The Appearance of Endothelium in Small Arteries After Treatment with 5-Fluorouracil. An Electron Microscopic Study of Late Effects in Rabbits

Cardiotoxicity is an unexplained toxic manifestation of 5-fluorouracil (5-FU). Its possible mechanism could be a direct cytotoxic effect on the vascular endothelium. We have tested this hypothesis in an experimental study in rabbits, using scanning and transmission electron microscopic evaluation of endothelium in small arteries (the central artery of the ear). The perfusion fixation method at physiological pressure and temperature was used. Both local and systemic effects of 5-FU on endothelium were studied 1, 3, 7, 14 and 30 days after in vivo treatment with 5-FU. Fifteen rabbits were used and five additional animals served as controls. The following parameters were evaluated: vessel wall and endothelial cell contraction, cell oedema, cytolysis, occurrence of denuded areas, platelet adhesion/aggregation and fibrin formation. For the description of each parameter, a scale of negative points (0.0-3.0) was used. We found severe cell damage with accompanying thrombus formation. The findings support the hypothesis that the thrombogenic effect of 5-FU, secondary to its direct cytotoxic effect on endothelium, is the pathophysiological mechanism behind 5-FU cardiotoxicity

Barley grain at Uppåkra, Sweden: evidence for selection in the Iron Age

A metric analysis on hulled barley grain from the Iron Age regional centre of Uppåkra and surrounding sites in southern Sweden has identified a variation in the size of the grain found on these archaeological sites. Large, high-quality grain was found more frequently at Uppåkra when compared to sites in the surrounding area, where smaller grain was more frequent. The observed large grain found at Uppåkra was, however, restricted to only a few house contexts, including hall-buildings, while other contexts on the site, such as areas dedicated to craft production, had barley assemblages containing smaller grain, similar to the size range found on the surrounding sites. The intra-site variation between different contexts at Uppåkra points to a degree of sorting for larger grain and that this variation between grain assemblages was the result of selection after the crop processing was completed. The distribution of grain size at Uppåkra shows a pattern that indicates that the high-quality barley grain was indented for specific individuals or households. The different contexts at Uppåkra have together produced a record spanning the first millennium ad, representing almost the whole existence of the site. The evidence for selection of larger grain can be seen in the hall-buildings throughout most of the first millennium ad, although less prominently during the Late Roman Iron Age (ad 200–400), while during the Migration Period (ad 400–550) several houses on the main site Uppåkra had assemblages of large grain size. The distribution of grain size at the regional centre Uppåkra shows a pattern that indicates that the handling of large high-quality barley grain was part of a spatial organization, and such organization is similar to other functions observed on the site. The long-term record of grain size patterns across time shows that a structure for handling grain was already in place during the early phase of the settlement and that it remained for centuries. This study indicates that the affluence otherwise seen at the regional centre Uppåkra from an abundance of high-status objects, could also include agricultural wealth, with extensive access to high-quality grain