Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse / Avaliação genotóxica e citotóxica da venlafaxina em ensaio agudo e subcrônico em camundongos

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse.

The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Síndrome de Moebius: ¿misoprostol como teratógeno? / Möbius syndrome: misoprostol as a teratogenic?

El síndrome de Moebius (SM) es una alteración congénita poco frecuente, caracterizada por la parálisis del nervio facial y del motor ocular externo, asociada a otras malformaciones craneofaciales y musculoesqueléticas. Su etiología no está clara, aunque en su aparición se asocian algunos agentes teratógenos, como el misoprostol. El mecanismo etiopatogénico se explicaría por la disrupción vascular secundaria al efecto vasoconstrictor del fármaco, en el territorio troncoencefálico. A continuación se describe el caso de un recién nacido afectado de SM, cuya madre usó misoprostol con fines abortivos durante el primer trimestre de la gestación. En los últimos años se ha documentado un número cada vez mayor de casos de SM asociados a esta práctica (AU)

The Möbius syndrome (Moebius syndrome) is an infrequent congenital disorder characterized by facial and abducens nerve palsy as well as the external ocular motor palsy. It is associated with other craniofacial and orthopedic anomalies. Its etiology is still unclear, although in its appearance teratogenics agents such as misoprostol have been related. Misoprostol’s etiopathogenic mechanism would be explained due to a secondary vascular disruption due to the vasoconstrictor effect of the medication, in the level of the area of the brain stem. Here we report a newborn with the Möbius syndrome whose mother had used misoprostol as an abortive during the first trimester of pregnancy. There has been a large number of Möbius syndrome associated with the use of misoprostol due to abortion attempt during the last years (AU)

Aminograma plasmático en lactantes intervenidos de una cardiopatía congénita compleja / Plasma aminogram in infants operated on complex congenital heart disease

La morbilidad postoperatoria de las cardiopatías congénitas intervenidas en edades tempranas sigue siendo elevada. A ello contribuyen tanto la malnutrición preoperatoria como las repercusiones de la respuesta sistémica a la agresión, incluyendo la circulación extracorpórea. Se ha estudiado poco el metabolismo proteico en estos lactantes y niños pequeños y su repercusión sobre resultados clínicos. El objetivo de este estudio fue evaluar el efecto de la Cirugía sobre el aminograma plasmático de lactantes intervenidos precozmente de una cardiopatía congénita compleja. Pacientes y métodos: Se recogieron de forma prospectiva los datos antropométricos y analíticos de 55 niños < 3 años sometidos a cirugía cardíaca electiva el día de la intervención y los días +1 (n = 53), +3 (n = 39) y +7 (n = 19). Los datos se presentan como media y desviación estándar. La comparación entre variables a lo largo del tiempo se realizó con un análisis de la varianza de una cola para muestras repetidas. Se consideró como estadísticamente significativo cuando p < 0,05. Resultados: La edad media en el momento de la cirugía fue de 5,5 ± 7,2 meses (rango 3 días a 3 años). La puntuación z para el peso antes de la cirugía fue de -1,24 ± 1,14 y para la longitud de -0,73 ± 1,53. Presentaban hipoprealbuminemia en el día 0 el 86,7% de los pacientes. Todos los valores de aminoácidos en plasma se encontraban como media dentro del rango de los valores normales. La evolución del aminograma mostró una disminución generalizada respecto al valor previa a la cirugía en el día +1 (p < 0,005) que permanecía disminuido en el día +3 para isoleucina, alanina, arginina, glicina, treonina y glutamina (p < 0,005) y sólo para glutamina en el día +7. Conclusiones: 1. El aminograma plasmático en lactantes con cardiopatía congénita se encontraba en rango de normalidad antes de la cirugía con independencia del estado nutricional. 2. Tras la cirugía se observa un descenso significativo de las concentraciones plasmáticas de la mayoría de los aminoácidos con tendencia a la normalización posterior, más lenta para algunos de los aminoácidos ramificados pero, sobre todo, para la glutamina. 3. La significación clínica de estos hallazgos merece un estudio más detallado (AU)

Post-surgical morbidity of congenital heart disease operated at early ages still is high. Both pre-surgical malnourishment and the repercussions of the systemic response to the aggression, including extracorporeal circulation contribute to it. The metabolism of proteins has been little studied in these infants and toddlers, as well as its repercussion on clinical outcomes. The aim of this study was to assess the effect of the surgery on the plasma aminogram of infants early operated for complex congenital heart disease. Patients and methods: We prospectively gathered the anthropometrical and analytical data of 55 children < 3 years of age submitted to elective heart surgery at the day of intervention and at days +1 (n = 53), +3 (n = 39), and +7 (n = 19). The data are presented as mean and standard deviation. The comparison between the variables through time was done by one-tailed analysis of variance for repeated samples. It was considered to be statistically significant with a p value < 0.05. Results: Mean age at the time of surgery was 5.5 ± 7.2 months (range 3 days-3 years). The z score for weight before the surgery was -1.24 ± 1.14 and for height -0.73 ± 1.53. 86.7% of the patients had hypo-prealbuminemia at day 0. The average plasma levels for all the amino acids were within the normal ranges. The evolution of the aminogram showed a general decrease as compared to the levels prior to surgery at day +1 (p < 0.005), which were kept low at +3 for isoleucine, alanine, arginine, glycine, threonine and glutamine (p < 0.005) and only for glutamine at day +7. Conclusions: 1. The plasma aminogram in infants with congenital heart disease was within the normal range before the surgery, irrespective of the nutritional status. 2. After the surgery, a significant decrease is observed for plasma levels of most of the amino acids, with a trend towards normalization, which is slower for certain branched amino acids, particularly for glutamine. 3. The clinical significance of these findings deserves further studies (AU)

Hyperhomocysteinemia and methylenetetrahydrofolate reductase 677C-->T and 1298A-->C mutations in patients with inflammatory bowel disease.

BACKGROUND: Hyperhomocysteinemia has been recently described in patients with inflammatory bowel disease (IBD), that could be related to the increased risk for thrombosis that exists in this disease. The aim of this study was the assessment of hyperhomocysteinemia in patients with IBD and its relation among vitamin B12 and folate levels, and methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C mutations. PATIENTS AND METHODS: Fifty two consecutive patients with IBD were studied (29 women and 23 men); age: mean (standard deviation 41.7 [11.9] years) and 186 controls with no difference in age and gender. Hyperhomocysteinemia was considered as homocysteine levels higher than mean plus two standard deviations of the control group (> or = 13 micromol/l). RESULTS: patients had an elevated prevalence of hyperhomocysteinemia (17.3 vs. 3.7%; p = 0.002) and lower folate (7.6 [4.1] vs. 8.9 [3.7] ng/ml; p = 0.01) and B12 vitamin levels (499 [287] vs. 603 [231] pg/ml; p = 0.003). Homocysteinemia was higher (14.3 [5.8] vs. 9.1 [3.9] micromol/l; p = 0.006) in 6 patients (11.5%) that had suffered thromboembolism. Frequency of MTHFR 677C-->T (13.5 vs. 11.3%; p = 0.66) and 1298A-->C (7.8 vs. 7.0%; p = 0.76) mutations was not increased in patients. Odds ratio (OR) for IBD in hyperhomocysteinemic patient was 5.51, 95% confidence interval (CI), 1.81-16.76; p = 0.002). Hyperhomocysteinemia was negatively associated with feminine gender (OR 0.08, 95% CI 0.01-0.49; p = 0.006) and folate levels (OR 0.04, 95%CI: 0.007-0.20; p < 0.001). CONCLUSIONS: hyperhomocysteinemia is associated with IBD and low folate levels, and could be involved in development of thromboembolism. MTHFR 677C-->T and 1298A-->C mutations are not related with the disease.

[Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia]. / Tromboembolia venosa e hiperhomocisteinemia como primera manifestación de una anemia perniciosa.

INTRODUCTION AND OBJECTIVE: Hyperhomocysteinemia is associated to thrombosis and atherosclerosis. Vitamin B12 is among its main causes and may be due to a pernicious anemia. This study aimed to know the prevalence of this disease in patients who have venous thromboembolism and hyperhomocysteinemia. PATIENTS AND METHODS: A total of 80 consecutive patients (55 men and 25 women; age: mean [standard deviation] 63 [15] years) with pulmonary embolism and/or venous thrombosis and elevated values of homocysteine (> 12 micromol/l) were studied. RESULTS: Pernicious anemia was diagnosed (positive Schilling test, presence of anti-intrinsic factor antibodies and/or anti-parietal cells and fundal atrophic gastritis) in 5 patients (6.25% with range of age: 42-73 years. Only one of them had macrocytic anemia and there were no alterations in any of them in the thrombophilia study. The patients were treated with vitamin B12, administering it orally (1 mg/day) in 4 of them. The homocysteine and vitamin B12 values were normalized in every case at 6 months. CONCLUSIONS: Although the prevalence of pernicious anemia is not elevated in patients with venous thromboembolism and hyperhomocysteinemia, its existence must be ruled out to avoid other thrombotic and neurological complications.

Tromboembolia venosa e hiperhomocisteinemia como primera manifestación de una anemia perniciosa / Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia

Fundamento y objetivo. La hiperhomocisteinemia se asocia a trombosis y aterosclerosis. Entre sus principales causas está la deficiencia de vitamina B12, que puede deberse a una anemia perniciosa. El objetivo del estudio ha sido conocer la prevalencia de esta enfermedad en los pacientes que presentan tromboembolia venosa e hiperhomocisteinemia. Pacientes y método. Se estudiaron consecutivamente 80 pacientes (55 varones y 25 mujeres; edad: media [desviación estándar]: 63 [15] años) con embolia pulmonar y/o trombosis venosa y valores elevados de homocisteína (> 12 µmol/l). Resultados. En 5 pacientes (6,25%), con rango de edad: 42-73 años se diagnosticó una anemia perniciosa (prueba de Schilling positiva, presencia de anticuerpos antifactor intrínseco y/o anticélulas parietales y gastritis atrófica fúndica). Sólo uno de ellos tenía anemia macrocítica y en ninguno existían otras alteraciones en el estudio de trombofilia. Los pacientes se trataron con vitamina B12, administrándosela a 4 de ellos por vía oral (1 mg/día), y en todos los casos se normalizaron a los 6 meses los valores de homocisteína y de vitamina B12. Conclusiones. En los pacientes con tromboembolia venosa e hiperhomocisteinemia, aunque la prevalencia de anemia perniciosa no es elevada, es necesario descartar su existencia para evitar otras complicaciones trombóticas y neurológicas

Introduction and objective. Hyperhomocysteinemia is associated to thrombosis and atherosclerosis. Vitamin B12 is among its main causes and may be due to a pernicious anemia. This study aimed to know the prevalence of this disease in patients who have venous thromboembolism and hyperhomocysteinemia. Patients and methods. A total of 80 consecutive patients (55 men and 25 women; age: mean [standard deviation] 63 [15] years) with pulmonary embolism and/or venous thrombosis and elevated values of homocysteine (> 12 µmol/l) were studied. Results. Pernicious anemia was diagnosed (positive Schilling test, presence of anti-intrinsic factor antibodies and/or anti-parietal cells and fundal atrophic gastritis) in 5 patients (6.25% with range of age: 42-73 years. Only one of them had macrocytic anemia and there were no alterations in any of them in the thrombophilia study. The patients were treated with vitamin B12, administering it orally (1 mg/day) in 4 of them. The homocysteine and vitamin B12 values were normalized in every case at 6 months. Conclusions. Although the prevalence of pernicious anemia is not elevated in patients with venous thromboembolism and hyperhomocysteinemia, its existence must be ruled out to avoid other thrombotic and neurological complicationsIntroduction and objective. Hyperhomocysteinemia is associated to thrombosis and atherosclerosis. Vitamin B12 is among its main causes and may be due to a pernicious anemia. This study aimed to know the prevalence of this disease in patients who have venous thromboembolism and hyperhomocysteinemia. Patients and methods. A total of 80 consecutive patients (55 men and 25 women; age: mean [standard deviation] 63 [15] years) with pulmonary embolism and/or venous thrombosis and elevated values of homocysteine (> 12 µmol/l) were studied. Results. Pernicious anemia was diagnosed (positive Schilling test, presence of anti-intrinsic factor antibodies and/or anti-parietal cells and fundal atrophic gastritis) in 5 patients (6.25% with range of age: 42-73 years. Only one of them had macrocytic anemia and there were no alterations in any of them in the thrombophilia study. The patients were treated with vitamin B12, administering it orally (1 mg/day) in 4 of them. The homocysteine and vitamin B12 values were normalized in every case at 6 months. Conclusions. Although the prevalence of pernicious anemia is not elevated in patients with venous thromboembolism and hyperhomocysteinemia, its existence must be ruled out to avoid other thrombotic and neurological complications

Hiperhomocisteinemia y mutaciones de la metilentetrahidrofolato reductasa 677C→ T y 1298A→ C en pacientes con enfermedad inflamatoria intestinal / Hyperhomocysteinemia and methylenetetrahydrofolate reductase 677→T and 1298A→ mutations in patients with inflammatory bowel disease

Fundamento: recientemente se ha descrito la existencia de hiperhomocisteinemia en la enfermedad inflamatoria intestinal(EII), que podría estar relacionada con el mayor riesgo de trombosisen esta enfermedad. El objetivo del estudio ha sido evaluar la hiperhomocisteinemia en los pacientes con EII y su relación con las concentraciones de vitamina B12 y folato séricos y con las mutacionesde la metilentetrahidrofolato reductasa (MTHFR)677C→T y 1298A→C.Pacientes y métodos: se estudiaron consecutivamente 52 pacientes con EII (29 mujeres y 23 varones; edad: media [desviación estándar] 41,7 [11,9] años) y 186 controles con edad y sexo similares. Se consideró hiperhomocisteinemia cuando los valoresde homocisteína eran superiores a la media más dos desviacionesestándar del grupo control (≥ 13 µmol/l).Resultados: los pacientes presentaban una mayor prevalenciade hiperhomocisteinemia (17,3 frente a 3,7%; p = 0,002) yunos valores más bajos de folato (7,6 [4,1] frente a 8,9 [3,7]ng/ml; p = 0,01) y de vitamina B12 (499 [287] frente a 603 [231]pg/ml; p = 0,003). En 6 pacientes (11,5%) que habían padecidoepisodios tromboembólicos la homocisteinemia era más elevada(14,3 [5,8] frente a 9,1 [3,9] µmol/l; p = 0,006). La frecuenciade las mutaciones MTHFR 677C→T (13,5% frente a 11,3%; p= 0,66) y de la 1298A→C (7,8 frente a 7,0%; p=0,76) no fuemayor en los pacientes. La odds ratio (OR) de EII en los pacienteshiperhomocisteinémicos fue 5,51, intervalo de confianza [IC]del 95%: 1,81-16,76; (p = 0,002). La hiperhomocisteinemia seasoció negativamente con el sexo femenino (OR 0,08, IC del95%, 0,01-0,49; p = 0,006) y con los valores de folato (OR0,04,IC del 95%: 0,007-0,20; p < 0,001).Conclusiones: la hiperhomocisteinemia se asocia a la EII y alas concentraciones bajas de folato, y puede estar implicada en eldesarrollo de tromboembolia. Las mutaciones MTHFR 677C→ Ty 1298A→ C no se relacionan con la enfermedad

Background: hyperhomocysteinemia has been recently describedin patients with inflammatory bowel disease (IBD), thatcould be related to the increased risk for thrombosis that exists inthis disease. The aim of this study was the assessment of hyperhomocysteinemiain patients with IBD and its relation among vitaminB12 and folate levels, and methylenetetrahydrofolate reductase(MTHFR) 677C→ T and 1298A→C mutations.Patients and methods: fifty two consecutive patients withIBD were studied (29 women and 23 men); age: mean (standarddeviation 41.7 [11.9] years) and 186 controls with no differencein age and gender. Hyperhomocysteinemia was considered as homocysteinelevels higher than mean plus two standard deviationsof the control group (≥ 13 µmol/l).Results: patients had an elevated prevalence of hyperhomocysteinemia(17.3 vs. 3.7%; p = 0.002) and lower folate (7.6[4.1] vs. 8.9 [3.7] ng/ml; p = 0.01) and B12 vitamin levels (499[287] vs. 603 [231] pg/ml; p = 0.003). Homocysteinemia washigher (14.3 [5.8] vs. 9.1 [3.9] µmol/l; p = 0.006) in 6 patients(11.5%) that had suffered thromboembolism. Frequency of MTHFR677C→T (13.5 vs. 11.3%; p = 0.66) and 1298A→C (7.8 vs.7.0%; p = 0.76) mutations was not increased in patients. Odds ratio(OR) for IBD in hyperhomocysteinemic patient was 5.51, 95%confidence interval (CI), 1.81-16.76; p = 0.002). Hyperhomocysteinemiawas negatively associated with feminine gender (OR0.08, 95% CI 0.01-0.49; p = 0.006) and folate levels (OR 0.04,95%CI: 0.007-0.20; p < 0.001).Conclusions: hyperhomocysteinemia is associated with IBDand low folate levels, and could be involved in development ofthromboembolism. MTHFR 677C→T and 1298A→C mutationsare not related with the disease

[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.

Desarrollo de un nuevo método cromatográfico de intercambio iónico para la determinación de homocisteína total en plasma / An improved ion-exchange chromatographic method to determine total homocysteine levels in plasma

La medida de la concentración de la homocisteína total en plasma es de gran utilidad como marcador de riesgo cardiovascular. Las técnicas convencionales para su medición plasmática están basadas en métodos de HPLC, aunque últimamente se han desarrollado técnicas de inmunoensayo. El objetivo de nuestro estudio fue establecer un procedimiento rápido y exacto de cromatografía de intercambio iónico para determinar la homocisteína total en plasma en un analizador convencional de aminoácidos, utilizando ninhidrina como reactivo de detección. Asimismo, hemos establecido el intervalo de referencia para la homocisteína y metionina en plasma en una población de adultos sanos. Los coeficientes de variación intra e interserie oscilaron entre 1,6 y 4,6 por ciento. El límite de detección obtenido fue de 0,75 micromol/L. La media de las recuperaciones obtenidas fue de 98,5 +/- 5,2 para la homocisteína y de 101,7 +/- 4,6 para la homocisteína. El intervalo de referencia establecido para la población de adultos sanos (120 controles de edad media: 44,7+/- 12,4) fue de 3,13 a 12,01 micromol/L para la concentración plasmática de homocisteína y de 14,16 a 33,08 micromol/L para la metionina (AU)

[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.