bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained improvement in joint pain and nail symptoms with etanercept therapy in patients with moderate‐to‐severe psoriasis
Authors: Luger TA , Barker J , Lambert J , Yang S , Robertson D , Foehl J , Molta CT , Boggs R 
Published: May 2009

AbstractBackground  To determine the prevalence of joint and nail symptoms, impact of these symptoms on health‐related quality of life (HR‐QoL), and the effects of etanercept on them in patients with moderate‐to‐severe plaque psoriasis.Methods  In CRYSTEL, patients with psoriasis received etanercept continuously (n = 357) or as paused therapy (n = 363) for 54 weeks. In post hoc analyses, baseline characteristics and after‐treatment changes were evaluated in patients with baseline joint pain or nail psoriasis, pooling across treatment groups. Assessments of symptom severity and HR‐QoL included the Subject Global Assessment question on joint pain, NAPSI, DLQI and EQ‐5D.Results  Of 711 patients, 64% reported joint pain and 79% nail psoriasis at baseline. Patients with baseline joint pain or nail psoriasis had significantly worse HR‐QoL than unaffected patients. Mean baseline differences between patients with and without joint pain in DLQI (3.3), EQ‐5D utility (0.2), and EQ‐5D VAS (7.3) were clinically meaningful. In patients with nail psoriasis, a clinically meaningful difference in EQ‐5D VAS (5.0) was seen. Etanercept significantly improved symptom severity and HR‐QoL. Patients with joint pain had improvements of 47%, 61%, 29%, and 23% in mean joint pain score, DLQI, EQ‐5D utility, and EQ‐5D VAS, respectively, at Week 54. Patients with nail psoriasis had improvements of 51%, 63%, and 24% in NAPSI, DLQI, and EQ‐5D VAS.Conclusion  In this study of moderate‐to‐severe plaque psoriasis, joint and nail symptoms were prevalent and patients with these symptoms had significantly greater HR‐QoL impairment at baseline than unaffected patients. Etanercept provided significant improvement in symptom severity and HR‐QoL.Conflict of InterestT. Luger has acted as a paid consultant to and speaker for Wyeth Pharmaceuticals. J. Barker has acted as a paid consultant to and speaker for, and has received unrestricted research or education support from Wyeth Pharmaceuticals. J. Lambert has acted as a paid consultant to and speaker for Wyeth. S. Yang, D. Robertson, J. Foehl, C. Molta, and R. Boggs are employed by Wyeth Pharmaceuticals, which supported this study financially.
The European Investment Bank: The EU's Neglected Institution*
Authors: ROBINSON NICK 
Published: May 2009

AbstractThe European Investment Bank is the largest multilateral lender in the world, facilitating total spending which is equivalent to the total of the EU budget. Its activity thus has a potentially huge effect on EU policy‐making, yet research to date has failed to recognize this. This article addresses this, offering detailed empirical analysis and re‐evaluating debates on multi‐level governance.
Introduction to the special issue on numerical modeling of hydrothermal fluids
Authors: APPOLD M. S. , NABELEK P. I. 
Published: May 2009

AbstractThis special issue on the numerical modeling of hydrothermal fluids is an outgrowth of a thematic session convened at the 2007 Geological Society of America meeting in Denver. Here we briefly review some of the previous research into numerical modeling of hydrothermal fluids and summarize the contributions in this special issue. We find that despite decades of progress, there is still great untapped potential for providing insights into the behavior of hydrothermal fluids by numerical modeling.
Differential protein expression in the corpus callosum (body) of human alcoholic brain
Authors: Kashem Mohammed Abul , Etages Huyghues Des , Kopitar‐Jerala Nataša , McGregor Iain S. , Matsumoto Izuru 
Published: May 2009

AbstractNeuroimage analysis in alcoholic corpus callosum (CC) suggests that microstructural abnormalities are higher in the genu followed by the body and the splenium. Molecular mechanisms underlying these dysmorphologys are still unclear. Protein expression was performed using the CC body samples [(nine controls, seven uncomplicated, and six complicated (with liver cirrhosis) alcoholics] through proteomics approach. Thirty‐nine protein spots in uncomplicated and 60 in complicated alcoholics were differentially altered compared with the control (p < 0.05). Comparison between alcoholic groups revealed that 40% more protein showed altered expression in complicated compared with uncomplicated. This result suggests that alcohol‐related liver dysfunction has synergetic effects on brain protein expression. Subregional expression profiles indicate that the highest numbers of region‐specific proteins were in the genus followed by the CC body and the splenium. Interestingly, abnormal thiamine cascade was strongly suggested in the genu, and to a lesser extent in the CC body, but no such cascade was observed in the splenium. Therefore, alcohol‐induced microstructural damage detected by image analysis in the CC, possibly involves multiple biochemical mechanisms.
Involvement of multiple protein kinases in cPLA2 phosphorylation, arachidonic acid release, and cell death in in vivo and in vitro models of 1‐methyl‐4‐phenylpyridinium‐induced parkinsonism – the possible key role of PKG
Authors: Chalimoniuk Malgorzata , Stolecka Anna , Ziemińska Elzbieta , Stępień Adam , Langfort Josef , Strosznajder Joanna B. 
Published: May 2009

AbstractThe study was aimed at investigating in vivo and in vitro the involvement of the cGMP/cGMP‐dependent protein kinase (PKG) signaling pathway in MPP+‐induced cytosolic phospholipase A2 (cPLA2) activation of dopaminergic neurons. MPP+ activated neuronal nitric oxide synthase (NOS)/soluble guanylyl cyclase/cGMP pathway in mouse midbrain and striatum, and in pheochromocytoma cell line 12 cells, and caused an upward shift in [Ca2+]i level in the latter. The activation was accompanied by increases in total and phosphorylated cPLA2, and increased arachidonic acid release. Effects of selective inhibitors [2‐oxo‐1,1,1‐trifluoro‐6,9‐12,15‐heneicosatetraene (AACOCF3), (E)‐6‐(bromomethylene)tetrahydro‐3‐(1‐naphthalenyl)2h‐pyran‐2‐one (BEL)] indicated the main impact of cPLA2 on arachidonic acid release in pheochromocytoma cell line 12 cells. Treatment of the cells with the protein kinase inhibitors GF102610x, UO126, and KT5823, and with the nitric oxide synthase (NOS) inhibitor NNLA revealed the involvement of protein kinase C (PKC) and extracellular signal‐regulated kinases 1 and 2 (ERK 1/2), with the possible key role of PKG, in cPLA2 phosphorylation at Ser505. Inhibitors of cPLA2 and PKG increased viability and reduced MPP+‐induced apoptosis of the cells. Our results indicate that the neuronal NOS/cGMP/PKG pathway stimulates cPLA2 phosphorylation at Ser505 by activating PKC and ERK1/2, and suggest that up‐regulation of this pathway in experimental models of Parkinson’s disease may mediate dopaminergic neuron degeneration and death through activation of cPLA2.
Calpain‐mediated activation of NO synthase in human neuroblastoma SK‐N‐BE cells
Authors: Averna Monica , Stifanese Roberto , De Tullio Roberta , Beccaria Francesco , Salamino Franca , Pontremoli Sandro , Melloni Edon 
Published: May 2009

AbstractIn resting human neuronal cells, nitric oxide synthase (nNOS) is present in its native 160 kDa form in a quiescent state predominantly co‐localized on the plasma membrane, via its PDZ (Psd‐95/Discs‐large/Zona Occludens) domain, with NMDA receptor (NMDA‐R) and in tight association with heat shock protein 90 (HSP90). Following exposure of the cells to Ca2+‐ionophore or to NMDA, nNOS undergoes proteolytic removal of the PDZ domain being converted into a fully active 130 kDa form. The newly generated nNO synthase form dissociates from NMDA‐R and extensively diffuses into the cytosol in direct correlation with NO production. Intracellular redistribution and activation of nNOS are completely prevented in cells preloaded with calpain inhibitor‐1, indicating that these processes are triggered by a concomitant activation of calpain. The role of calpain has been confirmed by immunoprecipitation experiments revealing that also μ‐calpain is specifically recruited into the NMDA‐R‐nNOS‐HSP90 complex following calcium loading. Thus, the formation of clusters containing HSP90, μ‐calpain, nNOS and NMDA‐R represents the limiting step for the operation of the mechanism that links an efficient synthesis of NO to a local increase in Ca2+ influx.
On the mechanism of internalization of α‐synuclein into microglia: roles of ganglioside GM1 and lipid raft
Authors: Park Ji‐Young , Kim Kwang Soo , Lee Saet‐Byul , Ryu Jae‐Sung , Chung Kwang Chul , Choo Young‐Kug , Jou Ilo , Kim Jongsun , Park Sang Myun 
Published: May 2009

Abstractα‐Synuclein (α‐syn) has been known to be a key player of the pathogenesis of Parkinson’s disease and has recently been detected in extracellular biological fluids and shown to be rapidly secreted from cells. The penetration of α‐syn into cells has also been observed. In this study, we observed that dl‐threo‐1‐phenyl‐2‐decanoylamino‐3‐morpholino‐1‐propanol, a glucosyltransferase inhibitor, and proteinase K inhibited the internalization of extracellular monomeric α‐syn into BV‐2 cells, and the addition of monosialoganglioside GM1 ameliorated the inhibition of α‐syn internalization in dl‐threo‐1‐phenyl‐2‐decanoylamino‐3‐morpholino‐1‐propanol‐treated BV‐2 cells. Furthermore, inhibition of clathrin‐, caveolae‐, and dynamin‐dependent endocytosis did not prevent the internalization of α‐syn, but disruption of lipid raft inhibited it. Inhibition of macropinocytosis and disruption of actin and microtubule structures also did not inhibit the internalization of α‐syn. In addition, we further confirmed these observations by co‐culture system of BV‐2 cells and α‐syn‐over‐expressing SH‐SY5Y cells. These findings suggest that extracellular α‐syn is internalized into microglia via GM1 as well as hitherto‐unknown protein receptors in clathrin‐, caveolae‐, and dynamin‐independent, but lipid raft‐dependent manner. Elucidation of the mechanism involved in internalization of α‐syn should be greatly helpful in the development of new treatments of α‐syn‐related neurodegenerative diseases.
A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid
Authors: Castro Maite A. , Beltrán Felipe A. , Brauchi Sebastián , Concha Ilona I. 
Published: May 2009

AbstractIn this review, we discuss a novel function of ascorbic acid in brain energetics. It has been proposed that during glutamatergic synaptic activity neurons preferably consume lactate released from glia. The key to this energetic coupling is the metabolic activation that occurs in astrocytes by glutamate and an increase in extracellular [K+]. Neurons are cells well equipped to consume glucose because they express glucose transporters and glycolytic and tricarboxylic acid cycle enzymes. Moreover, neuronal cells express monocarboxylate transporters and lactate dehydrogenase isoenzyme 1, which is inhibited by pyruvate. As glycolysis produces an increase in pyruvate concentration and a decrease in NAD+/NADH, lactate and glucose consumption are not viable at the same time. In this context, we discuss ascorbic acid participation as a metabolic switch modulating neuronal metabolism between rest and activation periods. Ascorbic acid is highly concentrated in CNS. Glutamate stimulates ascorbic acid release from astrocytes. Ascorbic acid entry into neurons and within the cell can inhibit glucose consumption and stimulate lactate transport. For this switch to occur, an ascorbic acid flow is necessary between astrocytes and neurons, which is driven by neural activity and is part of vitamin C recycling. Here, we review the role of glucose and lactate as metabolic substrates and the modulation of neuronal metabolism by ascorbic acid.
The adenosine A2A receptor antagonist ZM241385 enhances neuronal survival after oxygen‐glucose deprivation in rat CA1 hippocampal slices
Authors: Pugliese AM , Traini C , Cipriani S , Gianfriddo M , Mello T , Giovannini MG , Galli A , Pedata F 
Published: May 2009

Background and purpose:  Activation of adenosine A2A receptors in the CA1 region of rat hippocampal slices during oxygen‐glucose deprivation (OGD), a model of cerebral ischaemia, was investigated.Experimental approach:  We made extracellular recordings of CA1 field excitatory postsynaptic potentials (fepsps) followed by histochemical and immunohistochemical techniques coupled to Western blots.Key results:  OGD (7 or 30 min duration) elicited an irreversible loss of fepsps invariably followed by the appearance of anoxic depolarization (AD), an unambiguous sign of neuronal damage. The application of the selective adenosine A2A receptor antagonist, ZM241385 (4‐(2‐[7‐amino‐2‐{2‐furyl}{1,2,4}triazolo{2,3‐a}{1,3,5}triazin‐5‐ylamino]ethyl)phenol; 100–500 nmol·L−1) prevented or delayed AD appearance induced by 7 or 30 min OGD and protected from the irreversible fepsp depression elicited by 7 min OGD. Two different selective adenosine A2A receptor antagonists, SCH58261 and SCH442416, were less effective than ZM241385 during 7 min OGD. The extent of CA1 cell injury was assessed 3 h after the end of 7 min OGD by propidium iodide. Substantial CA1 pyramidal neuronal damage occurred in untreated slices, exposed to OGD, whereas injury was significantly prevented by 100 nmol·L−1 ZM241385. Glial fibrillary acid protein (GFAP) immunostaining showed that 3 h after 7 min OGD, astrogliosis was appreciable. Western blot analysis indicated an increase in GFAP 30 kDa fragment which was significantly reduced by treatment with 100 nmol·L−1 ZM241385.Conclusions and implications:  In the CA1 hippocampus, antagonism of A2A adenosine receptors by ZM241385 was protective during OGD (a model of cerebral ischaemia) by delaying AD appearance, decreasing astrocyte activation and improving neuronal survival.
Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents
Authors: Braida Daniela , Capurro Valeria , Zani Alessia , Rubino Tiziana , Viganò Daniela , Parolaro Daniela , Sala Mariaelvina 
Published: May 2009

Background and purpose:  Drugs targeting brain κ‐opioid receptors produce profound alterations in mood. In the present study we investigated the possible anxiolytic‐ and antidepressant‐like effects of the κ‐opioid receptor agonist salvinorin A, the main active ingredient of Salvia divinorum, in rats and mice.Experimental approach:  Experiments were performed on male Sprague‐Dawley rats or male Albino Swiss mice. The anxiolytic‐like effects were tested by using the elevated plus maze, in rats. The antidepressant‐like effect was estimated through the forced swim (rats) and the tail suspension (mice) test. κ‐Opioid receptor involvement was investigated pretreating animals with the κ‐opioid receptor antagonist, nor‐binaltorphimine (1 or 10 mg·kg−1), while direct or indirect activity at CB1 cannabinoid receptors was evaluated with the CB1 cannabinoid receptor antagonist, N‐(piperidin‐1‐yl) ‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide (AM251, 0.5 or 3 mg·kg−1), binding to striatal membranes of naïve rats and assay of fatty acid amide hydrolase in prefrontal cortex, hippocampus and amygdala.Key results:  Salvinorin A, given s.c. (0.001–1000 µg·kg−1), exhibited both anxiolytic‐ and antidepressant‐like effects that were prevented by nor‐binaltorphimine or AM251 (0.5 or 3 mg·kg−1). Salvinorin A reduced fatty acid amide hydrolase activity in amygdala but had very weak affinity for cannabinoid CB1 receptors.Conclusions and implications:  The anxiolytic‐ and antidepressant‐like effects of Salvinorin A are mediated by both κ‐opioid and endocannabinoid systems and may partly explain the subjective symptoms reported by recreational users of S. divinorum.
Resolvin D1 controls inflammation initiated by glutathione‐lipid conjugates formed during oxidative stress
Authors: Spite M , Summers L , Porter TF , Srivastava S , Bhatnagar A , Serhan CN 
Published: May 2009

Background and purpose:  Inflammation is associated with oxidative stress and local generation of lipid peroxidation‐derived aldehydes, such as 4‐hydroxy‐trans‐2‐nonenal (HNE). In most tissues, HNE is readily conjugated with glutathione and presently it is unknown whether glutathionyl‐HNE (GS‐HNE) plays a functional role in inflammation. Here, we sought to determine whether GS‐HNE is a mediator of oxidative stress‐initiated inflammation and if its actions can be regulated by the anti‐inflammatory and pro‐resolving lipid mediator, resolvin D1 (RvD1).Experimental approach:  GS‐HNE was administered intraperitoneally to mice and peritoneal lavages were assessed for leukocyte infiltration and lipid mediators were targeted by mediator‐lipidomics. RvD1 was administered to mice treated with GS‐HNE and leukocyte infiltration was assessed in the peritoneum. Superoxide production and CD11b modulation were measured in isolated human polymorphonuclear leukocytes incubated with GS‐HNE.Key results:  GS‐HNE (1–10 µg) evoked infiltration of Gr‐1+ leukocytes into the peritoneum to form an inflammatory exudate. With isolated human polymorphonuclear leukocytes, GS‐HNE stimulated both superoxide generation and CD11b expression. Among the lipid mediators, both cyclooxygenase‐ and lipoxygenase‐derived pro‐inflammatory eicosanoids, including prostaglandin E2, leukotriene B4 and cysteinyl leukotrienes, were generated in exudates of mice injected intraperitoneally with GS‐HNE. RvD1, given i.v. in doses as low as 0.01–10.0 ng, sharply reduced GS‐HNE‐stimulated leukocyte infiltration (∼30–70%).Conclusions and implications:  Glutathione conjugates of HNE, derived during oxidative stress, are pro‐inflammatory in vivo. RvD1 protects against this oxidative stress‐initiated inflammation.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009
Electroacupuncture Inhibits Ethanol‐Induced Locomotor Sensitization and Alters homer1A mRNA Expression in Mice
Authors: Dos Santos Jr Jair Guilherme , Filev Renato , Coelho Carolina Tesone , Yamamura Ysao , Mello Luiz E. , Tabosa Angela 
Published: May 2009

Background:  Here we investigated the effects of electroacupuncture over locomotor sensitization induced by ethanol in mice.Methods:  Adult male Swiss mice were daily injected with ethanol (2 g/kg, i.p.) or saline for 21 days (acquisition phase). After 4 days of withdrawal, all animals were challenged with ethanol (1.4 g/kg, i.p.). The locomotor activity during 30 minutes was accessed just after the ethanol challenge. Electroacupuncture at acquisition, expression, or maintenance phases of locomotor sensitization was provided over ST‐36 (Zusanli) or PC‐6 (Neiguan) as well as concomitantly over these 2 acupoints. One hour after the challenge with ethanol, the animals were decapitated, the hippocampus, striatum, and prefrontal cortex were dissected, and the expression of homer1A mRNA assessed by PCR.Results:  Electroacupuncture provided simultaneously over ST‐36 and PC‐6 (but not to ST‐36 or PC‐6 alone) inhibited the acquisition, expression, and maintenance of ethanol‐induced locomotor sensitization. In addition, electroacupuncture blocked the diminution of homer1A mRNA expression triggered by ethanol in the acquisition (striatum and prefrontal cortex), expression (hippocampus), and in the maintenance (hippocampus and prefrontal cortex) phases.Conclusion:  Electroacupuncture provided concomitantly over ST‐36 and PC‐6 prevents the sensitization of the mesocorticolimbic pathway induced by ethanol in mice. In addition, these effects were accompanied by changes in the expression of homer1A. We suggest that electroacupuncture effects over ethanol‐induced locomotor sensitization are associated to its ability to modulate homer1A expression and glutamatergic plasticity.
Increased expression of integrin α2 and abnormal response to TGF‐β1 in hereditary gingival fibromatosis
Authors: Zhou J , Meng LY , Ye XQ , Von den Hoff JW , Bian Z 
Published: May 2009

Objective:  To investigate the possible correlation between integrin α1, α2, and β1 expression and excessive collagen synthesis in fibroblasts from 3 unrelated Chinese families with hereditary gingival fibromatosis (HGF).Design:  Gingival fibroblasts from three Chinese HGF patients and three healthy subjects were included. The expression of α1, α2, and β1 integrin subunits was examined by immunohistochemistry, quantitative PCR, and flow cytometry. We also investigated the effects of transforming growth factor‐β1 (TGF‐β1) on the expression of these integrin subunits.Results:  Our results demonstrate that the expression of α2 was significantly higher in HGF fibroblasts compared with control fibroblasts (P < 0.01). No significant differences in the expression of α1 and β1 were detected. Furthermore, TGF‐β1 promoted the expression of α1 and α2 in fibroblasts from both HGF patients and controls. However, it had a larger effect on the expression of α2 in HGF fibroblasts than in control cells. In contrast, α1 expression was stimulated more in control fibroblasts.Conclusion:  The increased expression of integrin α2 and the increased response to TGF‐β1 of HGF fibroblasts may be related to the excessive collagen deposition in HGF patients.
Silage preparation and nutritive value of Chinese yam by‐product
Authors: XU Chuncheng , CAI Yimin , TOYOKAWA Koji 
Published: May 2009

ABSTRACTThe objective of this experiment was to determine the ensiling characteristics, nutrient composition and nutritive value of Chinese yam by‐product (CYBP) silage treated without additive (Control), with lactic acid bacteria (LY), with dried beet pulp (BY), or with mixtures of lactic acid bacteria and dried beet pulp (LBY) for a fermentation period of 150 days. The nutritive value of CYBP silage was studied in an in vivo digestibility trial using wethers in a 4 × 4 Latin square design. Addition of lactic acid bacteria and/or dried beet pulp greatly improved fermentation quality of CYBP silage. The pH was reduced to below 4.0 and lactic acid was produced at above 4.6% on dry matter basis. There were no statistical differences among treatments in the digestibilities of dry matter, organic matter, crude protein and energy in the silages, but neutral detergent fiber and acid detergent fiber digestibility were higher (P < 0.001) in wethers fed BY and LBY silages compared to the control and LY silages. It was estimated that total digestible nutrient and digestible energy in the CYBP silage averaged 79.1% and 14.3 MJ/kg on dry matter basis. The study suggests that CYBP can be well preserved by making a silage and it is a good potential energy source for ruminant diets.