| 1. |
- Alvarsson, Jonathan, et al.
(författare)
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Ligand-Based Target Prediction with Signature Fingerprints
- 2014
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 54:10, s. 2647-2653
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Tidskriftsartikel (refereegranskat)abstract
- When evaluating a potential drug candidate it is desirable to predict target interactions in silico prior to synthesis in order to assess, e.g., secondary pharmacology. This can be done by looking at known target binding profiles of similar compounds using chemical similarity searching. The purpose of this study was to construct and evaluate the performance of chemical fingerprints based on the molecular signature descriptor for performing target binding predictions. For the comparison we used the area under the receiver operating characteristics curve (AUC) complemented with net reclassification improvement (NRI). We created two open source signature fingerprints, a bit and a count version, and evaluated their performance compared to a set of established fingerprints with regards to predictions of binding targets using Tanimoto-based similarity searching on publicly available data sets extracted from ChEMBL. The results showed that the count version of the signature fingerprint performed on par with well-established fingerprints such as ECFP. The count version outperformed the bit version slightly; however, the count version is more complex and takes more computing time and memory to run so its usage should probably be evaluated on a case-by-case basis. The NRI based tests complemented the AUC based ones and showed signs of higher power.
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| 2. |
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| 3. |
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| 4. |
- Lofvenborg, J. E., et al.
(författare)
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Coffee consumption and the risk of latent autoimmune diabetes in adults-results from a Swedish case-control study
- 2014
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Ingår i: Diabetic Medicine. - : Wiley. - 1464-5491 .- 0742-3071. ; 31:7, s. 799-805
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Tidskriftsartikel (refereegranskat)abstract
- Aims Coffee consumption is associated with a reduced risk of Type2 diabetes. Our aim was to investigate if coffee intake may also reduce the risk of latent autoimmune diabetes in adults, an autoimmune form of diabetes with features of Type2 diabetes. Methods We used data from a population-based case-control study with incident cases of adult onset (35years) diabetes, including 245 cases of latent autoimmune diabetes in adults (glutamic acid decarboxylase antibody positive), 759 cases of Type2 diabetes (glutamic acid decarboxylase antibody negative), together with 990 control subjects without diabetes, randomly selected from the population. Using questionnaire information on coffee consumption, we estimated the odds ratio of latent autoimmune diabetes in adults and Type2 diabetes adjusted for age, sex, BMI, smoking, physical activity, alcohol, education and family history of diabetes. Results Coffee intake was inversely associated with Type2 diabetes (odds ratio0.92, 95%CI 0.87-0.98 per cup/day). With regard to latent autoimmune diabetes in adults, the general trend was weak (odds ratio1.04, 95%CI 0.96-1.13), but stratification by degree of autoimmunity (median glutamic acid decarboxylase antibody levels) suggested that coffee intake may be associated with an increased risk of high glutamic acid decarboxylase antibody latent autoimmune diabetes in adults (odds ratio1.11, 95%CI 1.00-1.23 per cup/day). Furthermore, for every additional cup of coffee consumed per day, there was a 15.2% (P=0.0268) increase in glutamic acid decarboxylase antibody levels. Conclusions Our findings confirm that coffee consumption is associated with a reduced risk of Type2 diabetes. Interestingly, the findings suggest that coffee may be associated with development of autoimmunity and possibly an increased risk of more Type1-like latent autoimmune diabetes in adults.
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| 5. |
- Löfvenborg, J E, et al.
(författare)
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Fatty fish consumption and risk of latent autoimmune diabetes in adults
- 2014
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Ingår i: Nutrition & Diabetes. - : Springer Science and Business Media LLC. - 2044-4052. ; 4, s. e139-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: It has been suggested that intake of fatty fish may protect against both type 1 and type 2 diabetes. Hypotheses rest on the high marine omega-3 fatty acid eicosapentaenoic acid+docosahexaenoic acid (EPA+DHA) and vitamin D contents, with possible beneficial effects on immune function and glucose metabolism. Our aim was to investigate, for the first time, fatty fish consumption in relation to the risk of latent autoimmune diabetes in adults (LADA).METHODS: Analyses were based on data from a Swedish case-control study with incident cases of LADA (n=89) and type 2 diabetes (n=462) and randomly selected diabetes-free controls (n=1007). Diabetes classification was based on the onset of age (⩾35), glutamic acid decarboxylase autoantibodies, and C-peptide. A validated food frequency questionnaire was used to derive information on previous intake of fish, polyunsaturated long-chain omega-3 fatty acids (n-3 PUFA) and supplementation of fish oil and vitamin D. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression, adjusted for age, gender, body mass index (BMI), family history of diabetes, physical activity, smoking, education, and consumption of alcohol, fruit, vegetables and red meat.RESULTS: Weekly fatty fish consumption (⩾1 vs <1 serving per week), was associated with a reduced risk of LADA but not type 2 diabetes (OR 0.51, 95% CI 0.30-0.87, and 1.01, 95% CI 0.74-1.39, respectively). Similar associations were seen for estimated intake of n-3 PUFA (⩾0.3 g per day; LADA: OR 0.60, 95% CI 0.35-1.03, type 2 diabetes: OR 1.14, 95% CI 0.79-1.58) and fish oil supplementation (LADA: OR 0.47, 95% CI 0.19-1.12, type 2 diabetes: OR 1.58, 95% CI 1.08-2.31).CONCLUSIONS: Our findings suggest that fatty fish consumption may reduce the risk of LADA, possibly through effects of marine-originated omega-3 fatty acids.
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| 6. |
- Rasouli, Bahareh, et al.
(författare)
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Alcohol and the risk for LADA: results based on the Swedish ESTRID study.
- 2014
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 171:5, s. 535-543
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Tidskriftsartikel (refereegranskat)abstract
- Objective Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. Our aim was to investigate whether alcohol consumption is associated with risk of latent autoimmune diabetes in adults (LADA), an autoimmune form of diabetes with features of type 2 diabetes. Design Population-based case-control study Methods We used data from ESTRID case-control study carried out between 2010 and 2013, including 250 incident cases of LADA (glutamic acid decarboxylase antibodies [GADA] positive) and 764 cases of type 2 diabetes (GADA negative), and 1012 randomly selected controls aged ≥35. Logistic regression was used to estimate the odds ratios (OR) of diabetes in relation to alcohol intake, adjusted for age, sex, BMI, family history of diabetes, smoking, and education. Results Alcohol consumption was inversely associated with the risk of type 2 diabetes (OR 0.95, 95% confidence interval (CI); 0.92-0.99 for every 5-g increment in daily intake). Similar results were seen for LADA, but stratification by median GADA levels revealed that the results only pertained to LADA with low GADA (OR 0.85; 95% 0.76-0.94 per 5g alcohol/day), whereas no association was seen with LADA high GADA (OR 1.00, 95% CI; 0.94-1.06 per 5g/day). Every 5-g increment of daily alcohol intake was associated with a 10% increase in GADA levels (p=0.0312), and a10% reduction in HOMA-IR (p=0.0418). Conclusions Our findings indicate that alcohol intake may reduce risk of type 2 diabetes and type 2-like LADA, but has no beneficial effects on diabetes-related autoimmunity.
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| 7. |
- Rasouli, Bahareh, et al.
(författare)
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Alcohol and the risk for latent autoimmune diabetes in adults : results based on Swedish ESTRID study
- 2014
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 171:5, s. 535-543
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. Our aim was to investigate whether alcohol consumption is associated with the risk of latent autoimmune diabetes in adults (LADA), an autoimmune form of diabetes with features of type 2 diabetes. Design: A population-based case-control study was carried out to investigate the association of alcohol consumption and the risk of LADA. Methods: We used data from the ESTRID case-control study carried out between 2010 and 2013, including 250 incident cases of LADA (glutamic acid decarboxylase antibodies (GADAs) positive) and 764 cases of type 2 diabetes (GADA negative), and 1012 randomly selected controls aged >= 35. Logistic regression was used to estimate the odds ratios (ORs) of diabetes in relation to alcohol intake, adjusted for age, sex, BMI, family history of diabetes, smoking, and education. Results: Alcohol consumption was inversely associated with the risk of type 2 diabetes (OR 0.95, 95% CI 0.92-0.99 for every 5-g increment in daily intake). Similar results were observed for LADA, but stratification by median GADA levels revealed that the results only pertained to LADA with low GADA levels (OR 0.85, 95% CI 0.76-0.94/5 g alcohol per day), whereas no association was observed with LADA having high GADA levels (OR 1.00, 95% CI 0.94-1.06/5 g per day). Every 5-g increment of daily alcohol intake was associated with a 10% increase in GADA levels (P=0.0312), and a 10% reduction in homeostasis model assessment of insulin resistance (P=0.0418). Conclusions: Our findings indicate that alcohol intake may reduce the risk of type 2 diabetes and type 2-like LADA, but has no beneficial effects on diabetes-related autoimmunity.
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| 8. |
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| 9. |
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| 10. |
- Aleman, Soo, et al.
(författare)
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A Risk for Hepatocellular Carcinoma Persists Long-term After Sustained Virologic Response in Patients With Hepatitis C-Associated Liver Cirrhosis
- 2013
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 57:2, s. 230-236
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Tidskriftsartikel (refereegranskat)abstract
- Background. The long-term effect of sustained virologic response (SVR) to antiviral therapy on the risk of developing hepatocellular carcinoma (HCC), liver complications, liver-related death, and overall death in hepatitis C virus (HCV)-infected patients with liver cirrhosis is not fully known. Methods. These risks were evaluated during long-term follow-up in 351 patients with HCV-related cirrhosis. One hundred ten patients with SVR, 193 with non-SVR, and 48 who were untreated were included in a multicenter cohort that was initiated in 2001 and prospectively followed up for a mean of 5.3 (SD, 2.8) years. Complementary follow-up data from national registries were used to minimize the loss of patients during follow-up. Results. Six patients with SVR developed HCC at 0.04, 0.64, 2.4, 7.4, 7.4, and 7.6 years, respectively, after achieving SVR. The incidences of HCC, any liver complication, liver-related death, and overall death per 100 person-years were significantly lower in SVR time with 1.0, 0.9, 0.7, and 1.9, compared to 2.3, 3.2, 3.0, and 4.1 in non-SVR and 4.0, 4.9, 4.5, and 5.1 in untreated time. The long-term consequences did not decline significantly after >3 years versus during the first 3 years of follow-up. Conclusions. The risk for HCC, liver decompensation, and death in patients with liver cirrhosis related to HCV was markedly reduced after SVR, but a long-term risk of developing HCC remains for up to 8 years. Cirrhotic patients with HCV who achieve SVR should therefore maintain long-term surveillance for HCC. Future studies aimed to better identify those with remaining long-term risk for HCC are needed.
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| 11. |
- Alvarsson, Jonathan, et al.
(författare)
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Benchmarking Study of Parameter Variation When Using Signature Fingerprints Together with Support Vector Machines
- 2014
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 54:11, s. 3211-3217
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Tidskriftsartikel (refereegranskat)abstract
- QSAR modeling using molecular signatures and support vector machines with a radial basis function is increasingly used for virtual screening in the drug discovery field. This method has three free parameters: C, ?, and signature height. C is a penalty parameter that limits overfitting, ? controls the width of the radial basis function kernel, and the signature height determines how much of the molecule is described by each atom signature. Determination of optimal values for these parameters is time-consuming. Good default values could therefore save considerable computational cost. The goal of this project was to investigate whether such default values could be found by using seven public QSAR data sets spanning a wide range of end points and using both a bit version and a count version of the molecular signatures. On the basis of the experiments performed, we recommend a parameter set of heights 0 to 2 for the count version of the signature fingerprints and heights 0 to 3 for the bit version. These are in combination with a support vector machine using C in the range of 1 to 100 and gamma in the range of 0.001 to 0.1. When data sets are small or longer run times are not a problem, then there is reason to consider the addition of height 3 to the count fingerprint and a wider grid search. However, marked improvements should not be expected.
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| 12. |
- Asad, Samina, et al.
(författare)
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HTR1A a Novel Type 1 Diabetes Susceptibility Gene on Chromosome 5p13-q13
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD less than= 2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes. Methodology/Principal Findings: Microsatellites were genotyped in the Scandinavian families to fine-map the previously linked region. Further, SNPs were genotyped in Swedish and Danish families as well as Swedish sporadic cases. In the Swedish families we detected genome-wide significant linkage to the 5-hydroxytryptamine receptor 1A (HTR1A) gene (LOD 3.98, pless than9.8x10(-6)). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (pless than0.002, pless than0.001 respectively). The association was not confirmed in sporadic cases. Conditional analysis indicates that the primary association was to HTR1A. Quantitative PCR show that transcripts of both HTR1A and RNF180 are present in human islets of Langerhans. Moreover, immunohistochemical analysis confirmed the presence of the 5-HTR1A protein in isolated human islets of Langerhans as well as in sections of human pancreas. Conclusions: We have identified and confirmed the association of both HTR1A and RFN180, two genes in high linkage disequilibrium (LD) to T1D in two separate family materials. As both HTR1A and RFN180 were expressed at the mRNA level and HTR1A as protein in human islets of Langerhans, we suggest that HTR1A may affect T1D susceptibility by modulating the initial autoimmune attack or either islet regeneration, insulin release, or both.
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| 13. |
- Barbu, Andreea, et al.
(författare)
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Blood flow in endogenous and transplanted pancreatic islets in anesthetized rats : Effects of lactate and pyruvate
- 2012
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Ingår i: Pancreas. - 0885-3177 .- 1536-4828. ; 41:8, s. 1263-1271
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of this study was to evaluate the effects of exogenously administered lactate and pyruvate on blood perfusion in endogenous and transplanted islets. METHODS: Anesthetized Wistar-Furth rats were given lactate or pyruvate intravenously, and regional blood perfusion was studied 3 or 30 minutes later with a microsphere technique. Separate rats received a 30-minute infusion of pyruvate or lactate into the portal vein before blood flow measurements. We also administered these substances to islet-implanted rats 4 weeks after transplantation and measured graft blood flow with laser Doppler flowmetry. The expression of monocarboxylate transporter 1 and lactate dehydrogenase A was analyzed. RESULTS: The expression of monocarboxylate transporter 1 and lactate dehydrogenase A was markedly up-regulated in transplanted as compared with endogenous islets. Administration of pyruvate, but not lactate, increased mesenteric blood flow after 3 minutes. Pyruvate decreased mesenteric blood flow after 30 minutes, whereas lactate decreased only islet blood flow. These responses were absent in transplanted animals. A continuous intraportal infusion of lactate or pyruvate increased selectively islet blood flow but did not affect blood perfusion of transplanted islets. CONCLUSIONS: Lactate and pyruvate affect islet blood flow through effects mediated by interactions between the liver and the nervous system. Such a response can help adjust the release of islet hormones during excess substrate concentrations.
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| 14. |
- Bratt, Ola, et al.
(författare)
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The Study of Active Monitoring in Sweden (SAMS) : A randomized study comparing two different follow-up schedules for active surveillance of low-risk prostate cancer
- 2013
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 47:5, s. 347-355
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Forskningsöversikt (refereegranskat)abstract
- Objective. Only a minority of patients with low-risk prostate cancer needs treatment, but the methods for optimal selection of patients for treatment are not established. This article describes the Study of Active Monitoring in Sweden (SAMS), which aims to improve those methods. Material and methods. SAMS is a prospective, multicentre study of active surveillance for low-risk prostate cancer. It consists of a randomized part comparing standard rebiopsy and follow-up with an extensive initial rebiopsy coupled with less intensive follow-up and no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS-ObsQoL). Quality of life is assessed with questionnaires and compared with patients receiving primary curative treatment. SAMS-FU is planned to randomize 500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The primary endpoint is conversion to active treatment. The secondary endpoints include symptoms, distant metastases and mortality. All patients will be followed for 10-15 years. Results. Inclusion started in October 2011. In March 2013, 148 patients were included at 13 Swedish urological centres. Conclusions. It is hoped that the results of SAMS will contribute to fewer patients with indolent, low-risk prostate cancer receiving unnecessary treatment and more patients on active surveillance who need treatment receiving it when the disease is still curable. The less intensive investigational follow-up in the SAMS-FU trial would reduce the healthcare resources allocated to this large group of patients if it replaced the present standard schedule.
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| 15. |
- Bryland, Anna, et al.
(författare)
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Citrate treatment reduces endothelial death and inflammation under hyperglycaemic conditions.
- 2012
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Ingår i: Diabetes & Vascular Disease Research. - : SAGE Publications. - 1752-8984 .- 1479-1641. ; 9:1, s. 42-51
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Tidskriftsartikel (refereegranskat)abstract
- Hyperglycaemia and glucose degradation products (GDPs) are closely associated with oxidative stress and inflammation in diabetic patients, a condition that leads to endothelial dysfunction and cardiovascular problems. We evaluated the effect of citrate and gluconate on glucose- and GDP-induced endothelial inflammation by measuring changes in viability, inflammation and function in primary human umbilical vein endothelial cells (HUVECs). The extent of apoptosis/necrosis was measured by flow cytometry and visualised with confocal microscopy by staining with annexin V or propidium iodide, respectively. Protein kinase C-βII (PKC-βII) activation was evaluated with Western blotting. Incubation with glucose (30 mM) and GDP (50 µM) significantly increased PKC-βII expression, endothelial cell death and inflammation. The addition of citrate decreased hyperglycaemia-induced apoptosis (p = 0.021), necrosis (p = 0.04) and reduced PKC-βII expression (p = 0.021) down to background levels. Citrate improved endothelial function by reducing the inflammatory markers(p = 0.01) and by decreasing neutrophil diapedesis (p = 0.012). These results suggest that citrate may have therapeutic potential by reducing hyperglycaemia-induced endothelial inflammation and abolishing endothelial dysfunction.
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| 16. |
- Bryland, Anna, et al.
(författare)
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Infusion fluids contain harmful glucose degradation products.
- 2010
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; May 4, s. 1213-1220
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Glucose degradation products (GDPs) are precursors of advanced glycation end products (AGEs) that cause cellular damage and inflammation. We examined the content of GDPs in commercially available glucose-containing infusion fluids and investigated whether GDPs are found in patients' blood. METHODS: The content of GDPs was examined in infusion fluids by high-performance liquid chromatography (HPLC) analysis. To investigate whether GDPs also are found in patients, we included 11 patients who received glucose fluids (standard group) during and after their surgery and 11 control patients receiving buffered saline (control group). Blood samples were analyzed for GDP content and carboxymethyllysine (CML), as a measure of AGE formation. The influence of heat-sterilized fluids on cell viability and cell function upon infection was investigated. RESULTS: All investigated fluids contained high concentrations of GDPs, such as 3-deoxyglucosone (3-DG). Serum concentration of 3-DG increased rapidly by a factor of eight in patients receiving standard therapy. Serum CML levels increased significantly and showed linear correlation with the amount of infused 3-DG. There was no increase in serum 3-DG or CML concentrations in the control group. The concentration of GDPs in most of the tested fluids damaged neutrophils, reducing their cytokine secretion, and inhibited microbial killing. CONCLUSIONS: These findings indicate that normal standard fluid therapy involves unwanted infusion of GDPs. Reduction of the content of GDPs in commonly used infusion fluids may improve cell function, and possibly also organ function, in intensive-care patients.
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| 17. |
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| 18. |
- Carlsson, Lars, et al.
(författare)
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Model building in Bioclipse Decision Support applied to open datasets
- 2012
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Ingår i: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 211:Suppl., s. S62-
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Tidskriftsartikel (refereegranskat)abstract
- Bioclipse Decision Support (DS) is a system capable of building predictive models of any collection of SAR data, and making them available in a simple user interface based on Bioclipse (www.bioclipse.net).The method is fast and uses Faulon Signatures as chemical descriptors together with a Support Vector Machine algorithm for QSAR model building. A key feature is the capability to visualize and interpret results by highlighting the substructures which contributed most to the prediction. This, together with very fast predictions, allows for editing chemical structures with instantly updated results.We here present the results from applying Bioclipse Decision Support to several open QSAR data sets, including endpoints from OpenTox and PubChem. The results show how to extract data from the sources and to build models which can be integrated with user specific models.
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| 19. |
- Carlsson, Lars, et al.
(författare)
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Use of Historic Metabolic Biotransformation Data as a Means of Anticipating Metabolic Sites Using MetaPrint2D and Bioclipse
- 2010
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 11, s. 362-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Predicting metabolic sites is important in the drug discovery process to aid in rapid compound optimisation. No interactive tool exists and most of the useful tools are quite expensive.Results: Here a fast and reliable method to analyse ligands and visualise potential metabolic sites is presented which is based on annotated metabolic data, described by circular fingerprints. The method is available via the graphical workbench Bioclipse, which is equipped with advanced features in cheminformatics.Conclusions: Due to the speed of predictions (less than 50 ms per molecule), scientists can get real time decision support when editing chemical structures. Bioclipse is a rich client, which means that all calculations are performed on the local computer and do not require network connection. Bioclipse and MetaPrint2D are free for all users, released under open source licenses, and available from http://www.bioclipse.net.
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| 20. |
- Carlsson, Michael, et al.
(författare)
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Different fractions of human serum glycoproteins bind galectin-1 or galectin-8, and their ratio may provide a refined biomarker for pathophysiological conditions in cancer and inflammatory disease
- 2012
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Ingår i: Biochimica et Biophysica Acta - General Subjects. - : Elsevier. - 0304-4165 .- 1872-8006 .- 0006-3002. ; 1820:9, s. 1366-1372
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Tidskriftsartikel (refereegranskat)abstract
- Background: Changes in glycosylation of serum proteins are common, and various glycoforms are being explored as biomarkers in cancer and inflammation. We recently showed that glycoforms detected by endogenous galectins not only provide potential biomarkers, but also have different functions when they encounter galectins in tissue cells. Now we have explored the use of a combination of two galectins with different specificities, to further increase biomarker sensitivity and specificity. less thanbrgreater than less thanbrgreater thanMethods: Sera from 14 women with metastatic breast cancer, 12 healthy controls, 14 patients with IgA-nephritis (IgAN), and 12 patients with other glomerulonephritis were fractionated by affinity chromatography on immobilized human galectin-1 or galectin-8N, and the protein amounts of the bound and unbound fractions for each galectin were determined. less thanbrgreater than less thanbrgreater thanResults: Each galectin bound largely different fractions of the serum glycoproteins, including different glycoforms of haptoglobin. In the cancer sera, the level of galectin-1 bound glycoproteins was higher and galectin-8N bound glycoproteins lower compared to the other patients groups, whereas in IgAN sera the level of galectin-8N bound glycoproteins were higher. less thanbrgreater than less thanbrgreater thanConclusion: The ratio of galectin-1 bound/galectin-8N bound glycoproteins showed high discriminatory power between cancer patients and healthy, with AUC of 0.98 in ROC analysis, and thus provides an interesting novel cancer biomarker candidate. less thanbrgreater than less thanbrgreater thanGeneral significance: The galectin-binding ability of a glycoprotein is not only a promising biomarker candidate but may also have a specific function when the glycoprotein encounters the galectin in tissue cells, and thus be related to the pathophysiological state of the patient. This article is part of a Special Issue entitled Glycoproteomics.
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| 21. |
- Carlsson, Michael, et al.
(författare)
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Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins
- 2012
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Ingår i: Journal of Clinical Immunology. - : Springer Verlag (Germany). - 0271-9142 .- 1573-2592. ; 32:2, s. 246-255
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Tidskriftsartikel (refereegranskat)abstract
- Background Immunoglobulin A nephritis (IgAN) is the most common primary glomerulonephritis worldwide. It is caused by accumulation of IgA1-containing immune complexes in the kidney resulting in renal failure, which is thought to be due to altered glycosylation of IgA with a decrease of 2-3-sialylated galactosides (NeuAc alpha 2-3Gal). less thanbrgreater than less thanbrgreater thanPurpose The purpose of this study was to analyze whether altered glycosylation of IgA would lead to an altered binding to galectin-8, an endogenous lectin with strong affinity for 2-3-sialylated galactosides. Galectins are a family of beta-galactoside-binding proteins; by binding various glycoproteins, they play important roles in the regulation of cellular functions in inflammation and immunity. Hence, an altered binding of IgA to galectin-8 could lead to pathologic immune functions, such as glomerulonephritis. less thanbrgreater than less thanbrgreater thanMethods Affinity chromatography of serum glycoproteins on the human sialogalactoside-binding lectin galectin-8N permitted quantitation of bound and unbound fractions, including IgA. less thanbrgreater than less thanbrgreater thanResults Analysis of similar to 100 IgA nephritis sera showed that the galectin-8N unbound fraction of IgA increased compared to similar to 100 controls, consistent with the known loss of galactosylation. A subgroup of similar to 15% of the IgAN patients had a ratio of galectin-8 bound/unbound IgA andlt;0.09, not found for any of the controls. Unexpectedly, the galectin-8N-binding fraction of serum glycoproteins other than IgA increased in the sera of IgAN patients but not in controls, suggesting a previously unrecognized change in this disease. less thanbrgreater than less thanbrgreater thanConclusion This is the first study that relates a galectin, an endogenous lectin family, to IgA nephritis and thus should stimulate new avenues of research into the pathophysiology of the disease.
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| 22. |
- Carlsson, Per-Ola
(författare)
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Influence of microenvironment on engraftment of transplanted beta-cells
- 2011
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 116:1, s. 1-7
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Forskningsöversikt (refereegranskat)abstract
- Pancreatic islet transplantation into the liver provides a possibility to treat selected patients with brittle type 1 diabetes mellitus. However, massive early beta beta-cell death increases the number of islets needed to restore glucose homeostasis. Moreover, late dysfunction and death contribute to the poor long-term results of islet transplantation on insulin independence. Studies in recent years have identified early and late challenges for transplanted pancreatic islets, including an instant blood-mediated inflammatory reaction when exposing human islets to the blood microenvironment in the portal vein and the low oxygenated milieu of islets transplanted into the liver. Poor revascularization of remaining intact islets combined with severe changes in the gene expression of islets transplanted into the liver contributes to late dysfunction. Strategies to overcome these hurdles have been developed, and some of these interventions are now even tested in clinical trials providing a hope to improve results in clinical islet transplantation. In parallel, experimental and clinical studies have, based on the identified problems with the liver site, evaluated the possibility of change of implantation organ in order to improve the results. Site-specific differences clearly exist in the engraftment of transplanted islets, and a more thorough characterization of alternative locations is needed. New strategies with modifications of islet microenvironment with cells and growth factors adhered to the islet surface or in a surrounding matrix could be designed to intervene with site-specific hurdles and provide possibilities to improve future results of islet transplantation.
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| 23. |
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| 24. |
- Carlsson, Stefan, et al.
(författare)
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Current routines for transrectal ultrasound-guided prostate biopsy: A web-based survey by the Swedish Urology Network
- 2012
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 46:6, s. 405-410
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Tidskriftsartikel (refereegranskat)abstract
- Objective. This study aimed to survey current Swedish practices for performing and handling transrectal ultrasound-guided prostate biopsies. Material and methods. A Swedish Urology Network (SUNe) was organized for the distribution of information, survey studies and research collaborations. A web-based questionnaire was distributed to the members in 2011. Results. In this first SUNe survey, 137 (91%) of the 151 members replied. All used antibiotic prophylaxis (84% ciprofloxacin, 12% trimethoprim-sulfamethoxazole), most commonly (63%) as a single dose of ciprofloxacin. Local anaesthesia was used by 87%. Half of the respondents only used a "side-fire" probe, whereas 17% always used an "end-fire" probe. Most (84%) routinely took 10 or more biopsy cores. About three-quarters started with the right base of the prostate and did not routinely take midline biopsies. More than one-third never or rarely sampled the anterior part of the prostate. There was great variability in how biopsy location was reported, but 71% considered a national standardized coordinate system desirable. Fine-needle aspiration was used occasionally by 39%, in more than 10% of cases by 6% and always by 2%. Most urologists mounted the biopsy cores on paper before fixation (78%), put only one core per jar (75%) and used flat-bottomed jars (70%). Conclusions. Most routines for handling of prostate biopsies, antibiotic prophylaxis, local anaesthesia and number of cores were uniform. However, there is still a need for standardization of the performance of ultrasound-guided biopsies. Although the method used to specify biopsy location varied greatly, most urologists would prefer a national standardized system.
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| 25. |
- Christoffersson, Gustaf, et al.
(författare)
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Clinical and Experimental Pancreatic Islet Transplantation to Striated Muscle : Establishment of a Vascular System Similar to that in Native Islets
- 2010
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:10, s. 2569-2578
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Curing type 1 diabetes by transplanting pancreatic islets into the liver is associated with poor long-term outcome and graft failure at least partly due to inadequate graft revascularization. The aim of the current study was to evaluate striated muscle as a potential angiogenic site for islet transplantation. Research Design and Methods: The current study presents a new experimental model which is found applicable to clinical islet transplantation. Islets were implanted into striated muscle where after intra-islet vascular density and blood flow were visualized with intravital and confocal microscopy in mice, and by magnetic resonance imaging in three auto-transplanted pancreatectomized patients. Mice were rendered neutropenic by repeated injections of Gr-1 antibody and diabetes was induced by alloxan treatment. Results: Contrary to liver-engrafted islets, islets transplanted to mouse muscle were revascularized with vessel densities and blood flow entirely comparable to islets within intact pancreas. Initiation of islet revascularization at the muscular site was dependent on neutrophils, and the function of islets transplanted to muscle was proven by curing diabetic mice. The experimental data were confirmed in auto-transplanted patients where higher plasma volumes were measured in islets engrafted in forearm muscle compared to adjacent muscle tissue through high-resolution magnetic resonance imaging. Conclusions: This study presents a novel paradigm in islet transplantation whereby recruited neutrophils are crucial for the functionally restored intra-islet blood perfusion following transplantation to striated muscle under experimental and clinical situations.
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| 26. |
- Christoffersson, Gustaf, et al.
(författare)
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Intramuscular islet transplantation promotes restored islet vascularity
- 2011
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Ingår i: Islets. - : Informa UK Limited. - 1938-2014 .- 1938-2022. ; 3:2, s. 69-71
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In a recent publication, we reported that islets transplanted to mouse striated muscle became revascularized with intra-islet vessel densities comparable to native islets. Revascularization of islet grafts was completely dependent on recruited Gr-1+ leukocytes. Diabetic mice cured by transplantation of 300 islets into muscle handled glucose tolerance tests as healthy controls, whereas mice cured by intraportal islet transplantation into the liver had increased blood glucose values during the load. The translational impact of these observations were confirmed by magnetic resonance imaging of autotransplanted islets in the forearm muscle of pancreactomized patients, and higher blood perfusion of the grafts compared to adjacent muscle were found. In summary, the striated muscle is a promising site for islet transplantation which promotes full revascularization of implanted grafts. The proangiogenic role of recruited leukocytes during engraftment needs to be further characterized, and considered for immune suppression treatments.
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| 27. |
- Dellson, Pia, et al.
(författare)
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Towards optimised information about clinical trials; identification and validation of key issues in collaboration with cancer patient advocates.
- 2011
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Ingår i: European Journal of Cancer Care. - : Hindawi Limited. - 1365-2354 .- 0961-5423. ; 20, s. 445-454
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Tidskriftsartikel (refereegranskat)abstract
- DELLSON P., NILBERT M., BENDAHL P-O., MALMSTROM P. & CARLSSON C. (2010) European Journal of Cancer Care Towards optimised information about clinical trials; identification and validation of key issues in collaboration with cancer patient advocates Clinical trials are crucial to improve cancer treatment but recruitment is difficult. Optimised patient information has been recognised as a key issue. In line with the increasing focus on patients' perspectives in health care, we aimed to study patients' opinions about the written information used in three clinical trials for breast cancer. Primary data collection was done in focus group interviews with breast cancer patient advocates. Content analysis identified three major themes: comprehensibility, emotions and associations, and decision making. Based on the advocates' suggestions for improvements, 21 key issues were defined and validated through a questionnaire in an independent group of breast cancer patient advocates. Clear messages, emotionally neutral expressions, careful descriptions of side effects, clear comparisons between different treatment alternatives and information about the possibility to discontinue treatment were perceived as the most important issues. Patients' views of the information in clinical trials provide new insights and identify key issues to consider in optimising future written information and may improve recruitment to clinical cancer trials.
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| 28. |
- Drott, Carl Johan, et al.
(författare)
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Sustained Beta-Cell Dysfunction but Normalized Islet Mass in Aged Thrombospondin-1 Deficient Mice
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10, s. e47451-
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1), that showed to be of importance for islet angiogenesis and beta-cell function in young mice. The present study aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. Islet and beta-cell mass were observed increased at 10-12 weeks of age in TSP-1 deficient mice, but were normalized before 16 weeks of age when compared to wild-type controls. Islet vascularity was normal in 10-12 and 16-week-old TSP-1 deficient animals, whereas islets of one-year-old animals lacking TSP-1 were hypervascular. Beta-cell dysfunction in TSP-1 deficient animals was present at similar magnitudes between 10-12 and 52 weeks of age, as evaluated by glucose tolerance tests. The insulin secretion capacity in vivo of islets in one-year-old TSP-1 deficient animals was only similar to 15% of that in wild-type animals. Using a transplantation model, we reconstituted TSP-1 in adult TSP-deficient islets. In contrast to neonatal TSP-1 deficient islets that we previously reported to regain function after TSP-1 reconstitution, adult islets failed to recover. We conclude that TSP-1 deficiency in islets causes changing vascular and endocrine morphological alterations postnatally, but is coupled to a chronic beta-cell dysfunction. The beta-cell dysfunction induced by TSP-1 deficiency is irreversible if not substituted early in life.
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| 29. |
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| 30. |
- Eriksson, Olof, et al.
(författare)
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The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas
- 2014
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:10, s. 3428-3437
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Tidskriftsartikel (refereegranskat)abstract
- In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [(11)C]5-Hydroxy-Tryptophan ([(11)C]5-HTP).A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.[(11)C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [(11)C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.
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| 31. |
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| 32. |
- Espes, Daniel, et al.
(författare)
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Increased Circulating Betatrophin Concentrations in Patients with Type 2 Diabetes
- 2014
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Ingår i: International Journal of Endocrinology. - : Hindawi Limited. - 1687-8337 .- 1687-8345. ; 2014, s. 323407-
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Tidskriftsartikel (refereegranskat)abstract
- Betatrophin has recently been described as a key hormone to stimulate beta-cell mass expansion in response to insulin resistance and obesity in mice. The finding has generated an interest in the development of antidiabetic drugs with betatrophin as the active component. However, the circulating levels of betatrophin in patients with type 2 diabetes are not well known. Betatrophin concentrations in plasma of 27 type 2 diabetes patients and 18 gender-, age-, and BMI-matched controls were measured. Study participants were characterized with regard to BMI, waist and hip circumference, blood pressure, and fasting plasma blood lipids, creatinine, glucose, HbA1c, and C-peptide. HOMA2 indices were calculated. Betatrophin was 40% higher in patients with type 2 diabetes (893 +/- 80 versus 639 +/- 66 pg/mL). Betatrophin positively correlated with age in the controls and with HbA1c in the type 2 diabetes patients. All study participants were insulin resistant with mean HOMA2B IR in both groups exceeding 2 and HOMA2% S < 50%. Control individuals had impaired fasting glucose concentrations. In this report on betatrophin concentrations in type 2 diabetes and insulin resistance, elevated betatrophin levels were measured in the patients with type 2 diabetes. Future studies are clearly needed to delineate the exact role, if any, of betatrophin in regulating human beta-cell mass.
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| 33. |
- Espes, Daniel, et al.
(författare)
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Increased circulating levels of betatrophin in individuals with long-standing type 1 diabetes
- 2014
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 57:1, s. 50-53
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The hormone betatrophin was recently described as a potent stimulator of beta cell proliferation in mice. Insulin resistance, but not insulin deficiency, caused upregulation of betatrophin expression. If these findings were found to be fully applicable in humans, this would open up the possibility of future betatrophin treatment in type 1 diabetes. The present study measured for the first time betatrophin concentrations in humans and tested the hypothesis that there would be no difference in circulating betatrophin concentrations between patients with type 1 diabetes and healthy individuals. Methods Betatrophin concentrations in plasma of 33 patients with type 1 diabetes and 24 age-matched healthy controls were measured by ELISA. The study participants were characterised for blood lipids, BMI, plasma glucose and HbA(1c), and, for the diabetic patients, their insulin requirements and any residual C-peptide concentrations. Results Plasma betatrophin concentrations were normally similar to 300 pg/ml, but were approximately doubled in patients with type 1 diabetes. In the patients, there were no correlations between betatrophin and age, blood lipids, BMI, glucose control or insulin requirement, whereas in controls betatrophin levels increased with age. BMI, blood pressure and triacylglycerol, LDL-cholesterol and HDL-cholesterol levels were similar in patients and healthy controls. Conclusions/interpretation Circulating concentrations of betatrophin are increased in type 1 diabetes in contrast with what was recently described in an insulin-deficient mouse model. However, increased betatrophin concentrations do not protect against loss of C-peptide. Betatrophin treatment in type 1 diabetes would therefore probably not be successful without the use of supraphysiological doses or a combination with immune regulatory treatment.
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| 34. |
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| 35. |
- Espes, Daniel, et al.
(författare)
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Severe diabetic ketoacidosis in combination with starvation and anorexia nervosa at onset of type 1 diabetes : A case report
- 2013
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 118:2, s. 130-133
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Tidskriftsartikel (refereegranskat)abstract
- We here report a case of diabetic ketoacidosis at onset of type 1 diabetes after a prolonged period of starvation due to anorexia nervosa. A 53-year-old female with a history of anorexia nervosa was admitted to the psychiatric clinic due to psychotic behaviour and inability to take care of herself. Twenty-four hours after admission she was transferred to the clinic of internal medicine due to altered mental status, and laboratory screening revealed a pH of 6.895 and blood glucose concentration of 40 mmol/L. Due to the unusual combination of prolonged starvation and diabetic ketoacidosis we implemented some modifications of existing treatment guidelines and some special considerations regarding nutrition in order to prevent a re-feeding syndrome.
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| 36. |
- Espes, Daniel, et al.
(författare)
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Striated Muscle as Implantation Site for Transplanted Pancreatic Islets
- 2011
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Ingår i: Journal of Transplantation. - : Hindawi Limited. - 2090-0007 .- 2090-0015. ; 2011, s. 352043-
-
Forskningsöversikt (refereegranskat)abstract
- Islet transplantation is an attractive treatment for selected patients with brittle type 1 diabetes. In the clinical setting, intraportal transplantation predominates. However, due to extensive early islet cell death, the quantity of islets needed to restore glucose homeostasis requires in general a minimum of two donors. Moreover, the deterioration of islet function over time results in few insulin-independent patients after five-year followup. Specific obstacles to the success of islet transplantation include site-specific concerns for the liver such as the instant blood mediated inflammatory reaction, islet lipotoxicity, low oxygen tension, and poor revascularization, impediments that have led to the developing interest for alternative implantation sites over recent years. Within preclinical settings, several alternative sites have now been investigated and proven favorable in various aspects. Muscle is considered a very promising site and has physiologically properties and technical advantages that could make it optimal for islet transplantation.
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| 37. |
- Fredriksson, Fanny, et al.
(författare)
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Locally increased concentrations of inflammatory cytokines in an experimental intraabdominal adhesion model
- 2014
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 49:10, s. 1480-1484
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Peritoneal adhesions may cause bowel obstruction, infertility, and pain. This study investigated cytokines, proteins and growth factors thought to promote formation of adhesions in an experimental intraabdominal adhesion model. Methods: Male Sprague-Dawley rats were subjected to laparotomy, cecal abrasion, and construction of a small bowel anastomosis and examined at various time points after surgery. Concentrations of cytokines and growth factors in plasma and peritoneal fluid were analyzed using electrochemoluminescence and quantitative sandwich enzyme immunoassay technique. Results: Concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1 beta), and tumor necrosis factor alpha (TNF-alpha) increased in peritoneal fluid from 6 h after incision. Plasma concentrations of IL-6 increased at 6 h, but plasma concentrations of IL-1 beta and TNF-alpha remained low. Peritoneal fluid concentrations of platelet-derived growth factor-BB (PDGF- BB), transforming growth factor beta1 (TGF-beta 1), vascular endothelial growth factor (VEGF), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were below detection levels at all time points. Conclusion: Early elevations of IL-6, IL-1 beta, and TNF-alpha concentrations in peritoneal fluid correlated to adhesion formation in this rodent model. Our model is relevant and reproducible, suitable for intervention, and indicates that antiadhesion strategies should be early, local and not systemic.
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| 38. |
- Grahn, Pia, 1984-
(författare)
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Electric Vehicle Charging Impact on Load Profile
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- One barrier to sustainable development is considered to be greenhouse gas emissions and pollution caused by transport, why climate targets are set around the globe to reduce these emissions. Electric vehicles (EVs), may be a sustainable alternative to internal combustion engine vehicles since having EVs in the car park creates an opportunity to reduce greenhouse gas emissions. This is due to the efficiency of the electric motor. For EVs with rechargeable batteries the opportunity to reduce emissions is also dependent on the generation mix in the power system. EVs with the possibility to recharge the battery from the power grid are denoted plug-in electric vehicles (PEVs) or plug-inhybrid electric vehicles (PHEVs). Hybrid electric vehicles (HEVs), without external recharging possibility, are not studied, hence the abbreviation EV further covers PHEV and PEV.With an electricity-driven private vehicle fleet, the power system will experience an increased amount of variable electricity consumption that is dependent on the charging patterns of EVs. Depending on the penetration level of EVs and the charging patterns, EV integration creates new quantities in the overall load profile that may increase the load peaks. The charging patterns are stochastic since they are affected by the travel behavior of the driver and the charging opportunities which imply that the EV integration also will have an effect on the load variations. Increased load variation and load peaks may create a need for upgrades in the grid infrastructure to reduce the risk for losses, overloads or damaging of components. However, with well-designed incentives to the EV users the variable electricity consumption due to electric vehicle charging (EVC) may become a flexible load that can help the power system mitigate load variations and load peaks.The aim with this licentiate thesis is to investigate the impact of EVC on load profiles and load variations. The thesis reviews and categorizes EVC models in previous research. The thesis furthermore develops electric vehicle charging models to estimate the charging impact based on charging patterns induced by private car travel behavior. The models mainly consider uncontrolled charging (UCC) related to stochastic individual car travel behavior and induced charging needs for PHEVs. Moreover, the thesis comments on the potential of individual charging strategies (ICS) with flexible charging and external charging strategies (ECS).Three key factors are identified when considering the impact of EVC on load profiles and load variations. The key factors are: The charging moment, the charging need and the charging location. It is concluded that the level of details concerning the approach to model these key factors in EVC models will impact the estimations of the load profiles. This means that models taking into account a higher level of mobility details will be able to create a more realistic estimation of a future UCC behavior, enabling for more accurate estimates of the impact on load profiles and the potential of ICS and ECS.
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| 39. |
- Grahn, Pia, 1984-
(författare)
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Electric Vehicle Charging Modeling
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With an electrified passenger transportation fleet, carbon dioxide emissions could be reduced significantly depending on the electric power production mix. Increased electric power consumption due to electric vehicle charging demands of electric vehicle fleets may be met by increased amount of renewable power production in the electrical systems. With electric vehicle fleets in the transportation system there is a need for establishing an electric vehicle charging infrastructure that distributes this power to the electric vehicles. Depending on the amount of electric vehicles in the system and the charging patterns, electric vehicle integration creates new quantities in the overall load profile that may increase the load peaks. The electric vehicle charging patterns are stochastic since they are affected by the travel behavior of the driver and the charging opportunities which implies that an electric vehicle introduction also will affect load variations. Increased load variation and load peaks may create a need for upgrades in the grid infrastructure to reduce losses, risks for overloads or damaging of components. However, with well-designed incentives for electric vehicle users and electric vehicle charging, the electric vehicles may be used as flexible loads that can help mitigate load variations and load peaks in the power system.The aim with this doctoral thesis is to investigate and quantify the impact of electric vehicle charging on load profiles and load variations. Three key factors are identified when considering the impact of electric vehicle charging on load profiles and load variations. The key factors are: The charging moment, the charging need and the charging location. One of the conclusions in this thesis is that the level of details and the approach to model these key factors impact the estimations of the load profiles. The models that take into account a high level of mobility details will be able to create a realistic estimation of a future uncontrolled charging behavior, enabling for more accurate estimates of the impact on load profiles and the potential of individual charging strategies and external charging strategies. The thesis reviews and categorizes electric vehicle charging models in previous research, and furthermore, introduces new electric vehicle charging models to estimate the charging impact based on charging patterns induced by passenger car travel behavior. The models mainly consider EVC related to individual car travel behavior and induced charging needs for plug-in-hybrid electric vehicles. Moreover, the thesis comments on dynamic electric vehicle charging along electrified roads and also on individual charging strategies.
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| 40. |
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| 41. |
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| 42. |
- Grapensparr, Liza, et al.
(författare)
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The therapeutic role of endothelial progenitor cells in Type 1 diabetes mellitus
- 2011
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Ingår i: Regenerative Medicine. - 1746-0751 .- 1746-076X. ; 6:5, s. 599-605
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Forskningsöversikt (refereegranskat)abstract
- Pancreatic beta-cells sense and adjust the blood glucose level by secretion of insulin. In Type 1 diabetes mellitus, these insulin-producing cells are destroyed, leaving the patients incapable of regulating blood glucose homeostasis. At the time of diagnosis, most patients still have 20-30% of their original beta-cell mass remaining. These residual beta-cells are targets for intervention therapies aimed at preventing further autoimmune destruction, in addition to increasing the number of existing beta-cells. Such a therapeutic option is highly desirable since it may lead to a full recovery of newly diagnosed patients, with no need for further treatment with immunosuppressant drugs or exogenous insulin administration. In this article, we propose that endothelial progenitor cells, a cell type known to promote and support neovascularization following endothelial injury, may be used as part of a combinational stem cell therapy aimed to improve the vascularization, survival and proliferation of beta-cells.
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| 43. |
- Henriksnäs, Johanna, et al.
(författare)
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Markedly Decreased Blood Perfusion of Pancreatic Islets Transplanted Intraportally Into the Liver : Disruption of Islet Integrity Necessary for Islet Revascularization
- 2012
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:3, s. 665-673
-
Tidskriftsartikel (refereegranskat)abstract
- Experimental studies indicate low revascularization of intraportally transplanted islets. This study aimed to quantify, for the first time, the blood perfusion of intrahepatically transplanted islets and elucidate necessary factors for proper islet graft revascularization at this site. Yellow chameleon protein 3.0 islets expressing fluorescent protein in all cells were transplanted. Graft blood perfusion was determined by microspheres. The vascular density and relative contribution of donor blood vessels in revascularization was evaluated using islets expressing green fluorescent protein under the Tie-2 promoter. Blood perfusion of intrahepatic islets was as a mean only 5% of that of native islets at 1-month posttransplantation. However, there was a marked heterogeneity where blood perfusion was less decreased hi islets transplanted without prior culture and in many cases restored in islets with disrupted integrity. Analysis of vascular density showed that distorted islets were well revascularized, whereas islets still intact at 1-month posttransplantation were almost avascular. Few donor endothelial cells were observed in the new islet vasculature. The very low blood perfusion of intraportally transplanted islets is likely to predispose for ischemia and hamper islet function. Since donor endothelial cells do not expand posttransplantation, disruption of islet integrity is necessary for revascularization to occur by recipient blood vessels.
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| 44. |
- Högberg, Niclas, 1979-, et al.
(författare)
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Genes regulating tight junctions and cell adhesion are altered in early experimental necrotizing enterocolitis
- 2013
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 48:11, s. 2308-2312
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Tidskriftsartikel (refereegranskat)abstract
- Background/purpose:Necrotizing enterocolitis (NEC) represents one of the gravest complications in preterm infants and carries significant morbidity and mortality. Increased intestinal permeability may play an important role in the pathogenesis of NEC. In this study we investigated the genes regulating structural proteins such as tight junctions (TJ) and cell adhesion in a neonatal rat model of early NEC, as well as the expression of TJ proteins by immunohistochemistry staining.Methods:The studies were performed on Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation treatment on day 1 after birth. Intestinal specimens from the ileum were obtained, mRNA was purified and the transcriptome was analyzed using microarray. Immunohistochemistry staining was performed for TJ proteins.Results:We found several TJ genes such as claudins 1, 8, 14, 15 and gap junction protein to be affected. Immunohistochemistry staining for TJ protein claudin-1 revealed decreased levels in experimental NEC compared to controls. Alterations in genes involved in the inflammatory response was confirmed, along with several genes regulating proteins used as biomarkers for NEC.Conclusion:This study indicates that tight junctions and cell adhesion may play a critical role in the pathogenesis of early experimental NEC. Better understanding of the pathogenesis of NEC may lead to novel strategies for the prevention and treatment of NEC.
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| 45. |
- Högberg, Niclas, 1979-, et al.
(författare)
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Intestinal ischemia measured by intraluminal microdialysis
- 2012
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 72:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate the possibility of detecting intestinal ischemia by intraluminal microdialysis and comparing the ileum and colon. Methods. The studies were performed on male Sprague-Dawley rats. In the fi rst part of the study, microdialysis catheters were placed in the sigmoid part of the colon and in the subcutaneous adipose tissue. In the second part of the study, microdialysis catheters were placed in the lumen of the ileum and the colon. The infrarenal aorta was clamped proximal to the cranial mesenteric artery. Microdialysate levels of glucose, lactate, pyruvate and glycerol were measured. Intestinal specimens were removed at the end of the ischemic period for microscopic evaluation. Results. Intraluminal microdialysis could detect early signs of ischemic injury in the ileum, as well as in the colon, with a marked increase of lactate, lactate/pyruvate ratio and glycerol. The increased levels of intraluminal glycerol showed a positive correlation to prolonged ischemia and to higher degrees of intestinal damage. Conclusion. Intraluminal measurement of glycerol is a good marker for intestinal ischemia. Intraluminal microdialysis in the colon is easily accessible through the rectum, and ay prove to be a valuable clinical tool for diagnosing intestinal ischemia.
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| 46. |
- Högberg, Niclas, 1979-, et al.
(författare)
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Intraluminal intestinal microdialysis detects markers of hypoxia and cell damage in experimental necrotizing enterocolitis
- 2012
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 47:9, s. 1646-1651
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/PURPOSE:Necrotizing enterocolitis (NEC) represents one of the gravest complications in premature infants and carries significant morbidity and mortality. There is a great need for improved diagnostic methods to reduce the severity and incidence of NEC. The aim of the study was to investigate if intraluminal microdialysis can detect intestinal ischemia in newborn rats with induced experimental NEC.METHODS:The studies were performed on 1-day-old Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation treatment. Microdialysis catheters were rectally inserted and placed in the rectosigmoid part of the colon. Microdialysate levels of glucose, lactate, pyruvate, and glycerol were measured. Intestinal specimens were collected at the end of the experiments for microscopic evaluation.RESULTS:Intraluminal microdialysis revealed signs of intestinal hypoxia and cellular damage, with a marked increase of lactate and glycerol. Microscopic evaluation confirmed intestinal damage in the NEC group.CONCLUSION:Intraluminal microdialysis can detect intestinal hypoxic stress and mucosal cell membrane decay in a rat model of NEC. Intestinal intraluminal microdialysis is easily accessible through the rectum and may be a useful noninvasive complement to other methods in the assessment of NEC.
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| 47. |
- Jansson, Leif, et al.
(författare)
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Flow distribution during infusion of UW and HTK solution in anaesthetised rats
- 2011
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Ingår i: Langenbeck's archives of surgery (Print). - : Springer Science and Business Media LLC. - 1435-2443 .- 1435-2451. ; 396:5, s. 677-683
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Tidskriftsartikel (refereegranskat)abstract
- Organ transplantation necessitates the use of preservation solutions to maintain the integrity of the organs during retrieval. The aim of this study was to investigate the flow distribution in abdominal organs in rats during acute infusion of preservation solution. Microspheres were used to estimate the distribution of flow in the pancreas, duodenum, ileum, colon, liver, kidneys and lungs in untreated Wistar-Furth rats and in animals with an opened abdominal cavity and catheterised aorta. Some animals were infused by free flow of 5 ml of UW, HTK or Ringer solution containing microspheres at a pressure of 100 cm H2O through an intra-aortic catheter. Opening of the abdominal cavity did not affect any of the organ blood flow values. However, the fraction of total pancreatic blood flow diverted through the islets increased. During infusion of microsphere-containing UW, HTK or Ringer solution, splanchnic and renal organ flow values, represented by microsphere contents, were similar. The fraction of microspheres found in the islets was lower in UW-infused rats. The number of microspheres present in the lungs or liver was very low, suggesting that shunting was negligible. Infusion of HTK and UW solution into anaesthetised rats results in a flow distribution which is similar to that in normal animals in most abdominal organs, but there is a reduction in islet blood perfusion by UW but not HTK solution.
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| 48. |
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| 49. |
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| 50. |
- Knutsson, Ola, et al.
(författare)
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Particpatory design of a mobile application for teenagers' language homework
- 2011
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Ingår i: 10th World Conference on Mobile and Contextual Learning.
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Konferensbidrag (refereegranskat)abstract
- In this paper we focus on the design, and in particular the design process of a mobile application for teenagers’ homework in Swedish as a second language. We have used participatory design methods, with the aim to have a userdriven design process. The design process was iterative with several interventions with the students and their teachers. We discuss to what extent the design methods used and applied supports user-driven design. The analysis of the design process showed that it was not to be considered as fully user-driven but it is instead reasonable to consider it as a balanced design process, where the students’ design work was essential for the final product. The application was used in two field tests. The field tests were evaluated using pre- and post questionnaires focusing on the attitudes and opinions of the students using the application for their homework. Results from the questionnaires showed that fully supported mobile learning activities are needed in order to achieve positive attitudes from the students towards using the mobile application for learning Swedish.
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