| 1. |
- Nääv, Åsa, et al.
(författare)
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A1M Ameliorates Preeclampsia-Like Symptoms in Placenta and Kidney Induced by Cell-Free Fetal Hemoglobin in Rabbit.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is one of the most serious pregnancy-related diseases and clinically manifests as hypertension and proteinuria after 20 gestational weeks. The worldwide prevalence is 3-8% of pregnancies, making it the most common cause of maternal and fetal morbidity and mortality. Preeclampsia lacks an effective therapy, and the only "cure" is delivery. We have previously shown that increased synthesis and accumulation of cell-free fetal hemoglobin (HbF) in the placenta is important in the pathophysiology of preeclampsia. Extracellular hemoglobin (Hb) and its metabolites induce oxidative stress, which may lead to acute renal failure and vascular dysfunction seen in preeclampsia. The human endogenous protein, α1-microglobulin (A1M), removes cell-free heme-groups and induces natural tissue repair mechanisms. Exogenously administered A1M has been shown to alleviate the effects of Hb-induced oxidative stress in rat kidneys. Here we attempted to establish an animal model mimicking the human symptoms at stage two of preeclampsia by administering species-specific cell-free HbF starting mid-gestation until term, and evaluated the therapeutic effect of A1M on the induced symptoms. Female pregnant rabbits received HbF infusions i.v. with or without A1M every second day from gestational day 20. The HbF-infused animals developed proteinuria and a significantly increased glomerular sieving coefficient in kidney that was ameliorated by co-administration of A1M. Transmission electron microscopy analysis of kidney and placenta showed both intracellular and extracellular tissue damages after HbF-treatment, while A1M co-administration resulted in a significant reduction of the structural and cellular changes. Neither of the HbF-treated animals displayed any changes in blood pressure during pregnancy. In conclusion, infusion of cell-free HbF in the pregnant rabbits induced tissue damage and organ failure similar to those seen in preeclampsia, and was restored by co-administration of A1M. This study provides preclinical evidence supporting further examination of A1M as a potential new therapy for preeclampsia.
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| 2. |
- Wester, Agneta, et al.
(författare)
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Caregivers’ experiences of caring for an elderly next of kin in Sweden
- 2013
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Ingår i: Vård i Norden. - 0107-4083 .- 1890-4238. ; 33:4, s. 28-32
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Tidskriftsartikel (refereegranskat)abstract
- Background: Care of elderly changed in the 1990s in Sweden; treatment sessions were shortened in particular. Consequently, patients have a greater need for care when returning home from hospital. This task may seem overwhelming and caregivers can feel lonely, worn out and resigned in their situation. Aim: Explore how caregivers experience caring for an elderly next of kin in ordinary living. Method: Qualitative content analysis of semi-structured interviews with eleven Swedish caregivers. Findings: Caregivers experienced their situation as something to be endured. In particular, they felt a need for belonging, a need for controlling everyday life, and a need for support. Conclusion: Home care nurses, health centres and home support workers should be aware of and respect caregivers’ needs in terms of support.
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| 5. |
- Bråndal, Anna, 1966-
(författare)
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Rehabilitation after stroke with focus on early supported discharge and post-stroke fatigue
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Stroke is a major cause of disability worldwide. After treatment in a specialized stroke unit, early supported discharge (ESD) followed by home rehabilitation has shown to be an effective way to improve patient outcome and quality of care for persons with mild to moderate stroke. ESD service is recommended in the national and international guidelines for stroke care, but has only partially been implemented in Sweden. Following stroke, fatigue is a common consequence that often becomes more evident when the patient comes home. Currently, there is insufficient evidence about how to measure, treat and handle post-stroke fatigue. The overall aim of this thesis was to evaluate and implement early supported discharge (ESD) based on stroke patients experience after discharge from the stroke unit and local conditions. The aim was also to evaluate post-stroke fatigue with a potentially valid and reliable scale and finally to prepare for a study to evaluate cardiorespiratory training as a part of ESD service for patients with post-stroke fatigue.Methods In paper I, nine strategically chosen patients were interviewed of their experience of falling ill, the hospital stay, discharge, contact with health care after discharge and their request of support. Papers II-III describe and evaluate the development, content, implementation and effects of a locally adopted method for early supported discharge (Umeå Stroke Center ESD) in modern stroke care. Paper II included 153 consecutive patients and paper III, 30 232 patients with first-ever stroke registered in the Riksstroke registry in Sweden. Paper II evaluated number of patients/year, clinical and functional health status, satisfaction in relation to needs, accidental falls/other injuries and resources with the result summarized in a value compass. The implementation process was evaluated retrospectively by means of Consolidated Framework for Implementation (CFIR). Paper III evaluated patient reported outcome measurements (PROMs) at 3 months. The primary outcome in paper III was satisfaction with the rehabilitation after discharge. Secondary outcomes were information about stroke provided, tiredness/fatigue, pain, dysthymia/depression, general health status and dependence in activities of daily living (mobility, toilet hygiene and dressing). Multivariable logistic regression models for each PROM was used to analyze associations between PROMs and ESD/no ESD. In Paper IV, the Fatigue Assessment scale (FAS) was translated into Swedish and evaluated regarding psychometric properties when self-administered by persons with mild to moderate stroke. 72 consecutively patients selected from the stroke unit admission register received a letter including three questionnaires: the FAS, the Short Form Health Survey (SF-36) subscale for vitality and the Geriatric Depression Scale GDS-15. A second letter with FAS was sent within 2 weeks, for re-test evaluation. Paper V is a study protocol for a planned randomized controlled trial (RCT) of 50 consecutive stroke patients will who receive stroke unit care followed by ESD-service at Umeå Stroke Center, University Hospital, Umeå, Sweden. Paper V will investigate if a structured cardiorespiratory interval training program (CITP) added to the ESD-service may result in relieved post-stroke fatigue and increased oxygen uptake.Results The interviews in Paper I revealed three main categories with subcategories: “Responsible and implicated”, “Depersonalized object for caring measures” and “The striving for repersonalization and autonomy”. The findings indicate that coming home gave the informants’ important insights and understanding of the stroke, its consequences and was also an important factor for the recovery. Paper II-III showed that it is possible to develop and implement an adapted ESD service for stroke patients based on the patients’ experiences and requests, evidence-based recommendations and local conditions. The ESD service reduced dependence of activity, increased mobility with seemingly no increased risk of accidental falls or other injuries. The patient satisfaction in relation to needs regarding the ESD was high. Paper III showed that patients that received ESD were more satisfied with rehabilitation after discharge, had less need for assistance with ADL and less dysthymia/depression compared to patients that did not receive ESD. Study IV showed that the Swedish FAS used at home as a selfadministered questionnaire is a reliable and valid questionnaire for measuring fatigue in persons with mild to moderate stroke. The internal consistency was good, the agreement between the test and retest reliability for individual items (weighted kappa) was for the majority of items good or moderate. The relative reliability for total scores was good and the absolute reliability was 9 points. The Swedish FAS had no floor nor ceiling effects and correlated both with the SF-36, subscale for vitality and the GDS-15 indicating convergent construct validity, but not divergent construct validity.Conclusion It is possible to develop and implement ESD care for stroke patients based on patients’ experience and needs, evidence-based principles and local conditions. Early supported discharge (ESD) in the setting of modern stroke unit care appears to have positive effects on rehabilitation in the subacute phase. The Swedish FAS used at home as a self-administered questionnaire is reliable and valid for measuring fatigue in persons with mild to moderate stroke.
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| 6. |
- Falkenberg, Cecilia, et al.
(författare)
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Expression of a functional proteinase inhibitor capable of accepting xylose: bikunin
- 2001
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Ingår i: Archives of Biochemistry and Biophysics. - : Elsevier BV. - 0003-9861. ; 387:1, s. 99-106
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Tidskriftsartikel (refereegranskat)abstract
- Bikunin is a Kunitz-type proteinase inhibitor, which is cross-linked to heavy chains via a chondroitin sulfate chain, forming inter-alpha-inhibitor and related molecules. Rat bikunin was produced by baculovirus-infected insect cells. The protein could be purified with a total yield of 20 mg/liter medium. Unlike naturally occuring bikunin the recombinant protein had no galactosaminoglycan chain. Endoglycosidase digestion also suggested that the recombinant form lacked N-linked oligosaccharides. Bikunin is translated as a part of a precursor, alpha1-microglobulin/bikunin, but the functional significance of the cotranslation is unknown. Our results indicate that the proteinase inhibitory function of bikunin is not regulated by the alpha1-microglobulin-part of the alpha1-microglobulin/bikunin precursor since recombinant bikunin had the same trypsin inhibitory activity as the recombinant precursor. Both free bikunin and the precursor were also functional as a substrate in an in vitro xylosylation system. This demonstrates that the alpha1-microglobulin-part is not necessary for the first step of galactosaminoglycan assembly.
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| 7. |
- Gedda, Lars, et al.
(författare)
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Evaluation of Real-Time Immunohistochemistry and Interaction Map as an Alternative Objective Assessment of HER2 Expression in Human Breast Cancer Tissue
- 2013
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Ingår i: Applied immunohistochemistry & molecular morphology (Print). - 1541-2016 .- 1533-4058. ; 21:6, s. 497-505
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Tidskriftsartikel (refereegranskat)abstract
- Immunohistochemical study (IHC) is a critical tool in the clinical diagnosis of breast cancer. One common assessment is the expression level of the HER2 receptor in breast cancer tissue samples with the aim of stratifying patients for applicability of the therapeutic antibody Herceptin. In this study, we aimed to investigate whether a novel assay, real-time IHC combined with Interaction Map analysis, offers the possibility of objective assessment of HER2 expression. Interaction Map presents real-time interaction data as a collection of peaks on a surface, and it was performed on 20 patient tissue samples previously scored for HER2 expression. The result shows that the relative weight of the peaks in the maps contains novel information that could discriminate between high and low HER2 expression in an operator-independent manner (P<0.001). We conclude that the real-time IHC assay has a promising potential to complement conventional IHC and may improve the precision in the future clinical diagnostics of breast cancer.
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| 8. |
- Gram, Magnus, et al.
(författare)
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The radical-binding lipocalin A1M binds to a Complex I subunit and protects mitochondrial structure and function.
- 2013
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Ingår i: Antioxidants & Redox Signaling. - : Mary Ann Liebert Inc. - 1557-7716 .- 1523-0864. ; 18:16, s. 2017-2028
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Tidskriftsartikel (refereegranskat)abstract
- Aims: During cell death, energy-consuming cell degradation and recycling programs are performed. Maintenance of energy-delivery during cell death is therefore crucial but the mechanisms to keep the mitochondrial functions intact during these processes are poorly understood. We have investigated the hypothesis that the heme- and radical-binding ubiquitous protein A1M (α1-microglobulin) is involved in protection of the mitochondria against oxidative insult during cell death. Results: Using blood cells, keratinocytes and liver cells, we show that A1M binds with high affinity to apoptosis-induced cells and is localized to mitochondria. The mitochondrial Complex I subunit NDUFAB1 was identified as a major molecular target of the A1M-binding. Furthermore, A1M was shown to inhibit the swelling of mitochondria, and to reverse the severely abrogated ATP-production of mitochondria when exposed to heme and ROS. Innovation: Import of the radical- and heme-binding protein A1M from the extracellular compartment confers protection of mitochondrial structure and function during cellular insult. Conclusion: A1M binds to a subunit of Complex I and has a role in assisting the mitochondria to maintain its energy delivery during cell death. A1M may also, at the same time, counteract and eliminate the ROS generated by the mitochondrial respiration to prevent oxidative damage to surrounding healthy tissue.
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| 9. |
- Holmdahl, Rikard, et al.
(författare)
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Arthritis induced in rats with non-immunogenic adjuvants as models for rheumatoid arthritis
- 2001
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Ingår i: Immunological Reviews. - : Wiley. - 1600-065X .- 0105-2896. ; 184
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Forskningsöversikt (refereegranskat)abstract
- Rat models are useful for studies of the pathogenesis of rheumatoid arthritis (RA) since rats are extraordinarily sensitive to induction of arthritis with adjuvants. Injection of not only the classical complete Freund's adjuvant but also mineral oil without mycobacteria and pure adjuvants such as pristane and squalene, induce severe arthritis in many rat strains. Models like pristane-induced arthritis in rats are optimal models for RA since they fulfill the RA criteria including a chronic relapsing disease course. Arthritogenic adjuvants like pristane, avridine, squalene and mineral oil are not immunogenic since they do not contain major histocompatibility complex (MHC) binding peptides. Nevertheless, the diseases are MHC-associated and dependent on the activation of alphabetaTCR (T-cell receptor)-expressing T cells. However, it has not been possible to link the immune response to joint antigens or other endogenous components although immunization with various cartilage proteins induce arthritis but with different pathogeneses. To unravel the mechanisms behind adjuvant-induced arthritis, a disease-oriented genetic approach is optimal. Several loci that control onset of arthritis, severity and chronicity of the disease have been identified in genetic crosses and most of these have been confirmed in congenic strains. In addition, many of these loci are found in other autoimmune models in the rat as well as associated with arthritis in mice and humans.
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| 10. |
- Hägglund, Patricia, et al.
(författare)
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Older people with swallowing dysfunction and poor oral health are at greater risk of early death
- 2019
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Ingår i: Community Dentistry and Oral Epidemiology. - : John Wiley & Sons. - 0301-5661 .- 1600-0528. ; 47:6, s. 494-501
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We investigated the associations between swallowing dysfunction, poor oral health and mortality among older people in intermediate care in Sweden.Methods: This prospective cohort study investigated 391 older people in 36 intermediate care units (clusters). Swallowing function was assessed with the timed water swallow test (TWST), and oral health with the revised oral assessment guide (ROAG) at baseline. Data were collected on age, sex, education level, multimorbidity, cognitive impairment, care dependency and body mass index (BMI). Time to mortality was recorded during the following year. The mixed effects Cox regression model with cluster as a random factor was used to estimate hazards ratios (HR) with 95% confidence intervals (CI).Results: The median age of the participants was 84 years (interquartile range [IQR]: 11), and 53.3% were females. Mortality within one year was 25.1%. In the adjusted model, swallowing dysfunction and poor oral health were both independently associated with mortality (adjusted HR [aHR]: 1.67, 95% CI 1.02‐2.75; P = .041 and aHR: 1.98, 95% CI 1.07‐3.65; P = .029, respectively). Participants with combined swallowing dysfunction and poor oral health showed the highest mortality (35.0%) and 2.6 (95% CI 1.15‐5.89; P = .022) times higher mortality risk than those with normal swallowing function and good oral health (13.0%).Conclusions: Swallowing dysfunction and poor oral health were identified as independent risk factors for mortality in older people in intermediate care. Although further studies are required to verify these findings, they suggest that systematic assessment of swallowing function and oral health status should be performed for care considerations.
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