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| 2. |
- Engberg, Anna E., et al.
(författare)
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Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma
- 2015
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 36, s. 55-65
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Tidskriftsartikel (refereegranskat)abstract
- Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-gamma, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard. (C) 2014 Elsevier Ltd. All rights reserved.
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| 3. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 4. |
- Giordanetto, Fabrizio, et al.
(författare)
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Design of Selective sPLA2-X Inhibitor (-)-2-{2-[Carbamoyl-6-(trifluoromethoxy)-1 H-indol-1-yl]pyridine-2-yl}propanoic Acid
- 2018
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Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society. - 1948-5875. ; 9:7, s. 600-605
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Tidskriftsartikel (refereegranskat)abstract
- A lead generation campaign identified indole-based sPLA2-X inhibitors with a promising selectivity profile against other sPLA2 isoforms. Further optimization of sPLA2 selectivity and metabolic stability resulted in the design of (-)-17, a novel, potent, and selective sPLA2-X inhibitor with an exquisite pharmacokinetic profile characterized by high absorption and low clearance, and low toxicological risk. Compound (-)-17 was tested in an ApoE-/- murine model of atherosclerosis to evaluate the effect of reversible, pharmacological sPLA2-X inhibition on atherosclerosis development. Despite being well tolerated and achieving adequate systemic exposure of mechanistic relevance, (-)-17 did not significantly affect circulating lipid and lipoprotein biomarkers and had no effect on coronary function or histological markers of atherosclerosis.
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| 5. |
- Kindblom, Jenny, 1971, et al.
(författare)
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BMI change during puberty and the risk of heart failure
- 2018
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820. ; 283:6, s. 558-567
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Tidskriftsartikel (refereegranskat)abstract
- Aim. Hospitalization for heart failure amongst younger men has increased. The reason for this is unknown but it coincides with the obesity epidemic. The aim of this study was to evaluate the association between childhood BMI (Body Mass Index) and BMI change during puberty for risk of adult heart failure in men. Methods. Using the BMI Epidemiology Study (BEST), a population-based study in Gothenburg, Sweden, we collected information on childhood BMI at age 8 years and BMI change during puberty (BMI at age 20 - BMI at 8) for men born 1945-1961, followed until December 2013 (n = 37 670). BMI was collected from paediatric growth charts and mandatory military conscription tests. Information on heart failure was retrieved from high-quality national registers (342 first hospitalizations for heart failure). Results. BMI change during puberty was independently of childhood BMI associated with risk of heart failure in a nonlinear J-shaped manner. Subjects in the upper quartile of BMI change during puberty (Q4) had more than twofold increased risk of heart failure compared with subjects in Q1 [HR (Hazard Ratio) = 2.29, 95% CI (Confidence Interval) 1.68-3.12]. Childhood BMI was not independently associated with risk of heart failure. Boys developing overweight during puberty (HR 3.14; 95% CI 2.25-4.38) but not boys with childhood overweight that normalized during puberty (HR 1.12, 95% CI 0.63-2.00) had increased risk of heart failure compared with boys without childhood or young adult overweight. Conclusion. BMI change during puberty is a novel risk factor for adult heart failure in men.
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| 6. |
- Nyberg, Jenny, 1976, et al.
(författare)
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Cardiovascular fitness in late adolescent males and later risk of serious non-affective mental disorders: a prospective, population-based study.
- 2018
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Ingår i: Psychological medicine. - 1469-8978. ; 48:3, s. 416-425
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular fitness in late adolescence is associated with future risk of depression. Relationships with other mental disorders need elucidation. This study investigated whether fitness in late adolescence is associated with future risk of serious non-affective mental disorders. Further, we examined how having an affected brother might impact the relationship.Prospective, population-based cohort study of 1 109 786 Swedish male conscripts with no history of mental illness, who underwent conscription examinations at age 18 between 1968 and 2005. Cardiovascular fitness was objectively measured at conscription using a bicycle ergometer test. During the follow-up (3-42 years), incident cases of serious non-affective mental disorders (schizophrenia and schizophrenia-like disorders, other psychotic disorders and neurotic, stress-related and somatoform disorders) were identified through the Swedish National Hospital Discharge Register. Cox proportional hazards models were used to assess the influence of cardiovascular fitness at conscription and risk of serious non-affective mental disorders later in life.Low fitness was associated with increased risk for schizophrenia and schizophrenia-like disorders [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.29-1.61], other psychotic disorders (HR 1.41, 95% CI 1.27-1.56), and neurotic or stress-related and somatoform disorders (HR 1.45, 95% CI 1.37-1.54). Relationships persisted in models that included illness in brothers.Lower fitness in late adolescent males is associated with increased risk of serious non-affective mental disorders in adulthood.
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| 7. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Association between excessive BMI increase during puberty and risk of cardiovascular mortality in adult men: a population-based cohort study.
- 2016
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595. ; 4:12, s. 1017-1024
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Tidskriftsartikel (refereegranskat)abstract
- Being overweight during childhood and adolescence is associated with increased risk of cardiovascular disease in adulthood, but the relative contribution of prepubertal childhood BMI and BMI change during puberty to adult mortality due to cardiovascular disease is unknown. We assessed the contribution of these two distinct developmental BMI parameters for cardiovascular mortality in adult men.As a part of the ongoing population-based BMI Epidemiology Study (BEST) in Gothenburg, Sweden, men born between 1945 and 1961 with information on both their childhood BMI at age 8 years and BMI change during puberty were included in the study and followed up until December, 2013. Participants who died or emigrated before age 20 years were excluded from the analysis. BMI was collected from paediatric growth charts and mandatory military conscription tests. Childhood overweight (BMI of ≥17·9 kg/m(2)) was defined according to the Centers for Disease Control and Prevention's cutoff at 8 years of age, and BMI change during puberty was defined as the difference between young adult BMI and childhood BMI (BMI at age 20 years minus BMI at age 8 years). Information on mortality was retrieved from high quality national registers with the participants' ten-digit personal identity number. We used Cox proportional hazard regression to analyse the association between exposures and mortality. The ethics committee of the University of Gothenburg, Sweden, approved the study and waived the requirement for written informed consent.We followed 37672 Swedish men from age 20 years for a mean of 37·8 years (1422185 person-years follow-up). 3188 all-cause deaths and 710 cardiovascular deaths occurred during follow-up. The correlation between childhood BMI and BMI change during puberty was marginal (r=0·06). BMI change during puberty, but not childhood BMI, was independently associated with adult all-cause and cardiovascular mortality in men. Boys that became overweight during puberty (HR 2·39; 95% CI 1·86-3·09) and boys who were overweight consistently throughout childhood and puberty (1·85; 1·28-2·67), but not boys overweight in childhood that normalised during puberty (0·99, 0·65-1·50), had increased risk of cardiovascular mortality compared with participants who were not overweight in childhood or as young adults. The association between BMI change during puberty and cardiovascular mortality was non-linear with a substantial association above a threshold of 6·7 units increase in BMI.Excessive BMI increase during puberty is a risk marker of adult cardiovascular mortality. These results indicate that BMI should be monitored during puberty to identify boys with increased risk of adult cardiovascular mortality.Swedish Research Council, the Swedish Government (under the Avtal om Läkarutbildning och Medicinsk Forskning [Agreement for Medical Education and Research]), the Lundberg Foundation, the Torsten Söderberg Foundation, the Novo Nordisk Foundation, the Knut and Alice Wallenberg Foundation, and the Anna Ahrenberg Foundation.
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| 8. |
- Ohlsson, Claes, 1965, et al.
(författare)
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BMI change during puberty is an important determinant of adult type 2 diabetes risk in men.
- 2019
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 104:5, s. 1823-1832
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine the role of change in body mass index (BMI) during puberty, independent of childhood overweight, for the risk of adult type 2 diabetes in men.We included 36,176 men who had weight and height measured at age 8 (childhood) and 20 (young adult age) available from the BMI Epidemiology Study (BEST) and the Conscription register. Information on type 2 diabetes (n=1,777) was retrieved from the Swedish National Patient Register. Hazard ratios and 95% Confidence Intervals were estimated by Cox regressions including birth year and country of birth as covariates. Because the assumption of proportional hazards was violated for the association between BMI change during puberty and type 2 diabetes, we split the follow-up time into early (≤55.7 years) and late (>55.7 years).Both childhood overweight and a high BMI increase during puberty associated with risk of adult type 2 diabetes. Men with childhood overweight that normalized during puberty did not have a significantly increased risk of type 2 diabetes (Early type 2 diabetes 1.28[0.89; 1.82]; Late type 2 diabetes 1.35[0.97; 1.87]). Men who developed overweight during puberty (Early 4.67[3.90; 5.58]; Late 2.85[2.25; 3.61]) and men overweight at both childhood and young adult age (Early 4.82[3.84; 6.05]; Late 3.04[2.27; 4.06]) had substantially increased risk of type 2 diabetes compared with men who were never overweight.BMI change during puberty is an important, and childhood BMI a modest, independent determinant of adult type 2 diabetes risk in men.
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| 9. |
- Ohlsson, Claes, 1965, et al.
(författare)
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BMI increase through puberty and adolescence is associated with risk of adult stroke
- 2017
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 89:4, s. 363-369
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the contribution of prepubertal childhood body mass index (BMI) and BMI change through puberty and adolescence, 2 distinct developmental BMI parameters, for risk of adult stroke in men. Methods: In this population-based study in Gothenburg, Sweden, men born in 1945-1961 with information on both childhood BMI at age 8 and BMI change through puberty and adolescence (BMI at age 20-BMI at age 8) were followed until December 2013 (n = 37,669). Information on stroke events was retrieved from high-quality national registers (918 first stroke events, 672 ischemic stroke events [IS], 207 intracerebral hemorrhage events [ICH]). Results: BMI increase through puberty and adolescence (hazard ratio [HR] 1.21 per SD increase; 95% confidence interval [CI] 1.14-1.28), but not childhood BMI, was independently associated with risk of adult stroke. Subanalyses revealed that BMI increase through puberty and adolescence was associated with both IS (HR per SD increase 1.19; 95% CI 1.11-1.28) and ICH (HR per SD increase 1.29; 95% CI 1.15-1.46). High BMI increase during puberty was strongly associated with increased risk of adult hypertension (odds ratio per SD increase 1.35; 95% CI 1.32-1.39). Conclusions: BMI increase through puberty and adolescence is associated with risk of adult IS and ICH in men. We propose that greater BMI increases during puberty contribute to increased risk of adult stroke at least partly via increased blood pressure.
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| 10. |
- Rosengren-Holmberg, Jenny P., et al.
(författare)
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Heparin molecularly imprinted surfaces for the attenuation of complement activation in blood
- 2015
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Ingår i: Biomaterials Science. - : Royal Society of Chemistry (RSC). - 2047-4830 .- 2047-4849. ; 3:8, s. 1208-1217
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Tidskriftsartikel (refereegranskat)abstract
- Heparin-imprinted synthetic polymer surfaces with the ability to attenuate activation of both the complement and the coagulation system in whole blood were successfully produced. Imprinting was achieved using a template coated with heparin, a highly sulfated glycosaminoglycan known for its anticoagulant properties. The N,N'-diacryloylpiperazine-methacrylic acid copolymers were characterized using goniometry, AFM and XPS. The influence of the molecular imprinting process on morphology and template rebinding was demonstrated by radioligand binding assays. Surface hemocompatibility was evaluated using human whole blood without anticoagulants followed by measurement of complement activation markers C3a and sC5b-9 and platelet consumption as a surrogate coagulation activation marker. The observed low thrombogenicity of this copolymer combined with the attenuation of complement activation induced by the molecular imprint offer potential for the development of self-regulating surfaces with important potential clinical applications. We propose a mechanism for the observed phenomena based upon the recruitment of endogenous sulfated glycosaminoglycans with heparin-like activities.
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