| 1. |
- Arlock, Per, et al.
(författare)
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Ion currents of cardiomyocytes in different regions of the Göttingen minipig heart
- 2017
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Ingår i: Journal of Pharmacological and Toxicological Methods. - : Elsevier BV. - 1056-8719 .- 1873-488X. ; 86, s. 12-18
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The Göttingen minipig is a promising model for pharmacological safety assessment and for translational research in cardiology. We have examined the main ion currents in cardiomyocytes of the minipig heart. Methods Cardiac cells were isolated from different cardiac regions (endo-, mid- and epicardial left ventricle and right ventricle) from Göttingen minipigs and examined using the whole cell patch clamp technique combined with pharmacological interventions. Results The inward rectifier (IK1), the delayed rectifier (IK), with the rapid and slow components, (IKr, IKs) and the L-type Ca2 + channel (ICa,L) were identified in the different regions of the heart, whereas the Ca2 +-independent transient outward current (Ito1) was observed in only a few cells. IK1 was similar in the cardiac regions with a slightly lower value in the epicardial cells. IKs was smaller in epi- and endo-cardial regions. Discussion The equivalents of the main human cardiac ion currents are present in the minipig cardiomyocytes with the exception of the Ca2 +-independent Ito1. The study provides further evidence that the minipig is a valid model for investigating cardiovascular pharmacology.
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| 2. |
- Bozovic, Gracijela, et al.
(författare)
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Circulation stabilizing therapy and pulmonary high-resolution computed tomography in a porcine brain-dead model.
- 2016
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 60:1, s. 93-102
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Tidskriftsartikel (refereegranskat)abstract
- Currently 80% of donor lungs are not accepted for transplantation, often due to fluid overload. Our aim was to investigate if forced fluid infusion may be replaced by a new pharmacological therapy to stabilize circulation after brain death in an animal model, and to assess therapy effects on lung function and morphology trough blood gas parameters and state-of-the-art High-resolution CT (HRCT).
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| 3. |
- Darwiche, Gassan, et al.
(författare)
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An Okinawan-based Nordic diet improves anthropometry, metabolic control, and health-related quality of life in Scandinavian patients with type 2 diabetes : A pilot trial
- 2016
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Ingår i: Food and Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 60
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Tidskriftsartikel (refereegranskat)abstract
- Background: Our hypothesis was that a modified diet would improve blood glucose control with beneficial impact on weight management and overall health in established diabetes. Objective: This prospective interventional study investigated the clinical effect of an Okinawan-based Nordic diet on anthropometry, metabolic control, and health-related quality of life (HRQoL) in Scandinavian type 2 diabetes patients. Design: Food was prepared and delivered to 30 type 2 diabetes patients. Clinical information along with data on HRQoL, blood samples, and urine samples were collected during 12 weeks of diet interventions, with follow-up 16 weeks after diet completion. Results: After 12 weeks of dietary intervention, a reduction in body weight (7%) (p < 0.001), body mass index (p < 0.001), and waist circumference (7.0 cm) (p < 0.001) was seen. Improved levels of proinsulin (p = 0.005), insulin (p = 0.011), and fasting plasma glucose (p < 0.001) were found already after 2 weeks; these improved levels remained after 12 weeks when lowered levels of C-peptide (p = 0.015), triglycerides (p = 0.009), total cholesterol (p = 0.001), and low-density lipoprotein-cholesterol (p = 0.041) were also observed. Insulin resistance homeostasis model assessment for insulin resistance was lowered throughout the study, with a 20% reduction in hemoglobin A1c levels (p < 0.001) at week 12, despite reduced anti-diabetes treatment. Lowered systolic blood pressure (9.6 mmHg) (p < 0.001), diastolic blood pressure (2.7 mmHg) (p < 0.001), and heart and respiratory rates (p < 0.001) were accompanied by decreased cortisol levels (p = 0.015) and improvement in HRQoL. At follow-up, increased levels of high-density lipoprotein-cholesterol were found (p = 0.003). Conclusion: This interventional study demonstrates a considerable improvement of anthropometric and metabolic parameters and HRQoL in Scandinavian type 2 diabetes patients when introducing a modified Okinawan-based Nordic diet, independently of exercise or other interventions. Through these dietary changes, anti-diabetes treatment could be decreased or cancelled.
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| 4. |
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| 5. |
- Gjelstrup, Louise Carstensen, et al.
(författare)
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The role of higher-order protein structure in supporting binding by heteroclitic monoclonal antibodies: The monoclonal antibody KIM185 to CD18 also binds C4-binding protein
- 2011
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Ingår i: Molecular Immunology. - : Elsevier BV. - 1872-9142 .- 0161-5890. ; 49:1-2, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- Heteroclitic monoclonal antibodies are characterized by the ability to bind multiple epitopes with little or no similarity. Such antibodies have been reported earlier, but insight into to the molecular basis of this propensity is limited. Here we report that the KIM185 antibody to human CD18 reacts with the plasma protein C4b-binding protein (C4BP). This was revealed during affinity purification procedures where human serum was incubated with surfaces coated with monoclonal antibodies to CD18. Other monoclonal antibodies to CD18 (KIM127 and TS1/18) showed no such interaction with C4BP. We constructed a sandwich-type time-resolved immunofluorometric assay using KIM185 both as capture and developing antibody. By use of proteolytic fragments of KIM185 and recombinant deletion mutants of C4BP the interaction sites were mapped to the variable region of KIM185 and the oligomerization domain of C4BP, respectively. C4BP is a large oligomeric plasma protein that binds activated complement factor C4b and other endogenous ligands as well as microorganisms. By use of the recent crystallographic data on the structure of CD11c/CD18 and prediction of the secondary structure of the C4BP oligomerization domain, we show that epitopes bound by KIM185 in these proteins are unlikely to share any major structural similarity. However, both antigens may form oligomers that would enable avid binding by the antibody. Our report points to the astonishing ability of heteroclitic antibodies to accommodate the binding of multiple proteins with no or little structural similarity within the confined space of the variable regions. (C) 2011 Elsevier Ltd. All rights reserved.
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| 6. |
- Holmer, Helene, et al.
(författare)
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Improved general and oral health in diabetic patients by an okinawan-based nordic diet : A pilot study
- 2018
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 19:7
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Tidskriftsartikel (refereegranskat)abstract
- Periodontal disease, periodontitis as well as the preceding gingivitis, has been associated with both obesity and diabetes. Studies have shown that diet changes can lead to a lower incidence of such inflammation. The aim of the present case series over four weeks was to study the effects on medical and dental conditions in patients with type 2 diabetes of the consumption of the Okinawan-based Nordic Diet (OBND®). Medical and dental examinations were performed to estimate the general health and gingivitis/periodontitis. Serum cytokine levels were assessed using Luminex technology. Eight of ten study participants completed the study. All participants lost weight (p = 0.012). Six out of seven that were treated with insulin could reduce their insulin intake after two weeks with OBND®. The reduction was about 16 units which corresponds to a 34% relative reduction compared to the starting point (range 15–63%). Fasting blood glucose values fell (p = 0.035). Hemoglobin A1c (HbA1c) (p = 0.01), triglycerides (p = 0.05), and low-density lipoprotein (LDL) (p = 0.05) were also reduced. Bleeding on probing changed from ~28% before any dietary changes to ~13% after two weeks with OBND® (p = 0.01). The reduction in gingival bleeding was as substantial as might be expected from one session of professional tooth cleaning. Markers of inflammation were also reduced. The OBND® thus showed significant promise in alleviating the impact of diabetes on dental as well as general health.
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| 7. |
- Liao, Qiuming, et al.
(författare)
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Manual versus mechanical cardiopulmonary resuscitation. An experimental study in pigs
- 2010
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Optimal manual closed chest compressions are difficult to give. A mechanical compression/ decompression device, named LUCAS, is programmed to give compression according to the latest international guidelines (2005) for cardiopulmonary resuscitation (CPR). The aim of the present study was to compare manual CPR with LUCAS-CPR. Methods: 30 kg pigs were anesthetized and intubated. After a base-line period and five minutes of ventricular fibrillation, manual CPR (n = 8) or LUCAS-CPR (n = 8) was started and run for 20 minutes. Professional paramedics gave manual chest compression's alternating in 2-minute periods. Ventilation, one breath for each 10 compressions, was given to all animals. Defibrillation and, if needed, adrenaline were given to obtain a return of spontaneous circulation (ROSC). Results: The mean coronary perfusion pressure was significantly (p < 0.01) higher in the mechanical group, around 20 mmHg, compared to around 5 mmHg in the manual group. In the manual group 54 rib fractures occurred compared to 33 in the LUCAS group (p < 0.01). In the manual group one severe liver injury and one pressure pneumothorax were also seen. All 8 pigs in the mechanical group achieved ROSC, as compared with 3 pigs in the manual group. Conclusions: LUCAS-CPR gave significantly higher coronary perfusion pressure and significantly fewer rib fractures than manual CPR in this porcine model.
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| 8. |
- Lindstedt Ingemansson, Sandra, et al.
(författare)
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Comparative outcome of double lung transplantation using conventional donor lungs and non-acceptable donor lungs reconditioned ex vivo.
- 2010
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Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293.
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Tidskriftsartikel (refereegranskat)abstract
- A method to evaluate and recondition lungs ex vivo has been tested on donor lungs that have been rejected for transplantation. In the present paper, we compare early postoperative course between the six patients who received reconditioned lungs and the patients who received conventional donor lungs during the same period of time. During 2006 and 2007, a total of 21 patients underwent double sequential lung transplantation at the University Hospital of Lund. Six of those patients received reconditioned lungs. The other 15 patients received conventional donor lungs for transplantation without reconditioning ex vivo. The results are presented as median and interquartile range. Time in intensive care unit (days) between recipients of reconditioned lungs [13 (5-24) days], and recipients of conventional donor lungs [7 (5-12) days], P=0.44. Total hospital stay after transplantation (days) between recipients of reconditioned lungs [52 (47-60) days] and recipients of conventional donor lungs [44 (37-48) days], P=0.9. Ex vivo lung evaluation and reconditioning might not prolong early postoperative course in double lung transplantation. However, given the small number of patients, there might be a failure to detect a difference between the two groups. Keywords: Double lung transplantation; Reconditioned lungs; Clinical outcome.
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| 9. |
- Längin, Matthias, et al.
(författare)
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Consistent success in life-supporting porcine cardiac xenotransplantation
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 564:7736, s. 430-433
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Tidskriftsartikel (refereegranskat)abstract
- Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1–3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.
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| 10. |
- Metzsch, Carsten, et al.
(författare)
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Levosimendan cardioprotection in acutely beta-1 adrenergic receptor blocked open chest pigs.
- 2010
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 54, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Background: Levosimendan and volatile anesthetics have myocardial pre-conditioning effects. beta-1 adrenergic receptor antagonists may inhibit the protective effect of volatile anesthetics. No information exists as to whether this also applies to the pre-conditioning effect of levosimendan. We therefore investigated whether levosimendan added to metoprolol would demonstrate a cardioprotective effect. Methods: Three groups of anesthetized open chest pigs underwent 30 min of myocardial ischemia and 90 min of reperfusion by temporary occlusion of the largest side branch from the circumflex artery or the left anterior descending artery. One group (CTRL) served as a control, in another group (BETA), a metoprolol-loading dose was intravenously injected 30 min before ischemia, and in a third group (BETA+L), a levosimendan infusion was added to metoprolol. Myocardial tissue concentrations of glucose, glycerol, and lactate/pyruvate ratio as the primary end-points were investigated with microdialysis in ischemic and non-ischemic tissues. Results: At the end of the ischemic period, statistically significant differences were only found between CTRL and BETA+L in the ischemic myocardium, with a lower lactate/pyruvate ratio, lower glycerol, and higher glucose concentrations in BETA+L as compared with CTRL. There were no differences in non-ischemic myocardium. From 10 to 90 min of reperfusion, no more differences were found between groups. Conclusion: The cardioprotective effect of levosimendan on ischemic metabolism with a reduction in the myocardial lactate/pyruvate ratio, less glycerol accumulation, and better preserved glucose concentration does not seem to be prevented by beta-1 adrenergic receptor antagonism with metoprolol.
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