Gene expression changes induced by ochratoxin A in renal and hepatic tissues of male F344 rat after oral repeated administration

Ochratoxin A (OTA), a naturally occurring mycotoxin, is nephrotoxic in all animal species tested and is considered a potent renal carcinogen, particularly in male rats. Its mechanism of toxicity is still unknown, although oxidative stress appears to be a plausible mechanism. Therefore, the objective of this study was to identify the biological pathways that are modulated in vivo by OTA in male F344 rats in order to gain further insight into its mechanism of renal toxicity. Rats were gavaged daily with OTA (500 microg/kg bw) and gene expression profiles in target and non-target organs were analyzed after 7 and 21 days administration. As was expected, a time-dependent increase of OTA concentrations was found in plasma, kidney and liver, with the concentrations found in both tissues being quite similar. However, histopathological examinations only revealed changes in kidney; signs of nephrotoxicity involving single cell necrosis and karyomegalic nuclei were observed in the treated rats. The number of differentially expressed genes in kidney was much higher than in liver (541 versus 11 at both time points). Several similarities were observed with other in vivo gene expression data. However, great differences were found with previous in vitro gene expression data, with the exception of DNA damage response which was not observed at mRNA level in any of our study conditions. Down-regulation was the predominant effect. Oxidative stress response pathway and genes involved in metabolism and transport were inhibited at both time points. RGN (regucalcin) - a gene implicated in calcium homeostasis - was strongly inhibited at both time points and genes implicated in cell survival and proliferation were up-regulated at day 21. Moreover, translation factors and annexin genes were up-regulated at both time points. Apart from oxidative stress, alterations of the calcium homeostasis and cytoskeleton structure may be present at the first events of OTA toxicity.     

Self‐Assembling Amphiphilic Hyperbranched Polyglycerol–Polystyrene Copolymers for Encapsulation

Phospholipids, dendrimers, and polymers are each able to assemble to form vesicles, but each has limitations such as leakiness and multistep syntheses. A new class of versatile amphiphilic block copolymers is reported containing hyperbranched polyglycerol (HPG) and polystyrene (PS) units. These compounds self‐assemble into polymersomes (HPGsomes). Under solvent exchange methods, amphiphilic polystyrene‐HPG diblock (PS‐b‐HPG) structures are self‐assembled and characterized by transmission electron microscopy. The assemblies are robust up to 95 °C in polar, protic solvents, and encapsulate dyes with minimal release. Polymersomes are typically assembled from linear amphiphilic polymers; however, it is shown that combining linear and hyperbranched polymers is a feasible strategy to encapsulation.

     

Validity of a three-dimensional public-domain system for contemporary endodontic research

The purpose of this study was to evaluate the limits and benefits of a visualization system based on public-domain software for contemporary three-dimensional (3-D) endodontic research purposes. Three-dimensional bio-models of six human teeth and of one bone-implant specimen were generated using cross-sectional imaging. To evaluate the overall performance in processing large data sets and in reproducing accurate 3-D morphology, slices with a thickness varying from 100 microm to 10 microm were cut. Auto-outlining and segmenting techniques were tested. The 3-D bio-models represented in accurate detail the different morphological aspects of the specimen. Voxel volumes of 0.116 x 10(-5) mm3 could be realized and were only restricted by the computer hardware limitations. The system is not limited to dental hard tissues. Hypomineralized material and soft tissues as well as bone- and allogeneic-implant material could be visualized. The method presented is valid and meets current requirements applying to endodontic research. The broad-based use of high-quality, public-domain software and the resulting exchange of experience help to manage resources and may contribute to enhancing the in-process quality of research.     

Osteoblast precursors at different anatomic sites

Skeletal morphology depends on the local regulation of bone formation, both in a quantitative and qualitative sense. The formative cells, osteoblasts, adjust their synthetic activity in response to signals that influence cell differentiation and matrix production. Here, we review data concerning the morphological patterning during bone ontogenesis and its direct cause: osteoblasts at specific anatomic sites. An overview of the possible origins of osteogenic cells is presented, considering bone growth and homeostasis, and discussing the repair process. A testable model is proposed, in which functional differences between osteoblast populations are explained by homeobox-gene regulation. Newly developed markers for osteoblast recruitment and differentiation provide an experimental system to test the impact of homeobox-gene expression on osteoblast differentiation and bone matrix production.