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Bone marrow Mesenchymal Stem Cells (BM-MSCs), due to their strong protective and anti-inflammatory abilities, have been widely investigated in the context of several diseases for their possible therapeutic role, based on the release of a highly proactive secretome composed of soluble factors and Extracellular Vesicles (EVs). BM-MSC-EVs, in particular, convey many of the beneficial features of parental cells, including direct and indirect &beta, amyloid degrading-activities, immunoregulatory and neurotrophic abilities. Therefore, EVs represent an extremely attractive tool for therapeutic purposes in neurodegenerative diseases, including Alzheimer&rsquo, s disease (AD). We examined the therapeutic potential of BM-MSC-EVs injected intracerebrally into the neocortex of APPswe/PS1dE9 AD mice at 3 and 5 months of age, a time window in which the cognitive behavioral phenotype is not yet detectable or has just started to appear. We demonstrate that BM-MSC-EVs are effective at reducing the A&beta, plaque burden and the amount of dystrophic neurites in both the cortex and hippocampus. The presence of Neprilysin on BM-MSC-EVs, opens the possibility of a direct &beta, amyloid degrading action. Our results indicate a potential role for BM-MSC-EVs already in the early stages of AD, suggesting the possibility of intervening before overt clinical manifestations.

Substantial data indicate that amyloid-? (A?), the major component of senile plaques, plays a central role in Alzheimer's Disease and indeed the assembly of naturally occurring amyloid peptides into cytotoxic aggregates is linked to the disease pathogenesis. Although A?42 is a highly aggregating form of A?, the co-occurrence of shorter A? peptides might affect the aggregation potential of the A? pool. In this study we aimed to assess whether the structural behavior of human A?42 peptide inside the brain is influenced by the concomitant presence of N-terminal fragments produced by the proteolytic activity of glial cells. We show that the occurrence of the human C-terminal truncated 1-24 A? fragment impairs A?42 clearance through blood brain barrier and promotes the formation of A?42 aggregates even in the healthy brain. By showing that A?1-24 has seeding properties for aggregate formation in intracranially injected wild type mice, our study provide the proof-of-concept that peptides produced upon A?42 cleavage by activated glial cells may cause phenotypic defects even in the absence of genetic mutations associated with Alzheimer's Disease, possibly contributing to the development of the sporadic form of the pathology.

Objective: To evaluate the safety and cost effectiveness of carotid surgery performed altering the perioperative protocol in an attempt to decrease resource utilisation. Setting: Department of vascular surgery in a large metropolitan teaching hospital in northern Italy. Design: Prospective, non-selective study. Materials and Methods: Three hundred and eighty carotid procedures were performed in 1995 on 343 patients (274 males, 69 females, mean age 68.2 years, range 47–86 years). The most important cost containment measures, were: (i) limiting the use of contrast arteriography to cases of dubious ultrasonographic diagnosis; (ii) routine use of loco-regional anaesthesia; (iii) postoperative admission to an intensive care unit (ICU) only in selected cases; (iv) early postoperative discharge where possible. Results: Mortality was 0.26% and neurological morbidity 1.58%. General anaesthesia was required in eight patients (2.1%), and only seven patients (1.8%) were admitted postoperatively to the ICU. Arteriography was performed in 56 cases (14.7%). The average hospital stay was 5 days with a global cost of 43 036 ECU, as compared with a cost of 6764 ECU for patients treated traditionally with routine arteriography, general anaesthesia and routine ICU admission. Conclusions: Selective use of arteriography and ICU, routine use of loco-regional anaesthesia and reduced hospital stay make it possible to lower the cost of cartid surgery without sacrificing quality.