Dexmedetomidine preconditioning ameliorates kidney ischemia-reperfusion injury

e00045Kidney ischemia-reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor (α2-AR) agonist, protects against kidney I/R injury. Sprague–Dawley rats were divided into four groups: (1) Sham-operated group; (2) I/R group (40 min ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 μg/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 μg/kg). The effects of Dex postconditiong (Dex 1 or 10 μg/kg i.v. after reperfusion) as well as the effects of peripheral α2-AR agonism with fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney protein kinase B, toll like receptor 4, light chain 3B, p38 mitogen-activated protein kinase (p38 MAPK), sirtuin 1, adenosine monophosphate kinase (AMPK), and endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury-induced renal dysfunction, acute tubular necrosis and inflammatory response. Neither pre- nor postconditioning with fadolmidine protected kidneys. Dex decreased blood pressure more than fadolmidine, ameliorated I/R-induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular, integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid-derived 2)-like 2 pathways, whereas aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38-CD44-pathway and possibly also through ischemic preconditioning.Peer reviewe

Naisurheilijan oireyhtymä : liikaa urheilua ja liian vähän ruokaa

Naisurheilijan oireyhtymällä tarkoitetaan tilaa, jossa runsaasti urheileva nainen kärsii ainakin yhdestä seuraavista kolmesta oireesta: 1) niukka energiansaanti (häiriintyneen syömisen tai muun syyn takia), 2) kuukautiskierron häiriöt tai 3) pienentynyt luuntiheys. Oireyhtymä johtuu liian vähäisestä ravinnonsaannista suhteessa energiankulutukseen. Tutkimusten mukaan naisurheilijan oireyhtymä on yleinen ilmiö: yhdestä oireesta kärsii jopa 16-60% naisurheilijoista. Oireyhtymä ei rajoitu pelkkiin huippu-urheilijoihin, vaan sitä tavataan myös aktiivisesti liikkuvilla tytöillä ja naisilla. Suurimmassa vaarassa ovat laihduttavat tytöt ja naiset sekä urheilijat, joita painostetaan laihtumaan. Vakavimmat haitat ovat syömishäiriön puhkeaminen ja luuston heikentyminen, minkä takia kasvuikäisten oireiden tunnistaminen on tärkeää. Varhaiseen tunnistamiseen ei vielä ole vakiintunutta käytäntöä, minkä takia kliininen haastattelu ja tutkimus ovat tärkeässä asemassa. Niukka energiansaanti voi ilmetä viimeaikaisena laihtumisena, alipainona tai häiriintyneenä syömisenä. Kuukautiskierron häiriöt voidaan todeta naisurheilijan oireyhtymästä johtuviksi, kun muut syyt on poissuljettu. Luuntiheyttä voidaan tarvittaessa mitata kaksienergiaisella absorptiometrimenetelmällä. Ylidiagnostiikkaa on syytä välttää, kun oireyhtymä on lievä ja lyhytkestoinen. Hoidossa tärkeintä on riittävän ravinnonsaannin turvaaminen. Tavoitteena on saavuttaa urheilijan ”hyvinvointipaino”, jonka myötä kuukautiset käynnistyvät ja toimivat häiriöttä. Painonnousua ja kuukautisten palaamista seuraavat myöhemmin suotuisat luustovaikutukset. Kilpaurheilijan kohdalla hoitosuunnitelma mietitään yhdessä urheilijan, hoitavan tahon ja valmennustahon kanssa. Toipuminen on suurilta osin mahdollista, mutta siihen voi kulua vuosia. (192 sanaa

New forms of radio in Europe and in Finland

The aim of this Master's Thesis is to map out, what new and emerging technological advances are made in radio in Europe, what options are there, whether and how it is going to evolve and if this evolution may affect the listening experience and if it will, how. In addition to the technology itself, the technological process is an issue of both politics and economics. From the technological point of view, the study focuses in a limited set of the main new forms of radio in Europe: the digital radios, radio on the Internet and the hybrid radio formats. The predominant debate related to radio's technological process in Europe concerns the radio digitalisation project and whether digital radio format DAB (Digital audio broadcasting) will replace the analogue FM radio network. The theoretical framework of this study lies in the historical context of new mass media technologies and their diffusion to the society. The future of the radio as a broadcasting technology can be mirrored to its own history but also to several other broadcasting technologies and the socio-economical and political impacts of their introduction and diffusion to the mass media consumption. Also, recent studies and news articles concerning the current state of radio's technological process are an important part of creating a thorough image of how radio is evolving in each of the focus countries. The methodology of this study is a simplified version of the Delphi method commonly associated to the future studies: The study includes interviews with six experts from different European countries from specific different areas in order to cover all the necessary aspects radio's current state and possible futures. The focus countries represented in the study are the Czech Republic, Finland, France, Norway, Switzerland and the United Kingdom, all with very different paths when it comes to the evolution of the radio. The findings of the study suggest that out of the six focus countries, five are all on their path to radio digitalisation. Norway is the first one to complete the shutdown of its FM network by the end of 2017. The Norwegian process is observed with anticipation by the countries still in earlier stages of the digitalisation. Finland is the only country within the group that has no plans when it comes to digital radio. The future of the radio in Europe is believed to be digital but also hybrid as internet- related services and features are introduced in various forms to the radio audiences. The Internet offers an additional service platform but, according to the experts interviewed, is not going to replace the traditional forms of radio. Whether the analogue radio will be completely replaced by the digital radio is still uncertain. It will however not happen before the 2030s

Kohonneen verenpaineen ja ravinnon suolan vaikutukset suolistomikrobiston koostumukseen ja toimintaan

Suoliston mikrobistolla on osoitettu olevan vahva yhteys useisiin suolistosairauksiin samoin kuin moniin systeemisiin sairauksiin, kuten lihavuuteen, diabetekseen ja eräisiin neurologisiin sairauksiin. Näissä tautitiloissa suoliston mikrobiston koostumus ja toiminta on häiriintynyt (dysbioosi). Uusimpien tutkimustulosten perusteella suolistomikrobiston dysbioosilla saattaa lisäksi olla merkittävä vaikutus sydän- ja verisuonitautien synnyssä. Tämän tutkimuksen tavoitteena oli selvittää verenpainetaudin kokeellista tautimallia hyödyntäen, vaikuttaako kohonnut verenpaine ja ravinnon suola suolistomikrobiston koostumukseen ja toimintaan. Verenpainetaudin kokeellisena tautimallina käytettiin spontaanisti hypertensiivisiä rottia (SHR), joille verenpainetauti kohde-elinvaurioineen kehittyy geneettisistä syistä. Normaalipaineisena verrokkiryhmänä käytettiin Wistar-Kyoto rottia (WKY), joista on aikoinaan risteytyksen avulla kehitetty SHR-kanta. Koe-eläinkannat jaettiin saamaan joko normaalisuolaista tai runsassuolaista ravintoa. Verenpainetaudin kehittymistä seurattiin mittaamalla koe-eläinten verenpainetta häntämittarilla kahdeksan viikon seuranta-aikana. Suolistomikrobiston koostumus selvitettiin määrittämällä ulostenäytteistä eristetystä DNA:sta 16S sekvensoinnilla. Suolistomikrobiston toimintaa arvioitiin määrittämällä seeruminäytteistä yli 650:n aineenvaihduntatuotteen pitoisuudet UPLC-MS/MS-laitteella. Tutkimuksessa osoitettiin, että verenpainetautia sairastavien koe-eläinten suolistomikrobiston koostumus poikkesi merkittävästi normaalipaineisten koe-eläinten koostumuksesta. Lisäksi havaitsimme, että runsassuolainen ravinto muutti suolistomikrobiston koostumusta myös verenpainetaudista riippumatta. Seeruminäytteiden metabolomiikka-analyysit osoittivat, että useat suolistomikrobien muodostamat metaboliitit imeytyvät suolistosta, jolloin niitä voidaan havaita verenkierrosta biologisesti aktiivisina pitoisuuksina. Verenpainetautia sairastavien koe-eläinten seerumissa eräiden metaboliittien pitoisuudet olivat merkittävästi korkeammat normaalipaineisiin koe-eläimiin verrattuna. Havainto viittaa siihen, että metaboliittien muodostuminen on lisääntynyt suolistossa ja/tai metaboliittien läpäisevyys suoliston seinämästä on verenpainetaudissa lisääntynyt. Yksi mielenkiintoisimmista havaituista metaboliiteista oli fenyyliasetyyliglysiini, jonka veripitoisuutta sekä verenpainetauti että runsassuolainen ravinto nostivat merkittävästi. Fenyyliasetyyliglysiini on aikaisemmin yhdistetty sydänpotilaiden suurentuneeseen kuolleisuusriskiin sekä verisuonten lisääntyneeseen tukosriskiin. Kaiken kaikkiaan runsassuolainen ravinto aiheutti merkittävästi laajemmat muutokset seeruminäytteiden metabolomiikassa normaalipaineisille koe-eläimille verenpainetautia sairastaviin verrattuna. Havainto saattaa viitata siihen, että suolistomikrobien muodostamat metaboliitit osallistuvat suolaresistenssiyden muodostumiseen. Lisäksi tutkimuksessa arvioitiin suolistomikrobien ja verenpainetaudin syy-seuraussuhdetta suorittamalla ulosteensiirto mikrobivapaisiin hiiriin (”germ-free mice”). Ulosteensiirto verenpainetautia sairastavilta koe-eläimiltä kohotti verenpainetta merkittävästi enemmän kuin ulosteensiirto normaalipaineisilta koe-eläimiltä. Havainto viittaa siihen, että suolistomikrobit ja niiden muodostamat metaboliitit osallistuvat keskeisesti verenpainetaudin kehittymiseen. Tutkimuksen perusteella suolistomikrobit ja niiden muodostamat metaboliitit voisivat olla lupaavia lääkekehityksen kohdemolekyylejä kehitettäessä uusia hoitoja sydän- ja verisuonitautien ennaltaehkäisyyn ja hoitoon. (311 sanaa

The effect of 50% compared to 100% inspired oxygen fraction on brain oxygenation and post cardiac arrest mitochondrial function in experimental cardiac arrest

Background and aim: We hypothesised that the use of 50% compared to 100% oxygen maintains cerebral oxygenation and ameliorates the disturbance of cardiac mitochondrial respiration during cardiopulmonary resuscitation (CPR). Methods: Ventricular fibrillation (VF) was induced electrically in anaesthetised healthy adult pigs and left untreated for seven minutes followed by randomisation to manual ventilation with 50% or 100% oxygen and mechanical chest compressions (LUCAS (R)). Defibrillation was performed at thirteen minutes and repeated if necessary every two minutes with 1 mg intravenous adrenaline. Cerebral oxygenation was measured with near-infrared spectroscopy (rSO(2), INVOS (TM) 5100C Cerebral Oximeter) and with a probe (NEUROVENT-PTO, RAUMEDIC) in the frontal brain cortex (PbO2). Heart biopsies were obtained 20 min after the return of spontaneous circulation (ROSC) with an analysis of mitochondrial respiration (OROBOROS Instruments Corp., Innsbruck, Austria), and compared to four control animals without VF and CPR. Brain rSO(2) and PbO2 were log transformed and analysed with a mixed linear model and mitochondrial respiration with an analysis of variance. Results: Of the twenty pigs, one had a breach of protocol and was excluded, leaving nine pigs in the 50% group and ten in the 100% group. Return of spontaneous circulation (ROSC) was achieved in six pigs in the 50% group and eight in the 100% group. The rSO(2) (p = 0.007) was lower with FiO(2) 50%, but the PbO2 was not (p = 0.93). After ROSC there were significant interactions between time and FiO(2) regarding both rSO(2) (p = 0.001) and PbO2 (p = 0.004). Compared to the controls, mitochondrial respiration was decreased, with adenosine diphosphate (ADP) levels of 57 (17) pmol s(-1) mg(-1) compared to 92 (23) pmol s(-1) mg(-1) (p = 0.008), but there was no difference between different oxygen fractions (p = 0.79). Conclusions: The use of 50% oxygen during CPR results in lower cerebral oximetry values compared to 100% oxygen but there is no difference in brain tissue oxygen. Cardiac arrest disturbs cardiac mitochondrial respiration, but it is not alleviated with the use of 50% compared to 100% oxygen (Ethical and hospital approvals ESAVI/1077/04.10.07/2016 and HUS/215/2016, 7 30.3.2016, Funding Helsinki University and others). (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

HiPS-Endothelial Cells Acquire Cardiac Endothelial Phenotype in Co-culture With hiPS-Cardiomyocytes

Cell-cell interactions are crucial for organ development and function. In the heart, endothelial cells engage in bidirectional communication with cardiomyocytes regulating cardiac development and growth. We aimed to elucidate the organotypic development of cardiac endothelial cells and cardiomyocyte and endothelial cell crosstalk using human induced pluripotent stem cells (hiPSC). Single-cell RNA sequencing was performed with hiPSC-derived cardiomyocytes (hiPS-CMs) and endothelial cells (hiPS-ECs) in mono- and co-culture. The presence of hiPS-CMs led to increased expression of transcripts related to vascular development and maturation, cardiac development, as well as cardiac endothelial cell and endocardium-specific genes in hiPS-ECs. Interestingly, co-culture induced the expression of cardiomyocyte myofibrillar genes and MYL7 and MYL4 protein expression was detected in hiPS-ECs. Major regulators of BMP- and Notch-signaling pathways were induced in both cell types in co-culture. These results reflect the findings from animal studies and extend them to human endothelial cells, demonstrating the importance of EC-CM interactions during development.Peer reviewe

Structural and Functional Support by Left Atrial Appendage Transplant to the Left Ventricle after a Myocardial Infarction

The left atrial appendage (LAA) of the adult heart has been shown to contain cardiac and myeloid progenitor cells. The resident myeloid progenitor population expresses an array of pro-regenerative paracrine factors. Cardiac constructs have been shown to inhibit deleterious remodeling of the heart using physical support. Due to these aspects, LAA holds promise as a regenerative transplant. LAAs from adult mT/mG mice were transplanted to the recipient 129X1-SvJ mice simultaneously as myocardial infarction (MI) was performed. A decellularized LAA patch was implanted in the control group. Two weeks after MI, the LAA patch had integrated to the ventricular wall, and migrated cells were seen in the MI area. The cells had two main phenotypes: small F4/80+ cells and large troponin C+ cells. After follow-up at 8 weeks, the LAA patch remained viable, and the functional status of the heart improved. Cardiac echo demonstrated that, after 6 weeks, the mice in the LAA-patch-treated group showed an increasing and statistically significant improvement in cardiac performance when compared to the MI and MI + decellularized patch controls. Physical patch-support (LAA and decellularized LAA patch) had an equal effect on the inhibition of deleterious remodeling, but only the LAA patch inhibited the hypertrophic response. Our study demonstrates that the LAA transplantation has the potential for use as a treatment for myocardial infarction. This method can putatively combine cell therapy (regenerative effect) and physical support (inhibition of deleterious remodeling).Peer reviewe

Structural and Functional Support by Left Atrial Appendage Transplant to the Left Ventricle after a Myocardial Infarction

The left atrial appendage (LAA) of the adult heart has been shown to contain cardiac and myeloid progenitor cells. The resident myeloid progenitor population expresses an array of pro-regenerative paracrine factors. Cardiac constructs have been shown to inhibit deleterious remodeling of the heart using physical support. Due to these aspects, LAA holds promise as a regenerative transplant. LAAs from adult mT/mG mice were transplanted to the recipient 129X1-SvJ mice simultaneously as myocardial infarction (MI) was performed. A decellularized LAA patch was implanted in the control group. Two weeks after MI, the LAA patch had integrated to the ventricular wall, and migrated cells were seen in the MI area. The cells had two main phenotypes: small F4/80+ cells and large troponin C+ cells. After follow-up at 8 weeks, the LAA patch remained viable, and the functional status of the heart improved. Cardiac echo demonstrated that, after 6 weeks, the mice in the LAA-patch-treated group showed an increasing and statistically significant improvement in cardiac performance when compared to the MI and MI + decellularized patch controls. Physical patch-support (LAA and decellularized LAA patch) had an equal effect on the inhibition of deleterious remodeling, but only the LAA patch inhibited the hypertrophic response. Our study demonstrates that the LAA transplantation has the potential for use as a treatment for myocardial infarction. This method can putatively combine cell therapy (regenerative effect) and physical support (inhibition of deleterious remodeling).Peer reviewe