RESUMO
Neuropathological hallmarks of Alzheimer's disease (AD) are amyloid plaques and neurofibrillary tangles, containing betaA(42) peptide and tau protein, respectively. Amyloid plaques contain also glycosaminoglycans (GAGs). Whereas cerebrospinal fluid (CSF) levels of betaA(42) peptide and tau protein have been demonstrated as potential markers of Alzheimer's disease (AD), no data are available for GAGs. We determined (Elisa) tau and betaA(42) CSF levels, as well as serum antibodies to GAGs in 9 AD patients, and the values were analyzed in relation to age and severity of the disease. Beta-A42 and tau CSF levels were significantly reduced and increased, respectively, in AD patients when compared to controls, but they did not correlate with the severity of the disease. Despite their role in amyloidogenesis, we did not find evidence for the use of GAGs as diagnostic marker of AD.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Anticorpos/sangue , Encéfalo/metabolismo , Glicosaminoglicanos/imunologia , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/patologia , Encéfalo/imunologia , Progressão da Doença , Glicosaminoglicanos/metabolismo , Humanos , Pessoa de Meia-Idade , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Placa Amiloide/metabolismo , Placa Amiloide/patologiaRESUMO
A 24-year-old male, who suffered since childhood from a progressive form of ataxia associated with peripheral neuropathy, was found severely deficient in serum vitamin E. He walked with bilateral aid and presented severe dysmetria of the limbs and dysarthric speech; muscular strength and trophism were slightly diminished in the distal muscles of four limbs and there was hypotonia of the arms; he presented absent deep tendon reflexes, bilateral Babinski's sign, reduced proprioception at four limbs, pes cavus and fasciculations of the tongue. Intestinal fat malabsorption and other gastrointestinal or haematological conditions associated with deficiency of this vitamin were ruled out. In this patient, after 2 years of a daily supplement of high doses of vitamin E, a further progression of the disease was not observed and, moreover, the neurophysiological characteristics of his neuropathy appeared clearly improved. A longitudinal evaluation of serum vitamin E levels showed values in the normal range after 13 months of therapy. The patient had molecular genetic analysis of chromosome 8 and was found homozygous for the unusual mutation 513insTT in the alpha-tocopherol transfer protein gene.
Assuntos
Ataxia/tratamento farmacológico , Doença de Refsum/tratamento farmacológico , Deficiência de Vitamina E/tratamento farmacológico , Administração Oral , Adulto , Ataxia/fisiopatologia , Ataxia/prevenção & controle , Suplementos Nutricionais , Humanos , Masculino , Doença de Refsum/fisiopatologia , Doença de Refsum/prevenção & controle , Vitamina E/uso terapêutico , Deficiência de Vitamina E/genética , Deficiência de Vitamina E/fisiopatologiaAssuntos
Anticorpos Anticardiolipina/imunologia , Doenças Autoimunes/complicações , Imunoglobulina G/imunologia , Deficiência de Proteína S/complicações , Trombose dos Seios Intracranianos/etiologia , Tromboflebite/etiologia , Doença Aguda , Adulto , Doenças Autoimunes/imunologia , Feminino , Humanos , Deficiência de Proteína S/imunologiaAssuntos
Glicemia/metabolismo , Encéfalo/efeitos dos fármacos , Antagonistas dos Receptores de Dopamina D2 , Dopamina/fisiologia , Levodopa/farmacologia , Receptores de Dopamina D1/antagonistas & inibidores , Animais , Benzazepinas/farmacologia , Encéfalo/fisiologia , Mapeamento Encefálico , Desoxiglucose/metabolismo , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Masculino , Ratos , Ratos Endogâmicos F344 , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Comportamento Estereotipado/efeitos dos fármacos , Comportamento Estereotipado/fisiologia , Sulpirida/farmacologiaRESUMO
The time course and the relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male adult Fischer-344 rats after administration of quipazine, a serotonin 5-HT2-3 receptor agonist. rCMRglc was determined, using the quantitative autoradiographic [14C]deoxyglucose technique, in 92 brain regions at 30, 60, 90 and 120 min after quipazine 20 mg/kg i.p. and at 60 min after quipazine 5 mg/kg i.p. Peak metabolic effects were observed 60 min after quipazine 20 mg/kg i.p. when rCMRglc was significantly elevated in 27 (29%) brain regions (mean rise 17%). Quipazine increased rCMRglc in brain regions with high densities of 5-HT3 receptors (area postrema, olfactory tubercle, amygdala), in dopaminergic nuclei (substantia nigra pars compacta and pars reticulata) and terminal fields of their projections (zona incerta, subthalamic nucleus, preoptic magnocellular area, nucleus of facial nerve). The topographic distribution and direction of rCMRglc changes induced by quipazine are different from those produced by the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and, consistent with the pharmacological and binding properties of quipazine, suggest a preferential activation of 5-HT3 receptors.
Assuntos
Química Encefálica/efeitos dos fármacos , Quipazina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Anfetaminas/farmacologia , Animais , Autorradiografia , Gasometria , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Encéfalo/anatomia & histologia , Desoxiglucose , Relação Dose-Resposta a Droga , Glucose/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos F344 , Fatores de TempoRESUMO
The autoradiographic 14C-2-deoxy-D-glucose method was used to determine local cerebral glucose utilization (LCGU) during propofol anesthesia and recovery in 52 regions of the rat brain. Control rats intravenously received 5 ml.kg-1.h-1 of the egg-oil-glycerol emulsion that constitutes the vehicle for propofol. Anesthetized animals received an iv bolus of propofol (20 mg/kg) followed by continuous infusion of the anesthetic at 12.5, 25, or 50 mg.kg-1.h-1 for 1 h prior to injection of 14C-2-deoxy-D-glucose and for the following 45 min. In addition, a fifth group of animals were studied immediately after awakening from a 20 mg/kg bolus of propofol as indicated by the first reappearance of head lift. All rats were spontaneously breathing room air throughout the experimental procedure. The general pattern of the cerebral metabolic response to propofol anesthesia was a dose-related, widespread depression of LCGU. At the three infusion rates of propofol tested, overall mean LCGU was reduced by 33%, 49%, and 55%, respectively, and significant decreases were observed in 60%, 85%, and 90% of the regions assayed. These effects were rapidly reversible, since in the recovery group, LCGU returned to near control values in the majority of the brain areas. Although all of the anatomofunctional systems (sensorimotor, extrapyramidal, limbic, and reticular) were involved, forebrain structures showed a greater sensitivity to the depressant action of propofol than did hindbrain regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anestesia Intravenosa , Encéfalo/metabolismo , Glucose/metabolismo , Propofol , Animais , Encéfalo/efeitos dos fármacos , Depressão Química , Masculino , Ratos , Ratos Endogâmicos F344RESUMO
The time course and relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) and of motor behavior were measured in awake male adult Fischer-344 rats after administration of meta-chlorophenylpiperazine (MCPP), a serotonin-1B receptor agonist. rCMRglc was determined, using the quantitative autoradiographic [14C]deoxyglucose technique, in 71 brain regions at 5, 15, 30 and 60 min after administration of MCPP 2.5 mg/kg i.p., and at 15 min after MCPP 25 and 40 mg/kg. The time course of performance on a rotating rod was measured periodically for 60 min after MCPP 2.5 mg/kg, a dose which impaired locomotion and reduced rCMRglc maximally at 15-30 min after its administration. At 15 min, rCMRglc declined significantly in 28 (40%) of the areas studied (mean decline 16%). Most regions affected were telencephalic or diencephalic, corresponding to the projection areas of serotonergic fibers arising from the raphe nuclei. After higher doses of MCPP, a behavioral serotonin syndrome was observed with both rCMRglc increases and decreases (25 mg/kg) or only rCMRglc increases (40 mg/kg). Whereas behavioral and metabolic activation induced by high doses of MCPP may result from stimulation at postsynaptic serotonin receptors, rCMRglc reductions and hypomotility produced by MCPP 2.5 mg/kg resemble the effects of serotonin receptor antagonists and suggest that, at this low dose, MCPP acts at modulatory serotonin autoreceptors to reduce endogenous serotonin release.
Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Desoxiaçúcares/farmacocinética , Desoxiglucose/farmacocinética , Glicolatos/farmacologia , Atividade Motora/efeitos dos fármacos , Piperazinas/farmacologia , Receptores de Serotonina/fisiologia , Animais , Encéfalo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Endogâmicos F344 , Receptores de Serotonina/efeitos dos fármacosRESUMO
A vascular malformation, consisting of a venous vessel bridgeing the right inferior petrosal sinus and the anterior spinal veins, was found in the posterior fossa. The vessel presented a ring-like course around the right trigeminal root, and it was parallel and dorsal to the basilar artery. The malformation was associated with cutaneous and hepatic angiomas and peri-osteal lipomas. It had been clinically silent for 52 years, when it thrombosed causing death. The authors think that, within a general mesenchymopatic state, this is a result of the persistence of an embryonal cerebral venous pattern.
Assuntos
Artéria Basilar/anormalidades , Veias Cerebrais/anormalidades , Síndrome da Persistência do Padrão de Circulação Fetal/diagnóstico , Autopsia , Artéria Basilar/patologia , Veias Cerebrais/patologia , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Síndrome da Persistência do Padrão de Circulação Fetal/patologia , Trombose/etiologia , Trombose/patologiaRESUMO
Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic [14C]2-deoxy-D-glucose method, in 92 discrete brain regions of awake rats, at 1, 2, 3, or 4 h after administration of the serotonergic antagonist methiothepin 0.1 mg/kg IP. The drug produced a cataleptic behavior that peaked in intensity at 3 h after its administration. LCGU declined significantly in 35% of the 92 regions at one or more time points after methiothepin administration. No area of increased metabolism was found. The time-course of the decline in LCGU closely paralleled the intensity of catalepsy; the peak effect was at 3 h, when LCGU was significantly reduced in 32% of the regions examined (mean decline for all regions was 15%). Metabolic depression after methiothepin was most notable in the forebrain, where LCGU declined in many regions of the cerebral cortex, basal ganglia, and thalamus. Most of the regions affected by methiothepin possess a substantial number of serotonin receptors, although LCGU was also reduced in a few regions not primarily involved in serotonergic neurotransmission.
Assuntos
Encéfalo/metabolismo , Dibenzotiepinas/farmacologia , Glucose/metabolismo , Metiotepina/farmacologia , Animais , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344RESUMO
Blood viscosity indices, fibrinolytic activity and other serum proteins related to haemocoagulation have been studied in 36 patients with multiple sclerosis. The whole blood viscosity was found to be increased in multiple sclerosis. The increase was caused by a decrease in erythrocyte deformability since plasma viscosity and haematocrit were normal. Plasminogen, fibrinogen and alpha 2 antitrypsin levels were found to be lower than normal. Such alterations were not observed in a group of patients with other non-immunological neurological diseases. In the latter group some coagulation indices were even higher than normal. The higher mean age of the pathological controls could explain the observed levels. The abnormalities observed in multiple sclerosis patients are considered to be a consequence of a non-specific activation of the coagulative system in a chronic immunological disease.