Blood Sampling from the Tail Vein, in Comparison with Two Other Techniques, Causes Less Stress to Mice

It is important to use the optimal method for repeated blood sampling to ensure minimal stress to mice,  and also to provide better pharmacokinetic and pharmacodynamic data. The aim of the present study was  to compare the impact of blood sampling methods on corticosterone and adrenocorticotropic hormone  (ACTH) levels in mice. Hsdwin:NMRI mice were divided into four sampling groups: control group (I), vena facialis (II), tail vein  (III) and saphenous vein (IV). The first blood samples, obtained from vena facialis, tail or saphenous vein  of conscious mice, were taken at time point 0. The second blood sample was taken by decapitation from  groups II-IV with isoflurane anaesthesia at time point 20 min. The control group animals were anesthetized  and decapitated at 20 min time point. Corticosterone levels in plasma were analyzed at time point 0 and 20  min, and ACTH at time point 20 min. Saphenous bled mice, in comparison with vena facialis and tail vein sampled mice, indicated statistically  significant greater (P < 0.05) level of corticosterone at sampling point (0 min). Rising levels of corticosterone  in all groups differed statistically (P < 0.05) from the control group level, indicating that all tested bleeding  methods were stressful to the experimental animals. However, the tail vein bleeding method stressed  statistically significantly (P < 0.05) less in comparison with vena facialis and saphenous vein bleeding.  At time point 20 min, only saphenous vein bled mice showed statistically significant greater (P < 0.05)  blood levels of ACTH compared to tail vein bled mice. Conditions in sampling and rising levels of corticosterone and/or ACTH level did not show direct correlation.  In conclusion the results suggest that the tail bleeding method accomplished least stress to mice and next  less vena facialis bleeding. Blood collection technique from the saphenous vein was the most stressful to  the experimental animals.

Visualizing multi-dimensional pareto-optimal fronts with a 3D virtual reality system

In multiobjective optimization, there are several targets that are in conflict, and thus they all cannot reach their optimum simultaneously. Hence, the solutions of the problem form a set of compromised trade-off solutions (a Pareto-optimal front or Pareto-optimal solutions) from which the best solution for the particular problem can be chosen. However, finding that best compromise solution is not an easy task for the human mind. Pareto-optimal fronts are often visualized for this purpose because in this way a comparison between solutions according to their location on the Pareto-optimal front becomes somewhat easier. Visualizing a Pareto-optimal front is straightforward when there are only two targets (or objective functions), but visualizing a front for more than two objective functions becomes a difficult task. In this paper, we introduce a new and innovative method of using three-dimensional virtual reality (VR) facilities to present multi-dimensional Pareto-optimal fronts. Rotation, zooming and other navigation possibilities of VR facilities make easy to compare different trade-off solutions, and fewer solutions need to be explored in order to understand the interrelationships among conflicting objective functions. In addition, it can be used to highlight and characterize interesting features of specific Pareto-optimal solutions, such as whether a particular solution is close to a constraint boundary or whether a solution lies on a relatively steep trade-off region. Based on these additional visual aids for analyzing trade-off solutions, a preferred compromise solution may be easier to choose than by other means

Antitumor effect of oncolytic virus and paclitaxel encapsulated in extracellular vesicles for lung cancer treatment

Standard of care for cancer is commonly a combination of surgery with radiotherapy or chemoradiotherapy. However, in some advanced cancer patients this approach might still remaininefficient and may cause many side effects, including severe complications and even death. Oncolytic viruses exhibit different anti-cancer mechanisms compared with conventional therapies, allowing the possibility for improved effect in cancer therapy. Chemotherapeutics combined with oncolytic viruses exhibit stronger cytotoxic responses and oncolysis. Here, we have investigated the systemic delivery of the oncolytic adenovirus and paclitaxel encapsulated in extracellular vesicles (EV) formulation that, in vitro, significantly increased the transduction ratio and the infectious titer when compared with the virus and paclitaxel alone. We demonstrated that the obtained EV formulation reduced the in vivo tumor growth in animal xenograft model of human lung cancer. Indeed, we found that combined treatment of oncolytic adenovirus and paclitaxel encapsulated in EV has enhanced anticancer effects both in vitro and in vivo in lung cancer models. Transcriptomic comparison carried out on the explanted xenografts from the different treatment groups revealed that only 5.3% of the differentially expressed genes were overlapping indicating that a de novo genetic program is triggered by the presence of the encapsulated paclitaxel: this novel genetic program might be responsible of the observed enhanced antitumor effect. Our work provides a promising approach combining anticancer drugs and viral therapies by intravenous EV delivery as a strategy for the lung cancer treatment.Peer reviewe

Effect of Hydrogen Peroxide on Immersion Challenge of Rainbow Trout Fry with Flavobacterium psychrophilum

An experimental model for immersion challenge of rainbow trout fry (Oncorhynchus mykiss) with Flavobacterium psychrophilum, the causative agent of rainbow trout fry syndrome and bacterial cold water disease was established in the present study. Although injection-based infection models are reliable and produce high levels of mortality attempts to establish a reproducible immersion model have been less successful. Various concentrations of hydrogen peroxide (H₂O₂) were evaluated before being used as a pre-treatment stressor prior to immersion exposure to F. psychrophilum. H₂O₂ accelerated the onset of mortality and increased mortality approximately two-fold; from 9.1% to 19.2% and from 14.7% to 30.3% in two separate experiments. Clinical signs observed in the infected fish corresponded to symptoms characteristically seen during natural outbreaks. These findings indicate that pre-treatment with H₂O₂ can increase the level of mortality in rainbow trout fry after exposure to F. psychrophilum