Course of serum amyloid A (SAA) plasma concentrations in horses undergoing surgery for injuries penetrating synovial structures, an observational clinical study.

PubMed

Haltmayer, Eva; Schwendenwein, Ilse; Licka, Theresia F

2017-05-22

Injuries penetrating synovial structures are common in equine practice and often result in septic synovitis. Significantly increased plasma levels of serum amyloid A (SAA) have been found in various infectious conditions in horses including wounds and septic arthritis. Plasma SAA levels were found to decrease rapidly once the infectious stimulus was eliminated. The purpose of the current study was to investigate the usefulness of serial measurements of plasma SAA as a monitoring tool for the response to treatment of horses presented with injuries penetrating synovial structures. In the current study plasma SAA concentrations were measured every 48 hours (h) during the course of treatment. A total of 19 horses with a wound penetrating a synovial structure were included in the current study. Horses in Group 1 (n = 12) (injuries older than 24 h) only needed one surgical intervention. Patients in this group had significantly lower median plasma SAA levels (P = 0.001) between 48 h (median 776 mg/L) and 96 h (median 202 mg/L) after surgery. A significant decrease (P = 0.004) in plasma SAA levels was also observed between 96 h after surgery (median 270 mg/L) and 6 days (d) after surgery (median 3 mg/L). Four horses (Group 2) required more than one surgical intervention. In contrast to Group 1 patients in Group 2 had either very high initial plasma concentrations (3378 mg/L), an increase or persistently high concentrations of plasma SAA after the first surgery (median 2525 mg/L). A small group of patients (n = 3) (Group 3) were admitted less than 24 h after sustaining a wound. In this group low SAA values at admission (median 23 mg/L) and peak concentrations at 48 h after surgery (median 1016 mg/L) were observed followed by a decrease in plasma SAA concentration over time. A decrease in plasma SAA concentrations between two consecutive time points could be associated with positive response to treatment in the current study. Therefore, serial measurements of plasma SAA could potentially be used as an additional inexpensive, quick and easy tool for monitoring the treatment response in otherwise healthy horses presented with injuries penetrating synovial structures. However further studies will be necessary to ascertain its clinical utility.

Physiological effects of potassium chloride, formalin and handling stress on bonytail

USGS Publications Warehouse

Sykes, Catherine L.; Caldwell, Colleen A.; Gould, William R.

2011-01-01

We characterized the sublethal physiological changes in bonytail Gila elegans subjected to consecutive 750-mg/L potassium chloride (KCl) and 25-mg/L formalin treatments for the removal of zebra mussel Dreissena polymorpha and quagga mussel D. bugensis veligers. Plasma cortisol, glucose, and osmolality were measured over 24 h and at 14 d posthandling after exposing bonytail to KCl and one net stressor (capture with a net), KCl plus formalin and two net stressors, and one or two net stressors without chemicals. Elevated plasma cortisol (322–440 ng/mL) and glucose (254–399 mg/dL) concentrations were observed in all treatments compared with the concentrations in control fish (plasma cortisol, 56 ng/mL; glucose, 43 mg/dL). While there were no detectable differences in plasma osmolality among the treatment and control fish, a difference was observed between fish that were handled once versus twice. Chemical effects of stress were not observed in any of the physiological responses when the KCl treatment was compared with the one-net stressor treatment or when the KCl plus formalin treatment was compared with the two-net stressor treatment. Cumulative responses, however, were observed between one net stressor and two net stressors for plasma glucose and osmolality but not for plasma cortisol. Plasma cortisol and glucose levels remained elevated at 24 h posthandling, indicating that bonytail had not completely recovered from the handling stressors and would benefit from a recovery period in protected refugia before being released.

Plasma treatment induces internal surface modifications of electrospun poly(L-lactic) acid scaffold to enhance protein coating

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin Seo, Hyok; Hee Lee, Mi; Kwon, Byeong-Ju

2013-08-21

Advanced biomaterials should also be bioactive with regard to desirable cellular responses, such as selective protein adsorption and cell attachment, proliferation, and differentiation. To enhance cell-material interactions, surface modifications have commonly been performed. Among the various surface modification approaches, atmospheric pressure glow discharge plasma has been used to change a hydrophobic polymer surface to a hydrophilic surface. Poly(L-lactic acid) (PLLA)-derived scaffolds lack cell recognition signals and the hydrophobic nature of PLLA hinders cell seeding. To make PLLA surfaces more conducive to cell attachment and spreading, surface modifications may be used to create cell-biomaterial interfaces that elicit controlled cell adhesion andmore » maintain differentiated phenotypes. In this study, (He) gaseous atmospheric plasma glow discharge was used to change the characteristics of a 3D-type polymeric scaffold from hydrophobic to hydrophilic on both the outer and inner surfaces of the scaffold and the penetration efficiency with fibronectin was investigated. Field-emission scanning electron microscope images showed that some grooves were formed on the PLLA fibers after plasma treatment. X-ray photoelectron spectroscopy data also showed chemical changes in the PLLA structure. After plasma treatment, -CN (285.76 eV) was increased in C1s and -NH{sub 2} (399.70 eV) was increased significantly and –N=CH (400.80 eV) and –NH{sub 3}{sup +} (402.05 eV) were newly appeared in N1s. These changes allowed fibronectin to penetrate into the PLLA scaffold; this could be observed by confocal microscopy. In conclusion, helium atmospheric pressure plasma treatment was effective in modifying the polymeric scaffold, making it hydrophilic, and this treatment can also be used in tissue engineering research as needed to make polymers hydrophilic.« less

Recent Advances in Velocity Shear Driven Processes

NASA Astrophysics Data System (ADS)

Ganguli, G.

1996-11-01

Macroscopic flows are commonly encountered in a wide variety of plasmas and it is becoming increasingly apparent that the presence of shear in such flows can have a pronounced effect on the nonlinear evolution. For instance, in tokamak devices, sheared poloidal flows are thought to play a crucial role in the L--H transition. In laser-produced plasmas, strongly sheared plasma jets are believed to lead to the onset of intense lower-hybrid waves. In the natural plasma environment of the Earth's ionosphere and magnetosphere, observations indicate a correlation between inhomogeneous flows, plasma wave activity, and particle energization. Different physical processes in which shear-driven phenomenon may dominate span a wide range of spatiotemporal scales. Cross-scale coupling between them can play a vital role in determining the ultimate state of a plasma system which, for space plasmas, is an important factor responsible for the definition of ``space weather.'' Hence, the origin of sheared flows and the plasma response to them is a topic of considerable interest. Ongoing studies indicate that the influence of velocity shear can be generally classified into two broad categories, dissipative and reactive. In the dissipative category, low levels of shear can affect wave-particle interactions through resonance detuning which can substantially modify the normal modes and dispersive properties of a homogeneous plasma. A transverse velocity shear reduces the growth rates of the modes with frequencies lower than the ion-cyclotron frequency while it enhances those modes with frequencies around the ion-cyclotron frequency or larger. Sufficiently strong shear can induce a new class of oscillations via a reactive mechanism by creating neighboring regions with wave energy density of opposite sign. In general, depending on the magnitude and scale length, velocity shear can give rise to plasma oscillations in a very broad frequency and wavelength range. These properties and their applications to space and laboratory plasmas will be discussed.

New Insights Regarding Yeast Survival following Exposure to Liposomal Amphotericin B.

PubMed

Teixeira-Santos, Rita; Ricardo, Elisabete; Guerreiro, Susana Gomes; Costa-de-Oliveira, Sofia; Rodrigues, Acácio Gonçalves; Pina-Vaz, Cidália

2015-10-01

In vitro resistance to amphotericin B is an extremely rare event among pathogenic yeasts. However, in vivo response is sometimes reduced, resulting in an unfavorable outcome. Such adverse outcomes might be related to subfungicidal plasma concentrations. We aimed to clarify the mechanisms of liposomal amphotericin B (AMB-L; AmBisome)-induced lesions and the mechanisms responsible for yeast cell recovery following exposure at plasma concentrations. The physiological statuses developing following exposure to AMB-L at simulated plasma concentrations (20 to 0.1 mg/liter) and at a constant concentration (3 mg/liter) were assessed in a 24-h time course assay. Time-kill experiments also were carried out under the same AMB-L treatment conditions. Our results suggest that yeast cells develop compensatory responses related to membrane polarization, metabolic activity, and reactive oxygen species (ROS) production after exposure to high plasma concentrations (20 to 5 mg/liter) during the first 6 h; in the remaining 18 h, when exposed to lower concentrations, cells reveal almost full recovery with no evidence of fungicidal activity. In contrast, whenever cells are exposed to a constant concentration above the MIC, despite initially exhibiting compensatory stress responses, soon afterwards they exhibit membrane depolarization, a decrease of metabolic activity, increasing ROS production, and lastly, programmed cell death and necrosis, resulting in succumbing to AMB-L fungicidal effects. This study may represent a step forward in the support of AMB-L use for clinical treatment of invasive fungal infections, since it demonstrates the importance of maintaining levels of AMB-L above the MIC in plasma and tissues to ensure it produces its fungicidal effects. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Are ion acoustic waves supported by high-density plasmas in the Large Plasma Device (LaPD)?

NASA Astrophysics Data System (ADS)

Roycroft, Rebecca; Dorfman, Seth; Carter, Troy A.; Gekelman, Walter; Tripathi, Shreekrishna

2012-10-01

Ion acoustic waves are a type of longitudinal wave in a plasma, propagating though the motion of the ions. The wave plays a key role in a parametric decay process thought to be responsible for the spectrum of turbulence observed in the solar wind. In recent LaPD experiments aimed at studying this process, modes thought to be ion acoustic waves are strongly damped when the pump Alfven waves are turned off. This observation motivates an experiment focused on directly launching ion acoustic waves under similar conditions. Our first attempt to launch ion acoustic waves using a metal grid in the plasma was unsuccessful at high magnetic fields and densities due to electrons shorting out the bias applied between the grid and the wall. Results from a new device based on [1] to launch ion acoustic waves will be presented; this device will consist of a small chamber with a plasma source separated from the main chamber by two biased grids. The plasma created inside the small device will be held at a different potential from the main plasma; modulation of this difference should affect the ions, allowing ion acoustic waves to be launched and their properties compared to the prior LaPD experiments.[4pt] [1] W. Gekelman and R. L. Stenzel, Phys. Fluids 21, 2014 (1978).

Predict-first experimental analysis using automated and integrated magnetohydrodynamic modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lyons, B. C.; Paz-Soldan, C.; Meneghini, O.

An integrated-modeling workflow has been developed in this paper for the purpose of performing predict-first analysis of transient-stability experiments. Starting from an existing equilibrium reconstruction from a past experiment, the workflow couples together the EFIT Grad-Shafranov solver [L. Lao et al., Fusion Sci. Technol. 48, 968 (2005)], the EPED model for the pedestal structure [P. B. Snyder et al., Phys. Plasmas 16, 056118 (2009)], and the NEO drift-kinetic-equation solver [E. A. Belli and J. Candy, Plasma Phys. Controlled Fusion 54, 015015 (2012)] (for bootstrap current calculations) in order to generate equilibria with self-consistent pedestal structures as the plasma shape andmore » various scalar parameters (e.g., normalized β, pedestal density, and edge safety factor [q 95]) are changed. These equilibria are then analyzed using automated M3D-C1 extended-magnetohydrodynamic modeling [S. C. Jardin et al., Comput. Sci. Discovery 5, 014002 (2012)] to compute the plasma response to three-dimensional magnetic perturbations. This workflow was created in conjunction with a DIII-D experiment examining the effect of triangularity on the 3D plasma response. Several versions of the workflow were developed, and the initial ones were used to help guide experimental planning (e.g., determining the plasma current necessary to maintain the constant edge safety factor in various shapes). Subsequent validation with the experimental results was then used to revise the workflow, ultimately resulting in the complete model presented here. We show that quantitative agreement was achieved between the M3D-C1 plasma response calculated for equilibria generated by the final workflow and equilibria reconstructed from experimental data. A comparison of results from earlier workflows is used to show the importance of properly matching certain experimental parameters in the generated equilibria, including the normalized β, pedestal density, and q 95. On the other hand, the details of the pedestal current did not significantly impact the plasma response in these equilibria. A comparison to the experimentally measured plasma response shows mixed agreement, indicating that while the equilibria are predicted well, additional analysis tools may be needed. In conclusion, we note the implications that these results have for the success of future predict-first studies, particularly the need for scans of uncertain parameters and for close collaboration between experimentalists and theorists.« less

Predict-first experimental analysis using automated and integrated magnetohydrodynamic modeling

DOE PAGES

Lyons, B. C.; Paz-Soldan, C.; Meneghini, O.; ...

2018-05-07

An integrated-modeling workflow has been developed in this paper for the purpose of performing predict-first analysis of transient-stability experiments. Starting from an existing equilibrium reconstruction from a past experiment, the workflow couples together the EFIT Grad-Shafranov solver [L. Lao et al., Fusion Sci. Technol. 48, 968 (2005)], the EPED model for the pedestal structure [P. B. Snyder et al., Phys. Plasmas 16, 056118 (2009)], and the NEO drift-kinetic-equation solver [E. A. Belli and J. Candy, Plasma Phys. Controlled Fusion 54, 015015 (2012)] (for bootstrap current calculations) in order to generate equilibria with self-consistent pedestal structures as the plasma shape andmore » various scalar parameters (e.g., normalized β, pedestal density, and edge safety factor [q 95]) are changed. These equilibria are then analyzed using automated M3D-C1 extended-magnetohydrodynamic modeling [S. C. Jardin et al., Comput. Sci. Discovery 5, 014002 (2012)] to compute the plasma response to three-dimensional magnetic perturbations. This workflow was created in conjunction with a DIII-D experiment examining the effect of triangularity on the 3D plasma response. Several versions of the workflow were developed, and the initial ones were used to help guide experimental planning (e.g., determining the plasma current necessary to maintain the constant edge safety factor in various shapes). Subsequent validation with the experimental results was then used to revise the workflow, ultimately resulting in the complete model presented here. We show that quantitative agreement was achieved between the M3D-C1 plasma response calculated for equilibria generated by the final workflow and equilibria reconstructed from experimental data. A comparison of results from earlier workflows is used to show the importance of properly matching certain experimental parameters in the generated equilibria, including the normalized β, pedestal density, and q 95. On the other hand, the details of the pedestal current did not significantly impact the plasma response in these equilibria. A comparison to the experimentally measured plasma response shows mixed agreement, indicating that while the equilibria are predicted well, additional analysis tools may be needed. In conclusion, we note the implications that these results have for the success of future predict-first studies, particularly the need for scans of uncertain parameters and for close collaboration between experimentalists and theorists.« less

Predict-first experimental analysis using automated and integrated magnetohydrodynamic modeling

NASA Astrophysics Data System (ADS)

Lyons, B. C.; Paz-Soldan, C.; Meneghini, O.; Lao, L. L.; Weisberg, D. B.; Belli, E. A.; Evans, T. E.; Ferraro, N. M.; Snyder, P. B.

2018-05-01

An integrated-modeling workflow has been developed for the purpose of performing predict-first analysis of transient-stability experiments. Starting from an existing equilibrium reconstruction from a past experiment, the workflow couples together the EFIT Grad-Shafranov solver [L. Lao et al., Fusion Sci. Technol. 48, 968 (2005)], the EPED model for the pedestal structure [P. B. Snyder et al., Phys. Plasmas 16, 056118 (2009)], and the NEO drift-kinetic-equation solver [E. A. Belli and J. Candy, Plasma Phys. Controlled Fusion 54, 015015 (2012)] (for bootstrap current calculations) in order to generate equilibria with self-consistent pedestal structures as the plasma shape and various scalar parameters (e.g., normalized β, pedestal density, and edge safety factor [q95]) are changed. These equilibria are then analyzed using automated M3D-C1 extended-magnetohydrodynamic modeling [S. C. Jardin et al., Comput. Sci. Discovery 5, 014002 (2012)] to compute the plasma response to three-dimensional magnetic perturbations. This workflow was created in conjunction with a DIII-D experiment examining the effect of triangularity on the 3D plasma response. Several versions of the workflow were developed, and the initial ones were used to help guide experimental planning (e.g., determining the plasma current necessary to maintain the constant edge safety factor in various shapes). Subsequent validation with the experimental results was then used to revise the workflow, ultimately resulting in the complete model presented here. We show that quantitative agreement was achieved between the M3D-C1 plasma response calculated for equilibria generated by the final workflow and equilibria reconstructed from experimental data. A comparison of results from earlier workflows is used to show the importance of properly matching certain experimental parameters in the generated equilibria, including the normalized β, pedestal density, and q95. On the other hand, the details of the pedestal current did not significantly impact the plasma response in these equilibria. A comparison to the experimentally measured plasma response shows mixed agreement, indicating that while the equilibria are predicted well, additional analysis tools may be needed. Finally, we note the implications that these results have for the success of future predict-first studies, particularly the need for scans of uncertain parameters and for close collaboration between experimentalists and theorists.

Effects of Carbidopa and Entacapone on the Metabolic Fate of the Norepinephrine Prodrug L-DOPS

PubMed Central

Goldstein, David S.; Holmes, Courtney; Sewell, LaToya; Pechnik, Sandra; Kopin, Irwin J.

2016-01-01

Background L-threo-3,4-dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) prodrug, is investigational for orthostatic hypotension, which occurs commonly in Parkinson’s disease. Adjunctive anti-parkinsonian drugs might interact with L-DOPS. We tested whether L-aromatic aminoacid decarboxylase inhibition by carbidopa (CAR) attenuates L-DOPS conversion to NE and blocks the pressor effect of L-DOPS, whereas catechol-O-methyltransferase inhibition by entacapone (ENT) interferes with L-DOPS metabolism and augments the pressor effect. Methods Twelve patients with autonomic failure took 400 mg of L-DOPS with 200 mg of placebo (PLA), CAR, or ENT on different days. Plasma L-DOPS, NE, and deaminated NE metabolites (dihydroxyphenylglycol [DHPG], dihydroxymandelic acid [DHMA]) were measured. Results L-DOPS+PLA and L-DOPS+ENT increased systolic pressure similarly (by 27 ± 8 and 24 ± 9 mm Hg at 3 hours). L-DOPS+CAR did not increase pressure. The peak increase in plasma NE (0.57 ± 0.11 nmol/L) averaged less than 1/15 000th that in L-DOPS and less than 1/35th that in DHPG+DHMA. CAR prevented and ENT augmented responses of plasma DHPG and DHMA to L-DOPS. Conclusions After L-DOPS administration plasma, NE levels do not increase sufficiently to increase blood pressure. Pressor responses to L-DOPS seem to reflect NE produced extraneuronally that escapes extensive enzymatic deamination and O-methylation and evokes vasoconstriction before reaching the systemic circulation. PMID:20220040

Effects of carbidopa and entacapone on the metabolic fate of the norepinephrine prodrug L-DOPS.

PubMed

Goldstein, David S; Holmes, Courtney; Sewell, LaToya; Pechnik, Sandra; Kopin, Irwin J

2011-01-01

L-threo-3,4-dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) prodrug, is investigational for orthostatic hypotension, which occurs commonly in Parkinson's disease. Adjunctive anti-parkinsonian drugs might interact with L-DOPS. We tested whether L-aromatic amino-acid decarboxylase inhibition by carbidopa (CAR) attenuates L-DOPS conversion to NE and blocks the pressor effect of L-DOPS, whereas catechol-O-methyltransferase inhibition by entacapone (ENT) interferes with L-DOPS metabolism and augments the pressor effect. Twelve patients with autonomic failure took 400 mg of L-DOPS with 200 mg of placebo (PLA), CAR, or ENT on different days. Plasma L-DOPS, NE, and deaminated NE metabolites (dihydroxyphenylglycol [DHPG], dihydroxymandelic acid [DHMA]) were measured. L-DOPS+PLA and L-DOPS+ENT increased systolic pressure similarly (by 27 ± 8 and 24 ± 9 mm Hg at 3 hours). L-DOPS+CAR did not increase pressure. The peak increase in plasma NE (0.57 ± 0.11 nmol/L) averaged less than 1/15,000 th that in L-DOPS and less than 1/35th that in DHPG+DHMA. CAR prevented and ENT augmented responses of plasma DHPG and DHMA to L-DOPS. After L-DOPS administration plasma, NE levels do not increase sufficiently to increase blood pressure. Pressor responses to L-DOPS seem to reflect NE produced extraneuronally that escapes extensive enzymatic deamination and O-methylation and evokes vasoconstriction before reaching the systemic circulation.

F-region and Topside Plasma Response During Geomagnetic Storms

NASA Astrophysics Data System (ADS)

Fuller-Rowell, T. J.; Fedrizzi, M.; Maruyama, N.; Richards, P.; Fang, T. W.; Codrescu, M.

2015-12-01

The noon to dusk mid-latitudes sector appears to be a preferred region for substantial rise in plasma density during elevated geomagnetic activity. Previous the plasma density increase in this sector was referred to as the "dusk effect" and more recently the "storm enhanced density". Certainly in some longitude sectors, if the increase in magnetospheric convection occurs at the appropriate Universal Time, the activity does not need to be particularly strong to produce a significant increase in plasma content, such as during the February 27th 2014 event when Kp reached only 6 but there was substantial loss of the FAA WAAS system. The March 2015 St. Patrick's Day storm was considerably more intense with respect to Kp and Dst, and different in timing and duration, so the response and longitude sectors affected were quite different. Numerical simulation of the St. Patrick's Day storm with a coupled thermosphere-ionosphere model (CTIPe) and a stand-alone ionosphere-plasmasphere code (IPE) can be used to understand the physical processes in the plasma and neutral response. In particular the focus is on the vertical distribution of the plasma from the F-region to the topside. The models can be used to assess the impact of electric fields, meridional neutral winds, and solar illumination aiding plasma buildup and storage, neutral composition creating depletions, and magnetospheric convection creating structure.

Low plasma selenium concentrations in critically ill children: the interaction effect between inflammation and selenium deficiency

PubMed Central

2014-01-01

Introduction Low plasma selenium concentrations are frequent in critically ill patients. However, whether this is due to systemic inflammation, a deficient nutritional state or both is still not clear. We aimed to determine the factors associated with low plasma selenium in critically ill children while considering the inflammatory response and nutritional status. Method A prospective study was conducted in 173 children (median age 34 months) with systemic inflammatory response who had plasma selenium concentrations assessed 48 hours after admission and on the 5th day of ICU stay. The normal reference range was 0.58 μmol/L to 1.6 μmol/L. The outcome variable was ‘low plasma selenium’, which was defined as plasma selenium values below the distribution median during this period. The main explanatory variables were age, malnutrition, sepsis, C-reactive protein (CRP), and clinical severity scores. The data were analyzed using a Binomial Generalized Estimating Equations model, which includes the correlation between admission and 5th day responses. Results Malnutrition and CRP were associated with low plasma selenium. The interaction effect between these two variables was significant. When CRP values were less than or equal to 40 mg/L, malnutrition was associated with low plasma selenium levels (odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.39 to 7.63, P = 0.007; OR = 2.98, 95% CI 1.26 to 7.06, P = 0.013; OR = 2.49, 95% CI 1.01 to 6.17, P = 0.049, for CRP = 10, 20 and 40 mg/L, respectively). This effect decreased as CRP concentrations increased and there was loose significance when CRP values were >40 mg/L. Similarly, the effect of CRP on low plasma selenium was significant for well-nourished patients (OR = 1.13; 95% CI 1.06 to 1.22, P <0.001) but not for the malnourished (OR = 1.03; 95% CI 0.99 to 1.08, P = 0.16). Conclusions There is a significant interaction between the magnitude of the inflammatory response and malnutrition on low plasma selenium. This interaction should be considered when interpreting plasma concentrations as an index of selenium status in patients with systemic inflammation as well as in the decision on selenium supplementation. PMID:24886623

Plasma response measurements of non-axisymmetric magnetic perturbations on DIII-D via soft x-ray imaging

DOE PAGES

Shafer, Morgan W.; Unterberg, Ezekial A.; Wingen, Andreas; ...

2014-12-29

Recent observations on DIII-D have advanced the understanding of plasma response to applied resonant magnetic perturbations (RMPs) in both H-mode and L-mode plasmas. Three distinct 3D features localized in minor radius are imaged via filtered soft x-ray emission: (i) the formation of lobes extending from the unperturbed separatrix in the X-point region at the plasma boundary, (ii) helical kink-like perturbations in the steep-gradient region inside the separatrix, and (iii) amplified islands in the core of a low-rotation L-mode plasma. In this study, these measurements are used to test and to validate plasma response models, which are crucial for providing predictivemore » capability of edge-localized mode control. In particular, vacuum and two-fluid resistive magnetohydrodynamic(MHD) responses are tested in the regions of these measurements. At the plasma boundary in H-mode discharges with n = 3 RMPs applied, measurements compare well to vacuum-field calculations that predict lobe structures. Yet in the steep-gradient region, measurements agree better with calculations from the linear resistive two-fluid MHD code, M3D-C1. Relative to the vacuum fields, the resistive two-fluid MHD calculations show a reduction in the pitch-resonant components of the normal magnetic field (screening), and amplification of non-resonant components associated with ideal kink modes. However, the calculations still over-predict the amplitude of the measuredperturbation by a factor of 4. In a slowly rotating L-mode plasma with n = 1 RMPs, core islands are observed amplified from vacuum predictions. Finally, these results indicate that while the vacuum approach describes measurements in the edge region well, it is important to include effects of extended MHD in the pedestal and deeper in the plasma core.« less

Reflection and backscattering of microwaves under doubling of the plasma density and displacement of the gyroresonance region during electron cyclotron resonance heating of plasma in the l-2M stellarator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Batanov, G. M.; Borzosekov, V. D.; Vasilkov, D. G.

Reflection and backscattering of high-power (400 kW) gyrotron radiation creating and heating plasma at the second harmonic of the electronic cyclotron frequency in the L-2M stellarator have been investigated experimentally. The effect of the displacement of the gyroresonance region from the axis of the plasma column under doubling of the plasma density on the processes of reflection and backscattering of microwave radiation has been examined. A near doubling of short-wavelength (k{sub ⊥} ≈ 30 cm{sup –1}) turbulent density fluctuations squared is observed. The change in the energy confinement time under variations of plasma parameters and characteristics of short-wavelength turbulence ismore » discussed. A discrepancy between the measured values of the reflection coefficient from the electron cyclotron resonance heating region and predictions of the one-dimensional model is revealed.« less

Plasma Generated Spherules

NASA Astrophysics Data System (ADS)

Ransom, C. J.

2005-04-01

Z-pinch plasma simulations have been performed that indicate the production of spherules under certain experimental parameters. (A. L. Peratt, private communication) While performing experiments dealing with the impact of plasma discharges on various materials, we observed that spherules were created at the surface of some of the materials. For specific materials and conditions, spherules were always produced. Both individual spherules and joined spherules were created. The size and shapes were nearly identical to items found by the Mars rover, Opportunity, and called ``blueberries.'' Sky & Telescope, June 2004, p. 20, among other sources indicated the blueberries were gray spherules composed of hematite. The experiments produced hematite spherules identical in appearance to those found on Mars. These experiments suggest how the newly discovered blueberries were formed on Mars while providing an explanation that does not depend on the presence of water.

Women Administered Standard Dose Imatinib for Chronic Myeloid Leukemia Have Higher Dose-Adjusted Plasma Imatinib and Norimatinib Concentrations Than Men.

PubMed

Belsey, Sarah L; Ireland, Robin; Lang, Kathryn; Kizilors, Aytug; Ho, Aloysius; Mufti, Ghulam J; Bisquera, Alessandra; De Lavallade, Hugues; Flanagan, Robert J

2017-10-01

The standard dose of imatinib for the treatment of chronic-phase chronic myeloid leukemia (CML) is 400 mg·d. A predose plasma imatinib concentration of >1 mg·L is associated with improved clinical response. This study aimed to assess the plasma imatinib and norimatinib concentrations attained in patients with chronic myeloid leukemia administered standard doses of imatinib adjusted for dose, age, sex, body weight, and response. We evaluated data from a cohort of patients treated between 2008 and 2014 with respect to dose, age, sex, body weight, and response. The study comprised 438 samples from 93 patients (54 male, 39 female). The median imatinib dose was 400 mg·d in men and in women. The plasma imatinib concentration ranged 0.1-5.0 mg·L and was below 1 mg·L in 20% and 16% of samples from men and women, respectively. The mean dose normalized plasma imatinib and norimatinib concentrations were significantly higher in women in comparison with men. This was partially related to body weight. Mixed effects ordinal logistic regression showed no evidence of an association between sex and plasma imatinib (P = 0.13). However, there was evidence of an association between sex and plasma norimatinib, with higher norimatinib concentrations more likely in women than in men (P = 0.02). Imatinib therapeutic drug monitoring only provides information on dosage adequacy and on short-term adherence; longer-term adherence cannot be assessed. However, this analysis revealed that approximately 1 in 5 samples had a plasma imatinib concentration <1 mg·L, which was suggestive of inadequate dosage and/or poor adherence and posed a risk of treatment failure. Higher imatinib exposure in women may be a factor in the increased rate of long-term, stable, deep molecular response (undetectable breakpoint cluster-Abelson (BCR-ABL) transcript levels with a PCR sensitivity of 4.5 log, MR4.5) reported in women.

Effect of melatonin supplementation on plasma vasopressin response to different conditions in rats with hyperthyroidism induced by L-thyroxine.

PubMed

Mogulkoc, Rasim; Baltaci, Abdulkerim Kasim

2010-04-09

The present study was performed to determine how basal, isotonic, hypertonic and hypovolemic conditions affect fluid-electrolyte balance and plasma arginine vasopressin (AVP) levels in rats with experimental hyperthyroidism supplemented with melatonin. The rats were divided into four groups of twenty-four subjects each kept under the following treatments during one month: (1) Controls; (2) treated with L-thyroxine; (3) treated with L-thyroxine and sham melatonin and (4) treated with L-thyroxine and melatonin. After this each group was further subdivided into subgroups that were subject to normal, isotonic, hypertonic and hypovolemic conditions. The plasma AVP, total triiodothyronine (TT(3)), total thyroxine (TT(4)) and melatonin levels were measured in plasma by means of a Phoenix Pharmaceutical RIA test kit. Hematocrit and osmolality levels were also determined. There were significant increases of total T3 and T4 levels in the L-thyroxine treated groups, p<0.001. The AVP levels were also increased in groups 2 and 3, but not so in the rats treated with melatonin (p<0.001), which also showed increased plasma melatonin levels (p<0.001). These results indicate that treatment with L-thyroxine increases stimulated and non-stimulated AVP release that are inhibited by melatonin supplementation. It was also shown that AVP response to hypertonic and hypovolemic conditions was not affected by L-thyroxine treatment and/or L-thyroxine+melatonin treatment. Copyright 2009 Elsevier B.V. All rights reserved.

D-serine plasma concentration is a potential biomarker of (R,S)-ketamine antidepressant response in subjects with treatment-resistant depression.

PubMed

Moaddel, Ruin; Luckenbaugh, David A; Xie, Ying; Villaseñor, Alma; Brutsche, Nancy E; Machado-Vieira, Rodrigo; Ramamoorthy, Anuradha; Lorenzo, Maria Paz; Garcia, Antonia; Bernier, Michel; Torjman, Marc C; Barbas, Coral; Zarate, Carlos A; Wainer, Irving W

2015-01-01

(R,S)-ketamine is a rapid and effective antidepressant drug that produces a response in two thirds of patients with treatment-resistant depression (TRD). The underlying biochemical differences between a (R,S)-ketamine responder (KET-R) and non-responder (KET-NR) have not been definitively identified but may involve serine metabolism. The aim of the study was to examine the relationship between baseline plasma concentrations of D-serine and its precursor L-serine and antidepressant response to (R,S)-ketamine in TRD patients. Plasma samples were obtained from 21 TRD patients at baseline, 60 min before initiation of the (R,S)-ketamine infusion. Patients were classified as KET-Rs (n = 8) or KET-NRs (n = 13) based upon the difference in Montgomery-Åsberg Depression Rating Scale (MADRS) scores at baseline and 230 min after infusion, with response defined as a ≥50 % decrease in MADRS score. The plasma concentrations of D-serine and L-serine were determined using liquid chromatography-mass spectrometry. Baseline D-serine plasma concentrations were significantly lower in KET-Rs (3.02 ± 0.21 μM) than in KET-NRs (4.68 ± 0.81 μM), p < 0.001. A significant relationship between baseline D-serine plasma concentrations and percent change in MADRS at 230 min was determined using a Pearson correlation, r = 0.77, p < 0.001, with baseline D-serine explaining 60 % of the variance in (R,S)-ketamine response. The baseline concentrations of L-serine (L-Ser) in KET-Rs were also significantly lower than those measured in KET-NRs (66.2 ± 9.6 μM vs 242.9 ± 5.6 μM, respectively; p < 0.0001). The results demonstrate that the baseline D-serine plasma concentrations were significantly lower in KET-Rs than in KET-NRs and suggest that this variable can be used to predict an antidepressant response following (R,S)-ketamine administration.

European Conference on Laser Interaction with Matter (16th ECLIM), Imperial College, London, 26-30 September 1983. Book of Abstracts.

DTIC Science & Technology

1983-09-30

instability by a shaped ion beam M. SAPIR, D. HAVAZALET, Negev, Israel J9 - P Soft X-ray refractometry of laser heated plasmas R. BENATTAR, Ecole...OF STADARDS - ’lS3 - A ,-a J9 SOFT X RAY REFRACTOMETRY OF LASER HEATED PLASMAS R. BENATTAR Laboratoire PMI, Ecole Polytechnique, 91128 Palaiseau...about the more appropriate wavelength to probe the high density region of a laser created plasma by refractometry . After, we show two possibilities, using

Modeling of the L-shell copper X-pinch plasma produced by the compact generator of Ecole polytechnique using pattern recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larour, Jean; Aranchuk, Leonid E.; Danisman, Yusuf

2016-03-15

Principal component analysis is applied and compared with the line ratios of special Ne-like transitions for investigating the electron beam effects on the L-shell Cu synthetic spectra. The database for the principal component extraction is created over a non Local Thermodynamic Equilibrium (non-LTE) collisional radiative L-shell Copper model. The extracted principal components are used as a database for Artificial Neural Network in order to estimate the plasma electron temperature, density, and beam fractions from a representative time-integrated spatially resolved L-shell Cu X-pinch plasma spectrum. The spectrum is produced by the explosion of 25-μm Cu wires on a compact LC (40more » kV, 200 kA, and 200 ns) generator. The modeled plasma electron temperatures are about T{sub e} ∼ 150 eV and N{sub e} = 5 × 10{sup 19} cm{sup −3} in the presence of the fraction of the beams with f ∼ 0.05 and a centered energy of ∼10 keV.« less

Short-term high-fat diet increases postprandial trimethylamine-N-oxide in humans.

PubMed

Boutagy, Nabil E; Neilson, Andrew P; Osterberg, Kristin L; Smithson, Andrew T; Englund, Tessa R; Davy, Brenda M; Hulver, Matthew W; Davy, Kevin P

2015-10-01

The gut microbiota plays an obligatory role in the metabolism of nutrients containing trimethylamine moieties, such as L-carnitine and choline, leading to the production of the proatherogenic trimethylamine-N-oxide (TMAO). We hypothesized that a short-term, high-fat diet would increase fasting and postprandial plasma concentrations of TMAO in response to a high-fat meal challenge. Following a 2-week eucaloric control diet, 10 nonobese men (18-30 years) consumed a eucaloric, high-fat diet (55% fat) for 5 days. Plasma TMAO was measured after a 12-hour fast and each hour after for 4 hours following a high-fat meal (63% fat) at baseline and after the high-fat diet using ultraperformance liquid chromatography/ tandem mass spectrometry. Fasting plasma TMAO did not increase significantly following the high-fat diet (1.83 ± 0.21 vs 1.6 ± 0.24 μmol/L). However, plasma TMAO was higher at hour 1 (2.15 ± 0.28 vs 1.7 ± 0.30 μmol/L), hour 2 (2.3 ± 0.29 vs 1.8 ± 0.32 μmol/L), hour 3 (2.4 ± 0.34 vs 1.58 ± 0.19 μmol/L), and hour 4 (2.51 ± 0.33 vs 1.5 ± 0.12 μmol/L) (all P < .05) following the high-fat diet as compared with the baseline postprandial response. In conclusion, a short-term, high-fat diet does not increase fasting plasma TMAO concentrations but appears to increase postprandial TMAO concentrations in healthy, nonobese, young men. Future studies are needed to determine the mechanisms responsible for these observations. Copyright © 2015 Elsevier Inc. All rights reserved.

A rise in the plasma activities of hepatic enzymes is not a common consequence of hypoglycaemia.

PubMed

Jones, R G; Grant, P J; Brown, D; Stickland, M; Wiles, P G

1988-04-01

Eight otherwise healthy insulin-dependent diabetic patients were subjected to controlled, symptomatic hypoglycaemia for 20 min (median glucose concentration 1.7 mmol/l, range 1.0-2.6 mmol/l). Concentrations of plasma adrenaline and plasma vasopressin were significantly increased, indicating normal counter-regulatory responses for these hormones. Plasma activities of the hepatic enzymes AST, ALT, LDH, GGT, and CK did not increase during or following the period of hypoglycaemia. Thus, abnormal plasma enzyme activities noted after clinical hypoglycaemia should be fully investigated, and not disregarded as due to the hypoglycaemic episode.

Lack of insulinotropic effect of endogenous and exogenous cholecystokinin in man.

PubMed

Reimers, J; Nauck, M; Creutzfeldt, W; Strietzel, J; Ebert, R; Cantor, P; Hoffmann, G

1988-05-01

Intraduodenal phenylalanine administration (333 mg/min over 60 min) released endogenous cholecystokinin in healthy young subjects as demonstrated radioimmunologically and by intraduodenal bilirubin and pancreatic enzyme output. Concomitantly, there was only a small increase over basal in circulating immunoreactive-insulin and immunoreactive-C-peptide concentrations. In healthy volunteers intraduodenal infusions of saline (10 ml/min), glucose (333 mg/min) or phenylalanine (333 mg/min) were performed for 60 min when plasma glucose was clamped at approximately 8 mmol/l. Phenylalanine enhanced immunoreactive-insulin and immunoreactive-C-peptide responses three-fold more than did the same amount of glucose. Immuno-reactive gastric inhibitory polypeptide responses were small and not different after glucose and phenylalanine administration. Immunoreactive cholecystokinin was significantly stimulated to 9.4 +/- 1.4 pmol/l only by intraduodenal phenylalanine. Plasma phenylalanine concentrations increased into the supraphysiological range (approximately 1.5 mmol/l). Intravenous infusions of phenylalanine achieving plasma concentrations of 1.2 mmol/l stimulated insulin secretion at elevated plasma glucose concentrations (approximately 8 mmol/l clamp experiments), but had no effect at basal plasma glucose concentrations. A small increase in cholecystokinin also was observed. Intravenous infusions of synthetic sulphated cholecystokinin-8 leading to plasma concentrations in the upper postprandial range (8-12 pmol/l) did not augment the immunoreactive-insulin or immunoreactive-C-peptide levels during hyperglycaemic clamp experiments, in the absence or presence of elevated plasma phenylalanine concentrations. It is concluded that the augmentation of the glucose-induced insulin release by intraduodenal administration of phenylalanine cannot be related to cholecystokinin release, but rather is explained by the combined effects of elevated glucose and phenylalanine concentrations. In man, cholecystokinin does not augment insulin secretion caused by moderate hyperglycaemia, elevations of phenylalanine concentrations, or combinations thereof.

Measurement of the total antioxidant response in preeclampsia with a novel automated method.

PubMed

Harma, Mehmet; Harma, Muge; Erel, Ozcan

2005-01-10

Preeclampsia is one of the most serious complications of pregnancy. Free radical damage has been implicated in the pathophysiology of this condition. In this study, we aimed to measure the antioxidant capacity in plasma samples from normotensive and preeclamptic pregnant women to evaluate their antioxidant status using a more recently developed automated measurement method. Our study group contained 42 women, 24 of whom had preeclampsia, while 18 had normotensive pregnancies. We measured the total plasma antioxidant capacity for all patients, as well as the levels of four major individual plasma antioxidant components; albumin, uric acid, ascorbic acid and bilirubin, and as a reciprocal measure, their total plasma peroxide levels. Statistically significant differences (determined using Student's t-test) were noted between the normotensive and the preeclamptic groups for their total antioxidant responses and their vitamin C levels (1.31 +/- 0.12 mmol versus 1.06 +/- 0.41 mmol Trolox eq./L; 30.2 +/- 17.83 micromol/L versus 18.1 +/- 11.37 micromol/L, respectively), which were both considerably reduced in the preeclamptic patients. In contrast, the total plasma peroxide levels were significantly elevated in this group (49.8 +/- 14.3 micromol/L versus 38.8 +/- 9.6 micromol/L). We found a decreased total antioxidant response in preeclamptic patients using a simple, rapid and reliable automated colorimetric assay, which may suitable for use in any routine clinical biochemistry laboratory, and considerably facilitates the assessment of this useful clinical parameter. We suggest that this novel method may be used as a routine test to evaluate and follow up of the levels of oxidative stress in preeclampsia.

Association of mutant EGFR L858R and exon 19 concentration in circulating cell-free DNA using droplet digital PCR with response to EGFR-TKIs in NSCLC

PubMed Central

Zhu, Yan-Juan; Zhang, Hai-Bo; Liu, Yi-Hong; Zhu, Ya-Zhen; Chen, Jun; Li, Yong; Bai, Jian-Ping; Liu, Li-Rong; Qu, Yan-Chun; Qu, Xin; Chen, Xian; Zheng, Guang-Juan

2017-01-01

The present study aimed to determine the diagnostic concordance of plasma epidermal growth factor receptor (EGFR) mutation using droplet digital polymerase chain reaction (ddPCR) with tumor tissue samples and the predictive clinical significance of plasma EGFR mutation concentration. Plasma DNA samples from patients with non-small cell lung cancer (NSCLC) were analyzed for EGFR exon 21 codon 858 (L858R) mutation, deletion of exon 19 (ex19del) and exon 20 codon 790 (T790M) mutation using ddPCR. Firstly, the mutations in the plasma samples were compared with the matched tumor samples to determine the concordance. Secondly, image examination follow-ups were analyzed to assess the association between plasma EGFR mutation concentration and patients' response to EGFR-tyrosine kinase inhibitors (TKIs). A total of 51 patients with NSCLC were enrolled, including 48 newly diagnosed patients. Compared with tumor tissue samples, the sensitivity and specificity of ddPCR were 76.19% (16/21) and 96.55% (28/29) for mutant L858R, and 88.89% (8/9) and 100% (41/41) for ex19del, respectively. No patient exhibited the T790M mutation in the tumor tissue or plasma samples. Furthermore, 5 patients with the L858R mutation and 4 patients with ex19del in plasma and tumor tissue samples had been followed up with image examination for ≥3 months following EGFR-TKI treatment. The baseline mutant EGFR concentrations were positively correlated with a reduction in tumor burden (Spearman's r=0.7000, P=0.0358). When analyzed separately, ex19del concentrations (Spearman's r=1.0000, P<0.0001) were also positively correlated with the reduction, while mutant L858R concentrations were not (Spearman's r=0.7000, P=0.1881). In the present study, detection of plasma EGFR mutations using ddPCR exhibited sufficient concordance with tumor tissue sample results. Baseline plasma mutant EGFR and ex19del concentrations were significantly and positively correlated with response to EGFR-TKIs. PMID:28789464

Frequencies and expression levels of programmed death ligand 1 (PD-L1) in circulating tumor RNA (ctRNA) in various cancer types.

PubMed

Ishiba, Toshiyuki; Hoffmann, Andreas-Claudius; Usher, Joshua; Elshimali, Yahya; Sturdevant, Todd; Dang, Mai; Jaimes, Yolanda; Tyagi, Rama; Gonzales, Ronald; Grino, Mary; Pinski, Jacek K; Barzi, Afsaneh; Raez, Luis E; Eberhardt, Wilfried E; Theegarten, Dirk; Lenz, Heinz-Josef; Uetake, Hiroyuki; Danenberg, Peter V; Danenberg, Kathleen

2018-06-07

Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types. Tumors inhibit antitumor response by modulating the immune checkpoint proteins programmed death ligand 1 (PD-L1) and its cognate receptor PD1. The expression of these genes has been implicated in evasion of immune response and resistance to targeted therapies. Blood samples were collected from gastric (GC), colorectal (CRC), lung (NSCLC), breast (BC), prostate cancer (PC) patients, and a healthy control group. ctRNA was purified from fractionated plasma, and following reverse transcription, levels of PD-L1 expression were analyzed using qPCR. PD-L1 expression was detected in the plasma ctRNA of all cancer types at varying frequencies but no PD-L1 mRNA was detected in cancer-free individuals. The frequencies of PD-L1 expression were significantly different among the various cancer types but the median relative PD-L1 expression values were not significantly different. In 12 cases where plasma and tumor tissue were available from the same patients, there was a high degree of concordance between expression of PD-L1 protein in tumor tissues and PD-L1 gene expression in plasma, and both methods were equally predictive of response to nivolumab. PD-L1 mRNA can be detected and quantitated in ctRNA of cancer patients. These results pave the way for further studies aimed at determining whether monitoring the levels of PD-L1 mRNA in blood can identify patients who are most likely to benefit from the conventional treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Cell death induced by ozone and various non-thermal plasmas: therapeutic perspectives and limitations

PubMed Central

Lunov, Oleg; Zablotskii, Vitalii; Churpita, Olexander; Chánová, Eliška; Syková, Eva; Dejneka, Alexandr; Kubinová, Šárka

2014-01-01

Non-thermal plasma has been recognized as a promising tool across a vast variety of biomedical applications, with the potential to create novel therapeutic methods. However, the understanding of the molecular mechanisms behind non-thermal plasma cellular effects remains a significant challenge. In this study, we show how two types of different non-thermal plasmas induce cell death in mammalian cell cultures via the formation of multiple intracellular reactive oxygen/nitrogen species. Our results showed a discrepancy in the superoxide accumulation and lysosomal activity in response to air and helium plasma, suggesting that triggered signalling cascades might be grossly different between different plasmas. In addition, the effects of ozone, a considerable component of non-thermal plasma, have been simultaneously evaluated and have revealed much faster and higher cytotoxic effects. Our findings offer novel insight into plasma-induced cellular responses, and provide a basis for better controlled biomedical applications. PMID:25410636

Creating Extended and Dense Plasma Channels in Air by Using Spatially and Temporally Shaped Ultra-Intense Laser Pulses

DTIC Science & Technology

2011-08-16

Wolf, Phys. Rev. Lett. 104, 103903 (2010). 6. M. Aközbek, M. Scalora , C. Bowden, and S. L. Chin, Opt. Commun. 191, 353 (2001). 7. A. Couairon, Phys...Aközbek, M. Scalora , C. Bowden, and S. L. Chin, “White-light continuum generation and filamentation during the propagation of ultra-short laser pulses in

Exaggerated compensatory response to acute respiratory alkalosis in panic disorder is induced by increased lactic acid production.

PubMed

Ueda, Yoshiyasu; Aizawa, Masayo; Takahashi, Atsushi; Fujii, Masamitsu; Isaka, Yoshitaka

2009-03-01

In acute respiratory alkalosis, the severity of alkalaemia is ameliorated by a decrease in plasma [HCO(3)(-)] of 0.2 mEq/L for each 1 mmHg decrease in PaCO(2). Although hyperventilation in panic disorder patients is frequently encountered in outpatients, the drop in plasma [HCO(3)(-)] sometimes surpasses the expectation calculated from the above formula. The quantitative relationship between reduced PaCO(2) and plasma [HCO(3)(-)] in acute respiratory alkalosis has not been studied in panic disorder patients. Our objective was to provide reference data for the compensatory metabolic changes in acute respiratory alkalosis in panic disorder patients. In 34 panic disorder patients with hyperventilation attacks, we measured arterial pH, PaCO(2), plasma [HCO(3)(-)] and lactate on arrival at the emergency room. For each decrease of 1 mmHg in PaCO(2), plasma [HCO(3)(-)] decreased by 0.41 mEq/L. During hypocapnia, panic disorder patients exhibited larger increases in serum lactate levels (mean +/- SD; 2.59 +/- 1.50 mmol/L, range; 0.78-7.78 mmol/L) than previously reported in non-panic disorder subjects. Plasma lactate accumulation was correlated with PaCO(2) (P < 0.001). These results suggest that the compensatory metabolic response to acute respiratory alkalosis is exaggerated by increased lactic acid production in panic disorder patients. Here, we call attention to the diagnosis of acid-base derangements by means of plasma [HCO(3)(-)] and lactate concentration in panic disorder patients.

Relationship between the von Willebrand Factor Plasma Concentration and Ultrasonographic Doppler Findings in Pregnancies Complicated by Hypertensive Disorders: A Pilot Study.

PubMed

Szpera-Gozdziewicz, Agata; Gozdziewicz, Tomasz; Boruczkowski, Maciej; Dworacki, Grzegorz; Breborowicz, Grzegorz H

2018-01-01

Recent evidence suggests that impaired cytotrophoblast proliferation and migration are major factors responsible for the development of hypertension in pregnancy. Studies report that von Willebrand factor (vWf) is a specific endothelial damage plasma marker. The aim of this study was to evaluate the relationship between vWf maternal plasma concentration and maternal and fetal Doppler flow measurements in pregnancies complicated by hypertension. It may provide additional insight into the pathophysiology of pregnancy-related hypertension and show the potential method for disease prevention and therapy. We created 3 study groups: pregnant women with chronic hypertension (n = 10), gestational hypertension (n = 18), preeclampsia (n = 21), and control (22 healthy pregnant women). Every woman underwent ultrasound Doppler flow measurements performed simultaneously with venous blood collection. The vWf plasma concentrations were assessed using the commercially available enzyme-linked immunosorbent assay kit. The preeclampsia group had significantly higher vWf plasma concentrations in those patients with ultrasonographic features of placental insufficiency than in those without these characteristics (638 ± 208 vs. 377 ± 74 ng/mL; p < 0.017). Our results may confirm the arrangement and severity of endothelial damage in preeclamptic patients and may have identified those patients with a significantly higher risk of developing cardiovascular disease. © 2018 S. Karger AG, Basel.

Acute effect of Clitoria ternatea flower beverage on glycemic response and antioxidant capacity in healthy subjects: a randomized crossover trial.

PubMed

Chusak, Charoonsri; Thilavech, Thavaree; Henry, Christiani Jeyakumar; Adisakwattana, Sirichai

2018-01-08

Clitoria ternatea L., a natural food-colorant containing anthocyanin, demonstrated antioxidant and antihyperglycemic activity. The aim of this study was to determine the effects of Clitoria ternatea flower extract (CTE) on postprandial plasma glycemia response and antioxidant status in healthy men. In a randomized, crossover study, 15 healthy men (ages 22.53 ± 0.30 years; with body mass index of 21.57 ± 0.54 kg/m 2 ) consumed five beverages: (1) 50 g sucrose in 400 mL water; (2) 1 g CTE in 400 mL of water; (3) 2 g CTE in 400 mL of water; (4) 50 g sucrose and 1 g CTE in 400 mL of water; and (5) 50 g sucrose and 2 g CTE in 400 mL of water. Incremental postprandial plasma glucose, insulin, uric acid, antioxidant capacities and lipid peroxidation were measured during 3 h of administration. After 30 min ingestion, the postprandial plasma glucose and insulin levels were suppressed when consuming sucrose plus 1 g and 2 g CTE. In addition, consumption of CTE alone did not alter plasma glucose and insulin concentration in the fasting state. The significant increase in plasma antioxidant capacity (ferric reducing ability of plasma (FRAP), oxygen radical absorbance capacity (ORAC), trolox equivalent antioxidant capacity (TEAC), and protein thiol) and the decrease in malondialdehyde (MDA) level were observed in the subjects who received 1 g and 2 g CTE. Furthermore, consumption of CTE protected sucrose-induced reduction in ORAC and TEAC and increase in plasma MDA. These findings suggest that an acute ingestion of CTE increases plasma antioxidant capacity without hypoglycemia in the fasting state. It also improves postprandial glucose, insulin and antioxidant status when consumed with sucrose. Thai Clinical Trials Registry: TCTR20170609003 . Registered 09 September 2017. 'retrospectively registered'.

Pharmacokinetic-pharmacodynamic profile of systemic nitric oxide-synthase inhibition with L-NMMA in humans

PubMed Central

Mayer, Bernhard X; Mensik, Christa; Krishnaswami, Sriram; Derendorf, Hartmut; Eichler, Hans-Georg; Schmetterer, Leopold; Wolzt, Michael

1999-01-01

Aims It has been demonstrated that inhibition of endothelium derived nitric oxide with NG-monomethyl-l-arginine (l-NMMA) results in a different cardiac and peripheral vascular response. The purpose of this study was to investigate the pharmacokinetic-pharmacodynamic profile of l-NMMA and pharmacokinetic interactions with l-arginine in healthy subjects. Methods Plasma pharmacokinetics were analysed from two different studies: In study 1, 3 mg kg−1 l-NMMA was administered i.v. over 5 min and systemic haemodynamics, cardiac output (CO), fundus pulsation amplitude (FPA), and NO-exhalation (exhNO) were measured at baseline and 15, 65, 95, 155, and 305 min after start of drug administration (n=7). In study 2, 17 mg kg−1 min−1 of the physiologic substrate for nitric oxide synthase, l-arginine, was coinfused i.v. over 30 min with a primed constant infusion of 50 μg kg−1 min−1 l-NMMA (n=8). Results Bolus infusion of l-NMMA resulted in a maximum plasma concentration of 12.9±3.4 μg ml−1 (mean±s.d.) with elimination half-life of 63.5±14.5 min and clearance of 12.2±3.5 ml min−1 kg−1 and caused a small hypertensive response, decreased CO by 13%, FPA by 26%, exhNO by 46% and increased systemic vascular resistance by 16% (P<0.05 each) 15 min after start of drug administration. Although only limited data points were available in the l-NMMA plasma concentration range between 0 and 4 μg ml−1, drug effects over time were in good agreement with an Emax model (r2>0.98 each), which also suggested that concentrations producing half-maximum effects were higher for FPA than for CO and exhNO. The coinfusion with l-arginine caused a nearly two-fold increase in plasma l-NMMA levels, indicating a pharmacokinetic interaction. Conclusions In the absence of a systemic hypertensive response, l-NMMA significantly decreased CO, exhNO, and FPA. The concentration calculated to produce a half maximal effect was equivalent for exhNO and CO, but markedly higher for FPA. Furthermore, measurement of FPA is susceptible to changes in l-NMMA levels at small plasma concentrations. PMID:10336578

Attenuation of acute plasma cortisol response in calves following intravenous sodium salicylate administration prior to castration.

PubMed

Coetzee, J F; Gehring, R; Bettenhausen, A C; Lubbers, B V; Toerber, S E; Thomson, D U; Kukanich, B; Apley, M D

2007-08-01

Pain associated with castration in cattle is an animal welfare concern in beef production. This study examined the effect of oral aspirin and intravenous (i.v.) sodium salicylate on acute plasma cortisol response following surgical castration. Twenty bulls, randomly assigned to the following groups, (i) uncastrated, untreated controls, (ii) castrated, untreated controls, (iii) 50 mg/kg sodium salicylate i.v. precastration and (iv) 50 mg/kg aspirin (acetylsalicylic acid) per os precastration, were blood sampled at 3, 10, 20, 30, 40, 50 min and 1, 1.5, 2, 4, 6, 8, 10 and 12 h postcastration. Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. Data were analyzed using noncompartmental analysis, a simple cosine model, anova and t-tests. Intravenous salicylate V(d(ss)) was 0.18 L/kg, Cl(B) was 3.36 mL/min/kg and t(1/2 lambda) was 0.63 h. Plasma salicylate concentrations above 25 microg/mL coincided with significant attenuation in peak cortisol concentrations (P = 0.029). Peak salicylate concentrations following oral aspirin administration was <10 microg/mL and failed to attenuate cortisol response. Once salicylate concentrations decreased below 5 microg/mL, cortisol response in the castrated groups was significantly higher than uncastrated controls (P = 0.018). These findings have implications for designing drug regimens to provide analgesia during routine animal husbandry procedures.

Glucose Metabolism in High-Risk Subjects for Type 2 Diabetes Carrying the rs7903146 TCF7L2 Gene Variant.

PubMed

Daniele, Giuseppe; Gaggini, Melania; Comassi, Mario; Bianchi, Cristina; Basta, Giuseppina; Dardano, Angela; Miccoli, Roberto; Mari, Andrea; Gastaldelli, Amalia; Del Prato, Stefano

2015-08-01

The mechanisms responsible for contribution of variants in the gene TFC7L2 to the risk for type 2 diabetes (T2DM) remains far from being completely understood, and available studies have generated nonunivocal results. We investigated the postprandial glucose metabolism in subjects at risk for T2DM carrying the TCF7L2 risk allele. Twenty-three subjects carrying the risk-conferring TCF7L2 genotypes (11 TT and 12 CT at rs7901346) and 13 subjects with wild-type genotype (CC) underwent a standard mixed-meal test (MMT) in combination with stable isotope tracers. We evaluated endogenous and exogenous glucose fluxes and hormonal responses. Fasting plasma glucose, insulin, C-peptide, glycated hemoglobin, endogenous glucose production, and plasma glucose clearance were similar in the three groups, whereas plasma glucagon levels were lower in both CT and TT than in CC (64 ± 20, 63 ± 18 and 90 ± 29 pg/mL, respectively; both P = .01). In response to the MMT, TT subjects had lower plasma glucose levels than CC subjects [mean area under the time-concentration curve (AUC) 6.1 ± 3.9 vs 7.1 ± 12.0 mmol/L, P = .04] and lower insulin secretion rate (mean AUC 385 ± 95 vs 530 ± 159 pmol/m(2) · min, P = .02). Initial (0-60 min) rate of appearance (Ra) of oral glucose was lower in TT compared with CT/CC (AUC 2.7 ± 1.1 vs 3.8 ± 1.2 μmol/kg · min, P = .02) with no difference among the three groups in endogenous glucose production. The AUC0-60min for Ra of exogenous glucose (Raex) was positively correlated with the plasma glucose AUC0-60min. Total Raex AUC0-120min was correlated with total AUC0-120min of plasma glucose (r = 0.45, P < .01). Plasma glucagon-like peptide-1 and glucose-dependent insulinotropic peptide levels in response to the MMT were not affected by genotype. In subjects at risk for T2DM, the TCF7L2 polymorphisms were associated with reduced Raex into systemic circulation, causing reduced postprandial blood glucose increase and, in turn, lower insulin secretion rate with no impairment in β-cell function. The reduced Raex is likely due to greater glucose retention in the splanchnic area.

Endogenous opioids inhibit oxytocin release during nicotine-stimulated secretion of vasopressin in man.

PubMed

Seckl, J R; Johnson, M; Shakespear, C; Lightman, S L

1988-05-01

The effects of the opioid antagonist naloxone on the vasopressin (AVP) and oxytocin (OT) responses to nicotine were studied in male non-smokers (21-30 years old). Either saline (n = 6) or naloxone (4 mg bolus + 6 mg/h, n = 6) was infused i.v. during the study. After 60 min infusion the subjects smoked one high-nicotine content cigarette. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Smoking led to a significant rise in plasma vasopressin in both saline and naloxone-infused subjects (P less than 0.05). There was no significant difference in the plasma AVP response to smoking between the two groups. Saline-infused subjects did not show any change in plasma OT in response to smoking. Naloxone infusion was associated with a significant rise in OT from 1.3 +/- 0.1 pmol/l to 4.3 +/- 2.4 pmol/l 5 min after smoking (P less than 0.05). We conclude that there is endogenous opioid-mediated inhibition of OT which prevents its release when AVP is secreted in response to nicotine in man.

Spectral modeling of laser-produced underdense titanium plasmas

NASA Astrophysics Data System (ADS)

Chung, Hyun-Kyung; Back, Christina A.; Scott, Howard A.; Constantin, Carmen; Lee, Richard W.

2004-11-01

Experiments were performed at the NIKE laser to create underdense low-Z plasmas with a small amount of high-Z dopant in order to study non-LTE population kinetics. An absolutely calibrated spectra in 470-3000 eV was measured in time-resolved and time-averaged fashion from SiO2 aerogel target with 3% Ti dopant. K-shell Ti emission was observed as well as L-shell Ti emission. Time-resolved emission show that lower energy photons peak later than higher energy photons due to plasma cooling. In this work, we compare the measured spectra with non-LTE spectral calculations of titanium emission at relatively low temperatures < 1 keV and electron densities from 1e19 to 1e21 cm-3. A temperature diagnostics using the charge state distributions dominated by L-shell ions will be discussed.

Fluxes of Ca2+ and K+ are required for the listeriolysin O-dependent internalization pathway of Listeria monocytogenes.

PubMed

Vadia, Stephen; Seveau, Stephanie

2014-03-01

Listeria monocytogenes is responsible for the life-threatening food-borne disease listeriosis. This disease mainly affects elderly and immunocompromised individuals, causing bacteremia and meningoencephalitis. In pregnant women, L. monocytogenes infection leads to abortion and severe infection of the fetus or newborn. The L. monocytogenes intracellular life cycle is critical for pathogenesis. Previous studies have established that the major virulence factor of L. monocytogenes, the pore-forming toxin listeriolysin O (LLO), is sufficient to induce L. monocytogenes internalization into human epithelial cell lines. This internalization pathway strictly requires the formation of LLO pores in the plasma membrane and can be stimulated by the heterologous pore-forming toxin pneumolysin, suggesting that LLO acts nonspecifically by forming transmembrane pores. The present work tested the hypothesis that Ca2+ and K+ fluxes subsequent to perforation by LLO control L. monocytogenes internalization. We report that L. monocytogenes perforates the host cell plasma membrane in an LLO-dependent fashion at the early stage of invasion. In response to perforation, host cells undergo Ca2+ -dependent but K+ -independent resealing of their plasma membrane. In contrast to the plasma membrane resealing process, LLO-induced L. monocytogenes internalization requires both Ca2+ and K+ fluxes. Further linking ion fluxes to bacterial internalization, treating cells with a combination of Ca2+ and K+ ionophores but not with individual ionophores is sufficient to induce efficient internalization of large cargoes, such as 1-μm polystyrene beads and bacteria. We propose that LLO-induced L. monocytogenes internalization requires a Ca2+ - and K+ -dependent internalization pathway that is mechanistically distinct from the process of plasma membrane resealing.

Constitutive CD40L Expression on B Cells Prematurely Terminates Germinal Center Response and Leads to Augmented Plasma Cell Production in T Cell Areas

PubMed Central

Bolduc, Anna; Long, Eugene; Stapler, Dale; Cascalho, Marilia; Tsubata, Takeshi; Koni, Pandelakis A.; Shimoda, Michiko

2013-01-01

CD40/CD40L engagement is essential to T cell-dependent B cell proliferation and differentiation. However, the precise role of CD40 signaling through cognate T–B interaction in the generation of germinal center and memory B cells is still incompletely understood. To address this issue, a B cell-specific CD40L transgene (CD40LBTg) was introduced into mice with B cell-restricted MHC class II deficiency. Using this mouse model, we show that constitutive CD40L expression on B cells alone could not induce germinal center differentiation of MHC class II-deficient B cells after immunization with T cell-dependent Ag. Thus, some other MHC class II-dependent T cell-derived signals are essential for the generation of germinal center B cells in response to T cell-dependent Ag. In fact, CD40LBTg mice generated a complex Ag-specific IgG1 response, which was greatly enhanced in early, but reduced in late, primary response compared with control mice. We also found that the frequency of Ag-specific germinal center B cells in CD40LBTg mice was abruptly reduced 1 wk after immunization. As a result, the numbers of Ag-specific IgG1 long-lived plasma cells and memory B cells were reduced. By histology, large numbers of Ag-specific plasma cells were found in T cell areas adjacent to Ag-specific germinal centers of CD40LBTg mice, temporarily during the second week of primary response. These results indicate that CD40L expression on B cells prematurely terminated their ongoing germinal center response and produced plasma cells. Our results support the notion that CD40 signaling is an active termination signal for germinal center reaction. PMID:20505142

Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers

PubMed Central

Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica

2014-01-01

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response. PMID:25013355

Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers.

PubMed

Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica; Burgos, Rafael Agustín

2014-01-01

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response.

Formation of the oxygen torus in the inner magnetosphere: Van Allen Probes observations

DOE PAGES

Nose, Masahito; Oimatsu, S.; Keika, K.; ...

2015-02-19

Here we study the formation process of an oxygen torus during the 12–15 November 2012 magnetic storm, using the magnetic field and plasma wave data obtained by Van Allen Probes. We estimate the local plasma mass density (ρ L) and the local electron number density (n eL) from the resonant frequencies of standing Alfvén waves and the upper hybrid resonance band. The average ion mass (M) can be calculated by M ~ ρ L/n eL under the assumption of quasi-neutrality of plasma. During the storm recovery phase, both Probe A and Probe B observe the oxygen torus at L =more » 3.0–4.0 and L = 3.7–4.5, respectively, on the morning side. The oxygen torus has M = 4.5–8 amu and extends around the plasmapause that is identified at L~3.2–3.9. We find that during the initial phase, M is 4–7 amu throughout the plasma trough and remains at ~1 amu in the plasmasphere, implying that ionospheric O + ions are supplied into the inner magnetosphere already in the initial phase of the magnetic storm. Numerical calculation under a decrease of the convection electric field reveals that some of thermal O + ions distributed throughout the plasma trough are trapped within the expanded plasmasphere, whereas some of them drift around the plasmapause on the dawnside. This creates the oxygen torus spreading near the plasmapause, which is consistent with the Van Allen Probes observations. We conclude that the oxygen torus identified in this study favors the formation scenario of supplying O + in the inner magnetosphere during the initial phase and subsequent drift during the recovery phase.« less

Relationship between plasma concentrations of lamotrigine and its early therapeutic effect of lamotrigine augmentation therapy in treatment-resistant depressive disorder.

PubMed

Kagawa, Shoko; Mihara, Kazuo; Nakamura, Akifumi; Nemoto, Kenji; Suzuki, Takeshi; Nagai, Goyo; Kondo, Tsuyoshi

2014-12-01

The relationship between plasma concentrations of lamotrigine and its therapeutic effects was prospectively studied on 34 (9 men and 25 women) inpatients with treatment-resistant depressive disorder during an 8-week treatment of lamotrigine augmentation using an open-study design. The subjects were depressed patients who had already shown insufficient response to at least 3 psychotropics, including antidepressants, mood stabilizers, and atypical antipsychotics. The diagnoses were major depressive disorder (n = 12), bipolar I disorder (n = 7), and bipolar II disorder (n = 15). The final doses of lamotrigine were 100 mg/d for 18 subjects who were not taking valproate and 75 mg/d for 16 subjects taking valproate. Depressive symptoms were evaluated by the Montgomery Åsberg Depression Rating Scale (MADRS) before and after the 8-week treatment. Blood sampling was performed at week 8. Plasma concentrations of lamotrigine were measured by high-performance liquid chromatography. There was a significant linear relationship between the plasma concentrations of lamotrigine and percentage improvements at week 8 (r = 0.418, P < 0.05). A stepwise multiple regression analysis showed that plasma lamotrigine concentrations alone had a significant effect on the percentage improvements at week 8 (standardized partial correlation coefficients = 0.454, P < 0.001). The receiver operating characteristics analysis indicated that a plasma lamotrigine concentration of 12.7 μmol/L or greater was significantly (P < 0.001) predictive of response (50% or more reduction in the MADRS score). The proportion of the responders was significantly higher in the groups with a lamotrigine concentration >12.7 μmol/L (11/15 versus 4/19, P < 0.01). The present study suggests that an early therapeutic response to lamotrigine is dependent on its plasma concentration and that a plasma lamotrigine concentration of 12.7 μmol/L may be a threshold for a good therapeutic response in treatment-resistant depressive disorder.

Enhanced fasting and post-prandial plasma bile acid responses after Roux-en-Y gastric bypass surgery.

PubMed

Werling, Malin; Vincent, Royce P; Cross, Gemma F; Marschall, Hanns-Ulrich; Fändriks, Lars; Lönroth, Hans; Taylor, David R; Alaghband-Zadeh, Jamshid; Olbers, Torsten; Le Roux, Carel W

2013-11-01

Exogenous bile acid (BA) administration is associated with beneficial metabolic effects very similar to those seen after Roux-en-Y gastric bypass (RYGB) surgery. Re-routing of bile into a biliopancreatic limb with simultaneous exclusion of food occurs after RYGB, with subsequent increased fasting plasma BAs. The study assessed fasting and post-prandial plasma BA response before and 15 months after RYGB. The prospective study recruited 63 obese individuals (43 females), aged 43 (36-56) [median (IQR)] years. Blood samples were collected before and every 30 min for 120 min after a standard 400 kcal meal. Fasting and post-prandial plasma BAs, glucagons like peptide-1 (GLP-1), -tyrosine (PYY), fasting C-reactive protein (CRP), glucose and insulin were measured and homeostasis model assessment-insulin resistance (HOMA-IR) was calculated. Following RYGB, body mass index, CRP, fasting glucose and HOMA-IR decreased; 43.7 (39.3-49.2) kg/m(2) to 29.2 (25.1-35.0) kg/m(2), 7.9 (4.1-11.9) mg/L to 0.4 (0.2-1.0) mg/L, 5.5 (5.0-6.0) mmol/L to 4.6 (4.3-4.9) mmol/L and 5.9 (3.5-9.2) to 1.7 (1.1-2.2), respectively, all P < 0.001. Fasting total BAs, GLP-1 and PYY increased after RYGB; 1.69 (0.70-2.56) µmol/L to 2.43 (1.23-3.82) µmol/L (P = 0.02), 6.8 (1.5-15.3) pmol/L to 17.1 (12.6-23.9) pmol/L (P < 0.001) and 4.0 (1.0-7.1) pmol/L to 15.2 (10.0-28.3) pmol/L (P < 0.001), respectively. The area under the curve for post-prandial total BAs, total glycine-conjugated BAs, GLP-1 and PYY were greater after RYGB; 486 (312-732) µmol/L/min versus 1012 (684-1921) µmol/L/min, 315 (221-466) µmol/L/min versus 686 (424-877) µmol/L/min, 3679 (3162-4537) pmol/L/min versus 5347 (4727-5781) pmol/L/min and 1887 (1423-2092) pmol/L/min versus 3296 (2534-3834) pmol/L/min, respectively, all P < 0.0001. Weight loss following RYGB is associated with an increase in post-prandial plasma BA response due to larger amounts of glycine-conjugated BAs. This suggests up regulation of BA production and conjugation after RYGB.

Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure.

PubMed

Goldstein, David S; Holmes, Courtney; Kaufmann, Horacio; Freeman, Roy

2004-12-01

Oral L-threo-3,4-dihydroxyphenylserine (L-DOPS), a synthetic catechol amino acid, increases standing blood pressure and improves standing ability in patients with neurogenic orthostatic hypotension, by conversion of L-DOPS to norepinephrine (NE) outside the brain. This study assessed the pharmacokinetics of L-DOPS, NE, and dihydroxyphenylglycol (DHPG), the main neuronal metabolite of NE, in patients with primary chronic autonomic failure from pure autonomic failure (PAF) or multiple system atrophy (MSA). In 5 MSA and 4 PAF patients, antecubital venous blood was drawn during supine rest and plasma levels of catechols measured at various times for 48 hours after a single oral dose of 400 mg of L-DOPS. Plasma L-DOPS peaked at 1.9 microg/ml (9 micromol/L) about 3 hours after drug administration, followed by a monoexponential decline with a half-time of 2-3 hours in both patient groups. Plasma NE and DHPG also peaked at about 3 hours, but at much lower concentrations (4 and 42 nmol/L). Compared to the MSA group, the PAF group had a smaller calculated volume of distribution of L-DOPS and up to 10-fold lower plasma NE levels at all time points. Plasma NE was above baseline in MSA even at 48 hours after L-DOPS. The relatively long half-time for disappearance of L-DOPS compared to that of NE explains their very different attained plasma concentrations. The similar NE and DHPG responses in PAF and MSA suggests production of NE from LDOPS mainly in non-neuronal cells. Persistent elevation of plasma NE in MSA suggests residual release of NE from sympathetic nerves.

Decreased insulin response in dairy cows following a four-day fast to induce hepatic lipidosis.

PubMed

Oikawa, S; Oetzel, G R

2006-08-01

Negative energy balance has been implicated in the development of fatty liver, insulin resistance, and impaired health in dairy cows. A 4-d fasting model previously was reported to increase liver triglycerides more than 2.5-fold. The purpose of the present study was to evaluate insulin response in this fasting model. Nonlactating, nonpregnant Holstein cows were fasted for 4 d (6 cows) or fed continuously as control cows (4 cows). Samples were collected 5 d before fasting, during fasting, and immediately after the 4-d fast, 8 d after the fast, and 16 d after the fast. Fasted cows had greater liver triglyceride content (49.4 vs. 16.2 mg/g, wet-weight basis) at the end of the fasting period compared with control cows. Fasted cows also had increased plasma nonesterified fatty acid (NEFA) concentrations (1.24 vs. 0.21 mmol/L) and increased plasma beta-hydroxybutyrate (BHBA) concentrations at the end of the fasting period. Liver triglyceride, plasma NEFA, and plasma BHBA in fasted cows returned to prefasting concentrations by the end of the experiment. Plasma glucose concentrations were not affected by fasting. Plasma insulin concentrations were decreased (6.3 vs. 14.1 microU/mL) and insulin-stimulated blood glucose reduction was decreased (24.9 vs. 48.6%) in the fasted cows compared with control cows at the end of the fast, indicating reduced insulin response. Insulin response was negatively correlated with plasma NEFA and liver triglycerides. Decreased insulin response may be an important complication of negative energy balance and hepatic lipidosis.

Marginal Ascorbate Status (Hypovitaminosis C) Results in an Attenuated Response to Vitamin C Supplementation.

PubMed

Carr, Anitra C; Pullar, Juliet M; Bozonet, Stephanie M; Vissers, Margreet C M

2016-06-03

Inadequate dietary intake of vitamin C results in hypovitaminosis C, defined as a plasma ascorbate concentration ≤23 μmol/L. Our objective was to carry out a retrospective analysis of two vitamin C supplementation studies to determine whether supplementation with 50 mg/day vitamin C is sufficient to restore adequate ascorbate status (≥50 μmol/L) in individuals with hypovitaminosis C. Plasma ascorbate data from 70 young adult males, supplemented with 50 or 200 mg/day vitamin C for up to six weeks, was analyzed. Hypovitaminosis C status was identified based on plasma ascorbate being ≤23 μmol/L and the response of these individuals to vitamin C supplementation was examined. Of the participants consuming 50 mg/day vitamin C for up to six weeks, those with hypovitaminosis C at baseline achieved plasma concentrations of only ~30 μmol/L, whereas the remainder reached ~50 μmol/L. Participants who consumed 200 mg/day vitamin C typically reached saturating concentrations (>65 μmol/L) within one week, while those with hypovitaminosis C required two weeks to reach saturation. Regression modelling indicated that the participants' initial ascorbate status and body weight explained ~30% of the variability in the final ascorbate concentration. Overall, our analysis revealed that supplementation with 50 mg/day vitamin C, which resulted in a total dietary vitamin C intake of 75 mg/day, was insufficient to achieve adequate plasma ascorbate concentrations in individuals with hypovitaminosis C. Furthermore, increased body weight had a negative impact on ascorbate status.

Dopa-decarboxylase gene polymorphisms affect the motor response to L-dopa in Parkinson's disease.

PubMed

Devos, David; Lejeune, Stéphanie; Cormier-Dequaire, Florence; Tahiri, Khadija; Charbonnier-Beaupel, Fanny; Rouaix, Nathalie; Duhamel, Alain; Sablonnière, Bernard; Bonnet, Anne-Marie; Bonnet, Cecilia; Zahr, Noel; Costentin, Jean; Vidailhet, Marie; Corvol, Jean-Christophe

2014-02-01

In Parkinson's disease (PD), the response to L-dopa is highly variable and unpredictable. The major pathway for dopamine synthesis from L-dopa is decarboxylation by aromatic L-amino acid decarboxylase (AAAD, encoded by the DDC gene). To determine the motor response to L-dopa in PD patients as a function of the DDC gene promoter polymorphisms (rs921451 T > C polymorphism (DDC(T/C)) and rs3837091 AGAG del (DDC(AGAG/-))). Thirty-three Caucasian PD patients underwent an acute l-dopa challenge together with the peripheral AAAD inhibitor benserazide and were genotyped for rs921451 and rs3837091. The primary efficacy criterion was the motor response to L-dopa, as estimated by the area under the curve for the change in the Unified Parkinson's Disease Rating Scale part III (UPDRS) score relative to baseline (AUCΔUPDRS) in the 4 h following L-dopa administration. Secondary endpoints were pharmacokinetic parameters for plasma levels of L-dopa and dopamine. Investigators and patients were blinded to genotypes data throughout the study. When adjusted for the L-dopa dose, the AUCΔUPDRS was significantly lower in DDC(CC/CT) patients (n = 14) than in DDC(TT) patients (n = 19) and significantly lower in DDC(-/- or AGAG/-) patients (n = 8) than in DDC(AGAG/AGAG) patients (n = 25). There were no significant intergroup differences in plasma pharmacokinetic parameters for L-dopa and dopamine. The rs921451 and rs3837091 polymorphisms of the DDC gene promoter influence the motor response to L-dopa but do not significantly change peripheral pharmacokinetic parameters for L-dopa and dopamine. Our results suggest that DDC may be a genetic modifier of the l-dopa response in Parkinson's disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Formation of a three-dimensional plasma boundary after decay of the plasma response to resonant magnetic perturbation fields

NASA Astrophysics Data System (ADS)

Schmitz, O.; Evans, T. E.; Fenstermacher, M. E.; Lanctot, M. J.; Lasnier, C. L.; Mordijck, S.; Moyer, R. A.; Reimerdes, H.; the DIII-D Team

2014-01-01

First time experimental evidence is presented for a direct link between the decay of a n = 3 plasma response and the formation of a three-dimensional (3D) plasma boundary. We inspect a lower single-null L-mode plasma which first reacts at sufficiently high rotation with an ideal resonant screening response to an external toroidal mode number n = 3 resonant magnetic perturbation field. Decay of this response due to reduced bulk plasma rotation changes the plasma state considerably. Signatures such as density pump out and a spin up of the edge rotation—which are usually connected to formation of a stochastic boundary—are detected. Coincident, striation of the divertor single ionized carbon emission and a 3D emission structure in double ionized carbon at the separatrix is seen. The striated C II pattern follows in this stage the perturbed magnetic footprint modelled without a plasma response (vacuum approach). This provides for the first time substantial experimental evidence, that a 3D plasma boundary with direct impact on the divertor particle flux pattern is formed as soon as the internal plasma response decays. The resulting divertor structure follows the vacuum modelled magnetic field topology. However, the inward extension of the perturbed boundary layer can still not directly be determined from these measurements.

L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug.

PubMed

Goldstein, David S

2006-01-01

L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxydopa) is a synthetic catecholamino acid. When taken orally, L-DOPS is converted to the sympathetic neurotransmitter, norepinephrine (NE), via decarboxylation catalyzed by L-aromatic-amino-acid decarboxylase (LAAAD). Plasma L-DOPS levels peak at about 3 h, followed by a monoexponential decline with a half-time of 2 to 3 h. Plasma levels of NE and of its main neuronal metabolite, dihydroxyphenylglycol (DHPG) peak approximately concurrently but at much lower concentrations. The relatively long half-time for disappearance of L-DOPS from plasma, compared to that of NE, explains their very different attained plasma concentrations. In patients with neurogenic orthostatic hypotension, L-DOPS increases blood pressure and ameliorates orthostatic intolerance. Inhibition of LAAAD, such as by treatment with carbidopa, which does not penetrate the blood-brain barrier, prevents the blood pressure effects of the drug, indicating that L-DOPS increases blood pressure by augmenting NE production outside the brain. Patients with pure autonomic failure (which usually entails loss of sympathetic noradrenergic nerves), and patients with multiple system atrophy (in which noradrenergic innervation remains intact) have similar plasma NE responses to L-DOPS. This suggests mainly non-neuronal production of NE from L-DOPS. L-DOPS is very effective in treatment of deficiency of dopamine-beta-hydroxylase (DBH), the enzyme required for conversion of dopamine to NE in sympathetic nerves. L-DOPS holds promise for treating other much more common conditions involving decreased DBH activity or NE deficiency, such as a variety of syndromes associated with neurogenic orthostatic hypotension.

Effect of pravastatin on responsiveness to N-monomethyl-L-arginine in patients with hypercholesterolaemia.

PubMed

Bayerle-Eder, Michaela; Fuchsjäger-Mayrl, Gabriele; Sieder, Anna; Polska, Elzbieta; Roden, Michael; Stulnig, Thomas; Bischof, Martin G; Waldhäusl, Werner; Schmetterer, Leopold; Wolzt, Michael

2002-01-01

Improvement of endothelial function in hypercholesterolaemia is attributed to lipid lowering and to pleiotropic effects of statin therapy. We investigated whether responsiveness to inhibition of constitutive NO formation with N-monomethyl-L-arginine (L-NMMA) is improved after 7 and 28 days of pravastatin. Twelve female and four male subjects with mild or moderate primary hypercholesterolaemia were randomized to pravastatin (20 mg per oral (p.o.) n=8) or placebo (n=8) in a double blind parallel group design. Vascular responsiveness was studied by intravenous bolus infusions of L-NMMA (cumulative doses of 3 and 6 mg/kg). Mean arterial blood pressure (MAP) and pulse rate (PR) were measured noninvasively, pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation amplitudes (FPA) and renal plasma flow (RPF) was measured by the PAH clearance method. Pravastatin lowered plasma cholesterol levels by 16 and 24% after 7 and 28 days of treatment, respectively (P<0.01). L-NMMA caused comparable changes in MAP, PR and RPF between groups. L-NMMA reduced FPA to a similar extent in both groups before and after 7 days of treatment, but the response to L-NMMA was significantly enhanced after 28 days of pravastatin (21%; P<0.001 vs baseline) and greater than after placebo (15%; P<0.01 vs pravastatin). Pravastatin enhances responsiveness to L-NMMA in the ocular microvasculature. Improved responsiveness is associated with changes in total cholesterol levels.

Plasma Metabolomics Reveal Alterations of Sphingo- and Glycerophospholipid Levels in Non-Diabetic Carriers of the Transcription Factor 7-Like 2 Polymorphism rs7903146

PubMed Central

Kirchhofer, Anna; Grallert, Harald; Krug, Susanne; Kastenmüller, Gabi; Römisch-Margl, Werner; Claussnitzer, Melina; Illig, Thomas; Heier, Margit; Meisinger, Christa; Adamski, Jerzy; Thorand, Barbara; Huth, Cornelia; Peters, Annette; Prehn, Cornelia; Heukamp, Ina; Laumen, Helmut; Lechner, Andreas; Hauner, Hans; Seissler, Jochen

2013-01-01

Aims/Hypothesis Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene have been shown to display a powerful association with type 2 diabetes. The aim of the present study was to evaluate metabolic alterations in carriers of a common TCF7L2 risk variant. Methods Seventeen non-diabetic subjects carrying the T risk allele at the rs7903146 TCF7L2 locus and 24 subjects carrying no risk allele were submitted to intravenous glucose tolerance test and euglycemic-hyperinsulinemic clamp. Plasma samples were analysed for concentrations of 163 metabolites through targeted mass spectrometry. Results TCF7L2 risk allele carriers had a reduced first-phase insulin response and normal insulin sensitivity. Under fasting conditions, carriers of TCF7L2 rs7903146 exhibited a non-significant increase of plasma sphingomyelins (SMs), phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) species. A significant genotype effect was detected in response to challenge tests in 6 SMs (C16:0, C16:1, C18:0, C18:1, C24:0, C24:1), 5 hydroxy-SMs (C14:1, C16:1, C22:1, C22:2, C24:1), 4 lysoPCs (C14:0, C16:0, C16:1, C17:0), 3 diacyl-PCs (C28:1, C36:6, C40:4) and 4 long-chain acyl-alkyl-PCs (C40:2, C40:5, C44:5, C44:6). Discussion Plasma metabolomic profiling identified alterations of phospholipid metabolism in response to challenge tests in subjects with TCF7L2 rs7903146 genotype. This may reflect a genotype-mediated link to early metabolic abnormalities prior to the development of disturbed glucose tolerance. PMID:24205231

Plasma metabolomics reveal alterations of sphingo- and glycerophospholipid levels in non-diabetic carriers of the transcription factor 7-like 2 polymorphism rs7903146.

PubMed

Then, Cornelia; Wahl, Simone; Kirchhofer, Anna; Grallert, Harald; Krug, Susanne; Kastenmüller, Gabi; Römisch-Margl, Werner; Claussnitzer, Melina; Illig, Thomas; Heier, Margit; Meisinger, Christa; Adamski, Jerzy; Thorand, Barbara; Huth, Cornelia; Peters, Annette; Prehn, Cornelia; Heukamp, Ina; Laumen, Helmut; Lechner, Andreas; Hauner, Hans; Seissler, Jochen

2013-01-01

Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene have been shown to display a powerful association with type 2 diabetes. The aim of the present study was to evaluate metabolic alterations in carriers of a common TCF7L2 risk variant. Seventeen non-diabetic subjects carrying the T risk allele at the rs7903146 TCF7L2 locus and 24 subjects carrying no risk allele were submitted to intravenous glucose tolerance test and euglycemic-hyperinsulinemic clamp. Plasma samples were analysed for concentrations of 163 metabolites through targeted mass spectrometry. TCF7L2 risk allele carriers had a reduced first-phase insulin response and normal insulin sensitivity. Under fasting conditions, carriers of TCF7L2 rs7903146 exhibited a non-significant increase of plasma sphingomyelins (SMs), phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs) species. A significant genotype effect was detected in response to challenge tests in 6 SMs (C16:0, C16:1, C18:0, C18:1, C24:0, C24:1), 5 hydroxy-SMs (C14:1, C16:1, C22:1, C22:2, C24:1), 4 lysoPCs (C14:0, C16:0, C16:1, C17:0), 3 diacyl-PCs (C28:1, C36:6, C40:4) and 4 long-chain acyl-alkyl-PCs (C40:2, C40:5, C44:5, C44:6). Plasma metabolomic profiling identified alterations of phospholipid metabolism in response to challenge tests in subjects with TCF7L2 rs7903146 genotype. This may reflect a genotype-mediated link to early metabolic abnormalities prior to the development of disturbed glucose tolerance.

Larger sized wire arrays on 1.5 MA Z-pinch generator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Safronova, A. S., E-mail: alla@unr.edu; Kantsyrev, V. L., E-mail: alla@unr.edu; Weller, M. E., E-mail: alla@unr.edu

Experiments on the UNR Zebra generator with Load Current Multiplier (LCM) allow for implosions of larger sized wire array loads than at standard current of 1 MA. Advantages of larger sized planar wire array implosions include enhanced energy coupling to plasmas, better diagnostic access to observable plasma regions, and more complex geometries of the wire loads. The experiments with larger sized wire arrays were performed on 1.5 MA Zebra with LCM (the anode-cathode gap was 1 cm, which is half the gap used in the standard mode). In particular, larger sized multi-planar wire arrays had two outer wire planes frommore » mid-atomic-number wires to create a global magnetic field (gmf) and plasma flow between them. A modified central plane with a few Al wires at the edges was put in the middle between outer planes to influence gmf and to create Al plasma flow in the perpendicular direction (to the outer arrays plasma flow). Such modified plane has different number of empty slots: it was increased from 6 up to 10, hence increasing the gap inside the middle plane from 4.9 to 7.7 mm, respectively. Such load configuration allows for more independent study of the flows of L-shell mid-atomic-number plasma (between the outer planes) and K-shell Al plasma (which first fills the gap between the edge wires along the middle plane) and their radiation in space and time. We demonstrate that such configuration produces higher linear radiation yield and electron temperatures as well as advantages of better diagnostics access to observable plasma regions and how the load geometry (size of the gap in the middle plane) influences K-shell Al radiation. In particular, K-shell Al radiation was delayed compared to L-shell mid-atomic-number radiation when the gap in the middle plane was large enough (when the number of empty slots was increased up to ten)« less

High-beta extended MHD simulations of stellarators

NASA Astrophysics Data System (ADS)

Bechtel, T. A.; Hegna, C. C.; Sovinec, C. R.; Roberds, N. A.

2016-10-01

The high beta properties of stellarator plasmas are studied using the nonlinear, extended MHD code NIMROD. In this work, we describe recent developments to the semi-implicit operator which allow the code to model 3D plasma evolution with better accuracy and efficiency. The configurations under investigation are an l=2, M=5 torsatron with geometry modeled after the Compact Toroidal Hybrid (CTH) experiment and an l=2, M=10 torsatron capable of having vacuum rotational transform profiles near unity. High-beta plasmas are created using a volumetric heating source and temperature dependent anisotropic thermal conduction and resistivity. To reduce computation expenses, simulations are initialized from stellarator symmetric pseudo-equilibria by turning on symmetry breaking modes at finite beta. The onset of MHD instabilities and nonlinear consequences are monitored as a function of beta as well as the fragility of the magnetic surfaces. Research supported by US DOE under Grant No. DE-FG02-99ER54546.

Therapeutic plasma concentrations of epsilon aminocaproic acid and tranexamic acid in horses.

PubMed

Fletcher, D J; Brainard, B M; Epstein, K; Radcliffe, R; Divers, T

2013-01-01

Antifibrinolytic drugs such as epsilon aminocaproic acid (EACA) and tranexamic acid (TEA) are used to treat various bleeding disorders in horses. Although horses are hypofibrinolytic compared to humans, dosing schemes have been derived from pharmacokinetic studies targeting plasma concentrations in humans. We hypothesized therapeutic plasma concentrations of antifibrinolytic drugs in horses would be significantly lower than in humans. Our objective was to use thromboleastography (TEG) and an in vitro model of hyperfibrinolysis to predict therapeutic concentrations of EACA and TEA in horses and humans. Citrated plasma collected from 24 random source clinically healthy research horses. Commercial pooled human citrated plasma with normal coagulation parameters was purchased. Minimum tissue plasminogen activator (tPA) concentration to induce complete fibrinolysis within 10 minutes was determined using serial dilutions of tPA in equine plasma. Results used to create an in vitro hyperfibrinolysis model with equine and human citrated plasma, and the minimum concentrations of EACA and TEA required to completely inhibit fibrinolysis for 30 minutes (estimated therapeutic concentrations) determined using serial dilutions of the drugs. Estimated therapeutic concentrations of EACA and TEA were significantly lower in horses (5.82; 95% CI 3.77-7.86 μg/mL and 0.512; 95% CI 0.277-0.748 μg/mL) than in humans (113.2; 95% CI 95.8-130.6 μg/mL and 11.4; 95% CI 8.62-14.1 μg/mL). Current dosing schemes for EACA and TEA in horses may be as much as 20× higher than necessary, potentially increasing cost of treatment and risk of adverse effects. Copyright © 2013 by the American College of Veterinary Internal Medicine.

A sensitive LC-MS/MS method for the simultaneous determination of amoxicillin and ambroxol in human plasma with segmental monitoring.

PubMed

Dong, Xin; Ding, Li; Cao, Xiaomei; Jiang, Liyuan; Zhong, Shuisheng

2013-04-01

Amoxicillin (AMO) degrades in plasma at room temperature and readily undergoes hydrolysis by the plasma amidase. In this paper, a novel, rapid and sensitive LC-MS/MS method operated in segmental and multiple reaction monitoring has been developed for the simultaneous determination of amoxicillin and ambroxol in human plasma. The degradation of amoxicillin in plasma was well prevented by immediate addition of 20 μL glacial acetic acid to 200 μL aliquot of freshly collected plasma samples before storage at -80°C. The sensitivity of the method was improved with segmental monitoring of the analytes, and lower limits of quantitation of 0.5 ng/mL for ambroxol and 5 ng/mL for amoxicillin were obtained. The sensitivity of our method was five times better than those of the existing methods. Furthermore, the mass response saturation problem with amoxicillin was avoided by diluting the deproteinized plasma samples with water before injection into the LC-MS/MS system. The method was successfully employed in a pharmacokinetic study of the compound amoxicillin and ambroxol hydrochloride tablets. Copyright © 2012 John Wiley & Sons, Ltd.

Longitudinal monitoring of EGFR mutations in plasma predicts outcomes of NSCLC patients treated with EGFR TKIs: Korean Lung Cancer Consortium (KLCC-12-02).

PubMed

Lee, Ji Yun; Qing, Xu; Xiumin, Wei; Yali, Bai; Chi, Sangah; Bak, So Hyeon; Lee, Ho Yun; Sun, Jong-Mu; Lee, Se-Hoon; Ahn, Jin Seok; Cho, Eun Kyung; Kim, Dong-Wan; Kim, Hye Ryun; Min, Young Joo; Jung, Sin-Ho; Park, Keunchil; Mao, Mao; Ahn, Myung-Ju

2016-02-09

We hypothesized that plasma-based EGFR mutation analysis for NSCLC may be feasible for monitoring treatment response to EGFR TKIs and also predict drug resistance.Clinically relevant mutations including exon 19 deletion (ex19del), L858R and T790M were analyzed using droplet digital PCR (ddPCR) in longitudinally collected plasma samples (n = 367) from 81 NSCLC patients treated with EGFR TKI. Of a total 58 baseline cell-free DNA (cfDNA) samples available for ddPCR analysis, 43 (74.1%) had the same mutation in the matched tumors (clinical sensitivity: 70.8% [17/24] for L858R and 76.5% [26/34] for ex19del). The concordance rates of plasma with tissue-based results of EGFR mutations were 87.9% for L858R and 86.2% for ex19del. All 40 patients who were detected EGFR mutations at baseline showed a dramatic decrease of mutant copies (>50%) in plasma during the first two months after treatment. Median progression-free survival (PFS) was 10.1 months for patients with undetectable EGFR v 6.3 months for detectable EGFR mutations in blood after two-month treatment (HR 3.88, 95% CI 1.48-10.19, P = 0.006). We observed emerging resistance with early detection of T790M as a secondary mutation in 14 (28.6%) of 49 patients. Plasma-based EGFR mutation analysis using ddPCR can monitor treatment response to EGFR TKIs and can lead to early detection of EGFR TKIs resistance. Further studies confirming clinical implications of EGFR mutation in plasma are warranted to guide optimal therapeutic strategies upon knowledge of treatment response and resistance.

Contrasting effects of low versus high ascorbate doses on blood pressure responses to oral nitrite in L-NAME-induced hypertension.

PubMed

Pinheiro, Lucas C; Ferreira, Graziele C; Vilalva, Kelvin H; Toledo, José C; Tanus-Santos, Jose E

2018-04-01

Nitrite reduces blood pressure (BP) in both clinical and experimental hypertension. This effect is attributable to the formation of nitric oxide (NO) and other NO-related species, which may be improved by ascorbate or other antioxidants. However, the BP responses to oral nitrite result, at least in part, of increased gastric S-nitrosothiol formation. This study tested the hypothesis that ascorbate may destroy S-nitrosothiols and therefore not all doses of ascorbate enhance the BP responses to oral nitrite. We assessed the BP responses to oral sodim nitrite (0.2 mmol/kg) in L-NAME hypertensive rats pretreated with ascorbate (0, 0.02, 0.2, or 2 mmol/kg). Plasma and gastric wall concentrations of nitrite and nitroso compounds concentrations were determined using an ozone-based reductive chemiluminescence assay. Nitrate concentrations were determined using the Griess reaction. Free thiol concentrations were determined by a colorimetric assay. The BP responses to nitrite exhibited a bell-shape profile as they were not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg dose attenuated BP responses. In parallel with BP responses, nitrite-induced increases in plasma nitrite and RSNO species were not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg dose attenuated them. Similar experiments were carried out with an equimolar dose of S-nitrosogluthathione. Ascorbate dose-dependently impaired the BP responses to S-nitrosogluthathione, and the corresponding increases in plasma RSNO, but not in plasma nitrite concentrations. This is the first study to show that while ascorbate dose-dependently impairs the BP responses to oral S-nitrosogluthathione, there are contrasting effects when low versus high ascorbate doses are compared with respect to its effects on the blood pressure responses to oral nitrite administration. Our findings may have special implications to patients taking ascorbate, as high doses of this vitamin may impair protective mechanisms associated with nitrite or nitrate from dietary sources. Copyright © 2018 Elsevier Inc. All rights reserved.

Is raised plasma peptide YY after intestinal resection in the rat responsible for the trophic response?

PubMed Central

Savage, A P; Gornacz, G E; Adrian, T E; Ghatei, M A; Goodlad, R A; Wright, N A; Bloom, S R

1985-01-01

The relationship between the adaptive response and plasma PYY concentrations after small bowel resection has been investigated. Seventy five per cent proximal small bowel resection resulted in a rise in plasma PYY at six days from 28 +/- 3.1 to 85 +/- 12.3 pmol/l (p less than 0.001) and this difference was maintained to 48 days. Plasma PYY correlates both with crypt cell production rate (CCPR) in the ileum and with plasma enteroglucagon levels. In a second study, PYY or saline was infused over a 12 day period. There were no significant changes in intestinal wet weight or CCPR in any part of the bowel studied. This indicates that it is unlikely that PYY exerts a major trophic effect on the gastrointestinal tract. PMID:3841330

Is raised plasma peptide YY after intestinal resection in the rat responsible for the trophic response?

PubMed

Savage, A P; Gornacz, G E; Adrian, T E; Ghatei, M A; Goodlad, R A; Wright, N A; Bloom, S R

1985-12-01

The relationship between the adaptive response and plasma PYY concentrations after small bowel resection has been investigated. Seventy five per cent proximal small bowel resection resulted in a rise in plasma PYY at six days from 28 +/- 3.1 to 85 +/- 12.3 pmol/l (p less than 0.001) and this difference was maintained to 48 days. Plasma PYY correlates both with crypt cell production rate (CCPR) in the ileum and with plasma enteroglucagon levels. In a second study, PYY or saline was infused over a 12 day period. There were no significant changes in intestinal wet weight or CCPR in any part of the bowel studied. This indicates that it is unlikely that PYY exerts a major trophic effect on the gastrointestinal tract.

Plasma concentration-dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone-21-isonicotinate.

PubMed

Ekstrand, C; Bondesson, U; Gabrielsson, J; Hedeland, M; Kallings, P; Olsén, L; Ingvast-Larsson, C

2015-06-01

Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03 mg/kg) was administered intramuscularly to six horses. Plasma was analysed for dexamethasone and hydrocortisone and urine for dexamethasone, using UPLC-MS/MS. Dexamethasone was quantifiable in plasma for 8.3 ± 2.9 days (LLOQ: 0.025 μg/L) and in urine for 9.8 ± 3.1 days (LLOQ: 0.15 μg/L). Maximum observed dexamethasone concentration in plasma was 0.61 ± 0.12 μg/L and in urine 4.2 ± 0.9 μg/L. Terminal plasma half-life was 38.7 ± 19 h. Hydrocortisone was significantly suppressed for 140 h. The plasma half-life of hydrocortisone was 2.7 ± 1.3 h. Dexamethasone potency, efficacy and sigmoidicity factor for hydrocortisone suppression were 0.06 ± 0.04 μg/L, 0.95 ± 0.04 and 6.2 ± 4.6, respectively. Hydrocortisone suppression relates to the plasma concentration of dexamethasone. Thus, determination of irrelevant plasma concentrations and SL is possible. Future research will determine whether hydrocortisone suppression can be used as a biomarker of the clinical effect of dexamethasone. © 2014 John Wiley & Sons Ltd.

Evaluation of propylene glycol and glycerol infusions as treatments for ketosis in dairy cows.

PubMed

Piantoni, P; Allen, M S

2015-08-01

To evaluate propylene glycol (PG) and glycerol (G) as potential treatments for ketosis, we conducted 2 experiments lasting 4 d each in which cows received one bolus infusion per day. Blood was collected before infusion, over 240min postinfusion, as well as 24 h postinfusion. Experiment 1 used 6 ruminally cannulated cows (26±7 d in milk) randomly assigned to 300-mL infusions of PG or G (both ≥99.5% pure) in a crossover design experiment with 2 periods. Within each period, cows were assigned randomly to infusion site sequence: abomasum (A)-cranial reticulorumen (R) or the reverse, R-A. Glucose precursors were infused into the R to simulate drenching and the A to prevent metabolism by ruminal microbes. Glycerol infused in the A increased plasma glucose concentration the most (15.8mg/dL), followed by PG infused in the R (12.6mg/dL), PG infused in the A (9.11mg/dL), and G infused in the R (7.3mg/dL). Infusion of PG into the R increased plasma insulin and insulin area under the curve (AUC) the most compared with all other treatments (7.88 vs. 2.13μIU/mL and 321 vs. 31.9min×μIU/mL, respectively). Overall, PG decreased plasma BHBA concentration after infusion (-6.46 vs. -4.55mg/dL) and increased BHBA AUC (-1,055 vs. -558min ×mg/dL) compared with G. Plasma NEFA responses were not different among treatments. Experiment 2 used 8 ruminally cannulated cows (22±5 d in milk) randomly assigned to treatment sequence in a Latin square design experiment balanced for carryover effects. Treatments were 300mL of PG, 300mL of G, 600mL of G (2G), and 300mL of PG + 300mL of G (GPG), all infused into the R. Treatment contrasts compared PG with each treatment containing glycerol (G, 2G, and GPG). Propylene glycol increased plasma glucose (14.0 vs. 5.35mg/dL) and insulin (7.59 vs. 1.11μIU/mL) concentrations compared with G, but only tended to increase glucose and insulin concentrations compared with 2G. Propylene glycol increased AUC for glucose (1,444 vs. 94.3mg/dL) and insulin (326 vs. 6.58min×μIU/mL) compared with G, and tended to increase insulin AUC compared with 2G. Propylene glycol was not different from GPG for glucose, insulin, or BHBA responses. Propylene glycol decreased plasma BHBA concentration (-10.3 vs. -4.21mg/dL) and increased BHBA AUC (-1,578 vs. -1.42min ×mg/dL) compared with G, but not compared with 2G. In general, and compared with G, GPG decreased plasma NEFA concentrations after infusions and PG decreased plasma NEFA concentrations early but not late after infusions. We conclude that a 300-mL dose of PG is more effective at increasing plasma glucose concentration than G and at least as effective as 600mL of G or a combination of G and PG when administered in the cranial reticulorumen. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The energy confinement response of DIII-D plasmas to Resonant Magnetic Perturbations

DOE PAGES

Cui, L.; Nazikian, Raffi; Grierson, B. A.; ...

2017-07-11

Here, Resonant Magnetic Perturbations (RMPs) are a leading method for edge localized modes (ELMs) Control in fusion plasmas. However they can also cause a rapid degradation in energy confinement. In this paper we show that the energy confinement in low collisionality (v* e < 0.3) DIII-D ITER Similar Shape (ISS) plasmas often recovers after several energy confinement times for RMP amplitudes up to the threshold for ELM suppression. Immediately following the application of the RMP, the plasma stored energy decreases in proportion to the decrease in the line-averaged density during density "pump-out". Later in the discharge confinement recovery is observedmore » in the thermal ion channel and is correlated with the increase in the ion temperature at the top of the H-mode pedestal. A correlation between the inverse scale length of the ion temperature (α/L Ti) and the E x B shearing rate at the top of the pedestal is seen during the confinement recovery phase. Transport analysis reveals that the confinement improvement in the ion channel results from the self-similarity in the ion temperature profiles in the plasma core combined with the observed increase in α/L Ti in the plasma edge following density pump-out. In contrast the electron temperature scale length (α/L Ti) remains essentially unchanged in response to the application of the RMP. At significantly higher RMP levels the edge EXB shearing rate and α/L Ti does not increase and the confinement does not recover following density pump-out.« less

Hepatic CREB3L3 controls whole-body energy homeostasis and improves obesity and diabetes.

PubMed

Nakagawa, Yoshimi; Satoh, Aoi; Yabe, Sachiko; Furusawa, Mika; Tokushige, Naoko; Tezuka, Hitomi; Mikami, Motoki; Iwata, Wakiko; Shingyouchi, Akiko; Matsuzaka, Takashi; Kiwata, Shiori; Fujimoto, Yuri; Shimizu, Hidehisa; Danno, Hirosuke; Yamamoto, Takashi; Ishii, Kiyoaki; Karasawa, Tadayoshi; Takeuchi, Yoshinori; Iwasaki, Hitoshi; Shimada, Masako; Kawakami, Yasushi; Urayama, Osamu; Sone, Hirohito; Takekoshi, Kazuhiro; Kobayashi, Kazuto; Yatoh, Shigeru; Takahashi, Akimitsu; Yahagi, Naoya; Suzuki, Hiroaki; Yamada, Nobuhiro; Shimano, Hitoshi

2014-12-01

Transcriptional regulation of metabolic genes in the liver is the key to maintaining systemic energy homeostasis during starvation. The membrane-bound transcription factor cAMP-responsive element-binding protein 3-like 3 (CREB3L3) has been reported to be activated during fasting and to regulate triglyceride metabolism. Here, we show that CREB3L3 confers a wide spectrum of metabolic responses to starvation in vivo. Adenoviral and transgenic overexpression of nuclear CREB3L3 induced systemic lipolysis, hepatic ketogenesis, and insulin sensitivity with increased energy expenditure, leading to marked reduction in body weight, plasma lipid levels, and glucose levels. CREB3L3 overexpression activated gene expression levels and plasma levels of antidiabetic hormones, including fibroblast growth factor 21 and IGF-binding protein 2. Amelioration of diabetes by hepatic activation of CREB3L3 was also observed in several types of diabetic obese mice. Nuclear CREB3L3 mutually activates the peroxisome proliferator-activated receptor (PPAR) α promoter in an autoloop fashion and is crucial for the ligand transactivation of PPARα by interacting with its transcriptional regulator, peroxisome proliferator-activated receptor gamma coactivator-1α. CREB3L3 directly and indirectly controls fibroblast growth factor 21 expression and its plasma level, which contributes at least partially to the catabolic effects of CREB3L3 on systemic energy homeostasis in the entire body. Therefore, CREB3L3 is a therapeutic target for obesity and diabetes.

Chemical Changes in Nonthermal Plasma-Treated N-Acetylcysteine (NAC) Solution and Their Contribution to Bacterial Inactivation.

PubMed

Ercan, Utku K; Smith, Josh; Ji, Hai-Feng; Brooks, Ari D; Joshi, Suresh G

2016-02-02

In continuation of our previous reports on the broad-spectrum antimicrobial activity of atmospheric non-thermal dielectric barrier discharge (DBD) plasma treated N-Acetylcysteine (NAC) solution against planktonic and biofilm forms of different multidrug resistant microorganisms, we present here the chemical changes that mediate inactivation of Escherichia coli. In this study, the mechanism and products of the chemical reactions in plasma-treated NAC solution are shown. UV-visible spectrometry, FT-IR, NMR, and colorimetric assays were utilized for chemical characterization of plasma treated NAC solution. The characterization results were correlated with the antimicrobial assays using determined chemical species in solution in order to confirm the major species that are responsible for antimicrobial inactivation. Our results have revealed that plasma treatment of NAC solution creates predominantly reactive nitrogen species versus reactive oxygen species, and the generated peroxynitrite is responsible for significant bacterial inactivation.

Chemical Changes in Nonthermal Plasma-Treated N-Acetylcysteine (NAC) Solution and Their Contribution to Bacterial Inactivation

PubMed Central

Ercan, Utku K.; Smith, Josh; Ji, Hai-Feng; Brooks, Ari D.; Joshi, Suresh G.

2016-01-01

In continuation of our previous reports on the broad-spectrum antimicrobial activity of atmospheric non-thermal dielectric barrier discharge (DBD) plasma treated N-Acetylcysteine (NAC) solution against planktonic and biofilm forms of different multidrug resistant microorganisms, we present here the chemical changes that mediate inactivation of Escherichia coli. In this study, the mechanism and products of the chemical reactions in plasma-treated NAC solution are shown. UV-visible spectrometry, FT-IR, NMR, and colorimetric assays were utilized for chemical characterization of plasma treated NAC solution. The characterization results were correlated with the antimicrobial assays using determined chemical species in solution in order to confirm the major species that are responsible for antimicrobial inactivation. Our results have revealed that plasma treatment of NAC solution creates predominantly reactive nitrogen species versus reactive oxygen species, and the generated peroxynitrite is responsible for significant bacterial inactivation. PMID:26832829

Effects of two weeks of topical budesonide treatment on microvascular exudative responsiveness in healthy human nasal airways.

PubMed

Greiff, L; Andersson, M; Svensson, C; Akerlund, A; Alkner, U; Persson, C G

1997-04-01

Extravasation and luminal entry of plasma (mucosal exudation) is not only a key feature of airway inflammation in rhinitis and asthma but also a major first-line respiratory defence mechanism. Topical steroids are effective antiexudative agents in disease but, so far, little is known about the direct effects of these drugs on the responsiveness of the microcirculation in human airways. In this study, the effects of prolonged budesonide treatment on histamine-induced mucosal exudation of plasma was examined in 42 healthy subjects. Placebo and budesonide (100 microg per nasal cavity b.i.d.) were given for 2 weeks in a double-blind and placebo-controlled parallel-group protocol. Using a nasal pool technique, nasal challenges with isotonic saline and histamine (40 and 400 microg x mL(-1)) were carried out before and late in the treatment periods. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. Histamine produced concentration-dependent mucosal exudation of plasma before as well as after treatment with either placebo or budesonide. The topical steroid treatment only marginally (1.8 fold) decreased the response to the low concentration histamine (40 microg x mL(-1)) and, although it was significantly (2.8 fold) reduced, histamine 400 microg x mL(-1) still produced significant mucosal exudation of plasma in the budesonide group. If the present observations are extrapolated to inflammatory conditions, the antiexudative effects of topical steroids in rhinitis (and asthma) may reflect only a small degree of microvascular antipermeability effects. We suggest that topical steroid treatment may not impede mucosal exudation responses when called for in acute human airway defence reactions.

Association of blood eosinophils and plasma periostin with FEV1 response after 3-month inhaled corticosteroid and long-acting beta2-agonist treatment in stable COPD patients

PubMed Central

Park, Hye Yun; Lee, Hyun; Koh, Won-Jung; Kim, Seonwoo; Jeong, Ina; Koo, Hyeon-Kyoung; Kim, Tae-Hyung; Kim, Jin Woo; Kim, Woo Jin; Oh, Yeon-Mok; Sin, Don D; Lim, Seong Yong; Lee, Sang-Do

2016-01-01

Background COPD patients with increased airway eosinophilic inflammation show a favorable response to inhaled corticosteroids (ICS) in combination with a long-acting bronchodilator. Recent studies have demonstrated a significant correlation of sputum eosinophilia with blood eosinophils and periostin. We investigated whether high blood eosinophils and plasma periostin were associated with an improvement in forced expiratory volume in 1 second (FEV1) after 3-month treatment with ICS/long-acting beta2-agonist (LABA) in stable COPD patients. Patients and methods Blood eosinophils and plasma periostin levels were measured in 130 stable COPD subjects selected from the Korean Obstructive Lung Disease cohort. Subjects began a 3-month ICS/LABA treatment after washout period. Results High blood eosinophils (>260/µL, adjusted odds ratio =3.52, P=0.009) and high plasma periostin (>23 ng/mL, adjusted odds ratio =3.52, P=0.013) were significantly associated with FEV1 responders (>12% and 200 mL increase in FEV1 from baseline after treatment). Moreover, the addition of high blood eosinophils to age, baseline positive bronchodilator response, and FEV1 <50% of the predicted value significantly increased the area under the curve for prediction of FEV1 responders (from 0.700 to 0.771; P=0.045). Conclusion High blood eosinophils and high plasma periostin were associated with improved lung function after 3-month ICS/LABA treatment. In particular, high blood eosinophils, in combination with age and baseline lung function parameters, might be a possible biomarker for identification of COPD patients with favorable FEV1 improvement in response to ICS/LABA treatment. PMID:26730185

Association of blood eosinophils and plasma periostin with FEV1 response after 3-month inhaled corticosteroid and long-acting beta2-agonist treatment in stable COPD patients.

PubMed

Park, Hye Yun; Lee, Hyun; Koh, Won-Jung; Kim, Seonwoo; Jeong, Ina; Koo, Hyeon-Kyoung; Kim, Tae-Hyung; Kim, Jin Woo; Kim, Woo Jin; Oh, Yeon-Mok; Sin, Don D; Lim, Seong Yong; Lee, Sang-Do

2016-01-01

COPD patients with increased airway eosinophilic inflammation show a favorable response to inhaled corticosteroids (ICS) in combination with a long-acting bronchodilator. Recent studies have demonstrated a significant correlation of sputum eosinophilia with blood eosinophils and periostin. We investigated whether high blood eosinophils and plasma periostin were associated with an improvement in forced expiratory volume in 1 second (FEV1) after 3-month treatment with ICS/long-acting beta2-agonist (LABA) in stable COPD patients. Blood eosinophils and plasma periostin levels were measured in 130 stable COPD subjects selected from the Korean Obstructive Lung Disease cohort. Subjects began a 3-month ICS/LABA treatment after washout period. High blood eosinophils (>260/µL, adjusted odds ratio =3.52, P=0.009) and high plasma periostin (>23 ng/mL, adjusted odds ratio =3.52, P=0.013) were significantly associated with FEV1 responders (>12% and 200 mL increase in FEV1 from baseline after treatment). Moreover, the addition of high blood eosinophils to age, baseline positive bronchodilator response, and FEV1 <50% of the predicted value significantly increased the area under the curve for prediction of FEV1 responders (from 0.700 to 0.771; P=0.045). High blood eosinophils and high plasma periostin were associated with improved lung function after 3-month ICS/LABA treatment. In particular, high blood eosinophils, in combination with age and baseline lung function parameters, might be a possible biomarker for identification of COPD patients with favorable FEV1 improvement in response to ICS/LABA treatment.

Fast vaporization solid phase microextraction and ion mobility spectrometry: A new approach for determination of creatinine in biological fluids.

PubMed

Jafari, Mostafa; Ebrahimzadeh, Homeira; Banitaba, Mohamma Hossein

2015-11-01

In this work a rapid and simple method for creatinine determination in urine and plasma samples based on aqueous derivatization of creatinine and complete vaporization of sample (as low as 10 µL), followed by ion mobility spectrometry analysis has been proposed. The effect of four important parameters (extraction temperature, total volume of solution, desorption temperature and extraction time) on ion mobility signal has been studied. Under the optimized conditions, the quantitative response of ion mobility spectrometry for creatinine was linear in the range of 0-500 mg L(-1) with a detection limit of 0.6 mg L(-1) in urine and 0-250 mg L(-1) with a detection limit of 2.6 mg L(-1) in plasma sample. The limit of quantitation of creatinine was 2.1 mg L(-1) and 8.7 mg L(-1) in urine and plasma samples, respectively. The relative standard deviation of the method was found to be 13%. The method was successfully applied to the analysis of creatinine in biological samples, showing recoveries from 92% to 104% in urine and 101-110% in plasma samples. Copyright © 2015 Elsevier B.V. All rights reserved.

The Lunar dusty plasmas -levitation and transport.

NASA Astrophysics Data System (ADS)

Atamaniuk, Barbara; Rothkaehl, Hanna

Lunar dust can exhibit unusual behavior -due to electron photoemission via solar-UV radiation the lunar surface represents a complex plasma -"dusty plasma". The dust grains and lunar surface are electrostatically charged by the Moon's interaction with the local plasma environ-ment and the photoemission of electrons due to solar UV and X-rays. This effect causes the like-charged surface and dust particles to repel each other, and creates a near-surface electric field. Lunar dust must be treated as a dusty plasma. Using analytic (kinetic (Vlasov) and magnetohydrodynamic theory ) and numerical modeling we show physical processes related to levitation and transport dusty plasma on the Moon. These dust grains could affect the lunar environment for radio wave and plasma diagnostics and interfere with exploration activities. References: 1. Wilson T.L. (1992), in Analysis of Interplanetary Dust, M. Zolensky et al. AIP Conf.Proc. 310, 33-44 (AIP, NY), 2.Wilson T.L."LUNAR DUST AND DUSTY PLASMA PHYSICS".40th Lunar and Planetary Science Conference (2009), 3. Grün E., et al.(1993),Nature 363, 144. 4. Morfill G. and Grün E.(1979), Planet. Space Sci.. 27, 1269, 1283, 5. Manka R. and Michel F. (1971), Proc. 2nd Lun. Sci. Conf. 2, 1717 (MIT Press, Cambridge). 6. Manka R. et al.(1973), Lun. Sci.-III, 504. 7. Barbara Atamaniuk "Kinetic Description of Localized Plasma Structure in Dusty Plasmas". Czechoslovak Journal of Physics Vol.54 C 2004

Particle Acceleration, Magnetic Field Generation, and Emission in Relativistic Pair Jets

NASA Technical Reports Server (NTRS)

Nishikawa, K.-I.; Ramirez-Ruiz, E.; Hardee, P.; Hededal, C.; Mizuno, Y.

2005-01-01

Shock acceleration is a ubiquitous phenomenon in astrophysical plasmas. Plasma waves and their associated instabilities (e.g., the Buneman instability, two-streaming instability, and the Weibel instability) created by relativistic pair jets are responsible for particle (electron, positron, and ion) acceleration. Using a 3-D relativistic electromagnetic particle (REMP) code, we have investigated particle acceleration associated with a relativistic jet propagating through an ambient plasma with and without initial magnetic fields. The growth rates of the Weibel instability depends on the distribution of pair jets. Simulations show that the Weibel instability created in the collisionless shock accelerates particles perpendicular and parallel to the jet propagation direction. The simulation results show that this instability is responsible for generating and amplifying highly nonuniform, small-scale magnetic fields, which contribute to the electron's transverse deflection behind the jet head. The "jitter" radiation from deflected electrons has different properties than synchrotron radiation which is calculated in a uniform magnetic field. This jitter radiation may be important to understanding the complex time evolution and/or spectral structure in gamma-ray bursts, relativistic jets, and supernova remnants.

Plasma Dictionary Website

NASA Astrophysics Data System (ADS)

Correll, Don; Heeter, Robert; Alvarez, Mitch

2000-10-01

In response to many inquiries for a list of plasma terms, a database driven Plasma Dictionary website (plasmadictionary.llnl.gov) was created that allows users to submit new terms, search for specific terms or browse alphabetic listings. The Plasma Dictionary website contents began with the Fusion & Plasma Glossary terms available at the Fusion Energy Educational website (fusedweb.llnl.gov). Plasma researchers are encouraged to add terms and definitions. By clarifying the meanings of specific plasma terms, it is envisioned that the primary use of the Plasma Dictionary website will be by students, teachers, researchers, and writers for (1) Enhancing literacy in plasma science, (2) Serving as an educational aid, (3) Providing practical information, and (4) Helping clarify plasma writings. The Plasma Dictionary website has already proved useful in responding to a request from the CRC Press (www.crcpress.com) to add plasma terms to its CRC physics dictionary project (members.aol.com/physdict/).

Assessing Effects of Oxidizer Characteristics on Composite Reaction Kinetics

DTIC Science & Technology

2013-12-01

in its spark gap is ionized and creates conductive plasma allowing current flow to the EBW. The EBW is a type of detonator which utilizes shockwaves...flow rate of 70 mL min-1 for the remainder of the cycle. Sintering can occur during heating and melting, ultimately affecting heat transfer in the...argon at a flow rate of 70 mL min-1 for the remainder of the cycle. Sintering can occur during heating and melting, ultimately affecting heat transfer

Evidence of L-mode electromagnetic wave pumping of ionospheric plasma near geomagnetic zenith

NASA Astrophysics Data System (ADS)

Leyser, Thomas B.; James, H. Gordon; Gustavsson, Björn; Rietveld, Michael T.

2018-02-01

The response of ionospheric plasma to pumping by powerful HF (high frequency) electromagnetic waves transmitted from the ground into the ionosphere is the strongest in the direction of geomagnetic zenith. We present experimental results from transmitting a left-handed circularly polarized HF beam from the EISCAT (European Incoherent SCATter association) Heating facility in magnetic zenith. The CASSIOPE (CAScade, Smallsat and IOnospheric Polar Explorer) spacecraft in the topside ionosphere above the F-region density peak detected transionospheric pump radiation, although the pump frequency was below the maximum ionospheric plasma frequency. The pump wave is deduced to arrive at CASSIOPE through L-mode propagation and associated double (O to Z, Z to O) conversion in pump-induced radio windows. L-mode propagation allows the pump wave to reach higher plasma densities and higher ionospheric altitudes than O-mode propagation so that a pump wave in the L-mode can facilitate excitation of upper hybrid phenomena localized in density depletions in a larger altitude range. L-mode propagation is therefore suggested to be important in explaining the magnetic zenith effect.

Properties of Plasma Membrane from Pea Root Seedlings under Altered Gravity

NASA Astrophysics Data System (ADS)

Klymchuk, D.; Baranenko, V.; Vorobyova, T. V.; Kurylenko, I.; Chyzhykova, O.; Dubovoy, V.

In this study, the properties of pea (Pisum sativum L.) plasma membrane were examined to determine how the membrane structure and functions are regulated in response to clinorotation (2 rev/min) conditions. Membrane preparations enriched by plasma membrane vesicles were obtained by aqueous two-phase partitioning from 6-day seedling roots. The specific characteristics of H^+-ATPase, lípid composition and peroxidation intensity as well as fluidity of lipid bilayer were analysed. ATP hydrolytic activity was inhibited by ortovanadate and was insensitive to aside and nitrate in sealed plasma membrane vesicles isolated from both clinorotated and control seedlings. Plasma membrane vesicles from clinorotated seedlings in comparison to controls were characterised by increase in the total lipid/protein ratio, ATP hydrolytic activity and intensifying of lipid peroxidation. Sitosterol and campesterol were the predominant free sterol species. Clinorotated seedlings contained a slightly higher level of unsaturated fatty acid than controls. Plasma membrane vesicles were labelled with pyrene and fluorescence originating from monomeric (I_M) molecules and excimeric (I_E) aggregates were measured. The calculated I_E/I_M values were higher in clinorotated seedlings compared with controls reflecting the reduction in membrane microviscosity. The involvement of the changes in plasma membrane lipid content and composition, fluidity and H^+-ATPase activity in response of pea seedlings to altered gravity is discussed.

Changes in nitric oxide release in vivo in response to vasoactive substances.

PubMed Central

Nava, E.; Wiklund, N. P.; Salazar, F. J.

1996-01-01

1. Changes in the release of nitric oxide (NO) in vivo were studied in rats following the administration of endothelium-dependent and -independent vasodilators as well as the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). NO production was assessed by measuring variations of nitrate in plasma by capillary ion analysis. 2. Intravenous administration of the endothelium-dependent vasodilators, bradykinin (2 and 10 micrograms kg-1 min-1) or substance P (0.3-3 micrograms kg-1 min-1) caused a transient dose-dependent hypotension followed by an increase in plasma nitrate concentration (maximal increments: 33 +/- 5% and 38 +/- 6%, for bradykinin and substance P, respectively). Prior administration of L-NAME (10 mg kg-1 min-1) inhibited the hypotension and increase in plasma nitrate caused by these substances. Intravenous administration of sodium nitrate (200 micrograms kg-1) also produced a transitory elevation in plasma nitrate which was similar in magnitude as that caused by the vasodilators. A rapid and transitory increment in plasma nitrate was observed after i.v. administration of authentic NO (400 micrograms kg-1). 3. Rats receiving the endothelium-dependent vasodilators, prostacyclin (0.6 micrograms kg-1 min-1) or adenosine (3 mg kg-1 min-1) intravenously showed a drop in blood pressure paralleled by a decrease in plasma nitrate (maximal decreases: 34 +/- 5% and 24 +/- 4%, for prostacyclin and adenosine, respectively). A similar effect on the plasmatic concentration of nitrate was observed when L-NAME (10 mg kg-1 min-1, i.v.) was administered to the animals. 4. This study demonstrates that (i) changes in plasma nitrate can be detected in vivo after stimulation or inhibition of NO synthase, (ii) an increased production of NO, measured as plasma nitrate, is related to the hypotension caused by bradykinin and substance P and (iii) a diminished concentration of plasmatic nitrate is associated to the hypotension induced by adenosine or prostacyclin (endothelium-independent vasodilators), suggesting that the L-arginine: NO pathway is capable of rapid down-regulation in response to a fall in blood pressure. PMID:8937725

Plasma membrane Toll-like receptor activation increases bacterial uptake but abrogates endosomal Lactobacillus acidophilus induction of interferon-β.

PubMed

Boye, Louise; Welsby, Iain; Lund, Lisbeth Drozd; Goriely, Stanislas; Frøkiaer, Hanne

2016-11-01

Lactobacillus acidophilus induces a potent interferon-β (IFN-β) response in dendritic cells (DCs) by a Toll-like receptor 2 (TLR2) -dependent mechanism, in turn leading to strong interleukin-12 (IL-12) production. In the present study, we investigated the involvement of different types of endocytosis in the L. acidophilus-induced IFN-β and IL-12 responses and how TLR2 or TLR4 ligation by lipopolysaccharide and Pam3/4CSK4 influenced endocytosis of L. acidophilus and the induced IFN-β and IL-12 production. Lactobacillus acidophilus was endocytosed by constitutive macropinocytosis taking place in the immature cells as well as by spleen tyrosine kinase (Syk) -dependent phagocytosis but without involvement of plasma membrane TLR2. Stimulation with TLR2 or TLR4 ligands increased macropinocytosis in a Syk-independent manner. As a consequence, incubation of DCs with TLR ligands before incubation with L. acidophilus enhanced the uptake of the bacteria. However, in these experimental conditions, induction of IFN-β and IL-12 was strongly inhibited. As L. acidophilus-induced IFN-β depends on endocytosis and endosomal degradation before signalling and as TLR stimulation from the plasma membrane leading to increased macropinocytosis abrogates IFN-β induction we conclude that plasma membrane TLR stimulation leading to increased macropinocytosis decreases endosomal induction of IFN-β and speculate that this is due to competition between compartments for molecules involved in the signal pathways. In summary, endosomal signalling by L. acidophilus that leads to IFN-β and IL-12 production is inhibited by TLR stimulation from the plasma membrane. © 2016 John Wiley & Sons Ltd.

The Dartmouth Elephant plasma facility

NASA Astrophysics Data System (ADS)

Lynch, K. A.

2017-12-01

The Elephant facility in the Dartmouth Dept of Physics and Astronomyis a 1m by 2m chamber with a microwave-resonant plasma source togetherwith a higher energy electron/ion electrostatic gun. In this chamber weaim to re-create features of the auroral ionosphere including both thethermal plasma background, and the precipitating energetic auroral beam.We can manipulate the position and attitude of various sensors withinthe chamber and monitor their response to the various sources. Recentefforts have focussed on the sheath environment near and around thermalion RPA sensors and the small payloads which carry them into theionosphere.

Plasma Soluble CD163 Level Independently Predicts All-Cause Mortality in HIV-1-Infected Individuals.

PubMed

Knudsen, Troels Bygum; Ertner, Gideon; Petersen, Janne; Møller, Holger Jon; Moestrup, Søren K; Eugen-Olsen, Jesper; Kronborg, Gitte; Benfield, Thomas

2016-10-15

CD163, a monocyte- and macrophage-specific scavenger receptor, is shed as soluble CD163 (sCD163) during the proinflammatory response. Here, we assessed the association between plasma sCD163 levels and progression to AIDS and all-cause mortality among individuals infected with human immunodeficiency virus type 1 (HIV). Plasma sCD163 levels were measured in 933 HIV-infected individuals. Hazard ratios (HRs) with 95% confidence intervals (CIs) associated with mortality were computed by Cox proportional hazards regression. At baseline, 86% were receiving antiretroviral treatment, 73% had plasma a HIV RNA level of <50 copies/mL, and the median CD4(+) T-cell count was 503 cells/µL. During 10.5 years of follow-up, 167 (17.9%) died. Plasma sCD163 levels were higher in nonsurvivors than in survivors (4.92 mg/L [interquartile range {IQR}, 3.29-8.65 mg/L] vs 3.16 mg/L [IQR, 2.16-4.64 mg/L]; P = .0001). The cumulative incidence of death increased with increasing plasma sCD163 levels, corresponding to a 6% or 35% increased risk of death for each milligram per liter or quartile increase, respectively, in baseline plasma sCD163 level (adjusted HR, 1.06 [95% CI, 1.03-1.09] and 1.35 [95% CI, 1.13-1.63], respectively). Plasma sCD163 was an independent marker of all-cause mortality in a cohort of HIV-infected individuals, suggesting that monocyte/macrophage activation may play a role in HIV pathogenesis and be a target of intervention. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Non-Maxwellian and magnetic field effects in complex plasma wakes★

NASA Astrophysics Data System (ADS)

Ludwig, Patrick; Jung, Hendrik; Kählert, Hanno; Joost, Jan-Philip; Greiner, Franko; Moldabekov, Zhandos; Carstensen, Jan; Sundar, Sita; Bonitz, Michael; Piel, Alexander

2018-05-01

In a streaming plasma, negatively charged dust particles create complex charge distributions on the downstream side of the particle, which are responsible for attractive forces between the like-charged particles. This wake phenomenon is studied by means of refined linear response theory and molecular dynamics simulations as well as in experiments. Particular attention is paid to non-Maxwellian velocity distributions that are found in the plasma sheath and to situations with strong magnetic fields, which are becoming increasingly important. Non-Maxwellian distributions and strong magnetic fields result in a substantial damping of the oscillatory wake potential. The interaction force in particle pairs is explored with the phase-resolved resonance method, which demonstrates the non-reciprocity of the interparticle forces in unmagnetized and magnetized systems.

Capillary flow-driven microfluidic device with wettability gradient and sedimentation effects for blood plasma separation.

PubMed

Maria, M Sneha; Rakesh, P E; Chandra, T S; Sen, A K

2017-03-03

We report a capillary flow-driven microfluidic device for blood-plasma separation that comprises a cylindrical well between a pair of bottom and top channels. Exposure of the well to oxygen-plasma creates wettability gradient on its inner surface with its ends hydrophilic and middle portion hydrophobic. Due to capillary action, sample blood self-infuses into bottom channel and rises up the well. Separation of plasma occurs at the hydrophobic patch due to formation of a 'self-built-in filter' and sedimentation. Capillary velocity is predicted using a model and validated using experimental data. Sedimentation of RBCs is explained using modified Steinour's model and correlation between settling velocity and liquid concentration is found. Variation of contact angle on inner surface of the well is characterized and effects of well diameter and height and dilution ratio on plasma separation rate are investigated. With a well of 1.0 mm diameter and 4.0 mm height, 2.0 μl of plasma was obtained (from <10 μl whole blood) in 15 min with a purification efficiency of 99.9%. Detection of glucose was demonstrated with the plasma obtained. Wetting property of channels was maintained by storing in DI water under vacuum and performance of the device was found to be unaffected over three weeks.

Capillary flow-driven microfluidic device with wettability gradient and sedimentation effects for blood plasma separation

PubMed Central

Maria, M. Sneha; Rakesh, P. E.; Chandra, T. S.; Sen, A. K.

2017-01-01

We report a capillary flow-driven microfluidic device for blood-plasma separation that comprises a cylindrical well between a pair of bottom and top channels. Exposure of the well to oxygen-plasma creates wettability gradient on its inner surface with its ends hydrophilic and middle portion hydrophobic. Due to capillary action, sample blood self-infuses into bottom channel and rises up the well. Separation of plasma occurs at the hydrophobic patch due to formation of a ‘self-built-in filter’ and sedimentation. Capillary velocity is predicted using a model and validated using experimental data. Sedimentation of RBCs is explained using modified Steinour’s model and correlation between settling velocity and liquid concentration is found. Variation of contact angle on inner surface of the well is characterized and effects of well diameter and height and dilution ratio on plasma separation rate are investigated. With a well of 1.0 mm diameter and 4.0 mm height, 2.0 μl of plasma was obtained (from <10 μl whole blood) in 15 min with a purification efficiency of 99.9%. Detection of glucose was demonstrated with the plasma obtained. Wetting property of channels was maintained by storing in DI water under vacuum and performance of the device was found to be unaffected over three weeks. PMID:28256564

Hematology and plasma chemistry reference intervals for cultured shortnose sturgeon (Acipenser brevirostrum).

PubMed

Knowles, Susan; Hrubec, Terry C; Smith, Stephen A; Bakal, Robert S

2006-12-01

The shortnose sturgeon, Acipenser brevirostrum, is an imperiled species distributed along the Atlantic coast of North America. Interest in replenishing wild stocks with hatchery-reared fish has created a need for accurate hematologic and biochemical reference intervals to evaluate the health of both fish raised in aquaculture systems and fish in the wild. The objective of this study was to generate hematologic and biochemistry reference intervals for healthy shortnose sturgeon. Blood samples were collected in heparinized tubes from 77 shortnose sturgeon raised in flow-through aquaculture systems. Whole blood and plasma samples were analyzed for hematologic and biochemical variables using standard techniques. Reference intervals were calculated as the central 95% (percentile) of data. Hematologic reference intervals (n = 46) were as follows: PCV 26-46%, hemoglobin 5.7-8.7 g/dL, MCV 307-520 fL, MCH 65.9-107.1 pg, MCHC 15-30 g/dL, plasma proteins (refractometry) 2.8-6.0 g/dL, RBC count 0.65-1.09 x 10(6)/microL, total WBC count 28,376-90,789/microL, small lymphocytes 9063-56,656/microL, large lymphocytes 2122-10,435/microL, neutrophils 3758-33,592/microL, monocytes 0-7137/microL, eosinophils 0-1544/microL, thrombocyte-like cells 6863-23,046/microL, thrombocytes 32,205-122,179/microL, and neutrophil:lymphocyte ratio 0.068-1.026. Plasma chemistry reference intervals (n = 77) were as follows: total protein 2.7-5.3 g/dL, albumin 0.8-1.7 g/dL, globulins 1.8-3.7 mg/dL, creatinine 0-1.4 mg/dL, total bilirubin 0-0.1 mg/dL, alkaline phosphatase 47-497 U/L, aspartate aminotransferase 90-311 U/L, sodium 124-141 mmol/L, potassium 2.9-3.7 mmol/L, chloride 106-121 mmol/L, calcium 6.6-12.1 mg/dL, magnesium 1.6-2.3 mg/dL, phosphorus 5.1-8.1 mg/dL, glucose 37-74 mg/dL, cholesterol 42-133 mg/dL, and osmolality 232-289 mOsm/kg. Reference values reported here will be useful for the early detection, identification, and monitoring of disease and sublethal conditions in cultured shortnose sturgeon.

Laser driven supersonic flow over a compressible foam surface on the Nike lasera)

NASA Astrophysics Data System (ADS)

Harding, E. C.; Drake, R. P.; Aglitskiy, Y.; Plewa, T.; Velikovich, A. L.; Gillespie, R. S.; Weaver, J. L.; Visco, A.; Grosskopf, M. J.; Ditmar, J. R.

2010-05-01

A laser driven millimeter-scale target was used to generate a supersonic shear layer in an attempt to create a Kelvin-Helmholtz (KH) unstable interface in a high-energy-density (HED) plasma. The KH instability is a fundamental fluid instability that remains unexplored in HED plasmas, which are relevant to the inertial confinement fusion and astrophysical environments. In the experiment presented here the Nike laser [S. P. Obenschain et al., Phys. Plasmas 3, 2098 (1996)] was used to create and drive Al plasma over a rippled foam surface. In response to the supersonic Al flow (Mach=2.6±1.1) shocks should form in the Al flow near the perturbations. The experimental data were used to infer the existence and location of these shocks. In addition, the interface perturbations show growth that has possible contributions from both KH and Richtmyer-Meshkov instabilities. Since compressible shear layers exhibit smaller growth, it is important to use the KH growth rate derived from the compressible dispersion relation.

Effects of the herbicide atrazine on Ambystoma tigrinum metamorphosis: duration, larval growth, and hormonal response

USGS Publications Warehouse

Larson, Diane L.; McDonald, Susan; Hamilton, Steven J.; Fivizzani, Albert J.; Newton, Wesley E.

1998-01-01

We exposed larval tiger salamanders (Ambystoma tigrinum) reared in the laboratory from eggs collected from a prairie wetland in North Dakota to three concentrations of atrazine (0, 75, and 250 i??g/L) in a static renewal test to determine the pesticide's effect on (1) plasma corticosterone and thyroxine concentrations, (2) larval size, and (3) days-to-stage at stages 2 and 4 of metamorphic climax. We found significant effects of atrazine on each of these response variables. Plasma thyroxine was elevated in both atrazine-exposed groups compared to the control group; plasma corticosterone was depressed in the 75 i??g/L treatment compared with both the control and 250 i??g/L treatment. Larvae exposed to 75 i??g/L atrazine reached stage 4 later, but at a size and weight comparable to the control group. By contrast, larvae in the 250 i??g/L treatment progressed to stage 4 at the same time but at a smaller size and lower weight than larvae in the control group. These results indicate that the herbicide has the potential to influence tiger salamander life history. We present a model consistent with our results, whereby corticosterone and thyroxine interact to regulate metamorphosis of tiger salamanders based on nutrient assimilation and adult fitness

Interaction of the plasma tail of comet Bradfield 1979L on 1980 February 6 with a possibly flare-generated solar-wind disturbance

NASA Technical Reports Server (NTRS)

Niedner, M. B., Jr.; Brandt, J. C.; Zwickl, R. D.; Bame, S. J.

1983-01-01

Solar-wind plasma data from the ISEE-3 and Helios 2 spacecraft were examined in order to explain a uniquely rapid 10 deg turning of the plasma tail of comet Bradfield 1979l on 1980 February 6. An earlier study conducted before the availability of in situ solar-wind data (Brandt et al., 1980) suggested that the tail position angle change occurred in response to a solar-wind velocity shear across the polar component changed by approximately 50 km/s. The present contribution confirms this result and further suggests that the comet-tail activity was caused by non-corotating, disturbed plasma flows probably associated with an Importance 1B solar flare.

Repeated Exposure to Taekwondo Combat Modulates the Physiological and Hormonal Responses to Subsequent Bouts and Recovery Periods.

PubMed

Bridge, Craig A; Sparks, Andy S; McNaughton, Lars R; Close, Graeme L; Hausen, Matheus; Gurgel, Jonas; Drust, Barry

2018-05-17

Bridge, CA, Sparks, SA, McNaughton, LR, Close, GL, Hausen, M, Gurgel, J, and Drust, B. Repeated exposure to taekwondo combat modulates the physiological and hormonal responses to subsequent bouts and recovery periods. J Strength Cond Res XX(X): 000-000, 2018-This study examined the physiological and hormonal responses to successive taekwondo combats using an ecologically valid competition time structure. Ten elite male international taekwondo competitors (age 19 ± 3 years) took part in a simulated championship event. The competitors performed 4 combats that were interspersed with different recovery intervals (63 ± 4, 31 ± 3 and 156 ± 5 minutes, respectively). Heart rate (HR) was measured during the combats and venous blood samples were obtained both before and after each combat to determine the plasma metabolite and hormone concentrations. The plasma noradrenaline (21.8 ± 12.8 vs. 15.0 ± 7.0 nmol·l) and lactate (13.9 ± 4.2 vs. 10.5 ± 3.2 mmol·l) responses were attenuated (p < 0.05) between combat 1 and 4. Higher (p < 0.05) HR responses were evident in the final combat when compared with the earlier combats. Higher (p < 0.05) resting HR (139 ± 10 vs. 127 ± 12 b·min), plasma lactate (3.1 ± 1.2 vs. 2.0 ± 0.7 mmol·l), glycerol (131 ± 83 vs. 56 ± 38 μmol·l) and nonesterified free fatty acid (0.95 ± 0.29 vs. 0.71 ± 0.28 mmol·l) concentrations were measured before combat 3 compared with combat 1. Repeated exposure to taekwondo combat using an ecologically valid time structure modulates the physiological and hormonal responses to subsequent bouts and recovery periods. Strategies designed to assist competitors to effectively manage the metabolic changes associated with the fight schedule and promote recovery between the bouts may be important during championship events.

Prior Exercise Alters Responses to Hemorrhage

DTIC Science & Technology

2010-07-01

for the swine in our laboratory (4, 17). Plasma renin activ- ity (PRA), aldosterone , cortisol, and adrenocorticotropic hormone (ACTH) were measured...exercise and remained elevated (Table 3). This increase was accompa- nied by elevations in the plasma concentrations of aldosterone and a trend for a... Aldosterone , ng/dL 2.0 T 0.68 12.5* T 3.14 4.2 T 1.59 7.0 T 1.63 PRA, ngAI/mL per h 2.2 T 0.75 1.6 T 0.29 1.9 T 0.40 3.0 T 0.49 Norepinephrine, pg/mL 199 T

Early changes in plasma glucagon and growth hormone response to oral glucose in experimental hyperthyroidism.

PubMed

Tosi, F; Moghetti, P; Castello, R; Negri, C; Bonora, E; Muggeo, M

1996-08-01

The mechanisms underlying deterioration of glucose tolerance associated with hyperthyroidism are not completely understood. Increases in glucagon and growth hormone (GH) secretion have been previously found in hyperthyroid subjects, and could play a crucial role in this phenomenon. However, studies have not yet established the time sequence of changes in plasma glucose on the one hand and glucagon and GH on the other. To assess the early effects of thyroid hormone excess on glucose tolerance and plasma concentrations of the main glucoregulatory hormones, 12 nondiabetic euthyroid subjects underwent an oral glucose tolerance test (OGTT) before and after triiodothyronine ([T3] 120 micrograms/d) was administered for 10 days. Plasma levels of glucose, insulin, glucagon, and GH were determined at fasting and after the glucose load. T3 administration caused a marked increase in serum T3 (8.8 +/- 0.6 v 2.0 +/- 0.1 nmol/L), with clinical and biochemical signs of thyrotoxicosis. During the treatment, plasma glucose significantly increased both at fasting and after the glucose load (basal, 5.3 +/- 0.1 v 4.9 +/- 0.2 mmol/L, P < .05; area under the curve [AUC] for OGTT, 7.7 +/- 0.3 v 6.7 +/- 0.4 mmol/L min, P < .01) without any change in plasma insulin levels. After T3 administration, plasma glucagon levels were lower than at baseline (basal, 92 +/- 7 v 148 +/- 35 ng/L; AUC, 74 +/- 6 v 98 +/- 16 ng/L.min, P < .05), showing an appropriate reduction by the increased glucose levels. Conversely, plasma GH showed impaired suppression by hyperglycemia (AUC, 1.2 +/- 0.3 v 0.7 +/- 0.2 microgram/L.min, P < .05). In conclusion, thyroid hormone excess rapidly impairs glucose tolerance. Altered secretion of GH is an early event in thyrotoxicosis accompanying the onset of hyperglycemia, whereas plasma glucagon is appropriately suppressed by the increased plasma glucose levels. Thus, GH but not glucagon may contribute to the early hyperglycemic effect of thyrotoxicosis.

Metabonomics Approach to Biomarker Discovery, Volume VI: Dose and Time Response of Liver Toxicant

DTIC Science & Technology

2009-05-01

arginine, betaine, creatinine, L-threonine, L-phenylalanine, cytidylic acid , D- pyroglutamic acid , creatine, and 4-guanidinobutyric acid . However, none...Much is known about the systemic response to ANIT exposure, such as the increase in plasma levels of bile acid , cholesterol and phospholipids in...supernanant was transferred to a 5 mm NMR tube. An internal standard consisting of 150 µL of trimethylsilylpropionic (2, 2, 3, 3 d4) acid (TSP

Global power balance on high density field reversed configurations for use in magnetized target fusion

NASA Astrophysics Data System (ADS)

Renneke, Richard M.

Field Reversed Configuration plasmas (FRCs) have been created in the Field Reversed Experiment-Liner (FRX-L) with density 2--6 x 10 22 m-3, total temperature 300--400 eV, and lifetime on the order of 10 micros. This thesis investigates global energy balance on high-density FRCs for the first time. The zero-dimensional approach to global energy balance developed by Rej and Tuszewski (Phys. Fluids 27, p. 1514, 1984) is utilized here. From the shots analyzed with this method, it is clear that energy loss from these FRCs is dominated by particle and thermal (collisional) losses. The percentage of radiative losses versus total loss is an order of magnitude lower than previous FRC experiments. This is reasonable for high density based on empirical scaling from the extensive database of tokamak plasma experiments. Ohmic dissipation, which heats plasma when trapped magnetic field decays to create electric field, is an important source of heating for the plasma. Ohmic heating shows a correlation with increasing the effective Lundquist number (S*). Empirical evidence suggest S* can be increased by lowering the density, which does not achieve the goals of FRX-L. A better way to improve ohmic heating is to trap more poloidal flux. This dissertation shows that FRX-L follows a semi-empirical scaling law which predicts plasma temperature gains for larger poloidal flux. Flux (tauφ) and particle (tauN) lifetimes for these FRCs were typically shorter than 10 micros. Approximately 1/3 of the particle and flux lifetimes for these FRCs did not scale with the usual tauN ≈ tauφ scaling of low-density FRCs, but instead showed tauN ≥ tau φ. However, scatter in the data indicates that the average performance of FRCs on FRX-L yields the typical (for FRCs) relationship tau N ≈ tauφ. Fusion energy gain Q was extrapolated for the shots analyzed in this study using a zero-dimensional scaling code with liner effects. The predicted Q is below the desired value of 0.1 (Schoenberg et al., LA-UR-98-2413, 1998). The situation predicted to lead to Q = 0.1 requires a larger plasma pressure than shown in the present data. This can be accomplished by increasing the plasma density (through larger fill pressure) and maintaining temperature with increased flux trapping. Larger Q and other benefits could be realized by raising the plasma pressure for future FRX-L shots. The innovation inherent in this work performed by the author is the extension of the global power balance model to include a time history of the plasma discharge. This extension required rigorous checking of the power balance model using internal density profiles provided by the multichord interferometer. Typical orders of the parameters calculated by the model are ˜500 MW total loss power, ˜100 MW ohmic heating power, and ˜200 MW total compression (input) power. Radiation was never measured above 5 MW, which is why it was deemed insignificant. It should be noted that these numbers are merely estimates and vary widely between shots.

Toxic plasma concentration of ropivacaine after a paravertebral block in a patient suffering from severe hypoalbuminemia.

PubMed

Calenda, Emile; Baste, Jean Marc; Hajjej, Ridha; Danielou, Eric; Peillon, Christophe

2014-03-01

A case of systemic ropivacaine toxicity from a continuous thoracic paravertebral block in an adult patient who received a lobectomy is presented. The catheter was placed by the surgeon. Eleven hours after the start of the infusion, the patient experienced an arrhythmia leading to death. The total venous plasma concentration of ropivacaine was high (3.2 μg/mL). Furthermore, the patient had severe hypoalbuminemia (albumin 24 g/L), which resulted in the increase of the unbound ropivacaine plasma concentration that was responsible for the toxic side effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Radiosurgery reduces plasma levels of angiogenic factors in brain arteriovenous malformation patients.

PubMed

Xu, Ming; Liu, Xiaoxia; Mei, Guanghai; Zhang, Junjie; Wang, Weixing; Xu, Hongzhi

2018-05-09

Aberrant expression of angiogenic factors has been anecdotally documented in brain arteriovenous malformation (AVM) nidus vessels; however, no data is available on the effect of radiosurgery on the levels of angiogenic factors in AVM patients. We sought to determine the plasma contents of VEGF, TGF-β, Ang-2 and bFGF in 28 brain AVM patients at baseline and post radiosurgery and further analyzed the relationship between plasma contents of these angiogenic factors with clinicopathologic variables of these patients. We enrolled brain AVM patients who underwent Cyberknife radiosurgery at our hospital between January 2014 and December 2015. Brain AVM was confirmed by cerebral angiography and radiosurgery was performed with Cyberknife irradiation. Plasma contents of VEGF, TGF-β, Ang-2 and bFGF were analyzed using commercially available enzyme-linked immunoassay (ELISA) kits. The baseline plasma VEGF content was 222.63 pg/mL (range 43.25-431.25 pg/mL). At three months post surgery, there was a significant -34.29% decline in plasma VEGF content versus baseline (P = 0.000). Furthermore, the median baseline plasma VEGF levels were higher in brain AVM with a nidus volume ≥ 10 cm 3 ) than those with a nidus volume < 10 cm 3 [median(IQR) 293.5 (186.5,359.25) vs. 202 (59.75, 270.75) pg/mL, P = 0.057]. The baseline plasma TGF-β content was 556.17 pg/mL (range 44.44-1486.11 pg/mL) and there was a significant -27.47% decline in plasma TGF-β content at 3 months post radiosurgery versus baseline (P = 0.015). Moreover, the baseline plasma ANG-2 content was 214.27 pg/mL (range 77.14-453.76 pg/mL). There was an immediate and significant -12.47% decline in plasma ANG-2 content post surgery versus baseline (P = 0.002). At three months post surgery, the plasma ANG-2 content still remained significantly depressed versus baseline (P = 0.002). In addition, the baseline plasma bFGF content was 9.17 pg/mL (range 3.67-36.78 pg/mL). No significant difference in plasma bFGF content was observed immediately post surgery and 3 months post surgery versus baseline (P = 0.05). Radiosurgery for brain AVM patients significantly reduced the plasma levels of angiogenic factors. The plasma angiogenic factors may be candidate markers for aberrant agniogenesis of brain AVM and patient response to radiosurgery. Copyright © 2018 Elsevier Inc. All rights reserved.

Erythrocyte concentrations of B1, B2, B6 but not plasma C and E are reliable indicators of nutrition status in the presence of systemic inflammation.

PubMed

Ghashut, Rawia A; McMillan, Donald C; Kinsella, John; Talwar, Dinesh

2017-02-01

There is increasing evidence that the plasma concentration of vitamin D, carotenoids, zinc and selenium are associated with the magnitude of the systemic inflammatory response. In order to examine whether other vitamins may be affected and whether red cell concentrations are less affected by systemic inflammation the aim of the present study was to examine the effect of the systemic inflammatory response on red cell measurements of vitamins B1, B2 and B6, and plasma concentration of vitamin C and E in a large cohort of patients referred for a nutritional screen. Patients referred for nutritional assessment of B1 (n = 551), B2 (n = 251), B6 (n = 313), ascorbic acid (n = 494) and α-tocopherol (n = 395) concentrations. These vitamins were measured using routine laboratory methods. The median concentrations of vitamin B1 grouped according to C-reactive protein concentrations ≤10, 11-80 and >80 mg/L were 543, 664 and 766 ng/g Hb respectively (p < 0.001, 41% higher). The median concentration of vitamin B1 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 547, 664 and 701 ng/g Hb respectively (p < 0.001, 28% higher). The median concentrations of red cell vitamin B2 grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 2.2, 2.3 and 2.4 nmol/g Hb respectively (p < 0.001, 9% higher). The median red cell concentrations of vitamin B2 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 2.1, 2.4 and 2.3 nmol/g Hb respectively (p < 0.001, 14% higher). The median concentrations of red cell vitamin B6 grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 534, 548 and 767 pmol/g Hb respectively (p < 0.001, 44% higher). The median red cell concentrations of vitamin B6 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 462, 644 and 840 pmol/g Hb respectively (p < 0.001, 82% higher). In contrast, the median plasma concentrations of ascorbic acid grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 25.0, 15.0 and 6.0 μmol/l respectively (78% lower, p < 0.001). The median plasma concentrations of ascorbic acid grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 32.0, 13.0 and 5.0 μmol/l respectively (84% lower, p < 0.001). The median α-tocopherol/cholesterol grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 5.9, 4.6 and 2.1 μmol/l respectively (64% lower, p < 0.001). The median α-tocopherol/cholesterol grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 6.0, 5.5 and 2.1 μmol/l respectively (65% lower, p < 0.001). Red cell concentrations of vitamins B1, B2 and B6 were not lower with an increasing systemic inflammatory response. In contrast, plasma concentrations of vitamin C and E were lower. Therefore, compared with plasma concentration, red cell concentrations of B1, B2 and B6 are likely to be more reliable measures of status in the presence of a systemic inflammatory response. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

Particle Acceleration, Magnetic Field Generation in Relativistic Shocks

NASA Technical Reports Server (NTRS)

Nishikawa, Ken-Ichi; Hardee, P.; Hededal, C. B.; Richardson, G.; Sol, H.; Preece, R.; Fishman, G. J.

2005-01-01

Shock acceleration is an ubiquitous phenomenon in astrophysical plasmas. Plasma waves and their associated instabilities (e.g., the Buneman instability, two-streaming instability, and the Weibel instability) created in the shocks are responsible for particle (electron, positron, and ion) acceleration. Using a 3-D relativistic electromagnetic particle (REMP) code, we have investigated particle acceleration associated with a relativistic jet front propagating through an ambient plasma with and without initial magnetic fields. We find only small differences in the results between no ambient and weak ambient parallel magnetic fields. Simulations show that the Weibel instability created in the collisionless shock front accelerates particles perpendicular and parallel to the jet propagation direction. New simulations with an ambient perpendicular magnetic field show the strong interaction between the relativistic jet and the magnetic fields. The magnetic fields are piled up by the jet and the jet electrons are bent, which creates currents and displacement currents. At the nonlinear stage, the magnetic fields are reversed by the current and the reconnection may take place. Due to these dynamics the jet and ambient electron are strongly accelerated in both parallel and perpendicular directions.

Particle Acceleration, Magnetic Field Generation, and Emission in Relativistic Shocks

NASA Technical Reports Server (NTRS)

Nishikawa, Ken-IchiI.; Hededal, C.; Hardee, P.; Richardson, G.; Preece, R.; Sol, H.; Fishman, G.

2004-01-01

Shock acceleration is an ubiquitous phenomenon in astrophysical plasmas. Plasma waves and their associated instabilities (e.g., the Buneman instability, two-streaming instability, and the Weibel instability) created in the shocks are responsible for particle (electron, positron, and ion) acceleration. Using a 3-D relativistic electromagnetic particle (m) code, we have investigated particle acceleration associated with a relativistic jet front propagating through an ambient plasma with and without initial magnetic fields. We find only small differences in the results between no ambient and weak ambient parallel magnetic fields. Simulations show that the Weibel instability created in the collisionless shock front accelerates particles perpendicular and parallel to the jet propagation direction. New simulations with an ambient perpendicular magnetic field show the strong interaction between the relativistic jet and the magnetic fields. The magnetic fields are piled up by the jet and the jet electrons are bent, which creates currents and displacement currents. At the nonlinear stage, the magnetic fields are reversed by the current and the reconnection may take place. Due to these dynamics the jet and ambient electron are strongly accelerated in both parallel and perpendicular directions.

Optimization of microwave-assisted extraction of analgesic and anti-inflammatory drugs from human plasma and urine using response surface experimental designs.

PubMed

Fernández, Purificación; Fernández, Ana M; Bermejo, Ana M; Lorenzo, Rosa A; Carro, Antonia M

2013-04-01

The performance of microwave-assisted extraction and HPLC with photodiode array detection method for determination of six analgesic and anti-inflammatory drugs from plasma and urine, is described, optimized, and validated. Several parameters affecting the extraction technique were optimized using experimental designs. A four-factor (temperature, phosphate buffer pH 4.0 volume, extraction solvent volume, and time) hybrid experimental design was used for extraction optimization in plasma, and three-factor (temperature, extraction solvent volume, and time) Doehlert design was chosen to extraction optimization in urine. The use of desirability functions revealed the optimal extraction conditions as follows: 67°C, 4 mL phosphate buffer pH 4.0, 12 mL of ethyl acetate and 9 min, for plasma and the same volume of buffer and ethyl acetate, 115°C and 4 min for urine. Limits of detection ranged from 4 to 45 ng/mL in plasma and from 8 to 85 ng/mL in urine. The reproducibility evaluated at two concentration levels was less than 6.5% for both specimens. The recoveries were from 89 to 99% for plasma and from 83 to 99% for urine. The proposed method was successfully applied in plasma and urine samples obtained from analgesic users. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Elevated plasma haptoglobin concentrations following parturition are associated with elevated leukocyte responses and decreased subsequent reproductive efficiency in multiparous Holstein dairy cows.

PubMed

Nightingale, Cameron R; Sellers, Matthew D; Ballou, Michael A

2015-03-15

The objectives were to describe the relationship between the intensity of the acute phase response and the metabolic status and leukocyte responses of early postpartum, multiparous cows and determine if subsequent reproductive performance was impaired in cows with a greater acute phase response. Peripheral blood was collected from 240 Holstein cows, 2-8 days in milk and 2nd-8th parity from 8 dairies in Western TX and Eastern NM across 5 days (n=6 cows/dairy/day). Plasma concentrations of haptoglobin were measured and cows were classified as Low (1st quartile), Moderate (2nd and 3rd quartiles), or High (4th quartile) responders. Metabolic measurements included: plasma glucose, urea nitrogen, non-esterified fatty acids and β-hydroxybutyrate concentrations. Leukocyte response measurements included: total leukocyte counts and differentials, neutrophil surface expression of L-selectin, neutrophil oxidative burst capacity when co-cultured with an environmental Escherichia coli, as well as the secretion of tumor necrosis factor-α and interferon-γ when diluted whole blood were co-cultured with lipopolysaccharide and phytohemagglutinin-P, respectively. All data are reported as Low, Moderate, and High haptoglobin responders. Plasma haptoglobin concentrations ranged from below the limit of detection to 8.4 μg/mL, 8.5 to 458 μg/mL, and 459 to 1757 μg/mL. The High cows had more severe neutropenia (3.45, 3.31, and 2.23 ± 0.31 × 10(6)cells/mL; P=0.013) Additionally, the innate leukocyte responses of the High cows were stimulated as evident by increased secretion of tumor necrosis factor-α (568, 565, and 730 ± 73.4 pg/mL; P=0.003), surface expression of L-selectin on neutrophils (70.8, 71.9, and 119.8 ± 7.9 geometric mean fluorescence intensity; P=0.001), and greater neutrophil oxidative burst capacity (37.9, 40.4, and 47.9 ± 0.31 geometric mean fluorescence intensity; P=0.002). In contrast, the secretion of the T-lymphocyte derived cytokine, interferon-γ, was suppressed in both the Moderate and High cows when compared with Low cows (718, 408, and 322 ± 92.2 pg/mL; P=0.01). Haptoglobin class had an overall effect on days to conception (P=0.039). The number of days in milk for 75% of the cows in each haptoglobin class to conceive increased from 123 d in the Low group, 139 d in the Moderate group, and 183 d in the High group. These data indicate that a stronger acute phase response during the early postpartum period that is characterized by an activated innate immune system and a suppressed mitogen-induced interferon-γ secretion resulted in impaired reproductive efficiency, and this response was consistent across the large commercial dairy herds sampled. Copyright © 2015 Elsevier B.V. All rights reserved.

Short-term physiological responses of wild and hatchery-produced red drum during angling

USGS Publications Warehouse

Gallman, E.A.; Isely, J.J.; Tomasso, J.R.; Smith, T.I.J.

1999-01-01

Serum cortisol concentrations, plasma glucose concentrations, plasma lactate concentrations, and plasma osmolalities increased in red drum Sciaenops ocellatus (26.0-65.5 cm total length) during angling in estuarine waters (17-33 g/L salinity, 21-31??C). Angling time varied from as fast as possible (10 s) to the point when fish ceased resisting (up to 350 s). The increases in the physiological characteristics were similar in wild and hatchery-produced fish. This study indicates that hatchery-produced red drum may be used in catch-and-release studies to simulate the responses of wild fish.

Lactobacillus johnsonii Supplementation Attenuates Respiratory Viral Infection via Metabolic Reprogramming and Immune Cell Modulation

PubMed Central

Fonseca, Wendy; Lucey, Kaitlyn; Jang, Sihyug; Fujimura, Kei E.; Rasky, Andrew; Ting, Hung-An; Petersen, Julia; Johnson, Christine C.; Boushey, Homer A.; Zoratti, Edward; Ownby, Dennis R.; Levine, Albert M.; Bobbit, Kevin R.

2017-01-01

Summary Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii-supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii-supplementation reduced airway Th2 cytokines, dendritic cell function, increased T-regulatory cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone-marrow derived dendritic cells (BMDC) from L. johnsonii-supplemented mice had altered cytokine secretion, reduced expression of co-stimulatory molecules, and modified CD4+ T cell cytokines. This was replicated upon co-incubation of wild-type BMDCs with either plasma from L. johnsonii-supplemented mice, or DHA. Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice, or with wild-type derived BMDCs pre-treated with plasma from L. johnsonii-supplemented mice, reduced airway pathologic responses to infection in recipient animals. Thus, L. johnsonii-supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function. PMID:28295020

Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation.

PubMed

Fonseca, W; Lucey, K; Jang, S; Fujimura, K E; Rasky, A; Ting, H-A; Petersen, J; Johnson, C C; Boushey, H A; Zoratti, E; Ownby, D R; Levine, A M; Bobbit, K R; Lynch, S V; Lukacs, N W

2017-11-01

Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone marrow-derived DCs (BMDCs) from L. johnsonii-supplemented mice had altered cytokine secretion, reduced expression of co-stimulatory molecules, and modified CD4+ T-cell cytokines. This was replicated upon co-incubation of wild-type BMDCs with either plasma from L. johnsonii-supplemented mice or DHA. Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice or with wild-type derived BMDCs pretreated with plasma from L. johnsonii-supplemented mice reduced airway pathological responses to infection in recipient animals. Thus L. johnsonii supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function.

Endocrinological Responses to the Administration of Nicotine: Interactions with Drug Initiation, Conditioned Effects, and Conditions of Stress, Volume II

DTIC Science & Technology

1984-01-07

Benowitz, Kuyt and Jacob, 1982; Feyerabend S Russe l l , 1978). 273 10 Measurement of hematocrit was performed as follows: 1) after centrifugation of...Incentives, Washington, D.C.: Winston. Feyerabend , C. , & Russell, M. A. H. (1978). Effect of urinary pH and nicotine excretion rate can plasma...s Feyerabend , c. (1978). Cigarette smoking: A dependence on high-nicotine boll. Drug Metabolism Review, 8_, 29-57. Russell, M. A. H. , Wilson, C

The effect of the systemic inflammatory response on plasma zinc and selenium adjusted for albumin.

PubMed

Ghashut, Rawia A; McMillan, Donald C; Kinsella, John; Vasilaki, Aikaterini T; Talwar, Dinesh; Duncan, Andrew

2016-04-01

The magnitude of systemic inflammatory response, as evidenced by C-reactive protein (CRP), is a major factor associated with lower zinc and selenium. They may also be influenced by their binding proteins, such as albumin. The aim of the present study was to examine the relationships between plasma zinc, selenium and the systemic inflammatory response in a large cohort of patients referred for nutritional screen and also to examine these relationships in patients with critical illness. Patients referred for nutritional assessment of zinc (n = 743) and selenium (n = 833) and 114 patients with critical illness were examined. Intra-assay imprecision was <10% for these analytes. In the nutritional screen cohort, plasma zinc was significantly associated with CRP (rs = -0.404, p < 0.001) and albumin (rs = 0.588, p < 0.001). For each CRP category (≤10, 11-80, >80 mg/l) the zinc/albumin ratio x100 was similar (31, 33 and 32 respectively, p = 0.029). Plasma selenium was significantly associated with CRP (rs = -0.489, p < 0.001) and albumin (rs = 0.600, p < 0.001). With increasing CRP category (≤10, 11-80, >80 mg/l) the selenium/albumin ratio ×100 was lower (2.3, 2.1 and 1.8 respectively, p < 0.001). Similar relationships were also observed in the cohort of patients with critical illness. Plasma zinc was associated with both CRP and albumin. The impact of the systemic inflammatory response could be largely adjusted by albumin concentrations. Plasma selenium was associated with both CRP and albumin. The impact of the systemic inflammatory response on plasma selenium concentrations could not be reasonably adjusted by albumin concentrations. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Dynamic changes in plasma total and high molecular weight adiponectin levels in acute heart failure.

PubMed

Ohara, Takahiro; Hashimura, Kazuhiko; Asakura, Masanori; Ogai, Akiko; Amaki, Makoto; Hasegawa, Takuya; Kanzaki, Hideaki; Sonoda, Mina; Nishizawa, Hitoshi; Funahashi, Tohru; Kitakaze, Masafumi

2011-09-01

Elevated levels of total plasma adiponectin (APN) and high molecular weight (HMW)-APN have been observed in chronic heart failure (HF) and are associated with poor prognosis, however, the response of APN levels in acute HF is not known. The purpose of this study was to clarify the dynamic changes of the plasma total APN, HMW-APN levels, and the ratio of HMW-APN to total APN (HMWR) in acute HF. From February 2006 to January 2007, 20 patients with acute HF (non-ischemic and non-valvular origin, 17 men, aged 63±11 years) were enrolled, and blood was sampled before the onset of the treatment and at discharge. Ten patients admitted for the treatment of supraventricular arrhythmia (8 men, aged 45±13 years) were included as controls. The medians and interquartile ranges of the plasma total APN, HMW-APN levels, and HMWR at admission were 20.8 (14.5-38.9) μg/mL, 12.4 (7.7-23.3) μg/mL, and 0.60 (0.50-0.69), respectively. The total APN and HMW-APN values were significantly higher than the values of the control. The plasma total APN, HMW-APN, and HMWR values at discharge decreased to 19.4 (7.2-27.3)μg/mL, 10.5 (3.2-12.8) μg/mL, and 0.52 (0.46-0.57), respectively. An exploratory survival analysis showed that the higher HMWR values at admission and the larger decrease in HMWR were associated with a better prognosis after discharge. Plasma total APN and HMW-APN values are elevated at the admission for acute HF. Plasma total APN, HMW-APN, and HMWR values decrease following treatment. Higher HMWR at admission and its larger decrease may be the signs of favorable treatment responsiveness in acute HF. Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Effect of Leukocyte-Rich and Platelet-Rich Plasma on Healing of a Horizontal Medial Meniscus Tear in a Rabbit Model

PubMed Central

Shin, Kyun Ho; Lee, Haseok; Kang, Seonghyun; Ko, You-Jin; Lee, Seung-Yup; Park, Jung-Ho; Bae, Ji-Hoon

2015-01-01

There are limited reports on the effect of platelet-rich plasma (PRP) on meniscus healing. The purpose of this study was to investigate the effect of leukocyte-rich PRP (L-PRP) on potential healing of the horizontal medial meniscus tears in a rabbit model. A horizontal medial meniscus tear was created in both knees of nine skeletally mature adult rabbits. Left or right knees were randomly assigned to a L-PRP group, or a control group. 0.5 mL of L-PRP from 10 mL of each rabbit's whole blood was prepared and injected into the horizontal tears in a L-PRP group. None was applied to the horizontal tears in a control group. The histological assessment of meniscus healing was performed at two, four, and six weeks after surgery. We found that there were no significant differences of quantitative histologic scoring between two groups at 2, 4, and 6 weeks after surgery (p > 0.05). This study failed to show the positive effect of single injection of L-PRP on enhancing healing of the horizontal medial meniscus tears in a rabbit model. Single injection of L-PRP into horizontal meniscus tears may not effectively enhance healing of horizontal medial meniscus tears. PMID:26180783

ET AAS evaluation of the stability and pH-sensitivity of, pH-sensitive stealth liposomes containing cisplatin in mouse plasma.

PubMed

Vieira, F P; Mesquita, T L; Lara, P C P; Ramaldes, G A; Beinner, M A; Silva, J B B; Oliveira, M C; Silveira, J N

2013-10-01

In this work, stability and the pH-sensitivity of pH-sensitive stealth liposomes containing cisplatin exposed to plasma medium and their subsequent responses to pH modifications were evaluated. A method to determine platin in mouse plasma by electrothermal atomic absorption spectroscopy (ET AAS) was developed and validated. At first, a comparative study of sample preparation treatments with basic, acidic, and acidic added with Triton X-100 as a modifier was done. The best treatment was obtained with HCl 3% (v/v). The ET AAS method with acid treatment presented linearity at a range of 10-160 ng Pt/mL. The limits of detection (LOD) was 3.1 ng/mL Pt for acid treatment, while the limit quantification (LOQ) was 10 ng/mL Pt. The acid treatment presented good repeatability (VC<15.0%) and recovery close to 100%. This treatment was chosen for subsequent studies due to its best value of repeatability, recovery, LOD and lowest cost. pH-sensitive stealth liposomes, containing cisplatin, demonstrated low stability and poor response to pH variation after plasma incubation. These findings suggest that further studies are needed to improve liposome formulation i.e., to reduce its size. Copyright © 2013 Elsevier B.V. All rights reserved.

Plasma chemerin in young untrained men: association with cardio-metabolic traits and physical performance, and response to intensive interval training.

PubMed

Ouerghi, Nejmeddine; Fradj, Mohamed Kacem Ben; Khammassi, Marwa; Feki, Moncef; Kaabachi, Naziha; Bouassida, Anissa

2017-02-01

Chemerin is an adipose tissue-derived adipokine thought to decrease insulin sensitivity and increase cardiometabolic risk. This study aimed to assess the association of chemerin with cardiometabolic risk and physical performance and examine its response to high-intensity interval training (HIIT). Eighteen young men have been applied a HIIT program during 8 weeks. Plasma chemerin together with several cardiometabolic factors and physical performance indices were determined before and after the training program. Plasma chemerin and insulin were assessed using immunoenzymatic methods. The homeostasis model assessment (HOMA-IR) index was calculated as an estimate of insulin resistance. Basal plasma chemerin was positively correlated with body mass index (r=0.782, p<0.001), body fat (r=0.767, p<0.001), total (r=0.686, p=0.002) and LDL (r=0.587, p=0.010) cholesterol, triglycerides (r=0.775, p<0.001), HOMA-IR (r=0.673, p=0.002) and C-reactive protein (r=0.765, p<0.001). With regards to physical performance, chemerin was negatively correlated with maximal oxygen uptake (r=-0.572, p=0.013) and squat jump (r=-0.627, p=0.005), but positively related to 10-m sprint (r=0.716, p=0.001) and 30-m sprint (r=0.667, p=0.002) times. HIIT program resulted in significant improvements in body composition, plasma lipids and insulin sensitivity. However, no significant change was detected for plasma chemerin in response to HIIT (134±50.7 ng/mL vs. 137±51.9 ng/mL, p=0.750). Basal plasma chemerin is associated with cardiometabolic health and physical performance in young men. Following HIIT, cardiometabolic health and physical performance had improved, but no significant change had occurred for plasma chemerin.

A Cell-Adhesive Plasma Polymerized Allylamine Coating Reduces the In Vivo Inflammatory Response Induced by Ti6Al4V Modified with Plasma Immersion Ion Implantation of Copper

PubMed Central

Walschus, Uwe; Hoene, Andreas; Patrzyk, Maciej; Lucke, Silke; Finke, Birgit; Polak, Martin; Lukowski, Gerold; Bader, Rainer; Zietz, Carmen; Podbielski, Andreas; Nebe, J. Barbara; Schlosser, Michael

2017-01-01

Copper (Cu) could be suitable to create anti-infective implants based on Titanium (Ti), for example by incorporating Cu into the implant surface using plasma immersion ion implantation (Cu-PIII). The cytotoxicity of Cu might be circumvented by an additional cell-adhesive plasma polymerized allylamine film (PPAAm). Thus, this study aimed to examine in vivo local inflammatory reactions for Ti6Al4V implants treated with Cu-PIII (Ti-Cu), alone or with an additional PPAAm film (Ti-Cu-PPAAm), compared to untreated implants (Ti). Successful Cu-PIII and PPAAm treatment was confirmed with X-ray Photoelectron Spectroscopy. Storage of Ti-Cu and Ti-Cu-PPAAm samples in double-distilled water for five days revealed a reduction of Cu release by PPAAm. Subsequently, Ti, Ti-Cu and Ti-Cu-PPAAm samples were simultaneously implanted into the neck musculature of 24 rats. After 7, 14 and 56 days, peri-implant tissue was retrieved from 8 rats/day for morphometric immunohistochemistry of different inflammatory cells. On day 56, Ti-Cu induced significantly stronger reactions compared to Ti (tissue macrophages, antigen-presenting cells, T lymphocytes) and to Ti-Cu-PPAAm (tissue macrophages, T lymphocytes, mast cells). The response for Ti-Cu-PPAAm was comparable with Ti. In conclusion, PPAAm reduced the inflammatory reactions caused by Cu-PIII. Combining both plasma processes could be useful to create antibacterial and tissue compatible Ti-based implants. PMID:28726761

More symptoms but similar blood glucose curve after oral carbohydrate provocation in patients with a history of hypoglycemia-like symptoms compared to asymptomatic patients after Roux-en-Y gastric bypass.

PubMed

Laurenius, Anna; Werling, Malin; Le Roux, Carel W; Fändriks, Lars; Olbers, Torsten

2014-01-01

Laparoscopic Roux-en-Y gastric bypass (LRYGB) is an effective treatment for obesity through altering several physiologic mechanisms. Some patients experience symptoms suggestive of hypglycemia after LRYGB, but whether these symptoms always are associated with low blood glucose are unclear. The objective of this study was to investigate the correlation between symptoms suggestive of hypglycemia, plasma glucose levels and gut hormones involved in glycemic control. Eight LRYGB patients with hypglycemia-like symptoms (SY) and 8 patients with no hypglycemia-like symptoms (ASY) ingested a liquid carbohydrate meal. Insulin, plasma-glucose, glucagon-like peptide 1 (GLP-1) and glucagon were measured intermittently 180 minutes postprandially. In addition, pulse rate, blood pressure and symptoms were assessed. Plasma glucose at 120 min was lower in the ASY mean (95% CI) 2.4 (1.6,3.3) mmol/L (43.2 mg/dL) compared to the SY group 3.0 (3.1,4.6) mmol/L (54.6 mg/dL), (P = .050). The ASY group had larger reduction in plasma glucose than the SY group from pre- to 120 min postmeal -2.2 (-2.8,-1.7) mmol/L (-39.6 mg/dL) versus -1.1 (-1.7,-0.4) mmol/L (-19.8 mg/dL), (P = .011). The concentrations of insulin, GLP-1 and glucagon did not differ significantly between groups. Blood pressure was similar between groups, but the AUC for pulse rate was higher in the SY than ASY group 13009 (11148,14870) versus 11569 (10837,12300) beats/180 minutes, (P = .038). The SY group reported more symptoms than the ASY group, AUC for Sigstad scale 60 to 180 minutes was 970 (-274,1667) for SY versus 170 for ASY (-39,379), (P = .028). Patients with a history of symptoms suggestive of hypglycemia after LRYGB neither demonstrated lower plasma glucose nor greater insulin response compared to asymptomatic patients in response to a liquid carbohydrate meal, but perceived more symptoms. Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

The impact of acute aerobic exercise on chitinase 3-like protein 1 and intelectin-1 expression in obesity

PubMed Central

Slusher, Aaron L; Whitehurst, Michael; Wells, Marie; Maharaj, Arun; Shibata, Yoshimi

2015-01-01

Chitinase 3-like 1 (CHI3L1) and intelectin 1 (ITLN-1) recognize microbial N-acetylglucosamine polymer and galactofuranosyl carbohydrates, respectively. Both lectins are highly abundant in plasma and seem to play pro- and anti-inflammatory roles, respectively, in obesity and inflammatory-related illnesses. The aim of this study was to examine whether plasma levels of these lectins in obese subjects are useful for monitoring inflammatory conditions immediately influenced by acute aerobic exercise. Plasma interleukin-6, a pro-inflammatory cytokine, was also examined. Twenty-two (11 obese and 11 normal-weight) healthy subjects, ages 18–30 years, were recruited to perform a 30 min bout of acute aerobic exercise at 75% VO2max. We confirmed higher baseline levels of plasma CHI3L1, but lower ITLN-1, in obese subjects than in normal-weight subjects. The baseline levels of CHI3L1 were negatively correlated with cardiorespiratory fitness (relative VO2max). However, when controlled for BMI, the relationship between baseline level of CHI3L1 and relative VO2max was no longer observed. While acute aerobic exercise elicited an elevation in these parameters, we found a lower ITLN-1 response in obese subjects compared to normal-weight subjects. Our study clearly indicates that acute aerobic exercise elicits a pro-inflammatory response (e.g. CHI3L1) with a lower anti-inflammatory effect (e.g. ITLN-1) in obese individuals. Furthermore, these lectins could be predictors of outcome of exercise interventions in obesity-associated inflammation. PMID:26316585

Response to fifty grams oral glucose challenge test and pattern of preceding fasting plasma glucose in normal pregnant Nigerians.

PubMed

Adegbola, Omololu; Ajayi, Godwin Olufemi

2014-03-01

Diabetes mellitus in pregnancy has profound implications for the baby and mother and thus active screening for this is desirable. Fifty grams oral glucose challenge test was administered after obtaining consent to 222 women in good health with singleton pregnancies without diabetes mellitus at 24 to 28 weeks gestation after an overnight fast. Venous blood sample was obtained before and 1 hour after the glucose load. A diagnostic 3-hour 100 g oral glucose tolerance test was subsequently performed in all. Two hundred and ten women had a normal response to oral glucose tolerance test i.e. venous plasma glucose below these cut-off levels: fasting 95 mg/dl (5.3 mmol/l), 1 hour 180 mg/dl (10.0 mmol/l), 2 hours 155 mg/dl (8.6 mmol/l) and 3 hours 140 mg/dl (7.8 mmol/l), while 12 were found to have gestational diabetes mellitus and were subsequently excluded from the study. They were appropriately managed. The mean maternal age was 30.9 ± 4.1 years (range 19 to 45 years) and the mean parity was 1.2 ± 1.1 (range 0 to 5). The mean fasting plasma glucose was 74.5 ± 11.5 mg/dl (range 42 to 117 mg/dl), while the mean plasma glucose 1 hour after 50 g glucose challenge test was 115.3 ± 19.1 mg/dl (range 56 to 180 mg/dl). The mean fasting plasma glucose in normal pregnant Nigerians was 74.5 ± 11.5 mg/dl (range 42 to 117 mg/dl). There is a need to re-appraise and possibly review downwards the World Health Organization fasting plasma glucose diagnostic criteria in pregnant Nigerians for better detection of gestational diabetes mellitus. Pregnant women with venous plasma glucose greater than 153.5 mg/dl (8.5 mmol/l) 1 hour after 50 g glucose challenge test are strongly recommended for diagnostic test of gestational diabetes mellitus.

Soluble TRAIL in Normal Pregnancy and Acute Pyelonephritis: a Potential Explanation for the Susceptibility of Pregnant Women to Microbial Products and Infection

PubMed Central

Chaemsaithong, Piya; Romero, Roberto; Korzeniewski, Steven J.; Schwartz, Alyse G.; Stampalija, Tamara; Dong, Zhong; Yeo, Lami; Hernandez-Andrade, Edgar; Hassan, Sonia S; Chaiworapongsa, Tinnakorn

2014-01-01

Objective Pregnancy is characterized by activation of the innate immune response demonstrated by phenotypic and metabolic changes in granulocytes and monocytes. This state of activation has been implicated in the pathophysiology of multiorgan dysfunction of pregnant women with acute viral or bacterial infection. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the mediators responsible for neutrophil apoptosis. Gene deletion of TRAIL results in delayed neutrophil apoptosis and resolution of inflammation after the administration of bacterial endotoxin. The aim of this study was to determine if maternal plasma concentrations of the soluble form of TRAIL (sTRAIL) differ in women with uncomplicated pregnancy and those with acute pyelonephritis. Method A cross-sectional study was conducted to include women in the following groups: 1) non-pregnant (n=23); 2) uncomplicated pregnancies (n=93); and 3) pregnancies with acute pyelonephritis (n=23). Plasma concentrations of sTRAIL were determined by ELISA. Results 1) Women with uncomplicated pregnancies had a lower mean plasma sTRAIL concentration (pg/mL) than non-pregnant women (31.5 ± 10.1 vs. 53.3 ± 12.5; p < 0.001); 2) plasma sTRAIL concentrations did not change as a function of gestational age (Pearson correlation = −0.1; p=0.4); 3) the mean plasma sTRAIL concentration (pg/mL) was significantly lower in pregnant women with acute pyelonephritis than in those with uncomplicated pregnancies (20.5 ± 6.6 vs. 31.5 ± 10.1; p<0.001); and 4) among patients with acute pyelonephritis, patients with bacteremia had a significantly lower mean plasma concentration of sTRAIL (pg/mL) than those without bacteremia (15.1 ± 4.8 vs. 24.7 ± 4.6; p< 0.001). Conclusion Women with uncomplicated pregnancies are associated with a significantly lower mean maternal plasma concentration of sTRAIL than that observed in non-pregnant women. Moreover, a further decrease of plasma sTRAIL concentration was observed in pregnant women with acute pyelonephritis, and this could account, at least in part, for the exaggerated intravascular inflammatory response previously reported in pyelonephritis during pregnancy. PMID:23480056

Single-molecule detection of epidermal growth factor receptor mutations in plasma by microfluidics digital PCR in non-small cell lung cancer patients.

PubMed

Yung, Tony K F; Chan, K C Allen; Mok, Tony S K; Tong, Joanna; To, Ka-Fai; Lo, Y M Dennis

2009-03-15

We aim to develop a digital PCR-based method for the quantitative detection of the two common epidermal growth factor receptor (EGFR) mutations (in-frame deletion at exon 19 and L858R at exon 21) in the plasma and tumor tissues of patients suffering from non-small cell lung cancers. These two mutations account for >85% of clinically important EGFR mutations associated with responsiveness to tyrosine kinase inhibitors. DNA samples were analyzed using a microfluidics system that simultaneously performed 9,180 PCRs at nanoliter scale. A single-mutant DNA molecule in a clinical specimen could be detected and the quantities of mutant and wild-type sequences were precisely determined. Exon 19 deletion and L858R mutation were detectable in 6 (17%) and 9 (26%) of 35 pretreatment plasma samples, respectively. When compared with the sequencing results of the tumor samples, the sensitivity and specificity of plasma EGFR mutation analysis were 92% and 100%, respectively. The plasma concentration of the mutant sequences correlated well with the clinical response. Decreased concentration was observed in all patients with partial or complete clinical remission, whereas persistence of mutation was observed in a patient with cancer progression. In one patient, tyrosine kinase inhibitor was stopped after an initial response and the tumor-associated EGFR mutation reemerged 4 weeks after stopping treatment. The sensitive detection and accurate quantification of low abundance EGFR mutations in tumor tissues and plasma by microfluidics digital PCR would be useful for predicting treatment response, monitoring disease progression and early detection of treatment failure associated with acquired drug resistance.

Differential effects of low and high dose folic acid on endothelial dysfunction in a murine model of mild hyperhomocysteinaemia.

PubMed

Clarke, Zoe L; Moat, Stuart J; Miller, Alastair L; Randall, Michael D; Lewis, Malcolm J; Lang, Derek

2006-12-03

The exact mechanism(s) by which hyperhomocysteinaemia promotes vascular disease remains unclear. Moreover, recent evidence suggests that the beneficial effect of folic acid on endothelial function is independent of homocysteine-lowering. In the present study the effect of a low (400 microg/70 kg/day) and high (5 mg/70 kg/day) dose folic acid supplement on endothelium-dependent relaxation in the isolated perfused mesenteric bed of heterozygous cystathionine beta-synthase deficient mice was investigated. Elevated total plasma homocysteine and impaired relaxation responses to methacholine were observed in heterozygous mice. In the presence of N(G)-nitro-L-arginine methyl ester relaxation responses in wild-type tissues were reduced, but in heterozygous tissues were abolished. Clotrimazole and 18alpha-glycyrrhetinic acid, both inhibitors of non-nitric oxide/non-prostanoid-induced endothelium-dependent relaxation, reduced responses to methacholine in wild-type but not heterozygous tissues. The combination of N(G)-nitro-L-arginine methyl ester and either clotrimazole or 18alpha-glycyrrhetinic acid completely inhibited relaxation responses in wild-type tissues. Both low and high dose folic acid increased plasma folate, reduced total plasma homocysteine and reversed endothelial dysfunction in heterozygous mice. A greater increase in plasma folate in the high dose group was accompanied by a more significant effect on endothelial function. In the presence of N(G)-nitro-L-arginine methyl ester, a significant residual relaxation response was evident in tissues from low and high dose folic acid treated heterozygous mice. These data suggest that the impaired mesenteric relaxation in heterozygous mice is largely due to loss of the non-nitric oxide/non-prostanoid component. While low dose folic acid may restore this response in a homocysteine-dependent manner, the higher dose has an additional effect on nitric oxide-mediated relaxation that would appear to be independent of homocysteine lowering.

Resistance Exercise Attenuates High-Fructose, High-Fat-Induced Postprandial Lipemia

PubMed Central

Wilburn, Jessie R; Bourquin, Jeffrey; Wysong, Andrea; Melby, Christopher L

2015-01-01

INTRODUCTION Meals rich in both fructose and fat are commonly consumed by many Americans, especially young men, which can produce a significant postprandial lipemic response. Increasing evidence suggests that aerobic exercise can attenuate the postprandial increase in plasma triacylglycerols (TAGs) in response to a high-fat or a high-fructose meal. However, it is unknown if resistance exercise can dampen the postprandial lipemic response to a meal rich in both fructose and fat. METHODS Eight apparently healthy men (Mean ± SEM; age = 27 ± 2 years) participated in a crossover study to examine the effects of acute resistance exercise on next-day postprandial lipemia resulting from a high-fructose, high-fat meal. Participants completed three separate two-day conditions in a random order: (1) EX-COMP: a full-body weightlifting workout with the provision of additional kilocalories to compensate for the estimated net energy cost of exercise on day 1, followed by the consumption of a high-fructose, high-fat liquid test meal the next morning (day 2) (~600 kcal) and the determination of the plasma glucose, lactate, insulin, and TAG responses during a six-hour postprandial period; (2) EX-DEF: same condition as EX-COMP but without exercise energy compensation on day 1; and (3) CON: no exercise control. RESULTS The six-hour postprandial plasma insulin and lactate responses did not differ between conditions. However, the postprandial plasma TAG concentrations were 16.5% and 24.4% lower for EX-COMP (551.0 ± 80.5 mg/dL × 360 minutes) and EX-DEF (499.4 ± 73.5 mg/dL × 360 minutes), respectively, compared to CON (660.2 ± 95.0 mg/dL × 360 minutes) (P < 0.05). CONCLUSIONS A single resistance exercise bout, performed ~15 hours prior to a high-fructose, high-fat meal, attenuated the postprandial TAG response, as compared to a no-exercise control condition, in healthy, resistance-trained men. PMID:26508874

Resistance Exercise Attenuates High-Fructose, High-Fat-Induced Postprandial Lipemia.

PubMed

Wilburn, Jessie R; Bourquin, Jeffrey; Wysong, Andrea; Melby, Christopher L

2015-01-01

Meals rich in both fructose and fat are commonly consumed by many Americans, especially young men, which can produce a significant postprandial lipemic response. Increasing evidence suggests that aerobic exercise can attenuate the postprandial increase in plasma triacylglycerols (TAGs) in response to a high-fat or a high-fructose meal. However, it is unknown if resistance exercise can dampen the postprandial lipemic response to a meal rich in both fructose and fat. Eight apparently healthy men (Mean ± SEM; age = 27 ± 2 years) participated in a crossover study to examine the effects of acute resistance exercise on next-day postprandial lipemia resulting from a high-fructose, high-fat meal. Participants completed three separate two-day conditions in a random order: (1) EX-COMP: a full-body weightlifting workout with the provision of additional kilocalories to compensate for the estimated net energy cost of exercise on day 1, followed by the consumption of a high-fructose, high-fat liquid test meal the next morning (day 2) (~600 kcal) and the determination of the plasma glucose, lactate, insulin, and TAG responses during a six-hour postprandial period; (2) EX-DEF: same condition as EX-COMP but without exercise energy compensation on day 1; and (3) CON: no exercise control. The six-hour postprandial plasma insulin and lactate responses did not differ between conditions. However, the postprandial plasma TAG concentrations were 16.5% and 24.4% lower for EX-COMP (551.0 ± 80.5 mg/dL × 360 minutes) and EX-DEF (499.4 ± 73.5 mg/dL × 360 minutes), respectively, compared to CON (660.2 ± 95.0 mg/dL × 360 minutes) (P < 0.05). A single resistance exercise bout, performed ~15 hours prior to a high-fructose, high-fat meal, attenuated the postprandial TAG response, as compared to a no-exercise control condition, in healthy, resistance-trained men.

Energetic particle-driven compressional Alfvén eigenmodes and prospects for ion cyclotron emission studies in fusion plasmas

DOE PAGES

Gorelenkov, N. N.

2016-10-01

As a fundamental plasma oscillation the compressional Alfvén waves (CAW) are interesting for plasma scientists both academically and in applications for fusion plasmas. They are believed to be responsible for the ion cyclotron emission (ICE) observed in many tokamaks. The theory of CAW and ICE was significantly advanced at the end of 20th century in particular motivated by first DT experiments on TFTR and subsequent JET DT experimental studies. More recently, ICE theory was advanced by ST (or spherical torus) experiments with the detailed theoretical and experimental studies of the properties of each instability signal. There the instability responsible formore » ICE signals previously indistinguishable in high aspect ratio tokamaks became the subjects of experimental studies. We discuss further the prospects of ICE theory and its applications for future burning plasma (BP) experiments such as the ITER tokamak-reactor prototype being build in France where neutrons and gamma rays escaping the plasma create extremely challenging conditions for fusion alpha particle diagnostics.a« less

Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-Dopa in parkinsonian monkeys.

PubMed

Grégoire, Laurent; Samadi, Pershia; Graham, Julie; Bédard, Paul J; Bartoszyk, Gerd D; Di Paolo, Thérèse

2009-07-01

Dyskinesia is an important complication of treatment in Parkinson's disease (PD). Sarizotan, a 5-HT(1A) agonist with high affinity for D3 and D4 receptors was investigated on L-Dopa-induced dyskinesia (LID) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of PD. Five MPTP female cynomolgus monkeys (Macaca fascicularis) with a moderate to severe parkinsonian syndrome and LID were used. Sarizotan 0.2, 1, and 2 mg/kg administered alone did not worsen parkinsonian symptoms; there were no effect on locomotor counts or on normal behavior of the monkeys. Sarizotan 0.2, 1, and 2 mg/kg administered 30 min before a fixed dose of L-Dopa (25-30 mg/kg s.c.) + benserazide (50 mg) did not affect the antiparkinsonian response to L-Dopa. However, mean dyskinetic scores were significantly reduced with sarizotan 1 and 2 mg/kg but not at 0.2 mg/kg. Higher doses of sarizotan (4 and 8 mg/kg, administered immediately before L-Dopa) reduced L-Dopa-induced locomotor response in all monkeys. A pharmacokinetic investigation in these monkeys showed a dose-dependent increase in mean plasma sarizotan concentrations with similar mean plasma concentrations for sarizotan 1 mg/kg alone or with L-Dopa, indicating a lack of sarizotan/L-Dopa interaction. The time course of plasma sarizotan concentrations was associated with time of maximal reduction of dyskinesias. When administered daily for two weeks in combination with L-Dopa in the same MPTP monkeys, sarizotan 1 mg/kg had a sustained antidyskinetic effect while maintaining the antiparkinsonian and locomotor effect of L-Dopa. This detailed sarizotan investigation in MPTP monkeys supports the antidyskinetic activity of this drug and for 5-HT(1A) agonists.

Electronegative Low-density Lipoprotein Increases Coronary Artery Disease Risk in Uremia Patients on Maintenance Hemodialysis

PubMed Central

Chang, Chiz-Tzung; Wang, Guei-Jane; Kuo, Chin-Chi; Hsieh, Ju-Yi; Lee, An-Sean; Chang, Chia-Ming; Wang, Chun-Cheng; Shen, Ming-Yi; Huang, Chiu-Ching; Sawamura, Tatsuya; Yang, Chao-Yuh; Stancel, Nicole; Chen, Chu-Huang

2016-01-01

Abstract Electronegative low-density lipoprotein (LDL) is a recognized factor in the pathogenesis of coronary artery disease (CAD) in the general population, but its role in the development of CAD in uremia patients is unknown. L5 is the most electronegative subfraction of LDL isolated from human plasma. In this study, we examined the distribution of L5 (L5%) and its association with CAD risk in uremia patients. The LDL of 39 uremia patients on maintenance hemodialysis and 21 healthy controls was separated into 5 subfractions, L1–L5, with increasing electronegativity. We compared the distribution and composition of plasma L5 between uremia patients and controls, examined the association between plasma L5% and CAD risk in uremia patients, and studied the effects of L5 from uremia patients on endothelial function. Compared to controls, uremia patients had significantly increased L5% (P < 0.001) and L5 that was rich in apolipoprotein C3 and triglycerides. L5% was significantly higher in uremia patients with CAD (n = 10) than in those without CAD (n = 29) (P < 0.05). Independent of other major CAD risk factors, the adjusted odds ratio for CAD was 1.88 per percent increase in plasma L5% (95% CI, 1.01–3.53), with a near-linear dose–response relationship. Compared with controls, uremia patients had decreased flow-mediated vascular dilatation. In ex vivo studies with preconstricted rat thoracic aortic rings, L5 from uremia patients inhibited acetylcholine-induced relaxation. In cultured human endothelial cells, L5 inhibited endothelial nitric oxide synthase activation and induced endothelial dysfunction. Our findings suggest that elevated plasma L5% may induce endothelial dysfunction and play an important role in the increased risk of CAD in uremia patients. PMID:26765403

Bed rest suppresses bioassayable growth hormone release in response to muscle activity

NASA Technical Reports Server (NTRS)

McCall, G. E.; Goulet, C.; Grindeland, R. E.; Hodgson, J. A.; Bigbee, A. J.; Edgerton, V. R.

1997-01-01

Hormonal responses to muscle activity were studied in eight men before (-13 or -12 and -8 or -7 days), during (2 or 3, 8 or 9, and 13 or 14 days) and after (+2 or +3 and +10 or +11 days) 17 days of bed rest. Muscle activity consisted of a series of unilateral isometric plantar flexions, including 4 maximal voluntary contractions (MVCs), 48 contractions at 30% MVC, and 12 contractions at 80% MVC, all performed at a 4:1-s work-to-rest ratio. Blood was collected before and immediately after muscle activity to measure plasma growth hormone by radioimmunoassay (IGH) and by bioassay (BGH) of tibia epiphyseal cartilage growth in hypophysectomized rats. Plasma IGH was unchanged by muscle activity before, during, or after bed rest. Before bed rest, muscle activity increased (P < 0.05) BGH by 66% at -13 or -12 days (2,146 +/- 192 to 3,565 +/- 197 microg/l) and by 92% at -8 or -7 days (2,162 +/- 159 to 4,161 +/- 204 microg/l). After 2 or 3 days of bed rest, there was no response of BGH to the muscle activity, a pattern that persisted through 8 or 9 days of bed rest. However, after 13 or 14 days of bed rest, plasma concentration of BGH was significantly lower after than before muscle activity (2,594 +/- 211 to 2,085 +/- 109 microg/l). After completion of bed rest, muscle activity increased BGH by 31% at 2 or 3 days (1,807 +/- 117 to 2,379 +/- 473 microg/l; P < 0.05), and by 10 or 11 days the BGH response was similar to that before bed rest (1,881 +/- 75 to 4,160 +/- 315 microg/l; P < 0.05). These data demonstrate that the ambulatory state of an individual can have a major impact on the release of BGH, but not IGH, in response to a single bout of muscle activity.

Effects of carbon dioxide exposure on intensively cultured rainbow trout Oncorhynchus mykiss: Physiological responses and fillet attributes

USGS Publications Warehouse

Danley, M.L.; Kenney, P.B.; Mazik, P.M.; Kiser, R.; Hankins, J.A.

2005-01-01

Rainbow trout Oncorhynchus mykiss (261.6 ?? 24.7 g initial weight, mean ?? SEM) at 13.1 ?? 0.2 C were exposed for 94 d to one of three CO2 treatments: control (22.1 ?? 2.8 mg/L), medium (34.5 ?? 3.8 mg/L), or high (48.7 ?? 4.4 mg/L). Trout were checked daily for survival, and fish were sampled at 0, 28, 56, and 84 d for physiological responses, growth, and fillet quality assessments. Trout were also challenged to a 15-min crowding stress at 93 d to assess their ability to initiate a stress response during hypercapnia. Chronically exposed trout showed nearly 100% survival through 84 d exposure (1 of 1,500 fish died). Growth and physiological results showed that increasing elevated CO2 concentrations result in corresponding decreased growth rates and CO2-specific physiological parameters: The medium and high CO2 treatments had significantly slower growth and subsequently smaller fish by 84 d. Exposed trout also showed significantly (P < 0.05) decreased plasma chloride for medium and high CO2 treatments compared to the control from 28 through 84 d. Decreased growth and smaller fish in the medium and high CO2 treatments resulted in correspondingly smaller fresh and smoked fillet weights. Chronic CO2 exposure did not result in notable changes in ultimate muscle pH. Exposure to 15-min crowding stress at 93 d resulted in significant changes in hematocrit, plasma cortisol, glucose, and chloride for all treatment groups. CO2-specific changes were detected in hematocrit, plasma cortisol, and plasma chloride responses following the 15-min crowding stress. ?? Copyright by the World Aquaculture Society 2005.

The influence of platelets, plasma and red blood cells on functional haemostatic assays.

PubMed

Bochsen, Louise; Johansson, Pär I; Kristensen, Annemarie T; Daugaard, Gedske; Ostrowski, Sisse R

2011-04-01

Functional whole blood haemostatic assays are used increasingly to guide transfusion therapy and monitor medical treatment and are also applied for in-vitro evaluations of the haemostatic potential of stored platelets. We investigated how the cellular and plasmatic elements, both isolated and combined, influenced the two methodologically different assays, thrombelastography (TEG) and impedance aggregometry (Multiplate). Platelet-rich plasma (200 × 10/l) or pure plasma (0 platelets), with and without added red blood cells (RBCs), hematocrit 0, 0.15 or 0.29, were produced in vitro from platelet concentrates, fresh frozen plasma and stored RBC. Pure platelets were investigated by removing plasma components from platelet concentrates by diafiltration against the platelet storage solution Intersol. Plasma was readded by diafiltration against plasma in Intersol. Haemostatic function was evaluated by TEG and Multiplate. In the TEG, increasing amounts of RBC reduced clot strength and clot kinetics (α-angle), most markedly in plasma/RBC without platelets. In contrast, RBC in a platelet concentrate matrix enhanced Multiplate aggregation in response to weak agonists (ADP and arachidonic acid). Furthermore, removing plasma from platelet concentrates eliminated the TEG response and diminished the Multiplate aggregation response, but readding plasma to the pure platelet concentrates restored the response. Each of the elements in whole blood, plasma, platelets and RBC, affected the Multiplate and TEG results differently. The results emphasize that the concentrations of all cellular and plasmatic components in whole blood should be taken into account when interpreting results obtained by TEG and multiplate.

Electrically driving large magnetic Reynolds number flows on the Madison plasma dynamo experiment

NASA Astrophysics Data System (ADS)

Weisberg, David; Wallace, John; Peterson, Ethan; Endrezzi, Douglass; Forest, Cary B.; Desangles, Victor

2015-11-01

Electrically-driven plasma flows, predicted to excite a large-scale dynamo instability, have been generated in the Madison plasma dynamo experiment (MPDX), at the Wisconsin Plasma Astrophysics Laboratory. Numerical simulations show that certain topologies of these simply-connected flows may be optimal for creating a plasma dynamo and predict critical thresholds as low as Rmcrit =μ0 σLV = 250 . MPDX plasmas are shown to exceed this critical Rm , generating large (L = 1 . 4 m), warm (Te > 10 eV), unmagnetized (MA > 1) plasmas where Rm < 600 . Plasma flow is driven using ten thermally emissive LaB6 cathodes which generate a J × B torque in Helium plasmas. Detailed Mach probe measurements of plasma velocity for two flow topologies will be presented: edge-localized drive using the multi-cusp boundary field, and volumetric drive using an axial Helmholtz field. Radial velocity profiles show that edge-driven flow is established via ion viscosity but is limited by a volumetric neutral drag force (χ ~ 1 / (ντin)), and measurements of velocity shear compare favorably to Braginskii transport theory. Volumetric flow drive is shown to produce stronger velocity shear, and is characterized by the radial potential gradient as determined by global charge balance.

Modification of saltwater stress response in Cyprinus carpio (Linnaeus, 1758) pre-exposed to pesticide indoxacarb.

PubMed

Ghelichpour, Melika; Taheri Mirghaed, Ali; Mirzargar, Seyed Saeed; Joshaghani, Hamidreza; Ebrahimzadeh Mousavi, Hoseinali

2018-01-01

To evaluate the effects of indoxacarb on saltwater stress response in Cyprinus carpio, the fish were pre-exposed to indoxacarb (0, 0.75, 1.5 and 3mg/L denoted as CP, 0.75IT, 1.5IT and 3IT, respectively) for 21 days and then released to saltwater. A negative control (CN) group was included (the fish were held in indoxacarb-free water for the entire experiment). The fish were sampled immediately (0h) and 24, 48 and 72h after the salinity exposure for the analysis of plasma cortisol, glucose and sodium, chloride, potassium and calcium levels. All fish pre-exposed to 3mg/L indoxacarb, died after the first day of salinity challenge. CP showed typical cortisol response after the salinity challenge, but, cortisol response of the fish pre-exposed to indoxacarb (0.75IT and 1.5IT) was blocked. Plasma glucose increased significantly in all groups compared to the CN; however, this elevation had no consistent trend in 0.75IT and 1.5IT which indicated interference in glucose response due to indoxacarb exposure. Plasma sodium increased (compared to CN) in all groups after the salinity challenge. However, elevation in plasma chloride and potassium was significantly different among the groups and the indoxacarb-treated fish showed slightly sooner ionic disturbance. The results clearly indicate that indoxacarb impairs stress response of C. carpio and the fish may not be able to respond normally to additional stressors, which threatens their survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Pilocarpine disposition and salivary flow responses following intravenous administration to dogs.

PubMed

Weaver, M L; Tanzer, J M; Kramer, P A

1992-08-01

Oral doses of pilocarpine increase salivary flow rates in patients afflicted with xerostomia (dry mouth). This study examined the pharmacokinetics of and a pharmacodynamic response (salivation) to intravenous pilocarpine nitrate administration in dogs. Disposition was linear over a dose range of 225-600 micrograms/kg; plasma concentrations were 10-120 micrograms/L. Elimination was rapid and generally biphasic, with a terminal elimination half-life of approximately 1.3 hr. The systemic clearance of pilocarpine was high (2.22 +/- 0.49 L/kg/hr) and its steady-state volume of distribution (2.30 +/- 0.64 L/kg) was comparable to that of many other basic drugs. All doses of pilocarpine induced measurable submaxillary and parotid salivary flow rates which could be maintained constant over time. Cumulative submaxillary saliva flow was linearly related to total pilocarpine dose. Plasma pilocarpine concentration was linearly related to both steady-state and postinfusion submaxillary salivary flow rates.

Effects of mercuric chloride and sodium selenite on some immune responses of blue gourami, Trichogaster trichopterus (Pallus).

PubMed

Low, K W; Sin, Y M

1998-06-18

The immunotoxicological effects of mercuric chloride and sodium selenite on blue gourami were studied. Some immune responses ranging from non-specific to specific were investigated. These include tissue lysozyme activity, kidney lymphocyte proliferation and plasma agglutinating antibody titre against bacteria. After 2 weeks of chronic exposure, 0.09 mg/l of Hg2+ alone induced a significant increase of kidney lysozyme activity of 4196.3 +/- 1171.0 U/g, but it decreased to 1577.4 +/- 902.4 U/g when exposed simultaneously to equiconcentration of selenium. Plasma lysozyme activity was also increased by co-administration of Hg2+ and SeO3(2-). The level of plasma agglutinating antibody against Aeromonas hydrophila L37 was lowered in the chemical-treated fish. This indicates that the fish immunity was impaired by action of mercury and selenium. However, the in vitro lymphocyte proliferation test shows that mercury concentration lower than 0.045 mg/l Hg2+ enhanced the mitotic rate of kidney lymphocytes by approximately 30%. A high concentration of mercury caused irreversible damaging effects on con A-induced lymphoblastogenesis. In contrast, the inhibitory effect of low concentrations of mercury could be removed by washing. On the other hand, selenium showed a suppressive effect on the lymphocyte proliferation even at 0.5 mg/l.

A facile and selective approach for enrichment of l-cysteine in human plasma sample based on zinc organic polymer: Optimization by response surface methodology.

PubMed

Bahrani, Sonia; Ghaedi, Mehrorang; Ostovan, Abbas; Javadian, Hamedreza; Mansoorkhani, Mohammad Javad Khoshnood; Taghipour, Tahere

2018-02-05

In this research, a facile and selective method was described to extract l-cysteine (l-Cys), an essential α-amino acid for anti-ageing playing an important role in human health, from human blood plasma sample. The importance of this research was the mild and time-consuming synthesis of zinc organic polymer (Zn-MOP) as an adsorbent and evaluation of its ability for efficient enrichment of l-Cys by ultrasound-assisted dispersive micro solid-phase extraction (UA-DMSPE) method. The structure of Zn-MOP was investigated by FT-IR, XRD and SEM. Analysis of variance (ANOVA) was applied for the experimental data to reach the best optimum conditions. The quantification of l-Cys was carried out by high performance liquid chromatography with UV detection set at λ=230nm. The calibration graph showed reasonable linear responses towards l-Cys concentrations in the range of 4.0-1000μg/L (r 2 =0.999) with low limit of detection (0.76μg/L, S/N=3) and RSD≤2.18 (n=3). The results revealed the applicability and high performance of this novel strategy in detecting trace l-Cys by Zn-MOP in complicated matrices. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical implications of basic science discoveries: janus resurrected--two faces of B cell and plasma cell biology.

PubMed

Woodle, E S; Rothstein, D M

2015-01-01

B cells play a complex role in the immune response. In addition to giving rise to plasma cells (PCs) and promoting T cell responses via antigen presentation, they perform immunoregulatory functions. This knowledge has created concerns regarding nonspecific B cell depletional therapy because of the potential to paradoxically augment immune responses. Recent studies now indicate that PCs have immune functions beyond immunoglobulin synthesis. Evidence for a new role for PCs as potent regulatory cells (via IL-10 and IL-35 production) is discussed including the implications for PC-targeted therapies currently being developed for clinical transplantation. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Effect of administration of corticotropin-releasing hormone and glucocorticoid on arginine vasopressin response to osmotic stimulus in normal subjects and patients with hypocorticotropinism without overt diabetes insipidus.

PubMed

Yamada, K; Tamura, Y; Yoshida, S

1989-08-01

We examined the effect of CRH administration on the response of plasma arginine vasopressin (AVP) induced by an osmotic stimulus in six normal subjects and five patients with hypocorticotropinism without overt diabetes insipidus (four patients with Sheehan's syndrome and one with idiopathic pituitary dwarfism with ACTH deficiency). Hypertonic saline infusion (855 mmol/L saline solutions at a rate of 205 mumol/kg.min for 10 min) increased plasma AVP 5.7-fold (P less than 0.01) in normal subjects and 2.4-fold (P less than 0.05) in the patients. CRH administration significantly augmented the plasma AVP response to the osmotic stimulus in the normal subjects, but not in the patients with hypocorticotropinism. CRH administration alone did not influence plasma AVP. These findings suggest that a central CRH-related mechanism(s) was at least partly involved in the augmentation of AVP release. Based on the relatively low plasma AVP response to the osmotic stimulus in patients and their lower plasma AVP levels and higher plasma osmolality under basal conditions, we suggest that patients with hypocorticotropinism have partial diabetes insipidus, in which impairment of central CRH action might be, at least in part, involved. The response of plasma AVP to the osmotic stimulus was attenuated significantly when the patients were given cortisol. Since basal PRA, plasma aldosterone, plasma osmolality, hematocrit, body weight, mean blood pressure, and heart rate were similar with and without cortisol administration, this effect of cortisol may have been due to central suppression of the AVP response to the osmotic stimulus.

The Inner Magnetosphere Plasma Response to Interplanetary Shocks: Van Allen Probes HOPE Observations

NASA Astrophysics Data System (ADS)

Winter, L. M.; Denton, M.; Ferradas, C.; Henderson, M. G.; Larsen, B.; Reeves, G.; Skoug, R. M.; Thomsen, M. F.

2017-12-01

The Van Allen Probes' Helium, Oxygen, Proton, and Electron (HOPE) sensors measure ion and electron populations in the plasmasphere, plasma sheet, and lower-energy ring current, providing unique observations at low energies (0.001-50 keV) and low L-shell (down to 1.5 RE). We use the capabilities of these two spacecraft to probe changes in the low energy particles in response to interplanetary (IP) shocks. We focus on changes in the plasma energies, composition, and pitch angle distributions following IP shocks and storm sudden commencements from 2012-2017 through a comparison of HOPE observations preceding and post shock.

Simultaneous population pharmacokinetic modelling of plasma and intracellular PBMC miltefosine concentrations in New World cutaneous leishmaniasis and exploration of exposure-response relationships.

PubMed

Kip, Anke E; Castro, María Del Mar; Gomez, Maria Adelaida; Cossio, Alexandra; Schellens, Jan H M; Beijnen, Jos H; Saravia, Nancy Gore; Dorlo, Thomas P C

2018-05-10

Leishmania parasites reside within macrophages and the direct target of antileishmanial drugs is therefore intracellular. We aimed to characterize the intracellular PBMC miltefosine kinetics by developing a population pharmacokinetic (PK) model simultaneously describing plasma and intracellular PBMC pharmacokinetics. Furthermore, we explored exposure-response relationships and simulated alternative dosing regimens. A population PK model was developed with NONMEM, based on 339 plasma and 194 PBMC miltefosine concentrations from Colombian cutaneous leishmaniasis patients [29 children (2-12 years old) and 22 adults] receiving 1.8-2.5 mg/kg/day miltefosine for 28 days. A three-compartment model with miltefosine distribution into an intracellular PBMC effect compartment best fitted the data. Intracellular PBMC distribution was described with an intracellular-to-plasma concentration ratio of 2.17 [relative standard error (RSE) 4.9%] and intracellular distribution rate constant of 1.23 day-1 (RSE 14%). In exploring exposure-response relationships, both plasma and intracellular model-based exposure estimates significantly influenced probability of cure. A proposed PK target for the area under the plasma concentration-time curve (day 0-28) of >535 mg·day/L corresponded to >95% probability of cure. In linear dosing simulations, 18.3% of children compared with 2.8% of adults failed to reach 535 mg·day/L. In children, this decreased to 1.8% after allometric dosing simulation. The developed population PK model described the rate and extent of miltefosine distribution from plasma into PBMCs. Miltefosine exposure was significantly related to probability of cure in this cutaneous leishmaniasis patient population. We propose an exploratory PK target, which should be validated in a larger cohort study.

Particle acceleration, magnetic field generation, and emission in relativistic pair jets

NASA Technical Reports Server (NTRS)

Nishikawa, K.-I.; Ramirez-Ruiz, E.; Hardee, P.; Hededal, C.; Kouveliotou, C.; Fishman, G. J.; Mizuno, Y.

2005-01-01

Shock acceleration is a ubiquitous phenomenon in astrophysical plasmas. Recent simulations show that the Weibel instability created by relativistic pair jets is responsible for particle (electron, positron, and ion) acceleration. Using a 3-D relativistic electromagnetic particle (REMP) code, we have investigated particle acceleration associated with a relativistic jet propagating through an ambient plasma with and without initial magnetic fields. The growth rates of the Weibel instability depends on the distribution of pair jets. The Weibel instability created in the collisionless shock accelerates particles perpendicular and parallel to the jet propagation direction. This instability is also responsible for generating and amplifying highly nonuniform, small-scale magnetic fields, which contribute to the electron s transverse deflection behind the jet head. The jitter radiation from deflected electrons has different properties than synchrotron radiation which is calculated in a uniform magnetic field. This jitter radiation may be important to understanding the complex time evolution and/or spectral structure in gamma-ray bursts, relativistic jets, and supernova remnants.

Preparation and surface characterization of plasma-treated and biomolecular-micropatterned polymer substrates

NASA Astrophysics Data System (ADS)

Langowski, Bryan Alfred

A micropatterning process creates distinct microscale domains on substrate surfaces that differ from the surfaces' original chemical/physical properties. Numerous micropatterning methods exist, each having relative advantages and disadvantages in terms of cost, ease, reproducibility, and versatility. Polymeric surfaces micropatterned with biomolecules have many applications, but are specifically utilized in tissue engineering as cell scaffolds that attempt to controlled tissue generation in vivo and ex vivo. As the physical and chemical cues presented by micropatterned substrates control resulting cellular behavior, characterization of these cues via surface-sensitive analytical techniques is essential in developing cell scaffolds that mimic complex in vivo physicochemical environments. The initial focus of this thesis is the chemical and physical characterization of plasma-treated, microcontact-printed (muCP) polymeric substrates used to direct nerve cell behavior. Unmodified and oxygen plasma-treated poly(methyl methacrylate) (PMMA) substrates were analyzed by surface sensitive techniques to monitor plasma-induced chemical and physical modifications. Additionally, protein-micropattern homogeneity and size were microscopically evaluated. Lastly, poly(dimethylsiloxane) (PDMS) stamps and contaminated PMMA substrates were characterized by spectroscopic and microscopic methods to identify a contamination source during microcontact printing. The final focus of this thesis is the development of microscale plasma-initiated patterning (muPIP) as a versatile, reproducible micropatterning method. Using muPIP, polymeric substrates were micropatterned with several biologically relevant inks. Polymeric substrates were characterized following muPIP by surface-sensitive techniques to identify the technique's underlying physical and chemical bases. In addition, neural stem cell response to muPIP-generated laminin micropatterns was microscopically and biologically evaluated. Finally, enhanced versatility of muPIP in generating microscale poly-L-lysine gradients was demonstrated.

Quantification of drugs in plasma without primary reference standards by liquid chromatography-chemiluminescence nitrogen detection: application to tramadol metabolite ratios.

PubMed

Ojanperä, Suvi; Rasanen, Ilpo; Sistonen, Johanna; Pelander, Anna; Vuori, Erkki; Ojanperä, Ilkka

2007-08-01

Lack of availability of reference standards for drug metabolites, newly released drugs, and illicit drugs hinders the analysis of these substances in biologic samples. To counter this problem, an approach is presented here for quantitative drug analysis in plasma without primary reference standards by liquid chromatography-chemiluminescence nitrogen detection (LC-CLND). To demonstrate the feasibility of the method, metabolic ratios of the opioid drug tramadol were determined in the setting of a pharmacogenetic study. Four volunteers were given a single 100-mg oral dose of tramadol, and a blood sample was collected from each subject 1 hour later. Tramadol, O-desmethyltramadol, and nortramadol were determined in plasma by LC-CLND without reference standards and by a gas chromatography-mass spectrometry reference method. In contrast to previous CLND studies lacking an extraction step, a liquid-liquid extraction system was created for 5-mL plasma samples using n-butyl chloride-isopropyl alcohol (98 + 2) at pH 10. Extraction recovery estimation was based on model compounds chosen according to their similar physicochemical characteristics (retention time, pKa, logD). Instrument calibration was performed with a single secondary standard (caffeine) using the equimolar response of the detector to nitrogen. The mean differences between the results of the LC-CLND and gas chromatography-mass spectrometry methods for tramadol, O-desmethyltramadol, and nortramadol were 8%, 32%, and 19%, respectively. The sensitivity of LC-CLND was sufficient for therapeutic concentrations of tramadol and metabolites. A good correlation was obtained between genotype, expressed by the number of functional genes, and the plasma metabolite ratios. This experiment suggests that a recovery-corrected LC-CLND analysis produces sufficiently accurate results to be useful in a clinical context, particularly in instances in which reference standards are not readily accessible.

Perturbative momentum transport in MAST L-mode plasmas

DOE PAGES

Guttenfelder, W.; Field, A. R.; Lupelli, I.; ...

2017-03-28

Non-axisymmetric magnetic fields are used to perturbatively probe momentum transport physics in MAST L-mode plasmas. The low beta L-mode target was chosen to complement previous experiments conducted in high beta NSTX H-mode plasmas (beta N = 3.5-4.6) where an inward momentum pinch was measured. In those cases quasi-linear gyrokinetic simulations of unstable ballooning micro-instabilities predict weak or outward momentum convection, in contrast to the measurements. The weak pinch was predicted to be due to both electromagnetic effects at high beta and low aspect ratio minimizing the symmetry-breaking of the instabilities responsible for momentum transport. In an attempt to lessen thesemore » electromagnetic effects at low aspect ratio, perturbative experiments were run in MAST L-mode discharges at lower beta (beta N = 2). The perturbative transport analysis used the time-dependent response following the termination of applied 3D fields that briefly brake the plasma rotation ( similar to the NSTX H-mode experiments). Assuming time-invariant diffusive (chi(phi))and convective (V-phi) transport coefficients, an inward pinch is inferred with magnitudes, (RV phi/chi(phi)) = (-1)-(-9), similar to those found in NSTX H-modes and in conventional tokamaks. However, if experimental uncertainties due to non-stationary conditions during and after the applied 3D field are considered, a weak pinch or even outward convection is inferred, ( RV phi/chi(phi)) = (-1)-(+5). Linear gyrokinetic simulations indicate that for these lower beta L-modes, the predicted momentum pinch is predicted to be relatively small, ( RV phi/chi(phi))(sim) approximate to -1. While this falls within the experimentally inferred range, the uncertainties are practically too large to quantitatively validate the predictions. Challenges and implications for this particular experimental technique are discussed, as well as additional possible physical mechanisms that may be important in understanding momentum transport in these low aspect ratio plasmas.« less

Perturbative momentum transport in MAST L-mode plasmas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guttenfelder, W.; Field, A. R.; Lupelli, I.

Non-axisymmetric magnetic fields are used to perturbatively probe momentum transport physics in MAST L-mode plasmas. The low beta L-mode target was chosen to complement previous experiments conducted in high beta NSTX H-mode plasmas (beta N = 3.5-4.6) where an inward momentum pinch was measured. In those cases quasi-linear gyrokinetic simulations of unstable ballooning micro-instabilities predict weak or outward momentum convection, in contrast to the measurements. The weak pinch was predicted to be due to both electromagnetic effects at high beta and low aspect ratio minimizing the symmetry-breaking of the instabilities responsible for momentum transport. In an attempt to lessen thesemore » electromagnetic effects at low aspect ratio, perturbative experiments were run in MAST L-mode discharges at lower beta (beta N = 2). The perturbative transport analysis used the time-dependent response following the termination of applied 3D fields that briefly brake the plasma rotation ( similar to the NSTX H-mode experiments). Assuming time-invariant diffusive (chi(phi))and convective (V-phi) transport coefficients, an inward pinch is inferred with magnitudes, (RV phi/chi(phi)) = (-1)-(-9), similar to those found in NSTX H-modes and in conventional tokamaks. However, if experimental uncertainties due to non-stationary conditions during and after the applied 3D field are considered, a weak pinch or even outward convection is inferred, ( RV phi/chi(phi)) = (-1)-(+5). Linear gyrokinetic simulations indicate that for these lower beta L-modes, the predicted momentum pinch is predicted to be relatively small, ( RV phi/chi(phi))(sim) approximate to -1. While this falls within the experimentally inferred range, the uncertainties are practically too large to quantitatively validate the predictions. Challenges and implications for this particular experimental technique are discussed, as well as additional possible physical mechanisms that may be important in understanding momentum transport in these low aspect ratio plasmas.« less

Connective Tissue Growth Factor (CTGF) Expression Modulates Response to High Glucose

PubMed Central

James, Leighton R.; Le, Catherine; Doherty, Heather; Kim, Hyung-Suk; Maeda, Nobuyo

2013-01-01

Connective tissue growth factor (CTGF) is an important mediator of fibrosis; emerging evidence link changes in plasma and urinary CTGF levels to diabetic kidney disease. To further ascertain the role of CTGF in responses to high glucose, we assessed the consequence of 4 months of streptozotocin-induced diabetes in wild type (+/+) and CTGF heterozygous (+/−) mice. Subsequently, we studied the influence of glucose on gene expression and protein in mice embryonic fibroblasts (MEF) cells derived from wildtype and heterozygous mice. At study initiation, plasma glucose, creatinine, triglyceride and cholesterol levels were similar between non-diabetic CTGF+/+ and CTGF+/− mice. In the diabetic state, plasma glucose levels were increased in CTGF+/+ and CTGF+/− mice (28.2 3.3 mmol/L vs 27.0 3.1 mmol/L), plasma triglyceride levels were lower in CTGF+/− mice than in CTGF+/+ (0.7 0.2 mmol/L vs 0.5 0.1 mmol/L, p<0.05), but cholesterol was essentially unchanged in both groups. Plasma creatinine was higher in diabetic CTGF+/+ group (11.7±1.2 vs 7.9±0.6 µmol/L p<0.01), while urinary albumin excretion and mesangial expansion were reduced in diabetic CTGF+/− animals. Cortices from diabetic mice (both CTGF +/+ and CTGF +/−) manifested higher expression of CTGF and thrombospondin 1 (TSP1). Expression of nephrin was reduced in CTGF +/+ animals; this reduction was attenuated in CTGF+/− group. In cultured MEF from CTGF+/+ mice, glucose (25 mM) increased expression of pro-collagens 1, IV and XVIII as well as fibronectin and thrombospondin 1 (TSP1). In contrast, activation of these genes by high glucose was attenuated in CTGF+/− MEF. We conclude that induction of Ctgf mediates expression of extracellular matrix proteins in diabetic kidney. Thus, genetic variability in CTGF expression directly modulates the severity of diabetic nephropathy. PMID:23950936

Plasma iron, C-reactive protein, albumin, and plasma fibrinogen concentrations in dogs with systemic inflammatory response syndrome.

PubMed

Torrente, Carlos; Manzanilla, Edgar G; Bosch, Luis; Fresno, Laura; Rivera Del Alamo, Montserrat; Andaluz, Anna; Saco, Yolanda; Ruiz de Gopegui, Rafael

2015-01-01

To investigate the diagnostic and prognostic value over time of plasma iron compared with the inflammatory markers albumin, C-reactive protein (CRP), and fibrinogen in dogs with systemic inflammatory response syndrome (SIRS). Prospective observational study of sequentially enrolled dogs. ICU of a veterinary teaching hospital. One hundred and sixteen client-owned dogs: 54 dogs with SIRS or sepsis, 42 with focal inflammation, and 20 clinically healthy dogs. Blood samples were obtained on admission in all study groups, and then on alternate days until discharge or death in both inflammation groups. On admission, dogs with SIRS had significantly lower plasma iron (65 ± 5.8 μg/dL, P = 0.001) concentrations than dogs with focal inflammation (89.5 ± 6.2 μg/dL, P = 0.001). Plasma iron, albumin, and CRP effectively discriminated the SIRS/sepsis group from those presenting with focal inflammation with areas under the curve for the receiver operating curves of 0.679, 0.834, and 0.704, respectively. The admission values for these variables did not discriminate survivors from nonsurvivors within the SIRS/sepsis group. However, the magnitude of increase in iron concentration and the decrease in CRP concentration from admission to hospital discharge was higher in survivors than in nonsurvivors within the SIRS/septic group (22.8 vs. 2.51 μg/dL, respectively, P = 0.021 for iron; -67.1 vs. -4.1 mg/L, respectively, P = 0.002 for CRP), resulting in iron and CRP concentrations at hospital discharge for survivors similar to those in the focal inflammation group. Hypoferremia is a sensitive marker of systemic inflammation in dogs. In this study, the increase in iron concentrations during the hospitalization period of SIRS/septic dogs was associated with a better prognosis, suggesting that plasma iron in combination with CRP and albumin concentrations might be used to monitor dogs with inflammatory disease processes. © Veterinary Emergency and Critical Care Society 2015.

The impact of acute aerobic exercise on chitinase 3-like protein 1 and intelectin-1 expression in obesity.

PubMed

Huang, Chun-Jung; Slusher, Aaron L; Whitehurst, Michael; Wells, Marie; Maharaj, Arun; Shibata, Yoshimi

2016-01-01

Chitinase 3-like 1 (CHI3L1) and intelectin 1 (ITLN-1) recognize microbial N-acetylglucosamine polymer and galactofuranosyl carbohydrates, respectively. Both lectins are highly abundant in plasma and seem to play pro- and anti-inflammatory roles, respectively, in obesity and inflammatory-related illnesses. The aim of this study was to examine whether plasma levels of these lectins in obese subjects are useful for monitoring inflammatory conditions immediately influenced by acute aerobic exercise. Plasma interleukin-6, a pro-inflammatory cytokine, was also examined. Twenty-two (11 obese and 11 normal-weight) healthy subjects, ages 18-30 years, were recruited to perform a 30 min bout of acute aerobic exercise at 75% VO2max. We confirmed higher baseline levels of plasma CHI3L1, but lower ITLN-1, in obese subjects than in normal-weight subjects. The baseline levels of CHI3L1 were negatively correlated with cardiorespiratory fitness (relative VO2max). However, when controlled for BMI, the relationship between baseline level of CHI3L1 and relative VO2max was no longer observed. While acute aerobic exercise elicited an elevation in these parameters, we found a lower ITLN-1 response in obese subjects compared to normal-weight subjects. Our study clearly indicates that acute aerobic exercise elicits a pro-inflammatory response (e.g. CHI3L1) with a lower anti-inflammatory effect (e.g. ITLN-1) in obese individuals. Furthermore, these lectins could be predictors of outcome of exercise interventions in obesity-associated inflammation. © 2015 by the Society for Experimental Biology and Medicine.

Laser ablation with applied magnetic field for electric propulsion

NASA Astrophysics Data System (ADS)

Batishcheva, Alla; Batishchev, Oleg; Cambier, Jean-Luc

2012-10-01

Using ultrafast lasers with tera-watt-level power allows efficient ablation and ionization of solid-density materials [1], creating dense and hot (˜100eV) plasma. We propose ablating small droplets in the magnetic nozzle configurations similar to mini-helicon plasma source [2]. Such approach may improve the momentum coupling compared to ablation of solid surfaces and facilitate plasma detachment. Results of 2D modeling of solid wire ablation in the applied magnetic field are presented and discussed. [4pt] [1] O. Batishchev et al, Ultrafast Laser Ablation for Space Propulsion, AIAA technical paper 2008-5294, -16p, 44th JPC, Hartford, 2008.[0pt] [2] O. Batishchev and J.L. Cambier, Experimental Study of the Mini-Helicon Thruster, Air Force Research Laboratory Report, AFRL-RZ-ED-TR-2009-0020, 2009.

Equilibrium drives of the low and high field side n = 2 plasma response and impact on global confinement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paz-Soldan, C.; Logan, N. C.; Haskey, S. R.

The nature of the multi-modal n=2 plasma response and its impact on global confinement is studied as a function of the axisymmetric equilibrium pressure, edge safety factor, collisionality, and L-versus H-mode conditions. Varying the relative phase (ΔΦ UL) between upper and lower in-vessel coils demonstrates that different n=2 poloidal spectra preferentially excite different plasma responses. These different plasma response modes are preferentially detected on the tokamak high-field side (HFS) or low-field side (LFS) midplanes, have different radial extents, couple differently to the resonant surfaces, and have variable impacts on edge stability and global confinement. In all equilibrium conditions studied, themore » observed confinement degradation shares the same ΔΦ UL dependence as the coupling to the resonant surfaces given by both ideal (IPEC) and resistive (MARS-F) MHD computation. Varying the edge safety factor shifts the equilibrium field-line pitch and thus the ΔΦ UL dependence of both the global confinement and the n=2 magnetic response. As edge safety factor is varied, modeling finds that the HFS response (but not the LFS response), the resonant surface coupling, and the edge displacements near the X-point all share the same ΔΦ UL dependence. The LFS response magnitude is strongly sensitive to the core pressure and is insensitive to the collisionality and edge safety factor. This indicates that the LFS measurements are primarily sensitive to a pressure-driven kink-ballooning mode that couples to the core plasma. MHD modeling accurately reproduces these (and indeed all) LFS experimental trends and supports this interpretation. In contrast to the LFS, the HFS magnetic response and correlated global confinement impact is unchanged with plasma pressure, but is strongly reduced in high collisionality conditions in both H- and L-mode. This experimentally suggests the bootstrap current drives the HFS response through the kink-peeling mode drive, though surprisingly weak or no dependence on the bootstrap current is seen in modeling. Instead, modeling is revealed to be very sensitive to the details of the edge current profile and equilibrium truncation. Furthermore, holding truncation fixed, most HFS experimental trends are not captured, thus demonstrating a stark contrast between the robustness of the HFS experimental results and the sensitivity of its computation.« less

Equilibrium drives of the low and high field side n  =  2 plasma response and impact on global confinement

NASA Astrophysics Data System (ADS)

Paz-Soldan, C.; Logan, N. C.; Haskey, S. R.; Nazikian, R.; Strait, E. J.; Chen, X.; Ferraro, N. M.; King, J. D.; Lyons, B. C.; Park, J.-K.

2016-05-01

The nature of the multi-modal n  =  2 plasma response and its impact on global confinement is studied as a function of the axisymmetric equilibrium pressure, edge safety factor, collisionality, and L-versus H-mode conditions. Varying the relative phase (Δ {φ\\text{UL}} ) between upper and lower in-vessel coils demonstrates that different n  =  2 poloidal spectra preferentially excite different plasma responses. These different plasma response modes are preferentially detected on the tokamak high-field side (HFS) or low-field side (LFS) midplanes, have different radial extents, couple differently to the resonant surfaces, and have variable impacts on edge stability and global confinement. In all equilibrium conditions studied, the observed confinement degradation shares the same Δ {φ\\text{UL}} dependence as the coupling to the resonant surfaces given by both ideal (IPEC) and resistive (MARS-F) MHD computation. Varying the edge safety factor shifts the equilibrium field-line pitch and thus the Δ {φ\\text{UL}} dependence of both the global confinement and the n  =  2 magnetic response. As edge safety factor is varied, modeling finds that the HFS response (but not the LFS response), the resonant surface coupling, and the edge displacements near the X-point all share the same Δ {φ\\text{UL}} dependence. The LFS response magnitude is strongly sensitive to the core pressure and is insensitive to the collisionality and edge safety factor. This indicates that the LFS measurements are primarily sensitive to a pressure-driven kink-ballooning mode that couples to the core plasma. MHD modeling accurately reproduces these (and indeed all) LFS experimental trends and supports this interpretation. In contrast to the LFS, the HFS magnetic response and correlated global confinement impact is unchanged with plasma pressure, but is strongly reduced in high collisionality conditions in both H- and L-mode. This experimentally suggests the bootstrap current drives the HFS response through the kink-peeling mode drive, though surprisingly weak or no dependence on the bootstrap current is seen in modeling. Instead, modeling is revealed to be very sensitive to the details of the edge current profile and equilibrium truncation. Holding truncation fixed, most HFS experimental trends are not captured, thus demonstrating a stark contrast between the robustness of the HFS experimental results and the sensitivity of its computation.

Equilibrium drives of the low and high field side n = 2 plasma response and impact on global confinement

DOE PAGES

Paz-Soldan, C.; Logan, N. C.; Haskey, S. R.; ...

2016-03-31

The nature of the multi-modal n=2 plasma response and its impact on global confinement is studied as a function of the axisymmetric equilibrium pressure, edge safety factor, collisionality, and L-versus H-mode conditions. Varying the relative phase (ΔΦ UL) between upper and lower in-vessel coils demonstrates that different n=2 poloidal spectra preferentially excite different plasma responses. These different plasma response modes are preferentially detected on the tokamak high-field side (HFS) or low-field side (LFS) midplanes, have different radial extents, couple differently to the resonant surfaces, and have variable impacts on edge stability and global confinement. In all equilibrium conditions studied, themore » observed confinement degradation shares the same ΔΦ UL dependence as the coupling to the resonant surfaces given by both ideal (IPEC) and resistive (MARS-F) MHD computation. Varying the edge safety factor shifts the equilibrium field-line pitch and thus the ΔΦ UL dependence of both the global confinement and the n=2 magnetic response. As edge safety factor is varied, modeling finds that the HFS response (but not the LFS response), the resonant surface coupling, and the edge displacements near the X-point all share the same ΔΦ UL dependence. The LFS response magnitude is strongly sensitive to the core pressure and is insensitive to the collisionality and edge safety factor. This indicates that the LFS measurements are primarily sensitive to a pressure-driven kink-ballooning mode that couples to the core plasma. MHD modeling accurately reproduces these (and indeed all) LFS experimental trends and supports this interpretation. In contrast to the LFS, the HFS magnetic response and correlated global confinement impact is unchanged with plasma pressure, but is strongly reduced in high collisionality conditions in both H- and L-mode. This experimentally suggests the bootstrap current drives the HFS response through the kink-peeling mode drive, though surprisingly weak or no dependence on the bootstrap current is seen in modeling. Instead, modeling is revealed to be very sensitive to the details of the edge current profile and equilibrium truncation. Furthermore, holding truncation fixed, most HFS experimental trends are not captured, thus demonstrating a stark contrast between the robustness of the HFS experimental results and the sensitivity of its computation.« less

Insulin-Responsive Compartments Containing GLUT4 in 3T3-L1 and CHO Cells: Regulation by Amino Acid Concentrations

PubMed Central

Bogan, Jonathan S.; McKee, Adrienne E.; Lodish, Harvey F.

2001-01-01

In fat and muscle, insulin stimulates glucose uptake by rapidly mobilizing the GLUT4 glucose transporter from a specialized intracellular compartment to the plasma membrane. We describe a method to quantify the relative proportion of GLUT4 at the plasma membrane, using flow cytometry to measure a ratio of fluorescence intensities corresponding to the cell surface and total amounts of a tagged GLUT4 reporter in individual living cells. Using this assay, we demonstrate that both 3T3-L1 and CHO cells contain intracellular compartments from which GLUT4 is rapidly mobilized by insulin and that the initial magnitude and kinetics of redistribution to the plasma membrane are similar in these two cell types when they are cultured identically. Targeting of GLUT4 to a highly insulin-responsive compartment in CHO cells is modulated by culture conditions. In particular, we find that amino acids regulate distribution of GLUT4 to this kinetically defined compartment through a rapamycin-sensitive pathway. Amino acids also modulate the magnitude of insulin-stimulated translocation in 3T3-L1 adipocytes. Our results indicate a novel link between glucose and amino acid metabolism. PMID:11416153

Primaquine in Plasma and Methemoglobinemia in Patients with Malaria Due to Plasmodium vivax in the Brazilian Amazon Basin.

PubMed

Vieira, José Luiz; Ferreira, Michelle E S; Ferreira, Michelle V D; Gomes, Margarete M

2017-05-01

AbstractPrimaquine is the only licensed drug available for the elimination of Plasmodium vivax hypnozoites. Methemoglobinemia is currently reported in the course of treatment. There is evidence that metabolites of primaquine formed by the cytochrome pathway are responsible for methemoglobin formation; a genetic polymorphism of cytochrome isoforms; and a potential influence of gender in the activities of these enzymes requiring the establishment of dose × response curves profiles in different population groups. Concentrations of primaquine in plasma and methemoglobin levels were investigated in 54 patients with malaria due to P. vivax during the course of the standard regimen of chloroquine with primaquine (0.25 mg/kg/day for 14 days). All study subjects lived in an endemic area of the Brazilian Amazon Basin. The blood samples were collected before initiation of treatment and 3 hours (range 2-4 hours) after the administration of antimalarial drugs on days 2, 7, and 14. Plasma primaquine concentrations were similar in both genders (males: range = 164-191 ng/mL, females: range = 193-212 ng/mL). Methemoglobin levels ranged from 3.3% to 5.9% in males and from 3.1% to 6.5% in females. There were no significant correlations between the plasma primaquine concentrations or total dose and methemoglobin levels, suggesting that unidentified metabolites rather than parent drug were likely responsible for changes in methemoglobin levels. There was no significant influence of gender on primaquine concentrations in plasma or methemoglobin levels.

The inhibitory effect of milk on the absorption of dietary phenolic acids and the change in human plasma antioxidant capacity through a mechanism involving both milk proteins and fats.

PubMed

Zhang, Hao; Jiang, Lu; Guo, Huiyuan; Sun, Jing; Liu, Xianting; Liu, Ruihai; Ding, Qingbo; Ren, Fazheng

2013-07-01

We assessed the effects of milk proteins and fats, alone and in combination, on the absorption of phenolic acids and the change in plasma antioxidant capacity after jujube juice intake in humans. Twenty volunteers received the following four treatments each in a 4 × 4 Latin square design with a minimum 1 week interval: 200 mL of jujube juice plus 200 mL of (1) water; (2) whole milk; (3) skimmed milk; or (4) milk fat. The results showed that skimmed milk extended the time to reach maximum increase of plasma phenolic acids concentrations and plasma antioxidant capacity. However, neither the skimmed milk nor the milk fat had a significant effect on the absorption of phenolic acids. In contrast, whole milk significantly reduced the absorption of phenolic acids and the increase in plasma antioxidant capacity (p < 0.05). In vitro results suggested the formation of complexes during digestion that involved milk proteins, milk fats, and phenolic acids, which were responsible for the inhibitory effect of whole milk. Milk proteins and fats together, but not alone, are responsible for the inhibitory effect of milk on the absorption of phenolic acids and the change in plasma antioxidant capacity. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Viremic HIV Infected Individuals with High CD4 T Cells and Functional Envelope Proteins Show Anti-gp41 Antibodies with Unique Specificity and Function

PubMed Central

Curriu, Marta; Fausther-Bovendo, Hughes; Pernas, María; Massanella, Marta; Carrillo, Jorge; Cabrera, Cecilia; López-Galíndez, Cecilio; Clotet, Bonaventura; Debré, Patrice; Vieillard, Vincent; Blanco, Julià

2012-01-01

Background CD4 T-cell decay is variable among HIV-infected individuals. In exceptional cases, CD4 T-cell counts remain stable despite high plasma viremia. HIV envelope glycoprotein (Env) properties, namely tropism, fusion or the ability to induce the NK ligand NKp44L, or host factors that modulate Env cytopathic mechanisms may be modified in such situation. Methods We identified untreated HIV-infected individuals showing non-cytopathic replication (VL>10,000 copies/mL and CD4 T-cell decay<50 cells/µL/year, Viremic Non Progressors, VNP) or rapid progression (CD4 T-cells<350 cells/µL within three years post-infection, RP). We isolated full-length Env clones and analyzed their functions (tropism, fusion activity and capacity to induce NKp44L expression on CD4 cells). Anti-Env humoral responses were also analyzed. Results Env clones isolated from VNP or RP individuals showed no major phenotypic differences. The percentage of functional clones was similar in both groups. All clones tested were CCR5-tropic and showed comparable expression and fusogenic activity. Moreover, no differences were observed in their capacity to induce NKp44L expression on CD4 T cells from healthy donors through the 3S epitope of gp41. In contrast, anti- Env antibodies showed clear functional differences: plasma from VNPs had significantly higher capacity than RPs to block NKp44L induction by autologous viruses. Consistently, CD4 T-cells isolated from VNPs showed undetectable NKp44L expression and specific antibodies against a variable region flanking the highly conserved 3S epitope were identified in plasma samples from these patients. Conversely, despite continuous antigen stimulation, VNPs were unable to mount a broad neutralizing response against HIV. Conclusions Env functions (fusion and induction of NKp44L) were similar in viremic patients with slow or rapid progression to AIDS. However, differences in humoral responses against gp41 epitopes nearby 3S sequence may contribute to the lack of CD4 T cell decay in VNPs by blocking the induction of NKp44L by gp41. PMID:22312424

The influence of inflammation on plasma zinc concentration in apparently healthy, HIV+ Kenyan adults and zinc responses after a multi-micronutrient supplement.

PubMed

Mburu, A S W; Thurnham, D I; Mwaniki, D L; Muniu, E M; Alumasa, F M

2010-05-01

Plasma zinc is an important biomarker of zinc status, but the concentration is depressed by inflammation. Apparently healthy adults, who tested positive twice for human immunodeficiency virus (HIV) but who had not reached stage IV or clinical AIDS, were randomly allocated to receive a food supplement (n=17 and 21) or the food plus a micronutrient capsule (MN; n=10 men and n=33 women) containing 15 mg zinc/day. We used the inflammation biomarkers, C-reactive protein (CRP) and alpha1-acid glycoprotein (AGP), to identify subjects with and without inflammation and determine the effect of inflammation on the response of plasma zinc concentrations to the MN and food supplements. There were no differences between men and women either in plasma zinc or in the responses to the supplements and their data were combined. Plasma zinc was lower in those with inflammation than without. Repeated measures analysis of variance (ANOVA) showed that inflammation blocked increases in plasma zinc, and there was an approximate 10% increase in plasma zinc concentration in response to the MN supplement (P=0.023) in those without inflammation. Subgroup analysis showed mean changes in plasma zinc of 0.95 and -0.83 micromol/l (P=0.031) in response to the MN and food treatments, respectively, in those without inflammation at both time points. Inflammation seems to block any increase in plasma zinc after MN supplement and it is important to identify those without inflammation to determine the effectiveness of a zinc supplementation program.

Biocompatibility of modified ultra-high-molecular-weight polyethylene

NASA Astrophysics Data System (ADS)

Novotná, Z.; Lacmanová, V.; Rimpelová, S.; Juřik, P.; Polívková, M.; Å vorčik, V.

2016-09-01

Ultra-high-molecular-weight polyethylene (UHMWPE, PE) is a synthetic polymer used for biomedical applications because of its high impact resistance, ductility and stability in contact with physiological fluids. Therefore this material is being used in human orthopedic implants such as total joint replacements. Surface modification of this material relates to changes of its surface hydrophilicity, energy, microstructure, roughness, and morphology, all influencing its biological response. In our recent work, PE was treated by an Ar+ plasma discharge and then grafted with biologically active polyethylene glycol in order to enhance adhesion and proliferation of mouse fibroblast (L929). The surface properties of pristine PE and its grafted counterparts were studied by goniometry (surface wettability). Furthermore, Atomic Force Microscopy was used to determine the surface morphology and roughness. The biological response of the L929 cell lines seeded on untreated and plasma treated PE matrices was quantified in terms of the cell adhesion, density, and metabolic activity. Plasma treatment leads to the ablation of the polymer surface layers. Plasma treatment and subsequent poly(ethylene glycol) grafting lead to dramatic changes in the polymer surface morphology and roughness. Biological tests, performed in vitro, show increased adhesion and proliferation of cells on modified polymers. Grafting with poly(ethylene glycol) increases cell proliferation compared to plasma treatment.

Modeling of non-stationary local response on impurity penetration in plasma

NASA Astrophysics Data System (ADS)

Tokar, M. Z.; Koltunov, M.

2012-04-01

In fusion devices, strongly localized intensive sources of impurities may arise unexpectedly, e.g., if the wall is excessively demolished by hot plasma particles, or can be created deliberately through impurity seeding. The spreading of impurities from such sources both along and perpendicular to the magnetic field is affected by coulomb collisions with background particles, ionization, acceleration by electric field, etc. Simultaneously, the plasma itself can be significantly disturbed by these interactions. To describe self-consistently the impurity spreading process and the plasma response, three-dimensional fluid equations for the particle, parallel momentum, and energy balances of various plasma components are solved by reducing them to ordinary differential equations for the time evolution of several parameters characterizing the solutions in principal details: the maximum densities of impurity ions of different charges, the dimensions both along and across the magnetic field of the shells occupied by these particles, the characteristic temperatures of all plasma components, and the densities of the main ions and electrons in different shells. The results of modeling for penetration of lithium singly charged particles in tokamak edge plasma are presented. A new mechanism for the condensation phenomenon and formation of cold dense plasma structures, implying an outstanding role of coulomb collisions between main and impurity ions, is proposed.

Two-Dimensional Transport Studies for the Composition and Structure of the Io Plasma Torus

NASA Technical Reports Server (NTRS)

Smyth, William H.

2003-01-01

The overall objective of this project is to investigate the roles of local and spatially extended plasma sources created by Io, plasma torus chemistry, and plasma convective and diffusive transport in producing the long-lived S(+), S(++) and O(+) radial ribbon structures of the plasma torus, their System III longitude and local-time asymmetries, their energy sources and their possible time variability. To accomplish this objective, two-dimensional [radial (L) and System III longitude] plasma transport equations for the flux-tube plasma content and energy content will be solved that include the convective motions for both the east-west electric field and co-rotational velocity-lag profile near Io s orbit, radial diffusion, and the spacetime dependent flux-tube production and loss created by both neutral-plasma and plasma-ion reaction chemistry in the plasma torus. For neutral-plasma chemistry, the project will for the first time undertake the calculation of realistic three-dimensional, spatially-extended, and time-varying contributions to the flux-tube ion-production and loss that are produced by Io's corona and extended neutral clouds. The unknown two-dimensional spatial nature of diffusion in the plasma transport will be isolated and better defined in the investigation by the collective consideration of the foregoing different physical processes. For energy transport, the energy flow from hot pickup ions (and a new electron source) to thermal ions and electrons will be included in investigating the System III longitude and local-time temperature asymmetries in the plasma torus. The research is central to the scope of the NASA Sun-Earth Connection Roadmap in Quest II Campaign 4 "Comparative Planetary Space Environments" by addressing key questions for understanding the magnetosphere of planets with high rotation rates and large internal plasma sources and, in addition, is of considerable importance to the NASA Solar System Exploration Science Theme. In this regard, Jupiter is the most extreme example with its rapid rotation and with its inner Galilean satellite Io providing the dominant plasma source for the magnetosphere.

Respiratory compensation to a primary metabolic alkalosis in humans.

PubMed

Feldman, Mark; Alvarez, Naiara M; Trevino, Michael; Weinstein, Gary L

2012-11-01

There is limited and disparate information about the extent of the respiratory compensation (hypoventilation) that occurs in response to a primary metabolic alkalosis in humans. Our aim was to examine the influence of the plasma bicarbonate concentration, the plasma base excess, and the arterial pH on the arterial carbon dioxide tension in 52 adult patients with primary metabolic alkalosis, mostly due to diuretic use or vomiting. Linear regression analysis was used to correlate degrees of alkalosis with arterial carbon dioxide tensions. In this alkalotic cohort, whose arterial plasma bicarbonate averaged 31.6 mEq/l, plasma base excess averaged 7.8 mEq/l, and pH averaged 7.48, both plasma bicarbonate and base excess correlated closely with arterial carbon dioxide tensions (r = 0.97 and 0.96, respectively; p < 0.0001), while there was little relationship between arterial pH and arterial carbon dioxide tensions (p = 0.08). The arterial carbon dioxide tension increased 1.2 torr for each 1.0 mEq/l increment in plasma bicarbonate or base excess (95% confidence interval, 1.1 - 1.3 torr). This 1.2 torr increase amounts to a ~ 50% greater degree of respiratory compensation (hypoventilation) to primary metabolic alkalosis than has been reported in prior smaller studies.

Optimal vitamin D plasma levels are associated with lower bacterial DNA translocation in HIV/hepatitis c virus coinfected patients.

PubMed

García-Álvarez, Mónica; Berenguer, Juan; Jiménez-Sousa, Maria Ángeles; Vázquez-Morón, Sonia; Carrero, Ana; Gutiérrez-Rivas, Mónica; Aldámiz-Echevarría, Teresa; López, Juan Carlos; García-Broncano, Pilar; Resino, Salvador

2016-04-24

Vitamin D has been linked to the immune response modulation and the integrity of the intestinal mucosal barrier. Therefore, vitamin D might be involved in bacterial translocation related to HIV infection. Our major aim was to analyze the association between plasma levels of 25-hydroxy-vitamin D [25(OH)D] and bacterial 16S ribosomal DNA (bactDNA) in 120 HIV/hepatitis c virus (HCV) coinfected patients. Cross-sectional study. Plasma 25(OH)D levels were quantified by enzyme immunoassay. The vitamin D status was defined as deficient (<25 nmol/l), insufficient (25-74 nmol/l), and optimal (≥75 nmol/l) plasma levels. Plasma bactDNA levels were measured by quantitative real-time PCR. For bactDNA levels the cutoffs used were as follows: low [p75th). Eighteen (15%) patients had 25(OH)D deficiency, 93 (77.5%) had insufficiency and nine (7.5%) had 25(OH)D optimal values. The bactDNA levels were lower in patients with 25(OH)D at least 75 nmol/l [37 copies/μl] than in patients with 25(OH)D insufficiency [84.2 copies/μl; P = 0.042]. Conversely, low bactDNA levels (

Long-term, low-dose, intravenous vitamin C leads to plasma calcium oxalate supersaturation in hemodialysis patients.

PubMed

Canavese, Caterina; Petrarulo, Michele; Massarenti, Paola; Berutti, Silvia; Fenoglio, Roberta; Pauletto, Daniela; Lanfranco, Giacomo; Bergamo, Daniela; Sandri, Luisa; Marangella, Martino

2005-03-01

Ascorbate supplementation for patients on regular dialysis treatment (RDT) is advised to obviate deficiency and improve epoetin response in those with functional iron deficiency. However, clear-cut safety concerns regarding hyperoxalemia are still poorly understood. This study tries to establish safety/efficacy profiles of ascorbate and oxalate during long-term intravenous ascorbate supplementation. A prospective study was performed in 30 patients on RDT showing ascorbate deficiency (plasma ascorbate < 2.6 mg/L [<15 micromol/L]): 18 patients were administered intravenous ascorbate during 18 months (250 mg/wk, subsequently increased to 500 mg), and 12 patients were taken as reference untreated cases. Plasma ascorbate and oxalate assays and dialytic balance determinations were performed (ion chromatography and reverse-phase high-performance liquid chromatography, respectively) at baseline, during treatment, and 12 months after withdrawal. Plasma ascorbate levels increased dose dependently with supplementation (1.6 +/- 0.8 mg/L [9.1 +/- 4.6 mumol/L] at baseline, 2.8 +/- 1.8 mg/L [15.9 +/- 10.1 micromol/L]) with 250 mg of ascorbate, and 6.6 +/- 2.8 mg/L [37.5 +/- 16.0 micromol/L] with 500 mg/wk of ascorbate), but only normalized with greater dosages for several months in 94% of patients. Baseline plasma oxalate levels increased from 3.2 +/- 0.8 mg/L (35.8 +/- 8.8 micromol/L) to 3.6 +/- 0.8 mg/L (39.5 +/- 9.1 micromol/L) and 4.5 +/- 0.9 mg/L (50.3 +/- 10.4 micromol/L) with 250 and 500 mg, respectively ( P < 0.001). The calcium oxalate saturation threshold was exceeded by 7 of 18 patients (40%) during 6 months therapy with 500 mg/wk. Ascorbate dialysis removal increased from 37.8 +/- 23.2 mg (215 +/- 132 micromol) to 99.6 +/- 51.7 mg (566 +/- 294 micromol) during supplementation (P < 0.001), with corresponding increases in oxalate removal from 82.5 +/- 33.2 mg (917 +/- 369 micromol) to 111.2 +/- 32.6 mg/L (1,236 +/- 362 micromol; P < 0.01). Withdrawal reverted plasma levels and dialysis removal to initial values. Values for untreated patients did not change during 1 year of follow-up. Patients on RDT may resolve ascorbate deficiency with intravenous supplementation of 500 mg/wk, but this implies a significant risk for oxalate supersaturation. Oxalate measurements are strongly recommended during long-term ascorbate therapy.

Effects of short-chain fructo-oligosaccharides on glucose and lipid metabolism in mild hypercholesterolaemic individuals.

PubMed

Giacco, R; Clemente, G; Luongo, D; Lasorella, G; Fiume, I; Brouns, F; Bornet, F; Patti, L; Cipriano, P; Rivellese, A A; Riccardi, G

2004-06-01

The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism. To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia. A randomized double-blind sequential cross-over study. Thirty subjects of both genders (20 M/10 F), mean age 45.5+/-9.9 years (M+/-SD), BMI 26.6+/-2.2 kg/m(2), with plasma cholesterol >5.17 and <7.76 mmol/l and plasma triglycerides <3.45 mmol/l, participated in the study. The study was performed after a wash-out period of 1 month and a run-in period of 1 month to stabilize patients on a standard diet (CHO 50%, fat 30%, protein 20%, fibre 20 g/day) plus placebo (maltodextrine plus aspartame 15 g/day). At the end of run-in, subjects were randomly assigned to receive sc-FOS (Actilight) (10.6g/day) or placebo (maltodextrine plus aspartame 15 g/day) with tea and/or coffee for a duration of 2 months and thereafter switched to the other treatment for additional 2 months. Plasma glucose, total and lipoprotein (VLDL, LDL, HDL) cholesterol and triglyceride concentrations were measured in the fasting state at the end of run-in and of each treatment period. At the end of the two treatment periods, patients consumed a standard test meal (protein 15%, carbohydrate 34%, fat 51%, kJ 3988) 1h after the administration of 5.3g of sc-FOS or placebo; plasma glucose, insulin, free fatty acid (FFA) and triglyceride responses to the test meal were evaluated. No significant difference in fasting parameters was detected between the two treatments. After sc-FOS and placebo plasma cholesterol levels were, respectively, 6.47+/-0.70 and 6.44+/-0.78 mmol/l (n.s.) and plasma triglycerides were 1.53+/-0.71 and 1.56+/-0.53 mmol/l (n.s.). No significant differences were observed in cholesterol and triglyceride content of VLDL, LDL and HDL and in plasma Apo A1 levels; conversely, fasting plasma Lp(a) concentrations were significantly increased after sc-FOS (37+/-38 vs. 33+/-35 mg/dl; P<0.005). Postprandial responses of glucose, FFA and triglycerides were not significantly different between sc-FOS and placebo, while postprandial insulin response (incremental area) was significantly reduced after sc-FOS compared to placebo (14,490+/-7416 vs. 17,760+/-7710 pmol/l x 300 min; P<0.02). A moderate intake of sc-FOS has no major effects on lipid metabolism, both in the fasting and in the postprandial period, in individuals with mild hypercholesterolaemia. A small but significant increase of Lp(a) concentrations was observed with sc-FOS consumption together with a reduction of the postprandial insulin response; however, the clinical relevance of these small effects is unclear.

Using the developed cross-flow filtration chip for collecting blood plasma under high flow rate condition and applying the immunoglobulin E detection

NASA Astrophysics Data System (ADS)

Yeh, Chia-Hsien; Hung, Chia-Wei; Wu, Chun-Han; Lin, Yu-Cheng

2014-09-01

This paper presents a cross-flow filtration chip for separating blood cells (white blood cells, red blood cells, and platelets) and obtaining blood plasma from human blood. Our strategy is to flow the sample solution in parallel to the membrane, which can generate a parallel shear stress to remove the clogging microparticles on the membrane, so the pure sample solution is obtained in the reservoir. The cross-flow filtration chip includes a cross-flow layer, a Ni-Pd alloy micro-porous membrane, and a reservoir layer. The three layers are packaged in a polymethylmethacrylate (PMMA) frame to create the cross-flow filtration chip. Various dilutions of the blood sample (original, 2 × , 3 × , 5 × , and 10×), pore sizes with different diameters (1 µm, 2 µm, 4 µm, 7 µm, and 10 µm), and different flow rates (1 mL/min, 3 mL/min, 5 mL/min, 7 mL/min, and 10 mL/min) are tested to determine their effects on filtration percentage. The best filtration percentage is 96.2% when the dilution of the blood sample is 10 × , the diameter of pore size of a Ni-Pd alloy micro-porous membrane is 2 µm, and the flow rate is 10 mL/min. Finally, for the clinical tests of the immunoglobulin E (IgE) concentration, the cross-flow filtration chip is used to filter the blood of the allergy patients to obtain the blood plasma. This filtered blood plasma is compared with that obtained using the conventional centrifugation based on the enzyme-linked immunosorbent assay. The results reveal that these two blood separation methods have similar detection trends. The proposed filtration chip has the advantages of low cost, short filtration time, and easy operation and thus can be applied to the separation of microparticles, cells, bacteria, and blood.

Peptide YY in diabetics treated chronically with an intestinal glucosidase inhibitor.

PubMed

Füessl, H S; Adrian, T E; Uttenthal, L O; Bloom, S R

1988-10-03

Peptide YY (PYY) is a recently discovered peptide found in the distal ileum and colon. It circulates in plasma and concentrations rise in malabsorptive conditions. The potential of PYY as an indicator of impaired carbohydrate digestion was studied in a pharmacological model of intestinal glucosidase inhibition. Thirteen type-2 diabetics on long-term treatment with the alpha-glucosidase inhibitor acarbose (3 x 100 mg per day) had test meals with and without acarbose 100 mg before and after the treatment period (mean 46 weeks), a test meal with acarbose after 20 weeks of continuous treatment and a final test meal without acarbose 6 weeks after cessation of treatment. Without acarbose mean plasma PYY concentrations rose from a mean basal value of 11.5 +/- 2.9 pmol/l to 19.5 +/- 3.9 pmol/l 120 min postprandially (P less than 0.01). Acarbose treatment did not effect basal plasma PYY concentrations but significantly enhanced food stimulated PYY concentrations acutely, at 20 weeks and at the final treatment test meal. Mean incremental integrated plasma responses (area under curve) rose by 183%, 184% and 169%, respectively (P less than 0.05). After cessation of treatment postprandial responses returned to pretreatment values within 6 weeks. Conversely, the integrated incremetal postprandial plasma responses of glucose and insulin were reversibly reduced by acarbose to 58% +/- 9% and 60% +/- 10% of controls, respectively. Self-assesed side effects of flatulence and more frequent bowel action showed no regular relationship to the PYY response. PYY seems to act as an indicator of the increased carbohydrate load to the distal intestine even in the absence of clinical symptoms. It may contribute to the hypoglycaemic effect of alpha-glucosidase inhibitors by slowing down intestinal transit.

Particle Acceleration and Radiation associated with Magnetic Field Generation from Relativistic Collisionless Shocks

NASA Technical Reports Server (NTRS)

Nishikawa, K.; Hardee, P. E.; Richardson, G. A.; Preece, R. D.; Sol, H.; Fishman, G. J.

2003-01-01

Shock acceleration is an ubiquitous phenomenon in astrophysical plasmas. Plasma waves and their associated instabilities (e.g., the Buneman instability, two-streaming instability, and the Weibel instability) created in the shocks are responsible for particle (electron, positron, and ion) acceleration. Using a 3-D relativistic electromagnetic particle (REMP) code, we have investigated particle acceleration associated with a relativistic jet front propagating through an ambient plasma with and without initial magnetic fields. We find only small differences in the results between no ambient and weak ambient magnetic fields. Simulations show that the Weibel instability created in the collisionless shock front accelerates particles perpendicular and parallel to the jet propagation direction. While some Fermi acceleration may occur at the jet front, the majority of electron acceleration takes place behind the jet front and cannot be characterized as Fermi acceleration. The simulation results show that this instability is responsible for generating and amplifying highly nonuniform, small-scale magnetic fields, which contribute to the electron s transverse deflection behind the jet head. The "jitter" radiation from deflected electrons has different properties than synchrotron radiation which is calculated in a uniform magnetic field. This jitter radiation may be important to understanding the complex time evolution and/or spectral structure in gamma-ray bursts, relativistic jets, and supernova remnants.

Physics of the Geospace Response to Powerful HF Radio Waves

DTIC Science & Technology

2012-10-31

studies of the response of the Earth’s space plasma to high-power HF radio waves from the High-frequency Active Auroral Research Program ( HAARP ...of HF heating and explored to simulate artificial ducts. DMSP- HAARP experiments revealed that HF-created ion outflows and artificial density ducts...in the topside ionosphere appeared faster than predicted by the models, pointing to kinetic (suprathermal) effects. CHAMP/GRACE- HAARP experiments

Effect of 3-D magnetic fields on neutral particle fueling and exhaust in MAST

NASA Astrophysics Data System (ADS)

Flesch, Kurt; Kremeyer, Thierry; Waters, Ian; Schmitz, Oliver; Kirk, Andrew; Harrison, James

2017-10-01

The application of resonant magnetic perturbations (RMPs) is used to suppress edge localized modes but causes in many cases a density pump-out. At MAST, this particle pump out was found to be connected to an amplifying MHD plasma response. An analysis is presented on past MAST discharges to understand the effect of these RMPs on the neutral household and on changes in neutral fueling and exhaust during the pump out. A global, 0-D particle balance model was used to study the neutral dynamics and plasma confinement during shots with and without RMP application. Using the D α emission measured by filterscopes and a calibrated 1-D CCD camera, as well as S/XB coefficients determined by the edge plasma parameters, globally averaged ion confinement times were calculated. In L-mode, discharges with RMPs that caused an MHD response had a 15-20% decrease in confinement time but an increase in total recycling flux. The application of RMPs in H-mode caused either a decrease or no change in confinement, like those in L-mode, depending on the configuration of the RMPs and plasma response. A spectroscopically assisted Penning gauge is being prepared for the next campaign at MAST-U to extend this particle balance to study impurity exhaust with RMPs. This work was funded in part by the U.S. DoE under Grant DE-SC0012315.

Ghrelin-stimulation test in the diagnosis of canine pituitary dwarfism.

PubMed

Bhatti, S F M; De Vliegher, S P; Mol, J A; Van Ham, L M L; Kooistra, H S

2006-08-01

This study investigated whether ghrelin, a potent releaser of growth hormone (GH) secretion, is a valuable tool in the diagnosis of canine pituitary dwarfism. The effect of intravenous administration of ghrelin on the release of GH and other adenohypophyseal hormones was investigated in German shepherd dogs with congenital combined pituitary hormone deficiency and in healthy Beagles. Analysis of the maximal increment (i.e. difference between pre- and maximal post-ghrelin plasma hormone concentration) indicated that the GH response was significantly lower in the dwarf dogs compared with the healthy dogs. In none of the pituitary dwarfs, the ghrelin-induced plasma GH concentration exceeded 5 microg/l at any time. However, this was also true for 3 healthy dogs. In all dogs, ghrelin administration did not affect the plasma concentrations of ACTH, cortisol, TSH, LH and PRL . Thus, while a ghrelin-induced plasma GH concentration above 5 microg/l excludes GH deficiency, false-negative results may occur.

Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer.

PubMed

Robarge, Jason D; Desta, Zereunesay; Nguyen, Anne T; Li, Lang; Hertz, Daniel; Rae, James M; Hayes, Daniel F; Storniolo, Anna M; Stearns, Vered; Flockhart, David A; Skaar, Todd C; Henry, N Lynn

2017-02-01

Inter-individual differences in estrogen concentrations during treatment with aromatase inhibitors (AIs) may contribute to therapeutic response and toxicity. The aim of this study was to determine plasma concentrations of estradiol (E2), estrone (E1), and estrone sulfate (E1S) in a large cohort of AI-treated breast cancer patients. In a randomized, multicenter trial of postmenopausal women with early-stage breast cancer starting treatment with letrozole (n = 241) or exemestane (n = 228), plasma estrogen concentrations at baseline and after 3 months were quantitated using a sensitive mass spectrometry-based assay. Concentrations and suppression below the lower limit of quantification (LLOQ) were compared between estrogens and between drugs. The ranges of baseline estrogen concentrations were

Magnetohydrodynamic simulation study of plasma jets and plasma-surface contact in coaxial plasma accelerators

DOE PAGES

Subramaniam, Vivek; Raja, Laxminarayan L.

2017-06-13

Recent experiments by Loebner et al. [IEEE Trans. Plasma Sci. 44, 1534 (2016)] studied the effect of a hypervelocity jet emanating from a coaxial plasma accelerator incident on target surfaces in an effort to mimic the transient loading created during edge localized mode disruption events in fusion plasmas. In this study, we present a magnetohydrodynamic (MHD) numerical model to simulate plasma jet formation and plasma-surface contact in this coaxial plasma accelerator experiment. The MHD system of equations is spatially discretized using a cell-centered finite volume formulation. The temporal discretization is performed using a fully implicit backward Euler scheme and themore » resultant stiff system of nonlinear equations is solved using the Newton method. The numerical model is employed to obtain some key insights into the physical processes responsible for the generation of extreme stagnation conditions on the target surfaces. Simulations of the plume (without the target plate) are performed to isolate and study phenomena such as the magnetic pinch effect that is responsible for launching pressure pulses into the jet free stream. The simulations also yield insights into the incipient conditions responsible for producing the pinch, such as the formation of conductive channels. The jet-target impact studies indicate the existence of two distinct stages involved in the plasma-surface interaction. A fast transient stage characterized by a thin normal shock transitions into a pseudo-steady stage that exhibits an extended oblique shock structure. A quadratic scaling of the pinch and stagnation conditions with the total current discharged between the electrodes is in qualitative agreement with the results obtained in the experiments. Finally, this also illustrates the dominant contribution of the magnetic pressure term in determining the magnitude of the quantities of interest.« less

Magnetohydrodynamic simulation study of plasma jets and plasma-surface contact in coaxial plasma accelerators

NASA Astrophysics Data System (ADS)

Subramaniam, Vivek; Raja, Laxminarayan L.

2017-06-01

Recent experiments by Loebner et al. [IEEE Trans. Plasma Sci. 44, 1534 (2016)] studied the effect of a hypervelocity jet emanating from a coaxial plasma accelerator incident on target surfaces in an effort to mimic the transient loading created during edge localized mode disruption events in fusion plasmas. In this paper, we present a magnetohydrodynamic (MHD) numerical model to simulate plasma jet formation and plasma-surface contact in this coaxial plasma accelerator experiment. The MHD system of equations is spatially discretized using a cell-centered finite volume formulation. The temporal discretization is performed using a fully implicit backward Euler scheme and the resultant stiff system of nonlinear equations is solved using the Newton method. The numerical model is employed to obtain some key insights into the physical processes responsible for the generation of extreme stagnation conditions on the target surfaces. Simulations of the plume (without the target plate) are performed to isolate and study phenomena such as the magnetic pinch effect that is responsible for launching pressure pulses into the jet free stream. The simulations also yield insights into the incipient conditions responsible for producing the pinch, such as the formation of conductive channels. The jet-target impact studies indicate the existence of two distinct stages involved in the plasma-surface interaction. A fast transient stage characterized by a thin normal shock transitions into a pseudo-steady stage that exhibits an extended oblique shock structure. A quadratic scaling of the pinch and stagnation conditions with the total current discharged between the electrodes is in qualitative agreement with the results obtained in the experiments. This also illustrates the dominant contribution of the magnetic pressure term in determining the magnitude of the quantities of interest.

Magnetohydrodynamic simulation study of plasma jets and plasma-surface contact in coaxial plasma accelerators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Subramaniam, Vivek; Raja, Laxminarayan L.

Recent experiments by Loebner et al. [IEEE Trans. Plasma Sci. 44, 1534 (2016)] studied the effect of a hypervelocity jet emanating from a coaxial plasma accelerator incident on target surfaces in an effort to mimic the transient loading created during edge localized mode disruption events in fusion plasmas. In this study, we present a magnetohydrodynamic (MHD) numerical model to simulate plasma jet formation and plasma-surface contact in this coaxial plasma accelerator experiment. The MHD system of equations is spatially discretized using a cell-centered finite volume formulation. The temporal discretization is performed using a fully implicit backward Euler scheme and themore » resultant stiff system of nonlinear equations is solved using the Newton method. The numerical model is employed to obtain some key insights into the physical processes responsible for the generation of extreme stagnation conditions on the target surfaces. Simulations of the plume (without the target plate) are performed to isolate and study phenomena such as the magnetic pinch effect that is responsible for launching pressure pulses into the jet free stream. The simulations also yield insights into the incipient conditions responsible for producing the pinch, such as the formation of conductive channels. The jet-target impact studies indicate the existence of two distinct stages involved in the plasma-surface interaction. A fast transient stage characterized by a thin normal shock transitions into a pseudo-steady stage that exhibits an extended oblique shock structure. A quadratic scaling of the pinch and stagnation conditions with the total current discharged between the electrodes is in qualitative agreement with the results obtained in the experiments. Finally, this also illustrates the dominant contribution of the magnetic pressure term in determining the magnitude of the quantities of interest.« less

The Properties of 3 Different Plasma Formulations and Their Effects on Tendinopathic Cells.

PubMed

Rubio-Azpeitia, Eva; Bilbao, Ane M; Sánchez, Pello; Delgado, Diego; Andia, Isabel

2016-08-01

Tendinopathies are attributed to failure of the healing process and inadequate tissue remodeling. Plasma injections can trigger regenerative responses by modifying the molecular microenvironment. To examine the differences in the mitotic, chemotactic, anabolic, and inflammatory effects between leukocyte- and platelet-rich plasma (L-PRP), platelet-rich plasma (PRP), and platelet-poor plasma (PPP). Controlled laboratory study. Tendinopathic cells were cultured in 3-dimensional (3D) hydrogels formed using PPP, PRP, and L-PRP. Cell migration was evaluated using a μ-Slide chemotaxis chamber with video microscopy. Proliferation was assessed using XTT assays. Expression of genes associated with matrix turnover, including type 1 collagen (COL1A1), COL3A1, aggrecan, decorin, fibronectin, matrix metalloproteinase 1 (MMP-1), MMP-3, A Disintegrin-Like And Metalloprotease With Thrombospondin Type 1 Motif proteins 4 (ADAMTS-4), and ADAMTS-5, was assessed using real-time reverse-transcription polymerase chain reaction. Secreted inflammatory proteins, including interleukin (IL)-1β, IL-6, IL-8, monocyte chemotactic protein 1 (MCP-1), and regulated on activation, normal T cell expressed and secreted (RANTES), as well as vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF), were quantified using enzyme-linked immunosorbent assay. Tendinopathic cells migrate at a higher velocity along L-PRP and PRP than along PPP gradients. PRP and L-PRP promote hypercellularity. PPP and PRP showed more pronounced anabolic properties, as demonstrated by enhanced COL1A1 and COL3A1 and reduced MMP-1 expression. Decorin, fibronectin, and aggrecan were downregulated in L-PRP compared with PPP and PRP. L-PRP and PRP were shown to be more proinflammatory than PPP in terms of IL-6 secretion, but cells in PPP showed MCP-1(high) phenotype. CTGF secretion was significantly reduced in L-PRP compared with PPP and PRP. The main advantages of L-PRP and PRP use, compared with PPP, include their stronger chemotactic and proliferative properties. While PPP and PRP stimulate matrix anabolism, L-PRP is more proinflammatory. Emphasis should be placed on the temporal needs and biological characteristics of injured tendons, and plasma formulations need to be tailored accordingly. Versatile systems allowing the preparation of different plasma formulations, such as PPP, PRP, or L-PRP, can help refine clinical applications by taking advantage of their different biological properties. © 2016 The Author(s).

Thrombospondin-2 predicts response to treatment with intravenous immunoglobulin in children with Kawasaki disease.

PubMed

Yang, Shuai; Song, Ruixia; Li, Xiaohui; Zhang, Ting; Fu, Jin; Cui, Xiaodai

2018-01-01

To investigate the predictive value of thrombospondin-2 (TSP-2) in assessing the response to intravenous immunoglobulin (IVIG) in children with acute Kawasaki disease (KD). This was a cohort study with controls. 71 children with KD were recruited as the case group, including IVIG non-responder (n=17) and IVIG responder (n=54), and healthy children (n=27) and febrile children (n=30) were used as control groups. ELISA was used to measure plasma TSP-2 and TSP-1 levels. The rank-sum test was used to compare groups of non-normally distributed data. Predictive value was evaluated through the receiver operating characteristic (ROC) curve. Compared with the control groups, the plasma TSP-2 levels in acute KD were significantly elevated (TSP-2: 31.00 (24.02, 39.28) vs 21.93 (17.00, 24.73) vs 16.23 (14.00, 19.64) ng/mL, P<0.001). The plasma TSP-2 level in the IVIG non-responder was significantly higher than the responder group (37.58 (31.86, 43.98) vs 27.84 (21.88, 33.48) ng/mL, P=0.002). When using an ROC curve to analyse the predictive effect of TSP-2 on non-responsiveness to IVIG treatment, the area under the curve was 0.752 (0.630, 0.875) (P=0.002). When the cut-off value for TSP-2 was 31.50 ng/mL, the sensitivity was 82.35%, the specificity was 64.81%. The plasma TSP-2 level was elevated in acute KD and it might be a novel predictor for IVIG resistance, which could help guide clinicians to choose individualised initial therapeutic regimens.

Effects of resistivity and rotation on the linear plasma response to non-axisymmetric magnetic perturbations on DIII-D

DOE PAGES

Haskey, Shaun R.; Lanctot, Matthew J.; Liu, Y. Q.; ...

2015-01-05

Parameter scans show the strong dependence of the plasma response on the poloidal structure of the applied field highlighting the importance of being able to control this parameter using non-axisymmetric coil sets. An extensive examination of the linear single fluid plasma response to n = 3 magnetic perturbations in L-mode DIII-D lower single null plasmas is presented. The effects of plasma resistivity, toroidal rotation and applied field structure are calculated using the linear single fluid MHD code, MARS-F. Measures which separate the response into a pitch-resonant and resonant field amplification (RFA) component are used to demonstrate the extent to whichmore » resonant screening and RFA occurs. The ability to control the ratio of pitch-resonant fields to RFA by varying the phasing between upper and lower resonant magnetic perturbations coils sets is shown. The predicted magnetic probe outputs and displacement at the x-point are also calculated for comparison with experiments. Additionally, modelling of the linear plasma response using experimental toroidal rotation profiles and Spitzer like resistivity profiles are compared with results which provide experimental evidence of a direct link between the decay of the resonant screening response and the formation of a 3D boundary. As a result, good agreement is found during the initial application of the MP, however, later in the shot a sudden drop in the poloidal magnetic probe output occurs which is not captured in the linear single fluid modelling.« less

Quantitative determination of the enantiomers of methadone in human plasma and saliva by chiral column chromatography coupled with mass spectrometric detection.

PubMed

George, Rani; Lobb, Michael; Haywood, Alison; Khan, Sohil; Hardy, Janet; Good, Phillip; Hennig, Stefanie; Norris, Ross

2016-01-01

Methadone is a potent lipophilic synthetic opioid that is effective in the treatment of cancer pain and perceived benefit in difficult pain control scenarios (especially in cases of neuropathic pain). The use of methadone in clinical practice is challenging however, due to the narrow therapeutic window and large inter- and intra-individual variability in therapeutic response. Quantitation of the enantiomers d- and l-methadone (d- and l-MTD) in plasma and saliva provides a basis for studying its pharmacokinetics in patients with cancer and for monitoring efficacy, toxicity and side-effects. This assay involves quantitation of the enantiomers of methadone using their respective deuterated internal standards, in plasma and saliva matrices with no impact of ion suppression in either matrix. The analytical recoveries of d- and l-MTD from the saliva collection devices (Salivette®) are optimised in this novel method with an accurate and simple extraction method employing dichloromethane. Optimal enantioselective separations were achieved using an α1-acid glycoprotein chiral stationary phase and triple quadrupole tandem mass spectrometer. Linearity was demonstrated over 0.05-1000µg/L for both enantiomers in plasma and in saliva with correlation coefficients greater than 0.998. The lower limit of quantitation (LLOQ) was determined to be 0.1µg/L in plasma and saliva for d- and l-MTD. Accuracy of the method ranges from 100% to 106% even at the LLOQ and total precision, expressed as the coefficient of variation, was between 0.2% and 4.4% for both analytes in both matrices. A simple one step extraction procedure resulted in recoveries greater than 95% for both analytes, at concentrations as low as 0.5µg/L, from the Salivette®. The validated method was applied successfully in 14 paired plasma and saliva samples obtained from adult patients with cancer pain receiving methadone. Copyright © 2015 Elsevier B.V. All rights reserved.

Vascular endothelial growth factor during hypoglycemia in patients with type 1 diabetes mellitus: relation to cognitive function and renin-angiotensin system activity.

PubMed

Kristensen, Peter Lommer; Høi-Hansen, Thomas; Boomsma, Frans; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2009-10-01

In healthy adults, levels of vascular endothelial growth factor (VEGF) increase in response to mild hypoglycemia. VEGF is implicated in glucose transport over the blood-brain barrier, and the increase during hypoglycemia has been positively correlated with preservation of cognitive function during hypoglycemia. High activity in the renin-angiotensin system (RAS) is associated with an increased risk of severe hypoglycemia in patients with type 1 diabetes mellitus. Renin-angiotensin system possibly exerts its mechanism in hypoglycemia via VEGF. We studied the impact of mild hypoglycemia on plasma VEGF in patients with type 1 diabetes mellitus and high or low RAS activity and analyzed associations between VEGF levels and cognitive function during hypoglycemia. Eighteen patients with type 1 diabetes mellitus-9 with high and 9 with low RAS activity-underwent a single-blinded, placebo-controlled, crossover study with either mild hypoglycemia or stable glycemia. Cognitive function was assessed by the California Cognitive Assessment Package and the Alzheimer Quick Test. Nadir plasma glucose was 2.2 (0.3) mmol/L. During the control study, plasma VEGF did not change. During hypoglycemia, plasma VEGF increased from 39 to 58 pg/L in the high-RAS group (P = .004) and from 76 to 109 pg/L in the low-RAS group (P = .01), with no difference between RAS groups (P = .9). A weak association between reduced preservation of cognitive function during hypoglycemia and low VEGF response was observed. Plasma VEGF levels increase during mild, short-term hypoglycemia in patients with type 1 diabetes mellitus. The VEGF response is not dependent on RAS activity and only weakly associated with preservation of cognitive function during hypoglycemia. Thus, the previously described association between low RAS activity and better cognitive performance during hypoglycemia does not seem to be mediated by VEGF.

Thin film silicon by a microwave plasma deposition technique: Growth and devices, and, interface effects in amorphous silicon/crystalline silicon solar cells

NASA Astrophysics Data System (ADS)

Jagannathan, Basanth

Thin film silicon (Si) was deposited by a microwave plasma CVD technique, employing double dilution of silane, for the growth of low hydrogen content Si films with a controllable microstructure on amorphous substrates at low temperatures (<400sp°C). The double dilution was achieved by using a Ar (He) carrier for silane and its subsequent dilution by Hsb2. Structural and electrical properties of the films have been investigated over a wide growth space (temperature, power, pressure and dilution). Amorphous Si films deposited by silane diluted in He showed a compact nature and a hydrogen content of ˜8 at.% with a photo/dark conductivity ratio of 10sp4. Thin film transistors (W/L = 500/25) fabricated on these films, showed an on/off ratio of ˜10sp6 and a low threshold voltage of 2.92 volts. Microcrystalline Si films with a high crystalline content (˜80%) were also prepared by this technique. Such films showed a dark conductivity ˜10sp{-6} S/cm, with a conduction activation energy of 0.49 eV. Film growth and properties have been compared for deposition in Ar and He carrier systems and growth models have been proposed. Low temperature junction formation by undoped thin film silicon was examined through a thin film silicon/p-type crystalline silicon heterojunctions. The thin film silicon layers were deposited by rf glow discharge, dc magnetron sputtering and microwave plasma CVD. The hetero-interface was identified by current transport analysis and high frequency capacitance methods as the key parameter controlling the photovoltaic (PV) response. The effect of the interface on the device properties (PV, junction, and carrier transport) was examined with respect to modifications created by chemical treatment, type of plasma species, their energy and film microstructure interacting with the substrate. Thermally stimulated capacitance was used to determine the interfacial trap parameters. Plasma deposition of thin film silicon on chemically clean c-Si created electron trapping sites while hole traps were seen when a thin oxide was present at the interface. Under optimized conditions, a 10.6% efficient cell (11.5% with SiOsb2 A/R) with an open circuit voltage of 0.55 volts and a short circuit current density of 30 mA/cmsp2 was fabricated.

Sodium Aluminate Concentration Effects on Microstructure and Corrosion Behavior of the Plasma Electrolytic Oxidation Coatings on Pure Titanium

NASA Astrophysics Data System (ADS)

Molaei, Maryam; Fattah-Alhosseini, Arash; Gashti, Seyed Omid

2018-01-01

Sodium aluminate (NaAlO2) concentration was varied in order to understand the influence of the chemical composition of electrolyte on the spark characteristics, microstructure, and corrosion behavior of plasma electrolytic oxidation (PEO) coatings. For this purpose, PEO coatings were formed on the pure titanium substrate surface using solutions of four diverse sodium aluminate concentrations (6, 8, 10, and 12 g/L). The PEO process was carried out at constant time and voltage (180 seconds and 420 V). Studying the microstructures of samples by scanning electron microscope (SEM) and their corrosion behavior in 3.5 wt pct NaCl solutions indicated that the increase in NaAlO2 concentration (up to 10 g/L) led to an increase in uniformity and compactness, thus decreasing the size of micro-pores and increment of corrosion resistance. However, at a certain level of NaAlO2 concentration (12 g/L), large and severe sparks were created on the surface of the sample during the process, worsening the corrosion resistance and microstructure of coating.

The effect of the isotope on the H-mode density limit

NASA Astrophysics Data System (ADS)

Huber, A.; Wiesen, S.; Bernert, M.; Brezinsek, S.; Chankin, A. V.; Sergienko, G.; Huber, V.; Abreu, P.; Boboc, A.; Brix, M.; Carralero, D.; Delabie, E.; Eich, T.; Esser, H. G.; Guillemaut, C.; Jachmich, S.; Joffrin, E.; Kallenbach, A.; Kruezi, U.; Lang, P.; Linsmeier, Ch.; Lowry, C. G.; Maggi, C. F.; Matthews, G. F.; Meigs, A. G.; Mertens, Ph.; Reimold, F.; Schweinzer, J.; Sips, G.; Stamp, M.; Viezzer, E.; Wischmeier, M.; Zohm, H.; contributors, JET; ASDEX Upgrade Team

2017-08-01

In order to understand the mechanisms for the H-mode density limit in machines with fully metallic walls, systematic investigations of H-mode density limit plasmas in experiments with deuterium and hydrogen external gas fuelling have been performed on JET-ILW. The observed H-mode density limit on JET in D- as well as in H-plasmas demonstrates similar operation phases: the stable H-mode phase, degrading H-mode, breakdown of the H-mode with energy confinement deterioration accompanied by a dithering cycling phase, followed by the L-mode phase. The density limit is not related to an inward collapse of the hot core plasma due to an overcooling of the plasma periphery by radiation. Indeed, independently of the isotopic effect, the total radiated power stay almost constant during the H-mode phase until the H-L back transition. It was observed in D- and H-plasmas that neither detachment, nor the X-point MARFE itself do trigger the H-L transition and that they thus do not present a limit on the plasma density. It is the plasma confinement, most likely determined by edge parameters, which is ultimately responsible for the H-mode DL. By comparing similar discharges but fuelled with either deuterium or hydrogen, we have found that the H-mode density limit exhibits a dependence on the isotope mass: the density limit is up to 35% lower in hydrogen compared to similar deuterium plasma conditions (the obtained density limit is in agreement with the Greenwald limit for D-plasma). In addition, the density limit is nearly independent of the applied power both in deuterium or hydrogen fuelling conditions. The measured Greenwald fractions are consistent with the predictions from a theoretical model based on an MHD instability theory in the near-SOL. The JET operational domains are significantly broadened when increasing the plasma effective mass (e.g. tritium or deuterium-tritium operation), i.e. the L to H power threshold is reduced whereas the density limit for the L-mode back transition is increased.

Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: a randomized, double blind placebo controlled trial.

PubMed

Bundy, Rafe; Walker, Ann F; Middleton, Richard W; Wallis, Carol; Simpson, Hugh C R

2008-09-01

Cardiovascular diseases are the chief causes of death in the UK, and are associated with high circulating levels of total cholesterol in the plasma. Artichoke leaf extracts (ALEs) have been reported to reduce plasma lipids levels, including total cholesterol, although high quality data is lacking. The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia. 131 adults were screened for total plasma cholesterol in the range 6.0-8.0 mmol/l, with 75 suitable volunteers randomised onto the trial. Volunteers consumed 1280 mg of a standardised ALE, or matched placebo, daily for 12 weeks. Plasma total cholesterol decreased in the treatment group by an average of 4.2% (from 7.16 (SD 0.62) mmol/l to 6.86 (SD 0.68) mmol/l) and increased in the control group by an average of 1.9% (6.90 (SD 0.49) mmol/l to 7.03 (0.61) mmol/l), the difference between groups being statistically significant (p=0.025). No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or triglyceride levels. General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favourable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response.

Investigation of Hair Follicle and Plasma Biomarkers for Low-Level VX Vapor Exposure

DTIC Science & Technology

2006-11-01

hydroxyxanthotoxin L-Methionine response 5 Poly- L – Glutamate L-Valine Pyridoxal 2-Naphthylamine Uridine 4- oxoproline L-Citrulline e 5 ...verified in the bulb region of the follicle except Na+/K+-ATPase α1. Figure 1. 5 Figure 1: Western Blot of total rat follicle bulb...protein separated by 10-20% SDS-PAGE. The lanes are: 1: BioRad Kaleidoscope Molecular Weight Ladder; 2: BRCA 1; 3: GAPDH; 4: Keratin 10; 5

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS): a 24-year clinical experience with 178 patients

PubMed Central

Levandovsky, Mark; Harvey, Danielle; Lara, Primo; Wun, Ted

2008-01-01

Background Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome (TTP-HUS) are related and uncommon disorders with a high fatality and complication rate if untreated. Plasma exchange therapy has been shown to produce high response rates and improve survival in patients with many forms of TTP-HUS. We performed a retrospective cohort study of 178 consecutively treated patients with TTP-HUS and analyzed whether clinical or laboratory characteristics could predict for important short- and long-term outcome measures. Results Overall 30-day mortality was 16% (n = 27). 171 patients (96%) received plasma exchange as the principal treatment, with a mean of 8 exchanges and a mean cumulative infused volume of 42 ± 71 L of fresh frozen plasma. The rate of complete response was 65% or 55% depending on whether this was defined by a platelet count of 100,000/μl or 150,000/μl, respectively. The rate of relapse was 18%. The Clinical Severity Score did not predict for 30-day mortality or relapse. The time to complete response did not predict for relapse. Renal insufficiency at presentation was associated with a decreased risk of relapse, with each unit increase in serum creatinine associated with a 40% decreased odds of relapse. 72% of our cohort had an idiopathic TTP-sporadic HUS, while 17% had an underlying cancer, received a solid organ transplant or were treated with a mitomycin-based therapy. The estimated overall 5-year survival was 55% and was significantly better in those without serious underlying conditions. Conclusion Plasma exchange therapy produced both high response and survival rates in this large cohort of patients with TTP-HUS. The Clinical Severity Score did not predict for 30-day mortality or relapse, contrary to our previous findings. Interestingly, the presence of renal insufficiency was associated with a decreased risk of relapse. The most important predictor of mortality was the presence or absence of a serious underlying disorder. PMID:19046460

Human Platelet-Rich Plasma- and Extracellular Matrix-Derived Peptides Promote Impaired Cutaneous Wound Healing In Vivo

PubMed Central

Demidova-Rice, Tatiana N.; Wolf, Lindsey; Deckenback, Jeffry; Hamblin, Michael R.; Herman, Ira M.

2012-01-01

Previous work in our laboratory has described several pro-angiogenic short peptides derived from endothelial extracellular matrices degraded by bacterial collagenase. Here we tested whether these peptides could stimulate wound healing in vivo. Our experiments demonstrated that a peptide created as combination of fragments of tenascin X and fibrillin 1 (comb1) applied into cranial dermal wounds created in mice treated with cyclophosphamide to impair wound healing, can improve the rate of wound closure. Furthermore, we identify and characterize a novel peptide (UN3) created and modified from two naturally-occurring peptides, which are present in human platelet-rich plasma. In vitro testing of UN3 demonstrates that it causes a 50% increase in endothelial proliferation, 250% increase in angiogenic response and a tripling of epithelial cell migration in response to injury. Results of in vivo experiments where comb1 and UN3 peptides were added together to cranial wounds in cyclophosphamide-treated mice leads to improvement of wound vascularization as shown by an increase of the number of blood vessels present in the wound beds. Application of the peptides markedly promotes cellular responses to injury and essentially restores wound healing dynamics to those of normal, acute wounds in the absence of cyclophosphamide impairment. Our current work is aimed at understanding the mechanisms underlying the stimulatory effects of these peptides as well as identification of the cellular receptors mediating these effects. PMID:22384158

Dynamic Processes at the Outer Boundary of the Magnetosphere, Including Coupling to the Ionosphere

DTIC Science & Technology

1994-04-15

numerical simulation, of the stability of laminar flow in the equatorial LLBL in the presence of coupling to the ionosphere and associated nonuniform ...L.C. Laec Theory of inaperfcs eto lhreio s1w dependenceors dependenceon theelecio precpittion associated coupling. GeV*li. Res. Lair ... nonuniform magnetic field, the nonuniformity being created by electic currents that connect the plasma in the layer to two conducting plates which

Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial.

PubMed

Cheng, Chung Yuen; Chung, Wai Yuen; Szeto, Yim Tong; Benzie, Iris F F

2005-01-01

Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.

NaCl regulation of plasma membrane H(+)-ATPase gene expression in a glycophyte and a halophyte.

PubMed

Niu, X; Narasimhan, M L; Salzman, R A; Bressan, R A; Hasegawa, P M

1993-11-01

NaCl regulation of plasma membrane H(+)-ATPase gene expression in the glycophyte tobacco (Nicotiana tabacum L. var Wisconsin 38) and the halophyte Atriplex nummularia L. was evaluated by comparison of organ-specific mRNA abundance using homologous cDNA probes encoding the ATPases of the respective plants. Accumulation of mRNA was induced by NaCl in fully expanded leaves and in roots but not in expanding leaves or stems. The NaCl responsiveness of the halophyte to accumulate plasma membrane H(+)-ATPase mRNA in roots was substantially greater than that of the glycophyte. Salt-induced transcript accumulation in A. nummularia roots was localized by in situ hybridization predominantly to the elongation zone, but mRNA levels also increased in the zone of differentiation. Increased message accumulation in A. nummularia roots could be detected within 8 h after NaCl (400 mM) treatment, and maximal levels were severalfold greater than in roots of untreated control plants. NaCl-induced plasma membrane H(+)-ATPase gene expression in expanded leaves and roots presumably indicates that these organs require increased H(+)-electrochemical potential gradients for the maintenance of plant ion homeostasis for salt adaptation. The greater capacity of the halophyte to induce plasma membrane H(+)-ATPase gene expression in response to NaCl may be a salt-tolerance determinant.

NaCl regulation of plasma membrane H(+)-ATPase gene expression in a glycophyte and a halophyte.

PubMed Central

Niu, X; Narasimhan, M L; Salzman, R A; Bressan, R A; Hasegawa, P M

1993-01-01

NaCl regulation of plasma membrane H(+)-ATPase gene expression in the glycophyte tobacco (Nicotiana tabacum L. var Wisconsin 38) and the halophyte Atriplex nummularia L. was evaluated by comparison of organ-specific mRNA abundance using homologous cDNA probes encoding the ATPases of the respective plants. Accumulation of mRNA was induced by NaCl in fully expanded leaves and in roots but not in expanding leaves or stems. The NaCl responsiveness of the halophyte to accumulate plasma membrane H(+)-ATPase mRNA in roots was substantially greater than that of the glycophyte. Salt-induced transcript accumulation in A. nummularia roots was localized by in situ hybridization predominantly to the elongation zone, but mRNA levels also increased in the zone of differentiation. Increased message accumulation in A. nummularia roots could be detected within 8 h after NaCl (400 mM) treatment, and maximal levels were severalfold greater than in roots of untreated control plants. NaCl-induced plasma membrane H(+)-ATPase gene expression in expanded leaves and roots presumably indicates that these organs require increased H(+)-electrochemical potential gradients for the maintenance of plant ion homeostasis for salt adaptation. The greater capacity of the halophyte to induce plasma membrane H(+)-ATPase gene expression in response to NaCl may be a salt-tolerance determinant. PMID:8022933

Complement Activation on Platelets Correlates with a Decrease in Circulating Immature Platelets in Patients with Immune Thrombocytopenic Purpura

PubMed Central

Peerschke, Ellinor I.B.; Andemariam, Biree; Yin, Wei; Bussel, James B.

2010-01-01

The role of the complement system in immune thrombocytopenic purpura (ITP) is not well defined. We examined plasma from 79 patients with ITP, 50 healthy volunteers, and 25 patients with non-immune mediated thrombocytopenia, to investigate their complement activation/fixation capacity (CAC) on immobilized heterologous platelets. Enhanced CAC was found in 46 plasma samples (59%) from patients with ITP, but no samples from patients with non-immune mediated thrombocytopenia. Plasma from healthy volunteers was used for comparison. In patients with ITP, an enhanced plasma CAC was associated with a decreased circulating absolute immature platelet fraction (A-IPF) (<15 × 109/L) (p = 0.027) and thrombocytopenia (platelet count less than 100K/μl) (p= 0.024). The positive predictive value of an enhanced CAC for a low A-IPF was 93%, with a specificity of 77%. The specificity and positive predictive values increased to 100% when plasma CAC was defined strictly by enhanced C1q and/or C4d deposition on test platelets. Although no statistically significant correlation emerged between CAC and response to different pharmacologic therapies, an enhanced response to splenectomy was noted (p <0.063). Thus, complement fixation may contribute to the thrombocytopenia of ITP by enhancing clearance of opsonized platelets from the circulation, and/or directly damaging platelets and megakaryocytes. PMID:19925495

Plasma volume and water/sodium balance differences due to sex and menstrual phase after 4 hours of head-down bed rest (HDBR).

NASA Astrophysics Data System (ADS)

Edgell, Heather; Grinberg, Anna; Beavers, Keith; Gagne, Nathalie; Totosy de Zepetnek, Julia; Greaves, Danielle; Hughson, Richard L.

In both sexes, orthostatic responses are impaired by spaceflight or head-down bed-rest (HDBR), with a greater impact in women. Decreased plasma volume (PV) could contribute to reductions in cardiac output and blood pressure upon an orthostatic challenge. We hypothesized that a greater decrease in PV in women might lead to poorer orthostatic responses. We further hypothesized that the responses in women would differ throughout the menstrual cycle. We studied the responses of men (n=6) and women (n= 6) to 4-hr HDBR and 4-hr seated control (SEAT). Furthermore, we studied women in both the follicular (Day 8-11) and luteal (Day 18-24) phases of menstruation in a repeated measures design. After 4-hr HDBR, PV decreased in men (-175.1 ± 56.8 mL; vs. SEAT: P=0.076) and in the follicular phase, but did not change in the luteal phase (Luteal: -55.0 ± 54.6 mL; Follicular: -226.4 ± 88.2 mL (Interaction effect: P=0.01)). After 4-hr HDBR, only men appear to exhibit increased urine volume (Men, difference from SEAT: +298.3 ± 105.5 mL; Luteal, difference from SEAT: +59.4 ± 34.3 mL; Follicular, difference from SEAT: +43.7 ± 190.0 mL; P=0.16). No changes in urinary sodium after 4-hr HDBR were observed in any group (Men, difference from SEAT: -16.5 ± 13.5 µmol; Luteal, difference from SEAT: -8.0 ± 8.8 µmol; Follicular, difference from SEAT: +28.2 ± 29.5 µmol; P=0.264). No changes in urinary osmolarity were observed after 4-hr HDBR in any group (Men, difference from SEAT: -38.8 ± 126.2 mmol/kg; Luteal, difference from SEAT: -85.1 ± 66.9 mmol/kg; Follicular, difference from SEAT: -99.1 ± 98.5 mmol/kg; P=0.906). The changes in plasma volume do not appear to be a result of urinary water and sodium loss. Perhaps actions of atrial natriuretic peptide, urodilatin, the RAAS pathway, and/or capillary filtration are involved. From these observed changes in plasma volume, we surmise that women in the follicular phase of the menstrual cycle may exhibit lower cardiac output and thus blood pressure upon an orthostatic challenge in comparison to women in the luteal phase. Future analysis of this project will determine this. Funding provided by the CSA (Space Science Enhancement Program).

A mixed diet supplemented with L-arabinose does not alter glycaemic or insulinaemic responses in healthy human subjects.

PubMed

Halschou-Jensen, Kia; Bach Knudsen, Knud E; Nielsen, Søren; Bukhave, Klaus; Andersen, Jens R

2015-01-14

In addition to a yet-to-be published study showing arabinose to have an inhibiting effect on maltase, in vitro studies have shown L-arabinose to exert an inhibiting effect on small-intestinal sucrase and maltase and the consumption of a sucrose-rich drink containing L-arabinose to exert positive effects on postprandial blood glucose, insulin and C-peptide responses in humans. However, the effects of adding L-arabinose to mixed meals on the indices of glucose control are unknown. The purpose of the present study was to investigate whether the positive effects of L-arabinose added to a sugar drink could be reproduced in subjects consuming a mixed meal containing sucrose and/or starch from wheat flour. A total of seventeen healthy men participated in study 1, a randomised, double-blind, cross-over trial. In this study, the subjects consumed two different breakfast meals containing sucrose and starch from wheat flour (meal A) or starch from wheat flour (meal B) supplemented with 0, 5 and 10 % L-arabinose by weight after a 12 h fast. A total of six healthy men participated in study 2, a randomised, double-blind, cross-over trial. In this study, the subjects also consumed meal B served in two different textures and a liquid meal with maltose supplemented with 0 and 20% L-arabinose. In addition, 1·5 g of paracetamol was chosen as an indirect marker to assess gastric emptying. Postprandial plasma glucose, insulin and C-peptide concentrations were measured regularly for 3 h. The results of the present study showed that the peak plasma concentration, time to reach peak plasma concentration or AUC values of glucose, insulin and C-peptide were not altered after consumption of the test meals. Overall, it was not possible to reproduce the beneficial effects of L-arabinose added to sucrose drinks when L-arabinose was mixed in a solid or semi-solid mixed meal.

Application of Plackett-Burman and Doehlert designs for optimization of selenium analysis in plasma with electrothermal atomic absorption spectrometry.

PubMed

El Ati-Hellal, Myriam; Hellal, Fayçal; Hedhili, Abderrazek

2014-10-01

The aim of this study was the optimization of selenium determination in plasma samples with electrothermal atomic absorption spectrometry using experimental design methodology. 11 variables being able to influence selenium analysis in human blood plasma by electrothermal atomic absorption spectrometry (ETAAS) were evaluated with Plackett-Burman experimental design. These factors were selected from sample preparation, furnace program and chemical modification steps. Both absorbance and background signals were chosen as responses in the screening approach. Doehlert design was used for method optimization. Results showed that only ashing temperature has a statistically significant effect on the selected responses. Optimization with Doehlert design allowed the development of a reliable method for selenium analysis with ETAAS. Samples were diluted 1/10 with 0.05% (v/v) TritonX-100+2.5% (v/v) HNO3 solution. Optimized ashing and atomization temperatures for nickel modifier were 1070°C and 2270°C, respectively. A detection limit of 2.1μgL(-1) Se was obtained. Accuracy of the method was checked by the analysis of selenium in Seronorm™ Trace element quality control serum level 1. The developed procedure was applied for the analysis of total selenium in fifteen plasma samples with standard addition method. Concentrations ranged between 24.4 and 64.6μgL(-1), with a mean of 42.6±4.9μgL(-1). The use of experimental designs allowed the development of a cheap and accurate method for selenium analysis in plasma that could be applied routinely in clinical laboratories. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats.

PubMed

Ait-Belgnaoui, Afifa; Durand, Henri; Cartier, Christel; Chaumaz, Gilles; Eutamene, Hélène; Ferrier, Laurent; Houdeau, Eric; Fioramonti, Jean; Bueno, Lionel; Theodorou, Vassilia

2012-11-01

Intestinal barrier impairment is incriminated in the pathophysiology of intestinal gut disorders associated with psychiatric comorbidity. Increased intestinal permeability associated with upload of lipopolysaccharides (LPS) translocation induces depressive symptoms. Gut microbiota and probiotics alter behavior and brain neurochemistry. Since Lactobacillus farciminis suppresses stress-induced hyperpermeability, we examined whether (i) L. farciminis affects the HPA axis stress response, (ii) stress induces changes in LPS translocation and central cytokine expression which may be reversed by L. farciminis, (iii) the prevention of "leaky" gut and LPS upload are involved in these effects. At the end of the following treatments female rats were submitted to a partial restraint stress (PRS) or sham-PRS: (i) oral administration of L. farciminis during 2 weeks, (ii) intraperitoneal administration of ML-7 (a specific myosin light chain kinase inhibitor), (iii) antibiotic administration in drinking water during 12 days. After PRS or sham-PRS session, we evaluated LPS levels in portal blood, plasma corticosterone and adrenocorticotropic hormone (ACTH) levels, hypothalamic corticotropin releasing factor (CRF) and pro-inflammatory cytokine mRNA expression, and colonic paracellular permeability (CPP). PRS increased plasma ACTH and corticosterone; hypothalamic CRF and pro-inflammatory cytokine expression; CPP and portal blood concentration of LPS. L. farciminis and ML-7 suppressed stress-induced hyperpermeability, endotoxemia and prevented HPA axis stress response and neuroinflammation. Antibiotic reduction of luminal LPS concentration prevented HPA axis stress response and increased hypothalamic expression of pro-inflammatory cytokines. The attenuation of the HPA axis response to stress by L. farciminis depends upon the prevention of intestinal barrier impairment and decrease of circulating LPS levels. Copyright © 2012 Elsevier Ltd. All rights reserved.

Vitamin D Status in Patients With Stage IV Colorectal Cancer: Findings From Intergroup Trial N9741

PubMed Central

Ng, Kimmie; Sargent, Daniel J.; Goldberg, Richard M.; Meyerhardt, Jeffrey A.; Green, Erin M.; Pitot, Henry C.; Hollis, Bruce W.; Pollak, Michael N.; Fuchs, Charles S.

2011-01-01

Purpose Previous studies have suggested that higher plasma 25-hydroxyvitamin D3 [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival, but the prevalence of vitamin D deficiency in advanced colorectal cancer and its influence on outcomes are unknown. Patients and Methods We prospectively measured plasma 25(OH)D levels in 515 patients with stage IV colorectal cancer participating in a randomized trial of chemotherapy. Vitamin D deficiency was defined as 25(OH)D lower than 20 ng/mL, insufficiency as 20 to 29 ng/mL, and sufficiency as ≥ 30 ng/mL. We examined the association between baseline 25(OH)D level and selected patient characteristics. Cox proportional hazards models were used to calculate hazard ratios (HR) for death, disease progression, and tumor response, adjusted for prognostic factors. Results Among 515 eligible patients, 50% of the study population was vitamin D deficient, and 82% were vitamin D insufficient. Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other race (median, 10.7 v 21.1 v 19.3 ng/mL, respectively; P < .001), and females compared to males (median, 18.3 v 21.7 ng/mL, respectively; P = .0005). Baseline plasma 25(OH)D levels were not associated with patient outcome, although given the distribution of plasma levels in this cohort, statistical power for survival analyses were limited. Conclusion Vitamin D deficiency is highly prevalent among patients with stage IV colorectal cancer receiving first-line chemotherapy, particularly in black and female patients. PMID:21422438

Vitamin D status in patients with stage IV colorectal cancer: findings from Intergroup trial N9741.

PubMed

Ng, Kimmie; Sargent, Daniel J; Goldberg, Richard M; Meyerhardt, Jeffrey A; Green, Erin M; Pitot, Henry C; Hollis, Bruce W; Pollak, Michael N; Fuchs, Charles S

2011-04-20

Previous studies have suggested that higher plasma 25-hydroxyvitamin D(3) [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival, but the prevalence of vitamin D deficiency in advanced colorectal cancer and its influence on outcomes are unknown. We prospectively measured plasma 25(OH)D levels in 515 patients with stage IV colorectal cancer participating in a randomized trial of chemotherapy. Vitamin D deficiency was defined as 25(OH)D lower than 20 ng/mL, insufficiency as 20 to 29 ng/mL, and sufficiency as ≥ 30 ng/mL. We examined the association between baseline 25(OH)D level and selected patient characteristics. Cox proportional hazards models were used to calculate hazard ratios (HR) for death, disease progression, and tumor response, adjusted for prognostic factors. Among 515 eligible patients, 50% of the study population was vitamin D deficient, and 82% were vitamin D insufficient. Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other race (median, 10.7 v 21.1 v 19.3 ng/mL, respectively; P < .001), and females compared to males (median, 18.3 v 21.7 ng/mL, respectively; P = .0005). Baseline plasma 25(OH)D levels were not associated with patient outcome, although given the distribution of plasma levels in this cohort, statistical power for survival analyses were limited. Vitamin D deficiency is highly prevalent among patients with stage IV colorectal cancer receiving first-line chemotherapy, particularly in black and female patients.

Biochemical, physiological, and performance response of a functional watermelon juice enriched in L-citrulline during a half-marathon race

PubMed Central

Martínez-Sánchez, Ascensión; Ramos-Campo, Domingo J.; Fernández-Lobato, Bárbara; Rubio-Arias, Jacobo A.; Alacid, Fernando; Aguayo, Encarna

2017-01-01

ABSTRACT Background: Watermelon is a rich natural source of l-citrulline. This non-essential amino acid increases exercise performance. Objective: Evaluate the effect of Fashion watermelon juice enriched in l-citrulline (CWJ) (3.45 g per 500 mL) in physical performance and biochemical markers after a half-marathon race. Design: A randomised, double blind, crossover design where 2 h after drinking 500 mL of CWJ or placebo (PLA, beverage without l-citrulline) amateur male runners performed two half-marathon races. Jump height, heart rate and rating of perceived exertion were evaluated before and after the races. Moreover, muscle soreness and plasma markers of muscle damage and metabolism were evaluated for 72 h after the races. Results: Muscle soreness perception was significantly lower from 24 to 72 h after the race with CWJ beverage. Immediately after the races, runners under CWJ condition showed plasma lactate and glucose concentrations significantly lower and higher lactate dehydrogenase and l-arginine concentration than runners under PLA. A maintenance of jump heights after the races under CWJ supplementation was found, decreasing significantly with PLA. Conclusion: A single Fashion watermelon juice enriched in l-citrulline dose diminished muscle soreness perception from 24 to 72 h after the race and maintained lower concentrations of plasma lactate after an exhausting exercise. PMID:28659740

Influence of electron injection into 27 cm audio plasma cell on the plasma diagnostics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haleem, N. A.; Ragheb, M. S.; Zakhary, S. G.

2013-08-15

In this article, the plasma is created in a Pyrex tube (L = 27 cm, φ= 4 cm) as a single cell, by a capacitive audio frequency (AF) discharge (f = 10–100 kHz), at a definite pressure of ∼0.2 Torr. A couple of tube linear and deviating arrangements show plasma characteristic conformity. The applied AF plasma and the injection of electrons into two gas mediums Ar and N{sub 2} revealed the increase of electron density at distinct tube regions by one order to attain 10{sup 13}/cm{sup 3}. The electrons temperature and density strengths are in contrast to each other. Whilemore » their distributions differ along the plasma tube length, they show a decaying sinusoidal shape where their peaks position varies by the gas type. The electrons injection moderates electron temperature and expands their density. The later highest peak holds for the N{sub 2} gas, at electrons injection it changes to hold for the Ar. The sinusoidal decaying density behavior generates electric fields depending on the gas used and independent of tube geometry. The effect of the injected electrons performs a responsive impact on electrons density not attributed to the gas discharge. Analytical tools investigate the interaction of the plasma, the discharge current, and the gas used on the electrodes. It points to the emigration of atoms from each one but for greater majority they behave to a preferred direction. Meanwhile, only in the linear regime, small percentage of atoms still moves in reverse direction. Traces of gas atoms revealed on both electrodes due to sheath regions denote lack of their participation in the discharge current. In addition, atoms travel from one electrode to the other by overcoming the sheaths regions occurring transportation of particles agglomeration from one electrode to the other. The electrons injection has contributed to increase the plasma electron density peaks. These electrons populations have raised the generated electrostatic fields assisting the elemental ions emigration to a preferred electrode direction. Regardless of plasma electrodes positions and plasma shape, ions can be departed from one electrode to deposit on the other one. In consequence, as an application the AF plasma type can enhance the metal deposition from one electrode to the other.« less

Suppression of plasma virus load below the detection limit of a human immunodeficiency virus kit is associated with longer virologic response than suppression below the limit of quantitation.

PubMed

Raboud, J M; Rae, S; Hogg, R S; Yip, B; Sherlock, C H; Harrigan, P R; O'Shaughnessy, M V; Montaner, J S

1999-10-01

Suppression of human immunodeficiency virus type 1 plasma virus load (PVL) to <20 copies/mL is associated with a longer virologic response after initiation of antiretroviral therapy. The relationship between duration of virologic response and PVL nadir according to a less sensitive assay was explored. When compared with subjects with a PVL nadir >500 copies/mL, the relative risks of PVL rising above 1000 copies/mL for participants in the INCAS trial and the British Columbia Drug Treatment Program with a PVL nadir below the limit of detection (LOD) were 0.04 (95% confidence interval [CI], 0.02-0.09) and 0.06 (95% CI, 0.03-0.12), respectively. The corresponding relative risks for persons with a detectable but not quantifiable PVL nadir were 0.25 (95% CI, 0.13-0.50) and 0.54 (95% CI, 0.25-1.19). The relative risks of virologic failure associated with a PVL nadir detectable but not quantifiable and a PVL nadir below the LOD were statistically different (P<.0001) in both data sets.

The effect of mass loading on the temperature of a flowing plasma. [in vicinity of Io

NASA Technical Reports Server (NTRS)

Linker, Jon A.; Kivelson, Margaret G.; Walker, Raymond J.

1989-01-01

How the addition of ions at rest (mass loading) affects the temperature of a flowing plasma in a MHD approximation is investigated, using analytic theory and time dependent, three-dimensional MHD simulations of plasma flow past Io. The MHD equations show that the temperature can increase or decrease relative to the background, depending on the local sonic Mach number M(S), of the flow. For flows with M(S) of greater than sq rt 9/5 (when gamma = 5/3), mass loading increases the plasma temperature. However, the simulations show a nonlinear response to the addition of mass. If the mass loading rate is large enough, the temperature increase may be smaller than expected, or the temperature may actually decrease, because a large mass loading rate slows the flow and decreases the thermal energy of the newly created plasma.

Cellular transport of l-arginine determines renal medullary blood flow in control rats, but not in diabetic rats despite enhanced cellular uptake capacity.

PubMed

Persson, Patrik; Fasching, Angelica; Teerlink, Tom; Hansell, Peter; Palm, Fredrik

2017-02-01

Diabetes mellitus is associated with decreased nitric oxide bioavailability thereby affecting renal blood flow regulation. Previous reports have demonstrated that cellular uptake of l-arginine is rate limiting for nitric oxide production and that plasma l-arginine concentration is decreased in diabetes. We therefore investigated whether regional renal blood flow regulation is affected by cellular l-arginine uptake in streptozotocin-induced diabetic rats. Rats were anesthetized with thiobutabarbital, and the left kidney was exposed. Total, cortical, and medullary renal blood flow was investigated before and after renal artery infusion of increasing doses of either l-homoarginine to inhibit cellular uptake of l-arginine or N ω -nitro- l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase. l-Homoarginine infusion did not affect total or cortical blood flow in any of the groups, but caused a dose-dependent reduction in medullary blood flow. l-NAME decreased total, cortical and medullary blood flow in both groups. However, the reductions in medullary blood flow in response to both l-homoarginine and l-NAME were more pronounced in the control groups compared with the diabetic groups. Isolated cortical tubular cells displayed similar l-arginine uptake capacity whereas medullary tubular cells isolated from diabetic rats had increased l-arginine uptake capacity. Diabetics had reduced l-arginine concentrations in plasma and medullary tissue but increased l-arginine concentration in cortical tissue. In conclusion, the reduced l-arginine availability in plasma and medullary tissue in diabetes results in reduced nitric oxide-mediated regulation of renal medullary hemodynamics. Cortical blood flow regulation displays less dependency on extracellular l-arginine and the upregulated cortical tissue l-arginine may protect cortical hemodynamics in diabetes. Copyright © 2017 the American Physiological Society.

Prediction of winter vitamin D status and requirements in the UK population based on 25(OH) vitamin D half-life and dietary intake data.

PubMed

Schoenmakers, Inez; Gousias, Petros; Jones, Kerry S; Prentice, Ann

2016-11-01

On a population basis, there is a gradual decline in vitamin D status (plasma 25(OH)D) throughout winter. We developed a mathematical model to predict the population winter plasma 25(OH)D concentration longitudinally, using age-specific values for 25(OH)D expenditure (25(OH)D 3 t 1/2 ), cross-sectional plasma 25(OH)D concentration and vitamin D intake (VDI) data from older (70+ years; n=492) and younger adults (18-69 years; n=448) participating in the UK National Diet and Nutrition Survey. From this model, the population VDI required to maintain the mean plasma 25(OH)D at a set concentration can be derived. As expected, both predicted and measured population 25(OH)D (mean (95%CI)) progressively declined from September to March (from 51 (40-61) to 38 (36-41)nmol/L (predicted) vs 38 (27-48)nmol/L (measured) in older people and from 59 (54-65) to 34 (31-37)nmol/L (predicted) vs 37 (31-44)nmol/L (measured) in younger people). The predicted and measured mean values closely matched. The predicted VDIs required to maintain mean winter plasma 25(OH)D at 50nmol/L at the population level were 10 (0-20) to 11 (9-14) and 11 (6-16) to 13(11-16)μg/d for older and younger adults, respectively dependent on the month. In conclusion, a prediction model accounting for 25(OH)D 3 t 1/2 , VDI and scaling factor for the 25(OH)D response to VDI, closely predicts measured population winter values. Refinements of this model may include specific scaling factors accounting for the 25(OH)D response at different VDIs and as influenced by body composition and specific values for 25(OH)D 3 t 1/2 dependent on host factors such as kidney function. This model may help to reduce the need for longitudinal measurements. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Method and apparatus for upshifting light frequency by rapid plasma creation

DOEpatents

Dawson, John M.; Wilks, Scott C.; Mori, Warren B.; Joshi, Chandrasekhar J.; Sessler, Andrew M.

1990-01-01

Photons of an electromagnetic source wave are frequency-upshifted as a plasma is rapidly created around the path of this propagating source wave. The final frequency can be controlled by adjusting the gas density. A controlled time-varying frequency (chirped) pulse can be produced by using a controlled spatially varying gas density. The plasma must be created in a time which is short compared to the transit time of the light through the plasmas region. For very fast creation over one to at most a few light periods of an overdense plasma, static magnetic fields with short wavelengths are created.

Pharmacology of the meglitinide analogs: new treatment options for type 2 diabetes mellitus.

PubMed

Malaisse, Willy J

2003-01-01

The expression meglitinide analogs was introduced in 1995 to cover new molecules proposed as non-sulfonylurea insulinotropic agents and displaying structural analogy with meglitinide, such as repaglinide, nateglinide, and mitiglinide. Meglitinide analogs display, as judged by conformation analysis, a U-shaped configuration similar to that of antihyperglycemic sulfonylureas such as glibenclamide (glyburide) and glimepiride. In rat pancreatic islets incubated in the presence of 7.0 mmol/L D-glucose, repaglinide and mitiglinide demonstrate comparable concentration-response relationships for stimulation of insulin release, with a threshold value < 10 nmol/L and a maximal secretory response at about 10 nmol/L. Several findings indicate that meglitinide analogs provoke the closing of adenosine triphosphate-sensitive potassium channels, with subsequent gating of voltage-sensitive calcium channels. The effects of meglitinide analogs upon the binding of [3H]glibenclamide to islet cells membranes reinforces this concept. At variance, however, with other meglitinide analogs, the ionic and secretory response to repaglinide (10 micromol/L) is not rapidly reversible in perifused rat islets. In experiments conducted in vivo in control and diabetic rats, repaglinide provokes a greater and more rapid increase in plasma insulin concentration and an earlier fall in glycemia than glibenclamide or glimepiride. Onset of effect is also more rapid and duration of effect shorter with nateglinide versus glibenclamide. In clinical studies, single or repeated daily administration of repaglinide increased plasma insulin concentration in a dose-dependent manner, with an incremental peak reached about 2 hours after repaglinide intake. Plasma concentrations of repaglinide are about 5.0 microg/L 2-2.5 hours after oral intake of the drug. Despite the slow reversibility of repaglinide action in vitro, this drug offers advantages over glibenclamide in terms of the possible occurrence of hypoglycemia if a meal is missed. In volunteers receiving a single oral dose of nateglinide (120mg) 10 minutes before a standardized 800 Kcal breakfast, the plasma insulin concentration was higher 5, 10, and 20 minutes after meal intake than when they received a single dose of repaglinide (0.5 or 2.0mg) or placebo 10 minutes before breakfast. Peak plasma concentrations of nateglinide were reached within 2 hours in most volunteers. Peak plasma concentrations of mitiglinide were reached 30 minutes after a single oral dose in a representative volunteer. Mitiglinide significantly suppressed meal-induced elevations in blood glucose concentrations in a study of patients with type 2 diabetes. In conclusion, two obvious differences among these meglitinide analogs should be underlined. First, on a molar basis, nateglinide is somewhat less potent than repaglinide or mitiglinide, as an insulinotropic agent. The maximal secretory responses evoked by these three meglitinide analogs are, however, identical to one another. Secondly, and as already mentioned, the functional effects of nateglinide and mitiglinide are more rapidly reversible than those of repaglinide, for instance in perifused rat islets. The meglitinide analogs offer the advantage over the long-acting antihyperglycemic sulfonylurea glibenclamide of minimizing the risk of undesirable hypoglycemia.

Plasma Mitochondrial DNA--a Novel DAMP in Pediatric Sepsis.

PubMed

Di Caro, Valentina; Walko, Thomas D; Bola, R Aaron; Hong, John D; Pang, Diana; Hsue, Victor; Au, Alicia K; Halstead, E Scott; Carcillo, Joseph A; Clark, Robert S B; Aneja, Rajesh K

2016-05-01

Mitochondrial DNA (mtDNA) is a novel danger-associated molecular pattern that on its release into the extracellular milieu acts via toll-like receptor-9, a pattern recognition receptor of the immune system. We hypothesized that plasma mtDNA concentrations will be elevated in septic children, and these elevations are associated with an increase in the severity of illness. In a separate set of in vitro experiments, we test the hypothesis that exposing peripheral blood mononuclear cells (PBMC) to mtDNA activates the immune response and induces tumor necrosis factor (TNF) release. Children with sepsis/systemic inflammatory response syndrome or control groups were enrolled within 24  h of admission to the pediatric intensive care unit. Mitochondrial gene cytochrome c oxidase 1 (COX1) concentrations were measured by real-time quantitative PCR in the DNA extracted from plasma. PBMCs were treated with mtDNA (10  μg/mL) and supernatant TNF levels were measured. The median plasma mtDNA concentrations were significantly elevated in the septic patients as compared with the critically ill non-septic and healthy control patients [1.75E+05 (IQR 6.64E+04-3.67E+05) versus 5.73E+03 (IQR 3.90E+03-1.28E+04) and 6.64E+03 (IQR 5.22E+03-1.63E+04) copies/μL respectively]. The median concentrations of plasma mtDNA were significantly greater in patients with MOF as compared with patients without MOF (3.2E+05 (IQR 1.41E+05-1.08E+06) vs. 2.9E+04 (IQR 2.47E+04-5.43E+04) copies/μL). PBMCs treated with mtDNA demonstrated higher supernatant TNF levels as compared with control cells (6.5 ± 1.8 vs. 3.5 ± 0.5  pg/mL, P > 0.05). Our data suggest that plasma mtDNA is a novel danger-associated molecular pattern in pediatric sepsis and appears to be associated with MOF.

Vaccination prepartum enhances the beneficial effects of melatonin on the immune response and reduces platelet responsiveness in sheep

PubMed Central

2012-01-01

Background Melatonin regulates several physiological processes and its powerful action as antioxidant has been widely reported. Melatonin acts modulating the immune system, showing a protective effect on the cardiovascular system and improving vaccine administration as an adjuvant-like agent. Here, we have investigated the role of melatonin as an adjuvant of the Clostridium perfringens vaccine in prepartum sheep and whether melatonin modulates platelet physiology during peripartum. Results The experiments were carried out in peripartum sheep from a farm located in an area of Mediterranean-type ecosystem. Plasma melatonin levels were determined by ELISA and sheep platelet aggregation was monitored using an aggregometer. Here we demonstrated for the first time that plasma melatonin concentration were higher in pregnant (125 pg/mL) than in non-pregnant sheep (15 pg/mL; P < 0.05). Administration of melatonin prepartum did not significantly modify platelet function but significantly improved the immune response to vaccination against C. perfringens. Conclusion Administration of melatonin as an adjuvant provides a significant improvement in the immune response to vaccine administration prepartum against C. perfringens. PMID:22716226

Transmethylation of homocysteine to methionine: efficiency in the rat and chick.

PubMed

Baker, D H; Czarnecki, G L

1985-10-01

Experiments were conducted with young chicks and rats to quantify the efficacy of L-homocysteine as a methionine precursor. Linear growth responses were obtained to both L-methionine and L-homocysteine when added to a methionine-deficient intact-protein diet containing a plethora of cystine. Slope-ratio multiple regression methodology indicated L-homocysteine to be 64.5% as efficacious as L-methionine in rats and 62.5% as efficacious in chicks. Plasma-free methionine also increased linearly as graded levels of either L-methionine or L-homocysteine were added to the diet of rats. At higher dosages of L-homocysteine, betaine, but not choline, showed some efficacy in enhancing the conversion of homocysteine to methionine. In the linear response surface of the growth curve, however, supplemental betaine was without effect on L-homocysteine bioefficacy, as was also the case for supplemental sarcosine and N5-methyltetrahydrofolic acid.

HIV-1 Nef and Vpu Interfere with L-Selectin (CD62L) Cell Surface Expression To Inhibit Adhesion and Signaling in Infected CD4+ T Lymphocytes

PubMed Central

Vassena, Lia; Giuliani, Erica; Koppensteiner, Herwig; Bolduan, Sebastian; Schindler, Michael

2015-01-01

ABSTRACT Leukocyte recirculation between blood and lymphoid tissues is required for the generation and maintenance of immune responses against pathogens and is crucially controlled by the L-selectin (CD62L) leukocyte homing receptor. CD62L has adhesion and signaling functions and initiates the capture and rolling on the vascular endothelium of cells entering peripheral lymph nodes. This study reveals that CD62L is strongly downregulated on primary CD4+ T lymphocytes upon infection with human immunodeficiency virus type 1 (HIV-1). Reduced cell surface CD62L expression was attributable to the Nef and Vpu viral proteins and not due to increased shedding via matrix metalloproteases. Both Nef and Vpu associated with and sequestered CD62L in perinuclear compartments, thereby impeding CD62L transport to the plasma membrane. In addition, Nef decreased total CD62L protein levels. Importantly, infection with wild-type, but not Nef- and Vpu-deficient, HIV-1 inhibited the capacity of primary CD4+ T lymphocytes to adhere to immobilized fibronectin in response to CD62L ligation. Moreover, HIV-1 infection impaired the signaling pathways and costimulatory signals triggered in primary CD4+ T cells by CD62L ligation. We propose that HIV-1 dysregulates CD62L expression to interfere with the trafficking and activation of infected T cells. Altogether, this novel HIV-1 function could contribute to virus dissemination and evasion of host immune responses. IMPORTANCE L-selectin (CD62L) is an adhesion molecule that mediates the first steps of leukocyte homing to peripheral lymph nodes, thus crucially controlling the initiation and maintenance of immune responses to pathogens. Here, we report that CD62L is downmodulated on the surfaces of HIV-1-infected T cells through the activities of two viral proteins, Nef and Vpu, that prevent newly synthesized CD62L molecules from reaching the plasma membrane. We provide evidence that CD62L downregulation on HIV-1-infected primary T cells results in impaired adhesion and signaling functions upon CD62L triggering. Removal of cell surface CD62L may predictably keep HIV-1-infected cells away from lymph nodes, the privileged sites of both viral replication and immune response activation, with important consequences, such as systemic viral spread and evasion of host immune surveillance. Altogether, we propose that Nef- and Vpu-mediated subversion of CD62L function could represent a novel determinant of HIV-1 pathogenesis. PMID:25822027

A dose-response effect from chocolate consumption on plasma epicatechin and oxidative damage.

PubMed

Wang, J F; Schramm, D D; Holt, R R; Ensunsa, J L; Fraga, C G; Schmitz, H H; Keen, C L

2000-08-01

Evidence from epidemiological studies suggests that a diet high in plant foods and rich in polyphenols is inversely associated with a risk for cardiovascular and other chronic diseases. Chocolate, like red wine and green tea, is a polyphenol-rich food, primarily containing procyanidin polyphenols. These polyphenols are hypothesized to provide cardioprotective effects due to their ability to scavenge free radicals and inhibit lipid oxidation. Herein, we demonstrate that 2 h after the ingestion of a procyanidin-rich chocolate containing 5.3 mg total procyanidin/g, of which 1.3 mg/g was (-)-epicatechin (epicatechin), plasma levels of epicatechin increased 133 +/- 27, 258 +/- 29 and 355 +/- 49 nmol/L in individuals who consumed 27, 53 and 80 g of chocolate, respectively. That the rise in plasma epicatechin levels was functionally significant is suggested by observations of trends for dose-response increases in the plasma antioxidant capacity and decreases in plasma lipid oxidation products. The above data support the theories that in healthy adults, 1) a positive relationship exists between procyanidin consumption and plasma procyanidin concentration and 2) the rise in plasma epicatechin contributes to the ability of plasma to scavenge free radicals and to inhibit lipid peroxidation.

The acute effects of L-arginine on hormonal and metabolic responses during submaximal exercise in trained cyclists.

PubMed

Forbes, Scott C; Harber, Vicki; Bell, Gordon J

2013-08-01

L-arginine may enhance endurance performance mediated by two primary mechanisms including enhanced secretion of endogenous growth hormone (GH) and as a precursor of nitric oxide (NO); however, research in trained participants has been equivocal. The purpose was to investigate the effect of acute L-arginine ingestion on the hormonal and metabolic response during submaximal exercise in trained cyclists. Fifteen aerobically trained men (age: 28 ± 5 y; body mass: 77.4 ± 9.5 kg; height: 180.9 ± 7.9 cm; VO2max: 59.6 ± 5.9 ml·kg- 1·min-1) participated in a randomized, double-blind, crossover study. Subjects consumed L-arginine (ARG; 0. 075 g·kg-1 body mass) or a placebo (PLA) before performing an acute bout of submaximal exercise (60 min at 80% of power output achieved at ventilatory threshold). The ARG condition significantly increased plasma L-arginine concentrations (~146%), while no change was detected in the PLA condition. There were no differences between conditions for GH, nonesterified fatty acids (NEFA), lactate, glucose, VO2, VCO2, RER, CHO oxidation, and NOx. There was reduced fat oxidation at the start of exercise (ARG: 0.36 ± 0.25 vs. PLA: 0.42 ± 0.23 g·min-1, p < .05) and an elevated plasma glycerol concentrations at the 45-min time point (ARG: 340.3 vs. PLA: 288.5 μmol·L-1, p < .05) after L-arginine consumption. In conclusion, the acute ingestion of L-arginine did not alter any hormonal, metabolic, or cardio-respiratory responses during submaximal exercise except for a small but significant increase in glycerol at the 45-min time point and a reduction in fat oxidation at the start of exercise.

Basal and glucagon-stimulated plasma C-peptide concentrations in healthy dogs, dogs with diabetes mellitus, and dogs with hyperadrenocorticism.

PubMed

Montgomery, T M; Nelson, R W; Feldman, E C; Robertson, K; Polonsky, K S

1996-01-01

Serum glucose and plasma C-peptide response to i.v. glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5, 10, 20, 30, and (for healthy dogs) 60 minutes after i.v. administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after i.v. glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after i.v. glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sampling times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .00l) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .01) in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, > 0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with the results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired beta-cell function (ie, diabetes mellitus), and dogs with increased beta-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of beta-cell loss in dogs with type-1 diabetes.

Synthesis and application of molecularly imprinted nanoparticles combined ultrasonic assisted for highly selective solid phase extraction trace amount of celecoxib from human plasma samples using design expert (DXB) software.

PubMed

Arabi, Maryam; Ghaedi, Mehrorang; Ostovan, Abbas; Tashkhourian, Javad; Asadallahzadeh, Hamideh

2016-11-01

In this work molecular imprinted nanoparticles (MINPs) was synthesized and applied for ultrasonic assisted solid phase extraction of celecoxib (CEL) from human plasma sample following its combination by HPLC-UV. The MINPs were prepared in a non-covalent approach using methacrylic acid as monomer, CEL as template, ethylene glycol dimethacrylate as cross-linker, and 2,2-azobisisobutyronitrile (AIBN) as the initiator of polymerization. pH, volume of rinsing and eluent solvent and amount of sorbent influence on response were investigated using factorial experimental design, while optimum point was achieved and set as 250mg sorbent, pH 7.0, 1.5mL washing solvent and 2mL eluent by analysis of results according to design expert (DX) software. At above specified conditions, CEL in human plasma with complicated matrices with acceptable high recoveries (96%) and RSD% lower than 10% was quantified and estimated. The proposed MISPE-HPLC-UV method has linear responses among peak area and concentrations of CEL in the range of 0.2-2000μgL(-1), with regression coefficient of 0.98. The limit of detection (LOD) and quantification (LOQ) based on three and ten times of the noise of HPLC peaks correspond to blank solution were 0.08 and 0.18μgL(-1), respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of acute and chronic treadmill exercise on rat plasma lactate and brain NPY, L-ENK, DYN A1-13.

PubMed

Chen, Jia-Xu; Zhao, Xin; Yue, Guang-Xin; Wang, Zhu-Feng

2007-02-01

This study was designed to investigate the effect of acute and chronic high-intensity treadmill exercise on changes in plasma lactate and brain neuropeptide (NPY), leucine-enkephalin (L-ENK), and dynorphin A(1-13) (DYN A(1-13)). Avidin-biotin complex (ABC) immunohistochemistry and image pattern analysis were used to observe the effect of chronic (total 7 weeks) and acute treadmill exercise (an initial speed of 15 m min(-1) gradually increased to 35 m min(-1) with 0 degrees, 20-25 min per day duration) on the changes of NPY, L-ENK, and DYN A(1-13) in different areas of rat brain. Plasma lactate was also measured in response to such exercise. Compared with preexercise control (P < 0.01), plasma lactate concentration significantly increased in the immediate postexercise; but it returned to the normal level soon after the 30 min postexercise. The content of NPY in paraventricular (PVN), dorsomedial (DMN), and ventromedial (VMN) hypothalamic nuclei continued to increase in 0, 30, and 180 min postexercise compared with preexercise control (P < 0.01). The content of L-ENK in caudate-putamen (CPu) significantly increased in the immediate postexercise compared with preexercise control (P < 0.01), but it gradually returned to the normal level after the 180 min postexercise. However, the content of DYN A(1-13) in PVN rose substantially only in 30 min postexercise in comparison with the preexercise control (P < 0.01). Thus, different changes of NPY, L-ENK, and DYN A(1-13) in response to such high-intensity exercise depend on the brain region and the time examined, especially, the contents of NPY in different brain regions continuously remain at a high level after such high-intensity exercise. And this high level might reduce energy expenditure and thus contribute to the stimulation of brain NPY neurons.

B-cell activation with CD40L or CpG measures the function of B-cell subsets and identifies specific defects in immunodeficient patients.

PubMed

Marasco, Emiliano; Farroni, Chiara; Cascioli, Simona; Marcellini, Valentina; Scarsella, Marco; Giorda, Ezio; Piano Mortari, Eva; Leonardi, Lucia; Scarselli, Alessia; Valentini, Diletta; Cancrini, Caterina; Duse, Marzia; Grimsholm, Ola; Carsetti, Rita

2017-01-01

Around 65% of primary immunodeficiencies are antibody deficiencies. Functional tests are useful tools to study B-cell functions in vitro. However, no accepted guidelines for performing and evaluating functional tests have been issued yet. Here, we report our experience on the study of B-cell functions in infancy and throughout childhood. We show that T-independent stimulation with CpG measures proliferation and differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. On the other hand, CD40L, a T-dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naïve and memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. The response to CD40L does not change with age. In patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Our results demonstrate that functional tests are an important tool to assess the functions of the humoral immune system. © 2016 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

NEU3 Sialidase Protein Interactors in the Plasma Membrane and in the Endosomes*

PubMed Central

Cirillo, Federica; Ghiroldi, Andrea; Fania, Chiara; Piccoli, Marco; Torretta, Enrica; Tettamanti, Guido; Gelfi, Cecilia; Anastasia, Luigi

2016-01-01

NEU3 sialidase has been shown to be a key player in many physio- and pathological processes, including cell differentiation, cellular response to hypoxic stress, and carcinogenesis. The enzyme, peculiarly localized on the outer leaflet of the plasma membrane, has been shown to be able to remove sialic acid residues from the gangliosides present on adjacent cells, thus creating cell to cell interactions. Nonetheless, herein we report that the enzyme localization is dynamically regulated between the plasma membrane and the endosomes, where a substantial amount of NEU3 is stored with low enzymatic activity. However, under opportune stimuli, NEU3 is shifted from the endosomes to the plasma membrane, where it greatly increases the sialidase activity. Finally, we found that NEU3 possesses also the ability to interact with specific proteins, many of which are different in each cell compartment. They were identified by mass spectrometry, and some selected ones were also confirmed by cross-immunoprecipitation with the enzyme, supporting NEU3 involvement in the cell stress response, protein folding, and intracellular trafficking. PMID:26987901

NEU3 Sialidase Protein Interactors in the Plasma Membrane and in the Endosomes.

PubMed

Cirillo, Federica; Ghiroldi, Andrea; Fania, Chiara; Piccoli, Marco; Torretta, Enrica; Tettamanti, Guido; Gelfi, Cecilia; Anastasia, Luigi

2016-05-13

NEU3 sialidase has been shown to be a key player in many physio- and pathological processes, including cell differentiation, cellular response to hypoxic stress, and carcinogenesis. The enzyme, peculiarly localized on the outer leaflet of the plasma membrane, has been shown to be able to remove sialic acid residues from the gangliosides present on adjacent cells, thus creating cell to cell interactions. Nonetheless, herein we report that the enzyme localization is dynamically regulated between the plasma membrane and the endosomes, where a substantial amount of NEU3 is stored with low enzymatic activity. However, under opportune stimuli, NEU3 is shifted from the endosomes to the plasma membrane, where it greatly increases the sialidase activity. Finally, we found that NEU3 possesses also the ability to interact with specific proteins, many of which are different in each cell compartment. They were identified by mass spectrometry, and some selected ones were also confirmed by cross-immunoprecipitation with the enzyme, supporting NEU3 involvement in the cell stress response, protein folding, and intracellular trafficking. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, L.; Nazikian, Raffi; Grierson, B. A.

Here, Resonant Magnetic Perturbations (RMPs) are a leading method for edge localized modes (ELMs) Control in fusion plasmas. However they can also cause a rapid degradation in energy confinement. In this paper we show that the energy confinement in low collisionality (v* e < 0.3) DIII-D ITER Similar Shape (ISS) plasmas often recovers after several energy confinement times for RMP amplitudes up to the threshold for ELM suppression. Immediately following the application of the RMP, the plasma stored energy decreases in proportion to the decrease in the line-averaged density during density "pump-out". Later in the discharge confinement recovery is observedmore » in the thermal ion channel and is correlated with the increase in the ion temperature at the top of the H-mode pedestal. A correlation between the inverse scale length of the ion temperature (α/L Ti) and the E x B shearing rate at the top of the pedestal is seen during the confinement recovery phase. Transport analysis reveals that the confinement improvement in the ion channel results from the self-similarity in the ion temperature profiles in the plasma core combined with the observed increase in α/L Ti in the plasma edge following density pump-out. In contrast the electron temperature scale length (α/L Ti) remains essentially unchanged in response to the application of the RMP. At significantly higher RMP levels the edge EXB shearing rate and α/L Ti does not increase and the confinement does not recover following density pump-out.« less

The effects of a lupin-enriched diet on oxidative stress and factors influencing vascular function in overweight subjects.

PubMed

Yang, Xingbin; Croft, Kevin D; Lee, Ya P; Mori, Trevor A; Puddey, Ian B; Sipsas, Sofia; Barden, Anne; Swinny, Ewald; Hodgson, Jonathan M

2010-11-15

A diet enriched in lupin kernel flour can lower blood pressure, but mechanisms responsible are unclear. Lupin is a source of polyphenols, protein, and L-arginine, factors that may influence blood pressure via effects on oxidative stress and vascular function. Therefore, we aimed to determine the effects of a lupin-enriched diet on oxidative stress and factors influencing vascular function as potential mechanisms for demonstrated benefits on blood pressure. Overweight men and women (n = 88) were recruited to a 16-week parallel-design study. Participants were randomly assigned to replace 15%-20% of their usual daily energy intake with white bread (control) or lupin kernel flour-enriched bread (lupin). All measurements were taken at baseline and 16 weeks. At baseline, plasma F₂-isoprostanes and 20-hydroxyeicosatetraenoic acid (20-HETE) were positively associated with blood pressure, and plasma nitrite was negatively associated with blood pressure (p < 0.05). For lupin relative to control, the estimated differences in plasma F₂-isoprostanes (45 pmol/L; 95%CI: -68, 158), urinary F₂-isoprostanes (17 pmol/mmol creatinine; 95%CI: -43, 76), plasma 20-HETE (75 pmol/L; 95%CI: -91, 241), and plasma nitrite (-0.3 μmol/L; 95%CI: -1.1, 0.4) were not significant. Although regular consumption of lupin-enriched bread can lower blood pressure, these results do not support for the hypothesis that this is via effects on oxidative stress or vascular function.

Plasma expansion into a waveguide created by a linearly polarized femtosecond laser pulse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lemos, N.; Grismayer, T.; Cardoso, L.

2013-06-15

We demonstrate the efficient generation of 4 mm and 8 mm long plasma waveguides in hydrogen and helium. These waveguides have matching spots sizes for 13 to 34 μm laser beams. The plasma waveguides are created by ultra-short laser pulses (sub-picosecond) of moderate intensities, ∼10{sup 15}–10{sup 16} W cm{sup −2}, that heat the plasma to initial temperatures of tens of eV in order to create a hot plasma column that will expand into a plasma waveguide. We have determined that the main heating mechanism when using fs laser pulses and plasma densities ∼10{sup 18–19} cm{sup −3} is Above Threshold Ionization.more » Detailed time and space electron density measurements are presented for the laser produced plasma waveguides.« less

Low-density lipoprotein electronegativity is a novel cardiometabolic risk factor.

PubMed

Hsu, Jing-Fang; Chou, Tzu-Chieh; Lu, Jonathan; Chen, Shu-Hua; Chen, Fang-Yu; Chen, Ching-Chu; Chen, Jeffrey L; Elayda, MacArthur; Ballantyne, Christie M; Shayani, Steven; Chen, Chu-Huang

2014-01-01

Low-density lipoprotein (LDL) plays a central role in cardiovascular disease (CVD) development. In LDL chromatographically resolved according to charge, the most electronegative subfraction-L5-is the only subfraction that induces atherogenic responses in cultured vascular cells. Furthermore, increasing evidence has shown that plasma L5 levels are elevated in individuals with high cardiovascular risk. We hypothesized that LDL electronegativity is a novel index for predicting CVD. In 30 asymptomatic individuals with metabolic syndrome (MetS) and 27 healthy control subjects, we examined correlations between plasma L5 levels and the number of MetS criteria fulfilled, CVD risk factors, and CVD risk according to the Framingham risk score. L5 levels were significantly higher in MetS subjects than in control subjects (21.9±18.7 mg/dL vs. 11.2±10.7 mg/dL, P:0.01). The Jonckheere trend test revealed that the percent L5 of total LDL (L5%) and L5 concentration increased with the number of MetS criteria (P<0.001). L5% correlated with classic CVD risk factors, including waist circumference, body mass index, waist-to-height ratio, smoking status, blood pressure, and levels of fasting plasma glucose, triglyceride, and high-density lipoprotein. Stepwise regression analysis revealed that fasting plasma glucose level and body mass index contributed to 28% of L5% variance. The L5 concentration was associated with CVD risk and contributed to 11% of 30-year general CVD risk variance when controlling the variance of waist circumference. Our findings show that LDL electronegativity was associated with multiple CVD risk factors and CVD risk, suggesting that the LDL electronegativity index may have the potential to be a novel index for predicting CVD. Large-scale clinical trials are warranted to test the reliability of this hypothesis and the clinical importance of the LDL electronegativity index.

Low-Density Lipoprotein Electronegativity Is a Novel Cardiometabolic Risk Factor

PubMed Central

Lu, Jonathan; Chen, Shu-Hua; Chen, Fang-Yu; Chen, Ching-Chu; Chen, Jeffrey L.; Elayda, MacArthur; Ballantyne, Christie M.; Shayani, Steven; Chen, Chu-Huang

2014-01-01

Background Low-density lipoprotein (LDL) plays a central role in cardiovascular disease (CVD) development. In LDL chromatographically resolved according to charge, the most electronegative subfraction–L5–is the only subfraction that induces atherogenic responses in cultured vascular cells. Furthermore, increasing evidence has shown that plasma L5 levels are elevated in individuals with high cardiovascular risk. We hypothesized that LDL electronegativity is a novel index for predicting CVD. Methods In 30 asymptomatic individuals with metabolic syndrome (MetS) and 27 healthy control subjects, we examined correlations between plasma L5 levels and the number of MetS criteria fulfilled, CVD risk factors, and CVD risk according to the Framingham risk score. Results L5 levels were significantly higher in MetS subjects than in control subjects (21.9±18.7 mg/dL vs. 11.2±10.7 mg/dL, P:0.01). The Jonckheere trend test revealed that the percent L5 of total LDL (L5%) and L5 concentration increased with the number of MetS criteria (P<0.001). L5% correlated with classic CVD risk factors, including waist circumference, body mass index, waist-to-height ratio, smoking status, blood pressure, and levels of fasting plasma glucose, triglyceride, and high-density lipoprotein. Stepwise regression analysis revealed that fasting plasma glucose level and body mass index contributed to 28% of L5% variance. The L5 concentration was associated with CVD risk and contributed to 11% of 30-year general CVD risk variance when controlling the variance of waist circumference. Conclusion Our findings show that LDL electronegativity was associated with multiple CVD risk factors and CVD risk, suggesting that the LDL electronegativity index may have the potential to be a novel index for predicting CVD. Large-scale clinical trials are warranted to test the reliability of this hypothesis and the clinical importance of the LDL electronegativity index. PMID:25203525

[Inhibitory effect of kukoamine B on lung inflammatory responses in mice with sepsis].

PubMed

Zhang, Jinli; Qin, Weiting; Lyu, Wanghui; Shen, Weichang; Wang, Xu; Sun, Bingwei

2014-07-01

To investigate the inhibitory effect of kukoamine B (KB) on lung inflammatory responses in mice with sepsis and its possible molecular mechanism. Twenty-eight male mice were randomly divided into control group (n=8), lipopolysaccharide (LPS) group (n=10), and LPS + KB group (n=10). Sepsis model was reproduced by intra-peritoneal injection of 20 mg/kg LPS, while equivalent normal saline was given in control group, and 20 μg/kg KB was injected through caudal vein 4 hours after LPS challenge in LPS + KB group. After 8 hours of LPS challenge, the concentration of LPS in plasma and the activity of myeloperoxidase (MPO) in the lung tissue were determined. The contents of tumor necrosis factor-α (TNF-α) and interleukin-1β(IL-1β) in plasma, alveolar lavage fluid and lung tissue homogenates were assessed by enzyme linked immunosorbent assay (ELISA). The activation of nuclear factor-ΚB (NF-ΚB) and the expression of inducible nitric oxide synthase (iNOS) in lung tissue were determined by Western Blot. The pathological changes in lung tissues were observed with hematoxylin-eosin (HE) staining. The expression of intercellular adhesion molecule-1 (ICAM-1) in lung tissue was determined by immunohistochemistry. Compared with control group, the concentration of LPS in plasma (1 155.650±147.149 kEU/L vs. 31.390±18.859 kEU/L), MPO activity (1.177±0.093 U/g vs. 0.775±0.166 U/g), NF-ΚB activity (gray value: 1.557±0.105 vs. 0.824±0.032) and the expression of iNOS (gray value: 0.650±0.129 vs. 0.392±0.097) were significantly increased in LPS group (all P<0.05). After KB intervention, the concentration of LPS (624.461±149.012 kEU/L), MPO activity (0.919±0.023 U/g), NF-ΚB activity (1.127±0.074) and the expression of iNOS (0.425±0.066) were significantly lowered (all P<0.05). Compared with control group, the contents of TNF-α (47.325±13.864 ng/L vs. 6.534±0.544 ng/L, 13.382±2.231 ng/L vs. 3.748±0.692 ng/L, 31.127±7.399 ng/L vs. 14.948±4.673 ng/L) and IL-1β (74.329±11.890 ng/L vs. 29.921±6.487 ng/L, 9.422±2.674 ng/L vs. 1.105±0.364 ng/L, 528.509±32.073 ng/L vs. 109.945±13.561 ng/L) in plasma, alveolar lavage fluid and lung tissue homogenates were obviously enhanced in LPS group (all P<0.05). With KB intervention, the contents of TNF-α (20.331±7.789 ng/L, 7.145±1.202 ng/L, 15.966±2.946 ng/L) and IL-1β (57.707±8.098 ng/L, 2.212±0.878 ng/L, 426.154±11.270 ng/L) were markedly reduced (plasma TNF-α: F=16.052, P=0.002; IL-1β: F=20.649, P=0.000; lung tissue homogenates TNF-α: F=31.134, P=0.001; IL-1β: F=22.792, P=0.002; alveolar lavage fluid TNF-α: F=10.013, P=0.009; IL-1β: F=319.857, P=0.000). In addition, leukocyte infiltration to the lung tissue was attenuated, and the expression of ICAM-1 was reduced by KB in histological examination. KB, as a neutralizer of LPS, can inhibit the release of inflammatory mediators, reduce the pulmonary inflammatory response and protect the function of lung in septic mice.

Acid-induced off-response of PKD2L1 channel in Xenopus oocytes and its regulation by Ca2+

PubMed Central

Hussein, Shaimaa; Zheng, Wang; Dyte, Chris; Wang, Qian; Yang, JungWoo; Zhang, Fan; Tang, Jingfeng; Cao, Ying; Chen, Xing-Zhen

2015-01-01

Polycystic kidney disease (PKD) protein 2 Like 1 (PKD2L1), also called transient receptor potential polycystin-3 (TRPP3), regulates Ca2+-dependent hedgehog signalling in primary cilia, intestinal development and sour tasting but with an unclear mechanism. PKD2L1 is a Ca2+-permeable cation channel that is activated by extracellular Ca2+ (on-response) in Xenopus oocytes. PKD2L1 co-expressed with PKD protein 1 Like 3 (PKD1L3) exhibits extracellular acid-induced activation (off-response, i.e., activation following acid removal) but whether PKD1L3 participates in acid sensing remains unclear. Here we used the two-microelectrode voltage-clamp, site directed mutagenesis, Western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence, and showed that PKD2L1 expressed in oocytes exhibits sustained off-response currents in the absence of PKD1L3. PKD1L3 co-expression augmented the PKD2L1 plasma membrane localization but did not alter the observed properties of the off-response. PKD2L1 off-response was inhibited by an increase in intracellular Ca2+. We also identified two intra-membrane residues aspartic acid 349 (D349) and glutamic acid 356 (E356) in the third transmembrane domain that are critical for PKD2L1 channel function. Our study suggests that PKD2L1 may itself sense acids and defines off-response properties in the absence of PKD1L3. PMID:26502994

The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males.

PubMed

Suzuki, Takashi; Morita, Masahiko; Hayashi, Toshio; Kamimura, Ayako

2017-02-01

We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.

Study of Laser Created Metal Vapour Plasmas.

DTIC Science & Technology

1981-09-01

ance saturation could lead to extensive ground Zcvei burnout of certain kinds of atoms or ions and that this could lead to the creation of a ground...level FORM DD I JAN ", 1473 UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PACE ’l hen Dota Fnt ’UNCLASSIFIFD SS ~eUItTY CLASSIFICATION OF THIS PAqE(W"Sef...vapours. Preliminary calculations have suggested that laser resonance saturation could lead to extensive ground level burnout of certain kinds of

Study of Laser Created Metal Vapor Plasmas.

DTIC Science & Technology

1979-11-16

Leventhal(1 indicate a value closer to 10-1 cm. might be expected. In the case of’ laser induced penniinf, ionization., wec -,;4-,rit LIP 32 LIP L J where...modified Kramer’s formulae.(25) In figure 11 we demonstrate the impact of associative ionization and laser induced penning ionization upon the temporal...34Laser Induced Fluorescence and Environmental Sensing", Invited paper for Optical Society of America, Topical Mcetixg on "Applications of Laser

Particle Acceleration, Magnetic Field Generation, and Emission in Relativistic Pair Jets

NASA Technical Reports Server (NTRS)

Nishikawa, K. I.; Hardee, P.; Hededal, C. B.; Richardson, G.; Sol, H.; Preece, R.; Fishman, G. J.

2004-01-01

Shock acceleration is a ubiquitous phenomenon in astrophysical plasmas. Plasma waves and their associated instabilities (e.g., Buneman, Weibel and other two-stream instabilities) created in collisionless shocks are responsible for particle (electron, positron, and ion) acceleration. Using a 3-D relativistic electromagnetic particle (REMP) code, we have investigated particle acceleration associated with a relativistic jet front propagating into an ambient plasma. We find that the growth times depend on the Lorenz factors of jets. The jets with larger Lorenz factors grow slower. Simulations show that the Weibel instability created in the collisionless shock front accelerates jet and ambient particles both perpendicular and parallel to the jet propagation direction. The small scale magnetic field structure generated by the Weibel instability is appropriate to the generation of "jitter" radiation from deflected electrons (positrons) as opposed to synchrotron radiation. The jitter radiation resulting from small scale magnetic field structures may be important for understanding the complex time structure and spectral evolution observed in gamma-ray bursts or other astrophysical sources containing relativistic jets and relativistic collisionless shocks.

Effect of starch ingestion on plasma glutamate concentrations in humans ingesting monosodium L-glutamate in soup.

PubMed

Stegink, L D; Filer, L J; Baker, G L

1985-02-01

Plasma glutamate concentrations in human subjects are markedly lower when monosodium L-glutamate is ingested in a water solution containing partially hydrolyzed starch than when ingested in water alone. This study was carried out to investigate whether starch ingested as crackers had a similar effect. Eight normal adult subjects (four male, four female) ingested three servings of a beef consommé providing 50 mg/kg body weight monosodium L-glutamate. One serving was consommé alone, the other two were accompanied by sufficient crackers to provide 0.25 or 0.5 g starch per kilogram body weight, respectively. Ingestion of consommé containing glutamate significantly increased the mean plasma glutamate concentration above baseline to a mean peak value 30 min later. The peak after consumption of 0.5 g starch per kilogram body weight, but not 0.25 g/kg body weight, was significantly lower than when consommé alone was ingested. These data indicate that simultaneous ingestion of metabolizable carbohydrate with glutamate has a marked effect on the plasma glutamate response and indicate that the threshold value for carbohydrate is greater than 0.25 g/kg body weight.

Comparing simulation of plasma turbulence with experiment. II. Gyrokinetic simulations

NASA Astrophysics Data System (ADS)

Ross, David W.; Dorland, William

2002-12-01

The direct quantitative correspondence between theoretical predictions and the measured plasma fluctuations and transport is tested by performing nonlinear gyrokinetic simulations with the GS2 code. This is a continuation of previous work with gyrofluid simulations [D. W. Ross et al., Phys. Plasmas 9, 177 (2002)], and the same L-mode reference discharge in the DIII-D tokamak [J. L. Luxon and L. G. Davis, Fusion Technol. 8, 441 (1985)] is studied. The simulated turbulence is dominated by ion temperature gradient (ITG) modes, corrected by trapped-electron, passing-electron and impurity effects. The energy fluxes obtained in the gyrokinetic simulations are comparable to, even somewhat higher than, those of the earlier work, and the simulated ion thermal transport, corrected for E×B flow shear, exceeds the experimental value by more than a factor of 2. The simulation also overestimates the density fluctuation level. Varying the local temperature gradient shows a stiff response in the flux and an apparent up-shift from the linear mode threshold [A. M. Dimits et al., Phys. Plasmas 7, 969 (2000)]. This effect is insufficient, within the estimated error, to bring the results into conformity with the experiment.

[The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome].

PubMed

Cui, Jia; Dou, Jingtao; Yang, Guoqing; Zang, Li; Jin, Nan; Chen, Kang; Du, Jin; Gu, Weijun; Wang, Xianling; Yang, Lijuan; Lyu, Zhaohui; Ba, Jianming; Mu, Yiming; Lu, Juming; Li, Jiangyuan; Pan, Changyu

2015-07-01

Cushing's syndrome is a clinical condition resulting from chronic exposure to excess glucocorticoid. As a consequence, long-term hypercortisolism contributes significantly to the development of systemic disorders by direct and/or indirect effects. The present study was to analyze the changes of renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome on the standard posture test. We retrospectively reviewed 150 patients with histologically confirmed Cushing's syndrome treated at the PLA General Hospital between 2002 and 2014. Among them, 128 patients were diagnosed as adreno-cortico-tropic-hormone (ACTH)-independent Cushing's syndrome, and 22 were ACTH-dependent Cushing's syndrome. All patients were undertaken the posture test. Plasma renin activity (PRA), angiotensin II, plasma aldosterone concertration (PAC) levels were measured before and after the test. Basal plasma PRA [0.5 (0.2,1.3)µg·L(-1)·h(-1), angiotensin II [(48.9±20.1) ng/L] and PAC [(285.0±128.1) pmol/L] levels were within the normal range in supine position. Compared with the subjects with ACTH-independent Cushing's syndrome, the basal PAC levels were higher in subjects with ACTH-dependent Cushing's syndrome [(348.0±130.4) pmol/L vs (274.2±125.0) pmol/L, P<0.05]. However, the PAC response in subjects with ACTH-dependent Cushing's syndrome [(49.7±26.4)%] was significantly lower than that in those with ACTH-independent Cushing's syndrome [(81.2±69.3)%] upon upright posture stimulation (P<0.05). There were no statistical significances in PRA and angiotensin II levels between the two groups. The basal PAC and PRA levels were positively correlated with ACTH, whereas PAC response was negatively correlated with ACTH. The renin-angiotensin-aldosterone-system activity in subjects with Cushing's syndrome was similar to that in normal control. The basal PAC level and its response to upright posture are differently associated with ACTH level in Cushing's syndrome.

Nanotribological response of a plasma nitrided bio-steel.

PubMed

Samanta, Aniruddha; Chakraborty, Himel; Bhattacharya, Manjima; Ghosh, Jiten; Sreemany, Monjoy; Bysakh, Sandip; Rane, Ramkrishna; Joseph, Alphonsa; Jhala, Ghanshyam; Mukherjee, Subroto; Das, Mitun; Mukhopadhyay, Anoop K

2017-01-01

AISI 316L is a well known biocompatible, austenitic stainless steel (SS). It is thus a bio-steel. Considering its importance as a bio-prosthesis material here we report the plasma nitriding of AISI 316L (SS) followed by its microstructural and nanotribological characterization. Plasma nitriding of the SS samples was carried out in a plasma reactor with a hot wall vacuum chamber. For ease of comparison these plasma nitrided samples were termed as SSPN. The experimental results confirmed the formations of an embedded nitrided metal layer zone (ENMLZ) and an interface zone (IZ) between the ENMLZ and the unnitrided bulk metallic layer zone (BMLZ) in the SSPN sample. These ENMLZ and IZ in the SSPN sample were richer in iron nitride (FeN) chromium nitride (CrN) along with the austenite phase. The results from nanoindentation, microscratch, nanoscratch and sliding wear studies confirmed that the static contact deformation resistance, the microwear, nanowear and sliding wear resistance of the SSPN samples were much better than those of the SS samples. These results were explained in terms of structure-property correlations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Elvitegravir concentrations in seminal plasma in HIV-1-infected men.

PubMed

Imaz, A; Niubó, J; Kashuba, A D; Ferrer, E; Sykes, C; Rozas, N; Acerete, L; Vila, A; Podzamczer, D

2017-03-01

The aim of the study was to quantify elvitegravir (EVG) concentrations in the semen of HIV-1-infected men receiving antiretroviral therapy (ART) consisting of an elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) single-tablet regimen. A phase IV, cross-sectional study was carried out including HIV-1-infected male adults with suppressed plasma HIV-1 RNA who switched ART to EVG/COBI/FTC/TDF. Total EVG concentrations at the end of the dosing interval (C 24 h ) and HIV-1 RNA were measured in paired seminal plasma (SP) and blood plasma (BP) samples 4 weeks after switching to EVG/COBI/FTC/TDF. Validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify EVG concentrations, and HIV-1 RNA was determined by real-time polymerase chain reaction (PCR). Ten men were included. Their median age was 40 years (range 24-47 years), the median time on ART was 50 months (range 10-186 months), the median time with plasma HIV-1 RNA < 40 copies/mL was 37 months (range 7-113 months), and the median CD4 count was 737 cells/μL (range 190-1122 cells/μL). Four weeks after switching to EVG/COBI/FTC/TDF, all subjects had HIV-1 RNA < 40 copies/mL in both BP and SP. Median EVG C 24 h was 277 ng/mL (range 64.8-1790 ng/mL) in BP and 169 ng/mL (range 12.8-792 ng/mL) in SP. A significant correlation was observed between BP and SP EVG concentrations (Spearman rho 0.952; P < 0.001). The median SP:BP EVG concentration ratio was 0.39 (range 0.20-0.92). EVG C 24 h in SP was at least 23-fold the in vitro protein-unbound 50% effective response (EC 50 ) of HIV-1 clinical isolates (0.04-0.55 ng/mL). In all but one individual, EVG C 24 h in SP was also higher than the blood plasma protein binding-adjusted 95% inhibitory concentration (IC 95 ) of wild-type HIV-1 (45 ng/mL). Seminal EVG concentrations in HIV-infected men treated with EVG/COBI/FTC/TDF sufficed to contribute to maintaining HIV-1 RNA suppression in this compartment. © 2016 British HIV Association.

Cumulative plasma HIV burden disparities among adults in HIV care: implications for HIV transmission in the era of treatment as prevention.

PubMed

Hughes, Alison J; Rector, Amadeia; Jimenez, Veronica; Brock, Jon; Scheer, Susan

2018-06-11

To characterize disparities in cumulative plasma HIV burden in a sample of adults accessing HIV care in San Francisco, California. Observational cohort and supplemental HIV surveillance data. Data from the San Francisco Medical Monitoring Project 2012-2014 cycles and HIV surveillance data were used to create an analytic cohort followed for two years. Matched HIV viral load (VL) test results from HIV surveillance were used to create five viral outcome measures: any unsuppressed VL (>200 copies/mL), any transmittable VL (>1500 copies/mL), person-time spent unsuppressed, person-time spent transmittable, and 2-year viremia copy-years, a measure of cumulative plasma HIV burden. Rao-Scott chi-squares and ANOVA examined differences in durable suppression and mean percent time spent unsuppressed and transmittable. Weighted linear regression was used to describe differences in cumulative HIV burden. Adults receiving HIV care spent approximately 12% of the 2-year time period with an unsuppressed viral load and approximately 7% of the time at a transmittable viral level. Factors independently associated with higher cumulative HIV viremia in an adjusted model included trans female identity, younger age, lower CD4 count, and a history of homelessness, incarceration, not taking ART, and non-adherence to ART. Although 95% of the cohort of adults in HIV care in San Francisco self-reported ART use during MMP interview, they spent on average almost one month per year at a transmittable viral level. We identified characteristics of those who were more likely to have higher viral burden, highlighting priorities for resource allocation to reduce onward HIV transmission.

A Comparative Study for Detection of EGFR Mutations in Plasma Cell-Free DNA in Korean Clinical Diagnostic Laboratories

PubMed Central

2018-01-01

Liquid biopsies to genotype the epidermal growth factor receptor (EGFR) for targeted therapy have been implemented in clinical decision-making in the field of lung cancer, but harmonization of detection methods is still scarce among clinical laboratories. We performed a pilot external quality assurance (EQA) scheme to harmonize circulating tumor DNA testing among laboratories. For EQA, we created materials containing different levels of spiked cell-free DNA (cfDNA) in normal plasma. The limit of detection (LOD) of the cobas® EGFR Mutation Test v2 (Roche Molecular Systems) was also evaluated. From November 2016 to June 2017, seven clinical diagnostic laboratories participated in the EQA program. The majority (98.94%) of results obtained using the cobas assay and next-generation sequencing (NGS) were acceptable. Quantitative results from the cobas assay were positively correlated with allele frequencies derived from digital droplet PCR measurements and showed good reproducibility among laboratories. The LOD of the cobas assay was 5~27 copies/mL for p.E746_A750del (exon 19 deletion), 35~70 copies/mL for p.L858R, 18~36 copies/mL for p.T790M, and 15~31 copies/mL for p.A767_V769dup (exon 20 insertion). Deep sequencing of materials (>100,000X depth of coverage) resulted in detection of low-level targets present at frequencies of 0.06~0.13%. Our results indicate that the cobas assay is a reliable and rapid method for detecting EGFR mutations in plasma cfDNA. Careful interpretation is particularly important for p.T790M detection in the setting of relapse. Individual laboratories should optimize NGS performance to maximize clinical utility.

Reverse Current Shock Induced by Plasma-Neutral Collision

NASA Astrophysics Data System (ADS)

Wongwaitayakornkul, Pakorn; Haw, Magnus; Li, Hui; Li, Shengtai; Bellan, Paul

2017-10-01

The Caltech solar experiment creates an arched plasma-filled flux rope expanding into low density background plasma. A layer of electrical current flowing in the opposite direction with respect to the flux rope current is induced in the background plasma just ahead of the flux rope. Two dimensional spatial and temporal measurements by a 3-dimensional magnetic vector probe demonstrate the existence of this induced current layer forming ahead of the flux rope. The induced current magnitude is 20% of the magnitude of the current in the flux rope. The reverse current in the low density background plasma is thought to be a diamagnetic response that shields out the magnetic field ahead of the propagation. The spatial and magnetic characteristics of the reverse current layer are consistent with similar shock structures seen in 3-dimensional ideal MHD numerical simulations performed on the Turquoise supercomputer cluster using the Los Alamos COMPutational Astrophysics Simulation Suite. This discovery of the induced diamagnetic current provides useful insights for space and solar plasma.

Real-time interferometric diagnostics of rubidium plasma

NASA Astrophysics Data System (ADS)

Djotyan, G. P.; Bakos, J. S.; Kedves, M. Á.; Ráczkevi, B.; Dzsotjan, D.; Varga-Umbrich, K.; Sörlei, Zs.; Szigeti, J.; Ignácz, P.; Lévai, P.; Czitrovszky, A.; Nagy, A.; Dombi, P.; Rácz, P.

2018-03-01

A method of interferometric real-time diagnostics is developed and applied to rubidium plasma created by strong laser pulses in the femtosecond duration range at different initial rubidium vapor densities using a Michelson-type interferometer. A cosine fit with an exponentially decaying relative phase is applied to the obtained time-dependent interferometry signals to measure the density-length product of the created plasma and its recombination time constant. The presented technique may be applicable for real-time measurements of rubidium plasma dynamics in the AWAKE experiment at CERN, as well as for real-time diagnostics of plasmas created in different gaseous media and on surfaces of solid targets.

Effects of plane of nutrition and 2,4-thiazolidinedione on insulin responses and adipose tissue gene expression in dairy cattle during late gestation.

PubMed

Schoenberg, K M; Overton, T R

2011-12-01

Specific mechanisms by which dry period dietary energy affects transition cow metabolism have been intensively investigated but those of thiazolidinedione (TZD) administration have not. We hypothesized that effects of both are mediated via changes in insulin, glucose, or fatty acid metabolism. The objective of this experiment was to determine the effects of the insulin-sensitizing agent TZD and dietary energy level on glucose and fatty acid metabolism during late gestation in dairy cows. Multiparous Holstein cows (n=32) approximately 50 d before expected calving date were dried-off and assigned to 1 of 2 dietary energy levels for 3 wk (high: 1.52 Mcal/kg of NE(L), or low: 1.34 Mcal/kg of NE(L)) and treated daily during the final 14 d with 4.0 mg of TZD/kg of body weight (BW) or saline in a completely randomized design. Cows fed the low energy diet had lower dry matter intake (12.8 vs. 16.1 kg/d) and higher plasma nonesterified fatty acid (NEFA) concentrations (103.3 vs. 82.4 μEq/L) compared with cows fed the high energy diet. Cows administered TZD had higher plasma glucose concentrations (62.5 vs. 59.6 mg/dL) than saline controls and cows fed the high energy diet had higher plasma insulin concentrations (35.1 vs. 25.3 μU/mL) compared with those fed the low energy diet. After 2 wk of TZD treatment, all cows were subjected to an intravenous glucose tolerance test (GTT; 0.25 g of dextrose/kg of BW) followed 110 min later by an insulin challenge (IC; 1.0 μg of insulin/kg of BW). Differences in plasma glucose response to GTT were minimal based on diet; however, cows fed the low energy diet had more negative NEFA areas under the curve (AUC; -4,838 vs. -2,137 μEq/L × min over 90 min) and greater rates of NEFA decrease (1.35 vs. 0.63%/min) during GTT, suggesting differential responses of tissue glucose and fatty acid metabolism in response to dietary energy level. During IC, the TZD-treated cows tended to have more negative glucose AUC (-45.0 vs. -12.1mg/dL × min over 15 min) than controls, suggesting that TZD-treated cows had greater responses to insulin. Limited interactions were observed between dietary and TZD treatments in all response variables measured. Adipose tissue biopsies performed on the final day of treatment suggested higher expression of peroxisome proliferator-activated receptor-γ (0.71 vs. 0.50 relative expression) and lipoprotein lipase (0.71 vs. 0.40 relative expression) in cows fed the high energy diet as measured by quantitative real-time PCR. These results indicate that energy level and insulin-sensitizing agents affect glucose and lipid metabolism during the dry period. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Turbulent transport stabilization by ICRH minority fast ions in low rotating JET ILW L-mode plasmas

NASA Astrophysics Data System (ADS)

Bonanomi, N.; Mantica, P.; Di Siena, A.; Delabie, E.; Giroud, C.; Johnson, T.; Lerche, E.; Menmuir, S.; Tsalas, M.; Van Eester, D.; Contributors, JET

2018-05-01

The first experimental demonstration that fast ion induced stabilization of thermal turbulent transport takes place also at low values of plasma toroidal rotation has been obtained in JET ILW (ITER-like wall) L-mode plasmas with high (3He)-D ICRH (ion cyclotron resonance heating) power. A reduction of the gyro-Bohm normalized ion heat flux and higher values of the normalized ion temperature gradient have been observed at high ICRH power and low NBI (neutral beam injection) power and plasma rotation. Gyrokinetic simulations indicate that ITG (ion temperature gradient) turbulence stabilization induced by the presence of high-energetic 3He ions is the key mechanism in order to explain the experimental observations. Two main mechanisms have been identified to be responsible for the turbulence stabilization: a linear electrostatic wave-fast particle resonance mechanism and a nonlinear electromagnetic mechanism. The dependence of the stabilization on the 3He distribution function has also been studied.

Determination of the anti-inflammatory and cytoprotective effects of l-glutamine and l-alanine, or dipeptide, supplementation in rats submitted to resistance exercise.

PubMed

Raizel, Raquel; Leite, Jaqueline Santos Moreira; Hypólito, Thaís Menezes; Coqueiro, Audrey Yule; Newsholme, Philip; Cruzat, Vinicius Fernandes; Tirapegui, Julio

2016-08-01

We evaluated the effects of chronic oral supplementation with l-glutamine and l-alanine in their free form or as the dipeptide l-alanyl-l-glutamine (DIP) on muscle damage, inflammation and cytoprotection, in rats submitted to progressive resistance exercise (RE). Wistar rats (n 8/group) were submitted to 8-week RE, which consisted of climbing a ladder with progressive loads. In the final 21 d before euthanasia, supplements were delivered in a 4 % solution in drinking water. Glutamine, creatine kinase (CK), lactate dehydrogenase (LDH), TNF-α, specific IL (IL-1β, IL-6 and IL-10) and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated in plasma. The concentrations of glutamine, TNF-α, IL-6 and IL-10, as well as NF-κB activation, were determined in extensor digitorum longus (EDL) skeletal muscle. HSP70 level was assayed in EDL and peripheral blood mononuclear cells (PBMC). RE reduced glutamine concentration in plasma and EDL (P<0·05 v. sedentary group). However, l-glutamine supplements (l-alanine plus l-glutamine (GLN+ALA) and DIP groups) restored glutamine levels in plasma (by 40 and 58 %, respectively) and muscle (by 93 and 105 %, respectively). GLN+ALA and DIP groups also exhibited increased level of HSP70 in EDL and PBMC, consistent with the reduction of NF-κB p65 activation and cytokines in EDL. Muscle protection was also indicated by attenuation in plasma levels of CK, LDH, TNF-α and IL-1β, as well as an increase in IL-6, IL-10 and MCP-1. Our study demonstrates that chronic oral l-glutamine treatment (given with l-alanine or as dipeptide) following progressive RE induces cyprotective effects mediated by HSP70-associated responses to muscle damage and inflammation.

Plasma Theory and Simulation.

DTIC Science & Technology

1978-07-01

l l) A paper t i t led “Part icle-Fluid Hybrid Codes Applied to Beam- Plasma , Ring -Plasma Instabi l i ties ” was presented at Monterey (see Section V...ic le-Fluid Hybr id Codes Applied to Beam- Plasma , Ring -Plasma Ins tab i l i t ies”. (2) A. Peiravi and C. K. Birdsall , “Self-Heating of id Therma l

Physiological response of juvenile rainbow trout to chronic low level exposures of waterborne silver.

PubMed

Galvez, F; Hogstrand, C; Wood, C M

1998-02-01

The physiological effects of chronic exposure to AgNO3 in moderately hard freshwater were investigated in juvenile rainbow trout (Oncorhynchus mykiss Walbaum). Two separate 28-day exposures were performed at silver concentrations of 0.5 and 2.0 micrograms/L in flowing Hamilton dechlorinated tap water. Exposure to 0.5 microgram/L Ag resulted in a slight increase (approximately 14.9%) in food consumption, whereas growth rates remained unaltered. Both plasma Na+ and Cl- levels were significantly decreased by 11.8% and 9.3%, respectively at day 16 of the exposure. Hepatic Ag concentrations were elevated approximately 4-fold in 0.5 microgram/L Ag-exposed fish. However, no significant increases in liver metallothionein (MT) concentrations were noted. No mortalities were observed during this 28-day exposure. In comparison, chronic exposure to 2.0 micrograms/L Ag resulted in a 28.8% decrease in food consumption and a 43.0% reduction in growth rate. Plasma [Na+] was decreased by 18.3%, whereas plasma [Cl-] was reduced by 12.2% at day 7. At both concentrations of silver, plasma ion concentrations appeared to recover thereafter. Silver accumulated steadily in the liver up until day 15 when concentrations were 39.7 micrograms/g wet weight (285-fold increase) above control levels. In addition, MT levels were increased by 81.2% at day 7. Silver exposure at 2.0 micrograms/L resulted in approximately 15.0% mortality over the 28-day period.

Treatment of Intestinal Helminths Does Not Reduce Plasma Concentrations of HIV-1 RNA in Coinfected Zambian Adults

PubMed Central

Modjarrad, Kayvon; Zulu, Isaac; Redden, David T.; Njobvu, Lungowe; Lane, H. Clifford; Bentwich, Zvi; Vermund, Sten H.

2009-01-01

Background Infection with intestinal helminths may stimulate dysfunctional immune responses in human immunodeficiency virus (HIV)–infected persons. Studies have yielded conflicting results regarding the impact of antihelminthic treatment on plasma concentrations of HIV-1 RNA. Methods We conducted a prospective study of 54 HIV-1– and helminth-coinfected and 57 HIV-1–infected, helminth-uninfected asymptomatic adults living in Lusaka, Zambia, to assess the impact of antihelminthic treatment on plasma concentrations of HIV-1 RNA. Results Median baseline viral load was 0.33 log10 copies/mL lower in the helminth-infected group than in the uninfected group. Mean viral load between pretreatment and posttreatment visits increased in the helminth-infected (mean, 4.23 vs. 4.29 log10 copies/mL; P = .6) and helminth-uninfected (mean, 4.39 vs. 4.52 log10 copies/mL; P = .2) groups. Helminth-infected participants with high pretreatment viral loads had a mean 0.25-log10 copies/mL decrease after treatment (P = .3), and helminth-uninfected participants had a mean 0.02-log10 copies/mL decrease (P = .8). Conclusions We did not find an overall association between treatment of intestinal helminth infections and reduction in viral load in coinfected adults. Future studies may need to focus on adults with intense helminth infections who live in rural areas or on adults or children who harbor higher helminth burdens and plasma concentrations of HIV-1 RNA. PMID:16136473

HIF and HOIL-1L-mediated PKCζ degradation stabilizes plasma membrane Na,K-ATPase to protect against hypoxia-induced lung injury.

PubMed

Magnani, Natalia D; Dada, Laura A; Queisser, Markus A; Brazee, Patricia L; Welch, Lynn C; Anekalla, Kishore R; Zhou, Guofei; Vagin, Olga; Misharin, Alexander V; Budinger, G R Scott; Iwai, Kazuhiro; Ciechanover, Aaron J; Sznajder, Jacob I

2017-11-21

Organisms have evolved adaptive mechanisms in response to stress for cellular survival. During acute hypoxic stress, cells down-regulate energy-consuming enzymes such as Na,K-ATPase. Within minutes of alveolar epithelial cell (AEC) exposure to hypoxia, protein kinase C zeta (PKCζ) phosphorylates the α 1 -Na,K-ATPase subunit and triggers it for endocytosis, independently of the hypoxia-inducible factor (HIF). However, the Na,K-ATPase activity is essential for cell homeostasis. HIF induces the heme-oxidized IRP2 ubiquitin ligase 1L (HOIL-1L), which leads to PKCζ degradation. Here we report a mechanism of prosurvival adaptation of AECs to prolonged hypoxia where PKCζ degradation allows plasma membrane Na,K-ATPase stabilization at ∼50% of normoxic levels, preventing its excessive down-regulation and cell death. Mice lacking HOIL-1L in lung epithelial cells ( Cre SPC /HOIL-1L fl/fl ) were sensitized to hypoxia because they express higher levels of PKCζ and, consequently, lower plasma membrane Na,K-ATPase levels, which increased cell death and worsened lung injury. In AECs, expression of an α 1 -Na,K-ATPase construct bearing an S18A (α 1 -S18A) mutation, which precludes PKCζ phosphorylation, stabilized the Na,K-ATPase at the plasma membrane and prevented hypoxia-induced cell death even in the absence of HOIL-1L. Adenoviral overexpression of the α 1 -S18A mutant Na,K-ATPase in vivo rescued the enhanced sensitivity of Cre SPC/ HOIL-1L fl/fl mice to hypoxic lung injury. These data suggest that stabilization of Na,K-ATPase during severe hypoxia is a HIF-dependent process involving PKCζ degradation. Accordingly, we provide evidence of an important adaptive mechanism to severe hypoxia, whereby halting the exaggerated down-regulation of plasma membrane Na,K-ATPase prevents cell death and lung injury.

Larval exposure to 4-nonylphenol and 17β-estradiol affects physiological and behavioral development of seawater adaptation in Atlantic salmon smolts

USGS Publications Warehouse

Lerner, Darrren T.; Bjornsson, Bjorn Thrandur; McCormick, Stephen D.

2007-01-01

Population declines of anadromous salmonids are attributed to anthropogenic disturbances including dams, commercial and recreational fisheries, and pollutants, such as estrogenic compounds. Nonylphenol (NP), a xenoestrogen, is widespread in the aquatic environment due to its use in agricultural, industrial, and household products. We exposed Atlantic salmon yolk-sac larvae to waterborne 10 or 100 μg L-1 NP (NP-L or NP-H, respectively), 2 μg L-1 17β-estradiol (E2), or vehicle, for 21 days to investigate their effects on smolt physiology and behavior 1 year later. NP-H caused approximately 50% mortality during exposure, 30 days after exposure, and 60 days after exposure. Mortality rates of NP-L and E2 fish were not affected until 60 days after treatment, when they were 4-fold greater than those of controls. Treatment with NP-L or E2 as yolk-sac larvae decreased gill sodium-potassium-activated adenosine triphosphatase (Na+,K+-ATPase) activity and seawater (SW) tolerance during smolt development, 1 year after exposure. Exposure to NP-L and E2 resulted in a latency to enter SW and reduced preference for SW approximately 2- and 5-fold, respectively. NP-L-exposed fish had 20% lower plasma insulin-like growth factor I (IGF-I) levels and 35% lower plasma triiodothyronine (T3). Plasma growth hormone and thyroxine (T4) were unaffected. Exposure to E2 did not affect plasma levels of IGF-I, GH, T3, or T4. Both treatment groups exhibited increased plasma cortisol and decreased osmoregulatory capacity in response to a handling stressor. These results suggest that early exposure to environmentally relevant concentrations of NP, and other estrogenic compounds, can cause direct and delayed mortalities and that this exposure can have long term, “organizational” effects on life-history events in salmonids.

Investigation of plasma-surface interaction effects on pulsed electrostatic manipulation for reentry blackout alleviation

NASA Astrophysics Data System (ADS)

Krishnamoorthy, S.; Close, S.

2017-03-01

The reentry blackout phenomenon affects most spacecraft entering a dense planetary atmosphere from space, due to the presence of a plasma layer that surrounds the spacecraft. This plasma layer is created by ionization of ambient air due to shock and frictional heating, and in some cases is further enhanced due to contamination by ablation products. This layer causes a strong attenuation of incoming and outgoing electromagnetic waves including those used for command and control, communication and telemetry over a period referred to as the ‘blackout period’. The blackout period may last up to several minutes and is a major contributor to the landing error ellipse at best, and a serious safety hazard in the worst case, especially in the context of human spaceflight. In this work, we present a possible method for alleviation of reentry blackout using electronegative DC pulses applied from insulated electrodes on the reentry vehicle’s surface. We study the reentry plasma’s interaction with a DC pulse using a particle-in-cell (PIC) model. Detailed models of plasma-insulator interaction are included in our simulations. The absorption and scattering of ions and electrons at the plasma-dielectric interface are taken into account. Secondary emission from the insulating surface is also considered, and its implications on various design issues is studied. Furthermore, we explore the effect of changing the applied voltage and the impact of surface physics on the creation and stabilization of communication windows. The primary aim of this analysis is to examine the possibility of restoring L- and S-band communication from the spacecraft to a ground station. Our results provide insight into the effect of key design variables on the response of the plasma to the applied voltage pulse. Simulations show the creation of pockets where electron density in the plasma layer is reduced three orders of magnitude or more in the vicinity of the electrodes. These pockets extend to distances up to three times the electrode length normal to the vehicle surface. Based on our results, we postulate that pulsed electrostatic manipulation (PEM) may be a viable candidate for reentry blackout alleviation in the future.

Protein corona formation in bronchoalveolar fluid enhances diesel exhaust nanoparticle uptake and pro-inflammatory responses in macrophages.

PubMed

Shaw, Catherine A; Mortimer, Gysell M; Deng, Zhou J; Carter, Edwin S; Connell, Shea P; Miller, Mark R; Duffin, Rodger; Newby, David E; Hadoke, Patrick W F; Minchin, Rodney F

2016-09-01

In biological fluids nanoparticles bind a range of molecules, particularly proteins, on their surface. The resulting protein corona influences biological activity and fate of nanoparticle in vivo. Corona composition is often determined by the biological milieu encountered at the entry portal into the body, and, can therefore, depend on the route of exposure to the nanoparticle. For environmental nanoparticles where exposure is by inhalation, this will be lung lining fluid. This study examined plasma and bronchoalveolar fluid (BALF) protein binding to engineered and environmental nanoparticles. We hypothesized that protein corona on nanoparticles would influence nanoparticle uptake and subsequent pro-inflammatory biological response in macrophages. All nanoparticles bound plasma and BALF proteins, but the profile of bound proteins varied between nanoparticles. Focusing on diesel exhaust nanoparticles (DENP), we identified proteins bound from plasma to include fibrinogen, and those bound from BALF to include albumin and surfactant proteins A and D. The presence on DENP of a plasma-derived corona or one of purified fibrinogen failed to evoke an inflammatory response in macrophages. However, coronae formed in BALF increased DENP uptake into macrophages two fold, and increased nanoparticulate carbon black (NanoCB) uptake fivefold. Furthermore, a BALF-derived corona increased IL-8 release from macrophages in response to DENP from 1720 ± 850 pg/mL to 5560 ± 1380 pg/mL (p = 0.014). These results demonstrate that the unique protein corona formed on nanoparticles plays an important role in determining biological reactivity and fate of nanoparticle in vivo. Importantly, these findings have implications for the mechanism of detrimental properties of environmental nanoparticles since the principle route of exposure to such particles is via the lung.

Effect of dietary cholesterol and plant sterol consumption on plasma lipid responsiveness and cholesterol trafficking in healthy individuals.

PubMed

Alphonse, Peter A S; Ramprasath, Vanu; Jones, Peter J H

2017-01-01

Dietary cholesterol and plant sterols differentially modulate cholesterol kinetics and circulating cholesterol. Understanding how healthy individuals with their inherent variabilities in cholesterol trafficking respond to such dietary sterols will aid in improving strategies for effective cholesterol lowering and alleviation of CVD risk. The objectives of this study were to assess plasma lipid responsiveness to dietary cholesterol v. plant sterol consumption, and to determine the response in rates of cholesterol absorption and synthesis to each sterol using stable isotope approaches in healthy individuals. A randomised, double-blinded, crossover, placebo-controlled clinical trial (n 49) with three treatment phases of 4-week duration were conducted in a Manitoba Hutterite population. During each phase, participants consumed one of the three treatments as a milkshake containing 600 mg/d dietary cholesterol, 2 g/d plant sterols or a control after breakfast meal. Plasma lipid profile was determined and cholesterol absorption and synthesis were measured by oral administration of [3, 4-13C] cholesterol and 2H-labelled water, respectively. Dietary cholesterol consumption increased total (0·16 (sem 0·06) mmol/l, P=0·0179) and HDL-cholesterol (0·08 (sem 0·03) mmol/l, P=0·0216) concentrations with no changes in cholesterol absorption or synthesis. Plant sterol consumption failed to reduce LDL-cholesterol concentrations despite showing a reduction (6 %, P=0·0004) in cholesterol absorption. An over-compensatory reciprocal increase in cholesterol synthesis (36 %, P=0·0026) corresponding to a small reduction in absorption was observed with plant sterol consumption, possibly resulting in reduced LDL-cholesterol lowering efficacy of plant sterols. These data suggest that inter-individual variability in cholesterol trafficking mechanisms may profoundly impact plasma lipid responses to dietary sterols in healthy individuals.

Metabolizable protein supply modulated the acute-phase response following vaccination of beef steers.

PubMed

Moriel, P; Arthington, J D

2013-12-01

Our objective was to evaluate the effects of MP supply, through RUP supplementation, on the acute-phase response of beef steers following vaccination. On d 0, Brangus-crossbred steers (n = 24; 173 ± 31 kg; 175 ± 16 d of age) were randomly assigned to receive 1 of 3 isocaloric diets formulated to provide 85, 100, and 115% of the daily MP requirements of a beef steer gaining 0.66 kg of BW daily. Diets were limit-fed at 1.8% of BW (DM basis) and individually provided to steers once daily (0800 h) from d 0 to 29. Steers were weighed on d 0 and 29, following a 12-h period of feed and water withdrawal. On d 7, steers were vaccinated against Mannheimia haemolytica (OneShot, Pfizer), and blood samples were collected on d 0, 7, 8, 10, 14, 21, and 30. Plasma metabolites were analyzed as repeated measures using the MIXED procedure of SAS. Final BW and ADG were similar (P ≥ 0.50) among treatments (mean = 184 ± 9 kg and 0.5 ± 0.08 kg/d, respectively). Effects of time were detected (P < 0.01) for plasma concentrations of all acute-phase proteins, which peaked between d 7 to 14, returning to baseline concentrations by d 29. Treatment effects were not detected (P ≥ 0.19) for plasma concentrations of acid-soluble protein, albumin, fibrinogen, IGF-1 and serum amyloid-A. Plasma concentrations of total protein (TP) and plasma urea nitrogen (PUN) increased (P ≤ 0.05) with increasing supply of MP (87.1, 89.6, and 90.1 ± 1.09 mg TP/mL and 6.1, 8.3, and 10.3 ± 0.41 mg PUN/dL for 85, 100, and 115% MP steers, respectively). From d 10 to 29, steers provided 115% MP had less (P < 0.001) plasma concentrations of ceruloplasmin than steers fed 85 and 100% MP, which had similar plasma ceruloplasmin concentrations. On d 14, plasma concentrations of haptoglobin were greatest (P ≤ 0.06) for steers fed 115% MP, intermediate for 100% MP, and least for 85% MP (0.98, 0.71 and 0.44 ± 0.099 mg/mL, respectively). On d 10, plasma concentrations of creatinine were greater (P = 0.01) for steers fed 115 vs. 85% MP, and intermediate for steers fed 100% MP (1.63, 1.28, and 1.50 ± 0.099 mg/dL, respectively). Thus, steers provided increasing metabolizable protein had greater plasma concentrations of haptoglobin, creatinine, total protein and PUN following vaccination against M. haemolytica.

Generation and Nuclear Translocation of Sumoylated Transmembrane Fragment of Cell Adhesion Molecule L1

PubMed Central

Lutz, David; Wolters-Eisfeld, Gerrit; Joshi, Gunjan; Djogo, Nevena; Jakovcevski, Igor; Schachner, Melitta; Kleene, Ralf

2012-01-01

The functions of the cell adhesion molecule L1 in the developing and adult nervous system are triggered by homophilic and heterophilic interactions that stimulate signal transductions that activate cellular responses. Here, we show that stimulation of signaling by function-triggering L1 antibodies or L1-Fc leads to serine protease-dependent cleavage of full-length L1 at the plasma membrane and generation of a sumoylated transmembrane 70-kDa fragment comprising the intracellular and transmembrane domains and part of the extracellular domain. The 70-kDa transmembrane fragment is transported from the plasma membrane to a late endosomal compartment, released from endosomal membranes into the cytoplasm, and transferred from there into the nucleus by a pathway that depends on importin and chromatin-modifying protein 1. Mutation of the sumoylation site at Lys1172 or of the nuclear localization signal at Lys1147 abolished L1-stimulated generation or nuclear import of the 70-kDa fragment, respectively. Nuclear import of the 70-kDa fragment may activate cellular responses in parallel or in association with phosphorylation-dependent signaling pathways. Alterations in the levels of the 70-kDa fragment during development and in the adult after spinal cord injury or in a mouse model of Alzheimer disease suggest that this fragment is functionally implicated in development, regeneration, neurodegeneration, tumorigenesis, and possibly synaptic plasticity in the mature nervous system. PMID:22431726

Changes in Stress and Appetite Responses in Male Power-Trained Athletes during Intensive Training Camp.

PubMed

Oshima, Satomi; Takehata, Chisato; Sasahara, Ikuko; Lee, Eunjae; Akama, Takao; Taguchi, Motoko

2017-08-21

An intensive consecutive high-volume training camp may induce appetite loss in athletes. Therefore, this study aimed to investigate the changes in stress and appetite responses in male power-trained athletes during an intensive training camp. The measurements at Day 2 and at the end of a 9-day intensive training camp (Camp1 and Camp2, respectively) were compared with those of the resting period (Rest) and the regular training period (Regular; n = 13). The stress state was assessed based on plasma cortisol level, salivary immunoglobulin A level, and a profile of mood states score. The sensation of appetite was assessed using visual analog scale scores, and fasting plasma acylated ghrelin, insulin, and glucose were measured. The cortisol concentrations were significantly higher at Camp2 (466.7 ± 60.7 nmol∙L -1 ) than at Rest (356.3 ± 100.9 nmol∙L -1 ; p = 0.002) or Regular (361.7 ± 111.4 nmol∙L -1 ; p = 0.003). Both prospective and actual food consumption significantly decreased at Camp2, and acylated ghrelin concentration was significantly lower at Camp1 (34.2 ± 8.0 pg∙mL -1 ) and Camp2 (32.0 ± 8.7 pg∙mL -1 ) than at Rest (47.2 ± 11.2 pg∙mL -1 ) or Regular (53.4 ± 12.6 pg∙mL -1 ). Furthermore, the change in acylated ghrelin level was negatively correlated with the change in cortisol concentration. This study's findings suggest that an early-phase physiological stress response may decrease the acylated ghrelin level in male power-trained athletes during an intensive training camp.

Impaired pancreatic polypeptide release in chronic pancreatitis with steatorrhoea.

PubMed

Adrian, T E; Besterman, H S; Mallinson, C N; Garalotis, C; Bloom, S R

1979-02-01

Pancreatic polypeptide (PP) is a newly discovered hormonal peptide localised in a distinct endocrine cell type in the pancreas. PP circulates in plasma and in normal subjects levels rise substantially on the ingestion of food (mean rise 138 pmol/l). In 10 patients with chronic pancreatitis with exocrine deficiency the PP response to a test breakfast was greatly reduced (mean rise 20 pmol/l, P less than 0.001). PP response to the meal was normal in 10 patients with active coeliac disease and 12 patients with acute tropical sprue with steatorrhoea.

Impaired pancreatic polypeptide release in chronic pancreatitis with steatorrhoea.

PubMed Central

Adrian, T E; Besterman, H S; Mallinson, C N; Garalotis, C; Bloom, S R

1979-01-01

Pancreatic polypeptide (PP) is a newly discovered hormonal peptide localised in a distinct endocrine cell type in the pancreas. PP circulates in plasma and in normal subjects levels rise substantially on the ingestion of food (mean rise 138 pmol/l). In 10 patients with chronic pancreatitis with exocrine deficiency the PP response to a test breakfast was greatly reduced (mean rise 20 pmol/l, P less than 0.001). PP response to the meal was normal in 10 patients with active coeliac disease and 12 patients with acute tropical sprue with steatorrhoea. PMID:428832

Effects of nonylphenol on key hormonal balances and histopathology of the endangered Caspian brown trout (Salmo trutta caspius).

PubMed

Shirdel, Iman; Kalbassi, Mohammad Reza

2016-01-01

Endocrine disruptor chemicals (EDCs) potentially pose a hazard to endangered species. Evaluation of the sensitivity of these species to EDCs could be helpful for protecting their populations. So, the present study investigated the adverse effects of nonylphenol, an EDC, on the endocrine hormones and histopathology of male and female juvenile Caspian brown trout (Salmo trutta caspius) following 21 days of exposure to nominal concentrations of 1, 10 and 100 μg/l. The results showed that the HSI and plasma total calcium of male and female fishes exposed to 100 μg/l nonylphenol were significantly increased compared with the control groups (P<0.001). The male plasma T3 level was significantly decreased in 10 (P<0.01) and 100 (P<0.001) μg/l nonylphenol. The female T3 level increased in 1 μg/l nonylphenol concentration (P<0.05). The plasma T4 of males showed significant elevation in fishes exposed to 100 μg/l nonylphenol (P<0.05), but no change for females in any of treatment groups relative to controls (P>0.05). No significant effect of nonylphenol exposure was observed on male plasma TSH levels (P>0.05), whereas, in females, nonylphenol at all concentrations significantly reduced TSH levels. A bell-shaped response was observed in male and female plasma GH levels. Moreover, various histopathological lesions were observed in gill and intestine tissues of fishes exposed to different nonylphenol concentrations. These results demonstrate the high sensitivity of this endangered species to even environmentally relevant concentrations of nonylphenol. Furthermore, Caspian brown trout could be used as bioindicators reflecting the toxicity of nonylphenol. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel technique of Roux-en-Y gastric bypass reversal for postprandial hyperinsulinemic hypoglycaemia: A case report.

PubMed

Qvigstad, E; Gulseth, H L; Risstad, H; le Roux, C W; Berg, T J; Mala, T; Kristinsson, J A

2016-01-01

We describe an evaluation of the effects of partial Roux-en-Y gastric bypass (RYGB) reversal on postprandial hyperinsulinaemic hypoglycaemia, insulin and GLP-1 levels. A 37 year old man was admitted with neuroglycopenia (plasma-glucose 1.6mmol/l) 18 months after RYGB, with normal 72h fasting test and abdominal CT. Despite dietary modifications and medical treatment, the hypoglycaemic episodes escalated in frequency. Feeding by a gastrostomy tube positioned in the gastric remnant did not prevent severe episodes of hypoglycaemia. A modified reversal of the RYGB was performed. Mixed meal tests were done perorally (PO), through the gastrostomy tube 1 (GT1), 4 weeks (GT2) after placement and 4 weeks after reversal (POr), with assessment of glucose, insulin and GLP-1 levels. Plasma-glucose increased to a maximum of 9.6, 5.4, 6.5 and 5.8mmol/l at the PO, GT1, GT2 and POr tests respectively. The corresponding insulin levels were 2939, 731, 725 and 463pmol/l. A decrease of plasma-glucose followed: 2.2, 3.0, 3.9 and 2.9mmol/l respectively and insulin levels were suppressed at 150min: 45, 22, 21 and 14pmol/l, respectively. GLP-1 levels increased in the PO test (60min: 122pmol/l, 21 fold of basal), but was attenuated in the two latter tests (12-23pmol/l at 60min). Reduction of plasma-glucose, insulin and GLP-1 excursions and symptoms were seen after gastric tube placement and partial RYGB reversal. This attenuation of GLP-1 response to feeding could reflect an adaptation to nutrients. Copyright © 2016. Published by Elsevier Ltd.

Controlling the misuse of cobalt in horses.

PubMed

Ho, Emmie N M; Chan, George H M; Wan, Terence S M; Curl, Peter; Riggs, Christopher M; Hurley, Michael J; Sykes, David

2015-01-01

Cobalt is a well-established inducer of hypoxia-like responses, which can cause gene modulation at the hypoxia inducible factor pathway to induce erythropoietin transcription. Cobalt salts are orally active, inexpensive, and easily accessible. It is an attractive blood doping agent for enhancing aerobic performance. Indeed, recent intelligence and investigations have confirmed cobalt was being abused in equine sports. In this paper, population surveys of total cobalt in raceday samples were conducted using inductively coupled plasma mass spectrometry (ICP-MS). Urinary threshold of 75 ng/mL and plasma threshold of 2 ng/mL could be proposed for the control of cobalt misuse in raceday or in-competition samples. Results from administration trials with cobalt-containing supplements showed that common supplements could elevate urinary and plasma cobalt levels above the proposed thresholds within 24 h of administration. It would therefore be necessary to ban the use of cobalt-containing supplements on raceday as well as on the day before racing in order to implement and enforce the proposed thresholds. Since the abuse with huge quantities of cobalt salts can be done during training while the use of legitimate cobalt-containing supplements are also allowed, different urinary and plasma cobalt thresholds would be required to control cobalt abuse in non-raceday or out-of-competition samples. This could be achieved by setting the thresholds above the maximum urinary and plasma cobalt concentrations observed or anticipated from the normal use of legitimate cobalt-containing supplements. Urinary threshold of 2000 ng/mL and plasma threshold of 10 ng/mL were thus proposed for the control of cobalt abuse in non-raceday or out-of-competition samples. Copyright © 2014 John Wiley & Sons, Ltd.

The effect of long-term corticosterone treatment on blood cell differentials and function in laboratory and wild-caught amphibian models.

PubMed

Falso, Paul G; Noble, Christopher A; Diaz, Jesus M; Hayes, Tyrone B

2015-02-01

The effect of long-term stress on amphibian immunity is not well understood. We modeled a long-term endocrine stress scenario by elevating plasma corticosterone in two species of amphibians and examined effects on white blood cell differentials and innate immune activity. Plasma corticosterone was elevated in American bullfrogs (Lithobates catesbeianus) by surgically implanting corticosterone capsules and in African clawed frogs (Xenopus laevis) by immersion in corticosterone-treated water. To provide a context for our results within endogenous corticosterone fluctuations, diurnal plasma corticosterone cycles were determined. A daily low of corticosterone was observed in X. laevis at 12:00, while a significant pattern was not observed in L. catesbeianus. Elevated plasma corticosterone levels increased the ratio of peripheral neutrophils to lymphocytes, in both species, and decreased eosinophil concentrations in L. catesbeianus over a long-term period. Whole blood oxidative burst generally correlated with neutrophil concentrations, and thus was increased with corticosterone treatment, significantly in L. catesbeianus. In L. catesbeianus, an endogenous response of eosinophils and lymphocytes to implanted empty (sham) capsules was observed, but this effect was attenuated by corticosterone. Peripheral monocyte and basophil concentrations were not significantly altered by corticosterone treatment in either species. Our results show that long-term stress can alter amphibian immune parameters for extended periods and may play a role in susceptibility to disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of L-arginine supplementation on immune responsiveness in patients with sickle cell disease.

PubMed

Scavella, Arnette; Leiva, Lily; Monjure, Hanh; Zea, Arnold H; Gardner, Renee V

2010-08-01

L-arginine (L-Arg) is deficient in sickle cell disease (SSD) during vasoocclusion. We investigated possible causal relationship between L-Arg deficiency and immune dysfunction in SSD in steady-state. Fifteen patients with SSD in steady-state and 13 controls were studied. Plasma L-Arg levels were measured using liquid chromatography. T cell subsets and CD3zeta (CD3zeta) chain expression were analyzed using flow cytometry. Lymphocyte proliferative response to phytohemagglutinin (PHA) and production of IL-6 and interferon-gamma (IFN-gamma) were evaluated with and without L-Arg. SSD patients had significantly lower L-Arg levels than controls. CD3 and CD19 cell populations were comparable for both groups, but SSD patients had above normal numbers of natural killer cells (P = 0.06). Patients and controls exhibited significantly increased lymphocyte blastogenesis to PHA after introduction of L-Arg to cultures; response of patients was significantly greater than values for control individuals. Proliferative response to candida in SSD patients was significantly lower than in controls; L-Arg supplementation did not increase this response. L-Arg had no effect on blastogenic response to PPD and candida albicans. No effect was likewise seen in production of IL-6 and IFN-gamma after addition of L-Arg. CD3zeta chain expression increased after addition of L-Arg in both groups; differences were insignificant. L-Arg levels in steady-state SSD are significantly lower than in controls. L-Arg supplementation enhanced lymphocyte blastogenesis to PHA for both controls and patients, but not in response to antigen. There were no significant differences in CD3zeta chain expression although upregulation of expression occurred after L-Arg supplementation for both groups. (c) 2010 Wiley-Liss, Inc.

77 FR 55201 - State Energy Advisory Board (STEAB); Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-07

.... L. 92- 463; 86 Stat.770) requires that public notice of these meetings be announced in the Federal... responsibilities as designated in the State Energy Efficiency Programs Improvement Act of 1990 (Pub. L. 101-440... partnerships, new initiatives and technologies being created at the Laboratory, explore possible technology...

Sarcoidosis mimicking toxoplasmosis with severe hypercalcaemia and normal 1,25-dihydroxy vitamin D.

PubMed

Levy, Y; Hayek, T; Finkelstein, R

1996-09-01

We report a case of a female patient with sarcoidosis who presented with a generalized lymphadenopathy and a strong IgG serological test of toxoplasmosis. Progressive lymphadenopathy with a rising plasma calcium (up to 15 mg dL-1) with a normal plasma 1,25-dihydroxy vitamin D concentration occurred later. Corticosteroid therapy resulted in prompt clinical and biochemical responses with normalization of plasma calcium and a significant reduction in 1,25-dihydroxy vitamin D concentration. This is an exceptional presentation of sarcoidosis with severe hypercalcaemia and normal vitamin D metabolites.

Amelioration de l'adhesion de revetements organiques deposes par plasma froid sur polymeres pour applications biomedicales

NASA Astrophysics Data System (ADS)

Sbai, Marouan

Plasma surface modification is commonly used in biomedical field, for example to enhance cell adhesion and growth surrounding the stent covers without affecting its bulk properties. Plasma polymer (PP) deposition used to create thin films rich in functional groups, e.g. primary amines, known to enhance the cellular response and allow grafting of biomolecules especially on stent grafts. Thin film adhesion to stent polymeric cover should be considered especially as they will evolve in a biological environment. The aim of this project is to evaluate the adhesion of PP on polytetrafluoroethylene (PTFE) and polyethyleneterephthalate (PET). Thereafter, an ammonia plasma treatment on PTFE is performed prior to deposition of PP to optimize the PP/PTFE adhesion. PP studied here (referred to as "LP") is prepared from a mixture of ethylene (C2H4) and ammonia (NH3). It is deposited on two supports, PET and PTFE. The interfacial adhesion between the LP coating and the substrate was evaluated by "Peel-test 180 °" according to ASTM F1842. Staining of the surface after peel test followed by an image analysis was performed to determine the percentage of removed coating. Adhesion optimization is done by varying operating plasma parameters such as power, pressure and pretreatment time. Chemical analyses and wettability of LP and pretreated surfaces in dry and wet conditions are characterized by XPS and contact angle measurements, respectively. The adhesion of LP/PET was excellent in a dry environment (<1%), but lower under wet conditions (4+/-6% and 44+/-7% as minimum and maximum values at 5min and 60min of immersion in deionized water, respectively). However, 56% to 75% of the LP is removed from virgin PTFE in a dry and wet environment, respectively; percentages can be substantially reduced by plasma pretreatment (0% and 8+/-3% in air and 30min in deionized water). Almost no delamination was observed with NH3 plasma pretreatment at 15s, 100 mTorr and 50W. N2 plasma pretreatment, for comparison, proves much less effective. The LP/PTFE adhesion is considerably improved by plasma pretreatment compared to untreated samples. The chemical LP composition and the cell growth on LP/pretreated PTFE are not significantly affected by this pretreatment. Further investigations are required to explain the LP/PET low adhesion in wet conditions.

Ion mobility spectrometry as a simple and rapid method to measure the plasma propofol concentrations for intravenous anaesthesia monitoring

NASA Astrophysics Data System (ADS)

Wang, Xin; Zhou, Qinghua; Jiang, Dandan; Gong, Yulei; Li, Enyou; Li, Haiyang

2016-11-01

The plasma propofol concentration is important information for anaesthetists to monitor and adjust the anaesthesia depth for patients during a surgery operation. In this paper, a stand-alone ion mobility spectrometer (IMS) was constructed for the rapid measurement of the plasma propofol concentrations. Without any sample pre-treatment, the plasma samples were dropped on a piece of glass microfiber paper and then introduced into the IMS cell by the thermal desorption directly. Each individual measurement could be accomplished within 1 min. For the plasma propofol concentrations from 1 to 12 μg mL-1, the IMS response was linear with a correlation coefficient R2 of 0.998, while the limit of detection was evaluated to be 0.1 μg mL-1. These measurement results did meet the clinical application requirements. Furthermore, other clinically-often-used drugs, including remifentanil, flurbiprofen and atracurium, were found no significant interference with the qualitative and quantitative analysis of the plasma propofol. The plasma propofol concentrations measured by IMS were correlated well with those measured by the high performance liquid chromatography (HPLC). The results confirmed an excellent agreement between these two methods. Finally, this method was applied to monitor the plasma propofol concentrations for a patient undergoing surgery, demonstrating its capability of anaesthesia monitoring in real clinical environments.

Bioactivity of food peptides: biological response of rats to bovine milk whey peptides following acute exercise

PubMed Central

Moura, Carolina Soares; Lollo, Pablo Christiano Barboza; Morato, Priscila Neder; Risso, Eder Muller; Amaya-Farfan, Jaime

2017-01-01

ABSTRACT Background: Several physiologically beneficial effects of consuming a whey protein hydrolysate (WPH) have been attributed to the greater availability of bioactive peptides. Aims: The aim was to investigate the effect of four branched-chain amino acid- (BCAA-)containing dipeptides, present in WPH, on immune modulation, stimulation of HSP expression, muscle protein synthesis, glycogen content, satiety signals and the impact of these peptides on the plasma free amino acid profiles. Methods: The animals were divided in groups: control (rest, without gavage), vehicle (water), L-isoleucyl-L-leucine (lle-Leu), L-leucyl-L-isoleucine (Leu-lle), L-valyl-Lleucine (Val-Leu), L-leucyl-L-valine (Leu-Val) and WPH. All animals were submitted to acute exercise, except for control. Results: lle-Leu stimulated immune response, hepatic and muscle glycogen and HSP60 expression, whereas Leu-Val enhanced HSP90 expression. All dipeptides reduced glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, no changes were observed on leptin. All peptides inhibited NF-kB expression. The plasma amino acid time-course showed peptide-specific and isomer-specific metabolic features, including increases of the BCAAs. Conclusion: The data indicate that lle-Leu was effective to attenuate immune-suppression exercise-induced, promoted glycogen content and stimulated anti-stress effect (HSP). Furthermore, Leu-Val increased HSP90, p-4EBP1, p-mTOR and p-AMPK expression. The data suggest the involvement of these peptides in various beneficial functions of WPH consumption. PMID:28326005

Aspects of chemoattractant recognition by the alga Dunaliella tertiolecta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Millard, P.J.

Studies on the molecular nature of algal chemotaxis were performed using the halophilic chlorophyte Dunaliella tertiolecta as a model. Several physical and chemical parameters for generation of maximum chemotactic response in capillary assays are described. Inhibition of chemotaxis to NH/sub 4//sup +/ and several aromatic amino acid by sublethal concentrations of certain heavy metals, including Zn/sup 2 +/, Co/sup 2 +/, Ni/sup 2 +/, Cu/sup 2 +/, and Hg/sup 2 +/ is demonstrated. Inhibition by Zn/sup 2/ of the response of NH/sub 4//sup +/ is partially reversed by increased concentrations of Ca/sup 2 +/. Attraction of L-phenylalanine, L-tyrosine, L-tryptophan, theirmore » structural analogs, and other compounds has been quantified using a capillary assay. Radiolabeled L-phenylalanine was used as a ligand to investigate algal binding and uptake. No internalization of the amino acid by D. tertiolectra occurred, even after 3 hr. Specific binding of /sup 3/H-L-phenylalanine was below 100 molecules per alga at 10/sup -8/ M L-phenylalanine. No evidence for the alteration of L-phenylalnine by D. tertiolecta was found following 22 hr incubation with the substrate in light or darkness. To further probe the molecular components of the chemosensory system of D. tertiolecta, a procedure for isolation and purification of trinitrobenzene sulfonic acid (TNBS)-labeled plasma membrane vesicles was developed. Plasma membrane purity was assessed by criteria of chlorophyll content, succinic dehydrogenase activity and protein pattern.« less

Hematology and plasma chemistry reference intervals for cultured tilapia (Oreochromis hybrid).

PubMed

Hrubec, Terry C.; Cardinale, Jenifer L.; Smith, Stephen A.

2000-01-01

Tilapia are a commonly aquacultured fish yet little is known about their normal physiology and response to disease. In this study we determined the results of complete hematologic (n=40) and plasma biochemical profiles (n=63) in production tilapia (Oreochromis hybrids). The fish were raised in recirculating systems with a high stocking density (120 g/L), and were in the middle of a 15-month production cycle. Blood was analyzed using standard techniques, and reference intervals were determined using nonparametric methods. Non-production tilapia (n=15) from low-density tanks (4 g/L) also were sampled; the clinical chemistry results were compared to reference intervals from the fish raised in high-density tanks. Differences were noted in plasma protein, calcium and phosphorus concentrations, such that reference intervals for high-density production tilapia were not applicable to fish raised under different environmental and management conditions.

Increased plasma pancreatic polypeptide in chronic alcohol abuse.

PubMed

Fink, R S; Adrian, T E; Margot, D H; Bloom, S R

1983-04-01

Post-prandial plasma gastrointestinal hormone profiles were measured in nine chronic alcoholics, one and fourteen days after complete alcohol withdrawal. Basal plasma pancreatic polypeptide concentration (PP--mean +/- SE mean) was significantly greater in alcoholics (control, 28 +/- 5 pmol/l; alcoholics, post-withdrawal day 1, 62 +/- 14 pmol/l, P less than 0.05; and post-withdrawal day 14, 89 +/- 17 pmol/1, P less than 0.005). The total integrated (TIR) PP response following a test breakfast was similarly elevated (control, 442 +/- 63 units; alcoholics, day 1, 1310 +/- 231 units, P less than 0.005; day 14,1066 +/- 66, P less than 0.005). Basal and TIR values for gastrin, gastric inhibitory peptide, insulin and glucagon were similar in alcoholics and controls. As PP has been shown to inhibit pancreatic exocrine enzyme secretion, these findings may help explain the abnormal pancreatic function seen frequently in alcoholics.

Effect of dosage and application mode of L-carnitine on plasma lipid and egg-yolk cholesterol of turkeys, hatchability of eggs and post-hatch growth of their offsprings.

PubMed

Oso, A O; Fafiolu, A O; Adeleke, M A; Ladokun, O A; Sobayo, R A; Jegede, A V; Peters, S O; Oyebamiji, O A; Akinsola, J

2014-08-01

The effect of dosage and application mode of L-carnitine on plasma lipid and egg-yolk cholesterol of breeder turkeys, hatchability of eggs and post-hatch growth response was investigated using 180 breeder hens. The hens were assigned to six dietary treatments in a 2 × 3 factorial arrangements of two application modes of L-carnitine (diet and drinking water) supplemented at 0, 50 and 100 ppm (mg/kg or mg/l) levels, respectively. Each treatment was replicated five times with six hens per replicate. Dietary inclusion of 50 ppm L-carnitine showed the lowest (p < 0.01) plasma total cholesterol (TC) and low-density lipoprotein concentration (LDL). Breeder hens offered 50 ppm L-carnitine with no regard to application mode recorded the highest (p < 0.01) plasma high-density lipoprotein (HDL). Hens offered 50 and 100 ppm L-carnitine irrespective of application mode also showed reduced (p < 0.01) egg-yolk TC concentration at 32 weeks of age. Dietary supplementation of 50 ppm L-carnitine for breeder turkeys recorded the lowest (p < 0.01) egg-yolk triglyceride (TG) at 40 weeks of age. Hens offered 50 ppm L-carnitine irrespective of application mode recorded the highest (p < 0.05) hen-day egg production. Incidence of dead-in-shell also reduced (p < 0.05) with increasing dosage of L-carnitine. Dietary supplementation of 50 ppm and oral application in drinking water of 100 ppm L-carnitine for breeder turkeys resulted in highest (p < 0.05) egg fertility. Offsprings from breeder hens fed diets supplemented with L-carnitine recorded no post-hatch mortality. Highest (p < 0.05) post-hatch final live weight and weight gain was obtained with poults obtained from hens fed diet supplemented with 50 ppm L-carnitine. In conclusion, dietary supplementation of 50 ppm L-carnitine for turkey hens showed improved serum lipid profile, egg fertility, reduced dead-in-shell, egg-yolk cholesterol and resulted in improved post-hatch growth performance.

Recent progress towards a physics-based understanding of the H-mode transition

DOE PAGES

Tynan, G. R.; Cziegler, I.; Diamond, P. H.; ...

2016-01-22

Results from recent experiment and numerical simulation point towards a picture of the L-H transition in which edge shear flows interacting with edge turbulence create the conditions needed to produce a non-zero turbulent Reynolds stress at and just inside the LCFS during L-mode discharges. This stress acts to reinforce the shear flow at this location and the flow drive gets stronger as heating is increased. The L-H transition ensues when the rate of work done by this stress is strong enough to drive the shear flow to large values, which then grows at the expense of the turbulence intensity. Themore » drop in turbulence intensity momentarily reduces the heat flux across the magnetic flux surface, which then allows the edge plasma pressure gradient to build. A sufficiently strong ion pressure gradient then locks in the H-mode state. The results are in general agreement with previously published reduced 0D and 1D predator prey models. An extended predator–prey model including separate ion and electron heat channels yields a non-monotonic power threshold dependence on plasma density provided that the fraction of heat deposited on the ions increases with plasma density. Possible mechanisms to explain other macroscopic transition threshold criteria are identified. A number of open questions and unexplained observations are identified, and must be addressed and resolved in order to build a physics-based model that can yield predictions of the macroscopic conditions needed for accessing H-mode.« less

Studies of a plasma with a hot dense core in LAPD

NASA Astrophysics Data System (ADS)

van Compernolle, Bart; Gekelman, Walter; Pribyl, Patrick; Cooper, Chris

2009-11-01

Recently, considerable effort in the LArge Plasma Device at UCLA (LAPD) has gone into the study of large cathodes which would enable higher discharge currents and higher densities. The new cathode is made out of Lanthanum HexaBoride (LaB6). LaB6 has a low work function and has higher emissivity than Barium oxide coated cathodes. The operating temperature of LaB6 cathodes lies above 1600 degrees Celsius. Tests of this cathode in the Enormous Toroidal Plasma Device (ETPD) showed that densities in excess of 2 10^13 cm-3 and electron temperatures of 12 eV are feasible. Small LaB6 cathodes (3mm - 2cm) have been used before in LAPD in several experiments on heat transport and on magnetized flux ropes. The cathode presented in this paper has a 8 cm diameter, and can be positioned at different radial locations. The cathode will be pulsed into the standard background plasma (ne= 2 10^12 cm-3, .25 <=Te<=6 eV, dia = 60 cm, L = 18 m) creating a plasma with a hot dense core. We present the characterization of the core plasma at different conditions. Studies of the heat transport and density spreading at the interface between the core plasma and background plasma will be done by use of a variety of probes (Langmuir, magnetic, Mach, emissive) as well as fast photography.

Secondary electron emission from plasma-generated nanostructured tungsten fuzz

DOE PAGES

Patino, M.; Raitses, Y.; Wirz, R.

2016-11-14

Recently, several researchers (e.g., Q. Yang, Y.-W. You, L. Liu, H. Fan, W. Ni, D. Liu, C. S. Liu, G. Benstetter, and Y. Wang, Scientific Reports 5, 10959 (2015)) have shown that tungsten fuzz can grow on a hot tungsten surface under bombardment by energetic helium ions in different plasma discharges and applications, including magnetic fusion devices with plasma facing tungsten components. This work reports direct measurements of the total effective secondary electron emission (SEE) from tungsten fuzz. Using dedicated material surface diagnostics and in-situ characterization, we find two important results: (1) SEE values for tungsten fuzz are 40-63% lowermore » than for smooth tungsten and (2) the SEE values for tungsten fuzz are independent of the angle of the incident electron. The reduction in SEE from tungsten fuzz is most pronounced at high incident angles, which has important implications for many plasma devices since in a negative-going sheath the potential structure leads to relatively high incident angles for the electrons at the plasma confining walls. Overall, low SEE will create a relatively higher sheath potential difference that reduces plasma electron energy loss to the confining wall. Thus the presence or self-generation in a plasma of a low SEE surface such as tungsten fuzz can be desirable for improved performance of many plasma devices.:7px« less

Uric acid but not apple polyphenols is responsible for the rise of plasma antioxidant activity after apple juice consumption in healthy subjects.

PubMed

Godycki-Cwirko, Maciek; Krol, Maciej; Krol, Bogusław; Zwolinska, Anna; Kolodziejczyk, Krzysztof; Kasielski, Marek; Padula, Gianluca; Grebowski, Jacek; Grębocki, Jacek; Kazmierska, Paulina; Kazimierska, Paulina; Miatkowski, Marcin; Markowski, Jarosław; Nowak, Dariusz

2010-08-01

To determine whether (1) rapid consumption of 1 L of apple juice increases blood antioxidant capacity, measured as ferric-reducing ability of plasma (FRAP) and serum 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, and (2) apple polyphenols or fructose-induced elevation of plasma uric acid contributes to post-juice increase of blood antioxidant activity. The study involved 12 (mean age 32 ± 5 years, mean body weight 73 ± 7 kg) healthy nonsmoking subjects. Tested subjects consumed 1 L of clear apple juice and then FRAP; serum DPPH-scavenging activity, serum uric acid, and total plasma phenolics and quercetin levels were measured just before juice ingestion and 1, 2.5, and 4 hours after ingestion. This was repeated 3 times with 4-day intervals, but volunteers drank either 1 L of clear apple juice without polyphenols (placebo), or 1 L of cloudy apple juice (positive control), or 1 L of water (negative control) at the time. All juices had similar content of sugars (i.e., saccharose, glucose, and fructose) and precisely defined composition of phenolics and antioxidant activity. Consumption of all 3 juices transiently increased FRAP and serum DPPH-scavenging activity, with peak values at 1 hour post-juice ingestion. This was paralleled by the rise of serum uric acid, but no significant changes in plasma total phenolics and quercetin levels were observed after all dietary interventions. At the same time, no substantial differences were found between juices (especially between clear apple juice and clear apple juice without polyphenols) concerning the measured variables. A strong significant correlation was noted instead between serum uric acid and plasma antioxidant activity at all analyzed time points, before and after juice ingestion. Plasma total phenolics and quercetin levels were not associated with FRAP and serum DPPH radical-scavenging activity. We have demonstrated that rapid consumption of apple juice increased plasma antioxidant activity in healthy subjects; this was caused by the fructose-induced rise of serum uric acid levels, but was not due to the presence of antioxidant polyphenols in juice. Thus, short-term consumption of apple juice seems not to be the effective dietary intervention to augment plasma antioxidant activity due to the concomitant possibility for uric acid to be a risk factor for several diseases, as verified by other authors.

Low Temperature Plasma Medicine

NASA Astrophysics Data System (ADS)

Graves, David

2013-10-01

Ionized gas plasmas near room temperature are used in a remarkable number of technological applications mainly because they are extraordinarily efficient at exploiting electrical power for useful chemical and material transformations near room temperature. In this tutorial address, I will focus on the newest area of low temperature ionized gas plasmas (LTP), in this case operating under atmospheric pressure conditions, in which the temperature-sensitive material is living tissue. LTP research directed towards biomedical applications such as sterilization, surgery, wound healing and anti-cancer therapy has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that LTP readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. I will review the evidence suggesting that RONS generated by plasmas are responsible for their observed therapeutic effects. Other possible bio-active mechanisms include electric fields, charges and photons. It is common in LTP applications that synergies between different mechanisms can play a role and I will review the evidence for synergies in plasma biomedicine. Finally, I will address the challenges and opportunities for plasma physicists to enter this novel, multidisciplinary field.

Explosively Generated Plasmas: Measurement and Models of Shock Generation and Material Interactions

NASA Astrophysics Data System (ADS)

Emery, Samuel; Elert, Mark; Giannuzzi, Paul; Le, Ryan; McCarthy, Daniel; Schweigert, Igor

2017-06-01

Explosively generated plasmas (EGPs) are created by the focusing of a shock produced from an explosive driver via a conical waveguide. In the waveguide, the gases from the explosive along with the trapped air are accelerated and compressed (via Mach stemming) to such extent that plasma is produced. These EGPs have been measured in controlled experiments to achieve temperatures on the order of 1 eV and velocities as high as 25 km/s. We have conducted a combined modeling and measurement effort to increase the understanding for design purposes of the shock generation of EGPs and the interaction of EGP with explosive materials. Such efforts have led to improved measures of pressure and temperature, spatial structure of the plasma, and the decomposition/deflagration behavior of RDX upon exposure to an EGP. Funding provided by the Environmental Security Technology Certification Program (ESTCP) Munitions Response program area.

Laboratory evidence of dynamo amplification of magnetic fields in a turbulent plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tzeferacos, P.; Rigby, A.; Bott, A. F. A.

Magnetic fields are ubiquitous in the Universe. The energy density of these fields is typically comparable to the energy density of the fluid motions of the plasma in which they are embedded, making magnetic fields essential players in the dynamics of the luminous matter. The standard theoretical model for the origin of these strong magnetic fields is through the amplification of tiny seed fields via turbulent dynamo to the level consistent with current observations. However, experimental demonstration of the turbulent dynamo mechanism has remained elusive, since it requires plasma conditions that are extremely hard to re-create in terrestrial laboratories. Heremore » in this paper, we demonstrate, using laser-produced colliding plasma flows, that turbulence is indeed capable of rapidly amplifying seed fields to near equipartition with the turbulent fluid motions. These results support the notion that turbulent dynamo is a viable mechanism responsible for the observed present-day magnetization.« less

Laboratory evidence of dynamo amplification of magnetic fields in a turbulent plasma

DOE PAGES

Tzeferacos, P.; Rigby, A.; Bott, A. F. A.; ...

2018-02-09

Magnetic fields are ubiquitous in the Universe. The energy density of these fields is typically comparable to the energy density of the fluid motions of the plasma in which they are embedded, making magnetic fields essential players in the dynamics of the luminous matter. The standard theoretical model for the origin of these strong magnetic fields is through the amplification of tiny seed fields via turbulent dynamo to the level consistent with current observations. However, experimental demonstration of the turbulent dynamo mechanism has remained elusive, since it requires plasma conditions that are extremely hard to re-create in terrestrial laboratories. Heremore » in this paper, we demonstrate, using laser-produced colliding plasma flows, that turbulence is indeed capable of rapidly amplifying seed fields to near equipartition with the turbulent fluid motions. These results support the notion that turbulent dynamo is a viable mechanism responsible for the observed present-day magnetization.« less

Laboratory evidence of dynamo amplification of magnetic fields in a turbulent plasma.

PubMed

Tzeferacos, P; Rigby, A; Bott, A F A; Bell, A R; Bingham, R; Casner, A; Cattaneo, F; Churazov, E M; Emig, J; Fiuza, F; Forest, C B; Foster, J; Graziani, C; Katz, J; Koenig, M; Li, C-K; Meinecke, J; Petrasso, R; Park, H-S; Remington, B A; Ross, J S; Ryu, D; Ryutov, D; White, T G; Reville, B; Miniati, F; Schekochihin, A A; Lamb, D Q; Froula, D H; Gregori, G

2018-02-09

Magnetic fields are ubiquitous in the Universe. The energy density of these fields is typically comparable to the energy density of the fluid motions of the plasma in which they are embedded, making magnetic fields essential players in the dynamics of the luminous matter. The standard theoretical model for the origin of these strong magnetic fields is through the amplification of tiny seed fields via turbulent dynamo to the level consistent with current observations. However, experimental demonstration of the turbulent dynamo mechanism has remained elusive, since it requires plasma conditions that are extremely hard to re-create in terrestrial laboratories. Here we demonstrate, using laser-produced colliding plasma flows, that turbulence is indeed capable of rapidly amplifying seed fields to near equipartition with the turbulent fluid motions. These results support the notion that turbulent dynamo is a viable mechanism responsible for the observed present-day magnetization.

Simultaneous determination of albumin and low-molecular-mass thiols in plasma by HPLC with UV detection.

PubMed

Borowczyk, Kamila; Wyszczelska-Rokiel, Monika; Kubalczyk, Paweł; Głowacki, Rafał

2015-02-15

In this paper, we describe a simple and robust HPLC based method for determination of total low- and high-molecular-mass thiols, protein S-linked thiols and reduced albumin in plasma. The method is based on derivatization of analytes with 2-chloro-1-methylquinolinium tetrafluoroborate, separation and quantification by reversed-phase liquid chromatography followed by UV detection. Disulfides were converted to their thiol counterparts by reductive cleavage with tris(2-carboxyethyl)phosphine. Linearity in detector response for total thiols was observed over the range of 1-40 μmol L(-1) for Hcy and glutathione (GSH), 5-100 μmol L(-1) for Cys-Gly, 20-300 μmol L(-1) for Cys and 3.1-37.5 μmol L(-1) (0.2-2.4gL(-1)) for human serum albumin (HSA). For the protein S-bound forms these values were as follows: 0.5-30 μmol L(-1) for Hcy and GSH, 2.5-60 μmol L(-1) for Cys-Gly and 5-200 μmol L(-1) for Cys. The LOQs for total HSA, Cys, Hcy, Cys-Gly and GSH were 0.5, 0.2, 0.4, 0.3 and 0.4 μmol L(-1), respectively. The estimated validation parameters for all analytes are more than sufficient to allow the analytical method to be used for monitoring of the total and protein bound thiols as well as redox status of HSA in plasma. Copyright © 2015 Elsevier B.V. All rights reserved.

Validation of TGLF in C-Mod and DIII-D using machine learning and integrated modeling tools

NASA Astrophysics Data System (ADS)

Rodriguez-Fernandez, P.; White, Ae; Cao, Nm; Creely, Aj; Greenwald, Mj; Grierson, Ba; Howard, Nt; Meneghini, O.; Petty, Cc; Rice, Je; Sciortino, F.; Yuan, X.

2017-10-01

Predictive models for steady-state and perturbative transport are necessary to support burning plasma operations. A combination of machine learning algorithms and integrated modeling tools is used to validate TGLF in C-Mod and DIII-D. First, a new code suite, VITALS, is used to compare SAT1 and SAT0 models in C-Mod. VITALS exploits machine learning and optimization algorithms for the validation of transport codes. Unlike SAT0, the SAT1 saturation rule contains a model to capture cross-scale turbulence coupling. Results show that SAT1 agrees better with experiments, further confirming that multi-scale effects are needed to model heat transport in C-Mod L-modes. VITALS will next be used to analyze past data from DIII-D: L-mode ``Shortfall'' plasma and ECH swing experiments. A second code suite, PRIMA, allows for integrated modeling of the plasma response to Laser Blow-Off cold pulses. Preliminary results show that SAT1 qualitatively reproduces the propagation of cold pulses after LBO injections and SAT0 does not, indicating that cross-scale coupling effects play a role in the plasma response. PRIMA will be used to ``predict-first'' cold pulse experiments using the new LBO system at DIII-D, and analyze existing ECH heat pulse data. Work supported by DE-FC02-99ER54512, DE-FC02-04ER54698.

Usefulness of anti-rabphilin-3A antibodies for diagnosing central diabetes insipidus in the third trimester of pregnancy.

PubMed

Sakurai, Kanako; Yamashita, Rika; Niituma, Satsuki; Iwama, Shintaro; Sugimura, Yoshihisa; Arihara, Zenei; Takahashi, Kazuhiro

2017-06-29

We report a 27-year-old pregnant woman with polyuria, polydipsia and headache in the third trimester of pregnancy. Hypernatremia (153 mEq/L), high plasma osmolality (300 mOsm/kgH 2 O) and low urinary osmolality (92 mOsm/kgH 2 O) were observed at the admission to our hospital. Plasma arginine vasopressin (AVP) level was inappropriately low (2.2 pg/mL) compared to the high plasma osmolality. Plasma AVP responses to hypertonic-saline infusion were blunted, and her urine osmolality increased in response to desmopressin. The diagnosis of central diabetes insipidus was made from these results. Magnetic resonance imaging (MRI) of hypothalamic-pituitary region demonstrated a significant enlargement of the pituitary stalk, suggesting the presence of hypophysitis. In addition, serum anti-rabphilin-3A antibodies that have been recently reported as a biomarker of lymphocytic infundibulo-neurohypophysitis, were positive. Diabetes insipidus continued after delivery, suggesting that polyuria was not mainly due to excessive vasopressinase activity or reduced renal sensitivity to AVP by prostaglandin E 2 that can cause temporal polyuria during pregnancy. We therefore clinically diagnosed central diabetes insipidus due to lymphocytic infundibulo-neurohypophysitis, without performing invasive transsphenoidal pituitary biopsy. This case suggested the usefulness of anti-rabphilin-3A antibodies for the etiological diagnosis of central diabetes insipidus during pregnancy.

Pharmacokinetic-pharmacodynamic modelling of the antihistaminic (H1) effect of bilastine.

PubMed

Jauregizar, Nerea; de la Fuente, Leire; Lucero, Maria Luisa; Sologuren, Ander; Leal, Nerea; Rodríguez, Mónica

2009-01-01

To model the pharmacokinetic and pharmacodynamic relationship of bilastine, a new histamine H(1) receptor antagonist, from single- and multiple-dose studies in healthy adult subjects. The pharmacokinetic model was developed from different single-dose and multiple-dose studies. In the single-dose studies, a total of 183 subjects received oral doses of bilastine 2.5, 5, 10, 20, 50, 100, 120, 160, 200 and 220 mg. In the multiple-dose studies, 127 healthy subjects received bilastine 10, 20, 40, 50, 80, 100, 140 or 200 mg/day as multiple doses during a 4-, 7- or 14-day period. The pharmacokinetic profile of bilastine was investigated using a simultaneous analysis of all concentration-time data by means of nonlinear mixed-effects modelling population pharmacokinetic software NONMEM version 6.1. Plasma concentrations were modelled according to a two-compartment open model with first-order absorption and elimination. For the pharmacodynamic analysis, the inhibitory effect of bilastine (inhibition of histamine-induced wheal and flare) was assessed on a preselected time schedule, and the predicted typical pharmacokinetic profile (based on the pharmacokinetic model previously developed) was used. An indirect response model was developed to describe the pharmacodynamic relationships between flare or wheal areas and bilastine plasma concentrations. Finally, once values of the concentration that produced 50% inhibition (IC(50)) had been estimated for wheal and flare effects, simulations were carried out to predict plasma concentrations for the doses of bilastine 5, 10 and 20 mg at steady state (72-96 hours). A non-compartmental analysis resulted in linear kinetics of bilastine in the dose range studied. Bilastine was characterized by two-compartmental kinetics with a rapid-absorption phase (first-order absorption rate constant = 1.50 h(-1)), plasma peak concentrations were observed at 1 hour following administration and the maximal response was observed at approximately 4 hours or later. Concerning the selected pharmacodynamic model to fit the data (type I indirect response model), this selection is attributable to the presence of inhibitory bilastine plasma concentrations that decrease the input response function, i.e. the production of the skin reaction. This model resulted in the best fit of wheal and flare data. The estimates (with relative standard errors expressed in percentages in parentheses) of the apparent zero-order rate constant for flare or wheal spontaneous appearance (k(in)), the first-order rate constant for flare or wheal disappearance (k(out)) and bilastine IC(50) values were 0.44 ng/mL/h (14.60%), 1.09 h(-1) (15.14%) and 5.15 ng/mL (16.16%), respectively, for wheal inhibition, and 11.10 ng/mL/h (8.48%), 1.03 h(-1) (8.35%) and 1.25 ng/mL (14.56%), respectively, for flare inhibition. The simulation results revealed that bilastine plasma concentrations do not remain over the IC(50) value throughout the inter-dose period for doses of 5 and 10 mg. However, with a dose of 20 mg of bilastine administered every 24 hours, plasma concentrations remained over the IC(50) value during the considered period for the flare effect, and up to 20 hours for the wheal effect. Pharmacokinetic and pharmacodynamic relationships of bilastine were reliably described with the use of an indirect response pharmacodynamic model; this led to an accurate prediction of the pharmacodynamic activity of bilastine.

Acid Gradient across Plasma Membrane Can Drive Phosphate Bond Synthesis in Cancer Cells: Acidic Tumor Milieu as a Potential Energy Source

PubMed Central

Dhar, Gautam; Sen, Suvajit; Chaudhuri, Gautam

2015-01-01

Aggressive cancers exhibit an efficient conversion of high amounts of glucose to lactate accompanied by acid secretion, a phenomenon popularly known as the Warburg effect. The acidic microenvironment and the alkaline cytosol create a proton-gradient (acid gradient) across the plasma membrane that represents proton-motive energy. Increasing experimental data from physiological relevant models suggest that acid gradient stimulates tumor proliferation, and can also support its energy needs. However, direct biochemical evidence linking extracellular acid gradient to generation of intracellular ATP are missing. In this work, we demonstrate that cancer cells can synthesize significant amounts of phosphate-bonds from phosphate in response to acid gradient across plasma membrane. The noted phenomenon exists in absence of glycolysis and mitochondrial ATP synthesis, and is unique to cancer. Biochemical assays using viable cancer cells, and purified plasma membrane vesicles utilizing radioactive phosphate, confirmed phosphate-bond synthesis from free phosphate (Pi), and also localization of this activity to the plasma membrane. In addition to ATP, predominant formation of pyrophosphate (PPi) from Pi was also observed when plasma membrane vesicles from cancer cells were subjected to trans-membrane acid gradient. Cancer cytosols were found capable of converting PPi to ATP, and also stimulate ATP synthesis from Pi from the vesicles. Acid gradient created through glucose metabolism by cancer cells, as observed in tumors, also proved critical for phosphate-bond synthesis. In brief, these observations reveal a role of acidic tumor milieu as a potential energy source and may offer a novel therapeutic target. PMID:25874623

Sustained response to standard dose osimertinib in a patient with plasma T790M-positive leptomeningeal metastases from primary lung adenocarcinoma.

PubMed

Chan, Oscar Siu-Hong; Leung, Warren Kam-Wing; Yeung, Rebecca Mei-Wan

2017-12-01

A 44-year-old male, never smoker, suffers from stage IV adenocarcinoma of the right lung with epidermal growth factor receptor (EGFR) exon-21 L858R point mutation on initial presentation. After 23 months of treatment with gefitinib, intercalated with multiple courses of radiotherapy, leptomeningeal metastases (LMs) developed. Acquired T790M mutation was confirmed by the droplet digital polymerase chain reaction plasma EGFR test. After switching to osimertinib at the standard dose, his neurocognitive function improved clinically, coupled with sustained radiological improvement. As this clinical entity is underrepresented in clinical trials, the practicability of plasma EGFR testing and the optimal dose-response relationship of osimertinib in T790M-positive lung cancer complicated with LM deserves further exploration. © 2017 John Wiley & Sons Australia, Ltd.

Cytokine Responses to Acute Exercise in Healthy Older Adults: The Effect of Cardiorespiratory Fitness

PubMed Central

Windsor, Mark T.; Bailey, Tom G.; Perissiou, Maria; Meital, Lara; Golledge, Jonathan; Russell, Fraser D.; Askew, Christopher D.

2018-01-01

Markers of chronic inflammation increase with aging, and are associated with cardiovascular disease prevalence and mortality. Increases in fitness with exercise training have been associated with lower circulating concentrations of cytokines known to have pro-inflammatory actions (such as interleukin-6 [IL-6]) and higher circulating concentrations of anti-inflammatory cytokines (interleukin-10 [IL-10]). However, the effect of cardiorespiratory fitness on acute cytokine responses to a single bout of exercise in healthy older individuals is unknown. We compared the response of plasma cytokines IL-6, tumor necrosis factor-alpha (TNF-α) and IL-10 to a bout of moderate-intensity continuous and higher-intensity interval exercise between older individuals with higher and lower levels of cardiorespiratory fitness. Sixteen lower-fit (VO2peak: 22.6±2.8 mL.kg−1.min−1) and fourteen higher-fit participants (VO2peak: 37.4±5.9 mL.kg−1.min−1) completed three 24 min experimental protocols in a randomized order: (1) moderate-intensity continuous exercise (40% of peak power output [PPO]); (2) higher-intensity interval exercise (12 × 1 min intervals at 70% PPO separated by 1 min periods at 10% PPO); or (3) non-exercise control. Plasma cytokines were measured at rest, immediately after, and during 90 min of recovery following exercise or control. Plasma IL-6 concentrations at baseline were greater in the higher-fit compared to the lower-fit group (P = 0.02), with no difference in plasma IL-10 or TNF-α concentrations at baseline between groups. Plasma IL-6 and IL-10 concentrations in both groups increased immediately after all protocols (IL-6: P = 0.02, IL-10: P < 0.01). However, there was no difference in the IL-6 and IL-10 response between the exercise and non-exercise (control) protocols. After all protocols, no changes in plasma TNF-α concentrations were observed in either the higher- or lower-fit groups. In this study, basal concentrations of circulating IL-6 were elevated in older individuals with higher levels of cardiorespiratory fitness. However, changes in plasma cytokine concentrations after exercise were not different to changes after non-exercise control in both the lower- and higher-fit groups. PMID:29599722

Population Pharmacokinetic-Pharmacodynamic Model of Oral Fludrocortisone and Intravenous Hydrocortisone in Healthy Volunteers.

PubMed

Hamitouche, Noureddine; Comets, Emmanuelle; Ribot, Mégane; Alvarez, Jean-Claude; Bellissant, Eric; Laviolle, Bruno

2017-05-01

This study aimed at describing the pharmacokinetics and the concentration-effect relationships of fludrocortisone and hydrocortisone on urinary sodium/potassium excretion in healthy volunteers. This was a placebo-controlled, randomized, double blind, crossover study, of oral fludrocortisone and intravenous hydrocortisone, given alone or in combination, in 12 healthy male volunteers. Nonlinear mixed-effects modeling was used to describe the pharmacokinetics and pharmacokinetic-pharmacodynamic relationships on urinary sodium/potassium ratio for each drug. A one-compartment model was used to describe fludrocortisone and hydrocortisone pharmacokinetics. Mean plasma half-life was 1.40 h (95%CI [0.80;2.10]) for fludrocortisone and 2.10 h (95%CI [1.78;2.40]) for hydrocortisone. Clearance was 40.8 L/h (95%CI [33.6;48]) for fludrocortisone and 30 L/h (95%CI [25.3;34.7]) for hydrocortisone. An indirect response model was used to describe effects on urinary sodium/potassium ratio. Fludrocortisone plasma concentrations showed a wider inter-individual dispersion than hydrocortisone plasma concentrations. Urinary sodium/potassium ratio variability was also higher with fludrocortisone as compared to hydrocortisone. The plasma concentration of drug producing 50% of maximal inhibition of urinary sodium/potassium (IC 50 ) was about 200 times lower for fludrocortisone (0.08 μg/L, 95%CI [0.035;0.125]) than for hydrocortisone (16.7 μg/L, 95%CI [10.5;22.9]). Simulations showed that a 4-time per day administration regimen allow to achieve steady fludrocortisone plasma concentrations with stable decrease in urinary sodium/potassium ratio after the second administration of fludrocortisone. Fludrocortisone and hydrocortisone have short and similar plasma elimination half-lives in healthy subjects. Fludrocortisone plasma concentrations and effect on urinary sodium/potassium ratio had a higher inter-individual variability as compared to hydrocortisone. The administration regimen of fludrocortisone should be reconsidered.

[Influence of age and gender on plasma norepinephrine changes produced by orthostatic stress].

PubMed

Arata de Bellabarba, G; Molina, C; Dávila Spinetti, D; Villarroel, V; Bellabarba, S A; Torres, A

2001-01-01

The aim of this work was to determine the effect of aging and gender on plasma norepinephrine (NE) response to orthostatic stress. Fifty-six men and sixty women non-smokers, sedentary, non-obese, were studied at supine and standing positions. On the basis of the age of the subjects, they were divided into three groups of either men or women. Group A, young, range 17-34 years, Group B, middle-age, range 40-60 years, and Group C: senescent, range 61-91 years. Senescent subjects had the highest absolute supine values of NE and significant differences between women and men were found in groups B Men: 298 +/- 15 pg/mL; Women: 348 +/- 14 pg/mL), and C (M: 386 +/- 29 pg/mL; W: 473 +/- 19 pg/mL), but not between young (M: 246 +/- 21 pg/mL; W: 261 +/- 18 pg/mL). NE increased markedly in response to the orthostatic stress but the relative (percentage) increases were smaller in the older subjects perhaps related to their elevated baseline levels. The highest percent positive variation was observed in group A (M: 85%; W: 82%). The oldest group (C), had the lowest variation (M: 23%; W: 21%). The relative increases in NE responses were not different in men and women. The orthostatic-induced variation in NE was negatively related to aging in both men and women (M: r = -0.654; p < 0.0001; W: r = -0.557; p < 0.0001). It is concluded that orthostatic stress induced rise of blood NE is attenuated by age but does not appear to be dependent on gender.

Arm and Intensity-Matched Leg Exercise Induce Similar Inflammatory Responses.

PubMed

Leicht, Christof A; Paulson, Thomas A W; Goosey-Tolfrey, Victoria L; Bishop, Nicolette C

2016-06-01

The amount of active muscle mass can influence the acute inflammatory response to exercise, associated with reduced risk for chronic disease. This may affect those restricted to upper body exercise, for example, due to injury or disability. The purpose of this study was to compare the inflammatory responses for arm exercise and intensity-matched leg exercise. Twelve male individuals performed three 45-min constant load exercise trials after determination of peak oxygen uptake for arm exercise (V˙O2peak A) and cycling (V˙O2peak C): 1) arm cranking exercise at 60% V˙O2peak A, 2) moderate cycling at 60% V˙O2peak C, and 3) easy cycling at 60% V˙O2peak A. Cytokine, adrenaline, and flow cytometric analysis of monocyte subsets were performed before and up to 4 h postexercise. Plasma IL-6 increased from resting concentrations in all trials; however, postexercise concentrations were higher for arm exercise (1.73 ± 1.04 pg·mL) and moderate cycling (1.73 ± 0.95 pg·mL) compared with easy cycling (0.87 ± 0.41 pg·mL; P < 0.04). Similarly, the plasma IL-1ra concentration in the recovery period was higher for arm exercise (325 ± 139 pg·mL) and moderate cycling (316 ± 128 pg·mL) when compared with easy cycling (245 ± 77 pg·mL, P < 0.04). Arm exercise and moderate cycling induced larger increases in monocyte numbers and larger increases of the classical monocyte subset in the recovery period than easy cycling (P < 0.05). The postexercise adrenaline concentration was lowest for easy cycling (P = 0.04). Arm exercise and cycling at the same relative exercise intensity induces a comparable acute inflammatory response; however, cycling at the same absolute oxygen uptake as arm exercise results in a blunted cytokine, monocyte, and adrenaline response. Relative exercise intensity appears to be more important to the acute inflammatory response than modality, which is of major relevance for populations restricted to upper body exercise.

Consequences of wave-particle interactions on chaotic acceleration

NASA Technical Reports Server (NTRS)

Schriver, David; Ashour-Abdalla, Maha

1991-01-01

The recent model of Ashour-Abdalla et al. (1991) has proposed that the earth's plasma sheet can be formed by chaotic acceleration in a magnetotail-like field configuration. The ion velocity distributions created by chaotic acceleration have unstable features and represent robust free energy sources for kinetic plasma waves that can modify the original distributions. In the plasma sheet boundary layer, field-aligned ion beamlets are formed which drive a host of instabilities creating a broadbanded noise spectrum and cause thermal spreading of the beamlets. In addition, there is strong heating of any cold background plasma that may be present. In the central plasma sheet, ion antiloss cone distributions are created which are unstable to very low frequency waves that saturate by filling the antiloss cone.

Guiding of laser pulses in plasma waveguides created by linearly-polarized femtosecond laser pulses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lemos, N.; Cardoso, L.; Geada, J.

We experimentally demonstrate that plasma waveguides produced with ultra-short laser pulses (sub-picosecond) in gas jets are capable of guiding high intensity laser pulses. This scheme has the unique ability of guiding a high-intensity laser pulse in a plasma waveguide created by the same laser system in the very simple and stable experimental setup. A hot plasma column was created by a femtosecond class laser that expands into an on-axis parabolic low density profile suitable to act as a waveguide for high intensity laser beams. We have successfully guided ~10 15 W cm -2 laser pulses in a 8 mm longmore » hydrogen plasma waveguide with a 35% guiding efficiency.« less

Guiding of laser pulses in plasma waveguides created by linearly-polarized femtosecond laser pulses

DOE PAGES

Lemos, N.; Cardoso, L.; Geada, J.; ...

2018-02-16

We experimentally demonstrate that plasma waveguides produced with ultra-short laser pulses (sub-picosecond) in gas jets are capable of guiding high intensity laser pulses. This scheme has the unique ability of guiding a high-intensity laser pulse in a plasma waveguide created by the same laser system in the very simple and stable experimental setup. A hot plasma column was created by a femtosecond class laser that expands into an on-axis parabolic low density profile suitable to act as a waveguide for high intensity laser beams. We have successfully guided ~10 15 W cm -2 laser pulses in a 8 mm longmore » hydrogen plasma waveguide with a 35% guiding efficiency.« less

CYP2B6*6 allele and age substantially reduce steady-state ketamine clearance in chronic pain patients: impact on adverse effects

PubMed Central

Li, Yibai; Jackson, Kate A; Slon, Barry; Hardy, Janet R; Franco, Michael; William, Leeroy; Poon, Peter; Coller, Janet K; Hutchinson, Mark R; Currow, David C; Somogyi, Andrew A

2015-01-01

Aims Ketamine analgesia is limited by low intrinsic efficacy compounded by large interindividual variability in drug responses, possibly due to the heterogeneity in drug concentration. The CYP2B6*6 allele is associated with substantially reduced ketamine metabolism in vitro and, therefore, may affect ketamine clearance. Our aims were to examine the impact of the CYP2B6*6 allele on ketamine plasma clearance and on adverse effects in chronic pain patients. Methods CYP2B6 genotypes were identified in 49 chronic pain patients who received 24 h continuous subcutaneous infusions of ketamine. Steady-state plasma concentrations of ketamine (Css,k) and norketamine (Css,nk) were determined using HPLC. Results The median plasma clearance of ketamine after 100 mg 24 h–1 dose was significantly lower in patients with the CYP2B6*6/*6 (21.6 l h–1) and CYP2B6*1/*6 (40.6 l h–1) genotypes compared with patients with the CYP2B6*1/*1 genotype (68.1 l h–1, P < 0.001). The ketamine : norketamine plasma metabolic ratio was significantly higher in patients with the CYP2B6*6/*6 genotype than in those with the CYP2B6*1/*6 and the CYP2B6*1/*1 genotypes (P < 0.001). Patients who experienced adverse effects had lower plasma clearance (45.6 l h-1) than those who did not (52.6 l h-1, P = 0.04). The CYP2B6*6 genotype and age, and their combined impact explained 40%, 30% and 60% of the variation in Css,k, respectively. Similar results were observed after higher doses. Conclusions The CYP2B6*6 allele is associated with a substantial decrease in steady-state ketamine plasma clearance in chronic pain patients. The decreased clearance and resultant higher plasma concentrations may be associated with a higher incidence of ketamine adverse effects. PMID:25702819

CYP2B6*6 allele and age substantially reduce steady-state ketamine clearance in chronic pain patients: impact on adverse effects.

PubMed

Li, Yibai; Jackson, Kate A; Slon, Barry; Hardy, Janet R; Franco, Michael; William, Leeroy; Poon, Peter; Coller, Janet K; Hutchinson, Mark R; Currow, David C; Somogyi, Andrew A

2015-08-01

Ketamine analgesia is limited by low intrinsic efficacy compounded by large interindividual variability in drug responses, possibly due to the heterogeneity in drug concentration. The CYP2B6*6 allele is associated with substantially reduced ketamine metabolism in vitro and, therefore, may affect ketamine clearance. Our aims were to examine the impact of the CYP2B6*6 allele on ketamine plasma clearance and on adverse effects in chronic pain patients. CYP2B6 genotypes were identified in 49 chronic pain patients who received 24 h continuous subcutaneous infusions of ketamine. Steady-state plasma concentrations of ketamine (Css,k ) and norketamine (Css,nk ) were determined using HPLC. The median plasma clearance of ketamine after 100 mg 24 h(-1) dose was significantly lower in patients with the CYP2B6*6/*6 (21.6 l h(-1) ) and CYP2B6*1/*6 (40.6 l h(-1) ) genotypes compared with patients with the CYP2B6*1/*1 genotype (68.1 l h(-1) , P < 0.001). The ketamine : norketamine plasma metabolic ratio was significantly higher in patients with the CYP2B6*6/*6 genotype than in those with the CYP2B6*1/*6 and the CYP2B6*1/*1 genotypes (P < 0.001). Patients who experienced adverse effects had lower plasma clearance (45.6 l h(-1) ) than those who did not (52.6 l h(-1) , P = 0.04). The CYP2B6*6 genotype and age, and their combined impact explained 40%, 30% and 60% of the variation in Css,k , respectively. Similar results were observed after higher doses. The CYP2B6*6 allele is associated with a substantial decrease in steady-state ketamine plasma clearance in chronic pain patients. The decreased clearance and resultant higher plasma concentrations may be associated with a higher incidence of ketamine adverse effects. © 2015 The British Pharmacological Society.

The acute effects of a low and high dose of oral L-arginine supplementation in young active males at rest.

PubMed

Forbes, Scott C; Bell, Gordon J

2011-06-01

L-arginine (2-amino-5-guanidinovaleric acid) is a conditionally essential amino acid. Intravenous (IV) administration of l-arginine invokes a large metabolic (nitrate/nitrite (NO(x))) and hormonal (growth hormone (GH), insulin-like growth factor 1 (IGF-1), and insulin) response; however, research examining oral l-arginine supplementation is conflicting, potentially owing to dose. The purpose of this study was examine a low and high dose of oral l-arginine on blood l-arginine, NO(x), GH, IGF-1, and insulin response. Fourteen physically active males (age: 25 ± 5 years; weight: 78.0 ± 8.5 kg; height: 179.4 ± 4.7 cm) volunteered to be in a randomized, double-blind, repeated-measures study. Following an overnight fast, an IV catheter was placed in a forearm vein and a resting blood sample was drawn at ∼0800 hours. Each subject was then provided 1 of 3 treatment conditions (placebo, low (0.075 g·kg(-1) of body mass), or high (0.15 g·kg(-1) of body mass of l-arginine)). Blood samples were drawn at 30, 60, 90, 120, and 180 min after consumption. l-arginine plasma concentrations significantly increased (p < 0.001) to a similar level at any time point in both the low- and high-dose conditions; there was no change over time in the placebo condition. There was no significant difference between conditions for NO(x), GH, IGF-1, or insulin. Based on these findings, a low dose of l-arginine was just as effective at increasing plasma l-arginine concentrations as a high dose; however, neither dose was able to promote a significant increase in NO(x), GH, IGF-1, or insulin at rest.

Effects of nonylphenol and ethinylestradiol on copper redhorse (Moxostoma hubbsi), an endangered species.

PubMed

Maltais, Domynick; Roy, Robert L

2014-10-01

The copper redhorse, Moxostoma hubbsi, is an endangered species endemic to Quebec. The presence of contaminants, in particular endocrine disrupting chemicals (EDCs), in its habitat has been advanced as partly responsible for the reproductive difficulties encountered by the species. In the present study, immature copper redhorse were exposed to the estrogenic surfactant nonylphenol (NP; 1, 10 and 50µg/l) and the synthetic estrogen 17α-ethinylestradiol (EE2; 10ng/l) for 21 days in a flow-through system. The endpoints investigated included general health indicators (hepatosomatic index and hematocrit), thyroid hormones, sex steroids, brain aromatase activity, plasma and mucus vitellogenin (VTG), cytochrome P4501A protein expression and ethoxyresorufin-O-deethylase activity, heat shock protein 70 (HSP70) and muscle acetylcholinesterase. Exposure to 10ng EE2/l significantly increased brain aromatase activity. Exposure to 50µg NP/l resulted in a significant reduction of plasma testosterone concentrations and a significant induction of hepatic HSP70 protein expression. NP at 50µg/l also induced plasma and mucus VTG. The presence of elevated VTG levels in the surface mucus of immature copper redhorse exposed to NP, and its correlation to plasma VTG, supports the use of mucus VTG as a non-invasive biomarker to evaluate copper redhorse exposure to EDCs in the environment and contribute to restoration efforts of the species. The results of the present study indicate that exposure to high environmentally relevant concentrations of NP and EE2 can affect molecular endpoints related to reproduction in the copper redhorse. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Nonlinear gyrokinetic simulations of the I-mode high confinement regime and comparisons with experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, A. E., E-mail: whitea@mit.edu; Howard, N. T.; Creely, A. J.

2015-05-15

For the first time, nonlinear gyrokinetic simulations of I-mode plasmas are performed and compared with experiment. I-mode is a high confinement regime, featuring energy confinement similar to H-mode, but without enhanced particle and impurity particle confinement [D. G. Whyte et al., Nucl. Fusion 50, 105005 (2010)]. As a consequence of the separation between heat and particle transport, I-mode exhibits several favorable characteristics compared to H-mode. The nonlinear gyrokinetic code GYRO [J. Candy and R. E. Waltz, J Comput. Phys. 186, 545 (2003)] is used to explore the effects of E × B shear and profile stiffness in I-mode and comparemore » with L-mode. The nonlinear GYRO simulations show that I-mode core ion temperature and electron temperature profiles are more stiff than L-mode core plasmas. Scans of the input E × B shear in GYRO simulations show that E × B shearing of turbulence is a stronger effect in the core of I-mode than L-mode. The nonlinear simulations match the observed reductions in long wavelength density fluctuation levels across the L-I transition but underestimate the reduction of long wavelength electron temperature fluctuation levels. The comparisons between experiment and gyrokinetic simulations for I-mode suggest that increased E × B shearing of turbulence combined with increased profile stiffness are responsible for the reductions in core turbulence observed in the experiment, and that I-mode resembles H-mode plasmas more than L-mode plasmas with regards to marginal stability and temperature profile stiffness.« less

Magnetic Field Measurements In Magnetized Plasmas Using Zeeman Broadening Diagnostics

NASA Astrophysics Data System (ADS)

Haque, Showera; Wallace, Matthew; Presura, Radu; Neill, Paul

2017-10-01

The Zeeman effect has been used to measure the magnetic field in high energy density plasmas. This method is limited when plasma conditions are such that the line broadening due to the high plasma density and temperature surpasses the Zeeman splitting. We have measured magnetic fields in magnetized laser plasmas under conditions where the Zeeman splitting was not spectrally resolved. The magnetic field strength was determined from the difference in widths of two doublet components, using an idea proposed by Tessarin et al. (2011). Time-gated spectra with one-dimensional space-resolution were obtained at the Nevada Terawatt Facility for laser plasmas created by 20 J, 1 ns Leopard laser pulses, and expanding in the azimuthal magnetic field produced by the 0.6 MA Zebra pulsed power generator. We explore the response of the Al III 4s 2S1/2 - 4p 2P1 / 2 , 3 / 2 doublet components to the external magnetic field spatially along the plasma. Radial magnetic field and electron density profiles were measured within the plasma plume. This work was supported by the DOE/OFES Grant DE-SC0008829 and DOE/NNSA contract DE-FC52-06NA27616.

Chronic inhibition of nitric oxide synthase augments the ACTH response to exercise

PubMed Central

Jankord, Ryan; McAllister, Richard M.; Ganjam, Venkataseshu K.; Laughlin, M. Harold

2009-01-01

Exercise can activate the hypothalamo-pituitary-adrenocortical (HPA) axis, and regular exercise training can impact how the HPA axis responds to stress. The mechanism by which acute exercise induces HPA activity is unclear. Therefore, the purpose of this study was to test the hypothesis that nitric oxide modulates the neuroendocrine component of the HPA axis during exercise. Female Yucatan miniature swine were treated with N-nitro-l-arginine methyl ester (l-NAME) to test the effect of chronic nitric oxide synthase (NOS) inhibition on the ACTH response to exercise. In addition, we tested the effect of NOS inhibition on blood flow to tissues of the HPA axis and report the effects of handling and treadmill exercise on the plasma concentrations of ACTH and cortisol. Chronic NOS inhibition decreased plasma NOx levels by 44%, increased mean arterial blood pressure by 46%, and increased expression of neuronal NOS in carotid arteries. Vascular conductance was decreased in the frontal cortex, the hypothalamus, and the adrenal gland. Chronic NOS inhibition exaggerated the ACTH response to exercise. In contrast, chronic NOS inhibition decreased the ACTH response to restraint, suggesting that the role of NO in modulating HPA activity is stressor dependent. These results demonstrate that NOS activity modulates the response of the neuroendocrine component of the HPA axis during exercise stress. PMID:19144752

Chronic inhibition of nitric oxide synthase augments the ACTH response to exercise.

PubMed

Jankord, Ryan; McAllister, Richard M; Ganjam, Venkataseshu K; Laughlin, M Harold

2009-03-01

Exercise can activate the hypothalamo-pituitary-adrenocortical (HPA) axis, and regular exercise training can impact how the HPA axis responds to stress. The mechanism by which acute exercise induces HPA activity is unclear. Therefore, the purpose of this study was to test the hypothesis that nitric oxide modulates the neuroendocrine component of the HPA axis during exercise. Female Yucatan miniature swine were treated with N-nitro-l-arginine methyl ester (l-NAME) to test the effect of chronic nitric oxide synthase (NOS) inhibition on the ACTH response to exercise. In addition, we tested the effect of NOS inhibition on blood flow to tissues of the HPA axis and report the effects of handling and treadmill exercise on the plasma concentrations of ACTH and cortisol. Chronic NOS inhibition decreased plasma NO(x) levels by 44%, increased mean arterial blood pressure by 46%, and increased expression of neuronal NOS in carotid arteries. Vascular conductance was decreased in the frontal cortex, the hypothalamus, and the adrenal gland. Chronic NOS inhibition exaggerated the ACTH response to exercise. In contrast, chronic NOS inhibition decreased the ACTH response to restraint, suggesting that the role of NO in modulating HPA activity is stressor dependent. These results demonstrate that NOS activity modulates the response of the neuroendocrine component of the HPA axis during exercise stress.

Large plasma-membrane depolarization precedes rapid blue-light-induced growth inhibition in cucumber

NASA Technical Reports Server (NTRS)

Spalding, E. P.; Cosgrove, D. J.

1989-01-01

Blue-light (BL)-induced suppression of elongation of etiolated Cucumis sativus L. hypocotyls began after a 30-s lag time, which was halved by increasing the fluence rate from 10 to 100 micromoles m-2 s-1. Prior to the growth suppression, the plasma-membrane of the irradiated cells depolarized by as much as 100 mV, then returned within 2-3 min to near its initial value. The potential difference measured with surface electrodes changed with an identical time course but opposite polarity. The lag time for the change in surface potential showed an inverse dependence on fluence rate, similar to the lag for the growth inhibition. Green light and red light caused neither the electrical response nor the rapid inhibition of growth. The depolarization by BL did not propagate to nonirradiated regions and exhibited a refractory period of about 10 min following a BL pulse. Fluence-response relationships for the electrical and growth responses provide correlational evidence that the plasma-membrane depolarization reflects an event in the transduction chain of this light-growth response.

Response surface methodology for the optimization of dispersive liquid-liquid microextraction of chloropropanols in human plasma.

PubMed

Gonzalez-Siso, Paula; Lorenzo, Rosa A; Regenjo, María; Fernández, Purificación; Carro, Antonia M

2015-10-01

Chloropropanols are processing toxicants with a potential risk to human health due to the increased intake of processed foods. A rapid and efficient method for the determination of three chloropropanols in human plasma was developed using ultrasound-assisted dispersive liquid-liquid microextraction. The method involved derivatization and extraction in one step followed by gas chromatography with tandem mass spectrometry analysis. Parameters affecting extraction, such as sample pH, ionic strength, type and volume of dispersive and extraction solvents were optimized by response surface methodology using a pentagonal design. The linear range of the method was 5-200 ng/mL for 1,3-dichloro-2-propanol, 10-200 ng/mL for 2,3-dichloro-2-propanol and 10-400 ng/mL for 3-chloropropane-1,2-diol with the determination coefficients between 0.9989 and 0.9997. The limits of detection were in the range of 0.3-3.2 ng/mL. The precision varied from 1.9 to 10% relative standard deviation (n = 9). The recovery of the method was between 91 and 101%. Advantages such as low consumption of organic solvents and short time of analysis make the method suitable for the biomonitoring of chloropropanols. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Terahertz Radiation from Laser Created Plasma by Applying a Transverse Static Electric Field

NASA Astrophysics Data System (ADS)

Fukuda, Takuya; Katahira, Koji; Yugami, Noboru; Sentoku, Yasuhiko; Sakagami, Hitoshi; Nagatomo, Hideo

2016-10-01

Terahertz (THz) radiation, which is emitted in narrow cone in the forward direction from laser created plasma has been observed by N.Yugami et al.. Additionally, Löffler et al. have observed that a significantly increased THz emission intensity in the forward direction when the transverse static electric field is applied to the plasma. The purpose of our study is to derive the mechanism of the THz radiation from laser created plasma by applying the transverse static electric field. To study the radiation mechanism, we conducted 2D-PIC simulation. With the static electric field of 10 kV/cm and gas density of 1020 cm-3, we obtain 1.2 THz single cycle pulse radiation, whose intensity is 1.3 ×105 W/cm2. The magnetic field called ``picket fence mode'' is generated in the laser created plasma. At the boundary surface between the plasma and vacuum, the magnetic field is canceled because eddy current flows. We conclude that the temporal behavior of the magnetic field at the boundary surface radiates the THz wave.

Blood pressure and endocrine responses of healthy subjects in cold pressor test after acutely increased dietary sodium intake.

PubMed

Arjamaa, O; Mäkinen, T; Turunen, L; Huttunen, P; Leppäluoto, J; Vuolteenaho, O; Rintamäki, H

2001-05-01

The objective of the study was to compare blood pressure and endocrine responses in a cold pressure test in young healthy subjects who had shown increased blood pressure during an acutely increased sodium intake. Subjects (n = 53) added 121 mmol sodium into their normal diet for one week. If the mean arterial pressure had increased by a minimum of 5 mmHg compared to the control measure, they were selected for the experiments. The selected subjects (n = 8) were given 121 mmol supplemental sodium d-1 for 14 days after which they immersed the right hand into a cold (+10 degrees C) water bath for 5 min. The blood pressure increased (P < 0.05) during the test and was independent of the sodium intake. The plasma noradrenaline increased from 2.41 +/- 0.38 nmol l-1 to 2.82 +/- 0.42 nmol l-1 (P < 0.05) with normal diet and from 1.85 +/- 0.29 nmol l-1 to 2.40 +/- 0.37 nmol l-1 (P < 0.05) with high sodium diet. The starting concentrations and the endpoint concentrations were statistically similar. The plasma levels of natriuretic peptides (NT-proANP, ANP and BNP) did not change during the test, and the concentrations were independent of the sodium diet. To conclude, acutely increased sodium intake does not change blood pressure or hormonal responses in a cold pressor test in young healthy subjects.

Early Changes in Clinical, Functional, and Laboratory Biomarkers in Workers at Risk of Indium Lung Disease

PubMed Central

Virji, M. Abbas; Trapnell, Bruce C.; Carey, Brenna; Healey, Terrance; Kreiss, Kathleen

2014-01-01

Rationale: Occupational exposure to indium compounds, including indium–tin oxide, can result in potentially fatal indium lung disease. However, the early effects of exposure on the lungs are not well understood. Objectives: To determine the relationship between short-term occupational exposures to indium compounds and the development of early lung abnormalities. Methods: Among indium–tin oxide production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. Relationships between plasma indium concentration and health outcome variables were evaluated using restricted cubic spline and linear regression models. Measurements and Main Results: Eighty-seven (93%) of 94 indium–tin oxide facility workers (median tenure, 2 yr; median plasma indium, 1.0 μg/l) participated in the study. Spirometric abnormalities were not increased compared with the general population, and few subjects had radiographic evidence of alveolar proteinosis (n = 0), fibrosis (n = 2), or emphysema (n = 4). However, in internal comparisons, participants with plasma indium concentrations ≥ 1.0 μg/l had more dyspnea, lower mean FEV1 and FVC, and higher median serum Krebs von den Lungen-6 and surfactant protein-D levels. Spline regression demonstrated nonlinear exposure response, with significant differences occurring at plasma indium concentrations as low as 1.0 μg/l compared with the reference. Associations between health outcomes and the natural log of plasma indium concentration were evident in linear regression models. Associations were not explained by age, smoking status, facility tenure, or prior occupational exposures. Conclusions: In indium–tin oxide facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, decreased spirometric parameters, and increased serum biomarkers of lung disease. PMID:25295756

A Genetic Response Score for Hydrochlorothiazide Use: Insights From Genomics and Metabolomics Integration.

PubMed

Shahin, Mohamed H; Gong, Yan; McDonough, Caitrin W; Rotroff, Daniel M; Beitelshees, Amber L; Garrett, Timothy J; Gums, John G; Motsinger-Reif, Alison; Chapman, Arlene B; Turner, Stephen T; Boerwinkle, Eric; Frye, Reginald F; Fiehn, Oliver; Cooper-DeHoff, Rhonda M; Kaddurah-Daouk, Rima; Johnson, Julie A

2016-09-01

Hydrochlorothiazide is among the most commonly prescribed antihypertensives; yet, <50% of hydrochlorothiazide-treated patients achieve blood pressure (BP) control. Herein, we integrated metabolomic and genomic profiles of hydrochlorothiazide-treated patients to identify novel genetic markers associated with hydrochlorothiazide BP response. The primary analysis included 228 white hypertensives treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. Genome-wide analysis was conducted using Illumina Omni 1 mol/L-Quad Chip, and untargeted metabolomics was performed on baseline fasting plasma samples using a gas chromatography-time-of-flight mass spectrometry platform. We found 13 metabolites significantly associated with hydrochlorothiazide systolic BP (SBP) and diastolic BP (DBP) responses (false discovery rate, <0.05). In addition, integrating genomic and metabolomic data revealed 3 polymorphisms (rs2727563 PRKAG2, rs12604940 DCC, and rs13262930 EPHX2) along with arachidonic acid, converging in the netrin signaling pathway (P=1×10(-5)), as potential markers, significantly influencing hydrochlorothiazide BP response. We successfully replicated the 3 genetic signals in 212 white hypertensives treated with hydrochlorothiazide and created a response score by summing their BP-lowering alleles. We found patients carrying 1 response allele had a significantly lower response than carriers of 6 alleles (∆SBP/∆DBP: -1.5/1.2 versus -16.3/-10.4 mm Hg, respectively, SBP score, P=1×10(-8) and DBP score, P=3×10(-9)). This score explained 11.3% and 11.9% of the variability in hydrochlorothiazide SBP and DBP responses, respectively, and was further validated in another independent study of 196 whites treated with hydrochlorothiazide (DBP score, P=0.03; SBP score, P=0.07). This study suggests that PRKAG2, DCC, and EPHX2 might be important determinants of hydrochlorothiazide BP response. © 2016 American Heart Association, Inc.

Modification of "Pressed" Atmospheres in Active Regions of Ultracool Stars

NASA Astrophysics Data System (ADS)

Zaitsev, V. V.; Kronshtadtov, P. V.; Stepanov, A. V.

2017-12-01

Ultracool stars usually have active regions, which is confirmed by their high-power radiofrequency emission modulated by the star axial rotation. The interpretation of this emission is commonly based on the electron cyclotron maser mechanism realized in the active regions. A plasma mechanism of radiofrequency emission is not considered, because ultracool star atmospheres are tightly "pressed" against the star surface, and the plasma frequency is much lower than the electron gyrofrequency ( f L ≪ f B) at the coronal levels. This paper explores active regions of ultracool stars for the possible existence of a system of coronal magnetic loops carrying electric current generated by photospheric convection. It is shown that current dissipation induces a temperature increase inside the loops to about 107 K, which causes an increase in the scale of height of the inhomogeneous atmosphere and, at the coronal levels, effectuates condition f L ≫ f B, at which the plasma mechanism of radiofrequency emission prevails over the electron cyclotron maser mechanism. The magnetic loop parameters, intensity of electric currents generated by the photospheric convection, and efficiency of plasma heating inside the magnetic loops are evaluated on the example of the brown dwarf TVLM513-46546. The scale of the height of the modified atmosphere, which appears to be comparable to the star radius, is calculated; it is shown that the soft X-ray flow created by the hot modified atmosphere inside a coronal magnetic loop is about equal to that observed for brown dwarf TVLM513-46546.

Perturbative tests of theoretical transport models using cold pulse and modulated electron cyclotron heating experiments

NASA Astrophysics Data System (ADS)

Kinsey, J. E.; Waltz, R. E.; DeBoo, J. C.

1999-05-01

It is difficult to discriminate between various tokamak transport models using standardized statistical measures to assess the goodness of fit with steady-state density and temperature profiles in tokamaks. This motivates consideration of transient transport experiments as a technique for testing the temporal response predicted by models. Results are presented comparing the predictions from the Institute for Fusion Studies—Princeton Plasma Physics Laboratory (IFS/PPPL), gyro-Landau-fluid (GLF23), Multi-mode (MM), Current Diffusive Ballooning Mode (CDBM), and Mixed-shear (MS) transport models against data from ohmic cold pulse and modulated electron cyclotron heating (ECH) experiments. In ohmically heated discharges with rapid edge cooling due to trace impurity injection, it is found that critical gradient models containing a strong temperature ratio (Ti/Te) dependence can exhibit behavior that is qualitatively consistent both spatially and temporally with experimental observation while depending solely on local parameters. On the DIII-D tokamak [J. L. Luxon and L. G. Davis, Fusion Technol. 8, 441 (1985)], off-axis modulated ECH experiments have been conducted in L-mode (low confinement mode) and the perturbed electron and ion temperature response to multiple heat pulses has been measured across the plasma core. Comparing the predicted Fourier phase of the temperature perturbations, it is found that no single model yielded agreement with both electron and ion phases for all cases. In general, it was found that the IFS/PPPL, GLF23, and MS models agreed well with the ion response, but not with the electron response. The CDBM and MM models agreed well with the electron response, but not with the ion response. For both types of transient experiments, temperature coupling between the electron and ion transport is found to be an essential feature needed in the models for reproducing the observed perturbative response.

Electrochemical study on the corrosion resistance of plasma nanocoated 316L stainless steel in albumin- and lysozyme-containing electrolytes

PubMed Central

Jones, John Eric; Chen, Meng; Chou, Ju; Yu, Qingsong

2017-01-01

The physiological corrosion resistance of plasma nanocoated 316L stainless steel was studied in protein-containing electrolytes using electrochemical methods. Plasma nanocoatings with thicknesses of 20–30 nm were deposited onto 316L stainless steel coupons in a glow discharge of trimethylsilane (TMS) or its mixture with oxygen gas under various gas ratios. The surface chemistries of the plasma nanocoatings were characterized using Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). Corrosion properties of the plasma nanocoated 316L stainless steel coupons were assessed using potentiodynamic polarization, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) in phosphate-buffered saline (PBS) electrolytes that contain bovine serum albumin (BSA) or lysozyme. It was found that BSA adsorption on the plasma nanocoated 316L coupons was heavily favored. BSA adsorption on the plasma nanocoating surfaces could block charge-transfer reactions between the electrolyte and 316L substrate, and thus stabilize the 316L substrates from further corrosion. In contrast, lysozyme adsorption on the plasma nanocoated specimens was not as pronounced and mildly influenced the corrosion properties of the plasma nanocoated 316L stainless steel. PMID:29422723

Particle Acceleration and Magnetic Field Generation in Electron-Positron Relativistic Shocks

NASA Technical Reports Server (NTRS)

Nishikawa, K.-I.; Hardee, P.; Richardson, G.; Preece, R.; Sol, H.; Fishman, G. J.

2004-01-01

Shock acceleration is an ubiquitous phenomenon in astrophysical plasmas. Plasma waves and their associated instabilities (e.g., Buneman, Weibel and other two-stream instabilities) created in collisionless shocks are responsible for particle (electron, positron, and ion) acceleration. Using a 3-D relativistic electromagnetic particle (REMP) code, we have investigated particle acceleration associated with a relativistic electron-positron jet front propagating into an ambient electron-positron plasma with and without initial magnetic fields. We find small differences in the results for no ambient and modest ambient magnetic fields. Simulations show that the Weibel instability created in the collisionless shock front accelerates jet and ambient particles both perpendicular and parallel to the jet propagation direction. The non-linear fluctuation amplitudes of densities, currents, electric, and magnetic fields in the electron-positron shock are larger than those found in the electron-ion shock studied in a previous paper. This comes from the fact that both electrons and positrons contribute to generation of the Weibel instability. Additionally, we have performed simulations with different electron skin depths. We find that growth times scale inversely with the plasma frequency, and the sizes of structures created by the Weibel instability scale proportional to the electron skin depth. This is the expected result and indicates that the simulations have sufficient grid resolution. While some Fermi acceleration may occur at the jet front, the majority of electron and positron acceleration takes place behind the jet front and cannot be characterized as Fermi acceleration. The simulation results show that the Weibel instability is responsible for generating and amplifying nonuniform, small-scale magnetic fields which contribute to the electron's (positron's) transverse deflection behind the jet head. This small scale magnetic field structure is appropriate to the generation of "jitter" radiation from deflected electrons (positrons) as opposed to synchrotron radiation. The jitter radiation has different properties than synchrotron radiation calculated assuming a a uniform magnetic field. The jitter radiation resulting from small scale magnetic field structures may be important for understanding the complex time structure and spectral evolution observed in gamma-ray bursts or other astrophysical sources containing relativistic jets and relativistic collisionless shocks.

Particle Acceleration and Magnetic Field Generation in Electron-Positron Relativistic Shocks

NASA Technical Reports Server (NTRS)

Nishikawa, K.-L.; Hardee, P.; Richardson, G.; Preece, R.; Sol, H.; Fishman, G. J.

2004-01-01

Shock acceleration is an ubiquitous phenomenon in astrophysical plasmas. Plasma waves and their associated instabilities (e.g., Buneman, Weibel and other two-stream instabilities) created in collisionless shocks are responsible for particle (electron, positron, and ion) acceleration. Using a 3-D relativistic electromagnetic particle (REMP) code, we have investigated particle acceleration associated with a relativistic electron-positron jet front propagating into an ambient electron-positron plasma with and without initial magnetic fields. We find small differences in the results for no ambient and modest ambient magnetic fields. Simulations show that the Weibel instability created in the collisionless shock front accelerates jet and ambient particles both perpendicular and parallel to the jet propagation direction. The non-linear fluctuation amplitudes of densities, currents, electric, and magnetic fields in the electron-positron shock are larger than those found in the electron-ion shock studied in a previous paper at the comparable simulation time. This comes from the fact that both electrons and positrons contribute to generation of the Weibel instability. Additionally, we have performed simulations with different electron skin depths. We find that growth times scale inversely with the plasma frequency, and the sizes of structures created by the Weibel instability scale proportional to the electron skin depth. This is the expected result and indicates that the simulations have sufficient grid resolution. While some Fermi acceleration may occur at the jet front, the majority of electron and positron acceleration takes place behind the jet front and cannot be characterized as Fermi acceleration. The simulation results show that the Weibel instability is responsible for generating and amplifying nonuniform: small-scale magnetic fields which contribute to the electron's (positron's) transverse deflection behind the jet head. This small scale magnetic field structure is appropriate to the generation of jitter radiation from deflected electrons (positrons) as opposed to synchrotron radiation. The jitter radiation has different properties than synchrotron radiation calculated assuming a a uniform magnetic field. The jitter radiation resulting from small scale magnetic field structures may be important for understanding the complex time structure and spectral evolution observed in gamma-ray bursts or other astrophysical sources containing relativistic jets and relativistic collisionless shocks.

Particle Acceleration and Magnetic Field Generation in Electron-Positron Relativistic Shocks

NASA Technical Reports Server (NTRS)

Nishikawa, K.-I.; Hardee, P.; Richardson, G.; Preece, R.; Sol, H.; Fishman, G. J.

2005-01-01

Shock acceleration is a ubiquitous phenomenon in astrophysical plasmas. Plasma waves and their associated instabilities (e.g., Buneman, Weibel, and other two-stream instabilities) created in collisionless shocks are responsible for particle (electron, positron, and ion) acceleration. Using a three-dimensional relativistic electromagnetic particle (REMP) code, we have investigated particle acceleration associated with a relativistic electron-positron jet front propagating into an ambient electron-positron plasma with and without initial magnetic fields. We find small differences in the results for no ambient and modest ambient magnetic fields. New simulations show that the Weibel instability created in the collisionless shock front accelerates jet and ambient particles both perpendicular and parallel to the jet propagation direction. Furthermore, the nonlinear fluctuation amplitudes of densities, currents, and electric and magnetic fields in the electron-positron shock are larger than those found in the electron-ion shock studied in a previous paper at a comparable simulation time. This comes from the fact that both electrons and positrons contribute to generation of the Weibel instability. In addition, we have performed simulations with different electron skin depths. We find that growth times scale inversely with the plasma frequency, and the sizes of structures created by tine Weibel instability scale proportionally to the electron skin depth. This is the expected result and indicates that the simulations have sufficient grid resolution. While some Fermi acceleration may occur at the jet front, the majority of electron and positron acceleration takes place behind the jet front and cannot be characterized as Fermi acceleration. The simulation results show that the Weibel instability is responsible for generating and amplifying nonuniform, small-scale magnetic fields, which contribute to the electron s (positron s) transverse deflection behind the jet head. This small- scale magnetic field structure is appropriate to the generation of "jitter" radiation from deflected electrons (positrons) as opposed to synchrotron radiation. The jitter radiation has different properties than synchrotron radiation calculated assuming a uniform magnetic field. The jitter radiation resulting from small-scale magnetic field structures may be important for understanding the complex time structure and spectral evolution observed in gamma-ray bursts or other astrophysical sources containing relativistic jets and relativistic collisionless shocks.

CHROMOSPHERIC NANOFLARES AS A SOURCE OF CORONAL PLASMA. II. REPEATING NANOFLARES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bradshaw, S. J.; Klimchuk, J. A., E-mail: stephen.bradshaw@rice.edu, E-mail: James.A.Klimchuk@nasa.gov

The million degree plasma of the solar corona must be supplied by the underlying layers of the atmosphere. The mechanism and location of energy release, and the precise source of coronal plasma, remain unresolved. In earlier work, we pursued the idea that warm plasma is supplied to the corona via direct heating of the chromosphere by nanoflares, contrary to the prevailing belief that the corona is heated in situ and the chromosphere is subsequently energized and ablated by thermal conduction. We found that single (low-frequency) chromospheric nanoflares could not explain the observed intensities, Doppler-shifts, and red/blue asymmetries in Fe xiimore » and xiv emission lines. In the present work, we follow up on another suggestion that the corona could be powered by chromospheric nanoflares that repeat on a timescale substantially shorter than the cooling/draining timescale. That is, a single magnetic strand is re-supplied with coronal plasma before the existing plasma has time to cool and drain. We perform a series of hydrodynamic experiments and predict the Fe xii and xiv line intensities, Doppler-shifts, and red/blue asymmetries. We find that our predicted quantities disagree dramatically with observations and fully developed loop structures cannot be created by intermediate- or high-frequency chromospheric nanoflares. We conclude that the mechanism ultimately responsible for producing coronal plasma operates above the chromosphere, but this does not preclude the possibility of a similar mechanism powering the chromosphere, extreme examples of which may be responsible for heating chromospheric plasma to transition region temperatures (e.g., type II spicules)« less

Insights on the Host Stress, Fear and Growth Responses to the Deoxynivalenol Feed Contaminant in Broiler Chickens

PubMed Central

Ghareeb, Khaled; Awad, Wageha A.; Sid-Ahmed, Omer E.; Böhm, Josef

2014-01-01

Mycotoxins pose an important danger to human and animal health. Poultry feeds are frequently contaminated with deoxynivalenol (DON) mycotoxin. It is thus of great importance to evaluate the effects of DON on the welfare related parameters in poultry industry. In the present study, the effects of contamination of broiler diet with 10 mg DON/kg feed on plasma corticosterone and heterophil to lymphocyte (H/L) ratio as indicators of stress, tonic immobility duration as an index for fear response and growth performance of broiler chickens were studied. In addition, the effect of a microbial feed additive either alone or in combination with DON contamination on these different aspects was also evaluated. The results showed that DON feeding significantly affected the welfare related parameters of broiler chickens. The feeding of DON contaminated diet resulted in an elevation of plasma corticosterone, higher H/L ratio and increased the fear levels as indicated by longer duration of tonic immobility reaction. Furthermore, DON reduced the body weight and body weight gain during the starter phase definitely at the second and third week. However, during grower phase, feeding of DON decreased the body weight at the fourth week and reduced the body gain at the fifth week. Addition of the microbial feed additive, a commercial antidote for DON mycotoxin, was able to overcome DON effects on stress index (H/L ratio), fearfulness and growth parameters of broilers. In conclusion, we showed for the first time that the DON feeding increased the underlying fearfulness and physiological stress responses of broilers and resulted in a reduction in the welfare status as indicated by higher plasma corticosterone, higher H/L ratio and higher fearfulness. Additionally, feeding the microbial feed additive was effective in reducing the adverse effects of DON on the bird's welfare and can improve the performance of broiler chickens. PMID:24498179

Insights on the host stress, fear and growth responses to the deoxynivalenol feed contaminant in broiler chickens.

PubMed

Ghareeb, Khaled; Awad, Wageha A; Sid-Ahmed, Omer E; Böhm, Josef

2014-01-01

Mycotoxins pose an important danger to human and animal health. Poultry feeds are frequently contaminated with deoxynivalenol (DON) mycotoxin. It is thus of great importance to evaluate the effects of DON on the welfare related parameters in poultry industry. In the present study, the effects of contamination of broiler diet with 10 mg DON/kg feed on plasma corticosterone and heterophil to lymphocyte (H/L) ratio as indicators of stress, tonic immobility duration as an index for fear response and growth performance of broiler chickens were studied. In addition, the effect of a microbial feed additive either alone or in combination with DON contamination on these different aspects was also evaluated. The results showed that DON feeding significantly affected the welfare related parameters of broiler chickens. The feeding of DON contaminated diet resulted in an elevation of plasma corticosterone, higher H/L ratio and increased the fear levels as indicated by longer duration of tonic immobility reaction. Furthermore, DON reduced the body weight and body weight gain during the starter phase definitely at the second and third week. However, during grower phase, feeding of DON decreased the body weight at the fourth week and reduced the body gain at the fifth week. Addition of the microbial feed additive, a commercial antidote for DON mycotoxin, was able to overcome DON effects on stress index (H/L ratio), fearfulness and growth parameters of broilers. In conclusion, we showed for the first time that the DON feeding increased the underlying fearfulness and physiological stress responses of broilers and resulted in a reduction in the welfare status as indicated by higher plasma corticosterone, higher H/L ratio and higher fearfulness. Additionally, feeding the microbial feed additive was effective in reducing the adverse effects of DON on the bird's welfare and can improve the performance of broiler chickens.

Sensitive LC-MS/MS Method for the Simultaneous Determination of Bendamustine and its Active Metabolite, γ-Hydroxybendamustine in Small Volume Mice and Dog Plasma and its Application to a Pharmacokinetic Study in Mice and Dogs.

PubMed

Chandrashekar, Devaraj V; Suresh, Ponnayyan S; Kumar, Rajnish; Bhamidipati, Ravi Kanth; Mullangi, Ramesh; Richter, Wolfgang; Srinivas, Nuggehally R

2017-09-01

A highly sensitive, specific and rapid LC-ESI-MS/MS method has been developed and validated for the simultaneous quantification of bendamustine (BM) and γ-hydroxybendamustine (HBM) in small volume (20 µL) mice and dog plasma using phenacetin as an internal standard (IS) as per regulatory guidelines. Both the analytes and IS were extracted from mice and dog plasma using a liquid-liquid extraction method. Chromatography was achieved on Atlantis dC 18 column using an isocratic mobile phase (0.2% formic acid:acetonitrile, 25:75) at a flow rate of 0.40 mL/min. The total chromatographic run time was 3.0 min and the elution of BM, HBM and IS occurred at ~1.2, 1.2 and 2.0 min, respectively. A linear response function was established 0.11-518 ng/mL for both the analytes in mice and dog plasma. The intra- and inter-day accuracy and precisions were in the range of 3.46-12.9 and 3.63-8.23%; 1.15-9.00 and 7.86-9.49% for BM and HBM, respectively in mice plasma and 2.15-6.49 and 1.73-13.1%; 4.35-13.9 and 4.33-10.5% for BM and HBM, respectively in dog plasma. This novel method has been applied to a pharmacokinetic study in mice and dogs. © Georg Thieme Verlag KG Stuttgart · New York.

The role of selenium in iodine metabolism in children with goiter.

PubMed Central

Zagrodzki, P; Szmigiel, H; Ratajczak, R; Szybinski, Z; Zachwieja, Z

2000-01-01

Possible interactions between selenium and iodine metabolism were investigated in 7- to 16-year-old children with goiter (n = 136) living in southeastern Poland in iodine-deficient areas influenced by a sulfur industry. The Se-iodine interactions in these children were compared to the interactions in children from outside of that region (n = 38). Blood selenium (BSe) concentration and plasma glutathione peroxidase activity were much lower in the study group (64.1 +/- 15.7 microg/L; 111.0 +/- 27.6 U/L) than in the control group (85.3 +/- 19.6 microg/L; 182.4 +/- 35.6 U/L). Almost all of the data [plasma thyroid-stimulating hormone (TSH) concentration, plasma free thyroxine (fT(4)) concentration] fell within the reference limits. There was no statistically significant difference between the control and the study groups with respect to fT(4) and TSH. However, statistically significant differences of fT(4) and TSH in the study group were revealed between females belonging to the lower (n = 21; fT(4), 16.1 +/- 3.3 pmol/L; TSH, 1.83 +/- 1.05 mU/L) and upper Se quartiles (n = 24; fT(4), 14.5 +/- 2.2 pmol/L; TSH, 1. 26 +/- 0.90 mU/L), p < 0.05. Neither group differed in iodine in urine concentration, age, and body mass index. The difference in fT(4) concentrations can be attributed to an Se deficiency. The relationship exists only for females, which suggests a sex-linked hormonal response to concomitant Se and iodine deficiencies. Images Figure 1 Figure 2 PMID:10620526

Adhesive Stretchable Printed Conductive Thin Film Patterns on PDMS Surface with an Atmospheric Plasma Treatment.

PubMed

Li, Chun-Yi; Liao, Ying-Chih

2016-05-11

In this study, a plasma surface modification with printing process was developed to fabricate printed flexible conductor patterns or devices directly on polydimethylsiloxane (PDMS) surface. An atmospheric plasma treatment was first used to oxidize the PDMS surface and create a hydrophilic silica surface layer, which was confirmed with photoelectron spectra. The plasma operating parameters, such as gas types and plasma powers, were optimized to obtain surface silica layers with the longest lifetime. Conductive paste with epoxy resin was screen-printed on the plasma-treated PDMS surface to fabricate flexible conductive tracks. As a result of the strong binding forces between epoxy resin and the silica surface layer, the printed patterns showed great adhesion on PDMS and were undamaged after several stringent adhesion tests. The printed conductive tracks showed strong mechanical stability and exhibited great electric conductivity under bending, twisting, and stretching conditions. Finally, a printed pressure sensor with good sensitivity and a fast response time was fabricated to demonstrate the capability of this method for the realization of printed electronic devices.

Patients with Nonalcoholic Fatty Liver Disease Have a Low Response Rate to Vitamin D Supplementation.

PubMed

Dasarathy, Jaividhya; Varghese, Rony; Feldman, Abram; Khiyami, Amer; McCullough, Arthur J; Dasarathy, Srinivasan

2017-10-01

Background: Hypovitaminosis D is associated with an increased severity of nonalcoholic fatty liver disease (NAFLD), but reports on the response to cholecalciferol (vitamin D 3 ) supplementation are conflicting. Objective: The objective of this study was to determine if standard vitamin D 3 supplementation is effective in NAFLD with hypovitaminosis D. Methods: Sixty-five well-characterized adults [age (mean ± SD): 51.6 ± 12.3 y] with biopsy-proven NAFLD were screened. Forty-two patients (the ratio of men to women was 13:29) had hypovitaminosis D (plasma 25-hydroxyvitamin D [25(OH)D] <30 ng/mL). An observational study was performed in NAFLD patients with hypovitaminosis D treated with 2000 IU cholecalciferol (vitamin D 3 ) daily for 6 mo per clinical practice. Plasma 25(OH)D, hepatic and metabolic panels, and metabolic syndrome components were assessed before and after cholecalciferol supplementation. Body composition was measured by using bioelectrical impedance analysis. The primary outcome measure was plasma 25(OH)D ≥30 ng/mL at the end of the study. Secondary outcomes included change in serum transaminases, fasting plasma glucose, and insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Chi-square, Student's t tests, correlation coefficient, and multivariate analysis were performed. Results: Twenty-six (61.9%) patients had nonalcoholic steatohepatitis (NASH), and 16 (38.1%) had hepatic steatosis. After 6 mo of cholecalciferol supplementation, plasma 25(OH)D ≥30 ng/mL was observed in 16 subjects (38.1%; responders) whereas the remaining 26 patients (61.9%) were nonresponders with plasma 25(OH)D <30 ng/mL. Significantly fewer ( P < 0.01) patients with NASH were responders (4 of 26, 15.4%) than those with hepatic steatosis (12 of 16, 75%). Baseline fasting serum alanine aminotransferase, plasma glucose, and HOMA-IR were similar in the responders and nonresponders, but the NASH score on the liver biopsy was lower (16.5%) in the responders ( P < 0.001). Nonresponders had a higher fat mass (10.5%) and lower fat-free mass (10.4%) than responders did. End-of-treatment alanine aminotransferase and HOMA-IR improved only in responders. The baseline HOMA-IR and histological NASH score were independent predictors of nonresponse to cholecalciferol supplementation. Conclusions: Daily supplementation with 2000 IU cholecalciferol for 6 mo did not correct hypovitaminosis D in the majority of patients with NASH. Further studies are needed to determine if higher doses are effective. This trial was registered at clinicaltrials.gov as 13-00153. © 2017 American Society for Nutrition.

[Differences of blood plasma renin activity, angiotensin II and aldosterone levels in essential or secondary hypertension].

PubMed

Song, Ai-ling; Zeng, Zheng-pei; Tong, An-li; Lu, Lin; Chen, Shi; Li, Ming; Fu, Chun-li; Wang, Yong-hui; Sun, Mei-li

2012-04-01

To study on the difference of plasma renin activity (PRA), angiotensin II (Ang II), and aldosterone levels in patients with essential hypertension (EH) or primary aldosteronism (PA) or pheochromocytoma (PHEO), and to analyze the sensitivity and specificity on the diagnosis of PA among patients with hypertension with aldosterone/PRA ratio (ARR). The plasma aldosterone, Ang II and PRA concentrations in supine and upright positions were measured by radioimmunoassay from 413 patients including idiopathic hyperaldosteronism (IHA, n = 111), aldosterone-producing adenoma (APA, n = 118), PHEO (n = 98) and EH (n = 86). ARR was calculated. Plasma aldosterone concentrations in both of supine and upright positions in PHEO group [374 (294, 465) pmol/L and 629 (449, 997) pmol/L] and PA group [471 (346, 632) pmol/L and 673 (499, 825) pmol/L] were higher than those in EH group [277 (224, 332) pmol/L and 427 (341, 501) pmol/L] (P < 0.01). They were also higher in APA group [576 (416, 731) pmol/L and 726 (554, 906) pmol/L] than those in IHA group [399 (313, 504) pmol/L and 609 (485, 776) pmol/L] (P < 0.01). Ang II levels in both positions were lower in PA group [43.2 (26.4, 74.4) ng/L and 60.1 (38.5, 103.6) ng/L] than in EH group [56.7 (43.3, 78.9) ng/L and 84.3 (61.3, 108.4) ng/L] or PHEO group [54.3 (29.9, 101.5) ng/L and 102.8 (49.9, 167.0) ng/L] (all P values < 0.01), and there was no difference between IHA and APA group (P > 0.05). The PRA level in both positions of each group were PHEO group [0.3 (0.2, 1.0) µg · L(-1) · h(-1) and 1.4 (0.6, 3.4) µg · L(-1) · h(-1)] > EH group [0.2 (0.1, 0.4) µg · L(-1) · h(-1) and 0.6 (0.4, 1.0) µg · L(-1) · h(-1)] (P < 0.01) > PA group [0.1 (0.1, 0.1) µg · L(-1) · h(-1) and 0.2 (0.1, 0.3) µg · L(-1) · h(-1)] (P < 0.01), and APA group [0.1 (0.1, 0.1) µg · L(-1) · h(-1) and 0.1 (0.1, 0.3) µg · L(-1) · h(-1)] < IHA group [0.1 (0.1, 0.2) µg · L(-1) · h(-1) and 0.2 (0.1, 0.3) µg · L(-1) · h(-1)] (supine P < 0.01; upright P < 0.05). APA was divided into 2 types with renin-Ang II-responsive APA (n = 26) and unresponsive APA (n = 92). The plasma aldosterone concentration was lower in supine position but higher in upright position in renin-Ang II-responsive APA than in unresponsive APA patients. ARR in upright was higher in PA group (P < 0.01) but lower in PHEO group (P < 0.05) compared with EH. ARR was higher in APA than in IHA (P < 0.01). The sensitivity and specificity of ARR as 40 (aldosterone unit: ng/dl; PRA unit: µg · L(-1) · h(-1); its value should multiply 27.7 when transferred to pmol/L, simili) were 93% and 76%, respectively. The levels of PRA, Ang II and aldosterone from patients with EH, PA and PHEO are significant different. ARR as 40 in upright position could be used for PA screening cutoff point.

Amino acid transmitters in patients with headache during the acute phase of cerebrovascular ischemic disease.

PubMed

Castillo, J; Martínez, F; Corredera, E; Aldrey, J M; Noya, M

1995-11-01

The pathophysiology of headache occurring at stroke onset is unknown. Migraine and ischemia share an excessive release of neuroexcitatory amino acids. Inhibitory amino acids also may be implicated in both diseases. We investigated whether fluctuations of these amino acids occur in headache accompanying cerebral infarction. We studied 100 patients with infarction in the territory of the middle cerebral artery. Neurological impairment was assessed using the Canadian Neurological Scale and Barthel Index. Size of infarction was determined with CT. Twenty-eight patients developed headache. Glutamate, aspartate, and taurine were quantified in blood and cerebrospinal fluid (CSF) within 24 hours of stroke onset with cationic exchange chromatography. Stroke subtypes, size of infarct on CT, and clinical scales were similar in patients with and without headache. Plasma glutamate level was 321.14 +/- 149.53 mumol/L in patients with headache and 233 +/- 107.23 mumol/L in those without headache (P < .005). Glutamate in CSF was higher in patients with headache (4.6 +/- 1.49 mumol/L) than in patients without headache (3.11 +/- 1.18 mumol/L) (P < .001). Aspartate concentrations in plasma and CSF were similar in both groups. Taurine concentrations in plasma were 103.10 +/- 52.82 mumol/L and 177.49 +/- 90.92 mumol/L in headache and nonheadache patients, respectively (P < .001). Taurine levels in CSF were 5.42 +/- 2.42 mumol/L in patients with headache and 9.27 +/- 5.31 mumol/L in those without headache (P < .001). No significant correlation was found between amino acid levels in plasma or CSF and size of infarction. Amino acid neurotransmitters play a role in the pathophysiology of headache that occurs at the onset of stroke. The ischemic penumbral area, more than the infarction itself, may cause a state of cortical hyperexcitability that would be responsible for the cortical release of amino acids and the induction of headache by altering pain perception mechanisms.

Responses to handling and confinement stressors in juvenile great sturgeon Huso huso.

PubMed

Falahatkar, B; Poursaeid, S; Shakoorian, M; Barton, B

2009-09-01

The effects of acute stressors on physiological responses of juvenile great sturgeon or beluga Huso huso L. were investigated in two experiments. In the first experiment, fish were handled by placing them in containers at either low density (LD, one fish l(-1)) or high density (HD, four fish l(-1)) for 60 s. Concentrations of plasma cortisol, glucose and lactate were determined from blood collected at 0, 1, 3, 6 and 12 h after application of the stressor. Plasma cortisol concentrations increased after the disturbance in H. huso from both handling treatments, but changes were not significant. Plasma glucose rose significantly by 22.9 and 31.6% in LD and HD handling treatments, respectively, after 3 h. Significant increases in plasma lactate occurred within 1 h in both treatment groups, but that of the HD group was much higher. In the second experiment, fish were held at two different densities, LD (2 kg m(-2) tank bottom surface area) and HD (7 kg m(-2)), for 8 weeks and then subjected to an aerial emersion handling stressor in a net for 60 s; blood samples were taken before handling (resting, 0 h) and at 1, 3, 6 and 9 h after handling. Plasma cortisol increased significantly in fish from the HD treatment from 8.8 +/- 0.3 to 19.2 +/- 2.4 ng ml(-1) (mean +/-s.e.) by 1 h after stress, but post-handling changes in the LD group were not significant. Significant increases in both plasma glucose and lactate were observed by 1 h in both treatment groups, with peak levels of plasma glucose evident at 3 h [69.4 +/- 2.9 and 60.9 +/- 1.7 mg dl(-1) (mean +/-s.e.) in LD and HD groups, respectively]. Plasma glucose levels were significantly higher in the LD group than in the HD group at 3 and 6 h. Post-handling haemoglobin content increased by 1 h and white blood cell numbers were reduced by 3 and 6 h in the HD treatment group compared with resting values, but changes in these blood features in the LD group were not significant. Acute handling did not affect haematocrit in either treatment. The results suggest that H. huso is relatively resistant to handling and confinement, and could tolerate normal hatchery practices associated with aquaculture. Because changes in cortisol concentrations were relatively low compared with those in most teleosts, glucose and lactate concentrations may be more useful as stress indicators in juvenile H. huso. This study also demonstrated that prior exposure to a chronic stressor, specifically high stocking density, could alter the physiological response to subsequent acute handling in H. huso.

Effect of rotating electric field on 3D complex (dusty) plasma

NASA Astrophysics Data System (ADS)

Wörner, L.; Nosenko, V.; Ivlev, A. V.; Zhdanov, S. K.; Thomas, H. M.; Morfill, G. E.; Kroll, M.; Schablinski, J.; Block, D.

2011-06-01

The effect of rotating electric field on 3D particle clusters suspended in rf plasma was studied experimentally. Spheroidal clusters were suspended inside a glass box mounted on the lower horizontal rf electrode, with gravity partially balanced by thermophoretic force. Clusters rotated in the horizontal plane, in response to rotating electric field that was created inside the box using conducting coating on its inner surfaces ("rotating wall" technique). Cluster rotation was always in the direction of applied field and had a shear in the vertical direction. The angular speed of rotation was 104-107 times lower than applied frequency. The experiment is compared to a recent theory.

Determination of erythromycin in human plasma, using column liquid chromatography with a polymeric packing material, alkaline mobile phase and amperometric detection.

PubMed

Nilsson, L G; Walldorf, B; Paulsen, O

1987-12-25

A method based on column liquid chromatography was developed for determination of plasma concentrations of erythromycin. PRP-1, a polymeric type of packing material suitable for chromatography and amperometric detection at high pH, was used. The effect of pH on the column performance and on the electrochemical response was studied. A pH of ca. 10 was found to be optimal. After extraction with tert.-butyl methyl ether, plasma concentrations down to 0.2 mumol/l could be measured, using automated sample injection. Oleandomycin was used as internal standard. The method was used for determination of plasma concentrations in a pharmacokinetic study under steady-state conditions.

Absence of detectable immunoreactive alpha melanocyte stimulating hormone in plasma in various types of Cushing's disease.

PubMed

Croughs, R J; Thijssen, J H; Mol, J A

1991-03-01

We have measured alpha-MSH in plasma of normal subjects and subjects with various diseases of the pituitary-adrenocortical system using a radioimmunoassay with a sensitivity of 1.2 pmol/l. No alpha-MSH could be detected in plasma of normal subjects (n = 6), in plasma of patients with Addison's disease (n = 3), Nelson's syndrome (n = 2), bromocriptine responsive (n = 2) and unresponsive (n = 5) Cushing's disease and in plasma of psychiatric patients on chronic treatment with the dopamine antagonist haloperidol (n = 5). Plasma alpha-MSH remained undetectable in 2 patients with Cushing's disease after iv injection of 60 micrograms/kg haloperidol. In contrast, alpha-MSH was detectable in plasma of normal dogs (n = 2) and dogs with pituitary dependent hyperadrenocorticism (n = 2), whereas the iv injection of halo peridol was associated with a rise of plasma alpha-MSH. Thus we are unable to detect circulating alpha-MSH in man despite the use of a sensitive radioimmunoassay.

Effect of cigar smoking on carboxyhaemoglobin and plasma nicotine concentrations in primary pipe and cigar smokers and ex-cigarette smokers

PubMed Central

Turner, J A McM; Sillett, R W; McNicol, M W

1977-01-01

Five ex-cigarette smokers and five primary pipe and cigar smokers each smoked a large cigar. Carboxyhaemoglobin (COHb) and plasma nicotine levels were measured. In the ex-cigarette smokers mean COHb rose from 2·9% to 9·6% and plasma nicotine from 79·0 nmol/l to 281 nmol/l (12·8-45·6 ng/ml). This response was similar to that of cigarette smokers smoking cigarettes, which indicated that the subjects had inhaled and absorbed significant amounts of nicotine. In the primary pipe and cigar smokers the mean COHb rose from 0·8% to 1·0% and the plasma nicotine from 21 nmol/l to 32 nmol/l (3·4-5·2 ng/ml), indicating neither significant inhalation nor significant nicotine absorption. Since ex-cigarette smokers do not seem to lose their habit of inhaling when they change to cigars, measures aimed at persuading smokers to switch to cigars will have little effect on their health. Pipe and cigar smokers who have never smoked cigarettes do not inhale, which probably accounts for their reduced incidence of coronary heart disease and lung cancer. But they also appear not to absorb nicotine, which suggests that nicotine is absorbed largely from the lung and that the buccal mucosa is unimportant. It also raises the interesting question of why primary pipe and cigar smokers do smoke. PMID:589225

Economical impact of plasma fractionation project in Iran on affordability of plasma-derived medicines.

PubMed

Cheraghali, A M; Aboofazeli, R

2009-12-01

In Iran all transfusion services are concentrated under authority of one public and centralized transfusion organization which has created the opportunity of using plasma produced in its blood centers for fractionation. In 2008 voluntary and non remunerated Iranian donors donated 1.8 million units of blood. This indicates a 25/1000 donation index. After responding to the needs for fresh plasma and cryoprecipitate each year about 150000 L of recovered plasma are reserved for fractionation. In an attempt to improve both blood safety profile and availability and affordability of plasma derived medicines, Iran's national transfusion service has entered into a contract fractionation agreement for surplus of plasma produced from donated blood by voluntary non remunerated donors. In order to ensure safety of product produced, Iran has chosen to collaborate with international fractionators based in highly regulated countries. The main objective of this study was to evaluate the impact of contract plasma fractionation on the affordability of the plasma derived medicines in Iran. During 2006-2008, Iran's contract fractionation project was able to produce 46%, 18% and 6% of IVIG, Albumin and FVIII consumed in Iran's market, respectively. In contrary to IVIG and Albumin, due to fairly high consumption of FVIII in Iran, the role of fractionation project in meeting the needs to FVIII was not substantial. However, Iran's experience has shown that contract plasma fractionation, through direct and indirect effects on price of plasma derived medicines, could substantially improve availability and affordability of such products in national health care system.

Colloidal lithography nanostructured Pd/PdO x core-shell sensor for ppb level H2S detection.

PubMed

Benedict, Samatha; Lumdee, Chatdanai; Dmitriev, Alexandre; Anand, Srinivasan; Bhat, Navakanta

2018-06-22

In this work we report on plasma oxidation of palladium (Pd) to form reliable palladium/palladium oxide (Pd/PdO x ) core-shell sensor for ppb level H 2 S detection and its performance improvement through nanostructuring using hole-mask colloidal lithography (HCL). The plasma oxidation parameters and the sensor operating conditions are optimized to arrive at a sensor device with high sensitivity and repeatable response for H 2 S. The plasma oxidized palladium/palladium oxide sensor shows a response of 43.1% at 3 ppm H 2 S at the optimum operating temperature of 200 °C with response and recovery times of 24 s and 155 s, respectively. The limit of detection (LoD) of the plasma oxidised beam is 10 ppb. We further integrate HCL, a bottom-up and cost-effective process, to create nanodiscs of fixed diameter of 100 nm and varying heights (10, 15 and 20 nm) on 10 nm thin Pd beam which is subsequently plasma oxidized to improve the H 2 S sensing characteristics. The nanostructured Pd/PdO x sensor with nanodiscs of 100 nm diameter and 10 nm height shows an enhancement in sensing performance by 11.8% at same operating temperature and gas concentration. This nanostructured sensor also shows faster response and recovery times (15 s and 100 s, respectively) compared to the unstructured Pd/PdO x counterpart together with an experimental LoD of 10 ppb and the estimated limit going all the way down to 2 ppb. Material characterization of the fabricated Pd/PdO x sensors is done using UV-vis spectroscopy and x-ray photoemission spectroscopy.

Colloidal lithography nanostructured Pd/PdO x core–shell sensor for ppb level H2S detection

NASA Astrophysics Data System (ADS)

Benedict, Samatha; Lumdee, Chatdanai; Dmitriev, Alexandre; Anand, Srinivasan; Bhat, Navakanta

2018-06-01

In this work we report on plasma oxidation of palladium (Pd) to form reliable palladium/palladium oxide (Pd/PdO x ) core–shell sensor for ppb level H2S detection and its performance improvement through nanostructuring using hole-mask colloidal lithography (HCL). The plasma oxidation parameters and the sensor operating conditions are optimized to arrive at a sensor device with high sensitivity and repeatable response for H2S. The plasma oxidized palladium/palladium oxide sensor shows a response of 43.1% at 3 ppm H2S at the optimum operating temperature of 200 °C with response and recovery times of 24 s and 155 s, respectively. The limit of detection (LoD) of the plasma oxidised beam is 10 ppb. We further integrate HCL, a bottom-up and cost-effective process, to create nanodiscs of fixed diameter of 100 nm and varying heights (10, 15 and 20 nm) on 10 nm thin Pd beam which is subsequently plasma oxidized to improve the H2S sensing characteristics. The nanostructured Pd/PdO x sensor with nanodiscs of 100 nm diameter and 10 nm height shows an enhancement in sensing performance by 11.8% at same operating temperature and gas concentration. This nanostructured sensor also shows faster response and recovery times (15 s and 100 s, respectively) compared to the unstructured Pd/PdO x counterpart together with an experimental LoD of 10 ppb and the estimated limit going all the way down to 2 ppb. Material characterization of the fabricated Pd/PdO x sensors is done using UV–vis spectroscopy and x-ray photoemission spectroscopy.

Method of making a coating of a microtextured surface

DOEpatents

Affinito, John D [Tucson, AZ; Graff, Gordon L [West Richland, WA; Martin, Peter M [Kennewick, WA; Gross, Mark E [Pasco, WA; Burrows, Paul E [Kennewick, WA; Sapochak, Linda S [Henderson, NV

2004-11-02

A method for conformally coating a microtextured surface. The method includes flash evaporating a polymer precursor forming an evaporate, passing the evaporate to a glow discharge electrode creating a glow discharge polymer precursor plasma from the evaporate, cryocondensing the glow discharge polymer precursor plasma on the microtextured surface and crosslinking the glow discharge polymer precursor plasma thereon, wherein the crosslinking resulting from radicals created in the glow discharge polymer precursor plasma.

Demonstration of a positron beam-driven hollow channel plasma wakefield accelerator

NASA Astrophysics Data System (ADS)

Gessner, Spencer; Adli, Erik; Allen, James M.; An, Weiming; Clarke, Christine I.; Clayton, Chris E.; Corde, Sebastien; Delahaye, J. P.; Frederico, Joel; Green, Selina Z.; Hast, Carsten; Hogan, Mark J.; Joshi, Chan; Lindstrøm, Carl A.; Lipkowitz, Nate; Litos, Michael; Lu, Wei; Marsh, Kenneth A.; Mori, Warren B.; O'Shea, Brendan; Vafaei-Najafabadi, Navid; Walz, Dieter; Yakimenko, Vitaly; Yocky, Gerald

2016-06-01

Plasma wakefield accelerators have been used to accelerate electron and positron particle beams with gradients that are orders of magnitude larger than those achieved in conventional accelerators. In addition to being accelerated by the plasma wakefield, the beam particles also experience strong transverse forces that may disrupt the beam quality. Hollow plasma channels have been proposed as a technique for generating accelerating fields without transverse forces. Here we demonstrate a method for creating an extended hollow plasma channel and measure the wakefields created by an ultrarelativistic positron beam as it propagates through the channel. The plasma channel is created by directing a high-intensity laser pulse with a spatially modulated profile into lithium vapour, which results in an annular region of ionization. A peak decelerating field of 230 MeV m-1 is inferred from changes in the beam energy spectrum, in good agreement with theory and particle-in-cell simulations.

Demonstration of a positron beam-driven hollow channel plasma wakefield accelerator

PubMed Central

Gessner, Spencer; Adli, Erik; Allen, James M.; An, Weiming; Clarke, Christine I.; Clayton, Chris E.; Corde, Sebastien; Delahaye, J. P.; Frederico, Joel; Green, Selina Z.; Hast, Carsten; Hogan, Mark J.; Joshi, Chan; Lindstrøm, Carl A.; Lipkowitz, Nate; Litos, Michael; Lu, Wei; Marsh, Kenneth A.; Mori, Warren B.; O'Shea, Brendan; Vafaei-Najafabadi, Navid; Walz, Dieter; Yakimenko, Vitaly; Yocky, Gerald

2016-01-01

Plasma wakefield accelerators have been used to accelerate electron and positron particle beams with gradients that are orders of magnitude larger than those achieved in conventional accelerators. In addition to being accelerated by the plasma wakefield, the beam particles also experience strong transverse forces that may disrupt the beam quality. Hollow plasma channels have been proposed as a technique for generating accelerating fields without transverse forces. Here we demonstrate a method for creating an extended hollow plasma channel and measure the wakefields created by an ultrarelativistic positron beam as it propagates through the channel. The plasma channel is created by directing a high-intensity laser pulse with a spatially modulated profile into lithium vapour, which results in an annular region of ionization. A peak decelerating field of 230 MeV m−1 is inferred from changes in the beam energy spectrum, in good agreement with theory and particle-in-cell simulations. PMID:27250570

The effects of high environmental ammonia on the structure of rainbow trout hierarchies and the physiology of the individuals therein.

PubMed

Grobler, Josias M B; Wood, Chris M

2018-02-01

Our goals were: (i) to determine whether sublethal concentrations of water-borne ammonia would prevent the formation of a dominance hierarchy, or alter its structure, in groups of 4 juvenile trout; (ii) to investigate the behavioral and physiological responses of individuals of different social rank exposed to a concentration of ammonia that still allowed hierarchy formation. Social hierarchies were created by using a technique in which a food delivery system that created competition also served to isolate individual fish for respirometry. Groups of 4 fish were exposed to elevated ammonia (NH 4 HCO 3 ) 12 h before first feeding; aggression was recorded by video camera during morning feedings. Experimental ammonia concentrations were 700, 1200 and 1500 μmol L -1 at pH 7.3, 12 °C (9.8, 16.8, and 21.0 mg L -1 as total ammonia-N, or 0.0515, 0.0884, and 0.1105 mg L -1 as NH 3 -N). Aggression was severely reduced by 1200 and abolished by 1500 μmol L -1 total ammonia, such that hierarchies did not form. However, groups exposed to 700 μmol L -1 total ammonia still formed stable hierarchies but displayed lower levels of aggression in comparison to control hierarchies. Exposure continued for 11 days. Physiological parameters were recorded on day 5 (end of period 1) and day 10 (end of period 2), while feeding and plasma cortisol were measured on day 11. In control hierarchies, dominant (rank 1) trout generally exhibited higher growth rates, greater increases in condition factor, higher food consumption, and lower cortisol levels than did fish of ranks 2, 3, and 4. In comparison to controls, the 700 μmol L -1 total ammonia hierarchies generally displayed lower growth, lower condition factor increases, lower O 2 consumption, lower cortisol levels, but similar feeding patterns, with smaller physiological differences amongst ranks during period 1. Effects attenuated during period 2, as aggression and physiological measures returned towards control levels, indicating both behavioral and physiological acclimation to ammonia. These disturbances in social behavior and associated physiology occurred at an ammonia concentration in the range of regulatory significance and relevance to aquaculture. Copyright © 2017 Elsevier B.V. All rights reserved.

Simultaneous determination of antidementia drugs in human plasma for therapeutic drug monitoring.

PubMed

Noetzli, Muriel; Choong, Eva; Ansermot, Nicolas; Eap, Chin B

2011-04-01

A simple liquid chromatography mass spectrometry method was developed and validated for the simultaneous determination of antidementia drugs, including donepezil, galantamine, rivastigmine and its major metabolite, NAP 226-90, and memantine. A solid phase extraction procedure with a mixed-mode sorbent was used to isolate the drugs from 0.5 mL human plasma. Reverse phase chromatographic separation of the compounds was obtained with a gradient elution of an ammonium acetate buffer at pH 9.3 and acetonitrile and the analytes were detected by mass spectrometry in the single ion monitoring mode. The method was validated according to the recommendations of the Food and Drug Administration, including assessment of trueness (-8.0% to +10.7%), imprecision (repeatability: 1.1-4.9%, intermediate imprecision: 2.1-8.5%), selectivity and matrix effects variability (less than 6%) as well as short- and long-term stability in plasma. The calibration ranges were from 1 ng/mL to 300 ng/mL (rivastigmine and memantine) and 2 ng/mL to 300 ng/mL (donepezil, galantamine, and NAP 226-90). The method was successfully applied to patients' samples and might contribute to evaluate whether a therapeutic drug monitoring-guided dose adjustment of antidementia drugs could contribute to minimize the risk of adverse reactions and to increase the probability of efficient therapeutic response.

Printed microfluidic filter for heparinized blood.

PubMed

Bilatto, Stanley E R; Adly, Nouran Y; Correa, Daniel S; Wolfrum, Bernhard; Offenhäusser, Andreas; Yakushenko, Alexey

2017-05-01

A simple lab-on-a-chip method for blood plasma separation was developed by combining stereolithographic 3D printing with inkjet printing, creating a completely sealed microfluidic device. In some approaches, one dilutes the blood sample before separation, reducing the concentration of a target analyte and increasing a contamination risk. In this work, a single drop (8  μ l) of heparinized whole blood could be efficiently filtered using a capillary effect without any external driving forces and without dilution. The blood storage in heparin tubes during 24 h at 4 °C initiated the formation of small crystals that formed auto-filtration structures in the sample upon entering the 3D-printed device, with pores smaller than the red blood cells, separating plasma from the cellular content. The total filtration process took less than 10 s. The presented printed plasma filtration microfluidics fabricated with a rapid prototyping approach is a miniaturized, fast and easy-to-operate device that can be integrated into healthcare/portable systems for point-of-care diagnostics.

Compressional and Shear Wakes in a 2D Dusty Plasma Crystal

NASA Astrophysics Data System (ADS)

Nosenko, V.; Goree, J.; Ma, Z. W.; Dubin, D. H. E.

2001-10-01

A 2D crystalline lattice can vibrate with two kinds of sound waves, compressional and shear (transverse), where the latter has a much slower sound speed. When these waves are excited by a moving supersonic disturbance, the superposition of the waves creates a Mach cone, i.e., a V-shaped wake. In our experiments, the supersonic disturbance was a moving spot of argon laser light, and this laser light applied a force, due to radiation pressure, on the particles. The beam was swept across the lattice in a controlled and repeatable manner. The particles were levitated in an argon rf discharge. By moving the laser spot faster than the shear sound speed c_t, but slower than the compressional sound speed c_l, we excited a shear wave Mach cone. Alternatively, by moving the laser spot faster than c_l, we excited both cones. In addition to Mach cones, we also observed a wake structure that arises from the compressional wave’s dispersion. We compare our results to Dubin’s theory (Phys. Plasmas 2000) and to molecular dynamics (MD) simulations.

The use of nicotinic acid to induce sustained low plasma nonesterified fatty acids in feed-restricted Holstein cows.

PubMed

Pires, J A A; Grummer, R R

2007-08-01

The objectives were to determine the effects of nicotinic acid (NA) on blood metabolites (experiment 1) and whether successive doses of NA could induce sustained reductions of plasma nonesterified fatty acids (NEFA; experiment 2) in feed-restricted, nonlactating Holstein cows. Experiment 1 was a single 4 x 4 Latin square with 1-wk periods. Each period consisted of 2.5 d of feed restriction to increase plasma NEFA and 4.5 d of ad libitum feeding. Treatments were abomasal administration of 0, 6, 30, or 60 mg of NA/kg of body weight (BW), given as a single bolus 48 h after initiation of feed restriction. Plasma NEFA concentration decreased from 546 microEq/L to 208 +/- 141 microEq/L at 1 h after the infusion of 6 mg of NA/kg of BW, and to less than 100 +/- 148 microEq/L at 3 h after the abomasal infusion of the 2 highest doses of NA. A rebound occurred after the initial decrease of plasma NEFA concentration. The rebound lasted up to 9 h for the 30-mg dose of NA, and up to 6 h for the 6-mg dose. Experiment 2 was a randomized complete block design with 3 treatments and 6 cows. Starting at 48 h of feed restriction, cows received 9 hourly abomasal infusions of 0, 6, or 10 mg of NA/kg of BW. Plasma NEFA concentrations decreased from 553 microEq/L +/- 24 immediately before the initiation of treatments to <100 microEq/L during hourly infusions of 6 or 10 mg of NA/kg. Data suggest that the maximal antilipolytic response was achieved with the lowest dose of NA. A rebound of NEFA started 2 to 3 h after NA infusions were terminated. In both experiments, the NEFA rebound period coincided with increases in insulin and no change or increased glucose concentrations, suggesting a state of insulin resistance induced by elevated NEFA. This model for reducing plasma NEFA concentration by abomasal infusions of NA can be used to study the metabolic ramifications of elevated vs. reduced NEFA concentrations. The data demonstrate potential benefits and pitfalls of using NA to regulate plasma NEFA and prevent lipid-related metabolic disorders.

Movement of the Melt Metal Layer under Conditions Typical of Transient Events in ITER

NASA Astrophysics Data System (ADS)

Poznyak, I. M.; Safronov, V. M.; Zybenko, V. Yu.

2017-12-01

During the operation of ITER, protective coatings of the divertor and the first wall will be exposed to significant plasma heat loads which may cause a huge erosion. One of the major failure mechanisms of metallic armor is diminution of their thickness due to the melt layer displacement. New experimental data are required in order to develop and validate physical models of the melt layer movement. The paper presents the experiments where metal targets were irradiated by a plasma stream at the quasi-stationary high-current plasma accelerator QSPA-T. The obtained data allow one to determine the velocity and acceleration of the melt layer at various distances from the plasma stream axis. The force causing the radial movement of the melt layer is shown to create an acceleration whose order of magnitude is 1000g. The pressure gradient is not responsible for creating this large acceleration. To investigate the melt layer movement under a known force, the experiment with a rotating target was carried out. The influence of centrifugal and Coriolis forces led to appearance of curved elongated waves on the surface. The surface profile changed: there is no hill in the central part of the erosion crater in contrast to the stationary target. The experimental data clarify the trends in the melt motion that are required for development of theoretical models.

No effect of C-reactive protein on early atherosclerosis development in apolipoprotein E*3-leiden/human C-reactive protein transgenic mice.

PubMed

Trion, A; de Maat, M P M; Jukema, J W; van der Laarse, A; Maas, M C; Offerman, E H; Havekes, L M; Szalai, A J; Princen, H M G; Emeis, J J

2005-08-01

C-reactive protein (CRP) has been associated with risk of cardiovascular disease. It is not clear whether CRP is causally involved in the development of atherosclerosis. Mouse CRP is not expressed at high levels under normal conditions and increases in concentration only several-fold during an acute phase response. Because the dynamic range of human CRP is much larger, apolipoprotein E*3-Leiden (E3L) transgenic mice carrying the human CRP gene offer a unique model to study the role(s) of CRP in atherosclerosis development. Atherosclerosis development was studied in 15 male and 15 female E3L/CRP mice; E3L transgenic littermates were used as controls. The mice were fed a hypercholesterolemic diet to induce atherosclerosis development. Cholesterol exposure did not differ between E3L/CRP and E3L mice. Plasma CRP levels were on average 10.2+/-6.5 mg/L in male E3L/CRP mice, 0.2+/-0.1 mg/L in female E3L/CRP mice, and undetectable in E3L mice. Quantification of atherosclerosis showed that lesion area in E3L/CRP mice was not different from that in E3L mice. This study demonstrates that mildly elevated levels of CRP in plasma do not contribute to the development of early atherosclerosis in hypercholesterolemic E3L/CRP mice.

Fasting plasma total ghrelin concentrations in monozygotic twins discordant for obesity.

PubMed

Leskelä, Piia; Ukkola, Olavi; Vartiainen, Johanna; Rönnemaa, Tapani; Kaprio, Jaakko; Bouchard, Claude; Kesäniemi, Y Antero

2009-02-01

Ghrelin is a hormone that is involved in the regulation of food intake. Neuronal, endocrine, and genetic factors have been shown to regulate plasma ghrelin levels; but the determinants of fasting ghrelin concentrations are not yet fully understood. The main aim was to explore the roles of adiposity and genetic differences in determining fasting plasma total ghrelin levels. We measured total ghrelin levels in a population of 23 monozygotic twin pairs discordant for obesity. In addition, 2 variants of ghrelin gene, namely, Arg51Gln and Leu72Met, were genotyped in 3 populations of monozygotic twin pairs: 23 obesity-discordant, 43 lean-concordant, and 46 obesity-concordant twin pairs. In discordant twins, lean co-twins had higher fasting plasma total ghrelin levels (950 pg/mL, SD = 328 pg/mL) than obese twins (720 pg/mL, SD = 143 pg/mL; P = .003). Arg51Gln-polymorphism of the ghrelin gene was equally distributed between the twin groups. However, there were significant differences in genotype frequencies at the Leu72Met polymorphism between the discordant and obese-concordant groups (P = .003) and between the discordant and lean-concordant groups (P = .011), but not between the 2 concordant groups. In the discordant group, there were fewer Met carriers (4%) than among the obese (17%) or the lean-concordant groups (15%). Plasma total ghrelin levels are affected by acquired obesity independent of genetic background. The Leu72 allele is particularly common among monozygotic twins discordant for obesity, suggesting that this ghrelin allele is more permissive in the regulation of energy balance. The ghrelin gene may thus play a role in the regulation of variability of body weight, such that Leu72 allele carriers are more prone to weight variability in response to environmental factors.

The effects of copper on blood and biochemical parameters of rainbow trout (Oncorhynchus mykiss)

USGS Publications Warehouse

Dethloff, G.M.; Schlenk, D.; Khan, S.; Bailey, H.C.

1999-01-01

Metals are released into aquatic systems from many sources, often at sublethal concentrations. The effects of sublethal concentrations of metals on fish are not entirely understood. The objective of this study was to determine the hematological and biochemical effects of a range of copper concentrations (6.4, 16.0, 26.9 ??g Cu/L) on rainbow trout (Oncorhynchus mykiss) over a prolonged period of time. Trout were exposed to copper, and, at intervals of 3, 7, 14, and 21 days, selected parameters were evaluated. Hemoglobin, hematocrit, plasma glucose, and plasma cortisol levels were elevated in trout exposed to 26.9 ??g Cu/L at day 3 and then returned to levels comparable to control fish. Plasma protein and lactate levels were not significantly altered in trout from any copper treatment. Hepatic copper concentration and hepatic metallothionein mRNA expression were consistently elevated in trout exposed to 26.9 ??g Cu/L. Both of these parameters stabilized by day 3, with only hepatic copper concentration showing a further increase at day 21. Hepatic copper concentration and hepatic metallothionein mRNA expression appear to be robust indicators of copper exposure. Most blood-based parameters evaluated appear to be associated with a transitory, nonspecific stress response. The return of elevated hematological and biochemical parameters to control levels after 3 days and thestabilization of hepatic metallothionein mRNA expression and copper concentration over a similar time period suggested acclimation to dissolved copper at 26.9 ??g/L. Further analysis of the data on blood-based parameters indicated that certain parameters (hemoglobin, hematocrit, plasma glucose, plasma cortisol) may be useful in field monitoring.

RADIATION FROM ELECTRON PHASE SPACE HOLES AS A POSSIBLE SOURCE OF JOVIAN S-BURSTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goodrich, K. A.; Ergun, R. E., E-mail: katherine.goodrich@lasp.colorado.edu

2015-08-10

Radio-frequency short burst emissions (10–40 MHz), known as Jovian S-bursts, have been observed from the Jovian aurora for over fifty years. These emissions, associated with Io’s motion, have a rapidly declining frequency and an exceptionally narrow bandwidth. While it is widely believed that S-bursts are generated by the electron cyclotron maser instability, the mechanism responsible for the rapidly declining frequency and narrow bandwidth currently is not well established. We explore a hypothesis that electron phase space holes radiate or stimulate radiation in the Jovian aurora plasma environment as a possible source of S-burst emissions. Electron phase-space holes (EHs) are ubiquitousmore » in an auroral environment and travel at the implied speeds (∼20,000 km s{sup −1}) of the structures creating the Jovian S-bursts. Furthermore, EHs have the proper physical size to create the observed bandwidth, have sufficient energy content, and can create an environment whereby X mode emissions can be excited. If verified, these findings imply that EHs may be an important source of radiation from strongly magnetized or relativistic astrophysical plasmas.« less

Combination Antiretroviral Treatment for Women Previously Treated Only in Pregnancy: Week 24 Results of AIDS Clinical Trials Group Protocol A5227

PubMed Central

Vogler, Mary A; Smeaton, Laura M; Wright, Rodney L; Cardoso, Sandra Wagner; Sanchez, Jorge; Infante, Rosa; Moran, Laura E; Godfrey, Catherine; Demeter, Lisa M; Johnson, Victoria A

2014-01-01

Background Women with HIV and prior exposure to combination antiretroviral therapy (cART) solely for prevention of Mother to Child Transmission (pMTCT) need to know whether they can later be treated successfully with a commonly used regimen of efavirenz (EFV) and co-formulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) Methods Non-pregnant women with plasma HIV-1 RNA of ≥ 500 copies/mL, previously cART- exposed for pMTCT only, were eligible if they were off ART for ≥ 24 weeks prior to entry, were without evidence of drug resistance on standard genotyping, and were ready to start EFV plus FTC/TDF. The primary endpoint was virologic response (defined as plasma HIV RNA <400 copies/mL) at 24 weeks. Results 54 women were enrolled between 10/07 and 12/09; 52/54 completed 24 weeks of follow- up. Median baseline CD4+ T-cell count was 265/mm3 and baseline plasma HIV-1 RNA was 4.6 log10 copies/mL. Median prior cART duration was 14 weeks, and median time elapsed from the last pMTCT dose to entry was 22 months. Virologic response at 24 weeks was observed in 42/52 women or 81% (exact 95% CI: 68%–90%). There were no differences in response by country, by number or class of prior pMTCT exposures. While confirmed virologic failure occurred in 8 women, no virologic failures were observed in women reporting perfect early adherence. Conclusions In this first prospective clinical trial studying combination antiretroviral re- treatment in women with a history of pregnancy-limited cART, the observed virologic response to TDF/FTC and EFV at 24 weeks was 81%. Virologic failures occurred and correlated with self-reported non-adherence. PMID:24759064

Fasting plasma triglycerides predict the glycaemic response to treatment of Type 2 diabetes by gastric electrical stimulation. A novel lipotoxicity paradigm

PubMed Central

Lebovitz, H E; Ludvik, B; Yaniv, I; Haddad, W; Schwartz, T; Aviv, R

2013-01-01

Background Non-stimulatory, meal-mediated electrical stimulation of the stomach (TANTALUS-DIAMOND) improves glycaemic control and causes modest weight loss in patients with Type 2 diabetes who are inadequately controlled on oral anti-diabetic medications. The magnitude of the glycaemic response in clinical studies has been variable. A preliminary analysis of data from patients who had completed 6 months of treatment indicated that the glycaemic response to the electrical stimulation was inversely related to the baseline fasting plasma triglyceride level. Method An analysis of 40 patients who had had detailed longitudinal studies for 12 months. Results Twenty-two patients with fasting plasma triglycerides ≤ 1.7 mmol/l had mean decreases in HbA1c after 3, 6 and 12 months of gastric contraction modulation treatment of −15 ± 2.1 mmol/mol (−1.39 ± 0.20%), −16 ± 2.2 mmol/mol (−1.48 ± 0.20%) and −14 ± 3.0 mmol/mol (−1.31 ± 0.26%), respectively. In contrast, 18 patients with fasting plasma triglyceride > 1.7 mmol/l had mean decreases in HbA1c of −7 ± 1.7 mmol/mol (−0.66 ± 0.16%), −5 ± 1.6 mmol/mol (−0.44 ± 0.18%) and −5 ± 1.7 mmol/mol (−0.42 ± 0.16%), respectively. Pearson's correlation coefficient between fasting plasma triglyceride and decreases in HbA1c at 12 months of treatment was 0.34 (P < 0.05). Homeostasis model assessment of insulin resistance was unchanged during 12 months of treatment in patients with high baseline fasting triglycerides, while it progressively improved in patients with low fasting plasma triglycerides. Patients with low fasting plasma triglycerides had a tendency to lose more weight than those with high fasting plasma triglycerides, but this did not achieve statistical significance. Conclusions The data presented suggest the existance of a triglyceride lipotoxic mechanism that interferes with gastric/neural mediated pathways that can regulate glycaemic control in patients with type 2 diabetes. The data suggest the existence of a triglyceride lipotoxic pathway that interferes with gastric/neural mediated pathways that can regulate glycaemic control. PMID:23323566

Regulation of Renin Secretion and Arterial Pressure During Prolonged Baroreflex Activation: Influence of Salt Intake

PubMed Central

Hildebrandt, Drew A.; Irwin, Eric D.; Cates, Adam W.; Lohmeier, Thomas E.

2014-01-01

Chronic electrical activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure and is currently being evaluated as antihypertensive therapy for patients with resistant hypertension. However, the influence of variations in salt intake on blood pressure lowering during baroreflex activation has not been determined. As sensitivity of arterial pressure to salt intake is linked to the responsiveness of renin secretion, we determined steady-state levels of arterial pressure and neurohormonal responses in 6 dogs on low, normal, and high salt intakes ( 5, 40, 450 mmol/day, respectively) under control conditions and during a 7-day constant level of baroreflex activation. Under control conditions, there was no difference in mean arterial pressure at low (92±1) and normal (92±2 mmHg) sodium intakes, but pressure increased 9 ±2 mmHg during high salt. Plasma renin activity (2.01±0.23, 0.93±0.20, 0.01±0.01 ng ANGI/mL/hr) and plasma aldosterone (10.3±1.9, 3.5±0.5, 1.7±0.1ng/dL) were inversely related to salt intake, whereas there were no changes in plasma norepinephrine. Although mean arterial pressure (19-22 mmHg) and norepinephrine (20-40%) were lower at all salt intakes during baroreflex activation, neither the changes in pressure nor the absolute values for plasma renin activity or aldosterone in response to salt were different from control conditions. These findings demonstrate that suppression of sympathetic activity by baroreflex activation lowers arterial pressure without increasing renin release and indicate that changes in sympathetic activity are not primary mediators of the effect of salt on renin secretion. Consequently, blood pressure lowering during baroreflex activation is independent of salt intake. PMID:24935941

Membrane-bound guaiacol peroxidases from maize (Zea mays L.) roots are regulated by methyl jasmonate, salicylic acid, and pathogen elicitors

PubMed Central

Mika, Angela; Boenisch, Marike Johanne; Hopff, David; Lüthje, Sabine

2010-01-01

Plant peroxidases are involved in numerous cellular processes in plant development and stress responses. Four plasma membrane-bound peroxidases have been identified and characterized in maize (Zea mays L.) roots. In the present study, maize seedlings were treated with different stresses and signal compounds, and a functional analysis of these membrane-bound class III peroxidases (pmPOX1, pmPOX2a, pmPOX2b, and pmPOX3) was carried out. Total guaiacol peroxidase activities from soluble and microsomal fractions of maize roots were compared and showed weak changes. By contrast, total plasma membrane and washed plasma membrane peroxidase activities, representing peripheral and integral membrane proteins, revealed strong changes after all of the stresses applied. A proteomic approach using 2D-PAGE analysis showed that pmPOX3 was the most abundant class III peroxidase at plasma membranes of control plants, followed by pmPOX2a >pmPOX2b >pmPOX1. The molecular mass (63 kDa) and the isoelectric point (9.5) of the pmPOX2a monomer were identified for the first time. The protein levels of all four enzymes changed in response to multiple stresses. While pmPOX2b was the only membrane peroxidase down-regulated by wounding, all four enzymes were differentially but strongly stimulated by methyl jasmonate, salicylic acid, and elicitors (Fusarium graminearum and Fusarium culmorum extracts, and chitosan) indicating their function in pathogen defence. Oxidative stress applied as H2O2 treatment up-regulated pmPOX2b >pmPOX2a, while pmPOX3 was down-regulated. Treatment with the phosphatase inhibitor chantharidin resulted in distinct responses. PMID:20032108

Antimicrobial Applications of Ambient--Air Plasmas

NASA Astrophysics Data System (ADS)

Pavlovich, Matthew John

The emerging field of plasma biotechology studies the applications of the plasma phase of matter to biological systems. "Ambient-condition" plasmas created at or near room temperature and atmospheric pressure are especially promising for biomedical applications because of their convenience, safety to patients, and compatibility with existing medical technology. Plasmas can be created from many different gases; plasma made from air contains a number of reactive oxygen and nitrogen species, or RONS, involved in various biological processes, including immune activity, signaling, and gene expression. Therefore, ambient-condition air plasma is of particular interest for biological applications. To understand and predict the effects of treating biological systems with ambient-air plasma, it is necessary to characterize and measure the chemical species that these plasmas produce. Understanding both gaseous chemistry and the chemistry in plasma-treated aqueous solution is important because many biological systems exist in aqueous media. Existing literature about ambient-air plasma hypothesizes the critical role of reactive oxygen and nitrogen species; a major aim of this dissertation is to better quantify RONS by produced ambient-air plasma and understand how RONS chemistry changes in response to different plasma processing conditions. Measurements imply that both gaseous and aqueous chemistry are highly sensitive to operating conditions. In particular, chemical species in air treated by plasma exist in either a low-power ozone-dominated mode or a high-power nitrogen oxide-dominated mode, with an unstable transition region at intermediate discharge power and treatment time. Ozone (O3) and nitrogen oxides (NO and NO2, or NOx) are mutually exclusive in this system and that the transition region corresponds to the transition from ozone- to nitrogen oxides-mode. Aqueous chemistry agrees well with to air plasma chemistry, and a similar transition in liquid-phase composition from ozone mode to nitrogen oxides mode occurs as the discharge power increases. One prominent example of plasma biotechnology is the use of plasma-derived reactive species as a novel disinfectant. Ambient-air plasma is an attractive means of disinfection because it is non-thermal, expends a small amount of power, and requires only air and electricity to operate. Both solid surfaces and liquid volumes can be effectively and efficiently decontaminated by the reactive oxygen and nitrogen species that plasma generates. Dry surfaces are decontaminated most effectively by the plasma operating in NOx mode and less effectively in ozone mode, with the weakest antibacterial effects in the transition region, and neutral reactive species are more influential in surface disinfection than charged particles. Aqueous bacterial inactivation correlates well with ozone concentration, suggesting that ozone is the dominant species for bacterial inactivation under the condition of a low-power discharge. Alternatively, air plasma operating in the higher-power, nitrogen oxides-rich mode can create a persistently antibacterial solution. Finally, when near-UV (UVA) treatment follows plasma treatment of bacterial suspension, the antimicrobial effect exceeds the effect predicted from the two treatments alone, and addition of nitrite to aqueous solution, followed by photolysis of nitrite by UVA photons, is hypothesized as the primary mechanism of synergy. The results presented in this dissertation underscore the dynamic nature of air plasma chemistry and the importance of careful chemical characterization of plasma devices intended for biological applications. The complexity of atmospheric pressure plasma devices, and their sensitivity to subtle differences in design and operation, can lead to different results with different mechanisms.

Characterization of glucose-insulin responsiveness and impact of fetal number and sex difference on insulin response in the sheep fetus

PubMed Central

Green, Alice S.; Macko, Antoni R.; Rozance, Paul J.; Yates, Dustin T.; Chen, Xiaochuan; Hay, William W.

2011-01-01

GSIS is often measured in the sheep fetus by a square-wave hyperglycemic clamp, but maximal β-cell responsiveness and effects of fetal number and sex difference have not been fully evaluated. We determined the dose-response curve for GSIS in fetal sheep (0.9 of gestation) by increasing plasma glucose from euglycemia in a stepwise fashion. The glucose-insulin response was best fit by curvilinear third-order polynomial equations for singletons (y = 0.018x3 − 0.26x2 + 1.2x − 0.64) and twins (y = −0.012x3 + 0.043x2 + 0.40x − 0.16). In singles, maximal insulin secretion was achieved at 3.4 ± 0.2 mmol/l glucose but began to plateau after 2.4 ± 0.2 mmol/l glucose (90% of maximum), whereas the maximum for twins was reached at 4.8 ± 0.4 mmol/l glucose. In twin (n = 18) and singleton (n = 49) fetuses, GSIS was determined with a square-wave hyperglycemic clamp >2.4 mmol/l glucose. Twins had a lower basal glucose concentration, and plasma insulin concentrations were 59 (P < 0.01) and 43% (P < 0.05) lower in twins than singletons during the euglycemic and hyperglycemic periods, respectively. The basal glucose/insulin ratio was approximately doubled in twins vs. singles (P < 0.001), indicating greater insulin sensitivity. In a separate cohort of fetuses, twins (n = 8) had lower body weight (P < 0.05) and β-cell mass (P < 0.01) than singleton fetuses (n = 7) as a result of smaller pancreata (P < 0.01) and a positive correlation (P < 0.05) between insulin immunopositive area and fetal weight (P < 0.05). No effects of sex difference on GSIS or β-cell mass were observed. These findings indicate that insulin secretion is less responsive to physiological glucose concentrations in twins, due in part to less β-cell mass. PMID:21343544

Use of reconstructed 3D VMEC equilibria to match effects of toroidally rotating discharges in DIII-D

DOE PAGES

Wingen, Andreas; Wilcox, Robert S.; Cianciosa, Mark R.; ...

2016-10-13

Here, a technique for tokamak equilibrium reconstructions is used for multiple DIII-D discharges, including L-mode and H-mode cases when weakly 3D fieldsmore » $$\\left(\\delta B/B\\sim {{10}^{-3}}\\right)$$ are applied. The technique couples diagnostics to the non-linear, ideal MHD equilibrium solver VMEC, using the V3FIT code, to find the most likely 3D equilibrium based on a suite of measurements. It is demonstrated that V3FIT can be used to find non-linear 3D equilibria that are consistent with experimental measurements of the plasma response to very weak 3D perturbations, as well as with 2D profile measurements. Observations at DIII-D show that plasma rotation larger than 20 krad s –1 changes the relative phase between the applied 3D fields and the measured plasma response. Discharges with low averaged rotation (10 krad s –1) and peaked rotation profiles (40 krad s –1) are reconstructed. Similarities and differences to forward modeled VMEC equilibria, which do not include rotational effects, are shown. Toroidal phase shifts of up to $${{30}^{\\circ}}$$ are found between the measured and forward modeled plasma responses at the highest values of rotation. The plasma response phases of reconstructed equilibra on the other hand match the measured ones. This is the first time V3FIT has been used to reconstruct weakly 3D tokamak equilibria.« less

Evaluation of tranexamic acid and ε-aminocaproic acid concentrations required to inhibit fibrinolysis in plasma of dogs and humans.

PubMed

Fletcher, Daniel J; Blackstock, Kelly J; Epstein, Kira; Brainard, Benjamin M

2014-08-01

To determine minimum plasma concentrations of the antifibrinolytic agents tranexamic acid (TEA) and ε-aminocaproic acid (EACA) needed to completely inhibit fibrinolysis in canine and human plasma after induction of hyperfibrinolysis. Pooled citrated plasma from 7 dogs and commercial pooled citrated human plasma. Concentrations of EACA from 0 μg/mL to 500 μg/mL and of TEA from 0 μg/mL to 160 μg/mL were added to pooled citrated canine and human plasma. Hyperfibrinolysis was induced with 1,000 units of tissue plasminogen activator/mL, and kaolin-activated thromboelastography was performed in duplicate. The minimum concentrations required to completely inhibit fibrinolysis 30 minutes after maximum amplitude of the thromboelastography tracing occurred were determined. Minimum plasma concentrations necessary for complete inhibition of fibrinolysis by EACA and TEA in pooled canine plasma were estimated as 511.7 μg/mL (95% confidence interval [CI], 433.2 to 590.3 μg/mL) and 144.7 μg/mL (95% CI, 125.2 to 164.2 μg/mL), respectively. Concentrations of EACA and TEA necessary for complete inhibition of fibrinolysis in pooled human plasma were estimated as 122.0 μg/mL (95% CI, 106.2 to 137.8 μg/mL) and 14.7 μg/mL (95% CI, 13.7 to 15.6 μg/mL), respectively. Results supported the concept that dogs are hyperfibrinolytic, compared with humans. Higher doses of EACA and TEA may be required to fully inhibit fibrinolysis in dogs.

Plasma generating apparatus for large area plasma processing

DOEpatents

Tsai, C.C.; Gorbatkin, S.M.; Berry, L.A.

1991-07-16

A plasma generating apparatus for plasma processing applications is based on a permanent magnet line-cusp plasma confinement chamber coupled to a compact single-coil microwave waveguide launcher. The device creates an electron cyclotron resonance (ECR) plasma in the launcher and a second ECR plasma is created in the line cusps due to a 0.0875 tesla magnetic field in that region. Additional special magnetic field configuring reduces the magnetic field at the substrate to below 0.001 tesla. The resulting plasma source is capable of producing large-area (20-cm diam), highly uniform (.+-.5%) ion beams with current densities above 5 mA/cm[sup 2]. The source has been used to etch photoresist on 5-inch diam silicon wafers with good uniformity. 3 figures.

Plasma generating apparatus for large area plasma processing

DOEpatents

Tsai, Chin-Chi; Gorbatkin, Steven M.; Berry, Lee A.

1991-01-01

A plasma generating apparatus for plasma processing applications is based on a permanent magnet line-cusp plasma confinement chamber coupled to a compact single-coil microwave waveguide launcher. The device creates an electron cyclotron resonance (ECR) plasma in the launcher and a second ECR plasma is created in the line cusps due to a 0.0875 tesla magnetic field in that region. Additional special magnetic field configuring reduces the magnetic field at the substrate to below 0.001 tesla. The resulting plasma source is capable of producing large-area (20-cm diam), highly uniform (.+-.5%) ion beams with current densities above 5 mA/cm.sup.2. The source has been used to etch photoresist on 5-inch diam silicon wafers with good uniformity.

Hypopituitarism after irradiation in children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wara, W.M.; Richards, G.E.; Grumbach, M.M. Kaplan, S.L.

1977-01-01

Nine children were referred to the University of California Medical Center, San Francisco, for growth evaluation. Each had received conventional radiation doses to the head for tumors not involving the hypothalamus or pituitary, and demonstrated clinical and laboratory evidence of hormonal deficiencies several years after treatment. Six had significant height retardation. Growth hormone deficiency was documented in all by lack of response to provocative insulin, arginine, and/or L-dopa stimulation. ACTH function was evaluated by plasma cortisol response to insulin hypoglycemia in 7; one had a subnormal response. Plasma gonadotropins were measured after lutenizing hormone releasing factor (LRF) in 7 patients;more » only one had an abnormal response for age and stage of sexual maturation. Foresight in treatment planning and careful follow-up of patients receiving irradiation to the head is critical, since hypothalamic-pituitary deficiencies which may occur insidiously over many years, can largely be compensated.« less

Association of genetic variations with pharmacokinetics and lipid-lowering response to atorvastatin in healthy Korean subjects.

PubMed

Woo, Hye In; Kim, Suk Ran; Huh, Wooseong; Ko, Jae-Wook; Lee, Soo-Youn

2017-01-01

Statins are effective agents in the primary and secondary prevention of cardiovascular disease, but treatment response to statins varies among individuals. We analyzed multiple genetic polymorphisms and assessed pharmacokinetic and lipid-lowering responses after atorvastatin 80 mg treatment in healthy Korean individuals. Atorvastatin 80 mg was given to 50 healthy Korean male volunteers. Blood samples were collected to measure plasma atorvastatin and lipid concentrations up to 48 hours after atorvastatin administration. Subjects were genotyped for 1,936 drug metabolism and transporter genetic polymorphisms using the Affymetrix DMET plus array. The pharmacokinetics and lipid-lowering effect of atorvastatin showed remarkable interindividual variation. Three polymorphisms in the SLCO1B1 , SLCO1B3 , and ABCC2 genes were associated with either the maximum concentration (C max ) of atorvastatin or changes in total cholesterol or low-density lipoprotein cholesterol (LDL-C). Minor homozygotes (76.5 ng/mL) of SLCO1B1 c.-910G>A showed higher C max than heterozygotes (34.0 ng/mL) and major homozygotes (33.5 ng/mL, false discovery rate P =0.040). C max and the area under the plasma concentration curve from hour 0 to infinity (AUC ∞ ) were higher in carriers of the SLCO1B1 *17 haplotype that included c.-910G>A than in noncarriers (46.1 vs 32.8 ng/mL for C max ; 221.5 vs 154.2 ng/mL for AUC ∞ ). SLCO1B3 c.334G>T homozygotes (63.0 ng/mL) also showed higher C max than heterozygotes (34.7 ng/mL) and major homozygotes (31.4 ng/mL, FDR P =0.037). A nonsynonymous ABCC2 c.1249G>A was associated with small total cholesterol and LDL-C responses (0.23% and -0.70% for G/A vs -11.9% and -17.4% for G/G). The C max tended to increase according to the increase in the number of minor allele of SLCO1B1 c. -910G>A and SLCO1B3 c.334G>T. Genetic polymorphisms in transporter genes, including SLCO1B1 , SLCO1B3 , and ABCC2 , may influence the pharmacokinetics and lipid-lowering response to atorvastatin administration.

Association of genetic variations with pharmacokinetics and lipid-lowering response to atorvastatin in healthy Korean subjects

PubMed Central

Woo, Hye In; Kim, Suk Ran; Huh, Wooseong; Ko, Jae-Wook; Lee, Soo-Youn

2017-01-01

Background Statins are effective agents in the primary and secondary prevention of cardiovascular disease, but treatment response to statins varies among individuals. We analyzed multiple genetic polymorphisms and assessed pharmacokinetic and lipid-lowering responses after atorvastatin 80 mg treatment in healthy Korean individuals. Methods Atorvastatin 80 mg was given to 50 healthy Korean male volunteers. Blood samples were collected to measure plasma atorvastatin and lipid concentrations up to 48 hours after atorvastatin administration. Subjects were genotyped for 1,936 drug metabolism and transporter genetic polymorphisms using the Affymetrix DMET plus array. Results The pharmacokinetics and lipid-lowering effect of atorvastatin showed remarkable interindividual variation. Three polymorphisms in the SLCO1B1, SLCO1B3, and ABCC2 genes were associated with either the maximum concentration (Cmax) of atorvastatin or changes in total cholesterol or low-density lipoprotein cholesterol (LDL-C). Minor homozygotes (76.5 ng/mL) of SLCO1B1 c.-910G>A showed higher Cmax than heterozygotes (34.0 ng/mL) and major homozygotes (33.5 ng/mL, false discovery rate P=0.040). Cmax and the area under the plasma concentration curve from hour 0 to infinity (AUC∞) were higher in carriers of the SLCO1B1*17 haplotype that included c.-910G>A than in noncarriers (46.1 vs 32.8 ng/mL for Cmax; 221.5 vs 154.2 ng/mL for AUC∞). SLCO1B3 c.334G>T homozygotes (63.0 ng/mL) also showed higher Cmax than heterozygotes (34.7 ng/mL) and major homozygotes (31.4 ng/mL, FDR P=0.037). A nonsynonymous ABCC2 c.1249G>A was associated with small total cholesterol and LDL-C responses (0.23% and −0.70% for G/A vs −11.9% and −17.4% for G/G). The Cmax tended to increase according to the increase in the number of minor allele of SLCO1B1 c. −910G>A and SLCO1B3 c.334G>T. Conclusion Genetic polymorphisms in transporter genes, including SLCO1B1, SLCO1B3, and ABCC2, may influence the pharmacokinetics and lipid-lowering response to atorvastatin administration. PMID:28435225

Duodenal L cell density correlates with features of metabolic syndrome and plasma metabolites.

PubMed

van Baar, Annieke C G; Prodan, Andrei; Wahlgren, Camilla D; Poulsen, Steen S; Knop, Filip K; Groen, Albert K; Bergman, Jacques J; Nieuwdorp, Max; Levin, Evgeni

2018-05-01

Enteroendocrine cells are essential for the regulation of glucose metabolism, but it is unknown whether they are associated with clinical features of metabolic syndrome (MetS) and fasting plasma metabolites. We aimed to identify fasting plasma metabolites that associate with duodenal L cell, K cell and delta cell densities in subjects with MetS with ranging levels of insulin resistance. In this cross-sectional study, we evaluated L, K and delta cell density in duodenal biopsies from treatment-naïve males with MetS using machine-learning methodology. We identified specific clinical biomarkers and plasma metabolites associated with L cell and delta cell density. L cell density was associated with increased plasma metabolite levels including symmetrical dimethylarginine, 3-aminoisobutyric acid, kynurenine and glycine. In turn, these L cell-linked fasting plasma metabolites correlated with clinical features of MetS. Our results indicate a link between duodenal L cells, plasma metabolites and clinical characteristics of MetS. We conclude that duodenal L cells associate with plasma metabolites that have been implicated in human glucose metabolism homeostasis. Disentangling the causal relation between L cells and these metabolites might help to improve the (small intestinal-driven) pathophysiology behind insulin resistance in human obesity. © 2018 The authors.

Plasma l-citrulline concentrations in l-arginine-supplemented healthy dogs.

PubMed

Flynn, K M; Kellihan, H B; Trepanier, L A

2017-08-01

To determine whether oral l-arginine increases plasma [l-citrulline] in dogs. Eleven healthy staff-owned dogs were used in this study. Dogs (n = 3) were given l-arginine (50mg/kg PO q8h) for 7 days, and plasma [l-arginine] and [l-citrulline] were analyzed by high performance liquid chromatography at baseline (BL), steady state trough, and 0.5, 1, 1.5, 2, 4, 6, and 8 h after final dosing on day 7. Eleven dogs were then treated with 100mg/kg l-arginine PO q8h for 7 days, and [l-arginine] and [l-citrulline] were measured at BL, steady state trough, and at peak 4 hrs after dosing (T4 hrs). - Plasma [l-arginine] and [l-citrulline] peaked at T4 hrs on the 50mg/kg dosage. Target outcome, modeled after human study results, of a doubling of [l-arginine] and a 25-30% increase in [l-citrulline] from BL were not reached. After the 100mg/kg dosage, plasma [l-arginine] increased from a BL median of 160.1 μM (range, 100.2-231.4 μM) to a peak of 417.4 μM (206.5-807.3 μM) at T4 hrs, and plasma [l-citrulline] increased from a BL median of 87.8 μM (59.1-117.1 μM) to peak of 102.2 μM (47.4-192.6 μM) at T4 hrs. Ten of eleven dogs showed a doubling of plasma [l-arginine] and 4/11 dogs achieved 25-30% or greater increases in plasma [l-citrulline]. No adverse effects on heart rate or blood pressure were noted. - Oral l-arginine dosage of 100mg/kg q8h doubles plasma [l-arginine] in healthy dogs, but conversion to l-citrulline is quite variable. Further evaluation of this dosage regimen in dogs with pulmonary hypertension is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

The impact of intrarenal nitric oxide synthase inhibition on renal blood flow and function in mild and severe hyperdynamic sepsis.

PubMed

Ishikawa, Ken; Bellomo, Rinaldo; May, Clive N

2011-04-01

In experimental hyperdynamic sepsis, renal function deteriorates despite renal vasodilatation and increased renal blood flow. Because nitric oxide is increased in sepsis and participates in renal blood flow control, we investigated the effects of intrarenal Nω-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase inhibitor, in mild and severe sepsis. Prospective crossover and randomized control interventional studies. University-affiliated research institute. Thirty-two merino ewes. Examination of responses to intrarenal infusion of Nω-nitro-L-arginine methyl ester for 8 hrs in unilaterally nephrectomized normal sheep and in sheep administered Escherichia coli. : In normal sheep, Nω-nitro-L-arginine methyl ester decreased renal blood flow (301 ± 30 to 228 ± 26 mL/min) and creatinine clearance (40.0 ± 5.8 to 31.1 ± 2.8 mL/min), whereas plasma creatinine increased, but fractional excretion of sodium was unchanged. In sheep with nonhypotensive hyperdynamic sepsis, plasma creatinine increased and there were decreases in creatinine clearance (34.5 ± 4.6 to 20.1 ± 3.7 mL/min) and fractional excretion of sodium despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester normalized renal blood flow and increased urine output, but creatinine clearance did not improve and plasma creatinine and fractional excretion of sodium increased. In sheep with severe hypotensive sepsis, creatinine clearance decreased further (31.1 ± 5.4 to 16.0 ± 1.7 mL/min) despite increased renal blood flow. Infusion of Nω-nitro-L-arginine methyl ester restored mean arterial pressure and reduced renal blood flow but did not improve plasma creatinine or creatinine clearance. In hyperdynamic sepsis, with or without hypotension, creatinine clearance decreased despite increasing renal blood flow. Intrarenal Nω-nitro-L-arginine methyl ester infusion reduced renal blood flow but did not improve creatinine clearance. These data indicate that septic acute kidney injury is not the result of decreased renal blood flow nor is it improved by nonspecific nitric oxide synthase inhibition.

Energetic particle-driven compressional Alfvén eigenmodes and prospects for ion cyclotron emission studies in fusion plasmas

NASA Astrophysics Data System (ADS)

Gorelenkov, N. N.

2016-10-01

As a fundamental plasma oscillation the compressional Alfvén waves (CAWs) are interesting for plasma scientists both academically and in applications for fusion plasmas. They are believed to be responsible for the ion cyclotron emission (ICE) observed in many tokamaks. The theory of CAW and ICE was significantly advanced at the end of 20th century in particular motivated by first DT experiments on TFTR and subsequent JET DT experimental studies. More recently, ICE theory was advanced by ST (or spherical torus) experiments with the detailed theoretical and experimental studies of the properties of each instability signal. There the instability responsible for ICE signals previously indistinguishable in high aspect ratio tokamaks became the subjects of experimental studies. We discuss further the prospects of ICE theory and its applications for future burning plasma experiments such as the ITER tokamak-reactor prototype being build in France where neutrons and gamma rays escaping the plasma create extremely challenging conditions for fusion alpha particle diagnostics. This manuscript has been authored by Princeton University under Contract Number DE-AC02-09CH11466 with the US Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes.

Effects of plane of nutrition and feed deprivation on insulin responses in dairy cattle during late gestation.

PubMed

Schoenberg, K M; Ehrhardt, R M; Overton, T R

2012-02-01

Nonlactating Holstein cows (n=12) in late pregnancy were used to determine effects of plane of nutrition followed by feed deprivation on metabolic responses to insulin. Beginning 48 d before expected parturition, cows were fed to either a high plane (HP) or a low plane (LP) of nutrition (162 and 90% of calculated energy requirements, respectively). Cows were subjected to an intravenous glucose tolerance test [GTT; 0.25 g of dextrose/kg of body weight (BW)] on d 14 of treatment and a hyperinsulinemic-euglycemic clamp (HEC; 1 μg/kg of BW/h) on d 15. Following 24 h of feed removal, cows were subjected to a second GTT on d 17 and a second HEC on d 18 after 48 h of feed removal. During the feeding period, plasma nonesterified fatty acid (NEFA) concentrations were higher for cows fed the LP diet compared with those fed the HP diet (163.6 vs. 73.1 μEq/L), whereas plasma insulin was higher for cows fed the HP diet during the feeding period (11.1 vs. 5.2 μIU/mL). Glucose areas under the curve during both GTT were higher for cows fed the LP diet than for those fed the HP diet (4,213 vs. 3,750 mg/dL × 60 min) and was higher during the GTT in the feed-deprived state (4,878 vs. 3,085 mg/dL × 60 min) than in the GTT during the fed state, suggesting slower clearance of glucose during negative energy balance either pre-or post-feed deprivation. This corresponded with a higher dextrose infusion rate during the fed-state HEC than during the feed-deprived-state HEC (203.3 vs. 90.1 mL/h). Plasma NEFA decreased at a faster rate following GTT during feed deprivation compared with that during the fed state (8.7 vs. 2.9%/min). Suppression of NEFA was highest for cows fed the HP diet during the GTT conducted during feed deprivation, and lowest for cows fed the HP diet during the fed-state GTT (68.6 vs. 50.3% decrease from basal). Plasma insulin responses to GTT were affected by feed deprivation such that cows had a much lower insulin response to GTT by 24 h after feed removal (995 vs. 3,957 μIU/mL × 60 min). During the fed-state HEC, circulating concentrations of NEFA were 21% below basal for cows fed the HP diet and 62% below basal for cows fed the LP diet; during feed deprivation, NEFA were 79 and 59% below basal for the HP and LP diets, respectively (diet × HEC). Cows that are fed below energy requirements or are feed deprived have slower clearance of glucose and greater NEFA responses to glucose challenge. Additionally, feed deprivation had a large effect on insulin secretion. Overall, effects of feed deprivation were larger than effects of plane of nutrition. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of Almond- and Olive Oil-Based Docosahexaenoic- and Vitamin E-Enriched Beverage Dietary Supplementation on Inflammation Associated to Exercise and Age

PubMed Central

Capó, Xavier; Martorell, Miquel; Sureda, Antoni; Riera, Joan; Drobnic, Franchek; Tur, Josep Antoni; Pons, Antoni

2016-01-01

n-3-polyunsaturated fatty acids and polyphenols are potential key factors for the treatment and prevention of chronic inflammation associated to ageing and non-communicable diseases. The aim was to analyse effects of an almond and olive oil beverage enriched with α-tocopherol and docosahexaenoic, exercise and age on inflammatory plasma markers, and immune gene expression in peripheral blood mononuclear cells (PBMCs). Five young and five senior athletes who were supplemented for five weeks with a functional beverage performed a stress test under controlled conditions before and after beverage supplementation. Blood samples were taken immediately before and 1 h after each test. Plasma, erythrocytes and PBMCs were isolated. Beverage supplementation increased plasmatic Tumour Necrosis Factor α (TNFα) levels depending on age and exercise. Exercise increased plasma non esterified fatty acids (NEFAs), soluble Intercellular adhesion molecule 3 (sICAM3) and soluble L-selectin (sL-Selectin), and this increase was attenuated by the supplementation. Exercise increased PGE2 plasma levels in supplemented young and in senior placebo athletes. Exercise increased NFkβ-activated levels in PBMCs, which are primed to a pro-inflammatory response increasing pro-inflammatory genes expression after the exercise mainly in the young group after the supplementation. The functional beverage supplementation to young athletes enhances a pro-inflammatory circulating environment in response to the exercise that was less evident in the senior group. PMID:27735833

Effects of Almond- and Olive Oil-Based Docosahexaenoic- and Vitamin E-Enriched Beverage Dietary Supplementation on Inflammation Associated to Exercise and Age.

PubMed

Capó, Xavier; Martorell, Miquel; Sureda, Antoni; Riera, Joan; Drobnic, Franchek; Tur, Josep Antoni; Pons, Antoni

2016-10-09

n -3-polyunsaturated fatty acids and polyphenols are potential key factors for the treatment and prevention of chronic inflammation associated to ageing and non-communicable diseases. The aim was to analyse effects of an almond and olive oil beverage enriched with α-tocopherol and docosahexaenoic, exercise and age on inflammatory plasma markers, and immune gene expression in peripheral blood mononuclear cells (PBMCs). Five young and five senior athletes who were supplemented for five weeks with a functional beverage performed a stress test under controlled conditions before and after beverage supplementation. Blood samples were taken immediately before and 1 h after each test. Plasma, erythrocytes and PBMCs were isolated. Beverage supplementation increased plasmatic Tumour Necrosis Factor α (TNFα) levels depending on age and exercise. Exercise increased plasma non esterified fatty acids (NEFAs), soluble Intercellular adhesion molecule 3 (sICAM3) and soluble L-selectin (sL-Selectin), and this increase was attenuated by the supplementation. Exercise increased PGE2 plasma levels in supplemented young and in senior placebo athletes. Exercise increased NFkβ-activated levels in PBMCs, which are primed to a pro-inflammatory response increasing pro-inflammatory genes expression after the exercise mainly in the young group after the supplementation. The functional beverage supplementation to young athletes enhances a pro-inflammatory circulating environment in response to the exercise that was less evident in the senior group.

The Effect of Isomaltulose Together with Green Tea on Glycemic Response and Antioxidant Capacity: A Single-Blind, Crossover Study in Healthy Subjects.

PubMed

Suraphad, Passakorn; Suklaew, Phim On; Ngamukote, Sathaporn; Adisakwattana, Sirichai; Mäkynen, Kittana

2017-05-06

Isomaltulose, a naturally-occurring isomer of sucrose, is commonly used as an alternative sweetener in foods and beverages. The goal of this study was to determine the effect of isomaltulose together with green tea on postprandial plasma glucose and insulin concentration, as well as antioxidant capacity in healthy subjects. In a randomized, single-blind, crossover study, 15 healthy subjects (eight women and seven men; ages 23.5 ± 0.7 years; with body mass index of 22.6 ± 0.4 kg/m²) consumed five beverages: (1) 50 g sucrose in 400 mL water; (2) 50 g isomaltulose in 400 mL of water; (3) 400 mL of green tea; (4) 50 g sucrose in 400 mL of green tea; and (5) 50 g isomaltulose in 400 mL of green tea. Incremental area under postprandial plasma glucose, insulin, ferric reducing ability of plasma (FRAP) and malondialdehyde (MDA) concentration were determined during 120 min of administration. Following the consumption of isomaltulose, the incremental 2-h area under the curve (AUC 0-2 h ) indicated a higher reduction of postprandial glucose (43.4%) and insulin concentration (42.0%) than the consumption of sucrose. The addition of green tea to isomaltulose produced a greater suppression of postprandial plasma glucose (20.9%) and insulin concentration (37.7%). In accordance with antioxidant capacity, consumption of sucrose (40.0%) and isomaltulose (28.7%) caused the reduction of green tea-induced postprandial increases in FRAP. A reduction in postprandial MDA after drinking green tea was attenuated when consumed with sucrose (34.7%) and isomaltulose (17.2%). In conclusion, green tea could enhance the reduction of postprandial glucose and insulin concentration when consumed with isomaltulose. In comparison with sucrose, isomaltulose demonstrated less alteration of plasma antioxidant capacity after being consumed with green tea.

A head to head evaluation of 8 biochemical scanning tools for unmeasured ions.

PubMed

Morgan, Thomas J; Anstey, Chris M; Wolf, Matthew B

2017-04-01

We aimed to evaluate the sensitivity and specificity of 8 biochemical scanning tools in signalling the presence of unmeasured anions. We used blood gas and biochemical data from 15 patients during and after cardio-pulmonary bypass. Sampling time-points were pre-bypass (T1), 2 min post equilibration with priming fluid containing acetate and gluconate anions (T2), late bypass (T3) and 4 h after surgery (T4). We calculated the anion gap (AG), albumin-corrected anion gap (AGc), whole blood base excess (BE) gap, plasma BE gap, standard BE gap and the strong ion gap (SIG), plus 2 new indices-the unmeasured ion index (UIX) and unmeasured plasma anions according to the interstitial, plasma and erythrocyte acid-base model (IPEua). Total measured plasma concentrations of acetate and gluconate [XA] were proxies for unmeasured plasma anions. [XA] values (mmol/L) were 1.41 (0.87) at T1, 11.73 (3.28) at T2, 4.80 (1.49) at T3 and 1.36 (0.73) at T4. Corresponding [albumin] values (g/L) were 32.3 (2.0), 19.8 (2.6), 21.3 (2.5) and 29.1 (2.3) respectively. Only the AG failed to increase significantly at T2 in response to a mean [XA] surge of >10 mEq/L. At an [XA] threshold of 6 mEq/L, areas under receiver -operator characteristic curves in rank order were IPEua and UIX (0.88 and 0.87 respectively), SIG (0.81), AGc (0.79), standard BE gap (0.77), plasma BE gap (0.71), BE gap (0.70) and AG (0.59). Similar ranking hierarchies applied to positive and negative predictive values. We conclude that during acute hemodilution UIX and IPEua are superior to the anion gap (with and without albumin correction) and 4 other indices as scanning tools for unmeasured anions.

Pharmacokinetics of tildipirosin in bovine plasma, lung tissue, and bronchial fluid (from live, nonanesthetized cattle).

PubMed

Menge, M; Rose, M; Bohland, C; Zschiesche, E; Kilp, S; Metz, W; Allan, M; Röpke, R; Nürnberger, M

2012-12-01

The pharmacokinetics of tildipirosin (Zuprevo(®) 180 mg/mL solution for injection for cattle), a novel 16-membered macrolide for treatment, control, and prevention of bovine respiratory disease, were investigated in studies collecting blood plasma, lung tissue, and in vivo samples of bronchial fluid (BF) from cattle. After single subcutaneous (s.c.) injection at 4 mg/kg body weight, maximum plasma concentration (C(max)) was 0.7 μg/mL. T(max) was 23 min. Mean residence time from the time of dosing to the time of last measurable concentration (MRT(last)) and terminal half-life (T(1/2) ) was 6 and 9 days, respectively. A strong dose-response relationship with no significant sex effect was shown for both C(max) and area under the plasma concentration-time curve from time 0 to the last sampling time with a quantifiable drug concentration (AUC(last) ) over the range of doses up to 6 mg/kg. Absolute bioavailability was 78.9%. The volume of distribution based on the terminal phase (V(z)) was 49.4 L/kg, and the plasma clearance was 144 mL/h/kg. The time-concentration profile of tildipirosin in BF and lung far exceeded those in blood plasma. In lung, tildipirosin concentrations reached 9.2 μg/g at 4 h, peaked at 14.8 μg/g at day 1, and slowly declined to 2.0 μg/g at day 28. In BF, the concentration of tildipirosin reached 1.5 and 3.0 μg/g at 4 and 10 h, maintained a plateau of about 3.5 μg/g between day 1 and 3, and slowly declined to 1.0 at day 21. T(1/2) in lung and BF was approximately 10 and 11 days. Tildipirosin is rapidly and extensively distributed to the respiratory tract followed by slow elimination. © 2011 Blackwell Publishing Ltd.

Epidural analgesia in early labour blocks the stress response but uterine contractions remain unchanged.

PubMed

Scull, T J; Hemmings, G T; Carli, F; Weeks, S K; Mazza, L; Zingg, H H

1998-07-01

To determine the effect of epidural analgesia on biochemical markers of stress, plasma oxytocin concentrations and frequency of uterine contractions during the first stage of labour. Nine nulliparous women, in spontaneous labour, with a singleton fetus and cervical dilatation < or = 5 cm were enrolled. Epidural bupivacaine 0.25% (range 10-14 ml) was administered and bilateral sensory blockade to ice (T8-L4) achieved. Blood samples were collected before the epidermal block and every 10 min for one hour after the block was achieved for the measurement of plasma beta-endorphin, cortical, glucose, lactate and oxytocin concentrations. No exogenous oxytocin was given. Intensity of pain was assessed at the time of the blood sampling using a 10 cm visual analogue scale (VAS). The frequency of uterine contractions was recorded for 60 min before and after the epidural block. There was a decrease in plasma beta-endorphin and cortisol concentrations after epidural block (P < 0.01). There were no changes in plasma glucose and lactate concentrations. The mean VAS for pain decreased 10 min after epidural block was achieved and remained < 2 throughout the study period (P < 0.001). Mean plasma oxytocin concentrations did not change. The frequency of uterine contractions before and after the epidural block was similar. The metabolic stress response to the pain of labour was attenuated by epidural analgesia. In contrast, plasma oxytocin concentration and frequency of uterine contractions were unaffected by the attenuation of metabolic stress response.

The response of the ionosphere to the injection of chemically reactive vapors

NASA Technical Reports Server (NTRS)

Bernhardt, P. A.

1976-01-01

As a gas released in the ionosphere expands, it is rapidly cooled. When the vapor becomes sufficiently tenuous, it is reheated by collisions with the ambient atmosphere and its flow is then governed by diffusive expansion. As the injected gas becomes well mixed with the plasma, a hole is created by chemical processes. In the case of diatomic hydrogen release, depression of the electron concentrations is governed by the charge exchange reaction between oxygen ions and hydrogen, producing positive hydroxyl ions. Hydroxyl ions rapidly react with the electron gas to produce excited oxygen and hydrogen atoms. Enhanced airglow emissions result from the transition of the excited atoms to lower energy states. The electron temperature in the depleted region rises sharply causing a thermal expansion of the plasma and a further reduction in the local plasma concentration.

Subsonic and Supersonic shear flows in laser driven high-energy-density plasmas

NASA Astrophysics Data System (ADS)

Harding, E. C.; Drake, R. P.; Gillespie, R. S.; Grosskopf, M. J.; Kuranz, C. C.; Visco, A.; Ditmar, J. R.; Aglitskiy, Y.; Weaver, J. L.; Velikovich, A. L.; Hurricane, O. A.; Hansen, J. F.; Remington, B. A.; Robey, H. F.; Bono, M. J.; Plewa, T.

2009-05-01

Shear flows arise in many high-energy-density (HED) and astrophysical systems, yet few laboratory experiments have been carried out to study their evolution in these extreme environments. Fundamentally, shear flows can initiate mixing via the Kelvin-Helmholtz (KH) instability and may eventually drive a transition to turbulence. We present two dedicated shear flow experiments that created subsonic and supersonic shear layers in HED plasmas. In the subsonic case the Omega laser was used to drive a shock wave along a rippled plastic interface, which subsequently rolled-upped into large KH vortices. In the supersonic shear experiment the Nike laser was used to drive Al plasma across a low-density foam surface also seeded with a ripple. Unlike the subsonic case, detached shocks developed around the ripples in response to the supersonic Al flow.

A comparison of the effects of 2 doses of soy protein or casein on serum lipids, serum lipoproteins, and plasma total homocysteine in hypercholesterolemic subjects.

PubMed

Tonstad, Serena; Smerud, Knut; Høie, Lars

2002-07-01

Studies have shown that soy protein reduces some atherogenic lipid and lipoprotein concentrations, although lipoprotein(a) concentrations may be increased. The dose response of soy protein has not been established; neither has its effect on plasma total homocysteine. Our objective was to evaluate the effect of 2 doses of soy protein on lipid, lipoprotein, and homocysteine concentrations. Four to 24 wk after being instructed to consume a lipid-lowering diet, 130 men and women with LDL-cholesterol concentrations > or = 4 mmol/L were studied during a parallel group trial in which 4 interventions were assigned randomly. Thirty grams isolated soy protein (ISP) and 10 g cotyledon fiber or 50 g ISP and 16.6 g cotyledon fiber or equivalent doses of casein and cellulose were consumed daily as a beverage for 16 wk. When the 2 groups who consumed ISP were compared with the 2 groups who consumed casein, the differences in the net changes from baseline to week 16 in the concentrations of LDL cholesterol and plasma total homocysteine were -0.26 mmol/L (95% CI: -0.43, -0.09 mmol/L; P = 0.01) and -0.8 micromol/L (-1.4, -0.2 micromol/L; P = 0.005), respectively. The effect of the ISP dose was not significant. There were no significant differences between the 2 ISP and the 2 casein groups in changes in lipoprotein(a), HDL-cholesterol, or triacylglycerol concentrations. Adding 30-50 g soy protein/d to a lipid-lowering diet significantly reduced LDL-cholesterol concentrations without increasing lipoprotein(a) concentrations. Plasma total homocysteine concentrations also decreased, suggesting a novel, possibly antiatherosclerotic effect.

Sustained improvements in plasma ACTH and clinical status in a patient with Nelson's syndrome treated with pasireotide LAR, a multireceptor somatostatin analog.

PubMed

Katznelson, Laurence

2013-05-01

Nelson's syndrome refers to aggressive pituitary corticotroph adenoma growth after bilateral adrenalectomy for treatment of Cushing's disease (CD). Pasireotide, a novel somatostatin analog, has been effective in treating CD. Here, the first case report of a patient with Nelson's syndrome treated with pasireotide is presented. A 55-year-old female was diagnosed with CD in 1973 at age 15 years and underwent bilateral adrenalectomy 1 year later. She subsequently developed Nelson's syndrome and underwent multiple surgeries and radiotherapy for adenoma growth. After presentation with ocular pain, third cranial nerve palsy, and a finding of suprasellar tumor enlargement with hemorrhage, she began pasireotide long-acting release 60 mg/28 days im. At baseline, fasting plasma ACTH was 42 710 pg/mL (normal, 5-27 pg/mL), and fasting plasma glucose was 98 mg/dL. After 1 month, ACTH declined to 4272 pg/mL, and it has remained stable over 19 months of follow-up. Hyperpigmentation progressively improved. Magnetic resonance imaging scans show reduction in the suprasellar component. Fasting plasma glucose increased to 124 mg/dL, and the patient underwent diabetes management. In this clinical case seminar, the current understanding of the treatment of Nelson's syndrome and the use of pasireotide in CD are summarized. A case of Nelson's syndrome with clinically significant and dramatic biochemical and clinical responses to pasireotide administration is reported. Hyperglycemia was noted after pasireotide administration. Pasireotide may represent a useful tool in the medical management of Nelson's syndrome. Further study of the potential benefits and risks of pasireotide in this population is necessary.

Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer?

PubMed

George, Rani; Haywood, Alison; Good, Phillip; Hennig, Stefanie; Khan, Sohil; Norris, Ross; Hardy, Janet

2017-09-01

Methadone is a potent analgesic used to treat refractory cancer pain. It is administered as a racemic mixture, with the l-enantiomer being primarily a μ-receptor agonist, whereas the d-enantiomer is an N-methyl-d-aspartate antagonist and inhibits serotonin and norepinephrine reuptake. Dose requirements vary greatly among patients to achieve optimal pain control and to avoid the risk of adverse effects. The relationship between plasma and saliva methadone enantiomer concentrations was investigated to determine if saliva could be a substitute for plasma in pharmacodynamic and pharmacokinetic studies for clinical monitoring and dose optimization of methadone in patients with advanced cancer. Patients with advanced cancer who were prescribed varying doses of oral methadone for pain management were recruited to obtain paired plasma and saliva samples. Pain scores were recorded at the time of sampling. The total and unbound plasma and saliva concentrations of the l- and d-enantiomers of methadone were quantified by using an HPLC-MS/MS method. The relationship between plasma (total and unbound) and saliva concentrations were compared. The saliva-to-plasma concentration ratio was compared versus the dose administered and the time after dosing for both enantiomers. The association of methadone concentrations with reported pain scores was compared by using a Mann-Whitney U test for significance. Fifty patients receiving a mean dose of 11mg/d of methadone provided 151 paired plasma and saliva samples. The median age of the population was 61 years with an interquartile range of 53-71 years with total body weight ranging from 59-88 kg. Median (interquartile) total plasma concentrations for l- and d-methadone were 50.78 ng/mL (30.6-113.0 ng/mL) and 62.0 ng/mL (28.7-116.0 ng/mL), respectively. Median (interquartile range) saliva concentrations for l- and d-methadone were 81.5 ng/mL (28.0-203.2 ng/mL) and 44.2 (16.2-149.7 ng/mL). No relationship could be established between plasma and saliva concentrations for l- and d-methadone (r 2 = 0.35 and 0.25). The saliva-to-plasma concentration analyzed with the methadone dose showed higher saliva concentrations at lower doses. Dose-normalized saliva concentrations followed a similar pattern over time compared with plasma concentrations. No correlation was found between l-methadone plasma, d-methadone plasma, l-methadone saliva, d-methadone saliva concentrations, and pain score. Saliva concentration was not a better predictor of pain control than plasma concentration for dose optimization and monitoring studies of methadone in patients with cancer. Although the saliva-to-plasma ratio of the concentration of methadone enantiomers was stable across the dosing range, due to the variability in individual saliva-to-plasma ratios, saliva sampling may not be a valid substitute in pharmacokinetic studies of methadone in cancer. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Effects of nitrogen seeding on core ion thermal transport in JET ILW L-mode plasmas

NASA Astrophysics Data System (ADS)

Bonanomi, N.; Mantica, P.; Citrin, J.; Giroud, C.; Lerche, E.; Sozzi, C.; Taylor, D.; Tsalas, M.; Van Eester, D.; contributors, JET

2018-02-01

A set of experiments was carried out in JET ILW (Joint European Torus with ITER-Like Wall) L-mode plasmas in order to study the effects of light impurities on core ion thermal transport. N was puffed into some discharges and its profile was measured by active Charge Exchange diagnostics, while ICRH power was deposited on- and off-axis in ({\\hspace{0pt}}3He)-D minority scheme in order to have a scan of local heat flux at constant total power with and without N injection. Experimentally, the ion temperature profiles are more peaked for similar heat fluxes when N is injected in the plasma. Gyro-kinetic simulations using the GENE code indicate that a stabilization of Ion Temperature Gradient driven turbulent transport due to main ion dilution and to changes in Te/Ti and s/q is responsible of the enhanced peaking. The quasi-linear models TGLF and QuaLiKiz are tested against the experimental and the gyro-kinetic results.

Plasma Glucose Levels for Red Drum Sciaenops Ocellatus in a Florida Estuarine Fisheries Reserve

NASA Technical Reports Server (NTRS)

Bourtis, Carla M.; Francis-Floyd, Ruth; Boggs, Ashley S P.; Reyier, Eric A.; Stolen, Eric D.; Yanong, Roy P.; Guillette, Louis J., Jr.

2015-01-01

Despite the significant value of the southeastern United States' red drum (Sciaenops ocellatus) fishery, there is a lack of clinical blood chemistry data. This was the first study to assess plasma glucose values as an indicator of stress response to evaluate variation and the effect of reproductive activity for wild adult red drum in Florida. Red drum (n=126) were collected from NASA's Kennedy Space Center waters during three reproductive periods in 2011. Samples were obtained from the branchial vessels of the gill arch. Plasma glucose levels were significantly different among reproductive periods, with the highest mean values recorded during the spawning period, September- October (38.23 mg / dL +/- 10.0). The glucose range was 17 - 69 mg / dL. Glucose values were lower during all three periods than previous values recorded for cultured or captive red drum studies. This may indicate that fish from this population were under less stress than other populations previously sampled.

Human exposure to Bisphenol A and liver health status: Quantification of urinary and circulating levels by LC-MS/MS.

PubMed

Nicolucci, Carla; Errico, Sonia; Federico, Alessandro; Dallio, Marcello; Loguercio, Carmelina; Diano, Nadia

2017-06-05

A selective and highly sensitive analytical methodology for determination of Bisphenol A in human plasma was developed and validated. The method was based on selective liquid/solid extraction, combined with liquid chromatography-electrospray ionization tandem mass spectrometry in the multiple reaction monitoring mode and negative ionization. The linearity of the detector response was verified in human plasma over the concentration range 0.100-200ngmL -1 . The detection limit was 0.03ngmL -1 and the quantification limit was 0.100ngmL -1 . The analytical features of the proposed in-house validated method were satisfactory: precision was <10% and recoveries were around 84-104%. The matrix effect was studied and compensated using deuterated labeled standard. The applicability of the proposed method was demonstrated analyzing human plasma samples from individuals affected by non-alcoholic fatty liver disease. Bisphenol A was detected above the detection limit in all samples. The data show a persistence of unconjugated Bisphenol A levels in plasma and indicate a chronic Bisphenol A exposure of the target organ, suggesting an association between liver health status and Bisphenol A exposure. The results from our study are valuable for further investigation with large sample size and longitudinal study designs, necessary to confirm the observed association. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute responses of American kestrels to methyl parathion and fenvalerate

USGS Publications Warehouse

Rattner, B.A.; Franson, J.C.

1984-01-01

Physiological and toxicological effects of p.o, methyl parathion (0.375-3.0 mg/kg) or fenvalerate (1000-4000 mg/kg) were examined over a 10 h period in American kestrels (Falco sparverius) maintained in thermoneutral (22?.C) and cold (-5?.C) environments. Methyl parathion was highly toxic (LD50=3.08 mg/kg, 95% confidence limits=2.29-4.l4 mg/kg, producing overt intoxication (abnormal posture, ataxia, paresis), dose-dependent inhibition (26-67%) of brain acetylcholinesterase activity, hyperglycemia, and elevated plasma corticosterone concentration. Transient but pronounced hypothermia was associated with plasma cholinesterase inhibition in excess of 50% (2 h after intubation), although this response was highly variable (plasma ChE inhibition vs. A cloacal temperature, r=-0.60). Fenvalerate, at doses far exceeding those encountered in the environment, caused mild intoxication (irregular head movement) and elevated plasma alanine aminotransferase activity, but did not alter cloacal temperature, plasma activities of CK, U-HBDH, and LDK, or concentrations of corticosterone, glucose, triiodothyronine, and uric acid. Cold exposure intensified methyl parathion toxicity, but did not affect that of fenvalerate. It would thus appear that the organophosphorus insecticide methyl parathion poses far greater hazard than the pyrethroid fenvalerate to raptorial birds.

Sex Differences in Plasma Prolactin Response to Tryptophan in Chronic Fatigue Syndrome Patients With and Without Comorbid Fibromyalgia

PubMed Central

Weaver, Shelley A.; Janal, Malvin N.; Aktan, Nadine; Ottenweller, John E.

2010-01-01

Abstract Background Some think chronic fatigue syndrome (CFS) and fibromyalgia (FM) are variants of the same illness process. This would imply that CFS patients with and without comorbid FM have similar biological underpinnings. To test this, we compared serotonergic-based responses, plasma prolactin (PRL), and self-reported measures of fatigue to intravenous infusion of tryptophan among patients with CFS alone, CFS + FM, and healthy controls. Methods Men and women with CFS alone or CFS + FM and healthy subjects, none with current major depressive disorder (MDD), were given 120 mg of l-tryptophan per kg lean body mass intravenously (i.v.). Before and after tryptophan infusion, blood samples were collected, and plasma PRL, tryptophan, and kynurenine concentrations were determined. Results Women with CFS alone, but not CFS + FM, showed upregulated plasma PRL responses compared with controls. There were no differences among groups of men. Plasma tryptophan and kynurenine concentrations did not differ among groups. Conclusions These results indicate that women with CFS alone have upregulated serotonergic tone that is not seen in those with comorbid FM. The lack of effect in men suggests a mechanism that might explain, in part, the increased prevalence of CFS in women. The data support the interpretation that CFS in women is a different illness from FM. PMID:20384451

Oscillating plasma bubble and its associated nonlinear studies in presence of low magnetic field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Megalingam, Mariammal; Sarma, Bornali; Mitra, Vramori

Oscillating plasma bubbles have been created around a cylindrical mesh grid of 75% optical transparency in a DC plasma system with a low magnetic field. Plasma bubbles are created by developing ion density gradient around a cylindrical grid of 20 cm in diameter and 25 cm in height, inserted into the plasma. Relaxation and contraction of the plasma bubbles in the presence of external conditions, such as magnetic field and pressure, have been studied. A Langmuir probe has been used to detect the plasma floating potential fluctuations at different imposed experimental conditions. Nonlinear behavior of the system has been characterized by adoptingmore » nonlinear techniques such as Fast Fourier Transform, Phase Space Plot, and Recurrence Plot. It shows that the system creates highly nonlinear phenomena associated with the plasma bubble under the imposed experimental conditions. A theoretical and numerical model has also been developed to satisfy the observed experimental analysis. Moreover, observations are extended further to study the growth of instability associated with the plasma bubbles. The intention of the present work is to correlate the findings about plasma bubbles and their related instability with the one existing in the equatorial F-region of the ionosphere.« less

Cyanex based uranyl sensitive polymeric membrane electrodes.

PubMed

Badr, Ibrahim H A; Zidan, W I; Akl, Z F

2014-01-01

Novel uranyl selective polymeric membrane electrodes were prepared using three different low-cost and commercially available Cyanex extractants namely, bis(2,4,4-trimethylpentyl) phosphinic acid [L1], bis(2,4,4-trimethylpentyl) monothiophosphinic acid [L2] and bis(2,4,4-trimethylpentyl) dithiophosphinic acid [L3]. Optimization and performance characteristics of the developed Cyanex based polymer membrane electrodes were determined. The influence of membrane composition (e.g., amount and type of ionic sites, as well as type of plasticizer) on potentiometric responses of the prepared membrane electrodes was studied. Optimized Cyanex-based membrane electrodes exhibited Nernstian responses for UO₂(2+) ion over wide concentration ranges with fast response times. The optimized membrane electrodes based on L1, L2 and L3 exhibited Nernstian responses towards uranyl ion with slopes of 29.4, 28.0 and 29.3 mV decade(-1), respectively. The optimized membrane electrodes based on L1-L3 showed detection limits of 8.3 × 10(-5), 3.0 × 10(-5) and 3.3 × 10(-6) mol L(-1), respectively. The selectivity studies showed that the optimized membrane electrodes exhibited high selectivity towards UO₂(2+) ion over large number of other cations. Membrane electrodes based on L3 exhibited superior potentiometric response characteristics compared to those based on L1 and L2 (e.g., widest linear range and lowest detection limit). The analytical utility of uranyl membrane electrodes formulated with Cyanex extractant L3 was demonstrated by the analysis of uranyl ion in different real samples for nuclear safeguards verification purposes. The results obtained using direct potentiometry and flow-injection methods were compared with those measured using the standard UV-visible and inductively coupled plasma spectroscopic methods. © 2013 Published by Elsevier B.V.

Sterilization of Surfaces with a Handheld Atmospheric Pressure Plasma

NASA Astrophysics Data System (ADS)

Hicks, Robert; Habib, Sara; Chan, Wai; Gonzalez, Eleazar; Tijerina, A.; Sloan, Mark

2009-10-01

Low temperature, atmospheric pressure plasmas have shown great promise for decontaminating the surfaces of materials and equipment. In this study, an atmospheric pressure, oxygen and argon plasma was investigated for the destruction of viruses, bacteria, and spores. The plasma was operated at an argon flow rate of 30 L/min, an oxygen flow rate of 20 mL/min, a power density of 101.0 W/cm^3 (beam area = 5.1 cm^2), and at a distance from the surface of 7.1 mm. An average 6log10 reduction of viable spores was obtained after only 45 seconds of exposure to the reactive gas. By contrast, it takes more than 35 minutes at 121^oC to sterilize anthrax in an autoclave. The plasma properties were investigated by numerical modeling and chemical titration with nitric oxide. The numerical model included a detailed reaction mechanism for the discharge as well as for the afterglow. It was predicted that at a delivered power density of 29.3 W/cm^3, 30 L/min argon, and 0.01 volume% O2, the plasma generated 1.9 x 10^14 cm-3 O atoms, 1.6 x 10^12 cm-3 ozone, 9.3 x 10^13 cm-3 O2(^1δg), and 2.9 x 10^12 cm-3 O2(^1σ^+g) at 1 cm downstream of the source. The O atom density measured by chemical titration with NO was 6.0 x 10^14 cm-3 at the same conditions. It is believe that the oxygen atoms and the O2(^1δg) metastables were responsible for killing the anthrax and other microorganisms.

Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study

PubMed Central

Katzenschlager, R; Evans, A; Manson, A; Patsalos, P; Ratnaraj, N; Watt, H; Timmermann, L; Van der Giessen, R; Lees, A

2004-01-01

Background: The seed powder of the leguminous plant, Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for diseases including parkinsonism. We have assessed the clinical effects and levodopa (L-dopa) pharmacokinetics following two different doses of mucuna preparation and compared them with standard L-dopa/carbidopa (LD/CD). Methods: Eight Parkinson's disease patients with a short duration L-dopa response and on period dyskinesias completed a randomised, controlled, double blind crossover trial. Patients were challenged with single doses of 200/50 mg LD/CD, and 15 and 30 g of mucuna preparation in randomised order at weekly intervals. L-Dopa pharmacokinetics were determined, and Unified Parkinson's Disease Rating Scale and tapping speed were obtained at baseline and repeatedly during the 4 h following drug ingestion. Dyskinesias were assessed using modified AIMS and Goetz scales. Results: Compared with standard LD/CD, the 30 g mucuna preparation led to a considerably faster onset of effect (34.6 v 68.5 min; p = 0.021), reflected in shorter latencies to peak L-dopa plasma concentrations. Mean on time was 21.9% (37 min) longer with 30 g mucuna than with LD/CD (p = 0.021); peak L-dopa plasma concentrations were 110% higher and the area under the plasma concentration v time curve (area under curve) was 165.3% larger (p = 0.012). No significant differences in dyskinesias or tolerability occurred. Conclusions: The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted. PMID:15548480

Temporal trends of perfluoroalkyl acids in plasma samples of pregnant women in Hokkaido, Japan, 2003-2011.

PubMed

Okada, Emiko; Kashino, Ikuko; Matsuura, Hideyuki; Sasaki, Seiko; Miyashita, Chihiro; Yamamoto, Jun; Ikeno, Tamiko; Ito, Yoichi M; Matsumura, Toru; Tamakoshi, Akiko; Kishi, Reiko

2013-10-01

Perfluoroalkyl acids (PFAAs) are persistent organic pollutants that are used in a wide range of consumer products. Recent epidemiological studies have shown that prenatal exposure to toxic levels of PFAAs in the environment may adversely affect fetal growth and humoral immune response in infants and children. Here we have characterized levels of prenatal exposure to PFAA between 2003 and 2011 in Hokkaido, Japan, by measuring PFAA concentrations in plasma samples from pregnant women. The study population comprised 150 women who enrolled in a prospective birth cohort study conducted in Hokkaido. Eleven PFAAs were measured in maternal plasma samples using simultaneous analysis by ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry. At the end of the study, in 2011, age- and parity-adjusted mean concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorotridecanoic acid (PFTrDA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) were 1.35ng/mL, 1.26ng/mL, 0.66ng/mL, 1.29ng/mL, 0.25ng/mL, 0.33ng/mL, 0.28ng/mL, and 3.86ng/mL, respectively. Whereas PFOS and PFOA concentrations declined 8.4%/y and 3.1%/y, respectively, PFNA and PFDA levels increased 4.7%/y and 2.4%/y, respectively, between 2003 and 2011. PFUnDA, PFDoDA, and PFTrDA were detected in the vast majority of maternal samples, but no significant temporal trend was apparent. Future studies must involve a larger population of pregnant women and their children to determine the effects of prenatal exposure to PFAA on health outcomes in infants and children. © 2013.

A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction.

PubMed

Paine, Mary F; Widmer, Wilbur W; Hart, Heather L; Pusek, Susan N; Beavers, Kimberly L; Criss, Anne B; Brown, Sherri S; Thomas, Brian F; Watkins, Paul B

2006-05-01

Grapefruit juice (GFJ) enhances the systemic exposure of numerous CYP3A4 drug substrates, including felodipine, by inhibiting intestinal (but not hepatic) first-pass metabolism. Furanocoumarins have been identified as major CYP3A4 inhibitors contained in the juice, but their contribution to the GFJ effect in vivo remains unclear. To ascertain whether furanocoumarins mediate the GFJ-felodipine interaction, a furanocoumarin-free GFJ was created and tested against orange juice and the original GFJ with respect to the oral pharmacokinetics of felodipine. With the use of food-grade solvents and absorption resins, furanocoumarins were removed (approximately 99%) from whole GFJ, whereas other major ingredients (flavonoids) were retained. In an open, 3-way, randomized crossover design, 18 healthy volunteers ingested felodipine (10 mg) with 1 of the 3 juices (240 mL). Blood was collected over 24 h. At least 1 wk elapsed between juice treatments. The median and range of the area under the curve and the maximum concentration of felodipine were significantly (P < 0.001) greater with consumption of GFJ [110 (range: 58-270) nmol . h/L and 21 (7.6-50) nmol/L, respectively] than with that of orange juice [54 (29-150) nmol . h/L and 7.6 (3.4-13.9) nmol/L, respectively] or furanocoumarin-free GFJ [48 (23-120) nmol . h/L and 8.3 (3.0-16.6) nmol/L, respectively]. GFJ, orange juice, and furanocoumarin-free GFJ did not differ significantly (P > 0.09) in median time to reach maximum plasma concentration [2.5 (1.5-6), 2.8 (1.5-4), and 2.5 (2-6) h, respectively] or terminal half-life [6.6 (4.2-13.6), 7.8 (4.4-13.2), and 6.8 (2.6-14.4) h, respectively]. Furanocoumarins are the active ingredients in GFJ responsible for enhancing the systemic exposure of felodipine and probably other CYP3A4 substrates that undergo extensive intestinal first-pass metabolism.

NRL Plasma Formulary 2009

DTIC Science & Technology

2009-01-01

Knudsen Kn λ/L Hydrodynamic time / collision time Lewis Le κ/D *Thermal conduction/molecular diffusion Lorentz Lo V/c Magnitude of relativistic effects...to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data...44 Relativistic Electron Beams . . . . . . . . . . . . . . . . . . . . 46 Beam Instabilities

Ad libitum fluid intake and plasma responses after pickle juice, hypertonic saline, or deionized water ingestion.

PubMed

Allen, Scott; Miller, Kevin C; Albrecht, Jay; Garden-Robinson, Julie; Blodgett-Salafia, Elizabeth

2013-01-01

Adding sodium (Na(+)) to drinks improves rehydration and ad libitum fluid consumption. Clinicians (∼25%) use pickle juice (PJ) to treat cramping. Scientists warn against PJ ingestion, fearing it will cause rapid plasma volume restoration and thereby decrease thirst and delay rehydration. Advice about drinking PJ has been developed but never tested. To determine if drinking small volumes of PJ, hypertonic saline (HS), or deionized water (DIW) affects ad libitum DIW ingestion, plasma variables, or perceptual indicators. Crossover study. Laboratory. Fifteen, euhydrated (urine specific gravity ≤ 1.01) men (age = 22 ± 2 years, height = 178 ± 6 cm, mass = 82.9 ± 8.4 kg). Participants completed 3 testing days (≥ 72 hours between days). After a 30-minute rest, a blood sample was collected. Participants completed 60 minutes of hard exercise (temperature = 36 ± 2°C, relative humidity = 16 ± 1%). Postexercise, they rested for 30 minutes; had a blood sample collected; rated thirst, fullness, and nausea; and ingested 83 ± 8 mL of PJ, HS, or DIW. They rated drink palatability (100-mm visual analog scale) and were allowed to drink DIW ad libitum for 60 minutes. Blood samples and thirst, fullness, and nausea ratings (100-mm visual analog scales) were collected at 15, 30, 45, and 60 minutes posttreatment drink ingestion. Ad libitum DIW volume, percentage change in plasma volume, plasma osmolality (OSMp,) plasma sodium concentration ([Na(+)]p), and thirst, fullness, nausea, and palatability ratings. Participants consumed more DIW ad libitum after HS (708.03 ± 371.03 mL) than after DIW (532.99 ± 337.14 mL, P < .05). Ad libitum DIW ingested after PJ (700.35 ± 366.15 mL) was similar to that after HS and DIW (P > .05). Plasma sodium concentration, OSMp, percentage change in plasma volume, thirst, fullness, and nausea did not differ among treatment drinks over time (P > .05). Deionized water (73 ± 14 mm) was more palatable than HS (17 ± 13 mm) or PJ (26 ± 16 mm, P < .05). The rationale behind advice about drinking PJ is questionable. Participants drank more, not less, after PJ ingestion, and plasma variables and perceptual indicators were similar after PJ and DIW ingestion. Pickle juice did not inhibit short-term rehydration.

Two main metabolites of gentiopicroside detected in rat plasma by LC-TOF-MS following 2,4-dinitrophenylhydrazine derivatization.

PubMed

Wang, Zhigang; Tang, Shuhan; Jin, Yan; Zhang, Yan; Hattori, Masao; Zhang, Hailong; Zhang, Ning

2015-03-25

The metabolism of gentiopicroside in vivo was studied by LC/MS following 2,4-dinitrophenylhydrazine derivatization for the first time. The ionization efficiency of the major metabolites erythrocentaurin and gentiopicral were greatly enhanced by the new analytical method developed, and they were successfully detected in rat plasma after oral administration of gentiopicroside. Methyl 4-formylbenzoate was used as the internal standard to quantify erythrocentaurin and gentiopicral in rat plasma in negative mode by UPLC-TOF-MS. It was found that erythrocentaurin reached the maximum plasma concentration of 625.2±246.3 ng/mL at about 2 h and gentiopicral reached the maximum plasma concentration of 157.6±86.6 ng/mL at about 4 h after oral administration of gentiopicroside at a dose of 200 mg/kg. The metabolic pathway of gentiopicroside to erythrocentaurin and gentiopicral was proposed. The monoterpene compound gentiopicroside was found to be metabolized to dihydroisocoumarin in vivo which may be responsible for the pharmacological effect of gentiopicroside. The results may shed light on clinical efficacy of gentiopicroside and the new analytical method developed may assist in studies for the metabolism of other natural iridoids and secoiridoids in vivo. Copyright © 2015 Elsevier B.V. All rights reserved.

Contamination of the Norepinephrine Prodrug Droxidopa by Dihydroxyphenylacetaldehyde

PubMed Central

Holmes, Courtney; Whittaker, Noel; Heredia-Moya, Jorge; Goldstein, David S.

2015-01-01

BACKGROUND l-Threo-3,4-dihydroxyphenylserine (L-DOPS, droxidopa) is a norepinephrine (NE) prodrug under development to treat orthostatic hypotension. 3,4-Dihydroxyphenylacetaldehyde (DOPAL), an endogenous catecholaldehyde produced by enzymatic oxidative deamination of dopamine, is toxic to catecholaminergic neurons. Based on the observation of increasing plasma DOPAL after oral administration of L-DOPS to a patient, we examined whether other subjects also had DOPAL in their plasma after droxidopa administration, and whether droxidopa is contaminated with DOPAL. METHODS Thirteen subjects took 400 mg droxidopa orally. We sampled venous blood at baseline and 1, 2, 3, 6, 24, and 48 h after drug administration and assayed L-DOPS, NE, and DOPAL by use of liquid chromatography with electrochemical detection (LC-ED). Droxidopa in acidic solution (20:80 mixture of 0.04 mol/L phosphoric acid:0.20 mol/L acetic acid) was vacuum centrifuged for 1 h at 30 °C and then assayed by LC-ED. RESULTS Droxidopa contained 0.01% DOPAL. At 6 h after droxidopa, all subjects had detectable DOPAL in plasma (1.89 nmol/L, P = 0.0001). Across the sampling times, plasma DOPAL correlated with plasma L-DOPS (r = 0.996). The mean increment in plasma DOPAL was more than 4 times that in plasma NE (0.39 nmol/L). In 2 patients with Parkinson disease and orthostatic hypotension, DOPAL was detected in plasma at baseline (0.12 nmol/L) and increased by about 70-fold after droxidopa. Vacuum concentration of droxidopa in the acid solution converted L-DOPS to DOPAL completely. CONCLUSIONS Droxidopa is contaminated with DOPAL. After oral droxidopa administration, DOPAL is detected in plasma of humans. Droxidopa is susceptible to extensive nonenzymatic conversion to DOPAL. PMID:20207766

Contamination of the norepinephrine prodrug droxidopa by dihydroxyphenylacetaldehyde.

PubMed

Holmes, Courtney; Whittaker, Noel; Heredia-Moya, Jorge; Goldstein, David S

2010-05-01

L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxidopa) is a norepinephrine (NE) prodrug under development to treat orthostatic hypotension. 3,4-Dihydroxyphenylacetaldehyde (DOPAL), an endogenous catecholaldehyde produced by enzymatic oxidative deamination of dopamine, is toxic to catecholaminergic neurons. Based on the observation of increasing plasma DOPAL after oral administration of L-DOPS to a patient, we examined whether other subjects also had DOPAL in their plasma after droxidopa administration, and whether droxidopa is contaminated with DOPAL. Thirteen subjects took 400 mg droxidopa orally. We sampled venous blood at baseline and 1, 2, 3, 6, 24, and 48 h after drug administration and assayed L-DOPS, NE, and DOPAL by use of liquid chromatography with electrochemical detection (LC-ED). Droxidopa in acidic solution (20:80 mixture of 0.04 mol/L phosphoric acid:0.20 mol/L acetic acid) was vacuum centrifuged for 1 h at 30 degrees C and then assayed by LC-ED. Droxidopa contained 0.01% DOPAL. At 6 h after droxidopa, all subjects had detectable DOPAL in plasma (1.89 nmol/L, P = 0.0001). Across the sampling times, plasma DOPAL correlated with plasma L-DOPS (r = 0.996). The mean increment in plasma DOPAL was more than 4 times that in plasma NE (0.39 nmol/L). In 2 patients with Parkinson disease and orthostatic hypotension, DOPAL was detected in plasma at baseline (0.12 nmol/L) and increased by about 70-fold after droxidopa. Vacuum concentration of droxidopa in the acid solution converted L-DOPS to DOPAL completely. Droxidopa is contaminated with DOPAL. After oral droxidopa administration, DOPAL is detected in plasma of humans. Droxidopa is susceptible to extensive nonenzymatic conversion to DOPAL.

Demonstration of a positron beam-driven hollow channel plasma wakefield accelerator

DOE PAGES

Gessner, Spencer; Adli, Erik; Allen, James M.; ...

2016-06-02

Plasma wakefield accelerators have been used to accelerate electron and positron particle beams with gradients that are orders of magnitude larger than those achieved in conventional accelerators. In addition to being accelerated by the plasma wakefield, the beam particles also experience strong transverse forces that may disrupt the beam quality. Hollow plasma channels have been proposed as a technique for generating accelerating fields without transverse forces. In this study, we demonstrate a method for creating an extended hollow plasma channel and measure the wakefields created by an ultrarelativistic positron beam as it propagates through the channel. The plasma channel ismore » created by directing a high-intensity laser pulse with a spatially modulated profile into lithium vapour, which results in an annular region of ionization. A peak decelerating field of 230 MeV m -1 is inferred from changes in the beam energy spectrum, in good agreement with theory and particle-in-cell simulations.« less

Methods for detecting and correcting inaccurate results in inductively coupled plasma-atomic emission spectrometry

DOEpatents

Chan, George C. Y. [Bloomington, IN; Hieftje, Gary M [Bloomington, IN

2010-08-03

A method for detecting and correcting inaccurate results in inductively coupled plasma-atomic emission spectrometry (ICP-AES). ICP-AES analysis is performed across a plurality of selected locations in the plasma on an unknown sample, collecting the light intensity at one or more selected wavelengths of one or more sought-for analytes, creating a first dataset. The first dataset is then calibrated with a calibration dataset creating a calibrated first dataset curve. If the calibrated first dataset curve has a variability along the location within the plasma for a selected wavelength, errors are present. Plasma-related errors are then corrected by diluting the unknown sample and performing the same ICP-AES analysis on the diluted unknown sample creating a calibrated second dataset curve (accounting for the dilution) for the one or more sought-for analytes. The cross-over point of the calibrated dataset curves yields the corrected value (free from plasma related errors) for each sought-for analyte.

Mechanism for the increase in plasma triacylglycerol concentrations after consumption of short-term, high-carbohydrate diets.

PubMed

Mittendorfer, B; Sidossis, L S

2001-05-01

High-carbohydrate (HC) diets are recommended for lowering the risk of coronary heart disease because they decrease plasma LDL-cholesterol concentrations. However, an unfavorable effect of HC diets is an increase in plasma triacylglycerol concentrations. The underlying mechanisms of this effect are still unclear. We examined the effect of diet composition on VLDL-triacylglycerol metabolism using in vivo isotopically labeled VLDL-triacylglycerol tracers. Six healthy subjects were studied on 2 occasions: after 2 wk of an HC diet (75% carbohydrates, 10% fat, and 15% protein) and after 2 wk of an isoenergetic high-fat (HF) diet (30% carbohydrates, 55% fat, and 15% protein). The plasma VLDL-triacylglycerol concentration was higher after the HC diet than after the HF diet (690 +/- 186 compared with 287 +/- 104 micromol/L; P < 0.05) because of higher rates of VLDL-triacylglycerol production (0.76 +/- 0.12 compared with 0.45 +/- 0.15 micromol x kg(-1) x min(-1); P < 0.05) rather than diminished VLDL-triacylglycerol clearance (1.5 +/- 0.5 compared with 1.7 +/- 0.5 mL x kg(-1) x min(-1) after the HC diet than after the HF diet, respectively). The increase in VLDL-triacylglycerol production was probably mediated by a decrease in hepatic fatty acid oxidation after the HC diet (0.13 +/- 0.02 compared with 0.69 +/- 0.24 micromol x kg(-1) x min(-1); P < 0.05), which presumably increased hepatic fatty acid availability for triacylglycerol synthesis. The increase in fasting plasma triacylglycerol concentrations in response to short-term HC diets is due to accelerated VLDL-triacylglycerol secretion. Increased hepatic fatty acid availability, resulting from reduced hepatic fatty acid oxidation, is most likely responsible for the observed increase in VLDL-triacylglycerol secretion.

Norepinephrine precursor therapy in neurogenic orthostatic hypotension.

PubMed

Kaufmann, Horacio; Saadia, Daniela; Voustianiouk, Andrei; Goldstein, David S; Holmes, Courtney; Yahr, Melvin D; Nardin, Rachel; Freeman, Roy

2003-08-12

In patients with neurogenic orthostatic hypotension (NOH), the availability of the sympathetic neurotransmitter norepinephrine (NE) in the synaptic cleft is insufficient to maintain blood pressure while in the standing posture. We determined the effect of oral administration of the synthetic amino acid L-threo-3,4-dihydroxyphenylserine (L-DOPS), which is decarboxylated to NE by the enzyme L-aromatic amino acid decarboxylase (L-AADC) in neural and nonneural tissue, on blood pressure and orthostatic tolerance in 19 patients with severe NOH (8 with pure autonomic failure and 11 with multiple-system atrophy). A single-blind dose-titration study determined the most appropriate dose for each patient. Patients were then enrolled in a double-blind, placebo-controlled, crossover trial. L-DOPS significantly raised mean blood pressure both supine (from 101+/-4 to 141+/-5 mm Hg) and standing (from 60+/-4 to 100+/-6 mm Hg) for several hours and improved orthostatic tolerance in all patients. After L-DOPS, blood pressure increases were closely associated with increases in plasma NE levels. Oral administration of carbidopa, which inhibits L-AADC outside the blood-brain barrier, blunted both the increase in plasma NE and the pressor response to L-DOPS in all patients Acute administration of L-DOPS increases blood pressure and improves orthostatic tolerance in patients with NOH. The pressor effect results from conversion of L-DOPS to NE outside the central nervous system.

Apoptotic effects on cultured cells of atmospheric-pressure plasma produced using various gases

NASA Astrophysics Data System (ADS)

Tominami, Kanako; Kanetaka, Hiroyasu; Kudo, Tada-aki; Sasaki, Shota; Kaneko, Toshiro

2016-01-01

This study investigated the effects of low-temperature atmospheric-pressure plasma on various cells such as rat fibroblastic Rat-1 cell line, rat neuroblastoma-like PC12 cell line, and rat macrophage-like NR8383 cell line. The plasma was irradiated directly to a culture medium containing plated cells for 0-20 s. The applied voltage, excitation frequency, and argon or helium gas flow were, respectively, 3-6 kV, 10 kHz, and 3 L/min. Cell viability and apoptotic activity were evaluated using annexin-V/propidium iodide staining. Results showed that the low-temperature atmospheric-pressure plasma irradiation promoted cell death in a discharge-voltage-dependent and irradiation-time-dependent manner. Furthermore, different effects are produced depending on the cell type. Moreover, entirely different mechanisms might be responsible for the induction of apoptosis in cells by helium and argon plasma.

Preliminary characterization of a laser-generated plasma sheet

DOE PAGES

Keiter, P. A.; Malamud, G.; Trantham, M.; ...

2014-12-10

We present the results from recent experiments to create a flowing plasma sheet. Two groups of three laser beams with nominally 1.5 kJ of energy per group were focused to separate pointing locations, driving a shock into a wedge target. As the shock breaks out of the wedge, the plasma is focused on center, creating a sheet of plasma. Measurements at 60 ns indicate the plasma sheet has propagated 2825 microns with an average velocity of 49 microns/ns. These experiments follow previous experiments, which are aimed at studying similar physics as that found in the hot spot region of cataclysmicmore » variables. Krauland et al created a flowing plasma, which represents the flowing plasma from the secondary star. This flow interacted with a stationary object, which represented the disk around the white dwarf. A reverse shock is a shock formed when a freely expanding plasma encounters an obstacle. Reverse shocks can be generated by a blast wave propagating through a medium. As a result, they can also be found in binary star systems where the flowing gas from a companion star interacts with the accretion disk of the primary star.« less

Impurity screening behavior of the high-field side scrape-off layer in near-double-null configurations: prospect for mitigating plasma-material interactions on RF actuators and first-wall components

NASA Astrophysics Data System (ADS)

LaBombard, B.; Kuang, A. Q.; Brunner, D.; Faust, I.; Mumgaard, R.; Reinke, M. L.; Terry, J. L.; Howard, N.; Hughes, J. W.; Chilenski, M.; Lin, Y.; Marmar, E.; Rice, J. E.; Rodriguez-Fernandez, P.; Wallace, G.; Whyte, D. G.; Wolfe, S.; Wukitch, S.

2017-07-01

The impurity screening response of the high-field side (HFS) scrape-off layer (SOL) to localized nitrogen injection is investigated on Alcator C-Mod for magnetic equilibria spanning lower-single-null, double-null and upper-single-null configurations under otherwise identical plasma conditions. L-mode, EDA H-mode and I-mode discharges are investigated. HFS impurity screening is found to depend on magnetic flux balance and the direction of B  ×  \

UPLC-MS/MS assay for the simultaneous determination of ethinyl estradiol, norgestimate and 17-Desacetyl norgestimate at low pg/mL in human plasma.

PubMed

Huang, Mike-Qingtao; Kang, Lijuan; Wang, Weimin; Skee, Donna; Chen, Mu; Lin, Zhongping John; Verhaeghe, Tom; Weng, Naidong

2016-04-01

Previously, because of the difficulty of measuring very low levels (pg/mL) of norgestimate (NGM) due to rapid metabolism to its active and major metabolite, 17-Desacetyl norgestimate (DNGM), only DNGM and the co-administered ethinyl estradiol (EE2) were required to be analyzed in bioequivalence (BE) studies for oral contraceptive NGM/EE2 tablets. Recently, with more sensitive assays available, health authorities have requested that bioequivalence of NGM be also demonstrated in addition to DNGM and EE2. Therefore, it was important to establish a 3-in-1 method for the quantitation of EE2, NGM and DNGM in human plasma. Here a UPLC-MS/MS method for the simultaneous quantitation of EE2, NGM and DNGM in human plasma at low pg/mL range is described. EE2, NGM, DNGM and their isotopic labeled internal standards (IS) EE2-d4, NGM-d6 and DNGM-d6 in 0.4mL of human plasma were extracted with hexane/ethyl acetate. The extracts were evaporated to dryness and derivatized with dansyl chloride, to enhance the mass spec response. The derivatives were reconstituted with methanol and analyzed by UPLC-MS/MS. In order to minimize the ex-vivo conversion of NGM to DNGM, sodium fluoride/potassium oxalate was used as anti-coagulant. To achieve desirable throughput for sample analysis, UPLC-MS/MS with a run time of 4.4min was utilized. The calibration curve ranges were 5-500pg/mL for EE2 and NGM, and 25-2500pg/mL for DNGM, respectively. The chromatographic separation was achieved on a Waters Acquity UPLC HSS T3 (100×2.1mm, 1.8μm) column with a gradient elution. Assay accuracy, precision, linearity, selectivity, sensitivity and analyte stability covering sample storage and analysis were established. This validated UPLC-MS/MS method has been applied to a BE study for the determination of EE2, NGM and DNGM concentrations in human plasma. Copyright © 2016 Elsevier B.V. All rights reserved.

Computational-aided design of molecularly imprinted polymer for selective extraction of methadone from plasma and saliva and determination by gas chromatography.

PubMed

Ahmadi, F; Rezaei, H; Tahvilian, R

2012-12-28

The main objective of this research was computational designing of an imprinted polymer for selective solid phase extraction (SPE) of methadone from plasma and saliva samples analyzed by gas chromatography-flam ionization detector (GC-FID). The density functional theory (DFT) at B3LYP/6-31G+ (d, p) level and Gaussian 2003 package was used to calculate the interaction energy of template-monomers (ΔE). The effect of polymerization solvent was also studied using polarizable continuum model (PCM). It was shown that, methacrylic acid (MAA) gave the largest ΔE in acetonitrile as a polymerization solvent. To examine the validity of this approach, two MIP were synthesized for methadone as template molecule and methacrylic acid as functional monomer in acetonitrile (AN) and methanol (MeOH), respectively. The performance of each polymer was evaluated by using imprinting effect. As it is expected, the best results were obtained for the molecularly imprinted polymer (MIP) which was prepared in AN. For the optimized method, the linearity between responses (peak areas) and concentration of methadone in plasma and saliva samples were found over the range of 3.6-40,000 ng mL(-1) (R(2)=0.997) and 3.0-40,000 ng mL(-1) (R(2)=0.998), respectively. The limit of detection (LOD) and limit of quantification (LOQ) for methadone in plasma were calculated to be 2.45 and 3.6 ng mL(-1), respectively. The LOD and LOQ for methadone in saliva were 2.14 and 3.0 ng mL(-1), respectively. The relative standard deviation (RSD; n=4) for plasma samples containing 10, 100, 500, 1000 ng mL(-1)of methadone were 5.98, 5.78, 5.52, 4.78, 4.74, and the RSD (n=4) for saliva sample containing 5, 20, 100, 1000 ng mL(-1) of methadone were 4.74, 5.1, 5.9, 5.6, respectively. Copyright © 2012 Elsevier B.V. All rights reserved.

A cellular backline: specialization of host membranes for defence.

PubMed

Faulkner, Christine

2015-03-01

In plant-pathogen interactions, the host plasma membrane serves as a defence front for pathogens that invade from the extracellular environment. As such, the lipid bilayer acts as a scaffold that targets and delivers defence responses to the site of attack. During pathogen infection, numerous changes in plasma membrane composition, organization, and structure occur. There is increasing evidence that this facilitates the execution of a variety of responses, highlighting the regulatory role membranes play in cellular responses. Membrane microdomains such as lipid rafts are hypothesized to create signalling platforms for receptor signalling in response to pathogen perception and for callose synthesis. Further, the genesis of pathogen-associated structures such as papillae and the extra-haustorial membrane necessitates polarization of membranes and membrane trafficking pathways. Unlocking the mechanisms by which this occurs will enable greater understanding of how targeted defences, some of which result in resistance, are executed. This review will survey some of the changes that occur in host membranes during pathogen attack and how these are associated with the generation of defence responses. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Eester, D.; Lerche, E.

Both at low and higher cyclotron harmonics, properly accounting for finite Larmor radius effects is crucial in many ion cyclotron resonance frequency heating scenarios creating high energy tails. The present paper discusses ongoing work to extend the 1D TOMCAT wave equation solver [D. Van Eester and R. Koch, Plasma Phys. Contr. Fusion 40 (1998) 1949] to arbitrary harmonics and arbitrary wavelengths. Rather than adopting the particle position, the guiding center position is used as the independent variable when writing down an expression for the dielectric response. Adopting a philosophy originally due to Kaufman [A.N. Kaufman, Phys. Fluids 15 (1972) 1063],more » the relevant dielectric response in the Galerkin formalism is written in a form where the electric field and the test function vector appear symmetrically, which yields a power balance equation that guarantees non-negative absorption for any wave type for Maxwellian plasmas. Moreover, this choice of independent variable yields intuitive expressions that can directly be linked to the corresponding expressions in the RF diffusion operator. It also guarantees that a positive definite power transfer from waves to particles is ensured for any of the wave modes in a plasma in which all populations have a Maxwellian distribution, as is expected from first principles. Rather than relying on a truncated Taylor series expansion of the dielectric response, an integro-differential approach that retains all finite Larmor radius effects [D. Van Eester and E. Lerche, Plasma Phys. Control. Fusion 55 (2013) 055008] is proposed.« less

Integro-differential modeling of ICRH wave propagation and damping at arbitrary cyclotron harmonics and wavelengths in tokamaks

NASA Astrophysics Data System (ADS)

Van Eester, D.; Lerche, E.

2014-02-01

Both at low and higher cyclotron harmonics, properly accounting for finite Larmor radius effects is crucial in many ion cyclotron resonance frequency heating scenarios creating high energy tails. The present paper discusses ongoing work to extend the 1D TOMCAT wave equation solver [D. Van Eester & R. Koch, Plasma Phys. Contr. Fusion 40 (1998) 1949] to arbitrary harmonics and arbitrary wavelengths. Rather than adopting the particle position, the guiding center position is used as the independent variable when writing down an expression for the dielectric response. Adopting a philosophy originally due to Kaufman [A.N. Kaufman, Phys. Fluids 15 (1972) 1063], the relevant dielectric response in the Galerkin formalism is written in a form where the electric field and the test function vector appear symmetrically, which yields a power balance equation that guarantees non-negative absorption for any wave type for Maxwellian plasmas. Moreover, this choice of independent variable yields intuitive expressions that can directly be linked to the corresponding expressions in the RF diffusion operator. It also guarantees that a positive definite power transfer from waves to particles is ensured for any of the wave modes in a plasma in which all populations have a Maxwellian distribution, as is expected from first principles. Rather than relying on a truncated Taylor series expansion of the dielectric response, an integro-differential approach that retains all finite Larmor radius effects [D. Van Eester & E. Lerche, Plasma Phys. Control. Fusion 55 (2013) 055008] is proposed.

The Nitric Oxide Synthase Inhibitor NG-Nitro-L-Arginine Methyl Ester Diminishes the Immunomodulatory Effects of Parental Arginine in Rats with Subacute Peritonitis

PubMed Central

Lo, Hui-Chen; Hung, Ching-Yi; Huang, Fu-Huan; Su, Tzu-Cheng; Lee, Chien-Hsing

2016-01-01

The combined treatment of parenteral arginine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) have been shown to improve liver function and systemic inflammation in subacute peritonitic rats. Here, we investigated the effects of single and combined parenteral arginine and L-NAME treatments on leukocyte and splenocyte immunity. Male Wistar rats were subjected to cecal punctures and were intravenously given total parenteral nutrition solutions with or without arginine and/or L-NAME supplementations for 7 days. Non-surgical and sham-operated rats with no cecal puncture were given a chow diet and parenteral nutrition, respectively. Parenteral feeding elevated the white blood cell numbers and subacute peritonitis augmented the parenteral nutrition-induced alterations in the loss of body weight gain, splenomegaly, and splenocyte decreases. Parenteral arginine significantly increased the B-leukocyte level, decreased the natural killer T (NKT)-leukocyte and splenocyte levels, alleviated the loss in body weight gain and total and cytotoxic T-splenocyte levels, and attenuated the increases in plasma nitrate/nitrite and interferon-gamma production by T-splenocytes. L-NAME infusion significantly decreased NKT-leukocyte level, tumor-necrosis factor (TNF)-alpha production by T-splenocytes and macrophages, and interferon-gamma production by T-leukocytes, monocytes, and T-splenocytes, as well as increased interleukin-6 production by T-leukocytes and monocytes and nitrate/nitrite production by T-leukocytes. Combined treatment significantly decreased plasma nitrate/nitrite, the NKT-leukocyte level, and TNF-alpha production by T-splenocytes. Parenteral arginine may attenuate immune impairment and L-NAME infusion may augment leukocyte proinflammatory response, eliminate splenocyte proinflammatory and T-helper 1 responses, and diminish arginine-induced immunomodulation in combined treatment in subacute peritonitic rats. PMID:27007815

Neurocirculatory abnormalities in Parkinson disease with orthostatic hypotension: independence from levodopa treatment.

PubMed

Goldstein, David S; Eldadah, Basil A; Holmes, Courtney; Pechnik, Sandra; Moak, Jeffrey; Saleem, Ahmed; Sharabi, Yehonatan

2005-12-01

Patients with Parkinson disease often have orthostatic hypotension. Neurocirculatory abnormalities underlying orthostatic hypotension might reflect levodopa treatment. Sixty-six Parkinson disease patients (36 with orthostatic hypotension, 15 off and 21 on levodopa; 30 without orthostatic hypotension) had tests of reflexive cardiovagal gain (decrease in interbeat interval per unit decrease in systolic pressure during the Valsalva maneuver; orthostatic increase in heart rate per unit decrease in pressure); reflexive sympathoneural function (decrease in pressure during the Valsalva maneuver; orthostatic increment in plasma norepinephrine); and cardiac and extracardiac noradrenergic innervation (septal myocardial 6-[18F]fluorodopamine-derived radioactivity; supine plasma norepinephrine). Severity of orthostatic hypotension did not differ between the levodopa-untreated and levodopa-treated groups with Parkinson disease and orthostatic hypotension (-52+/-6 [SEM] versus -49+/-5 mm Hg systolic). The 2 groups had similarly low reflexive cardiovagal gain (0.84+/-0.23 versus 1.33+/-0.35 ms/mm Hg during Valsalva; 0.43+/-0.09 versus 0.27+/-0.06 bpm/mm Hg during orthostasis); and had similarly attenuated reflexive sympathoneural responses (97+/-29 versus 71+/-23 pg/mL during orthostasis; -82+/-10 versus -73+/-8 mm Hg during Valsalva). In patients off levodopa, plasma norepinephrine was lower in those with (193+/-19 pg/mL) than without (348+/-46 pg/mL) orthostatic hypotension. Low values for reflexive cardiovagal gain, sympathoneural responses, and noradrenergic innervation were strongly related to orthostatic hypotension. Parkinson disease with orthostatic hypotension features reflexive cardiovagal and sympathoneural failure and cardiac and partial extracardiac sympathetic denervation, independent of levodopa treatment.

The physiological responses of green sturgeon (Acipenser medirostris) to potential global climate change stressors.

PubMed

Sardella, Brian A; Kültz, Dietmar

2014-01-01

The green sturgeon (Acipenser medirostris) is an anadromous species with a distinct population segment in the San Francisco Bay-Sacramento River Delta that is currently listed as threatened. Although this species is able to tolerate salinity challenges as soon as 6 mo posthatch, its ability to deal with unpredictable salinity fluctuations remains unknown. Global climate change is predicted to result in large freshwater (FW) flushes through the estuary during winter and greater tidal influence during the summer. We exposed green sturgeon acclimated to 15 (EST) or 24 (BAY) g/L salinity to a rapid FW influx, where salinity was reduced to 0 g/L in 3 h in order to simulate the effect of the "winter" scenario. Both groups survived, enduring a 10% plasma osmolality reduction after 3 h. BAY-acclimated sturgeon upregulated both Na(+), K(+)-ATPase (NKA) activity and caspase 3/7 activity, but no changes were observed in the EST-acclimated fish. In addition, we exposed FW-acclimated sturgeon to a dual 12-h salinity fluctuation cycle (0-24-0 g/L) in order to simulate the effect of greater tidal influence. At 6 h, the sturgeon showed a significant increase in plasma osmolality, and branchial NKA and caspase 3/7 activities were increased, indicating an acclimation response. There was no acclimation at 18 h, and plasma osmolality was higher than the peak observed at 6 h. The second fluctuation elicited an upregulation of the stress proteins ubiquitin and heat shock 70-kDa protein (HSP 70). Sturgeon can acclimate to changes in salinity; however, salinity fluctuations resulted in substantial cellular stress.

Lambda light chain revision in the human intestinal IgA response.

PubMed

Su, Wen; Gordon, John N; Barone, Francesca; Boursier, Laurent; Turnbull, Wayne; Mendis, Surangi; Dunn-Walters, Deborah K; Spencer, Jo

2008-07-15

Revision of Ab L chains by secondary rearrangement in mature B cells has the potential to change the specific target of the immune response. In this study, we show for the first time that L chain revision is normal and widespread in the largest Ab producing population in man: intestinal IgA plasma cells (PC). Biases in the productive and non-productive repertoire of lambda L chains, identification of the circular products of rearrangement that have the characteristic biases of revision, and identification of RAG genes and protein all reflect revision during normal intestinal IgA PC development. We saw no evidence of IgH revision, probably due to inappropriately orientated recombination signal sequences, and little evidence of kappa-chain revision, probably due to locus inactivation by the kappa-deleting element. We propose that the lambda L chain locus is available and a principal modifier and diversifier of Ab specificity in intestinal IgA PCs.

Effects of model aromatizable (17α-methyltestosterone) and non-aromatizable (5α-dihydrotestosterone) androgens on the adult mummichog (Fundulus heteroclitus) in a short-term reproductive endocrine bioassay.

PubMed

Rutherford, Robert; Lister, Andrea; Hewitt, L Mark; MacLatchy, Deborah

2015-04-01

Androgens originating from pulp mill processing, sewage treatment facilities and agricultural activities have the potential for discharge into aquatic receiving environments. To assess androgen effects on reproductive endocrine status in fish in estuarine environments, male and female adult northern mummichog (Fundulus heteroclitus macrolepidotus) were exposed to an aromatizable androgen (17α-methyltestosterone; MT) and a non-aromatizable androgen (5α-dihydrotestosterone; DHT) in a short-term reproductive endocrine bioassay. Fish were nominally exposed to 10 μg/L or 100 μg/L DHT, or 0.1 μg/L or 1 μg/L MT for 14 days during gonadal recrudescence. Actual concentrations of androgens, as measured by enzyme immunoassay (EIA), were 10-49% of nominal MT 0.1, 3-6% of nominal MT 1, 5-10% of nominal DHT 10 and 3-25% of nominal DHT 100. Female mummichog were impacted to a greater degree by androgen exposure, with increased plasma testosterone (T) at 100 μg/L DHT, depressed plasma 17β-estradiol (E2) at both DHT concentrations and at 1 μg/L MT, as well as depressed in vitro E2 at both MT concentrations and 100 μg/L DHT. Males had depressed plasma T in the 10 μg/L DHT treatment and depressed in vitro 11-ketotestosterone production for both MT concentrations and 10 μg/L DHT. Ovarian aromatase gene expression was induced in females exposed to 1 μg/L MT. DHT at 100 μg/L increased hepatic vitellogenin-1 (VTG1) expression in males and depressed VTG1 expression in females. The range of responses between sexes and among species provides evidence for modes of actions and potential impacts of androgens in aquatic receiving environments. Copyright © 2015 Elsevier Inc. All rights reserved.

Cortisol and interleukin-6 responses during intermittent exercise in two different hot environments with equivalent WBGT.

PubMed

Wright, Heather E; McLellan, Tom M; Stapleton, Jill M; Hardcastle, Stephen G; Kenny, Glen P

2012-01-01

Blood marker concentrations such as cortisol (COR) and interleukin (IL)-6 are commonly used to evaluate the physiological strain associated with work in the heat. It is unclear, however, if hot environments of an equivalent thermal stress, as defined by a similar wet bulb globe temperature (WBGT), result in similar response patterns. This study examined markers of neuroendocrine (COR) and immune (IL-6) responses, as well as the cardiovascular and thermal responses, relative to changes in body heat content measured by whole-body direct calorimetry during work in two different hot environments with equivalent WBGT. Eight males performed a 2-hr heavy intermittent exercise protocol (six 15-min bouts of cycling at a constant rate of metabolic heat production (360W) interspersed by 5-min rest periods) in Hot/Dry (46°C, 10% relative humidity [RH]) and Warm/Humid (33°C, 60% RH) conditions (WBGT ∼ 29°C). Whole-body evaporative and dry heat exchange, change in body heat content (ΔH(b)), rectal temperature (T(re)), and heart rate were measured continuously. Venous blood was obtained at rest (PRE) and the end of each exercise bout for the measurement of changes in plasma volume (PV), plasma protein (an estimate of plasma water changes), COR, and IL-6. Ratings of perceived exertion and thermal sensation were measured during the last minute of each exercise bout. No differences existed for ΔH(b), heart rate, T(re),%ΔPV, plasma protein concentration, perceptual strain (thermal sensation, perceived exertion), and COR between the Hot/Dry and Warm/Humid conditions. IL-6 exhibited an interaction effect (p = 0.041), such that greater increases were observed in the Hot/Dry (Δ = 1.61 pg·mL(-1)) compared with the Warm/Humid (Δ = 0.64 pg·mL(-1)) environment. These findings indicate that work performed in two different hot environments with equivalent WBGT resulted in similar levels of thermal, cardiovascular, and perceptual strain, which support the use of the WBGT stress index. However, the greater IL-6 response in the Hot/Dry requires further research to elucidate the effects of different hot environments and work intensities.

Morphology of high-latitude plasma density perturbations as deduced from the total electron content measurements onboard the Swarm constellation

NASA Astrophysics Data System (ADS)

Park, Jaeheung; Lühr, Hermann; Kervalishvili, Guram; Rauberg, Jan; Stolle, Claudia; Kwak, Young-Sil; Lee, Woo Kyoung

2017-01-01

In this study, we investigate the climatology of high-latitude total electron content (TEC) variations as observed by the dual-frequency Global Navigation Satellite Systems (GNSS) receivers onboard the Swarm satellite constellation. The distribution of TEC perturbations as a function of geographic/magnetic coordinates and seasons reasonably agrees with that of the Challenging Minisatellite Payload observations published earlier. Categorizing the high-latitude TEC perturbations according to line-of-sight directions between Swarm and GNSS satellites, we can deduce their morphology with respect to the geomagnetic field lines. In the Northern Hemisphere, the perturbation shapes are mostly aligned with the L shell surface, and this anisotropy is strongest in the nightside auroral (substorm) and subauroral regions and weakest in the central polar cap. The results are consistent with the well-known two-cell plasma convection pattern of the high-latitude ionosphere, which is approximately aligned with L shells at auroral regions and crossing different L shells for a significant part of the polar cap. In the Southern Hemisphere, the perturbation structures exhibit noticeable misalignment to the local L shells. Here the direction toward the Sun has an additional influence on the plasma structure, which we attribute to photoionization effects. The larger offset between geographic and geomagnetic poles in the south than in the north is responsible for the hemispheric difference.

Effect of oral amino acids on counterregulatory responses and cognitive function during insulin-induced hypoglycemia in nondiabetic and type 1 diabetic people.

PubMed

Rossetti, Paolo; Porcellati, Francesca; Busciantella Ricci, Natalia; Candeloro, Paola; Cioli, Patrizia; Nair, K Sreekumaran; Santeusanio, Fausto; Bolli, Geremia B; Fanelli, Carmine G

2008-07-01

Amino acids stimulate glucagon responses to hypoglycemia and may be utilized by the brain. The aim of this study was to assess the responses to hypoglycemia in nondiabetic and type 1 diabetic subjects after ingestion of an amino acid mixture. Ten nondiabetic and 10 diabetic type 1 subjects were studied on three different occasions during intravenous insulin (2 mU . kg(-1) . min(-1)) plus variable glucose for 160 min. In two studies, clamped hypoglycemia (47 mg/dl plasma glucose for 40 min) was induced and either oral placebo or an amino acid mixture (42 g) was given at 30 min. In the third study, amino acids were given, but euglycemia was maintained. Plasma glucose and insulin were no different in the hypoglycemia studies with both placebo and amino acids (P > 0.2). After the amino acid mixture, plasma amino acid concentrations increased to levels observed after a mixed meal (2.4 +/- 0.13 vs. placebo study 1.7 +/- 0.1 mmol/l, P = 0.02). During clamped euglycemia, ingestion of amino acids resulted in transient increases in glucagon concentrations, which returned to basal by the end of the study. During clamped hypoglycemia, glucagon response was sustained and increased more in amino acid studies versus placebo in nondiabetic and diabetic subjects (P < 0.05), but other counter-regulatory hormones and total symptom score were not different. Beta-OH-butyrate was less suppressed after amino acids (200 +/- 15 vs. 93 +/- 9 micromol/l, P = 0.01). Among the cognitive tests administered, the following indicated less deterioration after amino acids than placebo: Trail-Making part B, PASAT (Paced Auditory Serial Addition Test) (2 s), digit span forward, Stroop colored words, and verbal memory tests for nondiabetic subjects; and Trail-Making part B, digit span backward, and Stroop color tests for diabetic subjects. Oral amino acids improve cognitive function in response to hypoglycemia and enhance the response of glucagon in nondiabetic and diabetic subjects.

Proteasome 20S in multiple myeloma: comparison of concentration and chymotrypsin-like activity in plasma and serum.

PubMed

Romaniuk, Wioletta; Kalita, Joanna; Ostrowska, Halina; Kloczko, Janusz

2018-03-05

The ubiquitin-proteasome system is relevant in the pathobiology of many haematological malignancies, including multiple myeloma. The assessment of proteasome concentration and chymotrypsin-like (ChT-L) activity might constitute a new approach to diagnosis, prognosis and monitoring of anticancer treatment of patients with haematological malignancies and other diseases. The aim of our study was to determine which material, plasma or serum, is better for measuring chymotrypsin-like (ChT-L) activity and proteasome concentration. We analysed proteasome concentration and chymotrypsin-like (ChT-L) activity in 70 plasma and serum samples drawn from 28 patients at different treatment stages for multiple myeloma (MM) and 31 healthy volunteers. Proteasome ChT-L activity and concentration in multiple myeloma patients were significantly higher in plasma compared to serum. In this group we observed significant and positive correlations both between the plasma and serum proteasome ChT-L activity and plasma and serum proteasome concentration. The higher values of proteasome concentration and ChT-L activity in plasma than in serum and their better correlations with parameters of tumour load and prognosis suggest that plasma constitutes a better biological material for measuring ChT-L activity and proteasome concentration than serum in multiple myeloma patients.

Cold plasma processing technology makes advances

USDA-ARS?s Scientific Manuscript database

Cold plasma (AKA nonthermal plasma, cool plasma, gas plasma, etc.) is a rapidly maturing antimicrobial process being developed for applications in the food industry. A wide array of devices can be used to create cold plasma, but the defining characteristic is that they operate at or near room temper...

Final Report on Development of Optimized Field-Reversed Configuration Plasma Formation Techniques for Magnetized Target Fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lynn, Alan

2013-11-01

The University of New Mexico (UNM) proposed a collaboration with Los Alamos National Laboratory (LANL) to develop and test methods for improved formation of field-reversed configuration (FRC) plasmas relevant to magnetized target fusion (MTF) energy research. MTF is an innovative approach for a relatively fast and cheap path to the production of fusion energy that utilizes magnetic confinement to assist in the compression of a hot plasma to thermonuclear conditions by an external driver. LANL is currently pursing demonstration of the MTF concept via compression of an FRC plasma by a metal liner z-pinch in conjunction with the Air Forcemore » Research Laboratory in Albuquerque, NM. A key physics issue for the FRC's ultimate success as an MTF target lies in the initial pre-ionization (PI) stage. The PI plasma sets the initial conditions from which the FRC is created. In particular, the PI formation process determines the amount of magnetic flux that can be trapped to form the FRC. A ringing theta pinch ionization (RTPI) technique, such as currently used by the FRX-L device at LANL, has the advantages of high ionization fraction, simplicity (since no additional coils are required), and does not require internal electrodes which can introduce impurities into the plasma. However RTPI has been shown to only trap 50% of the initial bias flux at best and imposes additional engineering constraints on the capacitor banks. The amount of trapped flux plays an important role in the FRC's final equilibrium, transport, and stability properties, and provides increased ohmic heating of the FRC through induced currents as the magnetic field decays. Increasing the trapped flux also provides the route to greatest potential gains in FRC lifetime, which is essential to provide enough time to translate and compress the FRC effectively. In conjunction with LANL we initially planned to develop and test a microwave break- down system to improve the initial PI plasma formation. The UNM team would design the microwave optics and oversee the fabrication and assembly of all components and assist with integration into the FRX-L machine control system. LANL would provide a preexisting 65 kW X-band microwave source and some associated waveguide hardware. Once constructed and installed, UNM would take the lead in operating the microwave breakdown system and conducting studies to optimize its use in FRC PI formation in close cooperation with the needs of the LANL MTF team. In conjunction with our LANL collaborators, we decided after starting the project to switch from a microwave plasma breakdown approach to a plasma gun technology to use for enhanced plasma formation in the FRX-L field-reversed configuration experiment at LANL. Plasma guns would be able to provide significantly higher density plasma with greater control over its distribution in time and space within the experiment. This would allow greater control and ne-tuning of the PI plasma formed in the experiment. Multiple plasma guns would be employed to fill a Pyrex glass test chamber (built at UNM) with plasma which would then be characterized and optimized for the MTF effort.« less

[The changes of ghrelin, growth hormone, growth hormone releasing hormone and their clinical significances in patients with chronic obstructive pulmonary disease].

PubMed

Xu, Zhi-song; Bao, Zi-yu; Wang, Zhi-ying; Yang, Guo-jun; Zhu, Dong-fang; Zhang, Li; Tan, Rong-mei

2012-07-01

To investigate the changes of plasma ghrelin, growth hormone (GH) and growth hormone releasing hormone (GHRH) and gastric ghrelin in patients with chronic obstructive pulmonary disease (COPD) and to explore their clinical significances. Plasma ghrelin, GH, GHRH, TNFα, IL-6 and C reactive protein (CRP) were measured in 40 COPD patients and 20 controls with chronic bronchitis. Correlated factors of plasma ghrelin, TNFα, IL-6, CRP were analyzed. Body composition was assessed with bioelectrical impedance analysis. The expression of gastric ghrelin in patients with COPD was detected. Plasma ghrelin was higher in the underweight patients than in the normal weight patients and in the controls [(1.78 ± 0.46) ng/L, (1.39 ± 0.46) ng/L, (1.36 ± 0.39) ng/L, respectively]. Plasma GH was lower in the underweight patients than in the normal weight patients and in the controls [(4.12 ± 0.83) µg/L, (5.17 ± 0.72)µg/L, (6.49 ± 1.13) µg/L, respectively]. Plasma GHRH was lower in the underweight patients than in the normal weight patients and in the controls [(20.43 ± 4.41) ng/L, (23.47 ± 3.97) ng/L, (27.48 ± 10.06) ng/L, respectively]. Plasma ghrelin was higher in the underweight patients than in the controls (P < 0.01). Plasma ghrelin was higher in the underweight patients than in the normal weight patients with COPD. Plasma ghrelin (log transformed) was negatively correlated with BMI and percentage of body fat in the COPD patients. Plasma GHRH was positively correlated with ghrelin in the underweight patients (r = 0.515, P < 0.05), while no correlation was found between plasma GH and ghrelin in the underweight patients (r = 0.415, P > 0.05). Plasma ghrelin was positively correlated with TNFα and IL-6 in the underweight patients. The gastric expression of ghrelin showed no evident difference between the patients with COPD and the controls. The plasma GH in COPD patients may not be correlated with ghrelin. The plasma ghrelin level may be a useful indicator for malnutrition in COPD patients. Plasma ghrelin might be involved in the pathogenesis of CODP by affecting the body energy metabolism.

Parasite-specific IL-17-type cytokine responses and soluble IL-17 receptor levels in Alveolar Echinococcosis patients.

PubMed

Lechner, Christian J; Grüner, Beate; Huang, Xiangsheng; Hoffmann, Wolfgang H; Kern, Peter; Soboslay, Peter T

2012-01-01

Alveolar Echinococcosis (AE) caused by the cestode Echinococcus multilocularis, is a severe helminth infection of man, where unrestricted parasite growth will ultimately result in organ failure and fatality. The tissue-infiltrative growth of the larval metacestode and the limited efficacy of available drugs complicate successful intervention in AE; patients often need life-long medication, and if possible, surgical resection of affected tissues and organs. Resistance to AE has been reported, but the determinants which confer protection are not known. ln this study, we analyzed in patients at distinct stages of Alveolar Echirococcosis, that is cured, stable and progressive AE, as well as in infection-free controls, the cellular production and plasma levels of pro-inflammatory cytokines lL-17A, lL-17B, lL-17F and their soluble receptors lL-17RA (slL-17RA) and IL-17RB (sIL-17RB). Significantly elevated levels of IL-17B and slL-17RB were observed, whilst lL-17F and slL-17RA were reduced in patients with AE. Similarly, the cellular production of lL-17F and slL-L7RA in response to E. multilocularis antigens was low in AE patients, while levels of slL-17RB were highly enhanced. These observations suggest immune-modulating properties of E. multitocularis on lL-17 cytokine-mediated pro-inflammatory immune responses; this may facilitate the tissue infiltrative growth of the parasite and its persistence in the human host.

Surface Roughness of Various Diamond-Like Carbon Films

NASA Astrophysics Data System (ADS)

Liu, Dongping; Liu, Yanhong; Chen, Baoxiang

2006-11-01

Atomic force microscopy is used to estimate and compare the surface morphology of hydrogenated and hydrogen-free diamond-like carbon (DLC) films. The films were prepared by using DC magnetron sputtering of a graphite target, pulsed cathodic carbon arcs, electron cyclotron resonance (ECR), plasma source ion implantation and dielectric barrier discharge (DBD). The difference in the surface structure is presented for each method of deposition. The influences of various discharge parameters on the film surface properties are discussed based upon the experimental results. The coalescence process via the diffusion of adsorbed carbon species is responsible for the formation of hydrogen-free DLC films with rough surfaces. The films with surface roughness at an atomic level can be deposited by energetic ion impacts in a highly ionized carbon plasma. The dangling bonds created by atomic hydrogen lead to the uniform growth of hydrocarbon species at the a-C:H film surfaces of the ECR or DBD plasmas.

[Aldosterone response to various stimuli in hyperthyroidism: in vivo and in vitro studies].

PubMed

Kigoshi, T; Kaneko, M; Nakano, S; Azukizawa, S; Uchida, K; Morimoto, S

1993-06-20

Responses of plasma aldosterone (PA) to alpha-ACTH-(1-24) (250 micrograms, im) injection and graded angiotensin II (AII) infusions (2, 4 and 8ng/kg/min for 30 min at each dose) on a constant sodium intake (170mEq daily) were assessed in 17 patients with Basedow's disease and 13 age-matched normal subjects. Aldosterone production in response to ACTH, AII and potassium in adrenal zona glomerulosa cells from L-thyroxine-induced hyperthyroid rats (H-rats) were also examined. Basal levels of plasma renin activity (PRA) and urinary aldosterone excretion were significantly higher (p < 0.01 and p < 0.05, respectively) in the patients with Basedow's disease than in the normal subjects, whereas basal PA level was similar in the two groups. The ACTH injection induced similar increases in plasma cortisol, plasma 18-hydroxycorticosterone (18-OHB) and PA in the two groups. The graded AII infusions also produced increases in plasma 18-OHB and PA in the two groups. Responses of these two corticosteroids to AII were, however, significantly lower (p < 0.05) in the patients with Basedow's disease than in the normal subjects. In the experimental animal study, basal PRA levels and the adrenal glomerulosa cell count/adrenal were significantly higher (p < 0.05) in the H-rats than in the control rats, whereas basal PA levels were similar in the two groups. Aldosterone production in response to AII, ACTH, and potassium increased in a dose-dependent manner in the two groups. Responses of aldosterone production to AII were, however, significantly lower (p < 0.05) in the H-rats than in the control rats. These results suggest that the impaired responsiveness of adrenal zona glomerulosa cells to AII, as well as an increased metabolic clearance rate of aldosterone, may be involved in the abnormal aldosterone metabolism in hyperthyroidism.

Ubiquitin C-Terminal Hydrolase-L1 as a Biomarker for Ischemic and Traumatic Brain Injury in Rats

DTIC Science & Technology

2010-01-01

specific enolase increases in plasma during and immediately after extracorporeal circulation . Ann. Thorac. Surg., 69, 750– 754. Johnston, S.C., Riddle, S.M...and eventually into circulating blood. Materials and methods Materials Sodium bicarbonate was from Sigma (St Louis, MO, USA) (catalog no. C-3041...ischemia is responsible for its release into circulating blood. In this study, the potential of UCH-L1 as a biofluid-based protein biomarker for two

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. II. Pharmacokinetics and pharmacodynamics of once weekly administration of testosterone enanthate.

PubMed

Anderson, R A; Wu, F C

1996-03-01

Hormonal suppression of spermatogenesis is currently being investigated as a method of reversible male contraception. However, administration of exogenous testosterone (T) induces azoospermia in only 40-70% of Caucasian men, whereas the remainder suppresses to severe oligozoospermia (< 5 x 10(5)/mL). The reason(s) for the heterogeneity in the spermatogenic response is not clear. We have prospectively investigated the possibilities that higher plasma concentrations of T and/or differences in the extent and rate of gonadotropin suppression could maintain a low level of spermatogenesis in subjects taking part in a clinical efficacy trial of hormonal male contraception. Thirty-three healthy adult men, aged 21-41 yr, were given 200 mg T enanthate (TE), im, weekly for up to 18 months. Azoospermia was achieved in 18 men (55%) after 20 weeks of treatment, at which time the remaining 15 (45%) stabilized at a mean sperm density of 2.0 +/- 0.8 (+/- SD) x 10(6)/mL. These 15 subjects remained oligozoospermic for the rest of the efficacy study. To compare the pharmacokinetics and pharmacodynamics of TE between the azoospermic and oligozoospermic responders, plasma samples were obtained immediately before and 1, 2, 4, and 7 days after the 1st and 16th TE injections. Further samples were taken after 2, 4, 8, and 12 weeks of treatment. Plasma concentrations of total, free, and non-sex hormone-binding globulin (non-SHBG)-bound T, estradiol, LH, and FSH were measured. Compared to baseline, preinjection levels of total T increased 2.5-fold, reaching a steady state around 12 weeks of treatment. Peak concentrations of total T increased by 5-fold, but free and non-SHBG-bound T levels were increased by 10-fold after 16 weeks. The plasma levels of estradiol showed similar changes as T. However, neither T (bound or free) nor estradiol was significantly different between azoospermic and oligozoospermic responders. Plasma SHBG was reduced to a similar degree in both groups of men after 16 weeks of TE treatment. Plasma concentrations of both LH and FSH decreased rapidly after the first TE injection; a significant decline in LH was detectable after 24 h. Mean levels of both gonadotropins decreased to less than 0.5 U/L by the end of 4 weeks and to below the limit of sensitivity of the assays (0.05 IU/L) by 12 weeks. There were no significant differences in plasma concentrations of LH or FSH or in the rates of suppression between azoospermic and oligozoospermic responders. We conclude that the polymorphism of spermatogenic suppression in response to exogenous T is unlikely to be due to differences in the pharmacokinetics or pharmacodynamics of TE or in the sensitivity of the hypothalamo-pituitary-testicular axis to sex steroid inhibition. Measurements of total plasma T considerably underestimate the increase in bioavailable T during the weekly TE regimen.

Extensions, Validation, and Clinical Applications of a Feedback Control System Simulator of the Hypothalamo-Pituitary-Thyroid Axis

PubMed Central

Samuels, Mary; DiStefano, Joseph J.

2008-01-01

Background We upgraded our recent feedback control system (FBCS) simulation model of human thyroid hormone (TH) regulation to include explicit representation of hypothalamic and pituitary dynamics, and updated TH distribution and elimination (D&E) parameters. This new model greatly expands the range of clinical and basic science scenarios explorable by computer simulation. Methods We quantified the model from pharmacokinetic (PK) and physiological human data and validated it comparatively against several independent clinical data sets. We then explored three contemporary clinical issues with the new model: combined triiodothyronine (T3)/thyroxine (T4) versus T4-only treatment, parenteral levothyroxine (L-T4) administration, and central hypothyroidism. Results Combined T3/T4 therapy—In thyroidectomized patients, the L-T4–only replacement doses needed to normalize plasma T3 or average tissue T3 were 145 μg L-T4/day or 165 μgL-T4/day, respectively. The combined T4 + T3 dosing needed to normalize both plasma and tissue T3 levels was 105 μg L-T4 + 9 μgT3 per day. For all three regimens, simulated mean steady-state plasma thyroid-stimulating hormone (TSH), T3, and T4 was within normal ranges (TSH: 0.5–5 mU/L; T4: 5–12 μg/dL; T3: 0.8–1.9 ng/mL). Parenteral T4 administration—800 μg weekly or 400 μg twice weekly normalized average tissue T3 levels both for subcutaneous (SC) and intramuscular (IM) routes of administration. TSH, T3, and T4 levels were maintained within normal ranges for all four of these dosing schemes (1× vs. 2× weekly, SC vs. IM). Central hypothyroidism—We simulated steady-state plasma T3,T4, and TSH concentrations in response to varying degrees of central hypothyroidism, reducing TSH secretion from 50% down to 0.1% of normal. Surprisingly, TSH, T3, and T4 plasma concentrations remained within normal ranges for TSH secretion as low as 25% of normal. Conclusions Combined T3/T4 treatment—Simulated standard L-T4–only therapy was sufficient to renormalize average tissue T3 levels and maintain normal TSH, T3, and T4 plasma levels, supporting adequacy of standard L-T4–only treatment. Parenteral T4 administration—TSH, T3, and T4 levels were maintained within normal ranges for all four of these dosing schemes (1× vs. 2× weekly, SC vs. IM), supporting these therapeutic alternatives for patients with compromised L-T4 gut absorption. Central hypothyroidism—These results highlight how highly nonlinear feedback in the hypothalamic-pituitary-thyroid axis acts to maintain normal hormone levels, even with severely reduced TSH secretion. PMID:18844475

Characteristics and time evolution of a hollow cathode produced glow discharge plasma in air

NASA Astrophysics Data System (ADS)

Gregor, Joseph Atilla

Current radar systems use mechanical directors and phased array technology for beam steering. Use of a sheet plasma as a microwave reflector promises several advantages over these methods. Operation is inherently broad-band, since all frequencies below the plasma frequency are reflected. The orientation and shape of the reflector may be changed directly through electronic control without resort to moving parts or expensive RF switches. The relatively fast plasma formation and extinction times ([/approx]10/ /mus) allow for rapid redirection of the microwave beam. An experimental system, dubbed the Agile Mirror, has been constructed using a cylindrical LexanTM vacuum chamber suspended within a water cooled Helmholtz coil pair capable of producing a uniform 500 Gauss field. Using this system we have created plasmas capable of reflecting 10 GHz microwaves with characteristics comparable to that of a plane metallic reflector. Most previous glow discharge work has concentrated either on the DC characteristics, or on the very early evolution (<1-2 μs), of the discharge. To create a practical agile mirror direction, we must be able to produce a stable, flat, homogeneous plasma sheet with predictable characteristics timescales from 5 μs to 1 ms-a regime where little pertinent quantitative data exists. This work concentrates on diagnosing the time resolved behavior of the agile mirror plasma during the mid-time, from t = 5-300 μs, in a regime which accentuates observed changes in the discharge circuit characteristics. Measurements on an air discharge produced using VD/approx2.2 kV, p ≈ 208 mTorr, and B ≈ 250 G reveal an ne=1011/ cm-3,/ Te=1[-]3 eV plasma with distinct negative glow, Faraday dark space, and positive column regions. Analysis of time resolved potential, temperature, and spectroscopic data reveal that this discharge transitions-on time scales of [/approx]100/ /mus-into a pure negative glow discharge. The characteristics and evolution of the discharge are highly reproducible. A computer model of the discharge reveals that heating of the background gas is responsible for the transition. Implications for operation of the agile mirror discharge as a plasma mirror are discussed.

Dietary saturated fat/cholesterol, but not unsaturated fat or starch, induces C-reactive protein associated early atherosclerosis and ectopic fat deposition in diabetic pigs

PubMed Central

2011-01-01

Background Diabetes is thought to accelerate cardiovascular disease depending on the type of diet. This study in diabetic subjects was performed to investigate the metabolic, inflammatory and cardiovascular effects of nutritional components typically present in a Western, Mediterranean or high glycaemic diet. Methods Streptozotocin-diabetic pigs (~45 kg) were fed for 10 weeks supplemental (40% of dietary energy) saturated fat/cholesterol (SFC), unsaturated fat (UF) or starch (S) in an eucaloric dietary intervention study. Results Fasting plasma total, LDL and HDL cholesterol concentrations were 3-5 fold higher (p < 0.01) in SFC compared to UF and S pigs. Fasting plasma NEFA concentrations (mmol/L) were highest (p < 0.05) in SFC (1.09 ± 0.17), intermediate in UF (0.80 ± 0.14) and lowest in S pigs (0.58 ± 0.14) whereas plasma glucose (~13 mmol/L), triglyceride (~0.5 mmol/L) and insulin (~24 pmol/L) concentrations were comparable among SFC, UF and S pigs. The postprandial response area under the curves (AUC, 0-4 h) for glucose but not for insulin and triglyceride responses were intermediate in SFC (617 ± 144) and lowest (p < 0.05) in UF (378 ± 157) compared to S pigs (925 ± 139). Fasting hepatic glucose production, hepatic and peripheral insulin sensitivity and blood pressure were not different among pigs. C-reactive protein (CRP) concentrations (mg/L) were highest (p < 0.05) in SFC (25 ± 4), intermediate in S (21 ± 3) and lowest in UF pigs (14 ± 2). Liver weights, liver and muscle triglyceride concentrations, and the surface area of aorta fatty streaks were highest (p < 0.01) in SFC pigs. A positive correlation between postprandial plasma CRP and aorta fatty streaks was observed in SFC pigs (R2 = 0.95). Retroperitoneal fat depot weight (g) was intermediate in SFC (260 ± 72), lowest in S (135 ± 51) and highest (p < 0.05) in UF (571 ± 95) pigs. Conclusion Dietary saturated fat/cholesterol induces inflammation, atherosclerosis and ectopic fat deposition whereas an equally high dietary unsaturated fat load does not induce these abnormalities and shows beneficial effects on postprandial glycaemia in diabetic pigs. PMID:21756316

Dietary saturated fat/cholesterol, but not unsaturated fat or starch, induces C-reactive protein associated early atherosclerosis and ectopic fat deposition in diabetic pigs.

PubMed

Koopmans, Sietse J; Dekker, Ruud; Ackermans, Mariette T; Sauerwein, Hans P; Serlie, Mireille J; van Beusekom, Heleen M M; van den Heuvel, Mieke; van der Giessen, Wim J

2011-07-14

Diabetes is thought to accelerate cardiovascular disease depending on the type of diet. This study in diabetic subjects was performed to investigate the metabolic, inflammatory and cardiovascular effects of nutritional components typically present in a Western, Mediterranean or high glycaemic diet. Streptozotocin-diabetic pigs (~45 kg) were fed for 10 weeks supplemental (40% of dietary energy) saturated fat/cholesterol (SFC), unsaturated fat (UF) or starch (S) in an eucaloric dietary intervention study. Fasting plasma total, LDL and HDL cholesterol concentrations were 3-5 fold higher (p < 0.01) in SFC compared to UF and S pigs. Fasting plasma NEFA concentrations (mmol/L) were highest (p < 0.05) in SFC (1.09 ± 0.17), intermediate in UF (0.80 ± 0.14) and lowest in S pigs (0.58 ± 0.14) whereas plasma glucose (~13 mmol/L), triglyceride (~0.5 mmol/L) and insulin (~24 pmol/L) concentrations were comparable among SFC, UF and S pigs. The postprandial response area under the curves (AUC, 0-4 h) for glucose but not for insulin and triglyceride responses were intermediate in SFC (617 ± 144) and lowest (p < 0.05) in UF (378 ± 157) compared to S pigs (925 ± 139). Fasting hepatic glucose production, hepatic and peripheral insulin sensitivity and blood pressure were not different among pigs. C-reactive protein (CRP) concentrations (mg/L) were highest (p < 0.05) in SFC (25 ± 4), intermediate in S (21 ± 3) and lowest in UF pigs (14 ± 2). Liver weights, liver and muscle triglyceride concentrations, and the surface area of aorta fatty streaks were highest (p < 0.01) in SFC pigs. A positive correlation between postprandial plasma CRP and aorta fatty streaks was observed in SFC pigs (R(2) = 0.95). Retroperitoneal fat depot weight (g) was intermediate in SFC (260 ± 72), lowest in S (135 ± 51) and highest (p < 0.05) in UF (571 ± 95) pigs. Dietary saturated fat/cholesterol induces inflammation, atherosclerosis and ectopic fat deposition whereas an equally high dietary unsaturated fat load does not induce these abnormalities and shows beneficial effects on postprandial glycaemia in diabetic pigs. © 2011 Koopmans et al; licensee BioMed Central Ltd.

Patients With Long-QT Syndrome Caused by Impaired hERG-Encoded Kv11.1 Potassium Channel Have Exaggerated Endocrine Pancreatic and Incretin Function Associated With Reactive Hypoglycemia

PubMed Central

Hyltén-Cavallius, Louise; Iepsen, Eva W.; Wewer Albrechtsen, Nicolai J.; Svendstrup, Mathilde; Lubberding, Anniek F.; Hartmann, Bolette; Jespersen, Thomas; Linneberg, Allan; Christiansen, Michael; Vestergaard, Henrik; Pedersen, Oluf; Holst, Jens J.; Kanters, Jørgen K.

2017-01-01

Background: Loss-of-function mutations in hERG (encoding the Kv11.1 voltage-gated potassium channel) cause long-QT syndrome type 2 (LQT2) because of prolonged cardiac repolarization. However, Kv11.1 is also present in pancreatic α and β cells and intestinal L and K cells, secreting glucagon, insulin, and the incretins glucagon-like peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide), respectively. These hormones are crucial for glucose regulation, and long-QT syndrome may cause disturbed glucose regulation. We measured secretion of these hormones and cardiac repolarization in response to glucose ingestion in LQT2 patients with functional mutations in hERG and matched healthy participants, testing the hypothesis that LQT2 patients have increased incretin and β-cell function and decreased α-cell function, and thus lower glucose levels. Methods: Eleven patients with LQT2 and 22 sex-, age-, and body mass index–matched control participants underwent a 6-hour 75-g oral glucose tolerance test with ECG recording and blood sampling for measurements of glucose, insulin, C-peptide, glucagon, GLP-1, and GIP. Results: In comparison with matched control participants, LQT2 patients had 56% to 78% increased serum insulin, serum C-peptide, plasma GLP-1, and plasma GIP responses (P=0.03–0.001) and decreased plasma glucose levels after glucose ingestion (P=0.02) with more symptoms of hypoglycemia (P=0.04). Sixty-three percent of LQT2 patients developed hypoglycemic plasma glucose levels (<70 mg/dL) versus 36% control participants (P=0.16), and 18% patients developed serious hypoglycemia (<50 mg/dL) versus none of the controls. LQT2 patients had defective glucagon responses to low glucose, P=0.008. β-Cell function (Insulin Secretion Sensitivity Index-2) was 2-fold higher in LQT2 patients than in controls (4398 [95% confidence interval, 2259–8562] versus 2156 [1961–3201], P=0.03). Pharmacological Kv11.1 blockade (dofetilide) in rats had similar effect, and small interfering RNA inhibition of hERG in β and L cells increased insulin and GLP-1 secretion up to 50%. Glucose ingestion caused cardiac repolarization disturbances with increased QTc intervals in both patients and controls, but with a 122% greater increase in QTcF interval in LQT2 patients (P=0.004). Conclusions: Besides a prolonged cardiac repolarization phase, LQT2 patients display increased GLP-1, GIP, and insulin secretion and defective glucagon secretion, causing decreased plasma glucose and thus increased risk of hypoglycemia. Furthermore, glucose ingestion increased QT interval and aggravated the cardiac repolarization disturbances in LQT2 patients. Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifier: NCT02775513. PMID:28235848

A comparison of plasma and prostate lycopene in response to typical servings of tomato soup, sauce or juice in men before prostatectomy.

PubMed

Grainger, Elizabeth M; Hadley, Craig W; Moran, Nancy E; Riedl, Kenneth M; Gong, Michael C; Pohar, Kamal; Schwartz, Steven J; Clinton, Steven K

2015-08-28

Tomato product consumption and estimated lycopene intake are hypothesised to reduce the risk of prostate cancer. To define the impact of typical servings of commercially available tomato products on resultant plasma and prostate lycopene concentrations, men scheduled to undergo prostatectomy (n 33) were randomised either to a lycopene-restricted control group ( < 5 mg lycopene/d) or to a tomato soup (2-2¾ cups prepared/d), tomato sauce (142-198 g/d or 5-7 ounces/d) or vegetable juice (325-488 ml/d or 11-16·5 fluid ounces/d) intervention providing 25-35 mg lycopene/d. Plasma and prostate carotenoid concentrations were measured by HPLC. Tomato soup, sauce and juice consumption significantly increased plasma lycopene concentration from 0·68 (sem 0·1) to 1·13 (sem 0·09) μmol/l (66 %), 0·48 (sem 0·09) to 0·82 (sem 0·12) μmol/l (71 %) and 0·49 (sem 0·12) to 0·78 (sem 0·1) μmol/l (59 %), respectively, while the controls consuming the lycopene-restricted diet showed a decline in plasma lycopene concentration from 0·55 (sem 0·60) to 0·42 (sem 0·07) μmol/l ( - 24 %). The end-of-study prostate lycopene concentration was 0·16 (sem 0·02) nmol/g in the controls, but was 3·5-, 3·6- and 2·2-fold higher in tomato soup (P= 0·001), sauce (P= 0·001) and juice (P= 0·165) consumers, respectively. Prostate lycopene concentration was moderately correlated with post-intervention plasma lycopene concentrations (r 0·60, P =0·001), indicating that additional factors have an impact on tissue concentrations. While the primary geometric lycopene isomer in tomato products was all-trans (80-90 %), plasma and prostate isomers were 47 and 80 % cis, respectively, demonstrating a shift towards cis accumulation. Consumption of typical servings of processed tomato products results in differing plasma and prostate lycopene concentrations. Factors including meal composition and genetics deserve further evaluation to determine their impacts on lycopene absorption and biodistribution.

Vitamin D deficiency is associated with severity of liver disease in HIV/HCV coinfected patients.

PubMed

Guzmán-Fulgencio, María; García-Álvarez, Mónica; Berenguer, Juan; Jiménez-Sousa, M Ángeles; Cosín, Jaime; Pineda-Tenor, Daniel; Carrero, Ana; Aldámiz, Teresa; Alvarez, Emilio; López, Juan Carlos; Resino, Salvador

2014-02-01

To study the association of plasma 25-hydroxy vitamin D (25(OH)D) levels in HIV/HCV coinfected patients with severity of liver disease and virological response to hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV). A cross-sectional study in 174 HIV/HCV coinfected patients that underwent a liver biopsy previously to start HCV therapy and a retrospective study of 125 of them. Plasma 25(OH)D levels were quantified by enzyme immunoassay. Liver biopsies were evaluated by METAVIR score. A sustained virological response (SVR) was defined as an undetectable serum HCV viral load (<10 IU/mL) up through 24 weeks after the end of HCV treatment. The median of plasma 25(OH)D level was 48 nmol/L (p25th: 32.5; p75th: 56.1) and 27 (15.5%) had 25(OH)D deficiency (<25 nmol/L). The percentage of 25(OH)D deficiency was higher in patients with significant fibrosis (F ≥ 2) (92.6% vs. 57.1%; p = 0.010) and moderate necroinflammatory activity grade (A ≥ 2) (85.2% vs. 60%; p = 0.043). However, adjusted logistic regression analyses showed that 25(OH)D deficiency was only associated with severity of liver disease [F ≥ 2 (OR = 8.47 (95% of confidence interval (CI) = 1.88; 38.3); p = 0.005) and A ≥ 2 (OR = 3.25 (95%CI = 1.06; 10.1); p = 0.040)]. Moreover, any significant relationship was found between 25(OH)D deficiency and SVR after HCV therapy. Plasma 25(OH)D deficiency was associated with liver disease severity in HIV/HCV coinfected patients, but it was not associated with HCV treatment failure. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

[Pharmacokinetics of (-)-clausenamide and its major metabolite 6-hydroxyl-clausenamide in beagle dogs by HPLC/MS].

PubMed

Song, Min; Qian, Wen; Hang, Tai-Jun; Zhang, Zheng-Xing

2005-10-01

To establish a sensitive and accurate method to study the pharmacokinetics of (-)-clausenamide [(-)-clau] and its major metabolite 6-hydroxyl-clausenamide (6-OH-clau) in the plasma of the Beagle dog. (-)-Clau was orally administered to six Beagle dogs at the dose of 30 mg x kg(-1), venous blood from front leg was sampled and plasma was separated for analysis. After extraction with ethyl acetate, the plasma samples were analyzed by HPLC/MS and the mobile phase was a mixture of methanol-water-acetic acid (60: 40: 0. 8) at the flow rate of 1.0 mL x min(-1). The API-ES positive ion SIM detection was carried out for the detection of both (-)-clau ([M + H] (+), m/z 298 ) and 6-OH-clau ([M + H - H2 O](+), m/z 296) with glipzide (glip) ([M + H](+), m/z 446) as internal standard. The pharmacokinetic parameters were calculated by 3P97 software. There was good linear relationship ( r > 0. 999) between the SIM responses and the concentrations for (-)-clau and 6-OH-clau at the range from 1.0 to 200 ng x mL(-1) and 0.2 to 40.0 ng x mL(-1), respectively. The absolute recovery was greater than 85%. The plasma concentration-time curves of (-)-clau and 6-OH-clau were both best fitted to a two-compartment model. The C(max) of (-)-clau and 6-OH-clau were (21 +/- 10) ng x mL(-1) and (3.9 +/- 2.2) ng x mL(-1), T(max) were (0.8 +/- 0.5) h and (1.3 +/- 0.5) h, T 1/2 alpha were (0.9 +/- 0.6) hand (1.4 +/- 0.6) h, T 1/2 beta were (19 +/- 23) hand (13 +/- 12) h, AUC(0-24 h) were (69 +/- 14) h x ng x mL(-1) and (12 +/- 7) h x ng x mL(-1) respectively. The established HPLC/MS method was sensitive and specific for the determination of (-)-clau. It was shown that the absorption and first phase elimination of (-)-clau were very quick in Beagle dogs, but the terminal elimination was very slow. The plasma concentration profile of its major metabolite 6-OH-clau was similar to (-)-clau and the AUC was relatively small in comparison with (-)-clau.

Does preoperative oral carbohydrate treatment reduce the postoperative surgical stress response in lumbar disc surgery?

PubMed

Dilmen, Ozlem Korkmaz; Yentur, Ercument; Tunali, Yusuf; Balci, Huriye; Bahar, Mois

2017-02-01

Surgical trauma produces metabolic and hormonal responses, which are characterized by insulin resistance. Due to extension of the preoperative fasting period, which increases the magnitude of postoperative insulin resistance, preoperative oral carbohydrates (POC) have been developed. This prospective, randomized, controlled study was performed on 43 ASA I-II patients undergoing elective microsurgical lumbar discectomy. The intervention group received oral carbohydrate solution 800mL the night before and 400mL 2h prior to operation. The other group fasted for 8h prior to operation. Blood samples were obtained the day before the operation, before induction of anesthesia, after skin incision, 1h, 2h, 6h and 24h following skin incision. Blood glucose, plasma insulin, cortisol and interleukin-6 (IL-6) levels were determined. The primary endpoint was to assess the effect of POC treatment on insulin resistance and surgical stress response following lumbar disc surgery. The secondary endpoint was to assess POC's effects on postoperative nausea and vomiting. The serum insulin levels were higher before induction of anesthesia in the study group and returned to fasted group levels by 2h after skin incision. The plasma IL-6 levels were higher in the intervention group at 6h after the skin incision. There were no differences between the two groups with respect to blood glucose, plasma cortisol levels and the incidence of nausea and vomiting. This study suggests that use of POC treatment does not attenuate development of insulin resistance in patients undergoing lumbar disc surgery. Copyright © 2016. Published by Elsevier B.V.

Effects of recombinant human prothrombin on thrombin generation in plasma from patients with hemophilia A and B.

PubMed

Hansson, K M; Gustafsson, D; Skärby, T; Frison, L; Berntorp, E

2015-07-01

The present study was carried out to investigate the impact of FII levels, and their increase, on the hemostatic potential in plasma from hemophilia A and B patients with and without inhibitors. Recombinant human factor (F) II (rhFII) was added ex vivo to plasma from 68 patients with hemophilia A and B, with or without inhibitors. The hemostatic potential as measured by thrombin generation (calibrated automated thrombogram [CAT]) was focused on the endogenous thrombin potential (ETP) as it has been shown to correlate with the clinical phenotype of bleeding in hemophilia patients and has also been used to guide bypassing therapy in hemophilia patients with inhibitors before elective surgery. The factor eight inhibitor bypassing agent (FEIBA(®) ) was used as a reference to the clinical situation. The study shows that rhFII concentration-dependently increased ETP by a similar magnitude in hemophilia A and B, both with and without inhibitors. Compared with FEIBA, rhFII showed a shallower concentration-response curve. In both types of hemophilia 100 mg L(-1) of rhFII roughly doubled the ETP. A corresponding response was obtained by 0.5 U mL(-1) of FEIBA. These data support the theory that FII is one of the major components responsible for the efficacy of FEIBA. The data also indicate that rhFII may be useful, alone or in combination with other coagulation factors, in some of the conditions for which FEIBA is used today, although more data are needed to substantiate this. © 2015 International Society on Thrombosis and Haemostasis.

Demonstration of the hollow channel plasma wakefield accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gessner, Spencer J.

2016-09-17

A plasma wakefield accelerator is a device that converts the energy of a relativistic particle beam into a large-amplitude wave in a plasma. The plasma wave, or wakefield, supports an enormous electricfield that is used to accelerate a trailing particle beam. The plasma wakefield accelerator can therefore be used as a transformer, transferring energy from a high-charge, low-energy particle beam into a high-energy, low-charge particle beam. This technique may lead to a new generation of ultra-compact, high-energy particle accelerators. The past decade has seen enormous progress in the field of plasma wakefield acceleration with experimental demonstrations of the acceleration ofmore » electron beams by several gigaelectron-volts. The acceleration of positron beams in plasma is more challenging, but also necessary for the creation of a high-energy electron-positron collider. Part of the challenge is that the plasma responds asymmetrically to electrons and positrons, leading to increased disruption of the positron beam. One solution to this problem, first proposed over twenty years ago, is to use a hollow channel plasma which symmetrizes the response of the plasma to beams of positive and negative charge, making it possible to accelerate positrons in plasma without disruption. In this thesis, we describe the theory relevant to our experiment and derive new results when needed. We discuss the development and implementation of special optical devices used to create long plasma channels. We demonstrate for the first time the generation of meter-scale plasma channels and the acceleration of positron beams therein.« less

Atmospheric nonequilibrium mini-plasma jet created by a 3D printer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takamatsu, Toshihiro, E-mail: toshihiro@plasma.es.titech.ac.jp; Tokyo Institute of Technology, Department of Energy Sciences, J2-32, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8502; Kawano, Hiroaki

2015-07-15

In this study, a small-sized plasma jet source with a 3.7 mm head diameter was created via a 3D printer. The jet’s emission properties and OH radical concentrations (generated by argon, helium, and nitrogen plasmas) were investigated using optical emission spectrometry (OES) and electron spin resonance (ESR). As such, for OES, each individual gas plasma propagates emission lines that derive from gases and ambient air inserted into the measurement system. For the case of ESR, a spin adduct of the OH radical is typically observed for all gas plasma treatment scenarios with a 10 s treatment by helium plasma generatingmore » the largest amount of OH radicals at 110 μM. Therefore, it was confirmed that a plasma jet source made by a 3D printer can generate stable plasmas using each of the aforementioned three gases.« less

Spectrometer Development in Support of Thomson Scattering Investigations for the Helicon Plasma Experiment (HPX)

NASA Astrophysics Data System (ADS)

Sandri, Eva; Davies, Richard; Azzari, Phil; Frank, John; Frank, Jackson; James, Royce; Hopson, Jordon; Duke-Tinson, Omar; Paolino, Richard; Sherman, Justin; Wright, Erin; Turk, Jeremy

2016-10-01

Now that reproducible plasmas have been created on the Helicon Plasma Experiment (HPX) at the Coast Guard Academy Plasma Laboratory (CGAPL), a high-performance spectrometer utilizing volume-phase-holographic (VPH) grating and a charge coupled device (CCD) camera with a range of 380-1090 nm and resolution of 1024x1024 is being assembled. This spectrometer will collect doppler shifted photons created by exciting the plasma with the first harmonic of a 2.5 J Nd:YAG laser at a wavelength of 1064 nm. Direct measurements of the plasma's temperature and density will be determined using HPX's Thomson Scattering (TS) system as a single spatial point diagnostic. TS has the capability of determining plasma properties on short time scales and will be used to create a robust picture of the internal plasma parameters. A prototype spectrometer has been constructed to explore the Andor CCD camera's resolution and sensitivity. Concurrently, through intensive study of the high energy TS system, safety protocols and standard operation procedures (SOP) for the Coast Guard's largest and most powerful Laser have been developed. The current status of the TS SOP, diagnostic development, and the collection optic's spectrometer will be reported. Supported by U.S. DEPS Grant [HEL-JTO] PRWJFY15-16.

Investigation of Recombination Processes In A Magnetized Plasma

NASA Technical Reports Server (NTRS)

Chavers, Greg; Chang-Diaz, Franklin; Rodgers, Stephen L. (Technical Monitor)

2002-01-01

Interplanetary travel requires propulsion systems that can provide high specific impulse (Isp), while also having sufficient thrust to rapidly accelerate large payloads. One such propulsion system is the Variable Specific Impulse Magneto-plasma Rocket (VASIMR), which creates, heats, and exhausts plasma to provide variable thrust and Isp, optimally meeting the mission requirements. A large fraction of the energy to create the plasma is frozen in the exhaust in the form of ionization energy. This loss mechanism is common to all electromagnetic plasma thrusters and has an impact on their efficiency. When the device operates at high Isp, where the exhaust kinetic energy is high compared to the ionization energy, the frozen flow component is of little consequence; however, at low Isp, the effect of the frozen flow may be important. If some of this energy could be recovered through recombination processes, and re-injected as neutral kinetic energy, the efficiency of VASIMR, in its low Isp/high thrust mode may be improved. In this operating regime, the ionization energy is a large portion of the total plasma energy. An experiment is being conducted to investigate the possibility of recovering some of the energy used to create the plasma. This presentation will cover the progress and status of the experiment involving surface recombination of the plasma.

The Colorado Solar Wind Experiment

NASA Astrophysics Data System (ADS)

Munsat, Tobin; Han, Jia; Horanyi, Mihaly; Ulibarri, Zach; Wang, Xu; Yeo, Lihsia

2016-10-01

The Colorado Solar Wind Experiment (CSWE) is a new device developed at the Institute for Modeling Plasma, Atmospheres, and Cosmic Dust (IMPACT) at the University of Colorado. This large ion source is for studies of the interaction of solar wind plasma with planetary surfaces and cosmic dust, and for the investigation of plasma wake physics. With a plasma beam diameter of 12 cm at the source, ion energies of up to 1 keV, and ion flows of up to 1 mA/cm2, a large cross-section Kaufman Ion Source is used to create steady state plasma flow to model the solar wind in an experimental vacuum chamber. Chamber pressure can be reduced to 3e-5 Torr under operating conditions to suppress ion-neutral collisions and create a uniform ion velocity distribution. Diagnostic instruments such as a double Langmuir probe and an ion energy analyzer are mounted on a two-dimensional translation stage that allow the beam to be characterized throughout the chamber. Early experiments include the measurement of dust grain charging from the interaction with flowing plasma, and measurements of the plasma sheath created by the interaction of the flowing plasma impinging on a surface with a dipole magnetic field. This poster will describe the facility and the scientific results obtained to date.

Low-Renin Hypertension With Relative Aldosterone Excess Is Associated With Impaired NO-Mediated Vasodilation

PubMed Central

Duffy, Stephen J.; Biegelsen, Elizabeth S.; Eberhardt, Robert T.; Kahn, David F.; Kingwell, Bronwyn A.; Vita, Joseph A.

2009-01-01

Recent studies suggest that hypertension associated with low renin status and hyperaldosteronism is associated with increased risk for end-organ damage and cardiovascular events compared with other forms of hypertension. Additionally, experimental studies have demonstrated impaired nitric oxide-mediated bioactivity in these states. To investigate the relation between renin/aldosterone status and resistance vessel function, we examined plasma renin activity, serum aldosterone level, and forearm blood flow responses to the endothelium-dependent vasodilator methacholine and the endothelium-independent vasodilators sodium nitroprusside and verapamil using venous occlusion plethysmography in 130 volunteers (43 hypertensive, 87 normotensive). Low renin status was associated with impaired responses to methacholine and nitroprusside in patients with hypertension. Peak methacholine response was 8.7±5.6 mL/min per dL in the lowest renin quartile (0.1 to 0.3 ng/mL per hour) versus 14.3±7.3 mL/min per dL in the highest 3 renin quartiles combined (0.4 to 4.6 ng/mL per hour; P<0.001). Peak nitroprusside response was 5.6±2.3 mL/min per dL in the lowest renin quartile versus 13.3±4.1 mL/min per dL in the highest 3 renin quartiles combined (P<0.001). Blood pressure and other clinical characteristics were similar in all 4 quartiles. Vasodilator responses to verapamil did not relate to renin activity. Methacholine and nitroprusside responses did not relate to renin status in normotensive controls (P=0.34). Importantly, hypertensive patients with a high aldosterone/renin ratio also had impaired responses to methacholine. This study demonstrates that low-renin hypertension is associated with marked impairment of nitric oxide-mediated vasodilation of resistance vessels in the forearm vasculature of humans. This impairment could contribute to adverse outcomes in patients with low-renin hypertension and relative aldosterone excess. PMID:16172426

Effects of Mood Inductions by Meal Ambiance and Moderate Alcohol Consumption on Endocannabinoids and N-Acylethanolamines in Humans: A Randomized Crossover Trial

PubMed Central

Schrieks, Ilse C.; Ripken, Dina; Stafleu, Annette; Witkamp, Renger F.; Hendriks, Henk F. J.

2015-01-01

Background The endocannabinoid system is suggested to play a regulatory role in mood. However, the response of circulating endocannabinoids (ECs) to mood changes has never been tested in humans. In the present study, we examined the effects of mood changes induced by ambiance and moderate alcohol consumption on plasma ECs 2-arachidonoylglycerol (2-AG), anandamide (AEA), and some N-acylethanolamine (NAE) congeners in humans. Methods Healthy women (n = 28) participated in a randomized cross-over study. They consumed sparkling white wine (340 mL; 30 g alcohol) or alcohol-free sparkling white wine (340 mL; <2 g alcohol) as part of a standard evening meal in a room with either a pleasant or an unpleasant ambiance. Results Plasma concentrations of palmitoylethanolamide (PEA) and stearoylethanolamide (SEA) increased after 30 min in the unpleasant ambiance, while they decreased in the pleasant ambiance. Changes in ECs and their NAE congeners correlated with mood states, such as happiness and fatigue, but in the pleasant ambiance without alcohol only. ECs and their NAE congeners were correlated with serum free fatty acids and cortisol. Conclusion This is the first human study to demonstrate that plasma NAEs are responsive to an unpleasant meal ambiance. Furthermore, associations between mood states and ECs and their NAE congeners were observed. Trial Registration Clinicaltrials.gov NCT01426022 PMID:25962070

Generation of action potentials in a mathematical model of corticotrophs.

PubMed Central

LeBeau, A P; Robson, A B; McKinnon, A E; Donald, R A; Sneyd, J

1997-01-01

Corticotropin-releasing hormone (CRH) is an important regulator of adrenocorticotropin (ACTH) secretion from pituitary corticotroph cells. The intracellular signaling system that underlies this process involves modulation of voltage-sensitive Ca2+ channel activity, which leads to the generation of Ca2+ action potentials and influx of Ca2+. However, the mechanisms by which Ca2+ channel activity is modulated in corticotrophs are not currently known. We investigated this process in a Hodgkin-Huxley-type mathematical model of corticotroph plasma membrane electrical responses. We found that an increase in the L-type Ca2+ current was sufficient to generate action potentials from a previously resting state of the model. The increase in the L-type current could be elicited by either a shift in the voltage dependence of the current toward more negative potentials, or by an increase in the conductance of the current. Although either of these mechanisms is potentially responsible for the generation of action potentials, previous experimental evidence favors the former mechanism, with the magnitude of the shift required being consistent with the experimental findings. The model also shows that the T-type Ca2+ current plays a role in setting the excitability of the plasma membrane, but does not appear to contribute in a dynamic manner to action potential generation. Inhibition of a K+ conductance that is active at rest also affects the excitability of the plasma membrane. PMID:9284294

The role of the large scale convection electric field in erosion of the plasmasphere during moderate and strong storms

NASA Astrophysics Data System (ADS)

Thaller, S. A.; Wygant, J. R.; Cattell, C. A.; Breneman, A. W.; Bonnell, J. W.; Kletzing, C.; De Pascuale, S.; Kurth, W. S.; Hospodarsky, G. B.; Bounds, S. R.

2015-12-01

The Van Allen Probes offer the first opportunity to investigate the response of the plasmasphere to the enhancement and penetration of the large scale duskward convection electric field in different magnetic local time (MLT) sectors. Using electric field measurements and estimates of the cold plasma density from the Van Allen Probes' Electric Fields and Waves (EFW) instrument, we study erosion of the plasmasphere during moderate and strong geomagnetic storms. We present the electric field and density data both on an orbit by orbit basis and synoptically, showing the behavior of the convection electric field and plasmasphere over a period of months. The data indicate that the large scale duskward electric field penetrates deep (L shell < 3) into the inner magnetosphere on both the dusk and dawn sides, but that the plasmasphere response on the dusk and dawn sides differ. In particular, significant (~2 orders of magnitude) decreases in the cold plasma density occur on the dawn side within hours of the onset of enhanced duskward electric field. In contrast, on the dusk side, the plasmapause is located at higher L shell than it is on the dawn side. In some cases, in the post-noon sector, cold plasma density enhancements accompany duskward electric field enhancements for the first orbit after the electric field enchantment, consistent with a duskside, sunward flowing, drainage plume.

Attachment of Poly(l-lactide) Nanoparticles to Plasma-Treated Non-Woven Polymer Fabrics Using Inkjet Printing.

PubMed

Ivanova, Tatiana V; Baier, Grit; Landfester, Katharina; Musin, Eduard; Al-Bataineh, Sameer A; Cameron, David C; Homola, Tomáš; Whittle, Jason D; Sillanpää, Mika

2015-09-01

Active dressings that based on fabric materials are an area of interest for the treatment of wounds. Poly(l-lactide) nanoparticles containing the antimicrobial agent octenidine can be controllably lysed by toxins released by pathogenic bacteria thus releasing antimicrobial material in response to the presence of the bacterial toxins and so counteracting the infection. We developed an integrated engineering solution that allows for the stable immobilisation of nanoparticles on non-woven fabrics. The process involves coating nanoparticles on non-woven polymer surfaces by using an inkjet printing process. In order to improve the adhesion and retention of the nanoparticles on the fabric, surface pretreatment of the non-woven fabric using plasma jet treatment can be applied to increase its surface energy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Plasma chemistry reference values in ostriches.

PubMed

Verstappen, F A L M; Lumeij, J T; Bronneberg, R G G

2002-01-01

Reference values for 18 plasma chemical variables in blue neck ostriches (Struthio camelus australis, n = 60, age 24-36 mo) were established for use in veterinary clinical practice using nonparametric statistics. The following values were established for the percentiles P2.5 and P97.5: sodium 147-157 mmol/L, calcium 2.4-4.8 mmol/L, inorganic phosphate 1.3-2.3 mmol/L, chloride 94-105 mmol/L, glucose 10.3-13.7 mmol/L, urea 0.5-0.8 mmol/L, uric acid 351-649 mumol/L, bile acids 8-33 mumol/L, total protein 39-56 g/L, albumin-globulin ratio 0.45-0.59, osmolality 304-330 mOsm/kg, alkaline phosphate 69-217 IU/L, aspartate aminotransferase 243-418 IU/L, gamma-glutamyltransferase 0-1 IU/L, creatine kinase 1648-4894 IU/L, glutamate dehydrogenase 8-17 IU/L, and lactate dehydrogenase 860-2236 IU/L. The plasma calcium concentration was significantly (P < 0.001; r = 0.74) related to the total protein concentration and an adjustment-formula for calcium was derived: adjusted Ca (mmol/L) = Ca (mmol/L)--0.09 TP (g/L) + 4.4. The influence of blood sample treatment on the plasma potassium concentration as seen in other avian species was demonstrated in a separate experiment, emphasizing the need to separate plasma and cells immediately after collection in avian blood samples.

Pharmacodynamics of norepinephrine reuptake inhibition: Modeling the peripheral and central effects of atomoxetine, duloxetine, and edivoxetine on the biomarker 3,4-dihydroxyphenylglycol in humans.

PubMed

Kielbasa, William; Lobo, Evelyn

2015-12-01

Norepinephrine, a neurotransmitter in the autonomic sympathetic nervous system, is deaminated by monoamine oxidase to 3,4-dihydroxyphenylglycol (DHPG). Inhibition of the NE transporter (NET) using DHPG as a biomarker was evaluated using atomoxetine, duloxetine, and edivoxetine as probe NET inhibitors. Pharmacokinetic and pharmacodynamic data were obtained from healthy subjects (n = 160) from 5 clinical trials. An indirect response model was used to describe the relationship between drug plasma concentration and DHPG concentration in plasma and cerebrospinal fluid (CSF). The baseline plasma DHPG concentration (1130-1240 ng/mL) and Imax (33%-37%) were similar for the 3 drugs. The unbound plasma drug IC50 (IC50U ) based on plasma DHPG was 0.973 nM for duloxetine, 0.136 nM for atomoxetine, and 0.041 nM for edivoxetine. The baseline CSF DHPG concentration (1850-2260 ng/mL) was similar for the 3 drugs, but unlike plasma DHPG, the Imax for DHPG was 38% for duloxetine, 53% for atomoxetine, and75% for edivoxetine. The IC50U based on CSF DHPG was 2.72 nM for atomoxetine, 1.22 nM for duloxetine, and 0.794 nM for edivoxetine. These modeling results provide insights into the pharmacology of NET inhibitors and the use of DHPG as a biomarker. © 2015, The American College of Clinical Pharmacology.

Plasma chitinase 3-like 1 is persistently elevated during first month after minimally invasive colorectal cancer resection.

PubMed

Shantha Kumara, H M C; Gaita, David; Miyagaki, Hiromichi; Yan, Xiaohong; Hearth, Sonali Ac; Njoh, Linda; Cekic, Vesna; Whelan, Richard L

2016-08-15

To assess blood chitinase 3-like 1 (CHi3L1) levels for 2 mo after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC). CRC patients in an Institutional Review Board approved data/plasma bank who underwent elective MICR for whom preoperative (PreOp), early postoperative (PostOp), and 1 or more late PostOp samples [postoperative day (POD) 7-27] available were included. Plasma CHi3L1 levels (ng/mL) were determined in duplicate by enzyme linked immunosorbent assay. PreOp and PostOp plasma sample were available for 80 MICR cancer patients for the study. The median PreOp CHi3L1 level was 56.8 CI: 41.9-78.6 ng/mL (n = 80). Significantly elevated (P < 0.001) median plasma levels (ng/mL) over PreOp levels were detected on POD1 (667.7 CI: 495.7, 771.7; n = 79), POD 3 (132.6 CI: 95.5, 173.7; n = 76), POD7-13 (96.4 CI: 67.7, 136.9; n = 62), POD14-20 (101.4 CI: 80.7, 287.4; n = 22), and POD 21-27 (98.1 CI: 66.8, 137.4; n = 20, P = 0.001). No significant difference in plasma levels were noted on POD27-41. Plasma CHi3L1 levels were significantly elevated for one month after MICR. Persistently elevated plasma CHi3L1 may support the growth of residual tumor and metastasis.

Increasing the Vegetable Intake Dose Is Associated with a Rise in Plasma Carotenoids without Modifying Oxidative Stress or Inflammation in Overweight or Obese Postmenopausal Women123

PubMed Central

Crane, Tracy E.; Kubota, Chieri; West, Julie L.; Kroggel, Mark A.; Wertheim, Betsy C.; Thomson, Cynthia A.

2011-01-01

The optimal amount of vegetable consumption required to reduce chronic disease risk is widely debated. Intervention trials evaluating biological activity of vegetables at various doses are limited. We conducted a 3-dose, crossover feeding trial to test the hypothesis that vegetable intake is associated in a dose-dependent manner with increased plasma carotenoids and subsequently reduced oxidative stress and inflammation in 49 overweight, postmenopausal women. Participants were assigned in random order to 2 (130 g), 5 (287 g), and 10 (614 g) daily servings of fresh, greenhouse-grown vegetables for 3-wk intervals with a 4-wk washout period between treatments. Plasma total carotenoids significantly increased from 1.63 to 2.07 μmol/L with a dose of 2 vegetable servings, from 1.49 to 2.84 μmol/L with a dose of 5 vegetable servings, and from 1.40 to 4.42 μmol/L with a dose of 10 vegetable servings (pre-post paired ttests, all P < 0.001). The change during each feeding period increased with each dose level (P < 0.001). Urine concentrations of 8-isoprostane F2α, hexanoyl lysine, and serum high sensitivity C-reactive protein were not affected by any administered vegetable dose. In this variable-dose vegetable study, a dose-response for plasma carotenoids was demonstrated without significant change in oxidative stress and inflammation in overweight, postmenopausal women. PMID:21865569

Urinary and plasma purine derivatives in fed and fasted llamas (Lama glama and L. guanacoe).

PubMed

Bakker, M L; Chen, X B; Kyle, D J; Orskov, E R; Bourke, D A

1996-02-01

The changes in urinary and plasma purine derivatives in response to fasting and level of feeding in llamas were examines. In one experiment, four llamas were gradually deprived of feed within 3 days and then fasted for 6 days. Daily urinary excretion of purine derivatives decreased with feed intake and leveled on the last 3 days of fasting at 177 +/- 26 mumol/kg W0.75. Allantoin and uric acid comprised 71% and 15% of total purine derivatives, respectively, in both fed and fasted states, but hypoxanthine plus xanthine increased from 9% to 36%. Plasma concentration of allantoin declined with feed intake reduction, but those of uric acid (217 mumol/l) and hypoxanthine plus xanthine (27 mumol/l) remained relatively unchanged. Concentration of uric acid was higher than that of allantoin, probably due to a high reabsorption of uric acid in renal tubules, which was measured as over 90%. In a second experiment, the four llamas were fed at 860 and 1740 g dry matter/d in a crossover design. Urinary total purine derivatives excretion responded to feed intake (10.4 vs 14.4 mmol/d), although the observed differences did not reach significance. Compared with some ruminant species, it appears that the llama resembles sheep regarding the magnitude of urinary purine derivatives excretion but is unique in maintaining a high concentration of uric acid in plasma, which could be part of the llama's adaptation to their environment.

Acute depletion of plasma glutamine increases leucine oxidation in prednisone-treated humans

PubMed Central

Le Bacquer, Olivier; Mauras, Nelly; Welch, Susan; Haymond, Morey; Darmaun, Dominique

2007-01-01

Background, aims & methods To determine whether depletion in plasma glutamine worsens the catabolic response to corticosteroids, 7 healthy volunteers received oral prednisone for 6 days on 2 separate occasions, at least 2 weeks apart, and in random order. On the 6th day of each treatment course, they received 5h intravenous infusions of L-[1-14C]-leucine and L-[1-13C]-glutamine in the postabsorptive state 1) under baseline conditions (prednisone only day), and 2) after 24h of treatment with phenylbutyrate (prednisone+phenylbutyrate day), a glutamine chelating agent. Results Phenylbutyrate treatment was associated with 1) an ≈15% decline in plasma glutamine concentration (627±39 vs. 530±31 μmol.L-1; P<0.05), 2) no change in leucine appearance rate, an index of protein breakdown (124±9 vs. 128±9 μmol.kg-1.h-1; NS) nor in non oxidative leucine disposal, an index of whole body protein synthesis (94±9 vs. 91±7 μmol.kg -1.h-1; NS); and 3) a ≈25% rise in leucine oxidation (30±1 vs. 38±2 μmol.kg-1.h-1, P<0.05), despite an ≈25% decline (p<0.05) in leucine concentration. Conclusions In a model of mild, stress-induced protein catabolism, depletion of plasma glutamine per se may worsen branched chain amino acid and protein wasting. PMID:17097772

Hydroxytyrosol disposition in humans.

PubMed

Miro-Casas, Elisabet; Covas, Maria-Isabel; Farre, Magi; Fito, Montserrat; Ortuño, Jordi; Weinbrenner, Tanja; Roset, Pere; de la Torre, Rafael

2003-06-01

Animal and in vitro studies suggest that phenolic compounds in virgin olive oil are effective antioxidants. In animal and in vitro studies, hydroxytyrosol and its metabolites have been shown to be strong antioxidants. One of the prerequisites to assess their in vivo physiologic significance is to determine their presence in human plasma. We developed an analytical method for both hydroxytyrosol and 3-O-methyl-hydroxytyrosol in plasma. The administered dose of phenolic compounds was estimated from methanolic extracts of virgin olive oil after subjecting them to different hydrolytic treatments. Plasma and urine samples were collected from 0 to 12 h before and after 25 mL of virgin olive oil intake, a dose close to that used as daily intake in Mediterranean countries. Samples were analyzed by capillary gas chromatography-mass spectrometry before and after being subjected to acidic and enzymatic hydrolytic treatments. Calibration curves were linear (r >0.99). Analytical recoveries were 42-60%. Limits of quantification were <1.5 mg/L. Plasma hydroxytyrosol and 3-O-methyl-hydroxytyrosol increased as a response to virgin olive oil administration, reaching maximum concentrations at 32 and 53 min, respectively (P <0.001 for quadratic trend). The estimated hydroxytyrosol elimination half-life was 2.43 h. Free forms of these phenolic compounds were not detected in plasma samples. The proposed analytical method permits quantification of hydroxytyrosol and 3-O-methyl-hydroxytyrosol in plasma after real-life doses of virgin olive oil. From our results, approximately 98% of hydroxytyrosol appears to be present in plasma and urine in conjugated forms, mainly glucuronoconjugates, suggesting extensive first-pass intestinal/hepatic metabolism of the ingested hydroxytyrosol.

Hypertrophic Scars: Are Vitamins and Inflammatory Biomarkers Related with the Pathophysiology of Wound Healing?

PubMed

Correia-Sá, Inês; Serrão, Paula; Marques, Marisa; Vieira-Coelho, Maria A

2017-12-01

Hypertrophic scars are a consequence of wound healing. The objective of the present study is to evaluate vitamin D and inflammatory biomarker plasma levels during wound healing. A prospective study was performed in patients (n = 63) submitted to body contouring surgery. Blood samples were collected before (t 0 ) and 5 days after surgery (t 5 ). Blood cell count, protein inflammatory biomarkers, and circulating plasma levels of 25(OH)D, vitamin A and vitamin E were quantified. Six months after surgery, scars were evaluated and classified as normal or hypertrophic. At the end of the study, 73% of the patients developed a normal scar (control group, n = 46) and 27% of the patients presented hypertrophic scars (HT group, n = 17). The patients in the HT group presented higher eosinophil (0.145 × 10 9 /L vs. 0.104 × 10 9 /L, p = 0.028) and basophil count (0.031 × 10 9 /L vs. 0.22 × 10 9 /L, p = 0.049) and C-reactive protein levels (6.12 mg/L vs. 2.30 mg/L, p = 0.015) in t 0 than the patients in the control group. At t 5 , the patients in the HT group showed a decrease in neutrophil (3.144 × 10 9/L vs. 4.03 × 10 9 /L, p = 0.031) and an increase in basophil (0.024 × 10 9 /L vs. 0.015 × 10 9 /L, p = 0.005) and lymphocyte count (1.836 × 10 9 /L vs. 1.557 × 10 9 /L; p = 0.028). Before surgery, vitamin D plasma levels were found to be decreased by almost 50% (23.52 ng/mL vs. 15.46 ng/mL, p = 0.031) in the patients who developed hypertrophic scars. Thirty-one percent of the patients submitted to bariatric surgery had more hypertrophic scars, versus 24% of the patients with no previous bariatric surgery. There is a different systemic inflammatory profile response in the patients during the formation of hypertrophic scars. Vitamin D plasma levels are marked reduced in these patients. Considering the powerful anti-inflammatory effect of vitamin D, these findings could be related.

Seated saline suppression testing for the diagnosis of primary aldosteronism: a preliminary study.

PubMed

Ahmed, Ashraf H; Cowley, Diane; Wolley, Martin; Gordon, Richard D; Xu, Shengxin; Taylor, Paul J; Stowasser, Michael

2014-08-01

Failure of aldosterone suppression by sodium loading during fludrocortisone suppression testing (FST) or saline suppression testing (SST) confirms primary aldosteronism (PA). We previously found recumbent SST (RSST) to lack sensitivity. Aldosterone levels can be higher upright (e.g. seated) than recumbent in patients with PA and upright levels are used during FST. We therefore hypothesized that seated SST (SSST) is more sensitive than RSST, especially for posture-responsive PA. Of 66 patients who underwent FST (upright plasma aldosterone levels measured at 10am basally and after 4 days fludrocortisone 0.1 mg 6-hourly and oral salt loading), 31 underwent SST (aldosterone levels measured basally at 8am and after infusion of 2 L normal saline over 4h) both recumbent and seated in randomized order and at least 2 weeks apart. FST confirmed PA in 23 of 31 patients (day 4 upright aldosterone level >165 pmol/L), excluded PA in three and was originally "inconclusive" in five. However, one with "inconclusive" FST had PA confirmed by lateralizing AVS and was reclassified "unilateral PA". Of 24 with confirmed PA (eight unilateral, 11 bilateral, and five undetermined subtype), 23 (96%) tested positive by SSST (4-h aldosterone level >165 pmol/L) compared with 8 (33%) by RSST (4-h plasma aldosterone level >140 pmol/L) (P < .001). RSST missed one unilateral, all bilateral, and four with as-yet undetermined subtype. RSST was positive in 7 of 10 (70%) posture-unresponsive vs one of 14 (7.1%) posture-responsive patients (P < .005). These preliminary results suggest that seated SST may be superior to recumbent SST in terms of sensitivity for detecting PA, especially posture-responsive forms, and may represent a reliable alternative to FST.

Randomised trial of the bioavailability and efficacy of orally administered flunixin, carprofen and ketoprofen in a pain model in sheep.

PubMed

Marini, D; Pippia, J; Colditz, I G; Hinch, G; Petherick, J C; Lee, C

2015-08-01

To determine the efficacy and bioavailability of non-steroidal anti-inflammatory drugs (NSAIDs) when administered orally to sheep. Randomised experimental design with four treatment groups: three NSAID groups and one control group (n = 10/group). The study animals were 40 18-month-old Merino ewes with an average weight of 31.4 ± 0.5 kg. Treatment was given orally at 24 h intervals for 6 days at dose rates expected to achieve therapeutic levels in sheep: carprofen (8.0 mg/kg), ketoprofen (8.0 mg/kg) and flunixin (4.0 mg/kg). Oil of turpentine (0.1 mL) was injected into a forelimb of each sheep to induce inflammation and pain; responses (force plate pressure, skin temperature, limb circumference, haematology and plasma cortisol) were measured at 0, 3, 6, 9, 12, 24, 36, 48, 72 and 96 h post-injection. NSAID concentrations were determined by ultra-high-pressure liquid chromatography. The NSAIDs were detectable in ovine plasma 2 h after oral administration, with average concentrations of 4.5-8.4 µg/mL for ketoprofen, 2.6-4.1 µg/mL for flunixin and 30-80 µg/mL for carprofen. NSAID concentrations dropped 24 h after administration. Pain response to an oil of turpentine injection was assessed using the measures applied but no effect of the NSAIDs was observed. Although this pain model has been previously validated, the responses observed in this study differed from those in the previous study. The three NSAIDs reached inferred therapeutic concentrations in blood at 2 h after oral administration. The oil of turpentine lameness model may need further validation. © 2015 Australian Veterinary Association.

Experimental investigation of standing wave effect in dual-frequency capacitively coupled argon discharges: role of a low-frequency source

NASA Astrophysics Data System (ADS)

Zhao, Kai; Liu, Yong-Xin; Kawamura, E.; Wen, De-Qi; Lieberman, M. A.; Wang, You-Nian

2018-05-01

It is well known that the plasma non-uniformity caused by the standing wave effect has brought about great challenges for plasma material processing. To improve the plasma uniformity, a low-frequency (LF) power source is introduced into a 100 MHz very-high-frequency (VHF) capacitively coupled argon plasma reactor. The effect of the LF parameters (LF voltage amplitude ϕ L and LF source f L) on the radial profile of plasma density has been investigated by utilizing a hairpin probe. The result at a low pressure (1 Pa) is compared to the one obtained by a 2D fluid-analytical capacitively coupled plasma model, showing good agreement in the plasma density radial profile. The experimental results show that the plasma density profile exhibits different dependences on ϕ L and f L at different gas pressures/electrode driven types (i.e., the two rf sources are applied on one electrode (case I) and separate electrodes (case II)). At low pressures (e.g., 8 Pa), the pronounced standing wave effect revealed in a VHF discharge can be suppressed at a relatively high ϕ L or a low f L in case I, because the HF sheath heating is largely weakened due to strong modulation by the LF source. By contrast, ϕ L and f L play insignificant roles in suppressing the standing wave effect in case II. At high pressures (e.g., 20 Pa), the opposite is true. The plasma density radial profile is more sensitive to ϕ L and f L in case II than in case I. In case II, the standing wave effect is surprisingly enhanced with increasing ϕ L at higher pressures; however, the center-high density profile caused by the standing wave effect can be compensated by increasing f L due to the enhanced electrostatic edge effect dominated by the LF source. In contrast, the density radial profile shows a much weaker dependence on ϕ L and f L in case I at higher pressures. To understand the different roles of ϕ L and f L, the electron excitation dynamics in each case are analyzed based on the measured spatio-temporal distributions of the electron-impact excitation rate by phase resolved optical emission spectroscopy.

Proteomic plasma profile of psoriatic patients.

PubMed

Gęgotek, Agnieszka; Domingues, Pedro; Wroński, Adam; Wójcik, Piotr; Skrzydlewska, Elżbieta

2018-06-05

Psoriasis is a chronic, immune-mediated inflammatory skin disease with severe consequences for the whole organism. The lack of complete knowledge of the main factors predisposing an individual to the appearance of psoriatic lesions, has recently led to the search for modifications in biochemical pathways participating in the development of this disease. We therefore aimed to investigate changes in the plasma proteomic profile of patients with psoriasis. A proteomics approach was used to analyze the expression of proteins in plasma from psoriatic patients and healthy controls (sex- and age-matched individuals). The analysis was performed using gel electrophoresis, followed by nanoflow LC-MS/MS using a Q-Exactive OrbiTrap mass spectrometer. Proteomic data indicated a significant decrease in the level of proteins involved in lipid metabolism, such as apolipoprotein M, and proteins involved in the management of vitamin D levels in psoriatic patients' plasma. These changes were accompanied by the expression of proteins involved in immune response and signal transduction. This was particularly evident by the level of transcriptional factors, including AT motif binding factor 1, which regulates excessive cellular proliferation and differentiation. It was also suggested that psoriasis development was associated with increased expression of proteins directly involved in signaling molecule secretion [biotinidase and BAI1-associated protein 3]. In addition, the lipid peroxidation product - 4-hydroxynonenal (4-HNE) generates higher level of adducts with proteins in the plasma of psoriatic patients. Moreover, plasma proteins from healthy subjects creating with 4-HNE adducts were mainly characterized as structural, while in the plasma of psoriatic patients, increased levels of 4-HNE-protein adducts with catalytic activity were observed. The results presented herein confirm the current knowledge about the profile of proteins responsible for the immune response and management of vitamin D in the plasma of psoriatic patients. However, several new proteins were also identified, which are involved in signal transduction and lipid metabolism as well as catalytic activity. The expression or structure of these proteins was shown to change through the course of the development of psoriasis. This knowledge may help contribute to the design of more specific pharmacotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Plasma lactate concentration as a predictor of gastric necrosis and survival among dogs with gastric dilatation-volvulus: 102 cases (1995-1998).

PubMed

de Papp, E; Drobatz, K J; Hughes, D

1999-07-01

To determine relationships between plasma lactate concentration and gastric necrosis and between plasma lactate concentration and outcome for dogs with gastric dilatation-volvulus. Retrospective study. 102 dogs. Information on signalment, history, plasma lactate concentration, medical and surgical treatment, cost of hospitalization, and outcome was retrieved from medical records. 69 of 70 (99%) dogs with plasma lactate concentration < 6.0 mmol/L survived, compared with 18 of 31 (58%) dogs with plasma lactate concentration > 6.0 mmol/L (1 dog euthanatized for economic reasons was not included). Gastric necrosis was identified in 38 (37%) dogs. Median plasma lactate concentration in dogs with gastric necrosis (6.6 mmol/L) was significantly higher than concentration in dogs without gastric necrosis (3.3 mmol/L). Specificity and sensitivity of using plasma lactate concentration (with a cutoff of 6.0 mmol/L) to predict which dogs had gastric necrosis were 88 and 61%, respectively. Sixty-two of 63 (98%) dogs without gastric necrosis survived, compared with 25 of 38 (66%) dogs with gastric necrosis. Preoperative plasma lactate concentration was a good predictor of gastric necrosis and outcome for dogs with GDV. Preoperative measurement of plasma lactate concentration may assist in determining prognosis of dogs with GDV.

Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans.

PubMed

Verhoef, Petra; Pasman, Wilrike J; Van Vliet, Trinette; Urgert, Rob; Katan, Martijn B

2002-12-01

A high plasma total homocysteine concentration is associated with increased risk of cardiovascular disease. Consumption of unfiltered or filtered coffee raises total homocysteine concentrations in healthy volunteers. The responsible compound, however, is unknown. The objective was to determine whether caffeine explains the homocysteine-raising effect of coffee. Forty-eight subjects aged 19-65 y completed this randomized crossover study with 3 treatments, each lasting 2 wk. Subjects consumed 6 capsules providing 870 mg caffeine/d (test treatment), 0.9 L paper-filtered coffee providing approximately 870 mg caffeine/d, or 6 placebo capsules. Blood samples were drawn fasting and 4 h after consumption of 0.45 L coffee or 3 capsules. The mean fasting plasma homocysteine concentration after the placebo treatment was 9.6 +/- 3.1 micro mol/L. The caffeine and coffee treatments increased fasting homocysteine by 0.4 micro mol/L (95% CI: 0.1, 0.7; P = 0.04), or 5%, and by 0.9 micro mol/L (95% CI: 0.6, 1.2; P = 0.0001), or 11%, respectively, compared with placebo. The increase in homocysteine concentrations 4 h after consumption of 0.45 L coffee relative to consumption of 3 placebo capsules was 19% (P = 0.0001). Caffeine treatment had a much weaker acute effect on homocysteine (4%; P = 0.09). Effects of caffeine were stronger in women than in men, but the effects of coffee did not differ significantly between men and women. Caffeine is partly responsible for the homocysteine-raising effect of coffee. Coffee, but not caffeine, affects homocysteine metabolism within hours after intake, although the effect is still substantial after an overnight fast.

Costs of living for juvenile Chinook salmon (Oncorhynchus tshawytscha) in an increasingly warming and invaded world

USGS Publications Warehouse

Kuehne, Lauren M.; Olden, Julian D.; Duda, Jeffrey J.

2012-01-01

Rapid environmental change in freshwater ecosystems has created a need to understand the interactive effects of multiple stressors, with temperature and invasive predators identified as key threats to imperiled fish species. We tested the separate and interactive effects of water temperature and predation by non-native smallmouth bass (Micropterus dolomieu) on the lethal (mortality) and sublethal (behavior, physiology, and growth) effects for juvenile Chinook salmon (Oncorhynchus tshawytscha) in seminatural stream channel experiments. Over 48 h trials, there was no difference in direct predation with warmer temperatures, but significant interactive effects on sublethal responses of juvenile salmon. Warmer temperatures resulted in significantly stronger and more variable antipredator responses (surface shoaling and swimming activity), while physiological indicators (plasma glucose, plasma cortisol) suggested suppression of physiological mechanisms in response to the combined stressors. These patterns corresponded with additive negative growth in predation, temperature, and combined treatments. Our results suggest that chronic increases in temperature may not increase direct predation over short periods, but can result in significant sublethal costs with negative implications for long-term development, disease resistance, and subsequent size-selective mortality of Pacific salmon.

Mitigation of Alfvenic activity by 3D magnetic perturbations on NSTX

DOE PAGES

Kramer, G. J.; Bortolon, A.; Ferraro, N. M.; ...

2016-07-05

Observations on the National Spherical Torus eXperiment (NSTX) indicate that externally applied non-axisymmetric magnetic perturbations (MP) can reduce the amplitude of Toroidal Alfven Eigenmodes (TAE) and Global Alfven Eigenmodes (GAE) in response to pulsed n=3 non-resonant fields. From full-orbit following Monte Carlo simulations with the 1- and 2-fluid resistive MHD plasma response to the magnetic perturbation included, it was found that in response to MP pulses the fast-ion losses increased and the fast-ion drive for the GAEs was reduced. The MP did not affect the fast-ion drive for the TAEs significantly but the Alfven continuum at the plasma edge wasmore » found to be altered due to the toroidal symmetry breaking which leads to coupling of different toroidal harmonics. The TAE gap was reduced at the edge creating enhanced continuum damping of the global TAEs, which is consistent with the observations. Furthermore, the results suggest that optimized non-axisymmetric MP might be exploited to control and mitigate Alfven instabilities by tailoring the fast-ion distribution function and/or continuum structure.« less

Emergence of kinetic behavior in streaming ultracold neutral plasmas

DOE Office of Scientific and Technical Information (OSTI.GOV)

McQuillen, P.; Castro, J.; Bradshaw, S. J.

2015-04-15

We create streaming ultracold neutral plasmas by tailoring the photoionizing laser beam that creates the plasma. By varying the electron temperature, we control the relative velocity of the streaming populations, and, in conjunction with variation of the plasma density, this controls the ion collisionality of the colliding streams. Laser-induced fluorescence is used to map the spatially resolved density and velocity distribution function for the ions. We identify the lack of local thermal equilibrium and distinct populations of interpenetrating, counter-streaming ions as signatures of kinetic behavior. Experimental data are compared with results from a one-dimensional, two-fluid numerical simulation.

Molecularly imprinted polymer based electrochemical detection of L-cysteine at carbon paste electrode.

PubMed

Aswini, K K; Vinu Mohan, A M; Biju, V M

2014-04-01

A methacrylic acid (MAA) based molecularly imprinted polymer (MIP) modified carbon paste electrode (CPE) was developed for electrochemical detection of L-cysteine (Cys). Characterisation of MIP was done with FTIR and the modified electrode with cyclic voltammetry (CV) and differential pulse voltammetry (DPV). CV, DPV and impedance analysis demonstrated that the modified electrode is responsive towards the target molecule. The optimum percentage composition of MIP for MIP/CPE and the effect of pH towards the electrode response for Cys were studied. The detection of Cys in the range of 2×10(-8) to 18×10(-8)M at MIP/CPE was monitored by DPV with a limit of detection of 9.6nM and R(2) of 0.9974. Also, various physiological interferents such as ascorbic acid, L-tryptophan, D-glucose, D-cysteine and L-cysteine were found to have little effect on DPV response at MIP/CPE. The utility of the electrode was proved by the effective detection of Cys from tap water and human blood plasma samples with reproducible results. Copyright © 2014 Elsevier B.V. All rights reserved.

Does granulocyte colony-stimulating factor ameliorate the proinflammatory response in human meningococcal septic shock?

PubMed

Rojahn, Astrid; Brusletto, Berit; Øvstebø, Reidun; Haug, Kari B F; Kierulf, Peter; Brandtzaeg, Petter

2008-09-01

To test the hypothesis that granulocyte colony-stimulating factor acts cooperatively with interleukin-10 in down-regulating monocyte function in severe meningococcal septic shock. 1) We quantified the plasma levels of granulocyte colony-stimulating factor, interleukin-10, Neisseria meningitidis lipopolysaccharide and the number of N. meningitidis DNA copies in 28 patients with systemic meningococcal disease. 2) We studied the inhibitory effect of recombinant human granulocyte colony-stimulating factor on normal human monocytes stimulated with purified meningococcal lipopolysaccaride. 3) We monitored the inhibitory effects of endogenously produced granulocyte colony-stimulating factor and interleukin-10 in meningococcal shock plasmas on monocytes. Comparative, experimental study. University Hospital and laboratory. Twenty-eight patients with systemic meningococcal disease, 13 with persistent shock, 7 died, and 15 without shock. The median levels of granulocyte colony-stimulating factor in shock and nonshock patients were 1.7 x 10(6) and 8.1 x 10(2) pg/mL; interleukin-10, 2.1 x 10(4) and 4 x 10(1) pg/mL; number of N. meningitidis DNA copies, 2.9 x 10(7) and <10(3)/mL; and lipopolysaccharide, 105 and <0.04 endotoxin units/mL, respectively. The plasma levels of granulocyte colony-stimulating factor were reduced by 50% within 4 to 6 hrs after initiation of antibiotic treatment. In model experiments with lipopolysaccharide-stimulated human monocytes, recombinant human granulocyte colony-stimulating factor and interleukin-10 reduced the release of tumor necrosis factor-alpha by mean 30% and 92%, respectively. When plasmas from three shock patients were depleted of native granulocyte colony-stimulating factor or interleukin-10 by immunoprecipitation, no increase in tumor necrosis factor-alpha release occurred after removal of granulocyte colony-stimulating factor, whereas removal of interleukin-10 increased the tumor necrosis factor-alpha release eight-fold. Although granulocyte colony-stimulating factor in plasma increases by five orders of magnitude in patients with meningococcal shock, the anti-inflammatory effect on patients' monocytes is uncertain.

Raltegravir plasma concentrations in treatment-experienced patients receiving salvage regimens based on raltegravir with and without maraviroc coadministration.

PubMed

Baroncelli, Silvia; Villani, Paola; Weimer, Liliana E; Ladisa, Nicoletta; Francisci, Daniela; Tommasi, Chiara; Vullo, Vincenzo; Preziosi, Roberta; Cicalini, Stefania; Cusato, Maria; Galluzzo, Clementina; Floridia, Marco; Regazzi, Mario

2010-05-01

Raltegravir and maraviroc represent new, important resources for HIV-infected patients with intolerance or resistance to other antiretroviral agents. The safety and efficacy of both drugs have been investigated, but there is no information on possible pharmacokinetic interactions between these 2 drugs in clinical practice. To evaluate raltegravir plasma concentrations in heavily treatment-experienced patients receiving salvage regimens and explore, in a preliminary assessment, the potential influence of maraviroc coadministration and other cofactors on raltegravir trough concentrations (C(trough)). Fifty-four HIV-infected patients with triple class (nucleoside reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, protease inhibitor) treatment experience starting raltegravir 400 mg twice daily, with (n = 11) or without (n = 43) concomitant maraviroc 300 mg twice daily, were evaluated. All regimens included at least 3 drugs of at least 2 different classes. Raltegravir plasma Ctrough, after at least 1 month of treatment, were analyzed to compare groups of patients taking raltegravir only and raltegravir plus maraviroc. Immunovirological (CD4, HIV-RNA) and clinical data after 6 months of treatment were also collected and described. Raltegravir plasma Ctrough showed a large variability (range <0.020-2.47 microg/mL). Median levels were similar in the 2 groups (raltegravir + maraviroc 0.104 microg/mL, range 0.025-0.826; raltegravir 0.090 microg/mL, range <0.020-2.47, p = 0.400). Detectable (>0.02 microg/mL) raltegravir concentrations were observed in all patients receiving raltegravir + maraviroc and in 74% of patients receiving raltegravir alone (p = 0.060). After 6 months of treatment, the 2 groups had similar clinical, virologic, and immunologic conditions. Coadministration of maraviroc does not seem to have any relevant effects on raltegravir plasma Ctrough in heavily treatment-experienced patients receiving salvage regimens. Further studies should evaluate the potential additional benefits of maraviroc coadministration in terms of virologic and immunologic response.

Highly sensitive LC-MS/MS-ESI method for determination of phenelzine in human plasma and its application to a human pharmacokinetic study.

PubMed

Kallem, Raja Reddy; Jillela, Bhupathi; Ravula, Arun Reddy; Samala, Ramakrishna; Andy, Adinarayana; Ramesh, Mullangi; Rao, Jvln Seshagiri

2016-06-01

A selective, sensitive and rapid LC-MS/MS method has been developed and validated for quantification of the phenelzine (PZ) in 200μL of human plasma using hydroxyzine (HZ) as an internal standard (IS) as per regulatory guidelines. The sample preparation involved the derivatization of PZ using pentaflurobenzaldehyde followed by solid phase extraction process to extract PZ and HZ from human plasma. LC-MS/MS was operated under the multiple reaction-monitoring mode (MRM) using the electro spray ionization technique in positive ion mode and the transitions of m/z 305.1→105.1 and m/z 375.3→201.1 were used to measure the derivative of PZ and IS, respectively. The total run time was 3.5min and the elution of PZ and HZ occurred at 2.53, and 1.92min, respectively; this was achieved with a mobile phase consisting of 10mM ammonium acetate: acetonitrile (20:80, v/v) at a flow rate of 1.0mL/min on an Ace C18 column with a split ratio of 70:30. The developed method was validated in human plasma with a lower limit of quantitation 0.51ng/mL. A linear response function was established for the range of concentrations 0.51-25.2ng/mL (r>0.995) for PZ. The intra- and inter-day precision values met the acceptance criteria. PZ was stable in the battery of stability studies viz., stock solution, bench-top, auto-sampler, long-term and freeze/thaw cycles. The developed assay method was applied to an oral bioequivalence study in humans. Copyright © 2016 Elsevier B.V. All rights reserved.

A sensitive LC-MS/MS method for the quantification of febuxostat in human plasma and its pharmacokinetic application.

PubMed

Vaka, Venkata Rami Reddy; Inamadugu, Jaswanth Kumar; Pilli, Nageswara Rao; Ramesh, Mullangi; Katreddi, Hussain Reddy

2013-11-01

An improved, simple and highly sensitive LC-MS/MS method has been developed and validated for quantification of febuxostat with 100 μL human plasma using febuxostat-d7 as an internal standard (IS) according to regulatory guidelines. The analyte and IS were extracted from human plasma via liquid-liquid extraction using diethyl ether. The chromatographic separation was achieved on a Zorbax C18 column using a mixture of acetonitrile and 5 mm ammonium formate (60:40, v/v) as the mobile phase at a flow rate of 0.5 mL/min. The total run time was 5.0 min and the elution of febuxostat and IS occurred at 1.0 and 1.5 min, respectively. A linear response function was established for the range of concentrations 1-6000 ng/mL (r > 0.99). The precursor to product ion transitions monitored for febuxostat and IS were m/z 317.1 → 261.1 and 324.2 → 262.1, respectively. The intra- and inter-day precisions (%RSD) were within 1.29-9.19 and 2.85-7.69%, respectively. The proposed method was successfully applied to pharmacokinetic studies in humans. Copyright © 2013 John Wiley & Sons, Ltd.

Bioavailability of astaxanthin stereoisomers from wild (Oncorhynchus spp.) and aquacultured (Salmo salar) salmon in healthy men: a randomised, double-blind study.

PubMed

Rüfer, Corinna E; Moeseneder, Jutta; Briviba, Karlis; Rechkemmer, Gerhard; Bub, Achim

2008-05-01

The objective of the present study was to investigate the bioavailability and the configurational isomer distribution of the carotenoid astaxanthin (AST) in human plasma after ingestion of wild (Oncorhynchus spp.) and aquacultured (Salmo salar) salmon. In a randomised and double-blind trial, twenty-eight healthy men consumed 250 g wild or aquacultured salmon daily for 4 weeks which provided 5 mug AST/g salmon flesh. The plasma AST concentrations as well as the isomer distribution were measured by HPLC using a reversed and a chiral stationary phase. After 6 d of intervention with salmon, plasma AST concentrations reached a plateau of 39 nmol/l after consumption of wild salmon and of 52 nmol/l after administration of aquacultured salmon. At days 3, 6, 10 and 14 -- but not at day 28 -- the AST concentrations in human plasma were significantly greater after ingestion of aquacultured salmon. After administration of wild salmon, the (3S,3'S) isomer predominated in plasma (80 %), whereas after intake of aquacultured salmon the meso form (3R,3'S) prevailed (48 %). Therefore, the AST isomer pattern in human plasma resembles that of the ingested salmon. However, after consumption of both wild and aquacultured salmon for 28 d the relative proportion of the (3S,3'S) isomer was slightly higher and the (3R,3'R) form lower in human plasma compared with the isomer distribution in salmon flesh. A selective process of isomer absorption could be responsible for the observed differences in the relative proportions of the (3S,3'S) and (3R,3'R) isomers in human plasma compared with salmon flesh.

Effects of hyperthyroidism and hypothyroidism on rat growth hormone release induced by thyrotropin-releasing hormone.

PubMed

Chihara, K; Kato, Y; Ohgo, S; Iwasaki, Y; Maeda, K

1976-06-01

The effect of synthetic thyrotropin-releasing hormone (TRH) on the release of growth hormone (GH) and thyroid-stimulating hormone (TSH) was investigated in euthyroid, hypothyroid, and hyperthyroid rats under urethane anesthesia. In euthyroid control rats, intravenous injection of TRH (200 ng/100 g BW) resulted in a significant increase in both plasma GH and TSH. In rats made hypothyroid by treatment with propylthiouracil or by thyroidectomy, basal GH and TSH levels were significantly elevated with exaggerated responses to TRH. In contrast, plasma GH and TSH responses to TRH were both significantly inhibited in rats made hyperthyroid by L-thyroxine (T4) treatment. These results suggest that altered thyroid status influences GH release as well as TSH secretion induced by TRH in rats.

Cold Plasmas for Biofilm Control: Opportunities and Challenges.

PubMed

Gilmore, Brendan F; Flynn, Padrig B; O'Brien, Séamus; Hickok, Noreen; Freeman, Theresa; Bourke, Paula

2018-06-01

Bacterial biofilm infections account for a major proportion of chronic and medical device associated infections in humans, yet our ability to control them is compromised by their inherent tolerance to antimicrobial agents. Cold atmospheric plasma (CAP) represents a promising therapeutic option. CAP treatment of microbial biofilms represents the convergence of two complex phenomena: the production of a chemically diverse mixture of reactive species and intermediates, and their interaction with a heterogeneous 3D interface created by the biofilm extracellular polymeric matrix. Therefore, understanding these interactions and physiological responses to CAP exposure are central to effective management of infectious biofilms. We review the unique opportunities and challenges for translating CAP to the management of biofilms. Copyright © 2018. Published by Elsevier Ltd.

Can platelet-rich plasma enhance anterior cruciate ligament and meniscal repair?

PubMed

Hutchinson, Ian D; Rodeo, Scott A; Perrone, Gabriel S; Murray, Martha M

2015-02-01

The use of platelet-rich plasma (PRP) to improve clinical outcome following a soft tissue injury, regeneration, and repair has been the subject of intense investigation and discussion. This article endeavors to relate clinical and basic science strategies focused on biological augmentation of the healing response in anterior cruciate ligament (ACL) and meniscus repair and replacement using PRP. Therein, a translational feedback loop is created in the literature and targeted towards the entire multidisciplinary team. Ultimately, it is hoped that the theoretical benefits of PRP on soft-tissue interfacial healing will emerge clinically following a careful, focused characterization at the benchtop, and prospective randomized controlled clinical study. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Altering plasma sodium concentration rapidly changes blood pressure during haemodialysis.

PubMed

Suckling, Rebecca J; Swift, Pauline A; He, Feng J; Markandu, Nirmala D; MacGregor, Graham A

2013-08-01

Plasma sodium is increased following each meal containing salt. There is an increasing interest in the effects of plasma sodium concentration, and it has been suggested that it may have direct effects on blood pressure (BP) and possibly influences endothelial function. Experimental increases of plasma sodium concentration rapidly raise BP even when extracellular volume falls. Ten patients with end-stage renal failure established on haemodialysis were studied during the first 2 h of dialysis without fluid removal during this period. They were randomized to receive haemodialysis with (i) dialysate sodium concentration prescribed to 135 mmol/L and (ii) 145 mmol/L in random order in a prospective, single-blinded crossover study. BP measurements and blood samples were taken every 30 min. Pre-dialysis sitting BP was 137/76 ± 7/3 mmHg. Lower dialysate sodium concentration (135 mmol/L) reduced plasma sodium concentration [139.49 ± 0.67 to 135.94 ± 0.52 mmol/L (P < 0.001)], whereas plasma sodium concentration was not altered by higher dialysate sodium (145 mmol/L) (140.17 ± 0.66 mmol/L at baseline to 140.72 ± 0.43 mmol/L at 120 min). Systolic BP was lower with dialysate sodium concentration 135 mmol/L [area under the curve (AUC) 15823.50 ± 777.15 (mmHg)min] compared with 145 mmol/L [AUC 17018.20 ± 1102.17 (mmHg)min], mean difference 1194.70 ± 488.41 (mmHg)min, P < 0.05. There was a significant positive relationship between change in plasma sodium concentration and change in systolic BP. This direct relationship suggests that a fall of 1 mmol/L in plasma sodium concentration would be associated with a 1.7 mmHg reduction in systolic BP (P < 0.05). The potential mechanism for the increase in BP seen with salt intake may be through small but significant changes in plasma sodium concentration.

Influence of exercise on plasma ammonia and urea after ingestion beverages of carbohydrate electrolyte

NASA Astrophysics Data System (ADS)

Rusip, Gusbakti; Mukti Suhartini, Sri; Boon Suen, Ang

2018-03-01

Ingestion of beverages with carbohydrate electrolyte during exercise can delay fatigue. Fatigue caused by the decreasing of glycogen deposit source and indefensible reproduced ATP result in the improvement of IMP and ammonia during fatigue. The aim of this research was to observe the alteration of plasma ammonia and urea before, during and after exercise, after ingestion beverages of carbohydrate - electrolyte. Ten male subjects (age 18-30 years) were subjected to there cycle ergometer at 60% of VO2max with a pedal speed of 60 rpm until there is fatigued. The subject was given a drink of carbohydrate-electrolyte at a concentration of 6%, 12% and a flavored water placebo (P) to consume the volume of 3 ml/kg BW every 20 minutes. Blood samples were taken at rest and every 20 minutes until fatigue for analyzing plasma ammonia and urea. Mean exercise until fatigue show that no difference for three beverages. However, plasma ammonia and urea were significantly increase compared before and after exercise (p<0.001). Results of plasma ammonia before exercise for beverages CHO 12% (HC) (31.86±1.93μml/l vs 86.50±5.13μml/l), for CHO 6% (MC) (33.08±1.43μml/l vs 90.68±3.41μml/l), for no carbohydrate (P) (33.64±1.93μml/l vs 93.12 ± 2.91μml/l). Whereas plasma urea before exercise for beverages CHO 12% (4.75±0.12mmol/l vs 5.44±0.10mmol/l), for CHO 6% (4.88±0.20mmol/l vs 5.22± 0.10mmol/l), for Placebo (4.88±0.20mmol/l vs 5.54±0.24mmol/l). Conclusions that increase of plasma ammonia of during fatigue, can become the criteria for determining intensity exercise until fatigue results are better than plasma lactate.

The Effects of Acute Waterborne Exposure to Sublethal Concentrations of Molybdenum on the Stress Response in Rainbow Trout, Oncorhynchus mykiss

PubMed Central

Ricketts, Chelsea D.; Bates, William R.; Reid, Scott D.

2015-01-01

To determine if molybdenum (Mo) is a chemical stressor, fingerling and juvenile rainbow trout (Oncorhynchus mykiss) were exposed to waterborne sodium molybdate (0, 2, 20, or 1,000 mg l-1 of Mo) and components of the physiological (plasma cortisol, blood glucose, and hematocrit) and cellular (heat shock protein [hsp] 72, hsp73, and hsp90 in the liver, gills, heart, and erythrocytes and metallothionein [MT] in the liver and gills) stress responses were measured prior to initiation of exposure and at 8, 24, and 96 h. During the acute exposure, plasma cortisol, blood glucose, and hematocrit levels remained unchanged in all treatments. Heat shock protein 72 was not induced as a result of exposure and there were no detectable changes in total hsp70 (72 and 73), hsp90, and MT levels in any of the tissues relative to controls. Both fingerling and juvenile fish responded with similar lack of apparent sensitivity to Mo exposure. These experiments demonstrate that exposure to waterborne Mo of up to 1,000 mg l-1 did not activate a physiological or cellular stress response in fish. Information from this study suggests that Mo water quality guidelines for the protection of aquatic life are highly protective of freshwater fish, namely rainbow trout. PMID:25629693

Analytical and clinical performance of the Hologic Aptima HCV Quant Dx Assay for the quantification of HCV RNA in plasma samples.

PubMed

Schønning, Kristian; Pedersen, Martin Schou; Johansen, Kim; Landt, Bodil; Nielsen, Lone Gilmor; Weis, Nina; Westh, Henrik

2017-10-01

Chronic hepatitis C virus (HCV) infection can be effectively treated with directly acting antiviral (DAA) therapy. Measurement of HCV RNA is used to evaluate patient compliance and virological response during and after treatment. To compare the analytical performance of the Aptima HCV Quant Dx Assay (Aptima) and the COBAS Ampliprep/COBAS TaqMan HCV Test v2.0 (CAPCTMv2) for the quantification of HCV RNA in plasma samples, and compare the clinical utility of the two tests in patients undergoing treatment with DAA therapy. Analytical performance was evaluated on two sets of plasma samples: 125 genotyped samples and 172 samples referred for quantification of HCV RNA. Furthermore, performance was evaluated using dilutions series of four samples containing HCV genotype 1a, 2b, 3a, and 4a, respectively. Clinical utility was evaluated on 118 plasma samples obtained from 13 patients undergoing treatment with DAAs. Deming regression of results from 187 plasma samples with HCV RNA >2 Log IU/mL indicated that the Aptima assay quantified higher than the CAPCTMv2 test for HCV RNA >4.9 Log IU/mL. The linearity of the Aptima assay was excellent across dilution series of four HCV genotypes (slope of the regression line: 1.00-1.02). The Aptima assay detected significantly more replicates below targeted 2 Log IU/mL than the CAPCTMv2 test, and yielded clearly interpretable results when used to analyze samples from patients treated with DAAs. The analytical performance of the Aptima assay makes it well suited for monitoring patients with chronic HCV infection undergoing antiviral treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Critical evaluation of lowering the recommended dietary intake of folate.

PubMed

Obeid, Rima; Koletzko, Berthold; Pietrzik, Klaus

2014-04-01

We evaluated the recommendation of the Austrian, German, and Swiss Societies for Nutrition of lowering dietary folate intake from 400 to 300 μg dietary folate equivalents/d. A dose-response relation exists between folate intake or plasma level and disease risk within the normal range. Improving folate status can prevent between 30% and 75% of neural tube defects. A prepregnancy plasma folate of >18.0 nmol/L (mean 26.1 nmol/L) is associated with low total homocysteine (tHcy) (<10.0 μmol/L) and optimal prevention of birth defects. Because the closure of the neural tube occurs in the first 8 weeks after conception, women with low prepregnancy folate intake cannot achieve maximal risk reduction. The Austrian, German, and Swiss Societies for Nutrition recommend that young women should additionally supplement with 400 μg folic acid at least 4 weeks before conception. This short time window is not sufficient to achieve optimal plasma folate and tHcy levels in the majority of women. Factors affecting the relation between folate intake and blood biomarkers are total folate intake, baseline plasma folate, time available for supplement use, dose and form (folic acid or methyl folate), genetic polymorphisms, physiological and lifestyle factors. Lowering the recommended dietary folate intake may have important public health consequences. Elderly people and young women are at risk for diseases related to folate shortage. Reducing birth defects through supplementation of folic acid remains a poor option, as <20% of young women (i.e., in Germany) supplement with the vitamin. Recommending adequate food folate intake is crucial for reaching the target protective plasma folate levels in the population. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Development and full validation of an UPLC-MS/MS method for the determination of an anti-allergic indolinone derivative in rat plasma, and application to a preliminary pharmacokinetic study.

PubMed

Oufir, Mouhssin; Sampath, Chethan; Butterweck, Veronika; Hamburger, Matthias

2012-08-01

The natural product (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolin-2-one (indolinone) was identified some years ago as a nanomolar inhibitor of FcɛRI-receptor dependent mast cell degranulation. To further explore the potential of the compound, we established an UPLC-MS/MS assay for dosage in rat plasma. The method was fully validated according to FDA Guidance for industry. Results of this validation and long term stability study demonstrate that the method in lithium heparinized rat plasma is specific, accurate, precise and capable of producing reliable results according to recommendations of international guidelines. The method was validated with a LLOQ of 30.0 ng/mL and an ULOQ of 3000 ng/mL. The response versus concentration data were fitted with a first order polynomial with 1/X(2) weighting. No matrix effect was observed when using three independent sources of rat plasma. The average extraction recovery was consistent over the investigated range. This validation in rat plasma demonstrated that indolinone was stable for 190 days when stored below -65 °C; for 4 days at 10 °C in the autosampler; for 4h at RT, and during three successive freeze/thaw cycles at -65 °C. Preliminary pharmacokinetic data were obtained in male Sprague-Dawley rats (2 mg/kg BW i.v.). Blood samples taken from 0 to 12 h after injection were collected, and data analyzed with WinNonlin. A short half-life (4.30±0.14 min) and a relatively high clearance (3.83±1.46 L/h/kg) were found. Copyright © 2012 Elsevier B.V. All rights reserved.

Decomposition of L-valine under nonthermal dielectric barrier discharge plasma.

PubMed

Li, Yingying; Kojtari, Arben; Friedman, Gary; Brooks, Ari D; Fridman, Alex; Ji, Hai-Feng

2014-02-13

L-Valine solutions in water and phosphate buffer were treated with nonthermal plasma generated by using a dielectric barrier discharge (DBD) device and the products generated after plasma treatments were characterized by (1)H NMR and GC-MS. Our results demonstrate that L-valine is decomposed to acetone, formic acid, acetic acid, threo-methylaspartic acid, erythro-methlyaspartic acid, and pyruvic acid after direct exposure to DBD plasma. The concentrations of these compounds are time-dependent with plasma treatment. The mechanisms of L-valine under the DBD plasma are also proposed in this study. Acetone, pyruvic acid, and organic radicals (•)CHO, CH3COCH2OO(•) (acetonylperoxy), and CH3COC(OH)2OO(•) (1,1-dihydroxypropan-2-one peroxy) may be the determining chemicals in DNA damage.

Exploration of the immunoreactivity of the Traditional Chinese medicine Shenrouyangzhentang to vasoactive intestinal polypeptide

PubMed Central

Gu, Yu-Chun; Chen, De-Zhen

1997-01-01

AIM: To study the immunoreactivity of the Chinese medicine Shenrouyangzhentang to vasoactive intestinal polypeptide (VIP) and its therapeutic mechanism. METHODS: The immunoreactivity of the Chinese medicine Shenrouyangzhentang to VIP was detected in the plasma of 20 normal people and 20 patients with Piyinxu (Spleen Yin deficiency) using the radioimmunoassay (RIA) method. RESULTS: The maximum binding rate B0/T was 53.29%, the non-specific binding rate N0/T was 1.170%, and the VIP standard curve was Y = 0.81983 + 0.44319X - 0.28927X2, R2 = 0.990. The VIP content in Shenrouyangzhentang was 106.6 ng/L ± 20 ng/L), while it was 90.16 ng/L ± 15 ng/L in normal human plasma and 63.25 ng/L ± 11 ng/L in the plasma of Pixinxu patients. The difference between normal plasma and Pixinxu patient plasma was statistically significant (P < 0.05). CONCLUSION: The Chinese medicine Shenrouyangzhentang demonstrated VIP immunoreactivity similar to that of normal plasma. The (vasoactive intestinal polypeptide) VIP content in Pixinxu patient plasma was lower than that in healthy subjects (P < 0.05). PMID:27041949

Evaluation of a tunable bandpass reaction cell for an inductively coupled plasma mass spectrometer for the determination of chromium and vanadium in serum and urine

NASA Astrophysics Data System (ADS)

Nixon, David E.; Neubauer, Kenneth R.; Eckdahl, Steven J.; Butz, John A.; Burritt, Mary F.

2002-05-01

A Dynamic Reaction Cell™ inductively coupled argon plasma mass spectrometer (DRC-ICP-MS) was evaluated for the determination of chromium and vanadium in serum and urine. Reaction cell conditions were evaluated for the elimination of ArC + and ClOH + interferences on chromium at mass 52 and OCl + on vanadium at mass 51. A diluent containing only 1% nitric acid and internal standards (Y and Ga) was used to prepare serum and urine for analysis. Instrument response calibration was achieved by using aqueous acidic standards spiked into pooled sera or urine matrices. The slopes of the calibration curves prepared in urine and serum matrices were nearly identical. On average, chromium detection limits are 2.5 times lower using the DRC than Zeeman graphite furnace atomic absorption spectrometry (ZGFAAS). Vanadium detection limits are approximately 50 times lower. Average detection limits achieved with DRC-ICP-MS are 0.075 μg Cr/l and 0.028 μg V/l. Average results for the analysis of National Institute of Standards and Technology Standard Reference Material (NIST SRM) 1598 Bovine Serum (attained over 22 days) are: 0.14 μg Cr/l and 0.068 μg V/l. The reference concentrations for vanadium and chromium in NIST SRM 1598 are (0.06) μg V/l and 0.14±0.08 μg Cr/l, respectively. Results for chromium and vanadium determinations on ICP-MS survey samples from the Toxocologie du Quebec are equivalent to those reported by high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS) for the same survey samples.

Predictions of the near edge transport shortfall in DIII-D L-mode plasmas using the trapped gyro-Landau-fluid model [Predictions of the near edge transport shortfall in DIII-D L-mode plasmas using the TGLF model

DOE PAGES

Kinsey, Jon E.; Staebler, Gary M.; Candy, Jefferey M.; ...

2015-01-14

Previous studies of DIII-D L-mode plasmas have shown that a transport shortfall exists in that our current models of turbulent transport can significantly underestimate the energy transport in the near edge region. In this paper, the Trapped Gyro-Landau-Fluid (TGLF) drift wave transport model is used to simulate the near edge transport in a DIII-D L-mode experiment designed to explore the impact of varying the safety factor on the shortfall. We find that the shortfall systematically increases with increasing safety factor and is more pronounced for the electrons than for the ions. Within the shortfall dataset, a single high current casemore » has been found where no transport shortfall is predicted. Reduced neutral beam injection power has been identified as the key parameter separating this discharge from other discharges exhibiting a shortfall. Further analysis shows that the energy transport in the L-mode near edge region is not stiff according to TGLF. Unlike the H-mode core region, the predicted temperature profiles are relatively more responsive to changes in auxiliary heating power. In testing the fidelity of TGLF for the near edge region, we find that a recalibration of the collision model is warranted. A recalibration improves agreement between TGLF and nonlinear gyrokinetic simulations performed using the GYRO code with electron-ion collisions. As a result, the recalibration only slightly impacts the predicted shortfall.« less

Circulating programmed death ligand-1 (cPD-L1) in non-small-cell lung cancer (NSCLC)

PubMed Central

Vecchiarelli, Silvia; Passiglia, Francesco; D’Incecco, Armida; Gallo, Marianna; De Luca, Antonella; Rossi, Elisa; D’Incà, Federica; Minuti, Gabriele; Landi, Lorenza; Bennati, Chiara; Spreafico, Michela; D’Arcangelo, Manolo; Mazza, Valentina; Normanno, Nicola; Cappuzzo, Federico

2018-01-01

Background This study aimed at investigating feasibility of programmed death ligand-1 (PD-L1) testing in plasma samples of advanced NSCLC patients receiving first-line treatment, assessing whether circulating (c)PD-L1 levels were modified by the therapy and whether baseline cPD-L1 levels were associated with patients’ clinical responses and survival outcome. Methods Peripheral blood samples were collected from 16 healthy volunteers and 56 newly diagnosed NSCLC patients before and at 12th week during the course of first-line therapy. The level of PD-L1 was measured in plasma samples using the human (PD-L1/CD274) ELISA kit (CUSABIO, MD, USA). The Mann Whitney test or Fisher’s test were used for comparisons. Survival analysis was performed using Kaplan Meyer method, providing median and p-value. Results Baseline median cPD-L1 was 42.21 pg/ml (range 12.00-143.49) in NSCLC patients and 37.81 pg/ml (range 9.73-90.21) in healthy control cohort (p = 0.78). Median cPD-L1 increased in patients treated with first-line chemotherapy (63.20 pg/ml vs 39.34 pg/ml; p = 0.002), with no changes in patients exposed to non-chemotherapy drugs (42.39 pg/ml vs 50.67 pg/ml; p = 0.398). Time to progression and overall survival were 4.4 vs 6.9 months (p = 0.062) and 8.8 vs 9.3 months (p = 0.216) in cPD-L1 positive vs cPD-L1 negative patients. Baseline cPD-L1 levels increased with the ascending number of metastatic sites, even if the association was not statistically significant (p = 0.063). Conclusions This study showed that cPD-L1 testing is feasible, with chemotherapy influencing PD-L1 plasma levels. The possibility of using such test for predicting or monitoring the effect of immunotherapy or combination of chemotherapy and immunotherapy warrant further investigations. PMID:29707129

Vascular smooth muscle cell polyploidy and cardiomyocyte hypertrophy due to chronic NOS inhibition in vivo.

PubMed

Devlin, A M; Brosnan, M J; Graham, D; Morton, J J; McPhaden, A R; McIntyre, M; Hamilton, C A; Reid, J L; Dominiczak, A F

1998-01-01

To assess the vascular and cardiac response to NO (nitric oxide) synthase (NOS) blockade in vivo, Wistar-Kyoto rats (WKY) were treated for 3 wk with NG-nitro-L-arginine methyl ester (L-NAME; 10 mg.kg-1.day-1). L-NAME treatment induced hypertension that was associated with increased plasma renin activity. Flow cytometry cell cycle DNA analysis showed that aortic vascular smooth muscle cells (VSMC) from L-NAME-treated WKY had a significantly higher polyploid population compared with WKY controls. Using organ bath experiments, we have shown that aortic rings from L-NAME-treated WKY have an increased contractile response to phenylephrine and impaired relaxation to carbachol compared with control rings. NOS blockade in vivo caused a significant increase in cardiac and left ventricular hypertrophy. Northern mRNA analysis of the myocardium showed that L-NAME treatment caused reexpression of the fetal skeletal alpha-actin isoform without alterations in collagen type I expression, a pattern indicating true hypertrophy of the cardiomyocytes. These studies provide further insight to confirm that NO deficiency in vivo results in the development of vascular and cardiac hypertrophy.

‘Nodophagy’

PubMed Central

Travassos, Leonardo H

2010-01-01

Autophagy is a homeostatic pathway that processes and recycles damaged organelles and other cytoplasmic contents. While studies have implicated autophagy in the immune response to infection, the understanding of how the autophagic machinery specifically targets intracellular pathogens has remained elusive. Two recent studies have uncovered an autophagy-mediated immune response to bacteria through their detection by Nod receptors. In particular, Nod1 and Nod2 recruit the autophagic protein ATG16L1 to the plasma membrane at the bacterial entry site to promote an autophagy-dependent elimination of bacteria. In addition, Nod2 and ATG16L1 synergize to initiate an adaptive immune response to bacterial invasion by enhancing major histocompatibility complex (MHC) class II antigen presentation. These findings link two Crohn disease-associated susceptibility genes and reveal that cells expressing the risk-associated variants of ATG16L1 are defective in autophagy-mediated bacterial handling and antigen presentation. This could lead to bacterial persistence and contribute to the pathogenesis of the disease. PMID:21327039

Cardiovascular effects of torcetrapib in conscious and pentobarbital-anesthetized dogs.

PubMed

Polakowski, James S; King, Andrew J; Campbell, Thomas J; Nelson, Richard A; Preusser, Lee C; Kempf-Grote, Anita J; Marsh, Kennan C; Gintant, Gary A; Cox, Bryan F; Mittelstadt, Scott W

2009-12-01

Torcetrapib is a cholesteryl ester transfer protein inhibitor with an undesired response of increasing arterial pressure in humans. Pressor responses to torcetrapib have been demonstrated in multiple preclinical species. However, these studies have not related plasma concentrations to observed effects. Our purpose was to 1) characterize the cardiovascular responses of torcetrapib in conscious and anesthetized dogs with measured plasma concentrations; and 2) characterize the hemodynamic effects contributing to hypertension using comprehensively instrumented anesthetized dogs. Torcetrapib was dosed orally (3, 30 mg/kg) and intravenously (0.01, 0.33, 0.1 mg/kg) in conscious and anesthetized dogs, respectively. Mean arterial pressure and heart rate were monitored in both models; additional parameters were measured in anesthetized dogs. Plasma drug concentrations were assessed in both models. In conscious and anesthetized dogs, torcetrapib increased mean arterial pressure 25 and 18 mm Hg and heart rate 35 and 21 beats/min, at 2.94 and 3.99 microg/mL, respectively. In anesthetized dogs, torcetrapib increased pulmonary arterial pressure, both systemic and pulmonary hypertension driven by increases in vascular resistance. The compound increased rate pressure product and myocardial contractility while decreasing time to systolic pressure recovery and ejection time. Thus, torcetrapib-induced pressor responses are mediated by systemic and pulmonary vasoconstriction and are associated with increased myocardial oxygen consumption and positive inotropy.

Mechanical and chemical characteristics of an autologous glue.

PubMed

De Somer, Filip; Delanghe, Joris; Somers, Pamela; Debrouwere, Maarten; Van Nooten, Guido

2008-09-15

The study evaluates the mechanical and chemical characteristics of autologous surgical glue made by mixing ultrafiltered plasma with glutaraldehyde (GTA). Human albumin 200 g/L mixed with different concentrations of GTA (25, 50, 75, or 100 g/L) was used as a single protein set-up for testing tensile strength, elasticity, and rate of crosslinking. Subsequently, ultrafiltered canine or human plasma to obtain autologous glue replaced human albumin. BioGlue, a surgical glue, and Tissucol Duo, a fibrin sealant, were used as controls. Tensile strength of human albumin 200 g/L mixed with 75 g/L GTA is 825 +/- 109 N versus 672 +/- 167 N for BioGlue. Ultrafiltered canine plasma showed a maximum tensile strength of 634 +/- 137 N when mixed with GTA 75 g/L. For human plasma, the maximum tensile strength of 436 +/- 69 N was reached after mixing with GTA 25 g/L. Autologous glue had a higher elasticity of 144 +/- 66 N versus 322 +/- 104 N for BioGlue at maximum load. Autologous glues for vascular repair can be easily prepared out of the patient's plasma. The optimal characteristics, compared to BioGlue, are obtained for ultrafiltered canine and human plasma by mixing with a GTA concentration of 50-75 g/L and 25-50 g/L, respectively. The autologous glue will exert less tensile strength than BioGlue but has a better compliance. In case where no plasma can obtained from the patient, mixing human albumin 200 g/L with GTA 75 g/L can be an alternative to BioGlue.

Assessment of a bedside test for N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac causes of pleural effusion in cats.

PubMed

Wurtinger, Gabriel; Henrich, Estelle; Hildebrandt, Nicolai; Wiedemann, Nicola; Schneider, Matthias; Hassdenteufel, Esther

2017-12-20

Cats with pleural effusion represent common emergencies in small animal practice. The aim of this prospective study was to investigate the diagnostic ability of a point-of-care ELISA (POC-ELISA) for the measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) to differentiate cardiac from non-cardiac disease in cats with pleural effusion. The sample material for use of this rapid test was either plasma or diluted pleural effusion. Twenty cats with moderate to severe pleural effusion were prospectively recruited. The cats were grouped into two groups, with or without congestive heart failure (CHF; N-CHF), after complete work-up. Blood and effusion were collected in EDTA tubes. Plasma and pleural effusion supernatants were transferred into stabilizer tubes and frozen. POC-ELISA for NT-proBNP was performed with plasma and diluted effusion (1:1). Quantitative NT-proBNP measurement was performed in plasma and diluted and undiluted effusions. Six cats were assigned to the CHF group. Of the 14 cats in the N-CHF group, 6 had concurrent cardiac abnormalities that were not responsible for the effusion. For the detection of CHF, the test displayed respective sensitivities and specificities of 100% and 79% in plasma and 100% and 86% in diluted pleural fluid. Receiver operating characteristic (ROC) analysis for quantitative NT-proBNP measurement of plasma and diluted and undiluted pleural effusions displayed areas under the curve of 0.98, sensitivities of 100% and specificities of 86%. The optimum cut-off was calculated at 399 pmol/l in plasma and 229 pmol/l in the diluted effusion and 467 pmol/l in the undiluted effusion. POC-ELISA for NT-proBNP in both plasma and diluted pleural effusion was suitable to differentiate cardiac from non-cardiac causes of feline pleural effusion. According to our results, use of pleural effusion is feasible, but dilution of the effusion before measurement seems to improve specificity.

Hardness does not affect the physiological responses of wild and domestic strains of diploid and triploid rainbow trout Oncorhynchus mykiss to short-term exposure to pH 9.5.

PubMed

Thompson, W A; Rodela, T M; Richards, J G

2016-08-01

This study examined the effects of water hardness on the physiological responses associated with high pH exposure in multiple strains of diploid and triploid rainbow trout Oncorhynchus mykiss. To accomplish this, three wild strains and one domesticated strain of diploid and triploid O. mykiss were abruptly transferred from control soft water (City of Vancouver dechlorinated tap water; pH 6·7; [CaCO3 ] < 17·9 mg l(-1) ) to control soft water (handling control), high pH soft water (pH 9·5; [CaCO3 ] < 17·9 mg l(-1) ), or high pH hard water (pH 9·5; [CaCO3 ] = 320 mg l(-1) ) followed by sampling at 24 h for physiological measurements. There was a significant effect of ploidy on loss of equilibrium (LOE) over the 24 h exposure, with only triploid O. mykiss losing equilibrium at high pH in both soft and hard water. Furthermore, exposure to pH 9·5 resulted in significant decreases in plasma sodium and chloride, and increases in plasma and brain ammonia with no differences between soft and hard water. There was no significant effect of strain on LOE, but there were significant differences between strains in brain ammonia and plasma cortisol. Overall, there were no clear protective effects of hardness on high pH exposure in these strains of O. mykiss. © 2016 The Fisheries Society of the British Isles.

Homocysteine impaired endothelial function through compromised vascular endothelial growth factor/Akt/endothelial nitric oxide synthase signalling.

PubMed

Yan, Ting-Ting; Li, Qian; Zhang, Xuan-Hong; Wu, Wei-Kang; Sun, Juan; Li, Lin; Zhang, Quan; Tan, Hong-Mei

2010-11-01

1. Hyperhomocysteinaemia (HHcy) is associated with endothelial dysfunction and has been recognized as a risk factor of cardiovascular disease. The present study aimed to investigate the effect of homocysteine (Hcy) on endothelial function in vivo and in vitro, and the underlying signalling pathways. 2. The HHcy animal model was established by intragastric administration with l-methionine in rats. Plasma Hcy and nitric oxide (NO) concentration were measured by fluorescence immunoassay or nitrate reductase method, respectively. Vasorelaxation in response to acetylcholine and sodium nitroprusside were carried out on aortic rings. Human umbilical vein endothelial cells (HUVEC) were treated with indicated concentrations of Hcy in the in vitro experiments. Intracellular NO level and NO concentration in culture medium were assayed. The alterations of possible signalling proteins were detected by western blot analysis. 3. l-methionine administration induced a significant increase in plasma Hcy and decrease in plasma NO. Endothelium-dependent relaxation of aortic rings in response to acetylcholine was impaired in l-methionine-administrated rats. The in vitro study showed that Hcy reduced both intracellular and culture medium NO levels. Furthermore, Hcy decreased phosphorylation of endothelial nitric oxide synthase (eNOS) at serine-1177 and phosphorylation of Akt at serine-473. Hcy-induced dephosphorylation of eNOS at Ser-1177 was partially reversed by insulin (Akt activator) and GF109203X (PKC inhibitor). Furthermore, Hcy reduced vascular endothelial growth factor (VEGF) expression in a dose-dependent manner. 4. In conclusion, Hcy impaired endothelial function through compromised VEGF/Akt/endothelial nitric oxide synthase signalling. These findings will be beneficial for further understanding the role of Hcy in cardiovascular disease. © 2010 Blackwell Publishing Asia Pty Ltd.

Mucuna pruriens in Parkinson Disease: A Kinetic-Dynamic Comparison With Levodopa Standard Formulations.

PubMed

Contin, Manuela; Lopane, Giovanna; Passini, Andrea; Poli, Ferruccio; Iannello, Carmelina; Guarino, Maria

2015-01-01

We compared levodopa (LD) kinetic-dynamic profile of a dose of LD/aromatic amino acid decarboxylase peripheral inhibitors versus a nominally equivalent dose of a commercial Mucuna pruriens (Mucuna) seeds extract in 2 patients with Parkinson disease chronically taking LD standard combined with self-prescribed Mucuna. Patients were challenged with a fasting morning dose of 100 mg LD/25 mg carbidopa (patient 1) or benserazide (patient 2) versus 100 mg LD from Mucuna capsules in 2 different sessions, after a 12-hour standard LD formulations' washout. They underwent kinetic-dynamic LD monitoring based on LD dose intake and simultaneous serial assessments of plasma drug concentrations and motor test performances. Quantitative analysis of LD in Mucuna capsules was also performed. Levodopa bioavailability was markedly lower after Mucuna administration compared with LD standard formulations: in patient 1, peak plasma LD concentration (Cmax) decreased from 2.0 to 1.0 mg/L and the area under the plasma concentration time curve from 137 to 33.6 mg/L per minute; in patient 2, Cmax was 0.7 mg/L after LD/benserazide and nearly undetectable after Mucuna. In patient 1, impaired LD bioavailability from Mucuna resulted in reduced duration and overall extent of drug response compared with LD/carbidopa. In patient 2, no significant subacute LD motor response was observed in either condition. Quantitative analysis of Mucuna formulation confirmed the 100 mg LD content for the utilized capsules. Our results show an impaired LD bioavailability from Mucuna preparation, as expected by the lacking aromatic amino acid decarboxylase inhibitors coadministration, which might explain the suggested lower dyskinetic potential of Mucuna compared with standard LD formulations.

B-Type Natriuretic Peptide Assay for the Diagnosis and Prognosis of Patent Ductus Arteriosus in Preterm Infants

PubMed Central

Kim, Joon Sik

2012-01-01

Background and Objectives Patent ductus arteriosus (PDA) is a significant cause of morbidity and mortality in preterm infants. Measurement of plasma B-type natriuretic peptide (BNP) has been reported to be a useful bedside screening tool for the presence of hemodynamically significant PDA (hsPDA) in neonates. This study was conducted to investigate the usefulness of a BNP assay as a biochemical marker for the diagnosis of hsPDA and predictive biomarker of the response to indomethacin in preterm infants. Subjects and Methods Preterm infants born at <37 weeks' gestational age were prospectively enrolled within 24 hours of birth. Plasma BNP levels were measured on days 1, 4, and 7. Significant PDA was diagnosed by large ductal flow with left to right shunt on color Doppler echocardiography, along with clinical features of PDA. Following that, hsPDA was treated with indomethacin. Results A total of 28 preterm infants were prospectively enrolled in this study. Seven infants with PDA had higher on day 4 plasma BNP values (median 654.68 pg/mL; range 428.29-1280.00) compared to the control group (median 124.52 pg/mL; range 37.21-290.49). The area under the receiver operator characteristic curve for the detection of hsPDA was high: 0.998 (95% confidence interval: 0.995-1.002). The cutoff of BNP concentration for the diagnosis of hsPDA was determined to be 412 pg/mL (sensitivity: 100%; specificity: 95%). Conclusion B-type natriuretic peptide can be a useful biomarker for the screening and diagnosis of PDA in preterm infants. Serial BNP measurements are valuable for assessing the clinical course and indomethacin responsiveness of PDA. PMID:22493614

Responses of catecholestrogen metabolism to acute graded exercise in normal menstruating women before and after training.

PubMed

De Crée, C; Ball, P; Seidlitz, B; Van Kranenburg, G; Geurten, P; Keizer, H A

1997-10-01

It has been hypothesized that exercise-related hypo-estrogenemia occurs as a consequence of increased competition of catecholestrogens (CE) for catechol-O-methyltransferase (COMT). This may result in higher norepinephrine (NE) concentrations, which could interfere with normal gonadotropin pulsatility. The present study investigates the effects of training on CE responses to acute exercise stress. Nine untrained eumenorrheic women (mean percentage of body fat +/-SD: 24.8 +/- 3.1%) volunteered for an intensive 5-day training program. Resting, submaximal, and maximal (tmax) exercise plasma CE, estrogen, and catecholamine responses were determined pre- and post training in both the follicular (FPh) and luteal phase (LPh). Acute exercise stress increased total primary estrogens (E) but had little effect on total 2-hydroxyestrogens (2-OHE) and 2-hydroxyestrogen-monomethylethers (2-MeOE) (= O-methylated CE after competition for catechol-O-methyltransferase). This pattern was not significantly changed by training. However, posttraining LPh mean (+/-SE) plasma E, 2-OHE, and 2-MeOE concentrations were significantly lower (P < 0.05) at each exercise intensity (for 2-OHE: 332 +/- 47 vs. 422 +/- 57 pg/mL at tmax; for 2-MeOE: 317 +/- 26 vs. 354 +/- 34 pg/mL at tmax). Training produced opposite effects on 2-OHE:E ratios (an estimation of CE formation) during acute exercise in the FPh (reduction) and LPh (increase). The 2-MeOE:2-OHE ratio (an estimation of CE activity) showed significantly higher values at tmax in both menstrual phases after training (FPh: +11%; LPh: +23%; P < 0.05). After training, NE values were significantly higher (P < 0.05). The major findings of this study were that: training lowers absolute concentrations of plasma estrogens and CE; the acute exercise challenge altered plasma estrogens but had little effect on CE; estimation of the formation and activity of CE suggests that formation and O-methylation of CE proportionately increases. These findings may be of importance for NE-mediated effects on gonadotropin release.

Ultrafine particles and platelet activation in patients with coronary heart disease – results from a prospective panel study

PubMed Central

Rückerl, Regina; Phipps, Richard P; Schneider, Alexandra; Frampton, Mark; Cyrys, Josef; Oberdörster, Günther; Wichmann, H Erich; Peters, Annette

2007-01-01

Background Epidemiological studies on health effects of air pollution have consistently shown adverse cardiovascular effects. Toxicological studies have provided evidence for thrombogenic effects of particles. A prospective panel study in a susceptible population was conducted in Erfurt, Germany, to study the effects of daily changes in ambient particles on various blood cells and soluble CD40ligand (sCD40L, also known as CD154), a marker for platelet activation that can cause increased coagulation and inflammation. Blood cells and plasma sCD40L levels were repeatedly measured in 57 male patients with coronary heart disease (CHD) during winter 2000/2001. Fixed effects linear regression models were applied, adjusting for trend, weekday and meteorological parameters. Hourly data on ultrafine particles (UFP, number concentration of particles from 0.01 to 0.1 μm), mass concentration of particles less than 10 and 2.5 μm in diameter (PM10, PM2.5), accumulation mode particle counts (AP, 0.1–1.0 μm), elemental and organic carbon, gaseous pollutants and meteorological data were collected at central monitoring sites. Results An immediate increase in plasma sCD40L was found in association with UFP and AP (% change from geometric mean: 7.1; CI: [0.1, 14.5] and 6.9; CI: [0.5, 13.8], respectively). Platelet counts decreased in association with UFP showing an immediate, a three days delayed (lag 3) and a 5-day average response (% change from the mean: -1.8; CI: [-3.4,-0.2]; -2.4; CI: [-4.5,-0.3] and -2.2; CI: [-4.0,-0.3] respectively). Conclusion The increased plasma sCD40L levels support the hypothesis that higher levels of ambient air pollution lead to an inflammatory response in patients with CHD thus providing a possible explanation for the observed association between air pollution and cardiovascular morbidity and mortality in susceptible parts of the population. PMID:17241467

Cord blood neutrophils display a galectin-3 responsive phenotype accentuated by vaginal delivery

PubMed Central

2013-01-01

Background Term neonates are at increased risk of infections due to undeveloped immune mechanisms, and proper neutrophil function is important for perinatal immune defence. Galectin-3, an endogenous β-galactoside-binding lectin, is emerging as an inflammatory mediator and we have previously shown that primed/activated, but not resting, adult neutrophils respond to this lectin by production of reactive oxygen species (ROS). We investigated if galectin-3 is of importance in perinatal immune defence, focusing on plasma levels and neutrophil responsiveness. Methods Neutrophils were isolated from peripheral blood of healthy adults and cord blood (CB) after elective Caesarean section (CSCB) and vaginal delivery (VDCB). ROS production was measured by chemiluminescence, L-selectin expression by flow cytometry, and interleukin-8 (IL-8) and galectin-3 concentrations by ELISA. Statistical evaluations were performed using the Mann–Whitney test. Results In response to galectin-3, CSCB neutrophils showed a small but clear ROS production not evident in adult cells, signifying that neonatal neutrophils exist in a primed state. IL-8 production was elevated in CSCB cells while L-selectin exposure was equal to adult cells. Comparing CSCB to VDCB neutrophils, the latter showed an extensive galectin-3 responsiveness, indicating that the degree of priming is dependent on mode of delivery. VDCB neutrophils were increasingly prone to shed L-selectin, while the amount of IL-8 was similar to CSCB cells. The endogenous galectin-3 levels were higher in neonatal as compared to adult plasma, unaffected by mode of delivery. Conclusions Neutrophils enter a pre-primed state already in the fetus. Upon exposure to the inflammatory stimuli that are associated with labor, the neutrophils develop a reactive phenotype with extensive priming features. PMID:23964611

Evaluation of the methoxytriazine herbicide prometon using a short-term fathead minnow reproduction test and a suite of in vitro bioassays.

PubMed

Villeneuve, Daniel L; Murphy, Margaret B; Kahl, Michael D; Jensen, Kathleen M; Butterworth, Brian C; Makynen, Elizabeth A; Durhan, Elizabeth J; Linnum, Ann; Leino, Richard L; Curtis, Lawrence R; Giesy, John P; Ankley, Gerald T

2006-08-01

Prometon is one of the most consistently detected herbicides in the U.S. environment. However, no previous assessment of the potential for prometon or related methoxytriazine herbicides to act as endocrine-disrupting chemicals has been conducted. This study used an array of in vitro bioassays to assess whether prometon, atraton, terbumeton, or secbumeton might act as potent (ant)agonists of the aryl hydrocarbon, estrogen, androgen, or glucocorticoid receptors or as aromatase inhibitors or inducers in vitro. Potential effects of prometon were also evaluated using a 21-d fathead minnow reproduction assay. Concentrations of methoxytriazines, as great as 1 mg/L (4.4 microM), did not induce significant dioxin-like responses in H4IIE-luc cells, estrogenic responses in MVLN cells, or androgen or glucocorticoid receptor-mediated responses in MDA-kb2 cells, nor did the methoxytriazines significantly affect aromatase activity in vitro. In the fathead minnow assay, exposure to 20, 200, or 1,000 microg prometon/L significantly reduced the weight of the male fat pad (an androgen-responsive tissue) relative to body weight. Exposure to 20 microg prometon/L significantly increased female plasma testosterone concentrations, but the effect was not observed at greater concentrations. Overall, prometon did not significantly reduce fecundity over the 21-d exposure, nor were other endpoints, including plasma vitellogenin and estradiol concentrations, brain and ovary aromatase activity, and male tubercle index, significantly affected. Evidence from our work suggests that prometon may cause subtle endocrine and/or reproductive effects in fathead minnows, but no clear mechanism of action was observed. The relevance of these effects to hazard assessment for the pesticide is uncertain.

Plasma Deactivation of Oral Bacteria Seeded on Hydroxyapatite Disks as Tooth Enamel Analogue

PubMed Central

Blumhagen, Adam; Singh, Prashant; Mustapha, Azlin; Chen, Meng; Wang, Yong; Yu, Qingsong

2014-01-01

Purpose To study the plasma treatment effects on deactivation of oral bacteria seeded on a tooth enamel analogue. Methods A non-thermal atmospheric pressure argon plasma brush was used to treat two different Gram-positive oral bacteria including Lactobacillus acidophilus (L. acidophilus) and Streptococcus mutans (S. mutans). The bacteria were seeded on hydroxyapatite (HA) disks used as tooth enamel analogue with three initial bacterial seeding concentrations: a low inoculum concentration between 2.1×108 and 2.4×108 cfu/mL, a medium inoculum concentration between 9.8×108 and 2.4×109 cfu/mL, and a high inoculum concentration between 1.7×1010 and 3.5×1010 cfu/mL. The bacterial survivability upon plasma exposure was examined in terms of plasma exposure time and oxygen addition into the plasmas. SEM was performed to examine bacterial morphological changes after plasma exposure. Results The experimental data indicated that 13 second plasma exposure time completely killed all the bacteria when initial bacterial seeding density on HA surfaces were less than 6.9×106 cfu/cm2 for L. acidophilus and 1.7×107 cfu/cm2 for S. mutans, which were resulted from low initial seeding inoculum concentration between 2.1×108 and 2.4×108 cfu/mL. Plasma exposure of the bacteria at higher initial bacterial seeding density obtained with high initial seeding inoculum concentration, however, only resulted in ~ 1.5 to 2 log reduction and ~ 2 to 2.5 log reduction for L. acidophilus and S. mutans, respectively. It was also noted that oxygen addition into the argon plasma brush did not affect the plasma deactivation effectiveness. SEM images showed that plasma deactivation mainly occurred with the top layer bacteria, while shadowing effects from the resulting bacterial debris reduced the plasma deactivation of the underlying bacteria. Clinical Significance The experimental results indicate that, with direct contact, nonthermal atmospheric pressure argon plasmas could rapidly and effectively deactivate oral bacteria seeded on HA surfaces and thus could be a promising technique in various dental clinical applications. PMID:25000666

Plasma vaspin concentrations are decreased in acute coronary syndrome, but unchanged in patients without coronary lesions.

PubMed

Zhang, Baowei; Peng, Wenhui; Li, Hailing; Lu, Yuyan; Zhuang, Jianhui; Wang, Ke; Su, Yang; Xu, Yawei

2013-10-01

Previous studies suggested that decreased serum vaspin levels were associated with coronary artery disease (CAD). The present study aimed to investigate the association between plasma vaspin levels and different states of CAD. A total of 162 patients with coronary angiography (CAG) proved that CAD was enrolled. Additional 103 patients complained with "chest discomfort" with negative CAG, and 60 normal subjects were enrolled in this study. The levels of plasma vaspin, adiponectin, clinical parameters, lipid profile and C reactive protein (CRP) were measured. The levels of plasma vaspin were significantly lower in the CAD group (0.47±0.63 μg/L) than those in the healthy group and CAG (-) group (all p<0.001). In CAD group, the pos hoc analysis showed that serum vaspin concentration in acute myocardial infarction group (0.21±0.19 μg/L) was significantly lower than that in the unstable angina pectoris group (0.40±0.37 μg/L) (p=0.012), and serum vaspin concentration in unstable angina pectoris was significantly lower than that in stable angina pectoris group (0.92±0.94 μg/L) (p=0.013). The plasma vaspin concentration was also negatively correlated with the severity of CAD (1-vessel: 0.86±0.90 μg/L; 2-vessel: 0.36±0.39 μg/L; 3-vessel: 0.21±0.16 μg/L). The plasma vaspin concentration in CAG (-) group with "chest discomfort" (1.93±2.57 μg/L) was similar to the healthy control group (2.18±3.49μg/L). The plasma vaspin concentration correlated to the severity of CAD. Furthermore, plasma vaspin has a value of avoiding patients without CAD from unnecessary CAG. © 2013.

Plasma chitinase 3-like 1 is persistently elevated during first month after minimally invasive colorectal cancer resection

PubMed Central

Shantha Kumara, H M C; Gaita, David; Miyagaki, Hiromichi; Yan, Xiaohong; Hearth, Sonali AC; Njoh, Linda; Cekic, Vesna; Whelan, Richard L

2016-01-01

AIM To assess blood chitinase 3-like 1 (CHi3L1) levels for 2 mo after minimally invasive colorectal resection (MICR) for colorectal cancer (CRC). METHODS CRC patients in an Institutional Review Board approved data/plasma bank who underwent elective MICR for whom preoperative (PreOp), early postoperative (PostOp), and 1 or more late PostOp samples [postoperative day (POD) 7-27] available were included. Plasma CHi3L1 levels (ng/mL) were determined in duplicate by enzyme linked immunosorbent assay. RESULTS PreOp and PostOp plasma sample were available for 80 MICR cancer patients for the study. The median PreOp CHi3L1 level was 56.8 CI: 41.9-78.6 ng/mL (n = 80). Significantly elevated (P < 0.001) median plasma levels (ng/mL) over PreOp levels were detected on POD1 (667.7 CI: 495.7, 771.7; n = 79), POD 3 (132.6 CI: 95.5, 173.7; n = 76), POD7-13 (96.4 CI: 67.7, 136.9; n = 62), POD14-20 (101.4 CI: 80.7, 287.4; n = 22), and POD 21-27 (98.1 CI: 66.8, 137.4; n = 20, P = 0.001). No significant difference in plasma levels were noted on POD27-41. CONCLUSION Plasma CHi3L1 levels were significantly elevated for one month after MICR. Persistently elevated plasma CHi3L1 may support the growth of residual tumor and metastasis. PMID:27574553

Clinical signs and hematologic, cytokine, and plasma nitric oxide alterations in response to Strongylus vulgaris infection in helminth-naïve ponies.

PubMed

Hubert, Jeremy D; Seahorn, Thomas L; Klei, Thomas R; Hosgood, Giselle; Horohov, David W; Moore, Rustin M

2004-07-01

The objective of this study was to determine the effect of infection with Strongylus vulgaris on serum cytokines and plasma nitric oxide (NO) concentrations in helminth-naive ponies. Group 1 (n = 21) was given 500 S. vulgaris L3 larvae and group 2 (n = 7) received a saline control. Ponies were monitored daily for clinical signs, and blood was collected for complete blood cell counts and serum cytokines (TNF, IL-1, IL-6) quantification. Group 1 ponies were depressed, anorexic, and febrile for variable periods of time. Plasma NO was increased on day 21 in group 1 and on days 9 and 21 in group 2. Significant increases in total white blood cell counts, fibrinogen, and plasma protein concentrations in group 1 were found. Significant decreases in red blood cell counts and packed cell volume were also noted in group 1. There were no differences in serum cytokines across time in either group of ponies. Despite the lack of proinflammatory cytokine induction with the apparent inflammatory response to S. vulgaris there is evidence of a potential role of NO.