Drugs online research references
Clin Exp Allergy. 1995 Aug;25(8):729-36.
Leukotriene B4 production by blood neutrophils in allergic rhinitis--effects of cetirizine.
Cheria-Sammari S, Aloui R, Gormand F, Chabannes B, Gallet H, Grosclaude M, Melac M, Rihoux JP, Perrin-Fayolle M, Lagarde M, et al.
Centre Hospitalier Lyon-Sud, Laboratoire D'Immuno-allergologie, Unite INSERM U352, Pierre-Benite, France.
BACKGROUND: Mucosal inflammatory processes in late phase of allergic diseases involve cytokine production, cell adhesion molecule overexpression and release of inflammatory mediators with chemotactic activity, such as leukotriene B4 (LTB4). We had previously observed increased production of LTB4 by neutrophils in patients with allergic rhinitis and discussed the role of granulocyte macrophage-colony stimulating factor (GM-CSF) priming. Some antihistaminic compounds were shown to diminish the production of leukotrienes by neutrophils. OBJECTIVES: In a first step, we evaluated in ex vivo and in vitro studies, the effects of cetirizine on LTB4 production by blood neutrophils from allergic and healthy subjects. In a second step, we studied the in vitro effect of cetirizine on LTB4 production by neutrophils from healthy subjects during GM-CSF priming of these cells. METHODS: Neutrophils from both populations were purified from venous blood and LTB4 production was measured using high performance liquid cromatography (HPLC) method. RESULTS: In ex vivo studies, cetirizine treatment induced a decreased LTB4 production by neutrophils in allergic rhinitis. This effect of decreased LTB4 production was reproduced in vitro with 10(-8)-10(-6)M cetirizine. Nevertheless, this anti-H1 compound had no effect on neutrophil priming with GM-CSF. CONCLUSION: As LTB4 is an important chemotactic factor, Cetirizine could act on inflammatory cell recruitment by inhibiting LTB4 production by neutrophils.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7584684&dopt=Abstract
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Allergy. 1995 Feb;50(2):166-73.
Nasal histamine challenge in nonallergic and allergic subjects evaluated by acoustic rhinometry.
Hilberg O, Grymer LF, Pedersen OF.
Institute of Environmental and Occupational Medicine, University of Aarhus, Denmark.
Nasal patency shows spontaneous variations but is influenced by a number of factors like exercise and allergic conditions. Nasal histamine challenge has been used to define nasal hypersensitivity. We have applied acoustic rhinometry as a new objective method to study the spontaneous variations of the nasal mucosa and its response to histamine challenge in 12 nonallergic subjects and 12 subjects with nasal allergy to pollen, but out of the pollen season. Measurements of the minimum cross-sectional area and the volume of the nasal cavities were done every 15 min for 6 h. More pronounced spontaneous variations, defined by the coefficient of variation of the measurements, were encountered in the allergic than in the nonallergic subjects, especially with regard to the minimum cross-sectional areas in the nasal cavities (P < 0.02). Allergic subjects showed increased sensitivity to histamine, as compared with nonallergic subjects, during low-concentration (0.1%) challenge (P < 0.05) and a prolonged effect of histamine challenge (P = 0.01). Antihistamine (cetirizine) had a significant effect on the histamine-induced symptoms and decrease of nasal dimensions during histamine challenge, but no significant effect on pollen-induced changes. In the allergic group, the decrease in minimum area during allergen provocation correlated with the level of specific IgE (r = 0.81; P = 0.0015).
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7604941&dopt=Abstract
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Inflamm Res. 1995 Feb;44(2):92-7.
Inhibition of mediator release in RBL-2H3 cells by some H1-antagonist derived anti-allergic drugs: relation to lipophilicity and membrane effects.
Fischer MJ, Paulussen JJ, Horbach DA, Roelofsen EP, van Miltenburg JC, de Mol NJ, Janssen LH.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Utrecht University, The Netherlands.
In a model for mucosal mast cells (RBL-2H3 cells) a set H1-antagonist derived anti-allergic drugs containing a diphenylmethyl piperazinyl moiety was examined for their ability to inhibit release of the mediator beta-hexosaminidase. Cells were activated with antigen or the calcium ionophore A23187, whether or not in combination with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Oxatomide, hydroxyzine and cetirizine inhibit the antigen induced beta-hexosaminidase release. The release triggered by A23187, whether or not in combination with TPA is hardly influenced by the compounds. A biphasic dependence of the inhibition of exocytosis in RBL cells on lipophilicity is observed with the optimum at log P is 5-6. The extremely lipophilic compounds meclozine and buclizine are not active in this model. pH dependence of the effect of the drugs shows that especially the uncharged species are active in inhibiting exocytosis. The investigated compounds show an effect on phase transitions in L-alpha-phosphatidylcholine dipalmitoyl liposomes as assayed with differential scanning calorimetry (DSC). For the less extremely lipophilic compounds the induced changes in the phospholipid membranes increased with lipophilicity. The relation between structural features of the drug and the interaction with phospholipids is discussed in view of the DSC results. We conclude that location of the active drugs at the membrane or the membrane/protein interface is important for the inhibiting activity on exocytosis. This could affect several membrane related processes, which are abundant in the early phases of the IgE-mediated signal transduction process.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7655991&dopt=Abstract
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