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  • Backman, Marie (Helsingin yliopisto, 2012)
    Ion irradiation is used to analyze and modify the structure of condensed matter. It can for instance be used to form and shape nanocrystals in solids. In research on materials for high radiation environments, ion beams function as a controlled source of irradiation for studying the basic mechanisms of ion-solid interactions and for analyzing the structure of materials by methods like Rutherford backscattering spectrometry. Understanding the fundamental processes that take place in a material under ion irradiation is important for all these applications of ion beams, and of great interest from a basic science point of view. The mechanisms involved during ion irradiation-induced displacement of atoms in uniform bulk solids are fairly well understood and described in the literature, but many unresolved questions remain regarding the structural modification caused by electronic interactions, and the radiation response of materials with phase boundaries. Especially ion irradiation of nanomaterials is a topic that is under active research. The short-lived collision cascades caused by energetic ions in solids cannot be studied in experiments and are therefore often modeled in computer simulations. Such simulations can give a host of valuable information about processes that occur in nature. It is necessary to validate simulation results by either some other computational method, or ideally by experiments. Ions lose energy by elastic collisions with the atomic nuclei as well as to the electronic system through excitation and ionization. Both energy loss mechanisms - nuclear and electronic stopping - can cause modifications to the structure of the material. In this thesis, molecular dynamics simulations are carried out in close collaboration with experimental scientists in order to study the effects of nuclear and electronic stopping during ion irradiation on nanoclusters and bulk materials. The amorphization of germanium and silicon nanocrystals in silica under ion irradiation is studied in simulations. The amorphization dose of nanocrystals is much lower than for bulk materials and it is furthermore found to depend on the size of the nanocrystals. The inelastic thermal spike model is explored as a method of incorporating electronic stopping effects into molecular dynamics. The simulations predict that local heating due to electronic stopping contributes to irradiation damage in both nanocrystals in silica and bulk silica. In silicon carbide, high electronic stopping is found to recrystallize irradiation damaged samples. Molecular dynamics simulations of inelastic thermal spikes support the hypothesis that the observed recrystallization is induced by local heating due to electronic stopping. We need a combination of computer simulations and experimental observations to explain many of the complex processes that take place during ion irradiation. The results in this thesis give insight into some experimentally observed phenomena of the effect that nuclear and electronic energy loss have in materials, but especially the research on combined effects is still in its infancy and further progress can be expected in the near future.
  • Mildh, Leena (Helsingin yliopisto, 2007)
    Opioids are most commonly used for treatment of severe pain. However, the fear of respiratory depression has restricted the use of opioids. Depending on the monitoring system used, different modes of opioid respiratory effects have been noted in previous studies. All opioids also cause alterations in hemodynamics at least to some extent. The main goal of this series of investigations was to elucidate the native ventilatory and hemodynamic effects of different opioids. Studies I-IV each involved 8 healthy male volunteers. Study V involved 13 patients with lower or upper extremity traumas. The opioids studied were morphine, oxycodone, pethidine, fentanyl, alfentanil, tramadol and ketamine. The respiratory parameters used in this study were breathing pattern measured with respiratory inductive plethysmography, gas exchange measured with indirect calorimetry, blood gas analysis and pulse oximetry. Hemodynamics was measured with arterial blood pressure, heart rate and oxygen consumption. Plasma catecholamine and histamine concentrations were also determined. All opioids studied caused an alteration in respiratory function. Respiratory rate, alveolar ventilation and minute ventilation decreased, while tidal volume increased in most situations. Breathing pattern was also significantly affected after opioid administration. The respiratory depression caused by oxycodone was deeper than the one caused by same dose of morphine. An equianalgesic dose of tramadol caused markedly smaller respiratory depression compared to pethidine. The potency ratio for respiratory depression of fentanyl and alfentanil is similar to analgesic potency ratio studied elsewhere. Racemic ketamine attenuated the respiratory depression caused by fentanyl, if measured with minute ventilation. However, this effect was counteracted by increased oxygen consumption. Supplemental oxygen did not offer any benefits, nor did it cause any atelectasis when given to opioid treated trauma patients. Morphine caused a transient hemodynamic stimulation, which was accompanied by an increase in oxygen consumption. Oxycodone, alfentanil, fentanyl, tramadol and pethidine infusions had minimal effects on hemodynamics. Plasma catecholamine concentrations were increased after high dose opioid administration. Plasma histamine concentrations were not elevated after morphine nor oxycodone administration. Respiratory depression is a side effect noted with all opioids. The profile of this phenomenon is quite similar with different opioid-receptor agonists. The hemodynamic effects of opioids may vary depending on the opioid used, morphine causing a slight hemodynamic stimulation. However, all opioids studied could be considered hemodynamically stable.
  • Louhelainen, Marjut (Helsingin yliopisto, 2010)
    Suun kautta annosteltava kalsiumherkistäjä parantaa sydämen vajaatoimintaan liittyvää pumppausvajetta kokeellisissa sydämen vajaatoimintamalleissa Huolimatta viime vuosikymmenien lääketieteellisestä kehityksestä krooninen sydämen vajaatoiminta on silti edelleen vakava, elämänlaatua voimakkaasti rajoittava sairaus. Kalsiumherkistäjät ovat uusi, sydämen pumppausvoimaa lisäävä lääkeryhmä. Levosimendaani, kotimaista alkuperää oleva kalsiumherkistäjä, on kliinisessä käytössä akuutin vajaatoiminnan hoitoon suonensisäisesti ja lyhytaikaisesti annosteltavana valmisteena. Levosimendaanilla on aktiivinen metaboliitti, OR-1896, jonka oletetaan olevan vuorokauden mittaisen levosimendaani-infuusion jälkeen havaittujen useita päiviä kestävien hyödyllisisten vaikutuksisten takana. Levosimendaanin kroonisen, suun kautta tapahtuvan annostelun vaikutuksista tieto on vähäisempää, mutta sillä näyttää olevan positiivisia vaikutuksia potilaiden raportoimana. FM Marjut Louhelainen on selvittänyt väitöskirjassaan suun kautta annosteltavan levosimendaanin ja sen pitkäkestoisen aktiivisen metaboliitin vaikutuksia kroonisen vajaatoiminnan hoidossa käyttämällä sekä hypertensiivisen sydäntaudin että 2 tyypin diabeteksen komplisoimaan sydäninfarktin kokeellisia malleja. Tutkimuksessa selvitettiin lisäksi vajaatoimintaan johtavia molekyylitason tapahtumia sydänlihaksessa. Tutkimuksessa osoitettiin, että krooninen suun kautta annosteltu hoito sekä kalsiumherkistäjä levosimendaanilla että sen aktiivisella metaboliitilla estää hypertensiiviseen sydämen vajaatoiminnan aikaasaamaa sydämen uudelleenmuovaantumista ja siihen liittyvää kuolleisuutta. Nämä vaikutukset välittyivät vähentyneen sydänlihassoluhypertrofian, solukuolleisuuden ja neurohumaraalisen aktivaation kautta. Levosimendaanin ja OR-1896:n osoitettiin myös parantavan sydämen pumppausfunktiota tyyppi 2 diabeteksen komplisoimassa sydäninfarktissa. Ei-diabeettiseen tilanteeseen verrattuna diabetekseen liittyvä infarktin jälkeinen vajaatoiminnan kehitys oli yhteydessä lisääntyneeseen tulehdukseen, fibroosiin, solukuolemaan, neurohumoraaliseen aktivaatioon ja ennenaikaiseen kudoksen vanhenemiseen. Sekä levosimendaani, että OR-1869 vähensivät tulehduksen, fibroosin ja solukuoleman merkkejä ja vaimensi neurohumoraalista aktivaatiota. OR-1896 myös vähensi solujen vanhenemiseen liittyvien merkkiaineiden ilmentymistä. Väitöskirjassa todettiin, että suun kautta annosteltuna sekä levosimendaani, että sen aktiivinen metaboliitti OR-1896, omaavat terapeuttista potentiaalia sekä hypertensiivisen sydäntaudin hoitoon että sydäninfarktin jälkeisen vajaatoiminnan estoon. FM Marjut Louhelaisen farmakologian alaan kuuluva väitöskirja Effects of oral calcium sensitizers on experimental heart failure tarkastetaan Helsingin yliopiston Lääketieteellisessä tiedekunnassa perjantaina 29.01.2010 klo 12 (Biomedicum Helsinki, luentosali 2, Haartmaninkatu 8, Helsinki). Vastaväittäjänä toimii professori Raimo Tuominen, Helsingin yliopiston Farmasian tiedekunnasta ja kustoksena professori Eero Mervaala Helsingin yliopiston Lääketieteellisestä tiedekunnasta.
  • Rintala, Eija (VTT Valtion teknillinen tutkimuskeskus, 2010)
    The availability of oxygen has a major effect on all organisms. The yeast Saccharomyces cerevisiae is able to adapt its metabolism for growth in different conditions of oxygen provision, and to grow even under complete lack of oxygen. Although the physiology of S. cerevisiae has mainly been studied under fully aerobic and anaerobic conditions, less is known of metabolism under oxygen-limited conditions and of the adaptation to changing conditions of oxygen provision. This study compared the physiology of S. cerevisiae in conditions of five levels of oxygen provision (0, 0.5, 1.0, 2.8 and 20.9% O2 in feed gas) by using measurements on metabolite, transcriptome and proteome levels. On the transcriptional level, the main differences were observed between the three level groups, 0, 0.5 2.8 and 20.9% O2 which led to fully fermentative, respiro-fermentative and fully respiratory modes of metabolism, respectively. However, proteome analysis suggested post-transcriptional regulation at the level of 0.5 O2. The analysis of metabolite and transcript levels of central carbon metabolism also suggested post-transcriptional regulation especially in glycolysis. Further, a global upregulation of genes related to respiratory pathways was observed in the oxygen-limited conditions and the same trend was seen in the proteome analysis and in the activities of enzymes of the TCA cycle. The responses of intracellular metabolites related to central carbon metabolism and transcriptional responses to change in oxygen availability were studied. As a response to sudden oxygen depletion, concentrations of the metabolites of central carbon metabolism responded faster than the corresponding levels of gene expression. In general, the genome-wide transcriptional responses to oxygen depletion were highly similar when two different initial conditions of oxygen provision (20.9 and 1.0% O2) were compared. The genes related to growth and cell proliferation were transiently downregulated whereas the genes related to protein degradation and phosphate uptake were transiently upregulated. In the cultures initially receiving 1.0% O2, a transient upregulation of genes related to fatty acid oxidation, peroxisomal biogenesis, response to oxidative stress and pentose phosphate pathway was observed. Additionally, this work analysed the effect of oxygen on transcription of genes belonging to the hexose transporter gene family. Although the specific glucose uptake rate was highest in fully anaerobic conditions, none of the hxt genes showed highest expression in anaerobic conditions. However, the expression of genes encoding the moderately low affinity transporters decreased with the decreasing oxygen level. Thus it was concluded that there is a relative increase in high affinity transport in anaerobic conditions supporting the high uptake rate.
  • Sekhar, Deepa (2012)
    Metabolic disorders are known to predispose dairy cows to periparturient diseases. Main components of metabolic disorder are insulin resistance and severe negative energy balance which are responsible for the reduced fertility in addition of increased risk of disease in dairy cows. The mobilization of adipose tissue in response to energy deficiency is associated with metabolic and endocrine changes during early lactation. Reduced insulin sensitivity in peripheral tissues could potentially change the relative rates of lipolysis and lipogenesis. This study focused on expression of lipogenesis and lipolysis associated genes around parturition. Samples and data sets for this study were obtained from the feeding experiments conducted from September 2010 to April 2011 in Viikki Experimental Farm at the University of Helsinki. Sixteen multiparous Ayrshire cows were divided into two groups based on energy level and fibre content of their feed: (1) grass silage group (control) and (2) silage-roughage mixture group (experiment). During experimental period average energy intake (MJ/day) in silage group was 35% higher than in silage-roughage mixture group. Subcutaneous adipose tissue samples were collected a week before, one day and a week after parturition from cows. Total RNA was extracted from tissue samples quality and quantity of total RNA was analysed using electrophoresis and spectrophotometer. Complementary DNA (cDNA) was prepared from the total RNA for quantitative PCR (qPCR). QPCR was conducted to quantitate expression of the following genes: adiponectin (ADIPOQ), leptin (LEP), peroksisome proliferator activated receptor gamma (PPAR-γ), adiponectin receptor-1 (AR1), adiponectin receptor-2 (AR2), lipoprotein lipase (LPL), stearoyl-CoA desaturase (SCD) and hormone-sensitive lipase (HSL). Two genes, AR2 and LEP, were downregulated in group 1. Reduced expression of AR2 in group 1 may relate to an increased insulin resistance. The glucose metabolism was reduced further leading to reduced insulin sensitivity. Lower expression of LEP after parturition indicates usage of energy for milk production. The upregulation of SCD in group 1 before and after calving as well as after calving in group 2 may be a result of the uptake of fatty acids by the mammary tissues. The expression of ADIPOQ, AR1, LPL, PPAR, and HSL did not show any significant changes.
  • Hautamäki, Hanna (Helsingin yliopisto, 2014)
    Hot flushes, the most characteristic symptoms in menopause, are encountered by c.a. 80% of women. Hot flushes and other menopausal complaints can significantly impair a woman s quality of life. Additionally, the majority of women experience premenstrual symptoms in their fertile age. Due to the resemblance between premenstrual and menopausal symptoms, women with severe premenstrual symptoms might fear for an increased risk of developing menopausal complaints, such as vasomotor symptoms. It is, however, unclear why some women experience intolerable hot flushes while others remain completely asymptomatic. Hot flushes are characterised by cardiovascular reactions such as rapid episodes of reddening of skin and palpitations. Thus, women with or without hot flushes may differ in their cardiovascular reactivity and responses to hormone therapy. The present study was designed to investigate the impact of hot flushes and different forms of hormone therapy on health-related quality of life and cardiovascular autonomic function. Therefore, 150 healthy, recently postmenopausal women showing a large variation in hot flushes were studied before and during six months of hormone therapy. Hot flushes were evaluated prospectively with a two-week hot flush diary. The relationship between a history of premenstrual symptoms and the postmenopausal quality of life and hot flushes was also assessed. The cardiovascular autonomic function was studied with a standardised test series in controlled laboratory settings. Hot flushes were important determinants for the decreased health-related quality of life in menopause. Previous premenstrual symptoms lacked correlation with the severity of postmenopausal hot flushes but associated with deterioration of health-related quality of life, seen as poor sleep, depressive feelings and impaired memory and concentration. Women with hot flushes reacted with more tachycardia and slightly blunted parasympathetic activity in heart rate responses to cardiovascular autonomic testing compared with asymptomatic women. In a randomized study, all hormone therapy regimens alleviated hot flushes and other menopausal symptoms equally effectively. In women with pre-treatment hot flushes, hormone therapy improved health-related quality of life in terms of sleep, anxiety and fears, memory and concentration, and general health. Hot flushes were accompanied with lowered resting blood pressures but increases in blood pressure responses to physical strain during all hormone therapy regimens. Estradiol treatment lowered resting heart rate and reduced maximal heart rate in response to physical strain in women with pre-treatment hot flushes. This beneficial effect on heart rate was attenuated by adding medroxyprogesterone acetate to estradiol treatment. In conclusion, the hot flush status and hormone therapy contribute to cardiovascular autonomic function. Hot flushes seem to associate with slightly pronounced sympathetic responses in autonomic regulation of heart rate and blood pressure, which can be considered unbeneficial for cardiovascular function. This possibly unfavourable sympathetic activity can be reduced with estradiol treatment especially in women with hot flushes, who are potential candidates for hormone therapy in clinical practice. Hot flushes impair the health-related quality of life in recently postmenopausal women, but can be effectively alleviated with hormone therapy. Premenstrual symptoms do not predict severe hot flushes in menopause, which is comforting for women having troublesome premenstrual symptoms.
  • Oksaharju, Anna (Helsingin yliopisto, 2012)
    Mast cells are immunological cells having an important function in host defense. Mast cells also participate in the regulation of many other physiological functions of the body, such as the regulation of tissue homeostasis, intestinal functions, and neuro-immune interactions, by producing multiple mediators including cytokines, chemokines, leukotrienes, prostaglandins, proteases, and biogenic amines. However, these same mast cell-derived mediators are involved in the pathogenesis of many inflammatory diseases, such as atherosclerosis and other metabolic disorders, as well as allergy and intestinal diseases. Considering the inflammatory nature of atherosclerosis, exploring the role of infection in the pathogenesis of the disease has recently gained attention. Components of microbial origin have been detected in atherosclerotic lesions and are suggested to promote the inflammatory status in the arteries. On the other hand, microbes with beneficial effects on human health, called probiotics, have been under extensive study regarding their ability to modulate immunological functions and, thus, their possible benefits in the prevention and alleviation of inflammatory diseases. The purpose of the present study was to investigate the ability of atherosclerosis-related and probiotic bacteria to activate mast cells and their possible effects on inflammation caused by infection or diet. The proatherogenic bacteria Chlamydia pneumoniae (Cpn) and Aggregatibacter actinomycetemcomitans (Aa) induced pro-inflammatory effects in cultured human peripheral-derived mast cells characterized by the elevated expression and secretion of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α), and chemokines, such as interleukin (IL)-8 and chemokine (C-C motif) ligand 2 (CCL-2). Cpn and Aa also increased the number of activated mast cells in the aortas of atherosclerosis-prone ApoE-/- mice. Aa was also observed to induce increased concentrations of serum lipopolysaccharide (LPS) and TNF-α in the mice. The probiotic Lactobacillus rhamnosus GG (GG) and Lactobacillus rhamnosus Lc705 (Lc705) induced the downregulation of several mast cell activation-related genes in cultured human peripheral-derived mast cells. In addition, GG, Lc705, Bifidobacterium animalis ssp. lactis Bb12 (Bb12), and a combination of these three strains with Propionibacter freudenreichii ssp. shermanii JS (PJS) upregulated the expression of Th1 type pro-inflammatory cytokines, including TNF-α and IL-1β, and chemokines CCL-2 and IL-8, as well as the anti-inflammatory cytokine IL-10. The administration of GG and PJS to high fat-fed ApoE*3Leiden mice reduced the number of intestinal mast cells and the concentrations of plasma markers of inflammation, including vascular cell adhesion molecule (VCAM) 1 E-selectin, and serum amyloid A (SAA). In conclusion, Cpn and Aa induced pro-inflammatory actions in cultured mast cells as well as the activation of mast cells and the induction of systemic inflammation markers in vivo. These effects might induce the inflammation in atherosclerotic lesions and, thus, promote the development of atherosclerosis. The probiotic GG and Lc705 suppressed the expression of genes related to mast cell activation and induced the production of Th1 type and anti-inflammatory cytokines. These changes are suggested to alleviate allergic inflammation. In addition, GG and PJS elicited several anti-inflammatory effects in mice with high-fat diet-induced inflammation, including decreases in the numbers of intestinal mast cells and in the concentrations of markers of systemic inflammation. These actions could be beneficial in the prevention or treatment of inflammatory diseases, such as metabolic disorders.
  • Malmivaara-Lämsä, Minna (Finnish Society of Forest Science, Finnish Forest Research Institute, Faculty of Agriculture and Forestry of the University of Helsinki, Faculty of Forestry of the University of Joensuu, 2008)
    The impacts of fragmentation and recreational use on the hemiboreal urban forest understorey vegetation and the microbial community of the humus layer (the phospholipid fatty acid (PLFA) pattern, microbial biomass and microbial activity, measured as basal respiration) were examined in the greater Helsinki area, southern Finland. Trampling tolerance of 1) herb-rich OMT, 2) mesic MT, and 3) sub-xeric VT forests (in decreasing order of fertility) was studied by comparing relative understorey vegetation cover (urban/untrampled reference ratio) of the three forest types. The trampling tolerance of forest vegetation increased with the productivity of the site (sub-xeric < mesic < herb-rich). Wear of understorey vegetation correlated positively with the number of residents (i.e., recreational pressure) around the forest patch. An increase of 15000 residents within a radius of 1 km around a forest patch was associated with ca. 30% decrease in the relative understorey vegetation cover. The cover of dwarf shrub Vaccinium myrtillus in particular decreased with increasing levels of wear. The cover of mosses in urban forests was less than half of that in untrampled reference areas. Cover of tree saplings, mainly Sorbus aucuparia, and some resilient herbs was higher than in the reference areas. In small urban forest fragments, broad-leaved trees, grasses and herbs were more abundant and mosses were scarcer than in larger urban forest areas. Thus, due to trampling and edge effects, resilient herb and grass species are replacing sensitive dwarf shrubs, mosses and lichens in urban forests. Differences in the soil microbial community structure were found between paths and untrampled areas and the effects of paths extended more than one meter from the paths. Paths supported approximately 25-30% higher microbial biomass with a transition zone of at least 1 m from the path edge. However, microbial activity per unit of biomass was lower on paths than in untrampled areas. Furthermore, microbial biomass and activity were 30-45% lower at the first 20 m into the forest fragments, due to low moisture content of humus near the edge. The decreased microbial activity detected at forest edges and paths implies decreased litter decomposition rates, and thus, a change in nutrient cycling. Changes in the decomposition and nutrient supply may in turn affect the diversity and function of plant communities in urban forests. Keywords: boreal forest vegetation, edge effects, phospholipid fatty acids, trampling, urban woodlands, wear
  • Viherä-Aarnio, Anneli (Helsingin yliopisto, 2009)
    The aim of this thesis was to increase our knowledge about the effects of seed origin on the timing of height growth cessation and field performance of silver birch from different latitudes, with special attention paid to the browsing damage by moose in young birch plantations. The effect of seed origin latitude and sowing time on timing of height growth cessation of first-year seedlings was studied in a greenhouse experiment with seven seed origins (lat. 58º - 67ºN). Variation in critical night length (CNL) for 50 % bud set within two latitudinally distant stands (60º and 67ºN) was studied in three phytotron experiments. Browsing by moose on 5-11 -year-old silver birch saplings from latitudinally different seed origins (53º - 67ºN) was studied in a field experiment in southern Finland. Yield and stem quality of 22-year-old silver birch trees of Baltic, Finnish and Russian origin (54º - 63ºN) and the effect of latitudinal seed transfers were studied in two provenance trials at Tuusula, southern and Viitasaari, central Finland. The timing of height growth cessation depended systematically on latitude of seed origin and sowing date. The more northern the seed origin, the earlier the growth cessation and the shorter the growth period. Later sowing dates delayed growth cessation but also shortened the growth period. The mean CNL of the southern ecotype was longer, 6.3 ± 0.2 h (95 % confidence interval), than that of the northern ecotype, 3.1 ± 0.3 h. Within-ecotype variance of the CNL was higher in the northern ecotype (0.484 h2) than in the southern ecotype (0.150 h2). Browsing by moose decreased with increasing latitude of seed origin and sapling height. Origins transferred from more southern latitudes were more heavily browsed than the more northern native ones. Southern Finnish seed origins produced the highest volume per unit area in central Finland (lat. 63º11'N). Estonian and north Latvian stand seed origins, and the southern Finnish plus tree origins, were the most productive ones in southern Finland (lat. 60º21'N). Latitudinal seed transfer distance had a significant effect on survival, stem volume/ha and proportion of trees with a stem defect. The relationship of both survival and stem volume/ha to the latitudinal seed transfer distance was curvilinear. Volume was increased by transferring seed from ca. 2 degrees of latitude from the south. A longer transfer from the south, and transfer from the north, decreased the yield. The proportion of trees with a stem defect increased linearly in relation to the latitudinal seed transfer distance from the south.
  • Vakkuri, Anne (Helsingin yliopisto, 2000)
  • Viskari-Lähdeoja, Suvi (Helsingin yliopisto, 2013)
    Background and aims. Sudden infant death syndrome (SIDS) is a rare lethal event occurring in 0.1 to 0.3 of infants. In Finland, 10 to 20 infants die from SIDS annually. Research has defined many risk factors for SIDS, but the cascade leading to death remains unexplained. Cardiovascular recordings of infants succumbing to SIDS, as well as animal models, suggest that the final sequelae involve cardiovascular collapse resembling hypotensive shock. There is also evidence of previous hypoxia in SIDS infants. In animal studies, vestibulo-mediated cardiovascular control has been shown to be important in hypotensive shock. Hence, we hypothetized that SIDS victims may have impaired vestibulo-mediated cardiovascular control, possibly due to previous hypoxic episodes. In this thesis, we studied cardiovascular control, and especially vestibulo-mediated cardiovascular control in infants with known risk factors for SIDS at 2 to 4 months of age when the risk for SIDS is highest. Study subjects. A full polysomnographic recording with continuous blood pressure (BP) measurement was performed in 50 infants at 2-4 months of age: 20 control infants, nine infants with univentricular heart (UVH) suffering from chronic hypoxia, 10 infants with bronchopulmonary dysplasia (BPD) with intermittent postnatal hypoxic events, and 11 infants whose mothers had smoked during pregnancy, and thus had been exposed to intrauterine hypoxia and nicotine, were studied. In addition, 20 preterm infants were studied at the gestational age of 34-39 weeks to evaluate developmental aspects of cardiovascular control during head-up tilt test and vestibular stimulus. Methods. Linear side motion and 45° head-up tilt tests were performed in quiet non-rapid eye movement sleep (NREM). Heart rate (HR) and BP responses were analysed from the tests without signs of subcortical or cortical arousal. In addition, HR variability during NREM sleep was assessed. As a general marker of cardiovascular reactivity, HR response to spontaneous arousal from NREM sleep was also evaluated. Results.Side motion test. In the side motion test, control infants presented a biphasic response. First, there was a transient increase in HR and BP. This was followed by a decrease in BP to below baseline, and a return to baseline in HR. All other infant groups showed altered responses. UVH infants and preterm infants near term age had markedly reduced responses. Infants with BPD presented with variable responses: some responded similarly to controls, whereas others showed no initial increase in BP, and the following BP decrease was more prominent. Infants with intrauterine exposure to cigarette smoke showed flat initial BP responses, and the following decrease was more prominent, similarly to a subgroup of BPD infants. Tilt test. Control infants presented with a large variability in BP responses to head-up tilting. On average, systolic BP remained, at first, close to baseline, and diastolic BP increased, after which both decreased and remained below baseline even at the end of the tilt test. On average, HR showed a biphasic response with an initial increase followed by a decrease to below and, finally, a return to baseline. UVH infants showed a similar BP response, but their HR response was tachycardic. Preterm infants with BPD presented with an even greater variability in their BP responses to head-up tilts than control infants, but the overall response as a group did not differ from that of the controls. The tilt response of infants exposed to maternal cigarette smoking during pregnancy did not markedly differ from the control response. Preterm infants near term age showed attenuated responses in both cardiovascular measures, together with greater inter-subject variability compared to the control infants. Discussion. In conclusion, the studied infants with SIDS risk factors showed altered vestibulo-mediated cardiovascular control during the linear side motion test and head-up tilt test. The findings support our initial hypothesis that some infants with SIDS risk factors have defective vestibulo-mediated cardiovascular control, which may lead to death in life-threatening situations.
  • Kalliokoski, Annikka (Helsingin yliopisto, 2008)
    Organic anion-transporting polypeptide 1B1 (OATP1B1), encoded by the SLCO1B1 gene, is an influx transporter expressed on the sinusoidal membrane of human hepatocytes. The common c.521T>C (p.Val174Ala) single-nucleotide polymorphism (SNP) of the SLCO1B1 gene has been associated with reduced OATP1B1 transport activity in vitro and increased plasma concentrations of several of its substrate drugs in vivo in humans. Another common SNP of the SLCO1B1 gene, c.388A>G (p.Asn130Asp), defining the SLCO1B1*1B (c.388G-c.521T) haplotype, has been associated with increased OATP1B1 transport activity in vitro. The aim of this thesis was to investigate the role of SLCO1B1 polymorphism in the pharmacokinetics of the oral antidiabetic drugs repaglinide, nateglinide, rosiglitazone, and pioglitazone. Furthermore, the effect of the SLCO1B1 c.521T>C SNP on the extent of interaction between gemfibrozil and repaglinide as well as the role of the SLCO1B1 c.521T>C SNP in the potential interaction between atorvastatin and repaglinide were evaluated. Five crossover studies with 2-4 phases were carried out, with 20-32 healthy volunteers in each study. The effects of the SLCO1B1 c.521T>C SNP on single doses of repaglinide, nateglinide, rosiglitazone, and pioglitazone were investigated in Studies I and V. In Study II, the effects of the c.521T>C SNP on repaglinide pharmacokinetics were investigated in a dose-escalation study, with repaglinide doses ranging from 0.25 to 2 mg. The effects of the SLCO1B1*1B/*1B genotype on repaglinide and nateglinide pharmacokinetics were investigated in Study III. In Study IV, the interactions of gemfibrozil and atorvastatin with repaglinide were evaluated in relation to the c.521T>C SNP. Plasma samples were collected for drug concentration determinations. The pharmacodynamics of repaglinide and nateglinide was assessed by measuring blood glucose concentrations. The mean area under the plasma repaglinide concentration-time curve (AUC) was ~70% larger in SLCO1B1 c.521CC participants than in c.521TT participants (P ≤ 0.001), but no differences existed in the pharmacokinetics of nateglinide, rosiglitazone, and pioglitazone between the two genotype groups. In the dose-escalation study, the AUC of repaglinide was 60-110% (P ≤ 0.001) larger in c.521CC participants than in c.521TT participants after different repaglinide doses. Moreover, the AUC of repaglinide increased linearly with repaglinide dose in both genotype groups (r > 0.88, P 0.001). The AUC of repaglinide was ~30% lower in SLCO1B1*1B/*1B participants than in SLCO1B1*1A/*1A (c.388AA-c.521TT) participants (P = 0.007), but no differences existed in the AUC of nateglinide between the two genotype groups. In the drug-drug interaction study, the mean increase in the repaglinide AUC by gemfibrozil was ~50% (P = 0.002) larger in c.521CC participants than in c.521TT participants, but the relative (7-8-fold) increases in the repaglinide AUC did not differ significantly between the genotype groups. In c.521TT participants, atorvastatin increased repaglinide peak plasma concentration and AUC by ~40% (P = 0.001) and ~20% (P = 0.033), respectively. In each study, after repaglinide administration, there was a tendency towards lower blood glucose concentrations in c.521CC participants than in c.521TT participants. In conclusion, the SLCO1B1 c.521CC genotype is associated with increased and the SLCO1B1*1B/*1B genotype with decreased plasma concentrations of repaglinide, consistent with reduced and enhanced hepatic uptake, respectively. Inhibition of OATP1B1 plays a limited role in the interaction between gemfibrozil and repaglinide. Atorvastatin slightly raises plasma repaglinide concentrations, probably by inhibiting OATP1B1. The findings on the effect of SLCO1B1 polymorphism on the pharmacokinetics of the drugs studied suggest that in vivo in humans OATP1B1 significantly contributes to the hepatic uptake of repaglinide, but not to that of nateglinide, rosiglitazone, or pioglitazone. SLCO1B1 polymorphism may be associated with clinically significant differences in blood glucose-lowering response to repaglinide, but probably has no effect on the response to nateglinide, rosiglitazone, or pioglitazone.
  • Barua, Sepul K (Helsingin yliopisto, 2012)
    This dissertation examines the effects of taxes and policy instruments that aim to regulate climate services from forests. It consists of a summary section and four articles. Articles (I) and (II) examine the effects of taxes on management decisions in the context of managed boreal forests distinguished by forest-owners amenity preferences and also their age. Articles (III) and (IV) examine the role of carbon-based policy instruments in the presence of taxes on land incomes in curbing tropical deforestation. Article (I) reveals that the intensity of forest-owners preferences for forest amenities affects the non-neutrality of forest taxes pertaining to forest harvesting. Therefore, the effects of taxes depend on this intensity. This highlights the importance of developing methods to measure forest-owners amenity preferences quantitatively. Article (II) shows that the age of forest-owners governs their propensity to consume as opposed to leave bequests. Furthermore, it shown that the effects of capital income and inheritance taxes vary across different age-groups of forest-owners. Article (III) demonstrates that taxes on forestry and cash-crop incomes, per se, may be ineffective in curbing tropical forest loss. The carbon payments may complement these taxes, and an effective policy to combat tropical deforestation should jointly target forestry and cash-crop sectors. Article (IV) demonstrates the link between carbon compensation policies and land income taxation. An optimal carbon compensation scheme may require that national governments are allowed to use different compensation rates from that applied globally when passing national level compensations on to the local level. These results suggest that existing policies such as taxation should be accounted for in the analysis and design of international carbon policy instruments that aim at enhancing forests role in climate change mitigation.
  • Aulavuori, Katja (Helsingin yliopisto, 2008)
    Tutkielma käsittelee suomalaisten televisiotekstittäjien ammatillisuutta, käännösprosessia ja digitaalisten tekstitysohjelmien vaikutuksia tekstitysprosessiin ammattitekstittäjien näkökulmasta. Suomen television digitalisoituminen on aiheuttanut mullistuksia myös tekstitysalalla kun tekstitettävä kuvamateriaali on ryhdytty toimittamaan käännöstoimistoille ja tekstittäjille digitaalisena. Teoriaosuudessa käsitellään käännös- ja tekstitystutkimusta sekä koulutusta Suomessa, ammattitaitoa ja ammatillisuutta sekä kääntämisen apukeinoja. Tekstittäminen esitellään erikoistuneena kääntämisen muotona. On kuitenkin myös huomioitava, että kääntäminen on yksi vaihe tekstitysprosessissa. Teoriaosuus päättyy suomalaisten televisiotekstittäjien arjen ja työkentän nykytilanteen käsittelyyn – tekstittäjät työskentelevät monenlaisilla työehdoilla ja laadun kriteerit saatetaan joutua arvioimaan uudelleen. Empiirisen osan alussa esitetään, että suomalaisia televisiotekstittäjiä on haastateltu yllättävän vähän, ja Jääskeläisen ajatuksiin nojaten mainitaan, että tekstittämisen alalla on vielä paljon tutkimatta – etenkin suomalaisesta tekstitysprosessista löytyy tutkittavaa. Tutkimuskohde on ammatikseen televisioon tekstityksiä tekevät kääntäjät. Suomalaiselle tekstitykseen erikoistuneelle käännöstoimistolle työskenteleville tekstittäjille lähetettiin alkutalvesta 2008 kyselylomake, jolla kartoitettiin sekä monivalintakysymyksillä että avoimilla kysymyksillä heidän ammatillisuuttaan, työmenetelmiään, käännös- ja tekstitysprosessiaan, ammattiylpeyttään ja -identiteettiään, ajanhallintaansa, sekä heidän käyttämäänsä digitaalista tekstitysohjelmaa. Tutkimuksessa kävi ilmi, että lähes kolmanneksella vastaajista on ammatistaan neutraali tai jopa negatiivinen käsitys. Näitä tekstittäjiä yhdistää se seikka, että kaikilla on alle 5 vuotta kokemusta alalta. Valtaosa vastanneista on kuitenkin ylpeitä siitä, että toimivat suomen kielen ammattilaisina. Tekstitysprosessi oli lomakkeessa jaettu esikatseluvaiheeseen, käännösvaiheeseen, ajastamisvaiheeseen ja korjauskatseluvaiheeseen. Tekstittäjät pyydettiin mm. arvioimaan tekstitysprosessinsa kokonaiskestoa. Kestoissa ilmeni suuria eroavaisuuksia, joista ainakin osa korreloi kokemuksen kanssa. Runsas puolet vastaajista on hankkinut digitaalisen tekstitysohjelmiston käyttöönsä ja osa ajastaa edelleen käännöstoimistossa muun muassa ohjelmiston kalleuden vuoksi. Digitaalisen ohjelmiston myötä tekstitysprosessiin ja työkäytänteisiin on tullut muutoksia, kun videonauhureista ja televisioista on siirrytty pelkän tietokoneen käyttöön. On mahdollista tehdä etätyötä kaukomailta käsin, kääntää ja ajastaa lomittain tai tehdä esiajastus ja kääntää sitten. Digitaalinen tekniikka on siis mahdollistanut tekstitysprosessin muuttumisen ja vaihtoehtoiset työmenetelmät, mutta kaikista menetelmistä ei välttämättä ole tekstittäjälle hyötyä. Perinteinen tekstitysprosessi (esikatselu, repliikkijakojen merkitseminen käsikirjoitukseen, kääntäminen ja repliikkien laadinta, korjaukset ja tarkastuskatselu) vaikuttaa edelleen tehokkaimmalta. Vaikka työkäytänteet eroavat toisistaan, kokonaiskäsitys on se, että digitalisoitumisen alkukangertelujen jälkeen tekstittäjien työskentely on tehostunut.
  • Pekcan-Hekim, Zeynep (Helsingin yliopisto, 2007)
    In aquatic systems, the ability of both the predator and prey to detect each other may be impaired by turbidity. This could lead to significant changes in the trophic interactions in the food web of lakes. Most fish use their vision for predation and the location of prey can be highly influenced by light level and clarity of the water environment. Turbidity is an optical property of water that causes light to be scattered and absorbed by particles and molecules. Turbidity is highly variable in lakes, due to seasonal changes in suspended sediments, algal blooms and wind-driven suspension of sediments especially in shallow waters. There is evidence that human activity has increased erosion leading to increased turbidity in aquatic systems. Turbidity could also play a significant role in distribution of fish. Turbidity could act as a cover for small fish and reduce predation risk. Diel horizontal migration by fish is common in shallow lakes and is considered as consequences of either optimal foraging behaviour for food or as a trade-off between foraging and predator avoidance. In turbid lakes, diel horizontal migration patterns could differ since turbidity can act as a refuge itself and affect the predator-prey interactions. Laboratory experiments were conducted with perch (Perca fluviatilis L.) and white bream (Abramis björkna (L.)) to clarify the effects of turbidity on their feeding. Additionally to clarify the effects of turbidity on predator preying on different types of prey, pikeperch larvae (Sander lucioperca (L.)), Daphnia pulex (Leydig), Sida crystallina (O.F. Müller), and Chaoborus flavicans (Meigen) were used as prey in different experiments. To clarify the role of turbidity in distribution and diel horizontal migration of perch, roach (Rutilus rutilus (L.)) and white bream, field studies were conducted in shallow turbid lakes. A clear and a turbid shallow lake were compared to investigate distribution of perch and roach in these two lakes in a 15-year study period. Feeding efficiency of perch and white bream was not significantly affected with increasing clay turbidity up to 50 NTU. The perch experiments with pikeperch larvae suggested that clay turbidity could act as a refuge especially at turbidity levels higher than 50 NTU. Perch experiments with different prey types suggested that pikeperch larvae probably use turbidity as a refuge better compared to Daphnia. Increase in turbidity probably has stronger affect on perch predating on plant-attached prey. The main findings of the thesis show that turbidity can play a significant role in distribution of fish. Perch and roach could use turbidity as refuge when macrophytes disappear while small perch may also use high turbidity as refuge when macrophytes are present. Floating-leaved macrophytes are probably good refuges for small fish in clay-turbid lakes and provide a certain level of turbidity and not too complex structure for refuge. The results give light to the predator-prey interactions in turbid environments. Turbidity of water should be taken in to account when studying the diel horizontal migrations and distribution of fish in shallow lakes.
  • Saarinen, Antti (2009)
    Data on the influence of unilateral vocal fold paralysis on breathing, especially other than information obtained by spirometry, are relatively scarce. Even less is known about the effect of its treatment by vocal fold medialization. Consequently, there was a need to study the issue by combining multiple instruments capable of assessing airflow dynamics and voice. This need was emphasized by a recently developed medialization technique, autologous fascia injection; its effects on breathing have not previously been investigated. A cohort of ten patients with unilateral vocal fold paralysis was studied before and after autologous fascia injection by using flow-volume spirometry, body plethysmography and acoustic analysis of breathing and voice. Preoperative results were compared with those of ten healthy controls. A second cohort of 11 subjects with unilateral vocal fold paralysis was studied pre- and postoperatively by using flow-volume spirometry, impulse oscillometry, acoustic analysis of voice, voice handicap index and subjective assessment of dyspnoea. Preoperative peak inspiratory flow and specific airway conductance were significantly lower and airway resistance was significantly higher in the patients than in the healthy controls (78% vs. 107%, 73% vs. 116% and 182% vs. 125% of predicted; p = 0.004, p = 0.004 and p = 0.026, respectively). Patients had a higher root mean square of spectral power of tracheal sounds than controls, and three of them had wheezes as opposed to no wheezing in healthy subjects. Autologous fascia injection significantly improved acoustic parameters of the voice in both cohorts and voice handicap index in the latter cohort, indicating that this procedure successfully improved voice in unilateral vocal fold paralysis. Peak inspiratory flow decreased significantly as a consequence of this procedure (from 4.54 ± 1.68 l to 4.21 ± 1.26 l, p = 0.03, in pooled data of both cohorts), but no change occurred in the other variables of flow-volume spirometry, body-plethysmography and impulse oscillometry. Eight of the ten patients studied by acoustic analysis of breathing had wheezes after vocal fold medialization compared with only three patients before the procedure, and the numbers of wheezes per recorded inspirium and expirium increased significantly (from 0.02 to 0.42 and from 0.03 to 0.36; p = 0.028 and p = 0.043, respectively). In conclusion, unilateral vocal fold paralysis was observed to disturb forced breathing and also to cause some signs of disturbed tidal breathing. Findings of flow volume spirometry were consistent with variable extra-thoracic obstruction. Vocal fold medialization by autologous fascia injection improved the quality of the voice in patients with unilateral vocal fold paralysis, but also decreased peak inspiratory flow and induced wheezing during tidal breathing. However, these airflow changes did not appear to cause significant symptoms in patients.
  • Valtanen, Marjo (Helsingin yliopisto, 2015)
    Urbanization is causing a substantial increase in impervious surfaces and thereby alterations in the hydrological cycle, e.g. by increasing runoff volumes and intensities that can lead to urban flooding. Furthermore, urban runoff is considered as one of the most important surface water pollutant sources. The characteristics of urban runoff are known to vary greatly between land use types and climates. However, in cold climates, only a few studies have tackled urban runoff phenomena and these studies rarely include catchment-based and long-term monitoring on both runoff quantity and quality. Yet, to develop successful urban runoff management practices, knowledge on runoff characteristics from various urban sites that are monitored for several pollutants throughout the year is required. The aim of this thesis was to fill gaps in our knowledge on the effects of urbanization on runoff characteristics and to study the mechanisms affecting runoff generation and pollutant transport during vastly divergent seasons in cold climates. This research was conducted in the city of Lahti, southern Finland, and comprised three urban catchments of varying imperviousness: High catchment (city centre, total impervious area [TIA], 89%), Intermediate catchment (city centre, 62%) and Low catchment (residential, 19%). At each catchment, continuous measurements on runoff flow rate and precipitation were carried out for a period of two years. In addition, runoff samples were taken to determine concentrations for total nitrogen (tot-N), total phosphorus (tot-P), total suspended solids (TSS), total and dissolved heavy metals (Zn, Cu, Cr, Mn, Al, Co, Ni, Pb) and total organic carbon (TOC). I showed that in cold climates, annual runoff volumes, most pollutant loads and some of the pollutant concentrations increased with increasing imperviousness. Furthermore, urbanization altered runoff generation (volume, intensity, duration, number of events) more strongly during the warm than the cold period. However, when the summer was dry and the winter wet, the effects of urbanization on annual runoff volumes diminished most likely due to snow removal. The spring snowmelt period began earlier and occurred as several events at the city centres in comparison to the low-development catchment. In contrast with patterns observed during warm periods, cumulative runoff volumes during cold periods decreased with increasing urbanization when TIA reached about 60%. Nevertheless, urbanization increased both warm and cold period loads for most pollutants. However, the mechanisms controlling runoff event quality were distinct between seasons: during cold periods event loads and concentrations were mainly increased by long event durations, yet, during warm periods the peak intensity of runoff was the main increasing factor whereas concentrations tended to decrease as event durations increased. Because of snow removal in the High catchment with TIA of 89%, snowmelt volumes during spring were not affected by the amount of precipitation. In addition, at the High catchment, warm periods contributed more to annual volumes than cold periods, contrary to the pattern observed at the Low catchment. Irrespective of land use, the largest seasonal pollutant loads and concentrations for several pollutants occurred during spring. However, the importance of the warm season in annual pollutant load generation increased with increasing urbanization. This study provides updated data on pollutant unit loads, especially for city centres and for heavy metals. This thesis - applying a catchment-based approach - also showed, for the first time how the seasonality of runoff volumes and loads change at highly impervious city centres.