Gloudina M. Hon

Derivation and validation of a waist circumference optimal cutoff for diagnosing metabolic syndrome in a South African mixed ancestry population

metabolic syndrome in a South African mixed ancestry population T.E. Matsha ⁎, M.S. Hassan , G.M. Hon , D.J. Soita , A.P. Kengne , R.T. Erasmus c,1 a Department of Biomedical Technology, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa b Department of Nursing and Radiography, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa c Division of Chemical Pathology, Faculty of Health Sciences, University of Stellenbosch, Cape Town, South Africa d NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council, Cape Town, South Africa e Department of Medicine, University of Cape Town, Cape Town, South Africa

Immune cell membrane fatty acids and inflammatory marker, C-reactive protein, in patients with multiple sclerosis

Measurement of fatty acids in biological fluids and cell membranes including leucocytes from multiple sclerosis patients is inconsistent. The objective of the present study was to investigate the fatty acid composition within the different membrane phospholipid fractions in peripheral blood mononuclear cells in multiple sclerosis patients, and correlate with severity of neurological outcome as measured by the Kurtzke Expanded Disability Status Scale and Functional System Scores. The fatty acid composition of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin and phosphatidylinositol phospholipids in the peripheral blood mononuclear cells of twenty-six multiple sclerosis and twenty-five control subjects were measured by GC, and C-reactive protein was measured in all subjects. The elongation product of 20 : 4n-6, 22 : 4n-6, was significantly decreased in membrane phosphatidylethanolamine and phosphatidylserine in multiple sclerosis patients (P = 0.01 and P = 0.03 respectively), and correlated inversely with severity of disease and C-reactive protein. Also an inverse correlation was observed between the C-reactive protein and membrane phosphatidylcholine and phosphatidylserine 20 : 4n-6. Cultural and ethnic differences, as well as dietary variability, especially in a diseased state have been implicated in the differences observed in the fatty acid composition in peripheral blood mononuclear cell membranes of patients with multiple sclerosis. The present results suggest that the disease state may in part explain the reported inconsistencies in fatty acid levels in multiple sclerosis patients.

Optimal Waist-to-Height Ratio Values for Cardiometabolic Risk Screening in an Ethnically Diverse Sample of South African Urban and Rural School Boys and Girls

Background The proposed waist-to-height ratio (WHtR) cut-off of 0.5 is less optimal for cardiometabolic risk screening in children in many settings. The purpose of this study was to determine the optimal WHtR for children from South Africa, and investigate variations by gender, ethnicity and residence in the achieved value. Methods Metabolic syndrome (MetS) components were measured in 1272 randomly selected learners, aged 10–16 years, comprising of 446 black Africans, 696 mixed-ancestry and 130 Caucasians. The Youden’s index and the closest-top-left (CTL) point approaches were used to derive WHtR cut-offs for diagnosing any two MetS components, excluding the waist circumference. Results The two approaches yielded similar cut-off in girls, 0.465 (sensitivity 50.0, specificity 69.5), but two different values in boys, 0.455 (42.9, 88.4) and 0.425 (60.3, 67.7) based on the Youden’s index and the CTL point, respectively. Furthermore, WHtR cut-off values derived differed substantially amongst the regions and ethnic groups investigated, whereby the highest cut-off was observed in semi-rural and white children, respectively, Youden’s index0.505 (31.6, 87.1) and CTL point 0.475 (44.4, 75.9). Conclusion The WHtR cut-off of 0.5 is less accurate for screening cardiovascular risk in South African children. The optimal value in this setting is likely gender and ethnicity-specific and sensitive to urbanization.

Erythrocyte membrane fatty acids in patients with multiple sclerosis

Background Reports on fatty acids levels in multiple sclerosis remain inconclusive. Objective To determine the erythrocyte membrane fatty acid levels in multiple sclerosis patients and correlate with Kurtzke Expanded Disability Status Scale. Methods Fatty acid composition of 31 multiple sclerosis and 30 control individuals were measured by gas chromatography. Results The membrane phosphatidylcholine C20:4n – 6 concentration was lower in the multiple sclerosis patients when compared to that of the control group, P = 0.04 and it correlated inversely with the EDSS and FSS. Conclusion Decrease in C20:4n – 6 in the erythrocyte membrane could be an indication of depleted plasma stores, and a reflection of disease severity.

Three-year's changes in glucose tolerance status in the Bellville South cohort: rates and phenotypes associated with progression.

AIMS To determine the phenotypes associated with progression to type 2 diabetes or worsening in glucose tolerance during a 3-year follow-up of a community-based cohort in Cape Town, South Africa. METHODS A total of 198 eligible subjects (72.3% women) aged 55.2 years, from the Bellville-South community were followed-up between 2008 and 2011. Baseline and follow-up data collections included glucose tolerance status, anthropometric, blood pressure, lipids, insulin, γ-glutamyltransferase, cotinine, creatinine and HbA1c. Progression in glucose tolerance status at 3-year was the composite of new-onset diabetes and any worsening in glucose tolerance status. RESULTS The cumulative incidence of progression in glucose tolerance status was: 16.2% (32 participants including 11 with new-onset diabetes), and increased in a stepwise fashion with the number of components of metabolic syndrome (MetS). In age and sex-adjusted logistic regression analyses, MetS [odd ratio: 3.08 (95% CI: 1.34-7.10)], HbA1c [5.26 (1.94-14.24)], HDL-cholesterol [0.05 (0.01-0.33)], γ-glutamyltransferase [1.99 (1.07-3.67)], triglycerides [1.71 (1.13-2.58)] and total/HDL-cholesterol [1.45 (1.08-1.93)] were significant predictors of progression, while borderline effects were observed for baseline glucose and diastolic blood pressure. Markers of adiposity were mostly stable or improved among non-progressors during follow-up, but deteriorated significantly among progressors, resulting in significant statistical interactions. CONCLUSIONS High rates of deterioration of glucose status over time were found in our population, with nearly one-fifth of them acquiring a glucose tolerance worse status within a very short follow-up. Our study extends to this setting the well-known utility of phenotypes of MetS single or in combination, in predicting worsening in glucose tolerance status.

Low prevalence of human herpesvirus-6 and varicella zoster virus in blood of multiple sclerosis patients, irrespective of inflammatory status or disease progression

Herpesviruses, including human herpesvirus-6 and varicella zoster virus, have been implicated in the disease aetiology of multiple sclerosis. These viruses are capable of reactivation, reminiscent of the relapsing-remitting nature of multiple sclerosis. However, viral DNA has also been reported present in healthy controls, often at similar prevalence rates. This study aimed to determine whether prevalence could be associated with different stages of activity of the disease as well as the inflammatory status of the patients. Polymerase chain reaction assays were used to screen for human herpesvirus-6 and varicella zoster virus DNA in blood from 31 Caucasian patients with multiple sclerosis and 30 healthy age, sex and race matched control subjects. The patients were screened for inflammation using C-reactive protein as a marker and were also categorized according to their remitting/relapsing status. Results were positive for human herpesvirus-6 in blood from only one patient (3.2%) and human herpesvirus-6 DNA was not present in any control subjects. Varicella zoster virus was not detected in either the patients or control subjects. Similar to some other studies we saw an absence or very low viral positivity in blood from both patients and controls. These findings were irrespective of relapse episodes, increased inflammatory status or duration of the disease. Results therefore do not support a causative role for either human herpesvirus-6 or varicella zoster virus in the disease aetiology of multiple sclerosis, but rather that prevalence in patients may be linked to that of the general population.

Multiple sclerosis-associated retrovirus and related human endogenous retrovirus-W in patients with multiple sclerosis: A literature review

Human endogenous retrovirus-W and the closely related multiple sclerosis-associated retrovirus have been associated with neuro-inflammatory diseases including multiple sclerosis. However, retroviral expression has been reported in brain tissue from healthy subjects as well. In addition, no consensus has been reached on the endogenous/exogenous status of multiple sclerosis-associated retrovirus, which also needs clarification. Therefore, the purpose of this study was to systematically review the published data available on the viruses investigated in patients with multiple sclerosis and to evaluate their hypothesized role as contributing factors to the disease etiology. Evidence suggests that both retroviruses may be endogenous to humans and that failure to suppress viral activity may not be restricted to patients with multiple sclerosis and therefore an unlikely cause of the disease.

Peripheral Blood Mononuclear Cell Membrane Fluidity and Disease Outcome in Patients with Multiple Sclerosis

Immune cell membrane lipids are important determinants of membrane fluidity, eicosanoid production and phagocytosis and fatty acid metabolic abnormalities have been reported in immune cells from patients with multiple sclerosis. The aim of this study was to investigate the relationship between peripheral blood mononuclear cell membrane fluidity, permeability status, and disease outcome as measured by the Kurtzke expanded disability status scale. Phospholipids, fatty acids and cholesterol composition in peripheral blood mononuclear cells from 26 patients diagnosed with multiple sclerosis and 25 healthy control subjects were determined by colorimetric assay, gas chromatography and enzymatic assays, respectively. Membrane fluidity was calculated according to previously established formulae and correlated with C-reactive protein and the Kurtzke expanded disability status scale. There were no significant differences in membrane lipids in peripheral blood mononuclear cells from patients and controls. However, correlation studies showed lipid metabolic abnormalities, which were reflected in significant correlations between membrane fluidity as measured by both its fatty acid and phospholipid compositions, and the functional system scores. C-reactive protein showed positive correlations with phosphatidylcholine, phosphatidylserine, phosphatidylinositol and total phospholipids in membranes from control subjects. Metabolic abnormalities, as well as correlations between membrane fluidity and the functional system scores, suggested the involvement of these immune cell membranes in the disease progression. Furthermore, the changed relationship between membrane phospholipids and C-reactive protein, which has been shown to correlate with infectious episodes and clinical relapse, could be an indication of immune cell dysfunction in patients with multiple sclerosis.

Assessment of Epstein-Barr virus in blood from patients with multiple sclerosis

Viruses such as Epstein-Barr virus (EBV) which can establish latent infections in the central nervous system or the immune system have been associated with chronic neurological disorders, including multiple sclerosis. Results vary, therefore the aim of this study was to investigate the presence of EBV using both viral DNA and antibody screening techniques, using PCR and ELISA assays respectively, to evaluate viral presence in blood from control subjects and patients with multiple sclerosis. Viral gene sequences for latent proteins EBNA-1 and LMP-1 and lytic gene BamH1-W were present equally in both patients and controls (<7%). Anti-EBV-VCA IgG positive cases were present in >99% of all study subjects, and anti-EBV-VCA IgG immune status ratio showed a near-significant positive correlation with the EDSS in patients with multiple sclerosis. In contrast, Anti-EBV-VCA IgM positive cases were significantly increased in patients (controls: 23.3%; patients; 41.9%; P = 0.046). The IgM to IgG immune status ratio was near-significantly higher in patients with relapse episodes in the year preceding blood sampling (P = 0.058). Results from this and previous studies have shown higher prevalence rates for EBV evaluating anti-EBV IgM positive cases against viral DNA positive cases. Also, IgM, an innate immune response, showed an association with relapse episodes, suggesting viral re-activation as a contributing factor to these relapses.

Membrane saturated fatty acids and disease progression in Multiple Sclerosis patients

The risk of developing multiple sclerosis is associated with increased dietary intake of saturated fatty acids. We determined the fatty acid composition within the different phospholipid fractions of red blood and peripheral blood mononuclear cell membranes of 31 patients diagnosed with multiple sclerosis and 30 healthy control subjects using gas chromatography. Individual saturated fatty acids were correlated with the severity of neurological outcome as measured by the Kurtzke Expanded Disability Status Scale. Significant increases were found in multiple sclerosis peripheral blood mononuclear cell membrane sphingomyelin C14:0 and phosphatidylinositol C22:0. In the peripheral blood mononuclear cell membranes, C22:0 and C24:0 showed positive correlations, while C14:0, C16:0 and C20:0 showed inverse correlations with the Functional System Scores. In conclusion, this study is in accordance with previous studies that have shown an increase in shorter long-chain SATS in MS patients. In addition, this study also showed that higher C14:0 and C16:0 reflected better disease outcome as demonstrated by the inverse correlation with the EDSS and FSS. We have also characterized the specific SATS, that is, long-chain SATS that may increase the risk of developing MS.