To investigate the relationship between single nucleotide polymorphisms (SNPs) of CACNA1C (SNPs rs58619945, rs7316246 and rs216008) and susceptibility of chronic spontaneous urticaria (CSU) as well as the curative effect of non-sedating antihistamine drugs.
 Methods: Peripheral blood were extracted from 191 CSU patients to collect DNA. Urticaria Activity Score 7 (UAS7) and Dermatology Life Quality Index (DLQI) changes were collected from these patients with different non-sedating antihistamine drugs. PubMed retrieval system was used to select the 3 SNPs (rs58619945, rs7316246 and rs216008) of CACNA1C. Susceptibility of CSU and curative effect of non-sedating antihistamine drugs (desloratadine, mizolastine, fisofenadine) in 189 CSU patients and 105 controls with different SNPs were compared with Chi-squared test. Data of 105 southern Chinese controls were extracted from the 1 000 genome database.
 Results: Frequency of rs58619945 G allele in the CSU patients was significantly higher than that in the controls [OR(95%CI)=0.660(0.470-0.925), P=0.016]. However, there was no significant differences in rs7316246 and rs216008 between the CSU patients and the controls. Meanwhile there was no significant difference in general curative effect of the 3 drugs in the 3 SNPs (rs58619945: OR=0.843, P=0.454; rs7316246: OR=2.103, P=0.102; rs216008: OR=0.237, P=0.363). There was significant difference in different alleles of rs216008 in the patients administered by desloratadine [OR(95%CI)=0.480(0.247-0.933), P=0.029]. No difference was shown in the 3 SNPs in patients administered by mizolastine.
 Conclusion: The rs58619945 A/G might be related to susceptibility of CSU, and the rs216008 mutation might affect drug response of desloratadine.
Calcium Channels, L-Type ; genetics ; Chronic Disease ; Genetic Predisposition to Disease ; Histamine H1 Antagonists, Non-Sedating ; therapeutic use ; Humans ; Loratadine ; analogs & derivatives ; therapeutic use ; Polymorphism, Single Nucleotide ; Prognosis ; Retrospective Studies ; Urticaria ; drug therapy ; genetics

Levocetirizine is a second-generation nonsedative antihistaminic agent that has been demonstrated to be safe and effective for treating allergic disease. There was only one case report of levocetirizine-induced liver toxicity, but a liver biopsy was not performed. In this article, we present the first case of levocetirizine-induced liver injury with histologic findings. A 48-year-old man was hospitalized with jaundice and generalized pruritus that had developed after 2 months of therapy with levocetirizine for prurigo nodularis. Laboratory findings revealed acute hepatitis with cholestasis. A liver biopsy demonstrated portal inflammation and hepatitis with apoptotic hepatocytes. The patient fully recovered 3 weeks after withdrawing levocetirizine. Although levocetirizine is safe and effective, physicians should be aware of its potential hepatotoxicity.
Cetirizine/*adverse effects/therapeutic use ; Chemical and Drug Induced Liver Injury/*diagnosis/pathology ; Histamine H1 Antagonists, Non-Sedating/*adverse effects/therapeutic use ; Humans ; Hypersensitivity/drug therapy ; Jaundice/etiology ; Liver/pathology ; Male ; Middle Aged ; Pruritus/etiology

H1-antihistamines have been prescribed widely for the treatment of allergic diseases, such as rhinitis, atopic dermatitis, and urticaria besides common colds since the 1940s. H1-antihistamines are classified by chemical structures (akylamine, piperazine, piperidine, ethanolamine, ethylendiamine, and phenothiazine) or functionally by permeability through blood brain barrier (first or second generation). The first generation antihistamines have been prescribed up to now with several adverse effects such as central nervous system dysfunction, anticholinergic and antiserotonic action and cardiotoxicity with overdose. Hence second generation antihistamines are recommended for the treatment of allergic rhinitis and urticaria. Physicians should consider concomitant diseases or medications when prescribing first generation antihistamines.
Blood-Brain Barrier ; Central Nervous System ; Common Cold ; Dermatitis, Atopic ; Ethanolamine ; Histamine Antagonists ; Histamine H1 Antagonists, Non-Sedating ; Permeability ; Piperazines ; Piperidines ; Rhinitis ; Rhinitis, Allergic, Perennial ; Urticaria

OBJECTIVE: To compare the efficacy and safety of histamine H1 receptor antagonist loratadine with Leukotriene receptor antagonist Ibudilast in steroid resistant allergic rhinitis in a randomized controlled clinical trial. METHOD: Thirty-five cases were treated by Ibudilast, and 34 cases by loratadine. Score system was used to compare the therapeutic effect of these two drugs on clinical symptoms and signs. RESULT: Ibudilast shows a better curative effect than loratadine in the improvement of the total scores on clinical symptom and signs(P<0.05). Scores of symptoms and signs in Ibudilast group after 3, 7, 14 days decreased significantly by means of square analysis of single factor (P<0.01). No complication was observed. CONCLUSION Ibudilast can effectively alleviate the clinical symptoms and signs of steroid resistant allergic rhinitis with confirmed efficacy and safety, thus is recommended in steroid resistant allergic rhinitis. Increased doses or prolonged treatment of steroid is inappropriate.
Adolescent ; Adult ; Aged ; Anti-Allergic Agents ; therapeutic use ; Female ; Histamine H1 Antagonists, Non-Sedating ; therapeutic use ; Humans ; Leukotriene Antagonists ; therapeutic use ; Loratadine ; therapeutic use ; Male ; Middle Aged ; Pyridines ; therapeutic use ; Rhinitis, Allergic, Perennial ; drug therapy ; Rhinitis, Allergic, Seasonal ; drug therapy ; Steroids ; pharmacology ; Young Adult

To investigate the effect of cetirizine hydrochloride on the expression of neurokinin 1 receptor (NK-1R) and cytokines production induced by substance P (SP) in HaCaT cells (a human epidermal keratinocyte cell line) and dermal fibroblasts. The effect of cetirizine on the expression of NK-1R protein was detected by flow cytometry and Western blotting analysis. The modulation of cetirizine on the production of interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6 and IL-8 in HaCaT cells and fibroblasts was measured by ELISA. The results showed that cetirizine significantly inhibited the expression of NK-1R in HaCaT cells and fibroblasts. SP induced the production of IFN-gamma, IL-1beta and IL-8 in both cell types. Cetirizine 1-100 micromol x L(-1) inhibited SP-induced IL-1beta and IL-8 production in HaCaT cells and fibroblasts, while had no effect on the production of IFN-gamma in both cells. Both SP and cetirizine had no effect on the secretion of IL-6 in HaCaT cells and fibroblasts. These findings suggest that cetirizine may be involved in the treatment of SP-induced skin inflammation by inhibiting the expression of substance P receptor and regulation the production of IL-1beta and IL-8 in epidermal keratinocyte and dermal fibroblasts.
Anti-Allergic Agents ; pharmacology ; Cell Line ; Cetirizine ; pharmacology ; Fibroblasts ; cytology ; metabolism ; Histamine H1 Antagonists, Non-Sedating ; pharmacology ; Humans ; Interferon-gamma ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-8 ; metabolism ; Keratinocytes ; cytology ; metabolism ; Receptors, Neurokinin-1 ; metabolism ; Substance P ; pharmacology

OBJECTIVE: To evaluate cardiovascular safety of loratadine, a second generation H1-antagonist, in treatment of patients with allergic rhinitis. METHOD: A total of 50 patients with persistent allergic rhinitis were enrolled, of which 19 cases (38.0%) had a history of cardiovascular diseases and/or presented abnormal electrocardiogram (ECG) findings without prolonged QT-interval. For all patents, 10 mg loratadine tablet was oral administrated once-daily for 30 days. ECG examinations were carried out both before and after treatment. Cardiovascular effects of loratadine were determined by the comparison of two ECGs. RESULT: All patients had no alterations in sinus rhythm after administration of loratadine for 30 days. There were no significant differences of heart rates, P durations, PR or QRS intervals between the baseline and end-point ECGs (P > 0.05), as well as no significant prolongation of the QT or QTc corrected for heart rate using Bazett' formula (P > 0.05). CONCLUSION Cardiovascular safety of loratadine, a second generation H1-antagonist, is confirmed in long-term treatment of persistent allergic rhinitis at a recommended dose.
Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Female ; Heart Rate ; Histamine H1 Antagonists, Non-Sedating ; administration & dosage ; adverse effects ; therapeutic use ; Humans ; Loratadine ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Rhinitis, Allergic, Seasonal ; drug therapy ; physiopathology ; Young Adult

OBJECTIVE: To assess the effect of desloratadine on quality of life (QOL) in patients with seasonal allergic rhinitis. METHOD: A randomized, double-blind, placebo-controlled study was designed on fifty patients with seasonal allergic rhinitis. The patients were randomly divided into three groups: A group: taking desloratadine by mouth and taking spraying of normal sodium; B group: placebo group, taking placebo by mouth and taking spraying of normal sodium; C group: taking desloratadine by mouth and taking spraying of Nasonex. Rhinitis quality of life (RQOL) questionnaire was used to evaluate QOL of patients with seasonal allergic rhinitis. The method of taking tabella was one tablet, one time a day; the method of taking spraying was one spray each nostril, once a day. The investigation lasted for two weeks. The RQOL questionnaire was administered at the start of the treatment and after one and two weeks of treatment by the telephone follow-up investigation. RESULT: After 1 and 2 weeks of treatment, symptoms scores were significantly decreased in the A group and C group compared with the placebo group (P < 0.05). After 1 and 2 weeks of treatment by the methods of A and C, the QOL of patients with seasonal allergic rhinitis was significantly improved compared with placebo group (P < 0.05). There was no QOL improvement in the placebo group. CONCLUSION Desloratadine could decrease symptom scores and improve QOL in patients with seasonal allergic rhinitis. The RQOL questionnaire could help doctor to effectively evaluate QOL in patients with seasonal allergic rhinitis, because of its integrity and convenience.
Adolescent ; Adult ; Double-Blind Method ; Female ; Histamine H1 Antagonists, Non-Sedating ; therapeutic use ; Humans ; Loratadine ; analogs & derivatives ; therapeutic use ; Male ; Middle Aged ; Quality of Life ; Rhinitis, Allergic, Seasonal ; drug therapy ; Treatment Outcome ; Young Adult

OBJECTIVE: To investigate the efficacy and safety of Mizolastine in the treatment of perennial allergic rhinitis. METHOD: Multicentric random Double-blind parallel-controlled study was adopted, and compared with placebo and Cetirizine. Patients (n = 177) were grouped, seventy-two in Mizolastine group, sixty-nine in Cetirizine and thirty-six in placebo group. RESULT: In the seventh curative day symptomatic and sign marks in Mizolastine group and Cetirizine group were lower, but the mark in Mizolastine group reduced more than in Cetirizine group and placebo group. Mizolastine group is better than Cetirizine group in improvement of nasal obstruction and itching with Visual analogue scale. In the twenty first curative day reduction of symptomatic and sign marks in Mizolastine group was lower than Cetirizine group, but no statistic difference. There were 27 adverse events, no serious adverse events in 177 patients during experimental period. Most adverse events were headache and dryness in mouth and eyes. There were 10 cases adverse events in Mizolastine group, one case was related with experiment and four cases might be related with experiment. There were 14 cases adverse events in Cetirizine group, one case was related with experiment and four cases might be related with experiment. There were three cases adverse events in placebo group. CONCLUSION Generally speaking the efficacy of Mizolastine in treatment of perennial allergic rhinitis is better than Cetirizine, Bad events are less. It is safe.
Adolescent ; Adult ; Aged ; Benzimidazoles ; adverse effects ; therapeutic use ; Cetirizine ; therapeutic use ; Child ; Double-Blind Method ; Female ; Histamine H1 Antagonists, Non-Sedating ; adverse effects ; therapeutic use ; Humans ; Male ; Middle Aged ; Rhinitis, Allergic, Perennial ; drug therapy ; Treatment Outcome ; Young Adult

Allergic rhinitis is a common disease of childhood characterized by nasal, throat, and ocular itching, rhinorrhea, sneezing, nasal congestion. Those affected with allergic rhinitis often suffer from associated inflammatory conditions of the mucosa, such as allergic conjunctivitis, rhinosinusitis, asthma, otitis media with effusion, and other atopic conditions, such as eczema and food allergies. Allergic rhinitis must be diagnosed and treated properly to prevent complications and impaired quality of life. Despite a high prevalence, allergic rhinitis isoften undiagnosed and inadequately treated, especially in the pediatric population. The first step in treatment is environmental control when appropriate. It may be difficult to eliminate all offending allergens effectively to reduce symptoms, so medications are often required. Many different classes of medications are now available, and they have been shown to be effective and safe in a large number of well-designed, clinical trials. Antihistamines are effective in treating immediate symptoms of sneezing, pruritus, watery eyes, and rhinorrhea. Second generation antihistamines are the preferred antihistamines because of their superior side effect profile. Thus, decongestants are commonly used with oral antihistamines. Intranasal corticosteroids are the most effective therapy for allergic rhinitis. Leukotriene modifier may be as effective as antihistamines in treating allergic rhinitis symptoms. Cromolyn sodium is an option for mild disease when used prophylactically, and ipratropium bromide is effective when rhinorrhea is the predominant symptom. When avoidance measures and medications are not effective, specific immunotherapy is an effective alternative. Only immunotherapy results in sustained changes in the immune system. Because of improved understanding of the pathogenesis, new and better therapies may be forthcoming. The effective treatment of allergic rhinitis in children will reduce symptoms and will improve overall health and quality of life, making a happier, healthier child.
Adrenal Cortex Hormones ; Allergens ; Asthma ; Child ; Conjunctivitis, Allergic ; Cromolyn Sodium ; Diagnosis ; Eczema ; Estrogens, Conjugated (USP) ; Food Hypersensitivity ; Histamine Antagonists ; Histamine H1 Antagonists, Non-Sedating ; Humans ; Immune System ; Immunotherapy ; Ipratropium ; Mucous Membrane ; Nasal Decongestants ; Otitis Media with Effusion ; Pharynx ; Prevalence ; Pruritus ; Quality of Life ; Rhinitis* ; Sneezing

AIMTo study the intervention of cetirizine on monocyte chemoattractant protein-1 (MCP-1) in different cutaneous inflammation models.

METHODSHistamine and IFN-gamma stimulated dermal fibroblast cells and HaCaT cells to mimic cutaneous inflammation. Expression of MCP-1 was assessed by means of RT-PCR and ELISA.

RESULTSCompared with the control group of dermal fibroblast (DF) cells and HaCaT cells, MCP-1 mRNA was significantly upregulated by histamine (10 micromol x L(-1)) and IFN-gamma (20 ng x mL(-1)). The protein secretions of MCP-1 were increased 3.5 fold and 8.4 fold in DF cells, respectively. The similar tendency was observed in HaCaT cells. The enhancing effects of histamine and IFN-gamma on MCP-1 protein production were significantly inhibited by cetirizine (1 and 10 micromol x L(-1)) in DF and HaCaT cells.

CONCLUSIONCetirizine may exert the anti-inflammatory effect of skin via inhibiting MCP-1 expression.

Cell Line ; Cells, Cultured ; Cetirizine ; pharmacology ; Chemokine CCL2 ; biosynthesis ; genetics ; Dermatitis ; metabolism ; Dermis ; cytology ; Fibroblasts ; cytology ; metabolism ; Histamine ; pharmacology ; Histamine H1 Antagonists, Non-Sedating ; pharmacology ; Humans ; Interferon-gamma ; pharmacology ; Keratinocytes ; cytology ; metabolism ; RNA, Messenger ; biosynthesis ; genetics