Heterotopic Cervical Heart Transplantation in Mice

The heterotopic cervical heart transplantation in mice is a valuable tool in transplant and cardiovascular research. The cuff technique greatly simplifies this model by avoiding challenging suture anastomoses of small vessels thereby reducing warm ischemia time. In comparison to abdominal graft implantation the cervical model is less invasive and the implanted graft is easily accessible for further follow-up examinations. Anastomoses are performed by pulling the ascending aorta of the graft over the cuff with the recipient’s common carotid artery and by pulling the main pulmonary artery over the cuff with the external jugular vein. Selection of appropriate cuff size and complete mobilization of the vessels are important for successful revascularization. Ischemia-reperfusion (I/R) injury can be minimized by perfusing the graft with a cardioplegic solution and by hypothermia. In this article, we provide technical details for a simplified and improved cuff technique, which should allow surgeons with basic microsurgical skills to perform the procedure with a high success rate.     

Novel quinolizidine salicylamide influenza fusion inhibitors.

A novel series of quinolizidine salicylamides was synthesized as specific inhibitors of the H1 subtype of influenza A viruses. These inhibitors inhibit the pH-induced fusion process, thereby blocking viral entry into host cells. Compound 16 was the most active inhibitor in this series with an EC50 of 0.25 microg/mL in plaque reduction assay. The synthesis and the SAR of these compounds are discussed.     

Estimating the distribution of heterogeneous treatment effects from treatment responses and from a predictive biomarker in a parallel-group RCT: A structural model approach

When the objective is to administer the best of two treatments to an individual, it is necessary to know his or her individual treatment effects (ITEs) and the correlation between the potential responses (PRs) and under treatments 1 and 0. Data that are generated in a parallel-group design RCT does not allow the ITE to be determined because only two samples from the marginal distributions of these PRs are observed and not the corresponding joint distribution. This is due to the “fundamental problem of causal inference.” Here, we present a counterfactual approach for estimating the joint distribution of two normally distributed responses to two treatments. This joint distribution of the PRs and can be estimated by assuming a bivariate normal distribution for the PRs and by using a normally distributed baseline biomarker functionally related to the sum . Such a functional relationship is plausible since a biomarker and the sum encode for the same information in an RCT, namely the variation between subjects. The estimation of the joint trivariate distribution is subjected to some constraints. These constraints can be framed in the context of linear regressions with regard to the proportions of variances in the responses explained and with regard to the residual variation. This presents new insights on the presence of treatment–biomarker interactions. We applied our approach to example data on exercise and heart rate and extended the approach to survival data.     

Local Enclosures of Globalization. The Power of Locality

In the discussion of globalization and localization, the mainperspectives are either to unveil how global issues are localized, or toanalyze local modifications resulting form global integration. Incontrast, a perspective from the local to the global is proposed to beable to point at local contents of globalization. Such a perspectiverequires an analysis of how locality is constructed locally. In much ofthe current discussion local stands for places, indigenous people,villages, cities, quarters within cities, factories, regions, nations orplaces. Following older research on ethnicity and recent studies ofmigrant cultures, locality is described as a social construction, whichconnects space, local knowledge and social organization. Locality isconnected to support among those belonging to the locality, interestsand the control of resources. Thus competition and potential conflict islinked to locality. Therefore, speaking of locality implies speaking ofpower-differentials. Whether a locality can assume a dominant positionvis-à-vis other localities and define its discourses as dominantor even as universal depends on its organizational and integrativecapacity for the mobilization and application of resources. Thoughcontrol of resources required by others, the respective local knowledgebecomes a necessity for gaining access to these resources. Consequently,global discourses can and often do have a local background. Accordingly,globalization in quite often global dominance from particular localcontext.     

Noradrenaline as a putative neurotransmitter mediating hypotension—induced FOs—like immunoreactivity in the supraoptic nucleus of the rat

Hemorrhage or hypotension induces extensive Fos-like immunoreactivity in the magnocellular neurosecretory cells in the supraoptic nucleus of the hypothalamus in rat,especially in the vasopressin neurons.The present study was to explore the neurotransmitter mediating this effect,Microinfusion of the alpha-adrenergic blocker into the supraoptic nucleus reduced the hypotension-induced FOs.whereas beta-antagonist did not affect it significantly.Alaha1-and alpha2-antagonist,prazosin and yohimbine,both reduced the Fos-Positive cell counts.However,the effective dosage of yohimbine was much larger,Alpha1-agonist,methoxamine,induced abundant Fos-like immunoreactivity in the vasopressin cells in this nucleus,while beta-and alpha2-agonist did not elicit such effect.Administration of the noradrenergic re-uptake inhibitor desipramine,to this nucleus to locally accumulate the spontaneously released noradrenaline from the nerve terminals also induced Fos expression,mostly in the vasopressin cells.