bluuebunny/crossref_metadata_2025 huggingface dataset:
Pilot validation of the Boston Bowel Preparation Scale in China
Authors: Gao Yan , Lin Ju‐Sheng , Zhang Hou‐De , Lin Mu‐Xian , Cheng Chun‐Sheng , Wu Sheng‐Zhou
Published: July 2012

Background and Aim

The Boston Bowel Preparation Scale (BBPS) is a novel bowel cleanliness rating scale that has undergone validation at Boston University Medical Center, Boston, MA, USA. Thus far, there is no standard recognized bowel preparation scale in China. The aim of the present study was to analyze the reliability and validity of the BBPS for the assessment of bowel preparation quality (BPQ) in China.

Methods

A group of 49 participants from several hospitals in Guangdong province viewed a video demonstration of BBPS provided by Boston Medical Center and participated in a continuing education seminar. Inter‐observer reliability was assessed for three testing colonoscopies in the video. Three months later, 13 of the participants repeated the test, and intra‐observer reliability was assessed. The BBPS was then applied prospectively in 1012 screening colonoscopies and BBPS scores were compared with polyp‐detection rate. Intraclass correlation coefficients (ICC) and weighted Kappa values assessed inter‐ and intra‐rater reliability, respectively. The association of BBPS scores with polyp‐detection rates was calculated by χ2 tests.

Results

The inter‐observer ICC of BBPS scores was 0.987 (95% CI, 0.949–1.0). The weighted Kappa for BBPS scores was 0.671 (95%CI, 0.507–0.841). For 1012 screening colonoscopies, the mean BBPS score was 6.9 ± 1.8. BBPS scores ≥ 5 were associated with a higher polyp‐detection rate (35%) than scores < 5 (18%) (P < 0.05).

Conclusion

The BBPS is a valid and reliable measure of BPQ, and this validity and reliability was maintained for Chinese physicians taught via video.
Endoscopic diagnosis of gastric mucosal activity and inflammation
Authors: Nomura Sachiyo , Terao Shuichi , Adachi Kyoichi , Kato Takahiro , Ida Kazunori , Watanabe Hidenobu , Shimbo Takuro ,   the Research Group for Establishment of Endoscopic Diagnosis of Chronic Gastritis
Published: July 2012

Aim

Gastritis is an important pathological state that causes gastric atrophy and cancer. The Sydney System is a well‐used classification for histological evaluation for gastritis. However, there is no concordance with endoscopic findings. In the present study, we tried to establish endoscopic criteria and diagnosis for the inflammation activity of gastric mucosa.

Methods

A prospective multicenter study was conducted and 24 facilities participated. Two hundred and seventy patients received endoscopic examinations and 15 endoscopic features were evaluated. Biopsy specimens were taken from five points, and evaluated by a single pathologist for mononuclear cell infiltration and polymorphonuclear cell infiltration. Sensitivity, specificity, positive predictive value, negative predictive value, area under curve of receiver operating characteristics (AUC/ROC) of each endoscopic finding to histological gastritis were calculated.

Results

There was no single endoscopic finding that was highly specific for mononuclear cell infiltration and polymorphonuclear cell infiltration. In the corpus, the combination of swelling of areae gastrica by the indigo carmine contrast method (IC method) and lack of a regular arrangement of collecting venules (RAC) in angle for mononuclear cell infiltration (0.887), and the combination of swelling of areae gastrica by the IC method and diffuse redness for polymorphonuclear cell infiltration (0.851) showed the highest AUC/ROC. In the antrum, the combination of diffuse redness and visibility of a vascular pattern for mononuclear cell infiltration (0.780), and the combination of visibility of vascular pattern and swelling of areae gastrica by the IC method for polymorphonuclear cell infiltration (0.795) showed the highest AUC/ROC.

Conclusion

Combination of endoscopic findings can improve diagnostic accuracy, and sensitivity of examination for inflammation.
Satisfaction with joint replacement in public versus private hospitals: a cohort study
Authors: Adie Sam , Dao Alan , Harris Ian A. , Naylor Justine M. , Mittal Rajat
Published: July 2012

Introduction:  In Australia, the majority of total knee and hip replacement surgeries occur in the private sector. Outcome‐based research needs to be inclusive of this sector if the findings are intended to reflect the broader picture. This study compares outcomes up to 1 year post knee and hip replacement between patients treated in the public and private sectors.

Methods:  A prospective, observational study was performed in four high‐volume joint replacement centres: two public, two private. Experienced orthopaedic surgeons contributed via their public and private practices. Knee and hip patients were recruited preoperatively. Self‐reported questionnaires were completed preoperatively and at 6 and 12 months post‐operatively. The primary outcome was satisfaction with surgery. Secondary outcomes included Oxford score, and SF‐36 physical and mental component summary scores. Regression modelling was performed to adjust for potential confounders.

Results:  Three hundred and thirty‐one patients (184 public, 147 private; 215 knees, 116 hips) were recruited, with 6‐ and 12‐month follow‐up rates of 95% and 89%, respectively. Satisfaction rates were high in both public and private patients (approximately 90%) at 6 and 12 months, but private patients were less likely to be satisfied after adjusting for the strong effect of patient expectation. For both hip and knee cohorts, no between‐sector differences were found in either the magnitude or rate of improvement in Oxford score or quality of life post‐operatively.

Discussion:  Joint replacement outcomes are similar for patients treated in public and private hospitals. Surgeons should manage patient expectation prior to surgery, particularly in private patients.
Reliance on pollinators predicts defensive chemistry across tobacco species
Authors: Adler Lynn S. , Seifert Megan G. , Wink Michael , Morse Geoffrey E.
Published: July 2012

Defensive traits are typically studied in the context of avoiding antagonists, but may also mediate key interactions with mutualists. Plant chemical defences occur in flowers, suggesting pollinators may be agents of selection on defence. We hypothesised that floral defences would deter pollinators, and therefore, pollinators would select for lower defences in outcrossing than self‐pollinating species. We measured pollinator reliance and alkaloid levels in 32 greenhouse‐grown Nicotiana species. Using a comparative phylogenetic approach, we found significantly lower nectar, floral and leaf nicotine concentrations in outcrossing than selfing species, with a 15‐fold decrease in leaf nicotine levels. Nicotine concentrations were positively correlated across tissues, suggesting that selection against floral defences could constrain the evolution of leaf defences. Thus, pollinators could shape the evolution not only of floral defences but also of defences in other tissues where herbivores have traditionally been considered the dominant agent of selection.
Vacuolar respiration of nitrate coupled to energy conservation in filamentous Beggiatoaceae
Authors: Beutler Martin , Milucka Jana , Hinck Susanne , Schreiber Frank , Brock Jörg , Mußmann Marc , Schulz‐Vogt Heide N. , de Beer Dirk
Published: July 2012

We show that the nitrate storing vacuole of the sulfide‐oxidizing bacterium Candidatus Allobeggiatoa halophila has an electron transport chain (ETC), which generates a proton motive force (PMF) used for cellular energy conservation. Immunostaining by antibodies showed that cytochrome c oxidase, an ETC protein and a vacuolar ATPase are present in the vacuolar membrane and cytochrome c in the vacuolar lumen. The effect of different inhibitors on the vacuolar pH was studied by pH imaging. Inhibition of vacuolar ATPases and pyrophosphatases resulted in a pH decrease in the vacuole, showing that the proton gradient over the vacuolar membrane is used for ATP and pyrophosphate generation. Blockage of the ETC decreased the vacuolar PMF, indicating that the proton gradient is build up by an ETC. Furthermore, addition of nitrate resulted in an increase of the vacuolar PMF. Inhibition of nitrate reduction, led to a decreased PMF. Nitric oxide was detected in vacuoles of cells exposed to nitrate showing that nitrite, the product of nitrate reduction, is reduced inside the vacuole. These findings show consistently that nitrate respiration contributes to the high proton concentration within the vacuole and the PMF over the vacuolar membrane is actively used for energy conservation.
Molecular substitution rate increases in myrmecophilous lycaenid butterflies (Lepidoptera)
Authors: Pellissier Loic , Litsios Glenn , Guisan Antoine , Alvarez Nadir
Published: July 2012

Pellissier, L., Litsios, G., Guisan, A. & Alvarez, N. (2012). Molecular substitution rate increases in myrmecophilous lycaenid butterflies (Lepidoptera). —Zoologica Scripta, 41, 651–658.

Is species diversification driven by neutral‐ or niche‐based processes? Butterflies of the Lycaenidae family have developed mutualistic interactions with ants. This biotic requirement increased the spatial fragmentation of populations of lower effective population size (Ne) compared with autonomous species. The nearly neutral theory predicts that species with smaller Ne should fix more mutations because of the increased strength of drift. Taking into account the phylogenetic relatedness among species, this study shows that species with a stronger dependence on ants displayed more intra‐specific Single Nucleotide Polymorphisms compared with species with low or no myrmecophily. This phenomenon can cause more pronounced genetic differentiation between populations and could ultimately promote speciation in a similar manner as on physical islands. The large species diversity observed in this family could be the consequence of this neutral process enhancing the diversification of lineages.
Phylogenetic resolution and systematics of the Asian tree frogs, Rhacophorus (Rhacophoridae, Amphibia)
Authors: Li Jia‐Tang , Li Yang , Murphy Robert W. , Rao Ding‐Qi , Zhang Ya‐Ping
Published: July 2012

Li, J.T., Li, Y., Murphy, R.W., Rao, D.‐Q. & Zhang, Y.‐P. (2012). Phylogenetic resolution and systematics of the Asian tree frogs, Rhacophorus (Rhacophoridae, Amphibia). —Zoologica Scripta, 41, 557–570.

The treefrog genus Rhacophorus, a large genus with 80 species, has a wide range, occurring eastward from India to China, Japan, South‐east Asia, the Greater Sunda Islands and the Philippines. The phylogenetic relationships and taxonomic recognition of many species are very controversial. To stabilize the taxonomy, the phylogenetic relationships among about 52 species are investigated from 96 samples using mtDNA sequence data. Matrilineal relationships based on maximum likelihood and Bayesian inference methods resolve three well‐supported lineages (A, B and C), although the phylogenetic relationships among three lineages remain ambiguous. Analyses support recognition of two previously assigned subgenera, Leptomantis and Rhacophorus, and these correspond to lineages A and B, respectively. Given that we have three strongly supported lineages, that these lineages are morphologically distinct, and the constrained geographic distributions of these groups, we recognize each lineage as a taxon. Subgenus Leptomantis includes species mainly from Malaysia, Indonesia and the Philippines. Subgenus Rhacophorus contains a mix of species occurring in India, Indochina and southern China. Lineage C accommodates species distributed mostly in East Asia, including Japan and China. Based on genetic and morphological data from type localities, the taxonomic recognition of some species needs to be reconsidered. Rhacophorus pingbianensis and Polypedates spinus are considered as junior synonyms of Rhacophorus duboisi. Specimens of Rhacophorus rhodopus from Vietnam and Hainan, China likely represent an undescribed, cryptic species.
DISCRIMINATING SHORT AND LONG MEMORY IN FINITE SAMPLES USING SENSITIVITY ANALYSIS: AN APPLICATION TO GROWTH CONVERGENCE
Authors: Banerjee Anurag N.
Published: July 2012

The standard linear model where ut is generated from an ARFIMA process, is considered. The sensitivity of the predictor and sensitivity of variance estimates of the linear model to long memory are investigated by constructing the statistical measures BL/S and DL/S, respectively. BL/S and DL/S is interpreted as a sensitivity measure for the long‐memory process without the short‐memory effects. As an application, the memory characteristics of per capita GDP of 30 countries are investigated from the Maddison GDP dataset. It is found that per‐capita GDP exhibits long memory characteristics, and the long‐run growth estimates are sensitive to the long memory characteristics.
Z‐BAG: A CLASSIFICATION ENSEMBLE SYSTEM WITH POSTERIOR PROBABILISTIC OUTPUTS
Authors: Xu Zhonghui , Voichiţa Călin , Drăghici Sorin , Romero Roberto
Published: July 2012

Ensemble systems improve the generalization of single classifiers by aggregating the prediction of a set of base classifiers. Assessing classification reliability (posterior probability) is crucial in a number of applications, such as biomedical and diagnosis applications, where the cost of a misclassified input vector can be unacceptable high. Available methods are limited to either calibrate the posterior probability on an aggregated decision value or obtain a posterior probability for each base classifier and aggregate the result. We propose a method that takes advantage of the distribution of the decision values from the base classifiers to summarize a statistic which is subsequently used to generate the posterior probability. Three approaches are considered to fit the probabilistic output to the statistic: the standard Gaussian CDF, isotonic regression, and linear logistic. Even though this study focuses on a bagged support vector machine ensemble (Z‐bag), our approach is not limited by the aggregation method selected, the choice of base classifiers, nor the statistic used. Performance is assessed on one artificial and 12 real‐world data sets from the UCI Machine Learning Repository. Our approach achieves comparable or better generalization on accuracy and posterior estimation to existing ensemble calibration methods although lowering computational cost.
Insular stroke is associated with acute sympathetic hyperactivation and immunodepression
Authors: Walter U. , Kolbaske S. , Patejdl R. , Steinhagen V. , Abu‐Mugheisib M. , Grossmann A. , Zingler C. , Benecke R.
Published: July 2012

Background and purpose

Post‐stroke immunodepression has been related to brain lesion size but not a specific lesion location. Here, we studied the influence of lesion location within middle cerebral artery (MCA) territory on parameters related to activation of sympathetic adrenomedullar pathway, immunodepression, and associated infection.

Methods

We analyzed clinical, brain imaging, and laboratory data of 384 patients (174 women; mean age 70.8 ± 12.9 years) consecutively admitted to the stroke unit no later than 24 h after onset of acute ischaemic stroke involving the MCA territory.

Results

Patients with lesion affecting >33% of MCA territory had increased serum metanephrine and normetanephrine levels, elevated neutrophil counts but decreased eosinophil, helper T lymphocyte, and cytotoxic T lymphocyte counts compared to patients with lesion in <33% of MCA territory. Patients with large infarctions had increased frequency of infections within 14 days after stroke, especially chest infections (P < 0.001). Considering only patients with non‐lacunar infarction in <33% of MCA territory, those with insular lesion had significantly higher normetanephrine levels, higher neutrophil but lower eosinophil and helper T lymphocyte counts than those with non‐insular lesion, despite similar lesion diameters. This coincided with an increased frequency of chest infections (P < 0.01) in patients with insular lesion. Whilst patients with right insular lesion showed decreased heart rate variability, lesion laterality had no impact on laboratory findings or infection frequency.

Conclusion

These findings suggest a specific role of insular lesion in the pathogenesis of stroke‐induced sympathetic hyperactivation and immunodepression. Neuroimaging studies applying lesion volume calculation techniques are warranted to confirm these findings.
Risk factors for surgical site infection following caesarean section in England: results from a multicentre cohort study
Authors: Wloch C , Wilson J , Lamagni T , Harrington P , Charlett A , Sheridan E
Published: July 2012

Please cite this paper as: Wloch C, Wilson J, Lamagni T, Harrington P, Charlett A, Sheridan E. Risk factors for surgical site infection following caesarean section in England: results from a multicentre cohort study. BJOG 2012;119:1324–1333.

Objective  To assess the frequency and risk factors for surgical site infection following caesarean section.

Design  Prospective multicentre cohort study.

Setting  Fourteen NHS hospitals in England, April to September 2009.

Population  Women who underwent caesarean section at participating hospitals during designated study periods.

Methods  Infections that met standard case definitions were identified through active follow up by healthcare staff during the hospital stay, on return to hospital, during midwife home visits and through self‐completed patient questionnaires.

Main outcome measure  Surgical site infection within 30 days of operation.

Results  Altogether, 9.6% (394/4107) of women in the study developed a postsurgical infection following caesarean section with 0.6% (23/4107) readmitted for treatment of the infection. Being overweight (body mass index [BMI] 25–30 kg/m2 odds ratio [OR] 1.6, 95% confidence interval [95% CI] 1.2–2.2) or obese (BMI 30–35 kg/m2 OR 2.4, 95% CI 1.7–3.4; BMI > 35 kg/m2 OR 3.7, 95% CI 2.6–5.2) were major independent risk factors for infection (compared with BMI 18.5–25 kg/m2). There was a suggestion that younger women, and operations performed by associate specialist and staff grade surgeons had a greater odds of developing surgical site infection with OR 1.9, 95% CI 1.1–3.4 (<20 years versus 25–30 years), and OR 1.6, 95% CI 1.0–2.4 (versus consultants), respectively.

Conclusions  This study identified high rates of postsurgical infection following caesarean section. Given the number of women delivering by caesarean section in the UK, substantial costs will be incurred as a result of these infections. Prevention of these infections should be a clinical and public health priority.
Experiences of the individual placement and support approach in persons with severe mental illness
Authors: Areberg Cecilia , Björkman Tommy , Bejerholm Ulrika
Published: July 2012

Background:  Across several research studies comparing the individual placement and support (IPS) approach to traditional vocational services, the approach has achieved employment outcomes superior to comparison conditions. However, to understand the efficacy of IPS, it is equally important to consider what is more or less effective as viewed by the IPS participants.

Aim:  To investigate participants’ experiences of IPS participation and their experiences of receiving support from an employment specialist (ES).

Method:  Interviews were conducted with 17 persons with severe mental illness. The interviews were subjected to qualitative content analysis. The principles of informed consent and the voluntary nature of participation were included as ethical considerations.

Results:  Participation in IPS was associated with hope, meaning and an individualized support provided by the ES. The skills of the ES facilitated the relationship with the participant and the contact with the labour market. However, to make a change happen, everybody involved in IPS had to contribute.

Conclusion:  These findings have endorsed the guiding principles of IPS and emphasized the ES’s role and skills during IPS as well as the participant’s motivation.
Human serum metabolic profiles are age dependent
Authors: Yu Zhonghao , Zhai Guangju , Singmann Paula , He Ying , Xu Tao , Prehn Cornelia , Römisch‐Margl Werner , Lattka Eva , Gieger Christian , Soranzo Nicole , Heinrich Joachim , Standl Marie , Thiering Elisabeth , Mittelstraß Kirstin , Wichmann Heinz‐Erich , Peters Annette , Suhre Karsten , Li Yixue , Adamski Jerzy , Spector Tim D. , Illig Thomas , Wang‐Sattler Rui
Published: July 2012

Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age‐related metabolite concentration changes in human homeostasis. We report results from two population‐based studies: the KORA F4 study from Germany as a discovery cohort, with 1038 female and 1124 male participants (32–81 years), and the TwinsUK study as replication, with 724 female participants. Targeted metabolomics of fasting serum samples quantified 131 metabolites by FIA‐MS/MS. Among these, 71/34 metabolites were significantly associated with age in women/men (BMI adjusted). We further identified a set of 13 independent metabolites in women (with P values ranging from 4.6 × 10−04 to 7.8 × 10−42, αcorr = 0.004). Eleven of these 13 metabolites were replicated in the TwinsUK study, including seven metabolite concentrations that increased with age (C0, C10:1, C12:1, C18:1, SM C16:1, SM C18:1, and PC aa C28:1), while histidine decreased. These results indicate that metabolic profiles are age dependent and might reflect different aging processes, such as incomplete mitochondrial fatty acid oxidation. The use of metabolomics will increase our understanding of aging networks and may lead to discoveries that help enhance healthy aging.
A qualitative analysis of power‐based entrainment and interactional synchrony in couples
Authors: DUNBAR NORAH E. , MEJIA ROBERT
Published: July 2012

Interpersonal synchrony is a communicative lubricant that is associated with harmonious communication among conversational participants and is believed to be evidence of like‐mindedness and interpersonal solidarity. In this secondary analysis of an existing data set of both power‐equal and power‐unequal couples working through a discussion task, the content and form of their conversations were qualitatively examined for evidence of synchrony and dissynchrony. It was found that power‐equal couples tended toward synchronous communication and their conversations were represented by strategies that appeared either collaborative or competitive but generally respectful and problem oriented. The power‐unequal couples used one‐sided marginalization or withdrawal strategies that were characterized largely by dissynchrony. The theoretical implications for these findings are discussed.
Characterization of two new ETB selective radioligands, [125I]‐BQ3020 and [125I]‐[Ala1,3,11,15]ET‐1 in human heart
Authors: Molenaar Peter , Kuc Rhoda E. , Davenport Anthony P.
Published: July 2012

Two new endothelin receptor radioligands, [125I]‐BQ3020 and [125I]‐[Ala1,3,11,15]ET‐1, were characterized in tissue sections of human right atrium and left ventricle. Both radioligands had high affinity ([125I]‐BQ3020 right atrium: KD = 0.145 ± 0.037 nm, left ventricle: KD = 0.107 ± 0.004 nm; [125I]‐[Ala1,3,11,15]ET‐1 right atrium: KD = 0.239 ± 0.036 nm, left ventricle: KD = 0.199 ± 0.027 nm). Competition binding experiments were performed in the left ventricle. The selective ETA receptor compound BQ123 competed with low affinity against [125I]‐BQ3020 (KD = 28.7 ± 2.7 μm) and [125I]‐[Ala1,3,11,15]ET‐1 (KD = 28.5 ± 4.2 μm). The selective ETB receptor compound BQ3020 competed with high affinity against [125I]‐BQ3020 (KD = 40.8 ± 6.6 pm) and [125I]‐[Ala1,3,11,15]ET‐1 (KD = 0.276 ± 0.099 nm). Another selective ETB receptor compound, [Ala1,3,11,15]ET‐1 also competed with high affinity against [125I]‐BQ3020 (KD = 0.663 ± 0.120 nm) and [125I]‐[Ala1,3,11,15]ET‐l (KD = 0.643 ± 0.124 nm). These results indicate that [125I]‐BQ3020 and [125I]‐[Ala1,3,11,15]ET‐1 are selective ETB receptor radioligands. [Ala1,3,11,15]ET‐1 competed with the non‐selective radioligand [125I]‐ET‐1 in left ventricle and revealed the presence of ETA and ETB receptors in the proportions of 76:24% respectively in the human left ventricle.
Modulation of the induction of nitric oxide synthase by eicosanoids in the murine macrophage cell line J774
Authors: Marotta Principia , Sautebin Lidia , Di Rosa Massimo
Published: July 2012

The effect of eicosanoids on the induction of nitric oxide synthase in the murine macrophage cell line J774 has been studied. We found that prostaglandin E2 (PGE2) and iloprost (a stable analogue of prostacyclin) both at nanomolar concentrations inhibited the lipopolysaccharide stimulated induction of NO synthase. In contrast PGF2α, U46619, a stable analogue of thromboxane A2, leukotrienes B4 and C4 had no effect. These data demonstrate that the l‐arginine: NO pathway in macrophages may be modulated by prostanoids.
Preconditioning of the ischaemic myocardium; involvement of the l‐arginine nitric oxide pathway
Authors: Vegh Agnes , Szekeres Laszlo , Parratt James
Published: July 2012

Short periods of coronary artery occlusion protect the heart against the effects of a subsequent prolonged period of ischaemia. This phenomenon is known as preconditioning of the ischaemic myocardium.

In mongrel, chloralose‐urethane anaesthetized open‐chest dogs, within a restricted body weight range, two 5 min periods of occlusion of the anterior descending branch of the left coronary artery markedly reduced the severity of the early ischaemic arrhythmias resulting from a prolonged (25 min) occlusion of the same coronary artery starting 20 min later. Thus, the number of ventricular premature beats (VPBs) was reduced from 528 ± 140 in controls to 78 ± 27 in preconditioned dogs, the incidence of ventricular fibrillation (VF) was reduced from 47% to 0% and the incidence of ventricular tachycardia (VT) from 100% to 20%. ST‐segment elevation recorded from electrodes within the ischaemic area, and the degree of inhomogeneity of conduction within the ischaemic area were markedly reduced in these preconditioned dogs.

The incidence of VF following reperfusion of the ischaemic myocardium at the end of the 25 min occlusion period was reduced in the preconditioned dogs from 100% to 60%; there was thus a 40% survival from the combined ischaemia‐reperfusion insult compared with 0% in the controls.

NG‐nitro‐l‐arginine methyl ester (l‐NAME) an inhibitor of the l‐arginine nitric oxide pathway, given in a dose of 10 mg kg−1 intravenously on two occasions, both before the initial preconditioning occlusion and then again before the prolonged occlusion, partially attenuated the protective effects of preconditioning. There were more VPBs (220 ± 75), a higher incidence of VT (60%) and more episodes of VT (11.5 ± 6.0 compared to 0.7 ± 0.3 episodes in the preconditioned dogs not given l‐NAME); none of the animals survived reperfusion (incidence of VF 100%). The improvement in the severity of the degree of inhomogeneity which resulted from preconditioning was abolished by l‐NAME administration.

l‐NAME itself elevated blood pressure (from 96 ± 5 mmHg diastolic to 119 ± 7 mmHg), reduced heart rate (from 155 ± 7 to 144 ±4 beats min−1) but did not change LVEDP, LVdP/dtmax, coronary blood flow, ST‐segment elevation or the degree of inhomogeneity of conduction. When given 10 min before the prolonged coronary artery occlusion in dogs not subjected to preconditioning, l‐NAME had no significant effect on the severity of arrhythmias except for more periods of VT (a mean of 11.7 ± 4.7 episodes per dog).

It is concluded from these studies that the generation of nitric oxide contributes to the marked antiarrhythmic effects of preconditioning in the canine myocardium, probably through elevation of cyclic GMP.
Effects of bradykinin receptor antagonists on antigen‐induced respiratory distress, airway hyperresponsiveness and eosinophilia in guinea‐pigs
Authors: Farmer Stephen G. , Wilkins Deidre E. , Meeker Sonya A. , Seeds Esther A.M. , Page Clive P.
Published: July 2012

We examined effects of bradykinin (BK) receptor antagonists on airway hyperresponsiveness and eosinophilia in sensitized guinea‐pigs that had been administered single, as well as repeated (chronic) challenges with inhaled ovalbumin. In addition, the effects of BK antagonists on antigen‐induced respiratory distress during the chronic study were noted.

At 24 h following single antigen challenge, guinea‐pigs exhibited airway hyperresponsiveness to the bronchoconstrictor effect of i.v. histamine, characterized by a left shift in the dose‐response curve. In addition, responses to the maximum dose of histamine that could be used were significantly increased in hyperresponsive guinea‐pigs. The percentages of bronchoalveolar fluid, eosinophil and neutrophils also increased.

A BK B1 receptor antagonist, desArg9‐[Leu8]‐BK, significantly inhibited airway hyperresponsiveness induced by single antigen challenge. A B2 receptor antagonist, d‐Arg‐[Hyp3, Thi5,8,d‐Phe7]‐BK (NPC 349) had a small, but statistically significant inhibitory effect on responsiveness to the highest histamine dose in challenged animals. DesArg9‐[Leu8]‐BK significantly inhibited the neutrophilia, whereas NPC 349 inhibited infiltration by both cell types.

Chronic antigen challenge also caused airway hyperresponsiveness to i.v. acetylcholine (ACh), distinguished by an increase in the slope of the dose‐response curve. Thus, the magnitude of the bronchoconstrictor responses to the maximum dose of ACh that could be used was significantly increased. No change in sensitivity to ACh was evident. Marked eosinophilia was also noted in the trachea, bronchi and lung parenchyma.

Airway hyperresponsiveness and eosinophilia, induced by chronic antigen challenge, were markedly inhibited by the B2 antagonists, d‐Arg‐[Hyp3,d‐Phe7]‐BK (NPC 567) or d‐Arg‐[Hyp3,Thi5d‐Tic7,Tic8]‐BK (NPC 16731). NPC 16731 also abolished antigen‐induced cyanosis, and delayed the onset of dyspnoea, doubling the time taken for animals to exhibit respiratory distress.

The ability of BK receptor antagonists to inhibit antigen‐induced airway hyperresponsiveness, in addition to eosinophilia, indicates an important role for endogenous kinins. Moreover, the abrogation of eosinophil infiltration suggests that BK has a significant function in maintaining allergic inflammation of the airways.
In vitro effect of oestradiol on thymidine uptake in pulmonary vascular smooth muscle cell: role of the endothelium
Authors: Farhat Michel Y. , Vargas Roberto , Dingaan Brenda , Ramwell Peter W.
Published: July 2012

The effect of different concentrations of oestradiol‐17β (3–300 nm) on [3H]‐thymidine uptake was studied in segments from canine pulmonary artery, and cultures of rat pulmonary vascular smooth muscle cells (VSMC).

Incubation with oestradiol‐17β for 24 h, potentiated in a concentration‐dependent manner [3H]‐thymidine uptake in VSMC cultures.

Oestradiol‐17β potentiated thymidine uptake by pulmonary arterial segments but only when the endothelium had been removed. Autoradiography showed dense incorporation of radioactive thymidine in the vascular smooth muscle cells of the media.

The non‐steroidal oestrogen, stilboestrol (300 nm), also significantly potentiated [3H]‐thymidine uptake, in both VSMC cultures and pulmonary artery segments. Testosterone was ineffective at a similar concentration.

Pre‐incubation of the pulmonary VSMC with the anti‐oestrogen tamoxifen (1 μm) antagonized the potentiating effect of oestradiol‐17β on [3H]‐thymidine incorporation. The effect of tamoxifen was less pronounced in pulmonary arterial segments.

These data suggest that oestrogen may promote proliferation of pulmonary VSMC. Endothelial injury or dysfunction may be an important factor in the expression of the oestrogenic effect.

We speculate that plasma oestrogen may be a contributing factor to the proliferative lesion observed in certain forms of pulmonary vascular injury in women.
Novel signal transduction pathway mediating endothelium‐dependent β‐adrenoceptor vasorelaxation in rat thoracic aorta
Authors: Gray David W. , Marshall Ian
Published: July 2012

Isoprenaline (3 × 10−8−10−5 m), salbutamol (3 × 10−7−10−4 m) and forskolin (3 × 10−9−3 × 10−7 m) relaxed rat isolated thoracic aortic rings contracted with noradrenaline (10−7 m). Removal of the endothelium from the aortic rings abolished the effect of acetylcholine (10−6 m) and completely prevented the vascular relaxation induced by isoprenaline, salbutamol or forskolin.

The isoprenaline concentration‐relaxation curve was shifted in parallel to the right about 10 fold by propranolol (3 × 10−7 m) with no change in the maximum response, showing that the relaxation was mediated by a β‐adrenoceptor.

The inhibitor of nitric oxide synthesis, NG‐nitro‐l‐arginine (l‐NOARG; 10−5 m), shifted the isoprenaline relaxation curve to the right and reduced the maximum response.

Isoprenaline (10−6 m) relaxed noradrenaline‐induced tone by approximately 95% and at the same time increased levels of adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) 4 fold and guanosine 3′:5′‐cyclic monophosphate (cyclic GMP) 12 fold in the aortic rings. Sodium nitroprusside (3 × 10−8 m) relaxed noradrenaline‐evoked tone by 82% without changing levels of cyclic AMP but raised cyclic GMP 19 fold.

Forskolin (10−7 m) relaxed noradrenaline‐induced tone by approximately 41% and, like isoprenaline, increased levels of cyclic AMP (2.5 fold) and cyclic GMP (12 fold) in the aortic rings.

Removal of the endothelium abolished the relaxant effects of isoprenaline (10−6 m) and also the associated accumulation of cyclic AMP and cyclic GMP.

l‐NOARG (10−5 m) inhibited the relaxant responses and accumulation of cyclic GMP induced by isoprenaline (10−6 m) and forskolin (10−7 m) without affecting the associated cyclic AMP accumulation.

It is concluded that, in the rat aorta, isoprenaline acts through a β‐adrenoceptor on the endothelium to raise cyclic AMP and that this may, directly or indirectly, release nitric oxide to evoke vascular relaxation via the increase in cyclic GMP. The importance of this novel transduction pathway for cardiovascular regulation remains to be determined.
Effects of the PAF antagonists BN50726 and BN50739 on arrhythmogenesis and extent of necrosis during myocardial ischaemia/reperfusion in rabbits
Authors: Chakrabarty Sisiresh , Fluck David S. , Flores Nicholas A. , Sheridan Desmond J.
Published: July 2012

The effects of two novel platelet activating factor (PAF) antagonists BN50726 and BN50739 on arrhythmias, haemodynamics and extent of necrosis during myocardial ischaemia and reperfusion were investigated in anaesthetized rabbits subjected to coronary artery ligation.

BN50739 reduced heart rate prior to coronary artery occlusion (P < 0.005) but had no other significant haemodynamic effects at this time. BN50739 and BN50726 did not significantly alter heart rate or blood pressure during 30 min of ischaemia or 30 min of reperfusion, compared to control hearts.

BN50739 and BN50726 had no effect on the incidence of arrhythmias during ischaemia. BN50726 significantly reduced the incidence of reperfusion ventricular fibrillation compared to controls (0% v 40%, P < 0.05), and improved survival (80% v 39%, P < 0.05). Similar trends were observed with BN50739.

BN50726 reduced the extent of necrosis compared to control hearts (18 ± 2% v 30 ± 3%, P <0.01). A similar trend was observed with BN50739.

These results demonstrate that PAF antagonism with BN50726 attenuates reperfusion‐induced arrhythmias and preserves myocardium in the early phase of ischaemia, independently of haemodynamic effects.
Chronic antihypertensive treatment with captopril plus hydrochlorothiazide improves aortic distensibility in the spontaneously hypertensive rat
Authors: Chillon Jean‐Marc , Capdeville‐Atkinson Christine , Lartaud Isabelle , Guillou Joel , Mertès Paul‐Michel , Atkinson Jeffrey
Published: July 2012

Adult male spontaneously hypertensive rats (SHR) were given captopril plus hydrochlorothiazide mixed in the diet for 10 weeks. Calculated daily doses were 44 mg kg−1 per day for captopril, and 22 mg kg−1 per day for hydrochlorothiazide. Separate groups received captopril or hydrochlorothiazide alone, at similar doses, or no treatment. A final group of WKY normotensive rats received no drug.

Systolic arterial blood pressure, measured at regular intervals throughout the 10 weeks' period was lowered but not normalized, in groups receiving either captopril plus hydrochlorothiazide, or captopril alone, but not in the group receiving hydrochlorothiazide alone.

Following pentobarbitone anaesthesia, systolic arterial blood pressure, measured in the femoral artery, was found to be lower in all treated groups, but the greatest effect was observed in SHR previously treated with captopril plus hydrochlorothiazide. Aortic pulse wave velocity was also lower in treated SHR, and once again the greatest decrease was observed in the group previously treated with captopril plus hydrochlorothiazide.

Following pithing, systolic arterial blood pressures were similar in all SHR groups. Aortic pulse wave velocity was lower in pithed rats previously treated with captopril and hydrochlorothiazide.

In conclusion, antihypertensive treatment of SHR produces falls in blood pressure and pulse wave velocity, an indicator of aortic distensibility. Results in pithed rats suggest that treatment with the combination of captopril plus hydrochlorothiazide may increase aortic distensibility independently of blood pressure.
An investigation of some S‐nitrosothiols, and of hydroxy‐arginine, on the mouse anococcygeus
Authors: Gibson A. , Babbedge R. , Brave S.R. , Hart S.L. , Hobbs A.J. , Tucker J.F. , Wallace P. , Moore P.K.
Published: July 2012

The effect of five S‐nitrosothiols, and of the stereoisomers of NG‐hydroxy‐arginine (HOARG), were investigated on the mouse anococcygeus.

All five S‐nitrosothiols produced concentration‐related (0.1–100 μm) relaxations of carbachol (50 μm)‐induced tone; the order of potency was S‐nitroso‐l‐cysteine (CYSNO) > S‐nitroso‐N‐acetyl‐d,l‐penicillamine (SNAP) > S‐nitrosoglutathione (GSNO) > S‐nitrosocoenzyme A (CoASNO) > S‐nitroso‐N‐acetyl‐l‐cysteine (NACNO). The relaxations were unaffected by the nitric oxide synthase (NOS) inhibitor, l‐NG‐nitro‐arginine (10 μm) (l‐NOARG).

Cold‐storage of the tissue for 72 h resulted in loss of sympathetic and non‐adrenergic, non‐cholinergic (NANC) nerve function. NOS activity in the tissue was reduced by 97%. Despite this, relaxations induced by the S‐nitrosothiols were unaffected.

Haemoglobin (50 μm) attenuated relaxations induced by NO and the S‐nitrosothiols, although responses to 3‐isobutyl‐1‐methyl‐xanthine were unaffected. N‐methyl‐hydroxylamine (2 Mm) which has been shown previously to produce selective inhibition of NANC and nitrovasodilator responses in this tissue, also reduced responses to all S‐nitrosothiols.

Hydroquinone (100 μm) greatly reduced relaxations to CYSNO (by 88%) but had no effect on those to SNAP, GSNO, CoASNO or NACNO. Since hydroquinone does not reduce responses to NANC stimulation, CYSNO is unlikely to be the NANC transmitter.

l‐HOARG by itself (up to 100 μm) had no significant effect on carbachol‐induced tone or on NANC (10 Hz; 10 s train every 100 s) relaxations. However, it produced reversal of the inhibitory effects of l‐NOARG (10 μm), being only slightly less potent than l‐arginine. d‐HOARG was without effect. l‐HOARG had no effect on relaxations induced by 1.5 μm NO.

The results show that S‐nitrosothiols are potent relaxants of the mouse anococcygeus; they act directly on the smooth muscle with a mechanism similar to NO and other nitrovasodilators. In addition, the results are consistent with l‐HOARG being an intermediate in the biosynthesis of NO from l‐arginine, although there is no evidence for it acting to stabilize NO extracellularly.
Contribution of NO and cytochrome P450 to the vasodilator effect of bradykinin in the rat kidney
Authors: Fulton D. , McGiff J.C. , Quilley J.
Published: July 2012

Inhibition of nitric oxide generation with Nw‐nitro‐l‐arginine (nitroarginine) reduced vasodilator responses to bradykinin and acetylcholine and enhanced those to nitroprusside in the rat isolated perfused kidney, preconstricted with phenylephrine.

Inhibition of cyclo‐oxygenase with indomethacin, decreased the vasodilator responses to bradykinin by ∼25% without affecting those to acetylcholine or nitroprusside.

BW755c, a dual inhibitor of cyclo‐oxygenase and lipoxygenase, reduced renal vasodilator responses to bradykinin, comparable to the effect of indomethacin suggesting an effect related to inhibition of cyclo‐oxygenase rather than lipoxygenase.

ETYA, an inhibitor of all arachidonic acid metabolic pathways, markedly reduced vasodilator responses to bradykinin but was without effect on the renal vasodilatation induced by acetylcholine or nitroprusside.

Clotrimazole and 7‐ethoxyresorufin, inhibitors of cytochrome P450, greatly attenuated vasodilator responses to bradykinin without affecting those to acetylcholine or nitroprusside.

These data suggest that the renal vasodilator response to bradykinin is subserved by arachidonic acid metabolites as well as nitric oxide, the former accounting for up to 70% of the vasodilator effect of bradykinin.
The pharmacology of recombinant GABAA receptors containing bovine α1, β1, γ2L sub‐units stably transfected into mouse fibroblast L‐cells
Authors: Home A.L. , Hadingham K.L. , Macaulay A.J. , Whiting P. , Kemp J.A.
Published: July 2012

Responses to γ‐aminobutyric acid (GABA) were evoked in mouse fibroblast L‐cells stably transfected with bovine, α1, β1, γ2L sub‐units of the GABAA receptor. Expression was stimulated via a steroid‐inducible promoter system.

In near symmetrical intracellular and extracellular chloride concentrations, GABA evoked inward currents at negative holding potentials that reversed at + 5 mV and displayed slight outward rectification. Concentration‐response curves were fitted well by the logistic equation. GABA had a pEC50 = 5.1 ± 0.1 and the curves had a slope of 1.9 ± 0.1

Responses to GABA were antagonized by bicuculline, picrotoxin and penicillin. The action of bicuculline was competitive (pA2 = 6.4) whilst the block by picrotoxin was uncompetitive and strongly agonist‐dependent.

Benzodiazepine receptor agonists potentiated responses to 3 μm GABA. The rank order of potency was FG 8205 > flunitrazepam > Zolpidem > C1218872. FG 8205 and C1218872 produced markedly lower maximal potentiations with efficacies 0.4 and 0.6 × that of flunitrazepam, respectively. The potencies of Zolpidem and C1218872 observed are in agreement with the BZ1 type pharmacology of this sub‐unit combination. The potentiation of GABA by flunitrazepam was antagonized by flumazenil with a Ki of 3.8 nm.

GABA responses were potentiated in the presence of pentobarbitone and alphaxalone. The response was also noticeably broadened by these compounds due to a decrease in the response decay rate. Concentrations of pentobarbitone of 100 μm and above evoked an inward current in the absence of GABA. Alphaxalone up to 10 μm did not evoke a direct response.

This expression system produced functional receptors that behaved in a fashion analogous to those found endogenously in other preparations. Thus, this system appears to provide a useful and versatile preparation for the analysis of sub‐unit regulation of GABAA receptor pharmacology.
S‐nitroso‐glutathione inhibits platelet activation in vitro and in vivo
Authors: Radomski Marek W. , Rees Daryl D. , Dutra Alberto , Moncada Salvador
Published: July 2012

The effect of S‐nitroso‐glutathione (GSNO), a stable nitrosothiol, on platelet activation was examined in vitro and in vivo.

The adhesion of human platelets to fibrillar collagen and human endothelial cell monolayers was inhibited by GSNO.

GSNO caused a concentration‐dependent inhibition of collagen‐induced platelet aggregation in vitro and decreased ADP‐induced aggregation in the conscious rat.

Inhibition of platelet aggregation in vitro correlated with the increase in intraplatelet cyclic GMP levels.

The release of NO from GSNO was enhanced by platelet lysate, native glutathione and ascorbate.

The results show that GSNO is a carrier of NO and therefore has pharmacological activity as an inhibitor of platelet activation.
Use of selective antagonists to dissociate the central cardiovascular and behavioural effects of tachykinins on NK1 and NK2 receptors in the rat
Authors: Tschöpe Carsten , Picard Pierre , Culman Juraj , Prat Alexandre , Itoi Keiichi , Regoli Domenico , Unger Thomas , Couture Réjean
Published: July 2012

The effects of intracerebroventricular (i.c.v.) pretreatment with selective NK1 ((±)‐CP 96,345), NK2a (MEN 10,207; MEN 10,376) and NK2b (R 396) tachykinin receptor antagonists on the cardiovascular and behavioural responses to i.c.v. substance P (SP) and neurokinin A (NKA) were studied in conscious rats.

SP and NKA (25 pmol) induced mean arterial blood pressure and heart rate increases of the same magnitude and duration. The cardiovascular responses to both peptides were accompanied by excessive face washing, sniffing, grooming and wet dog shakes.

The cardiovascular responses to SP but not to NKA were attenuated by pretreatment with a NK1 receptor antagonist, (±)‐CP 96,345. Of the behavioural responses, only face washing was significantly inhibited.

The cardiovascular and behavioural effects of NKA but not of SP were significantly attenuated by pretreatment with the selective NK2b receptor antagonist, R 396.

The selective NK2a receptor antagonists, MEN 10,207 and MEN 10,376, did not affect the cardiovascular and behavioural responses to either SP or NKA.

These results suggest, firstly, that the cardiovascular and behavioural effects of i.c.v. SP are mediated by NK1 receptors; secondly, that NKA injected i.c.v. does not interact with NK1 receptors but with another type of tachykinin receptor which may belong to the NK2b subclass. These findings provide pharmacological evidence for the existence of functionally active NK2 receptors in the rat brain.
(±)‐CP‐96,345, a selective tachykinin NK1 receptor antagonist, has non‐specific actions on neurotransmission
Authors: Wang Zun‐Yi , Håkanson Rolf
Published: July 2012

The non‐specific effects of the non‐peptide tachykinin receptor antagonist (±)‐CP‐96,345, were assessed in several smooth muscle‐nerve preparations. The preparations were the iris sphincter muscle of the rabbit and the taenia coli, vas deferens and seminal vesicle of the guinea‐pig.

(±)‐CP‐96,345 concentration‐dependently inhibited the elctrically evoked, tachykinin‐mediated contractile responses of the iris sphincter and the taenia coli. The pIC50 values were 5.4 ± 0.2 (mean ± s.e.mean) and 5.7 ± 0.08 respectively.

(±)‐CP‐96,345 also inhibited non‐tachykinin‐mediated contractile responses to electrical stimulation of the iris sphincter, taenia coli, vas deferens and seminal vesicle. The pIC50 values were 4.3 ± 0.02, 4.8 ± 0.03, 4.7 ± 0.02 and 4.4 ± 0.05 respectively. These values differ significantly from the pIC50 values of the inhibition of the tachykinin‐mediated response in the iris sphincter and taenia coli.

(±)‐CP‐96,345 was without effect on carbachol‐ and noradrenaline‐evoked contractions of the iris sphincter but inhibited carbachol‐ and prostaglandin F2α (PGF2α)‐evoked contractions of the taenia coli.

We suggest that (±)‐CP‐96,345, apart from its NK1 receptor blocking activity, induces non‐specific suppression of neurotransmission, exerted at both pre‐ and post‐junctional sites.