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  • Õkva, Kai (Helsingin yliopisto, 2012)
    Discussions on laboratory animal welfare issues often refer to the Three Rs replacement, reduction and refinement. Replacement means substituting living animals with non-sentient systems; reduction refers to using fewer animals and refinement causing less pain, suffering and distress to the animals or improving their welfare. This work is focusing on two R-s: reduction and refinement in mice. If one considers reduction as meaning obtaining trustworthy information from using fewer animals, then this can be achieved by improved research strategies, better experimental design and more sophisticated statistical analyses. One can reduce variation within the group by using isogenic inbred animals or by finding ways to reduce variation in outbred animals. One approach to achieve reduction in outbred animals is to include litter and individual features of the animals, e.g weight dynamics, in the statistical analyses. Since the elevated plus-maze (EPM) test is one of the most common tests to evaluate anxiety-like behaviour, it was used to assess the possible effects of litter and weight on the behaviour of outbred mice and the effects of environmental enrichment (EE) on the behaviour of inbred mice. As a research tool, the effects of acute or chronic administration of ethanol or acute therapy with the nitric oxide synthase (NOS) inhibitor L-NOARG were examined in outbred NIH/S mice. The administration of L-NOARG had no effect on the behaviour of mice after acute or chronic ethanol administration but attenuated the anxiogenic effect of ethanol withdrawal. The litter from which the mice had originated had a significant effect on their behaviour in the EPM test. The behavioural indices of mice, originating from different litters, tended to be above or below the mean of the corresponding drug-treatment group, irrespective of the drug treatment. Litter had a significant effect on the initial weight and also on the weight changes occurring during the adaptation period and ethanol inhalation. An approach to refinement, EE, has been introduced to create more natural species-specific living conditions for laboratory animals. At the same time, it has been claimed that EE can affect the results of behavioural studies and also increase variation. The effects of different types of EE and different time periods were studied in inbred C57BL/6J and BALB/c mice. The exposure of male C57BL/6J mice to the different types of EE objects in the form of cage furniture (CF) -nest box, corner and stairs- induced an anxiolytic-like effect in the EPM test and tended to increase the locomotor activity of mice. This apparent anxiolytic-like effect was most pronounced in the third week. The CF, in the form of modified Tapvei OY mouse stairs, produced an anxiolytic-like effect and increased the locomotor activity in female C57BL/6J mice, but not in BALB/c female mice. In conclusion, the NOS inhibitors may have effects on the behavioural changes caused by ethanol withdrawal. Information about the litter of outbred mice could and should be used in statistical analysis in order to reduce variation and the number of mice needed. In the EPM test, different CF items induced an anxiolytic-like effect in male and female C57BL/6J mice, but not in BALB/c female mice. This effect depended on the type of objects and was influenced by time. This anxiolytic like effect can be interpreted as refinement of the housing by improving animal welfare. The effects of CF should be considered in planning enrichment programs for housing institutions, in designing behavioural experiments and in analyzing the results obtained. Therefore the evaluation of CF could provide the valuable information and it is recommended that CF manufacturers collate and distribute the refinement results on the specific CF items they produce.
  • Nuorteva, Heikki (Finnish Society of Forest Science, 2008)
    A wide range of biotic and abiotic factors, operating over different time perspectives and intensities, cause defoliation and a rapid decrease in the crown size of trees. Scleroderris canker disease [Gremmeniella abietina (Lagerb.) Morelet] has caused widespread crown reduction and tree mortality in Scots pine (Pinus sylvestris L) in forests in Scandinavia during the last three decades. In the 1980's, attempts were made to show, on the basis of the higher foliar N and S concentrations of affected pines in the diseased area, that sulphur and nitrogen deposition predispose trees to G. abietina. Unfortunately, in many studies on defoliated trees, exceptionally high or low needle mineral nutrient concentrations are still often interpreted as one of the causes of tree injury and not, conversely, as the result. In this thesis, three different field experiments, with foliar analysis as the main study method, were conducted in order to asses the possible long-term effects of living crown reduction on the needle nutrient concentrations of Scots pine trees in southern Finland. The crown ratio and length of the living crown were used to estimate the amount of defoliation in the reduced canopies. The material for the partial studies was collected and a total of 968 foliar samples were analysed individually (15-17 elements/sample) on a total of 488 sample trees (140 diseased, 116 pruned and 232 control trees) during the years 1987-1996 in 13 Scots pine stands. All the three experiments of this thesis provided significant evidence that severe, disease-induced defoliation or artificial pruning of the living branches can induce long-lasting nutritional changes in the foliage of the recovering trees under the typical growing conditions for Scots pine. The foliar concentrations of all the 17 mineral nutrients/elements analysed were affected, to a varying degree, by artificial pruning during the following three years. Although Scots pine, as an evergreen conifer, is considered to have low induced chemical responses to defoliation, this study proved experimentally under natural forest conditions that severe artificial pruning or disease-induced defoliation of Scots pine trees may induce biologically significant changes in the concentrations of most of the important macro- and micronutrients, as well as of carbon, in refoliated needles. Concerning the studies in this thesis, I find the results significant in providing new information about the long-term effects of rapid living crown reduction on the foliar nutrient and element status of Scots pine trees. Key words: Foliar analysis, defoliation, needle loss, pruning, nutrients, Pinus sylvestris, Gremmeniella abietina
  • Ekroos, Johan (Helsingin yliopisto, 2010)
    Intensified agricultural practises introduced after the Second World War are identified as a major cause of global biodiversity declines. In several European countries agri-environment support schemes have been introduced to counteract the ongoing biodiversity declines. Farmers participating in agri-environment schemes are financially compensated for decreasing the intensity of farming practises leading to smaller yields and lower income. The Finnish agri-environment support scheme is composed of a set of measures, such as widened field margins along main ditches (obligatory measure), management of features increasing landscape diversity, management of semi-natural grasslands, and organic farming (special agreement measures). The magnitude of the benefits for biodiversity depends on landscape context and the properties of individual schemes. In this thesis I studied whether one agri-environment scheme, organic farming, is beneficial for species diversity and abundance of diurnal lepidopterans, bumblebees, carabid beetles and arable weeds. I found that organic farming did not enhance species richness of selected insect taxa, although bumblebee species richness tended to be higher in organic farms. Abundance of lepidopterans and bumblebees was not enhanced by organic farming, but carabid beetle abundance was higher in mixed farms with both cereal crop production and animal husbandry. Both species richness and abundance of arable weeds were higher in organic farms. My second objective was to study how landscape structure shapes farmland butterfly communities. I found that the percentage of habitat specialists and species with poor dispersal abilities in butterfly assemblages decreased with increasing arable field cover, leading to a dramatic decrease in butterfly beta diversity. In field boundaries local species richness of butterflies was linearly related to landscape species richness in geographic regions with high arable field cover, indicating that butterfly species richness in field boundaries is more limited by landscape factors than local habitat factors. In study landscapes containing semi-natural grasslands the relationship decelerated at high landscape species richness, suggesting that local species richness of butterflies in field boundaries is limited by habitat factors (demanding habitat specialists that occurred in semi-natural grasslands were absent in field margins). My results suggest that management options in field margins will affect mainly generalists, and species with good dispersal abilities, in landscapes with high arable field cover. Habitat specialists and species with poor dispersal abilities may benefit of management options if these are applied in the vicinity of source populations.
  • Heikkilä, Outi (Helsingin yliopisto, 2010)
    The metabolic syndrome and type 1 diabetes are associated with brain alterations such as cognitive decline brain infarctions, atrophy, and white matter lesions. Despite the importance of these alterations, their pathomechanism is still poorly understood. This study was conducted to investigate brain glucose and metabolites in healthy individuals with an increased cardiovascular risk and in patients with type 1 diabetes in order to discover more information on the nature of the known brain alterations. We studied 43 20- to 45-year-old men. Study I compared two groups of non-diabetic men, one with an accumulation of cardiovascular risk factors and another without. Studies II to IV compared men with type 1 diabetes (duration of diabetes 6.7 ± 5.2 years, no microvascular complications) with non-diabetic men. Brain glucose, N-acetylaspartate (NAA), total creatine (tCr), choline, and myo-inositol (mI) were quantified with proton magnetic resonance spectroscopy in three cerebral regions: frontal cortex, frontal white matter, thalamus, and in cerebellar white matter. Data collection was performed for all participants during fasting glycemia and in a subgroup (Studies III and IV), also during a hyperglycemic clamp that increased plasma glucose concentration by 12 mmol/l. In non-diabetic men, the brain glucose concentration correlated linearly with plasma glucose concentration. The cardiovascular risk group (Study I) had a 13% higher plasma glucose concentration than the control group, but no difference in thalamic glucose content. The risk group thus had lower thalamic glucose content than expected. They also had 17% increased tCr (marker of oxidative metabolism). In the control group, tCr correlated with thalamic glucose content, but in the risk group, tCr correlated instead with fasting plasma glucose and 2-h plasma glucose concentration in the oral glucose tolerance test. Risk factors of the metabolic syndrome, most importantly insulin resistance, may thus influence brain metabolism. During fasting glycemia (Study II), regional variation in the cerebral glucose levels appeared in the non-diabetic subjects but not in those with diabetes. In diabetic patients, excess glucose had accumulated predominantly in the white matter where the metabolite alterations were also the most pronounced. Compared to the controls values, the white matter NAA (marker of neuronal metabolism) was 6% lower and mI (glia cell marker) 20% higher. Hyperglycemia is therefore a potent risk factor for diabetic brain disease and the metabolic brain alterations may appear even before any peripheral microvascular complications are detectable. During acute hyperglycemia (Study III), the increase in cerebral glucose content in the patients with type 1 diabetes was, dependent on brain region, between 1.1 and 2.0 mmol/l. An every-day hyperglycemic episode in a diabetic patient may therefore as much as double brain glucose concentration. While chronic hyperglycemia had led to accumulation of glucose in the white matter, acute hyperglycemia burdened predominantly the gray matter. Acute hyperglycemia also revealed that chronic fluctuation in blood glucose may be associated with alterations in glucose uptake or in metabolism in the thalamus. The cerebellar white matter appeared very differently from the cerebral (Study IV). In the non-diabetic men it contained twice as much glucose as the cerebrum. Diabetes had altered neither its glucose content nor the brain metabolites. The cerebellum seems therefore more resistant to the effects of hyperglycemia than is the cerebrum.
  • Rasimus-Sahari, Stiina (Helsingin yliopisto, 2016)
    Humans are exposed to microbes and microbial compounds continuously via environmental exposure and food in addition to our own microbiome. This thesis reports new empirical findings concerning the types of mitochondrial toxins present in food and indoor air and the effects of these toxins on mammalian cells. Dust and aerosolized compounds collected from moisture-damaged buildings were shown to have mitochondriotoxic effects detectable with a boar sperm motility inhibition (BSMI) assay. Toxin-producing bacteria isolated from the dusts and aerosols included producers of the mitochondrial toxins amylosin, cereulide, and valinomycin. In addition, aerosolized valinomycin and toxic chemical compounds emitted from building materials were detected using boar spermatozoa, demonstrating that the BMSI assay could be used to screen for mitochondrial toxicity in indoor air. Amylosin, a mitochondriotoxin produced by Bacillus spp. from indoor air and food, was shown to be immunotoxic: exposure of human primary macrophages to nanomolar concentrations of amylosin stimulated the release of inflammatory cytokines interleukin 1β and interleukin 18. Amylosin is the first bacterial channel-forming ionophore toxin reported to have this effect. Low amounts of amylosin caused significant dose-dependent potassium ion efflux from human somatic cells and boar spermatozoa. Potassium efflux may be the trigger causing the observed cytokine release from macrophages after amylosin exposure. Amylosin also displayed antifungal and antibacterial activity which may give its producers a competitive advantage in mixed microbial communities. Two previously unreported food safety hazards were identified from cereal grains. A novel heat-stable mitochondrial toxin named paenilide, similar to cereulide biochemically and in mode of action, was found to be produced by Paenibacillus tundrae isolated from barley grains. This finding shows that the genus Paenibacillus cannot be considered harmless for human health. Paenilide consisted of two components with molecular masses equal to those of cereulide and homocereulide but with longer chromatographic retention times, indicating more hydrophobic structures than those of the cereulide compounds. Paenilide acted as a lipophilic potassium ionophore, causing depolarization, swelling, uncoupling of oxidative phosphorylation, and loss of respiratory control in isolated rat liver mitochondria. Paenilide accelerated glucose consumption in porcine kidney epithelial cells, causing metabolic acidosis, and was cytotoxic to porcine and murine cells. Paenilide was as toxic as cereulide at nanomolar amounts, making it a possibly potent food poisoning agent. Paenilide was produced at incubation temperatures down to +5°C, indicating potential toxin formation in chilled foods. The second novel finding connected to cereal grains was the discovery of toxin-producing Streptomyces spp. in healthy-looking grains of barley and spring wheat. The barley grain isolates, belonging to the Streptomyces albidoflavus group, produced the mitochondriotoxic macrolide antimycin A, a known disrupter of oxidative phosphorylation. The cause of the mitochondrial toxicity of the spring wheat grain isolates, most closely related to Streptomyces sedi, remained unidentified. The toxicity of the isolates and grains was detected using the BSMI assay, which was sensitive enough to detect nanomolar contamination corresponding to 2 ng of antimycin A per barley grain. Antimycin A was more toxic towards porcine kidney epithelial cells than the mycotoxin enniatin B but less toxic than cereulide or paenilide. Exposure of porcine kidney epithelial cells to these four toxins accelerated glucose consumption and caused mitochondrial depolarization, indicating upregulation of glycolysis. Pancreatic insulin-producing beta cells, however, are not able to switch to glycolytic ATP production and undergo necrotic cell death upon exposure to mitochondrial toxins. Thus, consumption of grains contaminated with mitochondrial toxins may especially affect pancreatic functions. In conlusion, the results of this thesis show that chronic exposure via indoor air or food to sub-lethal concentrations of mitochondriotoxins produced by spore-forming bacteria may be more common than known so far. This exposure may connect to the increasing worldwide incidence of western lifestyle diseases, such as diabetes, asthma, and allergies as well as cardiovascular and neurological disorders. The studied toxins are all heat-stable and produced by spore-formers able to withstand harsh environmental conditions, highlighting that preventing their presence and endurance in food and indoor environments is problematic.
  • 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 (Helsingfors universitet, 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-?), 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.
  • Hohenthal, Michael (2015)
    In most countries there is today more than ever an ongoing discussion about public debt. The purpose of this paper is to highlight the effects of public debt on exercising fiscal policy and the consequences of public debt for the society. As a base this paper first deals with a situation where individuals of one generation live for two periods. A framework for that is developed. This framework is then extended to four multi-period versions. I first extend the framework to one with overlapping generations and inter-generational transfers of wealth. This extension is then modified to take into account transaction costs of the collection of taxes. Next I take into account the distortion effects of the taxation. Then I deal with the pricing of public debt and the final extension describes what is required for a fiscal policy to be considered sustainable. The basic framework shows that with public expenses being kept constant, periodic changes in taxes do not affect the wealth and the consumption of individuals. However, their savings will change in order to balance the variation in taxes. The extension with overlapping-generations implies that if the wealth transfer is positive, changes in public debt will have no effect on the consumption and the net wealth of the individual. If the transfer is zero, there will be an effect, just as in the case with transaction costs connected to the tax collection. It turns out that with distortionary taxation the optimal taxation policy is to keep the periodic tax burden constant. I then show that future budget surpluses are needed to finance public debt and that knowledge of the past affects the present budget surplus and the evaluation of the present public debt. Finally I prove that limiting the public debt to the present value of future increases of the real GNP is a sustainable fiscal path. With perfect capital and labour markets, public debt does not have an impact on the wealth of the society and its individuals. However, in reality the capital and the labour markets are not perfect and there are different transaction costs and negative effects of taxation. Under these circumstances, increased public debt clearly negatively impacts the net wealth. Public debt also creates fiscal requirements on the economic development of the society. The amount of public debt can equal the present value of all future budget surpluses, but cannot exceed the discounted future increases of the real GNP.
  • 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)