These results provide the first direct demonstration of a double dissociation between LEC and MEC inputs to the hippocampus under conditions of exploration typically used to study hippocampal place cells.”
“In this study, we evaluated a new method for registering three-dimensional ultrasound (3DUS) data to external coordinate systems. First, 3DUS was registered to the stereo endoscope of a da Vinci Surgical System by placing a registration tool against an air-tissue boundary so that the 3DUS could image

ultrasound fiducials while the stereo endoscope could image camera markers on the same tool. The common points were buy LY333531 used to solve the registration between the 3DUS and camera coordinate systems. The target registration error (TRE) when imaging through a polyvinyl chloride ( PVC) tissue phantom ranged from 3.85 +/- 1.76 mm to 1.82 +/- 1.03 mm using one to four registration tool positions. TRE when imaging through an ex vivo liver tissue sample ranged from 2.36 +/- 1.01 mm to 1.51 +/- 0.70 mm using one to four registration tool positions. Second, using a similar method, 3DUS was registered to the kinematic coordinate system of a da Vinci Surgical System by using the da Vinci surgical manipulators to identify common points on an air-tissue boundary. TRE when imaging through a PVC tissue phantom ISRIB was 0.95 +/- 0.38 mm. This registration method is simpler and potentially

more accurate than methods using commercial motion tracking systems. This method may be useful in the future in augmented reality systems for laparoscopic

and robotic-assisted surgery.”
“Pressure applied during harvesting of the saphenous vein (SV) graft in coronary artery bypass surgery might change its mechanical properties and thereby decrease the patency. This study was performed to assess the mechanical properties of the SV graft distended manually with different levels of pressure and to determine the pressure level that induces changes in its structure and mechanics. Saphenous vein graft segments, collected from 36 patients undergoing coronary artery bypass surgery, were distended with pressures of either 50-60, 75-100, or 130-150 mmHg. Grafts were tested for the stress-strain relationship; the Young’s moduli at the low- and high-strain regions Tucidinostat nmr were calculated, and their structures were examined by light and electron microscopy. Pressures of 50-60 mmHg did not influence the mechanics of the vein graft, whereas pressures of 75-100 mmHg elevated the elastic modulus of the vein at the low-strain region while pressures above 130 mmHg increased the elastic moduli at both low- and high-strain regions. There was a prominent loss of microfibrils at all distending pressure levels. The mechanical results suggest that distending pressures above 75 mmHg might play a role in graft failure.

Study was conducted to establish the effect of biomimetic formation of apatite layers on polymeric fibers on their mechanical properties. The tensile tests were performed to determine the influence of polymer crystallinity

and the presence of hydroxyapatite nanoparticles (nanoHAp) on mechanical properties of PLGA fibers coated with hydroxyapatite (HAp) layer. HAp deposits on the surfaces of the fibers precipitated from simulated body fluid (SBF). Three types of fibers coated with HAp layers were compared in mechanical tests. The results indicated that by using a biomimetic fiber coating method the mechanical properties of the fibers are affected by their crystallinity. The nanoHAp modified polymer fibers after incubation in SBF were found to have a continuous HAp layer. The layer affected

the mechanical behavior (force-strain function) of the fibers from nonlinear to linear, typical of ceramic materials. The tensile Go6983 price modulus of the fibers with a continuous layer was found to increase with the apatite layer thickness, whereas the tensile strength decreases. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 3702-3709, 2011″
“Models of habitat buy MK5108 preference are widely used to quantify animal-habitat relationships, to describe and predict differential space use by animals, and to identify habitat that is important to an animal (i.e. that is assumed to influence fitness). Quantifying habitat preference involves the statistical comparison of samples of habitat use and availability. Preference is therefore contingent upon both of these samples. The inferences that can be made from use versus availability designs are influenced by subjectivity in defining what is available to the animal, the problem

of quantifying the accessibility of available resources and the framework in which preference is modelled. Here, we describe these issues, document the conditional nature of preference and establish the limits of inferences that can be drawn from these analyses. We argue that preference is not interpretable as reflecting the intrinsic behavioural motivations of the animal, that estimates of preference are not directly comparable among different samples of availability and Wortmannin order that preference is not necessarily correlated with the value of habitat to the animal. We also suggest that preference is context-dependent and that functional responses in preference resulting from changing availability are expected. We conclude by describing advances in analytical methods that begin to resolve these issues.”
“We have solved, in space and time, the effective-mass nonlinear Schrodinger equation for two electron gases in a semiconductor structure. Considering a Coulomb interaction between the electron densities of each sub-band, we have obtained two time-varying moments in the heterostructure with two different frequencies.

sSMC corresponded to the 15q11.2 region (patients 1 and 2), the centromeric chromosome 15 region (patient 3) and the 21p11.2 region (patient 4). Array CGH showed BYL719 mw 3.6-Mb gain for patients 1 and 2 and 0.266-Mb gain for patient 4. Sperm fluorescent in-situ hybridization analyses found ratios of 0.37 and 0.30 of sperm nuclei with sSMC(15) for patients 1 and 2, respectively (P < 0.001). An increase of sperm nuclei with disomy X, Y and 18 was noted for patient 1 compared with control and patient 2 (P < 0.001). Among the genes mapped in

the unbalanced chromosomal regions, POTE B and BAGE are related to the testis and ovary, respectively. The implication of sSMC in infertility could be due to duplication, but also to mechanical effects perturbing meiosis. (C) 2011, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.”
“In the present work, a gastroretentive in situ gelling liquid formulation

for controlled delivery of ranitidine was formulated using sodium alginate (low, medium and high viscosity grades), calcium carbonate (source of cations) and ranitidine. Prepared formulations were evaluated for viscosity, buoyancy lag time and buoyancy duration, drug content and in vitro drug release. Formulation variables such as concentration of sodium alginate, calcium carbonate and drug significantly affected the formulation viscosity, JAK inhibitor floating behavior and in vitro drug release. Analysis of the release pattern showed that the drug release from in situ gel followed a diffusion mechanism.”
“Meiotic segregation patterns of 278 embryos from 41 preimplantation genetic diagnosis cycles of 34 reciprocal translocation carriers were analysed to investigate whether some characteristics of reciprocal translocation, including terminal breakpoints, acrocentric chromosome or carrier gender, are related to meiotic segregation patterns. RepSox The incidence

of normal/balanced karyotypes in translocations with terminal breakpoints was significantly lower than those without terminal breakpoints (6.5% versus 14.4%, P = 0.005). The incidences of adjacent-1 (21.0% versus 29.6%), adjacent-2 (16.1% versus 11.1%) and 3: 1 (41.9% versus 30.6%) segregation were not statistically significantly different in translocations with terminal breakpoints versus those without. Translocation with acrocentric chromosomes showed a significantly lower rate of 2: 2 segregation (39.2% versus 60.2%, P = 0.001) and a higher rate of 3: 1 segregation (43.1% versus 27.3%, P = 0.005) than those without acrocentric chromosomes. The incidence of 2: 2 segregation was significantly higher in male than in female carriers (58.2% versus 45.0%, P = 0.019). This study suggested that reciprocal translocation involving terminal breakpoints resulted in a lower rate of normal/balanced karyotype in preimplantation embryos.

01). It may be postulated that, in planar embryos, the mitotic spindle might have been affected, e. g. sperm centrosome composition or function, which in turn might have led to the observed cleavage anomaly.

RBM Online (c) 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.”
“P>Photodynamic therapy (PDT) is a modern therapy modality, based upon the application of a photosensitizing agent like aminolevulinic acid, a physiological precursor of porphyrins, onto the tissue followed by illumination with light of the visible wavelength spectrum. During this oxygen-dependent Tyrosine Kinase Inhibitor Library high throughput reaction, reactive oxygen species (ROS) are generated that have immunomodulatory or cytotoxic effects. PDT shows excellent cosmetic results especially for its key indication in dermatology – the treatment of non-melanoma skin cancer. The associated pain and the low tissue penetration are the most frequent limiting factors of PDT. We review

basic principles and recent developments in photosensitizers and light sources. Key oncological and non-oncological indications are presented as well.”
“High-resolution transvaginal ultrasound has facilitated the diagnosis of adenomyosis. This study determined the prevalence of this finding in infertile women and its effect on the outcome of IVF/intracytoplasmic sperm injection (ICSI). This prospective study evaluated 275 consecutive women, commencing IVF/ICSI for the first time. Inclusion criteria were adequate ovarian reserve. Women with fibroids or a previous BAY 11-7082 NF-��B inhibitor myomectomy were excluded. All women were screened for adenomyosis by transvaginal ultrasound on three separate occasions. The control group included 256 women and the adenomyosis group included 19 women. There was no significant difference in the ages of women, FSH, cause of infertility, body mass index, total dose of gonadotrophin used and number of oocytes collected

between the two groups. However, women with adenomyosis had a higher mean antral follicle count (P = 0.006). The clinical pregnancy rate (22.2% versus 47.2%) and ongoing pregnancy rate (11.1% versus 45.9%) were significantly lower in women buy Nutlin-3 with adenomyosis and the miscarriage rate (50.0% versus 2.8%) was significantly higher in women with adenomyosis (all P < 0.001). Ultrasound evidence of adenomyosis is found in a significant number of women presenting with infertility and has a negative impact on the outcome of IVF/ICSI. RBM Online (c) 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.”
“The objective of this prospective randomized study was to assess whether spontaneous triggering of ovulation by detecting LH rise with serial serum testing, results in higher pregnancy rates as compared with administration of human chorionic gonadotrophin (HCG) in patients undergoing intrauterine insemination (IUI) in natural cycles. The trial was registered in clinicaltrials.gov as NCT01414673.

Cytotoxic T-Iymphocyte-associated antigen-4 (CTLA-4) serves as a negative regulator of immunity. Recent trials administering fully-human anti-CTLA-4 monoclonal antibodies to patients with melanoma have demonstrated survival benefits. However, treatment with anti-CTLA-4 antibodies is not without potential toxicities. Autoimmune side-effects, such as diarrhea, bowel inflammation

and dermatitis, were the most commonly reported. To build upon the activity seen Selinexor cell line with anti-CTLA-4 antibodies, both in toxicity and efficacy profiles, there has been significant interest in investigating combinations with vaccination strategies. In recent trials, patients who were vaccinated with autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor, and were then infused with anti-CTLA-4

antibodies, demonstrated clinically-significant antitumor immunity without grade-3 or -4 toxicity in most patients. These data demonstrate how Selleckchem LCL161 manipulation of immune regulation has produced patient benefits, and this area is a rich avenue for future investigation.”
“Background: Overnight stays in farming huts are known to pose a risk of malaria infection. However, studies reporting the risk were conducted in the settings of poor net coverage. This study sought to assess whether an overnight stay in a farming hut is associated with an increased risk of malaria infection if insecticide-treated bed nets (ITNs) VX-770 in vitro are properly used.

Methods: A pair of cross-sectional surveys was carried out in the Lamarm district of Sekong province, Laos, in March (dry season) and August (rainy season) in 2008. Questionnaire-based interviews and blood examinations were conducted with farmers

and their household members from three randomly selected villages in March (127 households, 891 people) and August (128 households, 919 people). Logistic regression analysis, adjusted for potential confounding factors, was used to assess the association between malaria infection status and frequency of overnight stays for the two weeks prior to the study in both the seasons.

Results: In March, 13.7% of participants reported staying overnight in a farming hut at least once in the previous two weeks. The percentage increased to 74.6% in August. Not only adults but also young children stayed overnight as often as adults. The use of an ITN the preceding night was common both in farming huts (66.3% in March, 95.2% in August), and in main residences (85.8% in March, 92.5% in August). Logistic regression analysis showed no statistical association between malaria infection status and frequency of overnight stays in farming huts in either study period.

S. population, this incidence Vistusertib mw rate may be reflective of young, athletic cohorts. An improved understanding of the demographic groups at risk can be used to develop future preventive strategies.”
“Objective: The aim of the present

study was to examine whether an association is present between amniotic fluid (AF) galanin and neonatal birth weight (NBW).

Design: Prospective observational study.

Setting: Fetal maternal unit in a tertiary teaching hospital.

Population: Fifty women of singleton pregnancy who underwent amniocentesis during the second trimester and delivered after the 37th week of gestation.

Methods: Amniocentesis 18th-19th gestational week for genetic indication with the use of a 22G needle under real-time sonographic guidance and measurement of galanin concentration in the AF.

Main outcome measures: Association between concentration of AF galanin and NBW at term.

Results: Galanin was isolated in all samples of AF (median concentration 19.95 pg/mL; range: 19.0-21.7). A strong linear correlation between AF galanin and NBW was detected (tau = 0.928; p<0.001). Non-parametric linear regression analysis revealed that galanin concentration could explain 72.1%

of the variance in the NBW, when controlling for gestational week at birth and mother’s body mass index at delivery.

Conclusions: AF galanin during the second trimester seems to have a strong linear correlation with NBW of term {Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|Selleckchem Anti-infection Compound Library|Selleckchem Antiinfection Compound Library|Selleckchem Anti-infection Compound Library|Selleckchem Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|buy Anti-infection Compound Library|Anti-infection Compound Library ic50|Anti-infection Compound Library price|Anti-infection Compound Library cost|Anti-infection Compound Library solubility dmso|Anti-infection Compound Library purchase|Anti-infection Compound Library manufacturer|Anti-infection Compound Library research buy|Anti-infection Compound Library order|Anti-infection Compound Library mouse|Anti-infection Compound Library chemical structure|Anti-infection Compound Library mw|Anti-infection Compound Library molecular weight|Anti-infection Compound Library datasheet|Anti-infection Compound Library supplier|Anti-infection Compound Library in vitro|Anti-infection Compound Library cell line|Anti-infection Compound Library concentration|Anti-infection Compound Library nmr|Anti-infection Compound Library in vivo|Anti-infection Compound Library clinical trial|Anti-infection Compound Library cell assay|Anti-infection Compound Library screening|Anti-infection Compound Library high throughput|buy Antiinfection Compound Library|Antiinfection Compound Library ic50|Antiinfection Compound Library price|Antiinfection Compound Library cost|Antiinfection Compound Library solubility dmso|Antiinfection Compound Library purchase|Antiinfection Compound Library manufacturer|Antiinfection Compound Library research buy|Antiinfection Compound Library order|Antiinfection Compound Library chemical structure|Antiinfection Compound Library datasheet|Antiinfection Compound Library supplier|Antiinfection Compound Library in vitro|Antiinfection Compound Library cell line|Antiinfection Compound Library concentration|Antiinfection Compound Library clinical trial|Antiinfection Compound Library cell assay|Antiinfection Compound Library screening|Antiinfection Compound Library high throughput|Anti-infection Compound high throughput screening| deliveries in singleton pregnancies, even when controlling for important confounders.”
“Objectives: To assess the prevalence of the 19 neuropsychiatric (NP) syndromes in systemic lupus erythematosus (SLE) patients, as defined by the American College of Rheumatology (ACR) in 1999, and better understand the reasons for interstudy variability of prevalence estimates, by performing a meta-analysis of relevant publications.

Methods: A literature search from April 1999 to May 2008 was performed to identify studies investigating NP syndromes

in patients with definite SLE, applying the 1999 ACR case definitions and having a sample size of at least 30 patients. Excluded were studies that did not relate to all 19 NPSLE syndromes, GW4064 in vitro presented duplicate data, or were irrelevant.

Results: Seventeen of 112 identified studies matched the inclusion criteria, reporting on a total of 5057 SLE patients, including 1439 NPSLE patients, with 2709 NPSLE syndromes. In a subanalysis of the 10 higher quality prospective and elicited studies (2049 patients) using the random-effects model, the prevalence of NP syndromes in SLE patients was estimated to be 56.3% (95% CI 42.5%-74.7%), and the most frequent NP syndromes were headache 28.3% (18.2%-44.1%), mood disorders 20.7% (11.5%-37.4%), cognitive dysfunction 19.7% (10.7%-36%), seizures 9.9% (4.8%-20.5%), and cerebrovascular disease 8.0% (4.5%-14.3%), although significant between-study heterogeneity was present (P < 0.05). Autonomic disorder and Guillain-Barre syndrome carried a prevalence of less than 0.1%.

“
“Background: Invasive candidiasis is a leading cause of morbidity and mortality in critically ill infants. Prompt administration of fluconazole and achievement of the therapeutic target (area under the curve 0 to 24 hours > 400 mg*h/L) improve outcomes in candidemic patients. A loading dose of fluconazole is advised for older patients but has not been evaluated in infants. We sought to determine the pharmacokinetics and safety of a fluconazole loading dose in infants at risk for invasive fungal infection.

Methods: We enrolled 10 hospitalized infants < 60 days old with suspected systemic fungal infection in this open-label study; 9 received a 25-mg/kg

fluconazole loading dose followed by a maintenance dose of

12 mg/kg every 24 hours for 4 additional days. Plasma samples were obtained following the loading and steady-state doses (doses 3-5). We used a 1-compartment PCI32765 model to fit the data to estimate pharmacokinetic indices.

Results: Data from 57 drug concentrations obtained from 8 infants (median postnatal age, 16 days [interquartile range, 13-32] and median gestational age, 37 weeks [35-38]) showed that the median fluconazole SIS3 area under the curve 0 to 24 hours (mg*h/L) in this population was 479 (347-496). Of the 8 infants who received the loading dose, 5 (63%) achieved the therapeutic target on the first day of dosing, and all infants achieved a fluconazole 24-hour trough concentration > 8 mu g/mL. No adverse events were thought to be related to fluconazole

therapy.

Conclusions: A loading dose of fluconazole (25 mg/kg) was safe in this small cohort of young infants and achieved the therapeutic target more rapidly than traditional dosing.”
“The pathogenic yeast Candida dubliniensis is increasingly reported as a cause of systemic fungal infections. We compared the virulence of 9 clinical bloodstream isolates of C. dubliniensis with 3 C. albicans isolates in a murine model of invasive candidiasis. Quantification of organisms ACY-241 manufacturer and inflammatory changes in kidneys of infected animals were evaluated in a blinded, systematic manner. Average 7-day mortality among animals infected with C. dubliniensis was 21.0% (33/157 animals; range for strains: 0-57.1%); and with C. albicans 23.2%, (23/99 animals; range for strains: 6.7-85.0%) (p 0.65). Greater strain variation was noted within species than between the two species. Both species comprised strains of either high or low virulence, and six of the nine C. dubliniensis strains showed negligible virulence. Colony counts determined on samples from liver and kidneys did not differ between species. According to histopathological analysis, C. dubliniensis produced significantly lower levels of hyphae than C. albicans (p <0.001). Candida albicans caused a greater inflammatory response in kidneys (p <0.

“
“Objective: To ensure appropriate allocation of research funds, we need methods for identifying high-priority research needs. We developed and pilot tested a process to identify needs for primary clinical research using a systematic review in gestational diabetes mellitus.

Study Design and Setting: We conducted eight steps: abstract research gaps from a systematic review using the Population, Intervention, Comparison, Outcomes, and Settings (PICOS) framework; solicit feedback from the review authors; translate gaps into researchable questions using the PICOS framework;

solicit feedback from multidisciplinary stakeholders at our institution; establish consensus among multidisciplinary Vorinostat clinical trial external stakeholders on the importance of the research questions using the Delphi method; prioritize outcomes; develop conceptual models to highlight research needs; and evaluate the process.

Results: We identified 19 research questions. During the Delphi method, external stakeholders established consensus for 16 of

these 19 questions (15 with “”high”" and 1 with “”medium”" clinical benefit/importance).

Conclusion: We pilot tested an eight-step process to identify clinically important research needs. Before wider application of this process, it should be tested using systematic reviews of other Pfizer Licensed Compound Library diseases. Further evaluation should include assessment of the usefulness of the research needs generated using this process for primary researchers and funders. (C) 2013 Elsevier Inc. All rights reserved.”
“Green coffee oil (GCO) is a potential natural product for application in health care products. In this study, the properties of GCO from spent coffee grains were evaluated aiming its application in sunscreens. GCO showed an intense synergistic effect in SPF value when it was

associated with the synthetic sunscreen ethylhexylmethoxycinnamate, leading to an increase of 20% in SPF. Additionally, the antioxidant activity, the cytotoxicity and the sun protection factor (SPF) of GCO were determined. The results show no cytotoxic effect for skin and liver cells in vitro, even at high concentrations. The results suggest the use of GCO as a potential natural product for sunscreens formulations to improve the efficiency and protection against LXH254 datasheet skin damage. (C) 2013 Elsevier B.V. All rights reserved.”
“Purpose Endothelial progenitor cells (EPCs) are a promising cell source for vascular tissue engineering approaches in surgery. Diverse biomaterials have been used as matrices for EPC cultivation. In this in vitro study, fibrin in combination with growth factors was examined as an optimized culturing scaffold for EPCs.

Methods EPCs were isolated from peripheral blood by density gradient centrifugation and positive selection using CD34-specific magnetic beads. Cells were seeded on fibrin for 3, 5, and 10 days or on fibronectin for control purposes.

The deep understanding of band-structure formation provides direct scheme for adjusting frequency bands and propagation characteristics of elastic waves in one-dimensional phononic crystals.

It will facilitate the design and optimization of phononic crystals to satisfy specific requirements VS-6063 for wave guiding/filtering and vibration control/isolation applications. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3567911]“
“A new amphiphilic copolymer (copoly(MR-BMA-HEA-MAA), PRBHM) containing multihydroxyl segments was designed and synthesized for application in drug carrier. PRBHM can be dissolved in water to form aggregates directly with a critical aggregate concentration (CAC) of 0.0138 mg mL(-1). The chains of PRBHM can be collapsed into hydrophobic globules when pH decreases from neutral to slightly acid condition (pH = 5.0-7.0) in water. Since the hydrophilic hydroxyl group is independent on pH, PRBHM can keep stable both in neutral and slightly acid aqueous solutions. The hydrophobic small molecules such as 5-(4-(4-vinyl-benzyloxy)phenyl)-4,5-dihydro-1,3-diphenyl-1H-pyrazole (PY) can be loaded into PRBHM aggregates via ultrasonic treatment in water, and can be internalized into BEL-7402 cancer cells. The cytotoxicity

determination also indicates the good biocompatibility of PRBHM in potential application as a drug carrier. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 2843-2850, 2011″
“Background: Despite increased awareness of the adverse check details health effects of low vitamin D status, few studies have evaluated 25-hydroxyvitamin D [25(OH)D] status in young children.

Objectives: We aimed to assess vitamin D status on the basis of 25(OH)D and its relation with parathyroid hormone (PTH) and to identify possible predictors of

25(OH)D status in young children living in a country with minimal vitamin D fortification.

Design: Serum 25(OH)D and PTH concentrations were measured in a cross-sectional sample of children aged 12-22 mo [n = 193 for 25(OH)D, n = 144 for PTH] living in Dunedin, New Zealand (latitude: 45 degrees S). Anthropometric, dietary, and sociodemographic GSK3326595 purchase data were collected.

Results: The majority of children sampled in the summer (94%; 47 of 50) had 25(OH)D >50 nmol/L; however, nearly 80% of children sampled in the winter (43 of 55) had serum concentrations <= 50 nmol/L. In season-adjusted multivariate analysis, breastfeeding and higher levels of education were independently associated with lower 25(OH)D concentrations, whereas male sex and cigarette-smoke exposure were positively associated with 25(OH)D (all P < 0.05). Fractional polynomial regression was used to describe the nonlinear relation between serum PTH and 25(OH)D (P < 0.001). When 25(OH)D concentrations were >60-65 nmol/L, a plateau in PTH was evident.

Despite this controversy, the contribution of this targeted signaling to stimulant self-administration Tanespimycin chemical structure has not been directly assessed. We have thus examined whether pharmacological blockade of alpha 1 receptors in the medial prefrontal cortex and ventral tegmental area alters cocaine self-administration. Rats were trained to lever-press for cocaine (1.0 mg/kg/infusion) under a fixed ratio 1 schedule of reinforcement for 10 days. After training, the rats received a bilateral

microinjection of an alpha 1 noradrenergic antagonist (terazosin: 1.0, 5.0, or 10 mM/side), a D1 dopaminergic antagonist (SCH23390: 12.3 mM/side), or saline into either the medial prefrontal cortex or ventral tegmental area immediately before a cocaine self-administration session. Although SCH23390 significantly increased cocaine self-administration when injected into either brain region, terazosin, at all doses and sites tested, failed to alter this behavior. Thus, PRT062607 chemical structure the maintenance of cocaine self-administration appears to be under the influence of D1 dopaminergic, rather than alpha 1 noradrenergic, signaling at these mesocortical sites. NeuroReport 23:325-330 (C) 2012 Wolters Kluwer Health vertical bar Lippincott

Williams & Wilkins.”
“Rationale The novel antipsychotic aripiprazole in use for treatment of schizophrenia is a partial agonist at dopamine D(2) receptors with actions at a variety of other receptors as well. Cocaine is believed to exert an important part of its rewarding effect Cyclosporin A cell line by increasing extracellular levels of dopamine that subsequently act at dopamine D2 receptors.

Objectives As a partial agonist, aripiprazole may antagonize effects at D(2) receptors and we accordingly tested whether aripiprazole could antagonize self-administration of cocaine. Because D(2)-like receptor agonists are self-administered, a D2 receptor partial agonist like aripiprazole might itself be reinforcing. Thus, we also assessed whether mice would acquire self-administration of aripiprazole.

Materials

and methods A single session, mouse self-administration procedure was used.

Results Oral pretreatment with aripiprazole dose-dependently decreased cocaine self-administration under a fixed ratio 1 schedule at the peak cocaine dose (0.03 mg/kg/infusion), reaching significance at 0.2 and 0.4 mg/kg of aripiprazole. Using 0.4 mg/kg, aripiprazole decreased rates of cocaine self-administration without shifting the peak of the dose-response function. There was no effect of aripiprazole per se, suggesting that its inhibitory action was due to effects on cocaine self-administration rather than non-specific motor effects. Aripiprazole was not found to be self-administered in the tested dose range (0.0003-0.3 mg/kg/infusion). The three highest doses (0.03, 0.1, and 0.