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المؤلفون: Geraldine F. Clough, Rachel E.B. Watson, Meneka K. Sidhu, R. C C Brooke, Peter S. Friedmann, A. Sinha, Lesley E. Rhodes
المصدر: British Journal of Dermatology. 169:645-652
مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Erythema, Indomethacin, Prostaglandin, Human skin, Dermatology, Pharmacology, Administration, Cutaneous, Nitric Oxide, Dinoprostone, Nitric oxide, Young Adult, chemistry.chemical_compound, Indometacin, medicine, Humans, Cyclooxygenase Inhibitors, Intradermal injection, Enzyme Inhibitors, Prostaglandin E2, Aged, Photosensitizing Agents, integumentary system, business.industry, Aminolevulinic Acid, Middle Aged, Healthy Volunteers, NG-Nitroarginine Methyl Ester, Photochemotherapy, chemistry, Female, Drug Eruptions, Nitric Oxide Synthase, medicine.symptom, business, Histamine, medicine.drug
الوصف: Summary Background Topical 5-aminolaevulinic acid photodynamic therapy (5-ALA-PDT) causes a clinical inflammatory response in human skin. While histamine mediates the immediate reaction, the mediators of the prolonged erythema are unknown. Objectives To look for involvement of the proinflammatory mediators prostaglandin (PG)E2 and nitric oxide (NO) in topical PDT-induced erythema in human skin. Methods A series of studies was performed in healthy volunteers (n = 35). Following definition of the erythemal time course and dose response to 5-ALA-PDT, duplicate 5-ALA dose series were iontophoresed into the skin of each ventral forearm and exposed to 100 J cm−2 broadband red light. Within subject, arms were randomized to control, or treatment with the cyclooxygenase and NO synthase inhibitors indometacin and Nω-nitro-l-arginine methyl ester (l-NAME), respectively, and the impact on 5-ALA-PDT-induced erythema was quantified. Additionally, release of PGE2 and NO was directly assessed by sampling dermal microdialysate at intervals following 5-ALA-PDT administration. Results A 5-ALA dose-related delayed erythema occurred by 3 h (r = 0·97, P
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e5cf83fe1e5379208640b812d445476Test
https://doi.org/10.1111/bjd.12562Test -
2
مصطلحات موضوعية: 0301 basic medicine, Tissue fluid, General Mathematics, Efferent, Multiphysics, Immunology, Finite Element Analysis, Models, Biological, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Mice, medicine, Fluid dynamics, Image Processing, Computer-Assisted, Animals, Homeostasis, Lymph node, General Environmental Science, Lymphatic Vessels, Pharmacology, Physics, General Neuroscience, Mathematical Concepts, 030104 developmental biology, medicine.anatomical_structure, Lymphatic system, Computational Theory and Mathematics, Node (circuits), Lymph, Lymph Nodes, General Agricultural and Biological Sciences, Software, Biomedical engineering
الوصف: The lymphatic system returns fluid to the bloodstream from the tissues to maintain tissue fluid homeostasis. Lymph nodes distributed throughout the system filter the lymphatic fluid. The afferent and efferent lymph flow conditions of lymph nodes can be measured in experiments; however, it is difficult to measure the flow within the nodes. In this paper, we present an image-based modelling approach to investigating how the internal structure of the node affects the fluid flow pathways within the node. Selective plane illumination microscopy images of murine lymph nodes are used to identify the geometry and structure of the tissue within the node and to determine the permeability of the lymph node interstitium to lymphatic fluid. Experimental data are used to determine boundary conditions and optimise the parameters for the model. The numerical simulations conducted within the model are implemented in COMSOL Multiphysics, a commercial finite element analysis software. The parameter fitting resulted in the estimate that the average permeability for lymph node tissue is of the order of magnitude of [Formula: see text]. Our modelling shows that the flow predominantly takes a direct path between the afferent and efferent lymphatics and that fluid is both filtered and absorbed across the blood vessel boundaries. The amount that is absorbed or extravasated in the model is dependent on the efferent lymphatic lumen fluid pressure.
وصف الملف: text
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a89db78023a53f9f36cd880750815c9eTest
https://eprints.soton.ac.uk/384171Test/ -
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المؤلفون: Félix García, Liliana Barandica, Pilar Brazis, Martin K. Church, Geraldine F. Clough, Anna Puigdemont
المصدر: Veterinary Dermatology. 17:169-174
مصطلحات موضوعية: Time Factors, Microdialysis, medicine.medical_treatment, Administration, Oral, Prostaglandin, Pharmacology, Histamine Release, Beagle, Dermatitis, Atopic, chemistry.chemical_compound, Dogs, In vivo, Cyclosporin a, Animals, Medicine, Dog Diseases, Ascaris suum, General Veterinary, biology, Prostaglandin D2, business.industry, biology.organism_classification, Immunosuppressive drug, chemistry, Immunology, Cyclosporine, Female, Dermatologic Agents, business, Immunosuppressive Agents, Histamine
الوصف: Dermal microdialysis, a relatively noninvasive technique, allows investigation of the changes in cellular mediators released during cutaneous allergic responses. This technique was used to evaluate the effect of cyclosporin A, an immunosuppressive drug used for treatment of canine atopic dermatitis, on the cutaneous release of two pro-inflammatory mediators following intradermal allergen challenge. Four beagle dogs spontaneously sensitized to Ascaris suum were treated for 1 month with oral cyclosporin A. At days 0, 15 and 30 of the treatment, dialysis probes were inserted into the skin of the back, and 20 microL of A. suum antigen was injected intradermally at each site. At timed intervals, dialysate was collected and assayed for histamine and prostaglandin D(2) and the wheal area was measured. Mean histamine concentration and wheal area were significantly lower at days 15 and 30 of treatment, compared with day 0. However, prostaglandin D(2) concentration was not significantly reduced. The inhibition in histamine release after intradermal challenge, by cyclosporin, confirms its anti-inflammatory action in the dog. Dermal microdialysis provides a useful tool for investigating canine allergic reactions and their modulation by drugs.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d370b487f69e0d85f0b1629eab462e8Test
https://doi.org/10.1111/j.1365-3164.2006.00511.xTest -
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المؤلفون: Geraldine F. Clough, E. F. Willis, M. K. Church
المصدر: Clinical Experimental Allergy. 34:450-455
مصطلحات موضوعية: Adult, Nedocromil, Urticaria, Sodium, Immunology, chemistry.chemical_element, Pharmacology, Histamine receptor, chemistry.chemical_compound, Ganglia, Sensory, Furosemide, Laser-Doppler Flowmetry, medicine, Humans, Immunology and Allergy, Single-Blind Method, Nedocromil Sodium, skin and connective tissue diseases, Bumetanide, Skin, Iontophoresis, business.industry, Vasodilation, medicine.anatomical_structure, chemistry, Histamine H1 Antagonists, business, Histamine, medicine.drug, Sensory nerve
الوصف: Summary Background In a previous study, iontophoresis of nedocromil sodium into human skin in vivo was shown to reduce histamine-induced itch and flare. In asthma, the Na+/K+/2Cl− cotransporter inhibitors, frusemide and bumetanide, have been reported to have many similar actions to nedocromil sodium. Objective To compare the effects of these drugs in the histamine-induced itch, flare and weal response in human skin in vivo and elucidate their site of action. Methods Nedocromil sodium, frusemide bumetanide and reversed osmosis water (control), were introduced by iontophoresis into the forearm skin of 10 volunteers in each of two single-blind studies. In study 1, histamine (20 μL of 100 μm) or vehicle was injected into the area of iontophoresis 10 min later. In study 2, histamine or vehicle was injected 5 mm outside the area of iontophoresis so the flare developed over the area of iontophoresis. Itch was scored on a visual analogue scale every 20 s for 5 min, flare areas were assessed using scanning laser Doppler imaging up to 10 min and weal was assessed by planimetry at 10 min. Results In study 1, nedocromil sodium, frusemide and bumetanide reduced itch scores by 36%, 48% and 34%, respectively, and flare areas by 17%, 26% and 15% respectively (all P
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e881dcad0dd5da834b5936b008b4f4f2Test
https://doi.org/10.1111/j.1365-2222.2004.01898.xTest -
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المؤلفون: Geraldine F. Clough, M. K. Church, K. J. Denham, Paraskevi Boutsiouki
المصدر: Inflammation Research. 52:424-427
مصطلحات موضوعية: Adult, Male, Allergy, Injections, Intradermal, Immunology, Human skin, Pharmacology, Loratadine, Levocetirizine, law.invention, chemistry.chemical_compound, Double-Blind Method, law, Anti-Allergic Agents, Laser-Doppler Flowmetry, medicine, Humans, Skin, Desloratadine, Cross-Over Studies, integumentary system, business.industry, Pruritus, medicine.disease, Crossover study, Cetirizine, chemistry, Erythema, Regional Blood Flow, Histamine H1 Antagonists, business, Histamine, medicine.drug, Flare
الوصف: A previous study showed the inhibitory effects of loratadine on histamine-induced wheal, flare and itch in human skin to be very variable between individuals. It was hypothesised that this variability may have been due to differences in the rates of metabolism of loratadine to its active form, desloratadine. This double blind, crossover study examined the effects of desloratadine in 12 healthy volunteers. Levocetirizine was used as a comparator.Desloratadine (5 mg), levocetirizine (5 mg) or placebo was taken orally 4 h before an intradermal injection of histamine (20 microL, 100 microM) or vehicle control into the forearm skin. Flare areas were assessed by scanning laser Doppler imaging before and at 30 s intervals for a period of 9 min. Wheal areas were measured by planimetry at 10 min. Itch was scored every 30 s for 5 min using a visual analogue scale.Following placebo administration, the mean (+/- SEM) wheal area at 10 min was 79.3 +/- 6.9 mm(2), mean flare area for the first 5 min following challenge 26.6 +/- 2.7 cm(2), and itch score for the same period 48.5 +/- 7.6%. The effects of desloratadine were variable between individuals, mean reductions in the wheal and flare areas being 17% (P = 0.033) and 12% (P = 0.036). Desloratadine did not reduce itch significantly. Levocetirizine was more consistent in its effects, mean reductions in wheal, flare and itch being 51%, 67% 78% respectively (all P0.001).A single dose of 5 mg levocetirizine produced more consistent and greater inhibitory effects on histamine-induced wheal, flare and itch than did 5 mg desloratadine. The difference is suggested to reflect the basic pharmacokinetics of the two drugs.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::428d72d42354818b15b868c072a2701cTest
https://doi.org/10.1007/s00011-003-1193-5Test -
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المصدر: Archives of Toxicology. 75:321-328
مصطلحات موضوعية: Adult, Male, Insecticides, Microdialysis, Adolescent, Erythema, Administration, Topical, Skin Absorption, Vasodilator Agents, Health, Toxicology and Mutagenesis, Human skin, Pharmacology, Toxicology, Norepinephrine, chemistry.chemical_compound, Forearm, In vivo, Laser-Doppler Flowmetry, medicine, Humans, Vasoconstrictor Agents, Toxicokinetics, Skin, integumentary system, Chemistry, General Medicine, Blood flow, medicine.anatomical_structure, Regional Blood Flow, Anesthesia, Malathion, Female, medicine.symptom, Gels
الوصف: Malathion [O,O-dimethyl-S-(1,2-dicarbethoxyethyl)phosphorodithioate] is an organophosphorus insecticide widely used in veterinary medicine and in humans for the treatment of lice. In this study, the rate of the percutaneous absorption of malathion has been measured in human skin, in vivo, using microdialysis. Malathion was detected in tissue dialysate within 30 min of its topical application to the skin of the volar surface of the forearm of healthy volunteers. The concentration of malathion in dialysate increased with lengthening duration of exposure to reach a steady state concentration at 2 h. Prolonged exposure to malathion caused a marked and long-lasting erythema localized to the area of contact. There was no evidence of local tissue oedema or of a neurogenically mediated flare or itch response following topical application. Reducing skin blood flow by the addition of the vasoconstrictor noradrenaline to the dialysis probe perfusate caused an eight-fold increase in the recovery of malathion in the dialysate, which failed to reach a steady state within 5 h. Together, these data confirm that malathion can be absorbed percutaneously and that its distribution within the cutaneous tissue space is influenced by local skin blood flow. They suggest that the increase in skin blood flow caused by malathion may itself play a significant role in enhancing its systemic uptake.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a8b128f15da13b6aa15b4c717fccdfb6Test
https://doi.org/10.1007/s002040100245Test -
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المؤلفون: Martin K. Church, Geraldine F. Clough, Zoe Cole
المصدر: British Journal of Pharmacology. 132:286-292
مصطلحات موضوعية: Pharmacology, medicine.medical_specialty, Microdialysis, business.industry, Degranulation, Human skin, Mast cell, chemistry.chemical_compound, medicine.anatomical_structure, Endocrinology, chemistry, Internal medicine, Medicine, Intradermal injection, Clobetasol propionate, business, Histamine, Glucocorticoid, medicine.drug
الوصف: 1. This study examines the relative contributions made by inhibition of mast cell degranulation, reduction of mast cell recruitment and maturation, and lowering the responsiveness of the vasculature to histamine, in the inhibition by glucocorticoids of the weal and flare in human skin. 2. One forearm of healthy human volunteers was treated for 24 h (n=6) or daily for 21 days (n=10) with 0.05% clobetasol propionate. The other arm served as control. Weal and flare responses were elicited by intradermal injection of 20 microl of 0.3 mM codeine. The areas of the responses were measured using scanning laser Doppler imaging. Microdialysis was used to assess histamine release. Mast cell numbers and tissue histamine content were assessed in 4-mm punch biopsies. Histamine (20 microl of 1 microM i.d.) was used to assess the status of the vasculature. 3. No significant effects were seen at 24 h. At 21 days, clobetasol reduced the areas of the codeine-induced weal and flare responses by 59 and 58% respectively (both P=0.006). Mast cell numbers were reduced by 47%, (P=0.014) and total tissue histamine content by 52% (P=0.006). Codeine-induced histamine release was reduced by 44% (P=0.022). The weal, but not the flare, induced by histamine was significantly inhibited (P=0.019). Echography revealed a 15% thinning of the skin by clobetasol. 4. These results demonstrate that reduction of the weal and flare responses to codeine following clobetasol treatment, results primarily from reduced mast cell numbers and tissue histamine content rather than inhibition by corticosteroids of mast cell degranulation.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::c0bbf01696eb17420523d2e3b1222b4bTest
https://doi.org/10.1038/sj.bjp.0703789Test -
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المؤلفون: Ruwani Katugampola, Geraldine F. Clough, Martin K. Church
المصدر: Experimental Physiology. 85:839-846
مصطلحات موضوعية: Microdialysis, biology, Chemistry, General Medicine, Pharmacology, Endothelin 1, Pallor, Bosentan, Nitric oxide, Nitric oxide synthase, chemistry.chemical_compound, Anesthesia, medicine, biology.protein, Intradermal injection, medicine.symptom, Histamine, medicine.drug
الوصف: We have investigated the mediators and mechanisms underlying the vasodilator effects of the potent vasoactive peptide, endothelin-1 (ET-1) and its isomers ET-2 and ET-3 in human skin, in vivo, using cutaneous microdialysis to quantify the release of mediators within the dermal response and scanning laser Doppler imaging to measure changes in blood flux. The effects of local anaesthesia, inhibition of nitric oxide synthase (NOS) by L-NAME and ET receptor blockade on the ET-induced vascular response were also investigated. ET-1, -2 and -3 all caused a dose-dependent area of pallor surrounded by a long-lasting flare which was accompanied by a short-lived burning pruritus. The concentration of nitric oxide (NO) in dialysate collected within the pallor response to 5 microM ET-1 (1.43 +/- 0.64 microM, n = 5) was not significantly different from baseline levels collected prior to injection (0.86 +/- 0.38 microM) whilst that in the flare increased to reach a peak value of 2.28 +/- 0.61 microM at between 4 and 10 min after intradermal injection (P < 0.004). Pretreatment with local anaesthetic slowed the development of the flare and significantly reduced its size by up to 52% at 20 min after injection (P < 0.05) but had no significant effect on the central pallor. L-NAME, delivered by dialysis also caused a significant reduction in the ET-1-induced flare (P < 0.005). Bosentan, the non-selective ET(A)/ET(B) antagonist, when given by dialysis at the site of injection, reduced the area of both the ET-1-induced pallor and surrounding flare by 41 and 26%, respectively. No significant increase in tissue histamine was measured within either the pallor or flare response to ET-1, -2 or -3. Together these data confirm that the vasodilator response to endothelin-1 in human skin is neurogenic in origin and that it is in part mediated by the local release of nitric oxide. There appears to be little evidence for the involvement of mast cell-derived histamine in the initiation or modulation of ET-induced vasodilatation, in vivo.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26e5a39ed0d059a0a6bc532e101bc8dcTest
https://doi.org/10.1017/s0958067000020893Test -
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المؤلفون: Geraldine F. Clough, Rodney Gush
المصدر: Journal of Vascular Research. 46:267-269
مصطلحات موضوعية: Time Factors, Physiology, Water flow, Skin Absorption, Vasodilator Agents, Human skin, Pharmacology, Administration, Cutaneous, Diffusion, Hyperaemia, Dermis, Laser-Doppler Flowmetry, medicine, Stratum corneum, Humans, Skin, Ultrasonography, Transdermal, Dose-Response Relationship, Drug, Iontophoresis, business.industry, Microcirculation, Models, Cardiovascular, Vasodilation, medicine.anatomical_structure, Regional Blood Flow, Drug delivery, Endothelium, Vascular, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Blood Flow Velocity
الوصف: law, the dose of drug delivered to the skin is controlled. Iontophoresis uses a small electric current to drive charged substances into the skin. Electromigration of ions during iontophoresis has also been shown to induce osmotic water flow and the convective movement of neutral or even charged molecules – a process termed electro-osmosis. It is generally held that the quantity of drug delivered depends on the magnitude and duration of the current applied, the driving force (voltage) required to achieve this dose depending on the nature of the structure of the skin and its compartments. Human skin consists of three main layers – the epidermis, dermis and hypodermis. While the stratum corneum of the epidermis, with its structured lipophilic and hydrophilic domains, constitutes the major rate-limiting layer for transdermal delivery of drugs, the dermis and its vasculature, which act as the systemic absorption site for iontophoresed drugs, present the greatest challenge when modelling transdermal iontophoretic transport. The movement of agents into and within the dermis is subject to many variables, including diffusive and electrorepulsive forces at the epidermal barrier, protein/receptor binding and drug metabolism which together modulate the presence of ‘ambient’ ions in the skin that contribute to the current flow which defines drug dose. The assessment of endothelial responsiveness to vasodilator stimuli has long been considered a surrogate by which to evaluate cardiovascular risk. Our understanding of the endothelial phenotype in health and disease and the impact or therapeutic intervention on endothelial function are largely based on the measurement of changes in vessel diameter and/or perfusion in the peripheral vasculature following perturbation using physiological and pharmacological stimuli. These tests need to be non-invasive, reproducible, repeatable and standardized between laboratories if they are to be of clinical value [1] . They also should not modulate endothelial vascular function by themselves. At the level of the microvasculature, these tests generally involve perturbation of the vasculature using reactive hyperaemia, local warming, or introduction of pharmacological agents and the subsequent monitoring of the vasoresponse [2] . Iontophoretic delivery of vaso-active substances to the skin combined with laser Doppler flowmetry or perfusion imaging has been widely used for the assessment of vascular endothelial function in both research and clinical settings. The recognized advantages of the technique are that drug delivery is non-invasive and local, thus avoiding tissue perturbation and/or systemic drug effects, and that, by controlling the duration and magnitude of the iontophoretic current based on Coulomb’s Published online: November 25, 2008
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77eec253eff9a7883c8f261ca36a65beTest
https://doi.org/10.1159/000176041Test -
10
المؤلفون: Martin K. Church, Amanda R. Bennett, Geraldine F. Clough
المصدر: Experimental Physiology. 83:431-434
مصطلحات موضوعية: Adult, Male, Microdialysis, Injections, Intradermal, Vasodilator Agents, Human skin, Pharmacology, Nitric Oxide, Osmolar Concentration, Nitric oxide, Nitroglycerin, chemistry.chemical_compound, In vivo, Humans, Enzyme Inhibitors, Skin, Transdermal, Chemistry, General Medicine, Middle Aged, Amperometry, NG-Nitroarginine Methyl Ester, Biochemistry, Female, Histamine
الوصف: Using microdialysis, we measured nitric oxide (NO) levels in healthy human skin, in vivo, before and during the local inflammatory response to histamine. Basal dialysate NO concentration, assayed using an amperometric technique, was 0.49+/-0.06 microM (mean+/-S.E.M., 21 probes, 14 subjects). Histamine injection produced transient increases in NO concentration within both the weal and flare which was blocked by the NO synthase inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME). Dialysate NO concentration also increased following transdermal delivery of the nitrosovasodilator, glyceryl trinitrate. Thus, using microdialysis, it is possible to quantify NO production in human skin in vivo and study its modulation during the acute inflammatory response.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::856af75d8806bf525d913652147fcc21Test
https://doi.org/10.1113/expphysiol.1998.sp004126Test
