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Serum albumin (SA) is the main transporter of drugs in mammalian blood plasma. Here, we report the first crystal structure of equine serum albumin (ESA) in complex with antihistamine drug cetirizine at a resolution of 2.1Å. Cetirizine is bound in two sites--a novel drug binding site (CBS1) and the fatty acid binding site 6 (CBS2). Both sites differ from those that have been proposed in multiple reports based on equilibrium dialysis and fluorescence studies for mammalian albumins as cetirizine binding sites. We show that the residues forming the binding pockets in ESA are highly conserved in human serum albumin (HSA), and suggest that binding of cetirizine to HSA will be similar. In support of that hypothesis, we show that the dissociation constants for cetirizine binding to CBS2 in ESA and HSA are identical using tryptophan fluorescence quenching. Presence of lysine and arginine residues that have been previously reported to undergo nonenzymatic glycosylation in CBS1 and CBS2 suggests that cetirizine transport in patients with diabetes could be altered. A review of all available SA structures from the PDB shows that in addition to the novel drug binding site we present here (CBS1), there are two pockets on SA capable of binding drugs that do not overlap with fatty acid binding sites and have not been discussed in published reviews.
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We constructed pseudo-ternary phase diagrams to obtain the area of water-in-oil (w/o) microemulsion formation, prepared cetirizine hydrochloride microemulsion, and evaluated its quality. The w/o microemulsion had been formulated using span80 as surfactant, alcohol as co-surfactant, and oleinic acid as oil. Pseudo-ternary phase diagrams were constructed to evaluate the phase behavior of the w/o microemulsion. The properties, including appearance, particle size, and stability, were determined. The stable w/o microemulsion could be prepared using span80/ alcohol/ oleinic acid/ water (1.2/ 4.8/ 2/ 2). The w/o microemulsion is a new carrier for hydrosoluble drugs, which are easy to prepare with consistent quality.
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Children treated with probiotic mixture achieved a significant improvement of symptoms (p < 0.005), and QoL ((p < 0.001). Placebo group had worsening of symptoms (p < 0.005) and QoL (p < 0.001). The use of rescue medications was overlapping in the two groups. The intergroup analysis showed that probiotic mixture was significantly superior than placebo for all parameters.
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The total effective rate in the treatment group and control group was 93.75% and 56.66% respectively with significance difference between them (P <0.01). After treatment, the level of serum IL-10 was significantly lower while that of IL-8 was significantly higher in the treatment group (2.96 +/- 1.66, 50.17 +/- 32.35) than that in the control group (4.77 +/- 2.99, 29.44 +/- 17.62) respectively (P < 0.01).
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Comparison of bilastine and cetirizine in inhibiting skin wheal and flare responses over 24 h.
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Etoricoxib was the most frequent cause of FDE in our study. Other NSAIDs, paracetamol and doxycycline remain common causes of FDE but we caution that antihistamines, such as cetirizine, should also be considered.
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Several studies have compared the cutaneous efficacy of cetirizine and loratadine and their onset of action. We assessed the nasal effect of these two antihistamines in a randomized, double-blind, crossover, placebo-controlled trial in order to compare objectively their efficacy and onset of action in the noses of patients with allergic rhinitis. Nasal challenge was performed by nebulization of increasing doubling doses of histamine (0, 0.04-1.28 mg/nostril) in 12 patients (eight men, four women, aged 22-39 years). Nasal airway resistance (NAR) was measured by posterior rhinomanometry either 1.5 h or 4 h after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline NAR was identical between all study days (2.60-2.88 cmH2O.l-1.s). One and a half hours after intake, the increase in NAR induced by histamine was significantly reduced by both cetirizine and loratadine in contrast to placebo. However, with cetirizine the nasal obstruction was significantly lower than with loratadine (P < 0.05). Four hours after intake, a similar inhibition of the nasal obstruction caused by histamine was observed with both cetirizine and loratadine (P < 0.05). In conclusion, this study found cetirizine and loratadine to have similar nasal efficacy at therapeutic dosage 4 h after intake, whereas cetirizine was more effective than loratadine 1.5 h after intake. In agreement with the results observed in the skin, our study suggests a more rapid onset of action of cetirizine in the nose in allergic rhinitis.
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The current study demonstrated that a Bifidobacteria mixture was able of significantly improving AR symptoms and QoL in children with pollen-induced AR and intermittent asthma.
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We have compared the pharmacodynamic activity of the two antihistamines at therapeutic dosages, cetirizine at 10 mg and fexofenadine at 120 mg and 180 mg, on histamine-induced skin reactivity during a 24-hour period after single intake.
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Allergic sensitisation of the airways occurs in the mucosa of the shock organ, or in the lymphatic stations draining these structures. The lymphatic structure closest to the nasal mucosa in humans is the adenoid. Pediatric adenoidal obstruction of the nasal airway is associated with significant morbidity and is a frequent indication for surgery. Because efficacious medical alternatives to adenoidectomy are lacking, we assessed the potency of standard-dose topical nasal fluticasone propionate and Cetirizine in reduction of adenoidal obstruction of the nasal airway. To examine the influence of these medicines on the adenoid hypertrophy (AH) we studied 43 children ages 4 to 9 years, who had AH and house dust mite allergy. Properly administered aqueous nasal fluticasone propionate and Cetirizine in standard doses can significantly reduce adenoidal hypertrophy and nasal airway obstructive symptoms in atopic children.
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A novel FVs based topical formulation of levocetirizine was successfully developed for treatment of atopic dermatitis.
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Data on the validated, standardized Behavior Screening Questionnaire were obtained prospectively from 35 to 53 months for 150 atopic children who had asthma by age 53 months and for 115 who did not.
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A total of 1,343 health plan enrollees who received an oral antihistamine prescription were continuously enrolled during the year 2000 and diagnosed with allergic rhinitis. Of these patients, 246 (18%) consented to a multiallergen- specific IgE test, and 159 patients (64.6%) had a negative IgE test result. A total of 163 patients were classified as frequent antihistamine users (3 or more antihistamine prescriptions), and 101 (62.0%) of these patients had negative test results. Our study demonstrated no relation between prescribed antihistamine use and patient sensitization status.
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In this 3-week randomized, double-blind, double-dummy multicenter, crossover study terfenadine, 120 mg, was compared with cetirizine, 10 mg, both given once daily in the treatment of perennial allergic rhinitis in sixty patients. Compared with the investigators' pretreatment assessment, both terfenadine and cetirizine significantly reduced the severity of all five symptoms (P less than .001). The two treatments were equally effective in controlling eye irritation, sneezing, nasal congestion and itchy nose, throat and palate, but cetirizine improved rhinorrhea more than terfenadine (P less than .05). Daily symptom assessments by the patients for the last 14 days of each treatment period showed no difference in efficacy between the two drugs for any of the symptoms. There were also no differences between the two drugs for overall assessments of efficacy or patient preference. Adverse events were recorded more frequently while taking cetirizine, with 14 attributable events compared with only five with terfenadine. Four of the cetirizine-related events were drowsiness or tiredness, but none was reported while patients were taking terfenadine. There was a tendency to increased weight (greater than 1 kg) with both treatments.
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A Caucasian woman in her late 20s was referred to the allergy/chest clinic by her general practitioner with an 8-month history of recurrent facial angio-oedema. She had no history of urticaria or airways symptoms and denied any similar problems previously. She had no family history of similar illness and was not on any regular medications. There was no history of atopy. Initially, a clinical diagnosis of idiopathic angio-oedema was made. Despite being treated with several antihistamines with doses equivalent to 40 mg of cetirizine/day, her problem had failed to respond satisfactorily. Later on, she also revealed history of intermittent gastrointestinal symptoms such as abdominal pain and diarrhoea. Routine investigations were unremarkable. The patient was referred to a dermatology clinic and a diagnosis of orofacial granulomatosis was suggested: a rare granulomatous disease presenting with lip enlargement, which may or may not be associated with Crohn's disease. A biopsy of the oral mucosa was consistent with this diagnosis.
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Overall, 683 SAR patients, aged 12-70 years, were randomized to a double-blind treatment with bilastine 20 mg, cetirizine 10 mg or placebo, once daily for 14 days, in 61 centres across Europe. Patients recorded reflective (over the past 12 h) and instantaneous nasal (obstruction, rhinorrhoea, itching and sneezing) and non-nasal (ocular tearing, redness and itching) symptom scores (NSS and NNSS, respectively) twice daily, according to a pre-determined severity scale to provide reflective and instantaneous total symptom scores (TSS). The primary efficacy measure was the area under curve (AUC) of reflective TSS over 14 days of treatment (TSS-AUC(0-14 days)). Secondary efficacy measures included mean change from baseline in TSS, NSS and NNSS; discomfort caused by AR; and investigator's clinical global impression of the treatment. Safety was assessed according to adverse events (AEs), laboratory tests and electrocardiograms.
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Allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) are common causes of substantial illness and disability in preschool children. Antihistamines are commonly used to treat preschool children with these conditions, but their use is based mostly on extrapolated efficacy from adult populations; it is thus important to characterize the safety of antihistamines in the pediatric population. This study was designed to assess the safety of levocetirizine dihydrochloride oral liquid drops in infants and children with AR or CIU. Two multicenter, double-blind, randomized, parallel-group studies randomized infants aged 6-11 months (study 1, n = 69) and children aged 1-5 years (study 2, n = 173) to levocetirizine, 1.25 mg (q.d. or b.i.d., respectively), or placebo for 2 weeks, using a 2:1 ratio. Safety evaluations included treatment-emergent adverse events (TEAEs), vital signs, electrocardiographic (ECG) assessments, and laboratory tests. The overall incidence of TEAEs was similar between levocetirizine and placebo in both studies. Most TEAEs were mild or moderate in intensity. TEAEs prompted discontinuation of therapy in three patients receiving levocetirizine in study 1. No clinically relevant changes from baseline in vital signs or laboratory parameters were apparent in either study; changes from baseline in these evaluations were similar between groups. No significant changes were observed in ECG parameters, including corrected QT interval. Levocetirizine, 1.25 and 2.5 mg/day, was well tolerated in infants aged 6-11 months and in children aged 1-5 years, respectively, with AR or CIU.
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Patch testing with hydroxyzine 1% and 10% in petrolatum (Chemotechnique), and with powdered Zyrtec (cetirizine) and Xyzal (levocetirizine) pills, prepared at 20% in water and at 20% in petrolatum, was performed in both residual lesions and healthy skin.
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Nasal obstruction is the main symptom in patients with persistent allergic rhinitis. Some antihistamines have been demonstrated to be capable of improving this symptom. The aim of this pilot study was to evaluate nasal symptoms, nasal airflow, and decongestent activity in patients with persistent allergic rhinitis, before and after treatment with levocetirizine or placebo.
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The aim of the study was to monitor the safety of levocetirizine prescribed in the primary care setting in England, in the immediate postmarketing period.
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For the literature search, published reports on lupus cystitis were searched by MEDLINE and ICHUSHI WEB. The inclusion criterion was interstitial cystitis, fulfilling the SLE classification criteria of American College of Rheumatology in 1997 and with either hydronephrosis detected by image studies (either computed tomography or ultrasonography) or bladder histopathology consistent with lupus cystitis. Interstitial cystitis without the fulfillment of the classification criteria was excluded. Patient demographic data and clinical data were retrieved from the literature and analyzed.
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The neutral form of hydroxyzine interacted mainly via hydrophobic interactions with the bilayer lipid core of the membrane, whereas for the cationic form both hydrophobic and electrostatic interactions were involved. Zwitterionic and anionic cetirizine were less lipophilic than its cation, which behaved like the corresponding species of hydroxyzine. Zwitterionic cetirizine interacted more by weak electrostatic interactions with the polar headgroups of phospholipids than by hydrophobic interactions with the membrane interior. The lipophilicity of its anion reflected the balance of repulsive electrostatic interactions between the carboxylate and phosphate groups and the hydrophobic interactions with the lipid core.
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We investigated the effect of betotastine besilate (betotastine) on the experimental allergic rhinitis. The oral administration of betotastine (1, 3 and 10 mg/kg) inhibited the increase in dye leakage during and after the nasal perfusion of antigen in actively sensitized rats. It also prevented the increase in intranasal pressure induced by topically applied histamine in non-sensitized guinea pigs. Cetirizine and terfenadine dose-dependently inhibited the increase in a similar manner. Ketotifen (0.01-0.3 mg/kg, p.o.) inhibited the increase more than 50% at 0.01 mg/kg. The ID50s of ketotifen, cetirizine, betotastine and terfenadine for this model were more than 0.01 mg/kg, 0.01 mg/kg, 0.03 mg/kg and 0.5 mg/kg, respectively. Furthermore, in actively sensitized guinea pigs, nasal airway resistance showed a biphasic increase after the topical antigen challenge to the nasal cavity; the first peak at 0.5 hr and a second peak at 4 hr. Both the responses of first and second peaks were significantly inhibited by orally administered betotastine besilate, and its inhibitory effect on the second peak was the strongest among drugs tested. Since betotastine showed significantly inhibitory effects in experimental allergic rhinitis models, it was suggested to show a good efficacy for the treatment of allergic rhinitis clinically.
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These results suggest that cetirizine exerts its anti-inflammatory effects by inhibiting MIF as well as IL-8 production, such as those involved in inflammatory allergic skin disease, suggesting a broad spectrum of action beyond its mere H1-receptor-antagonistic function.