bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of adenosine‐induced airways obstruction in allergic guinea pigs
Authors: Keir Sandra , Boswell‐Smith Victoria , Spina Domenico , Page Clive 
Published: January 2006

Inhaled adenosine induces airway obstruction in asthmatic but not healthy subjects, a phenomenon that is also observed in various animal species when they are immunised to a relevant antigen, but which does not occur in naïve animals. The purpose of this study was to investigate the mechanisms of airway responsiveness to adenosine receptor agonists in anaesthetised allergic guinea pigs.
Inhaled adenosine 5′‐monophosphate (AMP), the A1‐selective adenosine receptor agonist N6‐cyclopentyladenosine (CPA) and ovalbumin all caused airway obstruction in allergic guinea pigs, but not naïve animals, as assessed by changes in total lung resistance. In contrast, the A2a‐selective (CGS 21680; 2‐p‐(2‐carboxyethyl)phenethylamino‐5′‐N‐ethylcarboxoamido adenosine) and A3‐selective (IB‐MECA; 1‐deoxy‐1‐[6‐[[3‐iodophenyl)‐methyl]amino]‐9H‐purin‐9‐yl]‐N‐methyl‐β‐D‐ribofuranuronamide) adenosine receptor agonists failed to elicit airway obstruction in passively sensitised guinea pigs.
Airway obstruction induced by AMP or CPA was not inhibited by the H1 receptor antagonist, mepyramine (1 mg kg−1) in passively sensitised guinea‐pigs. In contrast, airway obstruction to ovalbumin was significantly inhibited by this antagonist.
Airway obstruction induced by AMP and CPA was significantly inhibited in sensitised animals chronically treated with capsaicin. In contrast, airway obstruction to ovalbumin was not inhibited by this treatment.
Airway obstruction induced by AMP, CPA and ovalbumin was significantly inhibited following bilateral vagotomy or pharmacological treatment with atropine (2 mg kg−1).
Airway obstruction to CPA was inhibited by the adenosine A1 receptor antagonist, 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX: 0.1–1 mg kg−1). In contrast, airway obstruction to ovalbumin was not inhibited by this treatment.
These observations provide evidence indicating that AMP and CPA may induce airway obstruction in sensitised guinea pigs by a mechanism unrelated to histamine release from mast cells, but is mediated via an adenosine A1‐receptor‐dependent mechanism. The inhibition of AMP‐ and CPA‐induced airway obstruction by atropine, capsaicin and bilateral vagotomy suggests a neuronal‐dependent mechanism with the particular involvement of capsaicin‐sensitive nerves.

British Journal of Pharmacology (2006) 147, 720–728. doi:10.1038/sj.bjp.0706663
Differential Rho‐kinase dependency of full and partial muscarinic receptor agonists in airway smooth muscle contraction
Authors: Schaafsma Dedmer , Boterman Mark , De Jong Anne‐Margreet , Hovens Iris , Penninks Jelte‐Maarten , Nelemans S Adriaan , Meurs Herman , Zaagsma Johan 
Published: January 2006

In airway smooth muscle (ASM), full and partial muscarinic receptor agonists have been described to have large differences in their ability to induce signal transduction, including Ca2+‐mobilization. Despite these differences, partial agonists are capable of inducing a submaximal to maximal ASM contraction.
To further elucidate transductional differences between full and partial muscarinic receptor agonists, we investigated the contribution of Rho‐kinase (an important regulator of Ca2+‐sensitization) to methacholine‐, pilocarpine‐ and McN‐A‐343‐induced bovine tracheal smooth muscle (BTSM) contraction, using the selective Rho‐kinase inhibitor Y‐27632. In addition, we measured Ca2+‐mobilization and ‐influx in BTSM cells in response to these agonists in the absence and presence of Y‐27632.
Whereas treatment with Y‐27632 (1 μM) significantly decreased potency (pEC50) for all agonists, maximal contraction (Emax) was reduced by 23.4±2.8 and 50.4±7.9% for the partial agonists pilocarpine and McN‐A‐343, respectively, but was unaffected for the full agonist methacholine. However, Emax of methacholine became Rho‐kinase dependent after taking away its receptor reserve using the irreversible muscarinic receptor antagonist propylbenzilylcholine mustard.
Pilocarpine and McN‐A‐343 induced a very small Ca2+‐mobilization and ‐influx as compared to methacholine. In addition, an inverse relationship of these two parameters with the Rho‐kinase dependency was observed. Interestingly, no inhibitory effects of Y‐27632 were observed on Ca2+‐mobilization and‐influx for all three agonists, indicating that the effects of Y‐27632 on contraction are most likely on the level of Ca2+‐sensitization.
In conclusion, in contrast to the full agonist methacholine, the partial muscarinic receptor agonists pilocarpine and McN‐A‐343 are dependent on Rho‐kinase for their maximal contractile effects, presumably as a consequence of differences in transductional reserve, indicating an agonist‐dependent role for Rho‐kinase in ASM contraction. Moreover, an inverse relationship exists between Rho‐kinase dependency and both Ca2+‐mobilization and Ca2+‐influx for these agonists.

British Journal of Pharmacology (2006) 147, 737–743. doi:10.1038/sj.bjp.0706665
Compared pharmacology of human histamine H3and H4receptors: structure–activity relationships of histamine derivatives
Authors: Gbahou Florence , Vincent Ludwig , Humbert‐Claude Marie , Tardivel‐Lacombe Joel , Chabret Claude , Arrang Jean‐Michel 
Published: January 2006

Various histamine derivatives were investigated at the human H3receptor (H3R) and H4receptor (H4R) stably expressed in human embryonic kidney (HEK)‐293 cells using [125I]iodoproxyfan and [3H]histamine binding, respectively.In Tris buffer, [3H]histamine binding to membranes of HEK(hH4R) cells was monophasic (KDof 3.8±0.8 nM). In phosphate buffer, the Hill coefficient was decreased (nH=0.5±0.1) and a large fraction of the binding was converted into a low‐affinity component (KD=67±27 nM).The inhibition of [3H]histamine binding by two agonists, a protean agonist and five antagonists/inverse agonists confirms that the potency of many H3R ligands is retained or only slightly reduced at the H4R.Histamine derivatives substituted with methyl groups inα,βorNαposition of the side chain retained a nanomolar potency at the H3R, but their affinity was dramatically decreased at the H4R. With relative potencies to histamine of 282 and 0.13% at the H3R and H4R, respectively, (±)‐α,β‐dimethylhistamine is a potent and selective H3R agonist.Chiralα‐branched analogues exhibited a marked stereoselectivity at the H3R and H4R, the enantiomers with a configuration equivalent toL‐histidine being preferred at both receptors.The methylsubstitution of the imidazole ring was also studied. The relative potency to histamine of 4‐methylhistamine (4‐MeHA) at the H4R (67%) was similar to that reported at H2receptors but, owing to its high affinity at the H4R (Ki=7.0±1.2 nM) and very low potency at H1‐ and H3‐receptors, it can be considered as a potent and selective H4R agonist.On inhibition of forskolin‐induced cAMP formation, all the compounds tested, including 4‐MeHA, behaved as full agonists at both receptors. However, the maximal inhibition achieved at the H4R (∼−30%) was much lower than at the H3R (∼−80%). Thioperamide behaved as an inverse agonist at both receptors and increased cAMP formation with the same maximal effect (∼+25%).In conclusion, although the pharmacological profiles of the human H3R and H4R overlap, the structure–activity relationships of histamine derivatives at both receptors strongly differ and lead to the identification of selective compounds.British Journal of Pharmacology(2006)147, 744–754. doi:10.1038/sj.bjp.0706666
Mechanisms of 5‐aminolevulic acid ester uptake in mammalian cells
Authors: Rodriguez Lorena , Batlle Alcira , Di Venosa Gabriela , Battah Sinan , Dobbin Paul , MacRobert Alexander J , Casas Adriana 
Published: January 2006

The porphyrin precursor 5‐aminolevulinic acid (ALA) is being widely used in photodynamic therapy of cancer. Improvement in ALA delivery has been sought through the use of ALA derivatives, in particular the esterification of ALA with aliphatic alcohols, which in certain cases can improve cellular penetration and selectivity.
ALA uptake systems appear to be distinctive for each cell type. The LM3 mammary adenocarcinoma cell line takes ALA up by BETA transporters. In this work, we investigated ALA derivative transport systems through the inhibition of radiolabelled ALA uptake in the LM3 cells. We also performed inhibition studies of γ‐aminobutyric acid (GABA) uptake.
The more lipohilic ALA derivatives hexyl‐ALA and undecanoyl‐ALA inhibit ALA uptake, whereas methyl‐ALA, R, S‐ALA‐2‐(hydroxymethyl)tetrahydropyranyl ester and the dendron aminomethane tris methyl 5‐ALA does not inhibit ALA uptake. A similar pattern was found for GABA, except that the dendron inhibited GABA uptake. However, hexyl‐ALA and undecanoyl‐ALA are not taken up by BETA transporters, but by simple diffusion, although they still inhibit ALA uptake by binding to the cell membrane.
These results show that different modifications to the ALA molecule lead to different uptake mechanisms. Whereas ALA is taken up by BETA transporters, none of the ALA derivatives shares the same mechanism. Knowledge of the mechanisms of ALA derivatives entry into the cells is essential to understand and improve ALA‐mediated PDT and to the design of new ALA derivatives that may be taken up at a higher rate than ALA.

British Journal of Pharmacology (2006) 147, 825–833. doi:10.1038/sj.bjp.0706668
Injury and Liability Associated with Monitored Anesthesia Care
Authors: Bhananker Sanjay M. , Posner Karen L. , Cheney Frederick W. , Caplan Robert A. , Lee Lorri A. , Domino Karen B. 
Published: January 2006

Background
To assess the patterns of injury and liability associated with monitored anesthesia care (MAC) compared with general and regional anesthesia, the authors reviewed closed malpractice claims in the American Society of Anesthesiologists Closed Claims Database since 1990.

Methods
All surgical anesthesia claims associated with MAC (n = 121) were compared with those associated with general (n = 1,519) and regional (n = 312) anesthesia. A detailed analysis of MAC claims was performed to identify causative mechanisms and liability patterns.

Results
MAC claims involved older and sicker patients compared with general anesthesia claims (P < 0.025), often undergoing elective eye surgery (21%) or facial plastic surgery (26%). More than 40% of claims associated with MAC involved death or permanent brain damage, similar to general anesthesia claims. In contrast, the proportion of regional anesthesia claims with death or permanent brain damage was less (P < 0.01). Respiratory depression, after absolute or relative overdose of sedative or opioid drugs, was the most common (21%, n = 25) specific damaging mechanism in MAC claims. Nearly half of these claims were judged as preventable by better monitoring, including capnography, improved vigilance, or audible alarms. On-the-patient operating room fires, from the use of electrocautery, in the presence of supplemental oxygen during facial surgery, resulted in burn injuries in 20 MAC claims (17%).

Conclusion
Oversedation leading to respiratory depression was an important mechanism of patient injuries during MAC. Appropriate use of monitoring, vigilance, and early resuscitation could have prevented many of these injuries. Awareness and avoidance of the fire triad (oxidizer, fuel, and ignition source) is essential to prevent on-the-patient fires.
Ventilator-associated Pneumonia Leading to Acute Lung Injury after Trauma
Authors: Stéphan François , Mabrouk Nejma , Decailliot François , Delclaux Christophe , Legrand Patrick 
Published: January 2006

Background
Ventilator-associated pneumonia is a clear risk factor for acute lung injury which has been poorly described in trauma patients. This prospective study was undertaken to estimate the incidence of such ventilator-associated pneumonia leading to acute lung injury, the risk factors, and the associated morbidity and mortality in a group of multiple trauma patients.

Methods
Trauma patients who were mechanically ventilated and survived at least 24 h were included. Ventilator-associated pneumonia was confirmed by a bacterial culture of a blind protected telescoping catheter with at least 10 colony-forming units/ml of at least one pathogen. Episodes of acute lung injury were prospectively recorded.

Results
Ventilator-associated pneumonia was documented in 78 patients of the 175 included (44%) and led to the development of ventilator-associated pneumonia acute lung injury in 18 patients (23%). The sole independent risk factor for ventilator-associated pneumonia leading to acute lung injury was the presence of Haemophilus influenzae (hazard ratio, 8.8; 95% confidence interval, 2.7-28.6). Eleven (61%) of the 18 patients with ventilator-associated pneumonia leading to acute lung injury had development of a ventilator-associated pneumonia recurrence, as compared with 20 (33%) of the 60 patients with ventilator-associated pneumonia alone (P = 0.03). Seven (39%) of the 18 trauma patients with ventilator-associated pneumonia leading to acute lung injury died, as compared with 9 (15%) of the 60 trauma patients with ventilator-associated pneumonia alone (P = 0.04).

Conclusion
Acute lung injury complicated the course of 15% of ventilator-associated pneumonia in trauma patients. H. influenzae seemed to be one of the most frequent bacteria involved and the sole risk factor identified. Occurrence of ventilator-associated pneumonia leading to acute lung injury modified the prognosis of trauma patients.
Intrapatient Reproducibility of the BISxp® Monitor
Authors: Niedhart Dagmar J. , Kaiser Heiko A. , Jacobsohn Eric , Hantler Charles B. , Evers Alex S. , Avidan Michael S. 
Published: January 2006

Background
The Bispectral Index (BIS) reportedly reflects anesthetic depth. It is recommended that anesthetic agents should be titrated to maintain the BIS between 40 and 60 arbitrary BIS units during anesthesia. For anesthesia providers to follow this recommendation, the monitor should be predictably affected by different anesthetic agents and have good interpatient and intrapatient reproducibility. The authors hypothesized that when two BISxp devices (Aspect Medical Systems, Newton, MA) are placed concurrently on the same patient, their readings are concordant throughout the anesthetic period.

Methods
Simultaneous BIS recordings from two BISxp monitors were obtained during anesthesia at 5-s intervals from 12 participants.

Results
In total 22,860 concurrent paired BIS readings were obtained. For 10.7% of the time, there were sustained periods of 30 s or greater where the readings suggested a different depth of anesthesia. For 6% of the time, there were sustained periods of 30 s or greater where the readings differed by 10 or more arbitrary BIS units. The regression coefficient (R) for the two devices was 0.65 (range, 0.35-0.92). There was zero bias between the devices, and the 95% limits of agreement ranged between -18 and +17.

Conclusion
A conflicting anesthetic management was suggested by the simultaneous BIS readings 10.7% of the time. These results suggest that BISxp does not always provide a reproducible single number. Anesthesia providers should not rely exclusively on the BIS reading when assessing depth of anesthesia.
Comparative Effects of Vaporized Perfluorohexane and Partial Liquid Ventilation in Oleic Acid– induced Lung Injury
Authors: de Abreu Marcelo Gama , Quelhas André Domingues , Spieth Peter , Bräuer Götz , Knels Lilla , Kasper Michael , Pino Alexandre Visintainer , Bleyl Jörg-Uwe , Hübler Matthias , Bozza Fernando , Salluh Jorge , Kuhlisch Eberhard , Giannella-Neto Antonio , Koch Thea 
Published: January 2006

Background
It is currently not known whether vaporized perfluorohexane is superior to partial liquid ventilation (PLV) for therapy of acute lung injury. In this study, the authors compared the effects of both therapies in oleic acid-induced lung injury.

Methods
Lung injury was induced in 30 anesthetized and mechanically ventilated pigs by means of central venous infusion of oleic acid. Animals were assigned to one of the following groups: (1) control or gas ventilation (GV), (2) 2.5% perfluorohexane vapor, (3) 5% perfluorohexane vapor, (4) 10% perfluorohexane vapor, or (5) PLV with perfluorooctane (30 ml/kg). Two hours after randomization, lungs were recruited and positive end-expiratory pressure was adjusted to obtain minimal elastance. Ventilation was continued during 4 additional hours, when animals were killed for lung histologic examination.

Results
Gas exchange and elastance were comparable among vaporized perfluorohexane, PLV, and GV before the open lung approach was used and improved in a similar fashion in all groups after positive end-expiratory pressure was adjusted to optimal elastance (P < 0.05). A similar behavior was observed in functional residual capacity (FRC) in animals treated with vaporized perfluorohexane and GV. Lung resistance improved after recruitment (P < 0.05), but values were higher in the 10% perfluorohexane and PLV groups as compared with GV (P < 0.05). Interestingly, positive end-expiratory pressure values required to obtain minimal elastance were lower with 5% perfluorohexane than with PLV and GV (P < 0.05). In addition, diffuse alveolar damage was significantly lower in the 5% and 10% perfluorohexane vapor groups as compared with PLV and GV (P < 0.05).

Conclusions
Although the use of 5% vaporized perfluorohexane permitted the authors to reduce pressures needed to stabilize the lungs and was associated with better histologic findings than were PLV and GV, none of these perfluorocarbon therapies improved gas exchange or lung mechanics as compared with GV.
Sonographic Visualization and Ultrasound-guided Block of the Third Occipital Nerve
Authors: Eichenberger Urs , Greher Manfred , Kapral Stephan , Marhofer Peter , Wiest Roland , Remonda Luca , Bogduk Nikolai , Curatolo Michele 
Published: January 2006

Background
Chronic neck pain after whiplash injury is caused by cervical zygapophysial joints in 50% of patients. Diagnostic blocks of nerves supplying the joints are performed using fluoroscopy. The authors' hypothesis was that the third occipital nerve can be visualized and blocked with use of an ultrasound-guided technique.

Methods
In 14 volunteers, the authors placed a needle ultrasound-guided to the third occipital nerve on both sides of the neck. They punctured caudal and perpendicular to the 14-MHz transducer. In 11 volunteers, 0.9 ml of either local anesthetic or normal saline was applied in a randomized, double-blind, crossover manner. Anesthesia was controlled in the corresponding skin area by pinprick and cold testing. The position of the needle was controlled by fluoroscopy.

Results
The third occipital nerve could be visualized in all subjects and showed a median diameter of 2.0 mm. Anesthesia was missing after local anesthetic in only one case. There was neither anesthesia nor hyposensitivity after any of the saline injections. The C2-C3 joint, in a transversal plane visualized as a convex density, was identified correctly by ultrasound in 27 of 28 cases, and 23 needles were placed correctly into the target zone.

Conclusions
The third occipital nerve can be visualized and blocked with use of an ultrasound-guided technique. The needles were positioned accurately in 82% of cases as confirmed by fluoroscopy; the nerve was blocked in 90% of cases. Because ultrasound is the only available technique today to visualize this nerve, it seems to be a promising new method for block guidance instead of fluoroscopy.
Ultrasound Examination and Localization of the Sciatic Nerve
Authors: Chan Vincent W. S. , Nova Hugo , Abbas Sherif , McCartney Colin J. L. , Perlas Anahi , Quan Xu Da 
Published: January 2006

Background
Few studies have examined the use of ultrasound for sciatic nerve localization. The authors evaluated the usefulness of low-frequency ultrasound in identifying the sciatic nerve at three locations in the lower extremity and in guiding needle advancement to target before nerve stimulation.

Methods
In this prospective observational study, 15 volunteers underwent sciatic nerve examination using a curved ultrasound probe in the range of 2-5 MHz and a Philips-ATL 5000 unit (ATL Ultrasound, Bothell, WA) in the gluteal, infragluteal, and proximal thigh regions. Thereafter, an insulated block needle was advanced inline with the ultrasound beam to reach the nerve target, which was further confirmed by electrical stimulation. The quality of sciatic nerve images, ease of needle to nerve contact, threshold stimulating current, and resultant motor response were recorded.

Results
The sciatic nerve was successfully identified in the transverse view as a solitary predominantly hyperechoic structure on ultrasound in all of the three regions examined. The target nerve was visualized easily in 87% and localized within two needle attempts in all patients. Nerve stimulation was successful in 100% after two attempts with a threshold current of 0.42 +/- 0.12 (mean +/- SD) eliciting foot plantarflexion or dorsiflexion.

Conclusions
These preliminary data show that a curved 2- to 5-MHz ultrasound probe provides good quality sciatic nerve imaging in the gluteal, infragluteal, and proximal thigh locations. Ultrasound-assisted sciatic nerve localization is potentially valuable for clinical sciatic nerve blocks.
Reduction of Verbal Pain Scores after Anterior Cruciate Ligament Reconstruction with 2-Day Continuous Femoral Nerve Block
Authors: Williams Brian A. , Kentor Michael L. , Vogt Molly T. , Irrgang James J. , Bottegal Matthew T. , West Robin V. , Harner Christopher D. , Fu Freddie H. , Williams John P. 
Published: January 2006

Background
Single-injection femoral nerve block analgesia and spinal anesthesia have been associated with fewer postoperative nursing interventions and successful same-day discharge after anterior cruciate ligament reconstruction. In the current study, the authors prospectively determined the effect of continuous femoral nerve block on a numeric rating scale (NRS) of pain intensity with movement for 7 postoperative days.

Methods
Patients undergoing this surgery with no history of previous invasive surgery on the same knee were recruited for this study. After standardized spinal anesthesia, intravenous sedation, and perioperative multimodal analgesia, patients received a femoral nerve catheter with (1) saline bolus (30 ml) plus saline infusion (270 ml at 5 ml/h, placebo group); (2) levobupivacaine (0.25%) bolus with saline infusion (group I), or (3) levobupivacaine (0.25%) bolus and infusion (group II). Patients were surveyed preoperatively and on postoperative days 1-4 and 7 to determine NRS scores (scale 0-10).

Results
Data from 233 participants were analyzed. On days 1-2, 50% of placebo patients had NRS scores of 5 or above, whereas among group II patients, only 25% had scores of 5 or above (P < 0.001). In regression models for NRS scores during days 1-4, group II was the only factor predicting lower pain scores (odds ratios, 0.3-0.5; P = 0.001-0.03). Overall, patients with preoperative NRS scores greater than 2 were likely to report higher NRS scores during days 1-7 (odds ratios, 3.3-5.2; P < 0.001).

Conclusions
Femoral nerve block catheters reliably keep NRS scores below the moderate-to-severe pain threshold for the first 4 days after anterior cruciate ligament reconstruction.