To investigate whether the expression of P2X3 receptors (implicated in the pathophysiology of pain) is altered in human bladder urothelium from patients with interstitial cystitis (IC, a major symptom of which is pain), and as P2X2 receptors can be co‐expressed with P2X3 receptors, to assess their expression also.
PATIENTS AND METHODS
Bladder tissue samples were collected from patients undergoing cystectomy or radical prostatectomy. Patients with IC were diagnosed using the international criteria. RNA protein expression levels of both receptors were evaluated using reverse transcription‐polymerase chain reaction (PCR), real‐time quantitative PCR and Western blot analysis.
P2X2 was expressed in the human urothelium, in a glycosylated form. There was less gene expression of P2X3 in IC urothelium, whereas P2X2 gene expression was unchanged. This contrasted with the protein expression, which was increased for both P2X2 and P2X3.
This is the first report of the expression of the P2X2 receptor in human bladder urothelium. There was greater protein expression of both P2X2 and P2X3 in IC bladder urothelium which did not directly correlate with the gene expression. Changes in expression of P2X2 and P2X3 receptors may contribute to the pain that patients with IC have, and might provide novel drug targets.
Complications of surgical mesh procedures have led to legal cases against manufacturers worldwide and to national inquiries about their safety. The aim of this study was to investigate the rate of adverse events of these procedures for stress urinary incontinence in England over 8 years. This was a retrospective cohort study of first-time tension-free vaginal tape (TVT), trans-obturator tape (TOT) or suprapubic sling (SS) surgical mesh procedures between April 2007 and March 2015. Cases were identified from the Hospital Episode Statistics database. Outcomes included number and type of procedures, including those potentially confounded by concomitant procedures, and frequency, nature and timing of complications. 92,246 first-time surgical mesh procedures (56,648 TVT, 34,704 TOT, 834 SS and 60 combinations) were identified, including 68,002 unconfounded procedures. Peri-procedural and 30-day complication rates in the unconfounded cohort were 2.4 [2.3–2.5]% and 1.7 [1.6–1.8]% respectively; 5.9 [5.7–6.1]% were readmitted at least once within 5 years for further mesh intervention or symptoms of complications, the highest risk being within the first 2 years. Complication rates were higher in the potentially confounded cohort. The complication rate within 5 years of the mesh procedure was 9.8 [9.6:10.0]% This evidence can inform future decision-making on this procedure.
Adenosine 5′-triphosphate (ATP) is known to play a significant role as a neurotransmitter in smooth muscle. There is evidence to show that ATP can cause bladder contractions and may also be involved in the processing of sensory information in the urinary bladder. These effects are likely to be mediated by P2X receptors, namely P2X1 and P2X3, respectively. This study set out to investigate their distribution in rat and human urinary bladders. P2X1 receptor immunoreactivity was found on detrusor muscle fibres and P2X3 receptor immunoreactivity was found in the urothelium of both species. This is the first demonstration of a non-neuronal localisation for P2X3 receptors. No clear evidence was found for the presence of P2X3 receptors on calcitonin gene-related peptide-containing sensory nerves and therefore P2X3 receptors may not have a direct role in the mediation of sensory responses to ATP in the urinary bladder.
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