Studies on the Effects of Property Taxation, Rent Control and Housing Allowances

Tämä väitöskirja koostuu asuntomarkkinoiden taloustieteellistä analyysia esittelevästä johdantoluvusta ja kolmesta tutkimuksesta, joissa analysoidaan asuntomarkkinoihin vaikuttavia politiikkatoimenpiteitä. Luvussa 2 tutkitaan Suomen kiinteistöverojärjestelmän vaikutusta asuntorakentamiseen. Vuonna 2001 tehtiin uudistus, jonka myötä kunnat voivat verottaa rakentamatonta asuintonttia korkeammalla veroasteella kuin rakennettua tonttia. Maanomistajan rakentamispäätöksen teoreettisen mallin mukaan rakentamattoman tontin korotettu kiinteistöveron pitäisi nopeuttaa rakentamista, mutta toisaalta myös rakentamiseen investoitu rahamäärä saattaa muuttua. Asuintonttien kiinteistöverojen yleinen taso ei vaikuta maanomistajan käyttäytymiseen, sillä tontin verotusarvo ei riipu rakentamispäätöksestä. Vain rakentamattoman ja rakennetun tontin veroasteiden erolla on merkitystä. Empiiriset tulokset ovat sopusoinnussa teorian kanssa. Tulosten mukaan prosenttiyksikön nousu rakentamattoman ja rakennetun tontin veroasteiden erossa lisää omakotialoitusten määrää viidellä prosentilla lyhyellä aikavälillä. Luvussa 3 analysoidaan vuokrasääntelystä vuokralaisille aiheutuvia hyötyjä ja haittoja. Vuokrasäännellyissä asunnoissa asuvat kotitaloudet hyötyvät vuokrasääntelystä alhaisen vuokran muodossa. Heille saattaa kuitenkin koitua myös haittaa siitä, että toiveita vastaavan asunnon löytäminen on vuokrasääntelytilanteessa vaikeaa, koska vapaille asunnoille on suuri määrä ottajia. Vapaarahoitteisen vuokra-asuntokannan vuokrien sääntely purettiin Suomessa asteittain vuosina 1992–1995. Tutkimuksen empiiriset tulokset viittaavat siihen, että vuokrasääntelyn aiheuttamista suurista eroista halutun ja todellisen asuntokulutuksen välillä koituvat hyvinvointitappiot kumosivat merkittävän osan matalien vuokrien hyödyistä vuokralaisille. Luvussa 4 tutkitaan Suomen asumistukijärjestelmän kannustinvaikutuksia. Asumistuen määrää rajoittavat asunnon pinta-alalle ja neliövuokralle asetetut ylärajat. Neliövuokrarajoite voidaan tulkita asumisen laatua rajoittavana tekijänä. Tutkimuksen teoreettisessa osassa osoitetaan, että asumistukijärjestelmä luo vahvat kannustimet muuttaa asuntoihin, joissa pinta-ala- ja laaturajoitteet purevat. Empiiristen tulosten mukaan asumistukeen oikeutetut kotitaloudet eivät näytä reagoivan kannusteisiin. Tukeen oikeutettujen kotitalouksien asumisvalinnat suhteessa pinta-ala ja laaturajoitteisiin vastaavat muiden kotitalouksien valintoja ja asunnonvaihdon mahdollistama potentiaalinen asumistuen lisäys ei nosta muuttotodennäköisyyttä. Muuttamiseen liittyvät kustannukset ja vajavaiset tiedot tukijärjestelmästä saattavat selittää heikkoa reagointia asumistuen luomiin kannustimiin. Toinen mahdollinen selitys on asumistuen vajaakäyttö. Tutkimuksen mukaan vain 70–80 prosenttia asumistukeen oikeutetuista kotitalouksista nostaa tukea. Asumistuen hyödyntämisen todennäköisyys riippuu koulutustasosta, tuen määrästä ja tulo-odotuksista.

Effects of opioids on ventilation and hemodynamics

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.

Biological mechanisms behind clozapine-induced agranulocytosis

Clozapine is the most effective drug in treating therapy-resistant schizophrenia and may even be superior to all other antipsychotics. However, its use is limited by a high incidence (approximately 0.8%) of a severe hematological side effect, agranulocytosis. The exact molecular mechanism(s) of clozapine-induced agranulocytosis is still unknown. We investigated the mechanisms behind responsiveness to clozapine therapy and the risk of developing agranulocytosis by performing an HLA (human leukocyte antigens) association study in patients with schizophrenia. The first group comprised patients defined by responsiveness to first-generation antipsychotics (FGAs) (n= 19). The second group was defined by a lack of response to FGAs but responsiveness to clozapine (n=19). The third group of patients had a history of clozapine-induced granulocytopenia or agranulocytosis (n=26). Finnish healthy blood donors served as controls (n= 120). We found a significantly increased frequency of HLA-A1 among patients who were refractory to FGAs but responsive to clozapine. We also found that the frequency of HLA-A1 was low in patients with clozapine-induced neutropenia or agranulocytosis. These results suggest that HLA-A1 may predict a good therapeutic outcome and a low risk of agranulocytosis and therefore HLA typing may aid in the selection of patients for clozapine therapy. Furthermore, in a subgroup of schizophrenia, HLA-A1 may be in linkage disequilibrium with some vulnerability genes in the MHC (major histocompatibility complex) region on chromosome 6. These genes could be involved in antipsychotic drug response and clozapine-induced agranulocytosis. In addition, we investigated the effect of clozapine on gene expression in granulocytes by performing a microarray analysis on blood leukocytes of 8 schizophrenic patients who had started clozapine therapy for the first time. We identified an altered expression in 4 genes implicated in the maturation or apoptosis of granulocytes: MPO (myeloperoxidase precursor), MNDA (myeloid cell nuclear differentiation antigen), FLT3LG (Fms-related tyrosine kinase 3 ligand) and ITGAL (antigen CD11A, lymphocyte function-associated antigen 1). The altered expression of these genes following clozapine administration may suggest their involvement in clozapine-induced agranulocytosis. Finally, we investigated whether or not normal human bone marrow mesenchymal stromal cells (MSC) are sensitive to clozapine. We treated cultures of human MSCs and human skin fibroblasts with 10 µM of unmodified clozapine and with clozapine bioactivated by oxidation. We found that, independent of bioactivation, clozapine was cytotoxic to MSCs in primary culture, whereas clozapine at the same concentration stimulated the growth of human fibroblasts. This suggests that direct cytotoxicity to MSCs is one possible mechanism by which clozapine induces agranulocytosis.

Combination antiretroviral therapy -associated lipodystrophy : insights into pathogenesis and treatment

Introduction: Combination antiretroviral therapy (cART) has decreased morbidity and mortality of individuals infected with human immunodeficiency virus type 1 (HIV-1). Its use, however, is associated with adverse effects which increase the patients risk of conditions such as diabetes and coronary heart disease. Perhaps the most stigmatizing side effect is lipodystrophy, i.e., the loss of subcutaneous adipose tissue (SAT) in the face, limbs and trunk while fat accumulates intra-abdominally and dorsocervically. The pathogenesis of cART-associated lipodystrophy is obscure. Nucleoside reverse transcriptase inhibitors (NRTI) have been implicated to cause lipoatrophy via mitochondrial toxicity. There is no known effective treatment for cART-associated lipodystrophy during unchanged antiretroviral regimen in humans, but in vitro data have shown uridine to abrogate NRTI-induced toxicity in adipocytes. Aims: To investigate whether i) cART or lipodystrophy associated with its use affect arterial stiffness; ii) lipoatrophic SAT is inflamed compared to non-lipoatrophic SAT; iii) abdominal SAT from patients with compared to those without cART-associated lipoatrophy differs with respect to mitochondrial DNA (mtDNA) content, adipose tissue inflammation and gene expression, and if NRTIs stavudine and zidovudine are associated with different degree of changes; iv) lipoatrophic abdominal SAT differs from preserved dorsocervical SAT with respect to mtDNA content, adipose tissue inflammation and gene expression in patients with cART-associated lipodystrophy and v) whether uridine can revert lipoatrophy and the associated metabolic disturbances in patients on stavudine or zidovudine based cART. Subjects and methods: 64 cART-treated patients with (n=45) and without lipodystrophy/-atrophy (n=19) were compared cross-sectionally. A marker of arterial stiffness, heart rate corrected augmentation index (AgIHR), was measured by pulse wave analysis. Body composition was measured by magnetic resonance imaging and dual-energy X-ray absorptiometry, and liver fat content by proton magnetic resonance spectroscopy. Gene expression and mtDNA content in SAT were assessed by real-time polymerase chain reaction and microarray. Adipose tissue composition and inflammation were assessed by histology and immunohistochemistry. Dorsocervical and abdominal SAT were studied. The efficacy and safety of uridine for the treatment of cART-associated lipoatrophy were evaluated in a randomized, double-blind, placebo-controlled 3-month trial in 20 lipoatrophic cART-treated patients. Results: Duration of antiretroviral treatment and cumulative exposure to NRTIs and protease inhibitors, but not the presence of cART-associated lipodystrophy, predicted AgIHR independent of age and blood pressure. Gene expression of inflammatory markers was increased in SAT of lipodystrophic as compared to non-lipodystrophic patients. Expression of genes involved in adipogenesis, triglyceride synthesis and glucose disposal was lower and of those involved in mitochondrial biogenesis, apoptosis and oxidative stress higher in SAT of patients with than without cART-associated lipoatrophy. Most changes were more pronounced in stavudine-treated than in zidovudine-treated individuals. Lipoatrophic SAT had lower mtDNA than SAT of non-lipoatrophic patients. Expression of inflammatory genes was lower in dorsocervical than in abdominal SAT. Neither depot had characteristics of brown adipose tissue. Despite being spared from lipoatrophy, dorsocervical SAT of lipodystrophic patients had lower mtDNA than the phenotypically similar corresponding depot of non-lipodystrophic patients. The greatest difference in gene expression between dorsocervical and abdominal SAT, irrespective of lipodystrophy status, was in expression of homeobox genes that regulate transcription and regionalization of organs during embryonal development. Uridine increased limb fat and its proportion of total fat, but had no effect on liver fat content and markers of insulin resistance. Conclusions: Long-term cART is associated with increased arterial stiffness and, thus, with higher cardiovascular risk. Lipoatrophic abdominal SAT is characterized by inflammation, apoptosis and mtDNA depletion. As mtDNA is depleted even in non-lipoatrophic dorsocervical SAT, lipoatrophy is unlikely to be caused directly by mtDNA depletion. Preserved dorsocervical SAT of patients with cART-associated lipodystrophy is less inflamed than their lipoatrophic abdominal SAT, and does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal SAT is in expression of transcriptional regulators, homeobox genes, which might explain the differential susceptibility of these adipose tissue depots to cART-induced toxicity. Uridine is able to increase peripheral SAT in lipoatrophic patients during unchanged cART.

Effect of phenolic-rich plant materials on protein and lipid oxidation reactions

The antioxidant activity of natural plant materials rich in phenolic compounds is being widely investigated for protection of food products sensitive to oxidative reactions. In this thesis plant materials rich in phenolic compounds were studied as possible antioxidants to prevent protein and lipid oxidation reactions in different food matrixes such as pork meat patties and corn oil-in water emulsions. Loss of anthocyanins was also measured during oxidation in corn oil-in-water emulsions. In addition, the impact of plant phenolics on amino acid level was studied using tryptophan as a model compound to elucidate their role in preventing the formation of tryptophan oxidation products. A high-performance liquid chromatography (HPLC) method with ultraviolet and fluorescence detection (UV-FL) was developed that enabled fast investigation of formation of tryptophan derived oxidation products. Byproducts of oilseed processes such as rapeseed (Brassica rapa L.), camelina (Camelina sativa) and soy meal (Glycine max L.) as well as Scots pine bark (Pinus sylvestris) and several reference compounds were shown to act as antioxidants toward both protein and lipid oxidation in cooked pork meat patties. In meat, the antioxidant activity of camelina, rapeseed and soy meal were more pronounced when used in combination with a commercial rosemary extract (Rosmarinus officinalis). Berry phenolics such as black currant (Ribes nigrum) anthocyanins and raspberry (Rubus idaeus) ellagitannins showed potent antioxidant activity in corn oil-in-water emulsions toward lipid oxidation with and without β-lactoglobulin. The antioxidant effect was more pronounced in the presence of β-lactoglobulin. The berry phenolics also inhibited the oxidation of tryptophan and cysteine side chains of β-lactoglobulin. The results show that the amino acid side chains were oxidized prior the propagation of lipid oxidation, thereby inhibiting fatty acid scission. In addition, the concentration and color of black currant anthocyanins decreased during the oxidation. Oxidation of tryptophan was investigated in two different oxidation models with hydrogen peroxide (H2O2) and hexanal/FeCl2. Oxidation of tryptophan in both models resulted in oxidation products such as 3a-hydroxypyrroloindole-2-carboxylic acid, dioxindolylalanine, 5-hydroxy-tryptophan, kynurenine, N-formylkynurenine and β-oxindolylalanine. However, formation of tryptamine was only observed in tryptophan oxidized in the presence of H2O2. Pine bark phenolics, black currant anthocyanins, camelina meal phenolics as well as cranberry proanthocyanidins (Vaccinium oxycoccus) provided the best antioxidant effect toward tryptophan and its oxidation products when oxidized with H2O2. The tryptophan modifications formed upon hexanal/FeCl2 treatment were efficiently inhibited by camelina meal followed by rapeseed and soy meal. In contrast, phenolics from raspberry, black currant, and rowanberry (Sorbus aucuparia) acted as weak prooxidants. This thesis contributes to elucidating the effects of natural phenolic compounds as potential antioxidants in order to control and prevent protein and lipid oxidation reactions. Understanding the relationship between phenolic compounds and proteins as well as lipids could lead to the development of new, effective, and multifunctional antioxidant strategies that could be used in food, cosmetic and pharmaceutical applications.

The effect of structure on the dilute solution properties of branched polysaccharides studied with SEC and AsFlFFF

Cereal arabinoxylans, guar galactomannans, and dextrans produced by lactic acid bacteria(LAB) are a structurally diverse group of branched polysaccharides with nutritional and industrial functions. In this thesis, the effect of the chemical structure on the dilute solution properties of these polysaccharides was investigated using size-exclusion chromatography(SEC) and asymmetric flow field-flow fractionation (AsFlFFF) with multiple-detection. The chemical structures of arabinoxylans were determined, whereas galactomannan and dextran structures were studied in previous investigations. Characterization of arabinoxylans revealed differences in the chemical structures of cereal arabinoxylans. Although arabinoxylans from wheat, rye, and barley fiber contained similar amounts of arabinose side units, the substitution pattern of arabinoxylans from different cereals varied. Arabinoxylans from barley husks and commercial low-viscosity wheat arabinoxylan contained a lower number of arabinose side units. Structurally different dextrans were obtained from different LAB. The structural effects on the solution properties could be studied in detail by modifying pure wheat and rye arabinoxylans and guar galactomannan with specific enzymes. The solution characterization of arabinoxylans, enzymatically modified galactomannans, and dextrans revealed the presence of aggregates in aqueous polysaccharide solutions. In the case of arabinoxylans and dextrans, the comparison of molar mass data from aqueous and organic SEC analyses was essential in confirming aggregation, which could not be observed only from the peak or molar mass distribution shapes obtained with aqueous SEC. The AsFlFFF analyses gave further evidence of aggregation. Comparison of molar mass and intrinsic viscosity data of unmodified and partially debranched guar galactomannan, on the other hand, revealed the aggregation of native galactomannan. The arabinoxylan and galactomannan samples with low or enzymatically extensively decreased side unit content behaved similarly in aqueous solution: lower molar mass samples stayed in solution but formed large aggregates, whereas the water solubility of the higher-molar-mass samples decreased significantly. Due to the restricted solubility of galactomannans in organic solvents, only aqueous galactomannan solutions were studied. The SEC and AsFlFFF results differed for the wheat arabinoxylan and dextran samples. Column matrix effects and possible differences in the separation parameters are discussed, and a problem related to the non-established relationship between the separation parameters of the two separation techniques is highlighted. This thesis shows that complementary approaches in the solution characterization of chemically heterogeneous polysaccharides are needed to comprehensively investigate macromolecular behavior in solution. These results may also be valuable when characterizing other branched polysaccharides.