7 resultados para Haematological Parameters

em Helda - Digital Repository of University of Helsinki


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Pressurised hot water extraction (PHWE) exploits the unique temperature-dependent solvent properties of water minimising the use of harmful organic solvents. Water is environmentally friendly, cheap and easily available extraction medium. The effects of temperature, pressure and extraction time in PHWE have often been studied, but here the emphasis was on other parameters important for the extraction, most notably the dimensions of the extraction vessel and the stability and solubility of the analytes to be extracted. Non-linear data analysis and self-organising maps were employed in the data analysis to obtain correlations between the parameters studied, recoveries and relative errors. First, pressurised hot water extraction (PHWE) was combined on-line with liquid chromatography-gas chromatography (LC-GC), and the system was applied to the extraction and analysis of polycyclic aromatic hydrocarbons (PAHs) in sediment. The method is of superior sensitivity compared with the traditional methods, and only a small 10 mg sample was required for analysis. The commercial extraction vessels were replaced by laboratory-made stainless steel vessels because of some problems that arose. The performance of the laboratory-made vessels was comparable to that of the commercial ones. In an investigation of the effect of thermal desorption in PHWE, it was found that at lower temperatures (200C and 250C) the effect of thermal desorption is smaller than the effect of the solvating property of hot water. At 300C, however, thermal desorption is the main mechanism. The effect of the geometry of the extraction vessel on recoveries was studied with five specially constructed extraction vessels. In addition to the extraction vessel geometry, the sediment packing style and the direction of water flow through the vessel were investigated. The geometry of the vessel was found to have only minor effect on the recoveries, and the same was true of the sediment packing style and the direction of water flow through the vessel. These are good results because these parameters do not have to be carefully optimised before the start of extractions. Liquid-liquid extraction (LLE) and solid-phase extraction (SPE) were compared as trapping techniques for PHWE. LLE was more robust than SPE and it provided better recoveries and repeatabilities than did SPE. Problems related to blocking of the Tenax trap and unrepeatable trapping of the analytes were encountered in SPE. Thus, although LLE is more labour intensive, it can be recommended over SPE. The stabilities of the PAHs in aqueous solutions were measured using a batch-type reaction vessel. Degradation was observed at 300C even with the shortest heating time. Ketones and quinones and other oxidation products were observed. Although the conditions of the stability studies differed considerably from the extraction conditions in PHWE, the results indicate that the risk of analyte degradation must be taken into account in PHWE. The aqueous solubilities of acenaphthene, anthracene and pyrene were measured, first below and then above the melting point of the analytes. Measurements below the melting point were made to check that the equipment was working, and the results were compared with those obtained earlier. Good agreement was found between the measured and literature values. A new saturation cell was constructed for the solubility measurements above the melting point of the analytes because the flow-through saturation cell could not be used above the melting point. An exponential relationship was found between the solubilities measured for pyrene and anthracene and temperature.

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Bone mass accrual and maintenance are regulated by a complex interplay between genetic and environmental factors. Recent studies have revealed an important role for the low-density lipoprotein receptor-related protein 5 (LRP5) in this process. The aim of this thesis study was to identify novel variants in the LRP5 gene and to further elucidate the association of LRP5 and its variants with various bone health related clinical characteristics. The results of our studies show that loss-of-function mutations in LRP5 cause severe osteoporosis not only in homozygous subjects but also in the carriers of these mutations, who have significantly reduced bone mineral density (BMD) and increased susceptibility to fractures. In addition, we demonstrated for the first time that a common polymorphic LRP5 variant (p.A1330V) was associated with reduced peak bone mass, an important determinant of BMD and osteoporosis in later life. The results from these two studies are concordant with results seen in other studies on LRP5 mutations and in association studies linking genetic variation in LRP5 with BMD and osteoporosis. Several rare LRP5 variants were identified in children with recurrent fractures. Sequencing and multiplex ligation-dependent probe amplification (MLPA) analyses revealed no disease-causing mutations or whole-exon deletions. Our findings from clinical assessments and family-based genotype-phenotype studies suggested that the rare LRP5 variants identified are not the definite cause of fractures in these children. Clinical assessments of our study subjects with LPR5 mutations revealed an unexpectedly high prevalence of impaired glucose tolerance and dyslipidaemia. Moreover, in subsequent studies we discovered that common polymorphic LRP5 variants are associated with unfavorable metabolic characteristics. Changes in lipid profile were already apparent in pre-pubertal children. These results, together with the findings from other studies, suggest an important role for LRP5 also in glucose and lipid metabolism. Our results underscore the important role of LRP5 not only in bone mass accrual and maintenance of skeletal health but also in glucose and lipid metabolism. The role of LRP5 in bone metabolism has long been studied, but further studies with larger study cohorts are still needed to evaluate the specific role of LRP5 variants as metabolic risk factors.

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Tmn tutkimuksen tavoitteena oli selvitt tilalla mritetyn hyvinvoinnin yhteytt emakoiden tuotantotuloksiin. Hyvinvointia arvioitiin suomalaisen hyvinvointi-indeksin, A-indeksi, avulla. Tuotantotuloksina kytettiin kahta erilaista tuotosaineistoa, jotka molemmat pohjautuivat kansalliseen tuotosseuranta aineistoon. Hyvinvointimritykset tehtiin 30 porsastuotantosikalassa maaliskuun 2007 aikana. A-indeksi koostuu kuudesta kategoriasta liikkumismahdollisuudet, alustan ominaisuudet, sosiaaliset kontaktit, valo, ilma ja melu, ruokinta ja veden saanti sek elinten terveys ja hoidon taso. Jokaisessa kategoriassa on 3-10 posin ympristperist muuttujaa, jotka vaihtelevat osastoittain. Maksimipistemr osastolle on 100. Hyvinvointimittaukset tehtiin porsitus-, tiineytys- ja joutilasosastoilla. Erillisten tiineytysosastojen pienen lukumrn takia (n=7) tilakohtaiset tiineytys- ja joutilasosastopisteet yhdistettiin ja keskiarvoja kytettiin analyyseiss. Yhteyksi tuotokseen tutkittiin kahden eri aineiston avulla 1) Tilaraportti aineisto (n=29) muodostuu muokkaamattomista tila- ja tuotostuloksista tilavierailua edeltvn vuoden ajalta, 2) POTSIaineisto (n=30) muodostuu POTSI-ohjelmalla (MTT) muokatusta tuotantoaineistosta, joka sislt managementtiryhmn (tila, vuosi, vuodenaika) vaikutuksen ensikoiden ja emakoiden pahnuekohtaiseen tuotokseen. Yhteyksi analysointiin korrelaatio- ja regressioanalyysien avulla. Vaikka osallistuminen tutkimukseen oli vapaaehtoista, molempien tuotantoaineistojen perusteella tutkimustilat edustavat keskituottoista suomalaista sikatilaa. A-indeksin kokonaispisteet vaihtelivat vlill 37,564,0 porsitusosastolla ja 39,583,5 joutilasosastolla. Tilaraporttiaineistoa kytettess paremmat pisteet porsitusosaston elinten terveys ja hoidon taso -kategoriasta lyhensivt elinten lisntymissykli, lissivt syntyvien pahnueiden ja porsaiden mr sek alensivat kuolleena syntyneiden lukumr. Regressiomallin mukaan elinten terveys ja hoidon taso -kategoria selitti syntyvien porsaiden lukumrn, porsimisvlin pituuden sek keskiporsimiskerran vaihtelua. Paremmat pisteet joutilasosaston liikkumismahdollisuudet kategoriasta alensivat syntyneiden pahnueiden sek syntyneiden ett vieroitettujen porsaiden lukumr. Regressiomallin mukaan ensikkopahnueiden osuus ja liikkumismahdollisuudet kategorian pisteet selittivt vieroitettujen porsaiden lukumrn vaihtelua. POTSI-aineiston yhteydess kuolleena syntyneiden porsaiden lukumrn aleneminen oli ensikoilla yhteydess parempiin porsitusosaston sosiaalisiin kontakteihin ja emakoilla puolestaan joutilasosaston parempiin elinten terveys ja hoidon taso pisteisiin. Kahden eri tuotantoaineiston avulla saadut tulokset erosivat toisistaan. Seuraavissa tutkimuksissa onkin suositeltavampaa kytt Tilaraporttiaineistoja, joissa tuotokset ilmoitetaan vuosikohtaisina. Tmn tutkimuksen perusteella hyvinvoinnilla ja tuotoksella on yhteyksi, joilla on mys merkittv taloudellista vaikutusta. Erityisesti hyv elinten hoito ja elinten terveys lisvt tuotettujen porsaiden mr ja lyhentvt lisntymiskiertoa. Erityishuomiota tulee kiinnitt vapaana olevien joutilaiden emakoiden sosiaaliseen stressiin ja rehunsaannin varmistamiseen kaikille yksilille.

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Electric activity of the heart consists of repeated cardiomyocyte depolarizations and repolarizations. Abnormalities in repolarization predispose to ventricular arrhythmias. In body surface electrocardiogram, ventricular repolarization generates the T wave. Several electrocardiographic measures have been developed both for clinical and research purposes to detect repolarization abnormalities. The study aim was to investigate modifiers of ventricular repolarization with the focus on the relationship of the left ventricular mass, antihypertensive drugs, and common gene variants, to electrocardiographic repolarization parameters. The prognostic value of repolarization parameters was also assessed. The study subjects originated from a population of more than 200 middle-aged hypertensive men attending the GENRES hypertension study, and from an epidemiological survey, the Health 2000 Study, including more than 6000 participants. Ventricular repolarization was analysed from digital standard 12-lead resting electrocardiograms with two QT-interval based repolarization parameters (QT interval, T-wave peak to T-wave end interval) and with a set of four T-wave morphology parameters. The results showed that in hypertensive men, a linear change in repolarization parameters is present even in the normal range of left ventricular mass, and that even mild left ventricular hypertrophy is associated with potentially adverse electrocardiographic repolarization changes. In addition, treatments with losartan, bisoprolol, amlodipine, and hydrochlorothiazide have divergent short-term effects on repolarization parameters in hypertensive men. Analyses of the general population sample showed that single nucleotide polymorphisms in KCNH2, KCNE1, and NOS1AP genes are associated with changes in QT-interval based repolarization parameters but not consistently with T-wave morphology parameters. T-wave morphology parameters, but not QT interval or T-wave peak to T-wave end interval, provided independent prognostic information on mortality. The prognostic value was specifically related to cardiovascular mortality. The results indicate that, in hypertension, altered ventricular repolarization is already present in mild left ventricular mass increase, and that commonly used antihypertensive drugs may relatively rapidly and treatment-specifically modify electrocardiographic repolarization parameters. Common variants in cardiac ion channel genes and NOS1AP gene may also modify repolarization-related arrhythmia vulnerability. In the general population, T-wave morphology parameters may be useful in the risk assessment of cardiovascular mortality.