The prophylactic effectiveness of the new, second-generation antihistamines cetirizine and terfenadine was evaluated in a double-blind, multicenter study of 487 patients with seasonal allergic rhinitis. The patients were randomly assigned to eight weeks of treatment with 10 mg of cetirizine given either in the morning or evening, or 60 mg of terfenadine twice daily. Success rates in the three treatment groups, as assessed by physicians, were 61%, 58%, and 56%, respectively. On a scale of 0 (no symptoms) to 100 (most severe symptoms), symptoms in the three regimens were rated by patients as 31, 34, and 41, respectively. A significantly greater alleviation of eye watering and irritation was noted in the morning cetirizine group than in the terfenadine group. No serious side effects were experienced. It is concluded that 10 mg of cetirizine once daily is as effective as 60 mg of terfenadine twice daily in the prophylactic treatment of seasonal allergic rhinitis.
Allergic rhinitis (AR) and asthma share common mediators, cytokines, and chemokines from mast cells and basophils that are central to the complex cascade of events involved in the inflammatory response. Histamine is the salient mediator released after immunologic challenge, initiating multiple pathologic processes of the allergic reaction that result in bronchial smooth muscle contraction, vasodilation, mucus hypersecretion, and edema. The recent identification of a fourth histamine receptor has reinforced clinical interest in the pleiotropic effects of histamine and the relative roles of histamine receptors in mediating immune and inflammatory responses.
Adult guinea pig ventricular myocytes were isolated by enzymatic digestion. Cells were continuously perfused with Tyrode's solution at 33-35 degrees C. Recordings were made using the whole-cell, patch clamp technique. Action potentials (APs) were elicited under current clamp. Voltage clamp was used to study the effect of drugs on I(Kr) (rapidly activating delayed rectifier potassium current), I(Na) (sodium current), and I(Ca) (L-type calcium current). Dofetilide increased the myocyte action potential duration (APD) in a concentration-dependent manner, with a pIC50 of 7.3. Dofetilide 1 microM elicited early afterdepolarizations (EADs) but had little affect on I(Ca) or I(Na). E-4031 increased APD in a concentration-dependent manner, with a pIC50 of 7.2. In contrast, 10 microM loratadine, desloratadine, and cetirizine had little effect on APD or I(Kr). Interestingly, cisapride displayed a biphasic effect on myocyte APD and inhibited I(Ca) at 1 microM. Even at this high concentration, cisapride did not elicit EADs. A number of AstraZeneca compounds were tested on cardiac myocytes, revealing a mixture of drug actions that were not observed in hERG currents in HEK293 cells. One compound, particularly AR-C0X, was a potent blocker of myocyte AP (pIC50 of 8.4). AR-C0X also elicited EADs in cardiac myocytes. The potencies of the same set of drugs on the cloned hERG channel also were assessed. The pIC50 values for dofetilide, E-4031, terfenadine, loratadine, desloratadine, and cetirizine were 6.8, 7.1, 7.3, 5.1, 5.2, and <4, respectively. Elevation of temperature from 22 to 35 degrees C significantly enhanced the current kinetics and amplitudes of hERG currents and resulted in approximately fivefold increase in E-4031 potency.
Histamine concentrations in the microdialysis fibre outflow with 3 and 10 mg/ml codeine were maximal at 2-4 min when 910 +/- 156 and 1194 +/- 304 nM respectively were found in the placebo group. Cetirizine and loratadine did not modify either the kinetics or total histamine release while significantly (p < 0.01) inhibiting weal and flare responses.
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Persistent allergic rhinitis often impairs quality of life.
Allergic rhinitis (AR) and allergic asthma are caused by an IgE-mediated inflammatory reaction. Probiotics may exert anti-inflammatory and immune-modulatory activity. Thus, this study aimed at investigating whether a Bifidobacteria mixture could be able to relieve nasal symptoms, and affect quality of life (QoL) in children with AR and intermittent asthma due to Parietaria allergy.
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Observational reports have linked vitamin D with chronic urticaria, yet no randomized controlled trial has been conducted.
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Cetirizine orodispersible tablets were prepared to achieve quick onset of action and for maximum bioavailability. Tablets were prepared using cetirizine along with camphor and mannitol in the proportion of 1:1:1, 1:1:3, and 1:1:6. The flow property of granules was found to be good for the formulation CZ2 (1:1:3). The hardness and friability of all the formulations were found to be within the standard limit for orodispersible tablets. Disintegration time was found to be rapid in formulation CZ2 (1:1:3).The in vitro dissolution time was found to be 100% in 11 minutes for the formulation CZ2 (1:1:3).
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Moxibustion at "heat sensitive points" is an ideal therapy for perennial allergic rhinitis with low recurrence rate.
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Histamine and serotonin were iontophoretically applied in 10 healthy volunteers. Wheals and flares were planimetrically evaluated. Itching and burning sensations were entered on a scale over 24 min. The examination also comprised alloknesis, elicitation of perifocal itch sensation by usually non-itching (e.g. mechanical) stimuli.
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The recommended drug for moderate to severe chronic rhinitis is intranasal steroids (INS). However, nasal congestion could be refractory and need additional treatments.
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Data regarding narrowband ultraviolet B (NB-UVB) phototherapy in patients with chronic urticaria is limited. The aim of this open, controlled study was to determine whether NB-UVB is effective in treating urticaria in combination with antihistamin. A total of 81 patients with chronic urticaria were recruited, 48 of whom were randomized into the NB-UVB plus antihistamine group. The control group (n = 33) received only antihistamine. Patients were assessed using the urticaria activity score and a visual analogue score (VAS). The 2 groups were evaluated at the same time-points: at treatment sessions 10 and 20 and at follow-up 3 months post-treatment. The reduction in urticaria activity score and VAS was statistically significant (p < 0.05 for both groups). When comparing the groups, the mean urticaria activity score was significantly lower in the NB-UVB group at session 10 (22.6 vs. 27.3) and session 20 (17.4 vs. 20.7). Statistically significant differences were also noted in VAS between the 2 groups (p < 0.01) at 3 months post-treatment. We conclude that NB-UVB may be an effective complementary treatment for patients with chronic urticaria.
Mastocytosis refers to a rare collection of disorders, both cutaneous and systemic, that are characterized by increased numbers of mast cells. Depending on the extent of the disease, these disorders may present with symptoms resulting from mast cell degranulation including flushing, diarrhea, vomiting, cramping, syncope, or anaphylaxis. In pediatric patients, cutaneous involvement is most prevalent in the form of urticaria pigmentosa, which is typically asymptomatic or minimally so with resolution by adolescence. In this case report and review of literature, we review a case of a 3-year-old child with uritcaria pigmentosa displaying recurrent syncope and anaphylaxis as the first presentation of systemic mastocytosis. We found data to be limited on this topic, and concluded that pediatric patients with prior diagnoses of cutaneous mastocytosis could benefit from either more aggressive screening for systemic disease or prophylactic treatment with antihistamines and rescue subcutaneous epinephrine.
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AAG has favorite effect for treatment of chronic urticaria, its regulation on serum levels of RANTES, Eotaxin and TNF-alpha may be the mechanism of action.
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This was a meta-analysis of original reports from randomized, double-blind, placebo-controlled studies. Clinical studies without detailed reports, open-label, non-randomized and non-controlled studies, or paediatric studies, were excluded. Study subjects were divided into an environmental exposure (EE) group or a natural exposure (NE) group.
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In this study, the efficacy of single oral dosages of 5 and 10 mg desloratadine and levocetirizine were compared by using histamine-induced wheal and flare reactions.
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This study mainly focuses on taste masking of CTZ by inclusion complexation method, its formulation development in the MCG form and its quality and performance evaluation with the study of potential factors affecting drug release by 3(2) full factorial experimental design. A "chew out" study is carried out to assess in vivo drug release from MCG, in which residual amount is extracted from the chewed sample.
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1. The intraperitoneal (i.p.) injection of 1 or 10 micrograms ovalbumin to sensitized Balb/c mice led to an acute histamine release, firstly evidenced 1 min after the challenge and returning to basal levels 30 min thereafter. This phenomenon was unaccompanied by protein extravasation. A dose-dependent increase in the amounts of immunoreactive leukotriene (LT) C4 and LTB4 was observed in the peritoneal washing from sensitized mice 6 h after 1 or 10 micrograms ovalbumin administration. In separate experiments, the i.p. administration of 1 mg activated zymosan to non-immunized mice was followed by a marked protein extravasation, and by immunoreactive LTC4 and LTB4, but not histamine, release in mouse peritoneum 1 h after its injection. 2. Mediator release in the mice peritoneal cavity was concomitant with a transient neutrophil infiltration, which peaked at 6 h and returned to basal levels therefore. An intense eosinophil accumulation starting at 24 h, peaking at 48 h and returning to basal values at 164 h, was also observed. 3. Ovalbumin (1 microgram)-induced eosinophilia, observed at 24 h, was reduced by the pretreatment of the animals with dexamethasone (1 mg kg-1, s.c.) or with the 5-lipoxygenase inhibitor, BWA4C (20 mg kg-1, s.c.), whereas indomethacin (2 mg kg-1, s.c.) and the platelet-activating factor (PAF)-antagonist SR 27417 (10 mg kg-1, s.c.) were ineffective. These results indicate that metabolites of arachidonic acid of lipoxygenase pathway, but not cyclo-oxygenase derivatives or PAF, mediate antigen-induced eosinophil accumulation in the mouse peritoneum. 4. The histamine HI receptor antagonist drug, cetirizine (15-30 mg kg-1, s.c.) markedly reduced ovalbumin-induced eosinophil accumulation under conditions where terfenadine was ineffective, suggesting that the effect of cetirizine was not related to the inhibition of the H1 receptor effects of histamine.5. The immunosuppressive agent, FK-506 (1-2 mg kg-1, s.c.) and the protein synthesis inhibitor,cylcoheximide, when administered either in situ (0.06 ng/cavity) or systemically (5 mg kg-1, s.c.),prevented antigen-induced eosinophil accumulation in the mouse peritoneum, contributing to the concept that substances (probably cytokines) originating from lymphocytes may be involved in the modulation of the eosinophilotactic response in this model.6. The results of the present study indicate that the i.p. administration of ovalbumin to actively sensitized mice induced late eosinophil accumulation in the peritoneal cavity. This phenomenon, which may be in part mediated by the release of lipoxygenase metabolites and/or by newly generated factors,such as T-lymphocytes-derived eosinophilotactic cytokines, offers an interesting tool to investigate the mechanism of action of anti-allergic and anti-inflammatory drugs.
Ebastine (CAS 90729-43-4), cetirizine (CAS 83881-51-0) and loratadine (CAS 79794-75-5) are second generation H1-antihistamines of proven efficacy for treating allergy. Recent clinical studies have found ebastine to be more effective than cetirizine or loratadine in alleviating the symptoms of seasonal allergic rhinitis. The objective of this study was to compare the efficacy of these compounds in three guinea-pig modeles of bronchoconstriction, elicited either by histamine, allergen or leukotriene C4 in order to shed light onto the mechanisms that might explain differences found in clinical studies. In the present experiments, ebastine and cetirizine were equipotent against aerosol histamine-induced bronchospasm in guinea pigs (ED50 115 and 100 micrograms/kg p.o., respectively), while loratadine was three-fold less potent. In the same model the effects of ebastine, loratadine and cetirizine lasted 21, 19 and 15 h, respectively. Ebastine (ED50 334 micrograms/kg p.o.) was the most potent compound in inhibiting allergen-induced bronchospasm in conscious guinea pigs. In vitro studies in tracheally perfused guinea pig lungs demonstrated that ebastine and loratadine inhibited with equal potency the bronchoconstriction induced by leukotriene C4 whilst cetirizine was significantly less potent. Finally, in another in vivo study, ebastine reverted the changes in pulmonary resistance induced by leukotriene C4 in anaesthetised guinea pigs, whereas cetirizine and loratadine were devoid of activity in this model. In accordance with the clinical data, ebastine proved to be the substance with the widest range of application in animal experiments, too.
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Patients with RVC refractory to standard antifungal therapy and a history of allergy may respond to the combination of antihistamine and antifungal therapy.
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All the antihistamines we examined suppressed the increase of CD86(+) cells after histamine stimulation in a dose-dependent fashion, and all H(1)-type antihistamines were more efficacious than cimetidine. IL-8 production stimulated with histamine was also suppressed by cetirizine, ketotifen, and olopatadine. Unexpectedly, the suppressive effect of these antihistamines on the CD86 augmentation was highly variable among different healthy control participants. Interestingly, in 10 of 13 cases of chronic urticaria, this in vitro analysis of antihistamines correlated with the clinical response to antihistamines.
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Medical, scientific and societal progress has been such that, in a universalist humanist perspective such as the WHO's, it has become an ethical imperative for the primary endpoints in evidence based health care research to be expressed in e.g. Quality Adjusted Life Years (QALYs). The classical endpoints of discrete health-related functions and duration of survival are increasingly perceived as unacceptably reductionistic. The major problem in 'felicitometrics' is the measurement of the 'quality' term in QALYs. That the mental, physical and social domains, each containing many dimensions and items, all contribute to QOL is uncontroversial. What is controversial, is the weight of the different dimensions in overall QOL. It has been shown to be very different between different patient populations. In human individuals, assuredly complex systems, the many dimensions and items of QOL observably interact, probably sometimes in chaotic ways. In these conditions, the weights of isolated items in individuals become for all practical purposes meaningless. Therefore, the much used multi-item questionnaires at best describe, but do not evaluate QOL, neither in individuals, nor in populations. For example, allergic patients treated with cetirizine scored better than those on placebo on all dimensions of the SF-36, a standard QOL questionnaire. Here there is no serious doubt that the treatment improved QOL, because it is highly unlikely that any important dimension on which the patient groups would have scored otherwise is missing in the SF-36. However, whether piracetam treatment of acute stroke, which improved the surrogate endpoints neurological and functional scores, also improved QOL is plausible, but will be proven only when comprehensive QOL measurement will have been done. And suppose in randomised populations of end-stage metastatic solid cancer patients, one would compare palliative last-line chemotherapy with only palliative care, and one would, as can be expected, find no significant differences in average survival, and chemotherapy superior for the mental domain, but inferior for the physical comfort domain: we would not know which treatment, on aggregate, would be the better. The problem is that QOL is an individual and emergent construct, the resultant of a great many interactions, and of a different order than its contributing components. Overall QOL can therefore best be captured only as the Gestalt of a global self-assessment. Just as people in everyday life, while acting under uncertainty, make global assessments all the time, so they can seriously answer the serious question: 'How have you been?' A solemn, practical, non peer-relativistic, non-cultural, experiential, and well tolerated way to obtain such responses is Anamnestic Comparative Self Assessment (ACSA), in which the subjects' memories of the best and the worst times in their life experience define their individual scale of QOL. ACSA is thus both exquisitely idiosyncratic, and yet can in a universalist humanistic perspective be considered generic. Using both a multi-item questionnaire and a global assessment allows by one logistic regression, to estimate the weights of the dimensions and items in populations, and thus identify those whose improvement would most contribute to the QOL of the greatest number. A combined approach to measurement of QOL is necessary to maximise the utility of QOL interventions.