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  • 1.
    Warth, Benedikt
    Linköping University, The Department of Physics, Chemistry and Biology.
    Design and Application of Software Sensors in Batch and Fed-batch Cultivations during Recombinant Protein Expression in Escherichia coli2008Independent thesis Advanced level (degree of Master), 20 points / 30 hpStudent thesis
    Abstract [en]

    Software sensors are a potent tool to improve biotechnological real time process monitoring and control. In the current project, algorithms for six partly novel, software sensors were established and tested in a microbial reactor system. Eight batch and two fed-batch runs were carried out with a recombinant Escherichia coli to investigate the suitability of the different software sensor models in diverse cultivation stages. Special respect was given to effects on the sensors after recombinant protein expression was initiated by addition of an inducer molecule. It was an objective to figure out influences of excessive recombinant protein expression on the software sensor signals.

    Two of the developed algorithms calculated the biomass on-line and estimated furthermore, the specific growth rate by integration of the biomass changes with the time. The principle of the first was the application of a near infrared probe to obtain on-line readings of the optical density. The other algorithm was founded on the titration of ammonia as only available nitrogen source. The other two sensors analyzed for the specific consumption of glucose and the specific production of acetate and are predicted on an in-line HPLC system.

    The results showed that all software sensors worked as expected and are rather powerful to estimate important state parameters in real time. In some stages, restrictions may occur due to different limitation affects in the models or the physiology of the culture. However, the results were very convincing and suggested the development of further and more advanced software sensor models in the future.

  • 2.
    Bunnfors, Kalle
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Synthesis and electrochemical characterisation of processable polypyrrole boronic acid derivatives for carbohydrate binding2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Conducting polymers have been widely explored for many different purposes including sensing. In thisthesis the conducive properties of pyrrole and the carbohydrate binding properties of boronic acid iscombined to make a reagent-free detector for carbohydrates. The polymer is manufactured in form ofparticles in the μm scale to create a porous film which has a high surface to volume ratio.The material was characterised and the binding properties were evaluated for galactose and glucose.Proof of binding was found via both electrochemical methods and QCM-D. A correlation between R2 value and concentration of substrate was found which enables measurement of concentration of carbohydratesin unknown samples.

  • 3.
    Säberg, Alexander
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Synthesis of a clickable FDG precursor for PET in vivo imaging2015Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    The thesis of this study describes a synthesis way to produce an alkyne equipped clickable precursor of 2-deoxy-2-fluoro-D-glucose (FDG) with a beta-configuration. This FDG-derivate is produced with a clickable link in purpose to be used in PET in vivo imaging. The product was synthesized by acetylation protection and further epoxidation on the glucose analog D-Glucal. Glycosylation occurred by electrophilic reaction of propargyl alcohol and configuration of the product was ensured during Lattrell-Dax inversion.

  • 4.
    Home, P.D.
    et al.
    Newcastle Diabetes Centre, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Pocock, S.J.
    Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom.
    Beck-Nielsen, H.
    Department of Endocrinology and Metabolism, Odense, Denmark.
    Curtis, P.S.
    GlaxoSmithKline Research and Development, Greenford, United Kingdom.
    Gomis, R.
    Hospital Clinic, University of Barcelona, Barcelona, Spain.
    Hanefeld, M.
    Zentrum für Klinische Studien Forschungsbereich Endokrinologie und Stoffwechsel, Dresden, Germany.
    Jones, N.P.
    GlaxoSmithKline Research and Development, Harlow, United Kingdom.
    Komajda, M.
    Université Pierre et Marie Curie Paris 6, Hôpital Pitié-Salpêtrière, Département de Cardiologie, Paris, France.
    McMurray, J.J.
    British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
    Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial2009In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 373, no 9681, 2125-2135 p.Article in journal (Refereed)
    Abstract [en]

    Background: Rosiglitazone is an insulin sensitiser used in combination with metformin, a sulfonylurea, or both, for lowering blood glucose in people with type 2 diabetes. We assessed cardiovascular outcomes after addition of rosiglitazone to either metformin or sulfonylurea compared with the combination of the two over 5-7 years of follow-up. We also assessed comparative safety. Methods: In a multicentre, open-label trial, 4447 patients with type 2 diabetes on metformin or sulfonylurea monotherapy with mean haemoglobin A 1c (HbA 1c) of 7·9% were randomly assigned to addition of rosiglitazone (n=2220) or to a combination of metformin and sulfonylurea (active control group, n=2227). The primary endpoint was cardiovascular hospitalisation or cardiovascular death, with a hazard ratio (HR) non-inferiority margin of 1·20. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00379769. Findings: 321 people in the rosiglitazone group and 323 in the active control group experienced the primary outcome during a mean 5·5-year follow-up, meeting the criterion of non-inferiority (HR 0·99, 95% CI 0·85-1·16). HR was 0·84 (0·59-1·18) for cardiovascular death, 1·14 (0·80-1·63) for myocardial infarction, and 0·72 (0·49-1·06) for stroke. Heart failure causing admission to hospital or death occurred in 61 people in the rosiglitazone group and 29 in the active control group (HR 2·10, 1·35-3·27, risk difference per 1000 person-years 2·6, 1·1-4·1). Upper and distal lower limb fracture rates were increased mainly in women randomly assigned to rosiglitazone. Mean HbA 1c was lower in the rosiglitazone group than in the control group at 5 years. Interpretation: Addition of rosiglitazone to glucose-lowering therapy in people with type 2 diabetes is confirmed to increase the risk of heart failure and of some fractures, mainly in women. Although the data are inconclusive about any possible effect on myocardial infarction, rosiglitazone does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs. Funding: GlaxoSmithKline plc, UK. © 2009 Elsevier Ltd. All rights reserved.

  • 5.
    Rehman, Atif ur
    et al.
    Biosciences, School of Life and Medical Sciences, University of Hertfordshire, College, United Kingdom.
    Dugic, Elma
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Benham, Chris
    Biosciences, School of Life and Medical Sciences, University of Hertfordshire, College, United Kingdom.
    Lione, Lisa
    Biosciences, School of Life and Medical Sciences, University of Hertfordshire, College, United Kingdom.
    Mackenzie, Louise S
    Biosciences, School of Life and Medical Sciences, University of Hertfordshire, College, United Kingdom.
    Selective inhibition of NADPH oxidase reverses the over contraction of diabetic rat aorta2014In: Redox Biology, ISSN 2213-2317, Vol. 2, no 1, 61-64 p.Article in journal (Refereed)
    Abstract [en]

    Abnormal vascular responsiveness in diabetes has been attributed to a number of changes in contractile pathways, affected in part by the overproduction of reactive oxygen species (ROS). It has been reported that NADPH oxidase (NOX) is increased in diabetic (streptozotocin treated; STZ) rat arteries; however the pharmacological agents used to inhibit NOX activity are known to be unsuitable for in vitro studies and have a high level of non-selectivity. Here we have used the highly selective NOX inhibitor VAS2870 in diabetic rat aorta and compared its effects with apocynin, SOD, and allopurinol on phenylephrine and U46619 induced contraction. Male Wistar rats were injected intraperitoneally with 65mg/kg STZ and development of diabetes was confirmed by testing blood glucose levels. Rats were killed by CO2 asphyxiation, and the thoracic aorta removed and mounted in an organ bath under a tension of 1g. Diabetic rat aortas exhibit a greatly increased response to phenylephrine, which was reduced to a level consistent with control rat aorta by 10-5M VAS2870 and 150U/ml SOD. Incubation with VAS2870 led to an increase in normal rat aorta contraction, but led to a significant reduction in phenylephrine and U46619 induced tone in diabetic rat aorta, which indicates that ROS in diabetic rats directly contributes to these contractile responses. Apocynin and allopurinol had no effect on contraction in diabetic or normal rat aorta. This data is the first to show that selective inhibition of NOX reduces diabetic arterial contraction in direct comparison with inhibition of other known contributors of ROS.

  • 6.
    Willén, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
    Synthesis of azidoethyl 3,4,6-tri-O-acetyl-α-D-mannopyranoside for future bioconjugation in PET studies2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Positron emission tomography is a powerful imaging method capable of diagnosing and studyingdiseases at atomic levels. The following thesis involves the synthesis of a 2 -deoxy-2 -[18F]uoro-D-glucose derivative able to participate in click chemisty conjugation. The synthesis involves six stepswith D-mannopyranose as starting material; regioselective acetylation and protection of the hydroxylgroup on C-2 of the monosaccharide, glycosylation with 2-azidoethanol, removal of the selectiveprotecting group and substitution of the hydroxyl group on C-2 with uorine. The potential toconjugate the glycoside to other biomolecules and obtain PET data might have uses in diagnosticaland medicinal chemistry.

  • 7.
    Tiwari, Ashutosh
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics.
    DEVELOPMENT OF AMPEROMETRIC GLUCOSE BIOSENSOR BASED ON NANOWIRE-NANORIBBON JUNCTION ARRAYS OF ZNO2013Conference paper (Refereed)
  • 8.
    Dahlfors, Gunilla
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans J.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Expression of insulin-like growth factor binding proteins and transforming growth factor-ß1 in human microvascular endothelial and bovine aortic endothelial cells, no effects of high glucoseManuscript (preprint) (Other academic)
    Abstract [en]

    Vascular complications are the major cause of morbidity and mortality in patients with diabetes mellitus. Insnlin-like growth factor-I (IGF-I) and transforming growth factor-ß1 (TGF-ß1) are two growth factors that regnlate vascular smooth muscle cell function in vivo and might be involved in the development of diabetic vascnlar complications. In this study we measnred the expression of IGF-binding proteins (IGFBPs) and TGF-ß1 in human dermal microvessel endothelial cells (HDMEC). We also studied the effect of high glucose levels on the expression of IGFBPs and TGF-ß1 in cnltured HDMEC and bovine aortic endothelial cells (BAEC). Gene expression was measured by an RNase-protection assay and proteins secreted into conditioned medium by ELISA or Western blot. The HDMEC expressed mRNAs for IGF-I and IGFBP-2 through -6 of which IGFBP-4 was the most excessively expressed and IGFBP-2 and -4 were detected in conditioned medium. Culture of HDMEC in high glucose (25 mM) for two passages did not change mRNA expressions for IGFBP-2, -3 or -4 significantly. Neither did low glucose+ mannitol (5.6 mM+ 20 mM) have any effect. In BAEC, high glucose (25 mM) for 48 h or 96 h did not affect IGFBP-3, -4 or -5 mRNA or protein and exposnre of BAEC to high glucose for two passages did also not affect IGFBP mRNA. TGF-ß1 mRNA was expressed by both BAEC and HDMEC. High glucose for two passages did not alter TGF-ß1 gene expression in either BAEC or HDMEC. In conclusion, we show that HDMEC express IGFBPs and TGF-ß1 andthat high glucose does not affect the expression in either HDMEC or BAEC.

  • 9.
    Höckerdal, Henrik
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, The Institute of Technology.
    Electrochemical Measurements of Salivary Amylase Activity2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Stress constitutes a more and more common cause for many health disorders inmodern society. Salivary -amylase (AA), the most abundant enzyme in humanwhole saliva, has in recent years been found to be a good surrogate biomarker formonitoring stress levels in individuals. This work aims to form the foundation ofa novel approach for measuring the activity of the enzyme in saliva samples bymeans of electrochemistry. The idea is to implement several enzymes along witha starch substrate and an electron mediator in a single system. This system isthen to be coated onto a screen-printed electrode (SPE), which is used along withan electrical component, designed to give rise to a quantifiable, electrical signalwhen the starch is broken down by the AA contained in an added saliva sample.Several such enzyme systems are here qualitatively evaluated. As electron mediator,ferro-/ferricyanide is used. Two different enzymes, glucose oxidase (GOx) andpyrroloquinoline quinone dependent glucose dehydrogenase (PQQ-GDH), are testedfor making up the saccharide oxidising part of the system. Both prove themselvescapable in terms of qualitatively giving rise to an electrical signal. But, in terms ofinternal quantitative comparisons between the two, no practical experiments areperformed in this work. In some runs, the enzyme -glucosidase (AG) is used asan intermediate for breaking down the AA/starch oligosaccharide products intomonosaccharides. This to increase the system’s electrical signal output when usingGOx as oxidising agent. Regrettably, due to lack of AG enzyme, these runs do notprovide any conclusive data, and so further investigations of systems including thisenzyme are needed. Otherwise, all systems tested seem to work, and neither ofthem appear better than the others. Therefore, all of them will require furtherquantitative testing to determine which one is best to implement in the final designof the enzyme system to be applied onto the SPE.

  • 10.
    Vanichbuncha, Tita
    Linköping University, Department of Computer and Information Science, Statistics. Linköping University, The Institute of Technology.
    Risk Factors and Predictive Modeling for Aortic Aneurysm2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In 1963 – 1965, a large-scale health screening survey was undertaken in Sweden and this data set was linked to data from the national cause of death register. The data set involved more than 60,000 participants whose age at death less than 80 years. During the follow-up period until 2007, a total of 437 (338 males and 99 females) participants died from aortic aneurysm. The survival analysis, continuation ratio model, and logistic regression were applied in order to identify significant risk factors. The Cox regression after stratification for AGE revealed that SEX, Blood Diastolic Pressure (BDP), and Beta-lipoprotein (BLP) were the most significant risk factors, followed by Cholesterol (KOL), Sialic Acid (SIA), height, Glutamic Oxalactic Transaminase, Urinary glucose (URIN_SOC), and Blood Systolic Pressure (BSP). Moreover, SEX and BDP were found as risk factors in almost every age group. Furthermore, BDP was strongly significant in both male and female subgroup.

     

    The data set was divided into two sets: 70 percent for the training set and 30 percent for the test set in order to find the best technique for predicting aortic aneurysm. Five techniques were implemented: the Cox regression, the continuation ratio model, the logistic regression, the back-propagated artificial neural network, and the decision tree. The performance of each technique was evaluated by using area under the receiver operating characteristic curve. In our study, the continuation ratio and the logistic regression outperformed among the other techniques.

  • 11.
    Axelsson, Josefin
    Linköping University, Department of Physics, Chemistry and Biology.
    Separate Hydrolysis and Fermentation of Pretreated Spruce2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Bioethanol from lignocellulose is expected to be the most likely fuel alternative in the near future. SEKAB E-Technology in Örnsköldsvik, Sweden develops the technology of the 2nd generation ethanol production; to produce ethanol from lignocellulosic raw material. The objective of this master’s thesis was to achieve a better knowledge of the potential and limitations of separate hydrolysis and fermentation (SHF) as a process concept for the 2nd generation ethanol production. The effects of enzyme concentration, temperature and pH on the glucose concentration in the enzymatic hydrolysis were investigated for pretreated spruce at 10% DM using a multiple factor design. Enzyme concentration and temperature showed significant effects on the glucose concentration, while pH had no significant effect on the concentration in the tested interval of pH 4.5-5.5. To obtain the maximum glucose concentration (46.4 g/l) for a residence time of 48 h, the optimal settings within the studied parameter window are a temperature of 45.7⁰C and enzyme concentration of 15 FPU/g substrate. However, a higher enzyme concentration would probably further increase the glucose concentration. If enzymatic hydrolysis should be performed for very short residence times, e.g. 6 h, the temperature should be 48.1⁰C to obtain maximum glucose concentration. The efficiency of the enzymes was inhibited when additional glucose was supplied to the slurry prior to enzymatic hydrolysis. It could be concluded that end product inhibition by glucose occurs and results in a distinct decrease in glucose conversion. No clear conclusions could be drawn according to different techniques for slurry and enzymes, i.e. batch and fed-batch, in the enzymatic hydrolysis process. Investigations of the fermentability of the hydrolysate revealed that the fermentation step in SHF is problematic. Inhibition of the yeast decrease the fermentation efficiency and it is therefore difficult to achieve the 4% ethanol limit. Residence time for enzymatic hydrolysis (48 h) and fermentation (24 h) need to be prolonged to achieve a sufficient SHF process. However, short processing times are a key parameter to an economically viable industrial process and to prolong the residence times should therefore not be seen as a desirable alternative. SHF as a process alternative in an industrial bioethanol plant has both potential and limitations. The main advantage is the possibility to separately optimize the process steps, especially to be able to run the enzymatic hydrolysis at an optimal temperature. Although, it is important to include all the process steps in the optimization work. The fermentation difficulties together with the end product inhibition are two limitations of the SHF process that have to be improved before SHF is a preferable alternative in a large scale bioethanol plant. 

  • 12.
    Gustavsson, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology .
    On-line control of glucose feeding in an Escherichia coli fed-batch cultivation expressing a recombinant protein.2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Soft sensors have been suggested as potent tools for on-line estimations of critical bioprocess variables to be able to control the biological process in an as high extent as possible. The formation of inhibitory by-products in the form of organic acids, caused by an overflow of glucose, is a problem in most bioprocesses expressing recombinant proteins. 

     

    In this project a new method of controlling the glucose feeding in an Escherichia coli fed-batch cultivation expressing the green fluorescent protein (GFP) was investigated. The new controller system implemented in the software controlled the feed rate based on on-line HPLC measurements of the concentration of organic acids.   

     

    The results showed that the controller managed to down-regulate the inhibitory organic acids to a low level as it tried to keep the glucose uptake rate at an optimum for maximum cell growth. The results suggested that the controller could be a powerful tool to create a more secure reproducibility and to generate high product yields in recombinant protein productions.   

  • 13.
    Palmqvist, Emma
    Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Mutagenesis of the sugar donor site of the Arabidopsis thaliana glycosyltransferase UGT72B12010Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The Arabidopsis thaliana glycosyltransferase UGT72B1 is one of many enzymes which catalyze the reaction oflinking a glucose moiety from UDP-glucose to an acceptor molecule, in this case a chloroaniline or a chlorophenol. This is part of a detoxification system of the plant cell, similar to that in humans where a glucuronosyltransferases are enabling drug metabolism. It would be of interest to investigate the activity of the human enzyme towards different pharmaceuticals and determine the effect the linkage of glucose has to properties of the compounds. However, the human enzymes are membrane proteins and thus difficult to purify and crystallize. Here, an attempt was made to instead change the substrate specificity of UGT72B1 from UDPglucose to UDP-glucuronic acid. Combination of the four point mutations G18S, P139R, W367S and AG387ED were introduced in UGT72B1. However, no UDP-glucuronic acid activity was obtained. Single mutants W367S and AG387ED retained similar activity as of the wildtype while P139R had highly reduced activity and G18S was not expressed at all. All other combinations of mutations resulted in even less activity. Four chimeric proteins were also constructed. They were combinations of the UGT72B1 and the human enzyme UGT2B4. These were all soluble proteins but no activity could be determined.

  • 14.
    Johansson, Linda
    Linköping University, The Tema Institute, Department of Water and Environmental Studies.
    Temperature sensitivity of decomposition in a boreal mixed mire in northern Sweden2010Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Carbon accumulation in soils constitutes a significant sink for carbon. How the climate change with increasing temperatures will affect the soil carbon storage represents uncertainty of the predictions in the climate change ecosystem feedback mechanisms. In this study the temperature impact on the decomposition of the large carbon pools in peatlands was investigated. Peat cores from different microtopographic units in a boreal oligotrophic minerogenic mire in northern Sweden were collected from in three depths (5-10, 10-15 and 15-20 centimeters below the surface). The samples were incubated at four temperatures: 4, 9, 14 and 19°C and the heterotrophic respiration (CO2- production) was measured hourly or 37 days. Unexpectedly, basal respiration did not show any correlation with temperature. However, the exponential increase in respiration (µ) was correlated with temperature: i.e.  giving Q10 values between 2 (SE +/- 0.36) and 5 (SE +/-1.05). Soil depth or vegetation covers did not affect temperature response (Q10) of µ. The substrate induced respiration (SIR) did not occour but for a few of the samples.

    The conclusion from this study is that degradation of peat seams not be affected by a temperature increase. The addition of glucose, nitrogen and phosphorus increased with increasing temperature with a Q10 value as expected.

  • 15.
    Sohlstrom, A
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Carlsson, C
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Uvnas-Moberg, K
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Effects of oxytocin treatment in early life on body weight and corticosterone in adult offspring from ad libitum-fed and food-restricted rats2000In: Biology of the Neonate, ISSN 0006-3126, Vol. 78, no 1, 33-40 p.Article in journal (Refereed)
    Abstract [en]

    The aims of this study were: (1) to assess the effects of maternal undernutrition during pregnancy on adult offspring with regard to growth, body composition and plasma levels of glucose, insulin and corticosterone, and (2) to investigate whether oxytocin treatment early in life could ameliorate the adverse effects of food restriction in utero. Pups from ad libitum-fed and food-restricted (60% of ad libitum intake during pregnancy) rats were injected subcutaneously once a day with oxytocin or saline on days 1-14 after birth. At adult age (62 days), male offspring from food-restricted darns had lower body weight, less adipose tissue, lower plasma glucose but higher corticosterone levels, compared to offspring from ad libitum-fed dams. However, oxytocin-treated food-restricted males had higher body weight, higher glucose and lower corticosterone levels compared to their saline-treated counterparts. In conclusion, oxytocin treatment early in life seems to ameliorate some of the adverse effects of food restriction in utero. Copyright (C) 2000 S. Karger AG, Basel.

  • 16. Tkac, J.
    et al.
    Vostiar, I.
    Department of Biochemical Technology, Fac. of Chemical and Food Technology, Slovak University of Technology, Radlinskeho 9, SK-812 37 Bratislava, Slovakia.
    Gorton, L.
    Department of Analytical Chemistry, Lund University, PO Box 124, SE-22 100 Lund, Sweden.
    Gemeiner, P.
    Institute of Chemistry, Slovak Academy of Sciences, Dubravska cesta 9, SK-842 38 Bratislava, Slovakia.
    Sturdik, E.
    Department of Biochemical Technology, Fac. of Chemical and Food Technology, Slovak University of Technology, Radlinskeho 9, SK-812 37 Bratislava, Slovakia.
    Improved selectivity of microbial biosensor using membrane coating. Application to the analysis of ethanol during fermentation2003In: Biosensors & bioelectronics, ISSN 0956-5663, Vol. 18, no 9, 1125-1134 p.Article in journal (Refereed)
    Abstract [en]

    A ferricyanide mediated microbial biosensor for ethanol detection was prepared by surface modification of a glassy carbon electrode. The selectivity of the whole Gluconobacter oxydans cell biosensor for ethanol determination was greatly enhanced by the size exclusion effect of a cellulose acetate (CA) membrane. The use of a CA membrane increased the ethanol to glucose sensitivity ratio by a factor of 58.2 and even the ethanol to glycerol sensitivity ratio by a factor of 7.5 compared with the use of a dialysis membrane. The biosensor provides rapid and sensitive detection of ethanol with a limit of detection of 0.85 µM (S/N=3). The selectivity of the biosensor toward alcohols was better compared to previously published enzyme biosensors based on alcohol oxidase or alcohol dehydrogenases. The biosensor was successfully used in an off-line monitoring of ethanol during batch fermentation by immobilized Saccharomyces cerevisiae cells with an initial glucose concentration of 200 g l-1. © 2002 Elsevier Science B.V. All rights reserved.

  • 17.
    Graneli, W.
    et al.
    Department of Ecology, Limnology, Ecol. Bldg., SE-223 62 Lund, Sweden.
    Carlsson, P.
    Department of Marine Sciences, Kalmar University, P.O. Box 905, SE-391 29 Kalmar, S..
    Bertilsson, S.
    Linköping University, The Tema Institute, Department of Water and Environmental Studies. Linköping University, Faculty of Arts and Sciences.
    Bacterial abundance, production and organic carbon limitation in the Southern Ocean (39-62°S, 4-14°E) during the austral summer 1997/19982004In: Deep-sea research. Part II, Topical studies in oceanography, ISSN 0967-0645, Vol. 51, no 22-24, 2569-2582 p.Article in journal (Refereed)
    Abstract [en]

    Bacterial abundance and production were studied in different zones in the Southern Ocean (39-62°S, 4-14°E) during a cruise in December-January 1997/1998. The role of potential growth limitation of bacteria due to limited availability of organic carbon (glucose) or inorganic N and P was studied in parallel. A positive correlation between surface water temperatures (-2 to 18°C) and bacterial abundance (

  • 18. Ronquist, G
    et al.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Inherited, non-spherocytic haemolysis due to deficiency of glucose-6-phosphate dehydrogenase2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, Vol. 67, no 1, 105-111 p.Article in journal (Refereed)
    Abstract [en]

    The about 400 million individuals worldwide suffering from a hereditary deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD) may experience different degrees of haemolytic anaemia. Haemoglobin is present in very high concentrations in the erythrocyte cytoplasm, at risk of falling out of solution if the internal environment or the haemoglobin itself is changed. G6PD is a crucial enzyme producing reduced glutathione in the erythrocyte cytoplasm for the purpose of protecting haemoglobin against oxidative damage. The presence of unopposed oxidizing agents leading to oxidation of the sulfhydryl bridges between parts of the haemoglobin molecule decrease the solubility of haemoglobin, leading to precipitations called Heinz bodies. The laboratory investigation of G6PD deficiency is commonly done by a quantitative spectrophotometric analysis or by a rapid fluorescent spot test detecting the generation of NADPH from NADP. Genetic tests based on polymerase chain reaction detect specific mutations and may be used for population screening, family studies, or prenatal diagnosis. © 2007 Taylor & Francis.

  • 19.
    Lisander, Björn
    et al.
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Lundvall, Olle
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Tomner, Jens
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences.
    Jones, A Wayne
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Enhanced rate of ethanol elimination from blood after intravenous administration of amino acids compared with equicaloric glucose2006In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 41, no 1, 39-43 p.Article in journal (Refereed)
    Abstract [en]

    Aims: To investigate the effect of an amino acid mixture given intravenously (i.v.) on the rate of ethanol elimination from blood compared with equicaloric glucose and Ringer's acetate as control treatments.

    Methods: In a randomized cross-over study, six healthy men (mean age 23 years) fasted overnight before receiving either Ringer's acetate, glucose or the amino acid mixture (Vamin 18 g N/l®) by constant rate i.v. infusion over 4.5 h. Ethanol (0.4 g/kg) was given by an i.v. infusion lasting 60 min during the time each of the treatments was administered. At various times post-infusion, blood samples were taken for determination of ethanol by headspace gas chromatography. Blood glucose and heart rate were monitored at regular intervals. Concentration–time profiles of ethanol were plotted for each subject and the rate of ethanol disappearance from blood as well as other pharmacokinetic parameters were compared by repeated measures analysis of variance.

    Results: The rate of ethanol elimination from blood was increased significantly (P < 0.001) after treatment with amino acids (mean ± SD, 0.174 ± 0.011 g/l/h) compared with equicaloric glucose (0.121 ± 0.016 g/l/h) or Ringer's acetate (0.110 ± 0.013 g/l/h). Heart rate was also slightly higher during infusion of the amino acid mixture (P < 0.05).

    Conclusions: When the rate of ethanol elimination from blood is relatively slow, such as after an overnight fast, it can be increased by ∼60% after treatment with i.v. amino acids. The efficacy of amino acid treatment was not related to the supply of calories because glucose was no more effective than Ringer's acetate. We suggest that amino acids might increase hepatic oxygen consumption, resulting in a more effective conversion of NADH to NAD+ in mitochondria. An important feature of the experimental design was ensuring hepatic availability of amino acids during much of the time that ethanol was being metabolized.

  • 20.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Urine as a biological specimen for forensic analysis of alcohol and variability in the urine-to-blood relationship2006In: Toxicological Reviews, ISSN 1176-2551, Vol. 25, no 1, 15-35 p.Article in journal (Refereed)
    Abstract [en]

    This article concerns the use of urine as a biological specimen for determination of alcohol in clinical and forensic toxicology and discusses factors that might influence variability in the urine/blood concentration ratio of alcohol. A large number of human drinking experiments were conducted to determine the time course of urine-alcohol concentrations (UAC) in relation to blood-alcohol concentrations (BAC). The UAC and BAC curves were shifted in time and the BAC curve always began to decrease before the UAC started to decline. During the early absorption phase the UAC/BAC ratio was less than unity, whereas in the late absorption/ distribution period the ratio was between 1.0-1.2. On reaching the post-absorptive phase, the UAC always exceeded BAC and UAC/BAC ratios averaged 1.3-1.4, increasing appreciably as BAC decreased towards zero. Alcohol-induced diuresis was most pronounced during the rising portion of the BAC curve and near to the peak value. After about 2 hours post-drinking, the production rate of urine diminished to the pre-drinking rate of about 0.5-1 mL/min. Drinking water during the post-absorptive phase of the alcohol curve produced dilute urine, as reflected in lower creatinine content and osmolality, although the concentration of ethanol remained unchanged. After subjects drank a moderate dose of ethanol (0.54-0.85 g/kg) about 2% of the dose was recoverable in the urine after 7 hours. Ethyl glucuronide, a minor metabolite of ethanol, was measured in urine samples from drunk drivers. The UAC/BAC ratio of ethanol in drunk drivers did not depend on the creatinine content of the urine and therefore the relative dilution of the specimens. When alcohol-free urine was spiked with glucose and infected with the yeast species Candida albicans, ethanol was produced by fermentation after approximately 24 hours storage at room temperature. This post-sampling synthesis of ethanol was prevented by sodium fluoride (1% weight by volume) in the urine tubes or by keeping the specimens in the cold (4°C). The UAC and BAC were highly correlated (r > 0.95) in drunk drivers and in autopsy cases, although the residual standard deviations were appreciable. This speaks against attempting to estimate BAC indirectly from UAC in any individual case. The UAC/BAC ratio and the change in UAC between two successive voids can help to resolve whether a large amount of alcohol had recently been consumed. This information is useful to support or challenge allegations of drinking alcohol after driving, which has become known as the hip-flask defence.

  • 21.
    Samuelsson, Anders
    et al.
    Linköping University, Department of Medicine and Care, Anaesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Sjöberg, Folke
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Microdialysis shows metabolic effects in skin during fluid resuscitation in burn-injured patients2006In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 10, no 6, Art.no: R172- p.Article in journal (Refereed)
    Abstract [en]

    Introduction: Established fluid treatment formulas for burn injuries have been challenged as studies have shown the presence of tissue hypoxia during standard resuscitation. Such findings suggest monitoring at the tissue level. This study was performed in patients with major burn injuries to evaluate the microdialysis technique for the continuous assessment of skin metabolic changes during fluid resuscitation and up to four days postburn. Methods: We conducted an experimental study in patients with a burn injury, as represented by percentage of total body surface area burned (TBSA), of more than 25% in a university eight-bed burns intensive care unit serving about 3.5 million inhabitants. Six patients with a median TBSA percentage of 59% (range 33.5% to 90%) and nine healthy controls were examined by intracutaneous MD, in which recordings of glucose, pyruvate, lactate, glycerol, and urea were performed. Results: Blood glucose concentration peaked on day two at 9.8 mmol/l (6.8 to 14.0) (median and range) and gradually declined on days three and four, whereas skin glucose in MD continued to increase throughout the study period with maximum values on day four, 8.7 mmol/l (4.9 to 11.0). Controls had significantly lower skin glucose values compared with burn patients, 3.1 mmol/l (1.5 to 4.6) (p < 0.001). Lactate from burn patients was significantly higher than controls in both injured and uninjured skin (MD), 4.6 mmol/l (1.3 to 8.9) and 3.8 mmol/l (1.6 to 7.5), respectively (p < 0.01). The skin lactate/pyruvate ratio (MD) was significantly increased in burn patients on all days (p < 0.001). Skin glycerol (MD) was significantly increased at days three and four in burn patients compared with controls (p < 0.01). Conclusion: Despite a strategy that fulfilled conventional goals for resuscitation, there were increased lactate/pyruvate ratios, indicative of local acidosis. A corresponding finding was not recorded systemically. We conclude that MD is a promising tool for depicting local metabolic processes that are not fully appreciated when examined systemically. Because the local response in glucose, lactate, and pyruvate metabolism seems to differ from that recorded systemically, this technique may offer a new method of monitoring organs. © 2006 Samuelsson et al., licensee BioMed Central Ltd.

  • 22.
    Theodorsson, Elvar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Birgens, H
    Hagve, TA
    Haemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency in a Scandinavian perspective2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, Vol. 67, no 1Article in journal (Refereed)
    Abstract [en]

    Haemoglobinopathies (mainly thalassaemia and sickle-cell anaemia syndromes) and glucose-6-phosphate dehydrogenase deficiency (G6PD) are globally among the most prevalent single-genomic diseases. About 3 % of the world's population are heterozygotic for β-thalassaemia and about 1-2 % for sickle-cell anaemia, and it is estimated that more than 400 million people are affected by G6PD deficiency worldwide. The disorders are most prevalent in the Mediterranean area, in Asia and Africa. The Scandinavian countries, among others, have seen a boom in immigration during the past 20 years, and therefore migration makes haemoglobinopathies as well as G6PD deficiency increasingly more important from a differential diagnostic perspective in most countries. The purpose of the present special issue of the Journal is to summarize current epidemiological data and elucidate trends and practices in the laboratory diagnosis of these disorders. © 2007 Taylor & Francis.

  • 23. Robertson, KJ
    et al.
    Schoenle, E
    Gucev, Z
    Mordhorst, L
    Gall, MA
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Insulin detemir compared with NPH insulin in children and adolescents with Type 1 diabetes2007In: Diabetic Medicine, ISSN 0742-3071, Vol. 24, no 1, 27-34 p.Article in journal (Refereed)
    Abstract [en]

    Aims: This study compared the effect of insulin detemir on glycaemic control (HbA1c, fasting plasma glucose and variability thereof) with that of Neutral Protamine Hagedorn human isophane (NPH) insulin, both combined with insulin aspart, in children with Type 1 diabetes mellitus, and compared the safety of these treatments. Methods: In this 26-week, open-label, randomized (2 : 1), parallel-group study, 347 (140 prepubertal and 207 pubertal) children with Type 1 diabetes, aged 6-17 years, received insulin detemir (n = 232) or NPH insulin (n = 115) once or twice daily, according to the prestudy regimen, plus premeal insulin aspart. Results: The mean HbA1c decreased by ∼0.8% with both treatments. After 26 weeks, the mean difference in HbA 1c was 0.1% (95% confidence interval -0.1, 0.3) (insulin detemir 8.0%, NPH insulin 7.9%). Within-subject variation in self-measured fasting plasma glucose was significantly lower with insulin detemir than with NPH insulin (SD 3.3 vs. 4.3, P < 0.001), as was mean fasting plasma glucose (8.4 vs. 9.6 mmol/l, P = 0.022). The risk of nocturnal hypoglycaemia (22.00-07.00 h) was 26% lower with insulin detemir (P = 0.041) and the risk of 24-h hypoglycaemia was similar with the two treatments (P = 0.351). The mean body mass index (BMI) Z-score was lower with insulin detemir (P < 0.001). Conclusions: Basal-bolus treatment with insulin detemir or NPH insulin and premeal insulin aspart in children and adolescents with Type 1 diabetes mellitus improved HbA1c to a similar degree. The lower and more predictable fasting plasma glucose, lower risk of nocturnal hypoglycaemia and lower BMI observed with insulin detemir are clinically significant advantages compared with NPH insulin. © 2007 The Authors.

  • 24.
    Svedjeholm, Rolf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Insulin-Glucose and cardiac function. Abstract Post Graduate Course Session III - Next steps to ameliorate perfusion2006In: 5th EACTS/ESTS Joint meeting,2006, Stockholm: Stockholm , 2006, 88- p.Conference paper (Refereed)
    Abstract [en]

        

  • 25.
    Hillman, Jan
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Milos, Peter
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Zhengquan, Yu
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Sjögren, Florence
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Mellergård, Pekka
    Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Intracerebral microdialysis in neurosurgical intensive care patients utilising catheters with different molecular cut-off (20 and 100 kD)2006In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 148, no 3, 319-324 p.Article in journal (Refereed)
    Abstract [en]

    Objective. To compare the properties of a new intracerebral micro-dialysis catheter with a high cut-off membrane (molecular cut-off 100 kDalton) with a standard catheter (CMA70, molecular cut-off 20 kDalton).

    Methods. Paired intracerebral microdialysis catheters were inserted in fifteen comatose patients treated in a neurosurgical intensive care unit following subarachnoid haemorrhage or traumatic brain injury. The high-cut-off catheter (D100) differed from the CMA 70 catheter by the length (20 mm) and cut-off properties of the catheter membranes (100 kDalton) and the perfusion fluids used (Ringer-Dextran 60). Samples were collected every 4–6 hours, analyzed bedside (for glucose, glutamate, glycerol, lactate, pyruvate and urea) and later in the laboratory (for total protein).

    Results. Fluid recovery was similar for the two types of catheters, but significantly more protein was recovered by the D100 catheter. The recovery of glycerol and pyruvate did not differ, while minor differences in recovery of glutamate and glucose were observed. The recovery of lactate was considerably lower in the D100 catheter (p < 0.01), influencing the lactate/pyruvate-ratio. The patterns of concentration changes over time were consistent for all metabolites, and independent of type of catheter.

    Conclusion. Microdialysis catheters with high cut-off membranes can be used in routine clinical practice in the NSICU, adding the possibility of macro-molecule sampling from the extracellular space during monitoring.

  • 26. Prytz, Hanne
    et al.
    Keiding, Susanne
    Björnsson, Einar
    Broomé, Ulrika
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Castedal, Maria
    Lajord Munk, Ole
    Dynamic FDG-PET is useful for detection of cholangiocarcinoma in patients with PSC listed for liver transplantation2006In: Hepatology, ISSN 0270-9139, Vol. 44, no 6, 1572-1580 p.Article in journal (Refereed)
    Abstract [en]

    Five to 15% of patients with primary sclerosing cholangitis (PSC) develop cholangiocarcinoma (CC) with a median survival of 5 to 7 months, an outcome not significantly improved by liver transplantation. However, if CC is found incidentally during the procedure or in the explanted liver, 5-year survival rates of 35% are reported. A noninvasive method to detect CC small enough to allow for intended curative surgery is needed. Unfortunately, computed tomography (CT) and ultrasonography (US) have poor sensitivity for detection of CC in PSC, however, positron emission tomography (PET) using 2-[ 18F]fluoro-2-deoxy-D-glucose (FDG) differentiates well between CC and nonmalignant tissue. We examined whether PET findings are valid using a blinded study design comparing pretransplantation FDG-PET results with histology of explanted livers. Dynamic FDG-PET was performed in 24 consecutive patients with PSC within 2 weeks after listing for liver transplantation and with no evidence of malignancy on CT, magnetic resonance imaging, or ultrasonography. The PET Center staff was blinded to clinical findings, and surgeons and pathologists were blinded to the PET results. Three patients had CC that was correctly identified by PET. PET was negative in 1 patient with high-grade hilar duct dysplasia. In 20 patients without malignancies, PET was false positive in 1 patient with epitheloid granulomas in the liver. In conclusion, dynamic FDG-PET appears superior to conventional imaging techniques for both detection and exclusion of CC in advanced PSC. FDG-PET may be useful for screening for CC in the pretransplant evaluation of patients with PSC. Copyright © 2006 by the American Association for the Study of Liver Diseases.

  • 27.
    Örtegren Kugelberg, Unn
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Yin, Lan
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Öst, Anita
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Separation and characterization of caveolae subclasses in the plasma membrane of primary adipocytes: segregation of specific proteins and functions2006In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 273, no 14, 3381-3392 p.Article in journal (Refereed)
    Abstract [en]

    Caveolae are nearly ubiquitous plasma membrane domains that in adipocytes vary in size between 25 and 150 nm. They constitute sites of entry into the cell as well as platforms for cell signalling. We have previously reported that plasma membrane-associated caveolae that lack cell surface access can be identified by electron microscopy. We now report the identification, after density gradient ultracentrifugation, of a subclass of very high-density apparently closed caveolae that were not labelled by cell surface protein labelling of intact cells. These caveolae contained caveolin-1 and caveolin-2. Another class of high-density caveolae contained caveolin-1, caveolin-2 and specifically fatty acid transport protein-1, fatty acid transport protein-4, fatty acyl-CoA synthetase, hormone-sensitive lipase, perilipin, and insulin-regulated glucose transporter-4. This class of caveolae was specialized in fatty acid uptake and conversion to triacylglycerol. A third class of low-density caveolae contained the insulin receptor, class B scavenger receptor-1, and insulin-regulated glucose transporter-4. Small amounts of these proteins were also detected in the high-density caveolae. In response to insulin, the insulin receptor autophosphorylation and the amount of insulin-regulated glucose transporter-4 increased in these caveolae. The molar ratio of cholesterol to phospholipid in the three caveolae classes varied considerably, from 0.4 in very high-density caveolae to 0.9 in low-density caveolae. There was no correlation between the caveolar contents of caveolin and cholesterol. The low-density caveolae, with the highest cholesterol concentration, were particularly enriched with the cholesterol-rich lipoprotein receptor class B scavenger receptor-1, which mediated cholesteryl ester uptake from high-density lipoprotein and generation of free cholesterol in these caveolae, suggesting a specific role in cholesterol uptake/metabolism. These findings demonstrate a segregation of functions in caveolae subclasses.

  • 28.
    Jakobsson, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pulmonary Medicine. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Respiratory Medicine UHL.
    Jorfeldt, Lennart
    Stockholm.
    Oxygen supplementation increases glucose tolerance during euglycaemic hyperinsulinaemic glucose clamp procedure in patients with severe COPD and chronic hypoxaemia2006In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, Vol. 26, no 5, 271-274 p.Article in journal (Refereed)
    Abstract [en]

    Investigations in chronic obstructive pulmonary disease (COPD) patients have shown impaired glucose tolerance in hypoxic COPD patients, compared with COPD patients with normal arterial blood gases. In healthy subjects, hypoxaemia or stay at altitude, have been shown to alter glucose metabolism. At altitude the effect seems to be dependent on duration of stay. A short stay is associated with insulin resistance, a longer stay gives rise to increased glucose uptake. The euglycaemic hyperinsulinaemic glucose clamp technique is a method to study glucose tolerance and enables determinations of glucose clearance in peripheral tissues. We investigated six COPD patients [forced expiratory volume in 1 s 0.7 ± 0.2 l (mean ± SD)] with chronic hypoxaemia (PaO2 7.9 ± 0.6 kPa at rest, breathing air), with and without oxygen supplementation, using the glucose clamp technique. Net peripheral glucose uptake was 5.5 ± 1.2 and 7.1 ± 1.6 mg (kg*min)-1 (+29%) breathing air and supplemental oxygen, respectively (P = 0.03). The tissue sensitivity to insulin increased 32% (P = 0.03) with oxygen supplementation. The results indicate that normalization of oxygen saturation in COPD patients with chronic hypoxaemia may have an immediate effect on glucose tolerance and tissue sensitivity to insulin in these patients. © 2006 Blackwell Publishing Ltd.

  • 29. Samuelsson, U
    et al.
    Hanås, Ragnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Whiss, Per A
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Ludvigsson, J
    Blood glucose peaks give high HbA1c2004In: International Society for Pediatric and Adolescent Diabetes ISPAD,2004, 2004Conference paper (Other academic)
  • 30.
    Lindberg, Lina
    Linköping University, Department of Physics, Chemistry and Biology.
    Evaluation of Different Enzymes and Yeasts, and Their Impact on Bioethanol Production Based on Debranned Wheat2009Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Bioethanol is a fuel of tomorrow, and progress in the use of enzymes and reduction of non-fermentable materials by debranning will probably be a part to make it more economical with low environmental impact.

     

    Ethanol production based on debranned wheat was optimized in this study by batch experiments as well as continuous experiments in laboratory scale. Enzymes from Novozymes and Genencor were compared and no significant differences were discovered between the different set of enzymes. The yeast strains Ethanol Red and AmyloFerm were compared with traditional baker’s yeast and baker’s yeast were surprisingly the fastest to ferment, but Ethanol Red had higher viability during fermentation. Protease addition during saccharification does not seem to improve fermentation with baker’s yeast. Prolonged liquefaction and saccharification time does probably not have any large impact on glucose yield. The continuous lab-scale process has a potential to be a realistic model but the stirring has to be improved and the pipe diameter increased.

  • 31.
    Jinnelöv, Anders
    Linköping University, Department of Physics, Chemistry and Biology, Biochemistry.
    Investigation of small molecules binding to UDP-galactose 4'-epimerase: A validated drug target for Trypanosoma brucei, the parasite responsible for African Sleeping Sickness.2009Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    African sleeping sickness is a parasitic infection spread by the protozoan parasite Trypanosoma brucei, and drugs used today are toxic and painful. Galactose metabolism is essential for the survival of T. brucei and without a functional UDP galactose 4’ epimerase (GalE) galactose starvation occurs and cell death will follow. In this Master thesis project two assays observing binding of small molecules to TbGalE has been investigated in attempt to establish an assay that in the future could be used for screening for drugs.

    TbGalE was biotinylated through the Pinpoint Xa vector and expressed in E. coli cells. The protein was successfully immobilized to a Streptavidin chip for Surface Plasmon Resonance experiments and the binding of the substrates UDP-galactose and UDP-glucose was observed. Unfortunately, the assay was not optimal for screening due to low signal response. However, the established protocol for expressing biotinylated proteins that bind to Streptavidin surfaces could be used in further experiments with TbGalE and other drug targets for African sleeping sickness.

    The fluorescent sugar nucleotide analogue UDPAmNS, which is a known inhibitor for E. coli GalE, was synthesised and purified and then used to establish a displacement assay. IC50 of UDPAmNS against TbGalE was determined and a synergic effect in fluorescence between the protein and the inhibitor was proven. Further, evidence for a reduction in fluorescence by displacing UDPAmNS with UDP was obtained. This reduction in fluorescence was also shown by a predicted cofactor inhibitor. The IC50 against TbGalE for this compound was determined before the displacement assay, which showed that the cofactor inhibitor, at least partly, binds to the active site of TbGalE. The UDPAmNS displacement assay could have the potential of becoming a robust screening assay for TbGalE, in the effort to find a better drug for African sleeping sickness.

  • 32.
    Nyman, Elin
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology .
    Hierarchical modeling of diabetes: a pilot study2009Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In type 2 diabetes the concentration of glucose in the blood is increased, and tissues like fat and musclebecome less sensitive to insulin. These two phenomena are interrelated, but since the glucose-insulininterplay is highly complex, many aspects are still not understood. Here, a model-based approachmight help. Nevertheless, also a model-based approach has a limited impact, unless models for thesub-systems can be combined into a model for the whole-body regulation. Such a multi-level,module-based model is referred to as a hierarchical model, and this thesis is a proof-of-principle studyfor the future development of such models.

    We have extended one of the best available models for the whole-body regulations, to include azoomable module for the fat tissue. The first step was to implement the whole-body model in thesoftware MathModelica, which support hierarchical modeling. Second, the originally mergedinsulin-responding module was sub-divided, so that a fat tissue was singled out. Third, a model for theinput-output profile for the fat tissue was developed by combining mechanistic knowledge withexisting and novel data from human fat cells. Finally, this detailed model was fitted to the profile of theoriginal fat model, and inserted in the whole-body model, with negligible effect on the whole-bodysimulations.

    The resulting model has the ability to translate mechanistically oriented simulations on the biochemicallevel, which is the level were drugs act, to the whole-body level, which is of clinical interest. This is aquantum leap forward for modeling, and understanding, glucose homeostasis and type 2 diabetes.

  • 33.
    Nilsson, S F E
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Mäepea, O
    Alm, A
    Narfström, K
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine.
    Ocular blood flow and retinal metabolism in abyssinian cats with hereditary retinal degeneration2001In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, Vol. 42, no 5, 1038-1044 p.Article in journal (Refereed)
    Abstract [en]

    Purpose. To investigate if retinal blood flow decreases with progression of the disease in Abyssinian cats with progressive retinal atrophy (PRA), to examine if the choroidal blood flow was affected by the disease, and to determine the uptake of glucose and formation of lactate in the outer retina. Methods. Local blood flow in different parts of the eye was determined with radioactive microspheres, in 9 normal cats and in 10 cats at different stages of PRA. Three blood flow determinations were made in each animal, during control conditions, after IV administration of indomethacin and after subsequent administration of Nw-nitro-L-arginine (L-NA). Blood samples from a choroidal vein and a femoral artery were collected to determine the retinal formation of lactate and uptake of glucose. Results. In Abyssinian cats with PRA (n = 10), the retinal blood flow was significantly (P = 0.01) lower than in normal cats (n = 9) during control conditions, 6.4 ▒ 1.7 compared with 14.1 ▒ 1.9 g min-1 (100 g)-1. The vascular resistance in the iris and ciliary body was significantly higher in the cats at a late stage of PRA, both compared with normal cats and to cats at an early stage of the disease, whereas the choroidal vascular resistance was not significantly affected. Indomethacin had no effect on ocular blood flows in normal cats, but in cats with PRA, iridal blood flow was more than doubled after indomethacin. The retinal formation of lactate was significantly (P = 0.001) lower in cats with PRA than in normal cats, 0.111 ▒ 0.035 (n = 8) compared with 0.318 ▒ 0.024 (n = 8) ╡mol rain-1. The uptake of glucose was not significantly different in cats with PRA. Conclusions. Retinal blood flow is severely decreased in Abyssinian cats at a late stage of retinal degeneration, whereas the choroidal microcirculation is not significantly affected by the disease. At a late stage of retinal degeneration, vascular resistance in the iris is significantly increased, which at least in part could be caused by cyxlooxygenase products.

  • 34.
    Permert, Johan
    Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
    Glucose metabolism in patients with exocrine pancreatic adenocarcinoma1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Carc.inoma of the exocrine pancreas is the fifth leading cause of cancer death in the Western world and the survival rate is one of the lowest for cancers of any site. Pancreatic cancer is characterized by pronounced, early cachexia and frequent metabolic complications. An increased incidence of diabetes or impaired glucose tolerance have been reported in pancreatic cancer patients. Two different hypotheses for this association have been presented, one suggesting that diabetes is a predisposing factor for pancreatic cancer and the other suggesting that the diabetic state is a consequence of the malignant disease.

    In the present study, 50 patients with exocrine pancreatic adenocarcinoma were studied, 11 of whom were found suitable for radical surgery. These eleven patients were studied both preoperatively and 3 months after subtotal pancreatectomy. Healthy subjects, patients with cancer of other sites and diabetic patients without any malignancy were investigated as controls. The incidence of diabetes and impaired glucose tolerance was investigated. Insulin secretion from pancreatic cancer patients was evaluated in the basal state, during hyperglycemia and after glucagon stimulation. Whole-body and peripheral insulin sensitivity were determined. The abundance and distribution pattern of endocrine cells, and the concentration of pancreatic islet hormones were investigated in control tissues ·and human exocrine pancreatic adenocarcinomas. The metabolic effect of extracts of these tumors on muscle glycogen synthesis was studied in vitro. Concentrations of islet hormones were determined in plasma in the basal state, during hyperglycemia and after stimulation by glucagon. Production of islet amyloid polypeptide (IAPP) was evaluated by studies of mRNA expression and peptide immunoreactivity in pancreatic adenocarcinomas, in tissue adjacent to the tumor and in normal pancreas.

    Diabetes or impaired glucose tolerance was found in 74% of the patients with pancreatic cancer, and this high frequency resulted mainly from newly-diagnosed diabetes. The diabetic state was more a consequence of profound insulin resistance rather than an impaired insulin secretion. After subtotal pancreatectomy, the diabetic state, glucose tolerance and insulin sensitivity were improved despite a marked decrease in insulinsecretion. Endocrine cells were found in 80% of the adenocarcinomas, predominantly in well-differentiated adenocarcinomas. Extracts from the tumors contained islet hormones, but in varying concentrations and without any correlation to diabetic state. Tumor extracts from diabetic but not from non-diabetic pancreatic cancer patients inhibited glycogen synthesis in skeletal muscle. This metabolic effect could not be explained by the concentrations of the diabetogenic peptides in the extracts. Plasma IAPP, glucagon and somatostatin were normalized after subtotal pancreatectomy. The pattern of hormonal changes seen was suggestive of a paracrine action of pancreatic adenocarcinomas on the adjacent pancreatic islets. This was supported by the normal IAPP mRNA-staining in the absence of IAPP-immunoreactivity in endocrine pancreatic tissues adjacent to the tumor. In conclusion, diabetes occurs with an increased frequency in patients with exocrine pancreatic adenocarcinoma. The diabetic state is closely related to the tumor itself and is a consequence rather then the cause of the malignant disease. Overall the results indicate that the diabetic state results from the tumor acting either directly or indirectly.

  • 35.
    Svensson, Markus
    Linköping University, Department of Biomedical Engineering.
    Evaluation of the reconstruction algorithm, Ordered Subsets Expectation Maximization, in whole body Positron Emission Tomography2008Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    A Positive Electron Tomography/Computed Tomography devise was installed in theX-ray section at US Linköping in May 2007. Positive Electron Tomography examinations with 18F-fluoro-deoxy-glucose are mainly used for tumor examinations. During 2007 occurred approximately 200 examinations and in 2008 600 are planned. Today there are two reconstruction methods commercially available, Filtered Back projection and Maximum Likelihood Expectation Maximiza tion, used in the faster version called Ordered Subsets Expectation Maximization. The image quality in Positive Electron Tomography depends on the choice of reconstruction method and the settings of its parameters. We have performed a physical phantom study with Positive Electron Tomography to determine optimal parameters for the iterative reconstruction algorithm Ordered Subsets Expectation Maximization. To find out whether or not the quality of the image can be improved, so that the patient received radiation dose and/or examination time can be lowered. The phantom used was a NEMA IEC Body PhantomTM, designed to mimic smallhot lesions typical in 18F, Fluorine-18 PET, and all calculations were done according to the NEMA NU2-2001 protocol.

    The main conclusion from this project is that a higher level of contrast can be reached, compared to the one clinically obtained today. Using more iterations then recommended from the manufacturer.

  • 36.
    Jamali, R.
    et al.
    Linköping University, Department of Biomedicine and Surgery.
    Mohseni, S.
    Simultaneous glucose measurement in blood, peripheral nerve, muscle and skin in control and diabetic ratsManuscript (Other academic)
  • 37.
    Mörelius, E.
    et al.
    Linköping University, Department of Molecular and Clinical Medicine.
    Theodorsson, E.
    Stress at three-month immunization: A randomized, placebo-controlled trial of parents’ and infants’ salivary cortisol response in relation to the use of pacifi er and oral glucoseManuscript (Other academic)
  • 38.
    Larsson, Johan
    Linköping University, The Department of Physics, Chemistry and Biology.
    High-throughput Fed-batch Production of Affibody® molecules in a novel Multi-fermentor system2005Independent thesis Basic level (professional degree), 20 points / 30 hpStudent thesis
    Abstract [en]

    The present Master thesis describes the development and optimization of a fed-batch process for production of recombinant proteins in Escherichia coli BL21(DE3) in a multi-fermentor system. The system consists of six 1-liter fermentors, capable of producing 500-1500 μg/mL with present protocol.

    Response surface methodology (RSM) was used for multivariable optimization regarding cultivation time, pH, temperature and feed rate. Optimal protein expression conditions were found out to be 17.8 h cultivation time, 36.7 ºC, pH 6.8 and a feed rate corresponding to specific growth of 0.23 h-1, on glucose substrate. The aggregation of expressed proteins to inclusion bodies, could not be affected by the various growth conditions employed during cultivations.

    A study was conducted regarding growth conditions effect on phosphogluconoylation of expressed proteins. In ten fed-batch cultivations on glucose, LC/MS analysis showed a gluconoylated fraction with additional 178 Da mass, but no correlation between growth conditions and gluconoylation could be found. In two fed-batch cultivations on glycerol-feed, a lower feed rate resulted in no gluconoylation, while a higher did. An explanation would be that the lower amount of available intra-cellular carbon limits formation of gluconoylation precursors.

  • 39.
    Aldén, Anna
    Linköping University, The Department of Physics, Chemistry and Biology.
    Optimization of the Liquefaction Process in Bioethanol Production & Development of Method for Quantification of Nonsolubilized Starch in Mash2008Independent thesis Basic level (professional degree), 20 points / 30 hpStudent thesis
    Abstract [en]

    Ethanol production at Lantmännen Agroetanol AB in Norrköping began in December 2000. The objective of this master's thesis is to find and optimize factors affecting the yield of the liquefaction, a part of the upstream process. To measure successfulness of liquefaction it is desired that amount of non-solubilized starch is quantified, and hence a method for determination of non-solubilized starch in mash has to be developed.

    Starch is a carbon reserve in plants. Starch granules are polymers of amylose and amylopectin which are polysaccharides of glucose. When a starch/water solution is heated the starch granules start to absorb water and swell, a process termed gelatinization. The swelling makes the granules susceptible to hydrolysis by enzymes such as alpha-amylase, this is called liquefaction. Eventually the granular structure is broken and the slurry contains solubilized starch which can be saccharified to glucose by glucoamylase. In the bioethanol production process, the milled grain is mixed with water and enzymes. The slurry is heated, gelatinization and liquefaction occurs. Saccharification occurs simultaneously to fermentation. Ethanol is purified from the fermented mash during downstream processing.

    Starch in the form of starch granules cannot be quantified. The adopted principle for determination of non-solubilized starch in liquefied mash is to wash away the solubilized starch, then quantitatively hydrolyze non-solubilized starch to glucose and quantify glucose.

    To find and optimize factors significant for yield of liquefaction multiple factor experiments were conducted where eight factors were studied. pH, temperature in mixtank and temperature in liquefaction tank 1 were the most significant factors. The temperature in liquefaction tank 1 should be kept as is is at 74°C. A small rise in pH should shorten the mean length of dextrins which is preferable. An increase of pH from 5.2 to 5.4 is therefore proposed. The temperature in mixtank should also be increased by a few degrees. The yield of the process should be carefully evaluated during the modifications.

  • 40.
    Johansson, Alexandra
    Linköping University, Department of Physics, Chemistry and Biology.
    Physiological stress and behavioural differences in broiler breeder hens subjected to daily and 5:2 feed restriction regimens2016Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    Feed restriction in the parental stock of meat producing chickens, broiler breeders, is essential in order to decrease the high growth rate that they are genetically selected for. The feed restriction does however lead to chronic hunger and stress. Stress can be measured by counting H/L ratios and the method of manually counting H/L ratios was evaluated. The method was not a good way to ensure reliable individual H/L ratios but still gives an H/L ratio indication on a group level and was therefore still used in the study. Two different feeding regimens were investigated in the study: 5:2 skip-a-day (SKIP) with two fasting days and daily feed restriction (CTRL), with chickens sampled at 9 and 12 weeks of age. There was no significant difference in body mass between the treatments at either age. SKIP chickens had significantly higher H/L ratios compared to CTRL at 12 weeks of age (P=0.020), but both treatments had H/L ratios above the reported limit of stress (0.5). The SKIP group on a feeding day significantly increased plasma glucose levels during the day (10.3 to 11.5 mmol/L, P=0.020) and had significantly higher liver mass and liver glycogen levels compared to the CTRL (P≤0.001). The SKIP group were also less fearful on fasting days and significantly less active than the CTRL (P≤0.050), regardless of age or daily feed differences. The conclusion was that both treatments were stressed but skip-a-day chickens were habituated to their regimen and did not experience worse welfare than daily fed broiler breeders.

  • 41.
    Bzdula, Jessica
    Linköping University, Faculty of Health Sciences.
    Den preanalytiska fasen – Hur viktigt är det att blanda serumrören?2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Approximately 2/3 of all pre-analytical errors occur in the pre-analytical phase, where mixing of sample tubes directly after sampling is one of the factors. The purpose of the study was to compare the analytical results for the glucose, lactate dehydrogenase and potassium in serum from mixed tubes with unmixed tubes. The study's aim was also to investigate the durability of these three analytes at room temperature (25 °C) for seven days.

    Method: 100 mixed and 100 unmixed serum tubes with gel, from 100 patients, were analyzed on Architect ci2800. Assay results were statistically compared with the paired t-test. All the serum tubes were stored at room temperature for seven days and the three analytes were analyzed daily. The results of the analysis were compared statistically by ANOVA.

    Results: No statistical significant difference (p > 0,05) was found for glucose and potassium between the unmixed and mixed tubes. Lactate dehydrogenase showed a small but statistical significant difference (p < 0,05) between the unmixed and mixed tubes. The differences in durability between day 1, day 2 and day 7 of the glucose, lactate dehydrogenase and potassium was found to be statistic significant (p < 0,05).

    Conclusion: This study indicates that it is not necessary to mix the serum tubes immediately after the blood sampling, however it is important to mix other types of tubes, such as citrate tube. Therefore it is good to create a routine while you are mixing all the tubes. Glucose is the most stable analyte in room temperature for seven days while the potassium is the least stable.

  • 42.
    Rickardsson, Isabelle
    Linköping University, Department of Biomedical Engineering.
    Patient-Generated Health Data: Professionals' Opinions and Standardized Data Transfer2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The ongoinging demographic change will increase the demands on health care with an increase of old people suffering from long-term conditions in need of care. One way of meeting this increasing demand is to combine the use of modern technology and the involvement of patients by letting patients monitor their health themselves.  The use of patient-generated health data (PGHD) can benefit both patients and the health care and is an area that is being studied internationally. In this thesis work, two parts of the area of using PGHD in health care have been studied. First eleven professionals from the field of health care (both medical professionals, strategists and project leaders) were interviewed regarding their opinions on PGHD. They were generally positive to the phenomena and mentioned several types of measurements they found to be suited for PGHD. Among these measurement types were blood pressure, weight, blood glucose, electrocardiogram (ECG), peak expiratory flow (PEF), blood oxygen saturation and a variety of blood tests.

    The professionals found the greatest benets of PGHD to be the increased freedom and quality of life it offers to patients and the increased engagement to their own care it may lead to. The greatest concerns were related to technology problems and the patients using the measurement devices incorrectly.

    The second part of the work investigated how measurements of weight, blood pressure and ECG would be transferred from the device used by the patient to the electronic health record (EHR) in a standardized way. For the transfer being standardized, the study followed the Continua design guidelines (CDG), which are based on international standards and aim to achieve plug-and-play interoperability among health care devices and systems.

    This part of the study was carried out by studying the CDG documents as well as the standards to which they refer. The measurement data from the three device types were all described to be handled as numeric values, but in different formats. The weight is a single value, the blood pressure is a compound of values: systolic, diastolic and mean arterial pressure, and the ECG is an array of values. All measurement data is contained in a specic message together with additional data such as device type, device manufacturer, a reference ID and the date and time of the measurement. The data message is transferred from the measurement device to an application hosting device (AHD) with either a touch area network interface (using Near-Field Communications), personal area network interface (using USB or Bluetooth communication) or local area network interface (using ZigBee communication). From the AHD the data transfer chain continues until the data reaches the EHR.

  • 43.
    Hedborg, Julia
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    A Printed Biosensor Based on an Organic Electrochemical Transistor with Mediated Gate Electrode2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Biosensor technology is an expanding field of research and there is a great market demand for low-cost disposable sensors. The aim of this project was to come up with a printed, disposable biosensor for glucose based on an organic electrochemical transistor (OECT). The organic semiconductor PEDOT:PSS was used as the material for the transistor channel and the gate electrode was made of carbon bulk modified with the different redox mediators potassium ferricyanide and ferrocene and the catalyst cobalt phthalo cyanine (CoPC) respectively. The enzyme glucose oxidase, that oxidases glucose, was used as sensing element and was immobilised on top of the gate electrodes. The sensor was fabricated with screen-printing, a low-cost technique that offers high throughput and is robust, simple and flexible. The gate electrodes were evaluated with cyclic voltammetry and chronoamperometry before integrated in the transistor device. The results showed that electrodes containing CoPC could detect hydrogen peroxide, a product in the reaction between glucose and the enzyme. Ferricyanide-electrodes showed good results regarding the activity of the mediator but no good results were achieved for the ferrocene-mediated electrodes. Transistor devices with CoPCmediated electrodes gave a response for 1mM hydrogen peroxide at 0.55V with good reproducibility, but the sensitivity needs to be further investigated. Transistor measurements with ferricyanide-mediated gates at 0.25V and glucose oxidase indicated that the glucose sensing works with these electrodes as well, but more measurements are needed. It was also concluded that the geometry of the transistor device had an influence on the relative response for the sensor, and a long channel proved to be better than a wide. The method used to fabricate the sensor offers great variation options and few production steps and the mediator approach enables inexpensive material costs.

  • 44.
    Broman, Eva
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Printable Biosensors based on Organic Electrochemical Transistors with a Platinized Gate Electrode2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    There is a great demand for low-cost disposable sensors in a variety of markets, such as the food chainand health care. No assay is performed more than that of glucose and approximately 85 % of the entirebiosensor market accounts for glucose biosensors. Each year, 6 billion glucose assays are performed andthe majority of them are based on electrochemical detection. Organic electrochemical transistors(OECTs) have favorable properties in terms of low operating voltages and have previously been used asbase for electrochemical detection of glucose. A low-cost disposable biosensor can be achieved by theuse of high throughput printing techniques. Up until now, no printable biosensors based on organic electrochemicaltransistors have been developed.

    In this thesis a printable miniaturized prototype for a glucose biosensor based on an OECT with a platinizedgate electrode has been designed, developed and evaluated. The biosensor has been functionalizedwith the enzyme glucose oxidase. Different platinum deposition techniques have been used to depositplatinum onto the printed carbon gate electrode: electrodeposition, platinum nanoparticle solutiondeposited either by inkjet printing or pipetting and thermal evaporation.

    The gate electrodes were characterized with cyclic voltammetry in hydrogen peroxide, ferricyanide andglucose. The characterizations revealed no significant differences between the different deposition techniques.However, with gate electrodes produced by printed carbon followed by electrodeposition ofplatinum it was possible to sense glucose in a concentration in the range of the values for diabetic persons.Thus, the electrodes are a promising option as gate electrodes in a glucose biosensor based on anOECT. The characteristics of the OECT revealed that the responses resembled a transistor.

  • 45.
    Bergenholm, Linnéa
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences.
    Modeling as a Tool to Support Self-Management of Type 1 Diabetes2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Type 1 diabetes (T1D) is an auto-immune disease characterized by insulin-deficiency. Insulin is a metabolic hormone that is involved in lowering blood glucose (BG) levels in order to control BG level to a tight range. In T1D this glycemic control is lost, causing chronic hyperglycemia (excess glucose in blood stream). Chronic hyperglycemia damages vital tissues. Therefore, glycemic control must be restored.

    A common therapy for restoring glycemic control is intensive insulin therapy, where the missing insulin is replaced with regular insulin injections. When dosing this compensatory insulin many factors that affect glucose metabolism must be considered. Linkura is a company that has developed tools for monitoring the most important factors, which are meals and exercise. In the Linkura meal and exercise tools, the nutrition content in meals and the calorie consumption during exercise are estimated. Another tool designed to aid control of BG is the bolus calculator. Bolus calculators use input of BG level, carbohydrate intake, and insulin history to estimate insulin need. The accuracy of these insulin bolus calculations suffer from two problems. First, errors occur when users inaccurately estimate the carbohydrate content in meals. Second, exercise is not included in bolus calculations. To reduce these problems, it was suggested that the Linkura web tools could be utilized in combination with a bolus calculator.

    For this purpose, a bolus calculator was developed. The bolus calculator was based on existing models that utilize clinical parameters to relate changes in BG levels to meals, insulin, and exercise stimulations. The bolus calculator was evaluated using data collected from Linkura's web tools. The collected data showed some inconsistencies which cannot be explained by any model.  The performance of the bolus calculator in predicting BG levels using general equations to derive the clinical parameters was inadequate. Performance was increased by adopting an update-algorithm where the clinical parameters were updated daily using previous data. Still, better model performance is prefered for use in a bolus calculator.  

    The results show potential in developing bolus calculator tools combined with the Linkura tools. For such bolus calculator, further evaluation on modeling long-term exercise and additional safety features minimizing risk of hypoglycemia are required.

  • 46.
    Andreas, Svensson
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Model Predictive Control with Invariant Sets in Artificial Pancreas for Type 1 Diabetes Mellitus2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This thesis deals with Model Predictive Control (MPC) for artificial pancreas for Type 1 Diabetes Mellitus patients. A control strategy exploiting invariant sets in MPC for blood glucose level control is developed, to the authors knowledge for the first time. The work includes various types of invariant sets relevant for the artificial pancreas problem, and different ways to incorporate them into the MPC strategy. The work is an extension to the zone MPC controller for artificial pancreas developed at University of California Santa Barbara and Sansum Diabetes Research Institute.

    The evaluation of the proposed control strategy is done in silico in the U.S. Food and Drug Administration approved metabolic simulator. The trials show some promising results in terms of more rapid meal responses and decreased variability between the subjects than the zone MPC. An attempt to robust control employing invariant sets proved to be less promising in the evaluations. The results indicate that the direct application of known robust control techniques is not appropriate, and that more appropriate robust control techniques must be searched for, or developed, more specific to the artificial pancreas control.

    Altogether, this thesis pinpoints a possible future direction of artificial pancreas control design, with MPC based on invariant sets.

  • 47.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Prevention of adverse events in juvenile diabetes2004In: Minerva Pediatrica, ISSN 0026-4946, Vol. 56, no 3, 277-290 p.Article in journal (Refereed)
    Abstract [en]

    The most severe adverse event of juvenile diabetes is death. Still these days it happens that children with diabetes die from diabetes before having received any treatment at all, sometimes probably undiagnosed. We have to improve the awareness and knowledge, both in the general population and also among health care staff and physicians. Retarded growth and development was seen earlier, but is now rare. But long-term complications affecting primarily blood vessels and nerves are still a real threat and may develop already after a few years. Unless diabetes is well treated, the disease is as dangerous as ever before. We know that a good metabolic control prevents complications, but not how to reach such control in many patients. Severe hypoglycemia has been feared to limit our possibilities to reach good metabolic balance. However, near-normal HbA1c must not be accompanied by increasing incidence of severe hypoglycemia. Too many patients are never offered an insulin treatment as physiological as possible. Adequate use of basal and bolus insulin is a prerequisite. Continuous adjustments should be monitored on the basis of glucose profiles, but without effective education and psychosocial support the treatment tends to fail. Intense treatment of diabetes may become a heavy burden, an "adverse event" in itself, for the patient and the parents of a diabetic child. Psychosocial support is often needed. Realistic information already from the onset of the disease is important, together with optimism, encouragement and not only criticism. Short-term goals and realistic agreements may help the patient to accept the disease. Independence and capacity to manage the treatment successfully contribute to a good metabolic control and also improves quality of life. Children with diabetes cannot expect a "normal" life, but they should be able to expect a long, active, exciting and happy life.

  • 48.
    Karlsson, Margareta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Thorn, Hans
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Danielsson, Anna
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Stenkula, Karin
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Öst, Anita
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Gustavsson, Johanna
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Colocalization of insulin receptor and insulin receptor substrate-1 to caveolae in primary human adipocytes2004In: European Journal of Biochemistry, ISSN 0014-2956, E-ISSN 1432-1033, Vol. 271, no 12, 2471-2479 p.Article in journal (Refereed)
    Abstract [en]

    Caveolae are plasma membrane invaginations with several functions, one of which appears to be to organize receptor mediated signalling. Here we report that in primary human subcutaneous adipocytes the insulin receptor was localized to caveolae by electron microscopy/immunogold detection and by isolating caveolae from plasma membranes. Part of insulin receptor substrate 1 (IRS1), the immediate downstream signal mediator, was colocalized with the insulin receptor in the plasma membrane and caveolae, as demonstrated by immunofluorescence microscopy, immunogold electron microscopy, and immunogold electron microscopy of transfected recombinant HA-IRS1. In contrast, rat epididymal adipocytes lacked IRS1 at the plasma membrane. Depletion of cholesterol from the cells using β-cyclodextrin blocked insulin stimulation of glucose uptake, insulin inhibition of perilipin phosphorylation in response to isoproterenol, and insulin stimulation of protein kinase B and Map-kinases extracellular signal-related kinase (ERK)1/2 phosphorylation. Insulin-stimulated phosphorylation of the insulin receptor and IRS1 was not affected, indicating that caveolae integrity is required downstream of IRS1. In conclusion we show that insulin receptor and IRS1 are both caveolar proteins and that caveolae are required for both metabolic and mitogenic control in human adipocytes. Our results establish caveolae as foci of insulin action and stress the importance of examining human cells in addition to animal cells and cell lines.

  • 49.
    Eriksson, Mats
    et al.
    Department of Paediatrics, Örebro University Hospital.
    Finnström, Orvar
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Can daily repeated doses of orally administered glucose induce tolerance when given for neonatal pain relief?2004In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 93, no 2, 246-249 p.Article in journal (Refereed)
    Abstract [en]

    Aim: Orally administered sweet solutions have a pain-relieving effect during painful procedures in newborn infants. The underlying mechanism is not fully understood, but, from the results of animal research, an opioid-like mechanism is often suggested. The aim of this study was to determine whether repeated doses of orally administered glucose would cause tolerance to glucose.

    Methods: Fifty-seven healthy, full-term infants were recruited on the day of birth to receive three daily doses of either 1 ml 30% glucose or sterile water for 3–5 d, after which routine blood samples were collected by heel-lance. All infants received 1 ml 30% glucose before the heel-lance was carried out. Crying time, Premature Infant Pain Profile scores and changes in heart rate were used as pain measures.

    Results: No differences were found between the groups, either in demographic data or in the outcome variables.

    Conclusion: No tolerance was observed under the conditions prevailing in this study. However, we cannot rule out an endogenous opioid mechanism. What is clinically important is that repeated doses of glucose do not decrease the pain-relieving effect.

  • 50.
    Påhlsson, Peter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Spitalnik, Steven
    Spitalnik, Patrice
    Fantini, Jacques
    Rakotonirainy, Olivier
    Ghardashkhani, Sohbat
    Lindberg, Jan
    Konradsson, Peter
    Larson, Göran
    Characterization of galactosyl glycerolipids in the HT29 human colon carcinoma cell line2001In: Archives of Biochemistry and Biophysics, ISSN 0003-9861, Vol. 396, no 2, 187-198 p.Article in journal (Refereed)
    Abstract [en]

    Glycoglycerolipids constitute a family of glycolipids with apparently very restricted expression in human tissues. They have previously been detected only in the testis and the nervous system. In the present study, two glycoglycerolipids were isolated from the HT29 human colon carcinoma cell line. The glycoglycerolipids were structurally characterized as a monogalactosylglycerolipid (1-O-alkyl-2-O-acyl-3-O-(▀-galactosyl)-sn-glycerol) and a digalactosylglycerolipid (1-O-alkyl-2-O-acyl-3-O-(▀-galactosyl(1-4)a-galactosyl)-sn- glycerol) using NMR and mass spectrometry. This digalactosylglycerolipid has not previously been structurally characterized. When HT29 cells were allowed to differentiate into more enterocyte-like cells by culture in glucose-free medium, expression of both of these glycoglycerolipids was greatly diminished. The presence of glycoglycerolipids in a human colon carcinoma cell line indicates that expression of this family of glycolipids may not be as restricted as previously thought. Instead this class of glycolipids may serve as differentiation antigens in various normal tissues and in tumor development. The Gala1-4Gal epitope was previously identified as a receptor for bacterial adhesins and toxins. The finding that this epitope is also linked to a glycerolipid moiety opens up new possible roles for this carbohydrate receptor in intracellular signaling.

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