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| 2. |
- Hellström, P. M., et al.
(författare)
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GLP-1 suppresses gastrointestinal motility and inhibits the migrating motor complex in healthy subjects and patients with irritable bowel syndrome
- 2008
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 20:6, s. 649-659
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide-1 (GLP-1) is released after food intake to act as an incretin. GLP-1 also inhibits gastric emptying and increases satiety. In rats, GLP-1 inhibits small bowel motility. Our aim was to study the effects of GLP-1 on gastrointestinal motility in healthy subjects and patients with irritable bowel syndrome (IBS). Antro-duodeno-jejunal manometry was carried out during a 4-h control period with saline, followed by a 4-h period with intravenous GLP-1 (healthy: 0.7 and 1.2 pmol kg-1 min-1 (n = 16), IBS, 1.2 and 2.5 pmol kg-1 min-1 (n = 14). Plasma was analysed for GLP-1 and gut hormones, and gut tissue expression of GLP-1 receptor was studied. In healthy subjects, GLP-1 0.7 pmol kg-1 min-1 reduced the migrating motor complexes (MMCs) from a median of 2 (range 2-3) to 0.5 (0-2), and motility index from 4.9 ± 0.1 to 4.3 ± 0.3 ln ∑(mmHg*s min-1) in jejunum, while GLP-1 1.2 pmol kg -1 min-1 diminshed MMCs from 2 (2-3) to 1.5 (1-2.5), and motility index from 5.2 ± 0.2 to 4.4 ± 0.2. In IBS patients, GLP-1 1.2 pmol kg-1 min-1 reduced the MMCs from 2.5 (2-3.5) to 1 (0-1.5) without affecting motility index. At 2.5 pmol kg-1 min -1 GLP-1 decreased MMCs from 2 (1.5-3) to 1 (0.5-1.5), and motility index from 5.2 ± 0.2 to 4.0 ± 0.5. Motility responses to GLP-1 were similar in antrum and duodenum. Presence of the GLP-1 receptor in the gut was verified by reverse transcriptase PCR. In conclusion, the gut peptide GLP-1 decreases motility in the antro-duodeno-jejunal region and inhibits the MMC in healthy subjects and IBS patients. © 2008 The Authors.
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| 3. |
- Barack, Leor, et al.
(författare)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Forskningsöversikt (refereegranskat)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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| 4. |
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| 5. |
- Edholm, T., et al.
(författare)
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Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis
- 2010
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:11, s. 1191-e315
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Tidskriftsartikel (refereegranskat)abstract
- Background Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are major incretins with important effects on glucoregulatory functions. The aim of this study was to investigate effects of GIP and GLP-1 on gastric emptying and appetite after a mixed meal, and effects on insulin secretion and glucose disposal in humans. Methods Randomized crossover single-blind study in 17 healthy volunteers receiving GIP (2 or 5 pmol kg−1 min−1, n = 8), GLP-1 (0.75 pmol kg−1 min−1, n = 9) or NaCl for 180 min with a radionuclide-labeled omelette and fruit punch (370 kcal). Outcome measures were gastric emptying rate, insulinogenic index, hunger, satiety, desire to eat, and prospective food consumption. Blood was analyzed for GIP, GLP-1, glucagon, C-peptide, peptide YY (PYY) and ghrelin. Key Results Glucose-dependent insulinotropic polypeptide 2 and 5 pmol kg−1 min−1 decreased gastric half-emptying time from 128.5 ± 34.0 min in controls to 93.3 ± 6.3 and 85.2 ± 11.0 min (P < 0.05). Glucose-dependent insulinotropic polypeptide 5 pmol kg−1 min−1 decreased postprandial glucose (P < 0.001) and insulin (P < 0.05) with increased insulinogenic index. Glucose-dependent insulinotropic polypeptide had no effects on hunger, desire to eat, satiety or prospective consumption. Glucagon-like peptide-1 0.75 pmol kg−1 min−1 increased half-emptying time from 76.6 ± 7.6 min to 329.4 ± 71.6 (P < 0.01). Glucagon-like peptide-1 decreased plasma glucose and insulin (both P < 0.05–0.001), and increased insulinogenic index markedly. Hunger, desire to eat and prospective consumption were decreased (P < 0.05), and satiety borderline increased (P < 0.06). Conclusion & Inferences The incretin effect of GIP and GLP-1 differs as GLP-1 exerts a strong glucoregulatory incretin through inhibition of gastric emptying, which GIP does not. Thus, GLP-1 as incretin mimetic may offer unique benefits in terms of weight loss in treatment of type 2 diabetes.
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| 6. |
- Linder, Gustav, et al.
(författare)
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Burden of in-hospital care in oesophageal cancer : national population-based study
- 2021
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Ingår i: BJS Open. - : Oxford University Press (OUP). - 2474-9842. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oesophageal cancer management requires extensive in-hospital care. This cohort study aimed to quantify in-hospital care for patients with oesophageal cancer in relation to intended treatment, and to analyse factors associated with risk of spending a large proportion of survival time in hospital. METHODS: All patients with oesophageal cancer in three nationwide registers over a 10-year period were included. In-hospital care during the first year after diagnosis was evaluated, and the proportion of survival time spent in hospital, stratified by intended treatment (curative, palliative or best supportive care), was calculated. Associations between relevant factors and a greater proportion of survival time in hospital were analysed by multivariable logistic regression. RESULTS: In-hospital care was provided for a median of 39, 26, and 15 days in the first year after diagnosis of oesophageal cancer in curative, palliative, and best supportive care groups respectively. Patients receiving curatively intended treatment spent a median of 12 per cent of their survival time in hospital during the first year after diagnosis, whereas those receiving palliative or best supportive care spent 19 and 23 per cent respectively. Factors associated with more in-hospital care included older age, female sex, being unmarried, and chronic obstructive pulmonary disease. CONCLUSION: The burden of in-hospital care during the first year after diagnosis of oesophageal cancer was substantial. Important clinical and socioeconomic factors were identified that predisposed to a greater proportion of survival time spent in hospital.
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| 7. |
- Cordomi, Arnau, et al.
(författare)
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Effect of different treatments of long-range interactions and sampling conditions in molecular dynamic simulations of rhodopsin embedded in a dipalmitoyl phosphatidylcholine bilayer
- 2007
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Ingår i: Journal of Computational Chemistry. - : Wiley. - 0192-8651 .- 1096-987X. ; 28:6, s. 1017-1030
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Forskningsöversikt (refereegranskat)abstract
- The present study analyzes the effect of the simulation conditions on the results of molecular dynamics simulations of G-protein coupled receptors (GPCRs) performed with an explicit lipid bilayer. Accordingly, the present work reports the analysis of different simulations of bovine rhodopsin embedded in a dipalmitoyl phosphatidylcholine (DPPC) lipid bilayer using two different sampling conditions and two different approaches for the treatment of long-range electrostatic interactions. Specifically, sampling was carried out either by using the statistical ensembles NVT or NPT (constant number of atoms, a pressure of 1 arm in all directions and fixed temperature), and the electrostatic interactions were treated either by using a twin-cutoff, or the particle mesh Ewald summation method (PME). The results of the present study suggest that the use of the NPT ensemble in combination with the PME method provide more realistic simulations. The use of NPT during the equilibration avoids the need of an a priori estimation of the box dimensions, giving the correct area per lipid. However, once the system is equilibrated, the simulations are irrespective of the sampling conditions used. The use of an electrostatic cutoff induces artifacts on both lipid thickness and the ion distribution, but has no direct effect on the protein and water molecules.
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| 8. |
- Cordomi, Arnau, et al.
(författare)
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Effect of Force Field Parameters on Sodium and Potassium Ion Binding to Dipalmitoyl Phosphatidylcholine Bilayers
- 2009
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 5:8, s. 2125-2134
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Tidskriftsartikel (refereegranskat)abstract
- The behavior of electrolytes in molecular dynamics simulations of zwitterionic phospholipid bilayers; is very sensitive to the force field parameters used. Here, several 200 ns molecular dynamics of simulations of dipalmitoyl phosphotidylcholine (PC) bilayers in 0.2 M sodium or potassium chloride using various common force field parameters for the cations are presented. All employed parameter sets give a larger number of Na+ ions than K+ ions that bind to the lipid heads, but depending on the parameter choice quite different results are seen. A wide range of coordination numbers for the Na+ and K+ ions is also observed. These findings have been analyzed and compared to published experimental data. Some simulations produce aggregates of potassium chloride, indicating (in accordance with published simulations) that these force fields do not reproduce the delicate balance between salt and solvated ions. The differences between the force fields can be characterized by one single parameter, the electrostatic radius of the ion, which is correlated to sigma(MO) (M represents Na+/K+), the Lennard-Jones radius. When this parameter exceeds a certain threshold, binding to the lipid heads is no longer observed. One would, however, need more accurate experimental data to judge or rank the different force fields precisely. Still, reasons for the poor performance of some of the parameter sets are clearly demonstrated, and a quality control. procedure is provided.
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| 9. |
- Cordomi, Arnau, et al.
(författare)
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Effect of ions on a dipalmitoyl phosphatidylcholine bilayer. A molecular dynamics simulation study
- 2008
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 112:5, s. 1397-1408
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Tidskriftsartikel (refereegranskat)abstract
- The effect of physiological concentrations of different chlorides on the structure of a dipalmitoyl phosphatidylcholine (DPPC) bilayer has been investigated through atomistic molecular dynamics simulations. These calculations provide support to the concept that Li+, Na+, Ca2+, Mg2+, Sr2+, Ba2+, and Ac3+, but not K+, bind to the lipid-head oxygens. Ion binding exhibits an influence on lipid order, area per lipid, orientation of the lipid head dipole, the charge distribution in the system, and therefore the electrostatic potential across the head-group region of the bilayer. These structural effects are sensitive to the specific characteristics of each cation, i.e., radius, charge, and coordination properties. These results provide evidence aimed at shedding some light into the apparent contradictions among different studies reported recently regarding the ordering effect of ions on zwitterionic phosphatidylcholine lipid bilayers.
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| 10. |
- Edholm, Olle, et al.
(författare)
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Areas of molecules in membranes consisting of mixtures
- 2005
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 89:3, s. 1827-1832
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Tidskriftsartikel (refereegranskat)abstract
- The question has arisen in recent literature: how to partition the total area in simulations of membranes consisting of more than one kind of molecule into average areas for each kind of molecule. Several definitions have been proposed, each of which has arbitrary features. When applied to mixtures of cholesterol and DPPC, these definitions give different results. This note recalls that physical chemistry provides a canonical way to de. ne molecular area, in analogy to the definition of partial-specific volume. Results for partial-specific area are obtained from simulations of DPPC/cholesterol bilayers and compared to the results from the other recent definitions. The partial-specific-area formalism dramatically demonstrates the condensing effect of cholesterol and this leads to the introduction of a specific model that accounts for the area of mixtures of cholesterol and lipid over the entire range of cholesterol concentrations.
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