Prevalencia y factores asociados al deseo sexual hipoactivo en hombres del Quindío / Prevalence and Factors Associated with Hypoactive Sexual Desire in Quindío Men

Introducción El deseo sexual hipoactivo describe el bajo interés hacia la actividad sexual en general, caracterizando la escasa o nula motivación para tener relaciones eróticas, con disminución o ausencia de pensamientos o fantasías sexuales. Objetivo Evaluar la prevalencia y factores asociados, al deseo sexual hipoactivo en hombres del Quindío, así como estimar las demás disfunciones sexuales. Métodos Estudio observacional. La población estuvo constituida por 171 hombres que asistieron a consulta externa en una clínica universitaria de la ciudad de Armenia, Colombia, en el 2019. Se excluyeron los hombres menores de 18 años, residentes fuera del Quindío, situación psicopatológica o social que dificultara la comprensión del instrumento y los que no consintieron participar en el estudio. Se aplicó como instrumento el "Massachusetts General Hospital-Sexual Functioning Questionnaire (MGH-SFQ)". Se evaluaron las características socio-demográficas, estilos de vida, salud sexual y reproductiva, antecedentes y comportamiento sexual. Se hizo análisis descriptivo. Resultados La edad promedio fue de 41,79 ± 11,46 años (rango 18­81). La prevalencia de disfunciones sexuales en el grupo estudiado fue de 21,63%. La puntuación del MGH-SFQ fue de 14,61 ± 4,23 puntos (variación: 7,26 - 19,26). Se presentaron dificultades con el interés sexual (15,78%), excitación sexual (6,43%), orgasmo (8,77%), erección (21,63%) y satisfacción sexual global (12,28%). La mediana de disfunciones sexuales por hombre fue de 2, que se hizo presente en el 27,48% %. El análisis multivariado (regresión logística) mostró que los factores asociados al deseo sexual hipoactivo fueron testosterona baja (OR: 5,59; IC95% 1,82­18,37), ansiedad / depresión (OR: 5,53; IC95% 1,72­18,43), convivencia en pareja mayor a 10 años (OR: 5,19; IC95%: 2,71­11,71), ansiedad de desempeño (OR: 4,62; IC95% 1,95­10,56), incremento de la edad (OR: 3,42; IC95%: 1,26­9,36), cansancio / estrés (OR: 2,58; IC95%: 1,08­3,28), trastornos del sueño (OR: 1,89; IC95%: 1,35­2,58), conflictos de pareja (OR: 1,53; IC95%: 1,02­2,37) y antecedente de disfunciones sexuales (OR: 1,47; IC95%: 0,99­2,22); mientras que, el uso de juguetes sexuales (OR: 0,78; IC95%: 0,72­0,96; p = 0,021), consumo de vitamina D (2000 UI / diarias) (OR: 0,64; IC95%: 0,42­0,96) o de Inhibidores de fosfodiesterasa-5 (OR: 0,78; IC95%: 0,63­0,93) constituyeron factores protectores. Conclusiones En el presente estudio, el 21,63% de los hombres presentaron disfunciones sexuales. Los trastornos de la erección (21,63%) y el interés sexual (15,78%), fueron los más afectados. La testosterona baja, ansiedad / depresión y convivencia en pareja mayor a 10 años, encabezan los principales factores asociados al deseo sexual hipoactivo. El hacer actividades juntos (OR: 0,44; IC95%: 0,34­0,68), el respeto a ser personas diferentes (OR: 0,53; IC95%: 0,41­0,71), mantener la armonía en la pareja (OR: 0,61; IC95%: 0,47­0,79) y la expresión de sentimientos a la pareja (OR: 0,68; IC95%: 0,46­0,95) constituyen una línea de protección para mejorar las estrategias de prevención de los trastornos sexuales en esa población

Introduction Hypoactive sexual desire describes the low interest in sexual activity in general, characterizing the little or no motivation to have erotic relationships, with a decrease or absence of sexual thoughts or fantasies. Objective To determine the sexual dysfunctions and to evaluate the prevalence and associated factors, to the hypoactive sexual desire in men of Quindío. Methods Observational study. The population consisted of 171 men who attended an outpatient clinic at a university clinic in the city of Armenia, Colombia, in 2019. Men under 18 years of age, residents outside of Quindío, psychopathological or social situation that made understanding difficult, were excluded of the instrument and those who did not consent to participate in the study. The "Massachusetts General Hospital-Sexual Functioning Questionnaire (MGH-SFQ)" was applied as an instrument. Socio-demographic characteristics, lifestyles, sexual and reproductive health, background and sexual behavior were evaluated. Descriptive analysis was done. Results The average age was 41.79 ± 11.46 years (variation: - 81). The prevalence of sexual dysfunctions in the study group was 21.63%. The MGH-SFQ score was 14.61 ± 4.23 points (range between 7.26 - 19.26). There were difficulties with sexual interest (15.78%), sexual arousal (6.43%), orgasm (8.77%), erection (21.63%) and overall sexual satisfaction (12.28%). The median sexual dysfunction per man was 2, which was present in 27.48%%. The multivariate analysis (logistic regression) showed that the factors associated with hypoactive sexual desire were low testosterone (OR: 5.59; 95% CI 1.82­18.37), anxiety / depression (OR: 5.53 ; 95% CI 1.72­18.43), cohabitation in a couple older than 10 years (OR: 5.19; 95% CI: 2.71­11.71), performance anxiety (OR: 4.62; 95% CI 1.95­10.56), increase in age (OR: 3.42; 95% CI: 1.26­9.36), fatigue / stress (OR: 2.58; 95% CI: 1.08­3, 28), sleep disorders (OR: 1.89; 95% CI: 1.35­2.58), couple conflicts (OR: 1.53; 95% CI: 1.02­2.37) and a history of sexual dysfunctions (OR: 1.47; 95% CI: 0.99­2.22); while, the use of sex toys (OR: 0.78; 95% CI: 0.72­0.96; p = 0.021), vitamin D consumption (2000 IU / daily) (OR: 0.64; 95% CI: 0.42­0.96) or of phosphodiesterase-5 inhibitors (OR: 0.78; 95% CI: 0.63­0.93) constituted protective factors. Conclusions In the present study, 21.63% of men had sexual dysfunction. Disorders of erection (21.63%) and sexual interest (15.78%) were the most affected. Low testosterone, anxiety / depression and coexistence in a couple older than 10 years, lead the main factors associated with hypoactive sexual desire. Low testosterone, anxiety / depression and coexistence in couples older than 10 years, are the main factors associated with hypoactive sexual desire. Doing activities together (OR: 0.44, 95% CI: 0.34­0.68), respect for being different people (OR: 0.53, 95% CI: 0.41­0.71), maintaining harmony in the couple (OR: 0.61; 95% CI: 0.47­0.79) and the expression of feelings toward the couple (OR: 0.68; 95% CI: 0.46­0.95) constitute a protection line to improve prevention strategies for sexual disorders in this population.

Do avanafil and zaprinast exert positive effects on bone tissue via the nitric oxide/cyclic guanosine monophosphate/protein kinase-G signaling pathway in rats with ovariectomy-induced osteoporosis?

Phosphodiesterase-5 inhibitors (PDE-5Is) exert positive effects on bone healing and mineralization by activation the nitric oxide/cyclic guanosine monophosphate/protein kinase-G (NO/cGMP/PKG) signaling pathway. In this study, the effects of zaprinast and avanafil, two PDE-5Is, on the NO signaling pathway, estrogen levels, selected bone formation and destruction marker levels, whole-body bone mineral density (WB-BMD), right femur trabecular bone thickness (RF-TBT) and epiphyseal bone width, angiogenesis in the bone-marrow, and selected oxidative stress parameter levels were investigated in rats with ovariectomy-induced osteoporosis. Twenty four adult rats (8 months old) were equally divided into four groups. The first group was the sham operated group. Groups 2, 3 and 4 included ovariectomized rats. At six months after ovariectomy, the 3rd and 4th groups were administered 10 mg/kg zaprinast and avanafil daily as a single dose for 60 days, respectively. Increases in the activity of the NO/cGMP/PKG signalling-pathway, C-terminal collagen peptide levels, angiogenesis in the bone marrow, RF-TBT, epiphyseal bone width and WB-BMD were observed compared to the ovariectomized positive control group (OVX), while the pyridinoline and deoxypyridinoline levels were decreased in the OVX+zaprinast and OVX+avanafil groups (p<0.05). The malondialdehyde, ubiquinone10/ubiquinol10 and 8-hydroxy-2-deoxyguanosine/106deoxyguanosine levels were also increased in the ovariectomized groups compared to the sham group (p<0.05). Based on these results, the levels of bone atrophy and some markers of oxidative stress were increased due to acute estrogen deficiency induced by ovariectomy, but zaprinast and avanafil administration significantly prevented these changes

Mecanismo de Frank Starling: una visión aplicada en la erección del pene / Frank-Starling Mechanism: A Vision Applied To Penile Erection

El mecanismo de Frank-Starling es un concepto básico de la fisiología cardíaca y su aprendizaje. Constituye la base fundamental para el entendimiento del funcionamiento del corazón y patologías prevalentes y con alta morbimortalidad como lo es la insuficiencia cardíaca. Por lo cual, su relación con un proceso más interactivo como la erección del pene, podría asegurar un aprendizaje perdurable y práctico. La relación se fundamentó en el reemplazo del eje X de la curva por precarga en el caso del corazón y estimulación en el caso del pene, para así lograr una relación incluso con la disfunción eréctil, que sería el equivalente a la insuficiencia cardíaca. De esa manera, se encontró que a mayor estimulación hay mayor erección y a mayor precarga hay mayor eyección ventricular, teniendo ambas curvas una meseta. Asímismo, farmacológicamente, se encontró relación con el uso de estimulación ß-adrenérgica y de inhibidores selectivos de la fosfodiesterasa tipo 5 como el sildenafil, los cuales desplazan la curva hacia arriba y a la izquierda.

The Frank-Starling mechanism is a basic concept of cardiac physiology and the fundamental basis for understanding the cardiac performance and prevalent disorders at risk of high morbidity and mortality, such as heart failure. Therefore, its relation with an interactive process like penile erection may enable deeper insight into cardiac physiology. The X-axis of Frank-Starling's curve was changed from ventricular end-diastolic volume to stimulation, to achieve a relation that includes erectile dysfunction, which is the equivalent of heart failure. A direct relationship was found between stimulation and erection, as well as end-diastolic volume and ventricular ejection with a plateau in both curves. Likewise, pharmacologically, a relation was identified with the use of ß-adrenergic and selective inhibitor of phosphodiesterase (PDE) type 5 like sildenafil, which shift leftward and upward the Frank-Starling curve

Acute Hemodynamic Changes after Single Administration of Udenafil in Pulmonary Arterial Hypertension: a Phase IIa Study

BACKGROUND AND OBJECTIVES: Udenafil, a new phosphodiesterase-5 inhibitor (PDE5i), has been used to treat erectile dysfunction. Given the proven benefit of PDE5i in pulmonary arterial hypertension (PAH), we evaluated serial hemodynamic changes after single udenafil administration to determine the appropriate therapeutic dose. METHODS: Eighteen patients were randomly allocated into one of 3 groups: placebo, udenafil 50 mg (U50), and udenafil 100 mg (U100). Diagnosis for inclusion was idiopathic PAH or PAH associated with connective tissue disease. Patients with any contraindication to PDE5i, and/or PDE5i treatment in the past 1 month were excluded. Continuous hemodynamic monitoring was performed by placing a Swan-Ganz catheter. Information on cardiac index (CI), mean pulmonary arterial pressure (mPAP), mean systemic arterial pressure (mSAP), pulmonary arterial wedge pressure (PAWP), and pulmonary vascular resistance index (PVRI) was obtained for 4 hours after drug administration. RESULTS: The mPAP significantly decreased in both the U50 and U100 (−11 mmHg and −8 mmHg from baseline, respectively, p < 0.1). The mSAP also decreased in both U50 and U100; however, the decrease was greater in the U100 (Δ=−8.5 mmHg and Δ=−14.0 mmHg). CI increased in the U50, but decreased in the U100. Although PVRI decreased in both, statistical significance was only achieved in the U50 compared to placebo. PAWP was stable during monitoring. U50 had at least 4 hour-effect after administration. Only 2 patients with U100 experienced mild adverse events. CONCLUSIONS: This is the first demonstration of the acute hemodynamic changes induced by udenafil. U50 is considered an optimal dose for treating PAH with more than 4-hour treatment effect. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01553721.

Misuse of testosterone replacement therapy in men in infertile couples and its influence on infertility treatment / 대한생식의학회지

OBJECTIVE: We investigated the clinical characteristics of men with testosterone replacement therapy (TRT)-induced hypogonadism and its effect on assisted reproductive technology (ART) in infertile couples.METHODS: This study examined the records of 20 consecutive male patients diagnosed with azoospermia or severe oligozoospermia (<5×10⁶/mL) who visited a single infertility center from January 2008 to July 2018. All patients were treated at a primary clinic for erectile dysfunction or androgen deficiency symptoms combined with low serum testosterone. All men received a phosphodiesterase 5 inhibitor and TRT with testosterone undecanoate (Nebido®) or testosterone enanthate (Jenasteron®). Patients older than 50 years or with a chronic medical disease such as diabetes were excluded.RESULTS: The mean age of patients was 37 years and the mean duration of infertility was 16.3±11.6 months. At the initial presentation, eight patients had azoospermia, nine had cryptozoospermia, and three had severe oligozoospermia. Serum follicle-stimulating hormone levels were below 1.0 mIU/mL in most patients. Three ongoing ART programs with female factor infertility were cancelled due to male spermatogenic dysfunction; two of these men had normal semen parameters in the previous cycle. After withholding TRT, serum hormone levels and sperm concentrations returned to normal range after a median duration of 8 months.CONCLUSION: TRT with high-dose testosterone can cause spermatogenic dysfunction due to suppression of the hypothalamic-pituitary-testicular axis, with adverse effects on infertility treatment programs. TRT is therefore contraindicated for infertile couples attempting to conceive, and the patient's desire for fertility must be considered before initiation of TRT in a hypogonadal man.

A Case of Sexual Enhancer Induced Fixed Drug Eruption / 대한피부과학회지

Fixed drug eruption is a commonly reported mucocutaneous drug eruption. A 61-year-old male presented to our clinic with a complaint of an itchy round erythematous patch on the left hand dorsum with myalgia. On taking medical history, the patient correlated the episode with the intake of an oral sexual enhancer that he had obtained over the counter. We found the medicine contained tadalafil and sildenafil in combination with herbal ingredients. A short course of oral corticosteroid therapy resulted in the complete resolution of the lesion leaving residual hyperpigmentation of the skin involved. Various sexual enhancers with fancy names and attractive packaging are available without requiring a doctor's prescription. Most contain phosphodiesterase-5 inhibitors in various concentrations, often with herbal additions. These drugs are used erratically by the lay public, and often produce side effects. Herein, we report a case of fixed drug rash related to a sexual enhancer, which we believe to be the first report in Korea.

Udenafil, a Phosphodiesterase 5 Inhibitor, Reduces Body Weight in High-Fat-Fed Mice

PURPOSE: High-fat (HF) feeding induces hypothalamic leptin resistance via the activation of toll-like receptor 4 (TLR4). TLR4 deficiency confers resistance to diet-induced obesity. Udenafil, an anti-impotence drug, inhibits TLR4 in airway epithelial cells in vitro. In this study, we evaluated whether udenafil suppressed the hypothalamic expression of TLR4 and reduced body weight. MATERIALS AND METHODS: The hypothalamic expression of TLR4, phosphodiesterase 5 (PDE5), nuclear factor-κB (NF-κB), and myeloid differentiation primary response gene 88 (Myd88) was analyzed by real-time polymerase chain reaction after treating mice for 2 days with udenafil (0, 12, 120, or 600 µg/d). Furthermore, the hypothalamic expression of TLR4, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY) was analyzed after 9 days' treatment with udenafil and/or leptin. We also measured body weight and food intake following 9 days of udenafil and/or leptin treatment in control- and HF-fed mice. RESULTS: Udenafil suppressed hypothalamic TLR4 mRNA expression dose-dependently. The changes were associated with decreased PDE5, NF-κB, and Myd88 expression. Udenafil treatment for 9 days reduced body weight and caloric intake in HF-fed mice. This may have been associated with the suppression of NPY expression that was elevated by HF feeding. POMC expression was not affected by udenafil. However, udenafil did not augment the effects of leptin on the reduction of body weight and caloric intake in HF-fed mice. CONCLUSIONS: These results suggested that udenafil reduced body weight by suppressing hypothalamic TLR4 mRNA expression in HF-fed mice and the combination effect of udenafil and leptin was additive rather than synergistic.

Daily use of phosphodiesterase type 5 inhibitors as prevention for recurrent priapism / Prevenção do priapismo recorrente com a utilização diária de inibidores da fosfodiesterase tipo 5

Summary Objective: The pathogenesis of recurrent priapism is currently being investigated based on the regulation of the phosphodiesterase 5 (PDE5) enzyme. We explored the daily use of PDE5 inhibitors to treat and prevent priapism recurrences. Method: We administered PDE5 inhibitors using a long-term therapeutic regimen in seven men with recurrent priapism, with a mean age of 29.2 years (range 21 to 35 years). Six men (85.7%) had idiopathic priapism recurrences and one man (24.3%) had sickle cell disease-associated priapism recurrences. Tadalafil 5 mg was administered daily. The mean follow-up was 6.6 months (range 3 to 12 months). Results: Daily long-term oral PDE5 inhibitor therapy alleviated priapism recurrences in all patients. Five (71.4%) had no episodes of priapism and two (28.6%) referred decrease in their episodes of priapism. All patients referred improvement in erectile function. Conclusion: These findings suggest the hypothesis that PDE5 dysregulation exerts a pathogenic role for both sickle cell disease-associated priapism and for idiopathic priapism, and that it offers a molecular target for the therapeutic management of priapism. These preliminary observations suggest that continuous long-term oral PDE5 inhibitor therapy may treat and prevent recurrent priapism.

Resumo Objetivo: Uma das teorias propostas para explicar a etiologia do priapismo recorrente está baseada no mecanismo de regulação da fosfodiesterase tipo 5. Estudamos o uso diário dos inibidores de fosfodiesterase tipo 5 no tratamento e na prevenção do priapismo recorrente. Método: Sete homens com diagnóstico de priapismo recorrente, com idade média de 29,5 anos (21 a 35 anos), utilizaram inibidor de fosfodiesterase tipo 5 em dose diária (tadalafila 5 mg/dia) por período prolongado. Seis homens (85,7%) apresentavam priapismo recorrente de etiologia idiopática, e um homem (24,3%), de etiologia associada à anemia falciforme. O seguimento médio foi de 6,6 meses (3 a 12 meses). Resultados: Todos os pacientes se beneficiaram com a utilização de inibidores de fosfodiesterase tipo 5. Cinco (71,4%) não apresentaram nenhum episódio de priapismo e dois (28,6%) relataram diminuição dos episódios. Todos os pacientes relataram melhora da função erétil. Conclusão: Estes achados sugerem que a hipótese do mecanismo de regulação da fosfodiesterase tipo 5 exerce papel importante na patogenia do priapismo recorrente. O uso contínuo e diário de inibidores da fosfodiesterase tipo 5 pode ser uma opção no tratamento do priapismo recorrente.

Recreational Use of Phosphodiesterase 5 Inhibitors and Its Associated Factors among Undergraduate Male Students in an Ethiopian University: A Cross-Sectional Study

PURPOSE: To assess the prevalence of phosphodiesterase 5 (PDE5) inhibitor use and associated factors among University of Gondar undergraduate students. MATERIALS AND METHODS: An institution-based, cross-sectional study, using a survey questionnaire, was conducted from October to December 2015 to assess PDE5 inhibitor use and associated factors among male students at the University of Gondar. A Self-Esteem and Relationship questionnaire (14 items), an International Index of Erectile Function questionnaire (15 items) and a questionnaire on PDE5 inhibitor use (14 items) were included in the survey. RESULTS: Across all respondents (age, 21.9±1.88 years), more than half (55.7%, n=233) had heard about PDE5 inhibitors, but only 23 men (5.5%) reported trying a PDE5 inhibitor drug at least once. Older students were more likely to use PDE5 inhibitors compared to younger students (adjusted odds ratio [AOR], 1.40; 95% confidence interval [CI], 1.109~1.768). Those students who were smokers were 5.15 times more likely to use PDE5 inhibitors as compared to their non-smoking counterparts (AOR, 5.15; 95% CI, 2.096~12.687). In addition, multivariate logistic regression showed that being in a relationship, alcohol use, greater number of cigarettes smoked per day, and more sexual partners were significantly associated with PDE5 inhibitor use. CONCLUSIONS: The prevalence of PDE5 inhibitor use among undergraduate students was 5.5%. Cigarette smoking and other substance use, older age, and greater number of sexual partners were significantly associated factors for PDE5 inhibitor use. These findings suggest that restricting access to PDE5 inhibitor drugs is essential to curtailing misuse among university students.

Two Distinct Types of Hypercontractile Esophagus: Classic and Spastic Jackhammer

Hypercontractile esophagus (nicknamed jackhammer esophagus) is a recently defined disease within the esophageal motility disorders classification. Responses to treatments for jackhammer esophagus have been inconsistent in previous trials, possibly due to its heterogeneous manifestation. Thus, we reviewed 10 patients diagnosed with jackhammer esophagus and compared their clinical and manometric features at baseline. Additionally, manometric and symptomatic responses after treatment with known smooth muscle relaxants, including anticholinergic drugs (cimetropium bromide and scopolamine butylbromide) and a phosphodiesterase-5 inhibitor (sildenafil) were compared. We observed two distinct subgroups in the findings: one with hypercontractility and normal distal latencies (“classic jackhammer esophagus,” n=7) and the other with hypercontractility and short distal latencies (“spastic jackhammer esophagus,” n=3). The two types also differed in their responses to medications in that symptoms improved upon treatment with an anticholinergic agent in classic jackhammer esophagus patients, while spastic jackhammer esophagus was unresponsive to both the anticholinergic drugs and the phosphodiesterase-5 inhibitor. In conclusion, hypercontractile esophagus may be a heterogeneous disease with different underlying pathophysiologies. We introduced two novel terms, “classic jackhammer esophagus” and “spastic jackhammer esophagus,” to distinguish the two types.

Evolution of Phosphodiesterase-5 Inhibitors

No abstract available.

A Meta-Analysis of Long- Versus Short-Acting Phosphodiesterase 5 Inhibitors: Comparing Combination Use With alpha-Blockers and alpha-Blocker Monotherapy for Lower Urinary Tract Symptoms and Erectile Dysfunction / 대한배뇨장애요실금학회지

PURPOSE: Combination therapy with an alpha-1-adrenergic blocker and phosphodiesterase type 5 inhibitors (PDE5Is) has shown improvements in lower urinary tract symptoms (LUTS) with negligible side effects. Nonetheless, decisive advantages in symptom improvement were insufficient, and there were no clinical differences between long- or short-acting PDE5Is in combination with combination medication. METHODS: To review the studies on alpha-1-adrenergic blocker monotherapy and combination therapy with long vs. short-acting PDE5Is in their use in LUTS and erectile dysfunction (ED). A search of the MEDLINE, Embase, Cochrane Library, and KoreaMed databases was conducted from 2000 to 2014 using combinations of the relevant terms. Among the 323 relevant references discovered, 10 were selected for meta-analysis. The data showed that 616 men received combination therapy (PDE5Is with alpha-1-adrenergic blockers) or alpha-1-adrenergic blocker monotherapy. RESULTS: Meta-analysis of the combination therapy showed it was more effective than alpha-blockers in improving symptoms, with a mean International Prostrate Symptom Score change difference of -1.93 while those of the long- vs. short-acting PDE5I were -2.12 vs. -1.70. Compared to maximum flow rate (Qmax) value with monotherapy, the Qmax increased more with the combination therapy (mean difference of 0.71) while change values were 0.14 and 1.13 for the long- and short-acting PDE5Is, respectively. Residual urine decreased more with the combination therapy than it did with alpha-1-adrenergic blocker monotherapy with a mean difference of -7.09 while the mean residual urine change values for long- vs. short-acting PDE5Is were -18.83 vs. -5.93. The International Index of Erectile Function value increased by 3.99, 2.85, and 4.85 following combination therapy, and therapy with long- and short-acting PDE5Is. CONCLUSIONS: Our meta-analysis suggests that PDE5Is can signicantly improve LUTS in men with benign prostatic hyperplasia/ED. Furthermore, combination PDE5I and alpha-1-adrenergic blocker could be a more effective treatment than alpha-1-adrenergic blocker monotherapy, and the differences between long and short-acting agents were minimal.

Adenoviral short hairpin RNA targeting phosphodiesterase 5 attenuates cardiac remodeling and cardiac dysfunction following myocardial infarction in mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the impact of PDE5shRNA on cardiac remodeling and heart function following myocardial infarction in mice.</p><p><b>METHODS</b>Myocardial infarction (MI) was induced in mice by left coronary artery ligation. Mice were randomly assigned to sham group (n = 6), PDE5shRNA group (n = 12), common adenovirus group (n = 15) and DMEM group (n = 8). Four weeks post-MI, the survival rate was evaluated. Cardiac function was examined by echocardiography. HE staining and Masson staining were used to evaluate the myocardial infarction size and fibrosis. The number of blood vessels was evaluated by immunohistochemistry, PDE5 protein expression in the left ventricular was detected using Western blot, level of cGMP or PKG activity in the left ventricle was evaluated with ELISA.</p><p><b>RESULTS</b>Four weeks post-MI, all mice survived in the sham group, 3(37%) mice died in the DMEM group, 1 (8%) died in the PDE5shRNA group and 5 died in the common adenovirus group (33%). Infarct size was significantly reduced in PDE5shRNA group compared with the common adenovirus group and DMEM group [(25.4 ± 2.9)% vs. (42.0 ± 3.2)% and (43.4 ± 2.6) %, P < 0.05]. Cardiac function was significantly improved in PDE5shRNA group compared to common adenovirus group and DMEM group[LVFS: (21.1 ± 3.7)% vs. (14.2 ± 2.9)% and (14.22 ± 2.91)%, all P < 0.05; LVEF: (48.2 ± 7.1)% vs. (34.6 ± 6.2)% and (38.1 ± 2.8)%, all P < 0.05; LVESD: (3.87 ± 0.45) mm vs.(4.91 ± 0.62) mm and (4.63 ± 0.37) mm, all P < 0.05]. The blood vessel density was also higher in PDE5shRNA group compared with common adenovirus group (infarct area:14.3 ± 2.0 vs. 6.6 ± 1.2, P < 0.05; periinfarct area: 23.6 ± 2.1 vs. 13.7 ± 2.4, P < 0.05). Compared with common adenovirus group, level of PDE5 was significantly downregulated and level of cGMP or PKG was significantly upregulated in PDE5shRNA group (all P < 0.05).</p><p><b>CONCLUSIONS</b>Present study suggests PDE5shRNA improves cardiac function and attenuates cardiac remodeling through reducing infarction size and cardiac fibrosis and these beneficial effects are possibly mediated by activating cGMP/PKG signaling pathway.</p>

Urologists' Perceptions and Practice Patterns in Peyronie's Disease: A Korean Nationwide Survey Including Patient Satisfaction

PURPOSE: A nationwide survey was conducted of Korean urologists to illustrate physicians' perceptions and real practical patterns regarding Peyronie disease (PD). MATERIALS AND METHODS: A specially designed questionnaire exploring practice characteristics and attitudes regarding PD, as well as patient satisfaction with each treatment modality, was e-mailed to 2,421 randomly selected urologists. RESULTS: Responses were received from 385 practicing urologists (15.9%) with a median time after certification as an urologist of 12 years. Regarding the natural course, 87% of respondents believed that PD is a progressive disease, and 82% replied that spontaneous healing in PD occurred in fewer than 20% of patients. Regarding diagnosis of PD, the methods used were, in order, history taking with physical examination (98%), International Index of Erectile Function questionnaires (40%), intracavernous injection and stimulation (35%), and duplex sonography (28%). Vitamin E was most preferred as an initial medical management (80.2%), followed by phosphodiesterase-5 inhibitors (27.4%) and Potaba (aminobenzoate potassium, 20.1%). For urologists who administered intralesional injection, the injected agent was, in order, corticosteroid (72.2%), verapamil (45.1%), and interferon (3.2%). The most frequently performed surgical procedure was plication (84.1%), followed by excision and graft (42.9%) and penile prosthesis implantation (14.2%). Among the most popular treatments in each modality, the urologists' perceptions regarding the suitability of treatment and patient satisfaction were significantly different, favoring plication surgery. CONCLUSIONS: The practice pattern of urologists depicted in this survey is in line with currently available Western guidelines, which indicates the need for development of further local guidelines based on solid clinical data.

Comparative Efficacy of Tamsulosin Versus Tamsulosin With Tadalafil in Combination With Prednisolone for the Medical Expulsive Therapy of Lower Ureteric Stones: A Randomized Trial

PURPOSE: To compare the safety and efficacy of tamsulosin and tamsulosin with the phosphodiesterase-5 inhibitor tadalafil in combination with prednisolone as medical expulsive therapies for lower ureteric stones. MATERIALS AND METHODS: Between July 2011 and December 2012, 62 adult patients presenting with distal ureteric stones sized 5 to 10 mm were randomized equally to treatment with tamsulosin (group A) or tamsulosin with tadalafil (group B). Therapy was given for a maximum of 6 weeks. In addition, patients in groups A and B were given 5-mg prednisolone once daily (maximum 1 week). The stone expulsion rate, time to stone expulsion, analgesic use, number of hospital visits for pain, follow-up and endoscopic treatment, and adverse effects of the drugs were noted. Statistical analyses were done by using Student t-test and chi-square test. RESULTS: There was a higher expulsion rate (83.9% in group B and 74.2% in group A) and a lower time to expulsion in both treatment groups than in historical controls used in earlier studies. However, these results were not statistically significant (p=0.349, p=0.074, respectively). Statistically significant differences were noted in hospitalization for colic and analgesic requirement, which were less in group B than in group A. There were no serious adverse events. Another important finding was improvement in erectile function in group B. CONCLUSIONS: Medical expulsive therapy for distal ureteric stones using tamsulosin and tadalafil with prednisolone is safe and efficacious. Also, the prescription of tadalafil in cases of erectile dysfunction with the development of lower ureteric stones may provide additional advantages.

A Case of Patient with Eisenmenger Syndrome Admitted to Intensive Care Unit Due to Septic Shock Complicated with Newlydiagnosed Down Syndrome and Moyamoya Disease / 대한구급학회지

Eisenmenger syndrome is a severe form of pulmonary arterial hypertension related to congenital cardiac defects. Many patients die at a young age from such complications. The treatment of primary pulmonary hypertension is being applied to Eisenmenger syndrome such as endothelin receptor antagonists, phosphodiesterase-5 blockers, and prostacyclin. We experienced a case of 29-year female with ventricular septal defect-related Eisenmenger syndrome complicated with Down syndrome and Moyamoya disease, who was admitted to intensive care unit due to enteritis-associated septic shock. After the combination treatment with iloprost and sildenafil within the intensive care unit, the patient was able to wean mechanical ventilation without further applications of invasive rescue therapy such as extracorporeal membrane oxygenator. She was later discharged with bosentan. She maintained bosentan therapy for 34 months continuously without aggravations of symptom but eventually died with intracranial hemorrhage, a complication of Moyamoya disease. To our knowledge, this is the first case report of Eisenmenger syndrome accompanied by mosaic Down syndrome and Moyamoya disease.

Calcineurin/NFAT signaling pathway mediates endothelin-1-induced pulmonary artery smooth muscle cell proliferation by regulating phosphodiesterase-5 / 南方医科大学学报

<p><b>OBJECTIVE</b>To examine whether calcineurin/NFAT signaling pathway mediates endothelin-1 (ET-1)-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) by regulating phosphodiesterase-5 (PDE5) and the effect of the selective calcineurin inhibitor cyclosporine A and PDE5 inhibitor sildenafil on ET-1-induced PASMC proliferation.</p><p><b>METHODS</b>PASMCs were treated with ET-1 to stimulate their proliferation with or without prior treatment of the cells with CsA or sildenafil. Calcineurin activity in the cells was measured using a calcineurin activity assay kit, PDE5 expression examined using immunoblotting, and cGMP level detected using a cGMP direct immunoassay kit. PASMC proliferation following the treatments was determined using [(3)H]thymidine incorporation assay.</p><p><b>RESULTS</b>ET-1 caused a 2.05-fold increase in the cellular calcineurin activity, a 1.80-fold increase in PDE5 expression, and a 3.20-fold increase in the DNA synthesis rate, and reduced the cGMP level by 67%. Pretreatment of the cells with Cyclosporine blocked the effects of ET-1, and PDE5 inhibition by sildenafil pretreatment also abolished ET-1-induced reduction of cGMP level in the cells. Both Cyclosporine and sildenafil suppressed ET-1-stimulated PASMC proliferation.</p><p><b>CONCLUSION</b>Activation of calcineurin/NFAT signaling pathway mediates ET-1-induced PASMC proliferation by stimulating PDE5 expression, which further degrades cGMP. Both Cyclosporine and sildenafil can suppress ET-1-stimulated PASMC proliferation in vitro.</p>

Effects of Mirodenafil, a Phosphodiesterase-5 Inhibitor, on Female Rat Bladder in a Partial Bladder Outlet Obstruction Model: Physiological and Immunohistochemical Aspects

PURPOSE: We investigated the effects of mirodenafil, a phosphodiesterase-5 inhibitor developed in South Korea, on the female rat bladder in a partial bladder outlet obstruction (BOO) model. MATERIALS AND METHODS: Thirty-six female Sprague-Dawley rats were divided into four groups: the control group, BOO without medication group, BOO with mirodenafil 1 mg/kg group, and BOO with mirodenafil 4 mg/kg group. Mirodenafil was administered orally for 2 weeks after the induction of BOO. Two weeks after BOO, the rats in each group underwent cystometry under urethane anesthesia. After cystometry, the bladder was excised to perform immunohistochemical staining for connexin 43. RESULTS: The three BOO groups showed significant increases in mean bladder weight compared with the control group. Baseline pressure, threshold pressure, and maximum contraction pressure were not significantly different between the four groups. Although the contraction interval was decreased in all BOO groups compared with the control group, it was prolonged in the two groups treated with mirodenafil compared with the untreated BOO group. In the immunohistochemical examination, connexin 43 staining intensity in the lamina propria increased in the three BOO groups compared with the control group. The two groups treated with mirodenafil, however, showed decreased connexin 43 staining compared with the untreated BOO group. CONCLUSIONS: Mirodenafil may increase the contraction intervals of female rat bladders in a partial BOO model. Decreasing bladder overactivity by mirodenafil may be related to intracellular communication mechanisms involving connexin 43.