			Home About us Contact

Flare Response (flare + response)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

The Neurogenic Vasodilator Response to Endothelin-1: A Study in Human Skin In Vivo

EXPERIMENTAL PHYSIOLOGY, Issue 6 2000
Ruwani Katugampola
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 ,M ET-1 (1.43 ± 0.64 ,M, n = 5) was not significantly different from baseline levels collected prior to injection (0.86 ± 0.38 ,M) whilst that in the flare increased to reach a peak value of 2.28 ± 0.61 ,M 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 ETA/ETB 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. [source]

Influence of acupuncture on type I hypersensitivity itch and the wheal and flare response in adults with atopic eczema , a blinded, randomized, placebo-controlled, crossover trial

ALLERGY, Issue 7 2010
F. Pfab
To cite this article: Pfab F, Huss-Marp J, Gatti A, Fuqin J, Athanasiadis GI, Irnich D, Raap U, Schober W, Behrendt H, Ring J, Darsow U. Influence of acupuncture on type I hypersensitivity itch and the wheal and flare response in adults with atopic eczema , a blinded, randomized, placebo-controlled, crossover trial. Allergy 2010; 65: 903,910. Abstract Background:, Itch is a major symptom of allergic skin disease. Acupuncture has been shown to exhibit a significant effect on histamine-induced itch in healthy volunteers. We investigated the effect of acupuncture on type I hypersensitivity itch and skin reaction in a double-blind, randomized, placebo-controlled, crossover trial. Methods:, An allergen stimulus (house dust mite or grass pollen skin prick) was applied to 30 patients with atopic eczema before (direct effect) and after (preventive effect) two experimental approaches or control observation: acupuncture at points Quchi and Xuehai [verum acupuncture (VA), dominant side], ,placebo-point' acupuncture (PA, dominant side), no acupuncture (NA). Itch intensity was recorded on a visual analogue scale. After 10 min, wheal and flare size and skin perfusion (via LASER-Doppler) were measured at the stimulus site, and the validated Eppendorf Itch Questionnaire (EIQ) was answered. Results:, Mean itch intensity was significantly lower in VA (35.7 ± 6.4) compared to NA (45.9 ± 7.8) and PA (40.4 ± 5.8) regarding the direct effect; and significantly lower in VA (34.3 ± 7.1) and PA (37.8 ± 5.6) compared to NA (44.6 ± 6.2) regarding the preventive effect. In the preventive approach, mean wheal and flare size were significantly smaller in VA (0.38 ± 0.12 cm2/8.1 ± 2.0 cm2) compared to PA (0.54 ± 0.13 cm2/13.5 ± 2.8 cm2) and NA (0.73 ± 0.28 cm2/15.1 ± 4.1 cm2), and mean perfusion in VA (72.4 ± 10.7) compared to NA (84.1 ± 10.7). Mean EIQ ratings were significantly lower in VA compared to NA and PA in the treatment approach; and significantly lower in VA and PA compared to NA in the preventive approach. Conclusions:, Acupuncture at the correct points showed a significant reduction in type I hypersensitivity itch in patients with atopic eczema. With time the preventive point-specific effect diminished with regard to subjective itch sensation, whereas it increased in suppressing skin-prick reactions. [source]

Inhibition of allergen-induced wheal and flare reactions by levocetirizine and desloratadine

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2008
Nelly Frossard
What is already known about this subject ,,The reproducible and standardized histamine-induced wheal and flare model helps identify the objective effectiveness of antihistamines in humans, as well as their differences in onset and duration of action. ,,Some of the newest antihistamines have already been compared in a head-to-head setting using this model. However, their objective action at inhibiting the allergen-induced wheal and flare response has not been reported yet. What this study adds ,,The time,response study presented here shows the objective activity of two of the newest generation of antihistamines, levocetirizine and desloratadine, at inhibiting the allergen-induced wheal and flare response in a randomized, cross over, placebo-controlled trial. ,,This model is interesting to the clinical setting since allergic subjects are recruited, and the response to allergen involves mast cell degranulation and release of numerous vasoactive and pro-inflammatory mediators additionally to histamine. ,,In addition, this study reports receptor occupancy for both antihistamines at therapeutic dosage, leading to analysis of potential differences in activity. ,,This study clearly shows the potential anti-inflammatory properties of desloratadine and levocetirizine in their skin activity when allergen is the challenging agent as occurs in the clinical situation. Aims To evaluate the inhibitory activity of the new-generation antihistamines levocetirizine and desloratadine at their therapeutic doses on the allergen-induced wheal and flare reaction at 1.5 h, 4 h, 7 h, 12 h and 24 h postdose, and to measure their plasma and skin concentrations. Methods A double-blind, randomized, cross-over, placebo-controlled study in 18 allergic subjects was carried out. The time,response of the wheal and flare reaction areas under the curve (AUC) were compared by anova. Results Both antihistamines significantly (P < 0.001) inhibited the allergen-induced wheal and flare reactions compared with placebo. Levocetirizine was significantly more potent than desloratadine. Mean ± SEM wheal AUC(0,24 h) was 506.4 ± 81.0 with levocetirizine and 995.5 ± 81.0 mm2 h with desloratadine as compared with placebo (1318.5 ± 361.0 mm2 h). Flare AUC(0,24 h) was 5927.3 ± 1686.5 and 15838.2 ± 1686.5 mm2 h, respectively [P < 0.001 for both compared with placebo (22508.2 ± 7437.1 mm2 h)]. Levocetirizine showed significant inhibition of wheal and flare already at 1.5 h postdose compared with placebo (P , 0.001); desloratadine achieved a significant effect only after 4 h. The mean total plasma concentration at 12 h and 24 h after intake was higher for levocetirizine (58.1 ± 13.4 and 20.0 ± 8.1 ng ml,1, respectively) as compared with desloratadine (0.82 ± 0.24 and 0.45 ± 0.16 ng ml,1). Similarly, higher mean unbound skin concentrations were observed for levocetirizine 24 h after intake (1.80 ng g,1) than for desloratadine (0.07 ng g,1). This was associated with greater receptor occupancy for levocetirizine (54%) than desloratadine (34%) at 24 h. Conclusions Levocetirizine suppressed the cutaneous allergic reactions with a higher potency than desloratadine, which correlated with its high receptor occupancy. Receptor occupancy rather than drug affinity or plasma half-life is more representative of antihistamine potency. [source]

Inhibition of the histamine-induced weal and flare response: a valid surrogate measure for antihistamine clinical efficacy?

CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2007
P. Devillier
Summary Histamine plays a central role in allergic responses. Inhibition of the weal and flare response to histamine is a traditional pharmacodynamic tool to measure the activity of H1 -receptor antagonists. The time course and duration of cutaneous weal and flare inhibition are often used as surrogate measures of clinical efficacy. Pharmacodynamic differences among antihistamines are often interpreted to indicate differences in clinical efficacy. A systematic review of literature from 1980 to 2006 regarding the histamine induced weal and flare was undertaken. Search terms included ,histamine', ,skin test', ,weal', ,flare', and ,antihistamine'; retrieved articles were searched for relevant studies not identified initially. Data from human studies on the inhibition of the weal and flare by second-generation antihistamines were extracted and assessed. A literature search from 1980 to 2006 was undertaken for comparative studies of second-generation antihistamines in the clinical settings of allergic rhinitis (AR) and chronic idiopathic urticaria; data extracted from these studies underwent systematic review. Differences were noted among second-generation antihistamines in terms of their ability to inhibit the histamine-induced weal and flare. Corresponding differences in terms of clinical efficacy in AR and chronic urticaria were not identified following a systematic review. The reasons for the disconnect between pharmacodynamic effects and clinical efficacy may include differences between the route and concentration of histamine, the involvement of mediators other than histamine in the allergic response, and the short time course of pharmacodynamic studies. The histamine-induced weal and flare response is a pharmacodynamic test that should not be used to compare the clinical efficacy of different antihistamines, and is not an adequate alternative to clinical end-point assessments in AR or chronic idiopathic urticaria. [source]