RESUMO
The neuromuscular junction activity of Oxyuranus scutellatus venom and its presynaptic neurotoxin, taipoxin, and their neutralization by two antivenoms were examined in mouse phrenic nerve-diaphragm preparations. The action of taipoxin was also studied at 21°C. The efficacy of the antivenoms was also assessed in an in vivo mouse model. Both antivenoms were effective in neutralizing the neuromuscular blocking activity in preincubation-type experiments. In experiments involving independent addition of venom and antivenoms, neutralization depended on the time interval between venom addition and antivenom application. When taipoxin was incubated for 5, 10 or 20min at 21°C, and antivenom added and temperature increased to 37°C, neutralization was achieved only when the toxin was incubated for 5 or 10min. The neutralization by the two antivenoms in an in vivo model showed that both whole IgG and F(ab')2 antivenoms were effective in neutralizing lethality. Our findings highlight the very rapid action of taipan venom at the nerve terminal, and the poor capacity of antivenoms to revert neurotoxicity as the time interval between venom or taipoxin application and antivenom addition increased. Additionally the disparity between molecular masses of the active substances of the two antivenoms did not result in differences in neutralization.
Assuntos
Antivenenos/farmacologia , Venenos Elapídicos/antagonistas & inibidores , Venenos Elapídicos/toxicidade , Elapidae , Fragmentos Fab das Imunoglobulinas/farmacologia , Imunoglobulina G/farmacologia , Doenças Neuromusculares/induzido quimicamente , Doenças Neuromusculares/prevenção & controle , Junção Neuromuscular/efeitos dos fármacos , Neurotoxinas/antagonistas & inibidores , Neurotoxinas/toxicidade , Animais , Diafragma/efeitos dos fármacos , Técnicas In Vitro , Dose Letal Mediana , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , Nervo Frênico/efeitos dos fármacos , TemperaturaRESUMO
La amiodarona es utilizada frecuentemente en el control de las arritmias cardíacas a pesar de sus múltiples efectos colaterales. Se reporta el caso de un varón de 38 años con diagnóstico de taquicardia ventricular que después de un año de uso crónico de amiodarona, presentó fatiga muscular, parestesias y temblor fino fistal en extremidades. Un aumento en la dosis de amiodarona por recidiva de la arritmia fue seguido de una elevación sostenida de los niveles séricos de la fracción MM de creatín fosfocinasa. Una electromiografia reveló neuropatía periférica sensitivo-motora, y una biopsia del cuadriceps, atrofia muscular de tipo neuropático, que se correlacionó con la presencia de depósitos intralisosomales e importante degeneración axonal en el nervio sural. Ambas alteraciones fueron dosis/tiempo dependiente. El caso ilustra la conveniencia de investigar intencionadamente estas alteraciones en pacientes que reciben este fármaco por periodos prolongados
Assuntos
Humanos , Masculino , Adulto , Antiarrítmicos/efeitos adversos , Amiodarona/efeitos adversos , Amiodarona/farmacologia , Condução Nervosa , Creatina Quinase/sangue , Corpos de Inclusão/ultraestrutura , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacologia , Lisossomos/enzimologia , Lisossomos/ultraestrutura , Músculo Esquelético/patologia , Degeneração Neural , Doenças Neuromusculares/sangue , Doenças Neuromusculares/induzido quimicamente , Doenças Neuromusculares/patologia , Parestesia/induzido quimicamente , Fosfolipases/antagonistas & inibidores , Taquicardia Ventricular/tratamento farmacológicoRESUMO
Amiodarone is a drug broadly used on cardiac arrhythmias despite its multiple side-effects. We present the case of an adult male with symptomatic ventricular tachycardia, receiving longterm amiodarone, who showed increased CK serum levels, sensorimotor neuropathy and secondary myopathy. Quadriceps biopsy showed atrophic changes and sural nerve intralysosomal deposits with intense axonal degeneration. The case illustrates the need to investigate and monitor peripheral neuropathy and muscular atrophy in chronic amiodarone use.
Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Doenças Neuromusculares/induzido quimicamente , Adulto , Amiodarona/farmacologia , Atrofia , Creatina Quinase/sangue , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacologia , Humanos , Corpos de Inclusão/ultraestrutura , Isoenzimas , Lisossomos/enzimologia , Lisossomos/ultraestrutura , Masculino , Músculo Esquelético/patologia , Degeneração Neural , Condução Nervosa , Doenças Neuromusculares/sangue , Doenças Neuromusculares/patologia , Parestesia/induzido quimicamente , Fosfolipases/antagonistas & inibidores , Nervo Sural/patologia , Taquicardia Ventricular/tratamento farmacológicoRESUMO
The effects of low lead exposure were investigated in 96 children (7-12 years old) living and studying within a 1 km radius of a lead smelter (exposed population) located in Torreón, Coahuila, México, and compared with 30 children living and studying 4.5 km from the same smelter (control population). Both populations had similar socio-economic conditions. The exposed population showed higher blood lead (PbB) and free erythrocyte protoporphyrin (FEP) concentrations (17.3 +/- 5.6 micrograms dl-1 and 53.9 +/- 46.1 micrograms dl-1, respectively) than controls (PbB, 5.4 +/- 3.1 micrograms dl-1 and FEP, 13.9 +/- 7.3 micrograms dl-1). PbB concentrations were inversely correlated to distance from the smelter (r2 = 0.494). However, in the exposed population, wind direction also had a significant effect on the PbB and urinary lead (PbU) concentrations. The exposed population was divided according to PbB into a high level lead group (PbB > 15 micrograms dl-1), which also showed high FEP concentrations and a low lead group (PbB < 15 micrograms dl-1). Clinically, the high lead group showed a greater incidence of general symptoms (colic, headache, paresthesia, myalgia and dizziness), impairment of some neuromuscular functions (neuromuscular conduction velocity and motor coordination) and a decrease of intelligence quotient (IQ), which was not related with sex or socio-economic status. These results are an evidence of morbidity in children with high PbB concentrations.
Assuntos
Exposição Ambiental/efeitos adversos , Chumbo/efeitos adversos , Chumbo/sangue , Criança , Cólica/induzido quimicamente , Feminino , Cefaleia/induzido quimicamente , Humanos , Chumbo/urina , Modelos Lineares , Masculino , México , Doenças Neuromusculares/induzido quimicamente , Parestesia/induzido quimicamente , Protoporfirinas/sangueAssuntos
Asma/tratamento farmacológico , Metaproterenol/administração & dosagem , Administração Oral , Resistência das Vias Respiratórias/efeitos dos fármacos , Asma/fisiopatologia , Criança , Pré-Escolar , Método Duplo-Cego , Esquema de Medicação , Avaliação de Medicamentos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Metaproterenol/efeitos adversos , Métodos , Doenças Neuromusculares/induzido quimicamente , Distribuição AleatóriaRESUMO
A case of 38 year old man who worked with organochlorinated and Parathion during 5 years is reported. His follow-up was up to 2 years. The onset of the disease was characterized by cholinergic signs, headache, loss of weight, trembling, miokimias, fasciculations, ataxia, myotonic phenomena (in hands only) and motor sensitive peripheral polyneuropathy (affecting the lower limbs symmetrically). Low concentrations of blood cholinesterases confirmed the etiology. Myotonic phenomena disappeared spontaneously 6 months after the initial observation. One year later, the concentration of erythrocyte acetylcholinesterase was found to be low and plasma cholinesterase was normal, suggesting that the patient was carrier of a congenital deficiency of acetylcholinesterase. In literature relationship between myotonia and intoxication due to organophosphorus was not found. The whole clinical picture, cholinergic symptoms, transitory phenomena and spontaneous motor activity could be explained by an excess of acetylcholine. Electromyography (EMG) in the first observation showed neuromuscular transmission blocking characterized by deficiency or absence of voluntary activity, unexcitability of fibular nerves, with fibrillations and positive peaks as described previously with Mipafox (another organophosphorus agent). During 2 years of observation numerous end-plates potentials of muscular fibres persisted in the EMG. A progressive increase in voluntary activity showed by unit motor potential of almost normal amplitude and very increased duration was observed. No potentials of reinnervation were noted. The results of EMG were explained as disturbances of neuromuscular transmission associated with moderate signs of denervation. The Eaton-Lambert's test and the stimulation of a single unit motor potential confirmed disorder of neuromuscular synapses. The histochemistry of brachial biceps showed scattered atrophic and angulated type I and II fibres. Teased-fibres preparations showed nerve fibres with B, C, and G alterations as defined by Dyck et al. indicating axonal degeneration. These results were according to velocity of sensitive conduction. The conduction velocity of fibular nerves was strongly delayed during all the evolution indicating serious disorders of motor nerves myelin.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Colinesterases/sangue , Doenças Neuromusculares/induzido quimicamente , Paration/intoxicação , Acetilcolina/sangue , Adulto , Eletromiografia , Humanos , Masculino , Músculos/patologia , Condução Nervosa , Nervo Sural/patologiaAssuntos
Amicacina/farmacologia , Antibacterianos/farmacologia , Gentamicinas/farmacologia , Doenças do Recém-Nascido/induzido quimicamente , Canamicina/análogos & derivados , Sulfato de Magnésio/efeitos adversos , Doenças Neuromusculares/induzido quimicamente , Tobramicina/farmacologia , Adolescente , Animais , Sinergismo Farmacológico , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/terapia , Intubação Intratraqueal , Masculino , Camundongos , Camundongos Endogâmicos , Doenças Neuromusculares/terapia , Coelhos , Insuficiência Respiratória/induzido quimicamente , Insuficiência Respiratória/terapiaRESUMO
Blindness is one of the most serious side effects of treatment with drugs. We report a case of a young man who became blind and developed weakness of the legs after inappropriate use of dapsone. This is the first report of optic atrophy in association with daposone.