Search

Background: Artemisinin-based combinations currently recommended for treatment of uncomplicated Plasmodium falciparum malaria in many countries of sub-Saharan Africa are substrates of CYP enzymes. The cytochrome enzyme system is responsible for metabolism of about 80-90% of clinically used drugs. It is, therefore, important to obtain the pharmacogenetics of the population in the region with respect to these combinations and thereby enable practitioners to predict treatment outcomes. The aim of this study was to detect and determine allelic frequencies of CYP2C8*2, CYP2C8*3, CYP3A4*1B, CYP3A5*3 and CYP2B6*6 variant alleles in a Tanzanian indigenous population. Methods: Genomic DNA extraction from blood obtained from 256 participants who escorted patients at Karume Health Centre in Mwanza Tanzania, was carried out using the Gene JET (TM) Genomic DNA purification kit (Thermo Scientific). Genotyping for the cytochrome P450 variant alleles was performed using predesigned primers. Amplification was done by PCR while differentiation between alleles was done by restriction fragment length polymorphism (PCR-RFLP) (for CYP2C8*2, CYP2C8*3) and sequencing (for CYP2B6*6, CYP3A5*3 and CYP3A4*1B). Results: CYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A4*1B and CYP2B6*6 variant allelic frequencies were found to be 19,10,16,78 and 36% respectively. Conclusion: Prevalence of CYP2C8*2, CYP3A5*3, CYP3A4*1B and CYP2B6*6 mutations in a Tanzanian population/ subjects are common. The impact of these point mutations on the metabolism of anti-malarial drugs, particularly artemisinin-based combinations, and their potential drug-drug interactions (DDIs) needs to be further evaluated.

HIV/AIDS förekommer globalt men få studier fokuserar på hur patienter i Europa och Nordamerika upplever mötet med hälso- och sjukvården. Syftet med denna studie var att belysa hur patienter med HIV/AIDS uppfattar att de blir bemötta inom hälso- och sjukvården i Europa och Nordamerika. En systematisk litteraturgenomgång genomfördes. Det framkom att HIV/AIDS-patienter i dessa delar av världen upplevde stigmatisering i mötet med vården. Detta ledde till ett minskat välbefinnande och lägre grad av tillfredsställelse med hälso- och sjukvården. Fem teman utkristalliserades relaterade till bemötande från hälso- och sjukvårdspersonalen: oprofessionellt bemötande, särbehandling, försummelse, rädsla relaterat till kunskapsbrist samt specialiserade kliniker. Insatser behövs för att säkerställa att dessa patienter får ett respektfullt bemötande och vård på lika villkor. Detta kan förverkligas genom utbyggnad av specialistvården. Vidare forskning inom ämnet kan ta avstamp i denna litteraturstudie.

The establishment of green areas in urban environment for ecological sustainability is a strategy recognized in academics as well as in politics and governance. This thesis investigates how and to what extent various measures and interventions of increased urban green areas and their ecological benefits may contribute to ecological sustainability and improve urban life quality. In addition to a literature review of topic this thesis also contains an applied study of the new construction project “Södra Nyhamnen” in Malmö. The study shows that measures and interventions to increase urban green areas can contribute to locally enhanced biodiversity, possible better air quality, infiltration of storm water and retainment of storm water contaminations in soil instead of polluting of receiving waters. Shading, less heat radiation and wind protection, will also regulate the local climate. The study further shows that measures for urban green areas contributes to improvement of local urban environment, although it should primarily be described as environmental health improvement and only secondly as ecologically sustainable, as the measures consist of reducing or remediating measures with environmental health focus.

Problem: Dagens fragmentariska samhälle har ökat vikten och samtidigt försvårat kommunikationen av organisationsidentitet. Uppsatsen tar ett brett grepp om den problematiken genom att sammanföra förståelsen av tre fält, kommunikation, berättelser och identitet då dessa är tydligt interrelaterade men inte tillräckligt belysta i förhållande till varandra, och särskilt i relation till kommunikationen av organisationsidentitet. Syfte: Att belysa organisationsidentitet ur ett narrativt och kommunikativt perspektiv för att bringa insikter kring kommunikationen av identitet i organisationer och därigenom öka kunskapen om hur berättelser kan användas för att analysera kommunikationen och konstruktion av identitet. Metod: En fallstudie av Svenska institutet, inkluderande kvalitativ dokumentanalys och kvalitativa intervjuer med sju organisationsmedlemmar. Slutsatser: Ett fokus på berättelser ger komplexa insikter kring konstruktionen och kommunikationen av organisationsidentitet och visar hur plurala meningsskapande processer kan belysas på flera nivåer och ur olika perspektiv.

Thyroid hormone (TH) deficiency during development causes severe and permanent neuronal damage, but the primary insult at the tissue level has remained unsolved. We have defined locomotor deficiencies in mice caused by a mutant thyroid hormone receptor alpha 1 (TR alpha 1) with potent aporeceptor activity attributable to reduced affinity to TH. This allowed identification of distinct functions that required either maternal supply of TH during early embryonic development or sufficient innate levels of hormone during late fetal development. In both instances, continued exposure to high levels of TH after birth and throughout life was needed. The hormonal dependencies correlated with severely delayed appearance of parvalbumin-immunoreactive GABAergic interneurons and increased numbers of calretinin-immunoreactive cells in the neocortex. This resulted in reduced numbers of fast spiking interneurons and defects in cortical network activity. The identification of locomotor deficiencies caused by insufficient supply of TH during fetal/perinatal development and their correlation with subtype-specific interneurons suggest a previously unknown basis for the neuronal consequences of endemic cretinism and untreated congenital hypothyroidism, and specifies TR alpha 1 as the receptor isoform mediating these effects.

Denna uppsats behandlar det legala arbetstagarinflytandet i svenska privat-ägda bolag vid en bolagisering. De rättsregler som normalt är tillämpliga vad gäller inflytande i relationen mellan arbetsgivare och arbetstagare pre­senteras, samt deras tillämplighet i och inför en bolagiseringssituation. Även möjligheterna att göra dessa tillämpliga genom ett mer flexibelt arbetsgivar­begrepp än det formella arbetsgivarbegreppet behandlas. I syfte att ge en något mer nyanserad bild av förutsättningarna för arbetstagarinflytandet ges även exempel på regler som återfinns i folkrättsliga överenskommelser och medbestämmandeavtal. Regler som i vissa fall ligger utanför området av gällande svensk arbetsrätt. De svenska lagar och regler som ger arbetstagare rätt till inflytande grun­dar sig i de flesta fall på rättigheter och skyldigheter för den formella arbetsgivaren å ena sidan och arbetstagarorganisation med vilken denne har tecknat kollektivavtal å den andra. Arbetsgivare är den fysiska eller juri­diska person hos vilken en arbetstagare är anställd, vilket ska anges i ingånget anställningsavtal. Om det i praktiken är ett annat bolag som fattar besluten finns det i princip ingen rätt att förhandla med detta. Det finns dock exempel på fall då ett moderbolag gjorts ansvarig efter att ha fattat beslut om att utlämna arbete, för sin egen räkning, via ett kommissionärsföretag utan att först förhandla med sina anställda. Ett undantag till att rätten för inflytande och information stannar vid bo­lagsgränsen finns i rätten till styrelserepresentation, vilken kan ge arbetsta­garna rätt till representation i moderbolagets styrelse. Detta förutsätter dock att moderbolaget är svenskt. Arbetstagarrepresentanter omfattas av tyst­nadsplikt i känsliga frågor, en tystnadsplikt som även gäller gentemot arbetstagarorganisationen de representerar. Medbestämmandeavtal kan ge rätt till arbetstagarinflytande i koncerner och därmed också vid bolagise­ringar. För att stärka arbetstagarnas möjlighet a

Lack of sufficient thyroid hormone during pregnancy and early postnatal development results in profound mental retardation and motor deficits whereas altered thyroid status in the adult is associated with disturbed metabolic homeostasis and impaired cardiac function. Thyroid hormone mediates its effects through the distinct thyroid hormone receptors (TR) TRalpha1 and TRbeta1-2, which are ligand-modulated transcription factors that regulate gene expression both in the presence and absence of hormone. Mutations in the TRbeta gene that decrease affinity to ligand are associated with the well known syndrome Resistance to thyroid hormone (RTH), which is characterized by elevated circulating levels of thyroid hormone and a mixed hyper- and hypothyroid phenotype. However, no patient with a corresponding mutation in the TRalpha gene has been found. In this thesis, I describe the developmental and physiological consequences of a point mutation introduced into the mouse TRalpha1 gene. The mutation, originally identified in TRbeta (R438C) of RTH patients, reduces affinity for T3 10-fold, and causes the receptor to act as an aporeceptor unless challenged with high levels of thyroid hormone. We report that mice heterozygous for this mutation (TRalpha1+m mice) exhibit locomotor dysfunctions caused by insufficient supply of thyroid hormone during fetal/postnatal development. Furthermore, treatment with thyroid hormone during specific stages of development ameliorated these deficiencies. The locomotor dysfunctions correlated with delayed or perturbed development of several brain regions. Notably, we report that specific GABAergic cells in the neocortex were affected: the appearance of parvalbumin-immunoreactive GABAergic interneurons was severely delayed whereas the numbers of calretinin-immunoreactive cells were increased. The TRalpha1+m mice also exhibited increased metabolic rate, hyperphagia and resistance to obesity despite their reduced body temperature. This is likely due to

Thyroid hormone (TH) deficiency during development causes severe and permanent neuronal damage, but the primary insult at the tissue level has remained unsolved. We have defined locomotor deficiencies in mice caused by a mutant thyroid hormone receptor alpha1 (TR alpha1) with potent aporeceptor activity attributable to reduced affinity to TH. This allowed identification of distinct functions that required either maternal supply of TH during early embryonic development or sufficient innate levels of hormone during late fetal development. In both instances, continued exposure to high levels of TH after birth and throughout life was needed. The hormonal dependencies correlated with severely delayed appearance of parvalbumin-immunoreactive GABAergic interneurons and increased numbers of calretinin-immunoreactive cells in the neocortex. This resulted in reduced numbers of fast spiking interneurons and defects in cortical network activity. The identification of locomotor deficiencies caused by insufficient supply of TH during fetal/perinatal development and their correlation with subtype-specific interneurons suggest a previously unknown basis for the neuronal consequences of endemic cretinism and untreated congenital hypothyroidism, and specifies TR alpha1 as the receptor isoform mediating these effects.

In this study, a significant increase by 50% in intracellular free calcium concentration ([Ca(2+)](i)) was observed in differentiated human neuroblastoma (SH-SY5Y) cells after exposure to 0.25microM of the fungal metabolite gliotoxin for 72h. Further, the involvement of caspases and calpains was demonstrated to underlie the gliotoxin-induced cytotoxic and neurite degenerative effects. The caspase inhibitor Z-VAD-fmk almost completely reduced the neurite degeneration from 40% degeneration of neurites to 5% as compared to control. Inhibition of calpains with calpeptin significantly attenuated gliotoxin-induced cytotoxicity, determined as reduction in total cellular protein content, from 43% to 14% as compared to control cells. Western blot analyses of alphaII-spectrin breakdown fragments confirmed activity of the proteases, and that alphaII-spectrin was cleaved by caspases in gliotoxin-exposed cells. These results show that calpains and caspases have a role in the toxicity of gliotoxin in differentiated SH-SY5Y cells and that the process may be Ca(2+)-mediated.