In vitro skin models in the optimization of skin formulations.

BACKGROUND: Transdermal drug delivery is assumed to have a growing importance in drug development recently, thus it is crucial to optimize the penetration properties of drug into through the skin. Most of the current developments rely on the use of appropriate ex vivo animal or artificial models. However, the limited availability of human skin and the increasing restrictions in connection with animal testing encouraged the searchfor suitable artificial skin models. METHOD: For the review, we have searched the databases of scientific and medical research to collect the available publications about the in vitro skin models. Furthermore, we overviewed the methods of the DataBase service on ALternative Methods to animal experimentation (DB-ALM) database and the guidelines of Organisation for Economic Co-operation and Development (OECD). RESULTS: In vitro skin models have advantages like reproducibility, relatively low cost, easy storage, uncomplicated handling, and they offer a possibility for rapid screening and faster optimization of skin formulations. Furthermore, their composition can be easily modified which allows studying the relationship between certain pathological conditions and barrier function. However, the limitations of these models are needed to be taken into account. CONCLUSION: This review attempts to provide an overview of the most frequently used models, focusing on their limitations and advantages. Accessibility, easiness of the application, cost and the respective limitations have to be considered in order to choose the most appropriate in vitro model for the particular objective.

A possible association of HLA-DR beta 1*04 subtypes and rheumatoid arthritis of peptide binding region amino acids.

HLA-DR beta 1*04 subtypes associated with rheumatoid arthritis (RA) were studied by polymerase chain reaction with sequence specific primers and the 86th amino acid of the DR beta 1 chain was analysed in RA patients vs healthy controls. The frequency of HLA-DR beta 1*0401 and 0404/0407 alleles was significantly increased in RA patients vs the controls, HLA-DR beta 1*0401 and 0404 being the dominant variants in RA. In most RA patients hydrophilic glycine proved to be the 86th amino acid of the peptide binding region thus it could have an effect on the development of RA.

Molecular genetic analysis of HLA-DRB, -DQA, and -DQB polymorphisms in Hungarians and distribution of the DRB1*03 allele in adults and newborns.

We describe here the genetic variability of HLA-DRB1, -DQA, and -DQB in 140 healthy individuals from Hungary, including 95 randomly selected adults and 45 newborns. Allele and haplotype frequencies as well as linkage disequilibria were calculated. It was found that HLA-DRB1*11, -DQA1*0501, and -DQB1*0301 predominate in Hungarians. This information may be helpful in the future for HLA and disease association studies. Simultaneously, we observed that the frequency of the DRB1*03 allele differs between adults and newborns. Since it is well known that bearers of HLA-DR3 (and/or B8) antigens may display significant changes in immune parameters, the lower frequency in adults indicates that children with the DR3 antigen are predisposed to immune diseases in adulthood.