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  • 1
    Electronic Resource
    Electronic Resource
    Pituitary adenylate cyclase activating polypeptide (PACAP) is localized in human dermal neurons and causes histamine release from skin mast cells (1998)
    Springer
    Inflammation research 47 (1998), S. 488-492 
    Details
    ISSN: 1420-908X
    Keywords: Key words: Human — Immunohistochemistry — Mast cells — Microdialysis — Neuropeptides — Skin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide homologous with vasoactive intestinal polypeptide (VIP) which is known to induce histamine release in human skin mast cells. PACAP has not been detected in human skin. The purposes of the study were to investigate the occurrence of PACAP in human skin and to evaluate the histamine releasing activity of the two common pro-PACAP products, PACAP-27 and PACAP-38.¶Material: Fourteen human surgical skin samples were obtained. PACAP and VIP were visualized by immunohistochemistry. A microdialysis technique was used to measure histamine release in intact skin samples following intradermal injections of the peptides.¶Results: PACAP and VIP were localized in dermal nerves in connection with sweat glands. Intradermal injection of 3 or 10 μm PACAP significantly released histamine. Kinetics of histamine release showed peak release 2–4 min after skin challenge. Ten μm of PACAP-27, VIP and somatostatin caused histamine release with similar efficacy, whereas PACAP-38 was less effective. Substance P was twice as efficient as PACAP-27, whereas calcitonin gene-related peptide did not release histamine.¶Conclusions: PACAP is found in human skin and is capable of releasing histamine from skin mast cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000110050363
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  • 2
    Electronic Resource
    Electronic Resource
    Measurement of histamine release from human lung tissue ex vivo by microdialysis technique (1998)
    Springer
    Inflammation research 47 (1998), S. 501-505 
    Details
    ISSN: 1420-908X
    Keywords: Key words: Microdialysis — Lung mast cells — Histamine release — Anti-IgE
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: Currently no method is available for measurement of mediator release from intact human lung. In this study, a microdialysis technique was used to measure histamine release from mast cells in human lung tissue ex vivo.¶Material: Microdialysis fibers of 216 μm were inserted into lung tissue and perfused with Krebs Ringer buffer at a rate of 3 μl/min. After a 15 min period of steady-state perfusion, anti-IgE and vehicle were injected into the lung tissue above individual fibers. Samples from each fibre were collected for 20 min at 2 min intervals. Histamine was assayed fluorometrically.¶Results: Anti-IgE concentrations of 40–40,000 U/ml dose-dependently released histamine, significant histamine release being demonstrated with anti-IgE concentrations of 400 U/ml and greater. The kinetics of histamine release showed peak values 2–8 min after the injection. Great individual responses were observed but data could be reproduced within individual donors. Monocyte chemoattractant protein-1, a potent basophil secretagogue, did not induce histamine release in lung tissue which indicated mast cells to be the histamine source. Substance P did not release histamine in the lung tissue.¶Conclusions: The microdialysis technique allowed measurements of histamine release from mast cells in intact lung ex vivo. The method may prove useful since a number of experiments can be performed in a few hours in intact lung tissue without any dispersion or enzymatic treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000110050365
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  • 3
    Electronic Resource
    Electronic Resource
    The effect of cetirizine and loratadine on codeine-induced histamine release in human skin in vivo assessed by cutaneous microdialysis (1996)
    Springer
    Inflammation research 45 (1996), S. 486-490 
    Details
    ISSN: 1420-908X
    Keywords: Histamine release ; Cetirizine ; Loratidine ; Human skin ; Microdialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective and Design To determine whether or not cetirizine and loratadine inhibit codeine- induced histamine release in human skin in vivo, we conducted a placebo-controlled double-blind trial in which histamine release was assessed by dermal microdiaysis. Subjects A group of ten normal volunteers were studied, each subject visiting the laboratory on three occasions with intervals of at least 2 weeks between visits. Treatment Cetirizine, loratadine (both 10 mg) or placebo was given orally 4h before provocation of weal and flare responses in the skin by intradermal injection of 25 μl of 3 or 10 mg/ml codeine 1 mm from the centre of individual 216 μm diameter microdialysis fibres inserted in the dermis. Methods Dialysate was collected at 2 min intervals for 4 min before and 20 min after codeine injection and histamine assayed spectrofluorometrically. Weal and flare responses to codeine were assessed in the opposite arm. Results Histamine concentrations in the microdialysis fibre outflow with 3 and 10 mg/ml codeine were maximal at 2–4 min when 910±156 and 1194±304 nM respectively were found in the placebo group. Cetirizine and loratadine did not modify either the kinetics or total histamine release while significantly (p〈0.01) inhibiting weal and flare responses. Conclusions Neither cetirizine nor loratadine inhibited codeine-induced histamine release or modified the time course of its release in human skin in vivo when given in clinically used doses which are sufficient to significantly reduce weal and flare responses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02252321
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  • 4
    Electronic Resource
    Electronic Resource
    The effect of salmeterol and salbutamol on mediator release and skin responses in immediate and late phase allergic cutaneous reactions (1999)
    Springer
    Inflammation research 48 (1999), S. 527-532 
    Details
    ISSN: 1420-908X
    Keywords: Key words: Beta-adrenergic agonists — Immediate-type hypersensitivity — Inflammatory mediators — Leucocyte chemotaxis — Skin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Background: Salmeterol is a long-acting β 2-agonist which in animal studies has been shown to possess anti-inflammatory effects on early (EAR) and late (LPR) phase allergic responses.¶Purpose: To evaluate the anti-inflammatory effects of intradermally injected salmeterol and salbutamol on clinical and biochemical EAR and LPR in human skin. ¶Methods: Measurement of wheal and flare reactions to allergen, codeine, and histamine, and LPR (induration) to allergen. Assessment of histamine and prostaglandin D2 (PGD2) release by microdialysis technique in EAR, and measurement of mediators in LPR by suction blister technique. ¶Results: Both β 2-agonists inhibited allergen-induced histamine release and wheal and flare reactions with maximum inhibition of 40-50% at 10-6M, a concentration which reduced PGD2 synthesis by approximately 55%. Histamine release by codeine and skin reactions to codeine and histamine were not or only marginally reduced. Salmeterol and salbutamol (10-6M) inhibited clinical LPR at 6h by 71% and 48%, Except for the clinical LPR, no statistical differences were found between the two drugs on any parameters. None of the drugs inhibited levels of histamine, tryptase, myeloperoxidase, or eosinophil cationic protein in LPR. ¶Conclusions: Salmeterol and salbutamol inhibited allergen-induced skin responses, and reduced mediator release in EAR but not LPR. In general, the anti-inflammatory effects of salmeterol did not differ from those induced by salbutamol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000110050498
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  • 5
    Electronic Resource
    Electronic Resource
    Cetirizine inhibits skin reactions but not mediator release in immediate and developing late-phase allergic cutaneous reactions. A double-blind, placebo-controlled study (2001)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 31 (2001), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Recent reports have indicated cetirizine, a potent H1-receptor antagonist, to possess a number of anti-inflammatory effects, e.g. inhibition of mast cell degranulation and inhibition of leucocyte migration and activation.Objective The aim of this study was to compare the effects of cetirizine on skin responses and mediator release in intact skin in immediate and developing late-phase allergic reactions by microdialysis technique.Methods Cetirizine 10 mg once daily or matching placebo were administered to 10 atopic subjects for 6 days followed by a 2-week washout in a randomized, double-blind, placebo-controlled, cross-over trial. Immediate skin test responses to allergen, codeine, and histamine and late-phase reactions to allergen were assessed. The time course of extracellular levels of inflammatory mediators in intact skin were monitored by microdialysis techniques using 2 kDa and 3 MDa cut-off fibers, respectively.Results Cetirizine significantly reduced immediate weal and flare reactions to allergen, codeine, and histamine. Injection of allergen, but not buffer controls, induced a significant release of histamine, tryptase, prostaglandin D2, total protein, and eosinophilic cationic protein. No significant increase of leukotriene B4 and myeloperoxidase was observed. Cetirizine inhibited early total protein extravasation by 40%, but this did not reach a significant level. None of the inflammatory mediators were significantly inhibited by cetirizine. Cetirizine significantly reduced the late-phase skin induration to allergen by approximately 30%.Conclusion Cetirizine potently reduced skin responses in immediate allergic reactions without inhibition of early mediators. These data indicate cetirizine to be a potent H1-receptor antagonist with no effect on mast cell activation. It did not inhibit any of the late-phase mediators, but it reduced the late skin reaction. These data suggest that mediators other than those actually measured may play a significant role in the clinical late-phase reaction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2001.01139.x
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  • 6
    Electronic Resource
    Electronic Resource
    Histamine is released in the wheal but not the flare following challenge of human skin in vivo: a microdialysis study (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 27 (1997), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background The mediator mechanisms of the cutaneous wheal and flare response, which underlies allergic skin and urticarial conditions, are controversial. The wheal results primarily from a direct effect of histamine on the local vascular bed, but to what extent does histamine diffuse within the wheal? The flare is neurogenic in origin, being disseminated within the dermis by axon reflexes, but do the neuropeptides released from the nerve endings cause the vasodilatation directly or do they induce the further release of histamine which then transduces the fiare?Objective We have addressed these questions by inserting 216 μm diameter microdialysis fibres into the dermis within the different areas of the wheal and flare to monitor changes in histamine levels provoked by intradermal injections of histamine, allergen, codeine and substance P. Twenty-one subjects participated in the investigations.Results The histamine concentration in unprovoked skin was 10.5 ± 0.6 nM. As the dialysis efficacy was 50%, this equates to tissue concentrations of 20 nM. All provicants released large amounts of histamine at the injection site, maximum histamine levels being 337–1293 nM. Diffusion of histamine within the wheai was poor, levels at 2.3 mm and 3.7 mm from the site of injection being 4–22% and 0.2–3.7% respectively of those 1 mm from the injection site. No increased histamine levels were detected in the flare with any provicant. Atraumatic delivery to the skin of histamine in infusion concentrations of 30–10000 nM caused concentration-related effects, at least 100 nM being necessary to induce a significant increase in skin blood flow, a threshold of 300–1000 being required to stimulate a visible flare and a measurable erythema, and 3000–10000 nM being the minimum for induction of a wheal. Thus the skin blood vessels and nerves are responsive to histamine, but at relatively high concentrationsConclusions These data support the theory that the flare reaction to local histamine injection or release is a neurogenic reflex not involving histamine release at its effector end.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.1997.d01-502.x
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  • 7
    Electronic Resource
    Electronic Resource
    No release of histamine and substance P in capsaicin-induced neurogenic inflammation in intact human skin in vivo: a microdialysis study (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 27 (1997), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Studies in rodents ‘skin have indicated substance P to be the main inflammatory mediator involved in neurogenic inflammation, acting partly by release of histamine from skin mast cells. The mediators released in neurogenic inflammation in human skin remain to be determined.Objectives To determine the effects of intradermally injected and topically applied capsaicin on the release of histamine and substance P and skin responses in intact human skin in vivo.Methods Extracellular skin levels of histamine and substance P were measured by microdialysis technique and assayed by enzyme and radio immunoassays. Two kinds of dialysis fibres (210μm, 2 kDa, and 500 μm, 20 kDa) were inserted intradermally into forearm skin for studies of histamine release to topically administered capsaicin and intradermally injected capsaicin and substance P.Results Baseline histamine skin levels were 8.0 ± 0.7 nM. Intradermally injected capsaicin (0.3–30μM, 7.5–750 pmol) caused significantly and dose-related flare and pain reactions, but no significant histamine release or weals. Intradermally injected substance P (1 and 3 μM, 25 and 75 pmol) released significant amounts of histamine (peak levels being 90 and 475 nM), evoked weal-and-flare reactions, but did not cause pain. Capsaicin 2% ointment, applied on the skin for 2.5 h, increased skin blood flow by 300–400% as measured by laser Doppler flowmetry, elicited a longstanding burning sensation, but did not release histamine. Substance P-like immunoreactivity (SP-LI) was below the 1.8 pM detection limit following insertion of 20 kDa dialysis fibre and after intradermal injection of capsaicin 3μM. Intradermal injection of injection of 1 μM of substance P increased SP-LI levels to values greater than 4500 pM, confirming the ability of the dialysis fibre to recover this peptide.Conclusions Capsaicin-induced neurogenic activation does not involve the release of histamine from mast cells or detectable amounts of substance P release from sensory nerves in normal human skin in vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.1997.tb01239.x
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  • 8
    Electronic Resource
    Electronic Resource
    Lower leg subcutaneous blood flow during walking and passive dependency in chronic venous insufficiency (1991)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 124 (1991), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The blood flow in the subcutaneous adipose tissue of the lower leg of eight normal subjects and 19 patients with chronic venous insufficiency was measured. The 133Xe-washout technique was used with portable CdT1(C1) detectors and a data storage unit. Only those patients with ulcers and a systolic blood pressure at the toe of ≥ 60 mm were investigated.In the controls the relative blood flow during sitting was 0.61 (range 0.35–0.80). In the patients it was 0.46 (range 0.22–0.87). This difference was not significant. During walking the blood flow increased in controls as well as in the patients compared to the value determined in the sitting position (P= 0.0078 and P= 0.0028, respectively. Wilcoxon matched-pairs test). The relative blood-flow rate during walking was 0.96 (range 0.60–1.58) in the controls, and 1.04 (range 0.49–1.46) in the patients. The difference between the normal subjects and the patients was not significant (P= 0.79).We conclude from our studies that patients with venous insufficiency are able to increase their blood flow during walking to the same extent as normal controls.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1991.tb00429.x
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  • 9
    Electronic Resource
    Electronic Resource
    Quantitative measurement of extracellular histamine concentrations in intact human skin in vivo by the microdialysis technique: methodological aspects (1997)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 52 (1997), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Petersen LJ. Quantitative measurement of extracellular histamine concentrations in intact human skin in vivo by the microdialysis technique: methodological aspects.Calculation of recovery is needed in microdialysis studies to calculate absolute concentrations of compounds in the extracellular water space. The purposes of this study were to determine the extracellular concentration of histamine in intact human skin in vivo and to study the validity of absolute histamine measurements during allergic skin reactions. A skin microdialysis technique and two calibration techniques, the no net flux method and the flow rate method, were used to quantify histamine concentrations in resting skin. To validate these techniques, skin glucose concentrations were analysed as well. In addition, the influence of vasodilation and plasma extravasation on recovery was followed after intradermal injection of codeine, a mast-cell secretagogue. As expected, both calibration methods estimated skin glucose concentrations to be identical with venous blood glucose concentrations. However, skin histamine levels could not be calculated by the no net method, because the data did not meet the theoretic assumptions of this method. In contrast, histamine data fitted theoretically with the flow rate method, and skin histamine concentrations of 18.8±2.8 nM were found to be significantly greater than plasma histamine concentrations of 4.3±0.7 nM. Within minutes after intradermal injection of codeine, recovery increased significantly in a dose-dependent fashion. Vasodilation per se did not influence recovery. In conclusion, absolute assessment of skin histamine concentrations can be made by microdialysis by the flow rate method. The validity of such an estimate and the theoretic prerequisites for the calculations are discussed. Quantitative measurement of skin histamine levels during allergic reactions cannot be performed since recovery is altered by plasma extravasation after skin challenge.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1997.tb02598.x
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  • 10
    Electronic Resource
    Electronic Resource
    Time of onset of action of acrivastine in the skin of pollen-allergic subjects (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 49 (1994), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The purpose of this study was to assess the time of onset of action of acrivastine in suppressing the wheal response to histamine (10 mg/ml) and allergen (10000 and 100000 BU/ml) in the skin prick test. Ten subjects with a well-documented allergy to pollen received single doses of 8 mg of acrivastine and placebo according to a randomized, double-blind, placebo-controlled, crossover treatment design. Duplicate skin prick tests were performed 0, 15, 20, 25, 30, and 60 min after medication. The results demonstrated a statistically significant suppression of the wheal reactions 15–20 min after medication, depending on the reaction producers used. The sum of all three producers showed a statistically significant effect on the wheal reaction 15 min after medication. The upper 95% confidence limit for time lag from dosing of acrivastine until reduction from placebo level commences was 6.5 min. The study substantiates that orally administered acrivastine has a rapid onset of action in the skin of allergic subjects. The results indicate that allergen SPT is a more sensitive tool for studying antihistaminergic activity than histamine SPT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.1994.tb00769.x
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