Both open loop and feedback operative mode are described and achi

Both open loop and feedback operative mode are described and achieved results are presented. (C) 2010 American Institute of Physics. [doi: 10.1063/1.3360773]“
“Background: Reduction of HIV-1 breast-feeding transmission remains a challenge for prevention of pediatric infections

in Sub-Saharan Africa. Provision of formula decreases transmission but often increases child mortality in this setting.

Methods: A prospective observational cohort study of HIV-1 exposed infants of mothers receiving pre and postnatal medical care at Drug Resource Enhancement Against AIDS and Malnutrition centers in Mozambique was conducted. Live-born infants of HIV-1-infected women Talazoparib receiving medical care were enrolled, HIV-1 testing was performed at 1, 6, and 12 months of age using branched DNA. Mothers were counseled to breast-feed exclusively for 6 months

and were provided HAART antenatally mid postnatally for the first 6 months. Women with CD4 cell counts less than 350/cmm at baseline continued HAART indefinitely.

Results: Of 341 infants followed from birth, 313 mother-infant pairs (92%) completed 6 months and 283 (83%) completed 12 months of follow-up. HIV-1 diagnosis was ascertained in 287 infants (84%) including 4 who died. There were 9 cases of HIV-1 transmission: 4 of 341 (1.2%) at 1 S3I-201 month, 2 of 313 (0.6%) at 6 months, and 2 of 276 (0.7%) at PFTα 12 months (cumulative rate: 2.8%). Two mothers (0.6%) and 11 infants (3.2%) died. Maternal and infant mortality rates were 587 of 100,000 and 33 of 1000, while country rates are 1000 of 100,000 and 101 of 1000. HIV risk reduction was 93% and HIV-free survival at 12 months was 94%.

Conclusions: Late postnatal transmission of HIV-1 is significantly decreased by maternal use of HAART with high infant survival rates up to 12 months of age.”
“In order to compare multidimensional fatigue research findings across age and gender subpopulations, it is important to demonstrate measurement invariance, that is, that the items from an instrument have equivalent

meaning across the groups studied. This study examined the factorial invariance of the 18-item PedsQL (TM) Multidimensional Fatigue Scale items across age and gender and tested a bifactor model.

Multigroup confirmatory factor analysis (MG-CFA) was performed specifying a three-factor model across three age groups (5-7, 8-12, and 13-18 years) and gender. MG-CFA models were proposed in order to compare the factor structure, metric, scalar, and error variance across age groups and gender. The analyses were based on 837 children and adolescents recruited from general pediatric clinics, subspecialty clinics, and hospitals in which children were being seen for well-child checks, mild acute illness, or chronic illness care.

The objective of this study was to describe the characteristics a

The objective of this study was to describe the characteristics and prognostic value of cough in IPF.


Subjects with IPF were identified from an ongoing longitudinal database. Cough and other clinical variables were recorded prospectively. Logistic regression was used to determine predictors of cough and predictors of disease progression, defined as 10% decline in FVC, 15% decline in DLCO, lung transplantation or death within 6 months of clinic visit. The relationship of cough with time to death or lung transplantation was analysed using Cox proportional hazards analysis.

Results: Two hundred and forty-two subjects were included. Cough was reported in 84% of subjects. On multivariate analysis, cough was less likely in previous smokers (OR 0.07, 95% CI: 0.01-0.55,

P = 0.01), and more likely in subjects with exertional this website desaturation (OR 2.56, 95% CI: 1.15-5.72, P = 0.02) and lower FVC (OR 0.76, 95% CI: 0.60-0.96, P = 0.02). Cough predicted disease progression (OR 4.97, 95% CI: 1.25-19.80, P = 0.02) independent Z VAD FMK of disease severity, and may predict time to death or lung transplantation (HR 1.78, 95% CI: 0.94-3.35, P = 0.08).

Conclusions: Cough in IPF is more prevalent in never-smokers and patients with more advanced disease. Cough is an independent predictor of disease progression and may predict time to death or lung transplantation.”
“OBJECTIVES: To evaluate the histological changes of tracheal cartilage and epithelium caused by tracheal occlusion at different gestational ages in a fetal rat model.

METHODS: Rat fetuses were divided into two groups: a) External control, composed of non-operated rats, and b) Interventional group, composed of rats operated upon on gestational day 18.5 (term = 22 days), divided into triads: 1) Tracheal occlusion, 2) Internal control and 3) Sham (manipulated but not operated). Morphological

data for body weight, total lung weight and total lung weight/body weight ratio were collected and measured on gestational days 19.5, 20.5 and 21.5. Tracheal samples were histologically processed, and epithelial, chondral and total tracheal thicknesses were measured on each gestational day.

RESULTS: The tracheal occlusion group exhibited an increase in total lung weight/body weight ratio (p<0.001). Histologically, this group had a thicker epithelial thickness (p<0.05) and thinner chondral (p<0.05) and total tracheal thicknesses (p<0.001). These differences were more prominent on gestational days 20.5 and 21.5.

CONCLUSION: Tracheal occlusion changed tracheal morphology, increased epithelial thickness and considerably decreased total tracheal thickness. These changes in the tracheal wall could explain the development of tracheomegaly, recently reported in some human fetuses subjected to tracheal occlusion.”
“Grape seed extract (GSE) was encapsulated in biocompatible poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) using the solution enhanced dispersion by supercritical fluids (SEDS) technique.

Copyright (C) 2011 S Karger AG, Basel”
“After a decade of i

Copyright (C) 2011 S. Karger AG, Basel”
“After a decade of intensive

investigation but only few replicable results, Alzheimer’s disease (AD) genetics research is slowly picking up pace. This is mostly owing to the completion of several genome-wide association studies (GWAS), which have suggested the existence of over three dozen potential new AD susceptibility genes. Although only a handful of these could be confirmed in subsequent independent replication efforts to date, this success rate is still much higher than in the pre-GWAS era. This review provides a brief summary of the principal methodologic advances in genetics research of the past decade, followed by a description of the most compelling findings that these advances have unearthed in AD. The paper closes

with a discussion Selleckchem OSI-027 of the persistent methodologic difficulties and challenges and an outlook on what we can expect to gain from the next 10 years of AD genetics research.”
“Purpose: To compare the clinical and imaging features of posttransplantation lymphoproliferative disorder (PTLD) in pediatric patients who underwent hematopoietic cell transplantation with those in pediatric patients who underwent liver transplantation.

Materials BI2536 and Methods: This study was approved by the institutional review board, and the requirement to obtain informed consent was waived. The authors retrospectively reviewed the medical records and images of 552 hematopoietic cell transplant A-769662 solubility dmso recipients and 195 liver transplant recipients. PTLD was histopathologically confirmed in 17 of the patients who underwent hematopoietic cell transplantation and 27 of the patients who underwent liver transplantation. The overall frequency, clinical course, histopathologic type, and imaging findings of PTLD were compared between the two patient groups by using the Fisher exact test.

Results: The overall frequency of PTLD was 3% (17 of 552 patients) after hematopoietic

cell transplantation (12% [nine of 75 patients] after umbilical cord blood transplantation) and 14% (27 of 194 patients) after liver transplantation. PTLD occurred within 6 months of transplantation in 14 of the 17 hematopoietic cell recipients (82%) and 11 of the 27 liver recipients (41%) (P = .012). Histopathologic examination revealed monomorphic disease in 11 of the 17 hematopoietic cell recipients (65%) and eight of the 27 liver recipients (30%) (P = .031). The abdomen was the most common site of involvement in both groups. Extraabdominal PTLD developed in 12 of the 17 hematopoietic cell recipients (71%) and five of the 27 liver recipients (19%) (P = .002). Although 15 of the 17 patients with hematopoietic cell transplantation-related PTLD (88%) exhibited responses after treatment, the overall mortality rate was 35% (six of 17 patients). All 27 patients with PTLD after liver transplantation improved after treatment and remain alive.

In addition, we find that for these solids under given surface el

In addition, we find that for these solids under given surface electromigration conditions, the morphological response of their < 111 >-oriented surfaces is superior

to that of their < 100 >-oriented and < 110 >-oriented surfaces. Furthermore, we demonstrate that increasing the strength of the surface diffusional anisotropy in these materials has beneficial effects on their Trichostatin A research buy surface morphological stability under the simultaneous action of an electric field. Our predictions can provide guidance for experimental studies of surface morphological response to the combined action of electric fields and mechanical stresses, as well as for tailoring operating conditions to improve the mechanical reliability of thin films in service. (C) 2010 American Institute of Physics. [doi: 10.1063/1.3393965]“
“Medication overuse headache (MOH) is now recognized as a biobehavioral disorder, a condition wherein emotion and pain are intermingled. This review discusses the steps to consider when treating this condition. The first step involves educating patients PCI32765 about MOH and the pathways to chronicity. The second step concerns working with patients to identify risk factors and behaviors that are present and contributing to the condition. The final step involves behavioral

intervention. Examples for accomplishing each step are provided.”
“This paper describes the inhibitory activities of diacylglyceride phospholipids, such as phosphatidylcholine (lecithin), phosphatidylethanolamine (cephalin), phosphatidylserine, phosphatidylglycerol, bisphosphatidylglycerol

(cardiolipin), phosphatidylinositol, and phosphatidic acid (phosphatidate) (compounds 1-7, respectively) against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds selleck chemicals llc tested, compounds 3-7 were revealed to be potent inhibitors of animal pols: compound 4 was the strongest inhibitor, with IC(50) values for different pols of 1.7 – 15 mu M. Compounds 4-7 also inhibited the activity of human topo II: compound 7 was the strongest inhibitor, with an IC(50) value of 20 mu M. The glycerophospholipids had no effect on the activities of plant (cauliflower) pol alpha, prokaryotic pols, or other DNA metabolic enzymes, such as calf primase of pol alpha, T7 RNA polymerase, T4 polynucleotide kinase, and bovine deoxyribonuclease I. These results suggest that compounds 4-7 are selective inhibitors of animal pols and human topos. Compounds 4 and 7 also suppressed the growth of a human colon carcinoma cell line that lacked p53 (HCT116 p53(-/-)); their LD(50) values were 63.6 and 51.1 mu M, respectively, suggesting that cell growth inhibition by these compounds leads to the inhibition of pols and/or topos. From these findings, diacylglyceride phospholipids, which are present in various foods, might be effective nutrients for promoting human anti-cancer health promotion.

8 +/- 9 5) with at least four 3-mm or larger macular SK on one ex

8 +/- 9.5) with at least four 3-mm or larger macular SK on one extremity, neck, or chest were enrolled and provided informed consent. Subjects received three treatments at 3- to 4-week intervals. Subjects were treated at settings of 10 to 20 similar to mJ with 30% to 55% surface area coverage and four to eight passes at each session. Investigators performed a global extremity SK count, an SK count within a 5- by 5-cm (25 similar to cm2) square on transparency mapping, and lesion thickness

grading. Side effects were assessed. Patients rated pain using a visual analog scale. Results At baseline, average global SK count was 43.2 +/- 27.3. At 1-month follow-up, 20.7 +/- 16.6 lesions remained. At 3- and 6-month follow-up, 17.7 +/- 23.8 and 14.7 +/- 18.6 lesions remained, respectively. A decrease in

thickness and SK counts within the 5- CHIR 99021 by 5-cm square was also observed. Moderate erythema and mild edema were post-treatment responses. Conclusion Nonablative fractional click here resurfacing using the 1927-nm thulium fiber laser is a safe and effective treatment modality to decrease nonfacial macular SK.”
“Study Design. Clinical and radiologic assessment derived from a prospective multicenter data base of adolescent idiopathic scoliosis (AIS) patients.

Objective. We investigated if “”implant density”" or the number of screws correlated with the major curve (thoracic or lumbar) correction at 2 years in patients with AIS. We also investigated the effect of implant density on the change in sagittal contour before surgery to after surgery.

Summary of Background Data. Controversy exists regarding number and type of spinal anchors and the number of implant sites used that result in improved correction in AIS.

Methods. A prospective database of patients with AIS treated by posterior instrumentation between 1995 and 2004 was analyzed. The major curve correction expressed

as % correction (from preoperative to 2 years postoperative) High Content Screening was correlated with the percentage of implants relative to the number of available implant sites within the measured Cobb angle. Correlation of % correction to the number of hooks, wires, and screws was also performed. We also analyzed the change in sagittal contour T2-T12, T5-T12, and T10-L2 before surgery and after surgery. This absolute change was then correlated with implant density, as was the number of hooks, wires, and screws.

Results. There were 292 patients included with all 6 Lenke curve types represented (250 with major thoracic curves and 42 with major lumbar curves). The overall % coronal Cobb correction was 64% (range: 11%-98%). The implant density within the major curve averaged 61% (range: 6%-100%). There was a significant correlation between implant density and % curve correction (r = 0.31, P = 0.001).

This work should inform and assist researchers undertaking or pla

This work should inform and assist researchers undertaking or planning similar studies in Indigenous and developing populations.”
“FOXO4 constitutes a coherent candidate gene associated with premature ovarian failure (POF) pathogenesis. This study sequenced the coding and exon-flanking regions of this gene in a panel of 116 POF patients and 143 controls of

Tunisian origin. In both groups, the IVS2 + 41T > G sequence variant was identified. It is concluded that coding mutations of FOXO4 should not be a common cause of the disease in women PU-H71 Cytoskeletal Signaling inhibitor from the Tunisian population. However, this study cannot exclude that FOXO4 dysfunctions, originated from open reading frame or promoter sequence variations, might be associated with the

pathogenesis of selleck kinase inhibitor the disease in other ethnical groups. (C) 2011, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.”
“C-reactive protein (CRP) levels vary remarkably with ethnic status. Its distribution and correlates should be investigated across diverse populations, and these were limited in a representative Chinese population. We investigated 3133 participants aged 18-80 years in Shanghai, which were sampled using a randomized, stratified, multi-stage sampling method. The distribution of CRP was highly skewed toward a lower level. The median CRP was 0.55 mg/L (0.61 mg/L in males, 0.51 mg/L in females). Participants living in urban region had higher CRP levels than those in rural region (0.67 vs. 0.46 mg/L). CRP levels showed significant correlation with traditional cardiovascular risk factors, buy ACY-738 and it was most strongly correlated with body mass index. Multivariate logistic

regression analyses indicated that elevated CRP (being in the top 15 percentile of CRP; CRP >= 2.09 mg/L) was significantly associated with obesity, hypertension, diabetes, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, high triglycerides and cardiovascular disease history. In conclusion, the distribution of CRP in adult Chinese was comparable with that of many other Asian populations but different from that of Western populations. Metabolic impairment was associated with elevated CRP, and CRP levels should be interpreted in conjunction with the lipid profile.”
“Early life stress (ELS) in rodents has profound long-term effects that are partially mediated by changes in maternal care. ELS not only induces “”detrimental”" effects in adulthood, increasing psychopathology, but also promotes resilience to further stressors. In Long-Evans rats, we evaluated a combination of two procedures as a model of ELS: restriction of bedding during the first post-natal days and exposure to a “”substitute”" mother. The maternal care of biological and “”substitute”" mothers was measured. The male and female offspring were evaluated during adulthood in several contexts.

However, it is not known whether each plant species requires both

However, it is not known whether each plant species requires both of these two types of molecules for chitin signaling, nor the relationships between these molecules in membrane signaling. We report here that rice cells require a LysM receptor-like kinase, OsCERK1, in addition to CEBiP, for chitin signaling. Knockdown of OsCERK1 resulted in marked suppression of the defense responses induced by chitin oligosaccharides, indicating that OsCERK1 is essential for chitin signaling in rice. The results of a yeast two-hybrid assay indicated that both CEBiP click here and OsCERK1 have the potential to form hetero- or homo-oligomers. Immunoprecipitation using a membrane preparation from rice

cells treated with chitin oligosaccharides suggested the ligand-induced XMU-MP-1 manufacturer formation of a receptor complex containing both CEBiP and OsCERK1. Blue native PAGE and chemical cross-linking experiments also suggested that a major portion of CEBiP exists as homo-oligomers even in the absence of chitin oligosaccharides.”
“Anthrax lethal

toxin (LT) and edema toxin (ET) are the major virulence factors of anthrax and can replicate the lethality and symptoms associated with the disease. This review provides an overview of our current understanding of anthrax toxin effects in animal models and the cytotoxicity (necrosis and apoptosis) induced by LT in different cells. A brief reexamination of early historic findings on toxin in vivo effects in the context of our current knowledge is also presented. Published by Elsevier Ltd.”
“Hepatitis C virus (HCV) infection is frequently associated with hepatic steatosis,

particularly in patients with HCV genotype-3 (HCVGT3). It has variously been hypothesized, largely from in-vitro studies, to be the result of increased synthesis, decreased metabolism and export of triglycerides. We measured by real-time PCR the expression of genes involved in lipid metabolism [acetyl-Coenzyme A carboxylase alpha, apolipoprotein B (APOB), diacylglycerol O-acyltransferase 2, fatty acid-binding protein 1, fatty acid synthase, microsomal triglyceride transfer protein (MTTP), peroxisome proliferator-activated receptor alpha (PPARA), peroxisome proliferator-activated receptor gamma (PPARG), protein Selleck Autophagy 抑制剂 kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) and sterol regulatory element-binding transcription factor 1 (SREBF1)] in liver biopsies from patients infected with HCV genotype-1 (HCVGT1), HCVGT3 and Hepatitis B (HBV) using beta-glucuronidase (GUSB) and splicing factor arginine/serine-rich 4 (SFRS4) as housekeeping genes. Patients infected with HCVGT3 were younger than those infected with HCVGT1 (36.3 +/- 2.5 vs 45.6 +/- 1.5, P < 0.05, Mann-Whitney) and were more likely to have steatosis (69.2%vs 11.8%).

Cinnamon EO at a concentration of 0 04% had a bacteriostatic acti

Cinnamon EO at a concentration of 0.04% had a bacteriostatic activity after 2 h of incubation. Although slight alterations were detected in the cell structure, this concentration was considered to be bactericidal, since it led to a significant reduction in cell numbers after 24 h. On the other hand, cinnamon EO at a 1.00% concentration

decreased cell counts by 3 log units after 2 h incubation and no viable cell count was detected after 24 h. Transmission electron microscopy INCB018424 indicated that cells treated with 1.00% cinnamon EO were severely damaged and presented cell membrane disruption and cytoplasmic leakage.”
“AimThe study was conducted to assess the sympathovagal balance in patients with polycystic ovary syndrome (PCOS)

using short-term heart rate variability (HRV) analysis and conventional autonomic function tests (CAFT).

MethodsThirty-one newly diagnosed patients with PCOS and 30 age-matched controls were recruited. Body mass index (BMI), waist:hip ratio (WHR), cardiovascular parameters such as basal heart rate (BHR), systolic BAY 1895344 blood pressure (SBP), diastolic blood pressure (DBP) and rate-pressure product (RPP), and fasting blood glucose (FBG) were measured in both groups. Cardiovascular autonomic functions assessed were spectral analysis of HRV, heart rate and blood pressure response to standing (30:15 ratio), deep breathing (E:I ratio) and isometric handgrip (DBPihg).

ResultsThe cases had significantly increased BMI, WHR, BHR, SBP, DBP and RPP. Ratio of low-frequency to high-frequency power of HRV (LF-HF ratio), the marker of sympathovagal balance was significantly increased in cases compared to controls. Time-domain indices of HRV and E:I ratio were decreased, and 30:15 ratio, DBPihg and FBG were increased in cases. Though there was a significant correlation of LF-HF ratio with BMI, WHR, BHR, RPP and FBG, only BHR and RPP had independent contribution to LF-HF ratio.

ConclusionWe conclude that PCOS

patients have altered MK-4827 concentration autonomic modulation in the form of increased sympathetic and decreased parasympathetic reactivity and HRV. The sympathovagal imbalance exposes them to cardiovascular morbidities.”
“Genetic testing for BRCA1/2 has psychosocial impacts including those related to views of personal health, sense of self and identity and body image. The centrality of a person’s self-concept in maintaining physical and psychosocial well-being has been well recognized; however, to date research exploring altered self-concept related to carrier knowledge is limited.

Objective: The objective of the study was to develop and validate a scale to measure the self-concept among individuals testing positive for BRCA1/2 mutations.

Methods: The study was conducted in two phases: phase 1: item generation and refinement and phase II: scale selection and initial validation.

001) No ethnic differences in ICAM-1 were observed Conclusion

001). No ethnic differences in ICAM-1 were observed. Conclusion. These results suggest that SA are more susceptible to the detrimental effects of hyperglycaemia-induced oxidative stress at lower blood glucose thresholds than WE. Further research into the potential mechanisms involved is warranted.”
“A fluorine-doped tin oxide AZD0530 (FTO)/zinc sulfide (ZnS)/[6,6]-phenyl C(61) butyric acid methyl ester (PCBM) : regioregular poly(3-hexylthiophene) (P3HT)/poly(3,4-ethylenedioxylenethiophene): poly(4-styrene sulfonic acid) (PEDOT:PSS)/Au type organic solar cell (FTO/ZnS/PCBM:P3HT/PEDOT: PSS/Au, ZnS cell) with a 1

cm(2) active area was first developed using transparent ZnS prepared on a FTO electrode by a chemical bath deposition method. The ZnS inserted solar cells were investigated by photocurrent-voltage (I-V) and ac impedance spectroscopy (IS) measurements. In photo I-V measurements, the ZnS cell exhibited scattered power conversion efficiencies (eta) of 0.7%-1.2% when

the FTO/ZnS electrode was not immersed in various aqueous solutions before the fabrication of the ZnS cells. In contrast, the solar cells with a surface-modified FTO/ZnS electrode by immersing in 0.1M Na(2)S solutions at pH 7-9 containing hydrosulfide ions (HS(-)) exhibited reproducible eta of 1.5%-1.7%. The electric resistance components in the cell consisting of five layers were separately estimated by the IS measurement. The larger eta of the solar cell using HS-modified ZnS was explained by the fact that the charge transport resistance at the ZnS/PCBM: P3HT interface became Sotrastaurin smaller due to this surface modification. When a continuous light irradiation was carried selleck kinase inhibitor out for the modified cells, the resistance at the ZnS/PCBM: P3HT interface increased, being accompanied by the decrease in the eta. That is, the cell performance was controlled

mainly by charge transport velocity at the ZnS/PCBM: P3HT interface. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3153970]“
“Soil has been regarded as a rich source of antibiotic resistance genes (ARGs) due to the complex microbial community and diverse antibiotic-producing microbes in soil, however, little is known about the ARGs in unculturable bacteria. To investigate the diversity and distribution of ARGs in soil and assess the impact of agricultural practice on the ARGs, we screened soil metagenomic library constructed using DNA from four different agricultural soil for ARGs. We identified 45 clones conferring resistance to minocycline, tetracycline, streptomycin, gentamicin, kanamycin, amikacin, chloramphenicol and rifampicin. The similarity of identified ARGs with the closest protein in GenBank ranged from 26% to 92%, with more than 60% of identified ARGs had low similarity less than 60% at amino acid level.

The primary end point was overall survival Secondary end points

The primary end point was overall survival. Secondary end points included quality of life, time to castration-resistant disease, and duration of nontreatment intervals.


Of 1386 enrolled patients, 690 were randomly assigned to intermittent therapy and 696 to continuous therapy. Median follow-up was 6.9 years. There were no significant between-group differences in adverse events. In the intermittent-therapy group, full testosterone

recovery occurred in 35% of patients, and testosterone recovery to the trial-entry Rabusertib mouse threshold occurred in 79%. Intermittent therapy provided potential benefits with respect to physical function, fatigue, urinary problems, hot flashes, libido, and erectile function. There were 268 deaths in the intermittent-therapy group and 256 in the continuous-therapy group. Median overall survival was 8.8 years in the intermittent-therapy group versus 9.1 years in the continuous-therapy group (hazard ratio for death, 1.02; 95% confidence interval, 0.86 to 1.21). The estimated 7-year cumulative rates of disease-related death were 18% and 15% in the two groups, respectively (P = 0.24).


Intermittent androgen deprivation was noninferior to continuous therapy with respect to overall survival.

Some quality-of-life factors improved with intermittent therapy. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials. gov number, NCT00003653.)”
“Extracellular signal-regulated protein kinase (ERK1/2) is a member of the mitogen-activated protein kinase (MAPK) signaling pathway and a key molecular target for ethanol (EtOH) and other drugs of abuse.

The aim of the study was to assess the role of two MAPK pathways, ERK1/2 and c-Jun N-terminal kinase (JNK), on the modulation of EtOH and sucrose self-administration.

C57BL/6J mice were trained to lever press on a fixed-ratio 4 schedule with 9% EtOH/2% sucrose, or 2% sucrose, as the reinforcer. In experiments 1 and 2, mice were injected with the MEK1/2 inhibitor SL 327 (0-100 mg/kg) and the JNK inhibitor AS 6012452 EGFR inhibitor (0-56 mg/kg) prior to self-administration.

In experiment 3, SL 327 (0-100 mg/kg) was administered prior to performance on a progressive ratio (PR) schedule of EtOH reinforcement. In experiment 4, SL 327 and AS 601245 were injected 2 h before a locomotor test.

SL 327 (30 mg/kg) significantly increased EtOH self-administration without affecting locomotion. Higher doses of SL 327 and AS 601245 reduced EtOH-reinforced responding and locomotor activity. Reductions of both ligands on sucrose self-administration were due to decreases in motor activity. SL 327 pretreatment had no effect on PR responding.

ERK1/2 activity is more directly involved in modulating the reinforcing properties of EtOH than JNK activity due to its selective potentiation of EtOH-reinforced responding.