Zhaocun Zhang

Grape Seed Proanthocyanidin Extract Ameliorates Diabetic Bladder Dysfunction via the Activation of the Nrf2 Pathway.

Diabetes Mellitus (DM)-induced bladder dysfunction is predominantly due to the long-term oxidative stress caused by hyperglycemia. Grape seed proanthocyanidin extract (GSPE) has been reported to possess a broad spectrum of pharmacological and therapeutic properties against oxidative stress. However, its protective effects against diabetic bladder dysfunction have not been clarified. This study focuses on the effects of GSPE on bladder dysfunction in diabetic rats induced by streptozotocin. After 8 weeks of GSPE administration, the bladder function of the diabetic rats was improved significantly, as indicated by both urodynamics analysis and histopathological manifestation. Moreover, the disordered activities of antioxidant enzymes (SOD and GSH-Px) and abnormal oxidative stress levels were partly reversed by treatment with GSPE. Furthermore, the level of apoptosis in the bladder caused by DM was decreased following the administration of GSPE according to the Terminal Deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) assay. Additionally, GSPE affected the expression of apoptosis-related proteins such as Bax, Bcl-2 and cleaved caspase-3. Furthermore, GSPE showed neuroprotective effects on the bladder of diabetic rats, as shown by the increased expression of nerve growth factor (NGF) and decreased expression of the precursor of nerve growth factor (proNGF). GSPE also activated nuclear erythroid2-related factor2 (Nrf2), which is a key antioxidative transcription factor, with the concomitant elevation of downstream hemeoxygenase-1 (HO-1). These findings suggested that GSPE could ameliorate diabetic bladder dysfunction and decrease the apoptosis of the bladder in diabetic rats, a finding that may be associated with its antioxidant activity and ability to activate the Nrf2 defense pathway.

Cannabinoid receptors 1 and 2 are associated with bladder dysfunction in an experimental diabetic rat model

To investigate diabetes‐associated changes in urinary bladder expression of cannabinoid receptors 1 and 2 (CB1 and CB2) and the functional role of CB agonists and antagonists in mediating phasic contractions of isolated bladder strips using a streptozotocin‐induced diabetic rat model.

Long‐term outcome following thulium vaporesection of the prostate

The continuous wave 2‐μm Thulium Laser has been introduced as potential technology with both high efficiency and safe practice; although little data have been shown regarding the long‐term outcomes.

Changes in alpha1-adrenoceptor and NGF/proNGF pathway: a possible mechanism in diabetic urethral dysfunction.

Objective: To investigate the changes in the α1-adrenoceptor and nerve growth factor (NGF)/NGF precursor (proNGF) pathway in the urethra after diabetes induction. Materials and Methods: Urethral relaxation function was determined by simultaneous recordings of intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) in diabetic rats. The expression of α1-adrenoceptor, NGF, proNGF, low-affinity p75 receptor for neurotrophins (p75NTR) and sortilin in the urethras was measured using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay and Western blotting. Results: In diabetic rats, the lowest urethral pressure (UPP nadir) during urethral relaxation was significantly higher. Intravenous administration of tamsulosin, an α1-adrenoceptor antagonist, significantly decreased the UPP nadir and baseline UPP in diabetic rats. RT-qPCR and Western blotting studies showed a statistically significant increase of α1a- and α1b-adrenoceptor in the urethras from the diabetic group (p < 0.05). The expression of NGF was significantly decreased in the urethras from the diabetic group while the expression of proNGF was significantly increased (p < 0.05). The p75NTR level in the urethras of diabetic rats was decreased compared with controls (p < 0.05) and there was no significant difference regarding sortilin between the two groups (p > 0.05). Conclusion: This study validated the diabetic urethral dysfunction and furthermore indicated that the increase in the expression of α1-adrenoceptor and changes in the NGF/proNGF pathway may be involved in diabetic urethral dysfunction.

Clinical characteristics and pathology of thyroid‑like follicular carcinoma of the kidney: Report of 3 cases and a literature review

Thyroid-like follicular carcinoma (TLFC) of the kidney is an extremely rare type of renal tumor, which has not been classified under a known subtype of renal cell carcinoma. It is histologically similar to the primary thyroid follicular carcinoma; however, the characteristics lack thyroid immunohistochemical markers. The aim of the present study was to illustrate the clinical characteristics of 3 new cases along with a review of the literature. The patients were compared with regards to gender, age, location and size of the tumor, imageology, morphology, immunohistochemistry and prognosis. According to the limited data, TLFC occurs mainly in young women and its clinical manifestations have no difference with other renal tumors. Its imageological features resemble a large spectrum of benign and malignant renal and extra-renal conditions, which should be eliminated in the diagnostic process. Confirmed diagnosis depends on the examination of pathology and immunohistochemistry. Surgical ablation is the preferred therapeutic method. Currently, TLFC has a relatively good prognosis; however, this conclusion requires further cases and long-term follow-ups. Improving the understanding of TLFC can help avoid misdiagnosis and prevent inappropriate treatment.

Primary Adenocarcinoma of the Ureter with Elevated CarbohydrateAntigen-19-9: A Case Report and Review of the Literature

Primary adenocarcinoma of the upper tract urothelial cell carcinomas (UTUCs) is rarely reported. We report a case of primary adenocarcinoma of the ureter with elevated carbohydrate antigen 19-9 (CA-19-9). A 44-year-old male was admitted to the hospital for severe right flank and hypogastrium pain for 7 days without visible or microscopic haematuria. The patient underwent radical nephroureterectomy followed by chemotherapy with gemcitabine/ carboplatin and inorelbine/Adriamycin (ADM)/5-fluoro-2,4 (1 h, 3 h) pyrimidinedione (5-FU) and radiotherapy, and the level of CA19-9 decreased to normal. Histopathology revealed adenocarcinoma. The patient died of tumor pelvic metastasis after 6 months. A review of the literature is also reported.

AB049. Prognostic scores based on the preoperative plasma fibrinogen and serum albumin level as a prognostic factor in patients with upper urinary tract urothelial carcinoma

Background To clarify the prognostic value of preoperative plasma fibrinogen and serum albumin level, as known as FA score, in a cohort of Chinese patients with upper urinary tract urothelial carcinoma (UTUC). Methods The FA score was calculated based on optimal cutoff values of 3.53 g/L for fibrinogen and 43.56 g/L for albumin. Overall survival (OS) and cancer specific survival (CSS) was assessed using the Kaplan-Meier method and the equivalences of the survival curves were tested by log-rank tests. Results In univariate analysis, Tumor size, tumor grade, T stage and preoperative FA score were significantly associated with OS and CSS, and multivariate Cox proportional hazards regression analysis identified FA score was an independent predictor for OS and CSS. Conclusions The evaluation of preoperative FA score can be regarded as an independent prognostic factor for predicting OS and CSS of patients with UTUC. The fibrinogen and albumin levels are low cost, routine measured and easy accessibility in clinical practice.

Grape seed proanthocyanidin extract alleviates urethral dysfunction in diabetic rats through modulating the NO‑cGMP pathway

Oxidative stress is closely associated with the onset of diabetes mellitus (DM). Diabetic urethropathy is one of the most common complications of DM, but few studies have been conducted to investigate the role of oxidative stress in diabetic urethropathy. Grape seed proanthocyanidin extract (GSPE) has been previously reported to reduce oxidative injury. The present study aimed to investigate the role of oxidative stress and the protective effects of GSPE on urethral dysfunction using a streptozotocin-induced DM rat model. Female Wistar rats were divided into a control group (n=36), a DM group (n=36) and a DM + GSPE group (n=36). Urodynamic testing was performed using a PowerLab data acquisition device. The expression of neuronal nitric oxide synthase (nNOS), 3-nitrotyrosine and nuclear factor erythroid 2-related factor 2 (Nrf2) was determined using western blot analysis. The expression of 3-nitrotyrosine was also determined using immunohistochemistry. Nitric oxide (NO), cyclic guanosine monophosphate (cGMP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured using commercial ELISA kits. A significant increase was observed in the intravesical pressure thresholds for inducing urethral relaxation and the urethral perfusion pressure nadir in DM rats compared with the control group. GSPE was observed to reverse the increase of these parameters compared with the DM group. In addition, GSPE could reverse the downregulation of nNOS, NO and cGMP expression, and the decreased activities of antioxidant enzymes (SOD and GSH-Px). GSPE reversed the upregulation of 3-nitrotyrosine and MDA in DM rats. GSPE also activated Nrf2, which is a key antioxidative transcription factor. The findings of the present study demonstrated that GSPE protects urethra function in DM rats through modulating the NO-cGMP signaling pathway. The protective roles of GSPE may be associated with activation of the Nrf2 defense pathway.

AB260. Role of µ, κ, and δ opioid receptors in tibial inhibition of bladder overactivity in cats

Background To study the impact of µ, κ, and δ opioid receptors on tibial inhibition of bladder overactivity in cats Methods In α-chloralose anesthetized cats we examined the role of opioid receptor (OR) subtypes (µ, κ, and δ) intibialnerve stimulation (TNS) induced inhibition of bladder overactivity elicited by intravesical infusion of 0.25% acetic acid (AA). The sensitivity of TNS inhibition to cumulative intravenous doses of selective OR antagonists (cyprodime for µ, nor-binaltorphimine for κ, or naltrindole for δ ORs) was tested. Results Naloxone (1 mg/kg, i.v., an antagonist for µ, κ, and δ ORs) was administered at the end of each experiment. AA caused bladder overactivity and significantly (P<0.01) reduced bladder capacity to 21.1±2.6% of the saline control. TNS at 2 or 4 times threshold (T) intensity for inducing toe movement significantly (P<0.01) restored bladder capacity to 52.9±3.6% or 57.4±4.6% of control, respectively. Cyprodime (0.3–1.0 mg/kg) completely removed TNS inhibition without changing AA control capacity. Nor-binaltorphimine (3–10 mg/kg) also completely reversed TNS inhibition and significantly (P<0.05) increased AA control capacity. Naltrindole(1–10 mg/kg) reduced (P<0.05) TNS inhibition but significantly (P<0.05) increased AA control capacity. Naloxone (1 mg/kg) had no effect in cyprodime pre-treated cats, but reversed the nor-binaltorphimine induced increase in bladder capacity and eliminated the TNS inhibition remaining in naltrindole pre-treated cats. Conclusions These results indicate a major role of µ and κ ORs in TNS inhibition while δORs play a minor role. Meanwhile, κ and δORs also have an excitatory role in irritation-induced bladder overactivity.