| 1. |
- Andersson, Jonas, 1969-
(författare)
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Adipose tissue as an active organ : blood flow regulation and tissue-specific glucocorticoid metabolism
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Despite advances in the treatment of atherosclerosis, cardiovascular disease is the leading cause of death worldwide. With the population getting older and more obese, the burden of cardiovascular disease may further increase. Premenopausal women are relatively protected against cardiovascular disease compared to men, but the reasons for this sex difference are partly unknown. Redistribution of body fat from peripheral to central depots may be a contributing factor. Central fat is associated with hyperlipidemia, hyperglycemia, hypertension, and insulin resistance. Two possible mediators of these metabolic disturbances are tissue-specific production of the stress hormone cortisol and adipose tissue blood flow (ATBF). The aim of this thesis was to determine the adipose tissue production of cortisol by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and to investigate the regulation of ATBF. Materials and Methods: Cortisol release was estimated by labeled cortisol infusions and tissue-specific catheterizations of subcutaneous and visceral adipose tissue (VAT) in men. We investigated ATBF by 133Xe-washout and its relation to autonomic activity, endothelial function, adipose tissue distribution, and adipokines in different groups of women. We further investigated the effect of two diets and of weight loss on ATBF in women. Results: We demonstrated significant cortisol release from subcutaneous adipose tissue in humans. Splanchnic cortisol release was accounted for entirely by the liver. Cortisol release from VAT (to the portal vein) was not detected. ATBF decreased according to increasing weight and postmenopausal status, and the level of blood flow was associated with nitric oxide (NO) activity and autonomic activity. ATBF was also highly associated with leptin levels and both subcutaneous adipose tissue and VAT areas. After 6 months of diet and weight reduction, a significant difference in ATBF was observed between diet groups. Conclusions: Our data for the first time demonstrate the contributions of cortisol generated from subcutaneous adipose tissue, visceral tissues, and liver by 11β-HSD1. ATBF is linked to autonomic activity, NO activity, and the amount of adipose tissue (independent of fat depot). Postmenopausal overweight women exhibited a loss of ATBF flexibility, which may contribute to the metabolic dysfunction seen in this group. Weight loss in a diet program could not increase the ATBF, although there were ATBF differences between diet groups. The results will increase understanding of adipose tissue biology and contribute to the development of treatment strategies targeting obesity and obesity-related disorders.
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| 2. |
- Andersson, Jonas, et al.
(författare)
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Association of adipose tissue blood flow with fat depot sizes and adipokines in women
- 2012
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Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 36:6, s. 783-789
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore possible associations between adipose tissue (AT) blood flow (ATBF), AT depot sizes and adipocyte-derived hormones (adipokines) in women.Subjects: In all, 43 healthy women were divided into four groups: normal-weight (n=11) and obese (n=11) pre-menopausal women and normal-weight (n=10) and obese (n=11) post-menopausal women.Methods: Fasting levels of adipokines were obtained, and a single-slice computed tomography scan at the level of L4-L5 was used to estimate fat depot sizes. ATBF was assessed by xenon washout while in a fasting state and after oral glucose load. We also measured glucose, insulin and non-esterified fatty acids.Results: Total, subcutaneous and visceral AT areas strongly correlated with ATBF (all P<0.001). Circulating leptin levels strongly and inversely correlated with ATBF (P=0.001), but this association did not remain after adjustment for body mass index. Adiponectin was not associated with blood flow.Conclusion: ATBF is closely linked to subcutaneous and visceral AT size. Further analyses are needed to determine possible mediators of this association, including mechanistic studies to assess a putative role for leptin as a significant modulator of blood flow. International Journal of Obesity advance online publication, 26 July 2011; doi:10.1038/ijo.2011.152.
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| 3. |
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| 4. |
- Berner, Karin, et al.
(författare)
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Dose optimisation of double-contrast barium enema examinations.
- 2010
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Ingår i: Radiation protection dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 139:1-3, s. 388-392
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present work was to optimise the filtration and dose setting for double-contrast barium enema examinations using a Philips MultiDiagnost Eleva FD system. A phantom study was performed prior to a patient study. A CDRAD phantom was used in a study where copper and aluminium filtration, different detector doses and tube potentials were examined. The image quality was evaluated using the software CDRAD Analyser and the phantom dose was determined using the Monte Carlo-based software PCXMC. The original setting [100 % detector dose (660 nGy air kerma) and a total filtration of 3.5 mm Al, at 81 kVp] and two other settings identified by the phantom study (100 % detector dose and additional filtration of 1 mm Al and 0.2 mm Cu as well as 80 % detector dose and added filtration of 1 mm Al and 0.2 mm Cu) were included in the patient study. The patient study included 60 patients and up to 8 images from each patient. Six radiologists performed a visual grading characteristics study to evaluate the image quality. A four-step scale was used to judge the fulfillment of three image quality criteria. No overall statistical significant difference in image quality was found between the three settings (P > 0.05). The decrease in the effective dose for the settings in the patient study was 15 % when filtration was added and 34 % when both filtrations was added and detector dose was reduced. The study indicates that additional filtration of 1 mm Al and 0.2 mm Cu and a decrease in detector dose by 20 % from the original setting can be used in colon examinations with Philips MultiDiagnost Eleva FD to reduce the patient dose by 30 % without significantly affecting the image quality. For 20 exposures, this corresponds to a decrease in the effective dose from 1.6 to 1.1 mSv.
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| 5. |
- Boij, Mats, et al.
(författare)
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Betti numbers of graded modules and the multiplicity conjecture in the non-Cohen-Macaulay case
- 2012
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Ingår i: Algebra & Number Theory. - : Mathematical Sciences Publishers. - 1937-0652 .- 1944-7833. ; 6:3, s. 437-454
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Tidskriftsartikel (refereegranskat)abstract
- We use results of Eisenbud and Schreyer to prove that any Betti diagram of a graded module over a standard graded polynomial ring is a positive linear combination of Betti diagrams of modules with a pure resolution. This implies the multiplicity conjecture of Herzog, Huneke, and Srinivasan for modules that are not necessarily Cohen-Macaulay and also implies a generalized version of these inequalities. We also give a combinatorial proof of the convexity of the simplicial fan spanned by pure diagrams.
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| 6. |
- Carlander, Anna, et al.
(författare)
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The effect of radiation dose reduction on clinical image quality in chest radiography of premature neonates using a dual-side readout technique computed radiography system
- 2010
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Ingår i: Radiation protection dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 139:1-3, s. 275-280
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to investigate if the exposure could be reduced from the clinical setting (resulting in an effective dose of 8 microSv for a neonate of weight 0.7 kg and height 25 cm at a tube voltage of 90 kV) without negatively influencing the image quality for a dual-side readout technique computed radiography (CR) system in chest radiography of premature neonates. Chest radiographs of premature neonates were acquired with the double-side readout technique CR system. The images underwent simulated dose reduction in steps of 20 % to represent five different radiation dose levels. Four image quality criteria, related to the visibility of important anatomical structures, were used in a visual grading study where five experienced radiologists rated how well the criteria were fulfilled for all images. When reducing the radiation dose, a decrease in image quality could be observed already at the 80 % dose level for all the structures. The results indicate that a decrease in exposure from the clinically used setting affects the image quality negatively for the CR system.
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| 7. |
- Kronschläger, Martin, et al.
(författare)
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Pharmacokinetics for topically applied caffeine in the rat
- 2014
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Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835 .- 1096-0007. ; 122, s. 94-101
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Tidskriftsartikel (refereegranskat)abstract
- Topically applied caffeine was recently identified as a promising candidate molecule for cataract prevention. Little is known about the pharmacokinetics for topically applied caffeine. Potential toxicity of 72 mM caffeine on the ocular surface and the lens was qualitatively monitored and no toxic effects were observed. The concentration of caffeine was measured in the lens and the blood after topical application of 72 mM caffeine to groups of 10 animals sacrificed at 30, 60, 90 and 120 min after topical application. The lens concentration decreased throughout the observation period while the blood concentration increased up to 120 min. Further, the concentration of caffeine in the lens and blood was measured 30 min after topical application of caffeine, the concentration of caffeine being 0.72, 3.34, 15.51 and 72 mM depending on group belonging, in groups of 10 animals. The caffeine concentration in lens and blood, respectively, increased proportionally to the caffeine concentration topically applied. The rat blood concentrations achieved were far below the equivalent threshold dose of FDA recommended daily dose for humans. This information is important for further development of caffeine eye drops for cataract prevention.
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| 8. |
- Leuchowius, Karl-Johan, et al.
(författare)
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High content screening for inhibitors of protein interactions and post-translational modifications in primary cells by proximity ligation
- 2010
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 9:1, s. 178-183
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Tidskriftsartikel (refereegranskat)abstract
- The cost of developing new drugs is a major obstacle for pharmaceutical companies and academia with many drugs identified in the drug discovery process failing approval for clinical use due to lack of intended effect or because of severe side effects. Since the early 1990 s, high throughput screening of drug compounds has increased enormously in capacity but has not resulted in a higher success rate of the identified drugs. Thus, there is a need for methods that can identify biologically relevant compounds and more accurately predict in vivo effects early in the drug discovery process. To address this, we developed a proximity ligation-based assay for high content screening of drug effects on signaling pathways. As a proof of concept, we used the assay to screen through a library of previously identified kinase inhibitors, including six clinically used tyrosine kinase inhibitors, to identify compounds that inhibited the platelet-derived growth factor (PDGF) receptor beta signaling pathway in stimulated primary human fibroblasts. Thirteen of the 80 compounds were identified as hits, and the dose responses of these compounds were measured. The assay exhibited a very high Z' factor (0.71) and signal to noise ratio (11.7), demonstrating excellent ability to identify compounds interfering with the specific signaling event. A comparison with regular immunofluorescence detection of phosphorylated PDGF receptor demonstrated a far superior ability by the in situ proximity ligation assay to reveal inhibition of receptor phosphorylation. In addition, inhibitor-induced perturbation of protein-protein interactions of the PDGF signaling pathway could be quantified, further demonstrating the usefulness of the assay in drug discovery.
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| 9. |
- Margolin, Sara, et al.
(författare)
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A randomised feasibility/phase II study (SBG 2004-1) with dose-dense/tailored epirubicin, cyclophoshamide (EC) followed by docetaxel (T) or fixed dosed dose-dense EC/T versus T, doxorubicin and C (TAC) in node-positive breast cancer.
- 2011
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 50:1, s. 35-41
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to evaluate the feasibility of tailored and dose-dense epirubicin and cyclophosphamide followed by docetaxel as adjuvant breast cancer therapy. Material and methods. Patients with node-positive breast cancer received either four cycles of biweekly and tailored EC (epirubicin 38-60-75-90-105-120 mg/m(2), cyclophosphamide 450-600-900-1200 mg/m(2)) followed by four cycles of docetaxel (60-75-85-100 mg/m(2)) (arm A) or the same regimen with fixed doses (E(90)C(600) + 4 → T(75) + 4) (arm B) or docetaxel, doxorubicin and cyclophosphamide (T(75)A(50)C(500)) every three weeks for six cycles (arm C). All patients received G-CSF support and prophylactic ciprofloxacin. Results. One-hundred and twenty-four patients were randomised in the study. In the A, B and C arm, 17% 19% and 3% of the patients had one or more cycles delayed due to side-effects whereas 24%, 5% and 15% experienced a grade 3 infection or febrile neutropenia. After the introduction of an extra week between the EC and T parts in the A and B arms, grade 3 hand-foot-skin reactions were reduced from 5 to 0.2%. Twenty-nine percent (A and B) and 20% (C) of the patients were hospitalised due to side-effects. Discussion. Dose-dense and tailored EC/T can be given with manageable toxicity and is after adjustment presently studied in the phase III Panther trial.
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| 10. |
- Nilsson, Jonas, et al.
(författare)
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Tests of HPGe- and scintillation-based backpack γ-radiation survey systems.
- 2014
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Ingår i: Journal of Environmental Radioactivity. - : Elsevier BV. - 1879-1700 .- 0265-931X. ; 135:Apr 24, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- The performance of three different backpack-mounted γ-radiation survey systems has been investigated. The systems are based on a LaBr3:Ce detector and a NaI(Tl) detector both with active volume dimensions of 76.2 mm in diameter and 76.2 mm length and a 123% relative efficiency HPGe detector. The detection limits of the systems were tested in a controlled outdoor environment in Sweden, followed by field tests of the HPGe- and LaBr3:Ce-based systems at the site of a radioactive waste repository in Georgia (in the Caucasus region of Eurasia). The results showed that the high efficiency HPGe detector performed significantly better than similar sized LaBr3:Ce and NaI(Tl) detectors, however, the HPGe detector was significantly heavier than the other systems. The use of different analysis methods revealed that creating maps of the survey area was the best method for offline analysis of survey data collected from a large area. Using off-site personnel for analysis of the data proved to be beneficial.
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