Gut microbiota and the prevalence and incidence of renal stones.

The role of the gut microbiome in the development of renal stone diseases has not been well characterized. This study focused on the taxonomic and functional profiles of gut microbiomes according to the prevalence and incidence of nephrolithiasis. Stool samples from 915 Korean adults were collected at baseline. Participants were followed for a median of 4.0 years. We evaluated the biodiversity of the gut microbiota and taxonomic profiles associated with nephrolithiasis status, using 16S rRNA gene sequencing. Nephrolithiasis status was categorized into three groups: control (no-stone at both baseline and follow-up visits), incidental nephrolithiasis, and prevalent nephrolithiasis. Compared to the control and incidental nephrolithiasis, the prevalent nephrolithiasis showed a reduced evenness in alpha diversity. Nephrolithiasis was associated with a reduced abundance of some key taxa involved in short-chain fatty acid production. Moreover, the abundance of Bifidobacterium, which possess oxalate-degrading ability, was higher in the control. Conversely, there was no significant difference in the bacterial composition between the incidental and prevalent nephrolithiasis. In our study with repeated nephrolithiasis measurements, prevalent renal stones were associated with an altered gut microbiota composition compared to the control. Besides the known oxalate degradation pathway, other functional pathways inferred in this study require further investigation.

Analysis of Sexual Behaviors among Adults in Korea: Results from the "Korean National Survey on Sexual Consciousness".

PURPOSE: This study aimed to understand the characteristics of sexual behaviors among Korean adults to facilitate the development of strategies and policies focused on sexual health in groups categorized by sociodemographic characteristics. MATERIALS AND METHODS: A nationally representative probability sample of 2,500 individuals (1,273 men and 1,227 women) aged 18-69 years obtained using a stratified multiple-stage sampling method based on Statistics Korea (KOSTAT) participated in a cross-sectional online survey. The survey consisted of structured questionnaires comprising questions on demographic information, lifetime sexual behavior, and sexual behavior in the previous 12 months. RESULTS: The mean age at first sexual intercourse was lower in men than in women (21.9±4.4 vs. 24.1±4.4 years, p=0.001). The overall prevalence rate of sexual events with casual partners within previous 12 months was 13.1% (95% confidence interval [CI], 11.6%-14.5%). It was found to more commonly exist among lower age groups and men. The overall regular condom use rates with relationship partner and casual partner were 14.8% (95% CI, 13.2%-16.4%) and 39.6% (95% CI, 33.9%-45.3%), respectively. Condom use rate with casual partners among 20s and 30s men was 51.2%. Overall, only 10.4% of the respondents had received sexual education about sexually transmitted infections. CONCLUSIONS: This study provided contemporary sexual behaviors in Korean adults, and identified socio-demographic factors that seem to influence sexual behaviors. Low condom use rates and low rate of receiving sexual education were concerns. The result of this study would be useful to health professionals to formulate policies and strategies related to sexual health.

Glycemic Status, Insulin Resistance, and the Risk of Nephrolithiasis: A Cohort Study.

RATIONALE & OBJECTIVE: The effect of glycemic status on nephrolithiasis risk remains controversial. This study sought to examine the association of glycemic status and insulin resistance with incident nephrolithiasis. STUDY DESIGN: A retrospective cohort study. SETTING & PARTICIPANTS: 278,628 Korean adults without nephrolithiasis who underwent a comprehensive health examination between 2011 and 2017. EXPOSURES: Glucose level, glycated hemoglobin level, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). OUTCOME: Nephrolithiasis ascertained using abdominal ultrasound. ANALYTICAL APPROACH: A parametric proportional hazard model was used to estimate adjusted HRs and 95% CIs. We explored prespecified potential sex differences in the association of glycemic status and incident nephrolithiasis. RESULTS: During a median follow-up of 4.2 years, 6,904 participants developed nephrolithiasis. Associations between levels of glycemic status and incident nephrolithiasis were examined separately in men and women (P for interaction = 0.003). Among men, multivariable-adjusted HRs for incident nephrolithiasis comparing glucose levels of 90-99, 100-125, and ≥ 126 mg/dL were 1.10 (95% CI, 1.01-1.19), 1.11 (95% CI, 1.02-1.21), and 1.27 (95% CI, 1.10-1.46), respectively, while HRs for incident nephrolithiasis comparing glycated hemoglobin levels of 5.7%-5.9%, 6.0%-6.4%, and 6.5%-<5.7% were 1.03 (95% CI, 0.96-1.10), 1.18 (95% CI, 1.07-1.31), and 1.20 (95% CI, 1.06-1.37), respectively. The HR for incident nephrolithiasis comparing the highest HOMA-IR quintile to the lowest quintile was 1.18 (95% CI, 1.06-1.31). Among women, no apparent association was found between glycemic status and nephrolithiasis risk. LIMITATIONS: Glucose tolerance testing and computed tomography assessment for nephrolithiasis were not available. CONCLUSIONS: Higher glycemic values, even within the normoglycemic range, and HOMA-IR were positively associated with increased risk for nephrolithiasis, associations that were only observed among men. Insulin resistance and hyperglycemia may contribute to the development of nephrolithiasis, particularly among men.

Prostate-Specific Antigen Within the Reference Range, Subclinical Coronary Atherosclerosis, and Cardiovascular Mortality.

RATIONALE: Although PSA (prostate-specific antigen)-a tumor marker for prostate cancer-has been reported to be associated with cardiovascular disease (CVD) risk factors, studies on the association of PSA with subclinical and clinical CVD remain limited. OBJECTIVE: We examined the association of total serum PSA within the reference range with coronary artery calcium (CAC) score and CVD mortality. METHODS AND RESULTS: A cross-sectional study was performed in 88 203 Korean men who underwent a health checkup exam including cardiac tomography estimation of CAC score. Logistic regression model was used to calculate odds ratios with 95% CIs for prevalent CAC. PSA levels were inversely associated with the presence of CAC. After adjusting for potential confounders, multivariable-adjusted odds ratio (95% CIs) for prevalent CAC comparing PSA quartiles 2, 3, and 4 to the first quartile were 0.96 (0.90-1.01), 0.88 (0.83-0.93), and 0.85 (0.80-0.90), respectively ( P for trend, <0.001). A cohort study was performed in 243 435 Korean men with a mean age of 39.3 years, PSA values of <4.0 ng/mL, and without known CVD or prostate disease who were followed up with for ≤14 years for CVD mortality (median, 7.3 years). CVD deaths were ascertained through linkage to national death records. Hazard ratios and 95% CIs for CVD mortality were estimated using Cox proportional hazards regression analyses. During 1 829 070.1 person-years of follow-up, 336 CVD deaths were identified. After adjustment for potential confounders, multivariable-adjusted hazard ratios (95% CIs) for CVD mortality comparing PSA quartiles 2, 3, and 4 to the lowest quartile were 0.90 (0.66-1.22), 0.79 (0.58-1.08), and 0.69 (0.51-0.93), respectively. CONCLUSIONS: Serum total PSA levels within the reference range showed an inverse association with subclinical atherosclerosis and CVD mortality in young and middle-aged Korean men, indicating a possible role of PSA as a predictive marker for subclinical and clinical CVD.

Metabolically healthy and unhealthy obesity phenotypes and risk of renal stone: a cohort study.

BACKGROUND/OBJECTIVES: Although obesity is considered an independent risk factor of nephrolithiasis, little is known about the effect of obesity on nephrolithiasis according to metabolic health status. We investigated the association between body mass index (BMI) category and the incidence of nephrolithiasis in metabolically healthy and unhealthy individuals. SUBJECTS/METHODS: The cohort consisted of 270,190 Korean adults free of nephrolithiasis at baseline, who were followed-up annually or biennially for a median of 4.1 years. Nephrolithiasis were determined based on ultrasonographic findings. Being metabolically healthy was defined as not having any metabolic syndrome component. A parametric Cox model was used to estimate the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: During 1,415,523.0 person-years of follow-up, 13,450 participants developed nephrolithiasis (incidence rate, 9.5 per 1000 person-years). Obesity was positively associated with an increased risk of incident nephrolithiasis in dose-response manner, but the association was stronger in metabolically healthy individuals. Among metabolically healthy individuals, the multivariable-adjusted HRs (95% CIs) for incident nephrolithiasis comparing BMIs 23-24.9, 25-29.9, and ≥30 with a BMI of 18.5-22.9 kg/m2 as the reference were 1.02 (0.95-1.10), 1.12 (1.03-1.22), and 1.72 (1.21-2.44), respectively, whereas corresponding HRs (95% CIs) in metabolically unhealthy individuals were 1.10 (1.04-1.17), 1.27 (1.20-1.34), and 1.36 (1.22-1.51), respectively. The association between obesity and incident nephrolithiasis was stronger in men and current smokers. CONCLUSIONS: Obesity was associated with a higher incidence of nephrolithiasis in both metabolically healthy and unhealthy individuals, indicating obesity per se as an independent risk factor for nephrolithiasis.

Sitting time, physical activity and the risk of lower urinary tract symptoms: a cohort study.

OBJECTIVES: To examine the association of sitting time and physical activity level with the incidence of lower urinary tract symptoms (LUTS) in a large sample of Korean men. MATERIALS AND METHODS: A cohort study was performed in 69 795 Korean men, free of LUTS at baseline, who were followed up annually or biennially for a mean of 2.6 years. Physical activity level and sitting time were assessed using the validated Korean version of the International Physical Activity Questionnaire Short Form. LUTS were assessed using the International Prostate Symptom Score (IPSS) and clinically significant LUTS were defined as an IPSS score ≥8. RESULTS: Over 175 810.4 person-years, 9 217 people developed significant LUTS (incidence rate, 39.0 per 1 000 person-years). In a multivariable-adjusted model, both low physical activity level and prolonged sitting time were independently associated with the incidence of LUTS. The hazard ratios (95% confidence intervals [CIs]) for incident LUTS comparing minimally active and health-enhancing physically active groups vs the inactive group were 0.94 (95% CI 0.89-0.99) and 0.93 (95% CI 0.87-0.99), respectively (P for trend 0.011). The hazard ratios (95% CIs) for LUTS comparing 5-9 and ≥10 h/day sitting time vs <5 h/day were 1.08 (95% CI 1.00-1.24) and 1.15 (95% CI 1.06-1.24), respectively (P for trend <0.001). CONCLUSIONS: Prolonged sitting time and low physical activity levels were positively associated with the development of LUTS in a large sample of middle-aged Korean men. This result supports the importance of both reducing sitting time and promoting physical activity for preventing LUTS.

Blood Droplet-Based Cancer Diagnosis via Proteolytic Activity Measurement in Cancer Progression.

Matrix metalloproteinase (MMP) is a key marker and target molecule for cancer diagnosis, as MMP is able to cleave peptide chains resulting in degradation of extracellular matrix (ECM), a necessary step for cancer development. In particular, MMP2 has recently been recognized as an important biomarker for lung cancer. Despite the important role of detecting MMP molecules in cancer diagnosis, it is a daunting task to quantitatively understand a correlation between the status of cancer development and the secretion level of MMP in a blood droplet. Here, we demonstrate a nanoscale cancer diagnosis by nanomechanical quantitation of MMP2 molecules under cancer progression with using a blood droplet of lung cancer patients. Specifically, we measured the frequency dynamics of nanomechanical biosensor functionalized with peptide chains mimicking ECM in response to MMP2 secreted from tumors in lung with different metastasis level. It is shown that the frequency shift of the biosensor, which exhibits the detection sensitivity below 1 nM, enables the quantitation of the secretion level of MMP2 molecules during the progression of cancer cells or tumor growth. More importantly, using a blood droplet of lung cancer patients, nanomechanical biosensor is shown to be capable of depicting the correlation between the secretion level of MMP2 molecules and the level of cancer metastasis, which highlights the cantilever-based MMP2 detection for diagnosis of lung cancer. Our finding will broaden the understanding of cancer development activated by MMP and allow for a fast and point-of-care cancer diagnostics.

Impact of treatment with statins on prostate-specific antigen and prostate volume in patients with benign prostatic hyperplasia.

PURPOSE: We investigated the impact on prostate-specific antigen (PSA) and prostate volume (PV) of statin medication for 1 year in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We retrospectively investigated 791 patients in whom BPH was diagnosed. For analysis, the patients were divided into four groups according to their medications: group A, α-blocker; group B, α-blocker+statin; group C, α-blocker+dutasteride; group D, α-blockers+statin+dutasteride. To investigate changes in serum PSA, PV, and total cholesterol, we analyzed the data at the time of initial treatment and after 1 year of medication. RESULTS: After 1 year, group A showed a 1.3% increase in PSA and a 1.0% increase in PV. Group B showed a 4.3% decrease in PSA and a 1.8% decrease in PV. The difference in PV reduction between groups A and B was statistically significant (p<0.001). Group C showed a 49.1% reduction in PSA and a 22.9% reduction in PV. Group D showed a 51.6% reduction in PSA and a 24.5% reduction in PV. The difference in PV reduction between groups C and D was not statistically significant (p=0.762). By use of a multivariate logistic regression model, we found that the probability of PV reduction after 1 year was more than 14.8 times in statin users than in statin nonusers (95% confidence interval, 5.8% to 37.6%; p<0.001). CONCLUSIONS: Statin administration reduced PSA and PV in BPH patients. This finding may imply the improvement of lower urinary tract symptoms and prevention of cardiovascular disease and chemoprevention of prostate cancer with statin treatment.

Tuberculosis of testis and prostate that mimicked testicular cancer in young male soccer player.

Staphylococcus infection was the most common organism found in infection of athletics, and tuberculosis (TB) was rare. Although genitourinary tuberculosis (GUTB) was the most common subtype of extrapulmonary tuberculosis (EPTB) in the past, it was recently reported to account for less than 0.5% of all patients with EPTB and 1.5% of all patients with pulmonary tuberculosis (TB). And, there are few cases reported about concomitant tuberculous infection of testis and prostate. Pubic pain is a common symptom in soccer player and its cause can be difficult to determine. A 25-yr-old male soccer player presented with persistent pubic pain of unknown origin. Incidentally, right testicular mass was detected on physical examination. Computed tomography revealed a multiple enlarged retroperitoneal lymph nodes. Under the clinical diagnosis of a right testicular tumor, right radical inguinal orchiectomy was performed. And prostate biopsy was performed due to elevated serum prostate specific antigen (PSA). Pathologic examination confirmed concomitant TB of testis and prostate.

Wilms' tumor in a horseshoe kidney.

The incidence of horseshoe kidney is about 1 in 400 cases. The presence of Wilms' tumor with a horseshoe kidney is unusual, and the occurrence of Wilms' tumor in a horseshoe kidney is estimated at 0.4 to 0.9% of all Wilms' tumors. We report the case of a 5-year-old boy who presented with a stage IV Wilms' tumor in a horseshoe kidney. The patient was treated with preoperative chemotherapy followed by surgical resection and adjuvant chemotherapy. This case illustrates the role of preoperative chemotherapy for preserving renal function and aims to highlight the multimodality treatment of Wilms' tumor.

Tumor establishment features of orthotopic murine bladder cancer models.

PURPOSE: Animal tumor models are important for the evaluation of novel therapeutic modalities. Since the initial report of an orthotopic bladder tumor model, several modifications have been proposed to improve the tumor take rate. Here we compared the HCl-pretreated and electrocauterization-pretreated orthotopic murine bladder tumor models. MATERIALS AND METHODS: MBT-2 murine bladder cancer cells were transurethrally implanted in the bladder of syngeneic C3H/He mice. The mice were divided into three groups according to pretreatment methods (electrocautery, HCl, and control group) and were subjected to pretreatment before instillation of MBT-2 tumor cells into the bladder. Mice were sacrificed on day 21, and bladders were harvested, weighed, and examined histopathologically. RESULTS: The tumor take rate of the control, electrocautery, and HCl groups was 0%, 54%, and 100%, respectively. The tumor take rate of the HCl group was significantly higher than that of the control group (p<0.01) and the electrocautery group (p=0.01). Pathologic reports revealed that all established bladder tumors were high-grade papillary urothelial carcinomas. CONCLUSIONS: The HCl pretreatment model was a preferable murine bladder tumor model for evaluating further therapeutic interventions.

Efficacy and safety of tamsulosin for the treatment of non-neurogenic voiding dysfunction in females: a 8-week prospective study.

We evaluated the therapeutic effects of tamsulosin for women with non-neurogenic voiding dysfunction. Women who had voiding dysfunctions for at least 3 months were included. Inclusion criteria were age > or =18 yr, International Prostate Symptom Score (IPSS) of > or =15, and maximum flow rate (Q(max)) of > or =12 mL/sec and/or postvoid residuals (PVR) of > or =150 mL. Patients with neurogenic voiding dysfunction or anatomical bladder outlet obstruction were excluded. All patients were classified according to the Blaivas-Groutz nomogram as having no or mild obstruction (group A) or moderate or severe obstruction (group B). After 8 weeks of treatment, treatment outcomes and adverse effects were evaluated. One hundred and six patients were evaluable (70 in group A, 36 in group B). After treatments, mean IPSS, bother scores, Q(max), PVR, diurnal and nocturnal micturition frequencies and scored form of the Bristol Female Lower Urinary Tract Symptoms questionnaire (BFLUTS-SF) were changed significantly. Eighty-nine patients (84%) reported that the treatment was beneficial. The proportion of patients reported that their bladder symptoms caused "moderate to many severe problems" were significantly decreased. No significant difference were observed between the groups in terms of IPSS, bother score, Q(max), PVR, micturition frequency, and BFLUTS-SF changes. Adverse effects related to medication were dizziness (n=3), de novo stress urinary incontinence (SUI) (n=3), aggravation of underlying SUI (n=1), fatigue (n=1). Tamsulosin was found to be effective in female patients with voiding dysfunction regardless of obstruction grade.

Kidney tissue reconstruction by fetal kidney cell transplantation: effect of gestation stage of fetal kidney cells.

Dialysis and kidney transplantation, current therapies for kidney failure, have limitations such as severe complications, donor shortage, and immune-related problems. The development of an alternative treatment for kidney failure is demanded. The present study shows that the transplantation of fetal kidney cells reconstitutes functional kidney tissue, and that the gestation stage of kidney cells influences the kidney reconstitution. Fetal kidney cells were isolated from metanephroi of rat fetuses at various gestation stages and transplanted into the omentum or kidney of immunodeficient mice. Immunophenotype analysis of fetal kidney cells showed apparent expression of stem cell markers. Three weeks after transplantation, histological analyses of retrieved grafts revealed the formation of kidney structures, including fluorescently labeled transplanted cells, suggesting the potential of fetal kidney cells to reconstitute kidney tissues. The grafts retrieved from omentum contained cystic fluids with concentrated solutes. However, transplanted early fetal kidney cells had also differentiated into nonrenal tissues such as bone and cartilage. In addition, transplantation of fetal kidney cells from a later gestation stage resulted in poor kidney structure formation. Kidney-specific genes were strongly expressed in the earlier cell transplants. The cells at an earlier gestation stage had higher colony forming ability than the cells at a later stage. This study demonstrates the reconstitution of kidney tissue by transplanting fetal kidney cells and the presence of an optimal time window in which fetal kidney cells regenerate kidney tissues. Disclosure of potential conflicts of interest is found at the end of this article.

Improvement of kidney failure with fetal kidney precursor cell transplantation.

BACKGROUND: Current therapies for end-stage renal disease have severe limitations. Dialysis is only a temporary treatment and does not restore kidney function. Transplantation is limited by donor organ shortage and immune-related problems. Here, we show that the transplantation of fetal kidney precursor cells reconstitutes kidney tissues, reduces uremic symptoms, and provides life-saving metabolic support in kidney failure animal models. METHODS: Kidney failure was surgically induced by resecting kidneys, leaving approximately 1/6 of the total kidney mass (5/6 nephrectomy). Fetal kidney precursor cells were isolated from metanephroi of E17.5 rat fetuses using collagenase/dispase digestion. Five weeks after the nephrectomy procedure, isolated fetal kidney precursor cells were transplanted under the kidney capsule of rats using fibrin gel matrix. Six and ten weeks after transplantation, animals were analyzed biochemically and the grafts were retrieved for histological analyses. RESULTS: Five weeks after the nephrectomy, glomerular hypertrophy, and increased blood urea nitrogen and serum creatinine levels were observed. The cell transplantation into the kidneys of kidney failure-induced rats resulted in kidney tissue reconstitution and the transplanted cells were observed in the reconstitution region of the kidneys as evidenced by the presence of fluorescently labeled cells. In addition, biochemical parameters from serum and urine samples showed improved kidney functions compared with non-treated group without severe immune response after ten weeks. CONCLUSION: Transplanting fetal kidney precursor cells showed the potential for the partial augmentation of kidney structure and function in the treatment of kidney failure.

What is the indication of varicocelectomy in men with nonobstructive azoospermia?

OBJECTIVES: To investigate the effect of microsurgical varicocelectomy in nonobstructive azoospermic patients. The surgical outcomes were correlated with the histopathologic patterns of testicular specimens. METHODS: A total of 19 nonobstructive azoospermic men who underwent testicular biopsy and varicocelectomy were included in the study. In 15 patients, unilateral varicocelectomy was performed, and in 4, bilateral varicocelectomy was performed. An inguinal approach with a microsurgical technique was used. Postoperative semen analyses were performed in each patient 3 months after varicocelectomy. RESULTS: Testicular histologic examination revealed hypospermatogenesis in 3 patients, maturation arrest in 6, and germ cell aplasia in 10. After a mean follow-up of 7.4 months, motile sperm in the ejaculate was identified in 7 (36.4%) of the nonobstructive azoospermic patients. Of these 7 patients, 2 had hypospermatogenesis, 4 had maturation arrest, and 1 had Sertoli cell-only syndrome. All 7 patients had improvement in their sperm concentration and motility (0.36 x 10(6)/mL and 47.1%, respectively). However, 2 of these 7 patients with motile sperm after varicocelectomy had recurrence of the azoospermic state at their second postoperative semen analysis. Pregnancy was achieved by natural intercourse for 1 of the men (5.3%) with hypospermatogenesis. CONCLUSIONS: Microsurgical varicocelectomy may offer patients with nonobstructive azoospermia an opportunity to have sperm in their ejaculate and even the possibility of natural conception. Microsurgical varicocelectomy can be considered a viable option in selective patients with nonobstructive azoospermia and varicocele, instead of the less cost effective and more bothersome assisted reproductive techniques.

Porcine vesical acellular matrix graft of tunica albuginea for penile reconstruction.

AIM: To characterize the feasibility of the surgical replacement of the penile tunica albuginea (TA) and to evaluate the value of a porcine bladder acellular matrix (BAM) graft. METHODS: Acellular matrices were constructed from pigs' bladders by cell lysis, and then examined by scanning electron microscopy (SEM). Expression levels of the mRNA of the vascular endothelial growth factor (VEGF) receptor, fibroblast growth factor (FGF)-1 receptor, neuregulin, and brain-derived neurotrophic factor (BDNF) in the acellular matrix and submucosa of the pigs'bladders were determined through the reverse transcription-polymerase chain reaction (PCR). A 5 mm X 5 mm square was excised from the penile TA of nine rabbits. The defective TA was then covered in porcine BAM. Equal numbers of animals were sacrificed and histochemically examined at 2, 4 and 6 months after implantation. RESULTS: SEM of the BAM showed collagen fibers with many pores. VEGF receptor, FGF-1 receptor and neuregulin mRNA were expressed in the porcine BAM; BDNF mRNA was not detected. Two months after implantation, the graft sites exhibited excellent healing without contracture, and the fusion between the graft and the neighboring normal TA appeared to be well established. There were no significant histological differences between the implanted tunica and the normal control tunica at 6 months after implantation. CONCLUSION: The porcine BAM graft resulted in a structure which was sufficiently like that of the normal TA. This implantation might be considered applicable to the reconstruction of the TA in conditions such as trauma or Peyronie's disease.

Submucosal injection of poly(lactic-co-glycolic acid) microspheres in rabbit bladder as a potential treatment for urinary incontinence and vesicoureteral reflux: preliminary results.

Endoscopic injection of bulking agents has been gaining attention as a therapy for urinary incontinence and vesicoureteral reflux because this therapy is simpler, less operation time-consuming and less painful than traditional surgical operations. The ideal bulking agent for the injection therapies must be easily injectable, biocompatible, volume-stable, non-antigenic and non-migratory. We evaluated poly(lactic-co-glycolic acid) (PLGA) microspheres as an injectable bulking agent for urologic injection therapies. To determine whether PLGA microspheres meet the requirements of an ideal bulking agent, PLGA microspheres were injected into the submucosal sites of a rabbit bladder wall. The microspheres were easily injectable. Two and five weeks post-implantation, histological examinations indicated that host cells from the surrounding bladder tissues migrated to the space between the injected microspheres and formed new hybrid tissue structures. Lymphocyte migration was noted around the implanted microspheres, but the inflammatory reaction diminished at 5 weeks. The hybrid tissue volume did not significantly decrease over time. There was no evidence of microsphere migration to the distant organs. Although long-term studies are needed to evaluate the therapeutic potential of this method, these preliminary results suggest the possibility of PLGA microspheres as a potentially useful injection material for urinary injection therapies.

Nicotine induces apoptosis in TM3 mouse Leydig cells.

OBJECTIVE: To investigate whether nicotine-induced testicular toxicity involves the induction of apoptosis in Leydig cells. DESIGN: Cell study using cells of the TM3 cell line derived from mouse Leydig cells. SETTING: Academic research laboratory. INTERVENTION(S): Morphological and biochemical analyses for the detection of apoptosis. MAIN OUTCOME MEASURE(S): The effect of nicotine on the occurrence of apoptosis was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 4,6-diamidino-2-phenylindole staining, terminal deoxynuclotidyl transferase-mediated dUTP nick end labeling assay, DNA fragmentation assay, reverse transcription-polymerase chain reaction, caspase-3 enzyme assay, and Western blot analysis. Nicotine treatment exhibits several features of apoptosis in mouse Leydig cells. RESULT(S): TM3 cells treated with nicotine exhibit several features of apoptosis. It was also shown that nicotine increases the mRNA level of bax and decreases that of bcl-2. In addition, nicotine enhanced the expression of the activated form of caspase-3 and caspase-3 enzyme activity. CONCLUSION(S): Nicotine appears to activate specific intracellular death-related pathways, probably by bax-dependent activation of caspase-3, inducing apoptosis in Leydig cells. Thus, nicotine-induced apoptosis of Leydig cells might be one of the important mechanisms behind nicotine-related urogenital disorders in men.

Renal tissue reconstitution by the implantation of renal segments on biodegradable polymer scaffolds.

Renal units were created in vivo by transplanting isolated renal segments on three-dimensional, biodegradable polymer scaffolds. Renal segments, freshly isolated from rat kidneys, were seeded on polymer scaffolds and subcutaneously implanted in athymic mice for two and four weeks. Three-dimensional renal reconstructs were formed with glomeruli and tubules, showing a possibility of reconstituting renal structures by transplanting renal segments.

Alcohol induces apoptosis in TM3 mouse Leydig cells via bax-dependent caspase-3 activation.

To investigate whether ethanol induces apoptosis in Leydig cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, terminal deoxynuclotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, 4,6-diamidino-2-phenylindole (DAPI) staining, DNA fragmentation assay, caspase-3 enzyme assay, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were performed on TM3 mouse Leydig cells. Through morphological and biochemical analyses, it was demonstrated that TM3 cells treated with ethanol at concentrations of 50 and 100 mM exhibit classical apoptotic features. In addition, it was shown that ethanol induces increases in levels of bax and caspase-3 and a decrease in bcl-2 expression. Based on the results, alcohol appears to activate specific intracellular death-related pathways leading to bax-dependant caspase-3 activation and the induction of apoptosis in Leydig cells.