Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 561
Filtrar
1.
Medicine (Baltimore) ; 99(12): e19540, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195959

RESUMO

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease in men. As part of traditional Traditional Chinese medicine, acupuncture has been widely used in clinical practice. In order to evaluate the exact effect of acupuncture on the clinical efficacy of CP/CPPS, this experiment uses randomized controlled experiments. METHODS/DESIGN: This pragmatic randomized controlled trial will recruit 166 patients who are diagnosed with CP/CPPS. Simple randomization to conventional drug treatment with a 1:1 allocation ratio will be used. Ten 30-minute acupuncture sessions will be provided to patients assigned to the Intervention group. All participants will continue to receive conventional drug treatment. The selection of outcomes will be evaluated by Health's Symptom Score Index (NIH-CPSI) score at week 4. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of acupuncture for patients with CP/CPPS. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR1900021132, Registered on 29 January 2019.


Assuntos
Terapia por Acupuntura/métodos , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Dor Pélvica/terapia , Prostatite/terapia , Tansulosina/uso terapêutico , Terapia por Acupuntura/economia , Administração Oral , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , China/epidemiologia , Doença Crônica , Terapia Combinada , Análise Custo-Benefício , Preparações de Ação Retardada , Estudos de Viabilidade , Humanos , Masculino , Dor Pélvica/diagnóstico , Prostatite/diagnóstico , Síndrome , Tansulosina/administração & dosagem , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(3): e18712, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011446

RESUMO

BACKGROUND: Drug therapy for lower urinary tract symptoms (LUTS) secondary to benign prostate hyperplasia (BPH) is a major and popular method. However, the therapeutic strategy is still not clear enough up to now. The purpose of this study was to compare the relative safety and efficacy of different types of phosphodiesterase type 5 inhibitors (PDE5-Is) with tamsulosin for the treatment of LUTS secondary to BPH. METHODS: Databases including PubMed, OpenGrey, Embase, Cochrane Library, and Web of Science will be searched to identify qualified studies. We will use the Stata version 13.0 to conduct the network meta-analysis (NMA) with a random or fixed effects model of Bayesian framework. International prostate symptom score (IPSS), maximum urinary flow fate (Qmax) and their credible intervals (CI) will be used to compare every medical intervention with the efficacy and safety, including sildenafil plus tamsulosin, tadalafil plus tamsulosin, vardenafil plus tamsulosin. And the ranking of probability of different interventions will be estimated by comparing the surface under the cumulative ranking curve (SUCRA). RESULTS: A high quality-synthesis of the current evidence for comparing with different doses or types of PDE5-Is combined with tamsulosin to the treatment of LUTS secondary to BPH will be provided. CONCLUSIONS: This NMA and systematic review will generate evidence to help choose the best combination for treatment of LUTS secondary to BPH.PROSPERO registration number: PROSPERO CRD 42019139062.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Tansulosina/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Teorema de Bayes , Quimioterapia Combinada , Humanos , Masculino , Meta-Análise em Rede , Inibidores da Fosfodiesterase 5/administração & dosagem , Inibidores da Fosfodiesterase 5/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Citrato de Sildenafila/uso terapêutico , Tadalafila/uso terapêutico , Tansulosina/administração & dosagem , Tansulosina/efeitos adversos , Dicloridrato de Vardenafila/uso terapêutico
3.
Medicine (Baltimore) ; 99(4): e18802, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977871

RESUMO

BACKGROUND: We conducted a meta-analysis to assess the efficacy and safety of mirabegron on overactive bladder (OAB) induced by benign prostatic hyperplasia (BPH) in men receiving tamsulosin therapy. METHODS: We performed the analysis by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The databases including MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were retrieved to get information regarding randomized controlled trials of mirabegron on OAB induced by BPH in men receiving tamsulosin therapy. We also searched the references of included literatures. RESULTS: Three randomized controlled trials containing a total of 1317 BPH patients were included in the analysis. Co-primary efficacy end points: the mean number of micturitions per day [the mean difference (MD) = -0.27, 95% confidence interval (CI): -0.46 to -0.09, P = .004], the urgency episodes per day (the MD = -0.50, 95% CI: -0.77 to -0.22, P = .0004), the total OAB symptom score (the MD = -0.69, 95% CI: -1.00 to -0.38, P < .0001), and mean volume voided (the MD = 10.76, 95% CI: 4.87-16.64, P = .0003) indicated that mirabegron was effective in treating OAB induced by BPH in men receiving tamsulosin therapy. Safety assessments that included treatment-emergent adverse events (odds ratio = 0.88, 95% CI: 0.68-1.13, P = .31) indicated that mirabegron was well tolerated with the exception of post-void residual urine volume (MD = 12.02, 95% CI: 6.01-18.04, P < .0001). CONCLUSIONS: This analysis demonstrates that mirabegron is an effective and safe treatment for OAB symptoms induced by BPH in men receiving tamsulosin therapy with a low occurrence of side effects. Besides, we should be aware that the administration of mirabegron might have the risk of increasing post-void residual urine volume.


Assuntos
Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Acetanilidas , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Humanos , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tansulosina/uso terapêutico , Tiazóis , Resultado do Tratamento , Bexiga Urinária Hiperativa/etiologia
4.
Curr Med Sci ; 39(5): 707-718, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612387

RESUMO

This study aimed to evaluate the effectiveness of tamsulosin monotherapy for the treatment of ureteral stent-related symptoms (SRSs) and compare it with that of solifenacin monotherapy and combined therapy of tamsulosin and silifenacin. Randomized controlled trials (RCTs), which evaluated the effectiveness of tamsulosin for the treatment of SRSs, were searched from the databases PubMed, EMBASE and the Cochrane Library published up to November 2018. Eight RCTs involving 1087 participants were finally included in this meta-analysis. The results showed that tamsulosin monotherapy could significantly decrease the urinary symptoms [mean difference (MD) -7.56, 95% confidence interval (CI) (-11.47, -3.65), P=0.0001] and body pain [MD -5.25, 95% CI (-8.03, -2.46), P=0.0002], and improve the sexual performance [MD -1.06, 95% CI (-1.89, -0.24), P=0.01] compared with the control group. Moreover, there was no significant difference between tamsulosin monotherapy and solifenacin monotherapy in all outcomes except for significantly better sexual performance in solifenacin group [MD 0.29, 95% CI (0.06, 0.51), P=0.01]. In addition, the effectiveness of combined therapy of tamsulosin and solifenacin was not superior to that of tamsulosin monotherapy. Our study demonstrated that tamsulosin monotherapy was effective for the treatment of patients with SRSs; evident superiority could not be found for therapy of tamsulosin and solifenacin combined.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Succinato de Solifenacina/uso terapêutico , Stents/efeitos adversos , Tansulosina/uso terapêutico , Agentes Urológicos/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Doenças Ureterais/cirurgia
5.
Presse Med ; 48(11 Pt 1): 1222-1228, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31303372

RESUMO

Erectile dysfunction (ED) is not routinely discussed with patients in cardiology practices whereas it may impact the ability of patients to stay on therapy. Most of the studies about ED and antihypertensive therapies have several methodological limitations. Diuretics and beta-blockers have been shown to have a deleterious effect on ED. ISRA inhibitors, calcium antagonists, vasodilator beta-blockers and alpha-blockers have been shown to have a neutral impact on ED. Angiotensin 2 inhibitors, nebivolol and alpha-blockers use has sometimes beneficial effect on ED. In case of ED due to antihypertensive treatment, drugs can be switched each other but careful attention in patients with a high cardiovascular risk is required.


Assuntos
Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológico , Disfunções Sexuais Fisiológicas/induzido quimicamente , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Bloqueadores do Receptor Tipo 2 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Diuréticos/efeitos adversos , Diuréticos/uso terapêutico , Substituição de Medicamentos , Humanos , Masculino , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Fatores de Risco , Disfunções Sexuais Fisiológicas/prevenção & controle
6.
J Urol ; 202(6): 1240-1247, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31188728

RESUMO

PURPOSE: Medications targeting androgen receptor activity (eg finasteride) or smooth muscle contractility (eg doxazosin) do not resolve lower urinary tract symptoms indicative of lower urinary tract dysfunction in an important subgroup of men. Recently fibrosis has been implicated as another pathobiology contributing to male lower urinary tract symptoms but to our knowledge no systematic studies have been done to assess fibrosis in the context of medical treatment. We determine whether fibrotic changes in the prostate transition zone are associated with an increased risk of clinical progression in participants treated with doxazosin, finasteride or finasteride plus doxazosin in the MTOPS (Medical Therapy of Prostatic Symptoms) study. MATERIALS AND METHODS: Transition zone biopsy tissues from men who did or did not experience clinical progression on placebo, doxazosin, finasteride or combination therapy were assessed for collagen content and architectural changes using picrosirius red birefringence and CT-FIRE (Curvelet Transform-Fiber Extraction) analysis. Correlations were made with annotated demographic and clinical data. Statistical analyses were done with the Pearson correlation coefficient, ANOVA and the t-test. RESULTS: High levels of wavy, aligned prostate transition zone collagen significantly correlated with an increased risk of clinical progression among MTOPS trial participants treated with doxazosin plus finasteride, particularly those with a high body mass index. CONCLUSIONS: Fibrotic changes in the prostate transition zone are associated with an increased risk of clinical progression in men treated with doxazosin plus finasteride. Antifibrotic therapeutics might provide a new treatment approach in men with lower urinary tract dysfunction who do not respond to current medical treatment approaches.


Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Próstata/patologia , Hiperplasia Prostática/tratamento farmacológico , Biópsia , Estudos de Coortes , Progressão da Doença , Doxazossina/uso terapêutico , Quimioterapia Combinada/métodos , Fibrose , Finasterida/uso terapêutico , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/complicações , Hiperplasia Prostática/patologia , Fatores de Tempo , Resultado do Tratamento
7.
Tokai J Exp Clin Med ; 44(2): 29-30, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31250422

RESUMO

The newer generation non selective vasodilating beta adrenergic blocking agent Carvedilol, also has an alpha 1 adrenoceptor antagonistic effect and is widely used in treating various cardiovascular diseases. It is a selective alpha and non-selective beta blocker. It's side effects are vast and not limited to any particular organ system, the neuropsychiatric adverse effects include; somnolence, nervousness, sleep disorder, aggravated depression, vivid dreams, delirium, psychosis, impaired concentration, abnormal thinking, paroniria, and emotional lability. Hallucinations are rarely reported and as far as we know the only reported couple of cases were on metoprolol and propranolol, none has been reported with Carvedilol.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Antagonistas Adrenérgicos beta/efeitos adversos , Carvedilol/efeitos adversos , Alucinações/induzido quimicamente , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Carvedilol/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico
8.
Urologiia ; (2): 67-72, 2019 Jun.
Artigo em Russo | MEDLINE | ID: mdl-31162905

RESUMO

Benign prostatic hyperplasia commonly is the most common cause of bladder outlet obstruction and can result in storage and micturition symptoms in men older than 40 years. Nowadays the 1-adrenoreceptor antagonists are the first-line drug for treatment of the lower urinary tract symptoms (LUTS). However, 1-adrenoreceptors are known to be present in other tissues and this fact could be a reason of potential risk of adverse events, associated with changes in peripheral vascular tone, such as orthostatic hypotension, syncopal states, dizziness, etc., especially in patients of advanced age, and those affected by cardiovascular diseases and taking essential drugs. A highly selective -adrenergic blocker silodosin is characterized by a lower rate of mentioned adverse events, comparable with placebo. Silodosin is also highly effective in treating of both types of LUTS in these patients, both as monotherapy and in combination with other drugs. A detailed analysis of clinical data confirming the high efficacy and safety of silodosin is presented in this review of the literature.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Indóis/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Hiperplasia Prostática/complicações
10.
Invest Ophthalmol Vis Sci ; 60(5): 1442-1453, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30947334

RESUMO

Purpose: The purpose of this study was to test the extent of light damage in different models of night blindness and apply these paradigms in testing the therapeutic efficacy of combination therapy by drugs acting on the Gi, Gs, and Gq protein-coupled receptors. Methods: Acute bright light exposure was used to test susceptibility to light damage in mice lacking the following crucial phototransduction proteins: rod transducin (GNAT1), cone transducin (GNAT2), visual arrestin 1 (ARR1), and rhodopsin kinase 1 (GRK1). Mice were intraperitoneally injected with either vehicle or drug combination consisting of metoprolol (ß1-receptor antagonist), bromocriptine (dopamine family-2 receptor agonist) and tamsulosin (α1-receptor antagonist) before bright light exposure. Light damage was primarily assessed with optical coherence tomography and inspection of cone population in retinal whole mounts. Retinal inflammation was assessed in a subset of experiments using autofluorescence imaging by scanning laser ophthalmoscopy and by postmortem inspection of microglia and astrocyte activity. Results: The Gnat1-/- mice showed slightly increased susceptibility to rod light damage, whereas the Gnat2-/- mice were very resistant. The Arr1-/- and Grk1-/- mice were sensitive for both rod and cone light damage and showed robust retinal inflammation 7 days after bright light exposure. Pretreatment with metoprolol + bromocriptine + tamsulosin rescued the retina in all genetic backgrounds, starting at doses of 0.2 mg/kg metoprolol, 0.02 mg/kg bromocriptine, and 0.01 mg/kg tamsulosin in the Gnat1-/- mice. The therapeutic drug doses increased in parallel with light-damage severity. Conclusions: Our results suggest that congenital stationary night blindness and Oguchi disease patients can be at an elevated risk of the toxic effects of bright light. Furthermore, systems pharmacology drug regimens that stimulate Gi signaling and attenuate Gs and Gq signaling present a promising disease-modifying therapy for photoreceptor degenerative diseases.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Bromocriptina/farmacologia , Luz/efeitos adversos , Metoprolol/farmacologia , Cegueira Noturna/tratamento farmacológico , Tansulosina/farmacologia , Animais , Arrestinas/deficiência , Modelos Animais de Doenças , Receptor Quinase 1 Acoplada a Proteína G/deficiência , Camundongos , Transducina/deficiência , Estados Unidos , United States Food and Drug Administration
11.
Urol Int ; 102(4): 482-486, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30840961

RESUMO

INTRODUCTION: Alpha-adrenergic blockers are now the cornerstone medication in management of lower urinary tract symptom (LUTS); however, the associated treatment-related abnormal ejaculation could be a bothersome event. This is a comparative study among different methods of tamsulosin administration in terms of efficacy, recoverability of ejaculatory function, and quality of life (QoL) in men with tamsulosin-related abnormal ejaculation. PATIENTS AND METHODS: Sexually active men receiving tamsulosin for LUTS who were bothered by treatment-related abnormal ejaculation following initiation of tamsulosin were randomized into 3 groups; group A received intermittent-full-standard-dose, group B received low-dose-tamsulosin, and group C received full-standard-dose tamsulosin The status of ejaculatory function, IPSS, QoL score, and Q-Max were measured at baseline and 3 months later. RESULTS: A total of 93 men with mean age of 53.1 years were included in the study, 3-months after randomization, statistically significant improvements in IPSS, QoL index, and Q-Max in comparison to pre-treatment levels were noted. Restoration of normal ejaculation was reported by 74.1 and 90.3% of patients in group A and B, respectively, versus none in group C. The QoL score was significant when comparing group A to the other groups; finally, the Q-Max was significant when comparing group C to the other groups. CONCLUSION: For patients bothered by tamsulosin-related abnormal ejaculation, a significant improvement in the QoL, without deviation from the therapeutic purpose of treatment, can be achieved by administration of 0.4 mg tamsulosin every other day.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Ejaculação/efeitos dos fármacos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Qualidade de Vida , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Tansulosina/administração & dosagem , Tansulosina/efeitos adversos , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Idoso , Esquema de Medicação , Humanos , Sintomas do Trato Urinário Inferior/complicações , Masculino , Pessoa de Meia-Idade , Dor Pélvica/tratamento farmacológico , Estudos Prospectivos , Prostatite/tratamento farmacológico , Disfunções Sexuais Fisiológicas/psicologia , Resultado do Tratamento
15.
Eur Urol ; 75(5): 788-798, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30773327

RESUMO

CONTEXT: Practice patterns for the management of urinary retention (UR) secondary to benign prostatic obstruction (BPO; UR/BPO) vary widely and remain unstandardized. OBJECTIVE: To review the evidence for managing patients with UR/BPO with pharmacological and nonpharmacological treatments included in the European Association of Urology guidelines on non-neurogenic male lower urinary tract symptoms. EVIDENCE ACQUISITION: Search was conducted up to April 22, 2018, using CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform. This systematic review included randomized controlled trials (RCTs) and prospective comparative studies. Methods as detailed in the Cochrane handbook were followed. Certainty of evidence (CoE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. EVIDENCE SYNTHESIS: Literature search identified 2074 citations. Twenty-one studies were included (qualitative synthesis). The evidence for managing patients with UR/BPO with pharmacological or nonpharmacological treatments is limited. CoE for most outcomes was low/very low. Only α1-blockers (alfuzosin and tamsulosin) have been evaluated in more than one RCT. Pooled results indicated that α1-blockers provided significantly higher rates of successful trial without catheter compared with placebo [alfuzosin: 322/540 (60%) vs 156/400 (39%) (odds ratio {OR} 2.28, 95% confidence interval {CI} 1.55 to 3.36; participants=940; studies=7; I2=41%; low CoE); tamsulosin: 75/158 (47%) vs 40/139 (29%) (OR 2.40, 95% CI 1.29 to 4.45; participants=297; studies=3; I2=30%; low CoE)] with rare adverse events. Similar rates were achieved with tamsulosin or alfuzosin [51/87 (59%) vs 45/84 (54%) (OR 1.28, 95% CI 0.68 to 2.41; participants=171; studies=2; I2=0%; very low CoE)]. Nonpharmacological treatments have been evaluated in RCTs/prospective comparative studies only sporadically. CONCLUSIONS: There is some evidence that usage of α1-blockers (alfuzosin and tamsulosin) may improve resolution of UR/BPO. As most nonpharmacological treatments have not been evaluated in patients with UR/BPO, the evidence is inconclusive about their benefits and harms. PATIENT SUMMARY: There is some evidence that alfuzosin and tamsulosin may increase the rates of successful trial without catheter, but little or no evidence on various nonpharmacological treatment options for managing patients with urinary retention secondary to benign prostatic obstruction.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Hiperplasia Prostática/complicações , Retenção Urinária/etiologia , Retenção Urinária/terapia , Humanos , Masculino , Prostatectomia , Quinazolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tansulosina/uso terapêutico , Cateterismo Urinário
16.
Neuroscience ; 404: 314-325, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30771511

RESUMO

Several studies have demonstrated the antitumor effect of doxazosin, an α1-adrenergic blocker, against glioma and breast, bladder and prostate cancers. Doxazosin is also being evaluated as a treatment for posttraumatic stress disorder (PTSD) and alcoholism, and α1-adrenergic blockers have been linked to neuroprotection in neurodegenerative disorders, such as Alzheimer's Disease (AD). Cancer and AD have an inverse relationship in many aspects, with several factors that contribute to apoptosis inhibition and proliferation being increased in cancers but decreased in AD. Neuroblastoma (NB) is a pediatric tumor derived from embryonic neural-crest cells, with an overall cure rate of 40%, despite aggressive treatment. Thus, due to the need of new therapeutic strategies against NB and neurodegenerative disorders and the inverse relationship between these diseases, we investigated whether doxazosin may serve as an antitumor and neuroprotective agent. We analyzed the drug's effects on undifferentiated and retinoic acid-differentiated SH-SY5Y human NB cells and on an in vitro model of organotypic hippocampal cultures exposed to amyloid-ß. Doxazosin showed antitumor effect on undifferentiated NB cells by induction of apoptosis, necrosis, cell cycle arrest and decrease of p-EGFRTyr1048 levels. On differentiated cells, doxazosin was less cytotoxic and increased p-EGFRTyr1048, p-AktSer473 and p-GSK-3ßSer9 levels. Moreover, the drug was able to protect hippocampal slices from amyloid-ß toxicity through prevention of GSK-3ß activation and of Tau hyperphosphorylation. Therefore, our results show that doxazosin has antitumor activity against undifferentiated NB and is neuroprotective on an in vitro model of Alzheimer's disease.


Assuntos
Doença de Alzheimer/metabolismo , Antineoplásicos/farmacologia , Doxazossina/farmacologia , Neuroblastoma/metabolismo , Fármacos Neuroprotetores/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Doxazossina/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Masculino , Neuroblastoma/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar
17.
Drugs R D ; 19(1): 47-55, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30607819

RESUMO

OBJECTIVES: Our objective was to investigate the effectiveness and safety of silodosin in patients with benign prostatic hyperplasia (BPH) who switched to silodosin from another α1 blocker because of inadequate response. METHODS: This was a prospective observational study conducted at 715 medical facilities in Japan in patients with BPH who received an α1 blocker other than silodosin for at least 3 months but had experienced unsatisfactory treatment outcomes. Patients completed questionnaires, including the International Prostate Symptom Score (IPSS), quality of life (QOL) score and Overactive Bladder Symptom Score (OABSS) at baseline (time of switching) and after 3 months of treatment with silodosin. RESULTS: Overall, 3355 patients were assessed for safety and 3144 patients for effectiveness. Mean ± standard deviation age was 73.1 ± 8.2 years, and most patients had been receiving tamsulosin (53.6%) or naftopidil (45.5%) before silodosin. Silodosin was well tolerated, with an overall incidence of adverse drug reactions of 8.1% and no unexpected safety signals. Significant improvements were observed after switching to silodosin in all effectiveness outcome measures, including total IPSS, all IPSS subscale scores, QOL score, total OABSS, all OABSS subscale scores and residual urine volume. Significant improvements in total IPSS were seen in patients who had been receiving tamsulosin or naftopidil before switching and in almost all other patient subgroups, with the exception of patients with mild symptoms (total IPSS ≤ 7) at baseline. CONCLUSIONS: This post-marketing analysis indicates that switching to silodosin from tamsulosin or naftopidil significantly improved symptoms associated with BPH, and silodosin was well tolerated in Japanese patients.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Indóis/efeitos adversos , Indóis/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Monitoramento Epidemiológico , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Naftalenos/uso terapêutico , Piperazinas/uso terapêutico , Vigilância de Produtos Comercializados , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Tansulosina/uso terapêutico , Resultado do Tratamento
18.
Urol Int ; 102(2): 125-130, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30669141

RESUMO

AIM/OBJECTIVE: To identify trends in the evidence base regarding the effectiveness of using α-blockers in children versus adults and compare outcomes. METHODS: A literature search up using the key words including urolithiasis/renal/ureteric stone in children/paediatric population, medical expulsive treatment (MET), α-blocker/alfuzosin/tamsulosin/doxazosin. Included were randomized or controlled clinical trials in paediatric stone formers (aged ≤18 years). Outcome measures for assessment included the overall stone expulsion rate, expulsion time, the number of pain episodes and adverse drug effects and/or reactions. Further comparison of efficacy levels using respective studies from the adult population was performed in order to identify trends, similarities and differences. RESULTS: A total of 8,259 articles were identified. Full text evaluation was possible for 28 articles. Although the picture is clearer in the paediatric group, the lack of reproducible results in adults certainly poses serious questions about data collection, analysis and interpretation in each individual study. The apparent paradox is due to the methodological differences between studies. CONCLUSION: The effectiveness of α-blockers and other medication as MET needs to be studied in multi-institutional, double-blind, placebo-controlled studies that would aim to prove superiority to placebo in contemporary clinical situations, with realistic end points and standardized outcome measure determination.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Doxazossina/uso terapêutico , Quinazolinas/uso terapêutico , Tansulosina/uso terapêutico , Urolitíase/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Adolescente , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Idade de Início , Criança , Doxazossina/efeitos adversos , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Quinazolinas/efeitos adversos , Indução de Remissão , Tansulosina/efeitos adversos , Resultado do Tratamento , Urolitíase/diagnóstico , Urolitíase/epidemiologia , Agentes Urológicos/efeitos adversos
19.
BJU Int ; 123(1): 124-129, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29917304

RESUMO

OBJECTIVES: To determine whether penile blood pressure (PBP) can be used to identify patients who can benefit from tadalafil treatment, the correlation between PBP at baseline and changes in lower urinary tract symptoms (LUTS) induced by tadalafil treatment was studied prospectively. PATIENTS AND METHODS: Patients with BPH who were poor responders to α1 -blockers and took tadalafil instead of an α1 -blocker were registered between 2014 and 2016. The patients were divided into two groups (low- and high-PBP groups) using the median baseline PBP of 110 mmHg as the threshold. The changes in the International Prostate Symptom Score (IPSS) between before and at 4 and 12 weeks after tadalafil treatment were compared between the low- and high-PBP groups. Multivariate analysis was performed to identify parameters associated with IPSS improvement with tadalafil treatment. RESULTS: In all, 51 patients were investigated. The IPSS in the low-PBP group decreased immediately after the start of treatment, and there was significant improvement in the IPSS from baseline at 4 and 12 weeks after the start of treatment, whilst the IPSS in the high-PBP group did not show significant changes. On multivariate analysis, PBP at baseline, anticholinergic drug use, and IPSS at baseline were significant predictors of a good IPSS response to tadalafil treatment. CONCLUSIONS: This study demonstrated that PBP could reliably identify patients with BPH who could benefit from tadalafil treatment. Patients with low PBP could be better responders to tadalafil.


Assuntos
Pênis/fisiopatologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Prostatismo/tratamento farmacológico , Tadalafila/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/efeitos dos fármacos , Antagonistas Colinérgicos/uso terapêutico , Humanos , Masculino , Seleção de Pacientes , Estudos Prospectivos , Hiperplasia Prostática/complicações , Prostatismo/etiologia , Índice de Gravidade de Doença
20.
Psychopharmacology (Berl) ; 236(1): 273-279, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30112577

RESUMO

RATIONALE: Recovery from a traumatic experience requires extinction of cue-based fear responses, a process that is impaired in post-traumatic stress disorder. While studies suggest a link between fear behavioral flexibility and noradrenaline signaling, the role of specific receptors and brain regions in these effects is unclear. OBJECTIVES: Here, we examine the role of prazosin, an α1-adrenergic receptor (α1-AR) antagonist, in auditory fear conditioning and extinction. METHODS: C57Bl/6N mice were subjected to auditory fear conditioning and extinction in combination with systemic (0.1-2 mg/kg) or local microinjections (3 or 6 mM) of the α1-AR antagonist prazosin into the prelimbic division of medial prefrontal cortex or basolateral amygdala. Conditioned fear and anxiety-like behaviors were compared with vehicle-injected control animals. RESULTS: Mice that received systemic prazosin prior to fear conditioning exhibited similar initial levels of cue-elicited freezing compared to vehicle controls on the following day. However, at all doses tested, fear that was acquired during prazosin treatment was more readily extinguished, whereas anxiety-like behavior on the day of extinction was unaffected. A similar pattern of results was observed when prazosin was microinjected into the basolateral amygdala but not the prelimbic cortex. In contrast to pre-conditioning injections, prazosin administration prior to extinction had no effect on freezing. CONCLUSIONS: Our results indicate that α1-AR activity during aversive conditioning is dispensable for memory acquisition but renders conditioned fear more impervious to extinction. This suggests that behavioral flexibility is constrained by noradrenaline at the time of initial learning via activation of a specific AR isoform.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Prazosina/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Animais , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Extinção Psicológica/fisiologia , Medo/fisiologia , Medo/psicologia , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Prazosina/uso terapêutico , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA