| 1751. |
- Leifsdottir, Kristin, et al.
(författare)
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The cerebrospinal fluid proteome of preterm infants predicts neurodevelopmental outcome
- 2022
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Ingår i: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSurvival rate increases for preterm infants, but long-term neurodevelopmental outcome predictors are lacking. Our primary aim was to determine whether a specific proteomic profile in cerebrospinal fluid (CSF) of preterm infants differs from that of term infants and to identify novel biomarkers of neurodevelopmental outcome in preterm infants. MethodsTwenty-seven preterm infants with median gestational age 27 w + 4 d and ten full-term infants were enrolled prospectively. Protein profiling of CSF were performed utilizing an antibody suspension bead array. The relative levels of 178 unique brain derived proteins and inflammatory mediators, selected from the Human Protein Atlas, were measured. ResultsThe CSF protein profile of preterm infants differed from that of term infants. Increased levels of brain specific proteins that are associated with neurodevelopment and neuroinflammatory pathways made up a distinct protein profile in the preterm infants. The most significant differences were seen in proteins involved in neurodevelopmental regulation and synaptic plasticity, as well as components of the innate immune system. Several proteins correlated with favorable outcome in preterm infants at 18-24 months corrected age. Among the proteins that provided strong predictors of outcome were vascular endothelial growth factor C, Neurocan core protein and seizure protein 6, all highly important in normal brain development. ConclusionOur data suggest a vulnerability of the preterm brain to postnatal events and that alterations in protein levels may contribute to unfavorable neurodevelopmental outcome.
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| 1752. |
- Lemne, Carola, et al.
(författare)
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Dyslipoproteinemic changes in borderline hypertension
- 1994
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Ingår i: Hypertension. - 1524-4563. ; 24:5, s. 605-610
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Tidskriftsartikel (refereegranskat)abstract
- The present study examined plasma lipoprotein, lipoprotein lipase, hepatic lipase, and insulin levels in men with borderline hypertension (diastolic blood pressure 85 to 94 mm Hg) compared with age-matched normotensive control subjects (diastolic blood pressure less than or equal to 80 mm Hg, n = 75 + 75). High-density lipoprotein (HDL) subclasses were determined in a subset (n = 45 + 45). While total and low-density lipoprotein cholesterol levels were similar, levels of very-low-density lipoprotein (VLDL) cholesterol and triglycerides (0.46 versus 0.41 mmol/L, P = .027, and 1.0 versus 0.85 mmol/L, P = .031) and total triglycerides (1.53 versus 1.33 mmol/L, P = .009) were elevated and HDL cholesterol was reduced in the borderline group compared with the normotensive group (1.17 versus 1.26 mmol/L, P = .043). The HDL subclass HDL2b concentration was lower (0.16 versus 0.24 mmol/L, P = .006), while HDL3b and HDL3c concentrations were higher in the borderline group (0.38 versus 0.32 mmol/L, P = .016, and 0.19 versus 0.16 mmol/L, P = .042). Significantly higher activities of hepatic lipase in the borderline group (282 versus 232 mU/mL, P = .024) and significant correlations between lipoprotein lipase activity and VLDL and HDL concentrations suggest an involvement of these enzymes in the development of these differences. When adjusted for body mass index or insulin level, all differences disappeared, except for HDL3b and HDL3c concentrations, which remained significantly elevated. These results indicate that dyslipoproteinemic changes are present in early hypertension. Although most of these changes are related to obesity, alterations in HDL profile were not explained by influences of body mass index and insulin.
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| 1753. |
- Leosdottir, Margrét, et al.
(författare)
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Age and gender differences in the association between Nt-proBNP and glucometabolic disturbances.
- 2011
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Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 45, s. 294-300
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objectives. Glucometabolic disturbances are associated with myocardial dysfunction. Brain natriuretic peptides (BNP) are used for detecting myocardial dysfunction in clinical practice. However, studies on elderly subjects and gender-specific analyses are sparse. Design. We examined cross-sectional associations between Nt-proBNP and 1) fasting plasma glucose (FPG), and 2) categories of glucometabolic disturbances, in middle-aged and older subjects (1266 men, 526 women), applying multivariate linear regression analysis. Results. FPG was positively correlated with Nt-proBNP among middle-aged men (p = 0.04) and negatively albeit non-significantly (p = 0.1) among middle-aged women. Weaker non-significant correlations were seen among older subjects. Middle-aged men with new-onset and prevalent diabetes had higher Nt-proBNP than the reference group (FPG ≤5.0 mmol/L): 9.53 (p = 0.002) and 8.23 (p = 0.02) vs. 5.71 pmol/L. No differences in Nt-proBNP between categories of glucometabolic disturbance were observed among older men or women. Conclusions. The results indicate an age- and gender difference in the ability of Nt-proBNP to identify myocardial dysfunction in relation to glucometabolic disturbances. Therefore, Nt-proBNP should be used with caution as a general surrogate marker for myocardial dysfunction in this setting.
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| 1754. |
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| 1755. |
- Leosdottir, Margret, et al.
(författare)
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Myocardial structure and function by echocardiography in relation to glucometabolic status in elderly subjects from 2 population-based cohorts : a cross-sectional study
- 2010
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Ingår i: American Heart Journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 159:3, s. 4-420
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Left ventricular (LV) diastolic dysfunction has been associated with impaired glucometabolic status. However, studies of older subjects are lacking. We examined associations between echocardiographic indices of LV diastolic function and LV mass index (LVMI) and glucometabolic status among middle-aged and elderly subjects free from heart disease, hypothesizing that the associations would be comparative to younger cohorts.METHODS: We examined the Age Gene/Environment Susceptibility Reykjavik Study (Iceland; n = 607, 76 +/- 6 years) and the Malmö Preventive Project Re-Examination Study (MPP-RES) cohorts (Sweden; n = 1,519, 67 +/- 6 years), evaluating associations with multivariable regression analysis.RESULTS: In the Age Gene/Environment Susceptibility Reykjavik Study, LVMI was positively correlated with glycosylated hemoglobin (HbA1c) (P = .001). Otherwise, echocardiographic variables were not associated with glucometabolic status. In the MPP-RES, LVMI increased with increasing glucometabolic disturbance among both older (70-80 years) and middle-aged (57-69 years) subjects. Among older subjects, HbA1c was positively correlated with 2 variables reflecting LV diastolic function: late transmitral peak flow velocity (A) (P = .001) and early transmitral peak flow velocity (E)/early diastolic peak tissue velocity (Em) (P = .046). In middle-aged MPP-RES subjects, increasing glucometabolic disturbance was correlated with increasing late diastolic peak tissue velocity (Am) (P = .002) and, after age adjustment, with increasing A (P = .001) and decreasing Em/Am (P = .009). With age adjustment, Am and A were positively correlated with fasting glucose and HbA1c.CONCLUSIONS: Contrary to our hypothesis, in 2 independent cohorts of older individuals, associations between glucometabolic status and LV diastolic function were generally weak. These contrast with previous reports, as well as with observations among middle-aged subjects in the present study. Changes in LV diastolic function may be more age-related than associated with glucose metabolism in older subjects.
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| 1756. |
- Leosdottir, Margrét, et al.
(författare)
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The association between glucometabolic disturbances, traditional cardiovascular risk factors and self-rated health by age and gender: A cross-sectional analysis within the Malmo Preventive Project
- 2011
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 10:118
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Tidskriftsartikel (refereegranskat)abstract
- Background: The increased risk of cardiovascular disease (CVD) in diabetic compared to non-diabetic subjects seems to decrease with age. Whether this age-related reduction applies to CVD risk factors, and whether it is limited to established diabetes mellitus (DM) or also applies to pre-diabetic conditions are not well known. Methods: Using a cross-sectional design we compared the strength of the correlation between glucometabolic disturbances (by grouping), CVD risk factor burden and self-rated health, in two age groups: middle-aged (57-69 years) and older (70-86 years) subjects, (63% men), participating in the Malmo Preventive Project Re-examination Study (n = 18,238). Simple (unadjusted) logistic regression analysis was applied to estimate between-group differences and trends. Interaction analysis was applied to estimate differences between age groups. Results: CVD risk factor burden and the proportion of subjects reporting poor self-rated health increased with increasing glucometabolic disturbance for men and women in both age groups (p-trend < 0.0001 for all). The slope of the trend curve with increasing CVD risk factor burden was significantly steeper for older women than for older men (p-interaction = 0.002). The slope of the trend curve for poor self-rated health was significantly steeper for middle-aged than for older men (p-interaction = 0.005), while no difference was observed between the age groups among women (p-interaction = 0.97). Conclusions: We found no reduction in risk factor accumulation with increasing glucometabolic disturbance between middle-aged and older subjects. Our results indicate life-long CVD risk factor clustering with increased glucometabolic disturbance, and suggest that previously observed age-related reduction in excess CVD risk for subjects with DM might be due to a survival bias. However, our observations indicate more pronounced risk factor clustering and worse self-rated health with increased glucometabolic disturbance in older women than in older men.
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| 1757. |
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| 1758. |
- Lepp, Håkan, 1977-
(författare)
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Experimental studies of proton translocation reactions in biological systems : Electrogenic events in heme-copper oxidases
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Terminal heme-copper oxidases (HCuOs) are transmembrane proteins that catalyze the final step in the respiratory chain - the reduction of O2 to H2O, coupled to energy conservation by generation of an electrochemical proton gradient. The most extensively investigated of the HCuOs are the aa3-type oxidases, to which cytochrome c oxidase (CytcO) belongs, which uses energy released in the O2-reduction for proton pumping. The bacterial nitric oxide reductases (NORs) have been identified as divergent members of the HCuO-superfamily and are involved in the denitrification pathway where they catalyze the reduction of NO to NO2. Although as exergonic as O2-reduction, this reaction is completely non-electrogenic. Among the traditional HCuOs, the cbb3-type oxidases are the closest relatives to the NORs and as such provide a link between the aa3 oxidases and the NORs. The cbb3 oxidases have been shown to pump protons with nearly the same efficiency as the aa3 oxidases, despite low sequence similarity.This thesis is focused on measurements of membrane potential generating reactions during catalysis in the CytcO and the cbb3 oxidase from Rhodobacter sphaeroides, and the NOR from Paracoccus denitrificans, using a time resolved electrometric technique. The pH dependence of the membrane potential generation in CytcO showed that only one proton is taken up and that no protons are pumped, at high pH. An additional kinetic phase was also detected at high pH that presumably originates to from charge-transfer within the K-pathway. Possible reasons for uncoupling, and the extent of charge-transfer, were studied using structural variants of CytcO. The measurements established that electrons and protons are taken up from the same side of the membrane in NOR. In addition, the directionality for proton uptake in cbb3 oxidase appeared to be dependent on the choice of substrate while proton pumping was indicated to occur only during O2-reduction.
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| 1759. |
- Lerouge, Frederic, et al.
(författare)
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In vivo targeting and multimodal imaging of cerebral amyloid-beta aggregates using hybrid GdF3 nanoparticles
- 2022
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Ingår i: Nanomedicine. - : FUTURE MEDICINE LTD. - 1743-5889 .- 1748-6963. ; 17:29, s. 2173-2187
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To propose a new multimodal imaging agent targeting amyloid-beta (A beta) plaques in Alzheimers disease. Materials & methods: A new generation of hybrid contrast agents, based on gadolinium fluoride nanoparticles grafted with a pentameric luminescent-conjugated polythiophene, was designed, extensively characterized and evaluated in animal models of Alzheimers disease through MRI, two-photon microscopy and synchrotron x-ray phase-contrast imaging. Results & conclusion: Two different grafting densities of luminescent-conjugated polythiophene were achieved while preserving colloidal stability and fluorescent properties, and without affecting biodistribution. In vivo brain uptake was dependent on the blood-brain barrier status. Nevertheless, multimodal imaging showed successful A beta targeting in both transgenic mice and A beta fibril-injected rats.
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| 1760. |
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