Metal interactions with neural substrates and their role in neurodegeneration
- Authors: Lack, Barbara Anne
- Date: 2003
- Subjects: Nervous system -- Degeneration Neurotoxicology Chemical reactions Metals -- Physiological effect Melatonin -- Physiological effect
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4391 , http://hdl.handle.net/10962/d1005709
- Description: "Life" may be characterized as a controlled stationary flow equilibrium, maintained by energy consuming chemical reactions. The physiological functioning of these life systems include at least 28 of the elements isolated on the periodic table thus far, most of which are metals. However, as with Paracelsus Principle: "The dose makes the poison", there exists a definite link between metal levels, essential and toxic, and the onset of neurodegenerative diseases. The economic costs of brain dysfunction are enormous, but this pales in comparison to the staggering emotional toll on the victims themselves and their families. In an attempt to improve the understanding of the causes of neurodegeneration, this study focuses on one potential aspect: the possible link between metals and neurotransmitter homeostasis utilising a variety of electronanalytical techniques. Adsorptive cathodic stripping voltammetry was employed to investigate the binding affinities and complex formation of melatonin and its precursor serotonin with calcium, potassium, sodium, lithium and aluminium. The results showed that all the metals studied formed complexes with both pineal indoleamines. However, the stability and affmity of the ligands toward the various metals varied greatly. The study suggests a further role for melatonin, that of metalloregulator and possible metal detoxifier in the brain, the in vivo studies which followed will further substantiate this notion. This research additionally focused on the cholinergic system, in particular acetylcholine complex formation studies with mercury, lead, cadmium, copper and zinc using the adsorptive cathodic stripping voltammetry method. The formation and characterisation of a solid mercury-acetylcholine complex lent further strength to the in situ electrochemical complex formation observed. The results showed the preference of acetylcholine for environmentally toxic heavy metals (such as Cd²⁺) over those divalent cations that occur naturally in the body. The possible metalloregulatory role melatonin played in the three brain regIOns: cerebellum, cortex and corpus striatum of male Wistar rats was studied as an in vivo extension of the earlier in vitro studies. Anodic stripping voltammetry was employed to detect metal levels present. The results showed that daily injections of melatonin was responsible for significantly decreasing copper(I), cadmium(II) and lead(II) levels in various regions of the rat brain of those animals that had undergone a pinealectomy in comparison to the saline injected group having undergone the same treatment. Histological and electrochemical stripping techniques were applied to investigate the implications of high A1³⁺ levels in the brain regions, particularly the hippocampus. Melatonin showed signs of promise in indirect symptom alleviation and by significantly decreasing A1³⁺ levels in rats that had been dosed with melatonin prior to A1³⁺ treatments in comparison with the control groups. Finally a preliminary study outlining a method for the production of a calcium selective microelectrode was undertaken. Further work is still needed to optimise the microelectrode production as well as its possible applications. However, whilst the overall conclusions of this entire multidisciplinary study may indeed only be in effect one piece of a very large puzzle on neurodegenerative diseases, this piece will no doubt serve as a building block for further ideas and work in this field.
- Full Text:
- Date Issued: 2003
- Authors: Lack, Barbara Anne
- Date: 2003
- Subjects: Nervous system -- Degeneration Neurotoxicology Chemical reactions Metals -- Physiological effect Melatonin -- Physiological effect
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4391 , http://hdl.handle.net/10962/d1005709
- Description: "Life" may be characterized as a controlled stationary flow equilibrium, maintained by energy consuming chemical reactions. The physiological functioning of these life systems include at least 28 of the elements isolated on the periodic table thus far, most of which are metals. However, as with Paracelsus Principle: "The dose makes the poison", there exists a definite link between metal levels, essential and toxic, and the onset of neurodegenerative diseases. The economic costs of brain dysfunction are enormous, but this pales in comparison to the staggering emotional toll on the victims themselves and their families. In an attempt to improve the understanding of the causes of neurodegeneration, this study focuses on one potential aspect: the possible link between metals and neurotransmitter homeostasis utilising a variety of electronanalytical techniques. Adsorptive cathodic stripping voltammetry was employed to investigate the binding affinities and complex formation of melatonin and its precursor serotonin with calcium, potassium, sodium, lithium and aluminium. The results showed that all the metals studied formed complexes with both pineal indoleamines. However, the stability and affmity of the ligands toward the various metals varied greatly. The study suggests a further role for melatonin, that of metalloregulator and possible metal detoxifier in the brain, the in vivo studies which followed will further substantiate this notion. This research additionally focused on the cholinergic system, in particular acetylcholine complex formation studies with mercury, lead, cadmium, copper and zinc using the adsorptive cathodic stripping voltammetry method. The formation and characterisation of a solid mercury-acetylcholine complex lent further strength to the in situ electrochemical complex formation observed. The results showed the preference of acetylcholine for environmentally toxic heavy metals (such as Cd²⁺) over those divalent cations that occur naturally in the body. The possible metalloregulatory role melatonin played in the three brain regIOns: cerebellum, cortex and corpus striatum of male Wistar rats was studied as an in vivo extension of the earlier in vitro studies. Anodic stripping voltammetry was employed to detect metal levels present. The results showed that daily injections of melatonin was responsible for significantly decreasing copper(I), cadmium(II) and lead(II) levels in various regions of the rat brain of those animals that had undergone a pinealectomy in comparison to the saline injected group having undergone the same treatment. Histological and electrochemical stripping techniques were applied to investigate the implications of high A1³⁺ levels in the brain regions, particularly the hippocampus. Melatonin showed signs of promise in indirect symptom alleviation and by significantly decreasing A1³⁺ levels in rats that had been dosed with melatonin prior to A1³⁺ treatments in comparison with the control groups. Finally a preliminary study outlining a method for the production of a calcium selective microelectrode was undertaken. Further work is still needed to optimise the microelectrode production as well as its possible applications. However, whilst the overall conclusions of this entire multidisciplinary study may indeed only be in effect one piece of a very large puzzle on neurodegenerative diseases, this piece will no doubt serve as a building block for further ideas and work in this field.
- Full Text:
- Date Issued: 2003
Electrochemical studies of gold bioaccumulation by yeast cell wall components
- Authors: Lack, Barbara Anne
- Date: 1999
- Subjects: Hydrometallurgy , Electrochemical analysis , Gold ores , Gold
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4311 , http://hdl.handle.net/10962/d1004969 , Hydrometallurgy , Electrochemical analysis , Gold ores , Gold
- Description: Gold, amongst other group 11 metals, was almost certainly one of the first three metals known to man. In addition to the economic importance of the metal, gold has a wide variety of applications in the medical, electrocatalytical and micro-electronics fields. However, the determination of gold ions in solution, with accuracy, precision, sensitivity and selectivity is still an interesting and much debated topic in analytical chemistry. A system whereby gold ions have been successfully detected employing an electrochemical technique, known as stripping voltammetry, has been developed. The electrochemical method was chosen over other available techniques for the sensitivity, particularly at low concentrations, and selectivity properties; notably in the presence of other metal ions. Under acidic conditions, the electrochemical technique was applied and the presence of gold(III), at a concentration of 2.53 x 10⁻⁵ mol dm⁻³ in a mine waste water sample, was detected. Biomass, in particular yeast and algal types, have been successfully employed in extracting low concentrations of gold ions from industrial effluents. The manipulation of the biological facility for mineral interaction, biohydrometallurgy, may yield numerous potential new technologies. South Africa in particular would benefit from this area of research, since the country is a major ore and metal refining country and if the output and the efficiency of the mines could be improved, even by a small percentage, the financial rewards would be vast. In this study, the application of adsorptive cathodic stripping voltammetry (AdCSV) of gold(III) in the presence of various Saccharomyces cerevisiae cell wall components, was investigated to determine which, if any, were involved specifically in the chemical binding of the gold ions. The chitin and mannan extracts showed the most promise with detection limits of 1.10 x 10⁻⁶ mol dm⁻³ and 9 x 10⁻⁹ mol dm⁻³, respectively; employing the AdCSV technique. A modification of the stripping voltammetry technique, Osteryoung square wave stripping voltammetry (OSWSV), provided the lowest detection limit, for gold(IIl) in the presence of mannan, of 1.70 x 10⁻¹¹ mol dm⁻³ ; utilising a modified carbon paste electrode. The detection of gold(III) has been shown to be dependent on the type of electrode employed, the electrolyte solution and the presence of interfering agents. The effect of copper(II) and silver(I) on the detection of the gold(III) in solution was investigated; whilst the silver(I) has shown no detrimental effects on gold (III) detection systems, copper(II) has indicated the possibility of forming an inter-metallic compound with the gold(III). However, mannan has shown to selectively and preferentially bind the gold(III) in the presence of a ten-fold excess of copper(II). Nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy, as well as computer modelling techniques were employed to further investIgate the mannan-gold(III) interaction and proposed complex formed. The NMR, IR and computer modelling data are in agreement with the electrochemical data on proposing a mannan-gold(III) complex. The co-ordination site was established to be in the vicinity of the H-I and H-2 protons and the gold(III) adopts a square-planar geometry upon co-ordination. The benefits of the research are useful from a biological perspective (i. e. as more is known about the binding sites, microbiologists/biochemists may work on the optimisation of parameters for these sites or work could be furthered into the enhanced expression of the sites) and an industrial one. In addition to the' two major benefits, an improved understanding of gold and its chemistry would be achieved, which is advantageous for other fields of research as well.
- Full Text:
- Date Issued: 1999
- Authors: Lack, Barbara Anne
- Date: 1999
- Subjects: Hydrometallurgy , Electrochemical analysis , Gold ores , Gold
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4311 , http://hdl.handle.net/10962/d1004969 , Hydrometallurgy , Electrochemical analysis , Gold ores , Gold
- Description: Gold, amongst other group 11 metals, was almost certainly one of the first three metals known to man. In addition to the economic importance of the metal, gold has a wide variety of applications in the medical, electrocatalytical and micro-electronics fields. However, the determination of gold ions in solution, with accuracy, precision, sensitivity and selectivity is still an interesting and much debated topic in analytical chemistry. A system whereby gold ions have been successfully detected employing an electrochemical technique, known as stripping voltammetry, has been developed. The electrochemical method was chosen over other available techniques for the sensitivity, particularly at low concentrations, and selectivity properties; notably in the presence of other metal ions. Under acidic conditions, the electrochemical technique was applied and the presence of gold(III), at a concentration of 2.53 x 10⁻⁵ mol dm⁻³ in a mine waste water sample, was detected. Biomass, in particular yeast and algal types, have been successfully employed in extracting low concentrations of gold ions from industrial effluents. The manipulation of the biological facility for mineral interaction, biohydrometallurgy, may yield numerous potential new technologies. South Africa in particular would benefit from this area of research, since the country is a major ore and metal refining country and if the output and the efficiency of the mines could be improved, even by a small percentage, the financial rewards would be vast. In this study, the application of adsorptive cathodic stripping voltammetry (AdCSV) of gold(III) in the presence of various Saccharomyces cerevisiae cell wall components, was investigated to determine which, if any, were involved specifically in the chemical binding of the gold ions. The chitin and mannan extracts showed the most promise with detection limits of 1.10 x 10⁻⁶ mol dm⁻³ and 9 x 10⁻⁹ mol dm⁻³, respectively; employing the AdCSV technique. A modification of the stripping voltammetry technique, Osteryoung square wave stripping voltammetry (OSWSV), provided the lowest detection limit, for gold(IIl) in the presence of mannan, of 1.70 x 10⁻¹¹ mol dm⁻³ ; utilising a modified carbon paste electrode. The detection of gold(III) has been shown to be dependent on the type of electrode employed, the electrolyte solution and the presence of interfering agents. The effect of copper(II) and silver(I) on the detection of the gold(III) in solution was investigated; whilst the silver(I) has shown no detrimental effects on gold (III) detection systems, copper(II) has indicated the possibility of forming an inter-metallic compound with the gold(III). However, mannan has shown to selectively and preferentially bind the gold(III) in the presence of a ten-fold excess of copper(II). Nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy, as well as computer modelling techniques were employed to further investIgate the mannan-gold(III) interaction and proposed complex formed. The NMR, IR and computer modelling data are in agreement with the electrochemical data on proposing a mannan-gold(III) complex. The co-ordination site was established to be in the vicinity of the H-I and H-2 protons and the gold(III) adopts a square-planar geometry upon co-ordination. The benefits of the research are useful from a biological perspective (i. e. as more is known about the binding sites, microbiologists/biochemists may work on the optimisation of parameters for these sites or work could be furthered into the enhanced expression of the sites) and an industrial one. In addition to the' two major benefits, an improved understanding of gold and its chemistry would be achieved, which is advantageous for other fields of research as well.
- Full Text:
- Date Issued: 1999
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