ABSTRACT
BACKGROUND: Chitosan, the N-deacetylated derivative of chitin, is a cationic polyelectrolyte due to the presence of amino groups, one of the few occurring in nature. The use of chitosan in protein and drug delivery systems is being actively researched and reported in the literature RESULTS: In this study, we used chitosan-coated levodopa liposomes to investigate the behavioral character and the expression of phosphorylated extracellular signal-regulated kinase (ERK1/2), dopamine- and cAMP-regulated phos-phoprotein of 32 kDa (DARPP-32) and FosB/AFosB in striatum of rat model of levodopa-induced dyskinesia (LID). We found that scores of abnormal involuntary movement (AIM) decreased significantly in liposome group (P < 0.05), compared with levodopa group. Levels of phospho-ERK1/2, phospho-Thr34 DARPP-32 and FosB/AFosB in striatum decreased significantly in liposome group lesion side compared with levodopa group (P < 0.05). However, both of two groups above have significantly differences compared with the control group (P < 0.05). CONCLUSION: Chitosan-coated levodopa liposomes may be useful in reducing dyskinesias inducing for Parkinson disease. The mechanism might be involved the pathway of signaling molecular phospho-ERK1/2, phospho-Thr34 DARPP-32 and AFosB in striatum
Subject(s)
Animals , Male , Dopamine Agents/pharmacology , Levodopa/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Chitosan/pharmacology , Dyskinesia, Drug-Induced/metabolism , Dyskinesia, Drug-Induced/prevention & control , Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism , Parkinson Disease/drug therapy , Phosphorylation/drug effects , Biocompatible Materials/pharmacology , Immunohistochemistry , Random Allocation , Blotting, Western , Reproducibility of Results , Treatment Outcome , Proto-Oncogene Proteins c-fos/analysis , Proto-Oncogene Proteins c-fos/drug effects , Rats, Sprague-Dawley , Corpus Striatum/drug effects , MAP Kinase Signaling System , Extracellular Signal-Regulated MAP Kinases/analysis , Extracellular Signal-Regulated MAP Kinases/drug effects , Dyskinesia, Drug-Induced/etiology , Dopamine and cAMP-Regulated Phosphoprotein 32/analysis , Dopamine and cAMP-Regulated Phosphoprotein 32/drug effects , Nanoparticles , LiposomesABSTRACT
Effect of active tannoid principles of E. officinalis, comprising of emblicanin A (37%), emblicanin B (33%), punigluconin (12%) and pedunculagin (14%), was investigated on a rat model of tardive dyskinesia (TD) induced by once daily administration of haloperidol (1.5 mg/kg, ip) for 28 days. Involuntary orofacial movements (chewing movements, buccal tremors and tongue protusion) were assessed as TD parameters. The tannoid principles of E. officinalis (EOT) were administered concomitantly with haloperidol in the doses of 10, 20 and 50 mg/kg, po, for 28 days. Sodium valproate (200 mg/kg, po), a Gaba-mimetic agent, and vitamin E (400 mg/kg, po), an antioxidant, were used as the standard drugs and administered for the same period. EOT induced a dose-related inhibition of all the three TD parameters assessed, as did vitamin E. The effect of sodium valproate remained statistically insignificant. The results suggest that EOT exerts a prophylactive effect against neuroleptic-induced TD which is likely to be due to its earlier reported antioxidant effects in rat brain areas, including striatum.
Subject(s)
Animals , Anti-Dyskinesia Agents/pharmacology , Anticonvulsants/pharmacology , Antioxidants/pharmacology , Brain/drug effects , Disease Models, Animal , Dyskinesia, Drug-Induced/prevention & control , Euphorbiaceae/chemistry , GABA Modulators/pharmacology , Haloperidol/pharmacology , Male , Phytotherapy , Plant Extracts/chemistry , Plant Roots/chemistry , Rats , Rats, Wistar , Tannins/pharmacology , Valproic Acid/pharmacology , Vitamin E/pharmacologyABSTRACT
E apresentado um caso de discinesia tardia em uma menina de 7 anos de idade, que desde os 18 meses de idade faz uso de propericiazina. Faz-se breve revisao de literatura recente relativa a esta entidade na infancia. O motivo da consulta e a historia pregressa sao apresentados, bem como o quadro clinico encontrado e o tratamento realizado. E discutido o diagnostico enfatizando-se o diferencial com distonia e sindrome paradoxal da discenia tardia. Ao final, fazem-se recomendacoes
Subject(s)
Humans , Child , Dyskinesia, Drug-Induced/diagnosis , Dyskinesia, Drug-Induced/etiology , Dyskinesia, Drug-Induced/history , Dyskinesia, Drug-Induced/prevention & control , Dyskinesia, Drug-Induced/therapy , Antipsychotic Agents/adverse effects , Antipsychotic Agents/pharmacologyABSTRACT
A discinesia tardia (DT) representa uma séria complicaçäo da terapia neuroléptica, pela sua irreversibilidade, ausência de tratamento e natureza iatrogênica. O autor, neste artigo, realizas uma breve revizäo do tema, abordando os aspectos clínicos, epidemiológicos, fisiopatológico e terapeuticos, enfatizando a prevençäo e o uso criterioso dos neurolépticos como a melhor estratégia de tratamento da síndrome
Subject(s)
Antipsychotic Agents/adverse effects , Dyskinesia, Drug-Induced/physiopathology , Dyskinesia, Drug-Induced/prevention & controlABSTRACT
La discinesia tardía (DT) consiste en movimientos involuntarios persistentes asociados al uso prolongado de fármacos neurolépticos. La frecuencia estimativa de esta alteración es de 10 - 15%. Los ancianos tienen mayor riesgo que aquellos de menos de 50 años. Aunque es de causa desconocida, el aumento de la sensibilidad de los receptores dopaminérgicos en los ganglios basales, explica en parte la fisiopatología de esta alteración. No se dispone de un tratamiento corrientemente satisfactorio, pero el reconocimiento precoz de la DT y la pronta supresión del neuroléptico cuando es indicado puede reducir la incidencia de esta alteración. La prevención es esencial y depende de un diagnóstico psiquiátrico preciso y del uso de neurolépticos solo en indicaciones específicas.