Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be associated with inflammatory diseases, such as infections, autoimmune diseases, and cancers. Meanwhile, TLR10, which can form heterodimers with TLR2, has been considered an orphan receptor without an exact function. The present study therefore aims to examine the effects of TLR2 and TLR10 on PI. Prostate samples and clinical data were obtained from the patients diagnosed with benign prostatic hyperplasia. The inflammatory cell model was established by adding lipopolysaccharide to RWPE-1 cells. Prostate tissues/cells were examined by histological, molecular, and biochemical approaches. Both TLR2 and TLR10 were found to be expressed in prostate tissues and RWPE-1 cells. mRNA/protein expression levels of TLR2 and TLR10 were both positively correlated with prostate tissue inflammatory grades. Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phospho-nuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65), interleukin (IL)-6, and IL-8 than control cells. Moreover, HMGB1, phospho-NF-κB P65, IL-6, and IL-8 were downregulated after TLR2 knockdown and upregulated after TLR10 knockdown in RWPE-1 cells. TLR2 stimulation can activate the inflammatory signaling cascade in prostate epithelial cells. Conversely, TLR10 exhibited suppressive effects on inflammation. With antagonistic functions, both TLR2 and TLR10 were involved in PI. TLR10 could be a novel target in modulating inflammatory signal transduction of prostate epithelial cells.
Aged ; Cell Line ; Cytokines/metabolism* ; Epithelial Cells/pathology* ; Humans ; Inflammation/pathology* ; Lipopolysaccharides/pharmacology* ; Male ; Middle Aged ; Phosphorylation/drug effects* ; Prostate/pathology* ; Prostatic Hyperplasia/pathology* ; Signal Transduction/drug effects* ; Toll-Like Receptor 10/metabolism* ; Toll-Like Receptor 2/metabolism* ; Up-Regulation

OBJECTIVETo investigated the anti-inflammatory and antimicrobial effects of anthocyanins extracted from black soybean on the chronic bacterial prostatitis (CBP) rat model.

METHODSThe Sprague-Dawley rats were divided into 4 groups, including control, ciprofloxacin, anthocyanins and anthocyanins with ciprofloxacin groups (n=8 in each group). Then, drip infusion of bacterial suspension (Escherichia coli Z17 O:K:H) into Sprague-Dawley rats was conducted to induce CBP. In 4 weeks, results of prostate tissue, urine culture, and histological analysis on the prostate were analyzed for each group.

RESULTSThe use of ciprofloxacin, anthocyanins, and anthocyanins with ciprofloxacin showed statistically significant decreases in bacterial growth and improvements in the reduction of prostatic inflammation compared with the control group (P<0.05). The anthocyanins with ciprofloxacin group showed a statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the ciprofloxacin group (P<0.05).

CONCLUSIONSThese results suggest that anthocyanins may have anti-inflammatory and antimicrobial effects, as well as a synergistic effect with ciprofloxacin. Therefore, we suggest that the combination of anthocyanins and ciprofloxacin may be effective in treating CBP to obtain a higher rate of treatment success.

Acinar Cells ; drug effects ; pathology ; Animals ; Anthocyanins ; isolation & purification ; pharmacology ; therapeutic use ; Anti-Infective Agents ; pharmacology ; therapeutic use ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Chronic Disease ; Disease Models, Animal ; Escherichia coli Infections ; drug therapy ; urine ; Fibrosis ; Inflammation ; pathology ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Prostate ; drug effects ; microbiology ; pathology ; Prostatitis ; drug therapy ; microbiology ; urine ; Rats, Sprague-Dawley ; Severity of Illness Index ; Soybeans ; chemistry ; Urine ; microbiology

ObjectiveTo investigate the effects of fosfomycin tromethamine (FT) on the expressions of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6) in the prostate tissue of the rats with chronic bacterial prostatitis (CBP).

METHODSWe randomly divided 70 male SD rats into 7 groups of equal number: blank control, CBP model control, positive control, 14 d low-dose FT, 7 d low-dose FT, 14 d high-dose FT, and 7 d high-dose FT. The CBP model rats in the latter five groups were treated intragastrically with levofloxacin at 100 mg/kg/d for 30 days and FT at 200 mg/kg/d for 14 and 7 days and at 300 mg/kg/d for 14 and 7 days, respectively. Then we collected the prostate tissue from the animals for determination of the levels of TNF-α, IL-8 and IL-6 by ELISA.

RESULTSCompared with the blank controls, the CBP model rats showed significantly increased levels of TNF-α (［19.83 ± 6.1］ vs ［32.93 ± 6.21］ ng/g prot, P <0.01), IL-8 (［8.26 ± 0.52］ vs ［16.2 ± 2.84］ ng/g prot, P <0.01) and IL-6 (［1.55 ± 0.11］ vs ［2.51 ± 1.06］ ng/g prot, P <0.05) in the prostate tissue. In comparison with the CBP model controls, the levels of TNF-α and IL-8 were remarkably decreased in the groups of positive control (［20.54 ± 5.78］ ng/g prot, P <0.01; ［12.43 ± 4.02］ ng/g prot, P <0.05), 14 d low-dose FT (［21.95 ± 6.48］ ng/g prot, P <0.01; ［11.11 ± 2.86］ ng/g prot, P <0.01), 7 d low-dose FT (［23.8 ± 6.93］ ng/g prot, P <0.05; ［12.43 ± 4.02］ ng/g prot, P <0.05), 14 d high-dose FT (［19.97 ± 2.58］ ng/g prot, P <0.01; ［8.83 ± 1.32］ ng/g prot, P <0.01), and 7 d high-dose FT (［21.97 ± 3.38］ ng/g prot, P <0.01; ［12.68±1.97］ ng/g prot, P <0.05). No statistically significant differences were observed between the positive control and FT groups in the contents of TNF-α, IL-8 or IL-6 (P >0.05). The expression of IL-6 was markedly reduced in the 14 d high-dose FT group as compared with the model controls (［1.76 ± 0.46］ vs ［2.51 ± 1.06］ ng/g prot, P<0.05) but exhibited no significant difference between the CBP model control and the other groups (P >0.05).

CONCLUSIONSFosfomycin tromethamine inhibits the expressions of TNF-α, IL-8 and IL-6 in the prostate tissue, suppresses its inflammatory reaction, promotes the repair of damaged prostatic structure, and thus contributes to the treatment of chronic bacterial prostatitis in rats.

Animals ; Anti-Bacterial Agents ; pharmacology ; Bacterial Infections ; drug therapy ; microbiology ; Fosfomycin ; pharmacology ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Levofloxacin ; pharmacology ; Male ; Prostate ; drug effects ; metabolism ; Prostatitis ; drug therapy ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

ObjectiveTo evaluate the effect of cefoxitin prophylactic in reducing the incidence of severe infection after transrectal prostate biopsy (TRPB).

METHODSThis retrospective study included 155 cases of TRPB with a 5-day administration of oral levofloxacin at 200 mg bid (the control group) and another 167 cases with a 3-day administration of oral levofloxacin at the same dose plus intravenous cefoxitin at 2.0 g 2 hours before TRPB (the experimental group) according to the distribution characteristics of drug-resistance bacteria in our department. The patients of the control and experimental groups were aged (68.68 ± 8.12) and (68.72 ± 7.51) years, with PSA levels of (19.78 ± 21.57) and (21.15 ± 42.63) μg/L, involving (11.68 ± 1.44) and (11.77±1.02) biopsy cores, respectively. Comparisons were made between the two groups of patients in the incidence rate of severe infection, which was defined as lower urinary track symptoms plus the systemic inflammatory response syndrome (SIRS) within 7 days after TRPB.

RESULTSThe incidence rate of postoperative severe infection was significantly lower in the experimental group than in the control (0.6% ［1/167］ vs 5.8% ［9/155］, P < 0.05). Blood cultures revealed positive E-coli strains in 6 cases in the control group, including 5 ESBL-positive and 4 quinolone-resistant and amikacin-sensitive cases, all sensitive to cefoxitin, cefoperazone/sulbactam and imipenem. The only one case of severe infection was shown to be negative in blood culture.

CONCLUSIONSPreoperative intravenous administration of cefoxitin according to the specific distribution characteristics of drug-resistance bacteria can significantly reduce the incidence of severe infection after TRPB.

Aged ; Anti-Bacterial Agents ; therapeutic use ; Biopsy ; adverse effects ; methods ; Cefoxitin ; therapeutic use ; Drug Resistance, Bacterial ; Escherichia coli ; isolation & purification ; Escherichia coli Infections ; microbiology ; prevention & control ; Humans ; Levofloxacin ; therapeutic use ; Male ; Middle Aged ; Postoperative Complications ; blood ; prevention & control ; Prostate ; pathology ; Retrospective Studies

PURPOSE: To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). MATERIALS AND METHODS: We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. RESULTS: There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. CONCLUSION: We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals.
Anti-Bacterial Agents ; Canada ; Data Mining ; Drug Eruptions ; Drug Labeling ; Drug-Related Side Effects and Adverse Reactions ; France ; Germany ; Heart Arrest ; Heart Failure ; Hypokalemia ; Imipenem* ; Italy ; Japan ; Korea* ; Myocardial Infarction ; Odds Ratio ; Pharmacoepidemiology ; Pharmacovigilance ; Prostate ; Switzerland

Benign prostatic hyperplasia (BPH) is an age-related disease of unknown etiology, characterized by prostatic enlargement coincident with distinct alterations in tissue histology. In the present study, we investigated whether triptolide can prevent testosterone-induced prostatic hyperplasia in rats. Castration was performed via the scrotal route after urethane aesthesia. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP) for two weeks. Triptolide was administered daily by oral gavage at a dose of 100 and 50 μg·kg for 2 weeks, along with the TP injections. On day 14, the animals were humanely killed by cervical dislocation after aesthesia. Prostates were excised, weighed, and used for histological studies. Testosterone and dihydrotestosterone (DHT) levels in serum and prostate were measured. The results showed that triptolide significantly reduced the prostate weight, and the testosterone and DHT levels in both the serum and prostate. Histopathological examination also showed that triptolide treatment suppressed TP-induced prostatic hyperplasia. In conclusion, triptolide effectively inhibits the development of BPH induced by testosterone in a rat model.
Androgens ; blood ; Animals ; Diterpenes ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Epoxy Compounds ; administration & dosage ; Humans ; Male ; Phenanthrenes ; administration & dosage ; Prostate ; drug effects ; growth & development ; Prostatic Hyperplasia ; blood ; drug therapy ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood ; Tripterygium ; chemistry

Objective: To study the effects of muskolibanum combination on the proliferation and differentiation of prostate stem cells. METHODS: We cultured prostate epithelial cells and urogenital sinus mesenchymal (UGSM) cells from 7－10 d old C57BL/6 mice and 16－18 d old pregnant C57BL/6 mice, transplanted the mixed suspension of the two types of cells under the kidney envelope of SCIDCB.17 male mice, and harvested the transplants 30 days later. We randomly divided the SCIDCB.17 mice into four groups to be treated intragastrically with musk (n = 8), olibanum (n = 8), musk+olibanum (n = 7), and normal saline (blank control, n = 8)) respectively, all for 14 days. Then we collected the kidney tissue for observation of the morphology of the glandular tubes and differentiation of different subsets of stem cells by HE staining and determination of the expressions and distribution of P63, CD133, CD117 and Sca1 by immunohistochemistry and Western blot. RESULTS: A system was successfully established for the isolation and mixed culture of Sca1 Lin+ CD49f+ (LSC) cells of prostate stem cells and UGSM cells of the mouse embryonic prostate. Immunohistochemistry showed positive expressions of P63, CD133, Sca1, and CD117 in the prostatic acinar epithelia and proved the presence of prostatic acinar epithelial structure in the transplants. Compared with the blank control group, the expressions of CD133, Sca1 and CD117 were significantly increased in the musk, olibanum, and musk+olibanum groups (P< 0.05), higher in the musk+olibanum than in the musk or olibanum group (P< 0.05), and their protein expressions were even more elevated in the musk+olibanum group (P< 0.01), with statistically significant difference from the olibanum group (P< 0.05). CONCLUSIONS The combination of musk and olibanum can improve the proliferation and differentiation of prostate stem cells.
Animals ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Drug Therapy, Combination ; Epithelial Cells ; cytology ; drug effects ; Fatty Acids, Monounsaturated ; pharmacology ; Female ; Frankincense ; pharmacology ; Male ; Mesenchymal Stem Cells ; cytology ; drug effects ; Mice ; Mice, Inbred C57BL ; Mice, SCID ; Pregnancy ; Prostate ; cytology ; Random Allocation ; Receptor Protein-Tyrosine Kinases ; Receptors, Cholinergic ; Stem Cells ; cytology ; drug effects

Objective: To explore the effects of Xialiqi Capsules(XLQ) on the expressions of the proliferating cell nuclear antigen (PCNA) and caspase-3 in the prostate tissue of the BPH rat model. METHODS: Fifty male SD ratswereequally randomized into groups A (sham operation control), B (BPH model control), C (high-dose XLQ), D (low-dose XLQ), and E (finasteridecontrol) andthe BPH modelswere established by subcutaneous injection of testosterone propionate at 0.5 mg per kilogram of the body weight per day for 30 days after castration. After modeling, the animals in groups A and B were treated intragastricallywith normal saline, while those in C, D, and E with XLQ at 1.20 and 0.61 g per kilogram of the body weight per day or finasterideat 0.8 mg per kilogram of the body weight per day, respectively, all for 30 days. Then,the bilateral prostates were harvestedfrom the rats for calculation of the prostatic index (prostate wet weight/ body weight) and determination of the expressions of PCNA and caspase-3 in the prostate tissue by immunohistochemistry and immunofluorescence staining, respectively. RESULTS: The prostate wet weight and prostate index were significantly increased in group B as compared with group A, (［1326±60］ vs［471±17］ g, P<0.01; ［2.89±0.18］ vs ［1.06±0.06］ mg/g, P<0.01), but decreased in groups C (［914±36］ g;［2.02±0.08］ mg/g), D (［1 099±46］g;［2.39±0.11］ mg/g), and E (［817±53］ g;［1.83±0.10］ mg/g)in comparison with B (P<0.01), with statistically significant differences among groups C, D, and E(P<0.01) and most significantly in E.The PCNA level in the prostate tissue wasremarkably higher in group B than in A, but lower in groups C, D and E than in B. The expression of caspase-3 was down-regulatedin group B as compared with A, but up-regulated in groups C, D and E in comparison with B, most significantly in E. CONCLUSIONS Xialiqi Capsules can effectively reduce the prostate wet weight and prostatic index of in rats with BPH by inhibiting the level of PCNA and promoting the expression of caspase-3.
Animals ; Capsules ; Caspase 3 ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Finasteride ; administration & dosage ; pharmacology ; Male ; Orchiectomy ; Organ Size ; drug effects ; Proliferating Cell Nuclear Antigen ; metabolism ; Prostate ; drug effects ; metabolism ; pathology ; Prostatic Hyperplasia ; drug therapy ; metabolism ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Urological Agents ; administration & dosage ; pharmacology

Co-administration of tadalafil and tamsulosin HCl in patients with benign prostate hyperplasia and erectile dysfunction is increasing in clinical settings. Development of fixed-dose combination (FDC) of tadalafil and tamsulosin HCl could contribute to improving patients' adherence and treatment efficacy. We evaluated the pharmacokinetics and safety profiles of a newly developed fixed-dose combination capsule of tadalafil 5 mg/tamsulosin HCl 0.4 mg in comparison with co-administration of each formulation in healthy volunteers under fasted and fed conditions. Two randomized, open-label, single-dose, two-way, crossover studies were completed in 29 subjects under fasted condition, and 33 subjects under fed condition. Serial blood sample collection for PK analysis was conducted up to 72 hours after dosing, and PK parameters were calculated using non-compartmental analysis. Geometric mean ratios and 90% confidence intervals of the C(max) and AUC(last) were used to evaluate comparative bioavailability. In both fasted and fed condition studies, the bioequivalence was established. The most common adverse drug reactions were orthostatic hypotension and headache with no statistical difference between treatment groups. All subjects with orthostatic hypotension recovered at follow-up test. Although changes in vital signs from baseline were statistically significant, there were no subjects with systolic blood pressure < 90 mmHg and there were no clinically meaningful signs or symptoms associated. FDC of tadalafil and tamsulosin HCl can be an alternative to co-administration of individual drugs for providing better compliance. Changes in blood pressure should be kept in mind when tadalafil and tamsulosin HCl are co-administered in clinical settings.
Biological Availability ; Blood Pressure ; Compliance ; Cross-Over Studies ; Drug-Related Side Effects and Adverse Reactions ; Erectile Dysfunction ; Follow-Up Studies ; Headache ; Healthy Volunteers* ; Humans ; Hyperplasia ; Hypotension, Orthostatic ; Male ; Pharmacokinetics* ; Prostate ; Tadalafil ; Therapeutic Equivalency ; Treatment Outcome ; Vital Signs

This study investigated the effect of diosgenin, a natural sapogenin possessing various pharmacological activities, on benign prostatic hyperplasia (BPH) in rats and the possible mechanisms. BPH was established in the castrated rats by subcutaneous injection of testosterone propionate. Animals were randomly divided into four groups (n=10 each): model group (0.5% sodium carboxymethyl cellulose); positive control group (3 mg/kg finasteride); two diosgenin groups (50 and 100 mg/kg). The drugs were intragastricaly given in each group for consecutive 3 weeks. Another 10 rats with no testicles cut off served as negative controls and they were subcutaneously injected with 0.1 mL olive oil per day and then treated with 0.5% sodium carboxymethylcellulose. After 3-week administration, the prostate index and serum PSA level were determined, and histopathological examination was carried out. The levels of MDA, SOD and GPx in prostates were also measured. Additionally, the expression of Bcl-2, Bax and p53 was examined using Western blotting. The results showed that the prostate index and serum PSA level were significantly decreased, and the pathological changes of the prostate gland were greatly improved in diosgenin groups as compared with the model group. Elevated activities of SOD and GPx, and reduced MDA level were also observed in diosgenin-treated rats. In addition, the expression of Bcl-2 in prostates was down-regulated, whereas that of Bax and p53 was up-regulated in diosgenin-treated rats. These results indicated that diosgenin was effective in inhibiting testosterone propionate-induced prostate enlargement and may be a candidate agent for the treatment of BPH.
Animals ; Apoptosis ; Diosgenin ; pharmacology ; therapeutic use ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; Prostate ; drug effects ; metabolism ; Prostate-Specific Antigen ; blood ; Prostatic Hyperplasia ; drug therapy ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Tumor Suppressor Protein p53 ; metabolism ; bcl-2-Associated X Protein ; metabolism