Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria

Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (?10 wbc/?l) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation. Here, using bladder biopsy samples, we have investigated urothelial ATP signaling in OAB patients with microscopic pyuria. Basal, but not stretch-evoked, release of ATP was significantly greater from the urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc/?l). Basal ATP release from the urothelium of OAB patients with pyuria was inhibited by the P2 receptor antagonist suramin and abolished by the hemichannel blocker carbenoxolone, which differed from stretch-activated ATP release. Altered P2 receptor expression was evident in the urothelium from pyuric OAB patients. Furthermore, intracellular bacteria were visualized in shed urothelial cells from ?80% of OAB patients with pyuria. These data suggest that increased ATP release from the urothelium, involving bacterial colonization, may play a role in the heightened symptoms associated with pyuric OAB patients

Metateoretiese vertrekpunte ten opsigte van wetenskaplike navorsing in kinder- en jeugbediening

OPSOMING: Hierdie artikel vorm deel van ’n navorsingsprojek oor die verrekening van die metateoretiese vertrekpunte in die wetenskap van die Praktiese Teologie. Die eerste fase van die reeks bied die teoretiese onderbou vir die werklikheids-, hermeneutiese en wetenskapsteoretiese beskouing van die vak. Die tweede fase fokus op die invloed wat hierdie vertrekpunte op die wetenskaplike navorsing van die verskillende vakgroepe in die Praktiese Teologie het. Hierdie artikel handel oor die wetenskaplike benaderingswyse tot die navorsingsveld van Kinder- en jeugbediening. In hierdie navorsingsartikel word die persoonlike metateoretiese perspektief waarmee die vakgebied van Kinder- en jeugbediening benader word, uitgespel en verantwoord ten opsigte van die werklikheidsbeskouing waarmee daar op die navorsingsveld van Kinder- en jeugbediening gefokus word; die onderbou van die hermeneutiese beskouing wat nodig is om tot ’n verstaan en ’n verantwoordbare verhouding te kom tussen die elemente wat in Kinderen jeugbediening ter sprake is; en ten slotte, om die wetenskapsteoretiese benadering te beskryf waarmee die navorsingsveld van Kinder- en jeugbediening op ’n wetenskaplikverantwoorde wyse ondersoek kan word. ABSTRACT: Metatheoretical assumptions in scientific pastoral-theological research regarding child and youth ministry. This article is part of a research project on the metatheoretical assumptions in Practical Theology. The first part of this series gives the theoretical foundation for the view on reality-, hermeneutical- and scientific-theoretical approaches to the research field. The second part focuses on the effect that these assumptions will have on the scientific research of the various subject groups in Practical Theology. This article describes the scientific approach to the research field of child and youth ministry. This research article describes the personal metatheoretical perspective from which the subject area is approached, and it gives account of the view on reality with which the research field of Youth Ministry is studied; of the foundation on which the hermeneutical viewpoint is built, to attain an understanding and a founded relationship between the elements that are applicable in child and youth ministry; and finally, the scientific theoretical approach to the research field in a justified manner.http://www.inluceverbi.org.za/index.php/skriflighttp://dx.doi.org/10.4102/ids.v47i1.579http://www.indieskriflig.org.za/index.php/skriflig/article/view/57

Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria

Overactive Bladder (OAB) is an idiopathic condition, characterized by urgency, urinary frequency, and urgency incontinence, in the absence of routinely traceable urinary infection. We have described microscopic pyuria (≥10 wbc/μl) in patients suffering from the worst symptoms. It is established that inflammation is associated with increased ATP release from epithelial cells, and extracellular ATP originating from the urothelium following increased hydrostatic pressure is a mediator of bladder sensation. Here, using bladder biopsy samples, we have investigated urothelial ATP signaling in OAB patients with microscopic pyuria. Basal, but not stretch-evoked, release of ATP was significantly greater from the urothelium of OAB patients with pyuria than from non-OAB patients or OAB patients without pyuria (<10 wbc/μl). Basal ATP release from the urothelium of OAB patients with pyuria was inhibited by the P2 receptor antagonist suramin and abolished by the hemichannel blocker carbenoxolone, which differed from stretch-activated ATP release. Altered P2 receptor expression was evident in the urothelium from pyuric OAB patients. Furthermore, intracellular bacteria were visualized in shed urothelial cells from ∼80% of OAB patients with pyuria. These data suggest that increased ATP release from the urothelium, involving bacterial colonization, may play a role in the heightened symptoms associated with pyuric OAB patients