Acid sphingomyelinase (aSMase) plays an important role in endothelial dysfunction. Here, we show that elevated aSMase activity and ceramide content were reduced by desipramine treatment in diabetic animals. The inhibitor of aSMase, desipramine, improved vascular dysfunction in db/db mice. High glucose (HG)-induced up-regulation of aSMase activity and ceramide levels were restored by treatment with aSMase siRNA or desipramine in endothelial cells. In addition, aSMase siRNA or desipramine treatment increased the release of nitric oxide (NO) and the phosphorylation of endothelial NO synthase (eNOS) in diabetic mouse aortas and aortic endothelial cells with HG. These results indicate that inhibition of aSMase/ceramide pathway improves endothelium-dependent vascular relaxation (EDR) largely through regulating the eNOS/NO pathway in diabetic animals.
Diabetic vascular complications are the leading causes of death and disability in patients with diabetes. Alpha‐mangostin has been reported to have anti‐diabetic capacity in recent years. Here, we investigated the protective function of alpha‐mangostin on endothelium in vitro and in vivo experiments. We also observed that alpha‐mangostin improved impaired endothelium‐dependent vasodilation (EDV) of diabetic animals while it limited the aSMase/ceramide pathway and up‐regulated eNOS/NO pathway in aortas from diabetic mice. Meanwhile, alpha‐mangostin inhibited elevated aSMase/ceramide pathway and reversed impaired EDV induced by high glucose in isolated mouse aortas. In addition, alpha‐mangostin increased phosphorylation of eNOS and NO production in high glucose‐treated aortas. Alpha‐mangostin normalized high glucose‐induced activation of aSMase/ceramide pathway and improved eNOS/NO pathway in endothelial cells with high glucose. In conclusion, alpha‐mangostin regulates eNOS/NO pathway and improves EDV in aortas of diabetic mice through inhibiting aSMase activity and endogenous ceramide accumulation.
Objectives To investigate the association of hiatal area (HA), bladder neck mobility, and urethral mobility during the cough stress test (CST) with stress urinary incontinence (SUI). Methods This was a prospective study of 110 continent and 190 incontinent women using transperineal ultrasound. HA, bladder neck mobility, and the mobility of six points along the urethra (Vectors 1–6) were measured. The cohort was randomly divided at a ratio of 2:1 into a training cohort and a validation cohort. The correlations of HA with bladder neck mobility, urethral mobility, and SUI were tested. The predictive model was yielded by fisher linear discriminant analysis and receiver operating characteristics to assess the parameters' ability to predict SUI. Results Valid data were collected from 177 incontinent women and 105 continent women. Significant differences were identified in HA, body mass index (BMI), funneling, bladder neck mobility, and Vectors 1–6 between them. HA was positively correlated to bladder neck mobility. In the training cohort, bladder neck position on Valsalva, Vectors 3, and BMI had the area under curves of 0.74, 0.69, and 0.66 (all P < 0.001); Funneling and Vector 3 had odds ratios of 18.96 and 3.65 (all P < 0.001), for predicting SUI. The predictive model incorporating funneling, Vectors 3, and BMI provided the best performance in predicting SUI in both cohorts. Conclusion The larger the HA was, the higher the bladder neck mobility. However, it was mid‐urethral mobility rather than bladder neck mobility that performed best at predicting SUI.
Objectives-To describe the urethral mobility during urine leaking in stress urinary incontinence (SUI) by transperineal ultrasound (TPUS) with urethral mobility profile (UMP) analysis.Methods-This was a prospective study of 380 women who had a cough stress test (CST) with TPUS. UMP software automatically placed six equidistant points from the bladder neck (Point 1) to the external urethral meatus (Point 6) and determined their x and y coordinates relative to the symphysis pubis. Urethral mobility vector of Points 1-6 (Vectors 1-6) and the distance between the six points and the symphysis (Dist. 1-6) were calculated and compared between the two groups. The visualized UMP was created by reproducing the positions of the six points at rest and on Valsalva.Results-Valid data of 188 women with SUI and 174 continent women were analyzed. The mean age of all 362 women was 49.3 years. Mean body mass index in the SUI group was significantly increased (23.8 vs 22.2 kg/m 2 , P < .001). During CST, Vectors 1-6 and Dist. 2-6 were significantly increased (all P < .005) in the SUI group. The UMP showed the mid-urethral rotated down around the symphysis pubis. The upper urethral profile in the two groups was similar. But the gap between the mid-urethra and the symphysis was wider in the SUI group.Conclusions-The visualized UMP illustrated the mid-urethral hypermobility in SUI by showing a wider gap due to the unstable connection between the mid-urethra and the symphysis pubis.
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