Antihistamines Research Articles

Histamine deficiency exacerbates cisplatin-induced ferroptosis in cochlea hair cells of HDC knockout mice

Cisplatin (CDDP) is extensively utilized in the management of diverse types of cancers, but its ototoxicity cannot be ignored, and clinical interventions are not ideal. Histidine decarboxylase (HDC) is the exclusive enzyme for histamine synthesis. Anti-histamine receptor drugs are ubiquitously employed in the therapeutics of allergies and gastrointestinal diseases. Yet, the specific role of histamine and its signaling in the inner ear is not fully understood. This study utilized cisplatin treated mice and HEI-OC1 auditory hair cell line to establish a cisplatin-induced ototoxicity (CIO) model. Histidine decarboxylase knockout (HDC−/−) mice and histamine receptor 1 (H1R) antagonist were utilized to investigate the influence of HDC/histamine/H1R signaling on ototoxicity. The results identified HDC and H1R expression in mouse hair cells. Transcriptomics indicated that the expression levels of oxidative stress-related genes in the cochlea of HDC−/− mice increased. Furthermore, histamine deficiency or suppression of H1R signaling accelerated HC ferroptosis, a pivotal factor underlying the aggravation of CIO in vivo and in vitro, conversely, the supplementation of exogenous histamine reversed these deleterious effects. Mechanistically, this study revealed that the malfunction of HDC/histamine/H1R signaling induced upregulation of NRF2 expression, accompanied by the upregulation of ACSL4 and downregulation of GPX4 expression, which are major regulatory factors of ferroptosis. In summary, histamine deficiency may induce hair cell death by regulating the H1R pathway and exacerbate CIO. Our findings have indicated a potential therapeutic target for CIO.

The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2.

Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19.

A highly sensitive spectrofluorimetric method for the determination of bilastine in human plasma: Application of content uniformity testing.

Bilastine, a new second generation antihistaminic drug, has been widely used for relieving symptoms of allergic rhinitis and urticaria without a sedative effect. A simple, cost-effective, and highly sensitive fluorimetric method was developed for the estimation of bilastine in human plasma, in addition to its pure state and tablets. The suggested method depended on binary complex formation of eosin with bilastine in a buffered medium at pH 4.2. The formed complex resulted in quantitative quenching of eosin emission at 538 nm after excitation at 335 nm. This method demonstrates a broad range of linearity, spanning from 200 to 1000 ng/mL, and exhibits exceptional sensitivity, with a limit of detection and quantitation of 30.85 and 93.48 ng/mL, respectively. In addition, this spectrofluorimetric method may be employed to determine the amount of bilastine in human plasma and tablets with satisfactory accuracy and excellent precision. Furthermore, the content uniformity of bilastine in commercially available tablets was successfully tested by this approach. Compared with the reference method, there were no significant variations in terms of precision or accuracy. In conclusion, the proposed protocol is highly recommended to quantitatively estimate bilastine in different quality control settings.

Green and sensitive detection of olopatadine in aqueous humor using a signal-on fluorimetric approach: GREEnness assessment.

Olopatadine (OLP) is widely utilized as an effective antihistaminic drug for alleviating ocular itching associated with allergic conjunctivitis. With its frequent usage in pharmacies, there arises a pressing need for a cost-effective, easily implementable, environmentally sustainable detection method with high sensitivity. This study presents a novel signal-on fluorimetric method for detecting OLP in both its pure form and aqueous humor. The proposed approach depends on enhancing the weak intrinsic fluorescence emission of OLP, achieving a remarkable increase of up to 680% compared to its intrinsic fluorescence. This enhancement is achieved by forming micelles around protonated OLP using an acetate buffer (pH 3.6) and incorporating a solution of sodium dodecyl sulfate (SDS) surfactant. A strong correlation (R = 0.9996) is observed between the concentration of OLP and fluorescence intensities ranging from 1.0 to 100.0 ng mL-1 with a limit of detection of 0.22 ng mL-1. This described method is successfully employed for quantifying OLP in both its powder form and pharmaceutical eye drops. Furthermore, it demonstrates robust performance in determining OLP in artificial aqueous humor with a percentage recovery of 99.05 ± 1.51, with minimal interference from matrix interferents. Moreover, the greenness of the described method was evaluated.

Cumulative Dose Effects of H1 Antihistamine Use on the Risk of Dementia in Patients With Allergic Rhinitis

H1 antihistamines (AHs), categorized as first-generation antihistamines (FGAs) or second-generation antihistamines (SGAs), possess anticholinergic properties linked to heightened dementia risk. To explore dementia risk in patients with allergic rhinitis using AHs. Taiwanese patients with new-onsetallergic rhinitis (2011-2017) constituted the study population (677,971 with FGAs or SGAs, 36,081 without AHs). AH use was measured in cumulative defined daily dose (cDDD). Patients were grouped by cDDD (nonuser, <60 cDDD, 60-120 cDDD, and >120 cDDD). A Cox proportional hazard model assessed the AH-dementia association. Sensitivity analysis explored AH effects on dementia risk across subgroups and associations between specific AHs and dementia types. FGAs in patients with allergic rhinitis were associated with elevated dementia risk. At less than 60 cDDD, adjusted hazard ratio (aHR) was 1.13 (95% CI, 1.09-1.17); at 60 to 120 cDDD, aHR was 1.29 (95% CI, 1.21-1.38); and at more than 120 cDDD, aHR was 1.51 (95% CI, 1.42-1.62). SGAs also raised dementia risk. At less than 60 cDDD, aHR was 1.11 (95% CI, 1.05-1.17); at 60 to 120 cDDD, aHR was 1.19 (95% CI, 1.12-1.26); and at more than 120 cDDD, aHR was 1.26 (95% CI, 1.19-1.33). Patients with allergic rhinitis on FGAs or SGAs face an escalating dementia risk with increasing cumulative dosage. Moreover, FGAs exhibit a higher dementia risk compared with SGAs. Nevertheless, extensive clinical trials are imperative for confirming the association between FGA use, SGA use, and dementia risk.

Efficacy and safety of combinations of H1 antihistamines in the treatment of urticaria: A scoping review.

The efficacy and safety of combining H1 antihistamines (AHs) for treating urticaria are currently unclear. This scoping review aims to provide a comprehensive overview of the evidence regarding the efficacy and safety of H1 AH combinations in the management of urticaria up to May 2023. The search encompassed databases such as PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and the China Biological Medicine Database. The inclusion criteria comprised randomised controlled trials (RCTs), non-randomised trials (NRTs), case reports, and case series focusing on urticaria treatment. Initially screening 12,887 studies, this review ultimately selected 109 studies involving 11,435 patients. These studies documented 43 different combination treatments across 11 types of urticaria. In comparison to monotherapy, combination therapy exhibited superior efficacy in 94 studies that reported treatment efficacy. Regarding adverse drug reactions (ADRs), 67 studies disclosed ADR incidences, with combination therapy showing lower ADR rates in 32 studies. Additionally, 7 studies reported similar ADR rates between combination therapy and monotherapy with AHs. Common ADRs included symptoms such as drowsiness, nausea, fatigue, dry mouth, dizziness, and headache, while less frequent side effects encompassed hypotension, otitis media, polyuria, rhinorrhoea, abnormal liver function, and rash. ADR rates ranged from 0% to 21% in the treatment group, and from 0.5% to 75% in the control group. Importantly, patients generally tolerated these ADRs well, with symptoms resolving upon discontinuation of treatment. The study's findings suggest that combining AHs leads to enhanced efficacy and reduced safety risks compared to monotherapy in the context of urticaria treatment. These results advocate for considering combination therapy as a viable option in clinical practice, especially for chronic urticaria cases. Nonetheless, caution is advised, and close monitoring for potential ADRs is crucial during treatment.

Aquagenic Syringeal Acrokeratoderma: Case Report

Aquagenic syringeal acrokeratoderma is a rare, acquired and transient type of keratoderma that may occur after a few minutes of exposure to water, usually occurs in adolescents and young female adults and it is characterized by the sudden appearance of translucent papules that converge on the palms and occasionally on the soles, macerated and with accentuation of the finger lines. We present the case of a 36-year-old female, with a history of long evolution of contact dermatitis. She presented a dermatosis characterized by maceration, roughed skin with wrinkling appearance and slight desquamation especially over thenar area after contact with water for a few minutes. After received general skin care, second generation antihistamine drugs, and emollients with 10% urea for a week, she reports improvement of the lesions. Aquagenic acrokeratoderma is a rare disease that can adversely affect the patient's life quality, however the etiology and pathogenesis are not clear; until date, there is no consensus on clinical treatment; for this reason it’s important to identify the cases and report which treatments were effective, and achieve unifying the management of this pathology.

El pediatra de Atención Primaria y la rinitis alérgica

Allergic rhinitis (AR) is an inflammation of the nasal mucosa after exposure to an allergen in previously sensitized people. Characteristic symptoms include nasal itching, rhinorrhea, sneezing and nasal congestion, which may be accompanied by otic, pharyngeal and ocular symptoms (allergic rhinoconjunctivitis). AR has a great impact on quality of life and is considered undertreated and underdiagnosed. Dust mites and grass pollens are the most important allergens. The diagnosis is made through a detailed medical history that includes exposure to environmental triggers and the child's environment at the family, school, leisure and pet levels. It is advisable to perform an allergy study to identify allergic triggers, especially in case of persistent rhinitis. Treatment is based on the identification and elimination of specific allergens, when possible, and the use of stepwise medications that reduce symptoms. Nasal corticosteroids (NC) are part of the first line of treatment, their use being unavoidable in moderate-severe AR. When there is no adequate response to the initial treatment, combining antihistamine (AH) is indicated. Intranasal AH are more effective in improving nasal congestion than oral AH and have a faster onset of action than oral AH and NC, and are part of the first line of treatment in seasonal AR and intermittent AR. Immunotherapy will be used in selected patients who do not respond to other treatments.

Your New Head of the Undergraduate Medical School - An Introduction from Prof. Malcolm Shepherd

A long time ago….. and by a long time Imean before new Dr Who, before iPhonesand around the first appearance of StarWars Lego …… truly a very long time ago,things were simpler. Not necessarilybetter, different, much simpler….notclearly better, but definitely better!Conversations never ended, lasting longinto the night without conclusion; no onewas blessed with facts, just opinions andpassion. ‘Britain will remain at the centre ofEurope….’‘no way William Shatner (original CaptainKirk for non-geeks) will ever get intospace …’‘Glasgow could never host the biggestcycling event of all time…..’‘no, you could not possibly be allergic tored meat, you are made of red meat…’Of course now smartphones and theinternet have relegated the art ofconversation to a list of facts and dates,and no one speaks to each other without aseries of emojis and hand gestures. Or Imight have got that wrong you tell me…….‘But surely. Old man’ you say, carefullypicking the most contentious topic fromthe list above, Surely you cannot beallergic to red meat, we are all mammals,and the rules of Immunology say youcannot be immune to self.’‘Ah’ says the wise old man (In this scenariobizarrely that is me), ‘a long time ago youwould be correct, but in 2002 strangereports emerged that people with ahistory of tick bites, experiencedanaphylaxis after eating red meat’. Now across the world from Australia toNorth East USA the phenomenon of redmeat allergy causing strange delayedonset anaphylaxis, often as much as 4 hours after eating has been recognised.Breaking many rules of allergy fromrapid onset to variable presentation thestrangest aspect of this allergy is thatsensitisation seems to follow the bite ofparticular species of ticks. One of thoseticks is the indigenous Deer tick in theUK and so yes this allergy is found inrelatively high numbers in Scotland.Don’t worry, it is very very rare, but wehave identified around 40 patients whohave this allergy after being bitten byticks in Scotland.‘So what?’ you may say ‘its so rare whyshould we worry’. Well the truth is thattick populations are growing in the UK.There are a number of reasons, butglobal climate change with warmermoister winters probably play a part.Increased use of rural environmentswith Scotland’s amazing right to roamlegislation and wonderful landscapeincreases the exposure of urban andrural populations to ticks and we areseeing sufferers from all regions of thecountry. Climate change is an engine of change inhealth science and while self-allergymay seem a trivial example, it is a verypowerful concept; our immune systemsturning on ourselves in the face of awarming climate. Allergy medicine is fullof the human consequences of awarming climate from self-allergy topan-allergens crossing botanical speciesand we see new patterns of disease emerging from theenvironmental catastrophe we arefacing. Learning about the engines of change inmedicine and discovering what healthscience can do to limit our global impactwill become an increasingly importantaspect of Medicine as you becomeleaders and innovators of the future. Ihope we can inspire you to think aboutthe ways we can all work to limit this andavoid potential catastrophe.

Unveiling Treatment Response Predictors in Predominant Subtypes of Chronic Inducible Urticaria

Introduction: Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria (CU), which requires specific triggers to occur. Despite their common occurrence, treatment response rates and predictors of treatment responses are largely lacking in the literature. This study evaluates antihistamine (AH) and omalizumab response rates in the most common CIndU subtypes and examines whether certain features can predict treatment responses. Methods: We retrospectively analyzed CU patients with at least one CIndU subtype and performed comparisons between subgroups, in a total of 423 patients (70% CIndU, 30% chronic spontaneous urticaria [CSU] plus CIndU). Results: The treatment response rates in CIndU were 51.6%, 51.5%, and 86.5% with standard-dose second-generation H1-antihistamines (sgAHs), updosed/combined sgAH, and omalizumab, respectively. Overall AH response was higher in CIndU than CSU plus CIndU (78.3% vs. 62%, p = 0.002) and in symptomatic dermographism (SD) and cold urticaria (ColdU) than cholinergic urticaria (ChoU) (83.2% vs. 78.3 vs. 60.9%, p = 0.04). AH-refractory patients had a longer disease duration (45.2 ± 56.7 months vs. 37 ± 51.9 months, p = 0.04), more angioedema, accompanying CSU, mixed CIndU subtypes (37.5% vs. 21.1%, p = 0.003; 45.1% vs. 27.1%, p = 0.002; 8.8% vs. 2.4%, p = 0.014), and lower baseline urticaria control test scores (5.86 ± 3.3 vs. 8.6 ± 3.6, p < 0.001) than AH-responsive patients. Conclusion: CIndU exhibits a good response to both AHs and omalizumab. Notably, the response to AHs is more pronounced in SD and ColdU compared to ChoU. Disease duration, angioedema, accompanying CSU, mixed CIndU, and lower baseline UCT scores may be used to predict AH treatment outcome in CIndU.

Revolutionizing Pediatric Dermatology: Dupilumab’s Impact on Atopic Dermatitis in Kids

Eczema, or atopic dermatitis, is a common, non-communicable, immune-mediated, inflammatory skin illness mainly affecting children. It is a chronic condition. It causes mental health problems like anxiety, sadness, anxiety, depression, hyperactivity, and obesity. It is the first skin ailment and the fifteenth non-fatal disease. The purpose of the present research study was to evaluate the Safety and Effectiveness of biological treatment for atopic dermatitis using monoclonal antibodies against non-biological treatment, including antibiotics, immunosuppressants, demards, histamine antagonists and corticosteroids. Patient information was gathered from FDA-approved clinical trials. The comparative analysis found that Biological therapies like Dupilumab, Omalizumab, and Ustekinumab improve symptoms and disease control in atopic dermatitis. Non-biological treatments may not be as effective. Early antibiotic exposure can increase infection vulnerability. Mild eczema infections require biological agents. Topical corticosteroids can be combined with Dupilumab for effective treatment of atopic dermatitis. Studies show that Dupilumab improves symptoms and quality of life, making it a better option than a placebo. FDA recommends using biological agents over immunosuppressants in paediatrics for improved immune results. FDA clinical trials showed that dupilumab is a safe and effective treatment for children with moderate-to-severe atopic dermatitis, reducing disease severity and improving quality of life in young AD patients.

Safflower yellow in Carthami Flos is responsible for Xuebijing Injection-induced immediate hypersensitivity reaction through activating complement C3

ObjectiveXuebijing Injection (XBJI) is mainly used for treating sepsis in China, and even COVID-19 recently. This study aimed to clarify the molecular mechanism(s) and identify the potential “common culprit(s)” for XBJI-caused immediate hypersensitivity reaction (IHR) which is the main type of its adverse reactions. MethodsAntiserum against XBJI was prepared by intraperitoneal immunization in combination with aluminum adjuvant for five weeks. Antagonistic experiments were performed by using several antagonists against different mediators in Evans Blue leakage model. Propranolol-pretreated mice were used to determine the capacity of XBJI to trigger systemic IHR. Serum total IgE (tIgE) and mouse mast cell protease 1 (MCPT-1) levels, complement activation, and the levels of supernatant inflammatory mediators were determined by ELISAs. Lipopolysaccharide (LPS)-activated RAW264.7 macrophages were used for evaluating the anti-inflammatory activity of XBJI, while human mast cells (LAD2) were used for assessing the effect of XBJI on mast cell degranulation. ResultsContinuous treatment (i.p.) with XBJI along with aluminum adjuvant did not elevate the levels of serum tIgE and MCPT-1. In vitro, XBJI could not directly cause the degranulation of LAD2 cells. It induced a robust Evans Blue leakage after the first injection in mouse paw. Mechanism study demonstrated that antagonists for histamine H1/H2 receptors and complement C3a receptor counteracted XBJI-induced IHR. XBJI also directly activated complement C3 in human serum. Through screening five herbs of XBJI and the constituents, only safflower yellow (SY) in Carthami Flos was able to induce IHR. The discolored-XBJI not only did not induce IHR locally and systemically, but also could suppressing the production of proinflammatory mediators in LPS-activated RAW264.7 macrophages. ConclusionXBJI failed to induce immune IHR, but potently triggered non-immune IHR through direct activating complement C3 to provoke histamine release. SY in Carthami Flos was the underlying “common culprit” responsible for XBJI-caused IHR. The anti-inflammatory action of XBJI can be retained after decolorization. Our study provides a scientific basis for not only preventing and treating XBJI-caused IHR clinically, but also improving its production process.

Green HPLC–DAD method for the analysis of analgesic and antihistamine drugs adulterated in herbal mixtures

This study presents a HPLC-DAD method developed for the simultaneous detection of histamine H1 antagonist drugs and analgesic compounds, including paracetamol, cetirizine hydrochloride, cinnarizine, chlorpheniramine maleate, and loratadine, in herbal formulations. This method systematically investigates critical parameters for enhancing separation and quantification using HPLC-DAD. Chemometric techniques were employed to optimize the method for detecting adulterants, with sample preparation involving liquid-phase extraction and a mobile phase for separation using HPLC-DAD. The calibration curves were linear over concentrations ranging from 10 to 40 µg/mL, with correlation coefficients exceeding 0.99. The method exhibits good accuracy, with mean recoveries ranging from 90 to 105 %, and precision (% RSD) for intraday and interday precision: 0.71 to 2.94 %. The limits of detection (LODs) and limits of quantification (LOQs) for each compound are provided. The HPLC-DAD method ensures rigorous quality control, detecting potential adulteration in 32 traditional medicine samples and emphasizing its safety and efficacy in managing allergic conditions. The proposed approach is considered environmentally friendly based on evaluations from commonly used greenness assessment tools, Green analytical chemistry metrics (ComplexGAPI, AGREE, BAGI) confirm the method's sustainability and practicality.

Design of resonance Rayleigh scattering and spectrofluorimetric methods for the determination of the antihistaminic drug, hydroxyzine, based on its interaction with 2,4,5,7-tetraiodofluorescein: Evaluation of analytical eco-scale and greenness/whiteness algorithms.

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 551.5nm (excitation = 527.5nm) 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 0.15-1.5μg ml-1 and 0.1-1.2μg 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.

Effects of diphenhydramine exposure on reproduction of mature Japanese medaka (Oryzias latipes)

Diphenhydramine (DPH) is an antihistamine drug. It has been frequently detected in the environment, because it is not completely degraded in wastewater treatment plants. Recent studies have shown the adverse effects of DPH exposure to various aquatic organisms; however, its chronic effects on fish have been poorly elucidated. In this study, several pairs of mature Japanese medaka (Oryzias latipes) were exposed to DPH for a long period to determine the effects of DPH exposure on the subsequent generations, number of spawned and fertilized eggs, expression of sex-related genes, feeding behavior, embryo development, hatching rate, malformations among the hatched larvae, and mortality rate. The number of spawned eggs significantly decreased, when the parent fish were continuously exposed to 31.6 μg/L DPH for over 46 days. DPH exposure also altered the feeding behavior of medaka individuals, and increased the larval mortality rate. The effects of DPH exposure to fish may occur to some extent in the actual aquatic environment, although the risk evaluations in the field are limited.

Disease burden and unmet need for acute allergic reactions – A patient perspective

BackgroundAcute allergic reactions (AARs) occur shortly after exposure to an allergen, and the severity is on a continuum. Systemic corticosteroids (CS) are mainstay treatment of moderate to severe AARs, whereas those at risk of the most severe AARs (ie, anaphylaxis) are also recommended prescription of epinephrine autoinjectors. There is limited research on the impact of AARs not fulfilling the criteria for anaphylaxis. We have characterized a sample with a history of moderate to severe AARs and evaluated their self-reported disease burden (ie, daily life impact, anxiety, and treatment impediments). MethodsSurvey study of adults with experience of AARs treated with CS. Participants recruited from a web-based panel and using social media were asked to complete a questionnaire related to their allergy and experience of AARs. The results were summarized for the whole sample and across subgroups with and without prescription of epinephrine. ResultsThe final study sample included 387 participants (80% women, mean age 41), of which 129 (33%) had at some point been prescribed epinephrine. The most common symptoms were respiratory (80%) and skin (78%) manifestations, and the mean (standard deviation, SD) self-rated severity score (scale from 0 [very mild] to 10 [very severe]) of the most recent AAR was 6.1 (2.0). More than 80% had experience of AARs interrupting daily activities and 50% of AARs that had limited work/studies or participation in leisure activities. Most of the respondents reported some degree of anxiety related to AARs and 43% had feared for their lives. Moreover, difficulties swallowing allergy medicine at an AAR was experienced by 26% and not having the medicine available when needed by 66%. Participants with prescription of epinephrine experienced more severe AARs than those without such prescription (mean [SD] severity 6.8 [2.1] vs 5.8 [1.8], p < 0.0001); however, also those without epinephrine prescription reported considerable anxiety and impact on daily life and to a similar degree as those with prescription. ConclusionsIn this sample, subjects with experience of AARs treated with CS showed a considerable disease burden with anxiety and interruption on daily life, as well as problems related to access to, and swallowing of, medication. Although respondents with epinephrine prescription had more severe disease, a high disease burden was also evident among those without epinephrine. The study increases the knowledge of people with moderate to severe AARs, a patient population that has previously been underrepresented in the research literature.

Is chronic urticaria or urticarial vasculitis a diagnostic dilemma?

Introduction. Urticarial vasculitis (UV) is a rare disease that has two components: clinical manifestations of urticaria and histopathological signs of cutaneous leukocytoclastic vasculitis of small vessels, predominantly involving postcapillary venules. This condition is characterized by chronic or recurrent episodes of urticaria, each element of which lasts more than 24 hours and is accompanied by a feeling of pain and burning. The aim is to reveal the key points of pathogenetic mechanisms, differential diagnosis and therapeutic tactics of UV based on a clinical case. Clinical case. A clinical case of a 17-year-old boy with normocomplementemic UV is described. The patient's main complaint was a long-lasting rash (more than three weeks) with itching. From the anamnesis it is known that the provoking factors for the onset of the disease were an insect bite and the start of taking a new drug, namely vitamin K (two days before the onset of the disease). Throughout this time, the child was examined by various specialists and received treatment. Alternative diagnoses: bacterial folliculitis, viral exanthem, unspecified urticaria. There was no positive effect from the received treatment. The diagnosis of UV was made in the sixth week of the disease using a punch biopsy. Regression of the skin syndrome was achieved using a combination of antihistamine and antileukotriene drugs. Conclusions. Performing a punch biopsy, which is currently the gold standard for diagnosis, allows us to solve the diagnostic dilemma: “UV or chronic urticaria”. Timely diagnosis helps to avoid false diagnoses and, as a result, incorrect treatment of UV. The description of this clinical case is a contribution to the disclosure of this globally complex problem. The research was carried out in accordance with the principles of the Declaration of Helsinki. The informed consent of the child and child's parents was obtained for conducting the research. No conflict of interest was declared by the authors.

Carbon dots-adorned silver nanoparticles as a straightforward sustainable colorimetric sensor for the rapid detection of ketotifen in eye drops and aqueous humor

The rapid and accurate detection of drug molecules in pharmaceutical formulations and biological samples is of paramount importance. In this research article, we present a novel colorimetric sensor based on carbon dots decorated silver nanoparticles (CDs/AgNPs) for the rapid detection of ketotifen (KTF), a widely used antihistamine drug. The CDs were synthesized via a facile one-step microwave-assisted method and subsequently conjugated onto AgNPs through a simple adsorption process, forming a stable CDs/AgNPs composite. The resulting composite exhibited unique optical properties, including a strong absorption peak at 410 nm with remarkable intensity reduction and color changes upon the addition of KTF. The developed colorimetric sensor exhibited a wide linear range of 3.0–40.0 µg mL−1 (R2 = 0.9996), with a %RSD of 2.41, and a low limit of detection (LOD) of 0.981 µg mL−1. Furthermore, the sensor's practical applicability was evaluated by successfully detecting KTF in eye drops and artificial aqueous humor, demonstrating a remarkable percentage recovery exceeding 96.0 %. Finally, a comprehensive evaluation of the greenness and blueness of the method was performed using analytical eco-scale, GAPI, AGREEprep, and BAGI tools. The results of these assessments indicate its exceptional sustainability. Overall, the proposed method holds significant potential for applications in pharmaceutical quality control and therapeutic monitoring, contributing to improved patient care and drug safety in the field of ophthalmology.

Resin-Immobilized Palladium Acetate and Alcohol Dehydrogenase for Chemoenzymatic Enantioselective Synthesis of Chiral Diarylmethanols.

The enantioselective synthesis of chiral diarylmethanols is highly desirable in synthetic chemistry and the pharmaceutical industry, but it remains challenging, especially in terms of green and sustainable production. Herein, a resin-immobilized palladium acetate catalyst was fabricated with high activity, stability, and reusability in Suzuki cross-coupling reaction of acyl halides with boronic acids, and the coimmobilization of alcohol dehydrogenase and glucose dehydrogenase on resin supports was also conducted for asymmetric bioreduction of diaryl ketones. Experimental results revealed that the physicochemical properties of the resins and the immobilization modes played important roles in affecting their catalytic performances. These two catalysts enabled the construction of a chemoenzymatic cascade for the enantioselective synthesis of a series of chiral diarylmethanols in high yields (83-90%) and enantioselectivities (87-98% ee). In addition, the asymmetric synthesis of the antihistaminic and anticholinergic drugs (S)-neobenodine and (S)-carbinoxamine was also achieved from the chiral diarylmethanol precursors, demonstrating the synthetic utility of the chemoenzymatic cascade.

Assessment of pheniramine in alternative biological matrices by liquid chromatography tandem mass spectrometry.

Pheniramine is an over-the-counter antihistamine drug. Its accessibility and low cost made it more popular among drug abusers in Pakistan. In this study, pheniramine was quantified in both conventional and alternative specimens of twenty chronic drug abusers, aged 16-50years, who were positive for pheniramine in comprehensive toxicological screening for drugs by gas chromatography with mass spectral detection in positive electron impact mode. Pheniramine was extracted from biological specimens using solid phase extraction and liquid chromatography tandem mass spectrometry was employed for quantification. Chromatographic separation was carried out on a Poroshell120EC-18 (2.1mm × 50mm × 2.7µm) column using water-acetonitrile in formic acid (0.1%) mobile phase in gradient elution mode with 500μL/min flow rate. Positive electrospray ionization mode and multi-reaction monitoring with ion transitionsm/z241.3 → 195.8 and 167.1 for pheniramine andm/zm/z247.6 → 173.1 for pheniramine-d6 were employed. The quantification method showed good linear ranges of 2-1000ng/mL in blood, urine, and oral fluid; 2-1000ng/mg in hair and 5-1000ng/mg in nail with ≥ 0.985% coefficient of linearity. The retention time of pheniramine was 3.0 ± 0.1min. The detection and lower quantification limits were 1ng/mL and 2ng/mL for blood, urine, oral fluid and hair whereas 2.5ng/mg and 5ng/mg for nail, respectively. Mean extraction recovery and ionization suppression ranged 86.3-95.1% and -4.6 to -14.4% in the studied matrices. Intra-day and inter-day precision were 4.1-9.3% and 2.8-11.2%, respectively. Pheniramine levels in specimens of drug abusers were 23-480ng/mL in blood, 72-735ng/mL in urine, 25-379ng/mL in oral fluid, 10-170ng/mg in hair and 8-86ng/mg in nail specimens. Alternative specimens are of utmost significance in clinical and medico-legal cases. In this study, authors compared matrix-matched calibration curves to blood calibration curve and obtained results within ± 10%; thereby justifying the use of blood calibration curve for urine, oral fluid, hair, and nail specimens.