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.

Dokumentation och beskrivning som språkplanering : perspektiv från arbete med tre tecknade minoritetsspråk

Language Documentation and Description as Language Planning Working with Three Signed Minority Languages Sign languages are minority languages that typically have a low status in society. Language planning has traditionally been controlled from outside the sign-language community. Even though signed languages lack a written form, dictionaries have played an important role in language description and as tools in foreign language learning. The background to the present study on sign language documentation and description as language planning is empirical research in three dictionary projects in Finland-Swedish Sign Language, Albanian Sign Language, and Kosovar Sign Language. The study consists of an introductory article and five detailed studies which address language planning from different perspectives. The theoretical basis of the study is sociocultural linguistics. The research methods used were participant observation, interviews, focus group discussions, and document analysis. The primary research questions are the following: (1) What is the role of dictionary and lexicographic work in language planning, in research on undocumented signed language, and in relation to the language community as such? (2) What factors are particular challenges in the documentation of a sign language and should therefore be given special attention during lexicographic work? (3) Is a conventional dictionary a valid tool for describing an undocumented sign language? The results indicate that lexicographic work has a central part to play in language documentation, both as part of basic research on undocumented sign languages and for status planning. Existing dictionary work has contributed new knowledge about the languages and the language communities. The lexicographic work adds to the linguistic advocacy work done by the community itself with the aim of vitalizing the language, empowering the community, receiving governmental recognition for the language, and improving the linguistic (human) rights of the language users. The history of signed languages as low status languages has consequences for language planning and lexicography. One challenge that the study discusses is the relationship between the sign-language community and the hearing sign linguist. In order to make it possible for the community itself to take the lead in a language planning process, raising linguistic awareness within the community is crucial. The results give rise to questions of whether lexicographic work is of more importance for status planning than for corpus planning. A conventional dictionary as a tool for describing an undocumented sign language is criticised. The study discusses differences between signed and spoken/written languages that are challenging for lexicographic presentations. Alternative electronic lexicographic approaches including both lexicon and grammar are also discussed. Keywords: sign language, Finland-Swedish Sign Language, Albanian Sign Language, Kosovar Sign Language, language documentation and description, language planning, lexicography

Histochemical investigations on the interrenal system of the brook lamprey (Lapetra planeri Bloch). [Translation from: Acta biol.med.germ. 24, 553-554, 1970. ]

Histochemical experiments are conducted in order to study the interrenal cells of European brook lamprey (Lampetra planeri).

Influence of carbon tetrachloride on the liver of tadpoles of brown frog (Rana temporaria) [Translation from: Trudy leningt.sanit.-gig.med.Inst. 82, 32-36, 1967]

Comparative studies of the structure and regeneration of tissues in different vertebrates make it possible to get ideas from the evolution and regeneration potential of tissues. In this study are considered the reactive changes in the liver of larvae of the amphibian Rana temporaria to CC14 of different concentrations. Tadpoles of different sizes and different growth were placed once each day every day in a vessel with a determined solution of CC14 in water. The liver of tadpoles has a distinctive structure. It is distinguished by structure not only from the liver of higher vertebrates, but also from the liver of the adult frogs. The liver of the latter has an insignificant amount of fat and a whole series of other characters not typical of the liver of the tadpole. Placing the tadpoles in a solution of CCl4 with a concentration of 0.1% did not produce in the liver noticeable morphological changes. The author concludes that the absence of degenerative changes in the liver tadpoles, in spite of a high percentage of death of the experimental animals, tells of the well-known resistance of their liver to the influence of CC14.

‘Med Hondo’s Sarraounia: The musical articulation of cultural transformation’

This article examines music in Med Hondo’s Sarraounia, considering how it contributes to the dramatic form of the movie while concurrently articulating narratives regarding cultural transformation through both its extrinsic (cultural) and intrinsic (formal) dimensions. Examining how the use of traditional and contemporary African music politicises diegetic space by referring us to the relationships between indigenous musical forms and their global, culturally hybrid descendents, it then demonstrates the complex manner in which the film uses the formal specificities of African and Western musical idioms to articulate a narrative regarding the cultural transformations that occur when an oral culture (Africa) encounters a literate, modernised culture (the West).