bluuebunny/crossref_metadata_2025 huggingface dataset:
Fas (CD95) May Mediate Delayed Cell Death in Hippocampal CA1 Sector after Global Cerebral Ischemia
Authors: Jin Kunlin , Graham Steven H. , Mao Xiaoou , Nagayama Tetsuya , Simon Roger P. , Greenberg David A.
Published: November 2003

Cell death–regulatory genes like caspases and bcl-2 family genes are involved in delayed cell death in the CA1 sector of hippocampus after global cerebral ischemia, but little is known about the mechanisms that trigger their expression. The authors found that expression of Fas and Fas-ligand messenger ribonucleic acid and protein was induced in vulnerable CA1 neurons at 24 and 72 hours after global ischemia. Fas-associating protein with a novel death domain (FADD) also was upregulated and immunoprecipitated and co-localized with Fas. Caspase-10 was activated and interacted with FADD protein to an increasing extent as the duration of ischemia increased. Moreover, caspase-10 co-localized with both FADD and caspase-3. These findings suggest that Fas-mediated death signaling may play an important role in signaling hippocampal neuronal death in CA1 after global cerebral ischemia.
Altered Expression of the Neuropeptide-Processing Enzyme Carboxypeptidase E in the Rat Brain after Global Ischemia
Authors: Jin Kunlin , Graham Steven H. , Nagayama Tetsuya , Goldsmith Paul C. , Greenberg David A. , Zhou An , Simon Roger P.
Published: November 2003

Carboxypeptidase E, an exoprotease involved in the processing of bioactive peptides released by a regulated secretory pathway, was identified in a subtractive complementary DNA library derived from an ischemic rat brain by differential screening. In situ hybridization and immunocytochemical analysis showed the presence of carboxypeptidase E messenger RNA and protein in the cerebral cortex, thalamus, striatum, and hippocampus of a healthy rat brain. After 15 minutes of transient global ischemia followed by 8 hours of reperfusion, increased levels of carboxypeptidase E messenger RNA and protein were observed in the hippocampal CA1 and CA3 regions and in the cortex, as detected by Northern and Western blot analyses and in situ hybridization. After extended reperfusion (24 to 72 hours), both carboxypeptidase E messenger RNA and protein levels were decreased. The ischemia-induced changes in carboxypeptidase E expression suggest that this enzyme may play a role in modulating the brain's response to ischemia.
Oxidative and Nonoxidative Metabolism of Excited Neurons and Astrocytes
Authors: Gjedde Albert , Marrett Sean , Vafaee Manouchehr
Published: November 2003

There is evidence that the metabolic responses to afferent and efferent nervous activity are dissociated at sites of neuronal excitation in brain. Whether efferent activity follows afferent activity depends on the responsiveness of postsynaptic neurons, which in turn depends on the summation of excitatory and inhibitory postsynaptic potentials. The afferent activity excites the presynaptic terminals and astrocytes, whereas the efferent activity arises from excitation of the dendrites of projection neurons. Measurements in vivo indicate that primary stimulation, elicited by simple stimuli, gives rise to limited increases of energy metabolism associated with afferent activity. Reports show that a major consequence of afferent activity, in addition to the release of excitatory neurotransmitters from presynaptic terminals and the import of glutamate by astrocytes, is the establishment of rates of blood flow commensurate with increased rates of oxidative energy metabolism associated with efferent activity projecting from the site of activation. Increased flow rates overcome the inherent diffusion limitation of oxygen delivery, while increased rates of glycolysis elevate tissue pyruvate contents, to which oxygen consumption rates are matched. In vivo, neurons in the baseline condition sustain no net import of pyruvate or lactate, and the reported changes of metabolism subserving afferent and efferent activity are additive rather than linked by significant additional transfer of pyruvate or lactate from astrocytes. The dissociation of blood flow changes from efferent activity weakens the identification of functional states by changes of blood flow alone. It raises the possibility that uncoupling of flow from oxidative metabolism occurs at sites of low efferent activity, such that dissociations of flow and glycolysis from oxygen consumption signify imbalances of afferent and efferent activity.
Mild Hypothermia Reduces Apoptosis of Mouse Neurons In vitro Early in the Cascade
Authors: Xu Lijun , Yenari Midori A. , Steinberg Gary K. , Giffard Rona G.
Published: November 2003

Recent experimental work has shown that hypothermia with even small decreases in temperature is broadly neuroprotective, but the mechanism of this protection remains unclear. Although reduction of metabolism could explain protection by deep hypothermia, it does not explain the robust protection found with mild hypothermia. Several reports have suggested that ischemic apoptosis is reduced by hypothermia. The authors examined the effects of hypothermia on neuronal apoptosis using serum deprivation, a well-accepted model that induces neuronal apoptosis. Mild hypothermia (33°C) significantly reduced the number of morphologically apoptotic neurons to less than half the number seen in normothermic culture temperatures (37°C) after 48 hours. They examined the effect of hypothermia on several steps in the cascade. Caspase-3, −8, and −9 activity was significantly increased after 24 hours at 37°C, and was significantly lower in cultures deprived of serum at 33°C. Cytochrome c translocation was reduced by hypothermia. Western blot analysis failed to detect significant changes in Bax, bcl-2, or hsp-70 at early time points, whereas hypothermia significantly reduced cJun N-terminal kinase activation. The authors conclude that small decreases in temperature inhibit apoptosis very early, possibly at the level of the initiation of apoptosis, as suggested by reduced cJun N-terminal kinase activation and before the translocation of cytochrome c, with subsequent prevention of caspase activation.
Unchanged Cerebral Blood Flow and Oxidative Metabolism after Acclimatization to High Altitude
Authors: Møller Kirsten , Paulson Olaf B. , Hornbein Tom F. , Colier Wil N. J. M. , Paulson Anna S. , Roach Robert C. , Holm Søren , Knudsen Gitte Moos
Published: November 2003

The authors investigated the effect of acclimatization to high altitude on cerebral blood flow and oxidative metabolism at rest and during exercise. Nine healthy, native sea-level residents were studied 3 weeks after arrival at Chacaltaya, Bolivia (5,260 m) and after reacclimatization to sea level. Global cerebral blood flow at rest and during exercise on a bicycle ergometer was measured by the Kety-Schmidt technique. Cerebral metabolic rates of oxygen, glucose, and lactate were calculated by the Fick principle. Cerebral function was assessed by a computer-based measurement of reaction time. At high altitude at rest, arterial carbon dioxide tension, oxygen saturation, and oxygen tension were significantly reduced, and arterial oxygen content was increased because of an increase in hemoglobin concentration. Global cerebral blood flow was similar in the four conditions. Cerebral oxygen delivery and cerebral metabolic rates of oxygen and glucose also remained unchanged, whereas cerebral metabolic rates of lactate increased slightly but nonsignificantly at high altitude during exercise compared with high altitude at rest. Reaction time was unchanged. The data indicate that cerebral blood flow and oxidative metabolism are unaltered after high-altitude acclimatization from sea level, despite marked changes in breathing and other organ functions.
Comparison of the Effects of Cyclosporin a on the Metabolism of Perfused Rat Brain Slices during Normoxia and Hypoxia
Authors: Serkova Natalie , Donohoe Paul , Gottschalk Sven , Hainz Carsten , Niemann Claus U. , Bickler Philip E. , Litt Lawrence , Benet Leslie Z. , Leibfritz Dieter , Christians Uwe
Published: November 2003

The authors evaluated and compared the metabolic effects of cyclosporin A in the rat brain during normoxia and hypoxia/reperfusion. Ex vivo31P magnetic resonance spectroscopy experiments based on perfused rat brain slices showed that under normoxic conditions, 500 μg/L cyclosporin A significantly reduced mitochondrial energy metabolism (nucleotide triphosphate, 83 ± 9% of controls; phosphocreatine, 69 ± 9%) by inhibition of the Krebs cycle (glutamate, 77 ± 5%) and oxidative phosphorylation (NAD+, 65 ± 14%) associated with an increased generation of reactive oxygen species (285 ± 78% of control). However, the same cyclosporin A concentration (500 μg/L) was found to be the most efficient concentration to inhibit the hypoxia-induced mitochondrial release of Ca2+in primary rat hippocampal cells with cytosolic Ca2+concentrations not significantly different from normoxic controls. Addition of 500 μg/L cyclosporin A to the perfusion medium protected high-energy phosphate metabolism (nucleotide triphosphate, 11 ± 15% of control vs. 35 ± 9% with 500 μg/L cyclosporin A) and the intracellular pH (6.2 ± 0.1 control vs. 6.6 ± 0.1 with cyclosporin A) in rat brain slices during 30 minutes of hypoxia. Results indicate that cyclosporin A simultaneously decreases and protects cell glucose and energy metabolism. Whether the overall effect was a reduction or protection of cell energy metabolism depended on the concentrations of both oxygen and cyclosporin A in the buffer solution.
Ischemia-Induced Brain Damage Depends on Specific Gap-Junctional Coupling
Authors: Frantseva Marina V. , Kokarovtseva Larisa , Velazquez Jose L. Perez
Published: November 2003

Ischemic brain injury results in neuronal loss and associated neurologic deficits. Although there is some evidence that intercellular communication via gap junctions can spread oxidative cell injury, the possible role of gap-junctional communication in ischemia-induced cell death is the object of debate. Because gap junctions directly connect the cytoplasms of coupled cells, they offer a way to propagate stress signals from cell to cell. The authors investigated the contribution of gap-junctional communication to cell death using an in vitro ischemia model, which was reproduced by submersion of organotypic hippocampal slices into glucose-free deoxygenated medium. The gap-junctional blocker carbenoxolone significantly decreased the spread of cell death, as measured by propidium iodide staining, over a 48-hour period after the ischemic episode. Carbenoxolone ameliorated the hypoxia-induced impairment of the intrinsic neuronal electrophysiologic characteristics, as measured by whole-cell patch clamp recordings. To determine whether specific connexins were involved in the spread of postischemic cell death, the authors partially reduced the synthesis of specific connexins using antisense oligodeoxynucleotides. Simultaneous knockdown of two connexins localized mostly in neurons, connexins 32 and 26, resulted in significant neuroprotection 48 hours after the hypoxic– hypoglycemic episode. Similarly, partial reduction of the predominant glial connexin 43 significantly decreased cell death. These results indicate that gap-junctional communication contributes to the propagation of hypoxic injury and that specific gap junctions could be a novel target to reduce brain damage.
Immunohistochemical Localization of Calcitonin Receptor–Like Receptor and Receptor Activity–Modifying Proteins in the Human Cerebral Vasculature
Authors: Oliver Kevin R. , Wainwright Anna , Edvinsson Lars , Pickard John D. , Hill Raymond G.
Published: November 2003

Calcitonin gene-related peptide and adrenomedullin belong to a structurally related neuropeptide family and are potent vasodilators expressed in the trigeminovascular system. The molecular identity of receptors for these proteins has only recently been elucidated. Central to functional binding of these neuropeptides is the G-protein–coupled receptor, the calcitonin receptor–like receptor (CRLR), whose cell surface expression and pharmacology is determined by coexpression of a receptor activity-modifying protein (RAMP). CRLR combined with RAMP1 binds calcitonin gene-related peptide with high affinity, whereas CRLR coexpression with RAMP2 or −3 confers high-affinity binding of adrenomedullin. The authors investigated the expression of these receptor components in human cerebral vasculature to further characterize neuropeptide receptor content and the potential functions of these receptors. Localization has been carried out using specific antisera raised against immunogenic peptide sequences that were subsequently applied using modern immunohistochemical techniques and confocal microscopy. The results are the first to show the presence of these receptor component proteins in human middle meningeal, middle cerebral, pial, and superficial temporal vessels, and confirm that both calcitonin gene-related peptide and adrenomedullin receptors may arise from the coassembly of RAMPs with CRLR in these vessel types. These novel data advance the understanding of the molecular function of the trigeminovascular system, its potential role in vascular headache disorders such as migraine, and may lead to possible ways in which future synthetic ligands may be applied to manage these disorders.
Hypothermic Reperfusion after Cardiac Arrest Augments Brain-Derived Neurotrophic Factor Activation
Authors: D'Cruz Brian J. , Fertig Kristofer C. , Filiano Anthony J. , Hicks Shawn D. , DeFranco Donald B. , Callaway Clifton W.
Published: November 2003

Induction of mild hypothermia improves neurologic outcome after global cerebral ischemia. This study measured levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in hippocampal tissue of rats after resuscitation from 8 minutes of normothermic, asphyxial cardiac arrest. After resuscitation, rats were maintained either at normal temperature (37°C) or cooled to mild hypothermia (33°C, beginning 60 minutes after resuscitation). After 12 or 24 hours, neurotrophin levels in hippocampus were measured by immunoblotting. Ischemia and reperfusion increased hippocampal levels of BDNF. Induction of hypothermia during reperfusion potentiated the increase in BDNF after 24 hours, but not after 12 hours. Levels of NGF were not increased by postresuscitation hypothermia. Hypothermia also increased tissue levels and tyrosine phosphorylation of TrkB, the receptor for BDNF. Increased BDNF levels were correlated with activation of the extracellularly regulated kinase (ERK), a downstream element in the signal transduction cascade induced by BDNF. In contrast to the many deleterious processes during ischemia and reperfusion that are inhibited by induced hypothermia, increasing BDNF levels is a potentially restorative process that is augmented. Increased activation of BDNF signaling is a possible mechanism by which mild hypothermia is able to reduce the neuronal damage typically occurring after cardiac arrest.
Origin of Negative Blood Oxygenation Level—Dependent fMRI Signals
Authors: Harel Noam , Lee Sang-Pil , Nagaoka Tsukasa , Kim Dae-Shik , Kim Seong-Gi
Published: November 2003

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in spike activity are accompanied by modulation in the blood oxygenation level—dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed and are thought to reflect a decrease in neural activity. In this study, the source of the negative BOLD signal was investigated using T2*-weighted BOLD and cerebral blood volume (CBV) techniques in isoflurane-anesthetized cats. A positive BOLD signal change was observed in the primary visual cortex (area 18) during visual stimulation, while a prolonged negative BOLD change was detected in the adjacent suprasylvian gyrus containing higher-order visual areas. However, in both regions neurons are known to increase spike activity during visual stimulation. The positive and negative BOLD amplitudes obtained at six spatial-frequency stimuli were highly correlated, and negative BOLD percent changes were approximately one third of the postitive changes. Area 18 with positive BOLD signals experienced an increase in CBV, while regions exhibiting the prolonged negative BOLD signal underwent a decrease in CBV. The CBV changes in area 18 were faster than the BOLD signals from the same corresponding region and the CBV changes in the suprasylvian gyrus. The results support the notion that reallocation of cortical blood resources could overcome a local demand for increased cerebral blood flow induced by increased neural activity. The findings of this study imply that caution should be taken when interpreting the negative BOLD signals as a decrease in neuronal activity.
The Media Glorifying Burns: A Hindrance to Burn Prevention
Authors: Greenhalgh David G. , Palmieri Tina L.
Published: November 2003

The media have a profound influence on the actions of children and adults. Burns and burn prevention tend to be ignored or even mocked. The purpose of this presentation is to reveal the callousness of the media in its dealings with burns and burn prevention. Printed materials with a relationship to burns, risk of burning, or disrespect for the consequences of burns were collected. The materials were tabulated into four categories: comics, advertisements (ads), articles that made light of burns, and television shows that portrayed behavior that would risk burn injury. Most burn-related materials were found in comics or advertisements. Several comics made light of high-risk behavior with flames, scald injury, contact injury, or burns. In addition, several advertisements showed people on fire or actions that could easily lead to burns. Several articles and televisions shows portrayed high-risk behavior that, in some instances, led to copycat injuries. Flames are frequently used to sell items that target adolescent boys or young men. The high incidence injuries that frequent this population parallel the high-risk behaviors portrayed by the media. The media portrays flames and high-risk behavior for burn injury as being cool, funny, and without consequence. The use of flames on clothing and recreational equipment (skateboards, hot rods) particularly targets the high-risk adolescent male. The burn community should make the media aware of the harm it causes with its callous depiction and glorification of burns.
Change of Complement System Predicts the Outcome of Patients With Severe Thermal Injury
Authors: Kang H. J. , Kim J. H. , Lee E. H. , Lee Y. K. , Hur M. , Lee K. M.
Published: November 2003

To establish the clinical relevance of the changes in the complement system in patients with thermal injury, we studied 20 patients who had third-degree burns on more than 60% of total body surface area. Their levels of the C3, C4, soluble C5b-9, and functional hemolytic activities of total (CH50) and alternative (AH50) complement pathways were sequentially measured for 2 weeks after thermal injury. All patients showed low C3 levels initially but increased C3 levels in the following days. The increasing trend of C3 levels was prominent in survivors but transient and diminished in nonsurvivors. The change of levels of C3, CH50, and AH50 was closely associated with one another, and their chronological trends related to the survival of patients (P = .0060, .0064 and .0066, respectively). The recovery of C3, AH50, and CH50 to normal or supranormal level during the early treatment period relates to the survival of patients with thermal injury. The failure of recovery of the complement system indicates a poor prognosis for patients and the monitoring of complement system might be beneficial in the care of patients with thermal injury.
The Rehabilitation/School Matrix: A Model for Accommodating the Noncompliant Child With Severe Burns
Authors: Pidcock F. S. , Fauerbach J. A. , Ober M. , Carney J.
Published: November 2003

Some children with severe burns may have difficulty following therapeutic recommendations after discharge from a burn center. Noncompliance may result in complications that affect function, surgical management, community reintegration, and successful reentry into school. We present a case study in which a child with significant compliance issues was managed in a coordinated interdisciplinary model. This model extended from acute recovery through reintegration into the classroom. A behavior-modification program was implemented across different levels of care. Educational reentry was facilitated by including a transitional period in a special-needs classroom in a freestanding special-needs school. Requirements for using educational resources to which some children are legally entitled are reviewed. Rehabilitation services that interface with the educational system for children with burns may improve outcomes as these children reintegrate into the community.
Occupational Therapy and Physiotherapy for the Patient with Burns: Principles and Management Guidelines
Authors: Simons M. , King S. , Edgar D.
Published: November 2003

Clinical practice guidelines are a tool to assist with clinical decision making. They provide information about the care for a condition and make recommendations based on research evidence, which can be adapted locally. A focus group within the Allied Health Interest Group of the Australian and New Zealand Burn Association has compiled the “Occupational Therapy and Physiotherapy for the Patient with Burns—Principles and Management Guidelines.” These guidelines are designed as a practical guide to the relevant clinical knowledge and therapy intervention techniques required for effective patient management. Content areas include respiratory management, edema management, splinting and positioning, physical function (mobility, function, exercise), scar management, and psychosocial and mutual elements. The document has undergone extensive review by members of the Australian and New Zealand Burn Association to ensure clarity, internal consistency, and acceptability. The guidelines have been endorsed by the Australian and New Zealand Burn Association. An abridged version of the guidelines is included in this article, with the full document available from www.anzba.org.au.
Contribution of the Heme Oxygenase Pathway to the Maintenance of the Hypothalamic Blood Flow during Diminished Nitric Oxide Synthesis
Authors: Horváth Béla , Hrabák András , Káldi Krisztina , Sándor Péter , Benyó Zoltán
Published: November 2003

The cerebrovascular effects of the heme oxygenase–carbon monoxide pathway were studied in the rat hypothalamus. Intraperitoneal administration of the heme oxygenase inhibitor zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG, 45 μmol/kg) had no significant effect on the resting cerebral blood flow, but increased hypothalamic nitric oxide synthase activity by 67% without changing the CSF cyclic GMP concentration. After pharmacologic inhibition of nitric oxide synthase, the diminished cerebral blood flow was further reduced by 22% after administration of ZnDPBG, and the effect showed direct correlation with the baseline perfusion level. Therefore, endogenous carbon monoxide may significantly contribute to the cerebral vasoregulation under resting conditions and in pathophysiologic states associated with diminished nitric oxide synthesis.
Reorganization of Visual Cortical Maps after Focal Ischemic Lesions
Authors: Zepeda Angelica , Vaca Luis , Arias Clorinda , Sengpiel Frank
Published: November 2003

Plasticity after central lesions may result in the reorganization of cortical representations of the sensory input. Visual cortex reorganization has been extensively studied after peripheral (retinal) lesions, but focal cortical lesions have received less attention. In this study, we investigated the organization of retinotopic and orientation preference maps at different time points after a focal ischemic lesion in the primary visual cortex (V1). We induced a focal photochemical lesion in V1 of kittens and assessed, through optical imaging of intrinsic signals, the functional cortical layout immediately afterwards and at 4, 13, 33, and 40 days after lesion. We analyzed histologic sections and evaluated temporal changes of functional maps. Histological analysis showed a clear lesion at all time points, which shrank over time. Imaging results showed that the retinotopic and orientation preference maps reorganize to some extent after the lesion. Near the lesion, the cortical retinotopic representation of one degree of visual space expands over time, while at the same time the area of some orientation domains also increases. These results show that different cortical representations can reorganize after a lesion process and suggest a mechanism through which filling-in of a cortical scotoma can occur in cortically damaged patients.
Linearized Reference Tissue Parametric Imaging Methods: Application to [11C]DASB Positron Emission Tomography Studies of the Serotonin Transporter in Human Brain
Authors: Ichise Masanori , Liow Jeih-San , Lu Jian-Qiang , Takano Akihiro , Model Kendra , Toyama Hiroshi , Suhara Tetsuya , Suzuki Kazutoshi , Innis Robert B. , Carson Richard E.
Published: November 2003

The authors developed and applied two new linearized reference tissue models for parametric images of binding potential ( BP) and relative delivery ( R1) for [11C]DASB positron emission tomography imaging of serotonin transporters in human brain. The original multilinear reference tissue model (MRTMO) was modified (MRTM) and used to estimate a clearance rate ( k′2) from the cerebellum (reference). Then, the number of parameters was reduced from three (MRTM) to two (MRTM2) by fixing k′2. The resulting BP and R1 estimates were compared with the corresponding nonlinear reference tissue models, SRTM and SRTM2, and one-tissue kinetic analysis (1TKA), for simulated and actual [11C]DASB data. MRTM gave k′2 estimates with little bias (<1%) and small variability (<6%). MRTM2 was effectively identical to SRTM2 and 1TKA, reducing BP bias markedly over MRTMO from 12–70% to 1–4% at the expense of somewhat increased variability. MRTM2 substantially reduced BP variability by a factor of two or three over MRTM or SRTM. MRTM2, SRTM2, and 1TKA had R1 bias <0.3% and variability at least a factor of two lower than MRTM or SRTM. MRTM2 allowed rapid generation of parametric images with the noise reductions consistent with the simulations. Rapid parametric imaging by MRTM2 should be a useful method for human [11C]DASB positron emission tomography studies.
Reduction of Ischemic Brain Damage by Nitrous Oxide and Xenon
Authors: David Helene N , Leveille Frederic , Chazalviel Laurent , MacKenzie Eric T , Buisson Alain , Lemaire Marc , Abraini Jacques H
Published: November 2003

Neuronal death after ischemia-induced brain damage depends largely upon the activation of the N-methyl-D-aspartate (NMDA) excitatory glutamate receptor that is a target for many putative neuroprotective agents. Whereas the NMDA receptors mediate ischemic brain damage, blocking them is deleterious in humans. Here, the authors investigated whether nitrous oxide or xenon, which are gaseous anesthetics with a remarkably safe clinical profile that have been recently demonstrated as effective inhibitors of the NMDA receptor, may reduce the following: (1) ischemia-induced brain damage in vivo, when given after occlusion of the middle cerebral artery (MCAO), a condition needed to make these potentially neuroprotective agents therapeutically valuable; or (2) NMDA-induced Ca2+ influx in cortical cell cultures, a major critical event involved in excitotoxic neuronal death. The authors have shown that both nitrous oxide at 75 vol% and xenon at 50 vol% reduce ischemic neuronal death in the cortex by 70% and further decrease NMDA-induced Ca2+ influx by 30%. In addition, xenon at 50%, but not nitrous oxide at 75 vol%, further decreases ischemic brain damage in the striatum (a subcortical structure that is known to be resistant to neuroprotective interventions). However, at a higher concentration (75 vol%), xenon exhibits potentially neurotoxic effects. The mechanisms of the neuroprotective and potentially neurotoxic effects of nitrous oxide and xenon, as well as the possible therapeutic implications in humans, are discussed.
Cerebrovascular Vasodilation to Extraluminal Acidosis Occurs via Combined Activation of ATP-Sensitive and Ca2+-Activated Potassium Channels
Authors: Lindauer Ute , Vogt Johannes , Schuh-Hofer Sigrid , Dreier Jens P , Dirnagl Ulrich
Published: November 2003

Albeit controversely discussed, it has been suggested by several authors that nitric oxide (NO) serves as a permissive factor in the cerebral blood flow response to systemic hypercapnia. Potassium channels are important regulators of cerebrovascular tone and may be modulated by a basal perivascular NO level. To elucidate the functional targets of the proposed NO modulation during hypercapnia-induced vasodilation, the authors performed experiments in isolated, cannulated, and pressurized rat middle cerebral arteries (MCA). Extracellular pH was reduced from 7.4 to 7.0 in the extraluminal bath to induce NO dependent vasdilation. Acidosis increased vessel diameter by 35 ± 10%. In separate experiments, ATP-sensitive potassium channels (KATP) were blocked by extraluminal application of glibenclamide (Glib), Ca2+-activated potassium channels (KCa) by tetraethylammonium (TEA), voltage-gated potassium channels (Kv) by 4-aminopyridine, and inward rectifier potassium channels (KIR) by BaCl2. Na+-K+-ATP-ase was inhibited by ouabain. Application of TEA slightly constricted the arteries at pH 7.4 and slightly but significantly attenuated the vasodilation to acidosis. Inhibition of the other potassium channels or Na+-K+-ATP-ase had no effect. Combined blockade of KATP and KCa channels further reduced resting diameter, and abolished acidosis induced vasodilation. The authors conclude that mainly KCa channels are active under resting conditions. KATP and KCa channels are responsible for vasodilation to acidosis. Activity of one of these potassium channel families is sufficient for vasodilation to acidosis, and only combined inhibition completely abolishes vasodilation. During NO synthase inhibition, dilation to the KATP channel opener pinacidil or the KCa channel opener NS1619 was attenuated or abolished, respectively. The authors suggest that a basal perivascular NO level is necessary for physiologic KATP and KCa channel function in rat MCA. Future studies have to elucidate whether this NO dependent effect on KATP and KCa channel function is a principle mechanism of NO induced modulation of cerebrovascular reactivity and whether the variability of findings in the literature concerning a modulatory role of NO can be explained by different levels of vascular NO/cGMP concentrations within the cerebrovascular tree.
Oxidative Damage to the Endoplasmic Reticulum is Implicated in Ischemic Neuronal Cell Death
Authors: Hayashi Takeshi , Saito Atsushi , Okuno Shuzo , Ferrand-Drake Michel , Dodd Robert L , Nishi Tatsuro , Maier Carolina M , Kinouchi Hiroyuki , Chan Pak H
Published: November 2003

The endoplasmic reticulum (ER), which plays important roles in apoptosis, is susceptible to oxidative stress. Because reactive oxygen species (ROS) are robustly produced in the ischemic brain, ER damage by ROS may be implicated in ischemic neuronal cell death. We induced global brain ischemia on wild-type and copper/zinc superoxide dismutase (SOD1) transgenic rats and compared ER stress and neuronal damage. Phosphorylated forms of eukaryotic initiation factor 2α (eIF2α) and RNA-dependent protein kinase-like ER eIF2α kinase (PERK), both of which play active roles in apoptosis, were increased in hippocampal CA1 neurons after ischemia but to a lesser degree in the transgenic animals. This finding, together with the finding that the transgenic animals showed decreased neuronal degeneration, indicates that oxidative ER damage is involved in ischemic neuronal cell death. To elucidate the mechanisms of ER damage by ROS, we analyzed glucose-regulated protein 78 (GRP78) binding with PERK and oxidative ER protein modification. The proteins were oxidatively modified and stagnated in the ER lumen, and GRP78 was detached from PERK by ischemia, all of which were attenuated by SOD1 overexpression. We propose that ROS attack and modify ER proteins and elicit ER stress response, which results in neuronal cell death.
Advanced Glycation Endproducts Induce Changes in Glucose Consumption, Lactate Production, and ATP Levels in SH-SY5Y Neuroblastoma Cells by a Redox-Sensitive Mechanism
Authors: de Arriba Susana Garcia , Loske Claudia , Meiners Ina , Fleischer Gerd , Lobisch Michael , Wessel Klaus , Tritschler Hans , Schinzel Reinhard , Münch Gerald
Published: November 2003

Advanced glycation endproducts (AGEs) accumulate on long-lived proteins, including β-amyloid plaques in Alzheimer's disease, and are suggested to contribute to neuronal dysfunction and cell death. We have investigated the effects of a model AGE upon glucose metabolism and energy production in a neuroblastoma cell line. AGEs decrease cellular ATP levels and increase glucose consumption and lactate production. All of the AGE-induced metabolic changes can be attenuated by antioxidants such as (R+)-α-lipoic acid and 17β-estradiol. These antioxidants may become useful drugs against (AGE-mediated) effects in neurodegeneration through their positive effects on cellular energy metabolism.
Management musings 14: we all need approval – even bosses
Authors: Line Maurice B.
Published: November 2003

Looks at how bosses seek approval. Suggests that this is done through staff, or self approval. Concludes that bosses have to accept life without expectation of external approval, and above all not seek it or delude themselves that they have it.
Performance measurement in the Australian on‐line securities marketplace
Authors: Dubelaar Chris , Tsarenko Yelena , Gabbott Mark
Published: November 2003

This study examines performance measurement in on‐line securities companies in the Australian marketplace. Marketing managers of seven on‐line stock brokerage companies in Australian capital cities were interviewed and their on‐line strategies and approaches were systematically reviewed and analysed. The findings suggest that only four of the seven companies were able to articulate a core value proposition and that only two companies used performance measurement in strategic decision‐making about the on‐line component of their businesses. None of the firms was able to draw a direct connection between the performance measures implemented and the value proposition they claimed to offer to their customers. These findings have important implications for both practitioners and academics as they indicate a substantial deficiency in both the theory and practice of on‐line performance measurement. Avenues for further research in the area of on‐line performance measurement are suggested.
Coping with hypercompetition in the financial services industry in Thailand: environmental scanning practices of leaders and followers
Authors: Ngamkroeckjoti Chittipa , Johri Lalit M.
Published: November 2003

The research on medium‐sized finance companies in Thailand shows that companies with well‐organized and managed environmental scanning practices are recovering from the impact of the 1997 financial crisis and are able to respond to the hypercompetitive market context. The industry leaders and followers show two distinct approaches in responding to business environment. The industry leaders focus on short‐ and long‐term horizons, look at a broader set of factors, are able to influence and better foresee changes in the environment and respond towards these movements more pragmatically. The industry followers are slow in capturing changes in the business environment, do not influence industry regulations and can only comply once the policies are handed out by the regulators. The leaders have managed to overcome the debt burden and are looking forward. The followers have to devote attention to cleaning up the past.
The use of EDI for interorganisational co‐operation and co‐ordination in the supply chain
Authors: Martínez Sánchez Angel , Pérez Pérez Manuela
Published: November 2003

This article analyses the moderation effect of co‐operation on electronic data interchange (EDI) adoption, and the influence of EDI use on the co‐ordinating activities in the automotive supply chain. The empirical results from a survey of 116 Spanish automotive suppliers indicate that EDI adopters perceive more operational benefits, more external pressure and mutual understanding, and fewer technical and organisational difficulties than do non‐adopters of EDI. The use of EDI is greater among suppliers that perceive more strategic benefits and fewer cost and organisational difficulties, have a proactive management, are less dependence on suppliers, and adopt EDI earlier. Co‐operation is a moderator of organisational difficulties for EDI adoption and use, and strategic benefits for the use of EDI. The results also show that companies use EDI to become more co‐ordinated with suppliers and customers.
Improving manufacturers’ distribution performance and customer service in grocery products supply in Brazil: a longitudinal study
Authors: Figueiredo Kleber , Arkader Rebecca , Lavalle Cesar , Fernanda Hijjar Maria
Published: November 2003

This article deals with the evolution of customer service practices in grocery products distribution in Brazil (1994‐2001), based on a longitudinal survey of grocery retailers. Data were collected on retailers’ expectations on four relevant dimensions of customer logistics service provided by manufacturers, as well as on their perceptions of logistics service performance of the typical supplier and the best supplier. The evolution of the gaps between retailers’ expectations and manufacturers’ perceived distribution performance was investigated, as well as a trend in terms of an increase or decrease in customer satisfaction with service provided by suppliers in such dimensions. Results indicate that retailers typically tend to be satisfied with the service provided by their suppliers. In addition, there may be an adjustment of distribution performance to expectations of retailers and to the provision, in some cases, of service above customer expectations.
The TQM trajectories in research and development: two Italian cases
Authors: Petroni Giorgio , Ivo Dormio Alberto , Nosella Anna , Verbano Chiara
Published: November 2003

Total quality management programmes applied to research and development often produce great improvements in productivity because they follow trajectories that are lateral and parallel to the principal thrust which is aimed at client satisfaction. Such improvements are obtained through a better definition of the objectives of research activity, and through organisational overhauls which highlight the contribution to the innovation process made by the marketing, engineering, and production functions, through the adoption of more efficient management systems (programming, control, and management of human resources in particular). These changes are met with strong resistance from researchers and technologists who, during the start‐up phase of such programmes, often refuse to operate in accordance with the internal supplier‐client scheme. Such resistance, which was confirmed by the two Italian case studies presented, can be overcome by the intervention of strong leadership and with the setting up of an intense training programme.
Systematic studies of Festuca (Poaceae) occurring in China compared with taxa in North America
Authors: Chen Xiang , Aiken Susan G , Dallwitz Michael J , Bouchard Patrice
Published: November 2003

Members of the genus Festuca in China were studied from an illustrated database developed using the DELTA (DEscription Language for Taxonomy) software package. The database includes the place of valid publication of scientific names; the location of type specimens when known; whether we have examined the type specimens; synonymy; information on habitat, distribution, subgeneric classification, and taxonomic notes; and approximately 200 images. Five subgenera and 58 species including aggregates are recognized. Six taxa are not assigned to a subgenus at this time. Species descriptions of 400–500 words were generated in Chinese and English and are available on the Internet at http://cdelta.ibcas.ac.cn and as a CD-ROM in English and Chinese from the first author. INTKEY has been used to produce parallel and diagnostic descriptions of 120–130 words for 58 species of the genus Festuca for the Flora of China treatment in English. INTKEY and other DELTA programs were used to assess taxa throughout the database and in a detailed study of 11 flat-leaved taxa that appear to have their centre of diversity in China. The awnless taxa from China that were considered belong to the genus Festuca, not Poa. All the flat-leaved Festuca studied are sufficiently morphologically unique to be treated as species distinct from any found in North America. Clustering and phylogenetic methodologies were used to assess subgeneric and sectional classifications. A new section is proposed, Parviglumae sect. nov.Key words: Festuca, Subulatae, DELTA, China, systematics.
Wide-rim functionalization of calix[4]arene: The di- and tetraisocyanocalix[4]arene assembling ligands and their silver(I) polymers and oligomers
Authors: Mongrain Pascal , Harvey Pierre D
Published: November 2003

The 5,11- and 5,17-diisocyano-25,26,27,28-tetra-n-propoxycalix[4]arene bridging ligands (calix(NC)2) have been prepared in four steps with 34 and 30% global yields, respectively. Their corresponding Ag(I) complexes have been prepared from the direct reaction of the ligand with AgBF4 and are characterized from various spectroscopic and physical techniques. The MALDI-TOF spectra indicate the presence of polymers or oligomers of the type {Ag(calix(NC)2)(BF4)}n. The compounds have been characterized further from TGA, DSC, and XRD and compared with the oligomeric species 5,11,17,23-tetraisocyano-25,26,27,28-tetra-n-propoxycalix[4]arene silver(I) (as a BF4 salt).Key words: silver, calix[4]arene, polymer, isocyanide, photosensitive, thermal gravimetric analysis.
Cadmium complexes of the tripodal [Te(N-t-Bu)3]2 dianion and the HgCl2 adduct of a tellurium diimide dimer
Authors: Chivers Tristram , Schatte Gabriele
Published: November 2003

The reactions of CdCl2 or HgCl2 with {Li2[Te(N-t-Bu)3]}2 in n-hexaneTHF give rise to two distinctly different types of product. In the former case the complexes [Li(THF)x][(CdCl)3{Te(N-t-Bu)3}2] (7a (x = 4), 7b (x = 3)) are obtained. The tetrasolvated complex 7a is a solvent-separated ion pair. The trisolvated complex 7b is a contact ion pair in which the fourth coordination site at the Li+ centre is occupied by one of the Cl ligands of the anion. The polycyclic anion in 7a and 7b is comprised of two tripodal [Te(N-t-Bu)3]2 dianions that exhibit different coordination modes to the three CdCl+ units. One ligand is N,N′-chelated to all three metal centres, and each nitrogen atom bridges two Cd atoms, whereas the other is bonded in a tris-N-monodentate fashion in 7b. In 7a there is an additional weak Cd-N interaction. The reaction of HgCl2 with {Li2[Te(N-t-Bu)3]}2 produces the adduct [t-BuNTe(µ-N-t-Bu)2TeN-t-Bu]HgCl2 (8), in which the dimeric tellurium diimide ligand in its cis(exo,exo) configuration is N,N′-chelated to mercury. Polymeric strands parallel to the b axis are formed by weak TeCl interactions (3.5248(16) Å, 3.5876(15) Å) involving both Cl atoms, but only one Te atom of the ligand. Key words: imido ligands, cadmium, mercury, tellurium.
Leptin Promotes Vascular Remodeling and Neointimal Growth in Mice
Authors: Schäfer Katrin , Halle Martin , Goeschen Colin , Dellas Claudia , Pynn Marianne , Loskutoff David J. , Konstantinides Stavros
Published: November 2003

Objectives—

Human obesity is associated with elevated leptin levels and a high risk of death from cardiovascular disease. In the present study, we investigated the effects of leptin on vascular wound healing and arterial lesion growth in mice.

Methods and Results—

Wild-type mice placed on an atherogenic, high-fat diet had elevated (9-fold) leptin levels compared with their counterparts maintained on normal chow, and the former demonstrated significantly enhanced neointimal thickening after carotid artery injury with ferric chloride. The lesions forming in response to injury strongly expressed leptin receptor mRNA and protein. Unexpectedly, the atherogenic diet had no effect on injured vessels from leptin-deficient
ob/ob
mice despite aggravating obesity, diabetes, and hyperlipidemia in these animals. Daily administration of leptin to
ob/ob
mice during the 3-week period after injury reversed this phenotype, dramatically increasing neointimal thickness and the severity of luminal stenosis. Exogenous leptin also enhanced lesion growth and increased cellular proliferation in injured arteries from wild-type mice but had no effect on vessels from leptin receptor–deficient
db/db
mice.

Conclusions—

Our results raise the possibility that there might be a direct, leptin receptor-mediated link between the hyperleptinemia in human obesity and the increased risk for cardiovascular complications associated with this condition.
Common Genomic Response in Different Mouse Models of β-Adrenergic–Induced Cardiomyopathy
Authors: Gaussin Vinciane , Tomlinson James E. , Depre Christophe , Engelhardt Stefan , Antos Christopher L. , Takagi Gen , Hein Lutz , Topper James N. , Liggett Stephen B. , Olson Eric N. , Lohse Martin J. , Vatner Stephen F. , Vatner Dorothy E.
Published: November 2003

Background—

Although β-adrenergic receptor (AR) blockade therapy is beneficial in the treatment of heart failure, little is known regarding the transcriptional mechanisms underlying this salutary action.

Methods and Results—

In the present study, we screened mice overexpressing Gsα, β
1
AR, β
2
AR, or protein kinase A to test if a common genomic pathway exists in different models with enhanced β-adrenergic signaling. In mice overexpressing Gsα, differentially expressed genes were identified by mRNA profiling. In addition to well-known markers of cardiac hypertrophy (atrial natriuretic factor, CARP, and β-myosin heavy chain), uncoupling protein 2 (UCP2), a protein involved in the control of mitochondrial membrane potential, and four-and-a-half LIM domain protein-1 (FHL1), a member of the LIM protein family, were predicted to be upregulated. Upregulation of these genes was confirmed by quantitative reverse transcriptase–polymerase chain reaction at all time points tested during the development of cardiomyopathy in mice overexpressing Gsα. In mice overexpressing β
1
AR, β
2
AR, or protein kinase A, increased UCP2 and FHL1 expression was also observed at the onset of cardiomyopathy. βAR blockade treatment reversed the cardiomyopathy and suppressed the increased expression of UCP2 and FHL1 in mice overexpressing Gsα.

Conclusions—

UCP2 and FHL1 are important candidate genes that correlate with the development of βAR-induced cardiomyopathy in different mouse models with enhanced βAR signaling. In addition to preserving cardiac function, βAR blockade treatment also prevents the genomic regulation that correlates with the onset of heart failure.