piperidines and Rhinitis--Allergic

Allergic diseases are immunological exaggerations with symptoms that may interfere with life quality. Bilastine, a novel oral second-generation H-1 antihistamine, is highly selective to H-1 receptors and has anti inflammatory properties. The present evidence regarding the drug efficacy is inconsistent.. We aimed to evaluate the efficacy and safety of bilastine compared with the placebo and other active antihistamines in patients who complained either from AR or chronic urticaria.. We systematically searched the Medline, Scopus, Web of Science, and Cochrane databases for randomized controlled trials (RCTs) evaluating bilastine effects on symptomatic hyper histaminic allergic conditions. We collected data on total symptoms scores (TSS), total nasal symptom scores (TNSS), discomfort associated with these allergic conditions measured by visual analog score (VAS), and quality of life (QOL) for AR and urticaria. Other outcomes such as clinical global impression and safety profiles were reported as well. We pooled the studies in a random effect model using RevMan 5.4 software.. We included 9 RCTs comprising 3801 participants. The meta-analysis revealed that bilastine was superior to placebo, improving TSS, TNSS, VAS, and QOL in AR or chronic urticaria participants. Moreover, the bilastine was comparable to active antihistamines such as cetirizine, fexofenadine, and loratadine regarding mentioned outcomes. In addition, the novel drug was safe and tolerable with no difference in the incidence of adverse events with a placebo.. Bilastine safely improved TSS in hyper histaminic allergic conditions involving nasal symptoms in AR. It decreases the discomfort associated with the disease resulting in improving the QOL of the participants.

Topics: Benzimidazoles; Chronic Urticaria; Histamine Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic; Urticaria

Bilastine (BIL) is the new generation antihistamine that is used to relieve the symptoms of hayfever, chronic urticaria and other forms of allergic rhinitis. Chemically it is known 2-[4-[2-[4-[1- (2-ethoxyethyl) benzimidazole-2-yl] piperidine-1-yl] ethyl] phenyl]-2-methylpropane acid. The chemical structure of BIL having a hydrophilic carboxylic substituent. BIL has a longer duration of action due to its potent binding affinity to the H1 receptor. This review summarizes the properties, characteristics, chemistry along with analytical and bioanalytical methods used for estimation of BIL from different scientific articles. The literature has demonstrated some methods for quantification of BIL in various sample matrix and pharmaceutical products. Frequently and extensively used antihistaminics are in the clinic practice, a novel, effective, economic and safe analytical methodology is required for routine quality control analysis, bioavailability, and bioequivalence studies. Furthermore, this narrative review summarizes available data on chemistry, pharmacology and analysis of BIL in a different matrix.

Topics: Benzimidazoles; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic

Topics: Adolescent; Adult; Benzimidazoles; Child; Drug Interactions; Histamine H1 Antagonists; Humans; Piperidines; Pruritus; Quality of Life; Rhinitis, Allergic; Urticaria; Young Adult

Histamine, acting predominantly via the H1-receptor, is an important mediator of the symptoms of allergy. H1-antihistamines, which stabilize the receptor in its inactive form, are the treatment of choice for some chronic allergic conditions. Ebastine is a well-established secondgeneration oral H1-antihistamine that is administered once daily at a dose of 10-20 mg and is available both as a standard tablet and as a fast-dissolving tablet that disintegrates in the mouth. Ebastine has been shown to relieve symptoms in patients with allergic rhinitis or urticaria in multiple clinical trials. In addition to its antihistamine effects, the drug has modulating effects on the allergic inflammatory process, thus potentially explaining its beneficial effect on nasal obstruction in some patients. Ebastine is generally well tolerated at recommended doses and is one of the lowest-risk antihistamines with respect to adverse cognitive/psychomotor effects, as confirmed by decades of pharmacovigilance. New long-term data confirm its efficacy and tolerability during up to 1 year of treatment in patients with chronic urticaria.

Topics: Administration, Oral; Butyrophenones; Histamine; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis, Allergic; Treatment Outcome; Urticaria

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

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Because of its burden on patient's lives and its impact on asthma, allergic rhinitis must be treated properly with more effective and safer treatments. According to guidelines by Allergic Rhinitis and Its Impact on Asthma (ARIA), the classification, pathogenesis, and treatment of allergic rhinitis are well defined. Currently, second-generation antihistamines and inhaled steroids are considered the cornerstone of first-line therapy. However, new formulations of available drugs (e.g., loratadine and rupatadine oral solution, ebastine fast-dissolving tablets, and the combination of intranasal fluticasone propionate and azelastine hydrochloride), recently discovered molecules (e.g., ciclesonide, bilastine, and phosphodiesterase-4 inhibitors), immunologic targets (e.g., omalizumab), and unconventional treatments (e.g., homeopathic treatments) are currently under investigation and represent a new frontier in modern medicine and in allergic rhinitis management. The aim of this review is to provide an update on allergic rhinitis treatment, paying particular attention to clinical trials published within the past 20 months that assessed the efficacy and safety of new formulations of available drugs or new molecules.

Topics: Administration, Intranasal; Androstadienes; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Benzimidazoles; Butyrophenones; Cyproheptadine; Fluticasone; Histamine H1 Antagonists; Humans; Omalizumab; Phthalazines; Piperidines; Pregnenediones; Rhinitis, Allergic; Rhinitis, Allergic, Perennial

Bepotastine besilate 1.5% is a newly approved second-generation topical antihistamine indicated for the pruritus associated with allergic conjunctivitis. In Japan, the oral formulation is approved to manage pruritus associated with allergic rhinitis and urticaria.. Bepotastine is a piperidine derivative that antagonizes H1 receptors with high selectivity. It has been labeled a dual-acting or multiple-acting antiallergic medication, because it inhibits histamine at H1 receptors and stabilizes mast cells to prevent histamine release. Bepotastine may also have other immunoactive properties, such as inhibition of eosinophil migration, interleukin-5 (IL-5), leukotrienes (e.g., LTB4) and platelet-activating factor (PAF). Human clinical trials demonstrate the efficacy and safety of systemic and ophthalmic bepotastine for pruritus relief, limited penetration across the blood-brain-barrier and kinetics suitable for twice-daily administration.. Bepotastine besilate 1.5% ophthalmic solution is a safe and effective treatment option for allergic conjunctivitis associated pruritus. Side-effect profile is similar to other ocular antihistamine agents. Additional comparative-effectiveness studies would further advance its clinical use. Oral bepotastine is a safe and effective treatment option approved in Japan for allergic rhinitis, urticaria and pruritus associated with skin diseases.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Clinical Trials as Topic; Conjunctivitis, Allergic; Histamine H1 Antagonists; Humans; Piperidines; Pruritus; Pyridines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Urticaria

Bilastine is a new H1 antagonist with no sedative side effects, no cardiotoxic effects, and no hepatic metabolism. In addition, bilastine has proved to be effective for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Pharmacological studies have shown that bilastine is highly selective for the H1 receptor in both in vivo and in vitro studies, and with no apparent affinity for other receptors. The absorption of bilastine is fast, linear and dose-proportional; it appears to be safe and well tolerated at all doses levels in healthy population. Multiple administration of bilastine has confirmed the linearity of the kinetic parameters. The distribution in the brain is undetectable. The safety profile in terms of adverse effects is very similar to placebo in all Phase I, II and III clinical trials. Bilastine (20 mg), unlike cetirizine, does not increase alcohol effects on the CNS. Bilastine 20 mg does not increase the CNS depressant effect of lorazepam. Bilastine 20 mg is similar to placebo in the driving test. Therefore, it meets the current criteria for medication used in the treatment of allergic rhinitis and urticaria.

Topics: Animals; Automobile Driving; Benzimidazoles; Conjunctivitis, Allergic; Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome; Urticaria; Wakefulness

Management guidelines for allergic rhinitis and urticaria recommend oral second-generation antihistamines as first-line treatment. The efficacy and safety of bilastine, the newest nonsedating second-generation antihistamine, are well established in adolescents/adults with these allergic conditions. The bilastine development program for pediatric use (2-<12 years) followed EMA-authorized processes. Pharmacokinetic/pharmacodynamic simulation and modeling and a pharmacokinetic study were conducted to identify and confirm the pediatric dose (10 mg/day). A Phase III, multicenter, double-blind, randomized, placebo-controlled, parallel-group study was performed to confirm the safety of bilastine 10 mg/day in children. In this article, evidence is reviewed for use of bilastine in children with allergic rhinoconjunctivitis or urticaria. Several cases are presented which demonstrate its role in routine clinical practice.

Topics: Adolescent; Benzimidazoles; Child; Double-Blind Method; Histamine H1 Antagonists, Non-Sedating; Humans; Piperidines; Rhinitis, Allergic; Treatment Outcome; Urticaria

To evaluate the efficacy and safety of a slow-release form of bepotastine salicylate (HL151, Belion CR) in patients with perennial allergic rhinitis (PAR).. Double-blind, placebo-controlled multicenter comparative study.. Two hundred seventy-two PAR patients (aged 19-65 years) were studied to determine the efficacy and safety of HL151 (20 mg once daily administration) relative to those of a placebo in terms of improvements in total and nasal symptom scores. The subjects were randomized to the placebo (n = 138) or HL151 group (n = 134, 20 mg orally once daily for 4 weeks), and reflective and instantaneous total nasal symptom scores (TNSS) were measured daily in comparison with baseline. Among 272 subjects, 229 subjects (119 in the placebo group, 110 in the HL151 group) who completed the study were included for efficacy analysis.. Instantaneous and reflective TNSS and nasal symptoms such as rhinorrhea, nasal itching, and sneezing at 2 and 4 weeks showed that HL151 was superior to the placebo (all P < .05). There were no significant differences in terms of adverse events and adverse drug reactions between the two groups. Regarding serious adverse events, there was only one case of acute hepatitis B, which was reported not to be associated with HL151.. This multicenter trial showed that once-daily use of HL151 is efficacious and safe in adult patients with PAR and could improve compliance due to its convenience.. 1b Laryngoscope, 131:E702-E709, 2021.

Topics: Administration, Oral; Adult; Aged; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Piperidines; Pyridines; Rhinitis, Allergic; Salicylates; Sino-Nasal Outcome Test; Treatment Outcome; Young Adult

Allergic asthma is a heterogenous disorder predominantly driven by a type 2 inflammatory response to aeroallergens. Therapeutic modulation to rebalance these type 2 responses may offer clinical benefit for allergic respiratory inflammatory diseases, with the potential for disease modification. GSK2245035, a selective toll-like receptor-7 agonist, preferentially stimulates the induction of type 1 interferon alpha, reducing type 2 responses.. This study investigated whether intranasal GSK2245035 reduced allergen-induced bronchial reactivity in mild allergic asthma.. This double-blind, placebo-controlled, parallel-group Phase IIa trial randomized (1:1) participants with mild allergic asthma to intranasal GSK2245035 20 ng or placebo once weekly for 8 weeks; follow-up was conducted 1, 4, and 12 weeks after treatment. Allergen-induced late asthmatic response 1 week after treatment was measured as minimum and weighted mean forced expiratory volume in 1 second (FEV1) 4-10 hours following bronchial allergen challenge (primary endpoint). Pharmacodynamic and allergic biomarkers, and adverse events, were assessed. A Bayesian analysis framework was used; a posterior probability >0.7 denoted primary endpoint success.. Thirty-six participants were randomized (GSK2245035, n = 22; placebo, n = 14). The percentage attenuation in late asthmatic response was -4.6% (posterior probability: 0.385) and -10.5% (posterior probability: 0.303) for minimum and weighted mean FEV1, respectively. Type 2 responses were confirmed by changes in lung function, eosinophils (blood and sputum), interleukin-5 (sputum) and fractional exhaled nitric oxide biomarkers pre- and post-bronchial allergen challenge. However, no treatment effect was observed. Adverse events were reported by 10/14 (71%) and 21/22 (95%) participants in the placebo and GSK2245035 groups, respectively; headache was the most common.. Although target engagement was observed, weekly intranasal GSK2245035 20 ng for 8 weeks did not substantially attenuate the late asthmatic response in participants with mild allergic asthma. Overall, treatment was well tolerated.

Topics: Adenine; Administration, Intranasal; Adult; Allergens; Anti-Asthmatic Agents; Asthma; Bronchial Provocation Tests; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Interferon-alpha; Male; Middle Aged; Piperidines; Proof of Concept Study; Rhinitis, Allergic; Toll-Like Receptor 7; Young Adult

Bilastine is a highly selective, non-sedating antihistamine, indicated for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Available data suggest that bilastine interferes neither with driving ability nor with flying-related performance. However, no data are available on the effect of bilastine on the driving ability in extreme conditions. Here we analyzed the effect of 7 days treatment with 20 mg bilastine in patients with allergic rhinitis and/or chronic urticaria, on psychophysical performance assessed by the Formula One (F1) high-speed simulator-driving test.. This study is a phase IV, interventional, prospective, mono-centric, single arm, open-label trial. Eighteen outpatients affected by allergic rhinitis and/or chronic urticaria, able to perform a preliminary driving test on F1 simulator were considered (V-1). First, the patients had a screening visit to assess their eligibility (V0). Visit 1 (V1), at the end of placebo before bilastine treatment and Visit 2 (V2), at the end of bilastine treatment. The primary variable parameter was the ability to maintain the vehicle in a central position at different speeds (50, 150, and 250 km/h).. Bilastine had a good safety profile and was well tolerated in terms of adverse events, laboratory parameters and vital signs. Bilastine did not have any negative effect on the ability to maintain the requested path, a constant speed as well as on attention and reactivity levels, even in extreme driving conditions.. This study is the first done in patients with allergic rhinitis and/or chronic urticaria using a F1-high speed simulator-driving test evaluating subjects' performance under bilastine treatment.

Topics: Adult; Attention; Automobile Driving; Benzimidazoles; Chronic Disease; Computer Simulation; Dizziness; Female; Histamine Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines; Prospective Studies; Rhinitis, Allergic; Urticaria; Young Adult

Topics: Administration, Intranasal; Anti-Allergic Agents; Butyrophenones; Double-Blind Method; Drug Therapy, Combination; Histamine H1 Antagonists; Humans; Mometasone Furoate; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal

Toll-like receptor 7 (TLR7) stimulation in the airways may reduce responses to aeroallergens by induction of type 1 interferons (IFNs). GSK2245035 is a novel selective TLR7 agonist in pharmaceutical development.. Assessment of safety, pharmacodynamics and nasal allergic reactivity following repeated weekly intranasal (i.n.) GSK2245035.. This randomized, double-blind, placebo-controlled study (TL7116958) was conducted over two pollen seasons (2013-2014) and follow-up study (204509) conducted 1 year later. Participants with allergic rhinitis (n=42) were randomized to receive eight weekly doses of i.n. GSK2245035 (20 ng [2014 Cohort; n=14] or 80 ng [2013 Cohort; n=14]) or placebo (n=14). Adverse events (AEs) including cytokine release syndrome AEs (CytoRS-AEs) and nasal symptoms were assessed. Nasal and serum IFN-inducible protein 10 (IP-10) were measured after doses 1 and 8, then 1 (follow-up visit [FUV] 1) and 3 (FUV2) weeks after final dose. Nasal allergen challenges (NACs) and allergic biomarker assessment (nasal, serum) were conducted at baseline, FUV1, FUV2 and at a FUV 1 year after final dose (FUV3; 2014 Cohort only). A Bayesian framework enabled probability statements for mean effect sizes.. GSK2245035 induced CytoRS-AEs (most commonly headache, median duration <1 day) in 93% of participants at 80 ng, while AE incidence at 20 ng was similar to placebo. There was no evidence of nasal inflammation. Dose-related increases in nasal and serum IP-10 were observed 24 hours after doses 1 and 8 (>95% certainty). Both doses showed a trend in reducing total nasal symptom score 15 minutes post-NAC at FUV1 and FUV2, but there was no reduction evident at FUV3. Nasal levels of selected allergic biomarkers demonstrated trends for reductions at FUV1, FUV2 and FUV3.. Weekly i.n. GSK2245035 20 ng was well tolerated and reduced allergic reactivity to nasal challenge for 3 weeks post-treatment.

Topics: Adenine; Administration, Intranasal; Adult; Aged; Allergens; Biomarkers; Drug Monitoring; Female; Follow-Up Studies; Humans; Immunization; Male; Middle Aged; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Seasons; Toll-Like Receptor 7; Treatment Outcome; Young Adult

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; Emergency Service, Hospital; Empathy; Emulsions; Endothelial Cells; Endurance Training; Energy Intake; Enterovirus A, Human; Environment; Environmental Monitoring; Enzyme Assays; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Epoxide Hydrolases; Epoxy Compounds; Erythrocyte Count; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Estrogens; Etanercept; Ethiopia; Ethnicity; Ethylenes; Exanthema; Exercise; Exercise Test; Exercise Tolerance; Extracellular Matrix; Extracorporeal Membrane Oxygenation; Eye Infections, Fungal; False Negative Reactions; Fatty Acids; Fecal Microbiota Transplantation; Feces; Female; Femur Neck; Fermentation; Ferritins; Fetal Development; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fibroblasts; Fibroins; Fish Proteins; Flavanones; Flavonoids; Focus Groups; Follow-Up Studies; Food Handling; Food Supply; Food, Formulated; Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; Heart Failure; Heart Rate; Heart Transplantation; Heart-Assist Devices; HEK293 Cells; Heme; Heme Oxygenase-1; Hemolysis; Hemorrhage; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Hexoses; High-Throughput Nucleotide Sequencing; Hippo Signaling Pathway; Histamine; Histamine Agonists; Histidine; Histone Deacetylase 2; HIV Infections; HIV Reverse Transcriptase; HIV-1; Homebound Persons; Homeodomain Proteins; Homosexuality, Male; Hospice and Palliative Care Nursing; HSP70 Heat-Shock Proteins; Humans; Hyaluronan Receptors; Hydrogen; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemia; Hypoglycemic Agents; Hypoxia; Idiopathic Interstitial Pneumonias; Imaging, Three-Dimensional; Imatinib Mesylate; Immunotherapy; Implementation Science; Incidence; INDEL Mutation; Induced Pluripotent Stem Cells; Industrial Waste; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; Molecular Structure; Molecular Weight; Multilocus Sequence Typing; Multimodal Imaging; Muscle Strength; Muscle, Skeletal; Muscular Diseases; Mutation; Mycobacterium tuberculosis; Myocardial Stunning; Myristates; NAD(P)H Dehydrogenase (Quinone); Nanocomposites; Nanogels; Nanoparticles; Nanotechnology; Naphthalenes; Nasal Cavity; National Health Programs; Necrosis; Needs Assessment; Neoadjuvant Therapy; Neonicotinoids; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm Transplantation; Neoplasms; Neoplastic Stem Cells; Netherlands; Neuroblastoma; Neuroprotective Agents; Neutrophils; NF-kappa B; NFATC Transcription Factors; Nicotiana; Nicotine; Nitrates; Nitrification; Nitrites; Nitro Compounds; Nitrogen; Nitrogen Dioxide; North Carolina; Nuclear Magnetic Resonance, Biomolecular; Nuclear Proteins; Nucleic Acid Hybridization; Nucleosomes; Nutrients; Obesity; Obesity, Morbid; Oceans and Seas; Oncogene Protein v-akt; Oncogenes; Oocytes; Open Reading Frames; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Outpatients; Ovarian Neoplasms; Ovariectomy; Overweight; Oxazines; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxides; Oxidoreductases; Oxygen; Oxygen Inhalation Therapy; Oxygenators, Membrane; Ozone; Paclitaxel; Paenibacillus; Pain Measurement; Palliative Care; Pancreatic Neoplasms; Pandemics; Parasympathetic Nervous System; Particulate Matter; Pasteurization; Patient Preference; Patient Satisfaction; Pediatric Obesity; Permeability; Peroxiredoxins; Peroxynitrous Acid; Pharmaceutical Services; Pharmacists; Pharmacy; Phaseolus; Phenotype; Phoeniceae; Phosphates; Phosphatidylinositol 3-Kinases; Phospholipid Transfer Proteins; Phospholipids; Phosphorus; Phosphorylation; Photoperiod; Photosynthesis; Phylogeny; Physical Endurance; Physicians; Pilot Projects; Piperidines; Pituitary Adenylate Cyclase-Activating Polypeptide; Plant Extracts; Plant Leaves; Plant Proteins; Plant Roots; Plaque, Atherosclerotic; Pneumonia; Pneumonia, Viral; Point-of-Care Testing; Polyethylene Glycols; Polymers; Polysorbates; Pore Forming Cytotoxic Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postprandial Period; Poverty; Pre-Exposure Prophylaxis; Prediabetic State; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Prenatal Exposure Delayed Effects; Pressure; Prevalence; Primary Graft Dysfunction; Primary Health Care; Professional Role; Professionalism; Prognosis; Progression-Free Survival; Prolactin; Promoter Regions, Genetic; Proof of Concept Study; Proportional Hazards Models; Propylene Glycol; Prospective Studies; Prostate; Protein Binding; Protein Biosynthesis; Protein Isoforms; Protein Kinase Inhibitors; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Transport; Proteoglycans; Proteome; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; 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Allergic rhinitis (AR) is a common chronic disease, which has significant detrimental effect on well-being and quality of life as well as substantial socio-economic impact. Combination pharmacotherapy is utilized by 40-50% of patients to treat their symptoms.. To compare the effects of intranasal fluticasone furoate (FF)/levocabastine (LEVO) fixed-dose combination (FDC) with each component alone on allergen-induced nasal and ocular symptoms.. A randomized, double-blind, placebo-controlled, three-way, incomplete block, cross-over, proof-of-concept study in 71 patients with AR, evaluated FF 100 μg, LEVO 200 μg and FDC (FF 100/LEVO 200 μg), once daily via intranasal spray for 8 days. On days 1 and 8, total nasal symptom score (TNSS) and total ocular symptom score (TOSS) were assessed every 15 min during a 4-h allergen exposure in the Vienna Challenge Chamber. The primary endpoint was Day 8 weighted mean TNSS.. After 8 days, FDC resulted in both statistically and clinically significant reductions in mean TNSS compared with FF and LEVO alone [adjusted mean differences (95% CI): FDC vs. FF: -2.26 (-2.90, -1.62); FDC vs. LEVO: -2.57 (-3.21, -1.93)]. All active treatments were significantly superior to placebo [adjusted mean difference (95% CI) from placebo: FDC: -4.1 (-4.86, -3.34); FF: -1.84 (-2.66, -1.03); LEVO: -1.53 (-2.34, -0.72)]. Onset of action was rapid following FDC and LEVO treatment with an approximate two unit reduction in mean TNSS from pre-dose levels by 30 min and 1 h. Mean TOSS was also reduced following all active treatments relative to placebo (range 0.6-0.8 unit reduction). All treatments were equally well tolerated.. These results suggest that once daily FF/LEVO FDC could provide a clinical therapeutic advantage to existing standard monotherapies in the treatment of moderate-to-severe AR, and support progression to evaluation in larger phase III clinical studies.

Topics: Adolescent; Adult; Aged; Androstadienes; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic

Modulation of the airways' immune milieu is a key therapeutic goal for remission from respiratory allergies. To explore this hypothesis, GSK2245035, a selective Toll-like receptor 7 (TLR7) agonist with preferential Type-1 interferon (IFN)-stimulating properties, was developed for intranasal application. Doses for clinical assessment were extrapolated from translational biomarker studies in primates. Randomized, double-blind, placebo-controlled trials in healthy volunteers and patients with allergic rhinitis demonstrated that intranasal GSK2245035 doses <100 ng were tolerated and did not cause nasal inflammation. Higher doses were not tested due to considerable cytokine release syndrome-related symptoms observed at 100 ng. Clear target engagement, reflected by local and peripheral increase of IFN-gamma-inducible protein-10, was observed at 20 ng, indicating IFN-stimulated immune changes at tolerated doses. Repeat intranasal administration at weekly intervals did not tolerize or amplify the pharmacological response. Intranasal GSK2245035 has an acceptable safety profile at doses that induce local TLR7-mediated immune responses.

Topics: Adenine; Administration, Intranasal; Adolescent; Adult; Animals; Anti-Allergic Agents; Biomarkers; Chemokine CXCL10; Double-Blind Method; Drug Administration Schedule; Female; Humans; Macaca fascicularis; Male; Middle Aged; No-Observed-Adverse-Effect Level; Piperidines; Rhinitis, Allergic; Risk Assessment; Toll-Like Receptor 7; Treatment Outcome; Young Adult

To test the hypothesis that intranasal levocabastine (LEVO) may provide benefits as a oncedaily treatment in allergic rhinitis (AR), this non-inferiority study compared the effect at steady state of once- and twice-daily dosing with LEVO on allergen-induced nasal symptoms in AR patients.. This was a randomized, double-blind, three-way cross over study evaluating the effects of repeat doses of LEVO 200 µg once-daily, LEVO 200 µg twice-daily (total dose 400 µg) and placebo, all via intranasal spray, in 78 AR patients. The primary endpoint was weighted mean total nasal symptom score (TNSS) during a 4-hour allergen exposure in the Environmental Exposure Chamber measured at trough pharmacokinetic levels either 12 (LEVO twice-daily) or 24 (LEVO once-daily) hours post-dose.. After 7 days dosing, the difference in weighted mean TNSS (0-4 hours) following LEVO once-daily versus twice-daily was 0.23 units (95% CI -0.36, 0.82), demonstrating noninferiority between the two LEVO dosing regimens by meeting the pre-specified criterion of an upper limit of 95% CI<1.0. Both dosing regimens of LEVO resulted in a statistically significant reduction in mean TNSS compared with placebo (adjusted mean difference from placebo: LEVO once-daily: -1.12 (95% CI -1.71, -0.53); LEVO twice-daily: -1.35 (-1.94, -0.76)), meeting the pre-specified criterion for superiority (upper limit of 95% CI<0). All treatments were well-tolerated.. The results of this study support the hypothesis that at steady state LEVO 200 µg taken once-daily provides similar benefit to LEVO 200 µg dosed twice-daily.

Topics: Adult; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines; Rhinitis, Allergic; Young Adult

Th2 and Th17 immune response contribute to allergic rhinitis (AR) development. Targeting Th2 and Th17 response has been shown to ameliorate AR. Ibrutinib is an inhibitor for IL2-inducible T-cell kinase, which can promote Th2 and Th17 immune response. We sought to investigate the effect of ibrutinib on AR and the underlying mechanisms. We established house dust mite-induced AR mouse model and treated AR mice with ibrutinib. The symptoms of AR, serum level of immunoglobulin E, percentage of Th1, Th2, Th17, and Treg in nasal lymphoid tissues were monitored. We also established in vitro T cell differentiation cell culture model. The T cells were treated with ibrutinib and the expression of specific transcriptional factors and cytokines was measured. The activation of PLC-γ1/calcium/NFAT2 signaling pathway was detected. Ibrutinib treatment had no effects on the development of lymphocytes and myeloid cells, but alleviated AR symptoms and decreased Th2 cell population in nasal lymphoid tissue. Meanwhile, iburitnib suppressed Th2 and Th17 differentiation in vitro. Moreover, iburitnib prevented phosphorylation of PLC-γ1and nuclear translocation of NFAT2 in Th2 cells. Our results suggested that ibrutinib could ameliorate AR symptoms through suppression of Th2 differentiation in AR mouse model.

Topics: Adenine; Animals; Cell Differentiation; Cytokines; Disease Models, Animal; Mice; Mice, Inbred BALB C; Nasal Mucosa; Piperidines; Protein-Tyrosine Kinases; Rhinitis; Rhinitis, Allergic; Th2 Cells

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

Topics: Acetates; Animals; Anti-Allergic Agents; Cell Line; Cyclopropanes; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Enzyme Inhibitors; Guinea Pigs; Humans; Intramolecular Oxidoreductases; Lipocalins; Male; Morpholines; Nasal Mucosa; Nasal Obstruction; Ovalbumin; Piperidines; Prostaglandin D2; Pyrroles; Quality of Life; Quinolines; Rats; Rhinitis, Allergic; Sulfides; Terfenadine

Bilastine is an H1-antihistamine approved for symptomatic treatment of patients with allergic rhinoconjunctivitis or urticaria. The safety profile of bilastine in clinical trials of allergic rhinoconjunctivitis or urticaria, assessed by type and frequency of adverse events (AE), was similar to that of placebo.. As part of the risk management plan for bilastine, the safety profile of bilastine in the elderly was assessed.. A prospective, multicenter, observational, open-label, 3-month follow-up study was performed to assess the safety profile of bilastine 20 mg in patients aged ≥65 years with allergic rhinoconjunctivitis and/or urticaria.. A total of 74 of 146 patients (50.7%) reported 129 treatment-emergent AEs (TEAE) during the study period. The incidence of TEAEs was low, with monthly and quarterly rates of 0.29 (95% confidence intervals [CI], 0.229-0.367) and 0.88 (95% CI, 0.688-1.100), respectively. Monthly and quarterly incidence rates were 0.04 (95% CI, 0.016-0.082) and 0.12 (95% CI, 0.048-0.246), respectively, for related TEAEs (eight TEAEs in seven patients) and were 0.02 (95% CI, 0.003-0.048) and 0.05 (95% CI, 0.010-0.143), respectively, for serious TEAEs (five TEAES in three patients). All serious TEAEs were considered to be unrelated to bilastine.. Bilastine 20 mg showed a favorable safety profile with a low incidence of TEAEs in patients aged ≥65 years. The results were in accordance with the known safety profile of bilastine 20 mg and incidence of AEs reported in previous studies and described in the approved summary of product characteristics.

Topics: Aged; Aged, 80 and over; Benzimidazoles; Conjunctivitis, Allergic; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Incidence; Male; Piperidines; Prospective Studies; Rhinitis, Allergic; Spain; Urticaria

The aim of this study was to determine whether there were differences in health-related quality of life of patients with allergic rhinitis treated with bilastine 20 mg compared to those treated with loratadine 10 mg.. This was a prospective randomised double-blinded study.. Otolaryngology outpatient clinics in Criciúma, state of Santa Catarina, Brazil.. Seventy-three patients, aged between 18 and 63 years, of whom 36 were treated with loratadine 10 mg and 37 with bilastine 20 mg with medication administered once a day for 10 days.. The outcome was quality of life as assessed by the modified Rhinoconjunctivitis Quality of Life Questionnaire (RQLQm), which was applied at baseline and after 10 days of treatment.. The use of bilastine 20 mg or loratadine 10 mg significantly reduced RQLQm scores after 10 days of treatment (P < 0.001); however, there was no statistically significant difference between the two treatment groups (P > 0.05).. Health-related quality of life in patients with allergic rhinitis improved significantly after 10 days of treatment with loratadine and bilastine, and the effectiveness of both was equivalent.

Topics: Adolescent; Adult; Anti-Allergic Agents; Benzimidazoles; Brazil; Double-Blind Method; Female; Humans; Loratadine; Male; Middle Aged; Piperidines; Prospective Studies; Quality of Life; Rhinitis, Allergic; Treatment Outcome

Allergic rhinitis (AR) is a global health problem that affects a large number of population. Piperine (PIP) has been reported to exhibit anti-inflammatory, anti-histaminic, and immunomodulatory activities; however, its antiallergic profile has not been studied.. The objective of the study was to investigate the antiallergic potential of PIP in ova-albumin (OVA)-induced AR, mast cell degranulation (MSD), and OVA-induced paw edema.. Mice were sensitized with OVA alternately on 1, 3, 5, 7, 9, 11, and 13th day. They were treated with either vehicle, PIP (10, 20, and 40 mg/kg, p.o.), or montelukast (10 mg/kg, p.o.) from the 14th to 20th day. On the 21st day, intranasal (OVA: 5% µl) challenge was done. Animals were evaluated for physiological parameters, biochemical parameters, spleen weight, expression of interleukins (IL-6 and IL-1β), and immunoglobin-E (IgE). Histopathology of nasal mucosa, lungs, and spleen was carried out. MSD and paw edema studies were made to understand the mechanism of action.. PIP (10, 20, and 40 mg/kg, p.o.) showed a significant dose-dependent protection with respect to nasal rubbing, redness of nose, and sneezing (p < 0.001) following nasal challenge. PIP dose dependently reduced histamine, NO concentration (p < 0.001), as well as reduced expression of IL-6, IL-1β, and IgE (p < 0.001) as compared with the control group. Histopathology showed inhibition of infiltration of eosinophils and hyperplasia. It dose dependently reduced MSD and paw edema (p < 0.001).. PIP acts by mast cell-stabilizing activity, exhibits immunomodulatory and anti-inflammatory activity, thereby providing an effective treatment for AR.

Topics: Acetates; Alkaloids; Animals; Anti-Allergic Agents; Benzodioxoles; Biomarkers; Cell Degranulation; Cyclopropanes; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Eosinophils; Histamine; Immunoglobulin E; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Mast Cells; Nitric Oxide; Ovalbumin; Piperidines; Polyunsaturated Alkamides; Quinolines; Rhinitis, Allergic; Spleen; Sulfides; Time Factors

Topics: Adolescent; Adult; Antioxidants; Butyrophenones; Cysts; Drug Therapy, Combination; Female; Histamine H1 Antagonists; Humans; Male; Maxillary Sinus; Maxillary Sinusitis; Middle Aged; Picolines; Piperidines; Rhinitis, Allergic; Treatment Outcome; Young Adult

Bilastine is a new, well-tolerated, nonsedating H1 receptor antihistamine. In the fasting state bilastine is quickly absorbed, but the absorption is slowed when it is taken with food or fruit juice. Therefore, it is recommended that bilastine is taken at least one hour before and no sooner than two hours after a meal. Clinical studies sponsored by the manufacturer have shown that bilastine 20 mg once daily is as efficacious as other nonsedating antihistamines in allergic rhinoconjunctivitis and chronic urticaria in individuals from 12 and 18 years of age, respectively. Bilastine is efficacious in all nasal symptoms including obstruction and in eye symptoms. The observations indicate that non-sedating antihistamines, as opposed to what has been thought previously, may be helpful in patients with allergic rhinitis in whom nasal obstruction is a major concern. Current international guidelines need to be revised in the light of the recent evidence. Research into aspects of pharmacokinetics and efficacy and adverse effect profiles of bilastine in children under 12 years of age is needed as are dose-response assessments and studies planned rigorously with the aim of assessing quality of life effects.

Topics: Administration, Oral; Benzimidazoles; Child; Conjunctivitis, Allergic; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Piperidines; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Urticaria