bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2X receptor characterization and IL‐1/IL‐1Ra release from human endothelial cells
Authors: Wilson H L , Varcoe R W , Stokes L , Holland K L , Francis S E , Dower S K , Surprenant A , Crossman D C 
Published: March 2007

Background and purpose:The pro‐inflammatory cytokine, interleukin‐1β (IL‐1β), has been implicated in the pathogenesis of atherosclerosis, potentially via its release from vascular endothelium. Endothelial cells (EC) synthesize IL‐1β in response to inflammatory stimuli, but the demonstration and mechanism of release of IL‐1 from ECs remains unclear. In activated monocytes, efficient release of bioactive IL‐1β occurred via activation of ATP‐gated P2X7 receptors (P2X7Rs). Activation of P2X7R in ECs from human umbilical vein (HUVECs) released IL‐1 receptor antagonist (IL‐1Ra). The purpose of this study was to provide a quantitative investigation of P2XR expression and function, in parallel with IL‐1β and IL‐1Ra synthesis, processing and release, in HUVECs under pro‐inflammatory conditions.Experimental approach:Quantitative RT‐PCR, immunoblotting, ELISA, flow cytometry, and whole‐cell patch clamp recordings were used to determine protein expression and receptor function. IL‐8‐luciferase‐reporter was used as an IL‐1 sensitive bioassay.Key results:HUVECs expressed P2X4R and P2X7R subtypes and both were significantly up‐regulated under inflammatory conditions. P2X7R currents were increased 3‐fold by inflammatory stimuli, whereas no P2X4R‐mediated currents were detected. Caspase‐1, but not IL‐1β, was present intracellularly under basal conditions; inflammatory stimuli activated the synthesis of intracellular pro‐IL‐1β and increased caspase‐1 levels. Activation of P2X7Rs resulted in low‐level release of bioactive IL‐1β and simultaneous release of IL‐1Ra. The net biological effect of release was anti‐inflammatory.Conclusions and implications:Endothelial P2X7Rs induced secretion of both pro‐ and anti‐inflammatory IL‐1 receptor ligands, the balance of which may provide a means for altering the inflammatory state of the arterial vessel wall.British Journal of Pharmacology (2007) 151, 96–108. doi:10.1038/sj.bjp.0707213
A new class of nitric oxide‐releasing derivatives of cetirizine; pharmacological profile in vascular and airway smooth muscle preparations
Authors: Larsson A‐K , Fumagalli F , DiGennaro A , Andersson M , Lundberg J , Edenius C , Govoni M , Monopoli A , Sala A , Dahlén S‐E , Folco G C 
Published: March 2007

Background and purpose:The pharmacological properties of compounds NCX 1512 and NCX 1514, synthesized by linking the histamine H1‐receptor antagonist cetirizine to NO‐releasing spacer groups, are reported. The aim was to establish if the compounds retained the antihistamine action of the parent compound, to assess their efficacy as NO donors and to test if they had broader antiallergic activity than cetirizine in the lung.Experimental approach:Antihistamine activity of NCX 1512 and NCX 1514 was investigated in vitro in the guinea pig ileum, in tracheal rings (GPTR) and lung parenchymal strips (GPLP) of the guinea‐pig. The NO‐releasing capacity was investigated in vascular preparations; the isolated rabbit and guinea‐pig aorta and guinea‐pig pulmonary artery. Kinetics of NO release were assessed in a rat whole blood assay.Key results:Both NCX 1512 and NCX 1514 retained activity as H1‐receptor antagonists in the guinea pig ileum and airway preparations. The NO‐releasing NCX compounds relaxed the rabbit aorta, an action prevented by the guanylyl cyclase inhibitor ODQ (10 μM). NCX 1512 and NCX 1514 did not relax the antigen (ovalbumin) pre‐contracted GPTR, whereas the NO donors NCX 2057 and DEA‐NONOate relaxed guinea‐pig pre‐contracted vascular and tracheal preparations. Cetirizine (1–100 μM) and NCX 1512 (1–100 μM) reduced the cumulative (0.01–100 μg ml−1) ovalbumin‐induced constriction in GPTR, but had no significant effect in GPLP.Conclusions and implications:NCX 1512 and NCX 1514 act as antihistamines and NO donors. However, there was no improved effect compared to cetirizine on antigen‐induced constriction of the central and peripheral lung.British Journal of Pharmacology (2007) 151, 35–44. doi:10.1038/sj.bjp.0707214
Synergistic vascular protective effects of combined low doses of PPARα and PPARγ activators in angiotensin II‐induced hypertension in rats
Authors: De Ciuceis C , Amiri F , Iglarz M , Cohn J S , Touyz R M , Schiffrin E L 
Published: March 2007

Background and Purpose:Protective cardiovascular effects of peroxisome proliferator activated receptor (PPAR)α and PPARγ activators have been demonstrated. If used as vasoprotective agents in high risk vascular patients rather than for their metabolic benefits, these agents could be associated with unwanted side effects. As a proof of concept to support the use of combined low doses of PPARα and PPARγ as vascular protective agents in high risk vascular patients, we tested the hypothesis that combined low doses of PPARα (fenofibrate) and PPARγ (rosiglitazone) activators would provide vascular protective benefits similar to full individual doses of these PPAR agonists.Experimental Approach:Male Sprague‐Dawley rats infused with Ang II (120 ng kg−1 min−1) were treated with rosiglitazone (1 or 2 mg kg−1 day−1) alone or concomitantly with fenofibrate (30 mg kg−1 day−1) for 7 days. Thereafter, vessels was assessed on a pressurized myograph, while NAD(P)H oxidase activity was determined by lucigenin chemiluminescence. Inflammation was evaluated using ELISA for NFκB and Western blotting for adhesion molecules.Key Results:Ang II‐induced blood pressure increase, impaired acetylcholine‐induced vasorelaxation, altered vascular structure, and enhanced vascular NAD(P)H oxidase activity and inflammation were significantly reduced by low dose rosiglitazone+fenofibrate.Conclusions and Implications:Combined low doses of PPARα and PPARγ activators attenuated development of hypertension, corrected vascular structural abnormalities, improved endothelial function, oxidative stress, and vascular inflammation. These agents used in low‐dose combination have synergistic vascular protective effects. The clinical effects of combined low‐dose PPARα and PPARγ activators as vascular protective therapy, potentially with reduced side‐effects and drug interactions, should be assessed.British Journal of Pharmacology (2007) 151, 45–53. doi:10.1038/sj.bjp.0707215
Endothelin‐1 activates ETAreceptors to cause reflex scratching in BALB/c mice
Authors: McQueen D S , Noble M A H , Bond S M 
Published: March 2007

Background and purpose:Endothelin‐1 (ET‐1) is present in murine and human skin and causes itch (pruritus) when injected in humans. This behavioural study examined the scratch reflex evoked by ET‐1 in mice.Experimental approach:An automated detector was used to determine whether ET‐1 causes reflex scratching, the behavioural correlate of itching, in BALB/c mice. Selective agonists and antagonists were used to probe the ET receptor(s) involved.Key results:ET‐1 evoked dose‐related reflex scratching lasting up to 20 min following intradermal injection (0.1‐100 ng; 0.04‐40 pmol). The ED50for ET‐1 induced scratching was 2.1 ng and desensitization occurred with cumulative dosing. High doses of the ETBreceptor agonist IRL1620 (10 μg; 5.5 nmol), also caused scratching (ED501.3μg, 0.7 nmol). The ETAreceptor antagonist BQ123 significantly reduced scratching evoked by ET‐1 and IRL 1620, suggesting that both agonists caused scratching via an ETAreceptor‐dependent mechanism. The ETBreceptor antagonist BQ788 significantly reduced scratching evoked by IRL1620 but had no effect on scratching evoked by ET‐1. This indicated that activation of ETBreceptors by high doses of ETBagonist, but not ET‐1, can trigger scratching.Conclusion and implications:ET‐1 is a potent endogenous activator of reflex scratching (itch). Mechanisms for ET‐induced scratching are considered, including direct action of ET‐1 on pruriceptive nerve endings and indirect actions via release of endogenous mediators such as histamine from mast cells. ET‐1 and ETAreceptors, possibly also ETBreceptors, are potential targets for developing specific anti‐pruritic drugs to treat pruritic skin disorders such as atopic dermatitis.British Journal of Pharmacology(2007)151, 278–284. doi:10.1038/sj.bjp.0707216
Metabotropic P2Y receptors inhibit P2X3receptor‐channels via G protein‐dependent facilitation of their desensitization
Authors: Gerevich Z , Zadori Z , Müller C , Wirkner K , Schröder W , Rubini P , Illes P 
Published: March 2007

Background and purpose:The aim of the present study was to investigate whether the endogenous metabotropic P2Y receptors modulate ionotropic P2X3receptor‐channels.Experimental approach:Whole‐cell patch‐clamp experiments were carried out on HEK293 cells permanently transfected with human P2X3receptors (HEK293‐hP2X3cells) and rat dorsal root ganglion (DRG) neurons.Key results:In both cell types, the P2Y1,12,13receptor agonist, ADP‐β‐S, inhibited P2X3currents evoked by the selective agonist, α,β‐methylene ATP (α,β‐meATP). This inhibition could be markedly counteracted by replacing in the pipette solution the usual GTP with GDP‐β‐S, a procedure known to block all G protein heterotrimers. P2X3currents evoked by ATP, activating both P2Y and P2X receptors, caused a smaller peak amplitude and desensitized faster than those currents evoked by the selective P2X3receptor agonist α,β‐meATP. In the presence of intracellular GDP‐β‐S, ATP‐ and α,β‐meATP‐induced currents were identical. Recovery from P2X3receptor desensitization induced by repetitive ATP application was slower than the recovery from α,β‐meATP‐induced desensitization. When G proteins were blocked by intracellular GDP‐β‐S, the recovery from the ATP‐ and α,β‐meATP‐induced desensitization were of comparable speed.Conclusions and Implications:Our results suggest that the activation of P2Y receptors G protein‐dependently facilitates the desensitization of P2X3receptors and suppresses the recovery from the desensitized state. Hence, the concomitant stimulation of P2X3and P2Y receptors of DRG neurons by ATP may result both in an algesic effect and a partly counterbalancing analgesic activity.British Journal of Pharmacology(2007)151, 226–236. doi:10.1038/sj.bjp.0707217
Methyl p‐hydroxybenzoate causes pain sensation through activation of TRPA1 channels
Authors: Fujita F , Moriyama T , Higashi T , Shima A , Tominaga M 
Published: March 2007

Background and purpose:Parabens are commonly added in pharmaceutical, cosmetic and food products because of their wide antibacterial properties, low toxicity, inertness and chemical stability, although the molecular mechanism of their antibacterial effect is not fully understood. Some agonists of the transient receptor potential (TRP) A1 channels are known to have strong antibacterial activities. Therefore, a series of experiments was conducted to find out the effects of parabens on TRP channels expressed in sensory neurons, particularly the TRPA1 channels.Experimental approach:Effects of parabens, especially of methyl p‐hydroxybenzoate (methyl paraben) on TRP channel activities were examined using Ca2+‐imaging and patch‐clamp methods. In addition, an involvement of methyl paraben in the development of pain‐related behavior in mice was investigated.Key results:Methyl paraben specifically activated TRPA1 in both HEK293 cells expressing TRPA1 and in mouse sensory neurons with an EC50 value of 4.4 mM, an attainable concentration in methyl paraben‐containing products. Methyl paraben caused pain‐related behavior in mice similar to that caused by allyl isothiocyanate, which was blocked by the TRP channel blocker, ruthenium red.Conclusions and implications:Our data indicate that methyl paraben is able to activate TRPA1 channels and can cause pain sensation. As such, methyl paraben provides a useful tool for investigating TRPA1 function and development of antinociceptive agents acting on TRPA1 channels.British Journal of Pharmacology (2007) 151, 134–141. doi:10.1038/sj.bjp.0707219
Intravenous Lidocaine Infusion Facilitates Acute Rehabilitation after Laparoscopic Colectomy
Authors: Kaba Abdourahamane , Laurent Stanislas R. , Detroz Bernard J. , Sessler Daniel I. , Durieux Marcel E. , Lamy Maurice L. , Joris Jean L. 
Published: March 2007

Background
Intravenous infusion of lidocaine decreases postoperative pain and speeds the return of bowel function. The authors therefore tested the hypothesis that perioperative lidocaine infusion facilitates acute rehabilitation protocol in patients undergoing laparoscopic colectomy.

Methods
Forty patients scheduled to undergo laparoscopic colectomy were randomly allocated to receive intravenous lidocaine (bolus injection of 1.5 mg/kg lidocaine at induction of anesthesia, then a continuous infusion of 2 mg.kg.h intraoperatively and 1.33 mg.kg.h for 24 h postoperatively) or an equal volume of saline. All patients received similar intensive postoperative rehabilitation. Postoperative pain scores, opioid consumption, and fatigue scores were measured. Times to first flatus, defecation, and hospital discharge were recorded. Postoperative endocrine (cortisol and catecholamines) and metabolic (leukocytes, C-reactive protein, and glucose) responses were measured for 48 h. Data (presented as median [25-75% interquartile range], lidocaine vs. saline groups) were analyzed using Mann-Whitney tests. P<0.05 was considered statistically significant.

Results
Patient demographics were similar in the two groups. Times to first flatus (17 [11-24] vs. 28 [25-33] h; P<0.001), defecation (28 [24-37] vs. 51 [41-70] h; P=0.001), and hospital discharge (2 [2-3] vs. 3 [3-4] days; P=0.001) were significantly shorter in patients who received lidocaine. Lidocaine significantly reduced opioid consumption (8 [5-18] vs. 22 [14-36] mg; P=0.005) and postoperative pain and fatigue scores. In contrast, endocrine and metabolic responses were similar in the two groups.

Conclusions
Intravenous lidocaine improves postoperative analgesia, fatigue, and bowel function after laparoscopic colectomy. These benefits are associated with a significant reduction in hospital stay.
Racial Differences in the Use of Epidural Analgesia for Labor
Authors: Glance Laurent G. , Wissler Richard . , Glantz Christopher , Osler Turner M. , Mukamel Dana B. , Dick Andrew W. 
Published: March 2007

Background
There is strong evidence that pain is undertreated in black and Hispanic patients. The association between race and ethnicity and the use of epidural analgesia for labor is not well described.

Methods
Using the New York State Perinatal Database, the authors examined whether race and ethnicity were associated with the likelihood of receiving epidural analgesia for labor after adjusting for clinical characteristics, demographics, insurance coverage, and provider effect. This retrospective cohort study was based on 81,883 women admitted for childbirth between 1998 and 2003.

Results
Overall, 38.3% of the patients received epidural analgesia for labor. After adjusting for clinical risk factors, socioeconomic status, and provider fixed effects, Hispanic and black patients were less likely than non-Hispanic white patients to receive epidural analgesia: The adjusted odds ratio was 0.85 (95% CI, 0.78-0.93) for white/Hispanic and 0.78 (0.74-0.83) for blacks compared with non-Hispanic whites. Compared with patients with private insurance, patients without insurance were least likely to receive epidural analgesia (adjusted odds ratio, 0.76; 95% CI, 0.64-0.89). Black patients with private insurance had similar rates of epidural use to white/non-Hispanic patients without insurance coverage: The adjusted odds ratio was 0.66 (95% CI, 0.53-0.82) for white/non-Hispanic patients without insurance versus 0.69 (0.57-0.85) for black patients with private insurance.

Conclusion
Black and Hispanic women in labor are less likely than non-Hispanic white women to receive epidural analgesia. These differences remain after accounting for differences in insurance coverage, provider practice, and clinical characteristics.
Late Psychological Symptoms after Awareness among Consecutively Included Surgical Patients
Authors: Samuelsson Peter , Brudin Lars , Sandin Rolf H. 
Published: March 2007

Background
Awareness during general anesthesia can cause late psychological symptoms. Selection bias may have affected the results in previous retrospective studies. The authors used prospective consecutive collection to recruit patients with previous awareness.

Methods
In a cohort of 2,681 consecutive patients scheduled to undergo general anesthesia, 98 considered themselves to have been aware during previous surgery. Six patients died before inclusion, and another 13 were excluded (4 cases of stroke or dementia, 7 declined to participate, and 2 could not be located). Seventy-nine patients were interviewed by telephone, and medical records were checked in uncertain cases. The interview followed a structured protocol, including seven late symptoms (anxiety, chronic fear, nightmares, flashbacks, indifference, loneliness, and lack of confidence in future life). Three persons independently assessed the interviews for classification, to determine whether awareness had occurred.

Results
Four cases were performed using regional anesthesia, and another 29 were not considered as awareness by the assessors. Therefore, the final analyses included 46 patients. Twenty (43%) had experienced pain, and 30 (65%) described acute emotional reactions during the awareness episode. Fifteen (33%) patients had experienced late psychological symptoms afterward. In 6 of those cases, the symptoms lasted for more than 2 months, and 1 patient had a diagnosis of post-traumatic stress disorder. Acute emotional reactions were significantly related to late psychological symptoms (P<0.05).

Conclusion
The method for recruiting awareness cases in studies on late psychological symptoms may affect the result. The authors found fewer and milder problems, despite a similar degree of initial problems as in previous studies.
Dreaming during Anesthesia and Anesthetic Depth in Elective Surgery Patients
Authors: Leslie Kate , Skrzypek Hannah , Paech Michael J. , Kurowski Irina , Whybrow Tracey 
Published: March 2007

Background
Dreaming reported after anesthesia remains a poorly understood phenomenon. Dreaming may be related to light anesthesia and represent near-miss awareness. However, few studies have assessed the relation between dreaming and depth of anesthesia, and their results were inconclusive. Therefore, the authors tested the hypothesis that dreaming during anesthesia is associated with light anesthesia, as evidenced by higher Bispectral Index values during maintenance of anesthesia.

Methods
With approval, 300 consenting healthy patients, aged 18-50 yr, presenting for elective surgery requiring relaxant general anesthesia with a broad range of agents were studied. Patients were interviewed on emergence and 2-4 h postoperatively. The Bispectral Index was recorded from induction until the first interview. Dream content and form were also assessed.

Results
Dreaming was reported by 22% of patients on emergence. There was no difference between dreamers and nondreamers in median Bispectral Index values during maintenance (37 [23-55] vs. 38 [20-59]; P=0.68) or the time at Bispectral Index values greater than 60 (0 [0-7] vs. 0 [0-31] min; P=0.38). Dreamers tended to be younger and male, to have high home dream recall, to receive propofol maintenance or regional anesthesia, and to open their eyes sooner after surgery. Most dreams were similar to dreams of sleep and were pleasant, and the content was unrelated to surgery.

Conclusions
Dreaming during anesthesia is unrelated to the depth of anesthesia in almost all cases. Similarities with dreams of sleep suggest that anesthetic dreaming occurs during recovery, when patients are sedated or in a physiologic sleep state.
Pharmacokinetics of Ropivacaine in Patients with Chronic End-stage Liver Disease
Authors: Jokinen Mika J. , Neuvonen Pertti J. , Lindgren Leena , Höckerstedt Krister , Sjövall Jan , Breuer Olof , Askemark Yvonne , Ahonen Jouni , Olkkola Klaus T. 
Published: March 2007

Background
Ropivacaine is mainly eliminated by hepatic metabolism. The authors studied the effect of chronic end-stage liver disease on the pharmacokinetics of ropivacaine.

Methods
Thirteen patients with chronic end-stage liver disease and eight healthy volunteers received a single dose of 0.6 mg/kg ropivacaine intravenously over 30 min. Ropivacaine, 3-hydroxyropivacaine, and 2',6'-pipecoloxylidide were measured in venous plasma and urine.

Results
Peak ropivacaine plasma concentrations were similar. Patients with chronic end-stage liver disease had, on average, 60% lower total (P=0.001) and 56% lower unbound plasma clearance (P=0.002), 59% higher steady state volume of distribution (P=0.03), and 4.2-fold longer half-life (P<0.001) of ropivacaine. Of the variation in total ropivacaine clearance, 69% was accounted for by variation in albumin, 57% in prealbumin, 25% in international normalized ratio of plasma thromboplastin time, and 24% in galactose half-life. The patients excreted a larger fraction of the original dose as unchanged ropivacaine (2.1% vs. 0.3%; P<0.001) and a smaller fraction as 3-hydroxyropivacaine (11% vs. 27%; P=0.001). The fraction excreted as 2',6'-pipecoloxylidide (4.7% vs. 5.0%) was similar.

Conclusions
Ropivacaine clearance is decreased in chronic end-stage liver disease. A normal dose can be considered for a single block in patients with liver impairment, because the peak plasma concentrations were essentially similar. When using a postoperative ropivacaine infusion in a patient with end-stage liver disease, the lowest effective dose should be used for the shortest possible time and the patient should be monitored closely, because systemic toxicity cannot be ruled out. Because of wide interindividual differences in pharmacokinetics in patients with liver disease, no definitive dosing instructions can be given.
A Randomized Crossover Comparison of the Effects of Propofol and Sevoflurane on Cerebral Hemodynamics during Carotid Endarterectomy
Authors: McCulloch Timothy J. , Thompson Christopher L. , Turner Martin J. 
Published: March 2007

Background
Intravenous and inhalational anesthetic agents have differing effects on cerebral hemodynamics: Sevoflurane causes some vasodilation, whereas propofol does not. The authors hypothesized that these differences affect internal carotid artery pressure (ICAP) and the apparent zero flow pressure (critical closing pressure) during carotid endarterectomy. Vasodilation is expected to increase blood flow, reduce ICAP, and reduce apparent zero flow pressure.

Methods
In a randomized crossover study, the gradient between systemic arterial pressure and ICAP during carotid clamping was measured while changing between sevoflurane and propofol in 32 patients. Middle cerebral artery blood velocity, recorded by transcranial Doppler, and ICAP waveforms were analyzed to determine the apparent zero flow pressure.

Results
ICAP increased when changing from sevoflurane to propofol, causing the mean gradient between arterial pressure and ICAP to decrease by 10 mmHg (95% confidence interval, 6-14 mmHg; P<0.0001). Changing from propofol to sevoflurane had the opposite effect: The pressure gradient increased by 5 mmHg (95% confidence interval, 2-7 mmHg; P=0.002). Ipsilateral middle cerebral artery blood velocity decreased when changing from sevoflurane to propofol. Cerebral steal was detected in one patient after changing from propofol to sevoflurane. The apparent zero flow pressure (mean+/-SD) was 22+/-10 mmHg with sevoflurane and 30+/-14 mmHg with propofol (P<0.01). There was incomplete drug crossover due to the limited duration of carotid clamping.

Conclusions
Compared with sevoflurane, ipsilateral ICAP and apparent zero flow pressure are both higher with propofol. Vasodilatation associated with sevoflurane can cause cerebral steal.