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1.
Medicine (Baltimore) ; 99(23): e20546, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502017

RESUMO

Erectile dysfunction (ED) and depression are closely related. We sought to determine ED and depression were improved by tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, at 5 mg daily, in this case-control study.Participants were men aged 20 to 65 years with ED for >3 months, International Index of Erectile Function-5 (IIEF) score <21 points, and Zung Self-Rating Depression Scale (SDS) survey result >50 points who were willing to participate.On first visit (V1) and after 1 (V2) and 2 months (V3), clinical features were examined using IIEF-5 for diagnosing and evaluating ED, SDS for evaluating depression, and International Prostate Symptom Score and Quality of Life (IPSS/QoL) survey for examining lower urinary tract symptoms (LUTS). Tadalafil 5 mg was administered daily for 2 months.A total of 60 participants were an average age of 58.68 ± 6.71 years. Patient overall average IIEF was 8.76 ±â€Š5.98, showing mild ED symptoms, and total average IPSS 13.74 ±â€Š7.55 showed moderate LUTS. Average overall SDS index was 58.93 ±â€Š9.21, indicating moderate-to-severe findings. Average change in IIEF among all patients revealed significant improvement from V1 to V2 (-2.69 ±â€Š1.22, P = .03) and V1 to V3 (-4.38 ±â€Š1.20, P < 0.01). IPSS also significantly improved from V1 to V3 (3.48 ±â€Š1.37, P = .01), as did SDS index (V1, V2: 4.69 ±â€Š1.89, P = 0.02), (V1, V3: 5.43 ±â€Š1.89, P < .01). Patients with severe IIEF scores (group 1, n = 27) experienced significantly greater improvement in IIEF from V1 to V2 and V1 and V3, compared to those with mild-to-moderate IIEF scores. Both groups improved in SDS index from V1 to V2 and V1 to V3, with the greatest improvement between V1 and V3 for group 1 and V1 and V2 for group 2.Daily tadalafil 5 mg could be helpful for ED patients with depressive symptoms and improved LUTS and quality of life.


Assuntos
Depressão/terapia , Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/administração & dosagem , Tadalafila/administração & dosagem , Adulto , Idoso , Estudos de Casos e Controles , Depressão/complicações , Disfunção Erétil/complicações , Humanos , Sintomas do Trato Urinário Inferior , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto Jovem
2.
Artigo em Inglês | MEDLINE | ID: mdl-32251992

RESUMO

In this paper, an ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF HRMS) method was developed and validated for screening, confirmation and quantitation of 31 anti-impotence compounds potentially illegally added to herbal-based dietary supplements. The analytes were well separated by the mobile phase consisted of 0.1% formic acid solution and acetonitrile with gradient elution at a flow rate of 0.3 mL/min. The MS analysis was operated in positive mode and the mass error of the 31 compounds were below 2.9 ppm. The method validation showed good linearity with coefficients of determination (r2) higher than 0.9973 for all analytes. LODs and LLOQs ranged from 0.005 to 0.50 µg/g or µg /mL and from 0.02 to 1.24 µg /g or µg/mL, respectively. The accuracy was in the range of 86.6% to 113.7%, while the intra-and inter-day precision were in the ranges of 0.9-7.6% and 0.9-11.4%, respectively. The absolute and relative matrix effect were in the range of 65.8-115.6% and 0.6-13.3%. The mean recoveries were in the range of 80.5-116.9%. The stability ranged from 0.4% to 8.5%. Among 200 batches of herbal-based dietary supplements, sildenafil and/or tadalafil were found to be added illegally in two samples, while not very high concentration of icariin was detected in one sample. The Q-TOF mass spectrometry has been proved to be a very powerful and efficient tool for rapid screening of 31 anti-impotence compounds potentially illegally added to herbal-based dietary supplements, ensuring food safety and public health.


Assuntos
Suplementos Nutricionais/análise , Medicamentos de Ervas Chinesas/química , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/tratamento farmacológico , Cromatografia Líquida de Alta Pressão , Suplementos Nutricionais/efeitos adversos , Contaminação de Medicamentos , Medicamentos de Ervas Chinesas/metabolismo , Inocuidade dos Alimentos , Humanos , Limite de Detecção , Masculino , Estrutura Molecular , Citrato de Sildenafila/química , Tadalafila/química , Espectrometria de Massas em Tandem
3.
Int Heart J ; 61(2): 413-418, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32224603

RESUMO

Anticentriole autoantibodies-positive systemic sclerosis (SSc) has been reported to develop pulmonary arterial hypertension (PAH) at a high rate. In this report, we describe two patients with anticentriole antibodies-positive SSc-PAH who were treated with pulmonary vasodilators. Both cases were elderly women with poor physical conditions and clinical findings of SSc. Case 1 was resistant to combination therapy with pulmonary vasodilators; in Case 2, hemodynamic improvement was obtained by upfront combination therapy at an early stage. Because anticentriole antibodies-positive SSc-PAH rapidly deteriorates, careful hemodynamic observation and timely aggressive use of pulmonary vasodilators should be considered.


Assuntos
Anticorpos Antinucleares/imunologia , Centríolos/imunologia , Antagonistas dos Receptores de Endotelina/uso terapêutico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Escleroderma Sistêmico/imunologia , Vasodilatadores/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Bosentana/uso terapêutico , Cateterismo Cardíaco , Quimioterapia Combinada , Epoprostenol/análogos & derivados , Epoprostenol/uso terapêutico , Feminino , Volume Expiratório Forçado , Humanos , Mesilato de Imatinib/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Hipertensão Arterial Pulmonar/diagnóstico por imagem , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/fisiopatologia , Capacidade de Difusão Pulmonar , Pirimidinas/uso terapêutico , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Citrato de Sildenafila/uso terapêutico , Sulfonamidas/uso terapêutico , Tadalafila/uso terapêutico , Tomografia Computadorizada por Raios X
4.
Ann Rheum Dis ; 79(5): 626-634, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32161055

RESUMO

OBJECTIVES: To evaluate initial combination therapy with ambrisentan plus tadalafil (COMB) compared with monotherapy of either agent (MONO), and the utility of baseline characteristics and risk stratification in predicting outcomes, in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and the systemic sclerosis (SSc)-pulmonary arterial hypertension (PAH) subpopulation. METHODS: This post hoc analysis of the Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension (AMBITION) study included patients with CTD-PAH from the modified intention-to-treat population. Time to clinical failure (TtCF) was assessed by baseline characteristics, treatment assignment and risk group (low, intermediate and high) at baseline and week 16. TtCF was compared between groups using Kaplan-Meier curves and Cox proportional hazards regression modelling. RESULTS: The analysis included 216 patients (COMB, n=117; MONO, n=99). The risk of clinical failure was lower with COMB versus MONO (risk reduction: CTD-PAH 51.7%, SSc-PAH 53.7%), particularly in patients with haemodynamic parameters characteristic of typical PAH without features of left heart disease and/or restrictive lung disease at baseline. The risk of clinical failure was lower with COMB versus MONO in the baseline low-risk group (HR not calculated due to no events in COMB), baseline intermediate-risk group (HR 0.519, 95% CI 0.297 to 0.905) and in the week 16 low-risk group (HR 0.069, 95% CI 0.009 to 0.548). CONCLUSIONS: The benefit of COMB over MONO was demonstrated in patients with CTD-PAH, particularly in those with typical PAH haemodynamic characteristics at baseline. COMB is appropriate for patients categorised as low risk and intermediate risk at baseline and low risk at follow-up. TRIAL REGISTRATION NUMBER: NCT01178073.


Assuntos
Fenilpropionatos/administração & dosagem , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/epidemiologia , Piridazinas/administração & dosagem , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/epidemiologia , Tadalafila/administração & dosagem , Adulto , Comorbidade , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/tratamento farmacológico , Doenças do Tecido Conjuntivo/epidemiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Hipertensão Arterial Pulmonar/diagnóstico , Medição de Risco , Escleroderma Sistêmico/diagnóstico , Resultado do Tratamento , Vasodilatadores/administração & dosagem
5.
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 , Metanálise 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
7.
Forensic Sci Int ; 307: 110143, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31931435

RESUMO

The adverse health effects of falsified medicines for erectile dysfunction have been reported in Japan. We purchased tadalafil (Cialis) tablets online and assessed their authenticity and quality. Of the 45 samples we tested, nine were genuine, 23 were falsified, nine were unregistered/unlicensed samples, and the authenticity of four samples could not be ascertained. Observation of packaging and tablet size, weight, and color revealed differences between some genuine and falsified samples. All genuine samples contained the active pharmaceutical ingredient tadalafil at adequate quantities, while falsified samples contained sildenafil (Viagra). Some falsified samples contained insufficient quantities of tadalafil. All unregistered/unlicensed samples contained neither tadalafil nor sildenafil. Some falsified samples did not dissolve/disintegrate sufficiently. The status of most samples was detectable by Raman scattering and near-infrared spectroscopy. Restricting consumer access to falsified medicines can prevent undesirable health effects.


Assuntos
Comércio , Medicamentos Falsificados , Internet , Inibidores da Fosfodiesterase 5/química , Tadalafila/química , Humanos , Japão , Espectroscopia de Luz Próxima ao Infravermelho , Análise Espectral Raman , Comprimidos
8.
Food Chem Toxicol ; 135: 111038, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31825855

RESUMO

The aim of the study was to evaluate the potential protective role of sildenafil and tadalafil in contrast-induced nephropathy (CIN) by modulating oxidative stress. Thirty Wistar male rats were equally assigned into five groups: sham, CIN, CIN + sildenafil (10 mg/kg bw/day), CIN + tadalafil (5 mg/kg bw/day) and CIN + N-Acetyl Cysteine (NAC) (100 mg/kg bw/day) as a positive control. CIN was induced by 12 h dehydration and administration of indomethacin (10 mg/kg bw), N-ω- nitro-L-arginine methyl ester (10 mg/kg bw), and iopromide (3 g/kg bw iodine). Blood was drawn prior to and 24 h after CIN induction for evaluating renal function and oxidative stress. In the CIN group, total antioxidant capacity (TAC), reduced glutathione (GSH) and catalase (CAT) levels were significantly decreased; and protein carbonyl (PROTC) and thiobarbituric reactive species (TBARS) were significantly increased compared to the sham group. Pre- Sildenafil and tadalafil pre-treatment reduced CIN risk and reversed oxidative stress almost to the sham group levels. These results suggest that PDE5Is can be good candidates for preventing CIN based on their ability to modulate the oxidant/antioxidant balance.


Assuntos
Antioxidantes/metabolismo , Meios de Contraste/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Oxidantes/metabolismo , Inibidores da Fosfodiesterase 5/farmacologia , Citrato de Sildenafila/farmacologia , Tadalafila/farmacologia , Acetilcisteína/administração & dosagem , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , Nefropatias/enzimologia , Nefropatias/metabolismo , Masculino , Camundongos , Estresse Oxidativo , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
9.
Theriogenology ; 142: 236-245, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31711694

RESUMO

New methods are being developed for the treatment of benign prostatic hyperplasia (BPH) in dogs. The aim of the present study was to evaluate the effects of Tadalafil on the treatment of experimentally induced BPH in dogs. Twenty-five adult intact male dogs were randomly divided into five groups (n = 5): normal group; dogs induced with BPH and treated with Tadalafil (5 mg/day p.o.); dogs which received Tadalafil (5 mg/day p.o.); dogs induced with BPH and treated with castration; and dogs induced with BPH. For 4 sequential weeks, the hematologic and prostate-specific factors (dihydrotestosterone (DHT), serum prostate-specific antigen (PSA), serum prostatic acid phosphatase (PAP), and canine prostatic specific esterase (CPSE)) were measured. Significant differences were observed in the level of PSA, CPSE, and PAP concentration between the normal vs. BPH-Tadalafil, BPH-castrated, and BPH groups. Treating BPH-induced dogs with Tadalafil or castration significantly declined the serum PSA, CPSE, and PAP levels compared to those of the untreated BPH-induced group. The treatment of normal dogs with Tadalafil did not affect prostate-specific biomarkers in comparison with normal dogs. In conclusion, and according to the prostatic indices, it could be stated that Tadalafil, compared with castration, could be used for the treatment of BPH in dogs.


Assuntos
Orquiectomia , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/cirurgia , Tadalafila/uso terapêutico , Animais , Terapia Combinada , Modelos Animais de Doenças , Doenças do Cão/tratamento farmacológico , Doenças do Cão/patologia , Doenças do Cão/cirurgia , Cães , Masculino , Orquiectomia/veterinária , Hiperplasia Prostática/patologia , Hiperplasia Prostática/veterinária , Resultado do Tratamento
10.
J Pharm Biomed Anal ; 177: 112872, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31525574

RESUMO

It is often reported that falsified medicines have harmful effects on patients both Japan and abroad. In this study, we purchased vardenafil tablets on the internet and investigated their quality and authenticity using visual observations, authenticity investigations, non-destructive tests (handheld NIR and Raman spectroscopy), and quality analyses (active ingredient content and tablet dissolution rate). We used genuine 20-mg Levitra tablets that were sold in Japan and tablets from Bayer AG (Germany) as controls. In April 2015, we obtained 28 samples from 15 websites on the internet. Our authenticity investigations revealed that 11 (40%) were genuine products and 17 (60%) were falsified products. Handheld NIR and Raman results revealed that the falsified products had different spectra to the genuine products. Principal component analysis of the NIR and Raman spectra showed variation among the falsified products. The 11 genuine products were of good quality, and the 17 falsified products were of poor quality. The falsified products contained sildenafil (the active ingredient of Viagra) or tadalafil (the active ingredient of Cialis) instead of vardenafil. Our results show that falsified Vardenafil tablets are sold on the internet and that it is important to prevent illegal internet sales and increase consumer awareness of the presence of falsified medicines.


Assuntos
Medicamentos Falsificados/análise , Disponibilidade de Medicamentos Via Internet/normas , Controle de Qualidade , Agentes Urológicos/análise , Dicloridrato de Vardenafila/análise , Medicamentos Falsificados/química , Medicamentos Falsificados/economia , Humanos , Japão , Disponibilidade de Medicamentos Via Internet/economia , Análise de Componente Principal , Citrato de Sildenafila/análise , Análise Espectral Raman , Comprimidos , Tadalafila/análise , Agentes Urológicos/química , Agentes Urológicos/economia , Agentes Urológicos/normas , Dicloridrato de Vardenafila/química
11.
J Matern Fetal Neonatal Med ; 33(1): 167-170, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29886797

RESUMO

Purpose: The aim of this study is to evaluate the safety of clinical usage of tadalafil in women with preeclampsia.Materials and methods: Maternal, fetal, and neonatal adverse events were closely examined in eight preeclampsia patients receiving tadalafil treatment.Results: There were no maternal adverse events associated with 10 mg/day of tadalafil. Even at 20 mg/day, only grade 1 headaches in two cases and grade 1 palpitation in one case were observed, which resolved spontaneously within 3 days. At a dose of 40 mg/day, there was only one case of grade 1 headache. All these adverse events were grade 1 and spontaneously resolved within 3 days. There were no fetal adverse events. All observed neonatal adverse events were thought to be caused by prematurity and not related to tadalafil.Conclusion: This study shows that tadalafil treatment for preeclampsia is deemed sufficiently tolerable. Although there was a dose-dependent increase in maternal adverse events, all the adverse events were mild and deemed to be safe for the mother and fetus at all dosages.


Assuntos
Pré-Eclâmpsia/tratamento farmacológico , Tadalafila/administração & dosagem , Tadalafila/efeitos adversos , Adulto , Arritmias Cardíacas/induzido quimicamente , Peso ao Nascer/efeitos dos fármacos , Cesárea/estatística & dados numéricos , Relação Dose-Resposta a Droga , Feminino , Cefaleia/induzido quimicamente , Humanos , Gravidez , Resultado da Gravidez , Resultado do Tratamento
12.
Ren Fail ; 41(1): 976-986, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31797710

RESUMO

Objective: The present study assesses whether phosphodiesterase type 5 (PDE-5) inhibitor or carnitine exert nephroprotective effects against clinical contrast-induced nephropathy (CIN).Materials and Methods: The present study consisted of three groups of CKD patients. The first group was control group, who were treated with N-acetyl-L-cysteine 1 day before and on the day of radiocontrast administration. The second one was carnitine group, where the patients were infused with carnitine over 10 min 2 h prior to the radiocontrast administration and 24 h post CT. The third one was PDE-5 inhibitor group, where patients were given tadalafil 2 h prior to the administration of the radiocontrast and in the subsequent day. Urine and blood samples were collected before and at the following time sequence: 2, 6, 12, 24, 48, and 120 h after the contrast administration, for creatinine and NGAL determination.Results: Pretreated with N-acetyl-L-cysteine prior to administration of contrast media (CM) to CKD patients caused a significant increase in urinary but not of plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum creatinine (SCr). In contrast, pretreatment with carnitine prevented the increase in urinary NGAL and reduced SCr below basal levels. Similarly, tadalafil administration diminished the elevation of CM-induced urinary NGAL.Conclusions: These results indicate that carnitine and PDE-5 inhibitors may comprise potential therapeutic maneuvers for CIN.


Assuntos
Carnitina/uso terapêutico , Nefropatias/induzido quimicamente , Inibidores da Fosfodiesterase 5/uso terapêutico , Insuficiência Renal Crônica/complicações , Tadalafila/uso terapêutico , Idoso , Estudos Cross-Over , Feminino , Haptoglobinas/genética , Humanos , Nefropatias/genética , Nefropatias/prevenção & controle , Masculino , Estudos Prospectivos
13.
Acta Cir Bras ; 34(9): e201900901, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800678

RESUMO

PURPOSE: To evaluate the effects of tadalafil (TD) in preventing histological alterations of the corpus cavernosum caused by isolated lesions of cavernous nerve (ILCN) and artery (ILCA) in rats. METHODS: Fifty male Wistar rats were randomly assigned in five groups: G1: control; G2: bilateral ILCN; G3: bilateral ILCA; G4: ILCN+TD; G5: ILCA+TD. The cavernous bodies were submitted to histomorphometry, immunohistochemistry and biochemical analysis. RESULTS: Nerve density was significantly higher in G2 and G4 compared to control (22.62±2.84 and 19.53±3.47 vs. 15.72±1.82; respectively, p<0.05). Smooth muscle density was significantly lower in G2 and G3 in comparison to G1 (12.87±1.90 and 18.93±1.51 vs. 21.78±1.81, respectively; p<0.05). A significant decrease in the sinusoidal lumen area was observed in G2 compared to controls (5.01±1.62 vs. 9.88±3.66, respectively; p<0.05) and the blood vessel density was increased in G2 and G3 (29.32±4.13 e 20.80±2.47 vs. 10.13±2.71, p<0.05). Collagen density was higher in G3 compared to G1 (93.76±15.81 vs. 64.59±19.25; p<0.05). CONCLUSIONS: Histomorphometric alterations caused by ILCN were more intense than those produced by vascular injury, but the collagen analyses showed more fibrosis in animals with ILCA. TD was effective in preventing the majority of the alterations induced by the periprostatic bundle injury.


Assuntos
Pênis/irrigação sanguínea , Pênis/inervação , Traumatismos dos Nervos Periféricos/prevenção & controle , Inibidores da Fosfodiesterase 5/farmacologia , Substâncias Protetoras/farmacologia , Tadalafila/farmacologia , Animais , Colágeno/análise , Colágeno/efeitos dos fármacos , Tecido Elástico/anatomia & histologia , Tecido Elástico/efeitos dos fármacos , Disfunção Erétil/prevenção & controle , Imuno-Histoquímica , Masculino , Pênis/efeitos dos fármacos , Pênis/patologia , Prostatectomia/efeitos adversos , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes
14.
Int J Mol Sci ; 20(23)2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31801292

RESUMO

: Duchenne muscular dystrophy (DMD) is one of the most severe forms of inherited muscular dystrophies. The disease is caused by the lack of dystrophin, a structurally essential protein; hence, a definitive cure would necessarily have to pass through some form of gene and/or cell therapy. Cell- and genetic-based therapeutics for DMD have been explored since the 1990s and recently, two of the latter have been approved for clinical use, but their efficacy is still very low. In parallel, there have been great ongoing efforts aimed at targeting the downstream pathogenic effects of dystrophin deficiency using classical pharmacological approaches, with synthetic or biological molecules. However, as it is always the case with rare diseases, R&D costs for new drugs can represent a major hurdle for researchers and patients alike. This problem can be greatly alleviated by experimenting the use of molecules that had originally been developed for different conditions, a process known as drug repurposing or drug repositioning. In this review, we will describe the state of the art of such an approach for DMD, both in the context of clinical trials and pre-clinical studies.


Assuntos
Reposicionamento de Medicamentos/métodos , Distrofia Muscular de Duchenne/tratamento farmacológico , Fármacos Neuromusculares/uso terapêutico , Prednisona/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Distrofina/deficiência , Distrofina/genética , Gentamicinas/uso terapêutico , Humanos , Metformina/uso terapêutico , Camundongos Transgênicos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patologia , Pregnenodionas/uso terapêutico , Sinvastatina/uso terapêutico , Tadalafila/uso terapêutico , Tamoxifeno/uso terapêutico
15.
Medicine (Baltimore) ; 98(46): e17925, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725644

RESUMO

BACKGROUND: Erectile dysfunction (ED) affects many adult men worldwide. Many studies on the brain of psychogenic ED have shown significant cerebral functional changes and reduced volume of gray matter and white matter microstructural alterations in widespread brain regions. Chaihu-Shugan-San (CHSGS) capsule has been used to treat ED from the 20th century in China. However, clinical research of CHSGS capsule in the treatment of ED was lack. We design this study to evaluate the efficacy and safety of CHSGS capsule in the treatment of patients suffering from psychogenic ED. Furthermore, we also aim to provide a new evidence as well as an innovation of the clinical treatment in psychogenic ED. METHODS: This study is designed as a multi-center, 3-arms, randomized trial. From the perspective of psychogenic ED, we will divide patients into 3 groups, which are placebo group, tadalafil group and CHSGS group. One hundred thirty-five patients will be randomly allocated to receive placebo, CHSGS capsule or tadalafil oral pharmacotherapy. After the period of 4-week treatment, the outcome of primary assessment changes in the brain MRI, IIEF-5, EHS, and QEQ total scores from baseline. Secondary assessments include the SEAR, HAMA-14, HAMD-17 scores, response rate of the patients and their partners. DISCUSSION: We designed this study based on previous research about psychogenic erectile dysfunction (ED). This study will provide objective evidences to evaluate the effects of CHSGS capsule as an adjuvant treatment for psychogenic ED. TRIAL REGISTRATION NUMBER: chictr.org.cn, ChiCTR-IOR-1800018301.


Assuntos
Disfunção Erétil/terapia , Extratos Vegetais/uso terapêutico , Tadalafila/uso terapêutico , Vasodilatadores/uso terapêutico , Adulto , Método Duplo-Cego , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Tadalafila/administração & dosagem , Tadalafila/efeitos adversos , Vasodilatadores/administração & dosagem , Vasodilatadores/efeitos adversos , Adulto Jovem
16.
J Pharmacol Sci ; 141(4): 131-138, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31734027

RESUMO

Oxaliplatin, a platinum-based chemotherapeutic drug, frequently induces peripheral neuropathy. Accumulating evidences suggest a possible relationship between peripheral vascular impairment and peripheral neuropathy. In this study, we investigated the effects of vasodilators on cumulative peripheral neuropathy induced by repeated injections of oxaliplatin (10 mg/kg) once a week for 8 weeks in mice. Single injections of vasodilators, including a phosphodiesterase type 5 inhibitor tadalafil acutely alleviated oxaliplatin-induced cold hypersensitivity, while tadalafil had no effect on the mechanical hypersensitivity. By contrast, long-term administration of tadalafil (0.1% in chow diets) during the oxaliplatin injection period reduced the oxaliplatin-induced decreases in skin temperature and blood flow without affecting platinum concentrations in blood, sciatic nerves, and dorsal root ganglion. The long-term administration significantly suppressed cold, mechanical, and electrical current hypersensitivities as well as thermal hypoesthesia. Furthermore, it prevented the decreases in sensory nerve conductance velocity and the number of endoneurial microvessels, and axon degeneration in the sciatic nerves. In vitro studies confirmed that tadalafil does not interfere with the cytotoxicity of oxaliplatin against human cancer cell lines. Altogether, these results suggest that improvement of peripheral vascular impairment by tadalafil could alleviate and prevent oxaliplatin-induced peripheral neuropathy.


Assuntos
Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Tadalafila/uso terapêutico , Lesões do Sistema Vascular/tratamento farmacológico , Vasodilatadores/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Gânglios Espinais/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Nervo Isquiático/efeitos dos fármacos , Pele/efeitos dos fármacos
17.
Nihon Yakurigaku Zasshi ; 154(5): 259-264, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31735755

RESUMO

Chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) is commonly diagnosed in men younger than 50 years old. It is characterized by pelvic pain, voiding symptoms and sexual dysfunction. The considerable discomfort or pain experienced has a negative impact on the quality of life of patients and is a huge economic burden because of the high recurrence rate and the low cure rate. Appropriate animal models are essential for the development of new drugs for the treatment of CP/CPPS, and several rodent models induced by different methods and over different time frames have been established. This article reviews studies of three in vivo rodent models of prostatitis, namely, chemical-induced, autoimmune-induced and hormone-associated models reported by us and other investigators. Recent clinical investigation has suggested that tadalafil improves the International Prostatic Symptom Score and the total National Institutes of Health Chronic Prostatitis Symptom Index score of patients with benign prostatic hyperplasia with CP/CPPS, which enables us to investigate the effect of tadalafil on the pelvic-pain-related behavior and prostatic inflammation in two of these prostatitis model types, experimental autoimmune prostatitis (EAP) and hormone/castration-induced prostatitis (HCP). Both models showed the pelvic-pain-related behavior and prostatic inflammation that are characteristic of chronic prostatitis. In EAP, tadalafil suppressed both the pelvic-pain-related behavior and the prostatic inflammation. In HCP, tadalafil suppressed the pelvic-pain-related behavior. These results mimic the clinical findings. Therefore EAP and HCP are suitable for the evaluation of the potency of drugs for the treatment of CP/CPPS.


Assuntos
Dor Crônica/tratamento farmacológico , Dor Pélvica/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Prostatite/complicações , Tadalafila/uso terapêutico , Animais , Modelos Animais de Doenças , Humanos , Masculino , Roedores
18.
Acta Med Indones ; 51(3): 275-281, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31699953

RESUMO

BACKGROUND: Tadalafil is a PDE5I which has been licensed for the treatment of erectile dysfunction (ED) since 2003, is effective from 30 minutes after administration and its efficacy is maintained for up to 36 hours. More recently, it is also given OAD in a lower dose to allow spontaneous sexual activities. However, whether OAD administration is more effective than PRN administration in improving the EF is yet to be established. This study aimed to evaluate whether OAD administration of tadalafil leads to a better improvement of erectile function (EF) in patients with erectile dysfunction (ED) compared to PRN administration. METHODS: literature search of electronic database was performed through Medline, Scopus, Cochrane Library, and CINAHL databases. Cochrane Risk of Bias Tool was then employed to assess the risk of bias in each study. RESULTS: initial literature search resulted in 231 hits, but only four studies were included in final selection. Based on our judgements, the study by Kang et al. was the most applicable in our clinical setting. This study showed that subjects who received tadalafil OAD had statistically significant higher increases of mean IIEF-EF (6.5 (SD 4.5) vs 4.9 (SD 4.2), p=0.032), proportion of "yes" responses to SEP-2 (81.8% vs 64.7%, p=0.025), and proportion of "yes" responses to SEP-3 (77.3% vs 60.3%, p=0.034). CONCLUSION: administration of tadalafil OAD leads to a better improvement of EF compared to PRN administration.


Assuntos
Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Tadalafila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
19.
Mo Med ; 116(5): 400-403, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31645793

RESUMO

Intracerebral hemorrhage occurs when a diseased blood vessel within the brain bursts. We present a case of 69-year-old patient with two sequential episodes of lobar intracerebral hemorrhage occurring during sexual intercourse. Both episodes were associated with the use of phosphodiesterase-5 inhibitors. This is the first case reported which is temporally associated with isolated bilateral lobar bleeds with appropriate use of phosphodiesterase-5 inhibitor on two different occasions associated with sexual intercourse.


Assuntos
Hemorragia Cerebral/etiologia , Inibidores da Fosfodiesterase 5/efeitos adversos , Citrato de Sildenafila/efeitos adversos , Tadalafila/efeitos adversos , Idoso , Hemorragia Cerebral/diagnóstico por imagem , Coito , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Inibidores da Fosfodiesterase 5/administração & dosagem , Citrato de Sildenafila/administração & dosagem , Tadalafila/administração & dosagem , Tomografia Computadorizada por Raios X
20.
Ginekol Pol ; 90(9): 513-519, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588548

RESUMO

OBJECTIVES: The aim of this study was to compare the effects of sildenafil, vardenafil and tadalafil in treatment for ischemia/reperfusion injury which is created experimentally in rat ovaries. MATERIAL AND METHODS: For this study, 30 female Wistar albino rats were used, and the rats were separated randomly intofive groups consisting of six rats each: normal, torsion-detorsion, torsion-detorsion + sildenafil 1.4 mg/kg, torsion-detorsion+ vardenafil 1.7 mg/kg and torsion-detorsion + tadalafil 5.0 mg/kg. The agents were given intraperitoneally 30 minutesbefore detorsion. An ovarian torsion procedure was implemented in all other groups for 3 hours with the exception of thenormal group. Then, a detorsion procedure was implemented to the groups for 3 hours. RESULTS: The sildenafil and vardenafil treatments showed protective effect by preventing significant increase in inflammationparameters. (p = 0.058, 0.138). The tadalafil treatment was only protective for cellular degeneration (p = 0.140). Thevardenafil treatment was protective for edema (p = 0.238), vascular congestion (p = 0.111), inflammation (p = 0.138) andcellular degeneration (p = 0.532). Sildenafil, vardenafil and tadalafil inhibited the increase of atretic follicle. AMH levels werestatistically different between torsion and detorsion and vardenafil group (p = 0.004, 0.004), whereas tadalafil and sildenafilgroups were similar to normal group (p = 0.108, 0.108). CONCLUSIONS: PDE inhibitors were found to be effective in reducing ovarian ischemia/reperfusion injury. Sildenafil andtadalafil seem to be more effective than the vardenafil in protecting the ovarian reserve.


Assuntos
Ovário/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/patologia , Citrato de Sildenafila/farmacologia , Tadalafila/farmacologia , Dicloridrato de Vardenafila/farmacologia , Animais , Feminino , Doenças Ovarianas/patologia , Ovário/patologia , Ratos , Ratos Wistar , Anormalidade Torcional/patologia
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