Use of cell-free circulating schistosome DNA in serum, urine, semen, and saliva to monitor a case of refractory imported schistosomiasis hematobia.

This case of imported refractory schistosomiasis has highlighted the usefulness of cell-free parasite DNA as a diagnostic marker to assess active schistosome infection. In contrast to the rapid disappearance of ova in urine, parasite DNA remained persistent in several other specimen types even after the fourth treatment with praziquantel. This result was consistent with the presence of morphologically intact ova in bladder biopsy samples and with the corresponding symptoms.

Role of the Small GTPase Rho3 in Golgi/Endosome trafficking through functional interaction with adaptin in Fission Yeast.

BACKGROUND: We had previously identified the mutant allele of apm1(+) that encodes a homolog of the mammalian µ1A subunit of the clathrin-associated adaptor protein-1 (AP-1) complex, and we demonstrated the role of Apm1 in Golgi/endosome trafficking, secretion, and vacuole fusion in fission yeast. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we isolated rho3(+), which encodes a Rho-family small GTPase, an important regulator of exocystosis, as a multicopy-suppressor of the temperature-sensitive growth of the apm1-1 mutant cells. Overexpression of Rho3 suppressed the Cl(-) sensitivity and immunosuppressant sensitivity of the apm1-1 mutant cells. Overexpression of Rho3 also suppressed the fragmentation of vacuoles, and the accumulation of v-SNARE Syb1 in Golgi/endosomes and partially suppressed the defective secretion associated with apm1-deletion cells. Notably, electron microscopic observation of the rho3-deletion cells revealed the accumulation of abnormal Golgi-like structures, vacuole fragmentation, and accumulation of secretory vesicles; these phenotypes were very similar to those of the apm1-deletion cells. Furthermore, the rho3-deletion cells and apm1-deletion cells showed very similar phenotypic characteristics, including the sensitivity to the immunosuppressant FK506, the cell wall-damaging agent micafungin, Cl(-), and valproic acid. Green fluorescent protein (GFP)-Rho3 was localized at Golgi/endosomes as well as the plasma membrane and division site. Finally, Rho3 was shown to form a complex with Apm1 as well as with other subunits of the clathrin-associated AP-1 complex in a GTP- and effector domain-dependent manner. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings reveal a novel role of Rho3 in the regulation of Golgi/endosome trafficking and suggest that clathrin-associated adaptor protein-1 and Rho3 co-ordinate in intracellular transport in fission yeast. To the best of our knowledge, this study provides the first evidence of a direct link between the small GTPase Rho and the clathrin-associated adaptor protein-1 in membrane trafficking.

Development of a nomogram for predicting high-grade prostate cancer on biopsy: the significance of serum testosterone levels.

BACKGROUND: A screening method that focuses on the early detection of high-grade prostate cancer is required. In this study, two sets of nomograms were developed, one to predict the presence of prostate cancer, and the other to predict the presence of high-grade prostate cancer (defined as Gleason Score > or =7). PATIENTS AND METHODS: Prostate biopsies were obtained from 396 men with an abnormal serum level of prostate-specific antigen (PSA). Using factors including age, PSA, follicle stimulating hormone (FSH), serum teststerone level and prostate volume of the transitional zone (TZ), nomograms were created that incorporated these factors. External validations were performed involving 174 males, including 103 normal and 71 prostate cancer cases from our institution. RESULTS: Out of the 396 patients referred for prostate biopsy, 146 were found to have prostate cancer. On logistic regression analysis, age, PSA, prostate volume of the TZ and FSH were significant predictors of prostate cancer, while serum PSA, and testosterone levels were significant predictors of high-grade prostate cancer. The pretreatment testosterone level was found to be a significant biomarker for predicting the pathological features. CONCLUSION: The testosterone level might be a useful biomarker to be included in conventional PSA screening programs to further improve the efficacy of detecting potentially lethal carcinomas.

DNA damage response in prostate cancer cells after high-intensity focused ultrasound (HIFU) treatment.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a new modality that can be used for local tumor ablation therapy. In the present study, the expression of human checkpoint kinase2 (Chk2), which may have significant roles in the response to DNA damage after HIFU treatment for prostate cancer, was examined. MATERIALS AND METHODS: By immunohistochemistry, the Chk2 expression in human prostate cancer tissues was examined before and after HIFU treatment. The phosphorylation of ataxia-telangiectasia-mutated kinase (ATM), histone H2A variant (H2AX), Chk2 and p53, and the number of apoptotic cells in human prostate cancer cell lines after heat treatment was checked. RESULTS: The expression level of phosphorylated Chk2 was found to be increased after HIFU treatment. In addition, heat treatment induced the phosphorylation of Chk2 proteins examined and led to apoptosis in the prostate cancer cells. CONCLUSION: Our results suggest that DNA double-strand break formation is a possible pathway of HIFU treatment and leads to heat-induced cell killing.

Salivary 8-OHdG: a useful biomarker for predicting severe ED and hypogonadism.

INTRODUCTION: Erectile and endothelial dysfunction are common pathologies of multiple cardiovascular risk factors and are considered longitudinal predictors of cardiovascular events. Oxidative stress and decreases in testosterone levels play an important role in the pathogenesis of endothelial dysfunction. AIM: We sought to determine whether the severity of erectile dysfunction (ED) was associated with individual levels of testosterone and oxidative stress, and whether treatment with a phosphodiesterase type 5 inhibitor could reduce oxidative stress and increase testosterone availability. METHODS: We evaluated the association of salivary 8-hydroxy-2'-deoxyguanosine (8-OHdG), salivary testosterone, International Index of Erectile Function-erectile function domain (IIEF-EF) scores, and Medical Outcome Study (MOS) 36-item Short-Form Healthy Survey (SF-36) questionnaires in 128 middle-aged male volunteers. We investigated the changes in testosterone levels, salivary 8-OHdG levels, IIEF-EF scores, and SF-36 scores in 20 ED patients (according to the IIEF-EF) who took 50 mg of sildenafil once a week for 6 months. MAIN OUTCOME MEASURES: IIEF-EF scores were used to assess ED severity. Antioxidant status was defined by salivary 8-OHdG. Salivary testosterone was used to evaluate serum bioavailable testosterone availability. RESULTS: Salivary 8-OHdG (OR = 9.88, 95% CI: 1.52-64.10), salivary testosterone (Odds ratio [OR] = 0.96, 95% CI: 0.93-0.98), and vitality on the SF-36, version 2 (SF-36 v2) (OR = 0.92, 95%CI: 0.84-0.98) were significantly associated with the severity of ED in healthy volunteers. Treatment with sildenafil for 6 months significantly increased the total serum testosterone (426.4 +/- 174.8 vs. 569.6 +/- 146.1 ng/dL, P = 0.021) and salivary testosterone levels (56.1 +/- 22.3 vs. 110.0 +/- 48.4 pg/mL, P < 0.001), whereas it decreased salivary 8-OHdG levels (2.30 +/- 0.23 vs. 0.90 +/- 0.05 ng/mL, P = 0.0046). CONCLUSIONS: Salivary 8-OHdG is a useful biomarker for predicting severe ED and hypogonadism in middle-aged men. Once-a-week treatment with sildenafil can have beneficial effects on men's health by decreasing oxidative stress and increasing testosterone levels.

Testosterone decreased urinary-frequency in nNOS-deficient mice.

To observe the effect of testosterone on the frequency of urination in mice lacking neuronal nitric oxide synthase (nNOS(-/-)), we compared the urination patterns between unanaesthetized male wild-type (n = 27) and nNOS(-/-) mice (n = 50) with or without testosterone treatment. Compared with wild-type mice, nNOS(-/-) mice showed a greater frequency of urination during a 24-h observation period (3.0 vs. 5.4 times/day, p < 0.0001) without any significant difference in the total voided volume or the functional voiding capacity. While testosterone treatment did not affect the urination patterns in wild-type, it decreased the daytime frequency of urination (5.4 vs. 3.7 times, p = 0.0198) and the nighttime urination (4.4 vs. 2.9 times, p = 0.039) in nNOS(-/-) mice. The nNOS(-/-) mice can be a useful animal model for urinary frequency. Testosterone improved the functional abnormalities in the voiding of nNOS(-/-) mice.

Anesthesia for extracorporeal shockwave lithotripsy: Teikyo University Hospital experience using the third generation lithotripter.

A single-board certified urologist with training and experience in anesthesiology was assigned to treat 502 patients (185 with renal stones, 317 with ureteral stones) using the Dornier Compact Delta lithotripter under general or epidural anesthesia. Data were obtained regarding stone location, stone size, shockwave use, stone-free rate, and complications. In all, 502 stones were treated with the Dornier Compact Delta lithotripter. Among renal stones, 73% were in the renal pelvis. Among ureteral stones, 60% were in the upper, 10% in the middle, and 30% in the lower ureter. Diameters of 61.8% of stones were less than 1 cm. The mean number of shocks was 3,471 at a mean power setting of 5. The stone-free rate for renal stones was 71.5%, while for ureteral stones this reached 99%. The efficiency quotient was calculated as 0.65. One patient with a renal stone developed perinephric hematoma requiring 3 units of transfusion. With a success rate higher than that reported for other lithotripters, the Dornier Compact Delta lithotripter represents a feasible treatment for urolithiasis. We stress that even in the third generation machines the lithotripsy under anesthesia can improve the treatment efficacy.

[Hormone replacement Up-to-date. LOH and testosterone replacement therapy: clinical application].

Promoting health and preventing disease requires a thorough understanding of the complexity of social and behavioral factors that affect the health of individuals and condition of communities. The concept of age-related androgen deficiency in men, also termed late-onset hypogonadism (LOH) has opened up public awareness of the significance of men's health. Low testosterone levels affect physical, mental and sexual activities, manifesting a loss of muscle mass and bone strength, increased body fat, decreased energy, less interest in sex, erectile dysfunction, irritability and depression. Although testosterone replacement therapy is needed for LOH, holistic approach including changing herbal medicine, lifestyle, proper diet, regular exercise, good relationship with the partner should be considered.