bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute vasodilator effects of Rho-kinase inhibitors in neonatal rats with pulmonary hypertension unresponsive to nitric oxide
Authors: McNamara Patrick J. , Murthy Prashanth , Kantores Crystal , Teixeira Lilian , Engelberts Doreen , van Vliet Todd , Kavanagh Brian P. , Jankov Robert P.
Published: November 2007

Pulmonary hypertension (PHT) in neonates is often refractory to the current best therapy, inhaled nitric oxide (NO). The utility of a new class of pulmonary vasodilators, Rho-kinase (ROCK) inhibitors, has not been examined in neonatal animals. Our objective was to examine the activity and expression of RhoA/ROCK in normal and injured pulmonary arteries and to determine the short-term pulmonary hemodynamic (assessed by pulse wave Doppler) effects of ROCK inhibitors (15 mg/kg ip Y-27632 or 30 mg/kg ip fasudil) in two neonatal rat models of chronic PHT with pulmonary vascular remodeling (chronic hypoxia, 0.13 FiO2, or 1 mg·kg−1·day−1ip chronic bleomycin for 14 days from birth). Activity of the RhoA/ROCK pathway and ROCK expression were increased in hypoxia- and bleomycin-induced PHT. In both models, severe PHT [characterized by raised pulmonary vascular resistance (PVR) and impaired right ventricular (RV) performance] did not respond acutely to inhaled NO (20 ppm for 15 min) or to a single bolus of a NO donor, 3-morpholinosydnonimine hydrochloride (SIN-1; 2 μg/kg ip). In contrast, a single intraperitoneal bolus of either ROCK inhibitor (Y-27632 or fasudil) completely normalized PVR but had no acute effect on RV performance. ROCK-mediated vasoconstriction appears to play a key role in chronic PHT in our two neonatal rat models. Inhibitors of ROCK have potential as a testable therapy in neonates with PHT that is refractory to NO.
Evidence and structural mechanism for late lung alveolarization
Authors: Schittny Johannes C. , Mund Sonja I. , Stampanoni Marco
Published: November 2007

According to the current view, the formation of new alveolar septa from preexisting ones ceases due to the reduction of a double- to a single-layered capillaries network inside the alveolar septa (microvasculature maturation postnatal days 14– 21 in rats). We challenged this view by measuring stereologically the appearance of new alveolar septa and by studying the alveolar capillary network in three-dimensional (3-D) visualizations obtained by high-resolution synchrotron radiation X-ray tomographic microscopy. We observed that new septa are formed at least until young adulthood (rats, days 4– 60) and that roughly half of the new septa are lifted off of mature septa containing single-layered capillary networks. At the basis of newly forming septa, we detected a local duplication of the capillary network. We conclude that new alveoli may be formed in principle at any time and at any location inside the lung parenchyma and that lung development continues into young adulthood. We define two phases during developmental alveolarization. Phase one ( days 4– 21), lifting off of new septa from immature preexisting septa, and phase two ( day 14 through young adulthood), formation of septa from mature preexisting septa. Clinically, our results ask for precautions using drugs influencing structural lung development during both phases of alveolarization.
Tetradecylthioacetic acid prevents the inflammatory response in two-kidney, one-clip hypertension
Authors: Bivol Liliana M. , Berge Rolf K. , Iversen Bjarne M.
Published: November 2007

ANG II promotes inflammation through nuclear factor-κB (NF-κB)-mediated induction of cytokines and reactive oxygen species (ROS). The aim of the present study was to examine the effect of tetradecylthioacetic acid (TTA), a modified fatty acid, on NF-κB, proinflammatory markers, ROS, and nitric oxide (NO) production in two-kidney, one-clip (2K1C) hypertension. The 2K1C TTA-treated group had lower blood pressure (128 ± 3 mmHg) compared with 2K1C nontreated (178 ± 5 mmHg, P < 0.001). The p50 and p65 subunits of NF-κB were higher in the clipped kidney (0.44 ± 0.01 and 0.22 ± 0.01, respectively) compared with controls (0.25 ± 0.03 and 0.12 ± 0.02, respectively, P < 0.001). In the 2K1C TTA-treated group, these values were similar to control levels. The same pattern of response was seen in the nonclipped kidney. In 2K1C hypertension, cytokines plasma were higher than in control: TNF-α was 13.5 ± 2 pg/ml ( P < 0.03), IL-1β was 58.8 ± 10 pg/ml ( P = 0.003), IL-6 was 210 ± 33 pg/ml ( P < 0.001), and monocyte chemoattractant protein-1 was 429 ± 21 pg/ml ( P = 0.04). In the 2K1C TTA-treated group, these values were similar to controls, and the same pattern was seen in the clipped kidney. Clipping increased 8-iso-PGF-2α ( P < 0.01) and decreased NO production ( P < 0.01 vs. control) in the urine. TTA treatment normalized these values. NO production was also lower in clipped and nonclipped kidney ( P < 0.001). After TTA treatment, these values were similar to controls. The results indicate that TTA has a potent anti-inflammatory effect in 2K1C by inhibition of p50/p65 NF-κB subunit activation, reduction of cytokines production and ROS, and enhanced NO production.
Metabolic rhythm abnormalities in mice lacking VIP-VPAC2signaling
Authors: Bechtold David A. , Brown Timothy M. , Luckman Simon M. , Piggins Hugh D.
Published: November 2007

The circadian pacemaker in the suprachiasmatic nuclei (SCN) controls endogenous near 24-h physiological and behavioral rhythms in metabolism, neuroendocrine function, and locomotor activity. Recently, we showed that vasoactive intestinal polypeptide (VIP) and its receptor, VPAC2are critical to the intercellular communication between individual SCN neurons, and appropriate synchronization and phasing of these oscillatory cells. Mice defective in VIP signaling manifest grossly impaired circadian rhythms of SCN neuronal firing activity and are typically unable to maintain rhythmic wheel-running behavior in the absence of external time cues. Here we report that daily rhythms of metabolism and feeding behavior are also overtly altered in these animals. Under diurnal conditions (12:12-h light-dark; LD), metabolic and feeding rhythms are advanced in mice lacking either VIP or VPAC2receptor expression, peaking in the late day, rather than early night, as observed in wild-type mice. When placed in constant light (LL), both VIP-deficient and VPAC2receptor-knockout mice exhibit dampening of metabolic and feeding rhythms, which deteriorate after a few days. In addition, overall metabolic rate is greatly reduced in VPAC2-knockout mice, when compared with wild-type mice, regardless of lighting condition. The advancement of metabolic and feeding rhythms in these mice under LD suggests that these rhythms are less sensitive to masking by light. These results demonstrate that altering SCN function not only affects neuronal and wheel-running activity rhythms but also dramatically impairs temporal regulation of metabolism and feeding.
Genetic inactivation of the laminin α5chain receptor Lu/BCAM leads to kidney and intestinal abnormalities in the mouse
Authors: Rahuel Cécile , Filipe Anne , Ritie Léa , El Nemer Wassim , Patey-Mariaud Natacha , Eladari Dominique , Cartron Jean-Pierre , Simon-Assmann Patricia , Le Van Kim Caroline , Colin Yves
Published: November 2007

Lutheran blood group and basal cell adhesion molecule (Lu/BCAM) has been recognized as a unique receptor for laminin α5chain in human red blood cells and as a coreceptor in epithelial, endothelial, and smooth muscle cells. Because limited information is available regarding the function of this adhesion glycoprotein in vivo, we generated Lu/BCAM-null mice and looked for abnormalities in red blood cells as well as in kidney and intestine, two tissues showing alteration in laminin α5chain-deficient mice. We first showed that, in contrast to humans, wild-type murine red blood cells failed to express Lu/BCAM. Lu/BCAM-null mice were healthy and developed normally. However, although no alteration of the renal function was evidenced, up to 90% of the glomeruli from mutant kidneys exhibited abnormalities characterized by a reduced number of visible capillary lumens and irregular thickening of the glomerular basement membrane. Similarly, intestine analysis of mutant mice revealed smooth muscle coat thickening and disorganization. Because glomerular basement membrane and smooth muscle coat express laminin α5chain and are in contact with cell types expressing Lu/BCAM in wild-type mice, these results provide evidence that Lu/BCAM, as a laminin receptor, is involved in vivo in the maintenance of normal basement membrane organization in the kidney and intestine.
Defining an inhibitory domain in the α-subunit of the epithelial sodium channel
Authors: Carattino Marcelo D. , Passero Christopher J. , Steren Carlos A. , Maarouf Ahmad B. , Pilewski Joseph M. , Myerburg Mike M. , Hughey Rebecca P. , Kleyman Thomas R.
Published: November 2007

Epithelial sodium channels (ENaC) are processed by proteases as they transit the biosynthetic pathway. We recently observed that furin-dependent processing of the α-subunit of ENaC at two sites within its extracellular domain is required for channel activation due to release of a 26-residue inhibitory domain. While channels with α-subunits lacking the furin sites are not cleaved and have very low activity, channels lacking the furin consensus sites as well as the tract between these sites (αD206–R231) are active. We analyzed channels with a series of deletions in the tract αD206–R231 and lacking the α-subunit furin consensus sites in Xenopus laevis oocytes. We found an eight-residue tract that, when deleted, restored channel activity to the level found in oocytes expressing wild-type ENaC. A synthetic peptide, LPHPLQRL, representing the tract αL211–L218, inhibited wild-type ENaC expressed in oocytes with an IC50of 0.9 μM, and inhibited channels expressed in collecting duct cells and human primary airway epithelial cells with an IC50s of between ∼50 and 100 μM. Analyses of peptides with deletions within this inhibitory tract indicate that eight residues is the minimal backbone length that is required for ENaC inhibition. Analyses of 8-mer peptides with conserved and nonconserved substitutions suggest that L1, P2, H3, P4, and L8are required for inhibitory activity. Our findings suggest that this eight-residue tract is a key conserved inhibitory domain that provides epithelial cells with a reserve of inactive channels that can be activated as required by proteases.
Inhibition of tubular cell proliferation by neutralizing endogenous HGF leads to renal hypoxia and bone marrow-derived cell engraftment in acute renal failure
Authors: Ohnishi Hiroyuki , Mizuno Shinya , Nakamura Toshikazu
Published: November 2007

During the progression of acute renal failure (ARF), the renal tubular S3 segment is sensitive to ischemic stresses. For reversing tubular damage, resident tubular cells proliferate, and bone marrow-derived cells (BMDC) can be engrafted into injured tubules. However, how resident epithelium or BMDC are involved in tubular repair remains unknown. Using a mouse model of ARF, we examined whether hepatocyte growth factor (HGF) regulates a balance of resident cell proliferation and BMDC recruitment. Within 48 h post-renal ischemia, tubular destruction became evident, followed by two-waved regenerative events: 1) tubular cell proliferation between 2 and 4 days, along with an increase in blood HGF; and 2) appearance of BMDC in the tubules from 6 days postischemia. When anti-HGF IgG was injected in the earlier stage, tubular cell proliferation was inhibited, leading to an increase in BMDC in renal tubules. Under the HGF-neutralized state, stromal cell-derived factor-1 (SDF1) levels increased in renal tubules, associated with the enhanced hypoxia. Administrations of anti-SDF1 receptor IgG into ARF mice reduced the number of BMDC in interstitium and tubules. Thus possible cascades include 1) inhibition of tubular cell proliferation by neutralizing HGF leads to renal hypoxia and SDF1 upregulation; and 2) BMDC are eventually engrafted in tubules through SDF1-mediated chemotaxis. Inversely, administration of recombinant HGF suppressed the renal hypoxia, SDF1 upregulation, and BMDC engraftment in ARF mice by enhancing resident tubular cell proliferation. Thus we conclude that HGF is a positive regulator for eliciting resident tubular cell proliferation, and SDF1 for BMDC engraftment during the repair process of ARF.
CaR activation increases TNF production by mTAL cells via a Gi-dependent mechanism
Authors: Abdullah Huda Ismail , Pedraza Paulina L. , McGiff John C. , Ferreri Nicholas R.
Published: November 2007

We evaluated the contribution of calcium-sensing receptor (CaR)-mediated Gi-coupled signaling to TNF production in medullary thick ascending limb (mTAL) cells. A selective Giinhibitor, pertussis toxin (PTX), but not the inactive B-oligomer binding subunit, abolished CaR-mediated increases in TNF production. The inhibitory effect of PTX was partially reversed by using an adenylate cyclase inhibitor. CaR-mediated TNF production also was partially reversed by a cAMP analog, 8-Br-cAMP. IP1accumulation was CaR dependent and blocked by PI-PLC; partial inhibition also was observed with PTX. CaR increased calcineurin (CaN) activity by approximately threefold, and PTX prevented CaR-mediated increases in CaN activity, an nuclear factor of activated T cells (NFAT)- cis reporter construct, and a TNF promoter construct. The interaction between Giand PKC was determined, as we previously showed that CaR-mediated TNF production was CaN and NFAT- mediated and Gqdependent. CaR activation increased PKC activity by twofold, an effect abolished by transient transfection with a dominant negative CaR construct, R796W, or pretreatment with PTX. Inhibition with the pan-specific PKC inhibitor GF 109203X (20 nM) abolished CaR-mediated increases in activity of CaN, an NFAT reporter, and a TNF promoter construct. Collectively, the data suggest that Gi-coupled signaling contributes to NFAT-mediated TNF production in a CaN- and PKC-dependent manner and may be part of a CaR mechanism to regulate mTAL function. Moreover, concurrent Gqand Gisignaling is required for CaR-mediated TNF production in mTAL cells via a CaN/NFAT pathway that is PKC dependent. Understanding CaR-mediated signaling pathways that regulate TNF production in the mTAL is crucial to defining novel mechanisms that regulate extracellular fluid volume and salt balance.
A comparison of central aspects of fatigue in submaximal and maximal voluntary contractions
Authors: Taylor Janet L. , Gandevia Simon C.
Published: November 2007

Magnetic and electrical stimulation at different levels of the neuraxis show that supraspinal and spinal factors limit force production in maximal isometric efforts (“central fatigue”). In sustained maximal contractions, motoneurons become less responsive to synaptic input and descending drive becomes suboptimal. Exercise-induced activity in group III and IV muscle afferents acts supraspinally to limit motor cortical output but does not alter motor cortical responses to transcranial magnetic stimulation. “Central” and “peripheral” fatigue develop more slowly during submaximal exercise. In sustained submaximal contractions, central fatigue occurs in brief maximal efforts even with a weak ongoing contraction (<15% maximum). The presence of central fatigue when much of the available motor pathway is not engaged suggests that afferent inputs contribute to reduce voluntary activation. Small-diameter muscle afferents are likely to be activated by local activity even in sustained weak contractions. During such contractions, it is difficult to measure central fatigue, which is best demonstrated in maximal efforts. To show central fatigue in submaximal contractions, changes in motor unit firing and force output need to be characterized simultaneously. Increasing central drive recruits new motor units, but the way this occurs is likely to depend on properties of the motoneurons and the inputs they receive in the task. It is unclear whether such factors impair force production for a set level of descending drive and thus represent central fatigue. The best indication that central fatigue is important during submaximal tasks is the disproportionate increase in subjects' perceived effort when maintaining a low target force.
Adrenalectomy Potentiates Noradrenergic Suppression of GABAergic Transmission in Parvocellular Neurosecretory Neurons of Hypothalamic Paraventricular Nucleus
Authors: Yang Jian Hua , Li Long Hua , Shin Seung Yub , Lee Sora , Lee So Yeong , Han Seong Kyu , Ryu Pan Dong
Published: November 2007

Glucocorticoids are known to regulate both the noradrenergic and GABAergic inputs to the paraventricular nucleus (PVN). However, little is known about the effects of glucocorticoids on the interaction of these two input systems. Here we examined the effects of bilateral adrenalectomy (ADX) on the noradrenergic modulation of GABAergic transmission in the type II PVN neurons labeled with a retrograde dye injected into the pituitary stalk. Noradrenaline either reduced or augmented the frequency of spontaneous inhibitory postsynaptic current (sIPSC) without changing the amplitude and decay time constant. These effects were blocked by α2A- and α1A/1L-adrenoceptor antagonists, respectively. ADX increased the proportion of the neurons showing the noradrenergic reduction and the extent of reduction in the IPSC frequency. The ADX-induced changes were reversed by supplementation of ADX rats with corticosterone (10-mg pellet). ADX also potentiated the noradrenergic reduction in the frequency of miniature IPSC and paired-pulse facilitation of evoked IPSC. BRL 44408 (3 μM), a α2A-adrenoceptor antagonist, blocked the noradrenergic reduction in ADX rats. Corticotropin-releasing hormone and/or vasopressin transcripts were detected in neurons displaying noradrenergic augmentation or reduction of IPSC frequency. ADX enhanced the proportion of neurons expressing corticotropin-releasing hormone. Collectively, the results suggest that depletion of corticosterone by ADX markedly potentiates the noradrenergic suppression of GABAergic transmission mediated by the α2A-adrenoceptors on the GABAergic terminals in the parvocellular neurosecretory PVN neurons. These results may provide a novel synaptic mechanism for the glucocorticoid-induced plasticity in the noradrenergic modulation of neuroendocrine function of the PVN.
Suppression of Oxidant-Induced Glutathione Synthesis by Erythromycin in Human Bronchial Epithelial Cells
Authors: He Zhiyi , Li Bing , Yu Liang , Liu Qicai , Zhong Nanshan , Ran Pixin
Published: November 2007

Background: Macrolide antibiotics have anti-inflammatory effects which are utilized for the treatment of chronic inflammatory airway diseases. Recently, their anti-inflammatory effects have been proposed to be beneficial in patients with chronic obstructive pulmonary disease (COPD). Objectives: Since the molecular mechanisms of anti-inflammatory effects are associated with inhibition of activator protein 1 (AP-1) and nuclear factor (NF)-ĸB, and both are reported to be involved in the expression of γ-glutamylcysteine synthetase (γ-GCS), we set out to determine if these drugs influence the oxidant-antioxidant balance in human bronchial epithelial (HBE) cells. Methods: 16HBE cells were preincubated with erythromycin (EM) at different concentrations and times and then exposed to hydrogen peroxide (0.01 mM). Levels of interleukin (IL)-8 and glutathione (GSH), and activity of γ-GCS and γ-GCS heavy subunit (γ-GCS-HS) protein production were assayed. AP-1 and NF-ĸB binding to the 5′-flanking region of IL-8 and γ-GCS-HS genes was assessed by electrophoretic mobility-shift assay. Results: The increase in IL-8 levels and activity of AP-1 induced by H2O2 were abrogated by preincubation of the cells with EM (5 µg/ml) for 36 h. We also showed that preincubation with EM for 48 h inhibited H2O2-induced GSH levels, γ-GCS activity and expression of γ-GCS-HS, and decreased AP-1 binding to the γ-GCS-HS 5′-flanking region. Conclusions: The confirmation of antioxidants maintaining enzyme suppression by EM raised concerns on whether this drug could disrupt the oxidant/ antioxidant balance during long-term use. These data provide important insights into the treatment of inflammatory lung diseases with macrolide antibiotics.
Activation of Thromboxane Receptor Upregulates Interleukin (IL)-1β–Induced VCAM-1 Expression Through JNK Signaling
Authors: Bayat Hossein , Xu Shanqin , Pimentel David , Cohen Richard A. , Jiang Bingbing
Published: November 2007

Objective—Activation of thromboxane receptors (TPr) is implicated in atherosclerosis and inflammation. This study examined how activation of TPr modulates IL-1β–induced vascular cell adhesion molecule (VCAM)-1 expression in aortic vascular smooth muscle cells (VSMCs).

Methods and Results—In VSMCs, activation of TPr with U46619, a stable thromboxane A2mimetic, alone did not induce VCAM-1 expression, but enhanced that caused by IL-1β. The enhancement of VCAM-1 expression caused by U46619 occurred at the transcriptional level and was inhibited either by SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, or by overexpression of a dominant-negative JNK1, but not by SB203580, a p38 mitogen-activated protein kinase inhibitor. The activation of JNK by U46619 resulted in enhanced phosphorylation and nuclear translocation of c-Jun associated with an enhanced activation of activator protein (AP)-1, which were abolished by SQ29548, a TPr antagonist, or the JNK inhibitor. Treatment of the cells with U46619 alone did not induce NF-κB activation. Furthermore, U46619 enhanced IL-1β–induced THP-1 monocyte binding to VSMCs, which was inhibited by SQ29548 or SP600125.

Conclusion—This study demonstrates that activation of TPr upregulates IL-1β–induced VCAM-1 expression by enhancing the activation of JNK pathway that leads to enhanced AP-1 activation.
Adenosine Receptor–Mediated Adhesion of Endothelial Progenitors to Cardiac Microvascular Endothelial Cells
Authors: Ryzhov Sergey , Solenkova Nataliya V. , Goldstein Anna E. , Lamparter Mathias , Fleenor Todd , Young Pampee P. , Greelish James P. , Byrne John G. , Vaughan Douglas E. , Biaggioni Italo , Hatzopoulos Antonis K. , Feoktistov Igor
Published: November 2007

Intracoronary delivery of endothelial progenitor cells (EPCs) is an emerging concept for the treatment of cardiovascular disease. Enhancement of EPC adhesion to vascular endothelium could improve cell retention within targeted organs. Because extracellular adenosine is elevated at sites of ischemia and stimulates neovascularization, we examined the potential role of adenosine in augmenting EPC retention to cardiac microvascular endothelium. Stimulation of adenosine receptors in murine embryonic EPCs (eEPCs) and cardiac endothelial cells (cECs) rapidly, within minutes, increased eEPC adhesion to cECs under static and flow conditions. Similarly, adhesion of human adult culture-expanded EPCs to human cECs was increased by stimulation of adenosine receptors. Furthermore, adenosine increased eEPC retention in isolated mouse hearts perfused with eEPCs. We determined that eEPCs and cECs preferentially express functional A1and A2Badenosine receptor subtypes, respectively, and that both subtypes are involved in the regulation of eEPC adhesion to cECs. We documented that the interaction between P-selectin and its ligand (P-selectin glycoprotein ligand-1) plays a role in adenosine-dependent eEPC adhesion to cECs and that stimulation of adenosine receptors in cECs induces rapid cell surface expression of P-selectin. Our results suggest a role for adenosine in vasculogenesis and its potential use to stimulate engraftment in cell-based therapies.
Redundant Roles for
Sox7
and
Sox18
in Arteriovenous Specification in Zebrafish
Authors: Herpers Robert , van de Kamp Esther , Duckers Henricus J. , Schulte-Merker Stefan
Published: November 2007

The specification of arteries and veins is an essential process in establishing and maintaining a functional blood vessel system. Incorrect arteriovenous specification disrupts embryonic development but has also been diagnosed in human syndromes such as hypotrichosis–lymphedema–telangiectasia, characterized by defects in blood and lymphatic vessels and associated with mutations in SOX18. Here we characterize the role of
sox7
and
sox18
during zebrafish vasculogenesis.
Sox7
and
sox18
are specifically expressed in the developing vasculature, and simultaneous loss of their function results in a severe loss of the arterial identity of the presumptive aorta which instead expresses venous markers, followed by dramatic arteriovenous shunt formations. Our study identifies members of the Sox family as key factors in specifying arteriovenous identity and will help to better understand hypotrichosis–lymphedema–telangiectasia and other diseases.
Emergency Administration of Abciximab for Treatment of Patients With Acute Ischemic Stroke: Results of an International Phase III Trial
Authors: Adams Harold P. , Effron Mark B. , Torner James , Dávalos Antoni , Frayne Judith , Teal Philip , Leclerc Jacques , Oemar Barry , Padgett Lakshmi , Barnathan Elliot S. , Hacke Werner
Published: November 2007

Background and Purpose—

A previous randomized, placebo-controlled, double-blind study suggested that abciximab may be safe and effective in treatment of acute ischemic stroke. The current phase 3 study was planned to test the relative efficacy and safety of abciximab in patients with acute ischemic stroke with planned treatment within 5 hours since symptoms onset.

Methods—

An international, randomized, placebo-controlled, double-blind phase 3 trial tested intravenous administration of abciximab in 2 study cohorts using stratification variables of time since onset and stroke severity. The planned enrollment was 1800 patients. The primary cohort enrolled those patients who could be treated within 5 hours of onset of stroke. A companion cohort enrolled patients that were treated 5 to 6 hours after stroke as well as a smaller cohort of patients who could be treated within 3 hours of stroke present on awakening. The primary efficacy measure was the dichotomous modified Rankin Scale score at 3 months as adjusted to the baseline severity of stroke among subjects in the primary cohort. The primary safety outcome was the rate of symptomatic or fatal intracranial hemorrhage that occurred within 5 days of stroke.

Results—

The trial was terminated prematurely after 808 patients in all cohorts were enrolled by recommendation of an independent safety and efficacy monitoring board due to an unfavorable benefit-risk profile. At 3 months, approximately 33% of patients assigned placebo (72/218) and 32% of patients assigned abciximab (71/221;
P
=0.944) in the primary cohort were judged to have a favorable response to treatment. The distributions of outcomes on the modified Rankin Scale were similar between the treated and control groups. Within 5 days of enrollment, ≈5.5% of abciximab-treated and 0.5% of placebo-treated patients in the primary cohort had symptomatic or fatal intracranial hemorrhage (
P
=0.002). The trial also did not demonstrate an improvement in outcomes with abciximab among patients in the companion and wake-up cohorts. Although the number of patients was small, an increased rate of hemorrhage was noted within 5 days among patients in the wake-up population who received abciximab (13.6% versus 5% for placebo).

Conclusions—

This trial did not demonstrate either safety or efficacy of intravenous administration of abciximab for the treatment of patients with acute ischemic stroke regardless of end point or population studied. There was an increased rate of symptomatic or fatal intracranial hemorrhage in the primary and wake-up cohorts.
Subtype Activation and Interaction of Protein Kinase C and Mitogen-Activated Protein Kinase Controlling Receptor Expression in Cerebral Arteries and Microvessels After Subarachnoid Hemorrhage
Authors: Ansar Saema , Edvinsson Lars
Published: November 2007

Background and Purpose—

The pathogenesis of cerebral ischemia associated with subarachnoid hemorrhage (SAH) still remains elusive. The aim of this study was to examine the involvement of mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) subtypes in the pathophysiology of cerebral ischemia after SAH in cerebral arteries and microvessels and to examine temporal activation of the kinases. We hypothesize that treatment with a MAPK or PKC inhibitor will prevent the SAH-induced kinase activation in brain vessels.

Methods—

SAH was induced by injecting 250 μL blood into the prechiasmatic cistern in the rat. The activation of different MAPK and PKC isotypes in large circle of Willis cerebral arteries and intracerebral microvessels was examined at 0, 1, 3, 6, 12, 24, and 48 hours after SAH and after intrathecal treatment with PKC or MAPK inhibitor by use of Western blot.

Results—

Among the 8 investigated PKC isoforms, only PKCδ was activated at 1 hour and at 48 hours, whereas PKCα was activated at 48 hours after SAH. For the MAPKs, there was early phosphorylation at 1 hour of extracellular signal-regulated kinase 1/2, whereas c-jun N-terminal kinase and p38 showed enhanced phosphorylation only at 48 hours after SAH. The pattern was identical in large cerebral arteries and in intracerebral microvessels. Treatment with either the PKC (RO-31-7549) or the raf (SB386023-b) inhibitor prevented the kinase activation.

Conclusions—

The results show that specific subtypes of the MAPK and PKC pathways are activated in cerebral arteries after SAH and the PKC and raf inhibitors are able to prevent this activation.
Albumin Therapy Improves Local Vascular Dynamics in a Rat Model of Primary Microvascular Thrombosis
Authors: Nimmagadda Anitha , Park Hee-Pyoung , Prado Ricardo , Ginsberg Myron D.
Published: November 2007

Background and Purpose—

High-dose human albumin is robustly neuroprotective in preclinical ischemia models and is currently in phase III clinical trial for acute ischemic stroke. To explore the hypothesis that albumin’s protective effect is mediated in part by salutary intravascular mechanisms, we assessed microvascular hemodynamics in a model of laser-induced cortical arteriolar thrombosis.

Methods—

The cortical microcirculation of anesthetized, physiologically monitored Sprague-Dawley rats was studied in vivo via a frontoparietal cranial window (intact dura) by two-photon laser-scanning microscopy after plasma-labeling with fluorescein-dextran. Focal thrombosis was produced in 30- to 50-μm cortical arterioles by laser irradiation. Arteriolar flow velocity was measured repeatedly by line-scanning. At 30 minutes post-thrombosis, animals were treated with either human albumin, 2 g/kg, or with saline control.

Results—

Baseline arteriolar flow velocity averaged 3.5±1.8 mm/s and was reduced to 10% to 13% of control values by laser-induced thrombosis, which also led to focal vasodilatation (mean, 49% above baseline diameter). Saline treatment at 30 minutes post-thrombosis failed to influence arteriolar flow velocity, which remained depressed at 10% to 22% of control throughout the subsequent 60- to 90-minute observation period. By contrast, albumin treatment induced a prompt rise in median flow velocity to 38% of control by 10 minutes post-treatment, and to 61% to 67% of control by 50 to 60 minutes.

Conclusions—

High-dose albumin therapy induces a prompt, sustained improvement in microvascular hemodynamics distal to a cortical arteriolar thrombosis; these data support an important intravascular component to albumin’s protective effect in acute cerebral ischemia.
The Cost of Pediatric Stroke Care and Rehabilitation
Authors: Lo Warren , Zamel Khaled , Ponnappa Kavita , Allen Antoni , Chisolm Deena , Tang Monica , Kerlin Bryce , Yeates Keith O.
Published: November 2007

Background and Purpose—

There is little data regarding the cost of pediatric stroke care or the elements that contribute to these costs. We examined costs for poststroke care during the first year after diagnosis and compared these costs with the volume of the cerebral infarct and the level of neurological and functional outcome.

Methods—

We identified 39 children who sustained nontraumatic ischemic or hemorrhagic strokes and confirmed the diagnoses by review of medical and radiology records. Medical costs were tabulated for the year after the diagnosis of stroke. Cerebral infarct volumes were measured from MRI or CT scans. Neurological outcome was assessed by telephone with a modification of the Pediatric Stroke Outcome Measure (PSOM), and functional outcomes were assessed with a standardized quality-of-life measure.

Results—

The median cost for poststroke care during the year after diagnosis was $42 338 for the entire group. The cost for stroke care was higher for hemorrhagic stroke than for ischemic stroke. Cost had a significant positive correlation with neurological impairment. The modified PSOM score positively correlated with impairments of physical, emotional, social, and school function.

Conclusions—

The cost of stroke care may be one measure of stroke severity, with more extensive strokes resulting in greater medical costs. In addition, stroke appears to impair children’s social ability along with their neurological function.
Time-dependent Reduction of Tensile Strength Caused by Interfacial Degradation under Constant Strain Duration in UD-CFRP
Authors: Koyanagi Jun , Hatta Hiroshi , Ogawa Fumio , Kawada Hiroyuki
Published: November 2007

The residual strength in UD-CFRP was measured after being subjected to constant strain. In order to quantify the strength reduction, the time-dependent variation of interfacial stress-transfer capacity in a single-fiber composite specimen was quantitatively studied using micro-Raman spectroscopy. The analysis originally included a decrease of interfacial frictional stress due to a relaxation of interfacial radial stress and a time-dependency of an interfacial debonding propagation criterion, based on the conventional viscoelastic shear-lag model. The residual strength in UD-CFRP after enduring long-term loading was then analyzed using the global load sharing model with the results of variation of the interfacial property.
Microstructure of 3D Braided Preform for Composites with Complex Rectangular Cross-section
Authors: Zhang Wei , Ding Xin , Li Yuling
Published: November 2007

Microstructure of four-step 3D braiding preform with 1 × 1 pattern and complex rectangular cross-sections is studied by means of the control volume method. The complex rectangular configuration refers to the geometrical shape jointed by two or more rectangles together. Following the formation rule of the braiding process, the paths of the carriers are traced, particularly in the joint region where two rectangles join together. According to the formation procedures, three unit cell models, both topological and geometrical, are developed corresponding to the microstructure of the interior, surface, and corner in the joint region. The study shows that, in the joint region, the control volume of the unit cell is a cube in the interior, a hepta-prism in the corner, and a penta-prism in the surface, respectively. In addition, the study is able to demonstrate the difference in the braiding pattern and the spatial orientation of braiding yarns in the unit cells between those in the joint region of a complex rectangle and the corresponding region of a simple rectangle by four-step braiding process.
Hella Nor Cal or Totally So Cal?
Authors: Bucholtz Mary , Bermudez Nancy , Fung Victor , Edwards Lisa , Vargas Rosalva
Published: November 2007

This study provides the first detailed account of perceptual dialectology within California (as well as one of the first accounts of perceptual dialectology within any single state). Quantitative analysis of a map-labeling task carried out in Southern California reveals that California's most salient linguistic boundary is between the northern and southern regions of the state. Whereas studies of the perceptual dialectology of the United States as a whole have focused almost exclusively on regional dialect differences, respondents associated particular regions of California less with distinctive dialects than with differences in language (English versus Spanish), slang use, and social groups. The diverse sociolinguistic situation of California is reflected in the emphasis both on highly salient social groups thought to be stereotypical of California by residents and nonresidents alike (e.g., surfers) and on groups that, though prominent in the cultural landscape of the state, remain largely unrecognized by outsiders (e.g., hicks).
The European Public Sphere and the Social Imaginary of the 'New Europe'
Authors: Lauristin Marju
Published: November 2007

The article explores how enlargement of the European Union has affected the development of the European public sphere. At the initial stage of enlargement, communication between the `old' and `new' democracies was hampered by prejudice and estrangement from the western side and illusionary expectations from the eastern side. Different historical experiences after the Second World War had raised barriers to mutual understanding. While experiences of `building capitalism' brought post-Communist nations closer to the values of the European welfare society, the eastwards enlargement at the same time strengthened the influence of identity politics among the `old' democracies of Europe. As a result, there is now less difference between the `old' and 'new' members of the EU than was expected at the beginning of the enlargement process. The new members of the EU are even more interested in the development of the European public sphere than are many people in the West, because they see in this process their chance to be included in the European communication space as equal members. In order to reach this goal, the process of `horizontal integration' between national public spheres and the development of the common social imaginary of the new Europe is considered to be very important. ■
A Cosmopolitan Temptation
Authors: Schlesinger Philip
Published: November 2007

■ For some, the transnationalization of political action and communicative space in the European Union heralds an emergent cosmopolitan order. Need that be so? There are supranational institutions in the EU as well as transnational political and cultural spaces and cross-border communicative flows. However, the Union's member states remain key controllers of citizenship rights and purveyors of collective identities. And for many purposes they still maintain strongly bounded national public spheres. Because the EU's overall character as a polity remains unresolved, this has consequences for the organization of communicative spaces. The EU is a field of tensions and contradictions that is inescapably rooted in institutional realities. Wishful thinking about cosmopolitanism can get in the way of clear analysis. ■
The European and the Nationalin Communication Research
Authors: Mihelj Sabina
Published: November 2007

■ The article discusses some of the major omissions and simplifications created by established approaches to European communication, in particular the inclination to think of Europeanization primarily, and often exclusively, in relation to things national. It points to the simplistic narrative that sees transnational communication in Europe as a very recent phenomenon, and demonstrates how this narrative glosses over various historical forms of transnational communication in Europe. It then briefly addresses the intellectual roots of this narrative, and argues that they also lead to neglecting the existence of diverse, often competing contemporary forms of Europeanization and transnationalization in public communication. Finally, the article argues that more sustained attention should be paid to subnational patterns of stratification of European communication, particularly those arising along class divisions. ■
The European Public Sphere Does Not Exist (At Least It's Worth Wondering...)
Authors: Baisnée Olivier
Published: November 2007

■ This article argues that most research conducted on the topic of the European public sphere (EPS) has been heavily influenced by a definition of the public sphere that has been historically promoted by the European Union institutions themselves. Communication and, later on, public opinion have been considered by EU pioneers as ways to overcome the limited competences of the European institutions. By doing so, they heavily influenced later theories of the European public sphere by promoting a conception of the latter based on two major assumptions: the EPS relies on the availability of information about the EU in national media and all EU citizens are members of the EPS. This article proposes alternative research paths about the EPS. The EPS should probably not be thought of in terms of the national media of the member states, nor should it be conceived as including all EU citizens. Rather, the EPS appears as sectoral, heavily selective and including actors from various professional and policy areas that have, in common, a strong interest in EU matters. ■
Anti-genotoxic effect of hydrated sodium calcium aluminosilicate on genotoxicity to human lymphocytes induced by aflatoxin B1
Authors: Türkez Hasan , Şişman Turgay
Published: November 2007

The anti-genotoxic potential of hydrated sodium calcium aluminosilicate (HSCAS) was investigated using sister chromatid exchanges (SCEs) induced by aflatoxin B1 (AFB 1) as genotoxic endpoint in human lymphocytes. Whole blood samples from two healthy male donors were used for this experiment and the effects of different concentrations of HSCAS (5 × 10 —6 and 1 × 10—5 M) and AFB1 (1, 5 and 10 μM) were tested. The present results established that the frequencies of SCEs (at doses of 5 and 10 μM except for 1 μM) in lymphocytes were significantly increased by AFB1 compared to controls. When HSCAS was added alone at a molar ratio of 5 × 10—6 and 1 × 10— 5, lymphocytes did not show significant increases in SCE frequencies, but SCE frequencies induced by the various concentrations of AFB1 could be significantly reduced by the presence of HSCAS (at both doses). In fact, HSCAS at 1 × 10—5 M completely inhibited SCE formations caused by AFB1. These results suggest for the first time, that HSCAS can antagonize the ability of AFB1 to cause DNA damage that leads to the formation of SCEs.
pH regulated scavenging activity of beer antioxidants through modified DPPH assay
Authors: Singh Neetu , Sharma Ramesh , Balapure Anil K
Published: November 2007

Antioxidants (AO), known for scavenging free radicals (FR) in their modern role in health and disease have attracted global attention. The hallmark of Gastrointestinal (GI) tract is the diverse pH of buccal (pH 6.85) versus gastric (pH 1—2) versus colonic (pH 7.3) milieu that perhaps determines the absorption and availability of AO in vivo. We have proposed here: 1) a `novel' microtitre-plate-adaptable 1,1-diphenyl-2-picrylhydrazyl (DPPH) based assay for quantifying AO in general; 2) the AO content in locally popular Light (LB, ethanol ~ 5%) and Strong (SB, ethanol < 8%) beer at their native (4.4 and 4.1, respectively) and physiological (7.3) pH employing this `novel' assay system has been studied which indicates that pH is the key organizer of events in regulating the scavenging activity of AO.
Effects of xylene and formaldehyde inhalations on renal oxidative stress and some serum biochemical parameters in rats
Authors: Kum Cavit , Sekkin Selim , Kiral Funda , Akar Ferda
Published: November 2007

In this study, it was aimed to demonstrate the possible renal oxidative stress and some serum biochemical parameters and their alterations caused by the exposure to xylene and formaldehyde (HCHO) in rats. Weighing 150—200 g, 12-week-old, 24 female Sprague-Dawley rats were used. The rats were randomly divided into four groups: Group 1 (control), Group 2 (300-ppm technical xylene), Group 3 (6-ppm HCHO) and Group 4 (150-ppm technical xylene + 3-ppm HCHO). The animals were exposed to gases eight hours per day for six weeks. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, glutathione (GSH) and malondialdehyde (MDA) levels were measured. In addition, serum total protein, albumin, urea and creatinine levels were evaluated. Compared with the control animals, urea levels increased significantly in all groups ( P < 0.001). GSH activities and MDA levels increased in xylene and xylene + HCHO groups ( P < 0.05). No statistically considerable differences were found in SOD, CAT and GSH-Px activities, total protein, albumin and creatinine levels among all groups ( P > 0.05). The present study indicates but not statistically confirms the renal toxicity of the exposures to xylene, HCHO and a mixture of them.
Comparative proteomic analysis on human L-02 liver cells treated with varying concentrations of trichloroethylene
Authors: Jianjun Liu  , Huang Haiyan , Xing Xiumei , Xi Renrong , Zhuang Zhixiong , Yuan Jianhui , Yang Fan , Zhao Jin
Published: November 2007

To determine the differential proteomic expressions in human L-02 liver cells induced by varying concentrations of trichloroethylene (TCE), comparative proteomic analysis was performed on human L-02 liver cells which were treated with varying concentrations of TCE. According to the result of MTT test, we designed four different groups, in which the cells were treated with 0 μM (control group), 3, 10 or 40 μM TCE for 24 h, respectively. Comparative analysis of approximately 800 spots resolved by two-dimensional gel electrophoresis (2DE) in the soluble proteomes of L-02 cells from the four different groups resulted in 10 differential proteins. To identify the differential spots, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) was carried out; if the results from the tool were insufficient, tandem MS (MALDI-TOF-TOF-MS) was then performed. The raw data of peptide mass fingerprints (PMFs) and MS/MS spectra were searched against the IPI human data base for exact matches. Then western blot was employed to verify the result of proteomic analysis, the following result confirmed that the results of proteomic analysis were reliable. These results might provide an insight into the underlying mechanism of TCE intoxication and find biological markers for diagnosis and therapy of TCE-induced diseases.
Worker voice in the context of the re-regulation of employment: employer tactics and statutory union recognition in the UK
Authors: Perrett Robert
Published: November 2007

Since the introduction of the statutory recognition procedure the vast majority of new agreements have been voluntary in nature, yet increasingly employers are using this ambiguous state regulation as a means of avoiding recognition.The legislation allows for the game of voluntarism to be enshrined within the micro level politics and social relationships of work and employment: it crystallizes the culture and history of voluntarism in the regulation itself. It is, in effect, ironic in how it balances change with tradition. It makes the new regulation pliable and difficult to see as a step to a state-led approach.There is a resistant trend to unions generally even if recognition cases may vary in terms of employer orientations.This article focuses on such issues by addressing a broader understanding of regulation through an ethnographic case study analysis.
Labour process and decision-making in factories under workers' self-management: empirical evidence from Argentina
Authors: Atzeni Maurizio , Ghigliani Pablo
Published: November 2007

This article focuses on the process of workers' self-management brought about by a wave of factory occupations, which has taken place in Argentina in the last few years, with the support of preliminary evidence from qualitative fieldwork conducted in four factories.The aim of the article is to explore the dynamics of the decision-making and the re-organization of the labour process in the light of the constraints imposed on self-management by market mediations. The act of occupying a factory gives room to workers' control of the labour process and to a more democratic, collective decision-making, but workers' need to compete in the market reduces the sphere of collective decision, leading to centralization of power and divisions between directive and productive workers, hampering the possibility for workers to enrich their job and avoid self-exploitation.