Myoblastilauttaterapia sydäninfarktin jälkeisen vajaatoiminnan hoidossa

Heart failure is a common, severe, and progressive condition associated with high mortality and morbidity. Because of population-aging in the coming decades, heart failure is estimated to reach epidemic proportions. Current medical and surgical treatments have reduced mortality, but the prognosis for patients has remained poor. Transplantation of skeletal myoblasts has raised hope of regenerating the failing heart and compensating for lost cardiac contractile tissue. In the present work, we studied epicardial transplantation of tissue-engineered myoblast sheets for treatment of heart failure. We employed a rat model of myocardial infarction-induced acute and chronic heart failure by left anterior descending coronary artery ligation. We then transplanted myoblast sheets genetically modified to resist cell death after transplantation by expressing antiapoptotic gene bcl2. In addition, we evaluated the regenerative capacity of myoblast sheets expressing the cardioprotective cytokine hepatocyte growth factor in a rat chronic heart failure model. Furthermore, we utilized in vitro cardiomyocyte and endothelial cell culture models as well as microarray gene expression analysis to elucidate molecular mechanisms mediating the therapeutic effects of myoblast sheet transplantation. Our results demonstrate that Bcl2-expression prolonged myoblast sheet survival in rat hearts after transplantation and induced secretion of cardioprotective, proangiogenic cytokines. After acute myocardial infarction, these sheets attenuated left ventricular dysfunction and myocardial damage, and they induced therapeutic angiogenesis. In the chronic heart failure model, inhibition of graft apoptosis by Bcl-2 improved cardiac function, supported survival of cardiomyocytes in the infarcted area, and induced angiogenesis in a vascular endothelial growth factor receptor 1- and 2-dependent mechanism. Hepatocyte growth factor-secreting myoblast sheets further enhanced the angiogenic efficacy of myoblast sheet therapy. Moreover, myoblast-secreted paracrine factors protected cardiomyocytes against oxidative stress in an epidermal growth factor receptor- and c-Met dependent manner. This protection was associated with induction of antioxidative genes and activation of the unfolded protein response. Our results provide evidence that inhibiting myoblast sheet apoptosis can enhance the sheets efficacy for treating heart failure after acute and chronic myocardial infarction. Furthermore, we show that myoblast sheets can serve as vehicles for delivery of growth factors, and induce therapeutic angiogenesis in the chronically ischemic heart. Finally, myoblasts induce, in a paracine manner, a cardiomyocyte-protective response against oxidative stress. Our study elucidates novel mechanisms of myoblast transplantation therapy, and suggests effective means to improve this therapy for the benefit of the heart failure patient.Sydämen vajaatoiminta on yleinen ja vakava etenevä oireyhtymä, johon liittyy korkea kuolleisuus. Sydämen vajaatoiminnan esiintyvyys on koko väestössä 1-2%, mutta yli 65-vuotiailla jopa 10%. Näin ollen väestön ikääntyessä myös sydämen vajaatoiminta yleistyy. Nykyiset hoitomuodot auttavat potilaita hidastamalla oireyhtymän etenemistä, mutta eivät vaikuta usein oireiden taustalla olevaan sydänlihassolujen määrän vähenemiseen. Soluviljelyssä kasvatetuista, erilaistumattomista luurankolihassoluista (myoblasteista) tehty solulauttasiirre on uusi lupaava hoitomuoto menetettyjen sydänlihassolujen uudistamiseksi. Solulautta voidaan siirtää sepelvaltimon ohitusleikkauksen yhteydessä vajaatoimintaisen sydämen pinnalle. Solusiirteessä tapahtuva solukuolema kuitenkin rajoittaa hoidon tehoa. Tutkimuksessa selvitettiin myoblastilauttojen hoidollista vastetta kokeellisessa sydäninfarktin jälkeisessä vajaatoimintamallissa. Solusiirteen selviytymistä sydämen pinnalla parannettiin ilmentämällä lautassa joko solukuolemaa estävää bcl2-geeniä tai uudisversuonitusta lisäävää hepatosyyttikasvutekijää. Lauttahoito annettiin heti sydäninfarktin jälkeen tai siitä 4 viikon kuluttua. Sydämen toimintaa arvioitiin kaikukardiografialla. Uudisverisuonitusta ja arpeutumista mitattiin kudosleikevärjäyksillä. Lisäksi myoblastilauttojen geeni-ilmentymistä ja sydänlihassolujen solukuolemaa tutkittiin soluviljelmissä. Solukuolemaa estävää bcl2:a ilmentävät myoblastilautat selviytyivät pidempään sydämessä infarktin jälkeen ja paransivat sydämen toimintaa. Hoidon vaikutus välittyi todennäköisesti lautan solujen erittämien liukoisten sydäntä suojaavien tekijöiden kautta. Myoblastilautoissa ilmennetty hepatosyyttikasvutekijä lisäsi uudisverisuonitusta, mutta ei parantanut sydämen toimintaa. Tutkimuksen tulokset paljastavat, että myoblastilauttojen hoidollista vastetta voidaan parantaa sydämen vajaatoiminnassa estämällä niiden solukuolemaa. Tutkimuksen tuloksia tullaan hyödyntämään kehitettäessä sydämen vajaatoimintapotilaiden kantasoluhoitoja

Imaging of moisture content in wood using electrical capacitance tomography

http://shop.tuverlag.at/de/the-world-conference-on-timber-engineeringThe current study investigates whether an electrical imaging modality, electrical capacitance tomography (ECT), could provide information on the moisture content in wood. In ECT, a set of electrodes are placed around the surface of the object, and based on electrical capacitance measurements from the surface, the spatial distribution of the electrical permittivity inside the object is reconstructed. In this experimental study, water is infiltrated in a wood sample for 7 days, and ECT measurements are sequentially collected during the absorption of water. The reconstructed ECT images show a constant increase of electrical permittivity in the location of water absorption. The results support the feasibility of ECT for imaging the water content in wood.Peer reviewe

Advances in Cell Transplantation Therapy for Diseased Myocardium

Peer reviewe

Mitochondrial respiratory dysfunction due to the conversion of substituted cathinones to methylbenzamides in SH-SY5Y cells

The increased use of cathinone-type designer drugs, known as legal highs, has led to concerns about their potential neurotoxicity due to their similarity to methamphetamine (METH). Therefore, closer investigations of their toxic effects are needed. We investigated the effects of the cathinones 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxymethcathinone (MDMC) and the amphetamine METH on cytotoxicity and mitochondrial respiration in SH-SY5Y neuroblastoma cells. We also investigated the contribution of reactive species, dopamine, Bcl-2 and tumor necrosis factor alpha(TNF alpha) on toxicity. Finally, we investigated the effect of cathinone breakdown products using ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry and studied their involvement in toxicity. We observed dose-dependent increases in cytotoxicity and decreases in mitochondrial respiration following treatment with all cathinones and amphetamines. Glutathione depletion increases amphetamine, but not cathinone toxicity. Bcl-2 and TNF alpha pathways are involved in toxicity but dopamine levels are not. We also show that cathinones, but not amphetamines, spontaneously produce reactive species and cytotoxic methylbenzamide breakdown products when in aqueous solution. These results provide an important first insight into the mechanisms of cathinone cytotoxicity and pave the way for further studies on cathinone toxicity in vivo.Peer reviewe

Comparison of Arrhythmogenicity and Proinflammatory Activity Induced by Intramyocardial or Epicardial Myoblast Sheet Delivery in a Rat Model of Ischemic Heart Failure

Although cell therapy of the failing heart by intramyocardial injections of myoblasts to results in regenerative benefit, it has also been associated with undesired and prospectively fatal arrhythmias. We hypothesized that intramyocardial injections of myoblasts could enhance inflammatory reactivity and facilitate electrical cardiac abnormalities that can be reduced by epicardial myoblast sheet delivery. In a rat model of ischemic heart failure, myoblast therapy either by intramyocardial injections or epicardial cell sheets was given 2 weeks after occlusion of the coronary artery. Ventricular premature contractions (VPCs) were assessed, using an implanted three-lead electrocardiograph at 1, 7, and 14 days after therapy, and 16-point epicardial electropotential mapping (EEPM) was used to evaluate ventricular arrhythmogenicity under isoproterenol stress. Cardiac functioning was assessed by echocardiography. Both transplantation groups showed therapeutic benefit over sham therapy. However, VPCs were more frequent in the Injection group on day 1 and day 14 after therapy than in animals receiving epicardial or sham therapy (p <0.05 and p <0.01, respectively). EEPM under isoproterenol stress showed macroreentry at the infarct border area, leading to ventricular tachycardias in the Injection group, but not in the myoblast sheet- or sham-treated groups (p = 0.045). Both transplantation types modified the myocardial cytokine expression profile. In animals receiving epicardial myoblast therapy, selective reductions in the expressions of interferon gamma, interleukin (IL)-1 beta and IL12 were observed, accompanied by reduced infiltration of inflammatory CD11b- and CD68-positive leukocytes, compared with animals receiving myoblasts as intramyocardial injections. Intramyocardial myoblast delivery was associated with enhanced inflammatory and immunomodulatory reactivity and increased frequency of VPCs. In comparison to intramyocardial injection, the epicardial route may serve as the preferred method of skeletal myoblast transplantation to treat heart failure.Peer reviewe

hHGF Overexpression in Myoblast Sheets Enhances Their Angiogenic Potential in Rat Chronic Heart Failure

Peer reviewe

K-kauppiaiden toiminta Facebookissa

Opinnäytetyöni aiheena on K-kauppiaiden toiminta Facebookissa. Työn toimeksiantajana on K-kauppiasliitto. Aiheen valintaan vaikutti oma mielenkiintoni vähittäiskauppaa ja sosiaalista mediaa kohtaan sekä se, että K-kauppiaiden toiminnasta Facebookissa ei aiemmin tiedetty paljoakaan. Teoriaosuudessa käsitellään ensin yritysviestinnän muutosta. Sosiaalisen median osalta käsitellään sen määritelmää ja hyödyntämistä suomalaisissa yrityksissä. Tarkemmin paneudutaan Facebookiin, viestintään siellä sekä sen yrityksille tarjoamiin mahdollisuuksiin ja uhkiin. Tutkimusosuudessa tutkitaan sitä, kuinka paljon K-kauppiaat hyödyntävät Facebookia kaupan toiminnassa ja millä tavalla sitä hyödynnetään. Teoriaosuuden ja tutkimusten jälkeen esitetään toimenpiteitä, joiden avulla K-kauppias voi hyödyntää Facebookia toiminnassaan. Työn tarkoituksena on antaa K-kauppiaille eväitä kehittää omaa toimintaansa Facebookissa. Työssä tarjotaan selkeitä ohjeita Facebookin hyödyntämiseen kauppiasvetoisen vähittäiskaupan liiketoiminnassa.In this thesis, I study the operations of Finnish K-Group retailers on Facebook. The thesis was commissioned by the Association of K-Retailers. My choice of subject was influenced by my personal interest in retailing and social media. The fact that there is little previous research and knowledge on the ways in which managers of K-stores use Facebook also contributed to my selection of this topic. In the theory part, I begin by focusing on recent changes in corporate communications. Next, I discuss the definition of social media and the ways in which Finnish businesses have utilized them. I pay particular attention to communicating through Facebook, the possibilities Facebook offers and the potential threats it presents. In the research part, I study how much managers of K-stores use Facebook for communicating with their clients about the store and in what ways it is used. The theory and the research sections are followed by a presentation of steps that a manager of a K-retail store can take to utilize Facebook in its operations. The objective of the study is to give retailers of K-stores a possibility to develop their ways of operating on Facebook. The study provides specific advice on making use of Facebook in the operations of a retail business that is driven by individual store managers