| 31. |
- Andersson, Agneta
(författare)
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Fatty Acid Composition in Skeletal Muscle : Influence of Physical Activity and Dietary Fat Quality
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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. In contrast, after short-term supra-maximal exercise we found no significant changes in the proportion of the fatty acids in skeletal muscle. 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. 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.
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| 32. |
- Andersson, Annika K., 1974-
(författare)
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Role of Inducible Nitric Oxide Synthase and Melatonin in Regulation of β-cell Sensitivity to Cytokines
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The mechanisms of β-cell destruction leading to type 1 diabetes are complex and not yet fully understood, but infiltration of the islets of Langerhans by autoreactive immune cells is believed to be important. Activated macrophages and T-cells may then secrete cytokines and free radicals, which could selectively damage the β-cells. Among the cytokines, IL-1β, IFN-γ and TNF-α can induce expression of inducible nitric synthase (iNOS) and cyclooxygenase-2. Subsequent nitric oxide (NO) and prostaglandin E2 (PGE2) formation may impair islet function.In the present study, the ability of melatonin (an antioxidative and immunoregulatory hormone) to protect against β-cell damage induced by streptozotocin (STZ; a diabetogenic and free radical generating substance) or IL-1β exposure was examined. In vitro, melatonin counteracted STZ- but not IL-1β-induced islet suppression, indicating that the protective effect of melatonin is related to interference with free radical generation and DNA damage, rather than NO synthesis. In vivo, non-immune mediated diabetes induced by a single dose of STZ was prevented by melatonin.Furthermore, the effects of proinflammatory cytokines were examined in islets obtained from mice with a targeted deletion of the iNOS gene (iNOS -/- mice) and wild-type controls. The in vitro data obtained show that exposure to IL-1β or (IL-1β + IFN-γ) induce disturbances in the insulin secretory pathway, which were independent of NO or PGE2 production and cell death. Initially after addition, in particular IL-1β seems to be stimulatory for the insulin secretory machinery of iNOS –/- islets, whereas IL-1β acts inhibitory after a prolonged period. Separate experiments suggest that the stimulatory effect of IL-1β involves an increased gene expression of phospholipase D1a/b. In addition, the formation of new insulin molecules appears to be affected, since IL-1β and (IL-1β + IFN-γ) suppressed mRNA expression of both insulin convertase enzymes and insulin itself.
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| 33. |
- Andersson, Charlotte
(författare)
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Towards Pharmacological Treatment of Cystic Fibrosis
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- S-nitrosogluthatione is an endogenous substance, present at decreased levels in the lungs of CF patients and was recently found to induce mature CFTR in airway epithelial CF cell lines. We show that S-nitrosoglutathione in physiological concentrations increases the presence of ΔF508 CFTR in the cell membrane and induces cAMP dependent chloride transport in cystic fibrosis airway epithelial cells. The properties of S-nitrosoglutathione include other potential benefits for the CF patient and make this agent an interesting candidate for pharmacological treatment of CF that needs to be further evaluated.Genistein was found to increase the chloride efflux in both normal and ΔF508 cells without stimulation of cAMP elevating agents and without prior treatment with phenylbutyrate. Genistein, in concentrations close to those that can be detected in plasma after a high soy diet, could induce chloride efflux in cells with the ΔF508 CFTR mutation and its possible use in the treatment of CF should therefore be further investigated.Studies on nasal epithelial cells from CF patients showed cAMP dependent chloride efflux in some of the patients with severe genotypes. This may complicate in vitro evaluation of clinical treatment of these patients. The presence of cAMP dependent chloride transport did not necessarily lead to a milder phenotype. Other factors than CFTR may influence the clinical development of the disease.Cystic fibrosis (CF) is the most common monogenetic disease among Caucasians. A defective cAMP regulated chloride channel (cystic fibrosis transmembrane conductance regulator, CFTR) in epithelial cells leads to viscous mucus, bacterial infections, inflammation and tissue damage in the lungs that cause death in 95% of the cystic fibrosis patients. There is no cure for the disease although existing treatment has dramatically prolonged the life expectancy. The aim of this thesis was to study pharmacological agents for their ability to restore the cellular deficiency in CF airway epithelial cells. X-ray microanalysis, MQAE fluorescence and immunocytochemistry were used to evaluate the effects.
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| 34. |
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| 35. |
- Andersson, Gerhard
(författare)
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Clinical Aspects of Tinnitus- Course, Cognition, PET, and the Internet
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this thesis was to develop novel ways to study tinnitus, to investigate the course of tinnitus, and to study the effects of cognitive-behaviour therapy on tinnitus related distress. Data from 377 tinnitus patients were collected.A group of 216 patients completed audiological measures and were assessed in a structured interview. The Klockhoff and Lindblom's grading system was used and its inter-rater reliability assessed in a subsample showing a high degree of correspondence. A discriminant analysis showed that a substantial proportion of patients could be correctly classified into grade II or III, by measures of pitch, minimal masking level of tinnitus, avoidance of situations because of tinnitus, and tolerance in relation to onset.Using tests developed in cognitive psychology, it was found that tinnitus patients had impaired performance. There was no evidence for an attentional bias towards tinnitus related words using a computerized emotional Stroop task, but masking sounds of an "on-and-off" character were more disruptive than constant masking when patients performed the digit-symbol test. It is suggested that tinnitus distress may be increased by the 'changing-state' character of the tinnitus signal, or alternatively by intermittent masking sounds.In a case-study a patient received an i.v. injection of lidocaine while Positron Emission Tomograpy was conducted. The brain activity associated with tinnitus included the left primary, secondary and integrative auditory brain areas, as well as right paralimbic areas related to negative feelings. The precuneus (Brodmann area 7) might be a brain area involved in the aversiveness associated with tinnitus.Using a tinnitus questionnaire as the dependent measure it was found that tinnitus maskability at admission predicted distress at follow-up for an average of five years following admission. Some improvement in tinnitus occurred over time, but this was more evident in patients who had received a cognitive-behavioural treatment program.The effect of an Internet based cognitive-behavioural self-help treatment program for tinnitus was investigated showing a high dropout rate, but with positive results in that the treated patients improved.
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| 36. |
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| 37. |
- Andersson, Jonas
(författare)
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Complement Activation Triggered by Biomaterial Surfaces : Mechanisms and Regulation
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Today there are a vast number of medical devices in temporary or permanent contact with human tissues. Blood-biomaterial contact is known to trigger the complement system and results in generation of fluid phase anaphylatoxins C3a and C5a, and surface-bound C3b and iC3b. All these products together are able to attract and activate leukocytes and trigger release of inflammatory mediators leading to a systemic inflammation indirectly causing hemostatic problems and even organ failure. The aim of this study was to identify how complement is triggered on a biomaterial surface and to find ways to regulate this activation.The finding that complement activation on biomaterials can be divided into initiation and amplification will facilitate regulation of complement activation biomaterial surfaces. This concept is also compatible with the two techniques to regulate complement activation on a surface.
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| 38. |
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| 39. |
- Andersson, Karl, 1972-
(författare)
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Characterization of Biomolecular Interactions Using a Multivariate Approach
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents a novel bioinformatic methodology denoted the bio-chemometric approach. The methodology is designed for generation of detailed descriptions and predictions of biomolecular interactions. It is based on multivariate analysis of the sensitivity of a biomolecular interaction to multiple minor changes in the experimental conditions. In this work, either the chemical environment where the interaction takes place, or the molecular structure of one of the interacting molecules, was varied. The sensitivity of the interaction to the performed variations was presented as a vector called the sensitivity fingerprint. The bio-chemometric approach was tested on several biomolecular interactions. Useful descriptions of the interactions were obtained by measuring binding kinetics for each interaction in 12-20 different buffers and correlating buffer composition to binding kinetics. The obtained chemical sensitivity fingerprints were reproducible, significantly different and showed a weak correlation to binding site properties for the tested interactions. The results indicate that the fingerprints contained useful information about the binding site. The predictive ability of the bio-chemometric approach was tested on two different biomolecular interactions where one of the binding partners was slightly modified into multiple analogues by amino acid exchanges. In one example, interactions of 18 peptide analogues with an antibody gave data that could be used for accurate prediction of the dissociation rates of novel analogues. Reliable predictions of binding kinetics and affinity were also obtained for single domain camel antibody analogues binding to a protein antigen. By using the three-dimensional structure of camel antibodies and data obtained using the bio-chemometric approach, even the importance of non-exchanged amino acids for the binding could be estimated. The bio-chemometric approach can potentially improve the development of peptides and proteins for therapeutic and diagnostic use. It is suggested to be valid for general use in biochemistry.
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| 40. |
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