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.

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.

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.

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.

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 (≥ 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 was higher (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 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.

Fundamento: recientemente se ha descrito la existencia de hiperhomocisteinemia en la enfermedad inflamatoria intestinal (EII), que podría estar relacionada con el mayor riesgo de trombosis en 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 mutaciones de 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 valores de homocisteína eran superiores a la media más dos desviaciones estándar del grupo control (≥ 13 mmol/l). Resultados: los pacientes presentaban una mayor prevalencia de hiperhomocisteinemia (17,3 frente a 3,7%; p = 0,002) y unos 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 padecido episodios tromboembólicos la homocisteinemia era más elevada (14,3 [5,8] frente a 9,1 [3,9] µmol/l; p = 0,006). La frecuencia de 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 fue mayor en los pacientes. La odds ratio (OR) de EII en los pacientes hiperhomocisteinémicos fue 5,51, intervalo de confianza [IC] del 95%: 1,81-16,76; (p = 0,002). La hiperhomocisteinemia se asoció negativamente con el sexo femenino (OR 0,08, IC del 95%, 0,01-0,49; p = 0,006) y con los valores de folato (OR 0,04,IC del 95%: 0,007-0,20; p < 0,001). Conclusiones: la hiperhomocisteinemia se asocia a la EII y a las concentraciones bajas de folato, y puede estar implicada en el desarrollo de tromboembolia. Las mutaciones MTHFR 677C→ T y 1298A→ C no se relacionan con la enfermedad.