Component Of Benign Prostatic Hyperplasia Research Articles

Development and validation of a clinical nomogram to predict prostatic inflammation in men with lower urinary tract symptoms.

Prostatic inflammation is an important etiological component of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). The Prostatic Inflammation Nomogram Study (PINS) aimed to develop and validate a nomogram for predicting the presence of prostatic inflammation in men with LUTS. This non-interventional, cross-sectional, prospective study was conducted in six secondary/tertiary centers across Cyprus, Greece, Italy, Portugal, and Spain. Men (≥40 years) with BPH/LUTS scheduled to undergo prostatic surgery or transrectal ultrasound-guided (TRUS) prostate biopsy were included. Fifteen demographic and clinical participant characteristics were selected as possible predictors of prostatic inflammation. The presence of inflammation (according to Irani score) in the prostatic tissue samples obtained from surgery/TRUS biopsy was determined. The effect of each characteristic on the likelihood a prostate specimen demonstrated inflammation (classified by Irani score into two categories, 0-2 [no/minimal inflammation] or 3-6 [moderate/severe inflammation]) was assessed using multiple logistic regression. A nomogram was developed and its discriminatory ability and validity were assessed. In total, 423 patients (mean age 68.9 years) were recruited. Prostate volume ultrasound (PVUS) > 50 mL, history of urinary tract infection (UTI) treatment, presence of diabetes, and International Prostate Symptom Score (IPPS) Storage score were statistically significant predictors of Irani classification. Logistic regression demonstrated a statistically significant effect for leucocytes detected via urine dipstick, presence of diabetes, PVUS > 50 mL, history of UTIs, and higher IPSS Storage score for the odds of an inflammatory score category of 3-6 versus 0-2. The nomogram had a concordance index of 0.71, and good internal validity. The nomogram developed from PINS had good predictive ability and identified various characteristics to be predictors of prostatic inflammation. Use of the nomogram may aid in individualizing treatment for LUTS, by identifying individuals who are candidates for therapies targeting prostatic inflammation.

Pathogenetic Effects of Global Stress on the Dynamic Component of Benign Prostatic Hyperplasia in Men in Ukraine

The military situation in Ukraine significantly worsened the quality of medical care for the population. Of all Ukrainian men the age category from 30 to 60 years old who take part in military operations is the most effective one. Another, no less important part of the male population is the old persons, who, as a result of military operations, have limited opportunities to receive medical care. Currently, observing by urologist, required for benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS) due to combat operations in the country, is often performed via distance curation. The doctor needs a clear understanding of the patient’s medical history, taking into account his psychological and somatic status, the use of medicines. Stress negatively affects men’s health, worsening the hormonal background, mental state and aggravating problems of the genital and urinary systems. Psychological stress is a factor in the exacerbation or occurrence of urological complaints, which can lead to the pathological activation of certain parts of the sympathetic nervous and hormonal systems, the development of LUTS by BPH. Tamsulosin is considered to be the most recognized and widely used treatment for LUTS in patients with BPH. The classic medicament approach of BPH monotherapy is the use of Serenoa repens extract. The distance appointment of selective α-adrenoblockers, both in monotherapy and in combinations, is an important measure of providing specialized urological care to the population.

Genetic, Genomic, and Heritable Components of Benign Prostatic Hyperplasia

Genetic, Genomic, and Heritable Components of Benign Prostatic Hyperplasia

Inflammation in the Pathophysiology of Benign Prostatic Hypertrophy

ContextBenign prostatic hyperplasia (BPH) is classically understood to be a disturbance in prostate homeostasis, but the underlying questions of how and why this disturbance occurs have yet to be answered definitively. An increasing body of evidence points to inflammation as a central component of the pathogenic process of BPH. ObjectiveTo review recent evidence regarding the association between histologic prostatic inflammation and the development and progression of BPH. Evidence acquisitionThis article is based primarily on material presented at a satellite symposium entitled, “Inflammation and Prostatic Diseases: From Bench to Bedside,” held during the 2015 annual meeting of the European Association of Urology in Madrid, Spain. Current data regarding the link between inflammation and BPH were reviewed. Evidence synthesisEvidence from a canine model of BPH and human prostate tissue has confirmed the presence of inflammation as a component of BPH. Pronounced inflammation was observed in dogs with hormonally induced prostatic hyperplasia. Longitudinal biopsy indicated that the cell-mediated and humoral immune response was preceded by hyperplasia. In surgically treated human BPH specimens, high-level inflammation was significantly associated with prostate enlargement and symptom evolution. Current opinion is that chronic inflammation and endocrine changes lead to disturbed homeostasis and tissue damage or, alternatively, that abnormal stem cell expansion and disturbed homeostasis lead to chronic inflammation and endocrine changes. Either way, a “vicious cycle” is initiated that leads to hyperplasia with fibrosis and changes in prostate tissue composition. ConclusionsIncreased insight into BPH pathogenesis indicates that restoring tissue endocrine metabolism and reducing chronic inflammation are prostate-specific targets for the treatment of BPH. Patient summaryIncreasing insight into benign prostatic hyperplasia (BPH) pathogenesis indicates that restoring tissue endocrine metabolism and reducing chronic inflammation are prostate-specific targets for treatment of BPH.

788 Different role of T cell on stromal and epithelial components of benign prostatic hyperplasia

788 Different role of T cell on stromal and epithelial components of benign prostatic hyperplasia

Ezetimibe Reduces Enlarged Prostate in an Animal Model of Benign Prostatic Hyperplasia

Benign prostatic hyperplasia is a common urinary tract disorder that affects aging men. The molecular mechanisms underlying benign prostatic hyperplasia are obscure and the development of animal models to test novel treatment strategies is challenging. We report that the Bio 87.20 hamster strain (Bio Breeders, Watertown, Massachusetts) shows 5α-reductase-sensitive prostate enlargement and a decrease in circulating cholesterol reduces prostate size. Bio 87.20 hamsters 17 months old with an enlarged prostate were fed a diet containing no or minimal cholesterol and including finasteride (Merck, Whitehouse Station, New Jersey) and/or ezetimibe (Schering-Plough, Kenilworth, New Jersey) for 4 months. The prostate complex was removed, volume and weight were determined, and tissue was examined histologically. Prostate enlargement depended on cholesterol in the diet. Blockade of intestinal cholesterol transport with ezetimibe induced prostate regression to a similar extent as the 5α-reductase inhibitor finasteride, a compound used to treat benign prostatic hyperplasia in humans. Histological analysis indicated that finasteride induced widespread prostatic atrophy but normal glandular architecture was preserved in the ezetimibe cohort. Results indicate that dysregulation of cholesterol metabolism may be a component of benign prostatic hyperplasia and ezetimibe may be effective as an alternative or adjunct to standard treatment. Our findings also show that the Bio 87.20 hamster is a suitable model for preclinical evaluation of novel benign prostatic hyperplasia therapy.

Androgens regulate adenylate cyclase activity and intracellular calcium in stromal cells derived from human prostate

Increased smooth muscle tone is a significant component of benign prostatic hyperplasia, the onset of which correlates with age and declining serum testosterone levels. This study investigates the effects of androgens on key regulators of smooth muscle tone: intracellular calcium ([Ca(2+)](i)) and cyclic adenosine monophosphate (cAMP) in human cultured prostatic stromal cells (HCPSC). HCPSC were cultured in the absence or presence of dihydrotestosterone (DHT; 3, 30, and 300 nM) or testosterone (0.3-300 nM) alone or in the presence of flutamide (10 microM). Changes in [Ca(2+)](i) were determined in FURA-2AM (10 microM) loaded cells. Changes in cAMP were determined by Alpha Screen(R) assay. Up to 32% of cultured cells exhibited spontaneous elevations of [Ca(2+)](i). The frequency of these elevations was reduced by nifedipine (10 microM), ryanodine (1 microM), and the adenylate cyclase inhibitor MDL 12,330A (20 microM). Compared to steroid-free cells, a 3-day incubation of cells with testosterone (only 3 nM) elevated basal, but not peak [Ca(2+)](i). In the presence of flutamide, all concentrations of testosterone tested elevated basal, but not peak [Ca(2+)](i). DHT (30 and 300, but not 3 nM) lowered peak and basal [Ca(2+)](i). Increased testosterone concentration dependently decreased resting cell cAMP (pIC(50): 7.64 +/- 0.29 nM). These findings demonstrate that some HCPSC have the ability to spontaneously and transiently elevate [Ca(2+)](i). The magnitude of these [Ca(2+)](i) peaks, along with resting levels of calcium and cAMP, appear to be regulated by androgens.

Vitamin D receptor agonists target static, dynamic, and inflammatory components of benign prostatic hyperplasia

The bioactive form of vitamin D, 1,25-dihydroxyvitamin D(3), is a secosteroid hormone that binds to the vitamin D receptor (VDR), a member of the nuclear receptor superfamily, and modulates a variety of biological functions. The VDR is expressed by most cell types, including cells of the urogenital system, such as prostate and bladder cells. In particular, the prostate is a target organ of VDR agonists and represents an extrarenal synthesis site of 1,25-dihydroxyvitamin D(3). We have analyzed the capacity of VDR agonists to treat benign prostatic hyperplasia (BPH), a complex syndrome characterized by a static component related to prostate overgrowth, a dynamic component responsible for urinary irritative symptoms, and an inflammatory component. Data reviewed here demonstrate that VDR agonists, and notably elocalcitol, reduce the static component of BPH by inhibiting the activity of intraprostatic growth factors downstream of the androgen receptor, the dynamic component by targeting the RhoA/ROCK pathway in prostate and bladder cells, and the inflammatory component by targeting the NF-kappaB pathway.

The effects of lovastatin on conventional medical treatment of lower urinary tract symptoms with finasteride

To explore whether or not statins have any impact on the progression of components of benign prostatic hyperplasia (lower urinary tract symptoms severity, prostate volume and serum prostate specific antigen (PSA) when combined with other agents inhibiting growth of prostate cells. This was a preliminary, clinical study. Eligible patients were aged > 50 yrs, with International Prostate Symptom Score (IPSS) between 9 and 19, total prostate volume (TPV) >40 mL, and serum PSA > 1.5 ng/mL. Patients were divided in two groups: those with and those without lipidemia. After selection, eligible BPH patients with lipidemia (n = 18) were prescribed lovastatin 80 mg daily and finasteride 5 mg daily, while eligible patients without lipidemia (n = 15) were prescribed only finasteride 5 mg daily. IPSS, TPV and serum PSA were evaluated at end point (4 months). There was no difference between the two groups on the primary end point of mean change from baseline in IPSS (p = 0.69), TPV (p = 0.90) and PSA (p = 0.16) after 4 months of treatment. Short-term lovastatin treatment does not seem to have any effect on IPSS, TPV and PSA in men with prostatic enlargement due to presumed BPH.

Conservative treatment of benign prostatic hyperplasia

Medical treatment of benign prostatic hyperplasia is reviewed by the author. Experiences with herbal extracts have been known for more than 2 decades. Treating benign prostatic hyperplasia with these extracts is recommended in initial phase. Prostate volume is decreased and mechanical component of dysuria is improved by treating for a long time (months, years) with 5-alpha-reductase finasteride which contains hormone. This drug is indicated when volume of the prostate is over 40 g. Dynamical component of benign prostatic hyperplasia is treated with alpha-receptor blockers which act on the bladder neck. These medicines have effects earlier and are recommended for all patients with benign prostatic hyperplasia independently of prostate volume. These might have some side effects like hypotension. The improving effects of 5-phosphodiesterase inhibitors on BPH have been discovered recently. The same effect has been described of alpha-blockers on sexual activity.

Association of Anthropometric Measures with the Presence and Progression of Benign Prostatic Hyperplasia

The authors investigated the association of anthropometric measures with the presence and progression of components of benign prostatic hyperplasia (BPH) and a clinical outcome of BPH in a cohort of healthy, Caucasian men aged 40-79 years that was randomly selected from the Olmsted County, Minnesota, population beginning in 1990. Exclusionary criteria included prostate or bladder surgery, urethral surgery or stricture, or medical or other neurologic conditions that could affect normal urinary function. Height, weight, and waist and hip circumferences were measured. Components of BPH, including American Urological Association Symptom Index scores, peak urinary flow rate, and prostate volume, were assessed on a randomly selected subsample. Acute urinary retention was assessed through review of community medical records. There were few significant associations of anthropometric measures with the presence or progression of components of BPH or clinical outcome of BPH, and there were no instances where the point estimates for the BPH components suggested a dose-response effect. The authors conclude that anthropometric measures are not significantly associated with the presence or progression of BPH as measured by American Urological Association Symptom Index scores, peak urinary flow rate, prostate volume, or acute urinary retention. These data provide no evidence of a consistent significant relation between anthropometric measures and BPH.

Novel Action of Botulinum Toxin on the Stromal and Epithelial Components of the Prostate Gland

Intraprostatic injection of BTX-A has demonstrated clinical improvement in men with bladder outlet obstruction. We investigated the mechanisms of action of BTX-A on the prostate. Adult male Sprague-Dawley rats were injected with varying doses of BTX-A into the prostate and the prostates were harvested after 1 or 2 weeks. The effects of BTX-A on prostate histology, and the proliferative and apoptotic indexes were determined using hematoxylin and eosin staining, proliferative cell nuclear antigen staining and TUNEL staining, respectively. Changes in alpha(1A) adrenergic receptor and androgen receptor were evaluated by Western blotting. One week after BTX-A injection generalized prostate atrophy was observed. There was a significant increase in apoptotic cells (12, 16 and 22-fold), and decrease in proliferative cells (38%, 77% and 80%) and alpha(1A) adrenergic receptor (13%, 80% and 81%) for 5, 10 and 20 U, respectively. There was no significant change in androgen receptors. The effects were decreased 2 weeks after BTX-A treatment. BTX-A injection into the prostate alters cellular dynamics by inducing apoptosis, inhibiting proliferation and down-regulating alpha(1A) adrenergic receptors. BTX-A may potentially be the drug that has dual actions on the static and dynamic components of benign prostatic hyperplasia.

Uroselectivity in male dogs of silodosin (KMD‐3213), a novel drug for the obstructive component of benign prostatic hyperplasia

Our main aim was to compare the prostatic selectivity of silodosin with that of other alpha(1)-adrenoceptor (AR) antagonists. We examined uroselectivities in two sets of experiments namely, in vitro and in vivo functional studies using male dogs. In the in vitro study, after evaluating the inhibitory effects of silodosin on noradrenaline (NA)-induced contractions in the isolated prostate and isolated carotid artery using the Magnus method, we calculated prostatic selectivity. In the in vivo study, we examined the effects of drugs on the hypogastric nerve stimulation (HNS)-induced increase in intraurethral pressure (IUP) and on blood pressure. The uroselectivity of silodosin was compared with those of tamsulosin and naftopidil. In vitro, all drugs antagonized NA-induced contraction in both prostate and carotid artery. The prostatic selectivity of silodosin (79.4) was much higher than those of tamsulosin (1.78), naftopidil (0.55), BMY 7378 (0.115), and prazosin (0.01). In vivo, intravenously (i.v.) administered silodosin dose-dependently inhibited the HNS-induced increase in IUP with much less hypotensive effect than either tamsulosin or naftopidil, the uroselectivity (ED(15)/ID(50)) of silodosin (237) being significantly higher than those of tamsulosin (1.21) and naftopidil (2.65). Our results clearly demonstrate that silodosin is a potent and highly selective alpha(1A)-AR antagonist. A selective alpha(1A)-AR antagonist such as silodosin may have good potential as a less-hypotensive drug for the treatment of urinary dysfunction in benign prostatic hyperplasia patients.

Pharmacology of tamsulosin: saturation-binding isotherms and competition analysis using cloned alpha 1-adrenergic receptor subtypes.

alpha 1-adrenergic receptors (alpha 1 ARs) are important in the dynamic component of benign prostatic hyperplasia (BPH). Currently, several alpha 1AR antagonists are being used in the treatment of BPH. In order to more fully characterize the pharmacology of the alpha 1AR antagonist tamsulosin, we utilized saturation-binding isotherms with [3H] tamsulosin to determine the Kd of this compound at all three cloned alpha 1AR subtypes stably expressed in rat-1 fibroblasts. To confirm these results, we performed competition binding experiments, displacing [125I]HEAT with increasing concentrations of alfuzosin, doxazosin, 5-methyl-urapidil, prazosin, tamsulosin, terazosin, and (+)YM617 (stereoisomer of tamsulosin) in the same clonal cell lines. [3H]tamsulosin binds to cloned alpha 1AR subtypes with a rank order of affinity of alpha 1a = alpha 1d > alpha 1b. Competition experiments confirmed the relative nonselectivity of alfuzosin, doxazosin, and prazosin, but revealed slight alpha 1b = alpha 1d > alpha 1a selectivity for terazosin, and clear alpha 1a = alpha 1d > alpha 1b for (+)YM617 and tamsulosin([-]YM617); alpha 1a > alpha 1d > alpha 1b selectivity for 5-methyl-urapidil was confirmed. We conclude that tamsulosin displays selectivity for alpha 1a and alpha 1d ARs. This selectivity may contribute to the tamsulosin efficacy reported in several recent clinical studies in patients with BPH.

Pharmacological Characterization of the Isolated Canine Prostate

Purpose The goal of the present study was to characterize the responses of the isolated normal canine prostate to various contracting and relaxing stimuli to determine which pharmacological agents may have utility against the dynamic component of benign prostatic hyperplasia (BPH). Materials and Methods Isometric force development was measured in isolated strips of prostate tissue. Results The alpha-adrenergic agonists were the most efficacious stimulants tested (phenylephrine EC 50 = 2.1 micromolar). Endothelin-1, acting primarily via ET A receptors, was more potent (EC 50 = 27 nM.) but less efficacious. Histamine (EC 50 = 14.7 micromolar), serotonin (EC sub 50 = 0.12 micromolar), carbachol (EC 50 = 5.9 micromolar) and KCl (EC sub 50 = 48.8 mM.) were also less efficacious than phenylephrine. Nifedipine was a potent (IC 50 = 28 nM.) and efficacious (74 percent inhibition) inhibitor of phenylephrine-induced force. Potassium channel activator drugs were also efficacious relaxants, producing approximately 80 percent inhibition of force; rank order of potency was P1075 greater than cromakalim greater than diazoxide. Sodium nitroprusside was a weak relaxant, producing only approximately 40 percent relaxation at a concentration of 100 micromolar. Both isoproterenol and forskolin were effective relaxants (75 to 90 percent relaxation). Conclusions We conclude that potassium channel activators, adenylate cyclase stimulators, or endothelin antagonists may have utility against the dynamic component of outflow obstruction secondary to BPH.

Is one single prostate biopsy helpful for choosing a medical treatment of benign prostatic hyperplasia? a quantitative computerized morphometric study

Objectives Individual differences in proportion of stroma, epithelium and luminal space components in benign prostatic hyperplasia (BPH) may explain the differences in clinical outcome of the patients treated with α-reductase inhibitors or α-blocking agents and other alternative treatments. Knowledge of the individual proportions of these elements may orient the clinician toward different therapeutic approaches. To determine whether a single prostate biopsy is representative of the whole adenoma, using quantitative morphometry, we have compared the percentage of smooth muscle cells and glandular cells in one prostate needle biopsy and in the corresponding prostate adenoma removed by open surgery. Methods Quantification was made using a computerized image analysis system and immunohistochemical staining (actin antiactin for the smooth muscle cells and anti-prostate-specific antigen (PSA) for the epithelial cells) in 14 patients who underwent retropubic prostatectomy. Results Mean percentage of smooth muscle fibers, glandular epithelium, and glandular lumina in the prostate biopsy were, respectively, 34% (range, 20% to 42%, SD 5.9), 29% (range, 13% to 42%, SD 7.2), and 20% (range, 13% to 30%, SD 4.8). In the corresponding prostate adenoma, they were, respectively, 38% (range, 28% to 45%, SD 4.7), 32% (range, 25% to 40%, SD 4.5), and 19% (range, 13% to 34%, SD 6.1). The mean percentages of epithelial or glandular cells in the prostate biopsy and the corresponding adenoma were not statistically different ( P > 0.05), whereas those for the smooth muscle cell percentage were different ( P = 0.02). However, a statistically significant correlation between the whole adenoma and the needle biospy sample was found in the percentage of smooth muscle cells ( P = 0.028). Analyzing the morphometric data in conjunction with the serum PSA level and the volume of the adenoma, we found a statistically significant positive correlation between the volume of the adenoma and the ratio (percentage of epithelial cells/serum PSA level) ( P = 0.009, r = 0.67). Conclusions Major differences are found in the primary tissue composition of different hyperplastic prostates. Computerized histologic quantification of the different components of BPH in the entire adenoma and a needle biopsy demonstrate that a single prostate biopsy is representative of the entire prostate adenoma. Morphometric data from a single biopsy of the prostate adenoma in combination with the serum PSA level and the volume of the prostate adenoma could therefore help to orient medical treatment of BPH by patient selection based on the knowledge of the distribution of the various components of BPH. UROLOGY ® 47: 329–334, 1996.