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Dawn Tladi,1 Lucky Mokgatlhe,2 Theo Nell,3 Sheila Shaibu,4 Ronel Mitchell,5 Comfort Mokgothu,1 Tebogo Gabonthone,1 Omphile Hubona1 1Department of Sport Science, University of Botswana, Gaborone, Botswana; 2Department of Statistics, University of Botswana, Gaborone, Botswana; 3Centre for Cardio-metabolic Research in Africa (CARMA), Integrated Metabolic Research Group, Department of Physiological Sciences, Faculty of Natural Sciences, University of Stellenbosch, Stellenbosch, 7600, South Africa; 4School of Nursing and Midwifery, The Aga Khan University, Nairobi, Kenya; 5Gaborone Biokinetics, Gaborone, BotswanaCorrespondence: Dawn TladiDepartment of Sport Science, Private Bag 00702, Gaborone, BotswanaTel +267 71896028Fax +267 3185096Email tladidm@ub.ac.bwPurpose: The metabolic syndrome (MetS) is on the rise in Sub-Saharan Africa, attributed to increased and uncontrollable urbanization accompanied by its lifestyle changes. Non-communicable diseases, such as hypertension, diabetes, and obesity, which are components of the (MetS) are also on the increase in Botswana. To date, no study has determined the prevalence of the MetS in the apparently healthy Batswana adults. The objective of the study was to determine the prevalence of the MetS among the 25– 65-year-old Batswana residing in urban and neighboring semi-urban areas of Gaborone.Participants and Methods: A cross-sectional study was used to collect data from N=794 participants, n=383 men and n=411 women, residing in Gaborone and two surrounding semi-urban areas. Data collected included demographic, anthropometric measurements, blood pressure (BP), blood glucose, triglycerides, high-density lipoprotein cholesterol (HDL-C) and total cholesterol.Results: A high prevalence of 26.8% was reported, with women mostly afflicted (35.0% vs 18.0%). The MetS risk factors found to be common in women were low HDL-C at (50% vs 48.7%) compared to men, while proportions with elevated BP (50.3% vs 39.4%) were prominent in men. The prevalence increased with age, with the oldest age group showing a higher prevalence in both women and men, respectively (55– 65 years; 38.5% vs 41.2%).Conclusion: An unprecedented high MetS prevalence was revealed among perceived to be healthy Batswana adults, with women at a higher risk. This public health concern creates an opportunity to establish evidence of risk factors, develop guidelines and strategies with appropriate public health measures to prevent and control the MetS.Keywords: abdominal obesity, HDL-C, blood pressure, age, public health

Although rollout of combined antiretroviral treatment (cART) has blunted human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) onset, there is increased development of cardiovascular diseases (CVDs) in HIV-infected individuals. While most HIV-infected individuals on cART achieve viral suppression, this may not necessarily result in complete immunological recovery. This study therefore evaluated T-cell-mediated changes and coagulation markers in HIV-positive individuals to ascertain their potential to increase CVD risk. Eighty participants were recruited (Worcester, South Africa), and fasted blood was collected to evaluate: 1) immune activation (CD38 expression on CD4+and CD8+T cells) and thrombus formation [tissue factor (CD142)] on CD4+and CD8+T cells; 2) monocyte subpopulations (nonclassical, intermediate, and classical); and 3) classical regulatory T (Treg) cells with activation markers [glycoprotein A repetitions predominant (GARP) and special AT-rich sequence-binding protein 1 (SATB-1)]. High- and low-density lipoprotein subclasses (Lipoprint) were also determined. This study revealed four key findings for HIV-positive patients: 1) coexpression of the CD142 coagulation marker together with immune activation on both CD4+and CD8+T cells during chronic infection stages; 2) Treg cell activation and upregulated GARP and SATB-1 contributing to Treg dysfunction in chronic HIV; 3) proatherogenic monocyte subset expansion with significant correlation between T-cell activation and macrophage activation (marker: CD163); and 4) significant correlation between immune activation and lipid subclasses, revealing crucial changes that can be missed by traditional lipid marker assessments (LDL and HDL). These data also implicate lipopolysaccharide-binding protein as a crucial link between immune activation, lipid alterations, and increased CVD risk.NEW & NOTEWORTHY With combined antiretroviral treatment rollout, HIV-AIDS patients are increasingly associated with cardiovascular diseases onset. This study demonstrated the significant interplay between adaptive immune cell activation and monocyte/macrophage markers in especially HIV-positive individuals with virological failure and on second line treatment. Our data also show a unique link between immune activation and lipid subclass alterations, revealing important changes that can be missed by traditional lipid marker assessments (e.g., LDL and HDL).

Adipocytes in the breast tumour microenvironment promotes acquired treatment resistance. We used an in vitro adipocyte-conditioned media approach to investigate the direct paracrine effects of adipocyte secretory factors on MDA-MB-231 breast cancer cells treated with doxorubicin to clarify the underlying treatment resistance mechanisms. Cell-viability assays, and Western blots were performed to determine alterations in apoptotic, proliferation and lipid metabolism protein markers. Free fatty acids (FFA) and inflammatory markers in the collected treatment-conditioned media were also quantified. Adipocyte secretory factors increased the cell-viability of doxorubicin-treated cells (p < 0.0001), which did not correspond to apoptosis or proliferation pathways. Adipocyte secretory factors increased the protein expression of hormone-sensitive lipase (p < 0.05) in doxorubicin-treated cells. Adipocyte secretory factors increased the utilization of leptin (p < 0.05) and MCP-1 (p < 0.01) proteins and possibly inhibited release of linoleic acid by doxorubicin-treated cells (treatment-conditioned media FFA profiles). Adipocyte secretory factors induced doxorubicin treatment resistance, by increasing the utilization of inflammatory mediators and inhibiting the release of FFA by doxorubicin-treated cells. This further promotes inflammation and lipid metabolic reprogramming (lipid storage) in the tumour microenvironment, which breast cancer cells use to evade the toxic effects induced by doxorubicin and confers to acquired treatment resistance.

Background A strong correlation exists between type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), with CVD and the presence of atherosclerosis being the prevailing cause of morbidity and mortality in diabetic populations. T2DM is accompanied by various coagulopathies, including anomalous clot formation or amyloid fibrin(ogen), the presence of dysregulated inflammatory molecules. Platelets are intimately involved in thrombus formation and particularly vulnerable to inflammatory cytokines. Methods The aim of this current study was therefore to assess whole blood (hyper)coagulability, platelet ultrastructure and receptor expression, as well as the levels of IL-1β, IL-6, IL-8 and sP-selectin in healthy and diabetic individuals. Platelet morphology was assessed through scanning electron microscopy (SEM), while assessment of GPIIb/IIIa receptor expression was performed with confocal microscopy and flow cytometry with the addition of FITC-PAC-1 and CD41-PE antibodies. IL-1β, IL-6 and IL-8 and sP-selectin levels were assessed using a multiplex assay. Results In T2DM there is significant upregulation of circulating inflammatory markers, hypercoagulation and platelet activation, with increased GPIIb/IIIa receptor expression, as seen with flow cytometry and confocal microscopy. Analyses showed that these receptors were additionally shed onto microparticles, which was confirmed with SEM. Conclusions Cumulatively, this provides mechanistic evidence that pathological states of platelets together with amyloid fibrin(ogen) in T2DM, might underpin an increased risk for cardiovascular events.

Background: Cardiovascular diseases (CVD) remains a primary cause of (central) obesity-associated mortality among African populations. Measures of adiposity are reported as prevalence’s in a South African (SA) female farm working population at risk for cardio-and metabolic disease related to body mass index, (BMI), waist-to-hip ratio (W:H), waist circumference (WC) and visceral adiposity index (VAI), biochemical and metabolic blood parameters.Methods: A cross-section of female farm workers (n=120) from the Boland region in SA between the ages 20-60 years were recruited and classified according to different anthropometric indices including BMI, W:H, WC and the VAI, and subsequently divided into normal- and at risk groups for each index. Blood samples were analysed for inflammatory markers, serum insulin, glucose and a full lipid profile.Results: Prevalence’s and significant differences for the different adiposity measures between normal and overweight groups were: (BMI: 25.8% - 74.2%; p

Background The global burden of type 2 diabetes mellitus (T2DM), together with the presence of cardiovascular risk in this population, is reaching pandemic levels. A prominent feature of T2DM is chronic and systemic inflammation, with the accompanying presence of circulating and dysregulated inflammatory biomarkers; which in turn is associated with abnormal clot formation. Methods Here, we investigate the correlation between abnormal blood clotting, using thromboelastography (TEG), clot ultrastructure using scanning electron microscopy (SEM) and the presence of a dysregulated inflammatory cytokine profile, by examining various circulating biomarkers. Results Our results show that many biomarkers, across TEG, cytokine and lipid groups, were greatly dysregulated in the T2DM sample. Furthermore, our T2DM sample’s coagulation profiles were significantly more hypercoagulable when compared to our heathy sample, and ultrastructural analysis confirmed a matted and denser clot structure in the T2DM sample. Conclusions We suggest that dysregulated circulating molecules may in part be responsible for a hypercoagulable state and vascular dysfunction in the T2DM sample. We propose further that a personalized approach could be of great value when planning treatment and tracking the patient health status after embarking on a treatment regimes, and that looking to novel inflammatory and vascular biomarkers might be crucial. Electronic supplementary material The online version of this article (10.1186/s12933-019-0870-9) contains supplementary material, which is available to authorized users.

Immunologists have recently taken note of the fact that a host not only resists infection, but also exhibits a capacity to manage the pathology associated with such infection – a concept referred to as tolerance. Here we explore how the tolerance/resistance (T/R) framework can be implemented within an oncological context and explore a number of implications. In particular, the T/R framework distinguishes between pathology manifesting from extensive tumor burden, versus cancers intrinsically expressing a more pathogenic phenotype. Consequently, the T/R framework provides novel methodology in studying the nature of cancer pathology and for marker identification. Additionally, this framework may aid in redefining the therapeutic end point under suitable circumstances: establishing cancer as a chronic, manageable disease.

Parkinson’s disease (PD) is a well-known neurodegenerative disease with a strong association established with systemic inflammation. Recently, the role of the gingipain protease group from Porphyromonas gingivalis was implicated in Alzheimer’s disease and here we present evidence, using a fluorescent antibody to detect gingipain R1 (RgpA), of its presence in a PD population. To further elucidate the action of this gingipain, as well as the action of the lipopolysaccharide (LPS) from P. gingivalis, low concentrations of recombinant RgpA and LPS were added to purified fluorescent fibrinogen. We also substantiate previous findings regarding PD by emphasizing the presence of systemic inflammation via multiplex cytokine analysis, and demonstrate hypercoagulation using thromboelastography (TEG), confocal and electron microscopy. Biomarker analysis confirmed significantly increased levels of circulating proinflammatory cytokines. In our PD and control blood analysis, our results show increased hypercoagulation, the presence of amyloid formation in plasma, and profound ultrastructural changes to platelets. Our laboratory analysis of purified fibrinogen with added RgpA, and/or LPS, showed preliminary data with regards to the actions of the protease and the bacterial membrane inflammagen on plasma proteins, to better understand the nature of established PD.

Background To date, no definitive waist circumference (WC) cut-off values for abdominal obesity (AO) have been established for sub-Saharan Africa, including Botswana. Therefore, the classification of AO among these populations is based on European values. For accurate diagnosis of the metabolic syndrome (MetS), cut-off values reflective of the population investigated must be used. Objective The study was an attempt to determine optimal cut-off values for AO among Batswana adults. Methods The receiver operating characteristic curve was used to determine the optimal cut-off values for predicting at least two other risk factors of the MetS. Data were used from a descriptive cross-sectional study employing a complex multi-stage cluster sampling. Demographic and anthropometric measurements (weight and height, waist and hip circumferences), blood pressure, and blood glucose, triglycerides, high-density lipoprotein cholesterol and total cholesterol levels were collected from 384 men and 416 women in Gaborone and the surrounding villages. Results The ability of waist circumference to predict at least two other risk factors of the MetS gave cut-off values of ≥ 91.0 cm (sensitivity 69.1% and specificity of 90.8%, area under the curve 0.85) for men and ≥ 82.3 cm (sensitivity of 88.6% and specificity of 58.9%, area under the curve of 0.76) for women. Conclusions There is a difference between the cut-off values for Europeans with those determined for Batswana adults. Inconsistencies in cut-off values used have the potential for undesirable consequences for cardiovascular risk stratification and prioritisation of preventative strategies for AO and the MetS. The need to determine population-, ethnic- and gender-based cut-off values for AO for Batswana adults has never been more paramount.

Sutherlandia frutescens is a plant that is endemic to South Africa and is traditionally used for the treatment of cancer and many other ailments. Although previous studies have shown S. frutescens to exert anti-proliferative and apoptotic effects in human mammary adenocarcinoma- and leukemia cell lines, its potential cytotoxic effects on colon cancer cells have not yet been established. Moreover, limited information is available elucidating the major signaling pathways involved upon exposure to the herbal extract. The aim of this study was therefore to assess the cytotoxic effect of S. frutescens on the colon cancer cell line CaCo2, to investigate molecular role players of apoptosis and to assess the involvement of the PI3-K survival pathway. CaCo2 cells exposed to ethanolic extracts of S. frutescens showed significant decreased cell viability, indicated by reduced MTT reductive capacity, increased pyknosis as well as loss in cellular membrane integrity. Western blot analysis revealed a down-regulation in the PI3-K and Akt phosphorylation, a decrease in forkhead transcription factor (FKHR) phosphorylation as well as a concomitant induction of apoptosis. This study demonstrates that Sutherlandia treatment attenuates proliferation of colon cancer cells in vitro by the disruption of the key molecules in the PI-3K pathway thereby inducing apoptosis.

Globally, breast cancer continues to be a major concern in women's health. Lifestyle related risk factors, specifically excess adipose tissue (adiposity) has reached epidemic proportions and has been identified as a major risk factor in the development of breast cancer. Dysfunctional adipose tissue has evoked research focusing on its association with metabolic-related conditions, breast cancer risk and progression. Adipose dysfunction in coordination with immune cells and inflammation, are responsible for accelerated cell growth and survival of cancer cells. Recently, evidence also implicates adiposity as a potential risk factor for chemotherapy resistance. Chemotherapeutic agents have been shown to negatively impact adipose tissue. Since adipose tissue is a major storage site for fatty acids, it is not unlikely that these negative effects may disrupt adipose tissue homeostasis. It is therefore argued that fatty acid composition may be altered due to the chemotherapeutic pharmacokinetics, which in turn could have severe health related outcomes. The underlying molecular mechanisms elucidating the effects of fatty acid composition in adiposity-linked drug resistance are still unclear and under explored. This review focuses on the potential role of adiposity in breast cancer and specifically emphasizes the role of fatty acids in cancer progression and treatment resistance.

Background: Although roll-out of combined anti-retroviral treatment (cART) has blunted HIV-AIDS onset, studies show increased development of cardiovascular diseases (CVD) in HIV-infected individuals. This study aimed to identify changes in immune cells (T cells, monocyte subsets) and determine their relationship to: (a) classical markers of HIV progression (CD4 count, viral load), (b) immune activation status and coagulation, and (c) traditional lipid profile/subclasses. Methods: Eighty participants were recruited (Worcester, South Africa) and fasted blood collected to evaluate: a) traditional lipid profile, b) immune markers, c) monocyte subpopulations (non-classical, intermediate, classical) by flow cytometry together with tissue factor (marker: thrombus formation) and CD38 (marker:immune activation) expression on CD4 and CD8 T cells. Classical regulatory T cells (Treg) with activation markers (glycoprotein A repetitions predominant [GARP], special AT-rich sequence-binding protein 1) were assessed together with high-and low-density lipoprotein subclasses (Lipoprint). Findings: This study revealed four key findings in HIV-positive patients: a) co-expression of a coagulation marker (tissue factor) together with immune activation on CD4 and CD8 T cells (irrespective of cART), b) Treg cell activation and upregulated GARP contributing to persistent immune activation, c) Pro-atherogenic monocyte subset expansion; and d) Lipopolysaccharide binding protein (LBP) as a key modulator mediating immunometabolic perturbations. Interpretation: These findings alert to the future clinical management of HIV-positive patients and highlight the need for earlier therapeutic interventions to address chronic inflammation, immune activation and LBP-mediated lipid subclass effects. This strategy should decrease coagulation and lower CVD risk. Funding Statement: This work was supported by the Medical Research Council and Stellenbosch University [MFE]. Declaration of Interests: None declared. Ethics Approval Statement: This study complies with the Declaration of Helsinki and ethical approval was obtained from the Human Research Ethics Committee of Stellenbosch University and the Department of Health (Western Cape Government, South Africa). Prior to the study, all participants were informed about procedures and consent forms were signed by all.

Since cancer shares the same molecular machinery as the host, most therapeutic interventions that aim to target cancer would inadvertently also adversely affect the host. In addition, cancer continuously evolves, streamlining its host-derived genome for a new single-celled existence. In particular, short-term clinical success observed with most antineoplastic therapies directly relate to the fact that cancer is constantly evolving. However, the clonal evolution of cancer occasionally also render cancer cells uniquely susceptible to therapeutic interventions, as is exemplified by the clinical relevance of synthetic lethality. Synthetic lethality describes a situation where the simultaneous loss of function in two genes results in lethality, but where a loss of function in either single gene is tolerated. This observation suggests that the evolution of cancer, usually seen as a major clinical challenge, may also afford a key opportunity in lowering on-target toxicities accosted with chemotherapy. As an example, by subjecting cancer to specific selection regimes, cancer can in effect be placed on evolutionary trajectories leading to the development of “targetable” phenotypes such as synthetic lethal interactions. However, such a selection regime would have to overcome a range of obstacles such as on-target toxicity and the selection of an evolvable trait. Since the majority of cancer evolution manifests as a loss of function, we suggest that the induction of auxotrophic phenotypes (i.e., where an organism lose the ability to synthesize specific organic compounds required for growth and thus become dependent on it from dietary sources) may represent an attractive therapeutic option. As an example, animals can obtain vitamin C either by de novo synthesis or from their diet. However, since the maintenance of synthetic pathways is costly, such pathways are often lost if no longer necessary, resulting in the organism being auxotrophic toward the dietary compound. Similarly, increasing the maintenance cost of a redundant pathway in cancer cells is likely to select for clones that have lost such a redundant pathway. Inhibition of a pathway, while supporting the activity of a compensating pathway, may thus induce auxotrophism in cancer cells but not in genomic stable host cells.

Background In South Africa, not much is known about MetS in farm working communities. This study aimed to describe the prevalence of the MetS in a farm working population from the Boland winelands district of the Western Cape, South Africa. Methods A cross-sectional study was followed among farm workers (aged 20–60 years) from surrounding wine estates. The questionnaires used described socio-demographic status, ethnic background, alcohol consumption, smoking, exercise and daily medication. Anthropometric assessments were performed and blood pressure measurements taken prior to blood sampling for serum insulin, glucose and fasting lipogram profiles. Results The prevalence of the MetS was higher in women (46.3 vs 29.3%). Both men and women in the MetS group had a significantly higher waist circumferences (WC; p

Activation of the immune system is metabolically costly, yet a hallmark of an infection is a reduction in appetite with a subsequent reduction in metabolite provision. What is the functional value of decreasing nutrient intake when an infection imposes large demands on metabolic parameters? Here, we propose that sickness-associated anorexia (SAA) upregulates the ancient process of autophagy systemically, thereby profoundly controlling not only immune- but also nonimmune-competent cells. This allows an advanced impact on the resolution of an infection through direct pathogen killing, enhancement of epitope presentation and the contribution toward the clearance of noxious factors. By rendering a 'free meal,' autophagy is thus most fundamentally harnessed during an anorexic response in order to promote both host tolerance and resistance. These findings strongly suggest a reassessment of numerous SAA-related clinical applications and a re-evaluation of current efforts in patient care.

Protease inhibitors (PIs) is linked to adverse metabolic/anthropometric derangements, increasing the risk for cardiovascular diseases (CVD) onset in HIV-infected individuals. As limited information...

Background: Both wheat pasta and dry beans have low glycaemic indices (GIs). However, it has been shown that several factors, including method of processing, may influence the GI of a food. Extrusion of dry beans is a relatively new dry cooking process and provides a convenient alternative to the ingestion of dry beans.

Polymorphic N -acetyltransferase genes ( NAT1 and NAT2 ) determine rapid or slow acetylation phenotypes, which are believed to affect cancer risk related to environmental exposure. Black South Africans have a unique incidence pattern of environment-related cancers, but genetic characteristics of this population are mostly unknown. In this study, we compared NAT1 and NAT2 allele distributions in 101 Black South Africans and 112 UK Caucasians. Frequencies of the rapid alleles were significantly higher in Black South Africans for both NAT1 and NAT2 . Putative rapid NAT1 genotypes due to the presence of either NAT1 ∗ 10 or NAT1 ∗ 11 were found in 74.3% of Black South Africans (only NAT1 ∗ 10 ) and 42.0% of UK Caucasians ( P NAT2 analysis showed that the presence of NAT2 ∗ 4 , NAT2 ∗ 12A , NAT2 ∗ 12B , NAT2 ∗ 12C , and NAT2 ∗ 13 alleles provided significantly higher ( P =0.0001) frequency of rapid acetylation genotypes among Black South Africans (60.4%) than in the Caucasian group (33.9%). The rapid acetylation genotype in Caucasians usually depended on the NAT2 ∗ 4 allele presence. The significant differences in N -acetylation genotypes can be among the factors determining a distinctive cancer morbidity and mortality pattern observed in Black South Africans. Both further genetic characterization of different populations and development of preventive strategies adopted for ethnicities with different genetic backgrounds are needed to deal adequately with the emerging health care problems in developing multiethnic societies.

Nutritional status and risk factors for chronic diseases, including plasma fibrinogen and its determinants, of Africans in the Northwest Province of South Africa, have been studied in a cross-sectional survey. A representative sample of 1854 "apparently healthy" African men and women volunteers aged 15 years and older was recruited from 37 randomly selected sites throughout the Province and stratified for level of urbanisation. Information was collected using validated and culture-sensitive questionnaires. Fasting blood samples were drawn, and all measurements were done with standardised methodology using appropriate equipment, procedures, and controls. Fibrinogen concentration was measured in citrated plasma with the method of Clauss, using the ACL200 automated system and the international fibrinogen standard. The results revealed a population with a high mean plasma fibrinogen (3.17+/-1.10 g/L for HIV-negative men and 3. 64+/-1.12 g/L for HIV-negative women). Factors known to influence plasma fibrinogen, such as age, gender, smoking habit, and physical activity, were also observed in this population. Young rural men and women had the lowest fibrinogen level. Nasal snuff taking and HIV infection did not influence fibrinogen concentration. Multivariate analyses revealed that lower plasma fibrinogen was associated with low to normal body mass index in women, and with dietary intakes compatible with prudent dietary guidelines in men and women (low intakes of animal protein; trans fatty acids and higher intakes of plant protein; dietary fibre, vitamin E, and iron, and a high dietary P/S ratio). Subjects in the higher quartiles of plasma fibrinogen had significantly lower iron, vitamin E, and vitamin B6 (women) status. Increases in fibrinogen were associated with significant increases in serum lipids. Both under- and overnutrition seem to be associated with high plasma fibrinogen. It is concluded that overall nutritional status, possibly in addition to specific nutrients (and foods), influences plasma fibrinogen.

Genetic polymorphisms for apolipoprotein E (apo E) and methylenetetrahydrofolate reductase (MTHFR) are believed to modulate risk of coronary heart disease (CHD) acting through regulation of lipid and homocysteine metabolism, respectively. The distributions of apo E and MTHFR alleles in Black South Africans, a population with a low CHD incidence, and UK Caucasians from the Cambridge area, with a higher CHD incidence, were therefore compared. Clinically healthy volunteers (207), including 107 UK Caucasians from the Cambridge area and 100 Black South Africans, participated in the study. Apo E and MTHFR genotypes were determined in all of them. Analyses for serum total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides and plasma fibrinogen were carried out in 65 UK Caucasians and 60 Black South Africans. The apo E epsilon4 allele, which is associated with elevated CHD risk, was present in 48% of Black South Africans compared to 20.8% of Caucasians (P < 0.0001); however, both total and LDL cholesterol levels in Black South Africans were 18-32% lower than in Caucasians with similar apo E genotypes. Hyperhomocysteinemia-causing MTHFR 677T variant was detected in only 20% of Black South Africans (no homozygotes) versus 56% of Caucasians with 12% homozygotes (P

Although numerous studies have shown that certain long chain fatty acids can induce apoptosis in cancer cells, the molecular mechanisms for this phenomenon are still poorly elucidated. The phosphoinositide 3-kinase (PI3-kinase) signaling pathway plays a pivotal role in the regulation of cell growth and can also contribute to tumorigenesis and cancer progression. The aims of the present study were three fold: (i) to investigate the potential chemopreventative/antiproliferative effect of various fatty acids in colon cancer cells (CaCo-2 cells) and normal colon epithelium cells (NCM460 cells); (ii) to investigate the mechanisms by which incubation with various fatty acids influences the PI3-kinase pathway in CaCo-2 cells; and (iii) to evaluate apoptosis in our cell model. Although all the fatty acids increased the viability of normal (NCM460) cells, only docosahexaenoic acid (DHA) significantly reduced cell viability and induced apoptosis in the cancer (CaCo-2) cells. Our results indicate that DHA is an effective chemotherapeutic agent to induce apoptosis in cancer cells and that this effect is mediated by the PI3-kinase signaling pathway.

This paper briefly reviews the role of dietary fats (lipids) in human nutrition, summarises the contribution to the symposium on fats and oils during the 2000 South African Nutrition Congress, and examines the present recommendations and controversies regarding fat intake, in order to examine whether in a developing country such as South Africa, dietary fat recommendations to consumers should be more explicit, specific and detailed. It is concluded that to reach “optimal” intakes, some groups in South Africa (e.g. rural blacks) should increase intakes, while those at risk for cardiovascular disease should lower intakes. It is suggested that all South Africans over the age of 2 years should aim for an intake in which fat provides approximately 30% of total energy. To meet the guidelines that more omega-3 (ω-3), proportionally more monounsaturated fatty acids and less trans and saturated fatty acids should be eaten, alternative sources of and for these fatty acids in the South African diet should be...