Search

Exposure of skin to UV radiation (UVR) prior to allergen exposure can inhibit inflammatory airways disease in mice by reducing effector CD4+ T cells in both the trachea and the airway draining lymph nodes. This study analysed the immunomodulatory properties of UVR delivered to naïve versusallergen pre-sensitised mice. In a model of inflammatory airways disease, BALB/c mice were sensitised by peritoneal injection of the allergen, ovalbumin (OVA) (20 μg/mouse), in the adjuvant, alum (4 mg/mouse), on days 0 and 14. On day 21, the mice were exposed to aerosolised OVA and 24 h later, proliferative responses by the cells in the airway draining lymph nodes were examined. UVR (8 kJ m−2) was administered 3 days prior to first OVA sensitisation (day −3), or OVA aerosol challenge (day 18). UVR before sensitisation reduced immune responses associated with expression of allergic airways disease; seven days after first OVA sensitisation, regulation of OVA-induced proliferation in vitrobut not in vivoby CD4+CD25+ cells from UV-irradiated mice was detected. UVR administered to pre-sensitised mice regulated allergen responsiveness by cells from the airway draining lymph nodes only with a sensitisation protocol involving allergen and adjuvant at 5% strength of the original dose (1 μg OVA in 0.2 mg alum/mouse). These results suggest that UVR may modulate allergic airways disease by two mechanisms. The first, and more potent, is by reducing effector cells in respiratory tissues and requires UV delivery prior to sensitisation. The second, associated with administration to pre-sensitised mice, is weaker and is detected when the mice are sensitised with lower levels of allergen and adjuvant. [ABSTRACT FROM AUTHOR]

INTRODUCTION: 'Early-onset' studies have shown that symptomatic response often occurs early and that early symptomatic response is predictive for later outcome. Limiting factors of these studies include the restriction on symptomatic outcome, the inclusion of mostly moderately ill patients, and the use of various antipsychotics. METHODS: Response and remission rates were assessed in 528 severely ill patients with schizophrenia at baseline, week 2, 4 and 12 using PANSS, SWN-K, CGI-S, and SOFAS. The clinical measures were combined to one outcome criterion (CombOut). Predicitive validity was analyzed for CombOut using linear regression models. RESULTS: Rate and time to response differed markedly between outcome measures. 32% reached positive symptom response at week 2, 58% at week 4 and 85% at week 12. Non-response at week 4, but not at week 2 was predictive for later non-response. The combined outcome criterion was best predicted by early response in subjective wellbeing (T=?7.88, p<0.001) and social functioning (T=?7.43, p<0.001). DISCUSSION: Rate and time to response might depend on sample characteristics and outcome measure. In severely ill patients early antipsychotic response is possibly delayed from the first 2 to the first 4 weeks. Early response in subjective wellbeing and social functioning are strong predictors for overall outcome, which make them a useful supplementation to the assessment of symptomatic response. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Agitation is a common phenomenon in schizophrenia or acute mania. Because of the inability of patients to give informed consent in such situations, data from consenting studies are limited. METHODS: This observational prospective 5-day study evaluated the effectiveness of olanzapine in a sample of highly agitated patients with aggression. Primary endpoint was mean change of the PANSS-Excited Component (PANSS-EC) score. RESULTS: Mean PANSS-EC score at baseline was 25.5 points, 60.2% were severely agitated and 41.6% severely aggressive. A significant decrease in PANSS-EC total score (?13.3 points) was observed with rapid dose escalation and an average daily dose of 21.2?mg/day of olanzapine. 40 patients (24.1%) required treatment with another antipsychotic and 21 patients (12.7%) were not treated with olanzapine at day 5. At endpoint, 64.2% of patients were in remission of agitation. PANSS-EC reduction was not significantly different in patients with or without concurrent benzodiazepine use. DISCUSSION: Severe agitation with aggression may be well controlled with olanzapine in many cases, possibly by higher initial and overall doses of olanzapine. Controlled studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Summary.  N-alkyl-β-alanine oligomers (β-peptoids) with α-chiral side chains [(R)- or (S)-1-(phenylethyl)amino groups] were synthesized and analyzed by CD spectroscopy. These chiral β-peptoid homomers exhibited chain-length-dependent and solvent-dependent ellipticity, strongly indicating the presence of a secondary structure in solution. The CD behaviour was only slightly temperature-dependent upon heating, as also previously observed for stable α-peptoid helices containing the same type of side chains. Thus, the data presented here comprise the first evidence for a chain length-dependent secondary folding of compounds with this novel peptidomimetic backbone design. In addition, applicability of a novel hyphenated technique, HPLC-SPE-NMR/MS, for analysis of crude SPPS reaction products was demonstrated. [ABSTRACT FROM AUTHOR]

Abstract  This paper presents a device that has been designed for tensile loading at medium impact rates (up to 103 s–1) and for performing either interrupted or failure tests. This machine allows us to apply prescribed pre-straining to the specimen, and then apply subsequent loading histories such as impact fatigue. Two specimen loading systems are considered, which make it possible to carry out tests with various ranges of force and various durations of time. A multi-CCD camera system is triggered by a chosen threshold from the force signal. The system is dedicated to the displacement measurement and gives both qualitative and quantitative information about the stretching mechanism leading to fracture. To illustrate the performance of the device, experimental results concerning impact tensile tests at a strain rate of about 300 s–1 are presented, as well as consecutive impact-fatigue tests on two aluminium alloys. [ABSTRACT FROM AUTHOR]

The rehabilitation experiences of Māori who were still reporting disability 24 months after an injury resulting in hospitalisation were investigated in a qualitative study involving in-depth kanohi ki te kanohi (face-to-face) interviews with 12 participants. Disability after injury impacted many aspects of life beyond the physical impact and included impacts on relationships and employment. Participants expressed feelings of boredom, unfulfillment and frustration with dependence on others. The impacts of injury were ongoing with some lasting beyond completion of rehabilitation. [ABSTRACT FROM AUTHOR]

Some aspects of metal-catalyzed heterogeneous enantioselective reactions are reviewed with specific reference to four different systems where the phenomena that control enantioselection appear to be very different. In the case of glucose electro-oxidation, it is clear that any intrinsic chirality present at the metal surface plays a vital role. With α-keto hydrogenation, achiral surfaces modified by the adsorption of chiral agents become effective enantioselective catalysts and the formation of extended arrays of chiral species appears not to be of importance: instead a 1:1 docking interaction controlled by hydrogen bonding between the adsorbed chiral modifier and the prochiral reactant determines the outcome. Hydrogen bonding also plays a central role in β-ketoester hydrogenation, but here fundamental studies indicate that the formation of ordered arrays involving the reactant and chiral ligand isof importance. Asymmetric CC hydrogenation, though relatively little studied, has the potential for major impact in synthetic organic chemistry both on the laboratory scale and in the manufacture of fine chemicals and pharmaceuticals. The structural attributes that determine whether a given chiral ligand is effective have been identified; the ability to form strong covalent bonds with the metal surface while also resisting hydrogenation and displacement by the strongly adsorbing reactant under reaction conditions is an essential necessary condition. Beyond this, ligand rigidity in the vicinity of the chirality center coupled with resistance to SAM formation is a critically important factor whose absence results in racemic chemistry. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the applicability and validity of a clinical global impressions-aggression (CGI-A) scale in retrospective trials. CGI-A scores were derived from clinical records, BPRS scores were assessed prospectively in 101 patients with first-episode psychosis. CGI-A showed highly significant correlations to the brief psychiatric rating scale (BPRS) excited component (BPRS-EC; r=0.32; p=0.001) and BPRS resistance (r=0.25; p=0.011), to aggression at admission (r=0.70; p<0.001) and to involuntary treatment (r=0.55; p<0.001). The CGI-A retains high construct and face validity in retrospective trials. [ABSTRACT FROM AUTHOR]

The adsorption rates onto a range of platinum single-crystal surfaces of key species involved in the proline-directed heterogeneous enantioselective hydrogenation of isophorone were investigated by electrochemical means. Specifically, the uptakes of the prochiral reactant (isophorone), the chiral hydrogenation product (3,3,5-trimethylcyclohexanone), and the chiral directing agent ((R)- and (S)-proline) were examined. The effects of R,S chiral kink sites on the adsorption of (R,S)-proline were also studied. The reactant adsorbs ∼105times faster than the chiral modifier so that under conditions of competitive adsorption the latter is entirely excluded from the metal surface. Supplementary displacement and reaction rate measurements carried out with practical Pd/carbon catalysts show that under certain reaction conditions isophorone quickly displaces preadsorbed proline from the metal surface. Thus both kinetics and thermodynamics ensure that the chiral modifier can play no role in any surface-mediated process that leads to enantiodifferentiation. These results are fully consistent with the recent proposal1that the crucial step leading to enantiodifferentiation occurs in the solution phase and not at the metal surface. In addition, it is found that there is no preferred diastereomeric interaction between (R,S)-proline and R,S step kink sites on Pt643 and Pt976, implying that such sites do not play a role in determining the catalytic behavior of supported metal nanoparticles. [ABSTRACT FROM AUTHOR]

The dissociative adsorption and decomoposition on a range of metal surfaces of an alkane, an alkene, and an aromatic, all representative of species present in an important technological application, has been studied under conditions relevant to selective gas sensing based on solid electrolyte potentiometry. At 870 K, pure polycrystalline Pt surfaces do not discriminate between n-hexane, toluene, and 1-butene:  graphitic carbon accumulation occurs at almost the same rate. However, by varying the composition of polycrystalline bimetallic Pt/Au surfaces, good discrimination between these species can be achieved. Thus at a nominal surface composition of ∼75% Au (XPS), good selectivity toward 1-butene and toluene uptake is achieved, with essentially no response to n-hexane. At ∼80% Au the system is selective to 1-butene alone. Particular merits of these systems include good high-temperature stability and good tunability of their chemical selectivity. This makes possible the development of array devices in which the elements have overlapping but different selectivity profiles. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increased second-trimester levels of maternal serum HCG in IVF conceptions lead to an increased false-positive rate in Down syndrome screening. Increased levels of cell-free fetal DNA (cffDNA) in maternal plasma have been correlated with increased HCG levels. Our aim was to determine whether cffDNA levels are elevated in IVF pregnancies compared with natural pregnancies. METHODS: Sixteen archived second-trimester serum samples from IVF pregnancies were matched with five control samples from naturally conceived pregnancies per case, all carrying a singleton male fetus. cffDNA concentrations were measured by real-time PCR amplification of a Y chromosome sequence and compared with four standard second trimester serum screening markers (a-fetoprotein, estriol, HCG and inhibin A). RESULTS: Mean cffDNA levels for cases and controls were 57.9 and 57.1 genome equivalents/ml, respectively (P = 0.95). Mean observed rank (from 1 to 6) of cffDNA was 3.625 in the IVF conceived group, compared with an expected value of 3.5 (P = 0.53). No significant correlations were observed between cffDNA and serum markers. CONCLUSIONS: IVF does not affect levels of cffDNA, which appears to be independent of traditional screening markers (e.g. HCG). Therefore, cffDNA can be used as an additional serum marker (e.g. Down syndrome screening) without adjustment for IVF pregnancies. [ABSTRACT FROM AUTHOR]

Large gold particles catalyze alkene epoxidation by NO2 under mild conditions, oxygen adatoms being the likely active species. [ABSTRACT FROM AUTHOR]

A detailed study of ammonia synthesis from hydrogen and nitrogen in a planar dielectric barrier discharge (DBD) reactor was carried out. Electrical parameters were systematically varied, including applied voltage and frequency, electrode gap, and type of ferroelectric material (BaTiO3 versus PZT). For selected operating conditions, power consumption and plasma electron density were estimated from Lissajous diagrams and by application of the Bolsig  +  model, respectively. Optical emission spectroscopy was used to follow the evolution of plasma species () as a function of applied voltage with both types of ferroelectric material. PZT gave both greater energy efficiency and higher ammonia yield than BaTiO3: 0.9 g NH3 kWh−1 and 2.7% single pass N2 conversion, respectively. This performance is substantially superior to previously published findings on DBD synthesis of NH3 from N2 and H2 alone. The influence of electrical working parameters, the beneficial effect of PZT and the importance of controlling reactant residence time are rationalized in a reaction model that takes account of the principal process variables [ABSTRACT FROM AUTHOR]

The parent cage [Ti16O16(OEt)32] readily undergoes ligand exchange with a range of primary alcohols to yield species of the type [Ti16O16(OEt)32−x(OR′)x], with R′ = Me, n-Pr, and n-Bu with xof up to 8. Attempted ligand exchange using the thiol [HO(CH2)4SH] in an attempt to produce functionalized cages suitable for tethering to Au surfaces failed, resulting only in the polymerization of the Ti oxo-cores. However, the use of the thioether [HO(CH2)4SCH3] resulted in successful thio-functionalization and preservation of the Ti16cage core, likely due to methyl protection on the sulfide which precludes further intermolecular reaction with other cage molecules. ESI-MS and NMR showed that the resulting substituted cage [Ti16O16(OEt)24{O(CH2)4SCH3}8] contained eight methylthio-n-butoxy ligands in two groups of four pseudoequivalent positions. High resolution XPS and STM demonstrated that this sulfide-functionalized cage underwent covalent tethering to Au surfaces involving five sulfur linkages per cage, forming a monolayer of adsorbed species in which the molecular integrity had been preserved. In contrast, the parent oxo-alkoxy cage underwent extensive decomposition, rendering it useless as a building block for specific surface architectures. [ABSTRACT FROM AUTHOR]

The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have been described so far. Here, we describe the synthesis of N-substituted maleimides and their pharmacological evaluation on the recombinant human fatty acid amide hydrolase (FAAH) and on the purified human MGL. A few N-arylmaleimides were previously described (Saario, S. M.; Salo, O. M.; Nevalainen, T.; Poso, A.; Laitinen, J. T.; Jarvinen, T.; Niemi, R.Characterization of the Sulfhydryl-Sensitive Site in the Enzyme Responsible for Hydrolysis of 2-Arachidonoylglycerol in Rat Cerebellar Membranes. Chem. Biol.2005, 12, 649−656) as MGL inhibitors, and along these lines, we present a new set of maleimide derivatives that showed low micromolar IC50and high selectivity toward MGL vs FAAH. Then, structure−activity relationships have been investigated and, for instance, 1-biphenyl-4-ylmethylmaleimide inhibits MGL with an IC50value of 790 nM. Furthermore, rapid dilution experiments reveal that these compounds act as irreversible inhibitors. In conclusion, N-substituted maleimides constitute a promising class of potent and selective MGL inhibitors. [ABSTRACT FROM AUTHOR]

Monoglyceride lipase (MGL) inhibition may offer an approach in treating diseases in which higher 2-arachidonoyglycerol activity would be beneficial. We report here the synthesis and pharmacological evaluation of bis(dialkylaminethiocarbonyl)disulfide derivatives as irreversible MGL inhibitors. Inhibition occurs through interactions with MGL C208 and C242 residues, and these derivatives exhibit high inhibition selectivity over fatty acid amide hydrolase, another endocannabinoid-hydrolyzing enzyme. [ABSTRACT FROM AUTHOR]

A library of 30 β-lactams has been prepared from (3R,4R)-3-[(R)-1′-(tbutyldimethylsilyloxy)-ethyl]-4-acetoxy-2-azetidinone, and the corresponding deacetoxy derivative, by sequential N- and O-functionalizations with various ω-alkenoyl and ω-arylalkanoyl chains. All compounds were selective inhibitors of hFAAH versus hMGL, and IC50values in the nanomolar range (5−14 nM) were recorded for the best representatives. From time-dependent preincubation and rapid dilution studies, and from docking analyses in a homology model of the target enzyme, a reversible mechanism of inhibition of hFAAH is proposed. [ABSTRACT FROM AUTHOR]

Sonogashira coupling of phenylacetylene with iodobenzene has been studied in the presence of metallic Rh nanoparticle catalysts and found to occur viaa surface-mediated heterogeneous route. Homogeneous catalytic processes due to Rh species that may leach into solution were barely detectable within the sensitivity of our experiments. Moreover, larger (8 nm) nanoparticles were found to be much better catalysts than very small ones (2 nm), which is consistent with the hypothesis that steric limitations adversely affect the efficiency of the latter. [ABSTRACT FROM AUTHOR]

Fatty acid amide hydrolyase (FAAH) is one of the main enzymes responsible for terminating the signaling of endocannabinoids in the brain. Imaging FAAH in vivo using PET or SPECT is important to deeper understanding of its role in neuropsychiatric disorders. However, at present, no radioligand is available for mapping the enzyme in vivo. Here, we synthesized 18 aryl analogues of anandamide, FAAH’s endogenous substrate, and in vitro evaluated their potential as metabolic trapping tracers. Interaction studies with recombinant FAAH revealed good to very good interaction of the methoxy substituted aryl anandamide analogues 17, 18, 19, and 20with FAAH and they were identified as competing substrates. Compounds 17and 18did not display significant binding to CB1and CB2cannabinoid receptors and stand out as potential candidate metabolic trapping tracers. They were successfully labeled with 11C in good yields and high radiochemical purity and displayed brain uptake in C57BL/6J mice. Radioligands [11C]-17and [11C]-18merit further investigation in vivo. [ABSTRACT FROM AUTHOR]

CB2receptor selective ligands are becoming increasingly attractive drugs due to the potential role of this receptor in several physiopathological processes. Thus, the development of our previously described series of 4-oxo-1,4-dihydroquinoline-3-carboxamides was pursued with the aim to further characterize the structure−affinity and structure−functionality relationships of these derivatives. The influence of the side chain was investigated by synthesizing compounds bearing various carboxamido and keto substituents. On the other hand, the role of the quinoline central scaffold was studied by synthesizing several 6-, 7-, or 8-chloro-4-oxo-1,4-dihydroquinolines, as well as 4-oxo-1,4-dihydronaphthyridine and 4-oxo-1,4-dihydrocinnoline derivatives. The effect of these modifications on the affinity and functionality at the CB2receptor was studied and allowed for the characterization of new selective CB2receptor ligands. [ABSTRACT FROM AUTHOR]

Despite a significant body of literature on the photocatalytic decomposition of 4-chlorophenol by TiO2at liquid/solid and gas/solid interfaces, a fundamental understanding of the interaction of 4-chlorophenol with TiO2is lacking. We present the first study of this interaction under well-defined UHV conditions by means of NEXAFS, time-dependent XPS, and UPS. XPS data show that the molecule adsorbs with the carbon framework intact and no scission of the C−Cl bond. The NEXAFS results indicate a coverage-dependent tilted geometry for the adsorbed molecule that is attached to the surface via a phenolate link. In contrast, because of the absence of an OH functionality, 1,2,4-trichlorobenzene lies flat. The adsorption of 4-chlorophenol is accompanied by a decrease in the TiO2work function pointing to adsorbate → substrate charge transfer. Interestingly, the UPS data suggest that 4-chlorophenol adsorption leads to the photosensitization of TiO2, thus providing a basis for understanding recent results on the visible light photocatalytic activity of TiO2for 4-chlorophenol decomposition. It is also found that the molecule is stable against thermaldecomposition at temperatures of up to ∼473 K, which is well above the temperature range used for photocatalytic decomposition studies. [ABSTRACT FROM AUTHOR]

Background Treatment of proximal humerus fractures in elderly patients is challenging because of reduced bone quality. We determined the in vitro characteristics of a new implant developed to target the remaining bone stock, and compared it with an implant in clinical use. Methods Following osteotomy, left and right humeral pairs from cadavers were treated with either the Button-Fix or the Humerusblock fixation system. Implant stiffness was determined for three clinically relevant cases of load: axial compression, torsion, and varus bending. In addition, a cyclic varus-bending test was performed. Results We found higher stiffness values for the humeri treated with the ButtonFix system - with almost a doubling of the compression, torsion, and bending stiffness values. Under dynamic loading, the ButtonFix system had superior stiffness and less K-wire migration compared to the Humerusblock system. Interpretation When compared to the Humerusblock design, the ButtonFix system showed superior biomechanical properties, both static and dynamic. It offers a minimally invasive alternative for the treatment of proximal humerus fractures. [ABSTRACT FROM AUTHOR]

We examined the impact of the distribution of information regarding social groups on the formation of shared stereotypes within triads in two studies. Three-person groups discussed which of three groups (A, B, and C) was the most able and the most sociable. In Study 1, some of the information about these three groups was available to all group members (shared) whereas the remainder was distributed among group members (unique). Based on the total profile, there was more evidence of group A being sociable and of group B being able than of A being able and B sociable. In Study 1 (n = 58), sampling was manipulated as ‘representative’ (information in line with the overall differences was shared) or ‘unrepresentative’ (only information contradicting these differences was shared). In a third condition, all items of information were shared. Emerging stereotypes were directly influenced by sampling of information independently of the discussion. As well as this, the discussion consensualized initial stereotypes. In Study 2 (n = 52), sampling was always unrepresentative and we manipulated the labels associated with the target groups in such a way that the stereotype associated with the label was either inconsistent or consistent with the overall differences between the target groups. In the inconsistent condition, participants were more likely to discuss information that violated stereotypical expectations, and to be less influenced by sampling as a result of discussion. Altogether, these findings suggest that information sampling directly affects the consensualization of social stereotypes. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]