bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arterial and Venous Pharmacokinetics of Ropivacaine with and without Epinephrine after Thoracic Paravertebral Block
Authors: Karmakar Manoj K. , Ho Anthony M.-H. , Law Bonita K. , Wong April S. Y. , Shafer Steven L. , Gin Tony 
Published: September 2005

Background
Animal and volunteer studies indicate that ropivacaine is associated with less neurologic and cardiac toxicity than bupivacaine. Ropivacaine may offer advantages when used for thoracic paravertebral block. This study was designed to describe the pharmacokinetics of ropivacaine after thoracic paravertebral block.

Methods
Twenty female patients undergoing elective unilateral breast surgery were randomly assigned to receive a single bolus thoracic paravertebral injection of 2 mg/kg ropivacaine, with or without 5 mug/ml epinephrine. Simultaneous arterial and venous blood samples were obtained for plasma ropivacaine assay. Data were analyzed with NONMEM, using two possible absorption models: conventional first-order absorption and absorption following the inverse gaussian density function.

Results
Epinephrine reduced the peak plasma concentrations and delayed the time of peak concentration of ropivacaine in both the arterial and venous blood. The time course of drug input into the systemic circulation was best described by two inverse gaussian density functions. The median bioavailability of the rapid component was approximately 20% higher when epinephrine was not used. The mean absorption times were 7.8 min for the rapid absorption phase and 697 min for the slow absorption phase, with wide dispersion of the absorption function for the acute phase. The half-time of arterial-venous equilibration was 1.5 min.

Conclusion
The absorption of ropivacaine after thoracic paravertebral block is described by rapid and slow absorption phases. The rapid phase approximates the speed of intravenous administration and accounts for nearly half of ropivacaine absorption. The addition of 5 mug/ml epinephrine to ropivacaine significantly delays its systemic absorption and reduces the peak plasma concentration.
Synthetic Colloids Attenuate Leukocyte-Endothelial Interactions by Inhibition of Integrin Function
Authors: Nohé Boris , Johannes Tanja , Reutershan Jörg , Rothmund Albert , Haeberle Helene A. , Ploppa Annette , Schroeder Torsten H. , Dieterich Hans-Juergen 
Published: September 2005

Background
It has been suspected that synthetic colloids may interfere with leukocyte adhesion by down-regulation of endothelial cell adhesion molecules. Although inhibition of endothelial inflammation might reduce leukocyte-related tissue injury, the same mechanism may be detrimental for host defense during severe infection. Regarding the widespread use of colloids, the authors performed a laboratory investigation to determine the mechanisms by which synthetic colloids interfere with leukocyte-endothelial interactions.

Methods
Adhesion molecule expression on native and cytokine-activated endothelium from umbilical veins was measured after pretreatment with gelatin and various preparations of dextran or hydroxyethyl starch. Inhibition of neutrophil adhesion to activated endothelium was examined in a flow chamber by perfusion of untreated and colloid-treated neutrophils over colloid-pretreated endothelium at 2 dyn/cm. Comparisons were made between untreated controls, colloid-pretreated endothelium, and colloid-cotreated neutrophils.

Results
Intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, and P-selectin were not attenuated by any colloid. Accordingly, colloid pretreatment of endothelium alone did not reduce neutrophil adhesion. In contrast, when neutrophils were cotreated by addition of colloids to the perfusate immediately before perfusion, adhesion decreased by 31-51% (P < 0.05) regardless of the colloid type. As indicated by the twofold increased rolling fractions, this reduction was due to an inhibition of neutrophil integrins.

Conclusions
This study shows that synthetic colloids inhibit neutrophil adhesion by a neutrophil-dependent mechanism rather than interfering with endothelial cell activation. This suggests that inhibition of leukocyte sequestration by volume support is a common and transient phenomenon depending on the colloid concentration in plasma.
Volatile Anesthetics Bind Rat Synaptic Snare Proteins
Authors: Nagele Peter , Mendel J Brett , Placzek William J. , Scott Barbara A. , d'Avignon D André , Crowder C Michael 
Published: September 2005

Background
Volatile general anesthetics (VAs) have a number of synaptic actions, one of which is to inhibit excitatory neurotransmitter release; however, no presynaptic VA binding proteins have been identified. Genetic data in Caenorhabditis elegans have led to the hypothesis that a protein that interacts with the presynaptic protein syntaxin 1A is a VA target. Motivated by this hypothesis, the authors measured the ability of syntaxin 1A and proteins that interact with syntaxin to bind to halothane and isoflurane.

Methods
Recombinant rat syntaxin 1A, SNAP-25B, VAMP2, and the ternary SNARE complex that they form were tested. Binding of VAs to these proteins was detected by F-nuclear magnetic resonance relaxation measurements. Structural alterations in the proteins were examined by circular dichroism and ability to form complexes.

Results
Volatile anesthetics did not bind to VAMP2. At concentrations in the clinical range, VAs did bind to SNAP-25B; however, binding was detected only in preparations containing SNAP-25B homomultimers. VAs also bound at clinical concentrations to both syntaxin and the SNARE complex. Addition of an N-terminal His6 tag to syntaxin abolished its ability to bind VAs despite normal secondary structure and ability to form SNARE complexes; thrombin cleavage of the tag restored VA binding. Thus, the VA binding site(s) has structural requirements and is not simply any alpha-helical bundle. VAs at supraclinical concentrations produced an increase in helicity of the SNARE complex; otherwise, VA binding produced no gross alteration in the stability or secondary structure of the SNARE complex.

Conclusion
SNARE proteins are potential synaptic targets of volatile anesthetics.
Morphine Inhibits Acetylcholine Release in Rat Prefrontal Cortex When Delivered Systemically or by Microdialysis to Basal Forebrain
Authors: Osman Nadir I. , Baghdoyan Helen A. , Lydic Ralph 
Published: September 2005

Background
Cortical acetylcholine originates in the basal forebrain and is essential for maintaining normal cognition and arousal. Morphine impairs these cholinergically mediated cortical functions. The current study tested the hypothesis that morphine decreases prefrontal cortical acetylcholine release by acting at the level of the basal forebrain.

Methods
Adult male Sprague-Dawley rats (n = 18) were anesthetized with isoflurane. One microdialysis probe was placed in the substantia innominata region of the basal forebrain and perfused with Ringer's solution (control) followed by one concentration of morphine (1, 10, 100, or 1,000 microm) or morphine (1,000 microm) plus naloxone (100 microm). A second microdialysis probe was placed in the prefrontal cortex for measuring acetylcholine. In a second series of experiments, rats (n = 6) were implanted with electrodes for recording states of arousal, a guide cannula positioned above the prefrontal cortex for inserting a microdialysis probe, and an indwelling jugular vein catheter. The effects of administering intravenous morphine (30 mg/kg) versus normal saline (0.9%) on prefrontal cortical acetylcholine release, cortical electroencephalographic power, and behavior were quantified.

Results
Dialysis delivery of morphine to the substantia innominata caused a concentration-dependent, naloxone-sensitive decrease in acetylcholine release within the prefrontal cortex. The maximal decrease in acetylcholine was 36.3 +/- 11.5%. Intravenous morphine administration significantly decreased cortical acetylcholine release, increased electroencephalographic power in the 0.5- to 5-Hz range, and eliminated normal wakefulness.

Conclusion
Morphine causes obtundation of arousal and may cause cognitive impairment by acting at the level of the substantia innominata to disrupt cortical cholinergic neurotransmission.
Inhibition of Kv4.3/KChIP2.2 Channels by Bupivacaine and Its Modulation by the Pore Mutation Kv4.3V401I
Authors: Solth Anna , Siebrands Cornelia C. , Friederich Patrick 
Published: September 2005

Background
The transient outward current Ito is an important repolarizing K current in human ventricular myocardium mediated by Kv4.3 and KChIP2.2 subunits. Inhibition of Ito by amino-amide local anesthetics may be involved in severe cardiotoxic side effects. This study elucidates the molecular mechanisms of bupivacaine interaction with complexes formed by Kv4.3 and KChIP2.2 as well as the modulatory effect of KChIP2.2. For this purpose, the pharmacologic effects of bupivacaine on Kv4.3wt/KChIP2.2 channels and on the pore mutant Kv4.3V401I were investigated.

Methods
Kv4.3/KChIP2.2 cDNA was transiently expressed in Chinese hamster ovary cells. Site-directed mutagenesis and patch clamp experiments were performed to analyze the effects of bupivacaine on wild-type and mutant channels.

Results
Inhibition of Kv4.3wt/KChIP2.2 channels by bupivacaine was concentration-dependent and reversible. The IC50s for inhibition of the charge conducted by Kv4.3wt/KChIP2.2 channels by bupivacaine and levobupivacaine were 55 +/- 8 and 50 +/- 5 microm, respectively. The local anesthetic accelerated macroscopic current decline of Kv4.3wt/KChIP2.2 and slowed recovery from inactivation without altering steady state inactivation. KChIP2.2 altered the response of Kv4.3wt channels to bupivacaine and bupivacaine modulated KChIP2.2 effects on Kv4.3wt channels. The pore mutation V401I slowed macroscopic current decline of Kv4.3 channels and recovery from inactivation, and it diminished modulation of gating by KChIP2.2. Bupivacaine inhibition of Kv4.3V401I resembled Kv4.3wt and was not changed by coexpression of KChIP2.2.

Conclusions
These results indicate that bupivacaine blocks Kv4.3/KChIP2.2 channels from the open state. They furthermore give structural evidence that amino-amide local anesthetics interfere with the effects of KChIP2.2 on Kv4.3 by an indirect mechanism.
Estimation of Errors in Determining Intrathoracic Blood Volume Using the Single Transpulmonary Thermal Dilution Technique in Hypovolemic Shock
Authors: Nirmalan Mahesh , Willard Terrance M. , Edwards Dennis J. , Little Rod A. , Dark Paul M. 
Published: September 2005

Background
The transpulmonary thermal dilution technique has been widely adopted for monitoring cardiac preload and extravascular lung water in critically ill patients. This method assumes intrathoracic blood volume (ITBV) to be a fixed proportion of global end-diastolic volume (GEDV). This study determines the relation between GEDV and ITBV under normovolemic and hypovolemic conditions and quantifies the errors in estimating ITBV.

Methods
Nineteen pigs allocated to control (n = 9) and shock (n = 10) groups were studied. Shock was maintained for 60 min followed by volume resuscitation. The dual dye-thermal dilution technique was used to measure GEDV and ITBV (ITBVm) at baseline (time 0), shock phase (30 and 90 min), and after resuscitation (150 min). The regression equations estimated from paired GEDV and ITBVm measurements under normovolemic and hypovolemic conditions were used to estimate ITBV from the corresponding GEDV, and the estimation errors were quantified. A more simplified equation, used in a commercially available clinical monitor (ITBV = 1.25 x GEDV), was then used to estimate ITBV.

Results
The regression equation in the control group was ITBVm = 1.21 x GEDV + 99 (r = 0.89, P < 0.0001) and in the shock group at 30 and 90 min was ITBVm = 1.45 x GEDV + 0.6 (r = 0.95, P < 0.0001). The 95% confidence interval for the y-intercept was relatively wide, ranging from 31 to 168 and -47 to 49, respectively, for the two equations. The equation estimated in the control group led to overestimation of ITBV and a significant (P < 0.05) increase in errors in the shock group at 30 and 90 min. Errors in estimating ITBV using the simplified commercial algorithm were less than 15% under normovolemic and hypovolemic conditions.

Conclusions
The linear relation between GEDV and ITBV is maintained in hypovolemic shock. Even though the relation between GEDV and ITBV is influenced by circulatory volume and cardiac output, the mean errors in predicting ITBV were small and within clinically tolerable limits.
Short Hairpin RNA–mediated Selective Knockdown of NaV1.8 Tetrodotoxin-resistant Voltage-gated Sodium Channel in Dorsal Root Ganglion Neurons
Authors: Mikami Maya , Yang Jay 
Published: September 2005

Background
Voltage-gated sodium channels comprise a family of closely related proteins, each subserving different physiologic and pathologic functions. NaV1.8 is an isoform of voltage-gated sodium channel implicated in the pathogenesis of inflammatory and neuropathic pain, but currently, there is no isoform-specific inhibitor of any voltage-gated sodium channels. The authors explored the possibility of short hairpin RNA-mediated selective knockdown of NaV1.8 expression.

Methods
DNA constructs designed to transcribe short hairpin RNA targeting NaV1.8 were created and incorporated into recombinant lentiviruses. The virus-induced selective knockdown of NaV1.8 was examined at the protein, messenger RNA, and functional levels using Western blot, immunohistochemistry, reverse-transcription polymerase chain reaction, and patch clamp electrophysiology.

Results
Transduction of HEK293 cells stably expressing NaV1.8 or primary dorsal root ganglion neurons with lentivirus expressing short hairpin RNA resulted in the knockdown of NaV1.8 protein and messenger RNA concentrations. Whole cell patch clamp recordings confirmed decrease in the NaV1.8-mediated current density without changes in other biophysical properties.

Conclusions
A selective knockdown of NaV1.8 expression in dorsal root ganglion neurons can be attained by short hairpin RNA delivered with lentivirus. This method may provide a new gene therapy approach to controlling neuronal hyperexcitability and pathologic pain.
Role for Cyclooxygenase 2 in the Development and Maintenance of Neuropathic Pain and Spinal Glial Activation
Authors: Takeda Kenji , Sawamura Shigehito , Tamai Hisayoshi , Sekiyama Hiroshi , Hanaoka Kazuo 
Published: September 2005

Background
Lines of evidence have indicated that cyclooxygenase 2 plays a role in the pathophysiology of neuropathic pain. However, the site and mechanism of its action are still unclear. Spinal glia has also been reported to mediate pathologic pain states. The authors evaluated the effect of continuous intrathecal or systemic cyclooxygenase-2 inhibitor on the development and maintenance of neuropathic pain and glial activation in a spinal nerve ligation model of rats.

Methods
Continuous intrathecal infusion of meloxicam (32 or 320 mug . kg . day) or saline was started immediately after L5-L6 spinal nerve ligation. Mechanical allodynia and thermal hyperalgesia were evaluated on days 4 and 7 postoperatively. Spinal astrocytic activation was evaluated with glial fibrially acidic protein immunoreactivity on day 7. In other groups of rats, continuous intrathecal meloxicam was started 7 days after spinal nerve ligation, and effects on established neuropathic pain and glial activation were evaluated. Last, effects of continuous systemic meloxicam (16 mg . kg . day) on existing neuropathic pain and glial activation were examined.

Results
Intrathecal meloxicam prevented the development of mechanical allodynia and thermal hyperalgesia induced by spinal nerve ligation. It also inhibited spinal glial activation responses. In contrast, when started 7 days after the nerve ligation, intrathecal meloxicam did not reverse established neuropathic pain and glial activation. Systemic meloxicam started 7 days after ligation partially reversed neuropathic behaviors but not glial activation.

Conclusions
Spinal cyclooxygenase 2 mediates the development but not the maintenance of neuropathic pain and glial activation in rats. Peripheral cyclooxygenase 2 plays a part in the maintenance of neuropathic pain.
Nitrous Oxide Revisited
Authors: Richebé Philippe , Rivat Cyril , Creton Cyril , Laulin Jean-Paul , Maurette Pierre , Lemaire Marc , Simonnet Guy 
Published: September 2005

Background
Although opioids are unsurpassed analgesics for surgery, they also induce an N-methyl-D-aspartate-dependent enhancement of postoperative hyperalgesia. Because nitrous oxide (N2O) has anti-N-methyl-D-aspartate properties, the purpose of this study was to evaluate nitrous oxide ability to prevent such an opioid-induced hyperalgesia in rats.

Methods
First, preventive effects of 50/50% N2O-O2 on the development of delayed hyperalgesia observed after inflammatory pain (hind paw carrageenan injection on D0) were examined for several days. Second, the ability of nitrous oxide (10-40%) to limit opioid-induced hyperalgesia induced by fentanyl was evaluated in nonsuffering rats. Third, antihyperalgesic effects of various nitrous oxide concentrations (20-50%) were assessed in both inflammatory and incisional pain models in fentanyl-treated rats (4 x 100 microg/kg subcutaneously). Finally, the analgesic effect of a single dose of morphine was evaluated 24 h after fentanyl administration and nitrous oxide (D0) to assess its preventive effect on acute morphine tolerance in both nonsuffering and hind paw-incised rats.

Results
When applied on D0, nitrous oxide reduced delayed hyperalgesia induced by inflammation. Exposure to nitrous oxide on D0 also reduced opioid-induced hyperalgesia in nonsuffering rats in a dose-dependent manner. In fentanyl-treated rats with inflammatory or incisional pain, nitrous oxide strongly limited both magnitude and duration of hyperalgesia. Moreover, nitrous oxide exposure on D0 opposed development of acute tolerance to analgesic effects of morphine administered on D1 in both nonsuffering and incised fentanyl-treated rats.

Conclusions
Nitrous oxide, an N-methyl-D-aspartate receptor antagonist, prevented the enhancement of pain sensitivity induced by both nociceptive inputs and fentanyl and opposed acute morphine tolerance. Results suggest that perioperative nitrous oxide use reduces exaggerated postoperative pain and morphine consumption.
What is supportive when an adult next‐of‐kin is in critical care?
Authors: Johansson Ingrid , Fridlund Bengt , Hildingh Cathrine 
Published: October 2005

AbstractThere is little documented knowledge about what is supportive from the perspective of relatives with a critically ill next‐of‐kin in the intensive care unit (ICU). The aim of the present study was to generate a theoretical understanding of what relatives experience as supportive when faced with the situation of having an adult next‐of‐kin admitted to critical care. The study was designed using a grounded theory methodology. Interviews were conducted with 29 adult relatives of adult ICU patients in southwest Sweden. Relatives described the need to be empowered and that support was needed to enable them to use both internal and external resources to cope with having a next‐of‐kin in critical care. To achieve empowerment, the relatives described the need to trust in oneself, to encounter charity and to encounter professionalism. The findings can contribute understanding and sensitivity to the situation of the relatives as well as indicating what form social support should take. It is essential that healthcare professionals understand how important it is for relatives to have control over their vulnerable situation and that they also reflect upon how they would like to be treated themselves in a similar situation. Recommendations for future practice are presented.
Impacts of irrigation on fisheries in rain‐fed rice‐farming landscapes
Authors: KHOA SOPHIE NGUYEN , LORENZEN KAI , GARAWAY CAROLINE , CHAMSINHG BOUNTHANOM , SIEBERT DARRELL , RANDONE MAURO 
Published: September 2005

Summary

Expanding irrigation development threatens the productive and diverse fisheries of rain‐fed rice‐farming landscapes. Environmental management of irrigation can minimize negative impacts on fisheries, but its effectiveness is constrained by a lack of reliable information on the nature and magnitude of impacts.
To quantify the impacts of small‐ to medium‐scale irrigation schemes on aquatic habitat availability, fish catches, species richness and ecological composition of fish assemblages in these landscapes, we conducted a field study in Laos. The observational study was replicated at irrigation scheme level, covering 10 weir and 10 dam irrigation schemes paired with non‐impacted control sites.
Weir schemes had no significant impact on aquatic habitat, but caused a significant decline (−36%) in fish catches that was only partly explained by a reduction in fishing effort. Weirs had no effect on species richness, but were associated with a significant increase (+17%) in the relative abundance of omnivores.
Dam irrigation schemes significantly reduced riverine habitat area, and increased lacustrine and dry‐season rice‐field areas. Dams led to a marked redistribution of catch and fishing effort from non‐reservoir habitats into reservoirs, but no overall change in catch or effort occurred. The redistribution reflected a response to fishing opportunities in the reservoir, rather than a loss of productivity in non‐reservoir habitats. No significant impacts were detected on fish species richness or the relative abundance of functional feeding groups.
Overall impacts of irrigation on fisheries were related mostly to changes in fishing effort, rather than ecological effects on the resources. The unexpectedly moderate level of ecological impacts may reflect compensatory effects at the landscape level and the fact that rice fields, which dominated the wet‐season habitat, continued to be managed as rain‐fed deep‐water systems even where dry‐season irrigation had been developed.
Synthesis and applications. Small‐ to medium‐scale irrigation schemes in rain‐fed rice‐farming landscapes have only moderate impacts on fisheries, which remain productive and diverse. Changes in agricultural practices in the wet season are likely to have greater effects on fisheries than dry‐season irrigation.