RESUMEN
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.
Asunto(s)
Factor 9 de Crecimiento de Fibroblastos , Fibrosis , MicroARNs , Inhibidores de Fosfodiesterasa 5 , Hiperplasia Prostática , Tadalafilo , Masculino , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/genética , MicroARNs/genética , MicroARNs/metabolismo , Tadalafilo/farmacología , Inhibidores de Fosfodiesterasa 5/farmacología , Humanos , Factor 9 de Crecimiento de Fibroblastos/metabolismo , Factor 9 de Crecimiento de Fibroblastos/genética , Próstata/efectos de los fármacos , Próstata/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Proliferación Celular/efectos de los fármacosRESUMEN
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.
Asunto(s)
Apoptosis , Proliferación Celular , Dinaminas , Dinámicas Mitocondriales , Panax , Hiperplasia Prostática , Receptores Androgénicos , Transducción de Señal , Animales , Humanos , Masculino , Ratas , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dinaminas/metabolismo , Dinámicas Mitocondriales/efectos de los fármacos , Panax/química , Extractos Vegetales/farmacología , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/metabolismo , Ratas Sprague-Dawley , Receptores Androgénicos/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
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.
Asunto(s)
Ageratum , Apoptosis , Proliferación Celular , Extractos Vegetales , Próstata , Hiperplasia Prostática , Ratas Sprague-Dawley , Masculino , Animales , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/patología , Extractos Vegetales/farmacología , Apoptosis/efectos de los fármacos , Próstata/efectos de los fármacos , Próstata/patología , Ratas , Ageratum/química , Proliferación Celular/efectos de los fármacos , Testosterona/sangre , Propionato de Testosterona , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , FitoterapiaRESUMEN
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.
Asunto(s)
Medicamentos Herbarios Chinos , Hiperplasia Prostática , Ratas Sprague-Dawley , Testosterona , Animales , Masculino , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/inducido químicamente , Medicamentos Herbarios Chinos/administración & dosificación , Ratas , Testosterona/sangre , Humanos , Estrés Oxidativo/efectos de los fármacos , Próstata/efectos de los fármacos , Próstata/metabolismo , Próstata/patologíaAsunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1 , Hiperplasia Prostática , Tamsulosina , Humanos , Tamsulosina/uso terapéutico , Tamsulosina/administración & dosificación , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/complicaciones , Masculino , Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Insuficiencia del TratamientoAsunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1 , Hiperplasia Prostática , Tamsulosina , Humanos , Tamsulosina/uso terapéutico , Tamsulosina/administración & dosificación , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/cirugía , Masculino , Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Insuficiencia del TratamientoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Anemarrhena asphodeloides Bunge (Ane) and Phellodendron chinense C. K. Schneid (Phe) is classical herb pair in traditional Chinese medicine, commonly used to ameliorate the symptoms of Benign Prostatic Hyperplasia (BPH). However, the mechanisms underlying this effect are remained indistinct. AIM OF THE STUDY: This study aimed to clarify potential therapeutic mechanisms of herb pair on BPH from a metabolic perspective. MATERIALS AND METHODS: Testosterone propionate-induced BPH rat model was established, prostatic parameters, histopathology and the levels of serum dihydrotestosterone (DHT) and testosterone (T) were used to evaluate the pharmacological effect of the herb pair on BPH. Subsequently, untargeted metabolomics of prostate tissues samples was performed by UHPLC-Q-Exactive-Orbitrap-MS, followed by multivariate statistical analysis. Targeted metabolomics by UHPLC-QQQ-MS was further utilized to verify and supplement the results of lipids and amino acids found by untargeted metabolomics, clarifying the relationship between disease, herbal pair and metabolism pathway. RESULTS: The study found that Ane-Phe could relieve the progression of BPH and regulate metabolic imbalances. The levels of 13 metabolites decreased and 11 increased in prostatic tissues including glycerolphospholipid, arachidonic acid, citric acid and so on, these altered metabolites were primarily associated with TCA cycle, arachidonic acid metabolism, lipid metabolism and amino acid metabolism. Furthermore, targeted metabolomics was fulfilled to further analyze the lipid metabolism disorders, the levels of 5 lipids in serum and 21 in prostatic tissues were changed in the herb pair group compared to the model group, which closely related to glycerophospholipid, sphingolipid and glycerolipid metabolism. Besides, amino acid metabolism may be regulated by activating arginine metabolism pathway. CONCLUSIONS: In this study, the combination of untargeted metabolomics and targeted metabolomics was applied to explore therapeutic mechanisms of Ane-Phe on BPH. In summary, Ane-Phe could improve the levels of endogenous metabolites by regulating multiple metabolic pathways and plays a role in energy supply, anti-inflammation and oxidative stress in BPH treatment.
Asunto(s)
Anemarrhena , Metabolómica , Phellodendron , Hiperplasia Prostática , Ratas Sprague-Dawley , Masculino , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Animales , Phellodendron/química , Anemarrhena/química , Ratas , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Próstata/efectos de los fármacos , Próstata/metabolismo , Próstata/patología , Modelos Animales de Enfermedad , Cromatografía Líquida de Alta PresiónRESUMEN
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.
Asunto(s)
Hiperplasia Prostática , Tamsulosina , Humanos , Hiperplasia Prostática/tratamiento farmacológico , Masculino , Tamsulosina/farmacocinética , Tamsulosina/uso terapéutico , Anciano , Persona de Mediana Edad , Antagonistas de Receptores Adrenérgicos alfa 1/farmacocinética , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Anciano de 80 o más Años , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Síntomas del Sistema Urinario Inferior/etiologíaRESUMEN
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.
Asunto(s)
Inhibidores de 5-alfa-Reductasa , Dutasterida , Finasterida , Degeneración Macular , Hiperplasia Prostática , Tamsulosina , Humanos , Inhibidores de 5-alfa-Reductasa/efectos adversos , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Masculino , Anciano , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/epidemiología , Estudios Retrospectivos , Taiwán/epidemiología , Incidencia , Degeneración Macular/epidemiología , Degeneración Macular/diagnóstico , Degeneración Macular/inducido químicamente , Dutasterida/uso terapéutico , Dutasterida/efectos adversos , Tamsulosina/uso terapéutico , Tamsulosina/efectos adversos , Finasterida/efectos adversos , Finasterida/uso terapéutico , Factores de Riesgo , Persona de Mediana Edad , Medición de Riesgo , Bases de Datos FactualesAsunto(s)
Inhibidores de 5-alfa-Reductasa , Finasterida , Humanos , Finasterida/efectos adversos , Finasterida/uso terapéutico , Inhibidores de 5-alfa-Reductasa/efectos adversos , Masculino , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/inducido químicamente , Hiperplasia Prostática/tratamiento farmacológicoRESUMEN
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 â4)-α-D-Glcp-(1â, branched units comprised α-D-Glcp-(1â6)-α-D-Glcp-(1â, ß-D-Glcp-(1â6)-ß-D-Glcp-(1â and α-D-Glcp-(1â 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.
Asunto(s)
Epimedium , Flavonoides , Glucanos , Hiperplasia Prostática , Epimedium/química , Masculino , Glucanos/química , Glucanos/farmacología , Glucanos/aislamiento & purificación , Hiperplasia Prostática/tratamiento farmacológico , Flavonoides/química , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Animales , Portadores de Fármacos/química , Humanos , Microbioma Gastrointestinal/efectos de los fármacosRESUMEN
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.
Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1 , Presión Sanguínea , Fuerza de la Mano , Hipertensión , Prazosina , Hiperplasia Prostática , Tamsulosina , Humanos , Masculino , Estudios Transversales , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/fisiopatología , Prazosina/farmacología , Prazosina/uso terapéutico , Prazosina/administración & dosificación , Tamsulosina/uso terapéutico , Persona de Mediana Edad , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Fuerza de la Mano/fisiología , Anciano , Antihipertensivos/uso terapéutico , IndiaRESUMEN
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.
Asunto(s)
Inhibidores de 5-alfa-Reductasa , Antagonistas Adrenérgicos alfa , Análisis Costo-Beneficio , Hiperplasia Prostática , Calidad de Vida , Humanos , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/economía , Masculino , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Inhibidores de 5-alfa-Reductasa/economía , Antagonistas Adrenérgicos alfa/uso terapéutico , Antagonistas Adrenérgicos alfa/economía , Prioridad del Paciente , Análisis de Costo-EfectividadRESUMEN
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.
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Antagonistas de Receptores Adrenérgicos alfa 1 , Doxazosina , Enfermedad por Cuerpos de Lewy , Prazosina , Quinazolinas , Humanos , Masculino , Doxazosina/uso terapéutico , Anciano , Prazosina/análogos & derivados , Prazosina/uso terapéutico , Enfermedad por Cuerpos de Lewy/tratamiento farmacológico , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Quinazolinas/uso terapéutico , Quinazolinas/efectos adversos , Anciano de 80 o más Años , Tamsulosina/uso terapéutico , Hiperplasia Prostática/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología , Persona de Mediana Edad , Estudios de CohortesRESUMEN
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".
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Carvedilol , Proliferación Celular , Relación Dosis-Respuesta a Droga , Próstata , Células del Estroma , Carvedilol/farmacología , Humanos , Masculino , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Próstata/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Células Cultivadas , Estimulación Eléctrica , Norepinefrina/farmacología , Propanolaminas/farmacología , Persona de Mediana Edad , Anciano , Metoxamina/farmacología , Fenilefrina/farmacología , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/patología , Agonistas de Receptores Adrenérgicos alfa 1/farmacología , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Receptores Adrenérgicos alfa 1/metabolismoRESUMEN
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.
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Anemarrhena , Medicamentos Herbarios Chinos , Metabolómica , Farmacología en Red , Phellodendron , Hiperplasia Prostática , Transducción de Señal , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/sangre , Masculino , Anemarrhena/química , Metabolómica/métodos , Farmacología en Red/métodos , Phellodendron/química , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Transducción de Señal/efectos de los fármacos , Cromatografía Líquida de Alta Presión/métodos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Extractos Vegetales/farmacologíaRESUMEN
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.
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Antagonistas de Receptores Adrenérgicos alfa 1 , Hiperplasia Prostática , Tamsulosina , Humanos , Tamsulosina/administración & dosificación , Tamsulosina/uso terapéutico , Masculino , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Insuficiencia del Tratamiento , Resultado del Tratamiento , Esquema de MedicaciónRESUMEN
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.
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Antagonistas Adrenérgicos alfa , Metaanálisis en Red , Hiperplasia Prostática , Calidad de Vida , Humanos , Hiperplasia Prostática/tratamiento farmacológico , Masculino , Antagonistas Adrenérgicos alfa/uso terapéutico , Antagonistas Adrenérgicos alfa/efectos adversos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Tamsulosina/uso terapéuticoRESUMEN
PURPOSE: The efficacy and safety of vibegron, a ß3-adrenergic receptor agonist, was assessed among men with symptoms of overactive bladder (OAB) receiving pharmacologic treatment for benign prostatic hyperplasia (BPH) in a phase 3 randomized controlled trial. MATERIALS AND METHODS: Men ≥ 45 years with OAB symptoms and BPH, treated with α-blocker with/without 5α-reductase inhibitors, were randomized 1:1 to vibegron or placebo for 24 weeks. Coprimary end points were change from baseline at week 12 in mean daily micturitions and urgency episodes. Secondary end points were change from baseline at week 12 in mean nightly nocturia and daily urge urinary incontinence episodes, International Prostate Symptom Scoreâstorage score, and volume voided per micturition. Safety was evaluated via adverse events (AEs). RESULTS: Of 1105 participants randomized, 965 (87.3%) completed the trial. At week 12, vibegron was associated with significant reductions vs placebo in daily micturitions (least squares mean difference [95% CI], -0.74 [-1.02, -0.46]; P < .0001) and urgency episodes (-0.95 [-1.37, -0.54]; P < .0001). Vibegron was also associated with significant improvements vs placebo at week 12 in nocturia episodes (least squares mean difference, -0.22 [-0.36, -0.09]; P = .002), urge urinary incontinence episodes (-0.80 [-1.33, -0.27]; P = .003), International Prostate Symptom Scoreâstorage scores (-0.9 [-1.2, -0.6]; P < .0001), and volume voided (15.07 mL [9.13-21.02]; P < .0001). AE rates were similar in vibegron (45.0%) and placebo (39.0%) arms; AEs occurring in ≥ 2% of participants were hypertension (9.0% vs 8.3%), COVID-19 (4.0% vs 3.1%), UTI (2.5% vs 2.2%), and hematuria (2.0% vs 2.5%). CONCLUSIONS: In this trial, vibegron met all primary and secondary end points and was safe and well tolerated in men with OAB symptoms and pharmacologically treated BPH.