bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyaluronidase versus Foley catheter for cervical ripening in high‐risk term and post term pregnancies
Authors: Surita F.G.C. , Cecatti J.G. , Parpinelli M.A. , Krupa F. , Pinto e Silva J.L.
Published: January 2005

Objective

To evaluate the effectiveness and safety of Foley catheter and hyaluronidase for cervical ripening.

Method

Randomized controlled trial where 140 pregnant women, with gestational age ≥37 weeks, indication for labor induction and an unripe cervix, were enrolled, allocated in two groups according to the method of cervical ripening before labor induction. Statistical analysis used Student's t‐test, Mann–Whitney, Chi‐square test, survival analysis, risk ratios and number needed to treat.

Results

Time of induction, dose of oxytocin and mode of delivery had better results in the Foley catheter group. Comfort with the method was higher in the hyaluronidase group.

Conclusions

Both methods were effective and safe for cervical ripening. The Foley catheter group experienced a shorter period of induction, required a lower dose of oxytocin and had higher vaginal delivery rates, while the women who used hyaluronidase declared greater comfort with the method.
Strain and excursion in the rat sciatic nerve during a modified straight leg raise are altered after traumatic nerve injury
Authors: Boyd Benjamin S. , Puttlitz Christian , Gan Jerylin , Topp Kimberly S.
Published: January 2005

Purpose: This study investigated the biomechanics of the sciatic nerve with hind limb positioning in live and euthanized Sprague‐Dawley rats after traumatic nerve injury.

Methods: With radiographic analysis, sciatic nerve excursion and strain were measured in situ during a modified straight leg raise, which included sequential hip flexion and ankle dorsiflexion. Comparisons were made between nerves in uninjured, sham‐injured and mild crush‐injured rats at the 7‐day and 21‐day recovery times.

Results: Significant strain and proximal excursion of the sciatic nerve were observed in all groups during hip flexion, and additional increased strain was noted during dorsiflexion. Seven days after nerve injury, strain increased significantly during hip flexion (17.64 ± 14.12%;p = 0.0091) and dorsiflexion (22.56 ± 15.47%;p = 0.0082) compared to the sham‐injured controls. At 21 days after injury, the strains were similar between the injured and sham‐injured groups.

Conclusions: Nerve bed elongation during straight leg raise causes sciatic nerve strain and excursion towards the moving joint with the greatest movement nearest the moving joint. In the first week after injury, the maximal strain exceeded the level previously shown to impair nerve conduction and circulation. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Relational hierarchies in Optimality Theory: the case of syllable contact
Authors: Gouskova Maria
Published: January 2005

A number of phonological laws require adjacent elements to stand a certain distance apart from each other on some prominence scale. For example, according to the Syllable Contact Law, the greater the sonority slope between the coda and the following onset, the better. Languages such as Faroese, Icelandic, Sidamo, Kazakh and Kirghiz select different thresholds for an acceptable sonority slope. This article proposes a theory for deriving hierarchies of relational constraints such as the Syllable Contact Law from prominence scales in the constraint set CON in Optimality Theory. The proposal is compared to two alternative approaches, non-hierarchical constraints and the local conjunction of constraint hierarchies, which are argued to make undesirable empirical and theoretical predictions.
A tonal analysis of Cologne Schärfung
Authors: Gussenhoven Carlos , Peters Jörg
Published: January 2005

The word prosody of the dialect of Cologne includes a phonological contrast in stressed syllables which at first sight might either reflect a ternary quantity contrast or a binary quantity contrast plus a tone contrast. There are differences in duration as well as F0 between Accent 1 (Schärfung) and Accent 2, along with differences in the intensity profiles of the syllables. It is argued that the contrast is one between an unspecified lexical tone (T) (Accent 2) and no tone (Accent 1), and that the lexical tone assimilates to an intonational tone. We show that a ternary quantity contrast (i) cannot capture the difference between Accent 1 and Accent 2; (ii) would imply an otherwise unattested distributional confinement to the syllable coda of geminate consonants and (iii) would imply unexpected intonation contours in bimoraic syllables. By contrast, a tonal analysis readily accounts for the phonetic and distributional facts.
Turbine tent measurements of marine hydrocarbon seeps on subhourly timescales
Authors: Leifer Ira , Boles Jim
Published: January 2005

Three turbine seep‐tents simultaneously measured marine seep gas fluxes with high time resolution (0.2 s) at multiple locations. Tents were inverted polyvinyl cones, 2‐m diameter, 1‐m tall, and weighted on their lower skirt edges. Rising gas bubbles induce vertical fluid motions, which were measured by laboratory‐calibrated turbines in chimneys on top of the tents. Initial deployment was at an active seep area in the Coal Oil Point seep field, in the Santa Barbara Channel, California. The three tents simultaneously collected data for continuous time periods of 2 hours in both the morning and afternoon. Seabed temperature and pressure were acquired every 3 s over the same time periods as the flux measurements from a conductivity temperature depth, CTD, mounted on one tent. Results strongly suggest that oceanic swell had a significant forcing effect on the flux at a subhourly timescale. There was an inverse relationship between effect of swell height on the flux and flux. Swells from 1 to 4 m height and periodicities of 7 and 12 s caused variations of ∼1% to 4% from the average flux. Proposed mechanisms to explain the observations are diffusion with surrounding sediments, termed gas charging, swell induced changes in fracture size, termed fracture forcing, and swell induced vent activation/deactivation, termed pore activation. On the basis of the seep frequency response, we propose pore activation was dominant.
Ecosystem dynamics and export production in the central and eastern equatorial Pacific: A modeling study of impact of ENSO
Authors: Wang Xiujun , Christian James R. , Murtugudde Ragu , Busalacchi Antonio J.
Published: January 2005

Biogeochemical responses to physical changes associated with the El Niño/Southern Oscillation (ENSO) phenomenon are studied for the period of 1990–2001 using a physical‐biogeochemical model. During warm ENSO, the ferricline deepens in the central and eastern equatorial Pacific, resulting in low biomass and low export production. Zooplankton and large phytoplankton are more depressed than small phytoplankton in particular during the 1997–98 El Niño. The recovery from the warm ENSO alleviated iron stress, resulting in an increase of phytoplankton growth. In addition to extra iron input, the mid‐1998 blooms are also attributable to extremely low grazing pressure. The rapid turn to a cold ENSO in mid‐1998 may enhance export production by a factor of eight in the Niño3 area. Large phytoplankton are largely responsible for the increase of export production in the central and eastern equatorial Pacific.
Double trouble for typhoon forecasters
Authors: Peng Melinda S. , Reynolds Carolyn A.
Published: January 2005

The sensitivity of tropical cyclone forecast to changes in the initial state is examined using powerful singular vector diagnostics from a global weather forecast model. These techniques reveal the complex impact of both the local and remote environment on the typhoons. We demonstrate how the analyzed position and forecast of one typhoon can have a significant impact on the forecast of a second typhoon, even at distances up to 1861 km. These results highlight the difficulty of tropical cyclone prediction, especially when remote forcing plays a significant role in tropical cyclone motion.
Contributions of a multimoment multispecies approach in modeling planetary atmospheres: Example of Mars
Authors: Boqueho V. , Blelly P.‐L.
Published: January 2005

Classic approaches in modeling planetary atmospheres, which are based on kinetic transport coefficients, have an upper limitation in altitude due to the transition from collisional to noncollisional regions; consequently, models developed until now have been constrained under the exobase. Furthermore, such models require hypotheses for diffusion coefficients, thermal conductivity, and viscosity in the case where several major species coexist in the medium. In order to solve the whole atmosphere from the ground to the heart of the exosphere, we have developed a new one‐dimensional model based on a collisional approach. This was applied to Mars, using a 13‐moment approximation in order to obtain profiles of the concentrations, velocities, temperatures, heat fluxes, and stress tensors versus altitude for each of the main species (CO2, N2, O2, CO, O, and H). The aim was to validate our mathematical approach and study the dominant physical processes versus altitude. The relevance of the approximations used in classic models was evaluated, and new phenomena that appear above the exobase are presented, all of which have important consequences on concentration, velocity, and temperature profiles. Finally, some modifications are proposed to classic approaches in order to incorporate such mechanisms, and perspectives of the model are presented concerning the interactions between the upper atmosphere and the space environment.
Interplanetary consequences caused by the extremely intense solar activity during October–November 2003
Authors: Tokumaru Munetoshi , Kojima Masayoshi , Fujiki Ken'ichi , Yamashita Masahiro , Baba Daisuke
Published: January 2005

We report interplanetary scintillation (IPS) measurements made by the 327 MHz four‐station system of the Solar‐Terrestrial Environment Laboratory of Nagoya University, during 21 October to 8 November 2003. In this period, solar activity increased greatly owing to the appearance of huge eruptive sunspots on the solar disk. Interplanetary (IP) disturbance events traveling from the Sun beyond the Earth's orbit have been detected clearly from our IPS observations in association with most of the major eruptive events that occurred on the Sun during that period. A possible link between solar/IPS events and near‐Earth (IP shock) events in that same period was investigated in this study. As a result, an IP counterpart was identified by our IPS observations for all of the shock events which occurred during the period, and the link to solar events was established unambiguously for the majority of shock events on the basis of the identification of their IP counterparts. Among the IP disturbance events, the most prominent one occurred between 28 and 29 October 2003, and it is considered as an IP counterpart to the 28 October X17 flare event. Our IPS data revealed a complex feature of this IP disturbance and demonstrated that the global distribution of the solar wind density turbulence settled into a rather quiescent condition after the X17 event except between 2 and 4 November 2003, despite the occurrence of marked solar activities. This is in clear contrast to the fact that enhancements of the turbulence level had taken place frequently before the event. The lack of marked g‐value enhancements for those events is considered partly due to the intrinsic effect related to a change in the global distribution of the solar wind turbulence and partly due to artificial effects inherent in our IPS observations. The radial expansion of the IP disturbance was tracked successfully by consecutive IPS observations during the period between 2 and 4 November in association with the 2 November X8.3 flare event. The movement of this IP disturbance inferred from IPS data was found to be generally consistent with the average transit speed of the IP shock associated with the X8.3 event, although some deceleration of the IP disturbance may have taken place.
Low‐density anomalies and sub‐Alfvénic solar wind
Authors: Usmanov A. V. , Goldstein M. L. , Ogilvie K. W. , Farrell W. M. , Lawrence G. R.
Published: January 2005

During 10–12 May 1999, the solar wind density dropped to an anomalously low value of ∼0.1 cm−3. The density depletion occurred in the midst of relatively slow wind flow, in between faster flows, and was apparently associated with neither a coronal mass ejection nor a fast corotating stream. While the magnetic field intensity did not show any notable variation across the density depletion, plasma analyzers on the ACE and Wind spacecraft revealed an abnormally strong nonradial flow component with an azimuthal speed that peaked at ∼100 km s−1. Usmanov et al. [2000b] suggested that the density anomaly was, in fact, a rarefaction at the trailing edge of relatively fast flow that formed as a result of suppression of coronal outflow from a region that earlier provided fast wind flow. The suppression in turn may have resulted from a rapid restructuring of solar magnetic fields during the polar field reversal. Here we show results from a two‐dimensional time‐dependent MHD simulation applied to the helioequatorial plane. The initially longitude‐independent Parker solar wind and Archimedean spiral magnetic field are disturbed by a low‐velocity/high‐density jump on an inner computational boundary at 20 R⊙. We follow the development and propagation of the rarefaction to Earth orbit and compare pseudo‐time series with near‐Earth spacecraft measurements. We show that a strong rarefaction can develop behind the fast flow and that simulation results and spacecraft observations are generally in agreement. The simulated radial magnetic field shows a relatively small variation across the density anomaly compared with that of the density. The stream interaction generates strong azimuthal velocities in the slow flow region, as observed. The simulation shows a sub‐Alfvénic flow region embedded within the low‐density region that does not extend all the way back to the Sun but which has become disconnected as the depletion propagates to Earth orbit. We discuss also the correlation between low‐density and sub‐Alfvénic events in the solar wind as inferred from spacecraft observations using the OMNI 2 data set from 1963 to 2003.
Solar EUV Experiment (SEE): Mission overview and first results
Authors: Woods Thomas N. , Eparvier Francis G. , Bailey Scott M. , Chamberlin Phillip C. , Lean Judith , Rottman Gary J. , Solomon Stanley C. , Tobiska W. Kent , Woodraska Donald L.
Published: January 2005

The Solar EUV Experiment (SEE) is one of four scientific instruments on the NASA Thermosphere Ionosphere Mesosphere Energetics Dynamics (TIMED) spacecraft, which has been simultaneously observing the Sun and Earth's upper atmosphere since January 2002. The SEE instrument measures the irradiance of the highly variable, solar extreme ultraviolet (EUV) radiation, one of the major energy sources for the upper atmosphere. The primary SEE data product is the solar spectral irradiances from 0.1 to 194 nm in 1 nm intervals that are fundamental for the TIMED mission's investigation of the energetics in the tenuous, but highly variable, layers of the Earth's atmosphere above 60 km. The TIMED mission began normal operations on 22 January 2002, a time when the Sun displayed maximum levels of activity for solar cycle 23, and has provided daily measurements as solar activity has declined to moderate levels. Solar irradiance variability observed by SEE during the 2 years of the TIMED prime mission includes a variety of moderate and large flares over periods of seconds to hours and dozens of solar rotational cycles over a typical period of 27 days. The SEE flare measurements provide important, new results because of the simultaneous spectral coverage from 0.1 to 194 nm, albeit limited temporal coverage due to its 3% duty cycle. In addition, the SEE measurements reveal important, new results concerning phase shifts of 2–7 days in the intermediate‐term variations between different UV wavelengths that appear to be related to their different center‐to‐limb variations. The new solar EUV irradiance time series from SEE are also important in filling the “EUV Hole,” which is the gap in irradiance measurements in the EUV spectrum since the 1980s. The solar irradiances measured by SEE (Version 7, released July 2004) are compared with other measurements and predictions from models of the solar EUV irradiance. While the measurement comparisons show reasonable agreement, there are significant differences between SEE and some of the models in the EUV range. The data processing algorithms and calibrations are also discussed.
Do geochemical estimates of sediment focusing pass the sediment test in the equatorial Pacific?
Authors: Lyle Mitchell , Mitchell Neil , Pisias Nicklas , Mix Alan , Martinez Jose Ignacio , Paytan Adina
Published: January 2005

The paleoceanographic recording fidelity of pelagic sediments is limited by chemical diagenesis and physical mixing (bioturbation and horizontal sediment transport). Diagenesis and bioturbation are relatively well‐studied, but the effects of physical sedimentation have been largely ignored. Modeling U series isotopes (e.g., 230Th) can potentially quantify horizontal sediment movement, but model horizontal sediment focusing often equals or exceeds the vertical particle rain. We find no evidence of this level of sediment focusing in the equatorial Pacific from geophysical data or sediment core comparisons. The overestimate of sediment focusing by 230Th is probably caused by poor model assumptions: that sediment does not fractionate (does not sort according to size during transport) and that 230Th cannot leak from slowly accumulating sediments. Both assumptions are weak. U series methods do hold promise to quantify sediment focusing if properly calibrated. With calibration the trade‐offs between seeking high sedimentation rates for better time resolution and the blurring by horizontal sediment focusing can be better assessed.
Studies using isolated uterine and other preparations show bimatoprost and prostanoid FP agonists have different activity profiles
Authors: Chen June , Senior Judith , Marshall Kay , Abbas Farhat , Dinh Helen , Dinh Tim , Wheeler Larry , Woodward David
Published: January 2005

The pharmacology of bimatoprost, a synthetic prostaglandin‐amide, was examined in prostaglandin F2α (PGF2α)‐sensitive preparations. Bimatoprost potently contracted the rabbit isolated uterus (pEC50=7.92±0.16). In contrast, bimatoprost exhibited weak excitatory activity in human myometrium from pregnant and nonpregnant donors, mouse uterus, rat uterus, and endothelium‐intact rabbit jugular veins, and did not stimulate DNA synthesis in mouse fibroblasts.

The possibility that the effects of bimatoprost may reflect partial agonism at prostanoid FP receptors was examined and the contractile effects of full agonists, 17‐phenyl PGF2α (FP) and U‐46619 (TP, a control), were determined in the absence and presence of 1 μM bimatoprost on the mouse uterus. Analyses of the agonist–agonist functional studies showed no antagonism, indicating that bimatoprost is not a partial agonist.

Bioassay metabolism studies of bimatoprost and latanoprost (FP receptor agonist prodrug) in the rabbit uterus were conducted using recipient mouse uterus. Results indicated that the potent responses to bimatoprost in the rabbit uterus are produced by the intact molecule and not by its putative free acid metabolite, 17‐phenyl PGF2α. Some hydrolysis of latanoprost to latanoprost free acid appears to have occurred in the rabbit uterus, according to biological detection.

The pharmacology of bimatoprost could not be explained by its interaction with known prostanoid FP receptors and was independent of species‐, tissue‐, or preparation‐related factors. The potent contractile effects of bimatoprost in the rabbit uterus provide further pharmacological evidence for the presence of a novel receptor population that preferentially recognises bimatoprost.

British Journal of Pharmacology (2005) 144, 493–501. doi:10.1038/sj.bjp.0706044
Kir6.2‐dependent high‐affinity repaglinide binding to β‐cell KATP channels
Authors: Hansen Ann Maria K , Hansen John Bondo , Carr Richard D , Ashcroft Frances M , Wahl Philip
Published: January 2005

The β‐cell KATP channel is composed of two types of subunit – the inward rectifier K+ channel (Kir6.2) which forms the channel pore, and the sulphonylurea receptor (SUR1), which serves as a regulatory subunit. The N‐terminus of Kir6.2 is involved in transduction of sulphonylurea binding into channel closure, and deletion of the N‐terminus (Kir6.2ΔN14) results in functional uncoupling of the two subunits. In this study, we investigate the interaction of the hypoglycaemic agents repaglinide and glibenclamide with SUR1 and the effect of Kir6.2 on this interaction. We further explore how the binding properties of repaglinide and glibenclamide are affected by functional uncoupling of SUR1 and Kir6.2 in Kir6.2ΔN14/SUR1 channels. All binding experiments are performed on membranes in ATP‐free buffer at 37°C.

Repaglinide was found to bind with low affinity (KD=59±16 nM) to SUR1 alone, but with high affinity (increased ∼150‐fold) when SUR1 was co‐expressed with Kir6.2 (KD=0.42±0.03 nM). Glibenclamide, tolbutamide and nateglinide all bound with marginally lower affinity to SUR1 than to Kir6.2/SUR1.

Repaglinide bound with low affinity (KD=51±23 nM) to SUR1 co‐expressed with Kir6.2ΔN14. In contrast, the affinity for glibenclamide, tolbutamide and nateglinide was only mildly changed as compared to wild‐type channels.

In whole‐cell patch‐clamp experiments inhibition of Kir6.2ΔN14/SUR1 currents by both repaglinide and nateglinde is abolished.

The results suggest that Kir6.2 causes a conformational change in SUR1 required for high‐affinity repaglinide binding, or that the high‐affinity repaglinide‐binding site includes contributions from both SUR1 and Kir6.2. Glibenclamide, tolbutamide and nateglinide binding appear to involve only SUR1.

British Journal of Pharmacology (2005) 144, 551–557. doi:10.1038/sj.bjp.0706082
Responses of the sustained inward current to autonomic agonists in guinea‐pig sino‐atrial node pacemaker cells
Authors: Toyoda Futoshi , Ding Wei‐Guang , Matsuura Hiroshi
Published: January 2005

The present study was undertaken to examine the responses of the sustained inward current (Ist) to β‐adrenergic and muscarinic agonists in guinea‐pig sino‐atrial (SA) node cells using the whole‐cell patch‐clamp technique. Ist was detected as the nicardipine (1 μM)‐sensitive inward current at potentials between ∼−80 and +20 mV in the presence of low concentration (0.1 mM) of extracellular Ca2+, where the L‐type Ca2+ current (ICa,L) was practically abolished.

β‐adrenergic agonist isoprenaline (ISO) in nanomolar concentrations not only increased the amplitude of Ist but also shifted the membrane potential producing the peak amplitude (Vpeak) to a negative direction by ∼15 mV without appreciably affecting potential range for the current activation. The stimulatory effect of ISO was concentration‐dependent with an EC50 of 2.26 nM and the maximal effect (96.4±22.9% increase, n=6) was obtained at 100 nM ISO, when evaluated by the responses at −50 mV.

Bath application of acetylcholine (ACh) significantly inhibited Ist, which had been maximally augmented by 100 nM ISO; this inhibitory effect of ACh was concentration‐dependent with an IC50 of 133.9 nM. High concentration (1000 nM) of ACh depressed basal Ist by 10.5±2.0% (n=3).

In action potential clamp experiments, Ist was also detected under control conditions and was markedly potentiated by exposure to ISO.

These results strongly suggest that Ist not only contributes to the spontaneous action potentials of mammalian SA node cells but also plays a substantial role in mediating autonomic regulation of SA node pacemaker activity.

British Journal of Pharmacology (2005) 144, 660–668. doi:10.1038/sj.bjp.0706101
Characterisation of opioid receptors involved in modulating circular and longitudinal muscle contraction in the rat ileum
Authors: Gray Andrew C , White Paul J , Coupar Ian M
Published: January 2005

The aim of the present investigation was to characterise the opioid receptor subtypes present in the rat ileum using a method that detects drug action on the enteric nerves innervating the circular and longitudinal muscles.

Neurogenic contractions were reversibly inhibited by morphine (circular muscle pEC50, 6.43±0.17, Emax 81.7±5.0%; longitudinal muscle pEC50, 6.65±0.27, Emax 59.7±7.8%), the μ‐opioid receptor‐selective agonist, DAMGO ([D‐Ala2,N‐Me‐Phe4,Gly5‐ol]enkephalin acetate) (circular pEC50, 7.85±0.04, Emax 97.8±3.6%; longitudinal pEC50, 7.35±0.09, Emax 56.0±6.1%), the δ‐selective agonist DADLE ([D‐Ala2,D‐Leu5]enkephalin acetate) (circular pEC50, 7.41±0.17, Emax, 93.3±8.4%; longitudinal pEC50, 6.31±0.07, Emax 66.5±5.2%) and the κ‐selective agonist U 50488H (trans‐(±)‐3,4‐dichloro‐N‐methyl‐N‐[2‐(1‐pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulphonate) (circular pEC50, 5.91±0.41, Emax, 83.5±26.8%; longitudinal pEC50, 5.60±0.08, Emax 74.3±7.2%). Agonist potencies were generally within expected ranges for activity at the subtype for which they are selective, except for U 50488H, which was less potent than expected.

The μ and δ receptor‐selective antagonists, CTAP (H‐D‐Phe‐Cys‐Tyr‐D‐Trp‐Arg‐Thr‐Pen‐Thr‐NH2) and naltrindole, caused progressive, parallel rightward shifts in the DAMGO and DADLE curves, respectively. Analysis indicated conformity to theoretical simple competitive antagonist behaviour. U 50488H effects were insensitive to the κ‐selective antagonist, n‐BNI. A high concentration (1 μM) of naltrexone caused apparent potentiation of U 50488H effects.

CTAP pKB estimates were consistent with previously reported values for μ receptor antagonism (circular 7.84±0.17, longitudinal 7.64±0.35). However, the naltrindole pKB estimates indicated lower antagonist potency than expected (circular 8.22±0.23, longitudinal 8.53±0.35).

It is concluded that μ and possibly atypical δ receptors (but not κ receptors) mediate inhibition of contraction in this model. Nonopioid actions of U 50488H are probably responsible for the inhibitory effects seen with this compound.

British Journal of Pharmacology (2005) 144, 687–694. doi:10.1038/sj.bjp.0706107
Relationship between brain serotonin transporter binding, plasma concentration and behavioural effect of selective serotonin reuptake inhibitors
Authors: Hirano Kazufumi , Kimura Ryohei , Sugimoto Yumi , Yamada Jun , Uchida Shinya , Kato Yasuhiro , Hashimoto Hisakuni , Yamada Shizuo
Published: January 2005

The present study was undertaken to characterise the relationship between in vivo brain serotonin transporter (SERT) binding, plasma concentration and pharmacological effect of selective serotonin reuptake inhibitors (SSRIs) in mice. Oral administration of fluvoxamine, fluoxetine, paroxetine and sertraline at pharmacologically relevant doses exerted dose‐ and time‐dependent binding activity of brain SERT as revealed by significant increases in KD for specific [3H]paroxetine binding, and the in vivo SERT‐binding potency was in the order of paroxetine≫fluoxetine, sertraline>fluvoxamine.

The time courses of brain SERT binding by SSRIs in mice were mostly in parallel to those of their plasma concentrations. Also, norfluoxetine (active metabolite) has been suggested to contribute largely to the long‐lasting binding activity of brain SERT after the fluoxetine administration.

Oral administration of each SSRI suppressed significantly the marble‐burying behaviour with no change in locomotor activity in mice, and the extent and time course of suppression agreed well with those of brain SERT binding. Thus, the pharmacological potencies of SSRIs in the attenuation of marble‐burying behaviour correlated significantly with their brain SERT binding activities.

In conclusion, the present study has provided the first in vivo evidences to support that fluvoxamine, fluoxetine, paroxetine and sertraline orally administered bind to the pharmacologically relevant brain SERT in mice and that their SERT‐binding characteristics is closely associated with the pharmacokinetics and inhibition of marble‐burying behaviour.

British Journal of Pharmacology (2005) 144, 695–702. doi:10.1038/sj.bjp.0706108
Role of descending noradrenergic system and spinal α2‐adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse
Authors: Tanabe Mitsuo , Takasu Keiko , Kasuya Noriyo , Shimizu Shinobu , Honda Motoko , Ono Hideki
Published: January 2005

To gain further insight into the mechanisms underlying the antihyperalgesic and antiallodynic actions of gabapentin, a chronic pain model was prepared by partially ligating the sciatic nerve in mice. The mice then received systemic or local injections of gabapentin combined with either central noradrenaline (NA) depletion by 6‐hydroxydopamine (6‐OHDA) or α‐adrenergic receptor blockade.

Intraperitoneally (i.p.) administered gabapentin produced antihyperalgesic and antiallodynic effects that were manifested by elevation of the withdrawal threshold to a thermal (plantar test) or mechanical (von Frey test) stimulus, respectively.

Similar effects were obtained in both the plantar and von Frey tests when gabapentin was injected intracerebroventricularly (i.c.v.) or intrathecally (i.t.), suggesting that it acts at both supraspinal and spinal loci. This novel supraspinal analgesic action of gabapentin was only obtained in ligated neuropathic mice, and gabapentin (i.p. and i.c.v.) did not affect acute thermal and mechanical nociception.

In mice in which central NA levels were depleted by 6‐OHDA, the antihyperalgesic and antiallodynic effects of i.p. and i.c.v. gabapentin were strongly suppressed.

The antihyperalgesic and antiallodynic effects of systemic gabapentin were reduced by both systemic and i.t. administration of yohimbine, an α2‐adrenergic receptor antagonist. By contrast, prazosin (i.p. or i.t.), an α1‐adrenergic receptor antagonist, did not alter the effects of gabapentin.

It was concluded that the antihyperalgesic and antiallodynic effects of gabapentin are mediated substantially by the descending noradrenergic system, resulting in the activation of spinal α2‐adrenergic receptors.

British Journal of Pharmacology (2005) 144, 703–714. doi:10.1038/sj.bjp.0706109
Effects of diltiazem and nifedipine on transient outward and ultra‐rapid delayed rectifier potassium currents in human atrial myocytes
Authors: Gao Zhan , Sun Haiying , Chiu Shui‐Wah , Lau Chu‐Pak , Li Gui‐Rong
Published: January 2005

It is unknown whether the widely used L‐type Ca2+ channel antagonists diltiazem and nifedipine would block the repolarization K+ currents, transient outward current (Ito1) and ultra‐rapid delayed rectifier K+ current (IKur), in human atrium. The present study was to determine the effects of diltiazem and nifedipine on Ito1 and IKur in human atrial myocytes with whole‐cell patch‐clamp technique.

It was found that diltiazem substantially inhibited Ito1 in a concentration‐dependent manner, with an IC50 of 29.2±2.4 μM, and nifedipine showed a similar effect (IC50=26.8±2.1 μM). The two drugs had no effect on voltage‐dependent kinetics of the current; however, they accelerated Ito1 inactivation significantly, suggesting an open channel block.

In addition, diltiazem and nifedipine suppressed IKur in a concentration‐dependent manner (at +50 mV, IC50=11.2±0.9 and 8.2±0.8 μM, respectively). These results indicate that the Ca2+ channel blockers diltiazem and nifedipine substantially inhibit Ito1 and IKur in human atrial myocytes.

British Journal of Pharmacology (2005) 144, 595–604. doi:10.1038/sj.bjp.0706113
Capsaicin exhibits neuroprotective effects in a model of transient global cerebral ischemia in Mongolian gerbils
Authors: Pegorini Simona , Braida Daniela , Verzoni Chiara , Guerini‐Rocco Chiara , Consalez Gian Giacomo , Croci Laura , Sala Mariaelvina
Published: January 2005

Capsaicin, the irritant principle of hot peppers, is a vanilloid agonist known to activate the transient receptor potential channel vanilloid subfamily member 1 (VR1), recently reported to be involved in neurodegeneration. The present study investigated the role of VR1 in a model of global cerebral ischemia in gerbils.

Over the dose range tested, capsaicin (0.01, 0.025, 0.05, 0.2 and 0.6 mg kg−1), given 5 min after recirculation, dose‐dependently antagonized the ischemia‐induced electroencephalographic total spectral power decrease and restored relative frequency band distribution evaluated 7 days after ischemia.

Capsaicin, at all tested doses, fully prevented ischemia‐induced hyperlocomotion evaluated 1 day after ischemia.

Capsaicin dose‐dependently antagonized ischemia‐induced memory impairment evaluated in a passive avoidance task, 3 days after ischemia.

Capsaicin showed a dose‐dependent hypothermic effect evaluated for 2 h after recirculation.

At 7 days after ischemia, a progressive survival of pyramidal cells in the CA1 subfield in capsaicin‐treated gerbils, with a maximum of 80%, at a dose of 0.2 mg kg−1, was obtained.

The selective VR1 antagonist, capsazepine (0.01 mg kg−1), reversed capsaicin‐induced protective effects, in a competitive manner.

These results suggest that the neuroprotective effect of capsaicin may be attributable, at least in part, to VR1 desensitization and provide a valuable target for development of interventional pharmacological strategies.

British Journal of Pharmacology (2005) 144, 727–735. doi:10.1038/sj.bjp.0706115
Neurobarrier Coupling in the Brain: A Partner of Neurovascular and Neurometabolic Coupling?
Authors: Leybaert Luc
Published: January 2005

Neurovascular and neurometabolic coupling help the brain to maintain an appropriate energy flow to the neural tissue under conditions of increased neuronal activity. Both coupling phenomena provide us, in addition, with two macroscopically measurable parameters, blood flow and intermediate metabolite fluxes, that are used to dynamically image the functioning brain. The main energy substrate for the brain is glucose, which is metabolized by glycolysis and oxidative breakdown in both astrocytes and neurons. Neuronal activation triggers increased glucose consumption and glucose demand, with new glucose being brought in by stimulated blood flow and glucose transport over the blood-brain barrier. Glucose is shuttled over the barrier by the GLUT-1 transporter, which, like all transporter proteins, has a ceiling above which no further stimulation of the transport is possible. Blood-brain barrier glucose transport is generally accepted as a nonrate-limiting step but to prevent it from becoming rate-limiting under conditions of neuronal activation, it might be necessary for the transport parameters to be adapted to the increased glucose demand. It is proposed that the blood-brain barrier glucose transport parameters are dynamically adapted to the increased glucose needs of the neural tissue after activation according to a neurobarrier coupling scheme. This review presents neurobarrier coupling within the current knowledge on neurovascular and neurometabolic coupling, and considers arguments and evidence in support of this hypothesis.
Neuronal Activation of NF-κB Contributes to Cell Death in Cerebral Ischemia
Authors: Zhang Wen , Potrovita Ioana , Tarabin Victoria , Herrmann Oliver , Beer Verena , Weih Falk , Schneider Armin , Schwaninger Markus
Published: January 2005

The transcription factor NF-κB is a key regulator of inflammation and cell survival. NF-κB is activated by cerebral ischemia in neurons and glia, but its function is controversial. To inhibit NF-κB selectively in neurons and glial cells, we have generated transgenic mice that express the IκBα superrepressor (IκBα mutated at serine-32 and serine-36, IκBα-SR) under transcriptional control of the neuron-specific enolase (NSE) and the glial fibrillary acidic protein (GFAP) promoter, respectively. In primary cortical neurons of NSE-IκBα-SR mice, NF-κB activity was partially inhibited. To assess NF-κB activity in vivo after permanent middle cerebral artery occlusion (MCAO), we measured the expression of NF-κB target genes by real-time polymerase chain reaction (PCR). The induction of c-myc and transforming growth factor-β2 by cerebral ischemia was inhibited by neuronal expression of IκBα-SR, whereas induction of GFAP by MCAO was reduced by astrocytic expression of IκBα-SR. Neuronal, but not astrocytic, expression of the NF-κB inhibitor reduced both infarct size and cell death 48 hours after permanent MCAO. In summary, the data show that NF-κB is activated in neurons and astrocytes during cerebral ischemia and that NF-κB activation in neurons contributes to the ischemic damage.
A Quantitative Study of Microglial—Macrophage Synthesis of Tumor Necrosis Factor during Acute and Late Focal Cerebral Ischemia in Mice
Authors: Lambertsen Kate Lykke , Meldgaard Michael , Ladeby Rune , Finsen Bente
Published: January 2005

Understanding the role of tumor necrosis factor (TNF) in the life-death balance of ischemically injured neurons demands insight into the cellular synthesis of TNF, especially in the acute phase after induction of ischemia. Here, using approximated stereological methods and quantitative reverse transcription (RT) real-time polymerase chain reaction (PCR) analysis, the cellular synthesis of TNF from 30 mins to 10 days after induction of focal cerebral ischemia in mice was investigated. Reverse transcription real-time PCR analysis showed that TNF mRNA increased 2- to 3-fold within 1 hour after induction of ischemia. A significant 8-fold increase was observed at 4 hours when faintly labelled TNF mRNA-expressing and TNF immunoreactive microglial-like cells were easily identifiable in the peri-infarct and infarct. By 6 hours, TNF synthesizing cells were identified as Mac-1 immunopositive, glial fibrillary acidic protein immunonegative microglia-macrophages. The level of TNF mRNA and the numbers of TNF mRNA-expressing microglia-macrophages peaked at 12 hours, and the number of TNF immunoreactive cells at 24 hours. Neuronal TNF mRNA and TNF protein levels remained at constant, very low, levels. The data suggest that the pathophysiologically important TNF, produced in the acute phase from mins to 6 hours after an ischemic attack in mice, is synthesized by microglia-macrophages.
Reflex-Mediated Reduction in Human Cerebral Blood Volume
Authors: Wilson Timothy D , Shoemaker J Kevin , Kozak R , Lee T-Y , Gelb Adrian W
Published: January 2005

Adrenergic nerves innervate the human cerebrovasculature, yet the functional role of neurogenic influences on cerebral hemodynamics remains speculative. In the current study, regional cerebrovascular responses to sympathoexcitatory reflexes were evaluated. In eight volunteers, contrast-enhanced computed tomography was performed at baseline, –40 mmHg lower body negative pressure (LBNP), and a cold pressor test (CPT). Cerebral blood volume (CBV), mean transit time (MTT), and cerebral blood flow (CBF) were evaluated in cortical gray matter (GM), white matter (WM), and basal ganglia/thalamus (BGT) regions. Lower body negative pressure resulted in tachycardia and decreased central venous pressure while mean arterial pressure was maintained. Cold pressor test resulted in increased mean arterial pressure concomitant with tachycardia but no change in central venous pressure. Neither reflex altered end-tidal carbon dioxide. Cerebral blood volume was reduced in GM during both LBNP and CPT ( P<0.05) but was unchanged in WM and BGT. Mean transit time was reduced in WM and GM during CPT ( P<0.05). Cerebral blood flow was only modestly affected with either reflex ( P<0.07). The combined reductions in GM CBV (˜ –25%) and MTT, both with and without any change in central venous pressure, with small CBF changes (˜ –11%), suggest that active venoconstriction contributed to the volume changes. These data demonstrate that CBV is reduced during engagement of sympathoexcitatory reflexes and that these cerebrovascular changes are heterogeneously distributed.
Atorvastatin Induction of VEGF and BDNF Promotes Brain Plasticity after Stroke in Mice
Authors: Chen Jieli , Zhang Chunling , Jiang Hao , Li Yi , Zhang Lijie , Robin Adam , Katakowski Mark , Lu Mei , Chopp Michael
Published: January 2005

Molecular mechanisms underlying the role of statins in the induction of brain plasticity and subsequent improvement of neurologic outcome after treatment of stroke have not been adequately investigated. Here, we use both in vivo and in vitro studies to investigate the potential roles of two prominent factors, vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF), in mediating brain plasticity after treatment of stroke with atorvastatin. Treatment of stroke in adult mice with atorvastatin daily for 14 days, starting at 24 hours after MCAO, shows significant improvement in functional recovery compared with control animals. Atorvastatin increases VEGF, VEGFR2 and BDNF expression in the ischemic border. Numbers of migrating neurons, developmental neurons and synaptophysin-positive cells as well as indices of angiogenesis were significantly increased in the atorvastatin treatment group, compared with controls. In addition, atorvastatin significantly increased brain subventricular zone (SVZ) explant cell migration in vitro. Anti-BDNF antibody significantly inhibited atorvastatin-induced SVZ explant cell migration, indicating a prominent role for BDNF in progenitor cell migration. Mouse brain endothelial cell culture expression of BDNF and VEGFR2 was significantly increased in atorvastatin-treated cells compared with control cells. Inhibition of VEGFR2 significantly decreased expression of BDNF in brain endothelial cells. These data indicate that atorvastatin promotes angiogenesis, brain plasticity and enhances functional recovery after stroke. In addition, VEGF, VEGFR2 and BDNF likely contribute to these restorative processes.
Detecting synchronizations in an asymmetric vocal fold model from time series data
Authors: Tokuda Isao , Herzel Hanspeter
Published: January 2005

A nonlinear modeling approach is presented for the reconstruction of the synchronization structure in an asymmetric two-mass model from time series data. The asymmetric two-mass model describes a variety of normal and pathological human voices associated with synchronous and desynchronous oscillations of the two asymmetric vocal folds. Our technique recovers the synchronization diagram, which yields the regimes of synchronization as well as desynchronization, which are dependent upon the asymmetry parameter and the subglottal pressure. This allows the prediction of the regime of pathological phonation associated with desynchronization of the vocal folds from a few sets of recorded time series. It is shown that the modeling is quite effective when the time series data are chaotic and if they are taken from a regime of desynchronization. We discuss the applicability of the present approach as a diagnostic tool for voice pathologies.
Numerical simulations of high density ratio lock-exchange flows
Authors: Étienne Jocelyn , Hopfinger Emil J. , Saramito Pierre
Published: January 2005

In this paper direct numerical simulations of exchange flows of large density ratios are presented and are compared with experiments by Gröbelbauer et al. [J. Fluid Mech. 250, 669 (1993)]. These simulations, which make use of a dynamic mesh adaptation technique, cover the whole density ratio range of the experiments and very good agreement with the experimental front velocities and the Froude number variations is obtained. Moreover, in order to establish more definitely the Froude number dependency on density ratio, the simulations were carried up to ratios of 100 compared with 21.6 accessible in experiments. An empirical law for the dense front Froude number as a function of the density parameter is proposed. The mathematical difficulty of the problem is discussed. This difficulty arises because, when the density ratio is large, the existence of a solution is dependent on a compatibility condition between the diffusion and viscous terms model. Moreover, a specific numerical technique is required to treat the finite, nonuniform divergence of the mass-averaged velocity field described by the continuity equation.
Instability of isolated compressible entropy-stratified vortices
Authors: Men’shov Igor , Nakamura Yoshiaki
Published: January 2005

The normal mode linear analysis is applied to investigate the stability of a circular isolated compressible vortex with the emphasis on studying the effect of entropy stratification of the basic flow on stability properties. We study a family of vortices that have zero total circulation, with the swirl velocity being presented by a Taylor-type distribution in the radial direction. The stratification of entropy is modeled by a Gaussian two-parametric profile whose parameters control the maximal deviation from the homentropic distribution and the extent of the entropic zone. Results presented concern the effect of these parameters and the vortex intensity on instability characteristics. In particular, in the case of homentropic flow, vortices considered are found to be stable only for sufficiently high intensities and cease to be stable as the intensity weakens. As an example of the situation where unstable normal modes can be excited, the scattering of sound waves by the vortex flow is considered. By simulating this process numerically, we show that the scattered field becomes unstable in the course of time and acquires a typical periodical pattern in polar angle. The characteristics of this instability (viz., the growth rate and the azimuthal phase frequency) coincide with those of the linear analysis very closely. This fact shows conclusively that the instability is caused by the induction of unstable normal modes in the vortex by means of sound irradiation.
Droplet distributions at the liquid core of a turbulent spray
Authors: Yoon Sam S.
Published: January 2005

Initial droplet distributions at the liquid core are examined for various Weber number and pulsing conditions. While experimental investigation in the liquid core region is nearly impossible due to difficulty in the optical access to the region, the distribution at the region is investigated computationally, and typical droplet distributions are identified. It is found that the Nukiyama–Tanasawa and log-normal distributions can best describe the droplet size and velocity distributions, respectively. By comparing computational results obtained at the liquid core (0<x<8mm) and experimental data collected at x=48mm, it is suspected that the droplet gradation occurs immediately after droplets are separated from the liquid core. Thus, the distribution shape changes rapidly in both axial and radial directions. Such droplet–gradation behavior is numerically confirmed when the Nukiyama–Tanasawa droplet size distribution is used as an initial condition for the stochastic separated flow model. When the jet velocity is increased, the width of the droplet-size distribution becomes narrower, while the droplet velocity distribution becomes broader. Possible physical mechanism for that behavior is discussed in detail. Pulsing injection prominently influences the external spray shape near the nozzle exit. However, the overall droplet size and velocity distributions of the liquid core due to the pulsing injection are relatively insignificant for a turbulent spray in the atomization regime.