Studies on experimental iodine allergy: 3. Low molecular weight elicitogenic antigens of iodine allergy.

We hypothesize that iodine allergy is an immune response to iodinated self proteins produced in vivo from various iodine-containing chemicals. Since an antigenic determinant of experimental iodine allergy is diiodotyrosine (DIT), we designed low molecular weight DIT derivatives having provocative antigenicity without sensitizing immunogenicity. Tetraiododityrosine and hexaiodotrityrosine provoked dose-dependent skin reactions in guinea pigs previously immunized with iodine. No guinea pigs immunized with hexaiodotrityrosine showed anaphylactic reaction by i.v. challenge with hexaiodotrityrosine and none of their antisera showed positive passive cutaneous anaphylaxis (PCA) reaction in guinea pigs, indicating the non-immunogenic nature of the compound. Erythrosine, one of the color additives having a structure common with DIT, was assessed for its immunological property. Enzyme-linked immunosorbent assay (ELISA) inhibition studies on erythrosine revealed that the inhibitory activity of erythrosine was stronger than that of DIT. Furthermore, erythrosine provoked a PCA reaction in animals sensitized with anti-iodine antisera. In conclusion, hexaiodotrityrosine is thought to be useful for skin testing of iodine allergy without any fear of sensitization to the allergen. Erythrosine was shown to provoke an experimental iodine allergy and, also, the relationships between the new concept of iodine allergy and features of clinical findings of adverse effects by iodocontrast media are discussed.

Di-iodo-L-tyrosine-labelled dextrans as molecular size markers of nasal absorption in the rat.

A series of fractionated di-iodo-L-tyrosine-labelled dextrans (DIT dextrans), with a narrow range of number average molecular weights from 1260 to 45,500 Da, was administered intranasally and intravenously to anaesthetized rats. The nasal absorption of these compounds ranged from 0.6 to 52.7%. There was an inverse relationship between molecular size and the proportion of an intranasal dose absorbed. The study demonstrated the usefulness of DIT dextrans as molecular weight markers and confirmed the relationship between molecular size and nasal absorption for highly water soluble compounds. These results also supported the proposition that there is a continuous range of aqueous pores in the nasal mucosa.

[Biological value of the meat from animals implanted with betazine and diiodotyrosine and its effect on the body]. / Biologicheskaia tsennost' miasa zhivotnykh, implantirovannykh betazinom i diiodtirozinom, i ego vliianie na organizm.

The biological value of beef and pork of the animals implanted with antithyroid preparations did not differ from that of controls in varying tests. A long-term feeding of rats with diets containing meat of young bulls and pigs, implanted with betazine and diiodotyrosine, did not influence the content of free and bound cholesterol and total phospholipids in the liver, and produced no effect on the intensity of oxidative phosphorylation in the mitochondria which was proved by the results of the morphological, histochemical and ultrastructural investigations.

IgG purification to measure the level of an iodinated thyroglobulin peptide, the 3,5,3',5' tetraiodo-l-tyrosyl-l-tyrosine in human serum.

Antibodies reacting with 3,5,3',5' tetraiodo-l-tyrosyl-l-tyrosine (I2Tyr-I2Tyr) were elicited in rabbits by immunization with an oxidized yeast conjugate coupled with I2Tyr-I2Tyr. Ion-exchange chromatography was used to purify immunoglobulins, in order to improve the specificity in measurement of I2Tyr-I2Tyr level in patient serum. IgG binding capacity versus I2Tyr-I2Tyr was considerably increased after immunoglobulin purification.

[Ultrastructural changes in thyrocytes exposed to the antithyroid preparations betazin and diiodotyrosine]. / Ul'trastrukturnye izmeneniia tirotsitov pri vozdeistvii antitireoidnykh preparatov--betazina i diiodtirozina.

Ultrastructure changes in the thyroid gland cells of rats were studied when feeding of bethazine and diiodthyrozine to rats at doses 0.01, 0.1 and 1.0 mg/kg of body's weight for 12 months. The ultrastructure changes in thyrocytes typical both for hyper- and for hypofunction of the gland were revealed.

A new method of preparing hapten-carrier immunogens by coupling with Saccharomyces cerevisiae by periodate oxidation.

A new method of preparing hapten-carrier immunogens is described. The carrier used was Saccharomyces cerevisiae yeast. Coupling was carried out with bovine serum albumin (BSA). BSA was conjugated with mannose residues of Saccharomyces cerevisiae cell walls, following periodate oxidation to produce aldehyde groups reactive with side chain amino groups of BSA. The coupling was stabilized and non-reactant aldehydes were blocked with sodium borohydride reduction. A hapten, 3,5,3',5'-tetraiodo-L-tyrosyl-L-tyrosine, was also coupled with the yeast. Anti-hapten antibodies were obtained in rabbit with this conjugate.

Gas-liquid chromatographic determination of mono- and diiodotyrosines in serum.

A sensitivie, reliable gas-chromatographic assay for monoiodotyrosine and diiodotyrosine in human serum is reported. The oxazolidinone-heptafluorobutyric anhydride derivatives allow the quantitation of both compounds in the linear range of 0.2 to 7.6 mg/L of serum. Analytical recovery averaged 88%, and mean accuracy and within-run precision were 98 and 2%, respectively. Concentrations of monoiodotyrosine in serum as low as 20 microgram/L and of diiodotyrosine as low as 100 microgram/L can be detected. Normal serum contains no detectable concentration of either compound, but the method is applicable as a diagnostic tool in the early prediction of thyroid disease. Both compounds were detected in the serum of a hypothyroid subject whose normal thyroid hormone concentrations were being maintained by therapy with desiccated thyroid extract.

Studies on the action mechanism of the antihemostatic effect of lodopeptides.

A synthetic iodopeptide having a glutamic acid-diiodotyrosine molar ratio of 1:1 has been shown to be an effective anticoagulant both in vivo and in vitro. Contrasted with heparin the following general conclusions may be made regarding its action. The iodopeptide does not act through the inactivation of thrombin in plasma. Iodopeptide does interact with fibrinogen to form a complex which, in vitro, is not soluble in buffered saline at physiological pH. At pH 8, iodopeptide interacts with fibrinogen to form a soluble complex in the presence of 0.9% NaCl that is not coaguable either by thrombin or Crotalus venom enzymes. All the available evidence indicates that the fibrinogen to fibrin conversion is not inhibited under these conditions, but that fibrin, once formed, is not able to polymerize due to interference by iodopeptide. Similar results were obtained with heparin in vitro with thrombin-fibrinogen mixtures in the absence of NaCl. Studies with Russell's viper venom in native PRP strongly suggest that the iodopeptide also interferes with processes in the early coagulation pathway associated with prothrombin activation.