| 1. |
- Asif, Sana, M.D, PhD student, et al.
(författare)
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Validation of an MPC polymer coating to attenuate surface- induced cross-talk between the complement and coagulation systems in whole blood in in vitro and in vivo models
- 2019
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Ingår i: Macromolecular Bioscience. - : Wiley-VCH Verlagsgesellschaft. - 1616-5187 .- 1616-5195. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- Artificial surfaces that come into contact with blood induce an immediate activation of the cascade systems of the blood, leading to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Heparin coating has been used to improve hemocompatibility, and another approach is 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings. Here, the aim is to evaluate the hemocompatibility of MPC polymer coating by studying the interactions with coagulation and complement systems using human blood in vitro model and pig in vivo model. The stability of the coatings is investigated in vitro and MPC polymer-coated catheters are tested in vivo by insertion into the external jugular vein of pigs to monitor the catheters' antithrombotic properties. There is no significant activation of platelets or of the coagulation and complement systems in the MPC polymer-coated one, which was superior in hemocompatibility to non-coated matrix surfaces. The protective effect of the MPC polymer coat does not decline after incubation in human plasma for up to 2 weeks. With MPC polymer-coated catheters, it is possible to easily draw blood from pig for 4 days in contrast to the case for non-coated catheters, in which substantial clotting is seen.
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| 2. |
- Asif, Sana, M.D, PhD student, et al.
(författare)
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Validation of an MPC polymer coating to reduce surface-induced cascade system activation in whole blood in in vitroand in vivo models
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- ABSTRACTBackground: Artificial surfaces that come into contact with blood (e.g., when used in various forms of biomedical device) induce an immediate activation of the cascade systems of the blood, the coagulation and complement systems. These reactions may lead to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Multiple strategies to dampen these reactions have been employed, with heparin conjugation to the material surface being the most successfulthus far. Another approach to improving hemocompatibility is to use 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings.Experimental: In the present study, we evaluated the effectiveness of MPC polymer coating and compared it to a commercially available heparin coating in various in vitromodels using fresh human blood with the aim to replace the costly heparin-coated equipment with the more economic MPC. We then investigated the stability of the various coatings in human plasma in vitrofor 2 weeks. Finally, we inserted MPC polymer-coated catheters into the external jugular vein of pigs and monitored the catheters’ antithrombotic properties for 4 days.Results: 1) There was no significant activation of platelets and of the coagulation and complement systems on the MPC polymer-coated or the commercially available heparin surface. 2) Both coats were superior in hemocompatibility to non-coated matrix surfaces. 3) The protective effect of the MPC polymer coat did not decline after incubation in plasma for up to 2 weeks. 4) With MPC polymer-coated catheters, it was possible to easily draw blood from experimental animals for 4 days, in contrast to the case for heparin-flushed commercially available non-coated catheters, in which substantial clotting was seen.
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| 3. |
- Espes, Daniel, 1985-, et al.
(författare)
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Pancreatic perfusion and its response to glucose as measured by simultaneous PET/MRI
- 2019
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Ingår i: Acta Diabetologica. - : Springer. - 0940-5429 .- 1432-5233. ; 56:10, s. 1113-1120
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Perfusion of the pancreas and the islets of Langerhans is sensitive to physiological stimuli and is dysregulated in metabolic disease. Pancreatic perfusion can be assessed by both positron emission tomography (PET) and magnetic resonance imaging (MRI), but the methods have not been directly compared or benchmarked against the gold-standard microsphere technique.METHODS: Pigs (n = 4) were examined by [15O]H2O PET and intravoxel incoherent motion (IVIM) MRI technique simultaneously using a hybrid PET/MRI scanner. The pancreatic perfusion was measured both at basal conditions and after intravenous (IV) administration of up to 0.5 g/kg glucose.RESULTS: Pancreatic perfusion increased by 35%, 157%, and 29% after IV 0.5 g/kg glucose compared to during basal conditions, as assessed by [15O]H2O PET, IVIM MRI, and microspheres, respectively. There was a correlation between pancreatic perfusion as assessed by [15O]H2O PET and IVIM MRI (r = 0.81, R2 = 0.65, p < 0.01). The absolute quantification of pancreatic perfusion (ml/min/g) by [15O]H2O PET was within a 15% error of margin of the microsphere technique.CONCLUSION: Pancreatic perfusion by [15O]H2O PET was in agreement with the microsphere technique assessment. The IVIM MRI method has the potential to replace [15O]H2O PET if the pancreatic perfusion is sufficiently large, but not when absolute quantitation is required.
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| 4. |
- Grubb, Tamara, et al.
(författare)
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Effects of pulse-delivered inhaled nitric oxide administration on pulmonary perfusion and arterial oxygenation in dorsally recumbent isoflurane-anesthetized horses
- 2014
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Ingår i: American Journal of Veterinary Research. - : American Veterinary Medical Association (AVMA). - 0002-9645. ; 75, s. 949-955
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Tidskriftsartikel (refereegranskat)abstract
- Objective-To image the spatial distribution of pulmonary blood flow by means of scintigraphy, evaluate ventilation-perfusion (V-A/Q) matching and pulmonary blood shunting (Qs/Qt) by means of the multiple inert gas elimination technique (MIGET), and measure arterial oxygenation and plasma endothelin-1 concentrations before, during, and after pulse-delivered inhaled nitric oxide (PiNO) administration to isoflurane-anesthetized horses in dorsal recumbency.Animals-3 healthy adult Standardbreds.Procedures-Nitric oxide was pulsed into the inspired gases in dorsally recumbent isoflurane-anesthetized horses. Assessment of V-A/Q matching, Qs/Qt, and PaO2 content was performed by use of the MIGET, and spatial distribution of pulmonary blood flow was measured by perfusion scintigraphy following IV injection of technetium Tc 99m-labeled macroaggregated human albumin before, during, and 30 minutes after cessation of PiNO administration.Results-During PiNO administration, significant redistribution of blood flow from the dependent regions to the nondependent regions of the lungs was found and was reflected by improvements in V-A/Q matching, decreases in Qs/Qt, and increases in PaO2 content, all of which reverted to baseline values at 30 minutes after PiNO administration.Conclusions and Clinical Relevance-Administration of PiNO in anesthetized dorsally recumbent horses resulted in redistribution of pulmonary blood flow from dependent atelectatic lung regions to nondependent aerated lung regions. Because hypoxemia is commonly the result of atelectasis in anesthetized dorsally recumbent horses, the addition of nitric oxide to inhaled gases could be used clinically to alleviate hypoxemia in horses during anesthesia.
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| 5. |
- Grubb, Tamara L, et al.
(författare)
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Physiologic responses and plasma endothelin-1 concentrations associated with abrupt cessation of nitric oxide inhalation in isoflurane-anesthetized horses
- 2008
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Ingår i: American Journal of Veterinary Research. - : American Veterinary Medical Association (AVMA). - 0002-9645 .- 1943-5681. ; 69:3, s. 423-430
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess physiologic responses and plasma endothelin (ET)-1 concentrations associated with abrupt cessation of nitric oxide (NO) inhalation in isoflurane-anesthetized horses. ANIMALS: 6 healthy adult Standardbreds. PROCEDURES: Horses were anesthetized with isoflurane in oxygen and placed in dorsal recumbency. Nitric oxide was pulsed into the respiratory tract for 2.5 hours, and then administration was abruptly discontinued. Just prior to commencement and at cessation of NO administration, and at intervals during a 30-minute period following cessation of NO inhalation, several variables including PaO(2), mean pulmonary artery pressure, venous admixture or pulmonary shunt fraction (Qs/Qt), and plasma ET-1 concentration were recorded or calculated. RESULTS: After cessation of NO inhalation, PaO(2) decreased slowly but significantly (172.7 +/- 29.8 mm Hg to 84.6 +/- 10.9 mm Hg) and Qs/Qt increased slowly but significantly (25 +/- 2% to 40 +/- 3%) over a 30-minute period. Mean pulmonary artery pressure increased slightly (14.0 +/- 1.3 mm Hg to 16.8 +/- 1 mm Hg) over the same time period. No change in serum ET-1 concentration was detected, and other variables did not change or underwent minor changes. CONCLUSIONS AND CLINICAL RELEVANCE: The improvement in arterial oxygenation during pulsed inhalation of NO to healthy isoflurane-anesthetized horses decreased only gradually during a 30-minute period following cessation of NO inhalation, and serum ET-1 concentration was not affected. Because a rapid rebound response did not develop, inhalation of NO might be clinically useful in the treatment of hypoxemia in healthy isoflurane-anesthetized horses.
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| 6. |
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| 7. |
- Kautto, Ethel, et al.
(författare)
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What happens to food choices when a gluten-free diet is required? : A prospective longitudinal population-based study among Swedish adolescent with coeliac disease and their peers
- 2014
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Ingår i: Journal of Nutritional Science. - : Cambridge University Press. - 2048-6790. ; 3:e2
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Tidskriftsartikel (refereegranskat)abstract
- A dietary survey was performed during a large screening study in Sweden among 13-year-old adolescents. The aim was to study how the intake of food groups was affected by a screening-detected diagnosis of celiac disease (CD) and its gluten-free (GF) treatment. Food intake, was reported using a food frequency questionnaires (FFQ) and intake reported by the adolescents who was screened to CD was compared with the intake of two same-aged referent groups: i) adolescents diagnosed to CD prior screening and ii) adolescents without CD.. The food intake groups were measured at baseline before the screening-detected cases were aware of their CD, and 12-18 months later.The result showed that the food intakes are affected by a screen detected CD and its dietary treatment. Many flour-based foods were reduced such as pizza, fish fingers, and pastries. The result also indicated that the bread intake was lower before the screened diagnosis compared to the other studied groups, but increased afterwards. Specially manufactured GF-products (e.g. pasta and bread) were frequently used in the screened CDgroup after changing to a GF-diet. Our results suggest that changing to a GF-diet reduces the intake of some popular foods, and the ingredients on the plate are altered, but this do not necessarily include a change of food groups. The availability of manufactured GF-replacement products makes it possible for adolescents to keep many of their old food habits when diagnosed with CD in Sweden.
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| 8. |
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| 9. |
- Manell, Elin, et al.
(författare)
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Insulin treatment of streptozotocin-induced diabetes re-establishes the patterns in carbohydrate, fat and amino acid metabolisms in growing pigs
- 2014
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Ingår i: Laboratory Animals. - : SAGE Publications. - 0023-6772 .- 1758-1117. ; 48, s. 261-269
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Tidskriftsartikel (refereegranskat)abstract
- The effects of streptozotocin (STZ) were studied in eight high-health herd-certified Yorkshire x Swedish Landrace pigs (32.5 +/- 2.6 kg initial body weight [BW]), and an insulin treatment protocol was developed to re-establish their metabolisms. A single intravenous dose of 150mg STZ/kg BW successfully induced hyperglycaemia and alterations in their fat and protein metabolisms. Within 13 h post-STZ treatment blood glucose concentration had fallen to a range of 1.3 to 4.7 mmol/L. Hypoglycaemia was promptly treated with 0.5 g glucose/kg BW intravenously. All the pigs became hyperglycaemic with blood glucose concentrations >23 mmol/L within 48 h post-STZ. Two days post-STZ serum C-peptide concentrations fell below 60 rho mol/L in all the pigs and remained below 96 rho mol/L for five weeks until the end of the study. The pigs were left untreated for one week after STZ injection. At the end of this week 13-fold and nine-fold increases in serum concentrations of triglycerides and non-esterified fatty acids, respectively, were observed. Also, at this time-point a three-fold increase in the concentration of branched-chain amino acids (BCAA) was observed, and alanine and taurine were decreased by approximately 70% and 40%, respectively. During the week when the pigs were untreated, a reduced weight gain was observed, but after the onset of insulin treatment the daily weight gain was at least as good as that of conventional high-health pigs. Then a subcutaneous treatment with short-acting insulin was initiated. The initial dose of 2/3 IU/kg BW daily, divided between two doses, was gradually increased to 1 IU/kg BW. Within three weeks, the insulin treatment restored the metabolic changes in carbohydrate, fat and protein metabolisms produced by the STZ. In conclusion, the results underscore the usefulness of this animal model in translational research as insulin treatment re-establishes the changes in carbohydrate, fat and amino acid metabolisms observed in STZ-diabetic pigs and resolves clinical signs of disease similar to those in humans.
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| 10. |
- Nalin, Lovisa, et al.
(författare)
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Positron emission tomography imaging of the glucagon-like peptide-1 receptor in healthy and streptozotocin-induced diabetic pigs
- 2014
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 41:9, s. 1800-1810
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe glucagon-like peptide-1 receptor (GLP-1R) has been proposed as a target for molecular imaging of beta cells. The feasibility of non-invasive imaging and quantification of GLP-1R in pancreas using the positron emission tomography (PET) tracer [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 in non-diabetic and streptozotocin (STZ)–induced diabetic pigs treated with insulin was investigated.MethodsNon-diabetic (n = 4) and STZ-induced diabetic pigs (n = 3) from the same litter were examined. Development of diabetes was confirmed by blood glucose values, clinical examinations and insulin staining of pancreatic sections post mortem. Tissue perfusion in the pancreas and kidneys was evaluated by [15O]water PET/computed tomography (CT) scans. The in vivo receptor specificity of [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 was assessed by administration of either tracer alone or by competition with 3–6.5 μg/kg of Exendin-4. Volume of distribution and occupancy in the pancreas were quantified with a single tissue compartment model.Results[15O]water PET/CT examinations showed reduced perfusion in the pancreas and kidneys in diabetic pigs. [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 uptake in the pancreas of both non-diabetic and diabetic pigs was almost completely abolished by co-injection of unlabeled Exendin-4 peptide. [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 uptake did not differ between non-diabetic and diabetic pigs. In all animals, administration of the tracer resulted in an immediate increase in the heart rate (HR).ConclusionPancreatic uptake of [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 was not reduced by destruction of beta cells in STZ-induced diabetic pigs.
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