RESUMEN
RATIONALE: The purpose of this study was to identify the chemical responsible for cholestatic hepatitis in a 55-year-old woman who ingested 1,1'-iminodi (octamethylene) diguanidinium triacetate (iminoctadine triacetate), a fungicide. The fungicide formulation was also composed of polyoxyethylene nonylphenol (NP-40) and methanol. PATIENT CONCERNS: Severe cholestatic hepatitis developed, which led to the patient's death on day 88 of hospitalization. Post-mortem necropsy of the liver showed focal hepatocyte necrosis involving mostly the mid-zone, along with intracytoplasmic and intracanalicular cholestasis. DIAGNOSES: To identify the chemical responsible for hepatic injury, the cellular toxicity of all chemicals in the fungicide formulation was assessed in HepG2 cells using the 3-(4,5-dimethylthiaxol-2yl)-2, 5-diphenyl tetrazolium bromide test. OUTCOMES: Viability of cells treated with the surfactant NP-40 was significantly lower (Pâ<â.001), but that of cells treated with other components of the fungicide, including the active ingredient, iminoctadine triacetate, was unaffected. Fluorescence-activated cell sorting analysis confirmed that necrosis was induced in HepG2 cells treated with 25-80âµM of NP-40, while significant numbers of apoptotic cells were not detected. LESSONS: NP-40 appears to be the chemical responsible for the patient's irreversible hepatic injury, accompanied by intracytoplasmic and intracanalicular cholestasis.
Asunto(s)
Colestasis/inducido químicamente , Colestasis/complicaciones , Hepatitis/etiología , Fenoles/envenenamiento , Polietilenglicoles/envenenamiento , Femenino , Guanidinas/envenenamiento , Humanos , Persona de Mediana EdadRESUMEN
Neonicotinoids are a relatively newer class of insecticide. Used primarily in agriculture, neonicotinoids are also used for flea control in domestic animals. Information on human exposures to neonicotinoids is limited. Neonicotinoid exposures reported to Texas poison centers during 2000-2012 were identified and the distribution by selected factors examined. Of 1,142 total exposures, most products contained imidacloprid (77%) or dinotefuran (17%). The exposures were seasonal with half reported during May-August. The most common routes of exposure were ingestion (51%), dermal (44%), and ocular (11%). The distribution by patient age was 5 years or less (28%), 6-19 years (9%), 20 years or more (61%), and unknown (2%); and 64% of the patients were female. Of all, 97% of the exposures were unintentional and 97% occurred at the patient's own residence. The management site was on-site (92%), already at/en route to a health care facility (6%), and referred to a health care facility (2%). The medical outcomes included no effect (22%), minor effect (11%), moderate effect (1%), not followed judged nontoxic (14%), not followed minimal effects (46%), unable to follow potentially toxic (1%), and unrelated effect (4%). The most commonly reported adverse clinical effects were ocular irritation (6%), dermal irritation (5%), nausea (3%), vomiting (2%), oral irritation (2%), erythema (2%), and red eye (2%). The most frequently reported treatments were dilution/wash (85%) and food (6%). In summary, these data suggest that the majority of neonicotinoid exposures reported to the poison centers may be managed outside of health care facilities with few clinical effects expected.
Asunto(s)
Guanidinas/envenenamiento , Imidazoles/envenenamiento , Insecticidas/envenenamiento , Nitrocompuestos/envenenamiento , Centros de Control de Intoxicaciones , Intoxicación/terapia , Adolescente , Distribución por Edad , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Masculino , Neonicotinoides , Intoxicación/diagnóstico , Intoxicación/epidemiología , Pronóstico , Estudios Retrospectivos , Distribución por Sexo , Factores Sexuales , Texas/epidemiología , Adulto JovenAsunto(s)
Abejas/efectos de los fármacos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Insecticidas/toxicidad , Incertidumbre , Animales , Abejas/parasitología , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente , Europa (Continente) , Guanidinas/envenenamiento , Guanidinas/toxicidad , Imidazoles/envenenamiento , Imidazoles/toxicidad , Insecticidas/administración & dosificación , Insecticidas/envenenamiento , Neonicotinoides , Nitrocompuestos/envenenamiento , Nitrocompuestos/toxicidad , Oxazinas/envenenamiento , Oxazinas/toxicidad , Medición de Riesgo , Tiametoxam , Tiazoles/envenenamiento , Tiazoles/toxicidadAsunto(s)
Abejas/fisiología , Política Ambiental , Formulación de Políticas , Revelación de la Verdad , Animales , Abejas/efectos de los fármacos , Conservación de los Recursos Naturales/métodos , Unión Europea , Guanidinas/envenenamiento , Imidazoles/envenenamiento , Insecticidas/envenenamiento , Neonicotinoides , Nitrocompuestos/envenenamiento , Oxazinas/envenenamiento , Dinámica Poblacional , Tiametoxam , Tiazoles/envenenamiento , Reino UnidoAsunto(s)
Agaricales/química , Hipoglucemia/inducido químicamente , Intoxicación por Setas/metabolismo , Micotoxinas/envenenamiento , Miocardio/metabolismo , Aminoácidos/aislamiento & purificación , Aminoácidos/envenenamiento , Animales , China , Ácidos Grasos/metabolismo , Guanidinas/aislamiento & purificación , Guanidinas/envenenamiento , Corazón/efectos de los fármacos , Humanos , Ratones , EstereoisomerismoAsunto(s)
Bebidas Alcohólicas/envenenamiento , Depresores del Sistema Nervioso Central/envenenamiento , Etanol/envenenamiento , Adolescente , Adulto , Alcoholismo/epidemiología , Alcoholismo/mortalidad , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Desinfectantes/envenenamiento , Femenino , Guanidinas/envenenamiento , Humanos , Masculino , Persona de Mediana Edad , Intoxicación/epidemiología , Intoxicación/terapia , Federación de Rusia/epidemiología , Adulto JovenRESUMEN
INTRODUCTION: Polyhexamethyleneguanidine hydrochloride (PHMG) is an antimicrobial biocide of the guanidine family. In the period from August 2006 to May 2007, more than 12500 patients were admitted to hospital with a history of drinking illegal cheap "vodka" in 44 different regions in Russia, of whom 9.4% died. In reality, the "vodka" was an antiseptic liquid composed of ethanol (≈93%), diethyl phthalate, and 0.1-0.14% PHMG (brand name "Extrasept-1"). MATERIAL AND METHODS: We performed an analysis of the clinical features and outcome in four poisoning treatment centers in the cities of Perm, Ekaterinburg, Irkutsk, and Khabarovsk. A total of 579 patients (215 females and 364 males) with similar symptoms were included. RESULTS: The main symptoms on admission included jaundice (99.7%), skin itch (78.4%), weakness (96%), anorexia (65.8%), dizziness (65.3%), nausea (54.8%), vomiting (22.6%), stomach ache (52.7%), diarrhea (32%), and fever (50%). Mild symptoms were found in 2.5% of cases, moderate in 63%, and severe in 34.5%. Laboratory results were (mean ± SD): total bilirubin 249 ± 158 µmol/L, direct bilirubin 166 ± 97 µmol/L, cholesterol 14 ± 8 mmol/L, alanine aminotransferase 207 ± 174 IU/L, aspartate aminotransferase 174 ± 230 IU/L, alkaline phosphatase 742 ± 751 IU/L, and gamma-glutamyltranspeptidase 1199 ± 1095 IU/L. Patients generally recovered over a period of 1-5 months, although high levels of alkaline phosphatase and gamma-glutamyltranspeptidase were still found in all patients examined after 6 months. Sixty-one patients (10.5%) died between 23 and 150 days after poisoning. Local cholestasis, inflammatory infiltration, and fibrosis developing into cirrhosis were found by liver biopsy. CONCLUSION: Acute liver injury caused by PHMG-hydrochloride or PHMG in combination with either ethanol or diethyl phthalate can be characterized as cholestatic hepatitis with a severe inflammatory component causing high mortality.
Asunto(s)
Depresores del Sistema Nervioso Central/envenenamiento , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Colestasis/patología , Desinfectantes/envenenamiento , Etanol/envenenamiento , Guanidinas/envenenamiento , Enfermedad Aguda , Adolescente , Adulto , Factores de Edad , Anciano , Bebidas Alcohólicas/envenenamiento , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico por imagen , Colestasis/diagnóstico por imagen , Técnicas de Laboratorio Clínico , Epidemias , Femenino , Encefalopatía Hepática/inducido químicamente , Encefalopatía Hepática/psicología , Humanos , Hígado/patología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Intoxicación/diagnóstico , Intoxicación/epidemiología , Intoxicación/mortalidad , Estudios Retrospectivos , Federación de Rusia/epidemiología , Factores Sexuales , Clase Social , Ultrasonografía , Adulto JovenRESUMEN
Alcoholism remains one of the main causes of premature death in the population of Russia. Hence, the importance of the problem of uncontrolled distribution and consumption of surrogate alcoholic products, such as alcohol-containing liquids of uncertain origin. The objective of the present study was to detect ethyl alcohol, polyhexamethylene guanidine hydrochloride, and diethylphthalate in disinfectant liquids, biological fluids and human tissues and to analyse qualitative and quantitative composition of these materials.
Asunto(s)
Alcoholes/análisis , Detergentes/química , Patologia Forense/métodos , Toxicología Forense/métodos , Guanidinas/análisis , Ácidos Ftálicos/análisis , Alcoholes/química , Alcoholes/envenenamiento , Líquidos Corporales/química , Detergentes/envenenamiento , Guanidinas/química , Guanidinas/envenenamiento , Humanos , Estructura Molecular , Ácidos Ftálicos/química , Ácidos Ftálicos/envenenamiento , Intoxicación/sangre , Intoxicación/patologíaRESUMEN
Medical cards of 1,116 inpatient victims of surrogate alcohol poisoning and 242 cases of its fatal outcome associated with jaundice were available for analysis form Irkutsk Region and other regions of the Russian Federation in the second half of 2006 and early 2007. The study revealed differences in hepatic lesions depending on the chemical nature of toxicants. Mixtures containing guanidine derivatives caused highly specific irreversible disturbance of bile transport in hepatocytes and biliary capillaries in the absence of cholestasis at the level of biliary ducts. Changes in hepatocytes of different type and genesis appear to be due to other toxic components and may be of use for the establishment of causal relation between hepatic lesions and concrete toxic mixtures.
Asunto(s)
Bebidas Alcohólicas/envenenamiento , Enfermedad Hepática Inducida por Sustancias y Drogas , Medicina Legal , Guanidinas/envenenamiento , Hígado , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Femenino , Humanos , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Necrosis , Intoxicación/complicaciones , Intoxicación/patologíaRESUMEN
Iminoctadine, a fungicide used widely in fruit culture, causes hypotension in human acute oral poisoning. In an attempt to elucidate this mechanism, we investigated the effects of iminoctadine on the cardiovascular system of rats. In anesthetized rats, intravenously administered iminoctadine produced hypotension and tachycardia. In isolated right atria beating spontaneously in Krebs-Ringer's solution, iminoctadine produced an increase in heart rate. It also produced a positive inotropic response in electrically driven left atria. These responses were partially diminished by atenolol, a beta 1-adrenoceptor antagonist, and also partially diminished to a similar degree in atria of reserpinized rats. Therefore, the positive inotropic and chronotropic effects of iminoctadine were partially mediated via the release of norepinephrine from sympathetic nerve terminals. In aortic ring segments, iminoctadine caused a rightward shift of the concentration-contractile response curve for phenylephrine but did not affect those for prostaglandin F2 alpha or KCl. Iminoctadine produced a potent vasodilation in aortic segments precontracted with phenylephrine. Removal of the aortic endothelium produced a rightward shift of the concentration-response curve for iminoctadine. When the aortic ring preparations were precontracted with prostaglandin F2 alpha or KCl, iminoctadine produced only slight vasodilation. Therefore, the vasodilation caused by iminoctadine is due mostly to its alpha 1-adrenoceptor antagonizing action, and partly to endothelium-dependent mechanisms our data suggest that the hypotension induced by iminoctadine is due to its vasodilator effects.
Asunto(s)
Fungicidas Industriales/envenenamiento , Guanidinas/envenenamiento , Hipotensión/fisiopatología , Animales , Aorta Torácica/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Dinoprost/farmacología , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Hipotensión/inducido químicamente , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Terminaciones Nerviosas/efectos de los fármacos , Intoxicación/fisiopatología , Ratas , Ratas WistarRESUMEN
We report a case of a 27-year-old man who ingested a fungicide containing iminoctadine with suicidal intent. He developed acute and severe circulatory failure which responded well to noradrenaline.
Asunto(s)
Enfermedades Cardiovasculares/inducido químicamente , Fungicidas Industriales/envenenamiento , Guanidinas/envenenamiento , Enfermedad Aguda , Adulto , Humanos , MasculinoRESUMEN
Sanitary and toxicological study of some guanidine containing polymers was done. Moderate toxicity of the polymers and absence of any specific effects were noted.
Asunto(s)
Guanidinas/toxicidad , Enfermedad Aguda , Animales , Relación Dosis-Respuesta a Droga , Guanidinas/envenenamiento , Dosificación Letal Mediana , Ratones , Peso Molecular , Intoxicación/sangre , Intoxicación/fisiopatología , Ratas , Factores de TiempoRESUMEN
Blasticidin S is an effective fungicidal aminocylonucleoside antibiotic against a rice blast disease. We presented the first 4 reported cases of acute poisoning from ingesting blasticidin S for suicidal attempts. Three of the patients were fatal. The symptoms observed in the patients included vomiting immediately after ingestion and severe, persistent, watery diarrhea. The toxic effects of blasticidin S were noted in ectodermal tissues including the skin, conjunctiva, cornea, and intestine. Massive loss of intestinal fluid resulted in progressively pronounced hypotension associated with tachycardia. The treatment of choice for the poisoning consists of intravenous fluid administration and the management of body water and electrolyte balance.
Asunto(s)
Antifúngicos/envenenamiento , Adulto , Anciano , Femenino , Guanidinas/envenenamiento , Humanos , Masculino , Persona de Mediana Edad , Nucleósidos , Intento de SuicidioAsunto(s)
Guanabenzo/envenenamiento , Guanidinas/envenenamiento , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Guanadrel sulphate is an orally active peripheral sympathetic inhibitor (adrenergic neuron-blocking drug). In comparative studies, guanadrel was comparable in efficacy with guanethidine or methyldopa in mild to moderately severe hypertension, although generally it caused fewer central nervous system side effects than methyldopa and less orthostatic dizziness and diarrhoea than guanethidine. However, its efficacy in patients whose blood pressure remains inadequately controlled by other drugs (except diuretics alone) has yet to be adequately demonstrated. Guanadrel has a rapid onset of action and a half-life of about 10 hours, thus dose titration can be achieved more rapidly than with guanethidine, and twice daily administration is appropriate. Generally, guanadrel has been well tolerated, withdrawal of treatment due to adverse effects seldom being necessary. Thus, guanadrel appears to be a suitable alternative to methyldopa for the treatment of mild to moderately severe hypertension not controlled adequately by diuretics alone.
Asunto(s)
Antihipertensivos/farmacología , Guanidinas/farmacología , Hipertensión/tratamiento farmacológico , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Antihipertensivos/metabolismo , Antihipertensivos/envenenamiento , Antihipertensivos/uso terapéutico , Sistema Nervioso Central/efectos de los fármacos , Interacciones Farmacológicas , Guanetidina/metabolismo , Guanetidina/uso terapéutico , Guanidinas/administración & dosificación , Guanidinas/efectos adversos , Guanidinas/metabolismo , Guanidinas/envenenamiento , Guanidinas/uso terapéutico , Hemodinámica/efectos de los fármacos , Humanos , Cinética , Metildopa/uso terapéutico , Sistema Nervioso Simpático/efectos de los fármacosAsunto(s)
Guanabenzo/envenenamiento , Guanidinas/envenenamiento , Atropina/uso terapéutico , Bradicardia/inducido químicamente , Preescolar , Dopamina/uso terapéutico , Femenino , Fluidoterapia , Humanos , Hipotensión/inducido químicamente , Persona de Mediana Edad , Naloxona/uso terapéutico , Fases del Sueño/efectos de los fármacosRESUMEN
Frogs were injected for several weeks with beta-guanidinopropionate, an isomer of creatine. Their sartorius muscles were isolated, poisoned with iodoacetate and stimulated isometrically with 75 shocks/min in nitrogen until rigor. In comparison with sartorius muscles of untreated frogs, they contained more free creatine and less phosphocreatine, but the same content in total creatine and ATP. They also contained beta-guanidinopropionate both free and phosphorylated. However, muscles in rigor contained the same concentration of the phosphorylated form as resting muscles, i.e., phospho-beta-guanidinopropionate was not split during contraction. The number of twitches performed before rigor was decreased. There was no change in the chemical energy usage (sum of phosphocreatine breakdown and twice ATP breakdown) per twitch.