Medical Science

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An investigation into kojic acid-associated mitochondrial toxicity and inflammation in melanoma cells (SK-MEL-1).
(2023) Suritham, Tamzin Kimera.; Chuturgoon, Anil Amichund.; Ghazi, Terisha.
ojic acid (KA), 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one, is used in agriculture, food, and cosmetics. KA is known to have antimicrobial, antifungal, antioxidant, and anti-inflammatory properties. The cosmetic industry's increasing interest in KA is due to its ability to inhibit tyrosinase activity resulting in skin lightening. The mitochondria play a key role in maintaining homeostasis and ensuring efficient melanin production. Therefore, mitochondrial dysfunction has severe effects on the skin. This study investigates mitochondrial stress, antioxidant responses, protein kinase signalling and inflammation in human melanoma (SK-MEL-1) cells. The mitochondria are important in processing metabolites and supplying the cell with energy in the form of ATP. KA interacts with key mitochondrial homeostasis proteins. Our results found an increase in macromolecule damage specifically lipid peroxidation and protein oxidation. Due to oxidative conditions, increased Nrf2 expression was observed. LON protease is ATP-dependent and regulated by Sirtuin 3 expression. Mitochondrial function was affected illustrated by decreased ATP production leading to decreased LON protease and Sirtuin 3 protein expression. Following increased oxidative stress, KA suppressed the expression of protein kinases but increased inflammatory mediators. There was decreased expression of phospho-Akt, Akt, phospho-GSK3β, p38 and ERK1/2. The mediation of the NLRP3 inflammasome involves priming and activation. At concentrations with high proliferation, NFκB gene and protein expression was activated. The protein kinase signalling pathways are known as mediators of inflammation; however, protein and gene expression of inflammatory mediators was increased following KA treatment. The inflammasome was subsequently activated as shown by an increase in intracellular caspase 1 levels as well as NLRP3, ILβ and IL-6 expression. KA induced mitochondrial stress and suppressed mitochondrial homeostasis proteins. The increased Nrf2 expression could have further downregulated LON protease expression and increased macromolecule damage. Oxidative conditions could have activated the inflammasome pathway independent of protein kinase signalling. In conclusion, KA displayed mitochondrial toxicity following acute exposure by suppressing mitochondrial homeostasis, protein kinase pathways and initiating inflammation. 1
Anatomic study of the morphologic relationship between the proximal left and right coronary arteries.
(2016) Singh, Sadhna.; Satyapal, Kapil Sewsaran.; Lazarus, Lelika.; Ajayi, Nasirudeen Oladipupo.
Arising from the aorta, the right (RCA) and left (LCA) coronary arteries provide the arterial supply to the heart. An extensive literature review revealed that most studies have either evaluated the morphology of the RCA or the LCA independently. This study aimed to document the relationship between the morphology of the RCA and LCA using coronary angiograms and fetal dissections. In addition, variations such as split or double RCA and absence of the LCA was documented. A review of 500 coronary angiograms and a fetal dissection of 41 heart specimens was conducted. The RCA and LCA were classified according to their branching patterns and arterial dominance. The embryologic relationship between the RCA and the LCA was also documented including their lengths and diameters. The angiographic review showed that the most prevalent branching pattern of the LCA was bifurcation in 65.8%, while trifurcation and quadrifurcation occurred in 20.4% and 1.6%, respectively. The splitting of the RCA and absence of the LCA occurred in 4.2% and 11.8%, respectively. A significant correlation was found between the split RCA and absent LCA showing that the split RCA was more prevalent in the absence of the LCA. The dissection of the fetal heart specimens (age range 13.13 - 26.95 weeks) found that the RCA arose from the right aortic sinus and provided arterial dominance in all the specimens. The LCA was classified into types according to their branching pattern. The bifurcation, trifurcation and quadrifurcation of the LCA occurred in 68.3%, 29.3% and 2.4% of hearts, respectively. The mean lengths of the RCA and LCA were 0.98 ± 0.54mm and 1.83 ± 0.77mm, respectively. The mean diameters of the RCA and LCA were 0.38 ± 0.12mm and 0.49 ± 0.17mm, respectively. A significant correlation was found between the RCA and LCA length and the fetal age indicating changes in the development of the coronary vasculature with fetal development. A knowledge of the distribution of the RCA and LCA assists in providing information on the area of the myocardium supplied. With the advent of coronary angiography, a comprehensive understanding of coronary arterial anatomy and their variations is necessary.
Anti-HIV and Immunomodulatory properties of the fractionated crude extracts isolated from Alternaria alternate.
(2024) Kubheka, Mbali Xolile.; Mkhwanazi, Nompumelelo Prudence.; Ndlovu, Sizwe Innocent.
Abstract available in PDF.
Antimicrobial susceptibility testing of four 5-nitroimidazoles against trichomonas vaginalis.
(2016) Mtshali, Andile.; Joubert, Bronwyn C.
Abstract available in PDF file.
Benign uterine conditions: correlating MRI and US findings: retrospective analysis of 33 patients.
(2016) Ramaema, Dibuseng Paulina.
Abstract not available.
The biological mechanisms associated with Depo-Provera and HIV-1 risk acquisition in women.
(2017) Takalani, Funanani.; Soliman, Mahmoud Elsayed Soliman.
Thirty-six years after the first identification of AIDS, the spread of its aetiological agents continues unabated, human immunodeficiency virus 1 (HIV-1) in particular. About 40% of HIV-1 infections have been reported to initiate in the female reproductive tract (FRT). However, the biological mechanisms through which these infections are spread are poorly understood hence there is now a major concern in women who use injectable hormonal contraceptives, particularly medroxyprogesterone acetate (MPA) administered as depot medroxyprogesterone acetate (DMPA) or Depo-Provera and an increase of HIV-1 risk acquisition. As per literature, the glucocorticoid receptor (GR) and progesterone receptor (PR) are the main targets for Depo-Provera in the FRT. Therefore, in this study we performed molecular dynamic (MD) simulation on both the GR and the PR systems in relation to DMPA as a way of validating their docking poses and binding energy trends. We also investigated the nature of their overall interaction themes using post-dynamic analysis and most importantly, we postulated possible biological mechanisms in which DMPA may act via the GR and the PR in association with increased risk of HIV-1 infection in women. Our findings revealed that, the effect of DMPA binding to both the GR and the PR could have a great impact on increased risk of HIV-1 infection in women. The reason being that when these receptors are activated by an agonist DMPA, they interact with a few residues in the ligand binding domain (LBD) which could affect the stability state of these receptors. They also interact with NFϰB transcription factor as well as the p300 coactivator in the nucleus to cause transactivation in the ectocervical (Ect1/E6E7) epithelial cell line of the FRT, in turn, increasing mRNA and protein secretion levels of proinflammatory cytokines.
Case series of subtotal exenteration with buccal mucosal graft for orbital squamous cell carcinoma.
(2016) Surajballi, Sharisha.; Kruse, Carl-Heinz.
The aim of the study was to look for a safe alternative to a disfiguring total orbital exenteration for orbital squamous cell carcinoma, so that a standard hospital issue inexpensive stock ocular prosthesis can be fitted with improved aesthetic results, rather than an expensive custom made prosthesis for the patient’s own cost. The subjects and methods involved a retrospective case review which was performed of patients from St Aidan’s Missionary Hospital initially, which was later amalgamated into the McCords Provincial Eye Hospital, Durban, KwaZulu-Natal, South Africa. Ten consecutive patients who underwent an ‘extended’ lid-sparing subtotal exenteration with minimally preserved healthy conjunctiva and a buccal mucosal graft were identified over a 3 year period from 1 January 2011 to 31 December 2013. Patients’ clinical records were reviewed. Results included all of the ten patients having a good aesthetic outcome at 4 weeks and six months with a standard hospital issue stock ocular prosthesis. One patient had a repeat buccal mucosal graft after forniceal shortening. Three patients had local recurrences within one year but all recurrences were identified easily and total exenteration was successfully performed. The survival rate at 3 years was ninety percent as one patient was lost to follow-up. A subtotal orbital exenteration with minimally preserved healthy conjunctiva and a buccal mucosal graft is cost effective, safe and cosmetically acceptable with a standard ocular prosthesis.
The changes in immune cells concentration during the progression of pre-diabetes to type 2 diabetes in a diet-induced pre-diabetic rat model.
(2019) Mzimela, Nomusa Christina.; Khathi, Andile.; Ngubane, Phikelelani Siphosethu.
T2D has been discovered to be preceded by a long-lasting condition known as prediabetes. The primary cause of prediabetes and T2D has also been shown to be continuous consumption of unhealthy diets and living a sedentary lifestyle. Type 2 diabetic patients have been discovered to have a supressed immune system, but it is still debatable whether immune activation begins at the pre-diabetes stage or during overt T2D. According to literature, T2D is a result of elevated levels of glucose known as hyperglycaemia caused by a condition called insulin resistance. Additionally, T2D has also been shown to be characterised by increased levels of triglycerides, low density lipoproteins (LDL) and decreased levels of high-density lipoproteins (HDL). Insulin resistance then causes metabolic and signalling pathways such as oxidative stress, activation of PKC pathway, formation of advanced glycation end products (AGEs) and shunting of polyol pathway which trigger metabolic inflammation resulting in a dysregulated innate immunity. Dysregulated innate immunity in T2D patients has also been discovered to be due immune response caused by hyperglycaemia. However, it has not been discovered if immune activation occurs at the pre-diabetes stage. It has not been discovered if upregulation of inflammatory markers occurs at prediabetes stage. This study envisaged to characterise the changes that occur in immune cell concentration during the progression of pre-diabetic stage and if there is upregulation of inflammatory markers such as fibrinogen, CRP, CD40L, p-selectin, IL-6 and TNF-α during pre-diabetic stage. To accomplish this, male Sprague Dawley rats were divided into two groups. The first group was fed a high-fat high-carbohydrate diet for 20 weeks to induce pre-diabetes and the second group was fed a normal rat diet for 20 weeks. To confirm if the animals were pre-diabetic, criteria according to American Diabetes Association were used. The animals were then divided into 2 groups which is the pre-diabetic group with 6 animals and a non-diabetic control with another 6 animals. The animals were then further monitored for another 12 weeks (experimental period) while fed the same diet. Blood was collected for haemocytometer analysis on week 0,4,8 and 12 of the experimental periods after which the animals were sacrificed. Plasma was collected from centrifuged blood for ELISA (TNF- α, CRP, P-selectin, CD40 L, fibrinogen & IL-6). Adipose tissue was collected for histology. The results showed a significant decrease in blood percentage count of neutrophils and eosinophils at week 12 experimental period and these immune cells were further observed embedded in-between the adipocytes of adipose tissue. This indicated that neutrophils and eosinophils are produced due to hyperglycaemia and then recruited to the inflamed area such as adipose tissue. The blood percentage count of lymphocytes, basophils and monocytes showed a significant increase at week 12, indicating their increase in production in the bone marrow during immune response. Additionally, the results showed a significant increase in inflammatory cytokines such as TNF-α, IL-6, CRP and P-selectin. The results also showed a slight increase in inflammatory markers such as CD40L and fibrinogen. These finding indicate that there is immune activation during pre-diabetes stage due to changes in immune cells concentration and upregulation of inflammatory markers.
Characterization of Candida isolates from South African pregnant and non-pregnant women.
(2023) Sukali, Gloria.; Abbai, Nathlee Samantha.; Mabaso, Nonkululeko.
Candida infections are a serious health threat to women. Characterization of Candida isolates has become the gold standard method used in determining antimicrobial susceptibility profiles and resistance mechanisms in vaginal Candida infections. However, there is a lack of data on the antimicrobial susceptibility profiles of South African Candida isolates to amphotericin B. This study investigated antimicrobial resistance profiles and genotypes of Candida isolated from South African pregnant and non-pregnant women. This study was a sub-study of a larger study which involved the diagnosis of vaginitis and vaginosis pathogens in women. For the parent study, n=150 women were recruited from the King Edward VIII hospital in Durban, KwaZulu-Natal, South Africa. The women enrolled in the parent study were; 18 years and older, were willing to provide written informed consent and were willing to provide self-collected vaginal swabs. A total of 72 Candida isolates were obtained by culture. Of the 72 isolates, 31 isolates were obtained from pregnant women and 41 isolates were from non-pregnant women. The isolates were typed using the ABC genotyping method. Susceptibility testing was performed using the broth microdilution assay to measure the minimal inhibitory concentrations (MICs) for clinical isolates to amphotericin B. The Candida albicans ATCC 10231 strain was used as a control strain, and untreated cultures of the respective isolates were used as growth controls. Descriptive characteristics of the study participants according to Candida status were presented as frequencies and percentages. Comparisons by Candida status in the descriptive characteristics were performed using Chi square tests with a 5% significance level. P-values ≤0.05 were considered significant. All analyses were conducted using STATA. The prevalence of Candida in the study population was 48.0% (72/150). All the isolates (100%) were confirmed to be C. albicans as per the germ tube test and quantitative polymerase chain reaction (PCR) using primers and probes specific for C. albicans. All 72 isolates (100%) produced positive PCR results for C. albicans. The majority of the isolates (45/72; 62.5%) yielded a 450bp band which was assigned Genotype A. Of the 72 isolates, 19 isolates (26.4%) yielded a band size of 840bp and was assigned Genotype B. A total of 11.1% (8/72) of the isolates yielded band sizes of 450bp and 840bp which was Genotype C. Of the 72 isolates tested, 79.2% (57/72) of the isolates were resistant to amphotericin B (MIC >1ug/ml) and 20.8% (15/72) of the isolates were susceptible to amphotericin B (MIC ≤ 1 ug/ml). When linking MIC patterns to distribution of genotypes, it was observed that the majority (80%) of the isolates which were assigned genotype A were resistant to amphotericin B. When linking clinical symptoms with the distribution of genotypes, it was observed that the majority (58.8%) of women who reported having current symptoms of abnormal vaginal discharge carried genotype A. Genotype A was most prevalent in women who had been treated for vaginal infections in the past and in women who were HIV positive with prevalence of 64.1% and 60.8%, respectively. genotype A was most prevalent in the non-pregnant women with a prevalence of 63.4%. Genotype A was prevalent (61.3%) amongst the pregnant women and the majority (66.7%) of the HIV negative women had Candida infections which belonged to genotype A. The prevalence of Candida was shown to be high in both pregnant and non-pregnant women in this study. This study also found a high level of resistance to the antifungal amphotericin B. Currently in our local setting, resistance patterns to the commonly used antifungals to treat Candida infections are not being monitored. There is a need for antifungal resistance monitoring in order to reduce the risk of future persistent and untreatable infections.
A comparative chemistry of coa® herbal medicine and herbal extracts of Vernonia Amygdalina (Bitter leaf) and Persea Americana (Avocado).
(2018) Boadu, Akwasi; Nlooto, Manimbulu.
The aim of this study is to investigate the phytochemical compounds present in standard COA®, dichloromethane (DCM), ethanol (EtOH), hexane (HEX), and ethyl acetate (EtOAc) , extracts of COA® compared to leaf extracts of Vernonia amygdalina and Persea americana collected from Cape Coast (Ghana) and Durban (South Africa) by phytochemical screening techniques and gas chromatography-mass spectrometry (GC-MS) analysis. Findings from this study revealed that leaf extracts of P. americana and V. amygdalina have been used in many local African communities for management of various diseases. Ethnomedicinal use and pharmacological properties of leaf extracts of P. americana andV. amygdalina may justify polyherbal formulation involving the two plants in the treatment of diseases such as diabetes, hypertension and other diseases. Outcomes of the preliminary phytochemicals screening showed the presence of alkaloids, anthraquinones, saponins, flavonoids, tannins, terpenoids and glucosides in ethanolic leaf extracts and standard COA®. GC-MS study of standard COA®, COA® extract and leaf extracts of P. americana and V. amygdalina collected from Ghana and South Africa had 60y phytochemical compounds identified in the hexane extract of COA® extract, 47 in DCM, 37 in ethyl acetate, 18in ethanol and 11 in standard COA® herbal medicine. The identification of phytochemical compounds and pharmacological actions was based on the name of the chemical compound, retention time and molecular formula from GC-MS analysis. The major phytochemicals common to COA® extract and leaf extracts of P. americana and V. amygdalina were heneicosane, phytyl acetate, pyrene, octadecanoic acid, eicosane, 2-methyltetracosane, pentadecanoic acid, hexadecanamide, and octadecanamide. Most of these major phytochemicals are present in ethanolic extracts of both COA® and leaf extracts of P. americana and V. amygdalina Leaf extracts of P. americana and V. amygdalina collected from Ghana have more phytochemicals compared to that of South Africa. The finding, of this study, confirm the presence of P. americana and V. amygdalina leaf extracts in COA® herbal medicine. It also confirms the profound variations in phytochemicals of P. americana and V. amygdalina leaf extracts due to the effects of environmental factors and geographical locations.
Computational studies of mycobacterium tuberculosis L, d-transpeptidase2.
(2018) Ntombela, Thandokuhle.; Honarparvar, Bahareh.; Kruger, Hendrik Gerhardus.; Maguire, Glenn Eamonn Mitchel.
Tuberculosis (TB) is still one of the most highly elusive lethal transmittable diseases to eradicate and persist to be a major threat to public health due to emergence of drug resistance. Drug-resistant is steadily increasing worldwide, therefore, there is an urgent need for development of improved efficacious antibiotics and novel drug targets to successfully contain the disease. Peptidoglycan layer (PG) is the major attribute in bacterial cell envelope and is essential for protection and growth in all bacterial species including Mycobacterium tuberculosis(Mtb). The biosynthesis pathway for PG is extremely intricate and involves numerous interconnected metabolites such as N-acetylmuramic(NAM) acid and N-acetylglucosamine(NAG), that are required during transpeptidation. These two sugar molecules are linked together by a β (1-4) glycosidic bond and the NAM attaches 3-5 amino acid peptide stems. Consequently, the peptidoglycan strands are cross linked by transpeptidases, namely D, D- and L, D-transpeptidases, forming crucial 4→3 and 3→3 cross-linkages respectively. Both D, D- and L, D-transpeptidases need to be inhibited concomitantly to eradicate the bacterium. L, D-transpeptidase 2 (LdtMt2) is one of the paralogs that is essential for Mtb growth, cell morphology and virulence during the chronic stage of the disease. This paralog has major influence in drug resistance and persistence of tuberculosis. The traditional β-lactam family of antibiotics have been reported to be effective against Mtb following the inactivation of β-lactamases (BlaC) known to rapidly hydrolyze the core β-lactam ring. The classic penicillins inhibit D, D-transpeptidases, while L, D transpeptidases are blocked by carbapenems. Despite several studies in this field, to the best of our knowledge, limited attention has been paid to the inhibition mechanism of LdtMt2 using carbapenem derivatives. In this regard, we need to explore reliable alternative strategies that are most cost-effective in terms of investigating the interactions of FDA approved carbapenems against Mtb L, D-Transpeptidases and study the role of explicit water molecule confined in the active site. As a result, computational chemistry has provided the possibility to sightsee and investigate this problem with relatively cost effective computational techniques. In this thesis, we applied a hybrid quantum mechanics and molecular mechanics techniques (QM:MM), Our own N-layered Integrated molecular Orbital and Molecular Mechanics (ONIOM) approach, to investigate the binding interaction energies of carbapenems (biapenem, imipenem, meropenem and tebipenem) against L, D-transpeptidase 2. Furthermore, the role of explicit water molecule confined in the active site was also explored using the same hybrid method to ascertain the nature of binding interaction energies of carbapenems against LdtMt2. In all the investigated carbapenem─LdtMt2 complexes, the carbapenems and the catalytic active site residues of LdtMt2 (Cys205, His187, Ser188, His203 and Asn207) were treated at QM (B3LYP/6-31+G(d)) level of theory whereas the remaining part of the complexes were treated at MM level (AMBER force field). The explicit water molecules near the carbapenems were considered and treated at QM as well. The obtained findings of Gibbs free energy (G), enthalpy (H) and entropy (S) for all studied complexes showed that the carbapenems exhibit reasonable binding interactions towards LdtMt2. This can be attributed by the structural dissimilarities of the carbapenems side chain which significantly induce conformational changes in the LdtMt2. In comparison, the binding free energy calculations of the model system with explicit water molecule yielded significant binding interaction energies. The QTAIM and NBO results confirmed the nature of binding free energies that the topological properties of atoms in molecules and the delocalization of electrons are from a bonding to antibonding orbitals in hydrogen bond interactions and this has enhanced the stability of carbapenem―LdtMt2 complexes. We believe that molecular insight of the carbapenems binding to LdtMt2 and the role of explicit solvent will enable us to understand the inhibition mechanisms.
Computational studies of pentacycloundecane peptide based HIV-1 protease inhibitors.
(2013) Chibi, Buyisile.; Soliman, Mahmoud Elsayed Soliman.; Kruger, Hendrik Gerhardus.; Govender, Thavendran.; Maguire, Glenn Eamonn Mitchel.
Abstract available in PDF.
Defining current facial fracture patterns in a quaternary institution following high-velocity blunt trauma.
(2016) Magagula, Senzwesihle Clive.
Background: In the early 20th century, René Le Fort studied facial fractures resulting from blunt trauma and devised a classification system still in common use today. This classification, however, was based on low-velocity trauma. In modern practice, in a quaternary-level referral hospital, patients are often admitted following high-velocity injuries that mostly result from motor vehicle collisions. Objectives: A retrospective study to define facial bone fractures occurring subsequent to highvelocity trauma. Method: A retrospective study comprising the review of CT scans of 52 patients with highvelocity facial fractures was performed between April 2007 and March 2013. Injuries were classified using the Le Fort classification system. Deviations from the true Le Fort types, which are often depicted in the literature as occurring bilaterally and symmetrically, were documented; these included unilaterality, occurrence of several Le Fort fractures on one side of the face, occurrence of several Le Fort fractures on different levels and on different sides of the face, and occurrence of other fractures in addition to Le Fort fractures. Results: Of the 52 cases, 12 (23%) had Le Fort injuries, with true Le Fort fractures occurring in only 1, and 11 deviating from the classic description. Nine patients had Le Fort fractures and additional fractures. Mandibular and zygomatic bone fractures were found to be common associations with Le Fort injuries, occurring in 58% and 33% of the cases respectively. Conclusion: Fractures occurring in modern practice often deviate from the traditional Le Fort classification. Precise recognition of these deviations and recognition of additional associated fractures is pivotal in their management, assisting the surgeon in determining the treatment plan, such as the surgical approach and the order in which to fix the various fractured components.
Deoxynivalenol downregulates NRF2-induced cytoprotective response in human hepatocellular carcinoma (HepG2) cells.
(2017) Ndlovu, Siqiniseko Sinikiwe.; Chuturgoon, Anil Amichund.; Nagiah, Savania.
Deoxynivalenol (DON) is a mycotoxin produced by Fusarium species that commonly infect agricultural foods. DON exhibits multiple toxic effects in both animals and humans, binding to the A site of the 28S ribosome and inhibits peptidyl transferase and protein elongation. It induces cytotoxicity through oxidative stress and inhibition of protein synthesis. Liver cells possess the antioxidant signalling mediator - Nuclear erythroid-2-Related factor (NRF2) that is activated in response to oxidative stress. There is no sufficient work done to show if the HepG2cells have an ability to withstand the molecular modifications induced by DON. The aim of the study was to investigate the cytotoxicity of DON and its effect on the NRF2 antioxidant response in HepG2 cells. The MTT assay was used to determine a dose response of DON (72 hr) on cell viability and to generate an IC50 value to use in subsequent assays. The intracellular concentration of GSH and ATP was determined using Luminometry. Lipid peroxidation and membrane damage were assessed by TBARS and LDH cytotoxicity assays respectively. Protein expression of NRF2, phosphorylated (p-)NRF2, catalase (CAT), superoxide dismutase (SOD)2, and Sirtuin (Sirt)3 was quantified by Western Blotting. The mRNA expressions of GPx, CAT and SOD2 were quantified using qPCR. DON decreased cell viability in a dose-dependent manner with an IC50 value of 26.17 μM. DON caused a significant decrease in the intracellular GSH concentration (1.77-fold, p= 0.0005). There was a significant decrease in the intracellular ATP content (1.92-fold, p= 0.0002).The study shows an induced lipid peroxidation and membrane damage in HepG2 cells by DON, as there was a significant increase in extracellular levels of both MDA (1.89-fold, p=0.0020) and LDH (1.35-fold, p=0.0207). DON reduced total NRF2 expression (0.30-fold, p= 0.0017), however activated p-NRF2 was significantly up-regulated (3.54-fold, p= 0.0085). There was a downregulation in the NRF2 target antioxidant proteins: CAT (0.33-fold, p= 0.005) with a concomitant decrease in CAT mRNA levels (0.02-fold, p= 0.0003), SOD2 (0.02-fold, p= 0.0137), with a parallel trend in the levels of SOD2 mRNA (0.06-fold, p= 0.0020) by DON. This toxin also significantly decreased the mRNA expression of GPx levels (0.03-fold, p= 0.0006). The expression of a mitochondrial stress response Sirt3 was significantly decreased (0.14-fold, p= 0.0058). Taken together, the data shows that DON causes oxidative stress and downregulates the NRF2-induced cytoprotection in HepG2 cells. Keywords: Deoxynivalenol Antioxidant response NRF-2
Drug susceptibility testing of second and third line anti-tuberculosis drugs used in the management of extensively drug resistant tuberculosis.
(2013) Moodley, Salona.; Moodley, Prashini.
Drug resistant tuberculosis is a major contributor to South Africa’s quadruple burden of disease. Management of this infection in a highly HIV endemic area is a constant challenge. There is a paucity of new anti-tuberculosis agents in the developmental and clinical trial phases to address the problem of extensively-drug resistant tuberculosis (XDR-TB). In an attempt to affect a cure in patients with XDR-TB, it has become necessary to re-introduce previously used anti-tuberculosis drugs, as well as antimicrobial agents designed for treatment of non-tuberculosis infections. Whilst these drugs may have previously been tested and shown efficacy in drug susceptible tuberculosis, their activity in XDR TB strains was not tested before introduction for management of XDR-TB in KwaZulu-Natal, South Africa. Drug susceptibility testing (DST) plays an integral role in the diagnosis and treatment options for tuberculosis. It is able to decrease the burden and spread of resistant tuberculosis. However DSTs methods for second line anti –TB drugs (SLDs) and third line anti-TB drugs (TLDs) have not been standardised. Critical concentrations of these anti-TB drugs remain unknown or vary within and between settings thus further hampering the control of TB.
Drug transporter expression and genetic polymorphisms in HIV endemic settings.
(2023) Zondo, Nomusa Margaret.; Archary, Derseree.; Sobia, Parveen.
Abstract available in a PDF.
The effects of rhoicissus tridentate dichloromethane extract and its bioactive compounds on uterotonic and glucose lowering activity in-vitro.
(2019) Mvelase, Zinhle Priscilla.; Mabandla, Musa Vuyisile.
Poor myometrial contractility during labour is associated with an extended partuition process that can affect the neonate’s health status. Chronic use of conventional treatments for diabetes mellitus is sometimes associated with undesirable effects. In an effort to overcome these challenges, we explored the ability of a crude medicinal plant extract of Rhoicissus tridentate (RT) and its bioactive compounds, beta-sitesterol (BS) and arjunolic acid (AA) to act as a multi-target agent to manage both poor myometrium contractility and diabetes mellitus. We thus investigated the uterotonic effects of RT and its bioactive ingredients BS and AA using uterine strips in-vitro. Further we studied the glucose lowering effects and possible mechanisms of action of RT and its bioactive compounds using muscle (C2C12) and liver (Chang) cell lines.For uterotonic studies, diethylstilboestrol-treated female Sprague-Dawley rats were sacrificed by decapitation and 2-3 cm of the uterine muscle was isolated and suspended in an organ bath containing aerated de Jalon’s buffer maintained at 32 ºC. Each muscle strip was treated with graded concentrations of RT (0.24-62.08 mg/mL) or BS (0.09-57.10 μmol/mL) or AA (0.37-22.80 μmol/mL). Rhythmic contractions in myometrial tissue incubated in the absence of plant extract or oxytocin served as the absolute control. To determine the synergistic effect of RT and its bioactive ingredients, the uterine strips were pre-treated with oxytocin (1.11 nmol/mL) before being treated with various concentrations of RT, BS or AA. Afterwards, the force and rate of contractions were recorded. Thereafter, the uterine strips were harvested for prostaglandin F2 alpha (PGF2α) and oxytocin-receptor concentration measurements. In experiment 2, we assessed the effects of RT/BS/AA on glucose metabolism. Liver (Chang) and muscle (C2C12) cell lines were cultured in Eagle’s Minimal Essential Medium and Dulbecco’s Modified Eagle’s Medium, respectively. To initiate glucose utilization experiments, separate preparations of muscle and liver cell lines were incubated at 37 ºC in a humidified incubator with 5% CO2 with the following concentrations of each compound, 12.5, 25 and 50 μg/ml. Both the liver and muscle cell lines were challenged with 19 mmol and 29 mmol of glucose respectively. Cells incubated in DMSO (0.1%), insulin (40 μg/mL) or metformin (16 μg/ml) served as untreated and treated positive controls. Media glucose concentration and cell viability were measured at 0, 12, 24 and 48 hour post incubation. Thereafter, cells were assessed for glycogen, GLUT 4 and glycogen synthase while the media harvested was assessed for Alanine amino transferase (ALT) and aspartate amino transferase (AST) activity. Our results showed an increase in the force and rate of uterine muscle contraction following treatment with RT, BS and AA (p<0.05). While co-treatment of RT/BS with oxytocin had a synergistic effect on force and rate of myometrium contractility, RT treatment resulted in decreased PGF2α and oxytocin receptor concentration. Treatment with BS/AA resulted in an increase in PGF2α receptor concentration, (p<0.05) but a decrease in oxytocin receptors. RT/BS and oxytocin resulted in increased PGF2α and oxytocin receptor concentration. The administration of RT/BS/AA did not result in cell toxicity in both cell lines. The individual treatments of RT and BS resulted in decreased ``media glucose concentration with concomitant increases in glycogen concentration after 48 hours in both cell lines. The increased GLUT4 concentration in muscle cell lines following treatment RT or BS supported this. Furthermore, RT administration resulted in increased glycogen synthase concentration in both cell lines. The observations suggest that RT promotes uterine muscle contractility and glucose disposal in the liver and skeletal muscle cell lines. This may suggest that RT and its associated bioactive compounds may be of benefit in alleviating poor myometrium contractility and diabetes-associated hyperglycaemia with BS playing a more active role than AA.
Evaluation of teixobactin derivatives as potential antimicrobial agents.
(2017) Ramchuran, Estelle Juanita.; Bester, Linda Antionette.
Methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus (VRE) are on the World Health Organization (WHO) high priority list of pathogens that require serious attention. Therefore, the need for novel class of compounds is vital in overcoming this problem. Teixobactin is a new class of antibiotic that has exhibited antimicrobial activity against resistant bacteria. In this study we are expanding the investigation of teixobactin derivatives against clinically relevant bacterial isolates from South African patients. The minimum inhibitory concentration (MIC), the minimal bactericidal concentration (MBC), the serum effect on the MIC’s and the time kill kinetics studies of three of our synthesized teixobactin derivatives 3, 4 and 5 were ascertained by broth microdilution according to the CLSI 2017 guidelines. Haemolysis on red blood cells (RBCs) and cytotoxicity on peripheral blood mononuclear cells (PBMCs) were performed to investigate the safety of these derivatives. MIC’s of the teixobactin derivatives against ATCC reference strains were between 4-64 µg/ml (3), 2-64 µg/ml (4) and 0.5-64 µg/ml (5). The MIC’s for MRSA were 32 µg/ml for (3), 2-4 µg/ml for (4) and 2-4 µg/ml for (5) whilst the MIC’s obtained for VRE’s were 8-16 μg/ml for (3), 4 μg/ml for (4) and 2-16 μg/ml for (5). 50% human serum had no effect on the MIC’s. All these derivatives did not show any effect on cell viability at their effective concentration. Teixobactin derivatives (3, 4 and 5) were capable of inhibiting bacterial growth in drug resistant bacteria and thus serve as potential antimicrobial agents.
Evaluation of the Alere Afinion™ AS100 for measuring the levels of C-Reactive Protein in an aged population.
(2020) Mpofana, Innocentia Baxolile.; Abbai, Nathlee Samantha.; Nyirenda, Makandwe.
Introduction The Alere Afinion™ AS100 analyser is a compact bench-top, multi-assay, point-of-care (POC) analyser that provides valuable near patient testing at the point of care. It utilises the latest technology to measure C-Reactive Protein and other analytes to monitor patients’ disease progression. The main objective of the study was to evaluate the performance of the Alere Afinion™ AS100 analyser compared with a reference laboratory test method, ABX Pentra 400 for the measurement of C-Reactive Protein (CRP). Methods This study was a retrospective analysis in which stored serum samples obtained from a cross-sectional study referred to as Sexual Health, HIV infection and comorbidity with non-communicable diseases among Older Persons (SHIOP) were tested for the quantification of the CRP. The primary aim of SHIOP was to describe sexuality, sexual health and the comorbidity of HIV and sexually transmitted infections with chronic non-communicable diseases in adults aged ≥50 years in a setting of high HIV prevalence. Serum stored at -20 ⁰C from participants that consented to long term storage(n=183) was used to perform this evaluation. The serum samples were used to measure CRP on the Alere Afinion™ AS100 and ABX Pentra 400, respectively. Lin’s correlation coefficient was used to assess the agreement between the two analysers for the measurement of CRP. Risk factors associated with elevated CRP levels were assessed through this study. Results A total of 183 serum samples were tested in the study. The mean age of the study participants was 7.62 years (SD 8.15). Male participants were slightly older than female participants (61 vs 58years, p<0.05). Approximately 14.2% of study participants were above 70 years of age. The study population consisted of 77/183 (42%) Black South Africans and 106/183 (57.9%) Indians. The Alere Afinion™ AS100 was able to correctly classify (165/183) >90% of the CRP results when compared to the ABX Pentra 400. Bland-Altman analysis and linear regression analysis showed an excellent agreement (correlation concordance 0.97) between the two analysers. This study showed that being obese (Odds Ratio [OR]: 1.98, 95% Confidence Interval [CI]: 1.3616, 2.889, p<0.001) and having low HDL levels (OR: 1.64, 95% CI: 1.158, 2.307, p= 0.005) were the only significant risk factors that were associated with elevated CRP levels. Conclusion This study showed that the Alere Afinion™ AS100 can be used for the measurement of CRP in instances where CRP is greater than 5mg/L and this may enhance the process of patient care and management in low resource settings. Keywords: C-Reactive Protein (CRP), Affinion AS100, Sexual Health, HIV infection and comorbidity with non-communicable diseases among Older Persons (SHIOP), ABX Pentra 400.
Evaluation of the left ventricular ejection fraction post right ventricular pacing at Inkosi Albert Luthuli Central Hospital (IALCH), Durban, KwaZulu-Natal (KZN).
(2016) Kasipersad, Sherlina.; Magula, Nombulelo Princess.
Since the implantation of the first artificial pacemaker in 1958, these devices have become the treatment of choice in bradycardias. Despite its widespread use, only a few studies have looked at the effects of single chamber right ventricular(RV) pacing on left ventricular(LV) function in patients with sinus node dysfunction or atrioventricular node dysfunction. In addition, these studies have produced conflicting results with no consensus reached. Furthermore, the limitation to these studies were the small sample sizes and the absence of sequential echocardiographic monitoring of LV function in each patient. To the best of the authors’ knowledge, no such studies have been conducted in South Africa. This study reviewed data collected from Inkosi Albert Luthuli Central Hospital (IALCH), which is a government hospital in Durban, KwaZulu-Natal (KZN), South Africa. The objective of the study was to evaluate the effects of RV pacing on LV function in a setting where the majority of patients requiring a permanent pacemaker receive single chamber RV apical pacing. The focus of this study was to assess the effect of RV pacing on LV function by assessing the ejection fraction(EF), on echocardiography, pre and post pacemaker insertion. A retrospective chart review of 465 patients managed at the IALCH pacemaker clinic from 2003 up to 2012 was undertaken. Adult patients 18 years and older with a documented EF at the time of insertion of a pacemaker were included in the study. Patients were excluded from the study if they had coronary artery disease (CAD), unrepaired valvular heart disease, atrial fibrillation or dual chamber pacemakers. After enforcing the exclusion criteria, 430 patients were excluded and only 35 patients were eligible for the study. LV dysfunction was pre-defined as a left ventricular ejection fraction (LVEF) of < 50%. This study showed that RV pacing did not have a statistically significant effect on LV function post pacemaker insertion, based on the assessment of EF. The study was limited by the low number of eligible patients as it was a retrospective study and obtaining data was difficult as most patients who require a pacemaker do not routinely have a baseline echocardiograph done prior to insertion of the pacemaker. Another limiting factor in the study was that EF was the only modality of LV function that was assessed. Moreover, evaluation of the EF on echocardiography is subjective and user dependent. International studies have shown that the site of RV pacing has an impact on the degree of LV dyssynchrony and function. This factor could not be assessed in the current study as the site of RV pacing was not documented and was not standardised. Pacing in the correct clinical context is a necessity and is lifesaving. Current literature shows that RV pacing is a safe, relatively simple, convenient procedure that is well tolerated and is effective. This study showed no deterioration in LV function in patients post RV pacemaker insertion, which is important as the RV remains the most common site of lead placement especially in the resource limited state sector. Some studies have reported that RV pacing is associated with LV dysfunction. However, since there is a paucity of level 1 evidence regarding this aspect of RV pacing, the need for prospective studies on the long-term effects of RV pacing on LV function is required. In addition, the impact of alternative pacing sites on LV function should be explored.

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