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1
Harczy, Martha. "Lipid mediators in lung anaphylaxis." Mémoire, Université de Sherbrooke, 1988. http://hdl.handle.net/11143/11716.
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Abstract: Arachidonic acid and PAF are released from the lungs during anaphyIaxis. The aim of this study is to describe the kinetics of the release of eicosanoids and to observe the effects of selected ihhibitors and a PAF antagonist on their release. Isolated lungs of previously sensitized animals were perfused via the pulmonary artery and challenged with ovalbumin. Prostaglandin E21 throraboxane B2, 6-keto prostaglandin F1? levels were determined in aliquots of effluents with radioimmunoassay and/or enzyme immunoassay techniques whereas leukotrienes B4 and D4 were measured by reverse-phase high performance liquid chromatography. In selected experiments 12-HHT and 12-keto HT were measured in the lung effluents. The peak release of eicosanoids from the lungs ensued approximately at 4-6 minutes after the initiation of anaphylactic shock. Perfusion of the lungs with aspirin, indomethacin decreased the formation of cyclooxygenase products and there was no significant change in the release of LTB4, LTD4. BW755C and ETYA at high concentrations reduced the release of all eicosanoids from the lungs as did high concentrations of FPL55712. An antagonist of PAF (BN52021) produced a dose dependent inhibition of prostaglandins, thromboxane and leukotrienes from the anaphylactic lungs. Perfusion of PAF in non-sensitized lungs produced a release of eicosanoids, however the magnitude of the release was negligible compared to that of the release in anaphylactic shock. A Vitamin E analog inhibited the release of LT-s while did not inhibit the release of PG-S and TxB2. These, results emphasize on the complex interactions regulating the synthesis of arachidonic acid metabolites and an indirect role of PAF has been suggested.||Résumé: L'acide arachidonique et le PAF sont libérés par le poumon durant le choc anaphylactique. Le but de la présente étude est d'analyser la cinétique de la libération d'eicosanoïdes, et d'observer les effets de plusieurs inhibiteurs et d'un antagonistes du PAF sur leur libération. Le poumon de cobaye sensibilisé a été perfusé via l'artère pulmonaire et stimulé avec l'ovalbumine. La prostaglandine E2, la thromboxane B2, la prostaglandine 6-ceto-F1? ont été déterminées dans les échantillons de l'effluent avec un essai radioimmunologique ou avec une technique d'essai immunologique enzymatique alors que les leucotriènes B4 et D4 ont été mesurées par chromatographie liquide à haute performance en phase inversée. Dans certaines expériences, le 12-HHT et le 12-ceto-HT ont été mesurés dans l'effluent pulmonaire. Le pic de libération des eicosanoïdes a été observé approximativement 4-6 minutes après le début du choc anaphylactique. La perfusion du poumon avec l'aspirine et l'indométacine a diminué la formation des produits de la cyclooxygénase et n'a pas modifié la libération de leucotriènes B4 et de leucotriènes D4. Le composé BW755C, le ETYA ainsi que le FPL55712 utilisés à fortes concentrations ont réduit la libération de tous les eicosanoïdes du poumon. L'antagoniste du PAF (BN52021) a produit une inhibition dose-dépendante de la libération de prostaglandines, de thromboxanes et de leucotriènes par le poumon anaphylactique. Lorsque les poumons de cobayes non-sensibilisés ont été traités avec des injections de PAF, nous avons noté la libération d'eicosanoïdes. Cependant, la libération d'eicosanoïdes stimulée avec ce médiateur lipidique était beaucoup moindre que celle observée au cours du choc anaphylactique. Un analogue de la vitamine E a inhibé la libération de leucotriènes alors qu'il n'a pas inhibé de libération de prostaglandines et de thromboxanes. Ces résultats mettent en évidence les interactions complexes qui interviennent au cours de la synthèse des métabolites de l'acide arachidonique et le rôle complexe du PAF dans les réactions d'hypersensibilité et inflammatoires.
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Hernández, Muñoz Luis Ulises. "Smartphone tools for anaphylaxis management." Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/5695/.
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Anaphylaxis is a severe life-threatening allergic condition which is increasing in prevalence and now affects more than 2% of UK children. Anaphylaxis management requires the avoidance of allergen triggers and preparation in readiness for an anaphylactic reaction. People with anaphylaxis and their carers carry Adrenaline Auto-Injectors which need to be administered immediately in the event of an anaphylactic reaction. But, unfortunately, many people often do not know how to use the injectors and fail to use them or fail to use them correctly. This is due in part to deficiencies in training and also to a lack of a system encouraging continuous practice and providing feedback on that practice. Pervasive healthcare research has demonstrated potential in supporting the management of chronic conditions such as diabetes. However, research into assistive technologies for the support of anaphylaxis management has been significantly neglected. Thesis results provide evidence of the potential that smartphone tools have to significantly improve adrenaline injection training skills and a positive influence on self-efficacy. In addition, the results provide insights into possible self-efficacy failings in traditional training and benefits of embedding self-efficacy theory into the design process. The thesis also shows that clinical staff expressed positive feedback after they were provided the technology for one week.
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Balbino, Bianca. "Characterizing the role of IgG antibodies in anaphylaxis." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS024.
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L'anaphylaxie est la manifestation clinique la plus sévère de l’allergie. Il est couramment admis que chez l’homme, l’anaphylaxie est médiée par les anticorps de type IgE. Cependant, des données chez la souris indiquent que les IgG peuvent également contribuer à l’anaphylaxie. Le but de ma thèse a été de mieux comprendre comment les IgG induisent l’anaphylaxie. Dans un premier temps, nous avons démontré que les IgG murines induisent l’anaphylaxie en activant le récepteur FcγRIII à la surface des macrophages, ce qui aboutit à la libération de PAF. Nous avons ensuite voulu savoir si les IgG humaines peuvent également induire des chocs anaphylactiques. L’anticorps thérapeutique Omalizumab (IgG1 humanisée anti-IgE) induit des chocs anaphylactiques chez certains patients. Nous avons démontré que Omalizumab forme des complexes immuns qui peuvent activer les récepteurs FcγRs et induire des chocs anaphylactiques dans des souris exprimants les FcγRs humains (hFcγRKI). Nous avons ensuite développé une version mutante d’Omalizumab incapable de lier les FcγRs et démontré que cet anticorps bloque les IgE sans induire d’anaphylaxie. Finalement, nous avons développé un nouveau modèle humanisé d’anaphylaxie aux arachides dans lequel les souris hFcγRKI sont sensibilisées avec des IgG de patients allergiques aux arachiques. Nos données préliminaires indiquent que les IgG peuvent induire l’anaphylaxie dans ce modèle. De manière surprenante, l’anaphylaxie est augmentée dans des souris n’exprimant aucun FcγR. Nous étudions actuellement le(s) mécanisme(s) responsables de cet effet, et notamment l’implication de la voie du complément et le rôle du récepteur inhibiteur FcγRIIBAnaphylaxis is a severe and potentially fatal allergic reaction. The current paradigm in humans states that anaphylaxis is triggered by allergen-specific IgE antibodies (Abs). Several reports in mice indicate that IgG Abs can also trigger anaphylaxis. The goal of my thesis was to better understand the pathways through which IgG mediate anaphylaxis. We first evaluated this in an adjuvant-free mouse model of active systemic anaphylaxis. We observed a contribution of the 'classical’ pathway mediated by IgE, FcγRI, mast cells and histamine. However, anaphylaxis was largely mediated by an ‘alternative’ pathway driven by IgG, FcγRIII, macrophages and PAF. We then examined whether human IgG can also trigger anaphylaxis. Omalizumab, an IgG1 anti-IgE mAb, has been reported to induce adverse events, including anaphylaxis. We found that Omalizumab forms immune complexes with IgE that engage FcγRs and induce both skin inflammation and anaphylaxis when injected into mice expressing all human FcγRs (hFcγRKI). We then developed an Fc-engineered version of Omalizumab which cannot bind FcγRs, and demonstrated that this Ab is as potent as Omalizumab at blocking IgE-mediated allergic reactions, but does not induce FcγR-mediated anaphylaxis. Finally, I describe ongoing work in a new model of peanut anaphylaxis in which hFcγRKI mice are sensitized with IgG from allergic subjects. Preliminary data indicate that these IgG induce anaphylaxis in this model; Surprisingly, anaphylaxis is increased in mice deficient for all FcγRs. We are now investigating the mechanism(s), in particular the implication of the complement pathway, and the role of the inhibitory receptor FcγRIIB
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Gillis, Caitlin. "Neutrophils in IgG- and endotoxin-induced systemic inflammation : protective or pathological agents ?" Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066279/document.
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Les neutrophiles contribuent à l'inflammation protectrice et pathologique. Ce projet de thèse consiste à déterminer le rôle des neutrophiles dans des modèles d'inflammation systémique graves et potentiellement mortelles, induite par le lipopolysaccharide (LPS, endotoxémie) ou par des complexes immuns antigène-anticorps (anaphylaxie). L'anaphylaxie est une réaction allergique qui peut être IgE- et/ou IgG-dépendante. L’endotoxémie est un modèle pertinent de l'inflammation au cours de maladies graves. Pour étudier les neutrophiles in vivo, nous avons utilisé un nouveau modèle murin de neutropénie inductible. Nous montrons que les neutrophiles et la Myélopéroxidase qu’ils produisent ont un rôle protecteur dans le choc endotoxique, indépendamment de l'environnement microbiologique. A l'inverse, les neutrophiles peuvent contribuer à l'anaphylaxie induite par les IgG chez la souris. Comme les récepteurs pour les IgG (FcγR) murins sont très différents des humains, nous avons développé un modèle de souris knock-in dans lequel les FcγR murins a été remplacé par les FcγR humains, activateurs et inhibiteur. Chez ces souris, nous montrons que des IgG humaines peuvent induire une anaphylaxie: le FcγRIIA a un rôle dominant, via l'activation des neutrophiles, et les médiateurs PAF et histamine. En parallèle, nous développons un modèle murin d’anaphylaxie à un curare, le Rocuronium, utilisé en clinique. Au même temps, dans une étude clinique, les résultats d’analyses des échantillons sanguins des patients suspectés d’avoir subi une anaphylaxie au curare soutien notre hypothèse de travail: que l’activation des neutrophiles par des IgG spécifiques est impliquée dans l'anaphylaxie humaineNeutrophils are agents of protective and pathological inflammation. This thesis work aimed to determine the role of neutrophils during severe, potentially fatal models of systemic inflammation induced by lipopolysaccharide (LPS, endotoxemia) or by IgG immune complexes (anaphylaxis). Anaphylaxis is a severe allergic reaction that may proceed via IgE- or IgG-dependant pathways. Endotoxemia is a model relevant to inflammation during critical illness. To study neutrophils in vivo, we employed a new mouse model of inducible neutropenia. We found, surprisingly, that neutrophils and neutrophil-derived MPO protect against the severity of endotoxic shock, independently of the microbiological environment, suggesting that neutrophils limit inflammation during endotoxemia. Conversely, neutrophils can contribute to IgG-induced anaphylaxis in mice. As mice and human IgG receptors (FcγR) are very different, we developed a novel mouse strain in which targeted insertion of human FcγR into the murine loci recapitulated hFcγR expression. Herein, using these mice, this work demonstrates that anaphylaxis induced by hIgG proceeds within a native context of activating and inhibitory hFcγRs, and that neutrophil activation via FcγRIIA is a dominant pathological pathway, involving the mediators PAF and histamine. Finally, we describe ongoing development of a mouse model of anaphylaxis in response to Rocuronium, a curare-based neuromuscular blocking agent (NMBA). In addition, as part of a collaborative clinical study we analysed blood samples from patients suspected of NMBA-induced anaphylaxis, finding evidence for the activation of a neutrophil- and IgG-dependent axis during human anaphylaxis
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Wang, Yunguan. "Involvement of Complement in IgG2a-mediated Anaphylaxis." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1331300479.
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Fitzgerald, M. F. "The role of PAF-acether in guinea-pig anaphylaxis." Thesis, University of Sunderland, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.378070.
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Li, Jamma. "In vitro testing in the evaluation of perioperative anaphylaxis." Thesis, The University of Sydney, 2019. https://hdl.handle.net/2123/21355.
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Background Perioperative anaphylaxis is potentially life-threatening with an estimated incidence of 1:11,000 in Australia. The culprit agent is identified in 50-60% of cases. Neuromuscular blocking agents (NMBA) remain the leading cause. Standard evaluation in Australia comprises history, in vivo skin tests and in vitro specific IgE (sIgE) assays. Whilst drug provocation testing (DPT) to suspected NMBA culprits is the gold standard test for diagnosing or negating allergy, DPT is associated with significant risk particularly in this context. A few specialised international centres include an in vitro testing method known as basophil activation testing (BAT) as part of clinical assessment. BAT is a potentially useful in vitro test that is not commercially available in Australia or part of standard evaluation. Following diagnosis of NMBA anaphylaxis, identifying safe subsequent anaesthesia is critical. A patient with anaphylaxis to one NMBA may also have an allergic reaction to other NMBAs (cross-reactivity). Current standard practice in Australia to assess for cross-reactivity involves skin testing to other NMBAs available as there is significant risk with the use of DPT. Therefore, we sought to assess cross-reactivity by BAT, and examine its agreement with skin testing. Methods Our patient cohort was obtained from the Anaesthetic Allergy Clinic (AAC) at Royal North Shore Hospital, a service which receives referrals from the state of New South Wales for the evaluation of perioperative anaphylaxis, a severe allergic reaction during the perioperative period, which may be IgE or non-IgE mediated affecting at least one major organ system. All patients attending the AAC between May 2017 and July 2018, who received a NMBA during the perioperative episode qualified for the study. Patients received standard evaluation comprising clinical history, skin tests and specific IgE tests, including to morphine and pholcodine, plus BAT using CD63, CD203c and CD300a as surface activation markers. Results One-hundred-and-twenty patients were sequentially recruited from the AAC. Sixty-one patients were diagnosed with NMBA anaphylaxis and enrolled in the intervention arm. Fifty patients with a diagnosis other than NMBA anaphylaxis were enrolled in the control arm. A further nine patients had a clinical history suggestive of IgE-mediated anaphylaxis where no cause could be identified. BAT results were expressed as % upregulation above the negative control, and as a stimulation index (mean fluorescence index of stimulated sample divided by the negative control). We calculated cut-offs of 4.45% and 1.44 for CD63, and 8.80% and 1.49 for CD203c. Sensitivity using CD63 and CD203c was 77% with specificity 76%. A subgroup of 10 of 61 patients with NMBA anaphylaxis had no sensitisation on skin tests. BAT using CD63 and CD203c showed sensitisation in 6, and addition of CD300a to the testing strategy increased sensitisation to 9 patients. Cross-reactivity on skin testing was found in 31 of 61 patients with NMBA anaphylaxis. Sensitisation to a complete panel of NMBAs on skin testing and BAT only completely matched in 9 patients (15%). There was more sensitisation to pancuronium and cisatracurium on BAT (P<0.05). There was less sensitisation to rocuronium on BAT. Results of skin tests and BAT were comparable for vecuronium and suxamethonium (P<0.05). Conclusions BAT may a useful supplement to standard evaluation for diagnosing NMBA anaphylaxis in patients with suggestive histories but no sensitisation on skin tests. Ongoing study of this specific group of patients is required to clarify its utility in clinical practice. The potential role of BAT for identifying safe anaesthesia needs further evaluation. BAT detects a different cross-reactivity profile to skin tests. Negative skin testing and BAT may increase clinician confidence to perform DPT. We need further studies using DPT as well as follow-up of subsequent anaesthesia in our cohort to determine the clinical significance of BAT sensitisation.
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Lohman, Isabelle Carlotta 1948. "THE PRODUCTION AND PURIFICATION OF RABBIT SERUM IMMUNOGLOBULIN-E, AND THE ROLE OF IMMUNOGLOBULIN-E IN SYSTEMIC ANAPHYLAXIS." Thesis, The University of Arizona, 1987. http://hdl.handle.net/10150/291183.
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Dunn, Anita Marie 1956. "The role of neutrophils in systemic anaphylaxis in the rabbit." Thesis, The University of Arizona, 1989. http://hdl.handle.net/10150/276960.
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The objective of this study was to determine whether neutrophils play a significant role in anaphylaxis or in the response to the anaphylactic mediator platelet activating factor (PAF) in the rabbit. Vinblastine and anti-neutrophil antibodies were compared as neutrophil depleting agents, and 0.35 mg/kg vinblastine was selected as optimal for efficiency and specificity of depletion. Anaphylaxis was induced in sensitized rabbits by intravenous antigen challenge. Neutrophil depletion to 399 ± 101 cells/mm³ blood (14 ± 3%) did not significantly inhibit the physiologic and hematologic events associated with anaphylaxis except tachycardia. However, vinblastine pretreatment significantly reduced tachycardia and the right ventricular pressure increase and abolished the increase in pulmonary resistance caused by intravenous PAF. We conclude that although neutrophils do not play a significant role in IgE-anaphylaxis, they are important in the PAF-induced increases in right ventricular pressure and pulmonary resistance. PAF may not be a major mediator of these two physiologic alterations in IgE-anaphylaxis.
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Rastogi, Shruti. "The Role of Prostaglandin E2 in causing susceptibility towards Anaphylaxis." Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/21632.
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Die Ausbildung und der Schweregrad einer Anaphylaxie kann durch verschiedene Co-Faktoren beeinflusst werden. Zu diesen zählen die nichtsteroidalen Antiphlogistika (NSAIDs), die ihre Wirkung über die Inhibition der COX entfalten. Wie NSAIDs den Schweregrad der Anaphylaxie beeinflussen, ist bisher nicht genau bekannt. Interessanterweise zeigen Anaphylaxie-Patienten mit einer NSAID-Hypersensibilität niedrige Konzentrationen des regulatorischen Prostaglandins E2 (PGE2). Zudem zeigen ASA-tolerante und –intolerante Asthma-Patienten variable anaphylaktische Sensitivitäten.
Anhand der vorliegenden Arbeit sollte untersucht werden, ob sich eine PGE2-Dysregulation auf die Ausbildung und den Schweregrad der Anaphylaxie auswirkt und ob diese durch genetische Prädispositionen gefördert werden kann.
Dazu wurden zunächst die PGE2 Konzentration im Serum von ANA-Patienten und gesunden Individuen gemessen. ANA-Patienten zeigten reduzierte PGE2 Level, die invers mit dem Schweregrad der ANA korrelierten. Unterstützend weisen zwei in der Allergieforschung häufig verwendete Mauslinien, Balb/c und C57BL/6, unterschiedliche PGE2 Level auf, die wiederum invers mit dem ANA-Schweregrad korrelierten. Eine Stabilisierung der PGE2 Konzentration mittels eines pharmakologischen Inhibitors der Hydroxyprostaglandin-Dehydrogenase (15-PGDH-I) in vivo führte zu einer Verbesserung des ANA Schweregrades. Um in diesem Zusammenhang den Einfluss von ASA und PGE2 besser zu verstehen, wurde das Model der systemisch passiven ANA im Mausmodel eingesetzt. ASA verschlimmerte den Schweregrad der ANA durch die Inhibition der COX1/2. PGE2 konnte diese Verschlimmerung über die EP Rezeptoren 2, 3 und 4 reduzieren. Um die zugrundeliegenden Mechanismen der Wirkweise von exogenem PGE2 und EP-Agonisten besser zu verstehen, wurden diese Zusammenhänge in murinen und humanen Mastzellen untersucht. PGE2 reduzierte die Schwere der ANA durch Inhibition der Mastzell-Aktivität in diesem System über die Rezeptoren EP2 und EP4.
Anhand der vorliegenden Arbeit konnte gezeigt werden, dass bereits homöostatische PGE2 Konzentrationen die Aktivität der Mastzelle verändern und vor einer schweren ANA schützen. Zudem kann der Grad der ANA und der Einfluss des PGE2 auf die Mastzellantwort durch genetische Prädisposition beeinflusst werden. Die pharmakologische Stabilisierung des PGE2 könnte daher eine vielversprechende, therapeutische wie auch vorbeugende Strategie zur Behandlung risikoreicher ANA- Patienten sein.The clinical outcome of anaphylaxis (ANA) can be affected by several co-factors. Non-steroidal anti-inflammatory drugs (NSAIDs) are well-known co-factors of ANA acting via COX-inhibition. The NSAIDs-mediated mechanisms altering the severity of ANA are not well-defined. It is reported that patients of ASA (NSAID)-hypersensitivity show low levels of the regulatory prostaglandin E2 (PGE2). Moreover, the effectiveness of PGE2 administration in such patients suggests a critical role of PGE2 in ASA hypersensitivity. In addition, patients of ASA-tolerant and ASA-intolerant asthma show variable ANA sensitivities suggesting a role of genetic variation in susceptibility. The aim of this thesis was to study whether and how PGE2 dysregulation predisposes to ANA and whether genetic pre-dispositions affect the PGE2 system and therefore ANA susceptibility. First, sera from ANA patients and healthy individuals were analyzed for PGE2 levels. ANA patients were characterized by reduced PGE2 levels which inversely correlated with the severity of ANA. This disparity was confirmed by differential PGE2 levels between Balb/c and BL/6 strains, two genetic mouse strains frequently employed in allergy research. PGE2 levels in these mice were again inversely related with the severity of ANA. Results were confirmed by in vivo PGE2 stabilization using 15-hydroxyprostaglandin dehydrogenase inhibitor (15-PGDH-I). Pharmacological PGE2 stabilization ameliorated ANA severity in mice. A passive systemic ANA (PSA) model was applied to study the impact of ASA on ANA severity and the role of PGE2 in this context. ASA aggravated ANA by inhibiting COX-1/COX-2, while PGE2 reduced the aggravation through EP receptors 2, 3 and 4. To delineate the underlying mechanisms, murine and human mast cells were used to study the impact of exogenous PGE2 and EP agonists. PGE2 attenuated ANA severity by inhibiting MC activation through EP2 and EP4 receptors and interfering with MC signaling. In summary, this thesis demonstrates that homeostatic levels of PGE2 modulate MC activation and protect against ANA severity. The impact of PGE2 on MC responses and ANA susceptibility is governed by genetic variation. Pharmacological stabilization of PGE2 may prove to be a therapeutic or preventive strategy in the management of high-risk ANA patients.
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Brown, Simon Geoffrey Archer, and simon brown@uwa edu au. "Preventing anaphylaxis to venom of the jack jumper ant (Myrmecia pilosula)." Flinders University. School of Medicine, 2003. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20050707.103356.
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Background: Myrmecia pilosula (the jack jumper ant, JJA) is the principal cause of ant venom
anaphylaxis in Australia. Whereas honeybee and wasp venom allergy can be treated by venom
immunotherapy (VIT), no such treatment is available for ant sting allergy. In addition, information on the natural history of JJA sting allergy is required to identify those most likely to benefit from immunotherapy. The main objectives of this research were to establish: (i) the prevalence, natural history and determinants of reaction severity for JJA allergy, and; (ii) the efficacy and tolerability of JJA VIT.
Methods: A search of the Royal Hobart Hospital (RHH) forensic register, a random telephone survey, and a review of emergency department (ED) presentations were performed. Three hundred eighty-eight JJA allergic volunteers were assessed, including serum venom-specific IgE
RAST, and then followed up for accidental stings over a 4-year period. Finally, a randomised
double-blind, placebo-controlled, crossover trial of JJA VIT was performed. Laboratory parameters
measured during the trial were; leukocyte stimulation index (SI), IL-4 production, IgE RAST, histamine release test (HRT), leukotriene release test (LRT) and basophil activation test (BAT). Intradermal venom skin testing (VST) was also performed at trial entry.
Findings: The prevalence of JJA sting allergy was 2.7% in the Tasmanian population, compared to 1.4% for honeybee. People aged 35 or older had a greater risk of both sting allergy and hypotensive reactions. Four deaths were identified, all in adults with significant comorbidities. During follow-up, 79 (70%) of 113 accidental jack jumper stings caused systemic reactions. Only prior worst reaction severity predicted the severity of follow-up reactions, with the majority of people experiencing similar or less severe reactions when stung again. Sixty-eight otherwise healthy JJA allergic adult volunteers were enrolled in the clinical trial. Systemic reactions to therapy were recorded in 34% during VIT. Objectively defined systemic reactions to sting challenges arose in 1/35 after VIT (mild self-limiting urticaria only) versus 21/29 in the placebo group. Treatment with oxygen, intravenous adrenaline infusion and volume resuscitation was effective and well tolerated. Hypotension was always accompanied by a relative bradycardia, which was severe and treated with atropine in two patients. In the placebo group, only VST and HRT were predictive of sting challenge results. Although IgE RAST, leukocyte SI and IL-4 production, LRT and BAT all correlated well with VST, they did not predict sting challenge outcome. After successful VIT, venom-induced leukocyte IL-4 production tended to fall, whereas IgE RAST increased and a natural decline in HRT reactivity was reversed.
Interpretation: VIT is highly effective in prevention of JJA sting anaphylaxis and is likely to be of most benefit to people with a history of severe systemic reactions, which usually occur in people aged over 35. Neurocardiogenic mechanisms &/or direct cardiac effects may be important factors in some anaphylaxis deaths. Systemic reactions to immunotherapy are common and require immediate access to resuscitation facilities. The HRT warrants further investigation as a test for selecting those most likely to benefit from VIT. None of the tests evaluated appear to be reliable markers of successful VIT.
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Norton, Sarah. "Fullerene C70 derivatives dampen anaphylaxis and allergic asthma pathogenesis in mice." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/2759.
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Fullerenes are carbon nanospheres that can be solublized by the addition of polar chemical groups to the carbon cage, forming fullerene derivatives. One specifically derivatized fullerene compound, termed C70-Tetragylocolate (C70-TGA), has been shown to stabilize mast cell responses in vitro thus we hypothesized it may have an effect on mast cell-driven diseases such as asthma and systemic anaphylaxis. To observe the effects of C70-TGA on systemic anaphylaxis, mice were subjected to a model of passive systemic anaphylaxis. In this model, mice were injected with DNP-specific IgE 16 hours prior to challenge, then treated with C70-TGA. Immediately prior to DNP challenge, mice were subjected to a second injection of C70-TGA. Following DNP challenge, body temperature was recorded and blood was collected for quantitation of histamine levels. Treatment with C70-TGA significantly reduced body temperature drop associated with systemic anaphylaxis and serum histamine levels. To observe the effects of C70-TGA on chronic features of asthma in vivo, we utilized a heavily MC influenced model of asthma pathogenesis. Mice were sensitized by intraperitoneal (i.p.) injection of ovalbumin (OVA) in saline, challenged intranasally (i.n.) with OVA, and one of two treatment strategies was pursued. In one, C70-TGA was given i.n. throughout disease development. In the other, C70-TGA was given following an initial set of challenges to allow disease to develop prior to treatment; mice were then re-challenged with OVA to assess the effect on established disease. We found that C70-TGA treatment significantly reduced airway inflammation and eosinophilia and dramatically reduced bronchoconstriction in either model. Cytokines IL-4 and IL-5 and serum IgE levels are significantly reduced in C70-TGA treated animals. Interestingly, we also saw an increase in the anti-inflammatory eicosanoid 11, 12-epoxyeicosatreinoic acid (11,12-EET) in the BAL fluid, suggesting the involvement of this mediator in C70-TGA inhibition. Further experiments utilizing an inhibitor of 11,12-EET formation (6-(2-Propargyloxyphenyl)hexanoic acid) and a structural analog of 14,15-EET (14,15-EE-5(Z)-E) in vivo indicate that these mediators are closely associated with C70-TGA mediated inhibition as their inhibition reverses the anti-inflammatory effects of C70-TGA. Importantly, mice did not exhibit any acute toxicity following C70-TGA treatment and liver and kidney function were normal. Collectively, these results show that the fullerene C70 derivative C70-TGA is capable of dampening severe allergic responses including systemic anaphylaxis, airway inflammation, and bronchoconstriction. The mechanism of inhibition is through the upregulation of the anti-inflammatory EETs, which may dampen mast cell degranulation in vivo, thus contributing to the inhibitory effect of C70-TGA on allergic disease.
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Nemali, Sailasree. "Molecular and functional characterization of bovine C5a receptor." Thesis, Montana State University, 2006. http://etd.lib.montana.edu/etd/2006/nemali/NemaliS0506.pdf.
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Wiese, Anne Carroll Gordon 1956. "MEDIATORS OF IgE-INDUCED ANAPHYLAXIS: AN IN VITRO STUDY OF MEDIATORS CAUSING CONTRACTION OF RABBIT PULMONARY ARTERY." Thesis, The University of Arizona, 1987. http://hdl.handle.net/10150/291622.
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Rabbits were immunized such that antibodies of the IgE class were preferentially produced. Normal rabbit pulmonary artery sections were challenged with supernatant from antigen-treated sensitized blood cells in the presence of antagonists. The hypothesis is that mediators capable of contracting pulmonary arteries are released from blood cells when blood cells are challenged with antigen. Possible mediators are histamine, serotonin, indomethacin and LTD4. Chlorpheniramine (2.6 x 10⁻⁵M) with methysergide (1 x 10⁻⁵ produced a one-hundred-twenty-fold inhibition of contraction. Chlorpheniramine with FPL-55712 (1 x 10⁻⁵M) did not significantly alter the response seen with chlorpheniramine alone. When supernatant obtained from sensitized blood cells pretreated with 1 x 10⁻⁵ indomethacin was used to challenge muscle rings in the presence of chlorpheniramine the response was also not significantly different from response seen with chlorpheniramine alone. Histamine contracted pulmonary artery. Chlorpheniramine (2.6 x 10⁻⁵ inhibited the response six-hundred-fold. Serotonin also contracted pulmonary artery. Methysergide (10⁻⁵M) blocked the response seven-hundred-fold.
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Lee, Sangil. "Incidence of anaphylaxis and epinephrine autoinjector prescribing trends| A population based study." Thesis, College of Medicine - Mayo Clinic, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10111495.
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Anaphylaxis is a potentially life-threatening systemic allergic reaction [1]. We aimed to determine the overall anaphylaxis incidence rate, the incidence of specific causes of anaphylaxis over time, and epinephrine auto-injector prescribing trends in Olmsted County, Minnesota.
Using the resources of the Rochester Epidemiology Project, a comprehensive records linkage system, we performed a population-based incidence study in Olmsted County, Minnesota, from 2001 through 2010. All cases with a diagnosis of anaphylactic shock and 20% of cases diagnosed with venom/bee sting, food allergy, and medication reactions were manually reviewed. Anaphylaxis incident cases were required to meet the National Institute of Allergy and Infectious Disease / Food Allergy and Anaphylaxis Network (NIAID/FAAN) diagnostic criteria. We also extracted all outpatient epinephrine prescriptions for all Olmsted County residents during 2003-2010 to further explore treatment of anaphylaxis. The sampling faction was accounted for in determining the reported number of anaphylaxis incidence cases. Incidence rates per 100,000 person-years were calculated using the adjusted number of incident cases of anaphylaxis (and likewise the number patients with a prescription) as the numerator and age- and sex-specific counts of the population of Olmsted County as the denominator. The relationships of age group, sex, and year of anaphylaxis with incidence rates were assessed by fitting Poisson regression models using the SAS procedure GENMOD.
We identified six hundred and thirty-one cases of anaphylaxis (51% male). The median age was 31 years (interquartile range 19-44). Incidence rates differed by year of diagnosis (p<0.001) and by age group (p<0.001). The overall age- and sex-adjusted incidence rate was 42 (95%CI 38.7 - 45.3) per 100,000 person-years. Four hundred and sixty eight cases (74%) of anaphylaxis were evaluated in the emergency department, 71 cases (11%) were admitted to the emergency department observation unit, and 92 cases (15%) were admitted to the hospital. Prescription data showed that the overall age- and sex-adjusted incidence rate of epinephrine prescriptions was 330 per 100,000 person-years (95% CI 320-340). Age-adjusted incidence rates for women and men were 369 (95% CI 354-385) and 288 (95% CI 274-302) per 100,000 person-years, respectively. Prescription incidence rates differed by year of diagnosis (p<0.001), age group (p<0.001), and sex (p<0.001). The incidence rate of outpatient prescription decreased by year during 2003-2005 then became constant during 2005-2010.
Our master’s degree thesis concludes that the overall anaphylaxis incidence rate was 42 per 100,000 person-years during 2001-2010 in the Olmsted County. The food, venom, and medication were the leading causes for anaphylaxis for younger age, middle age and the elderly, respectively. The majority of anaphylaxis cases were treated in the emergency department. The incidence rate of outpatient epinephrine prescriptions, which was 330 per 100, 000 person-years, decreased from 2003-2005 and reached plateau. Our study used updated diagnostic criteria for anaphylaxis and epinephrine prescription to demonstrate the flattening of the incidence. We would like to emphasize the clinicians to be aware of trend of anaphylaxis and supply of epinephrine in the community.
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Rastogi, Shruti [Verfasser]. "The Role of Prostaglandin E2 in causing susceptibility towards Anaphylaxis / Shruti Rastogi." Berlin : Humboldt-Universität zu Berlin, 2020. http://d-nb.info/121509566X/34.
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Beutier, Héloïse. "Plaquettes et neutrophiles : acteurs clés dans le choc allergique dépendant des IgG." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066519/document.
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Le choc anaphylactique est une réaction allergique systémique qui survient en quelques minutes et pouvant être fatale. Mon travail de thèse s’articule autour de deux projets dont la finalité est de mieux comprendre le mécanisme physiopathologique. La première partie de ce travail consiste à étudier in vivo chez la souris les contributions des récepteurs Fc aux IgG (FcγRs), des cellules effectrices et des médiateurs contribuant dans un modèle d’anaphylaxie systémique passive induit par une sous-classe particulière d’IgG : des IgG1, des IgG2a ou des IgG2b monoclonales dirigées contre un même antigène. Cette étude a permis de démontrer que le FcγRIII, les neutrophiles et les monocytes/macrophages sont les acteurs majoritaires quelque soit la sous-classe d’IgG de souris ; en revanche, la participation des basophiles ainsi que la contribution relative des médiateurs histamine et PAF sont dépendantes de la sous-classe d’IgG utilisée. La deuxième partie de ce travail consiste à étudier plus particulièrement la population plaquettaire dans un modèle de souris humanisées. Contrairement à la souris, les plaquettes humaines expriment un FcγR, le FcγRIIA déjà identifié comme acteur clé de l’anaphylaxie. Un modèle de choc allergique induit par des IgG humaines dans des souris transgéniques pour le FcγRIIA m’a permis de tester l’hypothèse suivant laquelle les plaquettes participent à l’initiation et/ou à la propagation de la réaction. Ce modèle a permis de mettre en évidence une thrombocytopénie sévère, des complexes plaquettes-leucocytes circulants et de montrer que le transfert de plaquettes ou de leur surnageant restaure les signes cliniques du choc allergiqueAnaphylaxis is a systemic hyperacute allergic reaction that occurs within minutes and can be fatal. The aim of my PhD project is to investigate the physiopathological mechanisms underlying anaphylaxis induction. The first part of my work focused on the contribution of FcγRs, effector cells and mediators in passive murine models of systemic anaphylaxis induced by the different subclasses of mouse specific IgG ; directed against the same antigen: IgG1, IgG2a or IgG2b. This study demonstrated that FcγRIII, neutrophils and monocytes/macrophages are the key players of anaphylaxis induction whatever the mouse IgG subclasses used. On the contrary, basophil participation and the relative contribution of histamine and PAF are IgG subclass dependent. The second part of this work examined the role of platelets in anaphylaxis using a humanized mouse model. Opposing the murine situation, human platelets express an IgG receptor, FcγRIIA. This receptor has already been identified as a key player in anaphylaxis. Using aggregated human IgG to induce anaphylaxis in mice transgenic for FcγRIIA, we tested our hypothesis that platelets contribute to the initiation and/or the propagation of this reaction. Anaphylaxis in this model was accompanied by a severe thrombocytopenia, the presence of circulating platelet-leukocyte complexes and activated platelets. I further demonstrated that the transfer of platelets or their activated supernatent into resistant mice restored features of anaphylactic shock
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Granger, Vanessa. "Etude de la nétose du polynucléaire neutrophile dans deux modèles de réactions allergiques : le choc anaphylactique aux curares et l’asthme." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS364.
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La nétose du polynucléaire neutrophile (PN) correspond à la libération de filaments d’ADN recouverts de protéines appelés Neutrophil Extracellular Trap (NETs). Outre leur rôle anti-infectieux, les NETs représentent des acteurs émergents de nombreuses pathologies inflammatoires et nous avons souhaité évaluer leur implication au cours de réactions allergiques.Au cours d’une étude clinique multicentrique notre équipe a mis en évidence un mécanisme alternatif de l’anaphylaxie aux curares, impliquant les PN. La phase aiguë de ces réactions s’accompagne d’une libération de NETs dont la concentration est corrélée avec la sévérité et avec une diminution de l’expression des récepteurs activateurs des IgG à la surface des PN (FcγRs) ; ceci suggère un rôle des complexes immuns (CI) IgG/curares dans la formation des NETs au cours de ces réactions anaphylactiques.Pour confirmer cette hypothèse, la capacité d’activation de la nétose par les CI IgG a été étudiée, via la mise au point d’un modèle de stimulation in vitro des PN humains purifiés.Ce travail montre que 2 récepteurs aux IgG du PN (FcγRIIa et FcγRIIIB) contribuent à la libération de NETs en réponse à différents types de CI.En parallèle, la formation des NETs a été explorée dans un modèle de réaction allergique chronique, l’asthme. Au niveau systémique, la concentration de NETs est associée à la présence d’un asthme sévère mal contrôlé et d’une obstruction bronchique peu réversible. Inversement, la concentration de NETs dans le lavage broncho-alvéolaire est plus élevée au cours de l’asthme modéré et semble traduire un recrutement pulmonaire et une activation des PN en réponse à une colonisation microbienne.Au total nous montrons que les NETs sont libérés au cours des deux modèles de réactions allergiques choisis, aiguë (anaphylaxie aux curares) et chronique (asthme) et qu’ils pourraient représenter des biomarqueurs de sévérité. Des travaux complémentaires sont nécessaires pour déterminer dans quelle mesure les NETs contribuent à la physiopathologie des allergiesNeutrophil netosis consists in the release of extracellular DNA filaments bound to granular proteins, called Neutrophil extracellular traps (NETs). In addition to their anti-infectious role, NETs are emerging actors of many inflammatory diseases and we decided to investigate their involvement during allergy.In a multicenter clinical study, our team highlighted an alternative mechanism of anaphylaxis to neuromuscular blocking agents (NMBA) involving neutrophils (PN). The acute phase of these reactions is characterized by NETs release which level is correlated with severity and with a decrease in IgG activating receptors (FcγRs) expression on PN; this suggests a role of immune complexes (IC) IgG / NMBA in NETs formation during these anaphylactic reactionsTo confirm this hypothesis, the ability of IgG ICs to activate netosis was studied through the development of an in vitro stimulation model of purified human PNs.This work shows that two PN IgG receptors (FcγRIIa and FcγRIIIB) contribute to NET release upon cellular activation by different ICsIn parallel, NETs formation has been explored in a model of chronic allergic reactions, asthma. At systemic level, NETs levels are associated with severe and poorly controlled asthma as well with the presence of low reversible bronchial obstruction. Conversely, NETs levels in bronchoalveolar lavage are higher in moderate asthma and appear to reflect pulmonary recruitment and activation of PN in response to microbial colonization.Taking together these results show that NETs are released during the two selected models of allergic reactions : acute (NMBA anaphylaxis) and chronic (asthma) and could be used as biomarkers of severity. Furthers works are needed to determine to what extent NETs contribute to the pathophysiology of allergy
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Alqurashi, Waleed. "Management of Children with Anaphylaxis in the Emergency Department: Practice Pattern and Prediction of Biphasic Reactions." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32101.
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This research aims to assess the practice pattern of Canadian emergency physicians for management of anaphylaxis and investigate the clinical predictors for biphasic reactions in children with anaphylaxis. We conducted two studies: a national survey and a multicenter Health Records (HR) review of emergency department visits. Of the 608 physicians surveyed, 340 (56%) responded. Overall, 211(62%) of the physicians correctly agreed that both hypothetical scenarios in the survey were consistent with anaphylaxis, and 206(61%) chose to administer epinephrine. In our HR review, we found five independent predictors of biphasic reactions: age 6-9 years (OR 3.60; 95% CI 1.5-8.58), time from onset of the anaphylactic reaction to ED presentation >90 minutes (OR 2.58; 95% CI 1.47-4.53), wide pulse pressure at triage (OR 2.92; 95% CI 1.69-5.04), treatment of the reaction with >1 dose of epinephrine (OR 2.7; 95% CI 1.12-6.55), and administration of inhaled salbutamol in ED (OR 2.39; 95% CI 1.24-4.62).
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Patel, Dipen. "Assessing Economic and HRQL Burden of Food Allergy and Anaphylaxis in the U.S." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2220.
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Background: Food allergy, an abnormal immunologic response to food protein, has an estimated prevalence of 6% in young children and 3.7% in adults in the U.S. The only proven therapy for food allergy is strict elimination of the offending allergens. As a result, caregivers and patients could experience constant anxiety and stress that affects their quality of life. Additionally, food allergy can lead to significant economic impact on the health care system, since severe reactions often lead to ED visits and hospitalizations. Objectives: The first major objective was to determine the economic burden of Food Allergy and Anaphylaxis (FAA) patients in the U.S. by estimating the direct medical and indirect costs. The second principal objective involved assessing the Health Related Quality of Life (HRQL) of food allergic patients by measuring their health utilities and disease specific quality of life. Methods: Economic burden was estimated by measuring certain direct medical and indirect costs from a societal perspective. Costs were estimated using a bottom-up approach -- calculating the average cost of illness per patient and multiplying it by reported prevalence estimates. FAA patients with an emergency department (ED) visit, office based physician visit, outpatient department visit, and hospital admission were identified from a list of federally administered databases using ICD-9 codes. Sensitivity analyses were conducted to measure the robustness of the estimates. The cross-sectional HRQL study measured health utilities in food allergic adults and children, and quality of life in allergic adults using EQ-5D and FAQL-AF questionnaires respectively. These questionnaires were administered in an online survey format. Regression models were specified to explore the deviations in HRQL scores between patients with different disease related characteristics. Results: The findings reveal that for a given year (2007), direct medical costs worth $225 million and indirect costs worth $115 million were incurred. Owing to the irregularities in the reporting and diagnosis of food allergy, these values might be an underestimation. Simulations from probabilistic sensitivity analysis generated mean direct medical costs of $307 million and indirect costs of $203 million. Survey responses were collected online for eight months, during which 45 adults and 94 parents (acting as proxy for their food allergic child) responded. Adults reported a mean utility of 0.874 compared to 0.918 for children. Gender, number of food allergies and frequency of carrying epinephrine device had significant impacts on HRQL scores. An effect size of 0.003 was estimated comparing health utilities of food allergic adults with the general U.S. population. Conclusions: This was the first research to examine economic burden of FAA, and elucidate health utilities for food allergic patients. A large proportion of costs were incurred due to ambulatory visits. Effect size calculation revealed that health utilities of food allergic patients were very similar to the general U.S. population.
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Gouel-Chéron, Aurélie. "Nouvelles approches diagnostiques du choc anaphylactique aux curares." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066289/document.
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Etablir le diagnostic d'une réaction d'hypersensibilité aiguë (RHA) peropératoire est difficile du fait de l'incidence supérieure des diagnostiques différentiels. Les facteurs de risques en sont mal établis. Il n'existe pas de signe clinique fiable aidant à un diagnostic rapide. Alors que 25% des explorations immunologiques classiques ne mettent pas en évidence un mécanisme IgE-médié, des études animales et humaines suggèrent un rôle des IgG dans ces RHA non caractérisées. Ce travail s'est basé sur deux cohortes de patients : la première pour étudier des phénotypes en lien avec l'apparition d'un bronchospasme, la seconde pour analyser des marqueurs diagnostiques au bloc opératoire et explorer un mécanisme alternatif impliquant les IgG. La survenue d'un bronchospasme au cours d'une RHA peropératoire n'est pas associée à un antécédent d'asthme mais au curare comme agent étiologique. La mise en évidence de la valeur diagnostique d'une hypocapnie inférieure à 20 mmHg dans le caractère sévère de la RHA devrait aider les cliniciens à l'établissement rapide du diagnostic. La présence d'IgG spécifiques anti-curares était associée à la survenue d'une RHA sévère suggérant une participation des IgG à la gravité de la RHA en association avec les IgE. En fonction du curare administré, le mécanisme de la RHA semble différent : implication d'anticorps (IgE et/ou IgG) dans 90% pour succinylcholine et rocuronium mais uniquement 50% pour atracurium suggérant une importante contribution de l'histamino-libération dans ces réactions. L'ensemble de ces travaux devraient permettre d'améliorer les performances diagnostiques en temps réel et à distance lors de la survenue d'une RHA peropératoireDiagnosis of intra-anesthetic acute hypersensitivity reactions (AHR) is challenging because of elevated incidences of differential diagnoses. Risk factors remain mostly unknown and there is no reliable clinical sign to help physicians in establishing a rapid diagnosis. In 25% of cases, immunologic exploration cannot identify the culprit agent through the exploration of the IgE-mediated pathway. Several animal and human studies suggest a role of IgG in the physiopathology of anaphylaxis, which could explain these uncharacterized AHR. This PhD has focused on two cohorts of patients: the first cohort allowed the exploration of phenotypic links in relation to bronchospasm occurrence; the second cohort analyzed clinical markers of severe AHR and the alternative pathway involving IgG against neuromuscular blocking agents (NMBA). Analysis of risk factors identified a NMBA as the culprit agent of the intra-anesthetic AHR to be the only factor statistically associated with bronchospasm. We propose that a hypocapnia below 20 mmHg may be a novel and useful tool for physicians for the rapid diagnosis of severe intra-anesthetic AHR. Among the second cohort of patients, NMBA-specific IgG were identified and associated with clinical severity, suggesting that they may participate in the severity of NMBA-AHR in association with IgE. The chemical structure of a given NMBA may dictate the mechanism of anaphylaxis to this particular NMBA: an IgE/IgG-pathway for succinylcholine and rocuronium, whereas atracurium may be rather linked to spontaneous histamine release mechanisms. Altogether, our results might improve diagnosis efficacy at the time of the AHR and during immunologic explorations
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Dinsmore, Kristen G., Bethany Campbell, Timothy Archibald, Greg Mosier, Stacy D. Brown, and Alexei Gonzalez-Estrada. "Refrigerated Stability of Diluted Cisatracurium, Rocuronium, and Vecuronium for Skin Testing after Perioperative Anaphylaxis." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/5266.
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RATIONALE: The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely cisatracurium, rocuronium, and vecuronium, for skin prick/intradermal testing.
METHODS: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, and 100,000x as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed and compared to a freshly prepared set of reference dilutions.
RESULTS: The results are measured as beyond use date (BUD) defined as recovery of drug versus the reference (90-110%). Based on the LC-MS/MS data, the BUD for cisatracurium diluted to 10x and 100x is 96 hours. Higher dilutions (1,000x to 100,000x) should be used immediately following preparation (within less than 24 hours). Vecuronium at 10x and 100x also has a BUD of 96 hours, and the 1,000x dilution is stable for 24 hours. The 10,000x dilution should be used immediately. Rocurium at 10x to 1,000x has a BUD of 48 hours, yet higher dilutions (10,000x and 100,000x) should be used immediately.
CONCLUSIONS: With increasing dilution factors, the stability of these drugs in saline decreases, increasing deviation between samples and references. The most stable dilutions for each of the drugs tested were 10x and 100x. Stability of these drugs is likely compromised by hydrolysis of the ester bonds in the drug molecules.
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Dinsmore, Kristen, Bethany Campbell, Timothy Archibald, Greg Mosier, Stacy PhD Brown, and Alexei MD Gonzalez-Estrada. "Refrigerated Stability of Diluted Cisatracurium, Rocuronium, and Vecuronium for skin testing after perioperative anaphylaxis." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/146.
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Rationale: The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely cisatracurium, rocuronium, and vecuronium, for skin prick/intradermal testing.
Methods: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed and compared to a freshly prepared set of reference dilutions.
Results: The results are measured as beyond use date (BUD) defined as recovery of drug versus the reference (90-110%). Based on the LC-MS/MS data, the BUD for cisatracurium diluted to 10x and 100x is 96 hours. Higher dilutions (1,000x to100,000x) should be used immediately following preparation (within less than 24 hours). Vecuronium at 10x and 100x, also has a BUD of 96 hours, and the 1,000x dilution is stable for 24 hours. The 10,000x dilution should be used immediately. Rocuronium at 10x to 1,000x has a BUD of 48 hours, yet higher dilutions (10,000x and 100,000x) should be used immediately.
Conclusions: With increasing dilution factors, the stability of these drugs in saline decreases, increasing deviation between samples and references. The most stable dilutions for each of the drugs tested were 10x and 100x. Stability of these drugs is likely compromised by hydrolysis of the ester bonds in the drug molecules.
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Sheikh, Aziz. "Key issues in the epidemiology and primary care management of allergic rhinitis, asthma and anaphylaxis." Thesis, Imperial College London, 2002. http://hdl.handle.net/10044/1/8247.
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Reilly, Karen Margaret. "Biochemical studies on heparin-like glycosaminoglycans from basophils and mast cells in allergy and anaphylaxis." Thesis, University of Edinburgh, 1988. http://hdl.handle.net/1842/26873.
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Manmohan, Manisha [Verfasser], and Thilo [Akademischer Betreuer] Jakob. "Follow up care of patients in southwest Germany with a history of Hymenoptera venom anaphylaxis." Freiburg : Universität, 2017. http://d-nb.info/1147680965/34.
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Guo, Yancai. "Role of mast cell-derived mediators for leukocyte/endothelium-interactions and microvascular mechanisms in inflammation and in anaphylaxis /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-457-7.
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Shipley, Jordan. "Seeking a Respec(table) Environment: A Phenomenological Inquiry into Pre-Service Teachers’ Lived Experience of Anaphylaxis." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32164.
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This phenomenological inquiry delved into the lived experience of what it is like to have anaphylaxis, a severe and potentially fatal allergy, for those in the teacher education context. Hence, an understanding of the phenomenon of living with a severe allergy as well as the impact it has on the professional development of teachers emerged. Three pre-service teachers with first-hand experience of anaphylaxis participated in a series of in-depth interviews over the course of five months. Guided by the hermeneutic approach to phenomenological research outlined by Max van Manen as well as the philosophical writings of Bernd Jager on the social experiences of eating, several essential themes surfaced. The lived experience of anaphylaxis can thus be understood through two actions: ‘The Inhale’ which is associated with perceived barriers of anaphylaxis and ‘The Exhale’ which is a sense of relief one experiences when one is managing an anaphylactic allergy. The three most significant contexts where these actions notably hindered or empowered pre-service teachers were: ‘The Habi(table) Environment’, the concept of safe spaces for those with anaphylactic allergies, ‘The Confron(table) Environment’, represented by spaces beyond a safe environment where there is a need to confront the allergy, and ‘The Respec(table) Environment’ which is an inter-subjective space between those with allergies and those without who are able to negotiate their needs with one another, allowing for the creation of respectable community. These themes, comprised of two actions and three contexts, thus serve to offer a sense of what it is like to live with and manage anaphylaxis. They also sensitize educators toward developing thoughtful, pedagogical responses to the increasing rates of anaphylaxis in the classroom.
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Nassiri, Maria. "Herz-Kreislauf-Medikamente als Kofaktoren der Anaphylaxie." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2015. http://dx.doi.org/10.18452/17188.
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Die Anaphylaxie, eine potentiell lebensbedrohliche Reaktion, kann durch Kofaktoren beeinflusst werden. ACE-Inhibitoren, ß-Blocker und Acetylsalicylsäure (ASS) werden häufig in der Therapie von Herz-Kreislauferkrankungen eingesetzt. In der vorliegenden Arbeit wurde überprüft, ob diese anaphylaktische Reaktionen begünstigen. Das Modell der passiv systemischen Anaphylaxie (PSA) wurde speziell angepasst, um die Behandlung einer Herz-Kreislauf-Therapie nachzubilden. Die orale Gabe von Metoprolol oder Ramipril verstärkte die Anaphylaxie geringfügig. Die Kombination der Medikamente steigerte die Anaphylaxie deutlich, was im Modell der passiv kutanen Anaphylaxie (PCA) bestätigt werden konnte. Gleichzeitig waren Mastzellmediatoren im Serum der Tiere erhöht. Die Inkubation muriner Mastzellen (MZ) mit den Medikamenten, steigerte die FcεRI-vermittelten Histaminfreisetzung in vitro. ASS-Vorbehandlung der Mäuse verstärkte die Ausprägung der PSA und der PCA, was mit einer Steigerung von MZ-Mediatoren im Serum assoziiert war. Die FcεRI-induzierte Histaminfreisetzung muriner MZ wurde hingegen nach ASS-Inkubation gehemmt, was auf einen indirekten Mechanismus hinweist. Die Reduktion der Prostaglandine (PG) durch ASS ist mit einer gesteigerten Leukotriensynthese verbunden. Der Leukotrienantagonist Montelukast konnte die, durch ASS verstärkte, PSA nicht mildern, was zeigt, dass dieser Effekt unabhängig von Leukotrienen ist. PGE2 kann die MZ-Degranulation über EP1-EP4-Rezeptoren modulieren. Tatsächlich schwächten EP3- und EP4-Rezeptoragonisten die durch ASS gesteigerte Anaphylaxie ab. PGE2 nimmt somit eine wichtige Rolle in der pro-anaphylaktischen Wirkung von ASS ein. Zusammenfassend wurde erstmals gezeigt, dass Metoprolol und Ramipril die Anaphylaxie über eine Steigerung der MZ-Reaktivität verstärken. ASS hingegen erhöht anaphylaktische Reaktionen über einen indirekt steigernden Effekt auf die MZ. PGE2 ist zumindest teilweise an der pro-anaphylaktischen Wirkung von ASS beteiligt.Cofactors contribute to the severity of anaphylaxis, a potential life-threatening hypersensitivity reaction. ACE-inhibitors, ß-blockers and acetylsalicylic acid (asa) are frequently used drugs in cardiovascular therapy. Whether they affect systemic anaphylactic reactions has been addressed within this thesis. To this aim, the passive systemic anaphylaxis model (PSA) was employed here and specially designed to mimic a long term treatment in cardiovascular therapy. The data demonstrate that oral treatment of mice with ramipril or metoprolol alone slightly aggravated anaphylaxis. However, the combination clearly potentiated anaphylactic reactions, which was also confirmed in the passive cutaneous anaphylaxis model (PCA). In line with this, elevated amounts of mast cell (MC) mediators were detected in mice sera upon combined drug treatment. In vitro, FcεRI-mediated histamine release of murine MCs was likewise enhanced by the respective drugs. Pre-treatment of mice with asa aggravated the symptoms of PSA and PCA; simultaneously MC-mediators in sera were elevated. In contrast, FcεRI-mediated histamine release of MCs was reduced by asa in vitro, pointing to an indirect mechanism. Asa reduces prostaglandins (PGs) and increases leukotriene synthesis. The leukotriene antagonist montelukast failed to attenuate PSA, aggravated by asa, suggesting that the pro-anaphylactic effect of asa might be independent of leukotrienes. PGE2 can modulate MC degranulation via EP1-EP4 receptor. Indeed, EP3 and EP4 receptor agonists alleviated anaphylaxis enhanced by asa. Therefore PGE2 might play an important role in the pro-anaphylactic effect of asa. In conclusion, the data demonstrate for the first time that metoprolol and ramipril exacerbate anaphylactic symptoms by a direct increase in MC reactivity. In contrast, asa aggravates anaphylactic reactions by priming MCs through an indirect mechanism. PGE2 is at least partly involved in this process.
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Sharma, Sribava. "Deletion of ΔdblGata Motif Leads to Increased Predisposition and Severity of IgE-mediated Food-induced Anaphylaxis Response." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535701847469787.
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Palosuo, Kati. "IgE-mediated allergy to dietary gliadin studies on wheat-dependent, exercise-induced anaphylaxis and childhood wheat allergy." Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/palosuo/.
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Yamani, Amnah. "Dysregulation of Vascular Endothelial Function Modulates Severity of IgE-mediated Anaphylactic Reactions." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1490350649626552.
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Wittenberg, Marcel [Verfasser]. "Serum levels of 9α,11β-PGF2 and apolipoprotein A1 achieve high predictive power as biomarkers of anaphylaxis / Marcel Wittenberg." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2018. http://d-nb.info/1170814115/34.
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Falanga, Yves. "Role of Fyn and Lyn in IgG-mediate immune responses." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/2874.
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Anaphylaxis is a rapid, life-threatening hypersensitivity reaction. Until recently, it was mainly attributed to histamine released by mast cells activated by allergen crosslinking (XL) of FcεRI-bound allergen-specific IgE. However, recent reports established that anaphylaxis could also be triggered by basophil, macrophage and neutrophil secretion of platelet activating factor subsequent to FcγR stimulation by IgG/Ag complexes. I have investigated the contribution of Fyn and Lyn tyrosine kinases to FcγRIIb and FcγRIII signaling in the context of IgG-mediated passive systemic anaphylaxis (PSA). I found that mast cell IgG XL induced Fyn, Lyn, Akt, Erk, p38 and JNK phosphorylation. Additionally, IgG XL of mast cells, basophils and macrophages resulted in Fyn- and Lyn-regulated mediator release in vitro. FcγR–mediated activation was enhanced in Lyn-deficient (KO) cells, but decreased in Fyn KO cells, compared to wild type cells. More importantly, Lyn KO mice displayed significantly exacerbated PSA features while no change was observed for Fyn KO mice, compared to wild type littermates. Intriguingly, this work establishes that mast cells account for the majority of serum histamine in IgG-induced PSA. Taken together, these findings establish pivotal roles for Fyn and Lyn in the regulation of PSA and highlight their unsuspected functions in IgG-mediated pathologies.
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Elkovich, Andrea J. "Mast Cells In Kainate Receptor Knockout Mice." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3944.
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Kainate receptor knockout mice have unique differences within their immune system. They exhibit an attenuated TH2 branch, while maintaining a robust TH1 response. Specifically, blocking the formation of functional kainate receptors affects mast cells and their related pathologies. While they seem to develop and activate normally in vivo and in vitro, KAR KO mast cells release more inflammatory mediators upon degranulation. These mice experience severe anaphylactic shock due to two compounding abnormalities. First, KAR KO mast cells release significantly more histamine in vivo upon IgE-mediated activation. Second, the animals over-respond to exogenous histamine with drastic temperature drops compared to WT. This report shows that the kainate receptor plays an important role in mast cell-mediated immune responses.
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Hua, Tonghuan. "Food allergy management in Early Childhood Education and Care (ECEC) Services: Are services aware of training guidelines for food allergy management?" Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2018. https://ro.ecu.edu.au/theses/2141.
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Background: Childhood food allergies (FA) are increasing in Australia. Although death from anaphylaxis caused by FA is rare, food-induced anaphylaxis could be fatal. It is unclear if staff in Early Childhood Education and Care (ECEC) are well prepared to manage food-induced anaphylaxis. This cross-sectional study utilised an online survey to assess the preparedness of ECEC staff nationally to manage FA.
Method: A survey addressing training, knowledge, skills and staff confidence to manage FA and anaphylaxis was emailed to 5956 ECEC centres nationally (excluding WA). Four hundred and ninety-four surveys were completed. Demographics were used to determine differences between State/Territory and socioeconomic status of the centres. Data was analysed using descriptive statistics and Chi-squared Test.
Results: A high proportion (76.7%) of ECEC services had children with a medically confirmed FA. A small percent (9.5%) of ECEC services did not require staff to undertake anaphylaxis training, which was non-compliant with current legislation. Staff confidence in FA and anaphylaxis management was high regardless of whether they had undertaken training, which indicated perception of confidence is not reflective of staff skill set to manage FA and anaphylaxis within services. Most (93.9%) ECEC services had a FA policy requiring Action Plans be provided. Over one third (37%) ECEC services stored adrenaline autoinjectors (AAI) in a locked location (not recommended). Approximately half (51.4%) of ECEC services reported having an AAI training device. NSW and Queensland had a significantly lower proportion of services with AAI training devices than Victoria (p-value < 0.001). Victoria reported the highest level of anaphylaxis management training (p-value < 0.05). Victorian services were also significantly less likely to store their AAI devices in a locked location compared to NSW and QLD (p-value < 0.001). There was no significant difference in staff training, knowledge, skills and confidence based on socio-economic status (p-value > 0.05).
Conclusion: ECEC staff self-reported a high level of training, knowledge, skills and confidence in FA and anaphylaxis management. However, this study revealed gaps in staff knowledge and skills, especially in how to correctly store and administer an AAI device. This study also identified a lack of awareness about the online FA and anaphylaxis training currently available. Better promotion of existing approved online training resources would increase the engagement of ECEC staff in anaphylaxis training
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Pointreau, Yoann. "Etude des sources de variabilité de l'efficacité et des effets indésirables du cetuximab chez les patients traités pour un carcinome épidermoïde de la tête et du cou." Thesis, Tours, 2015. http://www.theses.fr/2015TOUR3311/document.
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Le cetuximab (CTX) est un anticorps monoclonal anti-EGFR indiqué dans les cancers ORL dont les modalités de prescription pourraient être améliorées. Après chimiothérapie d’induction (étude Tremplin), en comparaison au cisplatine, il était moins toxique mais sans améliorer la préservation laryngée. À la première injection, le CTX peut déclencher un choc anaphylactique lié à la préexistence d’IgE anti-αGal. Des tests prédictifs détectant ces IgE ont été développés et réalisés chez 41 patients avec une sensibilité et une valeur prédictive négative de 100%. La relation entre concentrations sériques et efficacité/toxicité a été étudiée chez 34 patients. La pharmacocinétique a été décrite à l’aide d’un modèle combinant des mécanismes d’élimination non saturable (CL) et saturable (k0). La clairance globale du CTX, reflet de l’exposition des patients, était reliée aux survies sans progression et globale (SG). Le grade de radiodermite était associé à la SG. Une simulation pharmacocinétique suggère, qu’en comparaison à l’injection standard de CTX, une injection toutes les trois semaines entrainera des AUC proches mais des concentrations résiduelles différentesCetuximab (CTX) is an anti-EGFR monoclonal antibody approved in head and neck cancer, which prescription modalities may be improved. After induction chemotherapy (Tremplin study), compared to cisplatin, CTX was less toxic but did not improve larynx preservation. During first infusion, CTX can induce an anaphylaxis reaction due to the presence of preexisting anti-αGal IgE. Predictive assays detecting these IgE were developed and tested in 41 patients, with sensitivity and negative predictive values of 100%. Relationship between serum concentrations and efficacy/toxicity was studied in 34 patients. CTX pharmacokinetics was described using a model combining non-saturable (CL) and saturable (k0) eliminations. Global clearance, which reflects patient exposure, was related to progression free and overall (OS) survivals. Severe radiation dermatitis was also associated with OS. A pharmacokinetic simulation suggests that, in comparison to standard CTX infusion, an infusion every three weeks will lead to similar AUC but to different residual concentrations
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Guth, Lars. "Barn och ungdomars upplevelser av att leva med risk för anafylaxi." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-334247.
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Bakgrund: Anafylaxi är en akut, svår, oftast snabbt insättandes systemisk överkänslighetsreaktion från flera organsystem och är potentiellt livshotande. Det ses en ökad förekomst av anafylaxi i samhället över tid sedan 90-talet. Syfte: Att undersöka barn och ungdomars (0–19 år) upplevelser av att leva med risk för anafylaxi. Metod: En litteraturstudie med tio kvalitativa artiklar. 170 barn och ungdomar deltog. Sökningar gjordes i PubMed, CINAHL och PsycINFO. En sekundärsökning utfördes. Resultatet presenterades med en syntes. Omvårdnadsteori: Roys adaptionsmodell. Resultat: Upplevelser kategoriserades i Känslomässig påverkan och Begränsningar i vardagen. Faktorer delades in i Mitt hem – Min familj – Min säkerhet, Miljön, Adrenalinpennan, Erfarenhet av anafylaxi, Innehållsförteckningar – ”kan innehålla spår av…”, Okunskap och Källor till stöd. Strategier delades in i Att hela tiden vara på sin vakt – värdera risker, Normalisering och Erfarenhet leder till kunskap, vilket resulterar i självsäkerhet – En genomresa. Slutsats: De allergiska barnen visade en mångfacetterad bild av att leva med risk för anafylaxi, med effekter på livskvalitet och välbefinnande initialt i livet som följd. Problematiken visades paradoxalt vara en övergående börda för de flesta: de allergiska barnen genomgick en första tid av adaption, till följd av vilken allergin blev en del av livet under tonåren. Denna litteraturstudie ger djupare insikt i allergiska barn och ungdomarnas upplevelser, samtidigt som den ger underlag till idéer för framtida forskning, i syfte att ta reda på hur samhället och sjukvården på bästa sätt skall utvecklas, för att främja adaption till att leva med risk för anafylaxi.
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Lima, Karine De Amicis. "Identificação, expressão, purificação e caracterização de novos alérgenos do veneno da vespa Polybia paulista." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-14122017-112139/.
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As hipersensibilidades do tipo I são caracterizadas por um grupo heterogêneo de manifestações clínicas que atingem mais de 30% da população mundial. Novas reatividades a alérgenos regionais brasileiros têm sido descritas e muitas fontes ainda não são totalmente conhecidas. Dentre os alérgenos mais prevalentes estão os venenos de insetos. A vespa regional Polybia paulista (Hymenoptera vespidae) é endêmica no sudeste do Brasil e é responsável por acidentes graves, causando reações alérgicas que podem levar ao choque anafilático. Alguns componentes dos venenos de vespas de diferentes espécies apresentam mimetismo molecular ou biológico, podendo gerar reação imunológica cruzada, mas muitas vezes não são os responsáveis pelo desencadeamento da resposta alérgica. Isto ocasiona falha no diagnóstico e consequentemente no tratamento indicado, a imunoterapia alérgeno-específica. Diante desses fatos e do grande número de pacientes que procuram o Serviço de Imunologia Clínica e Alergia do Hospital das Clínicas de São Paulo (HCFMUSP) com manifestações clínicas de alergias a ferroadas de insetos, foi desenvolvida uma sistemática de investigação clínica e laboratorial, com ênfase na abordagem proteômica, para identificar e caracterizar físico-química e imunologicamente novos alérgenos do veneno da vespa Polybia paulista e estudar potenciais reatividades cruzadas com alérgenos já conhecidos. Vinte e um pacientes com história de anafilaxia a venenos de vespa foram selecionados para participar do estudo. Foram realizados testes cutâneos e in vitro com veneno de Polistes spp. disponível comercialmente e com o veneno da Polybia paulista, produzido seguindo o protocolo padronizado anteriormente. Os resultados mostraram que a maioria dos pacientes apresentam IgE específica para os dois venenos com maior reatividade ao veneno de Polybia e que o padrão de proteínas reconhecidas entre os dois venenos é diferente, evidenciando a necessidade de veneno de Polybia paulista na prática clínica nas regiões cuja vespa está presente. Foram identificadas mais de 2000 proteínas no extrato total do veneno de Polybia paulista e algumas proteínas alergênicas ainda não descritas. Dentre elas foi identificada uma nova isoforma ao antígeno 5 da vespa Polybia scutellaris relatada como hipoalergênica. A molécula foi produzida na forma recombinante com conformação adequada, pela primeira vez em E. coli. O alérgeno, registrado na IUIS como Poly p 5, foi reconhecido por IgEs no soro dos pacientes testados e apresenta reatividade cruzada com outros antígenos 5 homólogos. Testes de desgranulação de basófilos em linhagem celular de ratos mostraram que o Poly p 5 induziu pouca desgranulação, indicando seu potencial hipoalergênicoType I hypersensitivity is characterized by heterogeneous clinical manifestations and specialists estimate that today around 30% of the general population suffers from an allergic disease. New allergens are being reported and some sources are not yet identified. Insect venoms are amongst the most prevalent allergen sources. The social wasp Polybia paulista (Hymenoptera vespidae) is endemic in the southeastern of Brazil and is responsible for serious accidents due to their venomous stings, causing allergic reactions that can lead to anaphylactic shock. Several components presenting molecular or biological mimicry can be found in different species of wasps and lead to a cross-immunological reaction but they are not always responsible for the allergic manifestations. Therefore, diagnostic and consequently immunotherapy is unsuccessful, since specific allergen identification is crucial. Considering the high number of patients attended at the \"Serviço de Imunologia Clínica e Alergia do Hospital das Clínicas de São Paulo\" with clinical manifestations of allergies not yet determined or barely studied, an approach involving a systematic clinical, laboratorial and investigative practice through a proteomic analysis was created to identify and characterize new allergens of Polybia paulista venom. Twenty-one patients with clinical history of anaphylaxis to Hymenoptera venoms were selected for this work. Cutaneous and in vitro tests were performed using Polistes venom commercially available as well as Polybia paulista venom, produced following a published protocol. The results shows that the majority of the patients has specific IgE for both venoms with biggest reactivity to Polybia paulista venom and the protein profile recognized in these venoms is different. More than 2000 proteins were identified in the whole venom extract of Polybia paulista and some of the allergenic proteins are not yet described in this venom. Among them, a new isoform that is similar to antigen 5 from Polybia scutellaris, already known as hypoallergenic. The molecule was produced as a recombinant properly folded for the first time in E. coli. The allergen, registered at IUIS as Poly p 5, was recognized by IgEs in the sera of 50% of the patients tested and has cross-reactivity with other homologs of antigen 5. Basophil degranulation tests in rat lineage cells showed that Poly p 5 induced little degranulation, indicating the hypoallergenic potential of this molecule
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Rachid, Ousama. "Evaluation of the effects of non-medicinal ingredients on the in vitro characteristics and in vivo bioavailability of a sublingual tablet formulation of epinephrine." Elsevier: J Allergy Clin Immunol, 2010. http://hdl.handle.net/1993/18315.
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Objectives: To review, develop, and validate appropriate methods for quality control testing of sublingual (SL) tablets; to formulate and characterize new generations of SL tablets of epinephrine (E) for the potential first-aid treatment of anaphylaxis; and to evaluate the effects of non-medicinal ingredients (NMIs) on the in vitro characteristics and in vivo bioavailability of the formulated tablets. Methods: A custom-made apparatus and a novel method that simulates SL conditions were evaluated for dissolution testing of SL tablets. An electronic tongue (e-Tongue) was used to assess the degree of E bitterness and to demonstrate the masking effects of sweetening and/or flavoring agents. The effect of several NMIs in various properties on the in vitro characteristics of new generations of E SL tablets was evaluated. Formulations with the best in vitro characteristics, containing E 30 mg and 40 mg, were evaluated in vivo using our validated rabbit model and compared with placebo SL tablets (negative control) and E 0.3 mg intramuscular (IM) injection (positive control). Results: The novel in vitro dissolution testing resulted in accurate and reproducible data and was capable of detecting the effect of minor changes in formulations. Using the e-Tongue, E bitartrate had an extremely bitter taste which was masked to various degrees by the addition of aspartame, acesulfame potassium, and citric acid alone or in combination. Citric acid alone masked the bitter taste by >80%. The evaluation of NMIs revealed that the best formulation contained specific proportions of mannitol and coarse and fine grades of microcrystalline cellulose. Appropriate comparative testing resulted in the selection of a taste-masked E SL formulation with optimum in vitro characteristics. This formulation containing E 40 mg resulted in similar bioavailability to E 0.3 mg IM. This formulation containing E 30 mg had higher bioavailability than placebo, but lower bioavailability than E 40 mg tablets. Conclusions: Grades and proportions of NMIs carefully selected using appropriate in vitro testing resulted in successful formulations. The results of these in vitro tests enabled the development of the optimum E SL tablet formulation which was bioequivalent to the EpiPen. These tablets are potentially suitable for Phase 1 studies in humans and might transform the first-aid treatment of anaphylaxis in community settings.
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Aresh, Bejan. "Functional Aspects of Peripheral and Spinal Cord Neurons Involved in Itch and Pain." Doctoral thesis, Uppsala universitet, Genetisk utvecklingsbiologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-284070.
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We have investigated the role of the metabotropic glutamate receptor 7 (mGluR7) and the gastrin releasing peptide receptor (Grpr) population that are involved at different levels of itch transmission. We found that mGuR7 deficient mice displayed an anaphylaxis-like behavior when provoked with histamine. Analysis of blood revealed elevated plasma levels of histamine and mouse mast cell protease-1 (mMCP1), two indicators of anaphylaxis, in mGluR7 deficient mice compared with control mice. Inhibition of the neurokinin 1 receptor, by preventing binding of the corresponding ligand substance P (SP), prior to provocation with histamine prevented the development of anaphylaxis in mGluR7 deficient animals. However, blocking GRPR (gastrin releasing peptide receptor) only resulted in decreased itch levels in mGluR7 deficient mice but did not prevent the systemic anaphylaxis-like behavior. Our findings indicate that mGluR7 normally functions as a brake on histaminergic itch that is mediated through GRPR as well as anaphylaxis through Substance P. Grpr has previously been shown to mediate both histaminergic and non-histaminergic itch but little is known about the GRPR neuronal population. We used a BAC cloning strategy to construct a Grpr-Cre line, which we crossed with the reporter lines tdTomato and Viaat-egfp as well as with Vglut2-lox. We could conclude that Grpr-Cre neurons are mainly excitatory interneurons located in lamina II-IV, that convey itch using VGLUT2-mediated glutamatergic transmission to the next, currently unknown, step in the labeled line of chemical itch. To eventually deduce the function of the endogenous opioids dynorphin and enkephalin, which are hypothesized to be involved in gating pain and itch in the spinal cord, we constructed two Cre lines using BAC cloning that targeted the precursor proteins preprodynorphin and preproenkephalin, respectively. Preprodynorphin-Cre neurons were mainly located in lamina II-IV and overlapped to 47% with Vglut2 mRNA, while the co-expression with the inhibitory markers Viaat-egfp and PAX2 was 13% and 28% respectively in the spinal cord. Preproenkephalin neurons were more localized to lamina III in the dorsal horn, furthermore single cell analysis showed that they overlapped to 94% with Vglut2 mRNA while 7% and 13% expressed Viaat-egfp and PAX2 respectively.
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Silva, Aldacilene Souza da. "Anticorpos anafiláticos induzidos por componentes de alto peso molecular de Ascaris suum: regulação da resposta primária e secundária por citocinas." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-19092018-110326/.
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Estudos anteriores mostraram um efeito supressivo do extrato de Ascaris suum (Asc) nas respostas humoral e celular a um antígeno heterólogo. O fracionamento deste extrato por gel filtração possibilitou a identificação de picos distintos, constituídos de proteínas de alto peso molecular (PI) e baixo peso molecular (Plll), sendo o efeito supressivo de Asc restrito aos componentes de PI. Com relação à produção de anticorpos contra estes componentes, verificou-se que PI é capaz de induzir preferencialmente a síntese de lgG1 não-anafilática e baixos títulos de lgE e de lgG1 anafilática. Considerando que estes resultados foram obtidos no 8º día após a imunização dos animais, propusemos-nos a estudar a indução de anticorpos anafiláticos por PI em fases mais tardias da resposta imune e sua regulação por citocinas. Os nossos resultados mostraram que a indução da lgG1 anafilática anti-PI é mais tardia e regulada parcialmente por IL-4, tanto na resposta primária como secundária. A produção de lgE é totalmente dependente de IL-4. Devido à heterogeneidade presente em nossos animais, pudemos constatar apenas uma tendência de regulação negativa de IL-12 e IFN -γ sobre a produção dos anticorpos lgG1 anafiláticos e lgE, no início da resposta primária. Entretanto, nossos resultados mostraram um efeito importante da IL-10, em conjunto com IFN-γ, na inibição da síntese de anticorpos anafiláticos anti-PI, tanto na resposta primária como secundária. Com relação à lgG1 não-anafilática anti-PI, sua indução parece depender de IFN-γ apenas na resposta primária.Previous studies have shown a suppressive effect of Ascaris suum extract (Asc) on humoral and cell-mediated immune responses to a non-related antigen. After fractionation of this extract by gel filtration, two peaks were identified according to their molecular weights, and the suppressive effect was associated with proteins of high molecular weight (PI). PI induces high levels of non-anaphylactic lgG1 and low levels of lgE and anaphylactic lgG1. Since these results were obtained 8 days after immunization, the aim of this work was to follow the production of anti-PI anaphylactic antibodies during the primary as well as the secondary antibody response. We algo studied the modulation of the anaphylactic antibody production by cytokines. Pl-specific anaphylactic lgG1 was produced lately in the primary response and was partially dependent on IL-4, including the secondary response. lgE was not produced in the absence of IL-4 at any time. IL-12 and IFN- γ exerted a slight negative effect on Pl-specific anaphylactic lgG1 and lgE antibody production in the beginning of the primary response. In contrast, IL-10 together with IFN- γ had a profound inhibitory efíect on the synthesis of these antibodies in the primary and secondary responde. The production of Pl-specific non-anaphylactic lgG1 antibodies depended upon IFN- γ only in the prímary response.
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Javed, Najma H. "Interaction of the immune system and enteric nervous system in guinea pig distal colon : mediators causing release of acetylcholine and chloride secretion during intestinal anaphylaxis /." The Ohio State University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=osu148777866328618.
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Soliani, Fernanda Miriane Bruni. "Anafilaxia induzida em camundongos pelo veneno do peixe Thalassophryne nattereri." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-01082012-085026/.
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As alergias podem ser desencadeadas por substancias químicas, medicamentos, proteínas de origem vegetal e animal como, por exemplo, ácaros, alimentos, fungos e venenos. Reações alérgicas desenvolvidas em resposta a venenos de animais marinhos vêm sendo pouco estudadas. Este é o primeiro estudo que descreve a indução de reação anafilática em camundongos pelo veneno de um peixe brasileiro, acompanhado da caracterização detalhada dos mediadores solúveis e celulares envolvidos no processo. Nossos resultados mostram que o veneno do peixe T. nattereri possui proteínas alergênicas capazes de desencadear um processo alérgico, caracterizado por anafilaxia mediada por IgE e IgG1 e inflamação eosinofílica de fase tardia dependente de citocinas Th2. Ainda demonstramos a regulação da resposta pela positiva pela citocina IL-4 e participação da IL-12 e IFN-g na resposta.Allergies are a significant and widespread public health problem. Anaphylaxis reactions are inducing by foods, medications and venoms and are IgE mediated. In mice, allergy can be caused also by IgG1. The results presented here describe for the first time anaphylaxis induced by Brazilian fish venom, accompanied by detailed characterization of soluble and cellular mediators involved in the process. Together our results demonstrated that the venom of T. natereri has allergenic proteins that can trigger allergic process, a phenomenon IgE-IgG1 dependent, IL-4 mediated and regulated by IFN-g. Furthermore, we observed a positive participation of the cytokines IL-12 and IFN-g in the exacerbation of the late phase reaction.
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Silva, Sandriana dos Ramos. "Estudo comparativo da região Fc de anticorpos IgG1 murinos anafiláticos e não-anafiláticos." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-19052010-134913/.
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Está estabelecido que o processo de glicosilação é essencial para a conformação estrutural e função efetora dos anticorpos. Entretanto, não está completamente claro como diferenças nos carboidratos ligados aos anticorpos podem interferir na sua atividade biológica. Foi previamente descrito que anticorpos IgG1 murinos podem ser divididos em anafiláticos ou não-anafiláticos, de acordo com a sua capacidade de induzir in vivo reação de anafilaxia. Somado a isso, foi verificado que a cadeia de oligossacarídeos N-ligada à molécula de IgG1 é fundamental para a manutenção da sua função efetora. O objetivo do presente trabalho é estudar diferenças estruturais entre os subtipos de IgG murinos que poderiam determinar a sua atividade biológica. O seqüenciamento dos nucleotídeos que codificam os domínios CH2 e CH3 dos dois subtipos de IgG1 permitiu constatar homologia de 100% dessas regiões nas duas moléculas estudadas. Entretanto, ao analisar o padrão de carboidratos N-ligados aos anticorpos IgG1 foi observado maior conteúdo de ácido siálico e fucose na cadeia N-ligada ao anticorpo anafilático em relação à do não-anafilático. Contudo, a remoção de resíduos de ácido siálico por tratamento enzimático do anticorpo IgG1 anafilático resultou na perda da capacidade desta molécula de induzir desgranulação celular in vitro e reação anafilática in vivo, semelhante ao anticorpo IgG1 deglicosilado. Em contraste, a remoção de fucose não afetou a sua função anafilática. A análise por PCR em tempo real da expressão dos genes das enzimas envolvidas no processo de glicosilação das proteínas revelou menor expressão gênica de algumas glicosidases, principalmente as sialiltransferases, no hibridoma e linfócitos B secretores do subtipo IgG1 não-anafilático em relação ao obtido no hibridoma e linfócitos B que secretam a IgG1 anafilática. Além disto, foi observada menor atividade enzimática das sialiltransferases obtidas do hibridoma produtor da IgG1 não-anafilática em relação à do hibridoma que produz a IgG1 anafilática. Em conjunto, estes resultados comprovam que a capacidade de anticorpos IgG1 murinos de induzir anafilaxia é diretamente dependente do conteúdo de ácido siálico presente na cadeia de oligossacarídeos ligada à região Fc do anticorpo, além disso sugerem fortemente que essa maior sialilação observada no tipo anafilático seja resultante da maior expressão gênica destas enzimas e assim da sua atividade enzimática no momento da síntese dos anticorpos.It is well established that the glycosylation process is essential for the structural conformation and effector function of the antibodies. However, it is quite clear how differences in the carbohydrates attached to the antibodies may interfere with their biological activities. It was previously reported that murine IgG1 antibodies can be divided into anaphylactic or nonanaphylactic according to their ability to induce anaphylaxis. Furthermore, it was demonstrated that the oligosaccharide chain N-linked to the IgG1 is essential for its conformation and biological activity. The objective of this work is to study structural differences between these subtypes of murine IgG1 that could determine their biological activity. The sequencing of the nucleotides encoding the CH2 and CH3 domains of these two subtypes of IgG1 showed 100% of homology in the Fc regions of these molecules. In contrast, the analysis of the carbohydrates N-linked to the IgG1 antibodies demonstrated higher sialic acid and fucose contents in the chain attached to the anaphylactic antibody than in the nonanaphylactic IgG1. However, the removal of sialic acid residues by enzymatic treatment of anaphylactic IgG1 antibody resulted in the abrogation of its ability to induce mast cells degranulation in vitro and anaphylactic reaction in vivo as observed to deglycosylated IgG1 antibody. On the other hand, the removal of fucose did not change the anaphylactic activity. The analysis by real time PCR of the gene expression of enzymes that are involved in the protein glycosylation showed lower gene expression of some glycosyltransferases, mainly sialyltransferases, in the hybridoma and B lymphocytes that produce the non-anaphylactic IgG1 compared to those verified in the hybridoma and B cells producer of the anaphylactic IgG1. Furthermore, it was verified lower enzymatic activity of sialyltransferases purified from the hybridoma producer of the non-anaphylactic IgG1 in relation to the hybridoma producer of the anaphylactic antibody. Together, these results prove that the ability of murine IgG1 to induce anaphylaxis is directly dependent of the sialic acid content in the carbohydrate core attached to the antibody Fc region. It is also strongly suggested that this higher sialylation observed in the anaphylactic IgG1 may be resultant of the higher gene expression and enzymatic activity of some sialyltransferases during the antibody synthesis.
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Blad, Anneli, Linda Jensen, and Caroline Palmé. "Föräldrars erfarenheter av att leva med barn med födoämnesallergi med särskilt fokus på anafylaxi/Parents experiences of living with children who has food allergy with special focus on anaphylaxis." Thesis, Kristianstad University College, Department of Health Sciences, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:hkr:diva-3992.
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Background: When a child is diagnosed with food allergy with risk of anaphylaxis, it affects the whole family. The child must learn to live with a chronicle disease and learn the importance of avoiding the specific allergens that may cause a life-threatening condition. The parents must adapt to a way of life with limitations in the everyday life as well as a constant concern for the child. They must learn to handle an auto-injector and to recognize symptoms of a coming anaphylaxis. Aim: The aim of this study was to describe parent’s experiences of living with children who has foodallergy with special focus on anaphylaxis. Method: This was a literature review, based on twelve scientific articles, both qualitative and quantitative. The results from the articles were analysed with content analysis. Results: The analysis resulted in four central categories: experience of information and knowledge, consequences of inadequate information, experience of limitations and anxiety in the family’s daily life and strategies for handling of anxiety in the daily life. Conclusion: Parents to children with allergy with risk of anaphylaxis need information, knowledge and support about the child’s care in order to handle restrictions and anxiety in the daily life.
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Archibald, Timothy, Stacy Brown, and Alexei Gonzalez-Estrada. "Refrigerated Stability of Diluted Succinylcholine, Pancuronium, and Atracurium." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/88.
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Refrigerated Stability of Diluted Succinylcholine, Pancuronium, and Atracurium.
T. Archibald1, S. Brown1, A. Gonzalez-Estrada2
1College of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN2Quillen College of Medicine, Allergy and Clinical Immunology, East Tennessee State University, Johnson City, TN
The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely succinylcholine, pancuronium, and atracurium, for skin prick/intradermal testing.
Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x as sensitivity of the assay allowed. Each drug was prepared with an n = 5 for each dilution, using a different newly opened product for each series. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days (day 0, 1, 2, 4, 7, and 14), one milliliter aliquots of each dilution were removed, filtered, and analyzed against freshly prepared set of reference dilutions.
The results are expressed as beyond use date (BUD), defined as recovery of drug versus the reference (90-110%). Based on the LC-MS/MS data, the BUD for succinylcholine diluted by 10x and 100x is 48 and 24 hours, respectively. The1000x dilution is also stable for 24 hours.Higher dilutions of succinylcholine (10,000x to100,000x) should be used immediately following preparation (within less than 24 hours), as the potency of these dilutions had decreased below 90% at the 24 hr sampling. .Pancuronium diluted by 10x and 100x, had a BUD of 48 hours, and the1,000x dilution was stable for 24 hours.As with the succinylcholine, the 10,000x and 100,000x dilutions expressed potency of <90% at 24 hours. .Atracurium diluted to 10x had a BUD of 96 hours, the100x dilution is stable for 24 hours yet higher dilutions (1,000x to 10,000x) do not persist beyond 24 hours. . The 100,000x dilution of atracurium was unknown, given than the signal intensity was too weak to monitor by our LC-MS/MS method.
With increasing dilution factors, the stability of these drugs in saline decreases, associated with an increasing deviation between samples and freshly prepared references. The most stable dilutions for each of the drugs tested were 10x and 100x. Stability of these drugs is likely compromised by hydrolysis of the ester bonds in the drug molecules.
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Nohra, Dunya. "Optimisation des tests de provocation en allergologie médicamenteuse." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS453.
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L’hypersensibilité incluant les allergies médicamenteuses est un des multiples effets secondaires médicamenteux. On note à la fois un sous-diagnostic de ces hypersensibilités, par non-déclaration des cas les plus bénins, et un sur-diagnostic, par utilisation systématique du terme « allergie » devant des symptômes survenant au cours d’un traitement. Un faux diagnostic d’allergie fondé exclusivement sur l’histoire clinique peut limiter les indications thérapeutiques chez les patients et conduire à une perte de chance par l’utilisation de médicaments moins efficaces, plus dangereux ou plus coûteux. De plus, une allergie à un médicament peut laisser penser que le patient est allergique à tous les médicaments de la même classe. Le test de provocation (TP) est considéré le « gold standard » pour identifier un médicament responsable d’une hypersensibilité médicamenteuse. Ce travail s’inscrit dans une démarche d’optimisation des TP basée sur les preuves, visant à la fois la satisfaction du patient et les coûts engendrés, tout en préservant la sécurité des tests. J’ai utilisé l’expérience de 20 ans recensée dans la base d’allergies médicamenteuses, DAHD (Drug Allergy and Hypersensitivity Database), j’ai exploité rétrospectivement les données cliniques, recensé les cas présents dans la base pour en extraire les TP positifs et j’ai réalisé une analyse de survie pour passer des protocoles de TP aux anti-inflammatoire non-stéroïdiens (AINS) d’une étape avec paliers purement empiriques, à un protocole basé sur des données (Article 1) en tenant compte des spécificités liées à ces médicaments (multitude de molécules impliquées, chacune avec un pouvoir hypersensibilisant clairement différent). Avec les conclusions obtenues pour ce premier travail, pour mon deuxième papier, j’ai repris des données brutes déjà existantes liées à l’expérience de l’équipe pour les hypersensibilités au paracétamol, et en suivant la même méthodologie, j’ai proposé des paliers optimaux raccourcis pour le TP au paracétamol (en surlignant la particularité de l’hypersensibilité aux AINS versus paracétamol) (Article 2) en appuyant sur les facteurs de risques pour un TP positifDrug hypersensitivity (DH) including drug allergies is one of the many side effects of medications. The knowledge on DH is both influenced by an under-diagnosis (the non-reporting of the mildest cases) and over-diagnosis, by systematic use of the term "allergy" to symptoms occurring during a course of treatment, whether they are actually evocative of DH or not. A false diagnosis of DH based solely on clinical history may limit the therapeutic indications in patients and lead to a loss of chance through the use of less effective, more dangerous or more expensive drugs. The drug provocation test (DPT) is considered to be the "gold standard" to identify a drug responsible for DH. This work uses an original methodology for the DH field and is part of an evidence-based approach to achieve the optimization of DPT, aimed to both increase patient satisfaction and diminish the costs incurred by the allergy work-up, while preserving the DPT’s safety. I used the 20-year experience in the DAHD, the Drug Allergy and Hypersensitivity Database of the Allergy Unit in Montpellier, France, to retrospectively assess the clinical data, identify cases and extract positive DPT to NSAIDs. I then performed on these positive DPT a survival analysis in order to pass protocols from a stage with purely empirical increments of doses, to data-driven protocols (Article 1) taking into account the specificities related to these drugs (e.g., multitude of molecules involved, each with a clearly different hypersensitive potential). With the conclusions obtained for this first work, for my second paper, I took over already existing raw data related to the team's experience with paracetamol HS, and following a similar methodology, I proposed optimized, shortened thresholds for paracetamol DPT (Article 2)
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Bellou, Abdelouahab. "L' anaphylaxie : approche clinique descriptive et approche expérimentale chez le rat Brown Norway sensibilisé à l'ovalbumine." Nancy 1, 2001. http://www.theses.fr/2001NAN11303.
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Paßmann, Benedikt [Verfasser]. "Validierung des Anaphylaxie-Registers / Benedikt Paßmann." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/1075493358/34.
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