bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolving mechanisms of action of alverine citrate on phasic smooth muscles
Authors: Hayase M , Hashitani H , Suzuki H , Kohri K , Brading A F 
Published: October 2007

Background and purpose:We have investigated the mechanisms underlying the paradoxical ability of the antispasmodic, alverine, to enhance spontaneous activity in smooth muscles while suppressing evoked activity.Experimental approach:The effects of alverine on spontaneous and induced contractile activity were examined in preliminary experiments with various smooth muscles. More detailed effects were also investigated by recording membrane potential, intracellular Ca2+ concentration ([Ca2+]i) and tension from single‐bundle detrusor smooth muscle (DSM) of the guinea‐pig urinary bladder.Key results:Alverine (10 μM) increased the frequency and amplitude of spontaneous action potentials, transient increases in [Ca2+]i and associated contractions. Alverine also decreased action potential rate of decay, suggesting inhibition of L‐type Ca channel inactivation. Charybdotoxin (50 nM) but neither cyclopiazonic acid (10 μM) nor Bay K 8644 (10 μM) attenuated alverine‐induced enhancement of spontaneous contractions. Alverine suppressed contractions produced by high K (40 mM) or ACh (10 μM), without affecting electrical responses and with little suppression of increases in [Ca2+]i. This feature was very similar to that of the effects of the Rho kinase inhibitor Y‐27632 (10 μM).Conclusions and implications:Alverine may increase Ca influx during action potentials due to inhibition of the inactivation of L‐type Ca channels, but may also suppress evoked activity by inhibiting the sensitivity of contractile proteins to Ca2+. The proportional contribution of Ca‐dependent and Ca‐independent contractions in DSM may differ between spontaneous and evoked activity, necessitating further investigations into the interactions between these pathways for assessing the therapeutic potential of alverine to treat DSM dysfunction.British Journal of Pharmacology (2007) 152, 1228–1238; doi:10.1038/sj.bjp.0707496; published online 15 October 2007
Demethylnobiletin inhibits delayed‐type hypersensitivity reactions, human lymphocyte proliferation and cytokine production
Authors: Bas E , Recio M C , Giner R M , Máñez S , López‐Ginés C , Gil‐Benso R , Ríos J L 
Published: October 2007

Background and purpose:Our aim was to examine the effect of demethylnobiletin on various experimental models of delayed‐type hypersensitivity (DTH) reactions and to determine its influence on the mediators and enzymes involved in these reactions.Experimental approach:DTH was induced in mice by oxazolone, dinitrofluorobenzene (DNFB) and sheep red blood cells (SRBC). The effect of demethylnobiletin on the ensuing DTH was studied, especially in relation to oedema formation, cell infiltration and tissue damage. Its activity on different mediators implicated in DTH reactions was also determined and its effect on nitric oxide synthase (NOS)‐2 analysed. Finally, its influence on T lymphocyte proliferation, apoptosis and caspase 3 activity was tested.Key results:DTH reactions were all reduced by demethylnobiletin. The experimental results suggest that the compound may act by reducing cell infiltration and by suppressing mediators such as interleukin‐2 (IC50=1.63 μM), interleukin‐4 (IC50=2.76 μM), tumour necrosis factor‐α (IC50=0.66 μM), interferon‐γ (IC50=1.35 μM), and interleukin‐1β (46% at 2.5 μM) and by concomitantly increasing the production of the anti‐inflammatory cytokine, interleukin‐10. In addition, while demethylnobiletin affected nitric oxide production, it did not modify NOS‐2 expression. Finally, demethylnobiletin inhibited proliferation of T cells and induced their apoptosis.Conclusions and implications:Demethylnobiletin decreased DTH reactions induced by various agents. This finding, along with the fact that the compound has a low toxicity and exhibits several other interesting properties, could pave the way for other structurally related citroflavonoids to be used as pharmacological agents in complementary therapies.British Journal of Pharmacology(2007)152, 1272–1282; doi:10.1038/sj.bjp.0707500; published online 15 October 2007
An assessment of the in vivo efficacy of the glycogen phosphorylase inhibitor GPi688 in rat models of hyperglycaemia
Authors: Poucher S M , Freeman S , Loxham S J G , Convey G , Bartlett J B , De Schoolmeester J , Teague J , Walker M , Turnbull A V , Charles A D , Carey F , Berg S 
Published: October 2007

Background and purpose:Studies in cultured hepatocytes demonstrate glycogen synthase (GS) activation with glycogen phosphorylase (GP) inhibitors. The current study investigated whether these phenomena occurred in vivo using a novel GP inhibitor.Experimental approach:An allosteric GP inhibitor, GPi688, was evaluated against both glucagon‐mediated hyperglycaemia and oral glucose challenge‐mediated hyperglycaemia to determine the relative effects against GP and GS in vivo.Key results:In rat primary hepatocytes, GPi688 inhibited glucagons‐mediated glucose output in a concentration dependent manner. Additionally GP activity was reduced and GS activity increased seven‐fold. GPi688 inhibited glucagon‐mediated hyperglycaemia in both Wistar (65%) & obese Zucker (100%) rats and demonstrated a long duration of action in the Zucker rat. The in vivo efficacy in the glucagon challenge model could be predicted by the equation; % glucagon inhibition=56.9+34.3[log ([free plasma]/rat IC50)], r=0.921). GPi688 also reduced the blood glucose of obese Zucker rats after a 7 h fast by 23%. In an oral glucose tolerance test in Zucker rats, however, GPi688 was less efficacious (7% reduction) than a glycogen synthase kinase‐3 (GSK‐3) inhibitor (22% reduction), despite also observing activation (by 45%) of GS in vivo.Conclusions and implications:Although GP inhibition can inhibit hyperglycaemia mediated by increased glucose production, the degree of GS activation induced by allosteric GP inhibitors in vivo, although discernible, is insufficient to increase glucose disposal. The data suggests that GP inhibitors might be more effective clinically against fasting rather than prandial hyperglycaemic control.British Journal of Pharmacology (2007) 152, 1239–1247; doi:10.1038/sj.bjp.0707502; published online 15 October 2007
P2X1and P2X4receptor currents in mouse macrophages
Authors: Sim J A , Park C‐K , Oh S B , Evans R J , North R A 
Published: October 2007

Background and purpose:Activation of P2X receptors on macrophages is an important stimulus for cytokine release. This study seeks evidence for functional expression of P2X receptors in macrophages that had been only minimally activated.Experimental approach:Whole‐cell recordings were made from macrophages isolated 2–6 h before by lavage from mouse peritoneum, without further experimental activation. ATP (1–1000 μM) elicited inward currents in all cells (holding potential −60 mV). The properties of this current were compared among cells from wild type, P2X1−/−and P2X4−/−mice.Key results:Immunoreactivity for P2X1and P2X4receptors was observed in wild type macrophages but was absent from the respective knock‐out mice. In cells from wild type mice, ATP and αβmethyleneATP (αβmeATP) evoked inward currents rising in 10–30 ms and declining in 100–300 ms: these were blocked by pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS, 10 μM). ATP also elicited a second, smaller (∼10% peak amplitude), more slowly decaying (1–3 s) at concentrations 10 μM: this was resistant to PPADS and prolonged by ivermectin. Macrophages from P2X1−/−mice responded to ATP (>100 μM) but not αβmeATP: these small currents were prolonged by ivermectin. Macrophages from P2X4−/−mice responded to ATP and αβmeATP as cells from wild type mice, except that ATP did not evoke the small, slowly decaying component: these currents were blocked by PPADS.Conclusion:Mouse peritoneal macrophages that are minimally activated demonstrate membrane currents in response to ATP and αβmeATP that have the predominate features of P2X1receptors.British Journal of Pharmacology(2007)152, 1283–1290; doi:10.1038/sj.bjp.0707504; published online 15 October 2007
Cannabinoid CB2 receptors in human brain inflammation
Authors: Benito C , Tolón R M , Pazos M R , Núñez E , Castillo A I , Romero J 
Published: October 2007

The presence of functional cannabinoid CB2 receptors in the CNS has provoked considerable controversy over the past few years. Formerly considered as an exclusively peripheral receptor, it is now accepted that it is also present in limited amounts and distinct locations in the brain of several animal species, including humans. Furthermore, the inducible nature of these receptors under neuroinflammatory conditions, in contrast to CB1, makes them attractive targets for the development of novel therapeutic approaches. In fact, the undesired psychoactive effects caused by CB1 activation have largely limited the clinical use of cannabinoid‐related compounds that act on these receptors. In this review some recent findings on the antiinflammatory properties of CB2 receptors are presented, as well as new perspectives that have been obtained based on studies of human postmortem brain samples. In addition, various working hypotheses are also proposed and discussed.British Journal of Pharmacology (2008) 153, 277–285; doi:10.1038/sj.bjp.0707505; published online 15 October 2007
Niccolo Machiavelli: 1527–1927
Authors: Bugeja Henry 
Published: October 2007

On the 22nd of June, four hundred years ago, Niccolo Machiavelli died at San Casciano, not far from Florence, where he had lived since his dismissal from the office of Secretary to the Florentine Republic in 1512. A typical representative of his times, although his life, habits and ideals were those of a pagan, he died a Christian death : all the neo-pag'ans of the Italian Renaissance did the same. It was the fashion.A broken and disappointed man, discarded by the Medici, to whom in vain he had offered his services and experience, ready to sacrifice his political convictions if they could employ him, were it only in rolling a stone,’ suspected by his old political friends as one who fawned on princes and a traitor to the Republican cause, Machiavelli passed the last few years of his life cursing fate, fighting against poverty and chafing under this enforced idleness, which to a man of his undoubted capabilities, accustomed for many a year to transact diplomatic business with the most renowned princes of the epoch, must have been truly unbearable. It is with pity and sympathy, not unmingled with a sense of disgust, that one reads Machiavelli’s own account of how he used to pass his days in the semiexile of San Casciano. Rising at dawn, after passing a couple of hours in the woods of the estate he used to go and sit by a spring reading Dante, Petrarch, Tibullus and Ovid, meditating pleasantly on ‘their amorous transports and the history of their loves’ ; thence betaking himself to an inn by the roadside to gossip with passers-by and ‘note the varied tastes and diverse fancies of mankind. . . . Dinner over, I go back to the inn.
Poles and Parallels of Culture
Authors: Kincaid Dennis 
Published: October 2007

It is not often that a book excites such comment as did Spengler’s Decline of the West in postwar Germany. Only the first volume of this has been translated into English, as yet. It is an exposition of determinism involving the methodic rise and fall of cultures. And in spite of some exaggerations, and the arbitrariness of its thesis, it is of the greatest interest. Possibly its greatest value lies in this, that the author contrives to awaken in his reader an understanding of the diversity of civilizations. We are so accustomed to look from out our own culture without adjusting our prejudices, and to form judgments in a moment of time upon an almost eternal phenomenon. We take no account of the changes in culture, of the shifting perspectives, and alien outlook in countries which are spiritually as remote as another world. We condemn or praise with no real sympathy. In the hope of deepening understanding a few comparisons between civilizations are suggested in this article.The natural opposite of Europe has been always the East. But Roman Europe was, and modem Europe is, confronted by an Orient feverish and decadent. Syria and Egypt then can be compared to India now. We can find parallels between the local cults of those countries that rose to sudden prominence as fashions at Rome and those that do the same to-day; or between the atmosphere of the Trismegistists and that of the followers of Shankara. Between that period and the present the true East and true West were separated by the vigorous world of Arab culture, alien alike to its eastern and its western neighbours.
Dickens and Spirituallsm
Authors: Clayton Joseph 
Published: October 2007

Quite a number of books have been published lately containing, so the spiritualists declare, messages from another world. The reading of these books does not suggest that the ‘spirits or their messages are any livelier or more intelligent than they were nearly seventy years ago, when Charles Dickens came across them.In The Haunted House, a Christmas story written for All the Year Round, 1859, Dickens begins with the revelations provided by a travelling companion in a railway train. The journey was by night, and the fellow passenger, armed with a pencil and pocket-book, was perpetually listening and taking notes.‘I have passed the night—as indeed I pass the whole of my time now—in spiritual intercourse,’ explained the man—’ a goggle-eyed gentleman of a perplexed aspect’—in the cold light of morning.The messages had not been rapped on any table, but had been deciphered in the jolts and bumps of the carriage. (Many of us are familiar with the rhythmic utterance of railway engines.) The seance— ‘conference’ the goggle-eyed gentleman preferred to call it—began with the greeting :’ Evil communications corrupt good manners.’‘“Sound,” said I; “but, absolutely new?”’‘“New from spirits,” returned the gentleman.’ The last entry in the notebook was : ‘A bird in the hand is worth two in the Bosh.’‘“Truly I am of the same opinion,” said I; “ but shouldn’t it be Bush?”’‘“It came to me, Bosh,” returned the gentle... n , )> )
St. Peter, St. Paul and St. Thomas
Authors: McNabb Vincent 
Published: October 2007

The following extracts from the Summa Theologica of St. Thomas may be of interest and value to our readers. They are found in the Secunda Secundae.Question 33. Article 4.Whether a man is bound to correct his prelate.Obj. 2. A gloss on Gal. II, 11 : ‘/ withstood him to the face adds : as an equal. Therefore since a subject is not equal to his prelate, he ought not to correct him ........ I answer that a subject is not competent to administer to his prelate the correction which is an act of justice through the coercive nature of punishment.But the fraternal correction which is an act of charity is within the competency of everyone in respect of any person towards whom he is bound by charity, provided there be something in that person which requires correction.Now an act which proceeds from a habit or power extends to whatever is contained under the object of that power or habit. Thus vision extends to all things comprised in the object of sight. Since, however, a virtuous act needs to be moderated by due circumstances, it follows that when a subject corrects his prelate he ought to do so in a becoming manner; not with impudence and harshness, but with gentleness and respect. Hence the Apostle says (I Tim. v, 1), An ancient man rebuke not, but entreat as a father. Wherefore Dionysius finds fault with Demophilus, a monk (Ep. viii), for rebuking a priest with insolence by striking and turning him out of the church.
The Book of St. Catherine of Siena
Authors: Curtayne Alice 
Published: October 2007

The Church has produced much spiritual writing in the five and a half centuries which have elapsed since this extraordinary genius of the Middle Ages, this woman of strenuous action, left us the written expression of her contemplative life. She, and the friends who wrote it for her, always spoke of it simply as ‘The Book,’ and after five hundred and fifty years it may well retain the title, for it has lost none of its unique character in Christian literature. It was written under peculiarly arresting circumstances : dictated by a woman of thirty-one, while in ecstasy, to three or four members of her famous circle: Barduccio, Stephen, Neri, Tuscan youths of noble family, who were her ardent disciples, and Christopher, a Sienese notary. This is the Saint’s own description of her mental and bodily state when in ecstasy:. . . . the bodily powers alone departed, becoming united to Me through affection of Love. Then is the memory full of nought but Me; the understanding uplifted � to contemplate My truth as object; the will, that follows the understanding, loves and unites itself to what the eye of the understanding sees. These powers, being united and gathered together and immersed and inflamed in Me, the body loses its feeling, so that the seeing eye sees not, and the hearing ear hears not, and the tongue does not speak, except as the abundance of the heart will sometimes permit it for the alleviation of the heart and the praise and glory of My name.’
Convolvulus
Authors: Sedgwick R.L. 
Published: October 2007

The rain had fallen drearily From the grey sky,And past the wet trees heavily The wine-cart rumbled by.The goodman doffed his coloured cap At every shrine,And prayed to God that no mishap Might overtake his wine.But the ruts grew deeper as They crossed the lea :The cart struck fast, the goodman was Powerless to free.The sinking wheels and stumbling horse Whose piteous neighShook the damp woods and the pale gorse That fringed the tortuous way.It chanced Our Lady was the first To cross the burn :Said she, ‘Give me some wine, I thirst— I’ll help thee in return.’The goodman bowed, and looking up—‘Right willingly,’He said : ‘But Lady, I’ve no cup Or glass to offer thee.’She picked a flower in the grass,Shaped like a bowl,Which served her as a little glass Not as a buttonhole.Our Lady drank the wine, and lo!The cart was free.And once more on their way they go Praising God joyfully.The flower still blossoms in the grass: Folk call it thus,Either Our Lady’s little glass,Or wild convolvulus.R. L. Sedgwick.
Martyrs
Authors: Hill Philip Maurice 
Published: October 2007

‘Apellabo martyrem; praedicavi satis.’—St. Ambrose.With what emotion must he who travels from the south first break upon the Campagna, and see presently the Appian Way. Here, on the outskirts of the City, is the heart of Rome. Not the centre of her grandeur and dominion, not the seat of justice and power, but the cradle of Christianity suffering and victorious.‘Now—the single little turret that remains On the plains,By the caper over-rooted, by the gourd Overscored . . . .Here is ‘love among the ruins.’ But divine, not human, love. Along the line marked by the cypresses lie the catacombs, untouched by any pious transformation. These were the sleeping places of the martyrs. Who were they, and what have they done for Christianity?First, they have supplied certain proofs needful for the understanding of the nature and continuity of the Faith and of the Church.No cause was ever so hopeless as that of Christianity on the morning after the Crucifixion. No religion has ever won a wider dominion in a shorter time.The Holy Spirit prepared the soil for Christianity and made sure its growth and harvesting. The universal Empire of Pagan Rome forshadowed the Universal Church. It brought peace, order and unity of government to peoples as various in mind as in colour and race, and helped that ‘empire within the Empire’ to gather men of every condition and in all places under one rule of thought and life. Guided by the Church, religious licence was exchanged for spiritual liberty, and thousands embraced a creed which made all men equal before God.
Experimental Results
From Controlled Blade Tip/Shroud Rubs at Engine
Speed
Authors: Padova Corso , Barton Jeffery , Dunn Michael G. , Manwaring Steve 
Published: October 2007

Abstract
Experimental results obtained for an Inconel® compressor blade rubbing a steel casing at engine speed are described. Load cell, strain gauge, and accelerometer measurements are discussed and then applied to analyze the metal-on-metal interaction resulting from sudden incursions of varying severity, defined by incursion depths ranging from 13μm to 762μm (0.0005in. to 0.030in.). The results presented describe the transient dynamics of rotor and casing vibro-impact response at engine operational speed similar to those experienced in flight. Force components at the blade tip in axial and circumferential directions for a rub of moderate incursion depth (140μm) are compared to those for a severe rub (406μm). Similar general trends of variation during the metal-to-metal contact are observed. However, in the nearly threefold higher incursion the maximum incurred circumferential load increases significantly, while the maximum incurred axial load increases much less, demonstrating the non-linear nature of the rub phenomena. Concurrently, the stress magnification on the rubbing blade at root mid-chord, at tip leading edge, and at tip trailing edge is discussed. The results point to the possibility of failure occurring first at the airfoil trailing edge. Such a failure was in fact observed in the most severe rub obtained to date in the laboratory, consistent with field observations. Computational models to analyze the non-linear dynamic response of a rotating beam with periodic pulse loading at the free-end are currently under development and are noted.
High-Pressure Pocket
Damper Seals: Leakage Rates and Cavity
Pressures
Authors: Gamal Ahmed
M. , Ertas Bugra
H. , Vance John M. 
Published: October 2007

Abstract
The turbomachinery component of interest in this paper, the pocket damper seal, has the dual purpose of limiting leakage and providing an additional source of damping at the seal location. The rotordynamic coefficients of these seals (primarily the direct stiffness and damping) are highly dependent on the leakage rates through the seals and the pressures in the seals’ cavities. This paper presents both numerical predictions and experimentally obtained results for the leakage and the cavity pressures of pocket damper seals operating at high pressures. The seals were tested with air, at pressures up to 1000psi(6.92MPa), as the working fluid. Earlier flow-prediction models were modified and used to obtain theoretical reference values for both mass flow rates and pressures. Leakage and static pressure measurements on straight-through and diverging-clearance configurations of eight-bladed and twelve-bladed seals were used for code validation and for calculation of seal discharge coefficients. Higher than expected leakage rates were measured in the case of the twelve-bladed seal, while the leakage rates for the eight-bladed seals were predicted with reasonable accuracy. Differences in the axial pitch lengths of the cavities and the blade profiles of the seals are used to explain the discrepancy in the case of the twelve-bladed seal. The analysis code used also predicted the static cavity pressures reasonably well. Tests conducted on a six-bladed pocket damper seal to further investigate the effect of blade profile supported the results of the eight-bladed and twelve-bladed seal tests and matched theoretical predictions with satisfactory accuracy.