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Biomedical subjects

G Mistrello

Publications and source records attributed to G Mistrello.

At least 55 records · Page 3Linked to original sources
PubMed1997

Pharmacokinetics of allergens after local administration.

The authors review the status of knowledge on absorption and kinetic of allergens administered on nasal mucosa. Intranasal administration is well known in pharmacology, and has been used for a long time for peptide drugs, mainly hormones. The immunological response to intranasally administered antigens have been studied in some experimental models: bovine Rnase, dextran, KLH, tetanus toxoid. These studies showed in atopic people a greater absorption of antigens by nasal mucosa compared to normal individuals, a difference that might be of importance in the pathogenesis of atopic diseases. The absorption rate of peptides through nasal mucosa has been studied biologically by PK-test with Rnase and peanut allergen, and a consistent passage of intact molecules has been observed. Using as tracer 125I-labelled human albumin, transport across the nasal mucosa has been demonstrated in 3/9 normal subjects, 1/9 patients with extrinsic asthma and 9/10 patients with atopic rhinitis. In experimental animals (rabbits) the passage of allergens through the nasal mucosa has been confirmed using 125I-labelled Parietaria allergens that showed a peak in the bloodstream 60 min after administration. It is concluded that peptide molecules such as allergens can be absorbed through the nasal mucosa and reach the bloodstream, and that in atopic patients nasal permeability is enhanced.

Administration, Intranasal↗
PubMed1996

Comparison between outdoor and indoor airborne allergenic activity.

BACKGROUND: Allergenic pollens are usually detected in outdoor air by using volumetric spore traps, which allow measurement of atmospheric concentration as pollen grains per m3 of air. The results of the pollen count are useful primarily for outdoor environments while most people spend most of the day indoors. OBJECTIVE: The purpose of our study was to compare outdoor pollen levels with allergenic activity measured both outdoors and indoors. METHODS: We used a Lanzoni spore trap to measure airborne Urticaceae pollen and filters collecting particles simultaneously indoors and outdoors and assayed each filter for Parietaria judaica allergenic activity. Samples were collected at the Allergological Service of the "A. Cardarelli" Hospital in Naples with the balcony open on some days and closed on others. Allergenic activity (ng/m3) was measured using the immunocapture RAST. RESULTS: With the balcony open there was no great difference between outdoor and indoor allergenic activity, but with the balcony closed there was a reduction of indoor allergenic activity of about one-third in comparison with outdoor allergenic activity. Statistical analysis (Pearson correlation test) indicated a significant correlation between outdoor allergen levels and indoor allergen levels with the balcony open (r = .4415, P < .05), but not with the balcony closed (r = .3160, P > .05); a significant correlation between outdoor pollen count and indoor allergen levels with the balcony open (r = .4809, P < .05), but not with the balcony closed (r = .3858, P > .05); and a highly significant correlation (r = .5225, P < .001) between outdoor pollen count and outdoor allergen levels. CONCLUSIONS: These data provide scientific evidence for the recommendation to hay fever patients to remain indoors during seasons with high levels of outdoor pollens.

Air Pollutants↗
PubMed1996

Oral allergy syndrome (OAS) in pollinosis patients after eating pistachio nuts: two cases with two different patterns of onset.

We describe two uncommon cases of oral allergy syndrome (OAS) after eating pistachio nuts (p.n.) in subjects (a 54-year-old man and a 3-year-old girl) with exclusive skin prick test (SPT) positivity to Parietaria (P.) and pistachio nut (p.n.) allergens. Serologic P.- and p.n.-specific IgE determinations were also carried out. A double-blind, placebo-controlled food challenge (DBPCFC) was performed, for ethical reasons, only in the adult patient, but we observed a positive intraoral reaction only after slight scratching of the oral mucosa. Since this patient had put three whole p.n. with their shells into his mouth, breaking them with his teeth, before the onset of symptoms, we suggest that slight injury of the oral mucosa may enhance the local response. Preliminary results with SDS-PAGE and immunoblotting demonstrate the occurrence of a slight degree of cross-reactivity between these allergens, but further studies are necessary to obtain a definite conclusion.

Child, Preschool↗
PubMed1996

Monomeric chemically modified allergens: immunologic and physicochemical characterization.

Allergenic extracts (Der p, grass, and Parietaria) or single allergens such as Par j I (the major allergen of Parietaria) and ovalbumin (OA), a food allergen widely used in animal models, were chemically modified by reaction with potassium cyanate (KCNO), which transforms the epsilon-amino group of the lysine of proteinaceous allergens into ureido groups. KCNO-modified (carbamylated) allergens have low allergenic potency, as demonstrated in vitro (RAST inhibition) and in vivo (passive cutaneous anaphylaxis). When used to immunize rabbits, carbamylated allergens still induce IgG antibodies able to cross-react with native allergens (immunoblotting experiments). An interesting feature distinguishing carbamylated allergens from other chemically modified allergens is the preservation of the native monomeric dimension as demonstrated by SDS-PAGE analysis. Results are discussed from the perspective of clinical application of carbamylated allergens.

Allergens↗
PubMed1994

Evaluation of allergenic potency by REAST inhibition. A new tool for the standardization of allergenic extracts.

The potency of allergenic extracts can be determined in vitro by RAST inhibition, and this has become the preferred method for the standardization of allergens. A disadvantage of this technique is the impossibility of obtaining data about allergens bound to the solid phase, i.e., the counterpart of the inhibiting extract. The REAST (reverse enzyme allergosorbent test) is based on the capture of IgE by a specific antibody bound to microtiter wells, the reaction of captured IgE with biotinylated allergen and the development of a colour reaction by subsequent addition of streptavidin-peroxidase and chromogenic substrate. The addition of an allergen extract in a dose-response fashion competes with the biotinylated allergen and inhibits the test. In the present study REAST inhibition has been evaluated with Dermatophagoides pteronyssinus, Parietaria judaica and mixed grass pollen extracts. The correlation of REAST inhibition with RAST inhibition and both intra-assay and inter-assay reproducibility have been evaluated. REAST inhibition is a potentially valuable new tool for the standardization of allergenic extracts.

Allergens↗
PubMed1994

cDNA cloning, expression and primary structure of Par jI, a major allergen of Parietaria judaica pollen.

A 659 bp cDNA clone** coding for an allergen of Pj pollen has been isolated from a lambda gt11 library, and its DNA sequence determined. The cDNA insert showed an open reading frame of 429 bp coding for an allergenic protein of 14,866 Da and a deduced amino acid sequence containing 143 residues. The expressed recombinant protein represented the major allergen Par jI since it reacted with 95% of the sera from Pj-allergic patients (n = 22) and with two Par jI-specific monoclonal antibodies. No similarity with other known DNA and protein sequences has been detected.

Allergens↗
PubMed1994

Modified par j I allergen from P judaica pollen and its rate of absorption in rats.

Polymerized allergens (allergoids) have been introduced in the immunotherapy of allergic disease in order to reduce the risk of side effects. However, their high molecular weight can be a limit, particularly when they are administered by a route involving passage through the mucosal barrier. We describe a simple procedure aimed at developing an original modified allergen with significantly less allergenic potential (intended as human IgE-binding capacity) but preserving the monomeric nature of the molecule. Par j I, the major allergen of Parietaria judaica pollen, was purified by a combination of monoclonal antibodies and affinity chromatography. Par j I allergen was then modified by reaction with potassium cyanate (KCNO), and compared with the native allergen to evaluate its allergenic potency (RAST-inhibition) and molecular weight (SDS-PAGE). Modified allergen showed significantly lower allergenic potency but kept its original molecular weight, making it particularly suitable for buccal (sublingual) administration. To study the adsorption profile, modified Par j I was radiolabeled and administered intravenously and sublingually to normal rats. The prospects for clinical application of the modified allergen are discussed.

Absorption↗
PubMed1994

Detection of Parietaria judaica airborne allergenic activity: comparison between immunochemical and morphological methods including clinical evaluation.

Airborne pollen grains and small plant particles of respirable size are the main causes of rhinitis and asthma in pollinosis patients. Consequently, it could be useful to quantify atmospheric variations in these biological aerosols and their allergenic activity as a basis for establishing correlations with the clinical symptoms in these allergic subjects. Our study was conducted in Naples from May to August 1992 and from May to August 1993 and concentrated on Parietaria judaica (Par j) the most important hay fever-provoking plant in southern Italy. The aim of this study was to evaluate the day-to-day variation in counts of Par j. pollen, the day-to-day variation in allergenic activity specific for this plant, and to relate these two variables to symptom scores in patients with respiratory allergy to Par j. The airborne pollen grains were collected by a Hirst-like volumetric trap and examined through an optical microscope, while the allergenic activity of particles trapped on glass fibre filters in a high volume air-sampler was determined by immunochemical assay. The two devices were placed on the flat roof of the 'A. Cardarelli' Hospital. The results of this preliminary study suggest that both methods could have useful clinical relevance, since these two biological parameters were significantly correlated with the symptom scores of allergic patients. However, pollen count with morphological quantification of grains/m3 of air is a more simple technique.

Allergens↗
PubMed1991

Allergenic fragments in Parietaria judaica pollen extract.

High-performance ion-exchange chromatography and immunoaffinity chromatography suggest that Par jI, the principal allergenic component of Parietaria judaica pollen, is a very unstable molecule, which tends to fragment in solution. Several fragments were obtained from Par jI and some of them show positivity toward the anti-Par jI monoclonal antibody, suggesting that they retain the entire structure of the allergenic determinant. These fragments could be the target for sequence and conformation studies.

Allergens↗
PubMed1991

Detection of IgE-binding activity in serum after intranasal treatment of normal rabbits with P. judaica extract.

Local intranasal immunotherapy relieves the allergic symptoms of rhinitic patients but little is known about the absorption and distribution of inhaled allergens in the body. The aim of this study was to establish whether allergenic proteins are able to reach the bloodstream by penetrating through the nasal mucosa when aqueous P. judaica extract was administered into the nostrils of normal rabbits. Optimal conditions for a sensitive modified RAST (immunocapture RAST) were set up and the method was used to detect clinically relevant allergenic activity in the systemic circulation. The kinetic profile after intranasal treatment was compared with the profile after intravenous injection of the allergenic extract. The findings are discussed in relation to the mechanism by which local immunotherapy acts.

Administration, Intranasal↗
PubMed1991

Inhaled furosemide prevents both the bronchoconstriction and the increase in neutrophil chemotactic activity induced by ultrasonic "fog" of distilled water in asthmatics.

Inhaled furosemide has been shown to prevent bronchoconstriction induced by inhalation of ultrasonic nebulization of distilled water (UNDW) in bronchial asthma. To evaluate whether inhaled furosemide also prevents the increase in serum neutrophil chemotactic activity (NCA) observed during UNDW bronchoconstriction, we measured NCA during UNDW challenge without (control) and immediately after inhalation of furosemide (40 mg) or placebo (saline) in 10 asthmatics responsive to UNDW, in a randomized, double-blind study. NCA was assessed by measuring the maximal distance reached by neutrophils in a filter when challenged with the subject serum in a Boyden chamber ("leading front"). UNDW inhalation produced a significant increase in NCA in each subject. Gel filtration chromatography on S400 column indicated that the NCA released were 600 to 700 kD. Saline had no effect on bronchoconstriction nor on NCA increase induced by UNDW in nine patients. Furosemide did not change baseline FEV1, but it prevented bronchoconstriction and NCA increase in nine patients. In the whole group the maximal decrease in FEV1 after UNDW was -31.1%, SEM 4.7 after saline and -7.5%, SEM 5.2 after furosemide, p less than 0.001, the maximal increase in NCA after UNDW was +52.9%, SEM 9.2 after saline and +3.8%, SEM 3.1 after furosemide, p = 0.001. These results indicate that inhaled furosemide prevents both the bronchoconstriction and the NCA increase induced by UNDW inhalation in most asthmatic patients. This finding adds support to the suggestion that furosemide acts on mast cells.

Administration, Inhalation↗
PubMed1985

Contragestational profile of the tumor-inhibiting agent, L-alanosine, in the rat and the hamster.

L-Alanosine [L-2-amino-3(N-hydroxy-N-nitrosamino)propionic acid], a tumor-inhibiting agent, induces pregnancy arrest after single or multiple SC or PO administration to rats and hamsters. Its contragestational effects are dose- and route-dependent, with no important differences in species-sensitivity or administration schedules. L-Alanosine is maximally effective shortly (3-4 days) after implantation. Both placenta and fetus appear to be target tissues. Consistent with previous in vitro findings, adenine but not aspartic acid counteracts the contragestational action of L-alanosine. The 'contragestational test', i.e., the effect on conceptus growth, appears to be an interesting approach for learning more about the antiproliferative activity of an antineoplastic agent.

Adenine↗
PubMed1985

Immunological profile of DL111-IT, a new immunosuppressant agent.

The immunosuppressive properties of the non-hormonal contragestional agent 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole (DL111-IT) were evaluated on different immunological functions. The compound displayed significant immunosuppressive activity on both humoral and cellular immunity when administered during the inductive phase of the immune response. In experimental models autoimmunity and skin transplantation, DL111-IT was able to reduce the production of auto-antibodies and prolong skin graft survival. The compound, even at doses much higher than those effective inhibiting immune responses, did not influence the survival time of some haematological tumors in mice. This suggest that DL111-IT does not act by a general cytotoxic mechanism.

Animals↗
PubMed1984

Effect of L-alanosine on immune response.

L-alanosine is an antitumor compound which has recently entered clinical trials. Single i.p. doses of this drug inhibit antibody production to thymus-dependent and thymus-independent antigens as well as delayed hypersensitivity to SRBC in mice. Moreover, the in vitro lymphoproliferative responses of splenocytes to Concanavalin A and bacterial Lipopolysaccharides are also affected when the drug is added upon setting up the cultures. On the other hand, in vivo treatment with L-alanosine does not impair spleen natural killer (NK) activity. The results are discussed in an effort to characterize the immuno-suppressive activity of L-alanosine.

Alanine↗