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Non-specific cough is defined as non-productive cough in the absence of identifiable respiratory disease or known aetiology. It is commonly seen in paediatric practice. These children are treated with a variety of therapies including anti-histamines. Also, anti-histamines are advocated as an empirical treatment in adults with chronic cough.
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A double-blind, placebo-controlled cross-over study (n = 12) was followed. After each treatment 30 biological units (BUs) of Dermatophagoides pteronyssinus or Phleum pratense were injected intradermally and the early (15 min) and late-phase response sizes (6 and 24 h) were measured. Skin biopsies were taken at 24 h for immunocytochemistry and in situ hybridization.
We are interested in understanding the pathogenesis of the cutaneous IgE-mediated late phase reaction. A double-blind, placebo-controlled, randomized cross-over study with 10 subjects of the effect of the non-sedating antihistamine, terfenadine (Selddane), on the cutaneous reaction to antigen (ragweed or mixed grass) administered intradermally and over denuded blister bases was performed. The activity of terfenadine on anti-IgE-induced mediator release from the skin mast cell, lung mast cell and basophil was also examined in vitro. Terfenadine significantly inhibited the size of the cutaneous reaction at every hour between hours 1 and 9 (hr 9, control 2250 +/- 500 mm2 vs drug 1250 +/- 250 mm2, P < 0.01, n = 10) and showed some inhibitory effect at hours 10-12. While terfenadine blocks histamine release after nasal antigen challenge the release of mediators at skin blister sites was unaffected. The infiltration of leucocytes into the blister supernatant was unaffected by terfenadine although previous studies have shown significant inhibition with another antihistamine, cetirizine. In vitro, terfenadine, like other antihistamines, was found to have inhibitory activity on anti-IgE-induced mediator release at concentrations of 10(-4)-10(-5) M in lung and skin mast cells and basophils. We conclude that the effects of the newer antihistamines on cellular movement into the skin may be diverse, that terfenadine may show organ specificity in vivo and that terfenadine significantly decreases both the early and late gross inflammatory response of the skin to antigen. We cannot, as yet, explain the mechanism(s) by which this occurs.
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Allergic rhinitis is a common airways hypersensitivity disease. Histamine and leukotrienes are involved in the pathogenesis of allergic rhinitis. Conventional treatments include topical steroids and antihistamines. Due to the adverse effects of these treatments, new drugs like leukotriene receptor antagonists are being investigated for the treatment of allergic rhinitis. A total of 90 patients suffering from allergic rhinitis were enrolled in this prospective, randomized, controlled study. Patients were divided randomly into three groups of 30 patients each. Group I was administered fluticasone nasal spray (200 μg in each nostril) once a day, Group II was administered fluticasone nasal spray (200 μg in each nostril) plus cetrizine (10 mg) orally once a day and Group III was administered fluticasone nasal spray (200 μg in each nostril) plus montelukast (10 mg) orally once a day. Efficacy was measured based on daytime and nighttime symptom scores. Safety was evaluated on the basis of psychomotor tests, laboratory investigations and subjective assessment. The present study showed that montelukast add-on therapy is as efficacious as conventional therapies in controlling total symptom score, but it is more efficacious in controlling nighttime symptoms. Furthermore, montelukast add-on therapy does not cause psychomotor impairment as observed with cetrizine.
The goal of this study was to quantify in the dog the error that is made in assessing drug tissue concentrations when no correction for blood contamination is performed and hence to determine in which organs such a correction should be made. The organs investigated were the heart, the brain, the liver and the skeletal muscle, and the test drug used was the H1-antihistamine, cetirizine (0.1 or 0.6 mg/kg/day for 3 days, orally, n = 6 dogs). Radiolabelled serum albumin was used to quantitate blood trapped in the tissues. Blood and tissue samplings were performed 2 h after the last drug administration. Mean (+/-SEM) volumes of blood trapped in the liver, heart, muscle and brain were 263 +/- 12, 91 +/- 3, 27 +/- 1 and 20 +/- 2 microL/g, respectively. Apparent tissue/blood concentration ratios of cetirizine were 2.39 +/- 0.33, 1.11 +/- 0.09, 0.77 +/- 0.07 and 0.37 +/- 0.05 in the four organs. When correction for residual blood is not performed, cetirizine concentrations are underestimated (-13.6 +/- 3.2%) in the liver, slightly overestimated (+4.7 +/- 1.5 to +6.3 +/- 2.8%) in the brain, and neither over nor underestimated in the heart and muscle. Simulation data over a wide range of theoretical drug tissue/blood concentration ratios indicate that in the dog: (a) for the liver, correction of apparent tissue concentration for residual blood should be performed when the drug tissue/blood concentration ratio achieved is <0.8 or >4, (b) for the heart, correction should be made when this ratio is < or =0.4 and (c) for the brain and muscle, no correction is necessary unless the ratio is < or =0.1.
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Lupus enteritis, female gender, and positive anti-dsDNA antibody are risk factors for lupus cystitis. Japanese cases showed older age, a higher prevalence of vomiting and a lower prevalence of CNS involvement. We also report the efficacy of the novel use of cetirizine hydrochloride for lupus cystitis refractory to corticosteroid.
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Cetirizine 10 mg once daily was equivalent to hydroxyzine 25 mg tid in controlling the symptoms of patients with chronic urticaria, as assessed by patient and investigator evaluations.
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The Urticaria Patient Daily Diary, including the Urticaria Activity Score, has recently been validated in adults with chronic idiopathic urticaria (CIU), but its validity in adolescents is unknown. This study was designed to (1) assess the content validity of the Adolescent Urticaria Patient Daily Diary and, (2) collect exploratory data on symptom experiences, sleep interference, and health-related quality of life (HRQOL) of adolescents with CIU. The Urticaria Patient Daily Diary was modified to increase its relevance with an adolescent population. A qualitative, cross-sectional, multicenter study was then conducted in the United States so that adolescent subjects could provide information on the impact of urticaria on their lives and comment on the diary. Data were collected via in-person semistructured interviews with subjects 12-17 years of age with moderate-to-severe CIU. The most bothersome symptom was itching (44%). The impact of CIU on HRQOL varied. The majority of subjects (78%) reported waking up at least once a night. Overall, subjects found the diary to be clear, easy to comprehend, and easy to complete. Revisions were made to the diary based on feedback from subjects. After nine interviews, no new information was received. The symptoms of CIU are bothersome to adolescents, particularly itch, and urticaria has a negative impact on the sleep of adolescent patients. The final Adolescent Urticaria Patient Daily Diary has evidence of content validity in patients with CIU ranging from 12 to 17 years of age.
Fexofenadine and cetirizine have comparable onset of action times and similar frequencies of inhibition, as evaluated by the occurrence of 95% inhibition of histamine-induced wheal and flare.
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Data from 54 subjects on olopatadine and 51 on levocetirizine were analyzed for effectiveness. UAS and TSS values declined significantly with both drugs over the treatment period but the reduction was greater with olopatadine. Adverse event profiles were comparable with sedation being the commonest complaint.
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Levocetirizine and desloratadine are newer antihistamines indicated for the treatment of allergic rhinitis and chronic idiopathic urticaria.
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The pharmacologic activity and potency of the two enantiomers of cetirizine in the management of allergic skin conditions were investigated by studying the effect of treatment with 5.0 mg cetirizine; 2.5 mg levocetirizine, the (R)-enantiomer; and 2.5 mg ucb 28557, the (S)-enantiomer, on histamine-induced wheal and flare response in 18 healthy volunteers. Each treatment was administered as a single oral dose in randomized, double-blind, and crossover manner, and the efficacy of treatment was assessed over a period of 32 h, as per cent inhibition of the histamine-induced wheal and flare areas before treatment. Blood and urine samples were collected in a time-dependent manner and analyzed for the total amounts of each study drug, to elucidate their pharmacokinetic profiles.
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To study the NMR phenomena of cetirizine hydrochloride and assign all proton and carbon signals in NMR spectra.
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There were no significant age or sex differences between the AR and control groups. Pretreatment PSQI and actigraphy scores were worse in the AR group vs the control group. After treatment, sleep quality improved, and there were no differences in actigraphy and PSQI scores between the 2 groups. Before treatment, the T4SS was significantly correlated with the sleep efficiency, daytime napping episodes, and total nap duration variables of actigraphy (r = -0.53, P = .004; r = 0.43, P = .02; and r = 0.39, P = .04, respectively). The T4SS was correlated with the total PSQI score (r = 0.67, P < .001).
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In a randomized, double-blind, placebo-controlled trial, patients with psoriasis with a Psoriasis Area and Severity Index ≥ 10 starting an FAE up to a dose of dimethylfumarate 720 mg per day were randomized 1 : 1 to receive either additional cetirizine 10 mg once daily (n = 25) or placebo (n = 25) for 12 weeks. Randomization and treatment allocation were done at our hospital trial pharmacy. Primary outcomes were the incidence of adverse events and the proportion of patients discontinuing treatment.
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The effects of two selective H1 receptor blockers, cetirizine and loratadine, in comparison with placebo, on basophil histamine release and the bronchial response to histamine were assessed. The studies were performed in a group of 18 patients with pollinosis and 22 with atopic asthma. Both tests were performed before and after medication. Histamine release from isolated basophils was evaluated by Shore's method using anti-IgE and pollen antigen as stimulants. The bronchial provocation tests were performed by Ryan's method. The results were expressed as PC20FEV1. It was shown that both drugs significantly inhibited basophil histamine release induced by anti-igE or specific allergen. It was also found that these drugs effectively reduced the bronchial response to histamine challenge. These findings confirm the beneficial clinical effect of a new generation of selective H1 blockers in the treatment of IgE-mediated allergic diseases, and also the possible role of these drugs in the therapy of atopic asthma.
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A questionnaire was distributed Canada-wide to allergists, dermatologists, and a selection of practitioners with an interest in alternative medicine. The survey included questions on demographics, epidemiology, causative factors, diagnostic methods, therapeutic strategies, follow-up advice, and efficacy of therapies, with emphasis on personal experience.
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The study drugs shown significant different dynamics of skin reaction inhibition vs baseline and placebo. There were observed strongest effect after levocetirizine and cetirizine and next order after fexofenadine, desloratadine and loratadine.
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Seventy patients with CsU were enrolled. Parameters assessed included: (i) mean number of wheals (MNW); (ii) pruritus; (iii) mean total symptom score (MTSS); (iv) size of wheal; (v) interference of wheals with sleep; and (vi) sedation. Patients with CsU were divided randomly into two groups. Routine investigations were performed at baseline and at the end of the study.
Olopathadine, a newly developed histamine H1-receptor antagonist, was compared with cetirizine in its suppressive effects on histamine-induced wheal and flare reaction using an iontophoresis technique in a double-blind, crossover, placebo-controlled fashion. As a result, olopathadine was found to have effects comparable to cetirizine. This finding may predict the efficacy of this new H1-antagonist in treating pruritic skin diseases.
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Both active medications were significantly more effective than placebo and had a comparable onset of action in alleviating the symptoms of seasonal allergic rhinitis. The efficacy of both active drugs was comparable for the first 4 h after administration of the drugs on day 1 and day 2. However from 22 to 24 h after the first dose cetirizine was significantly superior to fexofenadine for the major symptom complex score and for sneezing. Concerning the total symptom complex score at day 2 fexofenadine could not reach superiority to placebo. No serious adverse events were reported.
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One hundred thirteen children aged 5 to 14 years (mean age, 7.7 years) with hay fever limited to grass pollen and no other clinically important allergies were randomized in an open study involving 6 Italian pediatric allergy centers to receive specific SLIT for 3 years or standard symptomatic therapy. All of the subjects had hay fever symptoms, but at the time of study entry, none reported seasonal asthma with more than 3 episodes per season. Symptomatic treatment was limited to cetirizine, loratadine, nasal budesonide, and salbutamol on demand. The hay fever and asthma symptoms were quantified clinically.
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Intrigued by the report demonstrating an increase in brain histamine levels by ethanol administration and central histamine transmission to affect the anxiety related behaviors, the present study examined the permissive role of central histaminergic transmission in the acute anxiolytic-like effect of the ethanol on elevated plus maze (EPM) in mice. Results demonstrated that prior administration of the agents that are known to enhance the brain histamine transmission, i.e. low dose of histamine (0.1μg/mouse, i.c.v.) or histamine precursor, l-histidine (500, 1000mg/kg, i.p.) or low dose of histamine releasing agent (H3 receptor inverse agonist), thioperamide (2μg/mouse) attenuated the acute anitanxiety-like effect of ethanol (2g/kg, i.p, 8% w/v) in mice on EPM. However, pre-treatment with the H1 receptor antagonist, cetirizine (0.1μg/mouse, i.c.v.) or H2 receptor antagonist, ranitidine (50μg/mouse, i.c.v.) failed to affect the attenuating effect of low dose of histamine on ethanol induced anxiolysis. On the other hand, only H1 receptor antagonist, cetirizine (0.1μg/mouse, i.c.v.) was able to partially reverse the attenuation of ethanol induced anxiolysis by l-histidine (1000mg/kg, i.p.). Surprisingly, in mice pre-treated with the higher dose of histamine (50μg/mouse, i.c.v.) or thioperamide (10μg/mouse, i.c.v.), the ethanol (2g/kg, i.p.) induced antianxiety-like effect was further enhanced on EPM. Furthermore, this potentiating effect of high dose of histamine on the ethanol (2g/kg, i.p.) was exacerbated on pre-treatment with the H1 receptor antagonist, cetirizine, while H2 receptor antagonist, ranitidine completely reversed this action of high dose of histamine on ethanol. Supportive to these results, i.c.v. pre-treatment with H1 receptor agonist, FMPH (2, 6.5μg/mouse, i.c.v.) attenuated while H2 receptor agonist, amthamine (0.1, 0.5μg/mouse, i.c.v.) enhanced the ethanol induced anxiolysis in mice. Thus, it is reasonable to contemplate that central histaminergic transmission functions to negatively modulate the acute ethanol-induced anxiolysis probably via stimulation of postsynaptic H1 receptor and histamine might contribute to the anxiolytic action of ethanol via H2 receptor activation.
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A cDNA clone for the human histamine H1 receptor was isolated from a lung cDNA library and stably expressed in CHO cells. The recombinant receptor protein present in the cell membranes, displayed the functional and binding characteristics of histamine H1 receptors. Mutation of Ser155 to Ala in the fourth transmembrane domain did not significantly change the affinity of the receptor for histamine and H1 antagonists. However, mutation of the fifth transmembrane Asn198 to Ala resulted in a dramatic decrease of the affinity for histamine binding, and for the histamine-induced polyphosphoinositides breakdown, whereas the affinity towards antagonists was not significantly modified. In addition, mutation of another fifth transmembrane amino acid, Thr194 to Ala also diminished, but to a lesser extent, the affinity for histamine. These data led us to propose a molecular model for histamine interaction with the human H1 receptor. In this model, the amide moiety of Asn198 and the hydroxyl group of Thr194 are involved in hydrogen bonding with the nitrogen atoms of the imidazole ring of histamine. Moreover, mutation of Thr194 to Ala demonstrated that this residue is responsible for the discrimination between enantiomers of cetirizine.