| 1. |
- Höglund, Odd, et al.
(författare)
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Blood pressure and heart rate during ovariohysterectomy in pyometra and control dogs: a preliminary investigation
- 2016
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Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Surgery causes a stress response, a physiologic response to trauma. The intraoperative surgical stress response in dogs diagnosed with pyometra has not previously been described. The aim of this study was to investigate the intraoperative surgical stress response, assessed by blood pressure and heart rate measurements, in dogs diagnosed with pyometra and healthy controls. All dogs were premedicated with acepromazine and methadone, anaesthesia was induced with propofol and maintained with isoflurane, where after the dogs were subjected to ovariohysterectomy.Results: Eight dogs diagnosed with pyometra and eight healthy controls were used. Systolic blood pressure and heart rate were measured to assess the surgical stress response. Additionally propofol dosage at induction of anaesthesia and the end-tidal isoflurane concentration were investigated. The surgery was split into four phases. Phase 0 was the period 10 min before the skin incision, phase 1 was skin incision and opening of abdomen, phase 2 was manipulation of uterine horns, lifting of the ovary with stretching of the mesovarium, ligation and transection of mesovarium and phase 3 was ligation and transection of cervix, removal of organs and closing of the abdomen. Dosage of propofol at induction of anaesthesia was 3.6 +/- 1 mg/kg in dogs with pyometra and 4.1 +/- 1 in healthy controls (P = 0.37). In both groups, systolic blood pressure increased between phase 1 and 2, from 87 +/- 15 to 114 19 mmHg in dogs with pyometra, and from 88 +/- 18 to 106 +/- 20 mmHg in healthy controls, (both P < 0.0001). Systolic blood pressure did not differ significantly between groups in any of the phases. Heart rate and end-tidal concentration of isoflurane did not differ significantly between phases or between groups.Conclusions: The increased blood pressure at removal of ovaries during ovariohysterectomy suggests a pronounced noxious stimulus at this part of the procedure. In principle, the study parameters and response to surgery did not differ significantly between dogs with pyometra and healthy controls.
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| 2. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 3. |
- Sandstedt, Joakim, et al.
(författare)
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COMP (Cartilage Oligomeric Matrix Protein) Neoepitope: A Novel Biomarker to Identify Symptomatic Carotid Stenosis
- 2021
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636 .- 1079-5642. ; 41:3, s. 1218-1228
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: COMP (cartilage oligomeric matrix protein) is abundantly expressed in the cardiovascular system, cartilage, and atherosclerotic plaques. We investigated if the total COMP (COMPtotal) and COMP neoepitope (COMPneo) with other cardiovascular markers and clinical parameters could identify symptomatic carotid stenosis. Approach and Results: Blood samples were collected from patients with symptomatic carotid stenosis (stenosis, n=50), patients with stroke without carotid stenosis but small plaques (plaque, n=50), and control subjects (n=50). COMPtotal and COMPneo were measured using an ELISA. Ninety-two cardiovascular disease markers were measured by the Olink CVD kit. The presence of native COMP and COMPneo was determined by immunohistochemistry. The concentration of COMPneo was higher and COMPtotal was lower in the stenosis group. When the concentration was compared between the stenosis and control groups, IL-1ra (interleukin-1 receptor antagonist protein), IL6 (interleukin-6), REN (Renin), MMP1 (matrix metalloproteinase-1), TRAIL-R2 (tumor necrosis factor-related apoptosis-inducing ligand receptor 2), ITGB1BP2 (integrin beta 1 binding protein 2), and COMPneo were predictive of stenosis. Conversely, KLK6 (kallikrein-6), COMPtotal, NEMO (nuclear factor-kappa-B essential modulator), SRC (Proto-oncogene tyrosine-protein kinase Src), SIRT2 (SIR2-like protein), CD40 (cluster of differentiation 40), TF (tissue factor), MP (myoglobin), and RAGE (receptor for advanced glycation end-products) were predictive of the control group. Model reproducibility was good with the receiver operating characteristic plot area under the curve being 0.86. When comparing the plaque group and stenosis group, COMPneo, GAL (galanin), and PTX3 (pentraxin-related protein PTX3) were predictive of stenosis. Model reproducibility was excellent (receiver operating characteristic plot area under the curve 0.92). COMPneo was detected in smooth muscle-, endothelial-, and foam-cells in carotid stenosis. CONCLUSIONS: Degradation of COMP may be associated with atherosclerosis progression and generation of a specific COMP fragment-COMPneo. This may represent a novel biomarker that together with COMPtotal and other risk-markers could be used to identify symptomatic carotid stenosis. Graphic Abstract: A graphic abstract is available for this article.
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| 4. |
- Arevström, Lilith, et al.
(författare)
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Freeze-dried bilberry (Vaccinium myrtillus) dietary supplement improves walking distance and lipids after myocardial infarction: an open-label randomized clinical trial
- 2019
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Ingår i: Nutrition Research. - : Elsevier BV. - 0271-5317 .- 1879-0739. ; 62, s. 13-22
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Tidskriftsartikel (refereegranskat)abstract
- Vaccinium myrtillus, have a high content of phenolic compounds including anthocyanins, which could provide cardiometabolic health benefits following acute myocardial infarction (AMI). We hypothesized that standard medical therapy supplemented with freeze-dried bilberry after AMI would have a more beneficial effect on cardiovascular risk markers and exercise capacity than medical therapy alone. Patients were allocated in a 1:1 ratio within 24 hours of percutaneous coronary intervention in an 8- week trial either to V myrtillus powder (40 g/d, equivalent to 480 g fresh bilberries) and standard medical therapy or to a control group receiving standard medical therapy alone. High-sensitivity C-reactive protein and exercise capacity measured with the 6-minute walk test were the primary biochemical and clinical end points, respectively. Fifty subjects completed the study. No statistically significant difference in high-sensitivity C-reactive protein was detected between groups. The mean 6-minute walk test distance increased significantly more in the bilberry group compared to the control group: mean difference 38 m at follow-up (95% confidence interval 14- 62, P =.003). Ex vivo oxidized low-density lipoprotein was significantly lowered in the bilberry group compared to control, geometric mean ratio 0.80 (95% confidence interval 0.66-0.96, P =.017), whereas total cholesterol and low-density lipoprotein cholesterol did not differ significantly between groups. Anthocyanin-derived metabolites in blood increased significantly in the bilberry group during the intervention and were different after 8 weeks between the bilberry group and control. Findings in the present study suggest that bilberries may have clinically relevant beneficial effects following AMI; a larger, double-blind clinical trial is warranted to confirm this.
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| 5. |
- Edvinsson, Marie, et al.
(författare)
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Iron Homeostasis in Tissues Is Affected during Persistent Chlamydia pneumoniae Infection in Mice
- 2017
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Ingår i: BioMed Research International. - : Hindawi Publishing Corporation. - 2314-6133 .- 2314-6141.
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia pneumoniae (C. pneumoniae) may be a mediator in the pathogenesis of atherosclerosis. For its growth C. pneumoniae depends on iron (Fe), but how Fe changes in tissues during persistent infection or affects bacterial replication in tissues is unknown. C. pneumoniae-infected C57BL/6J mice were sacrificed on days 4, 8, 20, and 40. Mice had bacteria in the lungs and liver on all days. Inflammatory markers, chemokine Cxcl2 and interferon-gamma, were not affected in the liver on day 40. The copper (Cu)/zinc (Zn) ratio in serum, another marker of infection/inflammation, increased on day 4 and tended to increase again on day 40. The Fe markers, transferrin receptor (TfR), Hepcidin (Hamp1), and ferroportin 1 (Fpn1), increased in the liver on day 4 and then normalized except for TfR that tended to decrease. TfR responses were similar to Fe in serum that increased on day 4 but tended to decrease thereafter. In the liver, Fe was increased on day 4 and also on day 40. The reappearing increases in Cu/Zn on day 40 concomitant with the increase in liver Fe on day 40, even though TfR tended to decrease, and the fact that viable C. pneumoniae was present in the lungs and liver may indicate the early phase of activation of recurrent infection.
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| 6. |
- Essner, Ann, et al.
(författare)
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Comparison of Polar® RS800CX heart rate monitor and electrocardiogram for measuring inter-beat intervals in healthy dogs
- 2015
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Ingår i: Physiology and Behavior. - : Elsevier. - 0031-9384 .- 1873-507X. ; 138:January, s. 247-253
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to assess the criterion validity, relative reliability and level of agreement ofPolar® RS800CX heart rate monitor measuring inter-beat intervals (IBIs), compared to simultaneously recordedelectrocardiogram (ECG) in dogs.Methods: Five continuous minutes of simultaneously recorded IBIs from Polar® RS800CX and Cardiostore ECG in11 adult healthy dogs maintaining standing position were analyzed. Polar® data was statistically compared toECG data to assess for systematic differences between the methods. Three different methods for handling missingIBI data were used. Criterion validities were calculated by intraclass correlation coefficients (ICCs) and corresponding95% confidence intervals (CIs). Relative reliabilities and levels of agreement were calculated by ICCsand the Bland and Altman analysis for repeated measurements per subject.Results: Correlation coefficients between IBI data from ECG and Polar® RS800CX varied between 0.73 and 0.84depending on how missing values were handled. Polar® was over- and underestimating IBI data compared toECG. The mean difference in log transformed (base10) IBI data was 0.8%, and 93.2% of the values were withinthe limits of agreement. Internally excluding three subjects presenting IBI series containing more than 5% erroneousIBIs resulted in ICCs between 0.97 and 0.99. Bland and Altman analysis (n = 8) showed mean differencewas 1.8 ms, and 98.5% of the IBI values were plotted inside limits of agreement.Conclusion: This study showed that Polar® systematically biased recorded IBI series and that it was fundamentalto detect measurement errors. For Polar® RS800CX heart rate monitor to be used interchangeably to ECG, byshowing excellent criterion validity and reliable IBI measures in group and individual samples, only less than5% of artifacts could be accepted.
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| 7. |
- Donat-Vargas, C., et al.
(författare)
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Cardiovascular and cancer mortality in relation to dietary polychlorinated biphenyls and marine polyunsaturated fatty acids : a nutritional-toxicological aspect of fish consumption
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:2, s. 197-209
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Tidskriftsartikel (refereegranskat)abstract
- Background: Co-exposure to environmental contaminants present in fish could mitigate the beneficial effects of fish consumption and possibly explain the lack of association observed for mortality in some geographical regions.Objective: To assess the independent associations of dietary exposure to polychlorinated biphenyls (PCBs) and long-chain omega-3 fish fatty acids intake with cardiovascular and cancer mortality.Methods: We used the prospective population-based Swedish Mammography Cohort and the Cohort of Swedish Men comprising 32 952 women and 36 545 men, free from cancer, cardiovascular disease and diabetes at baseline in 1998. Validated estimates of dietary PCBs and long-chain omega-3 fish fatty acids [i.e. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] intake were obtained via a food frequency questionnaire at baseline. Information on death was ascertained through register linkage.Results: During a mean follow-up of 15.5 years, we ascertained 16 776 deaths. We observed for cardiovascular mortality, comparing extreme quintiles in multivariable models mutually adjusted for PCBs and EPA-DHA, dose-dependent associations for dietary PCB exposure, hazard ratio (HR) 1.31 (CI 95%: 1.08 to 1.57; P-trend 0.005) and for dietary EPA-DHA intake, HR 0.79 (CI 95%: 0.66 to 0.95; P-trend 0.041). For cancer mortality, no clear associations were discerned.Conclusion: The beneficial effect of fish consumption on the cardiovascular system seems compromised by co-exposure to PCBs - one likely explanation for the inconsistent associations observed between fish consumption and mortality.
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| 8. |
- Handlin, Linda, et al.
(författare)
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Influence of Common Birth Interventions on Maternal Blood Pressure Patterns During Breastfeeding 2 Days After Birth
- 2012
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Ingår i: Breastfeeding Medicine. - : Mary Ann Liebert. - 1556-8253 .- 1556-8342. ; 7:2, s. 93-99
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study investigated possible influences of medical interventions during labor on maternal blood pressure during a breastfeed 2 days postpartum.Subjects and Methods: Sixty-six primiparae with normal deliveries were consecutively recruited. Blood pressure was measured at –5, 10, 30, and 60 minutes during a morning breastfeed 2 days postpartum. Five treatment groups were formed based on the medical interventions received during labor: Non-medicated mothers (Control group, n=21); mothers receiving epidural analgesia (EDA) with oxytocin (OT) stimulation (EDAOT group, n=14); mothers receiving EDA without OT stimulation (EDAnon-OT group, n=7); mothers receiving OT stimulation only (OT intravenously [iv] group, n=9); and mothers receiving 10 IU of OT intramuscularly (im) only (OT im group, n=15).Results: Baseline diastolic, but not systolic, blood pressure differed between the groups as displayed by significantly lower diastolic blood pressure in the EDAnon-OT group compared with the Control group, the OT iv group, and the EDAOT group (p=0.045, p=0.041, and p=0.024, respectively). Both systolic and diastolic blood pressure fell significantly during the breastfeeding session in the Control group (p=0.001 and p=0.004, respectively), the OT im group (p=0.006 and p=0.001, respectively), and the EDAOT group (p=0.028 and p=0.002, respectively), and the fall in diastolic blood pressure tended to be significant in the OT iv group (p=0.050). The duration of skin-to-skin contact before breastfeeding correlated positively with the decrease in systolic blood pressure in the OT im group (Rs=0.540, p=0.046).Conclusion: Administration of EDA during labor lowers baseline diastolic blood pressure and abolishes the fall in blood pressure in response to a breastfeed 2 days after birth.
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| 9. |
- Shi, Lin, 1988, et al.
(författare)
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Plasma metabolites associated with type 2 diabetes in a Swedish population: a case-control study nested in a prospective cohort
- 2018
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 61:4, s. 849-861
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The aims of the present work were to identify plasma metabolites that predict future type 2 diabetes, to investigate the changes in identified metabolites among individuals who later did or did not develop type 2 diabetes over time, and to assess the extent to which inclusion of predictive metabolites could improve risk prediction. Methods We established a nested case-control study within the Swedish prospective population-based Vasterbotten Intervention Programme cohort. Using untargeted liquid chromatography-MS metabolomics, we analysed plasma samples from 503 case-control pairs at baseline (a median time of 7 years prior to diagnosis) and samples from a subset of 187 case-control pairs at 10 years of follow-up. Discriminative metabolites between cases and controls at baseline were optimally selected using a multivariate data analysis pipeline adapted for large-scale metabolomics. Conditional logistic regression was used to assess associations between discriminative metabolites and future type 2 diabetes, adjusting for several known risk factors. Reproducibility of identified metabolites was estimated by intra-class correlation over the 10 year period among the subset of healthy participants; their systematic changes over time in relation to diagnosis among those who developed type 2 diabetes were investigated using mixed models. Risk prediction performance of models made from different predictors was evaluated using area under the receiver operating characteristic curve, discrimination improvement index and net reclassification index. Results We identified 46 predictive plasma metabolites of type 2 diabetes. Among novel findings, phosphatidylcholines (PCs) containing odd-chain fatty acids (C19: 1 and C17:0) and 2-hydroxyethanesulfonate were associated with the likelihood of developing type 2 diabetes; we also confirmed previously identified predictive biomarkers. Identified metabolites strongly correlated with insulin resistance and/or beta cell dysfunction. Of 46 identified metabolites, 26 showed intermediate to high reproducibility among healthy individuals. Moreover, PCs with odd-chain fatty acids, branched-chain amino acids, 3-methyl-2-oxovaleric acid and glutamate changed over time along with disease progression among diabetes cases. Importantly, we found that a combination of five of the most robustly predictive metabolites significantly improved risk prediction if added to models with an a priori defined set of traditional risk factors, but only a marginal improvement was achieved when using models based on optimally selected traditional risk factors. Conclusions/interpretation Predictive metabolites may improve understanding of the pathophysiology of type 2 diabetes and reflect disease progression, but they provide limited incremental value in risk prediction beyond optimal use of traditional risk factors.
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| 10. |
- Velikyan, Irina, et al.
(författare)
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Synthesis and preclinical evaluation of Ga-68-labeled collagelin analogs for imaging and quantification of fibrosis
- 2014
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 41:9, s. 728-736
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Fibrosis affecting functionality of vital organs such as liver, lung, heart, and kidney, is involved in many chronic diseases. Positron emission tomography (PET) would not only provide precise localization and extent of the affected tissue but also allow the accurate quantification of the fibrotic process for the subsequent prognosis. Methods: A cyclic peptide c[CPGRVMHGLHLGDDEGPC] conjugated either to 2-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7-triazonan-1-yl)acetic acid (NOTA(tBu)2) or 4-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7-triazacyclononan-1-yl)-5-(tert-butoxy)-5-oxopentanoic acid (NODAGA(tBu)3) via polyethylene glycol link (PEG2) was synthesized and labeled with Ga-68. Non-specific organ distribution, blood clearance, and excretion were investigated ex vivo in healthy rats. The binding specificity of the radioligands was assessed in vitro using autoradiography on cryosections of dog fibrotic heart tissue. Results: The yield of NOTA-PEG(2)-c[CPGRVMHGLHLGDDEGPC] and NODAGA-PEG(2)-c[CPGRVMHGLHLGDDEGPC] was 56% and 41%, respectively. Non-decay-corrected radiochemical yield was 80 +/- 5% with radiochemical purity of 95 +/- 4%. Pharmacokinetic studies in healthy male Sprague-Dawley rats showed fast blood clearance and renal excretion. Lower uptake in liver, spleen, and kidney was found for [[Ga-68]Ga-NOTA](+1)-PEG(2)-c [CPGRVMHGLHLGDDEGPC] as compared to [[Ga-68]Ga-NODAGA](0)-PEG(2)-c[CPGRVMHGLHLGDDEGPC]. Histologic evaluation of the left ventricle (LV) myocardium from a dog with severe mitral regurgitation (MR), revealed mild to moderate perivascular and subendocardial, and mild diffuse interstitial fibrosis. The tracer binding to the cryosections of the tissue was specific with the equilibrium Kd of 2.3 +/- 0.8 mu M and 2.1 +/- 0.9 mu M, respectively for [Ga-68]Ga-NO2A-Col and [Ga-68]Ga-NODAGA-Col. Conclusions: Two novel peptide based agents for the imaging of fibrosis by PET were developed. Moderation of the biodistribution could be achieved by variation of the charge on the complex moiety of the agents. The combination of the fast clearance from non-target organs as well as organs of interest such as lung, heart, and liver and binding specificity to the target tissue suggests the potential of the analogs for the imaging of fibrosis.
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