bluuebunny/crossref_metadata_2025 huggingface dataset:
Biventricular pacing-induced acute response in baroreflex sensitivity has predictive value for midterm response to cardiac resynchronization therapy
Authors: Gademan Maaike G. J. , van Bommel Rutger J. , Borleffs C. Jan Willem , Man SumChe , Haest Joris C. W. , Schalij Martin J. , van der Wall Ernst E. , Bax Jeroen J. , Swenne Cees A.
Published: April 2009

In a previous study we demonstrated that the institution of biventricular pacing in chronic heart failure (CHF) acutely facilitates the arterial baroreflex. The arterial baroreflex has important prognostic value in CHF. We hypothesized that the acute response in baroreflex sensitivity (BRS) after the institution of cardiac resynchronization therapy (CRT) has predictive value for midterm response. One day after implantation of a CRT device in 33 CHF patients (27 male/6 female; age, 66.5 ± 9.5 yr; left ventricular ejection fraction, 28 ± 7%) we measured noninvasive BRS and heart rate variability (HRV) in two conditions: CRT device switched on and switched off (on/off order randomized). Echocardiography was performed before implantation (baseline) and 6 mo after implantation (follow-up). CRT responders were defined as patients in whom left ventricular end-systolic volume at follow-up had decreased by ≥15%. Responders (69.7%) and nonresponders (30.3%) had similar baseline characteristics. In responders, CRT increased BRS by 30% ( P = 0.03); this differed significantly ( P = 0.02) from the average BRS change (−2%) in the nonresponders. CRT also increased HRV by 30% in responders ( P = 0.02), but there was no significant difference found compared with the increase in HRV (8%) in the nonresponders. Receiver-operating characteristic curve analysis revealed that the percent BRS increase had predictive value for the discrimination of responders and nonresponders (area under the curve, 0.69; 95% confidence interval, 0.51–0.87; maximal accuracy, 0.70). Our study demonstrates that a CRT-induced acute BRS increase has predictive value for the echocardiographic response to CRT. This finding suggests that the autonomic nervous system is actively involved in CRT-related reverse remodeling.
Cardiovascular responses to microinjections of urocortins into the NTS: role of inotropic glutamate receptors
Authors: Nakamura Takeshi , Sapru Hreday N.
Published: April 2009

Urocortin 1 (Ucn1) and urocortin 3 (Ucn3) are new members of the corticotrophin-releasing factor (CRF) peptide family. Ucn1 is a ligand for both the CRF type 1 receptors (CRF1Rs) and the CRF type 2 receptors (CRF2Rs), whereas Ucn3 is a high-affinity ligand for the CRF2Rs. Recently, we reported that Ucn3 microinjections into the medial nucleus tractus solitarius (mNTS) elicit decreases in mean arterial pressure (MAP) and heart rate (HR) (Nakamura T, Kawabe K, Sapru HN. Am J Physiol Heart Circ Physiol 296: H325–H332, 2009). The presence of CRF2Rs on afferent terminals has been reported in the mNTS of the rat. It was hypothesized that activation of CRF2Rs on afferent terminals in the mNTS may release glutamate, which, in turn, may elicit decreases in MAP and HR via activation of ionotropic glutamate receptors (iGLURs). This hypothesis was tested in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (100 nl) of Ucn1 (0.12 mM) into the mNTS elicited decreases in MAP and HR. The responses were partially blocked by microinjections of iGLUR antagonists into the mNTS. On the other hand, the decreases in MAP and HR elicited by microinjections of Ucn3 (0.06 mM) into the mNTS were completely blocked by microinjections of iGLUR antagonists into the mNTS. These results indicate that activation of CRF2Rs in the mNTS, by Ucn1 and Ucn3, releases glutamate, which, in turn, elicits decreases in MAP and HR via activation of iGLURs.
Determination of rate constants for turnover of myosin isoforms in rat myocardium: implications for in vivo contractile kinetics
Authors: Locher Matthew R. , Razumova Maria V. , Stelzer Julian E. , Norman Holly S. , Patel Jitandrakumar R. , Moss Richard L.
Published: April 2009

The ventricles of small mammals express mostly α-myosin heavy chain (α-MHC), a fast isoform, whereas the ventricles of large mammals, including humans, express ∼10% α-MHC on a predominately β-MHC (slow isoform) background. In failing human ventricles, the amount of α-MHC is dramatically reduced, leading to the hypothesis that even small amounts of α-MHC on a predominately β-MHC background confer significantly higher rates of force development in healthy ventricles. To test this hypothesis, it is necessary to determine the fundamental rate constants of cross-bridge attachment ( fapp) and detachment ( gapp) for myosins composed of 100% α-MHC or β-MHC, which can then be used to calculate twitch time courses for muscles expressing variable ratios of MHC isoforms. In the present study, rat skinned trabeculae expressing either 100% α-MHC or 100% β-MHC were used to measure ATPase activity, isometric force, and the rate constant of force redevelopment ( ktr) in solutions of varying Ca2+concentrations. The rate of ATP utilization was ∼2.5-fold higher in preparations expressing 100% α-MHC compared with those expressing only β-MHC, whereas ktrwas 2-fold faster in the α-MHC myocardium. From these variables, we calculated fappto be approximately threefold higher for α-MHC than β-MHC and gappto be twofold higher in α-MHC. Mathematical modeling of isometric twitches predicted that small increases in α-MHC significantly increased the rate of force development. These results suggest that low-level expression of α-MHC has significant effects on contraction kinetics.
Nonmyofilament-associated troponin T fragments induce apoptosis
Authors: Jeong Euy-Myong , Wang Xin , Xu Kun , Hossain M. Moazzem , Jin J.-P.
Published: April 2009

Troponin T (TnT) is a striated muscle-specific protein and an abundant component of the myofilaments. Nonmyofilament-associated TnT is rapidly degraded in myocytes, implying an importance in the maintenance of the cellular environment. However, if the level of nonmyofilament-associated TnT or TnT fragments exceeds the degradation capacity, it may cause cytotoxicity. To investigate this hypothesis, we constructed bicistronic vectors to express different portions of TnT polypeptide chain, together with nonfusion green fluorescent protein as a tracer for the transfection. Cytotoxicity of the TnT fragments was studied through forced expression in C2C12myoblasts and human embryonic kidney-293 nonmuscle cells and examination of the viability of the transfected cells. The results demonstrated that, in the absence of myofilaments, the conserved COOH-terminal and middle fragments of TnT were highly effective on inducing cell death via apoptosis, whereas the NH2-terminal variable region was not. As combined effects, nonmyofilament-associated intact cardiac TnT and a COOH-terminal truncated slow TnT fragment found in Amish nemaline myopathy exhibited intermediate cytotoxicity. A particular significance of this finding is that peak releases of TnT or TnT fragments from decomposition of a large number of myofibrils in acute myocardial infarction may breach the cellular protection of proteolytic degradation and result in apoptosis as a potential cause for the loss of cardiomyocytes.
Soluble adenylyl cyclase-dependent microtubule disassembly reveals a novel mechanism of endothelial cell retraction
Authors: Prasain Nutan , Alexeyev Mikhail , Balczon Ron , Stevens Troy
Published: April 2009

Soluble adenylyl cyclase toxins, such as Pseudomonas aeruginosa exoY, generate a cAMP pool that retracts cell borders. However, the cytoskeletal basis by which this cAMP signal retracts cell borders is not known. We sought to determine whether activation of chimeric, soluble adenylyl cyclase I/II (sACI/II) reorganizes either microtubules or peripheral actin. Endothelial cells were stably transfected with either green fluorescent protein-labeled α-tubulin or β-actin, and then infected with adenovirus to express sACI/II. Forskolin, which stimulates both the endogenously expressed transmembrane adenylyl cyclases and sACI/II, induced cell retraction accompanied by the reorganization of peripheral microtubules. However, cortical filamentous-actin (f-actin) did not reorganize into stress fibers, and myosin light-chain-20 phosphorylation was decreased. Isoproterenol, which activates endogenous adenylyl cyclases but does not activate sACI/II, did not induce endothelial cell gaps and did not influence microtubule or f-actin architecture. Thus, sACI/II generates a cAMP signal that reorganizes microtubules and induces cell retraction, without inducing f-actin stress fibers. These findings illustrate that endothelial cell gap formation can proceed without f-actin stress fiber formation, and provide mechanistic insight how bacterial adenylyl cyclase toxins reorganize the cytoskeleton to induce cell rounding.
Intranasal organic dust exposure-induced airway adaptation response marked by persistent lung inflammation and pathology in mice
Authors: Poole Jill A. , Wyatt Todd A. , Oldenburg Peter J. , Elliott Margaret K. , West William W. , Sisson Joseph H. , Von Essen Susanna G. , Romberger Debra J.
Published: April 2009

Organic dust exposure in agricultural environments results in an inflammatory response that attenuates over time, but repetitive exposures can result in chronic respiratory disease. Animal models to study these mechanisms are limited. This study investigated the effects of single vs. repetitive dust-induced airway inflammation in mice by intranasal exposure method. Mice were exposed to swine facility dust extract (DE) or saline once and once daily for 1 and 2 wk. Dust exposure resulted in increased bronchoalveolar lavage fluid neutrophils and macrophages after single and repetitive exposures. Lavage fluid TNFα, IL-6, keratinocyte chemoattractant, and macrophage inflammatory protein-2 were significantly increased after single and repetitive dust exposures, but were dampened in 2-wk dust-exposed mice compared with single exposure. Dust exposure induced PKCα and -ε activation in isolated tracheal epithelial cells but were dampened with repetitive exposures. Ex vivo stimulation of alveolar macrophages from 2-wk animals demonstrated reduced cytokine responsiveness and phagocytic ability. Significant lung pathology occurred with development of mixed mononuclear cellular aggregates (T and B lymphocytes, phagocytes) after repetitive dust exposure, a novel observation. Airway hyperresponsiveness to methacholine occurred after single dust exposure but resolved after 2 wk. Collectively, intranasal exposure to DE results in significant lung inflammatory and pathological responses marked by a modulated innate immune response to single and repetitive dust exposures that is associated with PKC activity.
Motion Switching and Chaos of a Particle in a Generalized Fermi‐Acceleration Oscillator
Authors: Luo A. C. J. , Guo Y.
Published: April 2009

Dynamic behaviors of a particle (or a bouncing ball) in a generalized Fermi‐acceleration oscillator are investigated. The motion switching of a particle in the Fermi‐oscillator causes the complexity and unpredictability of motion. Thus, the mechanism of motion switching of a particle in such a generalized Fermi‐oscillator is studied through the theory of discontinuous dynamical systems, and the corresponding analytical conditions for the motion switching are developed. From solutions of linear systems in subdomains, four generic mappings are introduced, and mapping structures for periodic motions can be constructed. Thus, periodic motions in the Fermi‐acceleration oscillator are predicted analytically, and the corresponding local stability and bifurcations are also discussed. From the analytical prediction, parameter maps of periodic and chaotic motions are achieved for a global view of motion behaviors in the Fermi‐acceleration oscillator. Numerical simulations are carried out for illustrations of periodic and chaotic motions in such an oscillator. In existing results, motion switching in the Fermi‐acceleration oscillator is not considered. The motion switching for many motion states of the Fermi‐acceleration oscillator is presented for the first time. This methodology will provide a useful way to determine dynamical behaviors in the Fermi‐acceleration oscillator.
Line‐Source Based X‐Ray Tomography
Authors: Bharkhada Deepak , Yu Hengyong , Liu Hong , Plemmons Robert , Wang Ge
Published: April 2009

Current computed tomography (CT) scanners, including micro‐CT scanners, utilize a point x‐ray source. As we target higher and higher spatial resolutions, the reduced x‐ray focal spot size limits the temporal and contrast resolutions achievable. To overcome this limitation, in this paper we propose to use a line‐shaped x‐ray source so that many more photons can be generated, given a data acquisition interval. In reference to the simultaneous algebraic reconstruction technique (SART) algorithm for image reconstruction from projection data generated by an x‐ray point source, here we develop a generalized SART algorithm for image reconstruction from projection data generated by an x‐ray line source. Our numerical simulation results demonstrate the feasibility of our novel line‐source based x‐ray CT approach and the proposed generalized SART algorithm.
Time as a Quantum Observable, Canonically Conjugated to Energy, and Foundations of Self‐Consistent Time Analysis of Quantum Processes
Authors: Olkhovsky V. S.
Published: April 2009

Recent developments are reviewed and some new results are presented in the study of time in quantum mechanics and quantum electrodynamics as an observable, canonically conjugate to energy. This paper deals with the maximal Hermitian (but nonself‐adjoint) operator for time which appears in nonrelativistic quantum mechanics and in quantum electrodynamics for systems with continuous energy spectra and also, briefly, with the four‐momentum and four‐position operators, for relativistic spin‐zero particles. Two measures of averaging over time and connection between them are analyzed. The results of the study of time as a quantum observable in the cases of the discrete energy spectra are also presented, and in this case the quasi‐self‐adjoint time operator appears. Then, the general foundations of time analysis of quantum processes (collisions and decays) are developed on the base of time operator with the proper measures of averaging over time. Finally, some applications of time analysis of quantum processes (concretely, tunneling phenomena and nuclear processes) are reviewed.
Traitements de la cholestase chronique chez l’enfant
Authors: Alvarez Fernando
Published: April 2009

Peu de traitements spécifiques de la cholestase chronique de l’enfant sont disponibles. La plupart des stratégies thérapeutiques réduisent la rétention des composants de la bile ou pallient certaines des conséquences d’une cholestase chronique. L’acide ursodésoxycholique est l’agent pharmacologique le plus souvent administré chez l’enfant atteint de cholestase chronique. Cet acide biliaire est administré à la posologie de 10 à 30 mg/kg/jour chez les patients présentant une mucoviscidose, des erreurs innées du métabolisme des acides biliaires, une cholestase intrahépatique familiale progressive, une cholangite sclérosante, une atrésie biliaire, un syndrome d’Alagille ou recevant une nutrition parentérale totale. L’acide ursodésoxycholique augmente principalement le débit biliaire et exerce un effet stabilisateur de membrane, ce qui réduit la toxicité des acides biliaires plus hydrophobes. La rifampicine, un antibiotique, à la posologie de 10 à 20 mg/kg/jour est très efficace pour le soulagement du prurit. Des effets similaires sont obtenus au moyen de résines échangeuses d’ions non absorbables. De plus, ces molécules diminuent la cholestérolémie, ce qui contribue à réduire les xanthomes. La compensation de certaines carences créées par une nutrition parentérale totale par l’administration d’acides gras essentiels ou de cystéine peut prévenir les troubles hépatiques associés ou contribuer à leur amélioration. Dans certaines affections cholestatiques, des interventions chirurgicales peuvent faciliter la suppression de l’obstacle à l’écoulement de la bile, comme par exemple la portoentérostomie chez les patients présentant une atrésie des voies biliaires En cas de cholestase intrahépatique, une amélioration clinique et biochimique peut être enregistrée après une dérivation de la bile ou une autre intervention (exclusion de l’iléon) limitant l’absorption des acides biliaires par l’intestin. Dans le futur, l’association de ces différents agents pharmacologiques, accroissement du débit biliaire, protection des membranes cellulaires ou correction de carences nutritionnelles devrait contribuer à une amélioration de la qualité de vie des enfants atteints de cholestase chronique et, par la suite, retarder la nécessité d’un traitement plus drastique comme une transplantation hépatique. Des progrès de la thérapie génique et de la transplantation d’hépatocytes pourraient être également très utiles. Cependant, de nombreuses années d’intenses recherches sont encore nécessaires avant qu’une étude, même pilote, de l’une de ces thérapies puisse être envisagée dans les hépatopathies résponsables d’une cholestase chronique.
The Body Electric: GE, TV, and the Reagan Brand
Authors: Raphael Tim
Published: April 2009

As host of NBC's General Electric Theater from 1954 to 1962, Ronald Reagan enacted a new relationship between popular culture, corporate capitalism, and electronic media. Through his affiliation with General Electric and the celebrity he achieved through television, Reagan played an instrumental role in promoting the re-branding of the imagined community of the American nation as a republic of consumption. This phase of Reagan's career was a crucible for the formation of his political persona and political base.
Verification of Tropical Cyclone–Related Satellite Precipitation Estimates in Mainland China
Authors: Yu Zifeng , Yu Hui , Chen Peiyan , Qian Chuanhai , Yue Caijun
Published: April 2009

To evaluate the abilities of satellite retrievals in reflecting precipitation features related to tropical cyclones (TCs) affecting mainland China, four years of 6- and 24-h precipitation retrievals from three datasets, namely the Tropical Rainfall Measuring Mission satellite algorithm 3B42, version 6 (3B42), Climate Prediction Center morphed (CMORPH) product, and one based on the Geostationary Meteorological Satellite-5 infrared brightness temperature (GMS5-TBB), are compared statistically with direct measurements from surface gauge rainfall data during the periods affected by TCs. The GMS5-TBB dataset was set up by a method of considering the GMS5-TBB characteristics, hourly precipitation intensity, and horizontal distribution for landfalling TCs. The results show that in a general sense, all three satellite-retrieved rainfall datasets give quite reasonable 6- and 24-h rainfall distributions, with skill decreasing with the increase in both latitude and rainfall amount. The 3B42 has a little bit better skill than CMORPH, which is likely related to the fact that the 3B42 product has a rain gauge adjustment and CMORPH does not. Further analyses show that both 3B42 and CMORPH considerably underestimate the moderate and heavy rainfall and overestimate the very light precipitation. The overestimation of the GMS5-TBB data for the light rain is larger than that for 3B42 and CMORPH, probably due to the fact that the GMS5-TBB method considers stratiform and convective rainfall separately with a fixed stratiform rain rate of 2 mm h−1. For the heavy rainfall events, the GMS5-TBB data perform much better than the 3B42 and CMORPH data with an almost halved bias, owing to the fact that the GMS5-TBB method adopted the adjustment of the convective rain rate by considering TBB characteristics of landfalling TCs and using hourly gauge rainfall in the setup process. Since the heavy rainfall events associated with landfalling TCs are of the most concern, the compared GMS5-TBB data could be useful as an operational/research reference.
Interannual Variability of the Global Radiation Budget
Authors: Kato Seiji
Published: April 2009

Interannual variability of the global radiation budget, regions that contribute to its variability, and what limits albedo variability are investigated using Clouds and the Earth’s Radiant Energy System (CERES) data taken from March 2000 through February 2004. Area-weighted mean top-of-atmosphere (TOA) reflected shortwave, longwave, and net irradiance standard deviations computed from monthly anomalies over a 1° × 1° region are 9.6, 7.6, and 7.6 W m−2, respectively. When standard deviations are computed from global monthly anomalies, they drop to 0.5, 0.4, and 0.4 W m−2, respectively. Clouds are mostly responsible for the variation. Regions with a large standard deviation of TOA shortwave and longwave irradiance at TOA are the tropical western and central Pacific, which is caused by shifting from La Niña to El Niño during this period. However, a larger standard deviation of 300–1000-hPa thickness anomalies occurs in the polar region instead of the tropics. The correlation coefficient between atmospheric net irradiance anomalies and 300–1000-hPa thickness anomalies is negative. These indicate that temperature anomalies in the atmosphere are mostly a result of anomalies in longwave and dynamical processes that transport energy poleward, instead of albedo anomalies by clouds directly affecting temperature anomalies in the atmosphere. With simple zonal-mean thermodynamic energy equations it is demonstrated that temperature anomalies decay exponentially with time by longwave emission and by dynamical processes. As a result, the mean meridional temperature gradient is maintained. Therefore, mean meridional circulations are not greatly altered by albedo anomalies on an annual time scale, which in turn provides small interannual variability of the global mean albedo.
Diurnal Cycle of Precipitation in the Tropics Simulated in a Global Cloud-Resolving Model
Authors: Sato Tomonori , Miura Hiroaki , Satoh Masaki , Takayabu Yukari N. , Wang Yuqing
Published: April 2009

This study analyzes the diurnal cycle of precipitation simulated in a global cloud-resolving model (GCRM) named the Nonhydrostatic Icosahedral Atmospheric Model (NICAM). A 30-day integration of NICAM successfully simulates the precipitation diurnal cycle associated with the land–sea breeze and the thermally induced topographic circulations as well as the horizontal propagation of diurnal cycle signals. The first harmonic of the diurnal cycle of precipitation in the 7-km run agrees well with that from satellite observations in its geographical distributions although its amplitude is slightly overestimated. The NICAM simulation revealed that the precipitation diurnal cycle over the Maritime Continent is strongly coupled with the land–sea breeze that controls the convergence/divergence pattern in the lower troposphere around the islands. The analysis also suggests that the cold pool often forms over the open ocean where the precipitation intensity is high, and the propagation of the cold pool events is related to the precipitation diurnal cycle as well as the land–sea breeze.

Sensitivity experiments suggest a prominent horizontal resolution dependence of the simulated precipitation diurnal cycle. Over continental areas the 14-km run induces the diurnal peak about three hours later than the 7-km run. The 3.5-km run produces the peak time and amplitude that are very similar to those in Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) observations. Meanwhile, the resolution dependence in phase and amplitude is negligibly small over the open oceans. This contrast sensitivity to the horizontal resolution is attributed to the differences in structure and life cycle of convective systems over land and ocean.

Diurnal peaks of precipitable water vapor, precipitation, and outgoing longwave radiation (OLR) are compared over land areas using the NICAM 7-km run. The daily precipitable water vapor maximum appears around 1500 local time (LT), which is followed by the precipitation peak around 1630 LT. The diurnal cycle of high clouds tends to peak around 1930 LT, three hours later than the precipitation peak. These results from NICAM simulations can explain the cause of the phase differences among precipitation products based on several satellite observations. The authors demonstrate that the GCRM is a promising tool for realistically simulating the precipitation diurnal cycle and could be quite useful for studying the role of the diurnal cycle in the climate systems in a global context.
The Psychrometric Constant Is Not Constant: A Novel Approach to Enhance the Accuracy and Precision of Latent Energy Fluxes through Automated Water Vapor Calibrations
Authors: Loescher H. W. , Hanson C. V. , Ocheltree T. W.
Published: April 2009

Numerous agencies, programs, and national networks are focused on improving understanding of water and energy fluxes across temporal and spatial scales and on enhancing confidence to synthesize data across multiple sites. Enhancing the accuracy and precision in the surface energy balance and the latent energy (λE) flux lies, in part, with being able to uniformly calibrate water vapor measurements at and among sites to traceable standards. This paper examines (i) the traceable physical controls on field applications of chilled-mirror hygrometers and (ii) an automated means to accurately and precisely calibrate infrared gas analyzers for water vapor concentrations and eddy covariance (λE) data. The environmental physics and gas handling were examined in a theoretical and applied manner that found that chilled-mirror technologies can be a robust measure of dewpoint temperatures and ambient water vapor only if the unit conversions are accounted for between inlet and body temperatures. Psychrometers were also examined and a functional relationship (exponential) was developed for the psychrometric constant against the wet-bulb temperature depression (Tdb − Twb), across a wider range of temperature depressions than previously reported. These empirical estimates of the psychrometer constant for small temperature depressions are much lower than other reported values—that is, ∼0.000 52 K−1 for a wet-bulb temperature depression (Tdb − Twb) of 4.3 K.
Evaluations of NAM Forecasts on Midtropospheric Perturbation-Induced Convective Storms over the U.S. Northern Plains
Authors: Wang Shih-Yu , Chen Tsing-Chang , Taylor S. Elwynn
Published: April 2009

In the U.S. northern plains, summer progressive convective storms that occur in weakly forced environments are often coupled with short-wave perturbations that are embedded in the midlevel northwesterly flow. These midtropospheric perturbations (MPs) are capable of inducing propagating convection that contributes to a majority of the rainfall over the northern plains during July and August. There is a possibility that the difficulties of numerical weather prediction models in forecasting summer convective rainfall over the northern plains are partly attributed to their deficiency in forecasting MPs. The present study tests this possibility through examining operational forecasts by the North American Mesoscale (NAM) model during the summers of 2005 and 2006.

Forecasted MPs exhibit slower propagation speeds and weaker relative vorticity than the observations leading to systematic position errors. Underpredicted vorticity magnitudes weaken horizontal vorticity advection that influences the vorticity tendency throughout the MP life cycle and, in turn, slows the propagation speed of MPs. Moreover, biases of weak ambient flow speed and vortex stretching contribute to the magnitude and propagation speed errors of MPs. Skill scores of precipitation forecasts associated with MPs are low, but can be considerably improved after removing the MP position error that displaces the rainfall pattern. The NAM also tends to underpredict precipitation amounts. A modified water vapor budget analysis reveals that the NAM insufficiently generates atmospheric humidity over the central United States. The shortage of moisture in the forecast reduces the water vapor flux convergence that is part of the precipitation process. The precipitation bias may feed back to affect the MP growth through the bias in heating, thus further slowing the perturbation.
Effects of Statins on the Pharmacokinetics of Midazolam in Healthy Volunteers
Authors: Kokudai Makiko , Inui Naoki , Takeuchi Kazuhiko , Sakaeda Toshiyuki , Kagawa Yoshiyuki , Watanabe Hiroshi
Published: April 2009

Lipid‐lowering agents, 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitors (statins), are widely used to prevent coronary artery disease and often coadministered with other drugs, but there is a possibility that they induce pharmacological interactions with concomitant drugs. The authors aimed to investigate whether statins have any influence on cytochrome P450 (CYP) 3A4 enzyme activity. Eleven healthy volunteers were enrolled and evaluated for the effects of statins on the pharmacokinetics of midazolam in an open‐label, randomized, 3‐way crossover trial with simvastatin 10 mg, atorvastatin 10 mg, and pitavastatin 2 mg. The statins had no effects on the pharmacokinetics of midazolam and its metabolite, 1′‐hydroxymidazolam. Furthermore, the area under the concentration‐time curve ratios for 1′‐hydroxymidazolam/midazolam from 0 to 10 hours showed no significant differences among 3 statins (simvastatin: 0.32 ± 0.09, atorvastatin: 0.31 ± 0.09, and pitavastatin: 0.31 ± 0.12). These data suggest that statins, at least at low doses used in the present study, do not affect CYP3A4 and can be used safely without influencing CAP3A4 enzyme activity.
Clopidogrel Inhibits CYP2C19‐Dependent Hydroxylation of Omeprazole Related to CYP2C19 Genetic Polymorphisms
Authors: Chen B. L. , Chen Y. , Tu J. H. , Li Y. L. , Zhang W. , Li Q. , Fan L. , Tan Z. R. , Hu D. L. , Wang D. , Wang L. S. , OuYang D. S. , Zhou H. H.
Published: April 2009

This study explores the impact of clopidogrel on the pharmacokinetics of omeprazole related to CYP2C19 genetic polymorphisms. Twelve healthy volunteers (6 CYP2C19*1/*1, 5 CYP2C19*2/*2, and 1 CYP2C19*2/*3) are enrolled in a 2‐phase randomized crossover trial. In each phase, the volunteers are administered a single oral dose of omeprazole 40 mg after pretreatment of either placebo or clopidogrel (300 mg on the first day and then 75 mg once daily for 3 consecutive days). Plasma concentrations of omeprazole and its metabolites are quantified by high‐performance liquid chromatography with UV detection. After clopidogrel treatment, the AUC0–∞of omeprazole increases by 30.02% ± 18.03% (P = .004) and that of 5‐hydroxyomeprazole decreases by 24.30% ± 11.66% (P = .032) in CYP2C19*1/*1. The AUC0–∞ratios of omeprazole to 5‐hydroxyomeprazole increase by 74.98% ± 35.48% (P = .001) and those of omeprazole to omeprazole sulfone do not change significantly (P = .832) in CYP2C19*1/*1. No significant alteration is observed in CYP2C19*2/*2 or *3. Clopidogrel inhibits CYP2C19‐dependent hydroxylation of omeprazole in CYP2C19*1/*1 and has no impact on CYP3A4‐catalyzed sulfoxidation of omeprazole.
Inflammatory Mediators in Chinese Patients With Congestive Heart Failure
Authors: Wang Yongqing , Zhou Yanli , Meng Ling , Lu Xinzheng , Ou Ning , Li Xinli
Published: April 2009

In this study, circulating levels of proinflammatory and anti‐inflammatory mediators are studied in patients with chronic heart failure (CHF) in China. Sixty‐five patients with CHF and 32 control subjects are studied. The proinflammatory and anti‐inflammatory cytokines interleukin (IL)‐6, IL‐10, tumor necrosis factor (TNF)‐α, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in plasma are determined by immunoradiometric assay kits. Catecholamine (CA) in plasma is evaluated by high‐performance liquid chromatography. Plasma levels of IL‐6, IL‐10, TNF‐α, ANP, BNP, and CA in CHF patients are significantly higher than those in control subjects. Patients in a higher New York Heart Association (NYHA) class show higher concentrations of inflammatory mediators than those in a lower NYHA class, although the ratio of plasma IL‐10 to TNF‐α in patients with CHF is significantly lower than in the control group. It is concluded that proinflammatory and anti‐inflammatory cytokine levels are increased and IL‐10/TNF‐α is decreased in Chinese patients with CHF.
Phase I Study of the Effect of Gastric Acid pH Modulators on the Bioavailability of Oral Dasatinib in Healthy Subjects
Authors: Eley Timothy , Luo Feng R. , Agrawal Shruti , Sanil Ashish , Manning James , Li Tong , Blackwood‐Chirchir Anne , Bertz Richard
Published: April 2009

Dasatinib is a tyrosine kinase inhibitor (including BCR‐ABL and the SRC family) that is effective in patients with chronic myeloid leukemia. Dasatinib has pH‐dependent solubility and is bioavailable as an oral formulation. The effect of gastric pH modifiers on dasatinib pharmacokinetics is evaluated in an open‐label, randomized, 3‐period, 3‐treatment crossover study. Twenty‐four healthy subjects receive treatment A (2 doses of dasatinib 50 mg separated by 12 hours), treatment B (famotidine 40 mg given 2 hours after dasatinib 50 mg and 10 hours before another dose of dasatinib 50 mg), and treatment C (30 mL of an antacid containing aluminum/magnesium hydroxides given 2 hours before dasatinib 50 mg and concomitantly with dasatinib 50 mg 12 hours after the previous dasatinib dose); a 7‐day washout separates each treatment period. When famotidine is administered 2 hours after dasatinib, dasatinib exposure is similar to dasatinib administered alone. However, dasatinib exposure is reduced by ∼60% when famotidine is administered 10 hours before dasatinib dosing. In contrast, dasatinib exposure is unchanged when antacid (Maalox) is administered 2 hours before dasatinib; but when the antacid is coadministered with dasatinib, dasatinib exposure is reduced by ∼55% to 58%. This indicates that H2‐receptor antagonists should not be coadministered with dasatinib. Dasatinib may be administered with acid‐neutralizing antacids if the doses are temporally separated by at least 2 hours.
Pharmacodynamics Pharmacodynamics of a Novel Designer Natriuretic Peptide, CD‐NP, in a First‐in‐Human Clinical Trial in Healthy Subjects
Authors: Lee Candace Y. W. , Chen Horng H. , Lisy Ondrej , Swan Suzanne , Cannon Courtney , Lieu Hsiao D. , Burnett John C.
Published: April 2009

CD‐NP is a novel chimeric natriuretic peptide (NP) consisting of the 22‐amino‐acid (AA) human C‐type natriuretic peptide (CNP), a venodilating peptide with limited renal actions and minimal effects on blood pressure, and the 15‐AA C‐terminus of Dendroaspis NP (DNP). The rationale for the design of CD‐NP was to enhance the renal actions of CNP, the ligand for natriuretic peptide receptor‐B, but without inducing excessive hypotension. Here we report the first‐in‐human studies for CD‐NP, which represent the first successful clinical testing of a chimeric NP demonstrating in normal human volunteers that CD‐NP possesses cyclic guanosine monophosphate—activating, natriuretic, and aldosterone‐suppressing properties without inducing excessive hypotension, laying the foundation for additional studies on this first‐in‐class new cardiovascular therapeutic in human heart failure, which are now underway worldwide.
Investigation of the accuracy of search engine hit counts
Authors: Uyar Ahmet
Published: April 2009

This study investigates the accuracy of search engine hit counts for search queries. We investigate the accuracy of hit counts for Google, Yahoo and Microsoft Live Search, and the accuracy of single and multiple term queries. In addition, we investigate the consistency of hit count estimates for 15 days. The results show that all three provide estimates for the number of matching documents and the estimation patterns of their counting algorithms differ greatly. The accuracy of hit counts for multiple word queries has not been studied before. The results of our study show that the number of words in queries affects the accuracy of estimations significantly. The percentages of accurate hit count estimations are reduced almost by half when going from single word to two word query tests in all three search engines. With the increase in the number of query words, the error in estimation increases and the number of accurate estimations decreases.
Fenofibrate-Induced Muscular Toxicity Is Associated with a Metabolic Shift Limited to Type-1 Muscles in Rats
Authors: Okada Miyoko , Sano Fumiko , Ikeda Itsuko , Sugimoto Jiro , Takagi Shiro , Sakai Hiroki , Yanai Tokuma
Published: April 2009

Morphological changes and mRNA expression levels in type-1 predominant soleus and type-2 predominant tensor fasciae latae muscles of rats treated with fenofibrate were investigated. After fenofibrate by oral gavage at 300 mg/kg/day for 28 days, degeneration/necrosis and regeneration of muscle fibers, cellular infiltration, and fibrosis were seen in soleus muscle. Additionally, expression of PDK4, CPT1-M, CPT2, and FACO mRNAs was increased. In contrast, no morphological changes or mRNA induction were apparent in tensor fasciae latae muscle. These data suggest that sensitivity to fenofibrate-induced muscle toxicity differs among muscles, with only type-1 fibers being susceptible. The up-regulation of PDK4, CPTs and FACO mRNA expression in soleus muscle indicates that the energy source is switched from glucose to fatty acids, and this might be related to the observed fenofibrate-induced muscular toxicity.
Can atypical antipsychotics improve tardive dyskinesia associated with other atypical antipsychotics? Case report and brief review of the literature
Authors: Peritogiannis V. , Tsouli S.
Published: April 2009

Tardive dyskinesia (TD) is a devastating adverse effect of long-term antipsychotic drug treatment. Atypical antipsychotics produce less TD, and it has been shown that they may have a therapeutic effect on pre-existing TD. Here, we report a case of olanzapine-induced TD which did not improve after switching to risperidone but improved after the addition of quetiapine to risperidone regimen. We also provide a brief review of the reported cases on TD induced by atypical antipsychotics which improved after switching to another atypical agent. It is unclear whether some atypical antipsychotics are more effective than others in the treatment of TD. Differences in this property and the underlying mechanism require further study.
Characterisation of the effects of caffeine on sleep in the rat: a potential model of sleep disruption
Authors: Paterson LM , Wilson SJ , Nutt DJ , Hutson PH , Ivarsson M
Published: April 2009

Abstract

Caffeine is known to disrupt sleep and its administration to human subjects has been used to model sleep disruption. We previously showed that its effects on sleep onset latency are comparable between rats and humans. This study evaluated the potential use of caffeine as a model of sleep disruption in the rat, by assessing its effects on sleep architecture and electroencephalogram (EEG) frequency spectrum, and using sleep-promoting drugs to reverse these effects. Rats were implanted with radiotelemetry devices for body temperature, EEG, electromyogram and locomotor activity. Following recovery, animals were dosed with caffeine (10 mg/kg) alone or in combination with zolpidem (10 mg/kg) or trazodone (20 mg/kg). Sleep was scored for the subsequent 12 h using automated analysis software. Caffeine dose-dependently disrupted sleep: it increased WAKE time, decreased NREM (non-REM) sleep time and NREM bout duration (but not bout number), and decreased delta activity in NREM sleep. It also dose-dependently increased locomotor activity and body temperature. When given alone, zolpidem suppressed REM whilst trazodone increased NREM sleep time at the expense of WAKE, increased NREM bout duration, increased delta activity in NREM sleep and reduced body temperature. In combination, zolpidem attenuated caffeine’s effects on WAKE, whilst trazodone attenuated its effects on NREM sleep, NREM bout duration, delta activity, body temperature and locomotor activity. Caffeine administration produced many of the signs of insomnia that were improved by two of its most successful current treatments. This model may therefore be useful in the study of new drugs for the treatment of sleep disturbance.
Review: Meta-analysis of the effects of lithium usage on serum creatinine levels
Authors: Paul R. , Minay J. , Cardwell C. , Fogarty D. , Kelly C.
Published: April 2009

There is conflicting evidence concerning lithium’s effect on renal function. The aim is to clarify whether lithium affects kidney function and at what stage of treatment any effect may occur. Systematic review identified 23 studies split into three groups on which meta-analysis was performed to identify the following: A) lithium’s effect on renal function in cross-sectional case-control studies, B) studies of renal function before and after commencement on lithium, C) studies of longer term effect in those already established on lithium therapy. Group A showed a statistically significant increase of 5.7 μmol/L in creatinine in the study population compared with controls. Group B showed a non-statistically significant rise in creatinine (2.9 μmol/L) after a mean follow-up of 86 months. Group C showed a statistically significant increase in creatinine of 7.0 μmol/L over a mean duration of 64 months. An increase in creatinine of an average of 1.6 μmol/L/year on lithium was also identified in this group. Any lithium-associated increase in serum creatinine is quantitatively small and of questionable clinical significance. However, routine renal function monitoring of patients on lithium is essential.
Mechanical Performance of Short Banana/Sisal Hybrid Fiber Reinforced Polyester Composites
Authors: Idicula Maries , Joseph Kuruvilla , Thomas Sabu
Published: April 2009

Short randomly oriented banana and sisal hybrid fiber reinforced polyester composites, banana/polyester composites and sisal/polyester composites were fabricated at different fiber loading say, 0.20 to 0.50 Vf. Composites were prepared by varying the relative volume fraction of the two fibers at each fiber loading. When the fiber loading was increased; tensile, flexural, and impact properties increased. Better performance was shown by composites having volume fraction, 0.40 Vf. Tensile strength, tensile modulus, flexural strength, and flexural modulus showed a positive hybrid effect when the volume ratio of the fiber was varied in the hybrid composites at each fiber loading. Maximum tensile strength was observed in composites having volume ratio of banana and sisal 3:1. When the volume ratio of sisal was increased, the impact strength of the composite increased. Different layering patterns were tried at 0.40 Vf, keeping the volume ratio of fibers 1:1. Tensile properties were slightly greater in the trilayer composite with banana as the skin material. Bilayer composites showed higher flexural and impact property. SEM studies were carried out to evaluate fiber/matrix interactions. Experimental results were compared with theoretical predictions.
Physico-Mechanical Properties of Jute Fiber Reinforced Polypropylene Composites
Authors: Rezaur Rahman Md. , Hasan Mahbub , Monimul Huque Md. , Nazrul Islam Md.
Published: April 2009

Jute fiber reinforced polypropylene composites were manufactured using a single extruder and an injection molding machine. Raw jute fiber was oxidized and manufactured composites were post-treated with urea to increase the compatibility of the jute fiber with the polypropylene matrix. Both raw and oxidized jute fiber was utilized and four levels of fiber loading (20, 25, 30, and 35 wt%) was used during composite manufacturing. Microstructural analysis (scanning electron microscopy) and mechanical tests (tensile, flexural, impact, hardness, and water absorption) were conducted. Post-treated jute fiber reinforced specimens yielded better mechanical properties compared to the oxidized and raw ones. Based on fiber loading, 30% fiber reinforced composites had the optimum set of mechanical properties. Authors propose that the bonding between the polypropylene matrix and urea treated jute fiber must be increased in order to have improved mechanical properties at higher fiber content.
The Rheological and Mechanical Properties of Ethylene-Vinyl Acetate (EVA) Copolymer and Organoclay Nanocomposites
Authors: Chacko Annet , Sadiku E.R. , Vorster O.C.
Published: April 2009

Ethylene-vinyl acetate copolymer, EVA (containing 28% vinyl acetate (VA)) and organoclay, tallow benzyl dimethyl ammonium ion with montmorillonite (ranging from 1 to 8 wt%) were melt processed in order to determine the relationship between the polarity of the polymer matrix and the organoclay structure on the properties of the resulting nanocomposites. The effect of clay loading on the rheological and mechanical properties of the nanocomposites is systematically investigated. The intercalated nanocomposites showed a dependence of the properties on the amount of clay loading. Increasing the amount of clay resulted in an improvement in tensile strength and elongation at break. In addition the EVA/clay nanocomposites displayed an enhancement of both storage modulus, E′, and loss modulus, E′′, at low frequencies. Addition of clay decreased the flow activation energy, thereby enhancing the polymer melt flow. Thus clay acted as a lubricant for the EVA polymer.
Synthesis, Characterization and Study of Pine Needles Reinforced Polymer Matrix Based Composites
Authors: Singha A.S. , Vijay Kumar Thakur
Published: April 2009

The aim of the present research article was to study the perspectives of using natural fibers in polymer composites. Keeping in view the enormous advantages of natural fibers, in the present communication a study on the synthesis of pine needles reinforced polymer composites using phenol-formaldehyde (PF) as a novel polymer matrix through compression molding technique has been reported. Effect of fiber loading on mechanical properties such as tensile strength, compressive strength, flexural strength, and wear resistances has also been determined. Reinforcing of the PF resin with pine needles was done in particle form (200 µm). The present study reveals that mechanical properties such as: tensile strength, compressive strength, flexural strength, and wear resistance of the PF resin increases up to 30% fiber loading and then decreases for higher fiber loading when fibers are incorporated into the polymer matrix.
Influence of Sintering Conditions on Densification of YAG—ZrB2 Multi-phase Ceramics with Spark Plasma Sintering
Authors: Song Jie-Guang , Du Da-Ming , Ju Yin-Yan , Xu Ming-Han , Li Shi-Bin , Li Jun-Guo , Zhang Lian-Meng
Published: April 2009

Zirconium diboride (ZrB2) is difficult to prepare as high-density ceramics, which limits its application. To obtain high-density ZrB2 ceramics for improving its high-temperature properties, ZrB 2 particles were coated with Al2O3—Y 2O3 particles to prepare 20%YAG—ZrB2 ceramics with SPS. The optimum sintering condition is a temperature of 1700°C, a pressure of 20 MPa, and a holding time of 4 min. The relative density of prepared 20%YAG—ZrB2 multi-phase ceramics is 97.2% under optimization sintering technology, which indicate that high density YAG—ZrB 2 multi-phase ceramics are successfully prepared.