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111.
112.
Impairment of sphincter muscles or their neural and vascular support leads to stress urinary incontinence. The aim of this study was to determine the role of urine-derived stem cells (USCs) over-expressing vascular endothelial growth factor (VEGF) in collagen-I gel on angiogenesis, cell survival, cell growth, myogenic phenotype differentiation of the implanted cells and innervations following implantation in vivo. USCs were infected with adenovirus containing the human VEGF165 and green fluorescent protein genes. A total of 5 × 106 cells, USCs alone, or plus endothelial cells or human skeletal myoblasts (as control) suspended in collagen-I gel were subcutaneously implanted into nude mice. Extensive vascularization and more implanted cells was noted in VEGF-expressing USCs groups compared to the non-VEGF groups in vivo. Numbers of the cells displaying endothelial markers (CD 31 and von Willebrand's factor) and myogenic markers (myf-5, MyoD and desmin), and regenerated nerve fibers displaying neural markers (S-100, GFAP and neurofilament) significantly increased in the grafts of VEGF-expressing USCs. Improved angiogenesis by VEGF-expressing USCs enhanced grafted cell survival, recruited the resident cells and promoted myogenic phenotype differentiation of USCs and innervation. This approach has important clinical implications for the development of cell therapies for the correction of stress urinary incontinence. 相似文献
113.
Nishimune A Yoshiki H Uwada J Anisuzzaman AS Umada H Muramatsu I 《British journal of pharmacology》2012,165(5):1226-1234
α(1)-Adrenoceptors are involved in numerous physiological functions, including micturition. However, the pharmacological profile of the α(1)-adrenoceptor subtypes remains controversial. Here, we review the literature regarding α(1)-adrenoceptors in the lower urinary tract from the standpoint of α(1L) phenotype pharmacology. Among three α(1)-adrenoceptor subtypes (α(1A), α(1B) and α(1D)), α(1a)-adrenoceptor mRNA is the most abundantly transcribed in the prostate, urethra and bladder neck of many species, including humans. In prostate homogenates or membrane preparations, α(1A)-adrenoceptors with high affinity for prazosin have been detected as radioligand binding sites. Functional α(1)-adrenoceptors in the prostate, urethra and bladder neck have low affinity for prazosin, suggesting the presence of an atypical α(1)-adrenoceptor phenotype (designated as α(1L)). The α(1L)-adrenoceptor occurs as a distinct binding entity from the α(1A)-adrenoceptor in intact segments of variety of tissues including prostate. Both the α(1L)- and α(1A)-adrenoceptors are specifically absent from Adra1A (α(1a)) gene-knockout mice. Transfection of α(1a)-adrenoceptor cDNA predominantly expresses α(1A)-phenotype in several cultured cell lines. However, in CHO cells, such transfection expresses α(1L)- and α(1A)-phenotypes. Under intact cell conditions, the α(1L)-phenotype is predominant when co-expressed with the receptor interacting protein, CRELD1α. In summary, recent pharmacological studies reveal that two distinct α(1)-adrenoceptor phenotypes (α(1A) and α(1L)) originate from a single Adra1A (α(1a)-adrenoceptor) gene, but adrenergic contractions in the lower urinary tract are predominantly mediated via the α(1L)-adrenoceptor. From the standpoint of phenotype pharmacology, it is likely that phenotype-based subtypes such as the α(1L)-adrenoceptor will become new targets for drug development and pharmacotherapy. 相似文献
114.
Duloxetine for the treatment of stress urinary incontinence in women: an integrated analysis of safety 总被引:1,自引:0,他引:1
Hurley DJ Turner CL Yalcin I Viktrup L Baygani SK 《European journal of obstetrics, gynecology, and reproductive biology》2006,125(1):120-128
OBJECTIVE: The objective was to characterize the safety of duloxetine for treatment of stress urinary incontinence (SUI) in women, using an integrated database generated from four published placebo-controlled clinical trials. METHODS: The database included 1913 women randomized to duloxetine (N=958) or placebo (N=955), examining adverse events (AEs), serious adverse events (SAEs), vital signs, electrocardiograms, and laboratory analytes. AEs occurring initially or worsening during the double-blind treatment period were considered treatment-emergent (TEAE). Differences between duloxetine-treated and placebo-treated groups were compared statistically. RESULTS: Common TEAEs included: nausea (23.2%), dry mouth (13.4%), fatigue (12.7%), insomnia (12.6%), constipation (11.0%), headache (9.7%), dizziness (9.5%), somnolence (6.8%), and diarrhea (5.1%). Most TEAEs that emerged early were mild to moderate, rarely worsened, and resolved quickly. Overall AE discontinuation rates were 20.5% for duloxetine and 3.9% for placebo (P<.001). Most discontinuations (83%) occurred within the first month of treatment. SAEs were uncommon and did not differ between treatments. Statistically significant, but clinically unimportant mean increases in heart rate (2.4 bpm) and systolic and diastolic blood pressure (相似文献
115.
Introduction and hypothesis The aim of the study was to assess the quality of life (QoL) in women with stress urinary incontinence (SUI) while using a
novel disposable intravaginal device.
Methods Fifty women with severe SUI who completed a 7-day control period followed by a 28-day device usage period underwent QoL assessments
based on two validated questionnaires, the Incontinence Impact Questionnaire (IIQ-7) and the Urogenital Distress Inventory
(UDI-6).
Results Mean total score for the IIQ-7 decreased from 41.8 ± 24.1 to 4.4 ± 8.7 at the pre- and poststudy visits, respectively (P < 0.001). The mean total score for the UDI-6 decreased from 48.2 ± 16.1 to 11.5 ± 11.9 at the pre- and poststudy visits,
respectively (P < 0.001). Statistically significant decreases in most subscale scores were observed by the end of the study for both questionnaires
(all P values <0.001).
Conclusion The novel disposable intravaginal device significantly improved QoL in women with SUI. 相似文献