muramidase and Drug-Hypersensitivity

The Drug Allergy Committee of the Spanish Society of Allergology and Clinical Immunology reviewed the allergenic potential of several substances of food origin that are found in the composition of some drugs. Despite recent legislation on labeling, many labels do not clearly state whether the drug contains raw material (active ingredients, excipient, or other manufacturing intermediate) with an origin in any of the substances in the list of the 14 groups of food allergens that are subject to mandatory declaration. The objective of legislation is that the drug package, the Summary of Product Characteristics, and the patient information leaflet clearly state the food content in order to improve the safety of allergic patients. Therefore, any food or allergen derivative that must be declared should be clearly stated on the drug label. Of all the evaluated products, egg and milk derivatives are the most frequently discussed in literature reviews. The natural or synthetic origin of potentially allergenic substances such as lysozyme, casein, lactose, albumin, phosphatide, and aromatic essences should be clearly stated. Providing this information has 2 clear advantages. First, allergic reactions to drugs in patients with food allergy could be avoided (if the substances have a natural origin). Second, prescription would improve by not restricting drugs containing synthetic substances (which do not usually induce allergic reactions).

Topics: Drug Hypersensitivity; Food Additives; Food Hypersensitivity; Glucosamine; Humans; Lactose; Muramidase; Ovalbumin; Propofol; Spain

Topics: Blood Cells; Cholinesterase Inhibitors; Contrast Media; Drug Hypersensitivity; Glucuronidase; Humans; Hypertonic Solutions; Muramidase; Nervous System Diseases; Protein Binding; Serum Albumin; Vascular Diseases; Water-Electrolyte Balance

This paper reports the case of an egg-allergic pediatric patient who, once desensitized to egg following a successful rush oral immunotherapy protocol, could also tolerate Lizipaina®, a drug containing lysozyme (LYS) and papain, which had previously caused him a severe allergic reaction. Because the LYS amount that elicited the anaphylactic reaction (5 mg) was much lower than that tolerated during a double-blind placebo-controlled food challenge (corresponding to approximately 60 mg of LYS), the possibility that the presence of papain could increase the allergenic potential of LYS was investigated.. Lizipaina, LYS and LYS hydrolyzed with papain were analyzed by SDS-PAGE under reducing and nonreducing conditions, and Western blotting of sera from egg-allergic patients was performed in order to detect IgE-binding fragments. Finally, sequence identification of the IgE-reactive bands was carried out by MALDI-TOF/TOF.. The SDS-PAGE pattern of LYS treated with papain under nonreducing conditions showed the presence of intact LYS that partially disappeared following reduction with β-mercaptoethanol, releasing IgE-reactive fragments as determined by Western blotting. MALDI-TOF/TOF revealed that papain degraded LYS, giving rise to three IgE-binding fragments: LYS (22-129), LYS (34-96) and LYS (62-128) that likely remained linked through the disulfide bonds present in the LYS molecule.. The combined administration of LYS with proteolytic enzymes such as papain may have developed a severe allergic reaction in the patient studied, underlining the importance of considering all the components and their interactions when drugs are to be consumed by allergic persons.

Topics: Adolescent; Amino Acid Sequence; Anaphylaxis; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Egg Hypersensitivity; Humans; Immunoglobulin E; Male; Molecular Sequence Data; Muramidase; Papain; Peptide Fragments

Topics: Dermatitis, Atopic; Drug Hypersensitivity; Egg Hypersensitivity; Humans; Immunoglobulin E; Infant; Male; Muramidase; Nasal Decongestants

Seven patients who received a lysozyme, nystatin, and tetracycline containing vaginal suppository because of suspected vaginal infection, developed local or systemic allergic reactions. The coincidence of the symptoms with the repeated use of the suppository as well as skin and lymphocyte transformation tests indicated that the lysozyme in the suppository was responsible for the allergic reactions. This lysozyme preparation contained additional egg proteins, which contributed to the allergic reaction in certain patients: three patients with a previous history of egg allergy and serologic and/or skin test evidence for egg-white sensitization developed the allergic reaction after the first suppository. Four patients had urticaria or anaphylaxis after treatment for at least three days; none of these four patients developed egg allergy. Five of seven individuals had positive skin tests (prick or scratch) to ovomucoid and lysozyme, but none of the patients had lysozyme-specific IgE in the circulation. All seven patients, with or without egg allergy, showed vigorous T cell responses to purified lysozyme and partly to other egg-white proteins in the lymphocyte transformation test, which was absent in controls. Vaginal suppositories that contain lysozyme and other contaminating egg white proteins can either elicit allergic reactions in patients with a preexisting egg white allergy or induce sensitization to lysozyme and other egg white components.

Topics: Adult; Antibody Specificity; Drug Hypersensitivity; Egg White; Female; Humans; Immunoglobulin E; Lymphocyte Activation; Middle Aged; Muramidase; Skin Tests; Suppositories; Vagina

Foreign-body (dextran beads) and hypersensitivity (antigen-coupled agarose beads) lung granulomas were induced in BALB/c mice by the intratracheal injection of beads. Large granulomas developed, which reached peak intensity within 3 days and declined in size thereafter. Aqueous extracts of both granulomas contained high levels of lysosomal enzymes N-acetyl-beta-D-glucosaminidase (NAG) and lysozyme. Lysosomal enzyme activities in the extracts correlated with granuloma sizes. Dispersed granuloma cells were able to produce these enzymes. These results suggest that lysosomal enzymes may reflect the activity/size of granulomatous inflammation.

Topics: Acetylglucosaminidase; Analysis of Variance; Animals; Dextrans; Drug Hypersensitivity; Granuloma; Lung Diseases; Lysosomes; Mice; Mice, Inbred BALB C; Muramidase; Time Factors

The effect of cyclosporin A (CsA) on suppressor T cells (Ts) was evaluated by in vitro incubation with afferent-phase Ts (Ts-aff) and efferent-phase Ts (Ts-eff). 2,4-Dinitro-1-fluorobenzene (DNFB) and hen egg-white lysozyme (HEL) were used as antigens. Both Ts-aff and Ts-eff were resistant to high- and low-dose CsA treatments. However, T cells associated with delayed type hypersensitivity (DTH) [TDTH] to DNFB or HEL were sensitive to these CsA treatments. These results indicate that the effect of CsA treatment on contact sensitivity and DTH influences TDTH and not Ts.

Topics: Animals; Cyclosporins; Dinitrofluorobenzene; Dose-Response Relationship, Drug; Drug Hypersensitivity; Female; Hypersensitivity, Delayed; Mice; Muramidase; T-Lymphocytes, Regulatory

To shed more light on the immunopathogenesis of drug-induced acute interstitial nephritis, a combined histologic, immunopathologic, and ultrastructural study of renal biopsy specimens from nine patients with drug-induced renal disease was performed. None of the patients had pre-existing renal disease or evidence of sarcoidosis or tuberculosis. The principal drugs included a hydrochlorothiazide-triamterene combination (Dyazide), hydrochlorothiazide, fenoprofen, and furosemide and triamterene. Renal insufficiency developed approximately four to ten weeks after initiation of drug therapy. In all cases, withdrawal of the drug(s) with or without steroid therapy resulted in restoration of normal or near-normal renal function. Histologically, all biopsy specimens showed acute interstitial nephritis characterized by an intense but patchy mononuclear cell interstitial infiltrate consisting of lymphocytes, monocytes, and plasma cells, modest numbers of eosinophils, patchy tubular atrophy, interstitial edema, and normal glomeruli. All biopsy specimens contained interstitial (and, in two cases, perivascular) non-caseating granulomas, which were numerous in one case, moderate in four cases, and rare in the remainder. Direct immunofluorescence was negative for IgG, IgM, IgA, C1q, C4, and C3 along glomerular and tubular basement membranes. Immunoperoxidase staining for lysozyme (performed in three cases) demonstrated many positive cells in the infiltrate. In two cases in which granulomas were present in prepared sections, the epithelioid and multinucleated giant cells did not stain for lysozyme. Electron microscopy of the granulomas in two cases revealed that the epithelioid and giant cells had "secretory" features characteristic of hypersensitivity granulomas. These findings provide further evidence for the participation of cell-mediated immunity in the pathogenesis of at least some cases of drug-induced acute interstitial nephritis.

Topics: Adult; Aged; Drug Hypersensitivity; Female; Fenoprofen; Fluorescent Antibody Technique; Furosemide; Granuloma; Humans; Hydrochlorothiazide; Hypersensitivity, Delayed; Immunity, Cellular; Immunoenzyme Techniques; Immunoglobulin E; Kidney; Macrophages; Male; Middle Aged; Monocytes; Muramidase; Nephritis, Interstitial; Triamterene

The mode of reaction of benzylpenicillin with two proteins was studied, with particular reference to the allergenicity of penicillin. These reactions, with pig insulin, and with hen's-egg-white lysozyme, were carried out in neutral solution at 37 degrees C. High concentrations of penicillin are needed to label the proteins, owing to concurrent hydrolysis of penicillin. Evidence has been obtained that the penicillin-reactive sites on the insulin molecule are the alpha-amino group at the N-terminus of the A chain and the epsilon-amino group of the lysine residue; whereas a site of reaction with lysozyme appears to be the epsilon-amino group of lysine-116.

Topics: Amino Acids; Animals; Binding Sites; Chickens; Drug Hypersensitivity; Egg White; Humans; Insulin; Kinetics; Muramidase; Penicillin G; Peptide Fragments; Protein Binding; Swine

1. Rats genetically resistant to dextran and other agents producing the anaphylactoid reaction (NR rats), have a higher polymorph count than do rats which react to these agents (R rats).2. NR rats do not develop polyarthritis when a hind paw is injected intradermally with Freund's adjuvant.3. The polyarthritis produced by an intravenous injection of Mycoplasma arthritidis culture develops more slowly in NR rats than in R rats.4. It is not clear whether the higher polymorph count in NR rats is a main factor in determining their resistance to adjuvant-induced arthritis.

Topics: Animals; Arthritis; Complement System Proteins; Dextrans; Drug Hypersensitivity; Freund's Adjuvant; Hematocrit; Horses; Leukocyte Count; Male; Muramidase; Mycoplasma; Rats; Rats, Inbred Strains

Topics: Adult; Anti-Bacterial Agents; Ascorbic Acid; Brucellosis; Chronic Disease; Drug Hypersensitivity; Female; Humans; Immunotherapy; Male; Middle Aged; Muramidase; Oleandomycin; Phagocytosis; Physical Therapy Modalities; Pigments, Biological; Prodigiosin; Pyrroles; Serratia marcescens; Stimulation, Chemical; Tetracycline; Vitamins

Topics: Animals; Antibody Formation; Antibody Specificity; Antigen-Antibody Reactions; Antigens; Carbon Isotopes; Chemical Phenomena; Chemistry; Chromatography, Ion Exchange; Dermatitis, Contact; Drug Hypersensitivity; Formaldehyde; Goats; Haptens; Hypersensitivity, Delayed; Immunodiffusion; Immunoelectrophoresis; Muramidase; Ovalbumin; Rabbits; Serum Albumin

Topics: Animals; Antigens; Chickens; Collagen; Drug Hypersensitivity; Guinea Pigs; Humans; Muramidase; Penicillins; Rabbits; Skin Tests; Tuberculin

Topics: Adolescent; Chronic Disease; Drug Hypersensitivity; Humans; Male; Muramidase; Sinusitis

Topics: Drug Hypersensitivity; False Positive Reactions; Heparin; Histones; Hyaluronoglucosaminidase; In Vitro Techniques; Indicators and Reagents; Mast Cells; Muramidase; Neomycin; Polymyxins; Protamines