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- Rosenstock, J, et al.
(författare)
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Effects of the DPP-4 Inhibitor Vildagliptin on Incretin Hormones, Islet Function, and Postprandial Glycemia in Subjects with Impaired Glucose Tolerance
- 2008
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 31:1, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT). Research Design and Methods: A 12-week double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 179 subjects with IGT (2-h glucose= 9.1 mmol/l, A1C= 5.9%). Plasma levels of intact GLP-1 and GIP, glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and Week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin - placebo) in the adjusted mean changes from baseline to endpoint in the total and incremental (Delta) AUC(0-2h) for these analytes were assessed by ANCOVA; glucose AUC(0-2h) was the primary outcome variable. Results: Relative to placebo, vildagliptin increased GLP-1 (DeltaAUC, +6.0+/-1.2 pmol/l*h, P<0.001) and GIP (DeltaAUC, +46.8+/-5.4 pmol/l*h, P<0.001) and decreased glucagon (DeltaAUC, -3.0 +/- 1.0 pmol/l*h, P=0.003). Although postprandial insulin levels were unaffected (DeltaAUC, +20.8+/-35.7 pmol/l*h, P=0.561), prandial glucose excursions were reduced (DeltaAUC, -1.0+/-0.3 mmol/l*h, P<0.001), representing approximately 30% decrease relative to placebo. Beta-cell function as assessed by the ISR AUC(0-2h)/glucose AUC(0-2h) was significantly increased (+6.4 +/- 2.0 pmol*min(-1)*m(-2)*mM(-1), P=0.002). Adverse event profiles were similar in the two treatment groups and no hypoglycemia was reported. Conclusions: The known effects of vildagliptin on incretin levels and islet function in type 2 diabetes were reproduced in subjects with IGT with a 32% reduction in postprandial glucose excursions and no evidence of hypoglycemia or weight gain.
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- Asplund, M, et al.
(författare)
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Toxicity evaluation of PEDOT/biomolecular composites intended for neural communication electrodes
- 2009
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Ingår i: BIOMEDICAL MATERIALS. - : IOP Publishing. - 1748-6041 .- 1748-605X. ; 4:4, s. 045009-
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Tidskriftsartikel (refereegranskat)abstract
- Electrodes coated with the conducting polymer poly(3,4-ethylene dioxythiophene) (PEDOT) possess attractive electrochemical properties for stimulation or recording in the nervous system. Biomolecules, added as counter ions in electropolymerization, could further improve the biomaterial properties, eliminating the need for surfactant counter ions in the process. Such PEDOT/biomolecular composites, using heparin or hyaluronic acid, have previously been investigated electrochemically. In the present study, their biocompatibility is evaluated. An agarose overlay assay using L929 fibroblasts, and elution and direct contact tests on human neuroblastoma SH-SY5Y cells are applied to investigate cytotoxicity in vitro. PEDOT: heparin was further evaluated in vivo through polymer-coated implants in rodent cortex. No cytotoxic response was seen to any of the PEDOT materials tested. The examination of cortical tissue exposed to polymer-coated implants showed extensive glial scarring irrespective of implant material (Pt:polymer or Pt). However, quantification of immunological response, through distance measurements from implant site to closest neuron and counting of ED1+ cell density around implant, was comparable to those of platinum controls. These results indicate that PEDOT: heparin surfaces were non-cytotoxic and show no marked difference in immunological response in cortical tissue compared to pure platinum controls.
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- Guldstrand, M., et al.
(författare)
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Dissociated incretin response to oral glucose at 1 year after restrictive vs. malabsorptive bariatric surgery
- 2009
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Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 11:11, s. 1027-1033
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Tidskriftsartikel (refereegranskat)abstract
- Aim Compare the response to oral glucose of the two incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) at 1 year after restrictive vs. malabsorptive bariatric surgery. Methods Vertical banded gastroplasty (VBG, n = 7) or jejunoileal bypass (JIB, n = 5) was performed in 12 women, aged 26-39 years, with severe obesity [body mass index (BMI) 46.6 +/- 2.3 kg/m2]. After 1 year, 75 g glucose was administered and plasma levels of glucose, insulin, GIP and GLP-1 were determined regularly during the following 2 h. Results At 1 year after operation, reduction in body weight, actual body weight, fasting glucose or insulin, or the glucose and insulin responses to oral glucose did not differ significantly between the groups. Similarly, fasting GIP and GLP-1 levels did not differ significantly between the groups. In contrast, the GIP and GLP-1 responses to oral glucose were different between the groups in a dissociated pattern. Thus, AUC(GIP) was significantly higher after VBG than after JIB (53 +/- 8 vs. 26 +/- 6 pmol/l/min, p = 0.003). In contrast, AUC(GLP-1) was significantly higher after JIB than after VBG (49 +/- 5 vs. 20 +/- 3 pmol/l/min, p = 0.007). Conclusions We conclude that at 1 year after bariatric surgery, the two incretins show dissociated responses in that the GIP secretion is higher after VBG whereas GLP-1 secretion is higher after JIB. This dissociated incretin response is independent from reduction in body weight, glucose tolerance or insulin secretion.
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- 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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- Holmberg, Anna, et al.
(författare)
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Biofilm formation by Propionibacterium acnes is a characteristic of invasive isolates
- 2009
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 15:8, s. 787-795
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Tidskriftsartikel (refereegranskat)abstract
- Propionibacterium acnes is a common and probably underestimated cause of delayed joint prosthesis infection. Bacterial biofilm formation is central in the pathogenesis of infections related to foreign material, and P. acnes has been shown to form biofilm both in vitro and in vivo. Here, biofilm formation by 93 P. acnes isolates, either from invasive infections (n = 45) or from the skin of healthy people (n = 48), was analysed. The majority of isolates from deep infections produced biofilm in a microtitre model of biofilm formation, whereas the skin isolates were poor biofilm producers (p <0.001 for a difference). This indicates a role for biofilm formation in P. acnes virulence. The type distribution, as determined by sequencing of recA, was similar among isolates isolated from skin and from deep infections, demonstrating that P. acnes isolates with different genetic backgrounds have pathogenic potential. The biofilm formed on plastic and on bone cement was analysed by scanning electron microscopy (EM) and by transmission EM. The biofilm was seen as a 10-mum-thick layer covering the bacteria and was composed of filamentous as well as more amorphous structures. Interestingly, the presence of human plasma in solution or at the plastic surface inhibits biofilm formation, which could explain why P. acnes primarily infect plasma-poor environments of, for example, joint prostheses and cerebrospinal shunts. This work underlines the importance of biofilm formation in P. acnes pathogenesis, and shows that biofilm formation should be considered in the diagnosis and treatment of invasive P. acnes infections.
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| 13. |
- Lindblad, Bengt, et al.
(författare)
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Reversal of Anticoagulation : Protamine
- 2009
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Ingår i: Pharmacology in the Catheterization Laboratory. - Oxford, UK : Wiley-Blackwell. - 9781405157049 - 9781444306347 ; , s. 287-293
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Bokkapitel (refereegranskat)
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| 15. |
- Mordaka, J., et al.
(författare)
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The importance of rotational kinematics in pedestrian head to windshield impacts
- 2007
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Ingår i: International Research Council on the Biomechanics of Injury - 2007 International IRCOBI Conference on the Biomechanics of Injury, Proceedings. - 2951421087 - 9782951421080 ; , s. 83-94
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Konferensbidrag (refereegranskat)abstract
- The objective of the present study was to analyze the effect of angular kinematics on head injury in pedestrian head-to-windshield impacts. Three cases of pedestrian head impacts were simulated with FE head and windshield models. The initial impact conditions were obtained from pedestrian accident reconstructions carried out using multi-body pedestrian and car models. The results from the FE head model were compared with injuries reported in the database. Maximum principal strain was chosen as the injury indicator. After successful head injury predictions, the initial velocities were varied and as a result different peak angular velocities and accelerations were simulated. The results showed that increased peak change in angular velocity caused higher maximal principal strain in the brain and in consequence higher probability of Diffuse Axonal Injury (DAI), and Acute Subdural Haematoma (ASDH). A dramatic, three-fold increase in the strain levels in the brain was found when doubling the impact velocity. This paper presents work performed within the framework of a European Commission 6 th framework project (APROSYS).
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- Mårtensson, Olof, et al.
(författare)
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Fermented, ropy, oat-based products reduce cholesterol levels and stimulate the bifidobacteria flora in humans
- 2005
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Ingår i: Nutrition Research. - : Elsevier BV. - 0271-5317. ; 25:5, s. 429-442
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Tidskriftsartikel (refereegranskat)abstract
- This investigation determined the effects of fermented oat-based products containing both native and microbial beta-glucans on plasma lipids and on fecal total bacterial count and Bifidobacterium ssp. The study was randomized, double blind with 3 parallel groups. Sixty-two free-living volunteers with moderately increased plasma cholesterol levels were recruited. In the final analysis, 56 subjects remained, as 6 subjects had left the study either due to lack of time (n = 2), unwillingness to continue the regimen (n = 2), or for other reasons (n = 2). During the first 3 weeks, all subjects received a fermented dairy-based product (control product, run-in period). On the following 5 weeks, I group continued with the control product, whereas the other 2 groups were given fermented oat-based products (intervention period, 3-3.5 g native beta-glucans per day). One of the oat products (ropy) was cofermented with an exopolysaccharide-producing strain, Pediococcus damnosus 2.6. A significant (P = .022) reduction in total cholesterol by 6% was observed in volunteers who had eaten the fermented, ropy, oat-based product compared with the control group. No other significant changes in plasma lipids were found. A significant increase in total bacterial count (P = .001) and Bifidobacterium ssp (P = .012) was observed in fecal samples from volunteers in the group who had eaten the fermented, ropy, oat-based product. This study shows that a fermented, ropy, oat-based product, containing both native and microbial glucans, can reduce the blood cholesterol level and also stimulate the bifidobacteria flora in the gastrointestinal tract. (c) 2005 Elsevier Inc. All rights reserved.
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