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1.
Biol Direct ; 19(1): 61, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095835

ABSTRACT

Myofibroblast buildup and prostatic fibrosis play a crucial role in the development of benign prostatic hyperplasia (BPH). Treatments specifically targeting myofibroblasts could be a promising approach for treating BPH. Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, holds the potential to intervene in this biological process. This study employs prostatic stromal fibroblasts to induce myofibroblast differentiation through TGFß1 stimulation. As a result, tadalafil significantly inhibited prostatic stromal fibroblast proliferation and fibrosis process, compared to the control group. Furthermore, our transcriptome sequencing results revealed that tadalafil inhibited FGF9 secretion and simultaneously improved miR-3126-3p expression via TGFß1 suppression. Overall, TGFß1 can trigger pro-fibrotic signaling through miR-3126-3p in the prostatic stroma, and the use of tadalafil can inhibit this process.


Subject(s)
Fibroblast Growth Factor 9 , Fibrosis , MicroRNAs , Phosphodiesterase 5 Inhibitors , Prostatic Hyperplasia , Tadalafil , Male , Prostatic Hyperplasia/metabolism , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Tadalafil/pharmacology , Phosphodiesterase 5 Inhibitors/pharmacology , Humans , Fibroblast Growth Factor 9/metabolism , Fibroblast Growth Factor 9/genetics , Prostate/drug effects , Prostate/metabolism , Myofibroblasts/metabolism , Myofibroblasts/drug effects , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Cell Proliferation/drug effects
2.
World J Urol ; 42(1): 427, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39037497

ABSTRACT

PURPOSE: The study aimed to determine the typical clearance and volume of distribution values of tamsulosin in patients with benign prostatic hyperplasia (BPH), and to identify factors with a measurable impact on the drug's elimination. METHODS: This open-label, single-arm population pharmacokinetic study involved 65 adult men with BPH who had been on tamsulosin therapy for at least seven days. The steady-state serum concentrations of tamsulosin were measured using liquid chromatography-tandem quadrupole mass spectrometry. Population pharmacokinetic parameters, their variability, and influencing factors were estimated based on a two-compartment pharmacokinetic model using NONMEM software. RESULTS: The estimated tamsulosin clearance in BPH patients was 0.719 L/h, and the steady-state volume of distribution was 32 L. Neither renal nor liver function parameters had a statistically significant effect on tamsulosin clearance. However, a positive correlation was observed between hemoglobin levels and tamsulosin clearance in the BPH patient cohort. CONCLUSION: Our investigation reveals significant associations between tamsulosin pharmacokinetics and specific characteristics of patients with lower urinary tract symptoms (LUTS) due to BPH. The study highlights that tamsulosin clearance is associated with hemoglobin levels in patients with LUTS/BPH. This study underscores the importance of considering patient-specific factors when managing BPH treatment with tamsulosin, emphasizing associations rather than causative relationships.


Subject(s)
Prostatic Hyperplasia , Tamsulosin , Humans , Prostatic Hyperplasia/drug therapy , Male , Tamsulosin/pharmacokinetics , Tamsulosin/therapeutic use , Aged , Middle Aged , Adrenergic alpha-1 Receptor Antagonists/pharmacokinetics , Adrenergic alpha-1 Receptor Antagonists/therapeutic use , Aged, 80 and over , Lower Urinary Tract Symptoms/drug therapy , Lower Urinary Tract Symptoms/etiology
5.
Nutrients ; 16(14)2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39064710

ABSTRACT

Ageratum conyzoides, an annual herbaceous plant that inhabits tropical and subtropical regions, has been traditionally used in Asia, Africa, and South America for phytotherapy to treat infectious and inflammatory conditions. However, the pharmacological effects of standardized ethanolic extract of Ageratum conyzoides (ACE) on benign prostatic hyperplasia (BPH) remain unexplored. The objective of this research is to examine the potential physiological impacts of ACE, a traditionally utilized remedy for inflammatory ailments, in a rat model with BPH induced by testosterone propionate (TP). Rats were subcutaneously administered TP (3 mg/kg) to induce BPH and concurrently orally administered ACE (20, 50, and 100 mg/kg) daily for 42 days. ACE markedly improved BPH characteristics, including prostate weight, prostate index, and epithelial thickness, while also suppressing androgens and related hormones. The findings were supported by a decrease in androgen receptor and downstream signals associated with BPH in the prostate tissues of the ACE groups. Furthermore, increased apoptotic signals were observed in the prostate tissue of the ACE groups, along with heightened detection of the apoptotic nucleus compared to the BPH alone group. These changes seen in the group that received finasteride were similar to those observed in this group. These findings suggest that ACE shows promise as an alternative phytotherapeutic agent for treating BPH.


Subject(s)
Ageratum , Apoptosis , Cell Proliferation , Plant Extracts , Prostate , Prostatic Hyperplasia , Rats, Sprague-Dawley , Male , Animals , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/chemically induced , Prostatic Hyperplasia/pathology , Plant Extracts/pharmacology , Apoptosis/drug effects , Prostate/drug effects , Prostate/pathology , Rats , Ageratum/chemistry , Cell Proliferation/drug effects , Testosterone/blood , Testosterone Propionate , Disease Models, Animal , Inflammation/drug therapy , Phytotherapy
6.
Age Ageing ; 53(7)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39046116

ABSTRACT

BACKGROUND: Recent studies suggest that 5α-reductase inhibitors (5ARIs) for benign prostate hyperplasia (BPH) result in abnormal retinal anatomical alteration. OBJECTIVE: To compare age-related macular degeneration (AMD) incidence in BPH patients receiving 5ARIs or tamsulosin. DESIGN: Retrospective, population-based cohort study using new-user and active-comparator design. SETTING: General population. SUBJECTS: Males with BPH, newly receiving 5ARIs or tamsulosin from 2010 to 2018. METHODS: Data were extracted from Taiwan's National Health Insurance Research Database. We used Cox proportional hazards model with 1:4 propensity score (PS) matching, based on intention-to-treat analysis to determine the risk of incident AMD. Sensitivity analyses included an as-treated approach and weighting-based PS methods. We also separately reported the risks of incident AMD in patients receiving finasteride and dutasteride to determine risk differences among different 5ARIs. RESULTS: We included 13 586 5ARIs users (mean age: 69 years) and 54 344 tamsulosin users (mean age: 68.37 years). After a mean follow-up of 3.7 years, no differences were observed in the risk of incident AMD between 5ARIs and tamsulosin users [hazard ratio (HR): 1.06; 95% confidence intervals (95% CI): 0.98-1.15], with similar results from sensitivity analyses. However, increased risk of incident age-related macular degeneration was observed in patients receiving dutasteride [HR: 1.13; 95% CI: 1.02-1.25], but not in those receiving finasteride [HR: 0.99; 95% CI: 0.87-1.12], in the subgroup analyses. CONCLUSIONS: We found no difference between 5ARIs and tamsulosin regarding the incidence of AMD in BPH patients. However, the risk profiles for AMD differed slightly between dutasteride and finasteride, suggesting that the potency of androgen inhibition is a factor related to AMD incidence.


Subject(s)
5-alpha Reductase Inhibitors , Dutasteride , Finasteride , Macular Degeneration , Prostatic Hyperplasia , Tamsulosin , Humans , 5-alpha Reductase Inhibitors/adverse effects , 5-alpha Reductase Inhibitors/therapeutic use , Male , Aged , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/epidemiology , Retrospective Studies , Taiwan/epidemiology , Incidence , Macular Degeneration/epidemiology , Macular Degeneration/diagnosis , Macular Degeneration/chemically induced , Dutasteride/therapeutic use , Dutasteride/adverse effects , Tamsulosin/therapeutic use , Tamsulosin/adverse effects , Finasteride/adverse effects , Finasteride/therapeutic use , Risk Factors , Middle Aged , Risk Assessment , Databases, Factual
7.
J Tradit Chin Med ; 44(4): 694-702, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39066530

ABSTRACT

OBJECTIVE: To determine the therapeutic effects of the Zhuangyao Jianshen pill (, ZYJSP) against benign prostatic hyperplasia (BPH) and investigate the underlying mechanism. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into six groups: Control group, BPH model group, finasteride-treated group, ZYJSP low, medium and high dose groups. Except for the control group, 40 rats were castrated and injected with testosterone propionate (TP) for 28 consecutive day to induce BPH. Meanwhile, the corresponding drugs were administered by gavage. The prostate wet weight, prostate index (PI), and the histopathological changes in the prostate were measured as the basis for examining the efficacy of ZYJSP against BPH. Levels of the serum sex hormones, oxidative stress markers, inflammatory markers, renal function markers, growth factors, and Cyclin D1 expression in prostate were measured to characterize the therapeutic mechanism of ZYJSP against BPH. RESULTS: ZYJSP administration significantly reduced prostate wet weight and PI and ameliorated histological changes of the prostate in TP-treated castrated rats. TP markedly increased the levels of creatinine, blood urea nitrogen and growth factors in the serum as well as the expression of the Cyclin D1 in the prostate. Most of these markers were significantly decreased by ZYJSP. ZYJSP significantly restored the dysregulation of testosterone, estradiol, and dihydrotestosterone caused by TP. Furthermore, ZYJSP relieved TP-induced prostate injury and exhibited both anti-inflammatory and anti-oxidant activity by decreasing interleukin-6, interleukin-8, and malondialdehyde levels and increasing the activity of superoxide dismutase in the serum. CONCLUSION: These findings indicate that ZYJSP can effectively ameliorate BPH induced by TP in castrated rats, and the underlying mechanism might be related to regulating sex hormone balance, reducing oxidative stress, and inhibiting the inflammatory response.


Subject(s)
Drugs, Chinese Herbal , Prostatic Hyperplasia , Rats, Sprague-Dawley , Testosterone , Animals , Male , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/chemically induced , Drugs, Chinese Herbal/administration & dosage , Rats , Testosterone/blood , Humans , Oxidative Stress/drug effects , Prostate/drug effects , Prostate/metabolism , Prostate/pathology
8.
Chin J Nat Med ; 22(7): 599-607, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39059829

ABSTRACT

Panax ginseng (C.A. Mey.) has been traditionally employed in Korea and China to alleviate fatigue and digestive disorders. In particular, Korean red ginseng (KRG), derived from streamed and dried P. ginseng, is known for its anti-aging and anti-inflammatory properties. However, its effects on benign prostatic hyperplasia (BPH), a representative aging-related disease, and the underlying mechanisms remain unclear. This study aims to elucidate the therapeutic effects of KRG on BPH, with a particular focus on mitochondrial dynamics, including fission and fusion processes. The effects of KRG on cell proliferation, apoptosis, and mitochondrial dynamics and morphology were evaluated in a rat model of testosterone propionate (TP)-induced BPH and TP-treated LNCaP cells, with mdivi-1 as a control. The results revealed that KRG treatment reduced the levels of androgen receptors (AR) and prostate-specific antigens in the BPH group. KRG inhibited cell proliferation by downregulating cyclin D and proliferating cell nuclear antigen (PCNA) levels, and it promoted apoptosis by increasing the ratio of B-cell lymphoma protein 2 (Bcl-2)-associated X protein (Bax) to Bcl-2 expression. Notably, KRG treatment enhanced the phosphorylation of dynamin-related protein 1 (DRP-1, serine 637) compared with that in the BPH group, which inhibited mitochondrial fission and led to mitochondrial elongation. This modulation of mitochondrial dynamics was associated with decreased cell proliferation and increased apoptosis. By dysregulating AR signaling and inhibiting mitochondrial fission through enhanced DRP-1 (ser637) phosphorylation, KRG effectively reduced cell proliferation and induced apoptosis. These findings suggest that KRG's regulation of mitochondrial dynamics offers a promising clinical approach for the treatment of BPH.


Subject(s)
Apoptosis , Cell Proliferation , Dynamins , Mitochondrial Dynamics , Panax , Prostatic Hyperplasia , Receptors, Androgen , Signal Transduction , Animals , Humans , Male , Rats , Apoptosis/drug effects , Cell Proliferation/drug effects , Dynamins/metabolism , Mitochondrial Dynamics/drug effects , Panax/chemistry , Plant Extracts/pharmacology , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/metabolism , Rats, Sprague-Dawley , Receptors, Androgen/metabolism , Signal Transduction/drug effects
9.
Carbohydr Polym ; 340: 122316, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38858029

ABSTRACT

Epimedium, a traditional Chinese medicine commonly used as a dietary supplement, contains polysaccharides and flavonoids as its main bioactive ingredients. In this study, a neutral homogeneous polysaccharide (EPSN-1) was isolated from Epimedium brevicornu Maxim. EPSN-1 was identified as a glucan with a backbone of →4)-α-D-Glcp-(1→, branched units comprised α-D-Glcp-(1→6)-α-D-Glcp-(1→, ß-D-Glcp-(1→6)-ß-D-Glcp-(1→ and α-D-Glcp-(1→ connected to the C6 position of backbone. The conformation of EPSN-1 in aqueous solution indicated its potential to form nanoparticles. This paper aims to investigate the carrier and pharmacodynamic activity of EPSN-1. The findings demonstrated that, on the one hand, EPSN-1, as a functional ingredient, may load Icariin (ICA) through non-covalent interactions, improving its biopharmaceutical properties such as solubility and stability, thereby improving its intestinal absorption. Additionally, as an effective ingredient, EPSN-1 could help maintain the balance of the intestinal environment by increasing the abundance of Parabacteroides, Lachnospiraceae UGG-001, Anaeroplasma, and Eubacterium xylanophilum group, while decreasing the abundance of Allobaculum, Blautia, and Adlercreutzia. Overall, this dual action of EPSN-1 sheds light on the potential applications of natural polysaccharides, highlighting their dual role as carriers and contributors to biological activity.


Subject(s)
Epimedium , Flavonoids , Glucans , Prostatic Hyperplasia , Epimedium/chemistry , Male , Glucans/chemistry , Glucans/pharmacology , Glucans/isolation & purification , Prostatic Hyperplasia/drug therapy , Flavonoids/chemistry , Flavonoids/pharmacology , Flavonoids/isolation & purification , Animals , Drug Carriers/chemistry , Humans , Gastrointestinal Microbiome/drug effects
10.
J Assoc Physicians India ; 72(4): 21-23, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38881078

ABSTRACT

BACKGROUND: The isometric handgrip (IHG) test is commonly used to detect sympathetic autonomic dysfunction. Tamsulosin, approved for the management of symptomatic benign prostatic hyperplasia (BPH), acts as an antagonist for α1-adrenergic receptors (α1-AR), whereas prazosin, an α1 receptor blocker, being less selective than tamsulosin, is used as an antihypertensive agent clinically. Our objective was to investigate if there is a distinction in blood pressure (BP) increase during IHG exercise between individuals with essential hypertension taking tamsulosin compared to those taking prazosin. MATERIALS AND METHODS: A cross-sectional observational study was performed on 50 subjects receiving tablet prazosin and 47 subjects receiving tamsulosin, who were asked to undergo an IHG test. Pre- and posttest BP was recorded for both the groups, and the difference in diastolic BP (DBP) (delta DBP) was compared between the groups and to their respective baseline values. RESULTS: Post-IHG test, mean DBP was found to be 93.98 ± 9.13 mm Hg in the prazosin group and 101.00 ± 12.05 mm Hg in the tamsulosin group, respectively. The change of delta DBP in the tamsulosin group was significant, but the prazosin group showed an insignificant rise in DBP. CONCLUSION: Prazosin, being less selective than tamsulosin in terms of α1 receptor antagonism, showed suppression of BP during IHG. Tamsulosin demonstrates high selectivity for prostatic receptors while showing minimal affinity for vascular receptors. As a result, its impact on BP is expected to be minimal.


Subject(s)
Adrenergic alpha-1 Receptor Antagonists , Blood Pressure , Hand Strength , Hypertension , Prazosin , Prostatic Hyperplasia , Tamsulosin , Humans , Male , Cross-Sectional Studies , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/physiopathology , Prazosin/pharmacology , Prazosin/therapeutic use , Prazosin/administration & dosage , Tamsulosin/therapeutic use , Middle Aged , Adrenergic alpha-1 Receptor Antagonists/therapeutic use , Adrenergic alpha-1 Receptor Antagonists/pharmacology , Blood Pressure/drug effects , Hypertension/drug therapy , Hypertension/physiopathology , Hand Strength/physiology , Aged , Antihypertensive Agents/therapeutic use , India
11.
Expert Opin Pharmacother ; 25(7): 907-914, 2024 May.
Article in English | MEDLINE | ID: mdl-38828638

ABSTRACT

INTRODUCTION: Benign Prostate Hyperplasia (BPH) significantly impacts men's health and quality of life, with its prevalence rising with age. This review critically examines the cost-effectiveness of pharmacological interventions for BPH to optimize patient outcomes and healthcare resource utilization. AREAS COVERED: This review explores the integration of cost-effectiveness analysis (CEA) into clinical practice, balancing clinical efficacy with economic efficiency in BPH management. We performed a critical literature search, including recent studies on the economic evaluation of BPH treatments, focusing on pharmacotherapies such as alpha-blockers and 5-alpha reductase inhibitors. Additionally, we discussed the concept of CEA and evaluated the role of medicinal reconciliation and the avoidance of polypharmacy in favor of optimal BPH treatment. EXPERT OPINION: Cost-effectiveness analysis is crucial for evaluating BPH treatments, with evidence suggesting a shift towards surgical interventions may offer greater long-term economic benefits. However, these models must be applied cautiously, considering clinical evidence and patient preferences to ensure equitable and patient-centric healthcare.


Subject(s)
5-alpha Reductase Inhibitors , Adrenergic alpha-Antagonists , Cost-Benefit Analysis , Prostatic Hyperplasia , Quality of Life , Humans , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/economics , Male , 5-alpha Reductase Inhibitors/therapeutic use , 5-alpha Reductase Inhibitors/economics , Adrenergic alpha-Antagonists/therapeutic use , Adrenergic alpha-Antagonists/economics , Patient Preference , Cost-Effectiveness Analysis
12.
J Pharm Biomed Anal ; 248: 116264, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38889577

ABSTRACT

Anemarrhena asphodeloides Bunge-Phellodendron chinense Schneid (AAPC) is one of the most widely accepted herb pairs in Chinese medicine prescription for treating benign prostatic hyperplasia (BPH). However, the mechanisms underlying the combination of the two herbs for anti-BPH are still not completely clear. To uncover the potential mechanism of the AAPC herb pair in the treatment of BPH, chemical profiling, network pharmacology, serum metabonomics and experimental validation were integrated. UHPLC-Q-Exactive Orbitrap-MS was performed to characterize the chemical profiling of the herb pair extract, and network pharmacology was employed to forecast the potential effective components, core targets and key signaling pathways. Then, western blot and RT-PCR experiments were conducted to verify the PI3K/Akt/NF-κB signaling pathway predicted by network pharmacology. Finally, the serum differential metabolites and metabolic pathways were analyzed by serum non-targeted metabonomics, and these results were jointly analyzed by MetScape. 51 chemical components of the AAPC herb pair extract were identified, including phellodendrine, magnoflorine, berberine, mangiferin, anemarsaponin BIII, etc. In network pharmacology, the predicted core targets of these components include AKT1, TNF, EGFR, PTGS2, PIK3CA, etc. The KEGG pathway enrichment analysis indicated that PI3K-Akt, Rap1 and MAPK signaling pathways may play a key role in the AAPC herb pair for the treatment of BPH, and the results of animal experiments demonstrated that the herb pair could significantly inhibit the activation and expression of p-PI3K/PI3K, p-Akt/Akt, p-NF-κB/NF-κB in protein and mRNA levels. Furthermore, 31 serum differential metabolites and three main metabolic pathways were obtained by serum non-targeted metabonomics. And the crucial metabolic pathway of arachidonic acid (AA) was obtained by integrated analysis of network pharmacology and metabonomics results. In conclusion, the AAPC herb pair can improve BPH through inhibiting the activation and expression of the PI3K/Akt/NF-κB signaling pathway and AA metabolism.


Subject(s)
Anemarrhena , Drugs, Chinese Herbal , Metabolomics , Network Pharmacology , Phellodendron , Prostatic Hyperplasia , Signal Transduction , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/blood , Male , Anemarrhena/chemistry , Metabolomics/methods , Network Pharmacology/methods , Phellodendron/chemistry , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Signal Transduction/drug effects , Chromatography, High Pressure Liquid/methods , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Plant Extracts/pharmacology
13.
World J Urol ; 42(1): 365, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822877

ABSTRACT

AIM: This study aims to evaluate the effectiveness and safety of administering double-dose tamsulosin (0.8 mg) for treating patients with benign prostatic hyperplasia (BPH) who have not responded to the standard single dose of tamsulosin (0.4 mg) and are deemed unsuitable for transurethral resection (TUR) intervention. MATERIALS AND METHODS: Between November 2022 and July 2023, we prospectively analyzed 111 patients who were experiencing severe BPH symptoms. These patients received a double dose of tamsulosin for one month. We collected baseline characteristics such as age, body mass index, and underlying medical conditions. Various parameters including the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, prostate volume, peak urinary flow rate (Qmax), voided volume, and post-void residual volume were evaluated before and after treatment. RESULTS: All 111 patients completed the study. The mean age, PSA level, and prostate volume were 63.12 ± 4.83 years, 3.42 ± 0.93 ng/ml, and 50.37 ± 19.23 ml, respectively. Of these patients, 93 showed improvement in Qmax, post-void residual volume, and IPSS score (p-value = 0.001). The total IPSS score and total Qmax improved from 24.03 ± 2.49 and 7.72 ± 1.64 ml/sec to 16.41 ± 3.84 and 12.08 ± 2.37 ml/sec, respectively. CONCLUSION: Double-dose 0.8mg tamsulosin as an alpha-blocker therapy appears to be a viable temporary management option for BPH patients who have not responded to the standard single dose 0.4mg tamsulosin and are not suitable candidates for TUR intervention.


Subject(s)
Adrenergic alpha-1 Receptor Antagonists , Prostatic Hyperplasia , Tamsulosin , Humans , Tamsulosin/administration & dosage , Tamsulosin/therapeutic use , Male , Prostatic Hyperplasia/surgery , Prostatic Hyperplasia/drug therapy , Middle Aged , Aged , Prospective Studies , Adrenergic alpha-1 Receptor Antagonists/administration & dosage , Adrenergic alpha-1 Receptor Antagonists/therapeutic use , Treatment Failure , Treatment Outcome , Drug Administration Schedule
15.
Neurology ; 103(2): e209570, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38896813

ABSTRACT

BACKGROUND AND OBJECTIVES: Terazosin, doxazosin, and alfuzosin (Tz/Dz/Az) are α-1 adrenergic receptor antagonists that also bind to and activate a key adenosine triphosphate (ATP)-producing enzyme in glycolysis. It is hypothesized that the increase in energy availability in the brain may slow or prevent neurodegeneration, potentially by reducing the accumulation of alpha-synuclein. Recent work has suggested a potentially neuroprotective effect of the use of Tz/Dz/Az in Parkinson disease in both animal and human studies. We investigated the neuroprotective effects of Tz/Dz/Az in a closely related disease, dementia with Lewy bodies (DLB). METHODS: We used a new-user active comparator design in the Merative Marketscan database to identify men with no history of DLB who were newly started on Tz/Dz/Az or 2 comparator medications. Our comparator medications were other drugs commonly used to treat benign prostatic hyperplasia that do not increase ATP: the α-1 adrenergic receptor antagonist tamsulosin or 5α-reductase inhibitor (5ARI). We matched the cohorts on propensity scores and duration of follow-up. We followed up the matched cohorts forward to estimate the hazard of developing DLB using Cox proportional hazards regression. RESULTS: Men who were newly started on Tz/Dz/Az had a lower hazard of developing DLB than matched men taking tamsulosin (n = 242,716, 728,256 person-years, hazard ratio [HR] 0.60, 95% CI 0.50-0.71) or 5ARI (n = 130,872, 399,316 person-years, HR 0.73, 95% CI 0.57-0.93). while the hazard in men taking tamsulosin was similar to that of men taking 5ARI (n = 159,596, 482,280 person-years, HR 1.17, 95% CI 0.96-1.42). These results were robust to several sensitivity analyses. DISCUSSION: We find an association in men who are taking Tz/Dz/Az and a lower hazard of DLB compared with similar men taking other medications. When combined with the literature of Tz/Dz/Az on Parkinson disease, our findings suggest that glycolysis-enhancing drugs may be broadly protective in neurodegenerative synucleinopathies. A future randomized trial is required to assess these associations for causality. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that Tz/Dz/Az use reduces the rate of developing DLB in adult men.


Subject(s)
Adrenergic alpha-1 Receptor Antagonists , Doxazosin , Lewy Body Disease , Prazosin , Quinazolines , Humans , Male , Doxazosin/therapeutic use , Aged , Prazosin/analogs & derivatives , Prazosin/therapeutic use , Lewy Body Disease/drug therapy , Adrenergic alpha-1 Receptor Antagonists/therapeutic use , Quinazolines/therapeutic use , Quinazolines/adverse effects , Aged, 80 and over , Tamsulosin/therapeutic use , Prostatic Hyperplasia/drug therapy , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacology , Middle Aged , Cohort Studies
16.
Pharmacol Rep ; 76(4): 807-822, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38858312

ABSTRACT

BACKGROUND: Apart from antagonizing ß-adrenoceptors, carvedilol antagonizes vascular α1-adrenoceptors and activates G protein-independent signaling. Even though it is a commonly used antihypertensive and α1-adrenoceptors are essential for the treatment of voiding symptoms in benign prostatic hyperplasia, its actions in the human prostate are still unknown. Here, we examined carvedilol effects on contractions of human prostate tissues, and on stromal cell growth. METHODS: Contractions of prostate tissues from radical prostatectomy were induced by electric field stimulation (EFS) or α1-agonists. Growth-related functions were examined in cultured stromal cells. RESULTS: Concentration-response curves for phenylephrine, methoxamine and noradrenaline were right shifted by carvedilol (0.1-10 µM), around half a magnitude with 100 nM, half to one magnitude with 1 µM, and two magnitudes with 10 µM. Right shifts were reflected by increased EC50 values for agonists, with unchanged Emax values. EFS-induced contractions were reduced by 21-54% with 0.01-1 µM carvedilol, and by 94% by 10 µM. Colony numbers of stromal cells were increased by 500 nM, but reduced by 1-10 µM carvedilol, while all concentrations reduced colony size. Decreases in viability were time-dependent with 0.1-0.3 µM, but complete with 10 µM. Proliferation was slightly increased by 0.1-0.5 µM, but reduced with 1-10 µM. CONCLUSIONS: Carvedilol antagonizes α1-adrenoceptors in the human prostate, starting with concentrations in ranges of known plasma levels. In vitro, effect sizes resemble those of α1-blockers used for the treatment of voiding symptoms, which requires concentrations beyond plasma levels. Bidirectional and dynamic effects on the growth of stromal cells may be attributed to "biased agonism".


Subject(s)
Carvedilol , Cell Proliferation , Dose-Response Relationship, Drug , Prostate , Stromal Cells , Carvedilol/pharmacology , Humans , Male , Stromal Cells/drug effects , Stromal Cells/metabolism , Prostate/drug effects , Cell Proliferation/drug effects , Muscle Contraction/drug effects , Adrenergic alpha-1 Receptor Antagonists/pharmacology , Cells, Cultured , Electric Stimulation , Norepinephrine/pharmacology , Propanolamines/pharmacology , Middle Aged , Aged , Methoxamine/pharmacology , Phenylephrine/pharmacology , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/pathology , Adrenergic alpha-1 Receptor Agonists/pharmacology , Receptors, Adrenergic, alpha-1/drug effects , Receptors, Adrenergic, alpha-1/metabolism
18.
J Ethnopharmacol ; 331: 118301, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38735419

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Many ethnopharmacological properties (anti-tumor, etc.) have been credited to Plectranthus esculentus tuber but the scientific basis has not been established. AIM OF THE STUDY: To evaluate the effect of methanol extract of P. esculentus tuber (MEPET) (phase 1) and its fractions (phase 2) on benign prostatic hyperplasia (BPH) in rats. MATERIALS AND METHODS: The study was conducted in two phases. Phase 1, thirty-five male albino rats (6 weeks old) were divided into seven groups of five rats each: normal control (NC) received olive oil (subcutaneously) and water (orally); disease control (DC) received testosterone propionate (TP) (3 mg/kg) and water; test groups (1,2,3 and 4) received TP + MEPET at 100, 200, 400, 600 mg/kg respectively; positive control, received TP + finasteride (5 mg/70 kg). After 28 days, their relative prostate weights (RPW) and prostate specific antigen (PSA) were determined. Phase 2, thirty rats were divided into 6 groups of 5 rats each: NC received olive oil (subcutaneously daily) and dimethyl sulfoxide (DMSO) (orally); DC received TP (3 mg/kg), and DMSO; test group 1 received TP and aqueous fraction of MEPET (400 mg/kg); test group 2 received TP and methanol fraction of MEPET (400 mg/kg); test group 3 received TP, and ethyl acetate fraction of MEPET (400 mg/kg); positive control received TP and finasteride (5 mg/70 kg). After 28 days, their erythrocyte sedimentation rates, RPW, prostate levels of PSA, DHT, inflammatory, apoptotic markers and prostate histology were determined. RESULTS: Ethyl acetate fraction of MEPET modulated most of the parameters of BPH in the rats in a manner akin to finasteride as corroborated by prostate histology. CONCLUSIONS: EFPET could be useful in the treatment of BPH.


Subject(s)
Methanol , Plant Extracts , Plectranthus , Prostatic Hyperplasia , Rats, Wistar , Animals , Male , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/pathology , Prostatic Hyperplasia/chemically induced , Plant Extracts/pharmacology , Methanol/chemistry , Plectranthus/chemistry , Rats , Prostate/drug effects , Prostate/pathology , Prostate-Specific Antigen/blood , Plant Tubers , Organ Size/drug effects , Solvents/chemistry , Testosterone Propionate
19.
Sci Rep ; 14(1): 11116, 2024 05 15.
Article in English | MEDLINE | ID: mdl-38750153

ABSTRACT

Despite the availability of various drugs for benign prostatic hyperplasia (BPH), alpha(α)-blockers are the preferred first-line treatment. However, there remains a scarcity of direct comparisons among various α-blockers. Therefore, this network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of α-blockers in the management of BPH. A comprehensive electronic search covered PubMed, Embase, Ovid MEDLINE, and Cochrane Library until August 2023. The primary endpoints comprised international prostate symptom score (IPSS), maximum flow rate (Qmax), quality of life (QoL), and post-void residual volume (PVR), while treatment-emergent adverse events (TEAEs) were considered as secondary endpoints. This NMA synthesized evidence from 22 studies covering 3371 patients with six kinds of α-blockers with 12 dose categories. IPSS has been considerably improved by tamsulosin 0.4 mg, naftopidil 50 mg and silodosin 8 mg as compared to the placebo. Based on the p-score, tamsulosin 0.4 mg had the highest probability of ranking for IPSS, PVR, and Qmax, whereas doxazosin 8 mg had the highest probability of improving QoL. A total of 297 adverse events were reported among all the α-blockers, silodosin has reported a notable number of TEAEs. Current evidence supports α-blockers are effective in IPSS reduction and are considered safer. Larger sample size with long-term studies are needed to refine estimates of IPSS, QoL, PVR, and Qmax outcomes in α-blocker users.


Subject(s)
Adrenergic alpha-Antagonists , Network Meta-Analysis , Prostatic Hyperplasia , Quality of Life , Humans , Prostatic Hyperplasia/drug therapy , Male , Adrenergic alpha-Antagonists/therapeutic use , Adrenergic alpha-Antagonists/adverse effects , Treatment Outcome , Randomized Controlled Trials as Topic , Tamsulosin/therapeutic use
20.
Urologie ; 63(7): 653-657, 2024 Jul.
Article in German | MEDLINE | ID: mdl-38698262

ABSTRACT

During the last two decades botulinum toxin has also conquered urology. Botulinum toxin reduces the contractility and sensitivity of the detrusor muscle and relieves pain. It is therefore a promising drug whose use in men also appears promising. The following article highlights the practical relevance of botulinum toxin for male lower urinary tract symptoms (LUTS). But first of all, a distinction must be made between use in male LUTS due to benign prostate syndrome (BPS) and use in cases of overactive bladder (OAB) alone. A differentiated diagnosis and treatment of male LUTS is therefore essential.


Subject(s)
Lower Urinary Tract Symptoms , Urinary Bladder, Overactive , Humans , Male , Lower Urinary Tract Symptoms/drug therapy , Urinary Bladder, Overactive/drug therapy , Botulinum Toxins/therapeutic use , Botulinum Toxins, Type A/therapeutic use , Botulinum Toxins, Type A/administration & dosage , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/complications , Neuromuscular Agents/therapeutic use , Neuromuscular Agents/pharmacology
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