bluuebunny/crossref_metadata_2025_split huggingface dataset:
The negative inotropic action of canrenone is mediated by L‐type calcium current blockade and reduced intracellular calcium transients
Authors: Costa AR , Torres LB , Medei E , Ricardo RA , França JP , Smaili S , Nascimento JHM , Oshiro MEM , Bassani JWM , Ferreira AT , Tucci PJF 
Published: August 2009

Background and purpose: Adding spironolactone to standard therapy in heart failure reduces morbidity and mortality, but the underlying mechanisms are not fully understood. We analysed the effect of canrenone, the major active metabolite of spironolactone, on myocardial contractility and intracellular calcium homeostasis.Experimental approach: Left ventricular papillary muscles and cardiomyocytes were isolated from male Wistar rats. Contractility of papillary muscles was assessed with force transducers, Ca2+transients by fluorescence and Ca2+fluxes by electrophysiological techniques.Key results: Canrenone (300–600 µmol·L−1) reduced developed tension, maximum rate of tension increase and maximum rate of tension decay of papillary muscles. In cardiomyocytes, canrenone (50 µmol·L−1) reduced cell shortening and L‐type Ca2+channel current, whereas steady‐state activation and inactivation, and reactivation curves were unchanged. Canrenone also decreased the Ca2+content of the sarcoplasmic reticulum, intracellular Ca2+transient amplitude and intracellular diastolic Ca2+concentration. However, the time course of [Ca2+]idecline during transients evoked by caffeine was not affected by canrenone.Conclusion and implications: Canrenone reduced L‐type Ca2+channel current, amplitude of intracellular Ca2+transients and Ca2+content of sarcoplasmic reticulum in cardiomyocytes. These changes are likely to underlie the negative inotropic effect of canrenone.
Dog left ventricular midmyocardial myocytes for assessment of drug‐induced delayed repolarization: short‐term variability and proarrhythmic potential
Authors: Abi‐Gerges Najah , Valentin Jean‐Pierre , Pollard Chris E 
Published: August 2009

Background and purpose: Evaluation of the potential for delayed ventricular repolarization and proarrhythmia by new drugs is essential. We investigated if dog left ventricular midmyocardial myocytes (LVMMs) that can be used as a preclinical model to assess drug effects on action potential duration (APD) and whether in these cells, short‐term variability (STV) or triangulation could predict proarrhythmic potential.Experimental approach: Beagle LVMMs and Purkinje fibres (PFs) were used to record APs. Effects of six reference drugs were assessed on APD at 50% (APD50) and 90% (APD90) of repolarization, STV(APD), triangulation (ratio APD90/APD50) and incidence of early afterdepolarizations (EADs) at 1 and 0.5 Hz.Key results: LVMMs provided stable recordings of AP, which were not affected by four sequential additions of dimethyl sulphoxide. Effects of dofetilide, d‐sotalol, cisapride, pinacidil and diltiazem, but not of terfenadine, on APD in LVMMs were found to be comparable with those recorded in PFs. LVMMs, but not PFs, exhibited a proarrhythmic response toIKrblockers. Incidence of EADs was not related to differences in AP prolongation or triangulation, but corresponded to beat‐to‐beat variability of repolarization, here quantified as STV of APD.Conclusions and implications: LVMMs provide a suitable preclinical model to assess the effects of new drugs on APD and also yield additional information about putative indicators of proarrhythmia that add value to an integrated QT/TdP risk assessment. Our findings support the concept that increased STV(APD) may predict drug‐induced proarrhythmia.This article is part of a themed section on QT safety. To view this issue visithttp://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010
Metabolic characteristics of imatinib resistance in chronic myeloid leukaemia cells
Authors: Klawitter Jelena , Kominsky Douglas J , Brown Jaimi L , Klawitter Jost , Christians Uwe , Leibfritz Dieter , Melo Junia V , Eckhardt S Gail , Serkova Natalie J 
Published: August 2009

Background and purpose: Early detection of resistance development is crucial for imatinib‐based treatment in chronic myeloid leukaemia (CML) patients. We aimed to distinguish metabolic markers of cell resistance to imatinib.Experimental approach: Two human imatinib‐sensitive CML cell lines: LAMA84‐s and K562‐s, and their resistant counterparts: LAMA84‐r and K562‐r (both resistant to 1 µM imatinib), and K562‐R (5 µM) were analysed by nuclear magnetic resonance spectroscopy to assess global metabolic profiling, including energy state, glucose and phospholipid metabolism.Key results: We found, by Western blotting and flow cytometry, that the levels of Bcr‐Abl tyrosine kinase and multi‐drug resistance p‐glycoprotein were inconsistent among resistant clones. On the other hand, phospholipid metabolism and lactate production were highly predictive for cell response to imatinib. As previously reported, sensitive cells showed significantly decreased glycolytic activity (lactate) and phospholipid synthesis (phosphocholine) as well as increased phospholipid catabolism (glycerophosphocholine) after 24 h of 1 µM imatinib treatment, which correlated with inhibition of cell proliferation and induction of apoptosis. In contrast to their sensitive counterparts, the K562‐r, K562‐R and LAMA84‐r maintained increased phospholipid synthesis and glycolytic lactate production in the presence of 1 µM (K562‐r and LAMA84‐r) and 5 µM (K562‐R) imatinib.Conclusions and implications: Specific metabolic markers for early detection of imatinib resistance, including increased glycolytic activity and phospholipid turnover, can be identified in resistant clones. Once validated in human isolated leukocytes, they may be used to monitor the responsiveness of CML patients to treatment.
Mechanical Dissociation of Swine Liver to Produce Organoid Units for Tissue Engineering and In Vitro Disease Modeling
Authors: Irani Katayun , Pomerantseva Irina , Hart Alison R. , Sundback Cathryn A. , Neville Craig M. , Vacanti Joseph P. 
Published: August 2009

AbstractThe complex intricate architecture of the liver is crucial to hepatic function. Standard protocols used for enzymatic digestion to isolate hepatocytes destroy tissue structure and result in significant loss of synthetic, metabolic, and detoxification processes. We describe a process using mechanical dissociation to generate hepatic organoids with preserved intrinsic tissue architecture from swine liver. Oxygen‐supplemented perfusion culture better preserved organoid viability, morphology, serum protein synthesis, and urea production, compared with standard and oxygen‐supplemented static culture. Hepatic organoids offer an alternative source for hepatic assist devices, engineered liver, disease modeling, and xenobiotic testing.
Scaffold Modeling Application in the Repair of Skull Defects
Authors: Wan Weibing , Shi Pengfei 
Published: August 2009

AbstractThe repair of large segmental bone defects caused by trauma, inflammation, and surgery on tumors pose a major clinical challenge. Tissue‐engineered bone is emerging as a good choice for prefabricating cellular scaffold, and computer‐aided technologies and medical imaging have created new possibilities in biomedical engineering. An accurate and efficient construction of anatomic models is critical to the application of these computational methods. Such models must be validated prior to application. In this article, we explore the potential of combining these techniques to scaffold and repair a pediatric skull. Working under the hypothesis that the autogenously cultivated osteoblasts can be grown on individualized scaffolds to improve bone regeneration in skull defects, we focus our study on potential problems concerning the segmentation, reconstruction, and mesh simplification for a pediatric skull. We also propose a new framework to improve the accuracy of the model entity from image segmentation to mesh simplification.
What's new in Guillain‐Barré syndrome in 2007–2008?*
Authors: Van Doorn Pieter A. 
Published: August 2009

AbstractThe years 2007 and early 2008 have been an exciting time for Guillain‐Barré syndrome (GBS) research. Epidemiological studies have shown that the incidence of GBS remains stable at about 2/100,000 per year but that there have been changes in hospitalization use, likely due to the widespread availability of IVIg. Research into mechanisms has shown the importance of single amino acids in Campylobacter jejuni and the importance of ganglioside conformation. In a murine model of anti‐ganglioside antibody‐mediated neuropathy, Eculizumab was effective in reversing clinical disease and preventing pathology. This suggests trials of Eculizumab in GBS should be considered. Unfortunately, there are no new randomized controlled trials in GBS to report although the unmet need is great.
Schwann cells express the macrophage mannose receptor and MHC class II. Do they have a role in antigen presentation?
Authors: Baetas‐da‐Cruz Wagner , Alves Lucineia , Pessolani Maria Cristina V. , Barbosa Helene S. , Régnier‐Vigouroux Anne , Corte‐Real Suzana , Cavalcante Leny A. 
Published: August 2009

AbstractThe mannose receptor (MR) is a transmembrane glycoprotein, postulated to be a link between innate and adaptive immunity. MR is expressed in several cell types but no information is available on that for Schwann cells (SC). We show that rodent SC in primary cultures take up the MR ligand mannosyl/bovine serum albumin‐fluorescein isothiocyanate (man/BSA‐FITC) in a highly specific manner and bind an antibody against the C‐terminus of the murine macrophage MR (anti‐cMR). After incubation with man/BSA‐FITC, flow cytometry demonstrates 90% positive SC, a dose‐dependent increase in tagged cellular components and near total inhibition of the neoglycoprotein uptake by d‐mannose or by the mannosylated protein horseradish peroxidase (HRP). Western blot for MR shows that SC share a unique protein of about 180 kDa with peritoneal resident macrophages. Treatment of cultured SC with interferon‐γ (IFN‐γ) or dexamethasone (DM) followed by the addition of man/BSA‐FITC and analysis by flow cytometry shows down‐ or upregulation, respectively, of man/BSA‐FITC uptake. Our results show that SC express the MR in a prospectively functional state and suggest an antigen‐presenting function of SC, compatible with a role in infectious/inflammatory states of the peripheral nervous system.
Subcutaneous immunoglobulin therapy for multifocal motor neuropathy
Authors: Eftimov Filip , Vermeulen Marinus , De Haan Rob J. , Van Den Berg Leonard H. , Van Schaik Ivo N. 
Published: August 2009

AbstractThe objective of this study was to investigate whether subcutaneous immunoglobulin (SCIg) treatment is feasible and safe in maintaining muscle strength of patients with multifocal motor neuropathy (MMN). Patients fulfilling the EFNS/PNS criteria for definite MMN treated with intravenous immunoglobulin (IVIg) were switched to weekly SCIg in a single‐center, open‐label pilot intervention study. The first group of patients started with a SCIg dose equivalent to 50% of the IVIg maintenance dose. In case of deterioration, patients received a loading dose of IVIg and doubling of SCIg dose. The second group started with a dose equivalent to the IVIg maintenance dose. Primary outcome was the Medical Research Council (MRC) sum score from 10 muscle groups. Secondary outcomes were grip and pinch strength, dexterity, disability, quality of life, adverse events, and serum immunoglobulin concentrations. Ten patients were included, five in both groups. In the first group, one patient withdrew informed consent due to local adverse events, four deteriorated. In the second group, four out of five patients maintained muscle strength with SCIg during the 6 months follow‐up. Local adverse events were frequent, especially during first weeks of treatment, but generally well tolerated. Seven mild systemic adverse events were reported, all but one in the first week of treatment. In some, but not all MMN patients in this study, SCIg therapy was feasible and safe and maintained strength as well as IVIg. SCIg may be a viable alternative maintenance therapy in some patients with MMN currently receiving IVIg.
Defective Fas‐mediated T‐cell apoptosis predicts acute onset CIDP
Authors: Comi Cristoforo , Osio Maurizio , Ferretti Massimo , Mesturini Riccardo , Cappellano Giuseppe , Chiocchetti Annalisa , Carecchio Miryam , Nascimbene Caterina , Varrasi Claudia , Cantello Roberto , Mariani Claudio , Monaco Francesco , Dianzani Umberto 
Published: August 2009

AbstractGuillain‐Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune‐mediated neuropathies. GBS is characterized by acute onset and subsequent remission of symptoms, whereas CIDP displays slow progression over at least 2 months. However, a small proportion of CIDP patients display acute onset CIDP (a‐CIDP) resembling that of GBS. The Fas receptor is involved in shutting off the immune response and its defective function predisposes to auto‐immune diseases. In CIDP patients, Fas function is lower than in GBS patients and healthy controls. This study is aimed at assessing whether evaluation of T‐cell Fas function helps in early discrimination between GBS and a‐CIDP. Fas function was evaluated in patients with acute onset polyneuropathy: 55 retrospective patients analyzed after development of GBS or a‐CIDP before year 2005; 50 prospective patients analyzed at onset after year 2005 and followed up for development of GBS or a‐CIDP. In both groups, a‐CIDP patients displayed defective Fas function, whereas GBS patients displayed normal function. These findings suggest that the evaluation of Fas function in acute onset polyneuropathy helps in early prediction of long‐term outcome.
pSTAT1, pSTAT3, and T‐bet as markers of disease activity in chronic inflammatory demyelinating polyradiculoneuropathy
Authors: Madia Francesca , Frisullo Giovanni , Nociti Viviana , Conte Amelia , Luigetti Marco , Grande Alessandra Del , Patanella Agata Katia , Iorio Raffaele , Tonali Pietro Attilio , Batocchi Anna Paola , Sabatelli Mario 
Published: August 2009

AbstractChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is considered an auto‐immune disorder. We evaluated expression of pSTAT1, T‐bet, and pSTAT3 in circulating T‐cells, B‐cells, and monocytes and spontaneous production of interleukin‐17 (IL17), interferon‐gamma (IFNγ), and interleukin‐10 (IL10) by peripheral blood mononuclear cells (PBMCs) from 14 active CIDP patients compared with 6 patients with long‐lasting remission and 20 controls. Active disease patients showed higher pSTAT1, T‐bet, and pSTAT3 in CD4+ T‐cells than controls (p < 0.001, p = 0.0002, p = 0.0097, respectively) and remission patients (p < 0.001, p = 0.0036, p = 0.0008, respectively). pSTAT1, T‐bet, and pSTAT3 were also higher in monocytes from active CIDP patients than controls (p = 0.0011, p = 0.0041, p = 0.0413, respectively) and remission patients (p = 0.0073, p = 0.0274, p = 0.0251, respectively). Moreover in CD8+ T‐cells, pSTAT3 expression was higher in active CIDP patients than in remission patients (p = 0.0345) and in controls (p = 0.0023). IL17 and IFNγ production were significantly higher in active CIDP patients than in controls (p < 0.0395, p = 0.0010, respectively); IFNγ levels were higher also in remission CIDP patients (p = 0.0073). IL10 levels were higher in active phase patients than in controls (p = 0.0334). Our data suggest that pSTAT1, T‐bet, and pSTAT3 can be considered putative markers of disease activity and potential targets for specific therapies.
Funeral Sermons and Graveyard Poetry: The Ecstasy of Death and Bodily Resurrection
Authors: VAN LEEUWEN EVERT JAN 
Published: August 2009

AbstractThis article argues that Anglo‐American graveyard poetry is a form of religious poetry closely connected to the eighteenth‐century funeral sermon tradition. An analysis of graveyard poetry in the context of the funeral sermon reveals that the poems explore Christian themes of faith, doubt and the afterlife, in which death, the grave and its paraphernalia are not objects of fear and horror but objects of desire. Such an analysis also reveals that the authors of funeral sermons employed many similar poetic techniques when addressing their congregations, showing that sermons can be fruitfully approached as literary as well as religious texts.
Erasmus Darwin's Beautification of the Sublime: Materialism, Religion and the Reception of The Economy of Vegetation in the Early 1790s
Authors: LIST JULIA 
Published: August 2009

AbstractThis paper investigates the reception of Erasmus Darwin's The Economy of Vegetation, drawing on reviews, letters and poems by admirers to examine why the initial publication of this theologically ambiguous text was uncontroversial. Part of the explanation lies in the poem's perceived genre: the didactic nature poem, a traditionally religious form. A number of reviewers described the work in language that invokes a religious tradition of nature writing. However, this paper suggests that such a reading is difficult to sustain, given Darwin's portrayal of both human and natural processes in a way that continually undercuts the sublime aspects of creation.
William Godwin's Religious Sense
Authors: WESTON ROWLAND 
Published: August 2009

AbstractThe anarchist philosopher, novelist and historian William Godwin (1756‐1836) began life in a devout Dissenting or nonconformist family. As a young man he trained for the ministry, before losing his faith and turning atheist in 1792. Over the subsequent years of his long life Godwin continued to ponder the moral value of religious belief in general and of Christianity in particular. In his later religious writings Godwin insists that myth, superstition and religious belief are not intrinsically defective but are problematic only to the extent to which they undermine personal integrity and social solidarity.
Fear of Cultural Extinction and Psychopathology Among Mandaean Refugees: An Exploratory Path Analysis
Authors: Nickerson Angela , Bryant Richard A. , Brooks Robert , Steel Zachary , Silove Derrick 
Published: August 2009

The Mandaeans are a small religious community originating from Iraq and Iran who are facing the possibility of cultural extinction within the next few generations. This study aimed to examine the relationships between life experiences, psychopathology and fear of cultural extinction in Mandaean refugees. A survey was conducted of 315 adult Iraqi Mandaean refugees living in Australia. Past traumatic experiences and current resettlement difficulties were assessed. Mental health outcomes were also examined, including measures of posttraumatic stress disorder (PTSD) and depression. Fear of cultural extinction was measured by items developed in consultation with the Mandaean community. A path analysis was employed to investigate the relationship between trauma, living difficulties, PTSD, depression, and fear of cultural extinction. Results indicated that trauma and living difficulties impacted indirectly on fear of cultural extinction, while PTSD (and not depression) directly predicted levels of anxiety about the Mandaean culture ceasing to exist.The current findings indicate that past trauma and symptoms of posttraumatic stress contribute to fear of cultural extinction. Exposure to human rights violations enacted on the basis of religion has significant mental health consequences that extend beyond PTSD. The relationship between perception of threat, PTSD, and fear of cultural extinction is considered in the context of cognitive models of traumatic stress. Government immigration policy must prioritize the reunification of small, endangered groups to sustain cultural traditions. Treatment interventions implemented with cultural groups facing extinction should take into consideration anxiety about loss of culture.
Gender and Anxiety in Nepal: The Role of Social Support, Stressful Life Events, and Structural Violence
Authors: Kohrt Brandon A. , Worthman Carol M. 
Published: August 2009

Introduction: Throughout the world, anxiety disorders are 1.5–2 times more prevalent among women than men but the reasons for this gender disparity remain elusive. Despite frequent attribution to cultural roles of men and women, data regarding gendered risk factors in non‐Western settings are scant.Aims: This study evaluated the role of gender as a moderator (effect modifier) of stressful life events (SLEs) and social support on the risk of anxiety in Nepal. A cross‐sectional random sampling design was employed to recruit 316 persons in a rural community. The participants completed the Beck Anxiety Inventory (BAI), Stressful Life Events Rating Scale (SLERS), and a measure of social support.Results: The prevalence of anxiety differed by gender: 36.9% of women versus 20.4% of men endorsed anxiety symptoms above the validated cutoff for intervention (odds ratio [OR]= 2.3, 95% confidence interval [CI]= 1.4–3.8). The number of SLEs and levels of social support did not differ by gender, nor did gender moderate the relationship between SLEs and anxiety. Gender did moderate the relationship of social support with anxiety. Men who reported low social support had 3.5 times greater odds (95% CI = 1.4–10.7) of endorsing anxiety relative to men reporting high social support. Women exhibited no association of anxiety with social support.Conclusion: Women are at a greater risk of anxiety in Nepal. Social support moderates the risk of anxiety among men but not among women. Ethnography and mixed‐methods research are needed to identify other forms of support that may be protective for women and such factors should be promoted in gender‐focused mental health interventions.
Zoonotic risk of hepatitis E virus (HEV): A study of HEV infection in animals and humans in suburbs of Beijing
Authors: Chang Yibin , Wang Ling , Geng Jiabao , Zhu Yonghong , Fu Hongwei , Ren Furong , Li Lingjun , Wang Xiaojuan , Zhuang Hui 
Published: August 2009

Aim:  To investigate hepatitis E virus (HEV) infection among different animals and workers in pig farms and slaughterhouses, and analyze the genotype of HEV isolated in this study.Methods:  Serum samples were collected from adult swine, cows, sheep, younger swine (< 3 months), and workers in pig farms and slaughterhouses (professional group). Fecal samples were collected from younger swine in the south suburbs of Beijing. Anti‐HEV antibody was evaluated by direct sandwich enzyme immunoassay. HEV RNA was extracted from fecal samples and amplified by nested reverse transcription polymerase chain reaction (RT‐nPCR). The PCR products were sequenced, and the sequence homology and phylogenetics of the HEV strains isolated from swine were analyzed.Results:  The anti‐HEV positivity rates in adult swine, cows, sheep, younger swine, professional group and general population were 98.23% (222/226), 29.35% (54/184), 9.80% (20/207), 60.73% (99/164), 42.51% (105/247) and 20.29% (522/2572), respectively. The HEV RNA positivity rate of fecal samples was 22.89% (19/83) and 16/19 samples were positive for HEV RNA amplified with both primers, HEV open reading frame (ORF)1 and HEV ORF2. Sequence analysis of these 16 samples showed that there were two groups, designated BJ‐1 and BJ‐2. The nucleotide homology of BJ‐1 and BJ‐2 was 99%. Phylogenetic analysis indicated that both of these groups belonged to genotype 4d.Conclusion:  Workers in pig farms and slaughterhouses were more likely to contract HEV infection than the general population because of close contact with swine with a high prevalence of anti‐HEV.