A monoclonal antibody to alpha(2)-delta-1 revealed intense immunostaining in certain areas of rat brain, spinal cord, dorsal root ganglia, and skeletal muscle, with weaker staining in heart muscle, gut and liver. Little immunostaining was seen in spleen, kidney, thymus and lung. Staining was dense in some regions of the CNS including spinal dorsal horn anterior olfactory nucleus, anterior amygdala, basolateral (ventral)

amygdala and cortical amygdala, and the piriform, perirhinal, insular and entorhinal cortices. In hippocampus, staining Daporinad was heterogeneous with greater density in areas of glutamate terminals (mossy fiber endings on CA3 pyramidal cells and perforant path endings on granule cells and CA1 stratum radiatum). Moderate staining occurred in the lateral posterior nucleus of the thalamus, superficial layers of neocortex, periaqueductal CB-839 mw gray, substantia nigra, stria terminalis, nucleus accumbens shell and tegmental nucleus. We propose that areas of dense alpha(2)-delta-1 staining in brain and spinal cord are likely sites of action for the analgesic, anticonvulsant and anxiolytic-like actions of pregabalin and gabapentin in animal models. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Even though it is generally thought that umami stimuli such as monosodium glutamate (MSG) and sweet stimuli such as sucrose are

detected by different taste receptors, these stimuli appear to share taste qualities when amiloride

(a sodium channel blocker) is present to reduce PD-1/PD-L1 Inhibitor 3 order the sodium taste. Single fiber recording studies of the facial and glossopharyngeal nerves have shown that encoding Of L-2-amino-4-phosphonobutyrate (L-AP4), a potent mGluR4 agonist that elicits a taste quite similar to MSG, may occur in the same fibers that also encode sweet stimuli. This suggests that L-AP4 and sweet substances may activate common receptors or afferent signaling mechanisms. We report results of behavioral experiments that test this hypothesis. In the first study, rats conditioned to avoid sucrose or L-AP4 generalized the aversion to the opposite substance, indicating that both substances elicited similar tastes. However, two taste discrimination experiments showed that rats easily discriminated between sucrose and L-AP4 over a wide range of concentrations, even when the cue function of sodium associated with L-AP4 was reduced by amiloride and neutralized by adding equimolar concentrations of NaCl to sucrose. These data suggest that even though L-AP4 and sucrose elicit similar taste qualities, one or both substances also elicit other taste qualities not shared by the opposite substance. They also suggest that the taste-mGluR4 receptor and the signal pathway activated by L-AP4 are not the same as those activated by sucrose.

ECGs were classified as ischemic or nonischemic. The primary outcome was death at 1 year after the vascular operation. Independent predictors of long-term mortality were determined by Cox proportional hazards regression analysis.

Results: The most common vascular problem was an expanding abdominal aortic aneurysm (n = 185 [55%]). With regard to cTnI, 53 patients (16%) were classified as high (+) and 82 (24%) as low (+). The ECG in 21 patients (6%) showed evidence of myocardial ischemia. An increase in 1-year mortality of 3% for normal, 11% for low (+), and 17% for high (+) (P < .01) was seen with incremental

cTn values. Independent predictors of long-term mortality were age (odds ratio [OR], 1.05, 95% confidence interval [CI], 1.02-1.07; P < .01), stratified troponin (OR, 1.62; 95% see more CI, 1.25-2.10; Selleckchem Anlotinib P < .01), tissue loss (OR, 3.30; 95% CI, 1.72-6.33; P < .01), stratified

Revised Cardiac Risk Index (OR, 1.32; 95% CI, 0.97-1.81; P < .07), and statin use (OR, 0.62; 95% CI, 0.40-0.98; P = .04). The presence of ischemia on ECG was not a predictor of long-term mortality.

Conclusions: In the presence of an elevated cTn I, the ECG is not an independent predictor of long-term mortality after vascular surgery. These results support a strategy of routine surveillance of cTns after vascular surgery for the detection of cardiac events and postoperative risk stratification. (J Vasc Surg 2013;57:166-72.)”
“Luciferase exhibits a broad range of emitting frequencies. Light emission from the bioluminescence of luciferase makes it an excellent tool for monitoring selleck kinase inhibitor gene expression,

thus the control of its bioluminescence color has great bio-analytical applications. Here I use an elastic network model to examine how the sequence distribution of luciferase is related to bioluminescence multicolor emission. Based on the open and closed forms of crystal structures for luciferase, several computational analysis tools are applied to characterize the functionally relevant dynamical features within luciferase, and probe the dynamical mechanisms underlying the interactions between luciferin (a light-emitting substrate) and luciferase. Perturbation-based correlation analysis is used to identify hot-spot residues that are dynamically coupled to the active site of luciferase, and the results show that the sequence region of subdomain B of luciferase is largely responsible for determining the emitting color of bioluminescence. Moreover, the mode decomposition analysis reveals that the lowest frequency mode is the major contributor to the dynamical couplings between the hot-spot residues and the binding site in luciferase.”
“Objective: We examined the hypothesis that a 1 C reduction in body temperature would reduce gray and white matter injury induced by spinal cord ischemia in rats.

Some species of phospholipids were decreased in siRNA-treated cells. Cellular lipid droplets were evident and apoB secretion was decreased by 76% in these cells. Additionally, we discovered that ARPE-19 cells could synthesize and secrete

IWR-1 Apolipoprotein B100 (apoB100), which may serve as a backbone structure for the formation of lipoprotein particles in these cells. Our results indicate that FABP5 mRNA knockdown results in the accumulation of cellular triglycerides, decreased cholesterol levels, and reduced secretion of apoB100 protein and lipoprotein-like particles. These observations indicated that FABP5 plays a critical role in lipid metabolism in RPE cells, suggesting that FABP5 downregulation in the RPE/choroid complex in vivo might contribute to aging and early age-related macular degeneration. Laboratory Investigation (2010)

90, 906-914; doi:10.1038/labinvest.2009.33; published online 11 May 2009″
“Aims of the study. – Earlier P300 studies were conducted when the prevalence of dementia with Lewy Bodies (DLB) was unknown. Our study aims to examine whether P300 https://www.selleckchem.com/products/idasanutlin-rg-7388.html abnormalities are present in DLB and to evidence possible differences between DLB and Alzheimer’s disease (AD). A second aim of this study is to look for correlations between P300 recordings and EEG, as abnormal EEG variability has been described in DLB.

Patients and methods. – Auditory P300 responses were recorded by a classic oddball paradigm in 50 controls, in 36 DLB patients, and in 40 AD patients with MMSE > 20.

Results. – Reliable auditory P300 responses were obtained in 26 DLB (72%), 33 AD (82.5%), and 46 controls (92%). P300 was more delayed and had lower amplitude in DLB compared to AD groups. P300 topography was also different as the anterior-to-posterior scalp amplitude

gradient was reversed in DLB. P300 latency correlated with neuropsychological test scores and with EEG variables. Gradient inversion and delayed P300 responses in frontal Copanlisib nmr derivations evidenced differences between DLB and AD patients with a sensitivity of 70% and a specificity of 97%.

Conclusions. – P300 recordings are abnormal in DLB and can be useful to distinguish DLB from AD. (C) 2010 Elsevier Masson SAS. All rights reserved.”
“Differentiation and transformation of untransformed and ts-Src-transformed canine kidney MDCK cells in 2D and 3D environment were investigated using microarray technique, RT-PCR, confocal microscopy and functional assays. Activated Src induced epithelial-mesenchymal transition (EMT) in 2D environment followed by translocation of junctional proteins to the cytoplasm, without significant changes in protein expression.

Reduction of cAMP by the adenylyl cyclase inhibitor SQ22536 inhibited, and elevation of cAMP by forskolin, dibutyryl cAMP, IBMX and rolipram increased outgrowth and extension of neurites. The cAMP-mediated effects occur via activation of protein

kinase A (PKA) and Raf inhibitor were reduced by the inhibitors, H89 and Rp-cAMP. However, cAMP elevation did not lead to Erk activation that is an essential downstream component of neurotrophin signaling. These findings provide evidence for a key role of cAMP in promoting peripheral nerve regeneration after nerve injuries and indicate that this effect is unusual in not being mediated via Erk phosphorylation. (c) 2008 Published by Elsevier Ltd.”
“Purpose: High voltage activated calcium channels have been implicated in nociceptive transmission in several animal pain models. To our knowledge this is the first study to evaluate the ability of various high voltage activated calcium channel blockers to inhibit the transmission of

noxious stimuli from the bladder at the level of the spinal cord.

Materials and Methods: The nociceptive response was measured by analyzing the visceromotor reflex FG-4592 clinical trial and cardiovascular (pressor) responses to bladder distention. The role of Cav2.2 (N-type), Cav2.1 (P/Q-type) and Cav1 (L-type) calcium channels in bladder nociceptive reflex responses was examined using omega-conotoxin-GVIA, omega-agatoxin IVA/omega-conotoxin MVIIC and verapamil (Sigma-Aldrich (TM)), respectively. Female Sprague-Dawley rats were acutely instrumented with intrathecal catheters, carotid arterial and bladder cannulas. Needle electrodes were placed directly into the abdominal musculature to measure myoelectric activity subsequent

to repeat phasic bladder distention at 60 mm Hg for 30 seconds at 3-minute intervals with the rats under 1% isoflurane. Drugs were administered by intrathecal. injection 2 minutes before distention and responses were recorded for 15 minutes per dose.

Results: When administered intrathecally, omega-conotoxin-GVIA and omega-conotoxin MVIIC (10 mu g/kg each) significantly attenuated reflex responses to noxious bladder distention www.selleck.cn/products/ly2874455.html to 12% and 65% of the maximal visceromotor reflex response, and to 45% and 59% of the control pressor response, respectively. However, agatoxin and verapamil were less effective.

Conclusions: The study suggests that spinal Cav2.2 and Q-type Cav2.1 calcium channels contribute to acute bladder nociception, while Cav1 channels have a limited role.”
“Increasing evidences have been accumulated during recent years suggesting a role for antidepressant drugs (ADs) as hippocampal neurogenesis enhancers, but the information about the transductional mechanisms involved in this response is very limited.

Effects on atherothrombosis include the modulation of the expression of pro-atherogenic genes (e.g., endothelial leukocyte adhesion molecules, learn more inflammatory cytokines and cyclooxygenase (COX)-2) and the hepatic synthesis of very low density lipoproteins (VLDL), and are slow in onset, requiring incorporation into cell membrane phospholipids, and usually doses in humans in the order of 3g/day or higher. Effects on cardiac arrhythmias include complex interactions with ion channels (sodium, potassium and calcium channels), typically requiring the presence of free FA in extracellular fluids and usually occurring with lower doses (around 1 g/day) of nutritional or pharmacological intake. We have

focused most of our research effort in unraveling the pathophysiological background of protection by n-3 FA from atherothrombosis. As the result of incorporation of n-3 FA in the sn-2 position predominantly of the phosphatidyl ethanolamine click here pool in the inner leaflet of the plasma membrane, n-3 FA appear

on the one hand to increase the production of bioactive lipid mediators (protectins and resolvins) affecting cytokine-induced signal transduction; and on the other hand to directly interfere with the generation of reactive oxygen species (mostly hydrogen peroxide), directly responsible for the activation of the transcription factor nuclear factor (NF)-kappa B, which controls the expression of a variety of pro-inflammatory and pro-atherogenic

genes, including those encoding for interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)alpha, vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and COX-2. The upstream-direct or indirect-inhibition of cytokine- and other atherogenic trigger-induced signaling pathway may involve interference with the activation of protein kinase (PK) C isoforms and NADP(H) oxidase. Such interference may also explain the blunt anti-inflammatory effect of n-3 FA in many experimental models and clinical conditions of inflammation. All together, these mechanisms may provide an integrated view of how n-3 FA may affect CVD. (c) 2008 Elsevier Ltd. All rights reserved.”
“Bacteria have evolved diverse defense selleck chemicals llc mechanisms that allow them to fight viral attacks. One such mechanism, the clustered, regularly interspaced, short palindromic repeat (CRISPR) system, is an adaptive immune system consisting of genetic loci that can take up genetic material from invasive elements (viruses and plasmids) and later use them to reject the returning invaders. It remains an open question how, despite the ongoing evolution of attack and defense mechanisms, bacteria and viral phages manage to coexist. Using a simple mathematical model and a two-dimensional numerical simulation, we found that CRISPR adaptive immunity allows for robust phage-bacterium coexistence even when the number of virus species far exceeds the capacity of CRISPR-encoded genetic memory.

The PIPP score was significantly lower in infants given sucrose than in those given sterile water (mean 5.8, 95% CI 3.7-7.8 vs 8.5, 7.3-9.8; p=0.02) and significantly more infants had no change in facial expression after sucrose administration (seven of 20 [35%] vs none of 24; p<0.0001).

Interpretation Our data suggest that oral sucrose does not significantly affect activity in neonatal brain or spinal cord nociceptive circuits, and therefore might not be an effective analgesic drug. The ability of sucrose to

reduce clinical observational scores after noxious events in newborn infants should not be interpreted as pain relief.”
“Basal ganglia, an ensemble of interconnected subcortical

nuclei, are involved in adaptive motor planning and procedural learning. Striatum, the primary input nucleus selleck screening library of basal ganglia, extracts the pertinent cortical and thalamic information from background noise in relation with the environmental stimuli and motivation. The striatum comprises different neuronal populations: the GABAergic striatal output neurons, three classes of GABAergic interneurons and the cholinergic cells. Striatal learn more interneurons exert a powerful control of striatal output neuron excitability and therefore shape the cortico-basal ganglia information processing. Besides output neurons, striatal interneurons also receive directly cortical information and are able to adapt their behavior depending on the level of cortical and striatal activation. In this review, we focus on the corticostriatal long-term synaptic efficacy changes occurring in interneurons, and especially the spike-timing dependent plasticity

(STDP), as a Hebbian synaptic learning rule. Combined with the striatal local interactions between interneurons and output neurons, we will consider the functional consequences of the interneuron plasticity on the striatal output.

This article is part of a Special Issue entitled ‘Synaptic Plasticity & Interneurons’. (C) 2011 Elsevier Ltd. All rights reserved.”
“Background Clopidogrel and aspirin are the most commonly used antiplatelet therapies for percutaneous coronary intervention (PCI). We assessed the effect of various clopidogrel and aspirin regimens in prevention AZD8055 purchase of major cardiovascular events and stent thrombosis in patients undergoing PCI.

Methods The CURRENT-OASIS 7 trial was undertaken in 597 centres in 39 countries. 25 086 individuals with acute coronary syndromes and intended early PCI were randomly assigned to double-dose (600 mg on day 1, 150 mg on days 2-7, then 75 mg daily) versus standard-dose (300 mg on day 1 then 75 mg daily) clopidogrel, and high-dose (300-325 mg daily) versus low-dose (75-100 mg daily) aspirin. Randomisation was done with a 24 h computerised central automated voice response system.

Furthermore, the high ALDH1A1 expression in PCa was positively correlated with Gleason score (P = 0.01) and pathologic stage (P = 0.01), and inversely associated with overall survival and cancer-specific survival of the patients (P = 0.00093 and 0.00017, respectively). ALDH1A1 could be a prostate CSC-related marker. Measuring its expression

might provide a potential approach to study tumorigenesis of PCa and predict outcome of the disease. Laboratory Investigation (2010) 90, 234-244; doi:10.1038/labinvest.2009.127; published online 14 December 2009″
“Pyrethroids are one of the most widely used class of insecticides and A-1210477 clinical trial their toxicity is dominated by pharmacological actions upon the CNS. This study reports as the subchronic treatment (60 days) with permethrin (PERM) (1/10 of LD(50)) induced nuclear DNA damage in rat striatum cells. Comet assay outcomes showed that PERM produced single- and double strand breaks in striatum cells, the DNA damage was not related to oxidation at pyrimidine and purine bases. Vitamin E (280 mg/kg body weight/day) and vitamin E+coenzyme Q(10) (10 mg/kg/3 ml) supplementation could protect PERM treated rats against nuclear DNA damage.

With the aim to evaluate the cause of nuclear DNA damage observed in striatum of rat treated with PERM, in vitro studies on striatum submitochondrial Selleckchem Elafibranor particles (SMPs) and on striatum cells treated with 10 mu M PERM alone or plus 16 or 32 nM

GSH were performed. SMPs incubated with PERM showed a decrease in superoxide anion release from the electron transport chain by inhibition of mitochondrial complex I. The effect could be related to the decrease of membrane fluidity Tacrolimus (FK506) measured in the hydrophilic-hydrophobic region of the mitochondrial membrane. This result discarded the involvement of the mitochondrial reactive oxygen species in the nuclear DNA damage. On the contrary, GSH played a crucial role on striatum since it was able to protect the cells against nuclear DNA damage induced by PERM. In conclusion our outcomes suggested that nuclear DNA damage of striatum cells was directly related to GSH depletion due to PERM insecticide. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Fatty liver disease has become a health problem related to metabolic syndrome worldwide, although its molecular pathogenesis requires further study. It is also unclear whether advanced fibrosis of steatohepatitis will regress when diet is controlled. The aim of this study was to investigate whether the resolution of fibrosis occurs in steatohepatitis induced by a methionine-choline-deficient diet (MCDD). Manifestation of endoplasmic reticulum (ER) stress in this model was also studied. Nonalcoholic steatohepatitis with advanced fibrosis was induced in rats by feeding them an MCDD for 10 weeks.

We calculate a putative age for coalescence of similar to 180,000 to 200,000 years ago, which is consistent with previous mitochondrial DNA-based estimates.”
“Regulatory T cells (T-regs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate T-reg responses. Because

neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist SB202190 research buy that regulate the number and function of colonic T-regs. We determined that short-chain fatty acids, gut microbiota-derived bacterial learn more fermentation

products, regulate the size and function of the colonic T-reg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.”
“Background: Most studies on granulosa cell (GC) function in cattle have been performed using GC and follicular fluid (FF) samples collected from slaughterhouse ovaries. Using this approach, the follicular developmental stage and functional status are unknown and indirectly inferred, limiting data interpretation. Ultrasound-guided follicle aspiration has previously been used to recover S3I-201 cell line GC or FF samples, but this was mostly carried out in large follicles or pools of small follicles, without recording the efficiency of recovery. The present study was aimed at adapting and evaluating an ovum pick-up (OPU) system for the in vivo recovery of FF and GC from individual follicles of different diameters.

Methods: In the first trial, the losses of fluid inside the tubing system were calculated using a conventional or an adapted-OPU system. Blood plasma volumes equivalent to the amount of FF in follicles of different diameters were aspirated

using a conventional OPU Teflon circuit. The OPU system was then adapted by connecting 0.25 mL straws to the circuit. A second trial evaluated the efficiency of FF recovery in vivo. Follicles ranging from 4.0 to 16.8 mm in diameter were aspirated individually using the conventional or adapted-OPU systems. A third trial assessed the in vivo recovery of GC and the subsequent amount of RNA obtained from the follicles of different diameters from Holstein and Gir cattle.

Results: In Trial I, the plasma recovery efficiency was similar (P > 0.05) for the volumes expected for 12 and 10 mm follicles, but decreased (P < 0.05) for smaller follicles (45.7+/-4.0%, 12.4+/-4.3% and 0.0+/-0.0% for 8, 6, and 4 mm follicles, respectively). Using the adaptation, the losses intrinsic to the aspiration system were similar for all follicle diameters.

348 patients reached the primary endpoint (A-002 n=278, placebo n=70). Mean sPLA,-IIA concentration fell by 86.7%, from 15 . 7 pmol/L to 2 . 1 pmol/L, in the overall active treatment group, and by 4.8%, from 15.7 pmol/L to 14.3 pmol/L, in the placebo group (p<0.0001 treatment vs placebo). The reductions in sPLA(2)-IIA concentration in the A-002 groups

were dose dependent (ranging from 69.2% in the 50 mg group to 95.8% in the 500 mg group) and differed significantly from placebo (p<0 . 0001 for all doses). In the 500 mg A-002 treatment group, there was one serious adverse event (exacerbation of underlying chronic obstructive pulmonary disease), but the proportion of patients reporting treatment-emergent adverse events

did not differ from placebo. The main side-effects of the drug included headache (n=20), nausea (n=17), and buy Givinostat diarrhoea (n=12).

Interpretation The reductions in sPLA(2)-IIA concentration suggest that A-002 might be an effective anti-atherosclerotic agent.

Funding Anthera Pharmaceuticals.”
“Rheumatoid arthritis is a systemic, inflammatory, autoimmune disorder. Enhanced understanding of molecular pathogenesis has enabled development of innovative biological agents that target specific parts of VE 822 the immune system. These treatments have changed the course and face of rheumatoid arthritis and outcomes for patients and society New knowledge has emerged of how environmental factors interact with susceptibility genes and the immune system in the pathogenesis of a major subset of rheumatoid arthritis. Research

undertaken on the longitudinal disease process and molecular pathology of joint inflammation has led to new therapeutic strategies that promote early use of disease-modifying drugs with tight disease control and distinct and quantifiable treatment goals. Today, such approaches can halt most cases of joint destruction but not all instances of joint inflammation and comorbidity Understanding the cause and pathogenesis of different rheumatoid arthritis subsets will selleck chemicals llc lead not only to individualised treatments during early phases of the illness but also, possibly, to disease prevention.”
“The stimulation of a tumour-specific T-cell response has several theoretical advantages over other forms of cancer treatment. First, T cells can home in to antigen-expressing tumour deposits no matter where they are located in the body-even in deep tissue beds. Additionally, T cells can continue to proliferate in response to immunogenic proteins expressed in cancer until all the tumour cells are eradicated. Finally, immunological memory can be generated, allowing for eradication of antigen-bearing tumours if they reoccur. We will highlight two direct methods of stimulating tumour-specific T-cell immunity: active immunisation with cancer vaccines and infusion of competent T cells via adoptive T-cell treatment.

“
“Quality by design (QbD) has been receiving a lot of attention in the pharmaceutical community of late. Successful QbD implementation requires a thorough Elafibranor order understanding of the relationship between the critical quality attributes (CQAs) and the clinical properties of the product, the relationship between the process and CQAs and the variability in raw materials. This article presents a roadmap for successful QbD implementation for therapeutic biotechnology products. The approach presented here

is aligned with existing regulatory guidance documents. Key developments are reviewed and case studies are used to illustrate these concepts. It is concluded that although several QbD concepts are being practiced PRT062607 manufacturer by the biotechnology industry, successful dialogue and partnership between the industry and its regulators will be the key to successful QbD implementation.”
“Over-activation of N-methyl-D-aspartate (NMDA) receptors is critically involved in many neurological conditions, thus there has been considerable interest in developing NMDA receptor antagonists. We have recently identified a series of naphthoic and phenanthroic acid compounds that allosterically modulate NMDA receptors through a novel mechanism of action. In the present study, we have determined the structure-activity

relationships of 18 naphthoic acid derivatives for the ability to inhibit the four GluN1/GluN2(A-D) NMDA receptor subtypes. 2-Naphthoic acid has low activity at GluN2A-containing receptors and yet lower activity at other NMDA receptors. 3-Amino addition, and especially 3-hydroxy addition, to 2-naphthoic acid increased inhibitory activity at GluN1/GluN2C and GluN1/GluN2D receptors. Further halogen and phenyl substitutions to 2-hydroxy-3-naphthoic acid leads to several relatively potent inhibitors, the most potent of which is UBP618 (1-bromo-2-hydroxy-6-phenylnaphthalene-3-carboxylic

learn more acid) with an IC50 similar to 2 mu M at each of the NMDA receptor subtypes. While UBP618 is non-selective, elimination of the hydroxyl group in UBP618, as in UBP628 and UBP608, leads to an increase in GluN1/GluN2A selectivity. Of the compounds evaluated, specifically those with a 6-phenyl substitution were less able to fully inhibit GluN1/GluN2A, GluN1/GluN2B and GluN1/GluN2C responses (maximal % inhibition of 60-90%). Such antagonists may potentially have reduced adverse effects by not excessively blocking NMDA receptor signaling. Together, these studies reveal discrete structure-activity relationships for the allosteric antagonism of NMDA receptors that may facilitate the development of NMDA receptor modulator agents for a variety of neuropsychiatric and neurological conditions. (c) 2011 Elsevier Ltd. All rights reserved.