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1.
Cardiovasc J Afr ; 19(3): 141-4, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18568173

RESUMO

AIM: Ischaemia-modified albumin (IMA), as measured by the albumin-cobalt binding (ACB) test, has been cleared by the US Food and Drug administration as a biomarker to exclude the presence of myocardial ischaemia in patients. Although there are a number of published studies detailing the clinical utility of IMA, data on the biological variation of IMA are still lacking. In this study we determined the analytical and biological variance components of ischaemia modified albumin, and compared the distribution of IMA values in our patient population to those provided by the kit manufacturer. METHODS: IMA was determined once a week for five consecutive weeks on a cohort of healthy subjects using a colorimetric method, the A CB test on a Roche modular analyser. RESULTS: The analytical coefficient of variation (CV(A)) was 5%, and the within-subject (CV(I)) and between-subject (CV(G)) biological variations were 3 and 7%, respectively. Analysis of the repeated measures with gender and race (black and Caucasian) as between-subject factors, and weeks (1-5) as the within-subject factor showed that gender had no significant effect on circulating IMA concentrations (p = 0.3146), whereas race did have a significant effect (p = 0.0062). A significant (p = 0.0185) interaction was observed between gender and race. CONCLUSION: The ACB test could bring a new dimension to the care and management of patients with acute coronary syndrome. Further studies for normal population distributions by gender and ethnicity, and an optimum cut-off value appear to be required.


Assuntos
Cobalto , Isquemia Miocárdica/diagnóstico , Kit de Reagentes para Diagnóstico/normas , Albumina Sérica/metabolismo , Adulto , Negro ou Afro-Americano , Biomarcadores/sangue , Estudos de Coortes , Colorimetria/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/etnologia , Valor Preditivo dos Testes , Ligação Proteica , Valores de Referência , Reprodutibilidade dos Testes , Fatores Sexuais , População Branca
2.
Cardiovasc. j. Afr. (Online) ; 19(3): 141-144, 2008.
Artigo em Inglês | AIM (África) | ID: biblio-1260379

RESUMO

Aim : Ischaemia-modified albumin (IMA); as measured by the albumin-cobalt binding (ACB) testr; has been cleared by the US Food and Drug administration as a biomarker to exclude the presence of myocardial ischaemia in patients. Although there are a number of published studies detailing the clinical utility of IMA; data on the biological variation of IMA are still lacking. In this study we determined the analytical and biological variance components of ischaemia-modified albumin; and compared the distribution of IMA values in our patient population to those provided by the kit manufacturer. Methods : IMA was determined once a week for five consecutive weeks on a cohort of healthy subjects using a colorimetric method; the ACB testr on a Roche modular analyser. Results : The analytical coefficient of variation (CVA) was 5; and the within-subject (CVI) and between-subject (CVG) biological variations were 3 and 7; respectively. Analysis of the repeated measures with gender and race (black and Caucasian) as between-subject factors; and weeks (1-5) as the within-subject factor showed that gender had no significant effect on circulating IMA concentrations (p = 0.3146); whereas race did have a significant effect (p = 0.0062). A significant (p = 0.0185) interaction was observed between gender and race. Conclusion : The ACB testr could bring a new dimension to the care and management of patients with acute coronary syndrome. Further studies for normal population distributions by gender and ethnicity; and an optimum cut-off value appear to be required


Assuntos
Albuminas , Biodiversidade , Isquemia
3.
Cardiovasc. j. Afr. (Online) ; 19(5): 264-267, 2008.
Artigo em Inglês | AIM (África) | ID: biblio-1260389

RESUMO

Background : Amino terminal pro-B-type natriuretic peptide (NT-proBNP) is a sensitive marker of ventricular dysfunction. Exercise causes an increase in the secretion of NT-proBNP; and with myocardial ischaemia the increase is more pronounced. This increase has been found to improve the diagnostic sensitivity of the stress ECG in diagnosing myocardial ischaemia in subjects with normal ventricular function. Objective : To assess whether the change in NT-proBNP can be used to diagnose effort-induced myocardial ischaemia in an unselected population. Methods : We enrolled a total of 51 consecutive patients; referred for exercise stress 99mTc-sestamibi SPECT MPI (single-photon emission computed tomography myocardial perfusion imaging) to diagnose inducible myocardial ischaemia. NT-proBNP was determined at rest and 30 minutes after cessation of exercise. Results : Of the 51 patients; 28 had normal perfusion scans; seven had scans with fixed perfusion defects (previous myocardial infarction with no inducible ischaemia) and 16 had reversible perfusion defects (inducible ischaemia). There was no correlation between ischaemia and resting NT-proBNP; post-stress NT-proBNP or the change in NT-proBNP (delta-NT-proBNP). Conclusion : In an unselected population the change in NT-proBNP cannot be used to diagnose effort-induced myocardial ischaemia

4.
Clin Chim Acta ; 330(1-2): 111-9, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12636929

RESUMO

BACKGROUND: Numerous variations of the methionine load test are frequently used as dynamic function tests to assess homocysteine metabolism. Lack of standardization impedes inter-laboratory comparisons. Criteria based on biological variation are suggested to standardize the methionine load test. METHODS: Weekly methionine load tests (n=5) with blood sampling at 0, 4, 6 and 8 h were performed on 15 young men. For both basal and post-methionine load homocysteine measurements, total variance (sigma(S)(2)), within-subject variance (sigma(I)(2)), between-subject variance (sigma(G)(2)) and analytical variance (sigma(A)(2)) were calculated from an appropriate analysis of variance (ANOVA). RESULTS: Plasma homocysteine concentrations measured 6 h after methionine loading had analytical, within-subject and between-subject coefficients of variation of 5.2%, 17.5% and 9.7%, respectively. Measurements at 4 h had a higher within-subject coefficient of variation. Adjustment of post-methionine load homocysteine concentrations for basal levels resulted in considerable increases of all the measures of variation. CONCLUSIONS: Adjustment of post-methionine load plasma homocysteine concentrations for basal levels does not improve the interpretation of changes in serial results due to the higher analytical and biological variance of adjusted concentrations. It is suggested that the methionine load test is standardized to a single, unadjusted homocysteine measurement at 6 h.


Assuntos
Homocisteína/sangue , Metionina/farmacocinética , Adulto , Técnicas de Laboratório Clínico/normas , Jejum/sangue , Humanos , Laboratórios/normas , Masculino , Metionina/administração & dosagem , Valores de Referência , Estatística como Assunto/métodos , Fatores de Tempo
5.
S Afr Med J ; 92(6): 464-7, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12146133

RESUMO

OBJECTIVE: The frequencies of mutations 677C-->T and 1298A-->C in the methylenetetrahydrofolate reductase (MTHFR) gene, previously shown to be associated with decreased enzyme activity that may lead to hyperhomocysteinaemia and consequently increased risk of cardiovascular disease (CVD), were determined in the South African population. METHODS: HinfI (677C-->T) and MboII (1298A-->C) restriction enzyme analyses were performed on amplified DNA samples of 76 white, 73 coloured and 60 black subjects. RESULTS: The mutant alleles of mutations 677C-->T and 1298A-->C were more common in the white (allele frequencies 0.36 and 0.37, respectively) than in the black population (0.04 and 0.09), while intermediate frequencies were detected in the coloured population (0.18 and 0.30). Homozygosity for mutation 677C-->T was not detected in the black cohort, while this genotype was detected in 1 coloured (1.4%) and 8 white (10.5%) subjects. In the black population, 5% of the 60 subjects analysed were homozygous for mutation 1298A-->C, compared with approximately 12% in both the white and coloured populations. CONCLUSIONS: Since hyperhomocysteinaemia is a risk factor for premature CVD, the heterogeneous distribution of the 677C-->T and 1298A-->C mutations across ethnic groups may partly explain ethnic differences in heart disease risk through decreased enzyme activity and hence increased homocysteine levels.


Assuntos
Doenças Cardiovasculares/genética , Predisposição Genética para Doença/epidemiologia , Homocisteína/sangue , Homocisteína/genética , Mutação , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Doenças Cardiovasculares/etiologia , Predisposição Genética para Doença/genética , Genética Populacional , Homocisteína/efeitos adversos , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2) , África do Sul
7.
Artigo em Inglês | MEDLINE | ID: mdl-12076687

RESUMO

A validated gas chromatography-mass spectrometric method for the analysis of the metabolites of benzene and its alkylated analogues in urine is reported. A number of metabolites, as required by authorities for biomonitoring of industrial exposure to aromatic vapour, were analysed simultaneously with preservation of quantitative information concerning positional isomers. The use of this method replaces a combination of analytical methods required for the analysis of all these metabolites. Urine samples were subjected to acidic deconjugation followed by a derivatization step. Phenol, ortho-, meta-, para-cresol, mandelic acid, and ortho-, meta-, para-methylhippuric acid were analysed as their corresponding ethoxycarbonyl derivatives, with single ion monitoring. The mass-to-charge ratios (m/z) of the ions used for quantitation by single ion monitoring of the metabolites were: phenol, 94 m/z; cresols, 108 m/z; mandelic acid, 206 m/z; hippuric acid, 105 m/z; methylhippuric acids, 119 m/z. The mass-to-charge ratios for the internal standards were: [(2)H(6)]phenol, 99 m/z; p-chlorophenol, 128 m/z and 3-chloro-4-hydroxyphenyl acetic acid, 214 m/z. The limits of detection for phenol and the cresols were below 0.4 micromol/l and below 0.05 micromol/l for mandelic acid and the hippuric acids. Within-run precision for mandelic acid was 6.2%, for hippuric acid was 7.32% and was below 5% for the rest of the analytes.


Assuntos
Derivados de Benzeno/urina , Biomarcadores/urina , Cromatografia Gasosa-Espectrometria de Massas/métodos , Alquilação , Calibragem , Humanos , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
8.
Ann Clin Biochem ; 39(Pt 1): 39-43, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11858217

RESUMO

BACKGROUND: Sweat conductivity, which is equivalent to sweat NaCl concentration, is used as a screening test to identify possible cystic fibrosis (CF) patients. No data exist on the biological variation of this variable and the influence it may have on the interpretation of sweat testing. The aim of this study was to determine the components of biological variation for sweat sodium chloride conductivity and to apply biological variation parameters in the interpretation of sweat conductivity. METHODS: Sweat conductivity was determined once a week for 5 consecutive weeks on 15 healthy volunteers, 20 healthy infants and 20 known CF patients. RESULTS: The analytical coefficient of variation (CV(A)) was 1.15% for the high-level control material, with a value of 123 mmol/L, and 1.32% for the normal-level control material with a value of 40 mmoL/L. The within-subject (CV) and between-subject (CV(G)) biological variations were 12.0% and 30.0%, respectively, for healthy controls; 18% and 20% for healthy infants; and 7.3% and 6.5% for CF patients, respectively. Using the CV(A), CV(G) and CV(I), the 95% reference ranges were determined for the above-mentioned three groups. The calculated 95% ranges for the healthy babies and CF patients were 18-60 mmoL/L and 96-144 mmoL/L. CONCLUSIONS: Our data support a decision level of > 60 mmoL/L for confirmatory CF testing. A lower decision level will result in an unacceptable high rate of unnecessary confirmation testing.


Assuntos
Fibrose Cística/metabolismo , Cloreto de Sódio/metabolismo , Suor/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Fibrose Cística/diagnóstico , Condutividade Elétrica , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
9.
J Chromatogr B Biomed Sci Appl ; 762(2): 127-36, 2001 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-11678372

RESUMO

A validated gas chromatographic-mass spectrometric method for quantitation of phenylalanine and tyrosine in serum is described. Quantitation of phenylalanine and tyrosine with a non-labelled non-endogenous internal standard, L-2-chlorophenylalanine, compared favourably with isotope dilution mass spectrometric quantitation. The 95% reference ranges for phenylalanine. tyrosine and the phenylalanine-tyrosine molar ratio in neonate cord blood serum were determined by isotope dilution mass spectrometry and were found to be 77.1-144.7, 33.3-109.3 micromol/l and 1.1-3.0, respectively.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Fenilalanina/sangue , Tirosina/sangue , Sangue Fetal/química , Humanos , Recém-Nascido , Padrões de Referência , Valores de Referência
10.
Clin Chim Acta ; 303(1-2): 139-45, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11163034

RESUMO

BACKGROUND: Because of the lack of a problem-free, reliable method for determination of erythrocyte acetylcholinesterase (AChE), we developed a simple kinetic method, which we found to be both reliable and suitable for automation in the routine clinical laboratory. METHODS: Acetylthiocholine, used as substrate, is hydrolysed by acetylcholinesterase to yield acetate and thiocholine. Thiocholine reacts with dichlorophenolindophenol, a blue coloured compound, which is reduced to a colourless product, producing a linear decrease in absorption at 606 nm. If required, this assay can also be run at 600 nm with equally acceptable results. RESULTS: The method was automated on the Synchron LX20 multianalyser (Beckman Instruments) and blood samples of 80 patients with clinically symptomatic organophosphate poisoning and 153 normal controls were evaluated. Acetylcholinesterase values were in the range of 0-14 UgHb(-1) in cases of organophosphate poisoning, in contrast with normal controls, who had AChE values of 24.4--37.9 UgHb(-1). No overlap was found between AChE values of controls and poisoned cases. Intra- and inter-assay coefficients of variation were 1.68 and 3.71%, respectively. CONCLUSION: The method we propose for measurement of AChE was found to be simple, reliable and easily automatable in the routine clinical laboratory.


Assuntos
Acetilcolinesterase/sangue , Eritrócitos/enzimologia , Intoxicação por Organofosfatos , 2,6-Dicloroindofenol/metabolismo , Automação , Humanos , Cinética , Compostos Organofosforados/sangue , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
Clin Chem ; 46(8 Pt 1): 1085-90, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10926887

RESUMO

BACKGROUND: Screening for diabetes and hypercholesterolemia is widely advocated, and extra-laboratory testing could play a major role in cost-effective population screening. We wished to assess the analytical quality and interchangeability of capillary blood cholesterol and glucose assays as performed on near-patient devices in pharmacies in Pretoria, South Africa. METHODS: Accuracy of near-patient and laboratory analyzers was assessed by analyses of human-serum-based reference material. To assess interchangeability in routine use, six volunteers visited each of 12 randomly selected pharmacies consecutively during a 3-week period to have their fasting blood glucose and cholesterol concentrations determined. For comparison purposes, a similar procedure was followed to evaluate the eight clinical chemistry laboratories servicing Pretoria and surroundings. RESULTS: The analytical performances in our laboratory of a single point-of-care instrument and of a laboratory analyzer compared well. Nevertheless, between-pharmacy analytical variation was larger than between-laboratory variation (11% vs 6.1% for cholesterol; 10% vs 7.6% for glucose). For glucose measurements, near-patient testing in pharmacies demonstrated a bias of -48.1% to 16.2%, whereas bias for laboratory measurements was -1.0% to 7.4%. Cholesterol assays showed a bias of -5.6% to 16.6% in pharmacies compared with -10.6% to 3.7% in laboratories. The percentage of closeness to the homeostatic set point for a single glucose and cholesterol determination done in any pharmacy was 24.6% and 23.6%, respectively. The corresponding values for laboratories were 16.9% and 15.6%, respectively. CONCLUSIONS: Although modern point-of-care instruments allow high-quality blood analyses under ideal conditions, performance goals often are not achieved in practice as indicated by a higher uncertainty of cholesterol and glucose blood results when determined in pharmacies. Nonuniformity of calibration procedures, deficiencies in training, a lack of internal quality control, and the absence of an external quality assessment program may all contribute to the current state of affairs.


Assuntos
Glicemia/análise , Colesterol/sangue , Sistemas Automatizados de Assistência Junto ao Leito , Colesterol/normas , Glucose/normas , Humanos , Controle de Qualidade , Kit de Reagentes para Diagnóstico , Padrões de Referência
12.
Metabolism ; 49(8): 1092-6, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10954032

RESUMO

The cosupplementation of magnesium with calcium has been suggested to be beneficial in the prevention of osteoporosis. We investigated the effect of magnesium supplementation on parameters of bone resorption and fractional 45Ca absorption. Twenty apparently healthy women with a mean age of 39.2 +/- 9.2 years and an erythrocyte magnesium concentration less than 1.97 mmol/L were recruited into a controlled magnesium supplementation trial. During weeks 1 to 4, they received a daily control preparation, potassium/sodium citrate malate (PSCM). During weeks 5 to 8, the subjects received magnesium citrate malate (MCM) equivalent to 250 mg magnesium per day. During the fourth and eighth weeks, blood was collected for measurement of the serum intact parathyroid hormone (PTH) concentration and serum and erythrocyte magnesium concentration. Urine was collected for measurement of calcium, magnesium, creatinine, and deoxypyridinoline excretion. On the final day of each treatment period, 5 microCi45CaCl2 was administered orally, and the isotope was traced in the blood and urine over 7 hours. Urinary calcium, 45Ca, and deoxypyridinoline excretion, as well as serum intact PTH levels, showed no statistically significant changes as a result of magnesium supplementation. However, urinary magnesium excretion increased by 31.1% (P < .005) while fractional 45Ca absorption decreased by 23.5% (P < .001) as a result of magnesium supplementation. It is concluded that magnesium supplementation does not result in changes in bone resorption, while the fractional intestinal absorption of 45Ca appears to decrease.


Assuntos
Cloreto de Cálcio/farmacocinética , Radioisótopos de Cálcio , Suplementos Nutricionais , Eritrócitos/metabolismo , Absorção Intestinal/efeitos dos fármacos , Magnésio/administração & dosagem , Magnésio/sangue , Adulto , Aminoácidos/urina , Reabsorção Óssea/dietoterapia , Reabsorção Óssea/metabolismo , Cálcio/metabolismo , Cálcio/urina , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Magnésio/efeitos adversos , Hormônio Paratireóideo/sangue
13.
J Med Genet ; 37(7): 514-9, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10882754

RESUMO

In South Africa, the high prevalence of familial hypercholesterolaemia (FH) among Afrikaners, Jews, and Indians as a result of founder genes is in striking contrast to its reported virtual absence in the black population in general. In this study, the molecular basis of primary hypercholesterolaemia was studied in 16 Africans diagnosed with FH. DNA analysis using three screening methods resulted in the identification of seven different mutations in the coding region of the low density lipoprotein (LDLR) gene in 10 of the patients analysed. These included a 6 bp deletion (GCGATG) accounting for 28% of defective alleles, and six point mutations (D151H, R232W, R385Q, E387K, P678L, and R793Q) detected in single families. The Sotho patient with missense mutation R232W was also heterozygous for a de novo splicing defect 313+1G-->A. Several silent mutations/polymorphisms were detected in the LDLR and apolipoprotein B genes, including a base change (g-->t) at nucleotide position -175 in the FP2 LDLR regulatory element. This promoter variant was detected at a significantly higher (p<0.05) frequency in FH patients compared to controls and occurred in cis with mutation E387K in one family. Analysis of four intragenic LDLR gene polymorphisms showed that the same chromosomal background was identified at this locus in the four FH patients with the 6 bp deletion. Detection of the 6 bp deletion in Xhosa, Pedi, and Tswana FH patients suggests that it is an ancient mutation predating tribal separation approximately 3000 years ago.


Assuntos
Hiperlipoproteinemia Tipo II/genética , Receptores de LDL/genética , Adolescente , Adulto , Apolipoproteínas B/genética , População Negra/genética , Criança , Pré-Escolar , Análise Mutacional de DNA , Éxons , Feminino , Análise Heteroduplex , Humanos , Hiperlipoproteinemia Tipo II/epidemiologia , Íntrons , Masculino , Pessoa de Meia-Idade , Linhagem , Mutação Puntual , Polimorfismo Genético , Polimorfismo Conformacional de Fita Simples , Prevalência , Regiões Promotoras Genéticas , Deleção de Sequência , África do Sul/epidemiologia
14.
Eur J Clin Nutr ; 54(5): 373-9, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10822283

RESUMO

OBJECTIVE: To examine the effects of the inclusion of extruded dry beans in the diet on serum lipoprotein, plasma fibrinogen, plasma viscosity and plasminogen activator inhibitor 1 (PAI-1) levels. SUBJECTS AND STUDY DESIGN: Twenty-two free living hyperlipidaemic men participated in this randomised, controlled, cross-over study. The subjects were randomly assigned to one of two groups. After a run-in period of four weeks, during which subjects followed their normal diet with the exclusion of dry beans, group A had to include 110 g/day of extruded dry beans in the form of baked products for four weeks while group B continued with the run-in diet. A washout period of four weeks followed after which the experimental intervention was crossed-over. Anthropometric measurements, serum lipoproteins and haemostatic variables were measured with standard methods and dietary intakes were estimated with five-day dietary records at the beginning and end of each experimental period. RESULTS: Compliance was determined as 83.5% with a mean intake of 91. 9 g/day extruded dry beans. Extruded dry beans did not have significant effects on total serum cholesterol, low density lipoprotein cholesterol, triglycerides, apolipoprotein A or B, plasma fibrinogen and plasma viscosity concentrations. High density lipoprotein cholesterol concentrations decreased in both the dry bean and control periods. Lipoprotein (a) concentrations increased with intake of extruded dry beans, but this increase was probably not due to an independent effect of extruded dry beans. Plasminogen activator inhibitor 1 levels were significantly lower after the intake of extruded dry beans compared to the control period. CONCLUSIONS: The inclusion of 91.9 g extruded dry beans per day in the diet had no effects on serum lipoproteins, plasma fibrinogen and viscosity levels but decreased PAI-1 levels. SPONSORSHIP: Dry Bean Producers Organisation (South Africa) and the Potchefstroom University for Christian Higher Education, Potchefstroom, South Africa.


Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Dieta , Fabaceae , Hiperlipidemias/dietoterapia , Lipoproteínas/sangue , Plantas Medicinais , Apolipoproteínas A/análise , Apolipoproteínas B/sangue , Viscosidade Sanguínea , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Cross-Over , Fibrinogênio/análise , Humanos , Hiperlipidemias/sangue , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Triglicerídeos/sangue
15.
Clin Chem ; 45(5): 670-5, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10222354

RESUMO

BACKGROUND: Various methods are available to measure plasma total homocyst(e)ine (tHcy) concentrations, but whether plasma tHcy assays may be used interchangeably is not known. METHODS: Results from three different methods [HPLC with fluorescence detection, enzyme immunoassay (EIA), and fluorescence polarization immunoassay (FPIA)] to determine fasting (n = 163) and post-methionine load (n = 80) plasma tHcy concentrations were compared with those obtained by gas chromatography-mass spectrometry (GC-MS). Difference plots on non-transformed and log-transformed data were used to assess the agreement between HPLC and GC-MS, EIA and GC-MS, and FPIA and GC-MS. RESULTS: The closest agreement between methods was observed between GC-MS and FPIA for fasting tHcy concentrations, with 95% of the FPIA values between 19% above and 24% below the corresponding GC-MS results. Post-methionine load tHcy concentrations measured by EIA showed the least agreement with GC-MS, with 95% of values measured by EIA ranging between 52% above and 16% below the GC-MS values. With respect to GC-MS, the above-mentioned methods showed a negative bias for fasting tHcy concentrations, but a positive bias for both immunoassays for post-methionine load tHcy concentrations. CONCLUSIONS: The agreement among methods is insufficient to allow them to be used interchangeably. The intermethod differences emphasize the need for standardization of plasma tHcy assays.


Assuntos
Homocisteína/sangue , Imunoensaio de Fluorescência por Polarização , Corantes Fluorescentes , Fluorbenzenos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Técnicas Imunoenzimáticas , Kit de Reagentes para Diagnóstico
16.
Thromb Res ; 93(6): 253-64, 1999 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-10093966

RESUMO

It is suspected that not only fibrinogen concentration but also the quality of fibrin networks may contribute to cardiovascular risk. Evidence is accumulating that a "prudent" diet may protect against diseases associated with raised clotting factors. The effect of diet on fibrinogen is, however, still controversial. In a previous study performed in our laboratory, it was shown that dietary pectin influences fibrin network architecture in hypercholesterolaemic men without causing any changes in fibrinogen concentration. To elucidate the possible mechanisms, it was necessary to study the possibility that pectin may itself have indirect effects on fibrin network architecture. Pectin is fermented in the gastrointestinal tract to acetate, propionate, and butyrate. In humans, only acetate reaches the circulation beyond the liver. This investigation primarily examined the possibility that pectin may, through acetate, influence fibrin network architecture in vivo. The effects of pectin and acetate supplementation in hypercholesterolaemic subjects were compared. Furthermore, this study also aimed at describing the possible in vitro effects of acetate on fibrin network architecture. Two groups of 10 male hyperlipidaemic volunteers each received a pectin (15 g/day) or acetate (6.8 g/day) supplement for 4 weeks. Acetate supplementation did not cause a significant change in plasma fibrinogen levels. As in the pectin group, significant differences were found in the characteristics of fibrin networks developed in plasma after 4 weeks of acetate supplementation. Fibrin networks were more permeable (from 213+/-76 to 307+/-81 x 10(11) cm2), had lower tensile strength (from 23+/-3 to 32+/-9% compaction), and were more lyseable (from 252+/-11 to 130+/-15 minutes). These results strongly suggest that the effect of pectin on network architecture could partially be mediated by acetate. Progressive amounts of acetate were used in vitro to investigate the possibility that acetate may be directly responsible for changes that occurred in fibrin network architecture in the plasma medium. Results indicated that acetate influenced fibrin network architecture directly. From the results, it seems highly possible that acetate may be responsible in part for the beneficial effects of pectin supplementation in vivo. It is evident that pectin or acetate supplementation can be useful during the treatment or prevention of some clinical manifestations, especially those associated with raised total cholesterol and possibly also plasma fibrinogen.


Assuntos
Antidiarreicos/administração & dosagem , Fibrina/metabolismo , Fibrinogênio/metabolismo , Hipercolesterolemia/sangue , Pectinas/administração & dosagem , Adulto , Dieta , Suplementos Nutricionais , Fibrina/química , Produtos de Degradação da Fibrina e do Fibrinogênio/efeitos dos fármacos , Fibrinogênio/química , Humanos , Masculino , Pessoa de Meia-Idade
17.
Metabolism ; 48(2): 269-74, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10024094

RESUMO

The birth incidence of neural tube defects (NTDs) in South Africa is threefold to sixfold higher in rural compared with urban blacks. We investigated whether folate deficiency and aberrant homocysteine metabolism could explain the high NTD incidence in rural black populations. Plasma folate and total homocyst(e)ine (tHcy) concentrations were determined in apparently healthy rural black women (n = 107), rural black women with a history of pregnancy complicated by NTDs (n = 54), and urban blacks (n = 101). Methionine load tests were performed on the 54 women with a history of NTD-affected pregnancy and 54 controls matched for age and body mass. The presence of the 677C --> T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene was investigated in both groups by a polymerase chain reaction (PCR) of genomic DNA and HinfI digestion of the PCR product. Apparently healthy urban black women (n = 101) had a lower (P < .001) plasma folate concentration compared with rural black women (n = 107). Women with a history of NTD-affected pregnancy did not differ significantly from controls with respect to plasma folate, fasting homocyst(e)ine, methionine, and the post-methionine load increase in plasma homocyst(e)ine. More than 50% of both of the latter groups had a post-methionine load increase in plasma tHcy less than the fifth percentile as observed in a healthy white control group. No homozygotes for the 677C --> T mutation in the MTHFR gene were found in black mothers with NTD-affected offspring or controls. It is concluded that black urbanization is characterized by a diminished folate status that is paradoxically associated with a lower NTD birth incidence. Homozygosity for the 677C --> T mutation in the gene coding for MTHFR does not constitute a genetic risk factor for NTDs in blacks. No aberrant homocysteine metabolism could be demonstrated in black women with NTD-affected pregnancies.


Assuntos
Ácido Fólico/sangue , Homocisteína/metabolismo , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Defeitos do Tubo Neural/genética , Complicações na Gravidez/enzimologia , Adulto , População Negra , DNA/análise , DNA/genética , Feminino , Genótipo , Humanos , Metionina , Defeitos do Tubo Neural/enzimologia , Defeitos do Tubo Neural/epidemiologia , Estado Nutricional , Gravidez , Complicações na Gravidez/epidemiologia , População Rural , África do Sul/epidemiologia
18.
Atherosclerosis ; 140(2): 349-56, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9862278

RESUMO

Elevated circulating total homocyst(e)ine concentrations are associated with a higher prevalence of ischaemic heart disease (IHD). We utilized data from the Caerphilly Prospective Cohort Study to assess the predictive power of the serum total homocyst(e)ine concentration for future IHD. Serum total homocyst(e)ine concentrations were measured in 2290 men in the Caerphilly cohort, a representative population sample of men aged 50-64 years. During a 5-year follow-up period, 56 men suffered fatal IHD, 77 had a non-fatal myocardial infarction, while 21 were found to have ECG evidence of myocardial infarction (MI) when examined at follow-up. The mean serum total homocyst(e)ine concentration in the total of 154 men who experienced an incident IHD event was 12.4 micromol/l, whereas the 2136 men who experienced no such event had a mean level of 11.7 micromol/l. The difference between these means, examined by logistic regression and standardising for the effects of differences in age, social class, smoking, BMI, diabetes, HDL-cholesterol and prevalent IHD is 0.47 micromol/l (95% CI = -0.13 to 1.11 micromol/l). The mean difference for the 56 men who died, and whose death was attributed to IHD, is 0.81 micromol/l (95% CI= -0.17 to 1.88 micromol/l) after correction for confounding factors. Vitamin nutritional status and alcohol intake were significant negative determinants of serum total homocyst(e)ine concentrations; the effect of alcohol is explained by the folic acid content of beer, which is the preferred alcoholic beverage in Caerphilly. It is concluded that the serum total homocyst(e)ine concentration is weakly predictive of IHD events, though in the present data adjustments for other factors attenuated the relationship and it became not statistically significant (P > 0.05).


Assuntos
Homocisteína/sangue , Isquemia Miocárdica/epidemiologia , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Dieta , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/prevenção & controle , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , População Urbana , Vitaminas/uso terapêutico , País de Gales/epidemiologia
19.
Eur J Clin Nutr ; 52(6): 419-24, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9683394

RESUMO

OBJECTIVE: To examine the effects of lecithin on serum lipoprotein, plasma fibrinogen and macro molecular protein complex (MPC) levels. SUBJECTS AND STUDY DESIGN: Twenty free living hyperlipidaemic men participated in this double-blind study which controlled for possible indirect effects. The subjects were randomly assigned to one of three treatments: frozen yoghurt or frozen yoghurt with 20 g soya bean lecithin or frozen yoghurt with 17 g sunflower oil. Sunflower oil was used to control for the increased energy and linoleic acid intake from lecithin. Yoghurt served as the 'vehicle' for the lecithin and sunflower oil and yoghurt alone was given to one group to control for possible effects due to the yoghurt 'vehicle', as well as other environmental influences. Variables were measured with standard methods twice at baseline and after 2 and 4 weeks of treatment. RESULTS: Plasma linoleic acid levels increased significantly with lecithin and sunflower oil treatments indicating that compliance to the treatments were obtained. Lecithin treatment did not have significant effects on serum total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein A, apolipoprotein B or lipoprotein (a) levels. Plasma fibrinogen and MPC levels were also not affected by lecithin therapy. Sunflower oil treatment resulted in significant increased body weight, serum TC and decreased MPC levels. CONCLUSION: Lecithin treatment had no independent effects on serum lipoprotein, plasma fibrinogen or MPC levels in hyperlipidaemic men.


Assuntos
Proteínas Sanguíneas/metabolismo , Fibrinogênio/metabolismo , Hiperlipidemias/sangue , Lipoproteínas/sangue , Fosfatidilcolinas/farmacologia , Adulto , Apolipoproteínas B/sangue , Colesterol/sangue , Método Duplo-Cego , Humanos , Lipoproteína(a)/sangue , Substâncias Macromoleculares , Masculino , Pessoa de Meia-Idade , Ácido Palmítico/sangue , Fosfatidilcolinas/administração & dosagem , Óleos de Plantas/administração & dosagem , Glycine max , Óleo de Girassol , Iogurte
20.
Clin Chim Acta ; 278(1): 55-60, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9877124

RESUMO

Decreased antioxidant-vitamin nutritional status may increase lipid peroxidation and susceptibility of low-density lipoprotein (LDL) to oxidative modification. The aim of this study was to evaluate the vitamin nutritional status of coronary artery disease (CAD) patients and to assess the risk of CAD related to each individual antioxidant vitamin. The study was performed as a case-control study with 41 patients with angiographically demonstrated CAD and 41 apparently healthy age- and smoking status-matched controls. Plasma vitamin E, C and A concentrations were significantly decreased in CAD patients compared with controls (p < 0.001) after correcting for significant covariates. Per quartile decrease in vitamin A and E concentrations was associated with increased risk of CAD, even after adjusting for CAD risk factors, while per quartile decrease in vitamin C concentrations was not associated with significant CAD risk after adjusting for CAD risk factors. Decreased vitamin A and E concentrations are independently associated with increased risk of CAD independent from other CAD risk factors in white male South Africans and dietary intervention strategies are advocated.


Assuntos
Antioxidantes/uso terapêutico , Doença das Coronárias/prevenção & controle , Vitaminas/uso terapêutico , Adulto , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença das Coronárias/epidemiologia , Doença das Coronárias/metabolismo , Humanos , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Fumar , África do Sul/epidemiologia
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