Minimal impact of low-density lipoprotein apheresis on vancomycin serum concentration: A case report.

Low-density lipoprotein apheresis (LDL-A) is a blood purification therapy used to treat refractory ulcers in patients with arteriosclerosis obliterans. We describe a case of vancomycin treatment in a patient undergoing maintenance hemodialysis and LDL-A therapy and assess its impact on serum vancomycin concentration. The patient underwent LDL-A twice a week (Mondays and Fridays) and maintenance dialysis three times a week (Tuesdays, Thursdays, and Saturdays) for diabetic nephropathy associated with type 1 diabetes mellitus. Following the wound culture results, vancomycin was initiated with a 1.75 g administration post-dialysis. Serum vancomycin levels before and after LDL-A, measured on the subsequent day, exhibited only slight fluctuations within the intermeasurement variability range. Despite continuing vancomycin administration at the standard dose in patients undergoing hemodialysis, the serum concentration remained consistent, suggesting a minimal impact of LDL-A on vancomycin pharmacokinetics.

Extravasation of Noncytotoxic Agents: Skin Injury and Risk Classification.

Extravasations are common manifestations of iatrogenic injuries associated with intravenous therapy. Cytotoxic agents are already subject to a relatively well-defined management strategy in healthcare institutions and classified into three groups according to the extent of damage from extravasation: vesicants, irritants, and non-tissue-damaging agents. Therefore, careful monitoring and initial treatment according to the severity of the skin injury decreases the incidence of extravasation injury. In contrast, high osmolarity, acidic or alkaline, and/or vasoconstrictive activity have all been suggested as possible causes of tissue injury due to the extravasation of noncytotoxic agents. However, the severity of the injuries has not been classified. Therefore, due to a lack of awareness, case reports of severe extravasation injury caused by noncytotoxic agents are increasing. In this paper, we review case reports and animal experiments and classify the severity of extravasation injury by noncytotoxic agents into three categories. Parallel to cytotoxic agents, the classification provides appropriate warning of possible injury severity, helping medical personnel better understand the severity of tissue damage and prevent injury severity during extravasation.

Classification of Skin Injury Risk Caused by Extravasation of Electrolyte Solutions or Infusions in a Rat Model.

Cytotoxic agents are classified according to the severity of skin injury after extravasation. However, injuries caused by extravasation of noncytotoxic agents have not been sufficiently investigated, although the risk of extravasation is mentioned in medical safety information published by the Japan Council for Quality Health Care. Therefore, in this study, we focused on noncytotoxic electrolyte solutions and infusions and evaluated skin injuries during leakage using extravasation model rats. Rats were anesthetized and intradermally injected with 100 µL of an electrolyte solution or infusion. Injection lesions were macroscopically and histopathologically evaluated for extravasation injuries. Each electrolyte solution and infusion were classified into three categories (vesicants, irritants, and non-tissue-damaging agents) depending on the degree of skin injury. Similar to saline, 0.3% potassium chloride and 0.6% magnesium sulfate showed almost no injury, and 3% sodium chloride and BFLUID® caused erythema and induration. Erythema, induration, and ulceration were observed with the following: 10% sodium chloride, 2% calcium chloride, 8.5% calcium gluconate, 12.3% magnesium sulfate, MAGSENT®, FESIN®, and Intralipos®. The duration of damage with these agents was markedly prolonged. Electrolyte solutions and infusions can be classified into vesicants (10% sodium chloride, 2% calcium chloride, 8.5% calcium gluconate, 12.3% magnesium sulfate, MAGSENT®, FESIN®, and Intralipos®), irritants (3% sodium chloride and BFLUID®), and non-tissue-damaging agents (0.3% potassium chloride and 0.6% magnesium sulfate) according to their composition. The characteristic symptoms and severity of each drug extravasation revealed in this study will provide basic information for preparation of guidelines for treatment of extravasation.

A novel detection method for cross-linking of IgE-receptors by autoantibodies in chronic spontaneous urticaria.

BACKGROUND: Autoantibodies (AAbs) against immunoglobulin E (IgE) antibodies (Abs) and their high-affinity receptor alpha subunits (FcεRIα) are key factors in the elicitation of type IIb autoimmune chronic spontaneous urticaria (type IIb aiCSU). In this study, we aimed to develop a new method to detect functional anti-FcεRIα and anti-IgE AAbs, which can crosslink the plural FcεRІα molecules and IgE Abs on the surface of mast cells and basophils, in sera from aiCSU patients using the amplified luminescence proximity homogeneous assay (Alpha). METHODS: Sera were obtained from 14 aiCSU patients, as diagnosed by recurrent chronic spontaneous urticaria episodes and positive results for the autologous serum skin test and/or histamine release test (HRT). The AAbs to FcεRIα and IgE Abs were determined in sera from aiCSU patients using enzyme-linked immunosorbent assay (ELISA) and Alpha by cross-linking (AlphaCL) of IgE Abs and/or FcεRІα. RESULTS: Serum anti-FcεRIα and anti-IgE AAb levels were not significantly different between aiCSU patients and healthy subjects in ELISA. Anti-FcεRIα AAbs were detected in 10 of 14 aiCSU patients who displayed positive (5/5) and negative (5/9) results in the HRT for anti-FcεRIα AAbs by AlphaCL, whereas no signals were observed in healthy subjects. Additionally, anti-IgE AAbs were detected in two of four aiCSU patients who displayed positive results in the HRT for anti-IgE AAbs. CONCLUSIONS: A new assay method using AlphaCL can detect anti-FcεRIα and anti-IgE AAbs with FcεRIα- and IgE-crosslinking abilities in sera from aiCSU patients. This simple and practical assay method may be available as a diagnostic tool for urticaria patients.

Low Serum Albumin Level Is a Risk Factor for Delayed Methotrexate Elimination in High-Dose Methotrexate Treatment.

BACKGROUND: In high-dose methotrexate (HD-MTX) therapy, delayed elimination of MTX from plasma leads to severe adverse effects. However, the risk factors for the delayed elimination of plasma MTX are still unclear. OBJECTIVE: The purpose of this study was to investigate the factors related to the delayed MTX elimination in HD-MTX monotherapy. METHODS: This retrospective study was performed on patients who received HD-MTX monotherapy between April 2009 and March 2019 at the Hiroshima University Hospital. Patients were divided into a "Normal" and a "Delayed" group according to their MTX plasma concentration at 48 or 72 hours after administration. Patient characteristics, dose of HD-MTX, MTX plasma concentration, and adverse effects were analyzed and compared between the 2 groups. RESULTS: A total of 74 patients were included in this study. Logistic analysis of patient baseline characteristics was performed to identify risk factors for delayed MTX elimination. Serum albumin (ALB) was detected as a risk factor. Univariate and multivariate analysis revealed that low ALB level (<3.7 g/dL) and type of cancer were associated with delayed MTX elimination (univariate analysis: odds ratio [OR] = 6.00, P = 0.004, and OR = 4.33, P = 0.039, respectively; multivariate analysis: adjusted OR [AOR] = 6.45, P = 0.006, and AOR = 8.11, P = 0.018, respectively). Adverse effects were not significantly different between the 2 groups, excluding renal impairment. CONCLUSIONS AND RELEVANCE: Our study showed that low ALB is a risk factor for delayed MTX elimination in HD-MTX monotherapy. Pharmacokinetic analysis is needed to establish the dose of HD-MTX in patients with a low ALB level.

Differences in Pharmaceutical Intervention Triggers for the Optimization of Medication by Patient Age: A University Hospital Study.

Optimization of medication therapy for the elderly is a matter of rapidly growing importance, which is addressed by pharmacists through comprehensive reviews. In this study, the impact of medication review by pharmacists on medication optimization and avoidance of adverse drug events (ADE) was investigated, as well as differences in the triggers for pharmaceutical intervention to allow for optimization of medication by patient age. Data for this study were collected from reports recorded between April 2013 and March 2019 for patients admitted to the Hiroshima University Hospital. In response to pharmacists' proposals, prescriptions were modified in 18932 cases, comprising 17% of the total 111479 patients during hospitalization. The frequency of such intervention was higher in elderly patients aged ≥65 years than in those <65 years (20 vs. 14%, p < 0.01). The reasons for pharmacists' intervention were primarily (67%) medication history or clinical symptoms in all age groups. Patient complaint was a minor reason in patients aged ≥75 years, accounting for only 2% of all interventions; laboratory results were a more typical reason, accounting for 24% of all interventions. These findings reveal the importance of pharmacists' interventions for optimizing medication and preventing ADEs, particularly in elderly patients. Thus, pharmacists must evaluate the medications and conditions, including laboratory results, in the medical records of elderly patients more carefully than those of younger patients as elderly patients might be unable to communicate about subjective symptoms.

Identification of peroxidase-1 and beta-glucosidase as cross-reactive wheat allergens in grass pollen-related wheat allergy.

BACKGROUND: Some patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) or wheat allergy showed negative ω-5 gliadin-specific IgE test and high level of grass pollen-specific IgE. It was presumed that these patients developed allergic reaction upon cross-reaction of their IgE antibodies raised against grass pollen allergens to wheat allergens. This study aimed to clarify clinical characteristics and wheat allergens of this phenotype of WDEIA/wheat allergy, which were tentatively diagnosed as grass pollen-related wheat allergy (GPWA). METHODS: A total of six patients with GPWA were enrolled, and controls were 17 patients with grass pollen allergy but no episode of wheat allergy, and 29 patients with other wheat allergies: 18 with conventional WDEIA and 11 with hydrolyzed wheat protein allergy. Sensitization to wheat proteins was determined by basophil activation test (BAT). IgE-binding proteins in wheat flour were identified by immunoblotting followed by mass spectrometry. Wheat allergen-specific IgE tests were established by CAP-FEIA system. RESULTS: All the six patients with GPWA were sensitized to water-soluble wheat proteins in BAT and IgE-immunoblotting, and peroxidase-1 (35 kDa) and beta-glucosidase (60 kDa) were identified as specific IgE-binding wheat proteins. The binding of patient IgE to these proteins was inhibited by pre-incubation of patient sera with grass pollen. The peroxidase-1- and beta-glucosidase-specific IgE tests identified three and four of six patients with GPWA, respectively, but only two of 29 controls, indicating high specificity of these tests. CONCLUSIONS: Peroxidase-1 and beta-glucosidase are specific wheat allergens for GPWA among grass pollen allergy and other types of wheat-induced food allergies.

Exercise-induced allergic reactions on desensitization to wheat after rush oral immunotherapy.

BACKGROUND: The effect of oral immunotherapy (OIT) on wheat allergy is promising in terms of the potential to obtain desensitization; however, the frequency of exercise-induced allergic reactions on desensitization (EIARDs) and the associated risk factors remain to be determined. METHODS: Twenty-five patients underwent rush OIT for wheat allergy, and 21 achieved the full-dose intake of wheat products (5 g of wheat protein). Exercise-provocation tests were repeatedly performed after the ingestion of a full-dose wheat product. The time-course of the levels of the specific IgEs (sIgE) to wheat extract, total gliadin, deamidated gliadin, recombinant gliadin components (α/ß-, γ- and ω-5-), and glutenin (high and low molecular weight) components was analyzed using ImmunoCAP® , ELISA, or IgE immunoblotting. RESULTS: Fourteen patients (66.7%) were diagnosed as EIARD+, which remained 5 years after rush OIT in 11 patients (52.4%). There were no differences in the clinical backgrounds of the EIARD+ and EIARD- patients. However, EIARD+ patients showed significantly higher sIgE levels to all gliadin and glutenin components than EIARD- patients before OIT. The sIgE levels to each component decreased equally after 1 and 2 years of OIT. On IgE immunoblotting, sera from all patients reacted to the multiple gluten bands, and some reacted to the water-soluble bands. The intensity of all IgE-reactive bands also became equally lighter after OIT. CONCLUSIONS: EIARDs were frequently observed and remained for a long period after successful OIT for wheat allergy. None of the specific wheat components were found to contribute to EIARDs.

Vitamin A-coupled liposomal Rho-kinase inhibitor ameliorates liver fibrosis without systemic adverse effects.

AIM: Rho-kinase (ROCK) inhibitor could ameliorate liver fibrosis by suppressing hepatic stellate cell (HSC) activation. However, because systemic administration of ROCK inhibitor causes serious adverse effects, we developed a drug delivery system selectively delivering ROCK inhibitor to HSCs. Here, we examined whether our developed vitamin A (VA)-coupled liposomal ROCK inhibitor reduced liver fibrosis in rats without causing systemic adverse effects. METHODS: LX-2 HSCs were analyzed for morphological changes and the expression of profibrotic proteins. The inhibitory effects of VA-coupled liposomal ROCK inhibitor on liver fibrosis were confirmed in a rat model of liver fibrosis induced by i.p. injection of carbon tetrachloride. The degree of liver fibrosis, biochemical changes, and survival rates were also investigated. RESULTS: Vitamin A-coupled liposomal ROCK inhibitor had an effect at approximately 1/100 the amount of the free ROCK inhibitor for inhibiting the activation of LX-2 cells and caused significant decreases in the expression levels of α-smooth muscle actin (SMA) and transforming growth factor (TGF)-ß1. The degree of liver fibrosis was suppressed by treatment with VA-coupled liposomal ROCK inhibitor, and the expression of α-SMA and TGF-ß1 in liver tissues was also significantly suppressed. In addition, serum levels of alanine aminotransferase and hyaluronic acid were significantly reduced, and there was no decline in kidney function, which has been noted as a systemic adverse effect of ROCK inhibitor. Furthermore, VA-coupled liposomal ROCK inhibitor improved survival rates in rats with liver fibrosis. CONCLUSION: Vitamin A-coupled liposomal ROCK inhibitor efficiently suppressed liver fibrosis without causing systemic adverse effects.

Intestinal absorption of the wheat allergen gliadin in rats.

BACKGROUND: Aspirin enhances food allergy symptoms by increasing absorption of ingested allergens. The objective of this study is to elucidate the role of aspirin in facilitating intestinal absorption of the wheat allergen, gliadin, in rats. METHODS: Plasma concentrations of gliadin were determined after oral administration by gavage or administration into a closed intestinal loop in rats. We used an in situ intestinal re-circulating perfusion experiment to examine the effect of pepsin on aspirin-facilitated gliadin absorption. Fluorescein isothiocyanate (FITC)-labeled dextran-40 (FD-40) was used as a marker of non-specific absorption. The molecular size of gliadin and its allergenicity in plasma were examined using immunoblot analysis and intradermal reaction tests with Evans blue dye (EBD) extravasation, respectively. RESULTS: Aspirin increased plasma concentrations of gliadin after oral administration but had no effect in the closed intestinal loop study. An in situ intestinal re-circulating perfusion study showed that FITC-labeled gliadin was absorbed similarly to FD-40. Aspirin increased absorption of both intact and pepsin-digested gliadin, with a more significant effect on absorption of pepsin-treated gliadin. Immunoblotting showed that most gliadin was absorbed in intact form. When the gliadin fraction was extracted from rat plasma after gavage and injected intradermally into gliadin-sensitized rats, EBD extravasation was observed at injection sites in a gliadin dose-dependent manner. CONCLUSIONS: Aspirin increased the absorption of intact and pepsin-digested gliadin via the paracellular pathway, maintaining their allergenicity. Moreover, the effect of aspirin on gliadin absorption was enhanced by modification and digestion of gliadin in the stomach.

[A CASE OF FOOD-DEPENDENT EXERCISE-INDUCED ANAPHYLAXIS BY SHRIMP: FRUCTOSE 1, 6- BISPHOSPHATE ALDOLASE IS SUPPOSED AS CAUSATIVE COMPONENT DESPITE NEGATIVE ALLERGEN-SPECIFIC IGE TEST (IMMUNOCAP®)].

A 16-year-old male high-school student experienced generalized itchy wheal and dyspnea during physical exercise after lunch. Each food material of his lunch was examined using a prick-prick test, allergen-specific IgE test (ImmunoCAP®), and provocation test. The prick-prick test was positive for black tiger shrimp (raw and heated) and white leg shrimp (heated). Allergen-specific IgE test (ImmunoCAP®) showed absolutely negativity for all suspected foods. The food-exercise provocation test using heated black tiger shrimp with additional aspirin intake finally induced anaphylaxis.We studied the IgE-binding molecules from shrimp using a purification procedure and Western blotting, with sera from the patient and several controls. A 40-kDa protein, corresponding to FBA, was found to be the major IgE-binding allergen component in this patient. Currently, the precise history and the prick-prick test using both raw and heated shrimps are useful to diagnose shrimp-induced FDEIA. Because the allergen-specific IgE test is insufficient to diagnose the cause of the symptoms, a component allergen-specific IgE test after the identification of the causative allergenic protein, such as FBA, is required.

Evaluation of Risk of Injury by Extravasation of Hyperosmolar and Vasopressor Agents in a Rat Model.

Inadvertent leakage of noncytotoxic agents causes severe tissue injury. In this study, we macroscopically and histopathologically evaluated the extent of skin injury caused by extravasation of hyperosmolar or vasopressor agents in rats. Rats were intradermally administered saline (100 µL), the hyperosmolar agents mannitol (5-20 mg/100 µL) and glucose (5-50 mg/100 µL), or the vasopressors dopamine (2 mg/100 µL), adrenaline (0.1 mg/100 µL), and noradrenaline (0.1 mg/100 µL). Lesion size (erythema, induration, ulceration, and necrosis) was monitored after agent injection. Skin tissue biopsies were evaluated at 24 h after agent injection. Mannitol and glucose induced severe lesions in a concentration (and osmolarity)-dependent manner. Mannitol and glucose at 10-20% (w/v) induced inflammation, and lesions healed within 3-6 d. In contrast, ≥25% (w/v) glucose elicited severe skin lesions with ulceration and necrosis within 24 h, which healed gradually 16-22 d after injection. The severity of extravasation injury caused by vasopressors varied. Adrenaline and noradrenaline induced severe injury with ulceration and necrosis, which healed over 23.3 and 18.3 d, respectively. In contrast, dopamine induced erythema and induration, and damage duration was only 5.7 d. In conclusion, mannitol and glucose at osmolarities of 549-1098 and 833-1110 mOsm/L, respectively, can be classified as "irritants," while ≥1388 mOsm/L glucose can be classified as a "vesicant." As for vasopressors, adrenaline and noradrenaline can be classified as "vesicants" whereas dopamine can be classified as an "irritant."

Diversity in intracortical remodeling in the human femoral bone: A novel view point with the morphological analysis of secondary osteons.

INTRODUCTION: In humans, intracortical bone remodeling is performed by a basic multicellular unit (BMU) composed of osteoclasts and osteoblasts penetrating through cortical bones. As a result, secondary osteons and their boundaries, cement lines, can be observed on the transverse section. There have been few reports mention whether there is diversity within a single individual and on the relevance to bone remodeling. The purpose of this study is to investigate the morphological diversity of secondary osteons in human femoral bone and to examine the relationship with bone remodeling. MATERIAL AND METHODS: First of all, we developed an original method to get the cross-sectional images of the cortical bones around the whole circumference for the purpose of evaluating the morphology of the secondary osteon exhaustively. Then, a total of ten cross-sectional slices from one right human femoral bone of male were prepared and stained with this method. The osteon population density and complexity of cement lines in osteons were evaluated in detail. RESULTS: Within this femoral bone, the osteon population density was significantly higher in the periosteal side and in the posterior area. Conversely, the cement line density and the osteon complexity were higher in the endosteal side; the proportion of complexed osteon significantly increased from the periosteal side toward the endosteal side. DISCUSSION: The results suggested that there were diversities in osteon population densities and osteon morphological pattern within one human femoral bone. It seemed that the BMUs ran to avoid the existing regions of osteon in the periosteal sides and to overlap the existing osteon in the endosteal sides. This seemed to be one of the novel viewpoints in the morphological analysis of secondary osteons. It might be better for the orthopedic surgeons to be aware that the osteon distribution in the cortical bone is not uniform.

INSOLUBILITY AND ALTERATION OF ALLERGENIC ACTIVITY OF WHEAT PROTEINS IN PROCESSED FOODS.

BACKGROUND: Food processing causes decomposition, denaturation or polymerization of protein, which may alter an allergic reaction. This study aimed to investigate the insolubility and alteration of wheat allergens in processed foods and the reactivity to patient sera. METHODS: We extracted proteins from wheat flour, udon and bread using different extracts and conducted SDS-polyacrylamide gel electrophoresis. IgE-immunoblotting was also conducted using sera from children with wheat allergy. RESULTS: Soluble protein was extracted from wheat flour, and gluten fractions were also extracted by adding SDS. However, no proteins were able to be extracted from udon or bread witout severing the disulfide bonds under reducing condition. Only trace amounts of protein were detected in the water after boiling udon noodles. The reactivity of IgE antibody to the extracted protein did not differ among the different processed food types. CONCLUSIONS: Wheat allergens became strongly insolubilized after gluten formation and heating. However, the reactivity of IgE antibody to each allergen was not affected by food processing. Further studies are needed for the effects on clinical symptoms.

Stability of Adrenaline in Irrigating Solution for Intraocular Surgery.

Intraocular irrigating solution containing 1 µg/mL adrenaline is widely used during cataract surgery to maintain pupil dilation. Prepared intraocular irrigating solutions are recommended for use within 6 h. After the irrigating solution is admistered for dilution, the adrenaline may become oxidized, and this may result in a decrease in its biological activity. However, the stability of adrenaline in intraocular irrigating solution is not fully understood. The aim of this study was to evaluate the stability of adrenaline in clinically used irrigating solutions of varying pH. Six hours after mixing, the adrenaline percentages remaining were 90.6%±3.7 (pH 7.2), 91.1%±2.2 (pH 7.5), and 65.2%±2.8 (pH 8.0) of the initial concentration. One hour after mixing, the percentages remaining were 97.6%±2.0 (pH 7.2), 97.4%±2.7 (pH 7.5), and 95.6%±3.3 (pH 8.0). The degradation was especially remarkable and time dependent in the solution at pH 8.0. These results indicate that the concentration of adrenaline is decreased after preparation. Moreover, we investigated the influence of sodium bisulfite on adrenaline stability in irrigating solution. The percentage adrenaline remaining at 6 h after mixing in irrigating solution (pH 8.0) containing sodium bisulfite at 0.5 µg/mL (concentration in irrigating solution) or at 500 µg/mL (concentration in the undiluted adrenaline preparation) were 57.5 and 97.3%, respectively. Therefore, the low concentration of sodium bisulfite in the irrigating solution may be a cause of the adrenaline loss. In conclusion, intraocular irrigation solution with adrenaline should be prepared just prior to its use in surgery.

Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis.

BACKGROUND: Oral wheat plus cofactors challenge tests in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) produce unreliable results. OBJECTIVE: We sought to confirm WDEIA diagnosis by using oral gluten flour plus cofactors challenge, to determine the amount of gluten required to elicit symptoms, and to correlate these results with plasma gliadin levels, gastrointestinal permeability, and allergologic parameters. METHODS: Sixteen of 34 patients with a history of WDEIA and ω5-gliadin IgE underwent prospective oral challenge tests with gluten with or without cofactors until objective symptoms developed. Gluten reaction threshold levels, plasma gliadin concentrations, gastrointestinal permeability, sensitivities and specificities for skin prick tests, and specific IgE levels were ascertained in patients and 38 control subjects. RESULTS: In 16 of 16 patients (8 female and 8 male patients; age, 23-76 years), WDEIA was confirmed by challenges with gluten alone (n = 4) or gluten plus cofactors (n = 12), including 4 patients with previous negative wheat challenge results. Higher gluten doses or acetylsalicylic acid (ASA) plus alcohol instead of physical exercise were cofactors in 2 retested patients. The cofactors ASA plus alcohol and exercise increased plasma gliadin levels (P < .03). Positive challenge results developed after a variable period of time at peak or when the plateau plasma gliadin level was attained. Positive plasma gliadin threshold levels differed by greater than 100-fold and ranged from 15 to 2111 pg/mL (median, 628 pg/mL). The clinical history, IgE gliadin level, and baseline gastrointestinal level were not predictive of the outcomes of the challenge tests. The challenge-confirmed sensitivity and specificity of gluten skin prick tests was 100% and 96%, respectively. CONCLUSION: Oral challenge with gluten alone or along with ASA and alcohol is a sensitive and specific test for the diagnosis of WDEIA. Exercise is not an essential trigger for the onset of symptoms in patients with WDEIA.

Characterization of a hypoallergenic wheat line lacking ω-5 gliadin.

BACKGROUND: There is no curative treatment for wheat-dependent exercise-induced anaphylaxis (WDEIA). ω-5 Gliadin is one of the dominant allergens affecting WDEIA patients. The use of ω-5 gliadin-free wheat flour in the regular diet is considered one of the prophylactic approaches against the elicitation of allergic symptoms and sensitization to ω-5 gliadin. We sought to find hypoallergenic bread wheat (or common wheat) that lacked the genes encoding ω-5 gliadin and to evaluate its in vitro allergenicity. We also aimed to evaluate the sensitization ability of one of the selected hypoallergenic wheat lines by using a possible animal model of wheat allergy. METHODS: We screened the deletion lines of bread wheat by western blotting to ascertain common wheat lines lacking the ω-5 gliadin locus. The deletion lines we used have partial deficiency of chromosome 1B (Endo and Gill, 1996). To assess sensitization ability of gluten from the selected deletion line, guinea pigs were fed with either the gluten from the selected deletion line or commercially available gluten, and allergic score was evaluated after challenging the same gluten preparations. RESULTS: We found that a deletion line 1BS-18 had the least deficiency of chromosome 1B among the deletion stocks lacking the ω-5 gliadin locus. The challenge test using the guinea pigs revealed that the symptoms induced by application of the 1BS-18 gluten were much less than that of commercially available gluten. CONCLUSIONS: The deletion line 1BS-18, which lacked the ω-5 gliadin locus, is likely to have a low sensitization capacity in the guinea pig. The use of the wheat products of the 1BS-18 line in daily life may provide a feasible solution for the onset of wheat allergy.

Sodium Cromoglycate Prevents Exacerbation of IgE-Mediated Food-Allergic Reaction Induced by Aspirin in a Rat Model of Egg Allergy.

BACKGROUND: Aspirin (ASP)-facilitated absorption of ingested allergens is considered an exacerbating factor in the development of food allergy. Sodium cromoglycate (SCG) is used for the treatment of atopic dermatitis with food allergy, but the efficacy of SCG in ASP-exacerbated food-allergy reactions is unclear. In this study, we evaluated the effect of SCG on ASP-exacerbated food-allergic reactions, as well as allergen absorption, in egg-allergic model rats. METHODS: Plasma concentrations of ovalbumin (OVA) and fluorescein isothiocyanate-labeled dextran (FD-40), a marker for nonspecific-absorption pathways, were measured after oral administration of mixtures of OVA and FD-40 in OVA-unsensitized and OVA-sensitized rats. IgE-mediated allergic reactions were evaluated by measuring changes in rectal temperature and Evans blue dye (EBD) extravasation in the intestine and liver after oral challenge with OVA. The effects of ASP and SCG on such absorption and allergic reactions were also evaluated kinetically. RESULTS: In OVA-sensitized rats, plasma concentrations of OVA and FD-40 were significantly higher than those in unsensitized rats after oral administration. ASP increased the intestinal absorption of OVA and FD-40 via the paracellular pathway, and a lower rectal temperature and higher EBD extravasation were detected in the intestine and liver of OVA-sensitized rats. SCG ameliorated these ASP-facilitated absorptions and allergic reactions in a dose-dependent manner. In particular, high-dose SCG (195.2 µmol/kg) completely inhibited these absorptions and reactions. CONCLUSION: SCG can prevent ASP-exacerbated allergic reactions in patients with food allergy resulting from inhibition of increases in allergen absorption.

Common food allergens and their IgE-binding epitopes.

Food allergy is an adverse immune response to certain kinds of food. Although any food can cause allergic reactions, chicken egg, cow's milk, wheat, shellfish, fruit, and buckwheat account for 75% of food allergies in Japan. Allergen-specific immunoglobulin E (IgE) antibodies play a pivotal role in the development of food allergy. Recent advances in molecular biological techniques have enabled the efficient analysis of food allergens. As a result, many food allergens have been identified, and their molecular structure and IgE-binding epitopes have also been identified. Studies of allergens have demonstrated that IgE antibodies specific to allergen components and/or the peptide epitopes are good indicators for the identification of patients with food allergy, prediction of clinical severity and development of tolerance. In this review, we summarize our current knowledge regarding the allergens and IgE epitopes in the well-researched allergies to chicken egg, cow's milk, wheat, shrimp, and peanut.