The impact of the BBB-EE policy instrument on wealth inequality : A case study on the banking sector of South Africa
- Moshikaro, Kei Kgaogelo Felia
- Authors: Moshikaro, Kei Kgaogelo Felia
- Date: 2021-10
- Subjects: Black Economic Empowerment (Program : South Africa) , Income distribution South Africa , South Africa Economic policy , South Africa Economic conditions 1991- , Banks and banking South Africa , South Africa. Financial Sector Regulation Act, 2017
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/191035 , vital:45052
- Description: It has been recognised that, whether measured in terms of income or wealth, South Africa remains as one of the most unequal societies in the world. Reducing these high levels of inequalities has been an important area of focus through the formulation of policy instruments by South African policy makers. Within a specific focus on the South African banking sector, the objective of this research is to ascertaining the extent to which addressing inequalities was in fact achieved through the changing of wealth ownerships under the Broad Based Black Economic Empowerment policy instrument. To contextualise, the thesis surveys literature on two stylised economic hypotheses on both income and wealth to understand the potential causes of their respective inequalities. An exploration of both income, wealth measurements and their distributions in South Africa are presented, in addition to policy instruments designed to ameliorate income and wealth inequalities in South Africa. The thesis further presents brief case studies from the literature on Brazil’s success in reducing its high income inequality and the Malaysian National Economic Policy empowerment program to effect wealth economic transformation, as comparatives to the South African experience. The thesis findings indicate that contrary to the objectives of the BBB-EE instrument and wealth transfers, the program within the banking sector resulted in highly unequal wealth shares and equally high concentration levels. The richest top one per cent of individuals participating in the BEE transactions in the banking sector captured 79 per cent of the total wealth transfers, this providing indications of extremely high concentrations of wealth. Further, wealth meaningfully cumulates at only the 50 percentage level of the wealth distribution, this additionally suggesting that wealth transfers featured less in the bottom half of the wealth distribution. The banking BBB-EE wealth Gini coefficient of 0.88 is evidence of the extremely high levels of inequality that resulted from the BBB-EE program within the banking sector. , Thesis (MCom) -- Faculty of Commerce, Economics and Economic History, 2021
- Full Text:
- Authors: Moshikaro, Kei Kgaogelo Felia
- Date: 2021-10
- Subjects: Black Economic Empowerment (Program : South Africa) , Income distribution South Africa , South Africa Economic policy , South Africa Economic conditions 1991- , Banks and banking South Africa , South Africa. Financial Sector Regulation Act, 2017
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/191035 , vital:45052
- Description: It has been recognised that, whether measured in terms of income or wealth, South Africa remains as one of the most unequal societies in the world. Reducing these high levels of inequalities has been an important area of focus through the formulation of policy instruments by South African policy makers. Within a specific focus on the South African banking sector, the objective of this research is to ascertaining the extent to which addressing inequalities was in fact achieved through the changing of wealth ownerships under the Broad Based Black Economic Empowerment policy instrument. To contextualise, the thesis surveys literature on two stylised economic hypotheses on both income and wealth to understand the potential causes of their respective inequalities. An exploration of both income, wealth measurements and their distributions in South Africa are presented, in addition to policy instruments designed to ameliorate income and wealth inequalities in South Africa. The thesis further presents brief case studies from the literature on Brazil’s success in reducing its high income inequality and the Malaysian National Economic Policy empowerment program to effect wealth economic transformation, as comparatives to the South African experience. The thesis findings indicate that contrary to the objectives of the BBB-EE instrument and wealth transfers, the program within the banking sector resulted in highly unequal wealth shares and equally high concentration levels. The richest top one per cent of individuals participating in the BEE transactions in the banking sector captured 79 per cent of the total wealth transfers, this providing indications of extremely high concentrations of wealth. Further, wealth meaningfully cumulates at only the 50 percentage level of the wealth distribution, this additionally suggesting that wealth transfers featured less in the bottom half of the wealth distribution. The banking BBB-EE wealth Gini coefficient of 0.88 is evidence of the extremely high levels of inequality that resulted from the BBB-EE program within the banking sector. , Thesis (MCom) -- Faculty of Commerce, Economics and Economic History, 2021
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The physical activity status and the impact of lifestyle behaviours on workplace productivity and absenteeism of Transnet employees
- Authors: Zimmermann, Sharnae Vanessa
- Date: 2021-10
- Subjects: Transnet (Firm : South Africa) Employees , Absenteeism (Labor) South Africa Durban , Labor productivity South Africa Durban , Exercise , Sedentary behavior , Lifestyles
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/190077 , vital:44961
- Description: Increased sitting time, insufficient physical activity and sub-optimal body composition are all contributing to the global disease burden. This is made evident by increases in obesity, type II diabetes, cardiovascular diseases (i.e. hypertension and strokes), cancer and other non-communicable diseases resulting in absenteeism and reduced productivity in the workplace. The global rise in sitting time and physical inactivity is caused, in part, by changes in transport convenience, work roles and technological advancements. Employees working in office environments or driving trains sit for prolonged periods; something which is evident in the industry that Transnet operates in. Sitting time and physical inactivity are independent risk factors for non-communicable diseases with poor nutrition, smoking, alcohol consumption and psychological wellbeing, being separate constructs. The purpose of the study is to determine the levels of sedentary behaviour, physical inactivity, obesity, nutrition, alcohol consumption, smoking, non-communicable disease risk, mental wellbeing and their association with productivity and absenteeism in office workers and train drivers at Transnet Freight Rail, Durban. A cross-sectional study was done with 40 participants, 20 office workers and 20 train drivers. Stature (175.80 ± 9.43 ±cm) and body mass (83.85 ± 20.31 kg) were measured; and body mass index calculated (26.98 ± 5.37 kg.m2). Physical activity levels, sedentary behaviour, body mass index and other lifestyle factors were explored using an amended version of The Health and Wellbeing survey, a self-report measure. The results revealed that there was a high prevalence of sedentary behaviour (train drivers = 7.85 ± 2.21 and office workers = 8.3 ± 1.03), particularly among office workers. Most of the participants had a relatively high body mass index, placing in the overweight and obese category, particularly among train drivers. The prevalence of physical inactivity was marginally higher for office workers compared to train drivers. There were significantly (p<0.05) higher levels of physical activity within train drivers with a moderate effect size. There were limited associations found between lifestyle factors and sickness absenteeism and worker productivity. Obesity had the most prominent relationship with noncommunicable diseases, followed by high levels of sedentary behaviour, not meeting physical activity guidelines, obesity, overweight, and prolonged sitting time at work. A significant and moderate correlation was found between obesity and absenteeism (train drivers: r = 0.32 and office workers: r= 0.46), however, no associations were found between sedentary behaviour, physical activity and fruit and vegetable intake and absenteeism. Lastly, the association between physical activity and productivity among the train drivers was low negative (r=-0.15) which was not significant (p>0.05). The associations between physical activity and productivity among office workers, however, was both significant (p<0.05) and moderate positive (r=0.39). The vegetable intake among the office workers showed a significant (p<0.05) moderate positive association with productivity (r=0.49). The association between vegetable intake and productivity among the train drivers was not significant (p>0.05) and low positive (r=0.16). There was a significant (p<0.05) and moderate positive association between fruit intake and productivity among both train drivers (r=0.43) and office workers (r=0.47). No significant associations between sedentary behaviour and obesity and productivity were found. The current study provided new insight into the risks associated with lifestyle factors of office workers and train drivers in the transportation sector. The poor lifestyle factors, together with the high prevalence of sedentary behaviour and physical inactivity, provide ideal opportunities for future interventions to focus on workers productivity and overall wellbeing. The job design of train drivers and office workers does not place significant importance on employee health and wellness. Essentially they are not “healthy” but they work productively, giving reason as to why employee wellness is not a priority for employers. The current findings of the study suggest that adopting regular physical activity, healthy dietary patterns and reduced sitting time should be promoted as key components of lifestyle interventions for the prevention of non-communicable diseases in office workers and train drivers. , Thesis (MSc) -- Faculty of Science, Human Kinetics and Ergonomics, 2021
- Full Text:
- Authors: Zimmermann, Sharnae Vanessa
- Date: 2021-10
- Subjects: Transnet (Firm : South Africa) Employees , Absenteeism (Labor) South Africa Durban , Labor productivity South Africa Durban , Exercise , Sedentary behavior , Lifestyles
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/190077 , vital:44961
- Description: Increased sitting time, insufficient physical activity and sub-optimal body composition are all contributing to the global disease burden. This is made evident by increases in obesity, type II diabetes, cardiovascular diseases (i.e. hypertension and strokes), cancer and other non-communicable diseases resulting in absenteeism and reduced productivity in the workplace. The global rise in sitting time and physical inactivity is caused, in part, by changes in transport convenience, work roles and technological advancements. Employees working in office environments or driving trains sit for prolonged periods; something which is evident in the industry that Transnet operates in. Sitting time and physical inactivity are independent risk factors for non-communicable diseases with poor nutrition, smoking, alcohol consumption and psychological wellbeing, being separate constructs. The purpose of the study is to determine the levels of sedentary behaviour, physical inactivity, obesity, nutrition, alcohol consumption, smoking, non-communicable disease risk, mental wellbeing and their association with productivity and absenteeism in office workers and train drivers at Transnet Freight Rail, Durban. A cross-sectional study was done with 40 participants, 20 office workers and 20 train drivers. Stature (175.80 ± 9.43 ±cm) and body mass (83.85 ± 20.31 kg) were measured; and body mass index calculated (26.98 ± 5.37 kg.m2). Physical activity levels, sedentary behaviour, body mass index and other lifestyle factors were explored using an amended version of The Health and Wellbeing survey, a self-report measure. The results revealed that there was a high prevalence of sedentary behaviour (train drivers = 7.85 ± 2.21 and office workers = 8.3 ± 1.03), particularly among office workers. Most of the participants had a relatively high body mass index, placing in the overweight and obese category, particularly among train drivers. The prevalence of physical inactivity was marginally higher for office workers compared to train drivers. There were significantly (p<0.05) higher levels of physical activity within train drivers with a moderate effect size. There were limited associations found between lifestyle factors and sickness absenteeism and worker productivity. Obesity had the most prominent relationship with noncommunicable diseases, followed by high levels of sedentary behaviour, not meeting physical activity guidelines, obesity, overweight, and prolonged sitting time at work. A significant and moderate correlation was found between obesity and absenteeism (train drivers: r = 0.32 and office workers: r= 0.46), however, no associations were found between sedentary behaviour, physical activity and fruit and vegetable intake and absenteeism. Lastly, the association between physical activity and productivity among the train drivers was low negative (r=-0.15) which was not significant (p>0.05). The associations between physical activity and productivity among office workers, however, was both significant (p<0.05) and moderate positive (r=0.39). The vegetable intake among the office workers showed a significant (p<0.05) moderate positive association with productivity (r=0.49). The association between vegetable intake and productivity among the train drivers was not significant (p>0.05) and low positive (r=0.16). There was a significant (p<0.05) and moderate positive association between fruit intake and productivity among both train drivers (r=0.43) and office workers (r=0.47). No significant associations between sedentary behaviour and obesity and productivity were found. The current study provided new insight into the risks associated with lifestyle factors of office workers and train drivers in the transportation sector. The poor lifestyle factors, together with the high prevalence of sedentary behaviour and physical inactivity, provide ideal opportunities for future interventions to focus on workers productivity and overall wellbeing. The job design of train drivers and office workers does not place significant importance on employee health and wellness. Essentially they are not “healthy” but they work productively, giving reason as to why employee wellness is not a priority for employers. The current findings of the study suggest that adopting regular physical activity, healthy dietary patterns and reduced sitting time should be promoted as key components of lifestyle interventions for the prevention of non-communicable diseases in office workers and train drivers. , Thesis (MSc) -- Faculty of Science, Human Kinetics and Ergonomics, 2021
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The tuber-feeding weevil Listronotus frontalis as a candidate biological control agent for the invasive semi-aquatic plant Sagittaria platyphylla within South Africa
- Authors: Rogers, Daniel James
- Date: 2021-10
- Subjects: Listronotus South Africa , Arrowhead (Plants) South Africa , Arrowhead (Plants) Biological control South Africa , Invasive plants Biological control South Africa , Insects as biological pest control agents South Africa , Plant populations South Africa
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/190731 , vital:45023
- Description: Sagittaria platyphylla (Engelm.) J.G.Sm. (Alismataceae) is an invasive, aquatic macrophyte originating in the southern United States of America. In South Africa, the plant was first detected in Krantzkloof Nature Reserve, KwaZulu-Natal Province in 2008, and due to its known impact in other countries, it was listed as a Category 1a invader species under the National Environmental Management: Biodiversity Act 2004 (NEM:BA). This invasive plant has proved difficult to manage due to its varied growth forms and reproductive strategies, such as prolific seed and below ground tuber production. Due to the limitations of conventional control mechanisms, biological control is currently being considered as a potential control option. The tuber feeding weevil Listronotus frontalis LeConte (Coleoptera: Curculionidae) has been identified as a candidate biological control agent for this invasive species. The aims of this study were twofold; to firstly determine the importance of tubers to S. platyphylla populations growing in South Africa; and secondly, to determine the biology and suitability of L. frontalis, a tuber feeder, as a candidate biological control agent. Surveys of S. platyphylla populations in South Africa showed that tubers were found in all sampled sites, except for Krantzkloof Nature reserve in KwaZulu-Natal Province. The highest number of tubers was 97.75 ± 10.62 (SE) m-2 recorded at Jonkershoek in the Western Cape Province. Monthly sampling from two sites in the Eastern Cape Province, the Makana Botanical Gardens and Maden Dam showed that neither season nor water depth affected tuber production. However, the mean number of tubers as well as mass of tubers sampled, were consistently higher (F(1,179) = 20.9542, P < 0.0001) and heavier (F(1, 857) = 585.7293, P < 0.0001) at the Botanical Gardens than at Maden Dam, respectively. The study showed that tubers are an important life stage of S. platyphylla populations and may vary in size and abundance between and within sites. The tuber feeding weevil was shown to develop from egg to ovipositing adult within just over 40 days. Females were recorded to lay up to 48 eggs within a period of one week. Impact studies showed that adult feeding led to a reduction in all but one of the 11 measured plant growth and developmental measurements, including a reduction in the mean mass of the above-ground plant material (F(2,2743) = 12.05, P = 0.002) as well as a reduction in size and abundance of tubers (F(2,58.47) = 9.756, P = 0.0006) and stolons(F(14.943) = 8.7577, P = 0.003). These results are encouraging and suggest that if the insect is released in South Africa, it may prove to be a valuable biocontrol agent. It is concluded that, until suitable biological control options become available in South Africa, the chemical and mechanical control measures currently implemented should continue, however, controlling tubers should be considered during the planning and implementation of these strategies. , Thesis (MSc) -- Faculty of Science, Zoology and Entomology, 2021
- Full Text:
- Authors: Rogers, Daniel James
- Date: 2021-10
- Subjects: Listronotus South Africa , Arrowhead (Plants) South Africa , Arrowhead (Plants) Biological control South Africa , Invasive plants Biological control South Africa , Insects as biological pest control agents South Africa , Plant populations South Africa
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/190731 , vital:45023
- Description: Sagittaria platyphylla (Engelm.) J.G.Sm. (Alismataceae) is an invasive, aquatic macrophyte originating in the southern United States of America. In South Africa, the plant was first detected in Krantzkloof Nature Reserve, KwaZulu-Natal Province in 2008, and due to its known impact in other countries, it was listed as a Category 1a invader species under the National Environmental Management: Biodiversity Act 2004 (NEM:BA). This invasive plant has proved difficult to manage due to its varied growth forms and reproductive strategies, such as prolific seed and below ground tuber production. Due to the limitations of conventional control mechanisms, biological control is currently being considered as a potential control option. The tuber feeding weevil Listronotus frontalis LeConte (Coleoptera: Curculionidae) has been identified as a candidate biological control agent for this invasive species. The aims of this study were twofold; to firstly determine the importance of tubers to S. platyphylla populations growing in South Africa; and secondly, to determine the biology and suitability of L. frontalis, a tuber feeder, as a candidate biological control agent. Surveys of S. platyphylla populations in South Africa showed that tubers were found in all sampled sites, except for Krantzkloof Nature reserve in KwaZulu-Natal Province. The highest number of tubers was 97.75 ± 10.62 (SE) m-2 recorded at Jonkershoek in the Western Cape Province. Monthly sampling from two sites in the Eastern Cape Province, the Makana Botanical Gardens and Maden Dam showed that neither season nor water depth affected tuber production. However, the mean number of tubers as well as mass of tubers sampled, were consistently higher (F(1,179) = 20.9542, P < 0.0001) and heavier (F(1, 857) = 585.7293, P < 0.0001) at the Botanical Gardens than at Maden Dam, respectively. The study showed that tubers are an important life stage of S. platyphylla populations and may vary in size and abundance between and within sites. The tuber feeding weevil was shown to develop from egg to ovipositing adult within just over 40 days. Females were recorded to lay up to 48 eggs within a period of one week. Impact studies showed that adult feeding led to a reduction in all but one of the 11 measured plant growth and developmental measurements, including a reduction in the mean mass of the above-ground plant material (F(2,2743) = 12.05, P = 0.002) as well as a reduction in size and abundance of tubers (F(2,58.47) = 9.756, P = 0.0006) and stolons(F(14.943) = 8.7577, P = 0.003). These results are encouraging and suggest that if the insect is released in South Africa, it may prove to be a valuable biocontrol agent. It is concluded that, until suitable biological control options become available in South Africa, the chemical and mechanical control measures currently implemented should continue, however, controlling tubers should be considered during the planning and implementation of these strategies. , Thesis (MSc) -- Faculty of Science, Zoology and Entomology, 2021
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Gender bias in the field of economics: an analysis of South African academia
- Authors: Hitchcock, Siobhan
- Date: 2020-10-30
- Subjects: Sexism South Africa , Sexism in higher education South Africa , Economics Study and teaching (Higher) South Africa , Economics teachers South Africa , Women in higher education South Africa
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/366275 , vital:65850
- Description: In recent years there has been a growing focus internationally on the low participation of females in Economics, both in academia and business. While female enrolment in higher education, including other maths-based subjects, has grown substantially, this has not been the case for Economics. Economics, particularly as one progresses through postgraduate studies to doctoral degrees now stands out as an outlier. A number of reasons have been advanced for this, including the nature of the subject, the type of people it attracts and the lack of female role models. Male and female enrolments in South African HEIs have grown between 2007 and 2017, but females have grown at a faster rate, thus increasing the female share of total enrolments to 59%. Female students are more successful and so make up an even greater proportion of South African graduates. Female enrolments and graduates are also higher than in the US. As in the US there is a significant drop off in female representation when progressing from undergraduate to postgraduate studies in South Africa. When looking at Economics in South Africa in comparison to the broad CESM categories, female enrolment in Economics Bachelor degrees is significantly lower than in Business and Humanities, but on a par with STEM subjects. At the Doctoral level, there are sharp drop offs in female enrolments for all categories. Business and Economics are the laggards at the Doctoral level, below STEM and Humanities. Furthermore, females make up a minority of academic staff in South African HEIs, with males dominating in especially the higher academic ranks. As one moves up the academic ladder, the female share decreases. This research analyses gender compositions of staff and students at South African HEIs. National data are obtained from government publications and data relating to four specific South African universities was obtained directly from the universities. Questionnaires were sent to a sample of academic staff and students who are in the field of economics to identify whether there is a role model effect for economics students and whether female academics experience the same forms of biases, discrimination, or treatment as that identified in international studies. It was concluded that while there are drop offs in the overall female representation of students at the Masters and Doctoral levels in South Africa, this share is gradually increasing. Additionally, Economics seems to perform better than what is depicted in the US, and in comparison to some STEM subjects in South Africa. Furthermore, the environment within the field of academic economics for both female students and staff seems to be more positive than what the international literature depicts for the US. But there are nonetheless different levels of satisfaction between male and female academic economists. While the student surveys revealed that female Economics students do not attach great importance to female role models, there is some evidence of correlation between the percentage of female professors and the percentage of female PhD students across a range of STEM subjects in South Africa. , Thesis (MCom) -- Faculty of Commerce, Economics and Economic History, 2020
- Full Text:
- Authors: Hitchcock, Siobhan
- Date: 2020-10-30
- Subjects: Sexism South Africa , Sexism in higher education South Africa , Economics Study and teaching (Higher) South Africa , Economics teachers South Africa , Women in higher education South Africa
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/366275 , vital:65850
- Description: In recent years there has been a growing focus internationally on the low participation of females in Economics, both in academia and business. While female enrolment in higher education, including other maths-based subjects, has grown substantially, this has not been the case for Economics. Economics, particularly as one progresses through postgraduate studies to doctoral degrees now stands out as an outlier. A number of reasons have been advanced for this, including the nature of the subject, the type of people it attracts and the lack of female role models. Male and female enrolments in South African HEIs have grown between 2007 and 2017, but females have grown at a faster rate, thus increasing the female share of total enrolments to 59%. Female students are more successful and so make up an even greater proportion of South African graduates. Female enrolments and graduates are also higher than in the US. As in the US there is a significant drop off in female representation when progressing from undergraduate to postgraduate studies in South Africa. When looking at Economics in South Africa in comparison to the broad CESM categories, female enrolment in Economics Bachelor degrees is significantly lower than in Business and Humanities, but on a par with STEM subjects. At the Doctoral level, there are sharp drop offs in female enrolments for all categories. Business and Economics are the laggards at the Doctoral level, below STEM and Humanities. Furthermore, females make up a minority of academic staff in South African HEIs, with males dominating in especially the higher academic ranks. As one moves up the academic ladder, the female share decreases. This research analyses gender compositions of staff and students at South African HEIs. National data are obtained from government publications and data relating to four specific South African universities was obtained directly from the universities. Questionnaires were sent to a sample of academic staff and students who are in the field of economics to identify whether there is a role model effect for economics students and whether female academics experience the same forms of biases, discrimination, or treatment as that identified in international studies. It was concluded that while there are drop offs in the overall female representation of students at the Masters and Doctoral levels in South Africa, this share is gradually increasing. Additionally, Economics seems to perform better than what is depicted in the US, and in comparison to some STEM subjects in South Africa. Furthermore, the environment within the field of academic economics for both female students and staff seems to be more positive than what the international literature depicts for the US. But there are nonetheless different levels of satisfaction between male and female academic economists. While the student surveys revealed that female Economics students do not attach great importance to female role models, there is some evidence of correlation between the percentage of female professors and the percentage of female PhD students across a range of STEM subjects in South Africa. , Thesis (MCom) -- Faculty of Commerce, Economics and Economic History, 2020
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Determination of speaker configuration for an immersive audio content creation system
- Authors: Lebusa, Motebang
- Date: 2020
- Subjects: Loudspeakers , Surround-sound systems , Algorithms , Coordinates
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/163375 , vital:41034
- Description: Various spatialisation algorithms require the knowledge of speaker locations to accurately localise sound in 3D environments. The rendering process uses speaker coordinates to feed into their algorithms so that they can render the immersive audio content as intended by an artist. The need to measure the loudspeaker coordinates becomes necessary, especially in environments where the speaker layouts change frequently. Manually measuring the coordinates, however, tends to be a laborious task that is prone to errors. This research provides an automated solution to the problem of speaker coordinates measurement. The solution system, SDIAS, is a client-server system that uses the capabilities provided by the Ethernet Audio Video Bridging standard to measure the 3D loudspeaker coordinates for immersive sound systems. SDIAS deploys commodity hardware and readily available software to implement the solution. A server sends a short tone to each speaker in the speaker configuration, at equal intervals. A microphone attached to a mobile device picks up these transmitted tones on the client side, from different locations. The transmission and reception times from both components of the system are used to measure the time of flight for each tone sent to a loudspeaker. These are then used to determine the 3D coordinates of each loudspeaker in the available layout. Tests were performed to determine the accuracy of the determination algorithm for SDIAS, and were compared to the manually measured coordinates. , Thesis (MSc) -- Faculty of Science, Computer Science, 2020
- Full Text:
- Authors: Lebusa, Motebang
- Date: 2020
- Subjects: Loudspeakers , Surround-sound systems , Algorithms , Coordinates
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/163375 , vital:41034
- Description: Various spatialisation algorithms require the knowledge of speaker locations to accurately localise sound in 3D environments. The rendering process uses speaker coordinates to feed into their algorithms so that they can render the immersive audio content as intended by an artist. The need to measure the loudspeaker coordinates becomes necessary, especially in environments where the speaker layouts change frequently. Manually measuring the coordinates, however, tends to be a laborious task that is prone to errors. This research provides an automated solution to the problem of speaker coordinates measurement. The solution system, SDIAS, is a client-server system that uses the capabilities provided by the Ethernet Audio Video Bridging standard to measure the 3D loudspeaker coordinates for immersive sound systems. SDIAS deploys commodity hardware and readily available software to implement the solution. A server sends a short tone to each speaker in the speaker configuration, at equal intervals. A microphone attached to a mobile device picks up these transmitted tones on the client side, from different locations. The transmission and reception times from both components of the system are used to measure the time of flight for each tone sent to a loudspeaker. These are then used to determine the 3D coordinates of each loudspeaker in the available layout. Tests were performed to determine the accuracy of the determination algorithm for SDIAS, and were compared to the manually measured coordinates. , Thesis (MSc) -- Faculty of Science, Computer Science, 2020
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Investigating cannabinoids and endocannabinoid receptors as drug targets for pain and inflammation
- Authors: Marwarwa, Sinobomi Zamachi
- Date: 2020
- Subjects: Cannabinoids , Cannabinoids Receptors , Inflammation Alternative treatment , Pain Alternative treatment , Drug targeting
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/164468 , vital:41121
- Description: Cannabinoids and the endocannabinoid system have been studied in the past decades but have yet to be fully understood. An insight into interactions that occur between cannabinoid compounds and their receptors is important for understanding the cannabinoids and the endocannabinoid system. Cannabinoids are natural products found in some cannabis plants, and they have similar effects to endocannabinoids, which are chemicals in the body that are involved many aspects of health from appetite, memory, and movement to pain, inflammation and response to cancer. Cannabinoids have a high impact on the treatment of pain and inflammation, they show different antinociceptive mechanisms to existing drugs like opioids, also, they have antimigraine properties better than those achieved by aspirin. The CB1 and CB2 human receptors have been the most studied cannabinoid receptors. In this project, we used a combination of mass-spectrometry to generate plausible chemical fragments and computational techniques to assess the binding of these fragments to these two main CB receptors. CB1 was adapted from the protein data bank (PBD), file 5U09 and the CB2 model was predicted using the hierarchical protocol I-TASSER, starting from the amino acid sequence in UniProt (P34972 CNR2_HUMAN). The proposed active site for CB1 was reported in a publication accompanying the 5U09 PDB model, which was originally generated with a pre-existing ligand in the active site. However, CB2 had to be built from a homology model and the active site determined using a combination of I-TASSER, Maestro, and CASTp the more favourable binding energies were determined by CASTp, leading to the use of the CASTp coordinates as default for docking in the CB2 human receptor. The molecular docking of cannabinoids THC, CBD, CBDV, CBG and CBN on both the CB1 and CB2 proteins was performed to identify the amino acids that interact with these compounds at their active sites. This would provide a guide to a future fragment-based drug discovery (FBDD) synthesis project. The docking in this work showed adequate accuracy with binding energies between -8.23 kcal/mol and -9.97 kcal/mol for CB1 and between -6.78 kcal/mol and -7.74 kcal/mol for CB2. An observation made was that binding energies of the CB1 human receptor docking were higher than those of the CB2 human receptor, which could support the widely held belief that CB1 is more important in cannabinoid interactions. The cannabinoids were then subjected to collision-induced dissociation to produce fragment structures predicted in chapter 2. These hypothetical fragments were docked in the CB1 and CB2 human receptor, the general trend again being the binding energies for the CB1 receptor was again around 10% higher than those of the CB2 receptor. As expected, larger fragments tended to have better binding, with the fragment proposed from m/z 259 with binding energies -9.62 kcal/mol in CB1 and -6.26 kcal/mol. Those fragments with significant lipophilic side chains or some aromatic moiety also showed good binding or around -6.00 kcal/mol, similar to the intact cannabinoids. In our case, this fragment was proposed from m/z 223 with binding energies -7.71 kcal/mol in CB1 and -6.5 kcal/mol in CB2. The results from the fragment dockings were favourable in that they have binding affinities lower than -6.0 kcal/mol which is good enough for the structures to be leads in the creation of fragment libraries. The docking was performed with Autodock 1.5.6 and data visualization with a discovery studio. , Thesis (MSc) -- Faculty of Science, Chemistry, 2020
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- Authors: Marwarwa, Sinobomi Zamachi
- Date: 2020
- Subjects: Cannabinoids , Cannabinoids Receptors , Inflammation Alternative treatment , Pain Alternative treatment , Drug targeting
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/164468 , vital:41121
- Description: Cannabinoids and the endocannabinoid system have been studied in the past decades but have yet to be fully understood. An insight into interactions that occur between cannabinoid compounds and their receptors is important for understanding the cannabinoids and the endocannabinoid system. Cannabinoids are natural products found in some cannabis plants, and they have similar effects to endocannabinoids, which are chemicals in the body that are involved many aspects of health from appetite, memory, and movement to pain, inflammation and response to cancer. Cannabinoids have a high impact on the treatment of pain and inflammation, they show different antinociceptive mechanisms to existing drugs like opioids, also, they have antimigraine properties better than those achieved by aspirin. The CB1 and CB2 human receptors have been the most studied cannabinoid receptors. In this project, we used a combination of mass-spectrometry to generate plausible chemical fragments and computational techniques to assess the binding of these fragments to these two main CB receptors. CB1 was adapted from the protein data bank (PBD), file 5U09 and the CB2 model was predicted using the hierarchical protocol I-TASSER, starting from the amino acid sequence in UniProt (P34972 CNR2_HUMAN). The proposed active site for CB1 was reported in a publication accompanying the 5U09 PDB model, which was originally generated with a pre-existing ligand in the active site. However, CB2 had to be built from a homology model and the active site determined using a combination of I-TASSER, Maestro, and CASTp the more favourable binding energies were determined by CASTp, leading to the use of the CASTp coordinates as default for docking in the CB2 human receptor. The molecular docking of cannabinoids THC, CBD, CBDV, CBG and CBN on both the CB1 and CB2 proteins was performed to identify the amino acids that interact with these compounds at their active sites. This would provide a guide to a future fragment-based drug discovery (FBDD) synthesis project. The docking in this work showed adequate accuracy with binding energies between -8.23 kcal/mol and -9.97 kcal/mol for CB1 and between -6.78 kcal/mol and -7.74 kcal/mol for CB2. An observation made was that binding energies of the CB1 human receptor docking were higher than those of the CB2 human receptor, which could support the widely held belief that CB1 is more important in cannabinoid interactions. The cannabinoids were then subjected to collision-induced dissociation to produce fragment structures predicted in chapter 2. These hypothetical fragments were docked in the CB1 and CB2 human receptor, the general trend again being the binding energies for the CB1 receptor was again around 10% higher than those of the CB2 receptor. As expected, larger fragments tended to have better binding, with the fragment proposed from m/z 259 with binding energies -9.62 kcal/mol in CB1 and -6.26 kcal/mol. Those fragments with significant lipophilic side chains or some aromatic moiety also showed good binding or around -6.00 kcal/mol, similar to the intact cannabinoids. In our case, this fragment was proposed from m/z 223 with binding energies -7.71 kcal/mol in CB1 and -6.5 kcal/mol in CB2. The results from the fragment dockings were favourable in that they have binding affinities lower than -6.0 kcal/mol which is good enough for the structures to be leads in the creation of fragment libraries. The docking was performed with Autodock 1.5.6 and data visualization with a discovery studio. , Thesis (MSc) -- Faculty of Science, Chemistry, 2020
- Full Text:
Synthesis and in vitro biological evaluation of 2,3-substituted quinoline derivatives
- Bokosi, Fostino Raphael Bentry
- Authors: Bokosi, Fostino Raphael Bentry
- Date: 2020
- Subjects: Quinoline , Malaria Chemotherapy , Tuberculosis Chemotherapy , African trypanosomiasis Chemotherapy
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/163193 , vital:41017
- Description: The urgent need for new systemic pharmacological entities prompted us to report a library of 2,3-substituted quinoline derivatives. Considering the ubiquity of quinoline-containing compounds in pharmacologically active small molecules, synthesized 2,3-substituted quinoline derivatives were in vitro biologically evaluated for their potential antitubercular, antimalarial and antitrypanosomal activities. Quinoline scaffold was achieved by the Vilsmeier-Haack methodology, affording synthetically useful chloro and formyl substituents on C-2 and C-3 respectively. These two substituents acted as handles in expanding the chemical space around the quinoline ring. Target compounds were synthesized in six to seven steps, employing conventional synthetic organic protocols adapted from various literature. The final compounds were accessed in moderate to good yields. The structural identity of each compound was confirmed by common spectroscopic techniques. Aryl quinoline carboxamide derivatives 3.113 – 3.126 were isolated as rotamers, hence, Variable-Temperature Nuclear Magnetic Resonance (VT-NMR) was employed in resolving 1H splitting. At elevated temperature (~328 K); N-methylene carbons were not visible on 13C NMR due to signal line broadening effects. The presence of these nuclei in such cases was, however, supported by 2-dimensional NMR and high-resolution MS data. Most of the compounds achieved in this study displayed promising antimalarial activity against chloroquine-sensitive 3D7 strain of Plasmodium falciparum compared to antitrypanosomal activity against Trypanosoma brucei brucei 427 strain. In particular, compounds 3.80 and 3.108 showed superior activity against chloroquine-sensitive 3D7 P. falciparum strain with IC50 values < 1 μM. More importantly, most of the compounds were non-toxic as determined by HeLa cells, indicating their selectivity towards the parasites. Exploring the space provided on the quinoline scaffold revealed that methoxy incorporation on C-2 is very critical in enhancing antimalarial activity of this class of quinoline compounds. The preliminary SAR of compounds 3.57 – 3.72 showed that compounds containing the 3-cinnamate exhibited enhanced antimalarial activity compared to 2 and 4-cinnamates. Finally, benzamide compounds 3.113 − 3.126 showed poor activity against Mycobacterium tuberculosis H37Rv strain with only compounds 3.113, 3.117 – 3.120 and 3.126 showing appreciable MIC90 values in the range of 40 – 85 μM. , Thesis (MSc) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Authors: Bokosi, Fostino Raphael Bentry
- Date: 2020
- Subjects: Quinoline , Malaria Chemotherapy , Tuberculosis Chemotherapy , African trypanosomiasis Chemotherapy
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/163193 , vital:41017
- Description: The urgent need for new systemic pharmacological entities prompted us to report a library of 2,3-substituted quinoline derivatives. Considering the ubiquity of quinoline-containing compounds in pharmacologically active small molecules, synthesized 2,3-substituted quinoline derivatives were in vitro biologically evaluated for their potential antitubercular, antimalarial and antitrypanosomal activities. Quinoline scaffold was achieved by the Vilsmeier-Haack methodology, affording synthetically useful chloro and formyl substituents on C-2 and C-3 respectively. These two substituents acted as handles in expanding the chemical space around the quinoline ring. Target compounds were synthesized in six to seven steps, employing conventional synthetic organic protocols adapted from various literature. The final compounds were accessed in moderate to good yields. The structural identity of each compound was confirmed by common spectroscopic techniques. Aryl quinoline carboxamide derivatives 3.113 – 3.126 were isolated as rotamers, hence, Variable-Temperature Nuclear Magnetic Resonance (VT-NMR) was employed in resolving 1H splitting. At elevated temperature (~328 K); N-methylene carbons were not visible on 13C NMR due to signal line broadening effects. The presence of these nuclei in such cases was, however, supported by 2-dimensional NMR and high-resolution MS data. Most of the compounds achieved in this study displayed promising antimalarial activity against chloroquine-sensitive 3D7 strain of Plasmodium falciparum compared to antitrypanosomal activity against Trypanosoma brucei brucei 427 strain. In particular, compounds 3.80 and 3.108 showed superior activity against chloroquine-sensitive 3D7 P. falciparum strain with IC50 values < 1 μM. More importantly, most of the compounds were non-toxic as determined by HeLa cells, indicating their selectivity towards the parasites. Exploring the space provided on the quinoline scaffold revealed that methoxy incorporation on C-2 is very critical in enhancing antimalarial activity of this class of quinoline compounds. The preliminary SAR of compounds 3.57 – 3.72 showed that compounds containing the 3-cinnamate exhibited enhanced antimalarial activity compared to 2 and 4-cinnamates. Finally, benzamide compounds 3.113 − 3.126 showed poor activity against Mycobacterium tuberculosis H37Rv strain with only compounds 3.113, 3.117 – 3.120 and 3.126 showing appreciable MIC90 values in the range of 40 – 85 μM. , Thesis (MSc) -- Faculty of Science, Chemistry, 2020
- Full Text:
The novobiocin-induced turnover of fibronectin via low density lipoprotein receptor-related protein 1 alters matrix morphology with physiological consequences on cell growth and migration
- Authors: Boёl, Natasha Marie-Eraine
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/114778 , vital:34034 , 10.21504/10962/114778
- Description: Fibronectin (FN), an extracellular matrix protein, is secreted as a soluble dimer which is assembled into an insoluble extracellular matrix. The dynamics of FN matrix assembly and degradation play a large role in cell migration and invasion thereby contributing to the metastatic potential of cancer cells. Previous studies have shown the direct binding of Heat Shock Protein 90 kDa (Hsp90) and FN in vitro, and that inhibition of Hsp90 with novobiocin (NOV) caused internalisation of the FN matrix. Low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitous receptor known to bind both Hsp90 and FN. Using an LRP1 expressing Hs578T breast cancer cell line and an isogenic mouse embryonic fibroblast (MEF) model system of differential LRP1 expression we demonstrate that LRP1 is involved in turnover of FN in response to C-terminal Hsp90 inhibition. The first objective of this study was to identify the mechanism of NOV-induced LRP1-mediated FN turnover. Our data show that NOV-mediated FN turnover via LRP1 did not require the activity of matrix metalloproteinases (MMPs), which play an important role in processing and degradation of the extracellular matrix and FN. In addition, the levels of the main FN receptor responsible for its extracellular assembly, β1-integrin, did not change in response to NOV. LRP1 is known to undergo regulated intramembrane proteolysis (RIP) which generates smaller fragments that may translocate to the nucleus and modulate gene transcription. Using inhibitors of LRP1 cleavage and nuclear fractionation we determined that LRP1 processing was not required for the NOV-induced FN response suggesting that a mechanism unrelated to LRP1 RIP is involved. A possible mechanism may be in altered Hsp90-LRP1 cell signalling as we observed disruption of the FN-Hsp90-LRP1 complex at the cell surface in NOV treated cells. How this affects downstream eHsp90-LRP1 signalling is still to be determined but may be related to a significant increase in phospho-AKT and loss of phospho-ERK upon NOV-treatment; two key signalling proteins involved in FN matrix regulation and which are downstream of LRP1 signalling. The second objective of this study was to determine the physiological consequences associated with FN turnover in response to NOV treatment. Using migration assays we demonstrated that levels of insoluble matrix-associated FN and FN concentration are not solely responsible for migratory capacity of cells on decellularized extracellular matrices, but rather that structural composition and integrity of the matrix plays a bigger role. Using confocal and scanning electron microscopy, we identified NOV treated matrices to be flatter, less mature and contain thicker, rope-like FN fibrils to which cells adhered better but were generally less proliferative. Comparatively, cells adhered less to the more mature and 3-dimensional untreated matrices but exhibited increased spreading and cell growth, which may in part be due to the thinner fibrils and web-like matrix. In summary, this study substantiates the role of LRP1 in NOV-mediated FN turnover, and provides new insights into the possible mechanisms of the Hsp90-LRP1 mediated loss of FN matrix. This is the first study to demonstrate some of the functional consequences related to FN turnover by NOV at the ECM level. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text: false
- Authors: Boёl, Natasha Marie-Eraine
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/114778 , vital:34034 , 10.21504/10962/114778
- Description: Fibronectin (FN), an extracellular matrix protein, is secreted as a soluble dimer which is assembled into an insoluble extracellular matrix. The dynamics of FN matrix assembly and degradation play a large role in cell migration and invasion thereby contributing to the metastatic potential of cancer cells. Previous studies have shown the direct binding of Heat Shock Protein 90 kDa (Hsp90) and FN in vitro, and that inhibition of Hsp90 with novobiocin (NOV) caused internalisation of the FN matrix. Low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitous receptor known to bind both Hsp90 and FN. Using an LRP1 expressing Hs578T breast cancer cell line and an isogenic mouse embryonic fibroblast (MEF) model system of differential LRP1 expression we demonstrate that LRP1 is involved in turnover of FN in response to C-terminal Hsp90 inhibition. The first objective of this study was to identify the mechanism of NOV-induced LRP1-mediated FN turnover. Our data show that NOV-mediated FN turnover via LRP1 did not require the activity of matrix metalloproteinases (MMPs), which play an important role in processing and degradation of the extracellular matrix and FN. In addition, the levels of the main FN receptor responsible for its extracellular assembly, β1-integrin, did not change in response to NOV. LRP1 is known to undergo regulated intramembrane proteolysis (RIP) which generates smaller fragments that may translocate to the nucleus and modulate gene transcription. Using inhibitors of LRP1 cleavage and nuclear fractionation we determined that LRP1 processing was not required for the NOV-induced FN response suggesting that a mechanism unrelated to LRP1 RIP is involved. A possible mechanism may be in altered Hsp90-LRP1 cell signalling as we observed disruption of the FN-Hsp90-LRP1 complex at the cell surface in NOV treated cells. How this affects downstream eHsp90-LRP1 signalling is still to be determined but may be related to a significant increase in phospho-AKT and loss of phospho-ERK upon NOV-treatment; two key signalling proteins involved in FN matrix regulation and which are downstream of LRP1 signalling. The second objective of this study was to determine the physiological consequences associated with FN turnover in response to NOV treatment. Using migration assays we demonstrated that levels of insoluble matrix-associated FN and FN concentration are not solely responsible for migratory capacity of cells on decellularized extracellular matrices, but rather that structural composition and integrity of the matrix plays a bigger role. Using confocal and scanning electron microscopy, we identified NOV treated matrices to be flatter, less mature and contain thicker, rope-like FN fibrils to which cells adhered better but were generally less proliferative. Comparatively, cells adhered less to the more mature and 3-dimensional untreated matrices but exhibited increased spreading and cell growth, which may in part be due to the thinner fibrils and web-like matrix. In summary, this study substantiates the role of LRP1 in NOV-mediated FN turnover, and provides new insights into the possible mechanisms of the Hsp90-LRP1 mediated loss of FN matrix. This is the first study to demonstrate some of the functional consequences related to FN turnover by NOV at the ECM level. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text: false
Understanding the livelihoods of Zimbabwean informal traders in South Africa: the case of Makhanda
- Musiyandaka, Tariro Henrietta
- Authors: Musiyandaka, Tariro Henrietta
- Date: 2020
- Subjects: Informal sector (Economics) South Africa Makhanda , Foreign workers, Zimbabwean South Africa Makhanda Economic conditions , Foreign workers, Zimbabwean South Africa Makhanda Social conditions , Street vendors South Africa Makhanda
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/164535 , vital:41127
- Description: Increasingly, Zimbabweans are migrating from their country for both economic and political reasons, with South Africa being the primary destination. In seeking employment in South Africa, Zimbabweans face numerous initial problems, including the high unemployment rate in the country alongside restrictions on their employment in the formal economy. In this context, Zimbabweans often turn to work in the informal economy, including as informal traders. This thesis seeks to understand the lives and livelihoods of Zimbabwean informal traders in Makhanda in the Eastern Cape Province of South Africa. Drawing upon the Sustainable Livelihoods Approach, and in the light of existing literature on Zimbabweans more broadly in South Africa, the thesis examines the livelihoods of a purposeful sampled grouping of six informal traders from Zimbabwe in Makhanda. It discusses their reasons for leaving Zimbabwe, their journey from Zimbabwe to Makhanda, relationships amongst themselves and their ongoing relationships with family back home, as well as their hopes and plans for the future. It also examines more specifically their livelihood activities, the daily challenges they face in pursuing their livelihoods and concerns about their livelihood status in South Africa. Despite the many deep-rooted systemic obstacles confronting these Zimbabwean informal traders, the thesis concludes that they demonstrate significant micro-level ingenuity in pursuing their livelihoods in South Africa. , Thesis (MA) -- Faculty of Faculty of Humanities, Sociology, 2020
- Full Text:
- Authors: Musiyandaka, Tariro Henrietta
- Date: 2020
- Subjects: Informal sector (Economics) South Africa Makhanda , Foreign workers, Zimbabwean South Africa Makhanda Economic conditions , Foreign workers, Zimbabwean South Africa Makhanda Social conditions , Street vendors South Africa Makhanda
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/164535 , vital:41127
- Description: Increasingly, Zimbabweans are migrating from their country for both economic and political reasons, with South Africa being the primary destination. In seeking employment in South Africa, Zimbabweans face numerous initial problems, including the high unemployment rate in the country alongside restrictions on their employment in the formal economy. In this context, Zimbabweans often turn to work in the informal economy, including as informal traders. This thesis seeks to understand the lives and livelihoods of Zimbabwean informal traders in Makhanda in the Eastern Cape Province of South Africa. Drawing upon the Sustainable Livelihoods Approach, and in the light of existing literature on Zimbabweans more broadly in South Africa, the thesis examines the livelihoods of a purposeful sampled grouping of six informal traders from Zimbabwe in Makhanda. It discusses their reasons for leaving Zimbabwe, their journey from Zimbabwe to Makhanda, relationships amongst themselves and their ongoing relationships with family back home, as well as their hopes and plans for the future. It also examines more specifically their livelihood activities, the daily challenges they face in pursuing their livelihoods and concerns about their livelihood status in South Africa. Despite the many deep-rooted systemic obstacles confronting these Zimbabwean informal traders, the thesis concludes that they demonstrate significant micro-level ingenuity in pursuing their livelihoods in South Africa. , Thesis (MA) -- Faculty of Faculty of Humanities, Sociology, 2020
- Full Text:
A medicinal chemistry study in nitrogen containing heterocycles
- Authors: Lunga, Mayibongwe Junior
- Date: 2018
- Subjects: Indole , Tetrazoles , Antimalarials , Heat shock proteins , Plasmodium falciparum
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/63521 , vital:28430
- Description: Heterocyclic structures have found extensive utility in the field of medicinal chemistry, as prominent regions of pharmacophores resulting in numerous drug treatments for many diseases. Accordingly, in this project we explored the respective antimalarial and anticancer activity exhibited by compounds featuring nitrogen containing indole and tetrazole heterocycles respectively. This thesis therefore comprises of two distinct parts. Part 1. Following the development of resistance towards traditional antimalarial therapy such as chloroquine and emerging resistance towards artemisinin combination therapies, the WHO reported the urgent need for new, effective drugs and identification of new drug targets to combat the Plasmodium falciparum parasite. In 2015 the parasite was the cause of 429 000 deaths, the majority occurring in the sub-Saharan region of Africa. This highlights the failing effectiveness of vector control strategies, reiterating the need to develop alternative control and treatment strategies. In response to this need we wanted to expand and further describe the SAR of the indole based series, indolyl-3-ethanone-α- thioethers, previously synthesized in our laboratory. These compounds were found to exhibit antimalarial activity with compounds 2.26 and 2.27 exhibiting activity against P. falciparum 3D7 in the nanomolar range. Based on these compounds we synthesized compounds 3.21 and 3.24 – 3.32 following a three step reaction pathway. Our results in this study, indicate that compound 3.28, a pnitrothiophenol analogue of 2.27 was the most active of the compounds we synthesized and furthermore was superior in activity against Plasmodium compared to 2.27. This result indicated that the presence of p-NO2 is important in enhancing anti-plasmodial activity. Comparing compounds 3.25 and 3.26 with an oxygen on the ether bridge to compounds 3.29 and 3.30 with a sulfur, we observed an increase in hydrophilicity coupled to a decrease in anti-plasmodial activity in the compounds, thus, highlighting the importance of sulfur for enhanced activity. Furthermore, we investigated bioisosteric replacement of the 5-chloro substituent present in hit compounds 2.27 and 3.28, with an electron withdrawing nitrile (3.27) and electron donating methyl (3.29) and methoxy (3.31) substituents. These substituents decreased anti-plasmodial activity, confirming that a chlorine substituent is optimal for biological activity. This study furthered our understanding of the SAR of indolyl-3-ethanone-α- thioethers for the development of potent anti-plasmodial lead compounds. Part 2. Triple negative breast cancer (TNBC), which disproportionately affects women of sub-Saharan Africa, is unresponsive to hormone-based therapies. This emergence presents a population of patients devoid of effective drug treatment, signaling the urgent need to develop new effective therapies with novel drug targets. Therefore, we identified our target in TNBC cells as the protein-protein interaction between the co-chaperones HOP and HSP90. We reasoned that a disruption of this interaction would ultimately result in cancer cell death via the degradation of essential oncogenic client proteins. Following a fragment screening campaign, which identified several acid and tetrazole containing hits (4.56 – 4.58) which bound to HOP, with low anticancer activity, we sought to develop synthetic methodology to elaborate our fragment hits synthesizing tetrazole containing fragments to target TNBC cell lines. We therefore proceeded to synthesize a range of multi substituted fragments (4.59 – 4.63), utilizing a nitrile (4.66) to access tetrazoles via 1,3-cycloaddition and an acid by nitrile hydrolysis. We successfully synthesized the tetrazole and acid fragments which are currently undergoing characterization for activity against TNBC. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
- Full Text:
- Authors: Lunga, Mayibongwe Junior
- Date: 2018
- Subjects: Indole , Tetrazoles , Antimalarials , Heat shock proteins , Plasmodium falciparum
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/63521 , vital:28430
- Description: Heterocyclic structures have found extensive utility in the field of medicinal chemistry, as prominent regions of pharmacophores resulting in numerous drug treatments for many diseases. Accordingly, in this project we explored the respective antimalarial and anticancer activity exhibited by compounds featuring nitrogen containing indole and tetrazole heterocycles respectively. This thesis therefore comprises of two distinct parts. Part 1. Following the development of resistance towards traditional antimalarial therapy such as chloroquine and emerging resistance towards artemisinin combination therapies, the WHO reported the urgent need for new, effective drugs and identification of new drug targets to combat the Plasmodium falciparum parasite. In 2015 the parasite was the cause of 429 000 deaths, the majority occurring in the sub-Saharan region of Africa. This highlights the failing effectiveness of vector control strategies, reiterating the need to develop alternative control and treatment strategies. In response to this need we wanted to expand and further describe the SAR of the indole based series, indolyl-3-ethanone-α- thioethers, previously synthesized in our laboratory. These compounds were found to exhibit antimalarial activity with compounds 2.26 and 2.27 exhibiting activity against P. falciparum 3D7 in the nanomolar range. Based on these compounds we synthesized compounds 3.21 and 3.24 – 3.32 following a three step reaction pathway. Our results in this study, indicate that compound 3.28, a pnitrothiophenol analogue of 2.27 was the most active of the compounds we synthesized and furthermore was superior in activity against Plasmodium compared to 2.27. This result indicated that the presence of p-NO2 is important in enhancing anti-plasmodial activity. Comparing compounds 3.25 and 3.26 with an oxygen on the ether bridge to compounds 3.29 and 3.30 with a sulfur, we observed an increase in hydrophilicity coupled to a decrease in anti-plasmodial activity in the compounds, thus, highlighting the importance of sulfur for enhanced activity. Furthermore, we investigated bioisosteric replacement of the 5-chloro substituent present in hit compounds 2.27 and 3.28, with an electron withdrawing nitrile (3.27) and electron donating methyl (3.29) and methoxy (3.31) substituents. These substituents decreased anti-plasmodial activity, confirming that a chlorine substituent is optimal for biological activity. This study furthered our understanding of the SAR of indolyl-3-ethanone-α- thioethers for the development of potent anti-plasmodial lead compounds. Part 2. Triple negative breast cancer (TNBC), which disproportionately affects women of sub-Saharan Africa, is unresponsive to hormone-based therapies. This emergence presents a population of patients devoid of effective drug treatment, signaling the urgent need to develop new effective therapies with novel drug targets. Therefore, we identified our target in TNBC cells as the protein-protein interaction between the co-chaperones HOP and HSP90. We reasoned that a disruption of this interaction would ultimately result in cancer cell death via the degradation of essential oncogenic client proteins. Following a fragment screening campaign, which identified several acid and tetrazole containing hits (4.56 – 4.58) which bound to HOP, with low anticancer activity, we sought to develop synthetic methodology to elaborate our fragment hits synthesizing tetrazole containing fragments to target TNBC cell lines. We therefore proceeded to synthesize a range of multi substituted fragments (4.59 – 4.63), utilizing a nitrile (4.66) to access tetrazoles via 1,3-cycloaddition and an acid by nitrile hydrolysis. We successfully synthesized the tetrazole and acid fragments which are currently undergoing characterization for activity against TNBC. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
- Full Text:
Aligning local government service delivery communication with digital citizen engagement: a case study of Makana Municipality
- Authors: Machiri, Mwazvita Chipo
- Date: 2018
- Subjects: Political participation South Africa Makana , Municipal services South Africa Makana , Communication in public administration South Africa Makana , Internet in public administration South Africa Makana , Information technology South Africa Makana , Electronic government information South Africa Makana , Government accountability South Africa Makana
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/194146 , vital:45423
- Description: The effective management of local municipalities in South Africa determines the quality of service delivery to citizens. Policies and other legislation have been implemented in an attempt to improve service delivery backlogs in South Africa since post-apartheid. However, these have not been effective in meeting community needs, hence leading to poor service delivery and increased community protests of frustration. These problems are partly linked to the lack of communication between government and citizens, and within internal government. Government needs to be held accountable for the services it provides, and improve on these services through practicing transparency, providing information to citizens, and allowing citizens to provide feedback on the various challenges experienced. Information access and communication is vital to the citizen engagement process, as this supports evidence-based engagement between citizens and government. Over the most recent years, innovative ICTs have emerged as a critical strategic tool in facilitating communication between the government and its citizens, commonly referred to as digital citizen engagement. The effective implementation of such initiatives at the local government level, especially in resource-constrained contexts, is not straightforward. This research aims to develop a guiding framework for aligning municipal communication processes with innovative ICTs to support ongoing social accountability and transparency through citizen engagement in local municipalities. The formulation of this framework is built on the Adaptive Structuration Theory, which is based on studying organisational change that occurs due to implementation and adoption of technology. Using a pragmatist approach and case study of Makana Municipality, the research study investigates a digital citizen engagement initiative called MobiSAM (Mobile Social Accountability Monitoring). The key findings from the qualitative empirical investigation indicates that there are significant social and political factors to consider when aligning Digital Citizen Engagement initiatives in a resource-constrained environment. The findings illustrated that the change and alignment process of DCE in local municipalities rely on a diverse set of inputs from different stakeholders, and a dynamic change process, which result in key citizen engagement outcomes of empowerment, accountability, transparency, and increased engagement depending – all depending on the success of the process. The extent of the outcomes will vary with the effectiveness of change management, idea generation, and participation, which Preliminaries are impacted by perceived usefulness, attitude towards the system, and the intentions of the user. The proposed framework provides a guideline for the implementation and introduction of innovations ICTs for citizen engagement at local government level. , Thesis (MCom) -- Faculty of Commerce, Information Systems, 2018
- Full Text:
- Authors: Machiri, Mwazvita Chipo
- Date: 2018
- Subjects: Political participation South Africa Makana , Municipal services South Africa Makana , Communication in public administration South Africa Makana , Internet in public administration South Africa Makana , Information technology South Africa Makana , Electronic government information South Africa Makana , Government accountability South Africa Makana
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/194146 , vital:45423
- Description: The effective management of local municipalities in South Africa determines the quality of service delivery to citizens. Policies and other legislation have been implemented in an attempt to improve service delivery backlogs in South Africa since post-apartheid. However, these have not been effective in meeting community needs, hence leading to poor service delivery and increased community protests of frustration. These problems are partly linked to the lack of communication between government and citizens, and within internal government. Government needs to be held accountable for the services it provides, and improve on these services through practicing transparency, providing information to citizens, and allowing citizens to provide feedback on the various challenges experienced. Information access and communication is vital to the citizen engagement process, as this supports evidence-based engagement between citizens and government. Over the most recent years, innovative ICTs have emerged as a critical strategic tool in facilitating communication between the government and its citizens, commonly referred to as digital citizen engagement. The effective implementation of such initiatives at the local government level, especially in resource-constrained contexts, is not straightforward. This research aims to develop a guiding framework for aligning municipal communication processes with innovative ICTs to support ongoing social accountability and transparency through citizen engagement in local municipalities. The formulation of this framework is built on the Adaptive Structuration Theory, which is based on studying organisational change that occurs due to implementation and adoption of technology. Using a pragmatist approach and case study of Makana Municipality, the research study investigates a digital citizen engagement initiative called MobiSAM (Mobile Social Accountability Monitoring). The key findings from the qualitative empirical investigation indicates that there are significant social and political factors to consider when aligning Digital Citizen Engagement initiatives in a resource-constrained environment. The findings illustrated that the change and alignment process of DCE in local municipalities rely on a diverse set of inputs from different stakeholders, and a dynamic change process, which result in key citizen engagement outcomes of empowerment, accountability, transparency, and increased engagement depending – all depending on the success of the process. The extent of the outcomes will vary with the effectiveness of change management, idea generation, and participation, which Preliminaries are impacted by perceived usefulness, attitude towards the system, and the intentions of the user. The proposed framework provides a guideline for the implementation and introduction of innovations ICTs for citizen engagement at local government level. , Thesis (MCom) -- Faculty of Commerce, Information Systems, 2018
- Full Text:
An investigation into the bacterial communities associated with pyrroloiminoquinone-producing South African latrunculid sponges
- Authors: Hilliar, Storm Hannah
- Date: 2018
- Subjects: Sponges South Africa Algoa Bay , Betaproteobacteria , Spirochaeta , Symbiosis , Bacterial communities
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/62112 , vital:28128
- Description: Marine sponges belonging to the family Latrunculiidae are known for their production of cytotoxic pyrroloiminoquinone alkaloids and the South African coast provides a unique environment for the exploitation of these potent bioactive compounds. The isolation of structurally similar pyrroloiminoquinone compounds from unrelated, non poriferan sources has led to the suggestion that South African latrunculid pyrroloiminoquinones may be secondary metabolites produced by sponge associated microbial symbionts. Previous studies investigating the bacterial communities of South African latrunculid sponges have shown the conservation of distinct microbial populations with unusual bacterial taxa dominated by a novel betaproteobacterial and spirochete species. This study describes the further investigation into these associated bacterial communities, their conservation and sponge microbiome comparisons across spatial, temporal and environmental scales. The bacterial communities associated with seven latrunculid species representing three genera (Tsitsikamma, Cyclacanthia and Latrunculia) were characterized as well as a Mycale and Tethya rubra species. Latrunculid sponge microbiomes were significantly different from those associated with sympatric outlier sponge species and the surrounding environment. The bacterial communities associated with latrunculid sponges appear host specific with the conservation of two dominant bacterial symbionts which mirror the phylogeny of their host species. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2018
- Full Text:
- Authors: Hilliar, Storm Hannah
- Date: 2018
- Subjects: Sponges South Africa Algoa Bay , Betaproteobacteria , Spirochaeta , Symbiosis , Bacterial communities
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/62112 , vital:28128
- Description: Marine sponges belonging to the family Latrunculiidae are known for their production of cytotoxic pyrroloiminoquinone alkaloids and the South African coast provides a unique environment for the exploitation of these potent bioactive compounds. The isolation of structurally similar pyrroloiminoquinone compounds from unrelated, non poriferan sources has led to the suggestion that South African latrunculid pyrroloiminoquinones may be secondary metabolites produced by sponge associated microbial symbionts. Previous studies investigating the bacterial communities of South African latrunculid sponges have shown the conservation of distinct microbial populations with unusual bacterial taxa dominated by a novel betaproteobacterial and spirochete species. This study describes the further investigation into these associated bacterial communities, their conservation and sponge microbiome comparisons across spatial, temporal and environmental scales. The bacterial communities associated with seven latrunculid species representing three genera (Tsitsikamma, Cyclacanthia and Latrunculia) were characterized as well as a Mycale and Tethya rubra species. Latrunculid sponge microbiomes were significantly different from those associated with sympatric outlier sponge species and the surrounding environment. The bacterial communities associated with latrunculid sponges appear host specific with the conservation of two dominant bacterial symbionts which mirror the phylogeny of their host species. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2018
- Full Text:
Chipangano: vigilantism and community responses in Mbare District, Zimbabwe, c.2000-2013
- Authors: Munyarari, Tinashe
- Date: 2018
- Subjects: Vigilantism Zimbabwe Mbare , ZANU-PF (Organization : Zimbabwe) , Zimbabwe History 1980- , Vigilantism Zimbabwe Mbare Public opinion , Collective memory Zimbabwe Mbare
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/62126 , vital:28130
- Description: This study examines an aspect of Zimbabwe’s political history, namely the emergence and operations of Chipangano vigilante group in Mbare (2000-2013) and how the community responded to the scourges of this vigilante group. This study shows that Chipangano, which means a pact, was formed with the intention to extend ZANU-PF patronage system, canvassing support and regain control of Mbare district from the MDC. The group consolidated itself as a shadow militia group for ZANU-PF that intimidated the opposition parties and coerced the general populace to attend ZANU-PF functions. It also shows that the vigilante group seized Harare City Council’s duties, such as collecting gate-takings from local and long distance public transport at Mbare Bus Terminal; controlling allocations of market stalls and collecting rents from market stalls, for personal benefits. The group also politicised the access to local state property. Chipangano’s collusion with ZANU-PF and state structures licensed it to engage in criminal activities with impunity, thus this thesis seeks to understand the relationship between the vigilantes, ZANU-PF and state structures. The activities of Chipangano such as abduction, intimidation, beatings, killings and displacement of people resulted in social trauma. This thesis will also explore how this phase of violence is remembered today by the research informants. , Thesis (MA) -- Faculty of Humanities, History, 2018
- Full Text:
- Authors: Munyarari, Tinashe
- Date: 2018
- Subjects: Vigilantism Zimbabwe Mbare , ZANU-PF (Organization : Zimbabwe) , Zimbabwe History 1980- , Vigilantism Zimbabwe Mbare Public opinion , Collective memory Zimbabwe Mbare
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/62126 , vital:28130
- Description: This study examines an aspect of Zimbabwe’s political history, namely the emergence and operations of Chipangano vigilante group in Mbare (2000-2013) and how the community responded to the scourges of this vigilante group. This study shows that Chipangano, which means a pact, was formed with the intention to extend ZANU-PF patronage system, canvassing support and regain control of Mbare district from the MDC. The group consolidated itself as a shadow militia group for ZANU-PF that intimidated the opposition parties and coerced the general populace to attend ZANU-PF functions. It also shows that the vigilante group seized Harare City Council’s duties, such as collecting gate-takings from local and long distance public transport at Mbare Bus Terminal; controlling allocations of market stalls and collecting rents from market stalls, for personal benefits. The group also politicised the access to local state property. Chipangano’s collusion with ZANU-PF and state structures licensed it to engage in criminal activities with impunity, thus this thesis seeks to understand the relationship between the vigilantes, ZANU-PF and state structures. The activities of Chipangano such as abduction, intimidation, beatings, killings and displacement of people resulted in social trauma. This thesis will also explore how this phase of violence is remembered today by the research informants. , Thesis (MA) -- Faculty of Humanities, History, 2018
- Full Text:
Evaluating metabolism-induced toxicity using a non-hepatic cell line
- Authors: Weyers, Carli
- Date: 2018
- Subjects: Cytochrome P-450 , Drugs Metabolism , Drugs Design
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/61950 , vital:28087
- Description: The drug discovery pipeline is a complicated process taking roughly 15 years to complete, costing in excess of $1 billion per new chemical entity. It has been estimated that for every 100, 000 promising hit or lead compounds, only one will make it onto the market due to numerous drug candidates being discarded because of many complications. One such complication is metabolism-induced toxicity. Accordingly, an early understanding of the metabolism of any new chemical entity is becoming an integral part of the pipeline. In order to explore this, various methods have been developed including in silico and in vitro techniques. One such method involves performing cell viability assays on human liver cancer cell lines, which overexpress specific metabolic cytochrome P450 enzymes. If a toxic metabolite is produced it would result in reduced cell viability of the transformed cell line in comparison to a control. Since the liver is the primary site of metabolism in the human body, we were curious as to the extent to which background metabolism may play a role in the degree to which toxic metabolites would be produced in these cell lines. The aim of this project, therefore, was to establish if a non-hepatic cell-based system which overexpresses CYP3A4 could be used to detect the metabolism and any subsequent toxicity of compounds which have been reported to be substrates of the CYP450 enzyme. The HEK293 cell line was stably transfected with a plasmid vector for human CYP3A4 to create a model overexpression system for our metabolism studies. The activity of the enzyme was confirmed using the substrate, 7-benzyloxy-4-trifluoromethyl-coumarin. Subsequently, cytotoxicity testing was done on four known pharmaceuticals reported to generate toxic metabolites in hepatic cell-based assays. In silico metabolic predictions on the four known compounds were performed and compared to the results of published literature. Finally, the metabolism of one compound was studied using a combination of high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) in order to detect predicted metabolites. We observed no change in cellular toxicity nor did we detect the formation of metabolites, even though the overexpressed CYP3A4 enzyme was active. The results suggest that caution should be taken when interpreting the results of cell-based metabolism studies, and background metabolism may play a significant role in the data. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
- Full Text:
- Authors: Weyers, Carli
- Date: 2018
- Subjects: Cytochrome P-450 , Drugs Metabolism , Drugs Design
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/61950 , vital:28087
- Description: The drug discovery pipeline is a complicated process taking roughly 15 years to complete, costing in excess of $1 billion per new chemical entity. It has been estimated that for every 100, 000 promising hit or lead compounds, only one will make it onto the market due to numerous drug candidates being discarded because of many complications. One such complication is metabolism-induced toxicity. Accordingly, an early understanding of the metabolism of any new chemical entity is becoming an integral part of the pipeline. In order to explore this, various methods have been developed including in silico and in vitro techniques. One such method involves performing cell viability assays on human liver cancer cell lines, which overexpress specific metabolic cytochrome P450 enzymes. If a toxic metabolite is produced it would result in reduced cell viability of the transformed cell line in comparison to a control. Since the liver is the primary site of metabolism in the human body, we were curious as to the extent to which background metabolism may play a role in the degree to which toxic metabolites would be produced in these cell lines. The aim of this project, therefore, was to establish if a non-hepatic cell-based system which overexpresses CYP3A4 could be used to detect the metabolism and any subsequent toxicity of compounds which have been reported to be substrates of the CYP450 enzyme. The HEK293 cell line was stably transfected with a plasmid vector for human CYP3A4 to create a model overexpression system for our metabolism studies. The activity of the enzyme was confirmed using the substrate, 7-benzyloxy-4-trifluoromethyl-coumarin. Subsequently, cytotoxicity testing was done on four known pharmaceuticals reported to generate toxic metabolites in hepatic cell-based assays. In silico metabolic predictions on the four known compounds were performed and compared to the results of published literature. Finally, the metabolism of one compound was studied using a combination of high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) in order to detect predicted metabolites. We observed no change in cellular toxicity nor did we detect the formation of metabolites, even though the overexpressed CYP3A4 enzyme was active. The results suggest that caution should be taken when interpreting the results of cell-based metabolism studies, and background metabolism may play a significant role in the data. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
- Full Text:
Exploring para-thiophenols to expand the SAR of antimalarial 3-indolylethanones
- Authors: Chisango, Ruramai Lissa
- Date: 2018
- Subjects: Antimalarials , Malaria Chemotherapy , Thiols , Plasmodium falciparum , Blood-brain barrier
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/63515 , vital:28428
- Description: According to the WHO, malaria is responsible for over half a million deaths annually especially in populations from disadvantaged settings. Although there has been a documented improvement in the mortality rates, malaria has proved to be a global emergency. Mostly affecting the poor population, this disease is perpetuating a vicious cycle of poverty in the developing world as current preventive measures are not adequate unless adopted in addition to effective treatment. However, there has been a worldwide increase in resistance to available treatment which presents a need for novel, affordable treatment. A study conducted in our laboratory identified two hit thiophenol containing compounds 2.24 and 2.25. These molecules provided initial insight into the SAR and potential pharmacophore of this class of compounds. We decided to further explore these compounds by making bioisosteric replacements to optimize the structure as we monitor the effect of these modifications on the anti-plasmodial activity. The synthetic pathway to form the target compounds of our study comprised of three steps which were initiated by the Friedel-Crafts acetylation of the indoles resulting in compounds 3.5 - 3.7. A bromination step followed which yielded the -bromo ketones (3.8 - 3.11). Some of the thiophenols (3.14 and 3.16) were not readily available in our laboratory and so were synthesized for the final synthetic step. This step involved the nucleophilic displacement of the -bromine to generate the -aryl substituted 3-indolylethanones (3.17 - 3.27). The thioethers displayed improved antimalarial activity from 2.24 and 2.25 against the chloroquine sensitive 3D7 Plasmodium falciparum strain. In addition, these compounds were non-toxic against HeLa cells which indicated this potential novel class of antimalarials is selective for the malaria parasite as hypothesized in the previous study conducted in our laboratory. In an attempt to predict the bioavailability of some of our compounds, in silico studies were conducted revealing that these compounds could be passively absorbed by the gastrointestinal tract, a positive result for bioavailability purposes. However, results from these studies indicate that modifications of these compounds would be necessary to allow for permeation through the blood brain barrier (BBB) for instances when the patient has cerebral malaria. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
- Full Text:
- Authors: Chisango, Ruramai Lissa
- Date: 2018
- Subjects: Antimalarials , Malaria Chemotherapy , Thiols , Plasmodium falciparum , Blood-brain barrier
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/63515 , vital:28428
- Description: According to the WHO, malaria is responsible for over half a million deaths annually especially in populations from disadvantaged settings. Although there has been a documented improvement in the mortality rates, malaria has proved to be a global emergency. Mostly affecting the poor population, this disease is perpetuating a vicious cycle of poverty in the developing world as current preventive measures are not adequate unless adopted in addition to effective treatment. However, there has been a worldwide increase in resistance to available treatment which presents a need for novel, affordable treatment. A study conducted in our laboratory identified two hit thiophenol containing compounds 2.24 and 2.25. These molecules provided initial insight into the SAR and potential pharmacophore of this class of compounds. We decided to further explore these compounds by making bioisosteric replacements to optimize the structure as we monitor the effect of these modifications on the anti-plasmodial activity. The synthetic pathway to form the target compounds of our study comprised of three steps which were initiated by the Friedel-Crafts acetylation of the indoles resulting in compounds 3.5 - 3.7. A bromination step followed which yielded the -bromo ketones (3.8 - 3.11). Some of the thiophenols (3.14 and 3.16) were not readily available in our laboratory and so were synthesized for the final synthetic step. This step involved the nucleophilic displacement of the -bromine to generate the -aryl substituted 3-indolylethanones (3.17 - 3.27). The thioethers displayed improved antimalarial activity from 2.24 and 2.25 against the chloroquine sensitive 3D7 Plasmodium falciparum strain. In addition, these compounds were non-toxic against HeLa cells which indicated this potential novel class of antimalarials is selective for the malaria parasite as hypothesized in the previous study conducted in our laboratory. In an attempt to predict the bioavailability of some of our compounds, in silico studies were conducted revealing that these compounds could be passively absorbed by the gastrointestinal tract, a positive result for bioavailability purposes. However, results from these studies indicate that modifications of these compounds would be necessary to allow for permeation through the blood brain barrier (BBB) for instances when the patient has cerebral malaria. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2018
- Full Text:
Production, purification, and characterisation of proteases from an ericoid mycorrhizal fungus, Oidiodendron maius
- Authors: Manyumwa, Colleen Varaidzo
- Date: 2018
- Subjects: Ascomycetes , Mycorrhizal fungi , Ericaceae , Proteolytic enzymes , Silver Recycling
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/62833 , vital:28298
- Description: The aim of this study was to produce, purify and characterise proteases from the ericoid mycorrhizal fungus, Oidiodendron maius (CafRU082b/KP119480), as well as to explore their potential application in the recovery of silver from X-ray film. Firstly, the growth of the ericoid mycorrhizal fungus, Oidiodendron maius (CafRU082b), was studied, and its ability to produce proteolytic enzymes was investigated. O. maius proved to grow well in the dark, submerged in Modified Melin Norkran’s liquid medium at a pH of 5 and at 25°C. Pure cultures of the fungus were maintained on Potato Dextrose Agar (PDA). The fungus grew on PDA plates containing different substrates including haemoglobin, casein, gelatin as well as azocasein. Zones of clearance, however, were only observed on plates containing gelatin after treatment with mercuric chloride, HgCl2. Proteases were successfully produced after 14 days when gelatin was incorporated into the growth medium. After production of the proteases, purification and characterisation of the enzymes was performed. Purification of the enzymes was performed by acetone precipitation followed by ultrafiltration with 50 kDa and 30 kDa cut off membrane filters. A final purification fold of approximately 37.6 was achieved. Unusual yields of above 100% were observed after each purification step with the final yield achieved being 196% with a final specific activity of 2707 U/mg. SDS-PAGE revealed a protease band of 35 kDa which was also visible on the zymogram at approximately 36 kDa. The zymogram showed clear hydrolysis bands against a blue background after staining with Coomassie Brilliant Blue. Physico-chemical characterisation of the protease revealed its pH optimum to be pH 3.0 and its temperature optimum 68°C. Another peak was observed on the pH profile at pH 7.0. The protease exhibited high thermostability at temperatures 37°C, 80°C as well as 100°C with the enzyme retaining close to 50% of its initial activity after 4 h of exposure to all three temperatures. All ions tested for their effects on the proteases, except Ca2+, enhanced protease activity. Ca2+ did not exhibit any significant effect on the enzyme’s activity while Zn2+ had the highest effect, enhancing enzyme activity by 305%. The proteases, however, were not significantly inhibited by EDTA, a metal chelating agent and a known metalloprotease inhibitor. The enzyme was classified as an aspartic protease due to complete inhibition by 25 μM of pepstatin A, coupled to its low pH optimum of 3.0. Addition of trans-Epoxysuccinyl-L-leucylamido-(4-guanidino)butane (E-64), a cysteine protease inhibitor, and 2-mercaptoethanol increased protease activity. The proteases exhibited a narrow substrate specificity towards gelatin and no other substrate. Substrate kinetics values were plotted on a Michaelis-Menten Graph and showed that the enzyme had a Vmax of 55.25 U/ml and a Km of 2.7 mg/ml gelatin. A low Km indicated that the protease had a high affinity for gelatin. Silver recovery studies from X-ray film revealed the proteases’ capability to remove silver from X-ray film, leaving the film intact. The recovery of silver was perceived visually, by film observation, as well as by scan electron microscopy (SEM) images, where clearance of the film was observed after incubation with the enzyme. Energy dispersive X-ray spectroscopy (EDS) profiles also confirmed removal of silver from the film, with a Ag peak showing on the profile of the film before treatment with the proteases and no peak after treatment. The crude protease sample was, however, catalytically more efficient compared to the partially purified sample. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2018
- Full Text:
- Authors: Manyumwa, Colleen Varaidzo
- Date: 2018
- Subjects: Ascomycetes , Mycorrhizal fungi , Ericaceae , Proteolytic enzymes , Silver Recycling
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/62833 , vital:28298
- Description: The aim of this study was to produce, purify and characterise proteases from the ericoid mycorrhizal fungus, Oidiodendron maius (CafRU082b/KP119480), as well as to explore their potential application in the recovery of silver from X-ray film. Firstly, the growth of the ericoid mycorrhizal fungus, Oidiodendron maius (CafRU082b), was studied, and its ability to produce proteolytic enzymes was investigated. O. maius proved to grow well in the dark, submerged in Modified Melin Norkran’s liquid medium at a pH of 5 and at 25°C. Pure cultures of the fungus were maintained on Potato Dextrose Agar (PDA). The fungus grew on PDA plates containing different substrates including haemoglobin, casein, gelatin as well as azocasein. Zones of clearance, however, were only observed on plates containing gelatin after treatment with mercuric chloride, HgCl2. Proteases were successfully produced after 14 days when gelatin was incorporated into the growth medium. After production of the proteases, purification and characterisation of the enzymes was performed. Purification of the enzymes was performed by acetone precipitation followed by ultrafiltration with 50 kDa and 30 kDa cut off membrane filters. A final purification fold of approximately 37.6 was achieved. Unusual yields of above 100% were observed after each purification step with the final yield achieved being 196% with a final specific activity of 2707 U/mg. SDS-PAGE revealed a protease band of 35 kDa which was also visible on the zymogram at approximately 36 kDa. The zymogram showed clear hydrolysis bands against a blue background after staining with Coomassie Brilliant Blue. Physico-chemical characterisation of the protease revealed its pH optimum to be pH 3.0 and its temperature optimum 68°C. Another peak was observed on the pH profile at pH 7.0. The protease exhibited high thermostability at temperatures 37°C, 80°C as well as 100°C with the enzyme retaining close to 50% of its initial activity after 4 h of exposure to all three temperatures. All ions tested for their effects on the proteases, except Ca2+, enhanced protease activity. Ca2+ did not exhibit any significant effect on the enzyme’s activity while Zn2+ had the highest effect, enhancing enzyme activity by 305%. The proteases, however, were not significantly inhibited by EDTA, a metal chelating agent and a known metalloprotease inhibitor. The enzyme was classified as an aspartic protease due to complete inhibition by 25 μM of pepstatin A, coupled to its low pH optimum of 3.0. Addition of trans-Epoxysuccinyl-L-leucylamido-(4-guanidino)butane (E-64), a cysteine protease inhibitor, and 2-mercaptoethanol increased protease activity. The proteases exhibited a narrow substrate specificity towards gelatin and no other substrate. Substrate kinetics values were plotted on a Michaelis-Menten Graph and showed that the enzyme had a Vmax of 55.25 U/ml and a Km of 2.7 mg/ml gelatin. A low Km indicated that the protease had a high affinity for gelatin. Silver recovery studies from X-ray film revealed the proteases’ capability to remove silver from X-ray film, leaving the film intact. The recovery of silver was perceived visually, by film observation, as well as by scan electron microscopy (SEM) images, where clearance of the film was observed after incubation with the enzyme. Energy dispersive X-ray spectroscopy (EDS) profiles also confirmed removal of silver from the film, with a Ag peak showing on the profile of the film before treatment with the proteases and no peak after treatment. The crude protease sample was, however, catalytically more efficient compared to the partially purified sample. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2018
- Full Text:
Vachellia erioloba (camel thorn) and microbial interactions
- Authors: Van Aswegen, Sunet
- Date: 2018
- Subjects: Vesicular-arbuscular mycorrhizas , Cadmium , Rhizobacteria , Plant growth-promoting rhizobacteria , Acacia erioloba
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/63716 , vital:28475
- Description: Vachellia erioloba (camel thorn) is one of South Africa’s economically important tree species and therefore requires further investigation to improve its health and growth. Beneficial soil microbes have positive effects on plants through various mechanisms such as nitrogen fixation, phosphate solubilisation, indole acetic acid and siderophore production and biofilm formation. These traits enhance plant growth and protect the host plant against parasitic organisms that are present in soil. The arbuscular mycorrhizal (AM) fungi are well known for their beneficial symbiotic effects on host plants. The objective of this study was to determine the role of AM fungi and associated beneficial rhizobacteria in improving the growth of V. erioloba seedlings. Soil and root samples were collected from a farm in the Northern Cape, South Africa. Fifty-seven bacterial cultures were isolated from the soil and tested for plant growth promoting characteristics. Fourteen isolates showing at least four beneficial traits were molecularly identified using the GenBank database. The AM fungal and bacterial populations in the soil samples were assessed using Illumina sequencing. Sequences were identified using the MaarJAM and GenBank databases, respectively. Three separate pot trials were conducted to determine; 1) the effects of cadmium (Cd) on seedling growth; 2) the individual effects of three selected bacterial isolates and AM fungi alone and combined on seedling growth, and 3) the combined effects of the selected bacteria on AM fungal inoculated and uninoculated seedlings. Of the fourteen isolates the Enterobacter genera was the dominant species identified, with Acinetobacter, Pantoea and Bacillus each having one isolate. All were described as plant growth promoting rhizobacteria. One isolate from each genus, excluding Pantoea, was used in the pot trials. Three genera were identified in the AM fungal population that was assessed, namely Ambispora, Paraglomus and Glomus with Ambispora being the dominant genus. The bacterial population assessed showed a high diversity of bacteria from the Actinobacteria phylum being the dominant group. The results of the heavy metal pot trial showed that the symbiotic relationship between the seedlings and AM fungi increased the seedlings’ health and growth during heavy metal stress. The combination of bacteria and AM fungi increased growth parameters in all the inoculated seedlings, but not when compared to uninoculated seedlings indicating a possible competition for nutrients. The results were influenced by the presence of a nematode, which was suspected to have been seed borne. Further investigations on these interactions are required. Inoculation of AM fungi and selected PGPR is recommended for V. erioloba seedling production. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2018
- Full Text:
- Authors: Van Aswegen, Sunet
- Date: 2018
- Subjects: Vesicular-arbuscular mycorrhizas , Cadmium , Rhizobacteria , Plant growth-promoting rhizobacteria , Acacia erioloba
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/63716 , vital:28475
- Description: Vachellia erioloba (camel thorn) is one of South Africa’s economically important tree species and therefore requires further investigation to improve its health and growth. Beneficial soil microbes have positive effects on plants through various mechanisms such as nitrogen fixation, phosphate solubilisation, indole acetic acid and siderophore production and biofilm formation. These traits enhance plant growth and protect the host plant against parasitic organisms that are present in soil. The arbuscular mycorrhizal (AM) fungi are well known for their beneficial symbiotic effects on host plants. The objective of this study was to determine the role of AM fungi and associated beneficial rhizobacteria in improving the growth of V. erioloba seedlings. Soil and root samples were collected from a farm in the Northern Cape, South Africa. Fifty-seven bacterial cultures were isolated from the soil and tested for plant growth promoting characteristics. Fourteen isolates showing at least four beneficial traits were molecularly identified using the GenBank database. The AM fungal and bacterial populations in the soil samples were assessed using Illumina sequencing. Sequences were identified using the MaarJAM and GenBank databases, respectively. Three separate pot trials were conducted to determine; 1) the effects of cadmium (Cd) on seedling growth; 2) the individual effects of three selected bacterial isolates and AM fungi alone and combined on seedling growth, and 3) the combined effects of the selected bacteria on AM fungal inoculated and uninoculated seedlings. Of the fourteen isolates the Enterobacter genera was the dominant species identified, with Acinetobacter, Pantoea and Bacillus each having one isolate. All were described as plant growth promoting rhizobacteria. One isolate from each genus, excluding Pantoea, was used in the pot trials. Three genera were identified in the AM fungal population that was assessed, namely Ambispora, Paraglomus and Glomus with Ambispora being the dominant genus. The bacterial population assessed showed a high diversity of bacteria from the Actinobacteria phylum being the dominant group. The results of the heavy metal pot trial showed that the symbiotic relationship between the seedlings and AM fungi increased the seedlings’ health and growth during heavy metal stress. The combination of bacteria and AM fungi increased growth parameters in all the inoculated seedlings, but not when compared to uninoculated seedlings indicating a possible competition for nutrients. The results were influenced by the presence of a nematode, which was suspected to have been seed borne. Further investigations on these interactions are required. Inoculation of AM fungi and selected PGPR is recommended for V. erioloba seedling production. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2018
- Full Text:
Yeast-baculovirus synergism: investigating mixed infections for improved management of the false codling moth, Thaumatotibia leucotreta
- Authors: Van der Merwe, Marcel
- Date: 2018
- Subjects: Cryptophlebia leucotreta , Baculoviruses , Yeast , Citrus Diseases and pests , Biological pest control agents , Pests Integrated control
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/62963 , vital:28347
- Description: Thaumatotibia leucotreta (Meyrick) (Lepidoptera: Tortricidae) or otherwise commonly known as the false codling moth is an indigenous pest of the citrus industry in southern Africa. The pest is highly significant as it impacts negatively on the export of fresh citrus fruits from South Africa to international markets. To control T. leucotreta in South Africa, an integrated pest management (IPM) programme has been implemented. One component of this programme is the baculovirus Cryptophlebia leucotreta granulovirus (CrleGV-SA) which has been formulated into the products Cryptogran™ and Cryptex®. It has previously been reported that there is a mutualistic association between Cydia pomonella (L.) (Lepidoptera: Tortricidae) also known as codling moth, and epiphytic yeasts. Cydia pomonella larval feeding galleries were colonised by yeasts and this, in turn, reduced larval mortality and enhanced larval development. It has been demonstrated in laboratory assays and field trials that combining yeast and brown cane sugar with Cydia pomonella granulovirus (CpGV) significantly increased larval mortality and lowered the proportion of injured apple fruit. This suggests that yeasts can enhance the effectiveness of an insect virus in managing pest larvae. In this study, we proposed to determine which species of yeast occur naturally in the digestive tract, frass and on the epidermis of T. leucotreta larvae and to examine whether any of these yeasts, when combined with the CrleGV-SA, have a synergistic effect in increasing mortality of T. leucotreta larvae. Firstly, Navel oranges infested with T. leucotreta larvae were collected from orchards in Sundays River Valley in Eastern Cape of South Africa. Larvae were extracted and analysed for the presence of yeast on their surface, or in their gut and frass. Four yeasts were isolated from T. leucotreta larvae and identified down to species level via PCR amplification and sequencing of internal transcribed spacer (ITS) region and D1/D2 domain of the large subunit (LSU) of rDNA region. These yeasts were isolated from the frass, epidermis and digestive tract of T. leucotreta larvae. The yeast isolates were identified as Meyerozyma caribbica, Pichia kluyveri, Pichia kudriavzevii and Hanseniaspora opuntiae. A yeast preference assay was conducted on female T. leucotreta moths to examine whether any of the isolated yeast species affected their oviposition preference. Navel oranges were inoculated with the isolated yeast species at a concentration of 6 × 108 cells.ml-1. The assay also included a Brewer’s yeast and distilled water control. Pichia kudriavzevii was shown to be the preferred yeast species for oviposition, as significantly more eggs were deposited on Navel oranges inoculated with this yeast compared to the other treatments. Lastly, a detached fruit bioassay was performed to evaluate the efficacy of mixing P. kudriavzevii with CrleGV-SA to enhance T. leucotreta larvae mortality. Pichia kudriavzevii was selected as it was demonstrated as having an effect on the oviposition preference of female T. leucotreta moths. The concentration at which P. kudriavzevii was applied remained the same as in the preference assay while CrleGV-SA was applied at lethal concentration required to kill 50 % of the population (9.31 × 107 OBs.ml-1). Although an increase in larval mortality was observed between CrleGV-SA being applied alone and the yeast/virus mixture, this result was determined not to be statistically significant. The experiments performed in this study provide a platform for further research into the application of a yeast-virus combination as a novel control option for T. leucotreta in the field. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2018
- Full Text:
- Authors: Van der Merwe, Marcel
- Date: 2018
- Subjects: Cryptophlebia leucotreta , Baculoviruses , Yeast , Citrus Diseases and pests , Biological pest control agents , Pests Integrated control
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/62963 , vital:28347
- Description: Thaumatotibia leucotreta (Meyrick) (Lepidoptera: Tortricidae) or otherwise commonly known as the false codling moth is an indigenous pest of the citrus industry in southern Africa. The pest is highly significant as it impacts negatively on the export of fresh citrus fruits from South Africa to international markets. To control T. leucotreta in South Africa, an integrated pest management (IPM) programme has been implemented. One component of this programme is the baculovirus Cryptophlebia leucotreta granulovirus (CrleGV-SA) which has been formulated into the products Cryptogran™ and Cryptex®. It has previously been reported that there is a mutualistic association between Cydia pomonella (L.) (Lepidoptera: Tortricidae) also known as codling moth, and epiphytic yeasts. Cydia pomonella larval feeding galleries were colonised by yeasts and this, in turn, reduced larval mortality and enhanced larval development. It has been demonstrated in laboratory assays and field trials that combining yeast and brown cane sugar with Cydia pomonella granulovirus (CpGV) significantly increased larval mortality and lowered the proportion of injured apple fruit. This suggests that yeasts can enhance the effectiveness of an insect virus in managing pest larvae. In this study, we proposed to determine which species of yeast occur naturally in the digestive tract, frass and on the epidermis of T. leucotreta larvae and to examine whether any of these yeasts, when combined with the CrleGV-SA, have a synergistic effect in increasing mortality of T. leucotreta larvae. Firstly, Navel oranges infested with T. leucotreta larvae were collected from orchards in Sundays River Valley in Eastern Cape of South Africa. Larvae were extracted and analysed for the presence of yeast on their surface, or in their gut and frass. Four yeasts were isolated from T. leucotreta larvae and identified down to species level via PCR amplification and sequencing of internal transcribed spacer (ITS) region and D1/D2 domain of the large subunit (LSU) of rDNA region. These yeasts were isolated from the frass, epidermis and digestive tract of T. leucotreta larvae. The yeast isolates were identified as Meyerozyma caribbica, Pichia kluyveri, Pichia kudriavzevii and Hanseniaspora opuntiae. A yeast preference assay was conducted on female T. leucotreta moths to examine whether any of the isolated yeast species affected their oviposition preference. Navel oranges were inoculated with the isolated yeast species at a concentration of 6 × 108 cells.ml-1. The assay also included a Brewer’s yeast and distilled water control. Pichia kudriavzevii was shown to be the preferred yeast species for oviposition, as significantly more eggs were deposited on Navel oranges inoculated with this yeast compared to the other treatments. Lastly, a detached fruit bioassay was performed to evaluate the efficacy of mixing P. kudriavzevii with CrleGV-SA to enhance T. leucotreta larvae mortality. Pichia kudriavzevii was selected as it was demonstrated as having an effect on the oviposition preference of female T. leucotreta moths. The concentration at which P. kudriavzevii was applied remained the same as in the preference assay while CrleGV-SA was applied at lethal concentration required to kill 50 % of the population (9.31 × 107 OBs.ml-1). Although an increase in larval mortality was observed between CrleGV-SA being applied alone and the yeast/virus mixture, this result was determined not to be statistically significant. The experiments performed in this study provide a platform for further research into the application of a yeast-virus combination as a novel control option for T. leucotreta in the field. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2018
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Composition and fate of triclosan in the sludge from wastewater treatment in Grahamstown, South Africa and Tiaret, Algeria
- Authors: Ncube, Mbonisi
- Date: 2017
- Subjects: Sewage sludge , Sewage Purification South Africa Grahamstown , Sewage Purification Algeria Tiaret , Sewage sludge as fertilizer , Anti-infective agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/65156 , vital:28697
- Description: Physicochemical properties such as pH, specific surface area (SSA), cationic exchange capacity (CEC), loss on ignition (LOI), pathogens, plant nutrients (nitrates, ammonium and phosphates), and heavy metals (manganese, copper, lead and cadmium) were determined for sewage sludge from Grahamstown and Tiaret. The values obtained were log transformed thereafter a t-test at 5 % level of significance was used to test for the difference in each parameter for both sludges. The pH of sludge was determined in 1:3 water, 16 water, 1:3 0.01 M calcium chloride and 1:3 1 M potassium chloride. The pH for Grahamstown and Tiaret sludge were in the ranges of 6.66-7.11 and 7.88-8.18 respectively. The SSA values for Grahamstown and Tiaret were 218 ± 108 and 261 ± 99.9 m2/g, and the CEC values were 119 ± 2.09 and 136 ± 6.03 mEq/100, respectively. The LOI values obtained were 1.33 ± 0.03 and 1.48 ± 0.11 % for Grahamstown and Tiaret, respectively. E. coll and heterotrophic bacteria were the pathogens determined, and were extracted from sludge using sterile saline and nutrient broth. The concentration of E. coll in Grahamstown and Tiaret sludge were 468 ± 7.63 and 7769 ± 1268 CFU/g d.w and for heterotrophic bacteria were 1.17x109 ± 7.42x108 and 1.43x109 ± 9.11 x108 CFU/g d.w. For Grahamstown sludge, the concentration of nitrates, ammonium and phosphates were 55.61 ± 55.20 mg/g d.w, 6.60 ± 2.36 mg/g d.w and 1.40 ± 0.30 mg/g d.w, respectively. For Tiaret sludge, the concentration of nitrates, ammonium and phosphates were 2.56 ± 2.90 mg/g d.w, 0.64 ± 0.45 mg/g d.w and 0.24 ± 0.19 mg/g d.w, respectively. The concentration of Mn, Cu, Pb and Cd in Grahamstown sludge were 423 ± 101, 353 ± 92, 40.2 ± 20 and 0.0 mg/kg d.w respectively, and for Tiaret sludge, the corresponding concentrations were 358± 295, 549±50, 1427± 1352 and 1.54 ± 0.61 mg/kg d.w. Sewage sludge was found to contain Triclosan, and solubility studies of the compound were conducted using sodium deoxycholate and sodium lithocholate. The apparent solubilities and rate constants indicated in brackets of TCS at 37 °C were 35.4 ± 1.21 mg/L (1.28 ± 0.36 Hr-) and 14.4 ± 0.34 mg/L (0.99 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. The apparent solubilities and rate constants indicated in brackets of TCS at 15 °C were 32.3 ± 0.88 mg/L (2.16 ± 0.80 Hr-) and 14.2 ± 0.39 mg/L (1.02 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. Triclosan was extracted from sludge using 1 g/L sodium deoxycholate and the determined concentration were 142 ± 33.5 gg/g d.w for Grahamstown sludge and 0-12 gg/g d.w for Tiaret sludge. Finally plant growth studies were conducted on radish and garden cress plants using Grahamstown sludge at 0, 20, 40, 80 and 100 % treatments. Statistical analysis (t-test and Kruskal-Wallis) at 5 % level of significance was done to compare growth parameters between control and different sludge treatments. For radish plants, the values for plant height, root length, number of leaves, leaf length and dry mass were 28.4-80-7 mm, 4.3-44.7 mm, 3.3-17.0 mm, 2.3-4.0 leaves and 6.3-15.3 %, respectively. For garden cress, the values for plant height, root length, number of leaves, leaf length and dry mass were 13.7-25.0 mm, 7.7-20.3 mm, 5.7-8.3 leaves, 3.0-8.3 mm and 8.8-15.0 %, respectively. Twenty percent (20 %) sludge treatment gave the best results in radish and garden cress plants with respect to plant height, root length, number of leaves and dry mass. Triclosan concentration in radish and garden cress plants was below the detection limit of 32.4 gg/g d.w. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
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- Authors: Ncube, Mbonisi
- Date: 2017
- Subjects: Sewage sludge , Sewage Purification South Africa Grahamstown , Sewage Purification Algeria Tiaret , Sewage sludge as fertilizer , Anti-infective agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/65156 , vital:28697
- Description: Physicochemical properties such as pH, specific surface area (SSA), cationic exchange capacity (CEC), loss on ignition (LOI), pathogens, plant nutrients (nitrates, ammonium and phosphates), and heavy metals (manganese, copper, lead and cadmium) were determined for sewage sludge from Grahamstown and Tiaret. The values obtained were log transformed thereafter a t-test at 5 % level of significance was used to test for the difference in each parameter for both sludges. The pH of sludge was determined in 1:3 water, 16 water, 1:3 0.01 M calcium chloride and 1:3 1 M potassium chloride. The pH for Grahamstown and Tiaret sludge were in the ranges of 6.66-7.11 and 7.88-8.18 respectively. The SSA values for Grahamstown and Tiaret were 218 ± 108 and 261 ± 99.9 m2/g, and the CEC values were 119 ± 2.09 and 136 ± 6.03 mEq/100, respectively. The LOI values obtained were 1.33 ± 0.03 and 1.48 ± 0.11 % for Grahamstown and Tiaret, respectively. E. coll and heterotrophic bacteria were the pathogens determined, and were extracted from sludge using sterile saline and nutrient broth. The concentration of E. coll in Grahamstown and Tiaret sludge were 468 ± 7.63 and 7769 ± 1268 CFU/g d.w and for heterotrophic bacteria were 1.17x109 ± 7.42x108 and 1.43x109 ± 9.11 x108 CFU/g d.w. For Grahamstown sludge, the concentration of nitrates, ammonium and phosphates were 55.61 ± 55.20 mg/g d.w, 6.60 ± 2.36 mg/g d.w and 1.40 ± 0.30 mg/g d.w, respectively. For Tiaret sludge, the concentration of nitrates, ammonium and phosphates were 2.56 ± 2.90 mg/g d.w, 0.64 ± 0.45 mg/g d.w and 0.24 ± 0.19 mg/g d.w, respectively. The concentration of Mn, Cu, Pb and Cd in Grahamstown sludge were 423 ± 101, 353 ± 92, 40.2 ± 20 and 0.0 mg/kg d.w respectively, and for Tiaret sludge, the corresponding concentrations were 358± 295, 549±50, 1427± 1352 and 1.54 ± 0.61 mg/kg d.w. Sewage sludge was found to contain Triclosan, and solubility studies of the compound were conducted using sodium deoxycholate and sodium lithocholate. The apparent solubilities and rate constants indicated in brackets of TCS at 37 °C were 35.4 ± 1.21 mg/L (1.28 ± 0.36 Hr-) and 14.4 ± 0.34 mg/L (0.99 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. The apparent solubilities and rate constants indicated in brackets of TCS at 15 °C were 32.3 ± 0.88 mg/L (2.16 ± 0.80 Hr-) and 14.2 ± 0.39 mg/L (1.02 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. Triclosan was extracted from sludge using 1 g/L sodium deoxycholate and the determined concentration were 142 ± 33.5 gg/g d.w for Grahamstown sludge and 0-12 gg/g d.w for Tiaret sludge. Finally plant growth studies were conducted on radish and garden cress plants using Grahamstown sludge at 0, 20, 40, 80 and 100 % treatments. Statistical analysis (t-test and Kruskal-Wallis) at 5 % level of significance was done to compare growth parameters between control and different sludge treatments. For radish plants, the values for plant height, root length, number of leaves, leaf length and dry mass were 28.4-80-7 mm, 4.3-44.7 mm, 3.3-17.0 mm, 2.3-4.0 leaves and 6.3-15.3 %, respectively. For garden cress, the values for plant height, root length, number of leaves, leaf length and dry mass were 13.7-25.0 mm, 7.7-20.3 mm, 5.7-8.3 leaves, 3.0-8.3 mm and 8.8-15.0 %, respectively. Twenty percent (20 %) sludge treatment gave the best results in radish and garden cress plants with respect to plant height, root length, number of leaves and dry mass. Triclosan concentration in radish and garden cress plants was below the detection limit of 32.4 gg/g d.w. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
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Development and assessment of gastric-retentive sustained release metronidazole microcapsules
- Authors: Makan, Anjana
- Date: 2017
- Subjects: Metronidazole , Drug delivery systems , Helicobacter pylori , High performance liquid chromatography , Gas chromatography , Drugs , Drugs Controlled release
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59240 , vital:27491
- Description: Helicobacter pylori is one of the most common pathogenic bacterial infections and is the leading cause of gastritis, gastroduodenal ulcer disease and gastric cancers. Studies have revealed the prevalence of Helicobacter pylori is high in many countries around the globe. Although Helicobacter pylori is highly sensitive to antimicrobial agents in vitro the clinical eradication rate of the disease is still low. The instability of API at gastric pH, low concentration of API in the gastric mucosa and short gastric residence times are the main reasons for poor eradication rates. The high prevalence rate of this disease necessitates the design and development of gastric-retentive site specific oral dosage forms for the optimized delivery of existing therapeutic molecules and may be an approach to improving the eradication rate of Helicobacter pylori. Metronidazole (MTZ) is a 5-nitroimidazole derivative that exhibits antibiotic and antiprotozoal activity. MTZ is used in combination with other compounds for the treatment of Helicobacter pylori in peptic ulcer disease. MTZ is a potential candidate for inclusion in a sustained release gastric-retentive delivery system that acts in the stomach and since it is unstable in the intestinal/colonic environment enhancing gastric residence time would be a therapeutic advantage. MTZ is a cost-effective therapy that exhibits good anti-microbial activity and has a favourable pharmacokinetic profile. A sustained release gastric-retentive formulation is therefore proposed as an approach to enhance the local delivery of MTZ and improve treatment outcomes for patients infected with Helicobacter pylori. A stability indicating Reversed-Phase High Performance Liquid Chromatography (RP- HPLC) method for the quantitation of MTZ in pharmaceutical dosage forms was developed and optimised using a Central Composite Design (CCD) approach. The RP-HPLC method was found to be linear, accurate, precise, sensitive, selective, and was applied to the analysis of MTZ in commercially available medicines. Preformulation studies were conducted as preparative work prior to manufacture gastric- retentive sustained release MTZ microcapsules. The experiments conducted were tailored for the development of sustained release MTZ microcapsules using a solvent evaporation method. The particle size and shape of the microcapsules was investigated using Scanning Electron Microscopy (SEM). MTZ- excipient compatibility studies were performed using Fourier Transform Infra-red Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD). The results revealed that no definite interaction between MTZ and intended excipients to be used for manufacture of MTZ formulations occurred. A solvent evaporation procedure was used for the manufacture of MTZ microcapsules. Preliminary formulations were manufactured using two different grades of Methocel® at various levels. In addition the impact of processing parameters on performance was also investigated. The formulations were assessed in terms of in vitro release, buoyancy, yield, encapsulation efficiency and microcapsule size. Formulation optimisation was undertaken using a CCD approach and numerical optimisation was used to predict an optimised formulation composition that would produce minimal initial MTZ release, maximum MTZ release at 12 hours and maximum buoyancy, encapsulation efficiency and yield. The kinetics of MTZ release from microcapsules was established by fitting in vitro release data to different mathematical models. Higuchi model and first-order model appeared to best fit the data as majority of the formulation batches had highest R2 values for these models. Short-term stability assessment of the optimised formulation was established by undertaking stability studies at 25°C/60% RH and 40°C/75%RH. No significant changes in any of the CQA were observed over 30 days of stability testing. A gas chromatographic (GC) method was developed and validated for the quantitation of residual acetone and n-hexane. The optimised formulation contained 213.60 ppm/g acetone and 25.23 ppm/g n-hexane which are well below the limits set for residual solvents. In conclusion, gastric-retentive sustained release MTZ microcapsules with potential for further development and optimisation have been successfully developed and assessed in these studies. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Authors: Makan, Anjana
- Date: 2017
- Subjects: Metronidazole , Drug delivery systems , Helicobacter pylori , High performance liquid chromatography , Gas chromatography , Drugs , Drugs Controlled release
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59240 , vital:27491
- Description: Helicobacter pylori is one of the most common pathogenic bacterial infections and is the leading cause of gastritis, gastroduodenal ulcer disease and gastric cancers. Studies have revealed the prevalence of Helicobacter pylori is high in many countries around the globe. Although Helicobacter pylori is highly sensitive to antimicrobial agents in vitro the clinical eradication rate of the disease is still low. The instability of API at gastric pH, low concentration of API in the gastric mucosa and short gastric residence times are the main reasons for poor eradication rates. The high prevalence rate of this disease necessitates the design and development of gastric-retentive site specific oral dosage forms for the optimized delivery of existing therapeutic molecules and may be an approach to improving the eradication rate of Helicobacter pylori. Metronidazole (MTZ) is a 5-nitroimidazole derivative that exhibits antibiotic and antiprotozoal activity. MTZ is used in combination with other compounds for the treatment of Helicobacter pylori in peptic ulcer disease. MTZ is a potential candidate for inclusion in a sustained release gastric-retentive delivery system that acts in the stomach and since it is unstable in the intestinal/colonic environment enhancing gastric residence time would be a therapeutic advantage. MTZ is a cost-effective therapy that exhibits good anti-microbial activity and has a favourable pharmacokinetic profile. A sustained release gastric-retentive formulation is therefore proposed as an approach to enhance the local delivery of MTZ and improve treatment outcomes for patients infected with Helicobacter pylori. A stability indicating Reversed-Phase High Performance Liquid Chromatography (RP- HPLC) method for the quantitation of MTZ in pharmaceutical dosage forms was developed and optimised using a Central Composite Design (CCD) approach. The RP-HPLC method was found to be linear, accurate, precise, sensitive, selective, and was applied to the analysis of MTZ in commercially available medicines. Preformulation studies were conducted as preparative work prior to manufacture gastric- retentive sustained release MTZ microcapsules. The experiments conducted were tailored for the development of sustained release MTZ microcapsules using a solvent evaporation method. The particle size and shape of the microcapsules was investigated using Scanning Electron Microscopy (SEM). MTZ- excipient compatibility studies were performed using Fourier Transform Infra-red Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD). The results revealed that no definite interaction between MTZ and intended excipients to be used for manufacture of MTZ formulations occurred. A solvent evaporation procedure was used for the manufacture of MTZ microcapsules. Preliminary formulations were manufactured using two different grades of Methocel® at various levels. In addition the impact of processing parameters on performance was also investigated. The formulations were assessed in terms of in vitro release, buoyancy, yield, encapsulation efficiency and microcapsule size. Formulation optimisation was undertaken using a CCD approach and numerical optimisation was used to predict an optimised formulation composition that would produce minimal initial MTZ release, maximum MTZ release at 12 hours and maximum buoyancy, encapsulation efficiency and yield. The kinetics of MTZ release from microcapsules was established by fitting in vitro release data to different mathematical models. Higuchi model and first-order model appeared to best fit the data as majority of the formulation batches had highest R2 values for these models. Short-term stability assessment of the optimised formulation was established by undertaking stability studies at 25°C/60% RH and 40°C/75%RH. No significant changes in any of the CQA were observed over 30 days of stability testing. A gas chromatographic (GC) method was developed and validated for the quantitation of residual acetone and n-hexane. The optimised formulation contained 213.60 ppm/g acetone and 25.23 ppm/g n-hexane which are well below the limits set for residual solvents. In conclusion, gastric-retentive sustained release MTZ microcapsules with potential for further development and optimisation have been successfully developed and assessed in these studies. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
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