182 research outputs found
In Vitro Cytotoxic Effect of Aqueous Extracts from Leaves and Rhizomes of the Seagrass Posidonia oceanica (L.) Delile on HepG2 Liver Cancer Cells: Focus on Autophagy and Apoptosis
Aqueous extracts from Posidonia oceanicaâs green and brown (beached) leaves and rhizomes
were prepared, submitted to phenolic compound and proteomic analysis, and examined for their
potential cytotoxic effect on HepG2 liver cancer cells in culture. The chosen endpoints related to
survival and death were cell viability and locomotory behavior, cell-cycle analysis, apoptosis and
autophagy, mitochondrial membrane polarization, and cell redox state. Here, we show that 24 h
exposure to both green-leaf- and rhizome-derived extracts decreased tumor cell number in a doseâ
response manner, with a mean half maximal inhibitory concentration (IC50) estimated at 83 and
11.5 ”g of dry extract/mL, respectively. Exposure to the IC50 of the extracts appeared to inhibit cell
motility and long-term cell replicating capacity, with a more pronounced effect exerted by the rhizomederived preparation. The underlying death-promoting mechanisms identified involved the downregulation of autophagy, the onset of apoptosis, the decrease in the generation of reactive oxygen
species, and the dissipation of mitochondrial transmembrane potential, although, at the molecular
level, the two extracts appeared to elicit partially differentiating effects, conceivably due to their
diverse composition. In conclusion, P. oceanica extracts merit further investigation to develop novel
promising prevention and/or treatment agents, as well as beneficial supplements for the formulation
of functional foods and food-packaging material with antioxidant and anticancer propertie
Arterially Perfused Neurosphere-Derived Cells Distribute Outside the Ischemic Core in a Model of Transient Focal Ischemia and Reperfusion In Vitro
BACKGROUND: Treatment with neural stem cells represents a potential strategy to improve functional recovery of post-ischemic cerebral injury. The potential benefit of such treatment in acute phases of human ischemic stroke depends on the therapeutic viability of a systemic vascular delivery route. In spite of the large number of reports on the beneficial effects of intracerebral stem cells injection in experimental stroke, very few studies demonstrated the effectiveness of the systemic intravenous delivery approach. METODOLOGY/PRINCIPAL FINDINGS: We utilized a novel in vitro model of transient focal ischemia to analyze the brain distribution of neurosphere-derived cells (NCs) in the early 3 hours that follow transient occlusion of the medial cerebral artery (MCA). NCs obtained from newborn C57/BL6 mice are immature cells with self-renewal properties that could differentiate into neurons, astrocytes and oligodendrocytes. MCA occlusion for 30 minutes in the in vitro isolated guinea pig brain preparation was followed by arterial perfusion with 1x10(6) NCs charged with a green fluorescent dye, either immediately or 60 minutes after reperfusion onset. Changes in extracellular pH and K(+) concentration during and after MCAO were measured through ion-sensitive electrodes. CONCLUSION/SIGNIFICANCE: It is demonstrated that NCs injected through the vascular system do not accumulate in the ischemic core and preferentially distribute in non-ischemic areas, identified by combined electrophysiological and morphological techniques. Direct measurements of extracellular brain ions during and after MCA occlusion suggest that anoxia-induced tissue changes, such as extracellular acidosis, may prevent NCs from entering the ischemic area in our in vitro model of transitory focal ischemia and reperfusion suggesting a role played by the surrounding microenviroment in driving NCs outside the ischemic core. These findings strongly suggest that the potential beneficial effect of NCs in experimental focal brain ischemia is not strictly dependent on their homing into the ischemic region, but rather through a bystander mechanism possibly mediated by the release of neuroprotective factors in the peri-infarct region
Performance of ALICE pixel prototypes in high energy beams
The two innermost layers of the ALICE inner tracking system are instrumented
with silicon pixel detectors. Single chip assembly prototypes of the ALICE
pixels have been tested in high energy particle beams at the CERN SPS.
Detection efficiency and spatial precision have been studied as a function of
the threshold and the track incidence angle. The experimental method, data
analysis and main results are presented.Comment: 10 pages, 9 figures, contribution to PIX2005 Workshop, Bonn
(Germany), 5-8 September 200
Beam Test Performance and Simulation of Prototypes for the ALICE Silicon Pixel Detector
The silicon pixel detector (SPD) of the ALICE experiment in preparation at
the Large Hadron Collider (LHC) at CERN is designed to provide the precise
vertex reconstruction needed for measuring heavy flavor production in heavy ion
collisions at very high energies and high multiplicity. The SPD forms the
innermost part of the Inner Tracking System (ITS) which also includes silicon
drift and silicon strip detectors. Single assembly prototypes of the ALICE SPD
have been tested at the CERN SPS using high energy proton/pion beams in 2002
and 2003. We report on the experimental determination of the spatial precision.
We also report on the first combined beam test with prototypes of the other ITS
silicon detector technologies at the CERN SPS in November 2004. The issue of
SPD simulation is briefly discussed.Comment: 4 pages, 5 figures, prepared for proceedings of 7th International
Position Sensitive Detectors Conference, Liverpool, Sept. 200
The ALICE Silicon Pixel Detector System (SPD)
The ALICE silicon pixel detector (SPD) comprises the two innermost layers of the ALICE inner tracker system. The SPD includes 120 detector modules (half-staves) each consisting of 10 ALICE pixel chips bump bonded to two silicon sensors and one multi-chip read-out module. Each pixel chip contains 8192 active cells, so that the total number of pixel cells in the SPD is â 107. The on-detector read-out is based on a multi-chip-module containing 4 ASICs and an optical transceiver module. The constraints on material budget and detector module dimensions are very demanding
Performance of prototypes for the ALICE electromagnetic calorimeter
The performance of prototypes for the ALICE electromagnetic sampling
calorimeter has been studied in test beam measurements at FNAL and CERN. A
array of final design modules showed an energy resolution of about
11% / 1.7 % with a uniformity of the response
to electrons of 1% and a good linearity in the energy range from 10 to 100 GeV.
The electromagnetic shower position resolution was found to be described by 1.5
mm 5.3 mm /. For an electron identification
efficiency of 90% a hadron rejection factor of was obtained.Comment: 10 pages, 10 figure
The Drosophila Gap Gene Network Is Composed of Two Parallel Toggle Switches
Drosophila âgapâ genes provide the first response to maternal gradients in the early fly embryo. Gap genes are expressed in a series of broad bands across the embryo during first hours of development. The gene network controlling the gap gene expression patterns includes inputs from maternal gradients and mutual repression between the gap genes themselves. In this study we propose a modular design for the gap gene network, involving two relatively independent network domains. The core of each network domain includes a toggle switch corresponding to a pair of mutually repressive gap genes, operated in space by maternal inputs. The toggle switches present in the gap network are evocative of the phage lambda switch, but they are operated positionally (in space) by the maternal gradients, so the synthesis rates for the competing components change along the embryo anterior-posterior axis. Dynamic model, constructed based on the proposed principle, with elements of fractional site occupancy, required 5â7 parameters to fit quantitative spatial expression data for gap gradients. The identified model solutions (parameter combinations) reproduced major dynamic features of the gap gradient system and explained gap expression in a variety of segmentation mutants
The ALICE Silicon Pixel Detector: readiness for the first proton beam
The Silicon Pixel Detector (SPD) is the innermost element of the ALICE Inner Tracking
System (ITS). The SPD consists of two barrel layers of hybrid silicon pixels surrounding the
beam pipe with a total of 48 10^7 pixel cells. The SPD features a very low material budget, a 99.9%
efficient bidimensional digital response, a 12 micron spatial precision in the bending plane (rf ) and a
prompt signal as input to the L0 trigger. The SPD commissioning in the ALICE experimental area
is well advanced and it includes calibration runs with internal pulse and cosmic ray runs. In this
contribution the commissioning of the SPD is reviewed and the first results from runs with cosmic
rays and circulating proton beams are presented
Safety profile of enhanced thromboprophylaxis strategies for critically ill COVID-19 patients during the first wave of the pandemic: observational report from 28 European intensive care units
Introduction: Critical illness from SARS-CoV-2 infection (COVID-19) is associated with a high burden of pulmonary embolism (PE) and thromboembolic events despite standard thromboprophylaxis. Available guidance is discordant, ranging from standard care to the use of therapeutic anticoagulation for enhanced thromboprophylaxis (ET). Local ET protocols have been empirically determined and are generally intermediate between standard prophylaxis and full anticoagulation. Concerns have been raised in regard to the potential risk of haemorrhage associated with therapeutic anticoagulation. This report describes the prevalence and safety of ET strategies in European Intensive Care Unit (ICUs) and their association with outcomes during the first wave of the COVID pandemic, with particular focus on haemorrhagic complications and ICU mortality. Methods: Retrospective, observational, multi-centre study including adult critically ill COVID-19 patients. Anonymised data included demographics, clinical characteristics, thromboprophylaxis and/or anticoagulation treatment. Critical haemorrhage was defined as intracranial haemorrhage or bleeding requiring red blood cells transfusion. Survival was collected at ICU discharge. A multivariable mixed effects generalised linear model analysis matched for the propensity for receiving ET was constructed for both ICU mortality and critical haemorrhage. Results: A total of 852 (79% male, age 66 [37\u201385] years) patients were included from 28 ICUs. Median body mass index and ICU length of stay were 27.7 (25.1\u201330.7) Kg/m2 and 13 (7\u201322) days, respectively. Thromboembolic events were reported in 146 patients (17.1%), of those 78 (9.2%) were PE. ICU mortality occurred in 335/852 (39.3%) patients. ET was used in 274 (32.1%) patients, and it was independently associated with significant reduction in ICU mortality (log odds = 0.64 [95% CIs 0.18\u20131.1; p = 0.0069]) but not an increased risk of critical haemorrhage (log odds = 0.187 [95%CI 12 0.591 to 12 0.964; p = 0.64]). Conclusions: In a cohort of critically ill patients with a high prevalence of thromboembolic events, ET was associated with reduced ICU mortality without an increased burden of haemorrhagic complications. This study suggests ET strategies are safe and associated with favourable outcomes. Whilst full anticoagulation has been questioned for prophylaxis in these patients, our results suggest that there may nevertheless be a role for enhanced / intermediate levels of prophylaxis. Clinical trials investigating causal relationship between intermediate thromboprophylaxis and clinical outcomes are urgently needed
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