ABSTRACT
Lately, there has been high interest in electrolysis under dynamic conditions, the so-called pulsed electrolysis. Different studies have shown that in pulsed electrolysis, selectivity towards certain products can be improved compared to steady-state operation. Many groups also demonstrated that the selectivity can be tuned by selection of pulsing profile, potential limits, as well as frequency of the change. To explain the origin of this improvement, some modeling studies have been performed. However, it seems that a theoretical framework to study this effect is still missing. In the present contribution, we suggest a theoretical framework of nonlinear frequency response analysis for the evaluation of the process improvement under pulsed electrolysis conditions. Of special interest is the DC component, which determines how much the mean output value under dynamic conditions will be different from the value under steady-state conditions. Therefore, the DC component can be considered as a measure of process improvement under dynamic conditions compared to the steady-state operation. We show that the DC component is directly dependent on nonlinearities of the electrochemical process and demonstrate how this DC component can be calculated theoretically as well as how it can be obtained from measurements.
ABSTRACT
The transferrin (Tf) family of iron binding proteins includes important endogenous modulators of the immune function that may modulate autoimmune diseases. To define more clearly the role of apotransferrin (apoTf) in type 1 diabetes we determined the impact of this protein on type 1 diabetes as investigated in islet cells, animal models and patient sera. First, we demonstrated that recombinant apoTf counteracts the cytokine-induced death of murine pancreatic islet cells. Secondly, human apoTf administration favourably influences the course of type 1 diabetes in animal models, resulting in protection against disease development that was associated with reduction of insulitis and reduced levels of proinflammatory cytokines. Finally, we confirmed that patients with newly diagnosed type 1 diabetes manifest significantly lower apoTf serum levels compared to healthy controls and patients with long-lasting disease. In conclusion, our data suggest the apoTf pivotal role in the perpetuation of type 1 diabetes pathology.
Subject(s)
Apoproteins/immunology , Diabetes Mellitus, Type 1/immunology , Transferrin/immunology , Adult , Animals , Apoproteins/blood , Apoproteins/chemistry , Cell Line, Tumor/drug effects , Cytokines/metabolism , Cytokines/pharmacology , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 1/prevention & control , Disease Progression , Female , Humans , Insulinoma/pathology , Islets of Langerhans/drug effects , Islets of Langerhans/immunology , Islets of Langerhans/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Inbred NOD , Pancreatitis/immunology , Pancreatitis/prevention & control , Rats , Rats, Inbred BB , Recombinant Proteins/pharmacology , T-Lymphocyte Subsets/immunology , Transferrin/chemistry , Young AdultABSTRACT
The aim of this study was to estimate the possibility of predicting the course of type 1 diabetes. We analyzed the importance of islet cell antibody levels and residual beta cell function in 46 newly diagnosed patients with diabetes. Islet cell antibodies (ICAs; Juvenile Diabetes Foundation [JDF] units) were determined at the time of diagnosis by the indirect immunofluorescent method. beta cell function was estimated by C peptide levels (nmol/L) before and after glucagon stimulation at the time of clinical remission. Of the 46 patients, 13 were ICA negative (group A). Among ICA-positive patients, ICAs were < 20 JDF units (group B) in 15, between 20 and 80 JDF in 9 (group C), and > 80 JDF in 9 (group D). In group A, 9 patients had clinical remission for 7.5 +/- 1.7 months. Their basal C peptide level was 0.26 +/- 0.05 nmol/L and it increased after stimulation to 44.5 +/- 2.5%. Ten patients in group B had remission for 6.2 +/- 1.5 months. Their basal C peptide levels (0.28 +/- 0.07 nmol/L) were similarly increased after stimulation (47.5 +/- 2.5%). In group C, all patients had remission and it was of the longest duration (14.7 +/- 1.5 months). They had the highest basal C peptide levels (0.45 +/- 0.12 nmol/L) with increases to 57.5 +/- 3.5%. Seven patients in group D with ICA levels > 80 JDF had a short remission (3.2 +/- 1.2 months) despite good basal C peptide levels (0.42 +/- 0.05 nmol/L) and excellent increases after stimulation (92.5%). Our results suggest that moderate levels of ICA are associated with good residual beta cell function and longer remission. Very high ICA levels (> 80 JDF) at the time of diagnosis despite better beta cell function are associated with short clinical remission. Therefore, high ICA levels could be a marker of strong autoimmune reaction and accelerated depletion of beta cell function.
