| 1. |
- Lewin, N. L., et al.
(författare)
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Influence of single nucleotide polymorphisms among cigarette smoking and non-smoking patients with coronary artery disease, urinary bladder cancer and lung cancer
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Cigarette smoke is suggested to be a risk factor for coronary artery disease (CAD), urinary bladder cancer (UBCa) or lung cancer (LCa). However, not all heavy smokers develop these diseases and elevated cancer risk among first-degree relatives suggests an important role of genetic factor. Methods Three hundred and ten healthy blood donors (controls), 98 CAD, 74 UBCa and 38 LCa patients were included in this pilot study. The influence of 92 single nucleotide polymorphisms (SNPs) and impact of cigarette smoking were analysed. Results Out of 92 SNPs tested, differences in distribution of 14 SNPs were detected between controls and patient groups. Only CTLA4 rs3087243 showed difference in both CAD and UBCa patient group compared to control group. Stratified by smoking status, the impact of smoking was associated to frequencies of 8, 3 and 4 SNPs in CAD, UBCa, LCa patients, respectively. None of these 92 SNPs showed a statistically significant difference to more than one type of disease among smoking patients. In non-smoking patients, 7, 3 and 6 SNPs were associated to CAD, UBCa, LCa, respectively. Out of these 92 SNPs, CTLA4 rs3087243 was associated to both non-smoking CAD and UBCa. The XRCC1 rs25487 was associated to both non-smoking UBCa and LCa. Conclusion SNPs might be important risk factors for CAD, UBCa and LCa. Distribution of the SNPs was specific for each patient group, not a random event. Impact of cigarette smoking on the disease was associated to the specific SNP sequences. Thus, smoking individuals with SNPs associated to risk of these serious diseases is an important target group for smoking cessation programs.
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| 2. |
- Håkansson, P, et al.
(författare)
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Ontogenetic development and spatial distribution of the ileal apical sodium-dependent bile acid transporter and the ileal lipid-binding protein in apoE knockout and C57BL/6 mice
- 2002
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 37:9, s. 1089-1096
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although apoE-/- mice are characterized by hypercholesterolemia, the bile acid enterohepatic circulation, which plays a crucial role in cholesterol homeostasis, has not been examined in these mice. The differences between apoE-/- and C57BL/6 mice in expression of the ileal ASBT and ILBP and in intestinal bile acid absorption were studied.METHODS: The intestinal tissues of the fetal, neonatal and post-weaning mice were processed for immunohistochemistry. Body retention and fecal excretion of 75SeHCAT were measured. The bile acid pool size and its composition were analysed by HPLC.RESULTS: In apoE-/- and C57BL/6 mice, the bile acid pool size was 75 +/- 13 and 78 +/- 13 micromol/ 100 g body weight, respectively, while the ratio of cholic acid/beta-muricholic acid was 1.8 +/- 0.3 and 1.4 +/- 0.3 (P < 0.05), respectively. The daily body retention of 75SeHCAT was 48% = 1.8% in C57 black mice and 58.4% +/- 2.7% in apoE-/- mice (P < 0.05). In both mouse strains, ASBT expression in the small intestine was found in the near-term fetal and post-weaning mice, while ILBP expression was found in all postnatal mice. In the post-weaning mice, ILBP expression was limited to the distal 25%-30% of the small intestine, while ASBT expression was limited to the distal 18%.CONCLUSIONS: The bile acid enterohepatic circulation in apoE-/- mice probably does not differ greatly from that in C57BL/6 mice.
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| 3. |
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| 4. |
- van Buggenhout, Sandra, et al.
(författare)
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Structural design of natural plant based foods to promote nutritional quality
- 2012
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Ingår i: Trends in Food Science and Technology. - : Elsevier BV. - 0924-2244 .- 1879-3053. ; 24:1, s. 47-59
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- During traditional industrial processing of fruit and vegetable derived foods, consideration of the eventual retention, bio-accessibility or bio-availability of nutrients has hitherto been a secondary priority. Indeed standard processing of soups and sauces involves treating all ingredients in a similar way, usually by prolonged heat treatment and results in both lowered nutritional value and sensory quality of food products. Such products are typically structured using various additives including starches, gums and stabilizers, which consumers regard as unnatural, rather than exploiting the endogenous structuring potential of the fruit and vegetable ingredients as available at the farm gate. Recent studies undertaken within the EU sponsored 'Healthy Structuring' project have shown how to design an industrially manufactured product with good sensory qualities that is natural and nutritious. The strategy has been to use the inherent structural and nutritional properties of the raw material ingredients, on the one hand to ensure the textural quality of the final product without the use of artificial gums or stabilizers and, on the other hand to optimize the nutritional quality of the final product. This review briefly summarizes both the approach taken and the results obtained within the project.
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| 5. |
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| 6. |
- Bull, Peter, et al.
(författare)
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Förstudie obemannade farkoster
- 2012
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Rapport (populärvet., debatt m.m.)abstract
- Obemannade farkoster används allt oftare, och i allt fler roller, i dagens kon- flikter. Denna rapport ger en bred överblick över området militära obemannade farkoster, samt rekommendationer för inriktningen av framtida FoU-satsningar inom området.Överblicken över området har fokus på både system, förmågor och verksam- heter som är relevanta för Försvarsmakten. Genom att låta de insatsförmågor som definieras i FMUP (Försvarsmaktens utvecklingsplan) gå som en röd tråd genom rapporten, både när specifika system diskuteras och när möjliga scena- rier där obemannade farkoster kan vara till nytta beskrivs, har vi försökt hålla både bredd och relevans i dokumentet.Rekommendationerna vilar på en genomgång av de inriktningsdokument som producerats i Försvarsmakten, t.ex. Perspektivplanneringen och FMUP, besök vid de enheter som dagligen använder obemannade farkoster, UAV-enheten i Karlsborg och Swedec i Eksjö, samt den områdesöverblick som nämns ovan. Slutsatserna är att den effektivaste kompetensuppbyggnaden och kunskapsöver- föringen fås om man skapar breda tvärvetenskapliga projekt inom respektive systemkategori (UAV, UGV, etc) med nära kontakter till materielförsörjnings- processen och perspektivplaneringen. Dessa kan samla kompetensen inom FHS och FOI, övervaka forskningsfronten genom att bevaka tävlingar, konferenser samt delta i internationella samarbeten, samt överföra det samlade resultaten till Försvarsmakten genom demonstrationer av verkliga eller simulerade delsy- stem och interaktiva simuleringar av hela system. Just systemsimuleringar kan göras särskilt realistiska, eftersom interaktionen med de riktiga obemannade systemen till stor del sker igenom kontrollstationernas datorer. På så sätt ska- pas en känsla för både hot och möjligheter med de nya systemen, vilket gagnar både taktikutveckling och materielprocesser.
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| 7. |
- Bäckström, Torbjörn, et al.
(författare)
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Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons
- 2011
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Ingår i: Neuroscience. - Oxford : Elsevier BV. - 0306-4522 .- 1873-7544. ; 191:Special issue, s. 46-54
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Forskningsöversikt (refereegranskat)abstract
- Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane C1(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote disinhibition, and hence excitability. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain. (C) 2011 Published by Elsevier Ltd on behalf of IBRO.
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| 8. |
- Denison, H, et al.
(författare)
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Diacylglycerol acyltransferase 1 inhibition with AZD7687 alters lipid handling and hormone secretion in the gut with intolerable side effects : a randomized clinical trial
- 2014
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Ingår i: Diabetes, obesity and metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 16:4, s. 334-343
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Tidskriftsartikel (refereegranskat)abstract
- AIM:Inhibition of diacylglycerol acyltransferase 1 (DGAT1) is a potential treatment modality for patients with type 2 diabetes mellitus and obesity, based on preclinical data suggesting it is associated with insulin sensitization and weight loss. This randomized, placebo-controlled, phase 1 study in 62 overweight men explored the effects and tolerability of AZD7687, a reversible and selective DGAT1 inhibitor.METHODS:Multiple doses of AZD7687 (1, 2.5, 5, 10 and 20 mg/day, n = 6 or n = 12 for each) or placebo (n = 20) were administered for 1 week. Postprandial serum triacylglycerol (TAG) was measured for 8 hours after a standardized 45% fat meal. Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were measured and a paracetamol challenge was performed to assess gastric emptying.RESULTS:Dose-dependent reductions in postprandial serum TAG were demonstrated with AZD7687 doses ≥5 mg compared with placebo (p < 0.01). Significant (p < 0.001) increases in plasma GLP-1 and PYY levels were seen at these doses, but no clear effect on gastric emptying was demonstrated at end of treatment. With AZD7687doses >5 mg/day, gastrointestinal (GI) side effects increased; 11/18 of these participants discontinued treatment owing to diarrhoea.CONCLUSIONS:Altered lipid handling and hormone secretion in the gut were demonstrated during 1-week treatment with the DGAT1 inhibitor AZD7687. However, the apparent lack of therapeutic window owing to GI side effects of AZD7687, particularly diarrhoea, makes the utility of DGAT1 inhibition as a novel treatment for diabetes and obesity questionable.
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| 9. |
- Denison, H, et al.
(författare)
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Proof of mechanism for the DGAT1 inhibitor AZD7687 : results from a first-time-in-human single-dose study
- 2013
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Ingår i: Diabetes, obesity and metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 15:2, s. 136-143
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Inhibition of diacylglycerol acyltransferase 1 (DGAT1), which catalyses the final step in triacylglycerol (TAG) assembly, is suggested as a treatment for type 2 diabetes and obesity based on animal data indicating insulin sensitization and weight reduction. This first-time-in-human single ascending dose study explored the safety, tolerability, pharmacokinetics and pharmacodynamics of the selective DGAT1 inhibitor AZD7687.METHODS: Eighty healthy male subjects were enrolled. In each of 10 cohorts, six subjects received the same dose of AZD7687 orally (range across cohorts 1-60 mg) and two placebo. Plasma AZD7687 exposure was measured repeatedly. Postprandial serum TAG excursion was measured during 8 h after a standardized mixed meal with fat energy content of 60% (SMM 60%; five cohorts, 1-20 mg), before (baseline) and after dosing, to assess effects on gut DGAT1 activity.RESULTS: AZD7687 markedly reduced postprandial TAG excursion with a steep concentration-effect relationship. Incremental TAG AUC (area under the serum concentration vs. time curve) following SMM 60% was decreased >75% from baseline at doses ≥5 mg (p < 0.0001 vs. placebo). Serum levels of diacylglycerol, specifically measured with mass spectrometry, did not increase after AZD7687 administration. Nausea, vomiting and diarrhoea were reported with increasing doses and they limited dose escalation. Lowering of SMM fat content to 45 or 30% in five cohorts gradually reduced the frequency of gastrointestinal symptoms at a given dose of AZD7687.CONCLUSIONS: The attenuating effect of AZD7687 on postprandial TAG excursion provides proof of mechanism with respect to gut DGAT1 inhibition. However, dose and diet-related gastrointestinal side effects may impact further development of DGAT1 inhibitors.
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| 10. |
- Diogo Löfgren, Christina, et al.
(författare)
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The Challenge of Measuring Viscoelastic Properties of Human Whole Saliva to Fit Clinical Purpose
- 2015
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Ingår i: International Journal of Oral and Dental Health. - : ClinMed International. - 2469-5734. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- To understand the protective functions of saliva secreted from different glands in the masticatory process, it is of interest to study its viscoelastic properties. Characterization of saliva samples are not that easily performed in a clinical setting, since most of the experimental techniques and instruments available are developed for research purposes. The aim of this study was to characterize how the viscoelastic properties of saliva can be measured and monitored using two laboratory instruments. Unstimulated whole saliva from 11 healthy volunteers was characterized using two instruments, an ARES-G2 rheometer and a Bohlin Oscillating Cup Rheometer. Measurements performed on unstimulated human whole saliva showed that the ARES rheometer will in linear viscoelastic conditions of the sample give absolute viscoelastic numbers of undisturbed saliva whilst the BOCR can be used to give an indication of gel strength, gel formation, and gel stability in viscoelastic samples being sheared in their non-linear viscoelastic region by introducing a Saliva Gel Strength Index, SGSI. Both methods clearly illustrate the presence of viscoelastic properties in saliva.
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