Hypertension, kardiotoxicitet och njursvikt i samband med tyrosinkinashämmaren sunitinib

Nybildning av blodkärl från tidigare existerande kärl, angiogenes, är ett väsentligt skede vid tumörtillväxt. Denna process regleras av bland annat tillväxtfaktorer, var av den vaskulära endoteliala tillväxtfaktorn har en central roll. Hämning av angiogenes kan ske antingen extracellulärt med hjälp av humaniserade monoklonala antikroppar eller intracellulärt med hjälp av småmolekylära hämmaren. Sunitinib är en småmolekylär multikinashämmare och inhiberar flera tyrosinkinasreceptorer som påverkar tumörtillväxten och metastasutvecklingen vid cancer. Sunitinibs främsta indikationer är gastrointestinala stromacellstumörer, metastaserad njurcellscancer och neuroendokrina tumörer i bukspottskörteln. Behandling med tyrosinkinashämmare orsakar biverkningar som hypertension, kardiotoxicitet och njursvikt, vilka antas bero på de hämmande effekterna på mål som inte är väsentliga för anti-cancer-aktiviteten (”off-target” biverkningar). Bland annat AMP-aktiverat proteinkinas (AMPK), ett kinas som upprätthåller metabolisk homeostas i hjärtat, inhiberas av sunitinib och antas framkalla kardiovaskulära biverkningar. För att reducera ”off-target” biverkningar strävar man till att hitta alternativ som minskar de skadliga effekterna utan att den terapeutiska aktiviteten försvagas. Bland annat ett begränsat kaloriintag har uppvisat skyddande effekt på hjärtat via mekanismer sammankopplade till ökad resistens mot oxidativ stress, inflammation och mitokondriell dysfunktion, samt avtagande apoptos och autofagi. Detta sker delvis genom aktivering av enzymet Sirt1. Syftet med den här studien var att undersöka ifall kaloribegränsning skyddar mot kardiovaskulära och renala biverkningar inducerade av sunitinib hos råttor. Dessutom studerades vilka signalkedjor i cellen som medverkar. I studien användes 40 spontant hypertensiva råttor samt 10 normotensiva Wistar-Kyoto råttor. Försöksdjuren delades in i fem grupper beroende på behandling; I WKY kontroll, II SHR kontroll, III SHR + kaloribegränsning 70 %, IV SHR + sunitinib 3 mg/kg och V SHR + sunitinib 3 mg/kg + kaloribegränsning 70 %. Behandlingsperioden var åtta veckor. Blodtrycket mättes varje vecka med svansmanchett, urinutsöndringen undersöktes vecka 4 och vecka 8 med metabolismburar, ultraljudsundersökning av hjärtat utfördes sista veckan och blodkärlens respons till acetylkolin och natriumnitroprussid studerades i samband med avlivning. Proteinerna Sirt1 och AMPK analyserades i hjärtat med Western blotting samt förekomsten av makrofagmarkören ED1 i njurarna med immunhistokemi. Studien visade att sunitinibdosen 3 mg/kg är mycket väl tolererbar hos råttor eftersom sunitinib inte orsakade högre blodtryck, kraftigare hypertrofi eller mer omfattande njurskada jämfört med obehandlade SHR- grupper. Utgående från resultaten kan man också konstatera att kaloribegränsningen har positiva kardiovaskulära effekter.

Finlandismer och språkvård från 1800-talet till i dag

The aim of the study is to investigate the use of finlandisms in an historical perspective, how they have been viewed from the mid-19th century to this day, and the effect of language planning on their use. A finlandism is a word, a phrase, or a structure that is used only in the Swedish varieties used in Finland (i.e. in Finland Swedish), or used in these varieties in a different meaning than in the Swedish used in Sweden. Various aspects of Finland-Swedish language planning are discussed in relation to language planning generally; in addition, the relation of Finland Swedish to Standard Swedish and standard regional varieties is discussed, and various types of finlandisms are analysed in detail. A comprehensive picture is provided of the emergence and evolution of the ideology of language planning from the mid-19th century up until today. A theoretical model of corpus planning is presented and its effect on linguistic praxis described. One result of the study is that the belief among Finland-Swedish language planners that the Swedish language in Finland must not be allowed to become distanced from Standard Swedish, has been widely adopted by the average Finland Swede, particularly during the interwar period, following the publication of Hugo Bergroth s work Finlandssvenska in 1917. Criticism of this language-planning ideology started to appear in the 1950s, and intensified in the 1970s. However, language planning and the basis for this conception of language continue to enjoy strong support among Swedish-speaking Finns. I show that the editing of Finnish literary texts written in Swedish has often been somewhat amateurish and the results not always linguistically appropriate, and that Swedish publishers have in fact adopted a rather liberal attitude towards finlandisms. My conclusion is that language planning has achieved rather modest results in its resistance to finlandisms. Most of the finlandisms used in 1915 were still in use in 2005. Finlandisms occur among speakers of all ages, and even among academically educated people despite their more elevated style. The most common finlandisms were used by informants of all ages. The ones that are firmly rooted are the most established, in other words those that are stylistically neutral, seemingly genuinely Swedish, but which are nevertheless strongly supported by Finnish, and display a shift in meaning as compared with Standard Swedish.

Deutschland, Deutschland über alles : Tysk föreningsverksamhet i Finland och Sverige 1910-1950

The voluntary associations dealt with in this dissertation were ethnic clubs and societies promoting the interests of German immigrants in Finland and Sweden. The associations were founded at the end of the 19th century as well as at the beginning of the 20th century during a time in which migration was high, the civil society grew rapidly and nationalism flourished. The work includes over 70 different associations in Finland and Sweden with a number of members ranging from ten to at most 2, 500. The largest and most important associations were situated in Helsinki and Stockholm where also most of the German immigrants lived. The main aim of this work is to explore to what extent and how the changes in government in Germany during 1910 to 1950 were reflected in the structures and participants, financial resources and meeting places, networks and activities of the German associations in Finland and Sweden. The study also deals with how a collective German national identity was created within the German associations. The period between 1910 and 1950 has been described by Hobsbawm as the apogee of nationalism. Nationalism and transnationalism are therefore key elements in the work. Additionally the research deals with theories about associations, networking and identity. The analysis is mostly based on minutes of meetings, descriptions of festivities, annual reports and historical outlines about the associations. Archival sources from the German legations, the German Foreign Office, and Finnish and Swedish officials such as the police and the Foreign Offices are also used. The study shows that the collective national identity in the associations during the Weimar Republic mostly went back to the time of the Wilhelmine Empire. It is argued that this fact, the cultural propaganda and the aims of the Weimar Republic to strengthen the contacts between Germany and the German associations abroad, and the role of the German legations and envoys finally helped the small groups of NSDAP to infiltrate, systematically coordinate and finally centralize the German associational life in Finland and Sweden. The Gleichschaltung did not go as smoothly as the party wanted, though. There was a small but consistent opposition that continued to exist in Finland until 1941 and in Sweden until 1945. The collective national identity was displayed much more in Sweden than in Finland, where the associations kept a lower profile. The reasons for the profile differences can be found in the smaller number of German immigrants in Finland and the greater German propaganda in Sweden, but also in the Finnish association act from 1919 and the changes in it during the 1920s and 1930s. Finally, the research shows how the loss of two world wars influenced the associations. It argues that 1918 made the German associations more vulnerable to influence from Germany, whereas 1945 brought the associational life back to where it once started as welfare, recreational and school associations.

Notulae entomologicae. Årgång I vuosik.

Kielet ruotsi, englanti, latina, suomi, saksa.