The prostate gland, like other glandular organs, is rich in blood and lymphatic vessels and nerves, which are the important histological factors for obtaining nutrition as well as for the endocrine and exocrine functions of the glands. Antimicrobial and non-antimicrobial drugs administered to patients by the oral, IM, IV or even topical routes are absorbed into the blood and transported to the prostate and other organs, where they can diffuse into the extravascular tissues through the walls of normal and damaged capillaries. The permeability of the prostate is enhanced by inflammatory reactions in the prostatic tissue, which is responsible for exudation or leakage of leukocytes and red blood cells, and drugs in the blood can enter the extravascular tissue of the prostate as well as diffuse into the prostatic secretions. The prostate lesions in patients with prostatitis or other prostatic diseases are caused by different types of pathogenic agents with various properties, and these diseases are characterized by a longer process of damage and a variety of pathological changes. Therefore, the diagnosis and treatment of prostatitis are relatively complex and difficult challenges hut meanwhile simple and easy matters for clinicians, and the difficulty or easiness is related not to the drug penetrability of the prostate, but largely to the understanding of the biological properties of the pathogenic agents, the physiological and pathological conditions of the patient's body and prostate, and the properties of drugs. The common factors that cause difficult treatment of prostatitis include clinical and laboratory misdiagnoses, release of pathogenic agents within pyogenic or necrotic prostatic tissues, variation of pathogenic agents, reinfection by other pathogens, and choice and administration of drugs.
Anti-Bacterial Agents ; pharmacokinetics ; therapeutic use ; Humans ; Male ; Prostate ; drug effects ; microbiology ; pathology ; Prostatitis ; diagnosis ; microbiology ; pathology

OBJECTIVETo evaluate the effects of red clover isoflavones on the proliferation and apoptosis of human benign prostatic hyperplasia (BPH) stromal cells.

METHODSWe treated human prostate stromal cells with red clover isoflavones at the concentration of 12.5, 25, 50 and 100 microg/ml, and established a PBS blank control, a dimethyl sulphoxide (DMSO) negative control and four finasteride positive control groups (at the concentration of 12.5, 25.0, 50.0 and 100.0 microg/ml). We determined the effects of different concentrations of red clover isoflavones on the proliferation of the cells by MTT assay and on their apoptosis by Annexin V/PI double staining flow cytometry.

RESULTSRed clover isoflavones inhibited the proliferation of the BPH stromal cells by 18.86% at 25.0 microg/ml, compared with 5.17% in the blank control group (P < 0.05), and more obviously at a higher concentration. At 50.0 microg/ml, red clover isoflavones exhibited a weaker inhibitory effect than finasteride (28% vs 69.88% , P < 0.05). Annexin V/PI double staining flow cytometry showed that red clover isoflavones at 25.0 microg/ml induced the apoptosis of the prostate stromal cells by (18.54 +/- 2.5)%, with significant differences from the negative control and blank control (P < 0.01).

CONCLUSIONRed clover isoflavones can inhibit the proliferation and promote the apoptosis of human BPH stromal cells.

Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Humans ; Isoflavones ; pharmacology ; therapeutic use ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Prostate ; cytology ; drug effects ; Prostatic Hyperplasia ; drug therapy ; pathology ; Stromal Cells ; drug effects ; Trifolium ; chemistry

OBJECTIVETo investigate whether 5alpha-reductase inhibitor and dihydrotestosterone (DHT) play a role in spermatogenesis in male rats.

METHODSThirty-two male rats were divided into 4 groups (Groups C, T, F and FT). Group C received plant oil injection and oral starch perfusion, Group T testosterone undecanoate (TU, 20 mg/kg) injection and oral starch perfusion, Group F plant oil injection and oral Finasteride perfusion, and Group FT TU (20 mg/kg) injection and oral Finasteride perfusion. Data on serum T and DHT, sperm count, sperm mobility and reproductive function were collected and analysed.

RESULTS(1) 5alpha-reductase inhibitor, Finasteride and TU reduced the weight of the testis and epididymis in the experiment groups compared with the negative control (Group C), but TU increased the weight of the prostate while Finasteride decreased it compared with the positive control (Group T). TU combined with Finasteride could counteract the effect of the weight increase of the prostate, but not that of the testis. (2) Finasteride, or Finasteride combined with TU, reduced the DHT but increased the testosterone level in comparison with the control group. (3) Both Finasteride and TU could inhibit epididymal sperm count and reproductive function compared with the control, but the effect was less significant in Group FT than in Group F.

CONCLUSIONHigh dosages of 5alpha-reductase inhibitor, Finasteride, can suppress male reproductive function, but the inhibiting effect could be counteracted by administration of 5alpha-reductase inhibitor along with TU.

Animals ; Cholestenone 5 alpha-Reductase ; antagonists & inhibitors ; Dihydrotestosterone ; pharmacology ; Dose-Response Relationship, Drug ; Finasteride ; pharmacology ; Male ; Organ Size ; Prostate ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley ; Spermatogenesis ; drug effects ; Testis ; drug effects ; pathology ; Testosterone ; analogs & derivatives ; pharmacology

OBJECTIVETo investigate the effects of intraprostatic injection of botulinum toxin A (BTX-A) on benign prostate hyperplasia (BPH) in rats.

METHODSModels of BPH were established in adult male Sprague-Dawley rats by injection of testosterone propionate, and then divided into three BTX-A groups, injected with BTX-A into the ventral prostate at the doses of 5 U, 10 U and 20 U, a negative control group, injected with saline only, and a sham operation group, with 12 in each. The prostates of the animals were harvested at 2 or 4 weeks after the injection, their volumes and weights measured, histological changes examined by HE staining, and glandular and interstitial areas semi-quantified by the image analysis system.

RESULTSTwo rats died in the 20 U group within 3 days after BTX-A injection. Compared with the saline group, the 5 U, 10 U and 20 U BTX-A groups showed significant decreases in prostatic volume (P < 0.01, 0.01 and 0.05), weight, and glandular and interstitial areas as well as atrophic epithelia in the glandular tube at 2 weeks. These changes were lessened at 4 weeks, especially in the 5 U group.

CONCLUSIONIntraprostatic injection of BTX-A induces obvious atrophy and histological changes of the prostate, but meanwhile may potentially result in death at a large dose.

Animals ; Botulinum Toxins, Type A ; administration & dosage ; therapeutic use ; toxicity ; Male ; Prostate ; drug effects ; pathology ; Prostatic Hyperplasia ; drug therapy ; pathology ; Rats ; Rats, Sprague-Dawley

AIMTo investigate the activity of RRR-alpha-tocopheryloxybutyric acid (TOB), an ether analog of RRR-alpha-tocopheryl succinate (VES), in prostate cancer cells.

METHODSVES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rv1 cells and primary-cultured prostate fibroblasts. The proliferation rates were determined by MTT assay, the cell viabilities were determined by trypan blue exclusion assay, and the cell deaths were evaluated by using Cell Death Detection ELISA kit. The protein expression levels were determined by Western blot analysis.

RESULTSThe MTT growth assay demonstrated that TOB could effectively suppress the proliferation of prostate cancer cells, but not normal prostate fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB and VES suppressed prostate-specific antigen (PSA) at the transcriptional level leading to reduced PSA protein expression. Furthermore, vitamin D receptor (VDR) expression increased after the addition of TOB.

CONCLUSIONOur data suggests that the VES derivative, TOB, is effective in inhibiting prostate cancer cell proliferation, suggesting that TOB could be used for both chemopreventive and chemotherapeutic purposes in the future.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Division ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cells, Cultured ; Fibroblasts ; cytology ; drug effects ; Humans ; Kinetics ; Male ; Prostate ; cytology ; Prostatic Neoplasms ; pathology ; Vitamin E ; analogs & derivatives ; pharmacology

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

PURPOSE: We conducted a prospective single-center study to evaluate the possibility of discontinuation of dutasteride after combination therapy with an alpha blocker for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We prospectively treated BPH patients with an alpha blocker and dutasteride (0.5 mg/d). Patients who had been treated with alpha blockers against BPH for more than 2 months were eligible, and 20 patients were included in the study. After 6 months of combination therapy, dutasteride was discontinued. Patients were followed for 12 months after cessation. Prostate volume, intraprostatic architecture determined by transrectal ultrasound, peak urinary flow rate, postvoid residual urine volume, and the serum prostate-specific antigen level were evaluated every 6 months, and the International Prostate Symptom Score and overactive bladder symptom score (OABSS) every 3 months. Patients were allowed to restart dutasteride during the follow-up period according to their desire. RESULTS: Twelve patients (12/20, 60%) restarted the combination therapy from 6 to 12 months into the follow-up period. For patients who restarted dutasteride, the prostate volume and OABSS had increased and worsened after discontinuation, respectively. A visible transition zone with a clear border on transrectal ultrasound at baseline and regrowth of the prostate after discontinuation of dutasteride were risk factors for restarting the therapy (Mann-Whitney U test: p=0.008, p=0.017). CONCLUSIONS: Prostatic enlargement after discontinuation of dutasteride differs among patients. Rapid regrowth of the prostate leads to deterioration of storage symptoms and a tendency to restart dutasteride. Baseline intraprostatic architecture may be a predictive factor for whether the patient is a good candidate for discontinuation.
5-alpha Reductase Inhibitors/administration & dosage/adverse effects ; *Adrenergic alpha-Antagonists/administration & dosage/adverse effects ; Aged ; Drug Monitoring ; Drug Therapy, Combination/methods ; *Dutasteride/administration & dosage/adverse effects ; Follow-Up Studies ; Humans ; Japan ; Male ; Middle Aged ; Organ Size ; Prospective Studies ; *Prostate/drug effects/pathology/ultrasonography ; Prostate-Specific Antigen/analysis ; *Prostatic Hyperplasia/drug therapy/pathology ; Secondary Prevention/methods/statistics & numerical data ; Treatment Outcome ; Withholding Treatment

AIMTo determine the effect of two different extracts of red maca in male rats.

METHODSProstatic hyperplasia was induced in male rats with testosterone enanthate (TE). The study comprised six groups: one control group (group 1), one group treated with TE (group 2), two groups treated with TE and aqueous extract of red maca (groups 3 and 4), one group treated with hydroalcoholic extract of red maca (group 5) and one group treated with finasteride (0.1 mg, group 6). Differences in the aqueous extract dependent on the length of time of boiling, whether for 2 or 3 hours, for groups 3 and 4 was assessed. Extracts of red maca contained 0.1 mg of benzylglucosinolate. Thereafter, a dose-response effect of different doses of benzylglucosinolates (0.02-0.08 mg) in red maca extracts was assessed.

RESULTSProstate weight was similar in rats treated with freeze-dried aqueous extract of red maca prepared after 2 and 3 hours of boiling. Freeze-dried aqueous extract of red maca, hydroalcoholic extract of red maca and finasteride reduced prostate weight in rats with prostatic hyperplasia. No difference was observed between the data obtained from aqueous extract or hydroalcoholic extract of red maca. A dose dependent reduction of prostate weight was observed with the increase of the dose of benzylglucosinolates in red maca extracts.

CONCLUSIONThe present study showed that hydroalcoholic or aqueous extract of red maca containing 0.1 mg of benzylglucosinolate can reduce prostate size in male rats in which prostatic hyperplasia had been induced by TE.

Alcohols ; Animals ; Finasteride ; therapeutic use ; Lepidium ; Male ; Organ Size ; drug effects ; Plant Extracts ; therapeutic use ; Prostate ; drug effects ; pathology ; Prostatic Hyperplasia ; chemically induced ; drug therapy ; pathology ; Rats ; Testosterone ; analogs & derivatives ; Thiocyanates ; analysis ; pharmacology ; Thioglucosides ; analysis ; pharmacology ; Water

OBJECTIVETo study the incidence of benign prostatic hyperplasia (BPH) complicated by chronic prostatitis.

METHODSWe performed routine examinations and bacterial culture of the expressed prostate secretion (EPS) for 213 cases of BPH, detected mycoplasma, chlamydia and serum PSA, and compared the results of IPSS of those complicated with chronic prostatitis before and after a 4-week anti-inflammatory treatment.

RESULTSOf the total cases, 69 (32.4%) were complicated by chronic prostatitis, 27 (12.7%) EPS positive and 15 (7.0%) mycoplasma and chlamydia positive. Among the 69 cases of chronic prostatitis, 7 were found with an elevated level of PSA (> 4 microg/L), and 43 with the mean IPSS score decreased from (12.2 +/- 2.6) before anti-inflammatory treatment to (10.5 +/- 2.3) after it (P < 0.01).

CONCLUSIONEPS examination should be performed for patients with BPH, which is highly significant for the diagnosis of prostatitis, choice of medical or surgical treatment, improvement of therapeutic effect and reduction of complications.

Aged ; Aged, 80 and over ; China ; epidemiology ; Chlamydia ; isolation & purification ; Chronic Disease ; Humans ; Incidence ; Male ; Middle Aged ; Mycoplasma ; isolation & purification ; Prostate ; drug effects ; microbiology ; pathology ; Prostate-Specific Antigen ; blood ; Prostatic Hyperplasia ; complications ; drug therapy ; epidemiology ; Prostatitis ; blood ; complications ; microbiology

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, NIH category III) accounts for 90-95% of prostatitis cases. However, standard treatment has not yet been established. It is known that polyphenols have an inhibitory effect on inflammation by their antioxidative capacity, and oligonol, a polyphenol derivative, has much higher bioavailability and bioactivity than common polyphenols. We investigated the anti-inflammatory effects and mechanisms of oligonol in estradiol-induced prostatitis rat models. MATERIALS AND METHODS: Prostatitis was induced by 17 beta-estradiol (E2) and dihydrotestosterone (DHT) in Wistar male rats (n = 20). Ten rats were placed in the oligonol-treated group and 10 in the E2 + DHT-treated group. The other 10 rats were also included as normal control group. Oligonol (60 mg/kg/day) was administered via gavage tube for 4 weeks. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and tumor necrosis factor-alpha (TNF-alpha) were quantified, and phosphorylation of IkappaBa and histological changes were also evaluated in prostatic tissue. RESULTS: The SOD and GPx activity showed tendencies to increase in the oligonol-treated group compared to the normal control group. TNF-alpha expression was slightly reduced in the oligonol-treated group. Western blotting demonstrated that phosphorylation of IkappaBa in the oligonol-treated group was significantly lower than in the normal control group. The E2 + DHT-treated group revealed severe atrophy of acinar epithelial cells and infiltration of leukocytes and lymphocytes in the prostate, however, the oligonol-treated group showed overall reduction in inflammatory features. CONCLUSION: This study demonstrates that oligonol improves estradiol-induced non-bacterial prostatitis by regulating phosphorylation of IkappaBa. These findings suggest that oligonol has a beneficial effect on prevention and treatment of CP/CPPS.
Animals ; Blotting, Western ; Body Weight/drug effects ; Estradiol/*adverse effects ; Flavonoids/*therapeutic use ; Immunoassay ; Male ; Phenols/*therapeutic use ; Prostate/drug effects/pathology ; Prostatitis/*chemically induced/metabolism/*prevention & control ; Rats ; Rats, Wistar ; Superoxide Dismutase/metabolism ; Tumor Necrosis Factor-alpha/metabolism