bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self‐evolving oxidative stress with identifiable pre‐ and postmitochondrial phases in PC12 cells
Authors: Zhang Ganlin , Morin Christophe , Zhu Xiaoxin , Bao Huynh Minh , Ouidir Ouidja Mohand , Sepulveda‐Diaz Julia Elisa , Raisman‐Vozari Rita , Li Ping , Papy‐Garcia Dulce 
Published: November 2012

AbstractDuring the neurodegenerative process in several brain diseases, oxidative stress is known to play important roles in disease severity and evolution. Although early events of stress, such as increased lipid peroxidation and decreased superoxide dismutase, are known to characterize early onsets of these diseases, little is known about the events that participate in maintaining the chronic evolving phase influencing the disease progression in neurons. Here, we used differentiated PC12 cells to identify premitochondrial and postmitochondrial events occurring during the oxidative stress cascade leading to apoptosis. Our data indicate that an acute and strong oxidative impulse (500 μM H2O2, 30 min) can induce, in this model, a 24‐hr self‐evolving stress, which advances from a premitochondrial phase characterized by lysosomes and cathepsin B and D translocations to cytosol and early mitochondrial membrane hyperpolarization. This phase lasts for about 5 hr and is followed by a postmitochondrial phase distinguished by mitochondrial membrane depolarization, reactive oxygen species increase, caspase‐9 and caspase‐3 activations, and apoptosis. Inhibition of cathepsins B and D suggests that cells can be protected at the premitochondrial phase of stress evolution and that new cathepsins regulators, such as glycosaminoglycans mimetics, can be considered as new therapeutic prototypes for neurodegeneration. Insofar as early oxidative stress markers have been related to the early onset of neurodegeneration, strategies protecting cells at the premitochondrial phase of oxidative stress may have important therapeutic applications. © 2012 Wiley Periodicals, Inc.
Delayed leptin administration after stroke induces neurogenesis and angiogenesis
Authors: Avraham Y. , Dayan M. , Lassri V. , Vorobiev L. , Davidi N. , Chernoguz D. , Berry E. , Leker R.R. 
Published: November 2012

AbstractLeptin is a potent AMP kinase (AMPK) inhibitor that induces neuroprotection, neurogenesis, and angiogenesis when administered immediately after stroke. To dissociate these effects, we explored the effects of delayed administration of leptin, at 10 days after stroke onset, on neurogenesis and angiogenesis after stroke. Sabra mice underwent photothrombotic stroke and were treated with vehicle or leptin given either as a single dose or in triple dosing, 10 days later. Newborn cells were labeled with bromodeoxyuridine. Functional outcome was studied with the neurological severity score for 90 days poststroke, and the brains were then evaluated via immunohistochemistry. Final infarct volumes did not differ between the groups. Exogenous leptin led to significant increments in the number of proliferating BrdU+ cells in the subventricular zone and in the cortex abutting the lesion (2.5‐fold and 1.4‐fold, respectively). There were significant increments in the number of newborn neurons and glia (4‐ and 3.4‐fold, respectively) in leptin‐treated animals. Leptin also significantly increased the number of blood vessels in the perilesioned cortex. However, animals treated with leptin failed to demonstrate significantly better functional states. In conclusion, leptin induces neurogenesis and angiogenesis even when given late after stroke but does not lead to better functional outcome in this delayed‐treatment paradigm. These results suggest that the main beneficial effects of leptin after stroke are associated with its early neuroprotective role rather than with its proneurogenic or proangiogenic effects. © 2012 Wiley Periodicals, Inc.
Experimental epidural hematoma causes cerebral infarction and activates neocortical glial and neuronal genesis in adult guinea pigs
Authors: Pan Aihua , Li Ming , Gao Jun‐Yan , Xue Zhi‐Qin , Li Zhiyuan , Yuan Xian‐Yui , Luo Duan‐Wu , Luo Xue‐Gang , Yan Xiao‐Xin 
Published: November 2012

AbstractEpidural hematoma (EDH) is a type of life‐threatening traumatic brain injury. Little is known about the extent to which EDH may cause neural damage and regenerative response in the cerebral cortex. Here we attempted to explore these issues by using guinea pigs as an experimental model. Unilateral EDH was induced by injection of 0.1 ml autologous blood into the extradural space, with experimental effects examined at 7, 14, 30, and 60 days postlesion. An infarct developed in the cortex deep to the EDH largely after 7 days postlesion, with neuronal death occurred from layers I to V in the central infarct region, as evidenced by loss of immunoreactivity (IR) for neuron‐specific nuclear antigen (NeuN). Glial fibrillary acidic protein (GFAP) IR appeared as a cellular band surrounding the infarct and extending into the periinfarct cortex along the pia. Doublecortin (DCX) IR emerged in these same areas, with labeled cells appearing as astrocytic and neuronal profiles. DCX/GFAP colocalization was found in these regions commonly at 7 and 14 days postlesion, whereas DCX/NeuN‐colabeled neurons were detectable at 30 and 60 days postlesion. Subpopulations of GFAP‐, DCX‐, or NeuN‐immunoreactive cells colocalized with the endogenous proliferative marker Ki‐67 or bromodeoxyuridine (BrdU) after pulse‐chase with this birth‐dating marker. The results suggest that experimental EDH can cause severe neuronal loss, induce significant glial activation, and promote a certain degree of local neuronal genesis in adult guinea pig neocortex. These findings point to potential therapeutic targets for improving neuronal recovery in clinical management of EDH. © 2012 Wiley Periodicals, Inc.
Synucleins: Are they two‐edged swords?
Authors: Surguchov Andrei 
Published: November 2012

AbstractThe synuclein family consists of three distinct highly homologous genes, α‐synuclein, β‐synuclein, and γ‐synuclein, which have so far been found only in vertebrates. Proteins encoded by these genes are characterized by an acidic C‐terminal region and five or six imperfect repeat motifs (KTKEGV) distributed throughout the highly conserved N‐terminal region. Numerous data demonstrate that synucleins are implicated in two groups of the most devastating human disorders, i.e., neurodegenerative diseases (NDDs) and cancer. Mutations in the α‐synuclein gene are associated with familial forms of Parkinson's disease (PD), and accumulation of α‐synuclein inclusions is a hallmark of this disorder. In breast cancer, increased expression of γ‐synuclein correlates with disease progression. Conversely, some results indicate that the members of the synuclein family may have a protective effect. How might these small proteins combine such controversial properties? We present evidence that synuclein's features are basically regulated by two mechanisms, i.e., posttranslational modifications (PTMs) and the level of their expression. We also discuss a new, emerging area of investigation of synucleins, namely, their role in the cell‐to‐cell propagation of pathology. © 2012 Wiley Periodicals, Inc.
Guanosine protects against reperfusion injury in rat brains after ischemic stroke
Authors: Connell Barry J. , Di Iorio Patrizia , Sayeed Iqbal , Ballerini Patrizia , Saleh Monique C. , Giuliani Patricia , Saleh Tarek M. , Rathbone Michel P. , Su Caixin , Jiang Shucui 
Published: November 2012

AbstractAfter ischemic stroke, early thrombolytic therapy to reestablish tissue perfusion improves outcome but triggers a cascade of deleterious cellular and molecular events. Using a collaborative approach, our groups examined the effects of guanosine (Guo) in response to ischemic reperfusion injury in vitro and in vivo. In a transient middle cerebral artery occlusion (MCAO) in rats, Guo significantly reduced infarct volume in a dose‐dependent manner when given systemically either immediately before or 30 min, but not 60 min, after the onset of the 5.5‐hr reperfusion period. In a separate experiment, Guo significantly reduced infarct volume after 24 hr of reperfusion when administered 5 min before reperfusion. Western blot analysis did not reveal any significant changes either in endoplasmic reticulum (ER) stress proteins (GRP 78 and 94) or HSP 70 or in levels of m‐calpain. In vitro oxygen and glucose deprivation (OGD) significantly increased production of both reactive oxygen species (ROS) and interleukin‐8 (IL‐8) in the primary astrocytes. Guo did not alter ROS or IL‐8 production when given to the astrocytes before OGD. However, Guo when added to the cells prior to or 30 min after reperfusion significantly reduced IL‐8 release but not ROS formation. Our study revealed a dose‐ and time‐dependent protective effect of Guo on reperfusion injury in vitro and vivo. The mechanisms by which Guo exerts its effect are independent of unfolded proteins in ER or the level of intracellular calcium or ROS formation. However, the effect may be induced, at least partially, by inhibiting IL‐8, a marker of reperfusion‐triggered proinflammatory events. © 2012 Wiley Periodicals, Inc.
The use of ovarian vessels for microvascular tissue transfer in lower extremity limb salvage
Authors: Senchenkov Alex , Sim Franklin H. 
Published: November 2012

AbstractLimb salvage procedures in previously operated, radiated, and vessel‐depleted fields rely heavily on the use of microvascular tissue transfer. This report illustrates the feasibility of the use of ovarian vessels for the revascularization of a free flap. We have achieved success with the use of rectus abdominis muscle free flap for coverage of exposed vascular reconstruction in the 75‐year‐old soft tissue sarcoma patient with twice chemoradiated femoral and hypogastric defect, preventing external hemipelvectomy. © 2012 Wiley Periodicals, Inc. Microsurgery, 2013.
Quantitative Evaluation and Prediction of Drug Effects and Toxicological Risk Using Mechanistic Multiscale Models
Authors: Niklas Jens , Diaz Ochoa Juan G , Bucher Joachim , Mauch Klaus 
Published: November 2012

AbstractIntegrating in vitro and in silico approaches has great potential for reducing experimental effort and delivering know‐how and intellectual property in drug development. Here, we focus on a possible framework for multiscale modeling in pharmaceutical drug development. Looking at the modeling frameworks at different scales, it is obvious that choosing the proper level of complexity and abstraction is not a trivial task. At cellular level, we consider that the application of validated kinetic models of cellular toxicity mechanisms of drugs is particularly important for deriving valid predictions. These kinetic models can be applied for integrating inter‐individual differences, e.g. obtained from data measured in surgical liver samples, into predictions of drug effects. Challenges identified include (i) the development of sufficiently detailed, structured organ models, (ii) definition of multiscale models that can be efficiently handled by available super‐computing facilities, and (iii) availability of validated cell‐type and organ‐specific kinetic metabolic models. Multiscale models can streamline drug development by facilitating the design of experiments and trials, by providing and testing hypotheses, and by reducing time and costs due to less experiments and improved decision‐making. In this review, we discuss the required pieces, possibilities, and challenges in multiscale modeling for the prediction of drug effects.
Identifying Activity Cliff Generators of PPAR Ligands Using SAS Maps
Authors: Méndez‐Lucio Oscar , Pérez‐Villanueva Jaime , Castillo Rafael , Medina‐Franco José L. 
Published: November 2012

AbstractStructure‐activity relationships (SAR) of compound databases play a key role in hit identification and lead optimization. In particular, activity cliffs, defined as a pair of structurally similar molecules that present large changes in potency, provide valuable SAR information. Herein, we introduce the concept of activity cliff generator, defined as a molecular structure that has a high probability to form activity cliffs with molecules tested in the same biological assay. To illustrate this concept, we discuss a case study where Structure‐Activity Similarity maps were used to systematically identify and analyze activity cliff generators present in a dataset of 168 compounds tested against three peroxisome‐proliferator‐activated receptor (PPAR) subtypes. Single‐target and dual‐target activity cliff generators for PPARα and δ were identified. In addition, docking calculations of compounds that were classified as cliff generators helped to suggest a hot spot in the target protein responsible of activity cliffs and to analyze its implication in ligand‐enzyme interaction.
Early hematopoietic stem cell transplant is associated with favorable outcomes in children with MDS
Authors: Smith Angela R. , Christiansen Ellen C. , Wagner John E. , Cao Qing , MacMillan Margaret L. , Stefanski Heather E. , Trotz Barbara A. , Burke Michael J. , Verneris Michael R. 
Published: November 2012

AbstractBackgroundAlthough hematopoietic stem cell transplantation (HSCT) is the treatment of choice for childhood myelodysplastic syndrome (MDS), there is no consensus regarding patient or disease characteristics that predict outcomes.ProcedureWe reviewed 37 consecutive pediatric MDS patients who received myeloablative HSCT between 1990 and 2010 at a single center.ResultsTwenty had primary MDS and 17 had secondary MDS. Diagnostic cytogenetics included monosomy 7 (n = 21), trisomy 8 (n = 7) or normal/other (n = 8). According to the modified WHO MDS classification, thirty had refractory cytopenia and seven had refractory anemia with excess blasts. IPSS scores were: low risk (n = 1), intermediate‐1 (n = 15), and intermediate‐2 (n = 21). OS and DFS at 10 years in the entire cohort was 53% and 45%. Relapse at 10 years was 26% and 1 year TRM was 25%. In multivariate analysis, factors associated with improved 3 years DFS were not receiving pre‐HSCT chemotherapy (RR = 0.30, 95% CI 0.10–0.88; P = 0.03) and a shorter interval (<140 days) from time of diagnosis to transplant (RR = 0.27, 95% CI 0.09–0.80; P = 0.02). Three years DFS in patients who did not receive pre‐HSCT chemotherapy and those who had a shorter interval to transplant (n = 16) was 80%.ConclusionThese results suggest that children with MDS should be referred for allogeneic HSCT soon after diagnosis and that pre‐HSCT chemotherapy does not appear to improve outcomes. Pediatr Blood Cancer 2013; 60: 705–710. © 2012 Wiley Periodicals, Inc.
Successful liver transplantation in an infant with stage 4S(M) neuroblastoma
Authors: Steele Melanie , Jones Nicola L. , Ng Vicky , Kamath Binita , Avitzur Yaron , Chami Rose , Cutz Ernest , Fecteau Annie , Baruchel Sylvain 
Published: November 2012

AbstractWe report a 2.5‐month‐old infant with bilateral adrenal neuroblastoma, stage 4S(M), with liver metastases and chemotherapy‐induced veno‐occlusive disease leading to cirrhosis requiring liver transplantation. Despite unknown tumour histology and MYCN‐amplification status, we proceeded with liver transplant. This decision was based on clinical suspicion that our patient was MYCN‐negative due to significant tumour regression, and was supported by evidence indicating that MYCN‐amplification is rare in infants with favourable‐stage neuroblastoma. This is the second case report of neuroblastoma requiring liver transplantation; however, in the previously reported case, the diagnosis of neuroblastoma was not established until after transplantation. We discuss this unique case to justify the potential use of life‐saving liver transplants in infants with neuroblastoma. Pediatr Blood Cancer 2013; 60: 515–517. © 2012 Wiley Periodicals, Inc.
Pharmacokinetic interaction between methotrexate and chloral hydrate
Authors: Dao Kim , Ivanyuk Anton , Buclin Thierry , Beck‐Popovic Maja , Diezi Manuel 
Published: November 2012

AbstractWe report the case of a drug interaction between methotrexate (MTX) and chloral hydrate (CH) observed in a child treated for acute leukemia. Significantly slower MTX clearance and increased MTX exposure occurred on the first three courses of a high‐dose chemotherapy when co‐administered with CH despite normal renal function, adequate hydration, and alkalinization. Mean MTX area under the curve associated with CH administration was 1,134 µmol hours/L, compared to 608 µmol hours/L after discontinuation of CH. This interaction possibly resulted from a competition between anionic CH metabolites and MTX for renal tubular excretion. Pediatr Blood Cancer 2013; 60: 518–520. © 2012 Wiley Periodicals, Inc.
Mental health disorders influence admission rates for pain in children with sickle cell disease
Authors: Myrvik Matthew P. , Burks Lisa M. , Hoffman Raymond G. , Dasgupta Mahua , Panepinto Julie A. 
Published: November 2012

AbstractBackgroundPatients with sickle cell disease (SCD) experience a broad range of mental health disorders placing them at risk for more complicated hospitalizations for pain. The current study examined the impact of mental health disorders on admission rates and hospital length of stay (LOS) for vaso‐occlusive pain events (VOE) in pediatric patients with SCD.ProcedurePatients (5–18 years old) with a primary discharge diagnosis of SCD with crisis were acquired through the Pediatric Health Information System and categorized by history of mental health disorders (mood disorder, anxiety disorder, disruptive behavior disorder, and substance use disorder). Using a retrospective cohort design, hospital admission rates for VOE were examined as the primary outcome and LOS as a secondary outcome.ResultsA total of 5,825 patients accounted for 23,561 admissions for SCD with crisis with approximately 8% of the patients having a mental health diagnosis. Longer LOS was found among patients with a history of any mental health diagnosis (P < 0.0001) and within the mood disorder (P < 0.0001), anxiety disorder (P < 0.0001), and substance use disorder (P = 0.01) subtypes. Hospital admissions rates for VOE were higher among patients with a history of any mental health diagnosis (P < 0.0001) and within the mood disorder (P < 0.0001), anxiety disorder (P < 0.0001), disruptive behavior disorder (P = 0.002), and substance use disorder (P < 0.0001) subtypes.ConclusionsPediatric patients with SCD and a history of a mental health diagnosis have longer LOS and higher admission rates for management of VOE. Ultimately, these findings suggest that mental health pose a challenge to the management of sickle cell pain. Pediatr Blood Cancer 2013; 60: 1211–1214. © 2012 Wiley Periodicals, Inc.
Cationic polymerization of isoprene using zinc halides as co‐initiators: towards well‐defined oligo(isoprene)s under mild conditions
Authors: Rozentsvet Victor A , Kozlov Valery G , Ziganshina Elza F , Boreiko Natalya P , Kostjuk Sergei V 
Published: November 2012

AbstractThe activity of ZnX2‐based initiating systems (X = Cl, Br, I) in the cationic polymerization of isoprene was studied. The highest activity was achieved when co‐initiator (ZnX2) was solubilized in a minimal amount of strongly coordinating solvent such as diethyl ether or acetone and when trichloroacetic acid was used as an initiator. It is shown that the polymerization rate increased in the series ZnI2 < ZnCl2 < ZnBr2. An increase of initiator concentration and temperature also led to an increase of the polymerization rate. The obtained polyisoprenes did not contain high‐molecular‐weight and insoluble fractions and were characterized by low number‐average molecular weight and relatively narrow molecular weight distribution. Unsaturation of polyisoprene decreased with an increase of monomer conversion and reaction temperature. The unsaturated part of the polyisoprene chain possessed predominantly 1,4‐trans microstructure with regular and inverse addition, whereas the 1,2‐ and 3,4‐isomers were present as minor components. It is shown that the synthesized low‐molecular‐weight polyisoprenes are effective plasticizers for rubber compounds in the manufacture of tyres. © 2012 Society of Chemical Industry
Antibacterial and biocompatible surfaces based on dopamine autooxidized silver nanoparticles
Authors: Sureshkumar Manthiriyappan , Siswanto Dessy Yovita , Chen Yong‐Cin , Lee Cheng‐Kang , Wang Meng‐Jiy 
Published: November 2012

AbstractA facile and green method is proposed to immobilize silver nanoparticles (AgNPs) showing antibacterial and biocompatible properties on surfaces of substrates. The adhesive and reductive polydopamine (Pdop) coating was applied on the substrates such as polyethylene, glass, poly(methyl methacrylate), and poly(lactic‐co‐glycolic acid) by simply dipping into dopamine solutions. AgNPs of 50–70 nm formed uniformly on the Pdop‐coated surfaces after immersing in silver nitrate solution where the density of AgNPs was modulated by Pdop immobilization time. Antibacterial efficacy, lactate dehydrogenase assay, and cell morphology observed by microscopy indicated that the as‐prepared AgNPs deposited on Pdop/substrates possessed effective biocidal properties and did not inhibit the growth of L‐929 cells mouse fibroblasts. The proposed method can be easily applied on different substrates and revealed good biocompatibility, which could be further developed for applications in biomaterials. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2013
Ethylmalonic acid modulates Na+, K+‐ATPase activity and mRNA levels in rat cerebral cortex
Authors: Schuck Patrícia Fernanda , De Assis Dênis Reis , Viegas Carolina Maso , Brandão Pereira Talita Carneiro , Machado Jéssica Luca , Furlanetto Camila Brulezi , Bogo Mauricio Reis , Streck Emilio Luiz , Ferreira Gustavo Costa 
Published: November 2012

AbstractEthylmalonic acid (EMA) accumulates in tissues of patients affected by short‐chain acyl‐CoA dehydrogenase deficiency and ethylmalonic encephalopathy, illnesses characterized by variable neurological symptoms. In this work, we investigated the in vitro and in vivo EMA effects on Na+,K+‐ATPase (NAK) activity and mRNA levels in cerebral cortex from 30‐day‐old rats. For in vitro studies, cerebral cortex homogenates were incubated in the presence of EMA at 0.5, 1, or 2.5 mM concentrations for 1 h. For in vivo experiments, animals received three subcutaneous EMA injections (6 μmol g−1; 90‐min interval) and were killed 60 min after the last injection. After that, NAK activity and its mRNA expression were measured. We observed that EMA did not affect this enzyme activity in vitro. In contrast, EMA administration significantly increased NAK activity and decreased mRNA NAK expression as assessed by semiquantitative reverse transcriptase polymerase chain reaction when compared with control group. Considering the high score of residues prone to phosphorylation on NAK, this profile can be associated with a possible regulation by specific phosphorylation sites of the enzyme. Altogether, the present results suggest that NAK alterations may be involved in the pathophysiology of brain damage found in patients in which EMA accumulates. Synapse, 2013. © 2012 Wiley Periodicals, Inc.