Intervalo de referencia de homocisteína plasmática por inmunoanálisis de fluorescencia polarizada (IMx®) en niños / Plasma homocysteine reference interval by a fluorescence polarization immunoassay (Imx) in children

Elevadas concentraciones de homocisteína total en plasma son consideradas un factor de riesgo de enfermedad vascular aterotrombótica. Su determinación resulta de gran utilidad en el diagnóstico de la homocistinuria. El objetivo de este estudio es el establecimiento del intervalo de referencia por un procedimiento de inmunoanálisis de fluorescencia polarizada (IMx®, Abbott Laboratories) en una población de niños sanos. Se han seleccionado muestras de 178 niños (102 varones y 76 hembras) en edades comprendidas entre 3 meses y 15 años (x- ñ s = 7,45 ñ 4,30) divididos en tres grupos. El análisis de varianza demostró que existen diferencias significativas de la homocisteína plasmática en relación con la edad (p <0,001). No encontramos diferencias significativas entre sexos. Los niveles de homocisteína se asociaron positivamente con la creatinina (r = 0,55; p < 0,01).Los intervalos de referencia de la homocisteína plasmática para los tres grupos estudiados fueron: < 6 años = 2,17-7,11 µmol/L; 6-10 años=2,87-7,95 µmol/Ly 11-15 años=3,00-10,70 µmol/L. En conclusión: Se ha establecido el intervalo de referencia de la homocisteína plasmática en niños. Existe un aumento de la homocisteína con la edad, pero no existen diferencias significativas con respecto al sexo (AU)

[Subclinical carotid atherosclerosis in patients with coronary disease]. / Aterosclerosis subclínica de la arteria carótida en pacientes con enfermedad coronaria.

BACKGROUND: B-mode ultrasonography is a simple and valid method to evaluate subclinical atherosclerosis of the major superficial arteries. The aim of this study was toknow by this technique the prevalence of carotid atherosclerosisin patients with coronary disease and related factors. PATIENTS AND METHOD: In 232patients (205 men and 27 women; age: mean [standard deviation]59 [8] years) with coronary disease, intima-media thickness (IMT),presence and number of atheroma plaques in carotid arteries wereevaluated by B-mode ultrasonography. Controls were 50 healthy subjects whose age was not different from patients. Carotid atherosclerosis was considered when IMT was higher than mean plus two standarddeviations of control values, and/or existence of atheroma plaques. RESULTS: Carotid IMT wasincreased in patients compared to controls 0.82 [0.22] vs 0.62[0.12] mm; p < 0.001) and there were more patients with plaques(67 vs 20%; p < 0.001). Carotid atherosclerosis was found in170 patients and 11 controls (73 vs 22%; p < 0.001). By multivariate analysis, carotid atherosclerosis was associated with age (oddsratio: 1.05; 95% confidence interval [CI], 1.01-1.09) and smoking(odds ratio, 2.11; 95% CI: 1.04-4.26). The presence of more thanone plaque was associated with levels of low-density-lipoprotein(LDL)-cholesterol (odds ratio, 1.01; 95% CI, 1.00-1.02). CONCLUSIONS: In the patients with coronary disease, prevalence of subclinical carotid atherosclerosisis very high (73%), and it is associated with age and smoking. The advanced stage of atherosclerosis, evaluated by the existence of more than one plaque, is correlated with LDL-cholesterol levels.

[Influence of menopausal status in homocysteine plasma levels]. / Influencia de la menopausia en la concentración plasmática de homocisteína.

BACKGROUND: Some studies have found that postmenopausal women have increased plasma homocysteine levels while others do not. The aim of this study was to know if homocysteine levels are increased in Spanish postmenopausal women. PATIENTS AND METHODS: In 100 postmenopausal women (age: mean [SD] 56 [6] years) homocysteine, creatinine, folic acid, vitamin B12 and lipoproteins were determined. Controls were 50 premenopausal women (age: 29 [6] years), 50 men with similar age to postmenopausal women, and 50 men with similar age to premenopausal women. All the subjects of the study were healthy. RESULTS: Homocysteine concentrations were higher in postmenopausal compared with premenopausal women (8.6 [2.1]; 95% confidence interval [CI], 8.2-9.1 vs 7.7 [1.6]; 95% CI, 7.2-8.1 micromol/l; p < 0.05), but were not different between both men groups. Hyperhomocysteinemia was found in 9 postmenopausal but in any premenopausal women (9% vs 0%; p = 0.03). Low density lipoprotein cholesterol values were higher (155 [32]; 95% CI, 148-161 vs 111 [32]; 95% CI, 101-120 mg/dl; p < 0.05), and high density lipoprotein cholesterol lower (54 [12]; 95% CI, 52-57 vs 64 [18]; 95% CI, 59-69 mg/dl; p < 0.05) in postmenopausal than premenopausal women. In postmenopausal women homocysteine levels were negatively associated with folic acid and positively associated with creatinine levels, but there was not association with age, vitamin B12 serum levels and lipoproteins. CONCLUSION: In postmenopausal women increased homocysteine concentrations, together with hypercholesterolemia, could contribute to the raise of their cardiovascular risk.

Estudio de correlación de Homocisteína plasmática por cromatografía de intercambio iónico e inmunoanálisis de fluorescencia polarizada / Correlation sutdy of plasmatic homocysteine by ion-exchange chromatography and fluorescence

La determinación de Homocisteína plasmática tiene interés por ser un factor de riesgo independiente de padecer enfermedad cardiovascular. Los laboratorios clínicos deben ofrecer métodos para su determinación que sean rápidos y fiables, debido al importante papel que presentan los diferentes parámetros bioquímicos en el diagnóstico de la aterosclerosis. Nuestro laboratorio desarrolló un método de cromatografía de intercambio iónico utilizando un sistema de detección postcolumna de ninhidrina, el cual es lento y unido al aumento de la demanda de peticiones para la determinación de Homocisteína plasmática, nos llevó a evaluar un nuevo método de inmunoanálisis de fluorescencia polarizada completamente automatizado. Hemos evaluado y comparado ambos métodos. Los coeficientes de variación intra e interserie oscilaron entre 0,93 y 5,31 por ciento. La media de las recuperaciones obtenidas fue de 98,5 por ciento para ambos métodos. El límite de detección obtenido fue de 0,75 µmol/L y 0,79 µmol/L para el método cromatográfico y para el de inmunoanálisis de fluorescencia polarizada respectivamente. Encontramos una buena correlación entre el método de cromatografía de intercambio iónico y el de inmunoanálisis de fluorescencia polarizada (y = 0,81 + 1,65x; r = 0,98). En conclusión, el método de inmunoanálisis de fluorescencia polarizada es un procedimiento rápido y fiable que puede ser de gran utilidad para el análisis de rutina de los niveles de Homocisteína plasmática (AU)

Plasma homocysteine levels in renal transplanted patients on cyclosporine or tacrolimus therapy: effect of treatment with folic acid.

Hyperhomocysteinemia, an independent risk cardiovascular factor, has been reported in renal transplanted patients (RTP). The aim of the present study was to evaluate homocysteine levels in RTP treated with cyclosporine or tacrolimus, and the changes observed in the two groups of patients after treatment with folic acid. Forty-two RTP with stable function (21 treated with cyclosporine and 21 with tacrolimus, matched by gender and age) were studied. Forty healthy control subjects were matched by age and gender with the patients. In RTP, homocysteine was increased compared with the controls (16.4 +/-5.2 vs 8.0 +/- 1.8 micromol/L; p < 0.001), but there was no difference in vitamin B12 and folic acid levels. Thirty-three patients and one control showed hyperhomocysteinemia (78.5 vs 2.5%; p < 0.001). Homocysteine correlated negatively with creatinine clearance in the patients (p = 0.04), but no correlation was found with vitamin B12, folic acid and lipoproteins. By univariate analysis, patients treated with cyclosporine had higher homocysteine than those treated with tacrolimus (p = 0.03), but multivariate analysis did not confirm these results. In 21 patients with hyperhomocysteinemia and folate levels similar to those of the controls, folic acid (5 mg/d for 3 months) was administered. Homocysteine decreased significantly (19.1 +/- 4.8 vs 13.2 +/- 3.4 micromol/L; p < 0.001), with a median reduction of 31% and with no differences observed in patients treated with either cyclosporine or tacrolimus. We concluded that hyperhomocysteinemia is very frequent in RTP, but homocysteine levels are not different in patients treated with cyclosporine or tacrolimus. Folic acid therapy produces a significant decrease in homocysteine concentrations, in the absence of clear folate deficiency, without differences in relation to immunosuppressant therapy.

[Hyperhomocysteinemia is frequent in coronary disease patients. Study of 202 patients]. / La hiperhomocisteinemia es frecuente en pacientes con enfermedad coronaria. Estudio de 202 enfermos.

BACKGROUND: Previous studies have found that hyperhomocysteinemia is an independent risk factor for coronary disease. Homocysteine levels, and factors involved in their increase, are unknown in Spanish patients with coronary disease. PATIENTS AND METHODS: In 202 Spanish patients with coronary disease (174 men and 28 women) and age < 70 years old, homocysteine, creatinine, fibrinogen, lipoproteins, folic acid and vitamin B12 levels were determined. Controls were 40 healthy subjects whose age was not different from patients. RESULTS: Plasma homocysteine levels were increased in patients compared to controls (mean [SD] 11.7 [4.2], 95% confidence interval [CI]: 11.1-12.2, vs 8.4 [2.4], 95% CI: 7.7-9.2 mumol/l; p < 0.001). Hyperhomocysteinemia was found in 52 patients and in one control (26% vs 2.5%, odds ratio: 13.5, 95% CI: 1.8-100.8; p = 0.001). Homocysteine levels were positively associated in patients with creatinine level and negatively associated with folic acid level (p = 0.02 for both), but association with age, gender, fibrinogen, lipoproteins and vitamin B12 was not found. By multivariate analysis, folic acid was the only independent variable related with homocysteine levels (odds ratio: 0.32%, 95% CI: 0.122-0.882). In a subgroup of 30 patients with a low profile of cardiovascular risk (total-cholesterol < 225 mg/dl, nonsmokers and without diabetes and hypertension) an increase of homocysteine levels was also found, and 33% of them had hyperhomocysteinemia. CONCLUSION: Hyperhomocysteinemia was present in 26% of the patients with coronary disease. A similar percentage was found in the patients with a low profile of cardiovascular risk. Homocysteine levels were negatively associated with folic acid levels.

Implications of hypervitaminosis A on the calcium-phosphate metabolism and on blood lipids in hemodialysis.

Serum levels of vitamin A (VA) were measured in 71 hemodialysis (HD) patients and in 30 normal controls. 65 of the 71 patients were taking multivitamin preparations (MP) containing VA. The HD patients had significantly greater values: 7.81 +/- 2.86 mumol/l (224 +/- 82 micrograms/dl) versus 3.97 +/- 0.97 mumol/l (114 +/- 28 micrograms/dl; p less than 0.0005); those taking MP with large doses of VA showed the highest levels. Patients were divided as having normal (group I, n = 21) or elevated (group II, n = 50) serum levels of VA. Patients of group II had higher levels of serum calcium (Ca) and lower of serum phosphate (P) and PTH than those of group I. Four months after the withdrawal of oral VA, the serum levels of VA and Ca fell significantly in group II, while the serum P increased. On the contrary, in group I serum levels of VA, Ca and P remained unchanged. Serum triglycerides (TG) were significantly higher in group II but did not change after the withdrawal of VA. No differences between both groups of patients were observed for age, time on HD, residual diuresis, residual renal function, serum levels of cholesterol (CL) or anemia. A retrospective study of 18 hepatic biopsies of HD patients disclosed hyperplasia of Ito cells (VA-storaging cells) in 7 of them. These 7 biopsies belonged to patients who had taken large amounts of oral VA. Our data indicate that prolonged VA intake in HD patients is followed by an increase of serum CA, a decrease of serum P and PTH and a hepatic accumulation of VA.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic studies with 65Zn. X. Biosynthesis of alkaline phosphatase in cultures of Pseudomonas fluorescens.

Alkaline phosphatase from Pseudomonas fluorescens has been partially purified. Labelled 65ZnCl2 in the culture medium is incorporated in the most purified preparations. The enzyme shows a pH optimum of 7.2-7.5 and a Km value for p-nitrophenyl phosphate of 1 times 10(-4). Zinc ions at high concentration inhibit enzyme activity. The protective effect of Mg on the inactivation of alkaline phosphatase by heat is also reported.