[Correlation of high-risk HPV 16/18 infections with prostate cancer].

OBJECTIVE: To study the correlation of high-risk human papillomavirus 16 and 18 (HPV16/18) infections with the risk of prostate cancer (PCa) and their association with the clinicopathologic indexes of PCa. METHODS: We collected tissue samples from 75 cases of PCa and 73 cases of benign prostatic hyperplasia (BPH). We detected HPV16/18 infections in the samples by immunohistochemistry and PCR combined with reverse dot blot (RDB) assay. RESULTS: Immunohistochemistry revealed 16 cases of HPV16/18 positive in the PCa (21.3%) and 7 cases in the BPH samples (9.5%), with statistically significant difference between the two groups (P=0.049). PCR combined with RDB assay showed 17 cases of HPV16 infection (22.6%) and 13 cases of HPV18 infection (17.8%), including 4 cases of HPV16/18 positive, in the PCa group, remarkably higher than 6 cases of HPV16 infection (8.2%), 3 cases of HPV18 infection (4.1%) and no HPV16/18 positive in the BPH controls (P=0.001). No significant differences were observed between the result of immunohistochemistry and that of PCR combined with RDB assay (P=0.069). The risk of HPV16/18 infections was found to be correlated with the clinical T-stage and Gleason score of PCa (P<0.05 ) but not with the patient's age, PSA level or lymph node metastasis (P>0.05 ). CONCLUSIONS: High-risk HPV16/18 infections are correlated with the risk of prostate cancer.

Long-term ketamine abuse induces cystitis in rats by impairing the bladder epithelial barrier.

Long-term ketamine abuse is known to affect the lower urinary tract and produce symptoms of cystitis. However, the pathophysiology and causative mechanism of the changes in bladder function remain unclear. The present study aimed to investigate the existence of ketamine-induced cystitis in a rat model and characterize the underlining mechanisms. Rats were assigned to blank control, normal saline (NS), low-dose ketamine (LK, 5 mg/kg), and high-dose ketamine (HK, 50 mg/kg) groups. The two experimental groups received ketamine hydrochloride daily for 16 weeks. All rats were housed individually for assessment of urinary frequency and urine volume. Urinary biomarkers were measured at different time points. Rat bladders were excised for histopathology, immunohistochemistry, and western blot analysis. Ketamine-treated rats had increased urinary frequency compared to NS-treated rats at Week 16. Urinary nitric oxide and antiproliferative factor levels were increased in ketamine-treated rats within the first 30 h after administration. After long-term ketamine administration, urinary glycoprotein GP51 and potassium levels were decreased in the HK and LK groups compared to the NS group. Ketamine-treated rats showed thickened bladder epithelial layer, increased expression of inducible nitric oxide synthase and occludin, and decreased expression of zonula occludens-1 in the bladder wall. Ketamine, or its urinary metabolites, disrupted the proliferation of bladder epithelial cells, resulting in defected bladder epithelial barrier. Subsequent leakage of urinary potassium causes a stress response in the bladder and provokes cystitis.

Effects of long-term ketamine administration on rat bladder protein levels: a proteomic investigation using two-dimensional difference gel electrophoresis system.

OBJECTIVES: Long-term ketamine abuse can affect the urinary system, resulting in interstitial cystitis-like syndrome. However, its pathogenesis remains unclear. In the present study, a proteomic approach of two-dimensional difference gel electrophoresis followed by matrix-assisted laser desorption/ionization time-of-light mass spectrometry was carried out to investigate the potential disease-associated proteins in a rat model of ketamine-associated cystitis. METHODS: Rats were randomly assigned to control, normal saline, low dose of ketamine (10 mg/kg) and high-dose of ketamine (50 mg/kg) groups with six rats in each group. The two experimental groups were given ketamine hydrochloride i.p. daily, whereas the normal saline group rats were treated with saline. After 16 weeks of treatment, all bladders were excised, and samples from normal saline and high dose of ketamine groups were resolved in two-dimensional difference gel electrophoresis. Differentially expressed spots were excised and identified by matrix-assisted laser desorption/ionization time-of-light mass spectrometry. Phosphoprotein and non-phosphoprotein purification, histopathology, immunohistochemistry, and western blot were carried out in all groups. RESULTS: Histological study showed hyperplastic epithelium and inflammatory cells infiltration in the high dose of ketamine-treated rat bladders. Two-dimensional difference gel electrophoresis revealed 30 altered expressions between the normal saline and high dose of ketamine-treated group. Among these proteins, two upregulated and two downregulated protein spots were all identified as smooth muscle protein-22/transgelin. Immunohistochemical staining and western blot analysis showed that the expression of total transgelin had no significant difference between groups. However, the expression of phosphorylated transgelin in the low-dose and high dose of ketamine groups was increased, whereas the non-phosphorylated transgelin was decreased when compared with the normal saline group. CONCLUSIONS: Long-term ketamine abuse induces phosphorylation of transgelin in the bladder wall, and this might play an important role in the pathogenesis of ketamine-associated cystitis.