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Browsing by master's degree program "none"

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  • Iivonen, Anna-Pauliina (2018)
    Recently, our group reported that mutations in KCNQ1, a potassium channel gene usually linked to long QT syndrome, cause growth hormone deficiency and maternally inherited gingival fibromatosis. Expression of the mutated KCNQ1 with KCNE2 subunit was shown to reduce pituitary hormone secretion in functional experiments in the original study. The aim of this thesis was to investigate if germline mutations in KCNQ1 and KCNE2, a gene encoding an auxiliary potassium channel subunit, could also play a role in the opposite phenomenon, growth hormone excess. Growth hormone (GH) excess causes acromegaly, a condition that is typically due to a GH secreting pituitary adenoma. I screened KCNQ1 and KCNE2 for germline mutations in 45 acromegaly patients by Sanger sequencing and predicted effects of the mutations on protein function by in silico tools. Only deep intronic and synonymous polymorphisms were detected in KCNQ1. These findings were likely insignificant based on the in silico predictions and the variants’ frequencies in the general population. In KCNE2, a heterozygous c.22A>G, p.(Thr8Ala) mutation with an unknown significance was found in two patients. It was present in the general population with a frequency of 0.0038. In conclusion, no evidence of KCNQ1 or KCNE2 mutations being associated with growth hormone excess was found. Mutation screenings of larger patient series and additional functional experiments are needed to shed more light on the roles of KCNQ1 related genes in growth hormone secretion.
  • Neuvonen, Janina (2019)
    Flowability of powders is in critical role when manufacturing the most popular dosage forms, tablets and capsules, of pharmaceutical industry. Re-formulation is expensive and time-consuming, so it is important to determine powder flow properties at the initial stage of drug development prior to tabletting and encapsulation processes. There are many different methods, like shear cell, flow through an orifice and bulk and tapped density, to examine powder flowability. Despite the methods, the most reliable means of examining powder flowability is often empirical. In early stages of drug development, it would be good to have faster, more reliable and cheaper methods to examine powder flowability. FT4 Powder Rheometer is a relatively new flowability characterization technique. The aim of this study is to find out whether the library created using the FT4 Powder Rheometer methods makes it possible to characterize the rheological properties of solids in the early stages of drug development. In addition, the aim is to investigate whether FT4 Powder Rheometer methods can predict the success of masses in tableting and encapsulation processes. The information gained from the research can be used in the future, for example, in continuous processes, because flowability plays an important role, especially in the supply of raw materials to the process, which is the most important division of continuous processes. To the library were selected for particle size and shape 15 different types of material. These materials were subjected to five different FT4 Powder Rheometer basic test methods. In addition, the particle size and shape of the materials and the flow through an orifice and the bulk and tapped density were determined to support the results of the powder rheometer. The principal component analysis was used to process the results. As the tablet and capsule masses examined, the masses of a previous study were utilized. Those masses were tableted and encapsulated in that previous study. These tablet and capsule masses contain a variable amount of cohesive drug substance. FT4 Powder Rheometer methods provide more complex information about materials and their behaviour than conventional flowability test methods. From the powder rheometer parameters pressure drop, compressibility and specific energy distinguish the cohesive and the non-cohesive materials, because the cohesive materials with these parameters obtain clearly higher values than non-cohesive materials. Additionally, the cohesion of FT4 Powder Rheometer shear cell test mainly distinguishes highly cohesive materials from other materials. The flow rate index makes it possible to separate the materials to which the change in flow rate particularly affects. Fluidizing materials, due to the air flow, are distinguished by the aeration test. Avicel PH-102 could be used as a rough limit value for well and poorly flowing materials in the created library (excluding the aeration and shear cell test). Stability index -, flow rate index -, specific energy -, pressure drop -, and compressibility-results of the FT4 Powder Rheometer correlated to the proportional proportion of the cohesive drug in the mixture. These parameters could possibly be used to distinguish mixtures containing the cohesive material. Additionally, specific energy, compressibility, pressure drop, basic flowability energy, stability index and flow rate index correlated with the weight variation of the tablets. With these parameters one could possibly assess the tabletability of the mixtures. A much larger library is needed to evaluate and predict the rheological properties of new materials. FT4 Powder Rheometer can possibly be used to predict the tableting success of tablet and capsule masses. This would be interesting to look more extensively, for example as part of a library. Additionally, it would be good to investigate whether the results of powder rheometer correlate to continuous production.
  • Talvio, Satu (2018)
    There are about 30 000 dogs in the city of Helsinki, the capital city of Finland. Dog excrements are destined eather on the communal waste system or in the city environment: in the streets, parks, beaches or forests. Dog droppings cause both a visible and smelly problem especially in the springtime when the snow melts. Nutrients and microbiological harmful substances run to the runoff waters, and the growing amount of dog excrements is engaging the communal waste management by collecting the manure and handling it. In this study the dog droppings were studied in four parks in the city of Helsinki. The droppings that were collected in the trash bins by the dog owners and the droppings that were left in the ground near the bins were weighted daily for twenty days in November- December 2017. The study was a quantitative field study, in which the weight of the droppings were weighted and the material of the excrement bag was registered. The study was divided in two parts. In the first part the amount of droppings that were left uncollected in to the intended bins was measured. In the other part the effect of dropping bag was estimated from the sewage handling and waste disposal point of view. The theoretical frame of reference was the analysis of environmental impacts of dogs, which was considered by using the amount of dogs in Helsinki and the results of the measurements, and reflecting them in the international scientific studies. The results were also compared with a survey ”Koirat kaupungissa” that was published by the city of Helsinki in 2017. The results of the measurements show that the dog population of Helsinki put out approximately 1 358 tons of manure per year, and 148 tons of that amount end up in the streets and the park environment despite of the sanitation law. Slight differences between parks were discovered: in relation the largest amount of excrements were left uncollected in the Runar Schildt park, in the suburban area in the northwest of the city of Helsinki. The dog excrement bag materials variated in the trash bins. The waste management could theoretically benefit of standardization of the bags, and it could be beneficial to get all the manure collected in bags that compost easily and would be composted. The nutrients of the excrements could be then collected and taken advantage of. This was anyhow found difficult, because even the best of the bag materials do not compost properly, and are being burned as mixed garbage with the dog excrements. The effects of dog excrements in the urban areas are also considered in this study.
  • Ortamala, Mikko (2018)
    Kokonaisvaltainen maatalousympäristön vesienhallinta pitää sisällään perus- ja paikallis-kuivatuksen sekä valumavesienhallinnan toimenpidekokonaisuuden huomioiden luonnon monimuotoisuuden ja kalatalouden tarpeet. Tämän tutkielman tavoitteena on ollut kirjallisuuden sekä käytännön toimijoiden raporttien avulla laatia toimintatapamalli maatalousympäristön tuotantotalouden kehittämiseen sekä vesistökuormituksen vähentämiseen. Kokonaisvaltaisella vesienhallinnalla tähdätään tulvien ja märkyysongelmien poistoon sekä maanrakenteen ja kasvukunnon parantamiseen ja tätä kautta kiintoaine- ja ravinnekuormituksen vähenemiseen. Kokonaisvaltainen toimintatapa tavoittelee yhdenaikaista tuottavuuden kasvua sekä vesien- ja luonnonhoidon turvaamista sekä tuotantotalouden ja ympäristönhoidon yhteensovittamista. Peruskuivatuksia koskevan kunnostustarpeen on todettu olevan huomattava ja vesienhallinnan rakenteiden korjausvelan olevan suuri. Maatalouden toimintaympäristössä tapahtuneiden muutosten myötä toimenpiteiden toteuttaminen on hankaloitunut ja monimutkaistunut. Toimenpiteiden järjestelmälliseen ja laajamittaiseen toteuttamiseen tarvitaan valuma-aluekohtainen toimintatapamalli. Valuma-aluekohtainen toimintatapamalli kokoaa yhteen ne toimenpiteet, joilla maatalous-alueiden tuotantotaloutta sekä vesien- ja ympäristönhoitoa voidaan valtakunnallisesti edistää ja toteuttaa yhdenaikaisesti. Tarvitaan laajamittainen riskialuekartoitus ongelma-alueiden selvittämiseksi ja tiedotuksen kohdentamiseksi. Ojitusyh-teisöt tulisi palauttaa ojitusisännöitsijöiden kanssa vastaamaan ojien huollon- ja kunnossapidon järjestämisestä yhdessä suunnittelijoiden kanssa. Vesienhallinta tulisi myös saada osaksi tilakohtaista viljelysuunnittelua. Valuma-aluekohtaisen toimintatapamallin mukainen järjestelmällinen toimintaketjun sisältävä vaiheittainen toteutus valuma-alueelta vesistöön takaa todennäköisesti laadukkaimman lopputuloksen kuivatustilan parantamiseksi ja vesistökuormituksen vähentämiseksi. Korjausvelan ollessa suuri tulisi pyrkiä pois toimenpiteiden epäsuunnitelmallisesta ja epäsystemaattisesta toteuttamisesta. Laajamittaisessa kansallisessa toteuttamisessa ei ole oikein toteutettuna kyse pelkästään vesienhallinnasta ja ympäristönhoidosta vaan myös maanarvon ja bruttokansantuotteen kasvamisesta sekä infrastruktuurin kunnossapidosta.
  • Larkiala, Jonna (2018)
    Obesity is a health problem linked to Western lifestyle and it is becoming more general. The complexity of regulation of eating makes it difficult to regulate body weight, when multiple neural networks and regions of brain have overlapping functions regarding to energy gain. Sufficient amount of energy is vital for individuals surviving in their living environment. Cholinergic messaging in brain is wide and for example nicotine is known for its appetite reducing effect. Anorexigenic proopiomelanocortin neurons mediate the effect of nicotine. In nucleus accumbens and central nucleus of amygdala extracellular levels of acetylcholine rise during meal, which promotes satiety. Satiety inhibits eating behavior between meals. Amygdala is a part of limbic system and in earlier knowledge it was associated only to regulation of memory, conditioning and fear. Nowadays importance of amygdala in eating behavior research is rising, but most of the studies focus on the effect of cue in regulation of eating. Cholinergic messaging is vigorous in the amygdala and is received from opposite areas of brain between basolateral and central amygdala and therefore this master’s thesis examined the effect of cholinergic messaging in amygdala on regulation of eating behavior. C57BL/6JRcc male mice were stereotaxically implanted with guide cannulas either in the basolateral complex of amygdala (n=10) or central nucleus (n=13). After recovering and habituation to automated pellet dispenser mice were treated with nicotinic and muscarinic receptor agonists and antagonists and eating behavior was recorded for six hours. Nicotine, administered to central and basolateral part of amygdala, lowered the number of pellets mice ate. In central nucleus effect was dose dependent. Mecamylamine had time related effect on eating behavior in basolateral amygdala, but dose dependent response was seen only in cumulative results. Oxotremorine was the only compound which created statistically significant interaction between time and dose. Result was seen in both groups. Scopolamine reduced eating behavior in central nucleus and dose dependency was seen. In basolateral complex scopolamine had time related effect, similar to mecamylamine. The results suggest that amygdala regulates eating behavior even without cue.
  • Söyrinki, Siiri (2019)
    Tiivistelmä – Referat – Abstract Variable electricity production poses challenges for the electricity grid, where demand and production must be balanced at all times. Transition to variable electricity production requires new solutions for grid flexibility. Electricity consumption has traditionally been an inflexible component in the electricity system but technological development enables demand side flexibility. Demand response (DR) is demand side measure, where energy consumption is shifted due to an external incentive. DR has multiple benefits such as improving reliability with high integration of variable energy production and cutting emissions during peak production. Despite years of modelling and analysing DR, there is lack of experience with commercial end-users in real-life context. In recent years, transmission system operator Fingrid has conducted experiments with stakeholders to find new demand response resources outside the traditional industrial end-users. The market models and services have not yet matured and therefore actors experiment to find solutions to resolve demand response barriers. The difficulty of scaling up sustainable innovations is a well-known challenge in energy transition research. In strategic niche management theory experiments are seen as tools for sustainable transition. This qualitative case study examines how piloting demand response in grocery store promotes energy transition. I chose the case of Virtual Service Environment (VIRPA-B) experiment, where participants tested DR in two grocery stores. The data were gathered in eight interviews with stakeholders and experts and through literature review. With theoretical framework I analysed, how the experiment contributes to implementation of demand response through expectations, learning and the ways pilot was scaled up after the experiment. Thesis sheds light to stakeholders’ role in implementing new technology and business model in real-life context. The results indicate that DR does not disturb the functions of the grocery store. The technology is matured, but the instalment practises have not been standardized. The greatest barrier for upscaling seems to be the regulations of the electricity markets, as they do not encourage end-users to invest in DR. VIRPA-B experiment did not lead to a rapid upscaling. However, lessons scaled up through other projects that support the niche development. For actors experiments are a platform to develop expertise and influence the new business models. To overcome the barriers, more attention should be directed at the synergies between the technologies. In VIRPA-B pilot actors noted benefits with solar panels, energy efficiency and DR. Combining technologies can lead to significant electricity savings. Promoting DR as a part of intelligent building automation system could also help overcome DR barriers. The results of thesis indicate that experiments can produce capabilities that promote energy transition.
  • Kraft, Hanna (2018)
    Liposomes are nanosized drug delivery vesicles composed of phospholipid membranes. They present an attractive drug delivery system due to their bioavailability and flexibility. Liposomes can be prepared by different techniques. They can carry both hydrophobic and hydrophilic molecules and their surface can be modified with targeting molecules. Coating the liposome surface with the PEG derivative makes their pharmacokinetics easier to predict. There are several liposome-based medicinal products already on the market. Triggering of drug delivery systems by different external or internal stimuli allows precise control of drug release. Light-triggered drug release is an attractive alternative due to the easy control and regulation of the stimulus. The problem with light-triggered therapy has previously been the need to use high-energy ultraviolet light that penetrates badly to the tissues and is not safe. In TTA-UC process the low-energy red or green light is converted to high-energy blue light. In this process photosensitive molecules are excited by visible light and after that the energy is transferred from sensitizer to annihilator molecules. Collision of two annihilators leads to the excitation of the other molecule while the other returns back to its general energy state. The excitation breaks up with fluorescence. In this process the highly permeable and safe red light is converted to blue light which has enough energy to induce drug release. The aim of this work was to optimize liposomal preparation method and prepare a pegylated and stabile liposome formulation for TTA-UC process. Hydrophobic light sensitive molecules were loaded into the phospholipid membrane as much as possible. One of the problems in this work was to find proper methods to measure the concentrations of these molecules. The lipid composition for formulation was chosen after thermostability studies. As a quality control, the size, capability to load calcein and phase transition temperature of liposomes were measured. The quality control of light sensitive molecules was operated too. In this work, the formulation for TTA-UC was prepared. In further studies TTA-UC process happened with sufficient efficacy. The formulation was pegylated and stable in physiological conditions and the concentrations of the molecules were high enough. This was the very first time to get TTA-UC to happen in this kind of liposome formulation that may be useful as a drug carrier. Long-term stability studies and further optimization of TTA-UC method are needed in the future. Some drug release studies are important to arrange in the future, too.
  • Itämö, Satu (2018)
    Marketing authorized pharmaceutical preparations that are aimed at adult use cause problems both in administration and when dosing. Over and underdosing are the most common medication errors in pediatric population. Only a fraction of medicinal products are clinically tested and evaluated for pediatric use. Children should have the right for the best achievable health, medical care and rehabilitation. The aim of this study was to determine problematic pharmaceutical preparations, formulations or excipients experienced by healthcare professionals. The another aim of this study was to comprise (?) the view of healthcare professionals about 3D-printed medicinal products by using the collected data. By using the data, the problems, challenges, targets for development and other suggestions regarding pediatric medication were identified. New 3D printed medicines suitable for children can be developed by using the observations of this study. The study was carried out as semi-structured interview. Frameworks of the themes were structured by using the subjects of a recently made semi-structured questionnaire. The semi-structured interview was carried out as a group-interview, where the participants were presented open questions according to the themes structured before. According to the study results, the prejudices of the interviewees towards the new technology were mainly positive. The adjustability of the printed medicine by the means of the patient was most highlighted property in the interviews. Accoring to the experiences of the interviewees’, the most suitable pharmaceutical preparations used are liquid preparations such as oral liquids or suspensions. When using solid oral formulations, the age of the patient was not seen as significant. The most common reason for compounding the preparation was the wrong size of the product or dose. The varying availability of pharmaceutical preparations was seen as delaying factor at the start of the medical treatment. In the interview the pharmacists recognized the most common excipients causing adverse events. The different roles of the occupational groups were identified according to their work duties.
  • Sund, Nina (2018)
    Laxpopulationer både globalt och i Finland är hotade som följd av överfiske och förstörda livsmiljöer. För att bevara och återuppliva naturliga laxpopulationer har man länge planterat ut laxar odlade i fiskodlingsanstalter. Dock är det endast en liten andel av de utplanterade laxarna som överlever till fortplantningsålder vilket gör utplanteringen både ekonomiskt och etiskt ohållbar. Orsaken till att så få av de utplanterade fiskarna överlever i naturen anses vara att de är dåligt anpassade till de naturliga förhållandena, eftersom miljöförhållandena i odlingsbassänger och naturen skiljer sig starkt från varandra. Målet med denna studie var att ta reda på ifall berikade odlingsbassänger med mer varierande och naturenliga förhållanden, vore ett alternativ att förbättra de utplanterade fiskarnas duglighet genom bättre anpassade morfologiska egenskaper. Jag undersökte morfologiska skillnader mellan laxar med olika härstamning; fiskar med vilt ursprung och odlat ursprung, vilka härstammade från fiskar som levt i naturen ända fram till fortplantningsålder och fiskar som under flera generationer levt i odlingsförhållanden. Fiskarna växte upp i olika miljöer, vanliga bara odlingsbassänger och berikade bassänger, och släpptes därefter ut i konstgjorda strömmar för att efterlikna en utplantering. Jag förväntade mig att fiskar som växt upp i berikade bassänger skulle ha lättare att anpassa sig till sin miljö, eftersom en varierande uppväxtmiljö anses bidra till fiskens förmåga att anpassa sig till miljöförändringar, och även att fiskarna med vilt ursprung skulle anpassa sig bättre, eftersom odlade fiskar anses mista genetisk diversitet till följd av bl.a. domesticering. Jag undersökte ifall det fanns morfologiska skillnader mellan fiskarna före de släpptes ut i de konstgjorda strömmarna då de växt upp i olika miljöer, och efter att de levt i samma miljöförhållanden i de konstgjorda strömmarna samt hurdana skillnader som uppkommit, genom att analysera fotografier. Fiskar med odlat ursprung uppvisade större morfologisk variation mellan de olika uppväxtförhållandena än fiskarna med vilt ursprung innan utplanteringen, medan fiskar med vilt ursprung uppvisade större morfologiska skillnader efter att de levt i de konstgjorda strömmarna. Både före och efter den efterliknade utplanteringen hade fiskar som växt upp i berikade bassänger en högre kropp. Fiskar med odlat ursprung hade både högre huvud och bakkropp än fiskarna med vilt ursprung efter utplanteringen, vilket indikerar en jämntjock kroppsform. Jag undersökte även fiskarnas specifika vikttillväxthastighet. Fiskarna från berikade uppväxtförhållanden, speciellt de med vilt ursprung, ökade i vikt, medan fiskar med vilt ursprung som växt upp i standard förhållanden minskade i vikt under den tid de levde i de konstgjorda strömmarna. Fiskarnas morfologiska variation påverkades mest av uppväxtförhållandena. Fiskar som växt upp i berikade bassänger hade störst tillväxt vilket tyder på att de kunde anpassa sig bättre till förhållandena i de konstgjorda strömmarna och var bättre på att hitta föda än fiskar från standard bassänger. Fiskar som växt upp i berikade bassänger hade även högre kropp, vilket indikerar att de anpassat sig till strömmande vatten. Även fiskarnas ursprung påverkade deras morfologiska egenskaper. Fiskar med vilt ursprung var mer spolformade och strömlinjeformade, vilket anses vara fördelaktigt vid simning, än fiskar med odlat ursprung som hade en mer jämntjock kroppsform. De morfologiska skillnaderna mellan fiskar med olika ursprung, kunde tyda på skillnader i fiskarnas fenotypiska plasticitet, d.v.s. förmågan hos en genotyp att anpassa sin fenotyp som gensvar på miljön. Resultaten tyder på att berikade uppväxtbassänger påverkar laxarnas morfologiska egenskaper så att de lättare kan anpassa sig till ett liv i naturen, och kunde således vara ett alternativ för att producera mer dugliga fiskar för utplantering i framtiden
  • Bruun, Tanja (2018)
    Marine organisms can be regarded as a diverse source of bioactive compounds with the possibility to discover novel drug lead molecules. Sea sponges produce bromine containing alkaloids, bromotyrosines, from which several are active against cancer. Some bromotyrosines have spirocyclic structure and the innate three-dimensionality and structural novelty of spirocycles make them an interesting option in drug design. Clavatadine C, extracted from sponge Suberea clavata, is a bromine containing spirocyclohexa-dienylisoxazoline alkaloid. It’s symmetric spirocyclic core can be viewed as a restricted derivative of open chain oximes, such as purpurealidin I, a bromotyrosine extracted from Pseudoceratina purpurea. Earlier work with purpurealidin I derivatives against melanoma cell line has had some promising results. Inspired by these earlier results, eight spirocyclic clavatadine C derivatives were synthesized according the published synthesis route. The activities of seven synthesized clavatadine C derivatives were tested on A375 melanoma cell line. All spiro derivatives were active with CC50 values ranging between 1.0 μM and 3.4 μM. Also, the activities of 10 earlier synthesized bromotyrosine derivatives were tested, from which four open chain oximes had CC50 values between 13.5 μM and 27.8 μM. Interestingly, the most active compounds were chlorinated and unhalogenated spirocyclic derivatives. In general, the spirocyclic compounds were 2- to 8-fold more active than the corresponding open chain oximes. The selectivity of active compounds was determined as cytotoxicity against Hs27 fibroblasts and by comparing the CC50 values of these two cell lines. The most selective compound was brominated derivative which had three times better selectivity against melanoma cells. The weak selectivity was consistent with the trend with open chain oxime analogs. Despite the selectivity issue, the improved activity of spirocyclic derivatives are promising and support for further investigation of marine-based spirocyclic bromotyrosine derivatives against melanoma.
  • Tiilikainen, Joni (2018)
    nxiety disorders are the most common psychiatric disorders. Iiris Hovatta’s group (Neurogenomics lab) uses inbred mice to study effects of psychosocial stress. Mice can be divided to susceptible and resilient phenotypes, based on their behavioral response to psychosocial stress. Differences between phenotypes can be examined for example on brain structural or transcriptional levels. These studies have shown changes in brain myelination and expression levels of myelin-related genes between phenotypes. Transcriptomic studies have also revealed differences in microRNA (miRNA) expression profiles. Especially miR-219a, a known regulator of myelination, appears to be differentially expressed. Bioinformatic studies also revealed that many predicted target genes of miR-219a are connected to Wnt/β-catenin signaling pathway, which is also known to regulate myelination. This led to a hypothesis that miR-219a regulates myelination through Wnt/β-catenin signaling pathway in adult mouse brain. Prediction of miRNA target genes is based on algorithms using varying criteria, and their biological significance is uncertain. Assumptions about the biological role of specific miRNA require experimental validation of the silencing interaction between the miRNA and the target gene mRNA. The purpose of this study was to validate five Wnt-signaling related mouse genes (Gsk3b, Esr1, Tcf7l2, Fkbp5 and Acvr1b) as targets for miR-219a-5p or miR-219a-1-3p. For validation a luciferase-reporter assay was used, in which the target sequence of the gene’s mRNA is cloned to a reporter vector, then cotransfected to cultured cells (human HEK293 cells) with a miRNA-mimic. The light emitting luciferase activity is measured to examine the possible silencing effect of the miRNA. Results of this study showed that miR-219a mimics did silence the expression of the target genes. Although some variation was observed in the efficiency of silencing between the genes and based on the mimic concentration. The most efficient silencing was observed between miR-219a-5p and Gsk3b construct. These results implicate that miR-219a regulates several genes related to Wnt/β-catenin pathway, and that stress-related differences in its expression may be associated to differential myelination observed between phenotypes that react differentially to psychosocial stress.
  • Molari, Joonas (2018)
    Currently, there is an undeniable need for more effective treatments of depression. The efficacy of traditional antidepressant drugs becomes apparent after multiple weeks of treatment. New advancements in depression treatments have been made, as glutamatergic NMDA-receptor antagonist ketamine is seen to ameliorate symptoms rapidly, even only hours after drug administration. Understanding ketamine’s mechanism of action as an antidepressant could enable the development of more effective antidepressant drugs. The critical molecular level component in ketamine’s antidepressant effect is considered to be the activation of TrkB tyrosine receptor kinase B, which subsequently leads to the initiation of signaling pathways, which regulate synaptic plasticity. So far, it has not been examined; whether there is a difference in ketamine’s antidepressant effect based on the dosing-time of day. The aim of the present study was to find out if there is a variation between ketamine’s effect on synaptic plasticity and the circadian phase in which the drug is administered. Ketamine’s (200 or 50 mg/kg, i.p.) effects were studied in C57BL/6J–mice during light phase (mouse’s inactive phase) and dark phase (mouse’s active phase) of the day. The phase of the day didn’t affect the activity of TrkB signaling in its related parts (pTrkBTyr816, pGSK3βSer9, p-p70S6KTyr421/Ser424 and p-p44/42MAPKThr202/Tyr204) in prefrontal cortex samples which were analysed in Western blot assay. Ketamine increased dose-dependently the phosphorylation of GSK3βSer9 and p70S6KTyr421/Ser424 as well as decreased p-p44/42MAPKThr202/Tyr204 at 30 minutes after drug administration in both phases of the day. Ketamine (200 mg/kg, i.p.) also lowered the glucose concentration measured from the trunk blood. To examine the effect of hypoglycemia on the activity of TrkB signaling another experiment was conducted. The hypoglycemia induced by insulin detemir (6 IU/kg, i.p.) didn’t affect any measured protein phosphorylation at 60 minutes after drug administration. The results of this study support the notion of ketamine’s rapid and dosedependent induction of neuroplasticity. The possible role of hypoglycemia in ketamine's neuropharmacology should be investigated in future studies.
  • Kari, Otto K. (2018)
    Nanolääkkeiden pinnalle elimistössä muodostuva biomolekyylikerros eli proteiinikorona vaikuttaa muun muassa jakautumiseen, toksisuuteen ja soluvuorovaikutuksiin. Koronan ominaisuuksien tuntemus jakautumisen eri vaiheissa on siten edellytys tehokkaampien ja turvallisempien nanolääkkeiden kehittämiselle, mutta kehitystyötä on hidastanut soveltuvien menetelmien puute. Turvallisuuden ja tehon ennakoinnin osalta on korostettu leimavapaiden in vitro -menetelmien tarvetta. Tutkielmassa kehitettiin multiparametriseen pintaplasmoniresonanssilaitteistoon ja laskennalliseen mallinnukseen perustuva menetelmä liposomien koronan tiheyden ja paksuuden määrittämiseen. Toisin kuin koronan tutkimiseen yleisesti käytetyt menetelmät, valoon perustuva kajoamaton ja leimavapaa menetelmä ei vaikuta koronan rakenteeseen. Näin voidaan tutkia myös löyhemmin sitoutuneista proteiineista muodostunutta pintakerrosta, mikä vastaa keskeisimpään kirjallisuuskatsauksessa todettuun menetelmäpuutteeseen. Menetelmää sovellettiin neljän biosensorille immobilisoidun liposomiformulaation pinnalle ihmisen seerumissa muodostuvan koronan tutkimiseen. Sen avulla oli mahdollista määrittää ensimmäistä kertaa tiiviin ja löyhän koronan tiheys ja paksuus laimentamattomassa seerumissa. Tulokset tukevat käsitystä ns. erotteluhypoteesin kuvaamasta erillisestä löyhästä proteiinikerroksesta ja avaavat uusia mahdollisuuksia sen biologisen merkityksen arviointiin. Lisäksi voitiin määrittää ensi kerran opsoniinimolekyylien sitoutumiskinetiikka liposomien pinnalle, minkä avulla voidaan arvioida nanolääkkeiden taipumusta poistua verenkierrosta ja aktivoida sisäsyntyinen immuunipuolustus. Menetelmä soveltuu siten liposomien koostumuksen ja pinta-arkkitehtuurin optimointiin prekliinisessä lääkekehitysvaiheessa.
  • Mercier, Léon (2018)
    PURPOSE AND GOALS Microalgae are unicellular eukaryotic organisms capable of photosynthesis. They harvest sunlight and efficiently take up carbon dioxide and nutrients such as nitrogen and phosphorus from their environment and use them for their growth. Due to these properties, their rapid growth and ability to survive in a variety of environments, microalgae have potential in biotechnological applications that promote nutrient recovery and recycling, water purification and the carbon neutral production of biochemicals and possibly biofuels. The purpose of this study was to investigate the suitability of a side stream water originating from the production of baker’s yeast (yeastwater) for the cultivation of a species of microalga called Euglena gracilis. The study aimed to determine the capacity of this water to support growth and protein production of E. gracilis as well as the capacity of E. gracilis to remove nutrients from the water. The effect of filtration of the water on these parameters was also studied. Yeastwater contains an organic molecule called betaine in relatively high concentrations. Betaine has previously been shown to boost the production of the important vitamin cobalamin in bacteria. The study aimed to determine the effect of betaine on the growth of E. gracilis and on the production of cobalamin in the algal-bacterial symbiosis. METHODS E. gracilis was cultured in laboratory scale photobioreactors. Its growth, protein production and nutrient uptake capacity was determined. Baker’s yeast production side stream water diluted with MQ-water was used as the growth medium either in filtered or unfiltered form. A control treatment was prepared where no microalgal inoculate was added to the photobioreactor. The same microalga was also grown in a synthetic nutrient medium with and without betaine. The uptake of betaine and biomass concentrations of cobalamin were determined. For the determination of microalgal growth, dry weight determination and flow cytometry analysis were used. Protein production was determined on the basis of total nitrogen concentration in the biomass. Spectrophotometric measuring kits were used for the determination of nutrient concentrations. Liquid chromatography techniques were used for the determination of betaine and cobalamin concentrations. RESULTS Significant microalgal growth was observed in filtered yeastwater, while growth in unfiltered yeastwater was very low. Nitrogen removal was higher in presence of E. gracilis compared to the control treatment. Protein production in yeastwater was comparable to that of microalgae grown in synthetic medium. E. gracilis grew much better in the synthetic media supplemented with betaine than without the addition. Betaine enrichment had no effect on cobalamin production. Cobalamin was produced in unfiltered yeastwater both with and without the presence of E. gracilis. CONCLUSIONS Unfiltered yeastwater does not support growth of E. gracilis possibly due to its high turbidity. Filtered yeastwater, on the other hand can support the production of E. gracilis biomass. E. gracilis can be used to reduce nitrogen concentrations in yeastwater. Yeastwater can support cobalamin production by bacteria, but this phenomenon did not benefit from the presence of the microalga. The effect of betaine on microalgal growth warrants further study to determine whether it is related to the accumulation of intracellular nutrients, storage compounds or to some other phenomenon. Yeastwater is a promising nutrient feedstock for microalgal biomass production. However, the role of filtration and possibility of using other methods for turbidity reduction needs to be further studied.
  • Kauppinen, Vera (2018)
    2000-luvun alussa tapahtuneiden suurten tulvien jälkeen Euroopan Unionissa on tapahtunut paradigmanmuutos, jossa teknisiin ratkaisuihin keskittyvästä tulvasuojelusta on siirrytty kohti kokonaisvaltaisempaa tulvariskien hallintaa. Myös Suomessa on ollut suuria tulvia 2000-luvulla ja tulvariskien arvioinnin ja hallinnan direktiivin puitteissa on nimetty 21 merkittävää tulvariskialuetta. Samaan aikaan resilienssi on omaksuttu katastrofiriskien hallinnan yhdeksi tavoitteeksi. Resilienssi on systeemin kykyä vastata muutokseen tai häiriöön. Tämän pro gradu-tutkielman tarkoituksena on selvittää yhteisön resilienssin kehittymistä sekä keskeisiä resursseja ja toimijoita Kittilän tulvariskien hallinnassa. Tutkimuksen viitekehyksenä toimii yhteisön resilienssi, joka tarjoaa mahdollisuuden kiinnittää tarkempaa huomiota luonnonkatastrofien ja niiden hallinnan sosiaaliseen ulottuvuuteen. Tässä tutkimuksessa yhteisön resilienssi on määritelty yhteisön selvitymis-, sopeutumis- ja transformaatiokykynä häiriöiden kontekstissa. Tutkimuksen analyyttinen viitekehys jakaa yhteisön resilienssin kolmeen osa-alueeseen, jotka ovat resurssit ja kyvyt, toiminta sekä oppiminen. Osa-alueet ovat vuorovaikutuksessa toisiinsa ja niihin vaikuttavat myös yhteisön ulkopuoliset rakenteet, kuten katastrofiriskien hallinta sekä sosio-poliittinen, taloudellinen ja ympäristöllinen konteksti sekä niiden muutokset ja häiriöt. Vastauksia tutkimuksen kysymyksiin selvitettiin tapaustutkimuksen avulla. Tutkimuksen tapauksena on Kittilän vuoden 2005 tulva. Tutkimuksen aineistona ovat paikallisten ja alueellisten toimijoiden teemahaastattelut sekä tulvariskien hallintaa koskevat asiakirjat. Aineisto analysoitiin laadullisen sisällönanalyysin avulla käyttäen apuna Atlas.ti-analyysiohjelmaa. Yhteisö tulvariskien hallinnassa käsittää sekä institutionaaliset, järjestäytyneet että epäviralliset toimijat. Tulvariskien hallinta Suomessa on vahvasti institutionalisoitu ja vastuu viranomaisilla, mutta Kittilän tapauksessa asukkaiden ja heidän sosiaalisten verkostojensa toiminta oli tärkeässä osassa tulvasta selviytymisessä. Yhteisön resilienssin kannalta merkittävin resursseista oli yhteisön sosiaalinen pääoma, sillä sen avulla yhteisö pääsi käsiksi myös muihin resursseihin. Toimijoiden sosiaaliset verkostot olivat linkittyneet toisiinsa ja ulottuivat useammalle maantieteelliselle tasolle. Tulvan jälkeen toiminta oli kehittynyt järjestelmällisemmäksi ja ennakoivaksi. Vuoden 2005 tulvan jälkeen erityisesti varautuminen tulviin, instituutionaalisten toimijoiden organisaatiorakenteet ja yhteistyö, materiaaliset resurssit, tekniset ratkaisut sekä riskitietoisuus kehittyivät parempaan suuntaan. Vuoden 2005 tulvan jälkeen tapahtui pääasiassa yksikehäistä oppimista, jossa toimintaa muutettiin tulvakokemuksen perusteella. Kaksikehäistä oppimista ja kriittistä tarkastelua oli myös jonkun verran, mutta monikehäinen oppiminen ja yhteisön resilienssin transformatiivinen ulottuvuus puuttuivat kokonaan. Tulvariskien hallinta perustui vuoden 2005 tulvan jälkeen kunnan hallinnossa hyväksytyille tulvapenkereiden rakentamiselle, jotka olivat viivästyneet huomattavasti ja edelleen rakentamatta. Yhteisön resilienssiä tulville tulisi pystyä kehittämään, myös sellaisilla riskialttiilla alueilla, joilla ei ole viimeaikaisia tulvakokemuksia. Samalla yhteisöjen tulisi olla resilienttejä kaikenlaisille muutoksille, myös vaikeammin havaittaville ja hitaille sosio-ekologisille muutoksille, kuten ilmastonmuutokselle tai huoltosuhteen heikkenemiselle. Yksi ratkaisu voisi olla transformaatio, joka mahdollistaa ulkoisista häiriöistä selviytymisen lisäksi sosiaalisen systeemin siirtymisen kohti ekologisesti kestävämpää ja sosiaalisesti oikeudenmukaista tilaa. On myös muistettava, että yhteisön resilienssi on sidoksissa kontekstiin eli siihen vaikuttaviin ulkopuolisiin prosesseihin ja rakenteisiin. Tiedon yhteistuotannon ja tutkimushankkeiden yhteissuunnittelun avulla voitaisiin saada tietoa yhteisön resilienssistä, joka on sosiaalisesti kestävää, paikalliseen kontekstiin sopivaa ja jota voidaan suoraan hyödyntää yhteisön toiminnassa. Osallistavat tutkimusprosessit voivat myös vähentää konflikteja esimerkiksi tulvariskien hallinnan keinoista sekä lisätä riskitietoisuutta niillä alueilla, joilla ei ole aiempia katastrofi- tai häiriökokemuksia. Tutkimuksen aikana tuli esille myös jatkotutkimustarpeita. Yhteisön resilienssiä tulisi edelleen tutkia laajemmin sekä Kittilässä että muilla tulvariskialueilla esimerkiksi määrällisten tutkimusmenetelmien avulla tai suuremmalla aineistolla. Sosiaalisia resursseja on korostettu yhteisön resilienssille luonnonkatastrofeissa ja tässäkin tutkimuksessa ne tulivat monin tavoin esille. Tämän takia olisi mielenkiintoista tutkia myös sosiaalisten resurssien kehittymistä ja tarkempaa suhdetta luonnonkatastrofeihin. Esimerkiksi pitkittäistutkimukset riskialueilla voisivat tuoda lisää tietoa sosiaalisista resursseista ennen ja jälkeen luonnonkatastrofin
  • Sandholm, Laura (2018)
    Peatlands are globally important ecosystems as they have been estimated contain about 40 % of the global soil carbon pool. Therefore, in light of the projected increase in temperatures and possible increase in fire frequencies, it is of great importance to understand how peatlands are expected to develop under changing climate conditions. Currently it is estimated that of western continental Canadas 365 000 km2 peatlands, around 28 % are underlain by permafrost which however store about 38 % of the soil carbon in the area. Climate change is expected to affect these peatlands very quickly, because they are situated at the dry limit of peatland distribution. Peatlands develop in areas where production of new organic material exceeds the decomposition rate, whereby dead plant material will start to accumulate as peat, and thus, atmospheric carbon that has been seized in the plant material will become stored. Peat is stored in the peatland in the order that it accumulates, with the oldest material at the bottom end newest at the top, thereby making it possible to infer the succession of the stored vegetation. Permafrost may aggregate in peatlands due to cold climates and the insulating effect of peat moss. Fires usually cause severe combustion of peat plateaus, because they exhibit a dry and aerated surface and high tree vegetation cover. As fires remove peat through combustion, permafrost may collapse. As the permafrost within the peat plateau collapses it causes the peatland surface to subside, producing collapse areas which exhibit different hydrological conditions from the surrounding plateau. Due to a lack in knowledge about how peat plateaus have developed and reacted under different fire regimes, throughout their developmental history, it is difficult to say how they will react to future changes. Also very little is known about the actual mechanism behind initial peat plateau development or about what factors are important in determining whether permafrost will re-aggregate after collapse. With my thesis I will add to the knowledge about the initiation and developmental history of permafrost containing peatlands within the zone of discontinuous permafrost in continental northwestern Canada. I investigate the initiation patterns and effects of fires on peatland development by examining peat cores from three different peatlands in British Columbia, Canada. Each core is analysed for changes in peat main components and plant species composition throughout the peatland developmental history. As different species have different ecological range for example in regards to moisture and nutrient conditions, one can infer these based on the plant species community. In order to see when the peatlands initiated the bottom of the organic material was dated through radiocarbon dating. All peatlands initiated through onto ground formerly occupied by upland forest vegetation, which however also caused the dated samples from the bottom of the cores not to be very informative in regards to the actual peatland initiation time. The northernmost site, with the thickest peat, shows clear signs of being a permafrost affected peatland, starting from the initial peat accumulation to present day. The two other sites are more diverse in their development as they show signs of both permafrost peatlands and of sites that have undergone permafrost collapse. The peat on the permafrost affected peatlands has accumulated very slowly. Current peat accumulation rates, counted based on tree ring data and correlated to charred layers in the peat, show that the peatland areas that have collapsed, actually accumulate peat more quickly than the peat plateau with permafrost. This may indicate that as long as peatlands are still able to endure under warmer climates, it may be that they will actually accumulate more carbon due to higher production under non-permafrost conditions.
  • Luoma, Maaria (2018)
    Inappropriate polypharmacy refers to a situation where more than appropriate amount of medicines are used by a patient. Aged people with multiple morbidities and medications use a lot of health care services and are thus especially vulnerable to iatrogenesis, the health hazards resulting from the acts of a health care system. As a part of normal ageing, geriatric syndromes (e.g. falls, delirium and urinary incontinence) are clinical conditions and symptoms crossing several organ systems and they cannot be connected to a certain individual disease. Geriatric syndromes complicate recognition of adverse drug reactions on aged. This increases the risk of prescribing cascade, where medicines are prescribed to treat adverse drug reactions caused by another medicine. In this master´s thesis the root causes for inappropriate polypharmacy and drug-related problems (DRP) with home-dwelling aged were researched retrospectively from the viewpoint of risk management. Research method was based on root cause analysis (RCA) that was simplified suitable for this research. Research material was based on an intervention research conducted in 2015– 2017 on home-dwelling aged receiving regular home care from the City of Lohja, Finland. In the intervention research, a coordinated community-based medication management model for home-dwelling aged in primary care was developed to identify homedwelling aged with clinically significant drug-related problems. As research material, there were five (n=5) patient cases used who received comprehensive medication review (CMR) in the intervention research to solve their drug-related problems. The research material composed of individual patient interviews conducted at patients’ homes as a part of their CMR visits. Also, the nurses (n=3) of home care and physicians (n=2) from local health centres having participated in the treatment of the home-dwelling aged in question, were interviewed individually. Markings made in the patient records were utilized as well as research material. The interviews of the nurses and physicians were recorded, transcribed and analysed with inductive content analysis considering principles of root cause analysis. According to the nurses and physicians, central clinically significant medication-related problems with home-dwelling aged are various prescribing care parties, multiple medications, the increased use of over-the-counter (OTC) medicines and natural products, the uncertainty of health care professionals of the medication of a home-dwelling aged as well as the occurrence and medication of pain and sleeping disorders with aged. Other essential problems related to the health care system are various attending physicians, obscurely recorded medication data in patient record system, the use of benzodiazepines and other psychopharmaceuticals and ignored renal function in medicine dose adjustment. Problems related to home-dwelling aged are attachment for medicines, resistance to change and desire to take care of their own medication. In addition, memory disorders and vertigo were mentioned as problems related to the medication of aged. Seven root causes for inappropriate polypharmacy and drug-related problems were observed: lack of health care resources, segmented treatment between various health care parties, varying skills and knowledge of health care professionals, ambiguous division of responsibilities between health care professionals, challenges in communication between different care parties, the heterogeneity of patient record systems and problems related to their use as well as the knowledge, opinions and personal situation of a home-dwelling aged. Based on the research, the medication of home-dwelling aged should be improved by striving for centralizing care in one physician either on private or public health care. Among home care nursing personnel there is a need for additional training on medications and pharmacists should participate in regular medication reviews for home-dwelling aged. Patient record systems and data transmission between them should be improved and medication data should be recorded more precisely. Cooperation and communication between home care and health centre should be developed and the division of responsibilities should be clarified. Participation of the home-dwelling aged and their relatives in the care should be promoted. Furthermore, geriatric expertise should be utilized better in the care of the home-dwelling aged.
  • Tseloev, Idris (2018)
    An ultra-high-pressure liquid chromatography method was used for simultaneous detection of 25 small peptide hormones and their metabolites in urine after solid-phase extraction. This method is first screening step in anti-doping analysis of urine samples. It should be fast, generic and able to detect any sample that may contain a prohibited substance while avoiding false negatives and reducing false positive results. Detection was achieved using quadrupole time-of-flight mass spectrometry coupled with electrospray ionization source in positive mode. Analytes included growth hormone secretagogues, gonadotropin releasing factors, anti-diuretic hormones and their metabolites which are all covered by the list of prohibited substances of the World Anti-Doping Agency (WADA). The practical part of investigation was done in United Medix Laboratories and the aim of study was to expand current screening method by adding new compounds. Optimal experimental conditions were stablished after investigation of different parameters concerning sample preparation and instrumental analysis. The extraction procedure was done by using weak cation exchange SPE with two washing steps (Milli-Q water and methanol), and elution with 5 % formic acid in methanol. The procedure was validated in terms of recovery, specificity, limits of detection, stability and robustness. Recovery was evaluated with 10 ng/ml concentration of analytes and the rest of validation procedures were done at half of minimum required performance level set by WADA (1 ng/ml). Recoveries ranged from 2,6 to 85 % with LODs from 0,01 to 1,76 ng/ml. The suitability of the method was assessed by analyzing different spiked urine specimens containing target substances.
  • Pikkarainen, Kaisa (2018)
    One open question related to microplastics found in seas is the sources and routes of microplastics into seas. In Helsinki about one third of the snow collected from urban areas is dumped directly into the Baltic sea. When snow is collected from an urban area also the possible waste in the snow becomes collected. This is the first study that examines the numerical quantity and the characteristics of waste in urban snow. In order to study waste contained in snow, samples were collected from three different urban areas in Helsinki in February 2016. Snow was collected from Hakaniemen tori, Kullervonkatu in Käpylä and Sörnäisten rantatie. Solid matter in snow samples was divided into particles sized over 4 mm and 0.3–4 mm. Waste particles were visually identified utilizing the morphology of the particles. Material of selected waste particles was analysed using a FTIR spectrometer. Snow samples collected from Käpylä contained more waste by weight and number than samples collected from other areas. Reasons for differences between sampling areas did not become clear in this study. The most common waste in urban snow were particles disengaged from asphalt pavement and road markings, along with paper, plastic and rubber waste. All snow samples contained microplastics. Urban snow contained more microplastics than purified wastewater leaving from Viikinmäki wastewater treatment plant and seawater in the Gulf of Finland. Stormwaters have been identified as a route for microplastics from urban areas into inland waters and seas, and according to this study also dumping of urban snow into seas acts as a route for microplastics. In urban snow road marking and plastic particles were the most common microplastics. In snow samples collected from road areas road marking particles were clearly the most common microplastic by number. In snow collected from Hakaniemen tori about half of the microplastics were plastic particles and almost a half road marking particles. Most of the microplastics in snow were different kinds of fragments. Like in earlier microplastics studies also in urban snow the most common materials of small plastic particles were polyethylene and polypropylene. In this study sources of the waste in snow are estimated to be the abrasion of asphalt pavement, road markings, tyres, plastic products and possibly also wood and metal products and different kinds of textiles. In addition to that numerous waste items had ended up in urban areas through littering or inadequate waste disposal. Littering is the most significant environmental impact of dumping urban snow into the sea in Helsinki. Marine Strategy Framework Directive states that properties and quantities of marine litter are not to cause harm to the coastal and marine environment. According to the guidelines of the City of Helsinki, snow that is brought to snow collection sites needs to be clean and not to contain waste. Nevertheless, according to this study through dumping snow into the sea in Hernesaaren ranta several thousand kilograms of waste and approximately over fifty million microplastic particles end up in the Baltic Sea. A monitoring program should be established to investigate and monitor the amount and the characteristics of waste in urban snow in Helsinki.