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Diabetes Induced Changes in Rat Urinary Bladder and Urethral Epithelium
Summary Data Summary
Applicant Birder, Lori
E-Mail Address lbirder@pitt.edu
Project Title Diabetes Induced Changes in Rat Urinary Bladder and Urethral Epithelium
CBU ID 09MCG90
External SubContract ID 20497-33
Diabetic Complication Uropathy
Funding Program Group Pilot & Feasibility [PF2009]
Abstract Diabetic bladder dysfunction (DBD) is among the most common and incapacitating
complications of type I diabetes mellitus (DM), resulting in urinary
incontinence and poor emptying of the bladder, and affecting quality of life
substantially. Despite the prevalence of DBD, many details of the natural
history and mechanism of this condition remain unknown. Exploration of those
details in a series of laboratory experiments using streptozotocin (STZ)-induced
DM in rats has revealed that the bladder undergoes morphometric and functional
changes leading to altered voiding function. Recent evidence supports a sensory
role for the bladder uro-epithelium and suggests that these epithelial cells may
play a prominent role in voiding function in addition to their role as a
barrier. Moreover, the role of the urethra has recently been recognized, and
alterations in urethral function are also found in DM. Systemically, DM is
associated with various changes including plasma osmolarity, glucose levels, and
changes in autonomic and neuroendocrine function. These alterations could impact
the epithelial cells lining the bladder and urethra and ultimately changes in
their sensory function may adversely affect the underlying muscle and
innervation. Moreover, changes in epithelial barrier function and urine
constituency may be predisposing conditions for infectious/inflammatory
processes. In order to begin to explore the effect of DM on epithelial function,
we will compare morphological and immunohistochemical characteristics of
epithelial cells lining the lower urinary tract (LUT) in normal and STZ-treated
DM rats. We hypothesize that the DM-induced epithelial sensory dysfunction will
lead to changes in the ‘sensory-web’ directly and thereby result in LUT
dysfunction. A secondary effect on bladder function, that caused by altered
barrier function necessary during storage, may also be a feature of this disease
state. Defects in uro-epithelial sensor molecules and epithelial-signaling
(which could lead to activation of bladder afferents) are likely to contribute
to the pathogenesis of diabetic bladder dysfunction and impaired sensation. This
suggests that targeting urothelial cell sensor molecules and urothelial-cell
signaling may lead to novel therapeutic approaches in the treatment of diabetic
bladder.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 27796
Supply Total Costs 10000
Equipment Total Costs 0
Travel/Other Total Costs 16749
Direct Costs 54545
Indirect Costs Proposed 5454
Total Costs Proposed 59999
Total Costs Approved 63000
Start Date 10/1/2009
End Date 9/30/2010
IFO Name Stofko, Mark
IFO E-Mail Address mstofko@bc.pitt.edu
IACUC/IRB No. 99999
IACUC/IRB Institution University of Pittsburgh Medical Center-Health System
Entity ID No.
Report Request Date 10/31/2010
T1D NO
TypeCount
Invoices 0
Progress Reports 1
Experiments 1
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