bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability of Computerized Emergency Triage
Authors: Dong Sandy L. , Bullard Michael J. , Meurer David P. , Blitz Sandra , Ohinmaa Arto , Holroyd Brian R. , Rowe Brian H. 
Published: February 2006

Objectives:
Emergency department (ED) triage prioritizes patients based on urgency of care. This study compared agreement between two blinded, independent users of a Web‐based triage tool (eTRIAGE) and examined the effects of ED crowding on triage reliability.
Methods:
Consecutive patients presenting to a large, urban, tertiary care ED were assessed by the duty triage nurse and an independent study nurse, both using eTRIAGE. Triage score distribution and agreement are reported. The study nurse collected data on ED activity, and agreement during different levels of ED crowding is reported. Two methods of interrater agreement were used: the linear‐weighted κ and quadratic‐weighted κ.
Results:
A total of 575 patients were assessed over nine weeks, and complete data were available for 569 patients (99.0%). Agreement between the two nurses was moderate if using linear κ (weighted κ= 0.52; 95% confidence interval = 0.46 to 0.57) and good if using quadratic κ (weighted κ= 0.66; 95% confidence interval = 0.60 to 0.71). ED overcrowding data were available for 353 patients (62.0%). Agreement did not significantly differ with respect to periods of ambulance diversion, number of admitted inpatients occupying stretchers, number of patients in the waiting room, number of patients registered in two hours, or nurse perception of busyness.
Conclusions:
This study demonstrated different agreement depending on the method used to calculate interrater reliability. Using the standard methods, it found good agreement between two independent users of a computerized triage tool. The level of agreement was not affected by various measures of ED crowding.
Acetylation of Estrogen Receptor α by p300 at Lysines 266 and 268 Enhances the Deoxyribonucleic Acid Binding and Transactivation Activities of the Receptor
Authors: Kim Mi Young , Woo Eileen M. , Chong Yee Ting Esther , Homenko Daria R. , Kraus W. Lee 
Published: February 2006

AbstractUsing a variety of biochemical and cell-based approaches, we show that estrogen receptor α (ERα) is acetylated by the p300 acetylase in a ligand- and steroid receptor coactivator-dependent manner. Using mutagenesis and mass spectrometry, we identified two conserved lysine residues in ERα (Lys266 and Lys268) that are the primary targets of p300-mediated acetylation. These residues are acetylated in cells, as determined by immunoprecipitation-Western blotting experiments using an antibody that specifically recognizes ERα acetylated at Lys266 and Lys268. The acetylation of ERα by p300 is reversed by native cellular deacetylases, including trichostatin A-sensitive enzymes (i.e. class I and II deacetylases) and nicotinamide adenine dinucleotide-dependent/nicotinamide-sensitive enzymes (i.e. class III deacetylases, such as sirtuin 1). Acetylation at Lys266 and Lys268, or substitution of the same residues with glutamine (i.e. K266/268Q), a residue that mimics acetylated lysine, enhances the DNA binding activity of ERα in EMSAs. Likewise, substitution of Lys266 and Lys268 with glutamine enhances the ligand-dependent activity of ERα in a cell-based reporter gene assay. Collectively, our results implicate acetylation as a modulator of the ligand-dependent gene regulatory activity of ERα. Such regulation is likely to play a role in estrogen-dependent signaling outcomes in a variety of estrogen target tissues in both normal and pathological states.
In-vitro and in-vivo characterization of a buprenorphine delivery system
Authors: Kleppner Sofie R , Patel Raj , Costantini Lauren C , McDonough Joseph 
Published: February 2006

Abstract
Buprenorphine is a mu-opioid receptor partial agonist with enhanced safety and comparable efficacy to methadone for treatment of opioid dependence. The sublingual formulation of buprenorphine, approved for treatment of opioid dependence, produces variable buprenorphine blood levels and requires frequent dosing that limits patient compliance. To achieve stable buprenorphine levels that may improve patient outcome, an implantable sustained buprenorphine delivery system was developed. Each implant consists of ethylene vinyl acetate copolymer and 90 mg buprenorphine HCl, and measures 26 mm in length and 2.4 mm in diameter. Steady-state release in-vitro was 0.5 mg/implant/day. In-vivo pharmacokinetics and safety were examined for up to 52 weeks in beagle dogs receiving 8, 16 or 24 subcutaneous implants. Plasma buprenorphine concentrations correlated with the number of implants administered. Peak buprenorphine concentrations were generally reached within 24 h after implantation. Steady-state plasma levels were attained between 3 and 8 weeks, and were maintained for study duration, with a calculated mean release rate of 0.14 ± 0.04 mg/implant/day. There were no test-article-related adverse effects. This delivery system can provide long-term stable systemic buprenorphine levels, and may increase patient compliance, thereby improving outcome for opioid-dependent patients.
Chitosan nanoparticles encapsulated vesicular systems for oral immunization: preparation, in-vitro and in-vivo characterization
Authors: Jain Sanyog , Sharma Rakesh Kumar , Vyas S P 
Published: February 2006

Abstract
BSA-loaded chitosan nanoparticles were prepared and encapsulated in vesicles (liposomes and nio-somes) to make them acid resistant upon oral administration. Prepared systems were characterized in-vitro for shape, size, entrapment efficiency and stability in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.5). The immune stimulating activity was studied by measuring serum IgG titre and secretory IgA (sIgA) levels in mucosal secretions following oral administration of various formulations in albino rats. Significantly higher (P &lt; 0.05) serum IgG titres were achieved following oral administration of novel nanoparticulate vesicular formulations as compared with unmodified chitosan nanoparticles. Further, high sIgA levels in mucosal secretions advocated a possible application of chitosan nanoparticle encapsulated in vesicles as an oral vaccine delivery carrier-adjuvant system.
Arthritis and cannabinoids: HU-210 and Win-55,212–2 prevent IL-1 α-induced matrix degradation in bovine articular chondrocytes in-vitro
Authors: Mbvundula Estery C , Bunning Rowena A D , Rainsford K D 
Published: February 2006

AbstractCannabinoids have analgesic, immunomodulatory and anti-inflammatory properties and attenuate joint damage in animal models of arthritis. In this study the mechanisms of action of the synthetic cannabinoid agonists, HU-210 and Win-55,212–2, were studied to determine if they affected interleukin-1 alpha (IL-1α)-induced proteoglycan and collagen degradation in bovine nasal cartilage explant cultures and prostaglandin E2 (PGE2) production in primary cultures of bovine articular chondrocytes. The effects of the inactive enantiomer, Win-55,212–3, were compared with those of the active enantiomer, Win-55,212–2, to determine if the effects were cannabinoid (CB)-receptor mediated. The chondrocytes and explants were stimulated by IL-1α (100 U mL−1 ≡ 0.06 nm and 500 U mL−1 ≡ 0.3 nm, respectively). Proteoglycan breakdown was determined as sulfated glycosaminoglycan (sGAG) release using the dimethylmethylene blue assay. Collagen degradation was determined as hydroxyproline in the conditioned culture media and cartilage digests. PGE2 was determined by ELISA. Expression of cannabinoid receptors, CB1 and CB2; cyclooxygenase-1 and −2 (COX-1 and COX-2); inducible nitric oxide synthase (iNOS); as well as activation of nuclear factor-kappa B (NF-κB) in chondrocytes were studied using immunoblotting techniques and immunofluorescence. The results showed that HU-210 and Win-55,212–2 (5–15 μm) significantly inhibited IL-1α-stimulated proteoglycan (P &lt; 0.001) and collagen degradation (P &lt; 0.001). Win-55,212–2 (5–10 μm) also significantly inhibited PGE2 production (P &lt; 0.01). At 5 μm, Win-55,212–2 inhibited the expression of iNOS and COX-2 and activation of NF-κB. Chondrocytes appeared to constitutively express cannabinoid receptors CB1 and CB2. It is concluded that biologically stable synthetic cannabinoids protect cartilage matrix from degradation induced by cytokines and this effect is possibly CB-receptor mediated and involves effects on prostaglandin and nitric oxide metabolism. Cannabinoids could also be producing these effects via inhibition of NF-κB activation.
Suppression of matrix metalloproteinase production from synovial fibroblasts by meloxicam in-vitro
Authors: Asano Kazuhito , Sakai Misako , Matsuda Takako , Tanaka Hironori , Fujii Keigo , Hisamitsu Tadashi 
Published: February 2006

Abstract
The aim of this study was to evaluate the influence of meloxicam on the production of both matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) from human synovial fibroblasts by TNF-α stimulation in-vitro. Synovial fibroblasts (2 times 104 cells/mL) derived from patients with osteoarthritis were stimulated with 20.0 ng mL−1 TNF-α in the presence of various concentrations of meloxicam. After 24 h, the culture supernatants were obtained and assayed for MMP-1, MMP-2, MMP-3, MMP-13, TIMP-1 and TIMP-2 by ELISA. mRNA expression for MMPs and TIMPs in 4-h-cultured cells were examined by real-time polymerase chain reaction. Transcriptional factor (NF-κB and AP-1) activation in 2-h-cultured cells was also examined by ELISA. Meloxicam could suppress MMP production in a dose-dependent manner. The minimum concentration of the agent that showed significant suppression was 0.6 times 10−6 m for MMP-1, MMP-2 and MMP-3, and 1.3 times 10−6 m for MMP-13. The ability of synovial fibroblasts to produce TIMPs was also suppressed by meloxicam as in the case of MMP production. Addition of meloxicam into synovial fibroblast cultures inhibited dose-dependently mRNA expression for MMPs and TIMPs, which were increased by TNF-α stimulation, through the suppression of NF-κB and AP-1 activation. The suppressive effect of meloxicam on the production of MMPs and TIMPs may partly be involved in attenuation of the clinical conditions of osteoarthritis and rheumatoid arthritis.
Acute and long-term administration of citalopram desensitizes α2-adrenoceptors in the rat vas deferens
Authors: Grandoso Laura , García Laura , Pineda Joseba , Ugedo Luisa 
Published: February 2006

AbstractThe aim of this study was to investigate the effect of citalopram, a selective serotonin reuptake inhibitor, on the sensitivity of rat vas deferens α2-adrenoceptors and to compare it with the effects of serotonin and the dual noradrenaline-serotonin uptake inhibitor duloxetine. To this end, we studied the inhibitory effect of the α2-adrenoceptor agonist bromoxidine on the electrically induced contraction of the vas deferens. Citalopram (1, 3 times 103 and 3 times 104 nm) applied in-vitro significantly attenuated the concentration-response inhibition induced by activation of α2-adrenoceptors on the electrically evoked contraction of the vas deferens (concentration of the agonist required to promote 50% of the maximal effect, EC50, for bromoxidine increased by 232%, 421% and 818%, respectively). Similarly, serotonin also attenuated the concentration-response inhibition mediated by presynaptic α2-adrenoceptors (96% increase in EC50). Acute and long-term systemic administration of citalopram and duloxetine also produced a loss in the sensitivity of α2-adrenoceptors to bromoxidine (EC50 for bromoxidine increased by 97% and 144%, respectively, after citalopram, and by 214% and 167% after duloxetine). In addition, we observed that an increased fraction of receptors was required to be occupied to yield 50% of the inhibitory effect of bromoxidine after long-term administration of citalopram and duloxetine (KE increased by 142% and 83%). These results are indicative of early-onset and persistent down-regulation of peripheral α2-adrenoceptors by citalopram, which may account for some of its side effects.
Different anticonvulsive effects of hesperidin and its aglycone hesperetin on electrical activity in the rat hippocampus in-vitro
Authors: Dimpfel Wilfried 
Published: February 2006

Abstract
This study investigated the possibility that hesperidin or hesperetin might interact directly with brain matter in a physiological manner. The effects of both compounds were followed in the in-vitro hippocampus preparation by continuous superfusion in a concentration-dependent manner in the presence of single stimuli and theta-burst stimulation of the Schaffer Collaterals. Hesperidin increased the population spike response at a concentration up to 10 μm, especially after induction of long-term potentiation, but attenuated it significantly at higher concentrations of up to 60 μm. Hesperetin only attenuated the response within the same concentration range. Modulation of the pyramidal cell response in the presence of tetraethylammonium (TEA) and pentylentetrazol on one hand and 4-aminopyridine (4-AP) and bicuculline on the other was influenced in a different way. Whereas hesperidin attenuated the response to 4-AP and bicuculline but not to TEA or pentylentetrazol, hesperetin was able to attenuate the response to TEA and pentylentetrazol, but not to 4-AP or bicuculline. This feature was reproduced and confirmed ex-vivo after repetitive administration of hesperidin and hesperetin in-vivo for one week (500 mg kg−1 orally) before in-vitro testing against the challenging effects of 4-AP and TEA. Since the action of hesperidin was sensitive to the presence of iberiotoxin, the involvement of a large conductance calcium-dependent potassium channel might be assumed. In summary, the results provide the possibility for use of both compounds to control pathophysiological disturbances of brain excitability in drug abuse, migraine and epilepsy.
Inhibition of rat vas deferens contractions by flavonoids in-vitro
Authors: Capasso Raffaele , Ascione Valeria , Borrelli Francesca , Fiorino Ferdinando , Frecentese Francesco 
Published: February 2006

Abstract
Flavonoids are a large heterogeneous group of benzo-γ-pyrone derivatives, which are abundantly present in our diet. In this study we investigated the effect of ten flavonoids (quercetin, kaempferol, morin, galangin, rutin, apigenin, flavone, naringenin, hesperitin and silybin) on the contractile response elicited by electrical field stimulation in the rat isolated vas deferens. All flavonoids tested inhibited vas deferens contractions. The relative order of potency of the tested flavonoids was naringenin &gt; hesperitin &gt; morin &gt; kaempferol &gt; apigenin &gt; silybin &gt; flavone &gt; rutin &gt; quercetin &gt; galangin. Analysis of the chemical structures showed that the saturation of C-2-C-3 double bond and the presence of hydroxyl groups on the flavonoidic scaffold play an important role in the activity of flavonoids.
Synthesis and evaluation of N-(3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-1H-indole-carboxamides as cholecystokinin antagonists
Authors: Lattmann Eric , Singh Harjit , Lattmann Pornthip , Boonprakob Yodchai , Sattayasai Jintana 
Published: February 2006

Abstract
The structure-activity relationship optimization of the pyrazoline template 3a resulted in novel 3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-indole carboxamides 4a–4e. These non-peptidal CCK ligands have been shown to act as potent CCK1 ligands in a [125]I-CCK-8 receptor binding assay. The best amides (4c and 4d) of this series displayed an IC50 of 20/25 nm for the CCK1 receptor. In a subsequent in-vivo evaluation using various behaviour pharmacological assays, an anxiolytic effect of these novel 3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-indole carboxamides was found at high doses in the elevated plus-maze. In the despair swimming test, a model for testing antidepressants, an ED50 of 0.33/0.41 mg kg−1 was determined for amide 4c/4d and the antidepressant effect had a magnitude comparable to desimipramine.
Metabolism of nicotine in rat lung microvascular endothelial cells
Authors: Ochiai Yoshinori , Itoh Kunio , Tanaka Yorihisa , Sakurai Eiichi , Nomura Akio 
Published: February 2006

AbstractThe aim of this study was to examine whether cultured rat lung microvascular endothelial cells (LMECs), which constitute the gas-blood barrier, have the ability to metabolize nicotine. Nicotine was biotransformed to cotinine and nicotine N′-oxide by cytochrome 450 (CYP) and flavin-containing monooxyganase (FMO), respectively, in rat LMECs. The intrinsic clearance (Vmax1/Km1) for the cotinine formation was about 20 times as high as that for the trans-nicotine N′-oxide formation in the low-Km phase, indicating that oxidation by CYP was much higher than that by FMO. On the other hand, as shown in Eadie-Hofstee plots, the formation of cis-nicotine N′-oxide was monophasic, whereas the plot for the trans-nicotine N′-oxide formation was clearly biphasic. These results suggest that nicotine N′-oxide was stereoselectively metabolized to cis and trans forms. However, in the high-Km phase there was no significant difference in N′-oxidation between the cis and trans forms. Moreover, we suggest that CYP2C11 and CYP3A2 are key players in the metabolism to cotinine of nicotine in rat LMECs using the respective enzyme inhibitors (tranylcypromine and troleandomycine). On the other hand, methimazole (5 μm) caused 73 and 45% decreases in the formation of N′-oxides of cis- and trans- enantiomers, respectively, demonstrating the presence of FMO in rat LMECs. These results suggest that rat LMEC enzymes can convert substrates of exogenous origin such as nicotine for detoxication, indicating LMECs are an important barrier for metabolic products, besides hepatic cells.
The novel application of tertiary butyl alcohol in the preparation of hydrophobic drug-HPβCD complex
Authors: Wang Zhixuan , Deng Yingjie , Zhang Xiaopeng 
Published: February 2006

Abstract
This report describes a novel application of tertiary butyl alcohol (TBA) in the preparation of hydrophobic drug-hydroxypropyl β-cyclodextrin (HPβCD) complex. The straightforward, economic preparation procedure consists of dissolving both the hydrophobic drug and HPβCD in TBA, which is subsequently freeze-dried to give the hydrophobic drug-HPβCD complex in the form of a porous powder. TBA was selected as the medium due to it being a good solvent for hydrophobic drug and HPβCD; in addition, it is also a versatile lyophilization medium and is widely used in pharmaceutical processes. In this study, ketoprofen and nitrendipine were used as model drugs and their HPβCD complexes were prepared by lyophilization of the TBA system. Based on the data from differential scanning calorimetry (DSC) and X-ray diffractometry (XRD), the drugs were amorphous in freeze-dried samples. The infra-red (IR) spectrum indicated that a drug-HPβCD interaction took place in the freeze-dried complex. Dissolution experiments showed that the hydrophobic drug dissolved rapidly from the HPβCD complex in both simulated gastric juice and simulated intestinal fluid. These results confirmed that this technique produced a hydrophobic drug-HPβCD complex. TBA was found to be a suitable freeze-drying medium for the preparation of hydrophobic drug-HPβCD complex. This approach is versatile, energy-conserving and can easily be scaled up. It is expected to have further application in modifying the physicochemical characteristics of hydrophobic drugs and improving their absorption and pharmacodynamic properties.
A Nonparametric Approach to Multiproduct Pricing
Authors: Rusmevichientong Paat , Van Roy Benjamin , Glynn Peter W. 
Published: February 2006

Developed by General Motors (GM), the Auto Choice Advisor website ( http://www.autochoiceadvisor.com ) recommends vehicles to consumers based on their requirements and budget constraints. Through the website, GM has access to large quantities of data that reflect consumer preferences. Motivated by the availability of such data, we formulate a nonparametric approach to multiproduct pricing. We consider a class of models of consumer purchasing behavior, each of which relates observed data on a consumer’s requirements and budget constraint to subsequent purchasing tendencies. To price products, we aim at optimizing prices with respect to a sample of consumer data. We offer a bound on the sample size required for the resulting prices to be near-optimal with respect to the true distribution of consumers. The bound exhibits a dependence of O(n log n) on the number n of products being priced, showing that—in terms of sample complexity—the approach is scalable to large numbers of products. With regards to computational complexity, we establish that computing optimal prices with respect to a sample of consumer data is NP-complete in the strong sense. However, when prices are constrained by a price ladder—an ordering of prices defined prior to price determination—the problem becomes one of maximizing a supermodular function with real-valued variables. It is not yet known whether this problem is NP-hard. We provide a heuristic for our price-ladder-constrained problem, together with encouraging computational results. Finally, we apply our approach to a data set from the Auto Choice Advisor website. Our analysis provides insights into the current pricing policy at GM and suggests enhancements that may lead to a more effective pricing strategy.
Managing Patient Service in a Diagnostic Medical Facility
Authors: Green Linda V. , Savin Sergei , Wang Ben 
Published: February 2006

Hospital diagnostic facilities, such as magnetic resonance imaging centers, typically provide service to several diverse patient groups: outpatients, who are scheduled in advance; inpatients, whose demands are generated randomly during the day; and emergency patients, who must be served as soon as possible. Our analysis focuses on two interrelated tasks: designing the outpatient appointment schedule, and establishing dynamic priority rules for admitting patients into service.We formulate the problem of managing patient demand for diagnostic service as a finite-horizon dynamic program and identify properties of the optimal policies. Using empirical data from a major urban hospital, we conduct numerical studies to develop insights into the sensitivity of the optimal policies to the various cost and probability parameters and to evaluate the performance of several heuristic rules for appointment acceptance and patient scheduling.
Transforming growth factor-beta (TGF-β) in acute injuries of the spinal cord
Authors: Quinlan J. F. , Watson R. W. G. , Kelly G. , Kelly P. M. , O’Byrne J. M. , Fitzpatrick J. M. 
Published: February 2006

Injuries to the spinal cord may be associated with increased healing of fractures. This can be of benefit, but excessive bone growth can also cause considerable adverse effects. We evaluated two groups of patients with fractures of the spinal column, those with neurological compromise (n = 10) and those without (n = 15), and also a control group with an isolated fracture of a long bone (n = 12). The level of transforming growth factor-beta (TGF-β), was measured at five time points after injury (days 1, 5, 10, 42 and 84). The peak level of 142.79 ng/ml was found at day 84 in the neurology group (p < 0.001 vs other time points). The other groups peaked at day 42 and had a decrease at day 84 after injury (p ≤ 0.001). Our findings suggest that TGF-β may have a role in the increased bone turnover and attendant complications seen in patients with acute injuries to the spinal cord.