A5029476594- Ion channel regulation and function
- Urinary Bladder and Prostate Research
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Adenosine and Purinergic Signaling
- Advancements in Transdermal Drug Delivery
- Neuroscience of respiration and sleep
- Cardiac electrophysiology and arrhythmias
- Connexins and lens biology
- Neuroscience and Neural Engineering
- Lipid Membrane Structure and Behavior
- Nicotinic Acetylcholine Receptors Study
- Phytochemical Studies and Bioactivities
- Photoreceptor and optogenetics research
- Neurobiology and Insect Physiology Research
- Dermatology and Skin Diseases
- Contact Dermatitis and Allergies
- Advanced Fluorescence Microscopy Techniques
- Pain Mechanisms and Treatments
- Transgenic Plants and Applications
- Phytochemistry and Bioactive Compounds
- RNA Interference and Gene Delivery
- Heart Rate Variability and Autonomic Control
- Cellular transport and secretion
- Neurotransmitter Receptor Influence on Behavior
University of Birmingham
2014-2024
University of Oxford
2002-2019
Canterbury Christ Church University
2018-2019
Indian Institute of Science Bangalore
2019
Flinders University
2019
University of Missouri
2019
Birmingham Dental Hospital
2016
Cardiff University
2005-2007
Mansfield University
2005
Welsh Government
2004
Background The skin represents an accessible somatic tissue for therapeutic gene transfer. superficial lipophilic layer of the skin, stratum corneum, however, constitutes a major obstacle to cutaneous delivery charged macromolecules such as DNA. Objectives To determine whether silicon‐based microneedles, microfabricated via novel isotropic etching/BOSCH reaction process, could generate microchannels in sufficient dimensions facilitate access lipid : polycation pDNA (LPD) nonviral therapy...
Oxaliplatin, an effective cytotoxic treatment in combination with 5‐fluorouracil for colorectal cancer, is associated sensory, motor and autonomic neurotoxicity. Motor symptoms include hyperexcitability while effects urinary retention, but the cause of these side‐effects unknown. We examined on nerve function mouse hemidiaphragm system vas deferens. In diaphragm, oxaliplatin (0.5 m M ) induced multiple endplate potentials (EPPs) following a single stimulus, was increase spontaneous miniature...
The stratum corneum (SC) represents a significant barrier to the delivery of gene therapy formulations. In order realise potential therapeutic cutaneous transfer, strategies are required overcome this exclusion effect. This study investigates ability microfabricated silicon microneedle arrays create micron-sized channels through SC ex vivo human skin and resulting conduits facilitate localised charged macromolecules plasmid DNA (pDNA). Microscopic studies microneedle-treated epidermal...
The detection of several different neurotransmitters with the same sensor in real-time would be a powerful asset to field neurochemistry. We have developed detector for broad range including amino acids, catecholamines, and nucleotides, which relies on reversible binding analytes copper(II) complex within an engineered protein nanopore.
Microneedle arrays increase skin permeability by forming channels through the outer physical barrier, without stimulating pain receptors populating underlying dermis. It was postulated that microneedle could facilitate transfer of DNA to human epidermis for cutaneous gene therapy applications. Platinum-coated "wet-etch" silicon microneedles were shown be appropriate dimensions create microconduits, approximately 50 μm in diameter, extending stratum corneum (SC) and viable epidermis....
A confocal Ca 2+ imaging technique has been used to detect ATP release from individual sympathetic varicosities on the same nerve terminal branch. Varicose terminals and smooth muscle cells in mouse vas deferens were loaded with indicator Oregon Green 488 BAPTA‐1. Field (nerve) stimulation evoked discrete, focal increases [Ca ] adjacent identified varicosities. These have termed ‘neuroeffector transients’ (NCTs). NCTs abolished by α,β‐methylene (1 μM), but not nifedipine μM) or prazosin (100...
The influence of spherical aberration on axial imaging confocal reflection microscopy is investigated. In particular, the effects lens aperture size and first three orders are inspected. It shown both theoretically experimentally that aberrated response can be improved by slightly reducing size. experimental results concerning effect tube length compensation also given.
Spontaneous purinergic neurotransmission was characterized in the mouse urinary bladder, a model for pathological or ageing human bladder. Intracellular electrophysiological recording from smooth muscle cells of detrusor revealed spontaneous depolarizations, distinguishable action potentials (sAPs) by their amplitude (< 40 mV) and insensitivity to L‐type Ca 2+ channel blocker nifedipine (1 μ m ) (100 ± 29%). depolarizations were abolished P2X 1 receptor antagonist NF449 (10 (frequency 8.5...
Urinary incontinence is associated with enhanced spontaneous phasic contractions of the detrusor smooth muscle (DSM). Although a complete understanding etiology these not yet established, it suggested that spontaneously evoked action potentials (sAPs) in DSM cells initiate and modulate contractions. In order to further our ionic mechanisms underlying sAP generation, we present here biophysically detailed computational model single cell. First, constructed mathematical models for nine ion...
The sympathetic nerve terminals of the mouse vas deferens were loaded with calcium indicator Oregon Green 488 BAPTA‐1 by orthograde transport along postganglionic nerves. Changes in concentration varicosity (Δ[Ca 2+ ] v ) determined following single impulses, and short (5‐impulse) long (200‐impulse) trains at 5 Hz. All varicosities showed a significant Δ[Ca response to every impulse. elevated declined two phases similar kinetics for all varicosities: fast phase (time constant, 0.42 ± 0.05 s)...
Background The left atrial posterior wall (LAPW) is potentially an important area for the development and maintenance of fibrillation. We assessed whether there are regional electrical differences throughout murine myocardium that could underlie in arrhythmia susceptibility. Methods used high-resolution optical mapping sharp microelectrode recordings to quantify activation repolarisation within intact, superfused atrium quantified ion channel mRNA expression by Taqman Low Density Array. also...
Abstract Background: Despite the rarity of pheochromocytoma, diagnosis is important because dangers uncontrolled severe hypertension and availability very effective surgical treatment. Urinary or plasma catecholamines catecholamine derivatives are commonly used to screen for pheochromocytomas before imaging, but data from 24-h urinary metanephrine results, patient age, sex may better predict tumors in populations with a low pretest probability. Methods: We retrospectively studied outcomes an...
BACKGROUND AND PURPOSE The acute effects of PGE 2 on bladder smooth muscle and nerves were examined to determine the origin ‐induced spontaneous rhythmic contractions. EXPERIMENTAL APPROACH Contraction studies, confocal Ca 2+ imaging electrophysiological recordings in strips mouse urinary used differentiate efferent nerves. KEY RESULTS (50 µM) increased tone caused phasic contractions detrusor strips. Confocal showed that frequency whole‐cell transients (WCTs) (72 ± 5%) intracellular it...
1 1. Action potential-evoked Ca2+ transients in postganglionic sympathetic axon bundles mouse vas deferens have been characterized using confocal microscopy and imaging. 2 Axonal were tetrodotoxin sensitive. The amplitude depended on both the frequency of stimulation number stimuli a train. 3 Removal extracellular abolished transient. Cd2+ (100 μm) inhibited transient by 78 ± 10 %. N-type channel blocker ω-conotoxin GVIA (0.1 reduced −35 4 %, whereas nifedipine (10 μm; L-type) MVIIC P/Q...
The anticholinergic propiverine (1-methyl-4-piperidyl diphenylpropoxyacetate), which is used for the treatment of overactive bladder syndrome, has functionally active metabolites [M-1 diphenylpropoxyacetate <i>N</i>-oxide) and M-2 benzilate <i>N</i>-oxide)], but site actions these uncertain. Propiverine rapidly absorbed after oral administration extensively biotransformed in liver, giving rise to several (M-1 M-2). This study determines effect M-1 on voltage-dependent nifedipine-sensitive...