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Articles 1 - 11 of 11
Full-Text Articles in Medicine and Health Sciences
Functional And Radioligand Binding Characterization Of The A1l-Adrenoceptor Subtype Of The Human Vas Deferens, B Davis, M Wiener, Christopher Chapple, Donna Sellers, R. Chess-Williams
Functional And Radioligand Binding Characterization Of The A1l-Adrenoceptor Subtype Of The Human Vas Deferens, B Davis, M Wiener, Christopher Chapple, Donna Sellers, R. Chess-Williams
Donna Sellers
Summary: Alpha1-adrenoceptor antagonists can cause ejaculatory dysfunction as an adverse effect. Contractions of the human vas deferens are mediated via α1A-adrenoceptors, and this study investigated whether the low affinity state of this receptor (α1L-adrenoceptor) is involved in mediating contractions of this tissue. The potency of agonists and the affinity of receptor subtype selective antagonists were determined in functional experiments and in [3H]tamsulosin binding experiments to identify the α1-adrenoceptor subtype population present in the human vas deferens. The α1A-adrenoceptor selective agonist A61603 was a full agonist and was 250-fold more potent than noradrenaline. Prazosin antagonized contractile responses to phenylephrine with a …
Onabotulinumtoxina Significantly Attenuates Bladder Afferent Nerve Firing And Inhibits Atp Release From The Urothelium, Valerie Collins, Donna Daly, Marina Liaskos, Neil Mckay, Christopher Chapple, Donna Sellers, David Grundy
Onabotulinumtoxina Significantly Attenuates Bladder Afferent Nerve Firing And Inhibits Atp Release From The Urothelium, Valerie Collins, Donna Daly, Marina Liaskos, Neil Mckay, Christopher Chapple, Donna Sellers, David Grundy
Donna Sellers
Objective To investigate the direct effect of onabotulinumtoxinA (OnaBotA) on bladder afferent nerve activity and release of ATP and acetylcholine (ACh) from the urothelium. Materials and Methods Bladder afferent nerve activity was recorded using an in vitro mouse preparation enabling simultaneous recordings of afferent nerve firing and intravesical pressure during bladder distension. Intraluminal and extraluminal ATP, ACh, and nitric oxide (NO) release were measured using the luciferin-luciferase and Amplex® Red assays (Molecular Probes, Carlsbad, CA, USA), and fluorometric assay kit, respectively. OnaBotA (2U), was applied intraluminally, during bladder distension, and its effect was monitored for 2 h after application. Whole-nerve …
Testosterone Suppresses The Expression Of Regulatory Enzymes Of Fatty Acid Synthesis And Protects Against Hepatic Steatosis In Cholesterol-Fed Androgen Deficient Mice, Daniel Kelly, Joanne Nettleship, Samia Akhtar, Samia Akhtar, Vakkat Muraleedharan, Donna Sellers, Jonathan Brooke, David Mclaren, Kevin Channer, T Hugh-Jones
Testosterone Suppresses The Expression Of Regulatory Enzymes Of Fatty Acid Synthesis And Protects Against Hepatic Steatosis In Cholesterol-Fed Androgen Deficient Mice, Daniel Kelly, Joanne Nettleship, Samia Akhtar, Samia Akhtar, Vakkat Muraleedharan, Donna Sellers, Jonathan Brooke, David Mclaren, Kevin Channer, T Hugh-Jones
Donna Sellers
Aims: Non-alcoholic fatty liver disease and its precursor hepatic steatosis is common in obesity and type-2 diabetes and is associatedwith cardiovascular disease (CVD).Men with type-2 diabetes and/or CVD have a high prevalence of testosterone deficiency. Testosterone replacement improves key cardiovascular risk factors. The effects of testosterone on hepatic steatosis are not fully understood. Main methods: Testicular feminised (Tfm) mice, which have a non-functional androgen receptor (AR) and very lowserumtestosterone levels,were used to investigate testosterone effects on high-cholesterol diet-induced hepatic steatosis. Key findings: Hepatic lipid deposition was increased in Tfmmice and orchidectomised wild-type littermates versus intact wild-type littermate controls with normal …
Muscarinic Agonists And Antagonists: Effects On The Urinary Bladder, Donna Sellers, Russ Chess-Williams
Muscarinic Agonists And Antagonists: Effects On The Urinary Bladder, Donna Sellers, Russ Chess-Williams
Donna Sellers
Voiding of the bladder is the result of a parasympathetic muscarinic receptor activation of the detrusor smooth muscle. However, the maintenance of continence and a normal bladder micturition cycle involves a complex interaction of cholinergic, adrenergic, nitrergic and peptidergic systems that is currently little understood. The cholinergic component of bladder control involves two systems, acetylcholine (ACh) released from parasympathetic nerves and ACh from non-neuronal cells within the urothelium. The actions of ACh on the bladder depend on the presence of muscarinic receptors that are located on the detrusor smooth muscle, where they cause direct (M3) and indirect (M2) contraction; pre-junctional …
Effect Of Testosterone On Inflammatory Markers In The Development Of Early Atherogenesis In The Testicular-Feminized Mouse Model, Daniel Kelly, Donna Sellers, M. Woodroofe, T. Jones, Kevin Channer
Effect Of Testosterone On Inflammatory Markers In The Development Of Early Atherogenesis In The Testicular-Feminized Mouse Model, Daniel Kelly, Donna Sellers, M. Woodroofe, T. Jones, Kevin Channer
Donna Sellers
Background: Low levels of serum testosterone in men are associated with cardiovascular disease. Clinical studies show that testosterone replacement therapy (TRT) can improve symptoms of cardiovascular disease and reduce the inflammatory burden evident in atherosclerosis.
Aim: We used an in vivo animal model to determine whether testosterone influences mediators of vascular inflammation as part of its beneficial effects on atherogenesis.
Methods: Testicular-feminized (Tfm) mice, which express low endogenous testosterone and a non-functional androgen receptor (AR), were used to assess the effect of androgen status on atheroma formation, serum lipids, and inflammatory mediators. Tfm mice were fed a high-cholesterol diet, received …
Diabetes Induced Changes In Rat Mesenchymal Stem Cells, Alexandra Stolzing, Donna Sellers, Owen Llewelyn, Andy Scutt
Diabetes Induced Changes In Rat Mesenchymal Stem Cells, Alexandra Stolzing, Donna Sellers, Owen Llewelyn, Andy Scutt
Donna Sellers
Diabetes mellitus, the single most important cause of vascular disease in the industrialized world, is also associated with bone loss and impaired fracture healing. Mesenchymal stem cells (MSCs) have the potential to differentiate into osteoblasts, chondrocytes and adipocytes and other mesenchymal cells and play a central role in bone formation and repair. Because of this, we have investigated the possibility that diabetes has direct effects on MSCs in vivo and that this might represent a cellular basis for diabetes-induced osteoporosis. We isolated MSCs from rats with streptozotocin-induced diabetes and analysed them ex vivo for their ability to proliferate and differentiate …
Spontaneous Contractions Of The Pig Urinary Bladder: The Effect Of Atp-Sensitive Potassium Channels And The Role Of The Mucosa, Hironobu Akino, Christopher Chapple, Neil Mckay, Rebecca Cross, Shigetaka Murakami, Osamu Yokoyama, Russ Chess-Williams, Donna Sellers
Spontaneous Contractions Of The Pig Urinary Bladder: The Effect Of Atp-Sensitive Potassium Channels And The Role Of The Mucosa, Hironobu Akino, Christopher Chapple, Neil Mckay, Rebecca Cross, Shigetaka Murakami, Osamu Yokoyama, Russ Chess-Williams, Donna Sellers
Donna Sellers
To investigate the influence of the mucosa on the inhibitory effects of the ATP-sensitive potassium channel (KATP channel) opener, cromakalim, on the spontaneous contractions of pig bladder strips from the bladder dome and trigone. Little is known about the influence of the mucosa on spontaneous contractions and whether the nature of these contractions differs between the bladder dome and trigone.
MATERIALS AND METHODS
Paired longitudinal strips of female pig bladders were isolated from the dome and trigone. The mucosa was removed from one strip per pair and tissues were set up in organ baths. Spontaneous activity was allowed to develop …
The Beta3-Adrenoceptor Mediates The Inhibitory Effects Of Beta-Adrenoceptor Agonists Via The Urothelium In Pig Bladder Dome, Koichi Masunaga, Christopher Chapple, Neil Mckay, Masaki Yoshida, Donna Sellers
The Beta3-Adrenoceptor Mediates The Inhibitory Effects Of Beta-Adrenoceptor Agonists Via The Urothelium In Pig Bladder Dome, Koichi Masunaga, Christopher Chapple, Neil Mckay, Masaki Yoshida, Donna Sellers
Donna Sellers
Aims: Relaxation of detrusor muscle via b-adrenoceptors may contribute to urine storage during bladder filling. Thus there is increasing interest in b-adrenoceptor agonists as a potential treatment for detrusor overactivity. The role of the urothelium in bladder responses to b-adrenoceptor agonists is not yet clear, although we have shown that these agonists have a greater inhibitory effect on detrusor contraction when the urothelium is intact. The aim was to determine which b-adrenoceptor subtype is involved in this effect.
Methods: Paired strips of pig bladder dome mucosa-intact and mucosa-denuded, were mounted in tissue baths. Relaxation responses were obtained to b-adrenoceptor agonists …
Impairment Of Rectal Afferent Mechanosensitivity In Experimental Diabetes In The Rat, M. Beyak, D. Bulmer, D. Sellers, D. Grundy
Impairment Of Rectal Afferent Mechanosensitivity In Experimental Diabetes In The Rat, M. Beyak, D. Bulmer, D. Sellers, D. Grundy
Donna Sellers
Diabetes mellitus results in neuropathy of both somatic and visceral nerves. In diabetic patients with faecal incontinence, impaired rectal sensory function, manifested by a decreased sensitivity to balloon distention is common. This may contribute to unawareness of rectal filling and incontinence. There has been little study to date of visceral mechanosensation in experimental diabetes however. We hypothesized that experimental diabetes would impair mechanosensitivity in rectal afferent nerves. Diabetes was induced in rats by i.p. injection of streptozotocin. Controls were injected with citrate. In vitro recordings were performed from rectal afferent nerves innervating isolated segments of rectum. In control animals, three …
Developments In The Pharmacotherapy Of The Overactive Bladder, Donna Sellers, Neil Mckay
Developments In The Pharmacotherapy Of The Overactive Bladder, Donna Sellers, Neil Mckay
Donna Sellers
Purpose of review
The overactive bladder is a common and distressing condition that has a significant impact on the quality of life of many people worldwide. Anticholinergics remain the first line in pharmacotherapy, however the use of these agents is hindered by adverse effects and limited efficacy. Thus there is a need for more effective treatments. Recently, there has been a move towards targeting novel pathways thought to play a role in overactivity. This review aims to provide an insight into the recent developments in pharmacotherapy of the overactive bladder.
Recent findings
With recent advances in our understanding of the …
Depressed Contractile Responses To Neurokinin A In Idiopathic But Not Neurogenic Overactive Human Detrusor Muscle, Donna Sellers, Christopher Chapple, Douglas Hay, Russell Chess-Williams
Depressed Contractile Responses To Neurokinin A In Idiopathic But Not Neurogenic Overactive Human Detrusor Muscle, Donna Sellers, Christopher Chapple, Douglas Hay, Russell Chess-Williams
Donna Sellers
Objective: The role of tachykinins such as neurokinin A in regulating bladder function is unclear, but NK2 receptors seem to mediate contraction in the human bladder and it has been suggested that these peptides may have a role in the pathophysiology of bladder dysfunction. The present study investigates neurokinin receptor-mediated contractility of detrusor muscle in the idiopathic overactive and neurogenic overactive bladder and investigates the neurokinin receptor subtypes involved.
Methods: Human bladder was obtained from patients undergoing cystectomy (normal) or clam cystoplasty (idiopathic overactive) and from patients with spinal injuries (neurogenic overactive). Strips of isolated detrusor muscle were mounted in …