The Banning of Sportsmen and Women Who Fail Drug Tests Is Unjustifiable.

The banning of sportsmen and women who fail drug tests is unjustifiable.

J R Coll Physicians Edinb. 2013 Mar; 43(1): 39-43
Shuster S, Devine JW

The use of performance enhancing drugs among elite athletes has been in the headlines recently, particularly with Lance Armstrong’s fall from grace and his admission about widespread doping. Many argue that the use of drugs confers an unfair advantage and is ultimately dangerous to the health of the athletes. Others, like Professor Shuster, argue that the use of drugs is no different from other techniques employed by athletes to boost their performance: swimmers shaving their body hair; skiers wearing sleek body armour; archers and shooters having laser eye surgery to improve their accuracy. Professor Shuster puts forward the provocative argument that since ‘there is no acceptable proof (that) drugs improve competitive performance and their use is no different from accepted sports practice, banning them is wrong and immoral.’ JW Devine argues the other side, that the use of performance enhancing drugs poses a ‘significant risk to the health of athletes’ and perhaps more importantly, ‘threatens to undermine the very purpose of sport’ by disrupting the ‘balance of excellences’. HubMed – drug

Biomimetic construction of large engineered bone using hemoperfusion and cyto-capture in traumatic bone defect.

Biores Open Access. 2012 Oct; 1(5): 247-51
Liu F, Yu S, Wang Z, Sun X

Due to lack of blood vessel systems, only a few tissues, such as skin, cartilage, and cornea, have been successfully constructed in vivo. Anticoagulative scaffolds have been used in drug-eluting stent systems both in animal studies and clinical therapies, as in the medicinal leech therapy used to salvage venous-congested microvascular free flaps improved perfusion inspired us to tackle this hurdle in bone tissue engineering. We hypothesize that a combination of bone marrow as the blood supply and a heparin/chitosan-coated acellular bone matrix that acts like hirudin, together with a vacuum-assisted closure therapy system, would provide blood perfusion to the scaffold. Using these methods, a biomimetically engineered bone construct would facilitate clinical translation in bone tissue engineering and offer new therapeutic strategies for reconstructing large bone defects if the hypothesis proves to be practical. HubMed – drug

Comparative Study of Transcriptome Profiles of Mechanical- and Skin-Transformed Schistosoma mansoni Schistosomula.

PLoS Negl Trop Dis. 2013 Mar; 7(3): e2091
Protasio AV, Dunne DW, Berriman M

Schistosome infection begins with the penetration of cercariae through healthy unbroken host skin. This process leads to the transformation of the free-living larvae into obligate parasites called schistosomula. This irreversible transformation, which occurs in as little as two hours, involves casting the cercaria tail and complete remodelling of the surface membrane. At this stage, parasites are vulnerable to host immune attack and oxidative stress. Consequently, the mechanisms by which the parasite recognises and swiftly adapts to the human host are still the subject of many studies, especially in the context of development of intervention strategies against schistosomiasis infection. Because obtaining enough material from in vivo infections is not always feasible for such studies, the transformation process is often mimicked in the laboratory by application of shear pressure to a cercarial sample resulting in mechanically transformed (MT) schistosomula. These parasites share remarkable morphological and biochemical similarity to the naturally transformed counterparts and have been considered a good proxy for parasites undergoing natural infection. Relying on this equivalency, MT schistosomula have been used almost exclusively in high-throughput studies of gene expression, identification of drug targets and identification of effective drugs against schistosomes. However, the transcriptional equivalency between skin-transformed (ST) and MT schistosomula has never been proven. In our approach to compare these two types of schistosomula preparations and to explore differences in gene expression triggered by the presence of a skin barrier, we performed RNA-seq transcriptome profiling of ST and MT schistosomula at 24 hours post transformation. We report that these two very distinct schistosomula preparations differ only in the expression of 38 genes (out of ?11,000), providing convincing evidence to resolve the skin vs. mechanical long-lasting controversy. HubMed – drug

Comparison of Human Hepatoma HepaRG Cells with Human and Rat Hepatocytes in Uptake Transport Assays in Order to Predict a Risk of Drug Induced Hepatotoxicity.

PLoS One. 2013; 8(3): e59432
Szabo M, Veres Z, Baranyai Z, Jakab F, Jemnitz K

Human hepatocytes are the gold standard for toxicological studies but they have several drawbacks, like scarce availability, high inter-individual variability, a short lifetime, which limits their applicability. The aim of our investigations was to determine, whether HepaRG cells could replace human hepatocytes in uptake experiments for toxicity studies. HepaRG is a hepatoma cell line with most hepatic functions, including a considerable expression of uptake transporters in contrast to other hepatic immortalized cell lines. We compared the effect of cholestatic drugs (bosentan, cyclosporinA, troglitazone,) and bromosulfophthalein on the uptake of taurocholate and estrone-3-sulfate in human and rat hepatocytes and HepaRG cells. The substrate uptake was significantly slower in HepaRG cells than in human hepatocytes, still, in the presence of drugs we observed a concentration dependent decrease in uptake. In all cell types, the culture time had a significant impact not only on the uptake process but on the inhibitory effect of drugs too. The most significant drug effect was measured at 4 h after seeding. Our report is among the first concerning interactions of the uptake transporters in the HepaRG, at the functional level. Results of the present study clearly show that concerning the inhibition of taurocholate uptake by cholestatic drugs, HepaRG cells are closer to human hepatocytes than rat hepatocytes. In conclusion, we demonstrated that HepaRG cells may provide a suitable tool for hepatic uptake studies. HubMed – drug