bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adventitia removal does not modify the α1D‐adrenoceptors response in aorta during hypertension and ageing
Authors: Gómez‐Zamudio J. H. , Villalobos‐Molina R. 
Published: June 2009

Summary1The aim of the current study was to characterize the α1‐adrenergic receptors (α1‐ARs) present in the isolated tunica media of aorta, in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats during the course of ageing and hypertension (rats of 1, 3, 6 and 12 months of age). In all vessels, endothelium was removed.2In isolated aortic rings, phenylephrine increased contraction in a concentration‐ and age‐dependent manner and was impaired in old SHR compared with WKY rats.3The α1‐AR selective antagonist prazosin showed high affinity (pA2) in vessels from both rat strains.4The potency of the α1A‐AR selective antagonists, RS 100329 (5‐methyl‐3‐[3‐[4‐[2‐(2,2,2,‐trifluoroethoxy) phenyl]‐1‐piperazinyl] propyl]‐2,4‐(1H)‐pyrimidinedione) and 5‐methylurapidil in antagonizing aortic phenylephrine‐responses was low.5The α1D‐AR selective antagonist, BMY 7378 (8‐[2‐[4‐(2‐methoxyphenyl)‐1 piperazynil] ethyl]‐8‐azaspiro [4.5] decane‐7,9‐dione) potently blocked phenylephrine‐induced responses in aorta from both strains and at all ages.6Adventitia removal decreasedEmaxin older rats and modified the relative affinity (pD2), but did not affect the affinity of the selective antagonists.7The results suggest that aorta tunica α1D‐AR is the main subtype involved in phenylephrine‐induced contraction of rat aorta, while α1A‐AR plays only a minor role.8Ageing and hypertension did not modify α1‐ARs in the blood vessel and the tunica adventitia does not seem to participate in contraction, even though α1‐ARs are expressed.
Mast cells, peptides and cardioprotection – an unlikely marriage?
Authors: Walsh S. K. , Kane K. A. , Wainwright C. L. 
Published: June 2009

Summary1 Mast cells have classically been regarded as the ‘bad guys’ in the setting of acute myocardial ischaemia, where their released contents are believed to contribute both to tissue injury and electrical disturbances resulting from ischaemia. Recent evidence suggests, however, that if mast cell degranulation occurs in advance of ischaemia onset, this may be cardioprotective by virtue of the depletion of mast cell contents that can no longer act as instruments of injury when the tissue becomes ischaemic.2 Many peptides, such as ET‐1, adrenomedullin, relaxin and atrial natriuretic peptide, have been demonstrated to be cardioprotective when given prior to the onset of myocardial ischaemia, although their physiological functions are varied and the mechanisms of their cardioprotective actions appear to be diverse and often ill defined. However, one common denominator that is emerging is the ability of these peptides to modulate mast cell degranulation, raising the possibility that peptide‐induced mast cell degranulation or stabilization may hold the key to a common mechanism of their cardioprotection.3 The aim of this review was to consolidate the evidence implying that mast cell degranulation could play both a detrimental and protective role in myocardial ischaemia, depending upon when it occurs, and that this may underlie the cardioprotective effects of a range of diverse peptides that exerts physiological effects within the cardiovascular system.
Long‐term changes in dynamic cerebral autoregulation: a 10 years follow up study
Authors: Brodie Fiona G. , Panerai Ronney B. , Foster Stephanie , Evans David H. , Robinson Thompson G. 
Published: June 2009

SummaryThis study takes a novel approach to describing time‐related changes in dynamic cerebral autoregulation (dCA). It is well‐recognized that dCA exhibits both intra‐ and inter‐ subject variability, and this study seeks to characterize the extent to which intra‐subject variability occurs after a significant period of time by studying the same subjects 10 years apart, thus eliminating inter‐subject variability as a source of error. Ten healthy subjects were identified in 1998 and followed up in 2008. On each visit they underwent simultaneous recordings of right middle cerebral artery cerebral blood flow velocity (RMCA CBFV), blood pressure and heart rate. Data were analysed in the frequency domain using transfer function analysis and in the time domain using CBFV step response, from which the autoregulatory index (ARI) was calculated. Ten subjects of mean age 35·5 (range 24–51) years in 1998 (seven male) were studied. There was a significant fall in ARI from 1998–2008 (ΔARI = 1·1, P = 0·021), along with a significant rise in coherence in 2008 (at 0·05 Hz, P = 0·018). Difference in mean step response between 1998 and 2008 was also significant (P = 0·045). This is the first study to assess dCA in the same subjects 10 years apart, providing a novel opportunity to assess intra‐subject variation in dCA after a long time period has elapsed. A fall in frequency and time domain parameters was observed. This is important, and needs to be considered in future studies assessing long‐term changes in dCA, particularly given the body evidence which suggests that dCA is unaffected by ageing.
Evaluation of endothelial function using finger plethysmography
Authors: Faizi A. K. , Kornmo D. W. , Agewall S. 
Published: June 2009

SummaryBackground:  The aims of this study were to establish the optimum duration of blood flow occlusion to obtain maximal response and to compare the response after lower‐arm and upper‐arm occlusion.Methods:  Pulse wave amplitude was analysed using a novel finger plethysmograph (EndoPat; Itamar). For measuring reactive hyperaemic index (RHI) induced by forearm cuff occlusion, 30 healthy subjects were examined at different days in a random order of four cuff occlusion times (1·5, 3, 5 and 8 min). RHI induced by 5 min upper‐arm cuff occlusion was also measured in 20 subjects.Results:  Average RHI was lower with 1·5 and 3 min forearm occlusion compared with 8 min forearm occlusion (P = 0·002 and P = 0·024). There was no significant difference between values of 5 min and 8 min forearm occlusion and between 5 min forearm and 5 min upper‐arm occlusion (P = 0·1). All subjects reported less discomfort after forearm occlusion compared with upper‐arm occlusion.Conclusion:  Maximum response was reached after 5 min of blood flow occlusion and therefore this occlusion time is recommended. The response after forearm and upper‐arm occlusion did not differ significantly. Forearm occlusion might be preferred as this caused less discomfort.
Influence of humic acid on water retention and nutrient acquisition in simulated golf putting greens
Authors: Van Dyke A. , Johnson P. G. , Grossl P. R. 
Published: June 2009

AbstractHumic substances are frequently applied to creeping bentgrass (Agrostis palustris Huds.) on golf putting greens to improve turf health and are marketed to enhance nutrient acquisition and possibly aid in retaining water in drought prone environments, but information on the role of humic substances in increasing soil water retention is limited. Additionally, it is difficult to separate the beneficial effects of nutrients and other ingredients added to commercial humic formulations from the effects of the pure humic substance. In our study, pure humic acid, tannic and citric acids were added to simulated creeping bentgrass putting greens. The organic acids were applied at normalized carbon rates of 250 mg C per litre by watering solutions through an automated irrigation system. Volumetric water content (VWC) and irrigation frequency, shoot and root growth, and tissue nutrient concentration of the turf were measured. None of the organic acid treatments improved water retention in the simulated greens. The humic acid‐treated greens required more frequent irrigation than the untreated greens indicating that they were drying out more quickly. In addition, the addition of humic acid did not result in an increased tissue concentration of nutrients in the creeping bentgrass, top growth or dry shoot mass compared with the other treatments. However, creeping bentgrass root length was greater in the greens treated with humic acid compared with the untreated control.
Aggregate stability in organically and conventionally farmed soils
Authors: Williams N. D. , Petticrew E. L. 
Published: June 2009

AbstractA range of factors that influence aggregate stability and soil erodibility were analysed for soils sampled from land managed under contrasting agricultural methods. These included: an organic farm; a conventional farm that incorporated organic fertilizers; a conventional farm that only used inorganic fertilizers; and a non‐cultivated control site. The stability of aggregates that compose the bulk soil structure (macroaggregates), and aggregates that were mobilized from the soil by simulated rainfall and surface runoff (microaggregates), were evaluated in terms of the soil fragmentation fractal dimension, organic carbon content and ATP (adenosine 5′‐triphosphate; a signature of live biomass) concentration. The results were used to interpret the existing physical condition of the soils, the (microbial) processes that contribute to that physical structure, and how both pedogenic processes and existing soil quality are influenced by agricultural methods. The soils sampled for this study were demonstrated to be multi‐fractal in nature: soils with greater bulk density were composed of more stable macro‐aggregates, which, in turn, fragmented into larger, more stable micro‐aggregates, rendering the entire soil structure less erodible. Soil erodibility and sustainable soil management should therefore be approached at multiple scales. The primary control on both macro‐ and micro‐aggregate stability was determined to be the organic matter input to the soil, as represented by measurements of organic carbon and ATP. Organic content was greatest for the non‐cultivated soil, which reflects the degradation of organic reserves in cultivated soils. For cultivated soils, it was not possible to differentiate aggregate stability for soils managed under organic or conventional (i.e. using biological and inorganic fertilizers) farming practices, but aggregates of soils that only received artificial fertilizers consistently exhibited less stability.
Integer linear programming for a cutting problem in the wood‐processing industry: a case study
Authors: Koch Sören , König Sebastian , Wäscher Gerhard 
Published: June 2009

AbstractIn this paper, the authors present a case study from the wood‐processing industry. It focuses on a cutting process in which material from stock is cut down in order to provide the items required by the customers in the desired qualities, sizes, and quantities. In particular, two aspects make this cutting process special. Firstly, the cutting process is strongly interdependent, with a preceding handling process, which, consequently, cannot be planned independently. Secondly, if the trim loss is of a certain minimum size, it can be returned into stock and used as input to subsequent cutting processes. In order to reduce the cost of the cutting process, a decision support tool has been developed that incorporates an integer linear programming model as a central feature. The model is described in detail, and experience from the application of the tool is reported.
The long‐term development of organised business and its implications for corporatism: A cross‐national comparison of membership, activities and governing capacities of business interest associations, 1980–2003
Authors: TRAXLER FRANZ 
Published: June 2009

AbstractInternationalisation of markets and the demise of Keynesianism have made business more independent of associational action. Membership density and ‘corporatist’ involvement in wage bargaining and public policy have declined only modestly, while the capacity to govern members has dwindled significantly. This development is driven by the way in which large firms and the state relate to business associations. Large firms still have a vital interest not only in associational action, but also in integrating their smaller counterparts. Stated‐based support for multi‐employer bargaining, as established in most countries, buttresses business associations. By equipping the associations with an encompassing grip on the labour market, this support prompts governments to involve them in public policy. Since encompassing labour market regulation enables the associations to impose negative externalities on unaffiliated businesses, it provides them with a strong selective incentive for membership. The significant decline of the associations' governing capacity emanates from pressures of their large members to reduce costs of association. The implications of this development for interest intermediation are twofold. Given the strong decay of union power, the resilience of corporatism strongly hinges on the continued strength of organised business and on its state‐sponsored engagement in bargaining. At the same time, leeway for compromising has been restrained by the significant decline in the governing capacity of organised business. This decline echoes an ever‐growing predominance of large firms in business associations, while economic internationalisation exacerbates interest conflicts between larger and smaller firms. To the extent that this configuration of interest and power weakens the ability of business associations to integrate the mass of small firms, it develops into the new Achilles heel of corporatism.
Constitutive activity of cannabinoid‐2 (CB2) receptors plays an essential role in the protean agonism of (+)AM1241 and L768242
Authors: Mancini I , Brusa R , Quadrato G , Foglia C , Scandroglio P , Silverman LS , Tulshian D , Reggiani A , Beltramo M 
Published: June 2009

Background and purpose: Cannabinoid‐2 (CB2) receptor‐selective agonists have shown anti‐nociceptive activity in models of neuropathic and inflammatory pain, and the two agonists most widely used, (+/−)AM1241 [(2‐iodo‐5‐nitrophenyl)‐[1‐(1‐methylpiperidin‐2‐ylmethyl)‐1H‐indol‐3‐yl‐methanone] and L768242 [(2,3‐dichloro‐phenyl)‐[5‐methoxy‐2‐methyl‐3‐(2‐morpholin‐4‐yl‐ethyl)‐indol‐1‐yl]‐methanone] (GW405833), have been suggested to be protean agonists. Here we investigated the role of the constitutive activity of CB2receptors in (+)AM1241 and L768242 protean agonism.Experimental approach: Pharmacological profiles of CB2receptor ligands were evaluated in Chinese hamster ovary cells expressing recombinant human (hCB2) or rat (rCB2) receptors, by measuring modulation of cAMP. To assess the influence of constitutive activity on pharmacological profile, constitutive activity was abolished by pretreatment with AM630 [(6‐iodo‐2‐methyl‐1‐[2‐(4‐morpholinyl)ethyl]‐1H‐indol‐3‐yl](4‐methoxyphenyl) methanone)], followed by extensive washing.Key results: In cell lines expressing either hCB2or rCB2receptors, (+)AM1241 did not reverse forskolin stimulation of cAMP levels. Conversely, L768242 was an inverse agonist at both hCB2and rCB2receptors. Abolition of constitutive activity disclosed (+)AM1241 and L768242 agonist activity, while activity of CP55940 [5‐(1,1‐dimethylheptyl)‐2‐[(1R,2R,5R)‐5‐hydroxy‐2‐(3‐hydroxy‐propyl)‐cyclohexyl]‐phenol] was unaffected and AM630 became a neutral antagonist. In presence of constitutively active CB2receptors, (+)AM1241 antagonized CP55940, but when constitutive activity was abolished, it acted as a partial agonist with additive or antagonistic behaviour, depending on concentration.Conclusions and implications: These results show that (+)AM1241 and L768242 are protean agonists at both hCB2and rCB2receptors. Abolition of constitutive activity reveals the agonist activity of these compounds. Thus, differences betweenin vivoandin vitroprofiles of CB2receptor agonists could be due to different levels of constitutive activity in recombinant versus native CB2receptors.
Bovine glycomacropeptide induces cytokine production in human monocytes through the stimulation of the MAPK and the NF‐κB signal transduction pathways
Authors: Requena Pilar , Daddaoua Abdelali , Guadix Emilia , Zarzuelo Antonio , Suárez María Dolores , De Medina Fermín Sánchez , Martínez‐Augustin Olga 
Published: June 2009

Background and purpose:  Bovine glycomacropeptide (BGMP) is a natural milk peptide that is produced naturally in the gastrointestinal tract during digestion. Glycomacropepide has intestinal anti‐inflammatory activity, but the mechanism of action is unknown. Here we have characterized the effects of BGMP on monocytes.Experimental approach:  We have used human THP‐1 cells as an in vitro monocyte model. The effect of BGMP on the secretion of tumour necrosis factor (TNF), interleukin (IL)‐1β and IL‐8 was assessed, as well as the involvement of the NF‐κB and MAP kinase signalling pathways. The stimulatory effect of BGMP was also tested in human peripheral blood monocytes.Key results:  BGMP up‐regulated the secretion of TNF, IL‐1β and IL‐8 in a concentration‐dependent fashion. The biological activity was exerted by the intact peptide, because cytokine secretion was not affected by protease inhibitors. The secretion of IL‐8 and specially TNF and IL‐1β was blocked by PD98059, SP600125, SB203580 and Bay11‐7082, suggesting the involvement of the MAP kinases p38, c‐Jun N‐terminal kinase and ERK and particularly the NF‐κB pathway, although IL‐8 secretion was independent of p38. BGMP was shown to elicit the phosphorylation of IκB‐α and the nuclear translocation of the NF‐κB subunits p50 and p65. The effect of BGMP on cytokine secretion was validated in human primary blood monocytes.Conclusions and implications:  BGMP stimulates human monocytes, operating via MAP kinase and NF‐κB pathways. BGMP may exert an indirect intestinal anti‐inflammatory effect by potentiating host defences against invading microorganisms.
Mammalian P2X7 receptor pharmacology: comparison of recombinant mouse, rat and human P2X7 receptors
Authors: Donnelly‐Roberts Diana L , Namovic Marian T , Han Ping , Jarvis Michael F 
Published: June 2009

Background and purpose: Acute activation of P2X7 receptors rapidly opens a non‐selective cation channel. Sustained P2X7 receptor activation leads to the formation of cytolytic pores, mediated by downstream recruitment of hemichannels to the cell surface. Species‐ and single‐nucleotide polymorphism‐mediated differences in P2X7 receptor activation have been reported that complicate understanding of the physiological role of P2X7 receptors. Studies were conducted to determine pharmacological differences between human, rat and mouse P2X7 receptors.Experimental approach: Receptor‐mediated changes in calcium influx and Yo‐Pro uptake were compared between recombinant mouse, rat and human P2X7 receptors. For mouse P2X7 receptors, wild‐type (BALB/c) and a reported loss of function (C57BL/6) P2X7 receptor were also compared.Key results: BzATP [2,3‐O‐(4‐benzoylbenzoyl)‐ATP] was more potent than ATP in stimulating calcium influx and Yo‐Pro uptake at rat, human, BALB/c and C57BL/6 mouse P2X7 receptors. Two selective P2X7 receptor antagonists, A‐740003 and A‐438079, potently blocked P2X7 receptor activation across mammalian species. Several reported P2X1 receptor antagonists [e.g. MRS 2159 (4‐[(4‐formyl‐5‐hydroxy‐6‐methyl‐3‐[(phosphonooxy)methyl}‐2‐pyridinyl)azo]‐benzoic acid), PPNDS and NF279] blocked P2X7 receptors. NF279 fully blocked human P2X7 receptors, but only partially blocked BALB/c P2X7 receptors and was inactive at C57BL/6 P2X7 receptors.Conclusions and implications: These data provide new insights into P2X7 receptor antagonist pharmacology across mammalian species. P2X7 receptor pharmacology in a widely used knockout background mouse strain (C57BL/6) was similar to wild‐type mouse P2X7 receptors. Several structurally novel, selective and competitive P2X7 receptor antagonists show less species differences compared with earlier non‐selective antagonists.
Agonist‐specific patterns of β2‐adrenoceptor responses in human airway cells during prolonged exposure
Authors: Düringer Caroline , Grundström Gunilla , Gürcan Eylem , Dainty Ian A , Lawson Mandy , Korn Solange H , Jerre Anders , Håkansson Hanna Falk , Wieslander Elisabet , Fredriksson Karin , Sköld Carl Magnus , Löfdahl Magnus , Löfdahl Claes‐Göran , Nicholls David J , Silberstein David S 
Published: June 2009

Background and purpose:  β2‐Adrenoceptor agonists (β2‐agonists) are important bronchodilators used in the treatment of asthma and chronic obstructive pulmonary disease. At the molecular level, β2‐adrenergic agonist stimulation induces desensitization of the β2‐adrenoceptor. In this study, we have examined the relationships between initial effect and subsequent reduction of responsiveness to restimulation for a panel of β2‐agonists in cellular and in vitro tissue models.Experimental approach:  β2‐Adrenoceptor‐induced responses and subsequent loss of receptor responsiveness were studied in primary human airway smooth muscle cells and bronchial epithelial cells by measuring cAMP production. Receptor responsiveness was compared at equi‐effective concentrations, either after continuous incubation for 24 h or after a 1 h pulse exposure followed by a 23 h washout. Key findings were confirmed in guinea pig tracheal preparations in vitro.Key results:  There were differences in the reduction of receptor responsiveness in human airway cells and in vitro guinea pig trachea by a panel of β2‐agonists. When restimulation occurred immediately after continuous incubation, loss of responsiveness correlated with initial effect for all agonists. After the 1 h pulse exposure, differences between agonists emerged, for example isoprenaline and formoterol induced the least reduction of responsiveness. High lipophilicity was, to some extent, predictive of loss of responsiveness, but other factors appeared to be involved in determining the relationships between effect and subsequent loss of responsiveness for individual agonists.Conclusions and implications:  There were clear differences in the ability of different β2 agonists to induce loss of receptor responsiveness at equi‐effective concentrations.
Functional evidence for the expression of P2X1, P2X4 and P2X7 receptors in human lung mast cells
Authors: Wareham K , Vial C , Wykes RCE , Bradding P , Seward EP 
Published: June 2009

Background and purpose: P2X receptors are widely expressed in cells of the immune system with varying functions. This study sought to characterize P2X receptor expression in the LAD2 human mast cell line and human lung mast cells (HLMCs).Experimental approach: Reverse transcriptase polymerase chain reaction (RT‐PCR) and patch clamp studies were used to characterize P2X expression in mast cells using a range of pharmacological tools.Key results: RT‐PCR revealed P2X1, P2X4 and P2X7 transcripts in both cell types; mRNA for P2X6 was also detected in LAD2 cells. Under whole‐cell patch clamp conditions, rapid application of ATP (1–1000 µM) to cells clamped at −60 mV consistently evoked inward currents in both types of cells. Brief application of ATP (1 s) evoked a rapidly desensitizing P2X1‐like current in both cell types. This current was also elicited by αβmethylene ATP (10 µM, 94% cells,n= 31) and was antagonized in LAD2 cells by NF 449 (1 µM) and pyridoxal phosphate‐6‐azo(benzene‐2,4‐disulphonic acid) (1–10 µM). A P2X7‐like non‐desensitizing current in response to high concentrations of ATP (1–5 mM) was also seen in both cell types (96% LAD2,n= 24; 54% HLMCs,n= 24) which was antagonized by AZ11645373 (1 µM). P2X7‐like responses were also evoked in LAD2 cells by 2′(3′)‐0‐(4‐benzoylbenzoyl)ATP (300 µM). A P2X4‐like current was evoked by 100 µM ATP (80% LAD2,n= 10; 21% HLMCs,n= 29), the amplitude and duration of which was potentiated by ivermectin (3 µM).Conclusion and implications: Our data confirmed the presence of functional P2X1, P2X4 and P2X7 receptors in LAD2 cells and HLMCs.