Assuntos
Antiparkinsonianos/efeitos adversos , Nutrição Enteral/efeitos adversos , Levodopa/efeitos adversos , Hipertermia Maligna/etiologia , Síndrome Maligna Neuroléptica/etiologia , Síndrome de Abstinência a Substâncias/complicações , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Esquema de Medicação , Interações Medicamentosas , Seguimentos , Humanos , Intubação Gastrointestinal/métodos , Masculino , Período Pós-OperatórioRESUMO
The cation-independent mannose 6-phosphate receptor is a multifunctional protein which binds at the cell surface to two distinct classes of ligands, the mannose 6-phosphate (M6P) bearing proteins and IGF-II. Its major function is to bind and transport M6P-enzymes to lysosomes, but it can also modulate the activity of a variety of extracellular M6P-glycoproteins (i.e., latent TGFbeta precursor, urokinase-type plasminogen activator receptor, Granzyme B, growth factors, Herpes virus). The purpose of this review is to highlight the synthesis and potential use of high affinity M6P analogues able to target this receptor. Several M6P analogues with phosphonate, carboxylate or malonate groups display a higher affinity and a stronger stability in human serum than M6P itself. These derivatives could be used to favour the delivery of specific therapeutic compounds to lysosomes, notably in enzyme replacement therapies of lysosomal diseases or in neoplastic drug targeting. In addition, their potential applications in preventing clinical disorders, which are associated with the activities of other M6P-proteins involved in wound healing, cell growth or viral infection, will be discussed.
Assuntos
Manosefosfatos/uso terapêutico , Receptor IGF Tipo 2/metabolismo , Sítios de Ligação , Glicoproteínas/metabolismo , Humanos , Lisossomos/metabolismo , Lisossomos/patologia , Manosefosfatos/química , Manosefosfatos/metabolismo , Neoplasias/tratamento farmacológico , Receptor IGF Tipo 2/agonistas , Receptor IGF Tipo 2/químicaRESUMO
Amphiphysin, a synaptic vesicle protein, is an auto-immune target in rare cases of paraneoplastic neurological disorders. We report two additional cases with distinct neurological syndromes and paraneoplastic anti-amphiphysin antibodies. The first patient, a 59-year-old man, presented with cerebellar and cranial nerve dysfunction and small cell lung carcinoma. The second, a 77-year- old woman, presented with left brachial plexopathy followed by sensorimotor neuropathy and breast carcinoma.
Assuntos
Doenças Autoimunes/diagnóstico , Neuropatias do Plexo Braquial/diagnóstico , Encefalite/diagnóstico , Proteínas do Tecido Nervoso/imunologia , Síndromes Paraneoplásicas/diagnóstico , Rombencéfalo , Idoso , Doenças Autoimunes/imunologia , Plexo Braquial/imunologia , Plexo Braquial/patologia , Neuropatias do Plexo Braquial/imunologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/imunologia , Ataxia Cerebelar/diagnóstico , Ataxia Cerebelar/imunologia , Doenças dos Nervos Cranianos/diagnóstico , Doenças dos Nervos Cranianos/imunologia , Encefalite/imunologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Metástase Linfática/diagnóstico , Metástase Linfática/imunologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Síndromes Paraneoplásicas/imunologia , Rombencéfalo/imunologia , Rombencéfalo/patologia , Tomografia Computadorizada por Raios XRESUMO
We report two cases of paraneoplastic limbic encephalitis (PLE) that differed in their clinical patterns, the underlying tumours, and the associated paraneoplastic antibodies. The first patient was a young adult male, with anti-MA-2 antibodies and testicular tumour. The clinical picture was restricted to limbic involvement. The second patient was a 56-year old, female heavy smoker; with seizures and depression, but also vertigo and diplopia. A low level of serum anti-Hu antibodies led to the detection of a small cell lung carcinoma by total body PET-scanning. In both cases, intrathecal synthesis of CSF oligoclonal IgG bands and of the corresponding paraneoplastic antibodies was demonstrated.
Assuntos
Encefalite Límbica/líquido cefalorraquidiano , Encefalite Límbica/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Animais , Feminino , Humanos , Encefalite Límbica/diagnóstico , Masculino , Pessoa de Meia-IdadeRESUMO
The association of an acute encephalopathy, neurosensory hearing loss and retinal branch artery occlusions in a 35 year old man as well as the absence of systemic disease suggest the diagnosis of Susac's syndrome. This is the eighth male case described, the syndrome being more frequently reported in females.
Assuntos
Perda Auditiva Neurossensorial/diagnóstico , Oclusão da Artéria Retiniana/diagnóstico , Vasculite do Sistema Nervoso Central/diagnóstico , Adulto , Cerebelo/patologia , Corpo Caloso/patologia , Angiofluoresceinografia , Seguimentos , Humanos , Masculino , Testes Neuropsicológicos , SíndromeRESUMO
The sigma 2 receptor subtype was studied in rat cerebral cortex and in C6 glioma cells homogenates using various compounds including class III antiarrhythmic drugs. The characteristics of (+)-[3H]-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-[3H]-3-PPP) binding were assessed in competition experiments with different displacers which revealed the presence of sigma 2 receptors. Various class III antiarrhythmic drugs inhibited (+)-[3H]-3-PPP binding with high affinity and their binding affinity was found to correlate with the potency of these compounds to increase the duration of action potentials measured in Purkinje fibers in electrophysiological studies. Since class III antiarrhythmic drugs are known to interact with voltage-dependent K+ channels, the present results provide evidence that the (+)-[3H]-3-PPP binding sites in rat brain possess the characteristics of K+ channels of class III antiarrhythmic drugs.