Browsing by Subject "African"

Now showing 1 - 5 of 5
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    A cost effective RFLP method to genotype Solute carrier organic anion 1B1 (SLCO1B1) c.1929A>C (p.Leu643Phe, rs34671512); a variant with potential effect on rosuvastatin pharmacokinetics
    (BioMed Central, 2018-06-14) Soko, Nyarai D; Masimirembwa, Collen; Dandara, Collet
    Objective: This study describes a restriction fragment polymorphism protocol for rapidly screening the polymorphism SLCO1B1 c.1929A>C in genomic DNA samples. The polymorphism SLCO1B1 c.1929A>C has been associated with increased activity resulting in increased hepatic uptake of drugs. Currently SLCO1B1 c.1929A>C is genotyped using direct sequencing techniques and 5′ nuclease based assays which can be cost prohibiting in resource limited settings. The aim of this study therefore was to design and validate a cost effective RFLP for genotyping the SLCO1B1 c.1929A>C polymorphism. This study was designed to investigate the effect of the polymorphism SLCO1B1 c.1929A>C on interindividual variability in rosuvastatin pharmacokinetics in healthy volunteers of African descent. Results We describe a restriction fragment length polymorphism method to genotype SLCO1B1 c.1929A>C polymorphism using the restriction enzyme Ase1. A student’s t test with Welch correction was used to establish association between the SLCO1B1 c.1929A>C variant and rosuvastatin exposure. The frequency of the SLCO1B1 c.1929C allele amongst Zimbabweans was 6%. The SLCO1B1 c.1929C allele was associated with a 75% reduction (P < 0.001) in rosuvastatin exposure when compared to individuals carrying the wild type SLCO1B1 c.1929A allele. Polymorphism c.1929A>C may therefore play a significant role in rosuvastatin response. The RFLP method is quick and cost effective.
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    A Founder Mutation in MYO7A Underlies a Significant Proportion of Usher Syndrome in Indigenous South Africans: Implications for the African Diaspora
    (Association for Research in Vision and Ophthalmology (ARVO), 2015-10) Roberts, Lisa; George, Siddiqah; Greenberg, Jacquie; Ramesar, Raj
    PURPOSE. Research over the past 25 years at the University of Cape Town has led to the identification of causative mutations in 17% of the 1416 families in the Retinal Degenerative Diseases (RDD) biorepository in South Africa. A low rate of mutation detection has been observed in patients of indigenous African origin, hinting at novel genes and mutations in this population. Recently, however, data from our translational research program showed two unrelated indigenous African families with Usher syndrome (USH), with the same homozygous MYO7A mutation. Therefore, the extent to which this mutation contributes toward the disease burden in South Africa was investigated. METHODS. Cohorts of unrelated indigenous South African probands with different RDD diagnoses were tested for the MYO7A c.6377delC mutation. Familial cosegregation analysis was performed for homozygous probands, clinical data were evaluated, and SNP haplotypes were analyzed. RESULTS. This homozygous MYO7A mutation underlies a remarkable 43% of indigenous African USH cases investigated in this study, the majority of which (60%) were diagnosed clinically with Type 2 USH. All homozygotes shared a common haplotype. This mutation does not appear to cause nonsyndromic vision loss. CONCLUSIONS. Of interest is the origin of this common mutation relevant to the Bantu population migration into southern Africa. Further investigation of the phenotype may elucidate the disease biology, and perhaps reveal a larger cohort with the same mutation, with which to assess the impact of environmental and genetic modifiers and evaluate therapeutic trials.
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    Probing the mechanisms of action and resistance of mixed-ligand platinum(II) complexes with dual-stage antiplasmodium activity
    (2025) Ishmail, Fatima-Zahra; Chibale, Kelly; Wicht, Kathryn; Woodland, John; Egan, Timothy
    Malaria remains one of the largest parasitic disease burdens worldwide, with the vast majority of that burden occurring on the African continent. The ongoing high number of malaria cases and deaths is in part attributable to the emergence and spread of resistance to most clinical chemotherapeutics. With the reported development of partial resistance to the current front-line artemisinin-based combination therapies, there is an increased risk of malaria morbidity and mortality as limited replacement treatments are currently available. For that reason, it is essential to invest in the discovery of compounds with novel mechanisms of action (MoA), dual-stage activity, and with immutable targets. Until now, drug discovery has typically focused on the development of antimalarials that are entirely organic in composition. This has left the field of inorganic medicinal chemistry and transition metal-based chemotherapeutics underexplored and underrepresented.
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    (Re)storing and (Re)storying men with broken wrists: using intsomi as critical fabulation to refute the notion of queerness as un-African
    (2025) Nyezi, Freddy Junior Sikhanyiso; Mtshali, Mbongeni; Mbothwe, Mandla
    My research attempts to challenge the contemporary perception of homosexuality as “un-African”. This misconception is often grounded in the perceived absence of queer people of colour from the “archive” of black African (hi)stories that shape our collective understandings of who is and who is not properly “African”. Given that what we do know of how gender is conceived among African societies comes to us predominantly via the colonial archive with all its attendant elisions and lacunae, there is a strong case to be made for treating these histories and the authority they assume in defining our contemporary politics of belonging with some scepticism. Accordingly, I (re)turn to the archive of indigenous African folktales as a means to challenge cultural myths of queer black (un)belonging. In my final thesis project, I take the Xhosa ntsomi (folktale) seriously as a mode of producing and transmitting cultural knowledge and appropriate its formal aesthetics to create queer speculative fictions/myths that subvert neocolonial heteropatriarchy and the attempted erasure of black queer personhood from the story of Africa. Using the culturally embedded formal and narrative tropes of intsomi alongside techniques of biomythography and critical fabulations to queer the neocolonial archive, I work to “(re)store” and “(re)story” black queer African personhood, affirming its complicated place in African society and the visions of freedom and belonging animated by our shared histories of anti-/decolonial struggle.
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    The impact of early life exposures on lung function in African preschool children
    (2026) Chaya, Shaakira; Gray, Diane; Zar, Heather
    Respiratory disease substantially impacts global health in children with the highest burden in low- and middle-income countries (LMIC). Pneumonia is a leading cause of death in children under five years, while chronic respiratory disease is a major contributor to non-communicable disease burden across the life-course. Early lung function is crucial for respiratory health, with low lung function in childhood linked to higher risks of respiratory and cardiovascular disease and premature mortality later in life. Lung growth occurs rapidly from birth to school age, yet most cohort studies have measured lung function later in childhood or adulthood. Until recently, tools for measuring preschool lung function have been limited. Additionally, much of the available data comes from cohorts in high-income countries. Many factors known to be associated with poor respiratory health such as indoor air pollution (IAP), environmental tobacco smoke (ETS) and preterm birth are prevalent in LMIC. However, data on the early life impact on lung health in these settings are lacking. Emergent pulmonary function tests, feasible in preschool children, have the potential to fill this gap. This thesis aimed to investigate the determinants of preschool lung function in South African children enrolled in a birth cohort, the Drakenstein Child Health Study (DCHS). All 1143 children followed from birth who had infant lung function were included in the study, with lung function measured yearly between 3 to 5 years. Lung function measurements included tidal breathing, multiple breath washout and pre- and post-bronchodilator oscillometry and spirometry (from 5 years). At each visit, parents completed a questionnaire which assessed socioeconomic factors, smoking and exposure to passive cigarette smoke, current and past health history including lower respiratory tract infection (LRTI), HIV status and treatment history. Air pollutants were measured antenatally and at 4 to 6 months postnatally and included particulate matter 10, carbon monoxide, nitrogen dioxide, sulphur dioxide and volatile organic compounds. The chapters of the thesis cover: (1) A review of the need for and feasibility of lung function tools in preschool children, contributing to addressing the gap in our understanding of lung growth and development and its determinants during the preschool period. The results show that preschool lung function measurements are largely under-represented in LMIC, but feasible for clinical and epidemiological use, raising the potential of tracking lung function from early life through to adulthood and bridging the gap during the critical preschool period. The lack of suitable reference ranges for interpretation is highlighted, particularly for emergent preschool tests such as oscillometry. (2) Deriving the first reference equation for oscillometry in African children using a cohort of 690 healthy children between 3 and 17 years. (3) Investigation of the joint impact of antenatal and postnatal environmental exposures on lung development through to 3 years. These analyses show that both antenatal and postnatal IAP and ETS exposure impair lung function at 3 years. The effects of postnatal exposures on lung function were independent and additional to that of antenatal exposures, an important finding as these are modifiable factors. (4) The impact of preterm birth on lung function through 5 years, providing the first longitudinal description of lung function in preterm infant survivors in LMIC. The findings show that these children had impaired lung function trajectories over the first 5 years, notably in the moderate to late preterm group. LRTI and ETS were important modifiable factors contributing to reduced lung function in this vulnerable group. These finding have implications for clinical practice and public health, highlighting the need for improved maternal health initiatives to prevent preterm births, strengthen maternal pre-, peri- and postnatal health and to provide long-term follow-up of children born preterm. Additionally, the importance of educating healthcare professionals about the long-term effects of preterm birth is highlighted. In conclusion, preschool lung function testing was found to be feasible in a LMIC setting. The reference range equation contributed to developing the usefulness of this tool for African children. Major determinants of lung function included LRTI, ETS, and preterm birth. Public health initiatives to enhance maternal health and peri- and postnatal care, and strategies to reduce ETS and early-life LRTI such as novel preventive therapies, should be prioritised in LMIC settings.