Chronic and acute stress in atherosclerosis : the role of endothelial function and arterial elasticity

Atherosclerosis is the main underlying pathology of coronary heart disease. Coronary heart disease is a serious health problem in Finland, and it is the leading cause of morbidity and mortality in industrialized countries. Psychological stress correlates with coronary heart disease events – myocardial infarction and sudden death, which are the most common clinical syndromes of atherosclerotic narrowing of arteries. The present series of studies examines the interaction between stress and endothelial function in relation to atherosclerosis. The study also aims to give new information on the mechanisms through which stress has its effect on atherosclerosis progression, focusing on possible relations between psychological stress and the functioning of the endothelium. Our project is based on data from one of the largest national epidemiological studies, the Cardiovascular Risk in Young Finns study, which has monitored the development of risk factors for coronary heart disease in 3596 young adults since 1980. The present study combines experimental stress research with epidemiology and uses an advanced method for examining atherosclerosis development in healthy subjects (intima-media thickness ultrasound measurement). The physiological parameters used were heart rate, respiratory sinus arrhythmia and pre-ejection period. Chronic stress was assessed by vital exhaustion. The ultrasound measurements that served as the indexes of preclinical atherosclerosis were carotid intima-media thickness, brachial flow-mediated dilatation and carotid artery compliance. The effects of cardiovascular risk factors found to be important were taken into account: serum cholesterols level, triglyceride level, serum insulin level and systolic and diastolic blood pressure. There were 69, 1596, 81 and 1721 participants in studies I-IV, respectively. The results showed that both chronic and acute stress may exert an effect on atherosclerosis in subjects with impaired endothelial responses. The findings are consistent with the idea that risk factors are more harmful if the endothelium is not working properly. Chronic stress was found to be a risk if it has resulted in ineffective cardiac stress reactivity or delayed recovery. Men were shown to be at increased risk for atherosclerotic progression in early life, which suggests men’s decreased stress coping ability in relation to stressful psychosocial coronary risk factors. Autonomic imbalance may be the common mechanism of the stress influence on atherosclerosis development. The results of the present study contain background information for the identification the first stages of atherosclerosis, and they may be useful for preventive medicine programs for young adults and could help to improve cardiovascular health in Finland as well as in other countries.

Preterm birth and risk factors for chronic disease : Helsinki Study of Very Low Birth Weight Adults

Background: The improved prognosis of early preterm birth has created a generation of surviving very low birth weight (< 1500 g, VLBW) infants whose health risks in adulthood are poorly known. Of every 1000 live-born infants in Finland, about 8 are born at VLBW. Variation in birth weight, even within the normal range, relates to considerable variation in the risk for several common adult disorders, including cardiovascular disease and osteoporosis. Small preterm infants frequently exhibit severe postnatal or prenatal growth retardation, or both. Much reason for concern thus exists, regarding adverse health effects in surviving small preterm infants later lives. We studied young adults, aiming at exploring whether VLBW birth and postnatal events after such a birth are associated with higher levels of risk factors for cardiovascular disease or osteoporosis. Subjects and Methods: A follow-up study for VLBW infants began in 1978; by the end of 1985, 335 VLBW survivors at Helsinki University Central Hospital participated in the follow-up. Their gestational ages ranged from 24 to 35 weeks, mean 29.2 and standard deviation 2.2 weeks. In 2004, we invited for a clinic visit 255 subjects, aged 18 to 27, who still lived in the greater Helsinki area. From the same birth hospitals, we also invited 314 term-born controls of similar age and sex. These two study groups underwent measurements of body size and composition, function of brachial arterial endothelium (flow-mediated dilatation, FMD) and carotid artery intima-media thickness (cIMT) by ultrasound. In addition, we measured plasma lipid concentrations, ambulatory blood pressure, fasting insulin, glucose tolerance and, by dual-energy x-ray densitometry, bone-mineral density. Results: 172 control and 166 VLBW participants underwent lipid measurements and a glucose tolerance test. VLBW adults fasting insulin (adjusted for body mass index) was 12.6% (95% confidence interval, 0.8 to 25.8) higher than that of the controls. The glucose and insulin concentrations 120 minutes after 75 g glucose ingestion showed similar differences (N=332) (I). VLBW adults had 3.9 mmHg (1.3 to 6.4) higher office systolic blood pressure, 3.5 mmHg (1.7 to 5.2) higher office diastolic blood pressure (I), and, when adjusted for body mass index and height, 3.1 mmHg (0.5 to 5.5) higher 24-hour mean systolic blood pressure (N=238) (II). VLBW birth was associated neither with HDL- or total cholesterol nor triglyceride concentrations (N=332) (I), nor was it associated with a low FMD or a high cIMT (N=160) (III). VLBW adults had 0.51-unit (0.28 to 0.75) lower lumbar spine Z scores and 0.56-unit (0.34 to 0.78) lower femoral neck Z scores (N=283). Adjustments for size attenuated the differences, but only partially (IV). Conclusions: These results imply that those born at VLBW, although mostly healthy as young adults, already bear several risk factors for chronic adult disease. The significantly higher fasting insulin level in adults with VLBW suggests increased insulin resistance. The higher blood pressure in young adults born at VLBW may indicate they later are at risk for hypertension, although their unaffected endothelial function may be evidence for some form of protection from cardiovascular disease. Lower bone mineral density around the age of peak bone mass may suggest increased risk for later osteoporotic fractures. Because cardiovascular disease and osteoporosis are frequent, and their prevention is relatively cheap and safe, one should focus on prevention now. When initiated early, preventive measures are likely to have sufficient time to be effective in preventing or postponing the onset of chronic disease.

Preterm birth and risk factors for chronic disease : Helsinki Study of Very Low Birth Weight Adults

Background: The improved prognosis of early preterm birth has created a generation of surviving very low birth weight (PIENEMPI KUIN 1500 g, VLBW) infants whose health risks in adulthood are poorly known. Of every 1000 live-born infants in Finland, about 8 are born at VLBW. Variation in birth weight, even within the normal range, relates to considerable variation in the risk for several common adult disorders, including cardiovascular disease and osteoporosis. Small preterm infants frequently exhibit severe postnatal or prenatal growth retardation, or both. Much reason for concern thus exists, regarding adverse health effects in surviving small preterm infants later lives. We studied young adults, aiming at exploring whether VLBW birth and postnatal events after such a birth are associated with higher levels of risk factors for cardiovascular disease or osteoporosis. Subjects and Methods: A follow-up study for VLBW infants began in 1978; by the end of 1985, 335 VLBW survivors at Helsinki University Central Hospital participated in the follow-up. Their gestational ages ranged from 24 to 35 weeks, mean 29.2 and standard deviation 2.2 weeks. In 2004, we invited for a clinic visit 255 subjects, aged 18 to 27, who still lived in the greater Helsinki area. From the same birth hospitals, we also invited 314 term-born controls of similar age and sex. These two study groups underwent measurements of body size and composition, function of brachial arterial endothelium (flow-mediated dilatation, FMD) and carotid artery intima-media thickness (cIMT) by ultrasound. In addition, we measured plasma lipid concentrations, ambulatory blood pressure, fasting insulin, glucose tolerance and, by dual-energy x-ray densitometry, bone-mineral density. Results: 172 control and 166 VLBW participants underwent lipid measurements and a glucose tolerance test. VLBW adults fasting insulin (adjusted for body mass index) was 12.6% (95% confidence interval, 0.8 to 25.8) higher than that of the controls. The glucose and insulin concentrations 120 minutes after 75 g glucose ingestion showed similar differences (N=332) (I). VLBW adults had 3.9 mmHg (1.3 to 6.4) higher office systolic blood pressure, 3.5 mmHg (1.7 to 5.2) higher office diastolic blood pressure (I), and, when adjusted for body mass index and height, 3.1 mmHg (0.5 to 5.5) higher 24-hour mean systolic blood pressure (N=238) (II). VLBW birth was associated neither with HDL- or total cholesterol nor triglyceride concentrations (N=332) (I), nor was it associated with a low FMD or a high cIMT (N=160) (III). VLBW adults had 0.51-unit (0.28 to 0.75) lower lumbar spine Z scores and 0.56-unit (0.34 to 0.78) lower femoral neck Z scores (N=283). Adjustments for size attenuated the differences, but only partially (IV). Conclusions: These results imply that those born at VLBW, although mostly healthy as young adults, already bear several risk factors for chronic adult disease. The significantly higher fasting insulin level in adults with VLBW suggests increased insulin resistance. The higher blood pressure in young adults born at VLBW may indicate they later are at risk for hypertension, although their unaffected endothelial function may be evidence for some form of protection from cardiovascular disease. Lower bone mineral density around the age of peak bone mass may suggest increased risk for later osteoporotic fractures. Because cardiovascular disease and osteoporosis are frequent, and their prevention is relatively cheap and safe, one should focus on prevention now. When initiated early, preventive measures are likely to have sufficient time to be effective in preventing or postponing the onset of chronic disease.

Mediated music makers : Constructing author images in popular music

The subject of the thesis is the mediated construction of author images in popular music. In the study, the construction of images is treated as a process in which artists, the media and the members of the audience participate. The notions of presented, mediated and compiled author images are used in explaining the mediation process and the various authorial roles of the agents involved. In order to explore the issue more closely, I analyse the author images of a group of popular music artists representing the genres of rock, pop and electronic dance music. The analysed material consists mostly of written media texts through which the artists authorial roles and creative responsibilities are discussed. Theoretically speaking, the starting points for the examination lie in cultural studies and discourse analysis. Even though author images may be conceived as intertextual constructions, the artist is usually presented as a recognizable figure whose purpose is to give the music its public face. This study does not, then, deal with musical authors as such, but rather with their public images and mediated constructions. Because of the author-based functioning of popular music culture and the idea of the artist s individual creative power, the collective and social processes involved in the making of popular music are often superseded by the belief in a single, originating authorship. In addition to the collective practices of music making, the roles of the media and the marketing machinery complicate attempts to clarify the sharing of authorial contributions. As the case studies demonstrate, the differences between the examined author images are connected with a number of themes ranging from issues of auteurism and stardom to the use of masked imagery and the blending of authorial voices. Also the emergence of new music technologies has affected not only the ways in which music is made, but also how the artist s authorial status and artistic identity is understood. In the study at hand, the author images of auteurs, stars, DJs and sampling artists are discussed alongside such varied topics as collective authorship, evaluative hierarchies, visual promotion and generic conventions. Taken altogether, the examined case studies shed light on the functioning of popular music culture and the ways in which musical authorship is (re)defined.

Personality and social psychological studies on computer-mediated communication in school settings

The present study examined how personality and social psychological factors affect third and fourth graders' computer-mediated communication. Personality was analysed in terms of the following strategies: optimism, pessimism and defensive pessimism. Students worked either individually or in dyads which were paired homogeneously or heterogeneously according to the strategies. Moreover, the present study compared horizontal and vertical interaction. The study also examined the role that popularity plays, and students were divided into groups based on their popularity level. The results show that an optimistic strategy is useful. Optimism was found to be related to the active production and processing of ideas. Although previous research has identified drawbacks to pessimism in achievement settings, this study shows that the pessimistic strategy is not as debilitating a strategy as is usually assumed. Pessimistic students were able to process their ideas. However, defensive pessimists were somewhat cautious in introducing or changing ideas. Heterogeneous dyads were not beneficial configurations with respect to producing, introducing, or changing ideas. Moreover, many differences were found to exist between the horizontal and vertical interaction; specifically, the students expressed more opinions and feelings when teachers took no part in the discussions. Strong emotions were observed especially in the horizontal interaction. Further, group working skills were found to be more important for boys than for girls, while rejected students were not at a disadvantage compared to popular ones. Schools can encourage emotional and social learning. The present study shows that students can use computers to express their feelings. In addition, students who are unpopular in non-computer contexts or students who use pessimism can benefit from computers. Participation in computer discussions can give unpopular children a chance to develop confidence when relating to peers.

Mikä yliopisto-opiskelijaa kiihdyttää? : Opiskeluympäristöjen tutkimusta CASS-kokemusotantamenetelmällä flow-teoriaa ja ydintunneteorioita soveltaen

Flow experience is often defined either as an experience of high concentration and enjoyment or as a situation, where high challenges are matched with high skills. According to core-emotion theories, the experience of any emotion contains two core emotions: valence and arousal. Through an accurate mathematical model, the present study investigated, whether the experience of concentration and enjoyment is related to situations where both challenge and skills are high and in balance. Further, it was investigated what sort of core emotions are related to differing relationships between challenge and skills. Finally, university students’ experiences of their natural study environments were described in terms of core emotions and in terms of relationships between challenge and skills. Participants were 55 university students who participated two weeks research period. Altogether 3367 questionnaire answers were collected with the CASS experience-sampling method, operating in 3G-mobile phones. The relationship between challenge and skills (competence) was defined in an exact way in polar coordinates. An enjoyable and concentrated flow experience was defined as a sum variable of absorption, interest and enthusiasm. Core emotions were calculated with factor analysis from nine emotion variables. As expected, an experience of concentration and enjoyment was, on average, related to the situations where both challenge and skills were high and in balance. This was not, however, the case in every situation. Thus, it should be taken into consideration how flow experience is operationalised in experience sampling studies. When flow experience was defined as a situation of high challenge and high skills, it was often related to high valence and arousal emotions such as excitement or enthusiasm. A happier or a more tranquil enjoyment was related to situations of moderate challenge and high skills. Experiences differed clearly between various natural study environments. At lectures students were often bored or mentally absent, and did not experience challenges. In a small group students were often excited or enthusiastic, and showed optimal balance between challenge and skills. At library students felt satisfied and were engaged in highly challenging work.

Pelaamiskokemukset ja pelaamisen yksilöllisten merkitysten yhteys flow n kokemiseen

The main goal of this study was to explore experiences induced by playing digital games (i.e. meaning of playing). In addition, the study aimed at structuring the larger entities of gaming experience. This was done by using theory-driven and data grounded approaches. Previously gaming experiences have not been explored as a whole. The consideration of gaming experiences on the basis of psychological theories and studies has also been rare. The secondary goal of this study was to clarify, whether the individual meanings of playing are connected with flow experience in an occasional gaming situation. Flow is an enjoyable experience and usually activities that induce flow are gladly repeated. Previously, flow has been proved to be an essential concept in the context of playing, but the relations between meanings of playing and flow have not been studied. The relations between gender and gaming experiences were examined throughout the study, as well as the relationship between gaming frequency and experiences. The study was divided into two sections, of which the first was composed according to the main goals. Its data was gathered by using an Internet questionnaire. The other section covered the themes that were formulated on the basis of the secondary aims. In that section, the participants played a driving game for 40 minutes and then filled in a questionnaire, which measured flow related experiences. In both sections, the participants were mainly young Finnish adults. All the participants in the second section (n = 60) had already participated in the first section (n = 267). Both qualitative and quantitative research techniques were used in the study. In the first section, freely described gaming experiences were classified according to the grounded theory. After that, the most common categories were further classified into the basic structures of gaming experience, some according to the existing theories of experience structure and some according to the data (i.e. grounded theory). In the other section flow constructs were measured and used as grouping variables in a cluster analysis. Three meaningful groups were compared regarding the meanings of gaming that were explored in the first section. The descriptions of gaming experiences were classified into four main categories, which were conceptions of the gaming process, emotions, motivations and focused attention. All the theory-driven categories were found in the data. This frame of reference can be utilized in future when reliability and validity of already existing methods for measuring gaming experiences are considered or new methods will be developed. The connection between the individual relevance of gaming and flow was minor. However, as the scope was specified to relations between primary meanings of playing and flow, it was noticed that attributing enjoyment to gaming did not lead to the strongest flow-experiences. This implies that the issue should be studied more in future. As a whole this study proves that gamer-related research from numerous vantage points can benefit from concentrating on gaming experiences.

Psychophysiology of flow experience : An explorative study

This study explored the possibilities the psychophysiological methodology offer to flow research. Facial electromyography has often been used to index valence, and electrodermal activity to index arousal, the two basic dimensions of emotion. It was hypothesized that these measures can also be used to examine enjoyment, a basic component of flow experiment. A digital game was used to induce flow, and physiological activity of 32 subjects was measured continuously. Flow State Scale was used to assess flow. Activity of corrugator supercilii muscle, an index of negative valence, was negatively correlated with flow reports, as hypothesized. Contrary to hypothesis, skin conductance level, an index of arousal, was unrelated to self-reported flow. The results for association between flow and zygomaticus major and orbicularis oculi muscle activities, indices of positive valence, were inconclusive, possibly due to experimental design where only tonic measures were available. Psychophysiological methods are recommended for future studies of flow. Specifically, the time series approach may be particularly viable in examining the temporal aspects of flow, an area currently unexplored. Furthermore, it is suggested that digital game research would benefit from psychophysiological study of game-related flow.

Levosimendan: Studies on its mechanisms of action and beyond

Acute heart failure syndrome represents a prominent and growing health problem all around the world. Ideally, medical treatment for patients admitted to hospital because of this syndrome, in addition to alleviating the acute symptoms, should also prevent myocardial damage, modulate neurohumoral and inflammatory activation, and preserve or even improve renal function. Levosimendan is a cardiac enhancer having both inotropic and vasodilatory effects. It is approved for the short-term treatment of acutely decompensated chronic heart failure, but it has been shown to have beneficial clinical effects also in ischemic heart disease and septic shock as well as in perioperative cardiac support. In the present study, the mechanisms of action of levosimendan were studied in isolated guinea-pig heart preparations: Langendorff-perfused heart, papillary muscle and permeabilized cardiomyocytes as well as in purified phosphodiesterase isoenzyme preparations. Levosimendan was shown to be a potent inotropic agent in isolated Langendorff-perfused heart and right ventricle papillary muscle. In permeabilized cardiomyocytes, it was demonstrated to be a potent calcium sensitizer in contrast to its enantiomer, dextrosimendan. It was additionally shown to be a very selective phosphodiesterase (PDE) type-3 inhibitor, the selectivity factor for PDE3 over PDE4 being 10000 for levosimendan. Irrespective of this very selective PDE3 inhibitory property in purified enzyme preparations, the inotropic effect of levosimendan was demonstrated to be mediated mainly through calcium sensitization in the isolated heart as well as the papillary muscle preparations at clinically relevant concentrations. In the isolated Lagendorff-perfused heart, glibenclamide antagonized the levosimendan-induced increase in coronary flow (CF). Therefore, the main vasodilatory mechanism in coronary veins is believed to be the opening of the ATP-sensitive potassium (KATP) channels. In the paced hearts, CF did not increase in parallel with oxygen consumption (MVO2), thus indicating that levosimendan had a direct vasodilatory effect on coronary veins. The pharmacology of levosimendan was clearly different from that of milrinone, which induced an increase in CF in parallel with MVO2. In conclusion, levosimendan was demonstrated to increase cardiac contractility by binding to cardiac troponin C and sensitizing the myofilament contractile proteins to calcium, and further to induce coronary vasodilatation by opening KATP channels in vascular smooth muscle. In addition, the efficiency of the cardiac contraction was shown to be more advantageous when the heart was perfused with levosimendan in comparison to milrinone perfusion.

The role of pollen in the changing environmental conditions of Scots pine

Rapid change in climate is challenge for the adaptation of forest trees in the future. In wind pollinated tree species pollen mediated long distance gene flow may provide alleles that are (pre)adapted to a future climate. In order to examine the long distance pollen flow in Scots pine (Pinus sylvestris L.), we measured the amount and viability of airborne pollen and flowering phenology in central, northern, and northernmost Finland during four years. Viable airborne pollen grains were detected during female flowering and before local pollen shedding in all study sites. The situation when there was nonlocal pollen in the air lasted from one to four days depending on the year and study site. The amount of nonlocal airborne pollen varied also between years and study sites, the total amount of nonlocal viable pollen in the air was 2.3% from all detected viable pollen grains. The effect of pollen origin on seeds siring ability was studied with artificial pollination experiments. Pollen genotypes originating from southern Finland sired 76% and 48 % of the analysed seeds in competition studies where both pollen origin were introduced simultaneously into the female strobili. We examined the importance of arrival order of pollen grains in to the strobili in a study where pollen genotypes of different origin were introduced in two hours interval. Northern genotypes sired 76% of the analysed seeds when it was injected first, but in the "southern first" experiment both pollen types sired equal amount of seeds. The first pollen grain in the pollen chamber do not always fertilizes the ovum, instead there likely is more complex way of competition between pollen grains. To examine chemically mediated pollen-pollen interactions we conducted in vitro germination experiment where different pollen genotypes had chemical but not physical contact. Both positive and negative effects of interactions were found. We found highly negative effects in germinability of northern pollen grains when they were germinating with southern pollen, and increase in the germinability of southern pollen. There were no variation in the size of the dry pollen grains between pollen origins, and minor variation between different genotypes. After hydration and germination northern pollen grains were larger than southern pollen. Pollen genotypes having high hydration rates had low germinability and tube growth rate, however, germinated pollen grains were larger in size than nongerminated. This supports the suggestion that the early germination and growth of pollen tube is dependent on pollen storage materialsand less dependent on water intake and hydration. Long distance pollen movements and good competition ability of southern pollen makes gene flow possible, although rising temperature and timing of pollen movements may affect pollen competition and the amount of gene flow.

Asymmetrical flow field-flow fractionation in the study of water-soluble macromolecules

Asymmetrical flow field-flow fractionation (AsFlFFF) was constructed, and its applicability to industrial, biochemical, and pharmaceutical applications was studied. The effect of several parameters, such as pH, ionic strength, temperature and the reactants mixing ratios on the particle sizes, molar masses, and the formation of aggregates of macromolecules was determined by AsFlFFF. In the case of industrial application AsFlFFF proved to be a valuable tool in the characterization of the hydrodynamic particle sizes, molar masses and phase transition behavior of various poly(N-isopropylacrylamide) (PNIPAM) polymers as a function of viscosity and phase transition temperatures. The effect of sodium chloride salt and the molar ratio of cationic and anionic polyelectrolytes on the hydrodynamic particle sizes of poly (methacryloxyethyl trimethylammonium chloride) and poly (ethylene oxide)-block-poly (sodium methacrylate) and their complexes were studied. The particle sizes of PNIPAM polymers, and polyelectrolyte complexes measured by AsFlFFF were in agreement with those obtained by dynamic light scattering. The molar masses of PNIPAM polymers obtained by AsFlFFF and size exclusion chromatography agreed also well. In addition, AsFlFFF proved to be a practical technique in thermo responsive behavior studies of polymers at temperatures up to about 50 oC. The suitability of AsFlFFF for biological, biomedical, and pharmaceutical applications was proved, upon studying the lipid-protein/peptide interactions, and the stability of liposomes at different temperatures. AsFlFFF was applied to the studies on the hydrophobic and electrostatic interactions between cytochrome c (a basic peripheral protein) and anionic lipid, and oleic acid, and sodium dodecyl sulphate surfactant. A miniaturized AsFlFFF constructed in this study was exploited in the elucidation of the effect of copper (II), pH, ionic strength, and vortexing on the particle sizes of low-density lipoproteins.