Search Results (189)

People with cystic fibrosis may experience polypharmacy, which can increase the risk of drug induced complications such as adverse events and drug–drug interactions. This study aimed to examine the prevalence of adverse events and to identify potential drug–drug interactions associated with elexacaftor/tezacaftor/ivacaftor (ETI). Three databases, the Australian Therapeutic Goods Administration Database of Adverse Event Notification (TGA DAEN), the Canada Vigilance Adverse Reaction Online Database (CVAROD), and the USA Food and Drug Administration Adverse Event Reporting System (FAERS) Database were searched for spontaneous ETI adverse events between 2019 and 2024. Descriptive analysis of the data was undertaken. The FAERS database was analysed to identify adverse events of interest such as anxiety and depression and concomitant drugs prescribed with ETI. A total of 10,628 ETI associated adverse events were identified in all system organ classes. The incidence of psychiatric adverse events ranged from 7 to 15% across the three databases. Potential drug–drug interactions with CYP 3A4/5 strong inhibitors and strong inducers were identified from the FAERS database and azole antifungals were implicated in several ETI dose modifications. The prevalence and types of ETI adverse events were varied and use of concomitant drugs with potential drug interactions was significant, requiring more research to manage them. Full article

IgG antibodies, particularly those of the IgG4 subclass, have generated significant debate regarding their role in immune tolerance versus food intolerance. This article comprehensively reviews the literature on the subject, exploring evidence from healthy individuals and patient populations with varied clinical conditions. On one hand, IgG—especially IgG4—is frequently detected in individuals without adverse food reactions and may represent a normal adaptive immune response to constant dietary antigen exposure, contributing to the development of regulatory T-cell–mediated tolerance. On the other hand, several studies have linked elevated food-specific IgG levels with conditions characterized by increased intestinal permeability and inflammation, including eosinophilic esophagitis, irritable bowel syndrome, inflammatory bowel disease, and autoimmune disorders. The review discusses multiple investigations where IgG-guided elimination diets have yielded symptomatic improvements, suggesting a potential benefit for targeted dietary interventions. However, these findings are tempered by the observation that IgG antibodies are commonly present in asymptomatic individuals, thereby questioning their specificity as markers of adverse food reactions. Current diagnostic guidelines from leading allergy and immunology organizations discourage routine IgG testing for food allergies and intolerances, highlighting that these antibodies might instead indicate exposure or underlying inflammation rather than an actual pathogenic mechanism. There is a need for well-controlled, large-scale studies to clearly define the clinical relevance of food-specific IgG responses. Until more substantial evidence is provided, clinicians are advised to interpret the IgG results cautiously and to consider them within the broader context of each patient’s clinical presentation before recommending restrictive dietary changes. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause hypersensitivity reactions and lead to anaphylactic shock. These drugs also act as cofactors in allergic reactions. Lipid transfer proteins (LTPs), found in plants, represent a unique group of allergens in which cofactors play a crucial role. This case report describes a 26-year-old female who developed anaphylactic symptoms after ingesting grapes and taking ketoprofen. The patient experienced swelling of the lips, tongue, and throat, as well as shortness of breath, dizziness, and loss of consciousness, after consuming grapes and taking ketoprofen. She had previously used ketoprofen and acetylsalicylic acid without issues but had developed urticaria on several occasions after consuming multi-ingredient dishes. Skin prick tests showed positive results for peanut and orange allergens. Further testing using the ALEX multiparametric test detected antibodies to several LTP allergens. Intradermal tests with ketoprofen yielded a positive result, although irritant reactions could not be ruled out. A provocation test with acetylsalicylic acid (ASA) showed no adverse reactions. Skin tests with ibuprofen were negative, and provocation tests confirmed its tolerance. A diagnosis of LTP allergy and selective ketoprofen allergy was made, with the recommendation to avoid ketoprofen and follow a diet excluding foods from the LTP group. Full article

Background and objectives: As part of Vision 2030, Saudi Arabia aims to strengthen its healthcare system by enhancing efficiency, reducing medical errors, and ensuring drug safety. Evidence on pharmacists’ experiences with adverse drug reactions (ADRs) in daily practice remains limited. Gaining insight into their perspectives is essential for improving patient safety and optimizing pharmaceutical care. Therefore, we aimed to assess pharmacists’ ability to identify ADRs in daily practice and the subsequent actions taken upon identification. Methods: Between July and August 2024, an email-based invitation was sent to randomly selected registered community and hospital pharmacists in Saudi Arabia to participate in the study, which employed a piloted questionnaire. Results: The study involved 305 pharmacists, including 169 hospital/clinical pharmacists (HCPs, 55.4%) and 136 community pharmacists (CPs, 44.6%). A majority (n = 251, 82.3%) indicated direct patient encounters, while 67.2% (n = 205) reported observing suspected ADRs in the preceding 12 months. Most respondents filed ADR reports to the Saudi Food and Drug Administration/National Pharmacovigilance Centre (HCP = 103, CP = 60) and hospital drug information centers (HCP = 89, CP = 64), with online forms being the favored mode (HCP = 122, CP = 96). Awareness of ADR reporting procedures was reported by 128 HCPs and 80 CPs. Conclusions: More than two-thirds of participants reported having participated in ADR reporting, with greater adherence observed in hospital settings. Pharmacists predominantly depend on the Saudi Food and Drug Administration/National Pharmacovigilance Centre and hospital drug information centers for reporting, with a preference for online submission methods. Targeted educational interventions addressing gaps in knowledge, reporting procedures, and form complexity could improve ADR reporting practices. These findings support the need for structured training and policy measures to strengthen pharmacovigilance system. Full article

The mRNA vaccine has protected humans from the Coronavirus disease 2019 (COVID-19) and has taken the lead in reversing the epidemic efficiently. However, the Centre of Disease Control (CDC) reported and raised the alarm of allergic or acute inflammatory adverse reactions after vaccination with mRNA-LNP vaccines. Meanwhile, the US Food and Drug Administration (FDA) has added four black-box warnings in the instructions for mRNA-LNP vaccines. Numerous studies have proven that the observance of side effects after vaccination is indeed positively correlated to the level of anti-PEG antibodies (IgM or IgG), which are enhanced by PEGylated preparations like LNP vaccine and environmental exposure. After literature research and review in the past two decades, it was found that the many clinical trial failures (BIND-014, RB006 fell in phase II) of PEG modified delivery system or PEGylated drug were related to the high expression of anti-PEG IgM and IgG. In the background of shooting multiple mRNA-LNP vaccines in billions of people around the world in the past three years, the level of anti-PEG antibodies in the population may have significantly increased, which brings potential risks for PEG-modified drug development and clinical safety. This review summarizes the experience of using mRNA-LNP vaccines from the mechanism of the anti-PEG antibodies generation, detection methods, clinical failure cases of PEG-containing products, harm analysis of abuse of PEGylation, and alternatives. In light of the increasing prevalence of anti-PEG antibodies in the population and the need to avoid secondary injuries, this review article holds greater significance by offering insights for drug developers. It suggests avoiding the use of PEG excipients when designing PEGylated drugs or PEG-modified nano-formulations and provides references for strategies such as utilizing PEG-free or alternative excipients. Full article

Background/Objectives: Inflammatory disorders contribute to the pathogenesis of numerous diseases and are known to markedly reduce quality of life. Although anti-inflammatory drugs approved by the Food and Drug Administration are available, their prolonged use is frequently associated with adverse effects. In this study, we evaluated the pharmacological properties of araliadiol, a naturally occurring polyacetylene compound, as a novel anti-inflammatory agent. Methods: An in vitro hyperinflammatory model was established by stimulating RAW 264.7 cells with lipopolysaccharide (LPS). Dexamethasone (DEX) was used as a positive control to compare anti-inflammatory efficacy. The protective effects of araliadiol against LPS-induced cytotoxicity were assessed using adenosine triphosphate content and crystal violet staining assays. The anti-inflammatory activity was further examined by quantitative reverse transcriptase–polymerase chain reaction, Western blotting, cell fractionation, immunofluorescence staining, a nitric oxide assay, and an enzyme-linked immunosorbent assay. Results: Araliadiol significantly attenuated cytotoxicity and cell death in LPS-stimulated RAW 264.7 cells. It suppressed the expression of cell death markers Cleaved caspase-3 and Cleaved PARP-1. In addition, araliadiol downregulated key pro-inflammatory mediators, including inflammasome-related genes, cytokines, chemokines, and inducible nitric oxide synthase. It also reduced the expression of Cox-2 and PGE₂, indicating potential anti-hyperalgesic effects. Moreover, araliadiol inhibited the activation of Nfκb and Stat1 signaling pathways in LPS-stimulated macrophages. Conclusions: Araliadiol demonstrated robust anti-cytotoxic, anti-inflammatory, and anti-hyperalgesic activities in LPS-induced RAW 264.7 cells, with efficacy comparable to DEX. These findings support its potential as a plant-derived therapeutic candidate for the management of inflammatory conditions. Full article

Acrylamide, a harmful substance generated during the normal thermal treatment of foods, has been shown to adversely affect human health, particularly the vital intestinal barrier function. Meanwhile, natural polysaccharides are recognized to exert an important biofunction in the intestine by protecting barrier integrity. In this study, the non-starch, water-soluble, and nondigestive yam polysaccharide (YP) was extracted from fresh Chinese yam, while two selenylated derivatives with different extents of selenylation were prepared via the HNO₃-Na₂SeO₃ reaction system, and designated as YPSe-I and YPSe-II, respectively. Their protective activities and the associated molecular mechanisms of these substances against acrylamide-induced damage in rat intestinal epithelial (IEC-6) cells were thereby investigated. The experimental results demonstrated that the selenium contents of YPSe-I and YPSe-II were 0.80 and 1.48 g/kg, respectively, whereas that of the original YP was merely 0.04 g/kg. In IEC-6 cells, in comparison with YP, both YPSe-I and YPSe-II showed higher efficacy than YP in alleviating acrylamide-induced cell toxicity through promoting cell viability, suppressing the release of lactate dehydrogenase, and decreasing the generation of intracellular reactive oxygen species. Both YPSe-I and YPSe-II could also manifest higher effectiveness than YP in maintaining cell barrier integrity against the acrylamide-induced barrier disruption. The mentioned barrier protection was achieved by increasing transepithelial electrical resistance, reducing paracellular permeability, facilitating the distribution and expression of F-actin between the cells, and up-regulating the production of three tight junctions, namely ZO-1, occludin, and claudin-1. Additionally, acrylamide was observed to trigger the activation of the MAPK signaling pathway, thereby leading to cell barrier dysfunction. In contrast, YPSe-I and particularly YPSe-II were capable of down-regulating two MAPK-related proteins, namely p-p38 and p-JNK, and thereby inhibiting the acrylamide-induced activation of the MAPK signaling pathway. Moreover, YPSe-II in the cells was consistently shown to provide greater barrier protection than YPSe-I. In conclusion, chemical selenylation of YP could cause higher activity in mitigating acrylamide-induced cytotoxicity and intestinal barrier dysfunction, while the efficacy of activity enhancement was positively affected by the selenylation extent. Full article

Food allergies are becoming more common globally. The strict elimination diet, as the main approach so far, has a negative impact on different areas of the lives of children suffering from food allergies, as well as on their caregivers. Oral immunotherapy (OIT), which consists of ingesting small, gradually increasing amounts of food allergens, is a promising approach. Although efficient, this approach is accompanied by frequent adverse reactions (AR), some of which are as severe as anaphylaxis. It seems that, generally, slow dose escalation, as well as low maintenance doses with longer durations, make OIT safer, especially in children with severe food allergies. Furthermore, less allergenic forms of allergens, such as baked milk or egg, also contribute to OIT safety. Adjuvant therapy in combination with OIT has the potential to improve OIT efficiency and safety. Treatment with monoclonal antibodies such as omalizumab and dupilumab in combination with OIT is promising. While both could improve efficiency, omalizumab seems to have a better effect on safety. Interferon γ shows promising results. In contrast, the effect of probiotics and vitamin D supplementation in combination with OIT is still controversial, and new trials about their synergistic effect are needed. Full article

Background: Food allergy (FA) poses a major global health issue due to the increasing prevalence and lack of effective prevention strategies. Allergen-specific immunotherapy (AIT) has emerged as a disease-modifying therapy for FA. However, due to long-term treatment duration and unexpected adverse reactions, only a minority of patients benefit from AIT. Therefore, effective prophylactic interventions are urgently needed for FA patients. Methods: In this proof-of-concept study, using a well-established mRNA platform, we developed mRNA vaccine candidates encoding for the major egg white allergen Gal d2 and comprehensively evaluated their prophylactic efficacy against anaphylaxis in a Gal d2-induced allergic mouse model. Results: Two vaccine formulations, Gal d2 mRNA vaccine and Gal d2-IL-10 mRNA vaccine, both demonstrated potent ability in inducing allergen-specific IgG and Th1-type T cells. Importantly, the two vaccine formulations showed promise in preventing the onset of allergic disease, which is indicated by prevention of body temperature decline during anaphylaxis. Conclusions: We provided preliminary proof-of-concept evidence showing that the mRNA platform is unique and holds promise for the development of anti-allergy vaccines. This is largely attributed to the capacities of mRNA vaccines in eliciting an allergen-blocking antibody, shifting Th2 towards Th1 immunity, as well as in generating peripheral tolerance. However, further investigations are required to better understand the mode of action. Full article

Omalizumab (OMA) is gaining recognition as a promising therapeutic approach for IgE-mediated food allergies in pediatric patients. We conducted a review analyzing 22 studies, including randomized controlled trials, observational studies, and case reports, to evaluate the efficacy and safety of OMA in food allergy management in children and adolescents. The results indicate that OMA, whether used as monotherapy or in combination with oral immunotherapy (OIT), significantly increases allergen tolerance, reduces the severity of allergic reactions, and improves patients’ quality of life. When used alongside OIT, OMA reduced adverse reactions during dose escalation and maintenance phases, facilitating safer and more effective desensitization. Additionally, OMA demonstrated benefits beyond food allergy management, including improved asthma control and a reduction in food allergy-related anxiety. However, challenges remain, including high costs, the need for standardized treatment protocols, and limitations related to total IgE thresholds for eligibility. While OMA has been FDA-approved for food allergy treatment in the United States, further research is needed to establish long-term efficacy, optimal dosing strategies, and its role in sustained tolerance development. Future research should focus on optimizing treatment protocols and identifying which patients will benefit the most. Integrating omalizumab into food allergy management could revolutionize pediatric care, offering hope for a safer, more effective approach to desensitization. Full article

(1): Background: This study aimed to evaluate the concentrations of four proteins for allergic patch testing (APT) in dogs, assessing sensitivity (SE), specificity (SP), negative predictive value (NPV), positive predictive value (PPV), reactions to adhesives/containers, and the safety of APT with food proteins in dogs. (2) Methods: For evaluation, 43 dogs were screened and divided into two groups: Group 1 consisted of 20 healthy dogs, and Group 2 included 23 dogs with canine atopic dermatitis (AD). Group 1 underwent allergic patch testing (APT) with beef, pork, chicken, and soy proteins at four different concentrations (100 mg, 250 mg, 500 mg, 1000 mg/0.2 mL). Of the 23 dogs included in Group 2, four did not undergo the elimination diet and were excluded, leaving 17 dogs in the study. They underwent an elimination diet (ED) and were evaluated using the pruritus visual analog scale (pVAS) and lesion scores (CADESI-4) before and after the ED (days 0 and 45). After the ED, Group 2 was subjected to APT (using the same proteins and concentrations as Group 1) and an oral provocation test (OPT) with the proteins used in the APT. The results of the OPT were used to assess the accuracy of the APT. (3) Results: In Group 1, one dog reacted to the APT. In Group 2, after 45 days of ED, of the 17 dogs included, 13 showed a reduction in pVAS and CADESI-4 scores (p < 0.05) and nine an improvement considered good to excellent. Of these, two showed irritant contact reactions to the APT chambers and were excluded, leaving 11 dogs that were reactive to APT, and the OPT increased pruritus (p < 0.05). Accuracy: Beef and chicken proteins at concentrations of 500 and 1000 mg/0.2 mL, and soy protein at 1000 mg/0.2 mL, achieved 100% SE, SP, PPV, and NPV. Pork protein at 1000 mg/0.2 mL achieved 100% SE, 83% SP, 83% PPV, and 100% NPV. (4) Conclusions: APT with beef and chicken proteins at 500 mg and 1000 mg/0.2 mL and soy protein at 1000 mg/0.2 mL, based on the results of this study, can be recommended for diagnosing adverse food reactions in dogs with AD. Full article

Background/Objectives: Food hypersensitivity remains an understudied and overlooked subject globally. It is characterized by adverse reactions to dietary substances, potentially triggered by various mechanisms. Food allergy, a subset of food hypersensitivity, denotes an immune response to food proteins categorized into immunoglobulin IgE-mediated or non-IgE-mediated reactions. Conversely, food intolerance, another facet of food hypersensitivity, refers to non-immunological reactions, in which the human body cannot properly digest certain foods or components, leading to gastrointestinal discomfort and other non-immune-related symptoms. The main objective of this study was to determine and differentiate the differences, characteristics, and types of food hypersensitivity. Methods: This study involved a comprehensive review of key research from 1990 onward, including review articles, prospective studies, nested case–control studies, and meta-analyses. Results: Recognizing these differences is essential for healthcare professionals to ensure accurate diagnosis, effective management, and improved patient outcomes, while also aiding dietitians in providing optimal nutritional and dietary guidance. Conclusions: there are big differences between the main characteristics, such as symptoms, complications, and treatments between allergies, and food intolerances. Commonly reported trigger foods include cow milk, gluten, eggs, nuts, and seafood. Full article

Dietary supplements are commonly employed to provide additional nutritional support for athletes. In taekwondo, there is a need for evidence-based analyses to evaluate the effects of dietary supplements on training outcomes, competitive performance, and injury recovery. Taekwondo primarily relies on oxidative metabolism, yet decisive lower-limb attacks depend on non-oxidative pathways. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science databases in November 2024, utilizing keywords including ‘Dietary Supplements’, ‘Supplements’, ‘Food Supplementations’, and ‘Taekwondo’. Of the 203 articles identified, 26 met the inclusion criteria, collectively assessing the impact of 14 different dietary supplements. Among these studies, eight provided strong evidence that acute ingestion of 3–5 mg/kg of caffeine significantly enhanced athletes’ physical performance and psychological well-being. However, the ergogenic effects of the compound Fufang Ejiaojiang, creatine, sodium bicarbonate, beetroot, vitamins, and long beans require further investigation to validate their efficacy. Additionally, dietary supplements, such as amino acids, turmeric powder, ginger, spirulina, octacosanol, nucleotides, and yogurt, can reduce fatigue, supporting injury recovery, and boosting immune function, although current evidence remains insufficient. Future research should pay closer attention to reporting adverse reactions linked to dietary supplements. Doing so would provide coaches and athletes with more reliable safety information, supporting safer choices and reducing potential health risks. Full article

Background/Objectives: Drug-induced Guillain–Barré Syndrome (GBS) is a severe complication of pharmacotherapy. Previous research has established a connection between certain medications and higher GBS risk. However, a large-cohort analysis is crucial to reveal underlying biological mechanisms of drug-induced GBS. This study aimed to evaluate the association between GBS and various drugs currently accessible in the Food and Drug Administration Adverse Event Reporting System (FAERS) database and explore the mechanisms underlying drug-induced GBS. Methods: We analyzed drug-induced GBS adverse event reports in the FAERS database to identify strongly associated drugs. We then investigated GBS susceptibility proteins through GWAS meta-analysis and Mendelian Randomization (MR) based on plasma proteomics, complemented by protein–protein interaction (PPI) network analysis to explore underlying mechanisms. Results: A total of 4094 FAERS reports were analyzed, leading to the selection of 30 drugs with the highest signal strength and 54 drug targets. MR analysis identified 73 susceptibility proteins linked to GBS risk. PPI analysis revealed that 10 genes encoding GBS-susceptible proteins were associated with 19 drug target genes involved in 13 different drugs. Among these, the antineoplastic drug Nelarabine showed the strongest correlation with GBS. The TNF and PDCD1LG2 genes emerged as key GBS-susceptible genes. Additionally, TNF was negatively correlated with GBS, and PDCD1LG2 was positively correlated with GBS. KEGG analysis indicated that pyrimidine metabolism, purine metabolism, and the IL6/JAK/STAT3 signaling pathway also significantly contribute to drug-induced GBS. Conclusions: This study improved our understanding of the biological mechanisms of drug-induced GBS, thereby pinpointing potential therapeutic targets for future intervention. Full article

Vitamin B12 is the common name for a group of cobalamins, which are cobalt corrines. Cobalamins are water-soluble B vitamins. Vitamin B12, as a coenzyme of various enzymes, is an essential component of many key metabolic processes in the body. Vitamin B12 deficiency causes dysfunction of various organs and systems in the body, including the central nervous system. Humans, like other animals, are unable to synthesize cobalamin. This vitamin must be supplied with a balanced diet. The only valuable dietary sources of cobalamin are foods of animal origin, especially offal (e.g., liver). Vegan and vegetarian diets are deficient in vitamin B12. People who follow this nutritional model require systematic cobalamin supplementation, usually in oral form. Other causes of cobalamin deficiency are various pathogenetic processes, in the course of which any of the stages of the complicated process of absorption of this vitamin from the gastrointestinal tract are impaired. Disorders of intestinal absorption of vitamin B12 require systematic supplementation of cobalamin parenterally (usually by intramuscular or subcutaneous injections) for the rest of life. Supplementary therapy with vitamin B12 may cause various adverse reactions, among which hypersensitivity reactions of various spectrums and intensity of symptoms are possible. According to available data, hypersensitivity to cobalamin is more likely after intramuscular or subcutaneous administration than in oral form. It also seems that long-term administration of cobalamin predisposes to allergy to vitamin B12, regardless of its chemical form. Although hypersensitivity to cobalamin is rather rare, it can also be of great clinical importance. This is due to the fact that vitamin B12 deficiency affects a significant part of the population, especially the elderly and those with chronic diseases that impair its absorption. In addition, supplementary therapy with cobalamin is long-term (usually lifelong) and there is no alternative form of treatment. For these reasons, solutions are sought that will allow for the safe continuation of treatment supplementing cobalamin deficiency. Various cyanocobalamin desensitization protocols are proposed, differing in duration, the dynamics of gradual dose increase, or the method of injection (intramuscular or subcutaneous). An analysis of available data in this field suggests that desensitization with cyanocobalamin seems to be an effective way to obtain tolerance to vitamin B12, allowing for long-term supplementation of this vitamin regardless of the chemical form, dose size, frequency, or route of administration. Full article