| 1. |
- Bouyoucef, S E, et al.
(författare)
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Poster Session 2 : Monday 4 May 2015, 08
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Ferreira, Mjv, et al.
(författare)
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Poster Session 3 : Tuesday 5 May 2015, 08
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Markhus, R., et al.
(författare)
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EEG in fitness to drive evaluations in people with epilepsy - Considerable variations across Europe
- 2020
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Ingår i: Seizure-European Journal of Epilepsy. - : Elsevier BV. - 1059-1311. ; 79, s. 56-60
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Epilepsy patients consider driving issues to be one of their most serious concerns. Ideally, decisions regarding fitness to drive should be based upon thorough evaluations by specialists in epilepsy care. In 2009, an EU directive was published aiming to harmonize evaluation practices within European countries, but, despite these recommendations, whether all epileptologists use the same criteria is unclear. We therefore conducted this study to investigate routine practices on how epileptologists at European epilepsy centers evaluate fitness to drive. Methods: A questionnaire was sent to 63 contact persons identified through the European Epi-Care and the Epilepsy network. The questionnaire addressed how fitness-to-drive evaluations were conducted, the involvement of different professionals, the use and interpretation of EEG, and opinions on existing regulations and guidelines. Results: The questionnaire was completed by 35 participants (56 % response rate). Results showed considerable variation regarding test routines and the emphasis placed on the occurrence and extent of epileptiform discharges revealed by EEG. 82 % of the responders agreed that there was a need for more research on how to better evaluate fitness-to-drive in people with epilepsy, and 89 % agreed that regulations on fitness to drive evaluations should be internationally coordinated. Conclusion: Our survey showed considerable variations among European epileptologists regarding use of EEG and how findings of EEG pathology should be assessed in fitness-to-drive evaluations. There is a clear need for more research on this issue and international guidelines on how such evaluations should be carried out would be of value.
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| 4. |
- Virta, J, et al.
(författare)
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Impact of metabolic substrate modification on myocardial efficiency in a rat model of obesity and diabetes
- 2022
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Ingår i: European Heart Journal, Supplement. - : Oxford University Press (OUP). - 1520-765X .- 0195-668X .- 1522-9645. ; 43:2, s. 3076-3076
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Konferensbidrag (refereegranskat)abstract
- BackgroundCongenic leptin receptor deficient rat generated by introgression of the Koletsky leptin receptor mutation into BioBreeding Diabetes Resistant rat (BBDR.lepr−/−) is a novel animal model combining obesity, systemic insulin resistance and diabetes. Systemic insulin resistance is associated with reduced myocardial glucose utilization, but its effect on myocardial external efficiency, i.e. the ability of the myocardium to convert energy into external stroke work, remains uncertain.PurposeTo characterize cardiac energy metabolism and function in BBDR.lepr−/− rats and to study the effect of dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin in this model.MethodsCardiac phenotype was evaluated in six-month-old male BBDR.lepr−/− rats (n=11) and age-matched male non-diabetic lean control littermates (BBDR.lepr+/− or BBDR.lepr+/+ rats, n=14). Of these, 7 BBDR.lepr−/− rats and 6 controls underwent cardiac ultrasound, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), and [11C]acetate PET in order to evaluate cardiac structure and function as well as glucose and oxidative metabolism. In the remaining rats, fatty acid metabolism was evaluated by [18F]fluorothia-6-heptadecanoic acid ([18F]FTHA) PET/CT. In the linagliptin intervention study, 25 BBDR.lepr−/− male rats were randomly divided into control group (n=11) that received regular chow diet and linagliptin group (n=14) that received linagliptin (10mg/kg/d) mixed in the chow diet for three months. After the intervention, the rats underwent cardiac ultrasound, [18F]FDG PET/CT, and [11C]acetate PET.ResultsCompared with controls, BBDR.lepr−/− rats showed increased left ventricle (LV) mass (∼40%, p>0.001) and higher systolic blood pressure (∼10%, p=0.02). However, fractional shortening and cardiac output were similar in both groups. Myocardial fractional uptake rate of glucose measured with [18F]FDG PET was significantly reduced (∼86%, p=0.004) (Fig. 1A, E), whereas myocardial fatty acid uptake measured by [18F]FTHA PET was not significantly increased (free fatty acid (FFA) corrected standardized uptake value (SUV) ∼21%, p=0.54) (Fig. 1B) in BBDR.lepr−/− compared to controls. Myocardial oxygen consumption assessed by [11C]acetate PET was similar in both groups (Fig. 1C, E), but LV work per gram of myocardium was reduced (∼28%, p=0.001) resulting in reduced myocardial external efficiency (∼21%, p=0.03) (Fig. 1D) in BBDR.lepr−/− compared to controls. Treatment with linagliptin significantly enhanced myocardial fractional uptake rate of glucose (∼166%, p=0.006) (Fig. 2A, C), but had no effect on efficiency of cardiac work (Fig. 2B).ConclusionsObese and diabetic BBDR.lepr−/− rats demonstrate LV hypertrophy and markedly reduced myocardial glucose utilization associated with impaired myocardial external efficiency despite normal LV systolic function. Enhancement of myocardial glucose uptake by linagliptin did not improve efficiency of cardiac work.Funding AcknowledgementType of funding sources: Public grant(s) – EU funding. Main funding source(s): IMI-SUMMIT
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| 5. |
- Heikela, H., et al.
(författare)
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Hydroxysteroid (17 beta) dehydrogenase 12 is essential for metabolic homeostasis in adult mice
- 2020
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Ingår i: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 319:3
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxysteroid 17 beta dehydrogenase 12 (HSD17B12) is suggested to be involved in the elongation of very long chain fatty acids. Previously. we have shown a pivotal role for the enzyme during mouse development. In the present study we generated a conditional Hsd17b12 knockout (HSD17B12cKO) mouse model by breeding mice homozygous for a floxed Hsd17b12 allele with mice expressing the tamoxifen-inducible Cre recombinase at the ROSA26 locus. Gene inactivation was induced by administering tamoxifen to adult mice. The gene inactivation led to a 20% loss of body weight within 6 days, associated with drastic reduction in both white (83% males, 75% females) and brown (65% males. 60% females) fat, likely due to markedly reduced food and water intake. Furthermore, the knockout mice showed sickness behavior and signs of liver toxicity. specifically microvesicular hepatic steatosis and increased serum alanine aminotransferase (4.6-fold in males, 7.7-fold in females). The hepatic changes were more pronounced in females than males. Proinflammatory cytokines, such as interleukin-6 (IL-6), IL-17, and granulocyte colony-stimulating factor, were increased in the HSD17B12cKO mice indicating an inflammatory response. Serum lipidomics study showed an increase in the amount of dihydroceramides, despite the dramatic overall loss of lipids. In line with the proposed role for HSD17B12 in fatty acid elongation, we observed accumulation of ceramides, dihydroceramides, hexosylceramides, and lactosylceramides with shorter than 18-carbon fatty acid side chains in the serum. The results indicate that HSD17B12 is essential for proper lipid homeostasis and HSD17B12 deficiency rapidly results in fatal systemic inflammation and lipolysis in adult mice.
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| 6. |
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| 8. |
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| 9. |
- Davydova, B., et al.
(författare)
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Coxsackievirus immunization delays onset of diabetes in non-obese diabetic mice
- 2003
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Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 69:4, s. 510-520
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Tidskriftsartikel (refereegranskat)abstract
- Enteroviruses may be involved in the pathogenesis of Type 1 diabetes through different mechanisms including triggering of autoimmunity. The effect of immunization with coxsackievirus B4-E2 on diabetes incidence was studied in the non-obese diabetic mice, an animal model for human autoimmune insulin-dependent diabetes mellitus. The immunization delayed the onset of diabetes in the mice, and the effect was mediated at least partially by virus immunization-activated splenocytes as demonstrated by adoptive transfer experiments. Immunization resulted in a strong humoral immune response against the immunizing virus, formalin-inactivated coxsackievirus B4-E2. Cell-mediated immune responseto virus antigen was characterised by interferon gamma and interleukin 10 secretion. The immunization also resulted in increased antibody levels against several beta-cell autoantigens. By using epitope mapping we were able to show that in addition to reactivity with the known epitopes of viral proteins and tyrosine phosphatase A-2 or heat shock protein 60, responses to some other regions of autoantigens were enhanced. In preproinsulin, the response was restricted against an antigenic region earlier identified as DR4-dependent epitope. This reactivity can not be explained by homologous amino acid sequences and it is possible that enterovirus immunization might change the autoantigen specific TH1/TH2 balance in non-obese diabetic mice. In conclusion, our results suggest that coxsackievirus immunization increased humoral immune response to beta cell autoantigens and this was associated with a less destructive pathology for spontaneous diabetes in non-obese diabetic mice. © 2003 Wiley-Liss, Inc.
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| 10. |
- Harkonen, T, et al.
(författare)
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Enterovirus infection may induce humoral immune response reacting with islet cell autoantigens in humans
- 2003
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Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 69:3, s. 426-440
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Tidskriftsartikel (refereegranskat)abstract
- Molecular mimicry is one of the mechanisms by which enterovirus infections have been postulated to have a role in the pathogenesis of type 1 diabetes. Immunogenic epitopes in enterovirus capsid protein VP1 and procapsid protein VP0 have sequence similarities with diabetes-associated epitopes in tyrosine phosphatase IA-2/IAR and heat shock protein 60. In the present study, documented enterovirus infection was shown to induce humoral responses, that in 7% and 1% of patients cross-reacted with the known diabetes-associated epitopes in tyrosine phosphatase IAR and heat shock protein 60, respectively. In contrast, none of the children vaccinated against poliomyelitis had antibodies to the diabetes-associated epitope of tyrosine phosphatases IA-2/IAR. The antibody response studied in serum samples from six patients with coxsackievirus A9 infection was mainly targeted to capsid protein VP1. Coxsackievirus A9 infection induced antibodies cross-reacted with one epitope in heat shock protein 60, but not with epitopes derived from other autoantigens. Most diabetic children had high levels of antibodies to both coxsackievirus and poliovirus derived VP1 peptides but the pattern of reactivity did not differ from that seen in healthy children. The reactivity of linear epitopes derived from autoantigens was low in general and associated with the presence of multiple autoantibodies in the patients. Some linear auto-epitopes derived from tyrosine phosphatase IA-2, glutamic acid decarboxylase 65, preproinsulin, and heat shock protein 60 were recognized by sera from diabetic patients, but not by sera from healthy children. In conclusion, enteroviruses may induce immune responses that react with islet cell autoantigens, which is a concern when a putative inactivated enterovirus vaccine is considered.
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