bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crocus sativus L. in the treatment of mild to moderate depression: a double‐blind, randomized and placebo‐controlled trial
Authors: Akhondzadeh Shahin , Tahmacebi‐Pour Najaf , Noorbala Ahamad‐Ali , Amini Homayoun , Fallah‐Pour Hassan , Jamshidi Amir‐Hossein , Khani Mousa 
Published: April 2005

AbstractDepression is a serious disorder in today's society, with estimates of lifetime prevalence as high as 21% of the general population in some developed countries. As a therapeutic plant, saffron is considered excellent for stomach ailments and as an antispasmodic, to help digestion and to increase appetite. It is also used for depression in Persian traditional medicine. Our objective was to assess the efficacy of the stigmas of Crocus sativus (saffron) in the treatment of mild to moderate depression in a 6‐week double‐blind, placebo‐controlled and randomized trial.Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients had a baseline Hamilton rating scale for depression score of at least 18. In this double‐blind, placebo‐controlled, single‐centre and randomized trial, patients were randomly assigned to receive a capsule of saffron 30 mg[sol ]day (BD) (Group 1) or a capsule of placebo (BD) (Group 2) for a 6‐week study. At 6 weeks, Crocus sativus produced a significantly better outcome on the Hamilton depression rating scale than the placebo (d.f. = 1, F = 18.89, p < 0.001). There were no significant differences in the two groups in terms of the observed side effects.The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large‐scale trial is justified. Copyright © 2005 John Wiley & Sons, Ltd.
Evaluation of antiprotozoal and plasmodial enoyl‐ACP reductase inhibition potential of turkish medicinal plants
Authors: Tasdemir D. , Brun R. , Perozzo R. , Dönmez A. A. 
Published: April 2005

AbstractA total of 58 extracts of different polarity were prepared from various organs of 16 species of Turkish plants and screened for their antitrypanosomal, antileishmanial and antiplasmodial activities. No significant activity was observed against Trypanosoma cruzi, whereas many extracts showed appreciable trypanocidal potential against T. brucei rhodesiense, with the CHCl3‐soluble portion of Phlomis kurdica being the most active (IC50 2.7 µg[sol ]mL). Almost all extracts, particularly the CHCl3 phases, exhibited growth inhibition activity against Leishmania donovani amastigotes. The CHCl3‐solubles of Putoria calabrica roots (IC50 1.9 µg[sol ]mL), Wendlandia ligustroides leaves (IC50 2.1 µg[sol ]mL) and Rhododendron luteum leaves (IC50 2.3 µg[sol ]mL) displayed the highest leishmanicidal potential. The majority of the extracts also possessed antiplasmodial activity against the multi‐drug resistant K1 Plasmodium falciparum strain. The most potent antiplasmodial activity was observed with the CHCl3 extracts of Phlomis kurdica (IC50 1.5 µg[sol ]mL), P. leucophracta (IC50 1.6 µg[sol ]mL), Scrophularia cryptophila (IC50 1.8 µg[sol ]mL), Morina persica (IC50 1.9 µg[sol ]mL) and the aqueous root extract of Asperula nitida subsp. subcapitellata (IC50 1.6 µg[sol ]mL). Twenty‐one extracts with significant antimalarial activity (IC50 < 5 µg[sol ]mL) were also tested for their ability to inhibit the purified enoyl‐ACP reductase (FabI), a crucial enzyme in the fatty acid biosynthesis of P. falciparum. The CHCl3 extract of Rhododendron ungernii leaves (IC50 10 µg[sol ]mL) and the H2O‐soluble portion of Rhododendron smirnovii leaves (IC50 0.4 µg[sol ]mL) strongly inhibited the FabI enzyme. The preliminary data indicate that some (poly)phenolic compounds are responsible for the FabI inhibition potential of these extracts. The presented work reports for the first time the antiprotozoal activity of nine different genera as well as a target specific antimalarial screening for the identification of P. falciparum FabI inhibitors from medicinal plant extracts. Copyright © 2005 John Wiley & Sons, Ltd.
Siberian ginseng reduces infarct volume in transient focal cerebral ischaemia in Sprague‐Dawley rats
Authors: Bu Yungmin , Jin Zhen Hua , Park Sun Young , Baek Sunkyung , Rho Sungju , Ha Nina , Park Seong Kyu , Sun Yeo Kim  , Kim Hocheol 
Published: April 2005

AbstractSiberian ginseng, the root and stem bark of Acanthopanax senticosus Harms, has been used as a tonic and adaptogen to strengthen qi in traditional Korean medicine. The neuroprotective effects of water extracts of A. senticosus (ASW) were investigated in transient middle cerebral artery occlusion (MCAo, 90 min occlusion, 24 h reperfusion) of Sprague‐Dawley rats. The infarct volume was significantly reduced by 36.6% after the peritoneal injection of ASW (100 mg[sol ]kg) compared with the control. In the immunohistochemical study, ASW markedly inhibited both cyclooxygenase‐2 and OX‐42 expressions in the penumbral region at 24 h after MCAo. These results suggest that A. senticosus has a neuroprotective effect by inhibiting inflammation and microglial activation in brain ischaemia. Copyright © 2005 John Wiley & Sons, Ltd.
Ionization potentials of MgO clusters containing a substitutional atom
Authors: Coudray C. 
Published: April 2005

AbstractWith the help of a DFT‐LDA method, computations of the ionization potentials of MgO clusters were made. Starting from (5 × 5 × 5) cubic pieces of a crystal, these clusters were obtained by optimization. In order to study the influence of a substitutional atom, their central atom—either Mg or O—was removed and replaced by other atoms of different valences. These clusters were charged in order to reproduce the density of states of a neutral crystal (full valence band, empty conduction band), then one and two electrons were successively added and removed. When the substitutional atom does not give rise to an impurity level in the bandgap, a linear law of the ionization potentials with respect to the valence of this atom was observed. This law results from the Coulomb interaction between the cluster and the electrons and from the structure of the density of states of the cluster. This allows us to foresee the values of the ionization potentials of an MgO cluster possessing a substitutional atom, according to the valence of this atom. A similar law would probably appear in any cluster of a crystalline insulator. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Theoretical investigation of weakly interacting molecular systems using the virial theorem
Authors: Kozmutza Cornelia , Tfirst Ernő 
Published: April 2005

AbstractIn this work we examine some H‐bonded systems using the method of separated molecular orbitals (SMOs) at the Hartree‐Fock level. Several geometry‐optimized configurations of the water hexamer were chosen for the study. The energetic components for the monomers in the whole structures and also in the contributing subunits of the supersystems were calculated. Five different basis sets were applied and the fulfillment of the virial theorem was assessed. A two‐parameter geometry dependence of these energetic components in a model water dimer was also investigated. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Generation of the C2H3O+ ion in reactions of O(3P) with 2‐butyne
Authors: Metropoulos Aristophanes 
Published: April 2005

AbstractWe investigated the feasibility of formation of the C2H3O+ chemiion during collisions of O(3P) with the CH3C (ã4A2), CH2CH (ã4A″), CH3C (X2A″), and CH2CH (X2A′) radicals, which are possible intermediates in the oxidation of 2‐butyne. We determined the C–O bond dissociation energies and the ionization energies of the neutral C2H3O species as well as the C–O bond dissociation energies of C2H3O+. We conclude that the CH3C (ã4A2) radical is the most probable precursor of the chemiion, in agreement with experimental evidence. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
COMPUTER LEARNER CORPORA, SECOND LANGUAGE ACQUISITION, AND FOREIGN
LANGUAGE TEACHING
Authors: Zwier Lawrence J. 
Published: April 2005

COMPUTER LEARNER CORPORA, SECOND LANGUAGE ACQUISITION, AND FOREIGN
LANGUAGE TEACHING. Sylviane Granger, Joseph Hung, and Stephanie
Petch-Tyson (Eds.). Amsterdam: Benjamins, 2002. Pp. x + 246.
$42.95 paper.Insights derived from language corpora have influenced countless
aspects of language teaching, testing, research, and materials
development. Granger, Hung, and Petch-Tyson have created an
indispensable testament to the specific value of corpora in SLA
research. A great virtue of this volume is that the corpus is treated
as a tool, and the tool does not distract from the job at hand. The
focus is where it should be—on features of native language,
interlanguage, and target language as elucidated by corpus-based study.
The corpora stand in the background, ready to serve.
BILINGUALISM: BEYOND BASIC PRINCIPLES
Authors: Cenoz Jasone 
Published: April 2005

BILINGUALISM: BEYOND BASIC PRINCIPLES. Jean-Marc Dewaele, Alex
Housen, and Li Wei (Eds.). Clevedon, UK: Multilingual Matters,
2003. Pp. ix +233. £49.90 cloth, £22.95 paper.This volume is a festschrift in honor of Hugo Baetens Beardsmore on
the occasion of his sixtieth birthday and the twentieth anniversary of
the publication of his book Bilingualism: Basic principles
(1982). The volume includes 12 articles in addition to an introduction
and a laudatio. The volume reflects the important developments of
studies in bilingualism in the last 20 years and covers a great variety
of areas related to the sociolinguistic, educational, and
psycholinguistic dimensions of bilingualism. The first chapter is a
reprint of one of Baetens Beardsmore's lesser known publications
(1988) and discusses the fears of bilingualism at different levels.
Fifteen years later, this chapter still addresses the most important
issues related to bilingualism often discussed by teachers, parents,
and policy makers. The next three chapters focus on the social aspects
of bilingualism: Edwards discusses bilingualism and identity in chapter
2, Clyne addresses the role of intrinsic motivation and metalinguistic
awareness in bilingualism in chapter 3, and Cummins examines the
differences between the criticism against bilingual education in the
American press and the positive results of research on the outcomes of
bilingualism in chapter 4. These three chapters each have a different
focus but taken together provide an interesting perspective of the
social factors affecting bilingualism. Chapter 5 by Martin and chapter
7 by Jones discuss multilingual education in Brunei. These two chapters
describe the languages used in schools, the educational context, and
the most recent changes in education in Brunei and could be of interest
for educators in other bilingual contexts. Chapter 6 by Baker and
chapter 8 by Wei and Milroy both discuss language and society but focus
on minority languages in two completely different settings—Wales
and Singapore. Both chapters discuss interesting theoretical aspects
that are then applied to specific settings. Chapter 9 (Fraser Gupta)
has a very weak link to the rest of the chapters in the book and
analyzes seven self-study books of Malay from different periods.
Chapter 10 (Lüdi) and chapter 11 (Myers-Scotton) discuss
interesting theoretical aspects of codeswitching, and the last chapter
(Genesee) focuses on the similarities and differences between early
monolingual and bilingual acquisition. These three chapters are more
research oriented than the rest of the chapters in the book, both
because of their theoretical basis and the empirical data they discuss.
They may also be the most interesting for researchers in SLA.
Mechanisms underlying the relaxation response induced by bradykinin in the epithelium‐intact guinea‐pig trachea in vitro
Authors: Schlemper Valfredo , Medeiros Rodrigo , Ferreira Juliano , Campos Maria M , Calixto João B 
Published: April 2005

In this study, we investigated some of the signalling pathways involved in bradykinin (BK)‐induced relaxation in epithelium‐intact strips of the guinea‐pig trachea (GPT+E). BK induced time‐ and concentration‐dependent relaxation of GPT+E. Similar responses were observed for prostaglandin E2 (PGE2) or the combination of subthreshold concentrations of BK plus PGE2.
The nonselective cyclooxygenase (COX) inhibitors indomethacin or pyroxicam, or the selective COX‐2 inhibitors DFU, NS 398 or rofecoxib, but not the selective COX‐1 inhibitor SC 560, all abolished BK‐induced relaxation.
The tyrosine kinase inhibitors herbimycin A and AG 490 also abolished BK‐induced relaxation in GPT+E.
The nonselective nitric oxide synthase (NOS) inhibitor 7‐NINA concentration‐dependently inhibited BK effects.
BK‐induced relaxation was prevented by the selective antagonists for EP3 (L 826266), but not by EP1 (SC 19221), EP1/EP2 (AH 6809) or EP4 (L 161982) receptor antagonists.
Otherwise, the selective inhibitors of protein kinases A, G and C, mitogen‐activated protein kinases, phospholipases C and A2, nuclear factor‐κB or potassium channels all failed to significantly interfere with BK‐mediated relaxation.
BK caused a marked increase in PGE2 levels, an effect that was prevented by NS 398, HOE 140 or AG 490.
COX‐2 expression did not differ in preparations with or without epithelium, and it was not changed by BK stimulation. However, incubation with BK significantly increased the endothelial NOS (eNOS) and neuronal NOS (nNOS) expression, independent of the epithelium integrity.
Our results indicate that BK‐induced relaxation in GPT+E depends on prostanoids (probably PGE2 acting via EP3 receptors) and NO release and seems to involve complex interactions between kinin B2 receptors, COX‐2, nNOS, eNOS and tyrosine kinases.

British Journal of Pharmacology (2005) 145, 740–750. doi:10.1038/sj.bjp.0706222
The involvement of nitric oxide in the enhanced expression of μ‐opioid receptors during intestinal inflammation in mice
Authors: Pol Olga , Sasaki Masayuki , Jiménez Natàlia , Dawson Valina L , Dawson Ted M , Puig Margarita M 
Published: April 2005

Intestinal inflammation enhances the potency of μ‐opioid receptor (MOR) agonists inhibiting gastrointestinal transit and increases the expression of MOR in mice intestine. The precise mechanisms implicated in the increased expression of MOR during intestinal inflammation are not known. The aim of the study is to evaluate if nitric oxide released during intestinal inflammation could modulate MOR gene expression and affect gastrointestinal transit.
Intestinal inflammation was induced by the intragastric administration of croton oil. In CD‐1 mice, with and without inflammation, we evaluated the antitransit effects of morphine in animals treated with NOS inhibitors (L‐NAME and L‐NIL) and the intestinal levels of iNOS enzyme mRNA. The antitransit effects of morphine and the expression of MOR mRNA in the gut of wild‐type (WT) and iNOS−/− mice were also assessed. Gastrointestinal transit was measured with charcoal meal and mRNA levels determined by real‐time PCR.
In CD‐1 mice, inflammation induced a 10‐fold increase (P<0.0001) in iNOS mRNA levels in the gut. The absence of iNOS gene and treatment of CD‐1 mice with L‐NAME or L‐NIL abolished the increased antitransit effects of morphine observed during inflammation. Moreover, although the basal levels of MOR mRNA were similar in WT and iNOS animals (−/−), intestinal inflammation only increased the MOR expression in the gut of WT (P<0.01) but not in iNOS−/− mice.
The results suggest that nitric oxide derived from the increased expression of iNOS is implicated in the enhanced effects of morphine and in the upregulation of MOR gene transcription observed during intestinal inflammation.

British Journal of Pharmacology (2005) 145, 758–766. doi:10.1038/sj.bjp.0706227
Nonpeptidic urotensin‐II receptor antagonists I: in vitro pharmacological characterization of SB‐706375
Authors: Douglas Stephen A , Behm David J , Aiyar Nambi V , Naselsky Diane , Disa Jyoti , Brooks David P , Ohlstein Eliot H , Gleason John G , Sarau Henry M , Foley James J , Buckley Peter T , Schmidt Dulcie B , Wixted William E , Widdowson Katherine , Riley Graham , Jin Jian , Gallagher Timothy F , Schmidt Stanley J , Ridgers Lance , Christmann Lisa T , Keenan Richard M , Knight Steven D , Dhanak Dashyant 
Published: April 2005

SB‐706375 potently inhibited [125I]hU‐II binding to both mammalian recombinant and ‘native’ UT receptors (Ki 4.7±1.5 to 20.7±3.6 nM at rodent, feline and primate recombinant UT receptors and Ki 5.4±0.4 nM at the endogenous UT receptor in SJRH30 cells).
Prior exposure to SB‐706375 (1 μM, 30 min) did not alter [125I]hU‐II binding affinity or density in recombinant cells (KD 3.1±0.4 vs 5.8±0.9 nM and Bmax 3.1±1.0 vs 2.8±0.8 pmol mg−1) consistent with a reversible mode of action.
The novel, nonpeptidic radioligand [3H]SB‐657510, a close analogue of SB‐706375, bound to the monkey UT receptor (KD 2.6±0.4 nM, Bmax 0.86±0.12 pmol mg−1) in a manner that was inhibited by both U‐II isopeptides and SB‐706375 (Ki 4.6±1.4 to 17.6±5.4 nM) consistent with the sulphonamides and native U‐II ligands sharing a common UT receptor binding domain.
SB‐706375 was a potent, competitive hU‐II antagonist across species with pKb 7.29–8.00 in HEK293‐UT receptor cells (inhibition of [Ca2+]i‐mobilization) and pKb 7.47 in rat isolated aorta (inhibition of contraction). SB‐706375 also reversed tone established in the rat aorta by prior exposure to hU‐II (Kapp∼20 nM).
SB‐706375 was a selective U‐II antagonist with 100‐fold selectivity for the human UT receptor compared to 86 distinct receptors, ion channels, enzymes, transporters and nuclear hormones (Ki/IC50>1 μM). Accordingly, the contractile responses induced in isolated aortae by KCl, phenylephrine, angiotensin II and endothelin‐1 were unaltered by SB‐706375 (1 μM).
In summary, SB‐706375 is a high‐affinity, surmountable, reversible and selective nonpeptide UT receptor antagonist with cross‐species activity that will assist in delineating the pathophysiological actions of U‐II in mammals.

British Journal of Pharmacology (2005) 145, 620–635. doi:10.1038/sj.bjp.0706229
Identification of WIN55212‐3 as a competitive neutral antagonist of the human cannabinoid CB2 receptor
Authors: Savinainen Juha R , Kokkola Tarja , Salo Outi M H , Poso Antti , Järvinen Tomi , Laitinen Jarmo T 
Published: April 2005

Several G protein‐coupled receptors (GPCRs), including cannabinoid CB1 and CB2 receptors, show constitutive activity under heterologous expression. Such a tonic response is generated in the absence of an activating ligand, and can be inhibited by inverse agonists. Neutral antagonists, however, are silent at such receptors, but can reverse both agonist and inverse agonist responses. To date, no neutral antagonist for the CB2 receptor has been reported.
Here, by monitoring receptor‐dependent G protein activation, we demonstrate that WIN55212‐3 acts as a neutral antagonist at the human CB2 (hCB2) receptor. WIN55212‐3 alone, at concentrations 10−4 M, behaved as a silent ligand exhibiting no agonist or inverse agonist activity. However, WIN55212‐3 competitively antagonized cannabinoid agonist CP‐55,940‐stimulated responses (pA2 6.1). Importantly, the inverse agonism evoked by SR144528 in hCB2 was dose‐dependently reversed by WIN55212‐3 (pEC50 5.3±0.2), indicating true neutral antagonist behavior.
Furthermore, WIN55212‐3 also antagonized CB1 receptor signaling in a competitive manner (pA2 5.6), but behaved as a partial inverse agonist (pIC50 5.5±0.1) at the constitutively active human CB1.
Additionally, WIN55212‐3 antagonized signaling of the human melatonin MT1 receptor, with modest activity at the human muscarinic M4 receptor, but it was inactive towards several other GPCRs.
These data identify WIN55212‐3 as a true neutral hCB2 receptor antagonist. WIN55212‐3 offers a valuable tool for further characterization of ligand activities at the CB2 receptor and may serve as a lead compound in further efforts to develop more potent and selective neutral CB2 receptor antagonists.

British Journal of Pharmacology (2005) 145, 636–645. doi:10.1038/sj.bjp.0706230
Prednisolone augments superoxide formation in porcine pulmonary artery endothelial cells through differential effects on the expression of nitric oxide synthase and NADPH oxidase
Authors: Muzaffar Saima , Shukla Nilima , Angelini Gianni D , Jeremy Jamie Y 
Published: April 2005

Prednisolone, a potent anti‐inflammatory drug, has proved ineffective in treating acute respiratory distress syndrome (ARDS). ARDS is associated with superoxide (O2•−) generation, which negates nitric oxide (NO). NO also downregulates NADPH oxidase and inhibits O2•− formation. A possible reason for the lack of effect of prednisolone may due to an inhibition of eNOS expression. In order to test this proposal, the effect of prednisolone on O2•− formation and the expression of gp91phox (catalytic subunit of NADPH oxidase) and eNOS in pig pulmonary artery (PA) segments and PA endothelial cells (PAECs) and PA vascular smooth muscle cells (PAVSMCs) was investigated.
PA segments and cells were incubated with prednisolone and tumour necrosis factor‐alpha (TNF‐α) for 16 h. O2•− formation was measured spectrophometrically and gp91phox and eNOS expression by Western blotting. The role of the NO–cGMP axis was studied using morpholinosydnonimine hydrochloride, the diethylamine/NO complex (DETA‐NONOate), the guanylyl cyclase inhibitor, 1H‐{1,2,4}oxadiazolo{4,3‐a}quinoxalin‐1‐one (ODQ) and the stable cGMP analogues, 8‐bromo cGMP and 8‐(4‐chlorophenylthio)‐cGMP (8‐pCPT‐cGMP). NO release was studied using a fluorescence assay and O2•−–NO interactions with a nitrite/nitrate assay.
Prednisolone elicited significant increase in O2•− formation in intact PA segments and PAECs, but not PAVSMCs, in a concentration‐dependent manner. In endothelium‐denuded segments, prednisolone slightly enhanced O2•− release. TNF‐α further increased prednisolone‐enhanced O2•− formation in intact PA segments and PAECs. NADPH oxidase inhibitor, apocynin, inhibited O2•− formation. Increased O2•− release and gp91phox expression in PAECs elicited by prednisolone was blocked by SIN‐1 (3‐morpholinosydnonimine hydrochloride), DETA‐NONOate, 8‐pCPT‐cGMP and 8‐bromo cGMP. The effects of SIN‐1 on gp91phox expression were reversed by ODQ. Finally, eNOS protein expression was significantly reduced by prednisolone.
Prednisolone increases O2•− in porcine PAECs through a downregulation of endogenous eNOS expression. Since the NO–cGMP axis inhibits gp91phox expression, the resultant decrease in endogenous NO formation then augments NADPH oxidase activity, which in turn results in increased O2•− formation. Since O2•− promotes inflammation, this mechanism may explain why prednisolone is ineffective in treating ARDS. Therapeutically, the coadministration of an NO donor may render prednisolone more effective in treating ARDS.

British Journal of Pharmacology (2005) 145, 688–697. doi:10.1038/sj.bjp.0706235