A5064256590- Glaucoma and retinal disorders
- Inflammatory mediators and NSAID effects
- Receptor Mechanisms and Signaling
- Eicosanoids and Hypertension Pharmacology
- Nitric Oxide and Endothelin Effects
- Cannabis and Cannabinoid Research
- Ocular Surface and Contact Lens
- Estrogen and related hormone effects
- Asthma and respiratory diseases
- Alcohol Consumption and Health Effects
- Neuropeptides and Animal Physiology
- Urticaria and Related Conditions
- Hormonal and reproductive studies
- Allergic Rhinitis and Sensitization
- Peroxisome Proliferator-Activated Receptors
- melanin and skin pigmentation
- Mast cells and histamine
- Retinal Diseases and Treatments
- Adipose Tissue and Metabolism
- Forensic Toxicology and Drug Analysis
- Proteoglycans and glycosaminoglycans research
- Olfactory and Sensory Function Studies
- Skin Protection and Aging
- Ion Channels and Receptors
- Neuroscience and Neuropharmacology Research
Imperial College London
2015-2024
Allergan (Ireland)
2002-2023
Allergan (United States)
2010-2022
Bradford Royal Infirmary
2020
University of Bradford
2020
Manchester Academic Health Science Centre
2020
University of Manchester
2020
DuPont (United States)
2006-2013
Allergan (Switzerland)
2012
Institute of Applied Science and Intelligent Systems
2007
N-arachidonoyl-serotonin (AA-5-HT) is an inhibitor of fatty acid amide hydrolase (FAAH)-catalysed hydrolysis the endocannabinoid/ endovanilloid compound, anandamide (AEA). We investigated if AA-5-HT antagonizes transient receptor potential vanilloid-1 (TRPV1) channel and, as FAAH and TRPV1 are targets for analgesic compounds, it exerts analgesia in rodent models hyperalgesia.AA-5-HT was tested vitro, on HEK-293 cells overexpressing human or rat recombinant receptor, vivo, rats mice treated...
To determine whether dexamethasone (DEX)-induced ocular hypertension (OHT) in mice mimics the hallmarks of steroid-induced glaucoma (SIG) humans, including reduced conventional outflow facility (C), increased extracellular matrix (ECM), and myofibroblasts within pathway.Osmotic mini-pumps were implanted subcutaneously into C57BL/6J for systemic delivery DEX (3-4 mg/kg/d, n = 31 mice) or vehicle (n 28). IOP was measured weekly by rebound tonometry. After 3 to 4 weeks, euthanized eyes...
Background Improved quality of life (QoL) is a desirable outcome cardiac surgery. The aim the current study was to measure association between recovery 3 days after surgery and QoL measured months later. Methods After obtaining ethics committee approval consent, 120 adult surgical patients were studied. A 40-item score (QoR-40) used postoperative health status on 1-3 1 month using short-form survey (SF-36) at effect size (delta mean/SD) define responsiveness, clinically important difference...
Abstract The motility of isolated normal human peripheral blood eosinophils and neutrophils in response to exogenous leukotrienes B4 D4 was examined by means a modified under-agarose technique novel quantitative sampling strategy. Leukotriene potent chemoattractant for eosinophils, with significant threshold chemotactic effect evident at 10-10 M. abolition eosinophil chemotaxis the selective peptide-leukotriene-antagonist SK&F 104353 indicated pharmacological specificity leukotriene...
Replacement of the carboxylic acid group prostaglandin (PG) F(2alpha) with a nonacidic moiety, such as hydroxyl, methoxy, or amido, results in compounds unique pharmacology. Bimatoprost (AGN 192024) is also pharmacologically novel PGF(2alpha) analog, where replaced by neutral ethylamide substituent. potently contracted feline lung parenchymal preparation (EC(50) value 35-55 nM) but exhibited no meaningful activity variety PG-sensitive tissue and cell preparations. Its seemed unrelated to FP...
We investigated the formation of PGF2α 1-ethanolamide, PGE2 and PGD2 1-ethanolamide (prostamides F2α, E2, D2, respectively) in liver, lung, kidney, small intestine after a single intravenous bolus administration 50 mg/kg anandamide to normal fatty acid amide hydrolase knockout (FAAH −/−) male mice. One group three mice was not dosed (naïve) while another received injection anandamide. Three FAAH −/− also an After 30 min, were harvested processed by liquid-liquid extraction. The...
Mouse models are useful for glaucoma research, but it is unclear whether intraocular pressure (IOP) regulation in mice operates through mechanisms similar to those humans. Our goal was determine pharmacologic compounds that affect conventional outflow facility human eyes exert effects C57BL/6 mice.A computerized perfusion system used measure enucleated mouse ex vivo. Paired were perfused sequentially, either immediately after enucleation or 3 hours storage at 4°C. Three groups of experiments...
purpose. To investigate long-term changes in the anterior segment of primate eyes treated for one year with different prostaglandin agonists and a prostamide. The results were compared those obtained after vehicle treatment untreated controls. methods. Sixteen young cynomolgus monkeys unilaterally topically 1 either bimatoprost 0.03% (prostamide), sulprostone (EP3/EP1 agonist), AH13205 0.1% (EP2 or latanoprost 0.005% (FP which all lower IOP this species at doses applied. Four animals only....
An FP prostanoid receptor isoform, which appears to arise from alternative mRNA splicing, has been cloned a mid-cycle ovine large cell corpus luteum library. The named the FPB receptor, is identical original FPA, throughout seven transmembrane domains, but diverges nine amino acids into carboxyl terminus. In contrast whose terminus continues for another 46 beyond shared residues, terminates after only one acid. FPA isoform by failure utilize potential splice site, while 3.2-kilobase pair...
The polymerase chain reaction (PCR) was used in combination with plaque hybridization analysis to clone four variants of the EP 3 prostaglandin receptor from a human small intestine cDNA library. Three these variants, i.e. 3A , 3E and 3D share same primary amino acid sequence except for their carboxyl termini, which diverge one another at point, approximately 10 acids away end seventh membrane spanning domain receptor. fourth variant (EP 3A1 ) has nucleotide coding identical but completely...
A prostamide analogue, bimatoprost, has been shown to be effective in reducing intraocular pressure, but its precise mechanism of action remains unclear. Hence, elucidate the molecular mechanisms this effect we focused on pharmacologically characterizing prostaglandin FP receptor (FP) and variant (altFP) complexes.FP mRNA variants were identified by reverse transcription-polymerase chain reaction. The FP-altFP4 heterodimers established HEK293/EBNA cells co-expressing altFP4 variants....
To investigate the ocular hypotensive effect of prostanoid EP2 receptor agonist butaprost and to establish its mechanism action.All experiments were performed in cynomolgus monkeys after topical application (0.1%). The effects on aqueous humor flow determined by fluorophotometry. Total outflow facility was measured two-level, constant-pressure perfusion method, uveoscleral FITC-labeled dextran through anterior chamber. Effects morphology studied tissue fixation with transcardial...
Despite structural similarity with prostaglandin F(2 alpha), the ocular hypotensive agent bimatoprost (Lumigan; Allergan, Inc., Irvine, CA) shows unique pharmacology in vitro and functional activity vivo. Unfortunately, precise mechanisms that underlie bimatoprost's distinctive impact on aqueous humor dynamics are unclear. The purpose of present study was to investigate effects a novel prostamide-selective antagonist AGN 211334 human conventional drainage.Two model systems were used test...
The role of histamine H 1 and 2 ‐receptors in mediating the cutaneous inflammatory response produced by exogenous release endogenous from mast cells has been investigated a method which permits simultaneous, quantitative measurement vasodilatation, vascular permeability oedema formation. Histamine selective ‐receptor agonist, 2‐(2‐aminoethyl) pyridine, both increased formation whereas dimaprit, only vasodilatation. Mepyramine cimetidine reduced vasodilatation to histamine, combination...
Balding causes widespread psychological distress but is poorly controlled. The commonest treatment, minoxidil, was originally an antihypertensive drug that promoted unwanted hair. We hypothesized another serendipitous discovery, increased eyelash growth side-effects of prostamide F2α-related eyedrops for glaucoma, may be relevant scalp alopecias. Eyelash hairs and follicles are highly specialized remain unaffected by androgens inhibit stimulate many others. Therefore, we investigated whether...