A mitokondriális ATP-szenzitív káliumcsatorna aktiválásával létrehozott neuroprotekció mechanizmusa – egy új neuroprotektív stratégia vizsgálata = The mechanism of neuroprotection afforded by activation of mitochondrial ATP-sensitive potassium channels in the newborn – a novel neuroprotective experimental approach.

Az újszülöttkori agyi hipoxiát/iszkémiát követő idegrendszeri károsodások kialakulásában direkt neuronális mechanizmusok, valamint az ún. neurovaszkuláris egység diszfunkciója is fontos szerepet játszanak. Vizsgálatainkban a mitokondriumok belső membránjában található ATP-szenzitív káliumioncsatornák (mitoKATP) direkt farmakológiai aktivátorai által közvetített ún. farmakológiai prekondicionálást vizsgáltuk, ill. azt, hogy más farmakológiai támadáspontú vegyületek hasonló prekondicionáló hatása kapcsolatba hozható-e a mitoKATP vel. Ezeknek a vizsgálatoknak legfontosabb eredménye az, hogy míg a szelektív mitoKATP nyitók nem okoznak feltétlenül mitokondriális eredetű reaktív oxigénmetabolit (ROS) termelést, más hatékony farmakonok gyakran nem specifikus mitokondriális támadáspontokon, a mitokondriális ROS termeltetésén keresztül hozzák létre a prekondicionált fenotipust. In vivo vizsgálatainkban a neurovaszkuláris egység diszfunkcióját hipoxia/iszkémia érzékeny cerebrovaszkuláris érreakciók segítségével határoztuk meg. Kísérleti eredményeink egyrészt új információkkal gazdagították az érfunkciók károsodásának patomechanizmusát, másrészt sikerült új támadáspontokat azonosítani, melyek klinikai transzlációs kutatások alapját képezhetik, melyek az újszülöttkori hipoxiás/iszkémiás enkefalopátia kezelésében segíthetnek. | Following neonatal cerebral hipoxic/ischemic stress direct neuronal injury and the dysfunction of the so-called neurovascular unit both contribute to the developing encephalopathy. The pharmacological preconditioning induced by the activators of the mitochondrial ATP-sensitive potassium channels (mitoKATP) was investigated and whether other drugs with different primary actions would also trigger preconditioning through the involvement of mitoKATP. The most important message emanating from these studies was that though selective mitoKATP openers do not elevate mitochondrial reactive oxygen species (ROS) production, other effectively preconditioning drugs often create the preconditioned phenotype through non-specific actions on mitochondria mediated by ROS. lin the inner In our in vivo studies, neurovascular dysfunction was assessed with hypoxia/ischemia sensitive cerebrovascular responses. Our results provided new insights into the mechanism of altered cerebrovascular reactivity after hypoxic/ischemic stress, and they also identified new targets which after further translational studies may yield new therapies to treat hypoxic/ischemic encephalopathy in the newborn

Peri-infarktus depolarizáció (PID) akut fokális agyi ischemiában = Peri-infarct depolarization (PID) in acute focal cerebral ischemia

Az itt elvégzett kutatás célja az volt, hogy megértsük a stroke során kialakuló peri-infarktus depolarizációk (PID) természetét, és azok szerepét az agyi infarktus kiterjedésének növekedésében. Az előirányzott kísérletek újonnan kifejlesztett képalkotó eljárásokra támaszkodtak, melyeket a stroke különböző patkány modelljeiben alkalmaztunk. A kutatás során három fő célkitűzés teljesült: kifejlesztettünk egy többkomponensű képalkotó eljárást az agyi membránpotenciál-változások és a velük járó hemodinamikai jelenségek direkt megfigyelésére. A laboratóriumunkban kidolgozott módszert egy kísérletes, globális agyi ischemia modellben alkalmaztuk; eredményeink arra engedtek következtetni, hogy az így regisztrált PID-k az agyszövetre káros hatást fejtettek ki, és súlyosbították a stroke kimenetelét. Végül módszerünk segítségével a PID-k tulajdonságait egy kísérletes, fokális agyi ischemia modellben is jellemeztük, amelyben a korai fázisra jellemző PID-k valószínűleg nem növelték az ischemiás károsodás mértékét. Megfigyeléseink árnyalják az eddig érvényben levő hipotézist, mely szerint a PID-k minden esetben károsítják az ischemiás szövetet: azok a PID-k, amelyekkel nem jár repolarizáció és inverz neurovaszkuláris csatolás jellemzi, károsak a sérült agyszövetre, míg azok a PID-k amelyek a mebránpotenciál gyors helyreállásával és tranziens hiperémiával járnak, nem mélyítik at ischemiás károsodást. | Our overall aim was to improve our understanding of the genesis and propagation of stroke-related peri-infarct depolarization (PID), and of their contribution to infarct expansion and maturation. The proposed research relied on novel imaging techniques applied to relevant rat models. The research has obtained 3 goals: First, a multi-modal, live imaging strategy was established to monitor membrane potential variations and associated hemodynamic changes in the brain cortex directly. Second, the technology designed and developed in our lab was applied in a global ischemia model, in which PID proved to be deleterious to the tissue and are proposed to contribute to infarct evolution. Third, our method was used to detect PID in a focal ischemia model, in which early PID appeared to be harmless to the brain, and are suggested not to worsen ischemia outcome. Our observations modify the view held so far, that PID are invariably damaging to the brain tissue. Instead, PID that are not followed by the recovery of membrane potential and involve inverse neurovascular coupling (i.e. decreased CBF) are suggested to be destructive, while PID with repolarization and associated transient functional hyperemia appear not to be harmful to the nervous tissue

The short-term supplementation of monacolin K improves the lipid and metabolic patterns of hypertensive and hypercholesterolemic subjects at low cardiovascular risk

A nutraceutical compound containing 10 mg of MK appeared to be safe, well tolerated and effective at improving lipid and glucose patterns

Dental care protocol based on visual supports for children with autism spectrum disorders

Background : Subjects with Autism Spectrum Disorders (ASDs) have often difficulties to accept dental treatments. The aim of this study is to propose a dental care protocol based on visual supports to facilitate children with ASDs to undergo to oral examination and treatments. Material and Methods : 83 children (age range 6-12 years) with a signed consent form were enrolled; intellectual level, verbal fluency and cooperation grade were evaluated. Children were introduced into a four stages path in or der to undergo: an oral examination (stage 1), a professional oral hygiene session (stage 2), sealants (stage 3), and, if necessary, a restorative treatment (stage 4). Each stage came after a visual training, performed by a psychologist (stage 1) and by parents at home (stages 2, 3 and 4). Association between acceptance rates at each stage and gender, intellectual level, verbal fluency and cooperation grade was tested with chi-square test if appropriate. Results: Seventy-seven (92.8%) subjects overcame both stage 1 and 2. Six (7.2%) refused stage 3 and among the 44 subjects who need restorative treatments, only three refused it. The acceptance rate at each stage was statistically significant associated to the verbal fluency ( p =0.02; p =0.04; p =0.01, respectively for stage 1, 3 and 4). In stage 2 all subjects accepted to move to the next stage. The verbal/intellectual/cooperation dummy variable was statistically associated to the acceptance rate ( p <0.01). Conclusions: The use of visual supports has shown to be able to facilitate children with ASDs to undergo dental treatments even in non-verbal children with a low intellectual level, underlining that behavioural approach should be used as the first strategy to treat patients with ASDs in dental setting

Cerebral Microcirculatory Responses of Insulin-Resistant Rats are Preserved to Physiological and Pharmacological Stimuli

AbstractWe study a programming language with a built-in ground type for real numbers. In order for the language to be sufficiently expressive but still sequential, we consider a construction proposed by Boehm and Cartwright. The non-deterministic nature of the construction suggests the use of powerdomains in order to obtain a denotational semantics for the language. We show that the construction cannot be modelled by the Plotkin or Smyth powerdomains, but that the Hoare powerdomain gives a computationally adequate semantics. As is well known, Hoare semantics can be used in order to establish partial correctness only. Since computations on the reals are infinite, one cannot decompose total correctness into the conjunction of partial correctness and termination as is traditionally done. We instead introduce a suitable operational notion of strong convergence and show that total correctness can be proved by establishing partial correctness (using denotational methods) and strong convergence (using operational methods). We illustrate the technique with a representative example

Nkx2-5+Islet1+ Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Participate in Restoring Stromal Network Integrity

SummarySecondary lymphoid organ stromal cells comprise different subsets whose origins remain unknown. Herein, we exploit a genetic lineage-tracing approach to show that splenic fibroblastic reticular cells (FRCs), follicular dendritic cells (FDCs), marginal reticular cells (MRCs), and mural cells, but not endothelial cells, originate from embryonic mesenchymal progenitors of the Nkx2-5+Islet1+ lineage. This lineage include embryonic mesenchymal cells with lymphoid tissue organizer (LTo) activity capable also of supporting ectopic lymphoid-like structures and a subset of resident spleen stromal cells that proliferate and regenerate the splenic stromal microenvironment following resolution of a viral infection. These findings identify progenitor cells that generate stromal diversity in spleen development and repair and suggest the existence of multipotent stromal progenitors in the adult spleen with regenerative capacity

Helpers influence on territory use and maintenance in Alpine marmot groups

In social mammals, territory size and shape vary according to the number and strength of neighbour individuals competing for resources. Two main theories have been proposed to explain this variability: the Group Augmentation (GA) and the realized Resource Holding Potential (rRHP) hypotheses. The first states that the outcome of the interactions among groups depends on the total number of individuals in the group while the second states that only the number of animals directly involved in intergroup competition determines this outcome. We collected data on space use of individually tagged Alpine marmots ( Marmota marmota), a cooperative breeding species that overlaps part of its territory with neighbouring groups. In accordance with the rRHP hypothesis, we found that groups having higher proportion of helpers, rather than higher total number of individuals, had lower percentage of the territory overlapping with neighbouring groups and a larger area available for individual exclusive use

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy