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Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Medicinska och farmaceutiska grundvetenskaper) > Högskolan Dalarna

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1.
  • Tour, Jeanette, et al. (författare)
  • Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls-antagonistic effects between opioid and serotonin-related genes.
  • 2017
  • Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 158:7, s. 1194-1203
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH.
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2.
  • Wan Saudi, Wan Salman, et al. (författare)
  • Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide
  • 2015
  • Ingår i: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 309:8, s. G625-G634
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuropeptide S (NPS) receptor (NPSR1) polymorphisms are associated with enteral dysmotility and inflammatory bowel disease (IBD). This study investigated the role of NPS in conjunction with nitrergic mechanisms in the regulation of intestinal motility and mucosal permeability. In rats, small intestinal myoelectric activity and luminal pressure changes in small intestine and colon, along with duodenal permeability were studied. In human intestine, NPS and NPSR1 were localized by immunostaining. Pre- and postprandial plasma NPS was measured by ELISA in healthy and active IBD humans. Effects and mechanisms of NPS were studied in human intestinal muscle strips. In rats, NPS 100-4000 pmol/kg·min had effects on the small intestine and colon. Low doses of NPS increased myoelectric spiking (p<0.05). Higher doses reduced spiking and prolonged the cycle length of the migrating myoelectric complex, reduced intraluminal pressures (p<0.05-0.01) and increased permeability (p<0.01) through NO-dependent mechanisms. In human intestine, NPS localized at myenteric nerve cell bodies and fibers. NPSR1 was confined to nerve cell bodies. Circulating NPS in humans was tenfold below the ~0.3 nmol/l dissociation constant (Kd) of NPSR1, with no difference between healthy and IBD subjects. In human intestinal muscle strips pre-contracted by bethanechol, NPS 1-1000 nmol/l induced NO-dependent muscle relaxation (p<0.05) that was sensitive also to tetrodotoxin (p<0.01). In conclusion, NPS inhibits motility and increases permeability in neurocrine fashion acting through NO in the myenteric plexus in rats and humans. Aberrant signaling and up-regulation of NPSR1 could potentially exacerbate dysmotility and hyperpermeability by local mechanisms in gastrointestinal functional and inflammatory reactions.
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4.
  • Grooten, W. J., et al. (författare)
  • Is active sitting as active as we think?
  • 2013
  • Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 56:8, s. 1304-14
  • Tidskriftsartikel (refereegranskat)
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5.
  • Thomas, Ilias, et al. (författare)
  • Sensor-based algorithmic dosing suggestions for oral administration of levodopa/carbidopa microtablets for Parkinson's disease : a first experience
  • 2019
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 266:3, s. 651-658
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Dosing schedules for oral levodopa in advanced stages of Parkinson's disease (PD) require careful tailoring to fit the needs of each patient. This study proposes a dosing algorithm for oral administration of levodopa and evaluates its integration into a sensor-based dosing system (SBDS).MATERIALS AND METHODS: In collaboration with two movement disorder experts a knowledge-driven, simulation based algorithm was designed and integrated into a SBDS. The SBDS uses data from wearable sensors to fit individual patient models, which are then used as input to the dosing algorithm. To access the feasibility of using the SBDS in clinical practice its performance was evaluated during a clinical experiment where dosing optimization of oral levodopa was explored. The supervising neurologist made dosing adjustments based on data from the Parkinson's KinetiGraph™ (PKG) that the patients wore for a week in a free living setting. The dosing suggestions of the SBDS were compared with the PKG-guided adjustments.RESULTS: The SBDS maintenance and morning dosing suggestions had a Pearson's correlation of 0.80 and 0.95 (with mean relative errors of 21% and 12.5%), to the PKG-guided dosing adjustments. Paired t test indicated no statistical differences between the algorithmic suggestions and the clinician's adjustments.CONCLUSION: This study shows that it is possible to use algorithmic sensor-based dosing adjustments to optimize treatment with oral medication for PD patients.
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6.
  • Sayols-Baixeras, Sergi, et al. (författare)
  • Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
  • 2023
  • Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 148:6, s. 459-472
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates.Methods: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of stool, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.Results: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.Conclusions: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
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8.
  • Arefalk, Gabriel, et al. (författare)
  • Smokeless tobacco (snus) and risk of heart failure : results from two Swedish cohorts
  • 2012
  • Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - : Sage Publications. - 1741-8267 .- 1741-8275 .- 2047-4873 .- 2047-4881. ; 19:5, s. 1120-1127
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure.Design: Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers. Methods: Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.Results: In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use.Conclusion: Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.
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9.
  • Bassil, A K, et al. (författare)
  • Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract.
  • 2007
  • Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 150:1, s. 58-64
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Obestatin, encoded by the ghrelin gene may inhibit gastrointestinal (GI) motility. This activity was re-investigated.EXPERIMENTAL APPROACH: Rat GI motility was studied in vitro (jejunum contractility and cholinergically-mediated contractions of forestomach evoked by electrical field stimulation; EFS) and in vivo (gastric emptying and intestinal myoelectrical activity). Ghrelin receptor function was studied using a GTPgammaS assay and transfected cells.KEY RESULTS: Contractions of the jejunum or forestomach were unaffected by obestatin 100 nM or 0.01-1000 nM, respectively (P>0.05 each; n=4-18). Obestatin (0.1-1 nM) reduced the ability of ghrelin 1 microM to facilitate EFS-evoked contractions of the stomach (increases were 42.7+/-7.8% and 21.2+/-5.0 % in the absence and presence of obestatin 1 nM; P<0.05; n=12); higher concentrations (10-1000 nM) tended to reduce the response to ghrelin but changes were not statistically significant. Similar concentrations of obestatin did not significantly reduce a facilitation of contractions caused by the 5-HT(4) receptor agonist prucalopride, although an inhibitory trend occurred at the higher concentrations (increases were 69.3+/-14.0% and 42.6+/-8.7% in the absence and presence of 1000 nM obestatin; n=10). Obestatin (up to 10 microM) did not modulate recombinant ghrelin receptor function. Ghrelin increased gastric emptying and reduced MMC cycle time; obestatin (1000 and 30,000 pmol kg(-1) min(-1)) had no effects. Obestatin (2500 pmol kg(-1) min(-1), starting 10 min before ghrelin) did not prevent the ability of ghrelin (500 pmol kg(-1) min(-1)) to shorten MMC cycle time.CONCLUSIONS AND IMPLICATIONS: Obestatin has little ability to modulate rat GI motility.
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10.
  • Nerpin, Elisabet, 1962-, et al. (författare)
  • Blood cell counts and C-reactive protein inrelation to lung function in NHANES 2007-2010
  • 2018
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Background:Low-grade systemic inflammation is associated with impaired lung function. Few studies have examined if C-reactive protein (CRP), blood eosinophil (B-Eos), and blood neutrophil (B-Neu) counts offer additive information in relation to lung function. The aim of this study was to analyse associations between CRP, BEos, and B-Neu and effects on lung function, with special regards to additive information.Methods:Cross-sectional study on 7,753 participants, 20-80 years of age, in the National Health and Nutrition Examination Survey. Gender-based tertiles for CRP, B-Eos, and B-Neu were analyzed in relation to forced expiratory volume in 1 second (FEV1 % predicted), forced vital capacity (FVC % predicted), and FEV1/FVC ratio.Results:CRP, B-Eos, and B-Neu were inversely related to FEV1 and FVC. Only B-Eos and B-Neu were inversely related to FEV1/FVC ratio. Further, lower lung function was found with increased number of elevatedinflammatory markers in the highest tertile (one, two or three vs. non elevated) for FEV1 (% predicted): β-coefficients (95% CI) -2.20(-2.98, -1.41), -4.43 (-5.39, -3.45), and -6.43(-8.07, -4.79), all P=0.001; FVC (% predicted): -1.70 (-2.42, -0.98), -3.17 (-4.06, -2.29), and -5.34 (-6.85, -3.84), all P=0.001.Conclusion:CRP, B-Eos, and B-Neu offer independent and additive information in relation to lower FEV1 and FVC in the general population. This indicates that a combination of biomarkers yields more information than the biomarkers assessed individually. The mechanisms appear to be different, as B-Neu and B-Eos seem to relate more closely to obstructive impairment, e.g., lower FEV1/FVC ratio, which was not found for CRP.
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