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  • 1.
    Akanda, Nesar
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Voltage-dependent anion channels (VDAC) in the plasma membrane induce apoptosis2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Apoptosis, or programmed cell death, is essential for proper development and functioning of the body systems. During development, apoptosis plays a central role to sculpt the embryo, and in adults, to maintain tissue homeostasis by eliminating redundant, damaged or effete cells. Therefore, a tight regulation of this process is essential. Cell shrinkage associated efflux of K+ and Cl through plasma membrane ion channels is an early event of apoptosis. However, little is known about these fluxes. The aim of this thesis was to investigate ion channels in the plasma membrane of neurons undergoing apoptosis. We studied differentiated (the mouse hippocampal cell line HT22, the human neuroblastoma cell line SK-N-MC, and rat primary hippocampal neurons) and undifferentiated (rat primary cortical neural stem cells cNSCs) cells with the patch-clamp technique. All cell types displayed a low electrical activity under control conditions. However, during apoptosis in differentiated neurons, we found an activation of a voltage-dependent anion channel. The conductance of the channel is 400 pS, the voltage dependence of the opening is bell shaped with respect to membrane voltage with a maximum open probability at 0 mV, and the Cl to cation selectivity is >5:1. These biophysical properties remind about the voltage-dependent anion channel normally found in the outer mitochondrial membrane (VDACmt). Hence, we call our apoptosis-inducing plasma membrane channel VDACpl. The molecular identity of the channel was corroborated with the specific labelling of different anti-VDAC antibodies. Block of this channel either with antibodies or with sucrose prevented apoptosis, suggesting a critical role for VDACpl in the apoptotic process. VDACpl is a NADH (-ferricyanide) reductase in control cells. We found that the enzymatic activity is altered while the VDACpl channel is activated during apoptosis. Surprisingly, in cNSCs we did not find any activation of VDACpl, no VDACpl-specific labelling, no enzymatic activity, and no prevention of apoptosis with VDACpl-blocking strategies. Instead, we found an activation of a voltage-independent 37 pS ion channel, and that the Cl channel blocker DIDS prevented apoptosis in cNSCs. Our finding that activation of VDACpl is critical for apoptosis in differentiated neurons hopefully can lead to new strategies in the treatment of several diseases related to apoptosis.

  • 2.
    Andersson, Anna
    Linköping University, Faculty of Health Sciences, Engelska: Faculty of Health Sciences, Medical Programme.
    Adjuvant and Down-Staging Treatment with Imatinib in Gastrointestinal Stromal Tumours2008Independent thesis Advanced level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: GISTs are gastrointestinal mesenchymal tumours that express the type III receptor tyrosine kinase KIT. The KIT proto-oncogene encodes the receptor KIT. Most GISTs have gain-of-function mutations in the KIT or PDGFRA gene. The tyrosine kinase is therefore continuously activated leading to ligand-independent dimerization. Imatinib mesylate (Glivec®) is considered to be the first-line palliative treatment. The activated form of the KIT receptor tyrosine kinase is inhibited by imatinib. The aim of the study was to compare the survival of patients treated with either adjuvant or down-staging imatinib with historic controls treated with radical surgery (R0) only.

    Methods: A historic control group was chosen from a population-based series from western Sweden (population 1.6 million) that matched the adjuvant (n=23) and down-staging (n=7) groups respectively. Mutation analysis was performed in all cases with bidirectional direct sequencing. The recurrence-free survival was calculated.

    Results: There was only one recurrence (4 %) in the adjuvant group, and no recurrences in the down-staging study group, compared to 32/48 patients (67 %) in the control group. Tumour size decreased in diameter from 20 cm to 11 cm with down-staging treatment.

    Conclusion: Adjuvant imatinib improves recurrence-free survival in R0 resected patients. Down-staging treatment with imatinib is recommended for patients with large tumours or metastases. The importance of mutation analysis was established.

  • 3.
    Andersson, Gunnel
    Örebro University, School of Health and Medical Sciences.
    Urinary incontinence: prevalence, treatment seeking behaviour, experiences, and perceptions among persons with and without urinary leakage2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overall aim of this thesis is to describe urinary incontinence (UI) from a population perspective and to describe experiences and perceptions of UI from an individual perspective. This includes assessing the prevalence of urinary incontinence as well as describing treatment seeking and experiences of living with UI. A secondary aim was to describe the perception of UI among cultures other than the Swedish mainstream, exemplified in this case by Syrian women living in Sweden. Both quantitative and qualitative methods were used, including questionnaires and interviews.

    Studies I and II were quantitative studies based on a population-based study. Together with a postal survey on general health and living conditions “Life & Health”, a questionnaire on urinary incontinence was sent out to 15 360 randomly-selected residents aged 18-79 in Orebro County, Sweden. In Study I, UI was found to affect 19%. The majority of the respondents experienced minor problems, and only 18% of those reporting UI wanted treatment. However, there was also a group who reported severe problems, but despite this 42% of them did not want treatment. Study II investigated why people with UI refrain from seeking care and treatment. It was found that the desire for treatment was regulated by the frequency of UI, being restricted from participating in various activities, the degree of inconvenience, and the type of UI.

    Studies III and IV were both qualitative interview studies, describing older women’s experiences of living with UI (Study III) and Syrian women’s perceptions of UI (Study IV). There were similarities between the results of these two studies; the women described UI as a normal and expected problem, and they knew that the district nurse could prescribe incontinence protections and that treatments existed. In both studies, the women expressed difficulties in making contact with the health care service, while the women who did not speak Swedish (Study IV) also had difficulties due to different communication problems.

    In conclusion, it is important that health care resources are optimized to identify and meet the needs of those who experience major problems with UI, and that there is awareness of the communication difficulties that can be present in meeting with people who speak other languages. However it is also important not to medicalize those who experience minor problems and who have the desire to manage on their own.

  • 4.
    Anderzén-Carlsson, Agneta
    Örebro University, Department of Clinical Medicine.
    Children with cancer: focusing on their fear and on how their fear is handled2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Various fears in children with cancer have previously been identified as a result of studying e.g. symptom experiences, distress and uncertainty within this population. Studies of the meaning the children give to their fear, as well as the handling of their fear seem to be sparse, however. Also, fear has not been an exclusive focus in previous studies. Professionals in clinical practice have pointed to the need for such research, which has prompted the present research work. The overall aim of this thesis was therefore twofold; firstly, the aim was to elucidate fear in children and adolescents with cancer in order to gain an understanding from the perspective of adolescents and parents. Secondly, it was to elucidate parents’ and professionals’ handling of the fear. This in order to gain a deeper understanding of what performances and manners the children and adolescents can face when being fearful. A qualitative descriptive design was adopted in the five included studies. The methods used in the data analysis were phenomenological hermeneutical method (studies I–III) and qualitative content analysis (studies IV–V).

    In study I six adolescent girls, aged 14–16 years, with experiences of various cancer diagnoses, but now declared fit, were interviewed. The results reveal that they experience their fear as embodied, which in the comprehensive understanding of the results was interpreted as a threat to their personal self, their whole existence. Their fear was seen as a holistic intertwined experience, including fear related to the physical body and to the social self. Also, existential fear was described. Their described experience was interpreted as suffering.

    Studies II and III share the same data. Fifteen parents of children at various ages with various cancer diagnoses were interviewed in focus groups about their experience of their child’s fear. In study II the result reveals how the parents experienced and understood their child’s fear. The fear was described as a multidimensional phenomenon, which was not always easy to identify. It was contrasted to feelings of unease and to absence of fear. In the comprehensive understanding the fear was interpreted as a suffering, as that was regarded to be what was the common meaning in the narratives. The suffering was interpreted as an ethical demand to the parents to take action. In study III the parents described their actions, i.e. they described how they dealt with the fear. Their actions were described as acting in the best interests of the child, which included striving to make the child feel secure and experience wellbeing, up to a certain point. However, after this point the parents used their parental authority to maintain the child’s physical health rather than trying to prevent or relieve the child’s fear. In the comprehensive understanding the parents’ handling of their child’s fear was interpreted as revealing mercy and as being synonymous with meeting the ethical demand put on them.

    In study IV ten experienced nurses and physicians were individually interviewed about how they handled fear in children with cancer. The result reveals that the existential issues were dealt with within the relationship with the child, on a sliding scale between closeness and distance, and that the fear related to medical procedures occurred on a continuum between support and lack of support. The various actions involved, and the manner in which these actions were performed, was described.

    In the observational study (study V) eleven parents and their children as well as eleven health professionals participated. They were observed at children’s routine visits at the outpatient clinic. The aim was to study the interactions related to fear. The result reveals that when children were fearful they expressed this both verbally and non-verbally. The parents’ and professionals’ actions and interactions in these situations were found to be characterized by recognition of the fear or lack of attention to the fear.

    The findings can contribute to a broadened knowledge on fear in children and adolescents with cancer. Awareness and understanding of the meaning adolescents give to their fear, and furthermore, of the parents’ experience and understanding of their child’s fear can provide tools for interacting with these groups. The findings on how fear is dealt with by the ones children have claimed as important sources for support, can give insights into what the child may face when being fearful. These insights can form the basis for individual, as well as collegial, reflections on what is done when children face fear, how fear is handled on an everyday basis and why it is handled in this way. Such reflections could lead to an ethical awareness of handling fear in children with cancer.

  • 5.
    Arvidsson, D.
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Nutr, SE-40530 Gothenburg, Sweden.
    Slinde, Frode
    University of Skövde, School of Life Sciences.
    Larsson, S.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med Respirat Med & Allergology, Gothenburg, Sweden.
    Hulthén, L.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Nutr, SE-40530 Gothenburg, Sweden.
    Energy cost of physical activities in children: Validation of SenseWear Armband2007In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 39, no 11, 2076-2084 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To examine the validity of SenseWear Pro2 Armband in assessing energy cost of physical activities in children, and to contribute with values of energy costs in an overview of physical activities in children. METHODS: Energy cost was assessed by SenseWear Pro2 Armband in 20 healthy children, 11-13 yr, while lying down resting, sitting playing games on mobile phone, stepping up and down on a step board, bicycling on a stationary bike, jumping on a trampoline, playing basketball, and walking/running on a treadmill at the speeds 2, 3, 4, 5, 6, 7, 8, and 10 km x h(-1). During these activities, energy cost was also assessed from VO2 and VCO2 measured by Oxycon Mobile portable metabolic system, which was used as criterion method. RESULTS: The difference in energy cost between SenseWear Pro2 Armband and Oxycon Mobile was -0.7 (0.5) (P < 0.001) for resting, -2.0 (0.9) (P < 0.001) for playing games on mobile phone, -6.6 (2.3) (P < 0.001) for stepping on the step board, -12.0 (3.7) (P < 0.001) for bicycling, -2.7 (11.9) (P = 0.34) for jumping on the trampoline, and -14.8 (6.4) kJ x min(-1) (P < 0.001) for playing basketball. The difference in energy cost between SenseWear Pro2 Armband and Oxycon Mobile for increasing treadmill speed was 1.3 (3.1) (P = 0.048), 0.1 (2.9) (P = 0.82), -1.2 (2.6) (P = 0.049), -1.6 (3.2) (P = 0.044), -3.1 (3.7) (P = 0.0013), -4.9 (3.7) (P < 0.001), -5.3 (3.7) (P < 0.001), and -11.1 (3.5) kJ x min(-1) (P < 0.001). CONCLUSIONS: SenseWear Pro2 Armband underestimated energy cost of most activities in this study, an underestimation that increased with increased physical activity intensity. A table of energy costs (MET values) of physical activities in children measured by indirect calorimetry is presented as an initiation of the creation of a compendium of physical activities in children

  • 6.
    Atikuzzaman, Mohammad
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Seminal Influence on the Oviduct: Mating and/or semen components induce gene expression changes in the pre-ovulatory functional sperm reservoir in poultry and pigs2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Internal fertilization occurs in birds and eutherian mammals. Foetal development, however, is either extra- respectively intra-corpore (egg vs uterus). In these animal classes, the female genital tract stores ejaculated spermatozoa into a restricted oviductal segment; the functional pre-ovulatory sperm reservoir, where they survive until ovulation/s occur. Paradoxically, this immunologically foreign sperm suspension in seminal fluid/plasma, often microbiologically contaminated, ought to be promptly eliminated by the female local immune defence which, instead, tolerates its presence. The female immune tolerance is presumably signalled via a biochemical interplay of spermatozoa, as well as the peptides and proteins of the extracellular seminal fluid, with female epithelial and immune cells. Such interplay can result in gene expression shifts in the sperm reservoir in relation to variations in fertility. To further aid our understanding of the underlying mechanisms, this thesis studied the proteome of the seminal fluid (using 2D SDS-PAGE and mass spectrometry) including cytokine content (using Luminex and/or ELISA) of healthy, sexually mature and fertile boars and cocks. As well, gene expression changes (using cDNA microarray) in the oviductal sperm reservoirs of sexually-mature females, mated or artificially infused with homologous sperm-free seminal fluid/plasma were studied. Pigs were of commercial, fertility-selected modern breeds (Landrace), while chicken belonged to the ancestor Red Junglefowl (RJF, low egg laying-capacity), a selected egg-layer White Leghorn (WL) and of their Advanced Intercross Line (AIL). Ejaculates were manually collected as single sample in cocks or as the sperm-rich fraction [SRF] and the post- SRF fraction in boars to harvest seminal fluid/plasma for proteome/cytokine and infusion-studies. Oviducts were retrieved for gene-expression analyses via microarray immediately post-mortem (chicken) or at surgery (pig), 24 h after mating or genital infusion. In pigs, the protein-rich seminal plasma showed the highest amounts of cytokines [interferon-γ, interferon gamma-induced protein 10 (IP-10/CXCL10), macrophage derived chemokine (MDC/CCL22), growth-regulated oncogene (GRO/CXCL1), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemo-attractant protein-1 (MCP-1/ CCL2), interleukin (IL)-6, IL-8/CXCL8, IL-10, IL-15, IL-17 and transforming growth factor (TGF)-β1-3) in the larger, protein-rich and sperm-poor post-SRF, indicating its main immune signalling influence. Chicken showed also a plethora of seminal fluid proteins with serum albumin and ovotransferrin being conserved through selection/evolution. However, they showed fewer cytokines than pigs, as the anti-inflammatory/immune-modulatory TGF-β2 or the pro-inflammatory CXCL10. The RJF contained fewer immune system process proteins and lacked TGF-β2 compared to WL and AIL, suggesting selection for increased fertility could be associated with higher expression of immune-regulating peptides/proteins. The oviductal sperm reservoir reacted in vivo to semen exposure. In chicken, mating significantly changed the expression of immune-modulatory and pH-regulatory genes in AIL. Moreover, modern fertile pigs (Landrace) and chicken (WL), albeit being taxonomically distant, shared gene functions for preservation of viable sperm in the oviduct. Mating or SP/SF-infusion were able to change the expression of comparable genes involved in pH-regulation (SLC16A2, SLC4A9, SLC13A1, SLC35F1, ATP8B3, ATP13A3) or immune-modulation (IFIT5, IFI16, MMP27, ADAMTS3, MMP3, MMP12). The results of the thesis demonstrate that both mating and components of the sperm-free seminal fluid/plasma elicit gene expression changes in the pre-ovulatory female sperm reservoir of chickens and pigs, some conserved over domestication and fertility-selection.

  • 7.
    Avall Lundqvist, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Nordström, L
    Sjövall, K
    Eneroth, P
    Evaluation of seven different tumour markers for the establishment of tumour marker panels in gynecologic malignancies.1989In: European journal of gynaecological oncology, ISSN 0392-2936, Vol. 10, no 6, 395-405 p.Article in journal (Refereed)
    Abstract [en]

    Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.

  • 8.
    Bailey, Leslie
    Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
    Infection biology of Chlamydia pneumoniae2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    There are two main human pathogens in the family of Chlamydiaceae. Different serovars of Chlamydia trachomatis cause sexually-transmitted disease and eye infections whereas C. pneumoniae (TWAR) is a common cause of community-acquired respiratory infection. Chlamydia species are obligate, intracellular bacteria sharing a unique developmental cycle that occurs within a protected vacuole termed an inclusion. These microorganisms can be distinguished by two different forms: the infectious, metabolically inert elementary body (EB) and the reproducing non-infectious form, termed the reticulate body (RB). The cycle is terminated when re-differentiation of RBs back to infectious EBs occurs. Chlamydia possesses a type III secretion system (T3SS) essential for delivery of effector proteins into the host for host-cell interactions. This virulence system has been systematically characterized in several mammalian pathogens. Due to lack of a tractable genetic system for Chlamydia species, we have employed chemical genetics as a strategy to investigate molecular aspects of the T3SS. We have identified that the T3S-inhibitors INP0010 and INP0400 block the developmental cycle and interfere with secretion of T3S effector proteins in C. pneumoniae and C. trachomatis, without any cytotoxic effect. We have further shown that INP0010 decreases initiation of transcription in C. pneumoniae during the early mid-developmental cycle as demonstrated by a novel calculation, useful for measurement of transcription initiation in any intracellular pathogen. The mechanism regulating the signal(s) for primary as well as terminal differentiation of RBs has not been defined in Chlamydia. We show using T3S-inhibitors that INP0010 targets the T3SS and thereby arrests RB proliferation as well as RB to EB re-differentiation of C. pneumoniae as where INP0400 targets the T3SS and provokes a bacterial dissociation from the inclusion membrane presumed to mimic the natural occurrence of terminal differentiation. The effect of INP0010 on iron-responsive genes indicates a role for T3S in iron acquisition. Accordingly, our results suggest the possibility that C. pneumoniae acquires iron via the intracellular trafficking pathway of endocytosed transferrin. Moreover, we have for the first time presented data showing generalized bone loss from C. pneumoniae infection in mice. The infection was associated with increased levels of the bone resorptive cytokines IL-6 and IL-1beta. In addition, an increased sub-population of T-cells expressed RANKL during infection. Additionally, C. pneumoniae established an infection in a human osteoblast cell line in vitro with a similar cytokine profile as seen in vivo, supporting a causal linkage. Collectively, these data may indicate a previously unknown pathological role of C. pneumoniae in generalized bone loss.

  • 9.
    Berglund, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Separation of Water and Fat Signal in Magnetic Resonance Imaging: Advances in Methods Based on Chemical Shift2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Magnetic resonance imaging (MRI) is one of the most important diagnostic tools of modern healthcare. The signal in medical MRI predominantly originates from water and fat molecules. Separation of the two components into water-only and fat-only images can improve diagnosis, and is the premier non-invasive method for measuring the amount and distribution of fatty tissue.

    Fat-water imaging (FWI) enables fast fat/water separation by model-based estimation from chemical shift encoded data, such as multi-echo acquisitions. Qualitative FWI is sufficient for visual separation of the components, while quantitative FWI also offers reliable estimates of the fat percentage in each pixel. The major problems of current FWI methods are long acquisition times, long reconstruction times, and reconstruction errors that degrade image quality.

    In this thesis, existing FWI methods were reviewed, and novel fully automatic methods were developed and evaluated, with a focus on fast 3D image reconstruction. All MRI data was acquired on standard clinical scanners.

    A triple-echo qualitative FWI method was developed for the specific application of 3D whole-body imaging. The method was compared with two reference methods, and demonstrated superior image quality when evaluated in 39 volunteers.

    The problem of qualitative FWI by dual-echo data with unconstrained echo times was solved, allowing faster and more flexible image acquisition than conventional FWI. Feasibility of the method was demonstrated in three volunteers and the noise performance was evaluated.

    Further, a quantitative multi-echo FWI method was developed. The signal separation was based on discrete whole-image optimization. Fast 3D image reconstruction with few reconstruction errors was demonstrated by abdominal imaging of ten volunteers.

    Lastly, a method was proposed for quantitative mapping of average fatty acid chain length and degree of saturation. The method was validated by imaging different oils, using gas-liquid chromatography (GLC) as the reference. The degree of saturation agreed well with GLC, and feasibility of the method was demonstrated in the thigh of a volunteer.

    The developed methods have applications in clinical settings, and are already being used in several research projects, including studies of obesity, dietary intervention, and the metabolic syndrome.

  • 10.
    Börjesson, Andreas
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Investigations of Strategies to Counteract Proinflammatory Cytokines in Experimental Type 1 Diabetes2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type 1 diabetes (T1D) is a chronic autoimmune disease targeted against the pancreatic β-cells. Proinflammatory cytokines are considered to play a major role in the destruction of the insulin-producing β-cells. This thesis studied strategies to counteract proinflammatory cytokines in experimental T1D. Both animal models for T1D as well as β-cell preparations exposed in vitro to putative noxious conditions were examined.

    In the first study we observed that cytokine treatment of mouse pancreatic islets lacking inducible nitric oxide synthase (iNOS) induced a prolongation of the early stimulatory phase of glucose stimulated insulin secretion. Various experiments led to the conclusion that this prolonged stimulatory effect may involve the DAG/PLD/PKC pathway.

    Next, we transplanted mouse islets deficient in iNOS to spontaneously diabetic NOD mice. We observed a normalization of hyperglycemia but not a delayed allograft rejection compared to transplanted wild type islets. Thus, absence of iNOS in the graft was not sufficient to prolong allograft survival.

    In paper III we found that sustained glucose stimulation of rat pancreatic islets was coupled to a decreased conversion of proinsulin to insulin. Islet treatment with IL-1β was also coupled to a decreased proinsulin conversion. Islet proconvertase activity may be a target in islet damage.

    In paper IV prolactin (PRL) was administered to mice in the multiple low dose streptozotocin model and we observed that PRL enhanced a Th2 response. This may contribute to the protective action by PRL in this model of autoimmune T1D.

    Finally, by examining β-cells overexpressing Suppressor of cytokine signalling 3 (SOCS-3) it was found that this could inhibit IL-1β induced signalling through the NF-κB and MAPK pathways. SOCS-3 overexpression also inhibited apoptosis induced by cytokines in primary β-cells. Lastly, we demonstrated that SOCS-3 transgenic islets were protected in an allogeneic transplantation model.

  • 11.
    Böttiger, Anna
    Örebro University, School of Health and Medical Sciences.
    Genetic variation in the folate receptor-alpha and methylenetetrahydrofolate reductase genes as determinants of plasma homocysteine concentrations2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Elevated total plasma homocysteine (tHcy) is a risk factor for cardiovascular disease and neurocognitive disease such as dementia. The B vitamins folate and B12 are the main de terminants of tHcy. tHcy concentration can also be affected by mutations in genes coding for receptors, enzymes and transporters important in the metabolism of Hcy. This thesis focuses on mutations in the genes for folate receptor-alpha and methylenetetrahydrofolate reductase (MTHFR) and the effect they have on tHcy concentrations.

    Six novel mutations in the gene for folate receptor-alpha were described in Paper I. Taken together they exist in a population with a prevalence of approximately 1% and thus are not unusual. There may be an association of –69dupA and –18C>T to tHcy but for the 25-bp deletion, –856C>T, –921T>C and –1043G>A there is probably no association to tHcy. Mutation screening was continued and four additional mutations, 1314G>A, 1816delC, 1841G>A and 1928C>T, were described in Paper II. The prevalences for the heterozygotes were between 0.5% and 13% in an elderly population. There was no significant difference in prevalence between the elderly subjects and patients with dementia. The 1816(–)-allele and the 1841A-allele were in complete linkage and the haplotype 1816(–)-1841A may possibly have a tHcy raising effect. The 1314G>A and 1928C>T mutations had no association to tHcy.

    The genotype prevalences and haplotype frequencies of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms were determined in a population sample of Swedish children and adolescents (Paper III). The MTHFR 677T-allele was associated with increased tHcy concentrations in both children and adolescents. A small elevating effect of the 1298C-allele and a small lowering effect of the 1793A-allele could be shown. In an epidemiological sample of adults from the Canary Islands, Spain, data for serum folate and vitamin B12 were used for a broader study of the nutrigenetic impact on tHcy (Paper IV). The 677T-allele had a significant tHcy increasing effect in men but not in women. The 1298C-allele had a minor elevating effect on tHcy in men with the 677CT genotype. It was not possible to document any effect of the 1793A-allele on tHcy due to its low prevalence. A slightly superior explanatory power for the genetic impact was obtained using the MTHFR haplotypes in the analysis compared to the MTHFR 677C>T genotype-based approach in both the Swedish children and adolescents and in the Spanish adults. Therefore MTHFR haplotypes should be considered when analysing the impact of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms on tHcy.

    Notwithstanding the large geographical distance between our study populations the haplotype composition is quite similar. The MTHFR 677T-allele is slightly more prevalent in Spain compared to Sweden but it has only an effect on tHcy in the Spanish men. Age, gender and factors linked to the ethnicity of the studied subjects, seem to be able to override the nutrigenetic impact of tHcy-raising genotypes or haplotypes in particular settings, such as in the Spanish women in our study. Gene-nutrient interactions on plasma tHcy levels thus may or may not exist in a certain population. The transferability of nutrigenetic findings may therefore be limited, and must be re-evaluated for each particular setting of age-gender-ethnicity.

  • 12.
    Cristea, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Effects of Ageing and Physical Activity on Regulation of Muscle Contraction2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aims of this study were to investigate the mechanisms underlying (1) the ageing-related motor handicap at the whole muscle, cellular, contractile protein and myonuclear levels; and (2) ageing-related differences in muscle adaptability.

    In vivo muscles function was studied in the knee extensors. Decreases were observed in isokinetic and isometric torque outputs in old age in the sedentary men and women and elite master sprinters. A 20-week long specific sprint and resistance training successfully improved the maximal isometric force and rate of force development in a subgroup of master sprinters.

    In vitro measurements were performed in muscle biopsies from the vastus lateralis muscle. Immunocytochemical and contractile measurements in single membrane permeabilized muscle fibres demonstrated ageing- and gender-related changes at the myofibrillar level. In sedentary subjects, data showed a preferential decrease in the size of muscle fibres expressing type IIa MyHC in men, lower force generating capacity in muscle fibres expressing the type I MyHC isoform in both men and women and lower maximum velocity of unloaded shortening (V0) in fibres expressing types I and IIa MyHC isoforms in both men and women. The master sprinters also experienced the typical ageing-related reduction in the size of fast-twitch fibres, a shift toward a slower MyHC isoform profile and a lower V0 of type I MyHC fibres, which played a role in the decline in explosive force production capacity. The fast-twitch fibre area increased after the resistance training period. A model combining single muscle fibre confocal microscopy with a novel algorithm for 3D imaging of myonuclei in single muscle fibre segments was introduced to study the spatial organisation of myonuclei and the size of individual myonuclear domains (MNDs). Significant changes in the MND size variability and myonuclear organization were observed in old age, irrespective gender and fibre type. Those changes may influence the local quantity of specific proteins per muscle fibre volume by decreased and/or local cooperativity of myonuclei in a gender and muscle fibre specific manner.

    In conclusion, the ageing-related impairments in in vivo muscle function were related to significant changes in morphology, contractile protein expression and regulation at the muscle fibre level. It is suggested that the altered myonuclear organisation observed in old age impacts on muscle fibre protein synthesis and degradation with consequences for the ageing-related changes in skeletal muscle structure and function. However, the improved muscle function in response to a 20-week intense physical training regime in highly motivated physically active old subjects demonstrates that all ageing-related in muscle function are not immutable.

  • 13.
    Dahlström, Örjan
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, The Swedish Institute for Disability Research. Linköping University, Faculty of Arts and Sciences.
    Zetterqvist, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Lundh, Lars-Gunnar
    Department of Psychology, Lund University, Lund, Sweden..
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Functions of Nonsuicidal Self-Injury: Exploratory and Confirmatory Factor Analyses in a Large Community Sample of Adolescents2015In: Psychological Assessment, ISSN 1040-3590, E-ISSN 1939-134X, Vol. 27, no 1, 302-313 p.Article in journal (Refereed)
    Abstract [en]

    Given that nonsuicidal self-injury (NSSI) is prevalent in adolescents, structured assessment is an essential tool to guide treatment interventions. The Functional Assessment of Self-Mutilation (FASM) is a self-report scale that assesses frequency, methods, and functions of NSSI. FASM was administered to 3,097 Swedish adolescents in a community sample. With the aim of examining the underlying factor structure of the functions of FASM in this sample, the adolescents with NSSI who completed all function items (n = 836) were randomly divided into 2 subsamples for cross-validation purposes. An exploratory factor analysis (EFA) was followed by a confirmatory factor analysis (CFA) using the mean and variance adjusted weighted least squares (WLSMV) estimator in the Mplus statistical modeling program. The results of the EFA suggested a 3-factor model (social influence, automatic functions, and nonconformist peer identification), which was supported by a good fit in the CFA. Factors differentiated between social/interpersonal and automatic/intrapersonal functions. Based on learning theory and the specific concepts of negative and positive reinforcement, the nonconformist peer identification factor was then split into 2 factors (peer identification and avoiding demands). The resulting 4-factor model showed an excellent fit. Dividing social functions into separate factors (social influence, peer identification, and avoiding demands) can be helpful in clinical practice, where the assessment of NSSI functions is an important tool with direct implications for treatment.

  • 14. Ekstrand, Carl
    et al.
    Sterning, Marie
    Bohman, Love
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Edner, Anna
    Lumbo-sacral epidural anaesthesia as a complement to dissociative anaesthesia during scrotal herniorrhaphy of livestock pigs in the field2015In: Acta Veterinaria Scandinavica, ISSN 0044-605X, Vol. 57, 33Article in journal (Refereed)
    Abstract [en]

    Background: In Sweden, scrotal or inguinal herniorrhaphy of livestock pigs in the field has traditionally been an important part of the surgical skills training of veterinary students. Few substances meet the legal requirements for field anaesthesia of production animals in the European Union but a protocol based on azaperone-detomidine-butorphanol-ketamine does. Unfortunately the anaesthesia is characterised by unpredictable duration and depth and of abrupt awakenings which is not acceptable from an animal welfare perspective and impedes surgical training. Lumbo-sacral epidural analgesia is proven to provide sufficient analgesia to allow abdominal surgery, but there are few reports on the field use of this loco-regional technique. The study aim was to evaluate whether lumbo-sacral anaesthesia can be safely and successfully used in the field by a veterinary student and whether the combination of dissociative and lumbo-sacral epidural anaesthesia improves analgesia and anaesthesia to guarantee animal welfare during herniorrhaphy in livestock pigs, enabling surgical skills training. Results: Pigs in the control-group (placebo) responded significantly stronger to surgery, with five out of 11 requiring additional doses of detomidine and ketamine. There were no significant differences between groups in respiratory rate, heart rate, blood pressure, SpO(2) or blood gases. SpO(2) levels <94 % were recorded in several pigs in both groups. No post-injection complications were reported at follow-up. Conclusions: The results from this study showed that lumbo-sacral epidural anaesthesia with lidocaine could successfully be administered during dissociative anaesthesia of livestock pigs by a veterinary student and without reported post-injection complications. It improved analgesia and anaesthesia during herniorrhaphy of sufficient duration to enable surgical skills training. The risks and consequences of hypoxaemia and hypoventilation should be considered.

  • 15.
    Ekström, Anette
    et al.
    University of Skövde, School of Life Sciences.
    Nissen, Eva
    University of Skövde, School of Life Sciences.
    Process-oriented training in breastfeeding attitudes and continuity of care improve mothers perception of support2007In: Health Education Research Trends / [ed] Peter R. Hong, Nova Science Publishers, Inc., 2007, 211-225 p.Chapter in book (Refereed)
  • 16.
    Elffors, Jenny
    et al.
    Södertörn University College, School of Business Studies.
    Johannessen, Athena
    Södertörn University College, School of Business Studies.
    Marknadsföring på recept: Läkemedelsmarknadsföring ur ett moraliskt perspektiv2008Independent thesis Basic level (degree of Bachelor), 10 points / 15 hpStudent thesis
    Abstract [en]

    Aims: Overall aims of this thesis are to bring a broader and deeper understanding, from  a moral point of view, of marketing of pharmaceuticals, and to consider whether  there is a reason for separating advertising from information in the sector.

    Methods: A qualitative approach to the subject was used. Methods for data compilation  were semi-structured interviews with representatives for The Swedish Association  of the Pharmaceutical Industry (Läkemedelsindustriföreningen), and studies  of advertisements in The Journal of the Swedish Medical Association (Läkartidningen)  and commercials on a TV channel (TV4). A customised, self-made,  grid was utilised for coding and compiling data from the observations of commercial  material. Following that, the empirical material from interviews as well  as observations has been analysed, using the theory of counter productivity as a  model for ethical audit.

    Results: The authors judge marketing activities of the pharmaceutical industry to be morally  justified. One reason for this judgement is, that the pharmaceutical industry  contributes to an increased well-being among citizens by providing research, research  activities being financed by revenues, which – in turn – are enhanced by  marketing. Another reason is that companies show responsible in the dissemination  of information and that the results of the study indicate sincerity in marketing.  When responsibility is linked to trustworthiness and when availability of information  provided by marketing activities is taken into consideration, there is  also evidence of a morally justifiable behaviour. Advertisements for drugs on  prescription showed more informatively designed than those for over-the-counter  drugs. A more informative and appropriate marketing of non-prescription pharmaceuticals  would enhance the moral reputation of the companies.

  • 17.
    Eliasson, Henrik
    Örebro University, School of Health and Medical Sciences.
    Tularemia: epidemiological, clinical and diagnostic aspects2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Tularemia is a zoonosis caused by the small, fastidious, gram-negative rod Francisella tularensis that appears over almost the entire Northern Hemisphere. In Sweden, tularemia has appeared mainly in restricted areas in northern parts of central Sweden.

    The disease can be transmitted through several routes: direct contact with infected animals, by vectors, through contaminated food or water or through inhalation of aerosolized bacteria. Distinct clinical forms of the disease are seen, depending on the route of transmission. During the last years, tularemia has emerged in new areas in central Sweden, south of the endemic area. The emergence of tularemia in the County of Örebro prompted the investigations presented in this thesis.

    We performed a case-control study, using a mailed questionnaire, to identify risk factors for acquiring tularemia in Sweden (Paper I). After multivariate analysis, mosquito bites and cat ownership could be associated with tularemia in all studied areas while farming appeared as a risk factor only in endemic areas.

    In Paper II, we evaluated a PCR analysis, targeting the tul4 gene, used on samples from primary lesions in patients with ulceroglandular tularemia. The method performed well, with a sensitivity of 78% and a specifi city of 96%. The clinical characteristics of tularemia in an emergent area in Sweden were studied Paper III), using case fi les and a questionnaire. Of 278 cases of tularemia reported during the years 2000 to 2004, 234 had been in contact with a doctor from the Department of Infectious Diseases at Örebro University Hospital, and were thus included. The ulceroglandular form of the disease was seen in 89% of the cases, with the primary lesion, in most cases, on the lower leg. An overwhelming majority of cases occurred during late summer and early autumn, further supporting transmission by mosquitoes. Erythemas overlying the affected lymph node areas were seen in 19% of patients with forms of tularemia affecting peripheral lymph nodes. Late skin manifestations, of various appearances, were seen in 30% of the cases, predominantly in women. A raised awareness of tularemia among physicians in the county during the course of the outbreak was found, as documented by the development of shorter doctor’s delay and less prescription of antibiotics inappropriate in tularemia.

    Finally, we developed a simplifi ed whole-blood lymphocyte stimulation test, as a diagnostic tool in tularemia (Paper IV). The level of IFN-γ, as a proxy for lymphocyte proliferation, was measured after 24-h stimulation. Additionally, a tularemia ELISA with ultra-purifi ed LPS as the antigen was evaluated, showing a high sensitivity. The lymphocyte stimulation test, when performed on consecutive samples from subjects with ongoing tularemia was able to detect the disease earlier in the course of the disease than both the new ELISA and the tube agglutination test. Furthermore, all tularemia cases became positive in the lymphocyte stimulation test within 12 days of disease. In conclusion, this thesis describes risk factors for acquiring tularemia as well as the clinical characteristics of the disease in Sweden. Additionally, a Francisella PCR analysis and a tularemia ELISA based on highly purifi ed LPS is evaluated, and a simplified lymphocyte stimulation test, for early confirmation of the disease, is developed.

  • 18.
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Aspects on stroke outcome: survival, functional status, depression and sex differences in Riks-Stroke, the National Quality Register for Stroke Care2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Stroke is a major cause of death and disability worldwide. In Sweden, about 30 000 strokes occur each year. The aim of this thesis was to analyse survival, functional outcome and self-reported depression after stroke, and to explore possible differences between men and women in stroke care and outcome.

    These studies were based on Riks-Stroke, the Swedish national quality register for stroke care. Information on background variables and treatment were collected during the hospital stay. The patient’s situation and outcome after stroke were followed-up after 3 months. Long term survival was retrieved from the Swedish Population Register (Folkbokföringen).

    Possible sex-differences in stroke care and outcome 3 months after stroke were explored in 24 633 strokes, registered during 2006. In conscious patients, the proportions treated at stroke units were similar for men and women. Men and women had equal chance to receive thrombolytic therapy or secondary prevention with oral anticoagulants. Compared to men, women were less likely to develop pneumonia, but more likely to experience deep venous thromboses and fractures during hospital stay. Women had worse 3-month survival and functional outcome, differences that were explained by their higher age and impaired level of consciousness on admission. Women felt more depressed and perceived their health as worse than men did. Women were also less satisfied with the care they had received in the hospital.

    The agreement between self-reported functional outcome 3 months after stroke and the commonly used modified Rankin Scale (mRS) was explored in 555 stroke survivors from 4 hospitals during May-September 2005. Riks-Stroke’s self-reported questions classified 76% of the patients into correct mRS grade.

    The association between functional outcome 3 months after stroke and 3-year survival was assessed in 15 959 men and women who had had a stroke during 2001-2002. Patients with estimated mRS grades 3, 4 and 5 had hazard ratios for death of 1.7, 2.5 and 3.8, respectively, as compared with patients with lower grades, 0-2. Depressed mood, male sex, high age, diabetes, smoking, antihypertensive therapy at onset and atrial fibrillation were also identified as predictors of poor survival.

    Self-reported depression 3 months after stroke and use of antidepressants were analysed in 15 747 stroke survivors from 2002. Fourteen percent felt depressed 3 months after stroke. Female sex, age <65, previous stroke, living alone or in institution, or being dependent in activities of daily living (ADL) were factors associated with self-reported depression. At the follow-up, 22% of the men and 28% of the women were using antidepressant medication, which were approximately twice as many as in the general population. Still, 8% of all patients in Riks-Stroke reported depressive mood but no treatment with antidepressants.

    In conclusion, men and women with stroke in Sweden experience similar treatment and outcome in most aspects. Patient-reported functional outcome can be reliably transformed to a standard disability scale. Impaired functional outcome three months after stroke is an independent predictor of poor long-term survival. Depressive mood is common after stroke and is associated with poor survival and impaired functional outcome.

  • 19.
    Erlandsson, Kerstin
    et al.
    Mälardalen University, School of Health, Care and Social Welfare.
    Lindgren, Helena
    Högskolan Dalarna.
    Being a Resource for Both Mother and Child2011In: The Journal of Perinatal Education, ISSN 1058-1243, Vol. 20, no 2, 91-99 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to describe fathers' experiences of being present on a postnatal ward and during the first days at home following a complicated birth. Fifteen fathers were interviewed, and content analysis was used for the analysis. The theme illustrated that fathers were a resource for both mother and child through practical and emotional engagement. The categories describe how the father empowers the mother and illustrates adapting to new family roles. Following complicated birth, fathers should be invited to stay around-the-clock on postnatal wards because it gives them the opportunity to place their resources at the disposal of mother and child. In antenatal courses, fathers should be prepared for their empowering role after a complicated birth

  • 20.
    Fuchs, Dieter
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Novel Treatment Modalities for High-Risk Neuroblastoma: Studies in Animal Models2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Neuroblastoma, the most common extracranial solid tumor of childhood, is a heterogeneous tumor. In some patients, the tumor can go into spontaneous regression and disappear whereas other patients have rapidly growing tumors with a poor prognosis. The overall long-term survival rate in patients with high-risk neuroblastoma is less than 30%, indicating the need for new treatment strategies.

    Angiogenesis inhibition hampers the formation of new blood vessels, thereby limiting the tumors’ metabolic exchange. Neuroblastoma is rapidly growing and high tumor angiogenesis has been associated with poor outcome. Therefore, the aim of this thesis was to investigate the effect of novel treatment modalities for angiogenesis inhibition on high-risk neuroblastoma xenografts. For that purpose, we used subcutaneous mouse models and characterized orthotopic mouse models for high-risk neuroblastoma.

    We found that xenotransplantation of neuroblastoma cells into the adrenal gland of SCID and SCID beige mice resulted in orthotopic tumors resembling clinical neuroblastoma in respect to tumor site, growth and spread. Using contrast-enhanced ultrasound, we observed that the receptor tyrosine kinase inhibitor SU11248 reduced orthotopic neuroblastoma growth and spread by reducing tumor angiogenesis.

    In subcutaneous xenografts for high-risk neuroblastoma, valuable for studies requiring continuous assessment of tumor volume, we demonstrated that immune-neutralizing VEGF with the anti-VEGF antibody bevacizumab significantly reduced neuroblastoma growth.

    Finally, we found that formulations of the chemotherapeutic drug GMX1778 inhibited angiogenesis and induced tumor regression in a dose dependent manner without host toxicity. We showed that relapsing tumors remained responsive to GMX-therapy without accelerated growth or induced drug resistance.

    In conclusion, SU11248, bevacizumab, and formulations of the active compound GMX1778 may become useful for treating high-risk neuroblastoma.

  • 21.
    Gisslén, Karl
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    The patellar tendon in junior elite volleyball players and an Olympic elite weightlifter2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The principal aim of the present thesis was to prospectively follow (clinical status and ultrasound + Doppler findings) the patellar tendons in the young elite volleyball players at the Swedish National Centre for high school volleyball in Falköping. In an Olympic weightlifter with chronic painful jumper´s knee, the effects of treatment with sclerosing injections followed by early instituted very heavy weightlifting training, was also evaluated.

    First, in a prevalence study, we demonstrated that the clinical diagnosis patellar tendinopathy-jumper’s knee, together with structural tendon changes and vascularisation in the painful area of the tendon, was demonstrated in 12/114 tendons in Swedish junior elite volleyball players, but not in any tendons of individually matched (age, height and weight) not regularly sports active controls. Structural tendon changes alone was demonstrated among the volleyball players but also among the controls.

    In a 7 months prospective study of a total of 120 tendons, we demonstrated that the clinical diagnosis patellar tendinopathy-jumper’s knee was associated with neovessels/vascularity in the area with structural tendon changes in 17/19 tendons. Seventy tendons that at start were clinically normal, and had normal ultrasound + Doppler findings, remained clinically normal after 7 months with intensive training and playing volleyball.

    In a 3-year prospective study it was demonstrated that normal clinical tests and normal ultrasound + Doppler findings at school start, indicated a low risk (8%) for these players to sustain patellar tendinopathy-jumper’s knee during the 3 school years with intensive training and playing.

    In a case study, involving an Olympic elite weightlifter with chronic painful patellar tendinopathy-jumper’s knee, successful treatment with ultrasound and Doppler-guided injection of the sclerosing agent polidocanol, allowed for pain-free very heavy weight training two weeks after treatment. Further heavy weightlifting training on a daily basis, preparing for European Championships, was done without causing tendon rupture and/or pain.

    Key words: Jumper’s knee, Patellar tendinopathy, Chronic pain, Ultrasonography, Doppler, Neovascularisation, Volleyball, Weightlifting

  • 22.
    Guez, Michel
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    Chronic neck pain: An epidemiological, psychological and SPECT study with emphasis on whiplash-associated disorders2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Chronic neck pain, a common cause of disability, seems to be the result of several interacting mechanisms. In addition to degenerative and inflammatory changes and trauma, psychological and psychosocial factors are also involved. One common type of trauma associated with chronic neck pain is whiplash injury; this sometimes results in whiplash-associated disorder (WAD), a controversial condition with largely unknown pathogenetic mechanisms. We studied the prevalence of chronic neck pain of traumatic and non-traumatic origin and compared the prevalence of, sociodemographic data, self-perceived health, workload and chronic lowback pain in these groups. In a ready-made questionnaire (MONICA study), we added questions about cervical spine and low-back complaints. 6,000 (72%) completed a self-administered questionnaire. 43% reported neck pain: 48% of women and 38% of men. Women of working age had more neck pain than retired women, a phenomenon not seen in men. 19% of the studied population suffered from chronic neck pain and it was more frequent in women. A history of neck trauma was common in those with chronic neck pain. Those with a history of neck trauma perceived their health worse and were more often on sick-leave. About 50% of those with traumatic and non-traumatic chronic neck pain also had chronic low-back pain.

    We assessed the subjective and objective neuropsychological functioning in 42 patients with chronic neck pain, 21 with a whiplash trauma, and 21 without previous neck trauma. Despite cognitive complaints, the WAD patients had normal neuropsychological functioning, but the WAD group especially had deviant MMPI results—indicating impaired coping ability and somatization.WAD patients had no alterations in cerebral blood-flow pattern, as measured by rCBF-SPECT and SPM analysis, compared to healthy controls. This contrasts with the non-traumatic group with chronic neck pain, which showed marked blood-flow changes. The blood-flow changes in the non-traumatic group were similar to those described earlier in pain patients but— remarkably enough—were different from those in the WAD group. Chronic neck pain of whiplash and non-traumatic origin appears to be unique in some respects. A better understanding of the underlying pathological mechanisms is a prerequisite for prevention of the development of such chronic pain syndromes and for improvement of the treatment of patients with severe symptoms.

  • 23.
    Gustafsson, Mattias
    Örebro University, Department of Clinical Medicine.
    Vilken betydelse har skelettscintigrafi vid diagnos av scaphoideumfraktur?2007Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    En scaphoideumfraktur är den vanligaste frakturen bland karpalbenen i handen. Frakturen orsakas vanligen av ett kraftigt extensionsvåld mot handleden.

    Scaphoideums stora rörlighet i handen och dess begränsade blodförsörjning bidrar till att scaphoideumfrakturer kan vara svårläkta.

    Scaphoideumfrakturer kan vara svåra att påvisa på konventionell röntgen, även vid upprepade undersökningar. Visar konventionell röntgen ett negativt resultat, men klinisk misstanke om fraktur kvarstår, finns olika undersökningsmetoder att tillgå för att en säker diagnos ska kunna ställas.

    Syftet med den här litteraturstudien var att undersöka betydelsen av skelettscintigrafi som undersökningsmetod vid diagnos av scaphoideumfraktur.

    Resultatet visar att skelettscintigrafi har stor betydelse vid diagnos av en scaphoideumfraktur.

    Kan inte en säker diagnos ställas på konventionell röntgen är skelettscintigrafi en metod som båda kan påvisa och exkludera en scaphoideumfraktur.

  • 24.
    Haftor, Darek
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Computer Science, Physics and Mathematics.
    Mirijamdotter, AnitaLinnaeus University, Faculty of Science and Engineering, School of Computer Science, Physics and Mathematics.
    Information and Communication Technologies, Society and Human Beings: Theory and Framework (Festschrift in honor of Gunilla Bradley)2011Collection (editor) (Other academic)
    Abstract [en]

    Information and Communication Technologies, Society and Human Beings: Theory and Framework addresses the extensive area of effects of ICT on human beings and the interaction between ICT, individuals, organizations, and society. This premier reference source features contributions from over 45 distinguished researchers from around the world, each presenting high quality research on social informatics, human computer interaction, organizational behavior, and macro-ergonomics. This unique publication is perfect for students, teachers, researchers, engineers, practitioners, managers, policy-makers, and media alike.

  • 25.
    Hahn-Strömberg, Victoria
    Örebro University, School of Health and Medical Sciences.
    Cell adhesion proteins in different invasive patterns of colon carcinomas: a morphometric and molecular genetic study2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Colorectal carcinoma is the second most common type of cancer in both men and women in Sweden. Cancer of the colon and rectum are often considered together and their ten year survival rate is approximately 50 – 60 % depending on sex and location. Different histopathological characteristics of such cancers, including the complexity of growth, are of importance for prognosis.

    This thesis has compared different morphometric methods in order to achieve a quantitative and objective measurement of the invasive front of colon carcinoma. Since the growth pattern is dependent on the cell adhesiveness of different proteins we studied the distribution and localization of E-cadherin, Beta-catenin, Claudin 1,2,7 and Occludin as well as screened the genes for mutations.

    We found a perturbed protein expression of E-cadherin, Beta-catenin, Claudin 1,2,7 and Occludin in tumor sections compared to normal mucosa, but no relation to tumor volume or growth pattern could be seen. The tumor volume was found to be correlated to the growth pattern but not responsible to the perturbed protein expression. In the mutation screening we found a SNP in exon 13 the E-cadherin gene in the tumor, as well as in exon 2 of Claudin 1 and exon 4 of Claudin 7 in both tumor and normal mucosa. No correlation between mutations and growth pattern or tumor volume was found.

    In conclusion, this thesis shows that the computer image analysis with estimation of fractal dimension and number of free tumor cell clusters is superior to the semi quantitative visual grading of tumor invasive complexity. The aberrant expression of cell adhesion proteins in the tumor compared to normal mucosa as well as polymorphisms in the cell adhesion genes CLDN1 and CLDN7 in both tumor and normal mucosa can suggest that these aberrations are important in the tumorigenesis of colon carcinoma.

     

  • 26.
    Heiene, Reidun
    et al.
    University of Utrecht.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Neusüß, Christian
    Aalen University.
    Hedeland, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Carbamylated hemoglobin project AKI vs CKD- or the magnitude of the chronic component2016Conference paper (Refereed)
  • 27.
    Henriksson, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Development of body composition and its relationship with physical activity in healthy Swedish children: A longitudinal study until 4.5 years of age including evaluation of methods to assess physical activity and energy intake2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Childhood obesity according to the World Health Organization is one of the most serious public health challenges of the 21st century. The proportion of childhood obesity is high both globally and in Sweden. This is of great concern since obese children tend to stay obese in adulthood. In order to develop strategies to prevent early childhood obesity more knowledge is needed regarding factors explaining why children become overweight and obese. Preventive strategies require accurate and easy-to-use methods to assess physical activity in response to energy expenditure as well as energy intake in young children, but such methods are largely lacking or have shown limited accuracy. The aims of this thesis were: 1) to describe the longitudinal development of body composition from 1 week to 4.5 years of age; 2) to study relationships between measures of body composition and the physical activity level (PAL) at 1.5 and 3 years of age; 3) to evaluate if heart rate recording and movement registration using Actiheart can capture variations in total energy expenditure (TEE) and activity energy expenditure (AEE) at 1.5 and 3 years; 4) to evaluate the potential of a 7-day activity diary to assess PAL at 1.5 and 3 years of age; 5) to evaluate a new tool (TECH) using mobile phones for assessing energy intake at 3 years of age.

    Healthy children were investigated at 1 and 12 weeks (n=44), at 1.5 (n=44), 3 (n=33) and 4.5 (n=26) years of age. Body composition was measured using air-displacement plethysmography at 1 and 12 weeks and at 4.5 years of age. At 1.5 and 3 years, body composition, TEE, PAL and AEE were assessed using the doubly labelled water method and indirect calorimetry. Heart rate and movements were recorded using Actiheart (four days) and physical activities were registered using the 7-day diary. Energy intake was assessed using TECH during one complete 24-hour period.

    Average percentage of total body fat (TBF) and average fat mass index (FMI) were higher (+3 to +81 %), while fat-free mass index (FFMI) was slightly lower (-2 to -9 %), in children in the study from 12 weeks until 4.5 years of age when compared to corresponding reference values. A relationship between TBF% and PAL was found both at 1.5 and 3 years of age. At 3 years, but not at 1.5 years, this could be explained by a relationship between PAL and FFMI. Actiheart recordings explained a significant but small fraction (8%) of the variation in free-living TEE at 1.5 and 3 years, and in AEE (6 %) at 3 years, above that explained by body composition variables. At 1.5 and 3 years of age, PAL estimated by means of the activity diary using metabolic equivalent (MET) values by Ainsworth et al. was not significantly different from reference PAL, but the accuracy for individuals was low. Average energy intake assessed by TECH was not significantly different from TEE. However, the accuracy for individuals was poor.

    The results of this thesis suggest that 1) The higher body fatness of the children in the study compared to the corresponding reference values may indicate the presence of a secular trend in body composition development characterized by a high body fatness. 2) Body fatness might counteract physical activity at 1.5 years of age when the capacity to perform physical activity is limited, but not at 3 years of age when such a capacity has been developed. 3) Actiheart recordings explained a significant but small fraction of the variation in TEE at 1.5 and 3 years, and in AEE at 3 years of age, above that explained by body composition variables. 4) The activity diary and TECH produced mean values in agreement with reference PAL and TEE, respectively, but the accuracy for individual children was low.

    In conclusion, the results of this thesis suggest the presence of a secular trend in body composition development in healthy Swedish children, from infancy up to 4.5 years of age, which is characterized by a high body fatness. Methods to assess physical activity and energy intake at 1.5 and 3 years of age provided some promising results on a group level, although further research is needed to increase the accuracy of these methods in individual children.

  • 28.
    Henriksson, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bonn, E. Stephanie
    Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
    Bergström, Anna
    Karolinska Institutet, Institute of Enviromental Medicine, Stockholm, Sweden.
    Bälter, Katarina
    Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden.
    Bälter, Olle
    Royal Institute of Technology, School of Computer Science and Communication, Stockholm, Sweden.
    Delisle, Christine
    Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden.
    A New Mobile Phone-Based Tool for Assessing Energy and Certain Food Intakes in Young Children: A Validation Study2015In: JMIR mhealth and uhealth, E-ISSN 2291-5222, Vol. 3, no 2, e38Article in journal (Refereed)
    Abstract [en]

    Background: Childhood obesity is an increasing health problem globally. Obesity may be established already at pre-school age. Further research in this area requires accurate and easy-to-use methods for assessing the intake of energy and foods. Traditional methods have limited accuracy, and place large demands on the study participants and researchers. Mobile phones offer possibilities for methodological advancements in this area since they are readily available, enable instant digitalization of collected data, and also contain a camera to photograph pre- and post-meal food items. We have recently developed a new tool for assessing energy and food intake in children using mobile phones called the Tool for Energy Balance in Children (TECH). Objective: The main aims of our study are to (1) compare energy intake by means of TECH with total energy expenditure (TEE) measured using a criterion method, the doubly labeled water (DLW) method, and (2) to compare intakes of fruits and berries, vegetables, juice, and sweetened beverages assessed by means of TECH with intakes obtained using a Web-based food frequency questionnaire (KidMeal-Q) in 3 year olds. Methods: In this study, 30 Swedish 3 year olds were included. Energy intake using TECH was compared to TEE measured using the DLW method. Intakes of vegetables, fruits and berries, juice, as well as sweetened beverages were assessed using TECH and compared to the corresponding intakes assessed using KidMeal-Q. Wilcoxon matched pairs test, Spearman rank order correlations, and the Bland-Altman procedure were applied. Results: The mean energy intake, assessed by TECH, was 5400 kJ/24h (SD 1500). This value was not significantly different (P=.23) from TEE (5070 kJ/24h, SD 600). However, the limits of agreement (2 standard deviations) in the Bland-Altman plot for energy intake estimated using TECH compared to TEE were wide (2990 kJ/24h), and TECH overestimated high and underestimated low energy intakes. The Bland-Altman plots for foods showed similar patterns. The mean intakes of vegetables, fruits and berries, juice, and sweetened beverages estimated using TECH were not significantly different from the corresponding intakes estimated using KidMeal-Q. Moderate but statistically significant correlations (ρ=.42-.46, P=.01-.02) between TECH and KidMeal-Q were observed for intakes of vegetables, fruits and berries, and juice, but not for sweetened beverages. Conclusion: We found that one day of recordings using TECH was not able to accurately estimate intakes of energy or certain foods in 3 year old children.

  • 29.
    Henriksson, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Britt
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Flinke Carlsson, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Development of body composition and its relationship with physical activity: A longitudinal study of Swedish children until 4·5 years of age2015Manuscript (preprint) (Other academic)
    Abstract [en]

    In order to develop strategies to prevent early childhood obesity more knowledge about longitudinal body composition development is needed. Previous studies have shown that there is a negative relationship between the physical activity level (PAL) and total body fat (TBF) in children. The aims of this study were: 1) To describe the longitudinal development of body composition from 1 week to 4·5 years of age. 2) To study the relationships between measures of body composition and PAL at 3 years of age. 3) To compare the relationships between body composition measures and PAL at 3 years of age to the corresponding relationships at 1·5 years of age. Body composition was measured using air-displacement plethysmography at 1 week, 12 weeks and at 4·5 years of age. At 1·5 and 3 years body composition and PAL were assessed using the doubly labelled water method and indirect calorimetry. The results showed that TBF% and fat mass index (FMI) were higher than corresponding reference values, during infancy and childhood. We found a relationship between TBF% and PAL at 3 years of age but this was explained by a relationship between PAL and fat-free mass index (FFMI). The corresponding relationship at 1·5 years of age could not be explained by a relationship between PAL and FFMI. In conclusion, the children in this study had higher body fatness compared to the corresponding reference values. This may indicate an identification of a secular trend in body composition development which is characterized by a high body fatness. Our findings also suggest that body fatness might counteract physical activity at 1·5 years of age when the capacity to perform physical activity is limited, however this result was not observed at 3 years of age when such a capacity has been developed.

  • 30.
    Henriksson, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Department of Biosciences and Nutrition, Karolinska Institute, NOVUM, Huddinge, Sweden.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Glucose, insulin, and the insulin-like growth factor binding protein 1 in the circulation of pregnant women in relation to their own body composition and to that of their infants2015Manuscript (preprint) (Other academic)
    Abstract [en]

    Aim: Intrauterine factors influence infant size and body composition but the mechanisms involved are incompletely known. We studied relationships between the body composition of pregnant women and variables related to their glucose homeostasis, i.e. glucose, insulin, HOMA-IR (homeostasis model assessment-insulin resistance), haemoglobin A1c and IGFBP-1 (insulin-like growth factor binding protein 1), in their circulation and related these variables to the body composition of their infants.

    Methods: Body composition of 209 women in gestational week 32 and of their healthy, singleton and full-term one-week-old infants was measured using air displacement plethysmography. Glucose homeostasis variables were assessed in gestational week 32.

    Results: Insulin/HOMA-IR were positively related to body mass index, fat mass index and fat mass (r2=0.32-0.36, P<0.001) of the women. Their glucose, insulin and HOMA-IR values were positively (P≤0.009) associated, while IGFBP-1was negatively (P=0.001) associated, with infant fat mass. Insulin and HOMA-IR were positively associated with fat mass of daughters (P<0.001), but not of sons (P≥0.65) (Sex-interaction: P≤ 0.042).

    Conclusion: Glucose homeostasis variables of pregnant women are related to their own body composition and to that of their infants. The results suggested that a previously identified relationship between fat mass of mothers and daughters is mediated by insulin resistance.

  • 31.
    Henriksson, Pontus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Löf, Marie
    Department of Biosciences and Nutrition, Karolinska Institute, NOVUM, Huddinge, Sweden.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Parental fat-free mass is related to the fat-free mass of infants and maternal fat mass is related to the fat mass of infant girls2015In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, no 5, 491-497 p.Article in journal (Refereed)
    Abstract [en]

    Aim: Existing studies suggest that weight and body composition of parents influence the size and body composition of their offspring, but are often inconclusive and conducted by means of inappropriate body composition methodology. Our aim was to study infant size and body composition variables in relation to body composition variables of their mothers and fathers in a well-nourished population using an accurate methodology.

    Methods: Between 2008 and 2011, we used air displacement plethysmography to measure the body composition of 209 parent–infant units. Parents were measured when women were in gestational week 32. Their healthy, singleton, full-term infants were measured at 1 week.

    Results: Infant fat-free mass in grams was positively related (p ≤ 0.007) to the fat-free mass in kilograms of the mothers (15.6 g/kg) and the fathers (9.1 g/kg). Furthermore, the fat mass of the daughters, but not of the sons, was positively related to the fat mass of the mothers (5.8 g/kg, p = 0.007).

    Conclusion: This study found associations between the fat-free mass of parents and infants and an association between the fat mass of mothers and their infant girls. These findings may help to understand early life factors behind overweight and obesity.

  • 32.
    Hjelmblink, Finn
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Understanding Life After Stroke2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Stroke is an acute, neurological dysfunction of vascular origin with sudden occurrence and it influences physical, cognitive and psychological functions. Initial treatment aims at eliminating or reducing the brain damage. Soon, however, the influence of the stroke on the entire life of stroke survivors has to be considered.

    This thesis explores the meaning of life after stroke to 19 elderly stroke survivors during the first year post stroke. Survivors were interviewed twice and the interviews were analysed through qualitative methods.

    Study I was about four survivors who delayed hospital arrival far beyond time limits for trombolytic treatment. The survivors had a strong need for control of body, autonomy and integrity and they demanded to be encountered in consultations as a person by a person. To make them search for emergency evaluation in time might demand an emergency care treating them according to these needs.

    In Study II the voice of an aphasic survivor was heard. Because of the damaged language his rehabilitation unilaterally focussed on language training and his need for comprehensive support and planning for the future was not observed. Implementation of a qualitative research method for text analysis adapted to practical use in dialogues with aphasic persons might ensure these survivors an adequate rehabilitation.

    Study III showed how time models in narratives helped stroke survivors to overcome uncertainty and recreate narrative coherence in their lives. Professionals can support survivors through revealing and reinforcing the meaning of these models.

    Study IV found that the meaning of rehabilitation to stroke survivors was social reintegration. Many probably did not socially reintegrate because their own strategies and subjectively experienced disabilities were unacknowledged in their rehabilitation. Through integrating illness-as-lived perspectives with biomedical perspectives, subjective dysfunctions and rehabilitation strategies of survivors could be acknowledged in stroke rehabilitation.

  • 33.
    Holdstock, Camilla
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Gastric Bypass in Morbid Obesity: Postoperative Changes in Metabolic, Inflammatory and Gut Regulatory Peptides2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis examines the effect of surgical weight loss on gut and adipose tissue peptides involved in appetite regulation and energy homeostasis in morbidly obese humans. Roux-en-Y gastric bypass (RYGBP) is the gold standard operation used for effective long-term weight loss and improved health. The exact mechanisms for this outcome are under investigation.

    We measured ghrelin, a recently discovered hunger hormone, insulin, adiponectin and leptin along with anthropometry measures in 66 morbidly obese patients prior to and 6 and 12 months after RYGBP. Impressive weight loss occurred postoperatively as did alterations in the peptides. Consistent correlations were found between weight, leptin, ghrelin and insulin. The main findings were low ghrelin concentrations in obesity and an increase after RYGBP.

    We explored inflammatory proteins C-reactive protein (CRP), serum amyloid A and interleukin-6 before and during massive weight loss 6 and 12 months after RYGBP in morbidly obese subjects. The studied proteins declined after surgery and a correlation between CRP and homeostatic model of assessment for insulin resistance, independent of BMI, strongly linked insulin resistance and inflammation. CRP declined most in insulin-sensitive subjects.

    We examined the excluded stomach mucosa and vagus nerve by measuring gastrin, pepsinogen I (PGI), pancreatic polypeptide (PP) and ghrelin levels during week 1 and year after RYGBP. Ghrelin levels rose with weight loss but declined 24-hours after surgery, like PP, indicating transient vagal nerve damage. Low levels of gastrin and PGI suggest a resting mucosa.

    We evaluated gut peptides: peptide YY (PYY), glucaogon like peptide-1 (GLP-1), pro-neurotensin (pro-NT) and PP, in lean (young and middle-aged), obese and postoperative RYGBP subjects pre- and postprandially. RYGBP subjects had exaggerated levels of PYY and GLP-1 postprandially and higher basal proNT levels, implying a ‘satiety peptide tone’ that may contribute to the maintenance of weight loss.

    In summary, RYGBP results in marked weight loss and alterations in gut and adipose tissue peptides involved in appetite regulation and energy homeostasis. These postoperative peptide changes may contribute to impressive weight loss observed after RYGBP.

  • 34.
    Idberg, Anna
    et al.
    Linnaeus University, Faculty of Health, Social Work and Behavioural Sciences, School of Health and Caring Sciences.
    Ulbaek, Lena
    Linnaeus University, Faculty of Health, Social Work and Behavioural Sciences, School of Health and Caring Sciences.
    Äldre kvinnors sexuella välbefinnande2010Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Sexuality among older persons are just as important to quality of life as it is to younger people. The sexual ability and sexual needs will continue up in years. An active sex life is good for the sexual satisfaction.

    Objective: The objective was to examine factors that have a positive impact on older women's sexual satisfaction.

    Method: A quantitative method was used on already collected material, consisting of extensive surveys collected during the years of 2000-2003. The main variable sexual satisfaction has been tested against several relevant variables. The analytical methods used were chi-square test, univariate analysis and finally a multivariate analysis. We chose to examine the positive odds ratio, (POR), that affects the sexual satisfaction positively. Results: Among the respondents 25% estimated that they had very good sexual satisfaction. The results indicates to be appreciated at home and happy with ones own body affected the sexual satisfaction positively. Having a good mood and not have passed menopause also have a positive affect of the older womens sexual satisfaction.

  • 35.
    Ivarsson, Niklas
    Örebro University, School of Health and Medical Sciences.
    An inquiry to a possible fatty acid metabolism defect due to carnitine deficiency in patient fibroblast, analysed with a tritium release assay2008Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The formation of tritiated water from [9,10-3H]-palmitic acid has been recommended as an adequate screening method to detect patients with fatty acid oxidation disorders. Intact cultured fibroblasts from three patients (a young girl, the Mother and Grandfather) plus controls have been studied using this method with 3H-palmitic acid at the presence or absent of excess of carnitine. The patients were suspected to have an aberrant carnitine transport over the cell membrane, which probably could secondary affects the fatty acid metabolism.

    No differences were found in β-oxidation of 3H-palmytic acid between fibroblasts from patients compared to healthy controls. Excess of carnitine did not shown any effect on β-oxidation of 3H-palmytic acid either

    The results showed that the patients’ fibroblasts did not have a decreased β-oxidation capacity and no significant difference when treated with carnitine compared to the matched healthy controls. This study cannot link the patient’s symptoms with an aberrant carnitine transport over cell membrane or any defect in β-oxidation of fatty acid metabolism.

  • 36.
    Jemtå, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Children and Adolescents Living with Mobility Impairment2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aim: This thesis aims to describe perceived overall well-being, coping strategies, experiences of intimacy and sexuality, and global and dimension-specific self-esteem among children and adolescents with mobility impairment.

    Methods: The study included 141 children and adolescents aged 7–18 years with mobility impairment. Data was gathered by comprehensive semi-structured interviews and the self-report inventories “Children’s Coping Strategies Checklist” (CCSC) and “I Think I am”. Perceived overall well-being was measured by the nine-grade visual “Snoopy scale”. Motor function and pain were measured by the BL motor assessment, and independence or dependence by Katz Index of Independence in Activities of Daily Living.

    Results: The majority reported a favourable level of perceived overall well-being and positive global and dimension-specific self-esteem. Lower global self-esteem was significantly related to: greater age, being a first-generation immigrant, having an acquired disease or injury and experience of pain, while lower level of perceived overall well-being was significantly related to all of these in addition to not living with both parents. Generally, children and adolescents identified themselves as sexual beings and most expressed future aspirations as living together with partner having children. However, many had limited or no experience of partner-related intimacy and sexual activities, and socio-demographic and disability characteristics had a marginal influence. A history of sexual abuse was reported by 7% in the age cohort 13–18 years. A four-dimensional model of coping strategies including “active coping”, “distraction”, “avoidance” and “support seeking” strategies provided an adequate fit to the CCSC data. Three of the four strategies, all except “avoidance”, were significantly related to several demographic and disability features. Well-being was not significantly related to coping strategies, although the higher the trust in the strategies, the higher the estimation of well-being.

    Conclusion: The understanding of vulnerability factors as well as identification of coping strategies among children and adolescents with mobility impairment is essential for providing proper care, treatment and support during childhood and adolescence.

  • 37.
    Jiang, Wei
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Regeneration in the adult brain after focal cerebral ischemia: exploration of neurogenesis and angiogenesis2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Ischemic stroke ranks as the third major cause of clinical mortality and the leading cause of handicap in adults. Each year, stroke occurs in about 30,000 Swedes. The severity of an acute ischemic stroke depends mainly on the degree and duration of local cerebral blood flow (lCBF) reduction. Prompt reperfusion improves neurological deficits, spontaneous electrical activity, energy metabolism, cerebral protein synthesis (CPS), and tissue repair, among which cell proliferation (neurogenesis, gliosis) and revascularization (angiogenesis) may have important functional and therapeutic implications.

    Aims of the thesis: (1) To establish the photothrombotic ring stroke(PRS) model with late spontaneous reperfusion in adult mice; (2) To explore angiogenesis and neurogenesis in adult brain after focal cerebral ischemia.

    Materials and Methods: The PRS model in C57 BL adult mice and the middle cerebral artery suture occlusion (MCAO) model in adult Wistar rats were used. The 5-bromodeoxyuridine (BrdU) was delivered into animal after stroke induction to label DNA duplication. CBF, CPS and adenosine triphosphate (ATP) were measured by laser-Doppler flowmetry (LDF), [14C]–Iodoantipyrine and [3H]-Leucine double tracer autoradiography, and bioluminescence, respectively. Immunocytochemistry / immunofluoresence were performed to detect different proteins. The cell marker colocalization was analyzed by three-dimension (3-D) confocal. The cell counting was performed with a stereological counting system.

    Results: The PRS model was established in adult mice by irradiating the exposed skull with a 514.5 nm argon laser ring beam (3 mm diameter, 0.21 mm thick) at an intensity of 0.65 W/cm2 for 60s, with concurrent erythrosin B (4.25 mg/kg) intravenous infusion for 15s. The central cortical region within the ring locus was progressively encroached by an annular ring-shaped perfusion deficit, where lCBF LDF declined promptly to 43% of the baseline value at 30 min post irradiation. The lCBF-IAP amounted to 46-17-58 ml/100g/min, where CPS varied from 57-38-112% at 4h-48h-7days post ischemia. ATP declined at 4h, achieved its maximum level at 48h and was markedly reduced at 7 days postischemia. Morphologically, at 4h some neurons in the region at-risk appeared swollen, at 48h the majority were severely swollen, eosinophilic and pyknotic. Tissue morphology became partly restored at 7 days post stroke, when numerous cortical cells were immunolabeled by BrdU or the mitosis-specific marker phosphorylated histone H3 (Phos-H3). Some of these cells were even doubly immunopositive to the neuron-specific marker Neu N and the astrocyte marker GFAP, as analyzed by 3-D confocal. In adult rats exposed to MCAO, widespread BrdU-immunolabeled cells appeared in the cortex, ipsilateral striatum and dentate gyrus of the hippocampus. Some of which were doubleimmunolabeled by the neuron specific markers Map-2, β-tubulin III and Neu N as analyzed by 3-D confocal. As early as 24h postischemia, BrdU-immunopositive endothelial cells were aligned as microvessels, some of which exhibited distinguishable lumens in the ischemic boundary zone, where VEGF-A, B, C proteins and their receptors flt-1, fik-1, flt-4 were overexpressed at 72h after MCAO.

    Conclusion: PRS model in adult mice elicits a dynamic deterioration and then restoration of local CBF, CPS, ATP and tissue morphology in the spontaneously reperfused cerebral cortex at 7d after stroke, where cortical neurogenesis and gliosis occurred. In adult rats with MCAO, neurogenesis occurred at 30 and 60d in the penumbral cortex and striatum. Angiogenesis occurred as early as 24h, which contributed to the spontaneous reperfusion frequently observed in this setting of acute ischemic stroke.

  • 38. Jitpean, Supranee
    et al.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Pettersson, Ann
    Höglund, Odd V
    Ström, Bodil Holst
    Hagman, Ragnvi
    Decreased plasma Chromogranin A361-372 (Catestatin) but not Chromogranin A17-38 (Vasostatin) in female dogs with bacterial uterine infection (pyometra).2015In: BMC veterinary research, ISSN 1746-6148, Vol. 11, no 1, 14- p.Article in journal (Refereed)
    Abstract [en]

    BackgroundPyometra often induces systemic inflammatory response syndrome (SIRS) and early diagnosis is crucial for survival. Chromogranin A (CgA) is a neuroendocrine secretory protein that is co-released with catecholamines from the adrenal medulla and sympathetic nerve endings. A prognostic value of CgA has been found in humans that are critically ill or that have SIRS associated with infection. CgA has not yet been studied in dogs with bacterial infection. The aim of the study was to investigate CgA, measured by Chromogranin A361-372 (Catestatin; Cst) and Chromogranin A17-38 (Vasostatin; VS) in healthy dogs and in dogs with pyometra.ResultsFifty dogs with pyometra, sampled prior to surgery and 64 healthy female dogs were included. In 19 pyometra cases, blood samples were also collected postoperatively. Concentrations of Cst and VS were measured in heparinised plasma and Cst also measured in EDTA plasma, by in-house radioimmunoassays. Student¿s t-test and Wilcoxon two-sample test was used to test for differences between dog groups. Pre- and postoperative samples in dogs with pyometra were analysed by paired t-test. Pearson correlation was used to investigate associations of laboratory variables and hospitalization. P < 0.05 was considered significant.Concentrations of Cst were decreased in pyometra dogs (mean ± SE, 1.01 ± 0.05 nmol/L) compared to healthy dogs (mean ± SE, 1.70 ± 0.03 nmol/L) (p ¿ 0.0001). VS concentrations did not differ significantly between dogs with pyometra (0.40 ± 0.04 nmol/L) and healthy dogs (0.42 ± 0.03 nmol/L). Mean ± SE pre- and postoperative concentration of Cst (1.0 ± 0.04 nmol/L and 0.9 ± 0.2 nmol/L) and VS (0.36 ± 0.04 nmol/L and 0.36 ± 0.04 nmol/L) in dogs with pyometra did not differ significantly. Neither Cst nor VS concentrations were associated with duration of hospitalization and were not significantly different in the four dogs with pyometra that had prolonged (¿3 d) postoperative hospitalization.ConclusionConcentrations of Cst, but not VS, were decreased in pyometra. Cst and VS concentrations before and after ovariohysterectomy did not differ significantly and were not associated with duration of hospitalization. Further studies are warranted to evaluate a possible diagnostic or prognostic value for Cst and VS.

  • 39.
    Johansson, Anders
    et al.
    Linköping Univ, Dept Behav Sci, S-58183 Linköping, Sweden.
    Odén, Anders
    Chalmers, Dept Math Sci, S-41296 Gothenburg, Sweden.
    Dahlgren, Lars-Owe
    Linkoping Univ, Dept Behav Sci, S-58183 Linkoping, Sweden.
    Sjöström, Björn
    University of Skövde, School of Life Sciences.
    A comparison of experiences of training emergency care in military exercises and competences among conscript nurses with different levels of education2007In: Military medicine, ISSN 0026-4075, Vol. 172, no 10, 1046-1052 p.Article in journal (Refereed)
    Abstract [en]

    The military emergency care education of nurses is primarily concerned with the treatment of soldiers with combat-related injuries. Even though great progress has been made in military medicine, there is still the pedagogical question of what emergency care education for military nurses should contain and how it should be taught. The aim of this study was to describe and compare experiences of training emergency care in military exercises among conscript nurses with different levels of education. A descriptive study was performed to describe and compare experiences of training emergency care in military exercises among conscript nurses with different levels of education in nursing. There were statistical differences between nurses with general nursing education and nurses with a general nursing education and supplementary education. A reasonable implication of the differences is that the curriculum must be designed differently depending on the educational background of the students. Hence, there is an interaction between background characteristics, e.g., the level of previous education and differences pertaining to clinical experience of the participants, and the impact of the exercise itself.

  • 40.
    Johansson, Jessica
    Örebro University, Department of Clinical Medicine.
    Effect of interleukin-1beta on tyrosine uptake in fibroblasts of schizophrenic patients and healthy controls2007Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    A repeated finding in schizophrenic patients is an aberrant tyrosine transport, shown in fibroblast cell model. Altered levels of the pro-inflammatory cytokine interleukin-1beta (IL-1β) are indicated in schizophrenic patients and IL-1β has shown to have inhibitory effect on amino acid transport systems. Based on these findings, the aim of this study was to examine the effect of IL-1β on tyrosine uptake in fibroblasts of schizophrenic patients and healthy controls. Fibroblast cell lines from schizophrenic patients (n=10) and healthy controls (n=10) were treated with IL-1β and uptake of 14C (U)-L-tyrosine was measured using the cluster tray method. Fibroblasts untreated with IL-1β were used as controls. Treatment with IL-1β significantly inhibited the tyrosine uptake in fibroblasts of schizophrenic patients and controls. No difference in uptake levels between fibroblasts of schizophrenic patients and controls was found. This study provides one potential explanation for the aberrant tyrosine transport seen in patients with schizophrenia and thus combines the immunological and neuropharmacological factors implicated in the pathophysiology/etiology of schizophrenia.

  • 41.
    Kask, Kristiina
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Hormones, Mood and Cognition2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ovarian steroid hormones are neuroactive steroids with widespread actions in the brain, and are thus able to influence mood, behavior and cognition.

    In this thesis the effects of progesterone withdrawal and the direct effects of the progesterone metabolite allopregnanolone are evaluated.

    Allopregnanolone, through binding to the GABAA receptor complex, enhances inhibitory neurotransmission, thus exerting anxiolytic, sedative and antiepileptic effects.

    The acoustic startle response (ASR) is a withdrawal reflex evoked by sudden or noxious auditory stimuli, and can be measured in humans as an eye blink. ASR is significantly increased in several anxiety disorders, and notably also during progesterone withdrawal.

    Sensorimotor gating can be assessed by measuring prepulse inhibition of the startle response (PPI). The CNS circuits regulating PPI are sensitive to hormone fluctuations. GABAergic drugs are involved in cognitive impairment and animal studies have indicated that allopregnanolone may inhibit learning.

    The main purpose of this research was to evaluate the behavioral effects of progesterone withdrawal on the startle response and sensorimotor gating in PMDD patients and healthy controls, in healthy third trimester pregnant women and healthy postpartum women. A second aim was to evaluate allopregnanolone effects on memory and cognition in healthy women and also on the startle response and PPI.

    We found that PMDD patients have an increased startle response across the menstrual cycle and a deficiency in sensorimotor gating during the late luteal phase.

    Ovarian steroids affect sensorimotor gating; pregnant women have lower levels of PPI than late postpartum women. Acutely administered allopregnanolone did not affect the ASR or PPI. Allopregnanolone impairs episodic memory in healthy women.

    In conclusion, our studies suggest that ovarian steroids, including allopregnanolone, do not influence the startle response. Ovarian steroids affect sensorimotor gating; pregnancy, a condition with high levels of ovarian steroids, suppresses PPI. Theoretically, the variability in PPI across reproductive events is due to effects mediated by the progesterone or estradiol receptors but is not mediated by allopregnanolone. PMDD patients display decreased PPI during the late luteal phase, suggesting underlying pathophysiology in common with other anxiety disorders. The most vulnerable memory system, the episodic memory, is impaired by the allopregnanolone in healthy women.

  • 42.
    Kernell, Kristina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Cardiac disease in pregnancy and consequences for reproductive outcomes, comorbidity and survival2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Advances in medical treatment during the last 50 years have resulted in more individuals with congenital heart disease (CHD) and Marfan syndrome reaching childbearing age. The substantial physiological changes during pregnancy result in a high-risk situation, and pregnancy is a major concern in women with these conditions.

    Aims

    • To describe the socio-demographic characteristics, birth characteristics and reproductive patterns of individuals with CHD and women with Marfan syndrome.
    • To investigate obstetric and neonatal outcomes in the firstborn children of individuals with CHD and women with Marfan syndrome.
    • To study long-term cardiovascular outcomes after childbirth in women with Marfan´syndrome.

    Methods

    The studies are population-based register studies. The study population in the first paper included all women born between 1973 and 1983 who were alive and resident in Sweden at the age of 13 (494 692 women, of whom 2 216 were women with CHD). In the second paper, the same definition of the study population was chosen, except that it involved all men born between 1973 and 1983 (522 216 men, of whom 2 689 men with CHD). The third and fourth papers involved a study population of all Swedish women born between 1973 and 1993 who were still living in Sweden at age 13. This population consisted of 1 017 538 women, 273 of whom had been diagnosed with Marfan syndrome.

    Results and conclusions

    The individuals studied were more often born preterm, and were small-for-gestational age babies. They were more likely to have been born by cesarean section. In women with CHD, these characteristics were repeated in their firstborn children. No increased risks were found in children of men with CHD or in children of women with Marfan syndrome. There was no increased risk of aortic dissection in women with Marfan syndrome during pregnancy compared to women with Marfan syndrome who did not give birth. Higher frequencies of cardiac arrhythmia and valvular heart disease were found after childbirth in women with Marfan syndrome. Pregnancy in women with CHD is a high-risk situation associated with increased risk of adverse neonatal outcomes for the expected child. Pregnancy in women without CHD, but where the father has CHD is not so associated with increased risk of adverse obstetric or neonatal outcomes. Pregnancy in women with Marfan syndrome is not associated with adverse outcomes for the expected child.

  • 43.
    Klasson, Anna
    Linköping University, Department of Medicine and Health Sciences, Radiology . Linköping University, Faculty of Health Sciences.
    MRI Contrast Enhancement using Gd2O3 Nanoparticles2008Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    There is an increasing interest for nanomaterials in biomedical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3) have been investigated as a novel contrast agent for Magnetic Resonance Imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were also investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI.

    Results show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and a distinct increase in signal intensity in T1-mapped images. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as a multimodal contrast agent.

    This study shows that Gd2O3 nanoparticles possess excellent relaxation properties that are retained in more biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in for instance cell labeling experiments.

  • 44.
    Liedberg, Gunilla
    Linköping University, Department of Social and Welfare Studies, Health, Activity, Care. Linköping University, Faculty of Health Sciences.
    Women with fibromyalgia: Employment and daily life2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: The major symptoms of fibromyalgia have been shown to severely impact everyday activities. As a consequence, many women have problems remaining in a work role. Not being able to fulfil valued roles influences quality of life. Moreover, consequences in terms of high costs in compensation for reduced work ability are also of importance for society. Today, the number of young women diagnosed with fibromyalgia is increasing.

    Objectives: The general aim of this thesis was to increase and deepen knowledge of the life situation of women with fibromyalgia; to examine how to manage a work role when in constant pain, and especially the situation for newly-diagnosed women.

    Subjects and Methods: 278 women with longstanding pain were included. The thesis includes five different studies, two of them with a focus on the work situation, two with focus on young, newly-diagnosed women’s life situation, and one investigating time-use and activity patterns in working and non-working women with fibromyalgia. Methods used are a postal questionnaire, instruments commonly used in fibromyalgia, a diary, and interviews.

    Results: Despite limitations in physical capacity, 48% of the women are working, full-time or part-time. However, most job loss is associated with the fibromyalgia symptoms, and the women report that the symptoms influence their daily activities during most of their waking time. There is a rapid increase in sickness absence in the newly-diagnosed women, and the young women in particular do not return to the labour market during the first year after receiving their diagnosis. The non-working women have a more demanding family situation, and are also less satisfied with their present situation than working women.

    Conclusion: When individual adjustments of the work situation are made and the women participate to a level that matches their ability, they are able to continue in a work role. In evaluating the women’s work capacity, the total life situation of the women should be considered.

  • 45.
    Lindehammar, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Neurophysiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurophysiology UHL.
    Muscle function in Juvenile Idiopathic Arthritis: A two-year follow-up2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This is a study of muscle function in Juvenile Idiopathic Arthritis (JIA). Rheumatoid arthritis (RA) is a disease that primarily affects the synovial membrane of joints. Muscle weakness, atrophy and pain occur in adult RA. This may be a consequence of joint pain, stiffness and immobility. Muscle inflammation and neuropathy occur as complications in adults. Muscle function in JIA has been much less studied.

    The aim of the study was to examine whether muscle weakness and atrophy also occur in children with JIA.

    This was a longitudinal study over a two-year period, where muscle strength and thickness were measured repeatedly in a group of 20 children and teenagers with JIA. Muscle strength was measured using different methods and in several muscle groups. Muscle biopsies were obtained and nerve conduction velocity studies performed.

    The study concludes that, compared to healthy people, children and teenagers with JIA have as a group reduced muscle strength and muscle thickness. For most of these children and teenagers, muscle strength is only slightly lower than expected, but a few have marked muscle weakness. This is most apparent in patients with severe polyarthritis where the weakness seems to be widespread. Patients with isolated arthritis may also have greatly reduced strength and thickness of muscles near the inflamed joint.

    There is a risk of decreasing strength in patients with polyarthritis and in muscles near an active arthritis.

    Minor changes are common in muscle biopsies, and findings may indicate immunological activity in the muscles.

    Atrophy of type II fibres, as in adult RA, was not found in JIA.

    No patient had signs of neuropathy.

  • 46.
    Lindström, Meta
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Gynekologer och barnmorskor inom svensk abortvård: åsikter, erfarenheter och upplevelser2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aim: To investigate gynecologists’ and midwives’ views and experiences regarding work in abortion care in Sweden.

    Methods: Questionnaire to gynecologists (n=269) and midwives (n=258 comprising 48 questions, response 85%. The quantitative studies (articles I-III) were supplemented by a qualitative study (article IV), consisting of focus-group interviews with gynecologists and midwives/nurses.

    Results: From the questionnaire studies it was apparent that all the gynecologists had worked in abortion care, whilst not all midwives had done so. The male gynecologists were older than both their female colleagues and the midwives; they had most years of experience but were now working least with abortion patients. Both groups considered it absolutely right, that Sweden have legal abortion and that the law was being followed. Most thought that women should be allowed to have an abortion even after they had felt fetal movements. The midwives were generally somewhat more restrictive than the gynecologists. Half of all thought that the work with abortion patients brought something positive with it. Those having worked longest and most extensively, especially during the previous year were most liberal. Both groups felt that there was a difference between working with surgical and late abortions compared with medical abortions. One in four had had misgivings when involved in surgical and medical abortions, and one in two with abortions after the 18th week. All were positive about the transition to medical abortions, and roughly two thirds of the midwives thought that the primary care sector should be able to take care of these, whereas less than half of the gynecologists thought this. The majority considered it important to receive further and continuing professional development and ongoing guidance. From the focus-group interviews it was clear that the experiences of the gynecologists were largely connected with the technical development of abortion methods and those of the midwives/nurses with improved pain relief. The work was sometimes described in paradoxical terms and was occasionally experienced as frustrating, especially in connection with repeat abortions. Neither of the two groups, however, had had any doubts about participating in abortion. The gynecologists described how women now expected to get an abortion, whereas previously they had asked for one. The midwife/nurse group maintained that the meetings with the women had become considerably more frequent. The interaction between the two professional groups was marked by great trust in each other’s professional competence.

    Conclusions: Gynecologists and midwives working in abortion care support Swedish abortion legislation and have no doubts about participating in abortions, despite the fact that they have frequently experienced complex and difficult work situations. The character of the work is experienced as contradictory and frustrating, but also as challenging and rewarding. The awareness that the two professional groups have of the importance of continuing professional development and ongoing guidance should be acted on. Furthermore, their collective views and experiences should be made use of, so that abortion care can be developed, not only in order to promote women’s health, but also to improve the work environment for the abortion staff.

  • 47.
    Lundgren, Magdalena
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Interplay between hormones, nutrients and adipose depots in the regulation of insulin sensitivity: an experimental study in rat and human adipocytes2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Obesity and specifically central obesity is related to insulin resistance, type 2 diabetes and other components of the so-called metabolic syndrome. The aim of this study was to elucidate the interplay between hormones, nutrients and adipose depots in normal and insulin-resistant fat cell metabolism.

    High levels of free fatty acids (FFAs) induce insulin resistance in muscle and liver in vivo. In the present study, rat adipocytes were treated with high physiological levels of oleic or palmitic acid in vitro for 4-24 h. This treatment had no effect on basal or insulin-stimulated glucose uptake capacity in these cells, neither did it affect the levels of the insulin signalling proteins; insulin receptor substrate (IRS)-1 or –2, phosphatidylinositol 3-kinase (PI3-K), protein kinase B (PKB) or glucose transporter (GLUT) 4, or the regulation of lipolysis rate.

    Visceral adiposity is considered to be more harmful than peripheral adiposity with respect to metabolic and cardiovascular complications. In adipose biopsies from subjects undergoing abdominal surgery, we found that glucose uptake capacity was elevated in omental as compared to subcutaneous adipocytes. The sensitivity (EC50) or maximum relative response to insulin, measured as % of basal, did however not differ between the depots. In women, subcutaneous adipocytes displayed a higher lipolysis rate following cAMP-stimulation than omental adipocytes, whereas there was a tendency towards the opposite in adipocytes from men. No differences were found between depots or sexes in the ability of insulin to inhibit lipolysis or in the levels of the lipolysis regulating proteins, i.e. protein kinase A (PKA), hormone sensitive lipase (HSL) and perilipin.

    Glucocorticoids, e.g. cortisol, exert pronounced insulin-antagonistic effects and are associated with redistribution of fat from peripheral to central fat depots in humans. Treatment of human subcutaneous and omental adipocytes in vitro, with the cortisol analogue dexamethasone, resulted in a dose dependent down-regulation of basal and insulin-stimulated glucose uptake capacity in omental, but not in subcutaneous cells. Concomitantly, the levels of IRS-1 and PKB were decreased only in omental adipocytes after dexamethasone treatment. The relative effect of insulin to stimulate glucose uptake was however not altered by dexamethasone treatment. The cAMP-stimulated lipolysis rate was elevated by dexamethasone treatment in cells from the subcutaneous depot in women and tended to be elevated in omental cells from men. No alterations however, were seen in the levels of the assessed lipolysis regulating proteins.

    Subcutaneous as well as omental fat cell size correlated negatively to insulin action in subcutaneous fat cells in vitro after adjusting for age, sex and body fat parameters in non-diabetic, but not in type 2 diabetic, subjects. Large subcutaneous fat cell size was strongly related to plasma leptin levels in non-diabetic and in type 2 diabetic subjects.

    We conclude that 1) adipocytes seem to be less vulnerable to elevated levels of fatty acids than muscle and liver cells, 2) the interactions between glucocorticoids and insulin in the regulation of glucose uptake differ between adipose depots, 3) depot specific hormonal lipolysis regulation differs between sexes and 4) fat cell size is related to insulin action in subcutaneous fat cells and to circulating levels of leptin.

  • 48.
    Löfgren, Magnus
    Umeå University, Faculty of Medicine, Clinical Sciences, Obstetrics and Gynaecology.
    Behavioral effects of female sex steroid hormones : models of PMS and PMDD in Wistar rats2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Animal models can be used to mimic human conditions of psychopathology, and also as pre-clinical models to evaluate candidate drugs. With hormonal treatment it is possible to produce behavior in the rat which corresponds to the mental symptoms of pre-menstrual syndrome (PMS), and pre-menstrual dysphoric disorder (PMDD). PMS affects 25-30 % of all women in fertile age and 3-8% are diagnosed with the more severe condition PMDD. The cardinal mental symptoms are; irritability, mood-swings, depression, anxiety, fatigue, insomnia, difficulties with concentration and memory and learning difficulties. The symptoms of PMS/PMDD occur in the luteal phase in conjunction with increasing concentrations of progesterone (P4) and P4-metabolites. In anovulatory cycles the symptoms are absent. The hormones which produce the monthly reoccurring negative symptoms on mood are foremost the neuroactive metabolites; allopregnanolone (ALLO) and tetrahydro-deoxycorticosterone (THDOC). ALLO is produced by the corpus luteum, but can also be synthesized in the brain, both ALLO and THDOC can also be released from the adrenal cortex during stress. These steroids are active on the inhibitory GABA neurotransmitter system through the GABAA receptor, and the effects are similar to that of alcohol and benzodiazepines. These steroids have strong sedative and hypnotic effects. A paradox is that some individuals seem to react with negative mood on sex steroids while all fertile women have the cyclical steroid changes during the menstrual cycle. Some individuals are more sensitive to neuroactive steroids with influences of personality, heritability and stress factors.

    Aims The thesis aims were to develop pre-clinical animal models of PMS/PMDD and to investigate induction of ALLO tolerance, individual sensitivity to neurosteroids and the interactions between chronic social stress and neurosteroids.

    Methods In these studies male and female Wistar rats were used to test steroid hormone effects on learning and memory and behaviors analogous to negative mood symptoms. This was accomplished through hormonal treatment and a subsequent withdrawal period from P4 (P4) + estradiol (E2) (PEWD), or ALLO. To assess tolerance, memory and learning in the Morris water maze (MWM) was studied. Anxiety-like behaviors were tested with the elevated plus maze (EPM), open field test (OFT), and the intruder test (IT). The EPM or OFT was used to classify the rats as high or low responders on risk-taking and explorative behavior (HR/LR). For social ranking order assessment the tube test (TT) and food competition test (FCT) were used. Chronic social stress was accomplished through co-habituation with two older rats (chronic subordination stress). In female rats the estrous cycle followed using staining of vaginal smears. Concentration of corticosterone (CORT) was measured by radio-immuno-assay (RIA).

    Results In the MWM ALLO pre-treatment produced tolerance to the acute negative ALLO effects. Both male and female rats showed behavioral correlations between the EPM and OFT tests, and correlations were also seen in CORT levels. Individuals with the stable trait of high risk-taking and explorative behavior (HR) were more sensitive to PEWD induction of anxiety-like behavior. These animals also showed decreased CORT levels during withdrawal. Chronic subordination stress enhanced the response to PEWD on measures of locomotor activity and social anxiety-like behavior.

    Conclusions It is possible to induce tolerance to the negative ALLO effects on learning and memory. The animal models of anxiety-like behavior show an individual PEWD response profile where HR rats are more sensitive. Exposure to chronic social stress enhanced the PEWD response. Hence there are both inherent and environmental factors behind the behavioral response to steroid hormones in rats.

  • 49.
    Löfgren, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Johansson, Inga-Maj
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Strömberg, Jessica
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Meyerson, Bengt
    Department of Neuroscience, Division of Pharmacology, Box 593, BMC, SE-751 24 Uppsala, Sweden..
    Bäcktröm, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Chronic subordination stress augments combined progesterone and estradiol withdrawal behaviorManuscript (Other academic)
    Abstract [en]

    Exposure to stress is a risk factor for developing pre-menstrual syndrome (PMS) and pre-menstrual dysphoric disorder (PMDD), and stress enhances the anxiogenic effect of female sex steroids in animals. This study examines the interaction between chronic subordination stress and withdrawal from progesterone (P4) and estradiol (E2) (PEWD) in producing behaviors analogous to anxiety and irritability in rats. At the start of the experiment, male Wistar rats were housed in triads consisting of one younger rat (~35 days) and two older rats (~50 days). The housing condition was aimed at producing chronic subordination stress in the younger animals. Chronic subordination stress was assessed by the elevated plus maze (EPM) and by corticosterone (CORT) analysis. A triad of three 35-day-old rats was used as age control. Social rank within the triads was determined using a food competition test (FCT) and the tube test (TT). The younger rats (subordinate) and the dominant rats were assigned to 10 days of treatment with 5 mg/kg progesterone combined with 10 µg/kg 17β estradiol. Twenty-four hours after the last injection, the subordinate and dominant animals were tested in the open-field test (OFT) and in the intruder test (IT). The IT consists of a 10-minute exposure to 3 unfamiliar rats. Chronic subordination stress reduced EPM open-arm time and altered the CORT response. It also made the subordinate animals more vulnerable to PEWD. The effects were increased locomotion in the OFT, increased defensive burying, and increased social anxiety in the intruder test (IT). Dominant animals did not react to PEWD. Thus, chronic subordination stress augments PEWD.

  • 50.
    Lönnqvist, Susanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Applications of human skin in vitro2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Chronic wounds are a substantial problem in today’s health care and place significant strains on the patient. Successful modelling of the wound healing process is pivotal for the advancement of wound treatment research. Wound healing is a dynamic and multifactorial process involving all constituents of the skin. The progression from haemostasis and inflammation to proliferation of epidermal  keratinocytes and dermal fibroblasts, and final scar maturation can be halted and result in a chronic wound that fails to re-epithelialise. The wound healing process constitutes an example of dynamic reciprocity in tissue where cellular changes take place on cues from the extracellular matrix and vice versa when tissue homeostasis is disturbed. The extracellular matrix provides a structural context for the resident cells and the epidermal keratinocytes, and a functioning interplay between the two tissue compartments is crucial for successful wound healing to take place. Work included in this thesis has applied viable human full thickness skin in vitro to investigate the re-epithelialisation process and barrier function of intact skin.The use of full thickness skin in vitro can take into account the contextual aspect of the process where the epidermal keratinocytes are activated and obtain a migratory phenotype, and are continuously dependent on the cues from the extracellular matrix and support of the dermis. When utilising skin for studies on re-epithelialisation, circular standardised full thickness wounds were created and cultured  for up to four weeks in tissue culture. In paper I, the organisation of a thick neoepidermis was investigated in the in vitro wound healing model when resident cells were provided with a porous suspended three dimensional gelatin scaffold. In paper II we investigated the use of a fluorescent staining conventionally used for proliferation studies to facilitate the tracing of transplanted epidermal cells in in vitro  wounds, in order to improve and expand the use of the model. In paper III the model was utilised to investigate the treatment approach of acidification of wounds to evaluate the suitability of such intervention in regards to keratinocyte function and re-epithelialisation. Studies on re-epithelialisation with the aid of the in vitro wound healing model provided insight in neoepidermal structure with porous gelatin scaffolding in the wound, a novel methodological approach to tracing cells and response to constrained wound healing environment. In paper IV, intact human skin was evaluated for modelling the cytotoxic response after exposure to a known irritant compound. To study barrier function, intact skin was exposed to irritants by restricting exposure topically, and full thickness skin in vitro was found suitable for modelling cytotoxicity responses. Employing human full thickness skin in vitro makes use of the actual target tissue of interest with epidermal and dermal cells, and full barrier function.

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