bluuebunny/crossref_metadata_2025 huggingface dataset:
Recruitment of Neutrophils across the Blood–Brain Barrier: The Role of E- and P-selectins
Authors: Bernardes-Silva Martine , Anthony Daniel C. , Issekutz Andrew C. , Perry V. Hugh
Published: November 2003

The adult central nervous system parenchyma is resistant to inflammation, but in juvenile rats the injection of inflammatory mediators, interleukin-1β for example, gives rise to extensive neutrophil recruitment and neutrophil-dependent blood–brain barrier breakdown. The factors that confer this resistant phenotype are unknown. In this study, the authors demonstrate that E- and P-selectin expression is increased to a similar extent in adult and juvenile brain after the intracerebral injection of IL-1β. Thus, the refractory nature of the brain parenchyma cannot be attributed to an absence of selectin expression. However, in injuries where the resistant characteristic of the brain parenchyma is compromised, and neutrophil recruitment occurs, selectin blockade may be an advantage. The authors investigated the contribution that selectins make to neutrophil recruitment during acute inflammation in the brain. The authors examined neutrophil recruitment by immunohistochemistry on brain sections of juvenile rats killed four hours after the intracerebral injection of IL-1β and the intravenous injection of neutralizing anti-selectin monoclonal antibodies (mAb). The administration of the P-selectin blocking mAb inhibited neutrophil recruitment by 85% compared with controls. Surprisingly, E-selectin blockade had no effect on neutrophil recruitment to the brain parenchyma. Thus, P-selectin appears to play a pivotal role in mediating neutrophil recruitment to the brain parenchyma during acute inflammation.
Neuroprotective Effects of the CRF1 Antagonist R121920 after Permanent Focal Ischemia in the Rat
Authors: Mackay Kenneth B. , Bozigian Haig , Grigoriadis Dimitri E. , Loddick Sarah A. , Verge Gail , Foster Alan C.
Published: November 2003

The neuroprotective effects of a systemically active, highly selective, corticotropin-releasing factor-1 (CRF1) receptor antagonist, R121920 ((7-(dipropylamino)-2,5-dimethyl-3- [2-(dimethylamino)-5-pyridyl] pyrazolo [1,5-a] pyrimidine), was assessed in two rat models of permanent focal cerebral ischemia, where the middle cerebral artery (MCA) was occluded either through the subtemporal approach or using the intraluminal suture technique. R121920 rapidly crossed the blood–brain barrier after intravenous (IV) bolus administration (10 mg/kg), with peak brain concentrations at 5 minutes (2.26 ± 0.40 μg/mL), which were approximately 2-fold greater than those in plasma (0.98 ± 0.24 μg/mL). Treatment with R121920 (10 mg/kg IV followed by 5 mg/kg subcutaneously at hourly intervals for 4 hours) significantly ( P < 0.001) reduced total (by 40%) and cortical (by 37%) infarct volume at 24 hours after subtemporal MCA occlusion (MCAO). In the intraluminal suture MCAO model, IV administration of R121920 (10 mg/kg) at the time of ischemia onset (and at multiple times thereafter) reduced both hemispheric infarct volume (by 34%, P < 0.001) and brain swelling (by 50%, P < 0.001) when assessed at 24 hours. In this model of focal ischemia, significant reduction ( P < 0.05) in both outcome measures was obtained when R121920 administration was delayed up to 1 hour after MCAO. These results further define the antiischemic properties of selective CRF1 antagonists in two experimental models of permanent focal cerebral ischemia.
Inhibition of Cyclin-Dependent Kinases Improves CA1 Neuronal Survival and Behavioral Performance after Global Ischemia in the Rat
Authors: Wang Fuhu , Corbett Dale , Osuga Hitoshi , Osuga Sachiko , Ikeda Joh-E , Slack Ruth S. , Hogan Matthew J. , Hakim Antoine M. , Park David S.
Published: November 2003

Increasing evidence suggests that cyclin-dependent kinases participate in neuronal death induced by multiple stresses in vitro. However, their role in cell death paradigms in vivo is not well characterized. Accordingly, the authors examined whether cyclin-dependent kinase inhibition resulted in functionally relevant and sustained neuroprotection in a model of global ischemia. Intracerebroventricular administration of the cyclin-dependent kinase inhibitor flavopiridol, immediately or at 4 hours postreperfusion after a global insult, reduced injury in the CA1 of the hippocampus when examined 7 days after reperfusion. No significant protection was observed when flavopiridol was administered 8 hours after reperfusion. The tumor-suppressor retinoblastoma protein, a substrate of cyclin-dependent kinase, was phosphorylated on a cyclin-dependent kinase consensus site after the global insult; this phosphorylation was inhibited by flavopiridol administration. Importantly, flavopiridol had no effect on core body temperature, suggesting that the mechanism of neuroprotection was through cyclin-dependent kinase inhibition but not through hypothermia. Furthermore, inhibition of cyclin-dependent kinases improved spatial learning behavior as assessed by the Morris water maze 7 to 9 days after reperfusion. However, the histologic protection observed at day 7 was absent 28 days after reperfusion. These results indicate that cyclin-dependent kinase inhibition provides an extended period of morphologic and functional neuroprotection that may allow time for other neuroprotective modalities to be introduced.
Glycoprotein IIb/IIIa Antagonist, Murine 7E3 F(ab′)2, and Tissue Plasminogen Activator in Focal Ischemia: Evaluation of Efficacy and Risk of Hemorrhage with Combination Therapy
Authors: Shuaib Ashfaq , Yang Yi , Nakada Marian T. , Li Qiu , Yang Tao
Published: November 2003

Tissue hypoperfusion during cerebral ischemia results from occlusion of large and small vessels. Combination treatment strategies using fibrinolytics to thrombolyse an embolic clot and antiplatelet agents to prevent reocclusion and the formation of new platelet thrombi in the microcirculation may offer advantages over single-agent therapy. The authors report on the effects of tissue plasminogen activator (rt-PA), a glycoprotein (GP) IIb/IIIa receptor antagonist, 7E3 F(ab′)2, or a combination of the two agents in a focal embolic model of cerebral ischemia in Wistar rats. Focal ischemia was produced by introducing an autologous thrombus into the right side middle cerebral artery. Forty-six male Wistar rats were randomly divided into 6 groups: control (n = 8), 7E3 F(ab′)2 (n = 9, 6 mg/kg), rt-PA (n = 9, 10 mg/kg), rt-PA (n = 6, 20 mg/kg), and 7E3 F(ab′)2 with either 10 mg/kg (n = 10) (low-dose combination) or 20 mg/kg (n = 6) (high-dose combination) rt-PA. Evaluation of neurobehavioral scores, cerebral angiography, bleeding time, and measurement of brain infarction volume were used to determine efficacy. All actively treated groups showed a significant reduction in the infarct volume. Animals treated with 7E3 F(ab′)2 showed reduced infarction volumes (24.0 ± 5.1%) compared with controls (42.43 ± 5.6%, P < 0.02). Treatment with rt-PA significantly reduced infarction volume (20.7 ± 3.3, = 0.01) at 10 mg/kg and at 20 mg/kg (19.5 ± 8.2%, P < 0.05). Compared with vehicle-treated animals, the low-dose combination (16.4 ± 5.5, P < 0.003) and high-dose combination (23.7 ± 6.2%, P < 0.05) showed significant reduction in infarction volume. Cerebral angiography revealed significantly better recanalization in the combination group (5/6 animals in the high dose and 4/6 in low dose) compared with animals treated with 7E3 F(ab′)2 (3/10) or rt-PA alone (2/6). Bleeding time significantly increased from 11.25 ± 1.9 minutes in the control group to 17 ± 3.1 minutes in the rt-PA group, 24.5 ± 2.6 minutes in the 7E3 F(ab′)2 group, 25.7 ± 3.1 minutes in the low-dose combination group, and 32.5 ± 4.7 minutes in the high-dose combination group. The incidence of intercerebral hemorrhage was highest in the high-dose combination group (6 of 6 animals) and lowest in the single treatment with 7E3 F(ab′)2 alone (1 of 10 animals) ( P < 0.05). Our data show that murine 7E3 F(ab′)2 alone has therapeutic effects when used after cerebral ischemia. Although this study suggests that higher doses of thrombolytic combined with anti-GPIIb/IIIa therapy may increases the risk of intracranial hemorrhage, the data also support the notion that anti-GPIIb/IIIa agents can safely be combined with low doses of thrombolytic agent to produce significant attenuation of neuronal damage with no increase in the incidence of cerebral hemorrhage.
Increase in Dopamine Turnover Occurs Early in Parkinson's Disease: Evidence from a New Modeling Approach to PET 18F-Fluorodopa Data
Authors: Sossi Vesna , de la Fuente-Fernández Raúl , Holden James E. , Doudet Doris J. , McKenzie Jess , Stoessl A. J. , Ruth T. J.
Published: November 2003

An increase in dopamine turnover has been hypothesized to occur early in Parkinson's disease (PD) as a compensatory mechanism for dopaminergic neuronal loss. A new approach to the determination of dopamine turnover was developed using 4-hour-long 18F-fluorodopa (FD) positron emission tomography (PET) data. An effective dopamine turnover, an estimate of dopamine turnover, has been measured using its inverse, the effective dopamine distribution volume (EDV). This new method is based on a reversible tracer approach and determines the EDV using a graphical method. Six healthy subjects and 10 subjects with very early PD underwent a 4-hour-long FD scan. The EDV and the plasma uptake rate constant Ki, a marker of dopamine synthesis and storage, were compared according to their ability to separate the PD group from the healthy group. The EDV was the better discriminator (93.8% correct classification versus 81.3% for Ki). Effective dopamine distribution volume decreased by 65% in the PD group relative to the healthy group, whereas the decrease in Ki was 39%. These results show that changes in EDV are measurable with PET earlier than changes in the dopamine synthesis and storage rate, indicating that EDV is a sensitive marker for early PD and that a dopamine turnover increase likely serves as an early compensatory mechanism.
Increased Proliferation of Neural Progenitor Cells but Reduced Survival of Newborn Cells in the Contralateral Hippocampus after Focal Cerebral Ischemia in Rats
Authors: Takasawa Ken-ichiro , Kitagawa Kazuo , Yagita Yoshiki , Sasaki Tsutomu , Tanaka Shigeru , Matsushita Kohji , Ohstuki Toshiho , Miyata Takaki , Okano Hideyuki , Hori Masatsugu , Matsumoto Masayasu
Published: November 2003

Recent studies demonstrated that neurogenesis in the adult hippocampus increased after transient global ischemia; however, the molecular mechanism underlying increased neurogenesis after ischemia remains unclear. The finding that proliferation of progenitor cells occurred at least a week after ischemic insult suggests that the stimulus was not an ischemic insult to progenitor cells. To clarify whether focal ischemia increases the rate of neurogenesis in the remote area, the authors examined the contralateral hemisphere in rats subjected to permanent occlusion of the middle cerebral artery. In the subgranular zone of the hippocampal dentate gyrus, the numbers of bromodeoxyuridine (BrdU)-positive cells increased approximately sixfold 7 days after ischemia. In double immunofluorescence staining, more than 80% of newborn cells expressed Musashi1, a marker of neural stem/progenitor cells, but only approximately 10% of BrdU-positive cells expressed glial fibrillary acidic protein (GFAP), a marker of astrocytes. The number of BrdU-positive cells markedly decreased 28 days after BrdU administration after ischemia, but it was still elevated compared with that of sham-operated rats. In double immunofluorescence staining, 80% of newborn cells expressed NeuN, a marker of differentiated neurons, and 10% of BrdU-positive cells expressed GFAP. However, in the other areas of the contralateral hemisphere including the rostral subventricular zone, the number of BrdU-positive cells remained unchanged. These results showed that focal ischemia stimulated the proliferation of neuronal progenitor cells, but did not support survival of newborn cells in the contralateral hippocampus.
The Systemic and Local Acute Phase Response following Acute Brain Injury
Authors: Wilcockson David C. , Campbell Sandra J. , Anthony Daniel C. , Perry V. Hugh
Published: November 2003

It is not known whether acute brain injury results in a systemic acute phase response (APR) or whether an APR influences outcome after an insult to the CNS. The present study sought to establish whether brain injury elicits a systemic or local APR. The expression of acute phase protein (APP) mRNA in liver and brain tissues was measured by Taqman reverse transcriptase-polymerase chain reaction after an excitotoxic lesion in the striatum or challenge with a proinflammatory cytokine. N-methyl-D-aspartate (NMDA)–induced brain lesion did not elicit a systemic APR. In contrast, proinflammatory challenge with mouse recombinant interleukin-1β (mrIL-1β) resulted in a significant hepatic APP mRNA expression within 6 hours. Thus, an inflammatory challenge that results in a meningitis leads to a hepatic APR, whereas acute brain injury alone, with no evidence of a meningitis, does not produce an APR. This is surprising because NMDA leads to an increase in endogenous IL-1β synthesis. This suggests that the brain has an endogenous antiinflammatory mechanism, which protects against the spread of inflammation after an acute injury. In the brain, both excitotoxic lesions and proinflammatory challenge resulted in a profound parenchymal upregulation of APP mRNA after 6 and 12 hours in the injected hemisphere. These results suggest that the local APR may play a role as an antiinflammatory mechanism. These findings indicate a potentially pivotal role for peripheral and local APP production on outcome after brain injury.
Near-Infrared Spectroscopy Cerebral Oxygen Saturation Thresholds for Hypoxia–Ischemia in Piglets
Authors: Kurth C. Dean , Levy Warren J. , McCann John
Published: November 2003

Detection of cerebral hypoxia–ischemia remains problematic in neonates. Near-infrared spectroscopy, a noninvasive bedside technology has potential, although thresholds for cerebral hypoxia–ischemia have not been defined. This study determined hypoxic–ischemic thresholds for cerebral oxygen saturation (Sco2) in terms of EEG, brain ATP, and lactate concentrations, and compared these values with CBF and sagittal sinus oxygen saturation (Svo2). Sixty anesthetized piglets were equipped with near-infrared spectroscopy, EEG, laser-Doppler flowmetry, and a sagittal sinus catheter. After baseline, Sco2 levels of less than 20%, 20% to 29%, 30% to 39%, 40% to 49%, 50% to 59%, 60% to 79%, or 80% or greater were recorded for 30 minutes of normoxic normocapnia, hypercapnic hyperoxia, or bilateral carotid occlusion with or without arterial hypoxia. Brain ATP and lactate concentrations were measured biochemically. Logistic and linear regression determined the Sco2, CBF, and Svo2 thresholds for abnormal EEG, ATP, and lactate findings. Baseline Sco2 was 68 + 5%. The Sco2 thresholds for increased lactate, minor and major EEG change, and decreased ATP were 44 ± 1%, 42 ± 5%, 37 ± 1%, and 33 ± 1%. The Sco2 correlated linearly with Svo2 (r = 0.98) and CBF (r = 0.89), with corresponding Svo2 thresholds of 23%, 20%, 13%, and 8%, and CBF thresholds (% baseline) of 56%, 52%, 42%, and 36%. Thus, cerebral hypoxia-ischemia near-infrared spectroscopy thresholds for functional impairment are Sco2 33% to 44%, a range that is well below baseline Sco2 of 68%, suggesting a buffer between normal and dysfunction that also exists for CBF and Svo2.
Magnetic Resonance Angiography of Thromboembolic Stroke in Rats: Indicator of Recanalization Probability and Tissue Survival after Recombinant Tissue Plasminogen Activator Treatment
Authors: Hilger Thomas , Niessen Frank , Diedenhofen Michael , Hossmann Konstantin-Alexander , Hoehn Mathias
Published: November 2003

Magnetic resonance angiography (MRA) was performed in a thromboembolic stroke model of the rat to characterize intracranial vessel occlusion patterns and to test its predictive power for tissue recovery after recombinant tissue plasminogen activator (rt-PA) treatment. After rt-PA-treated selective middle cerebral artery (MCA) occlusion, full recanalization was observed in two of three animals, whereas additional occlusion of the circle of Willis (CW) resulted in full vascular flow restitution in only one of six rats. Tissue reperfusion markedly lagged the onset of treatment, and the delay correlated with the pattern of vessel occlusion (20 to 23 minutes for selective MCA occlusion vs. 71 to 79 minutes for combined MCA/CW occlusion). In lateral cortex and striatum the apparent diffusion coefficient decreased to 78 ± 15% of control after embolization, recovered to 80% to 85% after rt-PA treatment of selective MCA occlusion, but further declined to 66% to 69% after combined MCA/CW occlusion. Correspondingly, T2 relaxation time increased to 107% to 118% of control after selective MCA occlusion and to 112% to 124% after combined MCA/CW occlusion in these regions. The present investigation shows that MRA provides valuable information on the severity of thromboembolic stroke and has the power to predict, before the initiation of treatment, the functional tissue outcome after rt-PA-induced thrombolysis.
Hypoxia-Inducible Factor-1α Accumulation in the Brain after Experimental Intracerebral Hemorrhage
Authors: Jiang Yajun , Wu Jimin , Keep Richard F. , Hua Ya , Hoff Julian T. , Xi Guohua
Published: November 2003

Hypoxia-inducible factor-1 (HIF-1), a transcription factor composed of HIF-1α and HIF-1β protein subunits, has been implicated in cellular protection and cell death in cerebral ischemia. The extent to which HIF-1 plays a role in brain pathology during intracerebral hemorrhage (ICH) is unknown. This study determined whether HIF-1α is upregulated at different time points in a rat model of ICH and the role of thrombin and red blood cell lysis in upregulation. Recently, thrombin has been implicated as a nonhypoxic regulator of HIF-1α in cultured smooth-muscle cells. Male Sprague-Dawley rats received intracerebral infusions of saline, autologous whole blood, blood plus hirudin, thrombin, thrombin plus hirudin, or lysed erythrocytes. Rats were killed at different time points for Western blot analysis, immunohistochemistry, immunofluorescent double staining, and reverse transcription polymerase chain reaction measurements of HIF-1α. HIF-1α protein levels increased without changing HIF-1α messenger RNA levels after intracerebral infusions of blood, thrombin, and lysed erythrocytes. HIF-1α positive cells, which proved to be neurons, were found in the brain after ICH. Hirudin, a specific thrombin inhibitor, reduced HIF-1α upregulation in response to both thrombin and blood. This study demonstrates that perihematomal HIF-1α protein is upregulated after ICH. This phenomenon is an early response of brain parenchyma to the clot. Thrombin and erythrocyte lysate are involved in HIF-1α upregulation through reducing HIF-1α degradation.
Comet Assay as a Novel Approach for Studying DNA Damage in Focal Cerebral Ischemia: Differential Effects of NMDA Receptor Antagonists and Poly(ADP-Ribose) Polymerase Inhibitors
Authors: Giovannelli Lisa , Cozzi Andrea , Guarnieri Ilaria , Dolara Piero , Moroni Flavio
Published: November 2003

The single-cell gel electrophoresis (comet assay) was used to evaluate the possibility of detecting single-strand breaks of brain DNA in the early phase of ischemia. Four hours after occlusion of the middle cerebral artery (MCAO) in rats, the percentage of DNA migrating into the comet tail (indicating the presence of breaks) increased from 11.4 ± 4.70 to 34.7 ± 9.2 (means ± SD) in the caudate and from 9.9 ± 4.3 to 42.8 ± 14.1 in the cortex. Interestingly, a subpopulation of cells exhibiting higher resistance to the ischemic insult was present in the caudate putamen, but not in the cortex. Administration of MK801, an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist, (1 mg/kg subcutaneously, 10 minutes before MCAO), reduced the ischemia-induced DNA breaks and the infarct volume, suggesting that excessive stimulation of NMDA receptors contributes to the formation of both DNA damage and infarct volume. In contrast, DPQ, an inhibitor of poly(ADP-ribose) polymerase (PARP) (10 mg/kg intraperitoneally, 2 hours before and 1 hour after MCAO), reduced the infarct volume but not DNA damage, suggesting that the neuroprotective actions of PARP inhibitors occur at a later step of the processes leading to postischemic neuronal death.
Burn Center Management of Necrotizing Fasciitis
Authors: Barillo David J. , McManus Albert T. , Cancio Leopoldo C. , Sofer Alfred , Goodwin Cleon W.
Published: November 2003

Necrotizing fasciitis is a rapidly progressive soft-tissue infection associated with significant morbidity and mortality. Necrotizing fasciitis is similar to invasive burn wound infection in that diagnosis requires histologic examination of affected tissue and treatment requires aggressive surgical debridement followed by skin autograft. Transfer to a burn center facilitates the management of necrotizing fasciitis, where requisite surgical and nursing expertise is available. We reviewed the experience of one burn center in the management of necrotizing fasciitis over a 5-year period. Ten patients were transferred to the burn center from other medical facilities for care, arriving a mean of 8.9 days after initial hospital admission. The diagnosis was made by a surgical service or consultation before transfer in all cases; initial admission to a medical rather than a surgical service delayed surgery in five cases. All patients had surgical debridement before transfer but required a mean of 5.1 additional operations at the burn center. Although the mean extent of involvement was 14.8% body surface area, the mean length of burn center stay was 34.9 days. Complications were frequent, including pulmonary failure requiring mechanical ventilation (n = 6), renal insufficiency or failure (n = 5), hypotension requiring pressers (n = 4), deep venous thrombosis (n = 3), and pulmonary emboli (n = 1). Overall mortality was 2 of 10 patients (20%). Both fatalities were associated with delay in initial surgical procedure and in transfer to the burn center. The similarity of necrotizing fasciitis and invasive burn wound infection makes the burn center the ideal setting for the treatment of this disease. We advocate the addition of necrotizing fasciitis to the list of conditions currently recognized by the American Burn Association as appropriate for burn center transfer and care.
Fusarium Infections in Burn Patients: A Case Report and Review of the Literature
Authors: Latenser Barbara A.
Published: November 2003

Fusarium species, or saprophytic molds, are important plant pathogens and recognized as agents of human mycotic infections. Frequently superficial, deep-tissue involvement, and dissemination occurs in immunocompromised hosts with hematologic malignancies, aplastic anemia, and chemotherapy treatment. Presented in this work is a burn patient with a fatal disseminated infection in addition to a review of the literature. A 40-year-old white male acquired a 73% grease scald injury at work. His hospital course was interspersed with multiple episodes of Flavobacterium, Fusarium, Candida, Proteus, Enterococcus, coagulase-negative Staphylococcus, and Serratia infections. He underwent nine operative procedures for debridement, excision, and skin grafting. The last operative procedure included bilateral below knee amputations to halt an invasive Fusarium infection that was invading normal unburned skin. The patient died 55 days after injury. Fusarium and Aspergillus infections are frequently confused and do not have characteristic clinical features. With the prolonged survival of severely burned patients, better fungal diagnostic and treatment modalities are needed to improve outcome.
Relation between Cerebral Blood Flow and Metabolism Explained by a Model of Oxygen Exchange
Authors: Valabrègue Romain , Aubert Agnès , Burger Jacques , Bittoun Jacques , Costalat Robert
Published: November 2003

The cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) are major determinants of the contrast in functional magnetic resonance imaging and optical imaging. However, the coupling between CBF and CMRO2 during cerebral activation remains controversial. Whereas most of the previous models tend to show a nonlinear coupling, experimental studies have led to conflicting conclusions. A physiologic model was developed of oxygen transport through the blood–brain barrier (BBB) for dynamic and stationary states. Common model simplifications are proposed and their implications for the CBF/CMRO2 relation are studied. The tissue oxygen pool, the BBB permeability, and the hemoglobin dissociation curve are physiologic parameters directly involved in the CBF/CMRO2 relation. We have been shown that the hypothesis of a negligible tissue oxygen pool, which was admitted by most of the previous models, implies a tight coupling between CBF and CMRO2. By relaxing this hypothesis, a real uncoupling was allowed that gives a more coherent view of the CBF/CMRO2 relation, in better agreement with the hypercapnia data and with the variability reported in experimental works for the relative changes of those two variables. This also allows a temporal mismatch between CBF and CMRO2, which influences the temporal shape of oxygenation at the capillary end.
Effects of 2-Deoxy-D-Glucose on Focal Cerebral Ischemia in Hyperglycemic Rats
Authors: Wei Jingna , Cohen David M. , Quast Michael J.
Published: November 2003

The authors examined the effects of pretreatment with 2-deoxy-D-glucose (2DG) on the middle cerebral artery occlusion–reperfusion (MCAO/R) model in hyperglycemic rats. Proton magnetic resonance imaging and spectroscopy were used to measure the lesion size, the level of cerebral perfusion deficit, and ratio of lactate to N-acetyl aspartate (NAA) in brain regions. By performing sequential diffusion weighted imaging, gradient echo bolus tracking, steady-state spin echo imaging, and water-suppressed proton magnetic resonance spectroscopy techniques, the time course of the early changes of the lactate/NAA peak ratio and perfusion deficit was examined in hyperglycemic rats undergoing 90-minute MCAO followed by 24-h reperfusion. Compared with the saline-treated hyperglycemic rats, 2DG treatment at 10 minutes before MCAO significantly reduced diffusion weighted imaging hyperintensity by ∼60% and the lactate/NAA peak ratio by ∼70% at 4 h after MCAO/R. Both spin echo–measured cerebral blood volume and dynamic gradient echo–relative cerebral blood flow showed that the restoration of blood supply recovered and remained at ∼80% of baseline during reperfusion in 2DG-treated hyperglycemic rats. These data suggest that inhibition of glucose metabolism by 2DG has a beneficial effect in reducing brain injury and minimizing the production of brain lactate during MCAO/R in hyperglycemic rats.
Arteriogenesis in Hypoperfused Rat Brain
Authors: Busch Hans-Jörg , Buschmann Ivo R. , Mies Günter , Bode Christoph , Hossmann Konstantin-Alexander
Published: November 2003

Experimental and clinical studies have provided evidence for spontaneous and therapeutically induced arteriogenesis after occlusion of major peripheral or cardiac vessels. Such evidence is lacking for the cerebrovascular system. In halothane-anesthetized rats, different degrees of brain hypoperfusion were induced by one- to four-vessel occlusion, that is, one or both common carotid arteries in combination with or without bilateral vertebral artery occlusion. The flow decline was monitored by laser Doppler flowmetry, the residual hemodynamic reserve by testing flow reactivity to ventilation with 6% CO2 and arteriogenesis by intravascular latex infusion and immunohistochemistry of vascular proliferation and monocyte adhesion. The optimum condition for induction of arteriogenesis was three-vessel (one carotid plus both vertebral arteries) occlusion, which led to reduction of blood flow to about 50% and complete suppression of CO2 reactivity, but no histologic injury. One week after three-vessel occlusion, the ipsilateral posterior cerebral artery significantly enlarged by 39%, and after 3 weeks by 72%, paralleled by the partial return of CO2 reactivity and the appearance of immunohistochemical markers of arteriogenesis. Three-vessel occlusion is a reliable model for the induction of arteriogenesis in the adult brain and is a new approach for exploring the potentials of arteriogenesis for the prevention of progressing brain ischemia.
Role of Nitric Oxide in Cerebral Blood Flow Abnormalities after Traumatic Brain Injury
Authors: Hlatky Roman , Goodman J. Clay , Valadka Alex B. , Robertson Claudia S.
Published: November 2003

Nitric oxide (NO) has important regulatory functions within the central nervous system. NO is oxidized in vivo to nitrate and nitrite (NOx). Measurement of these products gives an index of NO production. The purpose of this study was to examine the relation between the brain extracellular concentration of NO metabolites and cerebral blood flow (CBF) after severe traumatic brain injury. Using a chemiluminescence method, NOx concentrations were measured in 6,701 microdialysate samples obtained from 60 patients during the first 5 d after severe head injury. Regional and global values of CBF obtained by xenon-enhanced computed tomography were used for analyses. Dialysate NOx values were the highest within the first 24 h after brain trauma and gradually decreased over the 5 postinjury d (time effect, P < 0.001). Mean dialysate concentration of NOx was 15.5 ± 17.6 μmol/L (minimum 0.3, maximum 461 μmol/L) and 65% of samples were between 5 and 20 μmol/L. There was a significant relation between regional CBF and dialysate NOx levels (r2 = 0.316, P < 0.001). Dialysate NOx levels (9.5 ± 2.2 μmol/L) in patients with critical reduction of regional CBF (<18 mL · 100 g−1 · min−1) were significantly lower than in patients with normal CBF (18.6 ± 8.1 μmol/L; P < 0.001). This relation between the dialysate concentration of NOx and regional CBF suggests some role for NO in the abnormalities of CBF that occur after traumatic brain injury.
Improved Statistical Power of the Multilinear Reference Tissue Approach to the Quantification of Neuroreceptor Ligand Binding by Regularization*
Authors: Buchert Ralph , Wilke Florian , van den Hoff Jörg , Mester Janos
Published: November 2003

A multilinear reference tissue approach has been widely used recently for the assessment of neuroreceptor–ligand interactions with positron emission tomography. The authors analyzed this “multilinear method” with respect to its sensitivity to statistical noise, and propose regularization procedures that reduce the effects of statistical noise. Computer simulations and singular value decomposition of its operational equation were used to investigate the sensitivity of the multilinear method to statistical noise. Regularization was performed by truncated singular value decomposition, Tikhonov-Phillips regularization, and by imposing boundary constraints on the rate constants. There was a significant underestimation of distribution volume ratios. Singular value decomposition showed that the bias was caused by statistical noise. The regularization procedures significantly increased the test–retest stability. The bias could be reduced by applying linear constraints on the rate constants based on their normal range. Underestimation of distribution volume ratios by the multilinear method is caused by its sensitivity to statistical noise. Statistical power in the discrimination of different groups of subjects can be significantly improved by regularization procedures without introducing additional bias. Correct distribution volume ratios can be obtained by imposing physiologic constraints on the rate constants.
Inhibition of Apoptosis by Hyperbaric Oxygen in a Rat Focal Cerebral Ischemic Model
Authors: Yin Dali , Zhou Changman , Kusaka Ikuyo , Calvert John W. , Parent Andrew D. , Nanda Anil , Zhang John H.
Published: November 2003

The hypothesis was tested that hyperbaric oxygen therapy (HBO) reduced brain infarction by preventing apoptotic death in ischemic cortex in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and subsequently were exposed to HBO (2.5 atmospheres absolute) for 2 h, at 6 h after reperfusion. Rats were killed and brain samples were collected at 24, 48, 72 h, and 7 days after reperfusion. Neurologic deficits, infarction area, and apoptotic changes were evaluated by clinical scores, 2,3,7-triphenyltetrazolium chloride staining, caspase-3 expression, DNA fragmentation assay, and terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL)-hematoxylin and eosin (H&E) costaining. In MCAO/R without HBO treatment animals, DNA fragmentation was observed in injured cortex at 24, 48, and 72 h but not in samples at 7 days after reperfusion. Double labeling of brain slides with NeuN and caspase-3 demonstrated neurons in the injured cortex labeled with caspase-3. TUNEL+H&E costaining revealed morphologic apoptotic changes at 24, 48, and 72 h after reperfusion. Hyperbaric oxygen therapy abolished DNA fragmentation and reduced the number of TUNEL-positive cells. Hyperbaric oxygen therapy reduced infarct area and improved neurologic scores at 7 days after reperfusion. One of the molecular mechanisms of HBO-induced brain protection is to prevent apoptosis, and this effect of HBO might preserve more brain tissues and promote neurologic functional recovery.
Democracy and information: transmitters and receivers
Authors: Line Maurice B.
Published: November 2003

Democracy, recognised as a flawed but desirable system of government, relies ultimately on trusting the people, whose views are therefore of prime importance. Their views therefore need to be well informed if democracy is to work successfully. The main formers of opinion, television and the press, commonly distort or over‐simplify issues such as crime and asylum. There is plenty of reliable information available; the problem is that most people are not equipped intellectually or psychologically to desire information, to access it, to challenge it and to discriminate between good and bad. Development of such characteristics is a task for the education system; narrow “information literacy” programmes are not enough. Libraries, as resources and channels of information, are essential elements in the provision of a wide range of knowledge and opinion.
Freedom of access to information and freedom of expression: the Internet as a tool for global social inclusion
Authors: Hamilton Stuart , Ole Pors Niels
Published: November 2003

This paper explores how the relationship between freedom of access to information and freedom of expression is expressed across the international library community. Specifically, it analyses this relationship in the setting of Internet access in libraries where the Internet has been seen as a tool for fostering democracy and furthering social inclusion. Using preliminary analysis of data collected from a global survey of Internet access issues within the International Federation of Library Associations and Institutions (IFLA) member countries (2003), and by comparing this data with a survey of European library institutions carried out in 2002, the paper shows the extent to which libraries – from the point of view of national associations and national libraries – are able to use the Internet to promote freedom of access to information and freedom of expression despite the existence of barriers to this task.
Continuing professional development and workplace learning 5: human resource development – a strategic imperative
Authors: Smith Ian
Published: November 2003

Discusses the importance of a strategic approach to human resource development (HRD) in an environment of rapid change. HRD is defined and the characteristics of strategic HRD are identified. Puts the view that HRD is a strategic imperative – nationally, organisationally and individually. Outlines themes that are to be developed in a series of brief articles in coming issues of Library Management.
Success factors in e‐channels: the Malaysian banking scenario
Authors: Hway‐Boon Ong , Ming Yu Cheng
Published: November 2003

One of the most significant implications of technological advances in the banking sector is the possibility of delivering banking services through electronic channels (e‐channels). E‐channels provide alternatives for faster delivery of banking services to a wider scope of customers. Nowadays, e‐channels have gained increasing popularity in delivering banking services. However, prior to the implementation of e‐channels, several factors and investment costs must be identified to ensure a more cost effective and efficient execution of e‐channel services. A survey is thus conducted to determine factors that are essential for the successful implementation of e‐channels by domestic commercial banks in Malaysia. Data were collected from primary sources and were analysed via frequency analysis and factor analysis. The results of the survey suggested that banks’ operation management is the main factor affecting the success of ATMs, PC and branch banking, while product innovation and knowledge development factors are found to have the most significant effect on the success of banking kiosks and phone banking respectively.
Operations strategy formation – a continuous process
Authors: Nielsen‐Englyst Linda
Published: November 2003

This article describes and analyses observations from a longitudinal case study to advance an understanding of operations strategy formation as a continuous process. The managerial practices of the case company are analysed in relation to four general desired outcomes of a strategy process, and a process design is constructed as an example of good practice. Regarding strategy formation as a continuous part of the normal management process, the process design is proposed as a relevant alternative to the traditional discontinuous practice of strategy formation. The interplay between modes of strategy formation in different phases of the process is discussed, indicating the varying roles of managers.
Exploring the contours of supply chain management
Authors: Mouritsen Jan , Skjøtt‐Larsen Tage , Kotzab Herbert
Published: November 2003

Supply chain management (SCM) is becoming a popular concept both in research and in practice. At the EurOMA Conference in Copenhagen in 2002 many papers focused on SCM as a research topic. Similarly, an increasing number of companies are establishing positions as supply chain managers. SCM is also a popular theme for trade journals and management conferences. The quest for integration is an explicit or implicit assumption in most literature within SCM. The basic hypothesis is “the more integration – the better the management of the chain”. This article discusses what the term “management” in the concept of SCM stands for. The integration assumption as a “cure all” prescription for SCM is challenged, and questions raised as to when it is possible and desirable to exercise management in supply chains. The main thesis is that it depends very much on the “environment” of the supply chain and the power relations between the participants in the supply chain.
Benefits of involving users in service innovation
Authors: Magnusson Peter R.
Published: November 2003

Past research has demonstrated that industrial customers can, in effect, bring about product innovation among their suppliers. However, little seems to be known as to whether consumers are also potential inventors of new services. Presents results from an empirical study with the objective of exploring whether ordinary users can contribute novel service ideas regarding mobile telephony. An experimental approach was used to compare the characteristics of new services suggested by ordinary users with services suggested by professional developers. It was found that the service innovations suggested by the users were more creative and useful than those suggested by the professionals. On the other hand, the suggestions of the professionals were deemed easier to produce. Concludes with a discussion on the contributions and limitations of user involvement, wherein the organisational role of the users involved is discussed. Also makes a proposal regarding how to further investigate the potential of the user as a co‐worker in the innovation process.
Regulation of L‐type calcium current by intracellular magnesium in rat cardiac myocytes
Authors: Wang Min , Tashiro Michiko , Berlin Joshua R.
Published: November 2003

The effects of changing cytosolic [Mg2+] ([Mg2+]i) on l‐type Ca2+ currents were investigated in rat cardiac ventricular myocytes voltage‐clamped with patch pipettes containing salt solutions with defined [Mg2+] and [Ca2+]. To control [Mg2+]i and cytosolic [Ca2+] ([Ca2+]i), the pipette solution included 30 mm citrate and 10 mm ATP along with 5 mm EGTA (slow Ca2+ buffer) or 15 mm EGTA plus 5 mm BAPTA (fast Ca2+ buffer). With pipette [Ca2+] ([Ca2+]p) set at 100 nm using a slow Ca2+ buffer and pipette [Mg2+] ([Mg2+]p) set at 0.2 mm, peak l‐type Ca2+ current density (ICa) was 17.0 ± 2.2 pA pF−1. Under the same conditions, but with [Mg2+]p set to 1.8 mm, ICa was 5.6 ± 1.0 pA pF−1, a 64 ± 2.8% decrease in amplitude. This decrease in ICa was accompanied by an acceleration and a –8 mV shift in the voltage dependence of current inactivation. The [Mg2+]p‐dependent decrease in ICa was not significantly different when myocytes were preincubated with 10 μm forskolin and 300 μm 3‐isobutyl‐1‐methylxanthine and voltage‐clamped with pipettes containing 50 μm okadaic acid, to maximize Ca2+ channel phosphorylation. However, when myocytes were voltage‐clamped with pipettes containing protein phosphatase 2A, to promote channel dephosphorylation, ICa decreased only 25 ± 3.4% on changing [Mg2+]p from 0.2 to 1.8 mm. In the presence of 0.2 mm[Mg2+]p, changing channel phosphorylation conditions altered ICa over a 4‐fold range; however, with 1.8 mm[Mg2+]p, these same manoeuvres had a much smaller effect on ICa. These data suggest that [Mg2+]i can antagonize the effects of phosphorylation on channel gating kinetics. Setting [Ca2+]p to 1, 100 or 300 nm also showed that the [Mg2+]p‐induced reduction of ICa was smaller at the lowest [Ca2+]p, irrespective of channel phosphorylation conditions. This interaction between [Ca2+]i and [Mg2+]i to modulate ICa was not significantly affected by ryanodine, fast Ca2+ buffers or inhibitors of calmodulin, calmodulin‐dependent kinase and calcineurin. Thus, physiologically relevant [Mg2+]i modulates ICa by counteracting the effects of Ca2+ channel phosphorylation and by an unknown [Ca2+]i‐dependent mechanism. The magnitude of these effects suggests that changes in [Mg2+]i could be critical in regulating l‐type channel gating.
Synapses between parallel fibres and stellate cells express long‐term changes in synaptic efficacy in rat cerebellum
Authors: Rancillac Armelle , Crépel Francis
Published: November 2003

Various forms of synaptic plasticity underlying motor learning have already been well characterized at cerebellar parallel fibre (PF)–Purkinje cell (PC) synapses. Inhibitory interneurones play an important role in controlling the excitability and synchronization of PCs. We have therefore tested the possibility that excitatory synapses between PFs and stellate cells (SCs) are also able to exhibit long‐term changes in synaptic efficacy. In the present study, we show that long‐term potentiation (LTP) and long‐term depression (LTD) were induced at these synapses by a low frequency stimulation protocol (2 Hz for 60 s) and that pairing this low frequency stimulation protocol with postsynaptic depolarization induced a marked shift of synaptic plasticity in favour of LTP. This LTP was cAMP independent, but required nitric oxide (NO) production from pre‐ and/or postsynaptic elements, depending on the stimulation or pairing protocol used, respectively. In contrast, LTD was not dependent on NO production but it required activation of postsynaptic group II and possibly of group I metabotropic glutamate receptors. Finally, stimulation of PFs at 8 Hz for 15 s also induced LTP at PF–SC synapses. But in this case, LTP was cAMP dependent, as was also observed at PF–PC synapses for presynaptic LTP induced in the same conditions. Thus, long‐term changes in synaptic efficacy can be accomplished by PF–SCs synapses as well as by PF–PC synapses, suggesting that both types of plasticity might co‐operate during cerebellar motor learning.
An extension of Thomson’s theorem and its application for determining induced charge densities
Authors: Donolato C.
Published: November 2003

Thomson’s theorem of electrostatics states that the equilibrium distribution of charge on a system of conductors is that of minimum energy relative to other charge distributions with the same amount of charge on each conductor. By an appropriate modification of the energy functional, the theorem is extended to the case where the potential of some conductors, rather than their charge, is fixed. This extension is of interest in the analysis of electrostatic induction. The basic theorem and its extension are applied to a spherical conductor in the presence of a point charge or placed in a uniform external field. The known expressions for the induced surface charge density in different conditions are obtained from the direct minimization of the new functional on the basis of a simple argument.
Testing a Model for Sliding Motion on an Incline
Authors: Martin Brian E. , Connors Martin
Published: November 2003

Physics is all about making models of how the world works. Communicating this to students is an important part of what we do as physics educators. In this paper we describe a simple apparatus and experiment that can be used to investigate sliding motion on an incline. Such motion is realistic and tangible yet easily analyzed with modern equipment and techniques. Data obtained can be used to introduce students to the use of two-parameter fitting to test a simple physical model. It also provides an accurate experimental determination of the local acceleration of gravity and a coefficient of friction.
Adhesives for seed placement during artificial inoculation of Pinus banksiana seedlings with the dwarf mistletoe Arceuthobium americanum
Authors: Brandt J P , Hiratsuka Y , Pluth D J
Published: November 2003

Lodgepole pine dwarf mistletoe (Arceuthobium americanum Nutt. ex Engelm.) is a serious pest of jack pine (Pinus banksiana Lamb.). Research investigating factors such as host resistance, influence of host nutrition on infection rates, and effect of temperature and humidity on the life cycle of the pathogen is limited by our ability to consistently infect the host through artificial means. A greenhouse experiment utilizing a completely randomized design with four replicates was conducted to test the effectiveness of three chemical compounds and the natural viscin of the dwarf mistletoe seed to act as adhesives during artificial inoculation of jack pine seedlings. Synthetic adhesives used were anhydrous lanolin (LAN), hydroxypropylcellulose (HPC), and polyvinyl acetate (PVA). The percentage of infected seedlings was significantly higher with HPC compared with that of PVA, LAN, and the seed's viscin. HPC, as the superior adhesive, and the techniques described should allow consistent production of seedlings infected with dwarf mistletoe for research, regardless of the dwarf mistletoe species involved. Problems encountered during the testing of the adhesives are discussed in relation to the nature of the adhesives and their application.Key words: anhydrous lanolin, hydroxypropylcellulose, polyvinyl acetate, viscin.