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  • Fraser, Matthew O., et al. (författare)
  • Best practices for cystometric evaluation of lower urinary tract function in muriform rodents
  • 2020
  • Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467 .- 1520-6777. ; 39:6, s. 1868-1884
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Rodent cystometry has provided valuable insights into the impact of the disease, injury, and aging on the cellular and molecular pathways, neurologic processes, and biomechanics of lower urinary tract function. The purpose of this white paper is to highlight the benefits and shortcomings of different experimental methods and strategies and to provide guidance on the proper interpretation of results. Methods: Literature search, selection of articles, and conclusions based on discussions among a panel of workers in the field. Results: A range of cystometric tests and techniques used to explore biological phenomena relevant to the lower urinary tract are described, the advantages and disadvantages of various experimental conditions are discussed, and guidance on the practical aspects of experimental execution and proper interpretation of results are provided. Conclusions: Cystometric evaluation of rodents comprises an extensive collection of functional tests that can be performed under a variety of experimental conditions. Decisions regarding which approaches to choose should be determined by the specific questions to be addressed and implementation of the test should follow standardized procedures.
  • Frederiksen, Hans, et al. (författare)
  • Nerve induced responses and force-velocity relations of regenerated detrusor muscle after subtotal cystectomy in the rat.
  • 2004
  • Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467 .- 1520-6777. ; 23:2, s. 159-165
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: To study the pharmacological and mechanical properties of newly developed detrusor muscle after subtotal cystectomy, to explore if the regenerated detrusor has characteristics similar to the normal bladder base, from which it regenerated, or to the normal bladder body which it replaces. METHODS: Partial cystectomy was performed in female rats. Fifteen weeks later, detrusor strips were cut from supratrigonal and equatorial segments. Unoperated rats served as controls. Responses to field stimulation were obtained in the absence and presence of scopolamine, prazosin, and P2X1 blockade. Dose-response curves were obtained for carbachol, alpha,beta-methylene-ATP, and phenylephrine. Force-velocity data were obtained on maximally activated chemically skinned preparations. RESULTS: Maximal contractile response to field stimulation was 60% of that to high-K+ with no difference between strips from control and cystectomy bladders. Prazosin had no effect. Scopolamine decreased maximal response of supratrigonal strips to 62 +/- 6 (controls) and 61 +/- 4% (operated) of that without blocker. For equatorial strips the decrease was to 81 +/- 5 (controls) and 58 +/- 8% (operated). Frequency-response relations were obtained during blockade with scopolamine, alpha,beta-methylene-ATP, and prazosin. Supratrigonal strips showed a pronounced additional inhibition up to 40 Hz. Equatorial strips from controls were completely inhibited at all frequencies. Equatorial strips from operated bladders were inhibited up to 20 Hz but not at 40 and 60 Hz. Carbachol EC(50) values were similar in all groups. Maximum response to phenylephrine was 10-20% of high-K+ response. Maximal shortening velocity (Vmax) was similar in control supratrigonal and equatorial strips, but was significantly lower in the operated bladders. CONCLUSIONS: (1): A regional difference exists in pharmacological properties of control detrusor, with a considerable contractile response to stimulation remaining in the supratrigonal muscle after simultaneous cholinergic, adrenergic, and purinergic blockade. (2): The new detrusor was functionally well innervated with no supersensitivity to muscarinic stimulation. (3): The newly formed bladder body had pharmacological properties specific for the supratrigonal segment from which it had developed. (4): There was no regional difference in force-velocity characteristics of the control detrusor. (5): The lowered Vmax in the newly formed bladder might thus be related to growth and regeneration of muscle cells.
  • Frederiksen, Hans, et al. (författare)
  • Regeneration of detrusor muscle after subtotal cystectomy in the rat; effects on contractile proteins and bladder mechanics.
  • 2001
  • Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467 .- 1520-6777. ; 20:6, s. 685-697
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the present study was to determine to what extent adult rats can produce new contracting bladder muscle and to see if such newly formed bladder tissue possesses characteristic mechanical properties or whether the ability to recover mechanically is so pronounced that the prehistory of the bladder is unimportant. Subtotal cystectomy was performed in adult female rats, leading to a pronounced decrease in total bladder weight. At 10 weeks, bladder weight had normalized. The histological appearance of such bladders was similar to that of the controls. Active and passive length-tension relations for the detrusor muscle were determined in controls and up to 10 weeks after surgery. Immediately after surgery active and passive forces showed a leftward shift and maximum active force decreased markedly. With time the length-tension curves shifted back to normal, but a decreased active force still remained at 10 weeks. Detrusor actin concentration and detrusor myosin/actin ratio were unaffected by the subtotal cystectomy. Intermediate filament protein/actin ratio showed a significant but transitory increase. We conclude that there is a remarkable recovery of detrusor muscle function after subtotal cystectomy, leading to a normalization of optimum length for active force and a net synthesis of contractile and cytoskeletal proteins. The ability to produce active force does, however, not fully recover.
  • Fry, Christopher Henry, et al. (författare)
  • New targets for overactive bladder—ICI-RS 2109
  • 2020
  • Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467 .- 1520-6777. ; 39:S3, s. 113-121
  • Forskningsöversikt (refereegranskat)abstract
    • Aim: To review evidence for novel drug targets that can manage overactive bladder (OAB) symptoms. Methods: A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterize their use to treat OAB. Results: Five classes of agents or cellular pathways were considered. (a) Cyclic nucleotide–dependent (cyclic adenosine monophosphate and cyclic guanosine monophosphate) pathways that modulate adenosine triphosphate release from motor nerves and urothelium. (b) Novel targets for β3 agonists, including the bladder wall vasculature and muscularis mucosa. (c) Several TRP channels (TRPV1, TRPV4, TRPA1, and TRPM4) and their modulators in affecting detrusor overactivity. (d) Small conductance Ca2+-activated K+ channels and their influence on spontaneous contractions. (e) Antifibrosis agents that act to modulate directly or indirectly the TGF-β pathway—the canonical fibrosis pathway. Conclusions: The specificity of action remains a consideration if particular classes of agents can be considered for future development as receptors or pathways that mediate actions of the above mentioned potential agents are distributed among most organ systems. The tasks are to determine more detail of the pathological changes that occur in the OAB and how the specificity of potential drugs may be directed to bladder pathological changes. An important conclusion was that the storage, not the voiding, phase in the micturition cycle should be investigated and potential targets lie in the whole range of tissue in the bladder wall and not just detrusor.
  • Fuellhase, Claudius, et al. (författare)
  • Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats
  • 2016
  • Ingår i: Neurourology and Urodynamics. - : WILEY-BLACKWELL. - 0733-2467 .- 1520-6777. ; 35:4, s. 464-470
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsTo test if urodynamic effects from systemic Fatty Acid Amide Hydrolase (FAAH) inhibition involve sacral spinal cannabinoid type 1 (CB1) or type 2 (CB2) receptors. MethodsMale rats with or without partial urethral obstruction were used for cystometry or immunohistochemistry. Urodynamic effects of intravenous (IV) 0.3mg/kg Oleoyl Ethyl Amide (OEtA; FAAH inhibitor), and intrathecal (IT) 5g rimonabant (CB1 antagonist) or 5g SR144528 (CB2 antagonist) were studied in awake rats. ResultsAfter administration of rimonabant or SR144528, non-obstructed rats with normal bladder function developed bladder overactivity (BO), which was counteracted by OEtA. OEtA also counteracted BO in obstructed rats. SR144528 did not affect bladder function in obstructed rats but counteracted the urodynamic effects of OEtA. Surprisingly, rimonabant (and AM251, another CB1 antagonist) reduced BO in obstructed rats, whereafter OEtA produced no additional urodynamic effects. CB1 expression increased in the sacral spinal cord of obstructed rats whereas no changes were observed for CB2 or FAAH. ConclusionsUrodynamic effects of systemic FAAH inhibition involve activities at spinal neuronal CB1 and CB2 receptors in normal and obstructed rats. Endogenous spinal CB receptor ligands seem to regulate normal micturition and BO. Altered spinal CB receptor functions may be involved in the pathogenesis of obstruction-induced BO. Neurourol. Urodynam. 35:464-470, 2016. (c) 2015 Wiley Periodicals, Inc.
  • Gandaglia, G., et al. (författare)
  • The fatty acid amide hydrolase inhibitor oleoyl ethyl amide counteracts bladder overactivity in female rats
  • 2014
  • Ingår i: Neurourology and Urodynamics. - : John Wiley & Sons. - 0733-2467 .- 1520-6777. ; 33:8, s. 1251-1258
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS:To study micturition and bladder overactivity in female rats after chronic treatment with the fatty acid amide hydrolase (FAAH) inhibitor oleoyl ethyl amide (OEtA).METHODS:Sprague-Dawley rats received daily subcutaneous injections of OEtA (0.3 mg/kg), or vehicle for 2 weeks. Cystometries, organ bath studies, Western blot, and immunofluorescence were then used. Expressions of FAAH, cannabinoid 1 and 2 receptors (CB1 and CB2), mitogen-activated protein kinase (MAPK), vesicular acetyl choline-transporter protein (VAChT), and calcitonin gene-related peptide (CGRP) were evaluated.RESULTS:At baseline, OEtA-treated rats had higher values (P < 0.05) of micturition intervals (MI) and volumes (MV), bladder capacity (BC), threshold pressure, and flow pressure than vehicle controls. Intravesical PGE2 reduced MI, MV, and BC, and increased basal pressure and the area under the curve in all rats. However, these urodynamic parameters were altered less by intravesical PGE2 in OEtA-treated rats (P < 0.05 vs. vehicle controls). Compared to vehicle controls, detrusor from OEtA-treated rats had larger contractions to carbachol at 10-0.1 µM, but no difference in Emax was recorded. FAAH, CB1, CB2, VAChT, or CGRP was similarly expressed in bladders from all rats. In separate experiments, intravesical OEtA increased mucosal expression of phosphorylated MAPK.CONCLUSIONS:Chronic FAAH inhibition altered sensory urodynamic parameters and reduced bladder overactivity. Even if it cannot be excluded that OEtA may act on central nervous sensory pathways to contribute to these effects, the presence of FAAH and CB receptors in the bladder and activation of intracellular signals for CB receptors by intravesical OEtA suggest a local role for FAAH in micturition control. Neurourol. Urodynam
  • Gladh, Gunilla, 1943- (författare)
  • Effect of thoughtful preparation on the catheterization of children undergoing investigative studies
  • 2003
  • Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467 .- 1520-6777. ; 22:1, s. 58-61
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims:To evaluate an anesthetic sedation free method of transurethral catheterization in children.Methods:The child and his or her parents are thoroughly prepared for the procedure by means of written and oral child-adapted information and practical instructions. To evaluate this routine, a simple questionnaire was given to 115 consecutive children undergoing transurethral catheterization.Results:The questionnaire was returned by 99 children (86%). Most children and parents (95) found the preparation“good”or“very good”and tolerated the catheterization procedure well. Only six children reported the catheterization to be“very painful”(without requiring that the procedure was terminated). Complications, such as urgency, smarting pain during voidings, or both, after withdrawal of the catheter, occurred in 12 children and urinary tract infections in 3. Unexpectedly, girls were affected more often than boys.Conclusions:Careful preparation of children and their parents allows the great majority of diagnostic studies that require urethral catheterization to be accomplished without anesthesia. Neurourol. Urodynam. 22:58–61, 2003. © 2003 Wiley-Liss, Inc.
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