely, iron availability modulates responses to hypoxia. In the present study we sought to elucidate how iron influences the responses to hypoxia in the intestinal epithelium. METHODS: Human subjects were exposed to hypoxia, and colonic biopsy specimens and serum samples were collected. HT-29, Caco-2, and T84 cells were subjected to normoxia or hypoxia in the presence of iron or the iron chelator deferoxamine. Changes in inflammatory gene expression and signaling were assessed by quantitative polymerase chain reaction and Western blot. Chromatin immunoprecipitation was performed using antibodies against nuclear factor (NF)-κB and primers for the promoter of tumor necrosis factor (TNF) and interleukin (IL)1ß. RESULTS: Human subjects presented reduced levels of ferritin in the intestinal epithelium after hypoxia. Hypoxia reduced iron deprivation-associated TNF and IL1ß expression in HT-29 cells through the induction of autophagy. Contrarily, hypoxia triggered TNF and IL1ß expression, and NF-κB activation in Caco-2 and T84 cells. Iron blocked autophagy in Caco-2 cells, while reducing hypoxia-associated TNF and IL1ß expression through the inhibition of NF-κB binding to the promoter of TNF and IL1ß. CONCLUSIONS: Hypoxia promotes iron mobilization from the intestinal epithelium. Hypoxia-associated autophagy reduces inflammatory processes in HT-29 cells. In Caco-2 cells, iron uptake is essential to counteract hypoxia-induced inflammation. Iron mobilization into enterocytes may be a vital protective mechanism in the hypoxic inflamed mucosa.


Assuntos
Hipóxia/complicações , Inflamação/tratamento farmacológico , Inflamação/etiologia , Mucosa Intestinal/metabolismo , Ferro/uso terapêutico , NF-kappa B/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Autofagia/efeitos dos fármacos , Células CACO-2 , Células HT29 , Humanos , Inflamação/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Pessoa de Meia-Idade , Modelos Biológicos , Regiões Promotoras Genéticas/genética , Estabilidade de RNA/efeitos dos fármacos , Estabilidade de RNA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
2.
BMJ Open Sport Exerc Med ; 4(1): e000270, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29387441

RESUMO

BACKGROUND: This article addresses typical injury patterns related to the traditional Swiss folk wrestling, 'Schwingen'. This is a fight between two competitors with its own rules, grips and throws. A variety of injuries have been occasionally reported. The aim of this study was to characterise all cases of Schwingen injuries treated in the University Hospital of Bern from January 2006 to July 2016. METHODS: To assess the frequency, type and outcome of Schwingen injuries, database search was performed of all inpatient and outpatient cases related to Schwingen that were admitted to Bern University Hospital from January 2006 to December 2016. RESULTS: A total of 32 such patients could be identified. Apart from a single woman, all patients were male. 31 of the 32 players were Swiss. One patient was admitted to the intermediate care unit, eight patients underwent surgery, two were hospitalised for further treatment and two were given a plaster. 17 other patients were given medications such as painkillers. One was dismissed without further treatment and another one left the hospital on his own. Typical injury patterns varied from simple lesions to distortions and fractures as well as head injuries and other neurological complications. CONCLUSION: The majority of injuries caused by Schwingen are not life threatening. Nevertheless, there is always the potential of head injuries and neurological deficits. Apart from the economic loss due to treatment costs and sick leave, these injuries can be disabling for life. It should therefore be obligatory for all players to evaluate preventive measures.

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