bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical properties of recycled polyethylene ecocomposites filled with natural organic fillers
Authors: La Mantia F.P. , Morreale M.
Published: July 2006

The use of natural organic fillers in addition to postconsumer recycled polymers is getting a growing interest during the last years; this is due to many advantages they can provide in terms of cost, aesthetic properties, environmental impact. In this work, several types of wood flour (differing each other with regard to production source and particle size) were added to a recycled polyethylene coming from films for greenhouses and the effects of filler type, content, and size were investigated. Investigation was then focused on the improvement of mechanical properties, through the addition of polar copolymers (ethylene‐co‐acrylic acid, ethylene‐vinyl acetate) and a maleic anhydride‐grafted‐grafted polyethylene (Licocene® PE MA 4351 TP), in order to try to overcome the poor adhesion between polar filler particles and nonpolar polymer chains. Investigation was also based on SEM micrographs. An overall positive influence of these additives was observed. Polym. Eng. Sci. 46:1131–1139, 2006. © 2006 Society of Plastics Engineers.
Biaxial orientation in LLDPE films: Comparison of infrared spectroscopy, X‐ray pole figures, and birefringence techniques
Authors: Ajji A. , Zhang X. , Elkoun S.
Published: July 2006

In this study, linear low‐density polyethylene films were produced using different processes (film blowing and biaxial orientation) and processing conditions. The orientation of the films was characterized in terms of their biaxial crystalline, amorphous, and global orientation factors using birefringence, tilted incidence polarized Fourier Transform Infrared Spectroscopy (FTIR), and X‐ray diffraction pole figures. Evaluation of a simplified FTIR procedure without the use of the tilted method for the determination of crystalline orientation factors proposed in the literature is also evaluated and assessed. The results indicate that FTIR overestimate the crystalline orientation factors, particularly for the crystalline a‐axis. Significant discrepancies are also observed for the b‐axis orientation, which may be due to an overlap of the amorphous phase contribution. Those differences are larger for films with low orientation, such as blown films. Amorphous phase orientation from FTIR depends on the band used and is not necessarily in agreement with that determined from the combination of X‐ray and birefringence. The simplified FTIR procedure is proven to be inadequate in the case of linear low‐density polyethylene blown films studied having a random lamellar crystalline morphology. POLYM. ENG. SCI. 46:1182–1189, 2006. © 2006 Society of Plastics Engineers.
Dependence of elastic properties and ultrasonic velocities on the structure of vanadate lead tellurite glasses
Authors: Palanivelu N. , Rajendran V.
Published: July 2006

The structure and stability of ternary tellurite (50 – x ) V2O5–x PbO–50TeO2 glasses have been investigated by means of ultrasonic studies. Ultrasonic velocities and attenuation measurements have been made over a wide range of temperatures from 150 to 480 K at 5 MHz. At room temperature, a gradual increase in density and a decrease in velocities and Debye temperature with increase in PbO content have been observed. A change in the trend of variation in T g, elastic moduli and attenuation with an increase in PbO content has been noticed at 20 wt% of PbO. These results reveal a change in the Te co‐ordination from trigonal bipyramid to trigonal pyramid, with the formation of ionic bonds due to the addition of PbO. In addition, the breaking of more Te–O–Te and Te–O–Pb linkages, leaving non‐bridging oxygen with increasing in PbO content, is known to occur in these glasses. The temperature dependence of the parameters investigated has been explained in terms of the weakening of the structure, which is due to the instability of the TeO4 trigonal bipyramid unit with increasing temperature. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantitative Structure–Activity Relationship Studies for the Binding Affinities of Imidazobenzodiazepines for the α6 Benzodiazepine Receptor Isoform Utilizing Optimized Blockwise Variable Combination by Particle Swarm Optimization for Partial Least Squares Modeling
Authors: Hu Leqian , Wu Hailong , Lin Weiqi , Jiang Jianhui , Yu Ruqin
Published: July 2006

Binding affinities of a series of substituted imidazobenzodiazepines for the α6 Benzodiazepine Receptor (BzR) isoform are investigated by the Optimized Blockwise Variable Combination (OBVC) by Particle Swarm Optimization (PSO) based on Partial Least Squares (PLS) modeling. The QSAR analysis result showed that MolRef, AlogP, MRCM**‐3, Rotatable bonds (Rotlbonds), Hydrogen Bond Acceptors (Hbond acceptor), five Jurs descriptors, two Shadow indices descriptors and principal moment of inertia are the most important descriptors among all the investigated descriptors. One can change the molar refractivity, the polar interactions between molecules, the shape of the molecules, the principal moments of inertia about the principal axes of a molecule, the hydrophobic character of the molecule, the number of Rotlbonds and Hbond acceptors of the compounds to adjust the binding affinities of imidazobenzodiazepine for the α6 BzR isoform. The Quantitative Structure–Activity Relationship (QSAR) analysis result was also compared with MLR, PLS, and hierarchical PLS algorithms. It has been demonstrated that OBVC by PSO for PLS modeling shows satisfactory performance in the QSAR analysis.
Treatments with losartan or enalapril are equally sensitive to deterioration in renal function from cyclooxygenase inhibition
Authors: Juhlin Tord , Erhardt Leif R. , Ottosson Helene , Jönsson Bo A.G. , Höglund Peter
Published: July 2006

Background

The beneficial effects of angiotensin converting enzyme (ACE)‐inhibitors are in part mediated through the inhibition of the degradation of the vasodilator bradykinin. The bradykinin effect is counteracted by cyclooxygenase‐inhibitors. Angiotensin receptor blockers (ARBs) do not affect bradykinin.

Aims

To test the hypothesis that renal counteraction from a cyclooxygenase‐inhibitor, diclofenac, is different in subjects treated with an ACE‐inhibitor, enalapril compared with an ARB, losartan.

Methods

Twelve elderly, healthy, slightly over‐hydrated subjects received diclofenac orally after pre‐treatment with a diuretic, bendroflumethiazide, and enalapril or bendroflumethiazide and losartan, in a double‐blind cross‐over fashion, with a wash‐out period of at least 1 week.

Results

Diclofenac reduced GFR significantly from 81(64–98) ml/min at first observations after dose for enalapril to 29(16–42) and from 76(64–88) after losartan to 35(24–46). There was no significant difference between enalapril and losartan in GFR. Diclofenac induced decreases in urine flow, excretion rates and clearances of sodium, osmolality clearance and free water clearance, irrespective of treatment with enalapril or losartan. However, serum potassium and handling of potassium were significantly lower after losartan‐treatment.

Conclusion

The negative renal effects of diclofenac administration in subjects with activation of the renin–angiotensin system and enalapril treatment are the same in subjects with activation of the renin–angiotensin system and losartan treatment.
Some aspects of the venom proteome of the Colubridae snake Philodryas olfersii revealed from a Duvernoy's (venom) gland transcriptome
Authors: Ching Ana T.C. , Rocha Marisa M.T. , Paes Leme Adriana F. , Pimenta Daniel C. , de Fátima D. Furtado Maria , Serrano Solange M.T. , Ho Paulo L. , Junqueira-de-Azevedo Inácio L.M.
Published: July 2006

We investigated the putative toxins of Philodryas olfersii (Colubridae), a representative of a family of snakes neglected in venom studies despite their growing medical importance. Transcriptomic data of the venom gland complemented by proteomic analysis of the gland secretion revealed the presence of major toxin classes from the Viperidae family, including serine proteases, metalloproteases, C‐type lectins, Crisps, and a C‐type natriuretic peptide (CNP). Interestingly, the phylogenetic analysis of the CNP precursor showed it as a linker between two related precursors found in Viperidae and Elapidae snakes. We suggest that these precursors constitute a monophyletic group derived from the vertebrate CNPs.
Hyperosmotic stress‐dependent NFκB activation is regulated by reactive oxygen species and IGF‐1 in cultured cardiomyocytes
Authors: Eisner Verónica , Criollo Alfredo , Quiroga Clara , Olea-Azar Claudio , Santibañez Juan Francisco , Troncoso Rodrigo , Chiong Mario , Díaz-Araya Guillermo , Foncea Rocío , Lavandero Sergio
Published: July 2006

We have recently shown that hyperosmotic stress activates p65/RelB NFκB in cultured cardiomyocytes with dichotomic actions on caspase activation and cell death. It remains unexplored how NFκB is regulated in cultured rat cardiomyocytes exposed to hyperosmotic stress. We study here: (a) if hyperosmotic stress triggers reactive oxygen species (ROS) generation and in turn whether they regulate NFκB and (b) if insulin‐like growth factor‐1 (IGF‐1) modulates ROS production and NFκB activation in hyperosmotically‐stressed cardiomyocytes. The results showed that hyperosmotic stress generated ROS in cultured cardiac myocytes, in particular the hydroxyl and superoxide species, which were inhibited by N‐acetylcysteine (NAC). Hyperosmotic stress‐induced NFκB activation as determined by IκBα degradation and NFκB DNA binding. NFκB activation and procaspase‐3 and ‐9 fragmentation were prevented by NAC and IGF‐1. However, this growth factor did not decrease ROS generation induced by hyperosmotic stress, suggesting that its actions over NFκB and caspase activation may be due to modulation of events downstream of ROS generation. We conclude that hyperosmotic stress induces ROS, which in turn activates NFκB and caspases. IGF‐1 prevents NFκB activation by a ROS‐independent mechanism.
Segmentation in the Pre-Industrial Labour Market: Women's Work in the Dutch Textile Industry, 1581–1810
Authors: van Nederveen Meerkerk Elise
Published: July 2006

This article analyses women's work in the Dutch textile industry in the seventeenth and eighteenth centuries within the framework of dual (or segmented) labour market theory. This theoretical framework is usually applied to the modern labour market, but it is also valuable for historical research. It clarifies, for example, how segmentation in the labour market influenced men's and women's work in the textile industry. Applying this analysis, we find that, even in periods without explicit gender conflict, patriarchal and capitalist forces utilized the gender segmentation of the labour market to redefine job status and labour relations in periods of economic change. Although this could harm the economic position of all women and migrants, it appears that single women were affected most by these mechanisms.
Globalizing the Harlem Renaissance: Irish, Mexican, and ‘Negro’ renaissances in The Survey, 1919–1929
Authors: Johnson Bob
Published: July 2006

This essay situates the Harlem Renaissance in a world-historical context by building on the global perspective offered by the architect of that renaissance, Alain Locke. It demonstrates that contemporaries like Locke saw the Harlem Renaissance to be a local episode in a broader phenomenon of racial and national renaissance that included post-war developments in Ireland and Mexico. The core argument is that American progressives found in these renaissances three distinct models for defining the proper relationship between race and nation: in the Irish case, a racially homogeneous nation-state premised on a repudiation of the colonizer and his culture; in the Mexican case, a syncretic nation-state based on the cultural and biological fusion of the colonizer and colonized; and in the Harlem case, a pluralist nationstate that held in balance otherwise relatively autonomous races.
Global rust belt: Hemileia vastatrix and the ecological integration of world coffee production since 1850
Authors: McCook Stuart
Published: July 2006

The quantitative growth of coffee production and consumption in the nineteenth and twentieth centuries produced qualitative transformations along every step of the coffee commodity chain. The economic integration of the global coffee market in this period triggered major east-west biological exchanges between the world's coffee regions. The global epidemic of coffee leaf rust, caused by the fungus Hemileia vastatrix, illustrates the ecological and economic impact of such exchanges. Between 1865 and 1985, the epidemic spread from its original focus in Ceylon to engulf all of the world's coffee zones. Its economic impact varied considerably: in some places it destroyed more than 90% of the coffee crop, while in others it was little more than a minor irritant. The epidemic's origins, its diffusion, and its impacts were not accidental, but reflected specific conjunctures of local and global biological and historical processes.
‘Trust in God, but tie your camel first.’ The economic organization of the trans-Saharan slave trade between the fourteenth and nineteenth centuries
Authors: Prange Sebastian
Published: July 2006

This article examines the economic organization of the trans-Saharan slave trade between the fourteenth and nineteenth centuries on those routes that moved slaves from Sudanic Africa via entrepôts in the Sahel and Sahara to the Maghrib. The commercial framework of this trade was integrated into ethnic, cultural, and religious systems, yet for its efficient operation could not rely solely on these social institutions. Temporary cooperation of itinerant slave traders is considered and then projected onto the broader patterns of commercial organization. It is shown that similar pressures resulted in comparable outcomes: partnerships were formed to take advantage of economies of scale in commercial services and to limit cooperation problems. This demonstrates that the organization of the trans-Saharan slave trade was economically rational and can be analysed in terms of cooperative and non-cooperative strategies. Moreover, it is argued that the trade was not restrained by social institutions but versatile in adapting its economic institutions to specific market imperfections. It is concluded that recent economic models are more useful in explaining the economic behaviour of slave traders than conventional neoclassical economics.
Britain, industry and perceptions of China: Matthew Boulton, ‘useful knowledge’ and the Macartney Embassy to China 1792–94
Authors: Berg Maxine
Published: July 2006

Global history has debated the emergence of a divergence in economic growth between China and the West during the eighteenth century. The Macartney Embassy, 1792–94, the first British embassy to China, occurring as it did at the end of the eighteenth century, was an event which revealed changing perceptions of China and the Chinese by different British interest groups from government, trade, industry and enlightened opinion. Many histories of the embassy recount failures of diplomacy and cultural misconception, or divergent ideas of science. This article examines attitudes of British industry to the embassy through the part played in its preparations by the Birmingham industrialist, Matthew Boulton, and revealed in correspondence in the Matthew Boulton Papers. The article uncovers debate among different interest groups over the objects and skilled personnel to be taken on the embassy. Were the objects purveyors of trade or tribute, or of ‘useful knowledge’ and ‘industrial enlightenment’?
Living standards in the past: new perspectives on well-being in Asia and Europe By Robert C. Allen, Tommy Bengtsson and Martin Dribe, eds. Oxford: Oxford University Press, 2005. Pp. xxii + 472. ISBN 0-19-928068-1
Authors: Booth Anne
Published: July 2006

We live in an age of increasingly abundant statistical information. The advent of more large data sets obtained from household surveys, as well as from population censuses, labour force surveys, economic censuses and so on, has facilitated reasonably accurate estimates of income and expenditures for households in many parts of the world. These estimates can in turn be used to estimate a number of distributional indicators, as well as estimates of relative and absolute poverty. In addition better census coverage has permitted estimates of infant and child mortality rates, life expectancies, literacy rates and indicators of educational attainment. Such data have in turn been used to estimate composite indicators of wellbeing such as the Human Development Index, not just for entire countries but often for regions within countries as well.
Moderatorvariablen für den Zusammenhang zwischen Commitment und transformationaler Führung
Authors: Pundt Alexander , Böhme Hendryk , Schyns Birgit
Published: July 2006

Zusammenfassung. Der Einfluss transformationaler Führung auf die affektive Bindung der Mitarbeiter an das Unternehmen wurde bereits in mehreren empirischen Untersuchungen nachgewiesen. Da die gefundenen Zusammenhänge jedoch eine erhebliche Streuung aufweisen, wird in vorliegender Untersuchung die Frage nach relevanten Moderatorvariablen gestellt. In einem ersten Schritt wurden aus theoretischen Überlegungen und bereits vorliegenden Befunden die zu erwartende Moderatorwirkung der Interaktionsdistanz sowie der Kommunikationsqualität abgeleitet. Zur Prüfung der aufgestellten Hypothesen wurden zwei Studien durchgeführt. Die Ergebnisse der ersten Studie (N = 155) legen nahe, dass der Zusammenhang zwischen transformationaler Führung und affektivem Commitment stärker ist, wenn Führungskraft und Mitarbeiter häufig in direktem Kontakt zueinander stehen. Die Ergebnisse der zweiten Studie (N = 538) zeigen diese Interaktionswirkung nicht. Allerdings konnte in Studie 2 gezeigt werden, dass der Zusammenhang zwischen transformationaler Führung und affektivem Commitment umso stärker ist, je höher die Qualität der Kommunikation zwischen Führungskraft und Mitarbeiter ist.
Haupt- und Moderatoreffekte der affektiven Organisationsbindung in der Belastungs-Beanspruchungs-Beziehung
Authors: Schmidt Klaus-Helmut
Published: July 2006

Zusammenfassung. In den letzten Jahren ist ein wachsendes Interesse an den Beziehungen der affektiven Organisationsbindung von Mitarbeitern mit deren Arbeitsbeanspruchung und Wohlbefinden zu beobachten. Neben Haupteffekten auf diese Konsequenzen haben zwei konkurrierende Hypothesen auch Moderatoreffekte des Commitment auf den Zusammenhang zwischen Arbeitsbelastungen und Beanspruchungs- bzw. Befindensmaßen angenommen. Die erste Hypothese geht davon aus, dass das Commitment die adversen Beanspruchungswirkungen zunehmender Arbeitsbelastungen verstärkt. Nach der zweiten Hypothese sollte das Commitment eine Pufferfunktion in der Belastungs-Beanspruchungs-Beziehung ausüben. Die bei 349 Altenpflegekräften erhobenen Daten belegen signifikante Haupteffekte des Commitment auf alle berücksichtigten Kriteriumsvariablen, mit positiven Vorzeichen für die Arbeitszufriedenheit und die Burnout-Dimension der persönlichen Erfüllung, sowie negativen Vorzeichen für die emotionale Erschöpfung und Depersonalisation. Die Ergebnisse stützen darüber hinaus auch die Pufferhypothese. Die Wirkungen hoher Arbeitsbelastungen auf die Arbeitszufriedenheit, Erschöpfung und Depersonalisation schwächen sich mit zunehmendem Commitment ab. Lediglich in der persönlichen Erfüllung verfehlte diese Wechselwirkung statistische Bedeutsamkeit. Die Ergebnisse weisen darauf hin, dass die Pufferfunktion des Commitment im Wesentlichen auf belastungsabhängigen Bewertungsprozessen beruht.
Tests und Tools
Authors: Trapmann Sabrina
Published: July 2006

Zusammenfassung. Vorgestellt wird die revidierte Form des Allgemeinen Interessen-Struktur-Tests (AIST-R) und des Umwelt-Struktur-Tests (UST-R). Das Verfahren basiert auf dem hexagonalen Interessenmodell von John Holland und ermöglicht die Messung von Interessen einer Person und Eigenschaften beruflicher Umwelten auf sechs Dimensionen. Im Vergleich zur Erstauflage des Verfahrens wurde fast die Hälfte der Items verändert, was die Verständlichkeit fördern und zur Berücksichtigung neuerer Berufsfelder führen soll. Der AIST-R/UST-R ist ein ökonomisch durchzuführendes und gut zu interpretierendes Verfahren, dessen Anwendungsbereich vor allem bei Berufs- und Laufbahnentscheidungen sowie in der Forschung gesehen wird. Der AIST-R wurde anhand eines verwandten Verfahrens, eines Persönlichkeitsverfahrens und an Schulnoten validiert. Inwieweit sich die revidierte Form des AIST auch als valide für z. B. berufliche Kriterien erweist, werden erst weitere Studien klären können. Für die Validität des UST-R und der Konsistenz- und Kongruenzannahmen liegen bislang nur Untersuchungen mit der unrevidierten Form vor.
Brain-Electrical Correlates of Negative Location Priming Under Sustained and Transient Attentional Context Conditions
Authors: Ruge Hannes , Naumann Ewald
Published: July 2006

In the present study event-related potentials (ERPs) and event-related lateralizations (ERLs) were analyzed to investigate mechanisms of attentional inhibition engaged when a target stimulus has to be located within a simultaneous target-distractor display. The putative after-effects of inhibition were examined with a prime-probe technique by comparing a “DT” condition (the prime Distractor location becomes the probe Target location) with a control condition (the probe target appears at a previously empty position). The specific aim was to dissociate more “automatic” aspects from more “controlled” aspects associated with the inhibition of distractor locations. To do so, we compared physically identical prime-probe pairs in a sustained-attention context (same target throughout a block) and a transient-attention context (trial-by-trial target specification). Three early ERP/ERL components showed differential effects for DT compared to control: (1) the posterior N1 with a diminished amplitude contralateral to the visual half-field side of target presentation, (2) the N2pc with an enhanced amplitude contralateral to the visual half-field side of target presentation, and (3) the posteriorly distributed N2 with a nonlateralized enhancement for DT compared to control. These effects were differently affected by the context manipulation. While the N2pc effect was observed exclusively under sustained attention, the N1 lateralization effect and the N2 effect were not differentially modulated. The N1 lateralization effect seems consistent with an inhibition-of-return explanation. The N2pc and N2 effects are supposed to be reflecting different aspects of a biased-competition model of distractor inhibition.
The Level of Reaction Time Determines the ERP Correlates of Auditory Negative Priming
Authors: Mayr Susanne , Niedeggen Michael , Buchner Axel , Orgs Guido
Published: July 2006

Responding to a stimulus that had to be ignored previously is usually slowed-down (negative priming effect). This study investigates the reaction time and ERP effects of the negative priming phenomenon in the auditory domain. Thirty participants had to categorize sounds as musical instruments or animal voices. Reaction times were slowed-down in the negative priming condition relative to two control conditions. This effect was stronger for slow reactions (above intraindividual median) than for fast reactions (below intraindividual median). ERP analysis revealed a parietally located negativity of the negative priming condition compared to the control conditions between 550-730 ms poststimulus. This replicates the findings of Mayr, Niedeggen, Buchner, and Pietrowsky (2003) . The ERP correlate was more pronounced for slow trials (above intraindividual median) than for fast trials (below intraindividual median). The dependency of the negative priming effect size on the reaction time level found in the reaction time analysis as well as in the ERP analysis is consistent with both the inhibition as well as the episodic retrieval account of negative priming. A methodological artifact explanation of this effect-size dependency is discussed and discarded.
An ERP Investigation of Semantic Priming, Repetition Priming, and Negative Priming in Schizophrenic Patients
Authors: Wagner Michael , Baving Lioba , Berg Patrick , Cohen Rudolf , Rockstroh Brigitte
Published: July 2006

The processing of attended and nonattended stimuli in schizophrenic patients was examined with event-related potentials (ERPs) in a lexical decision task. In positive semantic and repetition priming the N400 amplitude did not differ between a group of 17 medicated schizophrenic patients and a group of 20 matched healthy controls. However, negative priming affected the N400 only in controls. Reaction time effects were dissociated from these ERP effects, with patients showing stronger positive priming than controls but identical negative priming. The semantic processes related to the N400 appear to be intact in schizophrenic patients, but patients seem to incorporate less context information (about the nonattended prime) in their episodic memory traces. A stronger increase of the posterior late positive complex in parallel to the stronger positive priming in schizophrenic patients may reflect relatively stronger automatic memory retrieval processes in patients.
β2‐Adrenoceptor agonist‐mediated inhibition of human airway smooth muscle cell proliferation: importance of the duration of β2‐adrenoceptor stimulation
Authors: Stewart Alastair G. , Tomlinson Paul R. , Wilson John W.
Published: July 2006

Airway hyperresponsiveness in asthma has been ascribed to airway wall thickening as a result of smooth muscle proliferation and hypertrophy. We have previously shown that continuous exposure to the β2‐adrenoceptor agonist, salbutamol inhibits mitogen‐induced proliferation of airway smooth muscle cells. In the present study, the effects of variable durations and repeated periods of exposure to β2‐adrenoceptor agonists on DNA synthesis in human cultured airway smooth muscle have been investigated to model some of the possible pharmacokinetic profiles of these agents following inhalation. DNA synthesis was measured by [3H]‐thymidine incorporation.

Shorter periods of exposure (up to 2.5 h) of airway smooth muscle cells to salbutamol (100 nM) commencing 30 min before thrombin (0.3 u ml−1) stimulation had no effect on the subsequent increase in [3H]‐thymidine incorporation. However, inhibition by salbutamol was evident with a 4.5 h exposure and was maximal after an 8.5 h exposure. Similar patterns of results were observed when fenoterol (100 nM) was used in place of salbutamol as the β2‐adrenoceptor agonist or when epidermal growth factor (300 pM) was used in place of thrombin as the mitogen. Salbutamol had no effect on thrombin‐stimulated [3H]‐leucine incorporation after 8.5 h of exposure, but a statistically significant effect was observed after 48 h of exposure.

Experiments in which DNA synthesis was measured up to 52 h after the addition of thrombin indicated that exposure to salbutamol during the first 8 h of mitogen stimulation delayed rather than inhibited the DNA synthesis.

Addition of salbutamol (100 nM) at different times either before or up to 24 h after the addition of thrombin indicated that [3H]‐thymidine incorporation (measured between 24 and 28 h after thrombin) could be significantly attenuated when salbutamol was added as late as 18 h after the addition of thrombin.

The effects of more prolonged exposure to salbutamol were investigated by the addition of salbutamol for either 15 or 24 h per day for a total of 3 days. There were no significant differences in the level of inhibition of thrombin‐stimulated [3H]‐thymidine incorporation between continuous and intermittent salbutamol over the 3 day period and the inhibition was also not different to that achieved with a single continuous exposure to salbutamol over 28 h.

These results indicate that although exposure to β2‐adrenoceptor agonists during the first 8 h of mitogen stimulation does not have a sustained inhibitory effect on DNA synthesis, repeated intermittent or prolonged continuous exposures to salbutamol do inhibit DNA synthesis, without evidence of marked desensitization.
Pharmacological properties of non‐adrenergic, non‐cholinergic inhibitory transmission in chicken gizzard
Authors: Komori S. , Unno T. , Ohashi H.
Published: July 2006

Non‐adrenergic, non‐cholinergic (NANC) inhibitory transmission in chicken gizzard was studied by use of intracellular microelectrode techniques. Changes in membrane potential in response to NANC nerve stimulation were recorded in the gizzard smooth muscle pretreated with atropine (1 μM) and guanethidine (1 μM).

Field stimulation of the intramural nerves (FS) evoked inhibitory junction potentials (i.j.ps) which were abolished by tetrodotoxin (1 μM), but not inhibited at all by K+ channel blockers including apamin (0.5 μM), tetraethylammonium (TEA, 10 mM), charybdotoxin (0.2 μM) and glibenclamide (10 μM).

NG‐nitro‐L‐arginine (300 μM), an inhibitor of nitric oxide (NO) synthase, inhibited i.j.ps. The effect was reversed by L‐arginine (3 mM), but not by D‐arginine (3 mM).

8‐Bromo cyclic GMP (100 μM), a membrane permeable analogue of cyclic GMP, produced a membrane hyperpolarization which was blocked by TEA (10 mM) or glibenclamide (10 μM).

NO at concentrations of up to 400 μM affected neither i.j.ps nor resting membrane potential. On the other hand, NO (80 μM) caused the membrane to hyperpolarize in the smooth muscle of guinea‐pig ileum.

These results suggest that in the chicken gizzard, NANC i.j.ps may not arise from opening of conventional types of K+ channel and that NO seems unlikely to be involved in the generation of i.j.ps. A possible mechanism by which the inhibitory effect of NG‐nitro‐L‐arginine on i.j.ps was brought about will be discussed.
Investigation of the inhibition by acetylshikonin of the respiratory burst in rat neutrophils
Authors: Wang Jih P. , Tsao Lo T. , Raung Shue L. , Hsu Mei F. , Kuo Sheng C.
Published: July 2006

The ability of acetylshikonin to inhibit the respiratory burst in rat neutrophils was characterized and the underlying mechanism of action was also assessed in the present study.

Acetylshikonin caused an irreversible and a concentration‐dependent inhibition of formylmethionyl‐leucyl‐phenylalanine (fMLP) plus dihydrocytochalasin B (CB)‐ and phorbol 12‐myristate 13‐acetate (PMA)‐induced superoxide anion (O2.−) generation with IC50 values of 0.48±0.03 and 0.39±0.03 μM, respectively. Acetylshikonin also inhibited the O2 consumption in neutrophils in response to fMLP/CB as well as to PMA.

Acetylshikonin did not scavenge the generated O2.− in the xanthine‐xanthine oxidase system or during dihydroxyfumaric acid (DHF) autoxidation but, on the contrary, acetylshikonin enhanced the O2.− generation in these cell‐free oxygen radical generating systems.

Acetylshikonin inhibited the formation of inositol trisphosphate (IP3) (39.0±7.8% inhibition at 10 μM, P<0.05) in neutrophils in response to fMLP.

Both the neutrophil cytosolic protein kinase C (PKC) activity and the PMA‐induced PKC associated with the membrane were unaffected by acetylshikonin.

Acetylshikonin did not affect the porcine heart protein kinase A (PKA) activity. Upon exposure to acetylshikonin, the cellular cyclic AMP level was decreased in neutrophils in response to fMLP.

The cellular formation of phosphatidic acid (PA) and, in the presence of ethanol, phosphatidylethanol (PEt) induced by fMLP/CB were inhibited by acetylshikonin (60.1±7.3 and 63.2±10.5% inhibition, respectively, at 10 μM, both P<0.05). Moreover, acetylshikonin attenuated the fMLP/CB‐induced protein tyrosine phosphorylation (about 90% inhibition at 1 μM).

In PMA‐activated neutrophil particulate NADPH oxidase preparations, acetylshikonin did not inhibit, but enhanced, the O2.− generation in the presence of NADPH. However, acetylshikonin decreased the membrane associated p47phox in PMA‐activated neutrophils (about 60% inhibition at 1 μM).

Collectively, these results suggest that the attenuation of protein tyrosine phosphorylation and a failure in the assembly of a functional NADPH oxidase complex probably contribute predominantly to the inhibition of respiratory burst in neutrophils by acetylshikonin. In contrast, the blockade of phospholipase C (PLC) and phospholipase D (PLD) pathways play only a minor role in this respect.
Modulation of excitatory synaptic transmission by nociceptin in superficial dorsal horn neurones of the neonatal rat spinal cord
Authors: Liebel Jörg T. , Swandulla Dieter , Ulrich Zeilhofer Hanns
Published: July 2006

The modulatory actions of nociceptin/orphanin FQ on excitatory synaptic transmission were studied in superficial dorsal horn neurones in transverse slices from 7 to 14 day old rats.

Glutamatergic excitatory postsynaptic currents (e.p.s.cs) were recorded from the somata of the neurones in the whole‐cell patch‐clamp configuration. E.p.s.cs were evoked by extracellular electrical stimulation (100 μs, 3–10 V) of the ipsilateral dorsal root entry zone by use of a glass electrode. E.p.s.cs with constant short latency (<2.3 ms) and with no failures upon stimulation were assumed to be monosynaptic. These e.p.s.cs occurred with an average latency of 1.72±0.098 ms and exhibited a fast decay with a time constant, τ, of 4.8±0.53 ms (n=30).

Nociceptin reversibly reduced the amplitudes of e.p.s.cs in a concentration‐dependent manner in 25 out of 27 cells tested. Average maximum inhibition was 51.6±5.7% (mean±s.e.mean; n=9), at concentrations >3 μM. EC50 was 485±47 nM and the Hill coefficient was 1.29±0.09.

Inhibition of synaptic transmission by nociceptin (10 μM) was insensitive to the non‐specific opioid receptor antagonist naloxone (10 μM) indicating that nociceptin did not act via classical opioid receptors.

In order to determine the site of action of nociceptin spontaneous miniature e.p.s.cs (m‐e.p.s.cs) were recorded. Nociceptin reduced the frequency of m‐e.p.s.cs in 6 out of 7 cells but had no effect on their amplitude distribution or on their time course. These findings suggest a pre‐ rather than a postsynaptic modulatory site of action. This is in line with the finding that current responses elicited by extracellular application of L‐glutamate (10 μM) were not affected by nociceptin (10 μM; n=7).

No positive correlation was found between the degree of inhibition by nociceptin (10 μM) and by the mixed δ‐ and μ‐receptor agonist methionine‐enkephalin (10 μM). This suggests that both neuropeptides acted on different but perhaps overlapping populations of synaptic connections.

Our results indicate that nociceptin inhibits excitatory synaptic transmission in the superficial layers of the rat dorsal horn by acting on presynaptic, presumably ORL1 receptors. This may be an important mechanism for spinal sensory information processing including nociception.
Ro 32‐3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo
Authors: Lewis E. J. , Bishop J. , Bottomley K. M. K. , Bradshaw D. , Brewster M. , Broadhurst M. J. , Brown P. A. , Budd J. M. , Elliott L. , Greenham A. K. , Johnson W. H. , Nixon J. S. , Rose F. , Sutton B. , Wilson K.
Published: July 2006

Ro 32‐3555 (3(R)‐(cyclopentylmethyl) ‐ 2(R) ‐ [(3,4,4 ‐ trimethyl‐2,5‐dioxo‐1‐imidazolidinyl)methyl] ‐ 4‐oxo‐4‐piperidinobutyrohydroxamic acid) is a potent, competitive inhibitor of human collagenases 1, 2 and 3 (Ki values of 3.0, 4.4 and 3.4 nM, respectively). The compound is a selective inhibitor of collagenases over the related human matrix metalloproteinases stromelysin 1, and gelatinases A and B (Ki values of 527, 154 and 59 nM, respectively).

Ro 32‐3555 inhibited interleukin‐1α (IL‐1α)‐induced cartilage collagen degradation in vitro in bovine nasal cartilage explants (IC50=60 nM).

Ro 32‐3555 was well absorbed in rats when administered orally. Systemic exposure was dose related, with an oral bioavailability of 26% at a dose of 25 mg kg−1.

Ro 32‐3555 prevented granuloma‐induced degradation of bovine nasal cartilage cylinders implanted subcutaneously into rats (ED50=10 mg kg−1, twice daily, p.o.).

Ro 32‐3555 dosed once daily for 14 days at 50 mg kg−1, p.o., inhibited degradation of articular cartilage in a rat monoarthritis model induced by an intra‐articular injection of Propionibacterium acnes.

Ro 32‐3555 is a potential therapy for the treatment of the chronic destruction of articulating cartilage in both rheumatoid and osteoarthritis.
Examination of the role of endopeptidase 3.4.24.15 in Aβ secretion by human transfected cells
Authors: Chevallier Nathalie , Jiracek Jirì , Vincent Bruno , Baur Claus‐Peter , Spillantini Maria‐Gracia , Goedert Michel , Dive Vincent , Checler Frédéric
Published: July 2006

We have taken advantage of our recent development of highly potent and specific phosphinic inhibitors of endopeptidase 3.4.24.15 to examine the putative contribution of the enzyme in the secretion of Aβ by HK293 transfected cells overexpressing the wild type and the Swedish (Sw) double mutated form of βAPP751.

First, we showed that HK293 cells contain a peptidase activity, the inhibition profile of which fully matches that of purified endopeptidase 3.4.24.15. Second, we established that the treatment of HK293 cells with specific phosphinic inhibitors leads to about 80% inhibition of intracellular endopeptidase 3.4.24.15 activity, indicating that these inhibitors penetrate the cells.

Metabolic labelling of wild type and SwβAPP751‐expressing cells, followed by immunoprecipitation of Aβ‐containing peptides, revealed the secretion of Aβ and the intracellular formation of an Aβ‐containing 12 kDa product.

Aβ secretion by SwβAPP751 transfected cells was drastically enhanced when compared to cells expressing wild type βAPP751. This production was not affected by endopeptidase 3.4.24.15 inhibitors in either cell type. This correlates well with the observation that endopeptidase 3.4.24.15 does not cleave recombinant baculoviral SwβAPP751, in vitro.

Our previous data indicated that endopeptidase 3.4.24.15 activity was reduced in the parietal cortex of Alzheimer's disease affected brains and that the enzyme probably participated, in this brain area, to the catabolism of somatostatin 1‐14. However, the present work indicates that endopeptidase 3.4.24.15 does not seem to behave as a β‐secretase in HK293 transfected cells. Therefore, it is suggested that endopeptidase 3.4.24.15 could participate in the symptomatology, but probably not in the aetiology of Alzheimer's disease.
Cyclosporine A‐induced increase in glomerular cyclic GMP in rats and the involvement of the endothelinB receptor
Authors: Tack Ivan , Marin‐Castano Encarna , Bascands Jean‐Loup , Pecher Christiane , Ader Jean‐Louis , Girolami Jean‐Pierre
Published: July 2006

A transient two fold increase in the cyclic GMP content was observed in rat freshly isolated glomeruli 6 to 9 h after a single subcutaneous injection of 20 mg kg−1 cyclosporine A (CsA) in conscious animals.

In vitro stimulation with endothelin 3 (ET‐3) of isolated glomeruli obtained from CsA‐untreated rats resulted in a dose‐dependent increase in cyclic GMP content. The increase observed with 10 nM ET‐3 was similar to that observed in glomeruli isolated 9 h after in vivo CsA administration.

The rise in glomerular cyclic GMP content after in vivo CsA injection was prevented by in vivo treatment with L‐NAME (10 mg kg−1) or by in vitro calcium deprivation of the incubation medium.

The stimulating effects of CsA on glomerular cyclic GMP content were inhibited by in vivo administration of the ETB receptor antagonist BQ‐788 (2 mg kg−1) but not by the ETA receptor antagonist BQ‐123 (2 mg kg−1).

The maximum increase in glomerular cyclic GMP content induced in vitro by acetylcholine (100 μM) and by ET‐3 (100 nM) was slightly lower (approximately by 20–25%, P<0.05) in glomeruli from CsA‐treated rats than in glomeruli from untreated rats. In contrast, the maximum increase achieved with 1 μM sodium nitroprusside was similar in both groups.

A single subcutaneous injection of CsA did not significantly alter the glomerular mRNA expression of constitutive endothelial NO synthase (eNOS), as evaluated by RT–PCR, whereas the mRNA expression of the inducible NO synthase (iNOS), which follows pretreatment with lipopolysaccharide, was prevented.

These results indicate that in vivo administration of a single dose of cyclosporine A transiently increases the cyclic GMP content of freshly isolated glomeruli, and that activation of ETB receptors and stimulation of the NO pathway are involved in this process. Furthermore, a single administration of CsA does not impair eNOS mRNA expression and only slightly reduces NO‐dependent glomerular cyclic GMP production.
Specific Gq protein involvement in muscarinic M3 receptor‐induced phosphatidylinositol hydrolysis and Ca2+ release in mouse duodenal myocytes
Authors: Morel J. L. , Macrez N. , Mironneau J.
Published: July 2006

Cytosolic Ca2+ concentration ([Ca2+]i) during exposure to acetylcholine or caffeine was measured in mouse duodenal myocytes loaded with fura‐2. Acetylcholine evoked a transient increase in [Ca2+]i followed by a sustained rise which was rapidly terminated after drug removal. Although L‐type Ca2+ currents participated in the global Ca2+ response induced by acetylcholine, the initial peak in [Ca2+]i was mainly due to release of Ca2+ from intracellular stores.

Atropine, 4‐diphenylacetoxy‐N‐methylpiperidine (4‐DAMP, a muscarinic M3 antagonist), pirenzepine (a muscarinic M1 antagonist), methoctramine and gallamine (muscarinic M2 antagonists) inhibited the acetylcholine‐induced Ca2+ release, with a high affinity for 4‐DAMP and atropine and a low affinity for the other antagonists. Selective protection of muscarinic M2 receptors with methoctramine during 4‐DAMP mustard alkylation of muscarinic M3 receptors provided no evidence for muscarinic M2 receptor‐activated [Ca2+]i increase.

Acetylcholine‐induced Ca2+ release was blocked by intracellular dialysis with a patch pipette containing either heparin or an anti‐phosphatidylinositol antibody and by external application of U73122 (a phospholipase C inhibitor).

Acetylcholine‐induced Ca2+ release was insensitive to external pretreatment with pertussis toxin, but concentration‐dependently inhibited by intracellular dialysis with a patch pipette solution containing an anti‐αq/α11 antibody. An antisense oligonucleotide approach revealed that only the Gq protein was involved in acetylcholine‐induced Ca2+ release.

Intracellular applications of either an anti‐βcom antibody or a peptide corresponding to the Gβγ binding domain of the β‐adrenoceptor kinase 1 had no effect on acetylcholine‐induced Ca2+ release.

Our results show that, in mouse duodenal myocytes, acetylcholine‐induced release of Ca2+ from intracellular stores is mediated through activation of muscarinic M3 receptors which couple with a Gq protein to activate a phosphatidylinositol‐specific phospholipase C.
Comparison of the nitric oxide and cyclo‐oxygenase pathway in mesenteric resistance vessels of normotensive and spontaneously hypertensive rats
Authors: Le Marquer‐Domagala F. , Finet M.
Published: July 2006

The double perfused mesentery was used to compare arterial and venous KCl‐ and acetylcholine (ACh)‐induced responses in tissues taken from normotensive (WKY) and spontaneously hypertensive rats (SHR), in the presence or absence of inhibitors of nitric oxide (NO) synthase (NG‐nitro‐L‐arginine (L‐NOARG) and NG‐nitro‐L‐arginine methyl ester (L‐NAME)) and cyclo‐oxygenase (indomethacin, mefenamic acid).

KCl (20 to 120 mM K+) caused concentration‐dependent increases in arterial and venous perfusion pressures. The maximal arterial effects were significantly higher in the SHRs than in the WKY, with no differences in the venous pressor responses.

L‐NAME and L‐NOARG (100 μM) had no effect on the basal perfusion pressures in tissues from either WKY or SHRs, and mefenamic acid only induced a significant reduction of the basal perfusion pressures in the venous mesenteric vessels isolated from WKY.

L‐NAME and L‐NOARG (100 μM) potentiated the pressor responses to KCl to the same extent in the venous and arterial beds derived from WKY and SHR, while indomethacin and mefenamic acid (5 μM) only significantly decreased these responses in WKY.

Acetylcholine (ACh)‐induced relaxations (1 nM to 10 μM) were significantly higher in arterial beds of WKY than in SHR, without differences in the venous relaxant responses.

L‐NAME (100 μM) inhibited ACh‐induced relaxations in arterial and venous beds from both groups of rats. Mefenamic acid was without effect on ACh‐induced relaxations in either the arterial or the venous beds from WKY and SHR.

In conclusion, the liberation of NO in the perfused mesenteric vasculatures requires an active tone and no dysfunction of NO synthase activity is functionally apparent in the mesenteries isolated from SHRs. The cyclo‐oxygenase pathway is only implicated in the KCl‐induced responses of tissues derived from WKY, but not in the vasodilatations induced by ACh in either the arterial or the venous vasculatures from WKY and SHR.
Attenuation of precipitated morphine withdrawal symptoms by acute i.c.v. administration of a group II mGluR agonist
Authors: Fundytus Marian E. , Coderre Terence J.
Published: July 2006

We previously showed that chronic i.c.v. antagonism of metabotropic glutamate receptors (mGluRs) concurrently with s.c. morphine significantly attenuated precipitated withdrawal symptoms. Conversely, acute i.c.v. injection of a selective group II mGluR antagonist just before the precipitation of withdrawal exacerbated abstinence symptoms.

In the present study, we showed that acute i.c.v. administration of the non‐selective mGluR agonist 1‐aminocyclopentane‐1,3‐dicarboxylic acid ((1S,3R)‐ACPD), as well as the group II selective agonist (2S,1′R,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine (DCG‐IV), significantly attenuated the severity of precipitated withdrawal symptoms.

From these results we hypothesize that chronic opioid treatment may indirectly induce a desensitization of group II mGluRs, which contributes to the development of dependence.
Time evolution of the electron diffusion region and the reconnection rate in fully kinetic and large system
Authors: Fujimoto Keizo
Published: July 2006

Time evolutions of the electron diffusion region embedded in the ion-scale diffusion region and the reconnection rate associated with magnetic reconnection are investigated using 2-1/2 dimensional full kinetic simulations in a large system, so that any effects of the downstream boundary conditions are negligible. The simulation code employs the adaptive mesh refinement technique and the particle splitting algorithm to the conventional particle-in-cell code, which enable us to perform large-scale full particle simulations. It is shown that the reconnection rate increases associated with magnetic reconnection and reaches a peak value large enough for fast reconnection, but then it decreases as time goes on, even though the effects of the system boundary are negligible. The key process responsible for slowing the reconnection processes is the extension of the electron diffusion region in association with the enhancement of the polarization electric field directing toward the neutral sheet in the electron inflow region. The polarization electric field is caused by the inertia difference between ions and electrons, and enhanced by the meandering motions of the background ions. In order to confirm the role of the polarization electric field, we compare the simulation results with mi∕me=1 and 100. It is found that (1) a quasi-steady reconnection is achieved in the system where the polarization electric field does not arise, (2) a large reconnection rate is obtained, even in the system without the Hall effects. It is suggested that the anomalous resistivity due to the Buneman-type instability might be required to support a steady-state fast reconnection.