bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Normobaric Hyperoxia in a Rat Model of Focal Cerebral Ischemia—Reperfusion
Authors: Singhal Aneesh B. , Wang Xiaoying , Sumii Toshihisa , Mori Tatsuro , Lo Eng H.
Published: November 2003

Recent studies suggest that normobaric hyperoxia can be beneficial, if administered during transient stroke. However, increased oxygenation theoretically may increase oxygen free-radical injury, particularly during reperfusion. In the present study, the authors assessed the benefit and risks of hyperoxia during focal cerebral ischemia and reperfusion. Rats were subjected to hyperoxia (Fio2 100%) or normoxia (Fio2 30%) during 2-hour filament occlusion and 1-hour reperfusion of the middle cerebral artery. At 24 hours, the hyperoxia group showed 70% (total) and 92% (cortical) reduction in infarct volumes as compared to the normoxia group. Levels of oxidative stress were evaluated using three indirect methods. First, since oxygen free radicals increase blood—brain barrier (BBB) damage, Evan's blue dye extravasation was quantified to assess BBB damage. Second, the expression of heme oxygenase-1 (HO-1), a heat shock protein inducible by oxidative stress, was assessed using Western blot techniques. Third, an immunoblot technique (“OxyBlot”) was used to assess levels of protein carbonyl formation as a marker of oxidative stress—induced protein denaturation. At 24 hours, Evan's blue dye extravasation per average lesion volume was similar between groups. There were no significant differences in HO-1 induction and protein carbonyl formation between groups, in the ipsilateral or contralateral hemispheres, at 6 hours and at 24 hours. These results indicate that hyperoxia treatment during focal cerebral ischemia—reperfusion is neuroprotective, and does not increase oxidative stress.
Imaging the GABA-Benzodiazepine Receptor Subtype Containing the α5-Subunit In Vivo with [11C]Ro15 4513 Positron Emission Tomography
Authors: Lingford-Hughes Anne , Hume Susan P. , Feeney Adrian , Hirani Ella , Osman Safiye , Cunningham Vincent J. , Pike Victor W. , Brooks David J. , Nutt David J.
Published: November 2003

There is evidence of marked variation in the brain distribution of specific subtypes of the GABA-benzodiazepine receptor and that particular subtypes mediate different functions. The α5-containing subtype is highly expressed in the hippocampus, and selective α5 inverse agonists (which decrease tonic GABA inhibition) are being developed as potential memory-enhancing agents. Evidence for such receptor localization and specialization in humans in vivo is lacking because the widely used probes for imaging the GABA-benzodiazepine receptors, [11C]flumazenil and [123I]iomazenil, appear to reflect binding to the α1 subtype, based on its distribution and affinity of flumazenil for this subtype. The authors characterized for positron emission tomography (PET) a radioligand from Ro15 4513, the binding of which has a marked limbic distribution in the rat and human brain in vivo. Competition studies in vivo in the rat revealed that radiolabeled Ro15 4513 uptake was reduced to nonspecific levels only by drugs that have affinity for the α5 subtype (flunitrazepam, RY80, Ro15 4513, L655,708), but not by the α1 selective agonist, zolpidem. Quantification of [11C]Ro15 4513 PET was performed in humans using a metabolite-corrected plasma input function. [11C]Ro15 4513 uptake was relatively greater in limbic areas compared with [11C]flumazenil, but lower in the occipital cortex and cerebellum. The authors conclude that [11C]Ro15 4513 PET labels in vivo the GABA-benzodiazepine receptor containing the α5 subtype in limbic structures and can be used to further explore the functional role of this subtype in humans.
In Vivo Magnetic Resonance Tracking of Magnetically Labeled Cells after Transplantation
Authors: Bulte Jeff W. M. , Duncan Ian D. , Frank Joseph A.
Published: November 2003

During the last few years, the therapeutic use of stem and progenitor cells as a substitute for malfunctioning endogenous cell populations has received considerable attention. Unlike their current use in animal models, the introduction of therapeutic cells in patients will require techniques that can monitor their tissue biodistribution noninvasively. Among the different imaging modalities, magnetic resonance (MR) imaging offers both near-cellular (i.e., 25- to 50-μ) resolution and whole-body imaging capability. In order to be visualized, cells must be labeled with an intracellular tracer molecule that can be detected by MR imaging. Methods have now been developed that make it possible to incorporate sufficient amounts of superparamagnetic iron oxide into cells, enabling their detection in vivo using MR imaging. This is illustrated for (neural stem cell—derived) magnetically labeled oligodendroglial progenitors, transplanted in the central nervous system of dysmyelinated rats. Cells can be followed in vivo for at least 6 weeks after transplantation, with a good histopathologic correlation including the formation of myelin. Now that MR tracking of magnetically labeled cells appears feasible, it is anticipated that this technique may ultimately become an important tool for monitoring the efficacy of clinical (stem) cell transplantation protocols.
Persistent Phosphorylation of Synaptic Proteins following Middle Cerebral Artery Occlusion
Authors: Matsumoto Shohei , Shamloo Mehrdad , Isshiki Atsushi , Wieloch Tadeusz
Published: November 2003

Transient cerebral ischemia following 1 to 2 hours of middle cerebral artery occlusion (MCAO) in the rat leads to infarction, which can be diminished by synaptic transmission modulators, implying aberrant cell signaling in the pathogenetic process. The authors report here changes in the levels of tyrosine phosphorylated proteins (PTyr) and calcium calmodulin kinase II (CaMKII) phosphorylation of Thr 286, in synaptosomal, particulate, and cytosolic fractions of different cortical areas following 1 or 2 hours of MCAO, or 2 hours of MCAO followed by 2 hours of reperfusion. At the end of 2-hour MCAO, PTyr, and in particular the pp180, indicative of NR2A/B subunit, increased in the synaptosomal fraction in less ischemic areas while it decreased in more severe ischemic regions. During reperfusion, phosphorylation increased at least 2-fold in all reperfused areas. During 2 hours of MCAO, the phosphorylation of CaMKII increased 8- to 10-fold in the synaptosomal fraction in all ischemic brain regions. During reperfusion, the phospho-CaMKII levels remained elevated by approximately 300% compared with the contralateral hemisphere (control). There was no increase in phospho-CaMKII in the cytosolic fraction at any time during or following ischemia in any of the brain regions examined. The authors conclude that both tyrosine kinase coupled pathways, as well as CaMKII-mediated cellular processes associated with synaptic activity, are strongly activated during and particularly following MCAO. These results support the hypothesis that aberrant cell signaling may contribute to ischemic cell death and dysfunction, and that selective modulators of cell signaling may be targets for pharmacological intervention against ischemic brain damage.
Comparative Study of Two Systems of Delivering Supplemental Protein With Standardized Tube Feedings
Authors: Luther Heidi , Barco Kathy , Chima Cinda , Yowler Charles J.
Published: November 2003

Burn patients often require protein supplementation for their nutritional support. Although these are often added to a commercial formula, published standards recommend a 4-hr hang time for manipulated open-system formulas in comparison with 24 hr for unopened closed systems. We hypothesized that use of standard closed-system formulas with the addition of protein flushes via the feeding tube twice daily would reduce nursing time and increase satisfaction. A pilot study included a time study comparing the two methods and a nursing satisfaction questionnaire. Management of an open system consistent with national standards took almost twice as much nursing time daily as the closed system with supplemental protein flushes (36.6 ± 17.1 min vs 18.6 ± 3.6 min;P = .051). Sixteen of 17 nurses preferred the closed system with protein flush. The results of this study were used to support expansion of the protocol change throughout the hospital.
Burns in Southern Turkey: Electrical Burns Remain a Major Problem
Authors: Nursal T. Z. , Yildirim S. , Tarim A. , Caliskan K. , Ezer A. , Noyan T.
Published: November 2003

In Turkey, burns represent a relatively small number of injuries overall, but they continue to be a major public health problem. Our aim in this study was to identify risk factors that affect outcome in burn patients hospitalized in the southern part of our country, with special emphasis on electrical burns. The database for 109 burn patients who were admitted to our burn center from April, 2000, through August, 2001, was retrospectively analyzed. Electrical injury was the cause of burn in 23 (21%) of the 109 cases. The burn causes differed among age groups and between the sexes, with males constituting 95% of the electrical burn patients. The mortality rate for the electrical burn group was lower than the rate for the rest of the burn patients (1/23 vs 17/86, respectively; P < .001); however, the opposite was true for complication rate (10/23 vs 5/86, respectively; P < .001), cost of treatment ($US 8351 vs $US 5122, respectively; P = .009), and length of hospital stay (39.9 vs 26.2 days, respectively; P < 0.001). The rate of electrical burn injury in Turkey has changed very little in the past two decades. This underlines the need for stronger efforts aimed at prevention, such as better public education and strict regulations regarding the distribution and use of electricity.
Role of Thymus Oil in Burn Wound Healing
Authors: Dursun Nurcan , Liman Narin , Özyazgan İrfan , Güneş Işin , Saraymen Recep
Published: November 2003

Thymus oil and its components are becoming increasingly popular as naturally occurring antimicrobial and antioxidant agents. The real importance of thymus on nitric oxide (NO) is unknown. NO is an important mediator in numerous physiologic and pathophysiologic events. Stasis and thrombosis in burn wound can progress as a result of the release of local mediators. The implication of NO in burn injury is not well studied. In this study, we tried to determine the role of burn-induced NO and whether thymus oil plays a protective role after a thermal injury. Rats were divided into five groups. We topically applied thymus oil, olive oil, and silverdin and sulfadiazine on the rats, respectively, during a period of 21 days after they were burned while under anesthesia. The burned control group and nonburned control group did not receive any treatment. The results of this study show that NO was overproduced by thermal injury and decreased during the days after burn injury. The decrease in rats treated with thymus and sulfadiazine was higher than the others. These data indicate that thymus oil may serve as a protective agent to the damaged tissues by decreasing the NO level. Histologic examination results show that the formation of new tissue in rats receiving thymus oil was more than other burned groups, and this finding supports our hypothesis.
An Unusual Cause of Burn Injury: Skin Exposure to Monochloroacetic Acid
Authors: Pirson J. , Toussaint P. , Segers N.
Published: November 2003

Chemical burns can be complicated by the absorption of some of the toxic products through the skin and a subsequent systemic toxicity. We report here the case of a 3-year-old child who was accidentally exposed to monochloroacetic acid and sent to our burn unit with second-degree burn wounds. Regardless of the entry route, monochloroacetic is rapidly and very effectively absorbed and induces a severe toxic syndrome. In the case of skin resorption, the severity of the intoxication is directly related to the area of the contaminated skin contaminated with fatalities when the exposure level reaches more than 5% of the body surface. In the case of a chemical burn with a suspicion of systemic toxicity or in case of burn with an unusual product, the correct attitude is to contact a poison information center, to immediately wash the exposed skin, and to start treating the systemic toxicity as soon as possible. The availability of specific antidotes in the case of unusual poisoning can be a problem.
Effects of Enhanced Patient Education on Compliance With Silicone Gel Sheeting and Burn Scar Outcome: A Randomized Prospective Study
Authors: So Ken , Umraw Nisha , Scott Jeff , Campbell Kent , Musgrave Melinda , Cartotto Robert
Published: November 2003

The purpose of this study was to determine whether enhanced patient education increases compliance with silicone gel sheeting (SGS) on hypertrophic (HT) scars and to determine whether this results in any improvement in scar outcome. Outpatients with a HT burn scar were randomized to either a conventional education group (CEG), which received routine instruction on the use of SGS or to an enhanced education Group (EEG), which also received routine instruction, along with a detailed 5-page handout and a 26-minute videotape. The CEG (n = 12, 67% male, age 38 ± 10 years) and the EEG (n = 13, 77% male, age 47 ± 10 years) were followed monthly for 6 months. Subjects in the EEG wore SGS for 21.8 ± 3.0 hr/day compared with only 10.1 ± 7.5 hr/day of use in the CEG (P < .001). Scars in the EEG had significantly better Vancouver Scar Scale ratings for pigmentation (P = .02), height (P = .03), and pliability (P = .02) by 6 months. Patients in the EEG had significantly better subjective ratings for the parameters of scar itch (P = .01), color (P = .02), hardness (P = .01), and elevation (P = .01). Finally, scars in the EEG had significantly better ratings for border height (P = .002) and thickness (P = .01) at 6 months based on evaluation of digital photographs. Detailed multimedia patient education improves compliance with SGS and results in a better scar outcome.
A Thirty-Year Review of Oral Appliances Used to Manage Microstomia, 1972 to 2002
Authors: Dougherty M. E. , Warden G. D.
Published: November 2003

Patients who have sustained a facial burn often contend with cosmetic and functional challenges, including microstomia. Many devices have been created by a variety of professionals to provide oral stretching. These devices can be classified as intraoral or extraoral and deliver a stretch either horizontally, vertically, or circumorally. The purpose of this article is to present a comprehensive review of oral-stretching devices.
Home Oxygen Therapy: Adjunct or Risk Factor?
Authors: Robb Bruce W. , Hungness Eric S. , Hershko Dan D. , Warden Glenn D. , Kagan Richard J.
Published: November 2003

The use of home oxygen therapy has become increasingly commonplace and is frequently prescribed by medical specialists. In this study, we have identified a generally unexpected risk of home oxygen therapy. We performed a retrospective review of 3673 consecutive patients treated at our adult burn center over a 10-year period from 1992 to 2001. We identified 27 patients with burns directly attributable to oxygen therapy and also noted an increased incidence of these injuries over the study period. The average age of the patients was 68.1 ± 9.2 years (range, 40–82 years). Twenty-three were using oxygen at home, three in nursing homes, and one was an inpatient in an acute care facility. Twenty-five patients (93%) were receiving oxygen therapy for the diagnosis of chronic obstructive pulmonary disease. Twenty-four patients (89%) were smoking while using oxygen, two were lighting pilot lights, and one was lighting his wife's cigarette. Four patients (15%) sustained burns greater than 10% TBSA. Seventeen patients (63%) had only partial thickness burns. Thirteen patients (48%) required admission for treatment of their burn injuries. The average length of stay for those admitted was 4.4 days. The average hospital charge for admitted patients was $8055. There were four deaths (15%), all of which were correlated only with the extent of injury. Although intuitively obvious to most health care professionals, not all patients understand that oxygen therapy and cigarettes or open flame can result in a significant injury. Although some practitioners have advocated not prescribing home oxygen for those who continue to smoke, an alternative means of reducing the incidence of this preventable complication appears warranted. Prevention efforts should focus on the counseling of patients and their caregivers as well as educating primary care physicians, nurses, and home health providers as to the dangers of oxygen use.
The Hemodynamic Impulse Response to a Single Neural Event
Authors: Martindale John , Mayhew John , Berwick Jason , Jones Myles , Martin Chris , Johnston Dave , Redgrave Peter , Zheng Ying
Published: November 2003

This article investigates the relation between stimulus-evoked neural activity and cerebral hemodynamics. Specifically, the hypothesis is tested that hemodynamic responses can be modeled as a linear convolution of experimentally obtained measures of neural activity with a suitable hemodynamic impulse response function. To obtain a range of neural and hemodynamic responses, rat whisker pad was stimulated using brief (≤2 seconds) electrical stimuli consisting of single pulses (0.3 millisecond, 1.2 mA) combined both at different frequencies and in a paired-pulse design. Hemodynamic responses were measured using concurrent optical imaging spectroscopy and laser Doppler flowmetry, whereas neural responses were assessed through current source density analysis of multielectrode recordings from a single barrel. General linear modeling was used to deconvolve the hemodynamic impulse response to a single “neural event” from the hemodynamic and neural responses to stimulation. The model provided an excellent fit to the empirical data. The implications of these results for modeling schemes and for physiologic systems coupling neural and hemodynamic activity are discussed.
Mild Hypothermia Inhibits Nuclear Factor-κB Translocation in Experimental Stroke
Authors: Han Hyung Soo , Karabiyikoglu Murat , Kelly Stephen , Sobel Raymond A. , Yenari Midori A.
Published: November 2003

Nuclear factor-κB (NFκB) is a transcription factor that is activated after cerebral ischemia. NFκB activation leads to the expression of many inflammatory genes involved in the pathogenesis of stroke. The authors previously showed that mild hypothermia is protective even when cooling begins 2 h after stroke onset. In the present study, they examined the influence of hypothermia on NFκB activation. Rats underwent 2 h of transient middle cerebral artery occlusion. Brains were cooled to 33°C immediately after or 2 h after occlusion, and maintained for 2 h. After normothermic ischemia (brain temperature at 38°C), NFκB cytoplasmic expression, nuclear translocation, and binding activity were observed as early as 2 h in the ischemic hemisphere and persisted at 24 h. Hypothermia decreased NFκB translocation and binding activity but did not alter overall expression. Hypothermia also affected the levels of NFκB regulatory proteins by suppressing phosphorylation of NFκB's inhibitory protein (IκB-α) and IκB kinase (IKK-γ) and decreasing IKK activity, but did not alter overall IKK levels. Hypothermia suppressed the expression of two NFκB target genes: inducible nitric oxide synthase and TNF-α. These data suggest that the protective effect of hypothermia on cerebral injury is, in part, related to NFκB inhibition due to decreased activity of IKK.
Relation between Relative Cerebral Blood Flow, Relative Cerebral Blood Volume, and Mean Transit Time in Patients with Acute Ischemic Stroke Determined by Perfusion-Weighted MRI
Authors: Singer Oliver C. , de Rochemont Richard du Mesnil , Foerch Christian , Stengel Astrid , Lanfermann Heiner , Sitzer Matthias , Neumann-Haefelin Tobias
Published: November 2003

The relation between relative cerebral blood flow (relCBF), relative cerebral blood volume (relCBV), and mean transit time (MTT) changes was examined in 20 patients with acute cerebral ischemia (<6 h) using perfusion-weighted magnetic resonance imaging. Regions of interest (ROI) were selected on MTT maps covering the entire MTT abnormal cortical area. These ROIs were transferred to the relCBF and relCBV maps to analyze the relation between relCBF, relCBV, and MTT on a voxel-by-voxel basis. On the unaffected side, a tight coupling of relCBF and relCBV was found with little variation of MTT. In hypoperfused cortex, relCBV was increased at all investigated relCBF categories, and there was greater relCBV variability than on the unaffected side. Only a severe decrease of relCBF, to less than 0.3, in comparison with the unaffected side was associated with a reduction of relCBV less than 1.0. In contrast to the unaffected side, a power law function (relCBV = 2.283 × relCBF0.549) resulted in a better fit than using a linear function for the correlation of relCBF and relCBV. MTT ratios increased steadily with decreasing CBF values. In conclusion, there is a clear relation between different perfusion-weighted magnetic resonance imaging parameters in acute ischemia, reflecting both the degree of hemodynamic failure as well as compensatory mechanisms including vasodilation.
Comparative Study of the FAIR Technique of Perfusion Quantification with the Hydrogen Clearance Method
Authors: Pell Gaby S. , King Martin D. , Proctor Edward , Thomas David L. , Lythgoe Mark F. , Gadian David G. , Ordidge Roger J.
Published: November 2003

Arterial spin labeling magnetic resonance methods, including flow-sensitive alternating inversion recovery (FAIR), are becoming increasingly common for the noninvasive quantification of cerebral blood flow (CBF). This report compares the FAIR method with hydrogen clearance. The latter is an established, invasive technique for CBF measurement in animals. Paired readings of CBF were obtained in gerbils to maximize the degree of spatial and temporal correspondence between methods. Flow-sensitive alternating inversion recovery (50 averages, 6.7-minute measurement time) and hydrogen clearance measurements were made concurrently. Cerebral blood flow values measured by both techniques displayed an initial decrease because of the injurious effects of electrode insertion and subsequent recovery. Mixed model regression analysis, structural equations modeling, and a simple concordance correlation coefficient analysis were performed. No evidence of a marked systematic bias in the FAIR measurements was found; mixed model regression analysis yielded relative bias estimates of 0.4 (confidence interval: 3.0, 3.9) mL · 100 g−1 · min−1 and −3.7 (−12.1, 4.7) mL · 100 g−1 · min−1 at 20 and 100 mL · 100 g−1 · min−1, respectively. The principal limitation of the FAIR technique was the magnitude of the random measurement error (imprecision), which had a standard deviation on the order of 10 mL · 100 g−1 · min−1.
Lactate: A Preferred Fuel for Human Brain Metabolism in Vivo
Authors: Smith Diarmuid , Pernet Andrew , Hallett William A. , Bingham Emma , Marsden Paul K. , Amiel Stephanie A.
Published: November 2003

Recent in vitro studies suggest that lactate, rather than glucose, may be the preferred fuel for neuronal metabolism. The authors examined the effect of lactate on global brain glucose uptake in euglycemic human subjects using 18fluorodeoxyglucose (FDG) positron emission tomography (PET). Eight healthy men, aged 40 to 54 years, underwent a 60-minute FDG-PET scan on two occasions in random order. On one occasion, 6.72% sodium lactate was infused at a rate of 50 μmol · kg−1 · min−1 for 20 minutes and then reduced to 30 μmol · kg−1 · min−1; 1.4% sodium bicarbonate was infused as a control on the other occasion. Plasma glucose levels were not different between the two groups (5.3 ± 0.23 and 5.3 ± 0.24 mmol/L, P = 0.55). Plasma lactate was significantly elevated by lactate infusion (4.08 ± 0.35 vs. 0.63 ± 0.22 mmol/L, P < 0.0005. The whole-brain rate of glucose uptake was significantly reduced by approximately 17% during lactate infusion (0.195 ± 0.022 vs. 0.234 ± 0.020 μmol · g−1 · min−1, P = 0.001). The authors conclude that, in vivo in humans, circulating lactate is used by the brain at euglycemia, with sparing of glucose.
Temporal Relation between the ADC and DC Potential Responses to Transient Focal Ischemia in the Rat: A Markov Chain Monte Carlo Simulation Analysis
Authors: King Martin D. , Crowder Martin J. , Hand David J. , Harris Neil G. , Williams Stephen R. , Obrenovitch Tihomir P. , Gadian David G.
Published: November 2003

Markov chain Monte Carlo simulation was used in a reanalysis of the longitudinal data obtained by Harris et al. ( J Cereb Blood Flow Metab 20:28–36) in a study of the direct current (DC) potential and apparent diffusion coefficient (ADC) responses to focal ischemia. The main purpose was to provide a formal analysis of the temporal relationship between the ADC and DC responses, to explore the possible involvement of a common latent (driving) process. A Bayesian nonlinear hierarchical random coefficients model was adopted. DC and ADC transition parameter posterior probability distributions were generated using three parallel Markov chains created using the Metropolis algorithm. Particular attention was paid to the within-subject differences between the DC and ADC time course characteristics. The results show that the DC response is biphasic, whereas the ADC exhibits monophasic behavior, and that the two DC components are each distinguishable from the ADC response in their time dependencies. The DC and ADC changes are not, therefore, driven by a common latent process. This work demonstrates a general analytical approach to the multivariate, longitudinal data-processing problem that commonly arises in stroke and other biomedical research.
Insulin-Like Growth Factor (IGF)-1 Suppresses Oligodendrocyte Caspase-3 Activation and Increases Glial Proliferation after Ischemia in Near-Term Fetal Sheep
Authors: Cao Yun , Gunn Alistair Jan , Bennet Laura , Wu David , George Sherly , Gluckman Peter D. , Shao Xiao-Mei , Guan Jian
Published: November 2003

Insulin-like growth factor (IGF-1) markedly increases myelination and glial numbers in white matter after ischemia in near-term fetal sheep; however, it is unclear whether this is due to reduced cell loss or increased secondary proliferation. Brain injury was induced in near-term fetal sheep by 30 minutes of bilateral carotid artery occlusion. Ninety minutes after the occlusion, fetuses were given, intracerebroventricularly, either a single dose of IGF-1 (either 3 or 30 μg), or 3 μg followed by 3 μg over 24 hours (3 + 3 μg). White matter was assessed 4 days after reperfusion. Three micrograms, but not 30 μg of IGF-1 prevented loss of oligodendrocytes and myelin basic protein density ( P < 0.001) compared to the vehicle-treated ischemia controls. No additional effect was observed in the 3 + 3 μg group. IGF-1 treatment was associated with reduced caspase-3 activation and increased glial proliferation in a similar dose-dependent manner. Caspase-3 was only expressed in oligodendrocytes that showed apoptotic morphology. Proliferating cell nuclear antigen co-localized with both oligodendrocytes and astrocytes and microglia. Thus, increased oligodendrocyte numbers after IGF-1 treatment is partly due to suppression of apoptosis, and partly to increased proliferation. In contrast, the increase in reactive glia was related only to proliferation. Speculatively, reactive glia may partly mediate IGF-1 white matter protection.
Ultrasonographic Assessment of Global Cerebral Blood Volume in Healthy Adults
Authors: Doepp Florian , Schreiber Stephan J , Brunecker Peter , Valdueza José M
Published: November 2003

The authors describe a new ultrasonographic method for analysis of global cerebral blood volume (CBV) and its application under controlled hyperventilation. CBV was determined as the product of global cerebral blood flow volume (CBF) and global cerebral circulation time. CBF was measured by duplex sonography and calculated as the sum of flow volumes in both internal carotid arteries and vertebral arteries. Extracranial Doppler assessed cerebral circulation time by determining the time interval of echo-contrast bolus arrival between internal carotid artery and contralateral internal jugular vein. Forty-four healthy volunteers (mean age 45 ± 19 years, range 20–79 years) were studied. Mean CBV was 77 ± 13 mL. CBV did not correlate with age, end-tidal carbon dioxide level, heart rate, or blood pressure. Hypocapnia was induced in 10 subjects by controlled hyperventilation. Mean reduction of end-tidal carbon dioxide values by 9 ± 1 mm Hg led to a significant increase in cerebral circulation time (6.1 ± 0.9 to 8.4 ± 1.1 second, P < 0.0001) and a significant CBF decrease (742 ± 85 to 526 ± 77 mL/min, P < 0.0001), whereas CBV remained unchanged (75 ± 6 to 73 ± 10 mL).
Overexpression of Monocyte Chemoattractant Protein 1 in the Brain Exacerbates Ischemic Brain Injury and is Associated with Recruitment of Inflammatory Cells
Authors: Chen Yong , Hallenbeck John M. , Ruetzler Christl , Bol David , Thomas Karen , Berman Nancy E. J. , Vogel Stefanie N.
Published: November 2003

Brain cells produce cytokines and chemokines during the inflammatory process after stroke both in animal models and in patients. Monocyte chemoattractant protein 1 (MCP-1), one of the proinflammatory chemokines, can attract monocytes to the tissue where MCP-1 is overexpressed. However, the role of MCP-1 elevation in stroke has not been explored in detail. The authors hypothesized that elevated MCP-1 levels would lead to increased influx of monocytes and increased brain infarction size in stroke induced by middle cerebral artery occlusion with partial reperfusion. There were no differences in blood pressure, blood flow, or vascular architecture between wild-type mice and transgenic MBP-JE mice. Twenty-four to 48 hours after middle cerebral artery occlusion, brain infarction volumes after ischemia were significantly larger in MBP-JE mice than in wild-type controls and were accompanied by increased local transmigration and perivascular accumulation of macrophages and neutrophils. These results indicate that MCP-1 can contribute to inflammatory injury in stroke.
Correlation between Delayed Neuronal Cell Death and Selective Decrease in Phosphatidylinositol 4-Kinase Expression in the CA1 Subfield of the Hippocampus after Transient Forebrain Ischemia
Authors: Furuta Yudai , Uehara Takashi , Nomura Yasuyuki
Published: November 2003

Transient forebrain ischemia induces a delayed neuronal death in the CA1 area of the hippocampus. However, the mechanism leading to this phenomenon has yet to be established. The authors used an mRNA differential-display method to isolate genes for which mRNA levels change only in the hippocampus during ischemia/reperfusion. They succeeded in identifying the product of one down-regulated gene as phosphatidylinositol 4-kinase (PI 4-K). Compared with control levels, PI 4-K mRNA expression in the hippocampus, but not the cerebral cortex, was significantly decreased by 30% and about 80% 1 and 7 days after ischemia/reperfusion, respectively. Interestingly, PI 4-K and PI bisphosphate levels were selectively decreased in the CA1 region, but not other regions, whereas TUNEL-positive cells could be detected 3 days after ischemia. Consistent with these results, PI 4-K expression was suppressed by hypoxia in SK-N-MC neuroblastoma cells before loss of cell viability. Overexpression of wild-type PI 4-K, but not the kinase-negative mutant of PI 4-K (K1789A), recovered the loss of viability induced by hypoxia. These findings strongly suggest that a prior decrease in PI 4-K and PI bisphosphate levels caused by brain ischemia/hypoxia is partly involved in delayed neuronal cell death.
Metabolic, Neurochemical, and Histologic Responses to Vibrissa Motor Cortex Stimulation after Traumatic Brain Injury
Authors: Ip Emily Y , Zanier Elisa Roncati , Moore Amy H , Lee Stefan M , Hovda David A
Published: November 2003

During the prolonged metabolic depression after traumatic brain injury (TBI), neurons are less able to respond metabolically to peripheral stimulation. Because this decreased responsiveness has been attributed to circuit dysfunction, the present study examined the metabolic, neurochemical, and histologic responses to direct cortical stimulation after lateral fluid percussion injury (LFPI). This study addressed three specific hypotheses: that neurons, if activated after LFPI, will increase their utilization of glucose even during a period of posttraumatic metabolic depression; that this secondary activation results in an increase in the production of lactate and a depletion of extracellular glucose; and that because cells are known to be in a state of energy crisis after traumatic brain injury, additional energy demands resulting from activation can result in their death. The results indicate that stimulating to levels eliciting a vibrissa twitch resulted in an increase in the cerebral metabolic rate for glucose (CMRglc; μmol·100 g−1·min−1) of 34% to 61% in the sham-operated, 1-hour LFPI, and 7-day LFPI groups. However, in the 1-day LFPI group, stimulation induced a 161% increase in CMRglc and a 35% decrease in metabolic activation volume. Extracellular lactate concentrations during stimulation significantly increased from 23% in the sham-injured group to 55% to 63% in the 1-day and 7-day LFPI groups. Extracellular glucose concentrations during stimulation remained unchanged in the sham-injured and 7-day LFPI groups, but decreased 17% in the 1-day LFPI group. The extent of cortical degeneration around the stimulating electrode in the 1-day LFPI group nearly doubled when compared with controls. These results indicate that at 1 day after LFPI, the cortex can respond to stimulation with an increase in anaerobic glycolysis; however, this metabolic response to levels eliciting a vibrissa response via direct cortical stimulation appears to constitute a secondary injury in the TBI brain.
Diffuse Optical Tomography of Cerebral Blood Flow, Oxygenation, and Metabolism in Rat during Focal Ischemia
Authors: Culver Joseph P , Durduran Turgut , Furuya Daisuke , Cheung Cecil , Greenberg Joel H , Yodh A G
Published: November 2003

Diffuse optical tomography (DOT) is an attractive approach for evaluating stroke physiology. It provides hemodynamic and metabolic imaging with unique potential for continuous noninvasive bedside imaging in humans. To date there have been few quantitative spatial-temporal studies of stroke pathophysiology based on diffuse optical signatures. The authors report DOT images of hemodynamic and metabolic contrasts using a rat middle cerebral artery occlusion (MCAO) stroke model. This study used a novel DOT device that concurrently obtains coregistered images of relative cerebral blood volume (rCBV), tissue-averaged hemoglobin oxygen saturation (Sto2), and relative cerebral blood flow (rCBF). The authors demonstrate how these hemodynamic measures can be synthesized to calculate an index of the oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen consumption (CMRo2). Temporary (60-minute) MCAO was performed on five rats. Ischemic changes, averaged over the 60 minutes of occlusion, were as follows: rCBF = 0.42 ± 0.04, rCBV = 1.02 ± 0.04, ΔSto2 = −11 ± 2%, rOEF = 1.39 ± 0.06 and rCMRo2 = 0.59 ± 0.07. Although rOEF increased in response to decreased blood flow, rCMRo2 decreased. The sensitivity of this method of DOT analysis is discussed in terms of assumptions about baseline physiology, and the diffuse optical results are compared with positron emission tomography, magnetic resonance imaging, and histology observations in the literature.
Metabolic Imaging of Human Cognition: An fMRI/1H-MRS Study of Brain Lactate Response to Silent Word Generation
Authors: Urrila Anna S , Hakkarainen Antti , Heikkinen Sami , Vuori Kim , Stenberg Dag , Häkkinen Anna-Maija , Lundbom Nina , Porkka-Heiskanen Tarja
Published: November 2003

Proton magnetic resonance spectroscopy (1H-MRS) allows in vivo assessment of the metabolism related to human brain functions. Visual, auditory, tactile, and motor stimuli induce a temporary increase in the brain lactate level, which may act as a rapid source of energy for the activated neurons. The authors studied the metabolism of the frontal lobes during cognitive stimulation and measured local lactate levels with standard 1H-MRS, after localizing the activated area by functional MRI. Lactate levels were monitored while the subjects either silently listed numbers (baseline) or performed a silent word-generation task (stimulus-activation). The cognitive stimulus-activation produced a 50% increase in the brain lactate level in the left inferior frontal gyrus. The results show that metabolic imaging of neuronal activity related to cognition is possible using 1H-MRS.
Neuroprotective Effect of Postischemic Administration of Sodium Orthovanadate in Rats with Transient Middle Cerebral Artery Occlusion
Authors: Hasegawa Yu , Hamada Jun-ichiro , Morioka Motohiro , Yano Shigetoshi , Kawano Takayuki , Kai Yutaka , Fukunaga Kohji , Ushio Yukitaka
Published: November 2003

Orthovanadate is a competitive inhibitor of protein tyrosine phosphatases. Some of its reported biologic effects are its insulin mimetic property and its activation of phosphoinositide 3-kinase and extracellular-signal regulated kinase (ERK). The authors previously reported its neuroprotective effect on delayed neuronal death of gerbil hippocampal CA1 neurons via Akt and ERK activation after transient forebrain ischemia. In the present study, the neuroprotective effect of postischemic intraperitoneal administration of sodium orthovanadate (2 mL/kg of 50-mmol/L sodium orthovanadate in saline) was investigated in rats with transient middle cerebral artery occlusion. Ischemic neuronal injury was evaluated 1 day and 28 days after ischemia. The neuroprotective effect of orthovanadate was significant in the cortex but not the caudate putamen (ischemic core) at both 1 and 28 days after ischemia. In orthovanadate group, the activities of Akt and ERK were maintained after reperfusion; they were decreased in saline group. Blood glucose level decreased but within normal range. Regional cerebral blood flow was lower than that of saline group only at 0 hours after reperfusion. These data suggest that orthovanadate has neuroprotective effects in rats with transient middle cerebral artery occlusion and that these effects are mediated by Akt and ERK activation. Furthermore, low blood glucose levels and gradual recovery of regional cerebral blood flow may contribute to neuroprotection.
Tacrolimus, a Potential Neuroprotective Agent, Ameliorates Ischemic Brain Damage and Neurologic Deficits after Focal Cerebral Ischemia in Nonhuman Primates
Authors: Furuichi Yasuhisa , Maeda Masashi , Moriguchi Akira , Sawamoto Taiji , Kawamura Akio , Matsuoka Nobuya , Mutoh Seitaro , Yanagihara Takehiko
Published: November 2003

Tacrolimus (FK506), an immunosuppressive drug, is known to have potent neuroprotective activity and attenuate cerebral infarction in experimental models of stroke. Here we assess the neuroprotective efficacy of tacrolimus in a nonhuman primate model of stroke, photochemically induced thrombotic occlusion of the middle cerebral artery (MCA) in cynomolgus monkeys. In the first experiment, tacrolimus (0.01, 0.032, or 0.1 mg/kg) was intravenously administered immediately after MCA occlusion, and neurologic deficits and cerebral infarction volumes were assessed 24 hours after the ischemic insult. Tacrolimus dose-dependently reduced neurologic deficits and infarction volume in the cerebral cortex, with statistically significant amelioration of neurologic deficits at 0.032 and 0.1 mg/kg and significant reduction of infarction at 0.1 mg/kg. In the second experiment, the long-term efficacy of tacrolimus on neurologic deficits and cerebral infarction was assessed. Vehicle-treated monkeys exhibited persistent and severe deficits in motor and sensory function for up to 28 days. A single intravenous bolus injection of tacrolimus (0.1 or 0.2 mg/kg) produced long-lasting amelioration of neurologic deficits and significant reduction of infarction volume. In conclusion, we have provided compelling evidence that a single dose of tacrolimus not only reduces brain infarction but also ameliorates long-term neurologic deficits in a nonhuman primate model of stroke, strengthening the view that tacrolimus might be beneficial in treating stroke patients.
Lactate is a Preferential Oxidative Energy Substrate over Glucose for Neurons in Culture
Authors: Bouzier-Sore Anne-Karine , Voisin Pierre , Canioni Paul , Magistretti Pierre J , Pellerin Luc
Published: November 2003

The authors investigated concomitant lactate and glucose metabolism in primary neuronal cultures using 13C- and 1H-NMR spectroscopy. Neurons were incubated in a medium containing either [1-13C]glucose and different unlabeled lactate concentrations, or unlabeled glucose and different [3-13C]lactate concentrations. Overall, 13C-NMR spectra of cellular extracts showed that more 13C was incorporated into glutamate when lactate was the enriched substrate. Glutamate 13C-enrichment was also found to be much higher in lactate-labeled than in glucose-labeled conditions. When glucose and lactate concentrations were identical (5.5 mmol/L), relative contributions of glucose and lactate to neuronal oxidative metabolism amounted to 21% and 79%, respectively. Results clearly indicate that when neurons are in the presence of both glucose and lactate, they preferentially use lactate as their main oxidative substrate.
Empirical modelling of bank market exclusion
Authors: Sharma Pramendra , Reddy Mahendra
Published: November 2003

Driven by higher profit incentives, banks’ marketing strategies have tended increasingly to exclude sections of the retail market on socio‐economic lines. Ironically, these strategies are now seen to have profitability and social responsibility implications. Little previous attempt has been made to quantify the relationship between bank service access and the determinants that act as deterrents, to improve general understanding of the extent of exclusionary influence of each determinant and the relevant implications. This study examines quantified relationships using the Probit model and data collected through primary research from a developing economy in the Asia Pacific region. Results show that bank‐driven pricing strategies may have an overriding effect on other factors. The analysis demonstrates that profits may be increased, socio‐economic exclusionary effects reduced and social image improved by voluntarily reconsidering pricing and other bank‐driven exclusionary strategies.
Barriers to Internet banking adoption: a qualitative study among corporate customers in Thailand
Authors: Rotchanakitumnuai Siriluck , Speece Mark
Published: November 2003

Many Thai banks are currently implementing Internet banking. Banks that offer service via this channel claim that it reduces costs and makes them more competitive. However, many corporate customers are not highly enthusiastic about Internet banking. An understanding of why corporate customers do not accept Internet banking can assist banks to implement this self‐service technology more efficiently. In‐depth qualitative interviews with Thai firms suggest that security of the Internet is a major factor inhibiting wider adoption. Those already using Internet banking seem to have more confidence that the system is reliable, whereas non‐users are much more service conscious, and do not trust financial transactions made via Internet channels. Non‐Internet banking users tend to have more negative management attitudes toward adoption and are more likely to claim lack of resources. Legal support is also a major barrier to Internet banking adoption for corporate customers.
The Chinese payment card market: an exploratory study
Authors: Worthington Steve
Published: November 2003

The article is based on both secondary and primary research into the use of plastic payment cards in China. The secondary research offers an understanding of the history and current situation of payment cards in China, whilst the primary research provides insights into the uniqueness of the Chinese market from the perspective of card holders, card issuers and merchant acceptors. As barriers to entry into China remain high for foreign banks, particularly if they wish to pursue a branch centric approach to distribution, the article also draws attention to the advantages of a card centric approach to market entry. Other Asia‐Pacific markets such as Australia, Hong Kong, Korea and Japan have already embraced the plastic card as a means of payment at the point‐of‐sale. As a market, China has more potential than any other country in Asia‐Pacific, but more knowledge is required concerning the evolution to date of payment cards in China and the impediments that foreign entrants will face.
Relationship marketing: customer commitment and trust as a strategy for the smaller Hong Kong corporate banking sector
Authors: Adamson Ivana , Chan Kok‐Mun , Handford Donna
Published: November 2003

After the Chinese takeover of Hong Kong its smaller banks carved out a niche for themselves in the corporate market by embracing relationship marketing as a way of doing business. Examines the commitment‐trust dimension of the relationship marketing paradigm in the Hong Kong’s corporate banking sector. The findings show that the Hong Kong banks’ marketing strategy and a long‐term orientation were positively correlated with customer commitment and trust; communications and relational norms were positively correlated with trust; relationship benefits were positively correlated with customer commitment; and the banks’ reputation was negatively correlated with trust and commitment. To continue to be successful in the corporate sector, smaller banks must invest in the long‐term relationship marketing infrastructures to support a customer‐oriented approach. To enhance the corporate customers’ confidence further, the banks must develop parallel communication channels with their customers, show flexibility in their dealings and maximize mutual relationship benefits by minimising drastic recovery actions.
Accelerated learning in new product development teams
Authors: Lynn Gary S. , Akgün Ali E. , Keskin Halit
Published: November 2003

Learning in new‐product development teams is cited as being vital in today's competitive, uncertain, and turbulent environments. However, studies on accelerated learning in product‐development teams are, surprisingly, lacking. This study proposes a model for accelerated team learning in new‐product development based on constructs borrowed from accelerated learning models (or “suggestopedy”) in the individual learning scholarship. It is argued that fast‐learning teams launch new products more quickly, and with increased probability of success. Moreover, specific mechanisms to help teams learn more quickly are within the control of teams. These include vision clarity, learning from customers and competitors, information coding, top management support, past product review, aggressive deadlines and daily meetings.
The patterns of success in product development: a case study
Authors: Suomala Petri , Jokioinen Ilkka
Published: November 2003

Success in product development can be considered a general aim for any R&D activity. Unfortunately, success is very multidimensional. Which dimensions of success one should include and how one can measure these dimensions is an essential question that must be resolved within R&D management. The aim of the paper is to analyse the multidimensionality of success at R&D project level. Using the evidence from three industrial cases, the paper shows the versatility of the concept of success in product development. On the basis of the evidence, the paper concludes that there is often only a vague correlation between three aspects of R&D success – financial, technical and project management. The focus of the paper is on the development of investment goods for the paper industry.