RESUMEN
Organophosphorus (OP) used as pesticides and hydraulic fluids can produce acute poisoning known as OP-induced delayed neuropathy (OPIDN), whose effects take long time to recover. Thus a secure therapeutic strategy to prevent the most serious effects of this poisoning would be welcome. In this study, tri-o-cresyl phosphate (TOCP, 500 mg/kg p.o.) was given to hens, followed or not by nimodipine (1mg/kg i.m.) and calcium gluconate (Ca-glu 5mg/kg i.v.). Six hours after TOCP intoxication, neuropathy target esterase (NTE) activity inhibition was observed, peaking after 24h exceeding 80% inhibition. A fall in the plasmatic calcium levels was noted 12h after TOCP was given and, in the sciatic nerve, Ca(2+) fell 56.4% 24h later; at the same time calcium activated neutral protease (CANP) activity increased 308.7%, an effect that lasted 14 days. Any bird that received therapeutic treatment after TOCP intoxication presented significant signs of OPIDN. These results suggest that NTE may be implicated in the regulation of calcium entrance into cells being responsible for the maintenance of normal function of calcium channels, and that increasing CANP activity is responsible to triggering OPIDN. Thus, with one suitably adjusted dose of nimodipine as well as Ca-glu, we believe that this treatment strategy may be used in humans with acute poisoning by neuropathic OP.
Asunto(s)
Enfermedades del Sistema Nervioso/inducido químicamente , Plaguicidas/envenenamiento , Tritolilfosfatos/envenenamiento , Animales , Calcio/sangre , Calcio/metabolismo , Canales de Calcio/efectos de los fármacos , Canales de Calcio/metabolismo , Gluconato de Calcio/uso terapéutico , Hidrolasas de Éster Carboxílico/antagonistas & inhibidores , Hidrolasas de Éster Carboxílico/metabolismo , Pollos/metabolismo , Modelos Animales de Enfermedad , Homeostasis/efectos de los fármacos , Músculos/metabolismo , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/metabolismo , Nimodipina/uso terapéuticoRESUMEN
To examine the efficacy of calcium gluconate (two doses of Ca-Glu 5 mg/kg i.v.) to alleviate the injurious effects of organophosphorus induced delayed neuropathy (OPIDN) in the presence or absence of phenylmethanesulfonyl fluoride (PMSF 90 mg/kg i.m.), 14 groups of four isabrown hens were used. To measure the lymphocyte neuropathy target esterase (LNTE)activity, groups receiving just distilled water (control), groups receiving just Tri-orto-cresyl phosphate (TOCP; 500 mg/kg p.o.) (Positive control), and other groups receiving TOCP and Ca-Glu or PMSF simultaneously or 12 hours later following intoxication by TOCP were used. They were sacrificed 12 and 24 hours after the administration of TOCP. To observe a 28-day time course of neurotoxicity scores and calcium plasma concentration, five groups were used. Regarding free Ca(2+)in the plasma, the positive control produced a characteristic profile time course up and down during 28 days, and some hens with maximum score of neurotoxicity in 28 days. The treatment, which prevented greater oscillation in free Ca(2+) in the plasma, presented a decrease in OPIDN in relation to the positive control. Twelve hours after the administration of TOCP, LNTE was 70-80% inhibited when compared with control, whereas the first decrease in the free Ca(2+) in the plasma was significantly different from the control only 24 hours after the administration of TOCP. In summary, the sooner the Ca-Glu is started, the less severe the neuropathy effects.
Asunto(s)
Gluconato de Calcio/uso terapéutico , Fluoruro de Fenilmetilsulfonilo/uso terapéutico , Tritolilfosfatos/envenenamiento , Enfermedad Aguda , Animales , Calcio/sangre , Hidrolasas de Éster Carboxílico/antagonistas & inhibidores , Pollos , Síndromes de Neurotoxicidad/tratamiento farmacológicoAsunto(s)
Cresoles/envenenamiento , Brotes de Enfermedades/epidemiología , Parálisis/inducido químicamente , Extractos Vegetales/envenenamiento , Tritolilfosfatos/envenenamiento , Bebidas/efectos adversos , Brotes de Enfermedades/historia , Contaminación de Medicamentos , Historia del Siglo XX , Humanos , Jamaica , Legislación de Medicamentos , Parálisis/epidemiología , Parálisis/historiaRESUMEN
In 1930, thousands of Americans were poisoned by an illicit extract of Jamaica ginger ("jake") used to circumvent the Prohibition laws. A neurotoxic organophosphate compound, triorthocresyl phosphate (TOCP), had been used as an adulterant. The earliest reports were of peripheral neuritis, but later it was evident that an upper motor neuron syndrome had supervened. This TOCP poisoning apparently involved various cell groups and tracts in the spinal cord; the lesions was not peripheral at all. We interviewed 11 survivors of the illness residing in eastern Tennessee. Four were carefully examined. The principal findings showed the spasticity and abnormal reflexes of an upper motor neuron syndrome. One patient had mild disease, despite typical findings, and had lived a normal life.