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- Hagberg, Jessika
(författare)
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Capillary zone electrophoresis for the analysis of low molecular weight organic acids in environmental systems
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Capillary zone electrophoretic (CZE) methods were developed to identify and quantify low molecular weight (LMW) organic acids in environmental samples. Sensitivity and selectivity were optimised by adapting the background electrolyte to the characteristics of analytes, and by using different modes of detection and injection. Electrokinetic injection mode in combination with an isotachophoretic state increased the sensitivity remarkably for LMW organic acids using UV detection. Calcium ions were added to the background electrolyte, inducing an on-column complexation between acids and calcium ions, which gave good separation of the acids. Mass spectrometric detection (compared to UV detection) increased the sensitivity when using hydrodynamic injection mode during analysis, and selectivity was improved by mass identification. A CZE method for determination of the dissociation constants of LMW organic acids in the pKa range of 3.54.5 was also developed. The developed procedures were applied to different areas where LMW organic acids play an important environmental role: Low molecular weight organic acids were analysed in rainwater and soil water in the low μg/l range, within ten minutes after sampling. Rapid analysis and high sensitivity are essential when studying samples with rapid turnover due to microbial activity and photodegradation. The use of CZE-ESI-MS proved to be a robust analytical tool for determining LMW organic acids in samples rich in interfering ions. Organic acids excreted by soil fungi as response to metal exposure was easily and rapidly quantified with CZE-ESI-MS compared to HPLC and CZE-UV analysis. Dissociation constants for isosaccharinic acid (ISA) and gluconic acid were determined by CZE to 3.87 and 3.64, respectively. The ability to make the determinations in the presence of impurities as well as not having to know the exact concentration of analyte were identified as the major benefits of CZE. Isosaccharinic acid was identified as the main degradation product from alkaline degradation of cellulose by CZE analysis. Long-term predictions on both cellulose degradation and ISA production were made based on three years of sampling data. A control sampling after seven years indicated that the degradation of cellulose and the production of ISA were lower than predicted.
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| 3. |
- Schölin, Anna
(författare)
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Diabetes in Young Adults : Remission, β-cell function and markers of inflammation
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 diabetes is caused by immuno-mediated β-cell destruction leading to insulin deficiency and hyperglycaemia. The decline in β-cell function and the clinical course after diagnosis vary. Whether the process of destruction of the β-cells is associated with markers of a non-specific inflammatory response is unknown. The aims of these studies were to identify factors of importance for clinical remission (low insulin need and normoglycaemia) and long-term β-cell function and estimate the degree of non-inflammatory response in type 1 diabetes in young adults. Clinical remission and β-cell function eight years after diagnosis were assessed and related to clinical, biochemical and immunological variables at diagnosis, including islet autoantibodies [ICA, GADA, IA-2A]. Markers of low-grade inflammation in plasma [CRP and IL-6] were estimated and the concentrations were related β-cell function [plasma C-peptide], glycaemic control and autoimmunity at diagnosis and the first year thereafter. The results showed that clinical remission occurred in about half of the patients with newly diagnosed type 1 diabetes. Preserved β-cell function eight years after diagnosis was observed in 16% of the patients classified at diagnosis as having autoimmune type 1 diabetes. Duration of remission was dependent on BMI, degree of metabolic derangement and presence of GADA at diagnosis. BMI at diagnosis was also of importance for preserved β-cell function after eight years of the disease, as were the amount of islet antibodies and presence of ICA. Elevated CRP levels were noted in the majority of cases at diagnosis and both CRP and IL-6 concentrations were stable the first year after clinical diagnosis. High concentrations of CRP and IL-6 did not relate to β-cell destruction or the degree of autoimmunity. CRP concentrations were higher in islet antibody negative than in positive patients. CRP also correlated positively to BMI, C-peptide at 12 months and to increasing HbA1c between six and 12 months. In general, females had shorter remissions, lower concentrations of serum bicarbonate and higher levels and prevalence of GADA at diagnosis, compared to males. Females also had higher HbA1c and CRP values the first year after diagnosis. In summary, BMI at diagnosis is a strong predictor of duration of remission and preservation of β-cell function. Elevated CRP concentrations are correlated to factors linked rather to insulin resistance than to β-cell destruction. Females appear to have a more acute onset and a more severe course of the disease than males.
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