Research

School of LMMS


Researcher: Ms Nikita Naicker

Designation: PhD study

Study: Trigonella foenum-graecum seed extract, 4-hydroxyisoleucine and metformin stimulate proximal insulin signaling and increases expression of glycogenic enzymes and GLUT2 in HepG2 cells

Summary: Fenugreek (Trigonella foenum-graecum) is globally recognized for its medicinal properties and hypoglycaemic effects. The seed extract as well as its active compound, 4-hydroxyisoleucine (4-OH-lle), have been shown to reduce hyperglycaemia insulin resistance. The mechanism by which this occurs has not been investigated in human liver cells (HepG2) in comparison to the anti-hyperglycaemic drug, metformin. We investigated the effect of fenugreek aqueous seed extract (FSE), 4-OH-lle and metformin in human hepatoma HepG2 cells relative to insulin as a positive control. Cells were treated with FSE and 4-OH-lle at 10ng/ml and 100ng/ml under normoglycaemic (5mM glucose) and hyperglycaemic (30mM glucose) conditions for 72h. Tyrosine phosphorylation of insulin receptor-β (IR-β), protein kinase B (Akt) and glycogen synthase kinase-3α/β (GSK-3α/β) was determined by western blotting. Gene expression of sterol regulatory element binding protein 1c (SREBP1c), glucose transporter 2 (GLUT2), glycogen synthase (GS) and glucokinase (GK) was evaluated by qPCR and supernatant glucose levels were measured using the Picollo Biochemistry Analyser. Under normo- and hyperglycaemic conditions, FSE, 4-OH-lle, insulin (100ng/ml) and metformin (2mM) caused a significant increase in tyrosine phosphorylation of IR-β, Akt and GSK-3α/β. Glucose uptake, however, was most significantly increased in FSE treated cells during normo-and hyperglycaemic conditions. FSE induced the most significant changes in downstream insulin signaling, GS, GK, SREBP1c and GLUT2 expression as compared to 4-OH-lle, metformin and insulin. Also, FSE significantly increased glucose uptake. Collectively, these findings provide a mechanism by which FSE exerts anti-hyperglycaemic effects similar to metformin and insulin occurs via enhanced insulin signaling, gene expression and increasing glucose uptake.

 


Researcher: Ms Ayanda Khumalo

Designation: Masters Research

Study: Immunoexpression of Uterine Natural Killer Cells in HIV-Associated Pre-Eclamptic and Normotensive Pregnancies

Researcher: Ms Lihle Qulu

Designation: PhD study

Study: Exposure to prenatal stress has deleterious effects on hippocampal function in a febrile seizure rat model

Summary: Prenatal stress has been shown Q2 to result in the development of a number of neurological disorders in the offspring. Most of these disorders are a result of an altered HPA axis resulting in higher than normal glucocorticoid levels in the affected neonate. This leaves the offspring prone to immune challenges. Therefore the aim of the present study was to investigate the effects of prenatal stress and febrile seizures on behavior and hippocampal function. Pregnant dams were exposed to restraint stress during the third trimester. Following birth, febrile seizures were induced in two week old pups using lipopolysacchar-ide and kainic acid. A week later, anxiety-like behavior and navigational ability was assessed. Trunk blood was used to measure basal corticosterone concentration and hippocampal tissue was collected and analyzed. Our results show that exposure to prenatal stress increased basal corticosterone concentration. Exposure to prenatal stress exacerbated anxiety-like behavior and impaired the rat's navigational ability. Exposure to prenatal stress resulted in reduced hippocampal mass that was exacerbated by febrile seizures. However, exposure to febrile seizures did not affect hippocampal mass in the absence of prenatal stress. This suggests that febrile seizures are exacerbated by exposure to early life stressors and this may lead to the development of neurological symptoms associated with a malfunctioning hippocampus.

Researcher: Ms Lihle Qulu

Designation: PhD study

Study: Searsia chirindensis reverses the potentiating effect of prenatal stresson the development of febrile seizures and decreased plasmainterleukin-1 _ levels

Summary: It is estimated that more than 80% of patients with epilepsy live in developing countries with 50–60% ofthem being children. This high prevalence is perpetuated by low socio-economic challenges, poor healthcare facilities and lack of drug affordability. Searsia chirindensis formerly known as rhus chirindensis andcommonly known as ‘Red Current’ is a popular traditional medicinal plant, which has been used to treata number of illnesses such as heart complaints and neurological disorders. The aim of this study is toinvestigate the effects of S. chirindensis on the development of febrile seizure in a prenatally stressed rat.Febrile seizures were induced by administering lipopolysaccharide to 14-day-old rat pups followed bykainic acid. A subset of the rats was treated with Searsia after induction of febrile seizures. Interleukin-1 _ (IL-1 _) levels were measured in plasma. Lipid peroxidation was determined in liver tissue. Our datashows that treatment with Searsia reduced interleukin-1 _ levels in plasma of the febrile seizure rats andprevented lipid oxidation in the liver. Prenatal stress is dampened by the beneficial effects of Searsia onseizure development in rat pups. These results highlight the potentiating effects of Searsia in the reversalof febrile seizures and prenatal stress effects.

Researcher: Sadiyah Cassim, Lihle Qulu, Musa V Mabandla

Designation: Human Physiology academics

Study: Prenatal stress and early life febrile convulsions compromise hippocampal genes MeCP2/REST...

Summary: Early life neuronal insults exacerbate the development of febrile seizures and can result in epigenetic changes in the hippocampus. The MeCP2 and REST genes play a pivotal role in cognition as both contribute to neuronal function. In this study, cognitive function and expression of the MeCP2 and REST genes in the hippocampus were investigated in four groups of Sprague Dawley rats offspring viz. (1) Normally reared treated with saline (NSS). (2) Prenatally stressed treated with saline (SS). (3) Normally reared with febrile seizures (NSFS). (4) Prenatally stressed with febrile seizures (SFS). Pregnant dams were subjected to 1h of restraint stress for 7days starting on gestational day 14. Following birth, a once-off exposure to saline injections or febrile seizure induction was conducted on postnatal day (PND) 14. Behavioural tests were conducted using the Morris-Water maze on PND 21 and 30. Our results showed a febrile seizure effect on learning and memory in the non-stressed animals. However, febrile seizures did not exacerbate learning deficits in the prenatally stressed animals. Gene analysis found a down-regulation in MeCP2 gene expression and an up-regulation of the REST gene in prenatally stressed animals. Exposure to febrile seizure resulted in down-regulation of both MeCP2 and REST gene expression in the non-stressed animals, but febrile seizures did not exacerbate the stress effect on gene expression. This suggests that exposure to prenatal stress (SS) and febrile seizures (NSFS) may impair cognitive behavioural function. However, in the NSFS animals, there seems to be an attempt to counteract the effects of febrile seizures with time.

 

Researcher: Dr Zaza Ndlovu

Designation: HPP academic

Study: Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impacts Viral Set Point, was conducted in Umlazi, Durban

Summary: The study discovered that despite HIV being characterised as an immune suppressive disease, the initial immune response to HIV infection was much larger than previously appreciated. It also found that the strength of the initial response mediated by killer white cells called “killer lymphocytes” - also called CD8 T lymphocytes - play a crucial role in controlling HIV replication during the early phase of the disease. More importantly the research team discovered that the reason the initial immune response fails to completely eliminate the virus is because HIV induced killer lymphocyte die before completely eliminating HIV infected cells allowing the disease to progress.

 

Researcher: Ms Yashodani Pillay

Designation: PhD study

Study: Patulin triggers NRF2-mediated survival mechanisms in kidney cells

Summary: Patulin is produced by moulds that contaminate apples and apple products. Literature shows these foods are most popular among children, who are susceptible to toxic outcomes as their defense systems are still developing. The study findings revealed that PAT depleted glutathione – an agent pivotal to the cellular AO defense system. This action increased levels of damaging pro-oxidants (ROS) and triggered the up-regulation of Nuclear erythroid 2-related factor (NRF2) mediated AO mechanisms. This suggested that innate cell survival mechanisms involved with NRF2 signalling were activated in response to acute Patulin exposure. A recent study in animals showed Patulin is a potential initiator in tumorigenicity though its mechanistic role remains unclear. The study conducted may assist in understanding the part Patulin may play, though further work is needed to fully elucidate this mechanism.


Researcher: Ms Lavania Joseph

Designation: Masters Study

Study: Mutation frequencies in drug-susceptible clinical isolates of Mycobacterium tuberculosis under aerobic and anaerobic conditions

Summary: Drug resistance is one of the major obstacles threatening the success of tuberculosis (TB) control programs, particularly in KwaZulu-Natal.  Little was known about the ability of M. tuberculosis (the causative agent of TB) to acquire mutations leading to drug resistance.   The study aimed to provide much-needed information on the mutational capacity of M. tuberculosis, with potential implications for anti-tuberculosis therapy.

 

Researcher: Ms Camie Vallen

Designation: Honours Research

Study: Immunolocalization of HIV viral antigens and its receptors at the Maternal Fetal Interface in Normotensive and Pre-eclamptic Pregnancies

Summary: Mother to child transmission of HIV remains high despite the introduction of ARVs during pregnancy. The mechanism of HIV transmission across the placenta needs to be evaluated. This study aimed to evaluate expression of key receptors and co-receptors implicated in HIV transmission within the placental exchange villi.


Researcher: Professor Koleka Mlisana

Designation: PhD study

Study: The Impact of Sexually Transmitted Infections (STI) and Genital Tract Inflammation on HIV-1 Acquisition and Rate of Disease Progression in subtype C Infected women

Summary: The study assessed the adequacy of syndromic diagnosis of STIs, compared with laboratory diagnosis of STIs, and evaluated the association between STI diagnosis and the risk of HIV acquisition in a cohort of high-risk women. Genital cytokine profiles and the degree of inflammation associated with common STIs and bacterial vaginosis were assessed. The most common signs and symptoms of acute HIV infection (AHI) were described and a clinical algorithm to identify acute HIV cases was developed. The study also investigated rates of HIV disease progression of subtype C–infected South African women.

 

Researcher: Dr Saiyur Ramsugit

Designation: PhD study

Study: The role of Mycobacterium tuberculosis on pili adhesin

Summary: The study describes the identification of a novel adherence factor (adhesin) of the tuberculosis-causing bacterium. According to Ramsugit, more than a third of the world’s population is infected with TB, a disease that was responsible for 1.5 million deaths in 2013. He believes that reducing the global burden of TB requires the development of more effective treatment, diagnostic, and preventative strategies. This in-turn is dependent on a greater understanding of the mechanisms by which the pathogen is able to cause disease. Pili are hair-like structures present on the surface of several bacterial species. In this study, the gene that is responsible for pili formation was knocked out to create a mutant TB strain that lacked pili. The mutation was complemented, thereby creating a TB strain that produced excessive amounts of pili. The phenotype of the pili-proficient and pili-deficient strains was then compared. The results showed that the strains that expressed pili were better able to form a biofilm (ie a community of bacteria). Living as a community allows bacteria to become recalcitrant to antibiotics and, therefore, influence the way we treat these infections. The study also found that the strains expressing pili were better able to infect human cells than the strain lacking pili, without eliciting the host cytokine response. ‘Pili, therefore, function in these important aspects of TB pathogenesis. These results lead us to believe that developing drugs and vaccines targeting M. tuberculosis pili may hinder the ability of this organism to infect and persist in humans.

 

Researcher: Dr Mopo Radebe

Designation: PhD study

Study: Patterns and features of HIV-1-specific CD8+ T- cell responses during acute HIV-1 infection and their association with viral control

Summary: Evidence suggests that CD8+ T-cells play a major role in the control of HIV-1 viremia and apply significant immune pressure on HIV-1 replication. However, the presence of virus-specific CD8+ T-cells in individuals with varying levels of viral control suggests that CD8+ T-cells may differ in their antiviral function or efficacy.  The mechanisms underlying differences in the control of viremia, particularly the reasons why particular individuals experience more effective acute viremia resolution, which is a good correlate of the subsequent rate of disease progression, are still not well understood. In order to uncover some of the features of CD8+ T-cell subsets responsible for the control of HIV replication, particularly during the critical early infection phase, we investigated the patterns and features of HIV-1-specific CD8+ T-cell responses during acute and primary HIV-1 infection and their association with viral control.  The study also sought to determine the impact of acute phase immune activation on the acute HIV-1-specific CD8+ T-cell response and on disease progression. It found that responses directed at the HIV Gag protein are associated with viral control but show delayed appearance kinetics and do not always persist.  Furthermore, most immune responses generated during acute HIV infection did not cause harmful mutations in HIV.   This study provided a rational basis for the design of HIV vaccines.

 

Researcher: Dr Sarita Naidoo

Designation: PhD candidate

Study: Antimicrobial susceptibility testing of Trichomonas vaginalis susceptibility testing of Trichomonas vaginalis

Summary: Trichomonas vaginalis is the most common sexually transmitted infection caused by a single known organism worldwide; and has been associated with an increased risk of HIV acquisition and transmission.  Despite its high prevalence in South Africa, limited information is available on the extent of T. vaginalis metronidazole resistance and genotypic variation in this setting.  The study tested the susceptibility of local T. vaginalis isolates against metronidazole and drugs prescribed in combination in the context of syndromic management of vaginal discharge syndrome.  Susceptibility testing of 40 isolates demonstrated that metronidazole as well as some of the other drugs tested showed inhibiting effect on T. vaginalis.  We recommend that these drugs be tested for synergistic effect with metronidazole. In a different set of 160 isolates the minimum inhibitory concentrations (MIC) of metronidazole ranged from 1.1 µg/ml to > 34.2 µg/ml (6.25 µM to > 200 µM) in the aerobic assay.  Interpretation of these MICs differed based on the different resistance breakpoints applied.  There was no correlation between MIC and treatment outcome in the subset of 56 patients that returned for follow-up.  The expected association between MIC and clinical outcome was only observed in one of eight patients with unsatisfactory treatment outcome.  This patient‘s isolate had the highest MIC.  In the remaining seven patients with unsatisfactory treatment outcome, no relation with the susceptibility test result was found. A possible reason for the poor correlation may be inadequate concentration of metronidazole at the site of infection.  In view of this, the study assessed a self-administered and collected vaginal tampon specimen for the investigation of metronidazole concentration in the vagina of five healthy volunteers, using high performance liquid chromatography (HPLC). Maximum values of metronidazole concentrations detected in both serum and vaginal fluid were obtained at two hours following oral administration of 2 g of the drug. This method can be applied in future clinical studies to correlate treatment outcome and MICs with metronidazole concentration at the site of infection.  This may lead to the development of susceptibility assays and interpretation criteria that are better able to predict treatment outcome than the current methods.  Another reason for the poor correlation between treatment outcome and in vitro resistance may be early reinfection.  We used PCR-RFLP, targeting a 650-bp repeat region in the T. vaginalis genome, to genotype T. vaginalis isolates.  Four genotypes were found in 100 T. vaginalis isolates using this method. Both the vaginal secretion of metronidazole and the strain typing methodology needs to be further investigated before a comprehensive study as outlined above can be executed.


Researcher:  M. S. Passerotti, A. H. Andrews, J. K. Carlson, S. P. Wintner, K. J. Goldman and L. J. Natanson

Designation: Honorary Research Fellow

Study: Maximum age and missing time in the vertebrae of sand tiger shark (Carcharias taurus): validated lifespan from bomb radiocarbon dating in the western North Atlantic and southwestern Indian Oceans

Summary: Visual counts of vertebral growth bands were used to assign age and estimate year of formation (YOF) for sampled growth bands in eight sharks from the WNA and two sharks from the SIO. Carbon-14 results were plotted relative to YOF for comparison with regional Δ14C reference chronologies to assess the accuracy of age estimates. Results from the WNA validated vertebral age estimates up to 12 years, but indicated that ages of large adult sharks were underestimated by 11–12 years. Age was also underestimated for adult sharks from the SIO by 14–18 years. Validated lifespan for C. taurus individuals in the present study reached at least 40 years for females and 34 years for males. Findings indicated that the current age-reading methodology is not suitable for estimating the age of C. taurus beyond, 12 years. Future work should investigate whether vertebrae of C. taurus record age throughout ontogeny, or cease to be a reliable indicator at some point in time.

 

Researcher: Ms Arishka Kalicharan

Designation: Masters student

Study: The Morphology and Morphometry of the Femur in a KwaZulu-Natal population

Summary: The femur is the longest and strongest skeletal bone responsible for the gait and movement of the lower limbs. In the last fifteen years, there has been no study done in KwaZulu-Natal using dry bone femora hence this study aimed to investigate the morphometric and morphological parameters of the dry femora which can be useful in the field of anthropology and during bone grafting.

A total of 100 dry adult femora were obtained from the osteological bank at the Clinical Anatomy discipline, University of KwaZulu-Natal, Westville campus. Methodology was performed in accordance with Bokaryia et al. (2009). All nine measurements were done using a digital calliper. The statistical analysis was performed using SPSS version 22.0. A statistically significant value of < 0.05 was adopted.

The number of nutrient foramina found: (a) Single (left: 33.33%; right: 55.10%); (b) Double (left: 58.97%; right: 38.80%); (c) Triple (left: 7.70%; right: 6.10%). The mean length of the right femur was 44.45±2.88mm and 45.46±4.18mm for the left. The mean antero-posterior diameter of the shaft at upper segment was 28.02±2.46mm, middle segment was 29.09±2.13mm, and lower segment was 31.60±2.34mm. These measurement values were derived from a Black African and White population in KwaZulu-Natal. Statistically significant (p<0.001) differences were found in all parameters.

The results of this study compares favourably with previous studies. The left femora showed higher values for all parameters measured. The parameters measured can be useful to surgeons in bone grafting procedures as landmarks to avoid injury to such regions and prolong recovery.

Researcher: Dr Teke Apalata

Designation: PhD candidate

Study: Immunopathogenesis of Vulvo-vaginal Candidiasis in HIV-infected Women

Summary: In HIV infected women, vulvo-vaginal candidiasis (VVC) is recurrent and less responsive to conventional anti-fungal therapy. The quality of life is greatly diminished for women who experience recurrent episodes of VVC. The pathogenesis of recurrent VVC is not well understood.

Using a multifactorial design, the present study sought to further understand the pathogenesis of VVC and the associated host defense mechanisms in HIV infected women.

Findings of this study have showed that more than one pathogenic mechanism can explain the occurrence of VVC in HIV infected women. Of particular importance, Th17 and regulatory T cells (decrease of Th17/Treg ratio) rather than Th1/Th2 paradigm are key players in the defense and development of effector responses in the vagina of VVC patients co-infected with HIV. In addition, it was established that HIV induces lymphoid activation despite CD4+ T cell depletion in women with severe immunosuppression (CD4 < 200), reflected by increased production of MIP-1β and other markers of T cell activation such as CD38 and HLA-DR. This chronic immune activation was associated with HIV viral persistence and increased cases of VVC. The study has further shown a decrease in Toll-Like Receptors (TLR)-2 mediated responses by Candida in HIV infected women. The hypothesis that VVC in HIV infected women can be a result of either Candida-specific IgE production or histamine-induced prostaglandin E2 was shown to be relevant to only a group of women with specific underline conditions.

In conclusion, the interplay between infection and the immune system is intricate and relationships between factors not always explainable. It may be argued that this is a case of “cause and effect”. However, the occurrence of VVC with increasing immunosuppression in our population is of concern and different angles have to be explored in an effort to address this major public health problem.

 

Researcher: Dr Silindile Hadebe

Designation: PhD candidate

Study: Transdermal Delivery of Insulin by Amidated Pectin Hydrogel Matrix Patch in Streptozotocin Induced Diabetic Rats: Effects on Some Selected Metabolic Parameters

Summary: Studies in the Physiology laboratory are concerned with developing optional insulin delivery routes based on amidated pectin hydrogel matrix gel. The study investigated whether the application of pectin insulin (PI)-containing dermal patches of different insulin concentrations sustain controlled release of insulin into the bloodstream of streptozotocin (STZ)-induced diabetic rats with concomitant alleviation of diabetic symptoms in target tissues, most importantly, muscle and liver. The data suggest that the PI hydrogel matrix patch can deliver physiologically relevant amounts of pharmacologically active insulin. A new method to administer insulin into the bloodstream via a skin patch which could have potential future applications in diabetes management is reported.

Researcher: Dr Silindile Hadebe

Designation: PhD candidate

Study: The Effects of Transdermal Insulin Treatment of Streptozotocin-Induced Diabetic Rats on Kidney Function and Renal Expression of Glucose Transporters

Summary: The tight glycemic control required to attenuate chronic complications in type 1 diabetes mellitus requires multiple daily injections of bolus insulin which cause hyperinsulinemic edema and hypertension due to Na(+) retention. Reports indicate that pectin insulin (PI)-containing dermal patches sustain controlled insulin release into the bloodstream of streptozotocin (STZ)-induced diabetic rats. This study investigated whether PI dermal patches can improve the impaired renal function in diabetes. PI patches were prepared by dissolving pectin/insulin in deionized water and solidified with CaCl(2). Short-term (five weeks) effects of thrice daily treatments with PI patches on renal function and urinary glucose outputs were assessed in diabetic animals. Blood and kidney samples were collected after five weeks for measurements of selected biochemical parameters. Blood was also collected for insulin measurement 6 h following treatments. The low plasma insulin concentrations exhibited by STZ-induced diabetic rats were elevated by the application of insulin-containing dermal patches to levels comparable with control non-diabetic rats. Untreated STZ-induced diabetic rats exhibited elevated urinary glucose, K(+) outputs and depressed urinary Na(+) outputs throughout the 5-week period. Treatment with PI dermal patches increased urinary Na(+) output and reduced urine flow, urinary glucose and K(+) excretion rates in weeks 4 and 5. PI dermal patches increased GFR of diabetic rats with concomitant reduction of plasma creatinine concentrations. Transdermal insulin treatment also decreased the renal expressions of GLUT1 and SGLT1 of STZ-induced diabetic rats. We conclude that PI dermal patches deliver physiologically relevant amounts of insulin that can improve kidney function in diabetes.

 

Researcher: Dr Andile Khathi

Designation: PhD student

Study: Syzygium aromaticum-derived triterpenes modulate intestinal glucose handling in streptozotocin-induced diabetic

Summary: Polyphagia in diabetes mellitus ascribed to elevated plasma ghrelin concentrations is associated with prolonged postprandial hyperglycaemia due to increased activities of intestinal carbohydrate hydrolyzing enzymes and glucose transporters. Postprandial hyperglycaemia is a major risk factor in the development of diabetic complications and as such, should be managed to prevent chronic vascular complications. Previous studies in our laboratory have shown that Syzygium aromaticum-derived oleanolic acid (OA) and maslinic acid (MA) use various mechanisms to lower blood glucose concentrations in experimental diabetes. The effects of these triterpenes, however, on intestinal glucose handling remain unknown. Accordingly, this study was designed to investigate the effects of these triterpenes on intestinal glucose handling in STZ-induced diabetic rats.

 

Researcher: Dr Hlengiwe Madlala

Designation: PhD student

Study: Mechanisms of cardiovascular effects of oleanolic acid and related synthetic oleanane derivatives: an experimental study

Summary: This novel study investigated the potential of alternative medicine which would be accessible to communities from poor socio-economic backgrounds, introduced the first evidence that oleanolic acid and its oleanane derivatives induced similar effects exerting multiple blood pressure lowering mechanisms while increasing the force of cardiac contraction ‘hence balancing the fluid volume in the circulatory system so as to avoid a state of hypotension

 

Researcher: Dr Blessing Mkhwanazi

Designation: PhD student

Study: Effects of maslinic acid and related triterpene derivatives on kidney function of streptozotocin (STZ) induced diabetic rats

Summary: Reports indicate that hyperglycaemia leads to development of kidney complications which result in sodium retention, decrease in glomerular filtration rate (GFR) and high blood pressure. Various biochemical processes such as polyol pathway, AGEs formation are thought to gives rise to a development and progression of these complications. Clinical trials show that there is currently no commercially available compound that lowers blood glucose concentration while alleviating diabetic nephropathy (DN). Current methods involve the use of ACE blockers which are associated with side effects. Previous reports in our laboratories indicate that triterpene constituents of Syzygium spp. such as oleanolic acid (OA) possess hypoglycaemic and renoprotetive effects in STZ-induced diabetic rats. The important question is whether MA, a related triterpene also possesses the same properties. MA is a hydrophobic triterpene and we therefore synthesised derivatives to improve solubility, bioavailability and efficacy. Accordingly this study was designed to investigate the effects of MA and related triterpene derivatives on renal function of STZ-induced diabetic rats.

 

Researcher: Dr Phikelelani Ngubane

Designation: PhD student

Study: The effects of insulin and Syzygium cordatum-derived Oleanolic acid on kidney function and renal glucose transporters in diabetes

Summary: The tight glycaemic control required to attenuate chronic complications in type 1 diabetes mellitus requires multiple daily injections of bolus insulin which have been reported to be associated with Na+ retention resulting in hyperinsulinaemic oedema and hypertension. Current research on insulin delivery methods include buccal, oral, nasal, and transdermal delivery systems. Transdermal delivery system is of great interest as this offers sustained controlled release of insulin into the systemic circulation. We have previously reported that transdermal application of pectin hydrogel insulin (PI) matrix patches sustain controlled insulin delivery into the bloodstream of STZ-induced diabetic rats to perhaps ameliorate diabetic complications. Since the research group had reported that STZ-induced diabetic rats retain Na+ following hypotonic saline challenge, this study investigated whether insulin-containing dermal patches can avert and improve the impaired renal fluid and electrolyte handling of STZ-induced diabetic rats. The study also showed that oral administration of OA in addition to possessing hypoglycaemic effects, improves kidney function STZ-induced diabetic rats. The study therefore also investigated whether OA-containing dermal patches can improve kidney function STZ-induced diabetic rats.


Researcher: Ms Refilwe Molatlhegi

Designation: Masters candidate

Study: Antiproliferative Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line

Summary: The results of this study demonstrated that the cytotoxic properties of this novel synthesized compound could possibly be associated with its ability to down regulate the expression of antioxidant defense proteins (Nrf2 and SOD) and Hsp70 thus activating ROS overproduction. This ROS overproduction induced DNA damage (evidenced during Comet assay), which up-regulated the expression of tumor suppressor proteins such as p53. p53 activation down-regulated the expression of Bcl-2 thus activating the expression of Bax. Bax activation therefore resulted in mitochondrial polymerization and the release of cytochrome c as evidenced by a decrease in cellular ATP levels. The released cytochrome c then activated caspase-9, which subsequently resulted in activation of caspae-3/7 thus inducing a mitochondrial-mediated apoptosis of A549 lung cancer cells. However this was an in vitro work, therefore more work still need to be done in order for us to authenticate the cytotoxic pathway of this novel carbazole compound on A549 lung cancer cells before it can be tested in the animal models of lung cancer and then clinical trials.


Researcher: Ms Anushka Ajith

Designation: Lecturer

Study: The role of peripheral natural killer cells in immunocompromised pre-eclamptic and normotensive pregnant South African women

Summary: The aim of her study was to correlate the phenotypic properties of peripheral natural killer cells, CD3, CD16 and CD56 in normotensive pregnant women and pre-eclamptic counterparts in South Africa.  The study confirmed that an increased accumulation of NK cells were observed in pre-eclamptic compared to the normative pregnancies. It also demonstrated that a significant decrease in peripheral NK cells took place in the pre-eclamptic women and is continuing to look at the effect of HIV in pre-eclampsia.

 

Researcher: Dr Kaminee Maduray

Designation: Postdoctoral research

Study: A comparative morphometric evaluation of normotensive and pre-eclamptic placenta from South African pregnant women

Summary: In sub-Saharan Africa, pre-eclampsia is one of the major direct causes of maternal mortality. The pathology of pre-eclampsia is not fully understood. However, delivery of the placenta resolves all clinical symptoms and signs.  The placenta is therefore a vital organ in understanding the pathogenesis of pre-eclampsia. Objective: The aim of this study was to compare placentae morphometrics between normotensive and pre-eclamptic pregnancies. Methods: Placentae were collected from normotensive (n=30) and pre-eclamptic (n=30) pregnancies. At delivery, each placenta was photographed and analysed for variations in gross appearance, abnormalities, point of insertion of umbilical cord as well as thickness. The placental images were further analysed for placental volume and diameter with the Zeiss Axiovision Rel. 4.8 software. Results: Placentae of pre-eclamptic pregnancies showed more abnormalities with regards to shape and the presence of oedema compared to the normotensive group. Eccentric insertion of the umbilical cord was predominate in the normotensive (60%) compared to the pre-eclamptic (45%) group. Marginal insertion of the umbilical cord was found in 27% and 28% of the normotensive and pre-eclamptic group respectively; whilst central insertion was noted in 13% of the normotensive and 10% in the pre-eclamptic group. Velamentous insertion occurred in the pre-eclamptic (17%) but was absent in the normotensive pregnancies. The mean placental weight, thickness, diameter and volume in the normotensive group were 675 g, 1.6 cm, 27 cm and 1024 cm3 respectively; and those in the pre-eclamptic group were 577 g, 1.5 cm, 25 cm and 743 cm3 the respectively. Conclusion: This study concludes that the mean placental weight, thickness, diameter and volume were significantly lower in pre-eclampsia compared to normotensive pregnancies. 

Researcher: Dr Myint Aung

Designation: PhD research

Study: Gene polymorphisms of the Renin-Angiotensin system, AT1, AT2 and AT4 gene expressions in placenta  and circulating Angiotensin II antibodies in pre-eclamptic African Women

Summary: The study aims to determine whether genetic variants of the components of the RAS (Angiotensinogen, Renin, ACE and AT1 and AT2 receptors) occur in pre-eclamptic women. 

Researcher: Ms Savania Nagiah

Designation: PhD candidate

Study: The effect of nuclease reverse transcriptase inhibitor (NRTIs) on mitochondrial integrity and the Nrf2-mediated oxidative stress response in HepG2 liver cells

Summary: NRTIs for the backbone of modern highly active antiretroviral therapy (HAART). As HAART has significantly prolonged the life span of HIV infected individuals, long term side effects of the drugs are beginning to emerge. The most concerning among these is changes to metabolic parameters, favouring insulin resistance, lipodystrophy and sometimes leading to heart disease. A common underlying molecular mechanism to these adverse health outcomes is the over-production of free radicals. The condition under which antioxidant defence against free radical damage is exhausted is known as oxidative stress. This study investigated stress responses that overlap in both oxidative stress and mitochondrial stress response, linking to pathological mechanisms in NRTI use. Gaining insight to these molecular mechanisms will aid in uncovering preventative measures or possible therapeutic interventions. 

Researcher: Ms Zinhle Mvelase

Designation: PhD candidate

Study: The effects of vanadium complexes combined with hypoglycaemic agents on glucose utilization in the liver and muscle cell lines

Summary: The study aimed to investigate the effects of vanadium complexes in combination with anti-hyperglycaemic agents in glucose metabolism of liver and muscle cell lines in vitro and the results suggested that a combination administration of hpybz (VO) 2 with insulin was effective in glucose utilisation compared to a single drug administration in liver and muscle cell lines, in vitro. It concluded that the administration of hpybz (VO) 2 in combination with insulin may be beneficiary in the management of diabetes mellitus.


Researcher: Mr Ugochukwu Offor

Designation: Masters candidate

Study: Renal histomorphological changes following highly active antiretroviral therapy: Possible role of Hypoxis hemerocallidea in an experimental animal model

Summary: Nephrotoxicity has become an important public health problem following highly active antiretroviral therapy (HAART), and there is paucity of literature reporting the attenuating influence of plant based adjuvant that can mitigate the effects. The study investigates the role Hypoxis hemerocallidea (AP) extract following HAART in an experimental animal model.

Sixty three adult male Sprague-Dawley rats were used for the study and were divided into 9 groups (A-I), where group A-H served as the experimental groups while group I served as the control. The experiment lasted for 56 days after which, the animals were sacrificed, the kidneys were harvested and prepared for H&E histological examination and blood samples were collected through cardiac puncture and centrifuge to get the serum for blood urea nitrogen and Serum creatinine analysis.

Organ-body weight ratios were significantly higher in group A and group F (p<0.05).

Serum Creatinine (SCR) and blood urea nitrogen (BUN) levels were statistically elevated in HAART-treated animals (p<0.05, 0.001). SCR levels in group D was significantly reduced (p<0.05) but however, significantly elevated in groups B, C, G and H (p<0.001). Groups B and C, as well as groups F and H resulted in higher BUN values (p<0.05). The histological appearance of group A was highly compromised. When treated concomitantly with AP (at both dosages), no attenuating influence was seen. However, low dose of AP showed improved histological layout as compared to the high dose. Co-administration of HAART and combined dose of vitamin C and E did not improve the histoarchitecture.

Adjuvant treatment with HH extract did not attenuate the nephrotoxicity of HAART in this model.



Researcher: Mr Ugochukwu Offor

Designation: Honours

Study: Kolaviron Ameliorates Nevirapine-Induced Renal Histoarchitectural Damage

Summary: Results shows that oral administration of Nevirapine at 1.54mg/kgbw is nephrotoxic as seen in the histological slides in the Nevirapine group. Also kolaviron and nevirapine was toxic when administered concomitantly for 28days. Cross sections of kidney shows gross erosion of the architecture of the glomerular apparatus in Nvp only group. The concomitant administration of kolaviron and nevirapine once (200mg/kgbw/1.54mg/kgbw) was seen to attenuate this nephrotoxic effect as evidence in the improvement seen in the histology of the group given kolaviron and nevirapine. The group that was administered with vit c (250mg/kgbw) also show an improved histoarchitecture when compared with nevirapine administered group. The study found that adjuvant treatment with kolaviron (an antioxidant) did not attenuate the nephrotoxicity of Nvp in this model.


Researcher: Mr Ernest Dalle

Designation: PhD candidate

Study: The identification of a possible biomarker for cognitive impairment

Summary: Alzheimer’s disease is a non-curable neurodegenerative disease, hence there is a constant search for novel therapies. However, the lack of reliable biomarkers has made the evaluation of new treatments difficult. The aim of our study was to use an animal model to search for a novel biomarker that reflected the cognitive impairment of Alzheimer’s disease. The Ethics Clearance number was 011/13/Animal. Sprague-Dawley rats, received 10µl of β-amyloid (88.63mg/ml) directly into the dorsal hippocampus to induce cognitive impairment. Spatial learning and memory tests were conducted with the Morris Water Maze (MWM) before and after the bilateral intra-hippocampal injections. Control animals received 10µl of saline. Animals were sacrificed on day 3, 7, 10 and 14 following the intracerebral injection. Blood was collected via cardiac puncture of the left ventricle. Microwave technology was used to detect the conductivity and dielectric constant of plasma samples collected. Prior to the intra-hippocampal injections, all the animals displayed excellent learning ability in the MWM. On all 4 days tested, all animals exhibited excellent recall of their memory. The average conductivity and dielectric constants of the plasma of β-amyloid treated animals were also similar to controls on all 4 days investigated. Although our study was unable to statistically show that intracerebral injection of β-amyloid into the dorsal hippocampus lead to cognitive impairment, experimental rats have shown a tendency to increase their time to find the platform compared to normal rats. Interestingly, plasma of experimental animals compared to normal plasma has exhibited distinct variation of dielectric constant and conductivity.


Researcher:  Ms Nerissa Naidoo

Designation: PhD candidate

Study: An Anatomical Investigation of the Subacromial Complex: Intrinsic and Extrinsic Parameters of the South African and Belgian Populations

Summary: The study pertained to the field of Clinical Human Anatomy, specifically the intrinsic and extrinsic factors regarding the subacromial anatomical complex of the shoulder, with the aim of providing the clinician with reliable reference parameters indicative of underlying pathology which cannot be identified from a mere morphological observation. 


Researcher: Ms Lynne de Welzen

Designation: SLMMS K-Rith Researcher

Study: Whole Transcriptome Analysis of Drug Susceptible and Drug Resistant Isolates of Mycobacterium Tuberculosis using RNA-Seq

Summary: The study aimed to identify novel transcriptional changes in Mycobacterium Tuberculosis that could lead to drug resistance or compensate for loss of fitness or function due to a drug resistance conferring mutation. It  examined whether there were additional methods of drug resistance in M. tuberculosis by looking at the genetic level, ie the level of RNA.


Researcher: Mr Saiyur Ramsugit.

Designation: Post Doc student in the Medical Microbiology and Infection Control Academic Unit in the School of Laboratory Medicine and Medical Sciences

Study: Mycobacterium Tuberculosis pili (MTP) Promote Adhesion to and Invasion of THP-1 Macrophages

Summary: Central to the paradigm of the pathogenesis of Mycobacterium tuberculosis is its ability to attach to, enter, and subsequently survive in host macrophages. However, little is known regarding the bacterial adhesins and invasins involved in this interaction with host macrophages. Pili are cell-surface structures produced by certain bacteria and have been implicated in adhesion to and invasion of phagocytes in several species. M. tuberculosis pili (MTP) are encoded by the Rv3312A (mtp) gene. In the present study, we assessed the ability of a Δmtp mutant and an mtp-complemented clinical strain to adhere to and invade THP-1 macrophages in comparison with the parental strain by determining colony-forming units. Both adhesion to and invasion of macrophages, although not reaching significance, were markedly reduced by 42.16% (P = 0.107) and 69.02% (P = 0.052), respectively, in the pili-deficient Δmtp mutant as compared with the wild-type. The pili-overexpressing complemented strain showed significantly higher levels of THP-1 macrophage adhesion (P = 0.000) and invasion (P = 0.040) than the mutant. We, thus, identified a novel adhesin and invasin of M. tuberculosis involved in adhesion to and invasion of macrophages.

Study: Mycobacterium tuberculosis adhesins: Potential biomarkers as anti-tuberculosis therapeutic and diagnostic targets

Summary: Adhesion to host cells is a precursor to host colonization and evasion of the host immune response. Conversely, it triggers the induction of the immune response, a process vital to the host's defence against infection. Adhesins are microbial cell surface molecules or structures that mediate the attachment of the microbe to host cells and thus the host-pathogen interaction. They also play a crucial role in bacterial aggregation and biofilm formation. In this review, we discuss the role of adhesins in the pathogenesis of the aetiological agent of tuberculosis, Mycobacterium tuberculosis. We also provide insight into the structure and characteristics of some of the characterized and putative M. tuberculosis adhesins. Finally, we examine the potential of adhesins as targets for the development of tuberculosis control strategies.

Study: Pili of Mycobacterium tuberculosis: current knowledge and future prospects

Summary: Many pathogenic bacteria express filamentous appendages, termed pili, on their surface. These organelles function in several important bacterial processes, including mediating bacterial interaction with, and colonization of the host, signalling events, locomotion, DNA uptake, electric conductance, and biofilm formation. In the last decade, it has been established that the tuberculosis-causing bacterium, Mycobacterium tuberculosis, produces two pili types: curli and type IV pili. In this paper, we review studies on M. tuberculosis pili, highlighting their structure and biological significance to M. tuberculosis pathogenesis, and discuss their potential as targets for therapeutic intervention and diagnostic test development.


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