RESUMEN
Homocysteine, an atherogenic amino acid, is either remethylated to methionine or metabolized to cysteine by the transsulfuration pathway. The biochemical conversion of homocysteine to cysteine is dependent upon two consecutive, vitamin B-6-dependent reactions. To study the effect of a selective vitamin B-6 deficiency on transsulfuration, we performed oral methionine load tests on 22 vitamin B-6-deficient asthma patients treated with theophylline (a vitamin B-6 antagonist) and 24 age- and sex-matched controls with a normal vitamin B-6 status. Both groups had normal circulating vitamin B-12 and folate concentrations. Methionine loading resulted in significantly higher increases in circulating total homocyst(e)ine (P < 0.01) and cystathionine (P < 0.05) concentrations in vitamin B-6-deficient patients compared with controls. 6 wk of vitamin B-6 supplementation (20 mg/d) significantly (P < 0.05) reduced post-methionine load increases in circulating total homocyst(e)ine concentrations in deficient subjects, but had no significant effect on the increase in total homocyst(e)ine concentrations in controls. The increases in post-methionine load circulating cystathionine concentrations were significantly (P < 0.01) reduced in both groups after vitamin supplementation. It is concluded that a vitamin B-6 deficiency may contribute to impaired transsulfuration and an abnormal methionine load test, which is associated with premature vascular disease.
Asunto(s)
Homocisteína/sangre , Metionina/metabolismo , Piridoxina/farmacología , Deficiencia de Vitamina B 6/metabolismo , Administración Oral , Adulto , Asma/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Cistationina/sangre , Femenino , Humanos , Masculino , Metionina/administración & dosificación , Persona de Mediana Edad , Teofilina/uso terapéutico , Deficiencia de Vitamina B 6/inducido químicamenteRESUMEN
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.
Asunto(s)
Hiperlipoproteinemia Tipo II/genética , Receptores de LDL/genética , Adolescente , Adulto , Apolipoproteínas B/genética , Población Negra/genética , Niño , Preescolar , Análisis Mutacional de ADN , Exones , Femenino , Análisis Heterodúplex , Humanos , Hiperlipoproteinemia Tipo II/epidemiología , Intrones , Masculino , Persona de Mediana Edad , Linaje , Mutación Puntual , Polimorfismo Genético , Polimorfismo Conformacional Retorcido-Simple , Prevalencia , Regiones Promotoras Genéticas , Eliminación de Secuencia , Sudáfrica/epidemiologíaRESUMEN
We measured the vitamin B-6, vitamin B-12, and folic acid nutritional status in a group of apparently healthy men (n = 44) with moderate hyperhomocysteinemia (plasma homocysteine concentration > 16.3 mumol/L). Compared with control subjects (n = 274) with normal plasma homocysteine (< or = 16.3 mumol/L) concentrations, significantly lower plasma concentrations of pyridoxal-5'-phosphate (P < 0.001), cobalamin (P < 0.001), and folic acid (P = 0.004) were demonstrated in hyperhomocysteinemic men. The prevalence of suboptimal vitamin B-6, B-12, and folate status in men with hyperhomocysteinemia was 25.0%, 56.8%, and 59.1%, respectively. In a placebo-controlled follow-up study, a daily vitamin supplement (10 mg pyridoxal, 1.0 mg folic acid, 0.4 mg cyanocobalamin) normalized elevated plasma homocysteine concentrations within 6 wk. Because hyperhomocysteinemia is implicated as a risk factor for premature occlusive vascular disease, appropriate vitamin therapy may be both efficient and cost-effective to control elevated plasma homocysteine concentrations.
Asunto(s)
Ácido Fólico/sangre , Homocisteína/sangre , Piridoxina/sangre , Vitamina B 12/sangre , Adulto , Anciano , Enfermedades Cardiovasculares/prevención & control , Cistationina betasintasa/deficiencia , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Ácido Fólico/administración & dosificación , Ácido Fólico/uso terapéutico , Deficiencia de Ácido Fólico/complicaciones , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Piridoxina/administración & dosificación , Piridoxina/uso terapéutico , Vitamina B 12/administración & dosificación , Vitamina B 12/uso terapéutico , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 6/complicacionesRESUMEN
We investigated the vitamin B-6 status in smokers, nonsmokers, and exsmokers by measuring both B-6 aldehyde vitamers, pyridoxal-5'-phosphate (PLP) and pyridoxal (PL), in the plasma as well as in the erythrocyte compartment. Two hundred eighty-six healthy, sedentary male workers from a middle-income group were investigated. There were 159 smokers, 59 exsmokers, and 68 nonsmokers. Plasma PLP and PL concentrations were significantly lower in smokers than in the nonsmokers and exsmokers whereas erythrocyte PLP and PL did not differ significantly between groups. Because PLP mainly functions as an intracellular coenzyme, the clinical significance of a depressed plasma PLP concentration alone is uncertain. It is concluded that circulating plasma PLP is labile and not necessarily indicative of intracellular PLP concentrations. The measurement of erythrocyte PLP and/or PL may be more informative about vitamin B-6 status than is plasma PLP alone.
Asunto(s)
Estado Nutricional/fisiología , Piridoxina/sangre , Fumar/sangre , Adulto , Anciano , Eritrocitos/análisis , Humanos , Masculino , Persona de Mediana Edad , Plantas Tóxicas , Piridoxal/sangre , Fosfato de Piridoxal/sangre , NicotianaRESUMEN
L-Methionine (0.1 g/kg body wt) was administered to young white [n = 18; mean (+/- SD) age 20.0 +/- 1.0 y] and black [n = 12; mean (+/- SD) age 22.0 +/- 1.3 y] volunteers who had a similar lifestyle and who did not differ significantly from each other with respect to plasma folate or vitamin B-12 concentrations. Blacks, however, had significantly lower plasma pyridoxal-5'-phosphate concentrations compared with whites (P < 0.001). Fasting plasma homocysteine concentrations in blacks and whites were not significantly different. The mean (+/- SD) maximum increase in plasma homocysteine concentration measured after methionine loading was significantly lower (P < 0.01) in blacks (11.0 +/- 3.6 mumol/L) than in whites (18.0 +/- 6.2 mumol/L). Six weeks of vitamin supplementation (1.0 mg folic acid, 400 micrograms vitamin B-12, and 10 mg pyridoxine/d) reduced the mean (+/- SD) fasting plasma homocysteine concentration from 9.6 +/- 3.5 to 7.2 +/- 1.6 mumol/L in whites (P < 0.05) and from 8.4 +/- 2.4 to 5.6 +/- 1.4 mumol/L in blacks (P < 0.01). The mean (+/- SD) maximum increase in plasma homocysteine concentration after methionine loading declined from 18.0 +/- 6.2 to 11.1 +/- 2.3 mumol/L (P < 0.01) in whites, but vitamin supplementation did not have a significant effect on the methionine-load test in black volunteers. A significant race-by-time interaction shows that blacks metabolized homocysteine more effectively than did whites, which may partly explain their relative resistance against coronary heart disease despite a high prevalence of obesity, hypertension, and smoking.
Asunto(s)
Población Negra , Enfermedad Coronaria/etnología , Homocisteína/metabolismo , Metionina/metabolismo , Población Blanca , Adulto , Población Negra/genética , Enfermedad Coronaria/genética , Ácido Fólico/sangre , Homocisteína/sangre , Homocisteína/genética , Humanos , Masculino , Metionina/administración & dosificación , Metionina/sangre , Sudáfrica/epidemiología , Vitamina B 12/sangre , Vitaminas/administración & dosificación , Población Blanca/genéticaRESUMEN
The effect of different ratios of the prostaglandin precursors gamma-linolenic (GLA) and eicosapentaenoic (EPA) acids on bone status in growing rats measured as a function of free urinary pyridinium crosslinks and hydroxyproline levels was investigated. Male Sprague-Dawley rats were weaned onto an essential fatty acid deficient diet and from their fifth week, different groups of rats received a balanced, semisynthetic diet, supplemented with different ratios of GLA:EPA supplied as a mixture of evening primrose oil (EPO) and fish oil (FO). Controls were supplemented with linoleic (LA; sunflower oil) and alpha-linolenic (ALA; linseed oil) acids (3:1) or a commercially available rat chow. Animals were terminated at 84 days and femur length, ash weight, calcium content, free urinary pyridinium crosslinks (Pyd and Dpyd), total hydroxyproline (Hyp), and creatinine levels measured. Free urinary Pyd and Dpyd are good indicators of bone status and they correlated well with Hyp. Pyd and Dpyd excretion were significantly decreased in the higher GLA:EPA dietary groups and correlated well (r = 0.7) with Hyp levels. Concomitantly, bone calcium content increased significantly in the same dietary groups. These results suggest that diet supplementation with relatively high GLA:EPA ratios are more effective in inhibiting bone resorption than LA:ALA.
Asunto(s)
Calcio/metabolismo , Ácido Eicosapentaenoico/farmacología , Fémur/efectos de los fármacos , Hidroxiprolina/orina , Ácido gammalinolénico/farmacología , Aminoácidos/orina , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Resorción Ósea/tratamiento farmacológico , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Ácido Eicosapentaenoico/administración & dosificación , Ácido Eicosapentaenoico/uso terapéutico , Ácidos Grasos/metabolismo , Ácidos Grasos Esenciales/administración & dosificación , Fémur/fisiología , Aceites de Pescado/administración & dosificación , Ácidos Linoleicos , Lípidos/sangre , Masculino , Oenothera biennis , Tamaño de los Órganos/efectos de los fármacos , Aceites de Plantas , Ratas , Ratas Sprague-Dawley , Espectrometría de Fluorescencia , Ácido gammalinolénico/administración & dosificación , Ácido gammalinolénico/uso terapéuticoRESUMEN
The finding of low plasma pyridoxal-5'-phosphate levels in patients suffering from myocardial infarction has been construed as possible evidence for the pathogenetic role that vitamin B6 deficiency may play in causing premature ischaemic heart disease. However, the presence of normal plasma pyridoxal-5'-phosphate levels in patients with angiographic evidence of coronary artery narrowing but with no previous infarctions prompted the investigation of possible short-term alterations in plasma pyridoxal-5'-phosphate levels during the acute phase of myocardial infarction. In the follow-up of 30 patients with acute myocardial infarction, all of them showed a continuous decrease of approximately 45% in plasma pyridoxal-5'-phosphate levels during the acute phase. These levels subsequently returned back to normal before discharge from hospital. A large number of volunteers from an ethnic group known to have a very low incidence of ischaemic heart disease were found to have both significantly lower total cholesterol and plasma pyridoxal-5'-phosphate levels than a Caucasian group in the same geographic area which is known to have a high incidence of ischaemic heart disease. These findings therefore do not support the contention that vitamin B6 deficiency may be a risk index for ischaemic heart disease.
Asunto(s)
Enfermedad Coronaria/sangre , Fosfato de Piridoxal/sangre , Adulto , Negro o Afroamericano , Población Negra , Colesterol/sangre , HDL-Colesterol/sangre , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/etnología , Enfermedad Coronaria/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Riesgo , Sudáfrica , Deficiencia de Vitamina B 6/sangre , Deficiencia de Vitamina B 6/complicaciones , Deficiencia de Vitamina B 6/etnología , Población BlancaRESUMEN
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).
Asunto(s)
Homocisteína/sangre , Isquemia Miocárdica/epidemiología , Biomarcadores/sangre , Cromatografía Líquida de Alta Presión , Dieta , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/sangre , Isquemia Miocárdica/prevención & control , Prevalencia , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Población Urbana , Vitaminas/uso terapéutico , Gales/epidemiologíaRESUMEN
Dietary fat intake is often regarded as a major determinant of coronary heart disease (CHD) rate and it has been deemed unnecessary to invoke racial or other factors to explain the differences in CHD rates among different ethnic groups. Despite a high prevalence of CHD risk factors such as hypertension, obesity, and smoking, CHD remains a rarity in westernized black Africans. Cord blood total cholesterol (TC), low density lipoprotein cholesterol (LDLC) and apolipoprotein B (apo B) levels were measured and found to be respectively 12.1%, 18.3% and 22.4% lower in black neonates when compared to white neonates. These differences were again studied in a group of young black African males and a comparable group of age-matched whites who had been exposed to the same environment and western diet for at least 2 years. Although the body mass indices and serum albumin concentrations in the adult males were not significantly different, serum levels of TC, LDLC and apo B were 10.7%, 18.7% and 39.7% lower in the blacks, respectively. Furthermore, high density lipoprotein cholesterol (HDLC) and Apolipoprotein AI were 20.2% and 9.5% higher, homocysteine 45.6% lower and coagulation factor VII 26.6% lower in the adult black Africans. It is concluded that blacks are biochemically less responsive to an atherogenic diet than whites and these differences are already present at birth.
Asunto(s)
Población Negra , Enfermedad Coronaria/etnología , Población Blanca , Adulto , Constitución Corporal , Enfermedad Coronaria/sangre , Susceptibilidad a Enfermedades , Sangre Fetal/química , Humanos , Recién Nacido , Lípidos/sangre , Masculino , Factores de Riesgo , Albúmina Sérica/análisisRESUMEN
Based on a meta-analysis of published studies, it has been estimated that approximately 10% of coronary artery disease cases are attributable to hyperhomocyst(e)inemia. It has also been calculated that food fortification with folate might reduce the number of cases of coronary artery disease in the United States by 50,000 per year. However, the use of statistical concepts to estimate the expected benefits of this intervention strategy may be misleading.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Ácido Fólico/farmacología , Enfermedades Cardiovasculares/prevención & control , Dieta/normas , Ácido Fólico/administración & dosificación , Ácido Fólico/normas , Alimentos Fortificados , Humanos , Incidencia , Metaanálisis como Asunto , Estados Unidos/epidemiologíaRESUMEN
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.
Asunto(s)
Cloruro de Calcio/farmacocinética , Radioisótopos de Calcio , Suplementos Dietéticos , Eritrocitos/metabolismo , Absorción Intestinal/efectos de los fármacos , Magnesio/administración & dosificación , Magnesio/sangre , Adulto , Aminoácidos/orina , Resorción Ósea/dietoterapia , Resorción Ósea/metabolismo , Calcio/metabolismo , Calcio/orina , Eritrocitos/efectos de los fármacos , Femenino , Humanos , Magnesio/efectos adversos , Hormona Paratiroidea/sangreRESUMEN
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.
Asunto(s)
Ácido Fólico/sangre , Homocisteína/metabolismo , Metilenotetrahidrofolato Deshidrogenasa (NADP)/genética , Defectos del Tubo Neural/genética , Complicaciones del Embarazo/enzimología , Adulto , Población Negra , ADN/análisis , ADN/genética , Femenino , Genotipo , Humanos , Metionina , Defectos del Tubo Neural/enzimología , Defectos del Tubo Neural/epidemiología , Estado Nutricional , Embarazo , Complicaciones del Embarazo/epidemiología , Población Rural , Sudáfrica/epidemiologíaRESUMEN
Hyperhomocysteinemia is regarded as a risk factor for stroke but its pathogenetic role has not yet been established in Black patients. We studied 24 Black patients admitted with cerebral thrombosis, and compared them with age- and sex-matched apparently healthy controls from the same community. Total homocysteine (tHcy) (free homocysteine, protein-bound homocysteine, the disulfide homocystine and the mixed disulfide homocysteine-cysteine) concentration was 10.91 (4.95-23.05) mumol/l in the stroke patients and 8.73 (3.95-15.10) mumol/l in controls (p = 0.031). This difference could not be explained by differences in vitamin B12, vitamin B6 or folate status. A subgroup of nine stroke patients with hypercreatininaemia (> 90 mumol/l, 75% of control concentrations) had significantly higher plasma tHcy concentrations [median (range) 9.10 (5.40-15.10) mumol/l] compared with controls [8.65 (3.96-13.89) mumol/l] (p = 0.002). Plasma tHcy concentrations of stroke patients with normal serum creatinine concentrations were not significantly different to those of controls. Hyperhomocysteinemia in Black patients with stroke may be partially caused by renal insufficiency. Therefore, while hyperhomocysteinemia may increase the risk of stroke, it is unlikely to be a primary initiating factor.
Asunto(s)
Población Negra , Homocisteína/sangre , Embolia y Trombosis Intracraneal/sangre , Embolia y Trombosis Intracraneal/etnología , Estudios de Casos y Controles , Colesterol/sangre , Creatina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piridoxina/sangre , Vitamina B 12/sangreRESUMEN
Fibrinogen is an important risk factor for atherosclerosis, stroke and cardiovascular heart disease (CHD). This risk is increased when associated with a high serum cholesterol. Furthermore, it is also believed that not only fibrinogen concentration, but also the quality of fibrin networks may be an important risk factor for the development of CHD. CHD and stroke as a result of atherosclerosis, plus the related problems of hyperinsulinaemia, hyperlipidaemia and hypertension are strongly related to diet. The "western" diet, defined by low fibre and high fat, sucrose and animal protein intakes, appears to be a major factor leading to death. It has been established that the water-soluble dietary fibre, pectin, significantly decrease the concentration of serum cholesterol levels. Evidence is also accumulating that a diet rich in fibre may protect against diseases associated with raised clotting factors. This investigation studied the possible effects of pectin on fibrinogen levels and fibrin network architecture. Two groups of 10 male hyperlipidaemic volunteers each, received a pectin supplement (15 g/day) or placebo (15 g/day) for 4 weeks. Lipid and fibrin network structure variables were measured at baseline and the end of supplementation. Pectin supplementation caused significant decreases in total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A & B and lipoprotein (a). Significant changes in the characteristics of fibrin networks developed in the plasma of the pectin supplemented group indicated that networks were more permeable and had lower tensile strength. These network structures are believed to be less atherogenic. It is suspected that pectin modified network characteristics by a combination of its effects on metabolism and altered fibrin conversion. This confirms the therapeutic possibilities of dietary intervention. Furthermore, this study also showed that changes in plasma fibrinogen need not be present to induce alterations in fibrin network architecture.
Asunto(s)
Fibras de la Dieta/administración & dosificación , Fibrina/química , Fibrina/metabolismo , Hipercolesterolemia/sangre , Hipercolesterolemia/dietoterapia , Pectinas/administración & dosificación , Adulto , Colesterol/sangre , Enfermedad Coronaria/etiología , Enfermedad Coronaria/prevención & control , Método Doble Ciego , Fibrinógeno/metabolismo , Hemostasis , Humanos , Hipercolesterolemia/complicaciones , Lípidos/sangre , Masculino , Persona de Mediana Edad , Estructura Molecular , Factores de RiesgoRESUMEN
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.
Asunto(s)
Antidiarreicos/administración & dosificación , Fibrina/metabolismo , Fibrinógeno/metabolismo , Hipercolesterolemia/sangre , Pectinas/administración & dosificación , Adulto , Dieta , Suplementos Dietéticos , Fibrina/química , Productos de Degradación de Fibrina-Fibrinógeno/efectos de los fármacos , Fibrinógeno/química , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The stability of homocysteine in whole blood and plasma was investigated. Total homocysteine concentrations in whole blood increased rapidly to values in excess of 180% of the basal concentration if whole blood was left at ambient temperature. Sodium fluoride partially inhibited homocysteine accumulation, while refrigeration inhibited homocysteine accumulation for at least 4 h. Since intracellular concentrations of homocysteine were low, the results indicate continued metabolism of L-methionine to homocysteine after the blood sample had been obtained. In contrast to whole blood, homocysteine was stable in plasma, even at room temperature. Food consumption (normal breakfast) resulted in significantly lower plasma homocysteine concentrations, which returned to pre-prandial concentrations 8 h later. The results indicate that both blood sampling and food intake should be rigorously standardized in epidemiological studies to elucidate the possible role of elevated circulating homocysteine concentrations in premature vascular disease.
Asunto(s)
Ingestión de Alimentos/fisiología , Homocisteína/sangre , Manejo de Especímenes/métodos , Adulto , Ácido Edético , Femenino , Humanos , Masculino , RefrigeraciónRESUMEN
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.
Asunto(s)
Homocisteína/sangre , Metionina/farmacocinética , Adulto , Técnicas de Laboratorio Clínico/normas , Ayuno/sangre , Humanos , Laboratorios/normas , Masculino , Metionina/administración & dosificación , Valores de Referencia , Estadística como Asunto/métodos , Factores de TiempoRESUMEN
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.
Asunto(s)
Acetilcolinesterasa/sangre , Eritrocitos/enzimología , Intoxicación por Organofosfatos , 2,6-Dicloroindofenol/metabolismo , Automatización , Humanos , Cinética , Compuestos Organofosforados/sangre , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
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.
Asunto(s)
Antioxidantes/uso terapéutico , Enfermedad Coronaria/prevención & control , Vitaminas/uso terapéutico , Adulto , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/metabolismo , Humanos , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Fumar , Sudáfrica/epidemiologíaRESUMEN
The aim of this study was to monitor the antioxidant status of patients with hypercholesterolaemia during treatment with Simvastatin. Forty-seven patients, of whom 25 had confirmed familial hypercholesterolaemia (FH), were treated with 10 or 20 mg of Simvastatin per day for 14 weeks. As expected, total cholesterol and LDL cholesterol concentrations decreased considerably, while HDL cholesterol concentrations increased during drug treatment. In neither FH nor non-FH patients were any significant changes observed for retinol status, while plasma vitamin C concentrations were also not adversely affected by the drug therapy. In both patient groups Simvastatin therapy led to a significant decrease in plasma alpha-tocopherol (P < 0.05) concentrations, however, the alpha-tocopherol/total cholesterol ratio increased by 9.1 (P < 0.01) and 12.1% (P < 0.01) in FH and non-FH patients, respectively, during the 14-week treatment period. The coenzyme Q10/total cholesterol ratio did not change significantly in non-FH patients, but was significantly lower (P < 0.05) than the baseline ratio after 4 and 14 weeks of Simvastatin treatment in FH patients. The alpha-tocopherol/total cholesterol ratio of FH patients remained consistently and significantly lower (P < 0.01) compared with non-FH patients, indicating that LDL from the former group may be more vulnerable to free radical-mediated damage and lipid peroxidation. Our results suggest that the significant decline in circulating alpha-tocopherol and coenzyme Q10 concentrations was mainly a function of the decrease in serum total cholesterol concentrations.