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Sökning: WFRF:(Flyvbjerg Henrik)

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  • Holmstrup, Palle, et al. (författare)
  • Comorbidity of periodontal disease : two sides of the same coin? An introduction for the clinician
  • 2017
  • Ingår i: Journal of Oral Microbiology. - : Taylor & Francis Open. - 2000-2297 .- 2000-2297. ; 9:1
  • Forskningsöversikt (refereegranskat)abstract
    • Increasing evidence has suggested an independent association between periodontitis and a range of comorbidities, for example cardiovascular disease, type 2 diabetes, rheumatoid arthritis, osteoporosis, Parkinson's disease, Alzheimer's disease, psoriasis, and respiratory infections. Shared inflammatory pathways are likely to contribute to this association, but distinct causal mechanisms remain to be defined. Some of these comorbid conditions may improve by periodontal treatment, and a bidirectional relationship may exist, where, for example, treatment of diabetes can improve periodontal status. The present article presents an overview of the evidence linking periodontitis with selected systemic diseases and calls for increased cooperation between dentists and medical doctors to provide optimal screening, treatment, and prevention of both periodontitis and its comorbidities.
  • Laustsen, Christoffer, et al. (författare)
  • Antioxidant treatment attenuates lactate production in diabetic nephropathy
  • 2017
  • Ingår i: American Journal of Physiology - Renal Physiology. - : AMER PHYSIOLOGICAL SOC. - 0363-6127 .- 1522-1466 .- 1931-857X. ; 312:1, s. F192-F199
  • Tidskriftsartikel (refereegranskat)abstract
    • The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-(13)C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying increased lactate dehydrogenase activity as a consequence of increased nicotinamide adenine dinucleotide substrate availability due to upregulation of the polyol pathway, i.e., pseudohypoxia. In this study, we investigated the role of oxidative stress in mediating these metabolic alterations using state-of-the-art hyperpolarized magnetic resonance (MR) imaging. Ten-week-old female Wistar rats were randomly divided into three groups: healthy controls, untreated diabetic (streptozotocin treatment to induce insulinopenic diabetes), and diabetic, receiving chronic antioxidant treatment with TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl) via the drinking water. Examinations were performed 2, 3, and 4 wk after the induction of diabetes by using a 3T Clinical MR system equipped with a dual tuned (13)C/(1)H-volume rat coil. The rats received intravenous hyperpolarized [1-(13)C]pyruvate and were imaged using a slice-selective (13)C-IDEAL spiral sequence. Untreated diabetic rats showed increased renal lactate production compared with that shown by the controls. However, chronic TEMPOL treatment significantly attenuated diabetes-induced lactate production. No significant effects of diabetes or TEMPOL were observed on [(13)C]alanine levels, indicating an intact glucose-alanine cycle, or [(13)C]bicarbonate, indicating normal flux through the Krebs cycle. In conclusion, this study demonstrates that diabetes-induced pseudohypoxia, as indicated by an increased lactate-to-pyruvate ratio, is significantly attenuated by antioxidant treatment. This demonstrates a pivotal role of oxidative stress in renal metabolic alterations occurring in early diabetes.
  • Laustsen, Christoffer, et al. (författare)
  • High Intrarenal Lactate Production Inhibits the Renal Pseudohypoxic Response to Acutely Induced Hypoxia in Diabetes
  • 2019
  • Ingår i: Tomography. - : GRAPHO PUBLICATIONS. - 2379-1381 .- 2379-139X. ; 5:2, s. 239-247
  • Tidskriftsartikel (refereegranskat)abstract
    • Intrarenal hypoxia develops within a few days after the onset of insulinopenic diabetes in an experimental animal model (ie, a model of type-1 diabetes). Although diabetes-induced hypoxia results in increased renal lactate formation, mitochondrial function is well maintained, a condition commonly referred to as pseudohypoxia. However, the metabolic effects of significantly elevated lactate levels remain unclear. We therefore investigated in diabetic animals the response to acute intrarenal hypoxia in the presence of high renal lactate formation to delineate mechanistic pathways and compare these findings to healthy control animals. Hyperpolarized C-13-MRI and blood oxygenation level-dependent 1H-MRI was used to investigate the renal metabolism of [1-C-13] pyruvate and oxygenation following acutely altered oxygen content in the breathing gas in a streptozotocin rat model of type-1 diabetes with and without insulin treatment and compared with healthy control rats. The lactate signal in the diabetic kidney was reduced by 12%-16% during hypoxia in diabetic rats irrespective of insulin supplementation. In contrast, healthy controls displayed the well-known Pasteur effect manifested as a 10% increased lactate signal following reduction of oxygen in the inspired air. Reduced expression of the monocarboxyl transporter-4 may account for altered response to hypoxia in diabetes with a high intrarenal pyruvate-to-lactate conversion. Reduced intrarenal lactate formation in response to hypoxia in diabetes shows the existence of a different metabolic phenotype, which is independent of insulin, as insulin supplementation was unable to affect the pyruvate-to-lactate conversion in the diabetic kidney.
  • Laustsen, Christoffer, et al. (författare)
  • Insufficient insulin administration to diabetic rats increases substrate utilization and maintains lactate production in the kidney.
  • 2014
  • Ingår i: Physiological Reports. - 2051-817X. ; 2:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Good glycemic control is crucial to prevent the onset and progression of late diabetic complications, but insulin treatment often fails to achieve normalization of glycemic control to the level seen in healthy controls. In fact, recent experimental studies indicate that insufficient treatment with insulin, resulting in poor glycemic control, has an additional effect on progression of late diabetic complications, than poor glycemic control on its own. We therefore compared renal metabolic alterations during conditions of poor glycemic control with and without suboptimal insulin administration, which did not restore glycemic control, to streptozotocin (STZ)-diabetic rats using noninvasive hyperpolarized (13)C-pyruvate magnetic resonance imaging (MRI) and blood oxygenation level-dependent (BOLD) (1)H-MRI to determine renal metabolic flux and oxygen availability, respectively. Suboptimal insulin administration increased pyruvate utilization and metabolic flux via both anaerobic and aerobic pathways in diabetic rats even though insulin did not affect kidney oxygen availability, HbA1c, or oxidative stress. These results imply direct effects of insulin in the regulation of cellular substrate utilization and metabolic fluxes during conditions of poor glycemic control. The study demonstrates that poor glycemic control in combination with suboptimal insulin administration accelerates metabolic alterations by increasing both anaerobic and aerobic metabolism resulting in increased utilization of energy substrates. The results demonstrate the importance of tight glycemic control in insulinopenic diabetes, and that insulin, when administered insufficiently, adds an additional burden on top of poor glycemic control.
  • McGinn, Steven, et al. (författare)
  • New technologies for DNA analysis - a review of the READNA Project
  • 2016
  • Ingår i: New Biotechnology. - : Elsevier. - 1871-6784 .- 1876-4347. ; 33:3, s. 311-330
  • Forskningsöversikt (refereegranskat)abstract
    • The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received funding from the European Commission for 4 1/2 years. The objectives of the project revolved around technological developments in nucleic acid analysis. The project partners have discovered, created and developed a huge body of insights into nucleic acid analysis, ranging from improvements and implementation of current technologies to the most promising sequencing technologies that constitute a 3rd and 4th generation of sequencing methods with nanopores and in situ sequencing, respectively.
  • Reisner, Walter, et al. (författare)
  • Directed self-organization of single DNA molecules in a nanoslit via embedded nanopit arrays
  • 2009
  • Ingår i: Proceedings of the National Academy of Sciences. - : National Acad Sciences. - 1091-6490. ; 106:1, s. 79-84
  • Tidskriftsartikel (refereegranskat)abstract
    • We show that arrays of nanopit structures etched in a nanoslit can control the positioning and conformation of single DNA molecules in nanofluidic devices. By adjusting the spacing, organization and placement of the nanopits it is possible to immobilize DNA at predetermined regions of a device without additional chemical modification and achieve a high degree of control over local DNA conformation. DNA can be extended between two nanopits and in closely spaced arrays will self-assemble into "connect-the-dots" conformations consisting of locally pinned segments joined by fluctuating linkers. These results have broad implications for nanotechnology fields that require methods for the nanoscale positioning and manipulation of DNA.
  • Reisner, Walter, et al. (författare)
  • Nanoconfinement-enhanced conformational response of single DNA molecules to changes in ionic environment
  • 2007
  • Ingår i: Physical Review Letters. - : American Physical Society. - 1079-7114. ; 99:5
  • Tidskriftsartikel (refereegranskat)abstract
    • We show that the ionic environment plays a critical role in determining the configurational properties of DNA confined in silica nanochannels. The extension of DNA in the nanochannels increases as the ionic strength is reduced, almost tripling over two decades in ionic strength for channels around 100x100 nm in dimension. Surprisingly, we find that the variation of the persistence length alone with ionic strength is not enough to explain our results. The effect is due mainly to increasing self-avoidance created by the reduced screening of electrostatic interactions at low ionic strength. To quantify the increase in self-avoidance, we introduce a new parameter into the de Gennes theory: an effective DNA width that gives the increase in the excluded volume due to electrostatic repulsion.
  • Reisner, Walter, et al. (författare)
  • Single-molecule denaturation mapping of DNA in nanofluidic channels
  • 2010
  • Ingår i: Proceedings of the National Academy of Sciences. - : National Acad Sciences. - 1091-6490. ; 107:30, s. 13294-13299
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we explore the potential power of denaturation mapping as a single-molecule technique. By partially denaturing YOYO (R)-1-labeled DNA in nanofluidic channels with a combination of formamide and local heating, we obtain a sequence-dependent "barcode" corresponding to a series of local dips and peaks in the intensity trace along the extended molecule. We demonstrate that this structure arises from the physics of local denaturation: statistical mechanical calculations of sequence-dependent melting probability can predict the barcode to be observed experimentally for a given sequence. Consequently, the technique is sensitive to sequence variation without requiring enzymatic labeling or a restriction step. This technique may serve as the basis for a new mapping technology ideally suited for investigating the long-range structure of entire genomes extracted from single cells.
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