Inhibition of platelet aggregation by carbon monoxide-releasing molecules (CO-RMs): comparison with NO donors

Carbon monoxide (CO) and CO-releasing molecules (CO-RMs) inhibit platelet aggregation in vitro. Herein, we compare the anti-platelet action of CORM-3, which releases CO rapidly (t½ 1 min), and CORM-A1, which slowly releases CO (t½ = 21 min). The anti-platelet effects of NO donors with various kinetics of NO release were studied for comparison. The effects of CO-RMs and NO donors were analyzed in washed human platelets (WP), platelets rich plasma (PRP), or whole blood (WB) using aggregometry technique. CORM-3 and CORM-A1 inhibited platelet aggregation in human PRP, WP, or WB, in a concentration-dependent manner. In all three preparations, CORM-A1 was more potent than CORM-3. Inhibition of platelets aggregation by CORM-A1 was not significantly affected by a guanylate cyclase inhibitor (ODQ) and a phosphodiesterase-5 inhibitor, sildenafil. In contrast, inhibition of platelet aggregation by NO donors was more potent with a fast NO releaser (DEA-NO, t½ = 2 min) than slow NO releasers such as PAPA-NO (t½ = 15 min) or other slow NO donors. Predictably, the anti-platelet effect of DEA-NO and other NO donors was reversed by ODQ while potentiated by sildenafil. In contrast to NO donors which inhibit platelets proportionally to the kinetics of NO released via activation of soluble guanylate cyclase (sGC), the slow CO-releaser CORM-A1 is a superior anti-platelet agent as compared to CORM-3 which releases CO instantly. The anti-platelet action of CO-RMs does not involve sGC activation. Importantly, CORM-A1 or its derivatives representing the class of slow CO releasers display promising pharmacological profile as anti-platelet agents

Dopamine Transporter SPECT Imaging in Corticobasal Syndrome

evidence of preserved nigral neuronal density. imaging evidence of preserved nigral terminals have been recently described.In this multicenter study, we investigated presynaptic nigrostriatal function in 36 outpatients fulfilling clinical criteria for “probable corticobasal degeneration” (age 71±7.3 years; disease duration 3.9±1.6 years), 37 PD and 24 healthy control subjects using FP-CIT single photon emission computed tomography. Clinical, neuropsychological, and magnetic resonance imaging assessment was performed to characterize CBS patients. Linear discriminant analysis was used to categorize normal vs. pathological scans.FP-CIT binding reduction in patients with CBS was characterized by larger variability, more uniform reduction throughout the striatum and greater hemispheric asymmetry compared to PD. Moreover, there was no significant correlation between tracer uptake values and clinical features such as disease duration and severity. Despite all CBS subjects showed obvious bilateral extrapyramidal signs, FP-CIT uptake was found to be normal bilaterally in four CBS patients and only unilaterally in other four cases. Extensive clinical, neuropsychological and imaging assessment did not reveal remarkable differences between CBS subjects with normal vs. pathological FP-CIT uptake.Our findings support the hypothesis that extrapyramidal motor symptoms in CBS are not invariably associated with SNc neuronal degeneration and that supranigral factors may play a major role in several cases. CBS individuals with normal FP-CIT uptake do not show any clinical or cognitive feature suggesting a different pathology than CBD

Localisation in PET images: direct fitting of the intercommissural (AC-PC) line.

A technique is described for estimating the position of the intercommisural line (AC-PC line) directly from landmarks on positron emission tomographic (PET) images, namely the ventral aspects of the anterior and posterior corpus callosum, the thalamus, and occipital pole. The relationship of this estimate to the true AC-PC line, fitted through the centres of the anterior and posterior commissures, showed minimal vertical and angular displacement when measured on magnetic resonance imaging (MRI) scans. Using regression analysis, the ease and reliability of fitting to these points was found to be high. This directly derived AC-PC line estimate was validated in terms of the assumptions used in the method of Fox et al. The ratio of distance between the AC-PC line and a line passing through the base of the inion (GI line) to total brain height was 0.21, as predicted. The technique has been further validated by localizing focal activation of the sensorimotor cortex. The technique is discussed in terms of absolute limits to localization of structures in the brain using noninvasive tomographic techniques in general and PET in particular

Functional magnetic resonance imaging of single motor events reveals human presupplementary motor area.

Conventional functional imaging paradigms use periods of repetitive task performance to generate sustained functional signal changes. We have developed a technique of imaging the small, transient signal changes that occur after single cognitive events. The technique uses echo-planar imaging at 3 T to generate functional images of the whole brain with a temporal resolution of 3 seconds. It uses a signal averaging technique to create time sweeps of functional activity. After a single cognitive event, widely distributed patterns of brain activation can be detected and their time course measured. This technique enables the individual cognitive tasks that constitute a paradigm to be analyzed separately and compared. We describe the application of this new technique to separate the cognitive elements in a simple "go/no-go" motor paradigm. Comparison of activation patterns during "go" and "no-go" responses reveals hierarchical subdivision of the medial premotor cortex into an anterior region (presupplementary motor area) involved in movement decision making and a posterior region (supplementary motor area proper) directly involved in motor execution

Avaliação da doença de Parkinson pela ressonância magnética Evaluation of Parkinson´s disease using magnetic resonance imaging

OBJETIVO: Avaliar a doença de Parkinson pela ressonância magnética. MATERIAIS E MÉTODOS: De outubro de 1999 a outubro de 2002, foram estudados 42 pacientes com parkinsonismo, por meio de um aparelho de ressonância magnética de 1,5 T. Os pacientes foram divididos em dois grupos: grupo com doença de Parkinson (n = 26) e grupo com síndrome parkinsoniana atípica (n = 16), sendo os resultados comparados com um grupo controle (n = 18). Foram avaliadas as seguintes variáveis: espessura da pars compacta do mesencéfalo, grau de hipointensidade de sinal no putâmen, grau de atrofia cerebral, lesões no mesencéfalo, lesões na substância branca e a presença de lesão na borda póstero-lateral do putâmen. A análise estatística dos dados foi realizada, com a utilização do programa SPSS. RESULTADOS: A média de idade foi de 58,2 anos nos grupos com doença de Parkinson e controle, e 60,5 anos no grupo com síndrome parkinsoniana atípica. Os pacientes com doença de Parkinson e síndrome parkinsoniana atípica apresentaram redução da espessura da pars compacta e maior grau de hipointensidade de sinal no putâmen. O grau de atrofia cerebral foi maior nos pacientes com síndrome parkinsoniana atípica. As lesões no mesencéfalo e na substância branca foram semelhantes entre os grupos. O sinal hiperintenso na borda póstero-lateral do putâmen foi um achado pouco freqüente na população estudada, mas sugestivo de atrofia de múltiplos sistemas. CONCLUSÃO: Desta forma, a ressonância magnética detectou alterações morfológicas cerebrais que podem auxiliar no diagnóstico por imagem das síndromes parkinsonianas.<br>OBJECTIVE: The objective of this study was to evaluate the magnetic resonance imaging findings in patients with Parkinson's disease. MATERIALS AND METHODS: In the period from October 1999 to October 2002, 42 patients with parkinsonism were investigated using a 1.5 T MR equipment. Patients were divided into two groups: patients with Parkinson's disease (n = 26) and patients with atypical Parkinsonian syndrome (n = 16). The results were compared with a control group (n = 18). The following variables were evaluated: thickness of the mesencephalon compact pars, hypointense signal in the putamen, degree of brain atrophy, lesions in the mesencephalon, lesions in the white matter, and the presence of lesions in the posterior-lateral edge of the putamen. Statistical data analysis was carried out using the SPSS program. RESULTS: The mean age was 58.2 years for the Parkinson's disease and control groups, and 60.5 years for the atypical Parkinsonian syndrome group. Patients with Parkinson's disease and atypical Parkinsonian syndromes presented decreased thickness of the compact pars and a higher degree of signal hypointensity in the putamen. Cerebral atrophy was more prominent in the patients with atypical Parkinsonian syndrome. Lesions in mesencephalon and white matter were similar in both groups. The frequency of hyperintense signal in the posterior-lateral edge of the putamen was low within the studied population, although that could suggest multiple-system atrophy. CONCLUSION: Magnetic resonance imaging allows the detection of brain morphological changes that may help in the diagnosis of Parkinsonian syndromes