ABSTRACT
Background: Preoperative evaluation of the dysganglionic bowel segment is critical for establishing the optimal resection strategy for Hirschsprung's disease (HSCR), which facilitates patient outcomes. Objective: We set out to determine the utility of the 24-h delayed film of barium retention in predicting the length of dysganglionic bowel segment in HSCR. Materials and methods: A retrospective study of patients with clinically suspicious HSCR who underwent a preoperative 24-h delayed film of barium enema and were surgically treated from January 2015 to December 2019 was conducted. Results: Two hundred and 58 patients were enrolled in this study. The sensitivity, specificity, positive and negative predictive values (NPVs) of the 24-h delayed film of barium enema to predict the neuropathological segment were 89.1, 91.5, 91.3, and 89.4%, respectively. The Youden index was 80.6%, with a kappa value of 0.806 (P < 0.001). The correlation rate between barium retention level and pathological results was 72.7% (16/22) when aganglionosis was restricted within the mid-distal rectum (short-segment type), increasing to 92.0% (46/50) and 93.5% (174/186) for patients that had aganglionosis extended beyond the mid-distal rectum (classical type) and sigmoid colon (long-segment type), respectively. Lastly, patients younger than 3 months showed a lower correlation rate (72.2%) compared to patients aged 3-12 months (91.0%) and > 12 months (92.6%). Conclusions: Our investigation of the 24-h delayed film of barium enema performed for patients suspected of having HSCR indicated that the barium retention level remains crucial in predicting dysganglionic bowel segment, which contributes to the decision-making for surgical physicians.
ABSTRACT
BACKGROUND: Previous studies have shown that oxidative stress contributes to hyperglycemia-induced erectile dysfunction. A preferential direct inhibitor of NOX1 and NOX4, GKT-137831, exhibited a strong antioxidative role via blockade of reactive oxygen species (ROS) generation in endothelial cells, but whether GKT-137831 could improve erectile function was not clear. AIM: Our study was designed to investigate the effect of NOX1/4 inhibition on improving diabetic erectile dysfunction (ED) in rats. METHODS: We used streptozotocin to induce type 1 diabetes mellitus (DM) in 32 male Sprague Dawley (SD) rats (8 weeks old). Eight weeks later, type 1 diabetes mellitus-induced erectile dysfunction (DMED) in rats was confirmed using an apomorphine test. Our study consisted of 3 groups: (i) nondiabetic control group (n = 8), (ii) DMED + vehicle group (DMED group; n = 8), and (iii) DMED + GKT-137831 group (n = 9); GKT-137831 was given as a once-daily intraperitoneal injection for 4 weeks. Cavernous nerve electrostimulation was used to evaluate erectile function. Western blot, ELISA, immunohistochemistry, and immunofluorescence were used to measure expression of specific proteins, and DHE fluorescent probe was performed to detect ROS level. OUTCOMES: Intracavernous pressure (ICP), nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway, oxidative stress level, inflammatory response, corporal autophagy, and apoptosis were measured. RESULTS: Erectile function in the DMED group was significantly impaired compared to the nondiabetic control group, whereas this impairment was improved with GKT-137831 treatment by 70%. Similarly, endothelial function and overactivated oxidative stress in the corpus cavernosum (CC) of the DMED + GKT-137831 group were improved. The DMED group showed serious inflammatory responses and excessive autophagy, which were inhibited by GKT-137831 treatment in the DMED + GKT-137831 group. CLINICAL TRANSLATION: Our study showed improvement in erectile function with GKT-137831 in a diabetic rat ED model. STRENGTH AND LIMITATIONS: This study suggested for the first time that GKT-137831, an NOX1/4 inhibitor undergoing clinical trials, is effective in improving erectile function in rats with type 1 DMED. However, we only investigated GKT-137831 treatment of streptozotocin-induced type 1 diabetic rats, and therapeutic evidence in other types of diabetes is lacking. CONCLUSION: GKT-137831 improves erectile function by 70% in type 1 DMED rats and constitutes a promising compound for the treatment of type 1 DMED, likely by inhibition of overactivated oxidative stress, down-regulation of proinflammatory factors, and amelioration of excessive autophagy and endothelial function. B Zhou, Y Chen, H Yuan, et al. NOX1/4 Inhibitor GKT-137831 Improves Erectile Function in Diabetic Rats by ROS Reduction and Endothelial Nitric Oxide Synthase Reconstitution. J Sex Med 2021;18:1970-1983.