bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence ofMoringa oleiferaon pharmacokinetic disposition of rifampicin using HPLC‐PDA method: a pre‐clinical study
Authors: Pal Anirban , Bawankule Dnyaneshwar Umrao , Darokar Mahendra Pandurang , Gupta Subhash Chandra , Arya Jai Shankar , Shanker Karuna , Gupta Madan Mohan , Yadav Narayan Prasad , Singh Khanuja Suman Preet
Published: September 2010

The influence of active fraction isolated from pods of an indigenous plant,Moringa oleifera(MoAF) was studied on the pharmacokinetic profile of the orally administered frontline anti‐tuberculosis drug rifampicin (20 mg/kg b.w.) in Swiss albino mice. The antibiotic rifampicin alone and in combination withMoAF(0.1 mg/kg b.w.) was administered orally and heparanized blood samples were collected from the orbital plexus of mice for plasma separation at 0, 1, 2, 3, 4 and 5 h, post treatment. Plasma rifampicin concentration, pharmacokinetic parameters and drug metabolizing enzyme (cytochrome P‐450) activity were determined. The pharmacokinetic data revealed thatMoAF‐treated animals had significantly increased rifampicin plasma concentration,Cmax,Kel,t½(a),t½(el),Kaand AUC as well as inhibited rifampicin‐induced cytochrome P‐450 activity. In conclusion, the result of this study suggested that the bioavailability‐enhancing property ofMoAFmay help to lower the dosage level and shorten the treatment course of rifampicin. Copyright © 2010 John Wiley & Sons, Ltd.
Identification of chemical constituents in Rhizoma Paridis Saponins and their oral administration in rat plasma by UPLC/Q‐TOF/MS
Authors: Man Shuli , Gao Wenyuan , Zhang Yanjun , Huang Luqi , Liu Changxiao
Published: September 2010

On‐line ultra‐performance liquid chromatography (UPLC) coupled with diode‐array detection (UPLC/DAD) and electrospray ionization quadrupole time‐of‐flight mass spectrometry (ESI‐Q‐TOF‐MS) were used for separation, identification and structural analyses of saponins in Rhizoma Paridis saponins (RPS) and rat plasma after oral administration of RPS. Thirty steroidal saponins in RPS were identified by comparing their retention time, accurate mass measurement and positive and negative mass spectrometry data with that of reference compounds. The UPLC/Q‐TOF‐MS method was proved to be rapid and efficient in that 30 steroidal saponins, including three kinds of saponins (prototype, pennogenyl and diosgenyl saponins) were tentatively characterized within 6 min. After oral administration of RPS, 21 original saponins were absorbed in RPS‐treated rat plasma. Our results indicated that UPLC/Q‐TOF‐MS is a rapid and effective tool for identification of a series of saponins at trace level. Copyright © 2010 John Wiley & Sons, Ltd.
Simultaneous determination of three acidic herbicide residues in food crops using HPLC and confirmation via LC‐MS/MS
Authors: Shin Eun‐Ho , Choi Jeong‐Heui , Abd El‐Aty A. M. , Khay Sathya , Kim Sun‐Ju , Im Moo Hyeog , Kwon Chan‐Hyeok , Shim Jae‐Han
Published: September 2010

2,4‐D, dicamba and 4‐CPA with auxin‐like activity have been intensively used in agriculture, for the control of unwanted broadleaf weeds. An analytical method involving HPLC coupled with UVD was developed for the simultaneous analysis of these three analytes in Chinese cabbage, apple and pepper fruits (representative non‐fatty samples) and brown rice and soybean (representative fatty samples) using liquid‐liquid partitioning and column cleanup procedures. The residues were confirmed via tandem mass spectrometry (MS/MS) in ion electrospray ionization (ESI) mode. The standard curves were linear over the range of the tested concentrations (0.25–10 µg/mL), as shown by a marked linearity in excess of 0.9999 (r2). The average recoveries (mean, n = 3) ranged from 94.30 to 102.63 in Chinese cabbage, from 94.76 to 108.47 in apple, from 97.52 to 102.27 in pepper, from 76.19 to 101.90 in brown rice, and from 74.60 to 107.39 in soybean. The relative standard deviations (RSDs) were <9% in all tested matrices. The limits of detection and quantitation were 0.006 and 0.02 mg/kg, respectively. Samples purchased from local markets were analyzed to evaluate the applicability of the methods developed herein. The concentration of the 2,4‐D residue was measured at 0.102 mg/kg in the soybean sample; however, this level is exactly the same MRL set by the Korea Food and Drug Administration. This developed method deserves full and complete consideration, as it clearly displays the sensitivity, accuracy and precision required for residue analysis of 2,4‐D, dicamba and 4‐CPA in food crops. Copyright © 2010 John Wiley & Sons, Ltd.
Cycloaddition des Méthylazide et Phénylazide au β‐Nitrostyrène et au Nitropropène Homologue
Authors: Cailleux P. , Piet J. C. , Benhaoua H. , Carrié R.
Published: September 2010

Phenylazide and methylazide reacts with title olefines and gives two isomeric triazoles without nitro group, and 4‐nitro‐1,2,3 triazole. The isomerisation of starting alkenes explains the formation of isomeric triazoles. Oxydation of amino‐nitro‐diazocompounds in equilibrium with 1,2,3 triazolines leads to 4‐nitro‐1,2,3 triazoles.
Variation of the number of metal atoms involved in active sites and of the true activation energy of hydrocarbon conversion and co hydrogenation over metals
Authors: Martin Guy Antonin
Published: September 2010

According to the model of ensemble, most of the kinetic features of a catalytic reaction can be described by a simple equation involving only two adjustable parameters, the true activation energy, Eo, and the nuclearity, X, of the active site which consists of an ensemble composed of X adjacent free metal atoms. This review paper shows that for one given reaction, X does not change from one metal to another (CH4‐D2 exchange over Ni and Rh). In contrast, it varies dramatically from one reaction to another, addition reaction being associated with low X values, and reactions involving C‐H and C‐C bond cleavage requiring progressively larger nuclearities.

In contrast, Eo varies little with the type of reaction which is considered. In the same way, q, the energy characteristic of active sites, deduced from the slope of the curve obtained by plotting the apparent activation energy, Ea, versus y, the order with respect to the reactant which is the most abundant on the surface of the catalyst (Temkin's equation) does not depend much on the type of reaction. This yields a unique curve when considering a series of reactions over several metals in a Ea vs y representation. Finally, it is observed that Eo=q for the case of five reactions, for still unclear reasons.
Catalytic automotive exhaust gas depollution: Present status and new trends
Authors: Prigent Michel
Published: September 2010

A review is made of the various types of exhaust gas aftertreatment systems presently used on most vehicles to reduce pollutant emissions. The systems are differentiated by their mode of action, according to the engine type to be depolluted (2‐strokes, 4‐strokes, diesel or spark‐ignition), and by their type of make‐up. The major developments foreseen in the future, in view of compliance with the new legislations, are described. Means enabling some prototype vehicles with internal combustion engines to emit pollutant quantities really close to zero, such as electric cars, are described.
Structural and Functional Analysis of Human Liver‐Expressed Antimicrobial Peptide 2
Authors: Henriques Sónia Troeira , Tan Chia Chia , Craik David J. , Clark Richard J.
Published: September 2010

Human liver‐expressed antimicrobial peptide 2 (LEAP‐2) is a cationic antimicrobial peptide (CAMP) believed to have a protective role against bacterial infection. Little is known about the structure–activity relationships of LEAP‐2 or its mechanism of action. In this study we describe the structure of LEAP‐2, analyze its interaction with model membranes, and relate them to the antimicrobial activity of the peptide. The structure of LEAP‐2, determined by NMR spectroscopy, reveals a compact central core with disorder at the N and C termini. The core comprises a β‐hairpin and a 310‐ helix that are braced by disulfide bonds between Cys17–28 and Cys23–33 and further stabilized by a network of hydrogen bonds. Membrane‐affinity studies show that LEAP‐2 membrane binding is governed by electrostatic attractions, which are sensitive to ionic strength. Truncation studies show that the C‐terminal region of LEAP‐2 is irrelevant for membrane binding, whereas the N‐terminal (hydrophobic domain) and core regions (cationic domain) are essential. Bacterial‐growth‐inhibition assays reveal that the antimicrobial activity of LEAP‐2 correlates with membrane affinity. Interestingly, the native and reduced forms of LEAP‐2 have similar membrane affinity and antimicrobial activities; this suggests that disulfide bonds are not essential for the bactericidal activity. This study reveals that LEAP‐2 has a novel fold for a CAMP and suggests that although LEAP‐2 exhibits antimicrobial activity under low‐salt conditions, there is likely to be another physiological role for the peptide.
Anion–π Interactions in Salts with Polyhalide Anions: Trapping of I42−
Authors: Müller Michael , Albrecht Markus , Gossen Verena , Peters Tanja , Hoffmann Andreas , Raabe Gerhard , Valkonen Arto , Rissanen Kari
Published: September 2010

The directionality of interaction of electron‐deficient π systems with spherical anions (e.g,. halides) can be controlled by secondary effects like NH or CH hydrogen bonding. In this study a series of pentafluorophenyl‐substituted salts with polyhalide anions is investigated. The compounds are obtained by aerobic oxidation of the corresponding halide upon crystallization. Solid‐state structures reveal that in bromide 2, directing NH–anion interactions position the bromide ion in an η1‐type fashion over but not in the center of the aromatic ring. The same directing forces are effective in corresponding tribromide salt 3. In the crystal, the bromide ion is paneled by four electron‐deficient aromatic ring systems. In addition, compounds 4 and 6, which have triiodide and the rare tetraiodide dianion as anions, are described. Computational studies reveal that the latter is highly unstable. In the present case it is stabilized by the crystal lattice, for example, by interaction with electron‐deficient π systems.
ChemInform Abstract: New Phosphorus Derivatives of Nitrosoalkanes and Oximes
Authors: HUND H. , ROESCHENTHALER G.‐V.
Published: September 2010

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A hybrid process for chiral separation of compound‐forming systems
Authors: Gou Linzhu , Robl Simone , Leonhard Kai , Lorenz Heike , Sordo Magdalena , Butka Annamaria , Kesselheim Stefan , Wolff Morris , Seidel‐Morgenstern Andreas , Schaber Karlheinz
Published: September 2010

The resolution of chiral compound‐forming systems using hybrid processes was discussed recently. The concept is of large relevance as these systems form the majority of chiral substances. In this study, a novel hybrid process is presented, which combines pertraction and subsequent preferential crystallization and is applicable for the resolution of such systems. A supported liquid membrane applied in a pertraction process provides enantiomeric enrichment. This membrane contains a solution of a chiral compound acting as a selective carrier for one of the enantiomers. Screening of a large number of liquid membranes and potential carriers using the conductor‐like screening model for realistic solvation method led to the identification of several promising carriers, which were tested experimentally in several pertraction runs aiming to yield enriched (+)‐(S)‐mandelic acid (MA) solutions from racemic feed solutions. The most promising system consisted of tetrahydronaphthalene as liquid membrane and hydroquinine‐4‐methyl‐2‐quinolylether (HMQ) as chiral carrier achieving enantiomeric excesses of 15% in average. The successful production of (+)‐(S)‐MA with a purity above 96% from enriched solutions by subsequent preferential crystallization proved the applicability of the hybrid process. Chirality, 2011. © 2010 Wiley‐Liss, Inc.
Enantioselective σ1receptor binding and biotransformation of the spirocyclic PET tracer 1′‐benzyl‐3‐(3‐fluoropropyl)‐3H‐spiro[[2]benzofuran‐1,4′‐piperidine]
Authors: Wiese Christian , Maestrup Eva Große , Schepmann Dirk , Grimme Stefan , Humpf Hans‐Ulrich , Brust Peter , Wünsch Bernhard
Published: September 2010

It was shown that racemic (±)‐2[1′‐benzyl‐3‐(3‐fluoropropyl)‐3H‐spiro[[2]benzofuran‐1,4′‐piperidine],WMS‐1813] represents a promising positron emission tomography (PET) tracer for the investigation of centrally located σ1receptors. To study the pharmacological activity of the enantiomers of2, a preparative HPLC separation of(R)‐2and(S)‐2was performed. The absolute configuration of the enantiomers was determined by CD‐spectroscopy together with theoretical calculations of the CD‐spectrum of a model compound. In receptor binding studies with the radioligand [3H]‐(+)‐pentazocine,(S)‐2was thrice more potent than its (R)‐configured enantiomer(R)‐2. The metabolic degradation of the more potent (S)‐enantiomer was considerably slower than the metabolism of(R)‐2. The structures of the main metabolites of both enantiomers were elucidated by determination of the exact mass using an Orbitrap‐LC‐MS system. These experiments showed a stereoselective biotransformation of the enantiomers of2. Chirality, 2011. © 2010 Wiley‐Liss, Inc.
Vortex‐induced chiral bifurcation in aggregating insulin
Authors: Dzwolak Wojciech
Published: September 2010

Chiral symmetry breaking occurs during vortex‐assisted crystallization of several simple compounds leading to a stochastically determined emergence of an enantiomeric excess of one chiral isomer. This article summarizes recent developments in studies of a similar phenomenon observed in agitated solutions of aggregating insulin, when a phase transition—precipitation of insoluble amyloid fibrils from solutions of the native protein—is coupled to a conformational transition of the native alpha‐helical structure into aggregated beta‐sheets. In contrast to the previously known cases of chiral bifurcation, the substrate is built of L‐amino acids and, therefore, chirally biased. However, under certain conditions, insulin forms fibrils with superstructural chiral features that are independent of the left‐handedness of amino acid residues, as revealed by the sign of extrinsic Cotton effect induced in amyloid‐bound achiral dye—thioflavin T. The inherent chiral bias of the protein results in a diastereomeric relationship between the two optical isomers of amyloid superstructures and the fact that relative probability of formation of either isomer is temperature dependent. As the formation of amyloid fibrils in vivo is associated with several degenerative disorders such as Alzheimer's disease, this newly observed phenomenon may have important implications in the context of structural basis of biological activity of misfolded proteins. Chirality, 2010. © 2010 Wiley‐Liss, Inc.
Evidence for an hMSH3 defect in familial hamartomatous polyps
Authors: Huang Sherry C. , Lee Jeffrey K. , Smith E. Julieta , Doctolero Ryan T. , Tajima Akihiro , Beck Stayce E. , Weidner Noel , Carethers John M.
Published: September 2010

BACKGROUND:

Patients with hamartomatous polyposis syndromes have increased risk for colorectal cancer (CRC). Although progression of polyps to carcinoma is observed, pathogenic mechanisms remain unknown. The authors examined whether familial hamartomatous polyps harbor defects in DNA mismatch repair (MMR), and assayed for somatic mutation of PTEN, a gene inactivated in the germline of some hamartomatous polyposis syndrome patients.

METHODS:

Ten hamartomatous polyposis syndrome patients were genotyped for germline mutations. Epithelial and nonepithelial polyp DNA were assayed for microsatellite instability (MSI) and PTEN frameshift mutation. DNA MMR and PTEN protein expression were assessed in all polyps by immunohistochemistry. In addition, 99 MSI‐high sporadic CRCs and 50 each of hMLH1−/− and hMSH3−/− cell clones were examined for PTEN frameshifts.

RESULTS:

Twenty‐five (58%) of 43 hamartomatous polyposis syndrome polyps demonstrated dinucleotide or greater MSI in polyp epithelium, consistent with hMSH3 deficiency. MSI domains lost hMSH3 expression, and PTEN expression was lost in polyps from germline PTEN patients; sporadic hamartomatous polyps did not show any of these findings. PTEN analysis revealed wild type exon 7 and 8 sequences suggestive of nonexistent or rare events for PTEN frameshifts; however, MSI‐high sporadic CRC showed 11 (11%) of 99 frameshifts within PTEN, with 4 tumors having complete loss of PTEN expression. Subcloning hMLH1−/− and hMSH3−/− cells revealed somatic PTEN frameshifts in 4% and 12% of clones, respectively.

CONCLUSIONS:

Nondysplastic epithelium from hamartomatous polyposis syndrome polyps harbors hMSH3 defects, which may prime neoplastic transformation. Polyps from PTEN+/− patients lose PTEN expression, but loss is not a universal early feature of all hamartomatous polyposis syndrome. However, PTEN frameshifts can occur in hMSH3‐deficient cells, suggesting that hMSH3 deficiency could drive hamartomatous polyposis syndrome tumorigenesis. Cancer 2011. © 2010 American Cancer Society.
Mucinous ovarian carcinoma: Slippery business
Authors: Soslow Robert A.
Published: September 2010

The belief that ovarian mucinous carcinomas are common, clinically unpredictable and often associated with pseudomyxoma peritonei is outmoded. A study from the Gynecologic Oncology Group, published in this edition, makes the case that high‐stage mucinous tumors involving the ovary frequently represent metastases from extraovarian primary sites, are often misdiagnosed, and behave virulently.
Current event‐free survival after sequential tyrosine kinase inhibitor therapy for chronic myeloid leukemia
Authors: Al‐Kali Aref , Kantarjian Hagop , Shan Jianqin , Bassett Roland , Quintás‐Cardama Alfonso , Borthakur Gautam , Jabbour Elias , Verstovsek Srdan , O'Brien Susan , Cortes Jorge
Published: September 2010

BACKGROUND:

Imatinib is an effective tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML) in chronic phase (CP). Although some patients may fail on therapy with imatinib, effective salvage therapy is available with second‐generation TKIs. Current measurement of efficacy for each therapy is judged by its individual impact on overall survival and event‐free survival (EFS).

METHODS:

In total, 586 patients with CML in CP who received imatinib were included in this analysis in 2 cohorts: imatinib as front‐line therapy (n = 281) or after failure on interferon‐α (IFN‐α) (n = 305). By accounting for successful salvage treatment (ie, regain of complete cytogenetic response), the current EFS (CEFS) rate was calculated to obtain a more accurate impression of the outcome of patients with CML who received treatment with sequential TKIs.

RESULTS:

For patients who received imatinib after failing on IFN‐α, the 7‐year EFS rate was 61%, whereas the CEFS rate was 69%. The 7‐year EFS rate for patients who received imatinib as initial therapy was 81% compared with a 7‐year CEFS rate of 88%.

CONCLUSIONS:

CEFS provided a more accurate representation of the outcome of patients with CML in CP. These patients may frequently be treated successfully with subsequent TKIs after experiencing failure on the first TKI. Cancer 2011. © 2010 American Cancer Society
Partial regularity for weak heat flows into spheres
Authors: Chen Yunmei , Li Jiayu , Lin Fang‐Hua
Published: September 2010

In this paper we show that a weak heat flow of harmonic maps from a compact Riemannian manifold (possibly with boundary) into a sphere, satisfying the monotonicity inequality and the energy inequality, is regular off a closed set of m‐dimensional Hausdorff measure zero.
Toward a better understanding of depression and anxiety. The importance of tryptophan hydroxylase activation blockade: The origin of a unique anxiolytic antidepressant
Authors: Gittos Maurice W.
Published: September 2010

The serotonin (5‐HT) deficiency theory of depression has misled medical science. Inhibitors of 5‐HT reuptake were the basis of the hypothesis and display limited efficacy with a pronounced delay of onset in action coupled with a side‐effect profile that includes increased anxiety. In the present commentary, a recommendation for the reinstatement of the prolongation of the d‐amphetamine stereotypy test is made as a means to generate new molecules capable of blocking stress‐induced tryptophan hydroxylase (TPH) activation and its elevation of 5‐HT, now regarded as the cause of depression The selective TPH activation inhibitor, AGN 2979, is already known to exert powerful, rapid antidepressant and anxiolytic properties in the clinic with a notable lack of the side effects associated with monoamine reuptake inhibition. Drug Dev Res 71:331–334, 2010. © 2010 Wiley‐Liss, Inc.
Loss ofLhx1activity impacts on the localization of primordial germ cells in the mouse
Authors: Tanaka Satomi S. , Yamaguchi Yasuka L. , Steiner Kirsten A. , Nakano Toru , Nishinakamura Ryuichi , Kwan Kin Ming , Behringer Richard R. , Tam Patrick P.L.
Published: September 2010

Mouse embryos lackingLhx1(Lim1) activity display defective gastrulation and are deficient of primordial germ cells (PGCs) (Tsang et al. [2001]International Journal of Developmental Biology45:549–555). To dissect the specific role of Lhx1 in germ cell development, we studied embryos with conditional inactivation ofLhx1activity in epiblast derivatives, which, in contrast to completely null embryos, develop normally through gastrulation before manifesting a head truncation phenotype. Initially, PGCs are localized properly to the definitive endoderm of the posterior gut in the conditional mutant embryos, but they depart from the embryonic gut prematurely. The early exit of PGCs from the gut is accompanied by the failure to maintain a strong expression ofIfitm1in the mesoderm enveloping the gut, which may mediate the repulsive activity that facilitates the retention of PGCs in the hindgut during early organogenesis.Lhx1therefore may influence the localization of PGCs by modulatingIfitm1‐mediated repulsive activity. Developmental Dynamics 239:2851–2859, 2010. © 2010 Wiley‐Liss, Inc.
Water framework directive implementation in Greece: Introducing participation in water governance – the Case of the Evrotas River Basin management plan
Authors: Demetropoulou Leeda , Nikolaidis Nikolaos , Papadoulakis Vasilis , Tsakiris Kostas , Koussouris Theodore , Kalogerakis Nikolaos , Koukaras Kostas , Chatzinikolaou Anastasia , Theodoropoulos Kostas
Published: September 2010

Accepting the positive results that public participation can bring in the implementation of the Water Framework Directive (WFD), this paper seeks to contribute to ongoing discussions on the rather problematic WFD implementation in southern Europe. Within this framework, we first focus on the national level and the analysis of ‘water governance’ and ‘public participation’ within the context of WFD implementation in Greece, and secondly on the examination of the participatory methods introduced locally for the preparation of the Evrotas River Basin management plan. The first section focuses on public participation as an indispensable ingredient of good water governance. The next focuses on the introduction of the WFD as an instance of governance that promotes participatory arrangements. We then present the centralized structure of the Greek state as an impediment to the introduction of public participation in water governance. The fourth section focuses on the Evrotas River Basin and describes the participatory arrangements for the preparation of the management plan. The paper concludes with the verification of the need for participatory processes to respect the context within which they are pursued and with specific alterations to the way public participation has been planned and implemented in Greece. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
Effect of three‐dimensional expansion and cell seeding density on the cartilage‐forming capacity of human articular chondrocytes in type II collagen sponges
Authors: Francioli Silvia E. , Candrian Christian , Martin Katja , Heberer Michael , Martin Ivan , Barbero Andrea
Published: September 2010

Chondrocytes for tissue engineering strategies are typically expanded in monolayer (2D), leading to cell dedifferentiation but allowing to generate large cell numbers for seeding into scaffolds. Direct chondrocyte culture in scaffolds, instead, may support better maintenance of the differentiated phenotype but reduce the extent of proliferation and thus the resulting cell density. This study investigates whether the quality of cartilaginous tissues generated in vitro by human articular chondrocytes (HAC) on type II collagen sponges is enhanced (1) by direct expansion on the scaffolds (3D), as compared with standard 2D, or (2) by increasing cell seeding density, which in turn requires extensive 2D expansion. Three‐dimensional expansion of HAC on the scaffolds, as compared with 2D expansion for the same number of doublings, better maintained the chondrocytic phenotype of the expanded cells (13.7‐fold higher levels of type II collagen mRNA) but did not enhance their accumulation of glycosaminoglycan (GAG) following chondrogenic culture. Instead, increasing the HAC seeding density in the scaffolds (from 25 × 103 to 66 × 103 cells/mm3) significantly improved chondrogenesis (up to 3.3‐fold higher GAG accumulation and up to 9.3‐fold higher type II collagen mRNA), even if seeded cells had to be expanded and dedifferentiated more extensively in 2D to reach the required cell numbers. This study indicates that, under the specific conditions tested, a high‐seeding density of HAC in 3D scaffolds is more critical for the generation of cartilaginous constructs than the stage of cell differentiation reached following expansion. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Awake at 4 a.m.: treatment of insomnia with early morning awakenings among older adults
Authors: Fiorentino Lavinia , Martin Jennifer L.
Published: September 2010

Insomnia is a common problem among older adults. In particular, older adults experience insomnia coupled with early morning awakenings due to an interaction between age‐related changes in circadian rhythm timing coupled with behavior changes that contribute to sustained poor sleep. Cognitive–behavioral therapy for insomnia (CBT‐I), at times coupled with circadian interventions (e.g., timed light exposure), are likely to be most successful in optimizing sleep quality. In delivering CBT‐I to older adults, modifications are sometimes necessary to accommodate for medical problems, lifestyle, social factors, and patient preferences. Addition of circadian interventions can ameliorate the negative effects of inappropriately timed sleep as well. These treatment methods can be highly effective and benefits can be long‐standing. A case example is used to illustrate these points. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 66:1–14, 2010.
AMP‐activated protein kinase: ‘a cup of tea’ against cholesterol‐induced neurotoxicity
Authors: Martínez de Morentin Pablo Blanco , González Carmen R , López Miguel
Published: September 2010

Disturbances in brain cholesterol metabolism have been linked to Alzheimer's disease (AD) pathology. A high‐cholesterol diet increases fibrillar amyloid β peptide (Aβ) deposition, inflammation, and apoptosis that eventually results in neurodegeneration and learning and memory impairments. In the October 2010 issue of The Journal of Pathology, Lu and colleagues provided a novel and interesting mechanism that explains how quercetin, a flavonoid found at high concentrations in green and black teas, may help to protect against cholesterol‐induced neurotoxicity through activation of AMP‐activated protein kinase (AMPK), a metabolic energy gauge. Further work will be necessary to address whether AMPK may be a potential target to combat neurodegenerative diseases. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Invited Commentary for Lu et al. Quercetin activates AMP‐activated protein kinase by reducing PP2C expression protecting old mouse brain against high cholesterol‐induced neurotoxicity, Journal of Pathology, 2010; 222 199–212.
The knowledge, perceptions and practice of pharmacovigilance amongst community pharmacists in Lagos state, south west Nigeria
Authors: Oreagba I. A. , Ogunleye O. J. , Olayemi S. O.
Published: September 2010

Purpose

Community Pharmacists both have an important responsibility in monitoring the ongoing safety of medicines and are widely accessible to do it. This study aims to investigate the knowledge, perceptions and practice of Pharmacovigilance amongst community pharmacists in Lagos State, South West Nigeria

Methods

A cross‐sectional observational survey was used in this study. A multistage random sampling technique was employed in the selection of 420 community pharmacies in Lagos.

Results

About 55% of respondents have ever heard of the word ‘Pharmacovigilance’ out of which less than half (representing only 18% of all respondents) could define the term ‘Pharmacovigilance’. Forty percent of the respondents stated that patients reported ADRs to them at least once a month, and 20% reported to the relevant authorities. However only 3% of respondents actually reported an ADR to the National Pharmacovigilance Centre. The most important reason for poor reporting was lack of knowledge about how to report ADRs (44.6%).

Meanwhile, 90% of respondents believed that the role of the pharmacists in ADR reporting was important. Most community pharmacists were willing to practice pharmacovigilance if they were trained.

Conclusion

Community pharmacists in Lagos had poor knowledge about pharmacovigilance. Reporting rate was also poor. There is an urgent need for educational programs to train pharmacists about pharmacovigilance and ADR reporting. Copyright © 2010 John Wiley & Sons, Ltd.
Der Fehlersucher
Authors: Loos Andreas
Published: September 2010

Wenn zwei Astronomen denselben Sterndurchgang beobachten, dann weichen ihre Messungen stets ein wenig voneinander ab. Doch als erfahrener Astronom riecht der Gesuchte hinter solchen Unterschieden mehr als Zufall. Er hält sie für systematische Fehler, abhängig vom jeweiligen Beobachter und dessen Instrument. Das vermeintliche Phänomen tauft er die “persönliche Differenz.” Jahrelang versucht er, ihm auf die Spur zu kommen. Vergeblich.
Handfeste Emulsionen
Authors: Vilgis Thomas
Published: September 2010

Emulsionen aus Öl und Wasser, wie Mayonnaisen, gehören zum Standardprogramm jeder kreativen Küche. Trotz der Formbeständigkeit der Mayonnaisehäubchen auf den Tellern bleibt die Emulsion eine Flüssigkeit. Kleine Scherkräfte reichen aus, und die Mayonnaise beginnt zu fließen. Für feste, schnittfeste Emulsionen hilft es, die kontinuierliche Phase zu gelieren.
Elastic properties of nanowires
Authors: Röhlig Claus‐Christian , Niebelschütz Merten , Brueckner Klemens , Tonisch Katja , Ambacher Oliver , Cimalla Volker
Published: September 2010

The elastic properties of metallic and semiconducting nanowires were analyzed by different techniques employing static and dynamic loads. The reliability of the methods is verified by analyzing well defined microstructures and a good agreement for the values of the Young's modulus determined by the different methods was achieved. For the investigated materials systems (Au, W, Si, InN), basically no differences in the Young's moduli were observed between microstructures, bulk material, and nanowires with radii of 20–300 nm. Microstructure, morphological undulation, defects, and contaminations, however, can drastically change the apparent Young's moduli of nanowires. Examples are given, where an apparent increasing or decreasing of the Young's modulus with decreasing diameter is caused by such effects. The same effects have also influence on the fracture strength in nanowires. While perfect Au nanowires exhibit fracture strengths exceeding the bulk values up to two orders of magnitude, any anomaly causes earlier failure. In addition, failure mechanisms are observed to be dependent on the microstructure. While single crystalline Au nanowires have shown a pure elastic deformation upon load, polycrystalline nanowires show a remarkable plastic deformation before breaking.
Simultaneous selective detection of organophosphate and phthalate esters using gas chromatography with positive ion chemical ionization tandem mass spectrometry and its application to indoor air and dust
Authors: Bergh Caroline , Torgrip Ralf , Östman Conny
Published: September 2010

A selective and sensitive method for the simultaneous determination of 14 organophosphate and six phthalate esters using gas chromatography (GC) and mass spectrometry (MS) is presented. Both of these compound classes are frequently found in the indoor environment due to their use as bulk additives in numerous polymers, consumer products and building materials. GC/MS utilizing positive ion chemical ionisation (PICI) in selected reaction monitoring (SRM) mode with isobutane as the reagent gas was found to be the best of the tested methods; it proved superior to electron ionisation (EI) in selected ion monitoring (SIM) mode and to PICI using methane as the reagent gas. The method was applied to indoor air samples collected by active air sampling using solid‐phase extraction (SPE) cartridges. Organophosphates and phthalates were simultaneously determined with method detection limits (MDLs) in the range of 0.1–47 ng m−3. For most compounds the MDLs were ≤0.2 ng m−3, but due to the presence of some of these ubiquitous indoor air pollutants in the blanks, significantly higher MDLs were observed for a few compounds. Finally, the method was also applied in the screening of a much more complex sample matrix, indoor dust. Copyright © 2010 John Wiley & Sons, Ltd.
Liquid chromatography/tandem mass spectrometry assay for the absolute quantification of the expected circulating apelin peptides in human plasma
Authors: Mesmin Cédric , Dubois Mathieu , Becher François , Fenaille François , Ezan Eric
Published: September 2010

Apelin peptides are of great interest owing to their involvement in physiological and pathological processes and they have been proposed as novel biomarkers for heart failure. The plasma concentrations of bioactive peptides of 12 (apelin‐12), 13 (apelin‐13) and pyroglutamyl apelin‐13 (apelin‐p13), 17 (apelin‐17) and 36 (apelin‐36) amino acids are reported to range from 20 to 4000 pg/mL in healthy subjects. As standard immunoassays cannot specifically quantify each apelin peptide, we have developed a sensitive and targeted multiplexed liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for each plasma apelin fragment. The approach was based on a cation‐exchange extraction step of apelin forms present in human plasma. Apelin‐12, ‐13, ‐p13, ‐17 and ‐36 were quantified using a triple quadrupole mass spectrometer operating in the multiple reaction monitoring mode. Stable isotope‐labeled internal standards were used for quantification. Following assay validation, apelin peptide stability in plasma was investigated. Ten plasma samples from healthy donors were analyzed both with a standard immunoassay and with our LC/MS/MS method. The immunoassay results for the ten healthy donors showed immunoreactive plasma apelin concentrations ranging from 208 to 466 pg/mL. The lower limits of detection of our LC/MS/MS assay ranged from 10 to 50 pg/mL for apelin‐12, ‐13, ‐p13, ‐17, and ‐36. Surprisingly, none of the five expected circulating forms of apelin was detected. These results question the nature and/or the concentration of circulating apelin peptides as well as the specificity of the immunoassays that have hitherto been used for clinical applications. Copyright © 2010 John Wiley & Sons, Ltd.
Impact assessment in the automotive industry: mandatory market introduction of alternative powertrain technologies
Authors: Walther Grit , Wansart Jörg , Kieckhäfer Karsten , Schnieder Eckehard , Spengler Thomas S.
Published: September 2010

Increasing numbers of regulatory measures are being introduced worldwide to reduce emissions from the transportation sector. In California, whose low emission vehicle regulations have a leading position worldwide, automobile manufacturers must reduce greenhouse gas emissions of their vehicle fleet (GHG regulations) and sell increasing shares of zero emission vehicles (ZEV regulations). Manufacturers have to pay high penalties in case of non‐compliance. A dynamic simulation model examines fundamental automobile manufacturer strategies for compliance. Co‐evolutionary development of powertrain technologies, corresponding infrastructure coverage, vehicle types offered, and customer behavior during the adjustment to regulations, is considered. The model is applied to a case study considering the state of California. Results show that meeting requirements necessitates an early introduction of alternative powertrains in many vehicle segments. Feedback between GHG and ZEV regulations necessitates the development of joint compliance strategies. Recommendations are derived concerning appropriate manufacturer strategies for complying with California's regulations. Copyright © 2010 John Wiley & Sons, Ltd.
Adenomatous Polyposis Coli Is Essential for Both Neuronal Differentiation and Maintenance of Adult Neural Stem Cells in Subventricular Zone and Hippocampus
Authors: Imura Tetsuya , Wang Xiaohong , Noda Tetsuo , Sofroniew Michael V. , Fushiki Shinji
Published: September 2010

The tumor suppressor adenomatous polyposis coli (APC) is a multifunctional protein that not only inhibits the Wnt signaling pathway by promoting the degradation of β-catenin but also controls cell polarity, motility, and division. APC is abundantly expressed in the adult central nervous system, but its role in adult neurogenesis remains unknown. Using conditional deletion (or knockout) of APC (APC-CKO) from glial fibrillary acidic protein (GFAP)-expressing cells including adult neural stem cells (NSCs) in the subventricular zone and hippocampal dentate gyrus, we show that APC expression by these cells is a critical component of adult neurogenesis. Loss of APC function resulted in a marked reduction of GFAP-expressing NSC-derived new neurons, leading to the decreased volume of olfactory granule cell layer. Two distinct mechanisms account for impaired neurogenesis in APC-CKO mice. First, APC was highly expressed in migrating neuroblasts and APC deletion disturbed the differentiation from Mash1-expressing transient amplifying cells to neuroblasts with concomitant accumulation of β-catenin. As a result, migrating neuroblasts decreased, whereas Mash1-expressing dividing cells reciprocally increased in the olfactory bulb of APC-CKO mice. Second, APC deletion promoted an exhaustion of the adult germinal zone. Functional NSCs and their progeny progressively depleted with age. These findings demonstrate that APC expression plays a key role in regulating intracellular β-catenin level and neuronal differentiation of newly generated cells, as well as maintaining NSCs in the adult neurogenic niche.
Mechanisms of deadenylation‐dependent decay
Authors: Chen Chyi‐Ying A. , Shyu Ann‐Bin
Published: September 2010

Degradation of messenger RNAs (mRNAs) plays an essential role in modulation of gene expression and in quality control of mRNA biogenesis. Nearly all major mRNA decay pathways characterized thus far in eukaryotes are initiated by deadenylation, i.e., shortening of the mRNA 3′ poly(A) tail. Deadenylation is often a rate‐limiting step for mRNA degradation and translational silencing, making it an important control point for both processes. In this review, we discuss the fundamental principles that govern mRNA deadenylation in eukaryotes. We use several major mRNA decay pathways in mammalian cells to illustrate mechanisms and regulation of deadenylation‐dependent mRNA decay, including decay directed by adenine/uridine‐rich elements (AREs) in the 3′‐untranslated region (UTR), the rapid decay mediated by destabilizing elements in protein‐coding regions, the surveillance mechanism that detects and degrades nonsense‐containing mRNA [i.e., nonsense‐mediated decay (NMD)], the decay directed by miRNAs, and the default decay pathway for stable messages. Mammalian mRNA deadenylation involves two consecutive phases mediated by the PAN2–PAN3 and the CCR4–CAF1 complexes, respectively. Decapping takes place after deadenylation and may serve as a backup mechanism to trigger mRNA decay if initial deadenylation is compromised. In addition, we discuss how deadenylation impacts the dynamics of RNA processing bodies (P‐bodies), where nontranslatable mRNAs can be degraded or stored. Possible models for mechanisms of various deadenylation‐dependent mRNA decay pathways are also discussed. WIREs RNA 2011 2 167–183 DOI: 10.1002/wrna.40

This article is categorized under:

RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms

RNA Turnover and Surveillance > Regulation of RNA Stability
Koordinationsverbindungen als potentielle Photokatalysatoren
Authors: Hennig Horst , Thomas Philipp , Wagener Roland , Rehorek Detlef , Jurdeczka Kristina
Published: September 2010

3. Zusammenfassung

Nach einer einleitenden Betrachtung über die generelle Bedeutung der Photochemie von Koordinationsverbindungen wird das spezielle Interesse an diesen Verbindungen hinsichtlich ihrer Wirkung als Photokatalysatoren begründet. Auf der Grundlage einer definitorischen Abgrenzung von photokatalytischen und photo‐sensibilisierten Reaktionen sowie katalysierten Photolysen (“photoassisted reactions”) werden einfache Reaktionsbeispiele diskutiert. Ausführlich werden photokatalytische Reaktionen von Koordinationsverbindungen in der homogenen Katalyse, für Bildaufzeichnungsverfahren sowie zur Nutzung von Sonnenenergie erörtert. An verschiedenen Beispielen wird die prinzipielle Funktions‐fähigkeit solcher Systeme, einschließlich ihrer praktischen Nutzung, nachgewiesen.
Räumliche Struktur der Moleküle und chiroptische Eigenschaften — neuere Ergebnisse
Authors: Ripperger Helmut
Published: September 2010

11. Zusammenfassung

Als Ergänzung einer früheren Übersicht in dieser Zeitschrift werden neuere Ergebnisse chiroptischer Untersuchungen (ORD und CD) besprochen. Insbesondere werden die Beziehungen zwischen Raumstruktur und optischer Aktivität für Ketone, Olefine, konjugierte Diene, Aromaten, Dithiocarbamate, N‐Chloramine und gekoppelte Oszillatoren diskutiert. An Beispielen wird gezeigt, wie diese Methoden zur Bestimmung der Konfiguration und Konformation von Naturstoffen und verwandten Verbindungen heran‐gezogen werden können.
Schwingungsspektroskopie im Nahen Infrarot
Authors: Salzer Reiner
Published: September 2010

Vibrational spectra in the near infrared show a high selectivity for CH, NH and OH groups. Environmental influences on chemical or physical properties of these groups are indicated with particular sensitivity.

For quantitative analyses there is a worldwide increase in using computer based NIR instruments. Even nontransparent or highly scattering samples are nondestructively analysed by diffuse reflectance techniques. In most advanced methods the excitation by dye lasers replaces the less effective conventional sources and monochromators. With increasing excitation energy in NIR the vibrational behaviour changes from normal modes to local modes. Local modes play a key role in understanding bond‐selective photochemical processes. The investigation of local modes will contribute both to the search for dissociation coordinates as well as to understanding those processes which direct the reactions by their sequence and their time scale.
A Nomogram for Predicting the Probability of Carcinoma in Patients with Intraductal Papillary‐Mucinous Neoplasm
Authors: Shimizu Yasuhiro , Kanemitsu Yukihide , Sano Tsuyoshi , Senda Yoshiki , Mizuno Nobumasa , Yamao Kenji
Published: September 2010

Background

The objective of the present study was to use clinical and laboratory data to develop a model for predicting the presence of carcinoma in patients with intraductal papillary mucinous neoplasm (IPMN).

Methods

Data were collected on 81 patients with IPMN who underwent a pancreatic resection between 1989 and 2008 at Aichi Cancer Center Hospital. Variables analyzed included age, gender, laboratory findings (serum amylase, carcinoembryonic antigen, and carbohydrate antigen 19‐9 level), pancreatic juice cytology grade, and imaging studies. Factors associated with the presence of carcinoma were evaluated by univariate and multivariate logistic regression analysis.

Results

Among the 81 patients with IPMN, 34 (42%) had malignant tumors (noninvasive carcinoma in 22 and invasive carcinoma in 12), and 47 (58%) had adenoma. On multivariate analysis, existing carcinoma was associated with female gender, main pancreatic duct IPMN, nodule size, and pancreatic juice cytology grade. Based on these variables, a predictive nomogram was developed. The area under the receiver operating characteristic curve (AUC) for the model was 0.903. The sensitivity and specificity of the model were 97.1 and 68.1%, respectively, in the validation study, for which the predictive probability of >10% was used to indicate the presence of carcinoma.

Conclusions

The nomogram has high diagnostic predictability for carcinoma in patients with IPMN and for individual cancer probability. This instrument may help to identify patients who need a surgical procedure.
Dietary modifications in patients receiving miglustat
Authors: Champion H. , Ramaswami U. , Imrie J. , Lachmann R. H. , Gallagher J. , Cox T. M. , Wraith J. E.
Published: September 2010

Weight loss and gastrointestinal disturbances are often seen during miglustat therapy for lysosomal storage diseases. A retrospective analysis of data from a mixed group of patients treated with miglustat at two UK centres was performed to evaluate the effect of two different dietary interventions on body weight and gastrointestinal tolerability during the initial 6 months of miglustat therapy. Neurological outcomes in these patients are not discussed herein. Data were analysed from a total of 29 patients with varied neurolipidoses (21 children/adolescents; 8 adults). Negative mean changes in body weight were seen in children/adolescents on an unmodified diet (−8.1%), and in adults (−4.1%) and children/adolescents (−5.2%) on a low‐lactose diet. Patients on the low‐disaccharide diet showed a positive mean change in body weight (+2.0%), although there was high variability in this group. Non‐parametric sub‐analysis of median body‐weight change in children/adolescents also showed high variability both within and between diet groups, with no statistically significant difference between the effects of different diets on body weight (p = 0.062). The low‐lactose diet reduced gastrointestinal disturbances; single small doses of loperamide were required in some patients. Patients on the low‐disaccharide diet showed the lowest frequency of gastrointestinal effects. In conclusion, simple dietary modifications allowed the maintenance of body‐weight gain in line with normal growth potential during miglustat therapy in young patients with lysosomal storage diseases, and reduced gastrointestinal disturbances.