Intoxicación fatal con paraquat por vía dérmica. Reporte de caso / Fatal paraquat poisoning by dermal exposure. Case report

Introducción: Por su alta letalidad el paraquat® es utilizado con fines suicidas, siendo la principal vía de uso, la oral; los casos por vía cutánea son escasos y raras veces son fatales. Este reporte presenta un caso de compromiso sistémico severo y muerte después de exposición dérmica a paraquat® . Resumen del caso: Paciente femenina de 47 años, soltera, ama de casa, de procedencia rural, con secundaria incompleta; e historia de aplicación de paraquat® en ulcera. A las 24h de aplicación presento fiebre, vómito y malestar general; al ingreso hospitalario presento además ictericia generalizada, insuficiencia renal aguda, insuficiencia respiratoria, deterioro progresivo de su estado de salud y muerte, por lo que fue remitida a autopsia médico legal. Los hallazgos de autopsia descartaron la ingesta oral y mostraron páncreas hemorrágico, riñones congestivos, hígado de tamaño aumentado (2550g) y hemorrágico, corazón aumentado de tamaño. Los estudios histopatológicos mostraron daño alveolar difuso, (membranas hialinas, edema y hemorragia); neumonía en pulmón y congestión visceral generalizada...(AU)

Intoxicação cutânea grave por Paraquat / Serious skin poisoning by Paraquat

O Paraquat é um herbicida não seletivo altamente tóxico, sendo responsável por altas taxas de letalidade acidentais ou provocadas, devido, principalmente, à insuficiência respiratória. Apesar de a intoxicação por via oral ser a principal e mais grave, o contato prolongado com a substância em uma grande área corporal pode gerar uma toxicidade similar e levar ao óbito ­ fato pouco elucidado na literatura. Este é o relato de caso de um homem de 22 anos, que foi admitido em um hospital devido a queixas de mal-estar, náuseas, febre, cefaleia, dor abdominal, diarreia, queimaduras e dispneia. A suspeita diagnóstica inicial foi de hantavirose, leptospirose, dengue e tromboembolismo pulmonar e, posteriormente, foi comprovado intoxicação exógena com agrotóxico por via inalatória e cutânea. Exames de imagem revelaram fibrose pulmonar difusa e ele também apresentou alterações renais, hepáticas e coagulatórias. Como não há antídoto específico, foi empregado tratamento sintomático e suportivo, com uso de carvão ativado, antibióticos, corticoides, antioxidantes e hemodiálise. No entanto, o paciente teve uma piora progressiva do quadro, vindo a óbito devido à síndrome da angústia respiratória aguda e fibrose pulmonar. O Paraquat, embora proibido no Brasil em 2020, continua sendo utilizado de forma ilegal. Além disso, seu substituto, o Diquat, possui toxicidade semelhante. Assim, é fundamental que os profissionais da saúde reconheçam o diagnóstico da intoxicação por tais substâncias e suas diferentes vias de exposição. Também são necessárias novas medidas de fiscalização das substâncias e maior investimento em educação em saúde para evitar exposições acidentais, assim como relatado (AU).

Paraquat is a highly toxic non-selective herbicide and is responsible for high accidental or provoked lethality rates, mainly due to respiratory failure. Although oral poisoning is the primary and most severe, prolonged contact with the substance in a large body area can lead to similar toxicity and death ­ a fact that is little elucidated in the literature. This is the case report of a 22-year-old man admitted to a hospital due to complaints of malaise, nausea, fever, headache, abdominal pain, diarrhea, burns and dyspnea. The initial diagnostic suspicion was hantaviruses, leptospirosis, dengue and pulmonary thromboembolism, and there was subsequently proven exogenous intoxication with pesticides by inhalation and cutaneous route. Imaging tests revealed diffuse pulmonary fibrosis and he also had renal, hepatic and coagulation alterations. As there is no specific antidote, symptomatic and supportive treatment was performed using activated charcoal, antibiotics, corticosteroids, antioxidants and hemodialysis. However, the patient had a progressive worsening of the condition and died due to acute respiratory distress syndrome and pulmonary fibrosis. Paraquat, although banned in Brazil in 2020, continues to be used illegally. In addition, its substitute, the Diquat, has similar toxicity. Thus, it is essential that health professionals recognize the diagnosis of intoxication by such substances and their different exposure routes. New control measures for these substances and greater investment in health education are also needed to prevent accidental exposure, as reported (AU).

Dynamic changes of locus coeruleus damage in Parkinson's disease-like mice induced by paraquat / 中华劳动卫生职业病杂志

Objective: To observe the dynamic changes of brainstem locus coeruleus (LC) damage in Parkinson' s disease (PD) -like mice by paraquat (PQ) . Methods: In October 2019, 36 male C57BL/6 mice were randomly divided into the exposure group and the control group, with 18 mice in each group. The mice in the exposure group were given intraperitoneal injection of 15 mg/kg PQ, and the mice in the control group were given intraperitoneal injection of 0.9% saline, twice a week for 8 weeks. Neurobehavioral changes (pole climbing test, swimming test, open field test, tail hanging test, high plus maze test and water maze test) were observed at 4 weeks, 6 weeks and 8 weeks, respectively, and the changes of motor ability, emotion and cognitive function were evaluated. The brain tissue of mice were taken and stained with Hematoxylin-Eosin (HE) to observe the pathological changes of LC. Nissl staining was used to detect the changes of neuronal Nissl bodies in LC. Immunohistochemistry (IHC) staining was used to detect the expression of neuron nuclear antigen (NeuN) , dopamine (DA) neurons and norepinephrine (NE) neuron markers tyrosine hydroxylase (TH) , α-synuclein (α-syn) in substantia nigra (SN) and LC. The expression levels of NeuN, TH and α-syn in the midbrain and brainstem were detected by Western blotting. TUNEL staining was used to detect neuronal apoptosis in LC. Results: Compared with the 4th week of PQ exposure group, the time of pole climbing and swimming immobility were gradually increased, the ratio of open arm residence time of high plus maze test and the number of times of the platform and the residence time of platform quadrant in water maze test were gradually decreased (P<0.05) in the exposure group with the progress of exposure time. The results of HE and Nissl staining showed that the neurons in LC gradually arranged loosely, the nucleus were deeply stained, the cytoplasm was pyknosis, and the number of Nissl bodies gradually decreased (P<0.05) in the exposure group with the progress of exposure time. IHC results showed that the number of NeuN and TH positive cells in SN and LC of mice were gradually decreased, and the positive expression of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. Western blotting results showed that the expression levels of NeuN and TH in the midbrain and brainstem were gradually decreased, and the expression level of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. TUNEL staining showed that the apoptosis rates of neurons in LC were gradually increased (P<0.05) in the exposure group with the progress of exposure time. Conclusion: PQ induces progressive damage in the LC area of PD-like mice, which may be caused by the abnormal accumulation of pathological α-syn in the LC area.

Preliminary study on time-dependent changes of intestinal tract and brain-gut axis in mice model of Parkinson's disease induced by paraquat / 中华劳动卫生职业病杂志

Objective: To observe the intestinal time-dependent changes in Parkinson's disease (PD) mouse model constructed by intraperitoneal injection of paraquat (PQ) and to establish the brain-gut axis connection initially. Methods: In October 2019, 48 mice were randomly divided into treated group and control groups: treated 4-week (P-4) group, treated 6-week (P-6) group, treated 8-week (P-8) group, control 4-week (C-4) group, control 6-week (C-6) group, and control 8-week (C-8) group. The treated group was injected with 15 mg/kg PQ solution and the control group was injected with 0.9% saline (0.2 ml/20 g) by intraperitoneal injection twice a week. After the initial state (0 weeks) and the treatment at the end of 4, 6 and 8 weeks, the mood changes and motor functions of mice were assessed by neurobehavioral tests (open field test, pole climbing test, tail suspension test and elevated plus maze test) . And the number of fecal pellets for 1 h and water content were calculated to assess the functional status of the gastrointestinal tract. Western blotting experiments were performed to detect the expression levels of α-synuclein (α-syn) and tyrosine hydroxylase (TH) in the nigrostriatal region of the mouse brain, the tight junction markers zonula occludens-1 (ZO-1) and Occludin, the inflammatory markers of integrin αM subunit (CD11b) , inducible nitric oxide synthase (iNOS) , high mobility group box 1 (HMGB1) , interleukin-1β (IL-1β) , and the neuronal markers βⅢ-tubulin and α-syn protein in the colon.Immunohistochemical staining was performed to detect the expression levels of colonic tight junction proteins ZO-1 and Occludin. Immunofluorescence staining was performed to detect the expression levels of TH in the substantia nigra region of the midbrain, and the co-localization of colonic intestine neuronal marker (βⅢ-tubulin) and Ser129 α-syn in the colonic. Results: Compared with the initial state (0 weeks) and C-8 group, mice in the P-8 group had significantly higher pole climbing test scores and resting time, and significantly lower total active distance, mean active speed, percentage of open arm entry and 1 h fecal instances (P<0.05) . After poisoning, the 1 h fecal water content of model mice first increased and then decreased, the P-4 and P-6 groups were significantly higher than the simultaneous point control group, and the P-8 groups were significantly lower than the initial state (P<0.05) . Compared with control, P-4 and P-6 groups, the expression levels of ZO-1 and Occludin in the P-8 group were significantly decreased (P<0.05) . Compared with control group, the expression levels of CD11b and IL-1β in the P-4 group were significantly increased (P<0.05) . Compared with control and P-4 group, the expression levels of CD11b, iNOS, HMGB1 and IL-1β in the P-6 and P-8 groups were significantly increased (P<0.05) . Compared with the control and P-4 groups, the expression levels of βⅢ-tubulin in the colon of mice in the P-8 group were significantly decreased, and the expression levels of α-syn and Ser129 α-syn were significantly increased (P<0.05) . The expression level of Ser129 α-syn in the colon of model mice was negatively correlated with the expression level of βⅢ-tubulin (r(s)=-0.9149, 95%CI: -0.9771--0.7085, P<0.001) . Ser129 α-syn and βⅢ-tubulin co-localization in the colonic intermuscular plexus region increased gradually with the time of exposure. Compared with the control, P-4 and P-6 groups, the expression level of TH in the nigrostriatal region of the brain was significantly decreased, and the expression levels of α-syn and Ser129 α-syn were significantly increased in the P-8 group (P<0.05) . Correlation analysis showed that the relative expression level of Ser129 α-syn in the nigrostriatal region of the brain was negatively correlated with the expression level of TH in the model mice (r(s)=-0.9716, 95% CI: -0.9925--0.8953, P<0.001) . Conclusion: The PD mouse model is successfully established by PQ, and the intestinal function of the model mice is reduced in a time-dependent manner. And on this basis, it is preliminary determined that the abnormal aggregation of α-syn may be an important substance connecting the brain-gut axis.

Effects on extravascular lung water of lung protective ventilation strategy applied on piglets with acute respiratory distress syndrome induced by paraquat / 中华劳动卫生职业病杂志

Objective: To study the effects on extravascular lung water of lung protective ventilation strategy applying on piglets with acute respiratory distress syndrome (ARDS) induced by paraquat (PQ) under pulse indicating continuous cardiac output (PiCCO) monitoring. Methods: The piglets models with ARDS induced by PQ were established in June 2020 and all of them were received mechanical ventilation and divided into three groups according to tidal volume (V(T)) : small V(T) group (6 ml/kg) , middle V(T) group (10 ml/kg) and large V(T) group (15 ml/kg) , there were 5 piglets in each group. The positive end expiratory pressure (PEEP) were all setup on 10 cmH(2)O. The indexes such as arterial blood gas analysis, oxygenation index (OI) , extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI) were monitored at time of before the model was established (baseline) , time of the model was established (t(0)) and 2 h (t(2)) , 4 h (t(4)) , 6 h (t(6)) after mechanical ventilation. Lung tissue were punctured at time of baseline, t(0) and t(6) to be stained by Hematoxylin-eosin (HE) staining and pulmonary pathology were observed under light microscopy. Results: The heart rate (HR) , mean arterial pressure (MAP) and partial pressure of carbon dioxide (PaCO(2)) of all groups were higher than the base value while the pH values, partial pressure of oxygen (PaO(2)) and OI were lower than the base value when the models were established (P<0.05) . After mechanical ventilation, the HR and MAP values of all groups at t(2), t(4) and t(6) were lower than t(0) while the PaCO(2) of t(4) and t(6) were all higher than t(0), the differences were statistically significant (P<0.05) . The PaO(2) and OI of all groups showed a trend of rising at first and then decreasing after mechanical ventilation. The MAP, PaO(2), PaCO(2) and OI of the middle V(T) group and large V(T) group were apparently lower than that of the small V(T) group at t(2), t(4) and t(6) (P<0.05) . The ELWI and PVPI at t(0) of all groups were higher than that of baseline (P<0.05) . The ELWI of the small V(T) group at t(6) were lower than t(0) of the same group and t(6) of the middle V(T) group and large V(T) group (P<0.05) . HE staining showed congestion and edema of alveolar tissue, swelling of capillaries, exudation of red blood cells and widening of alveolar septum in piglets after successful modeling. And further widening of alveolar septum and rupture of alveolar septum could be seen in the lung tissues of each group at t(6), and the injury was the slightest in the small V(T) group. Conclusion: The lung protective ventilation strategy can alleviate the extravascular lung water and ARDS induced by PQ and improve oxygenation.

Testosterone antagonizes paraquat-induced cardiomyocyte senescence via the mIGF-1/SIRT1 signaling pathway

Testosterone has been demonstrated to antagonize doxorubicin-induced cardiomyocyte senescence. However, whether testosterone prevents the paraquat-induced cardiomyocyte senescence is largely unknown. The detection of SA-β-gal activity was performed using senescence β-gal staining kit and the reactive oxygen species levels were determined by reactive oxygen species assay kit. The plasmids for insulin-like growth factor 1 shRNA (sh-mIGF-1), sirtuin-1 shRNA (sh-SIRT1), scramble shRNA (sh-NC), overexpressing mIGF-1 (mIGF-1), overexpressing SIRT1 (SIRT1), and negative controls (NC) were obtained for this study. The expression of target genes was detected using quantitative real-time PCR, immunolabeling, and western blot. We found that testosterone significantly delayed the paraquat-induced HL-1 cardiomyocyte senescence as evidenced by decreasing senescence-associated β-galactosidase activity and reactive oxygen species generation, which were accompanied by the up-regulated expression of mIGF-1 and SIRT1. RNA interference to reduce mIGF-1 and SIRT1 expression showed that testosterone prevented paraquat-induced HL-1 senescence via the mIGF-1/SIRT1 signaling pathway. Furthermore, myocardial contraction was evaluated by expression of genes of the contractile proteins/enzymes, such as α-myosin heavy chain 6 (MHC6), α-myosin heavy chain 7 (MHC7), α-skeletal actin (ACTA-1), and sarco/endoplasmic reticulum calcium ATPase-2 (SERCA2). Testosterone adjusted the above four gene expressions and the adjustment was blocked by mIGF-1 or SIRT1 inhibition. Our findings suggested that the mIGF-1/SIRT1 signaling pathway mediated the protective function of testosterone against the HL-1 cardiomyocyte senescence by paraquat, which provided new clues for the mechanisms underlying the anti-aging role of testosterone in cardiomyocytes.

Efeito protetor da melatonina sobre intoxicações por herbicidas / Protective effect of melatonin on poisoning by herbicides

O uso inadequado de herbicidas pode resultar em intoxicações agudas e, às vezes, crônicas por exposição em longo prazo a baixos níveis desses agentes tóxicos, podendo o herbicida atuar também como agentes teratogênicos, mutagênicos, cancerígenos e desreguladores endócrinos, com o aparecimento de doenças neurodegenerativas e distúrbios reprodutivos. Estudos têm revelado que a melatonina tem propriedades antioxidantes, anti-inflamatórias e imunomoduladoras e atua na reprodução. Essa indolamina está entre os agentes que têm se mostrado benéfico em intoxicações por herbicidas, porém não há relatos do uso de melatonina contra intoxicações por Glifosato-Roundup®, muito menos em associação com o Paraquat. Dessa forma, o maior interesse no tratamento das intoxicações por herbicidas, tem-se concentrado em medidas que impeçam ou minimizem as lesões celulares provocadas nos diversos sistemas biológicos. Assim, a melatonina, como antioxidante conhecido, pode ser mais uma alternativa contra as intoxicações por herbicidas associados e/ou individuais.

The inadequate use of herbicides may cause serious and sometimes chronic poisoning due to long exposure to low levels of toxic agents. Herbicides may also be teratogenic, mutagenic, cancerigenous agents and endocrine disruptors, with the occurrence of neurodegenerative diseases and reproduction disorders. Several studies have shown that melatonin has antioxidant, anti-inflammatory and immune-modulating qualities, besides affecting the reproduction system. It is among the agents which are beneficent in poisoning by herbicides even though no reports are extant on the use of melatonin against poisoning by Glyphosate-Roundup® alone or associated with Paraquat. Solutions that prevent or minimize cell lesions caused by several biological systems have been focused upon in the treatment for poisoning with herbicides. Thus, melatonin, a known antioxidant, may be an alternative against the poisoning by single or associated herbicides.

Longterm melatonin administration alleviates paraquat mediated oxidative stress in Drosophila melanogaster / La administración de melatonina a largo plazo mitiga el estrés oxidativo mediado por paraquat en Drosophila melanogaster

We investigated the effect of melatonin (MEL) in the activities of cytosolic superoxide dismutase (SOD) and catalase as well as in the levels of H2O2 and mitochondrial malondialdehyde (MDA) in paraquat-intoxicated Drosophila melanogaster. Paraquat (40 mM) was administrated for 36 h. Three groups of flies intoxicated with paraquat were used: PQ (exposed during 36h to paraquat), PQ-MEL (exposed during 36h to paraquat and then treated with MEL [0.43 mM] for 12 days) and PQ-Control (maintained in standard corn meal for 12 days). Two additional groups without pre-intoxication with PQ were added: Control (maintained in standard corn meal) and MEL (treated with MEL for 12 days). Immediately after PQ intoxication the concentration of MDA (17.240 ± 0.554 nmoles MDA/mg protein) and H2O2 (3.313 ± 0.086 nmol hydrogen peroxide/mg protein) and the activities of SOD and catalase (419.667 ± 0.731 and 0.216 ± 0.009 Units/mg of protein, respectively) in the PQ group were significantly increased with respect to Control. After 12 days of intoxication with PQ, the PQ-Control flies showed increases in H2O2 (4.336 ± 0.108) and MDA levels (8.620 ± 0.156), and in the activities of SOD and catalase (692.570 ± 0.433 and 0.327 ± 0.003, respectively) as compared to PQ-MEL (p<0.001). Treatment with MEL extended the life span of the groups PQ-MEL and MEL when compared to their corresponding controls. Motor activity decreased significantly in PQ-Control and PQ-MEL flies, suggesting that the damage caused by PQ affected the nervous system of flies. Our findings showed that oxidative damage caused by paraquat was observed even after 12 days and that melatonin mitigates this damage.

Investigamos el efecto de la melatonina (MEL) en la actividad de la superóxido dismutasa citosólica (SOD) y la catalasa, así como en las concentraciones del H2O2 y del malondialdehido mitocondrial (MDA) en la toxicidad inducida por paraquat (PQ) en Drosophila melanogaster. El paraquat (40 mM) fue administrado durante 36h. Tres grupos de moscas se utilizaron después de la intoxicación con paraquat: PQ (expuestas a paraquat durante 36 h), PQ-MEL (expuestas durante 36 horas a PQ y luego tratadas con MEL [0,43 mM] por 12 días) y PQ-Control (mantenidas en medio estándar por 12 días). Se incluyeron dos grupos adicionales sin pre-intoxicación con PQ: Control (mantenido en medio estándar) y MEL (tratado con MEL por 12 días). Inmediatamente después de la intoxicación con PQ, las concentraciones de MDA (17,240 ± 0,554 nmol de MDA/mg de proteína), H2O2 (3,313 ± 0,086 nmol de H2O2/mg de proteína) y las actividades de la SOD y catalasa (419,667 ± 0,731 y 0,216 ± 0,009 unidades/mg de proteína, respectivamente) se incrementaron significativamente con respecto al Control. Doce días después de la intoxicación con PQ, las moscas PQ-Control mostraron un aumento en la concentración de H2O2 (4,336 ± 0,108), de los niveles de MDA (8,620 ± 0,156) y en las actividades de la SOD y la catalasa (692,570 ± 0,433 y 0,327 ± 0,003, respectivamente) en comparación con el grupo PQ-MEL (p<0,001). El tratamiento con MEL extendió el tiempo de vida de los grupos PQ-MEL y MEL en comparación con sus correspondientes controles. La actividad motora disminuyó significativamente en las moscas de los grupos PQ-Control y PQ-MEL, lo que sugiere que el PQ afectó el sistema nervioso de las moscas. Nuestros hallazgos demostraron que el daño oxidativo causado por paraquat en las moscas fue observado aún después de 12 días de intoxicadas y que la melatonina logró mitigar este daño.

Intoxicación por Paraquat / Paraquat's poisoning

Se reporta dos pacientes que ingirieron dosis superiores de 30 mL de 1,1 -dimetil-4,4 bipirdilo dicloruro (Paraquat). Esta dosis es habitualmente letal, con rápida aparición de complicaciones y de falla multiorgánica: renal, hepática y, en especial, pulmonar. Esta última fue la condicionante de las dos muertes, a pesar de las medidas terapéuticas.

It is reported two patients who ingested a dose greater than 30 mL, which are typically lethal, with the rapid emergence of complications and multiple organ failure: kidney, liver, and especially lung, which was the condition of death, despite the therapeutic measures.

Intoxicaciones por paraquat reportadas en el Centro Toxicológico de la Región Centro Occidental "Antonio M. Pineda de Venezuela: período 1997-2000 / Paraquat intoxications reported in the Toxicological Center Antonio M. Pineda: from Venezuela 1997-2000

En Venezuela, es frecuente la utilización de plaguicidas como el paraguat en la actividad agrícola, por ello las intoxicaciones y fallecimientos que se producen anualmente por su mal uso, y manejo es importante. Se analizaron retrospectivamente los casos de intoxicaciones por paraquat registrados en el Centro Toxicológico de la Región Centro Occidental de Venezuela, durante los años 1997-2000, para evaluar frecuencia, causas, vías de ingreso y evaluación de los pacientes intoxicados. La investigación fue descriptiva, de registros médicos. Se registraron 79 pacientes; 44 pacientes del género masculino y 29 del género femenino y 6 no identificados en los registros. El promedio de edad fue de 24,22 ± 12,47 años. La principal vía de ingreso del tóxico fue oral 83.5%, y las causas de intoxicación identificadas fueron: 75,9% ocupacional y 22,8% accidental. El 49,3% de los pacientes fue dado de alta., mientras que el 8,8% falleció

In Venezuela, it is frequent the use of pesticides such as paraquat in agriculture, so poisonings and deaths that occur annually for their improper use and handling its important. We retrospectively analyzed the cases of paraquat poisoning recorded in the Poison Center of the Midwestern Region of Venezuela during the years 1997-2000, to assess prevalence, causes, access routes and evolution of poisoned patients. The research was descriptive, of medical records. There were 79 patienrs, 44 males and 29 females and 6 are not identified in the records. The average age was 24.22 ± 12.47 years. The main route of the toxic was oral 83.5%, and the causes of poisoning identified were: occupational 75.9% and accidental 22.8%. The 49.3% of patients were discharged, while 8.8% died

Down-regulation of survivin suppresses uro-plasminogen activator through transcription factor JunB

Survivin, a member of the inhibitors of apoptosis protein family, is expressed during development and in various human cancers. However, the clinical relevance of survivin in cancer is still a matter of debate. Genes induced by hepatocyte growth factor (HGF) were screened using cDNA microarray technology in the stomach cancer cell lines, NUGC3 and MKN28. The levels of JunB, survivin, and uro-plasminogen activator (uPA) were up-regulated in cells treated with HGF in a dose-dependent manner. HGF-induced up regulation of JunB, survivin, and uPA was inhibited by pre-treatment with a MEK inhibitor (PD 98059). HGF-induced up-regulation of uPA was repressed by survivin knockdown. HGF enhanced the binding activity of JunB to the survivin promoter in control cells, but not in the JunB-shRNA cells. Transfection with survivin-shRNA resulted in a decrement of cell proliferation, as determined with MTT assays. In an in vitro invasion assay, significantly fewer cells transfected with survivin shRNA than control cells were able to invade across a Matrigel membrane barrier. In conclusion, survivin appeared to play an important role in the up-regulation of uPA induced by HGF via JunB and might contribute to HGF-mediated tumor invasion and metastasis, which may serve as a promising target for gastric cancer therapy.

Intoxicación pediátrica por paraquat (gramoxone) supervivencia en dos casos / Pediatric intoxication with paraquat (gramoxone) survival of two children

El paraquat es un plaguicida agricola bipiridilo, cuyos efectos tóxicos más severos son año hepato-renal y fibrosis pulmonar irreversible. Se reportan dos casos de intoxicación en niños, por ingestión accidental de paraquat; ellos desarrollaron sialorrea, vómitos azul verdoso, lesión digestiva cáustica. dificultad respiratoria, daño hepato-renal, alteraciones radiológicas y presencia de paraquat en orina y sangre. Ambos pacientes recibieron el tratamiento disponible entre 24-48 horas despues de la ingestion y tuvieron una evolución satisfactoria. El tratamiento consistió basicamente en diálisis gastrointestinal, diuresis forzada ácida, N-acetilcisteína y dexametasona.

Paraquat is a bipyridyl agricultural pesticide, whose more severe effects are hepatic-renal damage and irreversible pulmonary fibrosis. Two children with paraquat accidental poisoning are reported; they developed syalorrhea, blue greenish vomiting, caustic digestive injury, breathing difficulty, liver and kidney damage, radiographic changes and presence of paraquat in blood and urine. Both patients received the available treatment 24-48 hours after ingetion and had a satisfactory autcome. The consisted basically of gatrointestinal dialysis, acidic forced diuresis, N-acetylcysteine and dexamethasone.

Aplicación de las normas terapéuticas en pacientes intoxicados por plaguicidas, servicio de emergencias Hospital Doctor Roberto Calderón Gutierrez, Managua 2008-2009 / Application of treatment guidelines in patients poisoned by pesticides, Hospital emergency room Doctor Roberto Calderon Gutierrez, Managua 2008-2009

El objetivo del presente estudio fue obtener información sobre la aplicacion de las Normas Terapéuticas en el manejo brindado a pacientes que acudieron por intoxicación por plaguicidas, principalmente por Fosfina, Organofosforados, Paraquat y Rodenticidas, así como información sobre las condiciones sociodemográficas de los pacientes en estudio, para responder cuál fue la distribución de frecuencia de pacientes por edad y género, la procedencia de los pacientes, grado de instrucción, así como la relación de las intoxicaciones con su evolución clínica según el manejo brindado en sala de emergencias de este centro asistencial, utilizando como base cientifica las Normas Terapeuticas del Ministerio de Salud de Nicaragua. Diseño Metodologico Tipo de Estudio: Corresponde a una investigación analítica, del cumplimiento de normas de manejo de pacientes intoxicados por plaguicidas, principalmente por Fosfina, Organofosforados, Paraquat y Rodenticidas. El Universo esta constituido por 46 pacientes correspondientes al total de ingresos con diagnóstico de intoxicación por estos plaguicidas, por el servicio de Emergencias del Hospital “Roberto Calderón Gutiérrez.” de 2008 a 2009. Resultados: Se recopilaron 46 casos de intoxicaciones por plaguicidas Fosfina, Paraquat, Organofosforados y Rodenticidas con predominio del sexo masculino, de escolaridad primaria, con una edad media entre 15 y 25 años. Geográficamente, la mayor proporción de casos corresponde a la zona urbana, sin ocupacion y solteros. El plaguicida mayor utilizado es la Fosfina, con una severidad global del 60% y una mortalidad general del 72%. La mayoria con finalidad autolítica, utilizando la vía digestiva como via de ingreso del tóxico...

Aplicación de las normas terapéuticas en pacientes intoxicados por plaguicidas, servicio de emergencias Hospital Doctor Roberto Calderón Gutierrez, Managua 2008-2009 / Application of treatment guidelines in patients poisoned by pesticides, Hospital emergency room Doctor Roberto Calderon Gutierrez, Managua 2008-2009

El objetivo del presente estudio fue obtener información sobre la aplicación de las Normas Terapéuticas en el manejo brindado a pacientes que acudieron por intoxicación por plaguicidas, principalmente por Fosfina, Organofosforados, Paraquat y Rodenticidas, así como información sobre las condiciones sociodemográficas de los pacientes en estudio, para responder cuál fue la distribución de frecuencia de pacientes por edad y género, la procedencia de los pacientes, grado de instrucción, así como la relación de las intoxicaciones con su evolución clínica según el manejo brindado en sala de emergencias de este centro asistencial, utilizando como base científica las Normas Terapeuticas del Ministerio de Salud de Nicaragua. Diseño Metodologico Tipo de Estudio: Corresponde a una investigación analítica, del cumplimiento de normas de manejo de pacientes intoxicados por plaguicidas, principalmente por Fosfina, Organofosforados, Paraquat y Rodenticidas. El Universo esta constituido por 46 pacientes correspondientes al total de ingresos con diagnóstico de intoxicación por estos plaguicidas, por el servicio de Emergencias del Hospital “Roberto Calderón Gutiérrez.” de 2008 a 2009. Resultados: Se recopilaron 46 casos de intoxicaciones por plaguicidas Fosfina, Paraquat, Organofosforados y Rodenticidas con predominio del sexo masculino, de escolaridad primaria, con una edad media entre 15 y 25 años. Geográficamente, la mayor proporción de casos corresponde a la zona urbana, sin ocupación y solteros. El plaguicida mayor utilizado es la Fosfina, con una severidad global del 60% y una mortalidad general del 72%. La mayoría con finalidad autolítica, utilizando la vía digestiva como via de ingreso del tóxico...

Suppression of ROS generation by 4,4'-diaminodiphenylsulfone in non-phagocytic human diploid fibroblasts

The action mode of 4,4'-diaminodiphenylsulfone (DDS) is still under debate, although it has long been used in treatment of several dermatologic diseases including Hansen's disease. In this study, we tested the effect of DDS as an antioxidant on paraquat-induced oxidative stress in non-phagocytic human diploid fibroblasts (HDFs). Overall, preincubation of HDFs with DDS prevented the oxidative stress and the resulting cytotoxic damages caused by paraquat in these cells. The specific effects of DDS in paraquat-treated HDFs are summarized as follows: a) reducing the expression of NADPH oxidase 4 (NOX4) by inhibiting paraquat-induced activation of PKC; b) inhibiting paraquat-induced decreases in mitochondrial complex protein levels as well as in membrane potentials; c) consequently, inhibiting the generation of cytosolic and mitochondrial superoxide anions. Taken together, these findings suggest that DDS would suppress the radical generation in non-phagocytic HDFs during oxidative stress, and that DDS might have the extended potential to be used further in prevention of other oxidative stress-related pathologies.

Tratamiento de intoxicaciones por compuestos hepatotóxicos: uso de la N-acetilcisteína y las carboximetilcisteína: [revisión] / Treatment of intoxications by hepatotoxic compounds: use of N-acetylcystein and S-carboxymetylcystein: [review]

La N-acetilcisteina (NAC) es un fármaco con propiedades antidóticas útiles en la intoxicación por compuestos hepatotóxicos, como paraquat, acetaminofen y fósforo inorgánico. No se encuentra fácilmente disponible en Venezuela a pesar que la frecuencia y severidad de este tipo de intoxicación son significativas. Se discuten ciertas características fármacocinéticas y fármacodinámicas de la NAC y de la S-carboximetilcisteina (SCMC), presente en el mercado farmacéutico venezolano. Además se presenta una revisión de las experiencias clínicas y experimentales con la SCMC en intoxicaciones por compuestos hepatototóxicos.

N-acetylcysteine (NAC) is a drug with antidotal properties useful in poisoning by hepatotoxic compounds such as paraquat, acetaminophen and inorganic phosphorus. Although the frequency and severity of this type of poisoning are significant, NAC is not readily available in Venezuela. Certain pharmacokinetic and pharmacodynamic characteristics of NAC and S-carboxymetylcisteine (SCMC), available in venezuelan pharmaceutical market are discussed. In addition, a review of the clinical and experimental experiences with SCMC in poisoning for hepatotoxic compounds is presented.

Clinical Outcome of Paraquat Poisoning

No abstract available.

Marked Recovery From Paraquat-Induced Lung Injury During Long-Term Follow-up

BACKGROUND/AIMS: Paraquat-induced lung injury has been considered a progressive and irreversible disease. The purpose of this study was to report the long-term evolution of lung lesions in eight survivors with significant paraquat-induced lung injuries who could be followed-up for longer than 6 months. METHODS: We retrospectively examined high-resolution computed tomography and pulmonary function test of eight survivors with significant paraquat-induced lung injurys. RESULTS: High-resolution computed tomography revealed a predominant pattern of irregularly shaped consolidation with traction bronchiectasis at 1-2 months after paraquat poisoning, a mixed pattern of irregularly shaped consolidation and ground-glass opacity at 3-12 months, and a mixed pattern of consolidation, groundglass opacity, and honeycombing at 1-2 years. At 3-12 months after paraquat ingestion, the areas of consolidation had markedly decreased and the decreased lung volume had returned to normal. At 1-2 years after paraquat poisoning, the cystic changes had disappeared. At 2-3 years after paraquat poisoning, the decrease in forced vital capacity had greatly improved to the normal range. CONCLUSIONS: Recovery of nearly normal pulmonary structure and function may occur over several years following paraquat poisoning. Pulmonary function (both forced vital capacity and forced expiratory volume in 1 sec) evolved toward normal in the long-term survivors of paraquat poisoning with initial prominent lung injuries.

Determinación de paraquat en orina utilizando un sistema de inyección en flujo continuo / Determination of paraquat in urine samples by flow-injection analysis

El paraguat es un herbicida que pertenece al grupo de los biperidilos. Su determinación cuantitativa en orina es muy importante para diagnosticar la supervivencia de pacientes intoxicados. Muchos centros hospitalarios utilizan pruebas semicuantitativas para la determinación de paraquat en muestras biológicas. Sin embargo, éstas suelen carecer de precisión y exactitud. Por tanto, el desarrollo de métodos alternativos simples, exactos, precisos y accesibles podría resultar muy útil en instituciones hospitalarias. Sobre la base de estas consideraciones, se propone un método de análisis por inyección en flujo y detección espectrofotométrica para la determinación cuantitativa de paraquat en muestras de orina. La determinación se basa en la formación de un producto coloreado (600 nm) posterior a la reducción de paraquat con glucosa en un medio alcalino, mediante un sistema en línea. Bajo las condiciones óptimas de operación, la ley de Beer se cumple en el intervalo 1-50 µg mL-1 de paraquat con un coeficiente de correlación >0,999. La frecuencia de análisis fue de 12 h-1 con una desviación estándar relativa del 2,8% para una solución muestra que contiene 10 µg mL-1 de paraquat (n=3). El estudio de recuperación osciló entre 97,9 y 102,1%. El método analítico fue aplicado satisfactoriamente al análisis de muestras de dos pacientes intoxicados con paraquat.

Paraguat is a herbicide beloging to the bipyridinium group.The quantitative determination of paraquat in urine of humans is very important to diagnose survival of intoxicated patients. Many hospitals use semi-quantitative tests for determining paraquat in biological samples. However, they often lack precision and accuracy. Therefore, the development of simple, precise, accurate and accessible alternative methods could be very useful in hospital institutions. Based on these considerations, a flow-injection spectrophotometric procedure is proposed for paraquat determination in urine samples. The determination is based on the formation of a coloured product (600 nm) after on-line reduction of paraquat with glucose in alkaline medium. Under optimal conditions of operation, Beer's law is obeyed in a concentration range of 1-50 µg mL-1 of paraquat with a correlation coefficient >0.999. The analytical frequency was 12 h-1 and the relative standard deviation was 2.8% for a sample solution containing 10 µg mL-1 paraquat (n=3). Recovery studies were between 97.9 and 102.1%. The analytical method was satisfactorily applied in the analyses of samples from two intoxicated patients.

Effects of paraquat on anti-oxidant system in rats.

The toxic effects of paraquat on the anti-oxidant defense system of male albino rats were evaluated, after administering either a single dose (1.5 and 7.5 mg/kg of body weight) or continuous daily doses (same as above, i.e., 1.5 mg/kg and 7.5 mg/kg of body weight) for 3 and 7 days. Glutathione levels in blood cells, liver, lung and kidney tissues decreased in a dose and time dependent manner. Glutathione reductase and glucose-6-phosphate dehydrogenase activity decreased, whereas the activity of glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase increased in paraquat exposure. Malondialdehyde formation also increased in a dose and time dependent manner. The alterations of anti-oxidant system particularly glutathione can be utilized as biomarkers during management of paraquat poisoning.