Identification of differentially expressed proteins involved in wheat (Triticum aestivum) resistance against Russian Wheat Aphid (Diuraphis noxia) SA2 using SWATH-MS analysis
- Authors: Ntlokwana, Sitha Emmanuel
- Date: 2020
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10353/18872 , vital:42888
- Description: Wheat (Triticum aestivum) is the second most-consumed cereal crop in the world, second only to maize. In South Africa it is mainly produced in three provinces; the Free State, Western Cape, and the Northen Cape. The average total land area used for wheat cultivation in these three Provinces, is 533 000 hectares, with a resultant annual production of between 1.3 to 2 million tons. The total wheat requirement in South Africa is currently 2.7 million tons according to the production of wheat guidelines published by the Department of Agriculture, Forestry and Fisheries, which is higher than the total annual production. One of the primary reasons that contribute to the lower production levels is insect and pest infestation, in particular, the Russian wheat aphid (Diurophis noxis), which can result in crop loss of up to sixty percent. Russian wheat aphids (RWA) are invasive insects that feed on the phloem of the plant through their specialised thin stylet-like mouthparts and release toxic agents contained in their saliva during feeding, which disrupt cellular functions inside the host plant. This damage leads to symptoms like; chlorosis, necrosis, wilting, stunting and curling of leaves, also known as leaf rolling. This study aimed to identify differentially expressed proteins in resistant and susceptible wheat (Triticum aestivum) cultivars during Russian wheat aphid Biotype South African 2 (RWA-SA2) infestation, in order to identify proteins involved in the wheat resistant mechanism against RWA-SA2. Two wheat cultivars SST398 (resistant to RWA-SA2) and SST356 (susceptible to RWA-SA2) were used, and a total number of 126 plants were planted and divided according to four different harvest times (Control day 0; day 5; day 7 and day 12). The wheat plants were infested with approximately 10 aphids per plant at the three-leaf stage, and placed within an insect cage inside a growth chamber (Conviron, Winnipeg, Canada) set at 24ºC, light intensity of 352 µmol.m-2.sec-1, ambient CO2 levels (410 ppm) and humidity of 60% with a 16h/8h day/night cycle. Wheat leaves were harvested at various time frames, and total protein extraction was performed. The protein samples were reduced with 10 mM dithiothreitol (DTT) and alkylated with 30 mM iodoacetamide (IAA). Sample clean-up and on-bead trypsin digest were performed on megReSyn Hilic columns, over four hours. The resultant peptides were vacuum dried and resuspended in 2% acetonitrile (ACN) before submitting them to LC-MS/MS (SWATH) for analysis. A total number of 611 proteins were differentially expressed, of which 19 were identified to be involved in the resistance response of wheat, and an additional 20 involved in biotic stress responses. This study showed that reactive oxidative species (ROS) such as hydrogen peroxide and hydroxyl radicals (OH-) play a significant role in the early stages of wheat resistance against RWA-SA2 infestation. They are involved in cell wall strengthening, activation of defence genes, involvement of phytohormone signals such as salicylic and jasmonic acid, which also mediates the systemic defences such as, systemic acquired resistance (SAR), leading to the expression of pathogen-related proteins such as (thaumatin-like proteins, oxalate oxidase, defensin, chitinase, and thionins). Although up-regulation of photosynthesis proteins such as (chlorophyll a/b binding protein, photosystem I and II, rubisco and divinyl chlorophyllide a, and 8 vinyl-reductase) were seen on both infested cultivars (susceptible and resistance), higher numbers of these classes of proteins were identified in the resistance cultivar, suggesting that they also play a critical role in resistance. In conclusion, the SWATH analysis used in this study was able to identify numerous proteins involved in the wheat resistance mechanism against RWA-SA2, most of which have not yet been reported to be involved in either biotic stress or RWA-SA2 resistance responses. Future studies are required to biochemically confirm the involvement of these enzymes and proteins the specific metabolic pathways where they are found, in the wheat resistance mechanism against Russian wheat aphid Biotype 2
- Full Text:
- Date Issued: 2020
- Authors: Ntlokwana, Sitha Emmanuel
- Date: 2020
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10353/18872 , vital:42888
- Description: Wheat (Triticum aestivum) is the second most-consumed cereal crop in the world, second only to maize. In South Africa it is mainly produced in three provinces; the Free State, Western Cape, and the Northen Cape. The average total land area used for wheat cultivation in these three Provinces, is 533 000 hectares, with a resultant annual production of between 1.3 to 2 million tons. The total wheat requirement in South Africa is currently 2.7 million tons according to the production of wheat guidelines published by the Department of Agriculture, Forestry and Fisheries, which is higher than the total annual production. One of the primary reasons that contribute to the lower production levels is insect and pest infestation, in particular, the Russian wheat aphid (Diurophis noxis), which can result in crop loss of up to sixty percent. Russian wheat aphids (RWA) are invasive insects that feed on the phloem of the plant through their specialised thin stylet-like mouthparts and release toxic agents contained in their saliva during feeding, which disrupt cellular functions inside the host plant. This damage leads to symptoms like; chlorosis, necrosis, wilting, stunting and curling of leaves, also known as leaf rolling. This study aimed to identify differentially expressed proteins in resistant and susceptible wheat (Triticum aestivum) cultivars during Russian wheat aphid Biotype South African 2 (RWA-SA2) infestation, in order to identify proteins involved in the wheat resistant mechanism against RWA-SA2. Two wheat cultivars SST398 (resistant to RWA-SA2) and SST356 (susceptible to RWA-SA2) were used, and a total number of 126 plants were planted and divided according to four different harvest times (Control day 0; day 5; day 7 and day 12). The wheat plants were infested with approximately 10 aphids per plant at the three-leaf stage, and placed within an insect cage inside a growth chamber (Conviron, Winnipeg, Canada) set at 24ºC, light intensity of 352 µmol.m-2.sec-1, ambient CO2 levels (410 ppm) and humidity of 60% with a 16h/8h day/night cycle. Wheat leaves were harvested at various time frames, and total protein extraction was performed. The protein samples were reduced with 10 mM dithiothreitol (DTT) and alkylated with 30 mM iodoacetamide (IAA). Sample clean-up and on-bead trypsin digest were performed on megReSyn Hilic columns, over four hours. The resultant peptides were vacuum dried and resuspended in 2% acetonitrile (ACN) before submitting them to LC-MS/MS (SWATH) for analysis. A total number of 611 proteins were differentially expressed, of which 19 were identified to be involved in the resistance response of wheat, and an additional 20 involved in biotic stress responses. This study showed that reactive oxidative species (ROS) such as hydrogen peroxide and hydroxyl radicals (OH-) play a significant role in the early stages of wheat resistance against RWA-SA2 infestation. They are involved in cell wall strengthening, activation of defence genes, involvement of phytohormone signals such as salicylic and jasmonic acid, which also mediates the systemic defences such as, systemic acquired resistance (SAR), leading to the expression of pathogen-related proteins such as (thaumatin-like proteins, oxalate oxidase, defensin, chitinase, and thionins). Although up-regulation of photosynthesis proteins such as (chlorophyll a/b binding protein, photosystem I and II, rubisco and divinyl chlorophyllide a, and 8 vinyl-reductase) were seen on both infested cultivars (susceptible and resistance), higher numbers of these classes of proteins were identified in the resistance cultivar, suggesting that they also play a critical role in resistance. In conclusion, the SWATH analysis used in this study was able to identify numerous proteins involved in the wheat resistance mechanism against RWA-SA2, most of which have not yet been reported to be involved in either biotic stress or RWA-SA2 resistance responses. Future studies are required to biochemically confirm the involvement of these enzymes and proteins the specific metabolic pathways where they are found, in the wheat resistance mechanism against Russian wheat aphid Biotype 2
- Full Text:
- Date Issued: 2020
The cultural practice of child marriage as a challenge to the realisation of the human rights of the girl –child: a comparative study of South Africa and Nigeria
- Authors: Olaborede, Adebola Olufunmi
- Date: 2016
- Subjects: Forced marriage Teenage marriage Children's rights Rites and ceremonies
- Language: English
- Type: Thesis , Doctoral , Law
- Identifier: http://hdl.handle.net/10353/2578 , vital:27898
- Description: This study primarily sets out to examine the cultural practice of child marriage in Africa with a focus on the comparative study of South Africa and Nigeria. This practice has been prohibited in a number of international human rights instruments such as the African Charter on the Rights and Welfare of the Child, and the Protocol to the African Charter on Human and Peoples’ Right on the Rights of Women in Africa. However, overwhelming statistics show that the overall prevalence of child marriage in Africa is still very high and if current trends continue, Africa will become a region with the largest number of the global share of child marriages, by 2050. Different interconnecting factors promote and reinforce child marriage which makes this practice very complex. The challenge of cultural traditional practices and religious beliefs that promote child marriage in Africa are evaluated in this study. The complexities surrounding these cultural practices mainly relate to the conflict that exists between adhering to customs and traditional practices, and promoting the practical implementations and enforcement of human rights standards within communities. In particular, the age at which most girls are given out in marriage conflicts with the minimum legal age of marriage, lack of free and full consent to marriage and the mixed legal system, which mainly comprises of customary law, Islamic law and common or civil law and legislation, that often conflict with one another in most African States. Discussions on these contradictions, as in the case of child marriage, often lead to a seemingly endless debate between the universality of human rights and cultural relativism within African societies. Therefore, this study bears heavily on the debate and relationship between culture and human rights, and the extent to which they can be reconciled in order to achieve a realisation of the fundamental rights of the girl-child. A qualitative research method based on an extensive literature analysis from different disciples is adopted. In addition, is a comparative study of South Africa and Nigeria which seeks to provide insight into the nature and extent of the practice of child marriage, as well as evaluate the adequacy, effectiveness and shortcomings of national legislations that relate to the rights of a girl-child in the context of child marriage, in both jurisdictions.
- Full Text:
- Date Issued: 2016
- Authors: Olaborede, Adebola Olufunmi
- Date: 2016
- Subjects: Forced marriage Teenage marriage Children's rights Rites and ceremonies
- Language: English
- Type: Thesis , Doctoral , Law
- Identifier: http://hdl.handle.net/10353/2578 , vital:27898
- Description: This study primarily sets out to examine the cultural practice of child marriage in Africa with a focus on the comparative study of South Africa and Nigeria. This practice has been prohibited in a number of international human rights instruments such as the African Charter on the Rights and Welfare of the Child, and the Protocol to the African Charter on Human and Peoples’ Right on the Rights of Women in Africa. However, overwhelming statistics show that the overall prevalence of child marriage in Africa is still very high and if current trends continue, Africa will become a region with the largest number of the global share of child marriages, by 2050. Different interconnecting factors promote and reinforce child marriage which makes this practice very complex. The challenge of cultural traditional practices and religious beliefs that promote child marriage in Africa are evaluated in this study. The complexities surrounding these cultural practices mainly relate to the conflict that exists between adhering to customs and traditional practices, and promoting the practical implementations and enforcement of human rights standards within communities. In particular, the age at which most girls are given out in marriage conflicts with the minimum legal age of marriage, lack of free and full consent to marriage and the mixed legal system, which mainly comprises of customary law, Islamic law and common or civil law and legislation, that often conflict with one another in most African States. Discussions on these contradictions, as in the case of child marriage, often lead to a seemingly endless debate between the universality of human rights and cultural relativism within African societies. Therefore, this study bears heavily on the debate and relationship between culture and human rights, and the extent to which they can be reconciled in order to achieve a realisation of the fundamental rights of the girl-child. A qualitative research method based on an extensive literature analysis from different disciples is adopted. In addition, is a comparative study of South Africa and Nigeria which seeks to provide insight into the nature and extent of the practice of child marriage, as well as evaluate the adequacy, effectiveness and shortcomings of national legislations that relate to the rights of a girl-child in the context of child marriage, in both jurisdictions.
- Full Text:
- Date Issued: 2016
Reading identities: a case study of grade 8 learners' interactions in a reading club
- Scheckle, Eileen Margaret Agnes
- Authors: Scheckle, Eileen Margaret Agnes
- Date: 2015
- Subjects: Group reading -- South Africa , Reading (Middle school) -- South Africa , Literacy programs -- South Africa , Identity (Psychology) in adolescence , Identity (Psychology) in adolescence -- South Africa , Discourse analysis -- Social aspects , Critical realism
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:1329 , http://hdl.handle.net/10962/d1017766
- Description: This study offers an account of reading clubs as a literacy intervention in a grade 8 English class at a former ‘Coloured’ high school in South Africa. Using Margaret Archer’s social realist methodology, it examines different practices of ‘reading’ used by learners in talking and writing about text. Archer’s analytical dualism and morphogenetic model provided an explanatory framework for this study. Analytical dualism allows for the separation of the parts (structural and cultural elements) from the people (the grade 8 learners) so as to analyse the interplay between structure and culture. The morphogenetic model recognises that antecedent structures predate this, and any study but that through the exercise of agency, morphogenesis, in the form of structural elaboration or morphostasis in the form of continuity, may occur. This study used a New Literacies perspective based on an ideological model of literacy which recognises many different literacies, in addition to dominant school literacies. Learners’ talk about books as well as personal journal writing provided an insight into what cultural mechanisms and powers children bring to the reading of novels. Understandings of discourses as well as of Gee’s (1990; 2008) construct of Discourse provided a framework for examining learners’ identities and shifts as readers. The data in this study, which is presented through a series of vignettes, found that grade 8 learners use many different experiences and draw on different discourses when making sense of texts. Through the separation of the structural and cultural components, this research could explore how reading clubs as structures enabled learners to access different discourses from the domain of culture. Through the process and engagement in the reading clubs, following Gee (2000b), learners were attributed affinity, discoursal and institutional identities as readers. It was found, in the course of the study, that providing a safe space, scaffolding, multiple opportunities to practice and a variety of reading material, helped learners to access and appropriate dominant literacies. In addition, learners need a repertoire of literacy practices to draw from as successful reading needs flexibility and adaptability. Reading and writing inform each other and through gradual induction into literary writing, learners began to appropriate and approximate dominant literacy practices. Following others who have contributed to the field of New Literacy Studies (Heath, 1983; Street, 1984; Gee 1990; Prinsloo & Breier, 1996), this study would suggest that literacies of traditionally underserved communities should not be considered in deficit terms. Instead these need to be understood as resources for negotiating meaning making and as tools or mechanisms to access dominant discourse practices. In addition the resilience and competition from Discourses of popular culture need to be recognised and developed as tools to access school literacies.
- Full Text:
- Date Issued: 2015
- Authors: Scheckle, Eileen Margaret Agnes
- Date: 2015
- Subjects: Group reading -- South Africa , Reading (Middle school) -- South Africa , Literacy programs -- South Africa , Identity (Psychology) in adolescence , Identity (Psychology) in adolescence -- South Africa , Discourse analysis -- Social aspects , Critical realism
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:1329 , http://hdl.handle.net/10962/d1017766
- Description: This study offers an account of reading clubs as a literacy intervention in a grade 8 English class at a former ‘Coloured’ high school in South Africa. Using Margaret Archer’s social realist methodology, it examines different practices of ‘reading’ used by learners in talking and writing about text. Archer’s analytical dualism and morphogenetic model provided an explanatory framework for this study. Analytical dualism allows for the separation of the parts (structural and cultural elements) from the people (the grade 8 learners) so as to analyse the interplay between structure and culture. The morphogenetic model recognises that antecedent structures predate this, and any study but that through the exercise of agency, morphogenesis, in the form of structural elaboration or morphostasis in the form of continuity, may occur. This study used a New Literacies perspective based on an ideological model of literacy which recognises many different literacies, in addition to dominant school literacies. Learners’ talk about books as well as personal journal writing provided an insight into what cultural mechanisms and powers children bring to the reading of novels. Understandings of discourses as well as of Gee’s (1990; 2008) construct of Discourse provided a framework for examining learners’ identities and shifts as readers. The data in this study, which is presented through a series of vignettes, found that grade 8 learners use many different experiences and draw on different discourses when making sense of texts. Through the separation of the structural and cultural components, this research could explore how reading clubs as structures enabled learners to access different discourses from the domain of culture. Through the process and engagement in the reading clubs, following Gee (2000b), learners were attributed affinity, discoursal and institutional identities as readers. It was found, in the course of the study, that providing a safe space, scaffolding, multiple opportunities to practice and a variety of reading material, helped learners to access and appropriate dominant literacies. In addition, learners need a repertoire of literacy practices to draw from as successful reading needs flexibility and adaptability. Reading and writing inform each other and through gradual induction into literary writing, learners began to appropriate and approximate dominant literacy practices. Following others who have contributed to the field of New Literacy Studies (Heath, 1983; Street, 1984; Gee 1990; Prinsloo & Breier, 1996), this study would suggest that literacies of traditionally underserved communities should not be considered in deficit terms. Instead these need to be understood as resources for negotiating meaning making and as tools or mechanisms to access dominant discourse practices. In addition the resilience and competition from Discourses of popular culture need to be recognised and developed as tools to access school literacies.
- Full Text:
- Date Issued: 2015
Knowledge and knowing in the public management and public administration programmes at a comprehensive university
- Authors: Lück, Jacqueline Catherine
- Date: 2014
- Subjects: Knowledge and learning , Public administration -- Study and teaching (Higher) , Knowledge, Sociology of , Learning, Psychology of , Knowledge, Theory of , Educational equalization -- South Africa , Education, Higher -- South Africa , Literacy -- South Africa , Technical institutes -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:1326 , http://hdl.handle.net/10962/d1013166
- Description: Knowledge is often tacit and under researched in educational fields. In order for student access to knowledge and its related academic discourses to be facilitated, a deep understanding needs to be gained of the form that this knowledge takes. This study interrogates the ways in which knowledge is constituted in the first year of a Public Management Diploma and a Public Administration Degree at a comprehensive university in South Africa. The study takes a social realist approach that understands reality as fact but sees our knowledge thereof as a social phenomenon. The study was concerned with knowledge structures and knower structures as it argues that these have not been adequately accounted for in the sociology of education research. But this study comes to this concern from a strongly ideological view of student reading and writing. This study calls on a social practices approach that sees literacy as embedded within specific academic discourses, which vary from context to context. It uses this ideological understanding of literacy as the orienting framework for the study of knowledge. The study takes place in a Higher Education mileu that has begun to transform from its divisive past. The transformation brought about new institutional formations such as the comprehensive university, with its mix of vocational, professional and formative programmes and varied emphasis on contextual and conceptual curriculum coherence. Increasingly, the transformation agenda also shifts concern from simply providing physical access to a previously disenfranchised majority to ensuring full participation in the context of high attrition rates in first year and low retention rates. The data was analysed using the Specialisation Codes of Legitimation Code Theory to see what was being specialised in the Diploma and Degree curricula of the Public Management and Administration fields. These fields are characterised in the literature by ongoing tensions about focus, and perceptions of there being a theoretical vacuum and an inability to deal adequately with challenges in the South African public sector. Analysis of lecturer interviews and first-year curriculum documentation showed that both the Public Management Diploma and Public Administration Degree have stronger epistemic relations (ER), with an emphasis on claims to knowledge of the world. The data showed relatively weak social relations (SR), in that there was not the valuing of a particular lens on the world or a specific disposition required for legitimation within this field. The combination of ER+ and SR- indicates that these curricula are Knowledge Codes, where legitimation is through the acquisition of a set of skills and procedures. The programmes were characterised by fairly low-level procedural knowledge, which may point to a workplace-oriented direction that is dominant in the comprehensive university. In keeping with concerns raised in the literature about this field, there was little evidence of theoretical or propositional knowledge in the Public Management Diploma and while the Public Administration Degree had some evidence of this, it was arguably not to the extent expected of a degree as described in the National Qualifications Framework. This study was limited to the first-year of the Diploma and Degree and subsequent years could present different findings. Lecturers showed awareness of student challenges with literacy practices and made concerned attempts through various interventions to address this but they were found to value the surface features of writing practices over personal engagement with the knowledge. Though the expectations of student literacy practices in tests and assignments were aligned to the ways in which knowledge was constructed in the curriculum, there was little evidence of student induction into disciplinary discourses of the field as knowledge was presented as being neutral and student writing primarily took the form of retelling objective facts. The implications of these findings could include student exclusion from higher-level academic discourse, more powerful knowledge in the workplace and, finally, constrain them from becoming producers of knowledge.
- Full Text:
- Date Issued: 2014
- Authors: Lück, Jacqueline Catherine
- Date: 2014
- Subjects: Knowledge and learning , Public administration -- Study and teaching (Higher) , Knowledge, Sociology of , Learning, Psychology of , Knowledge, Theory of , Educational equalization -- South Africa , Education, Higher -- South Africa , Literacy -- South Africa , Technical institutes -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:1326 , http://hdl.handle.net/10962/d1013166
- Description: Knowledge is often tacit and under researched in educational fields. In order for student access to knowledge and its related academic discourses to be facilitated, a deep understanding needs to be gained of the form that this knowledge takes. This study interrogates the ways in which knowledge is constituted in the first year of a Public Management Diploma and a Public Administration Degree at a comprehensive university in South Africa. The study takes a social realist approach that understands reality as fact but sees our knowledge thereof as a social phenomenon. The study was concerned with knowledge structures and knower structures as it argues that these have not been adequately accounted for in the sociology of education research. But this study comes to this concern from a strongly ideological view of student reading and writing. This study calls on a social practices approach that sees literacy as embedded within specific academic discourses, which vary from context to context. It uses this ideological understanding of literacy as the orienting framework for the study of knowledge. The study takes place in a Higher Education mileu that has begun to transform from its divisive past. The transformation brought about new institutional formations such as the comprehensive university, with its mix of vocational, professional and formative programmes and varied emphasis on contextual and conceptual curriculum coherence. Increasingly, the transformation agenda also shifts concern from simply providing physical access to a previously disenfranchised majority to ensuring full participation in the context of high attrition rates in first year and low retention rates. The data was analysed using the Specialisation Codes of Legitimation Code Theory to see what was being specialised in the Diploma and Degree curricula of the Public Management and Administration fields. These fields are characterised in the literature by ongoing tensions about focus, and perceptions of there being a theoretical vacuum and an inability to deal adequately with challenges in the South African public sector. Analysis of lecturer interviews and first-year curriculum documentation showed that both the Public Management Diploma and Public Administration Degree have stronger epistemic relations (ER), with an emphasis on claims to knowledge of the world. The data showed relatively weak social relations (SR), in that there was not the valuing of a particular lens on the world or a specific disposition required for legitimation within this field. The combination of ER+ and SR- indicates that these curricula are Knowledge Codes, where legitimation is through the acquisition of a set of skills and procedures. The programmes were characterised by fairly low-level procedural knowledge, which may point to a workplace-oriented direction that is dominant in the comprehensive university. In keeping with concerns raised in the literature about this field, there was little evidence of theoretical or propositional knowledge in the Public Management Diploma and while the Public Administration Degree had some evidence of this, it was arguably not to the extent expected of a degree as described in the National Qualifications Framework. This study was limited to the first-year of the Diploma and Degree and subsequent years could present different findings. Lecturers showed awareness of student challenges with literacy practices and made concerned attempts through various interventions to address this but they were found to value the surface features of writing practices over personal engagement with the knowledge. Though the expectations of student literacy practices in tests and assignments were aligned to the ways in which knowledge was constructed in the curriculum, there was little evidence of student induction into disciplinary discourses of the field as knowledge was presented as being neutral and student writing primarily took the form of retelling objective facts. The implications of these findings could include student exclusion from higher-level academic discourse, more powerful knowledge in the workplace and, finally, constrain them from becoming producers of knowledge.
- Full Text:
- Date Issued: 2014
Faecal source tracking and water quality in the Eastern Cape, South Africa
- Authors: Luyt, Catherine Diane
- Date: 2013
- Subjects: Water quality -- South Africa -- Grahamstown , Waterborne infection -- Management , Drinking water -- Contamination -- South Africa -- Grahamstown
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:6052 , http://hdl.handle.net/10962/d1018242
- Description: Water quality is concerning as many still lack access to safe drinking water. Alternate sources such as rivers (FC up to 1600 CFUs/100 mL) and rainwater are often polluted. Rainwater tanks require maintenance to improve water quality, but could be used for non-potable purposes or irrigation. Grahamstown infrastructural failures initiate deviations from DWAF 1996 domestic water guidelines for microorganisms within the distribution system. Frequent testing can decrease risks of waterborne diseases. Limitations to this are inaccessibility of rural areas, distances from testing centres and costs. The low cost H2S strip test able to be used onsite by communities, may aid in risk assessment. H2S strip test results are not affected by sulphate (14 to 4240 mg/L) or nitrite (up to 47 mg/L). Transportation of the H2S strip tests between 10 and 32°C does not modify results significantly. Similarly to other studies: Klebsiella spp.; Enterobacter spp. and Serratia spp. were isolated from H2S strip tests. The mH2S strip test corresponds best with HPC in treated water, while in untreated river water it has approximately 90% correspondence with FCs, while survival of FC causes discrepancies with the H2S test after 22 days. A faecal coliform inactivation rate of 0.1 CFUs/ day, may be longer than many pathogens. Faecal source tracking, not currently practised in South Africa, could aid health risk assessments for disaster management, which would improve the NMMP programme. Bacterial survival times could propose the time period for which water is unsafe. Bifidobacteria and Rhodococcus are proposed to help identify the faecal pollution source. But enumeration of Rhodococcus is too lengthy (21 days). The tracking ratio of bifidobacteria (between 0.1 to 6.25) is not source definitive. The bifidobacteria survival rate, could indicator the time since faecal pollution. The bifidobacteria average survival rate is 2.3 CFUs per day for both groups. The culturability and selectivity of agar is still poor, with total bifidobacteria less selectively culturable. Enterococci overgrowth of TB was decreased by Beerens media. SUB is still useful to identify potential human faecal inputs. A single tracking method is thus not suitable alone, but requires a combination of techniques.
- Full Text:
- Date Issued: 2013
- Authors: Luyt, Catherine Diane
- Date: 2013
- Subjects: Water quality -- South Africa -- Grahamstown , Waterborne infection -- Management , Drinking water -- Contamination -- South Africa -- Grahamstown
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:6052 , http://hdl.handle.net/10962/d1018242
- Description: Water quality is concerning as many still lack access to safe drinking water. Alternate sources such as rivers (FC up to 1600 CFUs/100 mL) and rainwater are often polluted. Rainwater tanks require maintenance to improve water quality, but could be used for non-potable purposes or irrigation. Grahamstown infrastructural failures initiate deviations from DWAF 1996 domestic water guidelines for microorganisms within the distribution system. Frequent testing can decrease risks of waterborne diseases. Limitations to this are inaccessibility of rural areas, distances from testing centres and costs. The low cost H2S strip test able to be used onsite by communities, may aid in risk assessment. H2S strip test results are not affected by sulphate (14 to 4240 mg/L) or nitrite (up to 47 mg/L). Transportation of the H2S strip tests between 10 and 32°C does not modify results significantly. Similarly to other studies: Klebsiella spp.; Enterobacter spp. and Serratia spp. were isolated from H2S strip tests. The mH2S strip test corresponds best with HPC in treated water, while in untreated river water it has approximately 90% correspondence with FCs, while survival of FC causes discrepancies with the H2S test after 22 days. A faecal coliform inactivation rate of 0.1 CFUs/ day, may be longer than many pathogens. Faecal source tracking, not currently practised in South Africa, could aid health risk assessments for disaster management, which would improve the NMMP programme. Bacterial survival times could propose the time period for which water is unsafe. Bifidobacteria and Rhodococcus are proposed to help identify the faecal pollution source. But enumeration of Rhodococcus is too lengthy (21 days). The tracking ratio of bifidobacteria (between 0.1 to 6.25) is not source definitive. The bifidobacteria survival rate, could indicator the time since faecal pollution. The bifidobacteria average survival rate is 2.3 CFUs per day for both groups. The culturability and selectivity of agar is still poor, with total bifidobacteria less selectively culturable. Enterococci overgrowth of TB was decreased by Beerens media. SUB is still useful to identify potential human faecal inputs. A single tracking method is thus not suitable alone, but requires a combination of techniques.
- Full Text:
- Date Issued: 2013
An investigation of Grade 11 Oshindonga teachers' understanding and implementation of the learner-centered approach adopted in Namibia : a case study
- Mbangula, Christofina Nalweendo
- Authors: Mbangula, Christofina Nalweendo
- Date: 2011
- Subjects: Student-centered learning -- Namibia Ndonga language -- Study and teaching -- Namibia Teachers -- Training of -- Namibia Educational change -- Namibia Education -- Namibia
- Language: English
- Type: Thesis , Masters , MEd
- Identifier: vital:1628 , http://hdl.handle.net/10962/d1003510
- Description: Before the Republic of Namibia achieved independence in 1990, Bantu Education was the prevailing structure used to promote the social, economic, and political ethos of apartheid through a teacher-centered education system. After 1990, Namibia underwent a major restructuring of education. Learner-centered education was introduced as an inclusive and participatory approach to achieve the reform goals. One of the aims was to review the existing Language policy and to promote mother tongue teaching, since it is through language we internalize our experience and construct our own understanding. In other words, our cognitive, emotional and social development is dependent on language. In this case study, the understanding and implementation of a learner-centered approach in Namibia were investigated in order to gain insights about how the participating education officer, responsible for Oshindonga understands and assists teachers to implement this approach. At the same time, this study aimed at investigating Grade 11 teachers‟ understanding and implementation of LCE in their classrooms. The qualitative methodology in this case study used semi-structured interviews, classroom observations and document analysis for data collection. The data revealed that there are a number of misconceptions. In some cases, what teachers say is not what they do. The findings suggest that teachers, while attempting to implement a learner-centered approach, are not confident about its underlying theory, and therefore the degree of implementation depends on how the teachers used their understanding of that theory in their practice within these conceptual constraints. The study highlights particular challenges and problems that hinder the effective implementation of learner-centered education.
- Full Text:
- Date Issued: 2011
- Authors: Mbangula, Christofina Nalweendo
- Date: 2011
- Subjects: Student-centered learning -- Namibia Ndonga language -- Study and teaching -- Namibia Teachers -- Training of -- Namibia Educational change -- Namibia Education -- Namibia
- Language: English
- Type: Thesis , Masters , MEd
- Identifier: vital:1628 , http://hdl.handle.net/10962/d1003510
- Description: Before the Republic of Namibia achieved independence in 1990, Bantu Education was the prevailing structure used to promote the social, economic, and political ethos of apartheid through a teacher-centered education system. After 1990, Namibia underwent a major restructuring of education. Learner-centered education was introduced as an inclusive and participatory approach to achieve the reform goals. One of the aims was to review the existing Language policy and to promote mother tongue teaching, since it is through language we internalize our experience and construct our own understanding. In other words, our cognitive, emotional and social development is dependent on language. In this case study, the understanding and implementation of a learner-centered approach in Namibia were investigated in order to gain insights about how the participating education officer, responsible for Oshindonga understands and assists teachers to implement this approach. At the same time, this study aimed at investigating Grade 11 teachers‟ understanding and implementation of LCE in their classrooms. The qualitative methodology in this case study used semi-structured interviews, classroom observations and document analysis for data collection. The data revealed that there are a number of misconceptions. In some cases, what teachers say is not what they do. The findings suggest that teachers, while attempting to implement a learner-centered approach, are not confident about its underlying theory, and therefore the degree of implementation depends on how the teachers used their understanding of that theory in their practice within these conceptual constraints. The study highlights particular challenges and problems that hinder the effective implementation of learner-centered education.
- Full Text:
- Date Issued: 2011
Intellectualisation of African languages with particular reference to isiXhosa
- Authors: Maseko, Pamela
- Date: 2011
- Subjects: Xhosa language -- Study and teaching -- South Africa , Language and education -- South Africa , African languages
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/58035 , vital:27035
- Description: The research explores the relationship between language and education, and motivates for the intellectualisation of African languages, isiXhosa in particular, and for their use in education. The main rationale behind this is that access to, and success in education can largely be realised if that education is mediated in one’s first language. The thesis discusses works of prominent scholars who have written on the subject - relating cognitive abilities and achievement in education to language in which that education is offered. The lack of terminology in new domains in African languages as barrier to mother tongue education is laid bare by looking specifically at the history of intellectualisation of isiXhosa, from the missionaries in the 1820s up to the new endeavours as recently as 2008. Terminologies that were developed during the Bantu Education era, where development of isiXhosa and other indigenous African languages was accelerated in order to respond to the demands of moedertaal-onderwys (mother tongue education) are surveyed, and the process of their development analysed. Three main terminology lists developed during this period are analysed against terminology development principles, approaches and methods that are seen as a measure to ensure quality terminology development. The efforts of the development of isiXhosa during the post-apartheid South Africa, especially the government-driven initiatives, are also critiqued even though these are not as effective and as extensive, especially in education. The result of this analysis is that African languages and isiXhosa in particular, can be used in scientific disciplines and at the highest levels of education. Its grammar is advanced, and its lexicon is extensive such that new concepts that need to be named can be named, using appropriate term creation strategies. There are also technological tools such as WordSmith tools that can be used that can advance its development, ensuring that the concept represented in the newly-created term is precise, concise and appropriate in terms of its discipline. Therefore it is argued that, in the interim, terminologies should be developed, in various subjects, to support learning, which at this stage is mediated in English, for those students who have other languages as mother tongue. Those terminologies that have been developed in the various historical periods should be collated, revised and brought into the classrooms. The thesis argues that real intellectualisation of isiXhosa and other African languages rests on the use of these languages in classrooms and lecture halls, and in the value that all role players place on these languages.
- Full Text:
- Date Issued: 2011
- Authors: Maseko, Pamela
- Date: 2011
- Subjects: Xhosa language -- Study and teaching -- South Africa , Language and education -- South Africa , African languages
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/58035 , vital:27035
- Description: The research explores the relationship between language and education, and motivates for the intellectualisation of African languages, isiXhosa in particular, and for their use in education. The main rationale behind this is that access to, and success in education can largely be realised if that education is mediated in one’s first language. The thesis discusses works of prominent scholars who have written on the subject - relating cognitive abilities and achievement in education to language in which that education is offered. The lack of terminology in new domains in African languages as barrier to mother tongue education is laid bare by looking specifically at the history of intellectualisation of isiXhosa, from the missionaries in the 1820s up to the new endeavours as recently as 2008. Terminologies that were developed during the Bantu Education era, where development of isiXhosa and other indigenous African languages was accelerated in order to respond to the demands of moedertaal-onderwys (mother tongue education) are surveyed, and the process of their development analysed. Three main terminology lists developed during this period are analysed against terminology development principles, approaches and methods that are seen as a measure to ensure quality terminology development. The efforts of the development of isiXhosa during the post-apartheid South Africa, especially the government-driven initiatives, are also critiqued even though these are not as effective and as extensive, especially in education. The result of this analysis is that African languages and isiXhosa in particular, can be used in scientific disciplines and at the highest levels of education. Its grammar is advanced, and its lexicon is extensive such that new concepts that need to be named can be named, using appropriate term creation strategies. There are also technological tools such as WordSmith tools that can be used that can advance its development, ensuring that the concept represented in the newly-created term is precise, concise and appropriate in terms of its discipline. Therefore it is argued that, in the interim, terminologies should be developed, in various subjects, to support learning, which at this stage is mediated in English, for those students who have other languages as mother tongue. Those terminologies that have been developed in the various historical periods should be collated, revised and brought into the classrooms. The thesis argues that real intellectualisation of isiXhosa and other African languages rests on the use of these languages in classrooms and lecture halls, and in the value that all role players place on these languages.
- Full Text:
- Date Issued: 2011
Studies in marine quinone chemistry
- Authors: Sunassee, Suthananda Naidu
- Date: 2011
- Subjects: Quinone Marine natural products Marine invertebrates Marine pharmacology Cancer -- Treatment
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4355 , http://hdl.handle.net/10962/d1005020
- Description: This thesis is divided into two parts and the rationale of the research conducted is based on the cytotoxicity of the prenylated quinones 1.24-1.29, isolated from the South African nudibranch Leminda millecra, against oesophageal cancer cells. The first part (Chapters 2 and 3) of the thesis initially documents the distribution of cytotoxic and antioxidant prenylated quinones and hydroquinones in the marine environment. We have been able to show, for the first time, that these compounds can be divided into eight structural classes closely related to their phyletic distribution. Secondly, we attempted to synthesize the two marine natural products 1.24 and 1.26 in an effort to contribute to an ongoing collaborative search with the Division of Medical Biochemistry at the University of Cape Town for new compounds with anti-oesophageal cancer activity. Accordingly, we followed the published synthetic procedure for 1.26 and, although we were unable to reproduce the reported results, we have generated five new prenylated quinone analogues 3.53-3.55, 3.63 and 3.71, which are a potentially viable addition to our ongoing structure-activity relationship (SAR) studies. Moreover, we embarked on a 7Li NMR mechanistic study for the synthesis of 3.2 from 3.1 which rewarded us with an improved and reproducible methodology for this crucial reaction that is detailed in Chapter 3. The second part of this thesis (Chapters 4 and 5) is concerned with a synthetic, structural, electrochemical and biological exploration of the 1,4-naphthoquinone nucleus as a primary pharmacophore in our search for new chemical entities which can induce apoptosis in oesophageal cancer cells, thus contributing to our overall ongoing SAR study in this class of compounds. Seven new naphthoquinone derivatves (4.19, 4.30, 4.31, 4.33 and 4.46-4.48) of the natural products 2-deoxylapachol (2.44), lapachol (4.1) and β-lapachone (5.2) were synthesized and 2-(1`-hydroxy-`-phenylmethyl)-1,4-naphthoquinone (4.29) was found to be the most cytotoxic (IC50 1.5 μM) against the oesophageal cancer cell line WHCO1, while 5.2, which is currently in phase II clinical trials as an anticancer drug, was found to be similarly active (IC50 1.6 μM). Electrochemical investigations of the redox properties of the benzylic alcohol derivatives 4.29-4.31 indicated a higher reduction potential compared to their oxidized counterparts 4.45-4.48, and this finding has been correlated to the increased activity of 4.29-4.31 against the WHCO1 cell line. Additionally, 4.29 is synthetically more accessible than either 1.26 or 5.2 and potentially a lead compound in our search for new and more effective chemotherapeutic agents against oesophageal cancer
- Full Text:
- Date Issued: 2011
- Authors: Sunassee, Suthananda Naidu
- Date: 2011
- Subjects: Quinone Marine natural products Marine invertebrates Marine pharmacology Cancer -- Treatment
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4355 , http://hdl.handle.net/10962/d1005020
- Description: This thesis is divided into two parts and the rationale of the research conducted is based on the cytotoxicity of the prenylated quinones 1.24-1.29, isolated from the South African nudibranch Leminda millecra, against oesophageal cancer cells. The first part (Chapters 2 and 3) of the thesis initially documents the distribution of cytotoxic and antioxidant prenylated quinones and hydroquinones in the marine environment. We have been able to show, for the first time, that these compounds can be divided into eight structural classes closely related to their phyletic distribution. Secondly, we attempted to synthesize the two marine natural products 1.24 and 1.26 in an effort to contribute to an ongoing collaborative search with the Division of Medical Biochemistry at the University of Cape Town for new compounds with anti-oesophageal cancer activity. Accordingly, we followed the published synthetic procedure for 1.26 and, although we were unable to reproduce the reported results, we have generated five new prenylated quinone analogues 3.53-3.55, 3.63 and 3.71, which are a potentially viable addition to our ongoing structure-activity relationship (SAR) studies. Moreover, we embarked on a 7Li NMR mechanistic study for the synthesis of 3.2 from 3.1 which rewarded us with an improved and reproducible methodology for this crucial reaction that is detailed in Chapter 3. The second part of this thesis (Chapters 4 and 5) is concerned with a synthetic, structural, electrochemical and biological exploration of the 1,4-naphthoquinone nucleus as a primary pharmacophore in our search for new chemical entities which can induce apoptosis in oesophageal cancer cells, thus contributing to our overall ongoing SAR study in this class of compounds. Seven new naphthoquinone derivatves (4.19, 4.30, 4.31, 4.33 and 4.46-4.48) of the natural products 2-deoxylapachol (2.44), lapachol (4.1) and β-lapachone (5.2) were synthesized and 2-(1`-hydroxy-`-phenylmethyl)-1,4-naphthoquinone (4.29) was found to be the most cytotoxic (IC50 1.5 μM) against the oesophageal cancer cell line WHCO1, while 5.2, which is currently in phase II clinical trials as an anticancer drug, was found to be similarly active (IC50 1.6 μM). Electrochemical investigations of the redox properties of the benzylic alcohol derivatives 4.29-4.31 indicated a higher reduction potential compared to their oxidized counterparts 4.45-4.48, and this finding has been correlated to the increased activity of 4.29-4.31 against the WHCO1 cell line. Additionally, 4.29 is synthetically more accessible than either 1.26 or 5.2 and potentially a lead compound in our search for new and more effective chemotherapeutic agents against oesophageal cancer
- Full Text:
- Date Issued: 2011
A study of the biopharmaceutics and pharmacokinetics of the macrolide antibiotic, erythromycin
- Authors: Terespolsky, Susan Ann
- Date: 1992
- Subjects: Erythromycin -- Bioavailability , Erythromycin -- Pharmacokinetics
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3795 , http://hdl.handle.net/10962/d1003273 , Erythromycin -- Bioavailability , Erythromycin -- Pharmacokinetics
- Description: Erythromycin, a macrolide antibiotic isolated from Streptomyces erythreus, was first introduced into clinical medicine in 1952. It is active against most gram-positive bacteria, some gram-negative bacteria and is currently the agent of choice for Legionella pneumophila. Erythromycin is an acid-labile compound rapidly degrading in acidic solutions such as the acid environment of the stomach. As such, erythromycin absorption following oral administration of solid dosage forms is relatively poor. Accordingly there have been various approaches used to protect the drug against gastric inactivation. These precautions include enteric-coating of tablets, capsules or pellets of erythromycin base, the synthesis of acid stable 2' esters of erythromycin (ethylsuccinate and propionate) and salts of these esters (erythromycin estolate), and more recently, the synthesis of a range of new acid-stable, semi-synthetic macrolide antibiotics. The 2' esters are antimicrobially inactive or much less active than the parent compound and must be converted to the free erythromycin base in vivo in order to exhibit antibacterial activity. Intrinsic dissolution rates determined on raw material can provide extremely useful information relating to the gastrointestinal absorption of drugs from solid dosage forms. The large inter- and intrasubject variability associated with erythromycin base has, to date, mainly been attributed to gastric acid inactivation of the drug. However, changes in duodenal pH resulting in altered solubility and intrinsic dissolution rates may account for the observed variability. Thus, the intrinsic dissolution rates of erythromycin base at pH 6.0, 6.5, 7.0, 7.5 and 8.0 were compared in order to investigate the possible effects of pH changes which may occur in the duodenal contents, on the in vivo dissolution and subsequent absorption of this compound. The standard intrinsic dissolution rate test procedure employing a rotating disc of pure erythromycin base powder which only allows for dissolution from a constant surface area, was adapted and the drug quantitatively determined by reversed phase high performance liquid chromatography (HPLC) using ultraviolet detection. Results of intrinsic dissolution studies at both 22°C and 37°C indicate that the solubility, and therefore the rate of dissolution of erythromycin base is pH dependent, being more soluble at pH 6.0 than pH 8.0 (an approximate 800 times and 1000 times reduction in the amount dissolved after 30 minutes, at 22°C and 37°C respectively, when the pH of the medium was increased from 6 to 8). Although the stability of erythromycin and its ester derivatives in aqueous acidic solutions has been well documented, very little has been reported on the compound's stability in organic solvents. Methanol is recommended by official drug compendia (U.S.P. and B.P.) for use in erythromycin identification tests as well as in the sample preparation steps during assay procedures. Thus, the effect of methanol and acetonitrile, organic solvents of similar polarities and densities, on the stability of erythromycin base, erythromycin ethylsuccinate, propionyl erythromycin and erythromycin estolate at room temperature (22°C ± 0.5°C), using HPLC with electrochemical detection, was investigated. Erythromycin base is relatively stable in both methanol and acetonitrile, remaining intact for over 168 hours in acetonitrile and showing less than 5% degradation in methanol over the same period. Erythromycin ethylsuccinate in acetonitrile shows less than 5% degradation over 168 hours whereas in methanol, rapid hydrolysis occurs resulting in almost total conversion to base within 40 hours. Approximately 87% of erythromycin propionyl ester remained intact after 168 hours in acetonitrile whilst methanol caused rapid hydrolysis to erythromycin base (35% remaining after 28 hours). Erythromycin estolate appeared to be unstable in both acetonitrile and methanol. In acetonitrile, only 13% of the estolate remained intact after 168 hours, whereas in methanol, the reaction was much more rapid with 35% of the estolate remaining after 28 hours. The use of methanol as a solvent for erythromycin estolate reference standards is thus contraindicated. A number of conflicting reports on the half- life as well as the body compartment model that best describes erythromycin base serum concentration-time profiles (lBCM generally used to describe orally administered erythromycin, whilst a 2BCM has been used to describe erythromycin administered intravenously), appear in the literature. These differences may be largely attributed to the sampling period (between 6 and 12 hours) used in the repective studies. The objective of this study was to determine the body compartment model that best describes erythromycin base serum concentration-time curves by increasing the sampling time to 24 hours. In addition, the effect of chronic dosing of erythromycin on erythromycin pharmacokinetics, in the same group of subjects, was investigated. The single and multiple oral dose pharmacokinetics of erythromycin enteric coated base pellets within a gelatin capsule (250mg), were studied in 6 healthy, normal volunteers (19.5 ± 0.76 years, 71.5 ± 8.18 kg, 180.33 ± 5.99 cm). Furthermore, steady state concentrations were predicted using the pharmacokinetic parameters obtained from the single dose study, and compared with those obtained in the multiple dose study. Plasma concentrations were determined using a sensitive high-performance liquid chromatographic method with electrochemical detection. For the single dose study, after a tlag of 2.5 ± 0.71 hr, Cmax (1.12 ± 0.47 μ/ml) was reached at a tmax of 4.08 ± 0.93 hr post dose, with serum concentrations ranging from 0.31 - 1.62 μ/ml. The half-life was found to be 5.42 ± 1.31 hr. On multiple dosing (250mg six hourly), serum concentrations for the fifth, ninth and thirteenth dosing intervals ranged from 0.67 - 2.92 μ/ml, 1.69 - 3.65 μ/ml and 0.61 - 3.01 μ/ml, occurring at 3.75 ± 0.69 hr, 3.17 ± 1.03 hr and 3.17 ± 1.03 hr post dose with a Cmax of 1.89 ± 0.68 μ/ml, 2.35 ± 0.70 μ/ml and 1.94 ± 0.74 μ/ml, respectively. The area under the serum concentration- time curve for the single dose study (AUC₀₋∞) was 4.67 ± 0.88 hr.μ/ml, whilst the AUC₀₋τ. for the fifth, ninth and thirteenth dosing intervals of the multiple dose study were 5.77 ± 1.76 hr.μ/ml, 6.46 ± 1.33 hr.μ/ml and 5.97 ± 2.36 hr.μ/ml respectively, indicating an approximately 33% increase in AUC on chronic dosing of erythromycin. The observed increase in AUC may be a result of increased bioavailability or a decrease in clearance on chronic dosing.
- Full Text: false
- Date Issued: 1992
- Authors: Terespolsky, Susan Ann
- Date: 1992
- Subjects: Erythromycin -- Bioavailability , Erythromycin -- Pharmacokinetics
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3795 , http://hdl.handle.net/10962/d1003273 , Erythromycin -- Bioavailability , Erythromycin -- Pharmacokinetics
- Description: Erythromycin, a macrolide antibiotic isolated from Streptomyces erythreus, was first introduced into clinical medicine in 1952. It is active against most gram-positive bacteria, some gram-negative bacteria and is currently the agent of choice for Legionella pneumophila. Erythromycin is an acid-labile compound rapidly degrading in acidic solutions such as the acid environment of the stomach. As such, erythromycin absorption following oral administration of solid dosage forms is relatively poor. Accordingly there have been various approaches used to protect the drug against gastric inactivation. These precautions include enteric-coating of tablets, capsules or pellets of erythromycin base, the synthesis of acid stable 2' esters of erythromycin (ethylsuccinate and propionate) and salts of these esters (erythromycin estolate), and more recently, the synthesis of a range of new acid-stable, semi-synthetic macrolide antibiotics. The 2' esters are antimicrobially inactive or much less active than the parent compound and must be converted to the free erythromycin base in vivo in order to exhibit antibacterial activity. Intrinsic dissolution rates determined on raw material can provide extremely useful information relating to the gastrointestinal absorption of drugs from solid dosage forms. The large inter- and intrasubject variability associated with erythromycin base has, to date, mainly been attributed to gastric acid inactivation of the drug. However, changes in duodenal pH resulting in altered solubility and intrinsic dissolution rates may account for the observed variability. Thus, the intrinsic dissolution rates of erythromycin base at pH 6.0, 6.5, 7.0, 7.5 and 8.0 were compared in order to investigate the possible effects of pH changes which may occur in the duodenal contents, on the in vivo dissolution and subsequent absorption of this compound. The standard intrinsic dissolution rate test procedure employing a rotating disc of pure erythromycin base powder which only allows for dissolution from a constant surface area, was adapted and the drug quantitatively determined by reversed phase high performance liquid chromatography (HPLC) using ultraviolet detection. Results of intrinsic dissolution studies at both 22°C and 37°C indicate that the solubility, and therefore the rate of dissolution of erythromycin base is pH dependent, being more soluble at pH 6.0 than pH 8.0 (an approximate 800 times and 1000 times reduction in the amount dissolved after 30 minutes, at 22°C and 37°C respectively, when the pH of the medium was increased from 6 to 8). Although the stability of erythromycin and its ester derivatives in aqueous acidic solutions has been well documented, very little has been reported on the compound's stability in organic solvents. Methanol is recommended by official drug compendia (U.S.P. and B.P.) for use in erythromycin identification tests as well as in the sample preparation steps during assay procedures. Thus, the effect of methanol and acetonitrile, organic solvents of similar polarities and densities, on the stability of erythromycin base, erythromycin ethylsuccinate, propionyl erythromycin and erythromycin estolate at room temperature (22°C ± 0.5°C), using HPLC with electrochemical detection, was investigated. Erythromycin base is relatively stable in both methanol and acetonitrile, remaining intact for over 168 hours in acetonitrile and showing less than 5% degradation in methanol over the same period. Erythromycin ethylsuccinate in acetonitrile shows less than 5% degradation over 168 hours whereas in methanol, rapid hydrolysis occurs resulting in almost total conversion to base within 40 hours. Approximately 87% of erythromycin propionyl ester remained intact after 168 hours in acetonitrile whilst methanol caused rapid hydrolysis to erythromycin base (35% remaining after 28 hours). Erythromycin estolate appeared to be unstable in both acetonitrile and methanol. In acetonitrile, only 13% of the estolate remained intact after 168 hours, whereas in methanol, the reaction was much more rapid with 35% of the estolate remaining after 28 hours. The use of methanol as a solvent for erythromycin estolate reference standards is thus contraindicated. A number of conflicting reports on the half- life as well as the body compartment model that best describes erythromycin base serum concentration-time profiles (lBCM generally used to describe orally administered erythromycin, whilst a 2BCM has been used to describe erythromycin administered intravenously), appear in the literature. These differences may be largely attributed to the sampling period (between 6 and 12 hours) used in the repective studies. The objective of this study was to determine the body compartment model that best describes erythromycin base serum concentration-time curves by increasing the sampling time to 24 hours. In addition, the effect of chronic dosing of erythromycin on erythromycin pharmacokinetics, in the same group of subjects, was investigated. The single and multiple oral dose pharmacokinetics of erythromycin enteric coated base pellets within a gelatin capsule (250mg), were studied in 6 healthy, normal volunteers (19.5 ± 0.76 years, 71.5 ± 8.18 kg, 180.33 ± 5.99 cm). Furthermore, steady state concentrations were predicted using the pharmacokinetic parameters obtained from the single dose study, and compared with those obtained in the multiple dose study. Plasma concentrations were determined using a sensitive high-performance liquid chromatographic method with electrochemical detection. For the single dose study, after a tlag of 2.5 ± 0.71 hr, Cmax (1.12 ± 0.47 μ/ml) was reached at a tmax of 4.08 ± 0.93 hr post dose, with serum concentrations ranging from 0.31 - 1.62 μ/ml. The half-life was found to be 5.42 ± 1.31 hr. On multiple dosing (250mg six hourly), serum concentrations for the fifth, ninth and thirteenth dosing intervals ranged from 0.67 - 2.92 μ/ml, 1.69 - 3.65 μ/ml and 0.61 - 3.01 μ/ml, occurring at 3.75 ± 0.69 hr, 3.17 ± 1.03 hr and 3.17 ± 1.03 hr post dose with a Cmax of 1.89 ± 0.68 μ/ml, 2.35 ± 0.70 μ/ml and 1.94 ± 0.74 μ/ml, respectively. The area under the serum concentration- time curve for the single dose study (AUC₀₋∞) was 4.67 ± 0.88 hr.μ/ml, whilst the AUC₀₋τ. for the fifth, ninth and thirteenth dosing intervals of the multiple dose study were 5.77 ± 1.76 hr.μ/ml, 6.46 ± 1.33 hr.μ/ml and 5.97 ± 2.36 hr.μ/ml respectively, indicating an approximately 33% increase in AUC on chronic dosing of erythromycin. The observed increase in AUC may be a result of increased bioavailability or a decrease in clearance on chronic dosing.
- Full Text: false
- Date Issued: 1992
Between freedom and givenness: (a study of the hermeneutical consequences of the concept of canon for the authority of scripture)
- Authors: Latham, Jonathan Cyril
- Date: 1990
- Subjects: Bible -- Evidences, authority, etc. , Authority -- Religious aspects , Canon (Literature
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:1216 , http://hdl.handle.net/10962/d1001546
- Description: The aim of this thesis is to arrive at an understanding of the authority of scripture that is able to accommodate both a faith perspective and the fruits of the historical-critical approach to the New Testament. Put differently, the aim of this thesis is the pursuit of a specifically christian, faith-promoting, reading of the New Testament whilst still enjoying the benefit, in an as uncompromised a form as possible, of the historical- critical approach. In a sense it may be said that this task, given that the roots of both the historical-critical approach and modern Western culture are deeply imbedded in Rationalism, is equivalent to the basic hermeneutical question of whether it is possible to interpret scripture relevantly from within a cultural web of meaning that does not readily accommodate that embodied in the New Testament. In section one of this dissertation we present a characteristic depiction, based on the historical-critical theory of literature, of the authority of the New Testament. This is followed by a brief assessment that makes explicit why the historical- critical approach is not conducive to the adoption of a faith perspective on these writings. In section two, still and inevitably based on critical foundations, we adopt a perspective that is more sympathetic to faith and that seeks to discover in the concerns evidenced in the canonical process, when traditions about Jesus gradually took on more complex and stable forms, culminating in the canon of the New Testament, guidelines in helping us to deal with the problem with which this study is concerned . In the specific example of the rather ordinary concerns underlying the unusual history of the pericope de adultera (John 7:53-8:11), examined against the background of the interests underlying the canonical process, it becomes clear that christians from the very beginning faced a dilemma not unlike that with which the historical-critical approach confronts us. They had to interpret afresh, and faithfully, the traditions in order to meet the demands of situations that had never been foreseen by earlier tradents. In this respect, therefore, the history of the pericope de adultera presents us with an ongoing struggle to hold in tension the demands of new contexts with the imperative of strict continuity with Jesus. In section three, on the basis of the foundation of the authority of scripture in strict continuity with Jesus combined with the contextual reinterpretation of the tradition, the social sciences are employed. Using the social sciences, it is discovered that the two contradictory approaches that we wish to reconcile form part of two different models for interpreting reality. It is on this basis, and made possible by the common culture underlying these opposing models and by the common contact with an unspecified common core of concrete reality, that a solution is proposed in terms of a complex 'fusion of horizons', promoted by a 'precipitative environment'. In the conclusion our solution is decisively aligned with the concerns evidenced in the canonical process
- Full Text:
- Date Issued: 1990
- Authors: Latham, Jonathan Cyril
- Date: 1990
- Subjects: Bible -- Evidences, authority, etc. , Authority -- Religious aspects , Canon (Literature
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:1216 , http://hdl.handle.net/10962/d1001546
- Description: The aim of this thesis is to arrive at an understanding of the authority of scripture that is able to accommodate both a faith perspective and the fruits of the historical-critical approach to the New Testament. Put differently, the aim of this thesis is the pursuit of a specifically christian, faith-promoting, reading of the New Testament whilst still enjoying the benefit, in an as uncompromised a form as possible, of the historical- critical approach. In a sense it may be said that this task, given that the roots of both the historical-critical approach and modern Western culture are deeply imbedded in Rationalism, is equivalent to the basic hermeneutical question of whether it is possible to interpret scripture relevantly from within a cultural web of meaning that does not readily accommodate that embodied in the New Testament. In section one of this dissertation we present a characteristic depiction, based on the historical-critical theory of literature, of the authority of the New Testament. This is followed by a brief assessment that makes explicit why the historical- critical approach is not conducive to the adoption of a faith perspective on these writings. In section two, still and inevitably based on critical foundations, we adopt a perspective that is more sympathetic to faith and that seeks to discover in the concerns evidenced in the canonical process, when traditions about Jesus gradually took on more complex and stable forms, culminating in the canon of the New Testament, guidelines in helping us to deal with the problem with which this study is concerned . In the specific example of the rather ordinary concerns underlying the unusual history of the pericope de adultera (John 7:53-8:11), examined against the background of the interests underlying the canonical process, it becomes clear that christians from the very beginning faced a dilemma not unlike that with which the historical-critical approach confronts us. They had to interpret afresh, and faithfully, the traditions in order to meet the demands of situations that had never been foreseen by earlier tradents. In this respect, therefore, the history of the pericope de adultera presents us with an ongoing struggle to hold in tension the demands of new contexts with the imperative of strict continuity with Jesus. In section three, on the basis of the foundation of the authority of scripture in strict continuity with Jesus combined with the contextual reinterpretation of the tradition, the social sciences are employed. Using the social sciences, it is discovered that the two contradictory approaches that we wish to reconcile form part of two different models for interpreting reality. It is on this basis, and made possible by the common culture underlying these opposing models and by the common contact with an unspecified common core of concrete reality, that a solution is proposed in terms of a complex 'fusion of horizons', promoted by a 'precipitative environment'. In the conclusion our solution is decisively aligned with the concerns evidenced in the canonical process
- Full Text:
- Date Issued: 1990
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