The Time between Paraquat Ingestion and a Negative Dithionite Urine Test in an Independent Risk Factor for Death and Organ Failure in Acute Paraquat Intoxication

To identify a prognostic marker that is less sensitive to variations in the elapsed time since paraquat ingestion, we assessed the time between paraquat ingestion and a negative dithionite urine test as a prognostic parameter in patients with acute paraquat intoxication. Forty-one patients with acute paraquat intoxication were enrolled in this study and analyzed to verify significant determinants of mortality and organ dysfunction. The amount of paraquat ingested, paraquat plasma levels, and the time to a negative urine dithionite test were significant independent risk factors predicting mortality. The amount of paraquat ingestion, and the time to a negative urine dithionite test were independent risk factors predicting organ dysfunction. With a cut-off value of 34.5 hr for the time to negative conversion of the urine dithionite test, the sensitivity and specificity for mortality were 71.4% and 75.0%, respectively. The incidence of acute kidney injury and respiratory failure above 34.5 hr were 100% and 85.0%, respectively. In conclusion, the time to a negative urine dithionite test is the reliable marker for predicting mortality and/or essential organ failure in patients with acute paraquat intoxication, who survive 72 hr.

Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 Levels in Patients with Acute Paraquat Intoxication

To investigate the effects of reactive oxygen species (ROS) on tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) plasma levels, and their possible implications on clinical outcome, we measured tPA and PAI-1 levels in 101 patients with acute paraquat (PQ) intoxication. The control group consisted of patients who ingested non-PQ pesticides during the same period. tPA and PAI-1 levels were higher in the PQ group than in the controls. PQ levels were significantly correlated with ingested amount, timelag to hospital, tPA level, and hospitalization duration. tPA levels were correlated with PAI-1, fibrin degradation product (FDP), and D-dimer. D-dimer levels were lower in the PQ group than in the controls. Univariate analysis indicated the following significant determinants of death: age, ingested amount, PQ level, timelag to hospital, serum creatinine, lipase, pH, pCO2, HCO3-, WBC, FDP, PAI-1, and tPA. However, multivariate analysis indicated that only PQ level was significant independent factor predicting death. In conclusion, tPA and PAI-1 levels were higher, while D-dimer levels were lower in the PQ group than in the controls, implying that ROS stimulate tPA and PAI-1, but PAI-1 activity overrides tPA activity in this setting. Decreased fibrinolytic activity appears to be one of the clinical characteristics of acute PQ intoxication.

The Area of Ground Glass Opacities of the Lungs as a Predictive Factor in Acute Paraquat Intoxication

Even though plasma paraquat (PQ) levels have known to be an informative predictor, many patients succumb at low PQ levels in acute PQ intoxication. This study was designed to see whether the high resolution computerized tomography (HRCT) of the lungs would be a predictive measure in acute PQ intoxication. HRCT of the lungs was obtained from 119 patients with acute PQ intoxication on 7 days after PQ ingestion. The areas with ground glass opacities (GGOs) were evaluated at five levels with the area measurement tool of the picture archiving and communication systems. Among 119 patients, 102 survived and 17 died. The plasma PQ levels were significantly higher in the non-survivors than in the survivors (2.6+/-4.0 microgram/mL vs. 0.2+/-0.4 microgram/mL, P=0.02). The area with GGOs was 2.0+/-6.4% in the survivors and 73.0+/- 29.9% in the non-survivors (P<0.001). No patients survived when the area with GGOs was more than 40% but all of the patients survived when the area affected by GGOs was less than 20%. In conclusion, the area of GGOs is a useful predictor of survival in acute PQ intoxication, especially in patients with low plasma PQ levels.

Citotoxicidad del glifosato en células mononucleares de sangre periférica humana / Cytotoxicity of the herbicide glyphosate in human peripheral blood mononuclear cells

Introducción. El glifosato es un herbicida de amplio espectro, no selectivo, utilizado comúnmente en agricultura para eliminar malezas. Los estudios que han evaluado la toxicidad del glifosato en animales y en ambiente muestran que las formulaciones comerciales son más tóxicas que el componente activo. Objetivos. Evaluar la toxicidad del glifosato grado técnico y de la formulación comercial Roundup® en células mononucleares de sangre periférica humana. Materiales y métodos. Células mononucleares de sangre periférica humana fueron expuestas a diferentes concentraciones de glifosato en grado técnico y en la forma de Roundup® por 24, 48, 72 y 96 horas. La citotoxicidad se evaluó mediante el método de exclusión con azul de tripano y reducción del reactivo sal sódica de (2,3-bis[2-metoxi-4-nitro-5-sulfofenil]-2Htetrazolio-5-carboxianilida) (XTT). Resultados. Ambas presentaciones del glifosato (grado técnico y Roundup®) fueron tóxicas para las células mononucleares de sangre periférica humana. Roundup® fue más citotóxico que el glifosato grado técnico, ya que se encontró que la concentración letal 50 (LC50) analizada con el método de exclusión con azul de tripano a las 24 horas fue de 56,4 µg/ml de glifosato en la forma de Roundup® y de 1.640 mg/ml (1,64 µg/ml) para glifosato grado técnico. Conclusiones. Los resultados de este estudio in vitro confirman el efecto tóxico para las células humanas observado para el glifosato y sus preparaciones comerciales, y que estas últimas son más citotóxicas que el compuesto activo, lo que apoya la idea de que los aditivos presentes en las formulaciones comerciales juegan un papel crucial en la toxicidad atribuida a los herbicidas que contienen glifosato.

Introduction. Glyphosate is a broad-spectrum, non-selective herbicide and commonly used to eliminate weeds in agricultural and forest settings. Studies evaluating glyphosate toxicity in animals and environment show that commercial formulations of glyphosate are more toxic than the active component itself. Objectives. Technical grade glyphosate was compared with the commercial formulation Roundup® in their respective toxicities on human peripheral blood mononuclear cells. Materials and methods. Human peripheral blood mononuclear cells were exposed to different concentrations of glyphosate, either technical grade or in the form of Roundup for 24 h, 48 h, 72 h, and 96 h. Cytotoxicity was assayed by trypan blue dye exclusion method and reduction of (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2Htetrazolium-5-carboxyanilide inner salt) XTT reagent. Results. Both technical grade glyphosate and Roundup® formulation were toxic to human peripheral blood mononuclear cells. Cytotoxicity of Roundup® was higher than cytotoxicity of glyphosate, since the LC50 (50% lethal concentration) determined by the trypan blue exclusion method at 24 h was the equivalent of 56.4 ìg/ml of glyphosate in the form of Roundup® and 1,640 ìg/ml (1.64 mg/ml) for technical grade glyphosate. Conclusions. This in vitro study confirmed the toxic effects on human cells by glyphosate and its commercial preparations. Commercial formulations were more cytotoxic than the active component alone, supporting the concept that additives in commercial formulations play a role in the toxicity attributed to glyphosate-based herbicides.