Safety and Efficacy of Intravesical Epinephrine Instillation in Patients with Intractable Lower Urinary Tract Hematuria - A Novel Approach.

OBJECTIVE: To treat intractable hematuria with intravesical instillation of epinephrine. METHODS: Sixty patients were treated with intravesical instillation of epinephrine at Mackay Memorial Hospital. The control group was composed of 60 patients who were treated with standard-of-care cystoscopic electrocautery fulguration. Under general anesthesia, epinephrine-treated group were injected with 150 mL of diluted epinephrine (1:10,000) through cystoscopy, followed by bladder irrigation with 1:100,000-diluted epinephrine at the ward. Successful hemostasis was defined as hematuria resolution within 1 month post-treatment without additional invasive procedures. RESULTS: In the 60 patients who underwent intravesical instillation of epinephrine, radiation cystitis was the most common etiology (65.0%). Fifty-two patients (86.7%) required no additional therapy within 1 month after one course of intravesical epinephrine instillation treatment compared with 28 patients (46.7%) in the electrocautery fulguration-control group (P <.001). We observed a significant decrease in both the median length of hospitalization (P = .049) and the need for additional invasive procedures (P <.001) in the epinephrine group. In addition, cardiopulmonary monitoring of mean blood pressure, mean heart rate, and mean respiratory rate demonstrated no significant differences after epinephrine treatment. CONCLUSION: In this study, intravesical instillation of epinephrine was an innovative method of hemostasis for intractable lower urinary tract hematuria with a success rate of 86.7%, compared to 46.7% in the control group, and significantly reduced the number of additional procedures required and the length of hospitalization. It was well-tolerated by all patients, and was a safe and effective treatment modality for intractable hematuria or bladder hemorrhage.

Analysis of risk factors of bladder neck contracture following transurethral surgery of prostate.

BACKGROUNDS: The aim of the present study was to investigate the perioperative parameters associated with bladder neck contracture (BNC) after transurethral surgery of the prostate and to compare the incidence of BNC after transurethral resection of the prostate (TURP) or Thulium vaporesection (resection group) versus Thulium vapoenucleation or enucleation of the prostate (enucleation group). METHODS: Between March 2008 and March 2020, 2363 patients received TURP and 1656 patients received transurethral surgery of the prostate with Thulium laser (ThuP) at Mackay Memorial Hospital. A total of 62 patients developed BNC. These BNC patients were age-and operation-matched to 124 randomly sampled TURP/ThuP controls without BNC. A 1:1 propensity score matching model was used to evaluate the difference in incidence of BNC. RESULTS: Our study demonstrated that a greater proportion of BNC patients had history of cerebrovascular accidents (11/62 vs. 7/124, p = 0.009), coronary artery disease (14/48 vs. 16/108, p = 0.03), chronic kidney disease (14/62 vs. 11/124, p = 0.01), and two or more comorbidities (29/62 vs. 27/124, p = 0.001) compared with NBNC patients. Multivariate analysis showed that smaller prostate volume (OR 0.96 (0.94-0.99), p = 0.008) and recatherization (OR 5.6 (1.02-30.6), p = 0.047) were significantly associated with BNC. A ROC curve predicted that a prostate volume < 42.9 cm3 was associated with a notably higher rate of BNC. The propensity score matching model reported there was no difference in incidence between resection and enucleation groups. CONCLUSION: This study demonstrated that incidence of BNC was the same in different surgical techniques and that low prostate volume, recatherization and ≥ 2 comorbidities were positively correlated with the development of BNC after TURP or ThuP.

The relationship between androgen deprivation therapy and depression symptoms in patients with prostate cancer.

AIM: In this study, we administered a questionnaire to consecutive prostate cancer patients who received androgen deprivation therapy (ADT) for understanding the prevalence of depression symptoms. MATERIALS AND METHODS: We retrospectively identified patients with prostate adenocarcinoma who received ADT between January 2015 and February 2018 at Mackay Memorial Hospital. The patients were then asked to complete the Chinese version of the Patient Health Questionnaire-9 (PHQ-9) during an interview. The patients were divided into two groups according to PHQ-9 score: those with depression symptoms (PHQ-9 ≥ 6, depression group), and those without depression symptoms (PHQ-9 < 6, non-depression group). Two groups were compared using t-tests and correlation coefficients, as appropriate. Statistical significance was set at p < .05. RESULTS: There were no significant correlations between PHQ-9 scores and any of the parameters in the patients overall. In subgroup analysis, a positive correlation was found between the duration of ADT and PHQ-9 score in the patients with depression symptoms (p = .03). In addition, univariate analysis showed a positive association between the duration of ADT and PHQ-9 score, and a longer duration of ADT was further independently associated with increased PHQ-9 score in multivariate analysis in the patients with depression symptoms. CONCLUSION: This study demonstrated that in patients with prostate cancer and depression symptoms, the severity of the depression symptoms was positively correlated with the duration of ADT. In contrast, this association was not found in patients without depression symptoms.

Comparison of electrohydraulic and electromagnetic extracorporeal shock wave lithotriptors for upper urinary tract stones in a single center.

PURPOSE: To compare the efficacy and outcomes of shock wave lithotripsy (SWL) for upper urinary tract stones with an electrohydraulic (EH) and an electromagnetic (EM) lithotriptor in a single center. METHODS: The medical records of 272 patients with upper urinary tract stones ≤ 2 cm in size who underwent SWL with either the Medispec E3000 EH lithotriptor (179 cases) or the Medispec EM1000 EM lithotriptor (93 cases) were reviewed. The demographic data, stone parameters, stone-free rates, and retreatment rates were analyzed. RESULTS: The EH group had a higher stone-free rate (53.6 vs. 30.1%, p < 0.001) and a lower retreatment rate (32.4 vs. 61.2%, p < 0.001) for renal and upper third ureteral stones than the EM group. The stone-free rates for renal stones < 1 cm (55.5 vs. 32.2%, p = 0.045), ureteral stones < 1 cm (64.5 vs. 42.1%, p = 0.028), and renal stones ≥ 1 cm (43.1 vs. 0%, p = 0.03) were higher in the EH group. Two patients in the EH group had a renal hematoma needing hospitalization after SWL. There were no complications in the EM group. CONCLUSIONS: The Medispec E3000 EH lithotriptor had higher stone-free rates and lower retreatment rates than the Medispec EM1000 EM lithotriptor for renal stones < 2 cm and ureteral stones < 1 cm. Complications were rare.

Combination of Thulium Laser Incision and Bipolar Resection Offers Higher Resection Velocity than Bipolar Resection Alone in Large Prostates.

PURPOSE: We compared the efficacy and safety of a combined thulium laser incision and bipolar resection of prostate technique (web procedure) with traditional bipolar TURP. MATERIALS AND METHODS: We reviewed the medical records of 96 web procedure, 93 traditional bipolar TURP patients between 2013 and 2016. The web procedure consisted of thulium laser incision of the prostate at 3, 5, 7, 9 and 12 o'clock positions up to the resection plane and subsequent bipolar resection of the created prostate blocks.  Resected tissue weight, operative time, resection velocity, complications, blood loss, and early operative outcome were compared. RESULTS: No significant differences were noted among the web procedure (web group) and traditional bipolar TURP in preoperative PSA ( 6.3 vs 8.7 ng/mL, P =0.295), preoperative postvoid residual urine (55.1 vs 76.4, P =.056), modified hemoglobin decrease (defined as total Hb decrease divided by the weight of the resected tissue: 0.060 vs 0.051, p=.380), complication rate (5.2% vs 5.3 %, P =.958), hospitalization (4.0 vs 4.2 days, P =.120) and catheterization (2.5 vs 3.4, p=.066). The resection velocity was higher in the web group (0.23 vs 0.17 g/ min, p=.001). In subgroup analysis, the significant difference of resection velocity between two group was showed in large prostates (>40 g: 0.25 vs 0.20 g/min, P =0.02 ) but not in the small prostate group. There was no difference in postoperative postvoid residual urine (21.9 vs 30.3 P =.231) and postvoid residual urine decrease (33.1 vs 45.5, P = .167) 2 months after surgery. CONCLUSION: The combination thulium laser incision and bipolar TURP technique had a higher resection efficiency and comparable efficacy and safety than traditional bipolar TURP.

Zerumbone Regulates DNA Repair Responding to Ionizing Radiation and Enhances Radiosensitivity of Human Prostatic Cancer Cells.

INTRODUCTION: Radiation therapy using ionizing radiation is widely used for the treatment of prostate cancer. The intrinsic radiation sensitivity of cancer cells could be enhanced by modulating multiple factors including the capacity to repair DNA damage, especially double-strand breaks (DSBs). We aimed to examine the effect of zerumbone on radiation sensitivity and its protective effects against ionizing radiation-induced DSB in human prostate cancer cells. MATERIALS AND METHODS: The human prostate cancer PC3 and DU145 cell lines were used. A colony formation assay was performed to analyze the radiation survival of cells. DNA histogram and generation of reactive oxygen species (ROS) were examined using flow cytometry. Western blotting was used to examine the expression of regulatory molecules related to DNA damage repair. RESULTS: Pretreatment with zerumbone enhanced the radiation effect on prostate cancer cells. Zerumbone delayed the abrogation of radiation-induced expression of γ-H2AX, an indicator of DNA DSB. Zerumbone pretreatment markedly reduced ionizing radiation-induced upregulated expression of phosphorylated ATM (ataxia telangiectasia-mutated), which was partially reversed by the ATM agonist methyl methanesulfonate. Ionizing radiation augmented and zerumbone pretreatment reduced the expression of Jak2 and Stat3, which are involved in DNA damage repair signaling. No significant effect on the generation of ROS and expression of ATR was noted after zerumbone treatment. CONCLUSION: Zerumbone sensitized DU145 and PC3 prostatic cancer cells to ionizing radiation by modulating radiation-induced ATM activation during repair of DNA DSBs.

Comparison of safety and outcomes of shock wave lithotripsy between elderly and non-elderly patients.

BACKGROUND: This study compared the clinical outcomes of extracorporeal shock wave lithotripsy between elderly (aged $65 years) and non-elderly (aged <65 years) patients. METHODS: A retrospective review of medical records was performed on 483 (non-elderly: 245, elderly: 238) patients with upper urinary tract stones who underwent shock wave lithotripsy between 2007 and 2015. The demographic data, stone parameters, stone-free rate, retreatment rate, and complication rate were analyzed in both elderly and non-elderly patient groups. RESULTS: There was no significant difference between non-elderly and elderly patients in terms of stone-free rate (46.5% vs 41.1%, P>0.05) regardless of stone site or stone size and overall retreatment rate (41.6% vs 37.0%, P>0.05). Elderly patients had a higher complication rate than non-elderly patients (15.5% vs 23.5%, P=0.026). The most common complication was flank pain. Receiver operating characteristic curves predicted that elderly patients (cutoff value: 65 years of age) had a higher risk of complications and that patients with smaller stones (cutoff value: 0.8 cm) had a higher stone-free rate. CONCLUSION: This study showed that elderly patients with upper urinary tract stones undergoing shock wave lithotripsy had comparable efficacy for stone-free rates and retreatment rates, but higher complication rates.

Concomitant transrectal ultrasound-guided biopsy and transurethral resection of prostate in patients with urinary retention and elevated serum prostate-specific antigen levels.

BACKGROUND: There was no consensus about the management of patients with urinary retention and elevated serum prostate-specific antigen (PSA) levels. This study aimed to determine whether concomitant transrectal ultrasound (TRUS)-guided biopsy and transurethral resection of prostate (TURP) is practical in patients with urinary retention and elevated serum PSA levels. METHODS: From March 2007 to May 2015, a total of 34 patients with urinary retention and elevated PSA (≥ 4 ng/mL) underwent concomitant TRUS-guided biopsy and TURP. The medical records were evaluated retrospectively, and data including PSA, prostate volume, TURP results, TRUS-guided biopsy results, length of hospitalization, and complications were collected. These patients were then compared with 40 patients with urinary retention who underwent TURP alone. RESULTS: The mean age of the patients was 71.6 years. The mean PSA levels were 16.9 ng/mL. Prostate cancer was detected in eight cases (23.5%): one case by TRUS-guided biopsy alone, two cases by TURP alone, and five cases by both TRUS-guided biopsy and TURP. Complications included fever in five patients (14.7%), recatheterization for urine retention in two patients (5.9%), urinary tract infection in two patients (5.9%), and de novo urge incontinence in seven patients (20.6%). The complication rate was not significantly increased compared with that of the patients who underwent TURP alone. CONCLUSION: This study showed that concomitant TRUS-guided biopsy and TURP was safe and of possible clinical significance in urinary retention patients with elevated serum PSA.

FTY720 inhibits germ cell apoptosis in testicular torsion/detorsion.

BACKGROUND: Testicular torsion/detorsion (T/D) can induce germ cells apoptosis, which may lead to impairment of spermatogenesis. FTY720, an agonist of the sphingosine-1-phosphate receptor 1 (S1PR1), inhibits apoptosis in ischemic stroke. We examined whether FTY720 could mitigate germ cell apoptosis in testicular T/D rats. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were allocated to receive testicular T/D (the T/D group), T/D plus FTY720 (the T/D-FTY group), or T/D plus FTY720 plus the potent S1PR1 antagonist VPC23019 (the T/D-FTY-VPC group; n = 6 in each group). Sham control groups were run simultaneously. At 24 h after detorsion, rats were euthanized. RESULTS: Our data revealed that, in the ipsilateral twisted testes, sperm counts and expression of the S1PR1 of the T/D and the T/D-FTY-VPC groups were significantly lower than those of the T/D-FTY group (all P < 0.001). In contrast, signals of apoptotic cells stained by terminal deoxynucleotidyl transferase dUTP nick end labeling and the proapoptotic protein cleaved caspase-3 of the T/D, and the T/D-FTY-VPC groups were significantly stronger than those of the T/D-FTY group. Moreover, the terminal deoxynucleotidyl transferase dUTP nick end labeling signals mainly localized to germ cells. CONCLUSIONS: FTY720 could mitigate testicular T/D-induced germ cell apoptosis, and the mechanisms may involve the S1PR1.

FTY720 mitigates torsion/detorsion-induced testicular injury in rats.

BACKGROUND: FTY720, a sphingosine-1-phosphate (S1P) receptor agonist, possesses potent anti-inflammation capacity. We evaluated the therapeutic potentials of FTY720 against testicular injury induced by testicular torsion and/or detorsion (T/D). MATERIALS AND METHODS: Young adult male Sprague-Dawley rats were allocated to receive T/D (the T/D group) and T/D plus FTY720 (4 mg/kg, the T/D-FTY group, n = 6 in each group). To investigate the possible roles of the S1P receptors, another group of rats received T/D plus FTY720 plus the potent S1P receptor antagonist VPC23019 (1 mg/kg, the T/D-FTY-VPC group, n = 6). FTY720 was administered immediately before testicular detorsion, and VPC23019 was administered 30 min before FTY720. Another set of rats that received sham operation, immediately followed by injection of normal saline, FTY720, or FTY720 plus VPC23019, served as control groups. Sham control groups were run simultaneously. After euthanization, levels of testicular injury were measured. RESULTS: Histologic findings revealed severe testicular injury changes in both the T/D and T/D-FTY-VPC groups and moderate testicular injury changes in the T/D-FTY group. In addition, malondialdehyde activity (oxidative status), concentration of interleukin-1ß (inflammation index), myeloperoxidase activity (neutrophil infiltration index), and wet-to-dry weight ratio (tissue edema index) of both the T/D and T/D-FTY-VPC groups were significantly higher than those of the T/D-FTY group. These data confirmed the protective effects of FTY720 against testicular T/D. Moreover, antagonizing the S1P receptors could reverse the protective effects of FTY720. CONCLUSIONS: FTY720 significantly mitigated testicular injury induced by testicular T/D. The mechanisms may involve activating the S1P receptors.

Identification and characterization of repopulating spermatogonial stem cells from the adult human testis.

BACKGROUND: This study was conducted to identify and characterize repopulating spermatogonial stem cells (SSCs) in the adult human testes. METHODS: Testes biopsies from obstructive azoospermic patients and normal segments of human testicular tissue were used. Flow cytometry, real-time PCR and immunohistochemical analysis were performed. Purified human spermatogonia were transplanted into busulfan-treated recipient mouse testes and integrated cells were detected by human nuclear protein antibody co-localized with stem cell and germ cell markers. RESULTS: Testicular biopsies collected from obstructive azoospermic men showed similar morphology and distribution of markers to the normal human testes. Flow cytometry showed distinct populations of stage-specific embryonic antigen-4 (SSEA-4), CD49f and CD90 positive cells in the adult human testes. SSEA-4 (+) cells showed high expression levels of SSC-specific genes and high levels of telomerase activity. Extensive colonization of human cells in the mouse testes indicates the presence of highly enriched populations of SSCs in the SSEA-4 (+) sorted cells. All the HNP (+) cells in the mouse testes were positive for germ cell marker dead box mRNA helicase and only half of them were dimly positive for c-kit. In addition, subpopulations of human spermatogonia that colonized mouse testes were positively stained for CD49f, GPR-125, Nanog and Oct-4 indicating the existence of population of cells among human spermatogonia with SSC and pluripotent characteristics. CONCLUSIONS: This study clearly demonstrates that repopulating human SSCs have phenotypic characteristics of SSEA-4(+), CD49f(+), GPR-125(+)and c-Kit (neg/low). The results have direct implications for enrichment of human spermatogonia for further culture and germ cell differentiation studies.

Simvastatin attenuates testicular injury induced by torsion-detorsion.

PURPOSE: The lipid lowering agent simvastatin has potent anti-oxidation capacity. We elucidated the potential of simvastatin to attenuate testicular injury induced by testicular torsion-detorsion. We also investigated simvastatin effects on nuclear factor-kappaB expression. MATERIALS AND METHODS: We allocated 60 adult male Sprague-Dawley(R) rats to testicular torsion-detorsion, torsion-detorsion plus simvastatin (1 or 5 mg/kg), sham operation or sham operation plus simvastatin (5 mg/kg). There were 12 rats per group. Simvastatin was administered immediately after detorsion or immediately after sham operation. Testes were harvested 30 minutes and 24 hours after detorsion to facilitate the evaluation of nuclear factor-kappaB and testicular injury, respectively. RESULTS: Histological findings revealed severe injury in testes of the torsion-detorsion and torsion-detorsion-simvastatin (1 mg/kg) groups while testes in the torsion-detorsion-simvastatin (5 mg/kg) group showed moderate injury. Myeloperoxidase activity, and cytokines, nitric oxide and malondialdehyde in testes in the torsion-detorsion-simvastatin (5 mg/kg) group were significantly lower than in the torsion-detorsion group. Values were comparable in the torsion-detorsion-simvastatin (1 mg/kg) and torsion-detorsion groups. Testicular concentrations of nuclear factor-kappaB in nuclear extracts and phosphorylated inhibitor-kappaB in cytosolic extracts in the torsion-detorsion-simvastatin (5 mg/kg) group were significantly lower than in the torsion-detorsion group. Values were comparable in the torsion-detorsion-simvastatin (1 mg/kg) and torsion-detorsion groups. CONCLUSIONS: Simvastatin protected testes from torsion-detorsion injury in a dose dependent manner. Mechanisms may involve attenuating nuclear factor-kappaB activation and decreasing oxidative stress induced by torsion-detorsion.

Differentiation potential of germ line stem cells derived from the postnatal mouse ovary.

General belief in reproductive biology is that in most mammals female germ line stem cells are differentiated to primary oocytes during fetal development and oogenesis starts from a pool of primordial follicles after birth. This idea has been challenged previously by using follicle kinetics studies and demonstration of mitotically active germ cells in the postnatal mouse ovary (Johnson et al., 2004; Kerr et al., 2006; Zhang et al., 2008). However, the existence of a population of self-renewing ovarian germ line stem cells in postnatal mammals is still controversial (Eggan et al., 2006; Telfer et al., 2005; Gosden, 2004). Recently, production of offspring from a germ line stem cell line derived from the neonatal mouse ovary was reported (Zou et al., 2009). This report strongly supports the existence of germ line stem cells and their ability to expand in vitro. Recently, using a transgenic mouse model in which GFP is expressed under a germ cell-specific Oct-4 promoter, we isolated and generated multipotent cell lines from male germ line stem cells (Izadyar et al., 2008). Using the same strategy we isolated and derived cell lines from postnatal mouse ovary. Interestingly, ovarian germ line stem cells expanded in the same culture conditions as the male suggesting that they have similar requirements for their self-renewal. After 1 year of culture and many passages, ovarian germ line stem cells maintained their characteristics and telomerase activity, expressed germ cell and stem cell markers and revealed normal karyotype. As standard protocol for differentiation induction, these cells were aggregated and their ability to form embryoid bodies (EBs) was investigated. EBs generated in the presence of growth factors showed classical morphology and expressed specific markers for three germ layers. However, in the absence of growth promoting factors EBs were smaller and large cells with the morphological and molecular characteristics of oocytes were formed. This study shows the existence of a population of germ line stem cell in postnatal mouse ovary with multipotent characteristics.

Catheter-assisted transurethral resection of the prostate: a novel approach.

INTRODUCTION: The aim of the study was to compare the safety and efficacy of catheter-assisted transurethral resection of the prostate (TURP) with traditional TURP in the treatment of benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 61 men were randomized to either catheter-assisted TURP (30 patients) or traditional TURP (31), both performed with a monopolar device. Measurements included the duration of Foley catheterization, length of hospital stay, symptom score and urinary flow rate. All patients were followed for at least 1 year after surgery. RESULTS: The catheter-assisted group had a significantly shorter operative time, duration of postoperative catheterization and length of stay. There were no significant differences in changes in serum sodium and hemoglobin level on postoperative day 1. At 1 year postoperatively, none of the patients suffered from urethral stricture and the 2 groups did not differ significantly in terms of prostatic volume, peak flow rate or International Prostate Symptom Score. CONCLUSIONS: Catheter-assisted TURP is safe and produced results at 1 year similar to traditional TURP. This new method for TURP appears to be a better and more effective approach than the traditional method, although a longer period of observation is needed to assess the durability of the results.

Hemin induced heme oxygenase-1 over expression involves nuclear factor-E2 related factor-2, nuclear factor-kappaB and extracellular regulated kinase: an experimental study in a testicular torsion-detorsion rodent model.

PURPOSE: Nrf2 (nuclear factor-E2 related factor-2), nuclear factor-kappaB and mitogen-activated protein kinase, including extracellular regulated kinase, c-jun N-terminal kinase and p38 mitogen-activated protein kinase, are crucial for signal transduction. We previously reported that heme oxygenase-1 over expression induced by the heme oxygenase-1 inducer hemin protected testes from torsion-detorsion injury. In this study we elucidated which of these enzymes is involved in hemin induced heme oxygenase-1 over expression in testicular tissues after torsion-detorsion injury. MATERIALS AND METHODS: Adult male Sprague-Dawley rats (National Science Council, Taipei, Taiwan, Republic of China) were allocated to undergo testicular torsion-detorsion immediately followed by injection of normal saline, hemin or hemin plus tin protoporphyrin, a heme oxygenase-1 inhibitor. Another set of rats that underwent sham operation were used as controls. Testes were harvested 0 and 30 minutes after detorsion and enzyme expression was analyzed. RESULTS: Hemin alone caused no significant effects on the expression of Nrf2, nuclear factor-kappaB, extracellular regulated kinase and c-jun N-terminal kinase. Similarly testicular torsion-detorsion injury caused no significant effects on Nrf2 expression. In the presence of torsion-detorsion injury hemin significantly up-regulated Nrf2 expression. Moreover, this effect was not affected by tin protoporphyrin. Unlike Nrf2, the expression of nuclear factor-kappaB, extracellular regulated kinase and c-jun N-terminal kinase was significantly up-regulated by testicular torsion-detorsion. Hemin significantly attenuated the testicular torsion-detorsion induced up-regulation of nuclear factor-kappaB and extracellular regulated kinase but not c-jun N-terminal kinase. The effects of hemin on nuclear factor-kappaB and extracellular regulated kinase were significantly reversed by tin protoporphyrin. However, the expression of p38 mitogen-activated protein kinase in rodent testes was not affected by these interventions. CONCLUSIONS: Hemin induced heme oxygenase-1 over expression in rodent testes after torsion-detorsion injury involves Nrf2, nuclear factor-kappaB and extracellular regulated kinase.

The protective role of heme oxygenase-1 induction on testicular tissues after testicular torsion and detorsion.

PURPOSE: Testicular torsion-detorsion has been identified as an ischemia-reperfusion type of injury. We elucidated the protective role of heme oxygenase-1 super induction on testicular torsion-detorsion injury. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were randomly allocated to undergo testicular torsion-detorsion, immediately followed by injection of normal saline, the heme oxygenase-1 inducer hemin or hemin plus the heme oxygenase-1 inhibitor tin protoporphyrin. Another set of rats that underwent sham operation, immediately followed by injection of normal saline, hemin or hemin plus tin protoporphyrin, served as controls. Testes were harvested 4 and 24 hours after detorsion, respectively, in the experimental groups or at comparable time points in the control groups. RESULTS: Histological evaluation confirmed that torsion-detorsion caused significant testicular tissue injury. Torsion-detorsion also caused significant increases in the testicular levels of nitric oxide, malondialdehyde, myeloperoxidase activity and heme oxygenase-1. The heme oxygenase-1 inducer hemin significantly enhanced the heme oxygenase-1 expression induced by torsion-detorsion and in turn attenuated testicular injury, and increases in nitric oxide, malondialdehyde and myeloperoxidase activity. In addition, the protective effects of hemin were significantly offset by the heme oxygenase-1 inhibitor tin protoporphyrin. CONCLUSIONS: Super induction of heme oxygenase-1 protects testes from torsion-detorsion injury.

Prophylactic intravesical instillation of epinephrine prevents cyclophosphamide-induced hemorrhagic cystitis in rats.

The objective of this study is to investigate the potential protective effects of intravesical instillation of epinephrine in cyclophosphamide-induced hemorrhagic cystitis. In an earlier study, we have shown that epinephrine promotes hemostasis on established hemorrhagic cystitis induced by cyclophosphamide. Female Sprague-Dawley rats were divided into seven groups as follows: group 1: positive control (150 mg/kg, cyclophosphamide, i.p.), group 2: negative control (10 microg/ml, epinephrine, intravesical), co-administration of cyclophosphamide (150 mg/kg, i.p.), group 3: saline (intravesical), groups 4-6: epinephrine (2.5, 5, and 10 mu g/ml, intravesical), and group 7: mesna (50 mg/kg, i.p.). Rats were sacrificed on 3 consecutive days and the urinary bladders were removed, weighed, and evaluated. The vesical vascular permeability was determined by wet bladder weight and Evan's blue dye absorbance. After 24 hours of cyclophosphamide administration, severe hemorrhagic cystitis was induced with marked edema, hemorrhage, and inflammation. In the epinephrine-treated groups, symptoms of hemorrhagic cystitis (such as edema, inflammation, and hemorrhage) were reduced significantly. Intravesical instillation of epinephrine prevents edema, hemorrhage, and inflammation in rats with cyclophosphamide-induced hemorrhagic cystitis.

Epinephrine promotes hemostasis in rats with cyclophosphamide-induced hemorrhagic cystitis.

OBJECTIVES: To evaluate the hypothesis that intravesical instillation of epinephrine would attenuate bladder hemorrhage in a rat model of cyclophosphamide (CYP)-induced hemorrhagic cystitis. METHODS: Female Sprague-Dawley rats were divided into seven treatment groups: positive control (CYP, 150 mg/kg), negative control (epinephrine, 10 microg/mL), intravesical instillation of normal saline (vehicle) and epinephrine (2.5, 5, and 10 microg/mL), and intraperitoneal administration of mesna (50 mg/kg). Rats were killed on days 1, 2, and 3, and the urinary bladders were removed, weighed, and evaluated by gross and histologic analysis. Vesical vascular permeability was determined by wet bladder weight and Evan's blue dye absorbance. RESULTS: Cyclophosphamide administration induced severe hemorrhagic cystitis with marked edema, hemorrhage, and inflammation. All three epinephrine-treated groups had marked attenuation of hemorrhagic cystitis compared with the positive and negative control and mesna-treated groups. Epinephrine was also associated with significant inhibition of tissue edema, indicating decreased vesical vascular permeability. CONCLUSIONS: In this rat model of CYP-induced hemorrhagic cystitis, intravesical instillation of epinephrine inhibited edema, hemorrhage, and inflammation.

Mechanisms of digoxin and digitoxin on the production of corticosterone in zona fasciculata-reticularis cells of ovariectomized rats.

Previous studies have indicated that digoxin (DG) inhibits testosterone production by rat testicular interstitial cells through both in vivo and in vitro experiments. DG and digitoxin (DT), but not ouabain, inhibit the progesterone, pregnenolone, and corticosterone secretion by rat granulosa cells, luteal cells, and zona fasciculata-reticularis (ZFR) cells, respectively. However, the effect of DG and DT on the enzyme kinetics of cytochrome P450 side chain cleavage enzyme (P450scc), the protein expression of P450scc and steroidogenic acute regulatory protein (StAR), and mRNA expression of StAR are unclear. ZFR cells were prepared from adrenocortical tissues of ovariectomized rats, and then challenged with adrenocorticotropin (ACTH), 8-Br-cAMP, forskolin, A23187, cyclopiazonic acid (CPA), nicotinic acid adenine dinucleotide phosphate (NAADP), trilostane, 25-OH-Cholesterol, progesterone, or deoxycorticosterone in the presence of DG, DT, or ouabain for 1 h. Enzyme kinetics of P450scc, protein expression of acute regulatory protein (StAR) and P450scc, and mRNA expression of StAR were investigated. DG and DT but not ouabain suppressed basal and other evoked-corticosterone release significantly. DG and DT also inhibited pregnenolone production. The Vmax of the DG and DT group was the same as the control group, but the Km was higher in DG- and DT-treated group than in control group. DT and ouabain significant suppressed mRNA expression of StAR. DG and DT had no effect on the P450scc and StAR protein expression at basal state, but diminished ACTH-induced StAR protein expression to basal level. These results indicated that DG and DT have an inhibitory effect on corticosterone production via a Na+, K+-ATPase-independent mechanism by diminishing actions on cAMP-, Ca2+-pathway, competitive inhibition of P450scc enzyme and reduction of StAR mRNA expression.

Is Fournier's gangrene severity index useful for predicting outcome of Fournier's gangrene?

OBJECTIVES: Fournier's gangrene (FG) is a rare but life-threatening disease. Although antibiotics and aggressive debridement have been broadly accepted as the standard treatment, the mortality rate remains high. We conducted a retrospective study to analyze the outcome and identify the risk factors and prognostic indicators. METHODS: We retrospectively reviewed the medical records of 25 patients diagnosed with FG between July 1993 and August 2003. Data collected included age, predisposing factors, treatment modalities, length of hospital stay, surgical debridement times, and outcome. The FG severity index was used to predict outcome. Univariate analysis of the different prognostic factors was performed using t test and Fisher's exact probability test. RESULTS: All patients were male, 60% were diabetic, and the mean age was 55.8 years. The mean hospital stay was 20 days and the mortality rate was 32%. The mean age of 53.8+/-18.3 (SD) years in the survival group (n=17) was significantly lower than the 59.9+/-10.2 years (n=8) of the non-survival group (p<0.05). Non-survival group patients had lower serum hematocrit (mean 28.9, p=0.019) and albumin (mean 1.93, p=0.024) levels. In our series, the mean FG severity index for survivors was 4.41+/-2.45 (range 2-9) compared to 12.75+/-2.82 (range 9-18) for those who died (t test, p<0.0001). CONCLUSION: The survival rate of younger patients with FG was higher. We agree that a FG severity index cutoff value of 9 is an excellent predictor of outcome.