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Little is known about the early mechanisms mediating left ventricular (LV) diastolic dysfunction in patients with hereditary hemochromatosis (HH). However, the increased oxidative stress related to iron overload may be involved in this process, and strain rate (SR), a sensitive echocardiography derived measure of diastolic function, may detect such changes. Thus, we evaluated the relationship between left ventricular diastolic function measured with tissue Doppler SR and oxidative stress in asymptomatic HH subjects and control normal subjects. Ninety-four consecutive visits of 43 HH subjects, age 30 to 74 (50 ± 10, mean ± SD) and 37 consecutive visits of 21 normal volunteers age 30 to 63 (48 ± 8) were evaluated over a three-year period. SR was obtained from the basal septum in apical 4 chamber views. All patients had confirmed C282Y homozygosity, a documented history iron overload and were New York Heart Association functional class I. Normal volunteers lacked HFE gene mutations causing HH. In the HH subjects, the SR demonstrated moderate, but significant correlations with biomarkers of oxidative stress; however, no correlations were noted in normal subjects. The biomarkers of iron overload per se did not show significant correlations with the SR. Although our study was limited by the relatively small subject number, these results suggest that a possible role of oxidative stress to affect LV diastolic function in asymptomatic HH subjects and SR imaging may be a sensitive measure to detect that effect.

Oxidative stress (OXS) has been recently considered as one of anticancer strategies by taking advantage of higher vulnerability of cancer cells (than normal cells) to OXS. In fact, the successful outcomes using OXS have been reported in several cancer cases. A medicinal mushroom extract, PE isolated from Poria mushroom, has been shown to have anticancer/antitumor activity, although its anticancer mechanism has not been fully understood but may involve OXS. We investigated if PE might have anticancer effect on human bladder cancer cells through OXS in vitro. A dose-dependent (0-200 µg/ml of PE) study was first performed to assess cell viability using MTT assay. PE led to a significant reduction in cell viability with the IC 50 (50% inhibitory concentration) of 100 µg/ml. A possible anticancer role of OXS was then assessed by lipid peroxidation (LPO) assay. The results indicated that PE indeed exerted ~2.1-fold greater OXS (than controls) on the cells. The anticancer mechanism of PE was further explored, focusing on glycolysis, metabolic signaling pathways, and apoptosis. Two glycolytic parameters, hexokinase (HK) activity and cellular ATP level, have significantly declined, suggesting the inhibition of glycolysis. Coupled with the reduced ATP level, AMP-activated protein kinase (AMPK) was activated, while protein kinase B (Akt) was inactivated and concomitantly mammalian target of rapamycin (mTOR) was inhibited. These results imply the growth cessation, followed by cell death. Western blot analysis also revealed that such cell death was more likely linked to apoptosis, indicated by the bcl-2 down-regulation and the Bax up-regulation. Therefore, PE is a natural anticancer agent with prooxidant activity exerting OXS, which leads to inhibition of glycolysis, modulations of metabolic signaling pathways, and ultimately apoptosis. It may have clinical implications in oral and/or intravesical administration for a safer and better therapeutic option for bladder cancer.

surgery was approximately 7 months. Mean operative time was 173 minutes. Most patients underwent reimplant with no complication. One patient who underwent ureteral reimplant to neobladder with concomitant anterior abdominal wall hernia repair developed a fistula from the ileal-ileal anastomosis to the neobladder. This patient subsequently underwent a successful repair two weeks later with 8 day hospital stay. Mean estimated blood loss was 25 cc, and mean hospital length of stay was 2.2 days. Of note, two of these five patients had undergone prior radiation therapy for prostate cancer and had no associated complications.CONCLUSIONS: Robotic ureteral reimplant in a patient with urinary diversion is a safe and effective treatment for ureteral stricture when performed by an experienced robotic surgeon. Larger studies will be needed to demonstrate the long term safety and efficacy of this repair.

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