| 1. |
- Fakhrai-Rad, H, et al.
(författare)
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Insulin-degrading enzyme identified as a candidate diabetes susceptibility gene in GK rats.
- 2000
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 9:14, s. 2149-58
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Tidskriftsartikel (refereegranskat)abstract
- Genetic analysis of the diabetic GK rat has revealed several diabetes susceptibility loci. Congenic strains have been established for the major diabetes locus, Niddm1, by transfer of GK alleles onto the genome of the normoglycemic F344 rat. Niddm1 was dissected into two subloci, physically separated in the congenic strains Niddm1b and Niddm1i, each with at least one disease susceptibility gene. Here we have mapped Niddm1b to 1 cM by genetic and pathophysiological characterization of new congenic substrains for the locus. The gene encoding insulin-degrading enzyme (IDE:) was located to this 1 cM region, and the two amino acid substitutions (H18R and A890V) identified in the GK allele reduced insulin-degrading activity by 31% in transfected cells. However, when the H18R and A890V variants were studied separately, no effects were observed, demonstrating a synergistic effect of the two variants on insulin degradation. No effect on insulin degradation was observed in cell lysates, indicating that the effect is coupled to receptor-mediated internalization of insulin. Congenic rats with the IDE: GK allele displayed post-prandial hyperglycemia, reduced lipogenesis in fat cells, blunted insulin-stimulated glucose transmembrane uptake and reduced insulin degradation in isolated muscle. Analysis of additional rat strains demonstrated that the dysfunctional IDE: allele was unique to GK. These data point to an important role for IDE: in the diabetic phenotype in GK.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Fernström, Elisabeth A.C., et al.
(författare)
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Alterations in shoulder muscle activity due to changes in data entry organisation
- 1999
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Ingår i: International Journal of Industrial Ergonomics. - 0169-8141 .- 1872-8219. ; 23:3, s. 231-240
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate how changed work organisation and different work tasks influence shoulder muscular load and to quantify the magnitude, duration and frequency of rest periods from shoulder muscular load during a working day. Shoulder muscular load was measured in 22 females working at their data entry workplaces, during a whole working day. The activity from both trapezius muscles was measured with EMG before (1991) and after (1992) a reorganisation programme intended to redistribute repetitive work and provide new work tasks.The change in work organisation did not change the magnitude of muscular load or the duration and frequency of rest periods, but decreased musculoskeletal problems. The subjects' increased desk work involved greater muscular load than the data entry did, but also allowed more movement. The changes in work tasks seemed to be important, although small. In repetitive work, organisational changes aimed at reducing musculoskeletal disorders should focus on providing employees with tasks that afford variation in muscular load. Relevance to industry. The paper discusses the need of physical work task variation in repetitive work in order to minimise the risk of musculoskeletal disorders. It seems more important to vary the tasks than to minimise the shoulder muscular load. Copyright
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| 6. |
- Fernström, E A, et al.
(författare)
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Upper-arm elevation during office work.
- 1996
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 39:10, s. 1221-30
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Tidskriftsartikel (refereegranskat)abstract
- The present aim was to measure and quantify upper-arm elevation and to find how changed work organization and work tasks influence arm movement during a working day. Sixteen female office workers participated in the study. Their main work was statistical data entry. Upper-arm elevation was measured on two occasions separated by 18 months, i.e., before and after a change of work organization. The measurements were performed during the whole of one ordinary working day. The differences between the two measurements were mostly non-significant. Arm elevation remained essentially below 30 degrees during the main time of the working day, and the subjects worked with limited arm movements. Despite new alternative office tasks, they did not achieve a change in their habitual arm postures, or in their neck-and-shoulder disorders.
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| 7. |
- Fernström, Johan, et al.
(författare)
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Blood-based mitochondrial respiratory chain function in major depression
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction has been implicated in major depressive disorder (MDD). A measure of mitochondrial respiratory chain (RC) enzymatic activity—the Mitochondrial Health Index (MHI)—has previously been found to correlate with stress and emotional states in caregivers. We here report mitochondrial RC activities, mitochondrial DNA copy number (mtDNAcn), and the composite MHI in unmedicated and somatically healthy subjects with MDD (n = 47) and healthy controls (HC) (n = 11). We also explore, in a subset of the MDD sample (n = 33), whether these markers are associated with response to 8 weeks of SSRI treatment. Mitochondrial RC complexes I, II, IV, citrate synthase (CS), mtDNAcn, and the MHI were assayed in peripheral blood mononuclear cells. Treatment response was defined as >50% decrease on the 25-item Hamilton Depression Rating Scale (HRDS-25). There were no significant differences in MHI or any of the mitochondrial markers between MDD subjects and HCs. Compared to SSRI nonresponders, SSRI responders had significantly higher baseline mitochondrial content markers CS (p = 0.02) and mtDNAcn (p = 0.02), and higher complex I activity (p = 0.01). Complex II activity increased significantly over treatment, irrespective of clinical response (p = 0.03). Complex I activity decreased in responders (n = 9), but increased in nonresponders (n = 18) (group x time interaction, p = 0.02). Absolute treatment-associated change in HDRS-25 scores correlated significantly with change in complex I activity between baseline and week 8 (r = 0.47, p = 0.01). Although mitochondrial markers did not distinguish MDD from controls, they did distinguish SSRI responders from nonresponders. If larger studies validate these mitochondrial differences, they may become useful biomarkers and identify new drug targets.
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| 8. |
- Hjeltnes, N, et al.
(författare)
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Regulation of UCP2 and UCP3 by muscle disuse and physical activity in tetraplegic subjects.
- 1999
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 42:7, s. 826-30
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: The regulation of uncoupling protein 2 and uncoupling protein 3 gene expression in skeletal muscle has recently been the focus of intense interest. Our aim was to determine expression of uncoupling protein 2 and 3 in skeletal muscle from tetraplegic subjects, a condition representing profound muscle inactivity. Thereafter we determined whether exercise training would modify expression of these genes in skeletal muscle.METHODS: mRNA expression of uncoupling protein 2 and 3 was determined using quantitative reverse transcription-polymerase chain-reaction.RESULTS: Expression of uncoupling protein 2 and 3 mRNA was increased in skeletal muscle from tetraplegic compared with able-bodied subjects (3.7-fold p < 0.01 and 4.1-fold, p < 0.05, respectively). A subgroup of four tetraplegic subjects underwent an 8-week exercise programme consisting of electrically-stimulated leg cycling (ESLC, 7 ESLC sessions/week). This training protocol leads to increases in whole body insulin-stimulated glucose uptake and expression of genes involved in glucose metabolism in skeletal muscle from tetraplegic subjects. After ESLC training, uncoupling protein 2 expression was reduced by 62% and was similar to that in able-bodied people. Similarly, ESLC training was associated with a reduction of uncoupling protein 3 expression in skeletal muscle from three of four tetraplegic subjects, however, post-exercise levels remained increased compared with able-bodied subjects.CONCLUSION/INTERPRETATION: Tetraplegia is associated with increased mRNA expression of uncoupling protein 2 and 3 in skeletal muscle. Exercise training leads to normalisation of uncoupling protein 2 expression in tetraplegic subjects. Muscle disuse and physical activity appear to be powerful regulators of uncoupling protein 2 and 3 expression in human skeletal muscle.
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| 9. |
- Indurain, A, et al.
(författare)
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Uremic klåda
- 2010
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Ingår i: Incitament. - 1103-503X.
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 10. |
- Lindqvist, D., et al.
(författare)
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Increased plasma levels of circulating cell-free mitochondrial DNA in suicide attempters : associations with HPA-axis hyperactivity
- 2016
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major depressive disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood; however, no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls. We hypothesized that free circulating mtDNA would be elevated in the suicide attempters and would be associated with hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity. Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared with healthy controls at different time points (pre- and post-DST; all P-values < 2.98E - 12, Cohen's d ranging from 2.55 to 4.01). Pre-DST plasma levels of mtDNA were positively correlated with post-DST cortisol levels (rho = 0.49, P < 0.003). Suicide attempters may have elevated plasma levels of free-circulating mtDNA, which are related to impaired HPA-axis negative feedback. This peripheral index is consistent with an increased cellular or mitochondrial damage. The specific cells and tissues contributing to plasma levels of free-circulating mtDNA are not known, as is the specificity of this finding for suicide attempters. Future studies are needed in order to better understand the relevance of increased free-circulating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression.
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| 11. |
- Song, X M, et al.
(författare)
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5-Aminoimidazole-4-carboxamide ribonucleoside treatment improves glucose homeostasis in insulin-resistant diabetic (ob/ob) mice.
- 2002
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Ingår i: Diabetologia. - 0012-186X .- 1432-0428. ; 45:1, s. 56-65
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: The 5'AMP-activated protein kinase is an important mediator of muscle contraction-induced glucose transport and a target for pharmacological treatment of Type II (non-insulin-dependent) diabetes mellitus. The 5'AMP-activated protein kinase can be activated by 5-aminoimidazole-4-carboxamide ribonucleoside. We hypothesised that 5-aminoimidazole-4-carboxamide ribonucleoside treatment could restore glucose homeostasis in ob/ob mice.METHODS: Lean and ob/ob mice were given 5-aminoimidazole-4-carboxamide ribonucleoside (1 mg.g body wt(-1).day(-1) s.c) or 0.9 % NaCl (vehicle) for 1-7 days.RESULTS: Short-term 5-aminoimidazole-4-carboxamide ribonucleoside treatment normalised glucose concentrations in ob/ob mice within 1 h, with effects persisting over 4 h. After 1 week of daily injections, 5-aminoimidazole-4-carboxamide ribonucleoside treatment corrected hyperglycaemia, improved glucose tolerance, and increased GLUT4 and hexokinase II protein expression in skeletal muscle, but had deleterious effects on plasma non-esterified fatty acids and triglycerides. Treatment with 5-aminoimidazole-4-carboxamide ribonucleoside increased liver glycogen in fasted and fed ob/ob mice and muscle glycogen in fasted, but not fed ob/ob and lean mice. Defects in insulin-stimulated phosphatidylinositol 3-kinase and glucose transport in skeletal muscle from ob/ob mice were not corrected by 5-aminoimidazole-4-carboxamide ribonucleoside treatment. While ex vivo insulin-stimulated glucose transport was reduced in isolated muscle from ob/ob mice, the 5-aminoimidazole-4-carboxamide ribonucleoside stimulated response was normal.CONCLUSION/INTERPRETATION: The 5-aminoimidazole-4-carboxamide ribonucleoside mediated improvements in glucose homeostasis in ob/ob mice can be explained by effects in skeletal muscle and liver. Due to the apparently deleterious effects of 5-aminoimidazole-4-carboxamide ribonucleoside on the blood lipid profile, strategies to develop tissue-specific and pathway-specific activators of 5'AMP-activated protein kinase should be considered in order to improve glucose homeostasis.
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| 12. |
- Ström Hallenberg, Gunilla, et al.
(författare)
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Antimicrobials in small-scale urban pig farming in a lower middle-income country - arbitrary use and high resistance levels
- 2018
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Ingår i: Antimicrobial Resistance and Infection Control. - : Springer Science and Business Media LLC. - 2047-2994. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 The Author(s). Background: Administration of antimicrobials to food-producing animals is regarded as a major contributor to the overall emergence of resistance in bacteria worldwide. However, few data are available on global antimicrobial use and resistance (AMR) in livestock, especially from low- and middle-income countries. Methods: We conducted a structured survey of 91 small-scale pig farms in the urban and peri-urban areas of Phnom Penh, Cambodia, to assess the farmers' knowledge, attitudes and practices related to antimicrobial use in their pig production. Commensal Escherichia coli was isolated from three healthy pigs from each farm (n = 261) and susceptibility testing was performed against 14 antimicrobials, using broth microdilution. Univariable logistic regression and generalized linear mixed models were used to investigate potential associations between farm characteristics, management factors and resistance to different types of antimicrobials. Results: We found a widespread and arbitrary use of antimicrobials, often based on the farmer's own judgment. Around 66% of the farmers reported frequently self-adjusting treatment duration and dosage, and 45% had not heard about the term 'antimicrobial resistance'. The antimicrobials most commonly mentioned or kept by the farmers were amoxicillin, tylosin, gentamicin and colistin. Around 37% used a feed concentrate that contained antimicrobials, while antimicrobials for humans were used as a last-line treatment by 10% of the farmers. Commensal E. coli exhibited high prevalence of resistance to several antimicrobials considered to be of critical importance for human medicine, including ampicillin, ciprofloxacin and colistin, and multidrug-resistance was found in 79% of the samples. Higher prevalence of resistance was observed on farms that administered prophylactic antimicrobials and on farms that treated the entire group or herd in the event of disease. Conclusion: The widespread and arbitrary use of antimicrobials in pig farming in Cambodia is highly worrisome. Overall, farmers had a low awareness of the risks and consequences related to antimicrobial use and AMR. The results presented in this study confirm the hypothesis that non-rational use of antimicrobials results in higher prevalence of AMR and highlight the need for professional animal health systems that involve medically rational use of antimicrobials in emerging economies such as Cambodia.
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| 13. |
- Trumpff, Caroline, et al.
(författare)
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Stress and circulating cell-free mitochondrial DNA : A systematic review of human studies, physiological considerations, and technical recommendations
- 2021
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Ingår i: Mitochondrion. - : Elsevier BV. - 1567-7249. ; 59, s. 225-245
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Forskningsöversikt (refereegranskat)abstract
- Cell-free mitochondrial DNA (cf-mtDNA) is a marker of inflammatory disease and a predictor of mortality, but little is known about cf-mtDNA in relation to psychobiology. A systematic review of the literature reveals that blood cf-mtDNA varies in response to common real-world stressors including psychopathology, acute psychological stress, and exercise. Moreover, cf-mtDNA is inducible within minutes and exhibits high intra-individual day-to-day variation, highlighting the dynamic regulation of cf-mtDNA levels. We discuss current knowledge on the mechanisms of cf-mtDNA release, its forms of transport (“cell-free” does not mean “membrane-free”), potential physiological functions, putative cellular and neuroendocrine triggers, and factors that may contribute to cf-mtDNA removal from the circulation. A review of in vitro, pre-clinical, and clinical studies shows conflicting results around the dogma that physiological forms of cf-mtDNA are pro-inflammatory, opening the possibility of other physiological functions, including the cell-to-cell transfer of whole mitochondria. Finally, to enhance the reproducibility and biological interpretation of human cf-mtDNA research, we propose guidelines for blood collection, cf-mtDNA isolation, quantification, and reporting standards, which can promote concerted advances by the community. Defining the mechanistic basis for cf-mtDNA signaling is an opportunity to elucidate the role of mitochondria in brain-body interactions and psychopathology.
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| 14. |
- Vuong, Mai T, et al.
(författare)
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Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy
- 2010
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Ingår i: KIDNEY INTERNATIONAL. - : Nature Publishing Group. - 0085-2538 .- 1523-1755. ; 78:12, s. 1281-1287
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Tidskriftsartikel (refereegranskat)abstract
- The Fc-alpha receptor (Fc alpha R/CD89) is involved in IgA complex formation and may affect the development of IgA nephropathy (IgAN). In this study, we tested the genetic variations of the CD89 gene in relation to disease susceptibility in IgAN and the expression of soluble CD89 (sCD89) in sera of patients with IgAN and in controls. There was a significant difference between the levels of sCD89-IgA complexes, measured by sandwich enzyme-linked immunosorbent assay (ELISA), in 177 patients with IgAN with and without disease progression at the time of first diagnosis. No such difference was found in 42 patients with other renal diseases. The patients with IgAN without disease progression had stable but high levels of sCD89 over 5-15 years of follow-up in contrast to stable but low levels of sCD89 in the disease progression group. Moreover, levels of sCD89 complexes were correlated with one of the five CD89 genetic variants in 212 patients with IgAN and 477 healthy Caucasians; the single-nucleotide polymorphism (SNP) rs11084377 was significantly associated with a lower expression of sCD89. However, no association between CD89 gene polymorphisms and susceptibility to IgAN was detected. Thus, we found an association between the levels of sCD89-IgA complexes in serum and the severity of IgAN, and a possible genetic component in regulating the production or expression of sCD89.
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| 15. |
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| 16. |
- Yngman-Uhlin, Pia, et al.
(författare)
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PD-patients expression of tiredness.
- 2009
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Ingår i: 42nd Annual Meeting, American Society of Nephrology (ASN).
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Konferensbidrag (refereegranskat)
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