Testosterone and dihydrotestosterone modulate the redox homeostasis of endothelium.

The predominance of cardiovascular diseases among men compared to premenopausal women has been attributed to testosterone, which is implicated in vascular remodeling. Molecular mechanisms underlying its role have not been clarified but oxidative stress-induced inflammation may be important. We therefore investigated in vitro the effects of testosterone and dihydrotestosterone, (a nonaromatized androgen), on redox homeostasis in absence (basal conditions) and after corticotropin-releasing hormone-induced pro-oxidant action in macroendothelial cells. More specifically, we explored their role on well-established antioxidant enzymes activity, namely endothelial nitric oxide synthase, superoxide dismutase, catalase, and glutathione. We observed that both androgens significantly increased the intracellular reactive oxygen species levels, endothelial nitric oxide synthase activity, nitric oxide concentration as well as superoxide dismutase activity and decreased catalase activity. These effects of Testosterone and DHT were reversed in the presence of the androgen receptor antagonist, flutamide. Moreover, testosterone and dihydrotestosterone similarly enhanced the stimulatory effect of corticotropin-releasing hormone on intracellular reactive oxygen species levels and superoxide dismutase activity but did not influence the inhibitory effect on endothelial nitric oxide synthase activity, nitric oxide release and catalase activity. Finally, androgens did not have a detectable effect on glutathione levels or the glutathione/glutathione plus glutathione disulfide ratio. Our results reveal that testosterone and DHT rise the intracellular redox threshold of the endothelial cell and increases NO synthesis. These findings suggest that the action of testosterone is affected by the redox status of the endothelium and help to explain its controversial effects on the cardiovascular system.

Translation and Validation of the TANGO Nocturia Screening Tool into Greek.

PURPOSE: The present study aimed to translate the Targeting the individual's Aetiology of Nocturia to Guide Outcomes Questionnaire (TANGO) into the Greek language to create TANGO-Gr. A relative reliability study in prospective samples of community dwellers and rehabilitation centre residents was undertaken in order to validate the translation. In terms of nocturia severity, these groups were considered to be representative of patients at both ends of the scale, and therefore suitable validation purposes. PATIENTS AND METHODS: The prospective descriptive study took place between 07 and 09/2020. Fifty residents in a rehabilitation centre and thirty-seven community dwellers were included in the study. All participants had more than one episode of nocturia per night. They were asked to complete the newly translated TANGO-Gr Questionnaire twice (test-retest procedure). TANGO-Gr includes three possible answers ("yes", "no", and "DK/NA") to facilitate increased validity. The study group evaluated the socio and demographic characteristics, the level of independence and the comprehensive frailty of all participants. RESULTS: Both groups satisfactorily completed questionnaire responses. The overall Cronbach's alpha coefficient was 0.753 (community-dwelling people: 0.776; rehabilitation centre residents: 0.531). A test-retest statistical analysis to determine reliability found an overall median Kappa of 0.88 (IQR: 0.79-0.94) in community dwellers and 0.91 (IQR: 0.84-1.00) in rehabilitation centre residents, thereby confirming an almost perfect respective agreement. CONCLUSION: The validity of the newly translated TANGO-Gr Questionnaire was proven. It should be considered to be a reliable, self-administered screening tool suitable for clinical practice, and therefore invaluable for Greek-speaking people. The study also determined that certain environment-related variables may contribute to nocturia in rehabilitation centre populations, which is a finding which invites further study.

Mirabegron Alleviates the Degree of Burden Experienced by Caregivers of Older Females with Mixed or Urge Incontinence: A Prospective Study.

PURPOSE: Older people, especially women, have the highest known prevalence of urinary incontinence (UI) of any other age-group. Continual care provision for elderly incontinent females is an incredibly arduous process, yet only very few studies have investigated the issue. Aim of the study was to evaluate the impact of mirabegron's treatment on the degree of burden experienced by caregivers of elderly female patients with UI. PATIENTS AND METHODS: A hundred and eighty-six caregivers of older females with mixed or urgency UI besides various conditions (strokes, post-operative recovery after major surgery, etc.) were included in the study. Group A comprised 91 patients that did not want to receive any treatment for UI. Group B consisted of 95 elderly females treated for UI with mirabegron 50 mg/daily for three months. All caregivers completed the Zarit Burden Scale (ZBS) questionnaire at the outset and after the three months. All patients completed a bladder diary at the beginning and at the end of the observation/medication period. RESULTS: Patients receiving mirabegron presented a statistically significant improvement in UI parameters. Their caregivers showed a statistically significant decrease in the ZBS total score as well as separate domains. CONCLUSION: This pilot study confirms that mirabegron administration can improve the quality of life of older females suffering from UI while substantially relieving caregiver burden. Recognizing the physical and emotional reactions of caregivers may help health providers deliver better support and resources to meet the needs of caregivers and patients alike.

Transurethral resection of a bladder trigone leiomyoma: a rare case report.

BACKGROUND: Bladder leiomyomas are rare and benign tumors of the bladder. They account for 0.43% of all bladder tumors, and only 250 cases have been reported in English literature. Based on the size and localization of the lesion, their symptoms vary considerably. Women seem to be more affected, and obstructive symptoms predominate. Surgical treatment is almost always highly effective, leaving a low recurrence rate. CASE PRESENTATION: We present a clinical case of a 52-year old man with macroscopic hematuria and obstructive lower urinary tract symptoms due to a large bladder trigone leiomyoma. CT and MRI showed a well-defined large bladder leiomyoma and cystoscopy established the initial findings. The patient underwent successful transurethral resection of the lesion, and pathology findings confirmed the diagnosis. CONCLUSIONS: This case report demonstrates that transurethral resection of a large bladder trigone leiomyoma is a feasible and successful procedure. Long term follow-up proves that there is neither scarring distortion of the bladder trigone area nor damage in the ureteral orifices, even though there was a thorough removal of the trigone wall.

17-ß estradiol attenuates the pro-oxidant activity of corticotropin-releasing hormone in macroendothelial cells.

Corticotropin-releasing hormone, which is the predominant regulator of neuroendocrine responses to stress, attenuates inflammation through stimulation of glucocorticoid release. Enhanced corticotropin-releasing hormone expression has been detected in inflammatory cells of the vascular endothelium, where it acts as a local regulator of endothelial redox homeostasis. Estrogens have beneficial effects on endothelial integrity and function, though the mechanism underlying their antioxidative effect remains as yet largely unknown. We therefore investigated the effect of 17ß-estradiol on pro-oxidant action of corticotropin-releasing hormone in vitro in macroendothelial cells, and, more specifically, the role of 17ß-estradiol on corticotropin-releasing hormone-induced activities/release of the antioxidant enzymes namely, endothelial nitric oxide synthase, superoxide dismutase, catalase, and glutathione. We observed that 17ß-estradiol abolished the stimulatory effect of corticotropin-releasing hormone on intracellular reactive oxygen species levels and counteracted its inhibitory effect on endothelial nitric oxide synthase activity and nitric oxide release. In addition, 17ß-estradiol significantly induced superoxide dismutase and catalase activity, an effect that was not significantly influenced by corticotropin-releasing hormone. Finally, 17ß-estradiol significantly increased glutathione levels and the glutathione/glutathione + glutathione disulfide ratio, an action that was partially blocked by corticotropin-releasing hormone. Our results reveal that 17ß-estradiol counterbalances corticotropin-releasing hormone-mediated pro-inflammatory action and thereby maintains the physiological threshold of the endothelial cell redox environment. These observations may be of importance, considering the protective role of estrogen in the development of atherosclerosis.

Effective treatment of neurogenic detrusor overactivity in multiple sclerosis patients using desmopressin and mirabegron.

INTRODUCTION: Multiple sclerosis (MS) is the commonest progressive neurological disease affecting young people. With advancing disease, management of neurogenic detrusor overactivity (NDO) based on antimuscarinics may prove inadequate and if based on botulinum toxin, may necessitate clean intermittent self-catheterization. The aim of the study was to evaluate the effectiveness of combined mirabegron and desmopressin administration in the treatment of NDO in patients with MS. MATERIALS AND METHODS: Sixty patients diagnosed with MS and NDO were evaluated. All had received treatment with solifenacin 10 mg/daily for 3 months and were displeased with the results. Patients were divided in four groups. In Group A (n = 15) patients continued receiving solifenacin 10 mg/daily; in Group B (n = 15) patients received mirabegron 50 mg/daily; in Group C (n = 15) patients received desmopressin 120 mcg/daily and in Group D (n = 15) patients received mirabegron 50 mg/daily and desmopressin 120 mcg/daily. All patients were assessed with a 3 day bladder diary at the beginning and at the end of the treatment. RESULTS: All patients in Groups A, B and C did not demonstrate statistically significant changes at the end of the treatment period in their 3 day bladder diary and in the presence of urinary infections. In Group D, a statistically significant improvement was noted in the mean change from baseline to end of treatment in micturition episodes (3.5 +/- 0.4 micturition/24h), in urgency episodes (2.3 +/- 0.2) and mean number of urinary incontinence (1.0 +/- 0.2 episodes/24h). CONCLUSIONS: Treatment with mirabegron and desmopressin revealed both effectiveness and safety in patients with NDO and MS.

The effect of extended release tolterodine used for overactive bladder treatment on female sexual function

ABSTRACT Introduction Overactive bladder (OAB) is a common condition, especially in middle aged women, requiring long term therapy with anticholinergics to maintain symptoms relief. The aim of the study was to determine the effect of tolterodine extended release (ER) used for OAB treatment on the sexual function of women. Materials and Methods Between August 2010 and August 2014, 220 women with confirmed OAB, attended Urogynecology Outpatient Clinic and were prospectively enrolled in this study. 158 women were evaluated, with a comprehensive history, physical examination, urodynamic studies and Female Sexual Function Index (FSFI) questionnaire. 73 patients of group A (control group) received no treatment and 85 patients of group B received an anticholinergic regimen - tolterodine ER 4mg once daily. Data were evaluated again in accordance with FSFI after three months, using SPSS software. Results A statistically significant increase was noted in group B in domains of desire (pre-treatment 2.5±0.2 to 4.5±0.2 post-treatment), arousal (3.1±0.2 to 3.1±0.2 respectively), lubrication (3.4±0.3 to 4.3±0.3 respectively), orgasm (3.5±0.3 to 4.5±0.3 respectively), satisfaction (2.6±0.2 to 4.2±0.3 respectively) and pain (2.4±0.2 to 4.6±0.4 respectively) after three months treatment with tolterodine ER. In group A there were no statistically significant changes in pre and post treatment values (p>0.05). Total FSFI score for group B was significantly higher after tolterodine treatment (26.5±1.5) compared to pre-treatment values (17.4±1.4, p<0.01) and to control group A (17.7±1.2 and 17.9±1.5, p>0,05) respectively. Conclusions This preliminary study demonstrates that treatment of OAB with tolterodine ER was found to have positive effect on sexual function of patients with OAB.

The effect of extended release tolterodine used for overactive bladder treatment on female sexual function.

INTRODUCTION: Overactive bladder (OAB) is a common condition, especially in middle aged women, requiring long term therapy with anticholinergics to maintain symptoms relief. The aim of the study was to determine the effect of tolterodine extended release (ER) used for OAB treatment on the sexual function of women. MATERIALS AND METHODS: Between August 2010 and August 2014, 220 women with confirmed OAB, attended Urogynecology Outpatient Clinic and were prospectively enrolled in this study. 158 women were evaluated, with a comprehensive history, physical examination, urodynamic studies and Female Sexual Function Index (FSFI) questionnaire. 73 patients of group A (control group) received no treatment and 85 patients of group B received an anticholinergic regimen - tolterodine ER 4mg once daily. Data were evaluated again in accordance with FSFI after three months, using SPSS software. RESULTS: A statistically significant increase was noted in group B in domains of desire (pre-treatment 2.5±0.2 to 4.5±0.2 post-treatment), arousal (3.1±0.2 to 3.1±0.2 respectively), lubrication (3.4±0.3 to 4.3±0.3 respectively), orgasm (3.5±0.3 to 4.5±0.3 respectively), satisfaction (2.6±0.2 to 4.2±0.3 respectively) and pain (2.4±0.2 to 4.6±0.4 respectively) after three months treatment with tolterodine ER. In group A there were no statistically significant changes in pre and post treatment values (p>0.05). Total FSFI score for group B was significantly higher after tolterodine treatment (26.5±1.5) compared to pre-treatment values (17.4±1.4, p<0.01) and to control group A (17.7±1.2 and 17.9±1.5, p>0,05) respectively. CONCLUSIONS: This preliminary study demonstrates that treatment of OAB with tolterodine ER was found to have positive effect on sexual function of patients with OAB.