Interferon beta-1b is effective and has a favourable safety profile in Chinese patients with relapsing forms of multiple sclerosis

Abstract Background & Objective: No clinical study of any interferon beta therapy has yet been successfully conducted in Chinese multiple sclerosis patients, probably due to the low incidence of this disease in China. The primary objective of this study was to demonstrate that treating multiple sclerosis patients of Chinese origin with interferon beta-1b has a beneficial effect on disease course, as measured by the decrease of newly active lesions on magnetic resonance imaging. Methods: Chinese patients diagnosed with relapsing-remitting or secondary-progressive multiple sclerosis were enrolled in this multicenter, open label, single-arm study. Following a 3-month pre-treatment phase, patients were treated with 250 µg interferon beta-1b subcutaneously every other day for 6 months. Patients had regular assessments for treatment safety and efficacy of the treatment. Results: Thirty seven patients completed the trial. Significant decreases in the number of newly active lesions were observed in the 6-month treatment period compared with the pre-treatment period (median decrease 1.5 lesions, p<0.001). Most adverse events were mild and transient and no serious ones were observed. Conclusions: Treatment with interferon beta-1b significantly reduced the occurrence of new lesions and was well tolerated in this Chinese population. These findings support the use of interferon beta1b for treating Chinese MS patients

Rivastigmine Lowers Aβ and Increases sAPPα Levels, Which Parallel Elevated Synaptic Markers and Metabolic Activity in Degenerating Primary Rat Neurons

Overproduction of amyloid-β (Aβ) protein in the brain has been hypothesized as the primary toxic insult that, via numerous mechanisms, produces cognitive deficits in Alzheimer's disease (AD). Cholinesterase inhibition is a primary strategy for treatment of AD, and specific compounds of this class have previously been demonstrated to influence Aβ precursor protein (APP) processing and Aβ production. However, little information is available on the effects of rivastigmine, a dual acetylcholinesterase and butyrylcholinesterase inhibitor, on APP processing. As this drug is currently used to treat AD, characterization of its various activities is important to optimize its clinical utility. We have previously shown that rivastigmine can preserve or enhance neuronal and synaptic terminal markers in degenerating primary embryonic cerebrocortical cultures. Given previous reports on the effects of APP and Aβ on synapses, regulation of APP processing represents a plausible mechanism for the synaptic effects of rivastigmine. To test this hypothesis, we treated degenerating primary cultures with rivastigmine and measured secreted APP (sAPP) and Aβ. Rivastigmine treatment increased metabolic activity in these cultured cells, and elevated APP secretion. Analysis of the two major forms of APP secreted by these cultures, attributed to neurons or glia based on molecular weight showed that rivastigmine treatment significantly increased neuronal relative to glial secreted APP. Furthermore, rivastigmine treatment increased α-secretase cleaved sAPPα and decreased Aβ secretion, suggesting a therapeutic mechanism wherein rivastigmine alters the relative activities of the secretase pathways. Assessment of sAPP levels in rodent CSF following once daily rivastigmine administration for 21 days confirmed that elevated levels of APP in cell culture translated in vivo. Taken together, rivastigmine treatment enhances neuronal sAPP and shifts APP processing toward the α-secretase pathway in degenerating neuronal cultures, which mirrors the trend of synaptic proteins, and metabolic activity

Inter-intraspecific variation of chloroplast DNA of European Plantago spp

Inter- and intraspecific chloroplast DNA variation in four species of Plantago (P. lanceolata, P. major, P. media and P. coronopus) were analysed by comparing DNA fragment patterns produced by seven restriction endonucleases. Plant material was collected in seven European countries. Only 21.3 per cent of the 409 restriction sites were shared by all four species. Phylogenetic analysis, performed by constructing the most parsimonious trees, showed that genetic differentiation in cpDNA was very high among P. lanceolata, P. coronopus and the species pair P. media and P. major, which were more closely related. At the intraspecific level, four restricted site mutations were detected. Most of the variation was due to numerous small length mutations, one of which (70 bp) discriminated between the two subspecies of P. major (i.e. ssp. major and ssp. pleiosperma). This mutation was used successfully to show that, in Denmark, cpDNA introgression occurs from pleiosperma into major in the areas where the two subspecies grow together, whereas previous studies of the same subspecies in the Netherlands suggested introgression in the reverse direction. In P. lanceolata, five distinct types of cpDNA genome could be distinguished, one of these being widely distributed. Therefore, DNA variation was present both between and within populations. In P. media, three distinct cpDNA genomes were found, one being specific to diploid and tetraploid material from the Pyrenees, suggesting multiple origins of the autotetraploids in this species. Whereas cpDNA variation was observed in the two outcrossing species of Plantago (P. media and P. lanceolata) no variation was detected in the two autogamous subspecies of P. major. This suggests that chloroplast DNA variation may be related to nuclear genome diversity

Metabolic encephalopathies in Alzheimer disease

In 1906, German neuropathologist and psychiatrist Alois Alzheimer described eine eigenartige Erkrankung der Hirnrinde (a peculiar disease of the cerebral cortex). Alzheimer noted two abnormalities in autopsied brain tissue from his index case: senile plaques, proteinaceous structures previously described in the brain of normal elderly people; and abnormal cells delineated with silver stain that became known as neurofibrillary tangles (NFTs). The distribution and abundance of tangle-filled neurons are now the main criteria used to diagnose Alzheimer disease (AD) at autopsy