Chronic treatment with rofecoxib but not ischemic preconditioning of the myocardium ameliorates early intestinal damage following cardiac ischemia/reperfusion injury in rats

There is some recent evidence that cardiac ischemia/reperfusion (I/R) injury induces intestinal damage within days, which contributes to adverse cardiovascular outcomes after myocardial infarction. However, it is not clear whether remote gut injury has any detectable early signs, and whether different interventions aiming to reduce cardiac damage are also effective at protecting the intestine. Previously, we found that chronic treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2), limited myocardial infarct size to a comparable extent as cardiac ischemic preconditioning (IPC) in rats subjected to 30-min coronary artery occlusion and 120-min reperfusion. In the present study, we aimed to analyse the early intestinal alterations caused by cardiac I/R injury, with or without the above-mentioned infart size-limiting interventions. We found that cardiac I/R injury induced histological changes in the small intestine within 2 h, which were accompanied by elevated tissue level of COX-2 and showed positive correlation with the activity of matrix metalloproteinase-2 (MMP-2), but not of MMP-9 in the plasma. All these changes were prevented by rofecoxib treatment. By contrast, cardiac IPC failed to reduce intestinal injury and plasma MMP-2 activity, although it prevented the transient reduction in jejunal blood flow in response to cardiac I/R. Our results demonstrate for the first time that rapid development of intestinal damage follows cardiac I/R, and that two similarly effective infarct size-limiting interventions, rofecoxib treatment and cardiac IPC, have different impacts on cardiac I/R-induced gut injury. Furthermore, intestinal damage correlates with plasma MMP-2 activity, which may be a biomarker for its early diagnosis

Biochemical and pharmacological characterization of three opioid-nociceptin hybrid peptide ligands reveals substantially differing modes of their actions

In an attempt to design opioid-nociceptin hybrid peptides, three novel bivalent ligands, H-YGGFGGGRYYRIK-NH2, H-YGGFRYYRIK-NH2 and Ac-RYYRIKGGGYGGFL-OH were synthesized and studied by biochemical, pharmacological, biophysical and molecular modelling tools. These chimeric molecules consist of YGGF sequence, a crucial motif in the N-terminus of natural opioid peptides, and Ac-RYYRIK-NH2, which was isolated from a combinatorial peptide library as an antagonist or partial agonist that inhibits the biological activity of the endogenously occurring heptadecapeptide nociceptin. Solution structures for the peptides were studied by analysing their circular dichroism spectra. Receptor binding affinities were measured by equilibrium competition experiments using four highly selective radioligands. G-protein activating properties of the multitarget peptides were estimated in [35S]GTPγS binding tests. The three compounds were also measured in electrically stimulated mouse vas deferens (MVD) bioassay. H-YGGFGGGRYYRIK-NH2 (BA55), carrying N-terminal opioid and C-terminal nociceptin-like sequences interconnected with GGG tripeptide spacer displayed a tendency of having either unordered or β-sheet structures, was moderately potent in MVD and possessed a NOP/KOP receptor preference. A similar peptide without spacer H-YGGFRYYRIK-NH2 (BA62) exhibited the weakest effect in MVD, more α-helical periodicity was present in its structure and it exhibited the most efficacious agonist actions in the G-protein stimulation assays. The third hybrid peptide Ac-RYYRIKGGGYGGFL-OH (BA61) unexpectedly displayed opioid receptor affinities, because the opioid message motif is hidden within the C-terminus. The designed chimeric peptide ligands presented in this study accommodate well into a group of multitarget opioid compounds that include opioid-non-opioid peptide dimer analogues, dual non-peptide dimers and mixed peptide- non-peptide bifunctional ligands

Adalékok a megújuló energiaforrásokra alapozott projektek fenntarthatósági értékeléséhez

A globális ökológiai problémák a fenntarthatóság felé való átmenetet sürgetik, ennek eredményessége érdekében azonban a környezet- és fejlesztéspolitikai tervezésben a megújuló energiaforrások értékelését a lehető legalaposabban, komplex módon kell elvégezni. Tanulmányunk célja a megújuló energiaforrásokra alapozott technológiák összehasonlítása az alapján, hogy mennyire járulnak hozzá a környezeti állapot megóvásának, a gazdaság és a társadalom fejlődésének együttes igényéhez – tehát a fenntartható fejlődéshez. Munkánk során felmértük a hazai szakértők véleményét a megújuló energetikai technológiák fenntarthatósági jellemzőinek fontosságáról. A megkérdezettek a területigényt és a társadalmi vonatkozásokat tartották a leglényegesebbnek. Ezt követően 23 magyar projekt elemzése alapján arra a következtetésre jutottunk, hogy előnyben részesítendők a helyi jövedelmet fokozottan termelő beruházások, valamint hogy kiemelten támogatandó projektek a nagyobb szélerőműparkok, a geotermikus távfűtés, illetve a kisléptékű biomassza-tüzelés. ------------------------------------------------- Transition toward sustainability is being driven by the global ecological problems. For planning the efficiency of this transition in environmental and development policies the assessment of renewable energy sources in an elaborate and complex way is required. The aim of the study is to consider the contribution of renewable energy based technologies to environmental protection and socio-economic development – and thus to sustainable development. The opinion of Hungarian experts regarding the attributes of renewable energy based technologies was examined. The primacy of land demand as well as social aspects was stated. An analysis of numerous Hungarian renewable energy based projects was then undertaken. We concluded that the profitability on the local market was the priority of the investors. Also the advantages of large-scale wind utilisation, the geothermal district heating and the small-scale biomass burning were shown

ASPECTS OF THE SUSTAINABLE UTILIZATION OF RENEWABLE ENERGY SOURCES

The aim of this paper is to analyze the main approaches to sustainability and to present an alternative interpretation for the issues involved in the utilization of RES. The utilization technologies can be described by the average values of several technological parameters. Some significant parameters were chosen which are the most relevant for the issue of sustainability. The group of attributes was composed of these parameters in the analysis, which was conducted by the choice experiment (CE) methodology. The examination of each attributes’ influence on the individual’s preferences and choices was made possible by this method and the preferences of the relevant experts were determined. The weight of the attributes was defined by experts according to the importance of each attribute regarding RES-based technologies. The importance of sustainability attributes implies the significance of sustainability in the case of RES technologies, which thus highlights the characteristics of the more prosperous technological parameters regarding sustainable development

Targeted Imaging and Therapeutic Technologies in Neuroregeneration

Extremity injuries are less likely to be fatal than head, chest, and abdominal wounds; however, they can be severely disabling. Peripheral nerve injury (PNI) can result from trauma (lacerations, penetrating injury, stretching, ischemia or crushing trauma and fractures, and gunshot wounds), repetitive compression (tunnel syndromes), or iatrogenic causes (orthopedic, plastic, neurosurgical or other surgical procedures such as oncologic resection). Nerve regeneration is an essential process needed for the recovery of function. However, our understanding of this process is still rather limited, and access to successful personalized regeneration supportive treatment is lacking. This chapter focuses on surveying new technological advances such as targeted nanoimaging and immunomodulation in support of neuroregeneration following peripheral injuries. Specifically, we highlight new nanotechnology advances in targeted cell tracking and imaging, as well as targeted drug delivery and cellular therapeutics. Though most of this work is preclinical, we hope that these advances drive the development of novel, safe and effective clinical solutions