Development and application of electroanalytical techniques for biological matrices

This thesis presents a study on the development and application of electrochemical techniques for analysis in biological fluids. Two main problems which occur when measurements are made directly in biological matrices were addressed. Firstly, interferences from other electro active components and secondly, adsorption of high molecular weight organic species (such as proteins) onto the electrode surface. Much of the work described utilised glassy carbon electrodes covalently modified by a diazonium salt coupling procedure. This method of modification produced stable electrode surfaces suitable for use in flowing streams and with organic solvents (such as those used in reversed phase-HPLC). The properties of the chemically modified electrodes (CMEs) could be varied by changing the para substituent of the aryl species grafted onto the electrode surface. Modification with p-phenylacetate and p-benzoate moieties generated CMEs which were negatively charged at physiological pH (7.4) and were selective for cationic analytes relative to anionic species. The suitability of these CMEs as probes for the measurement of the catecholamine neurotransmitter dopamine (DA) was investigated in detail. The CMEs exhibited fast response times to DA and good selectivity to DA over ascorbic acid making them suitable for DA measurements with fast timescale electrochemical techniques. Uncharged CMEs were also prepared using the diazonium salt procedure. The selectivity of p-alkylbenzene modified electrodes was investigated in batch and flow injection analysis conditions. The selective measurement of biologically important species (acetaminophen and chlorpromazine) over interferents (ascorbic acid and uric acid), was investigated. Chlorpromazine was able to be measured in the presence of uric acid using a retention-time based technique coupled with a p-phenylacetate/p-methylbenzene modified detector. The simultaneous determination of acetaminophen, ascorbic acid and uric acid was achieved at an array of modified detectors. Covalently modified electrodes were used in protein adsorption studies. The extent of protein adsorption was evaluated by monitoring the electrochemical response of suitable probe analytes. Protein adsorption was influenced by monolayer modification. Anionic groups close to the electrode surface did not affect protein adsorption whilst hydrophobic groups increased protein adsorption. Charged groups which extended further into solution decreased protein adsorption. Protein adsorption was also examined at different carbon materials, electrochemically pretreated glassy carbon and CMEs prepared by methods other than diazonium salt modification. Glassy carbon was less prone to adsorption of high molecular weight foul ants compared to other unmodified carbon electrodes. Some assembly of anionic surfactant on basal plane graphite and incorporation of anionic surfactant in graphite epoxy decreased protein adsorption relative to unmodified electrodes. Electrodes coated with the polymer, cellulose acetate, decreased protein adsorption but gave poor reproducibility and suffered from time-dependent response

PopMod: a longitudinal population model with two interacting disease states

This article provides a description of the population model PopMod, which is designed to simulate the health and mortality experience of an arbitrary population subjected to two interacting disease conditions as well as all other "background" causes of death and disability. Among population models with a longitudinal dimension, PopMod is unique in modelling two interacting disease conditions; among the life-table family of population models, PopMod is unique in not assuming statistical independence of the diseases of interest, as well as in modelling age and time independently. Like other multi-state models, however, PopMod takes account of "competing risk" among diseases and causes of death. PopMod represents a new level of complexity among both generic population models and the family of multi-state life tables. While one of its intended uses is to describe the time evolution of population health for standard demographic purposes (e.g. estimates of healthy life expectancy), another prominent aim is to provide a standard measure of effectiveness for intervention and cost-effectiveness analysis. PopMod, and a set of related standard approaches to disease modelling and cost-effectiveness analysis, will facilitate disease modelling and cost-effectiveness analysis in diverse settings and help make results more comparable

Intravenous tPA therapy does not worsen acute intracerebral hemorrhage in mice

Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy

Former of Turn Trajectory of Sliding Valve Shaft of Gas Line

Former of turn trajectory of sliding valve shaft of gas line, that allows to provide desired motion trajectory of sliding valve and its full closing, is considered in that paper. Imitation model of that former, research results, which allow to detect influence of gain factor and time constant of position controller on value of speed error, that has impact on delay of output coordinate from setting, and that results to delay of sliding valve motion process to setting position point, are shown