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In kidney transplantation acute allograft rejection is the most common cause of late allograft loss. Changes in indoleamine 2,3 dioxygenase (IDO) activity, which catabolizes the degradation of tryptophan to kynurenine, may predict rejection. However, exogenous IDO is immunosuppressive in rodent kidney transplantation. Thus, the increase in IDO activity observed in acute allograft rejection is insufficient to prevent rejection. To address this question, we assessed the regulation of IDO and its role in acute rejection in a porcine model of kidney transplant. In tissue samples from rejecting kidney allografts, we showed a 13-fold increase in IDO gene transcription and 20-fold increase in IDO enzyme activity when compared with autotransplanted kidneys. Allografts also demonstrated an over fourfold increase in tissue interferon (IFN)-γ, with marked increases in tumor necrosis factor (TNF)-α, TNF-β and interleukin 1β. Gene transcription and protein levels of kynurenine 3-monooxygenase (KMO) were decreased. KMO generates the immunosuppressive kynurenine, 3-hydroxykynurenine. The results of these studies demonstrate a clear association between rejection and increased allograft IDO expression, likely driven in part by IFN-γ and facilitated by other cytokines of the allogeneic response. Moreover, the loss of downstream enzymatic activity in the IDO metabolic pathway may suggest novel mechanisms for the perpetuation of rejection.

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This study was conducted to assess whether race and socioeconomic status influence the management method used to treat pediatric perforated appendicitis. Nonelective pediatric admissions with a primary diagnosis of appendicitis were analyzed using data from the 2001–2010 Nationwide Inpatient Sample. Bivariate and multivariate analyses were used to determine the association between race, insurance status, median household income, rural/metropolitan location, and the risk adjusted odds of undergoing surgery, laparoscopic appendectomy, percutaneous drainage, or neither surgery nor percutaneous drainage. A total of 46,211 admissions of perforated appendicitis were identified. Surgery was performed in 90.5 per cent of them. Black children were less likely to have surgery [adjusted odds ratio (AOR) = 0.53] and more likely to be managed non-surgically with percutaneous drainage (AOR = 1.79). Self-pay patients were less likely to have laparoscopic surgery (AOR = 0.80). Children from rural counties were more likely to undergo surgery than those from larger metropolitan areas (AOR = 1.30). Higher estimated household income did not predict the method of treatment. Although previous studies have attributed racial disparities in outcomes for appendicitis to different rates of perforation and access to care, these findings demonstrate significantly dissimilar management strategies for patients presenting with a similar disease process.