bluuebunny/crossref_metadata_2025 huggingface dataset:
The Tibialis Anterior Muscle Flap for Full-Thickness Tibial Burns
Authors: Sood Rajiv , Ranieri Jaime , Murthy Vimal , Weber Karen
Published: November 2003

Full-thickness burn wounds to the tibia present a challenging coverage problem. If skin grafting fails, few local options exist, and free tissue transfer may be required for coverage. We report on the use of the tibialis anterior muscle flap to cover longitudinal tibial defects in five extremities in four patients. These patients sustained 80, 55, 40, and 11% total body surface area burns. Postoperatively, all five extremity wounds healed with full coverage of the tibia. Minimal deficits in ankle inversion and eversion resulted, but all patients are fully capable of walking and able to bear weight. We feel that the tibialis anterior muscle flap is a safe, reliable, technically simple alternative for coverage of the burned tibia.
Postburn Galactorrhea With Refractory Hypertrophic Scars: Role of Obesity Under Scrutiny
Authors: Saraiya Hemant
Published: November 2003

Postburn galactorrhea, although relatively uncommon, is a complex problem to treat. Three of 25 female premenopausal patients who were admitted during the years 1995 to 2001 with more than 40% TBSA burns developed this problem. All three patients were obese according to body mass index and other clinical criteria. It was observed that the additional disturbance of equilibrium of hypothalamus because of burn injury, which is already disturbed as per se in obese patients, precipitates sustained release of prolactin, leading to galactorrhea. Hyperinsulinemia because of obesity and associated reactive metabolic response of burn trauma contribute to the stimulation of prolactin secretion and sustained hyperprolactinemia. Interestingly, our patients who developed postburn galactorrhea also developed refractory hypertrophic scars not readily amenable to preventive and conservative therapeutic treatment methods. The responsible factor for its development can be a rise in prolactin levels with interplay of other hormones, such as melanocyte-stimulating hormone (MSH), from the anterior pituitary. Repeated serum prolactin measurements and early control of rising levels during the burn treatment, particularly in obese patients, are recommended. Early and vigorous measures to prevent scar hypertrophy also are advocated. In our study, we failed to correlate chest wall burns with galactorrhea.
Relation between Regional Functional MRI Activation and Vascular Reactivity to Carbon Dioxide during Normal Aging
Authors: Riecker Axel , Grodd Wolfgang , Klose Uwe , Schulz Jorg B. , Gröschel Klaus , Erb Michael , Ackermann Hermann , Kastrup Andreas
Published: November 2003

Recent blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging studies have shown a reduction of cerebral activation during aging, which may be associated with age-related changes of the cerebral vascular system. The authors used a global hypercapnic breath-holding challenge to define nonneuronal contributions to a significantly reduced activation in the primary sensorimotor cortex during finger tapping in a group of old (n = 6; mean age 65 years) compared with a group of young (n = 6; mean age 27 years) subjects. Within significantly activated voxels in both groups during finger tapping, the mean BOLD signal amplitudes were significantly smaller in the group of older subjects for both tasks. In those voxels showing significant activation only in young subjects during finger tapping, the response to hypercapnia was also greatly diminished in older subjects. The attenuated hypercapnic BOLD signal response in older subjects within this region suggests that age-dependent changes of the cerebral vasculature may alter the neuronal–vascular coupling. In older subjects, cerebral vessels may not react as effectively in response to a vasodilating stimulus, which will lead to differences in the number of voxels that pass a criterion threshold despite similar neuronal activation.
Deferoxamine Improves Early Postresuscitation Reperfusion after Prolonged Cardiac Arrest in Rats
Authors: Liachenko Serguei , Tang Pei , Xu Yan
Published: November 2003

The no-reflow phenomenon and delayed hypoperfusion after transient cardiac arrest (CA) impede postischemic recovery. Activation of lipid peroxidation (LPO) after ischemia and reperfusion is considered one of the mechanisms responsible for such abnormalities. The present study investigates the influence of iron-dependent LPO inhibitor deferoxamine (DFO) on the cerebral perfusion after prolonged CA and resuscitation. Fourteen male Sprague-Dawley rats were subjected to 17 minutes of CA, induced by esmolol (an ultrashort-acting β-blocker) and apnea, followed by resuscitation by retrograde intraaortic infusion of oxygenated donor blood mixed with a resuscitation cocktail inside a vertical-bore 9.4-T magnetic resonance imaging (MRI) magnet. Animals were randomized double-blindly into two groups to receive DFO or saline, respectively. Cerebral perfusion was measured by MRI continuously using the arterial spin-labeling method before, during, and after CA. All animals were successfully resuscitated in 1.36 ± 0.04 minutes with well-controlled arrest time (17.99 ± 0.03 minutes) in both groups. Deferoxamine significantly increased cerebral perfusion in hippocampus, thalamus, hypothalamus, and amygdala, but not in cortex, during the first 20 minutes of reperfusion. In the DFO-treated group, the neurologic deficit score was significantly better (400 ± 30 vs. 250 ± 47, out of 500 as the best, P < 0.05) and weight loss was significantly less (33 ± 6 vs. 71 ± 19 g, P < 0.05) 5 d after arrest. The finding supports the notion that early reperfusion immediately after resuscitation is important for long-term outcome and that LPO may be involved in microvascular disorders during the reperfusion, particularly in the brain after prolonged cardiac arrest and resuscitation.
Genomics of the Periinfarction Cortex after Focal Cerebral Ischemia
Authors: Lu Aigang , Tang Yang , Ran Ruiqiong , Clark Joseph F. , Aronow Bruce J. , Sharp Frank R.
Published: November 2003

Understanding transcriptional changes in brain after ischemia may provide therapeutic targets for treating stroke and promoting recovery. To study these changes on a genomic scale, oligonucleotide arrays were used to assess RNA samples from periinfarction cortex of adult Sprague-Dawley rats 24 h after permanent middle cerebral artery occlusions. Of the 328 regulated transcripts in ischemia compared with sham-operated animals, 264 were upregulated, 64 were downregulated, and 163 (49.7%) had not been reported in stroke. Of the functional groups modulated by ischemia: G-protein–related genes were the least reported; and cytokines, chemokines, stress proteins, and cell adhesion and immune molecules were the most highly expressed. Quantitative reverse transcription polymerase chain reaction of 20 selected genes at 2, 4, and 24 h after ischemia showed early upregulated genes (2 h) including Narp, Rad, G33A, HYCP2, Pim-3, Cpg21, JAK2, CELF, Tenascin, and DAF. Late upregulated genes (24 h) included Cathepsin C, Cip-26, Cystatin B, PHAS-I, TBFII, Spr, PRG1, and LPS-binding protein. Glycerol 3-phosphate dehydrogenase, which is involved in mitochondrial reoxidation of glycolysis derived NADH, was regulated more than 60-fold. Plasticity-related transcripts were regulated, including Narp, agrin, and Cpg21. A newly reported lung pathway was also regulated in ischemic brain: C/EBP induction of Egr-1 ( NGFI-A) with downstream induction of PAI-1, VEGF, ICAM, IL1, and MIP1. Genes regulated acutely after stroke may modulate cell survival and death; also, late regulated genes may be related to tissue repair and functional recovery.
Changes in Human Cerebral Blood Flow and Cerebral Blood Volume during Hypercapnia and Hypocapnia Measured by Positron Emission Tomography
Authors: Ito Hiroshi , Kanno Iwao , Ibaraki Masanobu , Hatazawa Jun , Miura Shuichi
Published: November 2003

Hypercapnia induces cerebral vasodilation and increases cerebral blood flow (CBF), and hypocapnia induces cerebral vasoconstriction and decreases CBF. The relation between changes in CBF and cerebral blood volume (CBV) during hypercapnia and hypocapnia in humans, however, is not clear. Both CBF and CBV were measured at rest and during hypercapnia and hypocapnia in nine healthy subjects by positron emission tomography. The vascular responses to hypercapnia in terms of CBF and CBV were 6.0 ± 2.6%/mm Hg and 1.8 ± 1.3%/mm Hg, respectively, and those to hypocapnia were −3.5 ± 0.6%/mm Hg and −1.3 ± 1.0%/mm Hg, respectively. The relation between CBF and CBV was CBV = 1.09 CBF0.29. The increase in CBF was greater than that in CBV during hypercapnia, indicating an increase in vascular blood velocity. The degree of decrease in CBF during hypocapnia was greater than that in CBV, indicating a decrease in vascular blood velocity. The relation between changes in CBF and CBV during hypercapnia was similar to that during neural activation; however, the relation during hypocapnia was different from that during neural deactivation observed in crossed cerebellar diaschisis. This suggests that augmentation of CBF and CBV might be governed by a similar microcirculatory mechanism between neural activation and hypercapnia, but diminution of CBF and CBV might be governed by a different mechanism between neural deactivation and hypocapnia.
Persistently Low Extracellular Glucose Correlates with Poor Outcome 6 Months after Human Traumatic Brain Injury despite a Lack of Increased Lactate: A Microdialysis Study
Authors: Vespa Paul M. , McArthur David , O'Phelan Kristine , Glenn Thomas , Etchepare Maria , Kelly Daniel , Bergsneider Marvin , Martin Neil A. , Hovda David A.
Published: November 2003

Disturbed glucose brain metabolism after brain trauma is reflected by changes in extracellular glucose levels. The authors hypothesized that posttraumatic reductions in extracellular glucose levels are not due to ischemia and are associated with poor outcome. Intracerebral microdialysis, electroencephalography, and measurements of brain tissue oxygen levels and jugular venous oxygen saturation were performed in 30 patients with traumatic brain injury. Levels of glucose, lactate, pyruvate, glutamate, and urea were analyzed hourly. The 6-month Glasgow Outcome Scale extended (GOSe6) score was assessed for each patient. In regions of increased glucose utilization defined by positron emission tomography, the extracellular glucose concentration was less than 0.2 mmol/l. Extracellular glucose values were less than 0.2 mmol during postinjury days 0 to 7 in 19% to 30% of hourly samples on each day. Transient decreases in glucose levels occurred with electrographic seizures and nonischemic reductions in cerebral perfusion pressure and jugular venous oxygen saturation. Glutamate levels were elevated in the majority of low-glucose samples, but the lactate/pyruvate ratio did not indicate focal ischemia. Terminal herniation resulted in reductions in glucose with increases in the lactate/pyruvate ratio but not in lactate concentration alone. GOSe6 scores correlated with persistently low glucose levels, combined early low glucose levels and low lactate/glucose ratio, and with the overall lactate/glucose ratio. These results suggest that the level of extracellular glucose is typically reduced after traumatic brain injury and associated with poor outcome, but is not associated with ischemia.
L-Arginine Levels in Blood as a Marker of Nitric Oxide–Mediated Brain Damage in Acute Stroke: A Clinical and Experimental Study
Authors: Armengou Arola , Hurtado Olivia , Leira Rogelio , Obón María , Pascual Carlos , Moro María A , Lizasoain Ignacio , Castillo José , Dávalos Antoni
Published: November 2003

There are no useful markers in blood of nitric oxide (NO)-mediated brain damage. Because l-arginine (l-arg) is the only known substrate for NO generation, the authors investigated the plasma profile of l-arg after cerebral ischemia, and the relationship of L-arg concentrations in blood with stroke outcome and infarct volume in a clinical and experimental study. l-Arg levels were determined with high-performance liquid chromatography in blood and CSF samples obtained on admission, and in blood 48 hours after inclusion, in 268 patients admitted with a hemispheric ischemic stroke lasting 8.2 ± 5.9 hours. Infarct volume was measured by days 4 to 7 using computed tomography. Plasma l-arg profiles were analyzed in a separate group of 29 patients seen within 8 hours of onset (median, 4.5 hours) and in 24 male Fischer rats treated with subcutaneous vehicle or 20-mg/kg 1400W (a specific inducible NO synthase inhibitor) every 8 hours for 3 days after performing sham or permanent middle cerebral artery occlusion. Plasma l-arg concentrations decreased after the ischemic event, both in patients and rats, and peaked between 6 and 24 hours. In patients, there was a highly correlation between l-arg levels in CSF and plasma at 48 hours ( r = 0.85, P< 0.001). CSF and plasma l-arg concentrations negatively correlated with infarct volume ( r = −0.40 and r = −0.35, respectively, P <0.001), and were significantly lower in patients with early neurologic deterioration and in those with poor outcome (Barthel index <85) at 90 days ( P <0.001). In rats, the administration of 1400W resulted in a 55% significant reduction of infarct volume measured 72 hours after permanent middle cerebral artery occlusion, an effect that correlated with the inhibition caused by 1400W on the ischemia-induced decrease of plasma l-arg concentrations at 6 to 24 hours after the onset of the ischemia. Taken together, these data indicate that determination of l-arg levels in blood might be useful to evaluate the neurotoxic effects of NO generation. These findings might be helpful to guide future neuroprotective strategies in patients with ischemic stroke.
Biphasic Changes in Tissue Partial Pressure of Oxygen Closely Related to Localized Neural Activity in Guinea Pig Auditory Cortex
Authors: Masamoto Kazuto , Omura Tetsuro , Takizawa Naosada , Kobayashi Hirosuke , Katura Takusige , Maki Atsushi , Kawaguchi Hideo , Tanishita Kazuo
Published: November 2003

An understanding of the local changes in cerebral oxygen content accompanying functional brain activation is critical for making a valid signal interpretation of hemodynamic-based functional brain imaging. However, spatiotemporal relations between changes in tissue partial pressure of oxygen (Po2) and induced neural activity remain incompletely understood. To characterize the local Po2 response to the given neural activity, the authors simultaneously measured tissue Po2 and neural activity in the identical region of guinea pig auditory cortex with an oxygen microelectrode (tip < 10 μm) and optical recording with voltage-sensitive dye (RH 795). In addition, a laser displacement gauge and a laser-Doppler flowmeter were used to monitor the spatial displacement and regional cerebral blood flow, respectively, in the Po2 measurement region. In the activated region, tissue Po2 initially decreased during the ∼3seconds after the onset of acoustic stimuli, and then increased during the next ∼5 seconds. Such biphasic changes are consistently found in cortical layers I to IV. In addition, amplitude of the biphasic change was closely related to detected peak height of the optical signal changes. The results suggest that the initial decrease in tissue Po2 is coupled to the induced neural activity and depends on response time of local increase in cerebral blood flow.
Central Nervous System–Targeted Complement Inhibition Mediates Neuroprotection after Closed Head Injury in Transgenic Mice
Authors: Rancan Mario , Morganti-Kossmann Maria C. , Barnum Scott R. , Saft Silvia , Schmidt Oliver I. , Ertel Wolfgang , Stahel Philip F.
Published: November 2003

The role of intracerebral complement activation after traumatic brain injury remains unclear. In this study, the authors demonstrate that transgenic mice with astrocyte-targeted expression of the soluble complement inhibitor sCrry have a significantly reduced neurologic impairment and improved blood–brain barrier function after closed head injury compared with wild-type C57BL/6 littermates. This work further implicates the complement system as a participant in secondary progression of brain damage after head trauma and provides a strong rationale for future studies of posttraumatic pharmacologic complement inhibition.
Neuroprotective Effects of Insulin-Like Growth Factor-Binding Protein Ligand Inhibitors in Vitro and in Vivo
Authors: Mackay Kenneth B , Loddick Sarah A , Naeve Gregory S , Vana Alicia M , Verge Gail M , Foster Alan C
Published: November 2003

The role of brain insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in neuroprotection was further investigated using in vitro and in vivo models of cerebral ischemia by assessing the effects of IGF-I, IGF-II, and high affinity IGFBP ligand inhibitors (the peptide [Leu24, 59, 60, Ala31]hIGF-I (IGFBP-LI) and the small molecule NBI-31772 (1-(3,4-dihydroxybenzoyl)-3-hydroxycarbonyl-6, 7-dihydroxyisoquinoline), which pharmacologically displace and elevate endogenous, bioactive IGFs from IGFBPs. Treatment with IGF-I, IGF-II, or IGFBP-LI (2 μg/mL) significantly ( P < 0.05) reduced CA1 damage in organotypic hippocampal cultures resulting from 35 minutes of oxygen and glucose deprivation by 71%, 60%, and 40%, respectively. In the subtemporal middle cerebral artery occlusion (MCAO) model of focal ischemia, intracerebroventricular (icv) administration of IGF-I and IGF-II at the time of artery occlusion reduced ischemic brain damage in a dose-dependent manner, with maximum reductions in total infarct size of 37% ( P < 0.01) and 38% ( P < 0.01), respectively. In this model of MCAO, icv administration of NBI-31772 at the time of ischemia onset also dose-dependently reduced infarct size, and the highest dose (100 μg) significantly reduced both total (by 40%, P < 0.01) and cortical (by 43%, P < 0.05) infarct volume. In the intraluminal suture MCAO model, administration of NBI-31772 (50 μg icv) at the time of artery occlusion reduced both cortical infarct volume (by 40%, P < 0.01) and brain swelling (by 24%, P < 0.05), and it was still effective when treatment was delayed up to 3 hours after the induction of ischemia. These results further define the neuroprotective properties of IGFs and IGFBP ligand inhibitors in experimental models of cerebral ischemia.
Overexpression of HDJ-2 Protects Astrocytes from Ischemia-Like Injury and Reduces Redistribution of Ubiquitin Staining in Vitro
Authors: Qiao Yanli , Ouyang Yi-Bing , Giffard Rona G
Published: November 2003

HDJ-2, a member of the HSP40 family, functions as a cochaperone to promote protein folding both by binding to unfolded polypeptides and by regulating the activity of HSP70. This study tested whether HDJ-2 overexpression alone could provide significant protection from ischemia-like injury. Primary mouse astrocyte cultures were infected with an HDJ-2 encoding retroviral vector or control retrovirus lacking HDJ-2. Expression of HDJ-2 was confirmed by immunohistochemical staining and immunoblotting. Injury paradigms to mimic ischemia were glucose deprivation (GD) for 24 hours and oxygen-glucose deprivation (OGD) for 8 hours. Cell death was determined by trypan blue exclusion and cell counting. Overexpression of HDJ-2 alone significantly reduced astrocyte injury after both GD and OGD, independent of an elevation in HSP70. To further search for the mechanism of HDJ-2 protection, cultured astrocytes allowed to recover 16 hours after 8 hours GD were labeled with a monoclonal antiubiquitin antibody that recognizes both free ubiquitin and ubiquitinated proteins. The immunolabeling pattern changed from a relatively even distribution in both nuclei and cytoplasm in control cells to heterogeneous aggregates and marked reduction of nuclear staining in most of the cells after GD. When HDJ-2 was overexpressed, the number of cells with evidence of protein aggregation was significantly reduced. Thus, blocking protein aggregation may be an important mechanism by which HDJ-2 protects cells from damage.
Energy Dysfunction as a Predictor of Outcome after Moderate or Severe Head Injury: Indices of Oxygen, Glucose, and Lactate Metabolism
Authors: Glenn Thomas C , Kelly Daniel F , Boscardin W John , McArthur David L , Vespa Paul , Oertel Matthias , Hovda David A , Bergsneider Marvin , Hillered Lars , Martin Neil A
Published: November 2003

The purpose of this study was to determine if the relationship between abnormalities in glucose, lactate, and oxygen metabolism were predictive of neurologic outcome after moderate or severe head injury, relative to other known prognostic factors. Serial assessments of the cerebral metabolic rates for glucose, lactate, and oxygen were performed using a modified Kety-Schmidt method. In total, 31 normal control subjects were studied once, and 49 TBI patients (mean age 36±16 years, median GCS 7) were studied five times median per patient from postinjury days 0 to 9. Univariate and multivariate analyses were performed. Univariate analysis showed that the 6-month postinjury Glasgow Outcome Scale (GOS) was most strongly associated with the mean cerebral metabolic rate of oxygen (CMRO2) ( P = 0.0001), mean arterial lactate level ( P = 0.0001), mean arterial glucose ( P = 0.0008), mean cerebral blood flow (CBF), ( P = 0.002), postresuscitation GCS ( P = 0.003), and pupillary status ( P = 0.004). Brain lactate uptake was observed in 44% of all metabolic studies, and 76% of patients had at least one episode of brain lactate uptake. By dichotomized GOS, patients achieving a favorable outcome (GOS 4-5) were distinguished from those with an unfavorable outcome (GOS1-3) by having a higher CMRO2 ( P = 0.003), a higher rate of abnormal brain lactate uptake relative to arterial lactate levels ( P = 0.04), and lesser degrees of blood-brain barrier damage based on CT findings ( P = 0.03). Conclusions: During the first 6 days after moderate or severe TBI, CMRO2 and arterial lactate levels are the strongest predictors of neurologic outcome. However, the frequent occurrence of abnormal brain lactate uptake despite only moderate elevations in arterial lactate levels in the favorable outcome patients suggests the brain's ability to use lactate as a fuel may be another key outcome predictor. Future studies are needed to determine to what degree nonglycolytic energy production from alternative fuels such as lactate occurs after TBI and whether alternative fuel administration is a viable therapy for TBI patients.
Transforming Growth Factor-β1-Mediated Neuroprotection against Excitotoxic Injury in Vivo
Authors: Boche Delphine , Cunningham Colm , Gauldie Jack , Perry V Hugh
Published: November 2003

Ischemic preconditioning is a phenomenon that describes how a sublethal ischemic insult can induce tolerance to subsequent ischemia. This phenomenon has been observed after focal or global ischemia in different animal models. However, the hypothesis that bacterial infection might lead to neuronal tolerance to injury has not been investigated. To mimic cerebral bacterial infection, we injected bacterial lipopolysaccharide (LPS) in the right dorsal hippocampus, followed 24 hours later by an excitotoxic lesion using kainic acid in the mouse model. Quantification of lesion size after cresyl violet counterstaining revealed that LPS pretreatment afforded neuroprotection to CA3 neurons against KA challenge. To investigate the events underlying this protection, we studied the cytokine profile induced after LPS injection. Interleukin (IL)-1β and transforming growth factor beta 1 (TGF-β1) were the main cytokines expressed at 24 hours after LPS injection. Because IL-1β has been described as deleterious in acute injury, we decided to investigate the function of TGF-β1. An adenovirus expressing a constitutively active form of TGF-β1 was injected intracerebrally 1 week before the induction of excitotoxic lesion, and neuronal protection was observed. To confirm the neuroprotective role of TGF-β1, the TGF-β1 adenovirus was replaced by recombinant human TGF-β1 protein and total neuroprotection was observed. Furthermore, the antibody-mediated blocking of TGF-β1 action prevented the protective effect of pretreatment with LPS. We have demonstrated in vivo that the cerebral tolerance phenomenon induced by LPS pretreatment is mediated by TGF-β1 cytokine.
Responses of Posttraumatic Pericontusional Cerebral Blood Flow and Blood Volume to an Increase in Cerebral Perfusion Pressure
Authors: Steiner Luzius A , Coles Jonathan P , Johnston Andrew J , Czosnyka Marek , Fryer Tim D , Smielewski Peter , Chatfield Doris A , Salvador Raymond , Aigbirhio Franklin I , Clark John C , Menon David K , Pickard John D
Published: November 2003

In and around traumatic contusions, cerebral blood flow (CBF) is often near or below the threshold for ischemia. Increasing cerebral perfusion pressure (CPP) in patients with head injuries may improve CBF in these regions. However, the pericontusional response to this intervention has not been studied. Using positron emission tomography (PET), we have quantified the response to an increase in CPP in and around contusions in 18 contusions in 18 patients. Regional CBF and cerebral blood volume (CBV) were measured with PET at CPPs of 70 and 90 mmHg using norepinephrine to control CPP. Based upon computed tomography, regions of interest (ROIs) were placed as two concentric ellipsoids, each of 1-cm width, around the core of the contusions. Measurements were compared with a control ROI in tissue with normal anatomic appearance. Baseline CBF and CBV increased significantly with increasing distance from the core of the lesion. The increase in CPP led to small increases in CBF in all ROIs except the core. The largest absolute CBF increase was found in the control ROI. Relative CBF increases did not differ between ROIs so that ischemic areas remained ischemic. Pericontusional oedema on computed tomography was associated with lower absolute values of CBF and CBV but did not differ from nonoedematous tissue in the relative response to CPP elevation.
Cerebral and Cerebellar Activation in Power and Precision Grip Movements: An H215O Positron Emission Tomography Study
Authors: Takasawa Masashi , Oku Naohiko , Osaki Yasuhiro , Kinoshita Hiroshi , Imaizumi Masao , Yoshikawa Takuya , Kimura Yasuyuki , Kajimoto Katsufumi , Sasagaki Michihiro , Kitagawa Kazuo , Hori Masatsugu , Hatazawa Jun
Published: November 2003

Most human manual grip movements can be divided into power gripping and precision gripping, but central neural control during these tasks remains unclear. We investigated activation of the whole brain to analyze how simple hand movements are performed. The cerebral blood flow of seven healthy right-handed volunteers was measured by H215O positron emission tomography during right grip tasks without gripping a target object. Auditory-cued, repetitive power grips (i.e., fist making) and repetitive precision grips (i.e., opposition of the tip of the index finger and the tip of the thumb) were performed at 1.26 Hz. The areas activated during both tasks were the left primary sensorimotor cortex, caudal portion of the dorsal premotor, caudal portion of the supplementary motor area, cingulate motor area, and the right spinocerebellum and intermediate region of the cerebrocerebellum in comparison with the rest state. The analysis of power grip-precision grip tasks showed the activated peaks in the upper portion of the left sensorimotor area and right cerebellar vermis, but these areas were activated in both the tasks [(power grip-rest) and (precision grip-rest)] with uncorrected P < 0.001 as the statistical criterion. With P < 0.05 corrected as the statistical criterion, the results showed no significant activated peaks in regional cerebral blood flow. Our findings indicate no difference in brain activation between the acts of power grip and precision grip without a target object.
Inducible Repair of Oxidative DNA Lesions in the Rat Brain after Transient Focal Ischemia and Reperfusion
Authors: Lan Jing , Li Wenjin , Zhang Feng , Sun Feng-Yan , Nagayama Tetsuya , O'Horo Cristine , Chen Jun
Published: November 2003

To determine the role of oxidative DNA damage and repair in brain injury after focal ischemia and reperfusion, the authors investigated DNA base damage and DNA base excision repair (BER) capacity, the predominant repair mechanism for oxidative DNA lesions, in the rat model of temporary middle cerebral artery occlusion. Contents of 8-hydroxyl-2′-deoxyguanosine (8-oxodG) and apurinic/apyrimidinic abasic site (AP site), hallmarks of oxidative DNA damage, were quantitatively measured in nuclear DNA extracts from brains 0.25 to 72 hours after 1 hour of middle cerebral artery occlusion. In parallel to the detection of DNA lesions, the capacity for 8-oxodG- or AP site-dependent DNA repair synthesis was measured in nuclear protein extracts using specific in vitro DNA repair assays. After postischemic reperfusion, the levels of 8-oxodG and AP sites were markedly increased in ischemic tissues. In frontal/parietal cortex, regions that survived ischemia, 8-oxodG and AP sites were efficiently repaired during reperfusion. However, in the caudate, a region that was destined to infarct, the DNA lesions were poorly repaired. In consistent with the patterns of endogenous lesion repair, a markedly induced and long-lasting (at least 72 hours) BER activity was detected in the cortex but not in the caudate after ischemia. The induced BER activity in ischemic cortex was attributed to the upregulation of gene expression and activation of selective BER enzymes, particularly DNA polymerase-β and OGG1. These results strongly suggest that inducible DNA BER constitutes an important endogenous mechanism that protects brain against ischemia-induced oxidative neuronal injury.
The Protective Effects of Preconditioning on Cerebral Endothelial Cells in Vitro
Authors: Andjelkovic Anuska V , Stamatovic Svetlana M , Keep Richard F
Published: November 2003

Ischemic preconditioning (PC) can markedly reduce ensuing ischemic damage. Although most attention has focused on the neuronal effects of PC, the authors have recently shown that ischemic PC reduces ischemia-induced cerebrovascular damage. In vivo, it is difficult to ascertain whether this is a direct cerebrovascular effect of PC. This study, therefore, examined whether cerebral endothelial cells can be preconditioned in vitro in the absence of other cell types. Experiments were performed on an immortalized mouse brain endothelial cell line or primary cultures of mouse brain microvessel endothelial cells. Cells were exposed to oxygen glucose deprivation (OGD) of either short duration, as a PC stimulus, or a long duration (5 hours) with or without reoxygenation to induce endothelial damage. Endothelial injury was assessed by measuring lactate dehydrogenase release and the expression of intercellular adhesion molecule-1 at the protein and mRNA levels. Experiments indicated that 1 hour of OGD was the optimal PC stimuli and that a 1 or 3 day interval was the optimal time interval between the PC stimulus and the injurious event. Preconditioned cells had less lactate dehydrogenase release during OGD (± reoxygenation) and reduced intercellular adhesion molecule-1 expression after OGD with reoxygenation. This study shows that cerebral endothelial cells can be directly preconditioned. The importance of this phenomenon in the overall effects of PC on the brain remains to be elucidated. Understanding the protective mechanisms elicited by PC may give insight into how to prevent ischemia-induced vascular damage (e.g., hemorrhagic transformation).
Axon Function Persists during Anoxia in Mammalian White Matter
Authors: Tekkök Selva Baltan , Brown Angus M , Ransom Bruce R
Published: November 2003

Axon function in the CNS has been reported to fail rapidly during anoxia, implying that there is no anaerobic capacity. This phenomenon was reassessed in rodent white matter using mouse or rat optic nerve. Axon function was semiquantitatively measured as area under the compound action potential. Mouse optic nerves exposed to anoxia (30–180 minutes) or cyanide (30–60 minutes) at 37°C exhibited significant persistent function that was abolished by removing glucose. Reduction in compound action potential area increased with anoxia duration reaching a maximum of about 70% after 90 min. Rat optic nerves exposed to anoxia, in contrast to mouse optic nerves, showed rapid and complete loss of function. When artificial CSF glucose was increased from 10 to 30 mmol/L, rat optic nerves responded to anoxia in a similar manner to mouse optic nerves in 10-mmol/L glucose. The authors conclude that white matter is resistant to anoxia with a subset of axons able to subsist exclusively on anaerobically derived energy. Because the rat optic nerve is about twice the diameter of the mouse optic nerve, glucose diffusion into the rat optic nerve was inadequate during anoxia when artificial CSF glucose was 10 mmol/L but became adequate when artificial CSF glucose was 30 mmol/L. These observations have implications for white matter energy metabolism and susceptibility to injury during focal ischemia.
Hypointense Transcerebral Veins at T2∗-Weighted MRI: A Marker of Hemorrhagic Transformation Risk in Patients Treated with Intravenous Tissue Plasminogen Activator
Authors: Hermier Marc , Nighoghossian Norbert , Derex Laurent , Adeleine Patrice , Wiart Marlène , Berthezène Yves , Cotton François , Pialat Jean-Baptiste , Dardel Pascal , Honnorat Jérôme , Trouillas Paul , Froment Jean-Claude
Published: November 2003

Prediction of hemorrhagic transformation (HT) in patients treated by intravenous recombinant tissue-type plasminogen activator (rt-PA) is a challenging issue in acute stroke management. HT may be correlated with severe hypoperfusion. Signal changes may be observed at susceptibility-weighted magnetic resonance imaging (MRI) within large perfusion defects. A signal drop within cerebral veins at T2∗-weighted gradient-echo MRI may be expected in severe ischemia, and may indicate subsequent risk of HT. The authors prospectively searched for an abnormal visibility of transcerebral veins (AVV) within the ischemic area in patients with hemispheric ischemic stroke, before they were treated with intravenous rt-PA therapy. Any correlation between AVV and baseline clinical or MRI findings, or further HT, was noted. An AVV was present in 23 of 49 patients (obvious, n = 8; moderate, n = 15), and was supported by severe hemodynamic changes at baseline MRI. The AVV was correlated with the occurrence of parenchymal hematoma type 2 at computed tomography during the first week ( r = 0.44, P = 0.002). Five of six type 2 parenchymal hematomas occurred in association with obvious AVV. At multiple regression analysis, two baseline MRI factors had an independent predictive value for HT risk during the first week: the AVV and the cerebral blood volume ratio (Nagelkerke R2 = 0.48).
A Conserved Pore‐Lining Glutamate as a Voltage‐ and Chloride‐Dependent Gate in the ClC‐2 Chloride Channel
Authors: Niemeyer María Isabel , Cid L. Pablo , Zúñiga Leandro , Catalán Marcelo , Sepúlveda Francisco V.
Published: November 2003

ClC‐2 is a ubiquitously expressed, two‐pore homodimeric Cl− channel opened by hyperpolarisation. Little is known about its gating mechanisms. Crystallographic and functional studies in other ClC channels suggest that a conserved glutamate residue carboxylate side‐chain can close protopores by interacting with a Cl−‐binding site in the pore. Competition for this site is thought to provide the molecular basis for gating by extracellular Cl−. We now show that ClC‐2 gating depends upon intra‐ but not extracellular Cl− and that neutralisation of E217, the homologous pore glutamate, leads to loss of sensitivity to intracellular Cl− and voltage. Experiments testing for transient activation by extracellular protons demonstrate that E217 is not available for protonation in the closed channel state but becomes so after opening by hyperpolarisation. The results suggest that E217 is a hyperpolarisation‐dependent protopore gate in ClC‐2 and that access of intracellular Cl− to a site normally occupied by its side‐chain in the pore stabilises the open state. A remaining hyperpolarisation‐dependent gate might correspond to that closing both pores simultaneously in other ClC channels.
Isocyanide insertion reactions into the TaC bonds of cationic and zwitterionic tantalocenes
Authors: Cook Kevin S , Piers Warren E , Patrick Brian O , McDonald Robert
Published: November 2003

The insertion of isonitriles R' NC (R' = t-Bu, C6H11, CH2C6H5) occurs exclusively into the TaCH2 bonds of the zwitterionic compounds (C5H4R)2Ta[CH2B(C6F5)3]CH3 (R = H, 1a; R = CH3, 1b) at relatively slow rates at room temperature to form N-out isomers as the sole kinetic products. By comparison, insertion of the same isonitrile substrates into a TaCH3 bond of the non-zwitterionic analogs [(C5H4R)2Ta(CH3)2][A] (R = H, A = B(C6F5)4, 3a; R = CH3, A = BF4, 3b) occurs much more rapidly, again to form N-out isomers exclusively under kinetic conditions. The difference in rate is attributed to the presence of a ground state α-agostic interaction in the zwitterionic compounds, which is not featured in the dimethyl ion pairs. All of the N-out isomers formed undergo thermal and irreversible conversion to the corresponding N-in isomers at rates that are conveniently followed by 1H NMR spectroscopy. The rates were studied at different temperatures to obtain activation parameters for each transformation. The rate and activation trends for this isomerization were analyzed as a function of the structural changes in the compounds. It was found that the rate decreased as the steric bulk of the isonitrile substitutent R' increased and that the rates were faster for the series that incorporated the more electron-donating C5H4CH3 ancillary ligand. Furthermore, isomerization rates for the zwitterionic N-out compounds were faster than those found in the non-zwitterionic series. This study represents one of the more extensive kinetic analyses of the rate of N-out to N-in isomerization as a function of structural changes. The observations are consistent with the mechanistic picture that has been developed for this process, involving dissociation of the η2 iminoacyl ligand, rotation about the MCiminoacyl bond and recoordination to the inside site of the metallocene wedge. Key words: cationic metallocenes, isocyanide insertion, agostic interactions, tantalum.
Molecular modelling of self-assembled alkynyl monolayer structures  Unnatural symmetry units, surface bonding, and topochemical polymerization1
Authors: Dickie Adam J , Kakkar Ashok K , Whitehead Michael A
Published: November 2003

Geometric modelling techniques are used to map the potential energies of packing for self-assembled alkyl- and phenyl-backboned monolayers across a range of intermolecular separations. Natural packing distances of 4.24.4 Å produce less stable, more isotropic monolayers because of repulsive interchain contacts. Optimizations at unnatural surface densities found thin films of lower energy and higher symmetry existed at increased chainchain separations. Head-group bonding is therefore identified as a force for controlling monolayer order. Analysis of the natural monolayer structures on a silicon dioxide surface determined the favourable head-group structures, and allowed the topochemical polymerization of p-bis(butadiynyl)benzene monolayers to be rationalized.Key words: self-assembled monolayers, molecular modelling studies, repeating symmetry units, thin-film order, topochemical polymerization.
Synthesis, characterization, and polycondensation of new stable α,ω-organo(bis-silanediols)
Authors: Cerveau Geneviève , Chappellet Sabrina , Corriu Robert JP , Dabiens Bertrand
Published: November 2003

The synthesis and characterization of stable bis(dihydroxymethylsilyl) derivatives are described. These compounds were obtained as microcrystalline powders by controlled hydrolysis in a biphasic medium (ethyl ether  water) of the corresponding bis(dimethoxymethylsilyl) organic precursors containing phenyl, biphenyl, stilbenyl, diphenyl acetylene, and diphenylbut-1,3-diyne groups. All the solids obtained exhibited a layered structure. Condensation of the bis-silanediols could be effected by fluoride catalysis in solution at ambient temperature or simply by heating in solid state. The polysiloxanes obtained from the bis-silanediols have been compared with those obtained by hydrolysispolycondensation of the corresponding bis-dimethoxysilanes. The thermal route led to highly polycondensed solids arranged into thin plates as evidenced by TEM analysis; furthermore, in the case of the longer spacer, the organization was controlled by the arrangement of the Si-O-Si layers instead of the spacer. The X-ray study of these materials clearly evidenced the drastic influence of the length of the organic spacer, the polycondensation route and the nature of the leaving group (hydroxy or methoxy) on the short-range organization of the solids. Key words: silanols, hybrid materials, polycondensation, polysiloxanes.
The mechanism of protonolysis of phenylplatinum(II) bonds in complexes with phenyl trans to nitrogen or carbon donors
Authors: Ong Christopher M , Jennings Michael C , Puddephatt Richard J
Published: November 2003

Addition of acids of the form HX (X = Cl, BF4, CF3SO3, CF3CO2) to complexes [PtPh2(NN)] (NN = bu2bpy = 4,4'-di-tert-butyl-2,2'-bipyridine) and [PtPh(NCN)] (NCN = 2,6-C6H3(CH2NMe2)2) at 78 °C gave the corresponding phenyl(hydrido)platinum(IV) complexes [PtX(H)Ph2(NN)] and [PtX(H)Ph(NCN)], which decomposed by reductive elimination of benzene at about 20 °C to give the platinum(II) complexes [PtXPh(NN)] and [PtX(NCN)]. Further addition of HCl to [PtClPh(NN)] at low temperature gave [PtHCl2Ph(NN)], which decomposed above 10 °C, to give benzene and [PtCl2(NN)]. The reaction of DBF4 in the presence of excess CD3OD with [PtPh2(NN)] led to formation of C6H5D and C6H4D2 but with [PtPh(NCN)] no multiple deuterium incorporation was observed in the product benzene. The mechanisms of these reactions are discussed. Key words: platinum, phenyl, benzene, protonolysis.
A metal-free catalytic intramolecular hydrosilylation
Authors: Steinberger Hans-Uwe , Bauch Christian , Müller Thomas , Auner Norbert
Published: November 2003

A metal-free catalytic intramolecular hydrosilylation reaction is reported. The key intermediates in the catalytic cycle are silyl cationic species. The reaction is used to produce 2-silanorbornanes 2 from 3-cyclopentenemethylsilanes 1 under mild conditions and in high isolated yields.Key words: hydrosilylation, catalysis, silaheterocycles, silyl cations.
Synthesis, structure, and reactivity of hydridobis(silylene)ruthenium(IV)-xantsil complexes (xantsil = (9,9-dimethylxanthene-4,5-diyl)bis(dimethylsilyl)) — A stabilized form of key intermediates in the catalytic oligomerization–deoligomerization of hydrosilanes
Authors: Okazaki Masaaki , Gabrillo Minglana Jim Josephus , Yamahira Nobukazu , Tobita Hiromi , Ogino Hiroshi
Published: November 2003

Ru{κ2(Si,Si)-xantsil}(CO)(η6-C6H5CH3) (1) was found to be a catalyst for oligomerization–deoligomerization of HSiMe2SiMe3 to give H(SiMe2)nMe (n = 1–8 at 90 °C for 2 days). Treatment of 1 with HSiMe2SiMe2OR (R = Me, t-Bu) led to quantitative formation of Ru{κ3(O,Si,Si)-xantsil}(CO)(H){(SiMe2O(R)SiMe2)} (R = Me (2a), t-Bu (2b)), which also worked as a catalyst for oligomerization–deoligomerization of HSiMe2SiMe3. Based on these experimental results, a mechanism involving silyl(silylene) intermediates was proposed for the oligomerization–deoligomerization of HSiMe2SiMe3. Complex 2a reacted with MeOH in toluene-d8 to give Ru{κ2(Si,Si)-xantsil}(CO)(η6-toluene-d8) and Me2Si(OMe)2 with evolution of H2. Under a CO atmosphere, 2a was smoothly converted to its CO adduct Ru{κ2(Si,Si)-xantsil}(CO)2(H){(SiMe2O(Me)SiMe2)} (3).Key words: silylene complex, ruthenium, polysilane, dehydrogenative coupling, oligomerization.
Lewis acidity of group 14 elements toward intramolecular sulfur in ortho-aryl-thioanisoles
Authors: Munguia Teresita , Pavel Ioana S , Kapoor Ramesh N , Cervantes-Lee Francisco , Párkányi László , Pannell Keith H
Published: November 2003

The series of compounds (o-CH3SC6H4)CH2EPh3(E = Si (1), Ge (2), Sn (3), and Pb (4)) have been synthesized and characterized by NMR spectroscopy and by single crystal X-ray diffraction. Compounds 1 and 2 are isostructural with a triclinic crystal system and P-1 space group; however, morphotropic steps occur between Ge and Sn, and Sn and Pb. While the E-S distances in 1 and 2 are 3.985 and 3.974 Å, respectively, ~100% of the sum of the respective van der Waals (vdW) radii, there is a notable distortion from tetrahedral geometry about E. Compound 3 is also triclinic with P-1 symmetry, but has two molecules in the unit cell that demonstrate a distorted tetrahedral geometry and intramolecular Sn-S distances of 3.699 and 3.829 Å, 88% and 91% of the sum of the vdW radii. Compound 4 has a Pb-S distance of 3.953 Å (91% of Σ vdW radii). The structure of the Grignard coupling product [o-(SCH3)C6H4CH2]2is also reported.Key words: intramolecular self-assembly, silicon, germanium, tin, lead, sulfur.
Shear Stress Increases ICAM-1 and Decreases VCAM-1 and E-selectin Expressions Induced by Tumor Necrosis Factor-α in Endothelial Cells
Authors: Chiu Jeng-Jiann , Lee Pei-Ling , Chen Cheng-Nan , Lee Chih-I , Chang Shun-Fu , Chen Li-Jing , Lien Sheng-Chieh , Ko Ya-Chen , Usami Shunichi , Chien Shu
Published: November 2003

Objective—Vascular endothelial cells (ECs) are subjected to shear stress and cytokine stimulation. We studied the interplay between shear stress and cytokine in modulating the expression of adhesion molecule genes in ECs.

Methods and Results—Shear stress (20 dynes/cm2) was applied to ECs prior to and/or following the addition of tumor necrosis factor (TNF)-α. Shear stress increased the TNF-α–induced expression of intercellular adhesion molecule-1 (ICAM-1) at both mRNA and surface protein levels, but decreased the TNF-α–induced expression of vascular adhesion molecule-1 (VCAM-1) and E-selectin. Transfection studies using promoter reporter gene constructs of ICAM-1, VCAM-1, and E-selectin demonstrated that these shear stress modulations of gene expression occur at the transcriptional levels. After 24-hour preshearing followed by 1 hour of static incubation, the effect of preshearing on TNF-α–induced ICAM-1 mRNA expression vanished. The recovery of the TNF-α–induced VCAM-1 and E-selectin mRNA expressions following preshearing, however, required a static incubation time of >6 hours (complete recovery at 24 hours). Pre- and postshearing caused a reduction in the nuclear factor-κB-DNA binding activity induced by TNF-α in the EC nucleus.

Conclusions—Our findings suggest that shear stress plays differential roles in modulating the TNF-α–induced expressions of ICAM-1 versus VCAM-1 and E-selectin genes in ECs.