Search

Summary The objective of this study was to characterise the status of health-related quality of life (HRQOL) in Japanese men with late-onset hypogonadism (LOH) treated with testosterone replacement therapy (TRT). HRQOL in 69 consecutive Japanese men with LOH undergoing TRT for at least 6 months was prospectively evaluated before and 6 months after the initiation of TRT using the Medical Outcomes Study 8-Item Short-Form Health Survey (SF-8). All eight-scale scores except for bodily pain (BP) in the 69 patients at 6 months after the introduction of TRT significantly improved compared with those before TRT; however, all scale scores except for BP in the 69 patients were significantly inferior to those in age-matched Japanese controls irrespective of the timing of SF-8. Multivariate analyses of several parameters revealed that both age and Aging Male Symptom (AMS) score had an independent impact on mental health (MH), despite the lack of an independent association between any score and the remaining factors examined. TRT appeared to significantly improve the status of HRQOL in men with LOH; however, even after the introduction of TRT, HRQOL associated with MH remained significantly impaired in elderly men and/or those with a high AMS score.

The objectives of this study were to determine whether the inhibition of clusterin expression in rat Sertoli cells enhances heat stress-induced apoptosis. The scrotums of rats were immersed in a water bath of 43 °C for 15 min. Testicular weight and germ cell number markedly decreased after the heat treatment in a time-dependent manner. In contrast, clusterin mRNA and protein expression levels were significantly up-regulated and peaked on day 21. The apoptotic index was markedly increased 1 day after the heat treatment. We then purified Sertoli cells from the rat testes, and an expression vector containing siRNA targeting the clusterin gene was transiently transfected into Sertoli cells. Following exposure to heat stress at 41 °C for 12 h, clusterin mRNA was markedly up-regulated after transfection with the control vector; however, the transfection of siRNA targeting the clusterin resulted in >70% reduction in the expression of clusterin mRNA. Furthermore, the apoptotic index in these Sertoli cells was significantly higher after the treatment with siRNA targeting the clusterin than control, and the most prominent difference was observed within 24 h after the heat treatment. These results suggest that an increase in the secretion of clusterin by Sertoli cells protects the testes from heat stress-induced injury.

This study aimed to investigate the effects of testosterone replacement therapy (TRT) on lower urinary tract symptoms (LUTS) in men with late-onset hypogonadism (LOH) and to identify parameters predicting the efficacy of TRT in improving LUTS. This study included 60 consecutive Japanese men who were diagnosed with LOH and subsequently received TRT between January 2009 and December 2014. In this series, 250 mg of testosterone was injected intramuscularly every 3 or 4 weeks in all patients. The following parameters were retrospectively reviewed: body mass index (BMI), Aging Male Symptom (AMS) score, International Prostate Symptom Score (IPSS), International Index of Erectile Function–5 (IIEF-5) score, residual urine volume, prostate volume, serum levels of the prostate-specific antigen (PSA), and total- and free-testosterone levels before and 6 months after TRT. No significant differences were observed in BMI, residual urine volume, or prostate volume between surveys before and after TRT. The AMS score, IPSS, and IIEF-5 score were significantly improved and significant increases were noted in the serum levels of PSA and total- and free-testosterone levels after TRT. An analysis of IPSS subscores documented the significant improvement in storage symptom scores, but not in voiding symptom scores after TRT. Multivariate analyses of parameters assessed in this study identified the pretreatment AMS score, posttreatment IIEF-5 score, and prostate volume as independent predictors of improvements in IPSS following TRT. This study revealed that TRT appeared to have considerable therapeutic effects on LUTS, particularly on storage symptoms, in men with LOH.

Although obesity is recognized to be a risk factor for chronic kidney disease (CKD), few studies have reported the association between obesity and CKD in the young population. We investigated the relationship between obesity and renal function including proteinuria in young Japanese.This cross-sectional study consisted of 16,031 men and 5,746 women aged from 20 to 39 years who received health examinations. The subjects were stratified into four age groups (20-24, 25-29, 30-34, and 35-39 years) or into four groups based on the number of risk factors (hypertension, hyperglycemia, dyslipidemia, and hyperuricemia). The relationship between obesity and risk factors and the relationship between obesity and estimated glomerular filtration rate (eGFR) were analyzed.There were no significant differences in eGFR between obese and nonobese groups, except in the male 35-39 years age group. Body mass index (BMI) in both men and women increased with increase in number of risk factors (P0.001). Multivariate analysis revealed that hypertension, hyperglycemia, dyslipidemia, and hyperuricemia were independently associated with obesity. Obesity and the risk factors were independently associated with proteinuria.The present study indicated that obesity was an independent risk factor for proteinuria in healthy subjects younger than 40 years of age. The other risk factors were independently associated with obesity. These findings suggest that obesity causes proteinuria concomitantly with other risk factors such as hypertension, diabetes, and dyslipidemia in young adults.

Summary The objective of this study was to assess the impact of seminal clusterin level on spermatogenesis in infertile men. This study included 89 men who visited our clinic due to infertility, consisting of 28, 33, and 28 diagnosed with normospermia, oligozoospermia and nonobstructive azoospermia (NOA) respectively. The seminal clusterin concentrations measured by enzyme-linked immunosorbent assay were 47.9, 28.2 and 18.4 ng ml−1 in men with normospermia, oligozoospermia and NOA, respectively, with significant differences among these three groups (P

Recent reports suggest the relationship of short-term blood pressure (BP) variability to cardiovascular target organ damage. In this study, short-term BP variability was assessed as the standard deviation of daytime and nighttime BP in 36 hospitalized patients with chronic renal failure (CRF) who underwent ambulatory BP monitoring. Positive correlations were observed between body mass index (BMI) and daytime systolic and diastolic BP variability, BMI and nighttime diastolic BP variability, cholesterol and daytime systolic BP variability, cholesterol and nighttime systolic and diastolic BP variability, nocturnal decline in BP and nighttime diastolic BP variability, and plasma concentration of norepinephrine (p-NE) and nighttime systolic BP variability. In multivariate linear regression analyses, BMI showed the strongest association with daytime and nighttime diastolic BP variability (p < .005 and p < .05). On the other hand, cholesterol and p-NE were the primary determinants of daytime and nighttime systolic BP variability, respectively (p < .01 and p < .0005). Interestingly, CRF patients with ischemic heart disease (IHD) had significantly increased daytime systolic and diastolic BP variability and nighttime systolic BP variability (p < .05 or less). Furthermore, logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor of IHD in patients with CRF (odds ratio 1.50 [95% confidence interval 1.01 to 2.25]; p < .05). Taken together, short-term BP variability is suggested to be affected by BMI, cholesterol, and p-NE in CRF patients. Furthermore, sympathetic nerve overactivity may be involved in cardiovascular complications in CRF patients through the increase in nighttime systolic BP variability.

We report pregnancy with the delivery of a healthy child by TESE-ICSI 7 years after bilateral adult orchidopexy. A 29-year-old patient presented with infertility and previous bilateral cryptorchidism, but no surgical treatment had ever been performed. His partner had been assessed by a gynaecologist, and no contributing female factors were detected. Orchidopexy and conventional testicular sperm extraction (TESE) were performed and microdissection TESE 10 months after orchidopexy. The second microdissection TESE with intracytoplasmic sperm injection (ICSI) was performed 7 years after orchidopexy. The couple achieved pregnancy with the delivery of a healthy child by TESE-ICSI. It is concluded that bilateral orchidopexy in adulthood progresses spermatogenesis gradually, and microdissection TESE may succeed after a certain period of time following treatment.

In cultured vascular smooth muscle cells (VSMCs), interleukin-1beta (IL-1beta) stimulates inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. IL-1beta also activates phospholipase A2 (PLA2), and induces lipoxygenase (LOX) and cyclooxygenase-2 (COX-2). The present study investigated whether these metabolites are involved in the regulation of IL-1beta-induced NO production and iNOS expression. Pretreatment with ONO-RS-082, the secretory PLA2 (sPLA2) inhibitor, at 1 to 10 micromol/l reduced IL-1beta-stimulated nitrite production and iNOS expression. Nordihydroguaiaretic acid (NDGA, 1 to 10 micromol/l), the LOX inhibitor, also reduced IL-1beta (10 ng/ml)-stimulated nitrite production and iNOS expression in a dose-dependent manner. Exogenous 12(S)-hydroxyeicosatetraenoic acids (HETE) enhanced the IL-1beta-stimulated nitrite production and iNOS expression. On the other hand, the COX inhibitors, indomethacin and NS-398, had little effect on nitrite production or iNOS expression. These results suggest that LOX products play important roles in the regulation of stimulus-induced NO production in VSMCs.

Prevention of osteoporosis and renal osteodystrophy are important for the long-term quality of life in dialysis patients. We examined whether administration of menatetrenone (vitamin K2) improves bone metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients. Administration of a single dose of menatetrenone (15 mg) revealed that the 24-h pharmacodynamics in CAPD patients were comparable to those in control individuals. In a 12-month period of oral menatetrenone administration (45 mg/day), eight stable CAPD patients were studied for blood-bone metabolism parameters and for bone mineral content. Blood concentration of menatetrenone was detectable during the experiment period. Only at 12 months did active vitamin D3 and bone-type alkaline phosphatase (ALP) fall significantly, while total ALP rose significantly. Bone mineral density measured by dual-energy X-ray absorptiometry remained at the same level throughout the study period, suggesting that menatetrenone may protect against bone mineral loss in CAPD patients. These results show that the same dose of oral menatetrenone can be given to CAPD patients as to control individuals, and that menatetrenone can be used safely for 1 year in CAPD patients.

A retroperitoneal laparoscopic approach was found to be useful for treating primary retroperitoneal tumors located below the level of the renal vessels., Background: Inflammatory pseudotumors were mostly encountered in the lung. Retroperitoneal inflammatory pseudotumors are relatively rare. Although laparoscopic surgery with a modified flank position is widely performed for retroperitoneal tumors, we placed the patient in the supine position to maintain the normal anatomical view of the retroperitoneal space. We report a case of retroperitoneal inflammatory pseudotumor extracted via retroperitoneoscopic surgery in the supine position. Methods and Results: A 53-year-old man presented with back pain and frequent urination. Ultrasonographic examination revealed a solid tumor above the urinary bladder. This tumor was diagnosed as a primary retroperitoneal tumor by computed tomography, magnetic resonance imaging, and angiography. The retroperitoneoscopic procedure was adopted to remove this tumor. Histopathologic examination revealed an inflammatory pseudotumor. There was no evidence of recurrence 5 years after surgery. Conclusions: The diagnosis of the inflammatory pseudotumor is rarely made before histologic examination. Only pathologic examination allows the correct diagnosis. Consequently, most patients undergo surgical treatment. A recurrence rate of 25% has been reported for inflammatory pseudotumors. Thus, radical resection is needed. The retroperitoneal laparoscopic approach with the patient in the supine position is useful for surgically treating these primary retroperitoneal tumors located below the level of the renal vessels.

Objective To characterize the changes in seminogram findings in infertile men after varicocelectomy. Methods This study included 71 consecutive infertile men who underwent microsurgical low ligation varicocelectomy and received 3 semen analyses, 1 before microsurgical varicocelectomy and again at 3 and 12 months after. Total motile sperm count (TMSC) was calculated using the following formula: [volume (mL) × concentration (millions/mL) × motility (%)]. Results Despite the lack of significant changes in the proportion of sperm with abnormal morphology, sperm concentration, motility, and TMSC in the 71 patients were significantly higher at 3 and 12 months after varicocelectomy than before surgery. However, no further improvement in these parameters at 12 months after varicocelectomy was noted compared with those at 3 months. Furthermore, when the included men were divided into 3 groups according to preoperative TMSC as 9 million, TMSCs at 3 months after varicocelectomy in all 3 groups were significantly higher than those before varicocelectomy; however, TMSCs at 12 months after surgery in all groups were similar to those at 3 months. Conclusion The level of improvement in semen parameters at 3 months after varicocelectomy may be stable at 12 months after surgery, irrespective of baseline values of TMSC. Therefore, varicocelectomy could be offered as a therapeutic option for infertile men, even for couples with an older woman, because its efficacy is evaluable at 3 months after surgery, and assisted reproductive technology could be immediately applied to ineffective cases.

The expression of exogenous DNA in Sertoli cells is essential for studying its functional genomics, pathway analysis, and medical applications. Electroporation is a valuable tool for nucleic acid delivery, even in primarily cultured cells, which are considered difficult to transfect. In this study, we developed an optimized protocol for electroporation-based transfection of Sertoli cells and compared its efficiency with conventional lipofection. Sertoli cells were transfected with pCMV-GFP plasmid by square-wave electroporation under different conditions. After transfection of plasmid into Sertoli cells, enhanced green fluorescent protein (EGFP) expression could be easily detected by fluorescent microscopy, and cell survival was evaluated by dye exclusion assay using Trypan blue. In terms of both cell survival and the percentage expressing EGFP, 250 V was determined to produce the greatest number of transiently transfected cells. Keeping the voltage constant (250 V), relatively high cell survival (76.5% ± 3.4%) and transfection efficiency (30.6% ± 5.6%) were observed with a pulse length of 20 μm. The number of pulses significantly affected cell survival and EGFP expression (P0.001). Cell survival clearly decreased following one to three pulses, from 83.9% ± 6.1% to 3.2% ± 1.1%, with EGFP expression increasing from 41.8% ± 9.4% to 66.7% ± 5.2%. The yield of positive cells increased with increasing concentration of plasmid DNA (range, 10-50 μg/ml), from 14.0% ± 2.8% to 35.0% ± 6.3%, but cell viability steadily decreased following 20 μg/ml plasmid DNA, from 73.1% ± 4.9% to 57.0% ± 6.6%. Compared with two popular cationic lipid transfection methods, the transfection efficiency of electroporation (21.5% ± 5.7%) was significantly higher than those of Lipofectamine 2000 (2.9% ± 1.0%) and Effectene (1.9% ± 0.8%) in this experiment (P0.001). We describe the process of optimizing electroporation conditions, and the successful electroporation of plasmid DNA into primarily cultured Sertoli cells. Our results indicate that the method of electroporation is more suitable than other approaches for the transfection of Sertoli cells.

Varicocele is currently the most common irregularity identified in males that is associated with impaired spermatogenesis. It primarily presents in the form of decreased sperm count and motility, abnormal morphology, and significantly increased sperm DNA fragmentation. Several studies have shown that surgical repair improves semen parameters and increases the odds of spontaneous pregnancy. However the exact effect of surgical repair treatment remains controversial. Therefore, the aim of our study was to evaluate the effectiveness of microsurgical repair by comparing common semen parameters and sperm DNA fragmentation index (DFI). We evaluated infertile men (n = 19) who underwent microsurgical subinguinal varicocelectomy for treatment of clinical varicocele before and 3 months after surgery. Normozoospermic men (n = 19) were considered as the normal control group. Semen parameters improved significantly after surgery when compared with that before surgery, but still significant differences with the normal control group were observed. In comparison, sperm DNA integrity improved significantly after surgery (percentage DFI decreased from 28.4 ± 15.6% before surgery to 22.4 ± 12.9%, at 3 months post surgery) to similar levels as the normal control group. These results suggest that microsurgical repair may be considered as a treatment option in infertile men with palpable varicocele.

To evaluate the effect of surgical intervention on catch-up growth as determined by a decreased testicular volume discrepancy in children and adolescents with varicocele.A systematic search was performed using MEDLINE and the PubMed database and cross-referenced as of October 28, 2011 using the terms "varicocele," "children," "adolescent," "surgery," and "testicular volume." All relevant studies were of the testicular volume discrepancy variance before and after surgical repair. The outcomes included the number of patients with initial testicular atrophy and those with catch-up growth after surgical repair. The database search, quality evaluation, and data extraction were independently performed by 2 reviewers.Of 75 studies, 14 were included for analysis and involved 1475 patients. The combined analysis showed that the testicular volume discrepancy was significantly reduced after surgery in the ≥10% group (P.00001) and ≥20% group (P.00001), respectively. No difference was found between the 2 groups (P = .70). Taken together, the number of patient with testicular volume disproportion in all pediatric and adolescent varicocele patients significantly decreased after surgery (P.00001). The average proportion of catch-up growth was 76.4% (range 52.6%-93.8%).The meta-analysis suggested clear advantages of surgical intervention on reducing testicular hypotrophy when the discrepancy is ≥10% in children and adolescents with varicocele. Additional prospective and controlled studies are warranted to elucidate the treatment of children and adolescents with varicocele.

To determine the effect of surgical varicocele repair in improving testicular Leydig cell function as shown by increased testosterone production.Eligible studies were searched in Medline and the Pubmed database, and cross-referenced as of 31 May 2011 using the terms "varicocele,""testosterone" and "surgery." The database search, quality assessment and data extraction were independently carried out by two reviewers. Only studies including patients with testosterone evaluation before and after surgery were considered for the analysis. A systematic review and meta-analysis was carried out for continues variables using random effect models.Out of 125 studies, a total of nine were selected, including 814 patients. The combined analysis showed that mean serum testosterone levels after surgical treatment increased by 97.48 ng/dL (95% confidence interval 43.73-151.22, P=0.0004) compared with preoperative levels.Surgical treatment of varicocele significantly increases testosterone production and improves testicular Leydig cell function.

Aims: The present study was designed to examine the role of the renin-angiotensin system in the regulation of macula densa cyclooxygenase-2 (COX-2) during altered dietary salt intake. Methods: We investigated COX-2 expression in the macula densa of angiotensinogen gene-knockout (Atg–/–) mice. COX-2 expression in the renal cortex was determined by real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. Results: The renal cortical expression of COX-2 mRNA increased 24.7 times in Atg–/– mice compared with Atg+/+ mice. When Atg--/– mice were fed a high-salt diet (4% NaCl) for 10 days, the levels of COX-2 expression were markedly suppressed. The macula densa COX-2 immunoreactivity was correlated with the mRNA expression. The selective inhibition of neuronal isoform of nitric oxide synthase (N-NOS) activity by 7-nitroindazole significantly reduced the levels of COX-2 mRNA in Atg–/– mice by 54.1%. Conclusion: These results suggest that (1) COX-2 activity in the macula densa can be regulated by salt intake through a mechanism independent of the renin-angiotensin system, and (2) COX-2 expression is functionally linked to renal cortical N-NOS activity in Atg–/– mice.