Cellular and molecular mechanisms of obstruction induced bladder dysfunction.

• Grant number: 16/14146-5
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2017
• End date: January 31, 2019
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Cristiano Mendes Gomes
• Grantee: Cristiano Mendes Gomes
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Carlos Henrique Suzuki Bellucci ; Thiago Souto Hemerly

Abstract

The bladder outlet obstruction (BOO) is a common cause of urinary disorders in patients of all ages. Clinical manifestations associated with BOO has a wide spectrum of symptoms, reflecting the pathological responses of the bladder to obstruction. These answers depends on several factors such as the time of obstruction (during embryonic development, in childhood or adult), the duration of obstructive process (acute or chronic), type (constrictive or compression) and severity (partial or complete).Knowledge of the obstructive processes that results in BOO in humans and the study of animal models of BOO (used to assess the effects of BOO in bladder function) are important to understand the pathophysiological mechanisms of the BOO and the bladder consequences thereof.The identification of these aspects related to the BOO can contribute to the development of therapeutic methods that can minimize the consequences to the bladder, and create mechanisms to evaluate the potential recovery of bladder after removing the obstructive process.In adults, the leading cause of BOO is benign prostatic hyperplasia (BPH), one of the most frequent pathological conditions in men over the age of 50 whose prevalence increases progressively with age. It can have a major impact on health and quality of life of patients and constitutes the second largest indication for surgery in this population. Other common causes are bladder neck contracture, urethral stricture, prostate cancer and vesicoureteral sphincter of neurogenic cause.n response to the obstruction, bladder smooth muscle (detrusor) undergoes remodeling process that results in detrusor hypertrophy, necessary to offset the need for increased contractility to overcome the increase in urethral resistance during urination. With the persistence of obstructive process, the detrusor can go to a decompensation stage, resulting in permanent contraction of disability.Few studies in humans have been made regarding various aspects of physiology and morphology bladder are altered in animal models of BOO.Fifty patients will be included in the study, with indication of open surgery (transvesical prostatectomy ) for the treatment of benign prostatic hyperplasia and thirty patients with neurogenic bladder with bladder augmentation surgery indication.The transvesical prostatectomy and bladder augmentation will be performed classical and routinely by a surgical team of Urology Division of Hospital das Clinicas, Faculty of Medicine, University of São Paulo. A fragment bladder interesting all layers of the bladder wall and measuring 2.0 x 0.5 cm is obtained from one of the edges of the bladder incision immediately before starting the closure of the bladder.histochemical and immunohistochemical studies will be conducted to evaluate the collagen expression in detrusor smooth muscle ratio: extracellular matrix and ratio of the two most important types of collagen in the bladder (Type I: Type III); the expression of collagen types will also be assessed in m-RNA level by methods chain reaction reverse-transcriptase polymerase (RT-PCR) and agarose gel electrophoresis (SDS-PAGE). The dosage neuronal tissue growth factor is performed by immunohistochemistry (Promega Emax® NGF). The dosage of tissue hypoxia inducible factor by 1 ± will be performed by immunohistochemistry (monoclonal SIGMA Anti-HIF-1 ±). The study of the presence and quantification of interstitial cells of Cajal will be accomplished by immunohistochemical marker c-Kit.The observed cellular and molecular changes will be compared between groups in order to investigate their associations with the process of BOO changes in bladder compliance and the presence of detrusor overactivity. We will correlate such structural changes with the symptoms and urodynamic findings (AU)