bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostaglandin E2 activates EP2 receptors to inhibit human lung mast cell degranulation
Authors: Kay Linda J , Yeo Wilfred W , Peachell Peter T 
Published: January 2006

The prostanoid, PGE2, is known to inhibit human lung mast cell activity. The aim of the present study was to characterize the EP receptor that mediates this effect.
PGE2 (pEC50, 5.8±0.1) inhibited the IgE‐mediated release of histamine from mast cells in a concentration‐dependent manner. Alternative EP receptor agonists were studied. The EP2‐selective agonist, butaprost (pEC50, 5.2±0.2), was an effective inhibitor of mediator release whereas the EP1/EP3 receptor agonist, sulprostone, and the EP1‐selective agonist, 17‐phenyl‐trinor‐PGE2, were ineffective.
The DP agonist PGD2, the FP agonist PGF2α, the IP agonist iloprost and the TP agonist U‐46619 were ineffective inhibitors of IgE‐mediated histamine release from mast cells.
PGE2 induced a concentration‐dependent increase in intracellular cAMP levels in mast cells.
The effects of the EP1/EP2 receptor antagonist, AH6809, and the EP4 receptor antagonist, AH23848, on the PGE2‐mediated inhibition of histamine release were determined. AH6809 (pKB, 5.6±0.1) caused a modest rightward shift in the PGE2 concentration–response curve, whereas AH23848 was ineffective.
Long‐term (24 h) incubation of mast cells with either PGE2 or butaprost (EP2 agonist), but not sulprostone (EP1/EP3 agonist), caused a significant reduction in the subsequent ability of PGE2 to inhibit histamine release.
Collectively, these data suggest that PGE2 mediates effects on human lung mast cells by interacting with EP2 receptors.

British Journal of Pharmacology (2006) 147, 707–713. doi:10.1038/sj.bjp.0706664
Systemic administration of β2‐adrenoceptor agonists, formoterol and salmeterol, elicit skeletal muscle hypertrophy in rats at micromolar doses
Authors: Ryall James G , Sillence Martin N , Lynch Gordon S 
Published: January 2006

β2‐Adrenoceptor agonists provide a potential therapy for muscle wasting and weakness, but their use may be limited by adverse effects on the heart, mediated in part, by β1‐adrenoceptor activation.
Two β2‐agonists, formoterol and salmeterol, are approved for treating asthma and have an extended duration of action and increased safety, associated with greater β2‐adrenoceptor selectivity.
The pharmacological profiles of formoterol and salmeterol and their effects on skeletal and cardiac muscle mass were investigated in 12‐week‐old, male F344 rats. Formoterol and salmeterol were each administered via daily i.p. injection at one of seven doses (ranging from 1 to 2000 μg kg−1 day−1), for 4 weeks. Rats were anaesthetised and the EDL and soleus muscles and the heart were excised and weighed. Dose–response curves were constructed based on skeletal and cardiac muscle hypertrophy.
Formoterol was more potent than salmeterol, with a significantly lower ED50 in EDL muscles (1 and 130 μg kg−1 day−1, P <0.05), whereas salmeterol had greater intrinsic activity than formoterol in both EDL and soleus muscles (12% greater hypertrophy than formoterol). The drugs had similar potency and intrinsic activity in the heart, with a smaller leftward shift for formoterol than seen in skeletal muscle. A dose of 25 μg kg−1 day−1 of formoterol elicited greater EDL and soleus hypertrophy than salmeterol, but resulted in similar β‐adrenoceptor downregulation.
These results show that doses as low as 1 μg kg−1 day−1 of formoterol can elicit significant muscle hypertrophy with minimal cardiac hypertrophy and provide important information regarding the potential therapeutic use of formoterol and salmeterol for muscle wasting.

British Journal of Pharmacology (2006) 147, 587–595. doi:10.1038/sj.bjp.0706669
Cardiac implications for the use ofβ2‐adrenoceptor agonists for the management of muscle wasting
Authors: Molenaar Peter , Chen Lu , Parsonage William A 
Published: January 2006

There are proposals for the implementation ofβ2‐adrenoceptor agonists for the management of muscle wasting diseases. The idea has been initiated by studies in animal models which show thatβ2‐adrenoceptor agonists cause hypertrophy of skeletal muscle. Their use in clinical practice will also need an understanding of possible effects of activation of human heartβ2‐adrenoceptors. Consequences could include an increased probability of arrhythmias in susceptible patients.British Journal of Pharmacology(2006)147, 583–586. doi:10.1038/sj.bjp.0706670
Inhibition of classical PKC isoenzymes downregulates STAT1 activation and iNOS expression in LPS‐treated murine J774 macrophages
Authors: Salonen Tiina , Sareila Outi , Jalonen Ulla , Kankaanranta Hannu , Tuominen Raimo , Moilanen Eeva 
Published: January 2006

Proinflammatory cytokines and bacterial products trigger inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in inflammatory and tissue cells. In inflammation, NO acts as an important mediator having both proinflammatory and destructive effects.
Protein kinase C (PKC) is a family of serine–threonine protein kinase isoenzymes involved in signal transduction pathways related to inflammatory responses. The aim of the present study was to investigate the role of classical PKC (cPKC) isoenzymes in the regulation of iNOS expression and NO production in murine J774 macrophages and the mechanisms involved.
RO318220 (inhibits PKCβ, PKCγ and PKCɛ), GÖ6976 (inhibits cPKC isoenzymes PKCα and PKCβ) and LY333531 (inhibits PKCβ) reduced lipopolysaccharide (LPS)‐induced NO production and iNOS expression in a dose‐dependent manner as did 6 h pretreatment with 1 μM phorbol 12‐myristate 13‐acetate (PMA) (which was shown to downregulate PKC expression).
PKC inhibitors also reduced LPS‐induced iNOS mRNA levels, but they did not affect the half‐life of iNOS mRNA. PKC inhibitors did not alter LPS‐induced activation of NF‐κB as measured by electrophoretic mobility shift assay.
All PKC inhibitors used and pretreatment with 1 μM PMA inhibited signal transducer and activator of transcription 1 (STAT1) activation as measured by the translocation of STAT1α from the cytosol to the nucleus by Western blot. In addition, inhibition of STAT1 activation by AG‐490, an inhibitor of JAK‐2, also reduced NO production.
These results suggest that cPKC isoenzymes, especially PKCβ, mediate the upregulation of iNOS expression and NO production in activated macrophages in an NF‐κB‐independent manner, possibly through the activation of transcription factor STAT1.

British Journal of Pharmacology (2006) 147, 790–799. doi:10.1038/sj.bjp.0706672
Lightwand Tracheal Intubation with and without Muscle Relaxation
Authors: Massó Eva , Sabaté Sergi , Hinojosa Marta , Vila Pere , Canet Jaume , Langeron Olivier 
Published: January 2006

Background
Lightwand tracheal intubation is a suitable technique for patients who are difficult to intubate but who are receiving effective ventilation. The effect of muscle relaxants on the efficacy of lightwand intubation has not yet been evaluated. The authors conducted a prospective, double-blind, placebo-controlled study to assess the effectiveness and incidence of complications of lightwand tracheal intubation performed during general anesthesia with and without the use of a muscle relaxant in patients with apparently normal airway anatomy.

Methods
One hundred seventy-six patients who required orotracheal intubation were prospectively included. Anesthesia was administered using propofol (2 mg/kg, then 3 mg . kg (-1). h(-1)) and remifentanil (1 microg/kg, then 0.3 microg . kg(-1) . min(-1)). Patients were randomly assigned to one of two groups (n = 88 for each) to receive rocuronium 0.6 mg/kg or saline intravenously. Lightwand orotracheal intubation (Trachlight; Laerdal Medical Inc., Armonk, NY) was attempted after 3 min. The authors recorded the number of successful intubations, the number of attempts and their duration, and events during the procedure.

Results
The failure rate of lightwand intubation was 12% in the placebo group and 2% in the rocuronium group (P = 0.021). Patients in the placebo group received more multiple intubation attempts (P < 0.001), required a greater intubation time (77 +/- 65 vs. 52 +/- 31 s; P = 0.002) and experienced a greater incidence of events during intubation (61 vs. 0%; P < 0.001) than patients in the rocuronium group.

Conclusions
The use of muscle relaxants in patients with apparently normal airways is associated with a lower failure rate, decreased intubation time, and fewer attempts when performing lightwand orotracheal intubation.
Devices for Lung Isolation Used by Anesthesiologists with Limited Thoracic Experience
Authors: Campos Javier H. , Hallam Ezra A. , Van Natta Timothy , Kernstine Kemp H. 
Published: January 2006

Background
Lung isolation is accomplished with a double-lumen tube or a bronchial blocker. Previous studies comparing lung isolation methods were performed by experienced anesthesiologists in thoracic anesthesia. Therefore, the results of these studies may not be relevant to the anesthesiologist with limited experience. This study compared the success rates of lung isolation devices among anesthesiologists with limited experience in thoracic anesthesia.

Methods
A prospective, randomized trial was designed to determine the success and time required for proper placement of the left-sided double-lumen tube (n = 22), the Univent tube (Vitaid Ltd., Lewiston, NY; n = 22), and the Arndt Blocker (Cook Critical Care, Bloomington, IN; n = 22). Anesthesiologists with less than two lung isolation cases per month were included (faculty n = 17 and senior residents n = 11). Variables recorded included (1) successful placement (as determined by an independent observer), (2) time of placement, and (3) the number of times the fiberoptic bronchoscope was used.

Results
Participants failed to place or position their assigned device in 25 of 66 patients (failure was 39% among faculty and 36% among senior residents). The failure rate did not differ among the three devices (P = 0.65). The median (25th-75th percentile) times to complete the placement procedures were as follows: (1) double-lumen tube: 6.1 min (4.6-9.5 min), (2) Univent tube: 6.7 min (4.9-8.8 min), and (3) Arndt Blocker: 8.6 min (5.8-17.5 min) (P = 0.45 comparing all devices). After device malposition was identified, it took 1 min or less for the investigating anesthesiologist to achieve optimal position.

Conclusions
Anesthesiologists with limited experience in thoracic anesthesia frequently fail to successfully place lung isolation devices. Rapid successful device placement by an experienced anesthesiologist excluded any contribution of uniquely difficult anatomy. The nature of the malpositions suggests that the most critical factor in successful placement was the anesthesiologist's knowledge of endoscopic bronchial anatomy.
Impact of Postoperative Unwashed Shed Blood Retrieved after Total Knee Arthroplasty on Endotoxin-stimulated Tumor Necrosis Factor α Release In Vitro
Authors: Muñoz Manuel , Muñoz Encarnación , Navajas Ana , Campos Arturo , Rius Francisca , Gómez Aurelio 
Published: January 2006

Background
: Allogeneic or autologous blood seems to have an immunosuppressive effect that is largely attributable to storage-dependent factors. However, transfusion of postoperative unwashed shed blood (USB) after elective total knee replacement does not undergo storage. Therefore, the authors explored the effects of USB on the mitogen-driven cytokine synthesis by the patient's peripheral blood mononuclear cells.

Methods
: Perioperative blood samples were obtained from 12 total knee replacement patients with and 5 without reinfusion of leukoreduced USB, and from USB reinfusion line, before and after leukoreduction. Venous blood obtained at 4-6 postoperative hours was coincubated with USB. Endotoxin-stimulated release of tumor necrosis factor alpha and interleukin 10 was measured after 24 h of culture by solid-phase enzyme-labeled chemiluminescent immunometric assay.

Results
: Coincubation of postoperative venous blood with USB, USB cells, or USB plasma resulted in a significant depression of tumor necrosis factor-alpha synthesis, without significant effects on interleukin-10 synthesis. However, no differences were observed for endotoxin-stimulated cytokine release in perioperative blood samples from patients receiving or not receiving USB.

Conclusion
: These data suggest that USB seemed to contain an antiinflammatory agent. However, at the actual retransfusion rate, USB does not seem to further enhance the immunosuppression that follows knee replacement surgery.
Cerebral Blood Flow Affects Dose Requirements of Intracarotid Propofol for Electrocerebral Silence
Authors: Joshi Shailendra , Wang Mei , Etu Joshua J. , Nishanian Ervant V. , Pile-Spellman John 
Published: January 2006

Background
The authors hypothesized that cerebral blood flow (CBF) changes will affect the dose of intracarotid propofol required to produce electrocerebral silence.

Methods
The authors tested their hypothesis on New Zealand White rabbits. The first group of 9 animals received intracarotid propofol during (1) normoventilation, (2) hyperventilation, and (3) hypoventilation. The second group of 14 animals received intracarotid propofol with or without concurrent intraarterial verapamil, a potent cerebral vasodilator. The third group of 8 animals received bolus injection of propofol during normotension, during severe cerebral hypoperfusion, and after hemodynamic recovery.

Results
In the first group, there was a linear correlation between the dose of intracarotid propofol and percent change (%Delta) in CBF from the baseline due to changes in the minute ventilation, Total Dose (y) = 0.17 + 0.012 * %Delta CBF (x), n = 27, r = 0.76. In the second group, the dose of propofol was also a function of CBF change after verapamil, Total Dose (y) = 0.98 + 0.1 * %Delta CBF (x), n = 14, r = 0.75. In the third group, the duration of electrocerebral silence after intracarotid propofol (3 mg) was significantly increased with concurrent cerebral hypoperfusion compared with prehypoperfusion and posthypoperfusion values (141 +/- 38 vs. 19 +/- 24 and 16 +/- 12 s, respectively, P < 0.0001).

Conclusions
The authors conclude that CBF affects the dose requirements of intracarotid propofol required to produce electrocerebral silence. Furthermore, the manipulation of CBF might be a useful tool to enhance the efficacy of intracarotid drugs.
Age-dependent Responses to Nerve Injury– induced Mechanical Allodynia
Authors: Ririe Douglas G. , Eisenach James C. 
Published: January 2006

Background
Developmental differences in responses to acute and chronic nerve injury have received minimal attention. This study examines developmental differences in behavioral responses to a proximal (closer to the spinal cord) (L5 and L6 spinal nerve root ligation) or to a more distal (closer to peripheral innervation) (partial sciatic nerve ligation) nerve injury in rats paralleling the infant to young adult human.

Methods
Withdrawal thresholds to von Frey filament testing in the hind paw were determined before and various times after either spinal nerve root ligation or partial sciatic nerve ligation in rats aged 2, 4, and 16 weeks. Control rats of these ages were observed serially without surgery. Times for withdrawal thresholds to mechanical stimuli to return to 80% of that of the hind paw in the control animals were compared among the different ages in the two models.

Results
Baseline withdrawal thresholds in younger rats were lower (P < 0.05). In the 2-week-old animals, distal injury partial sciatic nerve ligation did not cause a reduction in withdrawal threshold from baseline. This was different from the spinal nerve root ligation group and the older animals in the partial sciatic nerve ligation group. However, when compared with age-matched control animals, both nerve injuries resulted in reduced withdrawal thresholds (P < 0.05). The resolution of hypersensitivity to mechanical stimulation, as measured by return of threshold to 80% of controls, occurred more quickly in 2-week-old than in 4- and 16-week-old animals in both injury models (P < 0.05).

Conclusion
These data suggest that resolution of sensitization to A-fiber input occurs more rapidly in young animals. In addition, distal injury has less of a sensitizing effect on A-fiber input than proximal injury in the younger animals. The authors speculate that neuroimmune responses, especially at the site of injury, are developmentally regulated and less likely to produce chronic pain when injury occurs at a young age.
Population dynamics of a host‐specific root‐feeding cyst nematode and resource quantity in the root zone of a clonal grass
Authors: Van der Stoel C. D. , Duyts H. , Van der Putten W. H. 
Published: January 2006

Recent studies have suggested that root‐feeding nematodes influence plant community dynamics, but few studies have investigated the population dynamics of the nematodes. In coastal foredunes, feeding‐specialist cyst nematodes (Heterodera spp.) are dominant in the soil nematode community and greenhouse studies pointed at bottom‐up control by their host plant. Here we examine the population dynamics of H. arenaria in the field in relation to resource quantity in the root zone of Ammophila arenaria (marram grass). Ammophila arenaria is a pioneer grass in mobile coastal foredunes of northwestern and Mediterranean Europe. Every year, the plant expands clonally into freshly deposited layers of wind‐blown sand, followed by dispersal and build‐up of the nematode population into the new root zone. In a newly developing root zone the first H. arenaria cysts were observed one month after the first new roots were detected, indicating that nematode dispersal is not limiting the initial establishment of new populations. Throughout the growth season, the numbers of cysts, as well as the numbers of eggs and juveniles within cysts, were related to the quantity of roots. However, cyst density varied between years. Therefore, we conclude that in new root layers of A. arenaria cyst nematodes are bottom‐up controlled by resource quantity, but that other factors, for example resource quality, influence the relation between nematode abundance and resource quantity.In deeper root zones the nematode abundance declines over time. Here, numbers of cysts were not related to root biomass, while numbers of eggs and juveniles inside the cysts were weakly related. This points at other factors than resource quantity, for example the quality of the roots or unsuitable abiotic environmental conditions that have a stronger influence on cyst numbers than resource quantity. We discuss how bottom‐up control of cyst nematodes may indirectly protect the plant against harmful root knot nematodes.
Intraoral duct ligation without inclusion of the parasympathetic nerve supply induces rat submandibular gland atrophy
Authors: Osailan Samira M. , Proctor Gordon B. , McGurk Mark , Paterson Katherine L. 
Published: January 2006

SummaryThe atrophic effect of ligating the main duct of the right submandibular gland was examined in rat using a novel intraoral approach that did not include the chorda lingual (CL) nerve. Comparison was made with the effect of duct ligation including the attached CL nerve as carried out in previous studies. In all animals, the contralateral, unligated left submandibular gland was used as a control. At different times (1, 2, 7, 14 and 21 days) after ligation, glands were removed and weighed. Tissue was fixed for morphological analysis and homogenized for biochemical assay of secretory proteins. After 21 days, ligated glands showed a significant decrease in wet weight compared with unligated glands. Weight loss was the greatest (P < 0.05) in glands ligated with the CL nerve included. Light microscopy revealed that following ligation, an initial inflammatory reaction was followed by severe atrophy of acini and granular ducts. The atrophy was less severe when the CL nerve was not ligated. Secretory proteins were decreased from day 1 onwards following duct ligation in both groups. It can be concluded that most of the atrophy induced by duct ligation is independent of damage caused to the parasympathetic nerve supply, although the latter causes a greater atrophy presumably due to denervation.
Mouse models in non‐alcoholic fatty liver disease and steatohepatitis research
Authors: Anstee Quentin M. , Goldin Robert D. 
Published: January 2006

SummaryNon‐alcoholic fatty liver disease (NAFLD) represents a histological spectrum of liver disease associated with obesity, diabetes and insulin resistance that extends from isolated steatosis to steatohepatitis and cirrhosis. As well as being a potential cause of progressive liver disease in its own right, steatosis has been shown to be an important cofactor in the pathogenesis of many other liver diseases. Animal models of NAFLD may be divided into two broad categories: those caused by genetic mutation and those with an acquired phenotype produced by dietary or pharmacological manipulation. The literature contains numerous different mouse models that exhibit histological evidence of hepatic steatosis or, more variably, steatohepatitis; however, few replicate the entire human phenotype. The genetic leptin‐deficient (ob/ob) or leptin‐resistant (db/db) mouse and the dietary methionine/choline‐deficient model are used in the majority of published research. More recently, targeted gene disruption and the use of supra‐nutritional diets to induce NAFLD have gained greater prominence as researchers have attempted to bridge the phenotype gap between the available models and the human disease. Using the physiological processes that underlie the pathogenesis and progression of NAFLD as a framework, we review the literature describing currently available mouse models of NAFLD, highlight the strengths and weaknesses of established models and describe the key findings that have furthered the understanding of disease pathogenesis.
School experiences after treatment for a brain tumour
Authors: Upton P. , Eiser C. 
Published: January 2006

AbstractBackground Children surviving a brain tumour face major difficulties including learning problems, lengthy school absences and psychosocial problems, all of which can impact on school functioning. Our aims were to provide information for parents and teachers about the skills and resources of this group. Specifically, we aimed to:

describe the special educational needs of these children;
document the impact of diagnosis and treatment on school attendance;
compare parent and teacher assessments of social, emotional and behavioural difficulties.

Methods Forty families agreed to participate (response rate = 58.82%). The children (19 males and 21 females) were aged from 6 to 16 years and had completed treatment at least 2 years previously (range = 2 years−12 years 5 months). Questionnaires (Strengths and Difficulties and school experience) were completed by mothers and teachers.Results Survivors were experiencing a wide range of physical, learning and interpersonal difficulties, according to parent and teacher reports. Almost half the children (n = 19) had ongoing neurological problems that were significant enough to require special help at school. Literacy and numeracy were the most common learning difficulties. Parents also rated brain tumour survivors as having more behavioural and emotional problems than would be expected from population norms. For example, survivors were rated as having more Total Difficulties (t = 6.86, P < 0.001), Emotional Symptoms (t = 8.82, P < 0.001), Hyperactivity (t = 2.25, P = 0.03), Peer Relationship Problems (t = 7.58, P < 0.001) and poorer Pro‐social Behaviour (t = −3.34, P = 0.002) than would be expected from population norms. These problems were also seen to be having a significant impact on the child's functioning (t = 3.95, P < 0.001). Teachers rated these problems as less serious than parents.Conclusion These children experience significant problems in school some time after diagnosis and when they are considered medically cured. Closer school–hospital liaison is essential to maximize integration and achievement in these children.