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1.
Recenti Prog Med ; 115(4): 1-10, 2024 Apr.
Article in Italian | MEDLINE | ID: mdl-38742412

ABSTRACT

Allergic rhinitis (AR) is a widespread disease, and its prevalence is still growing. AR may be associated with other diseases, including conjunctivitis, rhinosinusitis, asthma, food allergy, and atopic dermatitis. Diagnosis is based on history, physical examination, documentation of sensitization, such as the production of allergen-specific IgE, also using molecular diagnostics in selected patients. Treatments is based on education, engagement, allergen avoidance, non-pharmacological and pharmacological remedies, and allergen-specific immunotherapy (Ait). Symptomatic treatments mainly concern intranasal/oral antihistamines and/or nasal corticosteroids. This article also aims to discuss new management strategies for AR patients. The self-management of allergic rhinitis could include new strategies. In this regard, particular interest should be considered to intranasal corticosteroids and antihistamines without medical prescription, probiotics and other natural substances, and new formulations (tablets) of Ait.


Subject(s)
Adrenal Cortex Hormones , Desensitization, Immunologic , Histamine Antagonists , Rhinitis, Allergic , Humans , Rhinitis, Allergic/therapy , Rhinitis, Allergic/diagnosis , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Desensitization, Immunologic/methods , Histamine Antagonists/therapeutic use , Histamine Antagonists/administration & dosage , Administration, Intranasal , Allergens/immunology , Immunoglobulin E/immunology , Prevalence
2.
Luminescence ; 39(5): e4766, 2024 May.
Article in English | MEDLINE | ID: mdl-38785095

ABSTRACT

In this work, two validated approaches were used for estimating hydroxyzine HCl for the first time using resonance Rayleigh scattering (RRS) and spectrofluorimetric techniques. The suggested approaches relied on forming an association complex between hydroxyzine HCl and 2,4,5,7-tetraiodofluorescein (erythrosin B) reagent in an acidic media. The quenching in the fluorescence intensity of 2,4,5,7-tetraiodofluorescein by hydroxyzine at 551.5 nm (excitation = 527.5 nm) was used for determining the studied drug by the spectrofluorimetric technique. The RRS approach is based on amplifying the RRS spectrum at 348 nm upon the interaction of hydroxyzine HCl with 2,4,5,7-tetraiodofluorescein. The spectrofluorimetric methodology and the RRS methodology produced linear results within ranges of 0.15-1.5 µg ml-1 and 0.1-1.2 µg ml-1, respectively. LOD values for these methods were determined to be 0.047 µg ml-1 and 0.033 µg ml-1, respectively. The content of hydroxyzine HCl in its pharmaceutical tablet was estimated using the developed procedures with acceptable recoveries. Additionally, the application of four greenness and whiteness algorithms shows that they are superior to the previously reported method in terms of sustainability, economics, analytical performance, and practicality.


Subject(s)
Algorithms , Hydroxyzine , Spectrometry, Fluorescence , Hydroxyzine/analysis , Hydroxyzine/chemistry , Histamine Antagonists/analysis , Histamine Antagonists/chemistry , Scattering, Radiation , Erythrosine/chemistry , Erythrosine/analysis
3.
Allergol Immunopathol (Madr) ; 52(3): 8-16, 2024.
Article in English | MEDLINE | ID: mdl-38721950

ABSTRACT

BACKGROUND: Anaphylaxis proportions of incidence are increasing globally. However, limited data are available regarding anaphylaxis in the pediatric population of Greece. PURPOSE: The aim of the study was to evaluate management of anaphylaxis in Greek pediatric departments. METHODS: We performed a questionnaire-based study of children aged less than 16 years presenting with anaphylaxis in 10 national pediatric hospitals over a period of 2 years. Management of anaphylaxis was assessed prior to and after an informative intervention. RESULTS: In all, 127 cases of anaphylaxis were identified. Epinephrine was administered in almost half of all cases (51.2%), predominantly through intramuscular route (88.5%), while the majority of anaphylaxis patients were treated with antihistamines (92.9%) and corticosteroids (70.1%). Epinephrine was more likely administered by physicians if the elicitor was a drug (P < 0.003). Regarding long-term management, an epinephrine auto-injector was prescribed in 66.9% of patients. Follow-up information was available for most of the patients (92.9%), the majority of whom (76.3%) were referred to an allergist. More than half of these patients (63.6%) had a documented allergy follow-up, which identified a causative allergen in 53.3% of cases. No statistically significant differences were recorded prior to and after the intervention regarding management of anaphylaxis. CONCLUSIONS: This nationwide study highlighted the necessity of further improvement in terms of anaphylaxis treatment and secondary prevention measures. This presupposes appropriate education and training of healthcare professionals, thus contributing to proper and comprehensive care of the pediatric population.


Subject(s)
Anaphylaxis , Epinephrine , Humans , Anaphylaxis/epidemiology , Anaphylaxis/drug therapy , Anaphylaxis/therapy , Anaphylaxis/diagnosis , Greece/epidemiology , Child , Male , Female , Epinephrine/administration & dosage , Epinephrine/therapeutic use , Child, Preschool , Adolescent , Infant , Surveys and Questionnaires , Histamine Antagonists/therapeutic use , Histamine Antagonists/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Injections, Intramuscular
4.
Adv Exp Med Biol ; 1447: 151-167, 2024.
Article in English | MEDLINE | ID: mdl-38724792

ABSTRACT

The pathogenesis of atopic dermatitis (AD) is complex and multifactorial. However, recent advancements in the genetics and pathophysiology of AD suggest that epidermal barrier dysfunction is paramount in the development and progression of the condition (Boguniewicz M, Leung DYM, Immunol Rev 242(1):233-246, 2011). In addition to standard therapy for AD, there are a plethora of nonprescription treatment modalities which may be employed. Over-the-counter treatments for atopic dermatitis can come in the form of topical corticosteroids, moisturizers/emollients, and oral antihistamines. Though these treatments are beneficial, prescription treatments may be quicker acting and more efficacious in patients with moderate to severe disease or during flares. OTC agents are best used for maintenance between flares and to prevent progression of mild disease. Alternative and complementary treatments lack strong efficacy evidence. However, wet wraps, bleach baths, and other treatments appear to be promising when used in conjunction with conventional treatments. With the financial burden of atopic dermatitis ranging from 364 million to 3.8 billion dollars each year in the United States, we suspect this topic will gain further research attention.


Subject(s)
Dermatitis, Atopic , Histamine Antagonists , Nonprescription Drugs , Humans , Adrenal Cortex Hormones/therapeutic use , Dermatitis, Atopic/drug therapy , Emollients/therapeutic use , Histamine Antagonists/therapeutic use , Nonprescription Drugs/therapeutic use
5.
Adv Exp Med Biol ; 1447: 131-138, 2024.
Article in English | MEDLINE | ID: mdl-38724790

ABSTRACT

The treatment of atopic dermatitis (AD) with oral treatments has been limited in the past due to the increased risk of adverse effects associated with oral agents. However, in recent years, a shift toward the minimization of adverse effects has been explored. Although existing treatment options like oral corticosteroids and Immunosuppressive therapies have been utilized for acute flare-ups of AD, their long-term use is limited by adverse effects and the need for lab monitoring. New systemic treatment options such as Janus kinase (JAK) inhibitors are emerging as a promising therapy, due to their quick onset and antipruritic features. However, the black box warning associated with this medication class requires careful selection of appropriate candidates and patient education despite early favorable safety profiles seen in AD trials. Discussion of other oral agents, like antibiotics and antihistamines, and their role in AD management are also clarified.


Subject(s)
Dermatitis, Atopic , Humans , Administration, Oral , Dermatitis, Atopic/drug therapy , Histamine Antagonists/therapeutic use , Histamine Antagonists/adverse effects , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Janus Kinase Inhibitors/adverse effects , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/adverse effects
6.
J Chromatogr A ; 1727: 464989, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38763085

ABSTRACT

Ultrahigh-performance liquid chromatography coupled with high-field quadrupole Orbitrap high resolution mass spectrometry was used for the separation and determination of 20 antihistamines, and a dispersive micro solid-phase extraction procedure using high-performance absorbing material was developed as a sample preparation strategy for extracting 20 antihistamines from milk. Instrument conditions and key parameters influencing extraction efficiency were investigated to obtain an optimized method. The limit of detection for 20 antihistamines in milk using this method is 0.05 µg/L to 1.0 µg/L. Recoveries are between 80.7 % and 108.3 %, and the relative standard deviation is less than 15 %. It is suitable for confirmatory monitoring and quantitative analysis of 20 antihistamines in milk. The results show that antihistamines in milk may be noteworthy issues for human health and environmental pollution.


Subject(s)
Histamine Antagonists , Limit of Detection , Milk , Chromatography, High Pressure Liquid/methods , Milk/chemistry , Animals , Histamine Antagonists/analysis , Histamine Antagonists/isolation & purification , Solid Phase Microextraction/methods , Mass Spectrometry/methods , Cattle , Reproducibility of Results
7.
Adv Exp Med Biol ; 1447: 191-207, 2024.
Article in English | MEDLINE | ID: mdl-38724794

ABSTRACT

Atopic dermatitis has a substantial impact on sleep, appearance, psychological well-being, and other qualities of life. The visual appearance of lichenification, cheilitis, hyperpigmentation, ichthyosis, and erythema can be socially stigmatizing, and treatment of these symptoms is challenging. In managing pruritus in patients, practitioners should assess and document pruritus through questionnaires at each routine visit. Initially, practitioners should advise patients to employ nonpharmaceutical treatments such as emollients with wet wraps, elimination of triggers, changing scratching habits, and psychological interventions. If these methods of treatment are not successful or if the disease presentation is severe, pharmacological therapies should be employed. This chapter describes the therapeutic ladder for pruritus in atopic dermatitis and discusses each treatment modality in further detail for practitioners to advise their patients.First-line topical pharmaceutical agents include topical glucocorticoids and topical calcineurin inhibitors. Second-line topical agents include coal tar, menthol, capsaicin, or doxepin. After the use of topical agents has been exhausted, primary systemic agents can be applied. These include sedating antihistamines, nonsedating antihistamines, oral glucocorticoids, or cyclosporine A. Finally, neuromodulating or immunomodulating agents can be attempted, including SSRI/SNRIs, TCAs, immunosuppressants, neural modulators, and opioid receptor modulators. Outside of pharmacological treatments, phototherapy has been shown to provide a dramatic improvement of pruritus in atopic dermatitis and can be used at any stage of treatment including as a first-line agent.


Subject(s)
Dermatitis, Atopic , Pruritus , Humans , Antipruritics/therapeutic use , Calcineurin Inhibitors/therapeutic use , Dermatitis, Atopic/therapy , Dermatitis, Atopic/complications , Glucocorticoids/therapeutic use , Histamine Antagonists/therapeutic use , Phototherapy/methods , Pruritus/therapy , Pruritus/etiology , Pruritus/physiopathology , Pruritus/drug therapy
8.
Med Clin North Am ; 108(4): 609-628, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38816106

ABSTRACT

Allergic rhinitis is a common ailment in primary and acute care settings. Diagnosis is clinical, by means of history and physical examination. Referral to an allergist is considered when symptoms are difficult to manage and/or confirmation by means of further testing is desired. Management of allergic rhinitis should not be considered trivial, as multiple secondary effects can present as the course progresses. Several treatment modalities exist but should begin with glucocorticoid nasal sprays and systemic second- or third-generation antihistamines.


Subject(s)
Glucocorticoids , Histamine Antagonists , Rhinitis, Allergic , Humans , Rhinitis, Allergic/diagnosis , Rhinitis, Allergic/therapy , Rhinitis, Allergic/drug therapy , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosage , Histamine Antagonists/therapeutic use
9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(2): 175-181, 2024 Feb 28.
Article in English, Chinese | MEDLINE | ID: mdl-38755713

ABSTRACT

OBJECTIVES: Chronic urticaria presents a chronic process of recurrent attacks, and its first-line treatment is second-generation antihistamine with limited treatment options. The efficacy of antihistamine varies among individuals and cannot meet the needs of all patients. This study aims to explore the clinical efficacy and safety of Zhiyang Xiaozhen granules combined with antihistamine in the treatment of chronic urticaria patients. METHODS: We retrospectively analyzed the clinical data of patients with chronic urticaria who visited the Xiangya Hospital of Central South University from April 2020 to March 2021. The patients who received conventional second-generation antihistamine treatment were selected as a control group, while the patients who received combined treatment with Zhiyang Xiaozhen granules on the basis of conventional second-generation antihistamine treatment were selected as an observation group. The differences in the Weekly Urticaria Activity Score (UAS7) and Dermatology Life Quality Index (DLQI) between the 2 groups before and 4 weeks after treatment were compared. The Symptom Score Reduce Index (SSRI) was used to evaluate and compare the efficacy of the 2 treatment regimens. RESULTS: After 4 weeks of treatment, the UAS7 levels in both groups were significantly reduced (P=0.001 and P<0.001, respectively). The effective rates of the control group and the observation group were 61.11% and 59.38%, respectively when converting UAS7 to SSRI for efficacy evaluation, and there was no statistically significant difference in efficacy between the 2 groups (P>0.05); however, when converting DLQI to SSRI for efficacy evaluation, the effective rates of the control group and the observation group were 33.33% and 46.88%, respectively, and the difference in efficacy between the 2 groups was statistically significant (P<0.001). There were 3 patients with adverse drug reactions related to drowsiness in both groups. CONCLUSIONS: The combination of Zhiyang Xiaozhen granules and second-generation antihistamine can effectively improve disease activity in patients with chronic urticaria, and the improvement in quality of life is better than that with the second-generation antihistamine alone.


Subject(s)
Chronic Urticaria , Drugs, Chinese Herbal , Quality of Life , Humans , Chronic Urticaria/drug therapy , Drugs, Chinese Herbal/therapeutic use , Retrospective Studies , Female , Male , Treatment Outcome , Drug Therapy, Combination , Histamine Antagonists/therapeutic use , Adult
10.
Dalton Trans ; 53(24): 10126-10141, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38817206

ABSTRACT

Bilastine (BLA), 2-(4-(2-(4-(1-(2-ethoxyethyl)-1H-benzo[d]imidazole-2-yl)-piperidin-1-yl)-ethyl)-phenyl)-2-methylpropanoic acid, is an active antihistamine drug. With the idea of repurposing drugs from the existing pool of 'active' pharmaceutical ingredients, the therapeutic potency of bilastine as an anticancer agent was investigated via the tailored synthesis of a metal-based anticancer drug formulation of the type [BLA(phen)2M(II)]+·X-, where M = Co, Cu, and Zn and X- = NO3 and ClO4. The synthesized metal-based chemotherapeutics derived from the bilastine drug that acts as a ligand were thoroughly characterized using spectroscopic techniques, namely, UV-vis, FT-IR, and EPR (in the case of 1 and 2); 1H-NMR and 13C-NMR (in the case of 3); ESI-MS and single-crystal X-ray diffraction studies. Comprehensive biological studies (DNA binding, cleavage, and cytotoxic activity) using various biophysical and gel electrophoretic methods were carried out to validate their potential as anticancer agents. The cytotoxic activity of 'therapeutically promising' copper(II)-based drug candidate 2 was evaluated against MCF-7, MBA-MD-231, HeLa, HepG2, and Mia-PaCa-2 cancer cells via an SRB assay, and the results demonstrated 2 as a potent anticancer agent at low nanomolar concentrations against all tested cancer cells, preferably with a much superior anticancer efficacy against human pancreatic cancer cells.


Subject(s)
Antineoplastic Agents , Cobalt , Coordination Complexes , Copper , Drug Repositioning , Zinc , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Copper/chemistry , Copper/pharmacology , Zinc/chemistry , Zinc/pharmacology , Crystallography, X-Ray , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Cobalt/chemistry , Cobalt/pharmacology , Models, Molecular , Cell Line, Tumor , Cell Proliferation/drug effects , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Benzimidazoles/chemical synthesis , Drug Screening Assays, Antitumor , Molecular Structure , Piperidines/chemistry , Piperidines/pharmacology , Drug Resistance, Neoplasm/drug effects , Cell Survival/drug effects , Histamine Antagonists/chemistry , Histamine Antagonists/pharmacology , Histamine Antagonists/chemical synthesis
11.
Rev Med Suisse ; 20(868): 711-719, 2024 Apr 03.
Article in French | MEDLINE | ID: mdl-38568065

ABSTRACT

Histamine is responsible for many processes mediated by different receptors expressed on a variety of cells. The discovery of the first H1 antihistamines in the 1940s led to the development of numerous H1 and H2 antagonists with a broad application in many indications. The recent identification of two new histamine receptors (H3, H4) in the 1980s and 2000s led to the market authorization in Switzerland of new drugs since 2018. The purpose of this review is to provide a brief overview of the physiology of histamine, the recent development of new compounds in this field, antihistamine drug indications and relevant side effects.


L'histamine possède de nombreuses propriétés physiologiques, tant centrales que périphériques, via son action sur différents récepteurs. La découverte des premiers antihistaminiques H1 dans les années 1940 stimula le développement de nombreux autres antagonistes H1, puis H2, utilisés dans diverses spécialités médicales. L'identification plus récente de deux récepteurs à l'histamine (H3, H4) dans les années 1980 et 2000 relança le développement de nouveaux composés avec, en Suisse, une première autorisation de mise sur le marché en 2018. L'objectif de cet article de revue est de présenter brièvement la physiologie de l'histamine, l'histoire du développement des antihistaminiques, leurs utilisations actuelles, ainsi que leurs effets indésirables notables.


Subject(s)
Histamine Antagonists , Histamine , Humans , Histamine Antagonists/adverse effects , Narration , Switzerland
12.
PLoS One ; 19(4): e0297839, 2024.
Article in English | MEDLINE | ID: mdl-38603736

ABSTRACT

Herbal medicine is popularly used among patients who suffer from allergic rhinitis. This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of single medicinal plants in the management of allergic rhinitis. We searched MEDLINE, CENTRAL, and Web of Science for randomised controlled trials which evaluated the use of single medicinal plant for allergic rhinitis among adults and children. Twenty-nine randomised controlled trials (n = 1879) were eligible while 27 (n = 1769) contributed data for meta-analyses. Most studies (studies = 20) compared medicinal plants against placebo and Petasites hybridus was most frequently investigated (studies = 5). Very-low-to-low-certainty evidence suggests that compared to placebo, single medicinal plants may improve overall total nasal symptoms (SMD -0.31, 95% CI -0.59 to -0.02; participants = 249; studies = 5; I2 = 21%) especially nasal congestion and sneezing; and rhinoconjunctivitis quality of life (RQLQ) scores (MD -0.46, 95% CI -0.84 to -0.07; participants = 148; studies = 3; I2 = 0%). Moderate-certainty evidence show no clear differences between single medicinal plants and antihistamine in overall symptoms (Total nasal symptoms: SMD -0.14, 95% CI -0.46 to 0.18; participants = 149; studies = 2; I2 = 0%). As adjunctive therapy, moderate-certainty evidence shows that medicinal plants improved SNOT-22 scores when given as intranasal treatment (MD -7.47, 95% CI -10.75 to -4.18; participants = 124; studies = 2; I2 = 21%). Risk of bias domains were low or not clearly reported in most studies while heterogeneity was substantial in most pooled outcomes. Route of administration and age were identified to be plausible source of heterogeneity for certain outcomes. Medicinal plants appear to be well tolerated up to 8 weeks of use. Clear beneficial evidence of medicinal plants for allergic rhinitis is still lacking. There is a need for improved reporting of herbal trials to allow for critical assessment of the effects of each individual medicinal plant preparation in well-designed future clinical studies.


Subject(s)
Plants, Medicinal , Rhinitis, Allergic , Adult , Child , Humans , Quality of Life , Rhinitis, Allergic/drug therapy , Administration, Intranasal , Histamine Antagonists
13.
Anal Chem ; 96(17): 6599-6608, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38640514

ABSTRACT

Antihistamines relieve allergic symptoms by inhibiting the action of histamine. Further understanding of antihistamine transmembrane mechanisms and optimizing the selectivity and real-time monitoring capabilities of drug sensors is necessary. In this study, a micrometer liquid/liquid (L/L) interfacial sensor has served as a biomimetic membrane to investigate the mechanism of interfacial transfer of five antihistamines, i.e., clemastine (CLE), cyproheptadine (CYP), epinastine (EPI), desloratadine (DSL), and cetirizine (CET), and realize the real-time determinations. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques have been used to uncover the electrochemical transfer behavior of the five antihistamines at the L/L interface. Additionally, finite element simulations (FEMs) have been employed to reveal the thermodynamics and kinetics of the process. Visualization of antihistamine partitioning in two phases at different pH values can be realized by ion partition diagrams (IPDs). The IPDs also reveal the transfer mechanism at the L/L interface and provide effective lipophilicity at different pH values. Real-time determinations of these antihistamines have been achieved through potentiostatic chronoamperometry (I-t), exhibiting good selectivity with the addition of nine common organic or inorganic compounds in living organisms and revealing the potential for in vivo pharmacokinetics. Besides providing a satisfactory surrogate for studying the transmembrane mechanism of antihistamines, this work also sheds light on micro- and nano L/L interfacial sensors for in vivo analysis of pharmacokinetics at a single-cell or single-organelle level.


Subject(s)
Cetirizine , Clemastine , Cyproheptadine , Imidazoles , Loratadine , Loratadine/analogs & derivatives , Loratadine/pharmacology , Loratadine/analysis , Loratadine/chemistry , Cyproheptadine/pharmacology , Cyproheptadine/analogs & derivatives , Cyproheptadine/analysis , Cetirizine/analysis , Cetirizine/pharmacology , Cetirizine/chemistry , Clemastine/analysis , Clemastine/pharmacology , Clemastine/metabolism , Histamine Antagonists/pharmacology , Histamine Antagonists/chemistry , Histamine Antagonists/analysis , Histamine Antagonists/metabolism , Electrochemical Techniques/methods , Biomimetics , Dibenzazepines/pharmacology , Dibenzazepines/chemistry
14.
Eur J Dermatol ; 34(1): 3-12, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38557452

ABSTRACT

Chronic spontaneous urticaria (CSU) is a relatively common dermatological disorder characterized by sudden and unpredictable onset of pruritic wheals and/or angioedema, for more than six weeks. It is a mast cell-mediated histaminergic disorder, considerably worsening patients' quality of life. Current treatment options include anti-histamines, omalizumab and cyclosporine, in a step-wise algorithmic approach, aimed at complete symptom control. Patients do not respond uniformly to these therapeutic options due to phenotypic and endotypic heterogeneity, and often remain uncontrolled/poorly controlled. Recent research is focused on identifying certain biomarkers to predict therapeutic response and facilitate patient-targeted personalized treatment, for maximum benefit. The current article summarizes various biomarkers explored to date, and also elaborates their role in predicting therapeutic response to anti-histamines, omalizumab and cyclosporine, in CSU patients. High disease activity, elevated CRP/ESR and elevated D-dimer are the most important predictors of non/poor-response to antihistamines. Low and very low baseline IgE, elevated CRP/ESR, ASST+, BAT/BHRA+, basopenia, eosinopenia, and elevated D-dimer are predictors of poor and good response to omalizumab and cyclosporine, respectively. Additionally, normal or slightly elevated baseline IgE and FceR1 overexpression are predictors of a faster response with omalizumab. However, none of these predictors have so far been completely validated and are not yet recommended for routine use. Thus, large-scale prospective studies are needed to confirm these predictive biomarkers and identify new ones to achieve the goal of personalized medicine for CSU.


Subject(s)
Anti-Allergic Agents , Chronic Urticaria , Urticaria , Humans , Omalizumab/therapeutic use , Quality of Life , Chronic Disease , Chronic Urticaria/drug therapy , Urticaria/drug therapy , Urticaria/diagnosis , Histamine Antagonists/therapeutic use , Biomarkers , Cyclosporine/therapeutic use , Immunoglobulin E , Anti-Allergic Agents/therapeutic use , Treatment Outcome
15.
Bioorg Chem ; 147: 107387, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38643561

ABSTRACT

Histamine 4 receptor (H4R), the most recently identified subtype of histamine receptor, primarily induces inflammatory reactions upon activation. Several H4R antagonists have been developed for the treatment of inflammatory bowel disease (IBD) and atopic dermatitis (AD), but their use has been limited by adverse side effects, such as a short half-life and toxicity. Natural products, as an important source of anti-inflammatory agents, offer minimal side effects and reduced toxicity. This work aimed to identify novel H4R antagonists from natural products. An H4R target-pathway model deconvoluted downstream Gi and MAPK signaling pathways was established utilizing cellular label-free integrative pharmacology (CLIP), on which 148 natural products were screened. Cryptotanshinone was identified as selective H4R antagonist, with an IC50 value of 11.68 ± 1.30 µM, which was verified with Fluorescence Imaging Plate Reader (FLIPR) and Cellular Thermal Shift (CTS) assays. The kinetic binding profile revealed the noncompetitive antagonistic property of cryptotanshinone. Two allosteric binding sites of H4R were predicted using SiteMap, Fpocket and CavityPlus. Subsequent molecular docking and dynamics simulation indicated that cryptotanshinone interacts with H4R at a pocket formed by the outward interfaces between TM3/4/5, potentially representing a new allosteric binding site for H4R. Overall, this study introduced cryptotanshinone as a novel H4R antagonist, offering promise as a new hit for drug design of H4R antagonist. Additionally, this study provided a novel screening model for the discovery of H4R antagonists.


Subject(s)
Biological Products , Dose-Response Relationship, Drug , Drug Discovery , Receptors, Histamine H4 , Humans , Biological Products/chemistry , Biological Products/pharmacology , Receptors, Histamine H4/antagonists & inhibitors , Receptors, Histamine H4/metabolism , Structure-Activity Relationship , Molecular Structure , Phenanthrenes/pharmacology , Phenanthrenes/chemistry , Histamine Antagonists/pharmacology , Histamine Antagonists/chemistry , Molecular Docking Simulation , Phenotype
16.
Expert Opin Pharmacother ; 25(5): 551-569, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38654448

ABSTRACT

INTRODUCTION: Urticaria, a mast cell-mediated skin disease, manifests as acute or chronic, with the latter divided into spontaneous and inducible types and requires individualized management, including identifying triggers and comorbidities. Antihistamines, particularly the second generation group, form the mainstay of primary treatment plans consisting of dosage adjustments and/or in combination with other treatment modalities depending on underlying disease control. AREAS COVERED: A literature search was conducted using 'antihistamines,' 'urticaria,' 'pharmacogenomics,' 'genomics,' 'biomarkers' and 'treatment response' as key words. In this review, we focus on the comprehensive understanding and application of antihistamines in managing adult and adolescent patients with chronic urticaria. EXPERT OPINION: Using antihistamines to treat urticaria is set to change significantly, focusing more on personalized medicine and identifying key biomarkers to enhance treatment response prediction. These changes aim to make treatments more specific and cost-effective by avoiding unnecessary tests. Applying new approaches in everyday clinical care faces challenges like proving the biomarkers' reliability, updating current guidelines, and incorporating individualized treatments into standard procedures. Efforts should now concentrate on finding easy-to-use biomarkers, improving access to pharmacogenomics, understanding why some patients are resistant to treatment, and creating more specific treatment options based on patient needs.


Subject(s)
Chronic Urticaria , Histamine Antagonists , Precision Medicine , Humans , Chronic Urticaria/drug therapy , Precision Medicine/methods , Histamine Antagonists/therapeutic use , Adolescent , Adult , Biomarkers , Pharmacogenetics , Cost-Benefit Analysis , Dose-Response Relationship, Drug
17.
Int J Pharm ; 655: 124033, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38522490

ABSTRACT

The incorporation of polymers into drug delivery vehicles has been shown to be a useful approach to prolong the residence time of drugs in the precorneal tear film and to improve penetration into biological membranes. The main objective of this research was to formulate novel viscous eye drops with ketotifen as the active ingredient, containing the polysaccharides: chitosan (MCH), hydroxypropyl guar gum (HPG) and hyaluronic acid (SH) alone and in combination as functional polymers. DSC and FT-IR techniques showed the compatibility between ketotifen and polymers. Physicochemical and rheological analysis at ambient and simulated physiological conditions, as well as the evaluation of mucoadhesive properties showed that vehicles containing combinations of polymers have suitable physicochemical and functional properties with demonstrated synergism between combined polymers (MCH and HPG i.e. SH and HPG). The drug permeability was successfully estimated in vitro using HCE-T cell-based models. MTT cytotoxicity assay demonstrates that the tested formulations were non-toxic and well tolerated. In vivo preclinical study on mice revealed that both vehicles containing mixed polymers enhanced and prolonged the antipruritic/analgesic-like effect of ophthalmic ketotifen. Based on these results, both combinations of polysaccharide polymers, especially SH-HPG, could be considered as potential new carriers for ketotifen for ophthalmic use.


Subject(s)
Ketotifen , Polymers , Animals , Mice , Ketotifen/adverse effects , Ophthalmic Solutions/chemistry , Spectroscopy, Fourier Transform Infrared , Polysaccharides/chemistry , Histamine Antagonists
18.
Biochem Pharmacol ; 223: 116164, 2024 May.
Article in English | MEDLINE | ID: mdl-38531422

ABSTRACT

Cancer morbimortality is still a great concern despite advances in research and therapies. Histamine and its receptors' ligands can modulate different biological responses according to the cell type and the receptor subtype involved. Besides the wide variety of histamine functions in normal tissues, diverse roles in the acquisition of hallmarks of cancer such as sustained proliferative signaling, resistance to cell death, angiogenesis, metastasis, altered immunity and modified microenvironment have been described. This review summarizes the present knowledge of the various roles of histamine H2 receptor (H2R) ligands in neoplasias. A bioinformatic analysis of human tumors showed dissimilar results in the expression of the H2R gene according to tumor type when comparing malignant versus normal tissues. As well, the relationship between patients' survival parameters and H2R gene expression levels also varied, signaling important divergences in the role of H2R in neoplastic progression in different cancer types. Revised experimental evidence showed multiple effects of H2R antihistamines on several of the cited hallmarks of cancer. Interventional and retrospective clinical studies evaluated different H2R antihistamines in cancer patients with two main adjuvant uses: improving antitumor efficacy (which includes regulation of immune response) and preventing toxic adverse effects produced by chemo or radiotherapy. While there is a long path to go, research on H2R antihistamines may provide new opportunities for developing more refined combination therapeutic strategies for certain cancer types to improve patients' survival and health-related quality of life.


Subject(s)
Histamine , Neoplasms , Humans , Histamine/metabolism , Retrospective Studies , Quality of Life , Histamine H2 Antagonists , Histamine Antagonists/pharmacology , Histamine Antagonists/therapeutic use , Receptors, Histamine H2/genetics , Receptors, Histamine H2/metabolism , Neoplasms/drug therapy , Tumor Microenvironment
19.
Environ Sci Technol ; 58(12): 5512-5523, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38478581

ABSTRACT

The investigation of pharmaceuticals as emerging contaminants in marine biota has been insufficient. In this study, we examined the presence of 51 pharmaceuticals in edible oysters along the coasts of the East and South China Seas. Only nine pharmaceuticals were detected. The mean concentrations of all measured pharmaceuticals in oysters per site ranged from 0.804 to 15.1 ng g-1 of dry weight, with antihistamines being the most common. Brompheniramine and promethazine were identified in biota samples for the first time. Although no significant health risks to humans were identified through consumption of oysters, 100-1000 times higher health risks were observed for wildlife like water birds, seasnails, and starfishes. Specifically, sea snails that primarily feed on oysters were found to be at risk of exposure to ciprofloxacin, brompheniramine, and promethazine. These high risks could be attributed to the monotonous diet habits and relatively limited food sources of these organisms. Furthermore, taking chirality into consideration, chlorpheniramine in the oysters was enriched by the S-enantiomer, with a relative potency 1.1-1.3 times higher when chlorpheniramine was considered as a racemate. Overall, this study highlights the prevalence of antihistamines in seafood and underscores the importance of studying enantioselectivities of pharmaceuticals in health risk assessments.


Subject(s)
Environmental Monitoring , Ostreidae , Pharmaceutical Preparations , Water Pollutants, Chemical , Animals , Humans , Brompheniramine/analysis , China , Chlorpheniramine/analysis , Histamine Antagonists/analysis , Oceans and Seas , Ostreidae/chemistry , Pharmaceutical Preparations/analysis , Promethazine/analysis , Water Pollutants, Chemical/analysis
20.
JAMA ; 331(10): 866-877, 2024 03 12.
Article in English | MEDLINE | ID: mdl-38470381

ABSTRACT

Importance: Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations: Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance: Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.


Subject(s)
Glucocorticoids , Histamine Antagonists , Rhinitis, Allergic , Humans , Budesonide/administration & dosage , Budesonide/therapeutic use , Cetirizine/therapeutic use , Fluticasone/administration & dosage , Fluticasone/therapeutic use , Histamine H1 Antagonists/administration & dosage , Histamine H1 Antagonists/therapeutic use , Immunoglobulin E/immunology , Mometasone Furoate/administration & dosage , Mometasone Furoate/therapeutic use , Olopatadine Hydrochloride/administration & dosage , Olopatadine Hydrochloride/therapeutic use , Pruritus/etiology , Rhinitis, Allergic/complications , Rhinitis, Allergic/diagnosis , Rhinitis, Allergic/immunology , Rhinitis, Allergic/therapy , Rhinorrhea/etiology , Sneezing , Triamcinolone/administration & dosage , Triamcinolone/therapeutic use , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Rhinitis/drug therapy , Histamine Antagonists/administration & dosage , Histamine Antagonists/therapeutic use , Administration, Intranasal
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