Investigation of aspects of reactive gliosis in human astrocytoma cell lines:application for toxicity assessment

The process of astrogliosis, or reactive gliosis, is a typical response of astrocytes to a wide range of physical and chemical injuries. The up-regulation of the astrocyte specific glial fibrillary acidic protein (GFAP) is a hallmark of reactive gliosis and is widely used as a marker to identify the response. In order to develop a reliable, sensitive and high throughput astrocyte toxicity assay that is more relevant to the human response than existing animal cell based models, the U251-MG, U373-MG and CCF-STTG 1 human astrocytoma cell lines were investigated for their ability to exhibit reactive-like changes following exposure to ethanol, chloroquine diphosphate, trimethyltin chloride and acrylamide. Cytotoxicity analysis showed that the astrocytic cells were generally more resistant to the cytotoxic effects of the agents than the SH-SY5Y neuroblastoma cells. Retinoic acid induced differentiation of the SH-SY5Y line was also seen to confer some degree of resistance to toxicant exposure, particularly in the case of ethanol. Using a cell based ELISA for GFAP together with concurrent assays for metabolic activity and cell number, each of the three cell lines responded to toxicant exposure by an increase in GFAP immunoreactivity (GFAP-IR), or by increased metabolic activity. Ethanol, chloroquine diphosphate, trimethyltin chloride and bacterial lipopolysaccharide all induced either GFAP or MTT increases depending upon the cell line, dose and exposure time. Preliminary investigations of additional aspects of astrocytic injury indicated that IL-6, but not TNF-α. or nitric oxide, is released following exposure to each of the compounds, with the exception of acrylamide. It is clear that these human astrocytoma cell lines are capable of responding to toxicant exposure in a manner typical of reactive gliosis and are therefore a valuable cellular model in the assessment of in vitro neurotoxicity.

Further preliminary assessment of three human glioma cell lines as models of human astrocytic toxicity in vitro

Three human astroglioma lines U251-MG, U373-MG and CCF-STTG1 have been evaluated further as possible models for astrocytotoxicity (GFAP and IL-6 release). The effects of bacterial lipopolysaccharide, chloroquine diphosphate and acrylamide were studied on GFAP expression and LPS, chloroquine diphosphate, ethanol, trimethyltin chloride (TMTC) and acrylamide were examined on interleukin-6 (IL-6) release in the U373-MG line only. At 4-h LIPS elevated GFAP (17.0±5.0% P < 0.05) above control in the U251-MG cell line only. Chloroquine diphosphate over 4 h in the U251-MG line resulted in an increase in GFAP-IR to 20.3 ±4.2% and 21.1 ± 4.1 % above control levels 0.1 µM (P< 0.05) and 1 µM (P< 0.05) respectively. CQD was associated with decreases in MTT turnover, particularly after 24 h incubation. With the U373-MG line, LPS (0.5 µg/ml) increased IL-6 expression 640% above control (P < 0.001), whilst chloroquine diphosphate (100 µM), ethanol (10mM) and TMTC chloride (1 µM) also increased IL-6. It is possible that batteries of astrocytic human glioma cell lines may be applicable to the sensitive evaluation of toxicants on astrogliotic expression markers such as GFAP and IL-6.

Assessment of the astrogliotic responses of three human astrocytoma cell lines to ethanol, trimethyltin chloride and acrylamide

The astrogliotic responses of the CCF-STTG1, U251-MG, and U373-MG human astrocytoma lines were determined after exposure to ethanol, trimethyltin chloride (TMTC), and acrylamide over 4, 16, and 24 h. Basal glial fibrillary acidic protein (GFAP) expression in the U-251MG and U373-MG cells was 10-fold greater than the CCF-STGG1 line. Ethanol treatment over 24 h, but not at 4 and 16 h, resulted in significant increases in GFAP in all three glioma lines at sub-cytotoxic levels; the GFAP responses in the CCF-STTG1 line were the most sensitive, as concentrations of 0.1 and 1 mM led to increases in GFAP expression compared with control of 56.8 ± 15.7 and 58.9 ± 11.5%, respectively (P < 0.05). Treatment with TMTC (1 μM) over 4 h showed elevated GFAP expression in the U251-MG cell line to 28.0 ± 15.7% above control levels (P < 0.01), but not in the other U373-MG or CCF-STTG1 cells. At 4 h, MTT turnover was markedly increased compared with control, particularly in the U373-MG line at concentrations as low as 1 μM (17.1 ± 2.3%; P < 0.01). TMTC exposure over 16 and 24 h resulted in reduction in GFAP expression in all three lines at concentrations; at 24 h incubation, the reduction was >50% (P < 0.01). There were no changes in GFAP expression or MTT turnover in response to acrylamide except at the highest concentration ranges of 10-100 mM. This study underlines the significance of period of exposure, as well as toxin concentration in astrocytoma cellular response to toxic pressure. © 2007 Elsevier Ireland Ltd. All rights reserved.

The toxicity of hexanedione isomers in neural and astrocytic cell lines

The metabolite 2,5-hexanedione (HD) is the cause of neurotoxicity linked with chronic n-hexane exposure. Acute exposure to high levels of 2,5-HD, have also shown toxic effects in neuronal cells and non-neuronal cells. Isomers of 2,5-HD, 2,3- and 3,4-HD, added to foodstuffs, are reported to be non-toxic. The acute cytotoxic effects of 2,5-, 2,3- and 3,4-HD were evaluated in neural (NT2.N, SK-N-SH), astrocytic (CCF-STTG1) and non-neural (NT2.D1) cell lines. All the cell lines were highly resistant to 2,5-HD (34-426 mM) at 4-h exposure, although sensitivity was greatest with NT2.D1, then SK-N-SH, NT2.N and finally the CCF-STTG1 line. At 24-h exposure, cell vulnerability increased 5-10-fold. The NT2.D1 cells were again the most sensitive, followed by NT2.N, SK-N-SH and then the CCF-STTG1 cells. 2,3- and 3,4-HD (8-84 mM), were significantly more toxic towards all four cell lines compared with 2,5-HD, after 4-h exposure. After 24-h exposure there was a 12-fold increase in inhibition of MTT turnover in the SK-N-SH cells and a 4-fold increase in the CCF-STTG1 cells, compared with 2,5-HD exposure. 2,3- and 3,4-HD, were significantly less toxic to the NT2.N cells than the SK-N-SH cells after 24-h exposure to the compounds, demonstrating a differing toxin vulnerability between these neural and neuroblastoma cell lines. This study indicates that these non-neuronal and neuronal cells are acutely resistant to 2,5-HD cytotoxicity, whilst the previously unreported sensitivity of all four cell lines to the 2,3- and 3,4- isomers of HD to has been shown to be significantly greater than that of 2,5-HD. © 2006 Elsevier B.V. All rights reserved.

Natura 2000 erdők közgazdasági környezetének elemzése (Assessment of the economic environment of Natura 2000 forests)

Ebben a tanulmányban a Natura 2000 erdők közgazdasági kérdéseit jártuk körül az ökoszisztéma-szolgáltatások koncepciójának segítségével, nemzetközi és hazai szakirodalomra építve. Emellett a természetközeli erdőgazdálkodás fogalomkörét, s azon belül a folyamatos erdőborítást szolgáló erdőgazdálkodást vettük alapul. A következőkben néhány összegző megállapítást teszünk, és kijelölünk további kutatási irányokat. _____ This study has been prepared within the LIFEinFORESTS – Improved communication, cooperation and capacity building for preserving biodiversity in Natura 2000 forests (B2 action, LIFE13 INF/HU/001163) – project in the framework of LIFE+ Information and Communication under the contract signed with the Duna-Ipoly National Park Directorate. The main aim of the study is to summarize the international and Hungarian economic and environmental economic literature related to the Natura 2000 forests, and serve as a background study for the communication with and training of forest owners and users operating at Natura 2000 sites. The concept of ecosystem services (ESs) is used as an overall framework for the study. In our opinion it is able to show all the benefits provided by forests and can also help to reveal that the benefits of nature-oriented, continuous cover forest management (CCF) can exceed the benefits of traditional rotation forest management (RFM). The definition and the classification of the Millennium Ecosystem Assessment (MA, 2003, 2005) is used throughout the study, so provisioning, cultural, regulating and supporting services are distinguished.

Uso de correntropia na generalização de funções cicloestacionárias e aplicações para a extração de características de sinais modulados

Information extraction is a frequent and relevant problem in digital signal processing. In the past few years, different methods have been utilized for the parameterization of signals and the achievement of efficient descriptors. When the signals possess statistical cyclostationary properties, the Cyclic Autocorrelation Function (CAF) and the Spectral Cyclic Density (SCD) can be used to extract second-order cyclostationary information. However, second-order cyclostationary information is poor in nongaussian signals, as the cyclostationary analysis in this case should comprise higher-order statistical information. This paper proposes a new mathematical tool for the higher-order cyclostationary analysis based on the correntropy function. Specifically, the cyclostationary analysis is revisited focusing on the information theory, while the Cyclic Correntropy Function (CCF) and Cyclic Correntropy Spectral Density (CCSD) are also defined. Besides, it is analytically proven that the CCF contains information regarding second- and higher-order cyclostationary moments, being a generalization of the CAF. The performance of the aforementioned new functions in the extraction of higher-order cyclostationary characteristics is analyzed in a wireless communication system where nongaussian noise exists.

Breast pumps as an incentive for breastfeeding : a mixed methods study of acceptability

Funding acknowledgement This project was funded by the NIHR Health Technology Assessment Programme (10/31/02) and is published in full in Health Technology Assessment.. Further information available at: http://www.nets.nihr.ac.uk/projects/hta/103102 This paper presents independent research commissioned by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the HTA programme or the Department of Health. NIHR were not involved in the study design, collection, analysis and interpretation of data or in the writing of the articles for publication.

Breast pumps as an incentive for breastfeeding : a mixed methods study of acceptability

Funding acknowledgement This project was funded by the NIHR Health Technology Assessment Programme (10/31/02) and is published in full in Health Technology Assessment.. Further information available at: http://www.nets.nihr.ac.uk/projects/hta/103102 This paper presents independent research commissioned by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the HTA programme or the Department of Health. NIHR were not involved in the study design, collection, analysis and interpretation of data or in the writing of the articles for publication.

Costs, quality of life and cost-effectiveness of open and arthroscopic repair for rotator cuff tears : economic evaluation alongside the UKUFF trial

FUNDING & ACKNOWLEDGEMENTS This project was funded by the NIHR Health Technology Assessment programme (project number 05/47/02) and is published in full in Health Technology Assessment; Vol. 19, No. 80. Further information available at: http://www.nets.nihr.ac.uk/projects/hta/054702 This paper presents independent research commissioned by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the HTA programme or the Department of Health. Due to the confidential nature of the trial data supporting this publication not all of the data can be made accessible to other researchers. Please contact the UKUFF study principal investigator Andrew Carr (andrew.carr@ndorms.ox.ac.uk) for more information. The authors wish to thank the UKUFF trial collaborators for their contribution in managing the conduct of the trial, and for their comments on the interim economic results: Marion Campbell and Hannah Bruhn (Centre for Healthcare Randomised Trials, HSRU, University of Aberdeen), Jonathan Rees MD and David Beard (NDORMS, University of Oxford; NIHR Oxford Biomedical Research Centre), Jane Moser (NDORMS, University of Oxford), Raymond Fitzpatrick and Jill Dawson (NDPH, University of Oxford).

Constructing strongly-MDS convolutional codes with maximum distance profile

This paper revisits strongly-MDS convolutional codes with maximum distance profile (MDP). These are (non-binary) convolutional codes that have an optimum sequence of column distances and attains the generalized Singleton bound at the earliest possible time frame. These properties make these convolutional codes applicable over the erasure channel, since they are able to correct a large number of erasures per time interval. The existence of these codes have been shown only for some specific cases. This paper shows by construction the existence of convolutional codes that are both strongly-MDS and MDP for all choices of parameters.

There exists circularity between WACC and value? Another solution.

Although we know there exists a simple approach to solve the circularity between value and the discount rate, known as the Adjusted Present Value proposed by Myers, 1974, it seems that practitioners still rely on the traditional Weighted Average Cost of Capital, WACC approach of weighting the cost of debt, Kd and the cost of equity, Ke and discounting the Free Cash Flow, FCF. We show how to solve circularity when calculating value with the free cash flow, FCF and the WACC. As a result of the solution we arrive at a known solution when we assume the discount rate of the tax equity: the capital cash flow, CCF discounted at Ku. When assuming Kd as the discount rate for the tax savings, we find an expression for calculating value that does not implies circularity. We do this for a single period and for N periods.

Regimes alimentares no cavalo de desporto : a utilização de alimentos compostos complementares na suplementação das dietas

Dissertação de Mestrado em Engenharia Zootécnica / Produção Animal