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1. Serum, but not monocyte macrophage foam cells derived from low HDL-C subjects, displays reduced cholesterol efflux capacity

Author

Shuhei Nakanishi, Riikka Vikstedt, Sanni Söderlund, Miriam Lee-Rueckert, Anne Hiukka, Christian Ehnholm, Mikko Muilu, Jari Metso, Jussi Naukkarinen, Leena Palotie, Petri T. Kovanen, Matti Jauhiainen, and Marja-Riitta Taskinen

Subjects
atherosclerosis, reverse cholesterol transport, lipoproteins, Biochemistry, QD415-436
Abstract

The main antiatherogenic function of HDL is to promote the efflux of cholesterol from peripheral cells and transport it to the liver for excretion in a process termed reverse cholesterol transport. The aim of this study was to evaluate the cholesterol efflux capacity in low- and high-HDL subjects by utilizing monocytes and serum from 18 low-HDL and 15 high-HDL subjects. Low and high HDL levels were defined, respectively, as HDL ≤10th and HDL ≥90th Finnish age/sex-specific percentile. Cholesterol efflux from [3H]cholesterol-oleate-acetyl-LDL-loaded monocyte-derived macrophages to standard apolipoprotein A-I (apoA-I), HDL2, and serum was measured. In addition, cholesterol efflux from acetyl-LDL-loaded human THP-1 macrophages to individual sera (0.5%) derived from the study subjects was evaluated. Cholesterol efflux to apoA-I, HDL2, and serum from macrophage foam cells derived from low- and high-HDL subjects was similar. The relative ABCA1 and ABCG1 mRNA expression levels in unloaded macrophages, as well as their protein levels in loaded macrophage foam cells, were similar in the two study groups. Cholesterol efflux from THP-1 foam cells to serum recovered from high-HDL subjects was slightly higher than that to serum from low-HDL subjects (P = 0.046). Cholesterol efflux from THP-1 macrophages to serum from study subjects correlated with serum apoB (P = 0.033), apoA-I (P = 0.004), apoA-II (P < 0.0001), and the percentage of apoA-I present in the form of preβ-HDL (P = 0.0001). Our data reveal that macrophages isolated from either low- or high-HDL subjects display similar cholesterol efflux capacity to exogenous acceptors. However, sera from low-HDL subjects have poorer cholesterol acceptor ability as compared with sera from high-HDL subjects.

Published
2009
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2. Common ABCA1 variants, HDL levels, and cellular cholesterol efflux in subjects with familial low HDLs⃞

Author

Aino Soro-Paavonen, Jussi Naukkarinen, Miriam Lee-Rueckert, Hiroshi Watanabe, Elina Rantala, Sanni Soderlund, Anne Hiukka, Petri T. Kovanen, Matti Jauhiainen, Leena Peltonen, and Marja-Riitta Taskinen

Subjects
ATP binding cassette transporter A1, high density lipoprotein, ABCG1, Biochemistry, QD415-436
Abstract

HDL promotes cholesterol efflux from peripheral cells via ABCA1 in the first step of reverse cholesterol transport (RCT). We investigated whether the early steps of RCT were disturbed in subjects with familial low HDL and an increased risk for early atherosclerosis. Cholesterol efflux from monocyte-derived macrophages to lipid-free apolipoprotein A-I (apoA-I; %) was measured in 22 patients with familial low HDL without Tangier disease mutations and in 21 healthy controls. In addition, we defined the different alleles of ABCA1 using single-nucleotide polymorphism haplotypes and measured ABCA1 and ABCG1 mRNA transcript levels in cholesterol-loaded macrophages. Similar ABCA1-mediated cholesterol efflux levels were observed for macrophages derived from control subjects and from low-HDL subjects. However, when efflux of cholesterol was estimated as cholesterol efflux to apoA-I (%)/relative ABCA1 mRNA expression level, cholesterol removal was significantly (P = 0.001) lower in the low-HDL group. Cholesterol-loaded macrophages from low-HDL subjects showed significantly increased levels of ABCA1 mRNA but not of ABCG1 mRNA and were more often carriers of the rare ABCA1 alleles L158 and R219K. These results suggest that defective ABCA1 function in cholesterol-loaded macrophages is one potential contributor to the impaired RCT process and the increased coronary heart disease risk in subjects with familial low HDL.

Published
2007
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5. Korkea rakentaminen kaupunkirakenteessa:tutkielma vaikutusten tunnistamisesta ja suunnittelun ohjaamisesta

Author

Hiukka, H. (Heini)

Abstract

Tiivistelmä. Diplomityöni on tutkielma korkeasta rakentamisesta. Tavoitteenani on ymmärtää korkean rakentamisen suunnitteluperiaatteet ja tutustua tutkielmassa itselleni uuteen typologiaan. Pohdin sitä, millainen vaikutus korkeilla rakennuksilla on kaupunkeihin ja voidaanko tornitaloja suunnittelemalla luoda ihmiselle miellyttävää kaupunkiympäristöä. Tutkielma on laadullinen ja se yhdistelee empiriaa sekä teoriaa monimenetelmällisen metodin puitteissa. Tutkielmassa kartoitan syitä korkean rakentamisen yleistymiselle eri kokoisissa kaupungeissa. Etsin vastausta kysymykseen: Mitä arvoja kaupungit näkevät korkeassa rakentamisessa ja miten he uskovat hyötyvänsä siitä? Tutkin aihetta kaupunkiesimerkkien, karttojen, kaupunkisuunnittelijoiden analyysien ja haastatteluiden sekä omien havaintojeni avulla. Esimerkeissä tuon esille myös arkkitehtien näkemyksiä korkean rakentamisen suunnittelusta. Erityisesti ajatuksia siitä, miten he ovat suunnitelmissaan ratkaisseet kaupunkien asettamat tavoitteet ja vaatimukset. Työssäni inspiroi aiheen ajankohtaisuus. Korkea rakentaminen on 2010-luvun puhutuimpia aiheita niin suunnittelijoiden keskuudessa, kuin yleisessä keskustelussa. Useat kaupungit sekä Suomessa että muissa Pohjoismaissa ovat murrosvaiheessa, jossa kaupunkien kasvuun ja uudistumiseen haetaan ratkaisuja. Korkea rakentaminen nähdään yhtenä mahdollisena ratkaisumenetelmänä, jonka avulla yritetään muun muassa tiivistää keskusta-alueita ja luoda moderneja kaupunkiympäristöjä. Näin ollen useissa kaupungeissa on hyväksytty korkeat rakennukset osaksi niiden uniikkia kaupunkiympäristöään — välillä ilman käsitystä siitä, kuinka tätä typologiaa tulisi ohjeistaa, rajoittaa tai hyödyntää. Löytääkseni tavan suunnitella korkeita rakennuksia käyn läpi toimintoihin ja havainnointiin perustuvia suunnitteluanalyyseja ja kokoan suunnitteluohjeita kolmen kaupungin korkean rakentamisen ohjeistuksista. Toronto, Haag ja Espoo ovat kaupunkeina erilaisia, mutta pohjaavat ohjeistuksensa samaan ideaan eli korkean rakennuksen kolmijakoon: jalustaan, runkoon ja huippuun. Jakamalla rakennus pienempiin osiin suunnittelussa voidaan keskittyä tarkemmin kunkin osan ominaisuuksiin, vaikutuksiin ja toteutukseen. Tavoitteenani on löytää suunnittelun keinoja, joilla korkea rakentaminen voidaan yhdistää ympäröivään kaupunkirakenteeseen ja lisätä vuorovaikutusta rakennusta ympäröivän kaupunkitilan kanssa. Suunnittelun avulla korkea rakennus voidaan tuoda lähemmäs ihmisen mittakaavaa ja luoda niiden avulla käyttäjäystävällisempää ympäristöä.Building tall in the urban fabric : recognizing the impacts and design guidance. Abstract. In my master’s thesis I will investigate a topic that is very current right now: tall buildings. I will familiarize myself with new architecture typology and the goal is to understand the designing principles of tall building architecture. I will study how tall buildings affect the cityscape and urban fabric, and how high-rise buildings can be used to design human friendly environments. My research method is qualitative combined with empirical aspects and theory using mixed method study. My aim is to find reasons to why tall buildings have become more and more common in cities of many different sizes. Doing so I will attempt to answer to the following question: What values do cities see in building upwards and how do cities believe they will benefit from it? I contemplate these themes using examples of different cities, maps, analyses made by urbanists, interviews and via my own observations. In these examples, I have also attempted to bring forward the vision of different architects regarding tall building design. I am especially interested in how architects have approached the aims and restrictions that cities have set to their building projects. The main inspiration for my thesis is the topicality of the subject. Tall buildings are one of the most debated topics in the 2010s among both professionals and in general discussion. Many cities in Finland and in other Nordic countries are in transition: As cities grow, they try to find new solutions to execute urban areas. Building tall is seen as one solution in building more compact urban structure and creating modern urban spaces. These cities have started to apply tall building typology to their unique cityscapes. Sometimes without understanding how this typology should be designed, restricted and used for the cities’ benefit. To find a way to design tall buildings, I investigate different design methods which are based on how people perceive their environment and behave in urban spaces. I go through the design guidance from three different cities: Toronto, Haag and Espoo. The cities are all different, but the instructions are based on the same idea, which is to divide tall building into three different parts: the base, the shaft and the tower top. When tall buildings are designed in smaller parts, designers can focus on features, impacts and execution more precisely. My goal is to find ways to connect tall building design to its surroundings and strengthen the interaction between building and the surrounding city scape. With architectural elements tall buildings can be brought closer to human scale and be used to create more human friendly environments.

Published
2020

7. High density lipoprotein structural changes and drug response in lipidomic profiles following the long-term fenofibrate therapy in the FIELD substudy.

Author

Laxman Yetukuri, Ilkka Huopaniemi, Artturi Koivuniemi, Marianna Maranghi, Anne Hiukka, Heli Nygren, Samuel Kaski, Marja-Riitta Taskinen, Ilpo Vattulainen, Matti Jauhiainen, and Matej Orešič

Subjects
Medicine, Science
Abstract

In a recent FIELD study the fenofibrate therapy surprisingly failed to achieve significant benefit over placebo in the primary endpoint of coronary heart disease events. Increased levels of atherogenic homocysteine were observed in some patients assigned to fenofibrate therapy but the molecular mechanisms behind this are poorly understood. Herein we investigated HDL lipidomic profiles associated with fenofibrate treatment and the drug-induced Hcy levels in the FIELD substudy. We found that fenofibrate leads to complex HDL compositional changes including increased apoA-II, diminishment of lysophosphatidylcholines and increase of sphingomyelins. Ethanolamine plasmalogens were diminished only in a subgroup of fenofibrate-treated patients with elevated homocysteine levels. Finally we performed molecular dynamics simulations to qualitatively reconstitute HDL particles in silico. We found that increased number of apoA-II excludes neutral lipids from HDL surface and apoA-II is more deeply buried in the lipid matrix than apoA-I. In conclusion, a detailed molecular characterization of HDL may provide surrogates for predictors of drug response and thus help identify the patients who might benefit from fenofibrate treatment.

Published
2011
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15. Susceptibility of defoliated Scots pine to spontaneous and induced attack by Tomicus piniperda and Tomicus minor

Author

Annila, Erkki, Långström, Bo, Varama, Martti, Hiukka, Risto, and Niemelä, Pekka

Subjects
Forestry, SD1-669.5
Abstract

In 1990â1991, Diprion pini extensively defoliated Scots pine (Pinus sylvestris L.) trees in Lauhanvuori National Park in southwestern Finland. Many trees lost all their foliage, while others had ca. 10% foliage left after the second year of defoliation. Outside the national park, many nearby stands were also heavily defoliated in 1990, but were sprayed with diflubenzuron (Dimilin®) in 1991. This protected the current year needles, corresponding to ca 30% of full foliage. In spring 1992, pine trees with 0, 10, 30 and 100% foliage remaining (10 small and 10 large trees in each category) were baited with pine bolts to induce stem attacks by pine shoot beetles. All baited trees were attacked by Tomicus piniperda and some by T. minor. The attacks failed in all these trees except those that were totally defoliated and some of the small trees with 10% foliage left. Many unbaited trees escaped attack entirely, but only totally defoliated trees were successfully colonized (i.e. produced brood). Attack densities and brood production figures peaked in baited, large and totally defoliated trees. None of the measures (cambial electrical resistance, resin flow, induced lesion length by fungal inoculation, amount of hydrocarbons or phenolic compounds) used to describe tree vigour at the time of attack gave better information than the estimated remaining foliage. We conclude that the risk for beetle-induced mortality following defoliation is a function of remaining needle biomass and beetle pressure. Even at high beetle densities (as was simulated by baiting of trees), trees with 10% of the foliage remaining were able to defend themselves against attacking pine shoot beetles.

Published
1999
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18. Serum, but not monocyte macrophage foam cells derived from low HDL-C subjects, displays reduced cholesterol efflux capacity

Author

Miriam Lee-Rueckert, Matti Jauhiainen, Jari Metso, Marja-Riitta Taskinen, Christian Ehnholm, Mikko Muilu, Riikka Vikstedt, Shuhei Nakanishi, Sanni Söderlund, Petri T. Kovanen, Anne Hiukka, Jussi Naukkarinen, and Leena Palotie

Subjects
Adult, Male, medicine.medical_specialty, Apolipoprotein B, QD415-436, 030204 cardiovascular system & hematology, Biochemistry, Monocytes, Excretion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Macrophage, Humans, RNA, Messenger, Cells, Cultured, 030304 developmental biology, ATP Binding Cassette Transporter, Subfamily G, Member 1, 0303 health sciences, biology, Chemistry, Cholesterol, Macrophages, Reverse cholesterol transport, Cholesterol, HDL, nutritional and metabolic diseases, Cell Biology, Middle Aged, reverse cholesterol transport, lipoproteins, ATP Binding Cassette Transporter 1, ABCA1, Immunology, biology.protein, ATP-Binding Cassette Transporters, Female, lipids (amino acids, peptides, and proteins), Efflux, atherosclerosis, Foam Cells
Abstract

The main antiatherogenic function of HDL is to promote the efflux of cholesterol from peripheral cells and transport it to the liver for excretion in a process termed reverse cholesterol transport. The aim of this study was to evaluate the cholesterol efflux capacity in low- and high-HDL subjects by utilizing monocytes and serum from 18 low-HDL and 15 high-HDL subjects. Low and high HDL levels were defined, respectively, as HDLor =10(th) and HDLor =90(th) Finnish age/sex-specific percentile. Cholesterol efflux from [(3)H]cholesterol-oleate-acetyl-LDL-loaded monocyte-derived macrophages to standard apolipoprotein A-I (apoA-I), HDL(2), and serum was measured. In addition, cholesterol efflux from acetyl-LDL-loaded human THP-1 macrophages to individual sera (0.5%) derived from the study subjects was evaluated. Cholesterol efflux to apoA-I, HDL(2), and serum from macrophage foam cells derived from low- and high-HDL subjects was similar. The relative ABCA1 and ABCG1 mRNA expression levels in unloaded macrophages, as well as their protein levels in loaded macrophage foam cells, were similar in the two study groups. Cholesterol efflux from THP-1 foam cells to serum recovered from high-HDL subjects was slightly higher than that to serum from low-HDL subjects (P = 0.046). Cholesterol efflux from THP-1 macrophages to serum from study subjects correlated with serum apoB (P = 0.033), apoA-I (P = 0.004), apoA-II (P0.0001), and the percentage of apoA-I present in the form of prebeta-HDL (P = 0.0001). Our data reveal that macrophages isolated from either low- or high-HDL subjects display similar cholesterol efflux capacity to exogenous acceptors. However, sera from low-HDL subjects have poorer cholesterol acceptor ability as compared with sera from high-HDL subjects.

Published
2009

19. ApoCIII-Enriched LDL in Type 2 Diabetes Displays Altered Lipid Composition, Increased Susceptibility for Sphingomyelinase, and Increased Binding to Biglycan

Author

Jan Borén, Kim Ekroos, Marcus Ståhlman, Sven-Olof Olofsson, Susanne Teneberg, Olov Wiklund, Lillemor Mattsson Hultén, Malin Levin, Anne Hiukka, Martin Adiels, E. Leinonen, C. Pettersson, Matej Orešič, and Marja-Riitta Taskinen

Subjects
Male, Apolipoprotein B, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Sphingomyelin phosphodiesterase, Mice, 0302 clinical medicine, Risk Factors, Biglycan, Cells, Cultured, Hypertriglyceridemia, 0303 health sciences, Extracellular Matrix Proteins, biology, Chemistry, Hydrolysis, Middle Aged, 3. Good health, Lipoproteins, LDL, Sphingomyelin Phosphodiesterase, Female, Proteoglycans, Original Article, lipids (amino acids, peptides, and proteins), Sphingomyelin, medicine.medical_specialty, Mice, Transgenic, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Internal Medicine, medicine, Animals, Humans, 030304 developmental biology, Aged, Apolipoproteins B, Apolipoprotein C-III, Proteoglycan binding, Endothelial Cells, medicine.disease, Endocrinology, Metabolism, Diabetes Mellitus, Type 2, biology.protein
Abstract

OBJECTIVE Apolipoprotein CIII (apoCIII) is an independent risk factor for cardiovascular disease, but the molecular mechanisms involved are poorly understood. We investigated potential proatherogenic properties of apoCIII-containing LDL from hypertriglyceridemic patients with type 2 diabetes. RESEARCH DESIGN AND METHODS LDL was isolated from control subjects, subjects with type 2 diabetes, and apoB transgenic mice. LDL-biglycan binding was analyzed with a solid-phase assay using immunoplates coated with biglycan. Lipid composition was analyzed with mass spectrometry. Hydrolysis of LDL by sphingomyelinase was analyzed after labeling plasma LDL with [3H]sphingomyelin. ApoCIII isoforms were quantified after isoelectric focusing. Human aortic endothelial cells were incubated with desialylated apoCIII or with LDL enriched with specific apoCIII isoforms. RESULTS We showed that enriching LDL with apoCIII only induced a small increase in LDL-proteoglycan binding, and this effect was dependent on a functional site A in apoB100. Our findings indicated that intrinsic characteristics of the diabetic LDL other than apoCIII are responsible for further increased proteoglycan binding of diabetic LDL with high-endogenous apoCIII, and we showed alterations in the lipid composition of diabetic LDL with high apoCIII. We also demonstrated that high apoCIII increased susceptibility of LDL to hydrolysis and aggregation by sphingomyelinases. In addition, we demonstrated that sialylation of apoCIII increased with increasing apoCIII content and that sialylation of apoCIII was essential for its proinflammatory properties. CONCLUSIONS We have demonstrated a number of features of apoCIII-containing LDL from hypertriglyceridemic patients with type 2 diabetes that could explain the proatherogenic role of apoCIII.

Published
2009
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20. Common ABCA1 variants, HDL levels, and cellular cholesterol efflux in subjects with familial low HDLs⃞

Author

Leena Peltonen, Sanni Söderlund, Elina Rantala, Jussi Naukkarinen, Aino Soro-Paavonen, Matti Jauhiainen, Miriam Lee-Rueckert, Petri T. Kovanen, Anne Hiukka, Hiroshi Watanabe, and Marja-Riitta Taskinen

Subjects
Male, Apolipoprotein B, 030204 cardiovascular system & hematology, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, High-density lipoprotein, Tangier disease, Gene Frequency, polycyclic compounds, Cells, Cultured, 0303 health sciences, biology, Reverse Transcriptase Polymerase Chain Reaction, Reverse cholesterol transport, Middle Aged, Hypolipoproteinemias, Cholesterol, ABCG1, high density lipoprotein, Female, lipids (amino acids, peptides, and proteins), Efflux, Lipoproteins, HDL, ATP Binding Cassette Transporter 1, medicine.medical_specialty, QD415-436, 03 medical and health sciences, Internal medicine, medicine, Humans, RNA, Messenger, 030304 developmental biology, Polymorphism, Genetic, Apolipoprotein A-I, Macrophages, nutritional and metabolic diseases, Cell Biology, medicine.disease, chemistry, ABCA1, Multivariate Analysis, biology.protein, ATP-Binding Cassette Transporters, ATP binding cassette transporter A1
Abstract

HDL promotes cholesterol efflux from peripheral cells via ABCA1 in the first step of reverse cholesterol transport (RCT). We investigated whether the early steps of RCT were disturbed in subjects with familial low HDL and an increased risk for early atherosclerosis. Cholesterol efflux from monocyte-derived macrophages to lipid-free apolipoprotein A-I (apoA-I; %) was measured in 22 patients with familial low HDL without Tangier disease mutations and in 21 healthy controls. In addition, we defined the different alleles of ABCA1 using single-nucleotide polymorphism haplotypes and measured ABCA1 and ABCG1 mRNA transcript levels in cholesterol-loaded macrophages. Similar ABCA1-mediated cholesterol efflux levels were observed for macrophages derived from control subjects and from low-HDL subjects. However, when efflux of cholesterol was estimated as cholesterol efflux to apoA-I (%)/relative ABCA1 mRNA expression level, cholesterol removal was significantly (P = 0.001) lower in the low-HDL group. Cholesterol-loaded macrophages from low-HDL subjects showed significantly increased levels of ABCA1 mRNA but not of ABCG1 mRNA and were more often carriers of the rare ABCA1 alleles L158 and R219K. These results suggest that defective ABCA1 function in cholesterol-loaded macrophages is one potential contributor to the impaired RCT process and the increased coronary heart disease risk in subjects with familial low HDL.

Published
2007

21. Decreased High-Density Lipoprotein (HDL) Particle Size, Preβ-, and Large HDL Subspecies Concentration in Finnish Low-HDL Families

Author

E. Leinonen, Sanni Söderlund, Matti Jauhiainen, Tomi-Pekka Tuomainen, Anne Hiukka, C. Alagona, Hiroshi Watanabe, Riitta Salonen, Aino Soro-Paavonen, Marja-Riitta Taskinen, and Christian Ehnholm

Subjects
Adult, Male, medicine.medical_specialty, Coronary Disease, Subspecies, HDL Particle Size, Body Mass Index, chemistry.chemical_compound, Sex Factors, High-density lipoprotein, Risk Factors, Internal medicine, Humans, Medicine, Particle Size, Finland, business.industry, Cholesterol, Cholesterol, HDL, Age Factors, Middle Aged, Carotid Arteries, Blood pressure, Endocrinology, chemistry, Intima-media thickness, Regression Analysis, Female, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, business, Body mass index, Lipoprotein
Abstract

Objective— High-density lipoprotein (HDL) cholesterol correlates inversely with the risk of coronary heart disease (CHD). The precise antiatherogenic mechanisms of HDL subspecies are not thoroughly elucidated. We studied the relationship between carotid intima-media thickness (IMT) and HDL subspecies distribution in Finnish families with low HDL cholesterol and premature CHD. Methods and Results— Altogether, 148 members of Finnish low-HDL families and 133 healthy control subjects participated in our study. HDL particle size was significantly smaller in affected family members (HDL ≤10th Finnish age-sex specific percentile) compared with unaffected family members and control subjects (9.1±0.04 nm versus 9.5±0.05 nm, P P 2b particles as well as preβ-HDL concentration were significantly decreased among the affected family members. Mean IMT was significantly higher in the affected family members than in the control subjects (0.85±0.01 mm versus 0.79±0.01 mm; P 2b , systolic blood pressure, and preβ-HDL were significant independent determinants of mean IMT. Conclusions— The decreased levels of HDL 2b and preβ-HDL reflect the potentially efflux-deficient HDL subspecies profile in the affected low-HDL family members. Decreased HDL particle size caused by the decrease of plasma concentration of HDL 2b and decreased preβ-HDL levels correlate with increased IMT.

Published
2006
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22. Increased augmentation of central blood pressure is associated with increases in carotid intima–media thickness in type 2 diabetic patients

Author

Riitta Salonen, Jukka T. Salonen, E. Leinonen, Anne Hiukka, Jukka Westerbacka, Hannele Yki-Järvinen, and Marja-Riitta Taskinen

Subjects
Male, Aging, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Diastole, Hemodynamics, Blood Pressure, Type 2 diabetes, Body Mass Index, Risk Factors, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Aged, Ultrasonography, Waist-Hip Ratio, business.industry, Body Weight, Middle Aged, medicine.disease, Carotid Arteries, Blood pressure, medicine.anatomical_structure, Endocrinology, Diabetes Mellitus, Type 2, Intima-media thickness, cardiovascular system, Cardiology, Arterial stiffness, Female, Tunica Intima, business, Artery
Abstract

Type 2 diabetes is associated with a two- to seven-fold increase in cardiovascular morbidity and mortality. The aim of this study was to determine the relationships between intima–media thickness (IMT), an established marker of atherosclerosis, large artery function and other determinants of cardiovascular risk in type 2 diabetic patients. We studied 228 type 2 diabetic patients (75 women, aged 62±2 years [mean±SEM]). Carotid IMT was bilaterally measured using ultrasound technology. Applanation tonometry and pulse wave analysis were used to measure aortic systolic and diastolic blood pressures, central pressure augmentation (AG) and the augmentation index (AIx), a measure of systemic arterial stiffness. Conventional cardiovascular risk factors (lipids, HbA1c, smoking and diabetes duration) were also assessed. Women had higher AG and AIx (p

Published
2005
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23. Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes

Author

E. Leinonen, H. Hilden, Anne Hiukka, Marja-Riitta Taskinen, Jamila Fruchart-Najib, and Jean-Charles Fruchart

Subjects
Male, Apolipoprotein E, medicine.medical_specialty, Very low-density lipoprotein, Apolipoprotein B, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Lipoproteins, VLDL, Body Mass Index, chemistry.chemical_compound, Fenofibrate, Reference Values, Internal medicine, Internal Medicine, medicine, Humans, Apolipoproteins C, Triglycerides, Aged, Hypolipidemic Agents, Radial immunodiffusion, Intermediate-density lipoprotein, Apolipoprotein C-III, Triglyceride, biology, Middle Aged, medicine.disease, Lipids, Endocrinology, Diabetes Mellitus, Type 2, chemistry, biology.protein, Female, lipids (amino acids, peptides, and proteins), Lipoprotein
Abstract

Very low density lipoprotein (VLDL) particles are heterogeneous, comprising two main subspecies, VLDL 1 (Sf 60-400) and VLDL 2 (Sf 20-60). The aim of the study was to examine the distribution and composition of VLDL subspecies in type 2 diabetes. We studied the composition and concentration of triglyceride-rich lipoproteins (TRLs) in 217 type 2 diabetic patients and 93 control subjects between 50 and 75 years of age. Lipoprotein subspecies were separated by density-gradient ultracentrifugation. Apolipoprotein (apo) CIII and apo E in plasma and apo CIII in TRL subspecies were measured by nephelometry and apo CII in serum by a commercial kit using a single radial immunodiffusion method. The concentrations of VLDL 1, VLDL 2 and intermediate density lipoprotein were significantly increased in type 2 diabetes subjects, the change being most marked for VLDL 1. There was a strong linear correlation between VLDL 1 triglycerides and plasma triglycerides in both groups (r=0.879, p

Published
2005
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24. Low-grade inflammation, endothelial activation and carotid intima-media thickness in type 2 diabetes

Author

Eva Hurt-Camejo, Jukka T. Salonen, S. S. Sarna, Riitta Salonen, Jukka Westerbacka, E. Leinonen, L. Mattson Hultén, Olov Wiklund, Marja-Riitta Taskinen, and Anne Hiukka

Subjects
Male, medicine.medical_specialty, Endothelium, Vascular Cell Adhesion Molecule-1, Inflammation, Type 2 diabetes, 030204 cardiovascular system & hematology, Endothelial activation, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, cardiovascular diseases, Serum amyloid A, Aged, Ultrasonography, 030304 developmental biology, Serum Amyloid A Protein, 0303 health sciences, Interleukin-6, business.industry, Age Factors, Middle Aged, Intercellular Adhesion Molecule-1, medicine.disease, 3. Good health, C-Reactive Protein, Carotid Arteries, Cross-Sectional Studies, Endocrinology, medicine.anatomical_structure, Diabetes Mellitus, Type 2, Intima-media thickness, Case-Control Studies, Hypertension, Linear Models, Female, Endothelium, Vascular, Metabolic syndrome, medicine.symptom, E-Selectin, Tunica Intima, business, Biomarkers, Diabetic Angiopathies
Abstract

Objectives. The objective of this study was to assess the relationship between inflammation, endothelial activation and incipient atherosclerosis in type 2 diabetes. Design. Cross-sectional study. Setting and subjects. We studied 239 type 2 diabetic patients [71 with clinical cardiovascular disease (CVD)] and 78 healthy control subjects, aged 50–75 in a single research centre. Methods. Carotid intima-media thickness (IMT) was determined by ultrasound. Circulating intracellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, ultra-sensitive C-reactive protein, human serum amyloid A, interleukin-6, monocyte colony-stimulating factor, secretory nonpancreatic phospholipase A2 type IIA, glucose, HbA1c, and lipid/lipoprotein variables were measured. Results. Carotid IMT was significantly thicker in diabetic patients than healthy controls across the whole age range. IMT was also thicker in diabetic patients with, than without, CVD, but this difference disappeared after controlling for confounding factors. Concentrations of the inflammatory and endothelial markers except IL-6 were significantly higher in the diabetic patients than in healthy controls, but comparable in diabetic patients with and without CVD. The main determinants of IMT in the diabetic patients were blood pressure, age and diabetes duration. Conclusions. Low-grade inflammation and endothelial activation are increased in diabetic patients but do not associate with IMT or clinical CVD. The inflammatory reaction seems to be rather a feature of the metabolic syndrome than a direct determinant of atherosclerosis.

Published
2004
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25. 5.-9.-luokkalaisten tyttöjen ja poikien väliset erot tavoiteorientaatiossa ja kykyuskomuksissa ja niiden trendit

Author

Hiukka, Pirta

Subjects
minäsuuntautuneisuus, motivaatio, tehtäväsuuntautuneisuus, tavoiteorientaatio, nuoret, koululiikunta, odotusarvoteoria, kykyuskomukset
Abstract

Pirta Hiukka (2014). 5.-9. luokkalaisten tyttöjen ja poikien väliset erot tavoiteorientaatiossa ja kykyuskomuksissa ja niiden trendit. Liikuntakasvatuksen laitos, Jyväskylän yliopisto, liikuntapedagogiikan pro gradu-tutkielma, 65 s., 3 liitettä. Tutkimuksen tavoitteena oli arvioida 5-9-luokkalaisten nuorten motivaatiokäyttäytymistä liikuntatunneilla ja erityisesti sitä, miten tytöt ja pojat eroavat toisistaan itsearvioitujen tehtäväsuuntautuneisuutensa, minäsuuntautuneisuutensa ja kykyuskomustensa suhteen. Eroavaisuuksia näiden muuttujien arvoissa tarkasteltiin myös eri luokka-asteiden välillä yleisesti kaikki oppilaat huomioiden sekä molempien sukupuolten kohdalla erikseen. Tutkimuksen tarkoituksena oli myös selvittää, miten vuoden 2010 ja 2011 tehtävä- ja minäsuuntautuneisuus sekä vuoden 2011 kykyuskomukset kytkeytyvät toisiinsa molemmilla sukupuolilla. Lisäksi yhtenä päämääränä oli saada tietoa siitä, että tapahtuiko tehtävä- ja minäsuuntautuneisuudessa muutoksia vuosien 2010 ja 2011 välillä tytöillä ja pojilla ja että onko sukupuoli yhteydessä mahdollisesti ilmeneviin muutoksiin. Tutkimuksen kohdejoukkona olivat kaikki Sotkamon peruskoulut, joista 11 olivat alakouluja ja yksi yläkoulu. Tutkimuksen tarkoituksena oli kerätä tietoja samoilta oppilailta vuoden välein, niin että vuoden 2010 tutkimuksen kohdejoukko koostui 5-8-luokkalaisista oppilaista ja vuoden 2011 6-9-luokkalaisista. Vuonna 2010 tutkimukseen osallistui yhteensä 525 oppilasta (257 tyttöä, 228 poikaa) ja vuonna 2011 puolestaan 566 (299 tyttöä, 267 poikaa) oppilasta. Tutkielmani lopullisen otoksen muodostivat lopulta ne oppilaat, jotka ottivat tutkimukseen tunnistettavasti osaa molempina vuosina (n = 182; 102 tyttöä, 80 poikaa). Tavoiteorientaation mittaukseen käytettiin Perception of Success Questionnaire- mittarin (Roberts ym. 1998) suomenkielistä versiota (Liukkonen 1998). Kykyuskomuksia tutkittiin Ecclesin ym. (1983) odotusarvoteorian pohjalta kehitetyllä suomenkielisellä mittarilla (Ylipiipari 2011). Itsearvioiden luotettavuutta tarkasteltiin Cronbachin alfakertoimilla, jotka vaihtelivat .86 ja .94 välillä. Tuloksia analysoitiin riippumattomien ja riippuvien otosten t-testien, yhdensuuntaisen varianssianalyysin, Pearsonin tulomomenttikorrelaation ja toistettujen mittausten MANOVA-testin avulla. Tehtäväsuuntautuneisuudessa ei löytynyt eroa sukupuolten välillä, mutta sen sijaan tytöt olivat selvästi poikia minäsuuntautuneempia molempina vuosina. Erityisesti vuonna 2011 9-luokkalaiset tytöt olivat merkittävästi samanikäisiä poikia minäsuuntautuneempia. Pojat antoivat tyttöjä korkeampia kykyuskomusten arvoja itselleen kaikilla luokka-asteilla ja tämä tulos korostui 8- ja 9-luokkalaisten kohdalla. Oppilaiden tehtäväsuuntautuneisuus oli myönteisesti ja minäsuuntautuneisuus kielteisesti yhteydessä kykyuskomuksiin. Oppilaiden tehtävä- ja minäsuuntautuneisuus korreloivat keskenään. Yleisesti ottaen minäsuuntautuneisuus voimistui iän myötä. Sukupuoli huomioituna tyttöjen minäsuuntautuneisuus ja poikien tehtäväsuuntautuneisuus voimistuivat iän myötä. Tulosten perusteella näyttäisi siltä, että oppilaiden tehtäväsuuntautuneisuutta pitäisi tukea liikuntatunneilla, sillä tehtäväsuuntautuneisuus korreloi positiivisesti kykyuskomusten kanssa. Sen sijaan oppilaiden minäsuuntautuneisuutta vahvistavia opetusmenetelmiä olisi syytä välttää molempien sukupuolten kohdalla mutta erityisesti tyttöjen osalta. Tyttöjen kohdalla tulisi kiinnittää erityistä huomiota myös kykyuskomusten myönteiseen kehittämiseen. Mitä vanhemmista oppilaista on kyse, sitä enemmän edellä mainittuihin osa-alueisiin tulisi opetuksessa panostaa. Avainsanat: tavoiteorientaatio, tehtäväsuuntautuneisuus, minäsuuntautuneisuus, odotusarvoteoria, kykyuskomukset. Pirta Hiukka (2014). The differences between girls and boys of 5 to 9 grades in goal orientation and ability beliefs and trends of them. Department of Physical education, University of Jyväskylä, Master´s thesis, 65 pp., 3 appendicies. The aim of this study was to evaluate motivation behavior of 5-9 graders pupils in physical education classes and particularly how girls and boys differ in task-orientation, ego-orientation and ability beliefs. The differences in values of these variables were also examined between different grades generally, compared between genders and individually on both sexes behalf. The aim of this study was also to define how task- and ego-orientation of the years 2010 and 2011 and ability beliefs of the year 2011 were associated with each others. Additionally one goal was to get inform if there were any changes in pupils` task- and ego-orientations during the years 2010 and 2011 and was the gender connected with changes. Every comprehensive school of Sotkamo took apart of this study, exactly 11 primary schools and one lower secondary school. The aim of this study was to collect inform from same pupils during the time between both years in case that the sample of the year 2010 was 5-8 graders and of the year 2011 6-9 graders. In the year 2010 overall 525 pupils and in the year 2011 overall 566 pupils took apart of the study. In this study the final sample was finally consisted of those pupils who took apart identifiably in both years. Hereby the final sample was consisted by 182 pupils. The goal orientation was measured by the Finnish version (Liukkonen 1988) of Perception of Success Guestionnaire-indicator (Roberts et. all 1988). The ability beliefs were measured by the Finnish version (Ylipiipari 2011) of expectancy-value theory measurement (Eccles et. all 1983). In this study only three first questions of that measurement were considered. The internal consistency of measurements was analyzed by Cronbach´s alpha. The results were analyzed by independent and dependent samples t-test, one-way anova-test, Pearson product-moment correlation and repeated measures manova. There were not found any changes in task-orientation between genders. Instead, girls were clearly more ego-orientated than boys in both years. Especially at the year 2011 9th grade girls were significantly more ego-oriented than coeval boys. Boys gave higher values of ability beliefs than girls and especially in the grade 8th and 9th. Task-orientation was positively associated with ability beliefs whereas ego-orientation was negatively. The values of task- and ego-orientation correlated in some cases. Generally, students´ego-orientation increased and when gender was taken into account girls ego-orientation and boys task-orientation strengthened between years 2010 and 2011. According to results, students task-orientation should be promoted in physical education. Instead, methods which strengthen students ego-orientation should be avoided on both genders behalf but particularly on girls behalf. Teachers should also play special attention to the positive development of girls ability beliefs in physical education. The older students are the more teachers should concentare on facts above. Key words: goal orientation, task- orientation, ego-orientation, expectancy-value theory, ability beliefs

Published
2014

26. Microbial community structure and characteristics of the organic matter in soils under Pinus sylvestris, Picea abies and Betula pendula at two forest sites

Author

Susan J. Grayston, Risto Hiukka, Aino Smolander, Outi Priha, and Taina Pennanen

Subjects
chemistry.chemical_classification, biology, Chemistry, Soil organic matter, fungi, Scots pine, Soil Science, Picea abies, Mineralization (soil science), biology.organism_classification, Microbiology, Humus, Betula pendula, Botany, Organic matter, Soil fertility, Agronomy and Crop Science
Abstract

Microbial biomass C (Cmic), C mineralization rate, phospholipid fatty acid (PLFA) profiles and community level physiological profiles (CLPPs) using Biolog were determined from the humus and mineral soil layers in adjacent stands of Scots pine (Pinus sylvestris L.), Norway spruce [Picea abies (L.) Karst.] and silver birch (Betula pendula Roth) at two forest sites of different fertility. In addition, the Fourier-transformed infrared (FTIR) spectra were run on the samples for characterization of the organic matter. Cmic and C mineralization rate tended to be lowest under spruce and highest under birch, at the fertile site in all soil layers and at the less fertile site in the humus layer. There were also differences in microbial community structure in soils under different tree species. In the humus layer the PLFAs separated all tree species and in the mineral soil spruce was distinct from pine and birch. CLPPs did not distinguish microbial communities from the different tree species. The FTIR spectra did not separate the tree species, but clearly separated the two sites.

Published
2001
Full Text
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27. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Author

S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. Macfarlane, M Di Martino, G Bardini, Rossella Menghini, D Duhot, E Farcasiu, Annalisa Natalicchio, I Lindner, J Buvat, Christian L. Brand, Harry Dorchy, Iwona Pietrzak, Z T Luo, P Home, M Ekelund, Jesper Gromada, Kristine Færch, F Piarulli, H Kim, R Mentel, Zsuzsanna K. Zsengellér, Dullaart Rpf., Anton Luger, Thomas A. Pearson, V Manicardi, P Rösen, Feng Y-M., R Morganti, Lars Hansen, Demuth H-U., Haruo Kasai, A Shostak, Rudi Steffensen, G Taylor, Markolf Hanefeld, C Santini, E Hamaguchi, Roberto Miccoli, F Storms, M Cooper, Y Lee, Allison E. Aiello, P Smith, T Suehiro, K Treece, M Waluś, Timothy A Welborn, Simone Baltrusch, E Kontela, S Chai, J Crean, H Yokoyama, Johan G. Eriksson, Rafael Hernández Hernández, J Rodríguez-Saldaña, M P Tornero, G Formoso, D. Lovell, E Bingham, A Mylonakis, M Manteghetti, D Fedele, Antonio Martín-Duce, Ralph A. DeFronzo, D Salcedo, Kurt Højlund, Antonio Petrone, Sheu Whh., C Gutierrez, Flavia Pricci, S Kurita, Z G Abbas, M M Benedetti, Philippe A. Halban, Daniel J. Cox, O Ljungkvist, Justine Davies, J Palsgaard, Lars Sjöström, E Bosi, L Janin-Manificat, W. F. Kelly, M. Fernandez, E Colak, O V Mulyarchik, B Kronshage, F Lang, M Erfurth, Takashi Kadowaki, N Jendrike, U Walter, J Wishart, Y. Neye, D Kim, N Furuhashi, M Barsotti, D Florow, L Ke, L Borgquist, N C Jackson, Ffolliott M. Fisher, V Baskar, K Yoshioka, Bryan A. Wolf, G Chabrier, R Skoumal, Livio Luzi, H Kose, I Pharisien, B. Klein, H Winiarska, M C Johnson, L Griffiths, Nonna Kravchun, C Combe, Baptist Gallwitz, J Zdychova, L Skorda, Jorma Ilonen, W Gao, I N Steen, A Terrinoni, P D Ambery, W Kern, C M Kusminski, Cho M-H., Paolo Pozzilli, Louise G. Grunnet, E Schönle, David R Matthews, Robert W. Taylor, Y Cohen, Kim H-S., M P Eccles, N B Tutuncu, D McDowell, Richard M. Bergenstal, K Takamatsu, T Steiner, Jaan Palgi, Valdemar Grill, N Niculescu, G Federici, S Lehto, P. M. McKeigue, M Barone, Michael E. Trautmann, S Smirnov, J Mannion, M Eto, C Rousseau, M Conti, C S Ernest, Antonio Ceriello, D H Schweitzer, Jung E-D., Andreas Festa, Avijit Lahiri, A Shepelkevich, A Murro, A Kollmann, Jonathan R.S. Arch, R Landgraf, Son H-Y., I Engelsberger, E Agardh, S Rodríguez-Mulero, P J Kraml, K Lee, D. F. Du Toit, E Kim, G Fadini, Williams Ajk., Philip Home, M B Antcieferov, C Perlemoine, D Perrea, Song X-L., D Ruggieri, Krister Bokvist, Heidi Sørensen, Bilbao, G Yoshino, J P Taylor, Shen H-M., S M Furier, R Urquhart, J Wohlgelernter, Jianping Weng, T. Baba, Q Hong, C Silva, Castaigne J-P., M Felaco, X X Zhang, M Jaroň, Milla Rosengård-Bärlund, J G Papp, Toshio Miyata, Lervang H-H., Park M-K., I Kinalska, A Long, Oomen Phn., N Kogawa, Ippolita Patrizia Patera, S. Karadeniz, Dinesh Selvarajah, D S Chung, A Wensaas, Richard Imrich, M Recasens, J Ruxer, O Buchea, E Wilpart, S P Stepanenko, Le Ttd., H Ohgawara, Mariaconsuelo Valentini, A Mondok, M Peltonen, Marianne O. Larsen, K Chatzianagnostou, Agneta Ståhle, A L Ferrari, L Bordier, F Maingrette, A Matsuda, G Vukomanovic, Jakob D. Wikstrom, T Yamakita, E Gorostiaga, J Jin, B Gopalan, Heinz Drexel, S Hewitt, Rury R. Holman, C Dieterle, T L Ruchti, N Asatiani, M Sidira, A Iezzi, A J Sommerfield, D Châtenet, M L Olsen, R Bergemann, C Koehler, T L Kuraeva, B Balas, Christian Berne, E Santos-Mazo, G Smith, A Siejka, R Kožnarová, A Mattina, S Sheikh, A Adomeit, M Rasmussen, J. Fagerudd, N Busciantella Ricci, Nuria Vilarrasa, E Hammar, T L Thoms, L Aydın, Ron G. Rosenfeld, A Nikolajuk, R Gos, C L Morgan, H L Yu, D Dheelchand, S Ramrath, N Boudriga, Jerome I. Rotter, C Jahannault, W M Weston, Folke Lindgärde, M Hertlova, D Knight, A Monroy-Mayorga, E Pardini, A Chamson-Reig, B Franke, Janie McCluskey, Joseph Bryan, C Nikolopoulou, Christie M. Ballantyne, Fausto Santeusanio, L Pegoraro, M Lee, A Klimenko, S Jaiveer, K. Pettersson-Fernholm, Michael A. Nauck, A Ekbom-Schnell, G Deferrari, Riccardo Schiaffini, S. Pampanelli, Khan Aka., David Hopkins, Maija Wessman, M Kamarinos, Noh J-H., O Ebisui, K McCarroll, Jeppe Sturis, Peter Nowotny, N Gorbenko, Åke Sjöholm, David G. Maggs, A E Halseth, B Cresci, A A Ortiz-Gress, A Korakovouni, O Matejkova, C E Mogensen, C J Lin, Ramon Gomis, H Seaman, C Granier, Yang C-H., F Assah, O Sanchez, Fausto Machicao, Peter G. Morris, Alberto Ortiz, A Giardinelli, D Bracaglia, A Gonzalo, S Pavlatos, Andreas Lechner, F Canovic, L Sjolind, Allan Vaag, Birgitte Bruun Nielsen, David A. Ziegler, Vito Lampasona, R Gershoni-Baruch, A. Dei Cas, H Renz, E Mena, Matthew Waltham, Kim D-M., H Levanen, D D Mick, Valentina Alexandrovna Peterkova, E Meskhishvili, Sarah Nutland, R Bustani, John R. Lindsay, M Christoforidou, A Abicht, E Harno, K Cyganek, A Fitchet, S Neelotpol, P Nikishin, P Serradas, J Hinrichsen, M Halvorson, M Chovatia, B Voet, Jinny Willis, E Parretti, M Haslbeck, M Wellard, L Teng, Julio Wainstein, J S Fischer, K. Lalic, D Roggenland, I Gich, R Anwar, Maurizio Cassader, D Serota, X J Li, R J Schotzinger, Vilmundur Gudnason, Björn Zethelius, S A Wootton, W Andrzejewski, R Rezsohazy, R Gao, T Klimentova, T Mazurek, I Bruckner, C Dohrmann, R E James, G daSilva Xavier, Kim S-Y., A Dorca, Stuart J. Pocock, Terri J. Allen, I Giovos, P B Parab, N H Andersen, P Fotinakis, Miriam Cnop, H Lee, Norbert Tennagels, Omorodola I. Abatan, F Ailett, I. Lager, D Manzella, H Hut, Larry A. Distiller, G Lip, Lim S-K., Rong Zhang, T Tsuno, Steen Knudsen, M. Bajardi, Manuel Benito, Dai Sugimoto, Melvin J. Prince, D W Dunstan, D Rankins, K A Majali, G Ozansoy, Isabella Russo, S Uçak, G Annuzzi, R Talar-Wojnarowska, K Lange, S Neugebauer-Baba, Campbell H. Thompson, Eric Renard, P. D. Mountjoy, Z Morrison, Elizabeth A. Davis, Franco Cavallo, C Corvaja, R Antuña, Craig John Currie, H Linnebjerg, He Y-L., A J Palmer, Mariola R. Chacón, H Malinska, M. Jones, R Lichnovská, K Mandes, Paolo Tessari, T Mokhort, A Laina, H. L. Y. Chan, I Schmidt, R Banks, Richard G. IJzerman, L Ksinantova, G Setti, H Vaudry, A Gallo, V Spallone, Chen J-W., Thomas Danne, A Chong, M Hallschmid, S Aczel, S Hulme, N Islam, M Hosoi, P M Ternan, P Di Bartolo, N Bishara, T Shibasaki, Martin A. Osterhoff, Im S-S., M Jecht, T Hamaguchi, S Mattera, K Ways, Elizabeth Northam, U Rajala, Reinhard W. Holl, L Yang, S Panaiotopoulos, K Horvath, R Kluge, Thora B. Bodvarsdottir, Y Dong, Irene Alemanno, C McDougall, Reimar W. Thomsen, M Campbell, W Rabl, John Öhrvik, Yuichiro Yamada, Paola Ungaro, W Benzer, Mike Sampson, Roberto Trevisan, R G Radu, Aas A-M., P E Lobo, Ricardo Scott, S M Son, Josephine M. Forbes, T A Hillier, K L Wyne, Louis L. Nguyen, J Farmer, M H Tan, Kwon H-S., J Yang, L Sandvik, Franco Folli, A K Jenum, M Nguyen, W Pratipanawatr, A L Frederiksen, Rebecca Smith, Lee H-J., A Schäfer, C Manuelli, G S Denver, T Vukovich, B Maceira, K Matsumoto, K. Chokkalingam, Nurcan Üçeyler, P Modi, Timothy M. Morgan, S Mertens, B M Singh, Michaela Riedl, K Iso, C Cucurullo, G. F. Bottazzo, M Calvani, K Hur, J Wetzels, Kazuhiro Takahashi, Y Aso, H Stammer, M G Masding, Fitsum Guebre-Egziabher, J L González-Sánchez, L Armstrong, Alberto Maran, Peter G.F. Swift, S S Popovic, J Starczynski, E Vitacolonna, Luigi Laviola, R W Gelling, Marina Cardellini, D Barilla, Rosa de Diego Martínez, W H Landschulz, Anne Mette Rosenfalck, R K Wong, Kevin E. Schneider, K Peros, Giuseppe Nanni, F Zhang, I Rákóczi, T Iburi, M Nakhjavani, X Q Zhang, S Tournis, Per Lav Madsen, Graham A. Hitman, A. Tura, K Laubner, N D Kostic, Lawrence M. Dolan, R. Sinha Roy, J A Wagner, J. 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Leon, Alberti Gkm., A Opel, S Kokkoris, S B Hong, Philippe Courtois, L Haque, Maria Sörhede Winzell, M C Beauvois, A Szypowska, D Yu, M Gutniak, D Petzinna, B Isomaa, K S Prickett, Maria Felice Brizzi, Pavel Hamet, P J Hammond, K. F. Michelmore, Yumie Takeshita, N Hariharan, Corrado M. Cilio, G Pogatsa, W G Jerome, E Bartley, K Schlembacher, G Blohmó, Guy A. Rutter, Kyung Mook Choi, S. C Tamer, Felix K. Assah, K A Jandeleit-Dahm, M Chan, H Darius, Jørgen F. P. Wojtaszewski, A Papazisi, M Amaya, A Knopff, M Tadayyon, I J Kim, W Russ, T Myrnäs, M. Tryon, S Poonsatha, Noel Cameron, Kim M-H., Alejandra Tomas, F Homo-Dekarche, G. Di Cianni, M Stotzka, C Solimine, Mikhail Borisovich Antsiferov, H Naserke, M Bianchi-Biscay, J I Lara, Moon C-K., Alain Ktorza, Alison N. Jeffery, V Lilla, Eun Seok Kang, Hanley Ajg., J Widder, R Ratner, C Goretti, P J Weston, J Perkins, V Rasmussen, M Evans, T M Gibson, A Jaffe, S I Chisalita, C Owman, L Hiltunen, E Kakishita, C M Mack, H C Potter, M Femerling, M Desai, M Soinio, K Yang, Patricia L. Brubaker, M Meyer, V Dy, J Berden, R Komers, Milos Adamec, R Petzoldt, Alan G. Robinson, R Stevens, A Doi, A Leunda, Eduard Montanya, Alessandra K Cardozo, N Kraenkel, Claudio Cobelli, U A Mueller, S Yamashiro, B R Gedulin, G Francisco, J Dennenmoser, Lesch K-P., Martin G. Bischof, M Ichita, C Fernandes, Jochen Hampe, S Kern, D Kelly, E Zeender, P Perna, J D Best, A C Calkin, Vivian Fonseca, J Prestle, D G Parkes, Satish K. Garg, T Burrell, B M Fischer, D Kruger, J S Skinner, Lin T-M., Jozef Ukropec, Maria Jeziorska, K Arii, David D. D’Alessio, M B Gomes, L Quandt, I Fragaki, M C Brindisi, A Gladkih, E Kitsou, S Di Cola, T Iwasaki, Peter Diem, T Lakka, V V Popova, G Lee, Hannah J. 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Paulin, S, Marcu, S, Tauveron, I, Zimmermann, C, Schiele, F, Seronde, M, Vautrin, P, Lusson, J, Thieblot, P, Bernard, Y, Mistry, A, Pye, M, Peovska, I, Maksimovic Pavlovic, J, Vavlukis, M, Pop Gorceva, D, Bosevski, M, Scognamiglio, R, Negut, C, De Kreutzenberg, S, Madonna, R, De Caterina, R, Willerson, J, Geng, Y, Vahsen, S, Ledwig, D, Ramrath, S, Frantz, S, Schmidt, I, Calvillo, L, Dienesch, C, Elbing, I, Bischoff, H, Ertl, G, Bauersachs, J, Davydov, A, Mkrtum'Yan, A, Baranova, L, Ikeda, Y, Suehiro, T, Osaki, F, Ota, K, Arii, K, Kumon, Y, Hashimoto, K, Doney, A, Morris, A, Palmer, C, Byun, S, Doo, H, Pagnin, E, Calo, L, Fadini, G, Kubaszek, A, Chai, S, Chai, Q, Rasmussen, L, Ledet, T, Wogensen, L, Lengyel, C, Varró, A, Virág, L, Magyar, J, Bíró, T, Jost, N, Skoumal, R, Nánási, P, Tóth, M, Horkay, F, Papp, J, Zacharopoulou, O, Athanaselis, S, Tsokos, N, Doupis, J, Psallas, M, Cokkinos, D, Pavlatos, S, Liatis, S, Akhobadze, T, Dzneladze, L, Samarguliani, I, Taskiran, M, Rasmussen, V, Jensen, G, Fisher, A, Petrovsky, N, Srikusalanukul, W, Budge, M, Trifunovic zamaklar, D, Zivkovic, M, Jelic, V, Vukomanovic, G, Ristic, A, Seferovic, P, Costa, J, Duarte, S, Manley, S, Sailesh, S, Venkataraman, A, Haider, Y, Groza, I, Oprean, M, Ardelean, A, Morosanu, A, Darkow, T, Vanderplas, A, Mamas, M, Mcelduff, P, Burns, J, Edwards, R, Fitchet, A, Young, R, Gibson, J, Lichiardopol, R, Niculescu, N, Totora, A, Pencea, C, Tomescu, I, Cinteza, M, Manicardi, V, Coscelli, C, Navazio, A, Catellani, E, Michelini, M, Dall'Asta, D, Guberti, A, Piazza, A, Gasparini, E, Pantaleoni, M, Guiducci, U, Manari, A, Sejil, S, Janand delenne, B, Avierinos, J, Habib, G, Labastie, N, Vague, P, Lassmann vague, V, Luźniak, P, Tatoń, J, Wojciechowska Luźniak, A, Zairis, M, Lyras, A, Patsourakos, N, Tsirimbis, V, Foussas, S, Lupón, J, Urrutia, A, Herreros, J, González, B, Coll, R, Altimir, S, Prats, M, Valle, V, Abreu padí, C, Rábago, G, Ivanova, L, Brasacchio, D, Harno, E, Keenan, A, Li, H, Lu, Z, Ke, L, Liu, H, Jeong, I, Chae, M, Choi, M, Yoo, H, Kim, C, Yun, M, Na, M, Kang, Y, Kong, O, Son, S, Kim, I, Tanaka, N, Hosoi, M, Matsuyama, Y, Fukumoto, M, Yamakita, T, Yoshioka, K, Ishii, T, Sato, T, Fujii, S, Aoki, T, Shibata, T, Mizutani, N, Suzuki, J, Fowelin, J, Samuelsson, P, Brandrup wogsen, G, Okumura, K, Tokmakova, A, Staroverova, D, Antcieferov, M, Shutichina, I, Kuntchevich, G, Vriesendorp, T, Morélis, Q, Legemate, D, Schaper, F, Mainas, E, Gkioulmpasanis, I, Panagiotou, I, Vassilikos, G, Skorda, L, Sidira, M, Christoforidou, M, Alaveras, A, Artikis, V, Evdemon, E, Lechleitner, M, Koch, T, Ebenbichler, C, Sturm, W, Moretti, L, Moruzzo, D, Boldrini, E, Pandolfo, C, Kameyama, M, Iwasa, R, Cho, M, Nam, J, Huh, K, Kaplar, M, Paragh, G, Erdei, A, Csongradi, E, Garai, I, Varga, J, Galuska, L, Udvardy, M, Higa, M, Kaneko, Y, Hiroi, N, Koziarska, D, Nowacki, P, Majkowska, L, Luzniak, P, Wojciechowska luźniak, A, Tushuizen, M, Nieuwland, R, Snoeck, D, Sturk, A, Diamant, M, Aguiar, L, Bahia, L, Villela, N, Laflor, C, Conde, C, Bottino, D, Dorigo, D, Bouskela, E, Pu, S, Luo, Z, Lam, K, Dan, Q, Xu, A, Shen, J, Cheng, K, Xu, J, Thamer, C, Stefan, N, Haap, M, Heller, E, Tschritter, O, De Prado, A, Ortiz, A, Ybarra, J, Gich, I, Pou, J, Ehren, M, Roggenland, D, Reinsen, B, Klein, H, Rittig, K, Stock, J, Kocher, B, Balletshofer, B, Shon, H, Chung, D, Nakatani, Y, Matsuhisa, M, Kaneto, H, Hatazaki, M, Yoshiuchi, K, Katakami, N, Kawamori, D, Ohtoshi, K, Sakamoto, K, Matsuoka, T, Ozawa, K, Ogawa, S, Hori, M, Yamasaki, Y, Zitouni, K, Harry, D, Nourooz zadeh, J, Earle, K, Olesen, P, Franco, L, Corvaja, C, Semplicini, A, Ceylan işık, A, Arı, N, Rösen, P, Lee, I, Park, K, Jung, E, Shin, D, Jo, S, Obuobie, K, Prakash, P, Hanna, F, Lazarus, J, Varadhan, L, Gurushankar, J, James, D, Sheikh, S, Gaede, P, Zou, D, Vilarrasa, N, Perez maraver, M, Mena, E, Perez, D, Setti, G, Buckingham, R, Urbančič, V, Stefanovska, A, Bernjak, A, Ažman juvan, K, Kocijančič, A, Glowania, A, Filters, T, Fosmark, D, Torjesen, P, Kilhovd, B, Berg, T, Sandvik, L, Hanssen, K, Mentink, C, Donchenko, G, Stepanenko, S, Maingrette, F, Deng, H, Lindenmair, A, Freudenthaler, A, Baumgartner parzer, S, Nizheradze, K, Khoruzhenko, A, Tronko, N, Sheu, W, Ou, H, Shen, H, Lin, T, Wu, H, Yang, C, Mogylnytska, L, Schmoelzer, I, Davies, J, Band, M, Struthers, A, Prázný, M, Škrha, J, Kasalová, Z, Neelotpol, S, Jahan, P, Kauschke, S, Harrop, C, Schäfer, A, Widder, J, Eigenthaler, M, Walter, U, Uchimura, I, Ikebukuro, M, Kaibara, M, Hirata, M, Helal, R, Pervin, F, Yang, X, Jansson, P, Nagaev, I, Jack, M, Carvalho, E, Sunnerhagen, K, Cam, M, Cushman, S, Smith, U, Creely, S, Farmer, J, Gustafson, B, Kusminski, C, Krusinova, E, Wohl, P, Klementova, M, Lanska, V, Mcdougall, C, Kelly, I, Abbas, Z, Lutale, J, Archibald, L, Karunajeewa, H, Stingemore, N, Stuccio, G, Mcgechie, D, Muller, L, Hak, E, Goudzwaard, W, Montorsi, F, Homering, M, Sprenger, K, Goldstein, I, Asnaghi, V, Ferrari, G, Rastaldi, M, Gabellini, D, Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H

Subjects
0303 health sciences, medicine.medical_specialty, business.industry, EASD, Endocrinology, Diabetes and Metabolism, Human physiology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Family medicine, Internal Medicine, Medicine, business, 030217 neurology & neurosurgery, 030304 developmental biology
Published
2004

28. High Density Lipoprotein structural changes and drug response in lipidomic profiles following the long-term fenofibrate therapy in the FIELD substudy

Author

Heli Nygren, Matti Jauhiainen, Matej Orešič, Marianna Maranghi, Artturi Koivuniemi, Samuel Kaski, Ilkka Huopaniemi, Ilpo Vattulainen, Anne Hiukka, Laxman Yetukuri, Marja-Riitta Taskinen, Department of Applied Physics, Aalto-yliopisto, Aalto University, Helsinki Institute for Information Technology, Statistical Machine Learning and Bioinformatics research group / Samuel Kaski, Marja-Riitta Taskinen Research Group, Department of Medicine, Clinicum, and Institute for Molecular Medicine Finland

Subjects
Male, Time Factors, Homocysteine, Apolipoprotein A-II, lcsh:Medicine, 030204 cardiovascular system & hematology, Chemical Fractionation, Biochemistry, Analytical Chemistry, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Cluster Analysis, CRYSTAL-STRUCTURE, ta518, lcsh:Science, ta515, METABOLIC SYNDROME, 0303 health sciences, Multidisciplinary, Fenofibrate, 318 Medical biotechnology, ta213, Systems Biology, HEPATIC LIPASE, Lipids, 3. Good health, Chemistry, HDL INTERCONVERSION, Medicine, Female, PHOSPHOLIPID TRANSFER PROTEIN, lipids (amino acids, peptides, and proteins), Lipoproteins, HDL, medicine.drug, Research Article, medicine.medical_specialty, Drugs and Devices, HDL, Lipoproteins, education, APOLIPOPROTEIN-A-II, Biophysics, TYPE-2 DIABETES-MELLITUS, Cardiovascular Pharmacology, 03 medical and health sciences, Internal medicine, medicine, Humans, Computer Simulation, Biology, Computerized Simulations, CHOLESTEROL ACYLTRANSFERASE REACTION, 030304 developmental biology, ta113, ta112, Cholesterol, lcsh:R, Computational Biology, Proteins, nutritional and metabolic diseases, Lipid metabolism, HDL, lipidomics, fenofibrate, fenofibrate, MASS-SPECTROMETRY, medicine.disease, Lipid Metabolism, Endocrinology, Metabolism, chemistry, MOLECULAR-DYNAMICS, Multivariate Analysis, Computer Science, ta5141, lipidomics, lcsh:Q, Hepatic lipase, Metabolic syndrome
Abstract

VK: airc hiit In a recent FIELD study the fenofibrate therapy surprisingly failed to achieve significant benefit over placebo in the primary endpoint of coronary heart disease events. Increased levels of atherogenic homocysteine were observed in some patients assigned to fenofibrate therapy but the molecular mechanisms behind this are poorly understood. Herein we investigated HDL lipidomic profiles associated with fenofibrate treatment and the drug-induced Hcy levels in the FIELD substudy. We found that fenofibrate leads to complex HDL compositional changes including increased apoA-II, diminishment of lysophosphatidylcholines and increase of sphingomyelins. Ethanolamine plasmalogens were diminished only in a subgroup of fenofibrate-treated patients with elevated homocysteine levels. Finally we performed molecular dynamics simulations to qualitatively reconstitute HDL particles in silico. We found that increased number of apoA-II excludes neutral lipids from HDL surface and apoA-II is more deeply buried in the lipid matrix than apoA-I. In conclusion, a detailed molecular characterization of HDL may provide surrogates for predictors of drug response and thus help identify the patients who might benefit from fenofibrate treatment.

Published
2011
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29. Macrophage cholesterol efflux to plasma and HDL in subjects with low and high homocysteine levels: a FIELD substudy

Author

Jouko Sundvall, Robert M. Badeau, Matti Jauhiainen, Anne Hiukka, Marja-Riitta Taskinen, and Marianna Maranghi

Subjects
Male, medicine.medical_specialty, Homocysteine, High-Density Lipoproteins, Pre-beta, Placebo, Cohort Studies, chemistry.chemical_compound, Fenofibrate, Phospholipid transfer protein, Internal medicine, medicine, Distribution (pharmacology), Humans, Particle Size, Phospholipid Transfer Proteins, atherosclerosis, fenofibrate, hdl, homocysteine, Cells, Cultured, Aged, Cholesterol, Aryldialkylphosphatase, Macrophages, Hypertriglyceridemia, Reverse cholesterol transport, Cholesterol, HDL, Middle Aged, medicine.disease, Endocrinology, chemistry, Diabetes Mellitus, Type 2, lipids (amino acids, peptides, and proteins), Female, Cardiology and Cardiovascular Medicine, medicine.drug, Foam Cells
Abstract

Objectives Increases of homocysteine (Hcy) by fenofibrate correlated inversely to changes in HDL-C and apoA-I in the FIELD study. This finding raised the question whether high Hcy may influence HDL function and counteract benefits of fenofibrate on cardiovascular outcomes. In a subset of the FIELD study we investigated whether fenofibrate therapy or high Hcy, separately or in concert, modulate: (1) ability of plasma or HDL to facilitate cholesterol efflux from THP-1 foam cells; (2) plasma potential to generate preβ-HDL; (3) plasma phospholipid transfer protein (PLTP) activity, serum PON-1 mass and activity, HDL particle size and distribution. Methods We selected 33 subjects in the FIELD fenofibrate arm according to quartiles of Hcy at 5th year: 17 subjects were in the lowest (Low Hcy group) and 16 subjects were in the highest quartile (High Hcy group). In addition, 14 subjects allocated to placebo were matched by close-out Hcy levels to Low Hcy group. This design allowed us to examine the effects of both fenofibrate (comparison between placebo vs Low Hcy groups) and Hcy (comparison between close-out Low and High Hcy groups) on plasma and HDL ability to facilitate cellular cholesterol removal in the efflux assay in vitro using THP-1 foam cells. Results Hcy levels were 13.3 ± 0.7 μmol/L (placebo), 13.2 ± 2 μmol/L (Low Hcy) and 27.4 ± 6.5 μmol/L (High Hcy). Cholesterol efflux values to HDL and plasma, percentage of plasma preβ-HDL, PLTP activity, serum PON-1 mass and HDL particle size and distribution were similar in both fenofibrate groups and comparable to those of the placebo group. Conclusions In the present study cohort fenofibrate and high Hcy levels did not modulate HDL and plasma functions in the first step of reverse cholesterol transport, cholesterol efflux from foam cells.

Published
2010

30. PPAR alpha: an emerging therapeutic target in diabetic microvascular damage

Author

Anne Hiukka, Niina Matikainen, Marianna Maranghi, and Marja-Riitta Taskinen

Subjects
Angiogenesis, Endocrinology, Diabetes and Metabolism, Inflammation, Bioinformatics, Clofibric Acid, Endocrinology, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, PPAR alpha, Endothelial dysfunction, Dyslipidemias, Fenofibrate, business.industry, Hemodynamics, nutritional and metabolic diseases, medicine.disease, Lipotoxicity, Microvessels, Immunology, lipids (amino acids, peptides, and proteins), Metabolic syndrome, medicine.symptom, business, Dyslipidemia, medicine.drug
Abstract

The global pandemic of diabetes mellitus portends an alarming rise in the prevalence of microvascular complications, despite advanced therapies for hyperglycemia, hypertension and dyslipidemia. Peroxisome proliferator-activated receptor alpha (PPARalpha) is expressed in organs affected by diabetic microvascular disease (retina, kidney and nerves), and its expression is regulated specifically in these tissues. Experimental evidence suggests that PPARalpha activation attenuates or inhibits several mediators of vascular damage, including lipotoxicity, inflammation, reactive oxygen species generation, endothelial dysfunction, angiogenesis and thrombosis, and thus might influence intracellular signaling pathways that lead to microvascular complications. PPARalpha has emerged as a novel target to prevent microvascular disease, via both its lipid-related and lipid-unrelated actions. Despite strong experimental evidence of the potential benefits of PPARalpha agonists in the prevention of vascular damage, the evidence from clinical studies in patients with diabetes mellitus remains limited. Promising findings from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study on microvascular outcomes are countered by elevations in participants' homocysteine and creatinine levels that might potentially attenuate the benefits of PPARalpha activation. This Review focuses on the role of PPARalpha activation in diabetic microvascular disease and highlights the available experimental and clinical evidence from studies of PPARalpha agonists.

Published
2010

31. Effects of long-term fenofibrate treatment on markers of renal function in type 2 diabetes: the FIELD Helsinki substudy

Author

Carol, Forsblom, Anne, Hiukka, Eeva S, Leinonen, Jouko, Sundvall, Per-Henrik, Groop, and Marja-Riitta, Taskinen

Subjects
Blood Glucose, Male, Clinical Care/Education/Nutrition/Psychosocial Research, Blood Pressure, Middle Aged, urologic and male genital diseases, Kidney, Kidney Function Tests, Prognosis, Placebos, Diabetes Mellitus, Type 2, Fenofibrate, Creatinine, Albuminuria, Humans, Female, Triglycerides, Aged, Glomerular Filtration Rate, Hypolipidemic Agents, Original Research
Abstract

OBJECTIVE Although fenofibrate was associated with less progression of albuminuria in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, it is unknown if it has any effect on renal function. We explored if there were changes in commonly available markers of renal function during fenofibrate treatment in the FIELD Helsinki cohort excluding statin users. RESEARCH DESIGN AND METHODS One hundred and seventy subjects with type 2 diabetes were randomly assigned to micronized fenofibrate (200 mg/day) or placebo for 5 years. In this substudy, we measured several markers of albumin excretion and renal function. RESULTS After intensified treatment, blood pressure and fasting glucose decreased in both groups while A1C remained at 7.2%. Plasma creatinine increased with fenofibrate while urine creatinine remained comparable between the groups, resulting in significant decreases in both creatinine clearance and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD)-4 and Cockroft-Gault equations in the fenofibrate group. Cystatin C increased during fenofibrate treatment. Urinary albumin-to-creatinine ratio and diurnal urine protein remained unchanged, whereas overnight urinary albumin excretion rate showed minor decreases in both groups. CONCLUSIONS We report concomitant decreases in creatinine clearance and eGFR by fenofibrate. These changes complicate the clinical surveillance during fenofibrate treatment. We could not demonstrate the beneficial effects of fenofibrate on albumin excretion. A novel finding is the increase of cystatin C in type 2 diabetic patients during fenofibrate treatment. The clinical relevance of the changes needs to be assessed in a long-term outcome study of renal function.

Published
2009

32. Long-term effects of fenofibrate on carotid intima-media thickness and augmentation index in subjects with type 2 diabetes mellitus

Author

Olov Wiklund, Marja-Riitta Taskinen, Hannele Yki-Järvinen, Anthony C Keech, Jukka T. Salonen, Hiroshi Watanabe, E. Leinonen, Anne Hiukka, Jukka Westerbacka, Tomi-Pekka Tuomainen, and Lillemor Mattson Hultén

Subjects
Tunica media, Carotid Artery Diseases, Male, medicine.medical_specialty, Time Factors, Inflammation, Type 2 diabetes, augmentation index, Severity of Illness Index, Diabetes Complications, Double-Blind Method, Fenofibrate, Diabetes mellitus, Internal medicine, medicine, Humans, Treatment Failure, intima-media thickness, Aged, Hypolipidemic Agents, business.industry, Type 2 Diabetes Mellitus, Middle Aged, medicine.disease, Endocrinology, medicine.anatomical_structure, C-Reactive Protein, Carotid Arteries, Intima-media thickness, Diabetes Mellitus, Type 2, Circulatory system, Cardiology, Female, type 2 diabetes, medicine.symptom, business, Cardiology and Cardiovascular Medicine, Tunica Intima, Tunica Media, Biomarkers, medicine.drug, Acute-Phase Proteins
Abstract

ObjectivesThe aim of this substudy was to ascertain whether long-term treatment with fenofibrate reduces surrogate measures of atherosclerosis, biomarkers of inflammation, and endothelial activation in patients with type 2 diabetes.BackgroundSome fibrates may decrease cardiovascular events, improve endothelial function, and reduce levels of acute-phase proteins. In the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study, fenofibrate failed to decrease the primary end point of coronary events in patients with type 2 diabetes.MethodsA total of 170 patients with type 2 diabetes of the FIELD Helsinki cohort were randomly assigned to micronized fenofibrate 200 mg/day or placebo in a double-blind design. Carotid intima-media thickness (IMT) and the augmentation index (a measure of large artery stiffness) were measured at baseline and at second- and fifth-year visits. Plasma levels of interleukin (IL)-6, C-reactive protein (CRP), serum amyloid A (SAA), secretory phospholipase A2 IIA (SPLA2), E-selectin, vascular cellular adhesion molecule (VCAM)-1, and intercellular adhesion molecule (CAM)-1 were determined by commercial enzyme-linked immunosorbent assay kits at the same visits.ResultsIMT and the augmentation index increased similarly in both treatment groups during the study. Plasma levels of CRP, IL-6, SPLA2, SAA, VCAM-1, ICAM-1, and E-selectin remained unchanged in both groups.ConclusionsFenofibrate treatment was not associated with beneficial changes in IMT, augmentation index, or biomarkers of inflammation and endothelial function. (Fenofibrate Intervention and Event Lowering in Diabetes; NCT00132886)

Published
2008

33. Near-infrared characteristics of forest humus are correlated with soil respiration and microbial biomass in burnt soil

Author

Hannu Fritze, Petri Järvinen, and Risto Hiukka

Subjects
chemistry.chemical_classification, Ecology, Soil organic matter, Near-infrared spectroscopy, Soil Science, Microbiology, Humus, Soil respiration, chemistry, Environmental chemistry, Partial least squares regression, Respiration, Organic matter, Saturation (chemistry), Agronomy and Crop Science
Abstract

Near-infrared spectroscopy and soil physicochemical determinations (pHH2O, organic matter content, total C content, NH inf4 sup+ , total N content, cation-exchange capacity, and base saturation) were used to characterize fire-or wood ash-treated humus samples. The spectroscopic and the soil physicochemical analysis data from the humus samples were used separately to explain observed variations in soil respiration and microbial biomass C by partial least-square regression. The first regression component obtained from the physicochemical and spectroscopic characterization explained 10–12% and 60–80% of the biological variation, respectively. This suggests that information on organic material collected from near-infrared spectra is very useful for explaining biological variations in forest humus.

Published
1994
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34. High density lipoprotein structural changes and drug response in lipidomic profiles following the long-term fenofibrate therapy in the FIELD substudy

Author

Yetukuri, Laxman, Huopaniemi, Ilkka, Koivuniemi, Artturi, Maranghi, Marianna, Hiukka, Anne, Nygren, Heli, Kaski, Samuel, Taskinen, Marja-Riitta, Vattulainen, Ilpo, Jauhiainen, Matti, Oresic, Matej, Yetukuri, Laxman, Huopaniemi, Ilkka, Koivuniemi, Artturi, Maranghi, Marianna, Hiukka, Anne, Nygren, Heli, Kaski, Samuel, Taskinen, Marja-Riitta, Vattulainen, Ilpo, Jauhiainen, Matti, and Oresic, Matej

Abstract

In a recent FIELD study the fenofibrate therapy surprisingly failed to achieve significant benefit over placebo in the primary endpoint of coronary heart disease events. Increased levels of atherogenic homocysteine were observed in some patients assigned to fenofibrate therapy but the molecular mechanisms behind this are poorly understood. Herein we investigated HDL lipidomic profiles associated with fenofibrate treatment and the drug-induced Hcy levels in the FIELD substudy. We found that fenofibrate leads to complex HDL compositional changes including increased apoA-II, diminishment of lysophosphatidylcholines and increase of sphingomyelins. Ethanolamine plasmalogens were diminished only in a subgroup of fenofibrate-treated patients with elevated homocysteine levels. Finally we performed molecular dynamics simulations to qualitatively reconstitute HDL particles in silico. We found that increased number of apoA-II excludes neutral lipids from HDL surface and apoA-II is more deeply buried in the lipid matrix than apoA-I. In conclusion, a detailed molecular characterization of HDL may provide surrogates for predictors of drug response and thus help identify the patients who might benefit from fenofibrate treatment.

Published
2011
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35. Susceptibility of defoliated Scots pine to spontaneous and induced attack by Tomicus piniperda and Tomicus minor

Author

Martti Varama, Pekka Niemelä, Risto Hiukka, Bo Långström, and Erkki Annila

Subjects
Biomass (ecology), Diprionidae, biology, business.industry, Ecological Modeling, Scots pine, Pest control, Forestry, biology.organism_classification, chemistry.chemical_compound, Tomicus piniperda, Diflubenzuron, chemistry, Botany, lcsh:SD1-669.5, lcsh:Forestry, business, Diprion pini, Woody plant
Abstract

In 1990–1991, Diprion pini extensively defoliated Scots pine (Pinus sylvestris L.) trees in Lauhanvuori National Park in southwestern Finland. Many trees lost all their foliage, while others had ca. 10% foliage left after the second year of defoliation. Outside the national park, many nearby stands were also heavily defoliated in 1990, but were sprayed with diflubenzuron (Dimilin®) in 1991. This protected the current year needles, corresponding to ca 30% of full foliage. In spring 1992, pine trees with 0, 10, 30 and 100% foliage remaining (10 small and 10 large trees in each category) were baited with pine bolts to induce stem attacks by pine shoot beetles. All baited trees were attacked by Tomicus piniperda and some by T. minor. The attacks failed in all these trees except those that were totally defoliated and some of the small trees with 10% foliage left. Many unbaited trees escaped attack entirely, but only totally defoliated trees were successfully colonized (i.e. produced brood). Attack densities and brood production figures peaked in baited, large and totally defoliated trees. None of the measures (cambial electrical resistance, resin flow, induced lesion length by fungal inoculation, amount of hydrocarbons or phenolic compounds) used to describe tree vigour at the time of attack gave better information than the estimated remaining foliage. We conclude that the risk for beetle-induced mortality following defoliation is a function of remaining needle biomass and beetle pressure. Even at high beetle densities (as was simulated by baiting of trees), trees with 10% of the foliage remaining were able to defend themselves against attacking pine shoot beetles.

Published
1999
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36. High Density Lipoprotein Structural Changes and Drug Response in Lipidomic Profiles following the Long-Term Fenofibrate Therapy in the FIELD Substudy

Author

Yetukuri, Laxman, primary, Huopaniemi, Ilkka, additional, Koivuniemi, Artturi, additional, Maranghi, Marianna, additional, Hiukka, Anne, additional, Nygren, Heli, additional, Kaski, Samuel, additional, Taskinen, Marja-Riitta, additional, Vattulainen, Ilpo, additional, Jauhiainen, Matti, additional, and Orešič, Matej, additional

Published
2011
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38. Correction: PPARα: an emerging therapeutic target in diabetic microvascular damage

Author

Marja-Riitta Taskinen, Marianna Maranghi, Niina Matikainen, and Anne Hiukka

Subjects
Endocrinology, business.industry, Endocrinology, Diabetes and Metabolism, Section (typography), Physiology, Medicine, Bioinformatics, business
Abstract

Nat. Rev. Endocrinol. 6, 454–463 (2010); doi:10.1038/nrendo.2010.89 In the August 2010 issue of Nature Reviews Endocrinology in the reference section of this article, the name of the first author of reference 75 should have read SanGiovanni, J. P. and not San Giovanni, J. P.

Published
2010
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39. Long-Term Effects of Fenofibrate on Carotid Intima-Media Thickness and Augmentation Index in Subjects With Type 2 Diabetes Mellitus

Author

Hiukka, Anne, primary, Westerbacka, Jukka, additional, Leinonen, Eeva S., additional, Watanabe, Hiroshi, additional, Wiklund, Olov, additional, Hulten, Lillemor Mattson, additional, Salonen, Jukka T., additional, Tuomainen, Tomi-Pekka, additional, Yki-Järvinen, Hannele, additional, Keech, Anthony C., additional, and Taskinen, Marja-Riitta, additional

Published
2008
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40. Decreased High-Density Lipoprotein (HDL) Particle Size, Preβ-, and Large HDL Subspecies Concentration in Finnish Low-HDL Families

Author

Watanabe, Hiroshi, primary, Söderlund, Sanni, additional, Soro-Paavonen, Aino, additional, Hiukka, Anne, additional, Leinonen, Eeva, additional, Alagona, Corradina, additional, Salonen, Riitta, additional, Tuomainen, Tomi-Pekka, additional, Ehnholm, Christian, additional, Jauhiainen, Matti, additional, and Taskinen, Marja-Riitta, additional

Published
2006
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41. Acid-catalyzed Hydrolysis of Bridged Bi- and Tricyclic Compounds. XXIV. A Kinetic Method for Determination of Protonation Site in Hydration of 5-Substituted 2-Norbornenes

Author

Eeva Ottoila, Martti Lajunen, Antti Vesala, Jorma Arpalahti, and Risto Hiukka

Subjects
chemistry.chemical_classification, Acid catalysis, Hydrolysis, chemistry.chemical_compound, Reaction rate constant, Bicyclic molecule, Deuterium, Chemistry, General Chemical Engineering, Organic chemistry, Protonation, Perchloric acid, Tricyclic
Published
1985
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42. Acid-catalyzed hydrolysis of bridged bi- and tricyclic compounds. 25. Comparison of the hydrations of 2-methyl-2-norbornene and 2-methylenenorbornane with those of 1-methylcyclohexene and methylenecyclohexane

Author

Martti Lajunen and Risto Hiukka

Subjects
chemistry.chemical_classification, Hydrolysis, chemistry.chemical_compound, Acid catalysis, Aqueous solution, Hydrocarbon, Reaction rate constant, chemistry, Bicyclic molecule, Organic Chemistry, Methylenecyclohexane, Organic chemistry, Perchloric acid
Published
1986
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43. The Spotlight, Volume 6, Number 8, Thomson High School, Esko, Minnesota

Author

Wainio, William; Hendrickson, Frederick; Dyer, Frances; Maki, Velma; Lassila, Elton; Ware, Viljo; Johnson, Shirley Faye; Larson, Forrest; Francisco, Anthony; Francisco, Mary; Hiukka, Lauren; Kauppi, Harry; Maki, Velma; Juutilainen, Helen; Hallback, Marjorie; Osvold, Kenneth; Thoen, Betty; Koivisto, Oswald; Olson, Phyllis; Erkkila, Esther; Maki, Ainie; Comfort, Mardell; Johnson, John; Nelson, Mildred; Polo, Shirley; Pederson, Stella; Moen, Clareice; Heino, Vienna, Thomson Township High School, Wainio, William; Hendrickson, Frederick; Dyer, Frances; Maki, Velma; Lassila, Elton; Ware, Viljo; Johnson, Shirley Faye; Larson, Forrest; Francisco, Anthony; Francisco, Mary; Hiukka, Lauren; Kauppi, Harry; Maki, Velma; Juutilainen, Helen; Hallback, Marjorie; Osvold, Kenneth; Thoen, Betty; Koivisto, Oswald; Olson, Phyllis; Erkkila, Esther; Maki, Ainie; Comfort, Mardell; Johnson, John; Nelson, Mildred; Polo, Shirley; Pederson, Stella; Moen, Clareice; Heino, Vienna, and Thomson Township High School

Abstract

New junior high English teacher, Miss Clarice Moen, was introduced. The Girls' Glee Club and Superintendent A. L. Winterquist attempted to get a phonograph to be used at the skating rink. An article urging students to buy the bi-annual Lincoln Log yearbook was included. The Spotlight issues from September to January were entered in the contest of the National Scholastic Press. The band held a skating party. A pep rally was held to raise school spirit for the Carlton basketball game. Superintendent A. L. Winterquist wrote a sobering editorial urging students to think critically, with the world problems and war looming. Sophomore students wrote to international students and received some replies. A junior high assembly focused on thrift. In basketball, Thomson beat Floodwood as well as Grand Marais, but Carlton and Moose Lake beat Thomson. In FFA news, an FFA library was established. The FFA sponsored a Finnish movie, with proceeds to be divided between the FFA Chapter and the Finnish Benefit Fund at the Lincoln School. FFA boys worked on speeches for the public speaking contest. The Esko FFA chapter published the district news letter.

Published
1939

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