ObjectiveTo investigate transient receptor potential vanilloid 4 (TRPV4) expression in bladder afferents and study the effect of TRPV4 and TRPV1 antagonists, alone and in combination, in bladder hyperactivity and pain induced by cystitis.
Material and MethodsTRPV4 expression in bladder afferents was analysed by immunohistochemistry in L6 dorsal root ganglia (DRG), labelled by fluorogold injected in the urinary bladder. TRPV4 and TRPV1 co-expression was also investigated in L6 DRG neurones of control rats and in rats with lipopolysaccharide (LPS)-induced cystitis. The effect of TRPV4 antagonist RN1734 and TRPV1 antagonist SB366791 on bladder hyperactivity and pain induced by cystitis was assessed by cystometry and visceral pain behaviour tests, respectively.
ResultsTRPV4 is expressed in sensory neurones that innervate the urinary bladder. TRPV4-positive bladder afferents represent a different population than the TRPV1-expressing bladder afferents, as their co-localisation was minimal in control and inflamed rats. While low doses of RN1734 and SB366791 (176.7 ng/kg and 143.9 ng/kg, respectively) had no effect on bladder activity, the co-administration of the two totally reversed bladder hyperactivity induced by LPS. In these same doses, the antagonists partially reversed bladder pain behaviour induced by cystitis.
ConclusionsTRPV4 and TRPV1 are present in different bladder afferent populations. The synergistic activity of antagonists for these receptors in very low doses may offer the opportunity to treat lower urinary tract symptoms while minimising the potential side-effects of each drug.
Aims: To determine whether glycosaminoglycan (GAG) replenishment is able to improve recovery of a deficient urothelial barrier, chondroitin sulfate (CS) instillations were tested using an in vitro model. Porcine urothelial cells (Ucells) were terminally differentiated in culture conditions to construct a urothelial layer with a functional barrier. This layer was damaged to compromise barrier function to simulate a key characteristic of bladder pain syndrome/interstitial cystitis. The functional effect of subsequent treatment with CS was evaluated.Methods: Primary porcine Ucells were isolated and cultured on inserts. Differentiation of cells was evaluated with immunohistochemical analysis for the presence of umbrella cells, tight junctions and CS. Transepithelial electrical resistance (TEER) measurements were performed to evaluate barrier function. Protamine was used to simulate mild urothelial damage. CS 0.2% (vol/vol), a GAG, was subsequently instilled in the treatment group. The recovery of barrier function was further evaluated with TEER measurements. The Student t test was used for the analysis of results.
The perioperative management of patients with hypokalemic familial periodic paralysis is well known and has been described previously. This disease does not preclude surgery as long as the surgical team is aware of the diagnosis preoperatively. We describe herein a patient with familial periodic paralysis diagnosed the first time 1 day after undergoing surgery.
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