Cytotoxic and interactive effects of zearalenone, alpha-zearalenol and beta-zearalenol and formation of metabolites in HepG2 cells / Citotoxicidad, formación de metabolitos e interacción entre zearalenona, alpha-zearalenol y beta-zearalenol en células HepG2

Zearalenone (ZEA) is a secondary metabolite of Fusarium fungi. ZEA is a non-steroidal estrogenic mycotoxin which is rapidly absorbed and metabolized to α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL) in the liver; therefore mixtures of these mycotoxins may be simultaneously present in biological systems and cause human health risk. The objectives of this study were: a) to compare the cytotoxicity of ZEA, α-ZOL and β-ZOL alone or in combination on human hepatoma (HepG2) cells using the MTT assay after 24, 48 and 72h of exposure, and b) to evaluate the interactions of these mycotoxins mixtures in HepG2 cell lines by the isobologram analysis. The IC50 values obtained for individual mycotoxins range from 70.0 to >100.0 µM, from 20.6 to 26.0 µM and from 38.4 to >100.0 µM in HepG2 cells for ZEA, α-ZOL and β-ZOL, respectively. Isobologram analysis provides a combination index (CI) value to determine the type of interaction that occurs. The interactions of ZEA and its metabolites showed slightly synergism (CI from 0.34±0.10 to 0.69±0.22) followed by additive effect (CI from 0.97±0.20 to 2.61±2.15) and turned into antagonism (CI from 1.29±0.18 to 7.77±2.27). The concentration of ZEA and its metabolites was determined with liquid chromatography coupled to the mass spectrometer detector-linear ion trap (LC-MS-LIT). No conversion of ZEA in α-ZOL and β-ZOL was detected. However other degradation products were detected (AU)

La zearalenona (ZEA) es un metabolito secundario producido por hongos del género Fusarium. ZEA es una micotoxina estrogénica no esteroidea que se metaboliza rápidamente en el hígado a α-zearalenol (α-ZOL) y β-zearalenol (β-ZOL); por lo tanto, mezclas de estas micotoxinas pueden estar presentes simultáneamente en un sistema biológico y causar un riesgo para la salud humana. Los objetivos de este estudio fueron: a) comparar la citotoxicidad de la ZEA, α-ZOL y β-ZOL de forma individual y en combinación en células hepáticas humanas (HepG2) usando el ensayo MTT tras una exposición de 24, 48 y 72h y b) evaluar la interacción de las mezclas de estas micotoxinas en células HepG2 mediante el análisis de las isobolas. Los valores de IC50 obtenidos en células HepG2 con las micotoxinas individuales van desde 70,0 a >100,0 µM, de 20,6 a 26,0 µM y de 38,4 a >100 µM para ZEA, α-ZOL y β-ZOL, respectivamente. El método de las isobolas proporciona el índice de combinación (IC) con el que se determina el tipo de interacción que se produce entre las micotoxinas. La interacción entre la ZEA y sus metabolitos mostró un ligero sinergismo (CI de 0,34±0,10 a 0,69±0,22), seguido de un efecto aditivo (CI de 0,97±0,20 a 2,61±2,15) que se acabó en antagonismo (CI de 1,29±0,18 a 7,77±2,27) dependiendo de la concentración y tiempo de exposición. La concentración de ZEA y sus metabolitos se determinó con cromatografía líquida acoplada a espectrometría de masas con trampa de iones lineal (LC-MS-LIT). No se detectó ninguna conversión de ZEA en α-ZOL y β-ZOL. Sin embargo se detectaron otros productos de degradación (AU)

[Relationship between tobacco smoke exposure and the concentrations of carboxyhemoglobin and hemoglobin]. / Relación entre la exposición al humo del tabaco y las concentraciones de carboxihemoglobina y hemoglobina.

To determine the carboxyhemoglobin (CO-Hb) predictive intervals in active and passive smokers and to obtain an equation expressing the relation of CO-Hb to number of cigarettes smoked, we studied 233 outpatients referred to an urban university hospital for arterial gas measurement. Patients were excluded if they were receiving oxygen therapy or had been hospitalized in the two months before the study. The patients were classified as non smokers (57), passive smokers (54), smokers of less than 11 cigarettes (22), smokers of 11 to 20 (41) smokers of 21 to 40 (44) and smokers of over 40 (15). All patients answered a questionnaire on exposure to tobacco smoke or other sources of CO. Blood gases and co-oximetry were measured in all patients. Mean CO-Hb and 95% confidence intervals were 1.53% (0.78-1.85%) in smokers and 2.59% (1.89-3.29%) in passive smokers. The linear equation that best expressed the relationship was CO-Hb = 0.153 x number of cigarettes + 1.1 exposure to other sources (1 or 0) + 1.39 (SD 0.84)%. Hemoglobin level was significantly higher in the two groups smoking more than 21 cigarettes. We conclude that the predictive intervals is 1.9% in non smokers who are not exposed to other sources of CO. Passive smokers have significantly higher levels of CO-Hb than non smokers. Heavy smokers have polycythemia.

[Prediction of exercise capacity after lung resection in patients with chronic airflow limitation]. / Predicción de capacidad de esfuerzo tras resección pulmonar en pacientes con limitación crónica al flujo aéreo.

To assess the usefulness of a method for predicting postoperative peak oxygen uptake based on lost lung function after lung resection (VO2peak-PPO) and to establish the underlying physiological foundation for the relation between VO2peak-PPO and the measured postoperative value VO2peak-PO), we studied 29 patients (26 men) [age 60 (SD9)] with chronic airflow limitation [FEV1 = 66 (SD13)%] undergoing lobectomy or major pulmonary resection to treat lung cancer. The patients were assigned to groups according to whether postoperative exercise tolerance was considered to be limited by exhaustion of ventilatory reserve (LV) or not (NLV). Data to estimate postoperative pulmonary function was obtained one week before surgery: patients performed pulmonary function tests and exercise tests on a treadmill; dyspnea was also evaluated and perfusion scintigraphs were obtained. Pulmonary function, exercise tolerance and dyspnea were evaluated again approximately five months after surgery. The mean difference between VO2peak-PPO and VO2peak-PO was -0.034 (CI 0.293 to -0.348) l.min-1 and the between-group correlation coefficient was 0.76. The correlation between VO2peak-PPO and VO2peak-PO was 0.86 (SE 0.1) [0.89 (SE 0.13) for LV (n = 14) patients and 0.85 (SE 0.16) for NLV (n = 15) patients]. The correlations after adjusting for preoperative VO2peak-PPO were 0.73 (SE 0.2) and 0.35 (SE 0.27) for LV and NLV patients, respectively. We conclude that VO2peak-PPO provides a valid but only moderately precise estimate of VO2peak-PO. Only in LV patients is there a true relation between a decrease in VO2peak and loss of lung function.

[Comparative study of 2 diagnostic tests of aspecific bronchial hyperreactivity]. / Estudio comparativo de dos pruebas de diagnóstico de la hiperreactividad bronquial inespecífica.

Bronchial challenge test are useful in diagnosis of bronchial hyperresponsiveness (BH). To assess the sensitivity of histamine test (HT) and exercise test (ET), 45 asthmatic patients (31 men, 14 women, ages 9-34) with normal resting pulmonary function test were studied. HT and ET were performed in two different days. HT was positive in 40 (6 severe, 23 moderate and 11 mild) and ET was positive in 13 (88.8% vr 28.8%, p < 0.001). All patients with positive ET had positive HT. There is a relationship between the degree of BH severity and the response to ET (chi 2 = 5.995; p < 0.05). The HT has a high profitability the diagnosis of BH. The ET has a low sensitivity.

Nasal continuous positive airway pressure in patients with COPD in acute respiratory failure. A study of the immediate effects.

The aim of this study was to assess the effect of nasal continuous positive airway pressure (CPAP) breathing on patients with COPD when they are in respiratory failure during acute episodes of the disease. We studied 15 male patients with COPD who were in acute, unstable condition, without mechanical ventilatory support, before and during 4 h of nasal CPAP. The respiratory rate decreased (initial, 30 +/- 6; final, 25 +/- 6; p < 0.001), as did the subjective sensation of dyspnea (initial Borg index, 3 +/- 3; final, 2 +/- 2; p < 0.05). A significant decrease in the average PaCO2 (before, 73 +/- 10 mm Hg; after, 61 +/- 9 mm Hg; p < 0.001) and a significant increase in the PaO2 (before, 57 +/- 13 mm Hg; after 64 +/- 14 mm Hg; p < 0.05) were also observed. Nasal CPAP was generally well tolerated. According to these results, nasal CPAP should be considered as a possibility for treatment in patients with COPD who are in acute respiratory failure, in order to avoid mechanical ventilation.

[The blood rheology of diuretics]. / Hemorreología de los diuréticos.

We have studied a group of 33 (27 female and 6 male) patients suffering pure essential arterial hypertension, with a mean age of 54.06 years, and who received a daily monodose of chlortalidone. Arterial pressure, blood viscosity at different shearing levels, as well as those parameters capable of modifying this viscosity were determined at days 0, 30, 60, 90, and 180 of treatment. Similarly, blood viscosity in this group of patients on day 0 is compared to a normotense control group. We observed a statistically significant (p less than 0.05) increase in blood viscosity in the hypertense group at day 0 when compared to the control group. No significant changes due to treatment could be observed in blood viscosity or any of the parameters studied. However, there was a significant decrease (p less than 0.0001) in arterial blood viscosity. "Chronic" treatment of essential hypertense patients have an inherent increase in blood viscosity. "Chronic" treatment of essential arterial hypertension with diuretics (chlortalidone) does not modify the hematocrit nor other biochemical parameters studies, nor blood viscosity. Treatment normalises blood pressure levels, but it does not "primarily" hemodynamically prevent ischemic events at the microcirculatory level.