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Background: A fexofenadine/pseudoephedrine combination tablet (F/P) is an optimal product for nasal obstruction. It contains fexofenadine hydrochloride, a histamine H1-receptor antagonist for sneezing and rhinorrhea and pseudoephedrine hydrochloride, an α-adrenergic agonist. The effect of an antihistamine-decongestant on nasal obstruction has been demonstrated in previous studies, but onset of action and efficacy data on nasal obstruction are limited., Objective: We estimated the efficacy of F/P on nasal obstruction in patients with house dust mite-induced allergic rhinitis (AR) versus fexofenadine (F) using objective methods., Methods: In this single-center, single-dose, prospective, randomized, parallel-group study, 24 adult patients with a history of at least 2 years of AR and nasal obstruction were randomized to receive F/P or F. The effect on nasal obstruction was evaluated using nasal airflow and visual analog scale (VAS) score measured at 30-minute intervals before and for 8 hours after dosing. The primary end point was onset of action, based on a comparison of absolute change from baseline in nasal airflow between F/P and F. The protocol was registered in a clinical trial registry as UMIN 000041845., Results: The onset of action for F/P was 30 minutes based on nasal airflow and 60 minutes based on VAS. F/P maintained a significant beneficial effect after onset of effect, while F showed no significant change during the test period., Conclusions: We found F/P had a clear effect on nasal obstruction associated with perennial AR when compared with F. There was a time lag in nasal airflow improvement and nasal obstruction relief.

To gain a comprehensive overview of the landscape of clinical trials for the H 1 -receptor antagonists (H 1 R antagonists) cetirizine, levocetirizine, loratadine, desloratadine, and fexofenadine and their potential use cases in drug repurposing (the use of well-known drugs outside the scope of the original medical indication), we analyzed trials from clincialtrials.gov using novel custom-coded software, which itself is also a key emphasis of this paper. To automate data acquisition from clincialtrials.gov via its API, data processing, and storage, we created custom software by leveraging a variety of open-source tools. Data were stored in a relational database and annotated facilitating a specially adapted web application. Through the data analysis, we identified use cases for repurposing and reviewed backgrounds and results in the scientific literature. Even though we found very few trials with published results for repurpose indications, extended literature research revealed some prominent use cases: Cetirizine seems promising in mitigating infusion-associated reactions and is also more effective than placebo in the treatment of androgenetic alopecia. Loratadine may be beneficial in the prophylaxis of G-CSF-related bone pain. In COVID-19, H 1 R antagonists may be helpful, but placebo-controlled scientific evidence is needed. For asthma, the effect of H 1 R antagonists only seems to be secondary by alleviating allergy symptoms. Our novel method to find potential use cases for repurposing of H 1 R antagonists allows for high automation, reduces human error, and was successful in revealing potential areas of interest. The software could be used for similar research questions and analyses in the future., (© 2023. The Author(s).)

Background: Recent evidence has suggested that oral antihistamines could have a beneficial role in atopic dermatitis (AD) because of their anti-inflammatory action., Aim: To evaluate the effectiveness of adding an oral second-generation, nonsedating, H1-receptor antihistamine (fexofenadine) to topical treatment in AD., Methods: In this prospective randomized study, 50 patients with a diagnosis of mild to moderate AD were recruited and randomized into two groups: Group A was given appropriate topical treatment (topical tacrolimus 0.03-0.1% ointment once daily along with topical fluticasone propionate 0.05% cream once daily, as well as paraffin-based emollients) combined with oral fexofenadine, while Group B was given appropriate topical treatment only. Both groups received the respective treatments for 8 weeks., Results: There was no significant difference between the two groups in terms of the SCORing Atopic Dermatitis and the 5-dimensions Itch Scale at any of the time points (Weeks 2, 4 and 8). However, in the fexofenadine group, the level of serum interleukin (IL)-31 decreased significantly from baseline to Week 8 of treatment., Conclusions: Although we could not conclusively confirm the clinical efficacy of adding oral fexofenadine to topical treatment in AD, serological evaluation indicates that fexofenadine treatment can lead to significant lowering of serum IL-31 levels in patients with AD., (© 2021 British Association of Dermatologists.)

Inflammatory Bowel Disease (IBD) is an autoimmune condition with complicated pathology and diverse clinical signs. TNFα is believed to play a crucial role in the pathogenesis of IBD. We recently identified fexofenadine, a well-known antagonist of histamine H1 receptor, as a novel inhibitor of TNFα signaling. Additionally, cytosolic phospholipase A2 (cPLA2) was isolated as a binding target of fexofenadine, and fexofenadine-mediated anti-TNF activity relied on cPLA2 in vitro. The objective of this study is to determine whether fexofenadine is therapeutic against chemically-induced murine IBD model and whether cPLA2 and/or histamine H1 receptor is important for fexofenadine's anti-inflammatory activity in vivo by leveraging various genetically modified mice and chemically induced murine IBD models. Both dextran sulfate sodium- and 2, 4, 6-trinitrobenzene sulfonic acid-induced murine IBD models revealed that orally delivered fexofenadine was therapeutic against IBD, evidenced by mitigated clinical symptoms, decreased secretions of the proinflammatory cytokine IL-6 and IL-1β, lowered intestinal inflammation, and reduced p-p65 and p-IĸBα. Intriguingly, Fexofenadine-mediated protective effects against IBD were lost in cPLA2 deficient mice but not in histamine H1 receptor-deficient mice. Collectively, these findings demonstrate the therapeutic effects of over-the-counter drug Fexofenadine in treating DSS-induced IBD murine and provide first in vivo evidence showing that cPLA2 is required for fexofenadine's therapeutic effects in murine IBD model and probably other inflammatory and autoimmune diseases as well.

Current drug therapies for cutaneous leishmaniasis are often difficult to administer and treatment failure is an increasingly common occurrence. The efficacy of anti-leishmanial therapy relies on a combination of anti-parasite activity of drugs and the patient's immune response. Previous studies have reported in vitro antimicrobial activity of histamine 1-receptor antagonists (H1RAs) against different pathogens. We used an ex vivo explant culture of lymph nodes from mice infected with Leishmania major to screen H1RAs compounds. Azelastine (AZ) and Fexofenadine (FX) showed remarkable ex vivo efficacy (EC50 = 0.05 and 1.50 μM respectively) and low in vitro cytotoxicity yielding a high therapeutic index. AZ significantly decreased the expression of H1R and the proinflammatory cytokine IL-1ẞ in the ex vivo system, which were shown to be augmented by histamine addition. The anti-leishmanial efficacy of AZ was enhanced in the presence of T cells from infected mice suggesting an immune-modulatory mechanism of parasite suppression. L. major infected BALB/c mice treated per os with FX or intralesionally with AZ showed a significant reduction of lesion size (FX = 69%; AZ = 52%). Furthermore, there was significant parasite suppression in the lesion (FX = 82%; AZ = 87%) and lymph nodes (FX = 81%; AZ = 36%) with no observable side effects. AZ and FX and potentially other H1RAs are good candidates for assessing efficacy in larger studies as monotherapies or in combination with current anti-leishmanial drugs to treat cutaneous leishmaniasis., Competing Interests: The authors have declared that no competing interests exist.

Nasal obstruction is one of the most bothersome symptoms of allergic rhinitis (AR) affecting sleep-related quality of life in AR patients. Although several treatments were tested to control nasal obstruction, some patients with moderate to severe AR do not respond to current treatments, including the combined administration of different types of anti-allergic medicine. Thus, new options for AR treatment are needed. This study aimed to evaluate the effects of combined treatment with a novel inhibitor of hematopoietic prostaglandin D synthase (HPGDS), TAS-205, and different types of anti-allergic medicine on nasal obstruction in AR. Firstly, we demonstrated that TAS-205 selectively inhibited prostaglandin D 2 (PGD 2 ) synthesis in an enzymatic assay in a cell-based assay and in vivo models of AR. Moreover, treatment with TAS-205 alone suppressed eosinophil infiltration into the nasal cavity and late phase nasal obstruction. The combined administration of TAS-205 with montelukast, a cysteinyl leukotriene receptor 1 antagonist, showed significant additive inhibitory effects on eosinophil infiltration and late phase nasal obstruction compared to treatment with each agent alone. In contrast, concomitant treatment with TAS-205 and fexofenadine, a histamine H 1 blocker, showed inhibitory effects on late phase and early phase nasal obstruction, although the magnitude of the inhibitory effects upon combined administration was comparable to that of each single treatment. These results suggest that combined treatment with an HPGDS inhibitor and different types of anti-allergic medicine may be a promising strategy to control nasal obstruction in AR patients., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We report a series of clinical cases associated with parasitism by the Ornithodoros brasiliensis tick in a group of travelers in the Caxias do Sul municipality, Southern Brazil. These cases draw attention to underdiagnosed noninfectious syndromes caused by ticks with restricted local distributions., (Copyright © 2019 Marketing EDGE.org. Published by Elsevier Inc. All rights reserved.)

Background: Solar urticaria (SU) is a rare photodermatosis causing a significant impact on patients' quality of life (QoL), and treatment is often challenging., Aim: To analyse clinical experience with a tailored stepwise therapeutic approach., Methods: A retrospective cohort design was used. Patients with suspected SU underwent laboratory investigations and photoprovocation. Those with a high minimal urticaria dose (MUD) were treated with a single antihistamine (protocol 1), and those with a lower MUD received three types of antihistamines (protocol 2); both protocols included a leucotriene receptor antagonist (LRA). In cases of failure, treatment was switched to omalizumab at doses of < 300 mg/month with incremental dosage increases as necessary (monthly dose range, 150-600 mg/month). Symptom relief and photoprovocation under treatment were evaluated., Results: In total, 30 patients (10 men, 20 women) were enrolled. Most (87%) were sensitive to visible light (1-70 J/cm 2 ) with or without extension to ultraviolet A. Of the 30 patients, 23 opted for our stepwise approach: 22 achieved complete remission on protocols 1 or 2 (n = 17) or after switching to omalizumab (n = 5), and another patient achieved partial remission under omalizumab. There were no treatment-related severe adverse effects., Conclusions: Symptoms of SU can be well controlled by treatment with antihistamines and an LRA tailored to the degree of photosensitivity, followed by omalizumab in refractory cases. This has important implications for patient QoL., (© 2019 British Association of Dermatologists.)

Introduction: The study presents the case report of a Wells Syndrome in a 18-year -ld female. Wells Syndrome is a rare inflammatory skin disorder which seems to present an abnormal eosinophilic response to a number of triggers., Objective: The aim of the study is to discuss several problems related to the diagnosis and treatment of Wells Syndrome., Material and Methods: Medical examination, blood tests, abdominal ultrasound and skin biopsy were performed., Results: Medical examination revealed plaques with tense blisters on feet and erythematous lesions on trunk. Blood tests showed raised anti-streptolysin O level. Skin biopsy revealed features of eosinophilic cellulitis. Oral administration of 0.5 mg per day prednisolone and antihistaminics with local therapy resulted in good clinical response., Conclusions: Sometimes several biopsy are required to establish diagnosis. In some cases lower doses of corticosteroids with antihistaminics and local anti-inflammatory treatment can by sufficient in treatment.

Objective: Current treatment options for Allergic Rhinitis (AR) may have their own limitations and side effects. This study aimed to investigate the effects of Ma-al-Shaeer (MS), a novel natural formulation based on Hordeum vulgare, in the treatment of AR compared with Fexofenadine (FX)., Methods: A total of 77 patients with AR were divided into two groups: MS group (n=38) and FX group (n=39). The first group received 15 g of dried MS powder, and the second group received 60 mg of FX twice daily for 14 days. At baseline (week zero) and after the 14-day treatment period (week two), both groups were evaluated for sneezing, rhinorrhea, nasal congestion, nasal itching, post nasal drip, eye, throat, or ear symptoms, headache, cough, mental function, quality of life scores, blood eosinophil count and total IgE levels. Rhinitis control assessment tests were conducted at week zero and again at one week after cessation of treatment (week three) in both groups., Results: All symptoms of AR except cough were significantly reduced in both groups; for nasal congestion, post nasal drip, and headache, the MS treatment was found to be superior. Rhinitis control was significantly increased after treatment in both groups (p value < 0.001). Both drugs significantly reduced total IgE levels. There was no significant change in eosinophil count in either group., Conclusion: MS formulation based on H. vulgare may be an effective treatment for AR. Further studies are needed to confirm the effect of MS as an alternative treatment in AR., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The acquired resistance of non-small cell lung cancer (NSCLC) to taxanes eventually leads to the recurrence and metastasis of tumours. Thus, the development of therapeutic strategies based on the mechanisms by which cells acquire resistance to prolong their survival rate in chemotherapy drug treatment failure patients are warranted. In this study, we found that the resistant cells acquired increased migratory and invasive capabilities, and this transformation was correlated with epithelial-mesenchymal transition (EMT) and Notch pathway deregulation in the resistant cells. Finally, we reported for the first time that terfenadine augmented the effect of epirubicin (EPI) better than Taxol and cisplatin (DDP) by inhibiting migration, invasion, and the EMT phenotype, and the combination therapy also reversed Notch signalling pathway and enhanced the accumulation of fluorescent P-gp substrate rhodamine 123 (Rh123). Similar activities of terfenadine on EPI were observed in xenografts. All of our results confirmed that terfenadine combined with EPI synergistically inhibits the growth and metastatic processes of resistant cells both in vitro and in vivo. Therefore, terfenadine or its derivatives are a promising approach for the clinical challenge of resistance in patients with advanced NSCLC., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Fexofenadine, a potent antagonist to human histamine 1 (H 1 ) receptor, is a non-sedative third generation antihistamine that is widely used to treat various human allergic conditions such as allergic rhinitis, conjunctivitis and atopic dermatitis. Encouragingly, it's been successfully used to treat canine atopic dermatitis, this supports the notion that it might have a great potential for treating other canine allergic conditions and other mammal pets such as dog. Regrettably, while there is a myriad of studies conducted on the interactions of antihistamines with human H 1 receptor, the similar studies on non-human pet H 1 are considerably scarce. The published studies using the first and second generation antihistamines drugs have shown that the antihistamine response is varied and unpredictable. Thus, to probe its efficacy on pet, the homology models of dog and cat H 1 receptors were built based on the crystal structure of human H 1 receptor bound to antagonist doxepin (PDB 3RZE) and fexofenadine was subsequently docked to human, dog and cat H 1 receptors. The docked complexes are then subjected to 1000ns molecular dynamics (MD) simulations with explicit membrane. Our calculated MM/GBSA binding energies indicated that fexofenadine binds comparably to the three receptors; and our MD data also showed the binding poses, structural and dynamic features among three receptors are very similar. Therefore, our data supported the application of fexofenadine to the H 1 related allergic conditions of dog and cat. Nonetheless, subtle systemic differences among human, dog and cat H 1 receptors were also identified. Clearly, there is still a space to develop a more selective, potent and safe antihistamine alternatives such as Fexofenadine for dog or cat based on these differences. Our computation approach might provide a fast and economic way to predict if human antihistamine drugs can also be safely and efficaciously administered to animals., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Solar urticaria is a rare type of inducible urticaria characterized by wheal and erythema formation shortly after exposure to sunlight or to an artificial light source; its pathophysiology is not yet entirely understood. The treatment of choice, in addition to exposure avoidance, consists in antihistamine administration., Clinical Case: This is the case of a 27-year-old woman with no personal history of allergic diseases and with a 2-year history of erythema and wheals in photo-exposed areas associated with sunlight exposure for periods longer than 10 minutes. A provocation test was carried out; she was started on fexofenadine at 4-fold the standard dose (720 mg/day). Six weeks later, a new challenge was carried out without the antihistamine being discontinued; the reaction was less severe, but she continued with erythema for the first 60 minutes post-exposure. After 3 months on high-dose antihistamines, she referred marked improvement in her quality of life and tolerance to brief sunlight exposure (for less than 15 minutes)., Conclusions: Solar urticaria is a rare process but with a high impact on the patient. The use of antihistamines partially relieves symptoms and allows better tolerance to lighting expositions.

FXF is a third-generation antihistamine drug and osthole is assumed a natural antihistamine alternative. This paper compares peripheral blood mononuclear cell (PBMC) incubation with FXF and osthole, by studying FXF, osthole and histamine cytokine secretion in PBMC in vitro cultures. Mabtech kits determined the interleukins IL-1β, IL-4, IL-10, IL-13 and TNF-α. The influence of the above active substances on cytokine secretion in PBMC's and serum was assessed: cytokines were IL-1β, IL-4, IL-10, IL-13 and TNF-α; and cytokine levels secreted by untreated PBMCs in pure culture medium formed the absolute control (ctrl). We determined that osthole affects PBMC cytokine secretion to almost precisely the same extent as FXF (IL-1β, IL-4, IL-10 and TNF). In addition osthole had greater IL-13 blocking ability than FXF. Moreover, we observed significantly decreased IL-4 level in histamine/osthole theatment compared to histamine alone. Meanwhile, FXF not significantly decrease the level of IL-4 increased by histamine. This data indicates osthole's strong role in allergic inflamation. All results confirm our hypothesis that osthole is a natural histamine antagonist and therefore can be beneficially used in antihistamine treatment of conditions such as allergies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

BackgroundCutaneous reactions to tattoos are most commonly granulomatous or lichenoid.PurposeWe describe a woman who developed a lymphocytic reaction following a cosmetic tattoo procedure with black dye. The reaction occurred not only at the site of the tattoos (eyebrows and eyelash lines), but also in non-tattooed skin (bilateral malar cheeks).Methods and MaterialsWe reviewed PubMed for the following terms: cosmetic, dye, granuloma, granulomatous, lichenoid, lymphocytic, perivascular, pigment, pseudolymphoma, reaction, and tattoo. We also reviewed papers containing these terms and their references.ResultsHistopathologic examination of the left eyebrow and left cheek punch biopsies showed predominantly a perivascular lymphocytic reaction secondary to exogenous tattoo pigment.ConclusionsPerivascular lymphocytic reaction is an uncommonly described complication of tattooing. Our patient had an atypical presentation since she had no prior tattoos, became symptomatic only a few days after the procedure, reacted to black dye, and involved skin both within and outside the confines of the tattoos. Her symptoms and lesions resolved after treatment with systemic and topical corticosteroids and oral antihistamines.

Objective: To observe the effect of combined therapy on seasonal allergic rhinitis(AR) and quality of life. Method: Ninety-six patients with severe seasonal AR unresponsive to intranasal corticosteroids alone were divided randomly into nasal budesonide group(group A),Nasal Budesonide combined with fexofenadine hydrochloride group(group B),and budesonide combined with montelukast group(group C).The symptom scores,Uni-VAS,and rhinoconjunctivitis quality of life(RQLQ) were evaluated 2 and 4 weeks after treatment initiation. Result: In the group B and C,the symptom scores,Uni-VAS,and RQLQ were significantly lower than the group A( P <0.05).As for nasal itching(after 2 weeks),rhinorrhea and sneezing,the symptom scores and Uni-VAS of group B were significantly lower than that of group C( P <0.05).However,compared to group B,the improvement of nasal obstruction in group C was much better( P <0.05).There was no significant difference in other symptoms and RQLQ. Conclusion: For patientswith severe seasonal AR unresponsive to intranasal corticosteroids alone,combined therapy can help alleviate clinical symptoms and improve quality of life.The combination of drugs should be individulized based on the severity of symptoms., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Aims: We aimed to demonstrate the feasibility and investigate the safety of a novel, self-expanding trans-catheter heart valve in a selected patient population with severe aortic stenosis., Methods and Results: Between January and September 2013, a total of 21 patients with symptomatic severe aortic stenosis were eligible for transcatheter aortic valve implantation (TAVI) with the self-expanding NVT Allegra bioprosthesis (New Valve Technology, Hechingen, Germany) at two cardiovascular centres. Patients were elderly (age 83.8±4 years), predominantly female (95.2%), and all were considered to be at prohibitive risk for surgical aortic valve replacement (logistic EuroSCORE 30.4±11%). Procedural and device success was achieved in 95.2% and 85.7%, respectively. Echocardiographic assessment at discharge showed favourable haemodynamic results with a reduction of the mean transvalvular aortic gradient from 48.0±21 mmHg to 8.9±3 mmHg. In the majority of patients (90.5%), none or trace aortic regurgitation was recorded. Permanent pacemaker implantation was required in 23.8% of patients within the first 30 days of follow-up. Apart from one procedural death, no other serious adverse events were observed during the periprocedural period. TAVI with the NVT Allegra system was highly effective in alleviating symptoms and reducing NYHA functional class at 30-day follow-up., Conclusions: The first-in-human experience with the NVT Allegra transcatheter heart valve prosthesis was associated with a high rate of procedural success. Furthermore, the NVT Allegra bioprosthesis was able to achieve favourable haemodynamic results and effectively alleviate symptoms at 30-day follow-up. The larger, multicentre NAUTILUS study will provide further information on the safety and efficacy of this novel, second-generation transcatheter aortic bioprosthesis.

Background: Solar urticarial (SU) is characterized by erythema, whealing, and/or pruritus occurring minutes after sun exposure. Treatment is difficult and often unsatisfactory., Objectives: To determine the action spectra and minimal urticaria dose (MUD) and to tailor a treatment regimen graded according to disease severity in a series of patients with SU., Patients and Methods: Eleven patients (seven females, four males, age range: 5-60 years) with a clinical history suggestive of SU, verified by photo-provocation tests to ultraviolet A (UVA), visible light, and/or UVB, were treated with various combinations of antihistamines and leukotriene receptor antagonist., Results: All patients were sensitive to visible light (median MUD 50 J/cm(2)). Three patients were sensitive to UVA (median MUD 3.75 J/cm(2)), and one patient was sensitive to UVB (MUD of 0.03 J/cm(2)). Two patients experienced a spontaneous remission without treatment. One patient declined treatment. The remaining eight patients were managed by a combination of antihistamines (desloratidine, fexofenadine, cetirizine HCl) and a leukotriene receptor antagonist (montelukast). Seven of the 8 patients experienced a sustained remission of symptoms and signs following treatment., Conclusions: Photoprovocation for SU with determination of action spectra and MUD enables specifically tailored treatment regimens consisting of combinations of antihistamines and leukotriene receptor antagonist., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Filariae are tissue-invasive nematodes that cause diseases such as elephantiasis and river blindness. The goal of this study was to characterize the role of histamine during Litomosoides sigmodontis infection of BALB/c mice, a murine model of filariasis. Time course studies demonstrated that while expression of histidine decarboxylase mRNA increases throughout 12 weeks of infection, serum levels of histamine exhibit two peaks-one 30 minutes after primary infection and one 8 weeks later. Interestingly, mice treated with fexofenadine, a histamine receptor 1 inhibitor, demonstrated significantly reduced worm burden in infected mice compared to untreated infected controls. Although fexofenadine-treated mice had decreased antigen-specific IgE levels as well as lower splenocyte IL-5 and IFNγ production, they exhibited a greater than fourfold rise in eosinophil numbers at the tissue site where adult L. sigmodontis worms reside. Fexofenadine-mediated clearance of L. sigmodontis worms was dependent on host eosinophils, as fexofenadine did not decrease worm burdens in eosinophil-deficient dblGATA mice. These findings suggest that histamine release induced by tissue invasive helminths may aid parasite survival by diminishing eosinophilic responses. Further, these results raise the possibility that combining H1 receptor inhibitors with current anthelmintics may improve treatment efficacy for filariae and other tissue-invasive helminths.

The aim of this study was to evaluate the effect of fexofenadine on intestinal inflammation. HCT116 and COLO205 cells were pretreated with fexofenadine and then stimulated with tumor necrosis factor (TNF)-α. Interleukin (IL)-8 expression was determined by real-time reverse-transcription polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. DNA-binding activity of nuclear factor-κB was assessed by electrophoretic mobility shift assay. The molecular markers of endoplasmic reticulum (ER) stress were evaluated by Western blot analysis and PCR. In the acute colitis model, mice were given 4% dextran sulfate sodium (DSS) for 5 days with or without fexofenadine. IL-10(-/-) mice were used to evaluate the effect of fexofenadine on chronic colitis. Fexofenadine significantly inhibited the upregulated expression of IL-8 in HCT116 and COLO205 cells stimulated with TNF-α. Fexofenadine suppressed nuclear factor-κB DNA-binding activity. C/EBP homologous protein mRNA expression was enhanced in the presence of TNF-α, and it was dampened by pretreatment of fexofenadine. In addition, the induction of ER stress markers caspase-12 and p-eukaryotic initiation factor 2 (eIF2)-α was significantly suppressed by the pretreatment of fexofenadine. Administration of fexofenadine significantly reduced the severity of DSS-induced murine colitis, as assessed by the disease activity index, colon length, and histology. In addition, the DSS-induced phospho-IκB kinase activation was significantly decreased in fexofenadine-pretreated mice. Finally, fexofenadine significantly reduced the severity of colitis and the immunoreactivity of caspase-12 and p-eIF2-α in IL-10(-/-) mice as compared with controls. These results suggest that fexofenadine is a potential therapeutic agent for the treatment of inflammatory bowel disease., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)

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.

Myocardial infarction occurring during the course of type I hypersensitivity constitutes Kounis syndrome. We report a case of a 38-year-old man who presented with anterior ST elevation myocardial infarction and peripheral blood eosinophilia. He had rhinitis and malaise for several days prior to presentation. There was no urticarial rash or pruritus to suggest hypersensitivity. Coronary angiogram revealed only mild plaque disease. Blood investigations revealed moderate eosinophilia and elevated IgE levels. CT of the thorax revealed fluid extravasation at multiple sites. Screening for a possible secondary cause for eosinophilia revealed hypersensitivity to multiple antigens. A diagnosis of Kounis syndrome was made. Within days of starting steroids and antihistamines, the patient's eosinophil count returned to normal with improvement of clinical picture. This case differs from classical Kounis syndrome as there was no acute allergic reaction (except atopic rhinitis). Fluid extravasation at multiple sites has not been described in previous cases., (2015 BMJ Publishing Group Ltd.)

Olopatadine is one of the second-generation H1 antihistamines that were used for treating allergic disorders initially in Asia, and now also in Western countries. Whereas several trials compared the efficacy on chronic urticaria among second-generation H1 antihistamines, no study has directly compared the clinical efficacy between olopatadine and other H1 antihistamines in patients with chronic idiopathic urticaria (CIU). In this study, we address this issue for the first time and conclude that olopatadine is a good candidate for the treatment of CIU., (© 2015 S. Karger AG, Basel.)

In this study, we report on the efficacy of combination therapy of second-generation antihistamine antagonist, fexofenadine hydrochloride, and leukotriene receptor inhibitor, montelukast sodium, for the treatment of 15 prurigo nodularis or pemphigoid nodularis patients, in whom conventional therapy was ineffective. All patients received 10 mg montelukast once a day and 240 mg fexofenadine twice a day for 4 weeks in addition to other medications they had been taking. We assessed the manifestations of the lesions and itching intensity before and after the therapy, and we evaluated each patient as (i) markedly improved, (ii) improved, (iii) slightly improved, (iv) no change, (v) worse. Two patients (13.3%) were evaluated as markedly improved, and the lesions of one patient completely disappeared. Three patients (20.0%) were evaluated as improved, and six patients (40.0%) as slightly improved. Thus, 11 of 15 cases (73.3%) improved by combination therapy of fexofenadine and montelukast, in which nine cases (75.0%) of prurigo nodularis and two cases (66.7%) of pemphigoid nodularis were involved. No patients revealed any side effects. This study revealed that combination therapy of fexofenadine and montelukast was effective for some patients with conventional therapy-resistant prurigo nodularis and pemphigoid nodularis., (© 2013 Wiley Periodicals, Inc.)

Objective: The aim of this research was to evaluate analgesic, antioxidant, metabolic, and cytotoxic effects of pregabalin (PGB), which is widely applied for the treatment of neuropathic pain syndromes in diabetic patients., Methods: We used the streptozotocin (STZ) model of painful diabetic neuropathy (PDN) in mice and we measured the effect of intraperitoneally administered PGB on tactile and thermal nociceptive thresholds in the von Frey and hot plate assays, respectively. The influence of PGB on the motor coordination of diabetic animals was investigated in the rotarod test. In vitro in HepG2 and 3T3-L1 cell lines cytotoxicity of PGB, its influence on glucose utilization, and lipid accumulation were assessed. The antioxidant capacity of PGB was evaluated spectrophotometrically using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical method., Results: Pregabalin was a very efficacious antiallodynic and analgesic drug capable of increasing the pain thresholds for tactile allodynia and thermal hyperalgesia in diabetic mice. In the von Frey test at a dose of 30 mg/kg it elevated the pain threshold for 168% versus diabetic control and in the hot plate test this dose prolonged the latency time to pain reaction for 130% versus control value of diabetic mice. No motor deficits were observed in PGB-treated diabetic animals. In vitro PGB did not influence glucose utilization or lipid accumulation. No antioxidant or cytotoxic effects of PGB were observed at concentrations 1-100 μM., Discussion and Conclusion: Our experiments demonstrated significant antiallodynic and analgesic properties of PGB in mice. In vitro studies showed that this drug is metabolically neutral. It did not cause motor coordination impairments in diabetic animals either. These effects might be of great importance for diabetic patients.

Objective: The MDR1 gene encodes for P-glycoprotein (P-gp), which is an efflux transporter at the cell membrane. The P-gp has wide substrate specificity for multiple medications, including the antiallergic drug fexofenadine. In this study, we investigated the possible association between three common MDR1 gene polymorphisms (G2677T, C3435T, and C1236T), and the anti-allergic effect of fexofenadine among Jordanians., Materials and Methods: An assessment of the severity of allergic rhinitis symptoms was performed for all patients (n = 260) pre- and 7 days into fexofenadine. MDR1 polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)., Results: Relative to baseline, fexofenadine treatment was associated with significant reduction in allergic individual and total scores (p < 0.0001). Male gender was associated with less mean reduction in total allergic rhinitis symptoms score than in female (p < 0.05). In multivariate analysis, male gender was negatively correlated with response to fexofenadine (p = 0.01). The MDR1 gene C1236T polymorphism showed significant correlation with changes in total symptoms score from baseline in males (p < 0.05) but not in females. No significant correlation between fexofenadine response parameters and G2677T or the C3435T polymorphism was observed., Conclusions: The MDR1 gene polymorphism C1236T was associated with the anti-allergic effect of fexofenadine among male Jordanians.

This randomized, double-blind, placebo-controlled crossover study compared inhibition by one 5 mg dose of levocetirizine with two 60 mg doses of fexofenadine separated by 12 h of histamine-induced wheal and flare responses in 9 Caucasian and 9 Japanese healthy male volunteers. Levocetirizine was more inhibitory than fexofenadine on wheal, flare and pruritus (p < 0.005). Variability, evaluated from the standard deviation of inhibition, ranged from 14% to 23.2% for levocetirizine and 65.4% to 112.4% for fexofenadine. Levocetirizine had a faster onset of action (30-90 min versus 2 h), shorter time to maximum effect (3-4 versus 3-6 h) and longer duration of action (at least 24 h versus ~12 h) than fexofenadine. The plasma levels of levocetirizine rose more quickly, reached higher levels, were more consistent and decreased slower than those of fexofenadine. There were no clinically significant ethnic differences in responsiveness to the drugs.

The number of diagnostic positron emission tomography/computed tomography (PET/CT) procedures performed in the USA and worldwide is rapidly increasing. Although the benefits of these procedures are obvious, the increasing use of radiopharmaceuticals requires a better understanding of potential adverse affects and their proper management. We present herein the first report of an allergic reaction to fluorodeoxyglucose in the setting of repeated PET/CT scans for restaging purposes in a patient with pyriform sinus cancer.

The year 2012 has seen relevant changes in Polish pharmaceutical legislation and drug reimbursement, among others limiting the reimbursement solely to indications stated in the Summaries of Product Characteristics (SPCs). A discrepancy with expert recommendations became apparent. The aim of this study was to analyze discordances between up-to-date expert recommendations, the SPCs in force, and the evidence for the effectiveness of recommended drugs in urticaria. Guidelines for the treatment of urticaria issued by Polish and international expert bodies were analyzed, along with the SPCs. A systematic review of clinical trials of recommended drugs was carried out. Of drugs recommended by the experts, 203 were authorized in Poland for urticaria treatment, including 167 oral preparations of second-generation antihistamines (SGAH, 8 active substances), 29 oral preparations of first-generation antihistamines (6 substances), 4 preparations of systemic glucocorticosteroids (2), 2 topical glucocorticosteroid preparations (2) and one combined preparation of human immunoglobulin with histamine. Among products both recommended by experts and licensed for the treatment of urticaria in Poland, high or moderate-level of evidence of effectiveness was available for 7 active substances (bilastine, cetirizine, desloratadine, fexofenadine, loratadine, levocetirizine, rupatadine). Nevertheless, 39% of SGAH available in Poland (66 preparations of cetirizine, emedastine, levocetirizine, loratadine or fexofenadine) were registered exclusively for "chronic idiopathic urticaria" - a diagnosis inconsistent with the current state of medical knowledge. We conclude that there exist considerable discrepancies between expert recommendations for the pharmacotherapy of urticaria, the licensed use of drugs as defined in Summaries of Product Characteristics and scientific evidence for their effectiveness.

Background: Utilities of pertinent clinical outcomes are crucial variables for assessing the benefits and risks of drugs, but numerical data on utilities may be unreliable or altogether missing. We propose a method to incorporate qualitative information into a probabilistic decision analysis framework for quantitative benefit-risk assessment., Objective: To investigate whether conclusive results can be obtained when the only source of discriminating information on utilities is widely agreed upon qualitative relations, for example, ''sepsis is worse than transient headache'' or ''alleviation of disease is better without than with complications.'', Method: We used the structure and probabilities of 3 published models that were originally evaluated based on the standard metric of quality-adjusted life years (QALYs): terfenadine versus chlorpheniramine for the treatment of allergic rhinitis, MCV4 vaccination against meningococcal disease, and alosetron for irritable bowel syndrome. For each model, we identified clinically straightforward qualitative relations among the outcomes. Using Monte Carlo simulations, the resulting utility distributions were then combined with the previously specified probabilities, and the rate of preference in terms of expected utility was determined for each alternative., Results: Our approach conclusively favored MCV4 vaccination, and it was concordant with the QALY assessments for the MCV4 and terfenadine versus chlorpheniramine case studies. For alosetron, we found a possible unfavorable benefit-risk balance for highly risk-averse patients not identified in the original analysis., Conclusion: Incorporation of widely agreed upon qualitative information into quantitative benefit-risk assessment can provide for conclusive results. The methods presented should prove useful in both population and individual-level assessments, especially when numerical utility data are missing or unreliable, and constraints on time or money preclude its collection.

Urticaria, and especially chronic spontaneous urticaria (CSU), is a difficult condition to treat. Consequently, clinicians need to use the best H(1)-antihistamines currently available and the pharmaceutical industries need to keep developing H(1)-antihistamines that are more effective than the ones we have today. To do this we need to be able to compare the clinical efficacy of both established and new drugs. Obviously, the ideal way to do this is to use head-to-head studies in CSU. However, such studies are extremely expensive and, in the case of novel molecules, have ethical and logistical problems. Consequently, we need to have predictive models. Although determination of Ki, an indicator of the in vitro potency of an H(1)-antihistamine, may help in the initial selection of candidate molecules, the large differences in volume of distribution and tissue accumulation in humans, precludes this from being a good predictor of clinical efficacy in CSU. From the data reviewed in this article, especially the direct comparative data of desloratadine and levocetirizine in weal and flare studies and CSU, weal and flare response would appear to be the best indicator we have of effectiveness of H(1)-antihistamines in clinical practice. However, it must be pointed out that the conclusion is, essentially, based on detailed comparisons of two drugs in studies sponsored by pharmaceutical companies. Consequently, to confirm the conclusions of this review, a multicentre study independent from the influence of pharmaceutical companies should be commissioned to compare the speed of onset and effectiveness of desloratadine, fexofenadine and levocetirizine in chronic spontaneous urticaria and against histamine-induced weal and flare responses in the same patients so that we have a clear understanding of the predictive value of our models., (© 2012 Blackwell Publishing Ltd.)

Environmental challenge chambers (ECC) have been used to expose people to pollen allergens within a stable atmosphere and to examine the efficacy of treatment. Although pollinosis is one of the typical IgE-mediated type I allergic diseases, allergic inflammation is thought to contribute to the fundamental pathogenesis and prophylactic treatment may reduce exacerbations of pollinosis. The purpose of this study was to compare the efficacy of prophylactic treatment with nasal steroid (mometasone furoate nasal spray) or an antihistamine (fexofenadine) in the control of cedar pollinosis using the ECC. In a randomized, double-blind two-way crossover study, 48 patients received nasal steroid or antihistamine for 7 consecutive days (days 1-7). On day 8, patients were exposed to cedar pollen (8000 grains/m(3)) in the ECC for 3 hours. Nasal symptoms induced by pollen exposure were assessed. Total nasal symptom scores (TNSSs) during the exposure in the ECC were not significantly different between the antihistamine and the nasal steroid groups. Nasal symptoms induced by pollen exposure using the ECC persisted for up to 3 days. TNSSs after pollen exposure on days 8-11 were significantly lower in the nasal steroid group compared with the antihistamine group. Prophylactic treatment with nasal steroid is more effective than antihistamine against pollinosis, particularly in the late phase. Clinical trial registration JAPIC CTI 101182 (www.clinicaltrials.jp/user/ctiMain&#95;e.jsp).

Background: Clara cell 10-kD protein (CC10) is well known to be an immuno-suppressive protein secreted from airway epithelial cells after inflammatory stimulation and is involved in the development of allergic disorders. Although histamine H1 receptor antagonists are used for the treatment of allergic disorders, the influence of the agents on CC10 production is not well understood. In the present study, we examined the influence of a histamine H1 receptor antagonist, fexofenadine hydrochloride (FEX) on CC10 production in vitro and in vivo., Methods: Nasal epithelial cells (5 x 10(6) cells/ml) were stimulated with 20 ng/ml TNF-alpha in the presence of various concentrations of FEX for 24 hours. CC10 levels in culture supernatants were examined by ELISA. Patients with Japanese cedar pollinosis were treated orally with FEX twice a day at a single dose of 60 mg for two weeks during Japanese cedar pollen season (February 2011 to April 2011). CC10 levels in nasal secretions were also examined by ELISA., Results: The addition of FEX into cell cultures caused increase in CC10 production induced by TNF-alpha stimulation, and the minimum concentration that caused significant increase was 200 ng/ml. Oral administration of FEX also increased CC10 levels in nasal secretions from pollinosis patients along with attenuation of clinical symptoms., Conclusion: The ability of FEX to enhance CC10 production may account, at least in part, for the clinical efficacy of the agent in allergic disorders, including allergic rhinitis.

Since most first-generation antihistamines have undesirable sedative effects on the central nervous systems (CNS), newer (second-generation) antihistamines have been developed to improve patients' quality of life. However, there are few reports that directly compare the antihistaminic efficacy and impairment of psychomotor functions. We designed a double-blind, placebo controlled, crossover study to concurrently compare the clinical effectiveness of promethazine, a first-generation antihistamine, and fexofenadine and olopatadine, second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare. Further, we investigated their sedative effects on the CNS using a battery of psychomotor tests. When single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a double-blind manner to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. In the comparison among antihistamines, olopatadine showed a rapid inhibitory effect compared with fexofenadine and promethazine, and had a potent effect compared with promethazine. In a battery of psychomotor assessments using critical flicker fusion, choice reaction time, compensatory tracking, rapid visual information processing and a line analogue rating scale as a subjective assessment of sedation, promethazine significantly impaired psychomotor function. Fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as measured by wrist actigraphy. These results suggest that olopatadine at a therapeutic dose has greater antihistaminergic activity than promethazine, and olopatadine and fexofenadine did not cause cognitive or psychomotor impairment.

Conclusions: These findings suggest that the down-regulation of interleukin (IL)-5 gene expression in collaboration with the suppression of histamine H(1) receptor (H1R) gene expression in the nasal mucosa provides the basis for better therapeutic effects of preseasonal prophylactic treatment with antihistamines in patients with seasonal allergic rhinitis caused by Japanese cedar pollen., Objectives: The effects of prophylactic administration of antihistamines on the expression of IL-5 and IL-33 mRNA in the nasal mucosa of the patients with pollinosis were investigated., Methods: Eight patients had already visited the hospital before the peak pollen period and started preseasonal prophylactic treatment with antihistamines. Seventeen patients who first visited the hospital during the peak pollen period were designated as the no treatment group. After local anesthesia, nasal mucosa was obtained by scraping the inferior concha with a small spatula during the peak pollen period., Results: During the peak pollen period, the expression of IL-5 mRNA, but not that of IL-33 mRNA, in the nasal mucosa of patients receiving preseasonal prophylactic treatment with antihistamines was significantly lower in comparison with that of patients without treatment. Moreover, there was a significant correlation between the expression of IL-5 mRNA and the nasal symptoms or the expression of H1R mRNA.

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.

Background: In Japan, oral antihistamines are frequently used as the initial treatment for seasonal allergic rhinitis (SAR), and intranasal steroids are added when nasal symptoms worsen. This study aimed to evaluate whether starting treatment with fluticasone propionate nasal spray (FP) from the beginning of pollinosis symptoms and adding fexofenadine hydrochloride tablet (FEX) when SAR is aggravated could achieve improved amelioration of nasal symptoms throughout the pollen season in comparison with a treatment that involves starting with FEX and later adding FP., Methods: In this pragmatic, randomized, open-label, parallel-group trial, 51 Japanese cedar pollinosis patients (age, 16-85 years) were randomly divided and administered FP 100 mcg twice daily as an initial drug with FEX 60 mg twice daily as an additional drug and the same treatment in the reverse order. Nasal symptoms were evaluated in a daily dairy using a 4-point scale. The primary outcome was area under curve of the line representing the daily total nasal symptom score in the pollen season on a graph., Results: Initial treatment with FP was significantly (P = 0.0015) more effective than initial treatment with FEX in improving the primary outcome. The average daily total nasal symptom score in the initial treatment with FP group was better than that in the initial treatment with FEX group throughout the pollen season., Conclusions: Initiating treatment with FP and adding FEX might lead to improved outcomes for nasal symptoms in comparison with the same drugs administered in the reverse order.