Analysis of Expression of Acetylcholine and Acetylcholinesterase in the Urinary Bladder in Vesicoureteral Reflux in Children
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Numerous disorders of the lower urinary tract observed in children, such as dysfunctional voiding, infections or vesicoureteral reflux, may be caused by defective synchronization between the central nervous system and the activity of the lower urinary tract. The analysis of acetylcholine and acetylcholinesterase's activity - the mediator and inhibitor of neurotransmission in the parasympathetic nervous system - can provide a lot of information concerning the extent to which the anomalies have developed and the possibility of pharmacological correction of the aforementioned lower urinary tract pathology.The aim of the study was to determine the role of the parasympathetic nervous system in the pathological creation of vesicoureteral reflux.Material and methods. This study was conducted between the years 2000 and 2004 in the Clinic of Pediatric Surgery and Urology of Wrocław Medical University. Thirty children who underwent surgical correction of vesicoureteral reflux underwent full-thickness biopsy of the bladder wall during the procedure. In each case, the biopsy was taken from the top of the bladder incision used to perform uretrocy-stoneostomy; those children formed group "0". Nineteen children with neurogenic dysfunction of the lower urinary tract who had bladder-augmenting surgery also underwent biopsy from the top of the bladder incision; those children formed group "N". Results of the bladder wall's tests of 6 children who have undergone surgery to open the bladder for a different reason than vesicoureteral reflux were also analyzed (control group - K). The biopsies of the bladder wall were put on ice and immediately sent to the Immunohistochemy Laboratory of the Pathological Anatomy Institute of the Medical University in Wrocław. These samples underwent a reaction with monoclonal antybodies against acetylcholine and acetylcholinesterase to determine acetylcholine and acetylcholinesterase activity. Because of considerable difficulty in objective determination of the intensity of the colour reaction, an arbitrary division into three structural areas of the bladder was introduced:- epithelium- blood vessel endothelium- muscle layerIn order to interpret the results of the tests, a statistical analysis was performed.Results. Statistical analysis of the results shows a strong correlation between the occurrence of bladder instability and ACH stimulation in the bladder wall's muscle layer, both in children with vesicoureteral reflux and with neurogenic dysfunction of the lower urinary tract. A similar reaction occurs with ACHE and bladder instability. Degrees of this correlation suggest a strong cause-and-effect relationship between parasympathetic activity and the bladder instability phenomenon. One could ask at this point if it is caused by too much ACH or not enough ACHE activity. The performed analyses indicate that both processes are present.Conclusion. One of the preconditions of vesicoureteral reflux occurrence is excessive stimulation of the parasympathetic nervous system in bladder wall epithelium.
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- Sillen U: Vesicoureteral reflux in infants. Pediatr Nephrol 1999; 13: 355-61.
- Moncada S, Palmer RM, Higgis EA: Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 1991; 43: 109-42.
- Anderson KE, Hedlund P: Farmakologiczne aspekty fizjologii dolnych dróg moczowych. Urology (wydanie polskie) 2003; 1(1): 39-48.
- Anderson KE: Pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol Rev 1993; 45: 253-308.
- Anderson KE: Treatment of the overactive bladder: possible central nervous system drug targets. Urology 2002, 59(suppl.5A) 18-24.
- Apoznański W, Chrzan R: Ocena przydatności klinicznej badań przepływów cewkowych u dzieci w schorzeniach układu moczowego. Adv Clin Exp Med 2002; 11(1): 45-49.
- Groat de WC, Yoshimura N: Pharmacology of the lower urinary tract. Ann Rev Pharmacol Toxicol 2001; 41: 691-722.
- Arant BS Jr: Medical management of mild and moderate vesicoureteral reflux: Follow up studies of infants and young children. A preliminary report of the Southwest Pediatric Nephrology Group. J Urol 1992; 148: 1683-87.
- Bloom DA, Seeley WW, Ritchey ML et al.: Toilet habits and continence in children: an opportunity sampling in search of normal parameters. J Urol 1993; 149(5): 1087-90.
- Chen CC, Akopian AN, Sivilotti L: A P2X purinoceptor expressed by a subset of sensory neurons. Nature 1995; 377: 428-31.
- Amark P, Bussman G, Eksborg S: Follow up of long time treatment with intravesical oxybutynin for neurogenic bladder in children. Eur Urol 1998; 34: 148-53.
- Choppin A, Eglen RM, Hegde SS: Pharmacological characterization of muscarinic receptors in rabbit isolated iris sphincter muscle and urinary bladder smooth muscle. Br J Pharmacol 1998; 124: 883-88.
- An JY, Yun HS, Lee YP et al.: The intracellular pathway of the acetylocholine-induced contraction in cat detrusor muscle cells. Br J Pharmacol 2002; 137: 1001-10.
- Choppin A: Muscarinic receptors in isolated urinary bladder smooth muscle from different mouse strains. Br J Pharmacol 2002; 137: 522-28.
- Apoznański W, Chrzan R, Patkowski D i wsp.: Czynność dolnych dróg moczowych u dzieci z zakażeniami układu moczowego. Pol Merk Lek 2002; XII, 70: 279-82.
- Churchill BM, Aliabadi H, Landau EH: Ureteral bladder augmentation. J Urol 1993; 150: 716-20.
- Churchill BM, Jayanthi VR, Mc Lorie EH: Ureterocystoplasty importance of the proximal blood supply. J Urol 1995; 154: 197-98.
- Dacher JN, Savoye-Collet C: Urinary tract infection and functional bladder sphincter disorders in children. Eur Radiol 2004; 14: 101-06.
- Yiangou Y, Facer P, Ford A: Capsaicin receptor VR1 and ATP-gated ion channel P2X3 in human urinary bladder. BJU Int 2001; 87: 774-79.
- Elneil S, Skepper JN, Kidd EJ: Distribution of P2X(1) and P2X(3) receptors in the rat and human urinary bladder. Pharmacol 2001; 63: 120-28.
- Choppin A, Eglen RM: Pharmacological characterization of muscarinic in mouse isolated urinary bladder smooth muscle. Br J Pharmacol 2001; 133: 1035-40.
- Hjalmas K, Hoebeke PB, de Paepe H: Lower urinary tract dysfunction and urodynamics in children. Eur Urol 2000; 38/5 (Curric Urol 1.5, 1-11).
- Adams MC, Mitchell ME, Rink RC: Gastrocystoplasty: An alternative solution to the problem of urological reconstruction in the severely compromised patient. J Urol 1998: 140; 1152-57.
- Koff SA: Relationship between dysfunctional voinding and reflux. J Urol 1992; 148: 1703-07.
- Anderson KE: Bladder activation: afferent mechanisms. Urology 2002; 59(Suppl. 5A): 43-50.
- Nijman RJM: Neurogenic and non-neurogenic bladder dysfunction. Curr Opin In Urol 2001; 11: 577-83.
- Cockayne DA, Hamilton SG, Zhu QM: Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature 2000; 407: 1011-15.
- Nijman RJ: Classification and treatment of functional incontinence in children. BJU Int 2000; 85(Suppl 3): 37-42.
- Reitz A, Knapp PA, Muntener M et al.: Oral nitric oxide donors: a new pharmacological approach to detrusor-sphincter dyssynergia in spinal cord injured patients. Eur Urol 2004; 45: 516-20.
- Choppin A, Eglen RM: Pharmacological characterysation of muscarinic receptors in dog isolated ciliary and urinary bladder smooth muscle. Br J Pharmacol 2001; 132: 835-42.
- Baskin LS, Kogan BA, Benard F: Treatment of infants with neurogenic bladder dysfunction using anticholinergic drugs and intermittent catheterization. Br J Urol 1990; 161: 929-32.
- Agarwal SK, Khoury AE, Abramson RP et al.: Outcome analisis of vesicoureteral reflux in children with myelodysplasia. J Urol 1997; 157: 980-82.[WoS]
- Smellie JM: The intravenous urogram in the detection and evaluation of renal damage following urinary tract infection. Pediatr Nephrol 1995; 9: 213-19.
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