bluuebunny/crossref_metadata_2025 huggingface dataset:
Impairment of stress adaptive behaviours in rats by the CCKA receptor antagonist, devazepide
Authors: Hernando Fernando , Fuentes José A. , Ruiz‐Gayo Mariano
Published: July 2012

Cholecystokinin (CCK) is released during stress both in limbic and hypothalamic areas suggesting that CCK could participate in modulating neuroendocrine as well as behavioural responses to stress.

In this study we have examined the effect of CCK receptor antagonists on the retention of the immobility response to a forced‐swim stress in rats. In this test, rats are forced to swim during 15 min (conditioning period) and 24 h later, the duration of immobility is measured during a period of 5 min (re‐test period). During the conditioning period rats display a period of vigorous activity, followed by progressive inactivity. During the re‐test period rats remain 70–80% of the time in an immobile posture.

The CCKA receptor antagonist, devazepide (MK‐329) but not the CCKB receptor antagonist, L‐365,260, administered s.c. immediately before the conditioning period, decreased the duration of acquired immobility during the re‐test period. The effect of devazepide was prevented by cholecystokinin octapeptide (CCK‐8; 40 μg kg−1, s.c.) as well as by the selective glucocorticosteroid GII receptor agonist, dexamethasone (30 μg kg−1, s.c.).

Neither corticosterone nor ACTH plasma levels measured both after the re‐test period and after the conditioning period were modified by devazepide treatment.

The results suggest a role for CCK in the behavioural adaptation to stress and indicate a relationship between CCK systems and glucocorticoids in the neuronal mechanisms involved in the acquisition of adaptive behaviours to stress.
Stimulation of sodium pump by vasoactive intestinal peptide in guinea‐pig isolated trachea: potential contribution to mechanisms underlying relaxation of smooth muscle
Authors: Morrison Keith J. , Vanhoutte Paul M.
Published: July 2012

Relaxation of airway smooth muscle induced by vasoactive intestinal peptide (VIP) is mediated by adenosine 3′:5′ cyclic monophosphate (cyclic AMP). An interaction between the synthesis of cyclic AMP and enzymic activity of the plasmalemmal sodium pump (Na+‐K+‐ATPase) exists in certain isolated cell systems. This study sought to determine the contribution of Na+‐K+‐ATPase activity to relaxation of airway smooth muscle evoked by VIP.

All experiments were performed on isolated strips of guinea‐pig trachea from which the epithelium had been removed. VIP was a more potent relaxant in tissues that were contracted with carbachol than those contracted with an equi‐effective depolarizing concentration of K+.

Ouabain (0.1 μm‐10 μm) induced contraction of tracheal strips. Contraction to ouabain (5 μm) was abolished following incubation of tissues with K+‐free, or Ca2+‐free (+EGTA, 0.1 mM) physiological solutions. The contractile response to ouabain (5 μm) was not influenced significantly by exposure of the tissues to atropine (1 μm), phentolamine (5 μm) and diphenhydramine (1 μm) for 60 min.

Tissues were incubated with ouabain (5 μm; 60 min) or K+‐free physiological solution (60 min) to inhibit Na+‐K+‐ATPase activity. These procedures reduced relaxation induced by VIP, peptide histidine isoleucine, forskolin, isoprenaline and sodium nitroprusside.

Relaxation to VIP was impaired significantly following exposure of tissues to a low Na+ solution (30 min) or amiloride (500 μm; 30 min).

Ouabain‐sensitive uptake of 86Rb was measured in tracheal strips (devoid of epithelium and cartilage) as an index of Na+‐K+‐ATPase activity. VIP (1 μm; 2 min) caused a 4.7 fold stimulation of ouabain‐sensitive uptake of 86Rb. This effect was impaired significantly by low Na+ solution.

The results suggest that (i) relaxation of tracheal smooth muscle to VIP is sensitive to procedures that inhibit activity of Na+‐K+‐ATPase and invoke a role for altered sodium pump function in the mechanisms that underlie cyclic AMP‐dependent relaxation; and (ii) VIP stimulates ouabain‐sensitive uptake of 86Rb in airway smooth muscle in a Na+‐dependent manner.
Measurement of lipocortin 1 levels in murine peripheral blood leukocytes by flow cytometry: modulation by glucocorticoids and inflammation
Authors: Perretti Mauro , Flower Roderick J.
Published: July 2012

Lipocortin 1 (LC1) immunoreactivity in murine peripheral blood leukocytes was quantified by use of a flow cytometric technique associated with a permeabilisation protocol with saponin. Using specific antisera raised against the whole protein or against its N‐terminus peptide, cell‐associated LC1‐like immunoreactivity was easily detected in circulating neutrophils and monocytes, whereas very low levels were found in lymphocytes. Of the total protein measured 17.6% and 36% were associated with the external plasma membrane in neutrophils and monocytes, as assessed in the absence of cell permeabilisation, whereas no signal was detected on lymphocyte plasma membrane.

Treatment of mice with dexamethasone (Dex; 0.5‐5 μg per mouse corresponding to ∼ 0.015‐1.5 mg kg−1) increased LC1 levels in neutrophils and monocytes. The 2–3 fold increase in LC1 levels was time‐dependent with a peak at 2 h. Treatment of mice with the steroid antagonist, RU486 (two doses of 20 mg kg−1 orally) decreased LC1‐like immunoreactivity in all three types of circulating leukocytes by ≥50%.

Extravasation of blood neutrophils into inflamed tissue sites resulted in a consistent reduction (≥50%) in LC1 levels compared with circulating neutrophils. A high LC1‐like immunoreactivity was also measured in resident macrophages, of which approximately one third was membrane‐associated. Induction of an acute inflammatory response in the murine peritoneal cavity did not modify total LC1 levels measured in macrophages, but reduced membrane‐associated LC1 to a significant extent, i.e. up to 70%.

In conclusion, flow cytometric analysis is a rapid and convenient method for detecting and measuring LC1 in murine leukocytes. We confirmed that LC1 protein expression is controlled by exogenous and endogenous glucocorticoids. Amongst other factor(s) influencing protein concentrations, extravasation was found to be associated with a reduced LC1 expression in the emigrated cells.
Reciprocal inhibition of nitric oxide and prostacyclin synthesis in human saphenous vein
Authors: Barker J.E. , Bakhle Y.S. , Anderson J. , Treasure T. , Piper P.J.
Published: July 2012

Angiotensin II (AII) causes contraction of isolated rings of human saphenous vein, responses that are attenuated by the presence of functional endothelium. In this study, we have investigated the mechanisms controlling the release by AII of two endothelial‐derived vasorelaxants, prostacyclin (PGI2) and nitric oxide (NO).

Myotropic and biochemical changes were measured in response to AII. The biochemical responses measured were the output of PGI2 (as 6‐oxo‐PGF1α) and of NO (as cyclic GMP). Inhibitors of cyclo‐oxygenase (COX; piroxicam) or NO synthase (NOS; L‐NAME), were added to the system to determine the influence of endogenous prostaglandins and NO on both myotropic and biochemical responses. Furthermore, to mimic the effects of endogenous, PGI2 or NO, exogenous forms of these relaxants were added, during inhibition of their endogenous release.

Contractions of the rings of saphenous vein in response to AII (1–100 nM) were unaffected by treatment with either piroxicam (5 μm) or L‐NAME (200 μm) individually. However, when these two inhibitors were used together, there was an increase in the contractions in response to AII.

Biochemical analyses revealed that during stimulation by AII, levels of PGI2 and NO were enhanced when synthesis of the other vasodilator was inhibited, suggesting that endogenous NO inhibits PGI2 synthesis and endogenous, PGI2 or another vasorelaxant PG can inhibit NO synthesis.

Exogenous PGI2 (as iloprost) or NO (from glyceryl trinitrate) inhibited the increased output of endogenous NO or PGI2 respectively.

These results demonstrate the presence, in human saphenous vein, of a mechanism which ensures that levels of vasodilatation are maintained through a compensatory increase in one relaxant agonist when output of the other is decreased. If present in vivo such a mechanism would be important in maintaining saphenous vein graft patency as both PGI2 and NO are not only vasodilators, but inhibit platelet aggregation and myoinitimal hyperplasia, processes implicated in degeneration of graft function.
Effect of calmodulin antagonists on calmodulin‐induced biphasic modulation of Ca2+‐induced Ca2+ release
Authors: Ikemoto Takaaki , Lino Masamitsu , Endo Makoto
Published: July 2012

Calmodulin (CaM) has a biphasic effect on Ca2+‐induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR): potentiation and inhibition at low (pCa > 6.0) and high (pCa 5) Ca2+ concentrations, respectively. To characterize the mode of action of CaM, we studied the effect of CaM antagonists on the CICR in skinned muscle fibres of the rabbit. Ca2+ release was measured by microfluorometry with Fura‐2.

A CaM antagonist, trifluoperazine (TFP), potentiated the CICR in a dose‐dependent manner (10–300 μm) at pCa 6, where a simple reversal of the CaM effect would be inhibition of the CICR. Furthermore, 100 μm TFP sensitized the CICR to Ca2+. A similar effect was produced by other CaM antagonists that were tested: chlorpromazine, W‐7, mastoparan, and peptide fragment of CaM‐binding residues of CaM‐dependent protein kinase II.

The biphasic effect of CaM on the CICR was observed even in the presence of high concentrations of CaM antagonists or CaM‐binding peptides.

From these results we suggest that CaM has a unique mode of action on the CICR which is quite different from the effect of CaM on known enzymes.
Antithrombotic actions of the thrombin inhibitor, argatroban, in a canine model of coronary cyclic flow: comparison with heparin
Authors: Duval N. , Lunven C. , O'Brien D.P. , Grosset A. , O'Connor S.E. , Berry C.N.
Published: July 2012

The antithrombotic action of argatroban, a synthetic thrombin inhibitor, was studied in a canine model of coronary cyclic flow having some of the characteristics of acute unstable angina. Heparin was studied as a reference anticoagulant.

Localized endothelial damage was induced in the circumflex coronary artery of anaesthetized open‐chest foxhounds and a critical stenosis was applied by use of a Lexan constrictor placed around the artery at the site of endothelial damage. An electro‐magnetic flow probe was placed distal to the lesion, and cyclic flow variations (CFVs) were observed, as thrombi formed at the site of the arterial lesion and were dislodged. Test compounds were administered by i.v. infusion commencing 1 h after the appearance of CFVs, and maintained for 1 h. On termination of the treatments, coronary flow was observed for a further 60 min. A series of blood samples were taken at predetermined times throughout each experiment in order to determine the coagulation parameters, thrombin time (TT) activated partial thromboplastin time (aPTT) and for the determination of fibrinopeptide A (FpA) levels before, during and post‐treatment.

Argatroban and heparin showed antithrombotic effects in this model. Argatroban dose‐dependently increased the minimum coronary flow at the nadir of the CFVs from 5.4 ± 1.7 to 9.1 ± 2.1 ml min−1 (30 μg kg−1 min−1, P = 0.041) and from 2.9 ± 0.9 to 16.3 ± 4.5 ml min−1 (100 μg kg−1 min−1, P = 0.023, n = 8 dogs at each dose level). Heparin (5 and 15 iu kg−1 min−1) also increased minimum flow, but the increase was not statistically significant at the 5% level, although the P value in animals treated with 15 iu kg−1 min−1 (P = 0.0521, n = 6 dogs) fell just outside this limit. Although neither compound significantly decreased the overall CFV frequency, argatroban (100 μg kg−1 min−1) significantly (P < 0.01) decreased the number of large amplitude CFVs (minimum coronary flow < 10 ml min−1) by 63%, and heparin (15 iu kg−1 min−1) caused a 50% decrease in this parameter (P < 0.05).

The thrombin times were increased by a factor greater than 10 during antithrombotic treatment, irrespective of the compound or doses used. Heparin treatment induced 17 and > 30 fold increases in aPTT at 5 and 15 iu kg−1 min−1 respectively. However, argatroban produced only 2 and 3 fold increases in aPTT at 30 and 100 μg kg−1 min−1, despite significant antithrombotic effects. FpA levels were reduced in the presence of both argatroban and heparin.

These data show that, when administered as an intravenous infusion, argatroban is a potent antithrombotic agent in a canine model of coronary cyclic flow.
Characterization of the anatomical structures involved in the contractile response of the rat lung periphery
Authors: Salerno Francesco G. , Kurosawa Hajime , Eidelman David H. , Ludwig Mara S.
Published: July 2012

When lung parenchymal strips are challenged with different smooth muscle agonists, the tensile and viscoelastic properties change. It is not clear, however, which of the different anatomical elements present in the parenchymal strip, i.e., small vessel, small airway or alveolar wall, contribute to the response.

Parenchymal lung strips from Sprague Dawley rats were suspended in an organ bath filled with Krebs solution (37°C, pH = 7.4) bubbled with 95%O2/5%CO2. Resting tension (T) was set at 1.1 g and sinusoidal oscillations of 2.5% resting length (Lo) at a frequency of 1 Hz were applied. Following 1 h of stress adaptation, measurements of length (L) and T were recorded under baseline conditions and after challenge with a variety of pharmacological agents, i.e., acetylcholine (ACh), noradrenaline (NA) and angiotensin II (AII). Elastance (E) and resistance (R) were calculated by fitting changes in T, L and ΔL/Δt to the equation of motion. Hysteresivity (η, the ratio of the energy dissipated to that conserved) was obtained from the equation η = (R/E)2πf.

In order to determine whether small airways or small vessels accounted for the responses to the different pharmacologic agents, further studies were carried out in lung explants. Excised lungs from Sprague Dawley rats were inflated with agarose. Transverse slices of lung (0.5–1.0 mm thick) were cultured overnight. By use of an inverted microscope and video camera, airway and vascular lumen area were measured with an image analysis system.

NA, ACh and AII constricted the parenchymal strips. Airways constricted after all agonists, vessels constricted only after AII. Atropine (Atr) pre‐incubation decreased the explanted airway and vessel response to AII, but no difference was found in the parenchymal strip response.

Preincubation with the arginine analogue Nω‐nitro‐L‐arginine (L‐NOARG) did not modify the response to ACh but mildly increased the oscillatory response to NA after co‐preincubation with propranolol (Prop).

These results suggest that during ACh and NA challenge, small vessels do not contribute substantially to the parenchymal strip response. The discrepancy between results in airways, vessels and strips when Atr was administered prior to AII implicates a direct contractile response in the parenchymal strip.
Inhibition by endothelin‐1 of cholinergic nerve‐mediated acetylcholine release and contraction in sheep isolated trachea
Authors: Henry Peter J. , Shen Albert , Mitchelson Fred , Goldie Roy G.
Published: July 2012

The relative roles of ETA and ETB receptor activation on cholinergic nerve‐mediated contraction and acetylcholine (ACh) release were examined in sheep isolated tracheal smooth muscle.

Electrical field stimulation (EFS; 90 V, 0.5 ms duration, 1 Hz, 10 s train) applied to sheep isolated tracheal smooth muscle strips induced monophasic contractile responses that were abolished by either 1 μm tetrodotoxin or 0.1 μm atropine, but were insensitive to 10 μm hexamethonium and 100 μm L‐NAME. Thus, EFS‐induced contractions resulted from the spasmogenic actions of ACh released from parasympathetic, postganglionic nerves.

As expected, sheep isolated tracheal smooth muscle preparations did not contract in response to the ETB receptor‐selective agonist, sarafotoxin S6c (0.1–100 nM). However, sarafotoxin S6c caused a concentration‐dependent and transient inhibition of EFS‐induced contractions. The inhibitory effect induced by a maximally effective concentration of sarafotoxin S6c (10 nM; 72.1 ± 5.7%, n = 6) was abolished in the presence of the ETB receptor‐selective antagonist BQ‐788 (1 μm). Contractile responses to exogenously administered ACh (10 nM‐0.3 mM) were not inhibited by sarafotoxin S6c (1 or 10 nM; n = 7).

In contrast to sarafotoxin S6c, endothelin‐1 induced marked contractions in sheep isolated tracheal smooth muscle. These contractions were inhibited by BQ‐123, consistent with an ETA receptor‐mediated response. In the presence of BQ‐123 (3 μm), endothelin‐1 produced a concentration‐dependent inhibition of EFS‐induced contractions (30 nM endothelin‐1, 68.9 ± 10.2% inhibition, n = 5). These responses were inhibited by 1 μm BQ‐788, indicative of an ETB receptor‐mediated process. Endothelin‐1 was about 3 fold less potent than sarafotoxin S6c.

EFS (90 V, 0.5 ms duration, 1 Hz, 15 min train) induced the release of endogenous ACh (1.94 ± 0.28 pmol mg−1 tissue, n = 12), as assayed by h.p.l.c. with electrochemical detection. EFS‐induced release of ACh was inhibited to a similar extent by 100 nM endothelin‐1 (47 ± 4%, n = 9) and 10 nM sarafotoxin S6c (46 ± 9%, n = 3). These effects of endothelin‐1 on ACh release were inhibited by 1 μm BQ‐788 alone (n = 4), by BQ‐788 in the presence of 3 μm BQ‐123 (n = 4), but not by 3 μm BQ‐123 alone (n = 5).

In summary, sheep isolated tracheal smooth muscle contains two anatomically and functionally distinct endothelin receptor populations. ETA receptors located on airway smooth muscle mediate contraction, whereas ETB receptors appear to exist on cholinergic nerves that innervate tracheal smooth muscle cells and mediate inhibition of ACh release. The inhibitory effect of ETB receptor stimulation on cholinergic neurotransmission is in stark contrast to the enhancing effects hitherto described in the airways.
Adenosine inhibitory effect on enhanced growth of aortic smooth muscle cells from streptozotocin‐induced diabetic rats
Authors: Parés‐Herbuté N. , Hillaire‐Buys D. , Etienne P. , Gross R. , Loubatières‐Mariani M.‐M. , Monnier L.
Published: July 2012

There is evidence to suggest that adenosine may regulate arterial smooth muscle cell (SMC) growth and proliferation, which is a key event in atherogenesis. This regulation may be mediated via adenylate cyclase. As diabetes is a known risk factor for atherosclerosis, we investigated the growth of aortic SMC from diabetic rats in primary culture and their sensitivity to adenosine and to adenylate cyclase activity.

Diabetes was induced with streptozotocin (STZ, 66 mg kg−1, i.p.) Aortic SMC primary cultures were prepared from STZ‐diabetic and age‐matched rats 5 weeks after the STZ injection.

SMC from STZ‐diabetic rats grew faster and reached greater densities at confluence than those from non‐diabetic animals.

Adenosine inhibited growth in both control and diabetic SMC. However, cells from STZ‐diabetic rats were apparently more sensitive to adenosine.

Direct activation of adenylate cyclase by forskolin induced a dose‐dependent growth inhibition, similar in both groups of cells.

Cholera toxin, an activator of stimulatory GTP‐binding protein (Gs), induced a similar growth inhibitory response in non‐diabetic and diabetic SMC. Pertussis toxin (PTX), an inactivator of inhibitory GTP‐binding protein (Gi), did not itself affect SMC growth. However, PTX increased dose‐dependently the growth inhibition induced by adenosine in SMC from non‐diabetic rats but not in SMC from diabetic rats.

These findings suggest a functional abnormality in Gi activity in SMC from diabetic rats, that would explain the increased sensitivity to the nucleoside. This impaired inhibitory pathway may reflect changes in the growth regulation of SMC in experimental diabetic states.
Mechanism of inhibition of calcium channels in rat nucleus tractus solitarius by neurotransmitters
Authors: Rhim Hyewhon , Toth Peter T. , Miller Richard J.
Published: July 2012

High‐threshold Ca2+ channel currents were measured every 15 s following a 200 ms voltage step from −80 mV to 0 mV in order to study the coupling mechanism between neurotransmitter receptors and Ca2+ channels in neurones acutely isolated from the nucleus tractus solitarius (NTS) of the rat.

Application of 30 μm baclofen (GABAB receptor agonist) caused 38.9 ± 1.2% inhibition of the peak inward Ba2+ current (IBa2+) in most NTS cells tested (n = 85 of 88). Somatostatin, 300 nM, also reduced IBa2+ by 31.3 ± 1.6% in 53 cells of 82 tested.

Activation of μ‐opioid‐, GABAB‐ or somatostatin‐receptors inhibited both N‐ and P/Q‐type Ca2+ channels.

The inhibition of Ca2+ currents by DAMGO (μ‐opioid receptor agonist), baclofen and somatostatin was reduced by treatment with pertussis toxin and partially relieved by application of a 50 ms conditioning prepulse to +80 mV. This suggests that a pertussis toxin‐sensitive G‐protein was involved in the neurotransmitter‐mediated action in the observed inhibition of Ca2+ currents.

Intracellular loading with an antiserum raised against the amino terminus of Goα (GC/2) markedly attenuated the somatostatin‐induced inhibition, but did not block the DAMGO‐ and baclofen‐induced inhibition.

These findings suggest at least two different pertussis toxin‐sensitive G‐protein‐mediated pathways are involved in receptor‐induced inhibition of Ca2+ currents in the NTS.
The induction of a biphasic bronchospasm by the ETB agonist, IRL 1620, due to thromboxane A2 generation and endothelin‐1 release in guinea‐pigs
Authors: Noguchi Seiji , Kashihara Yasunari , Bertrand Claude
Published: July 2012

IRL 1620 (0.01‐0.1 mg kg−1, i.v.), a selective endothelin B (ETB) receptor agonist, induced a dose‐dependent biphasic increase in total lung resistance and a decrease in dynamic compliance in anaesthetized and artificially ventilated guinea‐pigs. After intravenous injection of IRL 1620 (0.03 mg kg−1), the first phase was observed within 2 min whereas the second phase started between 5 and 10 min after injection and was long lasting.

In order to characterize which endothelin receptors are involved in both phases of bronchoconstriction, we studied the effect of ETA and ETB receptor antagonists (BQ 123 and BQ 788, respectively). BQ 788 (0.1‐1 mg kg−1, i.v.) inhibited, in a dose‐dependent manner, both phases of bronchoconstriction. BQ 123 (3 mg kg−1, i.v.) markedly inhibited (by 76%) the second phase of bronchoconstriction but had no effect on the early component of the response.

The effect of atropine, neurokinin‐1 (NK1) and neurokinin‐2 (NK2) receptor antagonists (SR140333 and SR48968, respectively) were tested to investigate the possible involvement of cholinergic and sensory nerve activation, respectively, in the response to IRL 1620. Likewise, the role of arachidonic acid metabolites (leukotriene D4 antagonist, ONO‐1078 and thromboxane A2 (TXA2) inhibitor, OKY‐046) in this response was also investigated. OKY‐046 (1 mg kg−1, i.v.) and atropine (1 mg kg−1, i.v.) partially inhibited the first phase (by 80% and 20%, respectively) without affecting the late phase of bronchoconstriction. Neither ONO‐1078 (1 mg kg−1, i.v.) nor the combination of SR140333 (0.2 mg kg−1, i.v.) and SR 48968 (0.2 mg kg−1, i.v.) modified IRL 1620‐induced bronchoconstriction.

A low dose of IRL 1620 (0.005 mg kg−1, i.v.) induced a monophasic bronchoconstriction. Pretreatment by phosphoramidon (100 μmol kg−1, i.v.) restored the second phase of bronchoconstriction. In this condition, BQ 123 (3 mg kg−1, i.v.) was able to inhibit partially the second phase of bronchoconstriction.

These results suggest that both phases of bronchoconstriction induced by IRL 1620 were mediated primarily by ETB receptor activation, the first phase being a consequence of TXA2 and acetylcholine release. The inhibition by an ETA receptor antagonist and the restoration by a neutral endopeptidase (NEP) inhibitor of the second phase of bronchoconstriction suggests that primary activation of ETB receptors leads to autocrine/paracrine endothelin‐1 (ET‐1) release that would subsequently cause profound bronchoconstriction through both ETA and ETB receptor activation.
Central B2 receptor involvement in the antinociceptive effect of bradykinin in rats
Authors: Pelá I.R. , Rosa A.L. , Silva C.A.A. , Huidobro‐Toro J.P.
Published: July 2012

The effect of intracerebroventricular (i.c.v.) injection of bradykinin (BK) and related peptides was tested on the dental pulp electrical stimulation threshold (DPEST) in rats.

BK (4, 8 and 16 nmol) induced a dose‐dependent increase of DPEST, indicative of an antinociceptive effect.

I.c.v. injection of equimolar doses of BK‐related peptides, Lys‐BK and Met‐Lys‐BK, also induced an increase of DPEST, but the magnitude of the effect was not as intensive as that induced by BK, when the maximum increase of DPEST was considered. The peptide T‐kinin induced a short lasting and weak antinociceptive effect.

The B1 agonist, des‐Arg9‐BK (8 nmol) induced a significant antinociceptive effect, but this was not as intensive as that induced by BK.

The B2 antagonist D‐Arg0‐Hyp3‐Thi5, 8‐D‐Phe7‐BK (D‐Arg0) competitively antagonized the BK‐induced antinociception. Likewise, Hyp3‐Thi5, 8‐D‐Phe7‐BK (Hyp) also antagonized BK effect. However, the compound Thi5, 8‐D‐Phe7‐BK (Thi), initially considered a pure BK antagonist, induced an antinociceptive effect, supporting previous observations that this peptide can also act as a partial agonist.

It is concluded that the dose‐dependent antinociceptive effect induced by i.c.v. injection of BK is mediated by the stimulation of brain B2 receptors.
VIP‐ and PACAP‐mediated nonadrenergic, noncholinergic inhibition in longitudinal muscle of rat distal colon: involvement of activation of charybdotoxin‐ and apamin‐sensitive K+ channels
Authors: Kishi Masami , Takeuchi Tadayoshi , Suthamnatpong Naowarat , Ishii Toshiaki , Nishio Hideaki , Hata Fumiaki , Takewaki Tadashi
Published: July 2012

The mediators of nonadrenergic, noncholinergic (NANC) inhibitory responses in longitudinal muscle of rat distal colon were studied.

An antagonist of pituitary adenylate cyclase activating peptide (PACAP) receptors, PACAP6–38, concentration‐dependently inhibited the rapid relaxation of the longitudinal muscle induced by electrical field stimulation (EFS), resulting in a maximal inhibition of 47% at 3 μm.

PACAP6–38 inhibited the relaxation by 75% in the presence of the vasoactive intestinal peptide (VIP) receptor antagonist, VIP10–28 at μm, which inhibited the relaxation by 44%.

An antagonist of large conductance Ca2+‐activated K+ channels, charybdotoxin, concentration‐dependently inhibited the rapid relaxation of the longitudinal muscle, resulting in a maximal inhibition of 58% at 100 nM.

An antagonist of small conductance Ca2+‐activated K+ channels, apamin, concentration‐dependently inhibited the relaxation (58% at 1 μm).

Treatment with both K+ channel antagonists resulted in 84% inhibition of the EFS‐induced relaxation, which is comparable to the extent of inhibition induced by PACAP6–38 plus VIP10–28.

The inhibitory effect of VIP10–28 and of apamin, but not of charybdotoxin was additive: the same applied to PACAP6–38 and charybdotoxin, but not apamin.

Exogenously added VIP (100 nM‐1 μm) induced a slow gradual relaxation of the longitudinal muscle. Charybdotoxin, but not apamin significantly inhibited the VIP‐induced relaxation. VIP10–28, but not PACAP6–38 selectively inhibited the VIP‐induced relaxation.

Exogenously added PACAP (10–100 nM) also induced slow relaxation. Apamin and to a lesser extent, charybdotoxin, inhibited the PACAP‐induced relaxation. PACAP6–38, but not VIP10–28 selectively inhibited the PACAP‐induced relaxation.

Apamin at 100 nM inhibited inhibitory junction potentials (i.j.ps) induced by a single pulse of EFS. Apamin also inhibited a rapid phase, but not a delayed phase of i.j.ps induced by two pulses at 10 Hz. VIP10–28 did not inhibit i.j.ps induced by a single pulse, but significantly inhibited the delayed phase at two pulses. A combination of apamin and VIP10–28 abolished the i.j.ps induced by two pulses.

Both VIP and PACAP induced slow hyperpolarization of the cell membrane of the longitudinal muscle. Apamin inhibited the PACAP‐, but not VIP‐induced hyperpolarization.

From these findings it is suggested that VIP and PACAP are involved in NANC inhibitory responses of longitudinal muscle of the rat distal colon via activation of charybdotoxin‐ and apaminsensitive K+ channels, respectively.
Protection of low density lipoprotein oxidation at chemical and cellular level by the antioxidant drug dipyridamole
Authors: Iuliano L. , Colavita A.R. , Camastra C. , Bello V. , Quintarelli C. , Alessandroni M. , Piovella F. , Violi F.
Published: July 2012

The oxidative modification of low density lipoprotein (LDL) is thought to be an important factor in the initiation and development of atherosclerosis. Natural and synthetic antioxidants have been shown to protect LDL from oxidation and to inhibit atherosclerosis development in animals. Synthetic antioxidants are currently being tested, by they are not necessarily safe for human use.

We have previously reported that dipyridamole, currently used in clinical practice, is a potent scavenger of free radicals. Thus, we tested whether dipyridamole could affect LDL oxidation at chemical and cellular level.

Chemically induced LDL oxidation was made by Cu(II), Cu(II) plus hydrogen peroxide or peroxyl radicals generated by thermolysis of 2,2′‐azo‐6/s(2‐amidino propane). Dipyridamole, (1–10 μm), inhibited LDL oxidation as monitored by diene formation, evolution of hydroperoxides and thiobarbituric acid reactive substances, apoprotein modification and by the fluorescence of cis‐parinaric acid.

The physiological relevance of the antioxidant activity was validated by experiments at the cellular level where dipyridamole inhibited endothelial cell‐mediated LDL oxidation, their degradation by monocytes, and cytotoxicity.

In comparison with ascorbic acid, α‐tocopherol and probucol, dipyridamole was the more efficient antioxidant with the following order of activity: dipyridamole > probucol > ascorbic acid > α‐tocopherol. The present study shows that dipyridamole inhibits oxidation of LDL at pharmacologically relevant concentrations. The inhibition of LDL oxidation is unequivocally confirmed by use of three different methods of chemical oxidation, by several methods of oxidation monitoring, and the pharmacological relevance is demonstrated by the superiority of dipyridamole over the naturally occurring antioxidants, ascorbic acid and α‐tocopherol and the synthetic antioxidant probucol.
Interacting Effects of Translocation, Artificial Propagation, and Environmental Conditions on the Marine Survival of Chinook Salmon from the Columbia River, Washington, U.S.A.
Authors: HOLSMAN KIRSTIN K. , SCHEUERELL MARK D. , BUHLE ERIC , EMMETT ROBERT
Published: July 2012

Abstract:  Captive rearing and translocation are often used concurrently for species conservation, yet the effects of these practices can interact and lead to unintended outcomes that may undermine species’ recovery efforts. Controls in translocation or artificial‐propagation programs are uncommon; thus, there have been few studies on the interacting effects of these actions and environmental conditions on survival. The Columbia River basin, which drains 668,000 km2 of the western United States and Canada, has an extensive network of hydroelectric and other dams, which impede and slow migration of anadromous Pacific salmon (Oncorhynchus spp.) and can increase mortality rates. To mitigate for hydrosystem‐induced mortality during juvenile downriver migration, tens of millions of hatchery fish are released each year and a subset of wild‐ and hatchery‐origin juveniles are translocated downstream beyond the hydropower system. We considered how the results of these practices interact with marine environmental conditions to affect the marine survival of Chinook salmon (O. tshawytscha). We analyzed data from more than 1 million individually tagged fish from 1998 through 2006 to evaluate the probability of an individual fish returning as an adult relative to its rearing (hatchery vs. wild) and translocation histories (translocated vs. in‐river migrating fish that traveled downriver through the hydropower system) and a suite of environmental variables. Except during select periods of very low river flow, marine survival of wild translocated fish was approximately two‐thirds less than survival of wild in‐river migrating fish. For hatchery fish, however, survival was roughly two times higher for translocated fish than for in‐river migrants. Competition and predator aggregation negatively affected marine survival, and the magnitude of survival depended on rearing and translocation histories and biological and physical conditions encountered during their first few weeks of residence in the ocean. Our results highlight the importance of considering the interacting effects of translocation, artificial propagation, and environmental variables on the long‐term viability of species.
Ethnic Identity and Offending Trajectories Among Mexican American Juvenile Offenders: Gang Membership and Psychosocial Maturity
Authors: Knight George P. , Losoya Sandra H. , Cho Young Il , Chassin Laurie , Williams Joanna Lee , Cota‐Robles Sonia
Published: July 2012

We examined the association of joint trajectories of ethnic identity and criminal offending to psychosocial maturity, gang membership, andMexicanAmerican affiliation among 300MexicanAmerican male juvenile offenders from ages 14 to 22. There were two low‐offending groups: one was the highest in ethnic identity and changing slightly with age and the other was the lowest in ethnic identity and stable with age. A third group displayed moderately declining offending and moderately stable ethnic identity. A fourth group displayed high‐offending individuals with moderate, but increasing, levels of ethnic identity, who were initially lower in psychosocial maturity and more likely to be gang members. The findings highlight the need to contextualize theories of ethnic identity development.
Multiple mating by females is a natural outcome of a null model of mate encounters
Authors: Kokko Hanna , Mappes Johanna
Published: July 2012

Why do females of so many species mate multiply? The question makes use of an implicit null model that females by default should be monandrous and that polyandry requires an explanation. Here, we make the simple point that females encounter mates over their lifetime in a stochastic manner, and as they should accept at least one male, acceptance of all males may be a better null model than the more advanced strategy of accepting the first satisfactory one and rejecting all others. The advantage of this view is that it makes it explicit that females must accept and reject mates without precise knowledge of future mate encounters. In insects, for example, limitations of cognitive and sensory capabilities make it hard for females to compare many potential mates simultaneously. It is then not always possible for a female to be very choosy (i.e., to reject a large proportion of encounters) without simultaneously increasing the expected time spent as a virgin and decreasing the overall expected number of mates she accrues during her lifetime. We show that this fact easily leads to a pattern where choosiness is reduced and most females mate with more males than their optimal mate number. Our results suggest that monandry and polyandry may be less distinct strategies than they first appear as they may, to a large extent, reflect chance events influencing mate encounters. Polyandry can arise as a side effect of avoiding the risk of encountering too few acceptable mates – a viewpoint that is easily missed if females that have remained unmated are not included in datasets.
A multiresistant clone of Pseudomonas aeruginosa sequence type 773 spreading in a burn unit in Orumieh, Iran
Authors: Yousefi Saber , Nahaei Mohammad Reza , Farajnia Safar , Aghazadeh Mohammad , Iversen Aina , Edquist Petra , Maãtallah Makaoui , Giske Christian G.
Published: July 2012

Herein, we describe the phenotypic and genotypic characterization of a multiresistant clone of Pseudomonas aeruginosa disseminating in a burn unit in Orumieh, Iran. A total of 58 isolates of P. aeruginosa were collected during August 2007 and June 2008. Minimum inhibitory concentrations (MICs) of P. aeruginosa isolates were determined against 11 antimicrobial agents by E test. Serotyping, pulsed‐field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were used for studying the clonal relationship among the isolates. Antibiotic susceptibility testing revealed that most of the isolates were multidrug resistant and colistin was the antibiotic with the highest activity. Pseudomonas aeruginosa isolates fell into nine different serotypes, and O10 and O11 were the most common. PFGE analyses showed 12 different genotypes and 68.1% of isolates showed more than 80% similarity, indicating possible clonal relatedness. These isolates were found to belong to the same sequence type, ST773. This sequence type has earlier been reported from China, and a double locus variant of this ST has been found earlier in France in a PER‐1 extended‐spectrum β‐lactamase‐producing P. aeruginosa.
Hierarchical effects of environmental filters on the functional structure of plant communities: a case study in the French Alps
Authors: Bello Francesco de , Lavorel Sandra , Lavergne Sébastien , Albert Cécile H. , Boulangeat Isabelle , Mazel Florent , Thuiller Wilfried
Published: July 2012

Understanding the influence of the environment on the functional structure of ecological communities is essential to predict the response of biodiversity to global change drivers. Ecological theory suggests that multiple environmental factors shape local species assemblages by progressively filtering species from the regional species pool to local communities. These successive filters should influence the various components of community functional structure in different ways. In this paper, we tested the relative influence of multiple environmental filters on various metrics of plant functional trait structure (i.e. ‘community weighted mean trait’ and components of functional trait diversity, i.e. functional richness, evenness and divergence) in 82 vegetation plots in the Guisane Valley, French Alps. For the 211 sampled species we measured traits known to capture key aspects of ecological strategies amongst vascular plant species, i.e. leaf traits, plant height and seed mass (LHS). A comprehensive information theory framework, together with null model based resampling techniques, was used to test the various environmental effects. Particular community components of functional structure responded differently to various environmental gradients, especially concerning the spatial scale at which the environmental factors seem to operate. Environmental factors acting at a large spatial scale (e.g. temperature) were found to predominantly shape community weighted mean trait values, while fine‐scale factors (topography and soil characteristics) mostly influenced functional diversity and the distribution of trait values among the dominant species. Our results emphasize the hierarchical nature of ecological forces shaping local species assemblage: large‐scale environmental filters having a primary effect, i.e. selecting the pool of species adapted to a site, and then filters at finer scales determining species abundances and local species coexistence. This suggests that different components of functional community structure will respond differently to environmental change, so that predicting plant community responses will require a hierarchical multi‐facet approach.
The Dialogue of Religious Experience: Theory and Practice
Authors: Friday John R.
Published: July 2012

For several decades the official teaching office of the Roman Catholic Church has consistently invoked the notion of religious experience as a category for interrelgious dialogue. Moreover, the Church has appealed to the so-called dialogue of religious experience as a means of encouraging its members to constructively engage with persons who are committed to ‘other’ religious traditions. This essay seeks to develop a systematic understanding of religious experience as well as the dialogue associated with it. Subsequent to summarizing the recent magisterial teaching on the dialogue of religious experience, the essay continues by probing the meaning of religious experience as such, particularly with the assistance of the theological insights of Bernard Lonergan and Louis Roy. The essay concludes by acknowledging some of the limitations that persist in connection with the dialogue of religious experience, namely, those that inevitably arise when considering the particularity of the incarnation and the necessity of the Church for salvation.
INTERCULTURALISM, MULTICULTURALISM, AND THE STATE FUNDING AND REGULATION OF CONSERVATIVE RELIGIOUS SCHOOLS
Authors: Maxwell Bruce , Waddington David I. , McDonough Kevin , Cormier Andrée‐Anne , Schwimmer Marina
Published: July 2012

In this essay, Bruce Maxwell, David Waddington, Kevin McDonough, Andrée‐Anne Cormier, and Marina Schwimmer compare two competing approaches to social integration policy, Multiculturalism and Interculturalism, from the perspective of the issue of the state funding and regulation of conservative religious schools. After identifying the key differences between Interculturalism and Multiculturalism, as well as their many similarities, the authors present an explanatory analysis of this intractable policy challenge. Conservative religious schooling, they argue, tests a conceptual tension inherent in Multiculturalism between respect for group diversity and autonomy, on the one hand, and the ideal of intercultural citizenship, on the other. Taking as a case study Québec's education system and, in particular, recent curricular innovations aimed at helping young people acquire the capabilities of intercultural citizenship, the authors illustrate how Interculturalism signals a compelling way forward in the effort to overcome the political dilemma of conservative religious schooling.
The Contemporary Presidency: The Personnel Process in the Modern Presidency
Authors: LEWIS DAVID E.
Published: July 2012

During a presidential election year, public attention naturally turns toward candidates and campaigns. The best prepared candidates, however, are thinking beyond voting day toward postelection planning. The task of transitioning to become president is enormous. On the personnel side, a new president will have to fill between 3,000 and 4,000 positions. In this article I review the current state of presidential personnel politics. I review the choices confronting presidents and how the personnel process is changing. I conclude by making suggestions for reforming the personnel system equally applicable to either party's candidate for the presidency in 2012.
The Law: Can the President Recess Appoint a Vice President?
Authors: BROWNELL II ROY E.
Published: July 2012

If a vice president dies, resigns, is removed, or his position is otherwise vacated, and if Congress is out of session, does the president have the authority to fill the vacancy through a recess appointment, or is his only means of installing a new vice president through the bicameral confirmation process under the Twenty‐Fifth Amendment? This article evaluates this novel constitutional question, which is important in light of the vice presidency's increased prominence in recent years, the expansion of presidential recess appointment power over the course of the nation's history, and the greater frequency with which presidents have carried out these unilateral actions in past decades. While arguments in favor of the president cannot be dismissed out of hand, ultimately it must be concluded that he lacks such power.
The Immobilization of Polyethylene Imine Nano and Microspheres on Glass Using High Intensity Ultrasound
Authors: Shimanovich Ulyana , Cavaco‐Paulo Artur , Gedanken Aharon
Published: July 2012

The present article describes the creation and immobilization of Polyethylene imine (PEI) capsules on a glass surface. The synthesis and deposition were accomplished by short‐time (3 min) one‐step reaction. The preparation and immobilization of PEI spheres, was carried out using an environmental friendly method, the ultrasonic emulsification. The ultrasonic technique enables to control size and fulfillment of the internal part of the immobilized PEI spheres. Moreover, the ultrasonic emulsification method showed 100% efficiency in PEI spheres creation, which means no residues of aqueous PEI and oil solvents remained in the reaction flask after the nanosphere's creation. The immobilized PEI spheres have sizes varied from 50 to 500 nm. The PEI spheres were successfully filled either with organic solvent (hydrophobic) or with water (hydrophilic). This method provides us the perspective for future encapsulation of varies molecules which have hydrophobic or hydrophilic nature.
Fully Protected Glycosylated Zinc (II) Phthalocyanine Shows High Uptake and Photodynamic Cytotoxicity in MCF‐7 Cancer Cells
Authors: Kimani Stanley G. , Shmigol Tatiana A. , Hammond Samantha , Phillips James B. , Bruce James I. , MacRobert Alexander J. , Malakhov Mikhail V. , Golding Jon P.
Published: July 2012

Phthalocyanine photosensitizers are effective in anticancer photodynamic therapy (PDT) but suffer from limited solubility, limited cellular uptake and limited selectivity for cancer cells. To improve these characteristics, we synthesized isopropylidene‐protected and partially deprotected tetra β‐glycosylated zinc (II) phthalocyanines and compared their uptake and accumulation kinetics, subcellular localization, in vitro photocytotoxicity and reactive oxygen species generation with those of disulfonated aluminum phthalocyanine. In MCF‐7 cancer cells, one of the compounds, zinc phthalocyanine {4}, demonstrated 10‐fold higher uptake, 5‐fold greater PDT‐induced cellular reactive oxygen species concentration and 2‐fold greater phototoxicity than equimolar (9 μm) disulfonated aluminum phthalocyanine. Thus, isopropylidene‐protected β‐glycosylation of phthalocyanines provides a simple method of improving the efficacy of PDT.
Neural Mechanisms of Rhythm Perception: Current Findings and Future Perspectives
Authors: Grahn Jessica A.
Published: July 2012

Perception of temporal patterns is fundamental to normal hearing, speech, motor control, and music. Certain types of pattern understanding are unique to humans, such as musical rhythm. Although human responses to musical rhythm are universal, there is much we do not understand about how rhythm is processed in the brain. Here, I consider findings from research into basic timing mechanisms and models through to the neuroscience of rhythm and meter. A network of neural areas, including motor regions, is regularly implicated in basic timing as well as processing of musical rhythm. However, fractionating the specific roles of individual areas in this network has remained a challenge. Distinctions in activity patterns appear between “automatic” and “cognitively controlled” timing processes, but the perception of musical rhythm requires features of both automatic and controlled processes. In addition, many experimental manipulations rely on participants directing their attention toward or away from certain stimulus features, and measuring corresponding differences in neural activity. Many temporal features, however, are implicitly processed whether attended to or not, making it difficult to create controlled baseline conditions for experimental comparisons. The variety of stimuli, paradigms, and definitions can further complicate comparisons across domains or methodologies. Despite these challenges, the high level of interest and multitude of methodological approaches from different cognitive domains (including music, language, and motor learning) have yielded new insights and hold promise for future progress.