Publications by authors named "G Hege Thoresen"

110 Publications

Experiences of quality of life in people with Multiple Sclerosis who are in a wheelchair.

Nurs Open 2021 May 30. Epub 2021 May 30.

Faculty of Health and Welfare, Østfold University College, Fredrikstad, Norway.

Aim: The study includes health-related quality of life for people in Norway with multiple sclerosis who live at home and are in a wheelchair (N = 6). The purpose is to show how they experience living with a chronic disease such as MS and how they perceive their own situation. How they value their own health and what leads to positive consequences is central to this study.

Design: The study has a qualitative design to show what health-related experiences they had while living with MS.

Method: The interviews were conducted in their home and later transcribed. An interview guide with open-ended questions was used. The transcribed material was analysed with a thematic analysis.

Results: Key themes were being free and independent, threat to the self and one's identity, and adaptation to MS. Free and independent in everyday life was essential for all the informants. Being dependent on others for basic needs was something they sought to avoid. Adapting to the new situation of changing roles was a challenge that required a lot of them.
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http://dx.doi.org/10.1002/nop2.956DOI Listing
May 2021

Novel methods for cold exposure of skeletal muscle in vivo and in vitro show temperature-dependent myokine production.

J Therm Biol 2021 May 15;98:102930. Epub 2021 Apr 15.

National Institute of Occupational Health, Oslo, Norway. Electronic address:

Proteins secreted from skeletal muscle serving a signalling role have been termed myokines. Many of the myokines are exercise factors, produced and released in response to muscle activity. Cold exposures affecting muscle may occur in recreational, occupational and therapeutic settings. Whether muscle temperature independently affects myokine profile, is still to be elucidated. We hypothesized that manipulating muscle temperature by means of external cooling would change myokine production and release. In the present study we have established new models for cold exposure of muscle in vivo and in vitro where rat hind limb or cultured human myotubes were cooled to 18 °C. After a recovery period, muscle tissue, cells and culture media were harvested for further analysis by qPCR and immunoassays. Expression of several myokine genes were significantly increased after cold exposure in both models: in rat muscle, mRNA levels of CCL2 (p = 0.04), VEGFA (p = 0.02), CXCL1 (p = 0.02) and RBM3 (p = 0.02) increased while mRNA levels of IL-6 (p = 0.03) were decreased; in human myotubes, mRNA levels of IL6 (p = 0.01), CXCL8 (p = 0.04), VEGFA (p = 0.03) and CXCL1 (p < 0.01) were significantly increased, as well as intracellular protein levels of IL-8 (CXCL8 gene product; p < 0.01). The corresponding effect on myokine secretion was not observed, on the contrary, IL-8 (p = 0.02) and VEGF (VEGFA gene product) p < 0.01) concentrations in culture media were reduced after cold exposure in vitro. In conclusion, cold exposure of muscle in vivo and in vitro had an effect on the production and release of several known exercise-related myokines. Myokine expression at the level of mRNA and protein was increased by cold exposure, whereas secretion tended to be decreased.
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http://dx.doi.org/10.1016/j.jtherbio.2021.102930DOI Listing
May 2021

Effect of differentiation, de novo innervation, and electrical pulse stimulation on mRNA and protein expression of Na+,K+-ATPase, FXYD1, and FXYD5 in cultured human skeletal muscle cells.

PLoS One 2021 26;16(2):e0247377. Epub 2021 Feb 26.

Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

Denervation reduces the abundance of Na+,K+-ATPase (NKA) in skeletal muscle, while reinnervation increases it. Primary human skeletal muscle cells, the most widely used model to study human skeletal muscle in vitro, are usually cultured as myoblasts or myotubes without neurons and typically do not contract spontaneously, which might affect their ability to express and regulate NKA. We determined how differentiation, de novo innervation, and electrical pulse stimulation affect expression of NKA (α and β) subunits and NKA regulators FXYD1 (phospholemman) and FXYD5 (dysadherin). Differentiation of myoblasts into myotubes under low serum conditions increased expression of myogenic markers CD56 (NCAM1), desmin, myosin heavy chains, dihydropyridine receptor subunit α1S, and SERCA2 as well as NKAα2 and FXYD1, while it decreased expression of FXYD5 mRNA. Myotubes, which were innervated de novo by motor neurons in co-culture with the embryonic rat spinal cord explants, started to contract spontaneously within 7-10 days. A short-term co-culture (10-11 days) promoted mRNA expression of myokines, such as IL-6, IL-7, IL-8, and IL-15, but did not affect mRNA expression of NKA, FXYDs, or myokines, such as musclin, cathepsin B, meteorin-like protein, or SPARC. A long-term co-culture (21 days) increased the protein abundance of NKAα1, NKAα2, FXYD1, and phospho-FXYD1Ser68 without attendant changes in mRNA levels. Suppression of neuromuscular transmission with α-bungarotoxin or tubocurarine for 24 h did not alter NKA or FXYD mRNA expression. Electrical pulse stimulation (48 h) of non-innervated myotubes promoted mRNA expression of NKAβ2, NKAβ3, FXYD1, and FXYD5. In conclusion, low serum concentration promotes NKAα2 and FXYD1 expression, while de novo innervation is not essential for upregulation of NKAα2 and FXYD1 mRNA in cultured myotubes. Finally, although innervation and EPS both stimulate contractions of myotubes, they exert distinct effects on the expression of NKA and FXYDs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247377PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909653PMC
February 2021

Drug Use and Cancer Risk: A Drug-Wide Association Study (DWAS) in Norway.

Cancer Epidemiol Biomarkers Prev 2021 Apr 3;30(4):682-689. Epub 2020 Nov 3.

Department of Research, Cancer Registry of Norway, Oslo, Norway.

Background: Population-based pharmaco-epidemiologic studies are used to assess postmarketing drug safety and discover beneficial effects of off-label drug use. We conducted a drug-wide association study (DWAS) to screen for associations between prescription drugs and cancer risk.

Methods: This registry-based, nested case-control study, 1:10 matched on age, sex, and date of diagnosis of cases, comprises approximately 2 million Norwegian residents, including their drug history from 2004 to 2014. We evaluated the association between prescribed drugs, categorized according to the anatomical therapeutic chemical (ATC) classification system, and the risk of the 15 most common cancer types, overall and by histology. We used stratified Cox regression, adjusted for other drug use, comorbidity, county, and parity, and explored dose-response trends.

Results: We found 145 associations among 1,230 drug-cancer combinations on the ATC2-level and 77 of 8,130 on the ATC4-level. Results for all drug-cancer combinations are presented in this article and an online tool (https://pharmacoepi.shinyapps.io/drugwas/). Some associations have been previously reported, that is, menopausal hormones and breast cancer risk, or are likely confounded, that is, chronic obstructive pulmonary diseases and lung cancer risk. Other associations were novel, that is, inverse association between proton pump inhibitors and melanoma risk, and carcinogenic association of propulsives and lung cancer risk.

Conclusions: This study confirmed previously reported associations and generated new hypotheses on possible carcinogenic or chemopreventive effects of prescription drugs. Results from this type of explorative approach need to be validated in tailored epidemiologic and preclinical studies.

Impact: DWAS studies are robust and important tools to define new drug-cancer hypotheses..
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1028DOI Listing
April 2021

Substrate oxidation in primary human skeletal muscle cells is influenced by donor age.

Cell Tissue Res 2020 Dec 8;382(3):599-608. Epub 2020 Sep 8.

Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Blindern, P.O. Box 1068, 0316, Oslo, Norway.

Primary human myotubes represent an alternative system to intact skeletal muscle for the study of human diseases related to changes in muscle energy metabolism. This work aimed to study if fatty acid and glucose metabolism in human myotubes in vitro were related to muscle of origin, donor gender, age, or body mass index (BMI). Myotubes from a total of 82 donors were established from three different skeletal muscles, i.e., musculus vastus lateralis, musculus obliquus internus abdominis, and musculi interspinales, and cellular energy metabolism was evaluated. Multiple linear regression analyses showed that donor age had a significant effect on glucose and oleic acid oxidation after correcting for gender, BMI, and muscle of origin. Donor BMI was the only significant contributor to cellular oleic acid uptake, whereas cellular glucose uptake did not rely on any of the variables examined. Despite the effect of age on substrate oxidation, cellular mRNA expression of pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) did not correlate with donor age. In conclusion, donor age significantly impacts substrate oxidation in cultured human myotubes, whereas donor BMI affects cellular oleic acid uptake.
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http://dx.doi.org/10.1007/s00441-020-03275-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683494PMC
December 2020