Abstract
Overactive bladder (OAB) is a multifactorial disease that affects up to a third of the population. OAB is a syndrome where dysfunction in bladder storage presents with increased urinary urgency, frequency, and nocturia. Often OAB is diagnosed when other urinary pathophysiology is not present. The condition can be socially isolating for the sufferer. Given the majority of the symptoms associated with OAB are due to functional changes in the bladder, there is an assumption that changes in signalling molecules within the bladder may be root cause of OAB.Signalling molecules are released from the bladder urothelium, which is the outer most layer of the bladder and is in direct contact with urine stored within the bladder. These signalling molecules play a pivotal role in regulating bladder function such as relaxation and contraction of the bladder smooth muscle. The three main urothelium signalling molecules are acetylcholine (ACh), adenosine triphosphate (ATP), and nitric oxide. However, these signalling molecules when released from the urothelium are easily metabolised making detection difficult. However, their respective metabolites choline, xanthine, and nitrite, are stable and thus provide the ability to serve as indirect measure of urothelium signalling molecules in urine.
To measure the metabolites of urothelium signalling molecules, we utilised electrochemical detection, where multiple electrochemical sensors could be utilised for simultaneous detection of all metabolites within a single urine sample.
For simultaneous measurements, four carbon platinum black composite working electrodes consisting of carbon nanotube and platinum black were produced and tailored to directly detect nitrite and peroxide. Two of these electrodes were used to detect peroxide generated by choline oxidase and xanthine oxidase. The third electrode served as a null electrode as well as for the detection of nitrite. The fourth electrode is used to subtract for the nitrite sensor.
By using these four sensors we detected choline, xanthine, and nitrite in rat urine from an OAB animal model. We observed no difference in choline levels, a significant decrease in xanthine levels and significant increase in nitrite level in the urine of the OAB animal model. Both xanthine and nitrite showed clear correlations with bladder functional measures and inflammatory score.
Overall, our findings highlight that metabolites of urothelium signalling molecules can provide insight into changes with OAB that are directly related to functional changes. These findings can have significant potential in the development of a point-of-care diagnostic technology for early detection of OAB.
| Date of Award | Jul 2023 |
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| Original language | English |
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| Supervisor | Bhavik Patel (Supervisor), Dr John S. Young (Supervisor) & Anastasia Callaghan (Supervisor) |