Porcine intestinal lymphoid tissues synthesize estradiol

Estradiol (17β-estradiol) is synthesized primarily in the gonads of both sexes and regulates the development and function of reproductive organs. Recently, we reported that intestinal lymphocyte homeostasis is regulated by estradiol synthesized de novo in the endothelial cells of the high endothelial venules (HEVs) of mesenteric lymph nodes and Peyer's patches in mice. This observation prompted us to hypothesize that HEVs of intestinal lymphoid tissues are sites of estradiol synthesis across species. In this study, we examined whether estradiol is synthesized in the intestinal lymphoid tissues of adolescent piglets. Comparisons of estradiol levels in blood and tissue showed that estradiol concentrations in mesenteric lymph nodes and Peyer's patches were significantly higher than the level in serum. Reverse transcription polymerase chain reaction showed that porcine intestinal lymphoid tissues express mRNAs for steroidogenic enzymes (StAR, 17β-Hsd, 3β-Hsd, Cyp17a1, and Cyp19a1), and immunohistochemical results in ilial tissue showed expression of aromatase (CYP19) in Peyer's patch-localized endothelial cells of HEVs. When mesenteric lymph node and Peyer's patch tissues were cultured in vitro, they produced estradiol. Taken together, the results indicate that mesenteric lymph nodes and Peyer's patches are sites of estradiol synthesis in adolescent piglets.

A Rare Case of Free Bowel Perforation Associated with Infliximab Treatment for Stricturing Crohn's Disease / 대한소화기학회지

Crohn's disease is characterized by chronic transmural inflammation of the bowel and is associated with serious complications, such as bowel strictures, abscesses, fistula formation, and perforation. As neither medical nor surgical therapy provides a cure for Crohn's disease, the primary goals of therapy are to induce and maintain remission and prevent complications. As a biologic agent, infliximab, a monoclonal antibody to tumor necrosis factor, is indicated for refractory luminal and fistulizing Crohn's disease that does not respond to other medical therapies or surgery. Infliximab has proven to be very effective for inducing and maintaining remission in Crohn's disease; however, infliximab treatment has several potential complications. Here, we report a case of free perforation following a therapeutic response after an initial dose of infliximab for Crohn's disease. This is the first case report describing a free perforation in a Crohn's disease patient after an initial dose of infliximab.

How Should Azathioprine Be Dosed in Crohn's Disease? A Novel Strategy of Maximum Dose-titration Based on the Lower Limit of Leukocyte Count and Tolerability / 대한소화기학회지

BACKGROUND/AIMS: Although general guidelines have suggested weight-based dosing of azathioprine (AZA, 2.5 mg/kg/day) for Crohn's disease (CD), a substantial number of patients develop bone marrow suppression. The aim of this study was to evaluate the maximum dose of AZA not based on weight but titrated according to the lower limit of leukocyte count for maintaining remission in patients with CD. METHODS: Among a total of seventy-eight patients with CD, who had been followed-up at Kosin University Gospel Hospital (Busan, Korea) from 2010 to 2011, those treated with the maximum dose of AZA meeting both drug-tolerability and leukocytes count of more than 4,000/mm3 for steroid-free maintaining remission were enrolled. The titrated maximum AZA dose and its relationship with weight were evaluated. RESULTS: A total of 42 patients (male, 32 patients; mean age, 31 years) were enrolled. The maximum dose of AZA was 49.1 mg/day. The dose per weight was 0.87 mg/kg/day and negatively correlated with body weight (gamma=-0.51, p=0.01) and BMI (gamma=-0.33, p=0.034). AZA dose per weight in the below 40 years old group was significantly higher than that in the above 40 years old group (p=0.039). CONCLUSIONS: Dose decision of AZA based only on weight could put the patients to inappropriately low or high dose resulting in need of additional therapy or serious side effect, respectively. Therefore, the maximum dose-titration based on the lower limit of leukocyte count and tolerability is a novel and a valuable strategy in deciding the dose of thiopurines.