bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractIn 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

AbstractThe 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

AbstractBinding 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

AbstractBackgroundThe 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.AimsTo 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.MethodsTwelve 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.ResultsDiclofenac 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.ConclusionThe 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.
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.