Vestibular Activation In Benign Paroxysmal Positional Vertigo And Superior Semicircular Canal Dehiscence
Funder
National Health and Medical Research Council
Funding Amount
$340,350.00
Summary
Vestibular Activation in Benign Paroxysmal Positional Vertigo and Superior Semicircular Canal Dehiscence The aim of this project is to study the pathological activation of the vestibular system in benign paroxysmal positional vertigo and superior canal dehiscence in order to achieve an improved diagnosis in both conditions and a more effective treatment for benign paroxysmal positional vertigo. These diseases provide unique opportunities to study unilateral activation of an otherwise normal huma ....Vestibular Activation in Benign Paroxysmal Positional Vertigo and Superior Semicircular Canal Dehiscence The aim of this project is to study the pathological activation of the vestibular system in benign paroxysmal positional vertigo and superior canal dehiscence in order to achieve an improved diagnosis in both conditions and a more effective treatment for benign paroxysmal positional vertigo. These diseases provide unique opportunities to study unilateral activation of an otherwise normal human vestibular system. Benign paroxysmal positional vertigo and its variants is prevalent, especially amongst the elderly, as a major cause of dizziness and imbalance. These conditions describe a variety of vestibular lithiasis where free-floating otoconia misplaced in a semicircular canal cause abnormal deflection of the cupula, resulting in activation of the semicircular canal in a vestibular system during changes in gravitational head position. This study endeavours to develop a scientific basis for accurate diagnosis of benign paroxysmal positional vertigo and its variants. Online real-time 3-D recording and vector analysis of the nystagmus could be adapted to a 3-D video-oculography system for a more systematic approach to diagnosis and treatment. Thus, we aim to develop and trial a suitable particle repositioning manoeuvre using a mechanical device as treatment for patients who did not respond to the clinical Epley or Semont manoeuvre. Superior semicircular canal dehiscence permits sound or pressure to abnormally activate the vestibular system. In the superior canal dehiscence study, we seek to develop a more sensitive diagnostic test. If the click-evoked 3-D VOR is due to direct activation of the otoliths, then it offers an avenue to examine otolithic function. Understanding the mechanism of unilateral activation of a normal human vestibular system is important for the development of implantable vestibular prosthesis.Read moreRead less
Ionic Conductances In Arterioles Modulated By Endothelium-derived Factors
Funder
National Health and Medical Research Council
Funding Amount
$67,828.00
Summary
The endothelial cells which form the inside lining of blood vessels can release a number of chemicals, some of which can relax the muscle in the wall of the blood vessels, while other chemicals can make the blood vessels contract. The correct balance between the contracting chemicals and the relaxing chemicals is essential for normal healthy functioning of the vessels and therefore proper blood flow through the organs of the body, and for the maintenance of normal blood pressure. If an imbalance ....The endothelial cells which form the inside lining of blood vessels can release a number of chemicals, some of which can relax the muscle in the wall of the blood vessels, while other chemicals can make the blood vessels contract. The correct balance between the contracting chemicals and the relaxing chemicals is essential for normal healthy functioning of the vessels and therefore proper blood flow through the organs of the body, and for the maintenance of normal blood pressure. If an imbalance occurs, such as a decrease in the effectiveness of the relaxing chemicals, then the muscle in the wall of the blood vessels tends to be more contracted, and this may result in decreased blood flow and possibly increased blood pressure. Such imbalances may underlie the vascular complications of diabetes, Raynaud's Phenomenon and essential hypertension. In a recent study on the effects of relaxing chemicals released from the endothelial cells, we have discovered the effects of a chemical which can cause blood vessels to contract. The chemical identity of this factor and the mechanisms by which it causes contraction are not known. Since excess activity of this chemical would tend to contract the blood vessels and therefore raise blood pressure, it is important to determine the chemical identity of this substance, and to determine how it causes contraction. The eventual development of drugs to inhibit the actions of this chemical may be a possible means for treating some diseases of the vascular system. This study is aimed at determining how this factor causes the blood vessels to contract, and takes the first steps towards determining its identity.Read moreRead less
A Novel Ionic Current Contributing To Spasm Of Small Blood Vessels
Funder
National Health and Medical Research Council
Funding Amount
$287,500.00
Summary
Vascular smooth muscle can produce strong constrictions or spasms that can severely limit blood flow. Disorders arising from such spasms include sudden death, neurological deficits, visual and hearing loss or impairment, Raynaud's phenomenon (painful episodic contraction of the fingers and toes) and intestinal necrosis. Common mechanisms are likely to underlie the spasms associated with these disparate disorders. In a recent electrophysiological study of vascular smooth muscle, we discovered a n ....Vascular smooth muscle can produce strong constrictions or spasms that can severely limit blood flow. Disorders arising from such spasms include sudden death, neurological deficits, visual and hearing loss or impairment, Raynaud's phenomenon (painful episodic contraction of the fingers and toes) and intestinal necrosis. Common mechanisms are likely to underlie the spasms associated with these disparate disorders. In a recent electrophysiological study of vascular smooth muscle, we discovered a novel membrane current which we refer to as the plateau current. This current has a strong depolarizing influence that is likely to make a major contribution to the spasms, particularly in arterioles and small arteries which are more dependent on depolarization for contraction. Block of this current is expected to minimize the depolarization and therefore prevent or ameliorate spasm of the vessels. Thus the plateau current represents a new field of therapeutic potential for addressing vascular problems that have significant health implications. However, therapeutic manipulation of the current requires knowledge of its properties. In this project we will determine the biophysical and pharmacological properties of this current using voltage-clamp techniques. We will then use this information to assess its functional significance by recording membrane potential with intracellular microelectrodes simultaneously with contractile activity. We will also compare small vessels obtained from volunteers with or without the vasospastic disorder of Raynaud's phenomenon. Our previous work using these techniques was described in J Physiol as a microelectrode, patch clamp and myograph study of the highest quality and of supreme technical difficulty and scored a Top-Ten hit rate. Since we are the only ones to record the plateau current, we are in a unique position to make significant progress to our understanding of contraction, including spasm, in small blood vessels.Read moreRead less