bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimony‐induced cardiomyopathy in guinea‐pig and protection by L‐carnitine
Authors: Alvarez Marco , Malécot Claire O , Gannier François , Lignon Jacques M 
Published: December 2004

Antimony (Sb) is the mainstay for the treatment of Leishmaniasis. It has serious, often lethal, cardiovascular side effects. The objective of this study was to examine the effects of Sb treatment upon the electrocardiogram (ECG), myocyte contractility (assessed by monitoring sarcomere length during field stimulation), whole‐cell action potential (AP) and calcium current (ICa) of the guinea‐pig and to evaluate L‐carnitine as a cardioprotective agent.
Guinea‐pigs received daily injections of either saline, Sb(V), Sb(III), L‐carnitine or L‐carnitine with Sb(III). Eight lead ECGs were recorded under halothane anaesthesia every 4 days. At the end of each treatment regime, animals were killed and ventricular myocytes were enzymatically isolated.
Treatment with Sb(V) for 26 days prolonged the QT interval of the ECG. Treatment with Sb(III) was lethal within 2 days for ∼50% of the animals. The survivors showed ECG alterations similar to those described in man: T wave flattening and/or inversion, depression of the ST segment, and elongation of RR and QT intervals. Their ventricular myocytes showed impaired contraction responses to changes in stimulus frequency, elongated AP and reduced ICa.
Combined treatment with L‐carnitine and Sb(III) delayed mortality. Prior treatment with L‐carnitine followed by combined treatment with L‐carnitine and Sb(III) reduced mortality to <10% over 12 days and these animals showed normal ECG. Their myocytes showed normal contractility and AP.
It is concluded that L‐carnitine has a preventive cardioprotective role against antimony‐induced cardiomyopathy. The mechanism of action of L‐carnitine may be to counter oxidative stress caused by Sb(III).

British Journal of Pharmacology (2005) 144, 17–27. doi:10.1038/sj.bjp.0706030
Prevention of progressive joint destruction in collagen‐induced arthritis in rats by a novel matrix metalloproteinase inhibitor, FR255031
Authors: Ishikawa Takeshi , Nishigaki Fusako , Miyata Susumu , Hirayama Yoshitaka , Minoura Kyoko , Imanishi Junko , Neya Masahiro , Mizutani Tsuyoshi , Imamura Yoshimasa , Naritomi Yoichi , Murai Hidetsugu , Ohkubo Yoshitaka , Kagayama Akira , Mutoh Seitaro 
Published: December 2004

FR255031 (2‐[(7S)‐7‐[5‐(4‐ethylphenyl)‐2‐thienyl]‐1,1‐dioxido‐4‐(2‐pyridinylcarbonyl)hexahydro‐1,4‐thiazepin‐7‐yl]‐N‐hydroxyacetamide) is a novel synthetic matrix metalloproteinase (MMP) inhibitor that inhibits human collagenases (MMP‐1, MMP‐8 and MMP‐13), gelatinases (MMP‐2 and MMP‐9) and membrane type 1 MMP (MT1‐MMP/MMP‐14). FR255031 also inhibits rat collagenase and gelatinase. We studied the effect of FR255031 and Trocade, an inhibitor of collagenase and MMP‐14, on a rat collagen‐induced arthritis (CIA) model.Rat CIA was induced by intradermal injection of type II collagen (IIC) and oral administration of FR255031 or Trocade was performed for 28 days. Body weight loss, hind paw swelling, elevation of serum anti‐IIC antibody, and histological and radiographic scores were evaluated.FR255031 markedly inhibited cartilage degradation in a dose‐dependent manner in the CIA model, but Trocade failed to prevent the degradation.FR255031 at a dose of 100 mg kg−1also had statistically significant effects on bone destruction and pannus formation and on the recovery of body weight loss on day 28.These results indicate that FR255031 is effective for rat CIA, especially on joint cartilage destruction. These data suggest that as well as collagenases or MT‐MMP, gelatinases are also involved in joint destruction in arthritis.British Journal of Pharmacology(2005)144, 133–143. doi:10.1038/sj.bjp.0706054
Positron emission tomography using 18F‐labelled endothelin‐1 reveals prevention of binding to cardiac receptors owing to tissue‐specific clearance by ETB receptors in vivo
Authors: Johnström Peter , Fryer Tim D , Richards Hugh K , Harris Neil G , Barret Olivier , Clark John C , Pickard John D , Davenport Anthony P 
Published: December 2004

Our aim was to synthesise an 18F analogue of endothelin‐1 (ET‐1), to dynamically image ET receptors in vivo by positron emission tomography (PET) and to elucidate the function of the ETB subtype as a clearing receptor in organs expressing high densities including kidney and lung.
[18F]‐ET‐1 was characterised in vitro and bound with a single subnanomolar affinity (KD=0.43±0.05 nM, Bmax=27.8±2.1 fmol mg−1 protein) to human left ventricle (n=4).
The in vivo distribution of [18F]‐ET‐1 in anaesthetised rats was measured using a dedicated small animal PET scanner (microPET) and ex vivo analysis.
Dynamic PET data demonstrated that high levels of radioligand accumulated rapidly in the lung, kidney and liver, consistent with receptor binding. The in vivo distribution correlated with the anatomical localisation of receptors detected in vitro using [125I]‐ET‐1. However, the receptor density visualised in the heart was unexpectedly low compared with that predicted from the in vitro measurements.
[18F]‐ET‐1 binding in lungs could not be displaced by the ETB selective antagonist BQ788, in agreement with the proposed internalisation of ET‐1 by ETB receptors. In contrast, infusion of BQ788 prior to injecting [18F]‐ET‐1 significantly reduce the amount of radioligand visualised in the ETB rich lung and kidney by 85% (P<0.05, n=3) and 55% (P<0.05, n=3), respectively.
Under conditions of ETB receptor blockade, the heart could be visualised by microPET imaging.
These results suggest that clearance by ETB receptors in the lung and kidney prevents binding of ET‐1 to receptors in the heart.

British Journal of Pharmacology (2005) 144, 115–122. doi:10.1038/sj.bjp.0706064
Farnesol is glucuronidated in human liver, kidney and intestine in vitro, and is a novel substrate for UGT2B7 and UGT1A1
Authors: STAINES Adam G. , SINDELAR Pavel , COUGHTRIE Michael W. H. , BURCHELL Brian 
Published: December 2004

Farnesol is an isoprenoid found in many aromatic plants and is also produced in humans, where it acts on numerous nuclear receptors and has received considerable attention due to its apparent anticancer properties. Although farnesol has been studied for over 30 years, its metabolism has not been well characterized. Recently, farnesol was shown to be metabolized by cytochromes P450 in rabbit; however, neither farnesol hydroxylation nor glucuronidation in humans have been reported to date. In the present paper, we show for the first time that farnesol is metabolized to farnesyl glucuronide, hydroxyfarnesol and hydroxyfarnesyl glucuronide by human tissue microsomes, and we identify the specific human UGTs (uridine diphosphoglucuronosyltransferases) involved. Farnesol metabolism was examined by a sensitive LC (liquid chromatography)–MS/MS method. Results indicate that farnesol is a good substrate for glucuronidation in human liver, kidney and intestine microsomes (values in nmol/min per mg). Initial analysis using expressed human UGTs indicated that UGTs 1A1 and 2B7 were primarily responsible for glucuronidation in vitro, with significantly lower activity for all the other UGTs tested (UGTs 1A3, 1A4, 1A6, 1A9 and 2B4). Kinetic analysis and inhibition experiments indicate that, in liver microsomes, UGT1A1 is primarily responsible for farnesol glucuronidation; however, in intestine microsomes, UGT2B7 is probably the major isoform involved, with a very-low-micromolar Km. We also show the first direct evidence that farnesol can be metabolized to hydroxyfarnesol by human liver microsomes and that hydroxyfarnesol is metabolized further to hydroxyfarnesyl glucuronide. Thus glucuronidation may modulate the physiological and/or pharmacological properties of this potent signalling molecule.
Expression and refolding of Omp38 from Burkholderia pseudomallei and Burkholderia thailandensis, and its function as a diffusion porin
Authors: SIRITAPETAWEE Jaruwan , PRINZ Heino , KRITTANAI Chartchai , SUGINTA Wipa 
Published: December 2004

In the present paper, we describe cloning and expression of two outer membrane proteins, BpsOmp38 (from Burkholderia pseudomallei) and BthOmp38 (from Burkholderia thailandensis) lacking signal peptide sequences, using the pET23d(+) expression vector and Escherichia coli host strain Origami(DE3). The 38 kDa proteins, expressed as insoluble inclusion bodies, were purified, solubilized in 8 M urea, and then subjected to refolding experiments. As seen on SDS/PAGE, the 38 kDa band completely migrated to ∼110 kDa when the purified monomeric proteins were refolded in a buffer system containing 10% (w/v) Zwittergent® 3-14, together with a subsequent heating to 95 °C for 5 min. CD spectroscopy revealed that the 110 kDa proteins contained a predominant β-sheet structure, which corresponded completely to the structure of the Omp38 proteins isolated from B. pseudomallei and B. thailandensis. Immunoblot analysis using anti-BpsOmp38 polyclonal antibodies and peptide mass analysis by MALDI–TOF (matrix-assisted laser-desorption ionization–time-of-flight) MS confirmed that the expressed proteins were BpsOmp38 and BthOmp38. The anti-BpsOmp38 antibodies considerably exhibited the inhibitory effects on the permeation of small sugars through the Omp38-reconstituted liposomes. A linear relation between relative permeability rates and Mr of neutral sugars and charged antibiotics suggested strongly that the in vitro re-assembled Omp38 functioned fully as a diffusion porin.
Rights of Foreign Workers and the Politics of Migration in South‐East and East Asia
Authors: Piper Nicola 
Published: December 2004

AbstractThe issue of cross‐border migration in South‐East and East Asia is linked to the integration of regional, if not global, labour markets. The types of labour that are currently in demand have changed substantially since the 1990s in terms of (1) overall magnitude, (2) gender composition, and (3) increased diversification. This paper, however, focuses upon those workers classified as unskilled as they constitute numerically the largest and most vulnerable group. The challenges to provide adequate protection from, and prevention of, exploitative and abusive practices that seriously minimize the socio‐economic benefits for these workers are linked to migration policies and the issue of rights in the origin and destination countries.This paper's objective is to provide a broad outline of the emerging trends and issues revolving around contemporary cross‐border labour migration and the politics of migrants' rights in South‐East and East Asia, illustrated by the difficulties experienced with the ratification of the 1990 United Nations Convention on the Rights of All Migrants and their Families (ICMR). The data this paper is based upon were collected for a report commissioned by the United Nations Educational, Scientific and Cultural Organization (UNESCO) with fieldwork carried out in seven countries located in the Asia Pacific region.It is argued that ratification of the ICMR is obstructed by politics and by a lack of political will. A rights‐based approach to the protection of migrant labour is thus related to a number of macro and micro level issues, revolving around development and practices of “good governance” in addition to interstate relations. This means that the promotion of migrants' rights requires a holistic approach addressing national and transnational issues in an era of increasing mobility across borders.
The sentimental city: the lost urbanism of Pierre Mac Orlan and Guy Debord
Authors: Merrifield Andy 
Published: December 2004

Behind a high stonewall surrounding a rural farmhouse in Auvergne, Guy Debord, the ex‐Situationist theorist and activist, retreated. The grungy, cheap‐thrill Parisian urbanism of his youth was no more. Paris had died in his arms of a fatal illness that has seen off other great cities. Economic forces and planning initiatives had assassinated his rebel underworld, and culprits are still at large, still awaiting trial in the people's court. This essay embraces Debord the other side of the wall, dialoging with Pierre Mac Orlan, one of his favorite novelists. In so doing, we enter the phantasmal zone of the sentimental city, the city both real and make‐believe, defunct and yet‐to‐be. Mac Orlan's ideas about passive and active adventuring are explored here, to unlock the Pandora's box of Debord's urbanism. The essay approaches the capitalist city with a poetic gloss and reveals a realm richer and deeper than most social scientific urban research can grasp. Alongside Mac Orlan, Debord retraces his steps through urban ruins, and recaptures an everyday melancholy of backstreets and damaged people, of twilight nooks and crannies and shadowy bars. In Debord's sentimental city, it isn't so much the past that one regrets as the future.Derrière un haut mur de pierre entourant une ferme d'Auvergne, s'est retiré Guy Debord, l'ancien théoricien et militant situationniste. L'urbanisme parisien minable et décadent de sa jeunesse n'existait plus. Paris était mort dans ses bras d'une maladie désastreuse qui a emporté d'autres grandes villes. Forces économiques et initiatives d'aménagement ont assassiné son milieu rebelle et les coupables courent encore, dans l'attente d'un procès populaire. Cet essai voit Debord de l'autre côté du mur en train de dialoguer avec Pierre Mac Orlan, l'un de ses écrivains favoris. Ainsi, nous entrons dans l'illusion de la ville sentimentale, ville à la fois réelle et imaginaire, défunte et survivante. Les idées de Mac Orlan sur l'aventurier actif et passif y sont examinées afin d'ouvrir la boîte de Pandore de l'urbanisme selon Debord. L'approche de la ville capitaliste revêt un vernis poétique, révélant un univers plus riche et plus profond que ce qui peut être saisi par la plupart des recherches urbaines en sciences sociales. Aux côtés de Mac Orlan, Debord revient sur ses pas, traversant des ruines urbaines, retrouvant une mélancolie au quotidien des bas‐quartiers et d'une pègre abîmée, des coins et recoins obscurs et des bars mal éclairés. Dans la ville sentimentale de Debord, ce n'est pas tant le passé que l'on regrette, mais plutôt l'avenir.
Increased interferon gamma production by peripheral blood mononuclear cells in response to stimulation of overexpressed disease‐specific 9‐O‐acetylated sialoglycoconjugates in children suffering from acute lymphoblastic leukaemia
Authors: Ghosh Shyamasree , Bandyopadhyay Suman , Pal Santanu , Das Benubrata , Bhattacharya Dilip K. , Mandal Chitra 
Published: December 2004

SummaryDisease‐specific over‐expression of 9‐O‐acetylated sialoglycoconjugates (9‐O‐AcSGs) on peripheral blood mononuclear cells (PBMC) of children with acute lymphoblastic leukaemia (ALL, PBMCALL) has been demonstrated using a lectin, Achatinin‐H, with specificity towards 9‐O‐AcSAα2‐6GalNAc. This study investigated the contributory role of 9‐O‐AcSGs induced on PBMCALL. Stimulation of PBMCALL with Achatinin‐H through 9‐O‐AcSGs led to a lymphoproliferative response with a significantly increased interferon‐γ (IFN‐γ) production when compared with unstimulated cells as demonstrated by enzyme‐linked immunosorbent assay and mRNA expression. Under identical conditions, PBMCALL ablated of O‐acetylations did not respond to such stimulation. In summary, it may be concluded that stimulation of over‐expressed 9‐O‐AcSGs regulate signalling for proliferation, leading to the release of IFN‐γ. Controlled expression of these molecules may be exploited as potential targets for therapy, promising beneficial effects to children with ALL.
Advanced glycation end‐products in sickle cell anaemia
Authors: Somjee Saika S. , Warrier Rajasekharan P. , Thomson Jessica L. , Ory‐Ascani Jeannine , Hempe James M. 
Published: December 2004

SummaryTissue accumulation of advanced glycation end‐products (AGEs) has been implicated in the oxidant‐induced vascular pathology of diabetes and other diseases. Because homozygous sickle cell anaemia (SCA) is a state of oxidative stress, we tested the hypothesis that circulating AGE levels are elevated in SCA. Blood was obtained from age‐ and race‐matched children classified as either non‐sickle cell controls, SCA without vaso‐occlusive crisis (SCA − VOC), or SCA with vaso‐occlusive crisis (SCA + VOC). Plasma and red blood cell (RBC) AGE levels were measured by immunoassay. RBC levels of reduced (GSH) and oxidized (GSSG) glutathione were measured by capillary electrophoresis as an indicator of endogenous antioxidant status. The results showed that plasma AGE levels and the rate of RBC AGE accumulation were significantly higher in patients with SCA compared with controls. GSH was not different between groups but was significantly inversely correlated with plasma AGEs in both controls and patients with SCA. GSSG was significantly lower and GSH/GSSG higher in SCA + VOC patients, suggesting that GSH/GSSG might be an objective indicator of acute VOC or a risk factor for VOC. We conclude that circulating AGE levels are strongly influenced by endogenous antioxidant status and may play a role in the vascular pathology of SCA.
Factor‐V expression in platelets from human megakaryocytic culture
Authors: Giampaolo Adele , Vulcano Francesca , Macioce Giampiero , Mattia Gianfranco , Barca Alessandra , Milazzo Luisa , Ciccarelli Carmela , Hassan Hamisa J. 
Published: December 2004

SummaryThe origin of platelet‐factor‐V has long been discussed. To elucidate whether and when human platelet‐factor‐V is synthesized by megakaryocytes, we utilized in vitro‐generated megakaryocytes capable of producing platelets. Factor‐V gene was silent in purified progenitors and megakaryocytic precursors but was expressed in late culture phase and maintained also in platelets. Similarly, factor‐V protein was expressed in mature proplatelet‐bearing megakaryocytes (immunofluorescence analysis); it was also detectable in cultured megakaryocytes and platelets (Western blotting) and within permeabilized cultured platelets (flow cytometry). The absence of other cells in our culture system indicates conclusively that human megakaryocytes synthesize factor‐V.
Uterine tumours are a phenotypic manifestation of the hyperparathyroidism‐jaw tumour syndrome
Authors: BRADLEY K. J. , HOBBS M. R. , BULEY I. D. , CARPTEN J. D. , CAVACO B. M. , FARES J. E. , LAIDLER P. , MANEK S. , ROBBINS C. M. , SALTI I. S. , THOMPSON N. W. , JACKSON C. E. , THAKKER R. V. 
Published: December 2004

Abstract.The hyperparathyroidism‐jaw tumour (HPT‐JT) syndrome is an autosomal dominant disorder characterized by parathyroid tumours, which are frequently carcinomas, and ossifying jaw fibromas. In addition, some patients may develop renal tumours and cysts. The gene causing HPT‐JT, which is referred to as HRPT2 and is located on chromosome 1q31.2, encodes a 531 amino acid protein called PARAFIBROMIN. To date 42 mutations, of which 22 are germline, have been reported and 97% of these are inactivating and consistent with a tumour suppressor role for HRPT2. We have investigated another four HPT‐JT families for germline mutations, searched for additional clinical phenotypes, and examined for a genotype–phenotype correlation. Mutations were found in two families. One family had a novel deletional‐insertion at codon 669, and the other had a 2 bp insertion at codon 679, which has been reported in four other unrelated patients. These five unrelated patients and their families with the same mutation were not found to develop the same tumours, thereby indicating an absence of a genotype–phenotype correlation. An analysis of 33 HPT‐JT kindreds revealed that affected women in 13 HPT‐JT families suffered from menorrhagia in their second to fourth decades. This often required hysterectomy, which revealed the presence of uterine tumours. This resulted in a significantly reduced maternal transmission of the disease. Thus, the results of our analysis expand the spectrum of HPT‐JT‐associated tumours to include uterine tumours, and these may account for the decreased reproductive fitness in females from HPT‐JT families.
Age‐related increase of pulse pressure and plasminogen activator inhibitor‐1 I/D gene polymorphism in essential hypertension
Authors: MOURAD J.‐J. , DU CAILAR G. , NAZAL E.‐M. , SAFAR M. E. , MIMRAN A. 
Published: December 2004

Abstract.Background.  Pulse pressure (PP), a marker of cyclic strain on the arterial wall, is a significant predictor of cardiovascular (CV) risk, particularly regarding the incidence of coronary arterial stenosis. Genes related to haemostatic and/or fibrinolytic factors are consistently influenced in vitro by mechanical strain.Objective.  The goal of the present study was to determine, in the three genotypes of the plasminogen activator inhibitor (PAI)‐1 gene polymorphism, the gender‐adjusted difference in the relationships between age and PP in subjects with never treated essential hypertension.Results.  In the studied population, the genotype deletion (D)/D at position −675 of the PAI‐1 insertion (I)/D gene polymorphism was associated with a significant increase in the adjusted slope of the curve relating age to PP by comparison with the two other genotypes. No comparable difference in age‐related changes in systolic, diastolic or mean blood pressure was found.Conclusion.  In subjects with essential hypertension, the PAI‐1 I/D gene polymorphism modulates the age‐mediated increase of PP, suggesting new insights on the complex interactions between genes, mechanical factors and CV risk.
Abnormal circulating levels of metalloprotease 9 and its tissue inhibitor 1 in angiographically proven peripheral arterial disease: relationship to disease severity
Authors: TAYEBJEE M. H. , TAN K. T. , MACFADYEN R. J. , LIP G. Y. H. 
Published: December 2004

Abstract.Background.  Peripheral arterial disease (PAD) is associated with adaptive changes in the vascular and muscle extracellular matrix (ECM) in response to reduced blood flow. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), are key modulators of ECM turnover. We hypothesized that patients with intermittent claudication (with low ankle‐brachial blood pressure index, <0.8), and critical ischaemia would have raised circulating levels of MMP‐9, TIMP‐1 and TIMP‐2 compared with healthy controls, reflecting an increase in proteolytic activity which may be related to ECM turnover in PAD.Methods.  We studied 36 patients (23 males; 65 ± 9 years) with intermittent claudication and 43 (25 males; 68 ± 12) patients with critical ischaemia. All patients had angiographic evidence confirming significant PAD.Results.  Circulating levels of MMP‐9 and TIMP‐1 were higher (both P < 0.0001) in the PAD patient groups compared with the controls. Patients with critical ischaemia had MMP‐9 and TIMP‐1 levels that were significantly higher than those with intermittent claudication. There were no differences in circulating TIMP‐2 levels between patients and controls. There was a modest positive correlation between the white cell count (WCC) and MMP‐9, both patients with intermittent claudication (Spearman, r = 0.398, P = 0.016) and critical ischaemia (r = 0.378, P = 0.014).Conclusion.  We demonstrate higher levels of circulating MMP‐9 and TIMP‐1 in patients with intermittent claudication and critical ischaemia. Circulating concentrations of both markers can be related to disease severity, being higher in critical ischaemia compared with levels in intermittent claudication.