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1.
Cureus ; 15(1): e34089, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36843717

RESUMO

An otherwise healthy, 34-year-old man presented to the emergency department with abdominal pain, nausea, and vomiting, which began a day after he ingested a banana-stuffed condom. A contrast-enhanced computed tomography (CT) abdomen and pelvis revealed a dilated small bowel with a transition point, findings consistent with small bowel obstruction. Abdominopelvic ascites was also noted on imaging, which was concerning for bowel distress. He was taken to the operating room for an exploratory laparotomy, which revealed a high-grade obstruction by a foreign body, a banana stuffed in a condom, in the mid-jejunum. An enterotomy was performed to relieve the obstruction. The postoperative course was uneventful, and he was discharged three days later.

2.
J Clin Invest ; 129(2): 744-758, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640172

RESUMO

Goblet cell metaplasia, a disabling hallmark of chronic lung disease, lacks curative treatments at present. To identify novel therapeutic targets for goblet cell metaplasia, we studied the transcriptional response profile of IL-13-exposed primary human airway epithelia in vitro and asthmatic airway epithelia in vivo. A perturbation-response profile connectivity approach identified geldanamycin, an inhibitor of heat shock protein 90 (HSP90) as a candidate therapeutic target. Our experiments confirmed that geldanamycin and other HSP90 inhibitors prevented IL-13-induced goblet cell metaplasia in vitro and in vivo. Geldanamycin also reverted established goblet cell metaplasia. Geldanamycin did not induce goblet cell death, nor did it solely block mucin synthesis or IL-13 receptor-proximal signaling. Geldanamycin affected the transcriptome of airway cells when exposed to IL-13, but not when exposed to vehicle. We hypothesized that the mechanism of action probably involves TGF-ß, ERBB, or EHF, which would predict that geldanamycin would also revert IL-17-induced goblet cell metaplasia, a prediction confirmed by our experiments. Our findings suggest that persistent airway goblet cell metaplasia requires HSP90 activity and that HSP90 inhibitors will revert goblet cell metaplasia, despite active upstream inflammatory signaling. Moreover, HSP90 inhibitors may be a therapeutic option for airway diseases with goblet cell metaplasia of unknown mechanism.


Assuntos
Benzoquinonas/efeitos adversos , Células Caliciformes/metabolismo , Proteínas de Choque Térmico HSP90 , Interleucina-13/metabolismo , Interleucina-17/metabolismo , Lactamas Macrocíclicas/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Animais , Benzoquinonas/farmacologia , Células Caliciformes/patologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Lactamas Macrocíclicas/farmacologia , Masculino , Metaplasia , Camundongos
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