Symptoms Of Anaphylactic Shock Research Articles

Effects of a standardized patient-based simulation in anaphylactic shock management for new graduate nurses

BackgroundPatients may be endangered if new graduate nurses cannot recognize and manage anaphylactic shock. Consequently, enhancing the new graduate nurses’ understanding of their roles and responsibilities during the rescue of a patient with anaphylactic shock is important. However, due to its inherent limitations, traditional classroom-based teaching makes it difficult to explore the potential of the students. Although popular simulation teaching has several notable advantages, it has not been proven to be effective in training inexperienced nurses on anaphylactic shock. We investigated the effect of a standardized patient-based simulation on the behaviors of new graduate nurses’ during anaphylactic shock rescue to identify an effective and safe method for contemporary nursing education.MethodsExcept for the ill or pregnant, all the new graduate nurses were included in the study as students to undergo a standardized patient-based simulation conducted in the clinical skills center of a general hospital. The simulation training was designed to teach students to recognize the signs and symptoms of anaphylactic shock, place the patient in the correct position, stop the ongoing intravenous infusion of the antibiotic which triggers the anaphylactic shock, restart an intravenous infusion on a new infusion apparatus, give 100% oxygen via a nasal cannula or mask, preserve airway patency, call the rapid response team, and correctly administer the medications prescribed by the clinicians. Before and after the training, the instructors evaluated each student’s skills and behaviors using a clinical competency evaluation list. After the training, all students completed the Chinese version of the Simulation Design Scale (SDS) to demonstrate their satisfaction with the program and then participated in semi-structured interviews with their instructors.ResultsAll 104 graduate nurses had a significant improvement on the 6 competencies of the clinical competency evaluation list after the simulation training (P < 0.001). The SDS scores revealed that the students were highly satisfied with all the aspects of the simulation training (the 20 satisfaction rates were all above 90.00%). During the semi-structured interviews, most of the new graduate nurses reported that simulation training in the management of anaphylactic shock was critical and would guide them in clinical practice.ConclusionSimulation training in anaphylactic shock is a potentially viable and effective method for teaching new graduate nurses to manage clinical incidents.

A new method to reduce allergenicity by improving the functional properties of soybean 7S protein through covalent modification with polyphenols

The 7S fraction contains several major allergens of soybean protein. Here, the effects of covalent modification by chlorogenic acid (CHA) and (−)-epigallo-catechin 3-gallate (EGCG) on the allergenicity and functional properties of soybean 7S protein were investigated. Conjugation with EGCG and CHA resulted in the formation of cross-linked protein polymers and changes to the structures of the protein, which might mask or destroy the epitopes on it. In vitro analysis revealed that modification by polyphenols noticeably reduced IgE binding activity and histamine release. In vivo analysis showed that modification led to milder anaphylactic shock symptoms and minor damage of the intestine in mice, with reducing IgG, IgE, IgG1, mMCP-1, and histamine levels. The allergic response was also suppressed by the repression of IFN-γ, IL-4, and IL-5 and the up-regulation of IL-10 and TGF-β in the conjugate groups. Furthermore, modification enhanced antioxidant, emulsion, foaming capacity, and foam stability of the protein.

The role of glucocorticoids in the treatment of acute anaphylactic reaction

Food allergy is a growing health problem, which is particularly common among the youngest children. Anaphylaxis, which is defined as a sudden-onset and potentially fatal response to an allergen, is an indication for urgent treatment. Although intramuscular epinephrine is the treatment of choice, all therapeutic algorithms also recommend glucocorticoids. They play an important role in reducing the risk of late allergic reaction, and, due to their non-genomic effects, are also increasingly often mentioned in the context of early response to shock. This effect is directly proportional to the dose of the drug, and a reduced duration of the symptoms of anaphylactic shock is achieved with the use of high doses of glucocorticoids. The paper presents a case of a 3-month-old girl with an anaphylactic reaction after consuming a modified milk preparation. After systemic administration of glucocorticoids, a satisfactory therapeutic effect was observed in the child.

COVID-19; VACCINE ADMINISTRATION AND THE ROLE OF NURSES/ MIDWIVES

The COVID-19 vaccine is finally available in the market and across the globe its public administration has started widely. Safe and effective administration of COVID-19 vaccine is the primary responsibility of nurses, midwives and other healthcare professionals1. Therefore, nurses and other professionals who are involved in administering vaccines must be knowledgeable, confident and competent. Nurses have main role in the administration of the COVID-19 vaccine therefore it is compulsory that nurses possess accurate knowledge and skills to administer vaccines2. Core competencies required of nurses include product knowledge, storage and handling, administration and documentation3.&#x0D; Before administering vaccine training is required. Depending on the product nurses must have knowledge of the eligibility requirements, vaccination schedule and history, contraindications, precautions and clinical considerations4. Moreover, it is important to understand recommended observation time and signs and symptoms of allergic reactions and anaphylactic shock (if any). Safe administration also requires that nurses must possess accurate knowledge of storage and handling of COVID-19 vaccine including inspecting, unpacking, accounting, and storing vaccines5. Depending on the product, nurses must demonstrate the knowledge of maintaining cold chain and any protocol in case of cold chain failure. Proper monitoring of temperature and recording it are vital for safe and effective administration of COVID-19 vaccine.&#x0D; Administration of vaccine is the key competency required of nurses that include infection prevention and control as well as mitigation measures. Identifying proper needle gauge and length is important in addition to best injection site based on route, age and health of the recipient6,7. Correct intramuscular injection technique is the cornerstone to prevent administration errors such as shoulder injury etc. Similarly, nurses should have the knowledge as per standard protocol of how to dispose vials, syringes, needles and other supplies8. Finally, proper documentation of vaccination is key in appropriate data systems. Evidence suggest that health care professionals including nurses and midwives are highly trusted when it comes to vaccine information therefore it is vital that nurses provide appropriate information including vaccination report card to vaccine recipient. Nurses should also be able to explain to the patient any adverse effect and what to do in such situations.&#x0D; For the safe and effective administration of vaccine, it is important that nurses must self-assess themselves in the above areas and where required must improve themselves before embarking on to administer COVID-19 vaccines to public. Facilities and vaccine centers must arrange training and refresher courses for nurses and support staff involved in administration of vaccines.

A multi-center assessment to compare residual allergenicity of partial hydrolyzed whey proteins in a murine model for cow’s milk allergy – Comparison to the single parameter guinea pig model

IntroductionThis 4-center study is part of a project to validate a food allergy murine model for safety testing of hydrolyzed infant formulas. AimThe aim of the current multi-center experiment was to evaluate the residual allergenicity of three partial hydrolyzed whey proteins (pWH) in a multiple-parameter cow’s milk allergy murine model and to compare to the classically used guinea pig model. Previous work showed differences in the magnitude of the allergic response to whey between centers. To get a first insight in the effect of housing on the robustness of the mouse model, microbiota composition of non-sensitized mice was analyzed and compared between centers. MethodsMice were sensitized intragastrically (i.g.) with whey, pWH or eWH using cholera toxin as an adjuvant. In mice, whey-IgE/IgG1, acute allergic symptoms were determined upon whey challenge. Guinea pigs were orally sensitized ad libitum via the drinking water (day 0–37) and challenged intravenously with whey on day 49. The microbial composition in fecal samples was determined in non-sensitized mice in all 4 research centers before and after conduct of the study. ResultsElevated levels of whey-IgG1 were detected in whey-sensitized mice in all centers. Except for pWH-A in center 4, we observed elevated levels of whey-IgE in whey-sensitized mice and mice sensitized with pWH-A, -B, -C. Center 2 was excluded from further analysis because of non-significant IgE levels in the positive control. In contrast to whey-mice, pWH-A treated mice showed no acute skin response, mMCP-1 release or change in body temperature upon whey challenge in all centers, which corresponds with the absence of anaphylactic shock symptoms in both the mouse and guinea pig model. pWH-B and -C induced anaphylactic shock symptoms in the guinea-pig and mice whereas results on the remaining allergic outcomes in mice were inconclusive. No differences in microbiota composition were measured in response to the challenge and Microbiota composition depended on the location of the centers. ConclusionsBoth animal models showed comparable results on the residual allergenicity of partial hydrolyzed whey proteins, but none of the centers was able to differentiate between the residual sensitizing capacities of the pWH-B and -C based on a single elicitation parameter in the murine model. Differences in microbiota composition might contribute to the robustness of the food allergy murine model. For a well-balanced prediction on the potential allergenicity of hydrolyzed infant formulas a multiple murine parameter model is suggested to decrease the risk of false positive or false negative results. A future challenge is to develop an overall scoring system for proper risk assessment, taking all parameters into account.

P615 Safety of vedolizumab in the treatment of IBD in a single tertiary centre

Abstract Background There is a lot of data on Vedolizumab efficacy in the treatment of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD). Despite this, we have little real-world data on its adverse reactions. We aimed to identify and quantify principal adverse reactions in order to assess the safety of the drug. Methods UC and CD patients from a single tertiary IBD referral centre receiving Vedolizumab treatment between September 2016 and August 2019 were included. Data were collected prospectively at week 22, 54 and 108. Adverse events were categorised as infections, rheumatic/cutaneous disorders, allergy-related symptoms/anaphylactic shock, serious adverse events and drug discontinuation. Serious adverse events were those that resulted in hospitalisation or death. Discontinuation was due to drug-related effects or IBD complications that persisted despite the treatment or that could be worsened by drug-induced immunodepression. Results Our analysis comprised 200 patients (86 with UC and 114 with CD: 22% female; median age 58,3 years). Adverse effects were reported in 59/200 (29,5%) patients, leading to treatment discontinuation in 21/200 (10,5%) cases: 2 with UC and 19 with CD. Six patients experienced more the one adverse reaction for a total of 69. Rheumatic disorders were observed in 17/69 (24,6%), infections in 17/69 (24,6%) and cutaneous manifestations in 6/69 (8,7%). One patient complained of headache and another subocclusive symptom. One patient had an asymptomatic increase in cholestasis tests. No anaphylactic shock or allergy-related symptoms were reported while 6 patients (6/69, 8,7%) required hospitalisation (especially for infective complications). Vedolizumab discontinuation was due to perianal disease onset or relapse (9/21, 42,8%), infections (6/21, 28,6%) and rheumatic disorders (5/21, 23,8%); in one case we observed uncontrolled hypertension and Ménière syndrome. Treatment was restarted after surgical management and treatment with antibiotics in 3 patients with perianal disease and 1 with community-acquired pneumonia, respectively. Conclusion In our experience, Vedolizumab is a well-tolerated drug. Most of the adverse events that occurred in our centre were mild and did not require hospitalisation. In some patients discontinuation was not permanent: we performed it in order to treat the condition that contraindicated the administration and restart treatment.

Allergenicity reduction and rheology property of Lactobacillus-fermented soymilk.

This study aimed to investigate the reduction in the potential allergenicity of soymilk, and its rheological properties, after fermentation with Lactobacillus. Soymilk (SM) was fermented with Lactobacillus brevis and Lactobacillus sp. The molecular weight of fermented soymilk (FSM) was characterized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and the potential allergenicity of FSM was analyzed using enzyme-linked immunosorbent assay in vitro and the BALB/c mouse model to detect changes in histamine, mouse mast cell protease-1 (mMCP-1), allergen-specific IgG/IgE, and cytokine levels and histomorphology of jejunum in vivo. The SDS-PAGE and enzyme linked immunosorbent assay (ELISA) showed that allergens of soybean (β-conglycinin and acidic subunit of glycinin) were almost degraded, and their immunoreactivity was decreased. In the BALB/c mouse model, the FSM group did not show anaphylactic shock symptoms compared with the SM group. Moreover, a tendency toward decreased serum allergen-specific IgG/IgE levels, plasma histamine levels, and mMCP-1 concentrations was observed in the FSM group. Furthermore, Th2-related cytokines were decreased, while IFN-γ production increased in spleen cell cultures. The intestinal villus was slightly damaged after the challenge. All these findings indicated that the Th1/Th2 balance in the FSM group shifted toward a Th1 response, ultimately reducing the potential allergenicity of FSM. Rheological assessment suggested that FSM has good viscous and pseudoplastic properties. Fermentation might be a promising method for producing tasty, hypoallergenic soybean products. © 2019 Society of Chemical Industry.

Milk processing increases the allergenicity of cow's milk-Preclinical evidence supported by a human proof-of-concept provocation pilot.

BackgroundSeveral studies demonstrated the adverse effect of milk processing on the allergy‐protective capacity of raw cow's milk. Whether milk processing also affects the allergenicity of raw milk is hardly investigated.ObjectiveTo assess the allergenicity of raw (unprocessed) and processed cow's milk in a murine model for food allergy as well as in cow's milk allergic children.MethodsC3H/HeOuJ mice were either sensitized to whole milk (raw cow's milk, heated raw cow's milk or shop milk [store‐bought milk]) and challenged with cow's milk protein or they were sensitized and challenged to whey proteins (native or heated). Acute allergic symptoms, mast cell degranulation, allergen‐specific IgE levels and cytokine concentrations were determined upon challenge. Cow's milk allergic children were tested in an oral provocation pilot with organic raw and conventional shop milk.ResultsMice sensitized to raw milk showed fewer acute allergic symptoms upon intradermal challenge than mice sensitized to processed milk. The acute allergic skin response was low (103 ± 8.5 µm vs 195 ± 17.7 µm for heated raw milk, P < 0.0001 and vs 149 ± 13.6 µm for shop milk, P = 0.0316), and there were no anaphylactic shock symptoms and no anaphylactic shock‐induced drop in body temperature. Moreover, allergen‐specific IgE levels and Th2 cytokines were significantly lower in raw milk sensitized mice. Interestingly, the reduced sensitizing capacity was preserved in the isolated native whey protein fraction of raw milk. Besides, native whey protein challenge diminished allergic symptoms in mice sensitized to heated whey proteins. In an oral provocation pilot, cow's milk allergic children tolerated raw milk up to 50 mL, whereas they only tolerated 8.6 ± 5.3 mL shop milk (P = 0.0078).Conclusion and Clinical RelevanceThis study demonstrates that raw (unprocessed) cow's milk and native whey proteins have a lower allergenicity than their processed counterparts. The preclinical evidence in combination with the human proof‐of‐concept provocation pilot provides evidence that milk processing negatively influences the allergenicity of milk.

Non-digestible oligosaccharides scFOS/lcFOS facilitate safe subcutaneous immunotherapy for peanut allergy

BackgroundImproving the safety of subcutaneous immunotherapy (SCIT) for food allergy is necessary to reduce side effects and achieve long-term tolerance. We determined the effect of dietary supplementation with 1% non-digestible short- and long-chain fructo-oligosaccharides (scFOS/lcFOS) on safety and efficacy of SCIT using a peanut allergy mouse model.MethodsAfter sensitization, mice received a scFOS/lcFOS or control diet for the rest of the study. To study safety of SCIT, mice were dosed with a single subcutaneous injection of peanut extract (PE) or PBS. To study efficacy, mice were dosed subcutaneously (SCIT, 3 times/week) with PE or PBS for 3 weeks. Hereafter, acute allergic skin responses, anaphylactic shock symptoms and body temperature were assessed. To study the mechanism in vitro, the human IgE receptor (FcεRI)-transfected rat mast cell (RBL) line was sensitized with an oligoclonal pool of chimeric human (chu)IgE antibodies against bovine β-lactoglobulin (BLG) and incubated with the oligosaccharides before exposure to BLG to assess direct the effect on degranulation.ResultsscFOS/lcFOS reduced anaphylaxis caused by a single PE SCIT dose. scFOS/lcFOS alone also reduced the acute allergic skin response. Moreover, scFOS/lcFOS supplementation resulted in lower MMCP-1 levels in serum after PE SCIT dose compared to control diet, while antibody levels were not affected by the diet. In vitro incubation with scFOS/lcFOS at 0.5% suppressed the degranulation of IgE-sensitized RBL cells. However, dietary supplementation with scFOS/lcFOS did not improve the efficacy of SCIT.ConclusionsWe show that scFOS/lcFOS diet improves the safety of SCIT, as evidenced by lower anaphylactic responses without compromising the efficacy in a mouse model for peanut allergy. This effect is likely to result from the suppression of mast cell effector function.

The efficacy of oral and subcutaneous antigen-specific immunotherapy in murine cow\u2019s milk- and peanut allergy models

Background Antigen-specific immunotherapy (AIT) is a promising therapeutic approach for both cow’s milk allergy (CMA) and peanut allergy (PNA), but needs optimization in terms of efficacy and safety.AimCompare oral immunotherapy (OIT) and subcutaneous immunotherapy (SCIT) in murine models for CMA and PNA and determine the dose of allergen needed to effectively modify parameters of allergy.MethodsFemale C3H/HeOuJ mice were sensitized intragastrically (i.g.) to whey or peanut extract with cholera toxin. Mice were treated orally (5 times/week) or subcutaneously (3 times/week) for three consecutive weeks. Hereafter, the acute allergic skin response, anaphylactic shock symptoms and body temperature were measured upon intradermal (i.d.) and intraperitoneal (i.p.) challenge, and mast cell degranulation was measured upon i.g. challenge. Allergen-specific IgE, IgG1 and IgG2a were measured in serum at different time points. Single cell suspensions derived from lymph organs were stimulated with allergen to induce cytokine production and T cell phenotypes were assessed using flow cytometry.ResultsBoth OIT and SCIT decreased clinically related signs upon challenge in the CMA and PNA model. Interestingly, a rise in allergen-specific IgE was observed during immunotherapy, hereafter, treated mice were protected against the increase in IgE caused by allergen challenge. Allergen-specific IgG1 and IgG2a increased due to both types of AIT. In the CMA model, SCIT and OIT reduced the percentage of activated Th2 cells and increased the percentage of activated Th1 cells in the spleen. OIT increased the percentage of regulatory T cells (Tregs) and activated Th2 cells in the MLN. Th2 cytokines IL-5, IL-13 and IL-10 were reduced after OIT, but not after SCIT. In the PNA model, no differences were observed in percentages of T cell subsets. SCIT induced Th2 cytokines IL-5 and IL-10, whereas OIT had no effect.ConclusionWe have shown clinical protection against allergic manifestations after OIT and SCIT in a CMA and PNA model. Although similar allergen-specific antibody patterns were observed, differences in T cell and cytokine responses were shown. Whether these findings are related to a different mechanism of AIT in CMA and PNA needs to be elucidated.

Characterization of the potential allergenicity of irradiated bovine α-lactalbumin in a BALB/c mouse model

Bovine α-lactalbumin (ALA) is a known food allergen present in milk to induce anaphylaxis. A previous study demonstrated that irradiated ALA (iALA) decreased the IgE-binding properties and weakened the degranulation capacity of basophils in vitro. The present study aimed to further assess the potential allergenicity of iALA in vivo in a BALB/c mouse model. The mice (n = 10/group) were intragastrically sensitized and orally challenged with either iALA or ALA using cholera toxin as adjuvant. In contrast to the ALA group, the iALA group did not show anaphylactic shock symptoms. A tendency toward decreased serum allergen-specific IgG/IgG1/IgE levels, plasma histamine levels and mast cell protease-1 (mMCP-1) concentrations in the iALA group were also observed, accompanied by a decrease in Th2-related cytokine levels and an increase of IFN-γ production in spleen cell cultures. Moreover, the peritoneal mast cell surface expression of FcεRI and peripheral blood basophil CD200R+ expression were decreased by 64.3% and 35.19%, respectively. Conversely, the percentage of CD4+CD25+Foxp3+ regulatory T cells increased in the iALA group. All of these findings indicated that iALA induces a shift toward the Th1 response, which ultimately reduces its potential allergenicity.

Post-sensitization administration of non-digestible oligosaccharides and Bifidobacterium breve M-16V reduces allergic symptoms in mice.

To support dietary management of severe cow's milk allergic infants, a synbiotic mixture of non‐digestible oligosaccharides and Bifidobacterium breve M‐16V (B. breve) was designed from source materials that are completely cow's milk‐free. It was investigated whether this specific synbiotic concept can reduce an established food allergic response in a research model for hen's egg allergy. Mice were orally sensitized once a week for 5 weeks to ovalbumin (OVA) using cholera toxin (CT) as an adjuvant. Non‐sensitized mice received CT in PBS only. Sensitized mice were fed a control diet or a diet enriched with short‐chain‐ (scFOS) and long‐chain fructo‐oligosaccharides (lcFOS), B. breve or scFOSlcFOS + B. breve for 3 weeks starting after the last sensitization. Non‐sensitized mice received the control diet. Anaphylactic shock symptoms, acute allergic skin responses and serum specific IgE, mMCP‐1 and galectin‐9 were measured upon OVA challenge. Activated Th2‐, Th1‐cells and regulatory T‐cells were quantified in spleen and mesenteric lymph nodes (MLN) and cytokine profiles were analyzed. Short chain fatty acids (SCFA) were measured in ceacal samples. The acute allergic skin response was reduced in mice fed the scFOSlcFOS + B. breve diet compared to mice fed any of the other diets. A reduction in mast cell degranulation (mMCP‐1) and anaphylactic shock symptoms was also observed in these mice. Unstimulated splenocyte cultures produced increased levels of IL10 and IFNg in mice fed the scFOSlcFOS + B. breve diet. Correspondingly, increased percentages of activated Th1 cells were observed in the spleen. Allergen‐specific re‐stimulation of splenocytes showed a decrease in IL5 production. In summary; post‐sensitization administration of scFOSlcFOS + B. breve was effective in reducing allergic symptoms after allergen challenge. These effects coincided with changes in regulatory and effector T‐cell subsets and increases in the SCFA propionic acid. These results suggest immune modulatory benefits of dietary intervention with a unique combination of scFOSlcFOS + B. breve in established food allergy. Whether these effects translate to human applications is subject for ongoing clinical studies.

Allergenicity characteristics of germinated soybean proteins in a BALB/c mouse model

Soybean proteins are widely used in many food products. However they also commonly cause food allergy. This study aimed to characterize the allergenicity of germinated soybean proteins in a BALB/c mouse model. Mice were orally sensitized with germinated soybean proteins or soybean proteins using cholera toxin as adjuvant. Anaphylactic shock reactions as well as changes in body temperature, specific antibody levels, mast cell protease-1 (mMCP-1) concentrations, morphological structure of duodenum, and cytokines were determined after the mice were challenged with germinated soybean proteins or soybean proteins. In contrast to soybean proteins, oral sensitization to germinated soybean proteins did not result in anaphylactic shock symptoms or decreased body temperature in mice. However, a minor damage of the intestinal villus existed after the challenge. A tendency toward decreased allergen-specific IgE, IgG and IgG1 levels, and mMCP-1 concentration was observed, accompanied by a repression of IL-4, IL-5, IL-13 and IFN-γ production in spleen cell cultures. Results indicate that germinated soybean proteins did not provoke remarkable allergic reactions compared to soybean proteins. Germinated soybean proteins have the potential to be a safe dietary formula for humans at risk of soybean allergy. However, additional studies on the underlying mechanisms and clinical trials are necessary.

Literature analysis of Acanthopanax anaphylactic shock in China

The aims of this study are to investigate the occurrence characteristics of Acanthopanax (刺五加 cì wǔ jiā) anaphylactic shock and to provide objective evidence for the rational use of the medicine. Fifty-seven cases of Acanthopanax anaphylactic shock were collected from several professional databases in China. The statistical data of the patients were analyzed with Visual FoxPro 6.0 and Office Excel 2003 by Microsoft (Redmond, WA, USA). The male:female incidence ratio was 0.5:1. Fifty-six (98.25%) patients were older than 30 years. Thirty-nine (68.42%) patients had an unknown allergy history. Nine (15.79%) patients used Acanthopanax for unlabeled indications. In most (98.25 %) patients, Acanthopanax was used in the form of dosage injection. Anaphylactic shock occurred within 30 minutes after treatment in 52 (94.54%) patients, and all episodes occurred during the infusion process. In two (3.51%) patients, the episode occurred when they used Acanthopanax for the second time. In one (1.75%) patient, the episode occurred during the third time of use. The clinical symptoms of anaphylactic shock are diversified, but all patients presented with cardiovascular and respiratory system symptoms. Acanthopanax injections that led to anaphylactic shock were produced exclusively by four manufacturers. Four (7.02%) patients died and 49 (85.96%) patients were cured, but the status of four patients is unknown. Because an Acanthopanax injection may cause anaphylactic shock and can be fatal in severe cases, physicians and patients must pay close attention to using it rationally. Clinicians should carefully consult the allergic constitution of their patients, strictly follow the guidelines of the drug, use Acanthopanax in the oral dosage form as much as possible, and strengthen therapeutic monitoring.

Interlaboratory evaluation of a cow's milk allergy mouse model to assess the allergenicity of hydrolysed cow's milk based infant formulas

This study describes two phases of a multi-phase project aiming to validate a mouse model for cow's milk allergy to assess the potential allergenicity of hydrolysed cow's milk based infant formulas (claim support EC-directive 2006/141/E). The transferability and the discriminatory power of this model was evaluated in 4 research centers. Mice were sensitized by oral gavage with whey or extensively hydrolysed whey (eWH) using cholera toxin as an adjuvant. Whey-specific antibodies, mMCP-1 levels, anaphylactic shock symptoms, body temperature and the acute allergic skin response were determined upon whey challenge. In phases I and II, all 4 centers detected elevated levels of whey-specific IgE/IgG1 in whey sensitized animals. Elevated levels of mMCP-1, anaphylactic symptoms, body temperature drop and acute allergic skin response were scored upon whey challenge in 3 out of 4 research centers. In contrast, none of the evaluated parameters were elevated in eWH orally exposed groups. The cow's milk allergy mouse model is capable to distinguish the sensitizing capacity of complete or hydrolysed cow's milk protein. The model uses straightforward parameters relevant to food allergic responses and can be effectively transferred between different laboratories. We propose this mouse model as a new strategy for the screening of new hypoallergenic cow's milk formulas.

The basophil activation test identified carminic acid as an allergen inducing anaphylaxis

T0 THE EDITOR: In the autumn of 2011, a 39-year-old Japanese woman was referred for evaluation of allergic reactions after ingestion of a commercial bottled supplement that contained vitamin Bs and C and fruit flavors. The reactions occurred 3 times, at 1-month intervals. The first 2 episodes were mild and consisted of an itchy throat and localized hives on her lower extremities. However, after drinking the aforementioned supplement every day for 3 months, she manifested more severe symptoms of anaphylactic shock, with an itchy throat, generalized urticaria, diarrhea, and low blood pressure. Interestingly, each of the allergic reactions was associated with her menstrual period; the episodes occurred within 3 days before or after the beginning day of menstruation. Skin prick tests were negative for the supplement. An intradermal test showed that a 10-fold dilution of the solution was an irritating concentration that elicited reactions in the patient and all 4 of the tested controls; lower, nonirritating concentrations showed negative intradermal results. We then tried the in vitro basophil activation test (BAT), which analyzes surface activation marker CD203c expression on basophils. Importantly, the drink itself and, among its constituents, only cochineal dye gave clearly positive results in BAT with the use of the patient’s blood, but not nonallergic subjects’ blood. BAT was highly sensitive and selective, because obvious induction of basophil surface CD203c was observed with 10to 640-fold dilutions of the supplement, the corresponding dose of cochineal dye and its main constituent, carminic acid (purity 97%), but not with a protein extracted from Coccus cacti (Figure 1). In vitro sensitization experiments showed that carminic acideinduced basophil activation was IgE-mediated, because passive sensitization of a normal donor’s basophils by the patient’s serum was completely blocked by the presence of an antiIgE antibody, omalizumab (Figure 2). On the basis of these results, the patient was strongly discouraged from consuming drinks and foods that contained cochineal dye. She has subsequently experienced no further anaphylactic episodes. Although confirmatory challenge was unable to be performed to prove causation because the patient refused to undergo this test, on the basis of her BAT and the absence of anaphylaxis when she avoided carminic acid, we believe that carminic acid, in association with her menstrual cycle, was responsible for her anaphylaxis. Cochineal dye is usually regarded as a highly safe material, and it is widely used as a food additive and cosmetic ingredient. To date, type I allergy due to the dye, including anaphylaxis, urticarial, and occupational asthma, has been reported only occasionally. Allergy to cochineal dye is generally because of a hypersensitivity reaction to a contaminating protein (ie, CC38K, a phospholipase), whereas allergy to the main compound, carminic acid, is rare. Carminic acid is a relatively small molecule (molecular weight 492) that is thought to exhibit allergenicity as a protein-bound hapten. Although skin tests are usually sensitive and useful for allergen determination, they sometimes cause nonspecific skin stimulation. This limits the reliability of the tests, as in our present patient. Here, we were impressed by the finding that BAT accurately identified the allergen. That is, the test clearly showed that the patient’s own basophils, but not those of nonallergic donors, responded to highly pure carminic acid but not to a protein extracted from Coccus cacti. Furthermore, the patient’s basophils showed an obvious response to the allergen in BAT during menstruation, compared with the rest of the menstrual cycle (Figure 1, E); this result was in clear contrast to the absence of any menstruation-related enhancement of a response to polyclonal anti-IgE antibody. On the basis of these results, we believe that an in vitro BAT with the use of peripheral blood would be highly useful for analyzing cochineal dye-induced allergy. At present, we do not know the exact mechanism(s) underlying menstruation-associated changes in the basophil response; overnight culture of our patient’s cells with estradiol or progesterone at 1 mmol/L failed to modulate the response to carminic acid. Recent progress in the pathogenesis of allergies has strongly implicated not only mast cells but also basophils as being critically involved in several allergic responses. Flow cytometric assessment of surface markers, including CD203c, has enabled precise determination of the activation status of basophils. In regard to carminic acid-related allergy, our present results suggest that basophils are highly sensitive to this allergen and that the cells might behave as a key initiator/effector in vivo. Thus, future analyses of the basophil activation status during clinical anaphylaxis will be important for elucidating the involvement of this cell type in this allergic reaction.

Sensitizing capacity and allergenicity of enzymatically cross-linked sodium caseinate in comparison to sodium caseinate in a mouse model for cow's milk allergy

A transglutaminase cross-linked caseinate was designed for use in dairy products to increase the viscosity of food matrices. The difference in structure of cross-linked caseinate might have implications for the risk of developing cow's milk allergy. The sensitizing capacity and the allergenicity (the potency to induce an allergic effector response) of cross-linked sodium caseinate was investigated using a mouse model for cow's milk allergy.Mice were orally sensitized with cross-linked caseinate or caseinate using cholera toxin as adjuvant. Anaphylactic shock reactions, change in body temperature, acute allergic skin response, caseinate-, cross-linked caseinate-IgE and mMCP-1 concentrations were determined after challenge with cross-linked caseinate or caseinate. Sensitization with cross-linked caseinate did not result in anaphylactic shock symptoms, drop in body temperature or release of serum mMCP-1. A tendency toward decreased casein-specific IgE levels was observed. The allergenicity did not differ between both products. These results indicate that in already caseinate-sensitized mice, cross-linked caseinate did not provoke more pronounced allergenic reactions compared to sodium caseinate. On top of that, reduced sensitization to cross-linked caseinate was observed. Cross-linked caseinate might therefore be an interesting new dietary concept for humans at risk for food allergy although more mechanistic studies and clinical trials are needed for validation.

Influence of MRI contrast media on histamine release from mast cells

Mast cells, owing to diversity of secreted mediators, play a crucial role in the regulation of inflammatory response. Together with basophils, mast cells constitute a central pathogenetic element of anaphylactic (IgE-dependent) and anaphylactoid (IgE-independent) reactions. In severe cases, generalized degranulation of mast cells may cause symptoms of anaphylactic shock. The influence of the classical, iodine-based contrast media on mastocyte degranulation has been fully described. Our objective was to determine the influence of the gadolinium-based MRI contrast media on histamine release from mast cells and to compare the activity of ionic and non-ionic preparations of contrast media. To determine the intensity of mast cell degranulation, we used an experimental model based on mastocytes isolated from rat peritoneal fluid. Purified suspensions of mast cells were incubated with various concentrations of Gd-DTPA and Gd-DTPA-BMA, and solutions of PEG 600 which served as a non-toxic osmotic stimulus. The intensity of mast cell activation was presented as mean percentage of histamine released from cells after incubation. The obtained results demonstrate that both ionic and non-ionic preparations of the MRI contrast media are able to induce mast cell degranulation in vitro. It was also proved that the non-ionic MRI contrast media stimulate mast cells markedly more weakly than ionic contrast media at identical concentration. The aforementioned results may suggest a more profitable safety profile of the non-ionic contrast preparations. We may also conclude that triggering of mast cell degranulation after incubation with the solutions of MRI contrast media results from non-specific osmotic stimulation and direct toxicity of free ionic residues.

The effect of enteral supplementation of neutral and acidic oligosaccharides on immunoglobulin free light chains in preterm infants

This study describes two phases of a multi-phase project aiming to validate a mouse model for cow's milk allergy to assess the potential allergenicity of hydrolysed cow's milk based infant formulas (claim support EC-directive 2006/141/E). The transferability and the discriminatory power of this model was evaluated in 4 research centers. Mice were sensitized by oral gavage with whey or extensively hydrolysed whey (eWH) using cholera toxin as an adjuvant. Whey-specific antibodies, mMCP-1 levels, anaphylactic shock symptoms, body temperature and the acute allergic skin response were determined upon whey challenge. In phases I and II, all 4 centers detected elevated levels of whey-specific IgE/IgG1 in whey sensitized animals. Elevated levels of mMCP-1, anaphylactic symptoms, body temperature drop and acute allergic skin response were scored upon whey challenge in 3 out of 4 research centers. In contrast, none of the evaluated parameters were elevated in eWH orally exposed groups. The cow's milk allergy mouse model is capable to distinguish the sensitizing capacity of complete or hydrolysed cow's milk protein. The model uses straightforward parameters relevant to food allergic responses and can be effectively transferred between different laboratories. We propose this mouse model as a new strategy for the screening of new hypoallergenic cow's milk formulas.

The effect of splenectomy on the production of anaphylactic shock in the guinea pig and the rat.

AbstractSplenectomy in the guinea pig affords protection against active anaphylactic shock, if the operation is performed a short time before the challenge with antigen. When the challenge is made under ether anaesthesia, the maximal protective action is present 24 hours after splenectomy but is lost during the next 48 hours. If the challenge is made under urethane anaesthesia, the protective action is present 72 hours after the operation. The mechanism of the protective action of splenectomy is not clear, although it may be due to a loss of tissue antibodies or of complement since passive anaphylaxis is not altered by the operation. In contrast, removal of the spleen in the rat fails to modify the symptoms of anaphylactic shock.