scholarly journals STUDIES ON THE MECHANISM OF THE FORMATION OF THE PENICILLIN ANTIGEN

1960 ◽  
Vol 112 (6) ◽  
pp. 1131-1156 ◽  
Author(s):  
Bernard B. Levine
Keyword(s):  
Contact Dermatitis ◽  
Guinea Pig ◽  
Degradation Products ◽  
Contact Allergy ◽  
Test System ◽  
Penicillin G ◽  
Allergic Contact ◽  
The Relationship

Seven highly purified degradation products of penicillin G (PG) were examined with regard to their ability to cross-react allergically with PG. Guinea pig allergic contact dermatitis was employed as the test system. Three of these degradation products, D-benzylpenicillenic acid (BPE), D-penicillamine, and D-α-benzylpenicilloic acid were found to cross-react with PG and also to be capable of inducing delayed contact allergy in the guinea pig. BPE and PG cross-reacted with particularly intense reactions, and other immunologic experiments indicated that PG and BPE introduce identical allergic determinant groups into epidermal proteins. These experimental results were correlated with the results of previous studies concerning the degradation pathways of PG under physiological conditions in vitro, and the chemical reactivities of these degradation products. Based on these immunologic and chemical data, a schema is proposed which suggests the chemical pathways by which PG may react with epidermal proteins in vivo to form the penicillin antigen. The identity of the specific antigenic determinant groups of the penicillin antigen is suggested. The relationship between PG allergy of the contact dermatitis type in the guinea pig and PG allergy of the immediate type in man is discussed.

Imidazolidinyl urea activates mast cells via MRGPRX2 to induce non-histaminergic allergy

2021 ◽  
Author(s):  
Jiapan Gao ◽  
Delu Che ◽  
Xueshan Du ◽  
Yi Zheng ◽  
Huiling Jing ◽  
...  
Keyword(s):  
Contact Dermatitis ◽  
Mast Cells ◽  
Pharmaceutical Products ◽  
Drug Induced ◽  
Inflammatory Infiltration ◽  
Local Inflammatory Response ◽  
Allergic Contact ◽  
G Protein Coupled

Abstract Imidazolidinyl urea (IU) is used as an antimicrobial preservative in cosmetic and pharmaceutical products. IU induces allergic contact dermatitis, however, the mechanism has not yet been elucidated. Mas-related G protein-coupled receptor-X2 (MRGPRX2) triggers drug-induced pseudo-allergic reactions. The aims of this study were to determine whether IU activated mast cells through MRGPRX2 to further trigger contact dermatitis. Wild-type (WT) and KitW-sh/HNihrJaeBsmJNju (MUT) mice were treated with IU to observe its effects on local inflammation and mast cells degranulation in vivo. Laboratory of allergic disease 2 cells were used to detect calcium mobilization and release of inflammatory mediators in vitro. WT mice showed a severe local inflammatory response and contact dermatitis, whereas only slight inflammatory infiltration was observed in MUT mice. Thus, MRGPRX2 mediated the IU-induced activation of mast cells. However, histamine, a typical allergen, was not involved in this process. Tryptase expressed by mast cells was the major non-histaminergic inflammatory mediator of contact dermatitis. IU induced anaphylactic reaction via MRGPRX2 and further triggering non-histaminergic contact dermatitis, which explained why antihistamines are clinically ineffective against some chronic dermatitis.

scholarly journals Even Apparently Insignificant Chemical Deviations among Bioequivalent Generic Antibiotics Can Lead to Therapeutic Nonequivalence: the Case of Meropenem

2013 ◽  
Vol 58 (2) ◽  
pp. 1005-1018 ◽  
Author(s):  
M. Agudelo ◽  
C. A. Rodriguez ◽  
C. A. Pelaez ◽  
O. Vesga
Keyword(s):  
Guinea Pig ◽  
Susceptibility Testing ◽  
Degradation Products ◽  
Active Pharmaceutical Ingredient ◽  
Infection Model ◽  
Content Type ◽  
Infection Models ◽  
Generic Products

ABSTRACTSeveral studies with animal models have demonstrated that bioequivalence of generic products of antibiotics like vancomycin, as currently defined, do not guarantee therapeutic equivalence. However, the amounts and characteristics of impurities and degradation products in these formulations do not violate the requirements of the U.S. Pharmacopeia (USP). Here, we provide experimental data with three generic products of meropenem that help in understanding how these apparently insignificant chemical differences affect thein vivoefficacy. Meropenem generics were compared with the innovatorin vitroby microbiological assay, susceptibility testing, and liquid chromatography/mass spectrometry (LC/MS) analysis andin vivowith the neutropenic guinea pig soleus infection model (Pseudomonas aeruginosa) and the neutropenic mouse thigh (P. aeruginosa), brain (P. aeruginosa), and lung (Klebisella pneumoniae) infection models, adding the dihydropeptidase I (DHP-I) inhibitor cilastatin in different proportions to the carbapenem. We found that the concentration and potency of the active pharmaceutical ingredient,in vitrosusceptibility testing, and mouse pharmacokinetics were identical for all products; however, two generics differed significantly from the innovator in the guinea pig and mouse models, while the third generic was therapeutically equivalent under all conditions. Trisodium adducts in a bioequivalent generic made it more susceptible to DHP-I hydrolysis and less stable at room temperature, explaining its therapeutic nonequivalence. We conclude that the therapeutic nonequivalence of generic products of meropenem is due to greater susceptibility to DHP-I hydrolysis. These failing generics are compliant with USP requirements and would remain undetectable under current regulations.

Airborne allergic contact dermatitis caused by Machaerium scleroxylon : Confirmation by in vivo and in vitro tests

2019 ◽  
Vol 81 (4) ◽  
pp. 296-298 ◽  
Author(s):  
Katharina Hansel ◽  
Nicola Murgia ◽  
Anna Russano ◽  
Francesco Crescenzi ◽  
Marta Tramontana ◽  
...  
Keyword(s):  
Contact Dermatitis ◽  
Allergic Contact Dermatitis ◽  
In Vitro Tests ◽  
Allergic Contact

In Vitro and In Vivo Testing Techniques for Allergic Contact Dermatitis

Dermatitis ◽  
1998 ◽  
Vol 9 (2) ◽  
pp. 111-118
Author(s):  
G. Frank Gerberick ◽  
Elizabeth E. Sikorski
Keyword(s):  
Contact Dermatitis ◽  
Allergic Contact Dermatitis ◽  
In Vivo Testing ◽  
Testing Techniques ◽  
Allergic Contact

Xanthone suppresses allergic contact dermatitis in vitro and in vivo

2020 ◽  
Vol 78 ◽  
pp. 106061 ◽  
Author(s):  
Aye Aye ◽  
Young-Jae Song ◽  
Yong-Deok Jeon ◽  
Jong-Sik Jin
Keyword(s):  
Contact Dermatitis ◽  
Allergic Contact Dermatitis ◽  
Allergic Contact

scholarly journals Patch Testing for Contact Allergy and Allergic Contact Dermatitis

2008 ◽  
Vol 1 (1) ◽  
pp. 42-51 ◽  
Author(s):  
Radoslaw Spiewak
Keyword(s):  
Contact Dermatitis ◽  
Allergic Contact Dermatitis ◽  
Patch Test ◽  
Contact Allergy ◽  
Diagnostic Methods ◽  
Test Results ◽  
Costs Of Treatment ◽  
Allergic Contact

Contact allergy (CA) is alteration of immune response with readiness to develop an inflammatory reaction against a specific substance of low molecular weight (hapten). The prevalence of CA is estimated at 26-40% among adults, and 21-36% children. A proportion of people with CA will remain asymptomatic, among the rest, the most frequent clinical manifestation is allergic contact dermatitis (ACD) with lifetime prevalence estimated at 10%. Less frequent manifestations include allergic contact stomatitis, conjunctivitis, vaginitis, systemic reactions, implant intolerance, and rarely urticaria, asthma, and allergic rhinitis. Patch test (epicutaneous test) is the gold standard in the diagnosis of CA and ACD: Performing the test significantly increases probability of accurate diagnosis, reduces costs of treatment, and leads to improved patients’ quality of life. Patch test results may be influenced by patient’s medication and health status, and interpretation requires due knowledge and experience. Other diagnostic methods are more laborious and not validated; no in vitro tests are available for routine application at present.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

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