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
We report a case series of dopamine dysregulation syndrome, previously known as hedonistic homeostatic dysregulation in patients with Parkinson's disease on dopamine replacement therapies, now designated as Lees' syndrome.
Relatamos uma série de casos da síndrome de desregulação dopaminérgica, previamente conhecida como desregulação homeostática hedonística em pacientes com doença de Parkinson em uso de terapia de reposição dopaminérgica, e agora definida como síndrome de Lees.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Antiparkinson Agents/adverse effects , Dopamine Agents/adverse effects , Dopamine/metabolism , Dyskinesia, Drug-Induced/etiology , Parkinson Disease/drug therapy , Antiparkinson Agents/therapeutic use , Carbidopa/adverse effects , Drug Combinations , Dopamine Agents/therapeutic use , Levodopa/adverse effects , Parkinson Disease/complications , SyndromeABSTRACT
Clozapine has been used as an attempt to manage levodopa complications in advanced Parkinson's disease (PD). To investigate the use of clozapine in this context in a Brazilian sample, a retrospective chart review was carried out at the Movement Disorders Clinic from the Federal University of Minas Gerais. This study enrolled 43 PD patients who used or were in use of clozapine. Patients had a mean age of 64 years and a mean UPDRS score of 55. Clozapine was indicated for dyskinesias in 17 patients, for psychosis in 15 and for both reasons in 11. The average maximum dose was 70 mg/day. Twenty six patients used it for a mean of 3.5 years. Twenty nine presented an improvement of their condition, 9 remained clinically stable. Twenty subjects interrupted the use of clozapine, being 9 due to adverse effects. Clozapine may play a role in the management of motor and psychiatric complications in PD, but it is associated with low tolerability.
A clozapina vem sendo utilizada na doença de Parkinson (DP) avançada para controle das complicações causadas pela levodopa. Com o objetivo de investigar o emprego da clozapina nesse contexto em amostra de pacientes brasileiros, um estudo retrospectivo foi realizado no Ambulatório de Distúrbios do Movimento da Universidade Federal de Minas Gerais. Este estudo incluiu 43 pacientes que usaram clozapina, apresentando idade média de 64 anos e uma média de 55 pontos no UPDRS. A clozapina foi indicada para discinesias em 17 pacientes, para psicose em 15 e para ambos os motivos em 11. A média da dose máxima empregada foi de cerca de 70 mg/dia. Vinte e seis pacientes usaram a medicação por uma média de 3,5 anos. Houve melhora do quadro clínico em 29 pacientes, 9 permaneceram com quadro clínico estático. O tratamento foi interrompido em 20 pessoas, sendo 9 por efeitos adversos. Apesar de a clozapina ser eficaz no controle das complicações motoras e psiquiátricas na DP, seu uso está associado com baixa tolerabilidade.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , Dyskinesia, Drug-Induced/drug therapy , Parkinson Disease/drug therapy , Psychoses, Substance-Induced/drug therapy , Antiparkinson Agents/adverse effects , Antiparkinson Agents/therapeutic use , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Drug Therapy, Combination , Dyskinesia, Drug-Induced/etiology , Levodopa/adverse effects , Levodopa/therapeutic use , Parkinson Disease/psychology , Psychoses, Substance-Induced/etiology , Retrospective StudiesABSTRACT
We carried out a retrospective descriptive study to determine prevalence and risk factors for tardive dyskinesia [TD] among psychotic patients treated with conventional neuroleptics in 4 centres in Saudi Arabia. Records of patients who had been taking
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Dyskinesia, Drug-Induced/etiology , Antipsychotic Agents/adverse effects , Arabs , Risk Factors , Retrospective StudiesABSTRACT
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Dopamine deficit is the cornerstone of its clinical manifestations. Levodopa, the main treatment for this condition, was first used for PD more than 40 years ago and today it still is the most powerful treatment for this disease. In recent years many advances have been made for understanding of the neurochemical mechanisms of this drug. Furthermore, new insights about the genesis of motor complications secondary to its use are known, specially related with the mode of its administration. This article updates the pharmacology of levodopa and its implications for the pathophysiology and treatment of PD. The new available presentations of levodopa are also reviewed. The implications of these advances for the treatment of this disease are commented.
Subject(s)
Humans , Antiparkinson Agents/therapeutic use , Dopamine Agents/therapeutic use , Levodopa/therapeutic use , Parkinson Disease/drug therapy , Antiparkinson Agents/adverse effects , Antiparkinson Agents/pharmacokinetics , Chile , Dopamine Agents/adverse effects , Dopamine Agents/pharmacokinetics , Dyskinesia, Drug-Induced/etiology , Levodopa/adverse effects , Levodopa/pharmacokinetics , Parkinson Disease/metabolism , Parkinson Disease/physiopathologyABSTRACT
Desde la introducción de la levodopa para el manejo de la enfermedad de Parkinson ésta ha sido el tratamiento estándar de esta enfermedad. La aparición de fármacos alternativos como los agonistas dopaminérgicos abrieron un debate acerca de los potenciales beneficios de estas terapias por sobre levodopa y los eventuales efectos deletéreos de esta última. En este artículo se actualiza la información acerca de las complicaciones motoras y de neurotoxicidad inducidas por levodopa.
Subject(s)
Humans , Parkinson Disease/drug therapy , Levodopa/toxicity , Motor Skills Disorders/etiology , Antiparkinson Agents/toxicity , Nerve Degeneration/chemically induced , Dyskinesia, Drug-Induced/etiology , Dyskinesias/drug therapyABSTRACT
We present an unusual case of cerebrotendinous xanthomatosis in a female elderly patient with recurrent TM joint dislocation and oromandibular dyskinesia.
Subject(s)
Biopsy , Dyskinesia, Drug-Induced/etiology , Female , Humans , Middle Aged , Temporomandibular Joint Disorders/etiology , Xanthomatosis, Cerebrotendinous/complicationsABSTRACT
En este trabajo se hace una revisión acerca de disquinesias tardías, temidas complicaciones del uso de antipsicóticos. Clínicamente se presentan de manera polimorfa, aunque tienden a seguir un patrón más o menos característico de acuerdo al sexo y edad del paciente afectado. Su fisiopatología es desconocida, revisándose las principales teorías que al respecto existen en la actualidad, así como los datos epidemiológicos, lo factores de riesgo, el pronóstico, manejo y perspectivas futuras.
Subject(s)
Humans , Dyskinesia, Drug-Induced/diagnosis , Dyskinesia, Drug-Induced/epidemiology , Dyskinesia, Drug-Induced/etiology , Dyskinesia, Drug-Induced/physiopathology , Dyskinesia, Drug-Induced/therapy , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Risk FactorsABSTRACT
Tardive dyskinesia is a serious motor side effect of long term neuroleptic therapy, with an unknown pathophysiological basis. The leading hypothesis of the pathophysiology of tardive dyskinesia includes dopamine receptor supersensitivity, GABAergic hypofunction, excitotoxicity and oxidative stress. Many preclinical models have been developed to identify the underlying pathological processes of tardive dyskinesia, but none has yet produced a parsimonious results. A wide range of animal models, viz. Homologous, analogous and correlational models have been developed to explore the pathophysiology of tardive dyskinesia. Vacuous chewing movements in rodents induced by chronic neuroleptic treatment is the most frequently employed model. As the existing models suffer from several phenomenological and methodological problems, development of new models, highly predictive of pathological basis of tardive dyskinesia can accelerate tardive dyskinesia research for the better understanding of the pathophysiological processes underlying the syndrome and for the discovery of new therapeutic targets for the treatment of tardive dyskinesia.
Subject(s)
Animals , Antipsychotic Agents/adverse effects , Disease Models, Animal , Dyskinesia, Drug-Induced/etiology , Free Radicals , Humans , Isoniazid/adverse effects , Receptors, Dopamine/drug effects , Reserpine/adverse effects , gamma-Aminobutyric Acid/physiologyABSTRACT
A ocorrência de discinesias dificulta consideravelmente o manuseio terapêutico dos pacientes parkinsonianos tratados como levodopa. Estudamos asa caracrísticas clínicas das discinesias em 176 pacientes com diagnóstico de doença de Parkinson e tratados com levodopa. As discinesias ocorreram, em média, após 6,2 anos de duraçao da doença a após 4,2 anos de tratamento como levodopa. A maioris dos pacientes (90 por cento) achava-se nos estágios II e III de Hoehn & Yahr por ocasiao do início das discinesias. As discinesiasmais frequentes foram de "pico de dose" e "contínua". Movimento do tipo distônico ocorreu em 40 por cento dos casos e predominou nas discinesias de "fim de dose" e "bifásica". Distonia matinal correspondeu a 35 por cento dos casos de distonia. Movimentos coreiformes se manifestaram de forma gerenalizada em 43,2 por cento dos casos. Movimentos distônicos predominaram nos membros inferiores. A discinesia, qunado unilateral, ocorreu mais frequentemente no hemicorpo mais comprometido pela doença de Parkinson. A discinesia orofacial, quando isolada, foi mais frequentes nos pacientes mais idosos.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Parkinson Disease/drug therapy , Dyskinesia, Drug-Induced/etiology , Levodopa/adverse effects , Age Factors , Aged, 80 and over , Dose-Response Relationship, Drug , Levodopa/administration & dosage , Levodopa/therapeutic use , Retrospective Studies , Time FactorsABSTRACT
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/pharmacologySubject(s)
Adult , Akathisia, Drug-Induced , Antacids/adverse effects , Antiemetics/adverse effects , Dopamine Antagonists , Duodenal Ulcer/drug therapy , Dyskinesia, Drug-Induced/etiology , Dystonia/chemically induced , Female , Histamine H2 Antagonists/adverse effects , Humans , Receptors, Dopamine/drug effects , Time FactorsSubject(s)
Adult , Diet, Vegetarian , Dyskinesia, Drug-Induced/etiology , Female , Humans , Male , Metoclopramide/adverse effects , Middle Aged , Vomiting/drug therapyABSTRACT
Two hundred and thirty-two psychiatric Outpatients on depor fluphenazine decanoate for more than six months were examined for Tardive Dyskinesia (TD), using the AIMS rating scale, and the prevalence rates of TD at different criteria of severity were asssessed. The prevalence rates ranged from 7% for patients with asevere TD to 45% for patients with any degree of TD. The sex distribution of patients with TD showed no bias but the female patients were significantly older than the male patients. Increases in prevalence rats of TD were associated with the combination of an anticholinergic anti-Parkinsonian drug with the depot neuroleptic, and with the concomitant use of an oral neuroleptic with the depot preparation. Implications of these finding for the long-term management of schizopherinia are discussed
Subject(s)
Adult , Middle Aged , Humans , Male , Female , Antipsychotic Agents/adverse effects , Dyskinesia, Drug-Induced/etiology , Mental Disorders/drug therapy , Ambulatory Care , Schizophrenia/drug therapy , Aged, 80 and over , Fluphenazine/analogs & derivatives , Fluphenazine/adverse effects , Delayed-Action PreparationsABSTRACT
Três pacientes em uso de amiodarona para tratamento de arritmia cardíaca refratária apresentaram manifestaçöes neurológicas. Dois desenvolveram quadro polineurítico após 4 e 6 anos de uso do medicamento. O terceiro apresentou quadro de discinesia associado a grau moderado de neuropatia e ataxia após 2 meses de uso de amiodarona. A biopsia do nervo sural em dois casos revelou rarefaçäo axonal associada a inclusöes lamelares e corpos densos, osmioílicos nas células de Schwann e no endotélio venular (um paciente). A interrupçäo do uso do cloridrato de amiodarona provocou regressäo dos sintomas neurológicos