Browsing by Author "Marais, A David"

Now showing 1 - 10 of 10
  • Thumbnail Image
    Item
    Open Access
    Coastal resources and nutrition among Middle Stone Age hunter-gatherers in the Southwestern Cape
    (2014) Kyriacou, Katharine; Parkington, John; Marais, A David
    This thesis presents new information on the macronutrient, micronutrient and fatty acid content of marine and terrestrial resources available to Middle Stone Age hunter-gatherers in the southwestern Cape, and examines the role of coastal and terrestrial foods in the diets of early modern humans in the region. The collection, consumption and systematic discard of intertidal molluscs by prehistoric people is firmly attested by the presence of shellfish residues at archaeological sites dating to the Last Interglacial (120 000 years ago) at Klasies River Mouth, Blombos Cave, Hoedjiespunt and Sea Harvest, or earlier (164 000 years ago) at Pinnacle Point. The incorporation of marine foods into the diet is one of several forms of innovative behaviour characteristic of the Middle Stone Age. Classification of fossil hominin remains from key sites in southern Africa as anatomically modern further marks the Middle Stone Age as a crucial stage in the evolution of our species. The apparent link between coastal resources, innovative behaviour and anatomical modernity is tantalising, and in need of further exploration. The nutrient content of one hundred and twenty three samples from a range of marine and terrestrial animals and plants known or presumed to have been eaten by Middle Stone Age hunter-gatherers in the southwestern Cape was measured using spectrophotometry and gas chromatography. When interpreted against existing knowledge on prehistoric subsistence strategies and ecology, these results provide a quantitative framework within which the relative utility of marine and terrestrial resources as a nutritional substrate for encephalising humans is evaluated. While terrestrial foods would have provided prehistoric people with sufficient energy and trace elements, sources of long-chain polyunsaturated fatty acids would have been limited. Marine foods, including intertidal mussels and limpets, are rich in the two most important omega-3 fatty acids found in the human brain, namely eicosapentaenoic and docosahexaenoic acid. The inclusion of coastal resources, particularly sessile, abundant, predictable and easily collected marine molluscs, in the diet would have been highly advantageous for groups of early modern humans in the vicinity of the Atlantic west coast. Pregnant and lactating women and very young children, who have some of the highest requirements for brain-specific nutrients, are likely to have benefitted the most.
  • Thumbnail Image
    Item
    Open Access
    Dried spot cards to analyse biologic fluids for diagnostic investigation of patients
    (2018) Rapulana, Antony Morwamoche; Blackhurst, Dee M; Marais, A David
    Background: Collection of biologic fluid for laboratory analysis requires relatively large samples, often with additives, and transport in fragile tubes. The analytes or matrices may be unstable so testing needs to be carried out quickly. Collection of these biologic fluids and drying them on filter paper can lower the cost of transporting the sample to the laboratory, avoid instability of the matrix, and degradation of the analytes. Aim: The aim of this project was to develop an inexpensive, convenient, comprehensive and reproducible patient sample collection system which ensures integrity and ease of transport of small-scale samples at room temperature, as well as ensuring convenient long-term storage for subsequent analysis. Methods: Samples (blood, buffy coat, serum, plasma and urine) were collected into various tubes and spotted onto filter paper cards. Concentrations of total cholesterol, triglyceride, phospholipids, glucose, lactate, and protein were measured in the original sample and dried plasma spots (DPS) and the concentration of creatinine was measured in urine and dried urine spots (DUS). Determination of oxidation of lipids by measurement of conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS) on dried serum spots (DSS) was carried out. Determination of salicylate on serum and dried serum spots and cyanide on whole blood and dried blood spots was carried out. Values obtained from original samples and dried spots were compared. In addition, DNA extracted from a dried buffy coat spot (DBCS) from a familial hypercholesterolemia patient was analysed after spotting. Results: The total cholesterol, triglyceride, phospholipid, glucose, lactate and protein concentration values of 14 samples were compared in whole plasma and DPS stored at different temperatures. These were highly correlated after 1 week and 3 months of collection and storage. Plasma cholesterol, glucose and lactate concentration values for DPS as well as urinary creatinine for DUS at 1 week were not significantly different to that at both 3 and 7 months’ analyses (p>0.05). Plasma triglyceride and phospholipid concentrations were significantly different (p blood vs DBS respectively) for cyanide. Salicylate in DSS and cyanide in DBS were not significantly different to the original samples (paired t-test, p>0.05). Conclusion: Dried filter spots may be used to transport and store biologic fluid samples for analyses of a number of water-soluble and water-insoluble analytes. To protect lipids from being oxidised, the filter paper should be pre-treated with BHT.
  • Thumbnail Image
    Item
    Open Access
    Dysbetalipoproteinaemia : clinical and laboratory aspects, changes in lipoprotein composition and remnant metabolism associated with lipid lowering drugs
    (2007) Blom, Dirk Jacobus; Marais, A David
    This thesis examines and reviews multiple aspects of dysbetalipoproteinaemia. Dysbetalipoproteinaemia is a severe, highly atherogenic mixed hyperlipidaernia characterized by the accumulation of remnants of triglyceride-rich lipoproteins. Genetic susceptibility is conferred by mutations in apolipoproteinE, but manifest hyperlipidaemia often only occurs in the presence of metabolic abnormalities that influence lipoprotein production or clearance. Normal lipid metabolism is briefly reviewed to enable a better understanding of the pathophysiology of dysbetalipoproteinaernia. Hepatic remnant clearance is reviewed in detail with particular emphasis on the roles of all hepatic lipoprotein receptors. The importance of differential hepatic lipoprotein receptor binding affinities according to apoE mutation is emphasized.
  • Thumbnail Image
    Item
    Restricted
    Dyslipidaemia in South Africa
    (2004) Marais, A David
    Dyslipidaemia refers to the abnormal metabolism of lipids, as measured in the blood. Triglycerides (triacylglycerol) and total cholesterol (free and esterified cholesterol) are commonly implicated in hyperlipidaemias. These lipids are transported together with proteins as lipoproteins, which are named according to their ultracentrifugal properties: very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and chylomicrons. Dyslipoproteinaemia refers to abnormalities of the lipoproteins. Understanding metabolism at a molecular level has made it possible to better define dyslipidaemias, their prevalences and phenotypes as recently described in the South African context.
  • Thumbnail Image
    Item
    Open Access
    Familial Defective binding apolipoprotein B-100 the Cape Town Experience
    (2009) Mahala, Bonginkosi; Marais, A David
  • Thumbnail Image
    Item
    Open Access
    Familial hypercholesterolaemia: the Cape Town experience
    (Health and Medical Publishing Group, 2008) Firth, Jean C; Marais, A David
    Familial hypercholesterolaemia (FH), an autosomal dominantly inherited disorder characterised by elevated plasma low-density lipoprotein (LDL) cholesterol levels, tendon xanthomata and premature ischaemic heart disease, is amenable to treatment with modern medication. The clinical and biochemical details of 1 031 patients with FH were analysed. FH is the most common monogenic disorder of lipoprotein metabolism presenting to the Lipid Clinic at Groote Schuur Hospital, accounting for about 20% of consultations. The hospital classified 55% of the FH patients as white, 43% as coloured, 1.5% as Asian and 0.5% as black. In the FH cohort (whose mean age at presentation was 44 years), 80% had tendon xanthomata, 36% had arcus cornealis, and 14% had xanthelasma. Tendon xanthomata was present in almost 90% of patients by the age of 50 years. Arcus cornealis was present in about 45% by the age of 40 years, further increasing in frequency with age. Cardiovascular complications included ischaemic heart disease (43%), stroke (1.5%), transient ischaemic attacks (1.3%), and peripheral vascular disease (3.7%). The mean age of death was 55 (+13) years; 51 (+10) years in men and 61 (+12) years in women. In 46% of the cohort, a defective gene was identified by testing for locally prevalent mutations.
  • Thumbnail Image
    Item
    Open Access
    The molecular and cellular defect underlying autosomal recessive hypercholesterolemia (ARH) in the first kindred identified in South Africa
    (2005) Abera, Aron; Henderson, Howard; Marais, A David
    Monogenic defects in the low density lipoprotein (LDL) uptake pathway occur commonly in South Africans, particularly in the Afrikaner community where inheritance is typically autosomal dominant, arising predominantly from abnormal structure and thus function of the LDL receptor (LDLr). Defects in LDLr binding domain of apolipopreteinB-100 (apoB-100) are rarely encountered and are know as Familial defective apoB-100 (FDB). Several critical proteins are active in the LDL uptake pathway and their deficiencies are now being shown to underlie the rare autosomal recessive forms of hypercholesterolemia (ARH). One of these proteins is the LDLr adaptor protein know as ARH, which is presumed to facilitate interaction of the cytoplasmic tail of the LDLr with the internal protein matrix required for the receptor internalisation.
  • Thumbnail Image
    Item
    Open Access
    Potential cardioprotective effect of chronic, moderate consumption of reduced-alcohol wine in a rat model of pulmonary hypertension
    (2018) Diaba-Nuhoho, Patrick; Blackhurst, Dee; Sandrine, Lecour; Marais, A David
    Background: Pulmonary arterial hypertension (PAH) is a severe disease which leads to right ventricular (RV) dysfunction and possibly death. The pathophysiological process of PAH remains unclear but oxidative stress is thought to contribute to arterial and ventricular dysfunction. Red wine has powerful antioxidant properties and is cardioprotective. However, side effects of alcohol may limit the use of wine as a therapeutic agent. The aim of this study was to test whether reduced-alcohol red wine (RARW) or regular red wine (RW) consumption would limit monocrotaline (MCT)-induced PAH in rats. Methods: Long Evans male rats (150-175g) were randomly assigned into 6 groups: (1) Control: no subcutaneous injection of MCT; (2) MCT; (3) RARW; (4) MCT-Treated with RARW: 5.5% alcohol red wine (5) RW and (6) MCT-Treated with RW: 15% alcohol red wine. The wines were diluted with water (1:7), to supply an equivalent of 2-3 glasses daily consumed in humans ad libitum for 7 days before MCT treatment and for 28 days after MCT treatment with 80mg/kg. The stability of the wine was determined for 4 weeks by analysing ORAC values, total phenolic concentration, anthocyanin and catechin concentrations. Prior to randomisation, and at day 28, echocardiography (VEVO 2100, Visualsonics Inc.) was performed to evaluate pulmonary artery acceleration time (PAAT), an accurate estimate of pulmonary artery pressure, PAAT/Ejection fraction and RV thickness as a marker of RV hypertrophy. Oxidative stress was evaluated by measuring lipid peroxidation markers (conjugated dienes (CD), thiobarbituric acid reactive substances (TBARS)) and antioxidant measures of oxygen radical absorbance capacity (ORAC), superoxide dismutase (SOD) and catalase (CAT) activities in blood plasma were analysed. Results: Baseline echocardiography showed similar cardiac function amongst all groups. MCT injection induced right ventricular hypertrophy compared to controls (1.22 ± 0.01 mm and 0.52 ± 0.04 mm; p< 0.0001). A decrease in PAAT was observed in the MCT group compared to controls (13.95 ± 0.95 vs 23.43 ± 1.64 ms, p< 0.001). However, MCT treatment with RARW ameliorated the trend in the MCT group (18.93 ± 1.80 vs 13.95 ± 0.95 ms, p=0.02). Similarly, PAAT/Ejection fraction in the MCT group was reduced compared to the control group (0.18 ± 0.02 ms and 0.32 ± 0.18 ms; p< 0.001). Chronic moderate treatment with RARW in PAH animals improved hypertrophy and PAAT/Ejection fraction (0.85 ± 0.07 mm; P< 0.001and 0.25 ± 0.30 ms, respectively; p=0.02 versus the MCT group). Oxidative stress markers showed an increase in CD amongst animals with MCT compared to controls (671.60 ± 42.53 nmol/L and 453.10 ± 34.76 nmol/L; p=0.004). Chronic moderate treatment with RARW reduced lipid peroxidation (CD: 471.60 ± 27.45 nmol/L; p=0.004 versus the MCT group). Plasma TBARS, ORAC, SOD and CAT were not significantly affected by the condition or the treatment. The RARW had a consistently higher antioxidant status than the RW for the duration of the study. The mean concentration of RARW to the RW after 4 weeks in the total phenol was (291.90 ± 10.42 vs 235.80 ± 9.22 mg/L, p=0.006), that of the anthocyanins was (190.00 ± 3.53 vs 172.20 ± 5.13 mg/L M-3-G, p=0.0008), that of catechin was (12.06 ± 0.31 vs 10.26 ± 0.19 mg/L, p=0.157), and that of ORAC was (32.55 ± 2.75 vs 26.55 ± 2.37 nmol/L trolox equivalents, p=0.983). Conclusion: This study suggests that a moderate and chronic treatment with RARW but not RW attenuates MCT-induced PAH in rats, an effect which may be mediated, at least in part, by reduction of lipid peroxidation. The use of RARW could be tested in a randomised controlled trial and may be more beneficial than RW. This simple, inexpensive treatment might represent a new therapeutic option for PAH
  • Thumbnail Image
    Item
    Open Access
    Potential health benefits of antioxidant effects of wine on lipids
    (2005) Blackhurst, Diane Mary; Marais, A David
    The consumption of wine dates back to the Stone Age, but its potential health benefits only really began to make an impact after the French Paradox was postulated by Renaud and de Lorgeril in the 1990s. Their observations indicated that moderate consumption of red wine may have health benefits. Research since then has shown that wine, in particular red wine, is a source of a large number of different polyphenolic compounds that have antioxidant activity. The finding that the consumption of red wine might have a beneficial health effect was very appealing, resulting in a large number of epidemiological and experimental studies. To date, controversy still surrounds wine and its health effects. Several pertinent questions are still to be answered: What in vitro methods can be used to determine the antioxidant effects of wine? What are some of the in vivo effects of wine? Can wine be used directly as an antioxidant in cooking of the food that would ordinarily be exposed to conditions that may induce peroxidation of lipids? What effects does wine have at the cellular level?
  • Thumbnail Image
    Item
    Open Access
    Simvastatin enhances protection against Listeria monocytogenes infection in mice by counteracting Listeria-induced phagosomal escape
    (Public Library of Science, 2013) Parihar, Suraj P; Guler, Reto; Lang, Dirk M; Suzuki, Harukazu; Marais, A David; Brombacher, Frank
    Statins are well-known cholesterol lowering drugs targeting HMG-CoA-reductase, reducing the risk of coronary disorders and hypercholesterolemia. Statins are also involved in immunomodulation, which might influence the outcome of bacterial infection. Hence, a possible effect of statin treatment on Listeriosis was explored in mice. Statin treatment prior to subsequent L. monocytogenes infection strikingly reduced bacterial burden in liver and spleen (up to 100-fold) and reduced histopathological lesions. Statin-treatment in infected macrophages resulted in increased IL-12p40 and TNF-α and up to 4-fold reduced bacterial burden within 6 hours post infection, demonstrating a direct effect of statins on limiting bacterial growth in macrophages. Bacterial uptake was normal investigated in microbeads and GFP-expressing Listeria experiments by confocal microscopy. However, intracellular membrane-bound cholesterol level was decreased, as analyzed by cholesterol-dependent filipin staining and cellular lipid extraction. Mevalonate supplementation restored statin-inhibited cholesterol biosynthesis and reverted bacterial growth in Listeria monocytogenes but not in listeriolysin O (LLO)-deficient Listeria . Together, these results suggest that statin pretreatment increases protection against L. monocytogenes infection by reducing membrane cholesterol in macrophages and thereby preventing effectivity of the cholesterol-dependent LLO-mediated phagosomal escape of bacteria.