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31.
The role of cognitive reserve on terminal decline: a cross‐cohort analysis from two European studies: OCTO‐Twin,Sweden, and Newcastle 85+, UK 下载免费PDF全文
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Nicolina Cristina Sorrentino Veronica Maffia Sandra Strollo Vincenzo Cacace Noemi Romagnoli Anna Manfredi Domenico Ventrella Francesco Dondi Francesca Barone Massimo Giunti Anne-Renee Graham Yan Huang Susan L Kalled Alberto Auricchio Maria Laura Bacci Enrico Maria Surace Alessandro Fraldi 《Molecular therapy》2016,24(2):276-286
Cerebrospinal fluid administration of recombinant adeno-associated viral (rAAV) vectors has been demonstrated to be effective in delivering therapeutic genes to the central nervous system (CNS) in different disease animal models. However, a quantitative and qualitative analysis of transduction patterns of the most promising rAAV serotypes for brain targeting in large animal models is missing. Here, we characterize distribution, transduction efficiency, and cellular targeting of rAAV serotypes 1, 2, 5, 7, 9, rh.10, rh.39, and rh.43 delivered into the cisterna magna of wild-type pigs. rAAV9 showed the highest transduction efficiency and the widest distribution capability among the vectors tested. Moreover, rAAV9 robustly transduced both glia and neurons, including the motor neurons of the spinal cord. Relevant cell transduction specificity of the glia was observed after rAAV1 and rAAV7 delivery. rAAV7 also displayed a specific tropism to Purkinje cells. Evaluation of biochemical and hematological markers suggested that all rAAV serotypes tested were well tolerated. This study provides a comprehensive CNS transduction map in a useful preclinical large animal model enabling the selection of potentially clinically transferable rAAV serotypes based on disease specificity. Therefore, our data are instrumental for the clinical evaluation of these rAAV vectors in human neurodegenerative diseases. 相似文献
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Coppola N Tonziello G Pisaturo M Messina V Guastafierro S Fiore M Iodice V Sagnelli C Stanzione M Capoluongo N Pasquale G Sagnelli E 《Journal of medical virology》2011,83(11):1909-1916
The aim of the study was to evaluate clinical and virological differences in HBV reactivation between patients with overt and occult HBV infection. Twenty-three consecutive patients with symptomatic HBV reactivation occurring during or after immunosuppressive therapy were enrolled in a retrospective study: 10 with reactivation of overt HBV infection (overt group) and 13 of occult HBV infection (occult group). Twenty-one patients were treated with nucleot(s)ide analogues after HBV reactivation. Regimens including rituximab or fludarabine were administered more frequently in the occult group (61% vs. 31%, respectively). HBV reactivation was severe frequently in the overt (40%) and occult groups (38.4%). Patients in the overt group showed higher HBV-DNA titers (1.1 × 10(8) ± 1.4 × 10(8) vs. 5.1 × 10(5) ± 6.8 × 10(5) IU; P < 0.005). Seven patients died during HBV reactivation, two in the overt and five in the occult group. Of these seven patients, two remained untreated and five had been treated with Lamivudine; of the 16 patients showing remission of HBV reactivation, four had been treated with Lamivudine, four with Entecavir, two with Telbivudine, and six with Lamivudine plus Adefovir. It is concluded that HBV reactivation is life-threatening in patients with diseases inhibiting the immune response and/or receiving immunosuppressive drugs. Supportive therapy without antiviral drugs or Lamivudine monotherapy may not be effective for treating patients with HBV reactivation. 相似文献
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Timofte D Dandrieux J Wattret A Fick J Williams NJ 《Journal of clinical microbiology》2011,49(9):3411-3414
This is the first report of Escherichia coli isolates producing CTX-M-15, the predominant type of extended-spectrum β-lactamase (ESBL) associated with clinical disease in humans in the United Kingdom, in a United Kingdom pet dog. This report also describes the first isolation of CTX-M/Tem ESBL-positive E. coli from bile in dogs with hepatobiliary disease. 相似文献
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Establishing long-term cultures with self-renewing acute myeloid leukemia stem/progenitor cells 总被引:1,自引:0,他引:1
van Gosliga D Schepers H Rizo A van der Kolk D Vellenga E Schuringa JJ 《Experimental hematology》2007,35(10):1538-1549
OBJECTIVE: With the emergence of the concept of the leukemia stem cell, assays to study them remain pivotal in understanding (leukemic) stem cell biology. METHODS: We have cultured acute myeloid leukemia CD34(+) cells on bone marrow stroma. Long-term expansion was monitored and self-renewal was addressed by replating of Leukemic-cobblestone area-forming cells (L-CAs). Also, lentiviral vectors were generated that could target L-CAs. RESULTS: A strong expansion was observed in about 75% of the acute myeloid leukemia cases (n = 30) and long-term cultures could be maintained for up to 24 weeks on MS5 bone marrow stromal cells. Cells that were able to initiate leukemic cobblestone areas resided in the CD34(+) population and were absent from the CD34(-) population. Self-renewal within these L-CAs was determined by sequential passaging of these L-CAs onto new MS5 stromal layers, which resulted in the generation of second, third, and fourth L-CAs, which were able to sustain long-term expansion and generated high numbers of immature undifferentiated suspension cells. CD34(+) cells that were able to initiate long-term cultures all coexpressed MEIS1 and HOXA9, and expressed elevated BMI1 levels. CONCLUSION: We present a novel long-term leukemic stem/progenitor assay in which new drugs can be tested and in which genes can be overexpressed or downmodulated using a lentiviral approach in order to obtain more insight into the process of leukemic transformation and self-renewal. 相似文献
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Guido Altissimi Luigi Gallucci Lidia Prattichizzo Dorina Arcamone Carla Monacelli 《The Laryngoscope》1994,104(3):325-328
This study reports variations observed under general anesthesia through small-bore endotracheal tubes in Po2, Pco2, Hco3, percentage saturation of O2, and pH levels in 39 patients who underwent laryngeal microsurgery lasting from 10 to 100 minutes. The tendency to an increase in Pco2 levels reached statistical significance only at the 100th minute but did not constitute a risk for patients as values remained within the limits of “permitted hypercapnia.” Po2, percentage saturation of oxygen, and Hco3 levels did not vary significantly. pH values tended to fall (respiratory acidosis) in correlation to the increase in Pco2. Small-bore endotracheal tubes can safely be used for laryngeal microsurgery when operating times are not longer than 100 minutes. 相似文献
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Freitas MS Romano-Lieber NS 《Cadernos de saúde pública / Ministério da Saúde, Funda??o Oswaldo Cruz, Escola Nacional de Saúde Pública》2007,23(1):167-175
The development of new drugs and limitations of clinical trials have increased the likelihood of adverse drug events. Pharmacovigilance is essential to detect and evaluate adverse drug events, thereby reducing risks and avoiding excessive public health costs. This study focused on the pharmacovigilance programs in the pharmaceutical industry in S?o Paulo State, Brazil. Data were collected through questionnaires sent electronically to 105 companies, 41.9% of which responded. The main reason for implementing pharmacovigilance programs was to comply with legal requirements, while the main justification for its absence was production limited to herbal remedies, officinal products, and supplements. The article discusses the obstacles to program implementation, resources used, and characteristics of several such programs. Conclusions: (a) standardization is the reason for the increasing number of programs and reports, but more specific guidelines are needed; (b) results depend on multi-sector involvement; (c) customer service centers are an important source of reports; and (d) operation of the service requires only modest human and material resources. 相似文献