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M Cîrstea

Publications and source records attributed to M Cîrstea.

53 records · Page 3Linked to original sources

The discrepancy between the inhibitory activity induced on passive hemagglutination by the free and conjugated hapten. The significance of the phenomenon for the explanation of the drug allergy.

The capacity of the free and conjugated haptens to inhibit passive hemagglutination has been comparatively studied in five immunological systems, using hapten specific antisera prepared in rabbits and conjugates of the respective haptens with rabbit serum proteins. The results demonstrate that the affinity of the free hapten for the specific antibodies is 100 to 10,000 times lower than the affinity of the conjugated hapten. This finding constitutes an explanation for the occurrence of the allergic drug reactions under the circumstances where the concentrations of the free hapten are much higher than the concentrations of the hapten bound in in vivo formed conjugates. Using the passive hemagglutination inhibition test, the affinity of the various forms of a given hapten for the specific antibodies can be comparatively evaluated.

Animals↗

The diagnostic value of intradermal tests with penicilloyl-dextran and aspiryl-polylysine.

Intradermal tests (i.d.t.) with penicillin (P) and penicilloyl-dextran (P-Dex) were performed in 32 penicillin allergic patients and in 37 controls with allergy to other drugs. The incidence of the positive i.d.t. was much higher in the group of penicillin allergy of immediate type (17 of 18 patients) than in the group of penicillin allergy of half-late or late type (4 of 14 cases). I.d.t. with P and P-Dex were concordant in 75% of cases. Among 28 patients with penicillin allergy tested with both reagents, i.d.t. positive only to P-Dex were found in two cases. The utilisation of i.d.t. with P-Dex or penicilloyl-polylysine (PPL) in penicillin allergy furnishes, therefore, only very modest additional information besides that furnished by i.d.t. performed with plain penicillin. I.d.t. with aspiryl-polylysine (APL) were performed in 23 patients with aspirin allergy/intolerance and in 60 controls with allergy to other drugs. 70% of the individuals with aspirin allergy and 27% of the patients with allergy to other drugs showed positive i.d.t. to APL. Although the specificity of i.d.t. with APL in aspirin allergy seems lower than that of i.d.t. with P-Dex and PPL in penicillin allergy, a positive cutaneous test with APL may constitute an important argument for the allergic nature of an aspirin adverse reaction evoking an allergic mechanism.

Aspirin↗

On the relation between the formation of antihapten and anti-carrier protein antibodies in the immune response induced by conjugates of various haptens with homologous serum proteins.

Rabbits inoculated with conjugates of homologous serum with ortho-aminophenol (OAP), para-aminophenol (PAP), 3-hydroxy-sulfanilamide (3-HS), DOPA and alpha-methyldopa (alpha MD), 5-aminosalicylic acid (5-ASA) and 3-hydroxy-para-aminobenzoic acid (3-HPABA) give rise to both hapten specific and anti-carrier protein antibodies. By contrast, the conjugates of homologous serum with penicilloyl (P) hapten induced only antihapten antibodies. The conclusion is, therefore, drawn that the formation of anti-carrier antibodies upon inoculation with conjugates of various haptens appears to be dependent on the nature of hapten in the conjugate. The discrepancy between the behaviour of P conjugates, on the one hand, and the DOPA and alpha MD conjugates, on the other hand, is in agreement with the observation from the clinical immunology, which has signaled a high incidence of antibodies with autoantibody character in patients taking DOPA and alpha MD, but rarely, if ever, such antibodies have been found in patients treated with penicillin.

Animals↗

Studies on the sensitizing activity of alpha-chymotrypsin in man.

The sensitizing effect of alpha-chymotrypsin was followed up in a group of 116 women to whom parenteral treatment with this drug was associated to antibiotic therapy for various chronic inflammatory gynecopathies. The mean antibody titre to alpha-chymotrypsin, assayed by a passive hemagglutination technique, and the mean intensity of the intradermal tests with this drug were found significantly higher in 15 patients previously treated with alpha-chymotrypsin by comparison with 16 non-treated controls. A significant direct correlation was found between the titre of anti-alpha-chymotrypsin antibodies and the intensity of the intradermal tests. In 12 patients who had not previously been treated with alpha-chymotrypsin the antibody titre and the intensity of the intradermal tests rose significantly after a series of 10 injections with this drug. Eight of 116 patients (approximately 7%) treated with alpha-chymotrypsin developed overt symptoms of sensitization to the drug. The symptoms announcing the sensitization, the relation with the amount of the drug administered and the diagnostic value of intradermal tests are analysed. No relation was found between the presence of atopy and the sensitization to other drugs, on the one hand, and the sensitization to alpha-chymotrypsin, on the other hand.

Adult↗

Variations of catecholamines in mixed shock. Therapeutic implications. Experimental and clinical investigations.

The variations of catecholamines, cortisol and aldosterone in mixed shock (traumatic, hemorrhagic and septic) were studied experimentally and clinically. In the stage of collapse adrenaline decreased by 81.4% and noradrenaline by 62.6% as compared with the preoperative values. These decreases were found to be directly proportional to the decrease of arterial blood pressure, pulse amplitude and diuresis as well as to the slowing down or even stop of microcirculation. The value of plasma cortisol increased in the stage of collapse by 98.3% and that of aldosterone by 66.27% as compared with the preoperative values. Treatment with a pharmacodynamic sympatheticolytic-vasopressor-adrenocortical mixture is recommanded when the blood pressure remains below 50--60 mm Hg for 1--2 hrs and when the treatment for the correction of hypovolemia with fluids and sympatheticolytics has failed. Clinically, this treatment gave good results in 34 of the 58 cases studied (58.6%).

Aldosterone↗

Experimental studies on drug sensitization. II. Production of antiacetylsalicylyl antibodies and their detection by passive hemagglutination.

Antiacetylsalicylyl antibodies were produced in rabbits and guinea-pigs by innoculation of acetylsalicylic acid incorporated in Freund adjuvant. These antibodies were readily detected by a passive hemagglutination test using rabbit erythrocytes incubated with acetylsalicylic acid at alkaline pH. Acetylsalicylyl conjugates with human gammaglobulin, bovine gammaglobulin and rabbit gammaglobulin were also prepared by incubating the proteins with acetylsalicylic acid at alkaline pH. In parallel experiments, salicylic acid did not induce formation of specific antibodies capable of reacting with acetylsalicylic or salicylic acid-treated erythrocytes.

Animals↗

Spontaneous formation of immunogenic conjugates by 5-aminosalicylic acid--a biotransformation product of salicylazosulfapyridine.

5-Aminosalicylic acid (5-ASA) reacts readily with proteins at alkaline pH and forms conjugates capable to induce hapten specific antibodies in rabbits. Extensive immunological cross reactions have been found between 5-ASA and para-aminophenol (PAP) immunological systems, but no cross reactions were found between 5-ASA and orto-aminophenol (OAP) immunological systems. Moderate cross reactions were found, occasionally between 5-ASA, 3-hydroxy-sulfanilamide (3-HS) and alpha-methyldopa (alpha MD) immunological systems. Antibodies directed against normal rabbit serum (NRS) proteins, which served as carrier in the 5-ASA conjugates used for immunization, were found in the sera of three out of the six rabbits inoculated with such conjugates. Antibodies directed against heterologous proteins were found in all of these sera, including one serum which lacked hapten specific antibodies and the three sera lacking antibodies directed against NRS proteins. The significance of these findings for the interpretation of the immuno-allergic reactions induced by sulfasalazine is discussed.

Aminosalicylic Acids↗

Penicilloyl-dextran conjugates as reagents for skin testing in penicillin allergy.

A procedure for implanting amino groups in the dextran molecule is described. The aminated polymer prepared from a dextran sample with a molecular weight of 20,000 was found to contain approximately 16 amino groups per molecule. Similarly to polylysine, the aminated dextran may be penicilloylated by incubation with penicillin at high pH. The penicilloyl-dextran (P-Dex) conjugate prepared in this way was found to contain approximately 8 penicilloyl (PO) groups per molecule. P-Dex was found practically nonimmunogenic in rabbits and showed itself antigenically active in precipitin, passive hemagglutination and passive cutaneous anaphylaxis (PCA) tests performed with a PO specific antiserum. A good correlation was found between the skin tests performed parallelly with P-Dex and penicilloyl-polylysine (PPL) in four subjects with penicillin allergy.

Animals↗

Spontaneous formation of conjugates of alpha-methyl-DOPA and DOPA with serum proteins and experimental production of specific antibodies against these haptens.

Alpha-methyldopa (alpha MD) and levodopa (DOPA) react readily with serum proteins at alkaline pH and form stable conjugates with them. Hapten specific antibodies in high titers are produced in rabbits by inoculation of the conjugates formed by alpha MD and DOPA with normal rabbit serum (alpha MD-NRS and DOPA-NRS), incorporated in incomplete Fruend adjuvant. No hapten specific antibodies were raised in rabbits inoculated with alpha MD as such, incorporated in adjuvant, with alpha MD mixed with autologous serum 24 hrs before inoculation, or with alpha MD conjugates with autologous serum administered without adjuvant. Hapten specific antibodies were, however, found in one of six rabbits inoculated with alpha MD conjugates with homologous serum proteins given without adjuvant. Extensive crossreactivity was found between alpha MD and DOPA immunological systems. High titers of antibodies directed against normal rabbit serum proteins as well as against human gamma globulin were also found in the sera of the rabbits immunized with alpha MD-NRS and DOPA-NRS conjugates incorporated in Freund adjuvant. A close correlation was found between the titers of hapten specific antibodies and of anti-protein antibodies.

Animals↗

Spontaneous formation of immunogenic conjugates by 3-hydroxy-para-aminobenzoic acid--a biotransformation product of procaine and para-aminobenzoic acid.

3-Hydroxy-para-aminobenzoic acid (3-HPABA), a biotransformation product of procaine and para-aminobenzoic acid, is capable of binding covalently to proteins by simple incubation at alkaline pH. When administered incorporated in Freund adjuvant to rabbits, 3-HPABA conjugates with normal rabbit serum proteins (3-HPABA-NRS) give rise to both hapten specific antibodies and anti-NRS antibodies. Cross immunological reactions were found between 3-HPABA and ortho-aminophenol (OAP) and 3-hydroxy-sulfanilamide (3-HS) immunological systems, but not between 3-HPABA and para-aminophenol (PAP) and 5-aminosalicyclic acid (5-ASA) immunological systems. The significance of these findings for the explanation of procaine allergy and the possible use of 3-HPABA conjugates for skin testing in procaine hypersensitivity is discussed.

4-Aminobenzoic Acid↗

Spontaneous formation of immunogenic conjugates by ortho- and para-aminophenol.

Ortho-aminophenol (OAP) and para-aminophenol (PAP) react readily with proteins at alkaline pH giving rise to conjugates capable to induce hapten specific antibodies in rabbits. PAP and OAP immunological systems do not cross react with each other, but both anti-PAP and anti-OAP serum give intense cross passive hemagglutination reactions with hydroquinone and pyrocatechin conjugates prepared by the same procedure. PAP immunological system does not cross react with various systems of the "para" group in which the conjugates were prepared by diazotization. PAP proved unable to induce formation of specific antibodies when inoculated in Freund adjuvant into rabbits and both PAP and OAP were unable to sensitize erythrocytes by incubation at alkaline pH. The findings are discussed in the light of data from literature showing that some drugs with amino aromatic structure are transformed in the body into compounds with PAP or OAP structure which might be able to form immunogenic conjugates with autologous proteins in vivo.

Aminophenols↗