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Allergy is thought to be one of the etiologic factors in otitis media. The purpose of this study was to determine the histopathologic effects of H1 histamine receptor antagonists in an experimental histamine-induced middle ear inflammation model. In group A (20 rabbits), histamine challenge followed a 3-day intramuscular pretreatment with a single dose of 0.1 ml hydroxyzine hydrochloride (50 mg/ml) per day. In group B (20 rabbits), histamine challenge followed a 3-day pretreatment with a single dose 1.2 mg desloratadine per day orally. In group C (20 rabbits), histamine challenge followed a 3-day pretreatment with a single dose 1.2 mg levocetirizine per day orally. On the fourth day after baseline otomicroscopy 0.5 ml histamine 20 mg/ml was injected transtympanically on the right. Middle ear mucosa was removed and the following parameters were assessed: edema, vascular dilatation and congestion, inflammation, acute inflammatory component, presence of eosinophils, activity of the inflammation and fibrosis. A semi-quantitative grading system of 0-3 was used for grading of all parameters and statistical analysis performed by using the Mann-Whitney non-parametric test. Group A mucosae showed lower grades of all the parameters evaluated compared with those of group B. Histopathology of the mucosae of group C showed lower grade of inflammation compared with group B with significant statistical difference for the seven parameters tested. Our data validate the use of antihistamines in the treatment of refractory OME of allergic origin. Oldest H1 antagonists can be replaced by the newest agents who counteract successfully histamine effects, without any interactions or adverse effects from central nervous system.
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The primary objective of the study was to compare the safety and efficacy of TAA aqueous with loratadine in relieving the symptoms of seasonal allergic rhinitis.
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Concentration of the global population is increasingly occurring in megacities and other developing regions, where access to medicines is increasing more rapidly than waste management systems are implemented. Because freshwater and coastal systems are influenced by wastewater effluent discharges of differential quality, exposures in aquatic systems must be considered. Here, we performed a global scanning assessment of antihistamines (AHs), a common class of medicines, in surface waters and effluents. Antihistamines were identified, literature occurrence and ecotoxicology data on AHs collated, therapeutic hazard values (THVs) calculated, and environmental exposure distributions (EEDs) of AHs compared to ecotoxicity thresholds and drug specific THVs to estimate hazards in surface waters and effluents. Literature searches of 62 different AHs in environmental matrices identified 111 unique occurrence publications of 24 specific AHs, largely from Asia-Pacific, Europe, and North America. However, the majority of surface water (63%) and effluent (85%) observations were from Europe and North America, which highlights relatively limited information from many regions, including developing countries and rapidly urbanizing areas in Africa, Latin America and Asia. Less than 10% of all observations were for estuarine or marine systems, though the majority of human populations reside close to coastal habitats. EED 5(th) and 95(th) centiles for all AHs were 2 and 212ng/L in surface water, 5 and 1308ng/L in effluent and 6 and 4287ng/L in influent, respectively. Unfortunately, global hazards and risks of AHs to non-target species remain poorly understood. However, loratadine observations in surface waters exceeded a THV without an uncertainty factor 40% of the time, indicating future research is needed to understand aquatic toxicology, hazards and risks associated with this AH. This unique global scanning study further illustrates the utility of global assessments of pharmaceuticals and other contaminants to identify chemicals requiring toxicology study and regions where environmental monitoring, assessment and management efforts appear limited and necessary.
Antihistamines are the first-line treatment for chronic urticaria (CU). However, some CU patients are relatively refractory to antihistamines. The mechanism underlying the interindividual variation is still unknown. The α-chain of the high-affinity IgE receptor is crucial to the IgE-mediated allergic response. The present study is to investigate whether FCER1A polymorphisms are associated with the risk of CSU, and to determine whether these polymorphisms influence the therapeutic efficacy of nonsedating H1-antihistamines. 191 CSU patients treated by nonsedating H1-antihistamines monotherapy (including desloratadine, mizolastine or fexofenadine) were prospectively enrolled in this study. The response to antihistamines monotherapy was assessed by urticaria activity score (UAS7) after 4 weeks of treatment. FCER1A rs2298805, rs10908703 and rs2494262 genotypes were determined by Sequenom Mass Array technology or direct sequencing. There was significant difference in the allele frequency of rs2298805A between CSU patients and 177 healthy subjects (5.3 vs 10.2 %, P = 0.012, OR = 0.491, 95 % CI 0.278-0.865), and also significant difference in the allele frequency of rs2298805A between effective and ineffective groups (7.5 vs 1.0 %, P = 0.015, OR = 8.328, 95 %CI 1.1-63.039). In addition, rs2298805 polymorphism was significantly associated with total serum IgE concentrations (P = 0.011). There were no differences in the rs10908703 and rs2494262 either between CSU patients and healthy controls, or between effective and ineffective groups. These data suggest that rs2298805 might be associated with risk for CSU and the therapeutic efficacy of nonsedating H1-antihistamines in Chinese patients with CSU.
In this study, the addition of loratadine to montelukast produced a small numerical, but not statistically significant, improvement in FEV(1) and, in general, no consistent improvement in other asthma endpoints. No improvement of montelukast + loratadine versus beclomethasone was seen in any endpoint.
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Since its discovery in 1911, histamine has been recognized as a major mediator in allergic reactions and diseases, and today antihistamines remain important agents in the treatment of these conditions. In addition to its known effects on glands, vessels and sensory nerves, recent data have provided further evidence of histamine's proinflammatory actions, which appear to be mediated mainly by H1 receptors. Thus, findings indicate that histamine is a crucial mediator in both the early and late-phase reactions of an allergic response, playing important roles in cytokine release and in the adhesion process. Histamine has been shown to increase the adhesion of leucocytes to the endothelium and to stimulate production of IL-6 and IL-8 by endothelial cells. It also increases TNF alpha-induced IL-6 production and expression of adhesion molecules. These effects can be inhibited by H1 receptor antagonists. First-generation antihistamines, though moderately effective, showed poor selectivity and caused sedation, due to their penetration of the blood-brain barrier, and other troublesome side-effects. Second-generation antihistamines such as ebastine have increased potency due to greater selectivity for histamine receptors, and improved tolerability due to lack of penetration of the blood brain barrier. Recent studies have shown ebastine 10 mg daily to be effective, safe and well tolerated in the treatment of seasonal allergic rhinitis (SAR), with a rapid onset of action, symptom relief comparable to that seen with topical azelastine or oral loratadine 10 mg o.d., cetirizine 10 mg o.d. or terfenadine 60 mg b.i.d., and no significant side-effects. Ebastine therefore offers a new option in the treatment of seasonal allergic rhinitis.
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SCH 434 QD was consistently superior to placebo in controlling the symptoms of seasonal allergic rhinitis. Composite symptom scores (total, total nasal, and total nonnasal) were reduced significantly in patients treated with SCH 434 QD as compared with placebo (p < 0.01). When compared with its individual components, reductions in mean symptom scores were consistently greater, numerically, in patients treated with SCH 434 QD than in patients who were treated with either loratadine or pseudoephedrine alone. SCH 434 QD was superior to pseudoephedrine in reducing nonnasal symptoms at all time points (p < 0.01), and superior to loratadine in relieving nasal stuffiness at end point (p < 0.01). In the physicians' evaluation of therapeutic response, the SCH 434 QD group had the greatest number of patients with a good or excellent response at end point (58%). All treatments were generally well tolerated with no serious or unusual adverse events. Insomnia and nervousness, adverse events commonly associated with pseudoephedrine, were noted in a significantly greater number of patients treated with SCH 434 QD or pseudoephedrine (p < or = 0.04) as compared with those treated with loratadine or placebo.
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Patients with allergic rhinitis and exercise induced broncho-constriction must be treated with either a beta(2)-agonist or LRTA for relief or prophylaxis of their EIB.
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This multicenter, randomized, double-blind, parallel-group study was conducted to evaluate the efficacy and safety of mizolastine in PAR compared with loratadine and placebo.