| 1. |
- Amundsen, Brage Høyem, et al.
(författare)
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A comparison of retrospectively self-gated magnetic resonance imaging and high-frequency echocardiography for characterization of left ventricular function in mice.
- 2011
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Ingår i: Laboratory animals. - : SAGE Publications. - 1758-1117 .- 0023-6772. ; 45:1, s. 31-37
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Tidskriftsartikel (refereegranskat)abstract
- Non-invasive imaging methods like echocardiography and magnetic resonance imaging (MRI) are very valuable in longitudinal follow-up studies of cardiac function in small animals. To be able to compare results from studies using different methods, and explain possible differences, it is important to know the agreement between these methods. As both self-gated high-field MRI and high-frequency echocardiography (hf-echo) M-mode are potential methods for evaluation of left ventricular (LV) function in healthy mice, our aim was to assess the agreement between these two methods. Fifteen healthy female C57BL/6J mice underwent both self-gated MRI and hf-echo during the same session of light isoflurane anaesthesia. LV dimensions were estimated offline, and agreement between the methods and reproducibility for the two methods assessed using Bland-Altman methods. In summary, hf-echo M-mode had better inter-observer repeatability than self-gated MRI for all measured parameters. Compared with hf-echo, systolic posterior wall thicknesses were significantly higher when measured by MRI, while diastolic anterior wall thicknesses were found to be significantly smaller. MRI measurements of diastolic LV diameter were also higher using MRI, resulting in larger fractional shortening values compared with the values obtained by hf-echo. In conclusion, hf-echo M-mode is easy to apply, has high temporal and spatial resolution, and good reproducibility. Self-gated MRI might be advantageous in cases of abnormal LV geometry and heterogeneous regional myocardial function, especially with improvements in spatial resolution. The moderate agreement between the methods must be taken into account when comparing studies using the two modalities.
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| 2. |
- Andersen, Sonja, et al.
(författare)
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Monoclonal B-cell hyperplasia and leukocyte imbalance precede development of B-cell malignancies in uracil-DNA glycosylase deficient mice
- 2005
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Ingår i: DNA Repair. - : Elsevier BV. - 1568-7864 .- 1568-7856. ; 4:12, s. 1432-1441
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Tidskriftsartikel (refereegranskat)abstract
- Ung-deficient mice have reduced class switch recombination, skewed somatic hypermutation, lymphatic hyperplasia and a 22-fold increased risk of developing B-cell lymphomas. We find that lymphomas are of follicular (FL) and diffuse large B-cell type (DLBCL). All FLs and 75% of the DLBCLs were monoclonal while 25% were biclonal. Monoclonality was also observed in hyperplasia, and could represent an early stage of lymphoma development. Lymphoid hyperplasia occurs very early in otherwise healthy Ung-deficient mice, observed as a significant increase of splenic B-cells. Furthermore, loss of Ung also causes a significant reduction of T-helper cells, and 50% of the young Ung(-/-) mice investigated have no detectable NK/NKT-cell population in their spleen. The immunological imbalance is confirmed in experiments with spleen cells where the production of the cytokines interferon gamma, interleukin 6 and interleukin 2 is clearly different in wild type and in Ung-deficient mice. This suggests that Ung-proteins, directly or indirectly, have important functions in the immune system, not only in the process of antibody maturation, but also for production and functions of immunologically important cell types. The immunological imbalances shown here in the Ung-deficient mice may be central in the development of lymphomas in a background of generalised lymphoid hyperplasia.
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| 3. |
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| 4. |
- Becirovic-Agic, Mediha, et al.
(författare)
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Time course of decompensation after angiotensin II and high-salt diet in Balb/CJ mice suggests pulmonary hypertension-induced cardiorenal syndrome
- 2019
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : the American Physiological Society. - 0363-6119 .- 1522-1490. ; 316:5, s. R563-R570
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of a mouse strain determines its susceptibility to disease. C57BL/6J and Balb/CJ are two widely used inbred mouse strains that we found react dramatically differently to angiotensin II and high-salt diet (ANG II + Salt). Balb/CJ show increased mortality associated with anuria and edema formation while C57BL/6J develop arterial hypertension but do not decompensate and die. Clinical symptoms of heart failure in Balb/CJ mice gave the hypothesis that ANG II + Salt impairs cardiac function and induces cardiac remodeling in male Balb/CJ but not in male C57BL/6J mice. To test this hypothesis, we measured cardiac function using echocardiography before treatment and every day for 7 days during treatment with ANG II + Salt. Interestingly, pulsed wave Doppler of pulmonary artery flow indicated increased pulmonary vascular resistance and right ventricle systolic pressure in Balb/CJ mice, already 24 h after ANG II + Salt treatment was started. In addition, Balb/CJ mice showed abnormal diastolic filling indicated by reduced early and late filling and increased isovolumic relaxation time. Furthermore, Balb/CJ exhibited lower cardiac output compared with C57BL/6J even though they retained more sodium and water, as assessed using metabolic cages. Left posterior wall thickness increased during ANG II + Salt treatment but did not differ between the strains. In conclusion, ANG II + Salt treatment causes early restriction of pulmonary flow and reduced left ventricular filling and cardiac output in Balb/CJ, which results in fluid retention and peripheral edema. This makes Balb/CJ a potential model to study the adaptive capacity of the heart for identifying new disease mechanisms and drug targets.
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| 5. |
- Berg, Kirsti, et al.
(författare)
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A High Precision Method for Quantitative Measurements of Reactive Oxygen Species in Frozen Biopsies
- 2014
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Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 9:3, s. e90964-
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Tidskriftsartikel (refereegranskat)abstract
- Objective: An electron paramagnetic resonance (EPR) technique using the spin probe cyclic hydroxylamine 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) was introduced as a versatile method for high precision quantification of reactive oxygen species, including the superoxide radical in frozen biological samples such as cell suspensions, blood or biopsies. Materials and Methods: Loss of measurement precision and accuracy due to variations in sample size and shape were minimized by assembling the sample in a well-defined volume. Measurement was carried out at low temperature (150 K) using a nitrogen flow Dewar. The signal intensity was measured from the EPR 1st derivative amplitude, and related to a sample, 3-carboxy-proxyl (CPN) with known spin concentration. Results: The absolute spin concentration could be quantified with a precision and accuracy better than +/- 10 mu M (k = 1). The spin concentration of samples stored at -80 degrees C could be reproduced after 6 months of storage well within the same error estimate. Conclusion: The absolute spin concentration in wet biological samples such as biopsies, water solutions and cell cultures could be quantified with higher precision and accuracy than normally achievable using common techniques such as flat cells, tissue cells and various capillary tubes. In addition; biological samples could be collected and stored for future incubation with spin probe, and also further stored up to at least six months before EPR analysis, without loss of signal intensity. This opens for the possibility to store and transport incubated biological samples with known accuracy of the spin concentration over time.
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| 6. |
- Berg, Kirsti, et al.
(författare)
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Acetylsalicylic acid treatment until surgery reduces oxidative stress and inflammation in patients undergoing coronary artery bypass grafting
- 2013
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 43:6, s. 1154-1163
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Acetylsalicylic acid (ASA) is a cornerstone in the treatment of coronary artery disease (CAD) due to its antiplatelet effect. Cessation of aspirin before coronary artery bypass grafting (CABG) is often recommended to avoid bleeding, but the practice is controversial because it is suggested to worsen the underlying CAD. The aims of the present prospective, randomized study were to assess if ASA administration until the day before CABG decreases the oxidative load through a reduction of inflammation and myocardial damage, compared with patients with preoperative discontinuation of ASA. METHODS: Twenty patients scheduled for CABG were randomly assigned to either routine ASA-treatment (160 mg daily) until the time of surgery (ASA), or to ASA-withdrawal 7 days before surgery (No-ASA). Blood-samples were taken from a radial artery and coronary sinus, during and after surgery and analysed for 8-iso-prostaglandin (PG) F(2α); a major F(2)-isoprostane, high-sensitivity C-reactive protein (hs-CRP), cytokines and troponin T. Left ventricle Tru-Cut biopsies were taken from viable myocardium close to the left anterior descending artery just after connection to cardiopulmonary bypass, and before cardioplegia were established for gene analysis (Illumina HT-12) and immunohistochemistry (CD45). RESULTS: 8-Iso-PGF(2α) at baseline (t(1)) were 111 (277) pmol/l and 221 (490) pmol/l for ASA and No-ASA, respectively (P = 0.065). Area under the curve showed a significantly lower level in plasma concentration of 8-iso-PGF(2α) and hsCRP in the ASA group compared with the No-ASA group with (158 pM vs 297 pM, P = 0.035) and hsCRP (8.4 mg/l vs 10.1 mg/l, P = 0.013). All cytokines increased during surgery, but no significant differences between the two groups were observed. Nine genes (10 transcripts) were found with a false discovery rate (FDR) <0.1 between the ASA and No-ASA groups. CONCLUSIONS: Continued ASA treatment until the time of CABG reduced oxidative and inflammatory responses. Also, a likely beneficial effect upon myocardial injury was noticed. Although none of the genes known to be involved in oxidative stress or inflammation took a different expression in myocardial tissue, the genetic analysis showed interesting differences in the mRNA level. Further research in this field is necessary to understand the role of the genes.
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| 7. |
- Burén, Jonas, et al.
(författare)
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A ketogenic low‐carbohydrate high‐fat diet increases ldl cholesterol in healthy, young, normal‐weight women : A randomized controlled feeding trial
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:3, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Ketogenic low‐carbohydrate high‐fat (LCHF) diets are popular among young, healthy, normal‐weight individuals for various reasons. We aimed to investigate the effect of a ketogenic LCHF diet on low‐density lipoprotein (LDL) cholesterol (primary outcome), LDL cholesterol sub-fractions and conventional cardiovascular risk factors in the blood of healthy, young, and nor-mal‐weight women. The study was a randomized, controlled, feeding trial with crossover design. Twenty‐four women were assigned to a 4 week ketogenic LCHF diet (4% carbohydrates; 77% fat; 19% protein) followed by a 4 week National Food Agency recommended control diet (44% carbo-hydrates; 33% fat; 19% protein), or the reverse sequence due to the crossover design. Treatment periods were separated by a 15 week washout period. Seventeen women completed the study and treatment effects were evaluated using mixed models. The LCHF diet increased LDL cholesterol in every woman with a treatment effect of 1.82 mM (p < 0.001). In addition, Apolipoprotein B‐100 (ApoB), small, dense LDL cholesterol as well as large, buoyant LDL cholesterol increased (p < 0.001, p < 0.01, and p < 0.001, respectively). The data suggest that feeding healthy, young, normal‐weight women a ketogenic LCHF diet induces a deleterious blood lipid profile. The elevated LDL cholesterol should be a cause for concern in young, healthy, normal‐weight women following this kind of LCHF diet.
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| 8. |
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| 9. |
- Caraballo, Remi, et al.
(författare)
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Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo
- 2015
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier. - 0223-5234 .- 1768-3254. ; 103, s. 191-209
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Tidskriftsartikel (refereegranskat)abstract
- The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Common. 2014, 450, 1063). Herein, we establish structure activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo. 2015 The Authors. Published by Elsevier Masson SAS.
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| 10. |
- Ericsson, Madelene, et al.
(författare)
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AMPK activator O304 improves metabolic and cardiac function, and exercise capacity in aged mice
- 2021
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Ingår i: Communications Biology. - : Nature Publishing Group. - 2399-3642. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Age is associated with progressively impaired, metabolic, cardiac and vascular function, as well as reduced work/exercise capacity, mobility, and hence quality of life. Exercise exhibit positive effects on age-related dysfunctions and diseases. However, for a variety of reasons many aged individuals are unable to engage in regular physical activity, making the development of pharmacological treatments that mimics the beneficial effects of exercise highly desirable. Here we show that the pan-AMPK activator O304, which is well tolerated in humans, prevented and reverted age-associated hyperinsulinemia and insulin resistance, and improved cardiac function and exercise capacity in aged mice. These results provide preclinical evidence that O304 mimics the beneficial effects of exercise. Thus, as an exercise mimetic in clinical development, AMPK activator O304 holds great potential to mitigate metabolic dysfunction, and to improve cardiac function and exercise capacity, and hence quality of life in aged individuals.
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