Per-protocol analyses for primary outcomes corroborated the stati

Per-protocol analyses for primary outcomes corroborated the statistical significance and clinical relevance of the intention-to-treat results (Table 3), including time

to initial clinical response (Fig. 3). The remaining per-protocol results were generally comparable to the observed intention-to-treat results and, therefore, are not reported herein. The clinical response and relapse profiles of these patients with moderate to severe chronic LBP provide a unique perspective on the short-term outcomes of OMT. Patients who received OMT experienced about twice as much learn more substantial LBP improvement over time as those who received sham OMT. A large majority of rapid responders who were identifiable after one scheduled OMT

session maintained a clinical response to OMT at the week 12 exit visit. Typically, in patients who were clinical responders to OMT at week 12, three scheduled treatment sessions within four weeks were sufficient to cross the 50% pain reduction threshold for substantial LBP improvement. Thus, it appears that relatively few treatment sessions may be needed to attain and predict short-term response to OMT. The large effect size for overall short-term efficacy of OMT was driven by stable responders who never dropped below the 50% pain reduction threshold for substantial LBP improvement throughout the study. With the caveats of limited sample size and statistical power, and originally unplanned analyses, our subgroup analyses yielded findings Interleukin-2 receptor that may help guide future studies in this field. There were very large RRs for Trametinib cost stable clinical response and clinical response at the week 12 exit visit in the subgroup

of patients with co-morbid depression vs. those without depression, although patients with depression were more likely to relapse. Other subgroups that consistently exhibited large RRs for stable clinical response and clinical response at the week 12 exit visit, coupled with small RRs for relapse, included those in the 21–39 year age category; current cigarette smokers; and patients with LBP duration greater than one year, greater deficits in back-specific functioning, and poorer general health. Although OMT was associated with decreased need of prescription rescue mediation (RR, 0.66; 95% CI, 0.43–1.00) in the originally reported outcomes of the OSTEOPATHIC Trial (Licciardone et al., 2013b), our present findings suggest that patients who concurrently use non-prescription medication for LBP may experience an enhanced response to OMT and decreased likelihood of relapse. It is interesting to review potential mechanisms by which OMT may exert its treatment effects in light of our subgroup findings. Previous analyses of OSTEOPATHIC Trial data have found reductions in serum tumor necrosis factor (TNF)-α concentration (Licciardone et al., 2012) and remission of psoas syndrome (Licciardone et al.

Human umbilical vein endothelial cells (HUVEC) (Lot#0000120825; L

Human umbilical vein endothelial cells (HUVEC) (Lot#0000120825; Lonza®, Walkersville, MD, USA) were cultured at 37 °C and 5% CO2 in endothelial basal media (EBM-2) supplemented with a bullet kit (Lonza®) containing human fibroblast growth factor B, hydrocortisone, vascular endothelial growth factor, ascorbic acid, heparin, human

Rapamycin in vivo endothelial growth factor, and fetal bovine serum. For cell passage, cultures were incubated to approximately 40% confluence within the culture flask, according to LONZA guidelines. For experiments, cultures were incubated to approximately 50% confluence then harvested by exposure to trypsin–EDTA (Lonza®) for 2 min at 37 °C. Cell suspensions were centrifuged at 201g for 5 min in a 5810R tabletop centrifuge (Eppendorf,

Westbury, NY, USA), and resuspended in endothelial growth media at a concentration of 1.0 × 106 cells/mL in 1 mL aliquots maintained in 12 × 75 mm round bottom plastic tubes (VWR, Edmonton Canada) prior to experimentation. The dual fluorescent assay (SytoEB) Bcl-2 inhibitor uses a combination of two fluorescent dyes, Syto13 (Molecular Probes, Eugene, OR, USA) and ethidium bromide (EB) (Sigma–Aldrich, Mississauga, ON, Canada) to assess cell membrane integrity. Syto13 is a DNA/RNA binding stain that permeates all cells and fluoresces green on excitation by UV wavelengths. Ethidium bromide permeates cells with damaged plasma membranes, exhibiting red fluorescence upon UV exposure. The combination of these two dyes makes a binary assay with membrane intact cells exhibiting green fluorescence (Syto13) and membrane compromised cells exhibiting red fluorescence (EB). The SytoEB stain was prepared using 1× phosphate buffered saline (PBS), and aliquots of Syto and EB diluted from the stock solution. The final dye was comprised of 25 μM EB and 12.5 μM Syto13. 10 μL of the prepared dye were added to the 1 mL aliquot of HUVEC in suspension and incubated for 2 min at room temperature before analysis. The ratiometric dye 5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine-iodide

(JC-1) (Molecular Probes, Eugene, OR, USA) was used as an indicator of mitochondrial membrane potential before of HUVEC in suspension. The fluorescence shifts from green (∼525 nm) in low polarization states (non-functional mitochondria) to red (∼590 nm) in high polarization states (functioning mitochondria). This change in color of fluorescence is based on a concentration-dependent shift from monomers of the dye which fluoresce green to J-aggregates which fluoresce red [34]. Initially the dye is present as cationic monomers (green) that permeate into cells, influenced by the negative intracellular potential. In healthy cells these monomers permeate into the mitochondrial matrix, drawn by the electronegative interior of mitochondria where these monomers form J-aggregates (red) [15].

Our dynamics study of cancellous bone adjacent to cortical bone (

Our dynamics study of cancellous bone adjacent to cortical bone (Fig. 3D) showed that mineralization occurred between the first and second labelings, but not between the second labeling and osteoid formation during the 28-day period before biopsy, which implied that the mineralization had occurred due to promotion of food intake in hospital, while the later lack of mineralization was caused by poor eating outside hospital. Malnutrition with vitamin D depletion may

have a negative influence on bone formation due to impairment of mineralization. The presence of GSI-IX ic50 ‘Empty lacunae’ (Fig. 3E) is supported by Mullender et al. [9]. Bone is a dynamic tissue that undergoes continuous renewal.

Its mechanical integrity is ensured by removal of old bone and subsequent replacement by new bone. A negative balance between the processes of resorption and formation may cause progressive bone loss in patients with osteoporosis. Osteocytes play a role in the regulation of bone remodeling. Because our patient’s bone mass and kidney injury improved after weight gain and normalization of serum potassium by a highly nutritious diet, malnutrition with vitamin D depletion and hypokalemia may have a negative influence on bone formation due to impairment of mineralization, and bone resorption by osteoclasts may be activated via the formation of empty lacunae, though this was not confirmed by repeat bone biopsy to assess the changes after weight gain. In summary, our patient was found to have severe osteoporosis by DEXA and bone biopsy, as well as chronic interstitial nephritis selleck inhibitor on renal biopsy. Her BMD, renal dysfunction and hypokalemia improved after weight gain of 10 kg (BMI increased from 11.0 to 15.0), which indicates that malnutrition including hypokalemia

contributes to the pathogenesis of premenopausal osteoporosis and renal dysfunction over in this patient. Thus, unlike postmenopausal osteoporosis, it may not require pharmacological therapy such as bisphosphonates or teriparatide. This is the first report on the bone histological features of premenopausal osteoporosis in a patient with AN and kidney injury. We thank Akemi Ito of the Ito bone histomorphometry institute for performing histomorphometric analysis. “
“The prediction interval (PI) reported on page 107, paragraph 3, line 6 contained an error. The corrected sentence appears below. The 95% PI was − 5.242 to 6.590. “
“The dose of osteogenic supplement (OS) described in the section of cell culture system on page 103 contained errors. The corrected sentence appears below. This inner dish was placed into a 100-mm outer dish, and cultured in αMEM containing 10% fetal bovine serum and osteogenic supplement (OS) consisting of 5 mM β-glycerophosphate and 50 μM ascorbic acid under 5% CO2 and 20% O2.

Expression of the proneural bHLH transcription factor Ascl2

Expression of the proneural bHLH transcription factor Ascl2

is associated with stemness and is absolutely required for intestinal stem cell maintenance. Active Notch is required for Ascl2 expression and its loss results in precocious crypt cell differentiation [8 and 10]. The proneural protein Atoh1 acts as a master regulator of fate specification Birinapant of the secretory lineage [2 and 11]. Ascl2 expression is maintained by active Notch signalling that also acts to suppress Atoh1. Expression of Atoh1 is cell-autonomously inhibited by Hes proteins and in the absence of Notch signalling, crypt stem cells precociously differentiate into secretory goblet cells [7 and 12]. The spatial organisation of cells expressing Notch ligand and receptor in the crypt evokes a classic lateral inhibition scenario for control of stem versus secretory fate (Figure 2). Stem cells towards the crypt base found preferentially adjacent to Delta-expressing Paneth cells, express Notch receptor [13• and 14], signaling pathway and are maintained in an undifferentiated state by constant Notch signalling

and suppression of Atoh1 [7, 9, 15 and 16], As migrating cells lose contact with Paneth cells and the high Notch signalling they confer, they become poised between secretory and non-secretory fate. Lineage selection may then arise by stochastic variation in Delta expression leading some cells to express higher levels than others. This initial stochastic imbalance in Delta expression becomes reinforced allowing only a subset of cells (Delta high, Atoh high) rising up the crypt to become committed to a secretory fate while the rest become absorptive enterocytes. This regulation and functional organisation readily explains a binary fate in a supra-Paneth cell poised population but fits less well with a subsequent downstream cascade of secretory lineage choices specified after a series of cell divisions each progressing unidirectionally towards a more restricted fate. Moreover, recent evidence derived from regenerating systems casts doubt both on the existence of stable populations of

progenitors and the irreversibility of lineage specification. For many years it has also been known Metalloexopeptidase that intestinal regeneration following damage is not solely a function of surviving stem cells expanding to restore homeostasis (Figure 3) [17]. Following radiation induced injury the clonogenic fraction of crypt cells is elevated suggesting that these might correspond to the abundant and immature absorptive cells present within the early transit-amplifying compartment of the lower crypt. In support, specific ablation of the key Lgr5+ population using targeted diptheria toxin is not catastrophic as non-Lgr5+ cells (Bmi1+) cells are able to act as a replacement stem cell pool at least for a limited time [18].

“This article has been removed: please see Elsevier Policy

“This article has been removed: please see Elsevier Policy on Article Withdrawal ( This article has been removed at the request of the author. This abstract was inadvertently published in the journal when the authors

had requested that it should not. “
“Marijuana smoke is a complex mixture composed of thousands of chemical compounds, B-Raf inhibition many of which are qualitatively similar to those found in tobacco smoke (Moir et al., 2008). Like tobacco smoke, marijuana smoke has been associated with numerous adverse pulmonary effects in humans including airway inflammation, chronic bronchitis, edema, mucus hypersecretion, and the impairment of large airway function and lung efficiency (Lee and Hancox, 2011 and Tashkin, 2005). Moreover, Aldington et al. showed that the impairment of large airway function and lung efficiency is 2.5–5 times greater in marijuana

smokers than tobacco smokers (Aldington et al., 2007). Like tobacco smoke, previous studies have also shown marijuana smoke to be genotoxic both in vitro and in vivo (see Selleck Dapagliflozin Maertens et al., 2009 for a review). In addition, it is suspected that marijuana smoke may be carcinogenic. Indeed, some agencies such as the California Environmental Protection Agency have placed marijuana smoke on their list of chemicals known to cause cancer (Tomar et al., 2009). However, since there is a paucity of marijuana-only smoking populations to complete definitive studies, epidemiological studies conducted to date

are limited in scope, and often confounded by concurrent heptaminol tobacco smoking (Aldington et al., 2008, Hashibe et al., 2006, Sasco et al., 2002, Sidney et al., 1997 and Voirin et al., 2006). Therefore, a clear and widely accepted empirical link between marijuana smoking and cancer does not exist. Information on the pharmacokinetics of marijuana smoke, and the mechanisms by which it may cause adverse effects, is also limited. Several mechanisms have been proposed including genotoxicity (Ammenheuser et al., 1998, Busch et al., 1979, Chiesara et al., 1983, Leuchtenberger et al., 1973, Sherman et al., 1995, Stenchever et al., 1974, Vassiliades et al., 1986 and Wehner et al., 1980), alterations in endocrine function (Lee et al., 2006 and Lee et al., 2005), alterations in cell signaling pathways (Hart et al., 2004), and immune suppression (Baldwin et al., 1997, Massi et al., 2006 and Rieder et al., 2010). However, many of these findings are based on the testing of individual cannabinoids (e.g., Δ9-tetrahydrocannabinol, cannabinol, cannabidiol) found in marijuana smoke, as opposed to the whole smoke or smoke condensate. Genome-wide expression profiling may provide information to permit a better understanding of the toxicological pathways perturbed by exposure to marijuana smoke. Currently, there are no published studies that have used a whole genome toxicogenomics approach to evaluate responses to marijuana smoke. However, Sarafian et al.

Thus, this additional experiment rules out explanations of vestib

Thus, this additional experiment rules out explanations of vestibular-induced analgesia based on tactile gating of pain (Model 2), and confirms Model 1 (see Fig.

3A). This experiment further suggests that a common vestibular signal has projections to multiple independent somatic sensory systems, enhancing tactile perception and directly reducing acute pain perception. Although vestibular inputs produce no overt, recognizable conscious sensations, the vestibular system provides continuous information to the brain to maintain orientation in space (Angelaki and Cullen, 2008). A common vestibular input projects to multiple independent somatic sensory systems, directly increasing tactile perceptual processing, and directly decreasing perceptual processing of nociceptive stimuli. This finding provides new insights into the role of the vestibular Bortezomib in vivo system in buy DZNeP multisensory interactions, and in bodily awareness. Several multimodal sensory areas are known to receive both vestibular information and information from other modalities, notably vision and somatosensation (Faugier-Grimaud and Ventre,

1989). For example, functional imaging studies highlighted an anatomical overlap of vestibular and somatosensory projections in primary and secondary somatosensory cortices bilaterally (Bottini et al., 1994; Fasold et al., 2002; Emri et al., 2003). The bilateral modulations of touch and pain that we observed are consistent with this neuroimaging evidence. Our bilateral effects further suggest that the vestibular modulation of somatosensation may particularly Methamphetamine involve cortical areas whose neurons have bilateral somatosensory receptive fields, or strong transcallosal connections. The secondary somatosensory cortex is one such area (Iwamura et al., 1994). Interestingly, this area plays a major role in both

touch and pain perception (Ploner et al., 1999). A striking feature of vestibular multisensory interactions, therefore, is the specific independent modulation of distinct somatosensory submodalities. Decreases in tactile threshold demonstrate an up-regulation of tactile processing, while increases in pain threshold demonstrate a down-regulation of nociceptive processing. The pattern of correlation across participants between touch and pain effects suggests that both these modulations result from a common vestibular drive. Oculomotor and somatosensory effects of vestibular stimulation appeared to reflect a single latent factor. This view is also supported by a control experiment with nociceptive-specific laser stimulation. The vestibular system thus modulates connections with different somatosensory submodalities, regulating the activity in multiple sensory systems independently. Interestingly, human neuroimaging studies support this model, showing that vestibular stimulation both increases somatosensory cortex activations (Bottini et al., 1994, 1995; Bense et al., 2001; Fasold et al., 2002; Emri et al., 2003), but deactivates visual cortex (Bense et al., 2001).

The use of fluorescent labeling and fluorescent monitoring of the

The use of fluorescent labeling and fluorescent monitoring of the SE-HPLC peaks significantly increased the analytical sensitivity for measuring ATI, which can reach a concentration of 0.011 μg/mL, compared with the suboptimal concentration of 200–500 ng/mL achieved by bridging ELISA. Re-analysis of clinical samples which had previously tested positive using a bridging ELISA

method showed that 5% of them were negative using ATI-HMSA; otherwise, there was good correlation between the two assays on the ATI-positive samples. The false‐positive rate with the cut point of 1.19 μg/mL was 3%. However, this rate could be reduced by repeating the test if the result is within 10% of the cut point (i.e., 1.19–1.21 μg/mL). Additional patient samples are needed to verify the clinical utility of the ATI- and IFX-HMSA. Because a variety of anti-TNF drugs have been shown

to induce antibody formation in clinical studies (Bartelds et al., 2011, Karmiris et al., 2009 and Lichtenstein et al., 2010), the HMSA method may be applied to measure other antibody drug levels and anti-drug antibodies in patient serum samples. In conclusion, the liquid-phase HMSA methodology presented in this paper for the purpose of measuring ATI and IFX in IBD patient serum samples overcomes many limitations encountered in the solid-phase ELISA and RIA methods. Validation of the ATI- and selleck products IFX-HMSA also showed higher sensitivity and drug tolerance compared to that achieved by the ELISA method. This liquid-phase HMSA format is a useful platform that can be broadly applied to detect anti-drug antibodies and drug Montelukast Sodium levels for a variety of protein therapeutics during drug development and post-approval monitoring. All authors contributed to this study’s design, data collection, data analysis, and interpretation of data. All authors contributed to the writing of this manuscript and in the decision to submit the article for publication. All authors are employees of Prometheus Laboratories, Inc. This study and analyses were funded by Prometheus Laboratories, Inc. The

authors thank Dr. Emil Chuang, Dr. Reshma Shringarpure and Mr. Sami Shihabi for reviewing the manuscript. Writing support was provided by Drs. Rebecca Watson and Anthony Stonehouse of Watson & Stonehouse Enterprises, LLC and was funded by Prometheus Laboratories, Inc. “
“T cells play an important role in the protection against pathogens and cancer and have been shown to cause/contribute towards many autoimmune diseases (Wong and Pamer, 2003, Rudolph et al., 2006 and Bulek et al., 2012). The T cell receptor (TCR) recognizes foreign and self protein fragments bound to the self-major histocompatibility complex (pMHC) (Garboczi et al., 1996). The first structure of a murine TCR (2C) with MHC class I H2-Kb in association with dEV8 peptide was published in 1996 (Garcia et al., 1996).

G0900785 and by the Royal Society through the Paul Instrument Fun

G0900785 and by the Royal Society through the Paul Instrument Fund. The authors would

like to express appreciation to Clive Dixon, Mike Olsen, Ian Taylor, and Ian Thexton for fabrication of specialized glassware and equipment used in this work. The authors would like to also thank Prof. Ian Hall, and Prof. Peter Morris for useful discussions. A special thanks goes to Clémentine Lesbats for her assistance during the experiments. “
“By producing nuclear spin polarization far beyond that available at thermal equilibrium, hyperpolarization can provide improved sensitivity for NMR, enabling the detection of less concentrated molecules. In the area of molecular imaging, MRI has recently been used to study the distribution [1] and metabolism [2], selleck chemicals llc [3] and [4] of hyperpolarized substrates. For instance, multiple studies have reported on the conversion of hyperpolarized 13C-labeled pyruvate to its metabolic

products, alanine, lactate and carbonate in vivo [2], [3], [4], [5] and [6], in which higher lactate production is an important indicator of cancer. This technique is already being translated to the clinic and a first trial is ongoing [7]. Major hyperpolarization techniques include dynamic nuclear polarization (DNP) [8] and [9], spin exchange optical pumping polarization of noble gases [10] and parahydrogen induced polarization (PHIP) [11], [12], [13], [14], [15] and [16]. Parahydrogen is a spin isomer of hydrogen with an antisymmetric singlet spin state. By incorporating this pure spin state into a molecule through a hydrogenation reaction, STI571 in vitro large signal enhancements have been observed in a variety of situations as first conceived by Bowers

and Weitekamp [12] and Pravica and Weitekamp [14]. In 2009, Duckett’s group developed a parahydrogen polarization technique that works without the need for the chemical modification of the substrate [17]. In this approach, Etomidate the substrate and the parahydrogen bind to a catalyzing metal complex simultaneously, thus enabling polarization to be transferred to the substrate through the scalar coupling network. The polarized substrate is subsequently released, and replaced by new substrate which is polarized in turn. Such Signal Amplification By Reversible Exchange (SABRE) has already been applied to detect trace amounts of chemicals [18], [19] and [20] and used in conjunction with zero-field NMR spectroscopy [21]. According to a theoretical description of SABRE, the signal enhancement level depends on the binding kinetics and the magnetic field in which polarization transfer occurs [22]. In order to achieve better enhancement, new catalyst precursors have been developed to tune the binding kinetics. Enhancements can be boosted by using the bulky electron-donating phosphines of the Crabtree catalyst [23].

01) In contrast, comparing the effect of ATP depletion to that o

01). In contrast, comparing the effect of ATP depletion to that of BCRP inhibition ( Fig. 3B) showed that these two treatments caused similar changes to [3H]nifurtimox accumulation after 1, 2.5, 5 and 20 min, although it was noted that after 30 minutes ATP depletion caused a significantly greater increase (by 17–20%) in [3H]nifurtimox accumulation (p < 0.05). There

were no significant differences in [14C]sucrose accumulation between any treatments (data not shown). Probenecid (350 μM) was used to assess any initial contributions to [3H]nifurtimox and [14C]sucrose accumulation from proteins separate to P-gp and BCRP; namely multi-drug resistance associated BIBW2992 in vitro proteins (MRP) 1 and 2, organic anion-transporting polypeptides (OATPs) and organic anion transporters (OATs) (Table 1). Fig. 4 illustrates

the time dependent effect of probenecid on [3H]nifurtimox accumulation. This was not matched by the presence of 10 μM indomethacin, where no significant change to [3H]nifurtimox was observed at any time point. Taurocholic acid (TCA, 200 μM) and para-aminohippuric acid (PAH, 500 μM) were then Regorafenib mouse used to assess function of OATPs and OATs respectively. The addition of TCA caused significant changes in [3H]nifurtimox accumulation from 2.5 min (p < 0.01) and onwards when all three time-points showed significant increases (p < 0.001 Fig. 3), albeit less than those observed with the BCRP inhibitors. PAH caused no significant differences in accumulation of [3H]nifurtimox at any time point. No significant differences in [14C]sucrose accumulation between any treatments were observed (data not shown). With

CTs becoming the treatments of choice for HAT, the effect of their addition to the accumulation buffer was observed on [3H]nifurtimox and [14C]sucrose accumulation. The accumulation of [3H]nifurtimox in the hCMEC/D3s was not significantly affected by unlabelled melarsoprol (30 μM), whereas unlabelled pentamidine (10 μM) caused an increase at 2.5 min (p < 0.01) and this was maintained onwards to 30 min (p < 0.001), in comparison to DMSO controls ( Fig. 5A). The effect Oxaprozin of eflornithine (250 μM) and suramin (150 μM) on the accumulation of [3H]nifurtimox (without the presence of DMSO) saw no significant changes arise (Fig. 5B). There were no significant differences in [14C]sucrose accumulation between any of these treatments, or between DMSO and no DMSO controls (both [3H]nifurtimox and [14C]sucrose, data not shown). The potential of the compounds used in this study to cause cytotoxicity was assessed using an MTT assay and the effect compared to untreated control endothelial cells (hCMEC/D3) (Fig. 6). There were no significant differences on cell viability after 30 minutes exposure to the drugs, except when using the positive control 1% Triton X-100 (p < 0.01).

, 2001) In 1995, (Nobel et al (1995)) demonstrated that another

, 2001). In 1995, (Nobel et al. (1995)) demonstrated that another DC, pyrrolidine dithiocarbamate (PDTC), induces apoptosis in thymocytes by increasing the intracellular level of copper and, consequently, changing the redox activity in the medium, a similar result obtained here, but with relation with time and concentration of the DC. (Viquez et al. (2008)) suggested that DEDTC had the ability to accumulate copper, leading to lipid oxidation and damage with myelin inflammation in rats. Our studies showed that the cellular response was influenced by the DEDTC concentration with a non-linear accumulation of copper

Apoptosis inhibitor inside the cell. The effect of a higher DEDTC concentration that did not cause cell toxicity – as 25 μM – is a lower intracellular

copper accumulation than DEDTC at 5 μM, proving that copper content inside the cell can be responsible for the effects of DEDTC toxicity. Consequently, the intracellular accumulation of copper could generate oxidative stress with the formation of reactive oxygen species (ROS); many studies have reported the influence of copper on the formation of ROS in neuroblastoma cells that causes DNA damage (Arciello et al., 2005, Marengo et al., 2005, Gabbianelli et al., 1999 and Filomeni et al., 2007). Our results of the cell cycle studies (Fig. 2C) showed an increase in number of cells in the sub-G1 phase upon DEDTC treatment, confirming that the chelation caused some damage to cellular DNA. This result was confirmed by Annexin V/FITC and PI flow cytometry studies that showed an increase in the sub-G1 population selleck kinase inhibitor during the incubation with DEDTC, clearly indicating an apoptotic process (Fig. 3B). The tumor suppressor protein p53 is a transcription factor that regulates cell cycle progression and DNA repair in cells exposed to genotoxic

stress (Culmsee and Mattson, 2005). In many types of cells, the accumulation of p53 triggers apoptosis (Morrison et al., 2003 and Meulmeester and Jochemsen, 2008). Our results suggested that DEDTC induced the accumulation of p53 (Fig. 4) and, thus, triggered apoptosis in the SH-SY5Y cells. Apoptosis is regulated and executed by two main families of proteins, the Bcl-2 family and caspases (Aravind et al., 1999 and Hacker PRKD3 et al., 2011), and their activation can be initiated in two different ways, the extrinsic pathway (cytoplasmic) or the intrinsic pathway (mitochondrial). Our intention was to clarify the role of caspase 8 in p53-dependent apoptosis induced by DEDTC. Caspase 8 is a key upstream mediator in death receptor-mediated apoptosis and also participates in mitochondria-mediated apoptosis via the cleavage of proapoptotic Bid. In our studies, the observed activation of caspases 8 and 3 (Fig. 3A) and the unchanged levels of Bcl-2 (data not shown) suggested that the mechanism of DEDTC-induced apoptosis mainly involved the extrinsic pathway.