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Cureus Jan 2024Galactose-⍺-1, 3-galactose (alpha-gal) is an oligosaccharide found in mammalian tissues that causes allergic reactions in patients with alpha-gal syndrome (AGS). AGS... (Review)
Review
Galactose-⍺-1, 3-galactose (alpha-gal) is an oligosaccharide found in mammalian tissues that causes allergic reactions in patients with alpha-gal syndrome (AGS). AGS is a hypersensitivity reaction notable for both immediate and delayed allergic and anaphylactic symptoms. As a tick-based disease, AGS has gained increasing prevalence across the United States and can have a significant influence on which medications are safe for patients. Many medications used within the operating room and intensive care units have inactive ingredients that can be mammalian-derived and therefore should be vetted before administering to patients with AGS. Management of patients with AGS involves diligent action in the preoperative and perioperative settings to reduce patient exposure to potentially harmful medications. In conducting a comprehensive risk stratification assessment, the anesthesia team should identify any at-risk patients and determine which medications they have safely tolerated in the past. Despite obtaining a complete history, not all patients with AGS will be identified preoperatively. The perioperative team should understand which common medications pose a risk of containing alpha-gal moieties (e.g., heparins, gelatin capsules, vaccines, lidocaine patches, surgifoam, etc.). For this reason, this paper includes a compendium of common anesthetic medications that have been cross-referenced for ingredients that have the potential to cause an AGS reaction. Any potentially unsafe medications have been identified such that medical providers can cross-reference with the ingredients listed at their respective institutions.
PubMed: 38425598
DOI: 10.7759/cureus.53208 -
Environment International Sep 2023Prenatal exposure to mixtures of endocrine disrupting chemicals (EDC) has the potential to disrupt human metabolism. Prenatal periods are especially sensitive as many...
BACKGROUND
Prenatal exposure to mixtures of endocrine disrupting chemicals (EDC) has the potential to disrupt human metabolism. Prenatal periods are especially sensitive as many developmental processes are regulated by hormones. Prenatal exposure to EDCs has inconsistently been associated with children's body mass index (BMI) and obesity. The objective of this study was to investigate if prenatal exposure to a mixture of EDCs was associated with children's BMI and overweight (ISO-BMI ≥ 25) at 5.5 years of age, and if there were sex-specific effects.
METHODS
A total of 1,105 mother-child pairs with complete data on prenatal EDCs concentrations (e.g., phthalates, non-phthalate plasticizers, phenols, PAH, pesticides, PFAS, organochlorine pesticides, and PCBs), children's measured height and weight, and selected covariates in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study were included in this analysis. The mixture effect of EDCs with children's BMI and overweight was assessed using WQS regression with 100 repeated holdouts. A positively associated WQS index with higher BMI and odds of overweight was derived. Models with interaction term and stratified weights by sex was applied in order to evaluate sex-specific associations.
RESULTS
A significant WQS*sex interaction term was identified and associations for boys and girls were in opposite directions. Higher prenatal exposure to a mixture of EDCs was associated with lower BMI (Mean β = -0.19, 95%CI: -0.40, 0.01) and lower odds of overweight (Mean OR = 0.72, 95%CI: 0.48, 1.04) among girls with borderline significance. However, the association among boys did not reach statistical significance. Among girls, the possible chemicals of concern were MEP, 2-OHPH, BPF, BPS, DPP and PFNA.
CONCLUSION
Prenatal exposure to a mixture of EDCs was associated with lower BMI and overweight among girls, and non-significant associations among boys. Chemicals of concern for girls included phthalates, non-phthalate plasticizers, bisphenols, PAHs, and PFAS.
Topics: Male; Female; Pregnancy; Humans; Body Mass Index; Endocrine Disruptors; Overweight; Plasticizers; Prenatal Exposure Delayed Effects; Sweden; Hypersensitivity; Asthma; Environmental Illness; Fluorocarbons
PubMed: 37672941
DOI: 10.1016/j.envint.2023.108176 -
Jornal de Pediatria 2024Evaluate biomarkers capable of safely guiding Yellow fever vaccine (YFV) vaccination among individuals suspicious of hen's egg allergy, and identify factors associated...
OBJECTIVE
Evaluate biomarkers capable of safely guiding Yellow fever vaccine (YFV) vaccination among individuals suspicious of hen's egg allergy, and identify factors associated with a higher risk for adverse events after immunization (AEAI).
METHODS
Patients underwent skin prick test (SPT) for standardized allergens: whole egg, egg white, egg yolk; YFV (1:10 dilution; Biomanguinhos-Fiocruz), and intradermal test (IDT; YFV 0.02 mL, 1:100 dilution) and positive and negative controls. Serum levels of specific IgE (sIgE) for a whole egg, egg white, egg yolk, egg albumin, ovomucoid, lysozyme, and conalbumin (ImmunoCap®; ThermoFisher®) were obtained. Patients sensitized to YFV were submitted to YFV desensitization, and those negatives received YFV (0.5mL) and remained under surveillance for at least one hour.
RESULTS
103 patients were enrolled, 95% under 12 years old. 71% (81/103) of patients had reactions: 80% immediate, 11% mixed, and 9% delayed. There was an association between positive skin test results with YFV and the severity of the reaction (OR:7.64; 95%CI:1.61-36.32; p = 0,011). Only the presence of sIgE to ovomucoid was associated with clinical symptoms (p = 0,025). Thirty patients underwent the YFV desensitization protocol.
CONCLUSION
There is a relationship between the positivity of the egg's components and the severity of the clinical reaction. Furthermore, the relationship between the positivity of the tests with the YFV and egg's components may show a tendency to look at ovomucoid and conalbumin, but it is not a certainty. Therefore, further studies are needed to confirm these associations, and for now, the authors still recommend using the vaccine for testing when necessary.
Topics: Humans; Animals; Female; Child; Egg Hypersensitivity; Ovomucin; Yellow Fever; Conalbumin; Chickens; Immunoglobulin E; Vaccination; Allergens
PubMed: 37597532
DOI: 10.1016/j.jped.2023.07.004 -
Journal of Advanced Research May 2024Rice flowering is a major agronomic trait, determining yield and ecological adaptability in particular regions. ABA plays an essential role in rice flowering, but the...
INTRODUCTION
Rice flowering is a major agronomic trait, determining yield and ecological adaptability in particular regions. ABA plays an essential role in rice flowering, but the underlying molecular mechanism remains largely elusive.
OBJECTIVES
In this study, we demonstrated a "SAPK8-ABF1-Ehd1/Ehd2" pathway, through which exogenous ABA represses rice flowering in a photoperiod-independent manner.
METHODS
We generated abf1 and sapk8 mutants using the CRISPR-Cas9 method. Using yeast two-hybrid, Pull down, BiFC and kinase assays, SAPK8 interacted and phosphorylated ABF1. ABF1 directly bound to the promoters of Ehd1 and Ehd2 using ChIP-qPCR, EMSA, and LUC transient transcriptional activity assay, and suppressed the transcription of these genes.
RESULTS
Under both long day and short day conditions, simultaneous knock-out of ABF1 and its homolog bZIP40 accelerated flowering, while SAPK8 and ABF1 over-expression lines exhibited delayed flowering and hypersensitivity to ABA-mediated flowering repression. After perceiving the ABA signal, SAPK8 physically binds to and phosphorylates ABF1 to enhance its binding to the promoters of master positive flowering regulators Ehd1 and Ehd2. Upon interacting with FIE2, ABF1 recruited PRC2 complex to deposit H3K27me3 suppressive histone modification on Ehd1 and Ehd2 to suppress these genes transcription, thereby leading to later flowering.
CONCLUSION
Our work highlighted the biological functions of SAPK8 and ABF1 in ABA signaling, flowering control and the involvement of a PRC2-mediated epigenetic repression mechanism in the transcription regulation governed by ABF1 on ABA-mediated rice flowering repression.
Topics: Abscisic Acid; Oryza; Flowers; Gene Expression Regulation, Plant; Plant Proteins; Signal Transduction; Plants, Genetically Modified; Phosphorylation; Promoter Regions, Genetic; Photoperiod; Transcription Factors
PubMed: 37399924
DOI: 10.1016/j.jare.2023.06.012 -
Immunity Feb 2024Antibodies can block immune receptor engagement or trigger the receptor machinery to initiate signaling. We hypothesized that antibody agonists trigger signaling by...
Antibodies can block immune receptor engagement or trigger the receptor machinery to initiate signaling. We hypothesized that antibody agonists trigger signaling by sterically excluding large receptor-type protein tyrosine phosphatases (RPTPs) such as CD45 from sites of receptor engagement. An agonist targeting the costimulatory receptor CD28 produced signals that depended on antibody immobilization and were sensitive to the sizes of the receptor, the RPTPs, and the antibody itself. Although both the agonist and a non-agonistic anti-CD28 antibody locally excluded CD45, the agonistic antibody was more effective. An anti-PD-1 antibody that bound membrane proximally excluded CD45, triggered Src homology 2 domain-containing phosphatase 2 recruitment, and suppressed systemic lupus erythematosus and delayed-type hypersensitivity in experimental models. Paradoxically, nivolumab and pembrolizumab, anti-PD-1-blocking antibodies used clinically, also excluded CD45 and were agonistic in certain settings. Reducing these agonistic effects using antibody engineering improved PD-1 blockade. These findings establish a framework for developing new and improved therapies for autoimmunity and cancer.
Topics: Protein Tyrosine Phosphatases; Signal Transduction; CD28 Antigens; Receptors, Immunologic
PubMed: 38354703
DOI: 10.1016/j.immuni.2024.01.007 -
Practical Approach to Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Children.Pharmaceuticals (Basel, Switzerland) Sep 2023We aimed to assess the real-life prevalence, patient profile, and clinical presentation of drug hypersensitivity to NSAIDs in children after an incidence of an adverse...
BACKGROUND
We aimed to assess the real-life prevalence, patient profile, and clinical presentation of drug hypersensitivity to NSAIDs in children after an incidence of an adverse event during treatment, verified by a drug challenge test.
METHODS
We included 56 children, aged 4-18 years, referred to our allergy clinic due to the incidence of adverse reaction during treatment. Skin prick tests and a drug provocation test were performed in all patients. Diagnostics for persistent urticaria were performed.
RESULTS
In 56 patients suspected of drug allergy, we proved NSAID hypersensitivity in 17 patients (30.1%). In 84.9% ( = 47) of patients, the clinical manifestations of hypersensitivity revealed angioedema and urticaria. The most common culprit drug among NSAIDs in children was ibuprofen. Thirty-one (55.4%) reactions were immediate, and 25 (44.6%) were delayed or late. Previous history of allergy was a risk factor for NSAID hypersensitivity ( = 0.001). Vitamin D deficiency in the blood serum was a risk factor for NASID hypersensitivity (OR = 5.76 (95% Cl: 1.42-23.41)).
CONCLUSIONS
Hypersensitivity to NSAIDs is a difficult diagnostic problem in pediatric allergy. The most common manifestation of hypersensitivity to ibuprofen in children is acute urticaria and angioedema. Two important problems in the differential diagnosis are cofactors such as vitamin D levels and viral infections, which require further research.
PubMed: 37765044
DOI: 10.3390/ph16091237 -
Nutrients Jan 2024Due to its very early introduction, cow's milk is one of the first foods that can cause adverse reactions in human beings. Lactose intolerance (LI) and cow's milk... (Review)
Review
Due to its very early introduction, cow's milk is one of the first foods that can cause adverse reactions in human beings. Lactose intolerance (LI) and cow's milk allergy (CMA) are the most common adverse reactions to cow's milk. While LI is due to insufficient small intestinal lactase activity and/or a large quantity of ingested lactose, CMA is an aberrant immune reaction to cow's milk proteins, particularly casein or β-lactoglobulin. However, the clinical manifestations of LI and CMA, particularly their gastrointestinal signs and symptoms, are very similar, which might lead to misdiagnosis or delayed diagnosis as well as nutritional risks due to inappropriate dietary interventions or unnecessary dietary restriction. Formula-fed infants with LI should be treated with formula with reduced or no lactose, while those with CMA should be treated with formula containing extensive hydrolyzed cow's milk protein or amino acids. This review is therefore written to assist clinicians to better understand the pathophysiologies of LI and CMA as well as to recognize the similarities and differences between clinical manifestations of LI and CMA.
Topics: Infant; Animals; Cattle; Female; Humans; Milk Hypersensitivity; Lactose Intolerance; Milk; Caseins; Allergens; Protein Hydrolysates; Milk Proteins
PubMed: 38337698
DOI: 10.3390/nu16030414 -
International Journal of Molecular... Apr 2024Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative... (Review)
Review
Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to systematically characterize G-CSF-induced HRs while including a comprehensive list of adverse reactions. We reviewed articles published before January 2024 by searching in the PubMed, Embase, Cochrane Library, and Web of Science databases using a combination of the keywords listed, selected the ones needed, and extracted relevant data. The search resulted in 68 entries, 17 relevant to our study and 7 others found from manually searching bibliographic sources. A total of 40 cases of G-CSF-induced HR were described and classified as immediate (29) or delayed (11). Immediate ones were mostly caused by filgrastim (13 minimum), with at least 9 being grade 5 on the WAO anaphylaxis scale. Delayed reactions were mostly maculopapular exanthemas and allowed for the continuation of G-CSF. Reactions after first exposure frequently appeared and were present in at least 11 of the 40 cases. Only five desensitization protocols have been found concerning the topic at hand in the analyzed data. We believe this study brings to light the research interest in this topic that could benefit from further exploration, and propose regular updating to include the most recently published evidence.
Topics: Humans; Granulocyte Colony-Stimulating Factor; Drug Hypersensitivity
PubMed: 38732026
DOI: 10.3390/ijms25094807 -
Pulmonary Pharmacology & Therapeutics Dec 2023The tyrosine kinase inhibitor nintedanib has been recently approved for the treatment of Interstitial Lung Diseases (ILDs) that manifest a progressive fibrosis phenotype...
The tyrosine kinase inhibitor nintedanib has been recently approved for the treatment of Interstitial Lung Diseases (ILDs) that manifest a progressive fibrosis phenotype other than Idiopathic pulmonary Fibrosis (IPF). Nintedanib reduces the development of lung fibrosis in various animal models resembling features of PF-ILD and in vitro, it inhibits the fibrosing phenotype of human lung fibroblasts (HLFs) isolated from patients with IPF. To get insight on the cellular and molecular mechanisms that drive the clinical efficiency of nintedanib in patients with non-IPF PF-ILD, we investigated its effects on the fibrosing functions of HLFs derived from patients with PF-hypersensitivity pneumonitis (PF-HP, n = 7), PF-sarcoidosis (n = 5) and pleuroparenchymal fibroelastosis (PPFE, n = 4). HLFs were treated with nintedanib (10 nM-1 μM) and then stimulated with PDGF-BB (25-50 ng/ml) or TGF-β1 (1 ng/ml) for 24-72 h to assess proliferation and migration or differentiation. At nanomolar concentrations, nintedanib reduced the levels of PDGF receptor and ERK1/2 phosphorylation, the proliferation and the migration of PF-HP, PF-sarcoidosis and PPFE HLFs stimulated with PDGF-BB. Moreover, nintedanib also attenuates the myofibroblastic differentiation driven by TGF-β1 but only when it is used at 1 μM. The drug reduced the phosphorylation of SMAD2/3 and decreased the induction of collagen, fibronectin and α-smooth muscle actin expression induced by TGF-β1. In conclusion, our results demonstrate that nintedanib counteracts fundamental fibrosing functions of lung fibroblasts derived from patients with PF-HP, PF-sarcoidosis and PPFE, at concentrations previously reported to inhibit control and IPF HLFs. Such effects may contribute to its clinical benefit in patients suffering from these irreversible ILDs.
Topics: Animals; Humans; Transforming Growth Factor beta1; Becaplermin; Lung Diseases, Interstitial; Lung; Fibrosis; Idiopathic Pulmonary Fibrosis; Fibroblasts; Sarcoidosis; Disease Progression
PubMed: 37972706
DOI: 10.1016/j.pupt.2023.102267 -
Frontiers in Immunology 2023Sarcoidosis is an inflammatory granulomatous disease of unknown etiology with predominant lung involvement. Organ involvement and disease severity, as well as the nature...
RATIONALE
Sarcoidosis is an inflammatory granulomatous disease of unknown etiology with predominant lung involvement. Organ involvement and disease severity, as well as the nature of immune alterations, vary among patients leading to a range of clinical phenotypes and outcomes. Our objective was to evaluate the association of disease course and immune responses in pulmonary sarcoidosis.
METHODS
In this prospective cohort study of 30 subjects, most of whom were followed for one year, we evaluated 14 inflammatory markers in plasma, 13 Treg/T cell flow cytometry markers and 8 parameters of FOXP3 Treg biology, including suppressive function, epigenetic features and stability.
RESULTS
We identified a set of 13 immunological parameters that differ in sarcoidosis subjects in comparison with healthy donors. Five of those were inversely correlated with suppressive function of Tregs in sarcoidosis, and six (TNFα, TNFR I and II, sCD25, Ki-67 and number of Tregs) were particularly upregulated or increased in subjects with thoracic lymphadenopathy. Treg suppressive function was significantly lower in patients with thoracic lymphadenopathy, and in patients with higher burdens of pulmonary and systemic symptoms. A combination of five inflammatory markers, Ki-67 expression, Treg function, and lung diffusion capacity evaluated at study entry predicted need for therapy at one year follow-up in 90% of cases.
CONCLUSION
Tregs may suppress ongoing inflammation at local and systemic levels, and TNFα, TNFR I and II, sCD25 and Ki-67 emerge as attractive biomarkers for sarcoid inflammatory activity.
Topics: Humans; T-Lymphocytes, Regulatory; Receptors, Tumor Necrosis Factor, Type I; Tumor Necrosis Factor-alpha; Prospective Studies; Ki-67 Antigen; Sarcoidosis; Prognosis; Forkhead Transcription Factors; Lymphadenopathy
PubMed: 38173720
DOI: 10.3389/fimmu.2023.1301991