[Expressions of interleukin-17 and interleukin-8 in the prostatic tissue of the patients with BPH or BPH with inflammation].

OBJECTIVE: To investigate the expressions of interleukin-17 (IL-17) and interleukin-8 (IL-8) in benign prostatic hyperplasia (BPH) and BPH complicated with histological inflammation and their significance. METHODS: According to the results of HE staining, we divided 60 cases of BPH treated by transurethral resection of the prostate (TURP) into a BPH group (n = 23) and a BPH with inflammation group (n = 37). We analyzed the clinical data of the patients and determined the mRNA and protein expressions of IL-17 and IL-8 by immunohistochemistry, real-time fluorescence quantitative PCR, and Western blot, respectively. RESULTS: Compared with the BPH patients complicated with inflammation, the BPH group showed significantly lower International Prostate Symptom Score (IPSS) (29.1 ± 6.2 vs 21.6 ± 3.7), quality of life score (QoL) (5.4 ± 1.3 vs 4.4 ± 1.6), postvoid residual urine volume (RUV) (ï¼»198.6 ± 15.5ï¼½ vs ï¼»98.2 ± 19.3ï¼½ ml), prostate volume (ï¼»69.2 ± 24.1ï¼½ vs ï¼»49.8 ± 16.5ï¼½ ml), PSA level (ï¼»7.4 ± 1.9ï¼½ vs ï¼»2.8 ± 0.8ï¼½ µg/L) and serum c-reactive protein content (CRP) (ï¼»5.1±2.0ï¼½ vs ï¼»1.5±0.6ï¼½ mg/L), but a higher maximum urine flow rate (Qmax) (ï¼»4.7 ± 2.1ï¼½ vs ï¼»8.2 ± 1.8ï¼½ ml/s) (all P<0.05). The former group had a significantly higher incidence rate of urinary retention than the latter (32.4% ï¼»12/37ï¼½ vs 8.69% ï¼»2/23ï¼½), mRNA expressions of IL-17 (0.303 ± 0.076 vs 0.042 ± 0.019) and IL-8 (0.536 ± 0.059 vs 0.108 ± 0.025), and protein expressions of IL-17 (0.88 ± 0.10 vs 0.34 ± 0.05) and IL-8 (1.07 ± 0.08 vs 0.43 ± 0.04) (all P<0.05). CONCLUSIONS: The expressions of IL-17 and IL-8 are upregulated in the prostatic tissue of the BPH patients with inflammation, which may play a significant role in the development and progression of BPH.

The role of TSG-6 and uroplakin III in bladder pain syndrome/ interstitial cystitis in rats and humans.

OBJECTIVES: We investigated the relationship between the expression of tumor necrosis factor-inducible gene 6 (TSG-6) with inflammation and integrity of the bladder epithelium in the bladder tissues of patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and the mechanism of action using a rat model of BPS/IC. MATERIALS AND METHODS: Expression of TSG-6 and uroplakin III was determined by immuno- histochemistry of bladder biopsy samples from control human subjects and patients with verified BPS/IC. Our rat model of BPS/IC was employed to measure the perfusion of bladders with hyaluronidase, and assessment of the effect of TSG-6 administration on disease progression. Treatment effects were assessed by measurement of metabolic characteristics, RT-PCR of TGR-6 and interleukin-6, bladder histomorphology, and immunohistochemistry of TGR-6 and uroplakin III. RESULTS: The bladders of patients with BPS/IC had lower expression of uroplakin III and higher expression of TSG-6 than controls. Rats treated with hyaluronidase for 1 week developed the typical signs and symptoms of BPS/IC, and rats treated with hyaluronidase for 4 weeks had more serious disease. Administration of TSG-6 reversed the effects of hyaluronidase and protected against disease progression. CONCLUSION: Our results indicate that TSG-6 plays an important role in maintaining the integrity of the bladder epithelial barrier.

[Significance of nerve growth factor expression in the prostate tissue of spontaneously hypertensive rats].

OBJECTIVE: To investigate the changes of the expressions of the nerve growth factor (NGF) and its mRNA in the prostate tissues of spontaneously hypertensive rats (SHR) of different ages and their significance. METHODS: SHRs and normotensive Wistar Kyoto (WKY) rats were killed at 1 month (young), 6 months (adult) and 12 months (aging), respectively, 5 in each group. Their prostate indexes were calculated, and the expressions of NGF and its mRNA in the ventral prostate tissue were detected by immunohistochemistry and RT-PCR. RESULTS: The prostate indexes of the SHR and WKY groups were 1.16 +/- 0.06 and 1.03 +/- 0.09 at 1 month, 1.12 +/- 0.14 and 0.93 +/- 0.07 at 6 months, and 1.11 +/- 0.05 and 0.96 +/- 0.09 at 12 months, significantly higher in the former group than in the latter either at 6 or at 12 months (P < 0.05), but with no obvious difference at 1 month (P > 0.05). The expressions of NGF and its mRNA in the ventral prostate tissue were detected in all groups, and elevated gradually with the increase of age (P < 0.05). Among those of the same age, the expression levels were markedly higher in the SHR than in the WKY group (P < 0.05). CONCLUSION: In SHRs with benign prostate hyperplasia (BPH), the enhanced excitation of the sympathetic nervous system may be a common mechanism underlying BPH and hypertension, and NGF plays an important role in it.

[Expression of COX-2 and VEGF and their correlation with angiogenesis in human clear cell renal cell carcinoma].

OBJECTIVE: To investigate the expression of COX-2 and VEGF in clear cell renal cell carcinoma (CCRCC) and their correlation with tumor angiogenesis. METHODS: Envision immunohistochemistry was used to determine the expression of COX-2 and VEGF, and microvessel density (MVD) was marked by CD34 in 80 CCRCC tissues and 20 normal kidney tissues. The relationship between the above mentioned markers were analyzed. RESULTS: Expressions of COX-2 and VEGF were noted in both CCRCC and normal kidney tissues. The positive rates of COX-2 and VEGF were significantly higher in CCRCC than in normal kidney (P < 0.05); The expression of COX-2 was correlated with TNM stage (P < 0.05), histological grade (P < 0.05) and lymph node metastasis (P < 0.05) in CCRCC, but not with age (P = 0.663) and diameter of tumor (P = 0.528). Both COX-2 expression (r = 0.851, P < 0.01) and VEGF expression (r = 0.736, P < 0.01) were significantly associated with MVD in CCRCC. There was a positive correlation between expression of cox-2 and that of VEGF in CCRCC. CONCLUSION: COX-2 expression is correlated with tumor angiogenesis in CCRCC. It is likely that VEGF is one of the most important mediators in the COX-2 angiogenic pathway.

Gene transfer into porcine myocardium via pericardial cavity by homemade easy puncture device.

OBJECTIVE: To explore the feasibility and safety of gene transfer into porcine myocardium via the pericardial cavity by a homemade easy device. METHODS: Replication-deficient recombinant adenoviral vector carrying LacZ report gene (Ad-LacZ) was constructed by the calcium phosphate precipitation method. Twelve healthy Chinese mini-swine were randomly divided into experimental group (n = 6) and control group (n = 6). Acute myocardial infarction (AMI) model was established by balloon occlusion of the distal part of D1 branch of left anterior descending (LAD) artery, at the same time the intrapericardial cavity injections were performed through the small incision of the abdominal wall below the xyphoid appendix using a homemade device. Then gene transfer was performed using a central venous catheter. The pericardium was pretreated with injection of a mixture of collagenase (1,200 U) and hyaluronidase (3,000 U) in both groups. Then 2.0 x 10(9) plaque formation unit (PFU) Ad-LacZ was injected into the pericardial cavity in experimental group, while 1 mL of normal saline was injected in the control group. The beta-galactosidase activity detection and X-gal staining of the ischemic myocardium were performed on the 3rd, 7th, and 28th day after injection. RESULTS: The LAD artery was occluded completely and infarction and ischemia were detected by histological assessment In experimental group, the X-gal staining positive cells and beta-galactosidase activity quantification were detectable on the 3rd day after injection, increased markedly on the 7th day, and then declined on the 28th day. The transfer efficiencies indicated by the positive myocardial cells were 16.7%, 45.6% , 22.8% on the 3rd, 7th, 28th day, respectively. In control group, no positive cells and beta-galactosidase activity were observed. CONCLUSION: Adenovirus can be transferred into ischemic myocardium and express target gene in the AMI model for four weeks with the homemade easy device via pericardial cavity pretreated by collagenase and hyaluronidase.

[Effects of atorvastatin on the function of dendritic cells in patients with unstable angina pectoris].

OBJECTIVE: To investigate the function of dendritic cells (DC) in patients with unstable angina pectoris (UAP) and the effects of atorvastatin on it. METHODS: 27 patients with UAP were divided into two groups treated respectively with regular pharmacotherapy and regular pharmacotherapy plus atorvastatin. PBMC from the UAP patients (before and 2 weeks after the treatment) and 11 healthy subjects were incubated and induced to mature DC in a completed medium containing GM-CSF and IL-4. Flow cytometric analysis was used to detect the expression of co-stimulating factor CD86 (B7-2) on DC. The stimulating capacity of DC was determined in allogenic mixed lymphocyte reaction (MLR). ELISA was used to analyze the level of cytokines (IL-1beta, IL-6, IL-10 and TNF-alpha) in the medium of MLR. Relationship of expression of CD86 to risk factors and blood CRP level was also analyzed. RESULTS: When compared with normal group, CD86 on DC was much more expressed in UAP patients; the stimulating capacity of DC in MLR was higher; T lymphocytes in MLR secreted higher levels of pro-inflammation cytokines (IL-1beta, IL-6 and TNF-alpha) and lower level of anti-inflammation cytokine (IL-10). Blood LDL-C before treatment was positively related to the expression of CD86. Atorvastatin inhibited the function of DC and lowered blood level of CRP and CD86, the levels of which were significantly positively correlated. CONCLUSIONS: DC in UAP are activated, which may play an important role in initiating immune reaction in the plaque. LDL-C may be one of the activators of DC; inhibitory effect of atorvastatin on inflammation in UAP may be due to its inhibition on DC.

Inhibition of NOS2 ameliorates cardiac remodeling, improves heart function after myocardial infarction in rats.

OBJECTIVE: Previous studies have shown increased expression of nitric oxide synthase 2 (NOS2) in rat heart several weeks after myocardial infarction (MI). The aim of this study was to examine the effect of chronic administration of S-methylisothiourea (SMT), a selective NOS2 inhibitor, commenced one week after MI on hemodynamic parameters and left ventricular (LV) remodeling in rats. METHODS: Rats with MI induced by left coronary ligation were given SMT (0.5 mg/kg/d) or saline by gavage starting one week after MI. After chronic administration for five weeks, hemodynamic and cardiac morphologic studies were performed, and lung water content, plasma NO(x) concentration, NOS2 protein level, myocyte size and collagen volume fraction of noninfarct LV area were quantified. RESULTS: The NO(x) concentration in plasma and the NOS2 protein level in noninfarct myocardium in MI rats were higher than controls. When compared with the MI rats receiving saline, chronic administration of SMT reduced myocyte size (15.1 +/- 1.6 microm vs 16.9 +/- 2.3 microm, P < 0.05), collagen volume fraction of noninfarct LV area (4.4% +/- 1.1% vs 5.7% +/- 1.2%, P < 0.01) and lung water content (77.4% +/- 1.4% vs 79.3% +/- 0.9%, P < 0.01), without affecting infarct size. Administration of SMT had no significant effect on heart rate and mean arterial pressure, but decreased LV end-diastolic pressure (8.7 +/- 2.1 mmHg vs 13.4 +/- 3.1 mmHg, P < 0.01), central venous pressure (0.9 +/- 0.3 mmHg vs 1.5 +/- 0.5 mmHg, P < 0.01) and inner LV diameter (6.9 +/- 0.3 mm vs 7.2 +/- 0.3 mm, P < 0.05) in the MI rats. Plasma level of NO(x) in the MI rats receiving SMT was reduced to control level. CONCLUSIONS: Chronic administration of SMT had beneficial effects on LV remodeling and cardiac dysfunction in MI rats, suggesting the possibility that inhibition of NOS2 could be a therapeutic tool for cardiac dysfunction after MI.

Prevention of myosin-induced autoimmune myocarditis in mice by anti-L3T4 monoclonal antibody.

This study was aimed at studying the effect of the induction of immune tolerance to swine cardiac myosin from anti-L3T4 monoclonal antibody injection and whether the immune tolerance could protect mice with myosin-induced myocarditis from myocardial injury. Twenty-four Balb/c mice were divided into two groups at random. All of the mice were immunized with swine cardiac myosin on the 1st day, 14th, 28th, 42nd, and 52nd day. Immune tolerance was induced by triplicate injections of 400 microg anti-L3T4 McAb on the 0 day (intravenous), 1st day, and 2nd day (intraperitoneal) in McAb-treated group. In the saline-treated group, saline of the same volume as anti-L3T4 monoclonal antibody was used as a control. The sera and hearts biopsies of all mice were collected on the 58th day. The anti-cardiac myosin antibody was examined with ELISA, and pathological changes of heart were observed by light microscope. It was shown that mice immunized with swine cardiac myosin could produce anti-myosin antibody and the anti-cardiac myosin antibody was positive in most of the saline-treated group but negative in the McAb-treated group. Morphologically, myocardial degeneration, necrosis, and infiltration of inflammatory cells were found in the saline-treated group but not in the McAb-treated group. In conclusion, this study indicated that the immune tolerance to cardiac myosin was induced by the anti-L3T4 monoclonal antibody, and accordingly myocardial injury could be prevented by induction of immune tolerance.