| 1. |
- Albertsson, Per-Åke, et al.
(författare)
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Chloroplast membranes retard fat digestion and induce satiety: effect of biological membranes on pancreatic lipase/co-lipase
- 2007
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Ingår i: Biochemical Journal. - 0264-6021. ; 401, s. 727-733
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Tidskriftsartikel (refereegranskat)abstract
- Human obesity is a global epidemic, which causes a rapidly increased frequency of diabetes and cardiovascular disease. One reason for obesity is the ready availability of refined food products with high caloric density, an evolutionarily new event, which makes over-consumption of food inevitable. Fat is a food product with high caloric density. The mechanism for regulation of fat intake has therefore been studied to a great extent. Such studies have shown that, as long as fat stays in the intestine, satiety is promoted. This occurs through the fat-released peptide hormones, the best known being CCK (cholecystokinin), which is released by fatty acids. Hence, retarded fat digestion with prolonged time for delivery of fatty acids promotes satiety. Pancreatic lipase, together with its protein cofactor, co-lipase, is the main enzymatic system responsible for intestinal fat digestion. We found that biological membranes, isolated from plants, animals or bacteria, inhibit the lipase/co-lipase-catalysed hydrolysis of triacylglycerols even in the presence of bile salt. We propose that the inhibition is due to binding of lipase/co-lipase to the membranes and adsorption of the membranes to the aqueous/triacylglycerol interface, thereby hindering lipase/co-lipase from acting on its lipid substrate. We also found that chloroplast membranes (thylakoids), when added to refined food, suppressed food intake in rats, lowered blood lipids and raised the satiety hormones, CCK and enterostatin. Consequently, the mechanism for satiety seems to be retardation of fat digestion allowing the fat products to stay longer in the intestine.
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| 2. |
- Arvidsson, Per-Ola, et al.
(författare)
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Violaxanthin accessibility and temperature dependency for de-epoxidation in spinach thylakoid membranes
- 1997
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Ingår i: Photosynthesis Research. - 0166-8595. ; 52:1, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- Using DTT and iodoacetamide as a novel irreversible method to inhibit endogenous violaxanthin de-epoxidase, we found that violaxanthin could be converted into zeaxanthin from both sides of the thylakoid membrane provided that purified violaxanthin de-epoxidase was added. The maximum conversion was the same from both sides of the membrane. Temperature was found to have a strong influence both on the rate and degree of maximal violaxanthin to zeaxanthin conversion. Thus only 50% conversion of violaxanthin was detected at 4 degreesC, whereas at 25 degreesC and 37 degreesC the degree of conversion was 70% and 80%, respectively. These results were obtained with isolated thylakoids from non-cold acclimated leafs. Pigment analysis of sub-thylakoid membrane domains showed that violaxanthin was evenly distributed between stroma lamellae and grana partitions. This was in contrast to chlorophyll a and beta-carotene which were enriched in stroma lamellae fractions while chlorophyll b, lutein and neoxanthin were enriched in the grana membranes. In combination with added violaxanthin de-epoxidase we found almost the same degree of conversion of violaxanthin to zeaxanthin (73-78%) for different domains of the thylakoid membrane. We conclude that violaxanthin de-epoxidase converts violaxanthin in the lipid matrix and not at the proteins, that violaxanthin does not prefer one particular membrane region or one particular chlorophyll protein complex, and that the xanthophyll cycle pigments are oriented in a vertical manner in order to be accessible from both sides of the membrane when located in the lipid matrix.
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| 3. |
- Chamalidou, Chaido, 1972, et al.
(författare)
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Survival patterns of invasive lobular and invasive ductal breast cancer in a large population-based cohort with two decades of follow up
- 2021
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Ingår i: Breast. - : Churchill Livingstone. - 0960-9776 .- 1532-3080. ; 59, s. 294-300
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Tidskriftsartikel (refereegranskat)abstract
- Background: Invasive lobular carcinoma (ILC) comprises 8-15 % of all invasive breast cancers and large population-based studies with >10 years of follow-up are rare. Whether ILC has a long-time prognosis different from that of invasive ductal carcinoma, (IDC) remains controversial. Purpose: To investigate the excess mortality rate ratio (EMRR) of patients with ILC and IDC and to correlate survival with clinical parameters in a large population-based cohort. Material and methods: From 1989 through 2006, we identified 17,481 patients diagnosed with IDC (n = 14,583) or ILC (n = 2898), younger than 76 years from two Swedish Regional Cancer Registries. Relative survival (RS) during 20 years of follow up was analysed. Results: ILC was significantly associated with older age, larger tumours, ER positivity and well differentiated tumours. We noticed an improved survival for patients with ILC during the first five years, excess mortality rate ratio (EMRR) 0.64 (CI 95 % 0.53-0.77). This was shifted to a significant decreased survival 10-15 years after diagnosis (EMRR 1.49, CI 95 % 1.16-1.93). After 20 years the relative survival rates were similar, 0.72 for ILC and 0.73 for IDC. Conclusions: During the first five years after surgery, the EMRR was lower for patients with ILC as compared to patients with IDC, but during the years 10-15 after surgery, we observed an increased EMRR for patients with ILC as compared to IDC. These EMRR between ILC and IDC were statistically significant but the absolute difference in excess mortality between the two groups was small. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 4. |
- Edsparr, Karin, 1979, et al.
(författare)
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Effects of IL-2 on MMP expression in freshly isolated human NK cells and the IL-2-independent NK cell line YT.
- 2010
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Ingår i: Journal of immunotherapy (Hagerstown, Md. : 1997). - 1537-4513. ; 33:5, s. 475-81
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-2 is an important activation factor for natural killer (NK) cells but its effect on NK cell matrix metalloproteinases (MMP) production and matrix degradation is less well investigated. We have used freshly isolated human NK cells and the IL-2-independent NK cell line, YT, to investigate the effects of IL-2 stimulation on NK cell invasion of Matrigel and on MMP expression and production. In YT cells, we found opposing early and late effects of IL-2 stimulation with an early (2 h) increase in MMP-9 protein level and enhanced migration in the Matrigel invasion assay and by 30 hours a decreased mRNA expression of MMP-2, MMP-9, MMP-13, MT3-MMP, and MT6-MMP. We also found a preculture period of 48 hours with IL-2 to negatively affect YT cell migration. We furthermore found that freshly isolated human NK cells Matrigel invasion was MMP-dependent and it increased in response to IL-2. Importantly, in freshly isolated human NK cells we did not see a downregulation of MMPs after 24 hours IL-2 stimulation, but instead a significant upregulation of MT6-MMP mRNA. Because of the cellular localisation of MT6-MMP, which ensures a focalized proteolytic activity, and its high expression compared with the other MMPs in freshly isolated human NK cells makes it of interest to study further.
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| 5. |
- Edsparr, Karin, 1979, et al.
(författare)
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Human NK cell lines migrate differentially in vitro related to matrix interaction and MMP expression.
- 2009
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Ingår i: Immunology and cell biology. - : Wiley. - 1440-1711 .- 0818-9641. ; 87:6, s. 489-95
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Tidskriftsartikel (refereegranskat)abstract
- Matrix metalloproteinases (MMPs) are thought to be of importance for the migratory ability of natural killer (NK) cells. Their expression and production may influence the amount of tumour-infiltrating NK cells and thereby any therapeutic capability. In this study, we sought to investigate the importance of MMPs for human NK cells' ability to degrade and migrate through the extracellular matrix (ECM). The two human NK cell lines, NK-92 and YT, migratory ability, MMP expression and production as well as their morphological appearance when cultured in the ECM equivalent Matrigel were analysed and compared. The quantitatively more migratory NK-92 cells were found to express invadopodia/podosomes at a significantly higher degree when cultured in Matrigel and gave rise to a general disintegration of the Matrigel. The NK-92 cells had a higher mRNA expression of MMP-2, -9, -13, MT1-, MT3- and MT6-MMP and a significantly higher production of MMP-9 compared to YT cells. These differences could explain the substantial functional difference observed between the two cell lines with respect to migratory capacity. In addition, the number of Matrigel invading NK-92 cells decreased significantly in the presence of the MMP inhibitor GM6001, demonstrating that MMPs have a critical function in their migration.
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| 6. |
- Edsparr, Karin, 1979, et al.
(författare)
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Matrix metalloproteinases in cytotoxic lymphocytes impact on tumour infiltration and immunomodulation.
- 2011
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Ingår i: Cancer microenvironment : official journal of the International Cancer Microenvironment Society. - : Springer Science and Business Media LLC. - 1875-2284. ; 4:3, s. 351-60
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Tidskriftsartikel (refereegranskat)abstract
- To efficiently combat solid tumours, endogenously or adoptively transferred cytotoxic T cells and natural killer (NK) cells, need to leave the vasculature, traverse the interstitium and ultimately infiltrate the tumour mass. During this locomotion and migration in the three dimensional environment many obstacles need to be overcome, one of which is the possible impediment of the extracellular matrix. The first and obvious one is the sub-endothelial basement membrane but the infiltrating cells will also meet other, both loose and tight, matrix structures that need to be overridden. Matrix metalloproteinases (MMPs) are believed to be one of the most important endoprotease families, with more than 25 members, which together have function on all known matrix components. This review summarizes what is known on synthesis, expression patterns and regulation of MMPs in cytotoxic lymphocytes and their possible role in the process of tumour infiltration. We also discuss different functions of MMPs as well as the possible use of other lymphocyte proteases for matrix degradation.
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| 7. |
- Emek, Sinan C, et al.
(författare)
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A large scale method for preparation of plant thylakoids for use in body weight regulation.
- 2010
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Ingår i: Preparative biochemistry & biotechnology. - : Informa UK Limited. - 1532-2297 .- 1082-6068. ; 40:1, s. 13-27
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Tidskriftsartikel (refereegranskat)abstract
- A method for preparation of thylakoids from plant leaves on a large scale is described. The method involves: 1) disruption of the cells with a blender followed by filtration to remove large cell debris and non disrupted cells. 2) precipitation of the thylakoids by adjusting the pH to the isoelectric point, pH 4.7. 3) a washing step by dilution of the precipitate in water followed by precipitation at the same pH. 4) concentration of the precipitate by freeze- thawing or freeze -drying to get the final product. The product is characterized, with respect to protein composition, by SDS-PAGE and mass-spectroscopy, the content of carotenoids, particularly the xanthophylls violaxanthin, antheraxanthin, and zeaxanthin. The thylakoid preparation has about the same capacity to inhibit pancreatic lipase/colipase activity as thylakoids prepared by standard laboratory methods using sucrose in the medium and centrifugation. In a study with mice, it was found that, when the thylakoids were added to the food over 32 days, they significantly reduced the body weight gain and the percentage body fat. The large scale method described here allows studies on the effect of thylakoids in appetite regulation on experimental animals in a longer lasting time and also on humans.
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| 8. |
- Emek, Sinan Cem, et al.
(författare)
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Pancreatic lipase-colipase binds strongly to the thylakoid membrane surface.
- 2013
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Ingår i: Journal of the Science of Food and Agriculture. - : Wiley. - 1097-0010 .- 0022-5142. ; 93:9, s. 2254-2258
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Isolated thylakoid membranes, i.e. the photosynthetic membranes of green leaves, inhibit the activity of pancreatic lipase and colipase during hydrolysis of fat in vitro. This inhibition has been demonstrated to cause reduced food intake and improved hormonal and lipid profile in vivo. One of the reasons suggested for the inhibiting effect is binding of lipase-colipase to the thylakoid membrane surface. This prompted a study of the binding of lipase and colipase to thylakoids. RESULTS: The results showed that lipase and colipase strongly bind to the thylakoid membrane surface. The dissociation constant was determined at 1.2 × 10(-8) mol L(-1) ; binding decreased after treatment of thylakoids with pepsin/trypsin to 1.0 × 10(-7) and to 0.6 × 10(-7) mol L(-1) after treatment with pancreatic juice. Similarly, delipidation of thylakoids caused a decrease in binding, the dissociation constant being 2.0 × 10(-7) mol L(-1) . CONCLUSION: The binding of pancreatic lipase-colipase to the thylakoid membrane is strong and may explain the inhibition of lipase-colipase activity by thylakoids. After treatment with proteases to mimic intestinal digestion binding is decreased, but is still high enough to explain the observed metabolic effects of thylakoids in vivo. © 2013 Society of Chemical Industry.
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| 9. |
- Emek, Sinan Cem, et al.
(författare)
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Pigments protect the light harvesting proteins of chloroplast thylakoid membranes against digestion by gastrointestinal proteases
- 2011
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Ingår i: Food Hydrocolloids. - : Elsevier BV. - 0268-005X. ; 25:6, s. 1618-1626
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Tidskriftsartikel (refereegranskat)abstract
- Chloroplast thylakoid membranes inhibit pancreatic lipase/colipase activity in vitro and, when included in food, induce satiety signals. As thylakoid membranes themselves are nutrients, containing lipids and proteins, it is of interest to study the digestion of thylakoids by enzymes of the gastrointestinal tract. Thylakoid membranes were treated with pepsin, trypsin, gastric and pancreatic juice at 37 degrees C and the resulting enzymatic breakdown was analyzed by gel electrophoresis, electron microscopy and mass spectroscopy. In all cases, several of the proteins were degraded within half an hour, while the main parts of the pigment-protein complexes were resistant for hours. Oil emulsified thylakoids were more resistant towards the enzymatic breakdown. Electron microscopy demonstrated that, after treatments, the thylakoids still remained in a membrane vesicular form. The capacity of thylakoid membranes to inhibit the lipase/colipase activity was partly reduced in all cases. About 50% of the inhibition capacity remained after treatment with pancreatic juice when the thylakoids were present in an oil emulsion. Delipidated thylakoids and plasma membranes, which lack the photosynthetic pigments, were degraded rapidly by pancreatic juice. Conclusion: The pigments, closely bound to the trans-membrane helices of thylakoid membrane proteins protect these from digestion by pepsin, trypsin, gastric and pancreatic juice. This supports the notion that a substantial inhibition of lipase/colipase takes place during the first 2 h in the intestine resulting in a retardation and prolongation of lipolysis in vivo. (C) 2010 Elsevier Ltd. All rights reserved.
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| 10. |
- Erlanson-Albertsson, Charlotte, et al.
(författare)
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Inhibition of plant growth by the tetrapeptide des-arg enterostatin (VPDP).
- 1996
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Ingår i: Advances in Molecular and Cell Biology.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The effect of the tetrapeptide des-arg -enterostatin (Val-Pro-Asp-Pro) on the growth of muang bean, Vigna rodiate, was studied. At a concentration of 0.2mM in the nutrient solution the peptide reduced the growth significantly. Possible mechanisms underlying the growth inhibition are discussed.
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| 11. |
- Erlanson-Albertsson, Charlotte, et al.
(författare)
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The Use of Green Leaf Membranes to Promote Appetite Control, Suppress Hedonic Hunger and Loose Body Weight.
- 2015
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Ingår i: Plant Foods for Human Nutrition. - : Springer Science and Business Media LLC. - 1573-9104 .- 0921-9668. ; 70:3, s. 281-290
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Tidskriftsartikel (refereegranskat)abstract
- On-going research aims at answering the question, which satiety signal is the most potent or which combination of satiety signals is the most potent to stop eating. There is also an aim at finding certain food items or food additives that could be used to specifically reduce food intake therapeutically. Therapeutic attempts to normalize body weight and glycaemia with single agents alone have generally been disappointing. The success of bariatric surgery illustrates the rationale of using several hormones to treat obesity and type-2-diabetes. We have found that certain components from green leaves, the thylakoids, when given orally have a similar rationale in inducing the release of several gut hormones at the same time. In this way satiety is promoted and hunger suppressed, leading to loss of body weight and body fat. The mechanism is a reduced rate of intestinal lipid hydrolysis, allowing the lipolytic products to reach the distal intestine and release satiety hormones. The thylakoids also regulate glucose uptake in the intestine and influences microbiota composition in the intestine in a prebiotic direction. Using thylakoids is a novel strategy for treatment and prevention of obesity.
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| 12. |
- Erlanson-Albertsson, Charlotte, et al.
(författare)
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Thylakoids Promote Satiety in Healthy Humans. Metabolic Effects and Mechanisms
- 2012
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Ingår i: ACS Symposium Series. - 0097-6156. ; 1093, s. 521-531
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Konferensbidrag (refereegranskat)abstract
- Thylakoids are the photosynthetic membranes of the chloroplasts in green leaves. Thylakoids have been found to promote satiety when added to food, both in animal experimental models and in human. The thylakoids act through inhibition of lipase-colipase catalysed hydrolysis of triacylglycerol, which is the main dietary fat component. The mechanism for inhibition is either a binding of thylakoids to lipase-colipase, which thereby prevents to act as a lipolytic enzyme complex or binding of thylakoids to the triacylglycerol droplet, thereby hindering the access of lipase-colipase to its substrate. Thylakoids consist of proteins and lipids in a membrane structure containing various protein-bound pigments. The thylakoid membranes are fairly resistant to gastrointestinal breakdown, which may be an important property to explain the satiety promoting effect. Satiety is promoted through the release of cholecystokinin, a gastrointestinal hormone that causes an inhibition of gastric emptying and stimulation of satiety mechanism in the brain. The hunger hormone ghrelin is suppressed as well as insulin. In human short-term experiments thylakoids added to food promote satiety signalling. In long-term a reduced body fat mass was observed.
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| 13. |
- Fokkema, Marieke L., et al.
(författare)
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Outcome after percutaneous coronary intervention for different indications : long-term results from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
- 2016
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Ingår i: EuroIntervention. - Toulouse, France : Europa Edition. - 1774-024X .- 1969-6213. ; 12:3, s. 303-311
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to evaluate clinical outcome for different indications for PCI in an unselected, nationwide PCI population at short- and long-term follow-up.Methods and results: We evaluated clinical outcome up to six years after PCI in all patients undergoing a PCI procedure for different indications in Sweden between 2006 and 2010. A total of 70,479 patients were treated for stable coronary artery disease (CAD) (21.0%), unstable angina (11.0%), non-ST-elevation myocardial infarction (NSTEMI) (36.6%) and ST-elevation myocardial infarction (STEMI) (31.4%). Mortality was higher in STEMI patients at one year after PCI (9.6%) compared to NSTEMI (4.7%), unstable angina (2.2%) and stable CAD (2.0%). At one year after PCI until the end of follow-up, the adjusted mortality risk (one to six years after PCI) and the risk of myocardial infarction were comparable between NSTEMI and STEMI patients and lower in patients with unstable angina and stable CAD. The adjusted risk of stent thrombosis and heart failure was highest in STEMI patients.Conclusions: The risk of short-term mortality, heart failure and stent thrombosis is highest for STEMI patients after PCI. Therapies to reduce stent thrombosis and heart failure appear to be most important in decreasing mortality in patients with STEMI or NSTEMI undergoing PCI.
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| 14. |
- Köhnke, Rickard, et al.
(författare)
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Thylakoids promote release of the satiety hormone cholecystokinin while reducing insulin in healthy humans.
- 2009
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 44:6, s. 712-719
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The effects of a promising new appetite suppressor named "thylakoids" (membrane proteins derived from spinach leaves) were examined in a single meal in man. Thylakoids inhibit the lipase/colipase hydrolysis of triacylglycerols in vitro and suppress food intake, decrease body-weight gain and raise the satiety hormone cholecystokinin (CCK) in rats, but their effects in man remain unclear. The aim of this study was to investigate whether thylakoids, when added to a test meal, affect appetite regulation and blood parameters in healthy individuals. Material and methods. In an intervention crossover study, healthy individuals of normal weight (n=11) were offered a high-fat meal with and without the addition of thylakoids. Blood samples were taken 0 (prior to meal), 30, 60, 120, 180, 240, 300 and 360 min after the start of the meal. Blood samples were analysed for satiety and hunger hormones (CCK, leptin and ghrelin), insulin and blood metabolites (glucose and free fatty acids). Results. The CCK level increased, in particular between the 120 min time-point and onwards, the ghrelin level was reduced at 120 min and leptin level increased at 360 min after intake of the thylakoid-enriched meal. The insulin level was reduced, whereas glucose concentrations were unchanged. Free fatty acids were reduced between time-point 120 min and onwards after the thylakoid meal. Conclusions. The addition of thylakoids to energy-dense food promotes satiety signals and reduces insulin response during a single meal in man.
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| 15. |
- Köhnke, Rickard, et al.
(författare)
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Thylakoids suppress appetite by increasing cholecystokinin resulting in lower food intake and body weight in high-fat fed mice.
- 2009
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Ingår i: Phytotherapy Research. - : Wiley. - 1099-1573 .- 0951-418X. ; 23, s. 1778-1783
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Tidskriftsartikel (refereegranskat)abstract
- Thylakoids are membranes isolated from plant chloroplasts which have previously been shown to inhibit pancreatic lipase/colipase catalysed hydrolysis of fat in vitro and induce short-term satiety in vivo. The purpose of the present study was to examine if dietary supplementation of thylakoids could affect food intake and body weight during long-term feeding in mice. Female apolipoprotein E-deficient mice were fed a high-fat diet containing 41% of fat by energy with and without thylakoids for 100 days. Mice fed the thylakoid-enriched diet had suppressed food intake, body weight gain and body fat compared with the high-fat fed control mice. Reduced serum glucose, serum triglyceride and serum free fatty acid levels were found in the thylakoid-treated animals. The satiety hormone cholecystokinin was elevated, suggesting this hormone mediates satiety. Leptin levels were reduced, reflecting a decreased fat mass. There was no sign of desensitization in the animals treated with thylakoids. The results suggest that thylakoids are useful to suppress appetite and body weight gain when supplemented to a high-fat food during long-term feeding. Copyright (c) 2009 John Wiley & Sons, Ltd.
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| 16. |
- Leidermark, Erik, 1981, et al.
(författare)
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Estimating the risk for secondary cancer following targeted alpha therapy with astatine-211 intraperitoneal radioimmunotherapy.
- 2022
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Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - : Society of Nuclear Medicine. - 1535-5667. ; 64:1, s. 165-172
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Tidskriftsartikel (refereegranskat)abstract
- Intraperitoneal 211At-based targeted alpha therapy (TAT) may hold most promise as an adjuvant therapy following surgery and chemotherapy in epithelial ovarian cancer to eradicate any remaining undetectable disease. This implies it will also be delivered to patients possibly already cured by the primary treatment. An estimate of long-term risks is therefore sought whether to justify the treatment. Methods: Baseline data for risk estimates of alpha-particle irradiation were collected from published studies on excess cancer induction and mortality for subjects exposed to either 224Ra treatments or Thorotrast contrast agent (25% ThO2 colloid, containing 232Th). Organ dosimetry for 224Ra and Thorotrast irradiation were taken from the literature. These organ-specific risks were then applied for our previously reported dosimetry for intraperitoneal (i.p.) 211At-TAT patients. Results: Risk could be estimated for 10 different organ or organ groups. The calculated excess relative risk per Gray (ERR/Gy) could be sorted into two groups. In the lower ERR/Gy group, up to approx. 5, were: Trachea, bronchus and lung 0.52 (CI 95% 0.21-0.82), Stomach 1.4 (CI 95% -5.0-7.9), Lymphoid and hematopoietic system 2.17 (CI 95% 1.7-2.7), Bone and articular cartilage 2.6 (CI 95% 2.0-3.3), Breast 3.45 (CI 95% -10-17) and Colon 4.5 (CI 95% -3.5-13). In the higher ERR/Gy group, ranging from approx. 10 to 15 were: Urinary bladder 10.1 (CI 95% 1.4-23), Liver 14.2 (CI 95% 13-16), Kidney 14.9 (CI 95% 3.9-26) and Lip, oral cavity and pharynx 15.20 (CI 95% 2.73-27.63). Applying a typical candidate patient (female, age 65 years) and correcting for reference population mortality rate, a total estimated excess mortality of an i.p. 211At-mAb treatment amounted to 1.13 per 100 treated. More than half of this excess originated from urinary bladder and kidney, 0.29 and 0.34 respectively. Depending on various adjustments in calculation and assumptions on competing risks excess mortality could range from 0.11 - 1.84 per 100 treated. Conclusion: Published epidemiological data on life-long detriment following alpha-particle irradiation and its dosimetry allowed calculations to estimate the risk for secondary cancer following 211At-based i.p. TAT. Measures to reduce dose to the urinary organs may further decrease the estimated relative low risk for secondary cancer from 211At-mAb based i.p. TAT.
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| 17. |
- Libungan, Berglind, et al.
(författare)
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Out-of-hospital cardiac arrest in the elderly : A large-scale population-based study.
- 2015
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 94
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is little information on elderly people who suffer from out-of-hospital cardiac arrest (OHCA).AIM: To determine 30-day mortality and neurological outcome in elderly patients with OHCA.METHODS: OHCA patients ≥ 70 years of age who were registered in the Swedish Cardiopulmonary Resuscitation Register between 1990 and 2013 were included and divided into three age categories (70-79, 80-89, and ≥ 90 years). Multiple logistic regression analyses were performed to identify independent predictors of 30-day survival.RESULTS: Altogether, 36,605 cases were included in the study. Thirty-day survival was 6.7% in patients aged 70-79 years, 4.4% in patients aged 80-89 years, and 2.4% in those over 90 years. For patients with witnessed OHCA of cardiac aetiology found in a shockable rhythm, survival was higher: 20%, 15%, and 11%, respectively. In 30-day survivors, the distribution according to the cerebral performance categories (CPC) score at discharge from hospital was similar in the three age groups. In multivariate analysis, in patients over 70 years of age, the following factors were associated with increased chance of 30-day survival: younger age, OHCA outside the home, witnessed OHCA, CPR before arrival of EMS, shockable first-recorded rhythm, and short emergency response time.CONCLUSIONS: Advanced age is an independent predictor of mortality in OHCA patients over 70 years of age. However, even in patients above 90 years of age, defined subsets with a survival rate of more than 10% exist. In survivors, the neurological outcome remains similar regardless of age.
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| 18. |
- Montelius, Caroline, et al.
(författare)
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Chloroplast thylakoids reduce glucose uptake and decrease intestinal macromolecular permeability.
- 2011
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 106:6, s. 836-844
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Tidskriftsartikel (refereegranskat)abstract
- Thylakoid membranes, derived from chloroplasts, have previously been shown to retard fat digestion and lower blood glucose levels after oral intake. The purpose of the present study was to investigate the effect of thylakoid membranes on the passage of methyl-glucose, dextran and ovalbumin over rat intestine in vitro using Ussing chambers. The results show that thylakoids retard the passage of each of the test molecules in a dose-dependent way. The thylakoids appear to be attached on the mucosal surface and a mechanism is suggested that the thylakoids delay the passage of the test molecules by sterical hindrance. The present results indicate that thylakoid membranes may be useful both to control intestinal absorption of glucose and to enhance the barrier function of the intestine.
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| 19. |
- Montelius, Caroline, et al.
(författare)
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Feeding spinach thylakoids to rats modulates the gut microbiota, decreases food intake and affects the insulin response
- 2013
-
Ingår i: Journal of Nutritional Science. - : Cambridge University Press (CUP). - 2048-6790. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Thylakoid membranes derived from green leaf chloroplasts affect appetite-regulating hormones, suppress food intake, reduce blood lipids and lead to a decreased body weight in animals and human subjects. Thylakoids also decrease the intestinal in vitro uptake of methyl-glucose in the rat. The aim of this study was to investigate the effect of dietary thylakoids on the gut microbiota composition, mainly the taxa of lactobacilli and bifidobacteria, in rats fed either a thylakoid-enriched diet or a control diet for 10 d. At the same time, a glucose-tolerance test in the same rats was also performed. Food intake was significantly decreased in the thylakoid-fed rats compared with the control-fed rats over the 10-d study. An oral glucose tolerance test after 10 d of thylakoid- or control-food intake resulted in significantly reduced plasma insulin levels in the thylakoid-fed rats compared with the control-fed rats, while no difference was observed for blood glucose levels. Analysis of gut bacteria showed a significant increase of lactobacilli on the ileal mucosa, specifically Lactobacillus reuteri, in the rats fed the thylakoid diet compared with rats fed the control diet, while faecal lactobacilli decreased. No difference in bifidobacteria between the thylakoid and control groups was found. Analyses with terminal restriction fragment length polymorphism and principal component analysis of faeces demonstrated different microbial populations in the thylakoid- and control-fed animals. These findings indicate that thylakoids modulate the gut microbial composition, which might be important for the regulation of body weight and energy metabolism.
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| 20. |
- Nordenskjöld, Anna, 1969, et al.
(författare)
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Breast cancer survival trends in different stages and age groups - a population-based study 1989-2013
- 2019
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Ingår i: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 58:1, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- Background: During the recent decades, breast cancer survival has gradually improved but there is limited knowledge on the improvement in population-based studies of patients diagnosed with different stages of the disease and in different age groups.Patients and methods: In two Swedish health care regions a total of 42,220 female breast cancer patients below 90years of age were diagnosed between 1989 and 2013. They were treated and followed according to national and regional guidelines and formed a population-based cohort.Results: Using patients diagnosed in 1989-1993 as a reference to the relative risk, 5-year mortality decreased with 49% for patients diagnosed at the end of the observation period (CI 95% 45-58). The mortality tended to decrease for patients with all stages of breast cancer and test for trend resulted in a statistically significant improvement over time in 5-year relative survival in stage III and IV and in 10-year survival in stage I and III. For each operable stage of disease, patients aged below 40years or more than 70years when diagnosed tended to have less favorable survival than patients diagnosed between 40-69years of age. Test for trend resulted in statistically significant improvements over time for patients diagnosed at ages below 40, 40-54 and 54-69, but less marked improvements for patients older than 70 when diagnosed.Conclusions: During the period 1989-2013 the relative risk of 5-year mortality decreased with 49%. Improvements were seen in all age groups but were unevenly distributed between stages and age groups pointing to the need for further improvements for younger and elderly patients.
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| 21. |
- Nordenskjöld, Anna, 1969, et al.
(författare)
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No clear effect of postoperative radiotherapy on survival of breast cancer patients with one to three positive nodes: a population-based study
- 2015
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Ingår i: Annals of Oncology. - : Oxford University Press (OUP): Policy B - Oxford Open Option F. - 0923-7534 .- 1569-8041. ; 26:6, s. 1149-1154
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Tidskriftsartikel (refereegranskat)abstract
- Background: In published radiotherapy trials, the failure rate in the control arm among patients with one to three positive nodes is high compared with that seen with modern adjuvant treatments. Therefore, the generalizability of the results has been questioned. The aim of the present study was to compare relative survival in breast cancer patients between two Swedish regions with screening mammography programs and adjuvant treatment guidelines similar with the exception of the indication of radiotherapy for patients with one to three positive nodes. Patients and methods: Between 1989 and 2006, breast cancer patients were managed very similarly in the west and southeast regions, except for indication for postoperative radiotherapy. In patients with one to three positive nodes, post-mastectomy radiotherapy was generally given in the southeast region (89% of all cases) and generally not given in the west region (15% of all cases). For patients with one to three positive nodes who underwent breast-conserving surgery, patients in the west region had breast radiotherapy only, while patients in the southeast region had both breast and lymph nodes irradiated. Results: The 10-year relative survival for patients with one to three positive lymph nodes was 78% in the west region and 77% in the southeast region (P = 0.12). Separate analyses depending on type of surgery, as well as number of examined nodes, also revealed similar relative survival. Conclusion: Locoregional postoperative radiotherapy has well-known side-effects, but in this population-based study, there was little or no influence of this type of radiotherapy on survival when one to three lymph nodes were involved.
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| 22. |
- Omerovic, Elmir, 1968, et al.
(författare)
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Levosimendan neither improves nor worsens mortality in patients with cardiogenic shock due to ST-elevation myocardial infarction.
- 2010
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Ingår i: Vascular health and risk management. - 1178-2048. ; 7:6, s. 657-663
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to evaluate the effect of levosimendan on mortality in cardiogenic shock (CS) after ST elevation myocardial infarction (STEMI). METHODS AND RESULTS: Data were obtained prospectively from the SCAAR (Swedish Coronary Angiography and Angioplasty Register) and the RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) about 94 consecutive patients with CS due to STEMI. Patients were classified into levosimendan-mandatory and levosimendan-contraindicated cohorts. Inotropic support with levosimendan was mandatory in all patients between January 2004 and December 2005 (n = 46). After the SURVIVE and REVIVE II studies were presented, levosimendan was considered contraindicated and was not used in consecutive patients between December 2005 and December 2006 (n = 48). The cohorts were similar with respect to pre-treatment characteristics and concomitant medications. There was no difference in the incidence of new-onset atrial fibrillation, in-hospital cardiac arrest and length of stay at the coronary care unit. There was no difference in adjusted mortality at 30 days and at one year. CONCLUSION: The use of levosimendan neither improves nor worsens mortality in patients with CS due to STEMI. Well-designed randomized clinical trials are needed to define the role of inotropic therapy in the treatment of CS.
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| 23. |
- Rayner, Marilyn, et al.
(författare)
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A novel emulsifier from spinach with appetite regulation abilities
- 2011
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Ingår i: Procedia Food Science. - : Elsevier BV. - 2211-601X. ; 1, s. 1431-1438
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Tidskriftsartikel (refereegranskat)abstract
- Chloroplast thylakoid membranes inhibit pancreatic lipase/colipase activity in vitro and, when included in food, induce satiety signals. This effect is due to their ability to reduce the rate of lipolysis through the inhibition of the lipase-colipase complex. They have a strong affinity to oil which both prevents the lipolytic enzymes from in close contact with its substrate and at the same time protects the thylakoids form proteolytic enzymes present in gastric juices form digesting the thylakoids as quickly. This affinity also imparts thylakoids interesting emulsification properties. The objective of this study was to characterize thylakoids’ ability to stabilize oil-in-water emulsions, and to study their interfacial properties in light of their capacity to inhibit pancreatic lipase-co lipase activity in vitro. As lipolysis is an inherently interfacial process it is important to quantify their interfacial properties and to maximize the oil-water interfacial area covered by the thylakoids in future food formulations. Thylakoids isolated from spinach were used for emulsification studies using a lab-scale high shear homogenizer. The oil-in-water emulsions produced had varying amounts of thylakoids and resulting emulsions were characterized by creaming phase volume, microscopy and light scattering to determine microstructure and droplet size distributions as well as surface load. Electron micrographs showed thylakoids adsorbed as loosely bunched vesicles on the drop surfaces approximately 1 micron in size, and were found to effectively stabilize the oil water interface, but with large droplet size (20 to 200 micron range) and relatively high surface loads (2 to 10 mg/m2).
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| 24. |
- Rayner, Marilyn, et al.
(författare)
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Chloroplast thylakoid membrane-stabilised emulsions.
- 2011
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Ingår i: Journal of the Science of Food and Agriculture. - : Wiley. - 1097-0010 .- 0022-5142. ; 91:2, s. 315-321
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Thylakoid-stabilised emulsions have been reported to possess satiety-promoting effects and inhibit pancreatic lipase-colipase activity in vitro, which prompted the investigation of their interfacial properties.RESULTS: Thylakoid membranes isolated from spinach were used as an emulsifier/stabiliser in oil (triglyceride)-in-water emulsions. Emulsions were characterised with respect to droplet size, interfacial tension, creaming, surface load and electron microscopy. The effects of pH and thylakoid concentration were also considered. Droplet size decreased with increasing thylakoid concentration, reaching a plateau around 15 microm beyond concentrations of 2 mg protein mL(-1) oil. The resulting emulsions were stable against coalescence but were subject to creaming. The surface pressure (air/water interface) of the thylakoid isolate was 44 mN m(-1) and the surface load 13 mg m(-2) at 10 mg protein mL(-1) oil. Electron micrographs showed thylakoids adsorbed as bunched vesicles on the drop surfaces. The stabilisation mechanism can be described as a combined effect of surface-active molecules, mainly membrane proteins but also membrane lipids, exposed on surfaces of thylakoid membrane vesicles adsorbed as particles.CONCLUSION: Thylakoid membranes effectively stabilise oil-in-water emulsions, which should facilitate their incorporation in food with satiety-promoting effects. To the authors' knowledge, this is the first study on the emulsifying properties of an isolated biological membrane as a functional ingredient.
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| 25. |
- Redfors, Björn, et al.
(författare)
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Prognosis is similar for patients who undergo primary PCI during regular-hours and off-hours: A report from SCAAR.
- 2018
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Ingår i: Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions. - : Wiley. - 1522-726X. ; 91:7, s. 1240-1249
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Tidskriftsartikel (refereegranskat)abstract
- Timely percutaneous coronary intervention (PCI) improves prognosis in ST-elevation myocardial infarction (STEMI). However, recent reports indicate that patients with STEMI who present during non-regular working hours (off-hours) have a worse prognosis. The aim of this study was to compare outcome between patients with STEMI who underwent primary PCI during off-hours and regular hours.We retrieved data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for all patients who underwent primary PCI in Region Västra Götaland due to STEMI between January 2004 and May 2013. We modeled unadjusted and adjusted Cox proportional-hazards regression and logistic regression models for the outcomes death, cardiogenic shock, stent thrombosis and in-stent restenosis. A propensity score-adjusted Cox proportional-hazards model, which adjusted for traditional cardiovascular risk factors was predefined as the primary statistical model. Death at any time during the study period was pre-specified as primary end-point.During the study period 4.611 (65%) patients underwent primary PCI due to STEMI during off-hours and 2,525 (35%) during regular hours. The risk of dying was similar among the groups for the primary endpoint death at any time during the study period (HR 1.00, 95% CI 0.89-1.12, P=0.991) and for secondary end-point death within 30 days (HR 1.03; 95% CI 0.85-1.25, P=0.735). The risks of developing cardiogenic shock, stent thrombosis, or in-stent restenosis were similar between the groups.In our region, short- and long-term prognosis for patients with STEMI who undergo primary PCI is similar for patients presenting during off-hours and regular hours.
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| 26. |
- Östbring, Karolina, et al.
(författare)
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Heat-induced aggregation of thylakoid membranes affect their interfacial properties.
- 2015
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Ingår i: Food & Function. - : Royal Society of Chemistry (RSC). - 2042-6496 .- 2042-650X. ; 6:4, s. 1310-1318
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Tidskriftsartikel (refereegranskat)abstract
- Many of our most popular lipid containing foods are in emulsion form. These foods are often highly palatable with high caloric density, that subsequently increases the risk of overconsumption and possibly lead to obesity. Regulating the lipid bioavailability of high-fat foods is one approach to prevent overconsumption. Thylakoids, the chloroplast membrane, creates a barrier around lipid droplets, which prolong lipolysis and increase satiety as demonstrated both in animal and human studies. However, a reduced lipase inhibiting capacity has been reported after heat treatment but the mechanism has not yet been fully established. The aim of this study was to investigate thylakoids' emulsifying properties post heat-treatment and possible links to alterations in lipase inhibiting capacity and chlorophyll degradation. Heat-treatment of thylakoids at either 60 °C, 75 °C or 90 °C for time interval ranging from 15 s to 4 min reduced ability to stabilise emulsions, having increased lipid droplets sizes, reduced emulsification capacity, and elevated surface load as consequence. Emulsifying properties were also found to display a linear relationship to both chlorophyll and lipase inhibiting capacity. The correlations support the hypothesis that heat-treatment induce chlorophyll degradation which promote aggregation within proteins inside the thylakoid membrane known to play a decisive role in interfacial processes. Therefore, heat-treatment of thylakoids affects both chlorophyll content, lipase inhibiting capacity and ability to stabilise the oil-water interface. Since the thylakoid's appetite reducing properties are a surface-related phenomenon, the results are useful to optimize the effect of thylakoids as an appetite reducing agent.
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| 27. |
- Östbring, Karolina, et al.
(författare)
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The effect of heat treatment of thylakoids on their ability to inhibit in vitro lipase/co-lipase activity.
- 2014
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Ingår i: Food & Function. - : Royal Society of Chemistry (RSC). - 2042-6496 .- 2042-650X. ; 5:9, s. 2157-2165
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Tidskriftsartikel (refereegranskat)abstract
- Thylakoids has been shown to prolong lipolysis by the inhibition of lipase/co-lipase, which makes thylakoids suitable as a functional food ingredient with satiating properties. The components of thylakoids that provide its function as a lipolysis modulator are primarily photosystems I and II, which are structurally stabilised by chlorophyll. However, chlorophyll is known to be heat sensitive yet the enzymatic inhibiting capacity after heat treatment has not been previously studied. It was hypothesised that the retained function of thylakoids after heat treatment could be correlated to the degree of degradation. Heat treatment at either 60 °C, 75 °C or 90 °C for time interval ranging from 15 s to 120 min induced a color shift from bright green to olive brown which was attributed to degradation. The ability of heat-treated thylakoids to inhibit lipolysis in vitro was also reduced. A correlation between chlorophyll a degradation and the enzymatic inhibiting capacity could be established which opens possibilities to use a spectrophotometric method to quantify the ability of thylakoids to inhibit lipase/co-lipase in a more rapid and cost effective way to complement the pH-stat method used today. With the degradation pattern investigated, it is then possible to design a thermal treatment process to ensure a microbiological safe appetite-reducing product and at the same time minimize the loss of functionality.
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| 28. |
- Adingupu, D. D., et al.
(författare)
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Radial artery intima-media thickness regresses after secondary prevention interventions in patients' post-acute coronary syndrome and is associated with cardiac and kidney biomarkers
- 2017
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:32, s. 53419-53431
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Tidskriftsartikel (refereegranskat)abstract
- Background: Radial artery intima-media thickness (rIMT) measured by ultra-high-resolution ultrasound is associated with increased cardiovascular risk and predicts outcomes. We performed non-invasive high-resolution ultrasound of the radial artery to investigate vascular changes in subjects presenting with acute coronary syndrome (ACS) and who had undergone percutaneous coronary intervention (PCI). Purpose: In the present work, we aimed to follow rIMT change over time post-acute coronary syndrome as a tool to monitor potential response to intensified medical therapy. Methods: We examined 256 subjects who underwent PCI due to ACS and healthy controls (n= 39) and we measured a number of biomarkers, which are known to be associated with cardiovascular disease. Images of radial artery were acquired bilaterally in the longitudinal view using a 50 MHz transducer (Vevo 2100 VisualSonics, Inc, Toronto, Ontario, Canada). Carotid IMT (cIMT) and rIMT were measured at <1 month after index PCI followed by a repeated measurement of rIMT at 4 months from the ACS in a sub-set (n= 117). Results: rIMT measured within 1 month post ACS was significantly higher than rIMT after 4 months from ACS, (p < 0.0001), mean +/- SD (rIMT right 0.35 +/- 0.08; rIMT left 0.37 +/- 0.08) vs. (rIMT right 0.29 +/- 0.08; rIMT left 0.31 +/- 0.09) respectively. There was no statistically significant change in cIMT. In healthy controls there were no changes in rIMT or cIMT overtime. High levels of CX3CL1 and myeloperoxidase measured within one month post ACS are associated with increase of rIMT, r=0.38 (p< 0.0001) and r=0.41 (p< 0.0001) respectively. Conclusions: rIMT seem to decrease systemically after ACS and is accompanied with corresponding biomarker change. The cause and clinical implications of the observed decrement in rIMT after ACS need further studies.
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| 29. |
- Albertsson, Per, 1964, et al.
(författare)
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Astatine-211 based radionuclide therapy: Current clinical trial landscape
- 2023
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Astatine-211 (At-211) has physical properties that make it one of the top candidates for use as a radiation source for alpha particle-based radionuclide therapy, also referred to as targeted alpha therapy (TAT). Here, we summarize the main results of the completed clinical trials, further describe ongoing trials, and discuss future prospects.
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| 30. |
- Albertsson, Per, 1964, et al.
(författare)
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Chemotherapy and antiangiogenesis: drug-specific effects on microvessel sprouting
- 2003
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Ingår i: Apmis. - 0903-4641. ; 111:11, s. 995-1003
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Tidskriftsartikel (refereegranskat)abstract
- Tumors are angiogenesis dependent. Some chemotherapeutics have been shown to be able to suppress angiogenesis and thus tumor growth in vivo at low, well-tolerated doses. Not much is known about the angiogenesis-modulating effects of chemotherapeutics in vivo, however. Microvessel sprouting is inherent to angiogenesis. Using the rat mesentery assay, we studied the effect of cyclophosphamide, doxorubicin and paclitaxel at a low, atoxic dose on the number of sprouts per unit tissue volume (No. SP) and their length (Le. SP) at the edge of the expanding network in VEGF165-mediated angiogenesis. A single dose of each cytotoxic drug was administered i.v. 7 days before the animals were sacrificed. Cyclophosphamide significantly lengthened the shortest Le. SP and shortened the longest Le. SP, doxorubicin did not significantly affect Le. SP, whereas paclitaxel significantly shortened both the shortest and the longest Le. SP. No correlation was found between the present results and the distinctly drug-specific results of microvessel segment number and length analyzed within central parts of the same expanding network. To our knowledge, this is the first quantitative report on the effect of chemotherapy on angiogenesis sprouting in vivo. Collectively, the data suggest that cyclophosphamide, doxorubicin and paclitaxel at a non-toxic dose primarily target different intrinsic components of the angiogenic cascade, leading to distinctly drug-specific effects.
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| 31. |
- Albertsson, Per, 1964, et al.
(författare)
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Differential locomotion of long- and short-term IL-2-activated murine natural killer cells in a model matrix environment.
- 2007
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Ingår i: Scandinavian journal of immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 66:4, s. 402-9
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Tidskriftsartikel (refereegranskat)abstract
- Tumour infiltration by activated natural killer (A-NK) cells is a pre-requisite for tumour eradication by adoptive NK cell transfer. Extravasated A-NK cells do not always succeed in reaching the crucial target cell conjugation. Therefore, we wished to study A-NK cell locomotion and interactions with melanoma cells in a matrix environment (Matrigel) by electron, confocal and fluorescence microscopy. Two distinct patterns of A-NK cell-mediated matrix disintegration were revealed during incubation of tumour cells and A-NK cells in Matrigel: (1) A-NK cells pre-cultured for 5 days altered the homogeneous texture of the Matrigel, an initial microporous appearance became a loose filamentous meshwork by 24 h. Matrix degrading protease inhibitors could not fully prevent this, but could delay the process; and (2) A-NK cells pre-cultured for 6 days or more, instead formed large excavations in the Matrigel leaving the remaining matrix less affected compared to the effects by the younger A-NK cells. By histochemical staining with Cupromeronic Blue, the excavations were shown to contain proteoglycan material. Protease inhibitors had no discernable effect on the development of the excavations. The conspicuous capacity of A-NK cells to disintegrate extracellular matrix and the formation of large excavations seems only partially to depend on matrix-degrading proteases. Formation of extracellular proteoglycan material is suggested to facilitate A-NK cell locomotion within a matrix environment.
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| 32. |
- Albertsson, Per, 1964, et al.
(författare)
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Dose effects of continuous vinblastine chemotherapy on mammalian angiogenesis mediated by VEGF-A.
- 2008
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 47:2, s. 293-300
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Tidskriftsartikel (refereegranskat)abstract
- Low-dose continuous or metronomic chemotherapy with several agents can exert significant antiangiogenic effects, as shown in preclinical studies. Therapy of this kind is generally well tolerated compared with conventional chemotherapy with high, temporally spaced out bolus doses. A critical point emerges when the effects on angiogenesis of low-toxic metronomic doses of chemotherapeutics in preclinical studies are to be transferred to clinical protocols, as there is a risk that a virtually non-toxic dose might also be ineffective; clearly, dose-effect data are important. We therefore sought to investigate whether a dose-dependent response exists in metronomic vinblastine chemotherapy. The surrogate tumor-free rat mesentery model, allowing the study of antiangiogenic effects per se, was used. Following systemically administered metronomic chemotherapy, it closely reflects the indirectly assessed antiangiogenic and growth-retarding effects in a syngenic cancer model. VEGF-A, which is a central proangiogenic factor in most tumors, was administered i.p. to induce angiogenesis in the mesenteric test tissue and, using morphometry, the angiogenesis-modulating effects of vinblastine were assessed in terms of objective quantitative variables. We report that continuous vinblastine treatment with an apparently non-toxic dose (1.0 mg/kg/week or 0.143 mg/kg/day) for 10 days, and a dose that substantially inhibited the physiologic body-weight gain (2.0 mg/kg/week or 0.286 mg/kg/day) for 6 days, demonstrates a dose-response relationship; the high dose significantly suppresses angiogenesis. To our knowledge, no previous study has reported on a dose-dependent antiangiogenic effect by continuous or metronomic vinblastine treatment in a mammalian in vivo model.
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| 33. |
- Albertsson, Per, 1964, et al.
(författare)
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Low-dosage metronomic chemotherapy and angiogenesis: topoisomerase inhibitors irinotecan and mitoxantrone stimulate VEGF-A-mediated angiogenesis.
- 2012
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 120:2, s. 147-56
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Tidskriftsartikel (refereegranskat)abstract
- Metronomic chemotherapy with cytotoxic agents has been shown to inhibit angiogenesis and, consequently, tumor growth by targeting vascular endothelial cells (ECs). In these regimens, anti-tumor activities additional to anti-angiogenesis may operate. Moreover, chemotherapy typically generates reactive oxygen species in targeted ECs, which can affect angiogenesis. The aim of the present study was to assess the systemic effect of low-dosage metronomic treatment with either irinotecan or mitoxantrone on angiogenesis induced by VEGF-A. Angiogenesis was induced in normal adult rat mesentery by intraperitoneal injection of a low dosage of VEGF-A. Thereafter, irinotecan and mitoxantrone were infused separately continuously at minimally toxic dosages for 14 consecutive days via a subcutaneous osmotic minipump. Angiogenesis was assessed in terms of objective and quantitative variables using morphologic and computerized image analyses. Irinotecan or mitoxantrone significantly stimulated angiogenesis, with ironotecan increasing angiogenesis by 104%, when compared with the vehicle-treated animals. Low-dosage metronomic chemotherapy with irinotecan or mitoxantrone stimulates angiogenesis in the normal mesentery of rats, probably by inducing low-level oxidative stress in the targeted ECs. Whether or not this pertains to tumor angiogenesis may be difficult to confirm, as several anti-tumor modes may operate during low-dosage metronomic chemotherapy.
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| 34. |
- Albertsson, Per, 1964, et al.
(författare)
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Low-dose continuous 5-fluorouracil infusion stimulates VEGF-A-mediated angiogenesis.
- 2009
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:3, s. 418-25
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tumor growth is angiogenesis-dependent. Animal studies have demonstrated that frequent administration of chemotherapeutics may have marked antiangiogenic effects and improved antitumor effects, with less severe toxic side-effects than intermittent maximum tolerated dose chemotherapy. Currently, research focused on low-dose antiangiogenic chemotherapy is increasing. We have recently reported that certain chemotherapeutics, including 5-fluorouracil (5-FU), may in fact stimulate angiogenesis in the tumor-free rat mesenteric window assay. The aim of the present study was to extend the investigation of the angiogenesis-modulating effects of 5-FU by prolonging the continuous infusion treatment time. METHOD: Angiogenesis was induced in the mesenteric test tissue in adult male Sprague-Dawley rats by i.p. injection of VEGF-A, which is a key angiogenic factor in most tumors. During the subsequent angiogenesis, 5-FU was delivered continuously for 14 days by an osmotic pump implanted subcutaneously. The angiogenic response was analyzed by morphometry in the mesenteric windows. RESULTS: The 14-days continuous infusion of 5-FU significantly stimulated angiogenesis. Thus the possibility that the previously reported surprising proangiogenic effect of 5-FU reflected an insufficiently long treatment period can be ruled out. CONCLUSION: The finding that continuously infused 5-FU is able to stimulate angiogenesis in the present rat model of angiogenesis warrants investigation of the mechanisms behind this unexpected finding. It may further have implications for the choice of antiangiogenic chemotherapeutic schedule used for cancer patients.
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| 35. |
- Albertsson, Per, 1964
(författare)
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Matrix metalloproteinases in natural killer cells. Expression of MMPs, IL-2 activation and killer cell interactions with Matrigel® and model tumours
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: IL-2 activated natural killer (A-NK) cells can recognize malignant cells and exert tumouricidal activities by multiple mechanisms that require close contact with the target cells. Upon adoptive transfer, some A-NK cells accumulate in tumours by migrating from the vascular bed to a position inside the malignant tissue, forming close contacts with target cells. This process requires that naturally occurring barriers are passed, i.e. the endothelial lining with the underlying basement membrane and the adjacent extracellular matrix, ECM. Thus, tumour infiltration by A-NK cells is believed to depend in part on proteolytic matrix degradation, in analogy with malignant cell invasion during formation of metastasis. This focuses on expression, release, and possible functions of ECM degrading proteases in NK cells. Specific aims: to explore the repertoire of matrix metalloproteinases (MMPs) in NK/A-NK cells of various species; to examine whether MMPs are utilised in the process of basement membrane transmigration; to describe the morphology of A-NK cell infiltration in ECM and in model tumours as related to proteolytic mechanismsMaterials & Methods: Gelatin zymography, Western blotting and reverse transcriptase (RT-) PCR were used to detect and identify the various MMPs in NK/A-NK cell membranes and culture supernatants. Transmigration assays using Matrigel (reconstituted basement membrane ECM) covered invasion-chambers. A-NK-to-matrix and A-NK-to-tumour cell interactions were investigated by means of light and fluorescence microscopy, and electron microscopy. Model B16 melanoma tumours formed in vitro and growing intraperitoneally were used.Results: Expression and release of multiple MMPs were demonstrated in NK cells from different species. In rat MMP-2 and MMP-9 were found, in mice MMP-2, MMP-9, MMP-11, MMP-13, MT1-MMP, MT2-MMP and the specific inhibitors TIMP-1 and TIMP-2. In human NK cells MMP-2, MMP-8, MMP-9 and MT1-MMP as well as TIMP-1 were detected. A-NK cell transmigration through a basement membrane material was inhibited to about 50% (rat cells) or 90% (murine cells) by the MMP inhibitor batimastat (BB94). Human A-NK cell migrated across the membranes in a seemingly IL-2-dependent manner. Microscopy demonstrated that infiltrating A-NK cells disintegrate B16 tumour cell aggregates in vitro, which was not related to cytolysis. Further, an A-NK cell age-dependent alteration of Matrigel was detected. Short-term cultured cells caused a general digestion of the matrix material which contrasted to the effect of older A-NK cells that created large excavations around the cells with little alteration on the remaining Matrigel. A-NK cells infiltrated, but did not disintegrate, intraperitoneal tumours.Conclusions: NK/A-NK cells express and release a broad array of MMPs including their inhibitors. Further, MMPs are involved in A-NK cell basement membrane transmigration. Disintegration of tumour cell aggregates in vitro and digestion of Matrigel are interpreted as proteolytic effects. The additional matrix-dilating effect may be explained as a release of proteoglycans. The present studies confirm that intravital tumours largely resist derangement of the tumour structure in spite of A-NK cell infiltration.
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| 36. |
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| 37. |
- Albertsson, Per, 1956, et al.
(författare)
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Morbidity and use of medical resources in patients with chest pain and normal or near-normal coronary arteries.
- 1997
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Ingår i: The American journal of cardiology. - : Excerpta Medica, Inc.. - 0002-9149 .- 1879-1913. ; 79:3, s. 299-304
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate morbidity and use of medical resources in patients with chest pain and normal or near-normal coronary angiograms: 2,639 consecutive patients who underwent coronary angiograms due to chest pain were registered. Two years thereafter all patients who showed normal or near-normal coronary angiograms were approached with a questionnaire regarding hospitalization during the last 4 years (2 years before and 2 years after angiography). All medical files were also examined. Of the patients who underwent angiography, 163 (6%) had no significant stenoses, and of these, 113 showed complete normal angiograms and 50 showed mild (i.e. <50%) stenoses. During the 2 years before diagnostic angiogram, 66% of the patients were hospitalized compared with only 35% during 2 years after angiography (p <0.001). The reduction in hospitalization was due to curtailed utilization of medical resources for cardiac reasons; mean days in hospital was 6.6 days before angiography versus 2.8 days after (p <0.001). There were no significant differences in hospitalization when comparing patients with mild stenoses and completely normal angiograms. There were, furthermore, no differences between patients with positive or negative exercise tests. Thus, the need for hospitalization is significantly reduced after a diagnostic angiogram reveals normal or near-normal coronary arteries.
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| 38. |
- Albertsson, Per, 1964, et al.
(författare)
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On metronomic chemotherapy: modulation of angiogenesis mediated by VEGE-A
- 2006
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:2, s. 144-55
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Tidskriftsartikel (refereegranskat)abstract
- Tumors are angiogenesis dependent. Preclinical studies have shown that well-tolerated continuous low dose, i.e. metronomic, chemotherapy can exert significant antiangiogenic effects per se and thereby a greater antitumor influence than conventional chemotherapy with high, spaced-out bolus doses. There are however, no means of quantitatively assessing the antiangiogenic effect of chemotherapy in tumors. We therefore used a surrogate tumor-free, non-surgical rat mesentery model and quantitatively studied the dose effect of metronomic treatment with cisplatin, cyclophosphamide, doxorubicin, fluorouracil and paclitaxel on VEGF-A-mediated angiogenesis, a characteristic of tumors. Cyclophosphamide and paclitaxel treatment exerted significant dose-dependent antiangiogenic effects, whereas doxorubicin treatment produced insignificant effects. By contrast, metronomic cisplatin and fluorouracil treatment occasionally significantly stimulated angiogenesis in a dose-dependent, non-linear manner. To our knowledge, this is the first report of metronomic chemotherapy stimulating angiogenesis in vivo. The data suggest that the angiogenic response to cisplatin, cyclophosphamide, fluorouracil and paclitaxel was significantly influenced by the presence of antioxidants in the vehicles or when co-treated with N-acetylcystein, a widely used free-radical scavenger. The data relating to the metronomic scheduling were compared with bolus treatment data for the identical agent formulations in the same experimental model. Cisplatin, cyclophosphamide and paclitaxel caused approximately the same overall, agent-specific angiogenesis-modulating effects following metronomic and bolus treatments. Moreover, apparently secondary delayed effects of chemotherapy affected capillary sprouting.
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| 39. |
- Albertsson, Per, 1964, et al.
(författare)
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Positron emission tomography and computed tomographic (PET/CT) imaging for radiation therapy planning in anal cancer: A systematic review and meta-analysis
- 2018
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Ingår i: Critical reviews in oncology/hematology. - : Elsevier BV. - 1040-8428. ; 126, s. 6-12
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Forskningsöversikt (refereegranskat)abstract
- To improve the accuracy of chemoradiation therapy in anal cancer patients PET/CT is frequently used in the planning of radiation therapy. A systematic review was performed to assess impact on survival, quality of life, symptom score, change in target definition and treatment intention. Systematic literature searches were conducted in Medline, EMBASE, the Cochrane Library, and Centre for Reviews and Dissemination. Ten cross-sectional studies were identified. No data were available on survival or quality of life. The summary estimate of the proportion of patients in which PET/CT had an impact on the target definition, was 23% (95% CI 16;33). The corresponding summary estimate of a change in treatment intent from curative to palliative was 3% (95% CI 2;6). Almost one in four patients had a change in target definition, which supports the use of PET/CT in radiation therapy planning, but the consequence regarding survival and quality of life is still uncertain.
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| 40. |
- Albertsson, Per-Åke
(författare)
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A quantitative model of the domain structure of the photosynthetic membrane
- 2001
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Ingår i: Trends in Plant Science. - 1360-1385. ; 6:8, s. 349-358
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Tidskriftsartikel (refereegranskat)abstract
- A model is presented that gives a quantitative picture of the distribution of the photosynthetic components in the photosynthetic membrane of higher plants. A salient feature of the model is that most of the pigments are located in the grana where photosystem I and II carry out linear electron transport, whereas the stroma lamellae, which harbour <20% of the pigments, carry out photosystem-I-mediated cyclic electron transport. This arrangement derives from the observation that more pigments are associated with photosystem I, which therefore captures more quanta than photosystem II. The excess pigments associated with photosystem I are thought to be located in the stroma lamellae.
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| 41. |
- Albertsson, Per-Åke
(författare)
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A remarkable constancy in the relative amount of stroma lamellae of chloroplasts from plants, and its functional significance
- 2001
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Ingår i: PS2001 Proceedings. - 0643067116
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Konferensbidrag (refereegranskat)abstract
- A model is presented which gives a quantitative picture of the distribution of the photosynthetic components in the thylakoid membrane of higher plants. The model is based on fragmentation and separation analysis together with microscopy. A salient feature of the model is that over 80 per cent of the pigments are located in the grana where the two photosystems 1 and 2 produce oxygen, NADPH and ATP by the linear electron transport pathway while the stroma lamellae, which harbour less than 20 per cent of the pigments, carry out Photosystem 1 mediated cyclic electron transport coupled to ATP production. This arrangement derives from the observation that more pigments are associated with Photosystem 1 which therefore captures more quanta than Photosystem 2. The excess pigments associated with Photosystem 1 are suggested to be located in the stroma lamellae. Tentative numbers of the different photosystem and cytochrome b.f. complexes located in the different domains of the thylakoid membrane will be presented.
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Albertsson, Per-Åke, et al.
(författare)
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The constant proportion of grana and stroma lamellae in plant chloroplasts
- 2004
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Ingår i: Physiologia Plantarum. - 0031-9317. ; 121:2, s. 334-342
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Tidskriftsartikel (refereegranskat)abstract
- The relative proportion of stroma lamellae and grana end membranes was determined from electron micrographs of 58 chloroplasts from 21 different plant species. The percentage of grana end membranes varied between 1 and 21% of the total thylakoid membrane indicating a large variation in the size of grana stacks. By contrast the stroma lamellae account for 20.3 +/- 2.5 (SD)% of the total thylakoid membrane. A plot of percentage stroma lamellae against percentage of grana end membranes fits a straight line with a slope of zero showing that the proportion of stroma lamellae is independent of the size of the grana stacks. That stroma lamellae account for about 20% of the thylakoid membrane is in agreement with fragmentation and separation analysis (Gadjieva et al. Biochim. Biophys. Acta 144: 92-100, 1999). Chloroplasts from spinach, grown under high or low light, were fragmented by sonication and separated by countercurrent distribution into two vesicle populations originating from grana and stroma lamellae plus end membranes, respectively. The separation diagrams were very similar lending independent support for the notion that the proportion of stroma lamellae is constant. The results are discussed in relation to the composition and function of the chloroplast in plants grown under different environmental conditions, and in relation to a recent quantitative model for the thylakoid (Albertsson, Trends Plant Sci. 6: 349-354, 2001).
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| 46. |
- Albertsson, Per-Åke
(författare)
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The contribution of photosynthetic pigments to the development of biochemical separation methods: 1900-1980
- 2003
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Ingår i: Photosynthesis Research. - 0166-8595. ; 76:1-3, s. 217-225
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Forskningsöversikt (refereegranskat)abstract
- The role of photosynthetic pigments in the development of separation methods in biochemistry during the period 1900-1980 is described beginning with M. Tswett who introduced separation of chlorophylls and carotenoids on columns and coined the term chromatography in 1906. In Uppsala, T. Svedberg developed the ultracentrifuge in the 1920s. A. Tiselius improved electrophoresis in the 1930s and developed chromatography of proteins in the 1940s and 1950s. Others of `The Uppsala school in separation science' include J. Porath, P. Flodin and S. Hjertén who further developed various gel chromatographic methods. Hjertén introduced free zone electrophoresis in narrow tubes, a forerunner of capillary electrophoresis. Two proteins, phycoerythrin and phycocyanin, were used as test substances in all these methodological studies. Aqueous two-phase partitioning as a separation method was introduced in 1956 by the author. In this work, chloroplast particles were used, and the method was applied for the separation and purification of intact chloroplasts, inside-out thylakoid vesicles and plasma membranes. My research was carried out in cooperation with G. Blomquist, G. Johansson, C. Larsson, B. Andersson and H.-E. Akerlund during a 20-year period, 1960-1980.
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Andersson, Björn, 1939, et al.
(författare)
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Seasonal variations in vitamin D in relation to growth in short prepubertal children before and during first year growth hormone treatment
- 2015
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Ingår i: Journal of Endocrinological Investigation. - : Springer Science and Business Media LLC. - 0391-4097 .- 1720-8386. ; 38:12, s. 1309-1317
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Tidskriftsartikel (refereegranskat)abstract
- Purpose This study investigated the relationship between seasonal variations in 25-hydroxyvitamin D (25(OH) D) levels and growth in prepubertal children during both the pretreatment year and the first year of GH treatment. Methods The study included 249 short prepubertal children with a broad range of GH secretion, GH(max) during a 24 h profile median 23; range 1-127 mU/L, 191 boys (mean age +/- SD, 8.6 +/- 2.6 years), 58 girls (7.5 +/- 1.9 years) receiving GH treatment (mean 43 mu g/kg/day; range 17-99 mu g/kg/day). Serum 25(OH) D was measured using an automated IDS-iSYS immunoassay. Results 25(OH) D levels showed seasonal variation, and decreased significantly during GH treatment. 25(OH) D levels at start and first year reduction in 25(OH) D, correlated (-) with the first year growth response during treatment. The degree of GH secretion capacity within our study population of mainly non-GH deficient children and 25(OH) D sufficient (67 +/- 29 nmol/L) had no influence on 25(OH) D levels. Growth during GH treatment were independent of seasonal variations in 25(OH) D. Multiple regression analysis showed that 25(OH) D levels at treatment start, together with auxological data and IGF-binding protein-3(SDS), explained 61 % of the variation in first year gain in height(SDS). Conclusion 25(OH) D levels were associated with first year growth response to GH and may be a useful contribution to future growth prediction models.
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