Effect of a novel phosphodiesterase type 5 inhibitor, CPD1, on paraquat-induced lung fibrosis in rats / 中国药理学通报

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on lung pathological phenotype and epithelial-mesenchymal transition of alveolar epithelial cells in lung fibrosis model rats caused by paraquat (PQ). Methods Lung fibrosis model was constructed by a single intraperitoneal injection of PQ (30 mg·kg

Effect of a novel phosphodiesterase type 5 inhibitor,CPD1,on unilateral renal interstitial fibrosis caused by ureteric obstruction in mice / 中国药理学通报

Aim To investigate the effects of CPD1,a novel phosphodiesterase 5 inhibitor,on renal pathological phenotype and fibrotic protein expression in renal fibrosis model mice. Methods Male C57BL/6 J mice were divided into three groups randomly(sham group,UUO group and UUO+CPD1 group). Unilateral ureteric obstruction model was constructed by surgery,and CPD1(5 mg·kg-1·d-1)was administered by intragastric administration two hours after the modeling for seven days. HE and Sirius Red staining were used to observe the distribution of tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of fibronectin(FN),α-SMA,collagen-I and kidney injury molecule-1(Kim-1). Results Compared with sham operation group,the renal tubules of mice were dilated and accompanied by a large amount of inflammatory infiltration. Moreover,the expressions of FN,α-SMA,collagen-I and Kim-1 proteins increased significantly(P<0.05)in UUO group. CPD1 treatment improved the kidney structure and decreased the expression of collagen fibers. Furthermore,CPD1 inhibited the expression of FN,α-SMA,collagen-I and Kim-1 markedly(P<0.05). Conclusions Phosphodiesterase 5 inhibitor CPD1 alleviates the progression of renal fibrosis induced by unilateral ureteral obstruction through down-regulating ECM deposition in the extracellular matrix and expression of Kim-1. The specific mechanism remains to be further studied.

Effect of a novel phosphodiesterase type 5 inhibitor, CPD1, on carbon tetrachloride-induced liver fibrosis in mice / 中国药理学通报

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on liver pathological phenotype and hepatic stellate cells (HSCs) activation in hepatic fibrosis model mice caused by carbon tetrachloride ( CCl

Efficacy and safety of phosphodiesterase type 5 inhibitors and selective serotonin reuptake inhibitors in the treatment of comorbiditiy of erectile dysfunction and premature ejaculation: a meta analysis / 现代泌尿外科杂志

【Objective】 To evaluate the efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors alone or in combination with selective serotonin reuptake inhibitors (SSRIs) compared with SSRIs alone in the treatment of comorbidity of erectile dysfunction (ED) and premature ejaculation (PE). 【Methods】 The clinical randomized controlled trials of ED and PE comorbidity treated with PDE5 inhibitors alone or in combination with SSRIs were searched from database inception to Sep.2022, in CNKI, PubMed, Web of Science, Embase, Wanfang Database, cqVIP Database, SinoMed and Yiigle. The intravaginal ejaculatory latency time(IELT), score of International Index of Erectile Function 5 (IIEF-5) and adverse reaction rate were analyzed with RevMan 5.4.1 software. 【Results】 A total of9 studies involving 793 patients were included. Meta analysis showed that compared with SSRIs alone, PDE5 inhibitors alone or in combination with SSRIs yielded better results in IELT [MD=1.99, 95%CI(1.51-2.46), P<0.001] and higher IIEF-5 score [MD=4.61, 95%CI(3.68-5.55), P<0.001] , but no increase in adverse events [RR=0.99, 95%CI(0.74-1.31), P=0.92] . 【Conclusion】 In the treatment of ED and PE comorbidity, priority should be given to ED or both ED and PE, which can produce better efficacy without increasing the adverse effects.

Efficacy and safety of kidney -tonifying Chinese patent medicine combined with PDE 5 inhibitor in the treatment of erectile dysfunction ：a network meta -analysis / 中国药房

OBJECTIVE To systematically review the efficacy and safety of kidney -tonifying Chinese patent medicine combined with phosphodiesterase type 5（PDE5）inhibitors in the treatment of erectile dysfunction （ED），and to provide evidence - based reference for clinical medication . METHODS Retrieved from PubMed ，Embase，Cochrane Library ，Web of Science ，VIP， China Biomedical Literature Database ，CNKI and Wanfang database ，randomized controlled trials （RCTs）of kidney -tonifying Chinese patent medicine combined with PDE 5 inhibitors（trial group ）versus PDE 5 inhibitors or kidney -tonifying Chinese patent medicine alone （control group ）were collected . The search period was from the establishment of the database to February 15，2022. After literature screening and data extraction ，the risk of bias assessment tool recommended in Cochrane System Reviewer ’s Handbook 6.1.0 was used to evaluate the quality of the included literature ；Stata 16.0 software was used for network meta -analysis； and the funnel plot was used for publication bias analysis . RESULTS A total of 23 RCTs were included ，with a total of 2 417 patients， involving 8 kinds of Chinese patent medicines ， including Congrong yishen granule ，Canrong zhutian capsule ， Compound xuanju capsule ， Huanshao capsule ， Shanhaidan granule， Shengjing capsule ， Shisanwei ziyin zhuangyang capsule，Shugan yiyang capsule . The results of network meta analysis showed that in terms of total effective rate ，Compound xuanju capsule combined with PDE 5 inhibitor，Shengjing capsule combined with PDE 5 inhibitor，Shugan yiyang capsule combined with PDE 5 inhibitor had higher total effective rate ；in terms of international index of erectile function 5，the scores of Compound xuanju capsule combined with PDE 5 inhibitor，Congrong yishen granule combined with PDE 5 inhibitor，and Canrong zhutian capsule combined with PDE 5 inhibitor were higher ；in terms of safety ，the incidence of adverse drug reactions caused by Huanshao capsule ，Shanhaidan granule and Shugan yiyang capsule were lower . CONCLUSIONS Kidney-tonifying Chinese patent medicine combined with PDE 5 inhibitor can improve the erectile function of ED patients and reduce the occurrence of adverse drug reactions . In terms of efficacy and safety ，Compound xuanju capsule combined with PDE 5 inhibitor is the best .

Mechanism of Yiyuan Qiwei Pills in Treatment of Diabetes Mellitus-induced Erectile Dysfunction / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effect of Yiyuan Qiwei pills （YYQW） on diabetes mellitus-induced induced erectile dysfunction （DMED） in rats and explore its regulation on the nitric oxide （NO）-cyclic guanosine monophosphate （cGMP） signaling pathway. MethodFifty-five healthy SD male rats of clean grade aged 2-3 months underwent intraperitoneal injection of streptozotocin （STZ） to induce the DMED model， and another 10 healthy SD male rats of clean grade aged 2-3 months were assigned to the control group. The model rats were randomly divided into a model group， a sildenafil group （5 mg·kg-1， ig）， and low-， medium-， and high-dose YYQW groups （1.5， 3.0， 6.0 g·kg-1， ig）. The rats in the model group and the control group were given normal saline by gavage at 10 mL·kg-1， once a day for two months. After intervention， the penile erectile function of rats in each group was measured by a pressure detection system. The pathological changes and ultrastructure of penile corpus cavernosum were observed by hematoxylin-eosin （HE） staining and transmission electron microscopy， respectively. The level of NO in the corpus cavernosum was detected by nitrate reductase. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of cGMP and advanced glycation end products （AGEs）. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of endothelial nitric oxide synthase （eNOS）， neurogenic nitric oxide synthase （nNOS）， total nitric oxide synthase （NOS）， and phosphodiesterase type5 （PDE5） in rat penile tissues. The expression of above proteins was detected by Western blot. ResultCompared with the control group， the model group showed decreased intracavernous pressure （ICP）， NO， and cGMP levels， reduced mRNA and protein expression of nNOS and NOS， and increased PDE5 mRNA and protein expression （P<0.05）. Compared with the model group， the sildenafil group and the YYQW groups displayed increased ICP， NO， and cGMP levels， elevated mRNA and protein expression levels of nNOS and NOS， and reduced PDE5 mRNA and protein expression levels （P<0.05）. There were no pathological changes in the tissues and cell ultrastructure of the corpus cavernosum in the control group， while serious pathological changes were observed in the model group. Additionally， the sildenafil group and the YYQW groups were superior to the model group， the optimal effect was observed in the high-dose YYQW group. ConclusionYYQW can improve the penile erectile function of DMED rats and reduce the pathological damage of corpus cavernosum. The mechanism may be related to the promotion of nNOS and NOS expression， the inhibition of PDE5 expression， and the activation of the NO/cGMP signaling pathway.

Mechanism of Yiyuan Qiwei Pills in Treatment of Diabetes Mellitus-induced Erectile Dysfunction / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effect of Yiyuan Qiwei pills （YYQW） on diabetes mellitus-induced induced erectile dysfunction （DMED） in rats and explore its regulation on the nitric oxide （NO）-cyclic guanosine monophosphate （cGMP） signaling pathway. MethodFifty-five healthy SD male rats of clean grade aged 2-3 months underwent intraperitoneal injection of streptozotocin （STZ） to induce the DMED model， and another 10 healthy SD male rats of clean grade aged 2-3 months were assigned to the control group. The model rats were randomly divided into a model group， a sildenafil group （5 mg·kg-1， ig）， and low-， medium-， and high-dose YYQW groups （1.5， 3.0， 6.0 g·kg-1， ig）. The rats in the model group and the control group were given normal saline by gavage at 10 mL·kg-1， once a day for two months. After intervention， the penile erectile function of rats in each group was measured by a pressure detection system. The pathological changes and ultrastructure of penile corpus cavernosum were observed by hematoxylin-eosin （HE） staining and transmission electron microscopy， respectively. The level of NO in the corpus cavernosum was detected by nitrate reductase. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of cGMP and advanced glycation end products （AGEs）. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of endothelial nitric oxide synthase （eNOS）， neurogenic nitric oxide synthase （nNOS）， total nitric oxide synthase （NOS）， and phosphodiesterase type5 （PDE5） in rat penile tissues. The expression of above proteins was detected by Western blot. ResultCompared with the control group， the model group showed decreased intracavernous pressure （ICP）， NO， and cGMP levels， reduced mRNA and protein expression of nNOS and NOS， and increased PDE5 mRNA and protein expression （P<0.05）. Compared with the model group， the sildenafil group and the YYQW groups displayed increased ICP， NO， and cGMP levels， elevated mRNA and protein expression levels of nNOS and NOS， and reduced PDE5 mRNA and protein expression levels （P<0.05）. There were no pathological changes in the tissues and cell ultrastructure of the corpus cavernosum in the control group， while serious pathological changes were observed in the model group. Additionally， the sildenafil group and the YYQW groups were superior to the model group， the optimal effect was observed in the high-dose YYQW group. ConclusionYYQW can improve the penile erectile function of DMED rats and reduce the pathological damage of corpus cavernosum. The mechanism may be related to the promotion of nNOS and NOS expression， the inhibition of PDE5 expression， and the activation of the NO/cGMP signaling pathway.

Effect of a novel phosphodiesterase type 5 inhibitor, CPD1, on vasoconstriction in rats with pulmonary arterial hypertension / 中国药理学通报

Aim To investigate the effect of CPD1 , a novel phosphodiesterase 5 inhibitor, on contractile ten- sion of pulmonary artery and aorta in rats with pulmonary arterial hypertension ( PAH ) .Methods MCT- induced PAH was generated by a single intraperitoneal injection of MCT(50 mg • kg"1) in rats.Seven days after MCT injection, the rats were treated with CPD1 ( 10 mg • kg-1 • d"1) for 14 days.The tension of vascular rings was examined in MCT-induced PAH rats.Results MCT treated rats exhibited profound PAH when examined 3 weeks after injection.In contrast, gavage administration of CPD1 led to significant decrease in the right ventricle systolic pressure ( RVSP) and right ventricular mass index (RVMI), as well as MCT-induced pulmonary arterial wall thinning and enlarged lumen, indicating that CPD1 inhibited the de- velopment of PAH.Cavage administration of CPD1 also reduced phenylephrine and endothelin-1-induced pulmonary artery contraction and aorta contraction in MCT-treated rats.Conclusions Treatment with CPD1 attenuates vascular reactivity, lessens vascular smooth muscle cell proliferation and remodeling, and inhibits PAH via inhibition of non-voltage dependent Ca2∗ channels in normal and PAH rats.

Medida computadorizada da evolução da área cicatricial tratada com ultrassom terapêutico e citrato de sildenafila / Computerized measurement of the evolution of cicatricial area treated with ultrasound and sildenafil citrate

Objetivou-se comparar a evolução da cicatrização de feridas cirúrgicas com cinco protocolos de tratamento através de análise planimétrica. Grupos de 12 ratos Wistar, foram alocados em cinco estudos experimentais: A- controle negativo; B- ferida cirúrgica, tratada com ultrassom terapêutico (UST) desligado ; C- ferida tratada somente com citrato de sildenafila ; D- ferida tratada com citrato de sildenafila e UST e grupo E-ferida tratada somente com UST. A evolução cicatricial foi acompanhada diariamente e avaliada por imagem fotográfica computadorizada aos sete, 14 e 21 dias. A aplicação do UST pulsado, com doses 1MHZ e 0,4Wcm2 reduziu o tempo de cicatrização epitelial em condições experimentais, favorecendo precocemente a reparação tecidual com efeitos qualitativos superiores ao tratamento com citrato de sildenafila (CS). A mensuração computacional para evolução da cicatrização de ferida dérmica mostrou-se um recurso de fácil aplicação sendo de baixo custo e eficiente para a aplicabilidade na rotina médica veterinária.

This study aimed at comparing the evolution of healing of surgical wounds with five treatment protocols through planimetric measurement. Groups of 12 Wistar rats were allocated in five experimental studies: A ­ negative control; B ­ surgical wound treated with therapeutic ultrasound turned off; C ­ surgical wound treated with sildenafil citrate; D ­ wound treated with sildenafil citrate and therapeutic ultrasound; and group E ­ wound treated only with therapeutic ultrasound. The healing progress was monitored daily and assessed by computed photographic image at seven, 14 and 21 days. It was concluded that the application of pulsated therapeutic ultrasound on surgical wounds at 1 MHz and 0.4Wcm2 doses reduces the epithelial healing time in experimental conditions, favoring the early repair of tissue with qualitative effects superior than the ones found in the treatment with sildenafil citrate (SC). The computational measurement for the evolution of the dermal wound healing proved to be an easy-to-apply resource, with a low cost and great efficiency for the applicability in the veterinary medical routine.

Positive outcomes of phosphodiesterase type 5 inhibitor on histopathologic and biochemical changes induced by ureteral obstruction

SUMMARY OBJECTIVES: We examined the effects of tadalafil, one of the phosphodiesterase type 5 (PDE5) inhibitors, in a rat model of with partial and complete unilateral ureteral obstruction (UUO). METHODS: The rats were divided into 5 groups: sham (n=6), partial unilateral ureteral obstruction (PUUO, n=6), PUUO with tadalafil treatment (PUUO+T; Cialis, 10 mg/72 h, intragastric; Lilly, Indianapolis, Indiana, USA), complete unilateral ureteral obstruction (CUUO, n=6), and CUUO with tadalafil treatment (CUUO+T). RESULTS: Fifteen days after the UUO, the ureter presented changes in the layers of urothelium and significant infiltration of inflammatory cells in the PUUO and CUUO groups. Compared with the sham, PUUO and CUUO groups had severe increased inflammatory cell infiltration. The urothelial epithelium exhibited cell degeneration and loss because of the swollen, atrophic, and denuded epithelial cells in the PUUO and CUUO groups. In the PUUO+T and CUUO+T groups, the urothelium revealed less epithelial cell degeneration and loss. The expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) exhibited up-regulation in the PUUO and CUUO groups. The expression of TGF-β decreased positively correlated with that of α-SMA in the tadalafil therapy groups, PUUO+T and CUUO+T. CONCLUSION: The phosphodiesterase type 5 inhibitor's tadalafil reduced expressions of α-SMA and TGF-β in the obstructed ureters, measured by biochemical examinations. In addition, tadalafil decreased urothelium degeneration due to the decreased epithelial cell loss and inflammatory cell infiltration. Our results show that tadalafil prevents or slows down the onset of ureter inflammation and urothelial degeneration in rats with UUO.

RESUMO OBJETIVOS: Examinamos os efeitos do tadalafil em um dos inibidores da fosfodiesterase tipo 5 (PDE5) em um modelo de rato com obstrução ureteral unilateral parcial e completa (UUO). MÉTODOS: Os ratos foram divididos em cinco grupos: sham (n = 6), obstrução ureteral unilateral parcial (PUUO, n = 6), PUUO com tadalafil (PUUO T; Cialis, 10 mg/72 h, intragástrica; Lilly, Indianapolis, Indiana, EUA), completa obstrução ureteral unilateral (CUUO, n = 6) e CUUO com tratamento com tadalafil (CUUO T). RESULTADOS: Quinze dias após a UUO, o ureter apresentou alterações nas camadas de urotélio e infiltração significativa de células inflamatórias nos grupos PUUO e CUUO. Em comparação com os grupos sham, PUUO e CUUO, houve um aumento grave da infiltração de células inflamatórias. O epitélio urotelial exibiu degeneração e perda celular devido às células epiteliais inchadas, atróficas e desnudas nos grupos PUUO e CUUO. Nos grupos PUUO T e CUUO T, o urotélio revelou menor degeneração e perda de células epiteliais. Nós mostramos que a expressão da actina do músculo liso-α (α-SMA) e do fator de crescimento transformador-β (TGF-β) foram exibidas como sub-regulação nos grupos PUUO e CUUO. A expressão do TGF-β foi diminuída positivamente correlacionada com a da α-SMA nos grupos de terapia com tadalafil, PUUO T e CUUO T. CONCLUSÃO: O tadalafil do inibidor da fosfodiesterase tipo 5 reduziu as expressões α-SMA e TGF-β nos ureteres obstruídos, medidos por exames bioquímicos. Além disso, o tadalafil diminuiu a degeneração do urotélio devido à diminuição da perda de células epiteliais e da infiltração de células inflamatórias. Nossos resultados mostram que o tadalafil previne ou retarda o início da inflamação do ureter e degeneração urotelial em ratos com UUO.

Effect of phosphodiesterase type 5 inhibitors on prostate cancer / 国际外科学杂志

Erectile dysfunction was one of the most frequently postoperative complications after radical prostatectomy,which has been deeply concentrated by patients and urologists,along with more and more people were diagnosed as localized prostate cancer.Widely being used for erectile dysfunction after radical prostatectomy,the efficacy and safety of phosphodiesterase type 5 inhibitors have been confirmed by many clinical studies.However,the influences of phosphodiesterase type 5 inhibitors on the occurrence and progression of cancer are still not completely revealed at present.Additionally,the efficiency of phosphodiesterase type 5 inhibitors on biochemical recurrence after radical prostatectomny is still controversial,though it has been demonstrated that phosphodiesterase type 5 inhibitors is not associated with the occunrence of prostate cancer based on recent clinical studies.We will review the possibly mechanisms of phosphodiesterase type 5 inhibitors in oncologic occurrence,especially in the occurrence of prostate cancer and its biochemical recurrence after radical prostatectomy.

Quercetin Relaxed the Smooth Muscle of Rabbit Penile Corpus Cavernosum by Activating the NO-cGMP Signaling Pathway

The aim of this study was to investigate the effect and action mechanism of quercetin on penile corpus cavernosum smooth muscle (PCCSM). PCCSM precontracted with phenylephrine (Phe) was treated with four different concentrations of quercetin (10−7, 10−6, 10−5 and 10−4 M). PCCSM were preincubated with N-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) to block nitric oxide synthase and guanylate cyclase, respectively. The changes in PCCSM tension were recorded, and cyclic nucleotides in the perfusate were measured by radioimmunoassay. The interactions of quercetin with phosphodiesterase type 5 inhibitors (PDE5-Is) such as sildenafil, udenafil and mirodenafil, were also evaluated. PCCSM relaxation induced by quercetin occurred in a concentrationdependent manner. The application of quercetin to PCCSM pre-treated with L-NAME and ODQ significantly inhibited the relaxation. Quercetin significantly increased cGMP in the perfusate. Furthermore, quercetin enhanced PDE5-Is-induced relaxation of PCCSM. Quercetin relaxed the PCCSM by activating the NO-cGMP signaling pathway, and it may be a therapeutic candidate or an alternative treatment for patients with erectile dysfunction who do not completely respond to PDE5-Is.

Advances in the concept of treatment of erectile dysfunction / 中华男科学杂志

Erectile dysfunction (ED) seriously influences the quality of life of the patients and their partners. There are various methods for the treatment of ED, with medication as the first choice. This paper reviews the advances in the concept of treatment of ED, including regular treatment, maximal therapeutic effects, primary diseases inducing ED, and humanistic environment and ideal goal of ED treatment, aiming to help further understand the therapeutic concept and improve clinical management of the disease.

Effects of obstructive sleep apnea and its treatment over the erectile function: A systematic review / 亚洲男科学杂志(英文版)

Erectile dysfunction (ED) is considered a condition with a broad range of etiologies. Obstructive sleep apnea (OSA) syndrome is one of the lesser studied risk factors for ED. We intend to summarize the current evidence on the relationship between OSA and sexual impairment, focusing on the results in terms of erectile function of the different therapies offered to OSA patients. A systematic review was conducted, selecting articles related to the physiology of OSA and ED, and to the treatments of OSA syndrome and their reported outcomes in erectile and sexual function. Higher prevalences of ED in the OSA groups have been published. However, whether this effect on the erectile function occurs in the entire range of OSA severities remains unclear. Several hypotheses were proposed to explain the physiology of this association. Continuous Positive Airway Pressure as a treatment for OSA patients with ED has achieved a significative improvement in the sexual parameters in most of the studies. Phosphodiesterase type 5 inhibitors (iPDE5) on demand are useful as a treatment for ED in this subgroup of patients, with high satisfaction rates. The surgical treatment for the OSA evidenced benefits over the erectile function, and the effect on the sexual satisfaction of the therapy using Mandibular Advancement Devices is still undefined.

A randomized clinical trial investigating treatment choice in Chinese men receiving sildenafil citrate and tadalafil for treating erectile dysfunction / 亚洲男科学杂志(英文版)

Sildenafil and tadalafil are efficacious and well tolerated in Chinese men with erectile dysfunction (ED). Recent study results indicate that men with ED in China who were naïve to phosphodiesterase inhibitor type 5 (PDE5) therapy prefer tadalafil 20-mg (on-demand) versus sildenafil 100-mg (on-demand). Differences in psychosocial outcomes may help to explain treatment preference in favor of tadalafil. This open-label, randomized, crossover study compared psychosocial outcomes and drug attribute choices between tadalafil and sildenafil in Chinese men with ED naïve to PDE5 inhibitor therapy. Eligible patients were randomized to sequential 20-mg tadalafil/100-mg sildenafil (n = 190) or 100-mg sildenafil/20-mg tadalafil (n = 193) for 8 weeks each and were asked which treatment they preferred to take for the 8-week extension phase. Psychosocial outcomes were assessed using the Psychological and Interpersonal Relationship Scale (PAIRS), Drug Attributes Questionnaire (DRAQ), and Sexual Life Quality Questionnaire (SLQQ). When taking tadalafil versus sildenafil, men had a higher mean endpoint score on the PAIRS Spontaneity Domain (tadalafil = 2.86 vs sildenafil = 2.72; P < 0.001), and a lower mean endpoint score on the Time Concerns Domain (tadalafil = 2.41 vs sildenafil = 2.55; P < 0.001). A numerical increase in the Sexual Self-Confidence Domain was observed when taking tadalafil versus sildenafil (tadalafil = 2.76 vs sildenafil = 2.72; P = 0.102). The most frequently chosen drug attributes explaining treatment preference were able to get an erection long after having drug, and ability to get an erection every time. SLQQ results were comparable between treatment groups. These psychosocial outcomes may explain why more Chinese men preferred tadalafil versus sildenafil for the treatment of ED in this clinical trial.

Efeitos cistométricos da castração hormonal e administração diária de tadalafila emcamundongos com hiperatividade detrusora induzida pela deficiência crônica de óxido nítrico

Sintomas do trato urinário inferior (STUI) representam uma das queixas mais comuns em homens. Diferentes distúrbios da micção podem resultar em STUI. Hipogonadismo é umadoença comum e subdiagnosticada no idoso, podendo estar associado a STUI. O objetivodeste estudo foi avaliar os efeitos da administração crônica da Tadalafila em camundongos hipogonádicos com deficiência crônica de óxido nítrico através de estudo cistométrico in vivo. Para tanto, foi comparado a resposta da Tadalafila em animais castrados(hipogonádicos) e após reposição de testosterona (normogonádicos). Um total de quarenta edois camundongos foram randomizados em seis grupos. Grupo 1(L-NAME): L-NAME(60mg/kg), que é um inibidor da síntese da óxido-nítrico sintase, foi administrado em água debeber. Grupo 2 (DTAD): L-NAME (60mg/kg) + diluente da Tadalafila (goma xantana emanitol). Grupo 3 (TAD): L-NAME (60mg/kg) + Tadalafila diário (4mg/kg). Grupo 4(ORQ): L-NAME (60mg/kg) + orquiectomia...

Lower Urinary Tract Symptoms (LUTS) represents one of the most commonly complaints in male. Several voiding disorders can be involved in the pathogenesis of LUTS. Hipogonadism is a common and underdiagnoseddisease in the aging male, usually presenting simultaneously with LUTS. The objective of thisstudy wasto evaluate the cystometric effects of chronic tadalafil administration in castrated micewith nitric oxide cronic deficiency.The results of tadalafiladministration were compared in castrated mice (hypogonadics) and after testosterone replacement (eugonadics). A total of 42 mice were randomized to six groups. Group 1 (L-NAME): L-name (60mg/kg), which is an oxide-nitric sintethase inhibitor, was administrated in drinking water. Group 2 (DTAD): L-name (60mg/kg) + diluent of tadalafil (mannitol and xantane gum). Group 3 (TAD): L-name + daily tadalafil (4mg/kg). Group 4 (ORQ): L-name + orchiectomy...

Efeito da associação da tadalafila com a tansulosina no trato urinário inferior de ratos e de humanos

Recentemente, foi observado que pacientes com DE tratados com inibidores da fosfodiesterase tipo 5 ( I PDE5) melhoram não somente a ereção, mas também os sintomas do trato urinário inferior (STUI). A fisiopatologia dos STUI é desconhecida e há um número crescente de estudos que objetiva compreender suas bases fisiopatológicas. Entretanto, a despeito do conhecimento que existe sobre a melhora dos STUI, não se sabe se IPDE - 5 atua durante o armazenamento, esvaziamento ou ambos. Não se tem conhecimento se a associação do IPDE - 5 com alfabloqueador é melhor que o uso isolado e se esta associação é segura. O objetivo deste estudo foi avaliar a segurança da associação da tansulosina com tadalafila tomados diariamente, bem como seu efeito no trato urinário inferior de humanos e de ratos por meio de estudo urodinâmico METODO: f oi realizado um estudo experimental utilizando ratos com obstrução infra - vesical crônica, induzida por L - NAME e um estudo clínico randomizado, duplo - cego e placebo - controlado durante o período de outubro de 2010 a janeiro de 2012. No estudo experimental, os animais foram distribuídos em 05 grupos; Grupo 1: seis ratos foram tratados sem medicação; Grupo 2: seis ratos foram tratados com L - NAME, na dose oral de 60 mg/Kg/dia; Grupo 3: seis ratos foram tratados com L - NAME e tansulosina (1mg/kg); Grupo 4: se te ratos fo ram tratados com L - NAME e tadalafila (5mg/kg); Grupo 5 : seis ratos foram tratados com L - NAME, tadala fila e tansulosina. Após trinta dias de tratamento, os animais foram submetidos a estudou rodinâmico. As seguintes variáveis urodinâmicos foram avaliadas. Na fase de enchimento: freqüência de contrações não - miccionais (hiperatividade detrusora), limiar de volume (LV), limiar de pressão (LP) e na fase miccional: pressão de pico (PP), freqüência dos ciclos de micção por minuto (FM), pressão basal (PB) e volume residual...

Recently, it has been observed an association between BPH and ED. It was reported that patients wi th ED treated with inhibitory phosphodiesterase type 5 ( I PDE5) improves erection and LUTS. The pathophysiology of lower urinary tract symptoms (LUTS) is not completely known, so it is necessary that clinical and experimental studies are made to clarify the mechanisms involved in its origin. However, despite the knowledge that there is improvement in LUTS, it is not known whether I PDE5 works during storage, emptying, or both. It is not yet known if the association I PDE5 with alpha blocker is better than its use alone or whether this association is safe. The aim of this study was to evaluate the safety of the combination of tamsulosin with daily tadalafil as well as its effect on lower urinary tract in human and rats by urodynamic study. METHODS : it was an ex perimental study using rats with chronic bladder outlet obstruction induced by L - NAME and a randomized clinical trial, double - blind, placebo - controlled study. In the experimental study, the animals were divided into 05 groups. Group 1: six rats were treate d without medication; Group 2: six rats were treated with L - NAME (60 mg/Kg/dia); Group 3: six rats were treated with L - NAME and t ansulosin (1mg/kg); Group 4: seven rats were treated with L - NAME and tadalafil (5mg/kg); grupo 5: six rats were treated with L - NAME, tadalafil and Tansulosina. After thirty days of oral treatment, the animals underwent urodynamic study. The urodynamic variables were evaluated. In the filling phase: non - void contractions (NVC) , volume threshold (VT), pressure threshold (TP) and in the voiding phase: peak pressure (PP), micturition frequency (FM), basal pressure (PB) and residual volume...

A meta-regression evaluating the effectiveness and prognostic factors of oral phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction / 亚洲男科学杂志(英文版)

The effectiveness of phosphodiesterase type 5 inhibitors (PDE5-Is) for erectile dysfunction (ED) varies considerably among trials, but available studies investigating the factors that affect the effectiveness are few and findings are not consistent. A systematic search was performed in PubMed, Cochrane Library, and EMBASE to identify randomized controlled trials comparing PDE5-Is with placebo for the treatment of ED. The methodological quality of included studies was assessed by the Cochrane Collaborations tool for assessing risk of bias. The associations between prespecified study-level factors and effectiveness were tested by a random effects meta-regression model. This study included 93 trials with 26 139 patients. When all PDE5-Is were grouped together, Caucasian ethnicity was associated with 15.636% (95% confidence interval [CI]: 0.858% to 32.579%) increase in risk ratio (RR) for Global Assessment Questionnaire question-1 (GAQ-1), and 1.473 (95% CI: 0.406 to 2.338) score increase in mean difference (MD) for posttreatment International Index of Erectile Function-Erectile Function domain score (IIEF-EF), compared to Asian ethnicity. A one-score increase in baseline IIEF-EF was associated with -5.635% (95% CI: -9.120% to -2.017%) reduction in RR for GAQ-1, and -0.229 (95% CI: -0.425 to -0.042) score decrease in MD for posttreatment IIEF-EF. In conclusion, PDE5-Is are more effective in Caucasians than Asians, and in patients with more severe ED.

Utilization, Safety, and Related Factors of Illegal Phosphodiesterase Type 5 Inhibitors in South Korean Men

BACKGROUND: Phosphodiesterase Type 5 Inhibitors (PDE5Is), which are prescription drug in South Korea, have been concerned about misuse, overuse and illegal provision of the drugs. This study was performed to investigate utilization and safety of illegal Phosphodiesterase Type 5 Inhibitors (PDE5Is), and related factors among South Korean men. METHODS: A questionnaire survey was conducted from May to July in 2013 among 1,500 nationally representative general males using computer-assisted telephone interview (CATI). The questionnaire included the characteristics of population, the characteristics of PDE5Is use, the experience with the use of illegally obtained PDE5Is, and adverse events after PDE5Is use. RESULTS: Among study population, the 1,015 (67.7%) men answered that they have used the illegally obtained PDE5Is. Younger age, single, lower frequency of PDE5Is use in a lifetime was associated with an increased use of illegally obtained PDE5Is. The men experienced adverse events after PDE5Is use is 528 (35.2%). The most common adverse event was mild to moderate hot flashes. CONCLUSION: We need to enhance awareness about the risk of illegally obtained PDE5Is use, especially in younger men and single. Proactive educations and public relations on safe use of PDE5Is for proper patients are needed.

Recent Advances in the Management of Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening and progressive disease characterized by pulmonary vascular remodeling that leads to increased pulmonary vascular resistance and pulmonary arterial pressure, most often resulting in right-sided heart failure. Originally considered to be a disorder of vasoconstriction and vasodilatation, it has become clear that the predominant characteristic of PAH is abnormal cellular proliferation leading to progressive obliteration of the pulmonary vasculature. Current PAH-specific therapies target one of three major pathways involved in development and progression of PAH: 1) The endothelin pathway targeted by the endothelin receptor antagonists (ERAs); 2) the prostacyclin pathway, targeted by prostacyclin analogs and 3) the nitric oxide (NO) pathway, targeted by the phosphodiesterase type 5 (PDE-5) inhibitors.