Research Articles (Pharmacology)
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Item Expert consensus on vitamin B6 therapeutic use for patients : guidance on safe dosage, duration and clinical management(Dove Medical Press, 2025-04) Schellack, Natalie; Yotsombut, Kitiyot; Sabet, Arman; Nafach, Jalal; Hiew, Fu Liong; Kulkantrakorn, KongkiatPURPOSE : Vitamin B6 is a crucial water-soluble vitamin found in many foods and is involved in numerous physiological processes, including neurotransmitter synthesis and nervous system function. Although essential for overall health, both deficiency and excessive intake of vitamin B6 may lead to health complications, particularly peripheral neuropathy. This consensus statement aims to provide healthcare professionals with clear guidance on the safe and effective use of vitamin B6, focusing on its benefits, risks, recommended dosages, and treatment course. METHODS : This consensus statement was developed using a Delphi approach involving a panel of six experts from various medical specialties. This process includes a comprehensive literature review, two rounds of anonymous online surveys, and a virtual expert roundtable discussion. The GRADE approach was used to assess the quality of evidence for each recommendation. RESULTS : The expert panel reached consensus on five key statements. These key recommendations encompass the function of vitamin B6, complications due to vitamin B6 deficiency, dosage recommendations, adverse events, and monitoring guidance throughout the course of treatment. A washout period of 20– 40 days for the complete clearance of vitamin B6 was calculated based on pharmacokinetic parameters. A clinical pathway for managing patients who might benefit from vitamin B6 treatment was proposed. CONCLUSION : This consensus statement highlights the importance of recognizing the benefits and potential risks of vitamin B6. While the therapeutic dosage of vitamin B6 can be beneficial to treat deficiency, excessive intake can lead to adverse effects. This statement emphasizes the need for individualized patient care considering factors such as medical history, lifestyle, and potential drug interactions. Further research is needed to establish clearer dosage guidelines, understand the mechanisms of vitamin B6-induced neurological side effects, and optimize patient outcomes.Item Update on the pharmacological management of neurodegenerative diseases : Alzheimer's disease(Medpharm Publications, 2024) Flepisi, Brian Thabile; Hanser, S.; Balmith, Marissa; brian.flepisi@up.ac.zaNeurodegenerative diseases (NDDs) are the most common causes of morbidity and cognitive impairment, particularly among the elderly population worldwide. Due to increasing life expectancy, there has been an increase in the prevalence of NDDs. One of the most common NDDs is Alzheimer’s disease (AD), which is characterised by a complex, multifactorial irreversible aetiology, including the progressive loss of neurons. It is also the most common cause of dementia. Pathologically, AD is associated with the presence of amyloid plaques and intracellular neurofibrillary tangles. The management of AD focuses mainly on establishing an early, accurate clinical diagnosis, early drug administration, treatment of comorbidities and dementia-related complications, as well as treatment of behavioural and psychological symptoms. There is currently no cure for AD, and the currently United States Food and Drug Administration (US-FDA) approved drugs only offer symptomatic relief aiming to improve cognitive and behavioural symptoms; however, they do not target the underlying AD pathology or prevent neuronal degeneration. The current US-FDA approved drugs used for the management of AD include acetylcholinesterase inhibitors (donepezil, galantamine, and rivastigmine), N-methyl-D-aspartate (NMDA) receptor antagonist (memantine), and monoclonal antibody against Aβ (Lecanemab). It should be noted that all these approved drugs only assist in the management of symptoms; however, they do not prevent neuronal loss, brain atrophy, and progressive deterioration of cognition associated with AD. To curb the increasing prevalence of AD, new therapeutic strategies are required, including the development of gene therapy, drugs targeting Aβ, and drugs targeting neuronal hyperexcitability among others.Item The misuse of analgesics and nonsteroidal anti-inflammatories in runners(Medpharm Publications, 2024) Esterhuizen, C.; Cordier, WernerGlobal participation in running has continued to grow over the last decade, with millions of people running weekly, regardless of distance. These events, particularly endurance running events, require months of progressive training and load adjustment, which, combined with other factors, increase the risk of developing running-related injuries. Inflammation is a natural biological response important for healing in musculoskeletal tissue; however, it may also contribute to the unpleasant experience of pain. Runners may suffer from exercise-induced pain and inflammation, necessitating using analgesics and nonsteroidal anti-inflammatories. Unfortunately, the inappropriate use of these drugs is frequently seen in athletes, which may impact their recovery after injury or general health status. This review presents in brief the current knowledge of running-related pathology and treatment thereof, including considerations of its misuse.Item The impact of unprofessional behaviour on patient safety in South Africa : two cautionary tales(Medpharm Publications, 2024) Schellack, Natalie; Maimin, J.; Kriel, M.; Moodley, S.; Padayachee, N.; natalie.schellack@up.ac.zaIn terms of the Rules relating to the Code of Conduct, every pharmacist’s prime concern in the performance of his/her professional duties must be for the wellbeing of both the patient and other members of the public. A pharmacist must uphold the honour and dignity of the profession and may not engage in any activity which could bring the profession into disrepute.Pharmacists engaging in unprofessional conduct or conduct where their regard for their profession is disrespectful, may be involved in activities such as the selling of counterfeit medicines, dispensing medication without prescription, and selling excessive quantities of medicines liable for misuse or abuse, i.e. drug trafficking. These actions can be attributed to factors such as financial incentives, inadequate training, or personal challenges, none of which are acceptable. These pharmacists are viewed as rogue pharmacists with severe implications for patient safety and significant risk of bringing the profession into disrepute.There are also instances where pharmacists make dispensing errors, supplying incorrect medicines, incorrect strength of medicines or incorrect dosage instructions. These errors are generally inadvertent but can obviously have a negative impact on patient safety. As the custodian of medicine, it is crucial that the pharmacist makes every effort to prevent medication errors. Pharmacists must be aware of areas where the chances of dispensing errors are high, especially those caused by look-alike sound-alike (LASA) medications, as they can lead to adverse reactions or even death. Preventing LASA medication errors requires awareness, generic prescribing, pop-up alerts in computer systems, eye-catching labels and warnings, patient education, and the establishment of process and outcome measures. Pharmacists can also organise high-risk LASA drugs on separate shelves and implement double-checking systems for accuracy when dispensing medications.Dispensing errors can have severe consequences for the pharmacist, including monetary fines, registration suspension or removal, and public scrutiny. The misuse and abuse of codeine-containing medications pose significant health risks and pharmacists play a crucial role in harm reduction.Measures to address codeine overuse, misuse and abuse include enhanced regulatory measures, public health interventions, surveillance,training, and education. Without some form of centralised database, it is very challenging for a pharmacist to manage this problem as individuals utilise different pharmacies and their medication history is not linked. To address this problem, pharmacists can participate in initiatives such as the Codeine Care Initiative, a centralised data base of codeine-containing medicine use. This allows the monitoring of frequent purchasers of codeine and gives the pharmacist an opportunity to address codeine misuse at the point of dispensing.Item Stepping up : a pharmacist’s role in managing diabetes and foot ulcers(Medpharm Publications, 2024) Mlambo, Shamiso Shelter; Ncube, Keith Ntokozo; Parkar, Hafiza; shamiso.mlambo@up.ac.zaDiabetes mellitus (DM) is a significant global health problem, with over 537 million adults affected in 2021. A crucial complication of DM is diabetic foot ulcers (DFUs), which result from nerve damage and impaired circulation, leading to loss of function and high medical costs. The role of pharmacists in managing diabetes and DFUs has evolved from strictly dispensing medication to being healthcare providers that are actively involved in patient education on glycaemic control, wound care strategies, and promotion of medication adherence. Treatment of DFUs is mainly focused on maintaining a moist wound environment, preventing infection and pressure offloading. This article highlights the essential role of pharmacists in a multidisciplinary healthcare team to enhance patient outcomes by applying their expertise to reduce diabetes-related complications such as DFUs.Item An overview of thyroid disorders and their management(Medpharm Publications, 2024) Schellack, G.; Schellack, Natalie; De Moura-Cunningham, C.; natalie.schellack@up.ac.zaDisorders of the thyroid gland are frequently encountered in the clinical practice setting and typically fall into one of two categories, namelyhypothyroidism (i.e. deficient levels of circulating thyroid hormone), or hyperthyroidism (or thyrotoxicosis) that involves abnormally highlevels of thyroid hormone in the blood stream. This article provides a high-level overview of thyroid function, the two major pathophysiologicalabnormalities of the thyroid gland, as well as treatment modalities aimed at managing patients with thyroid pathology. In addition, a briefdescription of two major autoimmune conditions of the thyroid gland, namely Graves’ disease and Hashimoto’s thyroiditis, is also provided.Item Evaluation of the labelling adherence of the food-associated effects of selected pharmacotherapy(Medpharm Publications, 2024) Mbonani, N.; Olivier, Natascha; Cordier, Werner; werner.cordier@up.ac.zaBACKGROUND : Pharmacotherapy and dietary interventions often work together to enhance patient treatment and outcomes. Yet, food-associated effects, including food-drug interactions, remain a significant challenge, especially for oral pharmacotherapy. These interactions can undermine the safety and efficacy of medications and negatively impact patients’ nutritional status. Despite medicinal package inserts being the primary source of such information, studies from other countries highlight inconsistencies and inadequacies in the labelling of food-drug interactions. In South Africa, this critical issue remains largely unexplored, leaving potential risks unaddressed. The study aimed to evaluate the adherence of professional and patient information leaflets to labelling regulations concerning food-associated effects, providing some insight on a crucial yet often overlooked aspect of patient safety. METHODS : The South African Health Products Regulatory Authority (SAHPRA) labelling guidelines were used to evaluate the adherence to labelling of food-associated effects in the professional and patient information leaflets of warfarin, statins, fluoroquinolone and tetracycline antibiotics. RESULTS : The leaflets showed partial adherence to SAHPRA labelling guidelines. Food-drug interaction information was either lacking or inadequately described, particularly in relation to the mechanism of interaction, clinical outcomes, or recommendations. Although the information was mostly presented under appropriate headings, it was not always available under recommended sections and rarely cross-referenced. CONCLUSIONS : The labelling of food-associated effects in the evaluated professional and patient information leaflets was partially adherent to SAHPRA labelling guidelines, which may hinder effective guidance for healthcare professionals and patients. Although a small sample, non-adherence is evident and suggests bolstering is needed to mitigate potentially clinically significant interactions.Item Less is more? A review of psilocybin microdosing(Sage, 2024-10) Savides, Isabella A.; Outhoff, KimBACKGROUND : The applications of psilocybin, derived from 'magic mushrooms,' are vast, including a burgeoning practice known as microdosing, which refers to the administration of sub-hallucinogenic doses of psychedelic substances to obtain benefits without experiencing significant cognitive and perceptual distortion. However, current research is fairly new with several limitations and gaps that hinder adequate conclusions on its efficacy. AIMS : This semi-structured review aimed to identify and highlight research gaps in the field of psilocybin microdosing for future research. METHODS : A Preferred Reporting Items for Systematic Reviews and Meta-Analyses based strategy was employed, utilizing a chain of keywords and key phrases across multiple databases, augmented by a cross-sectional Google search for relevant grey literature in the form of the top 10 search results. A total of 40 studies and 8 unique websites were identified, summarized and tabulated into four distinct categories, namely non-clinical, clinical, observational and anecdotal evidence. RESULTS : The majority of available evidence originates from observational studies, while non-clinical and clinical study findings remain comparatively sparse and inconsistent. Web-based findings were consistent with current research findings. Key research gaps were highlighted: the imperative for more randomized placebo-controlled trials, exploration of dose-response ranges, psychological and personality testing of participants, utilization of active placebos, greater diversity in study populations, an increase in psilocybin-exclusive microdosing studies and the refinement of animal models. CONCLUSION : Definitive conclusions regarding the efficacy of psilocybin microdosing remain elusive, emphasizing the need for further study. Numerous research gaps necessitate consideration for future investigations.Item Status and implications of the knowledge, attitudes and practices towards AWaRe antibiotic use, resistance and stewardship among low- and middle-income countries(Oxford University Press, 2025-04) Saleem, Zikria; Moore, Catrin E.; Kalungia, Aubrey C.; Schellack, Natalie; Ogunleye, Olayinka; Chigome, Audrey; Chowdhury, Kona; Kitutu, Freddy Eric; Massele, Amos; Ramdas, Nishana; Orubu, E. Sam; Cook, Aislinn; Khuluza, Felix; Zaranyika, Trust; Funiciello, Elisa; Lorenzetti, Giulia; Nantamu, Miriam; Parajuli, Ayuska; Kurdi, Amanj; Nabayiga, Hellen; Jairoun, Ammar Abdulrahman; Haque, Mainul; Campbell, Stephen M.; Van der Bergh, Dena; Godman, Brian; Sharland, MikeBACKGROUND : There are concerns globally with rising rates of antimicrobial resistance (AMR), particularly in low- and middle-income countries (LMICs). AMR is driven by high rates of inappropriate prescribing and dispensing of antibiotics, particularly Watch antibiotics. To develop future interventions, it is important to document current knowledge, attitudes and practices (KAP) among key stakeholder groups in LMICs. METHODS : We undertook a narrative review of published papers among four WHO Regions including African and Asian countries. Relevant papers were sourced from 2018 to 2024 and synthesized by key stakeholder group, country, WHO Region, income level and year. The findings were summarized to identify pertinent future activities for all key stakeholder groups. RESULTS : We sourced 459 papers, with a large number coming from Africa (42.7%). An appreciable number dealt with patients’ KAP (33.1%), reflecting their influence on the prescribing and dispensing of antibiotics. There was marked consistency of findings among key stakeholder groups across the four WHO Regions, all showing concerns with high rates of prescribing of antibiotics for viral infections despite professed knowledge of antibiotics and AMR. There were similar issues among dispensers. Patients’ beliefs regarding the effectiveness of antibiotics for self-limiting infectious diseases were a major challenge, although educational programmes did improve knowledge. The development of the AWaRe (Access, Watch and Reserve) system, including practical prescribing guidance, provides a future opportunity for the standardization of educational inputs. CONCLUSIONS : Similar KAP regarding the prescribing and dispensing of antibiotics across LMICs and stakeholder groups presents clear opportunities for standardization of educational input and practical training programmes based on the AWaRe system.Item Defining and responding to the contextual drivers for implementation of antimicrobial stewardship in 14 neonatal units in South Africa(Oxford University Press, 2025-01) Van Den Bergh, Dena; Charani, Esmita; Dramowski, Angela; Annor, Ama Sakoa; Gijzelaar, Michelle; Messina, Angeliki; Van Jaarsveld, Andriette; Goff, Debra A.; Prusakov, Pavel; Balfour, Liezl; Bekker, Adrie; Cassim, Azraa; Govender, Nelesh P.; Holgate, Sandi L.; Kolman, Sonya; Tootla, Hafsah; Schellack, Natalie; Reddy, Kessendri; Fisher, Christine; Conradie, Lucinda; Van Niekerk, Anika; Laubscher, Anje; Alexander, Pearl; Naidoo, Thanusha; Dippenaar, Magdel; Bamford, Colleen; Brits, Sharnel; Chirwa, Pinky; Erasmus, Hannelie; Ekermans, Pieter; Rungen, Lerina; Kriel, Teresa; Mawela, Dini; Mjekula, Simthembile; Nchabeleng, Maphoshane; Nhari, Ronald; Janse van Rensburg, Marli; Sanchez, Pablo J.; Brink, Adrian; NeoAMS Study TeamBACKGROUND : Research on the contextual drivers of antimicrobial stewardship (AMS) programme interventions in neonatal units is limited. METHODS : As part of a prospective mixed-methods multidisciplinary neonatal AMS (NeoAMS) interventional study in 14 South African hospitals, we applied a three-phased process to assess implementation barriers and contextual drivers experienced by participating health professionals. The study included: (Phase one; P1) a survey of pre-intervention barriers and enablers; (P2) written feedback during the study intervention phase; and (P3) semi-structured exit interviews. RESULTS : Respondents to the P1 survey (n = 100) identified 15 barriers, 9 in the domain of personnel resources, including staffing, time and workload constraints. Other barriers related to limited access to antimicrobial use and surveillance trends, complexity of neonatal care, absence of multidisciplinary team (MDT) AMS and change resistance. For P2, written feedback during implementation (n = 42) confirmed that the MDT approach facilitated systems changes, including policy adaptations, process improvements, strengthened infection control practices, and expansion of AMS MDT roles. MDT benefits were described as aligned team purpose, improved communication, and knowledge sharing. Reported challenges included time to meet and building trust. In P3 interviews (n = 42), improved interpersonal communication, trust, personal growth and confidence building were cited as highlights of working in multidisciplinary AMS teams. Extending the MDT approach to other hospitals, training more health professionals in AMS and increasing management involvement were identified as priorities going forward. CONCLUSIONS : Understanding the organizational and interprofessional context for NeoAMS implementation enabled an MDT approach to develop and optimize neonatal AMS with potential for adoption in similar resource-constrained settings.Item Evaluating blood-brain barrier permeability, cytotoxicity, and activity of potential acetylcholinesterase inhibitors : in vitro and in silico study(Wiley, 2024-12) Maboko, Lerato Mamabote; Theron, A.; Panayides, J._L.; Cordier, Werner; Fisher, D.; Steenkamp, VanessaAcetylcholinesterase inhibitors (AChEIs) remain the first-line treatment for Alzheimer's disease. However, these drugs are largely symptomatic and often associated with adverse effects. This study aimed to evaluate novel pharmacophores for their in vitro AChEI activity, blood–brain barrier (BBB) permeability, and cytotoxic potential, hypothesizing that a combination of AChEIs could enhance symptom management while minimizing toxicity. A library of 1453 synthetic pharmacophores was assessed using in vitro and in silico methods to determine their feasibility as an inhibitor of the AChE enzyme. An in-house miniaturized Ellman's assay determined acellular AChEI activities, while pharmacokinetic properties were evaluated using the SwissADME web tool. The combinational effects of in silico BBB-permeable pharmacophores and donepezil were examined using a checkerboard AChEI assay. Cytotoxicity of active compounds and their synergistic combinations was assessed in SH-SY5Y neuroblastoma and bEnd.5 cells using the sulforhodamine B assay. Cellular AChEI activity of active in silico BBB-permeable predicted compounds was determined using an SH-SY5Y AChE-based assay. An in vitro BBB model was used to assess the effect of compounds on the integrity of the bEnd.5 monolayer. Out of the screened compounds, 12 demonstrated 60% AChEI activity at 5 μM, with compound A51 showing the lowest IC50 (0.20 μM). Five compounds were identified as BBB-permeable, with the donepezil-C53 combination at ¼IC50 exhibiting the strongest synergy (CI = 0.82). Compounds A136 and C129, either alone or with donepezil, showed cytotoxicity. Notably, compound C53, both alone and in combination with donepezil, demonstrated high AChEI activity and promising BBB permeability, warranting further investigation.Item Pilot study to evaluate patients' understanding of key terms and aspects of antimicrobial use in a rural province in South Africa : findings and implications(Wolters Kluwer Medknow Publications, 2025-01) Sono, Tiyani Milta; Mboweni, Veronica; Jelic, Ana Golic; Campbell, Stephen M.; Markovic-Pekovic, Vanda; Ramdas, Nishana; Schellack, Natalie; Kumar, Santosh; Godman, Brian; Meyer, Johanna C.INTRODUCTION : Antimicrobial resistance (AMR) is a global concern, necessitating the understanding of utilisation patterns and their rationale. Pilot studies have been conducted in a rural province in South Africa to determine the extent of self-purchasing of antibiotics by patients from independent and chain pharmacies. It is imperative to understand the extent of knowledge and concerns of patients regarding the key aspects of antibiotic use and AMR, and potential language barriers, when pharmacists and their assistants are discussing the key aspects with patients. Consequently, the aim was to pre-test a patient questionnaire translated in three native languages building on the findings from the English language pilot. MATERIALS AND METHODS : The English patient questionnaire (Parts 1 and 2) was translated to Sepedi, Tshivenda and Xitsonga. In total 30 patients were interviewed (5/language for Part 1 and Part 2 respectively) when leaving 10 chain and independent pharmacies. This was followed by interviews with patients to evaluate their understanding of questions and key concepts. RESULTS : Eleven of 15 patients interviewed for Part 1 received antibiotics, including 8 without a prescription. Only independent pharmacies (8/10) dispensed antibiotics without prescriptions. Interviews revealed concerns about antibiotic knowledge and AMR and that certain terms including ‘antibiotic’ and ‘AMR’ posed challenges with patient understanding of the purpose of antibiotics. For instance, one patient self-purchased antibiotics for ‘cleansing’ of sexually transmitted infections. The questionnaires in the native languages were subsequently revised so that explanations for terms, including ‘antibiotic’ and ‘AMR’ will be provided in the main study. CONCLUSION : Similar to the previous pilot studies, self-purchasing of antibiotics was observed among independent pharmacies, although at varying rates, with similar indications. Continued health literacy education for pharmacists and patients, especially with native language communication, are needed to address current challenges and will be explored in the main study.Item The role of patients with addressing inappropriate dispensing of antibiotics without a prescription especially in developing countries(Wolters Kluwer Medknow Publications, 2025-01) Sono, Tiyani Milta; Schellack, Natalie; Godman, BrianAntimicrobial resistance (AMR) is a growing global concern, significantly impacting on morbidity, mortality and healthcare costs, especially in low- and middle-income countries (LMICs).Item Antimicrobial therapeutic drug monitoring in critically ill adult patients : an international perspective on access, utilisation, and barriers(Elsevier, 2024-08) Williams, Paul G.; Cotta, Menino Osbert; Tabah, Alexis; Sandaradura, Indy; Kanji, Salmaan; Scheetz, Marc H.; Imani, Sahand; Elhadi, Muhammed; Pardos, Sònia L.; Schellack, Natalie; Sanches, Cristina; Timsit, Jean‑Francois; Xie, Jiao; Farkas, Andras; Wilks, Kathryn; Roberts, Jason A.BACKGROUND: Therapeutic drug monitoring (TDM) is an effective method for individualising antimicrobial therapy in critically ill patients. The 2021 ADMIN-intensive care unit survey studied a wide range of intensive care unit clinicians worldwide to gain their perspectives on antimicrobial TDM. This article reports the responses from this survey relating to TDM access, utilisation, and barriers. METHODS: An online survey consisted of multiple-choice questions and 5-point Likert scales. The survey examined respondent’s access to minimum inhibitory concentration (MIC) results, drug assays, and dosing software, as well as barriers to TDM. RESULTS: The survey included 538 clinicians from 409 hospitals in 45 countries, with 71% physicians and 29% pharmacists. Despite most respondents having access to assays, 21% and 26% of respondents lacked access to vancomycin and aminoglycosides, respectively. In lower-income countries, almost 40% reported no access. Delayed drug assay turnaround time was the most significant barrier to TDM, particularly in lower-income countries. Routine access to MIC results was unavailable for 41% of respondents, with 25% of lower-income country respondents having no access to MIC or susceptibility reports. CONCLUSIONS: This global survey indicated that consistent TDM usage is hindered by assay access in some sites and the timeliness of assay results in others. Addressing barriers to TDM, particularly in low-income countries, should be a priority to ensure equitable access to affordable TDM.Item Sodium, potassium-adenosine triphosphatase as a potential target of the anti-tuberculosis agents, clofazimine and bedaquiline(MDPI, 2024-12-04) Mmakola, Khomotso Madimetsa Shelboy; Balmith, Marissa; Steel, Helen Carolyn; Said, Mohamed; Potjo, Moliehi; Van der Mescht, Mieke Adri; Hlatshwayo, Nomsa; Meyer, Pieter Willem Adriaan; Tintinger, Gregory Ronald; Anderson, Ronald; Cholo, Moloko C.Multidrug-resistant tuberculosis (MDR-TB) patients are treated with a standardised, short World Health Organization (WHO) regimen which includes clofazimine (CFZ) and bedaquiline (BDQ) antibiotics. These two antibiotics lead to the development of QT prolongation in patients, inhibiting potassium (K+) uptake by targeting the voltage-gated K+ (Kv)11.1 (hERG) channel of the cardiomyocytes (CMs). However, the involvement of these antibiotics to regulate other K+ transporters of the CMs, as potential mechanisms of QT prolongation, has not been explored. This study determined the effects of CFZ and BDQ on sodium, potassium–adenosine triphosphatase (Na+,K+-ATPase) activity of CMs using rat cardiomyocytes (RCMs). These cells were treated with varying concentrations of CFZ and BDQ individually and in combination (1.25–5 mg/L). Thereafter, Na+,K+-ATPase activity was determined, followed by intracellular adenosine triphosphate (ATP) quantification and cellular viability determination. Furthermore, molecular docking of antibiotics with Na+,K+-ATPase was determined. Both antibiotics demonstrated dose–response inhibition of Na+,K+-ATPase activity of the RCMs. The greatest inhibition was demonstrated by combinations of CFZ and BDQ, followed by BDQ alone and, lastly, CFZ. Neither antibiotic, either individually or in combination, demonstrated cytotoxicity. Molecular docking revealed an interaction of both antibiotics with Na+,K+-ATPase, with BDQ showing higher protein-binding affinity than CFZ. The inhibitory effects of CFZ and BDQ, individually and in combination, on the activity of Na+,K+-ATPase pump of the RCMs highlight the existence of additional mechanisms of QT prolongation by these antibiotics.Item South African dietitians' knowledge and perceptions of food-drug interactions and factors affecting it(Wiley, 2025-02) Megaw, Christie; Olivier, Natascha; Cordier, Werner; werner.cordier@up.ac.zaBACKGROUND : Dietitians ensure that patients receive tailored medical nutrition therapy to integrate with pharmacotherapy safely. Dietitians require a pharmacological understanding to prevent detrimental food-drug interactions (FDIs). The study investigated dietitians' knowledge of FDIs and their information sourcing. METHODS : A cross-sectional online survey was conducted among registered South African dietitians to assess their knowledge of FDIs, the impact of food timing on drugs, and their sources of FDI information. The questionnaire included demographics, a 12-question knowledge assessment, and a qualitative section on information sourcing. Data from 70 valid responses, collected between 2 August and 19 September 2022, were analysed statistically using analysis of variance and chi-square tests to determine whether associations between knowledge scores and demographic factors were present. RESULTS AND DISCUSSION : Out of 70 responses, most participants were female (97.1%) and 47.1% had over 10 years of experience. The participants primarily worked in the areas of dietetics related to chronic and lifestyle-related disorders (75.7%) across various work settings, including in-patient care (32.8%), out-patient care (41.4%), and multi-disciplinary team environments (31.4%). Although not generalisable due to the low response rate (70 out of the 304 required responses for a 5% margin of error), knowledge deficiencies were observed. A cumulative mean knowledge score of 38.3% was observed, with gaps identified for fundamental FDIs. Drug package inserts (55.7%) and clinical websites (68.6%) were primarily used to source information regarding FDIs; however, the former did not always provide sufficient information. Participants proposed that knowledge deficiencies could be overcome with further education, and the development and/or use of mobile applications or summarisations that elaborate on FDIs. CONCLUSION : Knowledge gaps and uncertainties were identified regarding fundamental FDIs; however, further research is needed to pinpoint the specific sources of these deficiencies and the factors influencing them. To improve dietitians' knowledge of FDIs and ensure alignment with their scope and standard of practice, undergraduate curricula should be bolstered and benchmarked to national needs to facilitate graduate development, and additional learning opportunities provided, such as webinars and continuing professional development (CPD), to allow for continuous education for practicing dietitians. SUMMARY : The study provides insights into potential knowledge deficiencies about food-drug interactions in South African registered dietitians. Food-drug interaction information sources, both academic and nonacademic, need to be supplemented with continuous professional development. Package inserts are often not available or feasible as a source of information on food-drug interactions.Item Glioblastoma cells alter brain endothelial cell homeostasis and tight junction protein expression in vitro(Springer, 2025-01) Mokoena, Xolisile; Mabeta, Peaceful Lucy; Cordier, Werner; Flepisi, Brian ThabileBACKGROUND : Glioblastoma (GBM) is an aggressive therapy-resistant brain tumour that may impacts the integrity of the blood–brain barrier (BBB). The BBB is a protective barrier of the central nervous system formed mainly by endothelial cells. This study aimed to investigate the in vitro effect of GBM cells on the BBB. METHODS : Brain endothelial (bEnd.3) cells were used as a model of the BBB. Glioblastoma-conditioned media (CM) was extracted at the 48-h (h) time-point from the U87 GBM cells and diluted to 40% with fresh media. The effect of the U87-CM collected at 48 h on bEnd.3 cell growth was evaluated following 48 and 72 h of treatment using the xCELLigence system. Additionally, bEnd.3 cell growth was also investigated in a U87 and bEnd.3 co-culture model continuously for 48 h using the xCELLigence system. The migration of bEnd.3 cells was assessed following 48 and 72 h using the migration scratch assay. The barrier integrity was evaluated continuously for 1 h using the transwell permeability, and the tight junction (TJ) protein expression was evaluated using Western blot assay following 48 and 72 h. RESULTS : There was a significant decrease in bEnd.3 cell growth following 32 h (p < 0.05), 40 h (p < 0.01), and 48 h (p < 0.001) of treatment with U87-CM, while co-culturing of bEnd.3 and U87 cells increased cell growth following 16 h (p < 0.05), 24 h (p < 0.001), 32 h (p < 0.01), 40 h (p < 0.001), and 48 h (p < 0.001). The migration of bEnd.3 cells significantly increased following both 24 (p < 0.05) and 48 h (p < 0.01) of treatment with U87-CM. The permeability of bEnd.3 cells co-cultured with U87 for 48 h was significantly increased (p < 0.05) at the 15- and 30-min time points. Furthermore, the expression of ZO-1 and occludin was significantly increased (p < 0.05) in both bEnd.3 cells treated with U87-CM as well as bEnd.3 cells co-cultured with U87 cells. CONCLUSION : The current findings suggest that U87 cells alter the integrity of bEnd.3 cells possibly through the secretomes in the CM and through cell–cell interactions in co-culture models. This may assist in the understanding of the mechanisms by which GBM affects the BBB, which may aid in the management thereof.Item An ethnobotanical survey and pharmacological and toxicity review of medicinal plants used in the management of obesity in the North Central Zone of Nigeria(Wiley, 2025-02) Anyanwu, Gabriel O.; Anzaku, Dorathy; Bulus, Yanga J.; Girgi, Jemimah N.; Donwell, Chinda C.; Ihuma, Jerome O.; Onyeneke, Eusebius C.; Bermano, Giovanna; Steenkamp, VanessaINTRODUCTION : Obesity is increasing worldwide. Due to the unavailability of affordable obesity drugs in most parts of Nigeria, many overweight and obese people rely on medicinal plants to manage obesity. Thus, the aim of this study is to document medicinal plants traditionally used in the treatment and management of obesity in the North Central Zone of Nigeria, determine the plants to which pharmacological assessment of their use in obesity management has not been reported, and assess their toxicity based on the literature. METHODS : Semistructured questionnaires and interviews were used to assess sociodemographic information of the 700 herb sellers/practitioners (100 for each state) who consented to participate in the study. Information gathered on plants that are traditionally used in the management of obesity included administration/dosage, method of preparation, plant part used, method of growth, and plant type. The field study was conducted over a one-year period, from March 2018 to March 2019. Reports of pharmacological activity pertaining to obesity as well as toxicity of the plants were obtained from the literature via scientific databases (Scopus, Web of Science, PubMed, Google Scholar, SciFinder, AJOL, PubChem, and other web sources) after the field survey. RESULTS : A total of 39 families and 70 plant species were used to treat or manage obesity. The majority of plant species used resulted in the family Leguminosae. The relative frequency of citation (RFC) and percentage values for the five most frequently used plants were as follows: Citrus aurantifolia (0.0500; 3.56%), Citrus limon (0.0457; 3.26%), Garcinia kola (0.0429; 3.05%), Zingiber officinale (0.0429; 3.05%), and Allium sativum (0.0414; 2.95%). The majority of the medications were prepared as decoctions (50.5%), and cultivated plants (62.86%) were in the majority of plants used. Results showed that 23 plants have no pharmacological report for antiobesity activities while among the five frequently used plants, only Garcinia kola was reported toxic in preclinical models. CONCLUSIONS : This paper provides a valuable compilation of the plants used in obesity treatment in the study area by indigenous healers, highlights plants with no reported pharmacological activity pertaining to obesity, and indicates the toxicity profile of used plants. However, further studies on the mechanism of action are warranted, especially where no reports were obtained.Item Transitioning to quick response codes for patient information leaflet delivery(Elsevier, 2025-03) Singh, Githa; Brand, S.J. (Sarel); Steenkamp, Vanessa; vanessa.steenkamp@up.ac.zaBACKGROUND : The inclusion of a patient information leaflet (PIL) in medicine packaging is a legal requirement in most countries. OBJECTIVE : To evaluate the feasibility of using quick response (QR) codes for electronic patient information leaflet (ePIL) delivery. METHOD : A mixed-method study based on surveys was conducted at the Tshwane District Hospital in South Africa. The demographics, ability and willingness of patients (330) and pharmacy staff (16) to scan a QR code for a commonly prescribed medicine was captured. A focus group study among 18 regulatory affairs pharmacists gauged their perception of ease of implementation of QR codes. RESULTS : Of the 330 patients, most were 26–55 years of age (67 %) and 70 % were female. Irrespective of patient age and gender, >80 % were willing/ able to scan the QR code and preferred the ePIL (35 %) or ePIL with a hardcopy (45 %). Patients (>96 %) found it easy to read the ePIL (C = 0.487, p < 0.001) and locate the information sought (C = 0.521, p < 0.001). This sentiment was shared by dispensing pharmacy staff: easier to read (C = 0.746, p < 0.05) and locate information (C = 0.630, p < 0.05), with 69 % preferring either the ePIL or ePIL with a hardcopy. All the regulatory affairs pharmacists preferred the ePIL and indicated that it was easy to create a QR code for ePILs. CONCLUSION : Patients, dispensing pharmacy staff, and regulatory affairs pharmacists are willing to transition to ePILs. This makes going green and updating information in real time possible.Item Knowledge, attitudes, motivations and expectations regarding antimicrobial use among community members seeking care at the primary healthcare level : a scoping review protocol(BMJ Publishing Group, 2025-02) Ramdas, Nishana; Meyer, Johanna C.; Schellack, Natalie; Godman, Brian; Turawa, Eunice Bolanle; Campbell, Stephen M.INTRODUCTION : Inappropriate antibiotic use in (primary healthcare, PHC) settings fuels antimicrobial resistance (AMR), threatens patient safety and burdens healthcare systems. Patients’ knowledge, attitudes, motivations and expectations play a crucial role in antibiotic use behaviour, especially in low-income and middle-income countries including South Africa. There is a need to ensure measures of antibiotic use, interventions and future guidance reflect cultural, community and demographic issues associated with patient views to reduce inappropriate use of antibiotics and associated AMR. The objective of this scoping review is to identify key themes surrounding knowledge, attitudes, motivations and expectations among patients and community members regarding antimicrobial use in PHC settings especially in low-income and middle-income countries. METHODS AND ANALYSIS : This scoping review employs a comprehensive search strategy across multiple electronic databases, including OVID, Medline, PubMed and CINHAL, to identify studies addressing patients or community members seeking care at PHC facilities and exploring key drivers of antimicrobial use. The Covidence web-based platform will be used for literature screening and data extraction and the Critical Appraisal Skills Programme qualitative checklist will assess the quality of qualitative papers. Anticipated results will provide an overview of the current evidence base, enabling identification of knowledge gaps. A narrative synthesis of findings will summarise key themes and patterns in patients’ knowledge, attitudes, motivations and expectations related to antibiotic use across studies while considering methodological diversity and limitations. ETHICS AND DISSEMINATION : Ethics approval is not required for this scoping review. The findings of this scoping review will be disseminated through publication in a peer-reviewed journal, presentation at relevant conferences and workshops, and collaboration with policy-makers and healthcare stakeholders.