Hydrogen Sulfide Targets the Cys320/Cys529 Motif in Kv4.2 to Inhibit the Ito Potassium Channels in Cardiomyocytes and Regularizes Fatal Arrhythmia in Myocardial Infarction.

AIMS: The mechanisms underlying numerous biological roles of hydrogen sulfide (H2S) remain largely unknown. We have previously reported an inhibitory role of H2S in the L-type calcium channels in cardiomyocytes. This prompts us to examine the mechanisms underlying the potential regulation of H2S on the ion channels. RESULTS: H2S showed a novel inhibitory effect on Ito potassium channels, and this effect was blocked by mutation at the Cys320 and/or Cys529 residues of the Kv4.2 subunit. H2S broke the disulfide bridge between a pair of oxidized cysteine residues; however, it did not modify single cysteine residues. H2S extended action potential duration in epicardial myocytes and regularized fatal arrhythmia in a rat model of myocardial infarction. H2S treatment significantly increased survival by ∼1.4-fold in the critical 2-h time window after myocardial infarction with a protection against ventricular premature beats and fatal arrhythmia. However, H2S did not change the function of other ion channels, including IK1 and INa. INNOVATION AND CONCLUSION: H2S targets the Cys320/Cys529 motif in Kv4.2 to regulate the Ito potassium channels. H2S also shows a potent regularizing effect against fatal arrhythmia in a rat model of myocardial infarction. The study provides the first piece of evidence for the role of H2S in regulating Ito potassium channels and also the specific motif in an ion channel labile for H2S regulation.

Reliability analysis of acoustic radiation force impulse ultrasound imaging with virtual touch tissue quantification: ex vivo ox liver.

The effect of scanning angle and region of interest (ROI) depth on shear-wave velocity (SWV) was investigated in this study. Shear-wave velocity of ox liver ex vivo was measured with different approaches. Region of interest was set underneath the liver capsule at depths of 1, 2, 3, 4, and 5 cm. Three groups of measurements were performed at different scanning angles. One group of measurement was conducted with a scanning angle of 0 to 15 degrees from the midline, and the other 2 groups were performed with scanning angles of 15 to 30 degrees and 30 to 45 degrees. The data on SWV from different scan angles and ROI depths were analyzed statistically. Scanning angle and ROI depth were found to be the 2 factors that affect SWV. Interaction was observed between the scan angle and ROI depth. The data at different depths within 0- to 15-degree scanning angles exhibited no significant difference. However, the reliability of SWV decreased with the increase in ROI depth. In the groups of 15 to 30 degrees and 30 to 45 degrees, a significant difference was found between the 2 different measured depths. Scanning angle and ROI depth affected the reliability of SWV measurement. The scanning angle should be confined within 15 degrees from the midline. Therefore, SWV from shallow ROI is more reliable than that at deep ROI.

A modified single-armed technique for microsurgical vasoepididymostomy.

This study is to evaluate the effectiveness of a modified single-armed suture technique for microsurgical vasoepididymostomy (VE) in patients with epididymal obstructive azoospermia. From September 2011 to December 2011, microsurgical two-suture longitudinal intussusception VEs were performed using our modified single-armed suture technique in 17 men with epididymal obstructive azoospermia at our hospital. Two of these patients underwent repeated VEs after previous failed VEs, and one patient underwent unilateral VE because of an occlusion of the left abdominal vas deferens. The presence of sperm in the semen sample at 3 months postoperation was used as the preliminary endpoint of this study. Each patient provided at least one semen sample at the 3-month time point, and the patency was assessed by the reappearance of sperm (>10(4) ml(-1)) in the semen. The mean operative time for the modified technique was 219 min. Patency was noted in 10 men (58.8%), including one patient who underwent repeated VE. The patient who underwent unilateral anastomosis manifested no sperm postoperatively in his semen. Sperm granulomas were not detected in this cohort. The results of this study demonstrate that our modified technique for microsurgical longitudinal intussusception VE is effective. We believe that it is a practical alternative that may reduce operation time and obviate the suture crossing.

[The analysis of perioperative complications during radical cystectomy using a standardized reporting system].

OBJECTIVES: To analyze the perioperative complications of radical cystectomy using a standardized reporting methodology. METHODS: The clinical data of 233 cases of radical cystectomy from January 1996 to December 2008 were reviewed. Two hundred male patients and 33 female patients were included. The mean age was 58.9 years old. All complications within 30 days of surgery were recorded and classified using a 5-grade modification of the Clavien system. RESULTS: Overall mean operative time was 339 (170 - 610) minutes, and mean blood loss was 818 (range 100 to 3500) ml. Of the 233 subjects at least 1 postoperative complication developed in 84 (36.1%), including five cases of intraoperative complications. According to the modified Clavien system, 27 patients (11.6%) had grade 1, 38(16.3%) had grade 2, 16(6.9%) had grade 3, and 3(1.7%) had grade 4 complications. The most frequent complication was gastrointestinal complications (15.9%), then the incision-related complications (15.0%) and lung infections (4.7%). An association between hypoproteinemia and any complication was found after adjusting for confounding variables (OR = 2.963, 95%CI: 1.451 - 6.050, P = 0.003), and American society of anesthesia score (ASA score) was significantly associated with any major complication (OR = 2.520, 95%CI: 1.003 - 6.332, P = 0.049). CONCLUSIONS: Radical cystectomy is associated with a high perioperative complications, using the modification of the Clavien system has allowed us to stratify complications during radical cystectomy. Hypoproteinemia is independently associated with any complication in these patients and ASA score was significantly associated with any major complication.

[Efficacy of transurethral resection of ejaculatory duct for treatment of ejaculatory duct obstruction: report of 60 cases].

OBJECTIVE: To evaluate the effect of transurethral resection of ejaculatory duct (TURED) for treatment of ejaculatory duct obstruction (EDO). METHODS: The clinical data of 60 cases of EDO from Oct. 2004 to Oct. 2010 were analyzed. The diagnostic criteria included semen analyses, fructose in seminal plasma, transrectal ultrasonography (TRUS), and vasography if necessary. All the patients were treated by TURED. Post-operative semen assay, postoperative patency rate and postoperative impregnation rate were followed. RESULTS: Semen analyses in the majority of cases showed the typical characteristics of EDO, azoospermia, low semen volume (average 1.10 ± 0.76 mL), low pH (average 6.5 ± 1.4), absent or low semen fructose (average 5.86 ± 2.19 µmol/one ejaculation). TRUS showed pure dilation of both ejaculatory ducts in 15 cases, prostatic cyst in 6, pure dilated seminal vesicles on both sides in 10, unilateral dilated seminal vesicle in 4, dilation of both ejaculatory duct and seminal vesicles in 10, dilated seminal vesicles with prostatic cyst in 5, unilateral dilated seminal vesicle and contralateral aplasia of seminal vesicle in 2, dilated seminal vesicles with dilation and calcifications of both ejaculatory ducts in 3. The remaining 5 had unilateral dilated ejaculatory duct and seminal vesicle with contralateral aplasia of seminal vesicle. In all the cases followed up more than 6 to 78 months after TURED, 51 patients (85.0%) had improved semen parameters and 16 patients' wives (26.7%) had pregnancies. CONCLUSION: TURED may be the simple, minimally invasive and effective method for the treatment of EDO.

Comparison of hand-assisted laparoscopic and open radical cystectomy for bladder cancer.

PURPOSE: To present our experience of hand-assisted laparoscopic radical cystectomy (HALRC) and compare it with open radical cystectomy (ORC). PATIENTS AND METHODS: During the period between May 2004 and November 2007, 31 patients underwent HALRC and 39 patients underwent ORC for bladder cancer. The patient demographics, intraoperative variables and postoperative outcomes were compared retrospectively. RESULTS: There was no statistically significant difference with regard to age, sex, body mass index, and urinary diversion in the 2 groups. In the HALRC group, 20 patients had stage pT2 or less, 7 had pT3 disease, and 4 had stage pT4 disease. In the ORC group, 29 patients had stage pT2 or less, 5 had pT3 disease, and 5 had stage pT4 disease. All margins in both groups were negative. The HALRC group had decreased blood loss (250.9 vs. 812.8 ml, p < 0.001) and a lower rate of transfusion (9.7 vs. 76.9%, p < 0.001), but similar mean operative time (365.7 vs. 362.6 min, p = 0.862). Time to liquid diet was significantly less in the HALRC group versus the ORC group (4.3 vs. 6.3 days, p < 0.001). The median number of lymph nodes were similar between the HALRC and ORC groups (14 vs. 15, p = 0.377). Six patients developed perioperative complications in the HALRC group and 12 patients had complications in the ORC group (19.4 vs. 30.8%, p = 0.278). Late complications occurred in 3 patients (2 parastomal hernias and 1 ureteroenteral stricture) in the HALRC group. CONCLUSIONS: Compared with ORC, HALRC patients had decreased blood loss, less transfusion requirements, and quicker intestinal recovery. Long-term follow-up in a larger cohort of patients is needed to assess the long-term oncological and functional outcomes.

Long-term sexual activity status and influencing factors in men after surgery for hypospadias.

The aim of this study was to compare the long-term postoperative status of hypospadiac patients by analysing their sexual psychology, sexual behaviour, sexual function and influencing factors. A total of 130 hypospadiac patients hospitalized between January 1988 and December 2007 were followed up with questionnaires using Zung's Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), a self-designed sexual function questionnaire and a 5-item version of the International Index of Erectile Function (IIEF-5). The surveys served to evaluate the effects of hypospadias type, number of operations and surgical procedures on sexual psychology, sexual behaviour and sexual function. The control group consisted of 50 healthy adults. The postoperative SDS / SAS scores and occurrences of depression/anxiety in hypospadiac patients were significantly higher than those of normal controls (P < 0.001). Patients with proximal hypospadias and multiple procedures differed from those with distal hypospadias and a single procedure in all parameters of sexual psychology (P < 0.05). The average penile lengths and circumferences of hypospadiac patients under either erect or flaccid conditions were significantly shorter than those of normal controls (P < 0.001). A similar difference existed between patients with distal and proximal hypospadias (P < 0.01). There was no significant difference in any parameter of sexual function between patients with different numbers of operations and surgical procedures. Hypospadiac patients were clearly impaired in sexual psychology and penile development. The severity of hypospadias and number of operations were key factors that influenced the sexual psychology of patients. This finding indicated the importance of long-term follow-up and psychological counselling for hypospadiac patients postoperatively.

[Effects of alprostadil and ulinastatin on inflammatory response and lung injury after cardiopulmonary bypass in pediatric patients with congenital heart diseases].

OBJECTIVE: To investigate the therapeutic effects of alprostadil (Lipo-PGE1) and Ulinastatin on inflammatory response and lung injury after cardiopulmonary bypass (CPB) in pediatric patients with congenital heart diseases. METHODS: 58 children with congenital heart diseases, including atrial septal defect, ventricular septal defect, and atrioventricular septal defect, scheduled to undergo CPB, aged 4 - 72 months, were randomly divided into 4 groups: alprostadil Group P (n = 15) receiving alprostadil 10 ng/ml added into the prime solution and continuous pump infusion of alprostadil 10 ngxkg(-1)xmin(-1) via central vein until the end of operation, Group U (n = 15) receiving ulinastatin 20 000 U/kg divided into several doses to be added into the prime solution, Group PU (n = 14) receiving alprostadil and ulinastatin according to the above protocols, and Group C (control group, n = 14) receiving normal saline of the equal volume. Electrocardiogram (ECG), heart rate (HR), pulse oxygen saturation (SpO(2)), and mean arterial pressure (MAP) were continuously monitored during operation. Duration of mechanical ventilation and staying in ICU were also recorded. Plasma neutrophil (PMN), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha and matrix metalloproteinase (MMP-9) levels in the radial arterial blood samples were measured after induction of anesthesia before CPB (T(1)), 30 minutes and (T(2)), 2 hours (T(3)), 6 hours (T(4)), and 24 hours (T(5)) after the declamping of aorta. Inhaled oxygen concentration and arterial blood gas analysis were recorded at T(1), T(2), and T(3) for calculation of oxygenation index (OI). RESULTS: There were no significant differences in the MAP and HR among these four groups at any time points (all P > 0.05). The umbers of PMN and the levels of IL-6, IL-8, and TNF-alpha at T(2) and T(3) of Groups P, U, and PU were all significantly lower than that of Group C (all P < 0.05), with those of Group PU being the lowest. The IL-10 levels at T(2) and T(3) of Groups U and PU were significantly higher than that of Group C (both P < 0.05), the level of MMP-9 at T(2) and T(3) of Groups U and PU were significantly lower than that of Group C (all P < 0.05), however, there was not significant difference between Group P and Group C (P > 0.05). The OIs at T(2) of Groups P, U, and PU were significantly higher than that of Group C (all P < 0.05). The mechanical ventilation time of Groups P, U, and PU were all significantly shorter than that of Group C, and that of Group PU was significantly shorter than that of group C (P < 0.05). CONCLUSION: Decreasing the inflammatory response after CPB, alprostadil and ulinastatin used during CPB effectively reduce the pulmonary injury via inhibition of the neutrophil activation and cytokines release.

Hydrogen sulphide is an inhibitor of L-type calcium channels and mechanical contraction in rat cardiomyocytes.

AIMS: Hydrogen sulphide (H(2)S) is an endogenously generated gaseous transmitter that has recently been suggested to regulate cardiovascular functions. To date, there is no direct evidence for a potential role of H(2)S in regulating calcium channels in the heart. The present study aims to examine the hypothesis that H(2)S is a novel inhibitor of the L-type calcium channel current (I(Ca,L)). METHODS AND RESULTS: Electrophysiological measurements were performed in cardiomyocytes isolated from Wistar-Kyoto and spontaneously hypertensive rats. Bath application of 100 microM NaHS (a H(2)S donor) significantly reduced the time required for the repolarization of the action potential. Inhibition of the peak I(Ca,L) by NaHS was determined to be concentration-dependent (25, 50, 100, 200, and 400 microM). NaHS inhibited the recovery from depolarization-induced inactivation. Electric field-induced [Ca(2+)]i transients and contraction of single cardiomyocytes and isolated papillary muscles were reduced by NaHS treatment. In contrast, caffeine induced an increase in [Ca(2+)]i that was not altered by NaHS. NaHS had no effect on the K(ATP) current or on the levels of cAMP and cGMP in the current study. CONCLUSION: H(2)S is a novel inhibitor of L-type calcium channels in cardiomyocytes. Moreover, H(2)S-induced inhibition of [Ca(2+)]i appears to be a secondary effect owing to its initial action towards I(Ca,L). The inhibitory effect of H(2)S on I(Ca,L) requires further investigation, particularly in the exploration of new pathways involved in cardiac calcium homeostasis and disease pathology.