bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substance P modulates localized calcium transients and membrane current responses in murine colonic myocytes
Authors: Bayguinov Orline , Hagen Brian , Sanders Kenton M 
Published: April 2003

Neurokinins contribute to the neural regulation of gastrointestinal (GI) smooth muscles. We studied responses of murine colonic smooth muscle cells to substance P (SP) and NK1 and NK2 agonists using confocal microscopy and the patch clamp technique.
Colonic myocytes generated localized Ca2+ transients that were coupled to spontaneous transient outward currents (STOCs). SP (10−10 M) increased Ca2+ transients and STOCs. Higher concentrations of SP (10−6 M) increased basal Ca2+ and inhibited Ca2+ transients and STOCs.
Effects of SP were due to increased Ca2+ entry via L‐type Ca2+ channels, and were mediated by protein kinase C (PKC). Nifedipine (10−6 M) and the PKC inhibitor, GF 109203X (10−6 M) reduced L‐type Ca2+ current and blocked the effects of SP.
SP responses depended upon parallel stimulation of NK1 and NK2 receptors. NK1 agonist ([Sar9,Met(O2)11]‐substance P; SSP) and NK2 agonists (neurokinin A (NKA) or GR‐64349) did not mimic the effects of SP alone, but NK1 and NK2 agonists were effective when added in combination (10−10–10−6 M). Consistent with this, either an NK1‐specific antagonist (GR‐82334; 10−7 M) or an NK2‐specific antagonist (MEN 10,627; 10−7 M) blocked responses to SP (10−6 M).
Ryanodine (10−5 M) blocked the increase in Ca2+ transients and STOCs in response to SP (10−10 M).
Our findings show that low concentrations of SP, via PKC‐dependent enhancement of L‐type Ca2+ current and recruitment of ryanodine receptors, stimulate Ca2+ transients. At higher concentrations of SP (10−6 M), basal Ca2+ increases and spontaneous Ca2+ transients and STOCs are inhibited.

British Journal of Pharmacology (2003) 138, 1233–1243. doi:10.1038/sj.bjp.0705139
Stimulation of P2 purinergic receptors induces the release of eosinophil cationic protein and interleukin‐8 from human eosinophils
Authors: Idzko Marco , Panther Elisabeth , Bremer Hinrich C , Sorichter Stephan , Luttmann Werner , Virchow Christian J , Di Virgilio Francesco , Herouy Yared , Norgauer Johannes , Ferrari Davide 
Published: April 2003

Extracellular nucleotides are the focus of increasing attention for their role as extracellular mediators since they are released into the extracellular environment in a regulated manner and/or as a consequence of cell damage.
Here, we show that human eosinophils stimulated with different nucleotides release eosinophil cationic protein (ECP) and the chemokine interleukin 8 (IL‐8), and that release of these two proteins has a different nucleotide requirement.
Release of ECP was triggered in a dose‐dependent manner by ATP, UTP and UDP, but not by 2′‐&3′‐o‐(4‐benzoyl‐benzoyl)adenosine 5′‐triphosphate (BzATP), ADP and α,β‐methylene adenosine 5′ triphosphate (α,β‐meATP). Release of IL‐8 was triggered by UDP, ATP, α,β‐meATP and BzATP, but not by UTP or ADP. Pretreatment with pertussis toxin abrogated nucleotide‐stimulated ECP but not IL‐8 release.
Release of IL‐8 stimulated by BzATP was fully blocked by the P2X7 blocker KN‐62, while release triggered by ATP was only partially inhibited. IL‐8 secretion due to UDP was fully insensitive to KN‐62 inhibition.
Priming of eosinophils with GM‐CSF increased IL‐8 secretion irrespectively of the nucleotide used as a stimulant.
It is concluded that extracellular nucleotides trigger secretion of ECP by stimulating a receptor of the P2Y subfamily (possibly P2Y2), while, on the contrary, nucleotide‐stimulated secretion of IL‐8 can be due to activation of both P2Y (P2Y6) and P2X (P2X1 and P2X7) receptors.

British Journal of Pharmacology (2003) 138, 1244–1250. doi:10.1038/sj.bjp.0705145
Effect of tumour necrosis factor‐α and interleukin 1β on endothelium‐dependent relaxation in rat mesenteric resistance arteries in vitro
Authors: Wimalasundera R , Fexby S , Regan L , Thom S A McG , Hughes A D 
Published: April 2003

Pre‐eclampsia is associated with elevated proinflammatory cytokine levels and endothelial dysfunction. This study examined the effect of two cytokines, tumour necrosis factor‐α (TNF) and interleukin‐1β (IL‐1) on endothelium‐dependent relaxation in response to acetylcholine (ACH), bradykinin (BK) and histamine (HIS) in rat mesenteric small arteries in vitro.
Rat mesenteric arteries were mounted in an isometric myograph. Tone was induced with phenylephrine (PE) or a depolarizing solution containing 80 mM KCl (K80). Relaxation was measured in response to ACH, BK, HIS and sodium nitroprusside (SNP), an endothelium‐independent relaxant. Inhibition of NO synthase by a combination of Nω‐monomethyl‐L‐arginine (L‐NMMA) and Nω‐nitro‐L‐arginine methyl ester (L‐NAME) significantly inhibited relaxation in response to ACH and BK. Addition of an inhibitor of cyclooxygenase, indomethacin, had no additional effect when added to L‐NMMA and L‐NAME. Inhibition of endothelium‐derived hyperpolarizing factor (EDHF) by K80 partially reduced responses to ACH and BK. Inhibition of HIS‐induced relaxation was more marked with K80. L‐NMMA and L‐NAME largely abolished the remaining relaxation to ACH, BK and HIS in arteries contracted with K80.
Preincubation with TNF for 30 min caused an inhibition of relaxation in response to ACH and BK in arteries contracted with PE. Responses to HIS and SNP were not affected by TNF under these conditions. TNF also inhibited ACH‐induced relaxation in arteries contracted with K80. IL‐1 had no effect on responses to ACH and the combination of TNF and IL‐1 was not more effective than TNF alone.
The inhibitory effect of TNF on ACH‐induced relaxation was abolished by coincubation with superoxide dismutase (SOD) and was not seen if NO synthase was inhibited by L‐NMMA and L‐NAME.
TNF inhibits the NO‐dependent component of endothelium‐dependent relaxation in response to ACH and BK, but does not inhibit the EDHF‐dependent component. This effect may be attributable to the ability of TNF to increase levels of superoxide anions (O2−) and the ability of O2− to inactivate NO. This mechanism could contribute to the endothelial dysfunction seen in situations where TNF is elevated, such as pre‐eclampsia.

British Journal of Pharmacology (2003) 138, 1285–1294. doi:10.1038/sj.bjp.0705168
Peroxisome proliferator‐activated receptor α is involved in the regulation of lipid metabolism by ginseng
Authors: Yoon Michung , Lee Hyunghee , Jeong Sunhyo , Kim Jung‐Jae , Nicol Christopher J , Nam Kung Woo , Kim Moonza , Cho Byung Goo , Oh Goo Taeg 
Published: April 2003

Peroxisome proliferator‐activated receptor α (PPARα) regulates the expression of the key genes involved in lipid metabolism following activation of this receptor by various ligands. Ginseng, a highly valuable medicine in oriental societies, is also reported to modulate lipid metabolism, although the mechanism of its action remains unknown. In order to test our hypothesis that ginseng exerts its effects by altering PPARα‐mediated pathways, the effects of Korean red ginseng on PPARα function and serum lipid profiles were investigated using in vivo and in vitro approaches.
In vivo administration of ginseng extract (GE) and ginsenosides (GS) not only inhibited mRNA levels of acyl‐CoA oxidase, a rate‐limiting enzyme for PPARα‐mediated peroxisomal fatty acid β‐oxidation, induced by the potent PPARα ligand Wy14,643 in a dose‐ and time‐dependent manner, but also inhibited the induction of PPARα target genes expected following treatment with Wy14,643.
Consistent with the in vivo data, both GE and GS caused dose‐dependent decreases in the endogenous expression of a luciferase reporter gene containing the PPAR responsive element (PPRE), while GS significantly decreased the magnitude of reporter gene activation in the presence of Wy14,643.
Serological studies demonstrated that, compared with vehicle‐treated mice, treatment with GS significantly increased serum concentrations of total cholesterol, triglycerides, and high‐density lipoprotein (HDL) cholesterol. Compared to groups treated with Wy14,643 alone, which significantly decreased serum triglyceride and HDL cholesterol levels versus controls, coadministration of either GE or GS with Wy14,643 modestly increased serum triglycerides and HDL cholesterol.
These results indicate that the effects of ginseng on serum lipid profiles may be mediated by changes in the expression of PPARα target genes, providing the first evidence that in vivo and in vitro treatments of ginseng modulate PPARα action. In addition, these data suggest that ginseng can act as an inhibitor of PPARα function, which may have therapeutic implications.

British Journal of Pharmacology (2003) 138, 1295–1302. doi:10.1038/sj.bjp.0705169
Actions of bradykinin on electrical and synaptic behavior of neurones in the myenteric plexus of guinea‐pig small intestine
Authors: Hu Hong‐Zhen , Liu Sumei , Gao Na , Xia Yun , Mostafa Randa , Ren Jun , Zafirov Dimiter H , Wood Jackie D 
Published: April 2003

Electrophysiologic methods were used to study actions of bradykinin (BK) in neurones of the myenteric plexus of guinea‐pig small intestine in vitro. Exposure to BK depolarized the membrane potential and elevated excitability in AH‐ and S‐type neurones. Neuronal input resistance associated with the depolarizing responses was either decreased or unchanged in S‐type and increased in AH‐type neurones.
The selective B2 BK receptor antagonist HOE‐140, but not the selective B1 receptor antagonist des‐arg10‐HOE‐140, suppressed the BK‐evoked responses. RT‐PCR confirmed the expression of B2 receptor mRNA, but not B1 receptor mRNA.
Binding of fluorescently‐ labeled HOE‐140 (HOE741) was localized to ganglion cells in whole‐mount preparations. BK B2 receptors were coexpressed with immunoreactivity for calbindin or nitric oxide synthase.
Exposure to BK suppressed the amplitude of both fast and slow excitatory postsynaptic potentials. Depolarizing responses evoked by application of serotonin or substance P and nicotinic responses to acetylcholine were not reduced by BK. This suggested that BK action on neurotransmission was presynaptic suppression of neurotransmitter release. Presence of HOE‐140 in the bathing solution suppressed or abolished the presynaptic inhibitory action of BK.
The cyclooxygenase inhibitor, piroxicam, suppressed both the direct excitatory action of BK and its presynaptic inhibitory action. Application of prostaglandin E2, D2, F2α or I2 mimicked the BK‐evoked responses.
The results suggest that BK acts at B2 BK receptors on myenteric neurones to stimulate the formation of prostaglandins. Once formed and released, the prostaglandins act to elevate the excitability of ganglion cells in the myenteric plexus and to suppress the synaptic release of neurotransmitters.

British Journal of Pharmacology (2003) 138, 1221–1232. doi:10.1038/sj.bjp.0705180
A novel immunosuppressive agent FTY720 induced Akt dephosphorylation in leukemia cells
Authors: Matsuoka Yumiko , Nagahara Yukitoshi , Ikekita Masahiko , Shinomiya Takahisa 
Published: April 2003

Our previous studies revealed that the immunosuppressive agent, FTY720, mainly induces mitochondria‐involved apoptosis in some types of cancer cells, since Bcl‐2 overexpression prevents the FTY720‐induction of apoptotic stimuli. Furthermore, FTY720 induces G0/G1 cell cycle arrest. The present study further examines the correlation between intracellular signaling kinases with FTY720‐induced mitochondria‐involved apoptosis.
Human T cell leukemia Jurkat was exposed to FTY720. Dephosphorylation of Akt occurred in a time‐ and concentration‐dependent manner. FTY720 also induced Bad (Ser136) and ribosomal p70S6 kinase (p70S6k) (Thr389) dephosphorylation.
FTY720‐induced Akt dephosphorylation was not because of Akt upstream phosphatidylinositol 3′‐kinase (PI 3‐kinase) pathway inhibition.
FTY720 also induced Akt dephosphorylation in human B cell leukemia BALL‐1. BALL‐1 cells were resistant to FTY720‐induced apoptosis.
Okadaic acid (OA) inhibited the FTY720‐induced dephosphorylation of Akt and p70S6k, suggesting that FTY720 promotes Ser/Thr protein phosphatase (PP) activity.
OA partially inhibited FTY720‐induced caspase‐3 activation.
PP2A or PP2A‐like phosphatase was temporarily activated in cells exposed to FTY720. In addition, FTY720 activated purified PP2A (ABC).
Overall, the results suggest that FTY720 activated PP2A or PP2A‐like phosphatase and dephosphorylated Akt pathway factors resulting in the enhancement of apoptosis via mitochondria.

British Journal of Pharmacology (2003) 138, 1303–1312. doi:10.1038/sj.bjp.0705182
Phorbol esters and neurotransmitter release: more than just protein kinase C?
Authors: Silinsky Eugene M , Searl Timothy J 
Published: April 2003

This review focuses on the effects of phorbol esters and the role of phorbol ester receptors in the secretion of neurotransmitter substances. We begin with a brief background on the historical use of phorbol esters as tools to decipher the role of the enzyme protein kinase C in signal transduction cascades. Next, we illustrate the structural differences between active and inactive phorbol esters and the mechanism by which the binding of phorbol to its recognition sites (C1 domains) on a particular protein acts to translocate that protein to the membrane. We then discuss the evidence that the most important nerve terminal receptor for phorbol esters (and their endogenous counterpart diacylglycerol) is likely to be Munc13. Indeed, Munc13 and its invertebrate homologues are the main players in priming the secretory apparatus for its critical function in the exocytosis process.British Journal of Pharmacology (2003) 138, 1191–1201. doi:10.1038/sj.bjp.0705213
Effects of bioaerosol polluted outdoor air on airways of residents: a cross sectional study
Authors: Herr C E W , zur Nieden A , Jankofsky M , Stilianakis N I , Boedeker R-H , Eikmann T F 
Published: April 2003

Background:Bioaerosol pollution of workplace and home environments mainly affects airways and mucous membranes. The effect of environmental outdoor residential bioaerosol pollution, for example, livestock holdings, farming, and waste disposal plants, is unclear.Aims:To investigate the perceived health of residents living in areas with measurable outdoor bioaerosol pollution (for example, spores ofAspergillus fumigatusand actinomycetes), and effects of accompanying odours.Methods:In a cross sectional study, double blinded to ongoing microbial measurements, doctors collected 356 questionnaires from residents near a large scale composting site, and from unexposed controls in 1997. Self reported prevalence of health complaints during the past year, doctors’ diagnoses, as well as residential odour annoyance were assessed. Microbiological pollution was measured simultaneously in residential outdoor air.Results:Concentrations of >105colony forming units of thermophilic actinomycetes, moulds, and total bacteria/m3air were measured 200 m from the site, dropping to near background concentrations within 300 m. Positive adjusted associations were observed for residency within 150–200 m from the site versus unexposed controls for self reported health complaints: “waking up due to coughing”, odds ratio (OR) 6.59 (95% confidence interval (CI) 2.57 to 17.73); “coughing on rising or during the day”, OR 3.18 (95% CI 1.24 to 8.36); “bronchitis”, OR 3.59 (95% CI 1.40 to 9.4); and “excessive tiredness”, OR 4.27 (95% CI 1.56 to 12.15). Reports of irritative airway complaints were associated with residency in the highest bioaerosol exposure, 150–200 m (versus residency >400–500 m) from the site, and period of residency more than five years, but not residential odour annoyance. Lifetime prevalence of self reported diseases did not differ with exposure.Conclusions:Bioaerosol pollution of residential outdoor air can occur in concentrations found in occupational environments. For the first time residents exposed to bioaerosol pollution were shown to report irritative respiratory complaints similar to mucous membrane irritation independently of perceived odours.
One year effectiveness of an individualised smoking cessation intervention at the workplace: a randomised controlled trial
Authors: Rodríguez-Artalejo F , Lafuente Urdinguio P , Guallar-Castillón P , Garteizaurrekoa Dublang P , Sáinz Martínez O , Díez Azcárate J I , Foj Alemán M , Banegas J R 
Published: April 2003

Aims:To assess the effectiveness of a smoking cessation intervention at the workplace. The intervention was adapted to smokers‘ tobacco dependence, and included minimal structured counselling at the first visit (5–8 minutes), nicotine patches for three months, and three sessions of counselling for reinforcement of abstinence (2–3 minutes) over a three month period.Methods:Open randomised trial with two groups: the intervention group, and the control group which was subjected to standard clinical practice, consisting of short (30 seconds to one minute) sporadic sessions of unstructured medical antismoking advice. The trial was carried out among 217 smokers of both sexes, aged 20–63 years, motivated to quit smoking and without contraindications for nicotine patches, who were employees at a public transport company and at two worksites of an electric company. The main outcome measure was self reported tobacco abstinence confirmed by carbon monoxide in expired air ≤10 ppm. Analysis was performed according to intention-to-treat.Results:The rate of continuous abstinence at 12 months was 20.2% for the intervention versus 8.7% for the control group (OR: 2.58; 95% CI: 1.13 to 5.90; p = 0.025). In subgroup analyses, effectiveness of the intervention did not vary substantially with age, tobacco dependence, number of cigarettes smoked per day, number of years of tobacco consumption, degree of desire to quit smoking, time spent with smokers, subjective health, and presence of tobacco related symptoms. Weight gain at 12 months was similar for both groups (1.69 kg in the interventionv2.01 kg in the control group; p = 0.21).Conclusions:A simple and easily generalisable intervention at the workplace is effective to achieve long term smoking cessation. In a setting similar to ours, nine subjects would have to be treated for three months for one to achieve continuous abstinence for 12 months.
Medical staff in emergency situations: severity of patient status predicts stress hormone reactivity and recovery
Authors: Sluiter J K , van der Beek A J , Frings-Dresen M H W 
Published: April 2003

Background:Although repetitive exposure to stressful situations is thought to habituate the physical stress responses, work stress is experienced by medical personnel in emergency and intensive care units; performance should, however, remain stable over time.Aims:To investigate the neuroendocrine reactions (reactivity during and recovery after work) in experienced emergency caregivers during emergency situations.Methods:A within subjects pre-post design was studied in the natural work environment of 20 municipal Dutch emergency caregivers. A stress protocol was developed in which the biomarker cortisol was measured in saliva at baseline, during the emergency period, and during recovery. Four scenarios were tested between subjects in which the severity of the emergency situation and the time of day were taken into account.Results:Greater endocrine reactions were shown during and after the handling of patients in direct life threatening situations during morning hours compared to the handling of patients who were not in direct life threatening situations.
WORLDLINE SUPERFIELD ACTIONS FOR N=2 SUPERPARTICLES
Authors: BANDOS IGOR , SOROKIN DMITRI , MAZNYTSIA ALEXEY 
Published: April 2003

We propose doubly supersymmetric actions in terms of n=2(D-2) worldline superfields for N=2 superparticles in D=3,4 and type IIA D=6 superspaces. These actions are obtained by dimensional reduction of superfield actions for N=1 superparticles in D=4,6,10, respectively. We show that in all these models geometrodynamical constraints on target-superspace coordinates do not put the theory on the mass shell, and so the actions constructed consistently describe the dynamics of the corresponding N=2 superparticles. We also find that, in contrast to the IIA D=6 superparticle, a chiral IIB D=6 superparticle, which is not obtainable by dimensional reduction from N=1, D=10, is described by superfield constraints which produce dynamical equations. This implies that for the IIB D=6 superparticle the doubly supersymmetric action does not exist in the conventional form.
THE ABELIAN HIGGS MODEL AS AN ENSEMBLE OF VORTEX LOOPS
Authors: ANTONOV DMITRI 
Published: April 2003

In the London limit of the Ginzburg–Landau theory (Abelian Higgs model), vortex dipoles (small vortex loops) are treated as a grand canonical ensemble in the dilute gas approximation. The summation over these objects with the most general rotation and translation-invariant measure of integration over their shapes leads to effective sine–Gordon theories of the dual fields. The representations of the partition functions of both grand canonical ensembles are derived in the form of the integrals over the vortex dipoles and the small vortex loops, respectively. By virtue of these representations, the bilocal correlator of the vortex dipoles (loops) is calculated in the low-energy limit. It is further demonstrated that once the vortex dipoles (loops) are considered as such an ensemble rather than individual ones, the London limit of the Ginzburg–Landau theory (Abelian Higgs model) with external monopoles is equivalent up to the leading order in the inverse UV cutoff to the compact QED in the corresponding dimension with the charge of Cooper pairs changed due to the Debye screening.
A LOAD-BALANCED ALGORITHM FOR PARALLEL DIGITAL IMAGE WARPING
Authors: CONTASSOT-VIVIER SYLVAIN , MIGUET SERGE 
Published: April 2003

This paper introduces and compares three parallel algorithms to compute general geometric image transformations on MIMD machines. We propose three variants of a parallel general scheme. We focus on the load balancing and the data redistributions. Experimental results are reported and compared. The implementation has been done using PPCM library allowing us to run the program over different parallel machines. We compare logical communication schemes for message-passing machines. Since our parallel algorithm needs global communications such as multiscatters, we study the efficiency of two different logical topologies usable with PPCM. These studies allow us to find the best combination of algorithm and virtual topology to use on a given parallel machine.
Assessment of an Age-Adjusted Warfarin Initiation Protocol
Authors: Roberts Gregory W , Helboe Trine , Nielsen Cathrine BM , Gallus Alex S , Jensen Iwona , Cosh David G , Eaton Vaughn S 
Published: April 2003

OBJECTIVE: To examine the time taken to reach a stable international normalized ratio (INR), as well as the incidence of overanticoagulation of an age-adjusted warfarin initiation protocol. METHODS: Inpatients and outpatients commencing warfarin therapy at 2 teaching hospitals were dosed according to the age-adjusted protocol. Data were collected prospectively. MAIN OUTCOME MEASURES: Time to reach a stable INR of 2–3 and the number of patients experiencing an INR ≥4 during the first week of warfarin therapy. RESULTS: Seventy-three patients were assessed; at the completion of the 4-day titration protocol, 63% had achieved a stable INR. After an additional 2 days of empiric dosage adjustment by the attending physician, 86% of the subjects demonstrated a stable INR. Five patients (7%) experienced an INR ≥4. These patients had a nonsignificant trend toward a lower plasma albumin level compared with other patients (p = 0.057, Student's t-test). The INR-driven dose adjustments on days 3 and 4 of this protocol coped with other variables that have been shown to affect maintenance warfarin dosing. These included weight, gender, pharmacologic factors affecting clearance, and the presence of certain predesignated risk factors. CONCLUSIONS: The age-adjusted dosing protocol rapidly achieved a stable INR with minimal overanticoagulation. Patients with low serum albumin levels (<3.0 g/dL) may be sensitive to the effects of warfarin during the loading phase.