RESUMEN
Many studies have demonstrated the mechanisms of progression to castration-resistant prostate cancer (CRPC) and novel strategies for its treatment. Despite these advances, the molecular mechanisms underlying the progression to CRPC remain unclear, and currently, no effective treatments for CRPC are available. Here, we characterized the key genes involved in CRPC progression to gain insight into potential therapeutic targets. Bicalutamide-resistant prostate cancer cells derived from LNCaP were generated and named Bical R. RNA sequencing was used to identify differentially expressed genes (DEGs) between LNCaP and Bical R. In total, 631 DEGs (302 upregulated genes and 329 downregulated genes) were identified. The Cytohubba plug-in in Cytoscape was used to identify seven hub genes (ASNS, AGT, ATF3, ATF4, DDIT3, EFNA5, and VEGFA) associated with CRPC progression. Among these hub genes, ASNS and DDIT3 were markedly upregulated in CRPC cell lines and CRPC patient samples. The patients with high expression of ASNS and DDIT3 showed worse disease-free survival in patients with The Cancer Genome Atlas (TCGA)-prostate adenocarcinoma (PRAD) datasets. Our study revealed a potential association between ASNS and DDIT3 and the progression to CRPC. These results may contribute to the development of potential therapeutic targets and mechanisms underlying CRPC progression, aiming to improve clinical efficacy in CRPC treatment.
Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Línea Celular Tumoral , Biología Computacional , Neoplasias de la Próstata Resistentes a la Castración/patología , Factor de Transcripción CHOP , Resultado del TratamientoRESUMEN
BACKGROUND: Extracellular vesicles (EVs) contain thousands of proteins and nucleic acids, playing an important role in cell-cell communications. Sertoli cells have been essential in the testis as a "nurse cell". However, EVs derived from human Sertoli cells (HSerCs) have not been well investigated. METHODS: EVs were isolated from HSerCs via ultracentrifugation and characterized by transmission electron microscopy, tunable resistive pulse sensing, and Western blotting. The cargo carried by HSerCs-EVs was measured via liquid chromatography-mass spectrometry and GeneChip miRNA Arrays. Bioinformatic analysis was performed to reveal potential functions of HSerCs-EVs. RESULTS: A total of 860 proteins with no less than 2 unique peptides and 88 microRNAs with high signal values were identified in HSerCs-EVs. Biological processes related to molecular binding, enzyme activity, and regulation of cell cycle were significantly enriched. Specifically, many proteins in HSerCs-EVs were associated with spermatogenesis and regulation of immune system, including Septins, Large proline-rich protein BAG6, Clusterin, and Galectin-1. Moreover, abundant microRNAs within HSerCs-EVs (miR-638, miR-149-3p, miR-1246, etc.) had a possible impact on male reproductive disorders such as asthenozoospermia and oligozoospermia. CONCLUSIONS: Our study has shown that HSerCs-EVs contain diverse components such as proteins and microRNAs. Further research is required to evaluate HSerCs-EVs in spermatogenesis, which are underutilized but highly potent resources with particular promise for male infertility.
Asunto(s)
Vesículas Extracelulares , MicroARNs , Cromatografía Liquida , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Humanos , Masculino , MicroARNs/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas/metabolismo , Proteómica , Células de Sertoli/metabolismoRESUMEN
BACKGROUND: Primary plantar hyperhidrosis (PPH) is an idiopathic disease, characterized by excessive sweating of the feet. It leads to significant disturbance in private and professional daily lifestyle, due to excessive sweating. The aim of this study is to present the safety, efficacy and procedures of retroperitoneoscopic lumbar sympathectomy (RLS) for treatment of PPH. METHODS: RLS was performed 60 times in 30 patients (18 men, 12 women) with PPH in our institution from May 2019 to October 2020. All procedures were carried out by laparoscopy with retroperitoneal approach. Clinical data including patient demographics and perioperative, postoperative outcomes were evaluated. Recurrence of symptoms, and any adverse effects of surgery were evaluated after 7 to 30 days in outpatient clinic, and thereafter every 6 months. RESULTS: Mean age of patients was 33.6 (± standard deviation 10.8) years. Fourteen and fifteen patients were previously treated with medical therapy or endoscopic thoracic sympathectomy (ETS) respectively. Mean preoperative quality of life (QoL) score of patients was 91.8 (VERY BAD), but postoperative 12 months (QoL) score decreased to 29.1 (MUCH BETTER). There was no serious postoperative complication. During the mean 22 months of follow-up period, no compensatory sweating was observed. CONCLUSIONS: RLS can be a safe and effective surgical treatment for severe PPH, especially for the patients with persistent plantar sweating even after conservative management and ETS. RLS also could be offered to surgeons who are familiar with retroperitoneal space anatomy as feasible surgical treatment for PPH.
Asunto(s)
Hiperhidrosis , Laparoscopía , Niño , Femenino , Humanos , Hiperhidrosis/cirugía , Masculino , Satisfacción del Paciente , Calidad de Vida , Sudoración , Simpatectomía , Resultado del TratamientoRESUMEN
INTRODUCTION: There are only a few studies on the clinical utility of filler injections for penile augmentation (PA) in patients with small penis syndrome (SPS), which is a type of anxiety or body dysmorphic disorder, not a true micropenis. AIM: To compare the clinical outcomes of hyaluronic acid (HA) with polylactic acid (PLA) filler injection for temporary PA in patients with SPS. METHODS: Our prospective, patient/evaluator-blind, comparative, randomized, non-inferiority trial consisted of a single filler injection and a 24-week post-injection period. Seventy-four men with SPS were included between November 2017 and February 2018. Patients were divided into those injected with HA (n = 39) and those injected with PLA filler (n = 35). MAIN OUTCOME MEASURE: The psychological effects of PA, based on the Beliefs about Penis Size Scale, penile girth, and satisfaction, were assessed at baseline and at 4, 12, and 24 weeks post-injection. RESULTS: At 24 weeks, the mean penile girth increases were 2.1 ± 1.0 cm (P < .001) in the HA group and 1.6 ± 0.9 cm (P < .001) in the PLA group, with a mean difference of 0.5 ± 0.2 cm between groups (P = .031). In both groups, satisfaction levels significantly increased at 24 weeks, with 1.8 ± 1.7 and 1.6 ± 1.4 mean increases in the visual analog scale for penile appearance satisfaction in the HA and PLA groups, respectively (each P < .001), and 1.0 ± 1.1 and 0.7 ± 1.2 mean increases in the visual analog scale for sexual life satisfaction in the HA and PLA groups, respectively (each P < .001), with no significant differences between groups (P = .950 and P = .287). The mean Beliefs about Penis Size Scale scores significantly decreased at 24 weeks, with 7.8 ± 8.3 and 5.3 ± 7.2 mean decreases in the HA and PLA groups, respectively (each P < .001), and no significant difference between the groups (P = .920). There were no serious adverse events, but filler injection-related adverse events in the HA and the PLA groups were reported in 2 cases (5.13%) and 5 cases (14.29%), respectively (P = .245). CLINICAL IMPLICATIONS: Our study provides an overview of clinical course after HA and PLA filler injections for PA and suggests that filler injections can be considered an alternative approach in patients with SPS. STRENGTHS & LIMITATIONS: Our study is the first to assess the psychological symptoms in patients with SPS who received the filler injection for PA; however, the follow-up duration was insufficient to prove the long-term outcomes of fillers. CONCLUSION: Without serious adverse events, HA and PLA filler injections for PA significantly resulted in not only an augmentative effect but also improvement of psychological distress, and the clinical utility was comparable between the fillers. Yang DY, Jeong HC, Ahn ST, et al. A Comparison Between Hyaluronic Acid and Polylactic Acid Filler Injections for Temporary Penile Augmentation in Patients with Small Penis Syndrome: A Multicenter, Patient/Evaluator-Blind, Comparative, Randomized Trial. J Sex Med 2020;17:133-141.
Asunto(s)
Enfermedades de los Genitales Masculinos/tratamiento farmacológico , Ácido Hialurónico/administración & dosificación , Pene/anomalías , Poliésteres/administración & dosificación , Adulto , Método Doble Ciego , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Pene/efectos de los fármacos , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Objectives: We investigate the effects of Ojayeonjonghwan (KH-204) in men with late-onset hypogonadism (LOH) symptoms.Material and methods: Initial PSA, testosterone, lipid profile and questionnaires about LOH-related symptoms were checked. After 8 weeks of the treatment (control or KH-204), questionnaires and serological tests were repeated to evaluate the efficacy of the agent. The changes of variables in each group and the difference between two groups were compared.Results: A total of 78 men were enrolled, and randomly assigned to the control group (n = 39) or KH-204 group (n = 39). Baseline characteristics of both group are comparable. AMS total score of control and KH-204 group were both improved at 8 weeks (p = .010, <.001), and there was a statistically significant difference between the two groups (favorable in KH-204 group, p = .006). At 8 weeks, total IIEF score of control and KH-204 group were both improved, and there was no statistically significant difference in the degree of improvement between the two groups (p = .303). There was no statistically significant difference of laboratory findings, in intra-group changes and inter-group comparisons.Conclusions: KH-204 was found to be effective in all LOH symptoms without changing of laboratory results. KH-204 may be safely used for treatment of male with LOH-related symptoms.
Asunto(s)
Terapia de Reemplazo de Hormonas/métodos , Hipogonadismo/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Anciano , Envejecimiento/fisiología , Método Doble Ciego , Humanos , Hipogonadismo/sangre , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Testosterona/sangreRESUMEN
Purpose: To evaluate the pharmacological effects of goji berry (Lycium chinense P. Mill) in an animal model of late-onset hypogonadism (LOH).Materials and methods: Thirty 18-month-old male Sprague-Dawley (SD) rats were used as the LOH aged rat model. Rats were divided into five groups: a control group (n = 6), low concentration goji berry extract group (150 mg/kg/day) (n = 6), high concentration goji berry extract group (300 mg/kg/day) (n = 6), low concentration goji berry complex extract group (150 mg/kg/day) (n = 6), and high goji berry complex concentration extract group (300 mg/kg/day) (n = 6). After six weeks of treatment, sperm counts and motility, serum testosterone level, androgen receptor (AR) expression, oxidative stress marker, and apoptotic factors were examined.Results: Goji berry extracts increased testosterone level to 2.07 ± 0.06 pmol/L in the goji berry 150 mg/kg group, 2.39 ± 0.08 pmol/L in the goji berry 300 mg/kg group, 2.97 ± 0.03 pmol/L in the goji berry complex 150 mg/kg group, and 3.34 ± 0.04 pmol/L in the goji berry complex 300 mg/kg group compared to 1.86 ± 0.03 pmol/L in the control group, respectively (p < .05). AR expressions were increased in testis tissue significantly but were not significant in prostate tissue.Conclusions: Goji berry might improve LOH by reversing testicular dysfunction via an anti-oxidative stress mechanism without inducing prostate disease.
Asunto(s)
Hipogonadismo/tratamiento farmacológico , Lycium , Extractos Vegetales/farmacología , Testosterona/sangre , Envejecimiento , Animales , Humanos , Masculino , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Receptores Androgénicos/efectos de los fármacos , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacosRESUMEN
BACKGROUND: DA-8010 is a novel compound developed for the treatment of overactive bladder (OAB) and urinary incontinence. The aims of this study were to investigate the effects of DA-8010 on OAB in a rat model. METHODS: Study animals were divided into the following five groups of seven animals each: a sham-operated control group, a control group with partial bladder outlet obstruction (BOO) (OAB group), and three DA-8010 (doses of 0.3 mg/kg/day, 1 mg/kg/day, and 3 mg/kg/day, respectively) with partial BOO groups. Oral administration of the drugs was continued for 14 days after 2 weeks of partial BOO. After 4 weeks of partial BOO, cystometrography was performed in all groups. Additionally, pro-inflammatory cytokines, Rho-kinases, and histology of the bladder were analyzed. RESULTS: There was a significant increase in the contraction interval and a decrease in contraction pressure in the 3 mg/kg/day DA-8010 group versus those in the OAB group. Rho kinase was also significantly decreased in the DA-8010 3 mg/kg/day dosage treatment group. The increased ratio of collagen to smooth muscle after partial BOO was significantly attenuated in the DA-8010 3 mg/kg/day dosage group. CONCLUSIONS: Oral administration of DA-8010 at 3 mg/kg/day improved findings in an OAB rat model induced by partial BOO. Our results suggest that the novel muscarinic receptor antagonist DA-8010 may be a promising drug for treating patients with OAB.
Asunto(s)
Antagonistas Muscarínicos/administración & dosificación , Fenilcarbamatos/administración & dosificación , Pirrolidinas/administración & dosificación , Obstrucción del Cuello de la Vejiga Urinaria/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Administración Oral , Animales , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: This study aims to evaluate the effect of extracorporeal shock wave therapy (ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to explore the mechanism. METHODS: RWPE-2 cells were randomly divided into three groups: (a) RWPE-2 group (normal control), (b) LPS groups (lipopolysaccharide inducing inflammation) and (c) ESWT groups (LPS induced RWPE-2 treated by ESWT). After ESWT was administered, cells and supernatant were collected for enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. In vivo, Sprague-Dawley rats (n = 30) were randomly divided into three groups: (a) normal control group, (b) prostatitis groups, and (c) ESWT groups. Prostatitis rats were induced by 17 ß-estradiol and dihydrotestosterone for 4 weeks. After ESWT, prostates of each group were collected for immunohistochemistry, Western blot analysis, and ELISA. RESULTS: ESWT improved prostatitis by attenuating inflammation (P < .01). ESWT downregulated the expression of cyclooxygenase 2 (COX-2) through inhibiting TLR4-NFκB pathway compared with the LPS group in vitro or prostatitis group in vivo (P < .05). TRAF2 mediates ERK1/2-COX2 pathway. ESWT promotes prostate tissue recovery by stimulating vascular endothelial growth factor expression (P < .01). ESWT could suppress apoptosis in the prostate. CONCLUSIONS: ESWT improved CP/CPPS and reduced inflammation by degrading COX-2 in microenvironment through TLR4-NFκB-inhibiting pathway. TRAF2 regulator in ERK1/2-COX-2 inhibition significantly reduced inflammation, thus suggesting ESWT may be a potential and promising treatment for CP/CPPS.
Asunto(s)
Ciclooxigenasa 2/metabolismo , Tratamiento con Ondas de Choque Extracorpóreas , FN-kappa B/metabolismo , Prostatitis/terapia , Receptor Toll-Like 4/metabolismo , Animales , Apoptosis/fisiología , Línea Celular , Enfermedad Crónica , Regulación hacia Abajo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Masculino , FN-kappa B/antagonistas & inhibidores , Dolor Pélvico/metabolismo , Dolor Pélvico/patología , Dolor Pélvico/terapia , Prostatitis/metabolismo , Prostatitis/patología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Factor 2 Asociado a Receptor de TNF/metabolismo , Receptor Toll-Like 4/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
PURPOSE: The aim of the current trial was to assess the efficacy of on demand clomipramine 15 mg administered before sexual intercourse for the treatment of premature ejaculation. MATERIALS AND METHODS: A total of 159 patients at 5 centers in Korea were randomly assigned to 2 groups. The first group of 53 men received placebo and the second group of 106 received clomipramine 15 mg for 12 weeks. All patients were evaluated at the beginning of the study and every 4 weeks thereafter. Patients were instructed to ingest a tablet approximately 2 to 6 hours before sexual intercourse. Efficacy was assessed by scores on the IELT (Intravaginal Ejaculation Latency Time) and the PEDT (Premature Ejaculation Diagnostic Tool). RESULTS: Analyses of the IELT fold change in each group in the intent to treat population revealed that the IELT of the clomipramine 15 mg group was significantly increased 12 weeks after administration compared with the placebo group (mean ± SD 4.40 ± 5.29 vs 2.68 ± 2.03, p <0.05). The IELT fold change in the per protocol population also significantly differed between the clomipramine 15 mg group and the placebo group (mean 4.66 ± 5.64 vs 2.80 ± 2.19, p <0.05). There was a significant difference in the PEDT scores between the 2 groups (p <0.001). The most commonly reported adverse events were nausea in 15.7% of men and dizziness in 4.9%. Adverse events were mild to moderate in severity. CONCLUSIONS: The results of this multicenter, randomized, double-blind, placebo controlled, fixed dose clinical phase III study suggest that administering clomipramine 15 mg on demand to treat premature ejaculation is effective and safe.
Asunto(s)
Clomipramina/administración & dosificación , Eyaculación Prematura/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Adulto , Anciano , Método Doble Ciego , Esquema de Medicación , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: We evaluated the efficacy and safety of a combination of 2 mg tolterodine and 9 mg pilocarpine, vs tolterodine monotherapy in patients with overactive bladder. MATERIALS AND METHODS: We enrolled patients with overactive bladder symptoms in a multicenter, randomized, double-blind, parallel, active control study. Patients were randomized to the combination or 2 mg tolterodine twice daily for 12 weeks. After the double-blind period finished all patients were started on the combination for 12 weeks. Study co-primary end points were the change from baseline in the mean number of daily micturitions and cumulative incidence of dry mouth at the end of 12 weeks. Secondary end points were other overactive bladder symptoms, the total xerostomia inventory score and results of a visual analogue scale for dry mouth at the end of 12 and 24 weeks. RESULTS: The mean change in the number of daily micturitions from baseline to 12 weeks was -1.49 and -1.74 in the combination and tolterodine monotherapy groups, respectively. The mean difference was -0.26 (95% CI -0.79-0.27), confirming noninferiority. At 12 weeks the incidence of dry mouth was lower in the combination group than in the tolterodine monotherapy group (30.0% vs 42.9%, p = 0.009). All secondary and other efficacy outcomes related to overactive bladder symptoms improved in each group with no significant differences between the groups at 12 weeks. Changes from baseline in the total xerostomia inventory score and the visual analogue scale for dry mouth were significantly lower in the combination group than in the tolterodine monotherapy group. CONCLUSIONS: Tolterodine and pilocarpine alleviated dry mouth in patients with overactive bladder while maintaining anticholinergic efficacy similar to that of tolterodine.
Asunto(s)
Antagonistas Colinérgicos/administración & dosificación , Agonistas Muscarínicos/administración & dosificación , Pilocarpina/administración & dosificación , Tartrato de Tolterodina/administración & dosificación , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Xerostomía/epidemiología , Anciano , Antagonistas Colinérgicos/efectos adversos , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Agonistas Muscarínicos/efectos adversos , Pilocarpina/efectos adversos , Tartrato de Tolterodina/efectos adversos , Resultado del Tratamiento , Micción/efectos de los fármacos , Xerostomía/inducido químicamente , Xerostomía/prevención & controlRESUMEN
BACKGROUND: The purpose of this study was to report the outcomes of patients who underwent penile implantation with AMS 700 LGX inflatable penile prosthesis (IPP) in a single center by a single surgeon. METHODS: A total of 342 patients with erectile dysfunction who underwent AMS 700 LGX IPP implantation between October 2014 and April 2016 were included in this study. All patients were evaluated using the International Index of Erectile Function questionnaire preoperatively and at 3, 6, and 12 months postoperatively. We also investigated the mean stretched flaccid penile length before and after surgery as well as the complications related to and the mechanical reliability of the IPP. RESULTS: The questionnaire scores at 12 months were statistically significantly higher than the baseline scores. The mean stretched flaccid penile length was 11.1 ± 0.8 cm at baseline and was longer at 3 (11.9 ± 0.9 cm, P < 0.001), 6 (12.0 ± 0.9 cm, P < 0.001), and 12 (12.2 ± 0.7 cm, P < 0.001) postoperatively. There were no intraoperative or perioperative complications. However, one patient had infection and 10 patients developed mechanical failure during the follow-up duration. CONCLUSIONS: The results of our study suggest that the AMS 700 LGX IPP could be used to prevent penile shortening in patients undergoing IPP implantation. Furthermore, erectile function and patient satisfaction were improved excellently.
Asunto(s)
Disfunción Eréctil/epidemiología , Disfunción Eréctil/cirugía , Implantación de Pene/instrumentación , Implantación de Pene/métodos , Prótesis de Pene , Pene/cirugía , Anciano , Disfunción Eréctil/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos/fisiología , Satisfacción del Paciente , Pene/anatomía & histología , Pene/fisiología , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND: We investigated the effects of a berry mixture formula (modified Ojayeonjonghwan (Wuzi Yanzong Wan, MO formula) on detrusor overactivity (DO). METHODS: The MO formula consisted of 5 seeds obtained from 5 types of berry plants. Twenty-four Sprague-Dawley rats were randomly assigned to four groups: sham-operated (control), partial urethral obstruction-induced DO (DO group), 0.03 mg/kg solifenacin-treated DO (solifenacin group) and 200 mg/kg MO formula -treated DO (berry mixture). The control and overactive groups were administered distilled water for 4 weeks, and the solifenacin and MO formula groups were treated with the respective medication for 4 weeks. After treatment, cystometrography was performed. At the endo of cystometrography, their bladder tissues were used for identifying the muscarinic receptors, endothelial nitric oxide synthase(eNOS), RhoA, Rock-I & II, 8-hydroxy-2' -deoxyguanosine(8-OHdG), superoxide dismutase(SOD), interleukin-6 &-8(IL-6, IL-8), and tumor necrosis factor-alpha(TNF-a). The tissues were stained and the muscle-to-collagen ratio was identified. RESULTS: The presence of the muscarinic receptors were not significantly different between the solifenacin and MO formula groups. However, significant differences were found between the solifenacin and MO formula groups in terms of eNOS, RhoA, Rock-I and -II levels. The muscle-to-collagen ratio was statistically lower in the DO and solifenacin groups; however, no significant difference was observed between the control and MO formula groups. Under oxidative stress, SOD showed a similar result as 8-OHgG. The MO formula group exhibited anti-inflammatory effects, showing that no significant difference was found between the control and MO formula groups regarding values of IL-6, IL-8, and TNF-a. However, the DO and solifenacin groups showed increased IL-6, IL-8, and TNF-a levels. Cystometrography showed that the OAB and solifenacin groups having a significantly lower value than the control and MO formula groups. The mean contraction interval was shorter in the DO, MO formula, and solifenacin groups and the highest in the control group. CONCLUSIONS: The MO formula exhibited a similar pharmacologic effect to that of solifenacin, with anti-inflammatory and antioxidant effects. Enhancement of the MO formula by the nitric oxide pathway affected DO including BPH-related DO. The MO formula may be one of the alternative choices of anticholinergics, a treatment for DO.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Obstrucción Uretral/metabolismo , Vejiga Urinaria Hiperactiva/metabolismo , Animales , Antiinflamatorios/farmacología , Femenino , Ratas , Ratas Sprague-Dawley , Receptores Muscarínicos/metabolismo , Vejiga Urinaria/efectos de los fármacosRESUMEN
PURPOSE: To compare the clinical outcomes of laparoendoscopic single-site plus one-port donor nephrectomy (LESSOP-DN) and mini laparoscopic donor nephrectomy (MLDN). METHODS: A prospective randomized controlled trial was conducted from December 2014 to February 2016 in donors scheduled for left donor nephrectomy. Donor and recipient demographics and clinical outcomes including pain scores and questionnaires (BIQ: body image questionnaire, SF-36, patient-reported overall convalescence) were also compared. RESULTS: A total of 121 eligible donors were recruited, of which 99 donors who were scheduled to undergo an operation on their left side were randomized into LESSOP-DN (n = 50) and MLDN (n = 49) groups. There were no significant demographic differences between the two groups. The renal extraction time in the LESS-DN group was shorter than that in the MLDN group (75.89 ± 13.01 vs. 87.31 ± 11.38 min, p < 0.001). Other perioperative parameters and complication rates were comparable between the two groups. The LESSOP-DN group had a smaller incision length than the MLDN group (4.89 ± 0.68 vs. 6.21 ± 1.11 cm, p < 0.001), but cosmetic scores and body image scores were similar in the two groups (p = 0.905, 0.217). Donor quality of life (SF-36) and recovery and satisfaction data were comparable between the two groups. Delayed graft function (DGF) occurred in one recipient undergoing MLDN procedure (2.1%) and progressed to graft failure. CONCLUSIONS: There were no differences in cosmetic satisfaction between groups despite the smaller incision size of LESSOP-DN. Safety parameters and subjective measures of postoperative morbidity were similar between the two groups.
Asunto(s)
Pérdida de Sangre Quirúrgica/prevención & control , Laparoscopía , Procedimientos Quirúrgicos Mínimamente Invasivos , Nefrectomía , Dolor Postoperatorio , Calidad de Vida , Adulto , Femenino , Humanos , Trasplante de Riñón/métodos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Tiempo de Internación/estadística & datos numéricos , Donadores Vivos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/psicología , Nefrectomía/efectos adversos , Nefrectomía/métodos , Tempo Operativo , Evaluación de Resultado en la Atención de Salud , Dimensión del Dolor , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Recolección de Tejidos y Órganos/métodosRESUMEN
Effective therapies for erectile dysfunction (ED) associated with diabetes mellitus (DM) are needed. In this study, the effects of stromal cell-derived factor-1 (SDF-1)-expressing engineered mesenchymal stem cells (SDF-1 eMSCs) and the relevant mechanisms in the corpus cavernosum of a streptozotocin (STZ)-induced DM ED rat model were evaluated. In a randomized controlled trial, Spragueâ»Dawley (SD) rats (n = 48) were divided into four groups (n = 12/group): Normal (control), DM ED (diabetes induced by STZ), DM ED + BM-MSC (treated with bone marrow [BM]-derived MSCs), and DM ED + SDF-1 eMSC (treated with SDF-1-expressing BM-MSCs). After four weeks, intracavernosal pressure (ICP), an indicator of erectile function, was 0.75 ± 0.07 in the normal group, 0.27 ± 0.08 in the DM ED group, 0.42 ± 0.11 in the DM ED + BM-MSC group, and 0.58 ± 0.11 in the DM ED + SDF-1 eMSC group. BM-MSCs, especially SDF-1 eMSCs, improved ED (p < 0.05). SDF-1 eMSC treatment improved the smooth muscle content in the corpus cavernosum (p < 0.05). As SDF-1 expression increased, ED recovery improved. In the SDF-1 eMSC group, levels of neuronal nitric oxide synthase (nNOS) and phosphorylated endothelial NOS (p-eNOS) were higher than those in other groups (p < 0.05). In addition, high stromal cell-derived factor-1 (SDF-1) expression was associated with increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in DM ED rats (p < 0.05). Higher levels of phosphorylated protein kinase B (p-AKT)/protein kinase B (AKT) (p < 0.05) and B-cell lymphoma-2 (Bcl-2) and lower levels of the apoptosis factors Bcl2-associated x (Bax) and caspase-3 were observed in the MSC-treated group than in the DM ED group (p < 0.05). SDF-1 eMSCs showed beneficial effects on recovery from erectile function.
Asunto(s)
Quimiocina CXCL12/genética , Disfunción Eréctil/genética , Expresión Génica , Ingeniería Genética , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Animales , Glucemia , Peso Corporal , Movimiento Celular/genética , Diabetes Mellitus Experimental , Modelos Animales de Enfermedad , Disfunción Eréctil/terapia , Masculino , Neovascularización Fisiológica , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Transducción de SeñalRESUMEN
BACKGROUND: Phosphodiesterase type 5 inhibitors and α-adrenergic blocking agents (α-blockers) are widely used for the treatment of erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). AIMS: To assess the efficacy and safety of fixed-dose combinations (FDCs) of tamsulosin and tadalafil compared with tadalafil monotherapy in patients with comorbid BPH-associated LUTS and ED. METHODS: A randomized, double-blinded, active-controlled trial was conducted of 510 men with BPH-associated LUTS and ED. Patients were treated with FDCs of tamsulosin 0.4 mg plus tadalafil 5 mg (FDC 0.4/5 mg), tamsulosin 0.2 mg plus tadalafil 5 mg (FDC 0.2/5 mg), or tadalafil 5 mg for a 12-week treatment period. For a subsequent 12-week extension period, the patients were administered FDC 0.4/5 mg. OUTCOMES: The primary outcomes were changes from baseline in total International Prostate Symptom Score (IPSS) and International Index of Erectile Function erectile function domain (IIEF-EF) score at week 12 to prove superiority and non-inferiority of FDCs compared with tadalafil 5 mg. The safety assessments were adverse reactions, laboratory test results, and vital signs at week 24. RESULTS: The mean changes in total IPSS and IIEF-EF scores were -9.46 and 9.17 for FDC 0.4/5 mg and -8.14 and 9.49 for tadalafil 5 mg, respectively, which indicated superiority in LUTS improvement (P = .0320) and non-inferiority in ED treatment with FDC 0.4/5 mg compared with tadalafil 5 mg. However, the results from FDC 0.2/5 mg failed to demonstrate superiority in LUTS improvement. No clinically significant adverse events regarding the investigational products were observed during the 24-week period. CLINICAL IMPLICATIONS: The FDC 0.4/5 mg is the first combined formulation of an α-blocker and a phosphodiesterase type 5 inhibitor that offers benefits in patient compliance and as add-on therapy in patients with comorbid BPH-associated LUTS and ED. STRENGTHS AND LIMITATIONS: The study clearly demonstrated the advantage of FDC 0.4/5 mg. The main advantage of FDC 0.4/5 mg was the enhanced efficacy on BPH-associated LUTS comorbidity with ED, the lower incidence of side effects, and the simplification and convenience of therapy, which led to better overall patient compliance. However, the lack of a tamsulosin monotherapy control group was a limitation of this study. CONCLUSION: The FDC 0.4/5 mg therapy was safe, well tolerated, and efficacious, indicating that combination therapy could provide clinical benefits for patients with BPH-associated LUTS complaints and ameliorate the comorbidity of ED. Kim SW, Park NC, Lee SW, et al. Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial. J Sex Med 2017;14:1018-1027.
Asunto(s)
Disfunción Eréctil/tratamiento farmacológico , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Tadalafilo/administración & dosificación , Agentes Urológicos/administración & dosificación , Anciano , Terapia Combinada , Método Doble Ciego , Quimioterapia Combinada , Disfunción Eréctil/etiología , Disfunción Eréctil/fisiopatología , Humanos , Síntomas del Sistema Urinario Inferior/etiología , Síntomas del Sistema Urinario Inferior/fisiopatología , Masculino , Persona de Mediana Edad , Inhibidores de Fosfodiesterasa 5/administración & dosificación , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Hiperplasia Prostática/complicaciones , Sulfonamidas/efectos adversos , Tadalafilo/efectos adversos , Tamsulosina , Resultado del Tratamiento , Agentes Urológicos/efectos adversosRESUMEN
PURPOSE: To investigate the factors predictive of surgical outcomes of tubeless percutaneous nephrolithotomy (TPCNL) and to compare the predictability and accuracy of the Guy's stone score, S.T.O.N.E. nephrolithometry, and CROES nomogram. PATIENTS AND METHODS: We reviewed retrospectively the surgical outcomes recorded consecutively and imaging data of preoperative computed tomography scans of 141 patients who had undergone TPCNL from June 2012 to October 2015. Guy's, S.T.O.N.E., and CROES stone-scoring systems (SSSs) and other prognostic factors were assessed using univariate and multivariate statistical analyses. RESULTS: The initial stone-free and complication rates after TPCNL were 78.7 (111/141) and 17.0 % (24/141). On univariate analysis, all three scoring systems were identified as significant factors in terms of stone-free rate (SFR). The multivariate logistic regression analysis showed that the Guy's stone score and stone burden ≥385 mm2 had significant correlations with stone-free status [odds ratios (OR) = 3.220, p = 0.001 and OR = 6.451, p = 0.002, respectively]. Guy's stone score (OR = 1.879, p = 0.013) was an independent risk factor for the development of complications. The area under the receiver operating characteristic (ROC) curves for the Guy's, S.T.O.N.E., and CROES SSSs and stone burden showed good results (0.821, 0.816, 0.820, and 0.800, respectively). Pairwise comparison of ROC curves showed that there was no significant difference between each final score and stone burden. CONCLUSIONS: Of the three scoring systems, Guy's stone score was the only significant predictive factor for SFR and complication rates after TPCNL in the multivariate logistic regression analysis. Stone burden was significantly associated with a postoperative stone-free status (SFS).
Asunto(s)
Cálculos Renales/cirugía , Nefrostomía Percutánea/métodos , Nomogramas , Adulto , Anciano , Femenino , Humanos , Cálculos Renales/diagnóstico por imagen , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Curva ROC , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
A multi-center, randomized, double-blind, placebo-controlled study was conducted with 158 subjects who were randomized to placebo or avanafil 50, 100, and 200 mg on demand for 8 weeks to evaluate the safety, tolerability, and efficacy of avanafil in the treatment of erectile dysfunction (ED) in Korean men. The primary outcome was the erectile function (EF) domain score of the International Index of Erectile Function (IIEF) questionnaire. Secondary outcomes included changes in the scores of IIEF questions 3 and 4 (IIEF Q3, Q4) from baseline, changes in all domain scores in the IIEF from baseline, Sexual Encounter Profile questions 2-5 (SEP2-5), the Global Efficacy Assessment Question (GEAQ), and the number of subjects whose EF domain score at the 8th week visit was ≥ 26. After 8 weeks of treatment, the dose groups except avanafil 50 mg scored significantly higher on the IIEF-EF domain from baseline than the placebo group. The changes from baseline in the avanafil group in IIEF Q3 (all doses) and Q4 (200 mg alone) were higher than the placebo group. The differences between avanafil and placebo groups were significant in SEP2 (100 and 200 mg) and SEP3-5 (200 mg). The differences in the GEAQ "Yes" response were also significant in the avanafil 100 and 200 mg groups. Regarding the ratio of normal EF at the end of the study, avanafil 200 mg differed significantly from the placebo. Most treatment-associated adverse events were mild and resolved spontaneously. This is a clinical trial study and was registered at www.ClinicalTrials.gov (Identifier: NCT02477436).
Asunto(s)
Disfunción Eréctil/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Pirimidinas/uso terapéutico , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Erección Peniana/efectos de los fármacos , Efecto Placebo , Pirimidinas/farmacología , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
BACKGROUND: Houttuynia cordata Thunb (HC) is a traditional herbal medicine widely used in Asia for the treatment of patients with alopecia, usually in combination with other two herbal medicines (Perilla frutescens var. acuta (PFVA) and green tea (GT)). However, the effect of this herbal complex has not been clearly demonstrated. We sought to determine the hair growth-promoting effect of this herbal complex (HC, PFVA, and GT) in the animal model. METHODS: Six-week-old male C57BL/6 mice were randomly divided into four groups (negative control, finasteride (1 mg/kg) as a positive control, and two (200 and 400 mg/kg) concentrations of the herbal complex as experimental groups) and were fed its corresponding medications orally for 25 days. Hair growth was evaluated visually and microscopically. Western blot analysis for insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-ß1 was performed. RESULTS: The herbal complex exhibited hair growth-promoting activity in C57BL/6 mice. Grossly, the area of hair regrowth was 55.1 (±3.8) %, 70.2 (±6.3) % and 83.5 (±5.7) % in negative control, herbal complex 200 mg/kg and 400 mg/kg group, respectively. In histologic examination, the hair follicle count in deep subcutis was 2.6 (±0.7), 5.8 (±0.7) and 8.6 (±1.2) and the diameter of hair follicles was 11.9 (±5.0) µm, 17.4 (±3.9) µm and 22.8 (±5.2) µm in negative control, herbal complex 200 and 400 mg/kg group, respectively. The expression of IGF-1 was 0.14 (±0.01), 0.23 (±0.02) and 0.24 (±0.01) and the expression of TGF-ß1 was 0.26 (±0.01), 0.19 (±0.02) and 0.15 (±0.01) in negative control, the 200 and 400 mg/kg group, respectively. CONCLUSIONS: This data provides adequate preliminary experimental evidence to support the hair regeneration effect of this herbal complex.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Cabello/efectos de los fármacos , Houttuynia , Perilla frutescens , Té , Animales , Finasterida/farmacología , Folículo Piloso/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Hypercholesterolaemia (HC) is a major risk factor for ischemic heart disease and is also known to be a risk factor for erectile dysfunction (ED). ED caused by HC is thought to be related to HC-induced oxidative stress damage in the vascular endothelium and erectile tissue. KH-204 is an herbal formula with a strong antioxidant effect. We evaluated the effects of KH-204 on erectile function in a rat model of HC-induced ED. METHODS: Male Sprague-Dawley rats (6 weeks old) were divided into normal control, high-fat and cholesterol diet (HFC), and HFC with KH-204 treatment (HFC + KH) groups (n = 12 each). Normal control group rats were fed normal chow diet. HFC and HFC + KH group rats were fed high-fat and cholesterol diets and treated with or without daily oral doses of KH-204 for 12 weeks. Subsequently, intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured, and lipid profiles, expression of endothelial (eNOS) and neuronal (nNOS) nitric oxide synthase, oxidative stress (8-hydroxy-2-deoxyguanosine), and ratio of smooth muscle cells and collagen fibres were evaluated in the serum and corpora tissue. RESULTS: Compared to the HFC group, the HFC + KH group showed statistically significant increases in peak ICP and ICP/MAP ratio, expression of eNOS and nNOS, and ratio of smooth muscle cells and collagen fibres (p < 0.05). The HFC + KH group also showed statistically significant decreases in oxidative stress (p < 0.05). Further the lipid profiles of this group were ameliorated compared to those of the HFC group (p < 0.05). CONCLUSIONS: The current study shows that the antioxidant and hypolipidemic effects of KH-204 are effective in ameliorating ED by restoring endothelial dysfunction and suggests that KH-204 may be a potential therapeutic agent for ED by correcting the fundamental cause of ED.
Asunto(s)
Disfunción Eréctil/prevención & control , Hipercolesterolemia/complicaciones , Erección Peniana/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Animales , Biomarcadores/análisis , Peso Corporal/efectos de los fármacos , Modelos Animales de Enfermedad , Disfunción Eréctil/etiología , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Magnoliopsida/química , Masculino , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo/efectos de los fármacos , Pene/efectos de los fármacos , Pene/enzimología , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratas Sprague-DawleyRESUMEN
PURPOSE: We determined the effect of testosterone solution 2% on total testosterone level and the 2 symptoms of hypogonadism, sex drive and energy level. MATERIALS AND METHODS: This was a randomized, multicenter, double-blind, placebo controlled, 16-week study to compare the effect of testosterone and placebo on the proportion of men with a testosterone level within the normal range (300 to 1,050 ng/dl) upon treatment completion. We also assessed the impact of testosterone on sex drive and energy level measured using SAID (Sexual Arousal, Interest and Drive scale) and HED (Hypogonadism Energy Diary), respectively. A total of 715 males 18 years old or older with total testosterone less than 300 ng/dl and at least 1 symptom of testosterone deficiency (decreased energy and/or decreased sexual drive) were randomized to 60 mg topical testosterone solution 2% or placebo once daily. RESULTS: Of study completers 73% in the testosterone vs 15% in the placebo group had a testosterone level within the normal range at study end point (p <0.001). Participants assigned to testosterone showed greater baseline to end point improvement in SAID scores (low sex drive subset p <0.001 vs placebo) and HED scores (low energy subset p = 0.02 vs placebo, not significant at prespecified p <0.01). No major adverse cardiovascular or venous thrombotic events were reported in the testosterone group. The incidence of increased hematocrit was higher with testosterone vs placebo (p = 0.04). CONCLUSIONS: Once daily testosterone solution 2% for 12 weeks was efficacious in restoring normal testosterone levels and improving sexual drive in hypogonadal men. Improvement was also seen in energy levels on HED though not at the prespecified p <0.01. No new safety signals were identified.