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. 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.

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.

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. 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. 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.

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.

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. 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. 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. 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.

The use of a new, more sensitive immunoassay for growth hormone (GH) revealed that the serum levels in men were lower than expected in sera drawn ambulatory in the morning after an overnight fast and that the gender difference was more than 10 times greater than reported. These observations led to a more thorough study on the impact of gender and sex steroids on the levels of GH and other hormones in ambulatory morning samples and over a 24-hour period. Furthermore, the impact of gender was studied in GH deficient (GHD) patients and healthy young adults treated with GH, and in patients with acromegaly treated with octreotide. An 80-fold gender difference in the morning GH levels was observed in young individuals as a reaction to ambulation, with decreased levels in men and increased in women. Oral contraceptives (OCs) given to women further increased the morning GH levels. During the day, higher outputs of epinephrine and lower levels of GH were seen in the men, while no gender differences were seen at night. The gender difference in morning GH levels decreased with age due to opposite changes in men and women. Administration of 17β-estradiol (E2) via subcutaneous implants in postmenopausal women, which increased the E2-concentrations to luteal phase levels, had no effect on the morning GH levels, indicating that the different reactions to ambulation do not appear to result from a direct sex steroid effect alone. Short-term administration of GH to young, healthy adults resulted in larger effects on insulin-like growth factor I (IGF-I) and other key metabolic parameters in men than in women. The smallest response was noted in women taking OCs. The clinical studies involving long-term GH treatment of patients with GHD demonstrate a gender difference in GH responsiveness, with women being less sensitive than men, a fact which should have a therapeutic impact in patients with GH disorders. A further gender difference of therapeutic importance was observed in men and women with acromegaly. Long-term treatment with a slow-release formulation of octreotide resulted in higher IGF-I levels in the men, despite equal doses of the drug and similar levels of GH.

Palmoplantar pustulosis (PPP) is a chronic disease of unknown pathogenesis. Most of the patients were smokers. High prevalence of a number of autoimmune diseases was observed among the patients (thyroid disease 14%, gluten intolerance 8%, diabetes type 1 3%). Eosinophils and neutrophils were found in large numbers in the pustules. Massive infiltrates of lymphocytes and mast cells in the dermis below the pustule and an abnormal acrosyringial pattern indicate that the acrosyringium is the target for the inflammation. Immunofluorescence (IF) revealed decreased innervation of the sweat gland, outward migration of substance P-positive granulocytes in the acrosyringium and an increased number of contacts between mast cells and nerve fibres in the dermis. Distributions of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were studied, since they regulate the level of acetylcholine, the main inducer of sweating. The most intense AChE-like immunoreactivity (LI) was observed in the acrosyringium in the lowest part of the stratum corneum, corresponding to the site of the pustule in PPP. ChAT-LI in granulocytes and AChE-LI in mast cells were demonstrated, which may have implications for inflammatory processes in general. Nicotinic acetylcholine receptors (nAChR) are activated by acetylcholine but also by nicotine. Immunohistochemstry of α-3 and α-7 subtypes of the nAChRs showed that the nAChR expression in healthy skin was influenced by smoking. A highly abnormal α-7 nAChR distribution in PPP skin was observed. The levels of nAChR antibodies were elevated in 42% of the PPP sera, and 68% of these sera gave specific endothelial IF in the papillary dermis in skin from non-smokers. Positive IF in the acrosyringium was also noted in skin from smokers. Conclusions: Smoking seems to induce up-regulation of an antigen in palmar skin. The results indicate that PPP is an autoimmune disease and that nicotine might have a role in the onset of the inflammation.

Chronic graft dysfunction (CGD) is an important post-transplant complication. CGD can be considered as an impaired repair process, which ultimately leads to the loss of graft function.To study non-immunological factors contributing to the development of CGD in kidney grafts we used in vitro and in vivo models, and clinical studies. We studied the actions of hyperlipidemia in vitro. LDL induced increased expression of TGF-β1 and TGF-β receptors type I and type II. Smad2 phosphorylation could be induced by conditioned medium from mesangial cells incubated with LDL. The effects of Fluvastatin and AT1 receptor blocker Candesartan cilexetil on aortic graft arteriosclerosis in the rat were evaluated. Fluvastatin neither alone nor in combination with Cyclosporine A affected allograft remodelling, but reduced neointima formation in isografts. Candesartan cilexetil treatment reduced graft arteriosclerosis. The effect is explained by the reduction of TGF-β1 expression. We investigated the effects of Carvedilol in patients with CGD. Carvedilol failed to alter the CGD progression despite the efficient control of blood pressure, and a beneficial effect on lipid pattern and oxidation. Close control of CyA blood levels is recommended due to interaction between CyA and Carvedilol. Measurement of Ab-oxLDL in kidney graft recipients demonstrated that these patients had lower Ab-oxLDL levels as compared with the control group. Decreased Ab-oxLDL levels were associated with graft loss due to acute rejection and with ischemic heart disease. In this thesis we have addressed several important complex issues, which are interconnected: (1) development of chronic graft dysfunction (2) lipoproteins and their role in inducing pathological conditions like atherosclerosis and graft damage, (3) oxidation, (4) TGF-β and its' role in different pathological conditions, including renal and vascular damage.

The principal aim has been to investigate the contemporary role and importance of edible wild plants in the diets of women in different agro-ecological regions of Vietnam. Field studies were undertaken in four villages in the Mekong Delta (MD) and the Central Highlands (CH) in 1995-1999. Data collection included rapid appraisal techniques, botanical identification, dietary assessments (7-day food frequency recall), anthropometry, blood sampling (haemoglobin, serum ferritin, serum retinol and C-reactive protein) and analysis of vegetable samples (dry matter, selected minerals and vitamins, tannins and phytic acid). A food variety analysis was used to test the adequacy of diets. The uses of over 90 wild plant species were documented, many with multiple functions as foods, medicines and livestock feeds. In the dietary assessment 29 species were reported. Most women used a combination of home produced, commercial and wild vegetables. A high 72 and 43% respectively of the vegetables consumed in the MD and CH sites were gathered (rainy season). They contributed significantly to micronutrient intakes, especially vitamin A, calcium, vitamin C and folate. They added considerably to food diversity and women with the most diverse diets had relatively adequate nutrient intakes. The species used and importance of wild plants varied considerably with region, season and ethnicity. The main conclusions are that edible wild plants continue to make important contributions to the nutrient intakes of women. If this is neglected in diet assessments our understanding of the overall dietary adequacy may be misinterpreted and much valuable knowledge of traditional food diversification may be lost. A food variety analysis can be a useful tool in identifying groups with inadequate diets. The dual role of many species as dietary components and in preventive health care deserves greater attention.

Swedish health care is currently facing problems, such as lack of financial resources, staff shortage and dissatisfaction among patients and professionals. Patients’ dissatisfaction was the point of departure for the present study, and one approach dealing with this problem was investigated. It was hypothesised that a patient-centred perspective could offer a possible solution. The aim of the study was to explore health care professionals’ and medical students’ understanding of their professional role and the patient encounter. A further goal was to determine whether these understandings could be developed by educational interventions. Students and professionals have been either interviewed or responded to a survey about their professional role and the patient encounter. Qualitative analysis was used. One group- and one individualised intervention were carried out. The participants’ understandings of their professional role were taken as the starting point for learning. The results showed that a minority of medical students and professionals in diabetes care had incorporated a patient-centred perspective. Nurses in telephone advisory services recognised the patients’ needs, but experienced conflicting demands of being both carer and gatekeeper. A non-optimal match between patients’ needs and what professionals understand as their role could cause some of the problems. Competence development could be achieved by taking the participants understanding of the professionals’ role and of the patient encounter as a starting point for reflection. The results have implications for changes in organisation and education in health care, to optimise outcomes of care. Time for reflection, mentoring and professional development is needed.