UK PubMed Central (United Kingdom)

BackgroundWe investigated whether p42/p44 extracellular signal-regulated kinases (ERK1/2) and/or phosphatidylinositol-3-OH kinase (PI3K)-Akt play a crucial role in cardioprotection...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

(3H)Cyclofoxy (CF: 17-cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta-fluoromorp hinan) is an opioid antagonist with affinity to both mu and kappa subtypes that was synthesized for quantitative evaluation of opioid receptor binding in vivo. Two sets of experiments in rats were analyzed. The first involved determining the metabolite-corrected blood concentration and tissue distribution of CF in brain 1 to 60 min after i.v. bolus injection. The second involved measuring brain washout for 15 to 120 s following intracarotid artery injection of CF. A physiologically based model and a classical compartmental pharmacokinetic model were compared. The models included different assumptions for transport across the blood-brain barrier (BBB); estimates of nonspecific tissue binding and specific binding to a single opiate receptor site were found to be essentially the same with both models. The nonspecific binding equilibrium ...

UK PubMed Central (United Kingdom)

ContextWhile opioids are increasingly used for chronic non-cancer pain (CNCP), we know little about opioid dosing patterns among individuals with CNCP in usual care...Full Text Available

UK PubMed Central (United Kingdom)

ABSTRACTOBJECTIVETo explore the prevalence and the demographic predictors of nonmedical use of opioid analgesics in the Canadian adolescent population.DESIGNData...Full Text Available

International Nuclear Information System (INIS)

The inducible transcription factor NF-#kappa#B regulates divergent signaling pathways including inflammatory response and cancer development. Selective inhibitors for NF-#kappa#B signaling are potentially useful for treatment of inflammation and cancer. NF-#kappa#B is canonically activated by preferential disposal of its inhibitory protein; I#kappa#B, which suppresses the nuclear translocation of NF-#kappa#B. I#kappa#B#alpha# (a major member of I#kappa#B family proteins) is phosphorylated with an I#kappa#B kinase (IKK) and subsequently polyubiquitylated by SCF"#beta#"T"r"C"P"1 ubiquitin-ligase in the presence of E1 and E2 prior to proteasomal degradation. Here, we describe a novel inhibitor termed GS143, which suppressed I#kappa#B#alpha# ubiquitylation, but not I#kappa#B#alpha# ...

KoreaScience (Korea)

Full Text Available

UK PubMed Central (United Kingdom)

Chronic pain patients who show aberrant drug-related behavior often are discontinued from treatment when they are noncompliant with their use of opioids for pain. The purpose of this study was...Full Text Available

UK PubMed Central (United Kingdom)

Choice procedures have indicated that the relative reinforcing effectiveness of opioid drugs increases during opioid withdrawal. The demand curve, an absolute measure of reinforcer value, has not been...Full Text Available

CERN Document Server

We show, assuming the consistency of one measurable cardinal, that it is consistent for there to be exactly kappa+ many normal measures on the least measurable cardinal kappa. This answers a question of Stewart Baldwin. The methods generalize to higher cardinals, showing that the number of lambda strong compactness or lambda supercompactness measures on P_kappa(lambda) can be exactly lambda+, if lambda>kappa is a regular cardinal. We conclude with a list of open questions. Our proofs use a critical observation due to James Cummings.

Energy Technology Data Exchange (ETDEWEB)

Abstract Not Provided

UK PubMed Central (United Kingdom)

To study the effect of agonist on the TRH (thyrotrophin-releasing hormone) receptor protein, an epitope-tagged receptor was stably expressed in HEK-293 cells (human embryonic kidney 293 cells) and receptor...Full Text Available

Science.gov (United States)

... as far as mammary development is concerned but carries the NF-κB reporter, there is diffuse NF-κB activity throughout the epithelial tissue that is ...

Energy Technology Data Exchange (ETDEWEB)

In a given species, injected opioid peptides usually cause changes in temperature similar to those caused by nonpeptide opioids. The main effect in those species most studied, the cat, rat, and mouse, is an increase in the level about which body temperature is regulated; there is a coordinated change in the activity of thermoregulatory effectors such that hyperthermia is produced in both hot and cold environments. Larger doses may depress thermoregulation, thereby causing body temperature to decrease in the cold. Elicitation of different patterns of response over a range of environmental temperatures and studies with naloxone and naltrexone indicate that stimulation of a number of different receptors by both peptide and nonpeptide opioids can evoke thermoregulatory responses. ..beta..-Endorphin is readily antagonized by naloxone whereas methionine-enkephalin can act on naloxone-insensitive receptors. Moreover, synthetic ...

Energy Technology Data Exchange (ETDEWEB)

The Flory model is applied to predict the isobaric expansion coefficients, {alpha}{sub P}, isentropic, {kappa}{sub S}, and isothermal, {kappa}{sub T}, compressibilities and speeds of sound, u, of the highly complex mixtures: hydroxyether + alkane, + dibutylether, + 1-butanol or + 2-methoxyethanol, 1-alkanol + alkane, and 1-alkanol + dibutylether. Predictions were obtained using the energetic parameter, {chi}{sub 12}, determined from values of excess enthalpies, H{sup E}, and from values of the excess isochoric internal energies, U{sub V}{sup E}, at equimolar composition. No meaningful differences exist between such predictions. Deviations between experimental and calculated values are lower than 2% for mixtures containing alkoxyethanols. Poorer results are obtained for 1-alkanol + dibutylether mixtures with deviations up to 5%. It is shown that predictions on {alpha}{sub P}, {kappa}{sub S}, {kappa}{sub ...

UK PubMed Central (United Kingdom)

BackgroundWe have previously reported that low concentrations of cigarette smoke extract induce DNA damage without leading to apoptosis or necrosis in human bronchial epithelial...Full Text Available

Science.gov (United States)

We investigate the form factors of the chiral-odd nucleon matrix element of the tensor current. In particular, we aim at the anomalous tensor magnetic form factors of the nucleon within the framework of the SU(3) and SU(2) chiral quark-soliton model. We consider 1/N{sub c} rotational corrections and linear effects of SU(3) symmetry breaking with the symmetry-conserving quantization employed. We first obtain the results of the anomalous tensor magnetic moments for the up and down quarks: {kappa}{sub T}{sup u}=3.56 and {kappa}{sub T}{sup d}=1.83, respectively. The strange anomalous tensor magnetic moment is yielded to be {kappa}{sub T}{sup s}=0.2{approx}-0.2, that is compatible with zero. We also calculate the corresponding form factors {kappa}{sub T}{sup q}(Q{sup 2}) up to a momentum transfer Q{sup 2{<=}}1 GeV{sup 2} at a renormalization scale of 0.36 GeV{sup 2}.

Science.gov (United States)

A new method of administration of an opioid was recently registered: fentanyl transdermal (brand name: Durogesic), intended particularly for the indication range 'pain in cancer'. Fentanyl is lipid-soluble so that deposition in the skin takes place and the biological half-life is approximately 20 hours after removal of the plaster. It is safe to start on a basis of an equianalgesic conversion of 100:1 in relation to oral morphine, although this may entail some risk of fentanyl under dosage. The dose adjustment time is 12-24 hours before a constant fentanyl level is reached; therefore, after attaching the first sticking plaster, the original morphine dose should be continued for another 12 hours. In addition, the patient may, if necessary, be given supplementary morphine preferably as a short-acting drug. There seems to be no clear indication for transdermal fentanyl either in neuropathic pain or in chronic benign pain. PMID:9221362

UK PubMed Central (United Kingdom)

BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundPostoperative delirium is a topic of great importance in the geriatric surgical specialty. Although antipsychotic drugs are the medications most frequently used to treat...Full Text Available

UK PubMed Central (United Kingdom)

In laboratory studies, hamsters (Mesocricetus spp.) exhibit intense male-male aggression, thus making them an excellent model system for studies of the functional and mechanistic...Full Text Available

UK PubMed Central (United Kingdom)

The main function of white adipose tissue is to store nutrient energy in the form of triglycerides. The mechanism by which free fatty acids (FFA) move into and out of the adipocyte has not been resolved....Full Text Available

UK PubMed Central (United Kingdom)

BackgroundCancer stem cells (CSCs) have increased resistance to cancer chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs) by growth with chemotherapeutic drugs, and/or...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundCompared to outbred Sprague Dawley (SD) rats, inbred Brown Norway (BN) rats exhibit less prepulse inhibition of startle (PPI) at long prepulse intervals,...Full Text Available

UK PubMed Central (United Kingdom)

Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

Molar excess volumes, V{sup E}, molar excess enthalpies, H{sup E}, and speeds of sound, u, of o-toluidine (i) + cyclohexane or n-hexane or n-heptane (j) binary mixtures have been determined over entire range of composition at 308.15 K. Speeds of sound data have been utilized to predict isentropic compressibility changes of mixing, {kappa}{sub S}{sup E} of (i + j) mixtures. The observed V{sup E}, H{sup E} and {kappa}{sub S}{sup E} data have been analyzed in terms of Graph theory. The analysis of V{sup E} data by Graph theory reveals that o-toluidine exists as an associated molecular entity and (i + j) mixtures contain 1:1 molecular complex. It has been observed that V{sup E}, H{sup E} and {kappa}{sub S}{sup E} values calculated by Graph theory compare well with their corresponding experimental values. The observed data have also been analyzed in term of Flory theory.

Energy Technology Data Exchange (ETDEWEB)

The unit cost of energy production of wind generators is examined by means of a model of the turbine power curve and the Weibull model of wind probability function, by applying the usual economic equations. The analysis is carried out in terms of dimensionless variables whose range of variability is defined by examining the data of 80 modern commercial wind turbines; likewise, the economic parameters are based on the present state of costs. The unit cost decreases asymptotically when alpha (ratio between mean wind speed and cut-in speed) - increases and shows a lower limit of 2 to 5 Ecent/kWh. This cost depends both on the value of the machine parameter {phi} (ratio between nominal and cut-in speed) and on the basic prices. The effect of the Weibull shape parameter kappa is different according to the values of {alpha} and {phi}: with low {alpha} and high {phi} the unit cost increases along with {kappa} (that is with the regularity of the ...

Energy Technology Data Exchange (ETDEWEB)

The receptor occupancy-biological effect relationship for muscarinic receptors in guinea pig ileal smooth muscle has been studied by comparison of radioligand binding and contractile response. Muscarinic receptors in homogenates of ileal smooth muscle were labeled with (/sub 3/H)-1-Quinuclidinyl benzilate. Treatment with propylbenzilylcholine mustard (PrBCM), to inactivate irreversibly muscarinic receptors, caused a large dose dependent rightward shift of the dose-response curve to three agonistic furtrethonium derivatives with a concomitant decrease in maximal response. Using those data, the fraction of receptors remaining unoccupied (q-values) and true affinity constants (-log K/sub A/-values) were calculated. Exposure to 20 or 60 nM PrBCM for 15 minutes resulted in a 39% and a 61% reduction in specific (/sup 3/H)-1-Quinuclidinyl benzilate binding sites respectively to be compared with a 62% and a 85% decrease expected from calculated q-values. K/sub A/-values ...

UK PubMed Central (United Kingdom)

The activation of nuclear factor-kappa B1 (NFκB1) in cancer cells may confer resistance to ionizing radiation (IR). To enhance the therapeutic efficiency of IR in lung cancer, we screened for...Full Text Available

Science.gov (United States)

Several examples of agonist-directed trafficking of receptor signalling at 5-HT2A and 5-HT2C receptors have been reported that involve independent downstream transduction pathways. We now report the functional selectivity of a series of chemically diverse agonists at human (h)5-HT2A, h5-HT2B and h5-HT2C-VSV by examining two related responses, the upstream activation of Gq/11 proteins in comparison with its associated cascade of calcium mobilisation. At the h5-HT2A receptor, d-lysergic acid diethylamide (LSD) and the antiparkinsonian agents lisuride, bromocriptine and pergolide exhibit a higher potency for Gq/11 activation than calcium release in contrast with all the other tested ligands such as 5-HT, mCPP and BW723C86, that show an opposite preference of signalling pathway. Comparable observations are made at h5-HT2B and h5-HT2C-VSV receptors, suggesting a similar mechanism of functional selectivity for the three serotonin receptors. ...

British Library Electronic Table of Contents (United Kingdom)

Results in this study are consistent with those of Murdock and his colleagues who clearly demonstrated that clonidine, an agonist of octopaminergic receptors in some insects, significantly increases sucrose feeding. Their studies, however, did not examine the effect of clonidine on protein feeding. Injection of a 20mg/ml/fly dose of clonidine significantly reduces protein feeding in both sexes of Phormia regina, instead of stimulating feeding as is observed with carbohydrate feeding. The manner in which the flies are fed prior to starvation and the method of testing influences the amounts of diet consumed. It is proposed that the biogenic amines influence the state of hunger (i.e., protein versus carbohydrates) while other chemicals and neural mechanisms (i.e., such as sulfakinins and stre...

UK PubMed Central (United Kingdom)

Metabotropic glutamate receptor 2/3 (mGluR2/3) agonists were shown previously to nonselectively decrease both cocaine- and food-maintained responding in rats. mGluR2 positive allosteric modulators (PAMs)...Full Text Available

UK PubMed Central (United Kingdom)

Background2-Methylthioadenosine 5'-triphosphate (2-MeSATP), formerly regarded as a specific P2Y (metabotropic) purinergic receptor agonist, stimulates Ca²⁺ influx and...Full Text Available

UK PubMed Central (United Kingdom)

σ-Receptor (σR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of σR ligands in rats trained to self-administer...Full Text Available

UK PubMed Central (United Kingdom)

Oestrogen has been reported to modulate tumour necrosis factor (TNF), interleukin (IL)-1 and IL-6 cytokine levels in human mononuclear cell cultures. In the present study, the effects of exogenous oestrogen...Full Text Available

International Nuclear Information System (INIS)

Aim: There has been a great demand for developments of the radioligands to visualize the N-methyl-D-aspartate (NMDA) receptors by PET/SPECT. We have recently synthesized two C-11 labeled antagonists for the glycine-binding site on NMDA receptors. The aim of this work is to examine for their in vitro and in vivo binding characteristics, and to evaluate their potentials as PET radioligands for the NMDA receptors. Materials and methods: Two C-11 labeled 4-hydroxy-2-quinolones (1 and 2) were synthesized by conventional methylation of the corresponding phenols with ["1"1C]methyl iodide. In vitro and ex vivo quantitative autoradiographs with imaging plate, as well as animal PET, were employed in order to evaluate their in vitro and in vivo binding to the NMDA receptors. Results: The compound 1 showed the specific binding to rat brain slices with higher localization in the hippocampus and cerebral cortex than in the cerebellum. Both glycine antagonists and agonists ...

International Nuclear Information System (INIS)

Purpose: To determine the value of MRI in the preoperative evaluation of chronic paranasal sinusitis and to compare the results with CT and intraoperative findings. Method/Materials: 42 patients with clinical signs of chronic paranasal sinusitis underwent MRI after CT evaluation on one day, with subsequent functional endoscopic sinus surgery on the next day. Coronary CT was obtained with 5-mm slices and table-feed in the prone position, while MRI was performed in the supine position with coronary T_2-TSE+pd and coronary and transverse HASTE, each with 5-mm slice thickness. Aquisition time in MRI was less than 8 minutes. Two radiologists reviewed the CT and MRI scans for signs of sinusitis and detection of anatomical landmarks. The results were correlated with the intraoperative findings. Results: MRI offered no artifacts of dental work and showed more often high quality pictures than CT. CT and MRI demonstrated a good correlation in the detection of mucosal pathologies ...

CERN Document Server

We investigate the effect of anomalous gamma-W-W couplings in e-gamma --> nu W through the angular and energy spectrum of the secondary leptons. Within the narrow-width approximation, a semi-analytical study of the secondary lepton energy-angle double distribution is considered. Utility of observables derived from this is demonstrated by considering the anomalous coupling, delta-kappa-gamma. Results of our investigation for typical ILC machine considered at Ecm = 300-1000 GeV re-affirms potential of this collider as a precision machine.

DEFF Research Database (Denmark)

Applicability of a model to estimate radiofrequency electromagnetic field (RF-EMF) strength in households from mobile phone base stations was evaluated with technical data of mobile phone base stations available from the German Net Agency, and dosimetric measurements, performed in an epidemiological study. Estimated exposure and exposure measured with dosemeters in 1322 participating households were compared. For that purpose, the upper 10th percentiles of both outcomes were defined as the 'higher exposed' groups. To assess the agreement of the defined 'higher' exposed groups, kappa coefficient, sensitivity and specificity were calculated. The present results show only a weak agreement of calculations and measurements (kappa values between -0.03 and 0.28, sensitivity between 7.1 and 34.6). Only in some of the sub-analyses, a higher agreement was found, e.g. when measured instead of interpolated geo-coordinates were used to calculate the ...

British Library Electronic Table of Contents (United Kingdom)

The aim of this study was to measure the nociceptive response (avoidance latency) of the land snail Megalobulimus abbreviatus (N=8 in each group) after topical capsaicin exposure (0.1% and 0.5% in 20% ethanol) and to compare it to a well-studied stressful (50??C) thermal stimulus model. We also tested if ruthenium red, and capsazepine, respectively nonselective and selective TRPV1 receptor antagonists, could modify both capsaicin- and thermal-evoked responses. Finally, animals were pretreated with morphine, naloxone or morphine plus naloxone prior to capsaicin stimuli. Latencies were measured when the animal lifted its head?foot complex 1?cm from the substrate. Data were compared using ANOVA and LSD post hoc, and the Student T Test (pM. abbreviatus.

British Library Electronic Table of Contents (United Kingdom)

Downregulation of anterior pituitary GnRH-receptors by application of a slow release GnRH-implant offers an effective and reversible alternative to surgical castration of the male dog. Aim of the present study was to test the efficacy and the underlying mechanisms of a new non-biodegradable controlled-release device implant (Gonazon, Intervet, containing 18.5mg of the GnRH-agonist Azagly-Nafarelin). Eight male beagle dogs were implanted s.c. at the para-umbilical region. In four dogs implant removal was after 180 days (group 1), in the other four dogs after 365 days (group 2). Eleven weeks after implantation availability of LH was reduced (p<0.0001) by 70%. After an initial increase lasting for about 4 days, testosterone (T) and estradiol (E2) concentrations decreased (p<0.0001) to basal l...

Science.gov (United States)

The role of intracellular Ca2+ (Ca2+i) on hematopoiesis was investigated in long term bone marrow cultures using cytokines and agonists of P2 receptors. Cytokines interleukin 3 and granulocyte/macrophage colony stimulator factor promoted a modest increase in Ca2+i concentration ([Ca2+]i) with activation of phospholipase Cgamma, MEK1/2, and Ca2+/calmodulin kinase II. Involvement of protein kinase C was restricted to stimulation with interleukin 3. In addition, these cytokines promoted proliferation (20 times) and an increase in the Gr-1(-)Mac-1+ population with participation of gap junctions (GJ). Nevertheless ATP, ADP, and UTP promoted a large increase in [Ca2+]i, moderate proliferation (6 times), a reduction in the primitive Gr-1(-)Mac-1(-)c-Kit+ population, and differentiation into macrophages without participation of GJ. It is likely that Ca2+i participates as a regulator of hematopoietic signaling: moderate increases in [Ca2+]i would be related to ...

Science.gov (United States)

The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms underlying the prosocial effects of nicotine and ethanol, we focused on social play behavior, the most characteristic social activity in adolescent rats. Social play behavior is rewarding, and it is modulated through opioid, cannabinoid and dopaminergic neurotransmission, which are also involved in the reinforcing properties of nicotine and ethanol. We found that nicotine and ethanol increased social play, without affecting locomotion or social exploration. Their effects depended on the level of social activity of the partner, and were comparable in familiar and unfamiliar environments. At doses that increased social play, nicotine and ethanol had no anxiolytic effects in the elevated plus-maze. By contrast, the prototypical anxiolytic drug diazepam reduced social play at ...

British Library Electronic Table of Contents (United Kingdom)

Purpose To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Methods Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular KATP (PNU-37883A) or BKCa [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-?B) was assessed by electrophoretic mobility shift as...

British Library Electronic Table of Contents (United Kingdom)

Background Experimental and clinical studies have identified a crucial role of microcirculation impairment in severe infections. We hypothesized that mottling, a sign of microcirculation alterations, was correlated to survival during septic shock. Methods We conducted a prospective observational study in a tertiary teaching hospital. All consecutive patients with septic shock were included during a 7-month period. After initial resuscitation, we recorded hemodynamic parameters and analyzed their predictive value on mortality. The mottling score (from 0 to 5), based on mottling area extension from the knees to the periphery, was very reproducible, with an excellent agreement between independent observers [kappa?=?0.87, 95% CI (0.72?0.97)]. Results Sixty patients were included. The SOFA scor...

Energy Technology Data Exchange (ETDEWEB)

Purpose: To determine the value of MRI in the preoperative evaluation of chronic paranasal sinusitis and to compare the results with CT and intraoperative findings. Method/Materials: 42 patients with clinical signs of chronic paranasal sinusitis underwent MRI after CT evaluation on one day, with subsequent functional endoscopic sinus surgery on the next day. Coronary CT was obtained with 5-mm slices and table-feed in the prone position, while MRI was performed in the supine position with coronary T{sub 2}-TSE+pd and coronary and transverse HASTE, each with 5-mm slice thickness. Aquisition time in MRI was less than 8 minutes. Two radiologists reviewed the CT and MRI scans for signs of sinusitis and detection of anatomical landmarks. The results were correlated with the intraoperative findings. Results: MRI offered no artifacts of dental work and showed more often high quality pictures than CT. CT and MRI demonstrated a good correlation in the detection of mucosal pathologies ...

Energy Technology Data Exchange (ETDEWEB)

A static plasma grating has been demonstrated experimentally in a large optical cavity FIB-DBR GaAlAs/GaAs laser diode. The grating is formed by implanting stripes of dopants with a focused ion beam (FIB). The dopants ionize to form periodic fluctuations in the carrier concentration which, through the Kramers-Kronig relations, form an index grating. A model of the grating strength for optimization of the laser design is developed and presented here. The computed results show that /kappa/ can be increased by more than an order of magnitude over the 15 cm/sup -1/ experimentally. Therefore, FIB-DBR (or -DFB) lasers with performance comparable to that of conventional DBR (or DFB) lasers can be expected.

British Library Electronic Table of Contents (United Kingdom)

A phenomenon based model for chlorine dioxide delignification of chemical pulp is introduced. The pulp suspension environment is modeled using the concept of two liquid phases, one inside and the other external to the fiber wall. Physico-chemical processes taking place during delignification are implemented with thermodynamic, mass transfer and reaction kinetic models. A broad library of chemical reactions is introduced. Inclusion of each reaction is justified. The model response is tested against experimental laboratory delignification results (o-delignified birch pulp). The experimental data consists of kappa number, hexenuronic acid, inorganic oxy-chlorine compound, and organochlorine (AOX, OX) measurements at several time points during five delignification experiments. The model predic...

Energy Technology Data Exchange (ETDEWEB)

This document deals with the couplings between the W boson and Z and gamma particles. WWZ and WW{gamma} vertex are predicted by the electroweak theory based on the symmetry group SU(2){sub L}*U(1){sub Y}, their existence is confirmed by the measurement of the production cross-section of W pairs at LEP. The effective values of the couplings are modified by the introduction of standard model particle loops at the vertex level, the impact on the coupling value is assessed to reach 10{sup -3}. These loops can also include beyond-the-standard-model particles, their impact is in the magnitude order of 10{sup -3} for most models. The fully description of these loops requires the values of 14 complex parameters whose measurement will give information about the existence of new particles. Nevertheless the number of events at LEP is not sufficient to measure all the parameters simultaneously. As a consequence the analysis is limited to the 3 most promising parameters: g{sub 1}{sup Z}, ...

Energy Technology Data Exchange (ETDEWEB)

The finite-volume based commercial CFD-code Fluent was used to simulate the reacting flow in a heavy fuel oil fired laboratory furnace. Both the standard {kappa}-{epsilon} turbulence model and the Reynolds stress model (RSM) were tested. The combustion model was based on the conserved scalar (mixture fraction) and prescribed probability density function approach. The heavy fuel oil droplet trajectories were predicted by solving the momentum equations for the droplets using the Lagrangian treatment. The soot distribution in the furnace was calculated by solving a transport equation for the soot mass fraction. Simple expressions for the soot formation and oxidation rates were employed. The radiation heat transfer equation was solved using the finite volume method. The formation of thermal NO from molecular nitrogen was modeled according to the extended Zeldovich mechanism. Fuel-based NO was modeled assuming that all the nitrogen in the fuel is released as hydrogen ...

British Library Electronic Table of Contents (United Kingdom)

Several old and new observations suggest the existence in Crohn's disease of a phagocytic disorder of macrophages related to impaired bactericidal activity of host cells or to the presence of invasive bacteria that have developed strategies to counteract macrophage killing. It was recently reported that disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease. Secretion of proinflammatory cytokines by CD macrophages was impaired in response to E. coli or specific Toll-like receptor agonists. In addition, major advances in the etiology of Crohn's disease came from the existence of polymorphism in NOD2 and autophagy-related susceptibility genes (ATG16L1 and IRGM) in patients and from the identification of the presence of adhere...

Energy Technology Data Exchange (ETDEWEB)

..cap alpha..-2 adrenergic agents have been shown to influence blood pressure, heart rate and other physiological and behavioral functions through interactions with adrenergic pathways within the central nervous system. Pharmacologically relevant ..cap alpha..-1 adrenergic receptors were biochemically characterized and radiohistochemically analyzed in intact tissue sections of the rat and human central nervous system. The anatomical distribution of the ..cap alpha..-2 receptors, labeled with the agonist (/sup 3/H)para-aminoclonidine, verified the concept that ..cap alpha..-2 receptors are closely associated with adrenergic nerve terminals and that ..cap alpha..-2 agents can influence autonomic and endocrine function through an action in the central nervous system. Since ..cap alpha..-2 agonists can influence sympathetic outflow, ..cap alpha..-2 binding sites were closely analyzed in the intermediolateral cell column of the thoracic spinal cord. ...

Energy Technology Data Exchange (ETDEWEB)

(-)-N6-(R-4-Hydroxyphenylisopropyl)adenosine (HPIA) was iodinated with NaI and trace /sup 125/I. Mono- and diiodinated reaction products and the starting material were separated by high pressure liquid chromatography and the structures of the reaction products were verified by NMR. (-)-N6-(R-Phenylisopropyl)adenosine (PIA), IHPIA, and I2HPIA decreased rat atrial contractility with ED50 values of 24, 28, and 33 nM, respectively. The contractile effects of these compounds were competitively blocked by theophylline (KI . 7.9 microM), but were not affected by adenosine deaminase. IHPIA also inhibited (-)isoproterenol-stimulated cyclic AMP accumulation in adipocytes with an ED50 (10 nM) and to an extent (83%) nearly identical to PIA. (/sup 125/I)HPIA prepared using carrier-free /sup 125/I bound to adenosine receptors on membranes from rat cerebral cortex, adipocyte ghosts, and heart ventricles. Binding was inhibited stereospecifically by PIA and by other adenosine analogues and ...

DEFF Research Database (Denmark)

Background:The validity of dementia diagnoses in the Danish nationwide hospital registers was evaluated to determine the value of these registers in epidemiological research about dementia. Methods: Two hundred patients were randomly selected from 4,682 patients registered for the first time with a dementia diagnosis in the last 6 months of 2003. The patients' medical journals were reviewed to evaluate if they fulfilled ICD-10 and/or DSM-IV criteria for dementia and specific dementia subtypes. The patients who were still alive in 2006 were invited to an interview. Results: One hundred and ninety-seven journals were available for review and 51 patients were interviewed. A registered diagnosis of dementia was found to be correct in 169 (85.8%) cases. Regarding dementia subtypes, the degree of agreement between the registers and the results of the validating process was low with a kappa of 0.36 (95% CI 0.24-0.48). Conclusion: The validity of dementia syndrome in the ...

Energy Technology Data Exchange (ETDEWEB)

The design of the KSTAR (Korea Superconducting Tokamak Advanced Research) tokamak (R{sub 0} = 1.8 m, a= 0.5 m, {kappa} = 2, {delta} = 1.8 B{sub T} = 3.5 T, I{sub p} 2 MA, {tau}{sub pulse} = 300 s) is being undertaken to do long-pulse. high {beta}, advanced tokamak operating-mode fusion physics experiments. The ion cyclotron (IC) system will deliver 6 MW of rf power to the plasma in the 25 - 60 MHz frequency range, using a single four-strap antenna mounted in a midplane port. It will be used for ion heating, fast-wave current drive (FWCD), and mode conversion current drive (MCCD). The phasing between current straps in the antenna will be adjustable quickly during operation to provide the capability of changing the current-drive efficiency. The IC system will be capable of 300 s operation with 12 MW (upgrade) of rf power to the plasma. (author)

International Nuclear Information System (INIS)

The authors used radioligand binding and studies of cell contraction to characterize muscarinic receptors on dispersed smooth muscle cells from rabbit proximal and distal colon. Cells obtained after serial incubations in collagenase were used to measure binding of tritiated quinuclidinyl benzilate (["3H]QNB). At 37 degree C, specific ["3H]QNB binding was saturable and linearly related to cell number. Nonlinear regression analysis was used to determine the affinity of ["3H]QNB for its receptor. The IC_5_0 for the muscarinic agonists bethanechol and oxotremorine were 80 and 0.57 #mu#M, respectively. Hill coefficients were 0.67 for both, suggesting more complex interaction involving receptors of different affinities. In studies of cell contraction, bethanechol stimulated a dose-dependent decrease in cell length with half the maximal contraction occurring at 100 pM. These results suggest that (1) contraction is mediated by binding of bethanechol to M_2-muscarinic ...

Energy Technology Data Exchange (ETDEWEB)

The effects of muscarinic agonists and diisopropylfluorophosphate (DFP) on muscarinic receptor density and muscarinic receptor-mediated responses was assessed in mouse brain and mouse neuroblastoma cells (clone N1E-115). Utilizing the antagonist ({sup 3}H)quinuclidinyl benzilate (({sup 3}H)QNB), there was no difference in the maximal binding capacity (B{sub max}) or equilibrium dissociation constant (K{sub d}) between untreated and 24 hour DFP-treated mice. However, one administration of DFP produced a 24% and 33% decrease in B{sub max} measured by ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) after 18 and 24 hours which was rapidly reversible within 36 hours after DFP treatment. The loss of ({sup 3}H)NMS binding sites following acute DFP treatment was not accompanied by a change in a particular muscarinic receptor binding conformation. Furthermore, the magnitude of muscarinic receptor-mediated phosphoinositide hydrolysis was unchanged following short-term DFP ...

Energy Technology Data Exchange (ETDEWEB)

Targeted studies completed include the evaluation of tritiated N-0437, evaluation of /sup 35/S-cysteamine, evaluation of /sup 18/F-FDG and initiation of synthetic efforts towards the synthesis of iodinated N-0437 and pergolide analogs. The direction of the project has been changed due to several factors which include the decided lack of favorable experimental results, the excellence of results using muscarinic receptor ligands in pituitary, brain and heart and the contention of the DOE review panel that the original grant proposal was based on flawed assumptions together with their perceived lack of importance to pituitary imaging. In the final year of this grant, three studies will be completed. The first study is the continuation of synthetic efforts to prepare iodinated N-0437 and pergolide analogs for possible use as brain imaging agents. The second study is directed towards completion of biochemical evaluation of various muscarinic receptor analogs for heart, brain and (possible) ...

International Nuclear Information System (INIS)

The thiazolidinedione (TZD) or glitazone class of peroxisome proliferator-activated-#gamma# (PPAR-#gamma#) ligands not only induce adipocyte differentiation and increase insulin sensitivity, but also exert growth inhibitory effects on several carcinoma cell lines in vitro as well as in vivo. In the current study the in vitro effect of four PPAR-#gamma# agonists (ciglitazone, pioglitazone, troglitazone, rosiglitazone) on the cell growth of seven human neuroblastoma cell lines (Kelly, LAN-1, LAN-5, LS, IMR-32, SK-N-SH, SH-SY5Y) was investigated. Growth rates were assessed by a colorimetric XTT-based assay kit. Expression of PPAR-#gamma# protein was examined by immunohistochemistry and Western blot analysis. All glitazones inhibited in vitro growth and viability of the human neuroblastoma cell lines in a dose-dependent manner showing considerable effects only at high concentrations (10 #mu#M and 100 #mu#M). Effectiveness of the glitazones on neuroblastoma cell growth ...

British Library Electronic Table of Contents (United Kingdom)

Atrial natriuretic peptide (ANP) causes relaxation in the opossum lower esophageal sphincter. The effects of dendroaspis natriuretic peptide (DNP) and other natriuretic peptides in the lower esophageal sphincter were not known. We measured the relaxation of transverse strips from the guinea pig lower esophageal sphincter caused by DNP, ANP, brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and a natriuretic peptide receptor-C agonist des[Gln^1^8, Ser^1^9, Gly^2^0, Leu^2^1, Gly^2^2]ANP(4-23) amide (cANF(4-23)) in vitro. In resting strips of the guinea pig lower esophageal sphincter DNP and BNP caused marked relaxations. Furthermore, in both sarafotoxin S6c and carbachol-contracted lower esophageal sphincter strips, DNP caused marked and BNP caused moderate, concentration-de...

Science.gov (United States)

A hypotheses that mitoxantrone is a competitive antagonist at muscarinic cholinergic receptors was examined in guinea-pig hearts. In isolated left atrial muscle preparations, electrically paced at 2 Hz, the muscarinic agonist, carbachol, caused a concentration-dependent decrease in developed tension. Mitoxantrone caused a parallel right-ward shift of the concentration-response curve for carbachol. Schild plots for the effect of mitoxantrone on the carbachol concentration-response relationship were linear with a slope of 0.88 which was not significantly different from the unity. The right-ward shift of the carbachol concentration-response relationship by mitoxantrone significantly reversed after an additional incubation with a mitoxantrone-free solution, although the reversal was incomplete after a 2-h incubation in the mitoxantrone-free solution. Mitoxantrone caused a concentration-dependent displacement of specific [3H]quinuclidinyl benzilate binding to membrane ...

Energy Technology Data Exchange (ETDEWEB)

The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulating cell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact inhibition. It is now generally accepted that progenitor cells exist in the liver, are activated in various liver diseases and can form a potential target cell population for both tumor ...

Scientific Electronic Library Online (English)

Abstract in english The aim of the present study was to assess the analgesic activity of the aerial parts of two Hypericum species native to Southern Brazil, H. caprifoliatum and H. polyanthemum. The antinociceptive effect of the H. polyanthemum cyclohexane extract (POL; 180 mg/kg) and of the H. caprifoliatum methanol (MET) and cyclohexane (CH) extracts (90 mg/kg) was evaluated in the hot-plate (ip and po) and writhing (po) tests using male Swiss CF1 mice weighing 22-27 g (N = 10 per group). (more) All extracts displayed antinociceptive effects in the hot-plate test (MET ip = 48%, MET po = 39%, CH ip = 27%, CH po = 50%, POL ip = 74%, and POL po = 49% compared to control). Pretreatment with naloxone (2.5 mg/kg, sc) abolished the effects of CH and POL, and partially prevented the analgesia induced by MET administered by the ip (but not by the po) route. POL and CH (po) significantly reduced the number of writhes induced by acetic acid, while MET was ineffective in this regard. We ...

International Nuclear Information System (INIS)

Apparent molar volumes of aqueous methyldiethanolamine and its salt were determined with platinum vibrating tube densitometers over a range of temperatures from 283K=kappa#_T"o. The standard partial molar volumes V"o for the neutral amine and its salt show increasingly positive and negative values, respectively, at high temperatures and pressures, as predicted by corresponding states and group ...

Science.gov (United States)

We present a high-statistics calculation of nucleon electromagnetic form factors in N{sub f}=2+1 lattice QCD using domain wall quarks on fine lattices, to attain a new level of precision in systematic and statistical errors. Our calculations use 32{sup 3}x64 lattices with lattice spacing a=0.084 fm for pion masses of 297, 355, and 403 MeV, and we perform an overdetermined analysis using on the order of 3600 to 7000 measurements to calculate nucleon electric and magnetic form factors up to Q{sup 2{approx_equal}}1.05 GeV{sup 2}. Results are shown to be consistent with those obtained using valence domain wall quarks with improved staggered sea quarks, and using coarse domain wall lattices. We determine the isovector Dirac radius r{sub 1}{sup v}, Pauli radius r{sub 2}{sup v} and anomalous magnetic moment {kappa}{sub v}. We also determine connected contributions to the corresponding isoscalar observables. We extrapolate these observables to the physical pion mass using ...

Science.gov (United States)

Anthraquinones are widely present in plant kingdom, and clinically used as laxatives. Environmental contaminants, dioxins, develop various adverse effects through transformation of a cytosolic aryl hydrocarbon receptor (AhR). We investigated the effects of 18 anthraquinones and 7 of their structurally related compounds on transformation of the AhR estimated by its DNA-binding activity in the cell-free system. 1,4-Dihydroxyanthraquinone (quinizarin), 1,5-dihydroxyanthraquinone (anthrarufin), 1,8-dihydroxyanthraquinone (danthron), and 5-hydroxy-1,4-naphthoquinone (juglone) strongly suppressed DNA-binding activity of the AhR induced by 0.1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with their IC(50) values around 1 muM. On the other hand, anthraquinone, 2,6-dihydroxyanthraquinone (anthraflavic acid), and 2-hydroxy-1,4-naphthalendione (lawsone) showed moderate effects. Quantitative structure-activity relationships analysis demonstrated that hydroxyl groups at C1 or C4 but not C3 ...

International Nuclear Information System (INIS)

Full text: The maturation of chicken forebrain is protracted and occurs well after synapse formation providing a good model for studying mechanisms of brain maturation. Using microslices from immature (10 day) and adult chicken forebrain prepared after decapitation, we have examined functional properties of NMDA and AMPA receptors by measuring agonist-induced uptake of "4"5Ca"2"+ . The rate and extent of NMDA induced "4"5Ca"2"+ accumulation decreased during maturation with no change in EC_5_0. The rate and extent of the AMPA induced response also decreased with a 60-fold increase in EC_5_0. However, the total NMDA receptor content did not change as indicated by 3 H-MK801 binding and NR1 immunoreactivity in P2 fractions. Similarly, there was no change in the B_m_a_x of "3H-AMPA, though there was a two-fold increase in K_D, and little or no change in the immunoreactivity in GluR1, 2, 2/3 or 4. These results suggest that it is the regulation of receptors, their ...

International Nuclear Information System (INIS)

The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the type of adrenergic receptor (AR) involved in the production of the major metabolite of this fatty acid. ["1"4C]AA was incubated with GPT-rings and the radiolabelled products were extracted and separated by TLC method. The medium was also assayed for radiolabelled immunoreactive PG's (iPG's) and leukotrienes (LT) B4 and C4 by RIA or Enzyme immunoassay (EIA) after exposure to various AR agonists. ["1"4C]AA was incorporated into GPT-rings and metabolized mainly into iPGE2 and smaller amounts into PGF2#alpha#. Trace amounts of PGD2 and 6-keto-PGF1#alpha# but not LTB4 or LTC4 were detected by RIA and/or EIA. Incubation of GPT rings for 15 minutes with isoproterenol and salbutamol resulted in a significant increase of PGE2 synthesis (optimum conc: 10"-"7, 10"-"7M respectively). In contrast, dobutamine, norepinephrine, phenylnephrine and xylazine (up to 10"-"6M) did not ...

International Nuclear Information System (INIS)

Thromboxane A2, the predominant product of arachidonic acid metabolism in the blood platelet, is a potent vasoconstrictor and platelet agonist. During its biosynthesis from cyclic endoperoxide, 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) is formed in equal amounts. The further metabolism of HHT, catalyzed by 15-hydroxyprostaglandin dehydrogenase, leads to 12-oxo-5Z,8E,10E-heptadecatrienoic acid (Oxo-HT). Sample workup procedures are described which allow for the sensitive and reproducible determination of these two arachidonic acid metabolites in human plasma by gas chromatography-mass spectrometry in the presence of deuterated analogues as internal standards. HHT is derivatized to the pentafluorobenzyl ester tert-butyldimethylsilyl ether. In order to enable quantification of low concentrations of about 10 pg/ml in nonstimulated human plasma, the samples have to be purified by HPLC. Oxo-HT is derivatized to the pentafluorobenzyl ester, which is purified by ...

Energy Technology Data Exchange (ETDEWEB)

Exogenous adenosine 5{prime}-triphosphate (ATP) mobilized intracellular calcium in human carcinoma A43l cells and in Swiss 3T3 and 3T6 mouse fibroblasts by increasing inositol trisphosphate similar to well down growth factors (platelet-derived growth factor (PDGF), epidermal growth factor (EGF), bradykinin (BK), serum). Calcium mobilization was examined by video imaging of fura-2 fluorescence is single cells, following the radioactive isotope {sup 45}Ca, and monitoring the decrease in fluorescence of cells loaded with chlortetracycline. Uridine 5{prime}-triphosphate, but not other nucleotides, mimicked ATP. Single-cell analysis revealed synchronous responses in 10 sec to ATP, BK or serum, while PDGF (3T3) and EGF (A431) produced slower signals with significant cell-to-cell variation. PDGF desensitized 3T3 cells to ATP and BK added 100 sec later but ATP or BK did not desensitized to PDGF. Homologous desensitization was seen with all agonists. Heterologous ...

International Nuclear Information System (INIS)

Serotonin is one of the neurotransmitters found in the brain and mediates brain functions. It is very well known that serotonin related brain abnormalities are exerted mainly via serotonin receptors in a similar manner to other neurotransmitters found in the brain. Recently, it has also been found that serotonin is involved in Alzheimer's disease either directly or indirectly by its actions on serotonergic neurons. To understand and treat the diseases caused by abnormalities in the serotonergic system in the brain, it is certain that its mechanism of function has to be well investigated. So far several 5-HT receptors and receptor subtypes have been well characterized. Moreover, serotonin agonists and antagonists acting on specific receptors are chemically synthesized and are now available for the prevention or treatment of serotonergic related diseases. In recent years, a great demand for developing neuroimaging agents has emerged for the diagnosis of abnormal ...