ABSTRACT
Background: Exposure to genotoxic stress such as radiation is an important public health issue affecting a large population. The necessity of analyzing cytogenetic effects of such exposure is related to the need to estimate the associated risk. Cytogenetic biological dosimetry is based on the relationship between the absorbed dose and the frequency of scored chromosomal aberrations. The influence of confounding factors on radiation response is a topical issue. The role of ethnicity is unclear. Here, we compared the dose-response curves obtained after irradiation of circulating lymphocytes from healthy donors of African and European ancestry. Materials and Methods: Blood samples from six Africans living in Africa, five Africans living in Europe, and five Caucasians living in Europe were exposed to various doses (0-4 Gy) of X-rays at a dose-rate of 0.1 Gy/min using an X-RAD320 irradiator. A validated cohort composed of 14 healthy Africans living in three African countries was included and blood samples were irradiated using the same protocols. Blood lymphocytes were cultured for 48 h and chromosomal aberrations scored during the first mitosis by telomere and centromere staining. The distribution of dicentric chromosomes was determined and the Kruskal-Wallis test was used to compare the dose-response curves of the two populations. Results: No spontaneous dicentric chromosomes were detected in African donors, thus establishing a very low background of unstable chromosomal aberrations relative to the European population. There was a significant difference in the dose response curves between native African and European donors. At 4 Gy, African donors showed a significantly lower frequency of dicentric chromosomes (p = 8.65 10-17), centric rings (p = 4.0310-14), and resulting double-strand-breaks (DSB) (p = 1.32 10-18) than European donors. In addition, a significant difference was found between African donors living in Europe and Africans living in Africa. Conclusion: This is the first study to demonstrate the important role of ethnic and environmental factors that may epigenetically influence the response to irradiation. It will be necessary to establish country-of-origen-specific dose response curves to practice precise and adequate biological dosimetry. This work opens new perspective for the comparison of treatments based on genotoxic agents, such as irradiation.
ABSTRACT
PURPOSE: Diabetes Type I is a chronic disease requiring insulin repeated injections by parenteral during a lifetime. This method of administration as well as traumatic can be a problem for adherence of patients to treatment. In order to overcome these difficulties, we considered the development of therapeutic transdermal drug delivery (TTDD) of insulin. MATERIAL AND METHOD: As active ingredient we used anhydrous human insulin Actarapid HM from Novo Nordisk laboratory, the excipients are ethyl cellulose, Eudragit RS 100 and butylphtalate. We developed two matrix Ethylcellulose/Eudragit in reports 1 and 2, in which are incorporated different proportions of insulin. RESULTS: The study of the release of insulin in phosphate buffer at pH 7.4, showed a continuous release profiles strongly depending on Ethylcellulose/Eudragit report and the initial charge of insulin. CONCLUSION: This study shows that the matrix Ethylcellulose/Eudragit lends itself to the development of a controlled release of insulin. This allows us to continue this work by combining this matrix with other elements for achieving an insulin TTDD.
