The relationship between androgens, regulators of collagen metabolism, and Peyronie's disease: a case control study.

INTRODUCTION: Changes in collagen metabolism have been postulated to play a pivotal role in the pathogenesis of Peyronie's Disease (PD). Androgens such as dehydroepiandrosterone sulfate (DHEA-S) and testosterone influence collagen metabolism by modulating the activity of matrix metalloproteases (MMP) and tissue inhibitors of metalloproteases (TIMP). AIM: The aim of this study was to evaluate the interrelationship between androgens (DHEA-S and testosterone), key regulators of collagen metabolism such as insulin-like growth factor (IGF) 1 and IGF Binding Protein 3 (IGF-BP3), the MMP/TIMP system, and PD. METHODS: Age matched PD patients (14) and healthy men (10) who acted as controls were recruited. Blood samples were collected from all subjects in the early morning hours after an overnight fast. MAIN OUTCOME MEASURES: Serum levels of testosterone, sex hormone binding globulin, DHEA-S, 3-α-androstanediol glucuronide, pro-MMP-1, MMP-1, MMP-2, TIMP-1, TIMP-2, IGF-1 and IGF-BP3 were measured in both groups. Statistical methods included univariate, bivariate, and multivariate regression models. RESULTS: Levels of DHEA-S (114.5 vs. 169.5 µg/dL; p = 0.03), IGF-BP3 (2.96 vs. 3.79 µg/mL; p = 0.01), and TIMP-1 (173.1 vs. 195 ng/mL; p = 0.01) were significantly lower in PD patients. In contrast, the level of TIMP-2 (102 vs. 85 ng/mL; p = 0.001) was significantly lower in the control group. Using stepwise regression analysis, only TIMP-2 (p < 0.001) and DHEA-S (p = 0.04) were significantly related to PD in the final model (R(2) = 0.63). TIMP-1 and DHEA-S (r = 0.55, p < 0.05) were positively correlated in the PD group, whereas IGF-1 and testosterone (r = -0.54, p < 0.05), and IGF-BP3 and testosterone (r = -0.68, p < 0.05) were negatively correlated in PD patients. CONCLUSIONS: Our findings suggest that decreased levels of adrenal androgens may be implicated in the pathogenesis of PD. The mechanism and clinical relevance of this observation remain to be established.

The effect of alpha-blocker treatment on bladder hypoxia inducible factor-1 alpha regulation during lower urinary tract obstruction.

AIMS: To determine whether alpha1-blocker treatment, in chronic bladder outlet obstruction (BOO), influences bladder tissue ischemia. MATERIALS AND METHODS: This prospective study included 60 patients with BOO, of which 40 were under alpha1-blocker medication and 20 without treatment. Patients underwent transurethral resection of the prostate (TURP) or suprapubic prostatectomy (SPP). Ten patients with non-muscle invasive bladder cancer underwent transurethral resection of the bladder tumor and served as the control group. Tissue specimens were immunohistochemically stained for hypoxia inducible factor-1alpha (HIF-1alpha). RESULTS: Bladder tissue from obstructed subjects showed high immunoreactivity to HIF-1alpha. The specimens from the control group, showed no or weak, mainly cytoplasmic immunoreactivity to HIF-1alpha. Patients under alpha -blocker treatment did not differ in the number of HIF-1alpha positive cells compared to subjects with no treatment (median number 86.8 [20-150] and 88.6 [0-175], respectively) (p > 0.05). The lowest bladder pressure at which HIF-1alpha was up regulated, was detected at detrusor pressure Qmax (PdetQmax) = 60 cm H2O. CONCLUSIONS: Treatment with alpha-blockers in obstructed patients considered as non-responders, does not result in HIF-1alpha down regulation, thus bladder continues to be under chronic stress.

The effect of alpha-blocker treatment on bladder hypoxia inducible factor-1 alpha regulation during lower urinary tract obstruction

AIMS: To determine whether á1-blocker treatment, in chronic bladder outlet obstruction (BOO), influences bladder tissue ischemia. Materials and methods: This prospective study included 60 patients with BOO, of which 40 were under á1-blocker medication and 20 without treatment. Patients underwent transurethral resection of the prostate (TURP) or suprapubic prostatectomy (SPP). Ten patients with non-muscle invasive bladder cancer underwent transurethral resection of the bladder tumor and served as the control group. Tissue specimens were immunohistochemically stained for hypoxia inducible factor-1á (HIF-1á). Results: Bladder tissue from obstructed subjects showed high immunoreactivity to HIF-1á. The specimens from the control group, showed no or weak, mainly cytoplasmic immunoreactivity to HIF-1á. Patients under á -blocker treatment did not differ in the number of HIF-1á positive cells compared to subjects with no treatment (median number 86.8 [20-150] and 88.6 [0-175], respectively) (p > 0.05). The lowest bladder pressure at which HIF-1á was up regulated, was detected at detrusor pressure Qmax (PdetQmax) = 60 cm H2O. Conclusions: Treatment with á-blockers in obstructed patients considered as non-responders, does not result in HIF-1á down regulation, thus bladder continues to be under chronic stress.

Synchronous chromophobe and papillary renal cell carcinoma. First report and review of the pathogenesis theories.

The coexistence of different subtypes of renal cell carcinoma (RCC) within a single kidney is an extremely unusual entity. Presented herein is the case of a 57-year-old man with two RCC of chromophobe and papillary histology. Very few reports in the literature describe double or triple synchronous renal neoplasms. To our knowledge this is the first report of this RCC subtype combination, which might trigger further investigation on the RCC pathogenesis theories.

Immunohistochemical estimation of hypoxia in human obstructed bladder and correlation with clinical variables.

OBJECTIVE: To investigate the tissue distribution of ischaemia in human detrusor in patients with bladder outlet obstruction (BOO) and to correlate the results with clinical variables, as clinical BOO is a common problem in ageing men and ischaemia might be important in detrusor dysfunction. PATIENTS AND METHODS: From September 2004 to October 2006, 70 patients were recruited, comprising 60 scheduled for surgery to treat benign prostatic hyperplasia (the study group) and 10 as controls. Detrusor tissue was retrieved and stained for hypoxia-inducible factor (HIF)-1alpha, a cellular marker of hypoxia. RESULTS: The mean (sd) total number of cells immunoreactive to HIF-1alpha in the study group was 93.3 (48.09), and in the specimens from the control group only few rare cells showed weak immunoreactivity to HIF-1alpha (0-2). Positive cells were in different proportions between muscle bundles and submucosa, expressed mainly in stromal cells. The urothelium and detrusor muscle showed no immunoreactivity to HIF-1alpha. There was strong immunoreactivity in patients with prolonged BOO (<10 years), declining thereafter, and in those patients with urinary retention. CONCLUSIONS: The urothelium and detrusor seem to be more resistant to hypoxic stress, while stromal cells perceive low oxygen tension. The bladder response to chronic hypoxia through HIF-1alpha expression is limited in time and might depend on the functional status of the detrusor.

Androgens and bladder outlet obstruction: a correlation with pressure-flow variables in a preliminary study.

OBJECTIVES: To determine the relationship between androgens, lower urinary tract symptoms (LUTS) and urodynamic variables of bladder outlet obstruction (BOO) in patients with LUTS/benign prostatic hyperplasia (BPH), as androgens are important in the pathogenesis of LUTS. PATIENTS AND METHODS: Twenty-five men with symptomatic BPH were enrolled in the study and had a complete urodynamic investigation, establishing BOO. Age, prostate-specific antigen level, prostate volume and postvoid residual volume were recorded and the International Prostate Symptom Score (IPSS) was estimated. Detrusor pressure at maximum flow (P(det)Q(max)), at urethral closure (P(det)Cl, the pressure at the end of urinary flow) and maximum detrusor pressure (P(detmax)) was recorded, while detrusor overactivity (DO) was noted when present. Blood samples were collected to measure total testosterone (T), and free T (FT) was calculated. Patients were grouped according to FT levels as low (<72 pg/mL) and normal (FT > or =72 pg/mL). RESULTS: Ten patients had a low FT level, with a mean (sd) of 54.3 (16.5) pg/mL, and 15 a normal level of FT, of 90.5 (11) pg/mL. FT was negatively correlated with P(det)Cl, and P(det)Q(max); the mean P(det)Cl and P(det)Q(max) differed significantly between patients with low and normal FT levels. Fourteen patients had DO and they had significantly lower levels of FT than those with no DO. All patients with a FT level of <60 pg/mL had DO, and the presence of instability differed significantly from the rest of the group. CONCLUSIONS: Low T levels in clinical BOO correlated negatively with P(det)Cl and P(det)Q(max), while promoting DO. Androgen seems to have an ameliorating role in lower urinary tract function.