ABSTRACT
Cardiovascular and reproductive health of women have been going hand in hand since the dawn of time, however, their links have been poorly studied and once the basis of their connections started to be established in late 20th century, it depended on local regional abilities and the level of progressive thinking to afford comprehensive women’s care beyond the “bikini medicine”. Further research identified different associations rendering more conditions sex-specific and launching therefore a slow, yet initial turn around in clinical trials’ concept as the majority of global cardiovascular guidelines rely on the results of research conducted on a very modest percentage of women and even less on the women of color. Currently, the concept of women’s heart centers varies depending on the local demographics’ guided needs, available logistics driven by budgeting and societal support of a broad-minded thinking environment, free of bias for everyone: from young adults questioning their gender identity, via women of reproductive age both struggling to conceive or keep working part time when healthy and line of work permits it during pregnancy, up to aging and the elderly. Using “Investigate-Educate-Advocate-Legislate” as the four pillars of advancing cardiovascular care of women, we aimed to sum-marize standing of women’s health in Serbia, present ongoing projects and propose actionable solutions for the future. © 2021, Serbia Medical Society. All rights reserved.
ABSTRACT
Dermal absorption of chemicals is a key factor in non-dietary human risk assessment with agrochemicals. A ring trial exploring the dermal absorption potential of 14C-Caffeine was investigated in six laboratories under GLP conditions using the OECD TG 428-compliant in vitro assay with flow-through cells and dermatomed human skin. Potential sources of variation were reduced by a common protocol, test item and skin source. Particularly, skin samples from the same donors were distributed over two repeats and between labs in a non-random, stratified design. The data show very similar recovery in the various investigated compartments of the assay between laboratories, repeats and donors, which demonstrates that the assay can be robustly and reliably performed. A low intra-lab variability was demonstrated in all 6 laboratories participating. Further, a low inter-lab variability was notable in five out of six laboratories resulting in mean caffeine absorption estimates of 3.93 ± 2.96 % of the applied dose (4 mg/mL) and a mean overall compound recovery of 99.03 ± 2.11 %. In the remaining laboratory presumably due to a Covid-19 driven shipment delay of the skin samples, the skin quality may have been affected since the receptor fluid recovery was substantially higher and to a certain degree did correlate with skin integrity parameters. Overall, the ring trial's results demonstrate that the OECD TG 428-compliant in vitro assay can be robustly and reliably performed in different laboratories. Skin absorption results for caffeine did not present any statistically significant variability, with minor differences in the results across the laboratories (5/6) and indicates the robustness of the methodology and the positive impact of strictly controlling the variables in the study. Understanding the variability in the in vitro dermal absorption assay with human skin will continue contributing to the design and conduct of appropriate regulatory studies, and adding further considerations to the existing OECD dermal guidance notes. This will result in greater confidence in the data utilised from these assays in risk assessments by companies and regulators alike.