The ratio of the parietal to Occipital Values in right Plus left

The ratio of the parietal to Occipital Values in right Plus left hemispheres was significantly decreased. Correlation coefficients of the anterior

cingulate-primary sensorimotor, posterior cingulate-primary sensorimotor and occipital-media frontal in both hemispheres. of the frontal-primary sensorimotor, selleck products occipital-parahippocampal, primary visual-medial frontal and parahippocampal-amygdala in the right, and the frontal-vermis, parietal-thalamus, temporal-vermis, occipital-putamen, primary visual-putamen, thalamus-vermis and thalamus-cerebellum in the left were significantly different in patients compared with controls. Patients with late-onset depression who were treatment non-responders showed alterations not only in limbic-cortical circuits, but also in a wider network of thalamo-cortical circuits. (C) 2007 Elsevier Ireland Ltd. All rights reserved.”
“Background. The purpose of this double-blind randomized clinical trial was to compare the relative effectiveness of a higher protein and conventional carbohydrate intake during weight loss on body composition and physical function in older women.

Methods. Thirty-one overweight or obese, postmenopausal women (mean +/- SD: age 65.2 +/- 4.6 years, body mass index 33.7 +/- 4.9 kg/m(2)) were prescribed a

reduced calorie diet (1,400 kcal/day; 15%, 65%, 30% energy from protein, carbohydrate, and fat, respectively) Paclitaxel purchase and randomly assigned to 2 x 25 g/day whey protein (PRO n = 15) or maltodextrin (CARB n = 16) supplementation for 6 months. Lean soft tissue (LST) via dual-energy X-ray absorptiometry; thigh muscle, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue with magnetic resonance imaging; knee strength with isokinetic dynamometry; balance and physical function with a battery of performance tests.


PRO lost more weight than CARB (-8.0% +/- 6.2%, -4.1% +/- 3.6%, p = .059; respectively). Changes in LST, %LST, and strength, balance, or physical performance measures did not differ between groups (all p > .05). Weight to leg LST ratio improved more in PRO versus CARB (-4.6 +/- 3.6%, -1.8 +/- 2.6%, p = .03). PRO lost 4.2% more muscle (p = .01), 10.9% more SAT (p = .02), and 8.2% more intermuscular adipose tissue (p = .03) than CARB. Relative to thigh volume changes, PRO gained 5.8% more muscle (p = .049) and lost 3.8% greater SAT (p = .06) than CARB. Weight to leg LST ratio (r(2) = .189, p = .02) and SAT (r(2) = .163, p = .04) predicted improved up and go, relative muscle (r(2) = .238, p = .01) and SAT (r(2) = .165, p = .04) predicted improved transfer test, and %LST predicted improved balance (r(2) = .179, p = .04).


The RT-LAMP method is useful for the diagnosis of BEFV infection

The RT-LAMP method is useful for the diagnosis of BEFV infection in blood samples. (C) 2010 Published by Elsevier B.V.”
“Nitric oxide (NO)

is an important biomolecule for regulating various brain functions, such as the control Selleck Afatinib of neurovascular tone. NO, however, cannot be stored inside cells where NO is produced and immediately diffuses through the cellular membrane and decays rapidly, which makes the detection of NO extremely hard in an in vivo setting. We constructed an amperometric NO nanosensor and utilized it to directly measure NO release in the living brain. The NO nanosensor uses nanopores (pores with an opening radii <500 nm) in which NO is oxidized at the porous platinum surface. The nanopore-based sensor was inserted vertically into the brains of anesthetized mice up to the end of the hippocampal CA 3 region, or to a depth of about 3 mm. The sensor was slowly advanced in the 0.5 mu m increments and in 0.05 s temporal steps. Different levels of NO release were monitored by the nanopore NO sensor during the course of the penetration. selleck kinase inhibitor The hippocampal

CA3 region had the highest level of NO release, which was followed by CA2 and CA1 of the hippocampus and the cortex. The levels of NO release were not uniformly distributed within the cortical and hippocampal areas of living brain. In sum, the nanoporebased NO sensor was able to grossly measure NO contents within living brain in real time and with high sensitivity. This study may provide good insights about the relationship between the distributions of NOS-immunoreactive neurons and the directly measured levels of NO release in brain. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“The filoviruses, Marburg virus (MARV) and Ebola virus (EBOV), are causative agents of severe hemorrhagic fever with high mortality rates in humans and non-human primates. Sporadic outbreaks of filovirus infection have occurred in Central Africa and parts of Asia. Identification L-gulonolactone oxidase of the natural reservoir animals that are unknown yet and epidemiological investigations are current challenges to forestall outbreaks of filovirus diseases.

The filovirus species identified currently include one in the MARV group and five in the EBOV group, with large genetic variations found among the species. Therefore, it has been difficult to develop a single sensitive assay to detect all filovirus species, which would advance laboratory diagnosis greatly in endemic areas. In this study, a highly sensitive universal RT-PCR assay targeting the nucleoprotein (NP) gene of filoviruses was developed. The genomic RNAs of all known MARV and EBOV species were detected by using an NP-specific primer set. In addition, this RT-PCR procedure was verified further for its application to detect viral RNAs in tissue samples of animals infected experimentally and blood specimens of infected patients.

008) Protein C (35 +/- 10%, P = 008) and Factor V levels (28 +/

008). Protein C (35 +/- 10%, P = .008) and Factor V levels (28 +/- 20%, P = .008) were uniformly decreased, while d-dimers were elevated after repair in all patients BYL719 (310 +/- 213%, P = .008).

Conclusions. Leukocytosis and thrombocytopenia were uniform following endovascular TAAA repair, and the severity of the response correlated with post-operative renal dysfunction. Elevation of a sensitive marker of renal injury (NGAL) suggests that renal injury may occur in all patients after stent-graft insertion. (J Vasc Surg 2009;49:1140-6.)”
“Background: The rapid and reliable diagnosis of acute

myocardial infarction is a major unmet clinical need.

Methods: We conducted a multicenter study to examine the diagnostic accuracy of new, sensitive cardiac troponin assays performed on blood samples obtained in the emergency department from 718 consecutive patients who presented with symptoms suggestive of acute myocardial infarction. Cardiac troponin levels were determined in a blinded fashion with the use of four sensitive assays (Abbott-Architect Troponin

I, Roche High-Sensitive Troponin T, Roche Troponin I, and Siemens Troponin I Ultra) and a standard assay (Roche Troponin T). The final diagnosis was adjudicated by two independent cardiologists.

Results: Acute myocardial infarction was the Pevonedistat nmr adjudicated final diagnosis in 123 patients (17%). The diagnostic accuracy of measurements obtained at presentation, as quantified by the area under the receiver-operating-characteristic curve (AUC), was significantly higher with the four sensitive cardiac troponin assays than with the standard assay (AUC for Abbott-Architect Troponin I, 0.96; 95% confidence interval [CI], 0.94 to 0.98; for Roche High-Sensitive Troponin T,

0.96; 95% CI, 0.94 to 0.98; for Roche Troponin I, 0.95; 95% CI, 0.92 to 0.97; and for Siemens Troponin I Ultra, 0.96; 95% CI, 0.94 to 0.98; vs. AUC for the standard assay, 0.90; 95% very CI, 0.86 to 0.94). Among patients who presented within 3 hours after the onset of chest pain, the AUCs were 0.93 (95% CI, 0.88 to 0.99), 0.92 (95% CI, 0.87 to 0.97), 0.92 (95% CI, 0.86 to 0.99), and 0.94 (95% CI, 0.90 to 0.98) for the sensitive assays, respectively, and 0.76 (95% CI, 0.64 to 0.88) for the standard assay. We did not assess the effect of the sensitive troponin assays on clinical management.

Conclusions: The diagnostic performance of sensitive cardiac troponin assays is excellent, and these assays can substantially improve the early diagnosis of acute myocardial infarction, particularly in patients with a recent onset of chest pain. ( number, NCT00470587.)

N Engl J Med 2009;361:858-67.”
“Objective: To examine contemporary operative techniques and outcomes for repair of isolated iliac artery aneurysms.

Methods. We retrospectively reviewed the charts of all patients who underwent repair of an isolated iliac artery aneurysm from February 1995 to June 2007.

In contrast, Gairdner’s shrew-mice (Mus pahari) do express functi

In contrast, Gairdner’s shrew-mice (Mus pahari) do express functional XPR1. To determine whether Mus pahari could serve as a model for XMRV, primary Mus pahari fibroblasts and mice were infected with cell-free XMRV. Infection of cells in vitro resulted in XMRV Gag expression and the production of XMRV virions. After intraperitoneal injection of XMRV into Mus pahari mice, XMRV proviral DNA could be detected in spleen, blood, and brain. Intravenous administration of a green fluorescent protein (GFP) vector pseudotyped with XMRV produced GFP(+) CD4(+)

T cells and CD19(+) B cells. Mice mounted adaptive immune responses against XMRV, as evidenced by the production of neutralizing and Env- and Gag-specific buy A-1210477 antibodies. Prominent G-to-A hypermutations were also found in viral genomes isolated from the spleen, suggesting intracellular restriction of XMRV infection by APOBEC3 in vivo. These data demonstrate infection of Mus pahari by XMRV, potential cell tropism of the virus, and immunological and intracellular Captisol mw restriction of virus infection in vivo. These data support the use of Mus pahari as a model for XMRV pathogenesis and as a platform for vaccine and drug development against this potential human pathogen.”
“The first influenza pandemic of the new millennium was caused by a newly emerged swine-origin influenza virus (SOIV) (H1N1). This new virus is characterized

by a previously unknown constellation of gene segments derived from North American and Eurasian swine lineages and the absence of common markers predictive of human adaptation. Overall, human infections appeared to be mild, but an alarming number of young Oxalosuccinic acid individuals presented with symptoms atypical for seasonal influenza. The new SOIV also showed a sustained

human-to-human transmissibility and higher reproduction ratio than common seasonal viruses, altogether indicating a higher pathogenic potential for this newly emerged virus. To study the virulence of the SOIV, we used a recently established cynomolgus macaque model and compared parameters of clinical disease, virology, host responses, and pathology/histopathology with a current seasonal H1N1 virus. We here show that infection of macaques with two genetically similar but clinically distinct SOIV isolates from the early stage of the pandemic (A/Mexico/4108/2009 and A/Mexico/InDRE4487/2009) resulted in upper and lower respiratory tract infections and clinical disease ranging from mild to severe pneumonia that was clearly advanced over the mild infection caused by A/Kawasaki/UTK-4/2009, a current seasonal strain. Unexpectedly, we observed heterogeneity among the two SOIV isolates in virus replication, host transcriptional and cytokine responses, and disease progression, demonstrating a higher pathogenic potential for A/Mexico/InDRE4487/2009.

Further experiments were conducted using DCBPY in the Ru-NO2- con

Further experiments were conducted using DCBPY in the Ru-NO2- configuration. It was noted that the relaxation induced by DCBPY is completely blocked by the soluble guanylyl

cyclase (sGC) enzyme inhibitor. The non-selective K+ channel blocker (TEA) diminishes the potency of DCBPY, but it does not change the ME. Incubation with selective radicalar NO (NO center dot) and extracellular NO scavengers almost abolishes the relaxation induced by DCBPY. The use of a selective nitroxyl (NO-) scavenger decreases the potency of DCBPY, but it does not alter the ME. By using confocal microsopy, it was found that DCBPY, SNP, and NITRITE raise the cytosolic NO concentration and reduce the cytosolic Ca2+ concentration [Ca2+]c in rat aortic smooth muscle cells. These effects are not different when DCBPY and SNP are compared, but they buy VX-765 are lower for NITRITE. Taken together, our results demonstrate that the compound DCBPY (Ru-NO2-) is an NO generator that promotes relaxation of rat aortic rings due to a reduction in [Ca2+]c. The vascular smooth muscle relaxation is dependent on sGC activation. (C) 2011 Elsevier Inc. All rights reserved.”
“The response to high temperatures in adults of two cold stenothermal cave-dwelling leptodirins, Neobathyscia mandrill and Neobathyscia pasai

(Coleoptera, Cholevidae) was evaluated by determinating levels of gene expression of two members of the family of heat shock proteins 70 kDa by qPCR. In both species. hsc70 mRNA level was constant with increasing temperature, whereas a significant either increase in the inducible member (hsp70) mRNA was observed, higher in N. pasai. This difference could be due to their in-cave distribution: N. pasai

colonizes the cave entrance where the temperature is more variable than the internal part where N. mancinii is confined. These results demonstrated for the first time the occurrence of a heat shock response in troglobite insects and suggest the correlation between the intensity of this response and the adaptation to the cave environment. (C) 2011 Elsevier Ltd. All rights reserved.”
“Nitric oxide (NO) is an important biological messenger known to influence several types of human cancers. NO formation is catalyzed by three different nitric oxide synthase (NOS) enzymes. In this study we analyzed if the NOS3 promoter polymorphism -786T > C (rs2070744) and the NOS3 Glu298Asp polymorphism in exon 7 (rs1799983) influence risk and pathogenesis of urinary-bladder cancer. Allelic discrimination and DNA sequencing were used to determine the -786T > C and the Glu298Asp NOS3 genotypes in 359 urinary-bladder cancer patients, from a population-based patient material, and 164 population controls. Patient genotypes were combined with information on tumor stage, grade, stage and grade progression and cancer-specific death, using a 5-year clinical follow-up.

It is essential to direct efforts in patient-caregiver education

It is essential to direct efforts in patient-caregiver education to allow early recognition and management of all diabetic foot problems and Repotrectinib solubility dmso to build integrated pathways of care that facilitate timely access to limb salvage procedures. Increasing evidence suggests that the costs for implementing diabetic foot teams can be offset over the long-term by improved access to care and reductions in foot complications and in amputation rates. (J Vase Surg 2010;52:17S-22S.)”
“Background: The use of direct-to-consumer genomewide profiling to assess disease risk is controversial, and little is known about the effect of this technology

on consumers. We examined the psychological, behavioral, and clinical effects of risk scanning with the Navigenics Health Compass, a commercially available test of uncertain clinical validity and utility.

Methods: We recruited subjects from health and technology

companies AR-13324 order who elected to purchase the Health Compass at a discounted rate. Subjects reported any changes in symptoms of anxiety, intake of dietary fat, and exercise behavior at a mean (+/-SD) of 5.6+/-2.4 months after testing, as compared with baseline, along with any test-related distress and the use of health-screening tests.

Results: From a cohort of 3639 enrolled subjects, 2037 completed follow-up. Primary analyses showed no significant differences between baseline and follow-up in anxiety symptoms (P=0.80), dietary fat intake (P=0.89), or exercise behavior (P=0.61). Secondary analyses revealed that test-related distress was positively correlated with the average estimated lifetime risk among all the assessed conditions ((beta)=0.117, P<0.001). However, 90.3% of subjects who completed follow-up had scores indicating no test-related distress. There was no significant

increase in the rate of use of screening tests associated with genomewide profiling, most of which are not considered appropriate for screening asymptomatic persons in any case.

Conclusions: In a selected sample of subjects who completed follow-up after undergoing consumer genomewide testing, such testing did not result in any measurable short-term changes in psychological health, diet or exercise behavior, or use of screening 3-oxoacyl-(acyl-carrier-protein) reductase tests. Potential effects of this type of genetic testing on the population at large are not known. (Funded by the National Institutes of Health and Scripps Health.)

N Engl J Med 2011;364:524-34.”
“At the end of an anatomic peninsula, the foot in diabetes is prone to acute and chronic complications involving neuropathy, vasculopathy, and infection. Effective management requires an interdisciplinary effort focusing on this triad. In this article, we describe the key factors leading to foot complications and the critical skill sets required to assemble a team to care for them.

“OBJECTIVE: To evaluate the anatomic aspects of the diaphr

“OBJECTIVE: To evaluate the anatomic aspects of the diaphragma sellae and its potential role in directing the growth of a pituitary adenoma.

METHODS: Twenty cadaveric heads were dissected and measurements BI 10773 were taken at the level of the diaphragma sellae.

RESULTS: The diaphragma sellae is composed of two layers of dura mater. There is a remarkable variation in the morphology of the diaphragm opening. The average anteroposterior distance of the opening was 7.26 mm (range, 3.4-10.7 mm) and the average lateral-to-lateral distance was 7.33

mm (range, 2.8-14.1 mm).

CONCLUSION: The variability in the diameter of the opening of the diaphragma sellae could explain the growth of pituitary tumors toward the cavernous sinus or toward the suprasellar region.”
“Purpose: We studied whether the measurement of skin perfusion pressure (SPP) is useful for evaluating ischemic limbs and predicting wound healing.

Methods: Two hundred eleven patients (age range, 45 to 90 years; mean age, 69.6 +/- 9.2 years; 170 men and 41 women), 403 limbs with arteriosclerosis obliterans, were included in this study. Half of the patients had diabetes or were receiving dialysis or both.

Results. Significant correlations were found between SPP and ankle blood pressure (ABP), SPP and toe blood pressure (TBP), and SPP and the transcutaneous oxygen pressure (tcPO(2)) (P <.0001,

r = 0.75; P <.0001, r = 0.85; P <.0001, r = 0.62; respectively). In 94 limbs with ulcer or Fenbendazole gangrene, wound healing was predicted by the SPP. The mean SPP (mean +/- SD) in the healed-wound

group (25 limbs, 48 +/- 20 mm Hg) was greater than that in the unhealed-wound group (69 limbs, 23 +/- 11 mm Hg) (P <.001). According to the receiver operating characteristic (ROC) curve, the cut-off value of SPP was 40 mm Hg (sensitivity, 72%; specificity, 88%). Furthermore, we studied whether the combination of SPP and another measurement could predict wound healing more accurately than could any single variable. There was a strong correlation between SPP, TBP, and the healing rate (P <.001, r = 0.69) and healing could be accurately predicted if the SPP was greater than 40 mm Hg and if the TBP was greater than 30 mm Hg.

Conclusions: Our results suggest that measurement of SPP is an objective method for assessing the severity of peripheral arterial disease or for predicting wound healing.”
“OBJECTIVE: Ventricular shunting is a Common neurosurgical procedure. Metal-containing shunt components can cause artifacts on magnetic resonance imaging (MRI), obscuring visualization of the surrounding tissue. We present the case of a radiation-induced meningioma growing around a ventricular catheter that was not noted at an early stage as a result of artifact from an overlying shunt.

These data and computer-assisted structural study of the NoV caps

These data and computer-assisted structural study of the NoV capsid protein are compatible with a model of antigenic drift with tuning of the structure and functions of multiple proteins for the global outgrowth of new GII/4 variants. The availability of comprehensive information on genome sequences and unique protein changes of the recent global epidemic variants will allow studies of diagnostic assays, molecular epidemiology, molecular

biology, and adaptive changes of NoV in nature.”
“Transmembrane AMPA receptor regulatory proteins (TARPs), including gamma-2, gamma-3, gamma-4, and gamma-8, are auxiliary subunits for AMPA receptors. Based on studies in single knockout mice, it has been suggested that nearly all native AMPA receptors are associated with TARPs. To study the interplay between TARP family members and AMPA receptors in vivo, we generated AZD6244 datasheet mice lacking multiple TARPs. Triple knockout mice lacking gamma-3, gamma-4, and gamma-8 are viable and fertile, and synaptic AMPA receptor activity

is reduced to a level comparable to that seen in gamma-8 single knockout mice. In contrast, triple knockout mice lacking gamma-2, gamma-3, and either gamma-4 or gamma-8 cannot survive ex utero. In particular, gamma-2, gamma-3, gamma-4 triple knockout mice are born apneic and paralyzed, despite normal AMPA receptor function in cortical and spinal neurons. We found that gamma-8 is expressed at low levels in early postnatal mice and regulates AMPA receptor levels at this developmental time period. Thus, the early expression of gamma-8 may be responsible for maintaining AMPA receptor functions in neonatal neurons. Together, A 769662 our data indicate that TARPs, in particular gamma-2, are essential for early development, and that most neurons express multiple members of this functionally redundant protein family. (C) 2008 Elsevier Ltd. All rights

Liothyronine Sodium reserved.”
“Receptors are concentrated in the postsynaptic membrane but can enter and exit synapses rapidly during both basal turnover and processes of synaptic plasticity. How the exchange of receptors by lateral diffusion between synaptic and extrasynaptic areas is regulated remains largely unknown. We investigated the structural properties of the postsynaptic membrane that allow these movements by addressing the diffusion behaviors of AMPA receptors (AMPARs) and different lipids. Using single molecule tracking we found that not only AMPARs but also lipids, which are not synaptically enriched, display confined diffusion at synapses. Each molecule type displays a different average confinement area, smaller molecules being confined to smaller areas. Glutamate application increases the mobility of all molecules. The structure of the synaptic membrane is thus probably organized as a size exclusion matrix and this controls the rate of exchange of molecules with the extrasynaptic membrane. (C) 2008 Elsevier Ltd. All rights reserved.

The experimental factors included the congruency of request inter

The experimental factors included the congruency of request interpretation and the appropriateness of action selection. The results showed that brain regions including the right temporo-parieto-occipital (TPO) junction and the left

inferior parietal lobule (IPL) were more activated Ruxolitinib purchase when the interpretation of the requested object differed between the egocentric and allocentric perspectives than when it was the same (the effect of incongruency for consistency). On the other hand, greater activation was found in the right dorsolateral prefrontal cortex (DLPFC) when the incongruency effect was compared only between the conditions of appropriate action selection (the interaction effect). These results suggest that both the TPO junction and IPL are involved in obtaining visual information from the allocentric perspective when visual information based on only the egocentric perspective is insufficient SAHA HDAC datasheet to interpret another person’s request. The right DLPFC is likely related to this process to override the interference of action selection based on the egocentric perspective. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Many studies of hemispatial neglect patients have indicated that spatial attention

processes operate similarly in visual space and number space. However, some studies have indicated a dissociation of processing between visual line bisection and mental number bisection. A number of investigations have suggested that schizophrenic patients show a mild right pseudo-neglect on visual line bisection tasks. The present study was designed to determine if a functional link exists between performance of visual line and number line bisection in schizophrenic patients. Groups of 40 schizophrenic patients and 40 controls performed each bisection task. In the visual line bisection task, schizophrenic heptaminol patients showed a significant leftward bias relative to the healthy controls for 9 different line lengths. No significant difference in bias

was found between the 2 groups on the mental line bisection task. These results indicated that schizophrenic patients may exhibit attention deficit with respect to visual space but not number space, suggestive of the dissociation of processing between visual line bisection and mental number line bisection. These results provide more insight into the correlation between the visual line and number bisection tasks in schizophrenic patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Neuroimaging studies of individuals with posttraumatic stress disorder (PTSD) have revealed altered patterns of activity in medial prefrontal brain regions, including the anterior cingulate cortex (ACC), an area implicated in affect regulation. Selective serotonin reuptake inhibitors (SSRIs) have been shown to effectively treat PTSD symptoms, but there remains a lack of functional neuroimaging research examining the effects of psychopharmacological treatment on brain function in PTSD.

Pretreatment with antioxidants significantly blocked the copper-i

Pretreatment with antioxidants significantly blocked the copper-induced mPT by 48-75%. Copper (24 h) also caused a 30% reduction in ATP in astrocytes, which was completely blocked by CsA. Copper caused death (42%) in astrocytes by 48 h, which was reduced by antioxidants (35-60%) and CsA (41%). In contrast to astrocytes, copper did not induce mPT in neurons. Instead, it caused early and extensive death with a concomitant reduction (63%) in ATP by 14 h. Neuronal death was prevented by antioxidants and nitric oxide synthase inhibitors but not by CsA. Copper

increased protein tyrosine nitration in both astrocytes and neurons. These studies indicate that mPT, and oxidative and nitrosative stress Everolimus clinical trial represent major factors in copper-induced toxicity in astrocytes, whereas oxidative and nitrosative stress appears to play a major role in neuronal injury.”
“Artemisinin is the active principle of the Chinese herb Artemisia annua L. In addition to its anti-malarial activity, artemisinin and its derivatives have been

shown to exert profound anti-cancer Enzalutamide activity. The endoperoxide moiety in the chemical structure of artemisinin is thought to be responsible for the bioactivity. Here, we analyzed the cytotoxicity and the ability of artemisinin, five of its derivatives, and two other endoperoxides to inhibit generation of nitric oxide (NO). In the RAW 264.7 mouse macrophage cell line, the well-established model cell line to analyze NO generation, artesunate revealed the highest ability to inhibit NO production among all compounds tested. In cytotoxicity assays (XTT assay), the IC(50) value of RAW 264.7 cells for diglyceride artesunate was determined to be 3.1 +/- 0.7 mu M. In order to associate the cytotoxic effects with specific alteration in gene expression related to NO metabolism and signaling, whole genome mRNA microarray analyses were conducted. RAW 264.7 cells were treated with artesunate using DMSO as vehicle

control followed by microarray analysis. A total of 36 genes related to NO metabolism and signaling were found to be differentially expressed upon exposure to artesunate. Apart from NO-related genes, the expression of genes associated with other functional groups was also analyzed. Out of 24 functional groups, differential expression was most prominent in genes involved in cell-to-cell signaling and interactions. Further refinement of this analysis showed that the pathways for cAMP-mediated signaling and Wnt/beta-catenin signaling were most closely related to changes in mRNA expression. In conclusion, NO generation and signaling play a role in exhibiting cytotoxic activity of artesunate. In addition, other signaling pathways also contribute to the inhibitory effect of artesunate towards RAW 264,7 cells pointing to a multi-factorial mode of action of artesunate. (C) 2008 Elsevier Inc. All rights reserved.