Long-term efficacy of a vaginal sling procedure in a rat model of stress urinary incontinence

PURPOSE: We examined the long-term efficacy of a newly created vaginal sling procedure for the restoration of leak point pressure (LPP) in a rat model of stress urinary incontinence (SUI). MATERIAL AND METHODS: A total of 20 female Sprague-Dawley rats were randomly assigned to 1 of 4 groups, namely normal control, SUI plus vaginal sling, SUI plus sham sling and SUI only. SUI was created in the latter 3 groups by bilateral pudendal nerve transection (PNT). In the sling procedure a 2 x 0.3 cm strip of polypropylene mesh was placed at the mid urethral level. Animals in the SUI plus sham sling group underwent vaginal dissection only. After 5 weeks LPP was measured 4 or 5 times in each rat and the mean was determined. The Kruskal-Wallis and Wilcoxon rank sum tests were used to evaluate whether levels of measurements differed across and between groups. RESULTS: Mean LPP +/- SD in control rats was 48.8 +/- 10.2 cm H2O. PNT decreased LPP to 23.5 +/- 7.4 cm H2O. Sling placement improved LPP at 5 weeks to 35.5 +/- 2.3 cm H2O, whereas LPP in the sham sling group was 29.1 +/- 4.9 cm H2O. LPP recovery in the sling group was significantly above levels for PNT (p = 0.037). LPP in the sling group did not differ statistically from that in the control group (p = 0.11). CONCLUSIONS: The newly created vaginal sling model restores the LPP in the rat model of SUI in the long term (5 weeks). This model could be used to address research questions related to the sling procedure.     

Role of sling integrity in the restoration of leak point pressure in the rat vaginal sling model

PURPOSE: We tested the hypothesis that cutting the sling at its suburethral section does not cancel its anti-incontinence effect. We also examined the long-term effects of the sling on bladder function in a recently validated rat model of vaginal sling. MATERIALS AND METHODS: Stress urinary incontinence was created in 60 female Sprague-Dawley rats by the previously established method of bilateral pudendal nerve transection. Under anesthesia 20 animals received a vaginal sling, 20 received a vaginal sling in which the suburethral portion of the sling was cut immediately after placement and 20 received a sham vaginal sling. Six weeks after the procedures leak point pressure was determined and a cystometrogram was done using anesthesia in each animal via a previously implanted suprapubic catheter. Kruskal-Wallis and pairwise separate rank multiple comparison tests were performed with a significance level of 0.05. RESULTS: The cut and intact slings increased leak point pressure similarly and these values were significantly higher than that of the sham sling (24.9 and 27.9 cm H2O, respectively, vs 20.7, p <0.0001). Peak micturition pressure was not significantly different among the 3 groups, indicating absent bladder outlet obstruction in the sling groups. Bladder compliance was significantly decreased 6 weeks after placement of a cut or intact sling compared with the sham sling (p = 0.007 and 0.05, respectively). CONCLUSIONS: An intact suburethral portion is not a requirement for sling effectiveness in the rat model of stress urinary incontinence. However, the sling procedure decreases bladder compliance. This may explain the observed voiding dysfunction associated with sling procedures.     

Basic science and translational research in female pelvic floor disorders: proceedings of an NIH-sponsored meeting

AIMS: To report the findings of a multidisciplinary group of scientists focusing on issues in basic science and translational research related to female pelvic floor disorders, and to produce recommendations for a research agenda for investigators studying female pelvic floor disorders. METHODS: A National Institutes of Health (NIH)-sponsored meeting was held on November 14-15, 2002, bringing together scientists in diverse fields including obstetrics, gynecology, urogynecology, urology, gastroenterology, biomechanical engineering, neuroscience, endocrinology, and molecular biology. Recent and ongoing studies were presented and discussed, key gaps in knowledge were identified, and recommendations were made for research that would have the highest impact in making advances in the field of female pelvic floor disorders. RESULTS: The meeting included presentations and discussion on the use of animal models to better understand physiology and pathophysiology; neuromuscular injury (such as at childbirth) as a possible pathogenetic factor and mechanisms for recovery of function after injury; the use of biomechanical concepts and imaging to better understand the relationship between structure and function; and molecular and biochemical mechanisms that may underlie the development of female pelvic floor disorders. CONCLUSIONS: While the findings of current research will help elucidate the pathophysiologic pathways leading to the development of female pelvic floor disorders, much more research is needed for full understanding that will result in better care for patients through specific rather than empiric therapy, and lead to the potential for prevention on primary and secondary levels.     

Use of a human-derived liver cell line for the detection of cytoprotective, antigenotoxic and cogenotoxic agents

In this paper, we reviewed the data on the use of HepG2 cells to detect cytoprotective, antigenotoxic and cogenotoxic agents. Owing to their intact and inducible phase I and phase II enzymes, HepG2 cells are able to activate and detoxify xenobiotics and therefore reflect the metabolism of xenobiotics in the human body better than other metabolically incompetent cells used in conventional in vitro assays. Several dietary and non-dietary agents were found to be protective against different groups of cytotoxic and DNA-damaging xenobiotics in HepG2 cells and the mechanism of protection includes scavenging of electrophiles, reactive oxygen species and peroxides, inhibition of phase I activating enzymes, induction of phase II detoxifying enzymes and interactions with DNA-repair and/or replication processes. Additionally, certain non-mutagenic substances were found to enhance the effect of genotoxic agents in HepG2 cells by increasing the metabolic activation of the latter. In conclusion, HepG2 cells are of great relevance to detect cytotoxic and genotoxic substances and by extension cytoprotective, antigenotoxic and cogenotoxic agents.     

Evidence-based multidisciplinary practice: improving the safety and standards of male bladder catheterization.

A series of nursing care variances related to the procedure of catheterizing male patients stimulated an evidence-based practice project designed to define best practice for the technique of inserting male catheters. Results indicate current nursing knowledge may be inadequate.     

Recovery of Continence Function following Simulated Birth Trauma Involves Repair of Muscle and Nerves in the Urethra in the Female Mouse

Background

The natural history and the mechanisms behind the alteration of vaginal distension (VD) in a mouse model are not clear.

Objective

We examined the temporal sequelae of VD and pudendal nerve transection (PNT) on leak-point pressure (LPP) and the muscular and nerve components of the urethra in mice.

Design, setting, and participants

Seventy-two virgin female C57BL/6 mice were equally distributed into three groups. The VD group underwent VD for 1 h. The PNT group received bilateral PNT. A control group underwent sham VD.

Intervention

Each group was divided into four subgroups of six mice for measurement of LPP at 0, 4, 10, and 20 d after VD or PNT.

Measurements

LPP was measured. Morphology and neurofilament-immunoreactive nerve of the urethra were assessed.

Results and limitations

LPP was decreased at 0, 4, and 10 d but not at 20 d after VD. Decreased LPP persisted to 20 d in the PNT group. The external urethral striated muscle appeared disrupted and/or wavy in two mice at 0 d, in three mice at 4 d, in one mouse at 10 d, and in one mouse in 20 d after VD. The density of neurofilament-immunoreactive nerve in the urethra was reduced at 4 and 10 d after VD, but not at 20 d, and at 4, 10, and 20 d after PNT compared with the corresponding values of the sham VD group. The limitation of this animal model is that the pelvic floor structure of the mouse is different from that of female humans. Therefore, results of this study should be carefully applied to human subjects.

Conclusions

VD causes reversible stress urinary incontinence in female mice. Recovery of continence function following VD is associated with repair of the external urethral sphincter and reinnervation of the urethra. This mouse model will be useful for mechanistic investigation and targeting of therapeutic intervention by taking advantage of genetic manipulation.