bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of human neutrophil‐mediated cartilage damage in vitro: The role of lysosomal enzymes, hydrogen peroxide and hypochlorous acid
Authors: Kowanko IC , Bates EJ , Ferrante A 
Published: July 2007

SummaryCartilage is a focal point of attack by cellular and molecular elements of the inflammatory response which occurs in arthritic diseases. Neutrophils damage articular cartilage by degrading matrix components and inhibiting their synthesis. The aim of this study was to elucidate mechanisms of this damage. Human neutrophils were isolated from blood by centrifuging through Ficoll‐Hypaque and granule extract prepared from them. Articular cartilage from adult humans and cattle was maintained in organ culture. Cartilage degradation (release of 35S‐labelled proteoglycan) or synthesis (incorporation of 35S into proteoglycan) was determined after various treatments. Human neutrophils and neutrophil granule extract degraded proteoglycan and inhibited proteoglycan synthesis. The specific leucocyte elastase inhibitor N‐methoxysuccinyl‐(ala)2‐pro‐val‐chloromethylketone (MAAPVCMK) partially reversed these effects. H2O2, a product of the neutrophil respiratory burst, when added directly at 10‐6 mol/L, or generated by glucose oxidase (GO)/glucose inhibited proteoglycan synthesis but had no effect on degradation. Hypochlorous acid (OHCl), a product of the myeloperoxidase (MPO)/H2O2/Cl system at 50 μmol/L degraded proteoglycan and inhibited its synthesis. OHCl, produced by granule extract (as a source of MPO) + GO‐generated H2O2 + Cl− degraded proteoglycan. The results indicate that neutrophil‐mediated proteoglycan degradation and inhibition of synthesis is largely attributable to elastase and secondarily to OHCl, whereas H2O2 impairs synthesis without affecting degradation of proteoglycan.
IgG subclasses responsible for immune clearance in mice infected with Trypanosoma cruzi
Authors: Brodskyn CI , Silva AMM , Takehara HA , Mota I 
Published: July 2007

SummaryTo examine the role of different immunoglobulin subclasses in the immune clearance of Trypanosoma cruzi, mice containing bloodstream trypomastigotes were injected intravenously with immune serum, IgG‐depleted serum, or with the IgG1 or IgG2 fractions and the rate of removal oft he parasites from circulation was determined. Using IgG concentrations similar to those found in the immune serum, the rate of clearance mediated by IgG2 was six‐fold higher than that obtained with IgG1. This difference did not appear to be due to differences in antibody specificity, as Western blotting showed that each isotype recognized a similar set of antigens extracted from the parasite. However, the T. cruzi specific antibody content of the IgG2 was approximately five‐fold higher than IgG1. When the dose of IgG was adjusted to equalize the antibody content, the clearance ability of the IgG1 and IgG2 was very similar. It is concluded that the two subclasses have a similar clearance ability.
Role of intestinal immunization in urinary tract defence
Authors: Husband Alan J , Clifton Vicki L 
Published: July 2007

SummaryThe lack of progress in development of vaccines to stimulate local protection in the urinary tract is attributable in part to the lack of information regarding mechanisms of local immunity and to the difficulty in antigen administration at this site. Experiments reported in this paper indicate that the urinary tract in rats forms part of an effector network linking mucosal organs (the common mucosal immune system). Concomitant immunization of the intestine and urinary tract with ovalbumin resulted in the appearance at both sites of antiovalbumin‐containing cells (ACC) of IgA specificity. The gut origin of ACC in the urinary tract was confirmed by demonstrating in similarly immunized rats abrogation of the urinary tract response by chronic drainage of the thoracic lymphatic duct during the post‐challenge period and by demonstrating the appearance of radiolabelled ACC in the urinary tract after injection of labelled autologous thoracic duct lymphocytes collected during the post‐challenge period. These experiments indicate a role for oral immunization in enhancing the local antibody response in the urinary tract against invading pathogens.
The generation and activation of memory class I MHC restricted cytotoxic T cell responses to influenza A virus in vivo do not require CD4+ T cells
Authors: Liu Y , Müllbacher A 
Published: July 2007

SummaryThe cellular requirements for the generation and activation of anti‐influenza memory class I MHC restricted Tc cell responses were studied by selectively reconstituting lethally irradiated mice. The generation of memory Tc cells was investigated by using unprimed splenocytes to reconstitute infected, lethally irradiated mice; the activation of memory Tc cells was tested by using primed splenocytes to reconstitute uninfected, lethally irradiated mice. It is shown here that depletion of CD4+ T cells from donor cells did not reduce Tc cell responses in recipient mice. Depletion of CD8+ T cells from donor splenocytes prevented the memory Tc cell responses. Thus depletion of CD4+ T cells had no effect on the generation and activation of the memory Tc cells in vivo.
1‐Methylnicotinamide (MNA), a primary metabolite of nicotinamide, exerts anti‐thrombotic activity mediated by a cyclooxygenase‐2/prostacyclin pathway
Authors: Chlopicki S , Swies J , Mogielnicki A , Buczko W , Bartus M , Lomnicka M , Adamus J , Gebicki J 
Published: July 2007

Background and purpose:1‐methylnicotinamide (MNA) has been considered to be an inactive metabolite of nicotinamide. Here we assessed the anti‐thrombotic activity of MNA in vivo.Experimental approach:Antithrombotic action of MNA was studied in normotensive rats with extracorporeal thrombus formation (thrombolysis), in renovascular hypertensive rats with intraarterial thrombus formation (arterial thrombosis) and in a venous thrombosis model in rats (venous thrombosis).Key results:MNA (3‐100 mg kg−1) induced a dose‐dependent and sustained thrombolytic response, associated with a rise in 6‐keto‐PGF1α in blood. Various compounds structurally related to MNA were either inactive or weaker thrombolytics. Rofecoxib (0.01‐1 mg kg−1), dose‐dependently inhibited the thrombolytic response of MNA, indomethacin (5 mg kg−1) abolished it, while L‐NAME (5 mg kg−1) were without effect. MNA (3–30 mg kg−1) also reduced arterial thrombosis and this effect was abrogated by indomethacin (2.5 mg kg−1) as well as by rofecoxib (1 mg kg−1). MNA, however, did not affect venous thrombosis. In vitro MNA did not modify platelet aggregation nor induce vasodilation.Conclusions and implications:MNA displayed a profile of anti‐thrombotic activity in vivo that surpasses that of closely related compounds. MNA inhibited platelet‐dependent thrombosis by a mechanism involving cyclooxygenase‐2 and prostacyclin. Our findings suggest that endogenous MNA, produced in the liver by nicotinamide N‐methyltransferase, could be an endogenous activator of prostacyclin production and thus may regulate thrombotic as well as inflammatory processes in the cardiovascular system.British Journal of Pharmacology (2007) 152, 230–239; doi:10.1038/sj.bjp.0707383
Involvement of the sigma1(σ1) receptor in the anti‐amnesic, but not antidepressant‐like, effects of the aminotetrahydrofuran derivative ANAVEX1‐41
Authors: Espallergues J , Lapalud P , Christopoulos A , Avlani V A , Sexton P M , Vamvakides A , Maurice T 
Published: July 2007

Background and purpose:Tetrahydro‐N, N‐dimethyl‐5, 5‐diphenyl‐3‐furanmethanamine hydrochloride (ANAVEX1‐41) is a potent muscarinic and sigma1(σ1) receptor ligand. Theσ1receptor modulates glutamatergic and cholinergic responses in the forebrain and selective agonists are potent anti‐amnesic and antidepressant drugs. We have here analysed theσ1component in the behavioural effects of ANAVEX1‐41.Experimental approach:Binding of ANAVEX1‐41 to muscarinic andσ1receptors were measured using cell membranes. Behavioural effects of ANAVEX1‐41 were tested in mice using memory (spontaneous alternation, passive avoidance, water‐maze) and antidepressant‐like activity (forced swimming) procedures.Key results:In vitro, ANAVEX1‐41 was a potent muscarinic (M1>M3, M4>M2with Kiranging from 18 to 114 nM) and selectiveσ1ligand (σ1, Ki=44 nM;σ2, Ki=4 μM). In mice, ANAVEX1‐41 failed to affect learning when injected alone (0.03–1 mg kg−1), but attenuated scopolamine‐induced amnesia with a bell‐shaped dose response (maximum at 0.1 mg kg−1). Theσ1antagonist BD1047 blocked the anti‐amnesic effect of ANAVEX1‐41 on both short‐ and long‐term memories. Pretreatment with aσ1receptor‐directed antisense oligodeoxynucleotide prevented effects of ANAVEX1‐41 only in the passive avoidance procedure, measuring long‐term memory. ANAVEX1‐41 reduced behavioural despair at 30 and 60 mg kg−1, without involving theσ1receptor, as it was not blocked by BD1047 or the antisense oligodeoxynucleotide.Conclusions and implications:ANAVEX1‐41 is a potent anti‐amnesic drug, acting through muscarinic andσ1receptors. The latter component may be involved in the enhancing effects of the drug on long‐term memory processes.British Journal of Pharmacology(2007)152, 267–279; doi:10.1038/sj.bjp.0707386
Imbalanced synthesis of cyclooxygenase‐derived thromboxane A2 and prostacyclin compromises vasomotor function of the thoracic aorta in Marfan syndrome
Authors: Chung A W Y , Yang H H C , van Breemen C 
Published: July 2007

Background and purpose:Thoracic aortic dissection is a life‐threatening complication of Marfan syndrome, a connective tissue disorder caused by mutations in the gene encoding fibrillin‐1. We have demonstrated that nitric oxide‐mediated endothelial‐dependent relaxation is impaired in the thoracic aorta in Marfan syndrome. In the present study, we determined whether the cyclooxygenase (COX)‐pathway is involved in the compromised aortic vasomotor function.Experimental approach:Thoracic aortae from mice at 3, 6 and 9 months of age, heterozygous for the Fbn1 allele encoding a cysteine substitution (Fbn1
C1039G/+, ‘Marfan’, n=35), were compared with those from age‐matched controls (n=35).Key results:Isometric force measurement revealed that preincubation with indomethacin, a non‐specific COX inhibitor, but not valeryl salicylate, a specific COX‐1 inhibitor, improved the phenylephrine‐induced contractions (at 6 months, EC50 and Emax were increased 4.5‐fold and by 45%, respectively) in Marfan aortae. Sensitivity to acetylcholine‐induced relaxation was improved 10‐fold. Blockade of the thromboxane‐endoperoxide receptor by SQ‐29548 did not affect phenylephrine‐mediated contractions in Marfan aortae, although they did respond to the thromboxane analogue, U46619. From 6 months on, phenylephrine‐induced secretion of prostacyclin and thromboxane A2 in Marfan aortae was 200% and 40%, respectively, of those in controls. Reduced COX‐1 expression was detected in Marfan aortae at 3 and 9 months, whilst COX‐2 expression was increased from 3 months on.Conclusions and implications:The compromised vasomotor function in Marfan thoracic aortae is associated with an imbalanced synthesis of thromboxane A2 and prostacyclin resulting from the differential protein expression of COX‐1 and COX‐2.British Journal of Pharmacology (2007) 152, 305–312; doi:10.1038/sj.bjp.0707391; published online 16 July 2007
Mechanisms of endothelin‐1‐induced decrease in contractility in adult mouse ventricular myocytes
Authors: Nishimaru K , Miura Y , Endoh M 
Published: July 2007

Background and purpose:The potent vasoconstrictor polypeptide endothelin‐1 (ET‐1) plays an important pathophysiological role in progression of cardiovascular diseases and elicits prominent effects on myocardial contractility. Although ET‐1 produces a positive inotropy in cardiac muscle of most mammalian species, it induces a sustained negative inotropy in mice. This study was performed to gain an insight into the cellular mechanisms underlying the negative inotropy in adult mouse ventricular myocytes.Experimental approach:Cell shortening and Ca2+ transients were simultaneously recorded from isolated mouse ventricular myocytes loaded with the Ca2+‐sensitive fluorescent dye indo‐1.Key results:ET‐1 decreased cell shortening in a concentration‐dependent manner (pD2 value of 10.1). The ET‐1‐induced decrease in cell shortening was associated with a decrease in Ca2+ transients. In addition, the Ca2+ transient/cell‐shortening relationship was shifted to the right by ET‐1, indicating decreased myofilament Ca2+ sensitivity. The instantaneous relationship of the rising phase of the Ca2+ transient and cell shortening was shifted to the right by ET‐1. Decreased Ca2+ transients and cell shortening induced by ET‐1 were markedly attenuated by the specific Na+/Ca2+ exchange inhibitor SEA0400.Conclusions and implications:ET‐1‐induced negative inotropy in mouse ventricular myocytes was mediated by decreased Ca2+ transients and myofilament Ca2+ sensitivity. These data are entirely consistent with the involvement of increased Ca2+ extrusion via the Na+/Ca2+ exchanger in the ET‐1‐mediated decrease in Ca2+ transients. Decreased Ca2+ sensitivity may be due to retardation of cell shortening in response to a rise in Ca2+ transients.British Journal of Pharmacology (2007) 152, 456–463; doi:10.1038/sj.bjp.0707392; published online 16 July 2007
Building a better aspirin: gaseous solutions to a century‐old problem
Authors: Wallace J L 
Published: July 2007

The gastrointestinal adverse effects of nonsteroidal anti‐inflammatory drugs (NSAIDs) have been recognized since shortly after the introduction of aspirin to the marketplace over a century ago. However, the underlying pathogenesis of NSAID‐induced gastropathy remains incompletely understood. Advances in understanding some of the factors that contribute to the mucosal injury have provided clues for the development of safer NSAIDs. The inhibitory effects of nitric oxide (NO) on NSAID‐induced leukocyte adherence were exploited in the development of NO‐releasing NSAIDs. As well as eliciting less gastrointestinal damage than conventional NSAIDs, these drugs do not elevate blood pressure and show anti‐inflammatory effects, additional to those of the parent drugs. Modification of other drugs in a similar manner (i.e., NO‐releasing derivatives) has similarly resulted in more effective drugs. More recently, hydrogen sulphide‐releasing derivatives of NSAIDs and of other drugs, have been developed, based on the observed ability of H2S to reduce inflammation and pain in experimental models. H2S‐releasing NSAIDs produce negligible gastric damage and exhibit enhanced anti‐inflammatory potency as compared to the parent drugs. The NO‐NSAIDs and H2S‐releasing NSAIDs represent examples of new anti‐inflammatory drugs with greatly reduced toxicity and improved therapeutic activity, both created through the concept of exploiting the beneficial effects of endogenous gaseous mediators.British Journal of Pharmacology(2007)152, 421–428; doi:10.1038/sj.bjp.0707396; published online 16 July 2007
Cannabinoids inhibit noradrenergic and purinergic sympathetic cotransmission in the rat isolated mesenteric arterial bed
Authors: Pakdeechote P , Dunn W R , Ralevic V 
Published: July 2007

Background and purpose:Noradrenaline and ATP are sympathetic co‐transmitters. In the rat perfused mesenteric bed cannabinoids have been shown to modify the overall response to sympathetic nerve stimulation. This study has assessed whether cannabinoid receptor activation modulates differentially the noradrenergic and purinergic components of sympathetic vasoconstriction.Experimental approach:Rat mesenteric beds were perfused with physiological salt solution and the effects of cannabinoids on responses to nerve stimulation, or exogenous noradrenaline orα,β‐methylene ATP (α,β‐meATP; P2X receptor agonist) were determined after raising tone with U46619. The effects of cannabinoids on the noradrenaline and ATP components of sympathetic neurotransmission were assessed using theα1‐adrenoceptor antagonist, prazosin, or after P2X receptor desensitization withα,β‐meATP.Key results:Anandamide, WIN 55,212‐2 and CP55,940 attenuated sympathetic neurogenic vasoconstrictor responses. The inhibitory actions of anandamide and WIN 55,212‐2 were blocked by LY320135, a CB1receptor antagonist, but not by SR144528, a CB2receptor antagonist. The inhibitory actions of CP55,940 were unaffected by LY320135 and SR144528. WIN 55,212‐3, the inactive S(−) enantiomer of WIN 55,212‐2, had no effect on sympathetic neurogenic responses. None of the cannabinoids affected contractile responses to exogenous noradrenaline orα,β‐meATP. Anandamide and WIN 55,212‐2 inhibited both the noradrenaline and ATP components of the sympathetic neurogenic contractile responses, with effects on the ATP component being most marked.Conclusions and implications:These results indicate that prejunctional CB1‐like receptors mediate the sympathoinhibitory action of anandamide and WIN 55,212‐2, but not CP55,940, in the rat mesenteric bed. Cannabinoids inhibit both the noradrenergic and purinergic components of sympathetic neurotransmission.British Journal of Pharmacology(2007)152, 725–733; doi:10.1038/sj.bjp.0707397; published online 16 July 2007
A potyvirus P1 protein interacts with the Rieske Fe/S protein of its host
Authors: SHI YUHONG , CHEN JIONG , HONG XUEYU , CHEN JIANPING , ADAMS MICHAEL J. 
Published: July 2007

ABSTRACTYeast two‐hybrid (Y2H) screens were used to test for interactions between the P1 protein ofSoybean mosaic virusPinellia isolate (SMV‐P) and a cDNA expression library of its host, the aroidPinellia ternata.Of the 13 independent interacting clones identified, ten were identical and had an open reading frame predicted to encode a 23.7‐kDa protein closely related to the cytochromeb6/fcomplex Rieske Fe/S genes of plants. The interaction between SMV‐P‐P1 and the mature Rieske Fe/S protein (without transit peptide) of the host was confirmed byin vitroco‐immunoprecipitation of the two proteins. Y2H assays using different parts of the two proteins showed that only the N‐terminal part (amino acids 1–82) of SMV‐P P1 was responsible for the interaction with the Rieske Fe/S protein and that amino acids 1–33 interacted only with the transit peptide, while amino acids 34–82 could interact with the entire Rieske Fe/S protein. SMV‐P P1 also interacted moderately with the Rieske Fe/S protein of its other hosts, soybean andZantedeschia aethiopica, but weakly with that of the non‐hostArabidopsis thaliana. The P1‐Rieske Fe/S protein interactions are likely to be involved in symptom development, and the very variable N‐terminus of P1 may play an important role in host adaptation.
Enhanced antitumour immunity by combined use of temozolomide and TAT‐survivin pulsed dendritic cells in a murine glioma
Authors: Kim Chang‐Hyun , Woo Sun‐Je , Park Jung‐Sun , Kim Hye‐Sung , Park Mi‐Young , Park Sung‐Dong , Hong Yong‐Kil , Kim Tai‐Gyu 
Published: July 2007

SummaryAlthough chemotherapy remains among the best treatment options for most cancers, adjuvant therapies such as dendritic cell (DC)‐based immunotherapy have been added to treatment protocols to destroy residual tumour cells. Combination treatment with low‐dose temozolomide (TMZ) chemotherapy followed by vaccination with TAT‐survivin‐pulsed DCs enhanced T‐cell responses specific for survivin and improved survival rate, as compared with DC alone or TMZ alone. Moreover, antigen‐specific immunity appears to be mediated by CD8+ T cells, as determined by in vitro T‐cell subset depletion. These studies demonstrated that a combination of low‐dose TMZ chemotherapy and TAT‐based DC immunotherapy may be a novel strategy for safe and effective treatment of malignant gliomas.
A qualitative investigation of the influence of time since graduation on English dentists’ approach to the care of young children
Authors: DAILEY YVONNE‐MARIE , MILSOM KEITH MARTIN , PILKINGTON LAURA , BLINKHORN ANTHONY STEPHENSON , THRELFALL ANTHONY GEORGE , TICKLE MARTIN 
Published: July 2007

Background.  In the UK, general dental practitioners (GDPs) provide the majority of dental care to young children. The approach to undergraduate teaching of paediatric dentistry varies across UK dental schools. There is no understanding of how undergraduate teaching influences practice in the first few years after qualification and how this influence behaves over time as dentists mature as clinicians.Objective.  The aim of this paper is to gain a deeper understanding of the influence of time since graduation on how GDPs manage the dental care of their child patients.Design.  A qualitative study, with three interviewers conducted 93 interviews with GDPs practising in the north‐west of England. Interviews were transcribed verbatim and content analysis was used with the purpose of identifying themes from the data.Results.  Findings showed that formal postgraduate education was not a great influence upon the GDPs’ approach to care over time. Change in approach was influenced by experiential learning over a GDP's career and external influences such as policy change, but this was not underpinned by any formal reflective practice.Conclusions.  Education is just one of many influences on clinical practice over the whole of a clinician's career. A gradual change in clinical practice is influenced by the personal experience of dentists treating children.
One‐week versus two‐week furazolidone‐based quadruple therapy as the first‐line treatment for Helicobacter pylori infection in Iran
Authors: Daghaghzadeh Hamed , Emami Mohammad Hasan , Karimi Somayeh , Raeisi Mostafa 
Published: July 2007

AbstractBackground and Aim:  Furazolidone‐based regimens for the eradication of Helicobacter pylori are low cost and effective although less tolerable. Our aim was to compare the efficacy and compliance of 1‐week furazolidone‐based quadruple therapy (furazolidone, amoxicillin, bismuth subcitrate, omeprazole; FABO) with 2‐week quadruple therapy using the same drugs.Methods:  One hundred and fifty‐six consecutive patients with H. pylori related diseases were enrolled in our study. The patients were randomized into two groups of FABO1 and FABO2 groups receiving, 1 or 2 weeks' quadruple H. pylori eradication therapies, respectively, as follows: furazolidone (200 mg twice daily), amoxicillin (1 g twice daily), bismuth (240 mg twice daily) and omeprazole (20 mg twice daily). The χ2 test was used to compare the efficacy of the therapies.Results:  The per‐protocol eradication rate in FABO1 and FABO2 groups were 56/66 (84.8%) and 57/69 (82.6%), respectively. The intention‐to‐treat eradication rate was 56/78 (71.8%) in FABO1 group and 57/78 (73.1%) in FABO2 group. There was not any significant statistical difference between two groups. A significant decrease in compliance in FABO2 group was seen.Conclusion:  This is an encouraging report showing a therapy with possible success in decreasing the duration of H. pylori infection as well as reaching the eradication rate of 80%.