Cellular Mechanisms Of Pacemaking In The Upper Urinary Tract: Effects Of Sensory Neuropeptides And Prostaglandins
Funder
National Health and Medical Research Council
Funding Amount
$80,680.00
Summary
The mammalian upper urinary tract (UUT) serves to propel urine from the renal pelvis within the kidney through the ureter to the bladder, where it is stored until micturition. This propulsion of urine from the renal pelvis to the bladder occurs by the means of spontaneous peristaltic contractions in the smooth muscle wall of the UUT, intimately dependent on the localized release of prostaglandins. Approximately 10% of the population suffer from renal calculi (kidney stones) at some stage of thei ....The mammalian upper urinary tract (UUT) serves to propel urine from the renal pelvis within the kidney through the ureter to the bladder, where it is stored until micturition. This propulsion of urine from the renal pelvis to the bladder occurs by the means of spontaneous peristaltic contractions in the smooth muscle wall of the UUT, intimately dependent on the localized release of prostaglandins. Approximately 10% of the population suffer from renal calculi (kidney stones) at some stage of their lifetime, with men being 2-4 times more likely than women to have calculi. Pain management of renal colic usually involves the prescribing of strong analgesics, and antispasmodic and nonsteroidal anti-inflammatory agents. Most stones are expelled spontaneously if they are small. Larger stones require interventions such as fragmentation (extracorpereal lithotripsy), which is an out patient procedure, or physical removal, using ureterscopes or endoscopes or open surgery under general anesthesia; procedures usually requiring hospital stays of 2-7 days. This project will provide valuable information on the mechanisms by which sensory nerves and endogenous prostaglandins control motility in the mammalian UUT. In particular, these studies will contribute to the search of specific anti-inflammatory agents which will affect particular aspects of UUT motility. A clearer understanding of the cellular origin of UUT rhythmicity will lead to more informed non-surgical interventions to encourage the passing of painful calculi. Such information will also aid in the treatments of other forms of renal colic, during ureteric obstruction, and urinary tract infection. Ureteric stasis is an important condition to avoid, if left untreated permanent kidney damage usually occurs within 6 weeks.Read moreRead less
Endometriosis affects up to 10% of reproductive aged women causing a range of debilitating symptoms including pelvic pain and infertility. Our team has discovered that small nerve fibres can be found in the endometrium of women with endometriosis that are not present in women without the condition. We will investigate how these nerve fibres grow and the mechanisms of pain generation. This will potentially allow the development of more targeted and effective treatment modalities.
We are able to identify and discriminate objects in the world because of exquisitely detailed and rapid processing of sensory information by neurons in the cortex of the brain. In this project we will examine these operations in neurons in the cortex that receive input from the large face whiskers of the rat. These whiskers are used for fine-grain discrimination and for gauging distance. They are deflected by being actively moved, under muscle control, over objects (active touch) or by being pas ....We are able to identify and discriminate objects in the world because of exquisitely detailed and rapid processing of sensory information by neurons in the cortex of the brain. In this project we will examine these operations in neurons in the cortex that receive input from the large face whiskers of the rat. These whiskers are used for fine-grain discrimination and for gauging distance. They are deflected by being actively moved, under muscle control, over objects (active touch) or by being passively deflected by objects. Deflection results in inputs to the brain that are processed to form the neural basis for very finely detailed perceptual behaviour. In rats, with impoverished visual and auditory senses, the whiskers are the major sensory system for interacting with the world, and are used in navigating the environment and in finding and distinguishing foods. Thus they contribute strongly to the remarkable success of this species. This elegant sensory system has a number of advantages that make it a very good model for the study of brain mechanisms responsible for active fine-grain sensory function. We plan to take advantage of the unique features of this system to define the information processing that occurs in the cortex in this elegantly complex system. This will address an issue relevant to all sensory systems - namely the neural basis of complex fine grain perceptual behaviour. Understanding the mechanisms underlying active tactile perception also has relevance to clinical conditions involving deficits in active touch e.g., in diabetic polyneuropathy (which eventually affects ~50% of diabetics), in leprosy (in which an early sign is damage to active touch). Knowledge of the core brain processes in active touch gained in this study could eventually underpin the ameliorative technologies for such deficits.Read moreRead less
The Role Of Adipokines In Modulation Of Gastric Vagal Afferent Satiety Signals
Funder
National Health and Medical Research Council
Funding Amount
$624,535.00
Summary
When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals are disordered in obesity and may be influenced by factors released from fat stores in the body. The aim of this project is to determine how these factors interact with gastric nerve satiety signals and thus identify targets for the pharmacological treatment of obesity.
Circadian Control Of Peripheral Gastric Satiety Signals
Funder
National Health and Medical Research Council
Funding Amount
$701,010.00
Summary
When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals exhibit circadian variations. The aim of this project is to determine circadian control of gastric nerve satiety signals and to determine how this is affected by obesity and what happens when you disrupt circadian rhythm. This will ultimately identify targets and treatment regimes for the pharmacological treatment of o ....When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals exhibit circadian variations. The aim of this project is to determine circadian control of gastric nerve satiety signals and to determine how this is affected by obesity and what happens when you disrupt circadian rhythm. This will ultimately identify targets and treatment regimes for the pharmacological treatment of obesity.Read moreRead less
Obesity is a looming health crisis for Australians; it increases the chances of many serious diseases including diabetes, cancer, stroke and heart disease. Obesity occurs when the amount of energy consumed in food is greater than the energy used over an extended period. Because human beings usually get most of their food in a few meals each day, the size of those meals is very important. Deciding when to stop eating can exert a powerful control on energy intake. It is well known that nutrients r ....Obesity is a looming health crisis for Australians; it increases the chances of many serious diseases including diabetes, cancer, stroke and heart disease. Obesity occurs when the amount of energy consumed in food is greater than the energy used over an extended period. Because human beings usually get most of their food in a few meals each day, the size of those meals is very important. Deciding when to stop eating can exert a powerful control on energy intake. It is well known that nutrients reaching the gut cause the release of hormones from cells in the lining of the stomach and intestine. These hormones tell the brain when enough food has been consumed. It used to be thought that the hormones travelled in the blood stream to affect the brain directly. Recently, it has become clear that much of their effect is actually carried by sensory neurons with endings in the lining of the gut. The hormones have a powerful effect the sensory nerve fibres which then send electrical signals in nerve fibres running in the vagus nerve to the brain. Here they make connections which eventually influence the centres that control feeding. There is much to understand about how hormones affect the sensory nerve endings in the wall of the gut, whether all nerve fibres are affected the same way and what sort of information is conveyed to the brain. This project will use electrophysiological methods to identify which nerve fibres are activated by hormones, whether different hormones affect different nerve fibres, which nutrients activate particular nerve fibres and whether nerve fibres make selective contacts with particular hormone-releasing cells. These questions are important for understanding how we normally stop feeding and how drugs might be designed to cause feelings of fullness earlier in each meal.Read moreRead less
Interactions Of Gastric Hormones With Vagal Afferent Pathways And The Role Of This System In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$550,918.00
Summary
When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals are disordered in obesity and this project aims to find out how to correct this problem in this modern day epidemic.