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British Journal of Pharmacology Sep 2020Smooth muscle contraction in the cardiovascular system, airways, prostate and lower urinary tract is involved in the pathophysiology of many diseases, including... (Review)
Review
Smooth muscle contraction in the cardiovascular system, airways, prostate and lower urinary tract is involved in the pathophysiology of many diseases, including cardiovascular and obstructive lung disease plus lower urinary tract symptoms, which are associated with high prevalence of morbidity and mortality. This prominent clinical role of smooth muscle tone has led to the molecular mechanisms involved being subjected to extensive research. In general smooth muscle contraction is promoted by three major signalling pathways, including the monomeric GTPase RhoA pathway. However, emerging evidence suggests that monomeric GTPases other than RhoA may be involved in signal transduction in smooth muscle contraction, including Rac GTPases, cell division control protein 42 homologue, adenosine ribosylation factor 6, Ras, Rap1b and Rab GTPases. Here, we review these emerging functions of non-RhoA GTPases in smooth muscle contraction, which has now become increasingly more evident and constitutes an emerging and innovative research area of high clinical relevance.
Topics: Humans; Male; Muscle Contraction; Muscle, Smooth; Prostate; Respiratory System; Signal Transduction; rhoA GTP-Binding Protein
PubMed: 32579705
DOI: 10.1111/bph.15172 -
BMC Urology Apr 2019It has been recognized that the incidence of prostatic utricle in boys is increasing and is closely associated with diseases such as hypospadias. However, the clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It has been recognized that the incidence of prostatic utricle in boys is increasing and is closely associated with diseases such as hypospadias. However, the clinical features of prostatic utricle with normal external genitalia have received little attention.
METHODS
Based on this, a series of 22 male children with prostatic utricles has been compiled by adding our 3 patients to 19 cases reported. All children enrolled had normal external genitalia. Clinical data of the case was reviewed.
RESULTS
Urinary tract infection, purulent urethral discharge and pyuria were the most common presenting chief complaint (41%), irritative lower urinary tract symptoms were present in 17% of cases, obstructive lower urinary tract symptoms were noted in 14%. Urinary retention has been reported in 18% and epididymitis has been reported in 14%. Relatively rare clinical symptoms are abdominal pain, hematuria, and hematospermia. A case of calculus formation and a case of neoplasia within the prostatic utricle has been reported. A cystic mass found by digital rectal examination is the most common presenting sign. A utricular lesion posterior to the bladder was revealed by imaging examination. Unilateral renal agenesis was associated in 32% of reports. Non-surgical approach was chosen in 3 cases, transrectal ultrasonography guided aspiration has been reported in 1 case. Endoscopic techniques were used in 3 cases. Open excision was used in 11 cases. The laparoscopic excision was chosen in 3 cases and Robot-assisted laparoscopy was reported in 1 case. Symptoms and signs disappeared after treatment in all children, and no recurrence occurred during follow-up.
CONCLUSIONS
Prostate utricles without external genital anomalies are rarely reported in children, and are easily missed and misdiagnosed, often accompanied by recurrent urinary tract infections, lower urinary tract symptoms, epididymitis, dysuria and other symptoms. Imaging studies can confirm the diagnosis. Symptomatic and large utricles should be actively treated. The treatment program should be based on the age, clinical symptoms, and size and location of the utricle.
Topics: Adolescent; Child; Child, Preschool; Genitalia, Male; Humans; Hypospadias; Infant; Male; Prostate; Urogenital Abnormalities
PubMed: 30943976
DOI: 10.1186/s12894-019-0450-z -
Archives of Pathology & Laboratory... Oct 2014In this article, we review prostatic lymphomas and discuss the differential diagnosis of high-grade malignant neoplasms of the prostate. We illustrate this with a case... (Review)
Review
In this article, we review prostatic lymphomas and discuss the differential diagnosis of high-grade malignant neoplasms of the prostate. We illustrate this with a case of a 46-year-old man seen with lower urinary tract obstruction who had diffuse involvement by a high-grade malignancy on prostate biopsy. Morphologic evaluation and immunohistochemistry were consistent with diffuse large B-cell lymphoma of the prostate. Workup with positron emission tomography-computed tomography demonstrated intensely hypermetabolic lymph nodes in the mediastinum, as well as widespread osseous involvement and involvement of the pancreatic tail, prostate, and urinary bladder, suggesting secondary prostatic involvement by a nodal lymphoma. Lymphomas of the prostate are uncommon in surgical pathology practice and usually represent secondary involvement from leukemia/lymphoma at a more typical site. Chronic lymphocytic leukemia/small lymphocytic lymphoma is the most common subtype.
Topics: Diagnosis, Differential; Dysuria; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Hematuria; Humans; Low Back Pain; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Multimodal Imaging; Neoplasm Grading; Pelvic Pain; Positron-Emission Tomography; Prostate; Prostatic Neoplasms; Tomography, X-Ray Computed; Urethral Obstruction
PubMed: 25268190
DOI: 10.5858/arpa.2014-0276-CC -
Toxins Sep 2019Patients with benign prostatic hyperplasia (BPH) can exhibit various lower urinary tract symptoms (LUTS) owing to bladder outlet obstruction (BOO), prostatic... (Review)
Review
Patients with benign prostatic hyperplasia (BPH) can exhibit various lower urinary tract symptoms (LUTS) owing to bladder outlet obstruction (BOO), prostatic inflammation, and bladder response to BOO. The pathogenesis of BPH involves an imbalance of internal hormones and chronic prostatic inflammation, possibly triggered by prostatic infection, autoimmune responses, neurogenic inflammation, oxidative stress, and autonomic dysfunction. Botulinum toxin A (BoNT-A) is well recognized for its ability to block acetylcholine release at the neuromuscular junction by cleaving synaptosomal-associated proteins. Although current large clinical trials have shown no clinical benefits of BoNT-A for the management of LUTS due to BPH, BoNT-A has demonstrated beneficial effects in certain subsets of BPH patients with LUTS, especially in males with concomitant chronic prostatitis/chronic pelvic pain syndrome and smaller prostate. We conducted a review of published literature in Pubmed, using Botulinum toxin, BPH, BOO, inflammation, LUTS, and prostatitis as the key words. This article reviewed the mechanisms of BPH pathogenesis and anti-inflammatory effects of BoNT-A. The results suggested that to achieve effectiveness, the treatment of BPH with BoNT-A should be tailored according to more detailed clinical information and reliable biomarkers.
Topics: Animals; Anti-Inflammatory Agents; Botulinum Toxins, Type A; Humans; Lower Urinary Tract Symptoms; Male; Neuromuscular Agents; Prostatic Hyperplasia; Prostatitis
PubMed: 31546892
DOI: 10.3390/toxins11090547 -
International Urology and Nephrology Jul 2015High prevalence of lower urinary tract symptoms (LUTS) consistent with benign prostate hyperplasia (BPH) is associated with obesity and prostatic inflammation. Here, we...
OBJECTIVES
High prevalence of lower urinary tract symptoms (LUTS) consistent with benign prostate hyperplasia (BPH) is associated with obesity and prostatic inflammation. Here, we investigated whether chemokines associated with obesity and prostatic inflammation can be measured in normally voided urine of BPH/LUTS patients to demonstrate the mechanistic association between obesity and BPH/LUTS.
METHODS
Frozen urine specimens of BPH/LUTS patients enrolled in the Nashville Men's Health Study were sent for blinded analysis to University of Pittsburgh. Thirty patients were blocked by their AUA-SI (>7 or ≤7) and prostatic enlargement (<40, 40-60, >60 cc). Clinical parameters including age, prostate size, and medications were derived from chart review. CXC chemokines (CXCL-1, CXCL-8, and CXCL-10), CC chemokines (CCL2 and CCL3), and sIL-1ra were measured in thawed urine using Luminex™ xMAP(®) technology and ELISA for NGF.
RESULTS
Urinary CCL2 levels were several fold higher compared with the other six proteins, of which CCL3 was detectable in less than one-fourth of patients. Urine levels of sIL-1ra and CXCL-8 were significantly associated with increasing BMI and waist circumference in BPH patients. CXCL-8 showed a marginal association with overall AUA-SI scores, as well as obstructive (p = 0.08) symptom subscores. Prostate volume was inversely and marginally associated with urinary CXCL-10 (p = 0.09).
CONCLUSIONS
Urine levels of CXCL-8, CXCL-10, and sIL-1ra were associated with varying degrees with LUTS severity, prostate size, and obesity, respectively. These findings in urine are consistent with past studies of chemokine levels from expressed prostatic secretions and demonstrate the potential of noninvasively measured chemokine in urine to objectively classify BPH/LUTS patients.
Topics: Adult; Chemokine CXCL10; Humans; Inflammation; Interleukin-8; Lower Urinary Tract Symptoms; Male; Middle Aged; Obesity; Prostate; Prostatic Hyperplasia; Statistics as Topic; Urine Specimen Collection
PubMed: 25924782
DOI: 10.1007/s11255-015-0992-2 -
Biological & Pharmaceutical Bulletin Aug 2006Benign prostate hyperplasia (BPH) is common among above 50 years age group, interfere with normal activities of lower urinary tract function and reduce the sense of well... (Review)
Review
Benign prostate hyperplasia (BPH) is common among above 50 years age group, interfere with normal activities of lower urinary tract function and reduce the sense of well being. It can also be progressive, with a lost of urinary retention, bladder infection, bladder calculus and renal failure. Although many men with mild to moderate symptoms to well without therapy, others have gradually increasing symptoms and require medical therapy or surgery. BPH is the non-malignant, uncontrolled growth of cells in the prostate gland. This cell growth usually occurs in the tissue that surrounds the urethra as it passes through the prostate gland to the bladder. As BPH progresses, the gland constricts the urethra and obstructs the urine outflow. The bladder no longer empties completely, creating an environment in which infections, bladder stones, and chronic prostatities may develop. If left untreated, chronic obstruction can lead to the back up of urine into the ureters and compromise kidney function. In hyperplastic prostate tissue, the prostate capsule, and the bladder neck are blocked, by using alpha-adrenergic antagonist drugs; the smooth muscle tone of these structures is decreased. As a result, resistance to urinary flow through the bladder neck and the prostatic urethra decreases and urinary flow increases. A variety of alpha-adrenergic antagonists with distinct properties have been investigated as possible treatments for benign prostate hyperplasia.
Topics: Adrenergic alpha-Antagonists; Humans; Male; Practice Patterns, Physicians'; Prostatic Hyperplasia
PubMed: 16880603
DOI: 10.1248/bpb.29.1554 -
Cell Communication and Signaling : CCS Jul 2021The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of... (Review)
Review
The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease. Video abstract.
Topics: Adrenergic beta-Antagonists; Epithelial-Mesenchymal Transition; Humans; Male; Prostate; Receptors, Adrenergic, alpha-1; Receptors, Adrenergic, beta-1; Signal Transduction; Tumor Microenvironment; Urinary Tract; Urologic Diseases; Urologic Neoplasms
PubMed: 34284799
DOI: 10.1186/s12964-021-00755-6 -
Medical Archives (Sarajevo, Bosnia and... Apr 2019To determine the discriminatory power of penile urethral compression-release index (PCRI), clinical prostate score (CLIPS) and bladder outlet obstruction index 2 (BOON2)...
Penile Compression Release Index Revisited: Evaluation and Comparison with Other Noninvasive Tools in the Prediction of Bladder Outlet Obstruction in Men with Benign Prostatic Enlargement.
AIM
To determine the discriminatory power of penile urethral compression-release index (PCRI), clinical prostate score (CLIPS) and bladder outlet obstruction index 2 (BOON2) for the detection of bladder outlet obstruction (BOO), and the associated bladder abnormality in patients with benign prostatic enlargement (BPE).
MATERIAL AND METHODS
In study was included of 135 patients with proven BPE underwent urodynamic measurement (UDM) and PCR maneuver. PCR Index was calculated following the formula: (Qs-Qss)/Qss x 100(%). CLIPS score was calculated based on non-invasive variables (prostate volume, maximal urinary flow, residual urine and voided volume), while BOON2 was calculated using the formula intravesical prostate protrusion (IPP)-3 x Qmax-0.2 x mean voided volume. UDM results were plotted on Schaefer and URA nomograms.
RESULTS
A comparative analysis was made using ROC curves. The area under the curve (AUC) for PCRI is 0.85 (PTP 91.3%), while AUC for CLIPS and BOON2 is 0.8 (PTP 77.6%) and 0.82 (PTP 74.5%), respectively. PCRI with the cut-off point of 96% clearly distinguishes obstructed patients with normocontractile detrusor and the presence of detrusor overactivity (DO), versus those unobstructed. CLIPS (>10) shows good BOO prediction, but without the possibility of distinguishing between detrusor contractility grade and the occurrence of DO. BOON2 has shown that impaired contractility has influence on this number in obstructed patients.
CONCLUSION
PCRI is a very good noninvasive urodynamic test for a group-wise detection of BOO in patients with BPE and associated bladder co-morbidities; it is therefore superior in comparison with to CLIPS or BOON2.
Topics: Aged; Aged, 80 and over; Diagnostic Techniques, Urological; Humans; Male; Middle Aged; Organ Size; Penis; Prostate; Prostatic Hyperplasia; Risk Assessment; Urethra; Urinary Bladder Neck Obstruction; Urodynamics
PubMed: 31391692
DOI: 10.5455/medarh.2019.73.81-86 -
Journal of Endourology Jan 2023The evidence for prostatic urethral lift (PUL), in treating lower urinary tract symptoms/benign prostatic hyperplasia (BPH) in men with obstructive median lobes (OMLs),... (Randomized Controlled Trial)
Randomized Controlled Trial
The evidence for prostatic urethral lift (PUL), in treating lower urinary tract symptoms/benign prostatic hyperplasia (BPH) in men with obstructive median lobes (OMLs), has grown. In this study, we present the first detailed comparison of outcomes between OML patients treated with PUL in controlled and real-world settings to relevant comparators (subjects treated with transurethral resection of the prostate [TURP] and sham in randomized controlled trials [RCTs]) to demonstrate similar symptom, safety, and patient experience outcomes. Symptom and safety outcomes and patient satisfaction were compared through 12 months among controlled PUL studies: BPH6 RCT (35 men randomized to TURP); L.I.F.T. pivotal RCT in subjects with lateral lobe obstruction (66 subjects randomized to sham) and MedLift, an U.S. Food and Drug Administration-approved Investigational Device Exemption (IDE) extension of the L.I.F.T. trial (45 men with OML). Symptom improvement, catheterization, and adverse event rates were compared between MedLift subjects and OML patients ( = 187) from the large real-world retrospective (RWR) study of PUL filtered on baseline characteristics to approximate the MedLift population. Posttreatment, International Prostate Symptoms Score (IPSS) improvement for MedLift subjects was 170% greater compared with sham at 3 months with significantly better quality of life (QoL), Qmax, and benign prostatic hyperplasia impact index (BPHII). Compared with TURP, MedLift IPSS and QoL improved significantly better at 1 and 3 months and with superior ejaculatory function scores at all time points after PUL. IPSS, QoL, postvoid residual (PVR), and Qmax outcomes were equivalent between MedLift and RWR OML groups at 3, 6, and 12 months. RWR OML patients did not experience higher rates of overall adverse events compared with MedLift. Controlled and real-world outcomes confirm PUL is a safe and effective treatment for BPH patients with and without OML.
Topics: Humans; Male; Lower Urinary Tract Symptoms; Prostate; Prostatic Hyperplasia; Quality of Life; Transurethral Resection of Prostate; Treatment Outcome; Urethra
PubMed: 35876440
DOI: 10.1089/end.2022.0324 -
Central European Journal of Urology 2011To predict bladder outlet obstruction with parameters of non-invasive investigations for patients with symptomatic benign prostatic hyperplasia.
OBJECTIVES
To predict bladder outlet obstruction with parameters of non-invasive investigations for patients with symptomatic benign prostatic hyperplasia.
PATIENTS AND METHODS
A sample of 122 men with moderate to severe lower urinary tract symptoms suggestive of benign prostatic hyperplasia was selected. Transrectal prostate ultrasound, free flow measurement, and transabdominal ultrasound for residual urine were carried out together with digital rectal examination for all patients. All patients underwent urodynamic pressure/flow test. Two groups of obstructed (91 patient) and equivocal/unobstructed (31 patient) were analyzed. Probabilistic model based on logistic regression was developed for prediction of obstruction.
RESULTS
Various parameters were compared in obstructed and non-obstructed/equivocal groups, highlighting important parameters for obstruction. Correlation analysis indicates higher obstruction dependence on average and peak flow rates and lower dependence on total prostate and transition zone volumes, transition zone index. Binary logistic regression model suggests that average flow rate combined with total prostate volume is the best predictor of obstruction (83% of correct predictions; PPV = 92%; NPV = 52%) in the analyzed sample. The analyzed model suggests that peak flow rate could also be almost equally important parameter instead of average flow rate.
CONCLUSIONS
The study suggests that average/peak flow rate combined with total prostate volume can be used for prediction of obstruction. The developed probabilistic model helps to determine patients who need invasive urodynamic testing for decision on surgical treatment.
PubMed: 24578868
DOI: 10.5173/ceju.2011.02.art5