RESUMEN
Sclerosing mesenteritis (SM) is a rare disease characterized by chronic nonspecific mesenteric inflammation and fibrosis of unknown etiology. Some tumefactive SM shows diffuse accumulation of IgG4-positive plasma cells and is considered as a part of the spectrum of IgG4-related disease. An association between inflammatory bowel disease and IgG4-related disease has been indicated. A 45-year-old woman visited our hospital due to weight loss with intermittent lower abdominal discomfort. Pelvic ultrasound revealed a mass-like lesion in the abdominal wall and pelvis MRI demonstrated a 5.9 cm sized wall-enhancing mass with heterogeneous signal intensity from right adnexa to the abdominal wall. Tumor resection and adhesiolysis was done because of severe adhesion with the small bowel, colon, bladder, uterus, and abdominal wall. Appendectomy was also performed due to adhesion and edematous change. Histological examination of the resected mass showed findings that were compatible with IgG4-related SM. The resected appendix showed chronic granulomatous inflammation without evidence of tuberculosis. She was diagnosed with Crohn's disease after undergoing colonoscopy and CT enterography. Herein, we report a rare case of IgG4-related SM that occurred in conjunction with Crohn's disease.
Asunto(s)
Enfermedad de Crohn/diagnóstico , Inmunoglobulina G/sangre , Paniculitis Peritoneal/diagnóstico , Antiinflamatorios/uso terapéutico , Apéndice/patología , Azatioprina/uso terapéutico , Colonoscopía , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Femenino , Humanos , Imagen por Resonancia Magnética , Mesalamina/uso terapéutico , Persona de Mediana Edad , Paniculitis Peritoneal/diagnóstico por imagen , Paniculitis Peritoneal/etiología , Prednisolona/uso terapéutico , Tomografía Computarizada por Rayos X , Ultrasonografía , Vejiga Urinaria/patologíaRESUMEN
It has been reported that the selective inhibitors of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) have considerable potential for treating type 2 diabetes mellitus, metabolic syndrome and inflammation. In the present study, we investigated the anti-diabetic and anti-inflammatory effects of N-(5-carbamoyladamantan-2-yl)-3-((2-fluorophenyl) sulfonyl)thiazolidine-2-carboxamide (KR-67105), a novel 11ß-HSD1 inhibitor, in diabetic mice model and preadipocyte model. KR-67105 concentration dependently inhibited 11ß-HSD1 activity in human and mouse 11ß-HSD1 overexpressing cells and mouse 3T3-L1 adipocytes. Furthermore, KR-67105 concentration-dependently inhibited 11ß-HSD1 activity in the ex vivo assay of C57BL/6 mice. In the study with diet-induced obese (DIO) mice, the administration of KR-67105 (100mg/kg/day, orally for 28 days) improved the glucose tolerance and insulin sensitivity as determined by the oral glucose tolerance test and the insulin tolerance test. Anti-diabetic effect by KR-67105 was associated with the suppression of diabetic related genes expression in liver and fat. Furthermore, KR-67105 suppressed 11ß-HSD1 activity in liver and fat of diabetic mice, but showed no effect on adrenal grand weight/body weight ratio and plasma corticosterone concentration in diabetic mice. In 3T3-L1 preadipocytes, cortisone induced the mRNA of inflammatory cytokines and 11ß-HSD1 and reactive oxygen species formation. This effect was abolished by co-incubation with KR-67105 in a concentration-dependent manner. Moreover, KR-67105 attenuated cortisone induced iNOS expression and phosphorylation of NF-κB p65, p38 MAPK, and ERK1/2 in preadipocytes. Taken together, it is concluded that a selective 11ß-HSD1 inhibitor, KR-67105, may provide a new therapeutic window in the prevention and treatment of type 2 diabetes with chronic inflammation without toxicity.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Antiinflamatorios/farmacología , Dieta/efectos adversos , Hipoglucemiantes/farmacología , Obesidad/tratamiento farmacológico , Tiazolidinas/farmacología , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/química , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/patología , Animales , Antiinflamatorios/metabolismo , Antiinflamatorios/uso terapéutico , Cortisona/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Humanos , Hipoglucemiantes/metabolismo , Hipoglucemiantes/uso terapéutico , Hipotálamo/efectos de los fármacos , Hipotálamo/fisiopatología , Resistencia a la Insulina , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Obesos , Modelos Moleculares , Obesidad/metabolismo , Obesidad/patología , Obesidad/fisiopatología , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/fisiopatología , Conformación Proteica , Tiazolidinas/metabolismo , Tiazolidinas/uso terapéuticoRESUMEN
BACKGROUND/AIMS: Colonoscopic polypectomy is a valuable procedure for preventing colorectal cancer, but is not without complications. Delayed bleeding after colonoscopic polypectomy is a rare, but serious complication. The aim of this study was to identify risk factors of delayed bleeding after colonoscopic polypectomy. METHODS: A retrospective case-control study was conducted in a single university hospital. Forty cases and 120 controls were included. Data collected included comorbidity, use of antiplatelet agents, size and number of resected polyps, histology and gross morphology of resected polyps, endoscopist's experience, resection method, use of sedation, and use of prophylactic hemostasis. RESULTS: In univariate analysis, size, histology and number of resected polyps, endoscopist's experience, resection method and use of prophylactic hemostasis were significant risk factors for delayed bleeding after colonoscopic polypectomy. In multivariate analysis, risk of delayed bleeding increased by 11.6% for every 1 mm increase in resected polyp diameter (OR, 1.116; 95% CI 1.041-1.198; p=0.002). Number of resected polyps (OR, 1.364; 95% CI, 1.113-1.671; p=0.003) and endoscopist's experience (OR, 6.301; 95% CI, 2.022-19.637; p=0.002) were significant risk factors for delayed bleeding after colonoscopic polypectomy. CONCLUSIONS: Size and numbers of resected polyps, and endoscopist's experience were independent risk factors for delayed bleeding after colonoscopic polypectomy. More caution would be necessary when removing polyps with these factors.
Asunto(s)
Enfermedades del Colon/diagnóstico , Pólipos del Colon/cirugía , Hemorragia Gastrointestinal/etiología , Adulto , Anciano , Estudios de Casos y Controles , Enfermedades del Colon/patología , Colonoscopía/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Posoperatoria/etiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Carbenoxolone is the 3-hemisuccinate of glycyrrhetinic acid, the active principal of licorice (Glycyrrhiza glabra). It was reported that carbenoxolone improved glucose tolerance with increased insulin sensitivity in mice with high fat diet-induced obesity. In the present study, we elucidated the protective effect of carbenoxolone in fatty liver animal models of C57BL/6-Lep(ob/ob) mice through inhibition of hepatic lipogenesis and apoptosis. In addition, the potential mechanisms by which carbenoxolone could exert such protection were elucidated. Carbenoxolone was daily administrated by gavage for 28 days in C57BL/6 and C57BL/6-Lep(ob/ob) mice. Carbenoxolone prevented the plasma triglyceride and free fatty acid accumulation associated with the reduction of the expression of sterol regulatory element binding protein-1c, liver X receptor, fatty acid synthase and acethyl-CoA carboxylase in the livers of C57BL/6-Lep(ob/ob) mice. Carbenoxolone also prevented hepatic injury through anti-apoptotic action in the livers of C57BL/6-Lep(ob/ob) mice, accompanied by increased Bcl-2 expression and suppressed Bax and cytochrome c expression. As a mechanism, increased inflammatory cytokine expressions were inhibited by carbenoxolone in the fatty livers of C57BL/6-Lep(ob/ob) mice. Furthermore, carbenoxolone inhibited free fatty acid (oleate/palmitate) induced reactive oxygen species formation and reversed free fatty acid induced mitochondrial membrane depolarization in HepG2 cells. Carbenoxolone prevents the development of fatty liver by inhibiting sterol regulatory element binding protein-1c expression and activity with an anti-apoptotic mechanism via the inhibition of inflammatory cytokine and reactive oxygen species formation in the livers of C57BL/6-Lep(ob/ob) mice. It is suggested that carbenoxolone prevents the development and progression of fatty liver disease in patients with insulin resistance.