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991.
Marino M. Bianchin Tonicarlo R. Velasco Erica R. Coimbra Ana C. Gargaro Sara R. Escorsi-Rosset Lauro Wichert-Ana Vera C. Terra Veriano Alexandre Jr David Araujo Jr Antonio Carlos dos Santos Regina M. F. Fernandes Jo?o A. Assirati Jr Carlos G. Carlotti Jr Jo?o P. Leite Osvaldo M. Takayanagui Hans J. Markowitsch Américo C. Sakamoto 《PloS one》2013,8(4)
Background
Where neurocysticercosis (NCC) is endemic, chronic calcified neurocysticercosis (cNCC) can be observed in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). Considering that both disorders cause recurrent seizures or cognitive impairment, we evaluated if temporal lobectomy is cognitively safe and effective for seizure control in MTLE-HS plus cNCC.Methods
Retrospective cohort study of neuropsychological profile and surgical outcome of 324 MTLE-HS patients submitted to temporal lobectomy, comparing the results according to the presence or absence of cNCC.Findings
cNCC occurred in 126 (38.9%) of our MTLE-HS patients, a frequency higher than expected, more frequently in women than in men (O.R. = 1.66; 95% C.I. = 1.05–2.61; p = 0.03). Left-side (but not right side) surgery caused impairment in selected neuropsychological tests, but this impairment was not accentuated by the presence of cNCC. Ninety-four (74.6%) patients with MTLE-HS plus cNCC and 153 patients (77.3%) with MTLE-HS alone were Engel class I after surgery (O.R. = 1.16; 95% C.I. = 0.69–1.95; p = 0.58). However, the chances of Engel class IA were significantly lower in MTLE-HS plus cNCC than in patients with MTLE-HS alone (31.7% versus 48.5%; O.R. = 2.02; 95% C.I. = 1.27–3.23; p = 0.003). Patients with MTLE-HS plus cNCC showed higher rates of Engel class ID (15.1% versus 6.6%; O.R. = 2.50; 95% C.I. = 1.20–5.32; p = 0.012).Interpretation
cNCC can be highly prevalent among MTLE-HS patients living in areas where neurocysticercosis is endemic, suggesting a cause-effect relationship between the two diseases. cNCC does not add further risk for cognitive decline after surgery in MTLE-HS patients. The rates of Engel class I outcome were very similar for the two groups; however, MTLE-HS plus cNCC patients achieved Engel IA status less frequently, and Engel ID status more frequently. Temporal lobectomy can be safely performed in most patients with MTLE-HS plus cNCC without affecting cognitive outcome. Long-term surgical seizure control in MTLE-HS plus cNCC is still satisfactory, as long as selected patients remain under medication. 相似文献992.
Mara R. N. Celes Lygia M. Malvestio Sylvia O. Suadicani Cibele M. Prado Maria J. Figueiredo Erica C. Campos Ana C. S. Freitas David C. Spray Herbert B. Tanowitz Jo?o S. da Silva Marcos A. Rossi 《PloS one》2013,8(7)
Sepsis, a major cause of morbidity/mortality in intensive care units worldwide, is commonly associated with cardiac dysfunction, which worsens the prognosis dramatically for patients. Although in recent years the concept of septic cardiomyopathy has evolved, the importance of myocardial structural alterations in sepsis has not been fully explored. This study offers novel and mechanistic data to clarify subcellular events that occur in the pathogenesis of septic cardiomyopathy and myocardial dysfunction in severe sepsis. Cultured neonatal mice cardiomyocytes subjected to serum obtained from mice with severe sepsis presented striking increment of [Ca2+]i and calpain-1 levels associated with decreased expression of dystrophin and disruption and derangement of F-actin filaments and cytoplasmic bleb formation. Severe sepsis induced in mice led to an increased expression of calpain-1 in cardiomyocytes. Moreover, decreased myocardial amounts of dystrophin, sarcomeric actin, and myosin heavy chain were observed in septic hearts associated with depressed cardiac contractile dysfunction and a very low survival rate. Actin and myosin from the sarcomere are first disassembled by calpain and then ubiquitinated and degraded by proteasome or sequestered inside specialized vacuoles called autophagosomes, delivered to the lysosome for degradation forming autophagolysosomes. Verapamil and dantrolene prevented the increase of calpain-1 levels and preserved dystrophin, actin, and myosin loss/reduction as well cardiac contractile dysfunction associated with strikingly improved survival rate. These abnormal parameters emerge as therapeutic targets, which modulation may provide beneficial effects on future vascular outcomes and mortality in sepsis. Further studies are needed to shed light on this mechanism, mainly regarding specific calpain inhibitors. 相似文献
993.
994.
Maxime Culot Ana?lle Fabulas - da Costa Emmanuel Sevin Erica Szorath Stefan Martinsson Mila Renftel Yan Hongmei Romeo Cecchelli Stefan Lundquist 《PloS one》2013,8(12)
Historically, the focus has been to use in vitro BBB models to optimize rate of drug delivery to the CNS, whereas total in vivo brain/plasma ratios have been used for optimizing extent. However, these two parameters do not necessarily show good correlations with receptor occupancy data or other pharmacological readouts. In line with the free drug hypothesis, the use of unbound brain concentrations (Cu,br) has been shown to provide the best correlations with pharmacological data. However, typically the determination of this parameter requires microdialysis, a technique not ideally suited for screening in early drug development. Alternative, and less resource-demanding methodologies to determine Cu,br employ either equilibrium dialysis of brain homogenates or incubations of brain slices in buffer to determine fraction unbound brain (fu,br), which is subsequently multiplied by the total brain concentration to yield Cu,br. To determine Cu,br/Cu,pl ratios this way, still requires both in vitro and in vivo experiments that are quite time consuming. The main objective of this study was to explore the possibility to directly generate Cu,br/Cu,pl ratios in a single in vitro model of the BBB, using a co-culture of brain capillary endothelial and glial cells in an attempt to mimick the in vivo situation, thereby greatly simplifying existing experimental procedures. Comparison to microdialysis brain concentration profiles demonstrates the possibility to estimate brain exposure over time in the BBB model. A stronger correlation was found between in vitro Cu,br/Cu,pl ratios and in vivo Cu,br/Cu,pl obtained using fu,br from brain slice than with fu,br from brain homogenate for a set of 30 drugs. Overall, Cu,br/Cu,pl ratios were successfully predicted in vitro for 88% of the 92 studied compounds. This result supports the possibility to use this methodology for identifying compounds with a desirable in vivo response in the CNS early on in the drug discovery process. 相似文献
995.
Leigh Schulte Erica Lovas Kathryn Green Jason Mulvenna Geoffrey N. Gobert Garry Morgan Malcolm K. Jones 《International journal for parasitology》2013
The tegument, or body wall, of schistosomes is the primary tissue for host interaction and site targeted schistosome vaccination. However, many aspects of the cell biology, particularly differentiation and maintenance, remain uncharacterised. A leading vaccine candidate, Schistosoma mansoni tetraspanin 2 has proven efficacy in experimental models, but its function, precise subcellular location in the tegument and role in tegument biology is not well understood. A primary question is whether this molecule is a true surface molecule, that is, whether it appears within the apical membrane of the tegument. Hitherto, the target sequence for antibody localisation studies had not been available for advanced subcellular localisation studies, such as immuno-electron microscopy, due to aldehyde sensitivity. To circumvent this problem, we adapted the methods of high pressure freezing and cryosubstitution with uranyl acetate for immuno-electron microscopy. The tri-dimensional structure of tegument membranes was resolved using electron tomography. Immunolocalisation of Schistosoma mansoni tetraspanin 2 demonstrates that the molecule is localised to tegument membrane compartments, but predominantly within internal structures associated with surface invaginations and internal vesicles. Surprisingly, no label was found at the virtual surface of the parasite. The significance of this localisation pattern is discussed. 相似文献
996.
997.
Erica David 《Plant and Soil》2013,373(1-2):843-856
Aims
In cold-arid systems, moisture availability is often a limiting factor to vegetation establishment and growth. Consequentially, manipulating soil moisture dynamics may help to improve restoration practice. Application of snow fencing, for microclimate manipulation in cold-arid regions, improves native species establishment and restoration success following disturbance by improving soil moisture retention.Methods
Research was conducted in the Jonah Natural Gas Field, an area subjected to intensive gas development, in southwest Wyoming, USA, to assess roles of snow fencing in altering snowpack characteristics, and soil moisture, for improving re-establishment of native vegetation.Results
Application of a customized snow fence design (the Hollow Frame Fence System, HFFS) significantly increased vegetation establishment of the framework taxon, Artemisia tridentata Nutt. spp. wyomingensis Beetle & Young, and other native sagebrush-steppe species. The HFFS exhibited significantly fewer invasive species than control blocks; establishment of A. tridentata was significantly higher within the HFFS, as compared to both control blocks, and commercial fence types. Significant increases in spring soil moisture are likely drivers of increased restoration success with use of HFFS.Conclusions
The Hollow Frame Fence System provides increased water harvesting capacity necessary to improve habitat restoration in cold-arid environments subjected to disturbance. 相似文献998.
Erica Machlin Cox Selena M. Sagan Stefanie A.W. Mortimer Jennifer A. Doudna Peter Sarnow 《RNA (New York, N.Y.)》2013,19(12):1825-1832
The hepatitis C viral RNA genome forms a complex with liver-specific microRNA (miR-122) at the extreme 5′ end of the viral RNA. This complex is essential to stabilize the viral RNA in infected cultured cells and in the liver of humans. The abundances of primary and precursor forms of miR-122, but not the abundance of mature miR-122, are regulated in a circadian rhythm in the liver of animals, suggesting a possible independent function of precursor molecules of miR-122 in regulating viral gene expression. Modified precursor molecules of miR-122 were synthesized that were refractory to cleavage by Dicer. These molecules were found to enhance the abundance of HCV RNA. Furthermore, they diminished the expression of mRNAs that contained binding sites for miR-122 in their 3′ noncoding regions. By use of duplex and precursor miR-122 mimetic molecules that carried mutations in the passenger strand of miR-122, the effects on viral and reporter gene expression could be pinpointed to the action of precursor miR-122 molecules. Targeting the circadian expression of precursor miR-122 by specific compounds likely provides novel therapeutic strategies. 相似文献
999.
1000.
Erica J. Washington Mark J. Banfield Jeffery L. Dangl 《Microbiology and molecular biology reviews》2013,77(3):527-539