List of Titles

Examining the effects of small molecule tyrosine kinase inhibitors on glucose metabolism in skeletal muscle and liver cell lines in vitro

- Mugiya, Takudzwa Cleophas

Authors: Mugiya, Takudzwa Cleophas
Date: 2025-04-02
Subjects: Diabetes , Blood glucose , Cancer , Insulin , Protein kinase B , Glucose transporters
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/478829 , vital:78227
Description: Diabetes mellitus is rising due to aging, sedentary lifestyles, obesity, and unhealthy diets, posing a global health threat. Due to increase in prevalence together with shortfalls associated with current treatment options, there is still a necessity for a continuous search of new pharmacotherapies. Small molecule tyrosine kinase inhibitors are drugs, used in cancer chemotherapy and have been shown to affect glycaemic control and metabolism variably. Studies have shown that tyrosine kinase inhibitors can alter glycaemic control and glucose metabolism, with some demonstrating hypoglycaemic activities whilst others showing hyperglycaemic properties. The mechanism by which tyrosine kinase inhibitors cause glycaemic dysregulation is not well understood, therefore, the clinical significance of these chemotherapeutic agents on glucose handling is also poorly documented. Aims and objectives: This study aims to elucidate how small molecule tyrosine kinase inhibitors affect glucose metabolism in C2C12 and HepG2 cells in vitro, including their impact on glucose uptake, AKT, GLUT-4, and IL-6 expression, GLUT-4 translocation, and alpha-amylase and alpha-glucosidase activity. Methods: In this study, C2C12 and HepG2 cells were seeded in well plates and the initial media glucose concentration was recorded. Cells were then treated with small molecule tyrosine kinase inhibitors; imatinib, dasatinib, axitinib, and erlotinib for 24 hours. Thereafter, the effect of the test drugs was assessed on cell viability, glucose uptake, expression of AKT GLUT-4 and IL-6, and translocation of GLUT-4. Furthermore, effects of the drugs were assessed on the activities of alpha amylase and glucosidase using calometric assays. Results and Discussion: Cells treated with small molecule tyrosine kinase inhibitors were viable after 24 hours. A concentration-dependent increase in glucose uptake in C2C12 cells treated with imatinib was observed as the concentration of imatinib increased. Axitinib, dasatinib, and erlotinib demonstrated glucose uptake levels comparable to the control across all concentrations. Small molecule tyrosine kinase inhibitors demonstrated an increase in GLUT4 translocation in the absence of insulin. GLUT4 expression was comparable in cells treated with small molecule tyrosine kinase inhibitors and the control. Small molecule tyrosine kinase inhibitors showed an increase in AKT expression. C2C12 cells treated with small molecule tyrosine kinase inhibitors were observed to have elevated IL-6 expression compared to the control. The HepG2 cells treated with erlotinib and imatinib demonstrated elevated glucose uptake while cells treated with axitinib and dasatinib were observed to have a lower glucose uptake. Treatment with dasatinib led to a decrease in Akt expression as concentration increased. Small molecule tyrosine kinase inhibitors demonstrated inhibition of alpha-amylase, while only dasatinib and axitinib showed inhibition of alpha-glucosidase. Conclusion: The results show that small molecule tyrosine kinase inhibitors impact glucose metabolism in C2C12 and HepG2 cells via their effect on GLUT-4 translocation and expression and AKT expression. Dasatinib showed promising potential with regard to antidiabetic capabilities. Further research is needed to better understand these mechanisms' effects on metabolic homeostasis and inform future therapeutic strategies. , Thesis (MSc (Pharm)) -- Faculty of Pharmacy, Pharmacy, 2025
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Date Issued: 2025-04-02

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An investigation into the impact of geographical location on the phytochemical composition, pharmacological and toxicological activities of Tulbaghia violacea collected from the Eastern Cape and Gauteng Province

- Kader, Tasmeera

Authors: Kader, Tasmeera
Date: 2024-10-11
Subjects: Tulbaghia violacea , Phytochemicals , Alliaceae Geographical distribution , Diabetes , Alzheimer's disease
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/461819 , vital:76242
Description: Introduction: The number of communicable and non-communicable diseases continues to rise and has become more prevalent. While drugs exist to manage and/ or treat majority of the communicable and non-communicable diseases, the rise in disease prevalence puts pressure on researchers to find new drug molecules to treat and manage these ailments. Traditional medicine refers to the knowledge, skills and practices which are based on the beliefs and experiences indigenous to cultures and is used to maintain health. Most of the research into traditional medicine focuses on the medicinal plants used. Medicinal plants are any plants in which one or more of its organs contain substances which are used for therapeutic purposes or for the synthesis of drugs. Tulbaghia violacea is a monocotyledonous genus of herbaceous perennial bulbs which is native to Africa and can be readily found throughout South Africa. It is popular for its antimicrobial, antifungal, anticoagulant, antioxidant and anticancer properties. It has been that ecological factors influence the composition and quantity of phytochemicals present in a plant. Aim of the study: The aim of the study was to investigate the impact of geographical location on the phytochemical composition, pharmacological and toxicological activities of T. violacea collected from the Eastern Cape and Gauteng Province. Methods: The leaves of T. violacea were collected from the Eastern Cape and Gauteng Province. The leaves were dried and extracted using serial maceration with solvents hexane, acetone and methanol. The resulting extracts were subjected to qualitative preliminary phytochemical analysis and a quantitative total phenol content test was carried out using gallic acid as the standard. Thin layer chromatography (TLC) was performed to identify classes of compounds present in T. violacea. xix Antioxidant activity of T. violacea was determined qualitatively using a dot-plot and quantitatively using a DPPH radical scavenging activity assay. Ascorbic acid was used as the standard. Anti-diabetic properties of T. violacea were assessed using an α- amylase inhibition assay and an α- glucosidase inhibition assay. Acarbose was used as the standard for these assays. The anti-Alzheimer properties of T. violacea leaf extracts was determined using and acetylcholinesterase (AChE) inhibition assay. Donepezil was used as the standard for this assay. The DPPH radical scavenging activity, the α- amylase inhibition assay, the α- glucosidase inhibition assay and the AChE inhibition assay was combined with linear regression to determine the IC50 values of the T. violacea extracts and the standards. Statistical analysis was conducted to determine any differences between the plant samples and the standards as well as any differences between the EC and GP sample. Results: The results of the qualitative phytochemical analysis revealed the presence of saponins, flavonoids, tannins, alkaloids, steroids, cardiac glycosides and phenolic compounds present in T. violacea collected from EC and GP. However, their presence in the samples were different based on where the plant was cultivated. The results of the total phenolic content test, revealed that the hexane, acetone and methanol extracts of T. violacea contained phenolic compounds with the highest quantity of phenolic compounds being present in the methanol extracts. Significant statistical difference in total phenolic content between the EC and GP samples were seen for the hexane and methanol extracts. The results of the TLC revealed the presence of multiple bands which confirmed the presence of multiple phytochemicals in T. violacea. All of the extracts of T. violacea from EC and GP, showed antioxidant activity using both the dot-plot and the DPPH radical scavenging activity assay. The highest DPPH radical scavenging activity was seen by the hexane extract of the EC sample of T. violacea. The results showed significant statistical difference between the DPPH radical scavenging activity of the EC and GP samples. , Thesis (Msc (Pharmacy)) -- Faculty of Pharmacy, Pharmacy, 2024
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Date Issued: 2024-10-11

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A retrospective study of antimicrobial prescribing practices in paediatric patients at the Mahalapye District Hospital, Central Botswana

- Nyawera, Angella

Authors: Nyawera, Angella
Date: 2022-04-06
Subjects: Anti-infective agents Botswana Mahalapye , Drug resistance , Pediatrics Botswana Mahalapye , Pediatrics Formulae, receipts, prescriptions , Drugs Prescribing Moral and ethical aspects
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/290682 , vital:56774
Description: Background: The development of antimicrobial resistance (AMR) has been linked to the increased and irrational use of antimicrobial medicines. The aim of this study was to investigate the antimicrobial prescribing practices in the paediatric medical ward at Mahalapye District Hospital (MDH) in Botswana and to determine whether antimicrobial stewardship (AMS) measures were being implemented at the hospital. Methods A cross-sectional, descriptive, mixed methods, observational approach was taken in this study. The study site was the paediatric medical ward (PMW) at MDH. Information about the antimicrobials prescribed for paediatric patients from January 2018 to December 2018 was collected from patients’ information files and compared to national antimicrobial prescribing guidelines to determine prescribers’ adherence. Qualitative semi-structured interviews were conducted with members of staff at MDH to determine whether antimicrobial stewardship (AMS) measures were adopted at the hospital. Results A total of 278 patients were included in this study, 12 of these were admitted twice during the study period. In total 290 admissions were analysed, with 659 antimicrobial medicines prescribed. The most common diagnoses were pneumonia (36.9%), acute gastroenteritis (20.7%), upper respiratory tract infections (3.4%), and bronchiolitis (3.1%). The most prescribed antimicrobials were ampicillin (21.4%), gentamicin (21.2%), and cefotaxime (8.3%). Adherence to guidelines was relatively good, with 82.7% of antimicrobials prescribed for the patients in the study having been prescribed in compliance with the national prescribing guidelines. The semi-structured interviews highlighted the fact that staff knew about AMS and AMR in general, however awareness of an AMS committee at MDH varied. The AMS committee was a multidisciplinary committee, which was a subcommittee of the Drugs and Therapeutics Committee (DTC). Discussion and Conclusion The results suggest that adherence to prescribing guidelines was relatively high compared to other paediatric antimicrobial utilisation studies in African countries. Prescribing of antimicrobial medicines was consistent with other African countries. The long period of time that it takes for microbiological test results to become available means that most prescribers rely on empirical prescribing. The antimicrobial committee is a multidisciplinary committee with defined roles for its members, consistent with international guidelines for implementing an AMS committee at a hospital. , Thesis (MPharm) -- Faculty of Pharmacy, Pharmacy, 2022
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Date Issued: 2022-04-06

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Fabrication and characterization of ciprofloxacin loaded niosomes for transtympanic delivery

- Mhlanga, Asavela

Authors: Mhlanga, Asavela
Date: 2022-04-06
Subjects: Drug delivery systems , Liposomes , Ciprofloxacin , Quinolone antibacterial agents , Drug carriers (Pharmacy) , Drug stability , Lamellarity‎ , Niosomes‎
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/290715 , vital:56777
Description: Ciprofloxacin (CPH) is a broad-spectrum antibiotic used to treat bone, joint, and skin infections. It is commercially available as an extended-release tablet and as a cream dosage form. CPH is a bactericidal active pharmaceutical ingredient (API) of the fluoroquinolone drug class. It inhibits deoxyribonucleic acid (DNA) replication by inhibiting bacterial DNA topoisomerase and DNA gyrase enzymes. Common adverse effects include nausea, vomiting, unusual fatigue, pale skin, and may increase the risk of tendinitis, which could be a major concern. CPH is, according to the Biopharmaceutics Classification System (BCS), classified as a BCS class IV drug exhibiting low oral bioavailability, low solubility, and intestinal permeability. CPH was chosen as a good candidate for the study because of its stability in solutions, its low molecular weight (331.4 g/mol), and its moderate lipophilicity (log P = 0.28) [16]. The use of conventional ear drops in the ear is effective, avoids hepatic first metabolism and extensive protein binding and may reduce adverse effects as a low dose may be used to achieve a therapeutic effect. However, conventional ear drops and oral antibiotics have a long onset of action and have to be taken/applied in short intervals. For convenience and assurance of a long residence time in the ear, CPH may be delivered by using a niosomal formulation, a liquid at room temperature, to allow administration into the ear without the need to constantly apply the ear drops for long periods of time. A simple, rapid, precise, accurate, reproducible, and specific reversed-phase high-performance liquid chromatography (RP-HPLC) method using ultraviolet (UV) detection for the quantitation of CPH was developed and optimized using a central composite design (CCD). The method was validated using International Conference on Harmonisation (ICH) guidelines and was found to be linear, precise, accurate, and specific for the analysis of CPH. Since the method is specific, it was used to quantify CPH in commercial and experimental formulations and monitor CPH released during in-vitro release testing. The compatibility of CPH and potential excipients was investigated during preformulation studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) to identify and select suitable excipients for use during formulation development activities. No apparent interactions were evident between CPH, and the excipients tested. The probe sonication method was used to manufacture CPH loaded niosomes using different surfactants/surfactant combinations, and a combination of Tween® 80: sodium lauryl sulfate (SLS) was found to be the best composition in terms of both entrapment efficiency and Zeta potential. The limits for the independent input variables used for the manufacture included amplitude, sonication time, and amount of cholesterol were determined. Design of experiments (DOE) was used to design the study. The input variables investigated included amplitude, amount of cholesterol, and sonication time. The output or responses monitored included Zeta potential, vesicle size, polydispersity index (PDI), and entrapment efficiency. Non-ionic surfactant systems are predominantly stabilized by steric stabilization, and there is only a minor electrostatic element from adsorbed hydroxyl ions. With the inclusion of SLS it is to be expected that Zeta potential will be a contributing factor. DOE using Box-Behnken design (BBD) and response surface methodology (RSM) in addition to Artificial Neural Networks (ANN) were used for the optimization of the formulation. The optimized formulation had a composition of 1 g cholesterol, 1 g of Tween® 80, 1 g of SLS and was prepared at an amplitude of 11.294 % with a sonication time of 3.304 minutes. The formulation exhibited zero-order release kinetics and had an average pH of 7.45. The formulation was stored at 4 ℃ and 25 ℃ and was assessed for vesicle size, entrapment efficiency, Zeta potential, colour, lamellarity, and PDI every 7 days for 4 weeks. The lead formulation stored at 4 ℃ was more stable than the formulation at 25 ℃ in terms of entrapment efficiency, PDI and vesicle size during the 4-week period. CPH loaded niosomes for transtympanic delivery in the treatment of otitis media were developed and optimized. The technology exhibits sustained release of CPH and has the potential for further development and optimization. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2022
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Date Issued: 2022-04-06

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Pharmacists’ attitudes and perception of using pictograms as a communication tool in practice

- Okeyo, Sam Juma

Authors: Okeyo, Sam Juma
Date: 2022-04-06
Subjects: Picture-writing South Africa , Communication in public health South Africa , Pharmacists South Africa Attitudes , Health literacy South Africa , Patient education South Africa , Structural equation modeling , ‎Theory of planned behavior
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/290693 , vital:56775
Description: Pictograms, when used in conjunction with verbal and written information, are known to be effective in improving comprehension and recall of medicines information and in supporting communication between healthcare professionals and patients. However, pictograms are seldom used in routine pharmacy practice, and little is known about pharmacists’ opinions of pictograms and their intention to possibly incorporate pictograms into routine practice. This study aimed to investigate pharmacists’ opinions relating to pictograms as a communication tool, and, by applying the Theory of Planned Behaviour (TPB), to explore their intention to use pictograms in pharmacy practice as well as the barriers to their use. The quantitative study design involved a two-phase approach. Phase 1 was a descriptive, cross-sectional online national survey of pharmacists. The 70-item, four-section survey was primarily based on the constructs of TPB, which included attitude, intention, subjective norm, and perceived behavioural control. The last survey section recruited pharmacists for a follow-up Phase 2 survey. Following a pilot study, the survey was emailed to all pharmacists registered with the South African Pharmacy Council. Descriptive statistics for survey items were generated. Pearson correlation investigated the correlation between participant characteristics, familiarity with pictograms and use of pictograms in practice. Structural Equation Modelling (SEM) determined if there was a significant relationship between attitude, subjective norm and perceived behavioural control with intention to use pictograms. A total of 426 pharmacists responded to the Phase 1 survey. Most pharmacists were familiar with the term ‘pictogram’; however, over three-quarters of pharmacists had never observed pictograms being routinely used in a pharmacy setting. When presented with pictograms designed for a low health literate population, most pharmacists thought the design and overall look of the pictograms would be easy for most patients in South Africa to understand (71.6 ± 24.0). Two-thirds of pharmacists (65.0 ± 30.6), felt that pictograms should be used for all patient populations. More than 85% of pharmacists agreed that pictograms should be used for dosage instructions, auxiliary or additional information, warnings, and storage instructions. However, fewer (58-68%) felt that indication, side effects and risk communication information should be accompanied by pictograms. Pharmacists demonstrated positive attitudes towards using pictograms in practice (mean = 4.2 ± 0.9; range: 1 - 5), while perceived behavioural control (mean = 3.0 ± 1.2; range: 1 - 5), subjective norm (mean = 3.8 ± 1.0; range 1 - 5) and intention (mean = 3.3 ± 1.0; range 1 - 5) were all neutral. Attitude (β = -0.25, p < 0.117), however, was not a significant predictor of intention while perceived behavioural control (β = -0.83, p < 0.000) presented with a significant negative correlation with intention. Subjective norm (β = 0.57, p <0.000) was the strongest predictor of intention. Scale reliability ranged from 0.770 to 0.865 for the TPB constructs. Phase 2 aimed to expand on, and further investigate Phase 1 findings relating to current and intended pharmacist behaviour and opinions concerning pictogram usage. As Phase 2 looked to investigate issues in greater depth, questions included open-ended response options. The survey link was emailed to all pharmacists who had voluntarily offered to participate in Phase 2. Frequency data for all questions were generated, and content analysis was undertaken for the free-response comments offered by pharmacists. A total of 35 pharmacists responded to the Phase 2 survey. Most pharmacists who routinely used pictograms initiated their use with support from pharmacists’ colleagues (8/12) and their supervisor/manager (6/7). Pharmacists who stated their intention to use pictograms anticipated receiving support from their pharmacists' colleagues (18/23) and manager/supervisor (15/23). All 12 pharmacists who were routinely using pictograms reported a positive effect on patient communication, with almost all having encountered no negative aspects of using pictograms (11/12). Almost all pharmacists intending to use pictograms could foresee benefits from their use (22/23). Misinterpretation of pictograms was a prevalent barrier common to both pharmacists routinely using pictograms and to those intending to use pictograms. Increased workload was regarded as a prevalent barrier only by pharmacists intending to use pictograms. This study was the first national study of pharmacists to investigate their opinion of pictograms and their use and to adopt a theoretical approach to consider pharmacist intention to use pictograms in routine pharmacy practice. Pharmacists generally expressed positive attitudes to pictograms but showed inadequate understanding of pictogram use. Pharmacists using pictograms reported the positive effect of pictograms on their patient communication, whereas those planning to use pictograms could foresee the benefits of using pictograms despite regarding increased workload as a barrier. As the strongest predictor of intention was subjective norm, this construct should therefore be targeted to motivate pharmacists to adopt the use of pictograms. , Thesis (MPharm) -- Faculty of Pharmacy, Pharmacy, 2022
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Date Issued: 2022-04-06

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