Diabetic cardiomyopathy and post-infarct ventricular remodelling : Effects of levosimendan in a rodent model of type II diabetes

Type 2 diabetes is a risk factor for the development of cardiovascular disease. Recently, the term diabetic cardiomyopathy has been proposed to describe the changes in the heart that occur in response to chronic hyperglycemia and insulin resistance. Ventricular remodelling in diabetic cardiomyopathy includes left ventricular hypertrophy, increased interstitial fibrosis, apoptosis and diastolic dysfunction. Mechanisms behind these changes are increased oxidative stress and renin-angiotensin system activation. The diabetic Goto-Kakizaki rat is a non-obese model of type 2 diabetes that exhibits defective insulin signalling. Recently two interconnected stress response pathways have been discovered that link insulin signalling, longevity, apoptosis and cardiomyocyte hypertrophy. The insulin-receptor PI3K/Ak pathway inhibits proapoptotic FOXO3a in response to insulin signalling and the nuclear Sirt1 deacetylase inhibits proapoptotic p53 and modulates FOXO3a in favour of survival and growth. --- Levosimendan is a calcium sensitizing agent used for the management of acute decompensated heart failure. Levosimendan acts as a positive inotrope by sensitizing cardiac troponin C to calcium and exerts vasodilation by opening mitochondrial and sarcolemmal ATP-sensitive potassium channels. Levosimendan has been described to have beneficial effects in ventricular remodelling after myocardial infarction. The aims of the study were to characterize whether diabetic cardiomyopathy associates with cardiac dysfunction, cardiomyocyte apoptosis, hypertrophy and fibrosis in spontaneously diabetic Goto-Kakizaki (GK) rats, which were used to model type 2 diabetes. Protein expression and activation of the Akt FOXO3a and Sirt1 p53 pathways were examined in the development of ventricular remodelling in GK rats with and without myocardial infarction (MI). The third and fourth studies examined the effects of levosimendan on ventricular remodelling and gene expression in post-MI GK rats. The results demonstrated that diabetic GK rats develop both modest hypertension and features similar to diabetic cardiomyopathy including cardiac dysfunction, LV hypertrophy and fibrosis and increased apoptotic signalling. MI induced a sustained increase in cardiomyocyte apoptosis in GK rats together with aggravated LV hypertrophy and fibrosis. The GK rat myocardium exhibited decreased Akt- FOXO3a phosphorylation and increased nuclear translocation of FOXO3a and overproduction of the Sirt1 protein. Treatment with levosimendan decreased cardiomyocyte apoptosis, senescence and LV hypertrophy and altered the gene expression profile in GK rat myocardium. The findings indicate that impaired cardioprotection via Akt FOXO3a and p38 MAPK is associated with increased apoptosis, whereas Sirt1 functions in counteracting apoptosis and the development of LV hypertrophy in the GK rat myocardium. Overall, levosimendan treatment protects against post-MI ventricular remodelling and alters the gene expression profile in the GK rat myocardium.

Vastasyntyneen varsan sepsis osa II - Infektion diagnosoiminen, aiheuttajamikrobit ja mikrobilääkeresistenssi

Sepsis eli infektion aiheuttama yleistynyt tulehdusreaktio on merkittävä kuolleisuuden aiheuttaja vastasyntyneillä varsoilla. Kirjallisuuskatsauksessa on käsitelty sepsiksen patofysiologiaa ja kliinisiä oireita vastasyntyneillä varsoilla sekä sepsikselle altistavia tekijöitä. Vastasyntyneen varsan sepsiksen diagnosoimisessa kliinisten oireiden arvioinnilla on keskeinen merkitys sairauden varhaisessa tunnistamisessa ja hoidon aloittamisessa. Sairauden nopean etenemisen ja veriviljelytulosten hitaan valmistumisen vuoksi antibioottihoito joudutaan aloittamaan jo ennen viljelytulosten valmistumista. Veriviljelyllä on kuitenkin tärkeä merkitys sepsisdiagnoosin ja valitun antibioottihoidon varmistamisessa. Sairaalakohtaisten veriviljelynäytetulosten seuranta mahdollistaa ensisijaisen mikrobilääkkeen valinnan aiemmin eristettyjen aiheuttajamikrobien esiintyvyyden ja mikrobilääkeherkkyyksien perusteella. Yleisimpiä vastasyntyneen varsan sepsiksen aiheuttajia ovat kirjallisuuden mukaan suolistoperäiset gram-negatiiviset bakteerit. Escherichia colin osuus vastasyntyneiltä varsoilta otetuista veriviljelynäytteistä eristetyistä bakteerikannoista on vaihdellut eri tutkimuksissa 18,7 - 50,0 %. Pohjois-Amerikassa tehdyissä tutkimuksissa varsojen veriviljelynäytteistä eristettyjen E.coli -kantojen herkkyys yleisesti käytetylle trimetopriimi-sulfadiatsiinille on ollut huono (57–71 %). Penisilliinin ja gentamisiinin yhdistelmälle enterobakteerien herkkyyden on raportoitu olevan hyvä. Suomessa tilanteen on arvioitu olevan parempi. Tutkimuksessa kartoitettiin retrospektiivisesti veriviljelyn käyttöä varsojen sepsiksen diagnostiikassa, sepsiksen aiheuttajamikrobien esiintymistä ja mikrobilääkkeiden käyttöä Yliopistollisessa eläinsairaalassa (YES) vuosina 2004–2006. Tutkimusaineisto koostuu yhteensä 90 korkeintaan 10 päivän ikäisenä YES:aan tuodun varsan potilastiedoista. Sairaalaan saapuneista varsoista 30 % oli otettu veriviljelynäyte. Veriviljelynäytteistä positiivisia oli 62,5 %. 60 % positiivisista näytteistä kasvoi vähintään kahta bakteerilajia. Yleisin aiheuttajabakteeri oli Escherichia coli (23,1 %). Yksi eristetyistä E.coli -kannoista oli resistentti ampisilliinille, gentamisiinille ja trimetopriimi-sulfadiatsiinille. Aineiston pienen koon vuoksi tutkimus ei kuitenkaan anna luotettavaa kuvaa eristettyjen aiheuttajamikrobien mikrobilääkeherkkyydestä laajemmin. Sekakasvujen osuus oli suuri ja tyypillisten veriviljelynäytteitä kontaminoivien bakteerilajien (Streptococcus viridans sp., Micrococcus sp., koagulaasinegatiiviset stafylokokit) osuus oli yli 30 % eristetyistä bakteerikannoista. Tämä viittaa ongelmiin veriviljelynäytteenottotekniikassa riittävän aseptiikan saavuttamien osalta. Koagulaasinegatiiviset stafylokokit voivat myös aiheuttaa sepsiksen, mutta niiden merkitys vastasyntyneiden varsojen sepsiksen aiheuttajina on epäselvä.

Cattle Teeth in Graves : Interpretations of animal bones found in Finnish inhumation graves (ca AD 550-1700)

The nature of a burial is always ritualistic. This is often forgotten when dealing with Finnish inhumation burials containing animal bones. Only the animal bones found close to the deceased have traditionally been thought to have a ritualistic purpose. The animal bones found in the filling of the grave, which is still part of the burial, has on the other hand, often been neglected in the previous research. In this Master s thesis I will discuss the function and interpretation of animal bones in graves. The base of this study is six sites, all of different nature, from Finland. Luistari in Eura is from the western coast and is dated to Late Iron Age (and possibly Medieval period), the Medieval hamlet of Finno is situated in Espoo which is situated on the southern coast. Two town burials, Turku and Porvoo, are also included in this study. The graves from Turku are dated to Late Medieval period and Early Renaissance, whereas the cemetery in Porvoo is from the 18th century. Visulahti in Mikkeli is from the Late Iron Age and represents Eastern Finnish burial tradition, the same as Suotniemi from Käkisalmi parish, which is nowadays part of Russia. While parts of the animal bones had already been analysed before, the author also analysed animal bones for the purpose of the present Master´s thesis. The bones were compared to the burial contexts, when possible. Based on the comparisons I have made interpretations which might explain the existence of animal bones in the graves. The interpretations are among others sacrifice, commemoration meals and animal burials. The site could also have been a settlement site prior to the graves, thus the bones in the graves would belong to the settlement phase. When comparing the date of the studied sites, the town burials are later and the animal bones are probably related to previous or contemporary use of the sites as graveyards. On top of this there does not seem to be much difference in burial tradition between Eastern and Western Finland, although at least from the hamlet burials of Finno there are aspects that could be linked to Eastern burials. In making the interpretations I have taken into consideration the aspects of belief during different time periods when they could be accounted as relevant. Also the problems with bone preservation were relevant and challenging for the study. Often only the hardest substance of the skeleton, namely teeth, has been preserved. For this reason the quality of the archaeological documentation was a key issue in this study. In producing quality interpretations of the animal bones in graves, the bones, contexts and their relationship to the surrounding site should be documented with care.

Private and municipal forests and the forestry planning system in Japan - trends and problems after World War II.

XVIII IUFRO World Congress, Ljubljana 1986.

Search for the Higgs boson in the all-hadronic final state using the CDF II detector

We report on a search for the production of the Higgs boson decaying to two bottom quarks accompanied by two additional quarks. The data sample used corresponds to an integrated luminosity of approximately 4  fb-1 of pp̅ collisions at √s=1.96  TeV recorded by the CDF II experiment. This search includes twice the integrated luminosity of the previous published result, uses analysis techniques to distinguish jets originating from light flavor quarks and those from gluon radiation, and adds sensitivity to a Higgs boson produced by vector boson fusion. We find no evidence of the Higgs boson and place limits on the Higgs boson production cross section for Higgs boson masses between 100  GeV/c2 and 150  GeV/c2 at the 95% confidence level. For a Higgs boson mass of 120  GeV/c2, the observed (expected) limit is 10.5 (20.0) times the predicted standard model cross section.