bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ketorolac tromethamine: stereo‐specific pharmacokinetics and single‐dose use in postoperative infants aged 2–6 months
Authors: Lynn Anne M. , Bradford Heidi , Kantor Eric D. , Andrew Marilee , Vicini Paolo , Anderson Gail D. 
Published: December 2010

AbstractObjective:  We determined the postoperative pharmacokinetics (PK), safety, and analgesic effects of ketorolac in 14 infants (aged <6 months) receiving a single intravenous (IV) administration of racemic ketorolac or placebo.Background:  Information on the PK of ketorolac in infants is limited. Unblinded studies suggest ketorolac may be useful in infants.Methods:  This double‐blinded, placebo‐controlled study enrolled 14 infants (aged <6 months) postoperatively. At 6–18 h after surgery, infants were randomized to receive placebo, 0.5 mg·kg−1, or 1 mg·kg−1 ketorolac IV. All infants received morphine sulfate as needed for pain control. Blood was collected up to 12‐h postdosing. Analysis used noncompartmental and compartmental population modeling methods.Results:  In addition to noncompartmental and empirical Bayes PK modeling, data were integrated with a previously studied data set comprising 25 infants and toddlers (aged 6–18 months). A two‐compartmental model described the comprehensive data set. The population estimates of the R (+) isomer were (%CV): central volume of distribution 1130 (10%) ml, peripheral volume of distribution 626 (25%) ml, and clearance from the central compartment 7.40 (8%) ml·min−1. Those of the S (−) isomer were 1930 (15%) ml, 319 (58%) ml, and 39.5 (13%) ml·min−1. Typical elimination half‐lives were 191 and 33 min, respectively. There was a trend for increased clearance and central volume with increasing age and weight. The base model suggested that clearance of the S (−) isomer was weakly related to age; however, when body size adjustment was added to the model, no covariates were significant. Safety assessment showed no changes in renal or hepatic function tests, surgical drain output, or continuous oximetry between groups. Cumulative morphine administration showed large inter‐patient variability and was not different between groups.Conclusion:  Stereo‐isomer‐specific clearance of ketorolac in infants (aged 2–6 months) shows rapid elimination of the analgesic S (−) isomer as reported in infants aged 6–18 months. No adverse effects were seen after a single IV ketorolac dose.
Entrepreneurial Orientation: A Theoretical and Empirical Examination of the Consequences of Differing Construct Representations
Authors: George Bradley A. 
Published: December 2010

abstractThere has been much debate in the literature over the nature of the entrepreneurial orientation (EO) construct regarding its dimensionality and whether or not the dimensions of the construct are independent. This paper examines two different measurement models of the EO construct that have been put forth in the literature and describes the implications of each model with regard to these issues as well as their broader theoretical and practical implications for studies regarding EO. Finally, a Monte Carlo simulation shows that misspecification of the construct can inflate structural parameter estimates by over 240 per cent and critical ratios by up to 68 per cent, illustrating the threat to the statistical conclusion validity studies and emphasizing the importance of congruence between the theoretical definition of the construct and its measurement.
Low‐cumulative dose isotretinoin treatment in mild‐to‐moderate acne: efficacy in achieving stable remission
Authors: Borghi A. , Mantovani L. , Minghetti S. , Giari S. , Virgili A. , Bettoli V. 
Published: December 2010

AbstractBackground  Aimed at the reduction of post‐treatment relapse of severe acne, the cumulative dose of oral isotretinoin should be ≥120 mg/kg. However, data on the appropriate oral isotretinoin treatment regimen in mild and moderate acne are lacking.Objective  The purpose of this study was to determine the efficacy of an isotretinoin‐sparing protocol in inducing permanent remission of mild and moderate acne.Methods  In this open, prospective, non‐comparative study, 150 patients affected with mild‐to‐moderate acne were treated with isotretinoin until complete recovery and for a further month of treatment, independent of the total cumulative dose reached. Patients then underwent a 1‐year maintenance therapy with adapalene 0.1% cream. Patients were followed up for a further year, without any treatment.Results  A total of 139 patients completed the study. Overall, patients received a mean of 80.92 mg/kg cumulative dose of isotretinoin. In the 2‐year follow‐up, relapse only appeared in 13 patients (9.35%).Conclusion  Comparing our findings with published data, this isotretinoin‐sparing regimen was shown to be effective in inducing stable remission and preventing acne relapses in patients with mild‐to‐moderate acne. Low‐cumulative dose regimens may potentially lead to a lower incidence of side‐effects and to lower costs than higher doses.
Gadolinium‐induced oxidative stress triggers endoplasmic reticulum stress in rat cortical neurons
Authors: Xia Qing , Feng Xudong , Huang Haifeng , Du Lingyan , Yang Xiaoda , Wang Kui 
Published: December 2010

J. Neurochem. (2011) 117, 38–47.AbstractIntroduction of Gadolinium (Gd) to the nervous system is linked to the development of neurotoxicity involving both oxidative and endoplasmic reticulum (ER) stress. Gd levels (0.2–20 μm) in the form of gadolinium trichloride (GdCl3) cause neurotoxicity in vitro. We investigated the signaling pathways in primary cultured rat cortical neurons and tested whether GdCl3 induced oxidative and ER stress. Results showed that Gd‐induced neural cell death followed a rapid accumulation of intracellular reactive oxygen species. In addition, Gd exposure resulted in spliced X‐box binding protein 1 mRNA and increased expression of binding immunoglobulin protein, thus activating transcription factor 4 (ATF4), ATF6, and C/EBP homologous protein mRNA. Up‐regulated expression of binding immunoglobulin protein is a hallmark of ER stress and C/EBP homologous protein is an ER stress‐related pro‐apoptotic transcription factor. Activation of ER stress downstream substrates, inositol‐requiring kinase 1 and ATF6, was also observed in Gd‐treated cells. The neurotoxic effects of Gd were blocked by the antioxidant N‐acetylcysteine. Results demonstrated that Gd‐induced cytotoxicity in neurons occurs via oxidative injury and ER stress‐related signal transduction, thus offering new insight into the neurotoxicology of gadolinium.
p38 Mitogen‐activated protein kinase and PI3‐kinase are involved in up‐regulation of mu opioid receptor transcription induced by cycloheximide
Authors: Kim Do Kyung , Hwang Cheol Kyu , Wagley Yadav , Law Ping‐Yee , Wei Li‐Na , Loh Horace H. 
Published: December 2010

J. Neurochem. (2011)116, 1077–1087.AbstractDespite several decades of efforts to develop safer, efficacious, and non‐addictive opioids for pain treatment, morphine remains the most valuable painkiller in contemporary medicine. Morphine and endogenous mu opioid peptides exert their pharmacological actions mainly through the mu opioid receptor (MOR). Analgesic effects of opioids in animals are dependent on the MOR expression levels, as demonstrated by studies of MOR‐knockout mice (homo/heterozygotes) and MOR‐less expressing mice. Surprisingly, in the course of our investigation to understand the mechanisms involved in the regulation of MOR gene expression, cycloheximide (CHX), a known protein synthesis inhibitor, markedly induced accumulation of MOR mRNAs in both MOR‐negative and ‐positive cells. This induction was blocked by inhibitors of phosphoinositide 3‐kinase (PI3‐K) and p38 MAPK, but not by a p42/44 MAPK inhibitor.In vitro, CHX was found to activate the MOR promoter and this activation was suppressed by inhibition of PI3‐K. The transcriptional activator Sox18 was recruited to the MOR promoter in CHX‐treated cells and this recruitment was also inhibited by the PI3‐K and p38 MAPK inhibitors, Ly294002 and SB203580, respectively. Consistently, acetylation of histone H3 and induction of H3‐K4 methylation were detected while reductions of histone deacetylase 2 binding and H3‐K9 methylation were observed on the promoter. Furthermore, the MOR mRNA accumulation was almost completely inhibited in the presence of actinomycin‐D, indicating that this effect occurs mainly through activation of the transcriptional machinery. These observations suggest that CHX directly induces MOR gene transcription by recruiting the active transcription factor Sox18 to the MOR promoter through PI3‐ and/or p38 MAPK pathways.
Dramatic increase in readthrough acetylcholinesterase in a cellular model of oxidative stress
Authors: Härtl Ricarda , Gleinich Anne , Zimmermann Martina 
Published: December 2010

J. Neurochem.(2011)116, 1088–1096.AbstractModerate, transient oxidative stress is achieved in SH‐SY5Y cells using tertiary butylhydroperoxide as oxidant. Over a recovery period of 24 h, the enzymatic activity and protein levels of the acetylcholinesterase (AChE) splice variants tailed AChE (AChE‐T) and readthrough AChE (AChE‐R) are monitored. Their time‐dependent correlation to pro‐ and anti‐apoptotic factors, namely caspase 3 and Bcl‐2, respectively, as well as lactate dehydrogenase release as a measure of cell viability is assessed. A distinctly different expression pattern of AChE‐T as compared with AChE‐R is recorded, in that AChE‐T shows only a very slight increase over a 6 h time period. In contrast, AChE‐R rises continuously during the recovery period, reaching peak intracellular levels that are up to six times higher than control levels 3–4 h post‐stress, and is released from cells in substantial amounts. Moreover, anti‐apoptotic Bcl‐2 increases significantly, peaking 2–3 h after this AChE‐R peak has occurred. We believe this study presents the first work that demonstrates – without relying on techniques of over‐expression – the time‐dependent correlation between apoptotic processes and related rescue mechanisms involving AChE isoforms in a neuronal cell line.
Oxidative stress‐induced oligomerization inhibits the activity of the non‐receptor tyrosine phosphatase STEP61
Authors: Deb Ishani , Poddar Ranjana , Paul Surojit 
Published: December 2010

J. Neurochem.(2011)116, 1097–1111.AbstractThe neuron‐specific tyrosine phosphatase STriatal Enriched Phosphatase (STEP) is emerging as an important mediator of glutamatergic transmission in the brain. STEP is also thought to be involved in the etiology of neurodegenerative disorders that are linked to oxidative stress such as Alzheimer’s disease and cerebral ischemia. However, the mechanism by which oxidative stress can modulate STEP activity is still unclear. In this study, we have investigated whether dimerization may play a role in regulating the activity of STEP. Our findings show that STEP61, the membrane associated isoform, can undergo homodimerization under basal conditions in neurons. Dimerization of STEP61involves intermolecular disulfide bond formation between two cysteine residues (Cys 65 and Cys 76 respectively) present in the hydrophobic region at the N‐terminus specific to STEP61. Oxidative stress induced by hydrogen peroxide leads to a significant increase in the formation of dimers and higher‐order oligomers of STEP61. Using two substrates,para‐nitrophenylphosphate and extracellular‐regulated kinase MAPK we further demonstrate that oligomerization leads to a significant reduction in its enzymatic activity.
Dendritic trafficking of brain‐derived neurotrophic factor mRNA: regulation by translin‐dependent and ‐independent mechanisms
Authors: Wu Yen‐Ching , Williamson Rebecca , Li Zhi , Vicario Annalisa , Xu Jerry , Kasai Masataka , Chern Yijuang , Tongiorgi Enrico , Baraban Jay M. 
Published: December 2010

J. Neurochem. (2011) 116, 1112–1121.AbstractDendritic trafficking and translation of brain‐derived neurotrophic factor (BDNF) transcripts play a key role in mediating synaptic plasticity. Recently, we demonstrated that siRNA‐mediated knockdown of translin, an RNA‐binding protein, impairs KCl‐induced dendritic trafficking of BDNF mRNA in cultured hippocampal neurons. We have now assessed whether translin deletion impairs dendritic trafficking of BDNF mRNA in hippocampal neurons in vivo. We have found that translin and its partner protein, trax, undergo dendritic translocation in response to treatment with pilocarpine, a pro‐convulsant muscarinic agonist that increases dendritic trafficking of BDNF mRNA in hippocampal neurons. In translin knockout mice, the basal level of dendritic BDNF mRNA is decreased in CA1 pyramidal neurons. However, translin deletion does not block pilocarpine’s ability to increase dendritic trafficking of BDNF mRNA indicating that the requirement for translin in this process varies with the stimulus employed to drive it. Consistent with this inference, we found that dendritic trafficking of BDNF mRNA induced by bath application of recombinant BDNF in cultured hippocampal neurons, is not blocked by siRNA‐mediated knockdown of translin. Taken together, these in vivo and in vitro findings indicate that dendritic trafficking of BDNF mRNA can be mediated by both translin‐dependent and ‐independent mechanisms.
SynArfGEF is a guanine nucleotide exchange factor for Arf6 and localizes preferentially at post‐synaptic specializations of inhibitory synapses
Authors: Fukaya Masahiro , Kamata Akifumi , Hara Yoshinobu , Tamaki Hideaki , Katsumata Osamu , Ito Naoki , Takeda Shin’ichi , Hata Yutaka , Suzuki Tatsuo , Watanabe Masahiko , Harvey Robert J. , Sakagami Hiroyuki 
Published: December 2010

J. Neurochem. (2011) 116, 1122–1137.AbstractSynArfGEF, also known as BRAG3 or IQSEC3, is a member of the brefeldin A‐resistant Arf‐GEF/IQSEC family and was originally identified by screening for mRNA species associated with the post‐synaptic density fraction. In this study, we demonstrate that synArfGEF activates Arf6, using Arf pull down and transferrin incorporation assays. Immunohistochemical analysis reveals that synArfGEF is present in somata and dendrites as puncta in close association with inhibitory synapses, whereas immunoelectron microscopic analysis reveals that synArfGEF localizes preferentially at post‐synaptic specializations of symmetric synapses. Using yeast two‐hybrid and pull down assays, we show that synArfGEF is able to bind utrophin/dystrophin and S‐SCAM/MAGI‐2 scaffolding proteins that localize at inhibitory synapses. Double immunostaining reveals that synArfGEF co‐localizes with dystrophin and S‐SCAM in cultured hippocampal neurons and cerebellar cortex, respectively. Both β‐dystroglycan and S‐SCAM were immunoprecipitated from brain lysates using anti‐synArfGEF IgG. Taken together, these findings suggest that synArfGEF functions as a novel regulator of Arf6 at inhibitory synapses and associates with the dystrophin‐associated glycoprotein complex and S‐SCAM.
Individualistic species limitations of climate‐induced range expansions generated by meso‐scale dispersal barriers
Authors: Keith Sally A. , Herbert Roger J.H. , Norton Paul A. , Hawkins Stephen J. , Newton Adrian C. 
Published: December 2010

AbstractAim  Evidence indicates that species are responding to climate change through distributional range shifts that track suitable climatic conditions. We aim to elucidate the role of meso‐scale dispersal barriers in climate‐tracking responses.Location  South coast of England (the English Channel).Methods  Historical distributional data of four intertidal invertebrate species were logistically regressed against sea surface temperature (SST) to determine a climate envelope. This envelope was used to estimate the expected climate‐tracking response since 1990 along the coast, which was compared with observed range expansions. A hydrodynamic modelling approach was used to identify dispersal barriers and explore disparities between expected and observed climate tracking.Results  Range shifts detected by field survey over the past 20 years were less than those predicted by the changes that have occurred in SST. Hydrodynamic model simulations indicated that physical barriers produced by complex tidal currents have variably restricted dispersal of pelagic larvae amongst the four species.Main conclusions  We provide the first evidence that meso‐scale hydrodynamic barriers have limited climate‐induced range shifts and demonstrate that life history traits affect the ability of species to overcome such barriers. This suggests that current forecasts may be flawed, both by overestimating range shifts and by underestimating climatic tolerances of species. This has implications for our understanding of climate change impacts on global biodiversity.
THE DAYLIGHT SAVING TIME ANOMALY IN STOCK RETURNS: FACT OR FICTION?
Authors: Gregory‐Allen Russell , Jacobsen Ben , Marquering Wessel 
Published: December 2010

AbstractStock market returns in 22 markets around the world show no evidence of a daylight saving time effect. Returns on the days following a switch from or to daylight saving time do not behave any differently from stock market returns on any other day of the week or month. These results reject earlier conclusions in the literature—based on less data—that investors’ mood changes induced by changes in sleep patterns significantly affect stock returns.
CORPORATE HEDGING AND SHAREHOLDER VALUE
Authors: Aretz Kevin , Bartram Söhnke M. 
Published: December 2010

AbstractAlthough theory suggests that corporate hedging can increase shareholder value in the presence of capital market imperfections, empirical studies show overall mixed support for rationales of hedging with derivatives. Although various empirical challenges and limitations advise some caution with regard to the interpretation of the existing evidence, the results are consistent with derivatives use being just one part of a broader financial strategy that considers the type and level of financial risks, the availability of risk management tools, and the operating environment of the firm. Moreover, corporations rely heavily on pass‐through, operational hedging, and foreign currency debt to manage financial risk.
DETERMINANTS OF CAPITAL STRUCTURE IN BUSINESS START‐UPS: THE ROLE OF NONFINANCIAL STAKEHOLDER RELATIONSHIP COSTS
Authors: Franck Tom , Huyghebaert Nancy 
Published: December 2010

AbstractAccording to the finance literature, nonfinancial stakeholders (NFS), such as customers, suppliers, and employees, take into account their expected liquidation costs when dealing with a firm. In this framework, firms can influence their probability of liquidation by choosing an appropriate capital structure. Also, the literature suggests NFS bargaining power may affect firm financing decisions. In the current article we investigate these ideas for initial financing decisions by business start‐ups, where ex ante failure risk is high and NFS must decide whether to make relationship‐specific investments. We find that start‐ups imposing larger costs on their NFS following liquidation significantly reduce leverage. This effect is strengthened when suppliers have greater bargaining power. We also document a marginally negative effect of NFS liquidation costs on the proportion of bank loans. Finally, business start‐ups rely less on bank loans when customers and suppliers are in a powerful bargaining position.
Comparing Partial and Total Tibial‐Nerve Axotomy: Long‐Term Effects on Prevalence and Location of Evoked Pain Behaviors
Authors: Unal‐Cevik Isin , Oaklander Anne Louise 
Published: December 2010

AbstractMonophasic (one‐time) nerve injuries heal without clinically significant residua in most cases, but rare individuals are left with neuropathic pain, even after seemingly minor lesions. The effects of lesion size on risk for chronic pain persistence are not well understood, particularly as concerns the complex regional pain syndrome, which is defined in part by pain “disproportionate” to the severity of the causative lesion, and extending outside the autonomous territory of a single nerve. To better clarify the expected prevalence of pain behaviors after nerve injury, we compared the effects in rats of different‐sized axotomies on the prevalence and location of evoked pain behaviors. To highlight clinical relevance, we also describe a patient with iatrogenic tibial‐nerve injury causing similar chronic neuralgia. Adult male Sprague‐Dawley rats were anesthetized and had either 1/3, 2/3 or their entire left tibial nerves tightly ligated at two sites just below the sciatic trifurcation and the interposed nerve was cut. Unoperated rats provided controls. Sensory function in the tibial and sural‐innervated territories of both plantar hindpaws was assessed for as long as 6 months postoperatively. Soon after surgery, evoked pain behavior developed in the ipsilesional sural‐innervated site in a subset of axotomized rats and recovery was variable. The relationship between lesion size and prevalence and severity of hyperalgesia varied for different pain behaviors, with pinprick hyperalgesia clearly more likely after larger axotomies. In summary, partial tibial‐nerve injury in rats models human disease and suggests that expectations of proportionality between lesion size and development of neuropathic pain may need revision.
Percutaneous Atrial Shunt Closure Using the Novel Occlutech Figulla Device: 6‐Month Efficacy and Safety
Authors: VAN DEN BRANDEN BEN J. L. , POST MARTIJN C. , PLOKKER HERBERT W. M. , TEN BERG JURRIËN M. , SUTTORP MAARTEN J. 
Published: December 2010

Background:
The Occlutech Figulla Occluder is a new innovative device for percutaneous closure of a patent foramen ovale (PFO) and an atrial septum defect (ASD). We describe the safety and efficacy of this new device at 6‐month follow‐up.
Methods:
All 82 consecutive patients (51% female, mean age 49.0 ± 13.6 years) who underwent percutaneous PFO (n = 48) or ASD (n = 34) closure between October 2008 and October 2009 were included.
Results:
Implantation success was 100%. The in‐hospital complications were two new onset supraventricular tachycardia (SVT) (2.4%, both ASD patients), nine minimal groin hematoma's (11.0%, 4 PFO and 5 ASD patients), and one transient ST elevation during the procedure (1.2%, ASD patient). During 6 months follow‐up (n = 79), no major complications or reoccurrences of cerebral thrombo‐embolic events did occur. Seven patients (8.9%, 6 PFO and 1 ASD patient) experienced a new SVT. One patient developed a recurrent cerebral hemorrhage 5 months after ASD closure, which appeared not to be related to the procedure. Using contrast transthoracic echocardiography 6 months after PFO closure (n = 45), a residual shunt was present in 30.2% of the patients (small 25.6%, moderate 4.6%, severe 0%). In the ASD group (n = 34), a residual shunt was observed in 32.5% (small 17.7%, moderate 14.7%, severe 2.9%).
Conclusion:
The Occlutech Figulla Occluder appears to be easy to use, effective, and safe for percutaneous closure of PFO and ASD. We report a low complication rate but a relative high percentage of small residual shunts 6 months after closure. (J Interven Cardiol 2011;24:264–270)