Nerve growth factor and substance P: expression in a rat model of diabetic bladder.

OBJECTIVE: To evaluate the gene and protein expression of nerve growth factor (NGF) and substance P (SP) in the bladder 8 weeks after diabetes induction and investigate the pathogenesis of diabetic cystopathy. METHODS: Thirty Wistar rats were divided into three groups: control (n = 10), streptozotocin-induced diabetic group (n = 10) and Pygeum africanum (P. africanum) group (n = 10; diabetic rats were given P. africanum (100 mg/kg/day)). Eight weeks later, the bladders were dissected. We measured the expression of NGF and SP in the bladders using RT-PCR, ELISA and immunohistochemistry. RESULTS: We found a significantly reduced expression of NGF in the bladders from the diabetic group compared with the control. Immunohistochemical studies showed a statistically significant reduction of SP in the bladders from the diabetic group compared with the control (P < 0.05). Expression of NGF was greatly increased in the P. africanum group compared with that of the diabetic group. Immunohistochemical studies showed an increased level of SP in the bladders from the P. africanum group compared with the control (P < 0.05). CONCLUSIONS: Our findings indicated that the decrease in NGF and SP may be a contributory factor in diabetic cystopathy. In addition, P. africanum could significantly upregulate the expression of NGF and SP in diabetic rats.

Pygeum africanum: effect on oxidative stress in early diabetes-induced bladder.

OBJECTIVE: To evaluate the effect of Pygeum africanum on oxidative stress and functional changes of the bladder after diabetes induction. MATERIALS AND METHODS: Thirty-two adult Wistar male rats were treated daily for 8 weeks and grouped as follows: Control group (n = 6), Streptozotocin-induced diabetic group (n = 10), diabetes plus P. africanum group (n = 10), and control plus P. africanum group (n = 6). After diabetes induction for 4 weeks, the diabetes plus P. africanum and control plus P. africanum groups were fed with P. africanum (100 mg/kg, orally) in peanut oil for another 4 weeks. The catalase, superoxide dismutase activity, and malondialdehyde levels were measured as a marker of lipid peroxidation. The levels of inducible nitric oxide synthase were also evaluated. Urodynamic studies were performed to evaluate the functional changes of diabetic bladders after P. africanum treatment. RESULTS: The catalase and superoxide dismutase activities significantly increased (P < 0.05) and maleic dialdehyde levels significantly decreased from diabetic plus P. africanum group compared with diabetic group (P < 0.05). Immunohistochemical studies showed a significantly decreased number of inducible nitric oxide synthase-positive cells in diabetic plus P. africanum group compared with diabetic group (P < 0.05). In diabetic plus P. africanum group, maximal bladder volume significantly decreased, while bladder pressure and maximal bladder pressure significantly increased compared with diabetic group (P < 0.05). CONCLUSIONS: Early treatment with P. africanum could effectively suppress the oxidative stress status in diabetic bladder and may slow down the process of diabetic cystopathy.

Alterations of urine TGF-beta1 and bFGF following bladder outlet obstruction: a predictor for detrusor contractibility?

OBJECTIVES: To investigate the alterations of urine transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) following bladder outlet obstruction (BOO) in rats and to determine their correlation with the impaired detrusor contractibility. METHODS: Wistar rats were divided into control, 2-week BOO 6-week and BOO groups. Impaired detrusor contractibility was quantified by measuring detrusor contraction force (DCF) of detrusor strip stimulated by carbachol. The enzyme-linked immunosorbent assay method was used to determine the urine levels of the 2 factors. Correlation analysis was conducted between DCF and urine levels of the 2 factors to see if there was an association between them after BOO. RESULTS: DCF was found to be significantly lower in the 6-week BOO group than in the 2-week BOO and control groups. There is no significant difference regarding urine TGF-beta1 between the 2-week BOO and control groups (p > 0.05). Urine TGF-beta1 level in the 6-week BOO group was significantly higher than in the 2-week BOO (p < 0.05) and control groups (p < 0.05). There existed a negative correlation between DCF and urine TGF-beta1 (p < 0.05). CONCLUSIONS: In an animal model, our results have suggested the potential role of urine TGF-beta1 as a noninvasive biomarker to predict detrusor contractibility after BOO.

E-cadherin tissue expression and urinary soluble forms of E-cadherin in patients with bladder transitional cell carcinoma.

OBJECTIVE: To investigate the clinical significance of E-cadherin (E-CD) expression in human bladder transitional cell carcinoma (TCC) tissue and soluble forms of E-cadherin (sE-CD) in the urine of patients with TCC. MATERIALS AND METHODS: One hundred and two specimens of bladder TCC and 10 normal bladder tissues were stained immunohistochemically with anti-E-CD monoclonal antibody. The urinary sE-CD from 59 subjects with TCC or controls was measured with enzyme-linked immunosorbent assay (ELISA). All results were analyzed statistically between groups. RESULTS: The expression of E-CD in bladder TCC correlated well with grade and stage but had no significant correlation with the size or number of the tumors. Normal expression rate of E-CD is significantly higher in primary than in recurrent tumors. The level of urinary sE-CD was higher in patients with TCC than in normal controls or patients with benign disorders of the urinary system. Urinary sE-CD levels were strongly correlated with tumor grade but showed no significant correlation with the stage, size and number of the tumors. The urinary sE-CD level is significantly higher in the recurrent group than in the primary group. CONCLUSIONS: Expression of E-CD in the tissue of TCC and the urinary level of sE-CD are very closely associated with the biological behaviors of bladder TCC.

Expression of transforming growth factor beta1 gene, basic fibroblast growth factor gene and hydroxyproline in diabetes-induced bladder dysfunction in a rat model.

AIMS: To investigate the content of hydroxyproline (Hyp) and the expression of transforming growth factor beta1 (TGF beta1) and basic fibroblast growth factor (bFGF) in the bladder 8 weeks after diabetes induction. METHODS: Thirty wistar rats were divided into three groups: control (n = 10), streptozotocin-induced diabetic group (n = 10), TAD group (n = 10; diabetic rats were fed with Tadenan 100 mg kg(-1) day(-1)). Eight weeks later, the bladders were dissected. RT-PCR, immunohistochemistry, and ELISA were used to detect the expression of TGF beta1 and bFGF in the bladder. Also hydroxyproline (Hyp) was measured using a method based on alkaline hydrolysis. RESULTS: The content of hydroxyproline in the diabetic group was greater than that of control group (P < 0.05); we found significantly increased expression of TGF beta1 mRNA and bFGF mRNA in the bladder from the diabetic group compared with the control group; immunohistochemical and ELISA studies showed a statistically significant increased expression of TGF beta1 protein and bFGF protein in the bladder from the diabetic group compared with the control group (P < 0.05). The content of hydroxyproline in TAD group was less than that of diabetic group (P < 0.05); mRNA expression of TGF beta1 and bFGF greatly decreased in TAD group compared with that of the diabetic group; immunohistochemical and ELISA studies showed decreased levels of TGF beta1 protein and bFGF protein in the bladder from TAD group compared with the diabetic group (P < 0.05). CONCLUSIONS: Rats with streptozoticin-induced diabetes mellitus showed significant increase in hydroxyproline, TGF beta1 and bFGF levels in their bladders, which may be an important mechanism inducing diabetic cystopathy. Tadenan could effectively reduce hydroxyproline, TGF beta1, and bFGF levels.