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  • Ruuska, Helka (1954)
  • Puranen, Anni (2011)
    Lipeä on vahva emäs, jonka on havaittu lisäävän hemiselluloosan ja ligniinin hydrolyysiä pötsissä. Näin ollen lipeäkäsittelyllä on mahdollista korvata viljan mekaaninen litistys ja jauhatus. Seosrehuruokinnalla, jonka osana on lipeäkäsitelty vilja, on mahdollista vähentää liiallisesta tärkkelyksestä aiheutuvia metabolisia ongelmia pötsissä. Tämän tutkielman tarkoituksena oli selvittää lipeäkäsitellyn vehnän vaikutusta lypsylehmien syöntiin ja tuotokseen ad libitum seosrehuruokinnoilla. Ruokinnoissa korvattiin kuivaa murskattua vehnää asteittain kokonaisella lipeäkäsitellyllä vehnällä. Kontrollina oli perinteisesti käytetty kuiva, murskattu ohra-kaura seos. Koe tehtiin Ruotsin maatalousyliopiston (SLU) maataloustieteiden laitoksella Uumajassa. Koe alkoi syyskuussa ja päättyi joulukuussa 2010. Kokeessa oli 17 useamman kerran poikinutta lehmää ja 6 ensikkoa (Ruotsin punainen -rotu). Lehmät olivat lämpimässä pihattonavetassa, jossa seosrehun syöntiä mitattiin vaakakuppien avulla. Koekäsittelyt olivat murskattu ohra-kaura seos (1:1), murskattu kuiva vehnä (1:0), murskatun kuivan vehnän ja kokonaisen lipeävehnän seos (1:1) ja kokonainen lipeävehnä (1:0). Ruokintojen kuiva-ainepitoisuudeksi asetettiin 370 g/kg ja raakavalkuaispitoisuudeksi 180 g/kg kuiva-ainetta. Näennäinen ravintoaineen sulavuus määritettiin happoon liukenemattoman tuhkan avulla. Typen hyväksikäyttöä arvioitiin laskennallisen typpitaseen avulla. Koe toteutettiin 4x4 latinalaisen neliön koemallin mukaisesti ja käsittelyjen väliset tilastolliset erot testattiin kontrastien avulla. Kuiva-aineen (PQ=0,02) ja orgaanisen aineen (PQ=0,02) syönnit lisääntyivät, samalla kun niiden sulavuudet paranivat korvattaessa puolet kuivasta vehnästä lipeävehnällä. Ruokintojen välillä ei ollut tilastollisesti merkitsevää eroa maitotuotoksessa eikä energiakorjatussa maitotuotoksessa. Maidon rasvatuotos lisääntyi vähän (PQ=0,04) ja rasvapitoisuus selvästi (PQ=0,004), kun kuivasta vehnästä korvattiin puolet lipeävehnällä. Kun kaikki kuiva vehnä korvattiin lipeävehnällä, maidon valkuaispitoisuus väheni (PL<0,001). Samoin kävi maidon ureapitoisuudelle (PL=0,002). Lipeäkäsittely ei tuottanut tässä kokeessa taloudellisesti kannattavaa tulosta, sillä maidon valkuaispitoisuus väheni ja syönti lisääntyi maitotuotoksen pysyessä samana. Vehnäruokinnoista paras tuotosvaste saatiin kuivan vehnän ja lipeävehnän seoksella.
  • Nurminen, Tuula (2006)
    The purpose of this thesis project is to study changes in the physical state of cell membranes during cell entry, including how these changes are connected to the presence of ceramide. The role of enzymatical manipulation of lipids in bacterial internalization is also studied. A novel technique, where a single giant vesicle is chosen under the microscope and an enzyme coupled-particle attached to the micromanipulator pipette towards the vesicle, is used. Thus, the enzymatic reaction on the membrane of the giant vesicle can be followed in real-time. The first aim of this study is to develop a system where the localized sphingomyelinase membrane interaction could be observed on the surface of the giant vesicle and the effects could be monitored with microscopy. Domain formation, which resembles acid sphingomyelinase (ASMase), causes CD95 clustering in the cell membrane due to ceramide production (Grassmé et al., 2001a; Grassmé et al., 2001b) and the formation of small vesicles inside the manipulated giant vesicle is observed. Sphingomyelinase activation has also been found to be an important factor in the bacterial and viral invasion process in nonphagocytic cells (Grassmé et al., 1997; Jan et al., 2000). Accordingly, sphingomyelinase reactions in the cell membrane might also give insight into bacterial or viral cellular entry events. We found sphingomyelinase activity in Chlamydia pneumonia elementarybodies (EBs). Interestingly, the bacterium enters host cells by endocytosis but the internalization mechanism of Chlamydia is unknown. The hypothesis is that sphingomyelin is needed for host cell entry in the infection of C. pneumonia. The second project focuses on this subject. The goal of the third project is to study a role of phosphatidylserine as a target for a membrane binding protein. Phosphatidylserine is chosen because of its importance in fusion processes. This will be another example for the importance of lipids in cell targeting, internalization, and externalization.
  • Jaatinen, Silja (Silja Jaatinen, 2009)
    In this thesis three icosahedral lipid-containing double-stranded (ds) deoxyribonucleic acid (DNA) bacteriophages have been studied: PRD1, Bam35 and P23-77. The work focuses on the entry, exit and structure of the viruses. PRD1 is the type member of the Tectiviridae family, infecting a variety of Gram-negative bacteria. The PRD1 receptor binding complex, consisting of the penton protein P31, the spike protein P5 and the receptor binding protein P2 recognizes a specific receptor on the host surface. In this study we found that the transmembrane protein P16 has an important stabilization function as the fourth member of the receptor binding complex and protein P16 may have a role in the formation of a tubular membrane structure, which is needed in the ejection of the genome into the cell. Phage Bam35 (Tectiviridae), which infects Gram-positive hosts, has been earlier found to resemble PRD1 in morphology and genome organization The uncharacterized early and late events in the Bam35 life cycle were studied by electrochemical methods. Physiological changes in the beginning of the infection were found to be similar in both lysogenic and nonlysogenic cell lines, Bam35 inducing a temporal decrease of membrane voltage and K+ efflux. At the end of the infection cycle physiological changes were observed only in the nonlysogenic cell line. The strong K+ efflux 40 min after infection and the induced premature cell lysis propose that Bam35 has a similar holin-endolysin lysis system to that of PRD1. Thermophilic icosahedral dsDNA Thermus phages P23-65H, P23-72 and P23-77 have been proposed to belong to the Tectiviridae family. In this study these phages were compared to each other. Analysis of structural protein patterns and stability revealed these phages to be very similar but not identical. The most stable of the studied viruses, P23-77, was further analyzed in more detail. Cryo-electron microscopy and three-dimensional image reconstruction was used to determine the structure of virus to 14 Å resolution. Results of thin layer chromatography for neutral lipids together with analysis of the three dimensional reconstruction of P23-77 virus particle revealed the presence of an internal lipid membrane. The overall capsid architecture of P23-77 is similar to PRD1 and Bam35, but most closely it resembles the structure of the capsid of archaeal virus SH1. This complicates the classification of dsDNA, internal lipid-containing icosahedral viruses.
  • Hietarinta, Elina (2015)
    Oats is one of the most cultivated grains in the world. Oat contains 5 to 8 % of lipids, which is a lot compared to many other cereals. Most of the oat lipids are triacylglycerols and about 80 % of its fatty acids are nutritionally significant unsaturated fatty acids. Due to high fat content and high amount of unsaturated fatty acids both the processing of oats and the development of new oat products are challenging. Oat lipids and their reactions during the processing and storage are a significant reason for the changes in oat quality and the unpleasant flavour. It is possible to either decrease or increase the stability of lipids with different processing methods. The objective of this study was to examine oat lipid reactions and stability during the storage. Ravintoraisio Oy gave all the samples for the research. There were seven oat products, which all were differently processed. Samples of different ages of these products were analysed. Short-term storage test was made for four samples, over 16 weeks at 40 °C. At first, all the oat samples were milled to small particles and then total lipids of these products were extracted by accelerated-solvent-extraction. Neutral lipid classes, volatile compounds and tocols were measured from the samples. Neutral lipid classes were analysed by the high performance liquid chromatography method with evaporative light scattering detector. Volatile compounds were measured by a solid phase microextraction method with GC-MS. Tocols were measured by the high performance liquid chromatography method with fluorescence detector. All the oat samples contained about 5 % of lipids. Most of the lipids were still triacylglycerols after a long-term storage. Free fatty acids were detected only from non-heat-treated samples. Content of tocols decreased significantly in oat samples during storage. Tocol content decreased when degree of processing rose. The content of oxidation products of oat lipids, like hexanal, also rose during the storage. Hexanal and 2-pentylfuran were the most abundant volatiles in the samples. The highest amount of oxidation products were found in extrudates which were stored for 16 weeks at 40 °C. Based on the results, storing oat products for 16 weeks at 40°C, corresponds with over one year storage at natural storage temperature. The effects of extrusion and heat treatment have strong influence on reactions of oat lipids and storage stability. The lipids of unprocessed oat grains were the most stable. More information is required to identify the exact reason for off-odors and off-flavours.
  • Vainio, Saara (Helsingin yliopisto, 2006)
  • Tigistu-Sahle, Feven (2012)
    In addition to being structural components of biological membranes and energy storage of cells, lipids have recently been found to participate as essential players in cell signaling, subcellular transport mechanisms, adjusting functions of integral proteins, and regulation of cell growth and apoptosis. In this study electrospray ionization mass spectrometry (ESI-MS) techniques were used to analyze the phospholipid composition of human bone marrow derived mesenchymal stem cells (BMSC). Numerous chemically distinct lipid species were quantified and the changes in their relative amounts i.e. in the cell’s lipid profile after sequential passaging were followed until senescence (usually from passage 4 up to passage 10, in some cases until p14). Subsequently, the total lipids extracted from the cell pellets were analyzed by triple quadrupole ESI-MS equipment and using lipid-class specific scanning modes. The BMSC lines studied originated from ten donors, five of which were young and five elderly individuals. In culture, the BMSC from both young and aged donors showed time-dependent changes in their phospholipid profiles. The clearest marker findings among individual lipid species were that in phosphatidylcholines (PC) and phosphatidylethanolamines (PE), the species 38:4 (acyl chain pair 18:0/20:4n-6) largely increased towards the late passages, which was seen in the BMSC derived from both the young or aged donors. Thus the reserves of 20:4n-6, the precursor of the eicosanoids having antiproliferative, apoptotic and inflammatory cellular reactions, were increased towards late passages. At phospholipid class level, lysophosphatidylcholine (LysoPC) and phosphatidylinositol (PI) totals, and the ratio of total PI to total phosphatidylserine (PI:PS) were increased from early to latest passages. The results provide new lipid biomarkers to be used for stem cell quality control. The accumulation of polyunsaturated lipid species containing 20:4n-6 or the increase of PI: PS ratio could be potential markers for cell aging and the cells’ poor viability and functionality. The results can be used to develop efficient stem cell therapies and improve patient safety.
  • Tolonen, Nina (Helsingin yliopisto, 2015)
    Background: Cardiovascular disease is the most common cause of death in patients with type 1 diabetes, and the premature mortality rates are especially high in patients with diabetic nephropathy. Diabetic retinopathy is the leading cause of vision loss among the working-age population in industrialized countries. Early identification and aggressive treatment of risk factors are crucial to reduce the incidence of diabetic complications. Aims: To examine the relationships between lipid profiles and diabetic nephropathy, diabetic retinopathy, and incident coronary artery disease (CAD) events in a large nationwide cohort of patients with type 1 diabetes. Subjects and methods: These studies are part of the ongoing Finnish Diabetic Nephropathy Study (FinnDiane). Studies I (N=2927) and III (N=1465) have a cross-sectional design. At follow-up, renal status was verified by a review of all available medical files (Study II, N=2304), and data on CAD events were retrieved from the Finnish Hospital Discharge Register and the Causes of Death Register (Study IV, N=3520). Results: The recommended lipid concentrations of current treatment guidelines were poorly met, especially regarding the target for LDL cholesterol. Triglycerides and apolipoprotein (Apo) B were independent predictors of progression to micro- and macroalbuminuria, and total cholesterol was an independent predictor of progression to end-stage renal disease. HDL and HDL2 cholesterol were independently associated with proliferative diabetic retinopathy (PDR). In patients with PDR, the correlations between albumin excretion rate (AER) and lipid variables were strong. However, in patients without retinopathy no significant correlations were observed. In multivariate models, ApoB, triglycerides, non-HDL cholesterol, ApoB/ApoA-I ratio, and triglyceride/HDL cholesterol ratio were the strongest lipid predictors of an incident CAD event. Conclusions: Lipid abnormalities were associated with an increased risk of all three diabetic complications studied, i.e. diabetic nephropathy, retinopathy, and incident CAD events. Triglycerides and ApoB were independently associated with AER and estimated glomerular filtration rate (eGFR) and predicted the progression to micro- and macroalbuminuria as well as incident CAD events. Far lower concentrations of triglycerides than the currently recommended cut-off level (less than 1.7 mmol/l) increased the risk of progression of renal disease. Total and LDL cholesterol were poor predictors of an incident CAD event in patients with normal AER, in patients with HbA1c below the median (8.3%, 67mmol/l) of the cohort, and in women, in whom the ratios of atherogenic and anti-atherogenic lipoproteins and lipids performed better. Current treatment recommendations may need to be revised to reflect residual CAD risk in patients with type 1 diabetes.
  • Pöhö, Päivi (2013)
    Lipidomics or global lipid profiling is a branch of metabolomics that aims to comprehensive analysis of lipids in a biological system. Lipidomics has become an important research field, since the increased awareness of lipid functions in cell and their role in many common diseases. Also the development of analytical methods, especially mass spectrometry has driven the progress of lipid profiling methods. Lipid profiling allows detection and quantitation of hundreds of intact lipid species in parallel. Challenges in lipidomics are the diversity of different lipid structures and varying lipid concentrations in biological samples. Despite of the development of lipidomics there is not yet a single analytical method to screen all lipids in a biological system. Therefore targeted lipidomics methods are needed in addition to global lipidomics. The literature part of this study presents different analytical methods used in lipidomics studies. The most popular lipid profiling methods are liquid chromatography-mass spectrometry (LC-MS) and direct infusion mass spectrometry or so called shotgun analysis. LC-MS based methods usually utilize reversed phase columns including octadecylsilane stationary phases, but also normal phase chromatography has been applied. In shotgun lipidomics crude extracts are infused directly to mass spectrometer without prior separation. In lipidomics, both unit resolution mass spectrometers like triple quadrupole and ion trap as well as high mass accuracy mass spectrometers like Fourier transform ion cyclotron resonance, Orbitrap, and time of flight mass spectrometers have been used. Mass scanning methods have provided full scan acquisition with accurate mass as well as tandem mass spectrometry like precursor ion scan, neutral loss scan, and multiple reaction monitoring. From the atmospheric pressure ionization techniques, electrospray ionization has been the most applied ionization, but also other soft ionization techniques such as matrix-assisted laser desorption/ionization has been employed. Sample pretreatment in global lipid profiling relies on homogenization and extraction with chloroform-methanol. The most used extraction methods are Folch and Blight and Dyer extractions or modifications of these. In addition, other sample pretreatment methods like solid phase extraction, derivatization, and thin layer chromatography have been used, especially with targeted lipidomics methods. Lipidomics platforms have been applied to several studies of different diseases like diabetes, schizophrenia, and cancer. Many bioactive signaling lipids cannot be detected with lipid profiling methods, since they exist at low concentration and have polar structure. In the experimental part a targeted method was developed for analysis of signaling lipids by ultrahigh-performance liquid chromatography-mass spectrometry. Selected compounds were lysophosphatidic acid, sphingosine-1-phosphate, and phosphoinositides. Method development was mainly done with triple quadrupole mass spectrometer, but also Orbitrap was applied. Several different columns, eluent systems, and pretreatment methods were tested, as well as direct infusion. The best chromatographic separation to signaling lipids was achieved with a reversed phase column at alkaline conditions. However, with this method also several drawbacks were encountered. Peaks were shifting and broadening, there were carryover effects, and problems with repeatability and sensitivity. Direct infusion on the contrary turned out to be problematic because of the unstable electrospray and formation of lysophosphatidic acid from lysophosphocholine in the ionization chamber. Development of a single analytical method for these signaling lipids turned out to be a challenging task and a complete working method for all the studied compounds was not attained.
  • Kallio, Elisa (Helsingin yliopisto, 2014)
    Periodontitis is characterized by an inflammatory response to bacterial infection in the supporting tissues of the teeth. The disease manifests with gingival swelling and bleeding, increased periodontal pocket depth, and alveolar bone loss. Intact bacteria or bacterial products, including lipopolysaccharide (LPS), may enter the bloodstream through inflamed periodontal tissue or via saliva. Bacterial dissemination, further potentiated by gastrointestinal microbiota, may result in endotoxemia and low-grade inflammation. The general aim of this thesis research was to investigate whether LPS links periodontitis with cardiometabolic disorders. The following topics were studied: genetic factors associated with the susceptibility to periodontitis, the systemic effects of endotoxemia induced by periodontitis and cardiometabolic disorders, as well as the influence of periodontal treatment on plasma LPS activity and lipoprotein composition. A study of genetic polymorphisms of the human major histocompatibility complex region demonstrated that a haplotype comprising six SNPs of the BAT1, NFKBIL1, and LTA genes was associated with the risk of having periodontitis. The risk haplotype showed an association with bleeding on probing, probing pocket depth ≥6 mm, and severe periodontitis, and the result was replicated in two different study populations with concordance. In addition, the serum lymphotoxin-α (LTA) concentration was associated with LTA SNPs of the risk haplotype in homozygous patients, and LTA was expressed in the inflamed periodontal tissue. The systemic effects of the periodontitis-derived endotoxemia were investigated before and after periodontal treatment. In the serum of periodontitis patients, LPS was associated with the proatherogenic very low-density lipoprotein intermediate-density lipoprotein (VLDL-IDL) fraction. Although local healing of the periodontium was successful, the systemic inflammation status of the patients failed to improve after periodontal treatment, reflecting the complexity and persistence of the disease. There were no significant changes in plasma LPS activity or its distribution among lipoprotein classes after periodontal treatment. However, the VLDL of patients with severe periodontitis induced higher expression of proinflammatory cytokines in macrophages when compared with VLDL derived from patients with moderate periodontitis. In addition, VLDL isolated from patients with severe periodontitis with suppuration contained more LPS and induced higher cholesterol uptake in macrophages. The effect of nutrient intake on the association of serum LPS activity with cardiometabolic disorders was examined in a population-based cohort. Endotoxemia was strongly associated with prevalent obesity, metabolic syndrome (MetS), diabetes, and coronary heart disease (CHD). In addition, high serum LPS activity was associated with an increased risk of future CHD events. Even though energy intake was correlated with LPS activity in lean, healthy subjects, the general associations were independent of energy or macronutrient intake. The results indicate that genetic variation in the MHC class III region may be important in periodontitis susceptibility. Endotoxemia and low-grade inflammation originating from periodontitis may induce the proatherogenic properties of VLDL particles via macrophage activation and foam cell formation, thereby promoting atherogenesis. The association of obesity, MetS, diabetes, and CHD with endotoxemia supports the significance of bacterial infections and the immune response in the etiology of cardiometabolic disorders. In conclusion, the findings highlight the close relationship between genetics, the immune response, and lipid metabolism, promoting the role of LPS as a link between periodontitis and cardiometabolic disorders.
  • Tepora, Tuomas (2011)
    This dissertation deals with the notions of sacrifice and violence in connection with the Fin¬nish flag struggles between 1917 and 1945. The study begins with the basic idea that sacrificial thinking is a key element in nationalism and the social cohesion of large groups. The method used in the study combines anthropological notions of totemism with psychoanalytical object relation theory. The aim is to explore the social and psychological elements of the Finnish national flag and the workers flags during the times of crisis and nation building. The phenomena and concepts addressed include self-sacrifice, scapegoating, remembrance of war, inclusion, and exclusion. The research is located at the intersection of nationalism studies and the cultural history of war. The analysis is based primarily on the press debates, public speeches and archival sources of the civic organizations that promoted the Finnish flag. The study is empirically divided into three sections: 1) the years of the Revolution and the Civil War (1917 1918), 2) the interwar period (1919 1938), and 3) the Second World War (1939 1945). The research demonstrates that the modern national flags and workers flags in Finland maintain certain characteristics of primitive totems. When referred to as a totem the flag means an emotionally charged symbol, a reservoir of the collective ideals of a large group. Thus the flag issue offers a path to explore the perceptions and memory of sacrifice and violence in the making of the First Republic . Any given large group, for example a nation, must conceptually pursue a consensus on its past sacrifices. Without productive interpretation sacrifice represents only meaningless violence. By looking at the passions associated with the flag the study also illuminates various group identities, boundaries and crossings of borders within the Finnish society at the same time. The study shows further that the divisive violence of the Civil War was first overcome in the late 1930s when the social democrats adopted a new perception of the Red victims of 1918 they were seen as part of the birth pains of the nation, and not only the martyrs of class struggle. At the same time the radical Right became marginalized. The study also illuminates how this development made the Spirit of the Winter War possible, a genuine albeit brief experience of horizontal brother and sisterhood, and how this spirit was reflected in the popular adoption of the Finnish flag. The experience was not based only on the external and unifying threat posed by the Soviet Union: it was grounded in a sense of unifying sacrifice which reflected a novel way of understanding the nation and its past sacrifices. Paradoxically, the newly forged consensus over the necessity and the rewards of the common sacrifices of the Winter War (1939 1940) made new sacrifices possible during the Continuation War (1941 1944). In spite of political discord and war weariness, the concept of a unified nation under the national flag survived even the absurdity of the stationary war phase. It can be said that the conflict between the idea of a national community and parliamentary party politics dissolved as a result of the collective experience of the Second World War.
  • Tepora, Tuomas (Helsingin yliopisto, 2004)
    Tutkielma käsittelee Suomen lippua toteemina. Ajallisesti tutkimus sijoittuu itsenäisyyden ajan alkuun. Työn teoreettinen lähtökohta on idea kansallislipusta kansakunnan itseensä kohdistuvan palvonnan merkkinä. Tutkielmassa tarkastellaan lippuun liittyvän veriuhrin ja uhrivalmiuden merkitystä suomalaisen kansakunnan rakentamisessa: uhrien kautta kansakunta saa elinvoimaa ja lippu liehuu suoritetun uhrin merkkinä. Tutkielman aluksi käsitellään nationalismitutkimusta ja kansallisuusaatteen traditioita sekä pohditaan lipputotemismin teoriaa. Toteemi pyrkii sisällyttämään itseensä koko yhteiskunnan: ihmisten tavoitellessa tiettyä objektia he sisäistävät itseensä sen ideaalit. Työn empiirinen osuus käsittää vuosina 1917-1918 julkisuudessa ja eduskunnassa käydyn keskustelun Suomen lipun väreistä ja merkityksestä. Ennen kansalaissotaa etenkin suomenkielisen maaseutuväestön kannattama sinivalkoinen väriyhdistelmä oli suuresta kannatuksestaan huolimatta puolustusasemissa virallisia vaakunavärejä vastaan, mutta vuoden 1918 tapahtumat muuttivat asetelman. Punainen väri sai väistyä, mutta punalipun pelko ei ollut ainoa asiaa selittävä tekijä. Etenkin nuori suomenkielinen sivistyneistö, joka oli kannattanut punakeltaisia värejä, palasi sodan jälkeen isiensä sinivalkoiseen perinteeseen. Taustalla oli syyllisyys: sinivalkoinen edusti paluuta idealistiseen ja harmoniseen esiseksuaaliseen tilaan punakeltaisen liehuessa hyökkäävän ja yksilöllisen materialismin merkkinä. 1920-luvulla työväestö ryhmittyi punalipun perään sosialidemokraattien noustessa vaa'ankieliasemaan heidän omaksuessaan valtakunnanlipun osaksi järjestötomintaansa vuonna 1927; kansallinen lippukulttuuri alkoi vähitellen kehittyä liputuskäytäntöjen vakiintuessa. Valtion ja sen laitosten sekä kuntien harjoittaman virallisen liputuksen ohella kahden kansalaisjärjestön lipputyö oli merkityksellistä. Itsenäisyyden Liitto ja Suomalaisuuden Liitto pyrkivät levittämään Suomen lippuja ja lipun sanomaa maan eri puolille. Itsenäisyyden Liitto nousi 1920-luvun lopulla tärkeimmäksi järjestöksi, sillä sille lippuasia oli todellinen pakkomielle. Liiton toiminta heijastaa totemismin teoriaa hyvin: lipun sanattomien ideaalien omaksuminen oli ainoa kansaa eheyttävä tekijä, koko valtakuntaa peittävä yhtenäinen lippumeri todiste yhteiskunnallisesta ja kieliriidattomasta yksimielisyydestä. Liiton sanoma kuului lyhyesti: kuoleminen lipun vaatimien arvojen - yksimielisen ja eheän kansan - puolesta oli itsestäänselvää, vaikeampaa oli elää oikealla tavalla vailla puolueriitojen sävyttämiä yksilöllisen itsekeskeisiä pyyteitä vain kansakokonaisuutta palvellen. Itsenäisyyden Liitto kehitti eteenpäin 1920-luvun puolivälissä esitettyä ideaa erityisestä Suomen lipun päivästä, joka sijoitettiin juhannukseksi. Ensimmäisen kerran lippupäivää vietettiin vuonna 1927 ja seuraavasta vuodesta lähtien liitto järjesti juhannuksena lippujuhlia ympäri maata. Itsenäisyyspävänä liitto järjesti virallisen lipunnostoseremonian Helsingissä Tähtitorninmäellä vuodesta 1928 alkaen. 1920- ja 30-lukujen vaihteessa lapuanliike ja työväentalojen pakkoliputukset sekä kommunistien aktivoitunut toiminta kärjistivät toteemien suhteet, mutta ilmiö oli monessa mielessä viimeinen kouristus ennen lipputoteemien suhteiden lientymistä, joka alkoi 1930-luvun puolivälissä. Tutkielman lähdeaineistona on käytetty tarkasteltujen järjestöjen arkistokokoelmia, laajasti lehdistöä sekä aikalaiskirjallisuutta. Oman osansa muodostavat valtiopäiväasiakirjat. Avainsanat: Suomen lippu, lippukulttuuri, totemismi, uhri, nationalismi
  • Hakala, Kati (Helsingin yliopisto, 2008)
    Poor pharmacokinetics is one of the reasons for the withdrawal of drug candidates from clinical trials. There is an urgent need for investigating in vitro ADME (absorption, distribution, metabolism and excretion) properties and recognising unsuitable drug candidates as early as possible in the drug development process. Current throughput of in vitro ADME profiling is insufficient because effective new synthesis techniques, such as drug design in silico and combinatorial synthesis, have vastly increased the number of drug candidates. Assay technologies for larger sets of compounds than are currently feasible are critically needed. The first part of this work focused on the evaluation of cocktail strategy in studies of drug permeability and metabolic stability. N-in-one liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods were developed and validated for the multiple component analysis of samples in cocktail experiments. Together, cocktail dosing and LC/MS/MS were found to form an effective tool for increasing throughput. First, cocktail dosing, i.e. the use of a mixture of many test compounds, was applied in permeability experiments with Caco-2 cell culture, which is a widely used in vitro model for small intestinal absorption. A cocktail of 7-10 reference compounds was successfully evaluated for standardization and routine testing of the performance of Caco-2 cell cultures. Secondly, cocktail strategy was used in metabolic stability studies of drugs with UGT isoenzymes, which are one of the most important phase II drug metabolizing enzymes. The study confirmed that the determination of intrinsic clearance (Clint) as a cocktail of seven substrates is possible. The LC/MS/MS methods that were developed were fast and reliable for the quantitative analysis of a heterogenous set of drugs from Caco-2 permeability experiments and the set of glucuronides from in vitro stability experiments. The performance of a new ionization technique, atmospheric pressure photoionization (APPI), was evaluated through comparison with electrospray ionization (ESI), where both techniques were used for the analysis of Caco-2 samples. Like ESI, also APPI proved to be a reliable technique for the analysis of Caco-2 samples and even more flexible than ESI because of the wider dynamic linear range. The second part of the experimental study focused on metabolite profiling. Different mass spectrometric instruments and commercially available software tools were investigated for profiling metabolites in urine and hepatocyte samples. All the instruments tested (triple quadrupole, quadrupole time-of-flight, ion trap) exhibited some good and some bad features in searching for and identifying of expected and non-expected metabolites. Although, current profiling software is helpful, it is still insufficient. Thus a time-consuming largely manual approach is still required for metabolite profiling from complex biological matrices.
  • Uutela, Päivi (Helsingin yliopisto, 2009)
    Neurotransmitters transfer chemically the electrical impulse from one neuron to another in the brain. The concentration of neurotransmitters in many neurological disorders is altered. The measurement of neurotransmitters in the brain is needed to understand how these diseases develop and how they can be treated. Neurotransmitters can be extracted from the brains of freely moving, alert animals by microdialysis technique. The concentration of neurotransmitters and their metabolites in brain microdialysates is low, and therefore highly sensitive and specific analytical methods are needed. The aim of this study was to develop such liquid chromatography-electrospray-tandem mass spectrometric (LC-ESI-MS/MS) methods for the analysis of neurotransmitters in brain microdialysates. Neurotransmitters and their metabolites are known to form sulfate and glucuronide conjugates in the brain. However, only non-specific indirect analysis methods employing acid or enzyme hydrolysis have been used in the analysis of brain and cerebrospinal fluid (CSF) samples. In this work sulfate and glucuronide conjugates of dopamine and serotonin, and their phase I metabolites were synthesized for reference compounds. With LC-MS/MS method developed the regioisomers of conjugates could be detected, which has not been possible with indirect methods. In this study, the serotonin and dopamine glucuronides was discovered in rat and mouse brain microdialysates for the first time. It was observed that neurotransmitters were glucuronidated while their acidic phase I metabolites were sulfated. The analysis of gamma-aminobutyric acid (GABA) in rat brain microdialysates by LC-MS has been problematic due to high LODs. In this study amino acids were derivatized to enhance their retention on reversed phase chromatography and ESI. Three different commonly used derivatization reagents (propyl chloroformate, butanol and 9-fluorenylmethyl chloroformate) were compared in the analysis of amino acids by LC-MS/MS. The limits of detection (LOD) for derivatives were 2-60 times lower than for native underivatized amino acids. After propyl chloroformate derivatization, GABA and nine other amino acids could be easily quantified in rat brain microdialysates by LC-MS/MS. In the analysis of acetylcholine (Ach) and choline, hydrophilic interaction liquid chromatography (HILIC) was utilised. In HILIC polar stationary phases are used and the retention of polar compounds increases with increasing organic solvent content. The high concentration of ACN (80 %) in the eluent was favourable to ESI enabling sensitive analysis of Ach. The limit of quantification (LOQ) for Ach was 0.1 nM, which allowed the analysis of Ach in rat and mouse brain microdialysates without the use of acetylcholinesterase inhibitors.
  • Jäntti, Sirkku (Helsingin yliopisto, 2013)
    Steroids are endogenous compounds, which are present in the body tissues and fluids in free and conjugated forms, e.g. as steroid glucuronide conjugates. First goal of the study was to develop methodologies for the synthesis of steroid glucuronides. An enzyme-assisted synthesis was carried out to produce glucuronide-conjugated steroids at milligram levels. Hepatic microsomal preparations of bovine, porcine, and Arochlor-induced rats were compared with respect to specificity and efficiency of uridine diphosphate glucuronosyl transferase (UGT) enzymes in steroid glucuronidation. Both bovine and porcine liver microsomes efficiently produced the steroid glucuronides of all eight steroids studied, whereas rat liver microsomes produced glucuronides efficiently only for three steroids. Synthesized steroid glucuronides were purified with solid-phase extraction (SPE) or LC fractionation and characterized by nuclear magnetic resonance spectroscopy (NMR), liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high resolution MS. Steroid glucuronides were obtained in milligram amounts with good yields. The synthesised glucuronides were used in method development and as reference material in the analysis. As a second goal of the study, two methods were developed, one for brain samples using capillary liquid chromatography-electrospray-tandem mass spectrometry (CapLC-ESI-MS/MS) and the other for the urine samples using ultra performance liquid chromatography-electrospray-tandem mass spectrometry (UPLC-ESI-MS/MS).The methods were carefully optimized to obtain good selectivity and maximum sensitivity. Linear range of 3-4 magnitudes was obtained (R2> 0.996) with good precision (RSD < 15%). Detection limits of 6-100 pmol/l were obtained for steroid glucuronides, 10-30 pmol/l for steroid sulphates and 0.03-22 nmol/l for free steroids, respectively. The developed methods were applied to the analysis of mouse brain extracts, to study in vitro metabolism of steroids in rat and mouse brain, and to the analysis of free and glucuronide conjugated steroids during pregnancy. Using the CapLC-MS/MS method steroid glucuronides were observed for the first time in brain. The UPLC-MS/MS method employed in determination of urinary profiles of steroids and steroid glucuronide conjugates steroids during pregnancy. The concentrations of 36 targeted steroids and steroid glucuronides as well as the mostly unidentified C21-steroid glucuronides clearly altered during the pregnancy. In general, the concentrations of the steroids and steroid glucuronides gradually increased during pregnancy, decreased rapidly just before or during delivery, and returned to control sample level five days after the delivery.
  • Inkinen, Tuomas (2002)
    Pro gradu –tutkielmassani tutkitaan listautumisantien alihinnoittelua. Listautumisantien alihinnoittelu on eräs pääomamarkkinoiden tunnetuimmista anomalioista. Alihinnoittelu ilmenee osakkeen ensimmäisen kaupankäyntipäivän epänormaalin suurina tuottoina. Listautuvalle yritykselle alihinnoittelusta on se haitta, että siltä jää saamatta pääomia, jos osakkeet myydään alihintaan. Sijoittajat taas ovat tyytyväisiä, jos he saavat suuria tuottoja heti ensimmäisenä kaupankäyntipäivänä. Listautumisannin järjestäjän, joka useimmiten on investointipankki tai pankkiiriliike, vaikeaksi tehtäväksi jää hinnoitella anti siten, että sekä sijoittajat että liikkeeseenlaskija pysyvät tyytyväisinä. Yksittäinen yritys listautuu vain kerran, kun taas järjestäjä toimii järjestäjänä useissa anneissa, näin ollen järjestäjän on ajateltava myös omaa mainettaan hinnoitellessaan listautumisia. Alihinnoittelulle on tarjottu monenlaisia selityksiä. Tässä tutkielmassa käydään aluksi lyhyesti läpi tunnettuja selityksiä, joita ovat: epäsymmetrinen informaatio, signalointi, järjestäjän maine, kallis informaation kerääminen, lumipalloilmiö, oikeudellinen vastuu, valvojien rajoitukset, hyvinvoinnin uudelleenjako, omistajien hajautus, markkinoiden epätäydellisyys ja stabilointi. Tämän jälkeen keskitytään epäsymmetrisestä informaatiosta johtuviin erilaisiin selityksiin. Tärkeimpiä epäsymmetrisen informaation teorian kehittäjiä on ollut Kevin Rock, jonka malli käydään tässä tutkielmassa läpi. Myös Carterin ja Manasterin malli järjestäjän maineen vaikutuksesta alihinnoitteluun käydään tarkemmin läpi. Tutkielman lopussa on empiirinen tutkimus Helsingin Pörssissä vuosina 1995-2000 tapahtuneista listautumisista ja niiden alihinnoittelusta. Havaitaan, että keskimääräinen ensimmäisen kaupankäyntipäivän tuotto eli alihinnoittelu vuosina 1995–2000 oli noin 25 prosenttia, kun aiemmassa Keloharjun tutkimuksessa vuosilta 1984-1992 Helsingin Pörssissä esiintyi noin 14:sta prosentin alihinnoittelua. Tutkielma ei pysty tarjoamaan mitään tiettyä yksittäistä selitystä alihinnoittelulle, koska kaikki listautumisanteja koskeva informaatio ei ole julkisesti saatavilla. Helsingin Pörssin alihinnoittelun kasvua voidaan selittää vuonna 1999 alkaneella teknologiabuumilla, joka lisäsi listautumisten määrää huomattavasti. Teknologiabuumiin liittynyt ylikysyntä sai ensimmäisen kaupankäyntipäivän tuotot kasvamaan valtavasti. Lopputuloksena todetaan, että myös epäsymmetrisestä informaatiosta aiheutuvat moninaiset tekijät ovat hyvin merkittävä syy alihinnoittelulle.