bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dexmedetomidine Increases Hippocampal Phosphorylated Extracellular Signal–regulated Protein Kinase 1 and 2 Content by an α2-Adrenoceptor–independent Mechanism
Authors: Dahmani Souhayl , Paris Andrea , Jannier Virginie , Hein Lutz , Rouelle Danielle , Scholz Jens , Gressens Pierre , Mantz Jean 
Published: March 2009

Background
Dexmedetomidine is a potent and selective alpha2-adrenoceptor (alpha2AR) agonist that exhibits a broad pattern of actions, including sedation, analgesia, and neuroprotection. Recent studies have emphasized the role of phosphorylated extracellular signal-regulated protein kinases (pERK1 and 2) in coupling rapid events such as neurotransmitter release and receptor stimulation long-lasting changes in synaptic plasticity and cell survival. Here, the authors hypothesized that dexmedetomidine increases pERK1 and 2 content and examined the mechanisms involved in this effect.

Methods
The effects of dexmedetomidine and their sensitivity to various pharmacologic agents on expression of pERK1 and 2 were studied by Western blots in hippocampal slices obtained from rats, wild-type mice, and mice carrying targeted deletions of the alpha2AR subtypes.

Results
Dexmedetomidine induced a concentration-related increase in the expression of pERK1 and 2 in rat hippocampal slices (EC50 [95% confidence interval] for pERK1, 0.97 [0.68-1.37] microm; for pERK2, 1.15 [0.62-2.14] microm). This effect was insensitive to the inhibitors of the alpha2AR-mediated signaling pathway, to prazosin, and to PP2, an inhibitor of the focal adhesion kinase-Src kinases. In contrast, it was still present in mice deleted for each of the alpha2AR subtypes and was markedly decreased by the antagonist of the I1-imidazoline receptors efaroxan, by phospholipase C and protein kinase C inhibitors, and by PD 098059, a direct inhibitor of ERK1 and 2 phosphorylation.

Conclusion
Dexmedetomidine increases the expression of pERK1 and 2 via mechanisms independent of alpha2AR activation. The I1-imidazoline receptors likely contribute to these effects. The results may be relevant to some long-term effects (e.g., neuroprotective) of dexmedetomidine in the brain.
Gabapentin Prevents Delayed and Long-lasting Hyperalgesia Induced by Fentanyl in Rats
Authors: Van Elstraete Alain C. , Sitbon Philippe , Mazoit Jean-Xavier , Benhamou Dan 
Published: March 2009

Background
Opioid-induced hyperalgesia can develop rapidly after opioid exposure. Neuropathic pain and opioid-induced hyperalgesia share common pathophysiologic mechanisms. Gabapentin is effective for the management of neuropathic pain and may therefore prevent opioid-induced hyperalgesia. This study tested the effectiveness of gabapentin for prevention of long-lasting hyperalgesia induced by acute systemic fentanyl in uninjured rats. Involvement of the alpha2delta auxiliary subunits of voltage-gated calcium channels in the prevention of opioid-induced hyperalgesia by gabapentin also was assessed.

Methods
Hyperalgesia was induced in male Sprague-Dawley rats with subcutaneous fentanyl (four injections, 20, 60, or 100 microg/kg per injection at 15-min intervals). Intraperitoneal (30, 75, 150, or 300 mg/kg) or intrathecal (300 microg) gabapentin was administered 30 min before or 300 min after (intraperitoneal 150 mg/kg) the first fentanyl injection. Sensitivity to nociceptive stimuli (paw-pressure test) was assessed on the day of the experiment and for several days after injections. The effects combining gabapentin with intrathecal ruthenium red (20 ng) also were assessed.

Results
Fentanyl administration was followed by an early increase (analgesia) and by a later and sustained decrease (hyperalgesia) in nociceptive thresholds. Gabapentin did not significantly modify the early analgesic component but dose-dependently prevented the delayed decrease in nociceptive threshold. Ruthenium red partially, but significantly, opposed the prevention of opioid-induced hyperalgesia by gabapentin.

Conclusions
Intraperitoneal and intrathecal gabapentin prevents the development of hyperalgesia induced by acute systemic exposure to opioids. This prevention may result, at least in part, from binding of gabapentin to the alpha2delta auxiliary subunits of voltage-gated calcium channels.
Volatile Anesthetic Preconditioning Present in the Invertebrate Caenorhabditis elegans
Authors: Jia Baosen , Crowder C Michael 
Published: March 2009

Background
Volatile anesthetics (VAs) have been found to induce a delayed protective response called preconditioning to subsequent hypoxic/ischemic injury. VA preconditioning has been primarily studied in canine and rodent heart. A more genetically tractable model of VA preconditioning would be extremely useful. Here, the authors report the development of the nematode Caenorhabditis elegans as a model of VA preconditioning.

Methods
Wild-type and mutant C. elegans were exposed to isoflurane, halothane, or air under otherwise identical conditions. After varying recovery periods, the animals were challenged with hypoxic, azide, or hyperthermic incubations. After recovery from these incubations, mortality was scored.

Results
Isoflurane- and halothane-preconditioned animals had significantly reduced mortality to all three types of injuries compared with air controls. Concentrations as low as 1 vol% isoflurane (0.64 mm) and halothane (0.71 mm) induced significant protection. The onset and duration of protection after anesthetic were 6 and 9 h, respectively. A mutation that blocks inhibition of neurotransmitter release by isoflurane did not attenuate the preconditioning effect. A loss-of-function mutation of the Apaf-1 homolog CED-4 blocked the preconditioning effect of isoflurane, but mutation of the downstream caspase CED-3 did not.

Conclusions
Volatile anesthetic preconditioning extends beyond the vertebrate subphylum. This markedly broadens the scope of VA preconditioning and suggests that its mechanisms are widespread across species and is a fundamental and evolutionarily conserved cellular response. C. elegans offers a means to dissect genetically the mechanism for VA preconditioning as illustrated by the novel finding of the requirement for the Apaf-1 homolog CED-4.
Vascular Remodeling Protects against Ventilator-induced Lung Injury in the In Vivo Rat
Authors: Kornecki Alik , Engelberts Doreen , McNamara Patrick , Jankov Robert P. , McCaul Conán , Ackerley Cameron , Post Martin , Kavanagh Brian P. 
Published: March 2009

Background
The role of the pulmonary vasculature in the pathogenesis of ventilator-induced lung injury is not well established. In this study, the authors investigated the effect of vascular remodeling due to chronic pulmonary hypertension on susceptibility to ventilator-induced lung injury. The authors hypothesized that the enhanced vascular tensile strength associated with pulmonary vascular remodeling would protect against ventilator-induced lung injury.

Methods
Chronic pulmonary arterial hypertension was induced in rats by exposure to hypoxia for 28 days and was confirmed by demonstration of right ventricular hypertrophy. Normotensive and hypertensive groups of rats (as well as a group in which pulmonary hypertension was acutely reversed with a Rho-kinase inhibitor, Y-27632) were exposed to injurious ventilation (respiratory rate 30 min, 30/0 cm H2O) for 90 min. Lung injury was assessed by change in lung mechanics, oxygenation, edema development, and cytokine levels. Electron microscopy was used to examine vascular structure in additional animals.

Results
Injurious ventilation caused significant lung injury (lung compliance, oxygenation, pulmonary edema) in the normotensive controls, but not in the presence of pulmonary hypertension; acute reversal of pulmonary hypertension did not alter the lessened susceptibility to ventilator-induced lung injury. Electron microscopy demonstrated capillary endothelial and epithelial breaks in injuriously ventilated normotensive controls that were not seen with pulmonary hypertension, whether or not the pulmonary hypertension was acutely reversed.

Conclusions
Vascular remodeling induced by chronic pulmonary hypertension confers protection against the effects of injurious mechanical ventilation in vivo by a mechanism that may involve structural alterations rather than increased pulmonary artery pressure.
Lung Injury and Recovery in a Murine Model of Unilateral Acid Aspiration
Authors: Amigoni Maria , Bellani Giacomo , Scanziani Margherita , Masson Serge , Bertoli Elisa , Radaelli Enrico , Patroniti Nicolò , Di Lelio Alessandro , Pesenti Antonio , Latini Roberto 
Published: March 2009

Background
Acid aspiration is a complication of general anesthesia. Most animal models developed to define its pathophysiology have focused on the acute (< or =24 h) phase of the injury. The authors describe a model of acid aspiration allowing the study of this type of lung injury over time.

Methods
The authors instilled hydrochloric acid (0.1 m, 1.5 ml/kg) or normal saline in the right bronchus of mice. Lung injury was evaluated at 6 h, 12 h, 24 h, and 2 weeks by assessing arterial blood gases, respiratory system compliance, lung wet weight normalized by body weight, lung myeloperoxidase activity, and histology. Twelve hours and 2 weeks after injury, a computed tomography scan was obtained.

Results
In the hydrochloric acid group, arterial oxygen tension decreased (P < 0.05) at 12 and 24 h, whereas it recovered at 2 weeks; respiratory system compliance was lower both at 24 h and 2 weeks (P < 0.05). Lung weight increased at 12 and 24 h (P < 0.05). Myeloperoxidase activity peaked between 6 and 12 h. Computed tomography at 12 h showed that almost 30% of the injured lung was abnormally aerated. Although reduced, the abnormalities were still present at 2 weeks as confirmed by a fibrotic scar well evident at histologic examination.

Conclusion
The authors characterized a murine model of regional acid aspiration allowing long-term survival. Despite a partial recovery, at 2 weeks the injury persisted, with evidence of fibrosis and lung compliance reduction. This long-term, low-mortality model seems suitable for assessment of the effects of different therapies on lung injury and repair.
Randomized Prospective Study Comparing the Laryngeal Tube Suction II with the ProSeal ™ Laryngeal Mask Airway in Anesthetized and Paralyzed Patients
Authors: Kikuchi Tatsuaki , Kamiya Yoshinori , Ohtsuka Tsuyoshi , Miki Tomoko , Goto Takahisa 
Published: March 2009

Background
The Laryngeal Tube Suction II (LTSII; VBM, Medizintechnik, Sulz, Germany) is a recent revision of the Laryngeal Tube Suction. This study compared insertion and ventilation profiles of the LTSII and the ProSeal Laryngeal Mask Airway (PLMA; Laryngeal Mask Company, Henley-on-Thames, United Kingdom) in anesthetized and paralyzed patients.

Methods
One hundred adult male patients were randomly allocated to an LTSII or PLMArade mark group. The rate of successful insertion, insertion time, airway leak pressure at a cuff pressure of 60 cm H2O, tidal volume during pressure-controlled ventilation, incidence of gas leakage with cuff pressure reduced and with the shaft inclined, position of LTSII under fluoroscopic observation, and postoperative airway morbidity were determined.

Results
Insertion was successful in 37 and 48 of 50 patients with LTSII and PLMA, respectively (P = 0.002), with similar insertion times. Tidal volume was lower with LTSII than with PLMA. Median airway leak pressures of LTSII and PLMA were 16 and 21 cm H2O, respectively (P = 0.006). Gas leakage around the cuff was observed more frequently with LTSII than with PLMA when the cuff pressure was reduced or the shaft of the device inclined. The position of LTSII varied significantly and did not statistically correlate with patient height. Postoperative airway-related morbidity was not significantly different. Finally, tracheal misplacement of LTSII occurred in 5 of 50 patients (10%), but ventilation was possible in 4 of them, and misplacement was identified only after fluoroscopic examination was performed.

Conclusion
Airway management with LTSII is inferior to that with PLMA.
Temporal Effects of Topical Morphine Application on Cutaneous Wound Healing
Authors: Rook Jerri M. , Hasan Wohaib , McCarson Kenneth E. 
Published: March 2009

Background
Studies have shown that topical administration of exogenous opioid drugs impairs wound healing by inhibiting the peripheral release of neuropeptides, thereby inhibiting neurogenic inflammation. This delay is immediate and peaks during the first days of wound closure. This study examined the effects of topical morphine treatment in a cutaneous wound healing model in the rat.

Methods
Full-thickness 4-mm-diameter wounds were placed on the periscapular region of rats that subsequently received twice-daily topical applications of IntraSite Gel (Smith+Nephew, Hull, United Kingdom) alone or gel infused with 5 mm morphine sulfate on days 0-3 or 4-10 postwounding or throughout the time course. Wound tissue was taken on days 1, 3, 5, 8, and 18 postwounding and immunostained for myofibroblast and macrophage markers or stained with hematoxylin and eosin.

Results
Delays in wound closure observed during morphine application on days 0-3 postwounding mimicked those seen in wounds treated with morphine throughout the entire healing process. However, no significant delays in closure were seen in wounds treated with morphine beginning on day 4 postwounding. Treatment of wounds with morphine significantly reduced the number of myofibroblasts and macrophages in the closing wound. In addition, morphine application resulted in decreases in skin thickness and an increase in residual scar tissue in healed skin.

Conclusions
These findings demonstrate the time-dependent and persistent nature of the detrimental effects of topical morphine on cutaneous wound healing. The data identify specific limitations that could be ameliorated to optimize topical opioid administration as an analgesic therapeutic strategy in the treatment of painful cutaneous wounds.
Total Intravenous Anesthesia Including Ketamine versus Volatile Gas Anesthesia for Combat-related Operative Traumatic Brain Injury
Authors: Grathwohl Kurt W. , Black Ian H. , Spinella Phillip C. , Sweeney Jason , Robalino Joffre , Helminiak Joseph , Grimes Jamie , Gullick Richard , Wade Charles E. 
Published: March 2009

Background
Traumatic brain injury is a leading cause of death and severe neurologic disability. The effect of anesthesia techniques on neurologic outcomes in traumatic brain injury and potential benefits of total intravenous anesthesia (TIVA) compared with volatile gas anesthesia (VGA), although proposed, has not been well evaluated. The purpose of this study was to compare TIVA versus VGA in patients with combat-related traumatic brain injury.

Methods
The authors retrospectively reviewed 252 patients who had traumatic brain injury and underwent operative neurosurgical intervention. Statistical analyses, including propensity score and matched analyses, were performed to assess differences between treatment groups (TIVA vs. VGA) and good neurologic outcome.

Results
Two hundred fourteen patients met inclusion criteria and were analyzed; 120 received VGA and 94 received TIVA. Good neurologic outcome (Glasgow Outcome Score 4-5) and decreased mortality were associated with TIVA compared with VGA (75% vs. 54%; P = 0.002 and 5% vs. 16%; P = 0.02, respectively). Multivariate logistic regression found admission Glasgow Coma Scale score of 8 or greater (odds ratio, 13.3; P < 0.001) and TIVA use (odds ratio, 2.3; P = 0.05) to be associated with good neurologic outcomes. After controlling for confounding factors using propensity analysis and repeated one-to-one matching of patients receiving TIVA with those receiving VGA with regard to Injury Severity Score, Glasgow Coma Scale score, base deficit, Head Abbreviated Injury Score, and craniectomy or craniotomy, the authors could not find an association between treatment and neurologic outcome.

Conclusion
Total intravenous anesthesia often including ketamine was not associated with improved neurologic outcome compared with VGA. Multiple confounders limit conclusions that can be drawn from this retrospective study.
Cholinesterase Inhibitor Donepezil Dilates Cerebral Parenchymal Arterioles via the Activation of Neuronal Nitric Oxide Synthase
Authors: Nakahata Katsutoshi , Kinoshita Hiroyuki , Hama-Tomioka Keiko , Ishida Yuko , Matsuda Naoyuki , Hatakeyama Noboru , Haba Masanori , Kondo Toshikazu , Hatano Yoshio 
Published: March 2009

Background
An acetylcholinesterase inhibitor donepezil currently is used to treat patients with Alzheimer disease. However, its direct effect on cerebral blood vessels has not been evaluated. The present study was designed to examine whether donepezil induces acute cerebral arteriolar dilation and whether neuronal nitric oxide synthase contributes to this vasodilator response.

Methods
Brain slices were obtained from neuronal nitric oxide synthase knock-out or C57BL/6J strain (control) mice as well as Wistar rats. Parenchymal arterioles were monitored using videomicroscopy. During constriction to prostaglandin F2alpha (5 x 10 m), donepezil (10-10 m) or acetylcholine (10-10 m) was added. In some experiments, brain slices were treated with a nonselective or a selective nitric oxide synthase inhibitor (N-nitro-L-arginine methyl ester [10 m] and S-methyl-L-thiocitrulline [10 m], respectively). An immunohistochemical analysis was performed using antibodies for neuronal nitric oxide synthase and acetylcholinesterase.

Results
Acetylcholine concentration-dependently dilated rat parenchymal arterioles, while S-methyl-L-thiocitrulline as well as N-nitro-L-arginine methyl ester completely abolished this response. Donepezil produced arteriolar dilation, which was inhibited by S-methyl-L-thiocitrulline or N-nitro-L-arginine methyl ester. Donepezil failed to induce arteriolar dilation in the brain slice from the neuronal nitric oxide synthase knock-out mice. Immunohistochemical analysis revealed spatial relationship between neuronal nitric oxide synthase and acetylcholinesterase in the arteriolar wall.

Conclusions
Donepezil produces acute vasodilation induced by a selective activation of neuronal nitric oxide synthase in the cerebral parenchymal arterioles. This agent may be capable of enhancing this enzymatic activity directly or via acetylcholinesterase existing on the arteriolar wall.
Greater Incidence of Emergence Agitation in Children after Sevoflurane Anesthesia as Compared with Halothane
Authors: Kuratani Norifumi , Oi Yumiko 
Published: March 2009

Background
Sevoflurane is a popular inhalational anesthetic for general anesthesia in children. The higher incidence of emergence agitation has been suspected after sevoflurane anesthesia as compared with halothane, whereas some controlled studies showed conflicting results. In this report, the authors performed a meta-analysis of randomized controlled trials to compare the incidence of emergence agitation in children after sevoflurane or halothane anesthesia.

Methods
A comprehensive literature search was conducted to identify clinical trials that compared the incidence of emergence agitation in children anesthetized with sevoflurane versus halothane. Two reviewers independently assessed each report to meet the authors inclusion criteria and extracted data. The data from each trial were combined using the Mantel-Haenszel fixed-effect model to calculate the pooled odds ratio and 95% confidence interval. Funnel plots were used to assess publication bias. Subgroup analysis was used to clarify the effects of age, surgical procedure, pain treatment, and premedication on the incidence of emergence agitation.

Results
The authors identified 23 studies that met their inclusion criteria. Overall, 1,252 patients received sevoflurane and 1,111 had halothane. Heterogeneity of data was statistically refuted. The pooled odds ratio for all studies was 2.21, with a 95% confidence interval of 1.77-2.77 (P < 0.0001). Publication bias was not apparent in a funnel plot. All subgroup analyses showed a higher incidence of agitation after sevoflurane anesthesia.

Conclusions
This meta-analysis revealed that emergence agitation occurred more frequently with sevoflurane than with halothane anesthesia in children.
Inhalational Anesthetics Induce Cell Damage by Disruption of Intracellular Calcium Homeostasis with Different Potencies
Authors: Yang Hui , Liang Ge , Hawkins Brian J. , Madesh Muniswamy , Pierwola Andrew , Wei Huafeng 
Published: March 2009

Background
The authors hypothesized that inhalational anesthetics induced cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of inositol 1,4,5-trisphosphate (IP3) receptors, with isoflurane having greater potency than sevoflurane or desflurane.

Methods
The authors treated DT40 chicken B lymphocytes with total IP3 receptor knockout or their corresponding wild-type control cells with equipotent exposure to isoflurane, sevoflurane, and desflurane. The authors then determined the degree of cell damage by counting the percentage of annexin V- or propidium iodide-positively stained cells or measuring caspase-3 activity. They also studied the changes of calcium concentrations in the endoplasmic reticulum, cytosol, and mitochondria evoked by equipotent concentrations of isoflurane, sevoflurane, and desflurane in both types of DT40 cells.

Results
Prolonged use of 2 minimal alveolar concentration sevoflurane or desflurane (24 h) induced significant cell damage only in DT40 wild-type and not in IP3 receptor total knockout cells, but with significantly less potency than isoflurane. In accord, all three inhalational anesthetics induced significant decrease of calcium concentrations in the endoplasmic reticulum, accompanied by a subsequent significant increase in the cytosol and mitochondrial calcium concentrations only in DT40 wild-type and not in IP3 receptor total knockout cells. Isoflurane treatment showed significantly greater potency of effect than sevoflurane or desflurane.

Conclusion
Inhalational anesthetics may induce cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of IP3 receptors. Isoflurane has greater potency than sevoflurane or desflurane to cause calcium release from the endoplasmic reticulum and to induce cell damage.
Hyperestrogenemia Simulating Kennedy Disease
Authors: Luo Jin Jun 
Published: March 2009

ABSTRACT

A 71-year-old man developed clinical signs of Kennedy disease including dysarthria, dysphagia, palatal and oral mandibular fasciculations, lower-extremity weakness, gynecomastia, and testicular atrophy. Electrophysiologic studies showed sensory axonal polyneuropathy and chronic neurogenic changes of large-motor unit action potentials with decreased recruitment. Genetic analysis showed a normal 17-CAG repeat sequence. Laboratory studies showed an increased estrogen level of 180 to 220 pg/mL, probably related to his alcoholic fatty liver disease. Splenomegaly was present by ultrasound. The increased level of estrogen adversely affected estrogen-sensitive cells in breast, testicular, neuronal, and muscle cells, leading to the clinical phenotype.