Thus far, our data suggest a role for COX in LPS-induced changes

Thus far, our data suggest a role for COX in LPS-induced changes in burrowing and open-field activity. To investigate the role of the different isoforms of COX we next compared the effect of

selective COX-1 and COX-2 inhibitors on LPS-induced behaviour changes. Fig. 5 shows the changes in burrowing tested 1–3 h after injection of LPS. Administration of LPS alone significantly decreased burrowing (Fig. 5, F(5,25) = 4.851, p = 0.0046) and mice pre-treated with the COX-1 selective inhibitors piroxicam and sulindac no longer differed from saline-treated mice. In contrast, pre-treatment with the selective COX-2 inhibitor nimesulide or niflumic acid had no effect and mice were still significantly impaired in the burrowing task. We next tested the effect of the inhibitors at CYC202 price various time points after injection of LPS to investigate the possibility that LPS-induced burrowing and open-field activity are differentially regulated over time as was previously reported for other behaviours (Swiergiel and Dunn, 2002). Fig. 6 shows the effect of LPS on burrowing and open-field activity at 2–4, 5–7 and 24 h after injection of LPS in mice pre-treated with the COX-1 specific inhibitor piroxicam or the COX-2 specific Selleckchem Ganetespib inhibitor nimesulide. The anti-inflammatory drugs were suspended in the same vehicle and given 30 min prior

to LPS. Administration of LPS significantly reduced burrowing at all time points tested. Piroxicam significantly reversed the effect of LPS on burrowing when tested between 2 and 4 h (Fig. 6, F(1,12) = 36.91, p < 0.0001). At later time points piroxicam was no longer protective, which may be explained by the short half life of drug in mice (T1/2 = 1.7 h) ( Milne and Twomey, 1980). Nimesulide (T1/2 = 2–3 h) ( Hull et al., 2005) did not significantly reverse the LPS-induced changes in burrowing at any time point tested ( Fig. 6). Similar results were observed for open-field activity: a clear trend towards protection of piroxicam at 2–4 h which disappeared at later time points. Pre-treatment

with the (-)-p-Bromotetramisole Oxalate drugs alone did not have an effect on burrowing or open-field activity. Interestingly, mice pre-treated with the COX-2 inhibitor appeared to recover better 24 h after LPS injection, compared to LPS-treated only or piroxicam pre-treated mice. The changes did not, however, reach significance. These results suggest that LPS-induced changes in burrowing and open-field activity between 2 and 4 h are largely mediated by COX-1 activity and show a minimal role for COX-2. Having established a key role of COX-1 in LPS-induced changes in burrowing and open-field activity, we next investigated the effect of piroxicam and nimesulide on cytokine and PG production. LPS increased serum IL-6 levels measured 3 h post challenge (Fig. 7A, F(3,16) = 5.893, p = 0.0091). Pre-treatment with piroxicam or nimesulide did not affect the serum levels of IL-6.

, 2007, Drew and Fraggos, 2007, Blackburn et al , 2005, Carthew e

, 2007, Drew and Fraggos, 2007, Blackburn et al., 2005, Carthew et al., 2009 and Escher et al., 2010). While there

is no generally accepted TTC of local effects in the respiratory tract, TTC values for systemic toxicity may be applied and after modification take into account for route to route differences between the respiratory tract and other organ systems (e.g., absorption, metabolism). However, so far adequate TTC models for inhalation route are under development (Carthew et al., 2009) and may become relevant in future. The described common principles can be applied to safety assessment of cosmetic sprays based on classical elements of risk assessment. The approach described relies on understanding external, systemic and in particular respiratory tract exposure see more and dose, understanding assessing potential toxicities and determination of safe exposure levels. The safety assessors will benefit from having access to improved exposure models and to standardized safety assessment methodologies utilized for spray product evaluation without interfering with the flexibility of the individual safety assessors who are Bioactive Compound Library cell assay responsible

for the safety of their products. This paper is intended to provide basic elements of a tiered safety assessment approach in order to increase transparency for regulators and reliability of results to the benefit of the consumer. It provides a recommendation to use these tools in the sense of a Weight-of-Evidence Approach when conducting the safety assessment. The Authors report no conflicts of interest. The Authors are employees of the companies Procter and Gamble,

KPSS-KAO Professional Salon Services GmbH, Beiersdorf AG, Henkel AG & Co. KGaA, L‘Oreal and the IKW (The German Cosmetic, Toiletry, Perfumery and Detergent Association). The Authors thank IKW for providing the discussion platform to develop this document. We thank K. Sarlo, and G. Nohynek as well as B. Hall, L. Merolla and 3-mercaptopyruvate sulfurtransferase W. Steiling as members of the Colipa Expert (ET) for Inhalation Toxicology & Exposure for the critical review of the manuscript. “
“Figure options Download full-size image Download as PowerPoint slide This Special Issue of Toxicology Letters is dedicated to Elsa Reiner in honor of her important contributions to the field of cholinesterases in their interactions with substrates, inhibitors and reactivators. Elsa Reiner had personal and scientific relationships with us and attended some of the International Medical Chemical Defence Conferences held at the Bundeswehr Medical Academy in Munich. Hence, we feel it highly appropriate to honor her memory at this occasion. Elsa Reiner was born in Osijek, Croatia, in 1930 where she spent her childhood before she moved with her parents to Zagreb. Here, she began to study chemistry and obtained her PhD degree in 1962.

The freedom allowed – the Foundation does not impose an agenda up

The freedom allowed – the Foundation does not impose an agenda upon the Vallee Visiting Professor – is perhaps the most desirable attribute

of the program. VVPs are free to use the time however it best suits their objectives (though it has become customary for them to give a public lecture while in residence), and when Jerrold Meinwald came from Cornell in October 1997, the freedom allowed him, among other this website things, to: write first drafts of three chapters for a book; complete or nearly complete four research manuscripts; write and submit a renewal for the NIH grant which supports all my insect related research; and attend several excellent Chemistry Department lectures in Cambridge. For Earl Davie, uninterrupted time was, in many ways, the single most important aspect of my stay at the Karolinska. Free from the usual distractions of telephone calls, administrative duties, and teaching obligations, Earl was able to spend nearly 3 hours every morning thinking and planning both new and old projects underway in our laboratory, which also made it possible to clarify new approaches for our future research. He remembers this time as a very beneficial and exciting experience in my scientific career. In some cases, the Vallee Visiting Professorship changed the direction of the participant’s career. This is perhaps best illustrated by the visit of Klaus Rajewsky. As Klaus approached mandatory retirement age

at the University of Cologne in Germany, it seemed that his career in research would have to come to an end. But, through mutual friends, Thiazovivin supplier Bert Vallee became aware of Klaus’

Farnesyltransferase situation and offered him a Vallee Visiting Professorship to explore research opportunities at Harvard Medical School (HMS). As Klaus reflects upon his visit, in the autumn of 1999, my wife and I spent six wonderful weeks in Boston, living in a Vallee-owned apartment…we loved the place, the many friends we made, the electric atmosphere of the medical campus and the general Boston/Cambridge environment. In 2001, we moved to Boston and I became a professor in the HMS Department of Pathology and PI at the Center for Blood Research. The generosity and hospitality of the Vallee Foundation were key to my transatlantic move and to many new bonds and friendships. When Gordon Hammes decided to resume laboratory work after a decade in academic administration, he was offered a Vallee Visiting Professorship. Gordon had been a very successful enzymologist, but after being away from the field for over a decade, wanted to reenter with a new approach. In his words, the professorship was pivotal in getting me started in an entirely new research field: single molecule studies of enzyme catalysis. At Harvard, I was able to talk to many excellent scientists. Most important, I had time to read and think without interruption. Within a year, I had constructed a single molecule apparatus, and my second research career was launched.

The recombinant protein was maintained at −80 °C and diluted in s

The recombinant protein was maintained at −80 °C and diluted in sterile phosphate buffered saline (PBS). Polyoma middle T oncogene-transformed mouse endothelioma cells derived from thymus (t-End) (Willians et al., 1988) were cultured in RPMI 1640 supplemented with Protein Tyrosine Kinase inhibitor 10% fetal bovine serum (FBS) in a 5% CO2, humidified atmosphere, at 37 °C. Cells were used in the 3rd passage. t-End cells were used to carry out the in vivo and in vitro studies in mice, and the expression of PECAM-1 was determined before the beginning of assays, which provided data about the responsiveness of the cell strain to be employed.

The dorsal skinfold chamber was implanted in male Swiss mice under anesthesia, as previously described by Harder et al. (2004). Amblyomin-X (1, 10 or 100 ng/10 μl) or PBS was topically applied and in sequence VEGF-A (10 ng/10 μl) or PBS (10 μl) was also locally applied. This treatment schedule was carried out on the 3rd, 5th and 7th days after chamber implantation. Animals were immobilized in a polycarbonate tube and the microcirculatory network in the windows was digitized using intravital microscopy equipment (Carl Zeiss, Germany) and photographed using a digital camera (Sony–Cyber-Shot – 7.2 Mega Pixels/Optical

3X, Japan). The images obtained before (day 3) and after the treatments (day 9) were quantified according to Dellian et al. (1996). Results were expressed as percentage of vessels in comparison to the control find more group of animals (PBS-treated animals). Fertilized chicken eggs were incubated (65% humidity, 37 °C), and on 11th day of incubation, a sterile cellulose disc (2 mm) was placed on the CAM and Ringer solution (10 μl, control), Amblyomin-X (100 ng/10 μl) with or without VEGF-A (0.25 ng/10 μl) was subsequently applied topically. Treatments were daily

until the 14th day. The discs were removed and photographed with a digital camera coupled to a magnifying glass (Nikon, magnification 1×). Quantification of CAM vascular network was assessed by counting the number of vessels present on the disc area. Results were expressed as percentage of vessels in comparison to control membranes, treated with Ringer PLEK2 solution. All experiments were conducted with a FACS Canto Flow Cytometer (Becton Dickinson, Mountain View, CA, USA) and analyzed using the Flow Jo (version 9.1) software. Data from 10.000 cells were obtained and only the morphologically viable endothelial cells were considered in the analysis. t-End confluent cells were incubated with PBS or Amblyomin-X (100 ng/ml) in medium supplemented with 10 or 1% BSA. Afterwards at 72 h, cells were harvested and necrosis and apoptosis were measured by adding propidium iodide (PI) or annexin-V, respectively. Cell proliferation was measured in adherent t-End cells labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) according to the manufacturer’s instructions.

4%) was the most frequently isolated species amongst the controls

4%) was the most frequently isolated species amongst the controls ( Table 2). No significant learn more differences in staphylococcus counts were observed amongst the subgroups for CD4T cells; however, counts were significantly lower in the subgroup with a viral load of less than 400 copies/mm3 (Table 3). The HIV-positive group showed a higher percentage of individuals positive

for Enterobacteriaceae and Pseudomonadaceae (77.7%) than the control (44.4%) (p = 0.001). Also, the counts of these microorganisms were significantly higher amongst HIV-positive patients than in the control group (p = 0.0001) ( Table 1). Enterobacter cloacae was the most frequently isolated species in both groups (18.8% in the HIV-positive group and 16.32% in the control group). Amongst Pseudomonadaceae species, Chryseomonas luteola was the most Selleckchem R428 common in both studied groups (7.3% in the HIV-positive group and 6.1% in the control group). Other species identified are shown in Table 4. Counts of Enterobacteriaceae and Pseudomonadaceae were significantly lower in the subgroup with <200 CD4 cells/mm3. With respect to viral load, significantly lower counts of staphylococci in the subgroup with <400 copies/mm3 were observed ( Table 3). One of the most challenging problems involving staphylococci has been their increasing resistance to methicillin, vancomycin and other antibiotics.23, 24 and 25 Oral reservoirs of these microorganisms may be

potential sources for infection in immunosuppressed

patients.26 In this study, staphylococci were isolated from 86.6% of the control group and 84.4% of HIV-positive patients. Previous studies reported a variable presence of staphylococcus in systemically diseased patients. These values varied from 28% amongst patients with malignant neoplasias3 to 96% in patients with rheumatoid arthritis.27 High percentages of patients positive for see more staphylococci in the oral cavity have been reported in the literature, with values from 94%27 to 95.6%28 amongst adults. Jackson et al.29 also observed a higher frequency of isolation in the oral cavities of healthy children (92%). The results obtained in this study confirm the conclusion of Smith et al.10 that staphylococcus species can often be isolated from the oral cavities of healthy or diseased children and adults. Although staphylococci have been considered part of the normal oral microbiota,27 and 29 their presence in the oral cavity may be associated with local and systemic infections, especially in immunosuppressed patients.10 With respect to the species identified in this study, S. epidermidis and S. aureus were the most prevalent coagulase-negative and coagulase-positive species, respectively, in both groups. The isolation of these species in the oral cavity and periodontal sites has been reported in the literature. 27, 28, 29, 30 and 31 The HIV-positive group showed a greater diversity of coagulase-negative species; the presence of S. warneri, S. capitis, S.

This was motivated by the goal of developing reliable satellite r

This was motivated by the goal of developing reliable satellite remote sensing methods for monitoring the phytoplankton biomass and primary productivity from space (see Siegel et al., 2013 and the references therein). Empirical relationships for estimating Chl from remote sensing reflectance Selleck Trichostatin A have been used for routine processing of global satellite imagery of ocean color since the beginning of the SeaWiFS mission in 1997 (O’Reilly et al., 1998 and O’Reilly et al., 2000). In the past several years, interpretation of ocean-color satellite data has progressed beyond the estimation of Chl to include new products. For example, it is now possible to determine

the dominant phytoplankton functional groups present in oceanic surface waters (e.g., Alvain et al., 2005 and Brewin et al., 2011) and to retrieve information about particle size distribution (Kostadinov et al., 2010 and Loisel et al., 2006). In addition, information about important components and processes of the oceanic carbon cycle

such as the primary productivity (Antoine et al., 1996, Behrenfeld and Falkowski, 1997 and Woźniak et al., 2007), the particulate organic carbon concentration (Duforet-Gaurier et al., 2010, Gardner et al., 2006, Stramska and Stramski, 2005 and Stramski et al., 2008), and the colored dissolved and detrital organic matter absorption (Maritorena et al., 2002 and Siegel et al., 2002)

can be derived from satellite data. Before these new data products are broadly used in oceanographic studies, it is extremely important AZD6244 to validate the performance of the various ocean color algorithms with observations. The main objective of this paper is to evaluate the performance of the standard NASA POC algorithm (Stramski et al., 2008). For POC product match-up analysis we have used coincident in situ data and satellite data from SeaWiFS and MODIS Aqua. We searched 16 years of satellite data from 1997 to 2012 for matchups with in situ data. In situ POC data have been obtained from public databases of the U.S. Joint Global Ocean Flux Study (U.S. JGOFS, and the SeaWiFS Bio-optical Carnitine dehydrogenase Archive and Storage System (SeaBASS), the publicly shared archive maintained by the NASA Ocean Biology Processing Group (OBPG) ( We have selected only these in situ data sets for which POC determinations were made using JGOFS protocols (Knap et al., 1996) and filters were acidified for removal of inorganic carbon prior to combustion. We have assumed that POC values of 10 mg m−3 and less were invalid in situ POC determinations if found outside the hyperoligotrophic waters of the South Pacific Subtropical Gyre (Stramski et al., 2008). We have found 2418 surface in situ POC concentration data fulfilling these requirements.

6% of the total zooplankton, with relatively high numbers of Sync

6% of the total zooplankton, with relatively high numbers of Synchaeta okai at stations EPZ015666 1, 3, 4 during summer. The diversity index value (H′) of the zooplankton community ranged between 0.66 and 2.16. The overall mean were 1.82 ± 0.26 (winter), 1.18 ± 0.37 (spring), 1.90 ± 0.15 (summer), 1.90 ± 0.15 (autumn). Diversity index values were generally higher during summer and autumn with parallel lower values of dominance at all stations. Station

1 attained higher values than those of the other stations. Highest density (annual average: 41.6 × 103 ind. m−3) was recorded at station 3, and lowest recorded at stations 6 and 7 (annual averages: 17.3 × 103 and 17.5 × 103 ind. m−3, respectively). Copepods were strongly dominant, making up the bulk of the zooplankton population. The highest copepod densities were observed in stations 6, 7, 5, 10 and 11. Copepod larval stages represented high percentage, fluctuated between 23.9% (station 6) and 65.9% (station 9) with an annual average of 42.1% of the total copepods. Protozoans were the most dominant group at stations 1, 2, 3 and 8, fluctuating between 37.2% (station 1) and 54.8% (station 3). Their abundance decreased to minimal at stations 6 and 7 (12.7% and 11.4%). Schmidingerella spp. were the most dominant fluctuating between 67.4% (station 1) and 96.2% (station 8). Rotifers were

third Pictilisib chemical structure in abundance (4.6%), and showed higher percentage at station 1 (12.0%) and decreased to reach minimal at stations 5 and 8. Cirripeds were relatively abundant in station 1 (10.3%), whereas in the other stations they accounted for only 0.3–2.7% of zooplankton numbers. Larvaceans contributed as little as 1.7% of the total count. The zooplankton standing crop was the smallest during winter (average: 11 ± 10.6 × 103 ind. m−3). The contribution of copepods to the total zooplankton has been represented by 69.5% with an increase of their larval stages (45.8%). Moreover, the dominant adult species was Oithona nana (19.0% of the total zooplankton). Protozoans were the second most abundant group making up 11.0% of the total zooplankton count. They were dominant by Schmidingerella

serrata and Tintinnopsis campanula Ehrenberg, Buspirone HCl 1840, representing respectively, 7.7% and 1.2% of the total zooplankton ( Fig. 3). During this season, cirripedes were represented by nauplii, which contributed 10.7% of the total count. Annelida constituted 6.3% of the total zooplankton with Spionid and Trochophore larvae were the dominant. In spring, the zooplankton crop was larger than other seasons (average: 31.3 ± 21.5 × 103 ind. m−3). It was the most productive season for protozoans, representing 78.2% of the total zooplankton. They were represented by 22 species (1 non tintinnid ciliates, 16 tintinnids and 5 foraminiferans) with the dominance of Schmidingerella serrata (73.9% of the total zooplankton). Copepods were the second dominant group, accounting for 17.6% of the total count.

The 4 perspectives were: (1) Recognizing and Defining the Problem

The 4 perspectives were: (1) Recognizing and Defining the Problem Eight domains of interest were initially agreed and discussed: hypoglycemia, therapy, care home diabetes, influence of comorbidities, glucose targets, family/carer perspectives, diabetes education, and patient safety. For those participants joining Navitoclax for the teleconference only, a brief summary of each domain was prepared by the moderator and each participant was given an opportunity to contribute further. We partly addressed the judgmental issue by asking participants to rank their level of agreement with each of the 4 perspectives according to the following scale (which was discussed and agreed

in advance): Figure options Download full-size image Download high-quality image (88 K) Download as PowerPoint slide The definitions of each grading scale are given in Appendix B. The moderator used a “voting” system when final comments and solutions were being offered

so as to reach consensus. After the conference weekend, the moderator produced a draft report and provided all participants with a chance to make further contributions. These were received, tabulated, and redistributed to members, and a second roundtable and international teleconference was held in Oxford, UK, in January 2011. A final consensus was then agreed. At the start of the roundtable, participants ranked the order of importance of the domains. For this part only, we show the influence of global experts in modifying the emphasis of the ranking grades. The overall ranking is shown in Table 1. Each domain was discussed in detail during the moderated discussions (available on request). The following statements CAL-101 manufacturer were agreed by consensus and a comment given in each case. These statements pertain to patients 70 years and older. Consensus statements (1) The clinician must consider Glycogen branching enzyme individual comorbidities, and cognitive and functional status when determining what glucose goals should be agreed with the patient and/or carer. Consensus statements (1) Because of the high risk of associated comorbidities in older people with diabetes, we recommend that regular CGA (Comprehensive

Geriatric Assessment) is used to identify related functional loss and the impact of disability. Consensus statements (1) Increasing age and progressive functional loss pose significant risks for patient safety. Delayed treatment and undertreatment are also important considerations. Hypoglycemia is defined for the purpose of this statement as a blood glucose level less than 4 mmol/L. Consensus statements (1) In older people, hypoglycemia is a highly prevalent and underrecognized disorder with severe consequences (eg, falls, cognitive impairment, hospital admission, and so forth). Consensus statements (1) All patients should participate as actively as possible in a tailored physical activity program involving resistance training, balance exercises, and cardiovascular fitness training.

However, investigators were racially diverse and from different d

However, investigators were racially diverse and from different disciplines (medicine, social sciences, ethics), and each read transcripts independently before reaching consensus. Our data emphasize that seriously ill patients fell into five ethically and clinically distinct variants across race/ethnicity. Respect for patient autonomy requires recognition of and respect for these variants and the appropriate implementation strategies they ensue. Patients’ autonomy can be enhanced by encouraging patients to make

and effectively communicate their decisions, subject to the limitations on doing so posed by “Avoiders” whose preferred decision-making style may not allow clinicians to promote and assist in advance care planning. The physician’s goal should be to click here promote effective EOL decision-making with Autonomists, Altruists, Authorizers, Absolute Trusters, and Avoiders. No one VE-822 size will fit all patients, whose implementation strategies may range from completing formal documents to increasing oral communication with surrogates. Physicians should judiciously allocate their time in a persistent, respectful, and supportive effort to engage patients in EOL care planning.

Patient-centered, culturally competent EOL decision-making is a powerful tool to ensure that patient preferences are truly upheld. Physicians have limited time to spend, requiring priorities to be set. Assisting Autonomists and Altruists to implement EOL decisions generally will be relatively simple: they

have made decisions and only need to effectively communicate them. Physicians can assist by providing appropriate Cell Penetrating Peptide paperwork or, for patients uncomfortable with written documents, strongly encouraging patients to discuss their wishes in detail with their legal surrogate decision maker(s). Surrogates will then be able to report the already-made decision of the patient, a role that is perceived as less burdensome [32] and [33]. Physicians could also facilitate discussions with potential surrogates and clarify to patients who their legal surrogates are [34]. Assisting some Authorizers may be relatively straightforward but can sometimes, along with assisting Absolute Trusters, be considered complex. This is because Authorizers first need to make clearer general value statements before they can effectively communicate them. Absolute Trusters by definition let others decide about their care. They can be strongly encouraged to give more guidance to their surrogates, moving them to Authorizers or, if they want to reduce the decision-making burden on surrogates, Altruists. Often this can be accomplished simply by pointing out how hard it is to make such important decisions for someone else without any guidance by that person [31], [32], [33] and [35].

It is, however, notable that NAPs

It is, however, notable that NAPs PARP inhibitor drugs by themselves do not exert as much influence as the BoNT/A complex, except for IL-6 which showed equal response (Table 1). MCP-1 and VEGF were two other cytokines which were induced by NAPs alone, albeit not as strongly as BoNT/A complex. BoNT/A complex and NAPs both contain associated proteins for BoNT/A. However, exposition to BoNT/A complex, but not to NAPs,

resulted in significant increase of IP-10, IL-8, IL-15, TNF-α, and RANTES. For the current research, cytokine release was examined after 48 h of incubation. The kinetics of cytokine release have been studied for 24 h to up to one week in lymphocyte (Arva and Andersson, 1999) and kinetics of TNF, IL-6, and IL-8 gene expression after inflammatory stimuli BAY 80-6946 supplier have been shown to have multiple peak at 2–4 h and 24 h (DeForge and Remick, 1991). Although no cytokine release was induced by pure BoNT/A in the current experimental setting, further investigation with different incubation time on complex patterns of cytokine gene expression and production with pure BoNT/A as well as other components of BoNT/A complex is needed. Higher effect of BoNT/A

complex could arise from one or more of the following reasons. One, there is higher level of binding of the BoNT/A in the BoNT/A complex allowing more NAPs to enter the cell. Two, interaction between BoNT/A and NAPs introduce conformational changes which are more critical for triggering cytokine response. Three, there is a physiological link between the effects of BoNT/A and NAPs intracellularly, leading to synergistic host cell response. A previous study on the co-culture of microglia and SH-SY5Y

cells has shown the expression of IL-6, IL-8, and MCP-1 with borrelia burgdorferi stimulation, a spirochete that causes lyme disease, and it is known to potently induce the production of inflammatory mediators in a variety of cells (Myers et al., 2009). Release of MCP-1 from SH-SY5Y has also been reported during the neuroinflammation process (Mitchell et al., 2009). Physiological Chlormezanone role of cytokine release in neuronal cells can be manifold. The presence and activity of pro-inflammatory cytokines IL-1β and TNF-α were first reported in human and rat brain a decade ago (Breder et al., 1988 and Plata-Salaman et al., 1988). Cytokine release studies enable us to identify cytokines that are produced specifically upon BoNT/A, its complex, or NAPs stimulation. The SH-SY5Y cell line has been proven to be a useful in vitro model for TNF production from neurons and the regulation of that production by alpha2-adrenergic receptor activation (Renauld and Spengler, 2002). Additionally, TNF-α has been shown not only play the critical roles in pathological development and inflammatory induction, but on modulating cell proliferation of neural progenitors in CNS inflammation (Downen et al., 1999 and Wu et al., 2000).