Distribution and sub-types of afferent fibre in the mouse urinary bladder.

AIM: Increased afferent fibre activity contributes to pathological conditions such as the overactive bladder syndrome. Nerve fibres running near the urothelium are considered to be afferent as no efferent system has yet been described. The aim of this study was to identify sub-types of afferent nerve fibres in the mouse bladder wall based on morphological criteria and analyse regional differences. MATERIALS AND METHODS: 27 bladders of six month old C57BL/6 mice were removed and tissues were processed for immunohistochemistry. Cryostat sections were cut and stained for Protein Gene Product 9.5 (PGP), calcitonin gene related polypeptide (CGRP), neurofilament (NF), vesicular acetylcholine transporter (VAChT) and neuronal nitric oxide synthase (nNOS). RESULTS: In the sub-urothelium, different types of afferent nerve fibre were found, i.e. immunoreactive (IR) to; CGRP, NF, VAChT, and/or nNOS. At the bladder base, the sub-urothelium was more densely innervated by CGRP-IR and VAChT-IR nerve fibres, then at the lateral wall. NF- and nNOS nerves were sparsely distributed in the sub-urothelium throughout the bladder. At the lateral wall the inner muscle is densely innervated by CGRP-IR nerve fibres. NF, VAChT and nNOS nerves were evenly distributed in the different muscle layers throughout the bladder. Nerve fibre terminals expressing CGRP and NF were found within the extra-mural ganglia at the bladder base. CONCLUSIONS: Different types of afferent nerve fibres were identified in the sub-urothelium of the mouse bladder. At the bladder base the sub-urothelium is more densely innervated than the lateral wall by CGRP-IR and VAChT-IR afferent nerve fibres. CGRP and NF afferent nerve fibres in the muscle layer probably relay afferent input to external ganglia located near the bladder base. The identification of different afferent nerves in the sub-urothelium suggests a functional heterogeneity of the afferent nerve fibres in the urinary bladder.

Changes in voiding behavior in a mouse model of Alzheimer's disease.

Besides cognitive decline and behavioral alteration, urinary incontinence often occurs in patients suffering from Alzheimer's disease (AD). To determine whether the transgenic mouse model of AD, APP/PS1 (APP(SL)/PS1(M146L)) mouse, shows alteration of the urinary bladder function and anxiety, as for patients with AD, we examined the urinary marking behavior in relation to affective behavior. At 18 months of age voiding behavior of APP/PS1 and wild type (WT) mice was assessed by using a modified filter paper assay in combination with video tracing, with the cage divided into a center and corner zones. Anxiety-related behavior and locomotion were respectively tested in an elevated zero maze (EZM) and an open field (OF). The APP/PS1 mice urinated more in the center zone than the WT mice. The total volume of markings was significantly lower in the APP/PS1 mice. In both groups, the average volume of a marking in the corner zone was larger than in the center zone. In the EZM, the APP/PS1 mice spent less time in the open arms of the arena, considered as anxiogenic zones, than the WT mice. During the OF task, the APP/PS1 mice covered a longer distance than the WT mice. These findings show that the APP/PS1 mice have a different voiding behavior compared to the WT mice, i.e., urinating with small volumes and voiding in the center of the cage, and suggest that increased locomotor activity and anxiety-related behaviors are factors in the change in voiding pattern in the APP/PS1 mouse.

Robotic extravesical anti-reflux operations in complex cases: technical considerations and preliminary results.

OBJECTIVES: To evaluate technical aspects and outcome of robotic laparoscopic extravesical anti-reflux surgery in the treatment of high-grade vesicoureteral reflux (VUR) with associated complicating conditions. MATERIALS AND METHODS: Retrospective database and chart reviews were performed to identify a subgroup of patients with high-grade VUR who underwent robot-assisted anti-reflux surgery using the extravesical Lich-Gregoir repair and who additionally had preoperatively known complicating factors. Five such patients were operated on from 2005 to 2009. All had bilateral VUR, bladder dysfunction, breakthrough infections, renal scarring or at least one of the following complicating factors: posterior urethral valve bladders, duplex systems or para-ostial diverticula. Outcome and surgical aspects were assessed. RESULTS: At follow-up 9 of 10 ureters were free of reflux and diverticulae had disappeared completely. No lasting urinary retentions occurred but two boys needed reinsertion of a catheter for 24 h after surgery. No further complications were noted. There were no signs of obstruction, infections did not persist and there was no negative effect on bladder function. Dissection of para-ostial diverticula seemed the only additional technical challenge. CONCLUSIONS: Robot-assisted extravesical anti-reflux surgery seems a promising technique in the operative management of this unfavorable subset of patients. Reflux cure rate is higher than expected using injection therapy and at the same time morbidity seems lower than with open surgery. Further experience is needed to confirm these first impressions.

Changes in bladder innervation in a mouse model of Alzheimer's disease.

AIM: The aims of this study were to compare the structure of bladders from a transgenic mouse model of Alzheimer's disease with age matched control animals and to explore the idea that any structural differences might be related to functional bladder changes associated with the condition. MATERIALS AND METHODS: Two groups of mice were used. Transgenic animals in which the murine Amyloid Precursor Protein (APP) gene has been partly replaced by the human APP including both the Swedish and London mutations and that overexpress a mutant of the human Presenilin 1 gene (PS1M146L) driven by the PDGF promoter. The transgenic mice (App(SL)/PS1(M146L)) aged 24+/-3 months were used. The second group was an age matched control group of C57 black mice. The bladders from each group were isolated, fixed in 4% paraformaldehyde and prepared for immunohistochemistry. Antibodies to the vesicular acetylcholine transporter (VAChT) and neuronal nitric oxide synthase (nNOS) were used to identify neural structures. RESULTS: Cholinergic nerves (VAChT(+)) were observed in the inner and outer muscle bundles of App(SL)/PS1(M146L) and control mice. No major differences were noted in the distribution of these fibres. In contrast, there was a distinct difference in the innervation of the sub-urothelial layer. In App1(SL)/PS1(M146L) mice there were numerous VAChT and nNOS positive fibres in sharp contrast to the paucity of similar nerves in control animals. VAChT and nNOS did not appear to co-localise in the same nerve fibres within the lamina propria. Pairs of nerve fibres, nNOS(+) and VAChT(+), were observed to be intertwined and run in close proximity. A particularly unusual feature of the App(SL)/PS1(M146L) mouse bladder was the presence of neurones within the bladder wall. These nerve cell bodies were seen in all App(SL)/PS1(M146L) mouse bladders. The neurones could be found singly or in small ganglion like groups of cells and were located in all layers of the bladder wall (sub-urothelium, in the lamina propria adjacent to the inner muscle and within the inner muscle and outer muscle layers). No nerve cells or small ganglia were noted in any of the control bladders studied. CONCLUSIONS: There are structural differences in the bladders of App(SL)/PS1(M146L) mice compared to control animals. These differences are associated with sub-urothelial nerves which, because of their location, are likely to be sensory fibres. This may lead to a changed sensory processing from the App(SL)/PS1(M146L) bladders. The physiological role of the intra-mural neurones and ganglia is not known. It is speculated that they may be associated with peripheral motor/sensory mechanisms linked to the generation and modulation of sensation.

Effects of intranasal corticosteroid on nasal adenosine monophosphate challenge in persistent allergic rhinitis.

BACKGROUND: Response to a single dose nasal adenosine monophosphate challenge has been used as a surrogate inflammatory marker for allergic rhinitis. Attenuation of response following intranasal corticosteroid would further validate the challenge. OBJECTIVE: To assess the effect of 4 weeks of 200 mcg once daily mometasone furoate nasal spray on a simplified (single 160 mg dose) nasal adenosine monophosphate challenge. METHODS: Twenty participants with persistent allergic rhinitis completed a double blind placebo-controlled crossover study. Outcome measures were the peak nasal inspiratory flow and total nasal symptoms score responses to nasal adenosine monophosphate challenge, as well as domiciliary peak nasal inspiratory flow and patient symptom diary cards. RESULTS: Mometasone significantly (P < 0.05) attenuated response time profiles vs. placebo for peak nasal inspiratory flow but not total nasal symptom scores. For the maximum percentage fall this amounted to a mean difference of 9.6% (95% confidence interval 1.3-17.9%). The coefficient of variation for repeatability was 48.7%. Improvements were seen in prechallenge and domiciliary measurements of peak nasal inspiratory flow (both P < 0.05) and total nasal symptom scores (both P < 0.01). CONCLUSIONS: Mometasone attenuates the peak nasal inspiratory flow response to a single 160 mg nasal adenosine monophosphate challenge. Such challenges have been shown to be sensitive to the effects of antihistamines, antileukotrienes and now nasal steroids. This further supports their application as surrogate inflammatory markers for therapeutic trials in allergic rhinitis, potentially as 20 min challenges which can be conducted in a non-hospital setting.