Use of a non-hepatic cell line highlights limitations associated with cell-based assessment of metabolically induced toxicity:
- Weyers, Carli, Dingle, Laura M K, Wilhelmi, Brendan S, Edkins, Adrienne L, Veale, Clinton G
- Authors: Weyers, Carli , Dingle, Laura M K , Wilhelmi, Brendan S , Edkins, Adrienne L , Veale, Clinton G
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/160290 , vital:40431 , DOI: 10.1080/01480545.2019.1585869
- Description: Metabolically induced drug-toxicity is a major cause of drug failure late in drug optimization phases. Accordingly, in vitro metabolic profiling of compounds is being introduced at earlier stages of the drug discovery pipeline. An increasingly common method to obtain these profiles is through overexpression of key CYP450 metabolic enzymes in immortalized liver cells, to generate competent hepatocyte surrogates. Enhanced cytotoxicity is presumed to be due to toxic metabolite production via the overexpressed enzyme. However, metabolically induced toxicity is a complex multi-parameter phenomenon and the potential background contribution to metabolism arising from the use of liver cells which endogenously express CYP450 isoforms is consistently overlooked. In this study, we sought to reduce the potential background interference by applying this methodology in kidney-derived HEK293 cells which lack endogenous CYP450 expression.
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- Date Issued: 2020
- Authors: Weyers, Carli , Dingle, Laura M K , Wilhelmi, Brendan S , Edkins, Adrienne L , Veale, Clinton G
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/160290 , vital:40431 , DOI: 10.1080/01480545.2019.1585869
- Description: Metabolically induced drug-toxicity is a major cause of drug failure late in drug optimization phases. Accordingly, in vitro metabolic profiling of compounds is being introduced at earlier stages of the drug discovery pipeline. An increasingly common method to obtain these profiles is through overexpression of key CYP450 metabolic enzymes in immortalized liver cells, to generate competent hepatocyte surrogates. Enhanced cytotoxicity is presumed to be due to toxic metabolite production via the overexpressed enzyme. However, metabolically induced toxicity is a complex multi-parameter phenomenon and the potential background contribution to metabolism arising from the use of liver cells which endogenously express CYP450 isoforms is consistently overlooked. In this study, we sought to reduce the potential background interference by applying this methodology in kidney-derived HEK293 cells which lack endogenous CYP450 expression.
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- Date Issued: 2020
An (auto)-biographical account of nursing transformation: 1970-2018
- Authors: Ricks, Esmeralda Jennifer
- Subjects: Nursing -- Study and teaching , Nursing -- South Africa
- Language: English
- Type: text , An (auto)-biographical account of nursing transformation: 1970-2018 , Lectures
- Identifier: http://hdl.handle.net/10948/21055 , vital:29434
- Description: This lecture provides a description of how nursing education and practice, research and technology has transformed over the past 48 years. The information provided in this lecture is based on personal experience and own research, and research of various other authors. The first part of the lecture provides an overview of the era in which I trained and is used as a benchmark to compare current day practices. The changes in nursing education and practice with regard to the Nursing Act and regulations over the past 48 years are highlighted, depicting the number of times that the different nursing acts and regulations were amended with regard to all basic nursing qualification programmes. This lecture also includes a brief discussion of the new nursing education programme that will be implemented soon, as well as its opportunities and challenges. A detailed description is provided with regard to how nursing research has evolved over the past 48 years because of the dedication and vision that nurse leaders have for the profession. A national nursing strategy has been developed to enhance collaborative, rigorous scientific enquiry that builds a significant body of knowledge in order to improve the health of the people of South Africa. It is envisaged that the research strategy will contribute significantly to directing future nursing research development in South Africa. It is evident in this lecture that the use of technology in nursing has truly evolved and can be seen as a major driver of changes in the nursing profession. There are huge shifts in how patient records are maintained, how medications are tracked and ordered, how care is passed from one provider to another, how blood and X-ray results are retrieved and how information is being accessed at the point of care in nursing. In today’s healthcare system technology is the foundation of the future. Today’s nurses must not only know how to care for patients, but how to use technology safely and appropriately in their day-to-day work. It is evident that nursing has transformed in many ways since 1970 and that nurses have always been the drivers of nursing transformation.
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- Authors: Ricks, Esmeralda Jennifer
- Subjects: Nursing -- Study and teaching , Nursing -- South Africa
- Language: English
- Type: text , An (auto)-biographical account of nursing transformation: 1970-2018 , Lectures
- Identifier: http://hdl.handle.net/10948/21055 , vital:29434
- Description: This lecture provides a description of how nursing education and practice, research and technology has transformed over the past 48 years. The information provided in this lecture is based on personal experience and own research, and research of various other authors. The first part of the lecture provides an overview of the era in which I trained and is used as a benchmark to compare current day practices. The changes in nursing education and practice with regard to the Nursing Act and regulations over the past 48 years are highlighted, depicting the number of times that the different nursing acts and regulations were amended with regard to all basic nursing qualification programmes. This lecture also includes a brief discussion of the new nursing education programme that will be implemented soon, as well as its opportunities and challenges. A detailed description is provided with regard to how nursing research has evolved over the past 48 years because of the dedication and vision that nurse leaders have for the profession. A national nursing strategy has been developed to enhance collaborative, rigorous scientific enquiry that builds a significant body of knowledge in order to improve the health of the people of South Africa. It is envisaged that the research strategy will contribute significantly to directing future nursing research development in South Africa. It is evident in this lecture that the use of technology in nursing has truly evolved and can be seen as a major driver of changes in the nursing profession. There are huge shifts in how patient records are maintained, how medications are tracked and ordered, how care is passed from one provider to another, how blood and X-ray results are retrieved and how information is being accessed at the point of care in nursing. In today’s healthcare system technology is the foundation of the future. Today’s nurses must not only know how to care for patients, but how to use technology safely and appropriately in their day-to-day work. It is evident that nursing has transformed in many ways since 1970 and that nurses have always been the drivers of nursing transformation.
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Arsenic in the boardroom: strategies to deal with toxic leaders
- Authors: Mey, Michelle
- Subjects: Bullying in the workplace , Psychology, Industrial
- Language: English
- Type: text , Lectures
- Identifier: http://hdl.handle.net/10948/20945 , vital:29421
- Description: Effective leaders are critical in building successful organisations, communities and nations. Whilst academia and business alike advocate positive organisational psychology and the development of positive leadership, the sad reality is that there is a growing global prevalence of toxic leadership, with research indicating that between 20% and 60% of leaders may be defined as toxic (Veldsman, 2016). While toxic leaders, who initially come across as charming, confident and persuasive, may be effective in achieving organisational objectives in the short term, the long-term consequences can be devastating to the organisational brand and reputation, as well as to the morale and psyche of its members. Even though toxic leaders and bullies are becoming increasingly prevalent in organisations there is a lack of empirical research on workplace bullying.
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- Authors: Mey, Michelle
- Subjects: Bullying in the workplace , Psychology, Industrial
- Language: English
- Type: text , Lectures
- Identifier: http://hdl.handle.net/10948/20945 , vital:29421
- Description: Effective leaders are critical in building successful organisations, communities and nations. Whilst academia and business alike advocate positive organisational psychology and the development of positive leadership, the sad reality is that there is a growing global prevalence of toxic leadership, with research indicating that between 20% and 60% of leaders may be defined as toxic (Veldsman, 2016). While toxic leaders, who initially come across as charming, confident and persuasive, may be effective in achieving organisational objectives in the short term, the long-term consequences can be devastating to the organisational brand and reputation, as well as to the morale and psyche of its members. Even though toxic leaders and bullies are becoming increasingly prevalent in organisations there is a lack of empirical research on workplace bullying.
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Cinnamoyl-Oxaborole Amides: Synthesis and Their in Vitro Biological Activity.
- Gumbo, Maureen, Beteck, Richard M, Mandizvo, Tawanda, Seldon, Ronnett, Warner, Digby F, Hoppe, Heinrich C, Isaacs, Michelle, Laming, Dustin, Tam, Christina C, Cheng, Luisa W, Liu, Nicole, Land, Kirkwood, Khanye, Setshaba D
- Authors: Gumbo, Maureen , Beteck, Richard M , Mandizvo, Tawanda , Seldon, Ronnett , Warner, Digby F , Hoppe, Heinrich C , Isaacs, Michelle , Laming, Dustin , Tam, Christina C , Cheng, Luisa W , Liu, Nicole , Land, Kirkwood , Khanye, Setshaba D
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122879 , vital:35362 , https://doi.org/10.3390/molecules23082038
- Description: Due to the increased interest in their application in the treatment of infectious diseases, boron-containing compounds have received a significant coverage in the literature. Herein, a small set of novel cinnamoly-oxaborole amides were synthesized and screened against nagana Trypanosoma brucei brucei for antitrypanosomal activity. Compound 5g emerged as a new hit with an in vitro IC50 value of 0.086 μM against T. b. brucei without obvious inhibitory activity against HeLa cell lines. The same series was also screened against other human pathogens, including Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), for which moderate to weak activity (10 to >125 μM) was observed. Similarly, these compounds exhibited moderate activity against the human protozoal pathogen Trichomonas vaginalis with no observed effect on common microbiome bacterial species. The cross-species inhibitory activity presents the possibility of these compounds serving as broad-spectrum antibiotics for these prevalent three human pathogens.
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- Authors: Gumbo, Maureen , Beteck, Richard M , Mandizvo, Tawanda , Seldon, Ronnett , Warner, Digby F , Hoppe, Heinrich C , Isaacs, Michelle , Laming, Dustin , Tam, Christina C , Cheng, Luisa W , Liu, Nicole , Land, Kirkwood , Khanye, Setshaba D
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122879 , vital:35362 , https://doi.org/10.3390/molecules23082038
- Description: Due to the increased interest in their application in the treatment of infectious diseases, boron-containing compounds have received a significant coverage in the literature. Herein, a small set of novel cinnamoly-oxaborole amides were synthesized and screened against nagana Trypanosoma brucei brucei for antitrypanosomal activity. Compound 5g emerged as a new hit with an in vitro IC50 value of 0.086 μM against T. b. brucei without obvious inhibitory activity against HeLa cell lines. The same series was also screened against other human pathogens, including Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), for which moderate to weak activity (10 to >125 μM) was observed. Similarly, these compounds exhibited moderate activity against the human protozoal pathogen Trichomonas vaginalis with no observed effect on common microbiome bacterial species. The cross-species inhibitory activity presents the possibility of these compounds serving as broad-spectrum antibiotics for these prevalent three human pathogens.
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Happiness: a business model
- Authors: Cullen, Margaret
- Subjects: Happiness , f-sa
- Language: English
- Type: text , Lectures
- Identifier: http://hdl.handle.net/10948/20956 , vital:29422
- Description: The concept of happiness might appear elusive. It has been extensively analysed by philosophers and historians, who agree that the concept of happiness in antiquity centered on good luck and fortune. Something beyond human agency and therefore controlled by the Gods (McMahon, 2006).Today, happiness is viewed as something over which you can have control and something that can be pursued (Oishi, 2012).
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- Authors: Cullen, Margaret
- Subjects: Happiness , f-sa
- Language: English
- Type: text , Lectures
- Identifier: http://hdl.handle.net/10948/20956 , vital:29422
- Description: The concept of happiness might appear elusive. It has been extensively analysed by philosophers and historians, who agree that the concept of happiness in antiquity centered on good luck and fortune. Something beyond human agency and therefore controlled by the Gods (McMahon, 2006).Today, happiness is viewed as something over which you can have control and something that can be pursued (Oishi, 2012).
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Novobiocin–ferrocene conjugates possessing anticancer and antiplasmodial activity independent of HSP90 inhibition.
- Mbaba, Mziyanda, de la Mare, Jo-Anne, Sterrenberg, Jason N, Kajewole, Deborah, Maharaj, Shantal, Edkins, Adrienne L, Isaacs, Michelle, Hoppe, Heinrich C, Khanye, Setshaba D
- Authors: Mbaba, Mziyanda , de la Mare, Jo-Anne , Sterrenberg, Jason N , Kajewole, Deborah , Maharaj, Shantal , Edkins, Adrienne L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122858 , vital:35359 , https://doi.org/10.1007/s00775-018-1634-9
- Description: A series of tailored novobiocin–ferrocene conjugates was prepared in moderate yields and investigated for in vitro anticancer and antiplasmodial activity against the MDA-MB-231 breast cancer line and Plasmodium falciparum 3D7 strain, respectively. While the target compounds displayed moderate anticancer activity against the breast cancer cell line with IC50 values in the mid-micromolar range, compounds 10a–c displayed promising antiplasmodial activity as low as 0.889 µM. Furthermore, the most promising compounds were tested for inhibitory effects against a postulated target, heat shock protein 90 (Hsp90).
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- Authors: Mbaba, Mziyanda , de la Mare, Jo-Anne , Sterrenberg, Jason N , Kajewole, Deborah , Maharaj, Shantal , Edkins, Adrienne L , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122858 , vital:35359 , https://doi.org/10.1007/s00775-018-1634-9
- Description: A series of tailored novobiocin–ferrocene conjugates was prepared in moderate yields and investigated for in vitro anticancer and antiplasmodial activity against the MDA-MB-231 breast cancer line and Plasmodium falciparum 3D7 strain, respectively. While the target compounds displayed moderate anticancer activity against the breast cancer cell line with IC50 values in the mid-micromolar range, compounds 10a–c displayed promising antiplasmodial activity as low as 0.889 µM. Furthermore, the most promising compounds were tested for inhibitory effects against a postulated target, heat shock protein 90 (Hsp90).
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The Plastic University: Knowledge, Disciplines and Decolonial 'Circulations'
- Authors: Keet, Andre
- Subjects: Critical pedagogy , Transformative learning , f-sa
- Language: English
- Type: text , Lectures
- Identifier: http://hdl.handle.net/10948/21077 , vital:29436
- Description: The university is as plastic as the social figure of ‘Mandela’ after whom it is named. It is as plastic as the globe and its humanity in whose name it exists. And, it is as plastic as the human subject that is ‘perpetually called on to reconfigure itself in relation to the artefacts of the age’, as Mbembe2 argues in Critique of Black Reason. The very nature of addressing, of writing … of inaugurating … oneself, through an address is an act of reconfiguration, of responding to an artefact of the university and the professoriate. It is, when all is said and done, a performance, a performative act: declaring so and so a professor of this or that status, authorizing ‘it’ to utter something with some kind of formative force.
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- Authors: Keet, Andre
- Subjects: Critical pedagogy , Transformative learning , f-sa
- Language: English
- Type: text , Lectures
- Identifier: http://hdl.handle.net/10948/21077 , vital:29436
- Description: The university is as plastic as the social figure of ‘Mandela’ after whom it is named. It is as plastic as the globe and its humanity in whose name it exists. And, it is as plastic as the human subject that is ‘perpetually called on to reconfigure itself in relation to the artefacts of the age’, as Mbembe2 argues in Critique of Black Reason. The very nature of addressing, of writing … of inaugurating … oneself, through an address is an act of reconfiguration, of responding to an artefact of the university and the professoriate. It is, when all is said and done, a performance, a performative act: declaring so and so a professor of this or that status, authorizing ‘it’ to utter something with some kind of formative force.
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