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Videocystometry, combining x-ray and cystometry, provides unprecedented details on urinary tract function in rodents., Lower urinary tract dysfunction (LUTd) represents a major health care problem with a high, unmet medical need. Design of additional therapies for LUTd requires precise tools to study bladder storage and voiding (dys)function in animal models. We developed videocystometry in mice, combining intravesical pressure measurements with high-speed fluoroscopy of the urinary tract. Videocystometry substantially outperforms current state-of-the-art methods to monitor the urine storage and voiding process, by enabling quantitative analysis of voiding efficiency, urethral flow, vesicoureteral reflux, and the relation between intravesical pressure and flow, in both anesthetized and awake, nonrestrained mice. Using videocystometry, we identified localized bladder wall micromotions correlated with different states of the filling/voiding cycle, revealed an acute effect of TRPV1 channel activation on voiding efficiency, and pinpointed the effects of urethane anesthesia on urine storage and urethral flow. Videocystometry has broad applications, ranging from the elucidation of molecular mechanisms of bladder control to drug development for LUTd.

BACKGROUND: Improvement of bladder emptying by modulating afferent nerve activity is an attractive therapeutic strategy for detrusor underactivity. Transient receptor potential vanilloid 4 (TRPV4) is a sensory ion channel in urothelial cells that contribute to the detection of bladder filling. OBJECTIVE: To investigate the potential benefit of intravesical TRPV4 agonists in a pelvic nerve injury rat model for detrusor underactivity. DESIGN, SETTING, AND PARTICIPANTS: Female wild-type and Trpv4 knockout rats underwent sham surgery or bilateral pelvic nerve injury (bPNI). Four weeks later, rats underwent cystometry with infusion of the TRPV4 agonist GSK1016790A. Bladders were harvested for in vitro pharmacological studies, quantitative reverse polymerase chain reaction and immunohistochemistry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data are expressed as median ± interquartile range. Statistical comparisons were made using the Mann-Witney U test and Wilcoxon signed rank test as appropriate. RESULTS AND LIMITATIONS: Rats with bPNI showed a phenotype characteristic of detrusor underactivity with lower-amplitude voiding contractions, decreased voiding frequency, and increased postvoid residual. Intravesical application of GSK1016790A increased voiding frequency and reduced postvoid residual in wild-type, but not Trpv4-/-, rats. In isolated bladder strips, GSK1016790A did not induce relevant contractions, indicating that the observed improvements in bladder function are the result of increased afferent signalling through TRPV4 activation, rather than a local effect on the detrusor. The altered urinary phenotype of Trpv4-/- mice was not apparent in the Trpv4-/- rat model, suggesting species-related functional variations. Our results are limited to the preclinical setting in rodents. CONCLUSIONS: Intravesical activation of TRPV4 improves bladder dysfunction after bPNI by increasing afferent signalling. PATIENT SUMMARY: We demonstrate that the sensory protein transient receptor potential vanilloid 4 (TRPV4) can be targeted to improve bladder function in animals that have iatrogenic injury to the nerves innervating the bladder. Further research is required to determine whether these results can be translated to patients with an underactive bladder. ispartof: EUROPEAN UROLOGY vol:74 issue:3 pages:336-345 ispartof: location:Switzerland status: published

Lower urinary tract dysfunction (LUTd) represents a major healthcare problem. Although it is mostly not lethal, associated social disturbance, medical costs, loss of productivity and especially diminished quality of life should not be underestimated. Although more than 15% of people suffer from a form of LUTd to some extent, pathophysiology often remains obscure. In the past 20 years, transient receptor potential (TRP) channels have become increasingly important in this field of research. These intriguing ion channels are believed to be the main molecular sensors that generate bladder sensation. Therefore, they are intensely pursued as new drug targets for both curative and symptomatic treatment of different forms of LUTd. TRPV1 was the first of its class to be investigated. Actually, even before this channel was cloned, it had already been targeted in the bladder, with clinical trials of intravesical capsaicin instillations. Several other polymodally gated TRP channels, particularly TRPM8, TRPA1 and TRPV4, also appear to play a prominent role in bladder (patho)physiology. With this review, we provide a brief overview of current knowledge on the role of these TRP channels in LUTd and their potential as molecular targets for treatment.

The interest in using Jatropha curcas L. (JCL) as a feedstock for the production of bio-diesel is rapidly growing. The properties of the crop and its oil have persuaded investors, policy makers and clean development mechanism (CDM) project developers to consider JCL as a substitute for fossil fuels to reduce greenhouse gas emissions. However, JCL is still a wild plant of which basic agronomic properties are not thoroughly understood and the environmental effects have not been investigated yet. Gray literature reports are very optimistic on simultaneous wasteland reclamation capability and oil yields, further fueling the Jatropha bio-diesel hype. In this paper, we give an overview of the currently available information on the different process steps of the production process of bio-diesel from JCL, being cultivation and production of seeds, extraction of the oil, conversion to and the use of the bio-diesel and the by-products. Based on this collection of data and information the best available practice, the shortcomings and the potential environmental risks and benefits are discussed for each production step. The review concludes with a call for general precaution and for science to be applied. ispartof: Biomass & Bioenergy vol:32 issue:12 pages:1063-1084 status: published

BACKGROUND: Acute exposure of part of the skin to cold stimuli can evoke urinary urgency, a phenomenon termed acute cold-induced urgency (ACIU). Despite its high prevalence, particularly in patients with overactive bladder, little is known about the mechanisms that induce ACIU. OBJECTIVE: To develop an animal model of ACIU and test the involvement of cold-activated ion channels transient receptor potential (TRP) M8 and TRPA1. DESIGN, SETTING, AND PARTICIPANTS: Intravesical pressure and micturition were monitored in female mice (wild-type C57BL/6J, Trpa1(-/-), Trpm8(+/+), and Trpm8(-/-)) and Sprague Dawley rats. INTERVENTIONS: An intravesical catheter was implanted. Localized cooling of the skin was achieved using a stream of air or topical acetone. The TRPM8 antagonist (N-(3-aminopropyl)-2-{[(3-methylphenyl) methyl]oxy}-N-(2-thienylmethyl)benzamide (AMTB) or vehicle was injected intraperitoneally. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Frequencies of bladder contractions and voids in response to sensory stimuli were compared using the Mann-Whitney or Kruskal-Wallis test. RESULTS AND LIMITATIONS: Brief, innocuously cold stimuli applied to different parts of the skin evoked rapid bladder contractions and voids in anesthetized mice and rats. These responses were strongly attenuated in Trpm8(-/-) mice and in rats treated with AMTB. As rodent bladder physiology differs from that of humans, it is difficult to directly extrapolate our findings to human patients. CONCLUSIONS: Our findings indicate that ACIU is an evolutionarily conserved reflex rather than subconscious conditioning, and provide a useful in vivo model for further investigation of the underlying mechanisms. Pharmacological inhibition of TRPM8 may be useful for treating ACIU symptoms in patients. PATIENT SUMMARY: Brief cold stimuli applied to the skin can evoke a sudden desire to urinate, which can be highly bothersome in patients with overactive bladder. We developed an animal model to study this phenomenon, and found that it depends on a specific molecular cold sensor, transient receptor potential M8 (TRPM8). Pharmacological inhibition of TRPM8 may alleviate acute cold-induced urinary urgency in humans. publisher: Elsevier articletitle: Essential Role of Transient Receptor Potential M8 (TRPM8) in a Model of Acute Cold-induced Urinary Urgency journaltitle: European Urology articlelink: http://dx.doi.org/10.1016/j.eururo.2015.03.037 content_type: article copyright: Copyright © 2015 European Association of Urology. Published by Elsevier B.V. ispartof: European Urology vol:68 issue:4 pages:655-661 ispartof: location:Madrid status: published

Background This feasibility study established an experimental protocol to evaluate brain activation patterns using fluorodeoxyglucose positron emission tomography ((18F)FDG-PET) during volume-induced voiding and isovolumetric bladder contractions in rats. Methods Female Sprague-Dawley rats were anaesthetized with urethane and underwent either volume-induced voiding cystometry or isovolumetric cystometry and simultaneous functional PET brain imaging after injection of (18F)FDG in the tail vein. Brain glucose metabolism in both groups was compared to their respective control conditions (empty bladder). Relative glucose metabolism images were anatomically standardized to Paxinos space and analysed voxel-wise using Statistical Parametric Mapping 12 (SPM12). Results During volume-induced voiding, glucose hypermetabolism was observed in the insular cortex while uptake was decreased in a cerebellar cluster and the dorsal midbrain. Relative glucose metabolism during isovolumetric bladder contractions increased in the insular and cingulate cortices and decreased in the cerebellum. Conclusions Our findings demonstrate that volume-induced voiding as well as isovolumetric bladder contractions in rats provokes changes in brain metabolism, including activation of the insular and cingulate cortices, which is consistent with their role in the mapping of bladder afferent activity. These findings are in line with human studies. Our results provide a basis for further research into the brain control of the lower urinary tract in small laboratory animals.