A critical analysis of Professor Andrew Tracey’s contribution to African music pedagogy and the field of applied ethnomusicology
- Authors: Moyo, Vuyelwa O'Lacy
- Date: 2022-10-14
- Subjects: Tracey, Andrew T N , Ethnomusicology , Music Instruction and study Africa , Mbira Zimbabwe
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/406829 , vital:70311
- Description: The research presented in this thesis is based on my interest and experience in forms of African music, ethnomusicology, and studying mbira with Professor Emeritus Andrew Tracey. When I arrived in South Africa in 2019 to join Rhodes University’s Applied Ethnomusicology programme, I chose to study the mbira with Tracey as the idea of learning more about Zimbabwe through music was important to the formation of my identity. Through the lens of embodied learning and a practice-based approach in this research, I evaluate how Tracey’s numerous contributions to African music pedagogy have improved prospects for African music scholars and students in terms of contributing to the goals of applied ethnomusicology. The primary purpose of this thesis is to respond to the absence of serious scrutiny of existing pedagogical approaches to African music at universities across South Africa. The contribution this research makes will be valuable to African music programmes across the continent as well as to practitioners of African traditional instruments, such as the marimba, mbira, timbila xylophones, nyanga pan pipes, and valimba xylophones. The thesis comprises five chapters. The first presents an introduction to the research, and its goals, procedures and approaches, along with an outline of the subsequent chapters. Tracey’s biography is covered in the second chapter. A consideration of the state of African music teaching in other African countries such as Ghana, Kenya, and Zimbabwe; the history of African music; and the state of African music pedagogy in tertiary institutions in South Africa constitutes the third chapter. Chapter 4 comprises an analysis of Tracey’s articles and data gathered from interviews, as well as my personal reflections as Tracey’s student. The final chapter presents a summary of the preceding chapters, the study’s findings, and suggestions for further research. A multidisciplinary approach was used for this thesis. The results finds that Tracey’s articles had six common themes which he wrote about and are a contribution to African music pedagogy. These themes are the history of instruments, the structure of the instrument, the learning/playing technique, structure of the instrument, transcription and dance steps. , Thesis (MMus) -- Faculty of Humanities, Music and Musicology, 2022
- Full Text:
- Authors: Moyo, Vuyelwa O'Lacy
- Date: 2022-10-14
- Subjects: Tracey, Andrew T N , Ethnomusicology , Music Instruction and study Africa , Mbira Zimbabwe
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/406829 , vital:70311
- Description: The research presented in this thesis is based on my interest and experience in forms of African music, ethnomusicology, and studying mbira with Professor Emeritus Andrew Tracey. When I arrived in South Africa in 2019 to join Rhodes University’s Applied Ethnomusicology programme, I chose to study the mbira with Tracey as the idea of learning more about Zimbabwe through music was important to the formation of my identity. Through the lens of embodied learning and a practice-based approach in this research, I evaluate how Tracey’s numerous contributions to African music pedagogy have improved prospects for African music scholars and students in terms of contributing to the goals of applied ethnomusicology. The primary purpose of this thesis is to respond to the absence of serious scrutiny of existing pedagogical approaches to African music at universities across South Africa. The contribution this research makes will be valuable to African music programmes across the continent as well as to practitioners of African traditional instruments, such as the marimba, mbira, timbila xylophones, nyanga pan pipes, and valimba xylophones. The thesis comprises five chapters. The first presents an introduction to the research, and its goals, procedures and approaches, along with an outline of the subsequent chapters. Tracey’s biography is covered in the second chapter. A consideration of the state of African music teaching in other African countries such as Ghana, Kenya, and Zimbabwe; the history of African music; and the state of African music pedagogy in tertiary institutions in South Africa constitutes the third chapter. Chapter 4 comprises an analysis of Tracey’s articles and data gathered from interviews, as well as my personal reflections as Tracey’s student. The final chapter presents a summary of the preceding chapters, the study’s findings, and suggestions for further research. A multidisciplinary approach was used for this thesis. The results finds that Tracey’s articles had six common themes which he wrote about and are a contribution to African music pedagogy. These themes are the history of instruments, the structure of the instrument, the learning/playing technique, structure of the instrument, transcription and dance steps. , Thesis (MMus) -- Faculty of Humanities, Music and Musicology, 2022
- Full Text:
Assessment of cytotoxic artemisinin and its derivatives as DNA damaging inducing agents in triple-negative breast cancer cells
- Authors: Mkhwanazi, Ntando
- Date: 2022-10-14
- Subjects: Breast Cancer , Artemisinin , DNA damage , Antineoplastic agents , Breast Cancer Treatment
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362960 , vital:65378
- Description: In developing countries, including South Africa, breast cancer is the primary cause of cancer-related deaths among women. TNBC (triple-negative breast cancer) is an aggressive breast cancer subtype that is more prevalent in women of African descent. This subtype lacks the key receptors, namely the estrogen receptor (ER-), progesterone receptor (PR-), and human epidermal growth factor receptor 2 (HER2-) that are the basis of successful targeted therapies for other subtypes of the disease. To date, there are no effective, standardized targeted therapies for TNBC. Artemisinin is an anti-malarial drug and numerous derivatives of the compound have been developed to improve the potency and solubility of the parent compound. Artemisinin and its derivatives have gained attention as potential anti-cancer agents; however, such studies have not yet progressed to clinical trials and the precise mechanism of action of these compounds is yet to be fully explained. In this study, artemisinin, and its known derivative artesunate, as well as a novel derivative, WHN11, were investigated as DNA damage-inducing agents in TNBC. WHN11 was found to be the most potent of the three compounds, displaying an IC50 of 3.20 μM against HCC70 cells, artemisinin displayed an IC50 of 214.70 μM and artesunate displayed an IC50 of 25.48 μM. The compounds were less toxic to the MCF12A non-cancerous cells, with IC50 values 298.30, 87.53, and 8.35 μM for artemisinin, artesunate, and WHN11, respectively, and displayed selectivity indices of 1.39, 3.44 and 2.61 μM for artemisinin, artesunate, and WHN11, respectively. In silico and in vitro studies revealed that the artemisinin compounds bind to DNA through the minor groove. While all three compounds were able to bind to DNA, a comet assay revealed that only artemisinin and artesunate, and not WHN11, were able to cause DNA damage compared to the vehicle control, DMSO. Finally, a topoisomerase I (TOPO I) enzyme assay demonstrated that while the compounds appeared to display a degree of inhibition of TOPO I, as evidenced by a downward shift in the plasmid band on the agarose gel, they were not able to fully inhibit the enzyme to return the plasmid to the supercoiled conformation. In addition, combination studies revealed that artemisinin, artesunate, and WHN11 acted synergistically in combination with camptothecin, but displayed either an additive (artemisinin) or antagonistic (artesunate and WHN11) relationship when used in combination with etoposide. In conclusion, artemisinin, its known derivative artesunate, and novel and highly toxic derivative WHN11, all bind to DNA via the minor groove, however only artemisinin and artesunate, and not WHN11, cause DNA damage, indicating a potentially different mechanism of action of the three artemisinins. All three compounds act synergistically with camptothecin, which suggests interference with topoisomerase activity, partially supported by slight inhibition of TOPO I activity, and could indicate either direct inhibition of the enzyme or interference with enzyme function by competitive binding to the DNA. Further studies could help explore alternate DNA damage assays, to validate these findings, and the effect of the compounds on TOPO II activity could also be assessed. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Authors: Mkhwanazi, Ntando
- Date: 2022-10-14
- Subjects: Breast Cancer , Artemisinin , DNA damage , Antineoplastic agents , Breast Cancer Treatment
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362960 , vital:65378
- Description: In developing countries, including South Africa, breast cancer is the primary cause of cancer-related deaths among women. TNBC (triple-negative breast cancer) is an aggressive breast cancer subtype that is more prevalent in women of African descent. This subtype lacks the key receptors, namely the estrogen receptor (ER-), progesterone receptor (PR-), and human epidermal growth factor receptor 2 (HER2-) that are the basis of successful targeted therapies for other subtypes of the disease. To date, there are no effective, standardized targeted therapies for TNBC. Artemisinin is an anti-malarial drug and numerous derivatives of the compound have been developed to improve the potency and solubility of the parent compound. Artemisinin and its derivatives have gained attention as potential anti-cancer agents; however, such studies have not yet progressed to clinical trials and the precise mechanism of action of these compounds is yet to be fully explained. In this study, artemisinin, and its known derivative artesunate, as well as a novel derivative, WHN11, were investigated as DNA damage-inducing agents in TNBC. WHN11 was found to be the most potent of the three compounds, displaying an IC50 of 3.20 μM against HCC70 cells, artemisinin displayed an IC50 of 214.70 μM and artesunate displayed an IC50 of 25.48 μM. The compounds were less toxic to the MCF12A non-cancerous cells, with IC50 values 298.30, 87.53, and 8.35 μM for artemisinin, artesunate, and WHN11, respectively, and displayed selectivity indices of 1.39, 3.44 and 2.61 μM for artemisinin, artesunate, and WHN11, respectively. In silico and in vitro studies revealed that the artemisinin compounds bind to DNA through the minor groove. While all three compounds were able to bind to DNA, a comet assay revealed that only artemisinin and artesunate, and not WHN11, were able to cause DNA damage compared to the vehicle control, DMSO. Finally, a topoisomerase I (TOPO I) enzyme assay demonstrated that while the compounds appeared to display a degree of inhibition of TOPO I, as evidenced by a downward shift in the plasmid band on the agarose gel, they were not able to fully inhibit the enzyme to return the plasmid to the supercoiled conformation. In addition, combination studies revealed that artemisinin, artesunate, and WHN11 acted synergistically in combination with camptothecin, but displayed either an additive (artemisinin) or antagonistic (artesunate and WHN11) relationship when used in combination with etoposide. In conclusion, artemisinin, its known derivative artesunate, and novel and highly toxic derivative WHN11, all bind to DNA via the minor groove, however only artemisinin and artesunate, and not WHN11, cause DNA damage, indicating a potentially different mechanism of action of the three artemisinins. All three compounds act synergistically with camptothecin, which suggests interference with topoisomerase activity, partially supported by slight inhibition of TOPO I activity, and could indicate either direct inhibition of the enzyme or interference with enzyme function by competitive binding to the DNA. Further studies could help explore alternate DNA damage assays, to validate these findings, and the effect of the compounds on TOPO II activity could also be assessed. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2022
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Conceptualising mental distress from an African psychology paradigm: using an interpretative phenomenological analysis of the views of traditional healers
- Nabo-Bazana, Sandisiwe Sifanelwe
- Authors: Nabo-Bazana, Sandisiwe Sifanelwe
- Date: 2022-10-14
- Subjects: Healers South Africa , Traditional healer , Mental distress , Black psychology , Afrocentrism
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/406213 , vital:70249
- Description: With South Africa's long history of colonialism and racial oppression, there are still services in the country that many South Africans cannot relate to, including psychology. Research shows that many South Africans experience and are affected by mental distress due to several factors, including poverty, unemployment, and traumatic experiences. Managing and treating such distress has always been challenging for most South Africans. Some debates question the relevance of psychological services from the West in a South African context. This study explores other approaches to psychology that look beyond the Biopsychosocial model when dealing with certain types of disorders in an African context. African psychology, or the Afrocentric approach, looks at what is beneath the surface, not just the presenting problem. Mainstream psychology strives to be universal and applicable to all. However, African psychology disagrees with this notion. African psychology perceives human beings as strongly influenced by social and cultural influences. The focus of this approach includes the spiritual realm and the attached meanings. There is evidence for the need to merge Traditional and Western medicine. The research methodology for this study is qualitative, using Interpretative Phenomenological Analysis. IPA allows for a critical engagement with the ways in which participants construct their reality. The researcher carried out semi-structured interviews to enable participants, all traditional healers (3 female and 2 male), to narrate their experiences dealing with mentally distressed clients. The accounts of these traditional healers were analysed focusing on people who have experienced mental distress. From the analysis and synthesis of the themes, findings illustrate how traditional healers conceptualise and construct mental distress from an African Psychology paradigm. An emerging core theme was the importance of the divine call and its influence on the chosen treatments. More studies are needed to illustrate the potential for collaboration between African Traditional healing and EuroAmerican healing practices, to provide holistic services to people in need. , Thesis (MA) -- Faculty of Humanities, Psychology, 2022
- Full Text:
- Authors: Nabo-Bazana, Sandisiwe Sifanelwe
- Date: 2022-10-14
- Subjects: Healers South Africa , Traditional healer , Mental distress , Black psychology , Afrocentrism
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/406213 , vital:70249
- Description: With South Africa's long history of colonialism and racial oppression, there are still services in the country that many South Africans cannot relate to, including psychology. Research shows that many South Africans experience and are affected by mental distress due to several factors, including poverty, unemployment, and traumatic experiences. Managing and treating such distress has always been challenging for most South Africans. Some debates question the relevance of psychological services from the West in a South African context. This study explores other approaches to psychology that look beyond the Biopsychosocial model when dealing with certain types of disorders in an African context. African psychology, or the Afrocentric approach, looks at what is beneath the surface, not just the presenting problem. Mainstream psychology strives to be universal and applicable to all. However, African psychology disagrees with this notion. African psychology perceives human beings as strongly influenced by social and cultural influences. The focus of this approach includes the spiritual realm and the attached meanings. There is evidence for the need to merge Traditional and Western medicine. The research methodology for this study is qualitative, using Interpretative Phenomenological Analysis. IPA allows for a critical engagement with the ways in which participants construct their reality. The researcher carried out semi-structured interviews to enable participants, all traditional healers (3 female and 2 male), to narrate their experiences dealing with mentally distressed clients. The accounts of these traditional healers were analysed focusing on people who have experienced mental distress. From the analysis and synthesis of the themes, findings illustrate how traditional healers conceptualise and construct mental distress from an African Psychology paradigm. An emerging core theme was the importance of the divine call and its influence on the chosen treatments. More studies are needed to illustrate the potential for collaboration between African Traditional healing and EuroAmerican healing practices, to provide holistic services to people in need. , Thesis (MA) -- Faculty of Humanities, Psychology, 2022
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Development and optimisation of a qPCR assay for the enumeration of Cryptophlebia leucotreta granulovirus (CrleGV) used for commercial applications
- Authors: Mela, Thuthula
- Date: 2022-10-14
- Subjects: Cryptophlebia leucotreta granulovirus , Cryptophlebia leucotreta , Late expression factor 8 (LEF-8) , Late expression factor 9 , Dark field microscopy , Genomic DNA , Polymerase chain reaction , Plasmids
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362949 , vital:65377
- Description: The citrus industry contributes significantly to the South African agricultural sector. Thaumatotibia leucotreta (Meyrick) (Lepidoptera: Tortricidae) is highly important to the South African citrus industry as it is classified as a phytosanitary pest by most international markets. Thaumatotibia leucotreta has caused an estimated annual loss of up to R100 million to the industry. In order to control T. leucotreta in South Africa, an integrated pest management (IPM) programme has been used. One of the components of this programme is Cryptophlebia leucotreta granulovirus (CrleGV), which has been formulated to a registered biopesticide namely Cryptogran and has been successfully applied in the field for over 15 years. To use CrleGV as biopesticides, quantification of the viral particles is required to perform bioassays for field trials and formulation, among other applications. Darkfield microscopy is a traditional method used for the quantification of CrleGV; however, the method is characterised as being subjective, tedious, labour intensive, and time-consuming. This study aims to develop and optimise a qPCR technique to accurately quantify CrleGV-SA OBs using plasmid DNA for downstream applications. Firstly, lef-8, lef-9, and granulin conserved genes from CrleGV-SA and CrleGV-CV3 genome sequences were analysed by performing multiple alignments to evaluate the degree of identity between these genes. This was done to design two sets of oligonucleotides (internal and external) from regions with the highest identity. Subsequently, in silico testing was done to evaluate the designed oligonucleotides to determine whether they specifically bind to the selected target regions. Secondly, three sets of DNA plasmids (pJET1.2-Gran, pJET1.2-lef-9, and pJET1.2-lef-8) were constructed, each containing a target region for either granulin, lef-9, and lef-8 genes for use as standards in a downstream qPCR assay. This was achieved by first extracting gDNA from CrleGV-SA OBs and using the gDNA as a template to PCR amplify the target regions of the selected gene regions with the designed oligonucleotides. Subsequently, the PCR amplified regions were then directly ligated into the pJET1.2/blunt vector, and the plasmids were confirmed by colony PCR, restriction enzyme digestion, and Sanger sequencing. Thirdly, two different methods of CrleGV-SA gDNA extraction were compared to determine which method has the best yields in terms of concentration. The extraction methods compared were the Quick-DNA Miniprep Plus kit according to manufacturer’s instructions (Method 1a), pre-treatment with Na2CO3 prior to using the Quick-DNA Miniprep Plus kit (Method 1b), pre- treatment with Na2CO3, and neutralisation with Tris-HCl prior to gDNA extraction using the Quick-DNA Miniprep Plus kit (Method 1c) and the CTAB method (Method 2). The gDNA concentration and purity for all samples were determined using a Nanodrop spectrophotometer. Method 1c (Na2CO3 and Tris-HCl pre-treated plus Quick-DNA Miniprep Plus kit) was the most efficient at extracting genomic DNA compared with the other methods, resulting in the highest DNA concentration in short processing time. Fourthly, plasmid standards were evaluated for use in the qPCR assay. This was done as it was important to consider the efficacy of the oligonucleotides; including the ability of the oligonucleotides to anneal to the appropriate segment of DNA without extensive formation of oligonucleotides dimers, non-specific annealing, or formation of secondary structure. In addition, it was done to ensure that highly accurate standard curves were generated. The standard curves were to be utilised in the downstream qPCR assay to determine the quantity of test samples by interpolation, reading from the values within the standard curve. Lastly, darkfield microscopy and qPCR methods of enumeration were compared to verify their accuracy and determine the most consistent and comparable method. This was achieved by quantifying the purified, crude-purified, and viral formulated CrleGV-SA suspensions using these methods. Subsequently, a statistical analysis was conducted to compare the results produced by the two enumeration methods. The obtained results showed that the granulin, lef- 8 and lef-9 qPCR values did not significantly differ from the darkfield microscopy results. The findings of this study revealed that the two assays, lef-8 qPCR and lef-9 qPCR, were more robust, sensitive, and efficient for the quantification of CrleGV-SA. Thus, this study has successfully developed a qPCR assay that is comparable with the traditional darkfield microscopy counting technique. This is the first study to use the qPCR technique to enumerate CrleGV-SA using plasmid standards. The developed qPCR assay is reliable, rapid, and cost- effective and has a great potential to be used as an alternative method to darkfield microscopy in the laboratory and commercial settings. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Authors: Mela, Thuthula
- Date: 2022-10-14
- Subjects: Cryptophlebia leucotreta granulovirus , Cryptophlebia leucotreta , Late expression factor 8 (LEF-8) , Late expression factor 9 , Dark field microscopy , Genomic DNA , Polymerase chain reaction , Plasmids
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362949 , vital:65377
- Description: The citrus industry contributes significantly to the South African agricultural sector. Thaumatotibia leucotreta (Meyrick) (Lepidoptera: Tortricidae) is highly important to the South African citrus industry as it is classified as a phytosanitary pest by most international markets. Thaumatotibia leucotreta has caused an estimated annual loss of up to R100 million to the industry. In order to control T. leucotreta in South Africa, an integrated pest management (IPM) programme has been used. One of the components of this programme is Cryptophlebia leucotreta granulovirus (CrleGV), which has been formulated to a registered biopesticide namely Cryptogran and has been successfully applied in the field for over 15 years. To use CrleGV as biopesticides, quantification of the viral particles is required to perform bioassays for field trials and formulation, among other applications. Darkfield microscopy is a traditional method used for the quantification of CrleGV; however, the method is characterised as being subjective, tedious, labour intensive, and time-consuming. This study aims to develop and optimise a qPCR technique to accurately quantify CrleGV-SA OBs using plasmid DNA for downstream applications. Firstly, lef-8, lef-9, and granulin conserved genes from CrleGV-SA and CrleGV-CV3 genome sequences were analysed by performing multiple alignments to evaluate the degree of identity between these genes. This was done to design two sets of oligonucleotides (internal and external) from regions with the highest identity. Subsequently, in silico testing was done to evaluate the designed oligonucleotides to determine whether they specifically bind to the selected target regions. Secondly, three sets of DNA plasmids (pJET1.2-Gran, pJET1.2-lef-9, and pJET1.2-lef-8) were constructed, each containing a target region for either granulin, lef-9, and lef-8 genes for use as standards in a downstream qPCR assay. This was achieved by first extracting gDNA from CrleGV-SA OBs and using the gDNA as a template to PCR amplify the target regions of the selected gene regions with the designed oligonucleotides. Subsequently, the PCR amplified regions were then directly ligated into the pJET1.2/blunt vector, and the plasmids were confirmed by colony PCR, restriction enzyme digestion, and Sanger sequencing. Thirdly, two different methods of CrleGV-SA gDNA extraction were compared to determine which method has the best yields in terms of concentration. The extraction methods compared were the Quick-DNA Miniprep Plus kit according to manufacturer’s instructions (Method 1a), pre-treatment with Na2CO3 prior to using the Quick-DNA Miniprep Plus kit (Method 1b), pre- treatment with Na2CO3, and neutralisation with Tris-HCl prior to gDNA extraction using the Quick-DNA Miniprep Plus kit (Method 1c) and the CTAB method (Method 2). The gDNA concentration and purity for all samples were determined using a Nanodrop spectrophotometer. Method 1c (Na2CO3 and Tris-HCl pre-treated plus Quick-DNA Miniprep Plus kit) was the most efficient at extracting genomic DNA compared with the other methods, resulting in the highest DNA concentration in short processing time. Fourthly, plasmid standards were evaluated for use in the qPCR assay. This was done as it was important to consider the efficacy of the oligonucleotides; including the ability of the oligonucleotides to anneal to the appropriate segment of DNA without extensive formation of oligonucleotides dimers, non-specific annealing, or formation of secondary structure. In addition, it was done to ensure that highly accurate standard curves were generated. The standard curves were to be utilised in the downstream qPCR assay to determine the quantity of test samples by interpolation, reading from the values within the standard curve. Lastly, darkfield microscopy and qPCR methods of enumeration were compared to verify their accuracy and determine the most consistent and comparable method. This was achieved by quantifying the purified, crude-purified, and viral formulated CrleGV-SA suspensions using these methods. Subsequently, a statistical analysis was conducted to compare the results produced by the two enumeration methods. The obtained results showed that the granulin, lef- 8 and lef-9 qPCR values did not significantly differ from the darkfield microscopy results. The findings of this study revealed that the two assays, lef-8 qPCR and lef-9 qPCR, were more robust, sensitive, and efficient for the quantification of CrleGV-SA. Thus, this study has successfully developed a qPCR assay that is comparable with the traditional darkfield microscopy counting technique. This is the first study to use the qPCR technique to enumerate CrleGV-SA using plasmid standards. The developed qPCR assay is reliable, rapid, and cost- effective and has a great potential to be used as an alternative method to darkfield microscopy in the laboratory and commercial settings. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
In vitro pharmacological screening of thiazolidinedione-derivatives on diabetes and Alzheimer’s potential therapeutic targets
- Authors: Arineitwe, Charles
- Date: 2022-10-14
- Subjects: Diabetes Treatment , Alzheimer's disease Treatment , Antioxidants Therapeutic use , Rosiglitazone , Hypoglycemic agents , In vitro screening , Thiazolidinedione Derivatives
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/232171 , vital:49968
- Description: There is an increased prevalence of diabetes and other non-communicable diseases in Sub-Saharan Africa and globally. In South Africa, the prevalence of type 2 Diabetes mellitus is currently estimated at 9.0% in people aged 30 and older and is expected to increase. Diabetes-related complications result in acute alterations in the mental state due to poor metabolic control as well as greater rates of decline in cognitive functioning with age, higher prevalence of depression and increased risk of Alzheimer’s disease. Alzheimer’s disease is the most common form of dementia in older adults and possibly contributes to 60 - 70% of cases. Alzheimer’s disease remains incurable, its progression inevitable with the currently available symptomatic therapies being palliative while the treatment of diabetes relies on insulin preparations and other glucose-lowering agents. Current treatment options have numerous side effects such as hypoglycaemia, diarrhoea, weight gain and abnormal liver function. This has geared the investigation of new generations of small molecules which exhibit improved efficacy and safety profiles. On this basis, several studies have shown that thiazolidinediones and their corresponding derivatives exhibit a broad spectrum of biological activities including anti-inflammatory, and antioxidant activities. Furthermore, recent evidence from experimental, epidemiological, and clinical studies highlight the utility of antioxidants for treating diabetes and its complications. Interestingly, there is increasing evidence that links diabetes and Alzheimer’s disease due to their pathophysiology and suppressing glycaemia has been shown to be beneficial in Alzheimer’s disease treatment. Accordingly, the aim of this study, was to evaluate the anti-diabetic and anti-Alzheimer’s properties of four novel synthesized thiazolidinedione-derivatives owing to their antioxidant properties. Methods The aim of this study was achieved through performing ferric reducing antioxidant power activity, 2,2’-Diphenyl-1-Picry Hydrazyl radical scavenging activity, α-amylase inhibition, α-glucosidase inhibition, aldose reductase inhibition, protein tyrosine phosphatase-1B inhibition, dipeptidyl peptidase-4 inhibition, acetylcholinesterase inhibition, matrix metalloproteinase-1 inhibition, and β-amyloid aggregation inhibition assays. In addition, peroxisome proliferator-activated receptor-γ activation was performed through docking studies. To establish physicochemical properties of TZD derivatives investigated, further in-silico studies were done using SwissADME tools. Results To this end, in-vitro and in-silico studies were successfully performed. In-silico ADME profiling predicted these derivatives to be drug-like with moderate to good solubility in the GI and not blood-brain barrier permeable. Furthermore, docking of these molecules against PPARγ predicted a similar mode of action to that of thiazolidinediones using Rosiglitazone as the standard drug with TZDD2 and TZDD4 forming equivalent conformations to that of Rosiglitazone in the same binding site and TZDD3 having an equivalent LBE to that of Rosiglitazone (-8.84 and -8.63kcal/mol respectively). In-vitro evaluation predicted a moderate antioxidant activity with TZDD2 and 3 exhibiting the highest FRAP activity and DPPH radical scavenging activity. Furthermore, enzymatic inhibition assays showed a relative inhibition activity with TZDD3 exhibited > 100% inhibition in concentrations ≥ 30 μg/mL and TZDD1, 2 and 4 exhibited ≥ 50% inhibition activity in all the concentrations (10, 20, 30, 40 and 50 μg/mL) in the α-amylase inhibition assay. Similarly, in the α-glucosidase inhibition assay, all the four derivatives exhibited a concentration dependent activity with TZDD3 showing the most activity. All the four derivatives exhibited ≥ 30% inhibition in the aldose reductase inhibition assay except TZDD1 at 10 μg/mL. TZDD4 exhibited a concentration dependent inhibition activity in the protein tyrosine phosphatase-1B inhibition assay. Interestingly, TZDD3 showed a decreasing inhibition activity as its concentration increased from 10 μg/mL through to 50 μg/mL. In the dipeptidyl peptidase–4 inhibition assay, TZDD2 and TZDD4 exhibited ≥ 20% inhibition activity across all the concentrations and in the acetylcholinesterase assay, TZDD1, 3 and 4 exhibited ≥ 25% across all the concentrations. Interestingly, in the matrix metalloproteinase-1 inhibition assay, some of these derivatives exhibited partial activation activity and partial inhibition with TZDD1 showing activation in concentrations 10 and 20 μg/mL and inhibition in concentrations 30, 40 and 50 μg/mL. TZDD4 showed activation in all the concentrations. In the β-amyloid aggregation assay, all the four derivatives showed inhibition activity ≥ 10% except TZDD1 at 50 μg/mL. Conclusions Diabetes mellitus and Alzheimer’s disease are a type of pathology of global concern, and several researchers worldwide have strived to search for novel therapeutic treatments and prevention for diabetes as well as Alzheimer’s disease. Recent studies provide a direct link v between diabetes mellitus and Alzheimer’s disease, and the need to find novel drugs that can mitigate these two is of increasing interest. In our search for antidiabetic and anti-Alzheimer’s activity, TZD derivatives (TZDD1, TZDD2, TZDD3 and TZDD4) exhibited good antioxidant activity, anti-hyperglycaemic activity and a relatively promising anti-Alzheimer’s activity. This was observed from the in vitro evaluation performed which included α – amylase, α – glucosidase, aldose reductase, PTP1B, DPP4, amyloid β aggregation, and AChE inhibition assays. Furthermore, docking of the derivatives against PPARγ predicted a similar molecular interaction to that of thiazolidinediones using Rosiglitazone as the standard drug. Furthermore, in silico ADME profiling predicted the derivatives to have moderate to good solubility in the GI (good GI bioavailability), and also exhibited excellent drug likeness. However, they are predicted not permeate the BBB. Further in silico studies and in vivo should be conducted to establish toxicities, as well as drug delivery to the brain for effective therapeutic effect against Alzheimer’s disease. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacology, 2022
- Full Text: false
- Authors: Arineitwe, Charles
- Date: 2022-10-14
- Subjects: Diabetes Treatment , Alzheimer's disease Treatment , Antioxidants Therapeutic use , Rosiglitazone , Hypoglycemic agents , In vitro screening , Thiazolidinedione Derivatives
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/232171 , vital:49968
- Description: There is an increased prevalence of diabetes and other non-communicable diseases in Sub-Saharan Africa and globally. In South Africa, the prevalence of type 2 Diabetes mellitus is currently estimated at 9.0% in people aged 30 and older and is expected to increase. Diabetes-related complications result in acute alterations in the mental state due to poor metabolic control as well as greater rates of decline in cognitive functioning with age, higher prevalence of depression and increased risk of Alzheimer’s disease. Alzheimer’s disease is the most common form of dementia in older adults and possibly contributes to 60 - 70% of cases. Alzheimer’s disease remains incurable, its progression inevitable with the currently available symptomatic therapies being palliative while the treatment of diabetes relies on insulin preparations and other glucose-lowering agents. Current treatment options have numerous side effects such as hypoglycaemia, diarrhoea, weight gain and abnormal liver function. This has geared the investigation of new generations of small molecules which exhibit improved efficacy and safety profiles. On this basis, several studies have shown that thiazolidinediones and their corresponding derivatives exhibit a broad spectrum of biological activities including anti-inflammatory, and antioxidant activities. Furthermore, recent evidence from experimental, epidemiological, and clinical studies highlight the utility of antioxidants for treating diabetes and its complications. Interestingly, there is increasing evidence that links diabetes and Alzheimer’s disease due to their pathophysiology and suppressing glycaemia has been shown to be beneficial in Alzheimer’s disease treatment. Accordingly, the aim of this study, was to evaluate the anti-diabetic and anti-Alzheimer’s properties of four novel synthesized thiazolidinedione-derivatives owing to their antioxidant properties. Methods The aim of this study was achieved through performing ferric reducing antioxidant power activity, 2,2’-Diphenyl-1-Picry Hydrazyl radical scavenging activity, α-amylase inhibition, α-glucosidase inhibition, aldose reductase inhibition, protein tyrosine phosphatase-1B inhibition, dipeptidyl peptidase-4 inhibition, acetylcholinesterase inhibition, matrix metalloproteinase-1 inhibition, and β-amyloid aggregation inhibition assays. In addition, peroxisome proliferator-activated receptor-γ activation was performed through docking studies. To establish physicochemical properties of TZD derivatives investigated, further in-silico studies were done using SwissADME tools. Results To this end, in-vitro and in-silico studies were successfully performed. In-silico ADME profiling predicted these derivatives to be drug-like with moderate to good solubility in the GI and not blood-brain barrier permeable. Furthermore, docking of these molecules against PPARγ predicted a similar mode of action to that of thiazolidinediones using Rosiglitazone as the standard drug with TZDD2 and TZDD4 forming equivalent conformations to that of Rosiglitazone in the same binding site and TZDD3 having an equivalent LBE to that of Rosiglitazone (-8.84 and -8.63kcal/mol respectively). In-vitro evaluation predicted a moderate antioxidant activity with TZDD2 and 3 exhibiting the highest FRAP activity and DPPH radical scavenging activity. Furthermore, enzymatic inhibition assays showed a relative inhibition activity with TZDD3 exhibited > 100% inhibition in concentrations ≥ 30 μg/mL and TZDD1, 2 and 4 exhibited ≥ 50% inhibition activity in all the concentrations (10, 20, 30, 40 and 50 μg/mL) in the α-amylase inhibition assay. Similarly, in the α-glucosidase inhibition assay, all the four derivatives exhibited a concentration dependent activity with TZDD3 showing the most activity. All the four derivatives exhibited ≥ 30% inhibition in the aldose reductase inhibition assay except TZDD1 at 10 μg/mL. TZDD4 exhibited a concentration dependent inhibition activity in the protein tyrosine phosphatase-1B inhibition assay. Interestingly, TZDD3 showed a decreasing inhibition activity as its concentration increased from 10 μg/mL through to 50 μg/mL. In the dipeptidyl peptidase–4 inhibition assay, TZDD2 and TZDD4 exhibited ≥ 20% inhibition activity across all the concentrations and in the acetylcholinesterase assay, TZDD1, 3 and 4 exhibited ≥ 25% across all the concentrations. Interestingly, in the matrix metalloproteinase-1 inhibition assay, some of these derivatives exhibited partial activation activity and partial inhibition with TZDD1 showing activation in concentrations 10 and 20 μg/mL and inhibition in concentrations 30, 40 and 50 μg/mL. TZDD4 showed activation in all the concentrations. In the β-amyloid aggregation assay, all the four derivatives showed inhibition activity ≥ 10% except TZDD1 at 50 μg/mL. Conclusions Diabetes mellitus and Alzheimer’s disease are a type of pathology of global concern, and several researchers worldwide have strived to search for novel therapeutic treatments and prevention for diabetes as well as Alzheimer’s disease. Recent studies provide a direct link v between diabetes mellitus and Alzheimer’s disease, and the need to find novel drugs that can mitigate these two is of increasing interest. In our search for antidiabetic and anti-Alzheimer’s activity, TZD derivatives (TZDD1, TZDD2, TZDD3 and TZDD4) exhibited good antioxidant activity, anti-hyperglycaemic activity and a relatively promising anti-Alzheimer’s activity. This was observed from the in vitro evaluation performed which included α – amylase, α – glucosidase, aldose reductase, PTP1B, DPP4, amyloid β aggregation, and AChE inhibition assays. Furthermore, docking of the derivatives against PPARγ predicted a similar molecular interaction to that of thiazolidinediones using Rosiglitazone as the standard drug. Furthermore, in silico ADME profiling predicted the derivatives to have moderate to good solubility in the GI (good GI bioavailability), and also exhibited excellent drug likeness. However, they are predicted not permeate the BBB. Further in silico studies and in vivo should be conducted to establish toxicities, as well as drug delivery to the brain for effective therapeutic effect against Alzheimer’s disease. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacology, 2022
- Full Text: false
Linking Hop and LANA1 in the KSHV life cycle
- Authors: Ruck, Jamie-Lee
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/365291 , vital:65724
- Description: Thesis embargoed. Possible release date set for early 2025. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
- Authors: Ruck, Jamie-Lee
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/365291 , vital:65724
- Description: Thesis embargoed. Possible release date set for early 2025. , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2022
- Full Text:
The development, formulation and characterization of an optimized metronidazole loaded solid lipid nanoparticle formulation for ocular drug delivery
- Authors: Sikhondze, Simise Siphelele
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/403014 , vital:69914
- Description: Thesis embargoed. To be released early 2026. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2023
- Full Text:
- Authors: Sikhondze, Simise Siphelele
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/403014 , vital:69914
- Description: Thesis embargoed. To be released early 2026. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2023
- Full Text:
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