ABSTRACT
<p><b>BACKGROUND</b>Overactive bladder (OAB) can be caused by many factors such as inflammation, bladder outlet obstruction, neurogenic factors. We performed an intraperitoneal (ip) injection of cyclophosphamide to induce cystitis in rats, which causes their detrusors to overact, to provide a valuable disease model for discussing OAB pathogenesis and to study effective curing methods.</p><p><b>METHODS</b>Female Sprague-Dawley rats were induced to form cystitis by cyclophosphamide (200 mg/kg, ip). The day after the injection, two catheters were inserted into each rat's bladder to study its urodynamics. The BL-410 model bio-function experimental system was used to monitor bladder pressure while the rats were conscious. Unstable detrusor contractions appear in the urine storage period as a standard to determine OAB, and the positive rate was calculated. Urodynamic parameters such as bladder basal pressure (BP), maximum voiding pressure (MVP), intercontraction interval (ICI), spontaneous activity (SA), maximum cystometric capacity (MCC), and bladder compliance (BC) were recorded in each group, and a light microscope was used to observe the pathological changes in the rat bladder tissue.</p><p><b>RESULTS</b>The detrusor instability rate of the model group was 83.33%. The MVP, MCC and BC of rats in the model group were lower than the control group (P < 0.01), and the BP, ICI and SA of the model group rats were higher than the control group (P < 0.01). The difference between the control group and the model group is statistically significant. The model group rats' bladder walls swelled and bled, the submucosa thickened and leukocyte infiltration became serious.</p><p><b>CONCLUSIONS</b>Acute cystitis and OAB symptoms can be induced by ip injections of cyclophosphamide in rats. This can provide a valuable animal model to study OAB in human beings.</p>
Subject(s)
Animals , Female , Rats , Consciousness , Cyclophosphamide , Toxicity , Rats, Sprague-Dawley , Urinary Bladder, Overactive , Urodynamics , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To evaluate the safety and effectiveness of endourological techniques in the treatment of benign prostate hyperplasia (BPH) in aged high-risk patients.</p><p><b>METHODS</b>We used endourological techniques in the treatment of 283 BPH patients aged over 70 years and complicated with hydronephrosis, renal failure, heart failure, cerebral infarction, respiratory dysfunction, anemia, diabetes, bladder tumor, or prostate weight over 80 g, TURP (transurethral resection of the prostate) for 112 cases and PKRP (transurethral plasmakinetic resection of the prostate) for the other 171. All the patients were followed up for 1-30 months.</p><p><b>RESULTS</b>In the TURP group, the scores on IPSS and QOL were decreased from 27.5 +/- 2.8, 5.5 +/- 1.0 to 5.8 +/- 1.2, 1.0 +/- 0.5, and the residual urine volume (RUV) from (75.0 +/- 20.0) ml to (8.0 +/- 3.0) ml, but the maximal flow rate (Qmax) increased from (6.5 +/- 2.0) ml/s to (18.5 +/- 1.5) ml/s (P < 0.05), while in the PKRP group, the scores on IPSS and QOL were decreased from 28.2 +/- 2.2, 5.5 +/- 1.0 to 5.4 +/- 1.6, 1.0 +/- 0.5, and RUV from (80.0 +/- 20.0) ml to (7.0 +/- 3.0) ml, and Qmax increased from (6.8 +/- 2.1) ml/s to (20.0 +/- 1.5) ml/s (P < 0.05). There were no statistically significant differences in IPSS, QOL, Qmax and RUV after treatment between the two groups (P > 0.05), but significantly less complications were found in the PKRP than in the TURP group (P < 0.05).</p><p><b>CONCLUSION</b>Endourological treatment, especially PKRP, with comprehensive perioperative preparations, unerring operative skills, well-controlled operation time, and intensive postoperative monitoring and nursing, has the advantages of high safety, less bleeding, fewer complications and definite effectiveness for aged high-risk BPH patients.</p>
Subject(s)
Aged , Aged, 80 and over , Humans , Male , Prostatic Hyperplasia , General Surgery , Quality of Life , Transurethral Resection of Prostate , Methods , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To evaluate the application of CXC chemokine receptor-4 (CXCR4) combined with alpha-methylacyl-CoA racemase (P504S) or P63 protein in the differential diagnosis of benign and malignant prostatic diseases.</p><p><b>METHODS</b>The EnVision immunohistochemical method was used to detect the expressions of CXCR4, P504S and P63 protein in 40 specimens of PCa not treated by any anticancer therapy and 30 specimens of BPH tissues. The correlation was analyzed between CXCR4 expression and the characteristics of PCa metastasis.</p><p><b>RESULTS</b>Of the 40 cases of PCa, 33 (82.5%) were stained positive for CXCR4, 37 (92.5%) for P504S and 2 (5%) for P63 protein. Of the 30 cases of BPH, 5 (16.6%) exhibited positivity for CXCR4, 1 for P504S and all for P63. P504S + P63 showed a higher rate of correct diagnosis of PCa than either CXCR4 + P63 or P504S + CXCR4. There was a statistically significant correlation between CXCR4 expression and cancer metastasis (P < 0.05).</p><p><b>CONCLUSION</b>P504S, CXCR4 and P63 are useful tumor markers for the diagnosis and differentiation of benign and malignant prostatic diseases. CXCR4 gives a high rate of correct diagnosis when combined with P504S or P63, and has an important application value in the differential diagnosis of benign and malignant prostatic diseases.</p>
Subject(s)
Aged , Aged, 80 and over , Humans , Male , Middle Aged , Biomarkers, Tumor , Diagnosis, Differential , Membrane Proteins , Prostatic Hyperplasia , Diagnosis , Metabolism , Pathology , Prostatic Neoplasms , Diagnosis , Metabolism , Pathology , Racemases and Epimerases , Receptors, CXCR4ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of vardenafil in kidney transplant recipients with erectile dysfunction.</p><p><b>METHODS</b>Thirty-nine kidney transplant recipients with erectile dysfunction (ED) and serum creatinine values <2 mg/dl were enrolled in a 4-week randomized, double blind, placebo-controlled study, 19 treated with placebo and 20 with vardenafil. Vardenafil efficacy was assessed with the IIEF questionnaire after 4 weeks of treatment, and its safety appraised by measuring serum creatinine levels, creatinine clearances and cyclosporine concentrations before and after the treatment.</p><p><b>RESULTS</b>IIEF scores improved from 12.6 +/- 3.4 to 26.5 +/- 2.8 (P < 0.01), but renal function and cyclosporine concentrations remained unchanged in the vardenafil-treated patients. Adverse effects were observed in 4 patients: headache in 2, palpitation and flush in 1, and dyspepsia in the other.</p><p><b>CONCLUSION</b>Oral vardenafil therapy has a high efficacy and a low incidence of adverse events for kidney transplant recipients with ED.</p>
Subject(s)
Adult , Humans , Male , Middle Aged , Double-Blind Method , Erectile Dysfunction , Drug Therapy , Imidazoles , Therapeutic Uses , Kidney Transplantation , Phosphodiesterase Inhibitors , Therapeutic Uses , Piperazines , Therapeutic Uses , Renal Dialysis , Sulfones , Therapeutic Uses , Triazines , Therapeutic Uses , Vardenafil DihydrochlorideABSTRACT
<p><b>OBJECTIVE</b>To construct RNA interfering retrovirus vector targeting CXCR4 gene driven by human prostate-specific antigen promoter and investigate its targeted inhibition effects in androgen-responsive prostate cancer cells LNCaP.</p><p><b>METHODS</b>To clone the CXCR4 targeting siRNA gene by PCR. The PCR products were inserted into the pGensil-1 plasmid containing U6 promoter and EGFP. U6 promoter was replaced by hPSA promoter. Then, the recombinant EGFP-hPSA-siCXCR4 fragment was sub-cloned into pLXSN, which was evaluated by restriction enzyme. The pLXSN-EGFP-hPSA-siCXCR4 was transfected into PA317 cells with Lipofectamine 2000. The virus obtained from transfected PA317 cells was transfected into PC-3m, LNCaP and MCF-7 cells, respectively. The expression of CXCR4 mRNA and protein was detected by RT-PCR and Western blot. The invasion ability of prostate carcinoma cells was detected by Transwell experiment.</p><p><b>RESULTS</b>The recombinant pLXSN-hPSA-siCXCR4 was successfully constructed. The expression of CXCR4 mRNA and protein in LNCaP cells was blocked by pLXSN-hPSA-siCXCR4. The expression inhibition rate was (81.53 +/- 10.22)% at mRNA level detected by semi-quantitive RT-PCR and (90.52 +/- 9.31)% at protein level detected by Western blot, respectively, in LNCaP cells at 48 h. The expression of CXCR4 mRNA and protein was effectively inhibited by sequence-specific hPSA-siCXCR4 in LNCaP cells, but not in PC-3m and MCF-7 cells. The results of Transwell experiment showed that the number of cells in down-pore of micro-membrane was 139.9 +/- 14. 2 in the treated group, significantly less in comparison with 348.4 +/- 36. 4 in the controlled group (P < 0.05). However, the number of PC-3m and MCF-7 cells in down-pore of micro-membrane was not significantly different among the control and treated groups (P > 0.05).</p><p><b>CONCLUSION</b>The downstream siRNA controlled by hPSA promoter in retrovirus system can be expressed selectively in androgen-responsive prostate carcinoma cells, showing an apparent targeting character. RNAi targeted to CXCR4 driven by hPSA promoter has a potential value in gene therapy of androgen-responsive prostate cancer.</p>
Subject(s)
Animals , Humans , Male , Mice , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Genetic Vectors , NIH 3T3 Cells , Neoplasm Invasiveness , Plasmids , Promoter Regions, Genetic , Prostate-Specific Antigen , Genetics , Prostatic Neoplasms , Genetics , Metabolism , Pathology , RNA Interference , RNA, Messenger , Metabolism , RNA, Small Interfering , Genetics , Receptors, CXCR4 , Genetics , Metabolism , Recombinant Proteins , Genetics , Metabolism , Retroviridae , Genetics , TransfectionABSTRACT
<p><b>OBJECTIVE</b>To investigate the phosphorylation intensity of MAPK pathway molecular Erk1/2 and the proliferation of prostate cancer cell line PC-3M.</p><p><b>METHODS</b>Flow cytometry and RT-PCR were employed to study the ratio of different cell cycles and phases, respectively, before and after GM-CSF stimulation. Erk1/2 phosphorylation intensity was examined by Western blot simultaneously.</p><p><b>RESULTS</b>The rate of PC-3M cells at S and G2/M stages and the expression intensity of Ki-67 increased after GM-CSF incubation in a dose-dependent manner. The phosphorylation intensity of Erk1/2 increased remarkably after stimulation with GM-CSF.</p><p><b>CONCLUSION</b>The intensification of Erk1/2 phosphorylation is one important molecular mechanism of the proliferation of hormone-independent prostate cancer.</p>
Subject(s)
Humans , Male , Cell Line, Tumor , Cell Proliferation , Granulocyte-Macrophage Colony-Stimulating Factor , Pharmacology , Ki-67 Antigen , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase Kinases , Metabolism , Physiology , Neoplasms, Hormone-Dependent , Metabolism , Pathology , Phosphorylation , Prostatic Neoplasms , Metabolism , Pathology , Signal TransductionABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of the levels of IGF-I in the epididymis and the expression of IGF-I in the testis of adult male rat after the administration of cyclophosphamide.</p><p><b>METHODS</b>Ninety-six male adult rats (8 weeks age) were divided into 6 groups. The doses given to the rats of the groups 1 to 5 were 10, 20, 40, 80 and 100 mg/(kg x d), respectively. The remaining group was served as control. All those rats were sacrificed and IGF-I were quantitatively determined by ELISA techniques 2 and 4 weeks after the administration of the drug (by gastric fudge). Immunohistochemical SP technique was used to examine expression of IGF-I in rat testis.</p><p><b>RESULTS</b>The levels of cell factors (IGF-I) in the epididymis of the rats were gradually reduced with the increasing time and dose after administration of the drug. In the mean time the expression of IGF-I in the tissues of the testis of those rats were also gradually reduced.</p><p><b>CONCLUSION</b>In the time of oligozoospermia/azoospermia induced by the administration of cyclophosphamide, the expression levels of IGF-I in the genetic system were significantly reduced. The possible mechanism of these changes could be attributed to the lower spermatogenesis function of the testis caused by the administration of cyclophosphamide.</p>
Subject(s)
Animals , Male , Rats , Azoospermia , Metabolism , Cyclophosphamide , Toxicity , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Epididymis , Metabolism , Immunohistochemistry , Insulin-Like Growth Factor I , Oligospermia , Metabolism , Rats, Sprague-Dawley , Testis , MetabolismABSTRACT
<p><b>OBJECTIVES</b>To examine the effects of suramin on the growth, cell cycle and apoptosis of a hormone refractory prostate cancer cell line PC-3M, and to explore the possible mechanisms.</p><p><b>METHODS</b>The roles of diverse concentrations (10, 50, 100 and 200 mumol/L) of suramin on PC-3M cell proliferation at different ratios of fetal calf serum (FCS) (2%, 5%, 10%) were assayed respectively by trypan blue exclusion and tetrazolium (MTT) assay. The effect of suramin on cell cycle distribution and apoptosis induction of PC-3M cells was evaluated with flow cytometry (FCM).</p><p><b>RESULTS</b>A higher dosage of suramin (200 mumol/L) had a cytotoxic effect on PC-3M cells, while lower dosages from 10 to 100 mumol/L produced a predominant inhibiting effect. Suramin could also play a growth suppressive role in the culture media containing 10% FCS, but to a much less extent than in the media containing lower concentrations(5%, 2%) of FCS. FCM analysis exhibited that suramin at a high dosage of 200 mumol/L could induce apoptosis, and at the other concentrations, G0/G1 cell cycle arrest.</p><p><b>CONCLUSION</b>Suramin's proliferative suppression on PC-3M cells might result from several mechanisms including antagonistic action on growth stimulation via growth factor, arrest of cell cycle and induction of apoptosis.</p>