bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential importance of alterations in hydrogen sulphide (H2S) bioavailability in diabetes
Authors: Lefer D J 
Published: September 2008

Despite its long‐standing reputation as a foul smelling and toxic gas that is associated with the decay of biological matter, hydrogen sulphide (H2S) has emerged as an important regulator of cardiovascular homoeostasis. H2S promotes a number of cellular signals that regulate metabolism, cardiac function and cell survival. Endogenous H2S bioavailability is regulated by several enzymes involved in the biosynthesis of cysteine. This study by Brancaleone et al. in the current issue of the British Journal of Pharmacology provides novel insights into the impairment of H2S biosynthesis in the setting of diabetes mellitus. The authors report that enzymic H2S biosynthesis is impaired in a murine model of type 1 diabetes and the attenuation in H2S bioavailability is associated with impaired vascular reactivity. This study has profound implications for the use of pharmacological agents to augment endogenous H2S synthesis or agents that release H2S to augment the levels of this gaseous signalling molecule in cardiovascular disease.British Journal of Pharmacology (2008) 155, 617–619; doi:fn1; published online 22 September 2008
Identification of α1L‐adrenoceptor in mice and its abolition by α1A‐adrenoceptor gene knockout
Authors: Muramatsu I , Morishima S , Suzuki F , Yoshiki H , Anisuzzaman A S M , Tanaka T , Rodrigo M C , Myagmar B E , Simpson P C 
Published: September 2008

Background and purpose:The α1L‐adrenoceptor has pharmacological properties that distinguish it from three classical α1‐adrenoceptors (α1A, α1Band α1D). The purpose of this was to identify α1L‐adrenoceptors in mice and to examine their relationship to classical α1‐adrenoceptors.Experimental approach:Radioligand binding and functional bioassay experiments were performed on the cerebral cortex, vas deferens and prostate of wild‐type (WT) and α1A‐, α1B‐ and α1D‐adrenoceptor gene knockout (AKO, BKO and DKO) mice.Key results:The radioligand [3H]‐silodosin bound to intact segments of the cerebral cortex, vas deferens and prostate of WT, BKO and DKO but not of AKO mice. The binding sites were composed of two components with high and low affinities for prazosin or RS‐17053, indicating the pharmacological profiles of α1A‐adrenoceptors and α1L‐adrenoceptors. In membrane preparations of WT mouse cortex, however, [3H]‐silodosin bound to a single population of prazosin high‐affinity sites, suggesting the presence of α1A‐adrenoceptors alone. In contrast, [3H]‐prazosin bound to two components having α1A‐adrenoceptor and α1B‐adrenoceptor profiles in intact segments of WT and DKO mouse cortices, but AKO mice lacked α1A‐adrenoceptor profiles and BKO mice lacked α1B‐adrenoceptor profiles. Noradrenaline produced contractions through α1L‐adrenoceptors with low affinity for prazosin in the vas deferens and prostate of WT, BKO and DKO mice. However, the contractions were abolished or markedly attenuated in AKO mice.Conclusions and implications:α1L‐Adrenoceptors were identified as binding and functional entities in WT, BKO and DKO mice but not in AKO mice, suggesting that the α1L‐adrenoceptor is one phenotype derived from the α1A‐adrenoceptor gene.British Journal of Pharmacology(2008)155, 1224–1234; doi:10.1038/bjp.2008.360; published online 22 September 2008
The guinea‐pig tracheal potential difference as an in vivo model for the study of epithelial sodium channel function in the airways
Authors: Coote K J , Atherton H , Young A , Sugar R , Burrows R , Smith N J , Schlaeppi J‐M , Groot‐Kormelink P J , Gosling M , Danahay H 
Published: September 2008

Background and purpose:The epithelial sodium channel (ENaC) is a key regulator of airway mucosal hydration and mucus clearance. Negative regulation of airway ENaC function is predicted to be of clinical benefit in the cystic fibrosis lung. The aim of this study was to develop a small animal model to enable the direct assessment of airway ENaC function in vivo.Experimental approach:Tracheal potential difference (TPD) was utilized as a measure of airway epithelial ion transport in the guinea‐pig. ENaC activity in the trachea was established with a dose–response assessment to a panel of well‐characterized direct and indirect pharmacological modulators of ENaC function, delivered by intra‐tracheal (i.t.) instillation.Key results:The TPD in anaesthetized guinea‐pigs was attenuated by the direct ENaC blockers: amiloride, benzamil and CF552 with ED50 values of 16, 14 and 0.2 μg kg−1 (i.t.), respectively. 5‐(N‐Ethyl‐N‐isopropyl) amiloride, a structurally related compound but devoid of activity on ENaC, was without effect on the TPD. Intra‐tracheal dosing of the Kunitz‐type serine protease inhibitors aprotinin and placental bikunin, which have previously been demonstrated to inhibit proteolytic activation of ENaC, likewise potently attenuated TPD in guinea‐pigs, whereas α1‐antitrypsin and soya bean trypsin inhibitor were without effect.Conclusions and implications:The pharmacological sensitivity of the TPD to amiloride analogues and also to serine protease inhibitors are both consistent with that of ENaC activity in the guinea‐pig trachea. The guinea‐pig TPD therefore represents a suitable in vivo model of human airway epithelial ion transport.British Journal of Pharmacology (2008) 155, 1025–1033; doi:10.1038/bjp.2008.363; published online 22 September 2008
An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption
Authors: Herrera B S , Ohira T , Gao L , Omori K , Yang R , Zhu M , Muscara M N , Serhan C N , Van Dyke T E , Gyurko R 
Published: September 2008

Background and purpose:The inflammation‐resolving lipid mediator resolvin E1 (RvE1) effectively stops inflammation‐induced bone loss in vivo in experimental periodontitis. It was of interest to determine whether RvE1 has direct actions on osteoclast (OC) development and bone resorption.Experimental approach:Primary OC cultures derived from mouse bone marrow were treated with RvE1 and analysed for OC differentiation, cell survival and bone substrate resorption. Receptor binding was measured using radiolabelled RvE1. Nuclear factor (NF)‐κB activation and Akt phosphorylation were determined with western blotting. Lipid mediator production was assessed with liquid chromatography tandem mass spectrometry.Key results:OC growth and resorption pit formation were markedly decreased in the presence of RvE1. OC differentiation was inhibited by RvE1 as demonstrated by decreased number of multinuclear OC, a delay in the time course of OC development and attenuation of receptor activator of NF‐κB ligand‐induced nuclear translocation of the p50 subunit of NF‐κB. OC survival and apoptosis were not altered by RvE1. Messenger RNA for both receptors of RvE1, ChemR23 and BLT1 is expressed in OC cultures. Leukotriene B4 (LTB4) competed with [3H]RvE1 binding on OC cell membrane preparations, and the LTB4 antagonist U75302 prevented RvE1 inhibition of OC growth, indicating that BLT1 mediates RvE1 actions on OC. Primary OC synthesized the RvE1 precursor 18R‐hydroxy‐eicosapentaenoic acid and LTB4. Co‐incubation of OC with peripheral blood neutrophils resulted in transcellular RvE1 biosynthesis.Conclusions and implications:These results indicate that RvE1 inhibits OC growth and bone resorption by interfering with OC differentiation. The bone‐sparing actions of RvE1 are in addition to inflammation resolution, a direct action in bone remodelling.British Journal of Pharmacology (2008) 155, 1214–1223; doi:10.1038/bjp.2008.367; published online 22 September 2008
Benzylidene derivatives of andrographolide inhibit growth of breast and colon cancer cells in vitro by inducing G1 arrest and apoptosis
Authors: Jada S R , Matthews C , Saad M S , Hamzah A S , Lajis N H , Stevens M F G , Stanslas J 
Published: September 2008

Background and purpose:Andrographolide, the major phytoconstituent of Andrographis paniculata, was previously shown by us to have activity against breast cancer. This led to synthesis of new andrographolide analogues to find compounds with better activity than the parent compound. Selected benzylidene derivatives were investigated for their mechanisms of action by studying their effects on the cell cycle progression and cell death.Experimental approach:Microculture tetrazolium, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays were utilized in assessing the in vitro growth inhibition and cytotoxicity of compounds. Flow cytometry was used to analyse the cell cycle distribution of control and treated cells. CDK1 and CDK4 levels were determined by western blotting. Apoptotic cell death was assessed by fluorescence microscopy and flow cytometry.Key results:Compounds, in nanomolar to micromolar concentrations, exhibited growth inhibition and cytotoxicity in MCF‐7 (breast) and HCT‐116 (colon) cancer cells. In the NCI screen, 3,19‐(2‐bromobenzylidene) andrographolide (SRJ09) and 3,19‐(3‐chloro‐4‐fluorobenzylidene) andrographolide (SRJ23) showed greater cytotoxic potency and selectivity than andrographolide. SRJ09 and SRJ23 induced G1 arrest and apoptosis in MCF‐7 and HCT‐116 cells, respectively. SRJ09 downregulated CDK4 but not CDK1 level in MCF‐7 cells. Apoptosis induced by SRJ09 and SRJ23 in HCT‐116 cells was confirmed by annexin V‐FITC/PI flow cytometry analysis.Conclusion and implications:The new benzylidene derivatives of andrographolide are potential anticancer agents. SRJ09 emerged as the lead compound in this study, exhibiting anticancer activity by downregulating CDK4 to promote a G1 phase cell cycle arrest, coupled with induction of apoptosis.British Journal of Pharmacology (2008) 155, 641–654; doi:10.1038/bjp.2008.368; published online 22 September 2008
Use of atorvastatin as an anti‐inflammatory treatment in Crohn's disease
Authors: Grip O , Janciauskiene S , Bredberg A 
Published: September 2008

Background and purpose:Experimental and clinical investigations have revealed that statins can downregulate both acute and chronic inflammatory processes. Whether statins express anti‐inflammatory activities in the treatment of Crohn's disease is unknown.Experimental approach:Ten patients were given 80 mg atorvastatin once daily for 13 weeks and then followed up for 8 weeks after the treatment. The anti‐inflammatory effects of statin were assessed by measuring levels of plasma C‐reactive protein (CRP), soluble (s) CD14, tumour necrosis factor (TNF)‐α, sTNFRI and II, CCL2 and 8 and the mucosal inflammation by faecal calprotectin. Circulating monocytes were subgrouped and their chemokine receptor expression of CCR2 and CX3CR1 were analysed.Key results:In 8 of 10 patients, atorvastatin treatment reduced CRP (P=0.008) and sTNFRII (P=0.064). A slight decrease in plasma levels of sCD14, TNF‐α and sTNFRI was observed in 7/10 patients and faecal calprotectin was reduced in 8/10 patients. We also observed that the treatment diminished expression of CCR2 and CX3CR1 on monocyte populations (P=0.014). At the follow‐up visit, 8 weeks after the atorvastatin treatment was terminated, CRP levels had returned to those seen before the treatment.Conclusions and implications:Our findings imply that atorvastatin therapy reduces inflammation in patients with Crohn's disease and, therefore, encourage further investigations of statin‐mediated protective effects in inflammatory bowel diseases.British Journal of Pharmacology (2008) 155, 1085–1092; doi:10.1038/bjp.2008.369; published online 22 September 2008
Virodhamine relaxes the human pulmonary artery through the endothelial cannabinoid receptor and indirectly through a COX product
Authors: Kozłowska H , Baranowska M , Schlicker E , Kozłowski M , Laudañski J , Malinowska B 
Published: September 2008

Background and purpose:The endocannabinoid virodhamine is a partial agonist at the cannabinoid CB1 receptor and a full agonist at the CB2 receptor, and relaxes rat mesenteric arteries through endothelial cannabinoid receptors. Its concentration in the periphery exceeds that of the endocannabinoid anandamide. Here, we examined the influence of virodhamine on the human pulmonary artery.Experimental approach:Isolated human pulmonary arteries were obtained during resections for lung carcinoma. Vasorelaxant effects of virodhamine were examined on endothelium‐intact vessels precontracted with 5‐HT or KCl.Key results:Virodhamine, unlike WIN 55,212‐2, relaxed 5‐HT‐precontracted vessels concentration dependently. The effect of virodhamine was reduced by endothelium denudation, two antagonists of the endothelial cannabinoid receptor, cannabidiol and O‐1918, and a high concentration of the CB1 receptor antagonist rimonabant (5 μM), but only slightly attenuated by the NOS inhibitor L‐NAME and not affected by a lower concentration of rimonabant (100 nM) or by the CB2 and vanilloid receptor antagonists SR 144528 and capsazepine, respectively. The COX inhibitor indomethacin and the fatty acid amide hydrolase inhibitor URB597 and combined administration of selective blockers of small (apamin) and intermediate and large (charybdotoxin) conductance Ca2+‐activated K+ channels attenuated virodhamine‐induced relaxation. The vasorelaxant potency of virodhamine was lower in KCl‐ than in 5‐HT‐precontracted preparations.Conclusions and implications:Virodhamine relaxes the human pulmonary artery through the putative endothelial cannabinoid receptor and indirectly through a COX‐derived vasorelaxant prostanoid formed from the virodhamine metabolite, arachidonic acid. One or both of these mechanisms may stimulate vasorelaxant Ca2+‐activated K+ channels.British Journal of Pharmacology (2008) 155, 1034–1042; doi:10.1038/bjp.2008.371; published online 22 September 2008
The Effect of Temporal Gap Identification on Speech Perception by Users of Cochlear Implants
Authors: Sagi Elad , Kaiser Adam R. , Meyer Ted A. , Svirsky Mario A. 
Published: September 2008

Purpose
This study examined the ability of listeners using cochlear implants (CIs) and listeners with normal hearing (NH) to identify silent gaps of different duration and the relation of this ability to speech understanding in CI users.

Method

Sixteen NH adults and 11 postlingually deafened adults with CIs identified synthetic vowel-like stimuli that were either continuous or contained an intervening silent gap ranging from 15 ms to 90 ms. Cumulative
d'
, an index of discriminability, was calculated for each participant. Consonant and consonant–nucleus–consonant (CNC) word identification tasks were administered to the CI group.

Results

Overall, the ability to identify stimuli with gaps of different duration was better for the NH group than for the CI group. Seven CI users had cumulative
d'
scores that were no higher than those of any NH listener, and their CNC word scores ranged from 0% to 30%. The other 4 CI users had cumulative
d'
scores within the range of the NH group, and their CNC word scores ranged from 46% to 68%. For the CI group, cumulative
d'
scores were significantly correlated with their speech testing scores.

Conclusions
The ability to identify silent gap duration may help explain individual differences in speech perception by CI users.
MS-BID: a Java package for label-free LC-MS-based comparative proteomic analysis
Authors: Hwang Daehee , Zhang Ning , Lee Hookeun , Yi Eugene , Zhang Hui , Lee Inyoul Y. , Hood Leroy , Aebersold Ruedi 
Published: September 2008

Abstract
Summary: MS-BID (MS Biomarker Discovery Platform) is an integrative computational pipeline for biomarker discovery using LC-MS-based comparative proteomic analysis. This platform consists of several computational tools for: (i) detecting peptides in the collected patterns; (ii) matching detected peptides across a number of LC-MS datasets and (iii) selecting discriminatory peptides between classes of samples.
Availability: MS-BID source codes, binaries and documentations are freely available under LGPL from http://tools.proteomecenter.org/msBID.php.
Contact: dhhwang@postech.ac.kr
MAP20, a Microtubule-Associated Protein in the Secondary Cell Walls of Hybrid Aspen, Is a Target of the Cellulose Synthesis Inhibitor 2,6-Dichlorobenzonitrile
Authors: Rajangam Alex S. , Kumar Manoj , Aspeborg Henrik , Guerriero Gea , Arvestad Lars , Pansri Podjamas , Brown Christian J.-L. , Hober Sophia , Blomqvist Kristina , Divne Christina , Ezcurra Ines , Mellerowicz Ewa , Sundberg Björn , Bulone Vincent , Teeri Tuula T. 
Published: September 2008

AbstractWe have identified a gene, denoted PttMAP20, which is strongly up-regulated during secondary cell wall synthesis and tightly coregulated with the secondary wall-associated CESA genes in hybrid aspen (Populus tremula × tremuloides). Immunolocalization studies with affinity-purified antibodies specific for PttMAP20 revealed that the protein is found in all cell types in developing xylem and that it is most abundant in cells forming secondary cell walls. This PttMAP20 protein sequence contains a highly conserved TPX2 domain first identified in a microtubule-associated protein (MAP) in Xenopus laevis. Overexpression of PttMAP20 in Arabidopsis (Arabidopsis thaliana) leads to helical twisting of epidermal cells, frequently associated with MAPs. In addition, a PttMAP20-yellow fluorescent protein fusion protein expressed in tobacco (Nicotiana tabacum) leaves localizes to microtubules in leaf epidermal pavement cells. Recombinant PttMAP20 expressed in Escherichia coli also binds specifically to in vitro-assembled, taxol-stabilized bovine microtubules. Finally, the herbicide 2,6-dichlorobenzonitrile, which inhibits cellulose synthesis in plants, was found to bind specifically to PttMAP20. Together with the known function of cortical microtubules in orienting cellulose microfibrils, these observations suggest that PttMAP20 has a role in cellulose biosynthesis.
The effects of structural variation in some isoxazolidines on the corrosion inhibition of carbon steel in 0.5 M sulfuric acid
Authors: Al‐Ghamdi R.F. , El‐Shareef A.M. , Saeed M.T. , Ali S.A. 
Published: September 2008

PurposeThe aim is to demonstrate corrosion inhibition capabilities of several isoxazolidines, containing hydrophobic substituents and having varying degree of steric congestion around nitrogen.Design/methodology/approachA number of isoxazolidines were prepared. Corrosion inhibition efficiencies of these organic compounds were determined by gravimetric and electrochemical methods, using carbon steel as the substrate metal and 0.5 M H2SO4 at 40‐70°C as the corrosive environment. Concentration of inhibitor was varied between 5 and 400 ppm.FindingsIncrease in steric congestion around the nitrogen centre and hydrophobic chain lengths as well as increase in temperature (in the presence of the inhibitor in the higher concentration range 100‐400 ppm) were found to increase the corrosion inhibition efficiency of the isoxazolidines. Electrochemical measurements corroborated these results. Thermodynamic parameters (ΔGads0,ΔHads0,ΔSads0) for the adsorption process and kinetic parameters for the metal dissolution (or hydrogen evolution) reaction were determined.Originality/valueThis is the first time the corrosion inhibition characteristics of isoxazolidines, an important class of readily accessible compounds, have been evaluated in H2SO4 medium.
Turkish academic staffs' perception of organic foods
Authors: Özfer Özc¸elik Ays¸e , Uçar Asli 
Published: September 2008

PurposeThis study was planned and carried out among the academic staff working in Ankara (Turkey) in order to determine their perception of organic foods.Design/methodology/approachA total of 240 academicians from three institutes at the Ankara University were selected to participate in the research. Data were collected through a survey questionnaire, in which a Likert type scale was used to determine the perception of organic foods. The institutes where the academic staff work are considered as the variables in the study (science, health sciences, and social sciences).FindingsThe research results indicated that there was a significant correlation between the institutes and academicians agreement with 12 statements in the survey questionnaire. Considering the institute variable, no significant difference was found in the organic foods perceptions of individuals from different institutes.Originality/valueOrganic products are widely on the market today. Consumer demand for organic foods has been steadily rising worldwide. Organic food consumption has slightly increased in Turkey in recent years, too. Still, many Turkish consumers do not have enough knowledge about organic foods yet. This study is valuable in that it explores at least some of the Turkish consumers' perception of organic foods whose consumption in the world is increasing fast.
Acceptance of genetically modified food in India: perspectives of gatekeepers
Authors: Knight John , Paradkar Amit 
Published: September 2008

PurposeConsumer and public policy resistance to genetically modified (GM) foods in rich countries has caused governments in many poor countries to withhold official permission for planting GM food crops for fear of damaging export markets for conventional crops. A total of 15 countries are already producing GM food crops. If China and India, the world's two most populous nations, authorise GM food production, then this will account for a large majority of the world's food production coming from GM‐adopting countries. This study sets out to determine perceptions of gatekeepers of the food distribution channel in India towards GM foods.Design/methodology/approachPersonal interviews were conducted with key informants of a convenience sample of twenty gatekeepers of the food distribution channel in seven main commercial centres in the India. In addition, three agricultural scientists prominent in new crop development in India were interviewed to provide perspectives of likely current and future developments.FindingsAccording to gatekeepers interviewed, the GM issue has not achieved great prominence in India, and the public generally seem oblivious to the issue. Activist opposition has been to foreign companies gaining monopoly rights over intellectual property, rather than to GM foods per se. Crop scientists interviewed indicated that biotechnology is widely regarded by the Indian Government as providing the means for a second green revolution. Current Indian government policy appears to be to speed up research and development of a wide range of GM food crops.Originality/valueThese findings are important to public policy makers in food exporting countries as they point to the likelihood of adoption of GM technology in the world's second most populous market.