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Biomedical subjects

J M Zubeldia

Publications and source records attributed to J M Zubeldia.

At least 19 recordsLinked to original sources
PubMed2005

Anisakis simplex allergy: a murine model of anaphylaxis induced by parasitic proteins displays a mixed Th1/Th2 pattern.

The study of the singular hypersensitivity reactions to Anisakis simplex (A.s) proteins, may help us to undestand many of the unknown immune interactions between helmiths infections and allergy. We have developed a murine model of allergy to A. simplex, that mimics human A. simplex allergy to study the specific aspects of anaphylaxis induced by parasites. Male C3H/HeJ mice were intraperitoneally sensitized to A. simplex. Mice were then intravenous or orally challenged with A. simplex. Antigen-specific immunoglobulins, polyclonal IgE, anaphylactic symptoms, plasma histamine levels and cytokine profiles were determined. Comparative IgE immunoblot analyses were also performed. Specific IgE, IgG(1) and IgG(2a) were detected in sensitized mice since week 3. Polyclonal IgE raised and peaked with different kinetics. Intravenous A. simplex challenge produced anaphylaxis in mice, accompanied by plasma histamine release. Oral A. simplex challenge in similarly sensitized mice did not caused symptoms nor histamine release. Numerous A. simplex allergens were recognized by sensitized mouse sera, some of them similar to human serum. The A. simplex stimulated splenocytes released IL-10, IFN-gamma, IL-4, IL-13 and IL-5. We describe a new animal model of anaphylaxis. It exhibits characteristics of type I hypersensitivity reactions to Anisakis simplex similar to those observed in allergic humans. Different responses to i.v. or oral A. simplex challenges emerged, which did not reflect a window tolerization period. The cytokine profile developed (mixed Th(1)/Th(2) pattern) differed from the observed in classical models of anaphylaxis or allergy to food antigens. This model may permit to investigate the peculiar allergic reactions to parasitic proteins.

Allergens↗
PubMed2004

Characterization of allergens secreted by Anisakis simplex parasite: clinical relevance in comparison with somatic allergens.

BACKGROUND: Diagnostic methods for the study of allergic reactions to Anisakis simplex (A.s.) based on whole-body extracts of the larva are clearly insufficient. OBJECTIVES: To study the allergenicity of the proteins secreted by the parasite. Comparison with somatic antigens and determination of their clinical importance in allergic patients were also addressed. METHODS: An excretory/secretory (E/S) extract was produced by culturing third-stage A.s. larvae. It was used to perform immediate skin tests and to determine specific IgE in 10 patients diagnosed with allergy to A.s. Both tests were compared with the results obtained with the whole-body extract (somatic (S)). The molecular weight (MW) of their allergens was determined by immunoblotting, and a single-blind placebo-controlled oral challenge with E/S proteins was performed. Finally, allergens' resistance to gastric pepsin and acid pH was explored. RESULTS: A.s. larvae secreted allergens more potent than those present in the S extract. The skin prick test wheal area produced by E/S molecules and the absorbance obtained in the determination of specific IgE with these allergens (ELISA) were 5.8 times bigger than those obtained with S extract. MW allergens of 72 and 56 kDa in E/S extracts and those of 56, 48 and 43 kDa in S extract were recognized by more than 50% of the patients. Partial cross-reactivity between them was revealed by immunoblotting inhibition studies. Oral challenge with E/S extract (up to 479 microg) was negative in all the patients. Treatment of E/S proteins with gastric pepsin inhibited the binding of the E/S allergens for specific IgE. The acid pH did not affect the overall binding of IgE to E/S extract. It decreased by 15.23% and 19.96% at pH 4 and 2, but the difference was not statistically significant. CONCLUSION: A.s. secretes allergens more potent than somatic antigens and should be used in the diagnostic procedures. These allergens are inactivated by the pepsin, which supports the theory that live larva is necessary to induce an allergic reaction in most of the patients.

Adult↗
PubMed2002

Immunostimulatory DNA-based therapeutics for experimental and clinical allergy.

Although allergen immunotherapy (IT) has been shown to modulate allergic hypersensitivities, its efficacy is limited. Recently, in various models of experimental allergy, a number of reagents which we have termed immunostimulatory DNA-based therapeutics have proven highly effective in both the prevention and reversal of Th2 mediated hypersensitivity states. These include immunization with gene vaccines, allergen mixed with immunostimulatory oligodeoxynucleotide (ISS-ODN), and physical allergen: ISS-conjugates (AIC), and immunomodulation with ISS-ODN alone. Results from our laboratory have shown that immunostimulatory DNA-based therapeutics may be effective for the reversal of allergic hypersensitivity states in humans and several clinical trials have already been initiated. This review will focus on our laboratory's experience with immunostimulatory DNA-based therapeutics in various murine models of allergy and their potential utility in the treatment of allergic patients.

Animals↗
PubMed2001

Anisakis simplex-sensitized patients: should fish be excluded from their diet?

BACKGROUND: Anisakis simplex (A.s.) allergy is an emerging disease. The third-stage larvae of this nematode are a source of hidden allergens in fish. There are no clear guidelines concerning dietary restrictions for patients with serum-specific IgE to this parasite. OBJECTIVE: To follow up the clinical data and immunological parameters of patients sensitized to A.s. during 6 to 23 months. METHODS: The clinical symptoms and serologic status of 17 patients with specific IgE and positive skin prick test results to A.s. were studied prospectively. Six of these had anaphylaxis (ANA) attributed to A.s. and 11 patients experienced concomitant chronic urticaria (CU). All patients were advised not to eat fish for 6 months. RESULTS: Four patients from the ANA group excluded fish, and ANA did not recur. Two other patients with ANA refused to exclude fish; one remained free of symptoms and the other experienced several urticarial episodes. During this 6-month period total IgE levels decreased in all six ANA patients; specific IgE for A.s. decreased in four patients and increased in two. Two patients from the CU group did not exclude fish, and symptoms persisted in these two patients. Clinical improvement was observed in 78% of the patients with CU who excluded fish. Total and specific IgE levels decreased in all the patients with CU. CONCLUSIONS: Because ANA symptoms are very severe, patients should always be advised to exclude fish until specific food allergens are identified. However, in patients with CU and specific IgE to A.s., only the clinical response to fish ingestion will determine the need for strict fish avoidance.

Adult↗
PubMed2001

DNA-based immunotherapeutics for the treatment of allergic disease.

Allergic diseases are a growing health concern in industrialized countries. Despite a number of effective therapeutic options for the prevention and treatment of the pathophysiologic responses which characterize allergic diseases, the induction of true allergen desensitization remains an elusive therapeutic goal. Only immunotherapy (IT) has been shown to have any effect on the underlying hypersensitivities which mediate allergic reactions, and traditional protein-based allergen IT has a limited scope of efficacy However, a number of reagents collectively termed DNA-based immunotherapeutics have proven highly effective in both the prevention and reversal of Th2-mediated hypersensitivity states in mouse models of allergic disease. Four basic DNA-based immunotherapeutic modalities have been used for these studies. These include immunization with gene vaccines, allergen mixed with immunostimulatory oligodeoxynucleotide (ISS-ODN), and physical allergen-ISS-ODN conjugates (AIC), as well as immunomodulation with ISS-ODN alone. Results from many laboratories have generated guarded optimism that DNA-based immunotherapeutics may be effective for the reversal of allergic hypersensitivity states in humans, and several clinical trials have already been initiated. This review will focus on our present understanding of the biological activities of DNA-based immunotherapeutics and their application to the treatment of allergic diseases.

Adjuvants, Immunologic↗
PubMed2001

Bezafibrate-induced anaphylactic shock: unusual clinical presentation.

We report a case of a patient who suffered generalized urticaria, chest tightness, wheezing, nausea, vomiting, hypotension, and loss of consciousness. Two hours earlier she had taken Eulitop Retard following lunch. She had tolerated all the implicated food after the reaction. Allergy evaluation revealed intense positive responses to intradermal tests with bezafibrate active component and Eulitop Retard (skin tests in control subjects were negative). Specific IgE tests (RAST) to Eulitop Retard were negative. An IgE mechanism is suggested to be responsible for this adverse reaction on the basis of the positive skin tets. The delayed onset (two hours) of this anaphylactic shock is unusual. Although infrequent, it may be caused by the specific pharmacokinetic characteristics of this drug, which is a slow releasing agent, mainly absorbed in the gut. The drug was taken just after lunch, and this concomitant food ingestion could also have produced a delay in gastric drainage and a retarded drug absorption. An IgE-mediated accelerated type reaction could also explain this delay. Apparently the patient reacted after the first contact to the drug, and the absence of a sensitization period is not usual in this type of immune reponse. Finally, we recommend the performance of prick and intradermal skin tests prior to any systemic challenge when allergic reactions to fibric acid derivatives are suspected.

Anaphylaxis↗
PubMed1999

Allergy to an occupational allergen (Sapelli wood) in a child.

The case is presented of a child who developed rhinoconjunctivitis, angioedema and asthma by sensitization to Sapelli wood, which was used in his father's carpentry. Positive skin-prick test, high levels of specific immunoglobulin E by ELISA and a positive conjunctival challenge test suggest a type I hypersensitivity mechanism to this wood. This is the first case report of sensitization to Sapelli wood and it confirms that occupational allergen exposure as Sapelli wood may also cause sensitization in a child.

Allergens↗
PubMed1998

Fluorescein-induced allergic reaction.

BACKGROUND: Adverse reactions following intravenous sodium fluorescein are very unusual and their mechanism is still uncertain. We report the case of a patient who suffered an adverse reaction during a fluorescein ocular angiography. Positive allergy tests to fluorescein suggest an IgE-mediated mechanism. OBJECTIVE: Report the allergy evaluation performed in a patient who suffered an adverse reaction during an intravenous fluorescein administration. METHODS: We selected the case of a patient who suffered dizziness, diaphoresis, generalized pallor, nausea, sphincter relaxation, hypotension, and intense malaise during a fluorescein ocular angiography and compared the results to other nonreactive subjects. Allergy evaluation: Prick and intradermal skin tests and serial determinations of serum tryptase were performed on the patient and four control subjects who underwent and tolerated the same procedure as well as on a patient who developed an intense vagal reaction during blood extraction. RESULTS: Positive skin tests and dramatic increase of serum tryptase (67U/I) were observed in our patient. The rest of the patients had negative skin tests and did not have any variation in their serum tryptase. CONCLUSIONS: An IgE-mediated mechanism is suggested as responsible for this adverse reaction. We recommend that a complete allergy evaluation should be performed in all patients who have adverse reactions to fluorescein in order to differentiate true allergic reactions from other types of reactions.

Aged↗
PubMed1997

Serum tryptase levels in adverse drug reactions.

We evaluated the usefulness of individual tryptase levels and variations after adverse drug reactions in 64 patients. Our aim was to find a tool for the diagnosis of drug allergy. Thirty-seven subjects were confirmed to have drug allergy, 12 had nonsteroidal anti-inflammatory drug (NSAID) reactions, five had negative controlled drug challenges (NAAR), and 10 had symptoms after placebo intake (PLA). Serum tryptase levels greatly increased after anaphylactic shocks (2242%) and anaphylaxis (710.5%). Patients with allergic urticaria and those with idiosyncratic responses to acetylsalicylic acid (ASA) exhibited a small increase in serum tryptase (49.5% and 38.2%, respectively). In the other two groups (NAAR and PLA), no variation in this serum protease was observed. The time of appearance of the serum tryptase peak differed considerably among patients with similar clinical reactions (from 30 min to 6 h) and was independent of the latent period, severity of symptoms, or the amount of tryptase released. We conclude that serum tryptase determinations are helpful in the diagnosis of anaphylactic shock and anaphylaxis, but serial measurements may be needed to confirm mast-cell participation in milder reactions.

Anaphylaxis↗
PubMed1990

Murine eosinophils and IL-1: alpha IL-1 mRNA detection by in situ hybridization. Production and release of IL-1 from peritoneal eosinophils.

The presence of IL-1 mRNA in eosinophils from mice infected with larvae of the parasite Mesocestoides corti was investigated by in situ hybridization technique. S35 labeled cDNA probe for alpha IL-1, hybridized with mRNA in murine eosinophils and macrophages. After 6 h of LPS stimulation eosinophils were able to express mRNA in their cytoplasm. This expression was highly increased by the addition of indomethacine. The IL-1 mRNA expression in murine macrophages was higher than in eosinophils in LPS-stimulated cells. This difference was statistically significant, p less than 0.001. To test if eosinophils may produce and release IL-1 in the culture medium, we isolated these cells in a Percoll gradient. Cell preparations with a purity exceeding 94% were cultured with various stimuli and their supernatants were tested for IL-1 activity. Eosinophils produced 169.65 +/- 73 U/ml when stimulated with LPS (n = 14). A dose-dependent response was obtained when the eosinophils were in the presence of the calcium ionophore A23187. Controls were performed to rule out the contribution of the contaminating population on the thymocyte proliferating activity. They were also used to detect other possible causes of interference in the assay, such as leukotrienes or TNF. IL-1 in supernatants was also detected using a conversion assay such as EL-4 thymoma cells. IL-1 activity was first detected in culture supernatants 18 h later, maximal production being in the first 24 h. In accordance with our hybridization results, an increase in IL-1 activity was obtained when eosinophils were stimulated with LPS and treated with indomethacine. The factor had a molecular mass between 16 to 20 kDa that corresponded to the described for murine IL-1. Inasmuch as IL-1 is an important mediator of inflammatory reactions this IL may enhance the proinflammatory action of eosinophils.

Animals↗
PubMedDate not supplied

Dietary recommendations for patients allergic to Anisakis simplex.

BACKGROUND: Anisakis simplex, a fish parasite, causes allergic urticaria, angioedema and anaphylactic shock through an IgE-mediated hypersensitivity mechanism. Consensus on the dietary recommendations that should be given to allergic patients is lacking. Our objective was to evaluate the usefulness of different types of diets in preventing further reactions in patients allergic to A. simplex. METHODS: Twenty-eight adult patients, who had suffered an allergic episode caused by A. simplex were asked to follow one of the following three diets for a mean period of 13.16 months: a fish-free diet (diet 1; n = 19), a diet including fish frozen for more than 48 hours (diet 2; n = 9) and a diet with fresh fish (diet 3; n = 12). In all patients raw fish was excluded. Relapse rates and changes in total serum IgE and specific IgE to A. simplex were studied during the follow up. RESULTS: During the 13-month follow-up none of the patients developed anaphylaxis. Urticaria symptoms were present in 5.8 %, 11.1 % (n.s) and 33.3 % (p = 0.016) of patients following diets 1, 2 and 3, respectively. Total IgE decreased by 64 % (p < 0.05), 48 % (p < 0.05) and 39.4 % (p < 0.05), respectively. Specific IgE to A. simplex decreased by 50.7 % (p < 0.05), 54.1 % (p < 0.05) and 23.6 % (p < 0.05) after diets 1, 2 and 3, respectively. No statistically significant differences were found among the groups in variations in total and specific IgE. CONCLUSIONS: Patients allergic to A. simplex can eat fish that has been frozen at -20 C for 48 hours without risk of a severe allergic reaction. Long term decreases in specific and total IgE may not be good markers of eventual contact with A. simplex.

Adult↗
PubMedDate not supplied

Is Anisakis simplex responsible for chronic urticaria?

The association of chronic urticaria (CU) to parasitic infestations has been poorly studied. Recently, sensitization to the parasite larva Anisakis simplex has been described as the cause of acute urticaria and anaphylaxis. The aim of this work was to study the relationship between sensitization to A. simplex and CU. One hundred one patients with CU were studied. Data of possible contacts with A. simplex were collected and the usual CU study was performed. Furthermore, total and specific immunoglobulin E (IgE; Pharmacia CAP system IGE fluorescence enzyme immunoassay: CAP) to A. simplex, Ascaris lumbricoides, Echinococcus granulosus, and Toxocara canis were determined as well as skin-prick test with A. simplex and serology to E. granulosus. In accordance with the results of the CAP to A. simplex, the patients were divided into two groups, positive and negative, and, subsequently, subdivided into two other subgroups that were alternatively told to stop eating fish or seafood in their diet or to continue with their normal diet. Checkups were performed at 6, 12, and 18 months. Thirty-five percent of the patients had positive skin tests to A. simplex, and CAP to A. simplex was positive in 55%. The fish-eating habits, acute or chronic gastrointestinal disease, and the background of abdominal surgery were not related to the results of the CAP and/or skin test to A. simplex. A total of 21.8% of all the patients had detectable CAP to A. lumbricoides, 91% of whom had positive CAP to A. simplex. Three patients had specific IgE to T. canis and five patients had specific IgE to E. granulosus, in the absence of positive serology. All had specific IgE to A. simplex. Present infestation could not be proved in any of them. The clinical evolution and variations of CAP to A. simplex and of total IgE were not statistically different among the groups during the 6, 12, and 18 months of the study. The percentage of sensitization to A. simplex in patients with CU is elevated and determines the sensitization to other parasites because of cross-reactivity. We have not found any causal relationship between the presence of specific IgE to A. simplex and CU. The clinical importance of this finding in this disease is still undetermined.

Adolescent↗
PubMedDate not supplied

Recurrent fixed drug eruption caused by citiolone.

Citiolone (N-acetylhomocysteinethiolactone) is a thiolic-derived medication frequently used in Spain and in other countries as a mucolytic agent for the treatment of certain hepatic disorders. Mucolytic drugs have rarely been implicated in the fixed drug eruption etiology. We report on a patient who presented several episodes of fixed exanthema related to citiolone intake. The patch test with citiolone (10% in dimethyl sulfoxide) was negative. The diagnosis was confirmed by a positive controlled oral challenge test. Other mucolytic thiolic-derivatives (N-acetylcysteine) were tolerated by the patient, thus crossreactivity between these drugs seems to be unlikely.

Acetylcysteine↗