<p>Insulin sensitivity is related to the fatty acid profile of skeletal muscle. The aim of this thesis was to investigate whether physical activity and dietary fat quality, independent of each other, influence the fatty acid composition of the skeletal muscle lipids. In an intervention study where middle-aged men were exercising for six weeks, and in a cross-sectional study comparing sedentary with endurance trained young men, it was demonstrated that the fatty acid composition of skeletal muscle lipids differed between physical active and inactive men. In brief, a lower proportion of palmitic acid (16:0) and total n-6 polyunsaturated fatty acids (PUFA) and a higher proportion of stearic (18:0) and oleic acid (18:1n-9) and total n-3 PUFA in the muscle phospholipids were associated with physical activity, despite similar fatty acid composition of the diet. In the second study, that included a larger training volume, differences in the fatty acid profile were also found in the skeletal muscle triglycerides. </p><p>In contrast, after short-term supra-maximal exercise we found no significant changes in the proportion of the fatty acids in skeletal muscle. </p><p>Furthermore, after a treatment period of three months, with diets with various dietary fat quality, the proportions of saturated fatty acids (14:0, 15:0 and 17:0) were higher and the proportion of 18:1 n-9 lower in subjects with a high intake of saturated fatty acids compared with subjects with a high intake of monounsaturated fatty acids. In addition subjects given n-3 supplementation had a higher proportion of total n-3 PUFA and lower n-6 PUFA in the skeletal muscle phospholipids than controls. Differences similar to those observed in the phospholipids were found in the triglycerides. </p><p>In summary, these results suggest that regular aerobic physical activity and dietary fat quality influence the fatty acid composition of the skeletal muscle lipids, which may affect insulin sensitivity and glucose homeostasis. </p>

<p>Skeletal muscle accounts for the largest part of insulin-mediated glucose uptake. Insulin resistance (IR) is the main component of insulin resistance syndrome (IRS) and is an essential cause of a number of cardiovascular risk factors. This thesis investigates the relationships between muscle morphological characteristics and IRS because skeletal muscle is responsible for the majority of glucose uptake.</p><p>In this population-based sample of 70-year-old men, higher proportion of type I fibers as well as higher capillarization were related to higher insulin sensitivity and higher self-reported physical activity, which were related to a lower prevalence of type IIB fibers. Serum triglycerides, HDL cholesterol and plasminogen activator inhibitor-1 (PAI-1) activity were significantly related to fiber distribution and muscle capillarization and muscle morphology, in part, explained the association between these metabolic risk factors with physical activity level. BMI, glucose intolerance, PAI-1 activity, serum FFA concentration, proportion of type IIB fibers, HDL cholesterol level, drug treatment, physical activity level, and W/H ratio together explained 55% of the variation in the insulin sensitivity index. In addition, almost a twofold improvement of the correlations was seen after correcting for intraindividual variation. Glucose tolerant hypertensive subjects showed a lower capillary supply when compared to controls. Capillary density was negatively correlated to the increase in mean arterial pressure over two decades as well as to supine heart rate 20 years before. Interestingly, supine heart rate showed an independent inverse association to the percentage of type I fibers and a positive correlation to the percentage of type IIB muscle fibers. Capillary density and elevated serum free fatty (FFA) acid values were inversely associated with insulin-mediated blood flow and thus to endothelial dysfunction, which has been linked to IR. In fact, capillary density and serum FFA level together explained 71% of the variation in insulin-mediated leg blood flow changes.</p><p>In conclusion, these population-based findings support the observations that muscle morphological features and insulin sensitivity are related to each other. Muscle morphology might explain some of the beneficial impact of physical activity on the components of IRS. Accordingly, we suggest that alterations in muscle morphology should be considered as an essential part of the IRS.</p>

<p>The glycaemic responses to various carbohydrate-rich foods are partly dependent on the rate at which the carbohydrate is digested and absorbed. The glycaemic index (GI) is a way of ranking foods according to their glycaemic response and is recommended as a useful tool in identifying starch-rich foods that give the most favourable glycaemic response. This investigation was undertaken to determine whether carbohydrate-rich foods with a low GI and a high content of dietary fibre (DF) could have beneficial metabolic effects in the insulin resistance syndrome. This question was addressed both in single-meal studies and in randomised controlled clinical trials. Starch-rich foods with low GI values incorporated into composite meals resulted in lower postprandial responses of both glucose and insulin than foods with a high GI in meals with an identical macronutrient and DF composition, in subjects with type 2 diabetes. After three weeks on a diet including low GI starchy foods metabolic profile was improved in subjects with type 2 diabetes, compared with a corresponding high GI diet. The glucose and insulin responses throughout the day were lower, the total and low density lipoprotein cholesterol was decreased, and the fibrinolytic activity was normalised. In subjects with impaired insulin sensitivity and diabetes low GI foods rich in soluble DF for breakfast gave a more favourable metabolic profile, with smaller glucose fluctuations from baseline during the day, than a breakfast with high GI foods low in DF. A low GI breakfast high in DF also resulted in lower responses of insulin and C-peptide after breakfast and a lower triacylglycerol response after a standardised lunch. However, none of the tested breakfasts improved the glucose and insulin responses after lunch. Similar results were obtained in obese subjects after including a breakfast with a low GI high in soluble DF for a period of four weeks in comparison with a breakfast with a high GI and low content of DF.</p><p>These results support the therapeutic potential of a diet with a low GI in the treatment of diabetes and also in the treatment of several of the metabolic disturbances related to the insulin resistance syndrome.</p>

<p>In this thesis, the importance of the growth hormone (GH)/insulin-like growth factor (IGF) system and sex steroids for male bone metabolism has been investigated, and the effects of continuous low dose GH replacement in GH deficient (GHD) adults. In a population-based sample of men, positive correlations were found between bone mineral density (BMD) and IGF-I, IGF-II, IGF binding protein (IGFBP)-3 and the testosterone/sex hormone binding globulin (SHBG) ratio. Serum IGFBP-3 and testosterone levels and weight accounted for 34% to 48% of the variation in BMD at different sites. Compared to healthy age matched controls, men with idiopathic osteoporosis had lower estradiol/SHBG ratio and higher SHBG levels. There were no differences between the groups in serum levels of IGF-I, IGFBP-3, 24 hour cumulated GH secretion or peak GH secretion. In the patients, there was a positive correlation between the estradiol/SHBG ratio and BMD in femoral neck. Treatment of patients and controls with GH 0.8 mg/day for one week resulted in similar increases in serum markers for bone turnover in both groups. Several positive correlations between indices of GH secretion and markers for bone turnover were found in the patients. Men with idiopathic osteoporosis were treated with GH, continuously (0.4 mg/day) or intermittently (0.8 mg/day for two weeks every third month), for two years followed by one year of follow-up. After two years, the BMD and bone mineral content in lumbar spine and total body and serum osteocalcin levels were increased in both groups. This increase was sustained one year post treatment. Treatment of GHD adults with a low fixed dose of GH (0.17 mg/day) for three months, resulted in increases in serum IGF-I and IGFBP-3 levels and lean body mass, and a reduction in fat mass and total and low-density lipoprotein cholesterol levels. These beneficial effects were accomplished without serious side effects. These findings indicate that: i) the sex hormone and GH/IGF systems are important in male bone metabolism, ii) a combination of subtle disturbances in these two systems could contribute to the development of male idiopathic osteoporosis, iii) GH treatment could be considered as a treatment option in this condition.</p>

<p>Prostasomes are extracellularly occurring organelles which are secreted in human semen by the prostate gland. Prostasomes have several known biological activities, but their physiological function is still unclear. In this thesis some new aspects were studied on the biological role of the prostasomes. </p><p>The motility-stimulatory effect of prostasomes on cryopreserved spermatozoa was further studied by supplementing the swim-up medium with seminal prostasomes, and with prostasomes purified from a PC-3 prostate cancer cell line (PC-3 prostasomes), on fresh spermatozoa. The recovery of motile spermatozoa after swim-up increased by 50% when the swim-up medium was supplemented with prostasomes. The PC-3 prostasomes bore a functional resemblance to seminal prostasomes as regards various expressions of sperm motility promotion. </p><p>Prostasomes proved to have potent antibacterial effects. The effects were not strictly confined to Bacillus megaterium since a few other bacteria were also sensitive. The high percentage of patients with anti-prostasome antibodies showed that prostasomes could be one of the major targets for antisperm antibodies (ASA). The results demonstrate that ASA in serum of infertile men and women recognise prostasomes as antigens, and that polyclonal antibodies raised against prostasomes agglutinate human spermatozoa. This suggests that prostasomes contribute at least partly to immunological infertility. Three types of prostasomes (seminal-, native- and metastasis-derived prostasomes) demonstrated similarities regarding a high cholesterol/phospholipid ratio and some marker enzymes. The conclusion is that prostasomes have a common and exclusive prostatic origin in man and that they are internalised in storage vesicles of the secretory cells and released in toto by an ordinary exocytotic event.</p>

<p>The aim was to describe and explore the food-related work and eating habits of older community-dwelling women, with Parkinson’s disease, rheumatoid arthritis or stroke or without these diseases. The major focus is on health perceptions, eating habits and meal support. A theoretical framework based on cultural and health theories was adopted. A total of 91 women between 64 and 88 years were visited in their homes, a food survey was performed consisting of a 24h recall and an estimated three-day food diary was introduced. Seventy-two of the women also took part in qualitative interviews with an ethnographic approach. Approximately one week later, another 24h recall was carried out at a second visit, or for the non-disabled women by telephone. The analyses revealed that many women were influenced by the prevailing health message and tried to eat a healthy diet. It was also important to them to enjoy their preferred foods, but this gave some women a bad conscience, while others perceived their usual foods as wholesome to eat. Health promotion for older women needs to incorporate the women’s own cultural context, their perceptions of food-related health, and their wish to adhere to their usual habits. Women with disease, frailty and who had become alone reported simplified food-related work and poor eating habits. However, management of these duties was highly valued, and women strove to cook by themselves as long as possible when disability became a threat. This resulted in a trend towards less nourishing cooked meals for women with disabilities. Thus, many women with these diseases living at home need support with their meals. This has to be planned in collaboration with the woman and build on her cultural values. The help must be performed with respect for the woman’s sense of order, be given sufficient time, and acknowledge her self-determination.</p>

<p>The aim of this thesis was to examine different approaches to support the self-care of persons with Type 2 diabetes, with special reference to practical, social, and sexual aspects of women's self-management. The methods to elucidate this comprised: evaluating a new model for diabetes patient education; designing a model to analyse the role of social networks in women's diabetes; conducting individual and focus group interviews for deeper understanding of the social and sexual aspects of diabetes; and collecting questionnaire data as a complement to the above.</p><p>The experience-based educational program led by pharmacists was found to improve participants' subjective control over diabetes and to provide important emotional support and encouragement to continue self-care. Metabolic control as measured by HbA_1c temporarily improved. The social network model elucidated potential mechanism leading to conflict of disease and social demands in women's diabetes. Qualitative analysis of the focus group interviews pointed to the role of guilt, shame, and social taboo in connection with the women's diabetes and sexuality.</p><p>Borderland is the metaphor I have chosen to describe the space between the traditional health care system and the everyday self-care of people with chronic disease. Using Borderland as a framework, a future model for diabetes management, anchored in our own and other's findings, is outlined and the concept of "Disease Manager Role" is introduced. The vision of a self-care support center in Borderland addresses such issues as accessibility, continuity, equitable provider-user relations, shared care plans, and strengthening social support.</p>

<p>Primary Sjögren's syndrome (pSS) is a chronic inflammatory connective tissue disease of unknown etiology. The disease primarily involves salivary and lacrimal glands which results in oral and ocular dryness (sicca symptoms). A wide spectrum of extraglandular features from various organs may be seen. </p><p>In this thesis, the frequency of psychiatric symptoms in women with primary Sjögren's syndrome was studied and an attempt was made to assess how these symptoms might influence their well being and quality of life. The main finding was that the women with pSS suffered significantly more often from symptoms of anxiety and depression when compared with age matched, healthy females and female patients with rheumatoid arthritis. The physical and mental well-being of the patients with pSS was significantly reduced compared to patient controls. </p><p>The possible link of psychiatric symptoms to the altered function of the hypothalamic-pituitary-gonadal axis and adrenal androgen secretion was elucidated. Women with pSS have intact cortisol synthesis but reduced serum concentrations of dehydroepiandrosterone sulphate (DHEA-S) (p<0.05) and an increased cortisol/DHEA-S ratio (p<0.05), compared to healthy controls. These findings may reflect a constitutional or disease-meditated influence on adrenal steroid synthesis. Positive correlation was found between DHEA-S serum levels and quality of sexual life (p<0.01) and mental well-being (p<0.01) in women with pSS. </p>

<p>Drugs and other foreign compounds must often be metabolised before they can be excreted from the body. One enzyme system that is responsible for this is the cytochrome P450 gene family (CYP). In this thesis, new sensitive molecular techniques have been used to study the human gene expression of some CYP enzymes, as well as the P-glycoprotein transporter (P-gp). The aim was to evaluate whether tissues other than the liver, e.g. the blood, could be used to assess an individual's drug metabolic capacity. Another aim was to investigate the gene expression in relation to the liver transplant process and a third aim was to evaluate the expression in gastrointestinal mucosa in both normal and inflamed mucosa.</p><p>We evaluated the CYP gene expression in paired specimens of liver and blood but found no correlation in the expression patterns of these two tissues. Instead, we found the opposite pattern, where, for example, CYP1B1 had the highest expression in the blood but the lowest in the liver and CYP2E1 was the enzyme with the highest expression in the liver. In an investigation of the expression of four different CYP enzymes and P-gp in liver transplants before and during the first year after transplantation, we found that the levels of all the CYP enzymes but not P-gp increased with time. We also found that the expression of CYP3A4 was inversely related to the normalised plasma levels of the immunosuppressive drugs cyclosporine and tacrolimus.</p><p>In the gastrointestinal tract, CYP2E1 was the enzyme with the highest mRNA expression compared with CYP3A4, CYP3A5 and the transporter P-gp. CYP3A4 has its highest expression in the duodenum compared with the expression in the stomach and the colon. CYP3A5 is expressed at a higher level than CYP3A4 in the colon. P-gp expression levels increase through the gastrointestinal tract to the left colon. Gene expression levels of CYP2E1 and CYP3A4 decrease in severely inflamed rectal mucosa. </p><p>In conclusion, this is a sensitive method for studying gene activity in a clinical situation, even though at this point we are not able to use blood or gastrointestinal mucosa as “surrogate” tissue to estimate an individual’s drug metabolic capacity. The studies in liver transplants and gastrointestinal mucosa are unique in that the gene expression is investigated during a clinical course of events.</p>

<p>The objectives of this case-control study, investigating 51 in-patient women with acute pelvic inflammatory disease (PID) and 50 healthy women attending for routine gynecological check-up, were to investigate the background and reproductive history of women, who are considered at low risk of sexually transmitted infection presenting with PID, to examine whether intrauterine device (IUD) use <i>per se</i> and long use affects the microbiology and clinical course of the disease, to identify risk factors for PID and to examine whether IUD use is an independent risk factor for PID.</p><p>The most striking difference regarding the background and reproductive history between women with PID and healthy women over age 25 were related to socio-demographic factors and not to common risk factors for PID.</p><p>There was little difference between healthy women and women with current PID with regard to single microbes. The finding of combinations of several anaerobic or aerobic/anaerobic microbes appeared to be associated with PID, particularly in women over 35. The pathogenesis of non-sexually transmitted PID appears to be associated with a synergistic effect between several pathogens, possibly facilitated by the presence of an IUD.</p><p>IUD use <i>per se</i> was associated with an increased risk of PID in women 35 and older. There was an association between IUD use and complicated PID in women over 35, which was possibly influenced by long-term IUD use. Age over 35 and IUD use, independently of each other, were associated with an increased risk of failed conservative treatment, necessitating surgery in patients with PID.</p><p>An observational study showed that Latvian obstetrician-gynecologists participate actively in contraceptive counseling and are very experienced with regard to IUD use. Physicians’ attitudes and perceptions towards IUD are generally positive and their clinical considerations are in good agreement with that of doctors in other countries. Antibiotics are widely used around IUD insertion by doctors, possibly driven by a liberal attitude towards IUD use in women with a potential risk of STI. The study could identify some possible gaps in the theoretical knowledge about the IUD and other methods.</p>