Platelet activation was significantly increased in acute ischemic stroke and substantially decreased thereafter. The lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel raises the prospect of the need for more effective antiplatelet agents or a synergistic combination therapy for stroke prevention in the future.
The deposition of amyloid-beta (Abeta) contributes to the pathogenesis of Alzheimer's disease. Even at low levels, Abeta may interfere with various signaling cascades critical for the synaptic plasticity that underlies learning and memory. Brain-derived neurotrophic factor (BDNF) is well known to be capable of inducing the synthesis of activity-regulated cytoskeleton-associated protein (Arc), which plays a fundamental role in modulating synaptic plasticity. Our recent study has demonstrated that treatment of fibrillar Abeta at a nonlethal level was sufficient to impair BDNF-induced Arc expression in cultured rat cortical neurons. In this study, BDNF treatment alone induced the activation of the phosphatidylinositol 3-kinase-Akt-mammlian target of rapamycin (PI3K-Akt-mTOR) signaling pathway, the phosphorylation of eukaryotic initiation factor 4E binding protein (4EBP1) and p70 ribosomal S6 kinase (p70S6K), the dephosphorylation of eukaryotic elongation factor 2 (eEF2), and the expression of Arc. Interrupting the PI3K-Akt-mTOR signaling pathway by inhibitors prevented the effects of BDNF, indicating the involvement of this pathway in BDNF-induced 4EBP1 phosphorylation, p70S6K phosphorylation, eEF2 dephosphorylation, and Arc expression. Nonlethal Abeta pretreatment partially blocked these effects of BDNF. Double- immunofluorescent staining in rat cortical neurons further confirmed the coexistence of eEF2 dephosphorylation and Arc expression following BDNF treatment regardless of the presence of Abeta. These results reveal that, in cultured rat cortical neurons, Abeta interrupts the PI3K-Akt-mTOR signaling pathway that could be involved in BDNF-induced Arc expression. Moreover, this study also provides the first evidence that there is a close correlation between BDNF-induced eEF2 dephosphorylation and BDNF-induced Arc expression. (c) 2009 Wiley-Liss, Inc.
Muscular dystrophy (MD) comprises a group of diseases characterized by progressive muscle weakness that induces functional deterioration. Clinical management requires the use of a well-designed scale to measure patients' functional status. This study aimed to investigate the quality of the functional scales used to assess patients with different types of MD. The Brooke scale and the Vignos scale were used to grade arm and leg function, respectively. The Barthel Index was used to evaluate the function of daily living activity. We performed tests to assess the acceptability of these scales. The characteristics of the different types of MD are discussed. This was a multicenter study and included patients diagnosed with Duchenne muscular dystrophy (DMD) (classified as severely progressive MD), Becker muscular dystrophy (BMD), limb girdle muscular dystrophy (LGMD) and facioscapulohumeral muscular dystrophy (FSHD). BMD, LGMD, and FSHD were classified as slowly progressive MD. The results demonstrated that the Brooke scale was acceptable for grading arm function in DMD, but was unable to discriminate between differing levels of severity in slowly progressive MD. The floor effect was large for all types of slowly progressive MD (range, 20.0-61.9), and was especially high for BMD. The floor effect was also large for BMD (23.8%) and FSHD (50.0%) using the Vignos scale. Grades 6-8 of the Vignos scale were inapplicable because they included items involving the use of long leg braces for walking or standing, and some patients did not use long leg braces. In the Barthel Index, a ceiling effect was prominent for slowly progressive MD (58.9%), while a floor effect existed for DMD (17.9%). Among the slowly progressive MDs, FSHD patients had the best level of functioning; they had better leg function and their daily living activities were less affected than patients with other forms of slowly progressive MD. The results of this study demonstrate the acceptability of the different applications used for measuring functional status in patients with different types of MD. Some of the limitations of these measures as applied to MD should be carefully considered, especially in patients with slowly progressive MD. We suggest that these applications be used in combination with other measures, or that a complicated instrument capable of evaluating the various levels of functional status be used.
115Background: White matter damage is common after carbon monoxide (CO) intoxication, but in vivo follow-up studies about the mechanism of white matter damage are not possible in pathology series. Diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) can quantify diffusion parameters and volumetric changes in white matter that can be correlated with neuropsychological performances in longitudinal studies. Methods: We examined 9 patients with CO intoxication using DTI, VBM and neuropsychologic tests at an average of 3 and 10 months after CO exposure. We used data from 18 age-and sex-matched controls for comparison. Results: We found that cognitive recovery at 10 months after CO intoxication was not significant, although it was after 3 months. The neuropsychologic tests correlated better for the fibre tract of the semicentrum ovale and not the periventricular fibres. Diffusion measures suggest increases in fractional anisotropy, mean diffusivity and axial eigenvalues over time, while increases in radial eigenvalue were evident at 3 months compared with controls. Periventricular white matter atrophy was observed 10 months after CO intoxication. Limitations: Our study included few cases, and the interpretation of the putative changes on neuroimaging findings cannot be confirmed by histology. Conclusion: Our study showed that the evolution of white matter injury in CO encephalopathy occurred over time. Cognitive recovery was not evident in the follow-up period because of white matter injuries.
The SARS outbreak adversely affected seizure control because of AED withdrawal. Patients with polytherapy, non-seizure free and symptomatic etiologies were more susceptible to recurrence of seizures after AED withdrawal.
This study was conducted to investigate the influence of high-frequency aircraft noise on the function of the auditory system of school-age children. A total of 228 students attending a school near an airport (school A) and 151 students attending a school far from an airport (school B) were analyzed. Audiometry and brainstem auditory evoked potential (BAEP) detection were performed in all subjects to evaluate cochlear and retrocochlear function. The results of audiometry indicated that hearing ability was significantly worse in the children of school A, which was located under the flight paths. The values of pure tone average, high pure tone average, and threshold at 4 kHz were all higher in children who were frequently exposed to aircraft noise. There was no consistent difference in BAEP latencies between the two schools. These results indicate that central transmission is not affected in children who have been exposed to aircraft noise for several years. The results of the present study showed a significant association between aircraft noise exposure and prevalence of noise-induced hearing loss. Although damage to peripheral cochlear organs was confirmed in school-age children, involvement of the central auditory pathway could not be verified.
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