Gershwin Davis

Sialic acid, homocysteine and CRP: potential markers for dementia.

To investigate whether sialic acid could discriminate between healthy age matched controls and patients with dementias of the Alzheimers type (AD), and pure vascular dementia (VaD). 27 patients and 51 controls were administered the Mini-Mental State Examination (MMSE) and had blood analyzed for levels of total sialic acid, total homocysteine (tHcy), and C-reactive protein (CRP). Significant differences were found between the mean MMSE scores for patients with dementia compared with controls. Sialic acid levels were significantly higher in patients with AD compared with controls and homocysteine levels were higher in VaD. Sialic acid levels discriminated between patients with dementia of the Alzheimers type and healthy controls only. The MMSE could discriminate between controls and patients with dementia but not between the subtypes and homocysteine was significant for patients with VaD.

Flow injection analysis of lactose using covalently immobilized β-galactosidase, mutarotase, and glucose oxidase/peroxidase on a 2-fluoro-1-methylpyridinium salt-activated fractogel support

Milk samples were analyzed for their lactose content using flow injection analysis and incorporating immobilized beta-galactosidase or beta-galactosidase/mutarotase and glucose oxidase/peroxidase bioreactors. These enzymes were immobilized, under mild conditions, on to a 2-fluoro-1-methylpyridinium salt-activated Fractogel support. The use of a phosphate buffer (0.15 M) was found to facilitate the rapid mutarotation of alpha-D-glucose and hence could obviate the need for the more expensive mutarotase. The chromogenic agents of choice for monitoring the reaction were 3-methyl-2-benzothiazolinone hydrazone and 3-dimethylaminobenzoic acid. Linearity was observed over the concentration range 16-160 micrograms/ml using lactose standards (r = 0.996). Between 30 and 40 milk samples/h can be analyzed. Comparisons are made with existing HPLC and alkaline methylamine methods for a range of milk matrices. The FIA method consistently gives the lowest standard deviations and coefficient of variation for the various milk matrices analyzed.

Potential biomarkers for dementia in Trinidad and Tobago

Biomarkers that could possibly discriminate between healthy controls and patients with dementias of the Alzheimers type (AD) and vascular dementia (VaD) were investigated. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition TR (DSM IV TR) was used to diagnose for dementia in Trinidad. Healthy seniors greater than 60 years old were controls. All participants were administered the Mini-Mental State Examination (MMSE) and had blood analyzed for levels of C-reactive protein (CRP), total homocysteine (tHcy) and microglial antibodies (MgAb). Plasma tHcy was determined on the Abbot AxSym, serum CRP concentrations were measured using the Tina-Quant sCRP (Latex) high sensitive immunoturbidimetric assay and serum MgAb were examined on frozen rat brain sections. The study was carried out on 29 patients that fulfilled the inclusion criteria and 46 controls. Of the patients 65.5% had AD and 34.5% had VaD. Significant differences were found between the mean MMSE scores of the different types of dementias and controls. MgAb presence as well as tHcy were able to distinguish between controls and dementia of the AD and VaD type, respectively. The MMSE is a good discriminative tool for dementias. Serum MgAbs are a possible biomarker for Alzheimer disease pathology and tHcy is elevated in patients with vascular dementia.

Improved spectrophotometric determination of lactose in milk using flow-injection analysis

Abstract Milk samples were analysed spectrophotometrically for their lactose content using flow-injection analysis. The methodology is based on the carmine colour that develops (λMax = 540 nm) when lactose reacts with alkaline methylamine (pH 12.7). Lactose concentrations as low as 0.6 mg ml−1 can be readily detected and up to 40 samples can be analysed per hour. Excellent correlations (r > 0.999) are obtained when the results are compared with the batch and liquid chromatographic methods for lactose determination. Interference from maltose, if present, should be eliminated by pretreatment with maltase.

β-Galactosidase covalently immobilized on fractogeL derivative: preparation, bioreactor flow kinetics, solvent effects and stability

Abstract β-Galactosidase has been successfully immobilized via covalent linkages to a 2-fluoro-N-methylpyridinium Fractogel support. The method of immobilization proved to be very mild and facile. Detailed investigations of the flow kinetics, pH profile, temperature effects and thermal stability were performed on a plug flow β-galactosidase bioreactor. The effects of various water-miscible organic solvents, such as methanol, ethanol, propan-1-ol, glycerol, dimethyl sulphoxide, acetonitrile and tetramethyl urea, on the kinetics and stability of this bioreactor were also investigated. The alcoholic solvents, with the exception of ethanol, enhanced the rate of liberation of o-nitrophenol from the substrate ONPG, whereas the other solvents decreased the rate of liberation of o-nitrophenol.

Combining Flow Injection Analysis and Immobilized Enzymes for Rapid and Accurate Determination of Serum Glucose

Abstract Serum samples were analysed for their glucose content using a co-immobilized glucose oxidase-peroxidase bioreactor and flow injection analysis. The enzymes were covalently coupled to a 2-fluoro-1-methylpyridinium activated support under mild and facile conditions. Optimum activity was achieved when a total of 0.72 mg protein per mL of support and in the ratio of 1.8 to 1.0 (glucose oxidase :peroxidase, in terms of their activities) was offered for coupling. The immobilized enzyme showed excellent storage stability at 4O °C retaining up to 95% of its initial activity after 60 days.

The importance of diabetes health education in developing countries.

Measurement of HbA1c remains the cornerstone of management of glycaemic control in people with diabetes, being the major factor in assessing an individual’s risk of microvascular complications. The need for standardization of measurements, particularly to allow comparison of individual values with the Diabetes Control and Complications (DCCT) and the UK Prospective Diabetes Study (UKPDS) results, and for service audit, benchmarking and quality assurance, remains a crucial issue of world-wide interest and importance. In the UK in 2000, experts agreed that within the limits of knowledge and technical expertise available at the time, as a first step towards standardization, harmonization of results could be achieved by using HbA1c assays which were DCCTtraceable and which reported results comparable to DCCT and UKPDS values [1,2]. Methods currently used to measure HbA1c in clinical practice achieve this by using calibration material whose values have been assigned by the US National Glycohemoglobin Standardisation Program (NGSP). Since the publication of this agreement as a Consensus Statement, there has been a significant shift in the UK to DCCT-aligned assays. Information from the external quality assessment schemes confirms that currently around 80% of UK laboratories participating in the scheme use DCCT-aligned methods. Following similar discussions in the USA, under the auspices of the NGSP, a similar shift has occurred: 62% of laboratories report DCCT-traceable results. The UK Consensus Statement recognized that this procedure was a pragmatic first step and that formal standardization required much more work. The NGSP Clinical Advisory Committee met recently to discuss how to move forward. The signatories to this letter were invited to attend as representatives of the UK Consensus Statement Group (S.M.M.), the International Diabetes Federation (P.D.H.), UKPDS central laboratory (S.E.M.) and The International Federation of Clinical Chemistry (W.G.J.). The International Federation of Clinical Chemistry (IFCC) has developed a specific HbA1c method which has been accepted internationally as the IFCC official Reference Method. Primary reference materials are currently being investigated in the hope that they could be used world-wide as a standardization tool. Clearly, the development of a valid chemical standard is highly desirable. After initial difficulties, in recent unpublished studies, it has been found that the regression line and line obtained between NGSP values and the IFCC Reference Method are now almost parallel. Results obtained with the IFCC standard are approximately 1.5–2.0% HbA1c lower than with NGSP, as might be expected from non-specific interference measured by the method used in the DCCT. Validation of the IFCC standard material continues. From the end of 2003, an EU Directive on the use of in vitro diagnostic equipment (IVD Directive; Directive 98/9/EC) will require that ‘the traceability of values assigned to calibrators and/or control materials must be assured through available reference measurement procedures and/or available reference materials of a higher order’ (Annex I–Essential Requirements. Part A. General Requirements, Clause 3). However, as the IFCC standard material is still under investigation, it would seem precipitous to recommend universal adoption of the IFCC calibration to achieve standardization of HbA1c results at the moment. Long-term evaluation of the stability of the IFCC reference method relationship to the DCCT/UKPDS assay must be ensured if clinicians are to have confidence in it. In addition, whilst it is vitally important in the future to have a chemically specific standardization anchor for HbA1c measurement, it remains equally important that expression of results remains linked to DCCT/UKPDS values. We would therefore strongly endorse for the time being the procedure for HbA1c harmonization described in the 2000 Consensus Statement. The position will be re-evaluated next year by the NGSP and the International Diabetes Federation.

Dementia prevalence in a population at high vascular risk: the Trinidad national survey of ageing and cognition

Objective To investigate the dementia prevalence in a country with high levels of cardiovascular risk factors Design and methods Older people in Trinidad are recognised to have particularly high levels of cardiovascular risk factors. We carried out a survey in a nationally representative sample of people aged ≥70 years using household enumeration. Dementia status was ascertained using standardised interviews and algorithms from the 10/66 schedule and age-specific prevalence were compared with identically defined output from the 10/66 surveys of 16 536 residents in eight other low-income and middle-income countries. Results Of 1832 participants (77.0% response rate), dementia was present in 442 (23.4%). Prevalences were 12.0% in persons aged 70–74 years, 23.5% at 75–79, 25.8% at 80–84, 41.3% at 85–89 and 54.0% in those aged ≥90 years. Prevalence ratios compared with averages from 10/66 surveys in these age groups were 2.2, 2.6, 1.6, 1.7 and 1.6, respectively, and were 2.7, 2.8, 1.7, 1.4 and 0.8, respectively, compared with previously published consensus estimates for the Latin American region. Dementia was significantly associated with reported stroke and diabetes in logistic regression models adjusted for sociodemographic status and other vascular risk factors (OR (95% CI) 4.40 (2.70 to 7.19) and 1.56 (1.20 to 2.03), respectively). Projected national numbers of people with dementia (18 206) were 70%–100% higher than those estimated using most recent regional consensus prevalences. Conclusion In a nation with high levels of vascular risk, dementia prevalence is higher than expected, particularly at the lower end of the 70+ age range. International prevalence projections may need to take into account risk status as well as age structures.

Measurement of neutrophil gelatinase-associated lipocalin (NGAL) in patients with non-communicable diseases: any additional benefit?

Abstract Aim: Chronic kidney disease (CKD) is one of the major complication from non-communicable diseases (NCD), such as diabetes or hypertension. We aimed to determine if routine measurement of neutrophil gelatinase-associated lipocalin (NGAL) in NCD patients could provide additional benefit for diagnosing kidney disease. Methods: Fasting serum NGAL, urea, creatinine, uric acid and albumin were measured in 298 NCD patients. Estimated glomerular filtration rate (e-GFR) was calculated using the CKD-EPI equation. Multiple linear regression modeling was used for analysis. Results: CKD patients have the highest levels of NGAL than the other NCD patients (p < 0.001). Although NGAL was significantly related to e-GFR, creatinine, urea and albumin in CKD-patients (p < 0.001) and not in the other NCD patients (p > 0.05), only serum creatinine predicted NGAL levels in CKD-patients (p < 0.001). Conclusion: NGAL level is best associated with serum creatinine only in patients with CKD and NGAL measurement may not be cost effective as a routine kidney function test in NCD patients in under-resourced economies.

Trinidad and Tobago. A decade of dementia research

In 2003, academic staff members at The University of the West Indies Faculty of Medical Sciences St Augustine Trinidad and Tobago combined their expertise to make strides in Alzheimers and Dementia research in Trinidad and Tobago. Dr. Nelleen Baboolal, Dr. Gershwin Davis and Professor Amanda McRae began developing a project that has produced significant results by examining not only the epidemiology of dementia, but the associated risk factors; caregiver burden and ultimately establishing biomarkers for the disease. This review is an account of our results from a decade of dementia research and how they are contributing toward mitigating the dementia tsunami in Trinidad and Tobago.