RESUMEN
Acute lung injury is an inflammation that triggers acute respiratory distress syndrome with perialveolar neutrophil infiltration, alveolar-capillary barrier damage, and lung edema. Activation of the toll-like receptor 4 complex (TLR4/MD2) and its downstream signaling pathways are responsible for the cytokine storm and cause alveolar damage. Due to the complexity of this pulmonary inflammation, a defined pharmacotherapy has not been established. Thus, this study evaluated the anti-inflammatory potential of milonine, an alkaloid of Cissampelos sympodialis Eichl, in an experimental model of lung inflammation. BALB/c mice were lipopolysaccharide-challenged and treated with milonine at 2.0 mg/kg. Twenty-four hours later, the bronchoalveolar fluid, peripheral blood, and lungs were collected for cellular and molecular analysis. The milonine treatment decreased the cell migration (mainly neutrophils) to the alveoli, the pulmonary edema, and the cytokine levels (IL-1ß, IL-6, TNF-α). The systemic IL-6 level was also reduced. The milonine docking analysis demonstrated hydrophobic interaction at TLR4/MD2 groove with Ile124 and Phe126 amino acids. Indeed, the alkaloid downregulated the kinase-Akt and NF-κB through TLR4/MD2. Therefore, milonine is an effective inflammatory modulator being a potential molecule for the treatment of lung inflammation.
Asunto(s)
Lesión Pulmonar Aguda , Edema Pulmonar , Ratones , Animales , FN-kappa B , Lipopolisacáridos , Receptor Toll-Like 4 , Proteínas Proto-Oncogénicas c-akt , Interleucina-6 , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Edema Pulmonar/inducido químicamente , Edema Pulmonar/tratamiento farmacológico , Transducción de SeñalRESUMEN
Cytarabine is effectively used in the treatment of adult acute leukemia, but it has a dose-limiting side effect of fatal pulmonary oedema because it increases the vascular permeability of the alveolar capillaries. The aim of the present study was to conduct a radiological, biochemical and histopathological investigation of the effect of rutin on cytarabine-associated pulmonary oedema in rats. Rats were treated with a combination of rutin+cytarabine by administering oral rutin at a dose of 50 mg/kg; other rat groups were orally administered the same volume of physiological saline. One hour after administration of rutin or saline, the rutin+cytarabine and cytarabine groups received an intraperitoneal injection of cytarabine (200 mg/kg). This administration procedure was repeated once a day for 14 days. Radiologically, 50% of the animals given cytarabine alone showed lung oedema, but the rutin+cytarabine group showed no oedema. The inclusion of rutin decreased the amounts of cytarabine-associated malondialdehyde, tumour necrosis factor-α, and nuclear factor-κB in the lung tissue. Rutin also inhibited the reduction of total glutathione by nitric oxide. These findings suggest that rutin may be a beneficial adjunct that can minimise the development of cytarabine-associated pulmonary oedema.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Citarabina/efectos adversos , Edema Pulmonar/tratamiento farmacológico , Rutina/uso terapéutico , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Masculino , FN-kappa B/análisis , Oxidantes/sangre , Estrés Oxidativo/efectos de los fármacos , Edema Pulmonar/inducido químicamente , Edema Pulmonar/patología , Ratas , Ratas Wistar , Rutina/farmacología , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Obese patients are at higher risk of developing acute respiratory distress syndrome (ARDS); however, their survival rates are also higher compared to those of similarly ill non-obese patients. We hypothesized that obesity would not only prevent lung inflammation, but also reduce remodeling in moderate endotoxin-induced acute lung injury (ALI). Obesity was induced by early postnatal overfeeding in Wistar rats in which the litter size was reduced to 3 pups/litter (Obese, n = 18); Control animals (n = 18) were obtained from unculled litters. On postnatal day 150, Control, and Obese animals randomly received E. coli lipopolysaccharide (ALI) or saline (SAL) intratracheally. After 24 h, echocardiography, lung function and morphometry, and biological markers in lung tissue were evaluated. Additionally, mediator expression in neutrophils and macrophages obtained from blood and bronchoalveolar lavage fluid (BALF) was analyzed. Compared to Control-SAL animals, Control-ALI rats showed no changes in echocardiographic parameters, increased lung elastance and resistance, higher monocyte phagocytic capacity, collagen fiber content, myeloperoxidase (MPO) activity, and levels of interleukin (IL-6), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, and type III (PCIII), and I (PCI) procollagen in lung tissue, as well as increased expressions of TNF-α and monocyte chemoattractant protein (MCP)-1 in blood and BALF neutrophils. Monocyte (blood) and macrophage (adipose tissue) phagocytic capacities were lower in Obese-ALI compared to Control-ALI animals, and Obese animals exhibited reduced neutrophil migration compared to Control. Obese-ALI animals, compared to Obese-SAL, exhibited increased interventricular septum thickness (p = 0.003) and posterior wall thickness (p = 0.003) and decreased pulmonary acceleration time to pulmonary ejection time ratio (p = 0.005); no changes in lung mechanics, IL-6, TNF-α, TGF-ß, PCIII, and PCI in lung tissue; increased IL-10 levels in lung homogenate (p = 0.007); reduced MCP-1 expression in blood neutrophils (p = 0.009); decreased TNF-α expression in blood (p = 0.02) and BALF (p = 0.008) neutrophils; and increased IL-10 expression in monocytes (p = 0.004). In conclusion, after endotoxin challenge, obese rats showed less deterioration of lung function, secondary to anti-inflammatory and anti-fibrotic effects, as well as changes in neutrophil and monocyte/macrophage phenotype in blood and BALF compared to Control rats.
Asunto(s)
Lesión Pulmonar Aguda/fisiopatología , Obesidad/fisiopatología , Neumonía/fisiopatología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/etiología , Animales , Líquido del Lavado Bronquioalveolar , Quimiotaxis de Leucocito , Colágeno/metabolismo , Citocinas/biosíntesis , Citocinas/genética , Femenino , Fibrosis , Regulación de la Expresión Génica , Tabiques Cardíacos/patología , Lipopolisacáridos/toxicidad , Pulmón/patología , Pulmón/fisiopatología , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Neutrófilos/inmunología , Neutrófilos/metabolismo , Obesidad/complicaciones , Hipernutrición/complicaciones , Peroxidasa/análisis , Fagocitosis , Neumonía/inducido químicamente , Edema Pulmonar/inducido químicamente , Edema Pulmonar/fisiopatología , Ratas , Ratas WistarRESUMEN
Las tiazidas son fármacos frecuentemente usados en la terapia de la hipertensión arterial. Las reacciones adversas de riesgo vital como shock y edema pulmonar agudo son raros. Comunicamos el caso de una mujer de 55 años de edad atendida en Hospital de Puerto Montt, quien tras dos horas de ingerir hidroclorotiazida presentó disnea. Los exámenes de laboratorio generales e imágenes muestran cuadro concordante con edema pulmonar agudo no cardiogénico. Además de la suspensión del fármaco, se realizó soporte hemodinámico y ventilatorio no invasivo, evidenciándose resolución del cuadro a las 48 h. La paciente fue dada de alta 3 días después de su ingreso sin sintomatología.
Thiazides are drugs often used in management of high arterial blood pressure. Shock and acute pulmonary edema are rarely described as adverse reactions related to this drug. We report the case of a 55 years-old woman admitted at Hospital de Puerto Montt, Chile. Two hours after having her first dose of hydrochlorothiazide she presented dyspnea. Laboratory tests and images support the diagnosis of non-cardiogenic pulmonary edema. Resolution of her clinical picture was observed 48 hours after hydrochlorothiazide administration was discontinued and hemodynamic and non invasive ventilation support were supplied. The patient was discharged without symptoms, 3 days after entering to hospital.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Edema Pulmonar/inducido químicamente , Hidroclorotiazida/efectos adversos , Antihipertensivos/efectos adversos , Edema Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Tiazidas/efectos adversosRESUMEN
The epidemiological, clinical and pathological aspects of a spontaneous outbreak of Palicourea aeneofusca poisoning in goats are reported. The main clinical signs were motor incoordination, generalized muscle tremors, broad-based posture, tachypnea, tachycardia, vocalization and respiratory distress. Two goats died 5 and 20 min after the observation of the first clinical signs. Another that was found recumbent died 80 h later. One goat with mild clinical signs recovered. Congestion and hemorrhages were observed macroscopically and histologically in most organs. Pulmonary edema was also observed. The main microscopic findings consisted of cytoplasmic vacuolization and necrosis of the renal tubular epithelium. The average concentration of monofluoroacetate obtained in sixteen samples of P. aeneofusca was 0.29 ± 0.17%. It is concluded that P. aeneofusca is toxic to goats under natural conditions.
Asunto(s)
Enfermedades de las Cabras/inducido químicamente , Insuficiencia Cardíaca/veterinaria , Intoxicación por Plantas/veterinaria , Rubiaceae/química , Rubiaceae/envenenamiento , Animales , Brasil/epidemiología , Fluoroacetatos/análisis , Enfermedades de las Cabras/mortalidad , Cabras , Insuficiencia Cardíaca/inducido químicamente , Túbulos Renales/patología , Intoxicación por Plantas/mortalidad , Edema Pulmonar/inducido químicamenteRESUMEN
In Chile, hydrochlorothiazide is frequently prescribed as first line antihypertensive therapy. Among it’s well known adverse reactions are: electrolytic disorders, hyperuricemia, dyslipidemia, agranulocytosis and azotemia. Acute pulmonary edema is a rare and potentially lethal adverse effect. Only 50 cases have been reported since 1968. In this article, we discuss a case of a 70 year old woman who, one hour after the ingestion of hydrochlorotiazide, presented acute and progressive dyspnea. Her clinical and radiologic findings are compatible with non-cardiogenic acute pulmonary edema.
En Chile, la hidroclorotiazida se utiliza ampliamente como terapia de primera línea en la hipertensión arterial esencial. Entre los efectos adversos más conocidos destacan: trastornos hidroelectrolíticos, hiperuricemia, dislipidemia, azotemia, entre otros. El edema pulmonar agudo es un efecto adverso infrecuente y potencialmente grave. Desde 1968, se han reportado 50 casos clínicos en la literatura. En este artículo presentamos el caso clínico de una mujer de 70 años atendida en el Hospital Santiago Oriente quien, una hora posterior a la ingesta de hidroclorotiazida, presenta disnea aguda progresiva. El estudio clínico y radiológico es compatible con edema pulmonar agudo no cardiogénico.
Asunto(s)
Humanos , Femenino , Anciano , Edema Pulmonar/inducido químicamente , Diuréticos/efectos adversos , Hidroclorotiazida/efectos adversos , Edema Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Enfermedad Aguda , Inhibidores de los Simportadores del Cloruro de Sodio/efectos adversos , Unidades de Cuidados IntensivosRESUMEN
Acute respiratory distress syndrome (ARDS) is the most severe lung inflammatory manifestation and has no effective therapy nowadays. Sepsis is one of the main illnesses among ARDS causes. The use of fluid resuscitation is an important treatment for sepsis, but positive fluid balance may induce pulmonary injury. As an alternative, fluid resuscitation with hypertonic saline ((HS) NaCl 7.5%) has been described as a promising therapeutical agent in sepsis-induced ARDS by the diminished amount of fluid necessary. Thus, we evaluated the effect of hypertonic saline in the treatment of LPS-induced ARDS. We found that hypertonic saline (NaCl 7.5%) treatment in rat model of LPS-induced ARDS avoided pulmonary function worsening and inhibited type I collagen deposition. In addition, hypertonic saline prevented pulmonary injury by decreasing metalloproteinase 9 (MMP-9) activity in tissue. Focal adhesion kinase (FAK) activation was reduced in HS group as well as neutrophil infiltration, NOS2 expression and NO content. Our study shows that fluid resuscitation with hypertonic saline decreases the progression of LPS-induced ARDS due to inhibition of pulmonary remodeling that is observed when regular saline is used.
Asunto(s)
Lesión Pulmonar Aguda/prevención & control , Remodelación de las Vías Aéreas (Respiratorias) , Fluidoterapia/métodos , Lipopolisacáridos , Pulmón , Síndrome de Dificultad Respiratoria/terapia , Solución Salina Hipertónica/administración & dosificación , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/fisiopatología , Resistencia de las Vías Respiratorias , Animales , Colágeno Tipo I/metabolismo , Modelos Animales de Enfermedad , Quinasa 1 de Adhesión Focal/metabolismo , Pulmón/metabolismo , Pulmón/patología , Pulmón/fisiopatología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Infiltración Neutrófila , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Edema Pulmonar/inducido químicamente , Edema Pulmonar/prevención & control , Ratas Wistar , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/metabolismo , Síndrome de Dificultad Respiratoria/fisiopatología , Factores de TiempoRESUMEN
Se presenta el caso clínico de una paciente que instaló edema pulmonar no cardiogénico, luego de la inyección intravenosa de eugenol requiriendo un tratamiento agresivo de soporte de las funciones vitales en una Unidad de Cuidados Intensivos.
It is presented the case of a patient, who developed a non-cardiogenic pulmonary edema, after the intravenous administration of eugenol, requiring aggressive supportive measures in an Intensive Care Unit.
Asunto(s)
Humanos , Femenino , Adulto , Eugenol/toxicidad , Edema Pulmonar/inducido químicamente , Automedicación/efectos adversosRESUMEN
The scorpion Tityus serrulatus is responsible for the most severe accidents that have been registered in Brazil, mainly in the state of Minas Gerais (MG), being the lung edema (LE), the main cause of death in these accidents. Although an increased in the number of accidents caused to this species in Federal District (Distrito Federal - DF), it seems that this particular species is not responsible for severe scorpionism cases in this region. Given this observation, we tested the toxicity in mice and compared the ability of T. serrulatus venom from DF (Ts-DF) and Minas Gerais State (Ts-MG) to induce LE in rats. The LD50 of Ts-DF venom was 51.6 µg/mouse, almost twice (1.98) higher than that obtained for Ts-MG venom. The ability of venom (0.5 mg/kg) to induce LE in rats was determined by the wet weight differences between treated and untreated lungs, by pulmonary morphological analyses and by pulmonary vascular permeability (PVP) using the Evans blue protocol. Significant differences in the wet weight of lungs and changes in PVP were found in Ts-MG venom treated rats when compared to rats treated with Ts-DF venom or untreated rats (p < 0.001), but no differences occurred when comparing rats treated with Ts-DF venom and untreated rats (p < 0.05). These results were confirmed by evaluation of pulmonary morphology. Comparison of chromatographic profiles obtained from these venoms (Ts-DF and Ts-MG) using the fractal dimension (D) analysis and the molecular mass fingerprint of the chromatographic fractions showed a higher number of components between 35 and 40% acetonitrile in Ts-MG venom than in Ts-DF venom, indicating a higher diversity of sodium channel modulators in that venom.
Asunto(s)
Discinesia Inducida por Medicamentos/patología , Variación Genética , Edema Pulmonar/inducido químicamente , Venenos de Escorpión/toxicidad , Escorpiones/química , Análisis de Varianza , Animales , Brasil , Permeabilidad Capilar/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Disnea/inducido químicamente , Azul de Evans , Fractales , Geografía , Dosificación Letal Mediana , Recuento de Leucocitos , Masculino , Ratones , Edema Pulmonar/patología , Ratas , Ratas Wistar , Venenos de Escorpión/genética , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
La intoxicación por salicilatos frecuentemente no es tenida en cuenta como causa de edema pulmonar no cardiogénico y de alteración del sensorio en pacientes adultos. Se describe el caso de una mujer de 52 años de edad, la cual presentó dos episodios de edema pulmonar no cardiogénico habiendo requerido para su manejo, asistencia ventilatoria mecánica. La presentación clínica de la intoxicación fue reconocida al ingreso al servicio de urgencias y llevó al diagnóstico correcto. Se le realizó hemodiálisis y alcalinización urinaria llevando a una rápida resolución del edema pulmonar. Varios aspectos de la presentación clínica sugirieron que la paciente tenía una intoxicación crónica, una condición que a menudo no es diagnosticada oportunamente, lo que contribuye al aumento de la morbi-mortalidad en estos pacientes. Frente a un caso de edema pulmonar agudo no cardiogénico debe considerarse la posibilidad de intoxicación con salicilatos, porque la institución rápida de una terapia apropiada, incluyendo la hemodiálisis, una vez establecido el diagnóstico, es un factor determinante de los resultados en esta grave intoxicación.
Salicylate intoxication is frequently overlooked as a cause of noncardiogenic pulmonary edema and altered mental status in adult patients. We described the case of a 52 years-old woman who presented two episodes of recurrent non-cardiogenic pulmonary edema requiring intubation. On admission, recognition of the clinical syndrome in the emergency department led to the correct diagnosis of salicylate intoxication. The patient was successfully treated with hemodialysis and urinary alkalinization, leading to rapid resolution of pulmonary edema and extubation. Several aspects of the clinical presentation suggest that the patient suffered from chronic salicylism, a condition often misdiagnosed or diagnosed late in the course of disease, contributing to substantial morbidity and mortality in these patients. This poisoning should be considered in the differential diagnosis of acute pulmonary edema not cardiogenic and altered sensorium because rapid institution of appropriate therapy, including hemodialysis, once the diagnosis is established is an important determinant of outcome in this serious disorder.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Aspirina/envenenamiento , Pruebas de Toxicidad Crónica , Edema Pulmonar/inducido químicamente , Edema Pulmonar/terapia , Edema Pulmonar/diagnóstico , Edema Pulmonar/tratamiento farmacológicoRESUMEN
The scorpion envenomation is considered the second event by poisonous animals in importance around the world according to the World Health Organization. In Colombia there are 35 species of clinical significance, among them, the genus Tityus, which contains the most deadly scorpions in South America and is represented by 29 species of wide distribution in Colombia, which include Tityus pachyurus causing life-threatening events, especially in children. The present work shows the case of a 12 years old boy, from Tolemaida to 2 h of Bogotá D.C., who was stung by a scorpion on his right thigh, with the onset of intense signs and symptoms of local effect rapidly progressing to severe systemic involvement causing myocardial dysfunction, cardiovascular collapse and heart arrest, and his favorable response to adequate basic and advanced life support and use of scorpion-specific F(ab')2 antivenom.
Asunto(s)
Antivenenos/uso terapéutico , Paro Cardíaco/inducido químicamente , Edema Pulmonar/inducido químicamente , Picaduras de Escorpión/inducido químicamente , Venenos de Escorpión/envenenamiento , Taquicardia Ventricular/inducido químicamente , Animales , Niño , Dopamina/uso terapéutico , Quimioterapia Combinada , Paro Cardíaco/tratamiento farmacológico , Paro Cardíaco/fisiopatología , Humanos , Masculino , Nitroprusiato/uso terapéutico , Prazosina/uso terapéutico , Edema Pulmonar/tratamiento farmacológico , Edema Pulmonar/fisiopatología , Picaduras de Escorpión/tratamiento farmacológico , Escorpiones/fisiología , Taquicardia Ventricular/fisiopatología , Resultado del TratamientoRESUMEN
The association of pulmonary hypertensive vascular disease with nonketotic hyperglycinemia is rare. We describe 5 infants diagnosed with nonketotic hyperglycinemia, in whom pulmonary hypertensive vascular disease was the main presenting feature, and who developed severe pulmonary edema in response to pulmonary vasodilators.
Asunto(s)
Hiperglicinemia no Cetósica/diagnóstico , Hipertensión Pulmonar/etiología , Edema Pulmonar/inducido químicamente , Vasodilatadores/efectos adversos , Femenino , Humanos , Hiperglicinemia no Cetósica/complicaciones , Hiperglicinemia no Cetósica/mortalidad , Hiperglicinemia no Cetósica/fisiopatología , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/fisiopatología , Lactante , Pulmón/patología , Masculino , Edema Pulmonar/diagnóstico por imagen , Edema Pulmonar/mortalidad , Radiografía , Insuficiencia Respiratoria/etiología , Estudios RetrospectivosRESUMEN
This study investigated the effect of the bark extract of Bathysa cuspidata on paraquat (PQ)-induced extra-pulmonary acute lung injury (ALI) and mortality in rats. ALI was induced with a single dose of PQ (30 mg/kg, i.p.), and animals were treated with B. cuspidata extract (200 and 400 mg/kg). Analyses were conducted of survival, cell migration, lung oedema, malondialdehyde, proteins carbonyls, catalase, superoxide dismutase, histopathology and the stereology of lung tissue. Rats exposed to PQ and treated with 200 and 400 mg of the extract presented lower mortality (20% and 30%), compared with PQ alone group (50%). Furthermore, lung oedema, septal thickening, alveolar collapse, haemorrhage, cell migration, malondialdehyde and proteins carbonyl levels decreased, and catalase and superoxide dismutase activity were maintained. These results show that the bark extract of B. cuspidata reduced PQ-induced extra-pulmonary ALI and mortality in rats and suggest that these effects may be associated with the inhibition of oxidative damage.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Herbicidas/toxicidad , Paraquat/toxicidad , Extractos Vegetales/uso terapéutico , Edema Pulmonar/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/mortalidad , Animales , Catalasa/metabolismo , Movimiento Celular/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Malondialdehído/metabolismo , Extractos Vegetales/farmacología , Edema Pulmonar/inducido químicamente , Edema Pulmonar/metabolismo , Edema Pulmonar/mortalidad , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
The aim of this study was to determine the cause of sudden deaths in sheep in the Anari Valley of the state of Rondônia, in northern Brazil. In one outbreak, sheep were placed in an area where the owner had cut Amorimia (Mascagnia) sepium and let it dry for two days. Fourteen out of 35 sheep died with few outward clinical signs observed over a period of about 10 h after the ingestion of the dry plant. Dry A. sepium was administered experimentally to 9 sheep. Five died after the ingestion of single doses of 3-6.6 g/kg body weight (bw). Two sheep died after the ingestion of total doses of 6.4-31 g/kg bw over the course of 4 and 5 days, respectively, and one died after being treated with 33 daily doses of 0.56 g/kg bw. Six sheep died during exercise, and three died without exercise. Clinical signs were anorexia, muscular tremors, dyspnea, jugular engorgement, tachycardia, apathy, opisthotonos, foam in the nose, and recumbency. One sheep, which ingested a single dose of 1 g/kg bw, was not affected. The main macroscopic lesion was pulmonary edema. Histologic examination of the heart revealed degeneration and necrosis of cardiomyocytes, as well as multifocal inflammatory infiltrate of mononuclear cells. Fibrosis, neovascularization and infiltration by mononuclear inflammatory cells were observed in the sheep that ingested the plant for 33 days. Vacuolar-hydropic degeneration was observed in the epithelial cells of renal tubules of four sheep. It is concluded that A. sepium is responsible for sudden deaths in sheep.
Asunto(s)
Brotes de Enfermedades/veterinaria , Malpighiaceae/toxicidad , Intoxicación por Plantas/veterinaria , Edema Pulmonar/veterinaria , Enfermedades de las Ovejas/inducido químicamente , Enfermedades de las Ovejas/epidemiología , Animales , Brasil/epidemiología , Riñón/patología , Malpighiaceae/química , Miocardio/patología , Intoxicación por Plantas/epidemiología , Intoxicación por Plantas/patología , Edema Pulmonar/inducido químicamente , Edema Pulmonar/epidemiología , Edema Pulmonar/patología , Ovinos , Enfermedades de las Ovejas/patologíaRESUMEN
We reported the case of an adolescent, without neurological background, who attempted suicide by organochlorine pesticide ingestion. The acute intoxication was expressed as a convulsive status epilepticus followed by an acute neurogenic pulmonary edema with rapid recovery within 48 hours. The diagnosis of neurogenic pulmonary edema in pediatrics, and particulary after a seizure, is unusual and often an exclusion one. Its evolution tends to be favorable, but can be fatal if it is not recognized and treated early. An acute nervous system injury associated with signs and symptoms of respiratory failure suggests the diagnosis. Other causes of pulmonary edema must be ruled out in order to avoid evaluation and treatment mistakes.
Asunto(s)
Hidrocarburos Clorados/envenenamiento , Plaguicidas/envenenamiento , Edema Pulmonar/inducido químicamente , Intento de Suicidio , Adolescente , Femenino , Humanos , Enfermedades del Sistema Nervioso/inducido químicamenteRESUMEN
The scorpion-envenoming syndrome has an incidence of approximately 8000 accidents/year in Brazil; with most severe cases occurring during childhood and elderly. Previous results from our laboratory suggest that the effects of scorpion toxins on the central nervous system play a major role on the lethality induced by scorpion envenoming. Our group has shown that the pre-treatment with carbamazepine (CBZ) is able to increase the latency-to-death in developing animals inoculated with tityustoxin, a toxic fraction of the Tityus serrulatus crude venom. Nevertheless, in order to perceive CBZ as potentially useful in clinical practice, the efficiency of CBZ against crude venom inoculation and the pharmacological treatment introduced after envenomation must be addressed. Thus, the objective of this work was to evaluate CBZ therapeutic efficiency against scorpion envenomation in developing rats. Animals were treated with i.p. injections of either vehicle or CBZ (50 mg/kg or 100 mg/kg) 10 min after injected with a s.c. fixed volume of either saline or crude T. serrulatus venom extract (48 mg/kg). The dose chosen for venom inoculation was 16 times its DL50 for 21-day-old Wistar rats, invariably inducing death within 2 h. Although CBZ did not significantly reduce the pulmonary edema, it was effective in increasing survival rate by approximately 75% in treated rats. In conclusion, CBZ was effective in the treatment of T. serrulatus envenomation even though not blocking the pulmonary edema.
Asunto(s)
Antivenenos/farmacología , Carbamazepina/farmacología , Venenos de Escorpión/toxicidad , Análisis de Varianza , Animales , Antivenenos/administración & dosificación , Carbamazepina/administración & dosificación , Relación Dosis-Respuesta a Droga , Estimación de Kaplan-Meier , Masculino , Edema Pulmonar/inducido químicamente , Edema Pulmonar/tratamiento farmacológico , Distribución Aleatoria , Ratas , Ratas Wistar , Factores de Tiempo , Resultado del TratamientoRESUMEN
The scorpion envenoming syndrome is a serious public health matter in Brazil. The most severe cases occur during childhood and elderly. Previous results from our laboratory suggest that the effects of scorpion toxins on the central nervous system play a major role on the lethality induced by scorpion envenoming. The aim of this work is to evaluate the therapeutic potential of carbamazepine (CBZ) injected i.p. 90 min before s.c. tityustoxin (TsTX) injection in weanling rats. Rats were divided into six experimental groups according to s.c. injection (saline or TsTX) and i.p. treatment (vehicle or CBZ 12, 50 and 100 mg/kg): Sal/Veh group (n=4); Sal/CBZ100 (n=4); TsTX/CBZ12 (n=6); TsTX/CBZ50 (n=8); TsTX/CBZ100 (n=8) and, at last, TsTX/Veh (n=8). The dose of TsTX was the same for all groups: 6.0mg/kg, twice the DL50 for weanling rats. Video images were recorded until death or for a maximum period of 240 min. Lungs were excised and weighed to evaluate edema. The results showed that CBZ (12, 50 and 100mg/kg) was able to increase the survival rate and latency-to-death of the rats. Only the group treated with 100mg/kg of CBZ had a decrease in the pulmonary edema. The known effect of CBZ reducing neuronal excitability most likely protected the neural substrates targeted by TsTX. Although treatment was performed before TsTX inoculation, the results are promising regarding CBZ as a therapeutic coadjuvant in the treatment of scorpion poisoning. The pharmacokinetics of CBZ can be very much improved by either changing the form of administration or encapsulating the drug in order to enhance solubility.
Asunto(s)
Carbamazepina/uso terapéutico , Sistema Nervioso Central/efectos de los fármacos , Venenos de Escorpión/antagonistas & inhibidores , Canales de Sodio/efectos de los fármacos , Factores de Edad , Animales , Animales Recién Nacidos , Anticonvulsivantes/uso terapéutico , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/fisiopatología , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/fisiopatología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Interacciones Farmacológicas/fisiología , Femenino , Pulmón/inervación , Pulmón/fisiopatología , Neurotoxinas/antagonistas & inhibidores , Neurotoxinas/toxicidad , Edema Pulmonar/inducido químicamente , Edema Pulmonar/tratamiento farmacológico , Edema Pulmonar/fisiopatología , Ratas , Ratas Wistar , Venenos de Escorpión/toxicidad , Bloqueadores de los Canales de Sodio/antagonistas & inhibidores , Bloqueadores de los Canales de Sodio/toxicidad , Canales de Sodio/metabolismo , Factores de Tiempo , Resultado del Tratamiento , DesteteRESUMEN
The scorpion envenoming syndrome is a serious public health matter in Brazil. Previous results from our laboratory suggest that the effects of scorpion toxins on the central nervous system play a major role on the lethality induced by scorpion envenoming. The objective of this work is to evaluate carbamazepine (CBZ) as a potential therapeutic agent against tityustoxin (TsTX) envenomation. The choice of i.c.v. toxin injection assures that TsTX is readily available in the parenchyma, configuring a worst case scenario for protecting the CNS afflicted by envenomation. Adult Wistar rats were submitted to surgery for guide cannulae (lateral ventricle) and electrodes (EEG-parietal cortices and ECG-thoracic leads) implantation. Animals (n=25) were treated with i.p. injections of either vehicle or CBZ 90 min before injected i.c.v. with a fixed volume of either saline or TsTX: vehicle treated/TsTX injected (1.74 microg, i.c.v.; n=4), CBZ treated (50mg/kg, i.p.)/TsTX injected (n=12); CBZ treated/saline injected (n=5); and vehicle treated/saline injected (n=4). Video EEG/ECG was recorded until death or for a maximum period of 90 min. Lungs were excised and weighed to evaluate edema. The results showed that 10 out of 12 CBZ treated rats survived to TsTX i.c.v. microinjection. CBZ significantly decreased cardiac arrhythmias and pulmonary edema in rats injected with TsTX. Furthermore, CBZ also significantly increased the latency for the first cortical epileptiform discharge. The known effect of CBZ reducing neuronal excitability most likely protected the neural substrates targeted by TsTX. CBZ was efficient in attenuating envenoming symptoms after the i.c.v. inoculation of the TsTX in rats. Thus, CBZ can be proposed as a therapeutic coadjuvant in the treatment of scorpion poisoning.
Asunto(s)
Carbamazepina/farmacología , Sistema Nervioso Central/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Neurotoxinas/toxicidad , Venenos de Escorpión/toxicidad , Análisis de Varianza , Animales , Sistema Nervioso Central/fisiología , Vías de Administración de Medicamentos , Interacciones Farmacológicas , Electrocardiografía/métodos , Electroencefalografía/métodos , Masculino , Microinyecciones/métodos , Edema Pulmonar/inducido químicamente , Edema Pulmonar/prevención & control , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacosRESUMEN
The 99 lethal dose in an acute toxicity study of two anticancer novel molecules named casiopeinas((R)) in dogs was calculated to be 200 mg/m(2) for casiopeina III-ia and 160 mg/m(2) for casiopeina IIgly. Considering therapeutic dose ranges from 3.6 to 18 mg/m(2) for the former and 1.2 to 3 mg/m(2) for the latter, true therapeutic margin of safety varies from 4.7 to 23.6 mg/m(2) and from 20 to 50 mg/m(2), respectively. For both casiopeinas intravenous administration of the corresponding lethal dose in 100 ml of 5% dextrose solution in a time period of 30 min. induced death after an almost uneventful latency time period of 30-50 min. Then, after an apparently sudden onset, changes in blood gases indicated respiratory distress (PO(2) from 82.5% to 26.5% for casiopeina III-ia and from 88.6% to 37.5% for casiopeina IIgly; end-tidal CO(2) from 38 to 8.1 mmHg for the first and from 35.1 to 11.2 mmHg for the second, this was almost simultaneously confirmed by the onset of tachypnoea (from 16 to almost 60 breaths/min. for both casiopeinas) and by a drop in arterial blood pressure (from 117 to 51 mmHg for casiopeina III-ia and from 108 to 49 mmHg for casiopeina IIgly). Reflex tachycardia occurs at the beginning of intravenous administration followed by bradycardia a few minutes later (from 158 to 63 beats/min. for casiopeina III-ia and from 148 to 56 beats/min. for casiopeina IIgly). Finally, cardiac arrest occurred no later than 25 min. towards the end of these events lung oedema appeared as fluid dripping from the endotracheal tube. Death occurred in a mean of 15 +/- 5 min. S.D. from the beginning of the end of the latency period. For both casiopeina's data allow the speculation that lung oedema is caused by a joined toxicity to the lung capillary bed, and particularly to the heart. Carvedilol premedication for 8 days delayed the outcome of lung oedema by approximately 8 hr but could not prevent it.