bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemical model for superconductivity
Authors: Larsson Sven 
Published: November 2002

AbstractA “chemical” model based on the theory of mixed valence systems is successful in explaining a number of properties of superconductors. The model is formulated in configuration space but is consistent with Bardeen–Cooper–Schrieffer theory, and connects directly to chemical properties that may be calculated by quantum chemical methods. Crystal structure is important, in particular the difference in equilibrium geometry between different oxidation states. According to the model, high pressure causes less difference between the oxidation states and hence a lower, or possibly disappearing, activation barrier and increased conductivity. This agrees with the experiments. Mixed valence systems with nonequivalent sites or with a large structural difference between the oxidation states are not superconducting or even conducting. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002
Unique changes in synaptic morphology following tetanization under pharmacological blockade
Authors: Weeks Andrew C.W. , Ivanco Tammy L. , Leboutillier Janelle C. , Marrone Diano F. , Racine Ronald J. , Petit Ted L. 
Published: November 2002

AbstractLong‐term potentiation (LTP) in the hippocampus has been associated with changes in synaptic morphology. Whether these changes are LTP‐dependent or simply a result of electrophysiological stimulation has not yet been fully determined. This study involved an examination of synaptic morphology in the rat dentate gyrus 24 h after electrophysiological stimulation sufficient to induce LTP. In one group, ketamine, a competitive NMDA antagonist, was injected prior to stimulation to block the formation of LTP. Synaptic morphological quantification included estimating the total number of synapses per neuron, determining synaptic curvature and the presence of synaptic perforations, and measuring the maximal PSD profile length of the synapses. The results indicated that most of the changes observed following the induction of LTP (increases in the proportion of concave‐shaped synapses, increases in perforated concave synapses, and a decrease in the length of nonperforated concave synapses) are not observed under ketamine blockade, suggesting that they are LTP‐specific and not simply the result of tetanic stimulation. Ketamine was associated, however, with several novel structural changes including a decrease in the length of the perforations in the concave perforated synapses, a reduction in the number of convex perforated synapses, and a nonlayer‐specific increase in synaptic length compared to controls. Based on previous research, this combination of morphological characteristics is potentially less efficacious, which suggests that synapses that are tetanized but not potentiated, due to pharmacological blockade, appear to undergo opposing, compensatory, or homeostatic changes. These results support the suggestion that synaptic morphology changes are both stimulation‐ and area‐specific, are highly complex, and depend on the specific local physiology. Synapse 47:77–86, 2003. © 2002 Wiley‐Liss, Inc.
Estimating the number of release sites and probability of firing within the nerve terminal by statistical analysis of synaptic charge
Authors: Viele Kert , Stromberg Arnold J. , Cooper Robin L. 
Published: November 2002

AbstractInvestigating the function of individual synapses is essential to understanding the mechanisms that influence the efficacy of chemical synaptic transmission. The known simplicity of the synaptic structure at the crayfish neuromuscular junction (NMJ) and its quantal nature of release allows an assessment of discrete synapses within the motor nerve terminals. Our goal in this article is to investigate the effect of the stimulation frequency on the number of active release sites (n) and the probability of release (p) at those active sites. Because methods based on direct counts often provide unstable joint estimates of (n) and (p), we base our analysis on mixture modeling. In particular, the mixture modeling approach is used to estimate (n) and (p) for stimulation frequencies of 1 Hz, 2 Hz, and 3 Hz. Our results indicate that as the stimulation frequency increases, new sites are recruited (thus increasing n) and the probability of release (p) increases. Synapse 47:15–25, 2003. © 2002 Wiley‐Liss, Inc.
The antihistamine fexofenadine does not affect IKr currents in a case report of drug‐induced cardiac arrhythmia
Authors: Scherer Constanze R , Lerche Christian , Decher Niels , Dennis Adrienne T , Maier Patrick , Ficker Eckhard , Busch Andreas E , Wollnik Bernd , Steinmeyer Klaus 
Published: November 2002

The human HERG gene encodes the cardiac repolarizing K+ current IKr and is genetically inactivated in inherited long QT syndrome 2 (LQTS2). The antihistamine terfenadine blocks HERG channels, and can cause QT prolongation and torsades de pointes, whereas its carboxylate fexofenadine lacks HERG blocking activity.
In the present study the ability of fexofenadine to block the K897T HERG channel variant was investigated. The underlying single nucleotide polymorphism (SNP) A2960C was identified in a patient reported to develop fexofenadine‐associated LQTS.
K897T HERG channels produced wild‐type‐like currents in Xenopus oocytes. Even at a concentration of 100 μM, fexofenadine did not inhibit wild‐type or K897T HERG channels. Coexpression of wild‐type and K897T HERG with the ß‐subunit MiRP1, slightly changed current kinetics but did not change sensitivity to terfenadine and fexofenadine.
Western blot analysis and immunostaining of transiently transfected COS‐7 cells demonstrated that overall expression level, glycosylation pattern and subcellular localization of K897T HERG is indistinguishable from wild‐type HERG protein, and not altered in the presence of 1 μM fexofenadine.
We provide the first functional characterization of the K897T HERG variant. We demonstrated that K897T HERG is similar to wild‐type HERG, and is insensitive to fexofenadine. Although the polymorphism changes PKA and PKC phosphorylation sites, regulation of K897T HERG by these kinases is not altered.
Our results strongly indicate that QT lengthening and cardiac arrhythmia in the reported case of drug‐induced LQT are not due to the K897T exchange or to an inhibitory effect of fexofenadine on cardiac IKr currents.

British Journal of Pharmacology (2002) 137, 892–900. doi:10.1038/sj.bjp.0704873
Contractile responses to adenosine, R‐PIA and ovalbumen in passively sensitized guinea‐pig isolated airways
Authors: Martin Timothy J , Broadley Kenneth J 
Published: November 2002

Responses to adenosine, R‐PIA and ovalbumen were examined in guinea‐pig isolated superfused tracheal spirals to determine the effects of passive sensitization by overnight incubation in serum from ovalbumen (OA)‐sensitized or non‐sensitized guinea‐pigs.
Tissues incubated with serum from non‐sensitized and OA‐sensitized guinea‐pigs contracted (0.07±0.02 and 0.04±0.01 g, respectively) to adenosine (300 μM) whereas non‐incubated or Krebs‐incubated tissues produced no contractions to adenosine or ovalbumen (10 μg). Ovalbumen caused substantial contractions (0.40±0.09 g) after OA‐sensitized serum incubation and significantly (P<0.05) smaller contractions (0.08±0.03 g) after non‐sensitized serum incubation. Tracheae from guinea‐pigs actively sensitized to ovalbumen 14–21 days beforehand also contracted to adenosine, R‐PIA (3 μM) and ovalbumen.
The A1/A2 adenosine receptor antagonist, 8‐phenyltheophylline (8‐PT, 3 μM), failed to antagonize these contractions, suggesting that A1/A2 adenosine receptors were not involved.
Unlike adenosine, R‐PIA (3 μM) produced contractions in non‐incubated (0.23±0.04 g) or Krebs‐incubated (0.15±0.04 g) tracheae, as well as after passive and active sensitization. None of these responses were blocked by 8‐PT.
The A3 receptor agonist, IB‐MECA, in the presence of 8‐PT produced small contractions in passively sensitized tracheae (10 μM, 0.02±0.003 g) and, in larger doses (100 μM and 1 mM), contracted actively sensitized tracheae.
In actively sensitized trachea, the A3 receptor antagonist, MRS‐1220 (100 nM), significantly (P<0.05) attenuated adenosine contractions in the presence of 8‐PT from 0.23±0.07 g to 0.07±0.03 g.
These results show that passive, like active sensitization, reveals bronchoconstrictions to adenosine of isolated tracheae. The insensitivity to 8‐PT blockade, the antagonism by MRS‐1220, and the fact that the A3 receptor agonist, IB‐MECA, mimics this response, suggest involvement of A3 receptors. R‐PIA, however, has a different profile of adenosine receptor activity.

British Journal of Pharmacology (2002) 137, 729–738. doi:10.1038/sj.bjp.0704902
Leptin potentiates IFN‐γ‐induced expression of nitric oxide synthase and cyclo‐oxygenase‐2 in murine macrophage J774A.1
Authors: Raso Giuseppina Mattace , Pacilio Maria , Esposito Emanuela , Coppola Anna , Di Carlo Raffaele , Meli Rosaria 
Published: November 2002

Leptin, a pleiotropic hormone believed to regulate body weight, has recently been associated with inflammatory states and immune activity. Here we have studied the effect of leptin on expression of IFN‐γ‐induced nitric oxide synthase (iNOS) and cyclo‐oxygenase‐2 (COX‐2), both prominent markers of macrophage activation, using the murine macrophage J774A.1 cell line.
After 24 h of incubation, leptin (1–10 μg ml−1) potently synergized with IFN‐γ (100 U ml−1) in nitric oxide (NO) release, evaluated as nitrite and nitrate (NOx), and prostaglandin E2 (PGE2) production in culture medium.
The observed increase of NO and PGE2 was related to enhanced expression of the respective inducible enzyme isoforms, measured in mRNA and protein by RT–PCR and Western blot analysis, respectively.
When cells were stimulated only with leptin, a weak induction of NO and PGE2 release and of the expression of related inducible enzymes was observed.
Moreover IFN‐γ increased the expression of the functional form of leptin receptor (Ob‐Rb) and this effect was potentiated by leptin in a concentration‐dependent manner.
These data suggest that macrophages, among the peripheral immune cells, represent a target for leptin and confirm the relevance of this hormone in the pathophysiology of inflammation.

British Journal of Pharmacology (2002) 137, 799–804. doi:10.1038/sj.bjp.0704903
Cyclosporine A regulate oxidative stress‐induced apoptosis in cardiomyocytes: mechanisms via ROS generation, iNOS and Hsp70
Authors: Chen Huei‐Wen , Chien Chiang‐Ting , Yu Sung‐Liang , Lee Yuan‐Teh , Chen Wen‐Jone 
Published: November 2002

Previous study suggested that cyclosporine A (CsA) could partially reduce ischaemia/reperfusion‐induced injury in isolated heart, but the mechanism was still unclear. In this study, the possible mechanisms of cyclosporine A in regulating oxidative stress‐induced cardiomyocyte apoptosis were examined.
Morphological (cell shrinkage, apoptotic body formation, and DNA fragmentation) and biochemical (annexin‐V staining for exposed phosphatidylserine residues) evidences showed that both hydrogen peroxide (H2O2) and hypoxia/reoxygenation could induce apoptotic change in the embryonal rat heart myoblast‐derived cells (H9c2). These effects were inhibited by pre‐treatment with CsA at concentration of 0.01–1.0 μM for 24 h, but were increased with 10.0 μM CsA.
While examining the mechanisms of CsA in protecting cardiomyocyte apoptosis, we found that the collapse of mitochondria membrane potential (ΔΨm) induced by oxidative stress was partially reversed by CsA (0.01–1.0 μM).
Compared to the control, CSA at the concentration of 0.1 and 10.0 μM significantly increased the level of intracellular reactive oxygen species (ROS) to 117.2±12.4% and 234.4±9.3%, respectively. Co‐incubating with the antioxidant, ascorbic acid (10.0 μM), could partially reduce the protective effect of CsA (0.01–1.0 μM) and the toxic effect of 10.0 μM CsA.
Pre‐treatment with CsA at concentration of 0.01–1.0 μM for 24 h produced up‐regulation of heat shock protein 70 (Hsp 70), inducible nitric oxide synthase (iNOS) and also induced NO production, indicating that these factors might be associated with the cell protective effects of CsA.
These results suggest that CsA could protect the oxidative stress‐induced cardiomyocyte apoptosis not only by preventing the loss of ΔΨm in mitochondria, but also through ROS generation, Hsp70, and iNOS up‐regulation.

British Journal of Pharmacology (2002) 137, 771–781. doi:10.1038/sj.bjp.0704908
Differential effects of organic calcium‐channel blockers on diastolic SR calcium‐handling in the frog heart
Authors: Subramani Sathya , Vijayanand Caroline , Tharion Elizabeth 
Published: November 2002

Gradual loss of sarcoplasmic reticular (SR) calcium during a rest‐period is responsible for the rest‐induced decay (RID) of force in mammalian myocardium. Effect of verapamil and diltiazem on a similar RID in the frog myocardium suggests a new mechanism of action of these drugs.
Strips of frog‐ventricle were paced at 0.2 Hz and the rhythm was interrupted by varying rest‐periods ranging from 10 to 180 s. In control conditions, the amplitude of the post‐rest beat was significantly lower than that of the pre‐rest beat for rest‐periods more than 40 s (RID).
Verapamil and diltiazem (which are organic calcium‐channel blockers (OCCB)) changed the pattern of RID in the control solution to a ‘rest‐induced potentiation’ (RIP) in the same preparation while another OCCB nifedipine and the inorganic calcium‐channel blocker cadmium did not alter the post‐rest phenomenon.
We propose that verapamil and diltiazem produce an RIP due to either blockade of SR calcium‐leak during rest or enhancement of SR calcium‐uptake during rest.

British Journal of Pharmacology (2002) 137, 756–760. doi:10.1038/sj.bjp.0704921
Gingerols: a novel class of vanilloid receptor (VR1) agonists
Authors: Dedov Vadim N , Tran Van H , Duke Colin C , Connor Mark , Christie MacDonald J , Mandadi Sravan , Roufogalis Basil D 
Published: November 2002

Gingerols, the pungent constituents of ginger, were synthesized and assessed as agonists of the capsaicin‐activated VR1 (vanilloid) receptor.
[6]‐Gingerol and [8]‐gingerol evoked capsaicin‐like intracellular Ca2+ transients and ion currents in cultured DRG neurones. These effects of gingerols were blocked by capsazepine, the VR1 receptor antagonist.
The potency of gingerols increased with increasing size of the side chain and with the overall hydrophobicity in the series.
We conclude that gingerols represent a novel class of naturally occurring VR1 receptor agonists that may contribute to the medicinal properties of ginger, which have been known for centuries. The gingerol structure may be used as a template for the development of drugs acting as moderately potent activators of the VR1 receptor.

British Journal of Pharmacology (2002) 137, 793–798. doi:10.1038/sj.bjp.0704925
Inhibitory mechanism of vascular endothelial growth factor (VEGF) by bucillamine
Authors: Koyama Shinji , Takagi Hitoshi , Otani Atsushi , Oh Hideyasu , Nishimura Kazuo , Honda Yoshihito 
Published: November 2002

Vascular endothelial growth factor (VEGF) plays an important role in the neovascularization of ischaemic retinal diseases such as proliferative diabetic retinopathy. We determined that bucillamine, an anti‐rheumatic drug, inhibits the VEGF production induced by hypoxia in bovine retinal microcapillary endothelial cells (BREC). To further clarify the inhibitory mechanism, we investigated the possible mechanism by which bucillamine exerts this inhibitory effect.
Bucillamine (100 μM) decreased the hypoxia‐induced increase of VEGF mRNA by 54.5% (P<0.001). Bucillamine (100 μM) reduced the hypoxia‐induced VEGF content in culture media by 29.0% (P<0.001), while monosulfydryl drugs, N‐acetylcysteine and D‐penicillamine, did not.
Bucillamine (100 μM) did not affect VEGF mRNA half‐life (hypoxia, 4.3 h; hypoxia+bucillamine, 3.9 h; normoxia, 2.7 h; normoxia+bucillamine, 2.7 h).
Reporter gene studies revealed that bucillamine reduced transcriptional activity in the 5′‐flanking region of the VEGF gene by 74.0%. Hypoxia stimulated binding activity of BREC nuclear protein to a hypoxia responsive element (HRE), which was decreased by bucillamine.
Bucillamine inhibited hypoxic‐induction of HIF‐1α mRNA by 73.1% (P<0.001). Bucillamine also inhibited spontaneous VEGF mRNA expression by 26.6%. Furthermore, it inhibited activity of VEGF promoter and decreased binding activity to Sp1 and HRE, but did not alter AP1 and AP2 activity in normoxia.
These data suggest that bucillamine inhibits hypoxic induction of VEGF through inhibition of HIF‐1 induction and binding activity in BREC. Bucillamine also inhibits the spontaneous expression of VEGF mRNA by its effect on Sp1 and HRE binding.

British Journal of Pharmacology (2002) 137, 901–909. doi:10.1038/sj.bjp.0704929
Zebrafish M2 muscarinic acetylcholine receptor: cloning, pharmacological characterization, expression patterns and roles in embryonic bradycardia
Authors: Hsieh Dennis Jine‐Yuan , Liao Ching‐Fong 
Published: November 2002

A zebrafish M2 muscarinic acetylcholine receptor (mAChR) gene was cloned. It encodes 495 amino acids in a single exon. The derived amino acid sequence is 73.5% identical to its human homologue.
Competitive binding studies of the zebrafish M2 receptor and [3H]‐NMS gave negative log dissociation constants (pKi) for each antagonist as follows: atropine (9.16)>himbacine (8.05)4‐DAMP (7.83)>AF‐DX 116 (7.26)pirenzepine (7.18)tropicamide (6.97)methoctramine (6.82)p‐F‐HHSiD (6.67)>carbachol (5.20). The antagonist affinity profile correlated with the profile of the human M2 receptor, except for pirenzepine.
Reverse transcription polymerase chain reaction and Southern blotting analysis demonstrated that the M2 mAChR mRNA levels increased during the segmentation period (12 h post‐fertilization; h.p.f.) in zebrafish. By whole‐mount in situ hybridization, the M2 mAChR was first detectable in the heart, vagus motor ganglion, and vagus sensory ganglion at 30, 48 and 60 h.p.f., respectively.
The muscarinic receptor that mediates carbachol (CCh)‐induced bradycardia was functionally mature at 72 h.p.f. The effect of CCh‐induced bradycardia was antagonized by several muscarinic receptor antagonists with the order of potency (pIC50 values): atropine (6.76)>methoctramine (6.47)>himbacine (6.10)>4‐DAMP (5.72)>AF‐DX 116 (4.77), however, not by pirenzepine, p‐F‐HHSiD, or tropicamide (<10 μM).
The effect of CCh‐induced bradycardia was abolished completely before 56 h.p.f. by M2 RNA interference, and the bradycardia effect gradually recovered after 72 h.p.f. The basal heart rate was increased in embryos injected with M2 mAChR morpholino antisense oligonucleotide (M2 MO) and the effect of CCh‐induced bradycardia was abolished by M2 MO in a dose‐dependent manner. In conclusion, the results suggest that the M2 mAChR inhibit basal heart rate in zebrafish embryo and the M2 mAChR mediates the CCh‐induced bradycardia.

British Journal of Pharmacology (2002) 137, 782–792. doi:10.1038/sj.bjp.0704930
Respiratory actions of vanilloid receptor agonists in the nucleus of the solitary tract: comparison of resiniferatoxin with non‐pungent agents and anandamide
Authors: Geraghty Dominic P , Mazzone Stuart B 
Published: November 2002

Activation of vanilloid receptors on sensory nerve terminals in the commissural nucleus of the solitary tract (cNTS) of rats with capsaicin, produces respiratory slowing. In this study, we used microinjection techniques employing pungent and non‐pungent vanilloids to further characterize vanilloid receptors in the cNTS.
Microinjection of the pungent vanilloid, resiniferatoxin (RTX), into the cNTS of urethane‐anaesthetized rats, dose‐dependently reduced respiratory rate without affecting tidal volume. RTX was 20 fold more potent at slowing respiration (∼ED50, 100 pmol) than capsaicin (∼ED50, 2 nmol). Doses of RTX greater than 100 pmol caused either irregular (dyspnoeic) breathing or terminal apnoea (>250 pmol). The respiratory slowing response to RTX (75 pmol), was dose‐dependently attenuated by injecting RTX (but not vehicle) into the same site 60 min earlier.
The non‐pungent phorbol derivative of RTX, phorbol 12‐phenylacetete 13‐acetate 20‐homovanillate (PPAHV, 0.1–1 nmol), also slowed respiration (ED50, ∼1 nmol) and almost abolished response to RTX (75 pmol) injected into the same site 60 min later.
In contrast to RTX, PPAHV and capsaicin, the putative endogenous vanilloid receptor agonist, arachidonyl ethanolamide (AEA), and non‐pungent capsaicin derivative, olvanil, had no direct effect on respiration. However, both AEA and olvanil dose‐dependently reduced the respiratory response to injection of RTX (75 pmol) 60 min later into the same site (EC50s, for AEA and olvanil, ∼2 and 0.2 nmol, respectively).
These studies suggest that both pungent and non‐pungent vanilloids interact with vanilloid receptors in the cNTS. However, whereas RTX and PPAHV activate and subsequently desensitize vanilloid receptors on sensory nerve terminals in the cNTS, olvanil and AEA fail to activate despite readily desensitizing responses to RTX in this region.

British Journal of Pharmacology (2002) 137, 919–927. doi:10.1038/sj.bjp.0704931
Mechanism of lonidamine inhibition of the CFTR chloride channel
Authors: Gong Xiandi , Burbridge Susan M , Lewis Angie C , Wong Patrick Y D , Linsdell Paul 
Published: November 2002

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel is blocked by a broad range of organic anionic compounds. Here we investigate the effects of the indazole compound lonidamine on CFTR channels expressed in mammalian cell lines using patch clamp recording.
Application of lonidamine to the intracellular face of excised membrane patches caused a voltage‐dependent block of CFTR currents, with an apparent Kd of 58 μM at −100 mV.
Block by lonidamine was apparently independent of channel gating but weakly sensitive to the extracellular Cl− concentration.
Intracellular lonidamine led to the introduction of brief interruptions in the single channel current at hyperpolarized voltages, leading to a reduction in channel mean open time. Lonidamine also introduced a new component of macroscopic current variance. Spectral analysis of this variance suggested a blocker on rate of 1.79 μM−1 s−1 and an off‐rate of 143 s−1.
Several point mutations within the sixth transmembrane region of CFTR (R334C, F337S, T338A and S341A) significantly weakened block of macroscopic CFTR current, suggesting that lonidamine enters deeply into the channel pore from its intracellular end.
These results identify and characterize lonidamine as a novel CFTR open channel blocker and provide important information concerning its molecular mechanism of action.

British Journal of Pharmacology (2002) 137, 928–936. doi:10.1038/sj.bjp.0704932