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Sample records for plasma derivatives safety

  1. Human plasma-derived FVIII/VWD concentrate (Biostate): a review of experimental and clinical pharmacokinetic, efficacy and safety data

    PubMed Central

    Harper, Paul; Favaloro, Emmanuel J.; Curtin, Julie; Barnes, Chris; Dunkley, Scott

    2016-01-01

    Human plasma-derived factor VIII/von Willebrand factor complex concentrates are used to control bleeding in patients with von Willebrand disease (VWD) or haemophilia A (HA). The properties of these haemostatic factor concentrates vary widely, which can have significant clinical implications. This review provides an extensive overview of the molecular properties, in addition to pharmacokinetic, efficacy and safety data, and case studies of clinical experience of one such concentrate, Biostate. These data are discussed in the context of various therapeutic applications and compared with other factor concentrate products. Data are presented from data on file from the manufacturer; product information and published experimental and clinical pharmacokinetic, safety and efficacy study data; and example case studies of clinical experience. The data discussed herein demonstrate that Biostate has well-established efficacy profiles in the treatment of patients with VWD or HA, with the control of bleeding rated as ‘excellent’, ‘good’ or ‘moderate’ in >90% of patients. In an immune-tolerance induction setting, 73% of patients achieved a complete response following treatment with Biostate. Biostate was generally well tolerated in patients with HA or VWD, with infrequent minor adverse events reported and no reported cases of clinically relevant thrombosis. PMID:27114741

  2. The efficacy and safety of platelet-rich plasma and adipose-derived stem cells: an update.

    PubMed

    Choi, Jaehoon; Minn, Kyung Won; Chang, Hak

    2012-11-01

    During the past decade, many studies using platelet-rich plasma (PRP) or adipose-derived stem cells (ASCs) have been conducted in various medical fields, from cardiovascular research to applications for corneal diseases. Nonetheless, there are several limitations of practical applications of PRP and ASCs. Most reports of PRP are anecdotal and few include controls to determine the specific role of PRP. There is little consensus regarding PRP production and characterization. Some have reported the development of an antibody to bovine thrombin, which was the initiator of platelet activation. In the case of ASCs, good manufacturing practices are needed for the production of clinical-grade human stem cells, and in vitro expansion of ASCs requires approval of the Korea Food and Drug Administration, such that considerable expense and time are required. Additionally, some have reported that ASCs could have a potential risk of transformation to malignant cells. Therefore, the authors tried to investigate the latest research on the efficacy and safety of PRP and ASCs and report on the current state and regulation of these stem cell-based therapies. PMID:23233882

  3. Plasma nanofabrication and nanomaterials safety

    NASA Astrophysics Data System (ADS)

    Han, Z. J.; Levchenko, I.; Kumar, S.; Yajadda, M. M. A.; Yick, S.; Seo, D. H.; Martin, P. J.; Peel, S.; Kuncic, Z.; Ostrikov, K.

    2011-05-01

    The fast advances in nanotechnology have raised increasing concerns related to the safety of nanomaterials when exposed to humans, animals and the environment. However, despite several years of research, the nanomaterials safety field is still in its infancy owing to the complexities of structural and surface properties of these nanomaterials and organism-specific responses to them. Recently, plasma-based technology has been demonstrated as a versatile and effective way for nanofabrication, yet its health and environment-benign nature has not been widely recognized. Here we address the environmental and occupational health and safety effects of various zero- and one-dimensional nanomaterials and elaborate the advantages of using plasmas as a safe nanofabrication tool. These advantages include but are not limited to the production of substrate-bound nanomaterials, the isolation of humans from harmful nanomaterials, and the effective reforming of toxic and flammable gases. It is concluded that plasma nanofabrication can minimize the hazards in the workplace and represents a safe way for future nanofabrication technologies.

  4. Chinese plasma-derived products supply under the lot release management system in 2007-2011.

    PubMed

    Zhang, Xuejun; Ye, Shengliang; Du, Xi; Yuan, Jing; Zhao, Chaoming; Li, Changqing

    2013-11-01

    In 2007, the Chinese State Food and Drug Administration (SFDA) implemented a management system for lot release of all plasma-derived products. Since then, there have been only a few systematic studies of the blood supply, which is a concern when considering the small amount of plasma collected per capita (approximately 3 L/1000 people). As a result, there may be a threat to the safety of the available blood supply. In this study, we examined the characteristics of the supply of Chinese plasma-derived products. We investigated the reports of lot-released biological products derived from all 8 national or regional regulatory authorities in China from 2007 to 2011. The market supply characteristics of Chinese plasma-derived products were analyzed by reviewing the changes in supply varieties, the batches of lot-released plasma-derived products and the actual supply. As a result, the national regulatory authorities can more accurately develop a specific understanding of the production and quality management information provided by Chinese plasma product manufacturers. The implementation of the lot release system further ensures the clinical validity of the plasma-derived products in China and improves the safety of using plasma-derived products. This work provides an assessment of the future Chinese market supply of plasma-derived products and can function as a theoretical basis for the establishment of hemovigilance. PMID:23856276

  5. Deriving and applying generally applicable safety principles

    SciTech Connect

    Spray, S.D.

    1998-08-01

    The nuclear detonation safety of modern nuclear weapons depends on a coordinated safety theme incorporating three general safety principles: isolation, inoperability, and incompatibility. The success of this approach has encouraged them to study whether these and/or other principles might be useful in other applications. Not surprisingly, no additional first-principles (based on physical laws) have been identified. However, a more widely applicable definition and application of the principle-based approach has been developed, resulting in a selection of strategies that are basically subsets and varied combinations of the more general principles above. However, identification of principles to be relied on is only one step in providing a safe design. As one other important example, coordinating overall architecture and strategy is essential: the authors term this a safety theme.

  6. 86 The Efficacy and Safety of Human Plasma-derived C1-Inhibitor Concentrate Administered for the Treatment of Attacks in Pediatric Patients with Hereditary Angioedema Due to C1-Inhibitor Deficiency

    PubMed Central

    Farkas, Henriette; Csuka, Dorottya; Zotter, Zsuzsanna; Szabó, Erika; Kelemen, Zsuzsanna; Varga, Lilian; Fejes, János; Harmat, George

    2012-01-01

    Background Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a life-threatening, rare disease characterized by recurrent edematous attacks. In 50% of cases, the initial onset of symptoms occurs between 5 and 11 years of age. There are limited data on the emergency treatment of acute episodes in pediatric patients. Our aim was to analyze the efficacy and safety of human plasma-derived C1-INH concentrate in our pediatric patient population with HAE-C1-INH. Methods 50 pediatric patients (23 boys, 27 girls; 45 HAE type I, 5 HAE type II patients) were enrolled. The follow-up period began at the time of diagnosis and ended when the patient turned 18 years old. The indications for the use of C1-INH concentrate were upper airway oedema of any severity; moderate-to-severe abdominal edema; edema of face, neck, or lips and severe edema of the extremities and trunk. Clinical and laboratory data were entered into the Hungarian HAE Registry. Results 152 attacks out of 1392 experienced by 42 patients were treated with C1-INH concentrate (28% of attacks at home and 72% at the clinic). The distribution of C1-INH-treated attacks by location was as follows: 38% subcutaneous, 32% abdominal, 30% upper airway. In all locations, the clinical symptoms were consistently relieved by 500 IU C1-INH concentrate. An additional 500 IU dose of C1-INH concentrate was required in 4 cases only. The symptoms improved within 15 to 60 minutes of drug administration. Time to complete resolution was 24 to 48 hours in subcutaneous edema, 12 to 24 hours in abdominal attacks, and less than 12 hours when the edema involved the upper airways. No progression or recurrence of the attack was observed. Repeated administration did not reduce therapeutic efficacy of the drug. Adverse events did not occur. Transmission of viral infections (HIV, HBV, HBC, Parvo virus B19) was not detected. Comparing the first and last year of follow-up, anti-C1-INH antibodies (IgA, IgG, IgM types) did not show any

  7. Deriving Safety Cases from Automatically Constructed Proofs

    NASA Technical Reports Server (NTRS)

    Basir, Nurlida; Denney, Ewen; Fischer, Bernd

    2009-01-01

    Formal proofs provide detailed justification for the validity of claims and are widely used in formal software development methods. However, they are often complex and difficult to understand, because the formalism in which they are constructed and encoded is usually machine-oriented, and they may also be based on assumptions that are not justified. This causes concerns about the trustworthiness of using formal proofs as arguments in safety-critical applications. Here, we present an approach to develop safety cases that correspond to formal proofs found by automated theorem provers and reveal the underlying argumentation structure and top-level assumptions. We concentrate on natural deduction style proofs, which are closer to human reasoning than resolution proofs, and show how to construct the safety cases by covering the natural deduction proof tree with corresponding safety case fragments. We also abstract away logical book-keeping steps, which reduces the size of the constructed safety cases. We show how the approach can be applied to the proofs found by the Muscadet prover.

  8. Deriving Safety Cases for the Formal Safety Certification of Automatically Generated Code

    NASA Technical Reports Server (NTRS)

    Basir, Nurlida; Denney, Ewen; Basir, Nurlida

    2009-01-01

    We present an approach to systematically derive safety cases for automatically generated code from information collected during a formal, Hoare-style safety certification of the code. This safety case makes explicit the formal and informal reasoning principles, and reveals the top-level assumptions and external dependencies that must be taken into account; however, the evidence still comes from the formal safety proofs. It uses a generic goal-based argument that is instantiated with respect to the certified safety property (i.e., safety claims) and the program. This will be combined with a complementary safety case that argues the safety of the framework itself, in particular the correctness of the Hoare rules with respect to the safety property and the trustworthiness of the certification system and its individual components. Keywords: Automated code generation, Hoare logic, formal code certification, safety case, Goal Structuring Notation.

  9. Using the Tritium Plasma Experiment to evaluate ITER PFC safety. [Plasma-Facing Components

    SciTech Connect

    Longhurst, G.R.; Anderl, R.A. ); Bartlit, J.R. ); Causey, R.A. ); Haines, J.R. )

    1993-01-01

    The Tritium Plasma Experiment was assembled at Sandia National Laboratories, Livermore to investigate interactions between dense plasmas at low energies and plasma-facing component materials. This apparatus has the unique capability of replicating plasma conditions in a tokamak divertor with particle flux densities of 2 [times] 10[sup 19] ions/cm[sup 2] [center dot] s and a plasma temperature of about 15 eV using a plasma that includes tritium. With the closure of the Tritium Research Laboratory at Livermore, the experiment was moved to the Tritium Systems Test Assembly facility at Los Alamos National Laboratory. An experimental program has been initiated there using the Tritium Plasma Experiment to examine safety issues related to tritium in plasma-facing components, particularly the ITER divertor. Those issues include tritium retention and release characteristics, tritium permeation rates and transient times to coolant streams, surface modification and erosion by the plasma, the effects of thermal loads and cycling, and particulate production. A considerable lack of data exists in these areas for many of the materials, especially beryllium, being considered for use in ITER. Not only will basic material behavior with respect to safety issues in the divertor environment be examined, but innovative techniques for optimizing performance with respect to tritium safety by material modification and process control will be investigated. Supplementary experiments will be carried out at the Idaho National Engineering Laboratory and Sandia National Laboratory to expand and clarify results obtained on the Tritium Plasma Experiment.

  10. [Study of plasma and hepatic hydrolysis of nitroxinil derivatives].

    PubMed

    Baziard-Mouysset, G; Alvinerie, M; Galtier, P; Ane-Margail, M; Floch, R; Payard, M

    1996-01-01

    Seven esters derivatives of Nitroxinil were prepared and their structures were assigned by IR and 1H-NMR spectroscopy. The rate of plasma and hepatic hydrolysis were evaluated in vitro in sheep and rabbit. In view of this profile of activity, pivaloyl derivative merits evaluation, in vivo. PMID:8953797

  11. Effect of surface derived hydrocarbon impurities on Ar plasma properties

    SciTech Connect

    Fox-Lyon, Nick; Oehrlein, Gottlieb S.; Godyak, Valery

    2014-05-15

    The authors report on Langmuir probe measurements that show that hydrocarbon surfaces in contact with Ar plasma cause changes of electron energy distribution functions due to the flux of hydrogen and carbon atoms released by the surfaces. The authors compare the impact on plasma properties of hydrocarbon species gasified from an etching hydrocarbon surface with injection of gaseous hydrocarbons into Ar plasma. They find that both kinds of hydrocarbon injections decrease electron density and slightly increase electron temperatures of low pressure Ar plasma. For low percentages of impurities (∼1% impurity in Ar plasma explored here), surface-derived hydrocarbon species and gas phase injected hydrocarbon molecules cause similar changes of plasma properties for the same number of hydrocarbon molecules injected into Ar with a decrease in electron density of ∼4%.

  12. Plasma Distribution in Mercury's Magnetosphere Derived from MESSENGER Magnetometer and Fast Imaging Plasma Spectrometer Observations

    NASA Technical Reports Server (NTRS)

    Korth, Haje; Anderson, Brian J.; Gershman, Daniel J.; Raines, Jim M.; Slavin, James A.; Zurbuchen, Thomas H.; Solomon, Sean C.; McNutt, Ralph L.

    2014-01-01

    We assess the statistical spatial distribution of plasma in Mercury's magnetosphere from observations of magnetic pressure deficits and plasma characteristics by the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft. The statistical distributions of proton flux and pressure were derived from 10months of Fast Imaging Plasma Spectrometer (FIPS) observations obtained during the orbital phase of the MESSENGER mission. The Magnetometer-derived pressure distributions compare favorably with those deduced from the FIPS observations at locations where depressions in the magnetic field associated with the presence of enhanced plasma pressures are discernible in the Magnetometer data. The magnitudes of the magnetic pressure deficit and the plasma pressure agree on average, although the two measures of plasma pressure may deviate for individual events by as much as a factor of approximately 3. The FIPS distributions provide better statistics in regions where the plasma is more tenuous and reveal an enhanced plasma population near the magnetopause flanks resulting from direct entry of magnetosheath plasma into the low-latitude boundary layer of the magnetosphere. The plasma observations also exhibit a pronounced north-south asymmetry on the nightside, with markedly lower fluxes at low altitudes in the northern hemisphere than at higher altitudes in the south on the same field line. This asymmetry is consistent with particle loss to the southern hemisphere surface during bounce motion in Mercury's offset dipole magnetic field.

  13. Deriving plasma densities in tenuous plasma regions, with the spacecraft potential under active control

    NASA Astrophysics Data System (ADS)

    Andriopoulou, M.; Nakamura, R.; Torkar, K.; Baumjohann, W.; Hoelzl, B.

    2015-11-01

    Variations of the floating potential on spacecraft are often used to derive plasma densities, complementing the plasma instrument measurements. All spacecraft of the Cluster mission are equipped with Active Spacecraft POtential Control (ASPOC) instruments that control the spacecraft potential. Although the ASPOC operation increases the accuracy of electric field and plasma measurements, it prevents a direct use of the spacecraft potential variations to derive plasma densities. In this work we develop a new reconstruction method of uncontrolled spacecraft potential from controlled spacecraft potential data and a derived photoelectron curve, using multispacecraft observations. We assume that the same curve governs the plasma environment for the spacecraft with ASPOC on and off. The current work focuses on reconstructions in the magnetotail region. The period that was more extensively studied was the one from August to October 2003, when the spacecraft were close to each other, while results from the periods of August-October 2001, 2002, and 2004, when the Cluster spacecraft had their apogee in the magnetotail region, are also presented. In this way, we investigate how the photoelectron curve varies at different time intervals and also how the reconstruction results are modified when the distance between the spacecraft is increasing. Finally, by using the reconstructed results, we proceed by estimating the plasma densities and we discuss the uncertainties of such estimations. While, on average, spacecraft potential measurements are successfully reconstructed, plasma and solar activity variations on short timescales seem to affect the reconstructions, requiring in some cases more detailed analysis in order to achieve results with higher accuracy. Moreover, there are some limitations while deriving results in very tenuous plasma regions due to increased uncertainties in some of the scientific measurements used there. The results and the methods developed for this work

  14. New Mathematical Derivations Applicable to Safety and Reliability Analysis

    SciTech Connect

    Cooper, J.A.; Ferson, S.

    1999-04-19

    Boolean logic expressions are often derived in safety and reliability analysis. Since the values of the operands are rarely exact, accounting for uncertainty with the tightest justifiable bounds is important. Accurate determination of result bounds is difficult when the inputs have constraints. One example of a constraint is that an uncertain variable that appears multiple times in a Boolean expression must always have the same value, although the value cannot be exactly specified. A solution for this repeated variable problem is demonstrated for two Boolean classes. The classes, termed functions with unate variables (including, but not limited to unate functions), and exclusive-or functions, frequently appear in Boolean equations for uncertain outcomes portrayed by logic trees (event trees and fault trees).

  15. Safety evaluation of neem (Azadirachta indica) derived pesticides.

    PubMed

    Boeke, Sara J; Boersma, Marelle G; Alink, Gerrit M; van Loon, Joop J A; van Huis, Arnold; Dicke, Marcel; Rietjens, Ivonne M C M

    2004-09-01

    The neem tree, Azadirachta indica, provides many useful compounds that are used as pesticides and could be applied to protect stored seeds against insects. However in addition to possible beneficial health effects, such as blood sugar lowering properties, anti-parasitic, anti-inflammatory, anti-ulcer and hepatoprotective effects, also toxic effects are described. In this study we present a review of the toxicological data from human and animal studies with oral administration of different neem-based preparations. The non-aqueous extracts appear to be the most toxic neem-based products, with an estimated safe dose (ESD) of 0.002 and 12.5 microg/kg bw/day. Less toxic are the unprocessed materials seed oil and the aqueous extracts (ESD 0.26 and 0.3 mg/kg bw/day, 2 microl/kg bw/day respectively). Most of the pure compounds show a relatively low toxicity (ESD azadirachtin 15 mg/kg bw/day). For all preparations, reversible effect on reproduction of both male and female mammals seem to be the most important toxic effects upon sub-acute or chronic exposure. From the available data, safety assessments for the various neem-derived preparations were made and the outcomes are compared to the ingestion of residues on food treated with neem preparations as insecticides. This leads to the conclusion that, if applied with care, use of neem derived pesticides as an insecticide should not be discouraged. PMID:15261960

  16. Microwave plasma assisted pyrolysis of refuse derived fuels

    NASA Astrophysics Data System (ADS)

    Khongkrapan, Parin; Thanompongchart, Patipat; Tippayawong, Nakorn; Kiatsiriroat, Tanongkiat

    2014-03-01

    This work combined plasma reactivity and pyrolysis for conversion of solid wastes. Decomposition of refuse derived fuel (RDF) and its combustible components (paper, biomass, and plastic) in an 800 W microwave plasma reactor was investigated at varying argon flow rates of 0.50 to 1.25 lpm for 3 minutes. The characteristic bright light emission of plasma was observed with calculated maximum power density of about 35 W/cm3. The RDF and its components were successfully converted into char and combustible gas. The average char yield was found to be 12-21% of the original mass, with a gross calorific value of around 39 MJ/kg. The yield of the product gas was in the range 1.0-1.7 m3/kg. The combustible gas generated from the pyrolysis of the RDF contained about 14% H2, 66% CO, and 4% CH4 of the detected gas mass, with a heating value of 11 MJ/m3. These products are potentially marketable forms of clean energy.

  17. Deriving Safety Cases from Machine-Generated Proofs

    NASA Technical Reports Server (NTRS)

    Basir, Nurlida; Fischer, Bernd; Denney, Ewen

    2009-01-01

    Proofs provide detailed justification for the validity of claims and are widely used in formal software development methods. However, they are often complex and difficult to understand, because they use machine-oriented formalisms; they may also be based on assumptions that are not justified. This causes concerns about the trustworthiness of using formal proofs as arguments in safety-critical applications. Here, we present an approach to develop safety cases that correspond to formal proofs found by automated theorem provers and reveal the underlying argumentation structure and top-level assumptions. We concentrate on natural deduction proofs and show how to construct the safety cases by covering the proof tree with corresponding safety case fragments.

  18. Current concepts in the prevention of pathogen transmission via blood/plasma-derived products for bleeding disorders.

    PubMed

    Di Minno, Giovanni; Perno, Carlo Federico; Tiede, Andreas; Navarro, David; Canaro, Mariana; Güertler, Lutz; Ironside, James W

    2016-01-01

    The pathogen safety of blood/plasma-derived products has historically been a subject of significant concern to the medical community. Measures such as donor selection and blood screening have contributed to increase the safety of these products, but pathogen transmission does still occur. Reasons for this include lack of sensitivity/specificity of current screening methods, lack of reliable screening tests for some pathogens (e.g. prions) and the fact that many potentially harmful infectious agents are not routinely screened for. Methods for the purification/inactivation of blood/plasma-derived products have been developed in order to further reduce the residual risk, but low concentrations of pathogens do not necessarily imply a low level of risk for the patient and so the overall challenge of minimising risk remains. This review aims to discuss the variable level of pathogenic risk and describes the current screening methods used to prevent/detect the presence of pathogens in blood/plasma-derived products. PMID:26381318

  19. Molecular characterisation of plasma membrane-derived vesicles.

    PubMed

    Antwi-Baffour, Samuel S

    2015-01-01

    Plasma membrane-derived vesicles (PMVs) are released into circulation in response to normal and stress/pathogenic conditions. They are of tremendous significance for the prediction, diagnosis, and observation of the therapeutic success of many diseases. Knowledge of their molecular characteristics and therefore functional properties would contribute to a better understanding of the pathological mechanisms leading to various diseases in which their levels are raised. The review aims at outlining and discussing the molecular characteristics of PMVs in order to bring to the fore some aspects/characteristics of PMVs that will assist the scientific community to properly understand the role of PMVs in various physiological and pathological processes. The review covers PMVs characterisation and discusses how distinct they are from exosomes and endosomes. Also, methods of PMVs analysis, importance of proper PMV level estimation/characterisation, PMVs and their constituents as well as their therapeutic significance are discussed. The review concludes by drawing attention to the importance of further study into the functions of the characteristics discussed which will lead to understanding the general role of PMVs both in health and in disease states. PMID:26259622

  20. Safety assessment of Vitis vinifera (grape)-derived ingredients as used in cosmetics.

    PubMed

    Fiume, Monice M; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2014-01-01

    The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of 24 Vitis vinifera (grape)-derived ingredients and found them safe in the present practices of use and concentration in cosmetics. These ingredients function in cosmetics mostly as skin-conditioning agents, but some function as antioxidants, flavoring agents, and/or colorants. The Panel reviewed the available animal and clinical data to determine the safety of these ingredients. Additionally, some constituents of grapes have been assessed previously for safety as cosmetic ingredients by the Panel, and others are compounds that have been discussed in previous Panel safety assessments. PMID:25297908

  1. Treatment of hereditary angioedema with plasma-derived C1 inhibitor

    PubMed Central

    Prematta, Michael J; Prematta, Tracy; Craig, Timothy J

    2008-01-01

    Background: Plasma-derived C1 inhibitor (C1-INH) concentrate is a treatment option for acute hereditary angioedema (HAE) attacks and is considered the standard-of-care in many countries, although it is not yet available in the United States. Studies are still being conducted to establish its safety and efficacy as required by the FDA. Objective: To review the medical literature to determine if C1-INH concentrate is a safe and effective treatment for acute HAE attacks. Methods: The following keywords were searched in PubMed and OVID: C1 esterase inhibitor, C1-inhibitor, C1 inhibitor, and hereditary angioedema treatment. English-language articles were searched from 1966 to the present to look for studies demonstrating the efficacy and the safety of C1-INH concentrate. Results: The English-language literature search revealed several studies showing significantly improved relief of HAE symptoms with the administration of C1-INH concentrate – many studies demonstrated some improvement of symptoms within 30 minutes. Side effects have been similar to placebo, and no proven cases of viral transmission have occurred in over 20 years. Conclusion: C1-INH concentrate appears to be a very safe and effective treatment option for HAE. PMID:19209279

  2. Safety evaluation of a natural eggshell membrane-derived product.

    PubMed

    Ruff, Kevin J; Endres, John R; Clewell, Amy E; Szabo, James R; Schauss, Alexander G

    2012-03-01

    Natural Eggshell Membrane (NEM®) is a novel dietary ingredient that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy joint and connective tissues. NEM® was evaluated for safety via in vitro and in vivo toxicological studies. This included testing for cytotoxicity, genotoxicity, acute oral toxicity, and 90-day repeated-dose oral toxicity. NEM® did not exhibit any cytotoxic effects at a dose of 100 μg in an in vitro human cell viability assay after incubation for up to 20 h. NEM® did not exhibit any genotoxic effects in an in vitro assay of four strains of histidine-dependent Salmonella typhimurium and one strain of tryptophan-dependent Escherichia coli at a dose of up to 5000 μg/plate. NEM® did not exhibit any signs of acute toxicity in rats at a single oral dose of up to 2000 mg/kg body weight, nor signs of toxicity (via urinalysis, hematology, clinical chemistry, or histopathological evaluation) in rats at a repeated oral dose of up to 2000 mg/kg body weight per day for 90 days. The results of these studies suggest that NEM® may be safe for human consumption. PMID:22245377

  3. Characterization of Al2O3 Supported Nickel Catalysts Derived from RFNon-thermal Plasma Technology

    SciTech Connect

    Jang, Ben W; Helleson, Michael J; Shi, Chunkai; Rondinone, Adam Justin; Schwartz, Viviane; Liang, Chengdu; Overbury, Steven {Steve} H

    2008-01-01

    Catalysts derived from non-thermal plasma techniques have previously shown unusual and highly advantageous catalytic properties including room temperature reduction, unusual metal particle structure and metal-support interactions, and enhanced selectivity and stability. This study focuses on the characterization of Al2O3 supported Ni catalysts derived from the RF non-thermal plasma technique with in-situ XRD, TPR-MS and STEM and on relating the results to the enhanced activity and stability of benzene hydrogenation. The results suggest that catalysts with plasma treatments before impregnation are relatively easier to be reduced and result in better activities under mild reduction conditions. These plasma treatments stabilize the nickel particle sizes of air(B) and H2(B) catalysts at 600 C by slowing down the sintering process. Plasma treatments after the impregnation of precursors, on the other hand, tend to delay the growth of nickel particles below 600 C, forming smaller Ni particles, but with a sudden increase in particle size near 600 C. It suggests that the structure of Ni nitrate and the metal-support interaction have been altered by the plasma treatments. The reduction patterns of plasma 1 treated catalysts are, therefore, changed. The catalyst with a combination plasma treatment demonstrates that the effect of a combination plasma treatment is larger than either the plasma treatment before or after the impregnation alone. Both plasma treatments before and after the impregnation of metal precursor play important roles in modifying supported metal catalysts.

  4. Safety characteristics of options for plasma-facing components for ITER and beyond

    SciTech Connect

    Piet, S.J.; McCarthy, K.A.; Holland, D.F.; Longhurst, G.R.; Merrill, B.J.

    1991-01-01

    Plasma-facing components (PFC) likely dominate the safety hazards of the International Thermonuclear Experimental Reactor (ITER) and post-ITER machines. To gain regulatory approval and for fusion energy to fulfill its ultimate attractive safety and environmental potential, safety must be considered when selecting among PFC options. This paper summarizes current PFC safety information. PFC safety issues fall into seven areas: disruption tolerance, disruption severity, tritium inventory and permeation, accidental energy release, activation/toxin hazards, cooling disturbances, and system issues. RFC options include current ITER mainline options (Be or W coating, C tiles), variants on current ITER options, and liquid metal (LM) divertors. No PFC option that we have examined is free of critical safety concerns. There are also innovative ideas that may improve any PFC's performance -- super-permeable vacuum ducts, helium self-pumping, and gaseous divertors. We conclude with recommendations and a future strategy. 17 refs., 1 fig., 3 tabs.

  5. [Hemorrhagic congenital diseases: What can be the future of plasma-derived products against recombinants?].

    PubMed

    Schved, J-F

    2015-08-01

    Until 1990, congenital hemorrhagic disorders were treated by plasma-derived concentrates. The first recombinant drug, recombinant factor VIII was available after this date and few years later recombinant factor IX could also be proposed to patients. The evolution of market share in France was different between these two drugs: while recombinant factor VIII took a large place in hemophilia A treatment (85%), plasma-derived factor IX represent 50% of the French market. In the next years, the arrival of long-acting antihemophilic factors may lead to the dramatically reduce the amount of plasma-derived antihemophilic factors used to treat hemophilia. For rare bleeding coagulation disorders, plasma-derived concentrates are still widely used, while they are the only concentrates available in most diseases. This situation is unlikely to evolve significantly in the next years. PMID:25933512

  6. Safety assessment of animal- and plant-derived amino acids as used in cosmetics.

    PubMed

    Burnett, Christina; Heldreth, Bart; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2014-01-01

    The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of animal- and plant-derived amino acid mixtures, which function as skin and hair conditioning agents. The safety of α-amino acids as direct food additives has been well established, based on extensive research through acute and chronic dietary exposures and the Panel previously has reviewed the safety of individual α-amino acids in cosmetics. The Panel focused its review on dermal irritation and sensitization data relevant to the use of these ingredients in topical cosmetics. The Panel concluded that these 21 ingredients are safe in the present practices of use and concentration as used in cosmetics. PMID:25323218

  7. [The virological safety and bacterial sterility of a method for fractionating blood plasma proteins with rivanol].

    PubMed

    Zhurina, N A; Shatskaia, T L; Katushkina, N V

    1993-01-01

    The bacterial and virological safety of the method of rivanol fractionation of blood plasma proteins has been evaluated in experiments with samples of donor blood plasma mixed with the suspension of viruses and Escherichia coli used as models. The bacteriostatic action of rivanol and the elimination of bacteriophage and influenza virus from the end product at the stages of rivanol precipitation and adsorption on carbon have been established. PMID:8067072

  8. The role of plasma-derived factor VIII/von Willebrand factor concentrates in the treatment of hemophilia A patients.

    PubMed

    Auerswald, Günter; Spranger, Torsten; Brackmann, Hans-Hermann

    2003-06-01

    Besides preventing bleeding episodes, common goals of the treatment of hemophilia include integrating of patients into a normal social life and optimizing their quality of life. Sufficient amounts of factor VIII (FVIII) concentrates, whether recombinant or plasma-derived, are continuously needed. Guidelines for quality assurance of treatment will be a cornerstone to maintain optimal clinical management of patients especially considering financial aspects. Advances in manufacturing technologies have made possible general availability of modern concentrates for the management of hemophilia A patients. Safety, cost and continuous supply of concentrates must be considered when deciding on a product for replacement therapy. As todays' products have reached an excellent margin of safety with regard to virus transmission, the development and treatment of inhibitors is currently the main concern for physicians and patients. The incidence of inhibitors is influenced by various patient-related factors such as mutation type or severity of the disease. Plasma-derived FVIII concentrates containing von Willebrand factor (VWF) may have clinical advantages over pure FVIII concentrates with regard to inhibitor development and inhibitor eradication. Clinical trials comparing FVIII/VWF concentrates with pure FVIII concentrates are lacking, thus a lower inhibitor incidence has not yet been proven. Data from Germany on immune tolerance induction with FVIII/VWF concentrates indicate higher success rates with these than with pure FVIII concentrates. In addition FVIII/VWF concentrates are the therapy of choice when immune tolerance therapy with pure FVIII products is not successful. PMID:12826531

  9. Histamine-induced airway mucosal exudation of bulk plasma and plasma-derived mediators is not inhibited by intravenous bronchodilators.

    PubMed

    Svensson, C; Alkner, U; Pipkorn, U; Persson, C G

    1994-01-01

    Experimental data suggest the possibility that common bronchodilators, such as the xanthines and beta 2-adrenoceptor agonists, may produce microvascular anti-permeability effects in the subepithelial microcirculation of the airways. In this study, we have examined the effect of bronchodilators given intravenously on exudation of different-sized plasma proteins (albumin and fibrinogen) and the generation of plasma-derived peptides (bradykinins) in human nasal airways challenged with histamine. In a double-blind, crossover, placebo-controlled and randomised trial, 12 normal volunteers were given i.v.infusions of terbutaline sulphate, theophylline and enprofylline to produce therapeutic drug levels. The effect of topical nasal provocation with histamine was closely followed by frequently nasal lavage with saline. The lavage fluid levels of albumin, fibrinogen and bradykinins increased significantly after each histamine provocation. The ratio of albumin-to-fibrinogen in plasma and the lavage fluid was 24 and 56, respectively, indicating that topical histamine provocation induced a largely non-sieved flux of macromolecules across the endothelial-epithelial barriers. The systemically administered drugs did not affect the nasal symptoms (sneezing, secretion and blockage), nor did they significantly reduce the levels of plasma proteins and plasma-derived mediators in the nasal lavage fluids. The present data suggest that systemic xanthines and beta 2-adrenoceptor agonists, at clinically employed plasma levels, may not affect the microvascular (and epithelial) exudative permeability and the bradykinin forming capacity of human airways. PMID:8005188

  10. Scale analysis of equatorial plasma irregularities derived from Swarm constellation

    NASA Astrophysics Data System (ADS)

    Xiong, Chao; Stolle, Claudia; Lühr, Hermann; Park, Jaeheung; Fejer, Bela G.; Kervalishvili, Guram N.

    2016-07-01

    In this study, we investigated the scale sizes of equatorial plasma irregularities (EPIs) using measurements from the Swarm satellites during its early mission and final constellation phases. We found that with longitudinal separation between Swarm satellites larger than 0.4°, no significant correlation was found any more. This result suggests that EPI structures include plasma density scale sizes less than 44 km in the zonal direction. During the Swarm earlier mission phase, clearly better EPI correlations are obtained in the northern hemisphere, implying more fragmented irregularities in the southern hemisphere where the ambient magnetic field is low. The previously reported inverted-C shell structure of EPIs is generally confirmed by the Swarm observations in the northern hemisphere, but with various tilt angles. From the Swarm spacecrafts with zonal separations of about 150 km, we conclude that larger zonal scale sizes of irregularities exist during the early evening hours (around 1900 LT).

  11. Safety Assessment of Panax spp Root-Derived Ingredients as Used in Cosmetics.

    PubMed

    Becker, Lillian C; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2015-01-01

    The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 13 Panax spp root-derived ingredients as used in cosmetics. Panax "spp" indicates that multiple species within the genus are used in cosmetics, but not all species within that genus. Four species are being considered in this safety assessment. These ingredients function mostly as skin-conditioning agents-miscellaneous, fragrance ingredients, skin-conditioning agents-humectant, skin-conditioning agents-emollient, and cosmetic astringents. The Panel reviewed available data related to these ingredients and addressed the issue of pulegone, a constituent of these ingredients and other ingredients, such as peppermint oil. The Panel concluded that these Panax spp root-derived ingredients are safe in the practices of use and concentration as given in this safety assessment. PMID:26684797

  12. Assessment of the safety of foods derived from genetically modified (GM) crops.

    PubMed

    König, A; Cockburn, A; Crevel, R W R; Debruyne, E; Grafstroem, R; Hammerling, U; Kimber, I; Knudsen, I; Kuiper, H A; Peijnenburg, A A C M; Penninks, A H; Poulsen, M; Schauzu, M; Wal, J M

    2004-07-01

    This paper provides guidance on how to assess the safety of foods derived from genetically modified crops (GM crops); it summarises conclusions and recommendations of Working Group 1 of the ENTRANSFOOD project. The paper provides an approach for adapting the test strategy to the characteristics of the modified crop and the introduced trait, and assessing potential unintended effects from the genetic modification. The proposed approach to safety assessment starts with the comparison of the new GM crop with a traditional counterpart that is generally accepted as safe based on a history of human food use (the concept of substantial equivalence). This case-focused approach ensures that foods derived from GM crops that have passed this extensive test-regime are as safe and nutritious as currently consumed plant-derived foods. The approach is suitable for current and future GM crops with more complex modifications. First, the paper reviews test methods developed for the risk assessment of chemicals, including food additives and pesticides, discussing which of these methods are suitable for the assessment of recombinant proteins and whole foods. Second, the paper presents a systematic approach to combine test methods for the safety assessment of foods derived from a specific GM crop. Third, the paper provides an overview on developments in this area that may prove of use in the safety assessment of GM crops, and recommendations for research priorities. It is concluded that the combination of existing test methods provides a sound test-regime to assess the safety of GM crops. Advances in our understanding of molecular biology, biochemistry, and nutrition may in future allow further improvement of test methods that will over time render the safety assessment of foods even more effective and informative. PMID:15123382

  13. Amended safety assessment of Hypericum perforatum-derived ingredients as used in cosmetics.

    PubMed

    Becker, Lillian C; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2014-01-01

    The Cosmetic Ingredient Review Expert Panel (Panel) has issued an amended safety assessment of 7 Hypericum perforatum-derived ingredients as used in cosmetics. A common name for this plant is St John wort. These ingredients function in cosmetics as skin-conditioning agents-miscellaneous and antimicrobial agents. The Panel reviewed relevant animal and human data related to the H perforatum-derived ingredients. Because formulators may use more than 1 botanical ingredient in a formulation, caution was urged to avoid levels of toxicological concern for constituent chemicals and impurities. The Panel concluded that H perforatum-derived ingredients were safe as cosmetic ingredients in the practices of use and concentration as described in this safety assessment. PMID:25297909

  14. Plasma processes for producing silanes and derivatives thereof

    DOEpatents

    Laine, Richard M; Massey, Dean Richard; Peterson, Peter Young

    2014-03-25

    The invention is generally related to process for generating one or more molecules having the formula Si.sub.xH.sub.y, Si.sub.xD.sub.y, Si.sub.xH.sub.yD.sub.z, and mixtures thereof, where x,y and z are integers .gtoreq.1, H is hydrogen and D is deuterium, such as silane, comprising the steps of: providing a silicon containing material, wherein the silicon containing material includes at least 20 weight percent silicon atoms based on the total weight of the silicon containing material; generating a plasma capable of vaporizing a silicon atom, sputtering a silicon atom, or both using a plasma generating device; and contacting the plasma to the silicon containing material in a chamber having an atmosphere that includes at least about 0.5 mole percent hydrogen atoms and/or deuterium atoms based on the total moles of atoms in the atmosphere; so that a molecule having the formula Si.sub.xH.sub.y; (e.g., silane) is generated. The process preferably includes a step of removing one or more impurities from the Si.sub.xH.sub.y (e.g., the silane) to form a clean Si.sub.xH.sub.y, Si.sub.xD.sub.y, Si.sub.xH.sub.yD.sub.z (e.g., silane). The process may also include a step of reacting the Si.sub.xH.sub.y, Si.sub.xD.sub.y, Si.sub.xH.sub.yD.sub.z (e.g., the silane) to produce a high purity silicon containing material such as electronic grade metallic silicon, photovoltaic grade metallic silicon, or both.

  15. Plasma treated with methylene blue and light: clinical efficacy and safety profile.

    PubMed

    Lozano, Miguel; Cid, Joan; Müller, Thomas H

    2013-10-01

    Methylene blue (MB) was the first method developed for pathogen inactivation of a labile blood component that was introduced in 1991. MB and light (MBL) inactivates most lipid-enveloped viruses and those non-enveloped are, in general, resistant. MBL treatment affects several coagulation factors, most noticeably fibrinogen and factor VIII with a loss of approximately 30%. Using endogenous thrombin potential, a global hemostasis evaluation, MBL treatment of plasma resulted in a 7% to 10% of reduction in thrombin potential. Although, originally, the scientific evidence of its efficacy and safety were scarce, the 4.4 million of units transfused have provided a wide body of evidence of its efficacy and safety in most of clinical situations. Nevertheless, some doubts have arisen about the efficacy of MBL plasma when used as a replacement solution for plasma exchange in the treatment of patients suffering from TTP. Probably only randomized controlled trials would provide definite evidence to clarify this point. Reports of severe allergic reactions in a few patients receiving MBL plasma have provoked the recent decision to remove the product from the market in France. Interestingly hemovigilance data in countries such as the same France, Spain, and United Kingdom have not corroborated an increase in severe allergic reaction. Close monitoring of the patients receiving plasma and suffering from allergic reactions and reporting to hemovigilance schemes hopefully will provide the needed data to definitely establish the exact risk of this complication for MBL vs other types of plasma. PMID:24075476

  16. Safety Assessment of Cucumis sativus (Cucumber)-Derived Ingredients as Used in Cosmetics.

    PubMed

    Fiume, Monice M; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2014-05-26

    The CIR Expert Panel assessed the safety of 6 Cucumis sativus (cucumber)-derived ingredients and found them safe in cosmetic formulations in the present practices of use and concentration. These ingredients are reported to function in cosmetics as skin-conditioning agents. Cucumber is a commonly consumed food with no history of significant adverse effects, suggesting that its ingredients should not pose any major safety issues following oral exposure. This assessment focused on the dermal exposure to the low concentrations of these ingredients as used in cosmetics. Some of the constituents of cucumbers have been assessed previously for safe use as cosmetic ingredients. PMID:24861368

  17. Derivation of stochastic differential equations for scrape-off layer plasma fluctuations from experimentally measured statistics

    SciTech Connect

    Mekkaoui, A.

    2013-01-15

    A stochastic differential equation for intermittent plasma density dynamics in magnetic fusion edge plasma is derived, which is consistent with the experimentally measured gamma distribution and the theoretically expected quadratic nonlinearity. The plasma density is driven by a multiplicative Wiener process and evolves on the turbulence correlation time scale, while the linear growth is quadratically damped by the fluctuation level. The sensitivity of intermittency to the nonlinear dynamics is investigated by analyzing the nonlinear Langevin representation of the beta process, which leads to a root-square nonlinearity.

  18. Edge safety factor at the onset of plasma disruption during VDEs in JT-60U

    NASA Astrophysics Data System (ADS)

    Sugihara, Masayoshi; Lukash, Victor; Khayrutdinov, Rustam; Neyatani, Yuzuru

    2004-10-01

    Detailed examinations of the value of the edge safety factor (qa) at the onset of thermal quench (TQ) during intentional vertical displacement event (VDE) experiments in JT-60U are carried out using two different reconstruction methods, FBI/FBEQU and DINA. The results from the two methods are very similar and show that the TQ occurs when the qa value is in the range between 1.5 and 2. This result suggests that the predictive simulations for VDEs should be performed within this range of q to examine the subsequent differences in the halo currents, plasma movement and other plasma behaviour during the current quench.

  19. Response to "Comment on ' A New Derivation of the Plasma Susceptibility Tensor for a Hot Magnetized Plasma Without Infinite Sums of Products of Bessel Functions'

    SciTech Connect

    Qin, Hong; Phillips, Cynthia K.; Davidson, Ronald C.

    2008-02-20

    We welcome the Comment by Lerche et al on our recent paper titled "A new derivation of the plasma susceptibility tensor for a hot magnetized plasma without infinite sums of products of Bessel functions." The Comment brings up additional historical facts about previous research on the infinite sums of products of Bessel functions appearing in the plasma susceptibility.

  20. A strategy to ensure safety of stem cell-derived retinal pigment epithelium cells.

    PubMed

    Choudhary, Parul; Whiting, Paul John

    2016-01-01

    Cell replacement and regenerative therapy using embryonic stem cell-derived material holds promise for the treatment of several pathologies. However, the safety of this approach is of prime importance given the teratogenic potential of residual stem cells, if present in the differentiated cell product. Using the example of embryonic stem cell-derived retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration, we present a novel strategy for ensuring the absence of stem cells in the RPE population. Based on an unbiased screening approach, we identify and validate the expression of CD59, a cell surface marker expressed on RPE but absent on stem cells. We further demonstrate that flow sorting on the basis of CD59 expression can effectively purify RPE and deplete stem cells, resulting in a population free from stem cell impurity. This purification helps to ensure removal of stem cells and hence increases the safety of cells that may be used for clinical transplantation. This strategy can potentially be applied to other pluripotent stem cell-derived material and help mitigate concerns of using such cells for therapy. PMID:27590276

  1. Low plasma concentrations of diet-derived antioxidants in association with microalbuminuria in Indigenous Australian populations.

    PubMed

    Rowley, Kevin; O'Dea, Kerin; Su, Qing; Jenkins, Alicia J; Best, James D

    2003-11-01

    Microalbuminuria is a risk factor for renal and cardiovascular diseases. Oxidant stress may contribute to vascular disease risk by promoting damage to renal and vascular tissues. This study examined the associations of plasma levels of diet-derived antioxidants with albuminuria in Australian population groups at high risk of renal and cardiovascular disease. Data on microalbuminuria and diet-derived plasma antioxidants were drawn from results of cross-sectional community-based risk factor surveys of Aboriginal and Torres Strait Islander peoples (n =698, 15 years and older). Prevalence of microalbuminuria ranged from 17-21%. After adjustment for age, gender, body mass index, diabetes, smoking status, plasma lipids and blood pressure, microalbuminuria was associated with significantly lower plasma concentrations of lycopene (-29%; P <0.001), beta-carotene (-22%; P <0.001), alpha-carotene (-22%; P <0.001) and cryptoxanthin (-17%; P <0.001) compared with normalbuminuric persons. Significant associations of microalbuminuria with plasma concentrations of alpha-tocopherol, retinol, lutein plus zeaxanthin and homocysteine were absent. The data are consistent with a protective effect of diets rich in carotenoids on vascular endothelium and/or renal tissues, and support the need for interventions to address affordable food supplies and dietary quality among Indigenous Australians. PMID:12826019

  2. Derivation of electrostatic Korteweg-deVries equation in fully relativistic two-fluid plasmas

    SciTech Connect

    Lee, Nam C.

    2008-08-15

    A second order Korteweg-deVries (KdV) equation that describes the evolution of nonlinear electrostatic waves in fully relativistic two-fluid plasmas is derived without any assumptions restricting the magnitudes of the flow velocity and the temperatures of each species. In the derivation, the positive and negative species of plasmas are treated with equal footings, not making any species specific assumptions. Thus, the resulting equation, which is expressed in transparent form symmetric in particle species, can be applied to any two-fluid plasmas having arbitrarily large flow velocity and ultrarelativistically high temperatures. The phase velocity of the nonlinear electrostatic waves found in this paper is shown to be related to the flow velocity and the acoustic wave velocity through the Lorentz addition law of velocities, revealing the relativistic nature of the formulation in the present study. The derived KdV equation is applied to some limiting cases, and it is shown that it can be reduced to existing results in nonrelativistic plasmas, while there are some discrepancies from the results in the weak relativistic approximations.

  3. Human immunodeficiency virus type 1 (HIV-1) derived vectors: safety considerations and controversy over therapeutic applications.

    PubMed

    Romano, Gaetano; Claudio, Pier Paolo; Tonini, Tiziana; Giordano, Antonio

    2003-01-01

    The latest generation of lentiviral vectors based on HIV-1 is one of the most efficient tools for gene transduction of mammalian cells. However, the possible employment of HIV-based vectors in clinical trials is a very controversial issue, mainly due to safety and ethical concerns. HIV-1 is a lethal pathogenic agent, which induces AIDS. Genetic vectors must derive either from viruses that are not pathogenic in humans, or that eventually just cause mild illnesses. Patients exposed to HIV-based vectors will test seropositive to certain components of HIV-1. In addition, there might be other possible adverse effects in patients that cannot be predicted, as many aspects of the pathogenesis of AIDS have not been completely understood yet. On these grounds, it seems necessary to improve the design of other lentiviral vectors, which derive from viruses that are not pathogenic in humans and are distantly related to primate retroviridae. PMID:14693483

  4. Electromagnetic Safety of Spacecraft During Active Experiments with the Use of Plasma Accelerators and Ion Injectors

    NASA Astrophysics Data System (ADS)

    Plokhikh, Andrey; Popov, Garri; Shishkin, Gennady; Antropov, Nikolay; Vazhenin, Nikolay; Soganova, Galina

    electromagnetic emission of stationary and pulsed plasma injectors and of the electric propulsions developed on their basis are discussed. Predictive estimates are presented for the influence of originating electromagnetic fields and emissions on the electromagnetic safety of spacecraft and its systems and for the reliability of communication with ground command and tracking stations, and recommendations are given on the reduction of destructive effects. 1. S. Avdyushin, I. Podgorny, G. Popov, A. Porotnikov, "Plasma Accelerator Use for Studying Physical Processes in Space." Plasma Accelerators and Ion Injectors, Nauka, 1984. 2. A. Plokhikh, "Peculiarities of Radio Measurements in the Metal Vacuum Chambers." Vestnik moskovskogo aviatsionnogo instituta. v. 11, No. 2, 2004, pp. 66-78.

  5. Infectious dengue vesicles derived from CD61+ cells in acute patient plasma exhibited a diaphanous appearance

    PubMed Central

    Hsu, Alan Yi-Hui; Wu, Shang-Rung; Tsai, Jih-Jin; Chen, Po-Lin; Chen, Ya-Ping; Chen, Tsai-Yun; Lo, Yu-Chih; Ho, Tzu-Chuan; Lee, Meed; Chen, Min-Ting; Chiu, Yen-Chi; Perng, Guey Chuen

    2015-01-01

    The levels of neutralizing antibody to a pathogen are an effective indicator to predict efficacy of a vaccine in trial. And yet not all the trial vaccines are in line with the theory. Using dengue virus (DENV) to investigate the viral morphology affecting the predictive value, we evaluated the viral morphology in acute dengue plasma compared to that of Vero cells derived DENV. The virions in plasma were infectious and heterogeneous in shape with a “sunny-side up egg” appearance, viral RNA was enclosed with CD61+ cell-derived membrane interspersed by the viral envelope protein, defined as dengue vesicles. The unique viral features were also observed from ex vivo infected human bone marrow. Dengue vesicles were less efficiently neutralized by convalescent patient serum, compared to virions produced from Vero cells. Our results exhibit a reason why potencies of protective immunity fail in vivo and significantly impact dengue vaccine and drug development. PMID:26657027

  6. Identification and quantification of novel cranberry-derived plasma and urinary (poly)phenols.

    PubMed

    Feliciano, Rodrigo P; Boeres, Albert; Massacessi, Luca; Istas, Geoffrey; Ventura, M Rita; Nunes Dos Santos, Cláudia; Heiss, Christian; Rodriguez-Mateos, Ana

    2016-06-01

    Cranberries are a rich source of (poly)phenols, in particular proanthocyanidins, anthocyanins, flavonols, and phenolic acids. However, little is known about their bioavailability in humans. We investigated the absorption, metabolism, and excretion of cranberry (poly)phenols in plasma and urine of healthy young men after consumption of a cranberry juice (787 mg (poly)phenols). A total of 60 cranberry-derived phenolic metabolites were identified using UPLC-Q-TOF-MS analysis with authentic standards. These included sulfates of pyrogallol, valerolactone, benzoic acids, phenylacetic acids, glucuronides of flavonols, as well as sulfates and glucuronides of cinnamic acids. The most abundant plasma metabolites were small phenolic compounds, in particular hippuric acid, catechol-O-sulfate, 2,3-dihydroxybenzoic acid, phenylacetic acid, isoferulic acid, 4-methylcatechol-O-sulfate, α-hydroxyhippuric acid, ferulic acid 4-O-sulfate, benzoic acid, 4-hydroxyphenyl acetic acid, dihydrocaffeic acid 3-O-sulfate, and vanillic acid-4-O-sulfate. Some benzoic acids, cinnamic acids, and flavonol metabolites appeared in plasma early, at 1-2 h post-consumption. Others such as phenylacetic acids, benzaldehydes, pyrogallols, catechols, hippuric and dihydrocinnamic acid derivatives appear in plasma later (Tmax 4-22 h). The 24 h urinary recovery with respect to the amount of (poly)phenols consumed was 6.2%. Our extensive description of the bioavailability of cranberry (poly)phenols lays important groundwork necessary to start understanding the fate of these compounds in humans. PMID:26836705

  7. Gastroprotective Efficacy and Safety Evaluation of Scoparone Derivatives on Experimentally Induced Gastric Lesions in Rodents

    PubMed Central

    Son, Dong Ju; Lee, Gyung Rak; Oh, Sungil; Lee, Sung Eun; Choi, Won Sik

    2015-01-01

    This study investigated the gastroprotective efficacy of synthesized scoparone derivatives on experimentally induced gastritis and their toxicological safety. Six scoparone derivatives were synthesized and screened for gastroprotective activities against HCl/ethanol- and indomethacin-induced gastric ulcers in rats. Among these compounds, 5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin were found to have gastroprotective activity greater than the standard drug rebamipide; 6-methoxy-7,8-methylenedioxycoumarin, 6-methoxy-7,8-(1-methoxy)-methylenedioxycoumarin, 6,7-methylenedioxycoumarin, and 6,7-(1-methoxy)-methylenedioxycoumarin were found to be equipotent or less potent that of rebamipide. Pharmacological studies suggest that the presence of a methoxy group at position C-5 or C-8 of the scoparone’s phenyl ring significantly improves gastroprotective activity, whereas the presence of a dioxolane ring at C-6, C-7, or C-8 was found to have decreased activity. In order to assess toxicological safety, two of the potent gastroprotective scoparone derivatives—5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin—were examined for their acute toxicity in mice as well as their effect on cytochrome P450 (CYP) enzyme activity. These two compounds showed low acute oral toxicity in adult male and female mice, and caused minimal changes to CYP3A4 and CYP2C9 enzyme activity. These results indicate that compared to other scoparone derivatives, 5,6,7-trimethoxycoumarin and 6,7,8-trimethoxycoumarin can improve gastroprotective effects, and they have low toxicity and minimal effects on drug-metabolizing enzymes. PMID:25781220

  8. Plasma distribution of tetraphenylporphyrin derivatives relevant for Photodynamic Therapy: importance and limits of hydrophobicity.

    PubMed

    Chauvin, Benoît; Iorga, Bogdan I; Chaminade, Pierre; Paul, Jean-Louis; Maillard, Philippe; Prognon, Patrice; Kasselouri, Athena

    2013-02-01

    In the course of a Photodynamic Therapy (PDT) protocol, disaggregation of the sensitizer upon binding to plasma proteins and lipoproteins is one of the first steps following intravenous administration. This step governs its subsequent biodistribution and has even been evoked as possibly orientating mechanism of tumor destruction. It is currently admitted as being mainly dependent on sensitizer's hydrophobicity. In this context, as far as glycoconjugation of meso-tetraphenylporphyrin (TPP) macrocycle, a promising strategy to improve targeting of retinoblastoma cells confers to the sensitizer an amphiphilic character, we have studied the effect of this strategy on binding to plasma proteins and lipoproteins. With the exception of the majoritary protein binding (more than 80%) of more hydrophilic para-tetraglycoconjugated derivatives, high density lipoproteins (HDL) appear as main plasma carriers of the other amphiphilic glycoconjugated photosensitizers. This HDL-binding is a combined result of binding affinities (logKa ranging from 4.90 to 8.77 depending on the carrier and the TPP derivative considered) and relative plasma concentrations of the different carriers. Evaluation of binding affinities shows that if hydrophobicity can account for LDL- and HDL-affinities, it is not the case for albumin-affinity. Molecular docking simulations show that, if interactions are mainly of hydrophobic nature, polar interactions such as hydrogen bonds are also involved. This combination of interaction modalities should account for the absence of clear relationship between albumin-affinity and hydrophobicity. Taken together, our findings clarify the importance, but also the limits, of hydrophobicity's role in structure-plasma distribution relationship. PMID:23089311

  9. Plasma native and peptidase-derivable Met-enkephalin responses to restraint stress in rats. Adaptation to repeated restraint.

    PubMed Central

    Pierzchala, K; Van Loon, G R

    1990-01-01

    Met-enkephalin and related proenkephalin A-derived peptides circulate in plasma at picomolar concentration as free, native pentapeptide and at nanomolar concentration in cryptic forms. We have optimized conditions for measurement of immunoreactive Met-enkephalin in plasma and for generation by trypsin and carboxypeptidase B of much greater amounts of total peptidase-derivable Met-enkephalin in plasma of rats, dogs, and humans. Free Met-enkephalin (11 pM) is constituted by native pentapeptide and its sulfoxide. Characterization of plasma total Met-enkephalin derived by peptidic hydrolysis revealed a small amount (38 pM) of Met-enkephalin associated with peptides of molecular mass less than 30,000 D, and probably derived from proenkephalin A, but much larger amounts of Met-enkephalin associated with albumin (1.2 nM) and with a globulin-sized protein (2.8 nM). Thus, plasma protein precursors for peptidase-derivable Met-enkephalin differ structurally and chemically from proenkephalin A. Met-enkephalin generated from plasma by peptidic hydrolysis showed naloxone-reversible bioactivity comparable to synthetic Met-enkephalin. Prolonged exposure of adult, male rats to restraint stress produced biphasic plasma responses, with peaks occurring at 30 s and 30 min in both free native and total peptidase-derivable Met-enkephalin. Repeated daily exposure to this 30-min stress resulted in adaptive loss of responses of both forms to acute restraint. Initial plasma responses of Met-enkephalin paralleled those of epinephrine and norepinephrine, but subsequently showed divergence of response. In conclusion, Met-enkephalin circulates in several forms, some of which may be derived from proteins other than proenkephalin A, and plasma levels of both free native, and peptidase-derivable Met-enkephalin are modulated physiologically. PMID:2312729

  10. Analyses of substantially different plasma current densities and safety factors reconstructed from magnetic diagnostics data

    NASA Astrophysics Data System (ADS)

    Zaitsev, F. S.; Kostomarov, D. P.; Suchkov, E. P.; Drozdov, V. V.; Solano, E. R.; Murari, A.; Matejcik, S.; Hawkes, N. C.; Contributors, JET-EFDA

    2011-10-01

    The problem of plasma current density and safety factor reconstruction using magnetic field measurements is considered. In the traditional formulation, the problem is strongly ill-posed. In particular, substantially different current densities and safety factors can be equally well attributed to the same set of measurements, given their experimental errors. In other words, the problem can be strongly unstable with respect to the input data. Different constraints are used in practice to make the problem more stable. This paper presents an accurate mathematical formulation of the inverse problem and its variants. A numerical algorithm is provided, which permits us to study the stability with respect to variations in the input data, to find all substantially different solutions, or to prove their absence, and to determine the confidence intervals of the reconstructions. The proposed method also allows establishing the maximum error for a given diagnostic (additional constraint), below which the diagnostic efficiently extracts one solution among several substantially different ones. Examples of very different current density and safety factor reconstructions for measurements with finite accuracy are presented for the original formulation of the inverse problem. Cases of MAST, JET and ITER-like plasmas are considered. It is shown that including the motional Stark effect (MSE) measurements as a constraint, provided the accuracy of MSE measurements is sufficient, allows identifying one solution among several very different ones, obtained without such a constraint. The maximum MSE diagnostics error for efficient identification of this solution is estimated for JET. The approach of this paper can be used for a wide range of ill-posed problems in physics and can help in selecting additional conditions, which can identify the most likely solution among several.

  11. New perspectives on dietary-derived treatments and food safety-antinomy in a new era.

    PubMed

    Pan, Si-Yuan; Gao, Si-Hua; Lin, Rui-Chao; Zhou, Shu-Feng; Dong, Hong-Guan; Tang, Min-Ke; Yu, Zhi-Ling; Ko, Kam-Ming

    2015-01-01

    Despite the advances in science and technology and wide use of chemical drugs, dietary intervention (or food therapy) remains useful in preventing or treating many human diseases. A huge body of evidence shows that the dietary pattern or habit is also an important contributing factor to the development of chronic diseases such as hypertension, type 2 diabetes, hyperlipidemia, and cancers. In recent years, over-the-counter health foods, nutraceuticals, and plant-derived medicinal products have been gaining popularity all over the world, particularly in developed countries. Unfortunately, owing to the contamination with various harmful substances in foods and the presence of toxic food components, food-borne diseases have also become increasingly problematic. Incidents of food poisonings or tainted food have been increasing worldwide, particularly in China and other developing countries. Therefore, the government should put in a greater effort in enforcing food safety by improving the surveillance mechanism and exerting highest standards of quality control for foods. PMID:24915382

  12. Mechanism of transfer of LDL-derived free cholesterol to HDL subfractions in human plasma

    SciTech Connect

    Miida, T.; Fielding, C.J.; Fielding, P.E. )

    1990-11-01

    The transfer of ({sup 3}H)cholesterol in low-density lipoprotein (LDL) to different high-density lipoprotein (HDL) species in native human plasma was determined by using nondenaturing two-dimensional electrophoresis. Transfer from LDL had a t{sub 1/2} at 37{degree}C of 51 {plus minus} 8 min and an activation energy of 18.0 kCal mol{sup {minus}1}. There was unexpected specificity among HDL species as acceptors of LDL-derived labeled cholesterol. The largest fraction of the major {alpha}-migrating class (HDL{sub 2b}) was the major initial acceptor of LDL-derived cholesterol. Kinetic analysis indicated a rapid secondary transfer from HDL{sub 2b} to smaller {alpha}HDL (particularly HDL{sub 3}) driven enzymatically by the lecithin-cholesterol acyltransferase reaction. Rates of transfer among {alpha}HDL were most rapid from the largest {alpha}HDL fraction (HDL{sub 2b}), suggesting possible protein-mediated facilitation. Simultaneous measurements of the transport of LDL-derived and cell-derived isotopic cholesterol indicated that the former preferably utilized the {alpha}HDL pathyway, with little label in pre-{beta}HDL. The same experiments confirmed earlier data that cell-derived cholesterol is preferentially channeled through pre-{beta}HDL. The authors suggest that the functional heterogeneity of HDL demonstrated here includes the ability to independently process cell- and LDL-derived free cholesterol.

  13. Derivation of safety factors for setting harvest quotas on adult walleyes from past estimates of abundance

    USGS Publications Warehouse

    Hansen, Michael J.; Staggs, Michael D.; Hoff, Michael H.

    1991-01-01

    Past population estimates of adult walleyes Stizostedion vitreum can be used to set harvest quotas, provided that temporal variability in abundance of adult walleyes is accounted for. We used a long-term data set from Escanaba Lake, Wisconsin, to evaluate the accuracy of past population estimates for setting current-year quotas for adult walleyes. The results from Escanaba Lake were corroborated by comparison with other lakes where adult walleye abundance was estimated in more than 1 year. The accuracy of estimates of adult walleye abundance declined over time from the year the estimate was obtained to the year it was used to set a harvest quota. We derived safety factors for application to past estimates of population size; these factors limit the occurrence of an exploitation rate exceeding the maximum sustainable rate (35%) to approximately 1 in 40. These safety factors declined from 35% for 1-year-old estimates to less than 20% for 10-year-old estimates.

  14. Safety and toxicological evaluation of Aflapin: a novel Boswellia-derived anti-inflammatory product.

    PubMed

    Krishnaraju, A V; Sundararaju, D; Vamsikrishna, U; Suryachandra, R; Machiraju, G; Sengupta, K; Trimurtulu, G

    2010-11-01

    Boswellia serrata gum resin has been used for treatment of various ailments in different cultures for thousands of years. Aflapin(®) is a novel synergistic composition derived from B. serrata gum resin (Indian Patent Application No. 2229/CHE/2008). Aflapin is significantly better as an anti-inflammatory agent compared to the Boswellia extracts presently available in the market. To assess the safety of Aflapin, a battery of acute and sub-acute toxicity studies were conducted in various animal models according to the OECD test guidelines. The acute oral LD50 of Aflapin was greater than 5000 mg/kg in female Sprague Dawley (SD) rats. Acute dermal LD50 of Aflapin was greater than 2000 mg/kg in SD rats. A primary dermal irritation study conducted using New Zealand White rabbits indicated that Aflapin is non-irritating to skin. Aflapin caused minimal ocular irritation in a primary eye irritation test conducted on New Zealand Albino rabbits. A repeat dose 28-day sub-acute oral toxicity study in SD rats demonstrated no significant signs of toxicity. Various evaluations including hematology, clinical chemistry, gross necropsy, and histopathology did not show any significant adverse changes. The NOAEL of Aflapin was found to be greater than 2500 mg/kg body weight. These studies demonstrate broad spectrum safety of Aflapin in animal models. PMID:20874664

  15. The postprandial plasma rye fingerprint includes benzoxazinoid-derived phenylacetamide sulfates.

    PubMed

    Hanhineva, Kati; Keski-Rahkonen, Pekka; Lappi, Jenni; Katina, Kati; Pekkinen, Jenna; Savolainen, Otto; Timonen, Oskari; Paananen, Jussi; Mykkänen, Hannu; Poutanen, Kaisa

    2014-07-01

    The bioavailability of whole-grain rye-derived phytochemicals has not yet been comprehensively characterized, and different baking and manufacturing processes can modulate the phytochemical composition of breads and other rye products. The aim of our study was to find key differences in the phytochemical profile of plasma after the consumption of 3 breads containing rye bran when compared with a plain white wheat bread control. Plasma metabolite profiles of 12 healthy middle-aged men and women were analyzed using LC quadrupole time-of-flight mass spectrometry metabolomics analysis while fasting and at 60 min, 120 min, 240 min, and 24 h after consuming a meal that contained either 100% whole-grain sourdough rye bread or white wheat bread enriched with native unprocessed rye bran or bioprocessed rye bran. White wheat bread was used as the control. The meals were served in random order after a 12-h overnight fast, with at least 3 d between each occasion. Two sulfonated phenylacetamides, hydroxy-N-(2-hydroxyphenyl) acetamide and N-(2-hydroxyphenyl) acetamide, potentially derived from the benzoxazinoid metabolites, were among the most discriminant postprandial plasma biomarkers distinguishing intake of breads containing whole-meal rye or rye bran from the control white wheat bread. Furthermore, subsequent metabolite profiling analysis of the consumed breads indicated that different bioprocessing/baking techniques involving exposure to microbial metabolism (e.g., sourdough fermentation) have a central role in modulating the phytochemical content of the whole-grain and bran-rich breads. PMID:24812068

  16. Bayesian derivation of plasma equilibrium distribution function for tokamak scenarios and the associated Landau collision operator

    NASA Astrophysics Data System (ADS)

    Di Troia, C.

    2015-11-01

    A class of parametric distribution functions was proposed in (Di Troia 2012 Plasma Phys. Control. Fusion 54 105017) as equilibrium distribution functions (EDFs) for charged particles in fusion plasmas, representing supra-thermal particles in anisotropic equilibria for Neutral Beam Injection and Ion Cyclotron Heating scenarios. Moreover, those EDFs can be used to represent also nearly isotropic equilibria for Slowing-Down alpha particles and core thermal plasma populations. Such EDFs depend on constants of motion (COMs). In axisymmetric system with no equilibrium electric field, they depend on toroidal canonical momentum {{P}φ} , kinetic energy w and magnetic moment μ. In the present work, the same EDFs are obtained from first principles and general hypothesis. The derivation is probabilistic and makes use of the Bayes’ Theorem. The bayesian argument is used to describe how the plasma is far from the prior probability distribution function (pdf), e.g. Maxwellian, based on the information obtained from magnetic moment and guiding center velocity pdf. Once the general functional form of the EDF has been settled, it is shown how to associate a modified Landau collision operator in the Fokker-Planck equation, to describe the system relaxation towards the proposed EDF.

  17. Detection of cellular prion protein in exosomes derived from ovine plasma.

    PubMed

    Berrone, Elena; Corona, Cristiano; Mazza, Maria; Vallino Costassa, Elena; Faro, Monica Lo; Properzi, Francesca; Guglielmetti, Chiara; Maurella, Cristiana; Caramelli, Maria; Deregibus, Maria Chiara; Camussi, Giovanni; Casalone, Cristina

    2015-12-01

    Prion protein (PrP) is present at extremely low levels in the blood of animals and its detection is complicated by the poor sensitivity of current standard methodologies. Interesting results have been obtained with recent advanced technologies that are able to detect minute amounts of the pathological PrP (PrPSc), but their efficiency is reduced by various factors present in blood. In this study, we were able to extract cellular PrP (PrPC) from plasma-derived exosomes by a simple, fast method without the use of differential ultracentrifugation and to visualize it by Western blotting, reducing the presence of most plasma proteins. This result confirms that blood is capable of releasing PrP in association with exosomes and could be useful to better study its role in the pathogenesis of transmissible spongiform encephalopathies. PMID:26399471

  18. Analytical characterization of plasma membrane-derived vesicles produced via osmotic and chemical vesiculation.

    PubMed

    Sarabipour, Sarvenaz; Chan, Robin B; Zhou, Bowen; Di Paolo, Gilbert; Hristova, Kalina

    2015-07-01

    Plasma membrane-derived vesicles are being used in biophysical and biochemical research as a simple, yet native-like model of the cellular membrane. Here we report on the characterization of vesicles produced via two different vesiculation methods from CHO and A431 cell lines. The first method is a recently developed method which utilizes chloride salts to induce osmotic vesiculation. The second is a well established chemical vesiculation method which uses DTT and formaldehyde. We show that both vesiculation methods produce vesicles which contain the lipid species previously reported in the plasma membrane of these cell lines. The two methods lead to small but statistically significant differences in two lipid species only; phosphatidylcholine (PC) and plasmalogen phosphatidylethanolamine (PEp). However, highly significant differences were observed in the degree of incorporation of a membrane receptor and in the degree of retention of soluble cytosolic proteins within the vesicles. PMID:25896659

  19. Safety assessment of azelaic acid and its derivatives entrapped in nanovesicles.

    PubMed

    Panyosak, A; Manosroi, J; Rojanasakul, Y; Manosroi, A

    2009-06-01

    The aim of this study was to determine the safety of azelaic acid (AA) and its derivatives in nanovesicles for pharmaceutical and cosmetic uses. The hydrophilic property of AA was modified by complexing AA with hydroxypropyl-beta-cyclodextrin (AACD). The lipophilic property of AA was improved to diethyl azelate (DA) by esterification with Fischer reaction. AA, AACD and DA were entrapped in liposomes and niosomes with the compositions of L-alpha-dipalmitoyl phosphatidylcholine/cholesterol = 7:3 and Tween 61/cholesterol = 1:1, respectively, by chloroform film method with sonication. The size of the vesicles ranged from 50 to 200 nm, indicating nanosize characteristics. The cytotoxicity of AA, AACD and DA entrapped nanovesicular formulations on mouse epidermal cell lines (JB6, normal cell lines) by the sulforhodamine B assay was modest when compared with cisplatin. Blank liposomes and niosomes gave no growth inhibitory effect. The irritation of AA, AACD and DA entrapped and not entrapped in nanovesicles on rabbit skin was examined according to the Environmental Protection Agency health effect test guidelines. The results showed no signs of erythema or edema within 72 h. AA and its derivatives were safe for topical use when entrapped in nanovesicles because of no toxicity to normal cell lines and no allergy on rabbit skin. PMID:19755450

  20. Diet-derived phenols in plasma and tissues and their implications for health.

    PubMed

    Clifford, M N

    2004-12-01

    This paper seeks to catalyse a reappraisal of the nature, fate and biological significance in humans of phenols, polyphenols and tannins (PPT) consumed in normal diets, and in particular questions the primacy of PPT radical-scavenging mechanisms for the supposed health benefits of diets rich in fruits and vegetables. PPT are classified by structure and function. Arguments are presented to show that cinnamates and derived polyphenols make significantly larger contributions to the total PPT intake than the flavonols and flavones upon which the vast majority of attention has been focussed previously. Daily intakes of total PPT may range from less than 100 mg to in excess of 2 g, and the critical importance of coffee and black tea as the major dietary sources is shown. Only some 5% of the dietary PPT is absorbed in the duodenum, and of this only some 5%, mainly flavanols, reaches the plasma unchanged, the balance being mammalian conjugates. Over 95% of the intake passes to the colon and is fermented by the gut microflora. A fraction of the resulting microbial metabolites is absorbed and appears in the plasma primarily as mammalian conjugates. Even following high intakes of PPT, the plasma metabolites collectively make a very small (less than 5%) and transient contribution to the total concentration of redox active substances in plasma. This explains the failure of most studies that sought to detect an increase in plasma antioxidant power after consuming a PPT-rich meal or supplement. The powerfully antioxidant PPT aglycones, much used in in vitro studies, do not reach the plasma. The redox potential of those unchanged PPT and PPT metabolites that reach the plasma enables them to scavenge damaging radicals, but the endogenous plasma antioxidants, especially ascorbate, are required for disposal of the resultant phenoxyl radicals. Black tea and coffee, the major sources of PPT, are poor sources of ascorbate. It is suggested that if diets rich in fruits and vegetables are

  1. Derivations and Comparisons of Three Groups ofSelf-Organization Theories for Magnetohydrodynamic Plasmas

    NASA Astrophysics Data System (ADS)

    Kondoh, Yoshiomi; Sato, Tetsuya

    1994-04-01

    A theoretical investigation on self-organization theories ofdissipative MHD plasmas is presented to derive three groups oftheories that lead to the same relaxed state of ∇ × B=λ B, in order to find more essential physicalpicture embedded in self-organization phenomena due to nonlinear anddissipative processes. Comparisons among all of the theories treatedand derived here suggest that a theory standing upon spectrumspreadings and selective dissipations of eigenmodes for thedissipative operator -∇ ×η j and leading toself-organized relaxed states of ∇ ×ηj=α B/2 with the minimum dissipation rate is the most agreeable to various results obtained by experiments and by 3-D MHD simulations reported so far.

  2. Pre-Clinical Study of a Novel Recombinant Botulinum Neurotoxin Derivative Engineered for Improved Safety

    PubMed Central

    Vazquez-Cintron, Edwin; Tenezaca, Luis; Angeles, Christopher; Syngkon, Aurelia; Liublinska, Victoria; Ichtchenko, Konstantin; Band, Philip

    2016-01-01

    Cyto-012 is a recombinant derivative of Botulinum neurotoxin Type A (BoNT/A). It primarily differs from wild type (wt) BoNT/A1 in that it incorporates two amino acid substitutions in the catalytic domain of the light chain (LC) metalloprotease (E224 > A and Y366 > A), designed to provide a safer clinical profile. Cyto-012 is specifically internalized into rat cortical and hippocampal neurons, and cleaves Synaptosomal-Associated Protein 25 (SNAP-25), the substrate of wt BoNT/A, but exhibits slower cleavage kinetics and therefore requires a higher absolute dose to exhibit pharmacologic activity. The pharmacodynamics of Cyto-012 and wt BoNT/A have similar onset and duration of action using the Digital Abduction Assay (DAS). Intramuscular LD50 values for Cyto-012 and wt BoNT/A respectively, were 0.63 ug (95% CI = 0.61, 0.66) and 6.22 pg (95% CI = 5.42, 7.02). ED50 values for Cyto-012 and wt BoNT/A were respectively, 0.030 ug (95% CI = 0.026, 0.034) and 0.592 pg (95% CI = 0.488, 0.696). The safety margin (intramuscular LD50/ED50 ratio) for Cyto-012 was found to be improved 2-fold relative to wt BoNT/A (p < 0.001). The DAS response to Cyto-012 was diminished when a second injection was administered 32 days after the first. These data suggest that the safety margin of BoNT/A can be improved by modulating their activity towards SNAP-25. PMID:27484492

  3. Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products.

    PubMed

    Fruijtier-Pölloth, Claudia

    2005-10-15

    This assessment focusses on polyethylene glycols (PEGs) and on anionic or nonionic PEG derivatives, which are currently used in cosmetics in Europe. These compounds are used in a great variety of cosmetic applications because of their solubility and viscosity properties, and because of their low toxicity. The PEGs, their ethers, and their fatty acid esters produce little or no ocular or dermal irritation and have extremely low acute and chronic toxicities. They do not readily penetrate intact skin, and in view of the wide use of preparations containing PEG and PEG derivatives, only few case reports on sensitisation reactions have been published, mainly involving patients with exposure to PEGs in medicines or following exposure to injured or chronically inflamed skin. On healthy skin, the sensitising potential of these compounds appears to be negligible. For some representative substances of this class, information was available on reproductive and developmental toxicity, on genotoxicty and carcinogenic properties. Taking into consideration all available information from related compounds, as well as the mode and mechanism of action, no safety concern with regard to these endpoints could be identified. Based on the available data it is therefore concluded that PEGs of a wide molecular weight range (200 to over 10,000), their ethers (laureths. ceteths, ceteareths, steareths, and oleths), and fatty acid esters (laurates, dilaurates, stearates, distearates) are safe for use in cosmetics. Limited data were available for PEG sorbitan/sorbitol fatty acid esters, PEG sorbitan beeswax and PEG soy sterols. Taking into account all the information available for closely related compounds, it can be assumed that these compounds as presently used in cosmetic preparations will not present a risk for human health. PEG castor oils and PEG hydrogenated castor oils have caused anaphylactic reactions when used in intravenous medicinal products. Their topical use in cosmetics is

  4. Controlling Microbial Safety Challenges of Meat Using High Voltage Atmospheric Cold Plasma.

    PubMed

    Han, Lu; Ziuzina, Dana; Heslin, Caitlin; Boehm, Daniela; Patange, Apurva; Sango, David M; Valdramidis, Vasilis P; Cullen, Patrick J; Bourke, Paula

    2016-01-01

    Atmospheric cold plasma (ACP) is a non-thermal technology, effective against a wide range of pathogenic microorganisms. Inactivation efficacy results from plasma generated reactive species. These may interact with any organic components in a test matrix including the target microorganism, thus food components may exert a protective effect against the antimicrobial mode of action. The effect of an in-package high voltage ACP process applied in conjunction with common meat processing MAP gas compositions as well as bacteria type and meat model media composition have been investigated to determine the applicability of this technology for decontamination of safety challenges associated with meat products. E. coli, L. monocytogenes, and S. aureus in PBS were undetectable after 60 s of treatment at 80 kVRMS in air, while ACP treatment of the contaminated meat model required post-treatment refrigeration to retain antimicrobial effect. The nutritive components in the meat model exerted a protective effect during treatment, where 300 s ACP exposure yielded a maximum reduction of 1.5 log using a high oxygen atmosphere, whilst using air and high nitrogen atmospheres yielded lower antimicrobial efficacy. Furthermore, an ROS assay was performed to understand the protective effects observed using the meat model. This revealed that nutritive components inhibited penetration of ROS into bacterial cells. This knowledge can assist the optimization of meat decontamination using ACP technology where interactions with all components of the food matrix require evaluation. PMID:27446018

  5. Controlling Microbial Safety Challenges of Meat Using High Voltage Atmospheric Cold Plasma

    PubMed Central

    Han, Lu; Ziuzina, Dana; Heslin, Caitlin; Boehm, Daniela; Patange, Apurva; Sango, David M.; Valdramidis, Vasilis P.; Cullen, Patrick J.; Bourke, Paula

    2016-01-01

    Atmospheric cold plasma (ACP) is a non-thermal technology, effective against a wide range of pathogenic microorganisms. Inactivation efficacy results from plasma generated reactive species. These may interact with any organic components in a test matrix including the target microorganism, thus food components may exert a protective effect against the antimicrobial mode of action. The effect of an in-package high voltage ACP process applied in conjunction with common meat processing MAP gas compositions as well as bacteria type and meat model media composition have been investigated to determine the applicability of this technology for decontamination of safety challenges associated with meat products. E. coli, L. monocytogenes, and S. aureus in PBS were undetectable after 60 s of treatment at 80 kVRMS in air, while ACP treatment of the contaminated meat model required post-treatment refrigeration to retain antimicrobial effect. The nutritive components in the meat model exerted a protective effect during treatment, where 300 s ACP exposure yielded a maximum reduction of 1.5 log using a high oxygen atmosphere, whilst using air and high nitrogen atmospheres yielded lower antimicrobial efficacy. Furthermore, an ROS assay was performed to understand the protective effects observed using the meat model. This revealed that nutritive components inhibited penetration of ROS into bacterial cells. This knowledge can assist the optimization of meat decontamination using ACP technology where interactions with all components of the food matrix require evaluation. PMID:27446018

  6. The significance of fibrinogen derivatives in plasma in human renal failure.

    PubMed

    Lane, D A; Ireland, H; Knight, I; Wolff, S; Kyle, P; Curtis, J R

    1984-02-01

    The concentrations in plasma of fibrinogen derivatives fibrinopeptide A (FPA), beta 15-42 antigen and fragment E (FgE) antigen have been determined in patients with renal failure and compared to the concentrations of the platelet release products, beta-thromboglobulin (beta TG) and platelet factor 4 (PF4). In 'partial renal failure' (51Cr-EDTA clearance rate 4-60 ml/min) FPA, beta 15-42 antigen, FgE antigen and beta TG levels were significantly raised above a normal laboratory control group. These levels were further raised in a group of patients whose disease required regular maintenance haemodialysis (51Cr-EDTA clearance rate less than 4 ml/min). PF4 levels were not significantly raised in either group. A statistical analysis of all patient results revealed that FPA, beta 15-42 antigen and FgE antigen levels all correlated with beta TG levels but not with PF4 levels. It is known that beta TG is catabolized by the kidney but PF4 is not and that elevated beta TG levels in renal failure are caused by impaired elimination rather than increased production. These results suggest that the plasma levels of these three fibrinogen derivatives are elevated in renal disease at least in part by decreased elimination rather than by increased thrombin and plasmin activities alone. PMID:6229269

  7. Triazene drug metabolites. Part 17: Synthesis and plasma hydrolysis of acyloxymethyl carbamate derivatives of antitumour triazenes.

    PubMed

    Carvalho, E; Francisco, A P; Iley, J; Rosa, E

    2000-07-01

    A series of 3-acyloxymethyloxycarbonyl-1-aryl-3-methyltriazenes 5 was synthesised by the sequential reaction of 1-aryl-3-methyltriazenes with (i) chloromethyl chloroformate, (ii) NaI in dry acetone, and (iii) either the silver carboxylate or the carboxylic acids in the presence of silver carbonate. The hydrolysis of these compounds was studied in pH 7.7 isotonic phosphate buffer and in human plasma. Triazene acyloxycarbamates demonstrated their ability to act as substrates for plasma enzymes. For compound 5f, a pH-rate profile was obtained which showed the hydrolysis to involve acid-base catalysis. The reaction is also buffer catalysed. Thus, at pH 7.7, pH-independent, base-catalysed and buffer-catalysed processes all contribute to the hydrolysis reaction. The sensitivity of the hydrolysis reaction to various structural parameters in the substrates indicates that hydrolysis occurs at the ester rather than the carbamate functionality. In plasma, the rates of hydrolysis correlate with partition coefficients, the most lipophilic compounds being the most stable. An aspirin derivative suffers two consecutive enzymatic reactions, the scission of the aspirin acetyl group being followed by the scission of the acyloxy ester group. These results indicate that triazene acyloxymethyl carbamates are prodrugs of the antitumour monomethyltriazenes. They combine chemical stability with a rapid enzymatic hydrolysis, and are consequently good candidates for further prodrug development. Moreover, this type of derivative allowed the synthesis of mutual prodrugs, associating the antitumour monomethyltriazenes with anti-inflammatory NSAIDs as well as with the anticancer agent butyric acid. PMID:10976519

  8. Impact of Protein Stability, Cellular Localization, and Abundance on Proteomic Detection of Tumor-Derived Proteins in Plasma

    PubMed Central

    Faca, Vitor M.; Zhang, Wenxuan; Zhang, Qing; Jain, Anjali; Hanash, Sam; Agus, David B.; McIntosh, Martin W.; Mallick, Parag

    2011-01-01

    Tumor-derived, circulating proteins are potentially useful as biomarkers for detection of cancer, for monitoring of disease progression, regression and recurrence, and for assessment of therapeutic response. Here we interrogated how a protein's stability, cellular localization, and abundance affect its observability in blood by mass-spectrometry-based proteomics techniques. We performed proteomic profiling on tumors and plasma from two different xenograft mouse models. A statistical analysis of this data revealed protein properties indicative of the detection level in plasma. Though 20% of the proteins identified in plasma were tumor-derived, only 5% of the proteins observed in the tumor tissue were found in plasma. Both intracellular and extracellular tumor proteins were observed in plasma; however, after normalizing for tumor abundance, extracellular proteins were seven times more likely to be detected. Although proteins that were more abundant in the tumor were also more likely to be observed in plasma, the relationship was nonlinear: Doubling the spectral count increased detection rate by only 50%. Many secreted proteins, even those with relatively low spectral count, were observed in plasma, but few low abundance intracellular proteins were observed. Proteins predicted to be stable by dipeptide composition were significantly more likely to be identified in plasma than less stable proteins. The number of tryptic peptides in a protein was not significantly related to the chance of a protein being observed in plasma. Quantitative comparison of large versus small tumors revealed that the abundance of proteins in plasma as measured by spectral count was associated with the tumor size, but the relationship was not one-to-one; a 3-fold decrease in tumor size resulted in a 16-fold decrease in protein abundance in plasma. This study provides quantitative support for a tumor-derived marker prioritization strategy that favors secreted and stable proteins over all but the

  9. Impact of protein stability, cellular localization, and abundance on proteomic detection of tumor-derived proteins in plasma.

    PubMed

    Fang, Qiaojun; Kani, Kian; Faca, Vitor M; Zhang, Wenxuan; Zhang, Qing; Jain, Anjali; Hanash, Sam; Agus, David B; McIntosh, Martin W; Mallick, Parag

    2011-01-01

    Tumor-derived, circulating proteins are potentially useful as biomarkers for detection of cancer, for monitoring of disease progression, regression and recurrence, and for assessment of therapeutic response. Here we interrogated how a protein's stability, cellular localization, and abundance affect its observability in blood by mass-spectrometry-based proteomics techniques. We performed proteomic profiling on tumors and plasma from two different xenograft mouse models. A statistical analysis of this data revealed protein properties indicative of the detection level in plasma. Though 20% of the proteins identified in plasma were tumor-derived, only 5% of the proteins observed in the tumor tissue were found in plasma. Both intracellular and extracellular tumor proteins were observed in plasma; however, after normalizing for tumor abundance, extracellular proteins were seven times more likely to be detected. Although proteins that were more abundant in the tumor were also more likely to be observed in plasma, the relationship was nonlinear: Doubling the spectral count increased detection rate by only 50%. Many secreted proteins, even those with relatively low spectral count, were observed in plasma, but few low abundance intracellular proteins were observed. Proteins predicted to be stable by dipeptide composition were significantly more likely to be identified in plasma than less stable proteins. The number of tryptic peptides in a protein was not significantly related to the chance of a protein being observed in plasma. Quantitative comparison of large versus small tumors revealed that the abundance of proteins in plasma as measured by spectral count was associated with the tumor size, but the relationship was not one-to-one; a 3-fold decrease in tumor size resulted in a 16-fold decrease in protein abundance in plasma. This study provides quantitative support for a tumor-derived marker prioritization strategy that favors secreted and stable proteins over all but the

  10. Final Report: Safety of Plasma Components and Aerosol Transport During Hard Disruptions and Accidental Energy Release in Fusion Reactor

    SciTech Connect

    Bourham, Mohamed A.; Gilligan, John G.

    1999-08-14

    Safety considerations in large future fusion reactors like ITER are important before licensing the reactor. Several scenarios are considered hazardous, which include safety of plasma-facing components during hard disruptions, high heat fluxes and thermal stresses during normal operation, accidental energy release, and aerosol formation and transport. Disruption events, in large tokamaks like ITER, are expected to produce local heat fluxes on plasma-facing components, which may exceed 100 GW/m{sup 2} over a period of about 0.1 ms. As a result, the surface temperature dramatically increases, which results in surface melting and vaporization, and produces thermal stresses and surface erosion. Plasma-facing components safety issues extends to cover a wide range of possible scenarios, including disruption severity and the impact of plasma-facing components on disruption parameters, accidental energy release and short/long term LOCA's, and formation of airborne particles by convective current transport during a LOVA (water/air ingress disruption) accident scenario. Study, and evaluation of, disruption-induced aerosol generation and mobilization is essential to characterize database on particulate formation and distribution for large future fusion tokamak reactor like ITER. In order to provide database relevant to ITER, the SIRENS electrothermal plasma facility at NCSU has been modified to closely simulate heat fluxes expected in ITER.

  11. Chemical compositional, biological, and safety studies of a novel maple syrup derived extract for nutraceutical applications.

    PubMed

    Zhang, Yan; Yuan, Tao; Li, Liya; Nahar, Pragati; Slitt, Angela; Seeram, Navindra P

    2014-07-16

    Maple syrup has nutraceutical potential given the macronutrients (carbohydrates, primarily sucrose), micronutrients (minerals and vitamins), and phytochemicals (primarily phenolics) found in this natural sweetener. We conducted compositional (ash, fiber, carbohydrates, minerals, amino acids, organic acids, vitamins, phytochemicals), in vitro biological, and in vivo safety (animal toxicity) studies on maple syrup extracts (MSX-1 and MSX-2) derived from two declassified maple syrup samples. Along with macronutrient and micronutrient quantification, thirty-three phytochemicals were identified (by HPLC-DAD), and nine phytochemicals, including two new compounds, were isolated and identified (by NMR) from MSX. At doses of up to 1000 mg/kg/day, MSX was well tolerated with no signs of overt toxicity in rats. MSX showed antioxidant (2,2-diphenyl-1-picrylhydrazyl (DPPH) assay) and anti-inflammatory (in RAW 264.7 macrophages) effects and inhibited glucose consumption (by HepG2 cells) in vitro. Thus, MSX should be further investigated for potential nutraceutical applications given its similarity in chemical composition to pure maple syrup. PMID:24983789

  12. Chemical Compositional, Biological, and Safety Studies of a Novel Maple Syrup Derived Extract for Nutraceutical Applications

    PubMed Central

    2015-01-01

    Maple syrup has nutraceutical potential given the macronutrients (carbohydrates, primarily sucrose), micronutrients (minerals and vitamins), and phytochemicals (primarily phenolics) found in this natural sweetener. We conducted compositional (ash, fiber, carbohydrates, minerals, amino acids, organic acids, vitamins, phytochemicals), in vitro biological, and in vivo safety (animal toxicity) studies on maple syrup extracts (MSX-1 and MSX-2) derived from two declassified maple syrup samples. Along with macronutrient and micronutrient quantification, thirty-three phytochemicals were identified (by HPLC-DAD), and nine phytochemicals, including two new compounds, were isolated and identified (by NMR) from MSX. At doses of up to 1000 mg/kg/day, MSX was well tolerated with no signs of overt toxicity in rats. MSX showed antioxidant (2,2-diphenyl-1-picrylhydrazyl (DPPH) assay) and anti-inflammatory (in RAW 264.7 macrophages) effects and inhibited glucose consumption (by HepG2 cells) in vitro. Thus, MSX should be further investigated for potential nutraceutical applications given its similarity in chemical composition to pure maple syrup. PMID:24983789

  13. Plasma gasification of refuse derived fuel in a single-stage system using different gasifying agents.

    PubMed

    Agon, N; Hrabovský, M; Chumak, O; Hlína, M; Kopecký, V; Masláni, A; Bosmans, A; Helsen, L; Skoblja, S; Van Oost, G; Vierendeels, J

    2016-01-01

    The renewable evolution in the energy industry and the depletion of natural resources are putting pressure on the waste industry to shift towards flexible treatment technologies with efficient materials and/or energy recovery. In this context, a thermochemical conversion method of recent interest is plasma gasification, which is capable of producing syngas from a wide variety of waste streams. The produced syngas can be valorized for both energetic (heat and/or electricity) and chemical (ammonia, hydrogen or liquid hydrocarbons) end-purposes. This paper evaluates the performance of experiments on a single-stage plasma gasification system for the treatment of refuse-derived fuel (RDF) from excavated waste. A comparative analysis of the syngas characteristics and process yields was done for seven cases with different types of gasifying agents (CO2+O2, H2O, CO2+H2O and O2+H2O). The syngas compositions were compared to the thermodynamic equilibrium compositions and the performance of the single-stage plasma gasification of RDF was compared to that of similar experiments with biomass and to the performance of a two-stage plasma gasification process with RDF. The temperature range of the experiment was from 1400 to 1600 K and for all cases, a medium calorific value syngas was produced with lower heating values up to 10.9 MJ/Nm(3), low levels of tar, high levels of CO and H2 and which composition was in good agreement to the equilibrium composition. The carbon conversion efficiency ranged from 80% to 100% and maximum cold gas efficiency and mechanical gasification efficiency of respectively 56% and 95%, were registered. Overall, the treatment of RDF proved to be less performant than that of biomass in the same system. Compared to a two-stage plasma gasification system, the produced syngas from the single-stage reactor showed more favourable characteristics, while the recovery of the solid residue as a vitrified slag is an advantage of the two-stage set-up. PMID:26210232

  14. Safety and Efficacy of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Therapy for Retinal Degeneration

    PubMed Central

    Leow, S. N.; Luu, Chi D.; Hairul Nizam, M. H.; Mok, P. L.; Ruhaslizan, R.; Wong, H. S.; Wan Abdul Halim, Wan Haslina; Ng, M. H.; Ruszymah, B. H. I.; Chowdhury, S. R.; Bastion, M. L. C.; Then, K. Y.

    2015-01-01

    Purpose To investigate the safety and efficacy of subretinal injection of human Wharton’s Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats. Methods RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies. Results No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells. Conclusions Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies. PMID:26107378

  15. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection.

    PubMed

    Sódar, Barbara W; Kittel, Ágnes; Pálóczi, Krisztina; Vukman, Krisztina V; Osteikoetxea, Xabier; Szabó-Taylor, Katalin; Németh, Andrea; Sperlágh, Beáta; Baranyai, Tamás; Giricz, Zoltán; Wiener, Zoltán; Turiák, Lilla; Drahos, László; Pállinger, Éva; Vékey, Károly; Ferdinandy, Péter; Falus, András; Buzás, Edit Irén

    2016-01-01

    Circulating extracellular vesicles have emerged as potential new biomarkers in a wide variety of diseases. Despite the increasing interest, their isolation and purification from body fluids remains challenging. Here we studied human pre-prandial and 4 hours postprandial platelet-free blood plasma samples as well as human platelet concentrates. Using flow cytometry, we found that the majority of circulating particles within the size range of extracellular vesicles lacked common vesicular markers. We identified most of these particles as lipoproteins (predominantly low-density lipoprotein, LDL) which mimicked the characteristics of extracellular vesicles and also co-purified with them. Based on biophysical properties of LDL this finding was highly unexpected. Current state-of-the-art extracellular vesicle isolation and purification methods did not result in lipoprotein-free vesicle preparations from blood plasma or from platelet concentrates. Furthermore, transmission electron microscopy showed an association of LDL with isolated vesicles upon in vitro mixing. This is the first study to show co-purification and in vitro association of LDL with extracellular vesicles and its interference with vesicle analysis. Our data point to the importance of careful study design and data interpretation in studies using blood-derived extracellular vesicles with special focus on potentially co-purified LDL. PMID:27087061

  16. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection

    PubMed Central

    Sódar, Barbara W; Kittel, Ágnes; Pálóczi, Krisztina; Vukman, Krisztina V; Osteikoetxea, Xabier; Szabó-Taylor, Katalin; Németh, Andrea; Sperlágh, Beáta; Baranyai, Tamás; Giricz, Zoltán; Wiener, Zoltán; Turiák, Lilla; Drahos, László; Pállinger, Éva; Vékey, Károly; Ferdinandy, Péter; Falus, András; Buzás, Edit Irén

    2016-01-01

    Circulating extracellular vesicles have emerged as potential new biomarkers in a wide variety of diseases. Despite the increasing interest, their isolation and purification from body fluids remains challenging. Here we studied human pre-prandial and 4 hours postprandial platelet-free blood plasma samples as well as human platelet concentrates. Using flow cytometry, we found that the majority of circulating particles within the size range of extracellular vesicles lacked common vesicular markers. We identified most of these particles as lipoproteins (predominantly low-density lipoprotein, LDL) which mimicked the characteristics of extracellular vesicles and also co-purified with them. Based on biophysical properties of LDL this finding was highly unexpected. Current state-of-the-art extracellular vesicle isolation and purification methods did not result in lipoprotein-free vesicle preparations from blood plasma or from platelet concentrates. Furthermore, transmission electron microscopy showed an association of LDL with isolated vesicles upon in vitro mixing. This is the first study to show co-purification and in vitro association of LDL with extracellular vesicles and its interference with vesicle analysis. Our data point to the importance of careful study design and data interpretation in studies using blood-derived extracellular vesicles with special focus on potentially co-purified LDL. PMID:27087061

  17. Characterization of plasma treated surfaces for food safety by terahertz spectroscopy

    NASA Astrophysics Data System (ADS)

    Sulovská, Kateřina; Lehocký, Marián.

    2014-10-01

    A physico-chemical approach to modify surfaces not only for use in medicine, but also for preservation of food is nowadays widely studied to lower the risks of increased number of bacterial pathogens that are in a direct contact with people. Food safety is very important part of preserving sustainability during crises, especially after the enterohaemorrhagic Escherichia coli outbreak in Europe in 2011. One of the possibility how we can protect food against various pathogens is the modification of packing materials that are directly in contact with preserved food. This contribution deals with the characterization of modified surfaces with antibacterial properties via Terahertz spectroscopy. For the purpose of this paper, three monomers were used for grafting onto air radiofrequency plasma activated low density polyethylene surface, which created a brush-like structure. Next, the antibacterial agents, Irgasan and Chlorhexidine, were anchored to these surfaces. These antibacterial agents were selected for supposed effect on two most frequently occurring bacterial strains - Escherichia coli and Staphylococcus aureus. Materials were further tested for the presence of antibacterial agent molecules, in our case by means of terahertz spectroscopy. Each material was tested on two spectroscopes - the SPECTRA and the OSCAT terahertz instruments.

  18. Equation of state of the one-component plasma derived from precision Monte Carlo calculations

    SciTech Connect

    Stringfellow, G.S. Institute of Geophysics and Planetary Physics Lawrence Livermore National Laboratory, Livermore, California 94550 ); DeWitt, H.E. ); Slattery, W.L. )

    1990-01-15

    Analytical fits to the one-component plasma (OCP) equation of state have been derived for internal energies that have reduced all {ital N}-dependent effects to within the statistical uncertainties introduced by the Monte Carlo computational process, which themselves are very small. Values of {ital N}{approx gt}500 adequately represent the thermodynamic limit. Using the fluid internal energies for only {ital N}=686, various analytical fits are generated, compared, and discussed. The thermal energy is accurately represented by a simple power-series fit with the leading term given by {Gamma}{sup 1/3}, but also requires a small correction to the bcc Madelung term that brings that coefficient down to nearly {minus}0.9, the value derived for hypernetted-chain theory. The fluid thermal energy data are reproduced to better than 0.2% over all {Gamma} by our fit(s). The solid phase requires {ital both} anharmonic terms to be included in the fit, implying that the previous justification for dropping the first anharmonic correction is unwarranted. The location of the fluid-solid phase transition utilizing these new fits yields {Gamma}{sub bcc}=178 and {Gamma}{sub fcc}=192.

  19. Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy

    PubMed Central

    Ahn, James; Ahn, Hyung Seok; Cheong, Jae Hoon; dela Peña, Ike

    2016-01-01

    Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD. The analysis indicated mixed findings with regard to efficacy of natural product-derived ADHD interventions. Nevertheless, these treatments were considered as a “safer” approach than conventional ADHD medications. More comprehensive and appropriately controlled clinical studies are required to fully ascertain efficacy and safety of natural product-derived ADHD treatments. Studies that replicate encouraging findings on the efficacy of combining botanical agents and nutritional supplements with other natural product-derived therapies and widely used ADHD medications are also warranted. In conclusion, the risk-benefit balance of natural product-derived ADHD treatments should be carefully monitored when used as standalone treatment or when combined with other conventional ADHD treatments. PMID:26966583

  20. Innovative Plasma Disinfection Technique with the Reduced-pH Method and the Plasma-Treated Water (PTW) -Safety and Powerful Disinfection with Cryopreserved PTW-

    NASA Astrophysics Data System (ADS)

    Kitano, Katsuhisa; Ikawa, Satoshi; Nakashima, Yoichi; Tani, Atsushi; Yokoyama, Takashi; Ohshima, Tomoko

    2015-09-01

    Among the applications of the plasma disinfection to human body, plasma sterilization in liquid is crucial. We found that the plasma-treated water (PTW) has strong bactericidal activity under low pH condition and the half-lives of its activity depend on temperature. Lower temperature brings longer half-life and the bactericidal activity of PTW can be kept by cryopreservation. These physicochemical properties were in accordance with Arrhenius equation both in liquid and solid states. From the experimental results of ESR (Electron Spin Resonance) measurement of O2-in liquid against PTW with spin trapping method, half-lives of PTW were also in accordance with Arrhenius equation. It suggests that high concentration PTW as integrated value can be achieved by cooling of plasma apparatus. Pure PTW has disinfection power of 22 log reduction (B. subtilis). This corresponds to 65% H2O2, 14% hypochlorous acid and 0.33% peracetic acid, which are deadly poison for human. On the other hand, PTW is deactivated soon at body temperature. This indicates that toxicity to human body seems to be low. PTW, which is a sort of indirect plasma exposure, with pH and temperature controls could be applied for safety and powerful disinfection. MEXT (15H03583, 23340176, 25108505). NCCE (23-A-15).

  1. Safety.

    ERIC Educational Resources Information Center

    Education in Science, 1996

    1996-01-01

    Discusses safety issues in science, including: allergic reactions to peanuts used in experiments; explosions in lead/acid batteries; and inspection of pressure vessels, such as pressure cookers or model steam engines. (MKR)

  2. Plasma binding proteins for platelet-derived growth factor that inhibit its binding to cell-surface receptors.

    PubMed Central

    Raines, E W; Bowen-Pope, D F; Ross, R

    1984-01-01

    Evidence is presented that the binding of platelet-derived growth factor (PDGF) to plasma constituents inhibits the binding of PDGF to its cell-surface mitogen receptor. Approximately equivalent amounts of PDGF-binding activity were found in plasma from a number of different species known by radioreceptor assay to contain PDGF homologues in their clotted blood. Activation of the coagulation cascade did not significantly alter the PDGF-binding activity of the plasma components. Three molecular weight classes of plasma fractions that inhibit PDGF binding to its cell-surface receptor were defined by gel filtration: approximately equal to 40,000, 150,000, and greater than 500,000. Specific binding of 125I-labeled PDGF to the highest molecular weight plasma fraction could also be demonstrated by gel filtration. The binding of PDGF to these plasma components was reversible under conditions of low pH or with guanidine X HCl, and active PDGF could be recovered from the higher molecular weight fractions. Immunologic and functional evidence is presented that the highest molecular weight plasma fraction may be alpha 2-macroglobulin. A model is proposed in which the activity of PDGF released in vivo may be regulated by association with these plasma binding components and by high-affinity binding to cell-surface PDGF receptors. PMID:6203121

  3. Plasma brain-derived neurotrophic factor levels are increased in patients with tinnitus and correlated with therapeutic effects.

    PubMed

    Xiong, Hao; Yang, Haidi; Liang, Maojin; Ou, Yongkang; Huang, Xiayin; Cai, Yuexin; Lai, Lan; Pang, Jiaqi; Zheng, Yiqing

    2016-05-27

    Tinnitus is the perception of sound without an external source and is known to be associated with altered neuronal excitability in the auditory system. Tinnitus severity can be assessed by various psychometric instruments and there is no objective measures developed to evaluate tinnitus severity and therapeutic effects so far. Brain-derived nerve growth factor (BDNF) is believed in playing a key role in regulating neuronal excitability in the brain. To determine whether BDNF correlates with tinnitus induction and severity, we described plasma BDNF levels in patients with tinnitus and healthy controls and evaluated the correlation between plasma BDNF levels and tinnitus severity measured by Tinnitus Handicap Inventory (THI) and Visual Analog Scale (VAS). Moreover, alteration of plasma BDNF levels before and after tinnitus retraining therapy (TRT) in patients with severe tinnitus was also analyzed. We found plasma BDNF levels were elevated in patients with tinnitus compared with healthy controls. In addition, plasma BDNF levels in patients with severe tinnitus were decreased significantly after effective TRT. However, plasma BDNF levels were not correlated with tinnitus loudness and tinnitus severity measured by THI and VAS. These findings support plasma BDNF as a marker for activity changes in the auditory system and could possibly evaluate therapeutic effects in patients with tinnitus. PMID:27095590

  4. Amino Acid Derivatives as Palmitoylethanolamide Prodrugs: Synthesis, In Vitro Metabolism and In Vivo Plasma Profile in Rats

    PubMed Central

    Vacondio, Federica; Bassi, Michele; Silva, Claudia; Castelli, Riccardo; Carmi, Caterina; Scalvini, Laura; Lodola, Alessio; Vivo, Valentina; Flammini, Lisa; Barocelli, Elisabetta; Mor, Marco; Rivara, Silvia

    2015-01-01

    Palmitoylethanolamide (PEA) has antinflammatory and antinociceptive properties widely exploited in veterinary and human medicine, despite its poor pharmacokinetics. Looking for prodrugs that could progressively release PEA to maintain effective plasma concentrations, we prepared carbonates, esters and carbamates at the hydroxyl group of PEA. Chemical stability (pH 7.4) and stability in rat plasma and liver homogenate were evaluated by in vitro assays. Carbonates and carbamates resulted too labile and too resistant in plasma, respectively. Ester derivatives, prepared by conjugating PEA with various amino acids, allowed to modulate the kinetics of PEA release in plasma and stability in liver homogenate. L-Val-PEA, with suitable PEA release in plasma, and D-Val-PEA, with high resistance to hepatic degradation, were orally administered to rats and plasma levels of prodrugs and PEA were measured at different time points. Both prodrugs showed significant release of PEA, but provided lower plasma concentrations than those obtained with equimolar doses of PEA. Amino-acid esters of PEA are a promising class to develop prodrugs, even if they need further chemical optimization. PMID:26053855

  5. Hepatitis E virus derived from different sources exhibits different behaviour in virus inactivation and/or removal studies with plasma derivatives.

    PubMed

    Yunoki, Mikihiro; Tanaka, Hiroyuki; Takahashi, Kadue; Urayama, Takeru; Hattori, Shinji; Ideno, Shoji; Furuki, Rie; Sakai, Kaoru; Hagiwara, Katsuro; Ikuta, Kazuyoshi

    2016-09-01

    Hepatitis E virus (HEV) causes viral hepatitis, and is considered a risk factor for blood products. Although some HEV inactivation/removal studies have been reported, detailed investigations of different manufacturing steps as heat treatment, partitioning during cold ethanol fractionation, low pH treatment, and virus filtration have yet to be reported for plasma-derived medicinal products. In this study, human serum- and swine faeces-derived HEVs, with and without detergent treatment, were used. The kinetic patterns of inactivation, log reduction value, or partitioning during the process were evaluated. In addition, the mouse encephalomyocarditis virus (EMCV) and canine and porcine parvoviruses (CPV/PPV) were also evaluated as model viruses for HEV. Small pore size (19 or 15 nm) virus filtration demonstrated effective removal of HEV. Middle pore size (35 nm) virus filtration and 60 °C liquid heating demonstrated moderate inactivation/removal. Ethanol fractionation steps demonstrated limited removal of HEV. Unpurified HEV exhibited different properties than the detergent-treated HEV, and both forms displayed differences when compared with EMCV, CPV, and PPV. Limited or no inactivation of HEV was observed during low pH treatment. Untreated plasma-derived HEV from humans showed different properties compared to that of HEV treated with detergent or derived from swine faeces. Therefore, HEV spike preparation requires more attention. PMID:27461242

  6. Pharmacokinetics and safety of resveratrol derivatives in humans after oral administration of melinjo (Gnetum gnemon L.) seed extract powder.

    PubMed

    Tani, Hiroko; Hikami, Susumu; Iizuna, Sanae; Yoshimatsu, Maiko; Asama, Takashi; Ota, Hidetaka; Kimura, Yuka; Tatefuji, Tomoki; Hashimoto, Ken; Higaki, Kazutaka

    2014-02-26

    Fruits and seeds of melinjo (Gnetum gnemon L.) are resveratrol derivative-rich materials. Pharmacokinetics of resveratrol derivatives in healthy volunteers after oral administration of 1000 mg of melinjo seed extract (MSE) powder were assessed and compared with those after oral dosing of trans-resveratrol (tRV) powder containing 4.8 mg of tRV only, equivalent to the content in 1000 mg MSE powder. Plasma tRV concentrations with enzymatic hydrolysis were maintained over 24 h, with a tmax of 12 h and a mean residence time (MRT) of 14 h, 5 and 2 times higher than those for tRV powder intake, respectively. Gnetin C, a resveratrol dimer, with hydrolysis was maintained in plasma for >96 h with a 36 h MRT. With repeated doses once daily for 28 days, plasma tRV and gnetin C concentrations with hydrolysis were in good agreement with the theoretical curves. MSE powder was well tolerated up to the oral dosing of 5000 mg with no serious adverse events. PMID:24495149

  7. Modest Attenuation of HIV-1 Vpu Alleles Derived from Elite Controller Plasma

    PubMed Central

    Chen, Jingyan; Tibroni, Nadine; Sauter, Daniel; Galaski, Johanna; Miura, Toshiyuki; Alter, Galit; Mueller, Birthe; Haller, Claudia; Walker, Bruce D.; Kirchhoff, Frank; Brumme, Zabrina L.; Ueno, Takamasa; Fackler, Oliver T.

    2015-01-01

    In the absence of antiretroviral therapy, infection with human immunodeficiency virus type 1 (HIV-1) can typically not be controlled by the infected host and results in the development of acquired immunodeficiency. In rare cases, however, patients spontaneously control HIV-1 replication. Mechanisms by which such elite controllers (ECs) achieve control of HIV-1 replication include particularly efficient immune responses as well as reduced fitness of the specific virus strains. To address whether polymorphisms in the accessory HIV-1 protein Vpu are associated with EC status we functionally analyzed a panel of plasma-derived vpu alleles from 15 EC and 16 chronic progressor (CP) patients. Antagonism of the HIV particle release restriction by the intrinsic immunity factor CD317/tetherin was well conserved among EC and CP Vpu alleles, underscoring the selective advantage of this Vpu function in HIV-1 infected individuals. In contrast, interference with CD317/tetherin induced NF-κB activation was little conserved in both groups. EC Vpus more frequently displayed reduced ability to downregulate cell surface levels of CD4 and MHC class I (MHC-I) molecules as well as of the NK cell ligand NTB-A. Polymorphisms potentially associated with high affinity interactions of the inhibitory killer immunoglobulin-like receptor (KIR) KIR2DL2 were significantly enriched among EC Vpus but did not account for these functional differences. Together these results suggest that in a subgroup of EC patients, some Vpu functions are modestly reduced, possibly as a result of host selection. PMID:25793728

  8. Multifunctional Transmembrane Protein Ligands for Cell-Specific Targeting of Plasma Membrane-Derived Vesicles.

    PubMed

    Zhao, Chi; Busch, David J; Vershel, Connor P; Stachowiak, Jeanne C

    2016-07-01

    Liposomes and nanoparticles that bind selectively to cell-surface receptors can target specific populations of cells. However, chemical conjugation of ligands to these particles is difficult to control, frequently limiting ligand uniformity and complexity. In contrast, the surfaces of living cells are decorated with highly uniform populations of sophisticated transmembrane proteins. Toward harnessing cellular capabilities, here it is demonstrated that plasma membrane vesicles (PMVs) derived from donor cells can display engineered transmembrane protein ligands that precisely target cells on the basis of receptor expression. These multifunctional targeting proteins incorporate (i) a protein ligand, (ii) an intrinsically disordered protein spacer to make the ligand sterically accessible, and (iii) a fluorescent protein domain that enables quantification of the ligand density on the PMV surface. PMVs that display targeting proteins with affinity for the epidermal growth factor receptor (EGFR) bind at increasing concentrations to breast cancer cells that express increasing levels of EGFR. Further, as an example of the generality of this approach, PMVs expressing a single-domain antibody against green fluorescence protein (eGFP) bind to cells expressing eGFP-tagged receptors with a selectivity of ≈50:1. The results demonstrate the versatility of PMVs as cell targeting systems, suggesting diverse applications from drug delivery to tissue engineering. PMID:27294846

  9. Stem Cells and Stem Cell-derived Tissues and Their Use in Safety Assessment*

    PubMed Central

    Kolaja, Kyle

    2014-01-01

    Toxicology has long relied on animal models in a tedious approach to understanding risk of exposure to an uncharacterized molecule. Stem cell-derived tissues can be made in high purity, quality, and quantity to enable a new approach to this problem. Currently, stem cell-derived tissues are primarily “generic” genetic backgrounds; the future will see the integration of various genetic backgrounds and complex three-dimensional models to create truly unique in vitro organoids. This minireview focuses on the state of the art of a number of stem cell-derived tissues and details their application in toxicology. PMID:24362027

  10. Elevated Plasma Stromal-Cell-Derived Factor-1 Protein Levels Correlate with Severity in Patients with Community-Acquired Pneumonia

    PubMed Central

    Tsai, Ping-Kun; Hsieh, Ming-Ju; Wang, Hsiang-Ling; Chou, Ming-Chih; Yang, Shun-Fa

    2014-01-01

    Background. The aim of this study was to investigate differential changes in plasma levels of stromal-cell-derived factor-1 (SDF-1) before and after antibiotic treatment in patients with community-acquired pneumonia (CAP) and observe the association between the severity of CAP and the plasma SDF-1 level. Methods. We gathered blood specimens from 61 adult CAP patients before and after antibiotic treatment and from 60 healthy controls to measure the plasma concentrations of SDF-1 by using an enzyme-linked immunosorbent assay. Results. The plasma SDF-1 concentration was elevated significantly in patients with CAP before receiving treatment compared with the controls and decreased significantly after the patients received treatment. Leukocyte (WBC) and neutrophil counts and C-reactive protein (CRP) levels decreased significantly after antibiotic treatment. Moreover, differences in the plasma concentration of SDF-1 were significantly correlated with PSI, CURB-65, and APACHE II scores (r = 0.389, P = 0.002, and n = 61; r = 0.449, P < 0.001, and n = 61; and r = 0.363, P = 0.004, and n = 61, resp.). Conclusions. An elevated plasma SDF-1 concentration can be used as a biological marker for the early diagnosis of CAP and for the early detection of its severity. PMID:25371597

  11. Pharmacokinetics and safety of a novel recombinant human von Willebrand factor manufactured with a plasma-free method: a prospective clinical trial

    PubMed Central

    Mannucci, Pier Mannuccio; Kempton, Christine; Millar, Carolyn; Romond, Edward; Shapiro, Amy; Birschmann, Ingvild; Ragni, Margaret V.; Gill, Joan Cox; Yee, Thynn Thynn; Klamroth, Robert; Wong, Wing-Yen; Chapman, Miranda; Engl, Werner; Turecek, Peter L.; Suiter, Tobias M.

    2013-01-01

    Safety and pharmacokinetics (PK) of recombinant von Willebrand factor (rVWF) combined at a fixed ratio with recombinant factor VIII (rFVIII) were investigated in 32 subjects with type 3 or severe type 1 von Willebrand disease (VWD) in a prospective phase 1, multicenter, randomized clinical trial. rVWF was well tolerated and no thrombotic events, inhibitors, or serious adverse events were observed. The PK of rVWF ristocetin cofactor activity, VWF antigen, and collagen-binding activity were similar to those of the comparator plasma-derived (pd) VWF-pdFVIII. In vivo cleavage of ultra-large molecular-weight rVWF multimers by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; the endogenous VWF protease) and generation of characteristic satellite bands were demonstrated. In 2 subjects with specific nonneutralizing anti-VWF–binding antibodies already detectable before rVWF infusion, a reduction in VWF multimers and VWF activity was observed. Stabilization of endogenous FVIII was enhanced following post–rVWF-rFVIII infusion as shown by the difference in area under the plasma concentration curve compared with pdVWF-pdFVIII (AUC0-∞) (P < .01). These data support the concept of administering rVWF alone once a therapeutic level of endogenous FVIII is achieved. This trial was registered at www.clinicaltrials.gov as #NCT00816660. PMID:23777763

  12. The safety assessment of food ingredients derived from plant cell, tissue and organ cultures: a review.

    PubMed

    Murthy, Hosakatte Niranjana; Georgiev, Milen I; Park, So-Young; Dandin, Vijayalaxmi S; Paek, Kee-Yoeup

    2015-06-01

    Plant cell, tissue and organ cultures (PCTOC) have become an increasingly attractive alternative for the production of various high molecular weight molecules which are used as flavourings, fragrances, colouring agents and food additives. Although PCTOC products are cultivated in vitro in a contamination free environment, the raw material produced from PCTOC may contain many components apart from the target compound. In some cases, PCTOC raw materials may also carry toxins, which may be naturally occurring or accumulated during the culture process. Assessment of the safety of PCTOC products is, therefore, a priority of the biotech industries involved in their production. The safety assessment involves the evaluation of starting material, production process and the end product. Before commercialisation, PCTOC products should be evaluated for their chemical and biological properties, as well as for their toxicity. In this review, measures and general criteria for biosafety evaluation of PCTOC products are addressed and thoroughly discussed. PMID:25624252

  13. Characterization of equatorial plasma depletions detected from derived GPS data in South America

    NASA Astrophysics Data System (ADS)

    Magdaleno, S.; Herraiz, M.; de La Morena, B. A.

    2012-01-01

    The equatorial plasma bubbles (EPBs) have been studied using slant total electron content (sTEC) derived from GPS data. The sTEC has been calculated from data measured at 15 International GNSS Service (IGS) stations located from 90°W to 30°W, covering the ionospheric equatorial anomaly at the American sector, for the years 2000, 2001, 2004, 2005 and 2008. The Ionospheric Bubbles Seeker (IBS) application has been used to detect and characterize the sTEC depletions associated to the EPBs. This technique bases its analysis on the time-variation of the sTEC and the population variance of this time-variation. The default configuration has been used and an EPB has been considered when a sTEC depletion was greater than 5 TEC units (TECu). The hourly occurrence shows the well-known maximum number of depletions after the post-sunset. The monthly occurrence of the EPBs is also analyzed and compared with previous studies. The International Reference Ionosphere model (IRI) has been used to calculate the equatorial vertical drift (EVD) and the peak densities of the E- and F-layers (NmE and NmF2, respectively). The EVD variation has been compared with the seasonal variation of the EPB. A discussion between the yearly mean occurrence EPBs rate and the solar activity is included. The variation of the yearly mean depth and duration of the sTEC depletions with the solar activity conditions and its relation with the ionospheric characteristics given by the IRI model has been also studied.

  14. Effects of meteor head plasma distribution on radar cross sections and derived meteoroid masses

    NASA Astrophysics Data System (ADS)

    Marshall, R. A.; Close, S.; Brown, P.; Dimant, Y.

    2016-01-01

    We present calculations that relate meteor head echo radar cross sections to the meteor head plasma distribution. We use a forward model of radar scattering from meteor plasma using a finite-difference time-domain (FDTD) model of the electromagnetic wave interaction with the plasma. This model computes the meteor head RCS for a given meteor plasma distribution, specified with a peak plasma density and a characteristic size. We then relate measured RCS values to the input size and density parameters to better characterize the meteor plasma. We present simulation results that show that the RCS is directly related to the overdense meteor area; that is, the cross-section area of the meteor inside which the plasma frequency exceeds the radar frequency. This provides a direct estimate of the meteor plasma size from a given RCS measurement. Next we investigate the effect of the assumed plasma distribution. We study the RCS resulting from Gaussian, parabolic exponential and 1/r2 distributions. Comparing the different calculated RCS from these different distributions to three-frequency head echo data from the CMOR radar, we show that the 1/r2 distribution provides the best fit to the data. However, given uncertainties in the data, we cannot conclude that any distribution is the most valid. In addition, we show that the choice of distribution assumed can alter the resulting line density q by an order of magnitude for the same data.

  15. The safety of herbal medicinal products derived from Echinacea species: a systematic review.

    PubMed

    Huntley, Alyson L; Thompson Coon, Joanna; Ernst, Edzard

    2005-01-01

    Echinacea spp. are native to North America and were traditionally used by the Indian tribes for a variety of ailments, including mouth sores, colds and snake-bites. The three most commonly used Echinacea spp. are E. angustifolia, E. pallida and E. purpurea. Systematic literature searches were conducted in six electronic databases and the reference lists of all of the papers located were checked for further relevant publications. Information was also sought from the spontaneous reporting programmes of the WHO and national drug safety bodies. Twenty-three manufacturers of echinacea were contacted and asked for data held on file. Finally our own departmental files were searched. No language restrictions were imposed. Combination products and homeopathic preparations were excluded. Data from clinical studies and spontaneous reporting programmes suggest that adverse events with echinacea are not commonly reported. Gastrointestinal upsets and rashes occur most frequently. However, in rare cases, echinacea can be associated with allergic reactions that may be severe. Although there is a large amount of data that investigates the efficacy of echinacea, safety issues and the monitoring of adverse events have not been focused on. Short-term use of echinacea is associated with a relatively good safety profile, with a slight risk of transient, reversible, adverse events. The association of echinacea with allergic reactions is supported by the present evaluation. While these reactions are likely to be rare, patients with allergy or asthma should carefully consider their use of echinacea. The use of echinacea products during pregnancy and lactation would appear to be ill-advised in light of the paucity of data in this area. PMID:15853441

  16. The relevance of gene transfer to the safety of food and feed derived from genetically modified (GM) plants.

    PubMed

    van den Eede, G; Aarts, H; Buhk, H-J; Corthier, G; Flint, H J; Hammes, W; Jacobsen, B; Midtvedt, T; van der Vossen, J; von Wright, A; Wackernagel, W; Wilcks, A

    2004-07-01

    In 2000, the thematic network ENTRANSFOOD was launched to assess four different topics that are all related to the testing or assessment of food containing or produced from genetically modified organisms (GMOs). Each of the topics was linked to a European Commission (EC)-funded large shared cost action (see http://www.entransfood.com). Since the exchange of genetic information through horizontal (lateral) gene transfer (HGT) might play a more important role, in quantity and quality, than hitherto imagined, a working group dealing with HGT in the context of food and feed safety was established. This working group was linked to the GMOBILITY project (GMOBILITY, 2003) and the results of the deliberations are laid down in this review paper. HGT is reviewed in relation to the potential risks of consuming food or feed derived from transgenic crops. First, the mechanisms for obtaining transgenic crops are described. Next, HGT mechanisms and its possible evolutionary role are described. The use of marker genes is presented in detail as a special case for genes that may pose a risk. Furthermore, the exposure to GMOs and in particular to genetically modified (GM) deoxyribonucleic acid (DNA) is discussed as part of the total risk assessment. The review finishes off with a number of conclusions related to GM food and feed safety. The aim of this paper is to provide a comprehensive overview to assist risk assessors as well as regulators and the general public in understanding the safety issues related to these mechanisms. PMID:15123384

  17. First assessment in humans of the safety, tolerability, pharmacokinetics, and ex vivo pharmacodynamic antimalarial activity of the new artemisinin derivative artemisone.

    PubMed

    Nagelschmitz, Johannes; Voith, Barbara; Wensing, Georg; Roemer, Axel; Fugmann, Burkhard; Haynes, Richard K; Kotecka, Barbara M; Rieckmann, Karl H; Edstein, Michael D

    2008-09-01

    In preclinical studies, artemisone (BAY 44-9585), a new artemisinin derivative, was shown to possess enhanced efficacy over artesunate, and it does not possess the neurotoxicity characteristic of the current artemisinins. In a phase I program with double-blind, randomized, placebo-controlled, single and multiple ascending oral-dose studies, we evaluated the safety, tolerability, pharmacokinetics, and ex vivo pharmacodynamic antimalarial activity of artemisone. Single doses (10, 20, 30, 40, and 80 mg) and multiple doses (40 and 80 mg daily for 3 days) of artemisone were administered orally to healthy subjects. Plasma concentrations of artemisone and its metabolites were measured by liquid chromatography/tandem mass spectrometry (LC/MS-MS). Artemisone was well tolerated, with no serious adverse events and no clinically relevant changes in laboratory and vital parameters. The pharmacokinetics of artemisone over the 10- to 80-mg range demonstrated dose linearity. After the single 80-mg dose, artemisone had a geometric mean maximum concentration of 140.2 ng/ml (range, 86.6 to 391.0), a short elimination half-life (t(1/2)) of 2.79 h (range, 1.56 to 4.88), a high oral clearance of 284.1 liters/h (range, 106.7 to 546.7), and a large volume of distribution of 14.50 liters/kg (range, 3.21 to 51.58). Due to artemisone's short t(1/2), its pharmacokinetics were comparable after single and multiple dosing. Plasma samples taken after multiple dosing showed marked ex vivo pharmacodynamic antimalarial activities against two multidrug-resistant Plasmodium falciparum lines. Artemisone equivalent concentrations measured by bioassay revealed higher activity than artemisone measured by LC/MS-MS, confirming the presence of active metabolites. Comparable to those of other artemisinin's, artemisone's t(1/2) is well suited for artemisinin-based combination therapy for the treatment of P. falciparum malaria. PMID:18559649

  18. First Assessment in Humans of the Safety, Tolerability, Pharmacokinetics, and Ex Vivo Pharmacodynamic Antimalarial Activity of the New Artemisinin Derivative Artemisone▿

    PubMed Central

    Nagelschmitz, Johannes; Voith, Barbara; Wensing, Georg; Roemer, Axel; Fugmann, Burkhard; Haynes, Richard K.; Kotecka, Barbara M.; Rieckmann, Karl H.; Edstein, Michael D.

    2008-01-01

    In preclinical studies, artemisone (BAY 44-9585), a new artemisinin derivative, was shown to possess enhanced efficacy over artesunate, and it does not possess the neurotoxicity characteristic of the current artemisinins. In a phase I program with double-blind, randomized, placebo-controlled, single and multiple ascending oral-dose studies, we evaluated the safety, tolerability, pharmacokinetics, and ex vivo pharmacodynamic antimalarial activity of artemisone. Single doses (10, 20, 30, 40, and 80 mg) and multiple doses (40 and 80 mg daily for 3 days) of artemisone were administered orally to healthy subjects. Plasma concentrations of artemisone and its metabolites were measured by liquid chromatography/tandem mass spectrometry (LC/MS-MS). Artemisone was well tolerated, with no serious adverse events and no clinically relevant changes in laboratory and vital parameters. The pharmacokinetics of artemisone over the 10- to 80-mg range demonstrated dose linearity. After the single 80-mg dose, artemisone had a geometric mean maximum concentration of 140.2 ng/ml (range, 86.6 to 391.0), a short elimination half-life (t1/2) of 2.79 h (range, 1.56 to 4.88), a high oral clearance of 284.1 liters/h (range, 106.7 to 546.7), and a large volume of distribution of 14.50 liters/kg (range, 3.21 to 51.58). Due to artemisone's short t1/2, its pharmacokinetics were comparable after single and multiple dosing. Plasma samples taken after multiple dosing showed marked ex vivo pharmacodynamic antimalarial activities against two multidrug-resistant Plasmodium falciparum lines. Artemisone equivalent concentrations measured by bioassay revealed higher activity than artemisone measured by LC/MS-MS, confirming the presence of active metabolites. Comparable to those of other artemisinin's, artemisone's t1/2 is well suited for artemisinin-based combination therapy for the treatment of P. falciparum malaria. PMID:18559649

  19. Safety and nutritional assessment of GM plants and derived food and feed: the role of animal feeding trials.

    PubMed

    2008-03-01

    In this report the various elements of the safety and nutritional assessment procedure for genetically modified (GM) plant derived food and feed are discussed, in particular the potential and limitations of animal feeding trials for the safety and nutritional testing of whole GM food and feed. The general principles for the risk assessment of GM plants and derived food and feed are followed, as described in the EFSA guidance document of the EFSA Scientific Panel on Genetically Modified Organisms. In Section 1 the mandate, scope and general principles for risk assessment of GM plant derived food and feed are discussed. Products under consideration are food and feed derived from GM plants, such as maize, soybeans, oilseed rape and cotton, modified through the introduction of one or more genes coding for agronomic input traits like herbicide tolerance and/or insect resistance. Furthermore GM plant derived food and feed, which have been obtained through extensive genetic modifications targeted at specific alterations of metabolic pathways leading to improved nutritional and/or health characteristics, such as rice containing beta-carotene, soybeans with enhanced oleic acid content, or tomato with increased concentration of flavonoids, are considered. The safety assessment of GM plants and derived food and feed follows a comparative approach, i.e. the food and feed are compared with their non-GM counterparts in order to identify intended and unintended (unexpected) differences which subsequently are assessed with respect to their potential impact on the environment, safety for humans and animals, and nutritional quality. Key elements of the assessment procedure are the molecular, compositional, phenotypic and agronomic analysis in order to identify similarities and differences between the GM plant and its near isogenic counterpart. The safety assessment is focussed on (i) the presence and characteristics of newly expressed proteins and other new constituents and possible

  20. Nutritional value and safety of methionine derivatives, isomeric dipeptides and hydroxy analogs in mice.

    PubMed

    Friedman, M; Gumbmann, M R

    1988-03-01

    Weight gains in mice fed amino acid diets containing methionine and 16 methionine derivatives and analogs were compared at graded dietary concentrations. Linear response was closely approximated for concentrations below those yielding maximum growth. Derivatization of L-methionine generally lowered potency, calculated as the ratio of the slopes of the two dose-response curves. However, the three isomeric dipeptides L-L-, L-D- and D-L-methionylmethionine, N-acetyl- and N-formyl-L-methionine, L-methionine sulfoxide and D-methionine were well utilized. The double derivative N-acetyl-L-methionine sulfoxide reduced potency below 60%. D-Methionine sulfoxide, N-acetyl-D-methionine and D-methionyl-D-methionine had potencies between 4 and 40%. The calcium salts of L- and D-alpha-hydroxy analogs of methionine had potencies of 55.4 and 85.7%, respectively. Several of the analogs were less growth-inhibiting or toxic at high concentrations in the diet than was L-methionine. These results imply that some methionine dipeptides or analogs may be better candidates for fortifying foods than L-methionine. Possible biochemical pathways for the utilization of methionine derivatives and analogs are also described. PMID:3351635

  1. Human Adipose-Derived Mesenchymal Stem Cells in Cell Therapy: Safety and Feasibility in Different "Hospital Exemption" Clinical Applications

    PubMed Central

    Vériter, Sophie; André, Wivine; Aouassar, Najima; Poirel, Hélène Antoine; Lafosse, Aurore; Docquier, Pierre-Louis; Dufrane, Denis

    2015-01-01

    Based on immunomodulatory, osteogenic, and pro-angiogenic properties of adipose-derived stem cells (ASCs), this study aims to assess the safety and efficacy of ASC-derived cell therapies for clinical indications. Two autologous ASC-derived products were proposed to 17 patients who had not experienced any success with conventional therapies: (1) a scaffold-free osteogenic three-dimensional graft for the treatment of bone non-union and (2) a biological dressing for dermal reconstruction of non-healing chronic wounds. Safety was studied using the quality control of the final product (genetic stability, microbiological/mycoplasma/endotoxin contamination) and the in vivo evaluation of adverse events after transplantation. Feasibility was assessed by the ability to reproducibly obtain the final ASC-based product with specific characteristics, the time necessary for graft manufacturing, the capacity to produce enough material to treat the lesion, the surgical handling of the graft, and the ability to manufacture the graft in line with hospital exemption regulations. For 16 patients (one patient did not undergo grafting because of spontaneous bone healing), in-process controls found no microbiological/mycoplasma/endotoxin contamination, no obvious deleterious genomic anomalies, and optimal ASC purity. Each type of graft was reproducibly obtained without significant delay for implantation and surgical handling was always according to the surgical procedure and the implantation site. No serious adverse events were noted for up to 54 months. We demonstrated that autologous ASC transplantation can be considered a safe and feasible therapy tool for extreme clinical indications of ASC properties and physiopathology of disease. PMID:26485394

  2. Colon-derived uremic biomarkers induced by the acute toxicity of Kansui radix: A metabolomics study of rat plasma and intestinal contents by UPLC-QTOF-MS(E).

    PubMed

    Yang, Zhou; Hou, Jin-Jun; Qi, Peng; Yang, Min; Yan, Bing-Peng; Bi, Qi-Rui; Feng, Rui-Hong; Yang, Wen-Zhi; Wu, Wan-Ying; Guo, De-An

    2016-07-15

    Kansui radix (KR) is a poisonous Chinese herbal medicine recorded in the Chinese Pharmacopoeia, and the acute toxicity obstructs its clinical applications. To explore its acute toxicity mechanism to enhance clinical safety, a metabolomics study based on UPLC-ESI-QTOF-MS(E) was performed. Wistar rats were exposed for 4h to the aqueous and ethyl acetate extracts prepared from KR at a high dose (25g/kg). The contents of six different sections of rat intestine, including the duodenum, jejunum, ileum, cecum, colon, and rectum were collected as samples for the first time, as well as the rat plasma. The interesting results showed that only those rats exposed to the ethyl acetate extract showed a watery diarrhea, similar to the observed acute human toxicity. The identified biomarkers found in the plasma, such as phenol sulfate, indoxyl sulfate, and p-cresol sulfate were significantly perturbed in the rats. These biomarkers are known as colon-derived uremic compounds, which were first reported with respect to KR. The three essential amino acids which produced these biomarkers were only found in the contents of colon and rectum. A hypothesis was proposed that only the colon-derived uremic compounds induced by KR might be responsible for the acute toxicity. Three traditional process methods to reduce the toxicity of KR were compared based on these biomarkers, and different levels of toxicity modulation were observed. These results may be helpful to further understand the mechanism of acute toxicity, and the relevance of the traditional process methods to ameliorate the adverse effects of KR. PMID:26433353

  3. Quality standards, safety and efficacy of blood-derived serum eye drops: A review.

    PubMed

    van der Meer, Pieter F; Seghatchian, Jerard; Marks, Denese C

    2016-02-01

    Serum eye drops (SEDs) are being used increasingly to treat dry eye syndrome and persistent corneal epithelial defects, and are usually prescribed when conventional treatments fail. SEDs are commonly sourced from the patient's own blood via an autologous collection. Although SEDs are clearly beneficial, they are not available for those patients that cannot donate sufficient blood, and some centres are moving to allogeneic SEDs. Many studies have reported that both allogeneic and autologous SEDs are effective. However, few large randomised controlled trials have been conducted to date, and clinical evidence is therefore limited to smaller studies. Alternatives to serum are also being explored, such as platelet lysate and products made from platelet rich plasma, as they are a rich source of growth factors. This article reviews how some centres are approaching allogeneic collections for SEDs, and alternatives to serum that are currently being explored. PMID:26847866

  4. Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability.

    PubMed

    Kinney, William A; McDonnell, Mark E; Zhong, Hua Marlon; Liu, Chaomin; Yang, Lanyi; Ling, Wei; Qian, Tao; Chen, Yu; Cai, Zhijie; Petkanas, Dean; Brenneman, Douglas E

    2016-04-14

    Cannabidiol is the nonpsychoactive natural component of C. sativa that has been shown to be neuroprotective in multiple animal models. Our interest is to advance a therapeutic candidate for the orphan indication hepatic encephalopathy (HE). HE is a serious neurological disorder that occurs in patients with cirrhosis or liver failure. Although cannabidiol is effective in models of HE, it has limitations in terms of safety and oral bioavailability. Herein, we describe a series of side chain modified resorcinols that were designed for greater hydrophilicity and "drug likeness", while varying hydrogen bond donors, acceptors, architecture, basicity, neutrality, acidity, and polar surface area within the pendent group. Our primary screen evaluated the ability of the test agents to prevent damage to hippocampal neurons induced by ammonium acetate and ethanol at clinically relevant concentrations. Notably, KLS-13019 was 50-fold more potent and >400-fold safer than cannabidiol and exhibited an in vitro profile consistent with improved oral bioavailability. PMID:27096053

  5. Food safety concerns deriving from the use of silver based food packaging materials

    PubMed Central

    Pezzuto, Alessandra; Losasso, Carmen; Mancin, Marzia; Gallocchio, Federica; Piovesana, Alessia; Binato, Giovanni; Gallina, Albino; Marangon, Alberto; Mioni, Renzo; Favretti, Michela; Ricci, Antonia

    2015-01-01

    The formulation of innovative packaging solutions, exerting a functional antimicrobial role in slowing down food spoilage, is expected to have a significant impact on the food industry, allowing both the maintenance of food safety criteria for longer periods and the reduction of food waste. Different materials are considered able to exert the required antimicrobial activity, among which are materials containing silver. However, challenges exist in the application of silver to food contact materials due to knowledge gaps in the production of ingredients, stability of delivery systems in food matrices and health risks caused by the same properties which also offer the benefits. Aims of the present study were to test the effectiveness and suitability of two packaging systems, one of which contained silver, for packaging and storing Stracchino cheese, a typical Italian fresh cheese, and to investigate if there was any potential for consumers to be exposed to silver, via migration from the packaging to the cheese. Results did not show any significant difference in the effectiveness of the packaging systems on packaged Stracchino cheese, excluding that the active packaging systems exerted an inhibitory effect on the growth of spoilage microorganisms. Moreover, silver migrated into the cheese matrix throughout the storage time (24 days). Silver levels in cheese finally exceeded the maximum established level for the migration of a non-authorised substance through a functional barrier (Commission of the European Communities, 2009). This result poses safety concerns and strongly suggests the need for more research aimed at better characterizing the new packaging materials in terms of their potential impacts on human health and the environment. PMID:26500642

  6. Intestinal Microbiota-Derived Metabolomic Blood Plasma Markers for Prior Radiation Injury

    SciTech Connect

    Ó Broin, Pilib; Vaitheesvaran, Bhavapriya; Saha, Subhrajit; Hartil, Kirsten; Chen, Emily I.; Goldman, Devorah; Fleming, William Harv; Kurland, Irwin J.; Guha, Chandan; Golden, Aaron

    2015-02-01

    Purpose: Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Methods and Materials: Groups of C57BL/6 mice (n=12 per group) were exposed to 0, 2, 4, 8, and 10.4 Gy of whole-body gamma radiation. At 24 hours after treatment, all animals were euthanized, and both plasma and liver biopsy samples were obtained, the latter being used to identify a distinct hepatic radiation injury response within plasma. A semiquantitative, untargeted metabolite/lipid profile was developed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, which identified 354 biochemical compounds. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. Results: We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Conclusions: Plasma profiling of specific metabolites related to pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan-associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites particularly represent an attractive marker for radiation injury within blood plasma.

  7. Intestinal Microbiota Derived Metabolomic Blood Plasma Markers for Prior Radiation Injury

    PubMed Central

    Broin, Pilib Ó; Vaitheesvaran, Bhavapriya; Saha, Subhrajit; Hartil, Kirsten; Chen, Emily I.; Goldman, Devorah; Fleming, William Harv; Kurland, Irwin J.; Guha, Chandan; Golden, Aaron

    2014-01-01

    Purpose Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Methods and Materials Groups of C57BL/6 mice (n=12 per group) were exposed to 0 Gy, 2 Gy, 4 Gy, 8 Gy, and 10.4 Gy of whole-body γ-radiation. At 24 hours post treatment all animals were euthanized and both plasma and liver biopsies obtained - the latter being used to deconvolve a distinct hepatic radiation injury response within plasma. A semi-quantitative untargeted metabolites/lipid profiling using both GC/MS and LC/MS/MS platforms was performed and identified 354 biochemicals. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. Results We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence to indicate that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Conclusion Plasma profiling of specific metabolites related to the pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites in particular represent an attractive marker for radiation injury within blood plasma. PMID:25636760

  8. Cassava (Manihot esculenta Crantz) and Yam (Dioscorea spp.) Crops and Their Derived Foodstuffs: Safety, Security and Nutritional Value.

    PubMed

    Ferraro, Vincenza; Piccirillo, Clara; Tomlins, Keith; Pintado, Manuela E

    2016-12-01

    Cassava (Manihot esculenta Crantz) and yam (Dioscorea spp.) are tropical crops consumed by ca. 2 billion people and represent the main source of carbohydrate and energy for the approximately 700 million people living in the tropical and sub-tropical areas. They are a guarantee of food security for developing countries. The production of these crops and the transformation into food-derived commodities is increasing, it represents a profitable business and farmers generate substantial income from their market. However, there are some important concerns related to the food safety and food security. The high post-harvest losses, mainly for yam, the contamination by endogenous toxic compounds, mainly for cassava, and the contamination by external agents (such as micotoxins, pesticides, and heavy metal) represent a depletion of economic value and income. The loss in the raw crops or the impossibility to market the derived foodstuffs, due to incompliance with food regulations, can seriously limit all yam tubers and the cassava roots processors, from farmers to household, from small-medium to large enterprises. One of the greatest challenges to overcome those concerns is the transformation of traditional or indigenous processing methods into modern industrial operations, from the crop storage to the adequate package of each derived foodstuff. PMID:26165549

  9. International movement of plasma and plasma contracting.

    PubMed

    Farrugia, A

    2005-01-01

    Plasma fractionation is a global business characterised by technological stability, increasing consolidation and a high level of regulatory oversight. All these factors affect the ease with which plasma derivatives can be accessed in the world market. As domestic regulatory measures in the first world blood economies become increasingly resonant to the precautionary approach, the availability of plasma as a raw material, as well as its cost, become an increasingly significant component in the cost of the final product. This decreases the amount of plasma which fractionators are able to allocate for export activities. Also, regulatory standards in the country of manufacture will reflect priorities in that country which may not be similar to those in export markets, but which will affect entry to those markets. While many countries possess a fractionation capacity, the limiting factor in supply worldwide is the amount of plasma available, and nationalistic drivers for each country to have its own plant are inimical to product safety and supply. Rather, the provision of sufficient supplies of domestic plasma should be the focus of resource allocation, with a choice of an appropriate contract fractionator. However, contract fractionation too may be affected by domestic considerations unrelated to the needs of the country of plasma origin. This chapter will review the global plasma market and the influences on plasma and plasma product movement across national borders. Problems in ensuring adequate safety and supply will be identified, and some tentative approaches to the amelioration of current barriers to the provision of plasma derivatives will be outlined. PMID:16050160

  10. Methylglyoxal-derived hydroimidazolone residue of plasma protein can behave as a predictor of prediabetes in Spontaneously Diabetic Torii rats

    PubMed Central

    Chen, Si Jing; Aikawa, Chiwa; Yoshida, Risa; Matsui, Toshiro

    2015-01-01

    Prediabetes, typically defined as impaired glucose tolerance and/or impaired fasting blood glucose, is a high-risk state of developing diabetes. The association of diabetes-related metabolites with prediabetes has not been investigated intensively. This study aimed to get insights into the metabolic behaviors of some typical diabetes-related metabolites in plasma of male Spontaneously Diabetic Torii (SDT) rats during pathogenic progress of diabetes and to assess in vivo if the variation in these metabolites related to the progression of prediabetic stage. To address this question, SDT rats and Sprague Dawley (SD) rats as control were maintained from the age of 7 to 25 weeks. Five typical advanced glycation end products (AGEs) residue of plasma protein and their free adducts were determined by liquid chromatography with tandem mass detection over the duration of the investigation. The SDT rats exhibited impaired glucose tolerance since the age of 12 weeks and developed diabetes with significantly elevated fasting glucose levels after 22 weeks. At the prediabetic stage (12–21 weeks), no significant differences were observed on AGE-free adducts levels of SDT rats compared with SD rats. However, methylglyoxal-derived hydroimidazolone (MG-H1) residue contents of plasma protein were significantly elevated in SDT rats at the age of 16 weeks, whereas other AGE residues of plasma protein did not show marked difference. The present study has revealed significant increase in MG-H1 residue content of plasma protein at the prediabetic stage of a spontaneously diabetic rat model, irrespective of unaltered fasting blood glucose and constant plasma levels of other AGEs. PMID:26265747

  11. Clinical safety and tolerability issues in use of triazole derivatives in management of fungal infections

    PubMed Central

    Neofytos, Dionissios; Avdic, Edina; Magiorakos, Anna-Pelagia

    2010-01-01

    There has been an increase in the number of patients susceptible to invasive fungal infections (IFIs) leading to a greater need for effective, well tolerated, and easily administered antifungal agents. The advent of triazoles has revolutionized the care of patients requiring treatment or prophylaxis for IFIs. However, triazoles have been associated with a number of adverse events and significant drug–drug interactions. While commonly used, physicians and patients should be aware of the distinct properties of these agents in order to ensure that patients are optimally treated with the least amount of toxicity possible. Clinicians should have a full understanding of the basic pharmacokinetics, absorption, and bioavailability of triazoles. Moreover, knowledge of the drug–drug interactions and potential toxicities of each agent is critical prior to administering a triazole. Careful history taking, thorough review of the patient’s medication list, and detailed discussion with the patients and their families about the efficacy, safety, and tolerability of these agents should be performed. Clinicians treating patients with triazoles should closely follow them, monitor pertinent laboratory tests, and consider measuring drug levels as needed. This article will review the basic pharmacokinetic properties and most frequently encountered adverse events and pitfalls associated with triazoles in clinical practice. PMID:21701616

  12. The variant Creutzfeldt-Jakob Disease: Risk, uncertainty or safety in the use of blood and blood derivatives?

    PubMed

    Liras, Antonio

    2008-01-01

    It has been long since French physician Jean-Baptiste Denys carried out the first successful blood transfusion to a human being. Using bird feathers as canules, sheep blood was transfused to a young man. The patient died soon after Denys' treatment and Denys was accused of murder. In the XXI century, known as the biotechnology century, we face new challenges in Medicine. New emerging and reemerging diseases, such as Creutzfeldt-Jakob disease (CJD) or "mad cow disease" and its human variant (vCJD), challenge the biosafety aspects of a widely extended and extremely useful technique, that is, the perfusion of blood, of its derived components and of other pharmacological products obtained from plasma. To face these new challenges we need innovative prevention strategies. PMID:18573217

  13. A safety analysis of food waste-derived animal feeds from three typical conversion techniques in China.

    PubMed

    Chen, Ting; Jin, Yiying; Shen, Dongsheng

    2015-11-01

    This study was based on the food waste to animal feed demonstration projects in China. A safety analysis of animal feeds from three typical treatment processes (i.e., fermentation, heat treatment, and coupled hydrothermal treatment and fermentation) was presented. The following factors are considered in this study: nutritive values characterized by organoleptic properties and general nutritional indices; the presence of bovine- and sheep-derived materials; microbiological indices for Salmonella, total coliform (TC), total aerobic plate counts (TAC), molds and yeast (MY), Staphylococcus Aureus (SA), and Listeria; chemical contaminant indices for hazardous trace elements such as Cr, Cd, and As; and nitrite and organic contaminants such as aflatoxin B1 (AFB1) and hexachlorocyclohexane (HCH). The present study reveals that the feeds from all three conversion processes showed balanced nutritional content and retained a certain feed value. The microbiological indices and the chemical contaminant indices for HCH, dichlorodiphenyltrichloroethane (DDT), nitrite, and mercury all met pertinent feed standards; however, the presence of bovine- and sheep-derived materials and a few chemical contaminants such as Pb were close to or might exceed the legislation permitted values in animal feeding. From the view of treatment techniques, all feed retained part of the nutritional values of the food waste after the conversion processes. Controlled heat treatment can guarantee the inactivation of bacterial pathogens, but none of the three techniques can guarantee the absence of cattle- and sheep-derived materials and acceptable levels of certain contaminants. The results obtained in this research and the feedstuffs legislation related to animal feed indicated that food waste-derived feed could be considered an adequate alternative to be used in animal diets, while the feeding action should be changed with the different qualities of the products, such as restrictions on the application

  14. Safety evaluation of pectin-derived acidic oligosaccharides (pAOS): genotoxicity and sub-chronic studies.

    PubMed

    Garthoff, Jossie A; Heemskerk, Suzanne; Hempenius, Rixta A; Lina, Ben A R; Krul, Cyrille A M; Koeman, Jan H; Speijers, Gerrit J A

    2010-06-01

    Pectin-derived acidic oligosaccharides (pAOS) are non-digestible carbohydrates to be used in infant formulae and medical nutrition. To support its safety, the genotoxic potential of pAOS was evaluated. pAOS was not mutagenic in the Ames test. Positive results were obtained in the chromosome aberration test only at highly cytotoxic concentrations. The effects obtained in the mouse lymphoma test were equivocal; pAOS was not mutagenic in vivo. A sub-chronic dietary study, preceded by 4-week parental and in utero exposure phase, investigated general safety. Administration of pAOS did not affect parental health nor pup characteristics. No effects specific for acidic oligosaccharides were observed in the subsequent sub-chronic study. Slight diffuse hyperplasia of epithelial layer of the urinary bladder was noted to result from concurrently elevated urinary sodium, due to high sodium in pAOS, and elevated urinary pH. This phenomenon was confirmed in a mechanistic (sub-chronic) study. In contrast, in rats fed pAOS in combination with NH(4)Cl, an acidifying agent, the induced low urinary pH completely prevented the development of urothelial hyperplasia. Hyperplasia induced by this mechanism in rats is considered not relevant to man. Based on the current knowledge we consider pAOS safe for human consumption under its intended use. PMID:20026148

  15. The very-high-density lipoprotein fraction of rabbit plasma is rich in tissue-derived cholesterol.

    PubMed

    Nanjee, M N; Miller, N E

    1991-11-01

    When plasma from rabbits, which several weeks earlier had been infused with [3H]cholesterol, was subjected to equilibrium density gradient ultracentrifugation, the specific radioactivity of cholesterol in the very-high-density lipoprotein (VHDL) fraction (d 1.22-1.32 g/ml) was three to 8-fold greater (mean, 5.5-fold; P less than 0.001) than that in high-density lipoproteins (HDL; d 1.06-1.21 g/ml). On size exclusion chromatography of plasma, no increase in specific radioactivity was seen in particles smaller than HDL. These findings suggest that those apolipoprotein-lipid complexes that dissociate from HDL during ultracentrifugation to form the VHDL fraction contain proportionately more tissue-derived cholesterol than do those that are more tightly bound to HDL. PMID:1932106

  16. Plasma-derived exosomes in acute myeloid leukemia for detection of minimal residual disease: are we ready?

    PubMed

    Boyiadzis, Michael; Whiteside, Theresa L

    2016-06-01

    The recent emergence of plasma-derived exosomes as biomarkers of leukemic relapse has introduced the potential for more sensitive non-invasive monitoring of leukemia patients based on the molecular and genetic analysis of the exosome cargo. In principle, the protein, lipid, miRNA, mRNA or DNA profiles of exosomes in patients' plasma that associate with leukemic relapse can be identified. The diagnostic/prognostic value of these profiles could then be validated in prospective clinical studies. Here, we consider the potential of exosomes to fulfill the role of future biomarkers of minimal residual disease in AML. The rationale for developing exosome-based methodology for minimal residual disease detection is based on promising early observations. However, standards need to be established for evaluating exosome identity, isolation from body fluids, and assessment methods. The rapidly expanding knowledge of the exosome biology suggests that the exosome status as potential biomarkers may become clarified in the near future. PMID:27043038

  17. Food Safety and Intervention Technologies Research: Cold Plasma as a Nonthermal food processing technology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Contamination of meats, seafood, poultry, eggs, and fresh and fresh-cut fruits and vegetables is an ongoing concern. The Food Safety and Intervention Technologies Research Unit develops and validates innovative approaches and new technologies that control pathogenic bacteria and viruses while preser...

  18. Paracrine Diffusion of PrPC and Propagation of Prion Infectivity by Plasma Membrane-Derived Microvesicles

    PubMed Central

    Tasciotti, Vincenzo; Garofalo, Tina; Longo, Agostina; Boller, Klaus; Löwer, Johannes; Misasi, Roberta; Montrasio, Fabio; Sorice, Maurizio

    2009-01-01

    Cellular prion protein (PrPc) is a physiological constituent of eukaryotic cells. The cellular pathways underlying prions spread from the sites of prions infection/peripheral replication to the central nervous system are still not elucidated. Membrane-derived microvesicles (MVs) are submicron (0.1–1 µm) particles, that are released by cells during plasma membrane shedding processes. They are usually liberated from different cell types, mainly upon activation as well as apoptosis, in this case, one of their hallmarks is the exposure of phosphatidylserine in the outer leaflet of the membrane. MVs are also characterized by the presence of adhesion molecules, MHC I molecules, as well as of membrane antigens typical of their cell of origin. Evidence exists that MVs shedding provide vehicles to transfer molecules among cells, and that MVs are important modulators of cell-to-cell communication. In this study we therefore analyzed the potential role of membrane-derived MVs in the mechanism(s) of PrPC diffusion and prion infectivity transmission. We first identified PrPC in association with the lipid raft components Fyn, flotillin-2, GM1 and GM3 in MVs from plasma of healthy human donors. Similar findings were found in MVs from cell culture supernatants of murine neuronal cells. Furthermore we demonstrated that PrPSc is released from infected murine neuronal cells in association with plasma membrane-derived MVs and that PrPSc-bearing MVs are infectious both in vitro and in vivo. The data suggest that MVs may contribute both to the intercellular mechanism(s) of PrPC diffusion and signaling as well as to the process of prion spread and neuroinvasion. PMID:19337375

  19. DERIVING PLASMA DENSITIES AND ELEMENTAL ABUNDANCES FROM SERTS DIFFERENTIAL EMISSION MEASURE ANALYSIS

    SciTech Connect

    Schmelz, J. T.; Kimble, J. A.; Saba, J. L. R.

    2012-09-20

    We use high-resolution spectral emission line data obtained by the SERTS instrument during three rocket flights to demonstrate a new approach for constraining electron densities of solar active region plasma. We apply differential emission measure (DEM) forward-fitting techniques to characterize the multithermal solar plasma producing the observed EUV spectra, with constraints on the high-temperature plasma from the Yohkoh Soft X-ray Telescope. In this iterative process, we compare line intensities predicted by an input source distribution to observed line intensities for multiple iron ion species, and search a broad range of densities to optimize {chi}{sup 2} simultaneously for the many available density-sensitive lines. This produces a density weighted by the DEM, which appears to be useful for characterizing the bulk of the emitting plasma over a significant range of temperature. This 'DEM-weighted density' technique is complementary to the use of density-sensitive line ratios and less affected by uncertainties in atomic data and ionization fraction for any specific line. Once the DEM shape and the DEM-weighted density have been established from the iron lines, the relative elemental abundances can be determined for other lines in the spectrum. We have also identified spectral lines in the SERTS wavelength range that may be problematic.

  20. Deriving Plasma Densities and Elemental Abundances from SERTS Differential Emission Measure Analysis

    NASA Technical Reports Server (NTRS)

    Schmelz, J. T.; Kimble, J. A.; Saba, J. L. R.

    2012-01-01

    We use high-resolution spectral emission line data obtained by the SERTS instrument during three rocket flights to demonstrate a new approach for constraining electron densities of solar active region plasma.We apply differential emission measure (DEM) forward-fitting techniques to characterize the multithermal solar plasma producing the observed EUV spectra, with constraints on the high-temperature plasma from the Yohkoh Soft X-ray Telescope. In this iterative process, we compare line intensities predicted by an input source distribution to observed line intensities for multiple iron ion species, and search a broad range of densities to optimize chi-square simultaneously for the many available density-sensitive lines. This produces a density weighted by the DEM, which appears to be useful for characterizing the bulk of the emitting plasma over a significant range of temperature. This "DEM-weighted density" technique is complementary to the use of density-sensitive line ratios and less affected by uncertainties in atomic data and ionization fraction for any specific line. Once the DEM shape and the DEM-weighted density have been established from the iron lines, the relative elemental abundances can be determined for other lines in the spectrum. We have also identified spectral lines in the SERTS wavelength range that may be problematic

  1. Plasma membrane characterization, by scanning electron microscopy, of multipotent myoblasts-derived populations sorted using dielectrophoresis

    SciTech Connect

    Muratore, Massimo; Mitchell, Steve; Waterfall, Martin

    2013-09-06

    Highlights: •Dielectrophoretic separation/sorting of multipotent cells. •Plasma membrane microvilli structure of C2C12 and fibroblasts by SEM microscopy. •Cell cycle determination by Ki-67 in DEP-sorted cells. •Plasma membrane differences responsible for changes in membrane capacitance. -- Abstract: Multipotent progenitor cells have shown promise for use in biomedical applications and regenerative medicine. The implementation of such cells for clinical application requires a synchronized, phenotypically and/or genotypically, homogenous cell population. Here we have demonstrated the implementation of a biological tag-free dielectrophoretic device used for discrimination of multipotent myoblastic C2C12 model. The multipotent capabilities in differentiation, for these cells, diminishes with higher passage number, so for cultures above 70 passages only a small percentage of cells is able to differentiate into terminal myotubes. In this work we demonstrated that we could recover, above 96% purity, specific cell types from a mixed population of cells at high passage number without any biological tag using dielectrophoresis. The purity of the samples was confirmed by cytometric analysis using the cell specific marker embryonic myosin. To further investigate the dielectric properties of the cell plasma membrane we co-culture C2C12 with similar size, when in suspension, GFP-positive fibroblast as feeder layer. The level of separation between the cell types was above 98% purity which was confirmed by flow cytometry. These levels of separation are assumed to account for cell size and for the plasma membrane morphological differences between C2C12 and fibroblast unrelated to the stages of the cell cycle which was assessed by immunofluorescence staining. Plasma membrane conformational differences were further confirmed by scanning electron microscopy.

  2. Moment Approach to Deriving a Unified Parallel Viscous Stress in Magnetized Plasmas

    NASA Astrophysics Data System (ADS)

    Ji, Jeong-Young; Held, Eric D.

    2009-06-01

    In the moment approach, a parallel heat flux and a viscous stress are derived for arbitrary collisionality, which is becoming increasingly important in emerging concept devices. This derivation improves upon previous derivations by using the full linearized collision operators instead of the pitch-angle scattering operator and also by including the ion-electron collision operator. The parallel viscous stress can be computed by integrating thermodynamic drives along a magnetic field line weighted by kernel functions that are simple linear combinations of exponential functions. The convergence of the ion viscous stress is verified for sinusoidally varying drives with increasing number of moments.

  3. Characterization of human-induced pluripotent stem cell-derived cardiomyocytes: bioenergetics and utilization in safety screening.

    PubMed

    Rana, Payal; Anson, Blake; Engle, Sandra; Will, Yvonne

    2012-11-01

    Cardiotoxicity remains the number one reason for drug withdrawal from the market, and Food and Drug Administration issued black box warnings, thus demonstrating the need for more predictive preclinical safety screening, especially early in the drug discovery process when much chemical substrate is available. Whereas human-ether-a-go-go related gene screening has become routine to mitigate proarrhythmic risk, the development of in vitro assays predicting additional on- and off-target biochemical toxicities will benefit from cellular models exhibiting true cardiomyocyte characteristics such as native tissue-like mitochondrial activity. Human stem cell-derived tissue cells may provide such a model. This hypothesis was tested using a combination of flux analysis, gene and protein expression, and toxicity-profiling techniques to characterize mitochondrial function in induced pluripotent stem cell (iPSC) derived human cardiomyocytes in the presence of differing carbon sources over extended periods in cell culture. Functional analyses demonstrate that iPSC-derived cardiomyocytes are (1) capable of utilizing anaerobic or aerobic respiration depending upon the available carbon substrate and (2) bioenergetically closest to adult heart tissue cells when cultured in galactose or galactose supplemented with fatty acids. We utilized this model to test a variety of kinase inhibitors with known clinical cardiac liabilities for their potential toxicity toward these cells. We found that the kinase inhibitors showed a dose-dependent toxicity to iPSC cardiomyocytes grown in galactose and that oxygen consumption rates were significantly more affected than adenosine triphosphate production. Sorafenib was found to have the most effect, followed by sunitinib, dasatinib, imatinib, lapatinib, and nioltinib. PMID:22843568

  4. Application of first-derivative, ratio derivative spectrophotometry, TLC-densitometry and spectrofluorimetry for the simultaneous determination of telmisartan and hydrochlorothiazide in pharmaceutical dosage forms and plasma.

    PubMed

    Bebawy, Lories I; Abbas, Samah S; Fattah, Laila A; Refaat, Heba H

    2005-10-01

    Four sensitive methods are described for the direct determination of telmisartan (TELM) and hydrochlorothiazide (HCT) in combined dosage forms without prior separation. The first method is a first derivative spectophotometry (1D) using a zero- crossing technique of measurement at 241.6 and 227.6 nm for TELM and HCT, respectively. The second method is the first derivative of ratio spectrophotometry (1DD) where the amplitudes were measured at 242.7 nm for TELM and 274.9 nm for HCT. The third method is based on TLC separation of the two drugs followed by the densitometric measurements of their spots at 295 and 225 nm for TELM and HCT, respectively. The separation was carried out on silica gel 60 F254 using butanol: ammonia 25% (8:2 v/v) as mobile phase. The fourth method is spectrofluorimetric determination of TELM, depending on measuring the native fluorescence of the drug in 1 M sodium hydroxide at lambda excitation 230 nm and emission at 365 nm. The proposed methods were applied successfully for the determination of the two drugs in bulk powder and in pharmaceutical formulations. The spectrofluorimetric method was utilized for the analysis of TELM in human plasma. PMID:16129437

  5. Analysis of tumor-derived DNA in plasma and bone marrow fluid in lung cancer patients.

    PubMed

    Goto, Taichiro; Hirotsu, Yosuke; Oyama, Toshio; Amemiya, Kenji; Omata, Masao

    2016-03-01

    Liquid biopsies such as circulating tumor DNA in plasma and disseminated tumor cells in the bone marrow are currently available. However, it is unclear which types of samples are appropriate for detecting tumor DNA in these biopsies. Here, we collected primary tumors, pulmonary venous blood, peripheral blood, and rib bone marrow fluid from 10 lung cancer patients. Targeted deep sequencing was performed to identify mutations across 70 specimens. As a result, a total of 43 mutations were identified in the primary tumors. The mutation in the tumors was also identified in circulating tumor DNA in the pulmonary venous and peripheral blood in two patients. These patients showed poor prognosis, as compared to the other patients. However, no mutation was identified in the bone marrow in any of the patients. These results demonstrated that circulating tumor DNA in plasma is more sensitive and clinically useful as a biomarker as compared to DNA in bone marrow fluid. PMID:26897174

  6. Platelet-rich Plasma and Bone Marrow-derived Mesenchymal Stem Cells in Sports Medicine.

    PubMed

    Gobbi, Alberto; Fishman, Matthew

    2016-06-01

    Regenerative medicine is a fast-growing field in orthopedic sports medicine. Platelet-rich plasma contains multiple factors that have been shown to augment healing, thereby stimulating its use in multiple areas of acute and chronic injuries. Mesenchymal stem cells have pluripotent potential to form into tissues pertinent to orthopedics, such as cartilage and bone. As such, there is been a surge in the research directed toward steering those stem cells into a particular lineage as part of treatment for a variety of soft-tissue, cartilage, and bone pathologies. Overall, there are promising reports of their potential success, but there is a need for continued investigation into the efficacy of platelet-rich plasma and stem cells in sports medicine. PMID:27135289

  7. Practical silicon deposition rules derived from silane monitoring during plasma-enhanced chemical vapor depositiona)

    NASA Astrophysics Data System (ADS)

    Bartlome, Richard; De Wolf, Stefaan; Demaurex, Bénédicte; Ballif, Christophe; Amanatides, Eleftherios; Mataras, Dimitrios

    2015-05-01

    We clarify the difference between the SiH4 consumption efficiency η and the SiH4 depletion fraction D, as measured in the pumping line and the actual reactor of an industrial plasma-enhanced chemical vapor deposition system. In the absence of significant polysilane and powder formation, η is proportional to the film growth rate. Above a certain powder formation threshold, any additional amount of SiH4 consumed translates into increased powder formation rather than into a faster growing Si film. In order to discuss a zero-dimensional analytical model and a two-dimensional numerical model, we measure η as a function of the radio frequency (RF) power density coupled into the plasma, the total gas flow rate, the input SiH4 concentration, and the reactor pressure. The adjunction of a small trimethylboron flow rate increases η and reduces the formation of powder, while the adjunction of a small disilane flow rate decreases η and favors the formation of powder. Unlike η, D is a location-dependent quantity. It is related to the SiH4 concentration in the plasma cp, and to the phase of the growing Si film, whether the substrate is glass or a c-Si wafer. In order to investigate transient effects due to the RF matching, the precoating of reactor walls, or the introduction of a purifier in the gas line, we measure the gas residence time and acquire time-resolved SiH4 density measurements throughout the ignition and the termination of a plasma.

  8. Practical silicon deposition rules derived from silane monitoring during plasma-enhanced chemical vapor deposition

    SciTech Connect

    Bartlome, Richard De Wolf, Stefaan; Demaurex, Bénédicte; Ballif, Christophe; Amanatides, Eleftherios; Mataras, Dimitrios

    2015-05-28

    We clarify the difference between the SiH{sub 4} consumption efficiency η and the SiH{sub 4} depletion fraction D, as measured in the pumping line and the actual reactor of an industrial plasma-enhanced chemical vapor deposition system. In the absence of significant polysilane and powder formation, η is proportional to the film growth rate. Above a certain powder formation threshold, any additional amount of SiH{sub 4} consumed translates into increased powder formation rather than into a faster growing Si film. In order to discuss a zero-dimensional analytical model and a two-dimensional numerical model, we measure η as a function of the radio frequency (RF) power density coupled into the plasma, the total gas flow rate, the input SiH{sub 4} concentration, and the reactor pressure. The adjunction of a small trimethylboron flow rate increases η and reduces the formation of powder, while the adjunction of a small disilane flow rate decreases η and favors the formation of powder. Unlike η, D is a location-dependent quantity. It is related to the SiH{sub 4} concentration in the plasma c{sub p}, and to the phase of the growing Si film, whether the substrate is glass or a c-Si wafer. In order to investigate transient effects due to the RF matching, the precoating of reactor walls, or the introduction of a purifier in the gas line, we measure the gas residence time and acquire time-resolved SiH{sub 4} density measurements throughout the ignition and the termination of a plasma.

  9. Origin and development of plasma membrane derived invaginations in Vinca rosea l.

    NASA Technical Reports Server (NTRS)

    Mahlberg, P.; Walkinshaw, C.; Olson, K.

    1971-01-01

    The occurrence, morphology, and possible ontogeny of plasma-membrane-related structures are described which can develop into invaginations or intravacuolar formations. An underlying study of meristematic tissues from the shoot of Vinca rosea supports the interpretation that endocytosis does occur in plant cells and that it is appropriate to refer to these structures as endocytoses. The function of these invaginations or their content remains to be elucidated.

  10. Plasma membrane characterization, by scanning electron microscopy, of multipotent myoblasts-derived populations sorted using dielectrophoresis.

    PubMed

    Muratore, Massimo; Mitchell, Steve; Waterfall, Martin

    2013-09-01

    Multipotent progenitor cells have shown promise for use in biomedical applications and regenerative medicine. The implementation of such cells for clinical application requires a synchronized, phenotypically and/or genotypically, homogenous cell population. Here we have demonstrated the implementation of a biological tag-free dielectrophoretic device used for discrimination of multipotent myoblastic C2C12 model. The multipotent capabilities in differentiation, for these cells, diminishes with higher passage number, so for cultures above 70 passages only a small percentage of cells is able to differentiate into terminal myotubes. In this work we demonstrated that we could recover, above 96% purity, specific cell types from a mixed population of cells at high passage number without any biological tag using dielectrophoresis. The purity of the samples was confirmed by cytometric analysis using the cell specific marker embryonic myosin. To further investigate the dielectric properties of the cell plasma membrane we co-culture C2C12 with similar size, when in suspension, GFP-positive fibroblast as feeder layer. The level of separation between the cell types was above 98% purity which was confirmed by flow cytometry. These levels of separation are assumed to account for cell size and for the plasma membrane morphological differences between C2C12 and fibroblast unrelated to the stages of the cell cycle which was assessed by immunofluorescence staining. Plasma membrane conformational differences were further confirmed by scanning electron microscopy. PMID:23933253

  11. A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease

    PubMed Central

    Barascuk, Natasha; Genovese, Federica; Larsen, Lise; Byrjalsen, Inger; Zheng, Qinlong; Sun, Shu; Hosbond, Susanne; Poulsen, Tina S; Diederichsen, Axel; Jensen, Jesper M; Mickley, Hans; Register, Thomas C; Rasmussen, Lars M; Leeming, Diana J; Christiansen, Claus; Karsdal, Morten A

    2013-01-01

    Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in macrophage rich areas. The aim of the current study was to develop an immunoassay to detect a specific MMP-12 derived versican degradation fragment (VCANM) and assess its potential as a biomarker for extracellular matrix remodelling in atherosclerosis. A mouse monoclonal antibody raised against VCANM was used for the development of a competitive ELISA for detection of the fragment in plasma. VCANM was measured in plasma of patients with different levels of heart diseases. Patients experiencing I) acute coronary syndrome, II) stable ischemic heart disease and III) demonstrating high levels of coronary calcium deposits had significantly higher plasma levels of VCANM compared to a control group of individuals with no detectable coronary calcium deposits. VCANM was also detected by immunohistochemistry in coronary artery sections of patients with different degrees of atherosclerosis. VCANM ability to separate patients with atherosclerotic diseases from healthy individuals suggested VCANM as a potential biomarker for the pathological arterial matrix remodelling associated with atherosclerosis. PMID:23573348

  12. Size-exclusion chromatography as a stand-alone methodology identifies novel markers in mass spectrometry analyses of plasma-derived vesicles from healthy individuals

    PubMed Central

    de Menezes-Neto, Armando; Sáez, María José Fidalgo; Lozano-Ramos, Inés; Segui-Barber, Joan; Martin-Jaular, Lorena; Ullate, Josep M. Estanyol; Fernandez-Becerra, Carmen; Borrás, Francesc E.; del Portillo, Hernando A.

    2015-01-01

    Plasma-derived vesicles hold a promising potential for use in biomedical applications. Two major challenges, however, hinder their implementation into translational tools: (a) the incomplete characterization of the protein composition of plasma-derived vesicles, in the size range of exosomes, as mass spectrometric analysis of plasma sub-components is recognizably troublesome and (b) the limited reach of vesicle-based studies in settings where the infrastructural demand of ultracentrifugation, the most widely used isolation/purification methodology, is not available. In this study, we have addressed both challenges by carrying-out mass spectrometry (MS) analyses of plasma-derived vesicles, in the size range of exosomes, from healthy donors obtained by 2 alternative methodologies: size-exclusion chromatography (SEC) on sepharose columns and Exo-Spin™. No exosome markers, as opposed to the most abundant plasma proteins, were detected by Exo-Spin™. In contrast, exosomal markers were present in the early fractions of SEC where the most abundant plasma proteins have been largely excluded. Noticeably, after a cross-comparative analysis of all published studies using MS to characterize plasma-derived exosomes from healthy individuals, we also observed a paucity of “classical exosome markers.” Independent of the isolation method, however, we consistently identified 2 proteins, CD5 antigen-like (CD5L) and galectin-3-binding protein (LGALS3BP), whose presence was validated by a bead-exosome FACS assay. Altogether, our results support the use of SEC as a stand-alone methodology to obtain preparations of extracellular vesicles, in the size range of exosomes, from plasma and suggest the use of CD5L and LGALS3BP as more suitable markers of plasma-derived vesicles in MS. PMID:26154623

  13. Pharmacokinetics, Safety, and Antiviral Effects of Hypericin, a Derivative of St. John's Wort Plant, in Patients with Chronic Hepatitis C Virus Infection

    PubMed Central

    Jacobson, Jeffrey M.; Feinman, Lawrence; Liebes, Leonard; Ostrow, Nancy; Koslowski, Victoria; Tobia, Alfonso; Cabana, Bernard E.; Lee, Dong-Hun; Spritzler, John; Prince, Alfred M.

    2001-01-01

    Hypericin is a natural derivative of the common St. Johns wort plant, Hypericum perforatum. It has in vitro activity against several viruses, including bovine diarrhea virus, a pestivirus with structural similarities to hepatitis C virus (HCV). We conducted a phase I dose escalation study to determine the safety and antiviral activity of hypericin in patients with chronic HCV infection. The first 12 patients received an 8-week course of 0.05 mg of hypericin per kg of body weight orally once a day; 7 patients received an 8-week course of 0.10 mg/kg orally once a day. At the end of the 8-week period of treatment, no subject had a change of plasma HCV RNA level of more than 1.0 log10. Five of 12 subjects receiving the 0.05-mg/kg/day dosing schedule and 6 of 7 subjects receiving the 0.10-mg/kg/day dosing schedule developed phototoxic reactions. No other serious adverse events associated with hypericin use occurred. The pharmacokinetic data revealed a long elimination half-life (mean values of 36.1 and 33.8 h, respectively, for the doses of 0.05 and 0.1 mg/kg) and mean area under the curve determinations of 1.5 and 3.1 μg/ml × hr, respectively. In sum, hypericin given orally in doses of 0.05 and 0.10 mg/kg/d caused considerable phototoxicity and had no detectable anti-HCV activity in patients with chronic HCV infection. PMID:11158749

  14. Dry-heat treatment process for enhancing viral safety of an antihemophilic factor VIII concentrate prepared from human plasma.

    PubMed

    Kim, In Seop; Choi, Yong Woon; Kang, Yong; Sung, Hark Mo; Shin, Jeong Sup

    2008-05-01

    Viral safety is a prerequisite for manufacturing clinical antihemophilic factor VIII concentrates from human plasma. With particular regard to the hepatitis A virus (HAV), a terminal dry-heat treatment (100 degrees for 30 min) process, following lyophilization, was developed to improve the virus safety of a solvent/detergent-treated antihemophilic factor VIII concentrate. The loss of factor VIII activity during dry-heat treatment was of about 5%. No substantial changes were observed in the physical and biochemical characteristics of the dry-heat-treated factor VIII compared with those of the factor VIII before dry-heat treatment. The dry-heat-treated factor VIII was stable for up to 24 months at 4oC. The dry-heat treatment after lyophilization was an effective process for inactivating viruses. The HAV, murine encephalomyocarditis virus (EMCV), and human immunodeficiency virus (HIV) were completely inactivated to below detectable levels within 10 min of the dry-heat treatment. Bovine herpes virus (BHV) and bovine viral diarrhea virus (BVDV) were potentially sensitive to the treatment. However porcine parvovirus (PPV) was slightly resistant to the treatment. The log reduction factors achieved during lyophilization and dry-heat treatment were > or =5.55 for HAV, > or =5.87 for EMCV, > or =5.15 for HIV, 6.13 for BHV, 4.46 for BVDV, and 1.90 for PPV. These results indicate that dry-heat treatment improves the virus safety of factor VIII concentrates, without destroying the activity. Moreover, the treatment represents an effective measure for the inactivation of non-lipid-enveloped viruses, in particular HAV, which is resistant to solvent/detergent treatment. PMID:18633304

  15. Novel coumarin modified GLP-1 derivatives with enhanced plasma stability and prolonged in vivo glucose-lowering ability

    PubMed Central

    Han, Jing; Sun, Lidan; Huang, Xun; Li, Zheng; Zhang, Chenyu; Qian, Hai; Huang, Wenlong

    2014-01-01

    Background and Purpose The short biological half-life limits the therapeutic use of glucagon-like peptide-1 (GLP-1) and chemical modification to improve the interaction of peptides with serum albumin represents an effective strategy to develop long-acting peptide analogues. Coumarin, a natural product, is known to bind tightly to plasma proteins and possesses many biological activities. Therefore, we designed and synthesized a series of coumarin-modified GLP-1 derivatives, hypothesizing that conjugation with coumarin would retain the therapeutic effects and prolong the biological half-life of the conjugates. Experimental Approach Four cysteine-modified GLP-1 analogues (1–4) were prepared using Gly8-GLP-1(7–36)-NH2 peptide as a starting point. These analogues were conjugated with two coumarin maleimides to yield eight compounds (conjugates 6–13) for testing. Activation of human GLP-1 receptors, stability to enzymic inactivation in plasma and binding to human albumin were assessed in vitro. In vivo, effects on oral glucose tolerance tests (OGTT) in rats and on blood glucose levels in db/db mice were studied. Key Results Most conjugates showed well preserved receptor activation efficacy, enhanced albumin-binding properties and improved in vitro plasma stability and conjugate 7 was selected to undergo further assessment. In rats, conjugate 7 had a longer circulating t1/2 than exendin-4 or liraglutide. A prolonged antidiabetic effect of conjugate 7 was observed after OGTT in rats and a prolonged hypoglycaemic effect in db/db mice. Conclusions and Implications Cysteine-specific coumarin conjugation with GLP-1 offers a useful approach to the development of long-acting incretin-based antidiabetic agents. Conjugate 7 is a promising long-lasting GLP-1 derivative deserving further investigation. PMID:25039358

  16. Plasma-derived and synthetic high-density lipoprotein inhibit tissue factor in endothelial cells and monocytes.

    PubMed

    Ossoli, Alice; Remaley, Alan T; Vaisman, Boris; Calabresi, Laura; Gomaraschi, Monica

    2016-01-15

    HDL (high-density lipoproteins) exert anti-thrombotic activities by preventing platelet adhesion and activation and by stimulating the protein C pathway and fibrinolysis. The aim of the present study was to assess the effect of plasma-derived and synthetic HDL on endothelial and monocyte expression of TF (tissue factor), the primary initiator of coagulation. HDL inhibited TF expression and activity in stimulated endothelial cells and monocytes in a dose-dependent way. Synthetic HDL fully retain the ability to inhibit TF expression in a dose-dependent manner; lipid-free apoA-I (apolipoprotein A-I) was not effective and neither was sphingosine 1-phosphate involved. HDL-mediated TF inhibition was due to a modulation of cellular cholesterol content through the interaction with SR-BI (scavenger receptor BI); downstream, HDL inhibited the activation of p38 MAPK (mitogen-activated protein kinase) and the repression of the PI3K (phosphoinositide 3-kinase) pathway responsible for TF expression. In vivo, human apoA-I-transgenic mice displayed a reduced aortic TF expression compared with wild-type animals and TF plasma levels were increased in subjects with low HDL-C (HDL-cholesterol) levels compared with high HDL-C subjects. Thus the anti-thrombotic activity of HDL could also be mediated by the inhibition of TF expression and activity in endothelial cells and monocytes; synthetic HDL retain the inhibitory activity of plasma-derived HDL, supporting the hypothesis that synthetic HDL infusion may be beneficial in the setting of acute coronary syndrome. PMID:26556891

  17. Increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acid levels in human plasma after a single dose of long-chain omega-3 PUFA

    PubMed Central

    Schuchardt, Jan Philipp; Schneider, Inga; Willenberg, Ina; Yang, Jun; Hammock, Bruce D.; Hahn, Andreas; Schebb, Nils Helge

    2014-01-01

    Introduction Several supplementation studies with long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) describe an increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acids in blood, while changes in levels of other LC n-3 and n-6 PUFA-derived oxylipins were minor. In order to investigate the kinetics of changes in oxylipin levels in response to LC n-3 PUFA ingestion, we conducted a single dose treatment study with healthy subjects. Subjects and methods In the present kinetic study, we compared patterns of hydroxy, epoxy and dihydroxy fatty acids in plasma of 6 healthy men before and after 6, 8, 24, and 48 h of fish oil (1008 mg EPA and 672 mg DHA) ingestion. Levels of EPA- as well as other LC PUFA-derived hydroxy, epoxy and dihydroxy fatty acids were analyzed in plasma by LC–MS. Additionally, levels of these oxylipins were compared with their parent PUFA levels in plasma phospholipids. Results All EPA-derived oxylipin levels were significantly increased 6 h after LC n-3 PUFA ingestion and gradually drop thereafter reaching the baseline levels about 48 h after treatment. The relative increase in EPA plasma phospholipid levels highly correlated with the increase of plasma EPA-derived oxylipin levels at different time points. In contrast, plasma levels of arachidonic acid- and DHA-derived oxylipins as well as parent PUFA levels in plasma phospholipids were hardly changed. Discussion and conclusions Our findings demonstrate that a single dose of LC n-3 PUFAs can rapidly induce a shift in the EPA oxylipin profile of healthy subjects within a few hours. Taking the high biological activity of the EPA-derived epoxy fatty acids into account, even short-term treatment with LC n-3 PUFAs may cause systemic effects, which warrant further investigation. PMID:24667634

  18. Plasma Brain-Derived Neurotrophic Factor and Reverse Dipping Pattern of Nocturnal Blood Pressure in Patients with Cardiovascular Risk Factors

    PubMed Central

    Kadoya, Manabu; Koyama, Hidenori; Kanzaki, Akinori; Kurajoh, Masafumi; Hatayama, Miki; Shiraishi, Jun; Okazaki, Hirokazu; Shoji, Takuhito; Moriwaki, Yuji; Yamamoto, Tetsuya; Inaba, Masaaki; Namba, Mitsuyoshi

    2014-01-01

    Context Basic studies have shown that brain-derived neurotrophic factor (BDNF) has critical roles in the survival, growth, maintenance, and death of central and peripheral neurons, while it is also involved in regulation of the autonomic nervous system. Furthermore, recent clinical studies have suggested potential role of plasma BDNF in the circulatory system. Objective We investigated the mutual relationships among plasma BDNF, patterns of nocturnal blood pressure changes (dippers, non-dippers, extra-dippers, and reverse-dippers), and cardiac autonomic function as determined by heart rate variability (HRV). Design This was a cross-sectional study of patients registered in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA) Study from October 2010 to November 2012. Patients Two-hundred fifty patients with 1 or more cardiovascular risk factor(s) (obesity, smoking, presence of cardiovascular event history, hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease) were enrolled. Results Plasma BDNF levels (natural logarithm transformed) were significantly (p = 0.001) lower in reverse-dipper patients (7.18±0.69 pg/ml, mean ± SD, n = 36) as compared to dippers (7.86±0.86 pg/ml, n = 100). Multiple logistic regression analysis showed that BDNF (odds ratios: 0.417, 95% confidence interval: 0.228–0.762, P = 0.004) was the sole factor significantly and independently associated with the reverse-dippers as compared with dippers. Furthermore, plasma BDNF level was significantly and positively correlated with the time-domain (SDNN, SDANN5, CVRR) and frequency-domain (LF) of HRV parameters. Finally, multiple logistic regression analyses showed that the relationship between plasma BDNF and the reverse-dippers was weakened, yet remained significant or borderline significant even after adjusting for HRV parameters. Conclusions Low plasma BDNF was independently associated with patients showing a reverse-dipper pattern of nocturnal blood pressure

  19. Gyromap for a two-dimensional Hamiltonian fluid model derived from Braginskii's closure for magnetized plasmas

    SciTech Connect

    Izacard, O.; Chandre, C.; Tassi, E.; Ciraolo, G.

    2011-06-15

    We consider a plasma described by means of a two-dimensional fluid model across a constant but non-uniform magnetic field B=B(x,y)z. The dynamical evolution of the density and the vorticity takes into account the interchange instability and magnetic field inhomogeneities. First, in order to describe the finite Larmor radius effects, we apply the gyromap to build a Hamiltonian model with ion temperature from a cold-ion model. Second, we show that the gyromap is justified using Braginskii's closure for the stress tensor as well as an apt ordering on the fluctuating quantities.

  20. The effect of a single standard of engineering safety (S3E) on the airworthiness of military derivative aircraft

    NASA Astrophysics Data System (ADS)

    Lasaxon, Victor Manuel

    Scope and method of study. The purpose of this experimental study was to examine the effects of applying a single standard of engineering safety (S3E) on the airworthiness of military derivative aircraft. For the purpose of this study, S3E is defined as the use of commercial standards for airworthiness in embodied in Federal Aviation Regulation (FAR) 121 and Federal Aviation Administration (FAA) Order 8300.10, then tailored and applied to the Department of Defense (DOD). Using a S3E audit normally used to inspect airlines but specially tailored to the military two randomly selected military units were pre-tested. Although the random selection was blind to the study it is known that the units were of different services but operated the same type of commercially built and certified military derivative aircraft. It is also known that their force of strength and fleet size were the same. After the pre-test, one unit was treated by exposure to S3E commercial standards for airworthiness per FAR Part 121 and FAA Order 8300.10 and the other unit was not. After 90 days, both units were post-tested. Percent change comparison on the pre and post test as well as the chi squared technique was used to analyze the data. Findings and conclusions. The results of the study indicate that the treated unit experienced significant improvement in airworthiness compliance and the control unit did not. It was concluded that S3E had a positive effect in this first of its kind study, but further and expanded research needs to continue.

  1. A comparison of skin delivery of ferulic acid and its derivatives: evaluation of their efficacy and safety.

    PubMed

    Zhang, Li-Wen; Al-Suwayeh, Saleh A; Hsieh, Pei-Wen; Fang, Jia-You

    2010-10-31

    Ferulic acid (FA) can be used as an antioxidant to prevent damage from ultraviolet (UV) radiation and skin carcinogenesis. To this end, the feasibility of the skin absorption of FA and its derivatives was evaluated in the present study. The percutaneous absorption of five compounds into/across porcine skin was measured and compared using Franz diffusion cells. The skin delivery from pH 6 and 9.9 buffers was the highest for ferulic acid ethyl ether (FAEE), followed by coniferyl aldehyde (CD), coniferyl alcohol (CA), FA, and 3-hydroxy-4-methoxycinnamic acid (HMA). The skin deposition and flux of FAEE with a pH 6 buffer were 136 nmol/g and 26 nmol/cm(2)/h, respectively. No significant difference in permeation profiles was observed between the two pH buffers. According to permeation via the skin with different treatments (delipidization, ethanol, and oleic acid treatments), it was determined that the lipid bilayers in the stratum corneum (SC) comprised the predominant barrier for FA permeation. On the other hand, FAEE could easily partition into and penetrate across the skin through intercellular pathways. Nude mouse was used as an in vivo animal model to examine the amount of permeants remaining in the skin. The in vivo skin deposition was generally correlated with the in vitro results. The in vivo skin deposition of FAEE (145 nmol/g) was comparable to that of CD (150 nmol/g). The safety study which examined transepidermal water loss (TEWL), erythema, and the skin pH value demonstrated that the topical application of FA and related compounds for up to 24h did not cause skin irritation. It can be concluded that topical delivery may serve as an efficient and safe route for FA and its derivatives against photodamage. PMID:20692328

  2. Insulin stimulates the generation from hepatic plasma membranes of modulators derived from an inositol glycolipid.

    PubMed Central

    Saltiel, A R; Cuatrecasas, P

    1986-01-01

    Insulin binding to plasma membrane receptors results in the generation of substances that acutely mimic the actions of the hormone on certain target enzymes. Two such substances, which modulate the activity of the high-affinity cAMP phosphodiesterase (EC 3.1.4.17), have been purified from hepatic plasma membranes. The two have similar properties and activities but can be resolved by ion-exchange chromatography and high-voltage electrophoresis. They exhibit a net negative charge, even at pH 1.9, and an apparent molecular weight of approximately 1400. The generation of these substances from membranes by insulin can be reproduced by addition of a phosphatidylinositol-specific phospholipase C purified from Staphylococcus aureus. This enzyme is known to selectively hydrolyze phosphatidylinositol and release from membranes several proteins that are covalently linked to phosphatidylinositol by a glycan anchor. Both enzyme-modulating substances appear to be generated by the phosphodiesterase cleavage of a phosphatidylinositol-containing glycolipid precursor that has been characterized by thin-layer chromatography. Some of the chemical properties of these substances have been examined. They appear to be related complex carbohydrate-phosphate substances containing glucosamine and inositol. These findings suggest that insulin may activate a selective phospholipase activity that hydrolyzes a membrane phospholipid, releasing a carbohydrate-containing molecule that regulates cAMP phosphodiesterase and perhaps other insulin-sensitive enzymes. PMID:3016721

  3. Influence of pressure derivative of partition function on thermodynamic properties of non-local thermodynamic equilibrium thermal plasma

    NASA Astrophysics Data System (ADS)

    Singh, Gurpreet; Sharma, Rohit; Singh, Kuldip

    2015-09-01

    Thermodynamic properties (compressibility coefficient Z γ , specific heat at constant volume c v , adiabatic coefficient γ a , isentropic coefficient γ i s e n , and sound speed c s ) of non-local thermodynamic equilibrium hydrogen thermal plasma have been investigated for different values of pressure and non-equilibrium parameter θ (=Te/Th) in the electron temperature range from 6000 K to 60 000 K. In order to estimate the influence of pressure derivative of partition function on thermodynamic properties, two cases have been considered: (a) in which pressure derivative of partition function is taken into account in the expressions and (b) without pressure derivative of partition function in their expressions. Here, the case (b) represents expressions already available in literature. It has been observed that the temperature from which pressure derivative of partition function starts influencing a given thermodynamic property increases with increase of pressure and non-equilibrium parameter θ. Thermodynamic property in the case (a) is always greater than its value in the case (b) for compressibility coefficient and specific heat at constant volume, whereas for adiabatic coefficient, isentropic coefficient, and sound speed, its value in the case (a) is always less than its value in the case (b). For a given value of θ, the relationship of compressibility coefficient with degree of ionization depends upon pressure in the case (a), whereas it is independent of pressure in the case (b). Relative deviation between the two cases shows that the influence of pressure derivative of partition function is significantly large and increases with the augmentation of pressure and θ for compressibility coefficient, specific heat at constant volume, and adiabatic coefficient, whereas for isentropic coefficient and sound speed, it is marginal even at high values of pressure and non-equilibrium parameter θ.

  4. [Genetically modified food (food derived from biotechnology): current and future trends in public acceptance and safety assessment].

    PubMed

    Nishiura, Hiroshi; Imai, Hirohisa; Nakao, Hiroyuki; Tsukino, Hiromasa; Kuroda, Yoshiki; Katoh, Takahiko

    2002-11-01

    Current and future trends regarding genetically modified (GM) crops and food stuffs were reviewed, with a particular focus on public acceptance and safety assessment. While GM foods, foods derived from biotechnology, are popular with growers and producers, they are still a matter of some concern among consumers. In fact, our recent surveys showed that Japanese consumers had become uneasy about the potential health risks of genetically modified foods. Many Japanese consumers have only vague ideas about the actual health risks, and they appear to be making decisions simply by rejecting GM food because of non-informed doubts. Although the debate about GM foods has increased in the mass media and scientific journals, few articles concerning direct studies on the potential toxicity or adverse health effects of GM foods have appeared. The roles of relevant international regulatory bodies in ensuring that GM crops and food are safe are therefore have summarized. Finally, the current debate on use of GM crops in agriculture and future trends for development of GM foods with enriched nutrients, better functionality, and medicinal ingredients, which will be of direct benefit to the consumer, are covered. PMID:12508467

  5. Long term effect and safety of Wharton's jelly-derived mesenchymal stem cells on type 2 diabetes

    PubMed Central

    Hu, Jianxia; Wang, Yangang; Gong, Huimin; Yu, Chundong; Guo, Caihong; Wang, Fang; Yan, Shengli; Xu, Hongmei

    2016-01-01

    Cellular therapies offer novel opportunities for the treatment of type 2 diabetes mellitus (T2DM). The present study evaluated the long-term efficacy and safety of infusion of Wharton's jelly-derived mesenchymal stem cells (WJ-MSC) on T2DM. A total of 61 patients with T2DM were randomly divided into two groups on the basis of basal therapy; patients in group I were administered WJ-MSC intravenous infusion twice, with a four-week interval, and patients in group II were treated with normal saline as control. During the 36-month follow-up period, the occurrence of any adverse effects and the results of clinical and laboratory examinations were recorded and evaluated. The lack of acute or chronic adverse effects in group I was consistent with group II.. Blood glucose, glycosylated hemoglobin, C-peptide, homeostasis model assessment of pancreatic islet β-cell function and incidence of diabetic complications in group I were significantly improved, as compared with group II during the 36-month follow-up. The results of the present study demonstrated that infusion of WJ-MSC improved the function of islet β-cells and reduced the incidence of diabetic complications, although the precise mechanisms are yet to be elucidated. The infusion of WJ-MSC may be an effective option for the treatment of patients with type 2 diabetes. PMID:27588104

  6. Preliminary safety evaluation of a taurocholate-conjugated low-molecular-weight heparin derivative (LHT7): a potent angiogenesis inhibitor.

    PubMed

    Alam, Farzana; Chung, Seung Woo; Hwang, Seung Rim; Kim, Ji-Young; Park, Jooho; Moon, Hyun Tae; Byun, Youngro

    2015-01-01

    In our previous studies, taurocholic acid (TA)-conjugated low-molecular-weight heparin derivative (LHT7) has been proven to be a potent anti-angiogenic agent by demonstrated successful blockage capability of vascular endothelial growth factors (VEGF). Preliminary safety evaluations were conducted based on its mechanism of action and chemical behavior. For this purpose, acute toxicity study, and hematological and serological evaluations were carried out. Additionally, in order to evaluate mechanism-related side effects, both blood pressure and the occurrence of proteinuria were measured using a treatment regime of multiple high doses of LHT7 in a biodistribution study. LD50 values for LHT7 in female and male mice were 56.9 and 64.7 mg kg(-1) doses, respectively. There were no vital fluctuations in the serological and hematological parameters, except for the elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at 100 and 200 mg kg(-1) doses of LHT7, representing vital changes in the liver function. Moreover, the results of mechanism-related studies showed that blood pressure at 50 mg kg(-1) did not change but showed elevated levels of protein in urine. In the biodistribution study, a slight accumulation of LHT7 in the kidney and the liver were observed at the 50 mg kg(-1) repeated dose owing to the presence of bile acid. No fatal damage was observed in this study; most observations were related to the chemical composition or the mechanism of action of the material. PMID:24532548

  7. Granulocytic Myeloid Derived Suppressor Cells Expansion during Active Pulmonary Tuberculosis Is Associated with High Nitric Oxide Plasma Level

    PubMed Central

    El Daker, Sary; Sacchi, Alessandra; Tempestilli, Massimo; Carducci, Claudia; Goletti, Delia; Vanini, Valentina; Colizzi, Vittorio; Lauria, Francesco Nicola; Martini, Federico; Martino, Angelo

    2015-01-01

    Tuberculosis (TB) is still the principal cause of death caused by a single infectious agent, and the balance between the bacillus and host defense mechanisms reflects the different manifestations of the pathology. The aim of this work was to study the role of myeloid-derived suppressor cells (MDSCs) during active pulmonary tuberculosis at the site of infection. We observed an expansion of MDSCs in the lung and blood of patients with active TB, which are correlated with an enhanced amount of nitric oxide in the plasma. We also found that these cells have the remarkable ability to suppress T-cell response, suggesting an important role in the modulation of the immune response against TB. Interestingly, a trend in the diminution of MDSCs was found after an efficacious anti-TB therapy, suggesting that these cells may be used as a potential biomarker for monitoring anti-TB therapy efficacy. PMID:25879532

  8. Application of human stem cell-derived cardiomyocytes in safety pharmacology requires caution beyond hERG.

    PubMed

    Jonsson, Malin K B; Vos, Marc A; Mirams, Gary R; Duker, Göran; Sartipy, Peter; de Boer, Teun P; van Veen, Toon A B

    2012-05-01

    Human embryonic stem cell-derived cardiomyocytes (hESC-CM) have been proposed as a new model for safety pharmacology. So far, a thorough description of their basic electrophysiology and extensive testing, and mechanistic explanations, of their overall pro-arrhythmic ability is lacking. Under standardized conditions, we have evaluated the sensitivity of hESC-CM to proarrhythmic provocations by blockade of hERG and other channels. Using voltage patch clamp, some ion current densities (pA/pF) in hESC-CM were comparable to adult CM: I(Kr) (-12.5 ± 6.9), I(Ks) (0.65 ± 0.12), I(Na,peak) (-72 ± 21), I(Na,late) (-1.10 ± 0.36), and I(Ca,L) (-4.3 ± 0.6). I(f) density was larger (-10 ± 1.1) and I(K1) not existent or very small (-2.67 ± 0.3). The low I(K1) density was corroborated by low KCNJ2 mRNA levels. Effects of pro-arrhythmic compounds on action potential (AP) parameters and provocation of early afterdepolarizations (EADs) revealed that Chromanol293B (100 μmol/l) and Bay K8644 (1 μmol/l) both significantly prolonged APD(90). ATX-II (<1 μmol/l ) and BaCl(2) (10 μmol/l ) had no effect on APD. The only compound that triggered EADs was hERG blocker Cisapride. Computer simulations and AP clamp showed that the immature AP of hESC-CM prevents proper functioning of I(Na)-channels, and result in lower peak/maximal currents of several other channels, compared to the adult situation. Lack of functional I(K1) channels and shifted I(Na) channel activation cause a rather immature electrophysiological phenotype in hESC-CM, and thereby limits the potential of this model to respond accurately to pro-arrhythmic triggers other than hERG block. Maturation of the electrical phenotype is a prerequiste for future implementation of the model in arrhythmogenic safety testing. PMID:22353256

  9. Ellipsometric studies of synthetic albumin-binding chitosan-derivatives and selected blood plasma proteins

    NASA Astrophysics Data System (ADS)

    Sarkar, Sabyasachi

    This dissertation summarizes work on the synthesis of chitosan-derivatives and the development of ellipsometric methods to characterize materials of biological origin. Albumin-binding chitosan-derivatives were synthesized via addition reactions that involve amine groups naturally present in chitosan. These surfaces were shown to have an affinity towards human serum albumin via ELISA, UV spectroscopy and SDS PAGE. Modified surfaces were characterized with IR ellipsometry at various stages of their synthesis using appropriate optical models. It was found that spin cast chitosan films were anisotropic in nature. All optical models used for characterizing chitosan-derivatives were thus anisotropic. Chemical signal dependence on molecular structure and composition was illustrated via IR spectroscopic ellipsometry (IRSE). An anisotropic optical model of an ensemble of Lorentz oscillators were used to approximate material behavior. The presence of acetic acid in spin-cast non-neutralized chitosan samples was thus shown. IRSE application to biomaterials was also demonstrated by performing a step-wise chemical characterizations during synthesis stages. Protein adsorbed from single protein solutions on these modified surfaces was monitored by visible in-situ variable wavelength ellipsometry. Based on adsorption profiles obtained from single protein adsorption onto silicon surfaces, lumped parameter kinetic models were developed. These models were used to fit experimental data of immunoglobulin-G of different concentrations and approximate conformational changes in fibrinogen adsorption. Biomaterial characterization by ellipsometry was further extended to include characterization of individual protein solutions in the IR range. Proteins in an aqueous environment were characterized by attenuated total internal reflection (ATR) IR ellipsometry using a ZnSe prism. Parameterized dielectric functions were created for individual proteins using Lorentz oscillators. These

  10. Granulocytic myeloid-derived suppressor cells inversely correlate with plasma arginine and overall survival in critically ill patients

    PubMed Central

    Gey, A; Tadie, J-M; Caumont-Prim, A; Hauw-Berlemont, C; Cynober, L; Fagon, J-Y; Terme, M; Diehl, J-L; Delclaux, C; Tartour, E

    2015-01-01

    Critically ill patients display a state of immunosuppression that has been attributed in part to decreased plasma arginine concentrations. However, we and other authors have failed to demonstrate a clinical benefit of L-arginine supplementation. We hypothesize that, in these critically ill patients, these low plasma arginine levels may be secondary to the presence of granulocytic myeloid-derived suppressor cells (gMDSC), which express arginase known to convert arginine into nitric oxide (NO) and citrulline. Indeed, in a series of 28 non-surgical critically ill patients, we showed a dramatic increase in gMDSC compared to healthy subjects (P = 0·0002). A significant inverse correlation was observed between arginine levels and gMDSC (P = 0·01). As expected, gMDSC expressed arginase preferentially in these patients. Patients with high gMDSC levels on admission to the medical intensive care unit (MICU) presented an increased risk of death at day 7 after admission (P = 0·02). In contrast, neither plasma arginine levels, monocytic MDSC levels nor neutrophil levels were associated with overall survival at day 7. No relationship was found between body mass index (BMI) or simplified acute physiology score (SAPS) score, sequential organ failure assessment (SOFA) score or gMDSC levels, eliminating a possible bias concerning the direct prognostic role of these cells. As gMDSC exert their immunosuppressive activity via multiple mechanisms [production of prostaglandin E2 (PGE2), interleukin (IL)-10, arginase, etc.], it may be more relevant to target these cells, rather than simply supplementing with L-arginine to improve immunosuppression and its clinical consequences observed in critically ill patients. PMID:25476957

  11. Modulatory effect of coffee fruit extract on plasma levels of brain-derived neurotrophic factor in healthy subjects.

    PubMed

    Reyes-Izquierdo, Tania; Nemzer, Boris; Shu, Cynthia; Huynh, Lan; Argumedo, Ruby; Keller, Robert; Pietrzkowski, Zb

    2013-08-28

    The present single-dose study was performed to assess the effect of whole coffee fruit concentrate powder (WCFC), green coffee caffeine powder (N677), grape seed extract powder (N31) and green coffee bean extract powder (N625) on blood levels of brain-derived neurotrophic factor (BDNF). Randomly assorted groups of fasted subjects consumed a single, 100mg dose of each material. Plasma samples were collected at time zero (T0) and at 30 min intervals afterwards, up to 120 min. A total of two control groups were included: subjects treated with silica dioxide (as placebo) or with no treatment. The collected data revealed that treatments with N31 and N677 increased levels of plasma BDNF by about 31% under these experimental conditions, whereas treatment with WCFC increased it by 143% (n 10), compared with baseline. These results indicate that WCFC could be used for modulation of BDNF-dependent health conditions. However, larger clinical studies are needed to support this possibility. PMID:23312069

  12. Comparison of several insulin sensitivity indices derived from basal plasma insulin and glucose levels with minimal model indices.

    PubMed

    García-Estévez, D A; Araújo-Vilar, D; Fiestras-Janeiro, G; Saavedra-González, A; Cabezas-Cerrato, J

    2003-01-01

    Some techniques for the evaluation of insulin resistance (IR), such as the clamp technique, are not viable for the study of large populations; and for this reason, alternative approaches based on fasting plasma glucose (FPG) and plasma insulin (FPI) have been proposed. The aim of this study was to compare the IR calculations obtained from FPI and FPG values with the insulin sensitivity (IS) index derived from the minimal model. Eighty-seven healthy subjects with a wide range of body mass index (18 - 44 kg x m -2) and 16 DM2 non-obese patients were included in the study. All of the patients underwent a frequently sampled intravenous glucose tolerance test (FSIGTT), and the minimal model of glucose was used for the estimation of insulin sensitivity (IS MINIMAL ). The HOMA-IR index, the Avignon index, and the quotient FPG/FPI were used to calculate basal steady-state IR. The basal IR value that best correlated with IS was Log (1/HOMA-IR) (r = 0.70, p < 0.001). All of the basal indices showed a high correlation with each other. In conclusions, insulin sensitivity indices as determined from the basal glycaemia and insulinemia values are not good estimators for metabolic reality from the perspective of the minimal model. Nevertheless, they might well have an IR screening value for epidemiological studies, as long as there is no pancreatic beta-cell dysfunction. PMID:12669265

  13. Tetramer-organizing polyproline-rich peptides differ in CHO cell-expressed and plasma-derived human butyrylcholinesterase tetramers.

    PubMed

    Schopfer, Lawrence M; Lockridge, Oksana

    2016-06-01

    Tetrameric butyrylcholinesterase (BChE) in human plasma is the product of multiple genes, namely one BCHE gene on chromosome 3q26.1 and multiple genes that encode polyproline-rich peptides. The function of the polyproline-rich peptides is to assemble BChE into tetramers. CHO cells transfected with human BChE cDNA express BChE monomers and dimers, but only low quantities of tetramers. Our goal was to identify the polyproline-rich peptides in CHO-cell derived human BChE tetramers. CHO cell-produced human BChE tetramers were purified from serum-free culture medium. Peptides embedded in the tetramerization domain were released from BChE tetramers by boiling and identified by liquid chromatography-tandem mass spectrometry. A total of 270 proline-rich peptides were sequenced, ranging in size from 6-41 residues. The peptides originated from 60 different proteins that reside in multiple cell compartments including the nucleus, cytoplasm, and endoplasmic reticulum. No single protein was the source of the polyproline-rich peptides in CHO cell-expressed human BChE tetramers. In contrast, 70% of the tetramer-organizing peptides in plasma-derived BChE tetramers originate from lamellipodin. No protein source was identified for polyproline peptides containing up to 41 consecutive proline residues. In conclusion, the use of polyproline-rich peptides as a tetramerization motif is documented only for the cholinesterases, but is expected to serve other tetrameric proteins as well. The CHO cell data suggest that the BChE tetramer-organizing peptide can arise from a variety of proteins. PMID:26947244

  14. Contraints on Solar Wind Plasma Properties Derived from Coordinated Coronal Observations

    NASA Technical Reports Server (NTRS)

    Esser, Ruth; Wagner, William (Technical Monitor)

    2004-01-01

    The goal of the proposed research was to increase the understanding of coronal plasma phenomena by making use of different observational approaches and combine the observations with the necessary theoretical considerations. During the funding period we studied the formation of spectral lines in the corona and transition region. We compared the spectral line ratios that would arise from the type of temperature profile commonly used to explain in situ ion fractions with the actual observed line ratios. We also carried out a theoretical study to investigate how large the electron temperatures can be in the near sun region. We carried out more detailed studies to show that differential flow speeds between ions of the same element can not bridge the above gap between low coronal electron temperatures and high in situ ion fractions. To investigate the drift between core and halo in the electron distribution function, which is observed in situ in the solar wind, we developed the first solar wind model with two electron populations. It was found that the anomalous frictional forces acting on the halo electrons are the dominant factor inhibiting the core-halo drift in the East solar wind. We used kinetic modeling to investigate the Alfvenic turbulence in the extended corona. In these studies we also included the effects of proton heating.

  15. A statistical evaluation of the safety factor and species sensitivity distribution approaches to deriving environmental quality guidelines.

    PubMed

    Zajdlik, Barry Alan

    2016-04-01

    The species sensitivity distribution (SSD) distribution approach to estimating water quality guidelines (WQGs) is the preferred method in all jurisdictions reviewed (Australia, Canada, New Zealand, Organisation for Economic Co-operation and Development [OECD] members, South Africa, United States) and is one of the recommended methods for European Commission members for 33 priority and priority hazardous substances. In the event that jurisdiction-specific criteria for data quality, quantity, and taxonomic representation are not met, all of these jurisdictions endorse the use of additional safety factors (SFs) applied to either the SSD-based WQG or, the lowest suitable toxicity test endpoint. In Canada, the British Columbia Ministry of Environment endorses this latter approach as the preferred approach in the belief that so-derived WQGs are more protective than SSD-based WQGs. The level of protection afforded by the latter SF approach was evaluated by statistically sampling minima from random samples of the following distributions: normal, Gumbel, logistic, and Weibull, using a range of coefficients of variation (cVs) and applying the SFs of 2 or 10 used in British Columbia. The simulations indicate that the potentially affected fraction of species (PAF) can be as high as 20%, or, approach 0%. The PAF varies with sample size and CV. Because CVs can vary systematically with mode of toxic action, the PAF using SF-based WQGs can also vary systematically with analyte class. The varying levels of protection afforded by SF-based WQGs are generally inconsistent with the common water quality management goal that allows for a small degree of change under long-term exposure. The findings suggest that further efforts be made to develop high-quality WQGs that support informed decision making and are consistent with the environmental management goal instead of using SFs in the hope of achieving an acceptable but unknown, degree of environmental protection. PMID:26272692

  16. Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease

    PubMed Central

    Boxer, Adam; Schwartz, Janice B.; Abner, Erin L.; Petersen, Ronald C.; Miller, Bruce L.; Kapogiannis, Dimitrios

    2015-01-01

    Objective: Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy. Methods: Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients with AD (n = 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker. Results: Mean exosomal levels of cathepsin D, lysosome-associated membrane protein 1 (LAMP-1), and ubiquitinylated proteins were significantly higher and of heat-shock protein 70 significantly lower for AD than controls in cross-sectional studies (p ≤ 0.0005). Levels of cathepsin D, LAMP-1, and ubiquitinylated protein also were significantly higher for patients with AD than for patients with frontotemporal dementia (p ≤ 0.006). Step-wise discriminant modeling of the protein levels correctly classified 100% of patients with AD. Exosomal levels of all proteins were similarly significantly different from those of matched controls in 20 patients 1 to 10 years before and at diagnosis of AD (p ≤ 0.0003). Conclusions: Levels of autolysosomal proteins in neurally derived blood exosomes distinguish patients with AD from case controls and appear to reflect the pathology of AD up to 10 years before clinical onset. These preliminary results confirm in living patients with AD the early appearance of neuronal lysosomal dysfunction and suggest that these proteins may be useful biomarkers in large prospective studies. PMID:26062630

  17. Fabrication and physical and biological properties of fibrin gel derived from human plasma

    NASA Astrophysics Data System (ADS)

    Zhao, Haiguang; Ma, Lie; Zhou, Jie; Mao, Zhengwei; Gao, Changyou; Shen, Jiacong

    2008-03-01

    The fast development of tissue engineering and regenerative medicine drives the old biomaterials, for example, fibrin glue, to find new applications in these areas. Aiming at developing a commercially available hydrogel for cell entrapment and delivery, in this study we optimized the fabrication and gelation conditions of fibrin gel. Fibrinogen was isolated from human plasma by a freeze-thaw circle. Gelation of the fibrinogen was accomplished by mixing with thrombin. Absorbance of the fibrinogen/thrombin mixture at 550 nm as a function of reaction time was monitored by UV-VIS spectroscopy. It was found that the clotting time is significantly influenced by the thrombin concentration and the temperature, while less influenced by the fibrinogen concentration. After freeze-drying, the fibrin gel was characterized by scanning electron microscopy (SEM), revealing fibrous microstructure. Thermal gravimetric analysis found that the degradation temperature of the crosslinked fibrin gel starts from 288 °C, which is about 30 °C higher than that of the fibrinogen. The hydrogel has an initial water-uptake ratio of ~50, decreased to 30-40 after incubation in water for 11 h depending on the thrombin concentration. The fibrin gels lost their weights in PBS very rapidly, while slowly in DMEM/fetal bovine serum and DMEM. In vitro cell culture found that human fibroblasts could normally proliferate in the fibrin gel with spreading morphology. In conclusion, the fibrin gel containing higher concentration of fibrinogen (20 mg ml-1) and thrombin (5 U ml-1) has suitable gelation time and handling properties, and thus is applicable as a delivery vehicle for cells such as fibroblasts.

  18. Autologous platelet-rich plasma: a biological supplement to enhance adipose-derived mesenchymal stem cell expansion.

    PubMed

    Atashi, Fatemeh; Jaconi, Marisa E E; Pittet-Cuénod, Brigitte; Modarressi, Ali

    2015-03-01

    Currently the use of non-autologous cell culture media (e.g., animal-derived or allogeneic serum) for clinical applications of mesenchymal stem cells (MSCs) is criticized by regulatory agencies. Autologous platelet-rich plasma (PRP) is proposed as a safer alternative medium supplement for adipose-derived mesenchymal stem cells (AT-MSC) culture. To study its efficiency on cell proliferation, AT-MSCs were cultured for 10 days in media supplemented with different concentrations of autologous non-activated PRP (nPRP) or thrombin-activated PRP (tPRP) (1-60%). AT-MSC proliferation, cell phenotype, multipotency capacity, and chromosome stability were assessed and compared to AT-MSCs expanded in a classical medium supplemented with 10% of fetal bovine serum (FBS). Culture media supplemented with nPRP showed dose-dependent higher AT-MSC proliferation than did FBS or tPRP. Twenty percent nPRP was the most effective concentration to promote cell proliferation. This condition increased 13.9 times greater AT-MSC number in comparison to culture with FBS, without changing the AT-MSC phenotype, differentiation capacity, and chromosome status. We concluded that 20% autologous nPRP is a safe, efficient, and cost-effective supplement for AT-MSC expansion. It should be considered as an alternative to FBS or other nonautologous blood derivatives. It could serve as a potent substitute for the validation of future clinical protocols as it respects good manufacturing practices and regulatory agencies' standards. PMID:25025830

  19. Autologous Platelet-Rich Plasma: A Biological Supplement to Enhance Adipose-Derived Mesenchymal Stem Cell Expansion

    PubMed Central

    Atashi, Fatemeh; Jaconi, Marisa E.E.; Pittet-Cuénod, Brigitte

    2015-01-01

    Currently the use of non-autologous cell culture media (e.g., animal-derived or allogeneic serum) for clinical applications of mesenchymal stem cells (MSCs) is criticized by regulatory agencies. Autologous platelet-rich plasma (PRP) is proposed as a safer alternative medium supplement for adipose-derived mesenchymal stem cells (AT-MSC) culture. To study its efficiency on cell proliferation, AT-MSCs were cultured for 10 days in media supplemented with different concentrations of autologous non-activated PRP (nPRP) or thrombin-activated PRP (tPRP) (1–60%). AT-MSC proliferation, cell phenotype, multipotency capacity, and chromosome stability were assessed and compared to AT-MSCs expanded in a classical medium supplemented with 10% of fetal bovine serum (FBS). Culture media supplemented with nPRP showed dose-dependent higher AT-MSC proliferation than did FBS or tPRP. Twenty percent nPRP was the most effective concentration to promote cell proliferation. This condition increased 13.9 times greater AT-MSC number in comparison to culture with FBS, without changing the AT-MSC phenotype, differentiation capacity, and chromosome status. We concluded that 20% autologous nPRP is a safe, efficient, and cost-effective supplement for AT-MSC expansion. It should be considered as an alternative to FBS or other nonautologous blood derivatives. It could serve as a potent substitute for the validation of future clinical protocols as it respects good manufacturing practices and regulatory agencies' standards. PMID:25025830

  20. A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia

    PubMed Central

    2013-01-01

    Background Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ. The primary objective was to determine the safety of BM- MSCs in patients with CLI. Methods Prospective, double blind randomized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4, III-5, or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment. The primary end point was incidence of treatment – related adverse events (AE). Exploratory efficacy end points were improvement in rest pain, increase in Ankle Brachial Pressure Index (ABPI), ankle pressure, healing of ulcers, and amputation rates. Twenty patients (BM-MSC: Placebo = 1:1) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo (PlasmaLyte A) at the gastrocnemius muscle of the ischemic limb. Results Improvement was observed in the rest pain scores in both the arms. Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group. Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events (SAE) were similar in both the arms (5 in BM-MSC and 4 in the placebo group). SAEs resulted in death, infected gangrene, amputations in these patients. It was observed that the SAEs were related to disease progression and not related to stem cells. Conclusion BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight. Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies. Trial registration NIH website (http

  1. Plasma Level of Placenta-Derived Macrophage-Stimulating Protein -Chain in Preeclampsia before 20 Weeks of Pregnancy

    PubMed Central

    Ma, Qingling; Chen, Ruihua

    2016-01-01

    Object This study aimed to investigate the diagnostic value of placenta-derived macrophage-stimulating protein α-chain (MSP-α) before the 20th week of gestation for the early diagnosis of preeclampsia (PE). Methods and Materials Two parts of this nested case-control study were simultaneously executed, and 1500 pregnant women were recruited. A total of 124 pregnant women were included in the plasma analysis part of this study. The MSP-α plasma level was measured before the 20th week of gestation, and the participants were followed until delivery. A case group of 62 women with PE and a control group of 62 women matched by gestational age, maternal age, and pre-pregnancy BMI (with normotensive pregnancies) were evaluated. In the placenta analysis part of this nested case-control study, the placentas of 34 pregnant women were randomly obtained. The placental levels of MSP were measured in 17 individuals with PE (case group) and in 17 women with a normotensive pregnancy matched by gestational age and maternal age (control group). Results The plasma level of MSP-α was higher in the PE group than in the control group before the 20th week of gestation (p < 0.001). In addition, compared to the women with severe features in the PE group, those without severe features had a significantly higher plasma MSP-α level before the 20th week of gestation (p < 0.001). The area under the receiver operating characteristic curve (AUC) of MSP-α before the 20th week of gestation was 0.905 (95% CI, 0.811–0.962) for the women with early-onset PE without severe features. With regard to the placenta, the PE group (accumulated optical density, IOD [SUM] = 8862.37 ± 2064.42) exhibited increased MSP staining (more intense MSP staining or more extensive staining) compared with the control group (normal pregnancies (IOD [SUM] = 447.92 ± 114.72, P < 0.001). Furthermore, increased MSP staining was detected among the women without severe features compared with those with severe features in

  2. Blood-derived topical therapy for ocular surface diseases.

    PubMed

    Soni, Nishant G; Jeng, Bennie H

    2016-01-01

    Human serum-derived and plasma-derived therapies have become increasingly popular in the treatment of ocular surface disorders, with mounting clinical and scientific evidence suggesting good safety and efficacy profiles. These therapies may be considered for various ocular surface conditions, such as dry eye syndrome and persistent epithelial defect, when conservative management does not suffice. The costly and inconvenient process of obtaining the blood-derived products is the barrier to their more widespread use. Some blood-derived therapies, such as umbilical cord serum-derived and platelet-derived plasma preparations, may be more viable options since these therapies can be made readily available to patients. In this review, the existing literature on the safety and efficacy of blood-derived products, such as autologous serum tears, in the treatment of ocular surface diseases is discussed. Issues relevant to the production of autologous serum tears are also described. PMID:26178904

  3. Allogeneic adipose tissue-derived mesenchymal stem cells in combination with platelet rich plasma are safe and effective in the therapy of superficial digital flexor tendonitis in the horse.

    PubMed

    Ricco, S; Renzi, S; Del Bue, M; Conti, V; Merli, E; Ramoni, R; Lucarelli, E; Gnudi, G; Ferrari, M; Grolli, S

    2013-01-01

    Overstrain tendonitis are common pathologies in the sport horses. Therapeutic approaches to tendon healing do not always result in a satisfactory anatomical and functional repair, and healed tendon is often characterized by functional impairment and high risk of reinjury. Recently, mesenchymal stem cells (MSCs) and platelet rich plasma (PRP) have been proposed as novel therapeutic treatments to improve the tendon repair process. MSCs are multipotent, easy to culture and being originated from adult donors do not pose ethical issues. To date, autologous MSCs have been investigated mainly in the treatment of large bone defects, cardiovascular diseases, osteogenesis imperfecta and orthopaedic injuries both in human and veterinary medicine. The clinical applications in which autologous MSCs can be used are limited because patient-specific tissue collection and cell expansion require time. For clinical applications in which MSCs should be used right away, it would be more practical to use cells collected from a donor, expanded in vitro and banked to be readily available when needed. However, there are concerns over the safety and the efficacy of allogeneic MSCs. The safety and efficacy of a therapy based on the use of allogeneic adipose tissue-derived mesenchymal stem cells (ASCs) associated to platelet rich plasma (PRP) were evaluated in 19 horses affected by acute or subacute overstrain superficial digital flexor tendonitis (SDFT). The application of allogeneic ASCs neither raised clinical sign of acute or chronic adverse tissue reactions, nor the formation of abnormal tissue in the long-term. After a follow-up of 24 months, 89.5% horses returned to their previous level of competition, while the reinjury rate was 10.5%, comparable to those recently reported for SDFT treated with autologous bone marrow derived MSCs. This study suggests that the association between allogeneic ASCs and PRP can be considered a safe and effective strategy for the treatment of SDF tendonitis

  4. The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese heroin-dependent patients

    PubMed Central

    Chen, Shiou-Lan; Lee, Sheng-Yu; Chang, Yun-Hsuan; Wang, Tzu-Yun; Chen, Shih-Heng; Chu, Chun-Hsien; Chen, Po See; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

    2015-01-01

    BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of long-term heroin use. Thus, we investigated the relationships between brain-derived neurotrophic factor (BDNF) plasma concentrations and the BDNF Val66Met nucleotide polymorphism (SNP) in heroin-dependent patients. The pretreatment expression levels of plasma BDNF and the BDNF Val66Met SNP in 172 heroin-dependent patients and 102 healthy controls were checked. BDNF levels were significantly lower in patients (F = 52.28, p < 0.0001), but the distribution of the SNP was not significantly different. Nor were plasma BDNF levels significantly different between Met/Met, Met/Val, and Val/Val carriers in each group, which indicated that the BDNF Val66Met SNP did not affect plasma BDNF levels in our participants. In heroin-dependent patients, plasma BDNF levels were negatively correlated with the length of heroin dependency. Long-term (>15 years) users had significantly lower plasma BDNF levels than did short-term (<5 years) users. We conclude that plasma BDNF concentration in habitual heroin users are not affected by BDNF Val66Met gene variants, but by the length of the heroin dependency. PMID:25640280

  5. The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese heroin-dependent patients.

    PubMed

    Chen, Shiou-Lan; Lee, Sheng-Yu; Chang, Yun-Hsuan; Wang, Tzu-Yun; Chen, Shih-Heng; Chu, Chun-Hsien; Chen, Po See; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

    2015-01-01

    BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of long-term heroin use. Thus, we investigated the relationships between brain-derived neurotrophic factor (BDNF) plasma concentrations and the BDNF Val66Met nucleotide polymorphism (SNP) in heroin-dependent patients. The pretreatment expression levels of plasma BDNF and the BDNF Val66Met SNP in 172 heroin-dependent patients and 102 healthy controls were checked. BDNF levels were significantly lower in patients (F = 52.28, p < 0.0001), but the distribution of the SNP was not significantly different. Nor were plasma BDNF levels significantly different between Met/Met, Met/Val, and Val/Val carriers in each group, which indicated that the BDNF Val66Met SNP did not affect plasma BDNF levels in our participants. In heroin-dependent patients, plasma BDNF levels were negatively correlated with the length of heroin dependency. Long-term (>15 years) users had significantly lower plasma BDNF levels than did short-term (<5 years) users. We conclude that plasma BDNF concentration in habitual heroin users are not affected by BDNF Val66Met gene variants, but by the length of the heroin dependency. PMID:25640280

  6. Effect of autologous platelet-rich plasma on the chondrogenic differentiation of rabbit adipose-derived stem cells in vitro

    PubMed Central

    TANG, XIAO-BO; DONG, PEI-LONG; WANG, JIAN; ZHOU, HAI-YANG; ZHANG, HAI-XIANG; WANG, SHAN-ZHENG

    2015-01-01

    This study aimed to isolate rabbit adipose-derived stem cells (ADSCs) and explore the potential of platelet-rich plasma (PRP) in the chondrogenic differentiation of ADSCs, thereby potentially providing a new approach for the repair and regeneration of cartilage injury. Rabbit ADSCs were isolated and characterized by induction towards adipogenic, osteogenic and chondrogenic lineages in vitro. The isolated ADSCs were also cultured with or without 10% PRP. Immunofluorescence staining, toluidine blue staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect type II collagen (Col II) and aggrecan (AGC) expression. Col II immunofluorescence staining and toluidine blue staining indicated that following induction by autologous PRP, ADSCs manifested Col II and AGC expression. The expression of Col II and AGC mRNA was significantly upregulated in the PRP-treated cells when compared with that in control cells. Autologous PRP produced by laboratory centrifugation was able to promote the chondrogenic differentiation of rabbit ADSCs in vitro. PMID:26622340

  7. Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage

    PubMed Central

    2013-01-01

    Introduction Adipose-derived stem cells (ADSCs) have been isolated, expanded, and applied in the treatment of many diseases. ADSCs have also been used to treat injured articular cartilage. However, there is controversy regarding the treatment efficiency. We considered that ADSC transplantation with activated platelet-rich plasma (PRP) may improve injured articular cartilage compared with that of ADSC transplantation alone. In this study, we determined the role of PRP in ADSC transplantation to improve the treatment efficiency. Methods ADSCs were isolated and expanded from human adipose tissue. PRP was collected and activated from human peripheral blood. The effects of PRP were evaluated in vitro and in ADSC transplantation in vivo. In vitro, the effects of PRP on ADSC proliferation, differentiation into chondrogenic cells, and inhibition of angiogenic factors were investigated at three concentrations of PRP (10%, 15% and 20%). In vivo, ADSCs pretreated with or without PRP were transplanted into murine models of injured articular cartilage. Results PRP promoted ADSC proliferation and differentiation into chondrogenic cells that strongly expressed collagen II, Sox9 and aggrecan. Moreover, PRP inhibited expression of the angiogenic factor vascular endothelial growth factor. As a result, PRP-pretreated ADSCs improved healing of injured articular cartilage in murine models compared with that of untreated ADSCs. Conclusion Pretreatment of ADSCs with PRP is a simple method to efficiently apply ADSCs in cartilage regeneration. This study provides an important step toward the use of autologous ADSCs in the treatment of injured articular cartilage. PMID:23915433

  8. The Effect of Human Platelet-Rich Plasma on Adipose-Derived Stem Cell Proliferation and Osteogenic Differentiation

    PubMed Central

    Tavakolinejad, Sima; Khosravi, Mohsen; Mashkani, Baratali; Ebrahimzadeh Bideskan, Alireza; Sanjar Mossavi, Nasser; Parizadeh, Seyyed Mohammad Reza; Hamidi Alamdari, Daryoush

    2014-01-01

    Background: The cultured mesenchymal stem cells (MSC) have been used in many clinical trials; however, there are still some concerns about the cultural conditions. One concern is related to the use of FBS as a widely used xenogeneic supplement in the culture system. Human platelet-rich plasma (hPRP) is a candidate replacement for FBS. In this study, the effect of hPRP on MSC proliferation and osteogenic differentiation has been evaluated. Methods: Human adipose-derived stem cells (hADSC) were expanded. Cells from the third passage were characterized by flow cytometric analysis and used for in vitro experiments. Resazurin and alizarin red stains were used for cell proliferation and osteogenic differentiation assays, respectively. Results: Treatment with hPRP resulted in a statistically significant increase in cell proliferation compare to the negative control group (P<0.001). Cell proliferation in the 15% hPRP group was also significantly higher than that in the 10% hPRP group (P<0.05). Additionally, it caused less osteogenic differentiation of the hADSC compared to the FBS (P<0.001), but in comparison to negative control, it caused acceptable mineralization (P<0.001). Conclusion: These findings indicate that hPRP not only improves the proliferation but also it can be a suitable substitution in osteogenic differentiation for clinical purposes. However, the clinical application value of hPRP still needs more investigation. PMID:24842141

  9. Characterization of membrane protein interactions in plasma membrane derived vesicles with quantitative imaging Förster resonance energy transfer.

    PubMed

    Sarabipour, Sarvenaz; Del Piccolo, Nuala; Hristova, Kalina

    2015-08-18

    Here we describe an experimental tool, termed quantitative imaging Förster resonance energy transfer (QI-FRET), that enables the quantitative characterization of membrane protein interactions. The QI-FRET methodology allows us to acquire binding curves and calculate association constants for complex membrane proteins in the native plasma membrane environment. The method utilizes FRET detection, and thus requires that the proteins of interest are labeled with florescent proteins, either FRET donors or FRET acceptors. Since plasma membranes of cells have complex topologies precluding the acquisition of two-dimensional binding curves, the FRET measurements are performed in plasma membrane derived vesicles that bud off cells as a result of chemical or osmotic stress. The results overviewed here are acquired in vesicles produced with an osmotic vesiculation buffer developed in our laboratory, which does not utilize harsh chemicals. The concentrations of the donor-labeled and the acceptor-labeled proteins are determined, along with the FRET efficiencies, in each vesicle. The experiments utilize transient transfection, such that a wide variety of concentrations is sampled. Then, data from hundreds of vesicles are combined to yield dimerization curves. Here we discuss recent findings about the dimerization of receptor tyrosine kinases (RTKs), membrane proteins that control cell growth and differentiation via lateral dimerization in the plasma membrane. We focus on the dimerization of fibroblast growth factor receptor 3 (FGFR3), a RTK that plays a critically important role in skeletal development. We study the role of different FGFR3 domains in FGFR3 dimerization in the absence of ligand, and we show that FGFR3 extracellular domains inhibit unliganded dimerization, while contacts between the juxtamembrane domains, which connect the transmembrane domains to the kinase domains, stabilize the unliganded FGFR3 dimers. Since FGFR3 has been documented to harbor many pathogenic

  10. Plasma-derived Extracellular Vesicles Contain Predictive Biomarkers and Potential Therapeutic Targets for Myocardial Ischemic (MI) Injury.

    PubMed

    Cheow, Esther Sok Hwee; Cheng, Woo Chin; Lee, Chuen Neng; de Kleijn, Dominique; Sorokin, Vitaly; Sze, Siu Kwan

    2016-08-01

    Myocardial infarction (MI) triggers a potent inflammatory response via the release of circulatory mediators, including extracellular vesicles (EVs) by damaged cardiac cells, necessary for myocardial healing. Timely repression of inflammatory response are critical to prevent and minimize cardiac tissue injuries, nonetheless, progression in this aspect remains challenging. The ability of EVs to trigger a functional response upon delivery of carried bioactive cargos, have made them clinically attractive diagnostic biomarkers and vectors for therapeutic interventions. Using label-free quantitative proteomics approach, we compared the protein cargo of plasma EVs between patients with MI and from patients with stable angina (NMI). We report, for the first time, the proteomics profiling on 252 EV proteins that were modulated with >1.2-fold after MI. We identified six up-regulated biomarkers with potential for clinical applications; these reflected post-infarct pathways of complement activation (Complement C1q subcomponent subunit A (C1QA), 3.23-fold change, p = 0.012; Complement C5 (C5), 1.27-fold change, p = 0.087), lipoprotein metabolism (Apoliporotein D (APOD), 1.86-fold change, p = 0.033; Apolipoprotein C-III (APOCC3), 2.63-fold change, p = 0.029) and platelet activation (Platelet glycoprotein Ib alpha chain (GP1BA), 9.18-fold change, p < 0.0001; Platelet basic protein (PPBP), 4.72-fold change, p = 0.027). The data have been deposited to the ProteomeXchange with identifier PXD002950. This novel biomarker panel was validated in 43 patients using antibody-based assays (C1QA (p = 0.005); C5 (p = 0.0047), APOD (p = 0.0267); APOC3 (p = 0.0064); GP1BA (p = 0.0031); PPBP (p = 0.0465)). We further present that EV-derived fibrinogen components were paradoxically down-regulated in MI, suggesting that a compensatory mechanism may suppress post-infarct coagulation pathways, indicating potential for therapeutic targeting of this mechanism in MI. Taken together, these data

  11. Application of pentafluorophenyl hydrazine derivatives to the analysis of nabumetone and testosterone in human plasma by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

    PubMed

    Sheen, J F; Her, G R

    2004-12-01

    Two carbonyl compounds, nabumetone and testosterone, were derivatized with pentafluorophenyl hydrazine (PFPH) and analyzed by atmospheric-pressure chemical-ionization mass spectrometry. The PFPH derivatives underwent dissociative electron capture in negative-ion APCI (ECAPCI) and gave intense [M-20](-) ions in the mass spectra. In positive-ion APCI, the PFPH derivatives underwent efficient protonation and gave intense [M + H](+) ions in the mass spectra. In CID, the major product ions of the [M-20](-) ions in ECAPCI corresponded to the partial moiety of PFPH. In contrast, the major product ions of [M + H](+) corresponded to the partial moiety of the analyte. By using selected reaction monitoring (SRM) detection, low pg of nabumetone (1 pg) and testosterone (7 pg) could be detected in both ECAPCI and positive-ion APCI. In comparison with the detection limits (SRM) of the underivatized analytes, use of the PFPH derivatives resulted in 2500-fold and 35-fold sensitivity enhancements for nabumetone and testosterone, respectively. The PFPH derivatives were applied to the analysis of nabumetone and testosterone in human plasma by both ECAPCI and positive-ion APCI and were found to enable detection of 0.1 ng mL(-1) nabumetone in spiked plasma. For testosterone, endogenous testosterone in female plasma was detected in both ECAPCI and positive-ion APCI. PMID:15700167

  12. Physics-based control-oriented modeling and robust feedback control of the plasma safety factor profile and stored energy dynamics in ITER

    NASA Astrophysics Data System (ADS)

    Barton, Justin E.; Besseghir, Karim; Lister, Jo; Schuster, Eugenio

    2015-11-01

    Many challenging plasma control problems still need to be addressed in order for the ITER plasma control system (PCS) to be able to maintain the plasma within a predefined operational space and optimize the plasma state evolution in the tokamak, which will greatly aid in the successful achievement of ITER’s goals. Firstly in this work, a general control-oriented, physics-based modeling approach is developed to obtain first-principles-driven (FPD) models of the plasma magnetic profile and stored energy evolutions valid for high performance, high confinement (H-mode) scenarios, with the goal of developing model-based closed-loop algorithms to control the safety factor profile (q profile) and stored energy evolutions in the tokamak. The FPD model is tailored to H-mode burning plasma scenarios in ITER by employing the DINA-CH & CRONOS free-boundary tokamak simulation code, and the FPD model’s prediction capabilities are demonstrated by comparing the prediction to data obtained from DINA-CH & CRONOS. Secondly, a model-based feedback control algorithm is designed to simultaneously track target q profile and stored energy evolutions in H-mode burning plasma scenarios in ITER by embedding the developed FPD model of the magnetic profile evolution into the control design process. The feedback controller is designed to ensure that the closed-loop system is robust to uncertainties in the electron density, electron temperature and plasma resistivity, and is tested in simulations with the developed FPD model. The effectiveness of the controller is demonstrated by first tracking nominal q profile and stored energy target evolutions, and then modulating the generated fusion power while maintaining the q profile in a stationary condition. In the process, many key practical issues for plasma profile control in ITER are investigated, which will be useful for the development of the ITER PCS that has recently been initiated. Some of the more pertinent investigated issues are the

  13. Derivation of improved load transformation matrices for launchers-spacecraft coupled analysis, and direct computation of margins of safety

    NASA Technical Reports Server (NTRS)

    Klein, M.; Reynolds, J.; Ricks, E.

    1989-01-01

    Load and stress recovery from transient dynamic studies are improved upon using an extended acceleration vector in the modal acceleration technique applied to structural analysis. Extension of the normal LTM (load transformation matrices) stress recovery to automatically compute margins of safety is presented with an application to the Hubble space telescope.

  14. Intervertebral disc regeneration using platelet-rich plasma-containing bone marrow-derived mesenchymal stem cells: A preliminary investigation

    PubMed Central

    WANG, SHAN-ZHENG; JIN, JI-YANG; GUO, YU-DONG; MA, LIANG-YU; CHANG, QING; PENG, XIN-GUI; GUO, FANG-FANG; ZHANG, HAI-XIANG; HU, XIN-FENG; WANG, CHEN

    2016-01-01

    Platelet-rich plasma (PRP) is a promising strategy for intervertebral disc degeneration (IDD). However, the short half-life of growth factors released from PRP cannot continuously stimulate the degenerated discs. Thus, the present study hypothesized that the combined use of PRP and bone marrow-derived mesenchymal stem cells (BMSCs) may repair the early degenerated discs in the long term for their synergistic reparative effect. In the present study, following the induction of early IDD by annular puncture in rabbits, PRP was prepared and mixed with BMSCs (PRP-BMSC group) for injection into the early degenerated discs. As controls, phosphate-buffered saline (PBS; PBS group) and PRP (PRP group) were similarly injected. Rabbits without any intervention served as a control group. At 8 weeks following treatment, histological changes of the injected discs were assessed. Magnetic resonance imaging (MRI) was used to detect the T2-weighted signal intensity of the targeted discs at weeks 1, 2 and 8 following treatment. Annular puncture resulted in disc narrowing and decreased T2-weighted signal intensity. At weeks 1 and 3, MRI examinations showed regenerative changes in the PRP-BMSC group and PRP group, whereas the PBS group exhibited a continuous degenerative process of the discs. At 8 weeks post-injection, the PRP-BMSCs induced a statistically significant restoration of discs, as shown by MRI (PRP-BMSCs, vs.PRP and PBS; P<0.05), which was also confirmed by histological evaluations. Thus, compared with PRP, the administration of PRP-containing BMSCs resulted in a superior regenerative effect on the early degenerated discs, which may be a promising therapeutic strategy for the restoration of early degenerated discs. PMID:26956080

  15. Determination of l-arginine and NG, NG - and NG, NG' -dimethyl-L-arginine in plasma by liquid chromatography as AccQ-Fluor fluorescent derivatives.

    PubMed

    Heresztyn, Tamila; Worthley, Matthew I; Horowitz, John D

    2004-06-15

    A new HPLC assay for the detection of L-arginine, NG, NG-dimethyl-L-arginine (ADMA) and NG, NG' -dimethyl-L-arginine (SDMA) in plasma using the derivatisation reagent AccQ-Fluor (6-aminoquinolyl-N-hydroxysuccinimidyl carbamate) is described. The fluorescent derivatives produced are extremely stable enabling routine processing of large numbers of samples. Arginine and its metabolites are extracted from plasma on strong cation exchange (SCX) cartridges with NG-monomethyl-L-arginine (NMMA) as internal standard, derivatised and separated on a C18 column with acetonitrile in 0.1M sodium acetate buffer pH 6. Separation of the stereoisomers ADMA and SDMA was excellent and improvements to the solid phase extraction (SPE) procedure enabled good recovery (>80%) of arginine, ADMA and SDMA. The utility of the method is exemplified by comparison of plasma concentrations of ADMA, SDMA and arginine in healthy volunteers and diabetic/ischaemic patients. PMID:15135108

  16. The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema

    PubMed Central

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette; Rasmussen, Eva Rye

    2016-01-01

    Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema (ACEi-AE) of the hypopharynx that completely resolved rapidly after the infusion of plasma-derived C1-inhibitor concentrate adding to the sparse reports in the existing literature. PMID:27123347

  17. The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema.

    PubMed

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette; Rasmussen, Eva Rye

    2016-01-01

    Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema (ACEi-AE) of the hypopharynx that completely resolved rapidly after the infusion of plasma-derived C1-inhibitor concentrate adding to the sparse reports in the existing literature. PMID:27123347

  18. Optimized Preparation Method of Platelet-Concentrated Plasma and Noncoagulating Platelet-Derived Factor Concentrates: Maximization of Platelet Concentration and Removal of Fibrinogen

    PubMed Central

    Araki, Jun; Jona, Masahiro; Eto, Hitomi; Aoi, Noriyuki; Kato, Harunosuke; Suga, Hirotaka; Doi, Kentaro; Yatomi, Yutaka

    2012-01-01

    Abstract Platelet-rich plasma (PRP) has been clinically used as an easily prepared growth factor cocktail that can promote wound healing, angiogenesis, and tissue remodeling. However, the therapeutic effects of PRP are still controversial, due partly to the lack of optimized and standardized preparation protocols. We used whole blood (WB) samples to optimize the preparation protocols for PRP, white blood cell-containing (W-PRP), platelet-concentrated plasma (PCP), and noncoagulating platelet-derived factor concentrate (PFC). PRP and W-PRP were most efficiently collected by 10 min centrifugation in a 15-mL conical tube at 230–270 g and 70 g, respectively. To prepare PCP, platelets were precipitated by centrifugation of PRP at >2300 g, 90% of supernatant plasma was removed, and the platelets were resuspended. For preparation of noncoagulating PFC, the supernatant was replaced with one-tenth volume of saline, followed by platelet activation with thrombin. Platelet (before activation) and platelet-derived growth factor (PDGF)-BB (after activation) concentrations in PCP were approximately 20 times greater than those in WB, whereas PFC contained a 20-times greater concentration of platelets before platelet activation and a 50-times greater concentration of PDGF-BB without formation of a fibrin gel after platelet activation than WB. Surprisingly, total PDGF-BB content in the PFC was twice that of activated WB, which suggested that a substantial portion of the PDGF-BB became trapped in the fibrin glue, and replacement of plasma with saline is crucial for maximization of platelet-derived factors. As an anticoagulant, ethylene di-amine tetra-acetic acid disodium inhibited platelet aggregation more efficiently than acid citrate dextrose solution, resulting in higher nonaggregated platelet yield and final PDGF-BB content. These results increase our understanding of how to optimize and standardize preparation of platelet-derived factors at maximum concentrations. PMID

  19. Comparison of electrophysiological data from human-induced pluripotent stem cell-derived cardiomyocytes to functional preclinical safety assays.

    PubMed

    Harris, Kate; Aylott, Mike; Cui, Yi; Louttit, James B; McMahon, Nicholas C; Sridhar, Arun

    2013-08-01

    Human-induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) are a potential source to develop assays for predictive electrophysiological safety screening. Published studies show that the relevant physiology and pharmacology exist but does not show the translation between stem cell cardiomyocyte assays and other preclinical safety screening assays, which is crucial for drug discovery and safety scientists and the regulators. Our studies are the first to show the pharmacology of ion channel blockade and compare them with existing functional cardiac electrophysiology studies. Ten compounds (a mixture of pure hERG [E-4031 and Cisapride], hERG and sodium [Flecainide, Mexiletine, Quinidine, and Terfenadine], calcium channel blockers [Nifedipine and Verapamil], and two proprietary compounds [GSK A and B]) were tested, and results from hiPSC-CMs studied on multielectrode arrays (MEA) were compared with other preclincial models and clinical drug concentrations and effects using integrated risk assessment plots. All ion channel blockers produced (1) functional effects on repolarization and depolarization around the IC25 and IC50 values and (2) excessive blockade of hERG and/or blockade of sodium current precipitated arrhythmias. Our MEA data show that hiPSC-CMs demonstrate relevant pharmacology and show excellent correlations to current functional cardiac electrophysiological studies. Based on these results, MEA assays using iPSC-CMs offer a reliable, cost effective, and surrogate to preclinical in vitro testing, in addition to the 3Rs (refine, reduce, and replace animals in research) benefit. PMID:23690542

  20. Circulating intestine-derived exosomal miR-328 in plasma, a possible biomarker for estimating BCRP function in the human intestines.

    PubMed

    Gotanda, Keisuke; Hirota, Takeshi; Saito, Jumpei; Fukae, Masato; Egashira, Yu; Izumi, Noritomo; Deguchi, Mariko; Kimura, Miyuki; Matsuki, Shunji; Irie, Shin; Ieiri, Ichiro

    2016-01-01

    A variant in the breast cancer resistance protein (BCRP) gene, 421C> A is a useful biomarker for describing large inter-individual differences in the pharmacokinetics of sulfasalazine (SASP), a BCRP substrate. However, large intra-genotypic variability still exists in spite of the incorporation of this variant into the pharmacokinetics of SASP. Since miR-328 negatively regulates BCRP expression in human tissues, we hypothesized that exosomal miR-328 in plasma, which leaks from the intestines, is a possible biomarker for estimating BCRP activity in the human intestines. We established an immunoprecipitation-based quantitative method for circulating intestine-derived miR-328 in plasma using an anti-glycoprotein A33 antibody. A clinical study was conducted with an open-label, non-randomized, and single-arm design involving 33 healthy participants. Intestine-derived exosomal miR-328 levels positively correlated (P < 0.05) with SASP AUC0-48, suggesting that subjects with high miR-328 levels have low intestinal BCRP activity, resulting in the high AUC of SASP. Circulating intestine-derived exosomal miR-328 in plasma has potential as a possible biomarker for estimating BCRP function in the human intestines. PMID:27571936

  1. Circulating intestine-derived exosomal miR-328 in plasma, a possible biomarker for estimating BCRP function in the human intestines

    PubMed Central

    Gotanda, Keisuke; Hirota, Takeshi; Saito, Jumpei; Fukae, Masato; Egashira, Yu; Izumi, Noritomo; Deguchi, Mariko; Kimura, Miyuki; Matsuki, Shunji; Irie, Shin; Ieiri, Ichiro

    2016-01-01

    A variant in the breast cancer resistance protein (BCRP) gene, 421C> A is a useful biomarker for describing large inter-individual differences in the pharmacokinetics of sulfasalazine (SASP), a BCRP substrate. However, large intra-genotypic variability still exists in spite of the incorporation of this variant into the pharmacokinetics of SASP. Since miR-328 negatively regulates BCRP expression in human tissues, we hypothesized that exosomal miR-328 in plasma, which leaks from the intestines, is a possible biomarker for estimating BCRP activity in the human intestines. We established an immunoprecipitation-based quantitative method for circulating intestine-derived miR-328 in plasma using an anti-glycoprotein A33 antibody. A clinical study was conducted with an open-label, non-randomized, and single-arm design involving 33 healthy participants. Intestine-derived exosomal miR-328 levels positively correlated (P < 0.05) with SASP AUC0-48, suggesting that subjects with high miR-328 levels have low intestinal BCRP activity, resulting in the high AUC of SASP. Circulating intestine-derived exosomal miR-328 in plasma has potential as a possible biomarker for estimating BCRP function in the human intestines. PMID:27571936

  2. Plasma Brain-Derived Neurotrophic Factor as a Biomarker for the Main Types of Mild Neurocognitive Disorders and Treatment Efficacy: A Preliminary Study.

    PubMed

    Levada, Oleg A; Cherednichenko, Nataliya V; Trailin, Andriy V; Troyan, Alexandra S

    2016-01-01

    Decreased levels of brain-derived neurotrophic factor (BDNF) are assumed to play a crucial role in the pathophysiology of mild neurocognitive disorders (MNCDs). In this study, we compared plasma BDNF levels (at baseline and after two months of treatment with escitalopram) in patients with the main types of MNCDs and normal controls. 21 patients met the DSM-5 diagnostic criteria for possible MNCD due to Alzheimer's disease (MNCD-AD); 22 patients fulfilled the diagnostic criteria for subcortical vascular MNCD (ScVMNCD) according to Frisoni et al. (2002) and neuroimaging-supported probable diagnosis of vascular MNCD according to DSM-5; 16 subjects entered control group. At baseline, we detected lower BDNF levels in both MNCD groups, which was significant only in subjects with MNCD-AD. Moreover, plasma BDNF level of 21160 pg/mL showed high sensitivity (94%) to discriminate patients with MNCD-AD. Decreased plasma BDNF highly correlated with the severity of memory impairment and total MMSE score in MNCD-AD group. Escitalopram treatment in patients with MNCD-AD or ScVMNCD led to an increase of plasma BDNF concentrations and as a result to a decrease of cognitive, depressive, and anxiety symptom severity. In conclusion, plasma BDNF might be a reliable biomarker for the validation of MNCD-AD diagnosis and treatment efficacy. PMID:27597800

  3. Plasma Brain-Derived Neurotrophic Factor as a Biomarker for the Main Types of Mild Neurocognitive Disorders and Treatment Efficacy: A Preliminary Study

    PubMed Central

    2016-01-01

    Decreased levels of brain-derived neurotrophic factor (BDNF) are assumed to play a crucial role in the pathophysiology of mild neurocognitive disorders (MNCDs). In this study, we compared plasma BDNF levels (at baseline and after two months of treatment with escitalopram) in patients with the main types of MNCDs and normal controls. 21 patients met the DSM-5 diagnostic criteria for possible MNCD due to Alzheimer's disease (MNCD-AD); 22 patients fulfilled the diagnostic criteria for subcortical vascular MNCD (ScVMNCD) according to Frisoni et al. (2002) and neuroimaging-supported probable diagnosis of vascular MNCD according to DSM-5; 16 subjects entered control group. At baseline, we detected lower BDNF levels in both MNCD groups, which was significant only in subjects with MNCD-AD. Moreover, plasma BDNF level of 21160 pg/mL showed high sensitivity (94%) to discriminate patients with MNCD-AD. Decreased plasma BDNF highly correlated with the severity of memory impairment and total MMSE score in MNCD-AD group. Escitalopram treatment in patients with MNCD-AD or ScVMNCD led to an increase of plasma BDNF concentrations and as a result to a decrease of cognitive, depressive, and anxiety symptom severity. In conclusion, plasma BDNF might be a reliable biomarker for the validation of MNCD-AD diagnosis and treatment efficacy. PMID:27597800

  4. Effects of Prolastin C (Plasma-Derived Alpha-1 Antitrypsin) on the acute inflammatory response in patients with ST-segment elevation myocardial infarction (from the VCU-alpha 1-RT pilot study).

    PubMed

    Abbate, Antonio; Van Tassell, Benjamin Wallace; Christopher, Sanah; Abouzaki, Nayef Antar; Sonnino, Chiara; Oddi, Claudia; Carbone, Salvatore; Melchior, Ryan David; Gambill, Michael Lucas; Roberts, Charlotte Susan; Kontos, Michael Christopher; Peberdy, Mary Ann; Toldo, Stefano; Vetrovec, George Wayne; Biondi-Zoccai, Giuseppe; Dinarello, Charles Anthony

    2015-01-01

    Alpha-1 antitrypsin (AAT) has broad anti-inflammatory and immunomodulating properties in addition to inhibiting serine proteases. Administration of human plasma-derived AAT is protective in models of acute myocardial infarction in mice. The objective of this study was to determine the safety and tolerability of human plasma-derived AAT and its effects on the acute inflammatory response in non-AAT deficient patients with ST-segment elevation myocardial infarction (STEMI). Ten patients with acute STEMI were enrolled in an open-label, single-arm treatment study of AAT at 60 mg/kg infused intravenously within 12 hours of admission and following standard of care treatment. C-reactive protein (CRP) and plasma AAT levels were determined at admission, 72 hours, and 14 days, and patients were followed clinically for 12 weeks for the occurrence of new onset heart failure, recurrent myocardial infarction, or death. Twenty patients with STEMI enrolled in previous randomized trials with identical inclusion and/or exclusion criteria, but who received placebo, served as historical controls. Prolastin C was well tolerated and there were no in-hospital adverse events. Compared with historical controls, the area under the curve of CRP levels was significantly lower 14 days after admission in the Prolastin C group (75.9 [31.4 to 147.8] vs 205.6 [78.8 to 410.9] mg/l, p = 0.048), primarily due to a significant blunting of the increase occurring between admission and 72 hours (delta CRP +1.7 [0.2 to 9.4] vs +21.1 [3.1 to 38.0] mg/l, p = 0.007). Plasma AAT levels increased from admission (149 [116 to 189]) to 203 ([185 to 225] mg/dl) to 72 hours (p = 0.005). In conclusion, a single administration of Prolastin C in patients with STEMI is well tolerated and is associated with a blunted acute inflammatory response. PMID:25456867

  5. Platelet-Rich Plasma Promotes the Proliferation of Human Muscle Derived Progenitor Cells and Maintains Their Stemness

    PubMed Central

    Li, Hongshuai; Usas, Arvydas; Poddar, Minakshi; Chen, Chien-Wen; Thompson, Seth; Ahani, Bahar; Cummins, James; Lavasani, Mitra; Huard, Johnny

    2013-01-01

    Human muscle-derived progenitor cells (hMDPCs) offer great promise for muscle cell-based regenerative medicine; however, prolonged ex-vivo expansion using animal sera is necessary to acquire sufficient cells for transplantation. Due to the risks associated with the use of animal sera, the development of a strategy for the ex vivo expansion of hMDPCs is required. The purpose of this study was to investigate the efficacy of using platelet-rich plasma (PRP) for the ex-vivo expansion of hMDPCs. Pre-plated MDPCs, myoendothelial cells, and pericytes are three populations of hMDPCs that we isolated by the modified pre-plate technique and Fluorescence Activated Cell Sorting (FACS), respectively. Pooled allogeneic human PRP was obtained from a local blood bank, and the effect that thrombin-activated PRP-releasate supplemented media had on the ex-vivo expansion of the hMDPCs was tested against FBS supplemented media, both in vitro and in vivo. PRP significantly enhanced short and long-term cell proliferation, with or without FBS supplementation. Antibody-neutralization of PDGF significantly blocked the mitogenic/proliferative effects that PRP had on the hMDPCs. A more stable and sustained expression of markers associated with stemness, and a decreased expression of lineage specific markers was observed in the PRP-expanded cells when compared with the FBS-expanded cells. The in vitro osteogenic, chondrogenic, and myogenic differentiation capacities of the hMDPCs were not altered when expanded in media supplemented with PRP. All populations of hMDPCs that were expanded in PRP supplemented media retained their ability to regenerate myofibers in vivo. Our data demonstrated that PRP promoted the proliferation and maintained the multi-differentiation capacities of the hMDPCs during ex-vivo expansion by maintaining the cells in an undifferentiated state. Moreover, PDGF appears to be a key contributing factor to the beneficial effect that PRP has on the proliferation of hMDPCs. PMID

  6. Possible Role of Plasma Ceruloplasmin and Erythrocyte Sedimentation Rate in Assessing Compliance with Occupational Hygiene and Safety Practices in Waste Management Workers

    PubMed Central

    Odewabi, Adesina O.; Ogundahunsi, Omobola A.; Odewabi, Adenike A.; Oritogun, Kolawole S.; Ekor, Martins

    2013-01-01

    Objectives: Work-related health and safety risks are common among waste management workers (WMWs). This study investigated the level of compliance with safety measures in relation to levels of inflammatory markers among WMWs in Sagamu, South-West Nigeria. Materials and Methods: WMWs comprising 30 cart pushers (CPs) and 50 truck users (TUs) were recruited alongside 45 people from the normal population as control. Data on health complaints were obtained from questionnaire surveys. Inflammation was assessed by measuring plasma ceruloplasmin (Cp), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and albumin. Results: WMWs exhibited a significantly higher prevalence of respiratory and gastrointestinal symptoms and poor compliance with health and safety measures. Significant (P < 0.001) differences were observed in the use of masks, hand gloves, protective clothing, and footwear between TUs and CPs. ESR, Cp, and CRP increased significantly (P < 0.001) by 145, 28.7, and 42.5% in TUs and by 164, 50.5, and 74.3% in CPs, respectively, relative to control. Negative correlation was observed between use of mask (r = -0.225, P < 0.01), use of gloves (r = -0.184, P < 0.05), and Cp and between ESR and washing of hands with soap (r = -0.185, P < 0.05). The use of goggles (r = +0.285, P < 0.001), washing of hands with soap (r = +0.203; P < 0.01), use of masks (r = +0.317, P < 0.001), and use of gloves correlated positively in WMWs. Conclusions: A higher prevalence of work-related symptoms and elevated inflammatory markers in WMWs was related to poor compliance with safety measures. ESR and Cp may be useful predictors of occupational hygiene and compliance with safety measures among Nigerian WMWs. PMID:24082508

  7. Comparison of efficacy, safety and brain derived neurotrophic factor (BDNF) levels in patients of major depressive disorder, treated with fluoxetine and desvenlafaxine.

    PubMed

    Ghosh, R; Gupta, R; Bhatia, M S; Tripathi, A K; Gupta, L K

    2015-12-01

    This randomized, open label, prospective, observational study compared clinical efficacy, safety alongwith plasma BDNF levels in outpatients of depression treated with fluoxetine and desvenlafaxine. Patients (aged 18-60 years) with moderate to severe major depressive disorder (MDD) diagnosed by DSM-IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score ≥14, who were prescribed fluoxetine or desvenlafaxine were included (n=30 in each group). Patients were followed up for 12 weeks for evaluation of clinical efficacy, safety along with BDNF levels. In the fluoxetine group, HAM-D scores at the start of treatment was 19±4.09 which significantly (p<0.05) reduced to 9.24±3.98 at 12 weeks. In the desvenlafaxine group, HAM-D scores at the start of treatment was 18±3.75 which significantly (p<0.05) reduced to 10±3.75 at 12 weeks. The BDNF levels in the fluoxetine group were 775.32±30.38pg/ml at the start of treatment which significantly (p<0.05) increased to 850.3±24.92pg/ml at 12 weeks. The BDNF levels in the desvenlafaxine group were 760.5±28.53pg/ml at the start of treatment which significantly (p<0.05) increased to 845.8±32.82pg/ml at 12 weeks. Both the antidepressants were found to be safe and well tolerated. The efficacy and the safety profile of desvenlafaxine is comparable to fluoxetine in patients of MDD. BDNF levels were significantly increased post-treatment with both the antidepressive agents. Whether BDNF may have a prognostic value in predicting treatment response to antidepressant drugs needs to be investigated in a larger patient population. PMID:26514447

  8. Analysis of methyloxime derivatives of intact esters of testosterone and boldenone in equine plasma using ultra high performance liquid chromatography tandem mass spectrometry.

    PubMed

    Gray, Bobby P; Teale, Phil; Pearce, Clive M

    2011-04-01

    Analysis of equine plasma samples to detect the abuse of anabolic steroids can be complicated when the parent steroid is endogenous to the animal. Anabolic steroids are usually administered intramuscularly as synthetic esters and therefore detection of the exogenous esters provides unequivocal proof of illegal administration. An ultra high performance liquid chromatography tandem mass spectrometric (UPLC-MSMS) method for the analysis of esters of testosterone (propionate, phenylpropionate, isocaproate, and decanoate) and boldenone (undecylenate) in equine plasma has been developed. Esters were extracted from equine plasma using a mixture of hexane and ethyl acetate and treated with methoxyamine hydrochloride to form methyloxime derivatives. Metenolone enanthate was used as an internal standard. After chromatographic separation, the derivatized steroid esters were quantified using selected reaction monitoring (SRM). The limit of detection for all of the steroid esters, based on a signal to noise ratio (S/N) of 3:1, was 1-3 pg/mL. The lower limit of quantification (LLOQ) for the all of the steroid esters was 5 pg/mL when 2 mL of plasma was extracted. Recovery of the steroid esters was 85-97% for all esters except for testosterone decanoate which was recovered at 62%. The intra-day coefficient of variation (CV) for the analysis of plasma quality control (QC) samples was less than 9.2% at 40 pg/mL and less than 6.0% at 400 pg/mL. The developed assay was used to successfully confirm the presence of intact testosterone esters in equine plasma samples following intramuscular injection of Durateston® (mixed testosterone esters). PMID:21287693

  9. Departures from local thermodynamic equilibrium in cutting arc plasmas derived from electron and gas density measurements using a two-wavelength quantitative Schlieren technique

    SciTech Connect

    Prevosto, L.; Mancinelli, B.; Artana, G.; Kelly, H.

    2011-03-15

    A two-wavelength quantitative Schlieren technique that allows inferring the electron and gas densities of axisymmetric arc plasmas without imposing any assumption regarding statistical equilibrium models is reported. This technique was applied to the study of local thermodynamic equilibrium (LTE) departures within the core of a 30 A high-energy density cutting arc. In order to derive the electron and heavy particle temperatures from the inferred density profiles, a generalized two-temperature Saha equation together with the plasma equation of state and the quasineutrality condition were employed. Factors such as arc fluctuations that influence the accuracy of the measurements and the validity of the assumptions used to derive the plasma species temperature were considered. Significant deviations from chemical equilibrium as well as kinetic equilibrium were found at elevated electron temperatures and gas densities toward the arc core edge. An electron temperature profile nearly constant through the arc core with a value of about 14000-15000 K, well decoupled from the heavy particle temperature of about 1500 K at the arc core edge, was inferred.

  10. Improved performance by plasma-treated silicate phosphor particles with a sol-gel derived protective coating of indium oxide

    NASA Astrophysics Data System (ADS)

    Kim, Hyeon; Yun, Changhun; Jeon, Sie Wook; Lee, June Key; Kim, Jae Pil

    2016-03-01

    The optical properties and reliability of silicate phosphor was fairly improved by an amorphous In2O3 protective coating on plasma-treated phosphor particles. The In2O3 layers were coated using a conventional sol-gel method with alkoxide precursor in N2 gas. The surface morphology of silicate particles was smoother after Ar-plasma surface modification. When plasma surface treatment of the phosphor was applied before sol-gel coating, the In2O3 coating was almost 3-times thicker, and the surface of the phosphor particles was smoother, than could be obtained when sol-gel coating was not preceded by plasma treatment. This was because the treatment caused the surface to become hydrophilic. The light absorption rate and quantum efficiency were increased from 75.3% and 93.8%, to 79.2% and 95.7%, after plasma-treated In2O3 coating. Bare silicate phosphor used in 450-nm vertical-type LEDs, displayed 10% decreased optical output, whereas In2O3-coated phosphor showed just 3% decreased optical output after 1000 h of input current at 350 mA; under conditions of high humidity and high temperature.

  11. Identification of Plasma and Urinary Metabolites and Catabolites Derived from Orange Juice (Poly)phenols: Analysis by High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry.

    PubMed

    Pereira-Caro, Gema; Ludwig, Iziar A; Polyviou, Thelma; Malkova, Dalia; García, Ada; Moreno-Rojas, José Manuel; Crozier, Alan

    2016-07-20

    Orange juice is a rich source of (poly)phenols, in particular, the flavanones hesperetin-7-O-rutinoside and naringenin-7-O-rutinoside. Following the acute consumption of 500 mL of orange juice containing 398 μmol of (poly)phenols by 12 volunteers, 0-24 h plasma and urine samples were analyzed by targeted high-performance liquid chromatography-high-resolution mass spectrometry in order to identify flavanone metabolites and phenolic acid and aromatic catabolites. A total of 19 flavanone metabolites-comprising di-O-glucuronide, O-glucuronide, O-glucuronyl-sulfate, and sulfate derivatives of hesperetin, naringenin, and eriodictyol-and 65 microbial-derived phenolic catabolites, such as phenylpropanoid, phenylpropionic, phenylacetic, benzoic, and hydroxycarboxylic acids and benzenetriol and benzoylglycine derivatives, including free phenolics and phase II sulfate, glucuronide, and methyl metabolites, were identified or partially identified in plasma and/or urine samples. The data obtained provide a detailed evaluation of the fate of orange juice (poly)phenols as they pass through the gastrointestinal tract and are absorbed into the circulatory system prior to renal excretion. Potential pathways for these conversions are proposed. PMID:27339035

  12. A study relating the composition of follicular fluid and blood plasma from individual Holstein dairy cows to the in vitro developmental competence of pooled abattoir-derived oocytes.

    PubMed

    Sutton-McDowall, Melanie L; Yelland, Robert; MacMillan, Keith L; Robker, Rebecca L; Thompson, Jeremy G

    2014-07-01

    The fertility of high-performance (high milk yield) dairy breeds such as the Holstein within the Australian dairy herd has been on the decline for the past two decades. The 12-month calving interval for pasture-based farming practices results in oocyte maturation coinciding with peak lactation, periods of negative energy balance, and energy partitioning for lactation, causing energy deficiency in some organ systems, including the reproductive system. Oocyte developmental competence (the ability to undergo successful fertilization, embryo development, and establishment of pregnancy) is intrinsically linked with the composition of follicular fluid (FF). The aim of this study was to determine if there was a relationship between the fat and carbohydrate levels in plasma and FF and the ability to support in vitro oocyte maturation (IVM). Plasma and FF were collected in vivo from eight Holstein cows between 52 and 151 days post-partum. Plasma glucose trended (P = 0.072) higher and triglyceride levels were significantly higher than in FF (P < 0.05), but there were no relationships between FF and plasma composition. Glucose FF concentration was negatively related to follicular lactate and nonesterified fatty acid (NEFA) levels and days post-partum. Conversely, FF triglyceride concentrations were positively related to FF NEFA levels and negatively related to milk fat and protein composition. Abattoir-derived cumulus-oocyte complexes were cultured in either 50% FF (FF-IVM) or 50% plasma (plasma-IVM), with on-time embryo development then assessed. Although there were no differences between animals, the blastocyst rates after FF-IVM were negatively related to plasma glucose and days post-partum and positively related to body condition score and plasma NEFA levels. In comparison to the previous studies, total NEFA levels in FF were not related to animal parameters and did not influence oocyte developmental competence in vitro. Results from this study suggest that days

  13. Validation of the safety of MDCK cells as a substrate for the production of a cell-derived influenza vaccine.

    PubMed

    Onions, David; Egan, William; Jarrett, Ruth; Novicki, Deborah; Gregersen, Jens-Peter

    2010-09-01

    Cell culture-based production methods may assist in meeting increasing demand for seasonal influenza vaccines and developing production flexibility required for addressing influenza pandemics. MDCK-33016PF cells are used in propagation of a cell-based seasonal influenza vaccine (Optaflu); but, like most continuous cell lines, can grow in immunocompromised mice to produce tumors. It is, therefore, essential that no residual cells remain within the vaccine, that cell lysates or DNA are not oncogenic, and that the cell substrate does not contain oncogenic viruses or oncogenic DNA. Multiple, redundant processes ensure the safety of influenza vaccines produced in MDCK-33016PF cells. The probability of a residual cell being present in a dose of vaccine is approximately 1 in 10(34). Residual MDCK-DNA is < or =10 ng per dose and the ss-propiolactone used to inactivate influenza virus results in reduction of detectable DNA to less than 200 base pairs (bp). Degenerate PCR and specific PCR confirm exclusion of oncogenic viruses. The manufacturing process has been validated for its capacity to remove and inactivate viruses. We conclude that the theoretical risks arising from manufacturing seasonal influenza vaccine using MDCK-33016PF cells are reduced to levels that are effectively zero by the multiple, orthogonal processes used during production. PMID:20537553

  14. Pharmacokinetics, brain distribution and plasma protein binding of carbamazepine and nine derivatives: new set of data for predictive in silico ADME models.

    PubMed

    Fortuna, Ana; Alves, Gilberto; Soares-da-Silva, Patrício; Falcão, Amílcar

    2013-11-01

    In silico approaches to predict absorption, distribution, metabolism and excretion (ADME) of new drug candidates are gaining a relevant importance in drug discovery programmes. When considering particularly the pharmacokinetics during the development of oral antiepileptic drugs (AEDs), one of the most prominent goals is designing compounds with good bioavailability and brain penetration. Thus, it is expected that in silico models able to predict these features may be applied during the early stages of AEDs discovery. The present investigation was mainly carried out in order to generate in vivo pharmacokinetic data that can be utilized for development and validation of in silico models. For this purpose, a single dose of each compound (1.4mmol/kg) was orally administered to male CD-1 mice. After quantifying the parent compound and main metabolites in plasma and brain up to 12h post-dosing, a non-compartmental pharmacokinetic analysis was performed and the corresponding brain/plasma ratios were calculated. Moreover the plasma protein binding was estimated in vitro applying the ultrafiltration procedure. The present in vivo pharmacokinetic characterization of the test compounds and corresponding metabolites demonstrated that the metabolism extensively compromised the in vivo activity of CBZ derivatives and their toxicity. Furthermore, it was clearly evidenced that the time to reach maximum peak concentration, bioavailability (given by the area under the curve) and metabolic stability (given by the AUC0-12h ratio of the parent compound and total systemic drug) influenced the in vivo pharmacological activities and must be considered as primary parameters to be investigated. All the test compounds presented brain/plasma ratios lower than 1.0, suggesting that the blood-brain barrier restricts drug entry into the brain. In agreement with in vitro studies already performed within our research group, CBZ, CBZ-10,11-epoxide and oxcarbazepine exhibited the highest brain/plasma

  15. A Phase II, Randomized, Safety and Immunogenicity Trial of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Children and Adults Living in Puerto Rico

    PubMed Central

    Bauer, Kristen; Esquilin, Ines O.; Cornier, Alberto Santiago; Thomas, Stephen J.; Quintero del Rio, Ana I.; Bertran-Pasarell, Jorge; Morales Ramirez, Javier O.; Diaz, Clemente; Carlo, Simon; Eckels, Kenneth H.; Tournay, Elodie; Toussaint, Jean-Francois; De La Barrera, Rafael; Fernandez, Stefan; Lyons, Arthur; Sun, Wellington; Innis, Bruce L.

    2015-01-01

    This was a double-blind, randomized, controlled, phase II clinical trial, two dose study of re-derived, live-attenuated, tetravalent dengue virus (TDEN) vaccine (two formulations) or placebo in subjects 1–50 years of age. Among the 636 subjects enrolled, 331 (52%) were primed, that is, baseline seropositive to at least one dengue virus (DENV) type. Baseline seropositivity prevalence increased with age (10% [< 2 years], 26% [2–4 years], 60% [5–20 years], and 93% [21–50 years]). Safety profiles of TDEN vaccines were similar to placebo regardless of priming status. No vaccine-related serious adverse events (SAEs) were reported. Among unprimed subjects, immunogenicity (geometric mean antibody titers [GMT] and seropositivity rates) for each DENV increased substantially in both TDEN vaccine groups with at least 74.6% seropositive for four DENV types. The TDEN vaccine candidate showed an acceptable safety and immunogenicity profile in children and adults ranging from 1 to 50 years of age, regardless of priming status. ClinicalTrials.gov: NCT00468858. PMID:26175027

  16. New Functionalities of PA6,6 Fabric Modified by Atmospheric Pressure Plasma and Grafted Glycidyl Methacrylate Derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative atmospheric pressure plasma was utilized to activate surface of PA 6,6 fabrics followed by graft copolymerization of glycidyl methacrylate (GMA) and further reacted with triethylene tetramine (TETA), quaternary ammonium chitosan (HTCC) or cyclodextrin (CD). The inner CD cavity was complexe...

  17. Detection of Plasma Protease Activity Using Microsphere-Cytometry Assays with E. coli Derived Substrates: VWF Proteolysis by ADAMTS13.

    PubMed

    Gogia, Shobhit; Lo, Chi Y; Neelamegham, Sriram

    2015-01-01

    Protease levels in human blood are often prognostic indicators of inflammatory, thrombotic or oncogenic disorders. The measurement of such enzyme activities in substrate-based assays is complicated due to the low prevalence of these enzymes and steric hindrance of the substrates by the more abundant blood proteins. To address these limitations, we developed a molecular construct that is suitable for microsphere-cytometer based assays in the milieu of human blood plasma. In this proof of principle study, we demonstrate the utility of this substrate to measure metalloprotease ADAMTS13 activity. The substrate, expressed in E. coli as a fusion protein, contains the partial A2-domain of von Willebrand factor (VWF amino acids 1594-1670) that is mutated to include a single primary amine at the N-terminus and free cysteines at the C-terminus. N-terminus fluorescence conjugation was possible using NHS (N-hydroxysuccinimide) chemistry. Maleimide-PEG(Polyethylene glycol)n-biotin coupling at the C-terminus allowed biotinylation with variable PEG spacer lengths. Once bound to streptavidin-bearing microspheres, the substrate fluorescence signal decreased in proportion with ADAMTS13 concentration. Whereas recombinant ADAMTS13 activity could be quantified using substrates with all PEG repeat-lengths, only the construct with the longer 77 PEG-unit could quantify proteolysis in blood plasma. Using this longer substrate, plasma ADAMTS13 down to 5% of normal levels could be detected within 30 min. Such measurements could also be readily performed under conditions resembling hyperbilirubinemia. Enzyme catalytic activity was tuned by varying buffer calcium, with lower divalent ion concentrations enhancing cleavage. Overall, the study highlights the substrate design features important for the creation of efficient proteolysis assays in the setting of human plasma. In particular, it emphasizes the need to introduce PEG spacers in plasma-based experiments, a design attribute commonly

  18. Detection of Plasma Protease Activity Using Microsphere-Cytometry Assays with E. coli Derived Substrates: VWF Proteolysis by ADAMTS13

    PubMed Central

    Gogia, Shobhit; Lo, Chi Y.; Neelamegham, Sriram

    2015-01-01

    Protease levels in human blood are often prognostic indicators of inflammatory, thrombotic or oncogenic disorders. The measurement of such enzyme activities in substrate-based assays is complicated due to the low prevalence of these enzymes and steric hindrance of the substrates by the more abundant blood proteins. To address these limitations, we developed a molecular construct that is suitable for microsphere-cytometer based assays in the milieu of human blood plasma. In this proof of principle study, we demonstrate the utility of this substrate to measure metalloprotease ADAMTS13 activity. The substrate, expressed in E. coli as a fusion protein, contains the partial A2-domain of von Willebrand factor (VWF amino acids 1594–1670) that is mutated to include a single primary amine at the N-terminus and free cysteines at the C-terminus. N-terminus fluorescence conjugation was possible using NHS (N-hydroxysuccinimide) chemistry. Maleimide-PEG(Polyethylene glycol)n-biotin coupling at the C-terminus allowed biotinylation with variable PEG spacer lengths. Once bound to streptavidin-bearing microspheres, the substrate fluorescence signal decreased in proportion with ADAMTS13 concentration. Whereas recombinant ADAMTS13 activity could be quantified using substrates with all PEG repeat-lengths, only the construct with the longer 77 PEG-unit could quantify proteolysis in blood plasma. Using this longer substrate, plasma ADAMTS13 down to 5% of normal levels could be detected within 30 min. Such measurements could also be readily performed under conditions resembling hyperbilirubinemia. Enzyme catalytic activity was tuned by varying buffer calcium, with lower divalent ion concentrations enhancing cleavage. Overall, the study highlights the substrate design features important for the creation of efficient proteolysis assays in the setting of human plasma. In particular, it emphasizes the need to introduce PEG spacers in plasma-based experiments, a design attribute commonly

  19. Development and validation of a UHPLC-UV method for the determination of a prostate secretory protein 94-derived synthetic peptide (PCK3145) in human plasma and assessment of its stability in human plasma.

    PubMed

    El Mubarak, Mohamed A; Leontari, Iliana; Danika, Charikleia; Katsila, Theodora; Sivolapenko, Gregory

    2016-09-01

    PCK3145 is a synthetic peptide, derived from the Prostate Secreted Protein 94 (PSP94), with promising in vitro and animal in vivo results in prostate cancer. The aim of the present study was to develop and validate a fast and robust ultra-high-performance liquid chromatography with ultraviolet detection for the determination of PCK3145 in human plasma which would be suitable for the assessment of PCK3145 stability to proteolytic degradation. Following protein precipitation, chromatographic separation was carried out on an Aeris Peptide C18 column with mobile phase consisting of acetonitrile-water at a flow-rate of 0.50 mL/min. The calibration curve was linear over the range 0.50-20.00 μg/mL. Intra- and inter-day percentage relative standard deviation and relative error were ≤10%. The limit of detection and the lower limit of quantification were 0.15 and 0.50 μg/mL, respectively. Recovery of PCK3145 from human plasma was ≥96%. The peptide presented high stability in whole blood and in human plasma (>98% intact peptide after 24 h incubation at 37°C in human plasma), which represents a distinctive advantage in the therapeutic use of the compound. This is the first validated UHPLC method for the determination of PCK3145 reported, and it was successfully applied in the study of the proteolytic stability of PCK3145 in human plasma ex vivo. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26892539

  20. Human Hepatocyte-Derived Induced Pluripotent Stem Cells: MYC Expression, Similarities to Human Germ Cell Tumors, and Safety Issues

    PubMed Central

    Unzu, Carmen; Friedli, Marc; Bosman, Alexis; Jaconi, Marisa E.; Wildhaber, Barbara E.; Rougemont, Anne-Laure

    2016-01-01

    Induced pluripotent stem cells (iPSC) are a most promising approach to the development of a hepatocyte transplantable mass sufficient to induce long-term correction of inherited liver metabolic diseases, thus avoiding liver transplantation. Their intrinsic self-renewal ability and potential to differentiate into any of the three germ layers identify iPSC as the most promising cell-based therapeutics, but also as drivers of tumor development. Teratoma development currently represents the gold standard to assess iPSC pluripotency. We analyzed the tumorigenic potential of iPSC generated from human hepatocytes (HEP-iPSC) and compared their immunohistochemical profiles to that of tumors developed from fibroblast and hematopoietic stem cell-derived iPSC. HEP-iPSC generated tumors significantly presented more malignant morphological features than reprogrammed fibroblasts or CD34+ iPSC. Moreover, the protooncogene myc showed the strongest expression in HEP-iPSC, compared to only faint expression in the other cell subsets. Random integration of transgenes and the use of potent protooncogenes such as myc might be a risk factor for malignant tumor development if hepatocytes are used for reprogramming. Nonviral vector delivery systems or reprogramming of cells obtained from less invasive harvesting methods would represent interesting options for future developments in stem cell-based approaches for liver metabolic diseases. PMID:26880963

  1. Plasma Derived From Human Umbilical Cord Blood Modulates Mitogen-Induced Proliferation of Mononuclear Cells Isolated From the Peripheral Blood of ALS Patients.

    PubMed

    Eve, David J; Ehrhart, Jared; Zesiewicz, Theresa; Jahan, Israt; Kuzmin-Nichols, Nicole; Sanberg, Cyndy Davis; Gooch, Clifton; Sanberg, Paul R; Garbuzova-Davis, Svitlana

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration of motor neurons in the spinal cord and brain. This disease clinically manifests as gradual muscular weakness and atrophy leading to paralysis and death by respiratory failure. While multiple interdependent factors may contribute to the pathogenesis of ALS, increasing evidence shows the possible presence of autoimmune mechanisms that promote disease progression. The potential use of plasma derived from human umbilical cord blood (hUCB) as a therapeutic tool is currently in its infancy. The hUCB plasma is rich in cytokines and growth factors that are required for growth and survival of cells during hematopoiesis. In this study, we investigated the effects of hUCB plasma on the mitogen-induced proliferation of mononuclear cells (MNCs) isolated from the peripheral blood of ALS patients and apoptotic activity by detection of caspase 3/7 expression of the isolated MNCs in vitro. Three distinct responses to phytohemagglutinin (PHA)-induced proliferation of MNCs were observed, which were independent of age, disease duration, and the ALS rating scale: Group I responded normally to PHA, Group II showed no response to PHA, while Group III showed a hyperactive response to PHA. hUCB plasma attenuated the hyperactive response (Group III) and potentiated the normal response in Group I ALS patients, but did not alter that of the nonresponders to PHA (Group II). The elevated activity of caspase 3/7 observed in the MNCs from ALS patients was significantly reduced by hUCB plasma treatment. Thus, study results showing different cell responses to mitogen suggest alteration in lymphocyte functionality in ALS patients that may be a sign of immune deficiency in the nonresponders and autoimmunity alterations in the hyperactive responders. The ability of hUCB plasma to modulate the mitogen cell response and reduce caspase activity suggests that the use of hUCB plasma alone, or with

  2. CHANGES IN PLASMA MULLERIAN INHIBITING SUBSTANCE AND BRAIN-DERIVED NEUROTROPHIC FACTOR AFTER CHEMOTHERAPY IN PREMENOPAUSAL WOMEN

    PubMed Central

    Aslam, Muhammad Faisal; Merhi, Zaher O; Ahmed, Safaa; Kuzbari, Oumar; Seifer, David B.; Minkoff, Howard

    2010-01-01

    Eight premenopausal women with cancer had blood drawn for brain-derived neurotrophic factor (BDNF) and Mullerian Inhibiting Substance (MIS) before and three months after receiving chemotherapy. Unlike MIS, BDNF levels were not reduced following chemotherapy. PMID:21075370

  3. Proof of concept studies exploring the safety and functional activity of human parthenogenetic-derived neural stem cells for the treatment of Parkinson's disease.

    PubMed

    Gonzalez, Rodolfo; Garitaonandia, Ibon; Crain, Andrew; Poustovoitov, Maxim; Abramihina, Tatiana; Noskov, Alexander; Jiang, Chuan; Morey, Robert; Laurent, Louise C; Elsworth, John D; Snyder, Evan Y; Redmond, D Eugene; Semechkin, Ruslan

    2015-01-01

    Recent studies indicate that human pluripotent stem cell (PSC)-based therapies hold great promise in Parkinson's disease (PD). Clinical studies have shown that grafted fetal neural tissue can achieve considerable biochemical and clinical improvements in PD. However, the source of fetal tissue grafts is limited and ethically controversial. Human parthenogenetic stem cells offer a good alternative because they are derived from unfertilized oocytes without destroying viable human embryos and can be used to generate an unlimited supply of neural stem cells for transplantation. Here we evaluate for the first time the safety and engraftment of human parthenogenetic stem cell-derived neural stem cells (hpNSCs) in two animal models: 6-hydroxydopamine (6-OHDA)-lesioned rodents and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primates (NHPs). In both rodents and nonhuman primates, we observed successful engraftment and higher dopamine levels in hpNSC-transplanted animals compared to vehicle control animals, without any adverse events. These results indicate that hpNSCs are safe, well tolerated, and could potentially be a source for cell-based therapies in PD. PMID:25839189

  4. Anticonvulsant activity, crystal structures, and preliminary safety evaluation of N-trans-cinnamoyl derivatives of selected (un)modified aminoalkanols.

    PubMed

    Gunia-Krzyżak, Agnieszka; Żesławska, Ewa; Słoczyńska, Karolina; Koczurkiewicz, Paulina; Nitek, Wojciech; Żelaszczyk, Dorota; Szkaradek, Natalia; Waszkielewicz, Anna M; Pękala, Elżbieta; Marona, Henryk

    2016-01-01

    Adequate control of seizures remains an unmet need in epilepsy. In order to identify new anticonvulsant agents, a series of N-trans-cinnamoyl derivatives of selected aminoalkanols was synthetized. The compounds were obtained in the reaction of N-acylation carried out in a two-phase system. The substances were tested in animal models of seizures induced either electrically (maximal electroshock--MES; 6-Hz test) or chemically, by subcutaneous injection of pentetrazol (scPTZ). Neurotoxicity was determined by the rotarod test. Lipophilicity of the active compounds, expressed as RM0, was determined by reversed-phase thin layer chromatography and it ranged from 1.390 to 2.219. From among the tested series of compounds, R,S-(E)-N-(1-hydroxypropan-2-yl)-3-phenylprop-2-enamide (1) and R,S-(E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide (3) exhibited the best anticonvulsant activity. Compound 1, when administered to mice by intraperitoneal (i.p.) injection, showed the ED50 values of 86.6, 60.9, and 109.6 mg/kg in the MES, 6-Hz, and scPTZ tests, respectively. For compound 3, the ED50 values were found to be 47.1 mg/kg in MES and 77.1 mg/kg in scPTZ (mice, i.p.). The distances measured in crystals of compound 1 were: 7.99 Å--from the phenyl ring to the hydroxyl group in the amide moiety, 5.729 Å--from the phenyl ring to the amide group, and 3.112 Å--from the amide group to the hydroxyl group in the amide moiety. The reported compounds did not exhibit mutagenic potential when assayed in the Ames test. Compounds 1 and 3 did not affect viability and morphology of human hepatocellular carcinoma cells (HepG2). PMID:26560050

  5. Laboratory spectroscopic diagnostics of TLE-like air plasmas: methods to derive the rotational (gas) temperature in TLEs

    NASA Astrophysics Data System (ADS)

    Gordillo-Vazquez, F.; Parra-Rojas, F.; Passas, M.; Carrasco, E.; Luque, A.; Tanarro, I.; Simek, M.

    2013-12-01

    Laboratory low pressure (0.1 mbar < p < 2 mbar) glow air discharges have been studies by optical emission spectroscopy to illustrate several spectroscopic techniques that, depending on the available spectral resolution, could be implemented by different field spectrographs to experimentally quantify the gas temperature associated with Transient Luminous Events (TLEs) occurring at different altitudes including blue jets, giant blue jets and sprites. The laboratory air plasmas investigated have been analysed from the near UV (300 nm) to the near IR (1060 nm) with high (up to 0.01 nm) and low (2 nm) spectral resolution commercial grating spectrographs and by an in-house developed intensified CCD grating spectrograph that we have recently developed in our group at IAA - CSIC for TLE spectral diagnostic surveys with 0.45 nm spectral resolution. We discuss the results of laboratory tests and comment on the convenience of using one or another technique for rotational (gas) temperature determination during TLE spectroscopic campaigns. Finally, we will also show a comparison of the vibrational distribution function (VDF) of N2(B) obtained from (a) experiments in low pressure laboratory air plasmas produced in conditions similar to TLEs, (b) spectroscopic emissions from real TLE air plasmas and (c) compute from kinetic modeling.

  6. Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine.

    PubMed

    Yamamori, Hidenaga; Hashimoto, Ryota; Ishima, Tamaki; Kishi, Fukuko; Yasuda, Yuka; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Ito, Akira; Hashimoto, Kenji; Takeda, Masatoshi

    2013-11-27

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. Peripheral BDNF levels in patients with schizophrenia have been widely reported in the literature. However, it is still controversial whether peripheral levels of BDNF are altered in patients with schizophrenia. The peripheral BDNF levels previously reported in patients with schizophrenia were total BDNF (proBDNF and mature BDNF) as it was unable to specifically measure mature BDNF due to limited BDNF antibody specificity. In this study, we examined whether peripheral levels of mature BDNF were altered in patients with treatment-resistant schizophrenia. Matrix metalloproteinase-9 (MMP-9) levels were also measured, as MMP-9 plays a role in the conversion of proBDNF to mature BDNF. Twenty-two patients with treatment-resistant schizophrenia treated with clozapine and 22 age- and sex-matched healthy controls were enrolled. The plasma levels of mature BDNF and MMP-9 were measured using ELISA kits. No significant difference was observed for mature BDNF however, MMP-9 was significantly increased in patients with schizophrenia. The significant correlation was observed between mature BDNF and MMP-9 plasma levels. Neither mature BDNF nor MMP-9 plasma levels were associated clinical variables. Our results do not support the view that peripheral BDNF levels are associated with schizophrenia. MMP-9 may play a role in the pathophysiology of schizophrenia and serve as a biomarker for schizophrenia. PMID:24141084

  7. Low-temperature plasma etching of high aspect-ratio densely packed 15 to sub-10 nm silicon features derived from PS-PDMS block copolymer patterns

    NASA Astrophysics Data System (ADS)

    Liu, Zuwei; Gu, Xiaodan; Hwu, Justin; Sassolini, Simone; Olynick, Deirdre L.

    2014-07-01

    The combination of block copolymer (BCP) lithography and plasma etching offers a gateway to densely packed sub-10 nm features for advanced nanotechnology. Despite the advances in BCP lithography, plasma pattern transfer remains a major challenge. We use controlled and low substrate temperatures during plasma etching of a chromium hard mask and then the underlying substrate as a route to high aspect ratio sub-10 nm silicon features derived from BCP lithography. Siloxane masks were fabricated using poly(styrene-b-siloxane) (PS-PDMS) BCP to create either line-type masks or, with the addition of low molecular weight PS-OH homopolymer, dot-type masks. Temperature control was essential for preventing mask migration and controlling the etched feature’s shape. Vertical silicon wire features (15 nm with feature-to-feature spacing of 26 nm) were etched with aspect ratios up to 17 : 1; higher aspect ratios were limited by the collapse of nanoscale silicon structures. Sub-10 nm fin structures were etched with aspect ratios greater than 10 : 1. Transmission electron microscopy images of the wires reveal a crystalline silicon core with an amorphous surface layer, just slightly thicker than a native oxide.

  8. Central safety factor and βN control on NSTX-U via beam power and plasma boundary shape modification, using TRANSP for closed loop simulations

    NASA Astrophysics Data System (ADS)

    Boyer, M. D.; Andre, R.; Gates, D. A.; Gerhardt, S.; Goumiri, I. R.; Menard, J.

    2015-05-01

    The high-performance operational goals of NSTX-U will require development of advanced feedback control algorithms, including control of βN and the safety factor profile. In this work, a novel approach to simultaneously controlling βN and the value of the safety factor on the magnetic axis, q0, through manipulation of the plasma boundary shape and total beam power, is proposed. Simulations of the proposed scheme show promising results and motivate future experimental implementation and eventual integration into a more complex current profile control scheme planned to include actuation of individual beam powers, density, and loop voltage. As part of this work, a flexible framework for closed loop simulations within the high-fidelity code TRANSP was developed. The framework, used here to identify control-design-oriented models and to tune and test the proposed controller, exploits many of the predictive capabilities of TRANSP and provides a means for performing control calculations based on user-supplied data (controller matrices, target waveforms, etc). The flexible framework should enable high-fidelity testing of a variety of control algorithms, thereby reducing the amount of expensive experimental time needed to implement new control algorithms on NSTX-U and other devices.

  9. Vesicular Galectin-3 levels decrease with donor age and contribute to the reduced osteo-inductive potential of human plasma derived extracellular vesicles

    PubMed Central

    Weilner, Sylvia; Keider, Verena; Winter, Melanie; Harreither, Eva; Salzer, Benjamin; Weiss, Florian; Schraml, Elisabeth; Messner, Paul; Pietschmann, Peter; Hildner, Florian; Gabriel, Christian; Redl, Heinz; Grillari-Voglauer, Regina; Grillari, Johannes

    2016-01-01

    Aging results in a decline of physiological functions and in reduced repair capacities, in part due to impaired regenerative power of stem cells, influenced by the systemic environment. In particular osteogenic differentiation capacity (ODC) of mesenchymal stem cells (MSCs) has been shown to decrease with age, thereby contributing to reduced bone formation and an increased fracture risk. Searching for systemic factors that might contribute to this age related decline of regenerative capacity led us to investigate plasma-derived extracellular vesicles (EVs). EVs of the elderly were found to inhibit osteogenesis compared to those of young individuals. By analyzing the differences in the vesicular content Galectin-3 was shown to be reduced in elderly-derived vesicles. While overexpression of Galectin-3 resulted in an enhanced ODC of MSCs, siRNA against Galectin-3 reduced osteogenesis. Modulation of intravesicular Galectin-3 levels correlated with an altered osteo-inductive potential indicating that vesicular Galectin-3 contributes to the biological response of MSCs to EVs. By site-directed mutagenesis we identified a phosphorylation-site on Galectin-3 mediating this effect. Finally, we showed that cell penetrating peptides comprising this phosphorylation-site are sufficient to increase ODC in MSCs. Therefore, we suggest that decrease of Galectin-3 in the plasma of elderly contributes to the age-related loss of ODC. PMID:26752347

  10. Vesicular Galectin-3 levels decrease with donor age and contribute to the reduced osteo-inductive potential of human plasma derived extracellular vesicles.

    PubMed

    Weilner, Sylvia; Keider, Verena; Winter, Melanie; Harreither, Eva; Salzer, Benjamin; Weiss, Florian; Schraml, Elisabeth; Messner, Paul; Pietschmann, Peter; Hildner, Florian; Gabriel, Christian; Redl, Heinz; Grillari-Voglauer, Regina; Grillari, Johannes

    2016-01-01

    Aging results in a decline of physiological functions and in reduced repair capacities, in part due to impaired regenerative power of stem cells, influenced by the systemic environment. In particular osteogenic differentiation capacity (ODC) of mesenchymal stem cells (MSCs) has been shown to decrease with age, thereby contributing to reduced bone formation and an increased fracture risk. Searching for systemic factors that might contribute to this age related decline of regenerative capacity led us to investigate plasma-derived extracellular vesicles (EVs). EVs of the elderly were found to inhibit osteogenesis compared to those of young individuals. By analyzing the differences in the vesicular content Galectin-3 was shown to be reduced in elderly-derived vesicles. While overexpression of Galectin-3 resulted in an enhanced ODC of MSCs, siRNA against Galectin-3 reduced osteogenesis. Modulation of intravesicular Galectin-3 levels correlated with an altered osteo-inductive potential indicating that vesicular Galectin-3 contributes to the biological response of MSCs to EVs. By site-directed mutagenesis we identified a phosphorylation-site on Galectin-3 mediating this effect. Finally, we showed that cell penetrating peptides comprising this phosphorylation-site are sufficient to increase ODC in MSCs. Therefore, we suggest that decrease of Galectin-3 in the plasma of elderly contributes to the age-related loss of ODC. PMID:26752347

  11. Universal immunization of infants with low doses of a low-cost, plasma-derived hepatitis B vaccine in South Africa.

    PubMed Central

    Schoub, B. D.; Matai, U.; Singh, B.; Blackburn, N. K.; Levin, J. B.

    2002-01-01

    OBJECTIVE: To evaluate the effectiveness of universal vaccination against viral hepatitis B in South Africa among 18-month-old rural children. METHODS: Children were immunized with a course of low-dose (1.5 microg), plasma-derived hepatitis B vaccine at 6, 10 and 14 weeks of age, and blood samples from the children were tested for three hepatitis B markers: hepatitis B surface antigen (HBsAg), anti-HBs and anti-HBc. FINDINGS: One year after vaccination, a protective anti-HBs antibody titre of at least 10 IU/l was present in 669/769 (87.0%) of blood serum samples tested. Only 3/756 children (0.4%) were HBsAg positive and a fourth child was anti-HBc positive (HBsAg negative). This is a marked decrease compared to the hepatitis B prevalences reported in previous studies. Among rural migrant mine-workers, for example, HBsAg prevalence was 9.9%, and was 10.1% among children 0-6 years of age in the Eastern Cape Province. CONCLUSION: The low-dose, plasma-derived hepatitis B vaccine, which is affordable to most developing countries, was very successful in controlling endemic hepatitis B infection, where the virus is predominantly spread by horizontal transmission among infants and young children. PMID:12075363

  12. Spectrofluorimetric Determination of Topiramate and Levetiracetam as Single Components in Tablet Formulations and in Human Plasma and Simultaneous Fourth Derivative Synchronous Fluorescence Determination of their Co-Adminstered Mixture in Human Plasma.

    PubMed

    El-Yazbi, A F; Wagih, M M; Ibrahim, F; Barary, M A

    2016-07-01

    Two highly sensitive, rapid, simple, economic and validated spectrofluorimetric methods have been developed for determination of Topiramate and Levetiracetam in pharmaceutical tablets and in human plasma. Topiramate and Levetiracetam were determined separately by derivatization using 4-Chloro-7-nitrobenzofuran-2-oxo-1,3-diazole (NBD-Cl) and measured spectrofluorimetrically. The Relative fluorescence intensities were measured at λem/ex of 547/465 nm and 551/465 nm for Topiramate and Levetiracetam, respectively. While a binary mixture of Topiramate and Levetiracetam were determined by the fourth derivative synchronous fluorescence measurement after their reaction with NBD-Cl. In this method, the fourth derivative synchronous spectra were estimated as peak to peak measurement at 493-497 and 490.5-495 nm corresponding with zero-contribution of Levetiracetam and Topiramate, respectively. Linearity ranges for Topiramate and Levetiracetam in both methods were found to be 0.15-1.2 and 0.2-1.5 μg/mL, respectively. The different experimental parameters affecting the fluorescence of the two drugs were carefully studied and optimized. The proposed methods were validated in terms of linearity, accuracy, precision, limits of detection and quantification and other aspects of analytical validation. The proposed methods were successfully applied for the determination of the investigated drugs in human plasma samples obtained from healthy volunteers after single oral administration of the two drugs. PMID:27147226

  13. Phase III Clinical Trials Comparing the Immunogenicity and Safety of the Vero Cell-Derived Japanese Encephalitis Vaccine Encevac with Those of Mouse Brain-Derived Vaccine by Using the Beijing-1 Strain

    PubMed Central

    Miyazaki, Chiaki; Okada, Kenji; Ozaki, Takao; Hirose, Mizuo; Iribe, Kaneshige; Ishikawa, Yuji; Togashi, Takehiro; Ueda, Kohji

    2014-01-01

    The immunogenicity and safety of an inactivated cell culture Japanese encephalitis vaccine (CC-JEV) were compared with those of an inactivated mouse brain-derived Japanese encephalitis vaccine (MB-JEV) in phase III clinical multicenter trials conducted in children. The vaccines contain the same Japanese encephalitis virus strain, the Beijing-1 strain. Two independent clinical trials (trials 1 and 2) were conducted. Trial 1 was conducted in 468 healthy children. Each subject was injected with 17 μg per dose of either CC-JEV or MB-JEV, and the immunogenicity and safety of the vaccines were investigated. Trial 1 showed that CC-JEV was more immunogenic and reactive than MB-JEV at the same dose. Therefore, to adjust the immunogenicity of CC-JEV to that of MB-JEV, a vaccine that has had a good track record regarding its efficacy for a long time, trial 2 was conducted in 484 healthy children. To improve the stability, CC-JEV was converted from a liquid type to a freeze-dried type of vaccine. Each subject was injected subcutaneously with either 4 μg per dose of CC-JEV, 8 μg per dose of CC-JEV, or 17 μg per dose of MB-JEV twice, at an interval of 2 to 4 weeks, followed by an additional booster immunization 1 to 15 months after the primary immunization. Based on the results of trial 2, 4 μg per dose of the freeze-dried CC-JEV (under the label Encevac) was selected as a substitute for the MB-JEV. Encevac was approved and launched in 2011 and has since been in use as a 2nd-generation Japanese encephalitis vaccine in Japan. (These studies have been registered at the JapicCTI under registration no. JapicCTI-132063 and JapicCTI-080586 for trials 1 and 2, respectively.) PMID:24334689

  14. The determination of oestradiol and oestrone in the plasma of the domestic fowl by a method involving the use of labelled derivatives

    PubMed Central

    O'Grady, J. E.

    1968-01-01

    1. A method involving the use of triple-labelled derivatives has been developed for the determination of total oestrone and oestradiol in the plasma of the domestic fowl. The double-labelling technique devised by Svendsen (1960) for the determination of free oestrogens in human plasma was modified to enable the total oestrogen recovery to be determined for each sample. 2. [6,7-3H2]Oestradiol-17β is added to the plasma samples (1–10ml.), which are hydrolysed with acid and the phenolic steroids then extracted and partially purified. The extract is esterified with iodobenzene-p[35S]-sulphonyl chloride of high specific activity. After addition of standard oestrogen [131I]iodobenzene-p-sulphonates the esters are finally purified by paper chromatography. 3. The oestrogens are determined by comparing the 3H/35S and 131I/35S ratios in the purified esters with similar ratios of appropriate standards. 4. With this procedure the recoveries of oestrone and oestradiol after hydrolysis were 70–85% and 72–84% respectively, and after hydrolysis and preliminary purification 38–53% and 39–51% respectively. With this procedure up to 500ng. of oestradiol can be determined. The sensitivity of the technique for oestrone is 3·0ng. and for oestradiol 2·1ng. 5. The ranges of oestradiol and oestrone concentrations found in six plasma samples were 8·3–21·4ng./ml. and 15·2–31·6ng./ml. respectively. PMID:5721473

  15. Alfvén wave characteristics of equatorial plasma irregularities in the ionosphere derived from CHAMP observations

    NASA Astrophysics Data System (ADS)

    Lühr, Hermann; Park, Jaeheung; Xiong, Chao; Xiong, Chao; Rauberg, Jan

    2014-08-01

    We report magnetic field observations of the components transverse to the main field in the frequency range 1-25 Hz from times of equatorial plasma irregularity crossings. These field variations are interpreted as Alfvénic signatures accompanying intermediate-scale (150 m - 4 km) plasma density depletions. Data utilized are the high-resolution CHAMP magnetic field measurements sampled at 50 Hz along the north-south satellite track. The recorded signals do not reflect the temporal variation but the spatial distribution of Alfvénic signatures. This is the first comprehensive study of Alfvénic signatures related to equatorial plasma bubbles that covers the whole solar cycle from 2000 to 2010. A detailed picture of the wave characteristics can be drawn due to the large number (almost 9000) of events considered. Some important findings are: Alfvénic features are a common feature of intermediate-scale plasma structures. The zonal and meridional magnetic components are generally well correlated suggesting skewed current sheets. The sheets have an orientation that is on average deflect by about 32° away from magnetic east towards upward or downward depending on the hemisphere. We have estimated the Poynting flux flowing into the E region. Typical values are distributed over the range 10-8 - 10-6 W/m2. Large Poynting fluxes are related to steep spectra of the Alfvénic signal, which imply passages through regularly varying electron density structures. No dependence of the Poynting flux level on solar activity has been found. But below a certain solar flux value (F10.7 < 100 sfu) practically no events are detected. There is a clear tendency that large Poynting flux events occur preferably at early hours after sunset (e.g. 20:00 local time). Towards later times the occurrence peak shifts successively towards lower energy levels. Finally we compare our observations with the recently published results of the high-resolution 3-D model simulations by Dao et al. (2013).

  16. Hand Safety

    MedlinePlus

    ... Fireworks Safety Lawnmower Safety Snowblower safety Pumpkin Carving Gardening Safety Turkey Carving Removing a Ring Español Artritis ... Fireworks Safety Lawnmower Safety Snowblower safety Pumpkin Carving Gardening Safety Turkey Carving Removing a Ring Español Artritis ...

  17. Hand Safety

    MedlinePlus

    ... en gatillo See More... Hand Anatomy Hand Safety Fireworks Safety Lawnmower Safety Snowblower safety Pumpkin Carving Gardening ... en gatillo See More... Hand Anatomy Hand Safety Fireworks Safety Lawnmower Safety Snowblower safety Pumpkin Carving Gardening ...

  18. Immunogenicity and safety of cell-derived MF59®-adjuvanted A/H1N1 influenza vaccine for children

    PubMed Central

    Knuf, Markus; Leroux-Roels, Geert; Rümke, Hans; Rivera, Luis; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria; Kieninger, Dorothee; Cioppa, Giovanni Della

    2015-01-01

    Mass immunization of children has the potential to decrease infection rates and prevent the transmission of influenza. We evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a randomized, single-blind, multicenter study with a total of 666 healthy subjects aged 6 months–17 y in one of 3 vaccination groups, each receiving formulations containing different amounts of influenza A/H1N1 antigen with or without MF59. A booster trivalent seasonal MF59 vaccine was administered one year after primary vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Safety was monitored throughout the study. One vaccination with 3.75 μg of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5 μg of A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer ≥1:40 in >70% of children in the 1–<3, 3–8, and 9–17 y cohorts; however, 2 vaccinations with nonadjuvanted 15 μg A/H1N1 antigen were needed to achieve this response in the 1–<3 and 3–8 y cohorts. Among children aged 6–11 months, 1 dose of 7.5_fullMF59 resulted in an HI titer ≥1:40 in >70% while 2 doses of 3.75_halfMF59 were required to achieve this result. All vaccines were well tolerated. Our findings support the immunogenicity and safety of the 3.75_halfMF59 (2 doses for children <12 months) and 7.5_fullMF59 vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 3.75_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people. PMID:25621884

  19. Low-n magnetohydrodynamic edge instabilities in quiescent H-mode plasmas with a safety-factor plateau

    NASA Astrophysics Data System (ADS)

    Zheng, L. J.; Kotschenreuther, M. T.; Valanju, P.

    2013-06-01

    Low-n magnetohydrodynamic (MHD) modes in the quiescent high confinement mode (H-mode) pedestal are investigated in this paper. Here, n is the toroidal mode number. The low collisionality regime is considered, so that a safety-factor plateau arises in the pedestal region because of the strong bootstrap current. The JET-like (Joint European Torus) equilibria of quiescent H-mode discharges are generated numerically using the VMEC code. The stability of this type of equilibria is analysed using the AEGIS code, with subsonic rotation effects taken into account. The current investigation extends the previous studies of n = 1 modes to n = 2 and 3 modes. The numerical results show that the MHD instabilities in this type of equilibria have characteristic features of the infernal mode. We find that this type of mode tends to prevail when the safety-factor value in the shear-free region is slightly larger than an integer. In this case the frequencies (ωn) of modes with toroidal mode number n roughly follow the rule ωn ˜ -nΩp, where Ωp is the local rotation frequency where the infernal harmonic prevails. Since the infernal mode tends to develop near the pedestal top, where pressure driving is strong but magnetic shear stabilization is weak, this local rotation frequency tends to be close to the pedestal top value. These typical mode features bear close resemblance to the edge harmonic oscillations (or outer modes) at the quiescent H-mode discharges observed experimentally.

  20. Correlation of nuclear criticality safety computer codes with plutonium benchmark experiments and derivation of subcritical limits. [MGBS, TGAN, KEFF, HRXN, GLASS, ANISN, SPBL, and KENO

    SciTech Connect

    Clark, H.K.

    1981-10-01

    A compilation of benchmark critical experiments was made for essentially one-dimensional systems containing plutonium. The systems consist of spheres, series of experiments with cylinders and cuboids that permit extrapolation to infinite cylinders and slabs, and large cylinders for which separability of the neutron flux into a product of spatial components is a good approximation. Data from the experiments were placed in a form readily usable as computer code input. Aqueous solutions of Pu(NO/sub 3/)/sub 4/ are treated as solutions of PuO/sub 2/ in nitric acid. The apparent molal volume of PuO/sub 2/ as a function of plutonium concentration was derived from analyses of solution density data and was incorporated in the Savannah River Laboratory computer codes along with density tables for nitric acid. The biases of three methods of calculation were established by correlation with the benchmark experiments. The oldest method involves two-group diffusion theory and has been used extensively at the Savannah River Laboratory. The other two involve S/sub n/ transport theory with, in one method, Hansen-Roach cross sections and, in the other, cross sections derived from ENDF/B-IV. Subcritical limits were calculated by all three methods. Significant differences were found among the results and between the results and limits currently in the American National Standard for Nuclear Criticality Safety in Operations with Fissionable Materials Outside Reactor (ANSI N16.1), which were calculated by yet another method, despite the normalization of all four methods to the same experimental data. The differences were studied, and a set of subcritical limits was proposed to supplement and in some cases to replace those in the ANSI Standard, which is currently being reviewed.

  1. Growth Conditions and Cell Cycle Phase Modulate Phase Transition Temperatures in RBL-2H3 Derived Plasma Membrane Vesicles

    PubMed Central

    Gray, Erin M.; Díaz-Vázquez, Gladys; Veatch, Sarah L.

    2015-01-01

    Giant plasma membrane vesicle (GPMV) isolated from a flask of RBL-2H3 cells appear uniform at physiological temperatures and contain coexisting liquid-ordered and liquid-disordered phases at low temperatures. While a single GPMV transitions between these two states at a well-defined temperature, there is significant vesicle-to-vesicle heterogeneity in a single preparation of cells, and average transition temperatures can vary significantly between preparations. In this study, we explore how GPMV transition temperatures depend on growth conditions, and find that average transition temperatures are negatively correlated with average cell density over 15°C in transition temperature and nearly three orders of magnitude in average surface density. In addition, average transition temperatures are reduced by close to 10°C when GPMVs are isolated from cells starved of serum overnight, and elevated transition temperatures are restored when serum-starved cells are incubated in serum-containing media for 12h. We also investigated variation in transition temperature of GPMVs isolated from cells synchronized at the G1/S border through a double Thymidine block and find that average transition temperatures are systematically higher in GPMVs produced from G1 or M phase cells than in GPMVs prepared from S or G1 phase cells. Reduced miscibility transition temperatures are also observed in GPMVs prepared from cells treated with TRAIL to induce apoptosis or sphingomyelinase, and in some cases a gel phase is observed at temperatures above the miscibility transition in these vesicles. We conclude that at least some variability in GPMV transition temperature arises from variation in the local density of cells and asynchrony of the cell cycle. It is hypothesized that GPMV transition temperatures are a proxy for the magnitude of lipid-mediated membrane heterogeneity in intact cell plasma membranes at growth temperatures. If so, these results suggest that cells tune their plasma membrane

  2. SuperDARN-derived plasma convection: Comparison with other data and application to field-aligned current measurements

    NASA Astrophysics Data System (ADS)

    Xu, Liang

    In this thesis, several aspects of the SuperDARN HF radar observations at high latitudes are investigated in cooperation with measurements performed by three other instruments, the Sondrestrom incoherent scatter radar, the ion drift meter onboard of the DMSP satellite and the CADI ionosonde. The first issue under investigation was consistency of plasma convection data provided by these instruments. First, routine measurements by the Goose Bay and Stokkseyri SuperDARN radar pair ("merge" velocity estimates) were compared with the Sondrestrom incoherent scatter radar data. Three different levels of assessment were used; by looking at the line-of-sight velocities, by comparing the SuperDARN vectors and corresponding Sondrestrom line-of-sight velocities and by comparing the end products of the instruments, the convection maps. All three comparisons showed overall reasonable agreement of the convection measurements though the data spread was significant and for some points a strong disagreement was obvious. Importantly, the convection map comparison showed a tendency for the SuperDARN velocities to be often less than the Sondrestrom drifts for strong flows (velocities > 1000 m/s) and larger for weak flows (velocities < 500 m/s). The second issue under investigation was the configuration of the ionospheric plasma convection and field-aligned currents (FACs) in the dayside ionosphere at small IMF B2 and By. By merging SuperDARN convection data for a number of events, it was found that convection tends to be compressed to the poleward edge of the polar cap with a noticeable decrease of the flow velociity inside the central polar cap for this condition. Also, for individual events, existence of three sheets of FACs was illustrated. FACs had similar appearance as region 1, region 2, and region 0 currents known from satellite magnetometer observations for the disturbed magnetosphere. Spatially, sheets of region 1 FACs were co-located with a line separating the plasma flow of

  3. A Review of the Efficacy and Safety of Litramine IQP-G-002AS, an Opuntia ficus-indica Derived Fiber for Weight Management

    PubMed Central

    Gruenwald, Joerg; Uebelhack, Ralf

    2014-01-01

    Sedentary lifestyle and caloric overconsumption are the key determinants of the escalating obesity prevalence. Reducing dietary fat absorption may help to induce a negative energy balance and thus help in managing weight problem. Apart from approved drug therapies, weight problems may also be aided with alternative and natural treatments. This paper compiled and reviewed the efficacy and safety of Litramine IQP-G-002AS, an Opuntia ficus-indica (OFI) derived fiber, in reducing dietary fat absorption and promoting weight loss. Evidence reviewed shows that Litramine IQP-G-002AS displays efficacy in promoting fat excretion and weight loss in four randomized, placebo-controlled clinical studies (including an unpublished pilot study). With a daily dosage of 3 g over a seven-day period, Litramine IQP-G-002AS showed an increased faecal fat excretion compared with placebo (15.8% (SD 5.8%) versus 4.6% (SD 3.1%); P < 0.001). In a 12-week study, significant greater weight loss (3.8 kg (SD 1.8 kg) versus 1.4 kg (SD 2.6 kg); P < 0.001) was observed in overweight and obese subjects treated with Litramine IQP-G-002AS as compared to placebo. No relevant gastrointestinal side effects have been reported for Litramine IQP-G-002AS at the dosages studied. PMID:25254061

  4. A Review of the Efficacy and Safety of Litramine IQP-G-002AS, an Opuntia ficus-indica Derived Fiber for Weight Management.

    PubMed

    Chong, Pee-Win; Lau, Kai-Zhia; Gruenwald, Joerg; Uebelhack, Ralf

    2014-01-01

    Sedentary lifestyle and caloric overconsumption are the key determinants of the escalating obesity prevalence. Reducing dietary fat absorption may help to induce a negative energy balance and thus help in managing weight problem. Apart from approved drug therapies, weight problems may also be aided with alternative and natural treatments. This paper compiled and reviewed the efficacy and safety of Litramine IQP-G-002AS, an Opuntia ficus-indica (OFI) derived fiber, in reducing dietary fat absorption and promoting weight loss. Evidence reviewed shows that Litramine IQP-G-002AS displays efficacy in promoting fat excretion and weight loss in four randomized, placebo-controlled clinical studies (including an unpublished pilot study). With a daily dosage of 3 g over a seven-day period, Litramine IQP-G-002AS showed an increased faecal fat excretion compared with placebo (15.8% (SD 5.8%) versus 4.6% (SD 3.1%); P < 0.001). In a 12-week study, significant greater weight loss (3.8 kg (SD 1.8 kg) versus 1.4 kg (SD 2.6 kg); P < 0.001) was observed in overweight and obese subjects treated with Litramine IQP-G-002AS as compared to placebo. No relevant gastrointestinal side effects have been reported for Litramine IQP-G-002AS at the dosages studied. PMID:25254061

  5. A new strategy for the synthesis of taurine derivatives using the 'safety-catch' principle for the protection of sulfonic acids.

    PubMed

    Seeberger, Sonja; Griffin, Roger J; Hardcastle, Ian R; Golding, Bernard T

    2007-01-01

    The safety-catch principle has been applied for the development of a new method for protecting sulfonic acids. 2,2-Dimethylsuccinic acid was reduced to 2,2-dimethylbutane-1,4-diol, which was selectively silylated to give 4-(tert-butyldiphenylsilanyloxy)-2,2-dimethylbutan-1-ol. Reaction of the latter compound with 2-chloroethanesulfonyl chloride in the presence of triethylamine afforded 4-(tert-butyldiphenylsilyloxy)-2,2-dimethylbutyl ethenesulfonate directly. The ethenesulfonate underwent Michael-type addition with secondary amines to give protected derivatives of taurine (2-aminoethanesulfonic acid). Deprotection was achieved on treatment with tetrabutylammonium fluoride, whereby cleavage of the silicon-oxygen bond led to an intermediate alkoxide that immediately cyclised to 2,2-dimethyltetrahydrofuran with liberation of a sulfonate. Pure sulfonic acids were obtained from the crude product by ion exchange chromatography on a strongly basic resin, which was eluted with aqueous acetic acid. The method developed should be generally applicable to the protection of sulfonic acids and is amenable to a multiparallel format. PMID:17164917

  6. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol.

    PubMed

    Arabi, Yaseen; Balkhy, Hanan; Hajeer, Ali H; Bouchama, Abderrezak; Hayden, Frederick G; Al-Omari, Awad; Al-Hameed, Fahad M; Taha, Yusri; Shindo, Nahoko; Whitehead, John; Merson, Laura; AlJohani, Sameera; Al-Khairy, Khalid; Carson, Gail; Luke, Thomas C; Hensley, Lisa; Al-Dawood, Abdulaziz; Al-Qahtani, Saad; Modjarrad, Kayvon; Sadat, Musharaf; Rohde, Gernot; Leport, Catherine; Fowler, Robert

    2015-01-01

    As of September 30, 2015, a total of 1589 laboratory-confirmed cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization (WHO). At present there is no effective specific therapy against MERS-CoV. The use of convalescent plasma (CP) has been suggested as a potential therapy based on existing evidence from other viral infections. We aim to study the feasibility of CP therapy as well as its safety and clinical and laboratory effects in critically ill patients with MERS-CoV infection. We will also examine the pharmacokinetics of the MERS-CoV antibody response and viral load over the course of MERS-CoV infection. This study will inform a future randomized controlled trial that will examine the efficacy of CP therapy for MERS-CoV infection. In the CP collection phase, potential donors will be tested by the enzyme linked immunosorbent assay (ELISA) and the indirect fluorescent antibody (IFA) techniques for the presence of anti-MERS-CoV antibodies. Subjects with anti-MERS-CoV IFA titer of ≥1:160 and no clinical or laboratory evidence of MERS-CoV infection will be screened for eligibility for plasma donation according to standard donation criteria. In the CP therapy phase, 20 consecutive critically ill patients admitted to intensive care unit with laboratory-confirmed MERS-CoV infection will be enrolled and each will receive 2 units of CP. Post enrollment, patients will be followed for clinical and laboratory outcomes that include anti-MERS-CoV antibodies and viral load. This protocol was developed collaboratively by King Abdullah International Medical Research Center (KAIMRC), Gulf Cooperation Council (GCC) Infection Control Center Group and the World Health Organization-International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO) MERS-CoV Working Group. It was approved in June 2014 by the Ministry of the National Guard Health Affairs Institutional Review Board (IRB

  7. Simultaneous determination of methocarbamol and Ibuprofen by first derivative synchronous fluorescence spectroscopic method in their binary mixture and spiked human plasma.

    PubMed

    Abdelwahab, Nada S; Abdelrahman, Maha M

    2014-01-01

    Methocarbamol is formulated with Ibuprofen for treatment of alleviated pain associated with muscle spasm. This manuscript describes a sensitive and selective first derivative synchronous spectrofluorimetric method for simultaneous determination of both drugs. Factors affecting method selectivity were studied where best results were obtained upon using Δ λ = 20 and water as a solvent. Methocartbamol was determined at 283 nm while Ibuprofen at 285.5 nm in the concentration ranges of 0.4-5 and 0.2-4.8 μg/mL, respectively. The applicability of the proposed method was ascertained by application to different laboratory prepared mixtures and marketed formulation. The high sensitivity achieved by the proposed method permitted its application for determination of the drugs in human plasma spiked with pure drugs and their combined tablets. The proposed method showed no significant difference when compared with the reported HPLC method using student's t-test and F-ratio test. PMID:23912962

  8. Optimum Conditions for the Efficacy and Safety of Cryofiltration Apheresis: An Analysis of Circuit Temperatures Depending on Plasma Flow Rate and Cooling Coil Lengths/Turns.

    PubMed

    Nakajima, Hirofumi; Kaneko, Shuzo; Sato, Yukihiro; Takano, Tomoo; Hosino, Toshihisa

    2015-08-01

    A system providing both appropriate cooling and warming are needed for the efficacy and safety of cryofiltration (CF) plasmapheresis. We measured some points of CF circuit temperatures with varying plasma flow rates (QP  = 10-40 mL/min) and the numbers of connecting cooling coils (one or two) under the conditions of blood flow rate (QB ) 100 mL/min with 7700-mm coil length, 19 turns, and 50-mL priming volume. We measured the respective temperatures of each point of starting/returning for an extracorporeal circuit (TA /TV ), intracooling coil (TC ), and post-plasma fractionator (PF) (TPF ). The subtraction of TV from TA (ΔT) was used as an indicator of safe return. There were no significant differences in TC , TPF , or ΔT in accordance with each QP between that of one and two coils. All of the Tc values under the condition QP  ≤ 20 mL/min achieved <4°C. The TPF under the condition QP  ≥ 20 mL/min was not significantly different compared to that of QP 30 mL/min (the lowest condition). Although the ΔT increased depending on the QP increase, the ΔT under the condition QP  ≤ 15 mL/min was not significantly different from that of the control (one-way double-filtration plasmapheresis [DFPP]) group. We conclude that (i) one coil is enough for effective cooling in CF, and (ii) an ideal QP that fulfills the required conditions for both effective cooling and sufficient warming of returning fluid does not exist, but QP from 15 to 20 mL/min may be a relevant range. PMID:26386219

  9. Effect of plasma-rich in platelet-derived growth factors on peri-implant bone healing: An experimental study in canines

    PubMed Central

    Birang, Reza; Torabi, Alireza; Shahabooei, Mohammad; Rismanchian, Mansour

    2012-01-01

    Background: Tissue engineering principles can be exploited to enhance alveolar and peri-implant bone reconstruction by applying such biological factors as platelet-derived growth factors. The objective of the present study is to investigate the effect of autologous plasma-rich in growth factors (on the healing of peri-implant bone in canine mandible). Materials and Methods: In this prospective experimental animal study, two healthy canines of the Iranian mix breed were selected. Three months after removing their premolar teeth on both sides of the mandible, 12 implants of the Osteo Implant Corporationsystem, 5 mm in diameter and 10 mm in length, were selected to be implanted. Plasma rich in growth factors (PRGF) were applied on six implants while the other six were used as plain implants without the plasma. The implants were installed in osteotomy sites on both sides of the mandible to be removed after 4 weeks with the surrounding bones using a trephine bur. Mesio-distal sections and implant blocks, 50 μ in diameter containing the peri-implant bone, were prepared By basic fuchin toluidine-bluefor histological and histomorphometric evaluation by optical microscope. The data were analyzed using Mann-Whitney Test (P<0.05). Results: The bone trabeculae and the type of bone generation in PRGF and control groups had no statistically significant differences (P=0.261, P=0.2) although the parameters showed higher measured values in the PRGF group. However, compared to the control, application of PRGF had significantly increased bone-to-implant contact (P=0.028) Conclusion: Based on the results, it may be concluded that application of PRGF on the surface of implant may enhance bone-to-implant contact. PMID:22363370

  10. The Effect of Recombinant Erythropoietin on Plasma Brain Derived Neurotrophic Factor Levels in Patients with Affective Disorders: A Randomised Controlled Study

    PubMed Central

    Vinberg, Maj; Miskowiak, Kamilla; Hoejman, Pernille; Pedersen, Maria; Kessing, Lars Vedel

    2015-01-01

    The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO) on plasma brain derived neurotrophic factor (BDNF) levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ≤ 14) (study 2). In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU) or saline (0.9% NaCl) infusions in a double-blind, placebo-controlled, parallel—group design. Plasma BDNF levels were measured at baseline and at weeks 5, 9 and at follow up, week 14. In contrast with our hypothesis, EPO down regulated plasma BDNF levels in patients with TRD (mean reduction at week 9 (95% CI): EPO 10.94 ng/l (4.51-21.41 ng/l); mean increase at week 9: Saline 0.52 ng/l, p=0.04 (-5.88-4.48 ng/l) p=0.04, partial ŋ2=0.12). No significant effects were found on BDNF levels in partially remitted patients with BD (p=0.35). The present effects of EPO on BDNF levels in patients with TRD point to a role of neurotrophic factors in the potential effects of EPO seen in TRD and BD. The neurobiological mechanisms underlying these effects and the interaction between EPO and peripheral levels on BDNF need to be further elucidated in human studies including a broad range of biomarkers. Trial Registration ClinicalTrials.gov: NCT00916552. PMID:26011424

  11. Plasma Surface Modification of Polyhedral Oligomeric Silsequioxane-Poly(carbonate-urea) Urethane with Allylamine Enhances the Response and Osteogenic Differentiation of Adipose-Derived Stem Cells.

    PubMed

    Chaves, Camilo; Alshomer, Feras; Palgrave, Robert G; Kalaskar, Deepak M

    2016-07-27

    This study present amino functionalization of biocompatible polymer polyhedral oligomeric silsequioxane-poly(carbonate-urea) urethane (POSS-PCU) using plasma polymerization process to induce osteogenic differentiation of adipose derived stem cells (ADSCs). Optimization of plasma polymerization process was carried out keeping cell culture application in mind. Thus, samples were rigorously tested for retention of amino groups under both dry and wet conditions. Physio-chemical characterization was carried out using ninhydrin test, X-ray photon spectroscopy, scanning electron microscopy, and static water contact analysis. Results from physio chemical characterization shows that functionalization of the amino group is not stable under wet conditions and optimization of plasma process is required for stable bonding of amino groups to the POSS-PCU polymer. Optimized samples were later tested in vitro in short and long-term culture to study differentiation of ADSCs on amino modified samples. Short-term cell culture shows that initial cell attachment was significantly (p < 0.001) improved on amine modified samples (NH2-POSS-PCU) compared to unmodified POSS-PCU. NH2-POSS-PCU samples also facilitates osteogenic differentiation of ADSCs as confirmed by immunological staining of cells for extracellular markers such as collagen Type I and osteopontin. Quantification of total collagen and ALP activity also shows significant (p < 0.001) increase on NH2-POSS-PCU samples compared to unmodified POSS-PCU. A pilot study also confirms that these optimized amino modified POSS-PCU samples can further be functionalized using bone inducing peptide such as KRSR using conventional wet chemistry. This further provides an opportunity for biofunctionalization of the polymer for various tissue specific applications. PMID:27384590

  12. Characterization of a 60-kDa Thermally Stable Antigenic Protein as a Marker for the Immunodetection of Bovine Plasma-Derived Food Ingredients.

    PubMed

    Ofori, Jack A; Hsieh, Yun-Hwa P

    2015-08-01

    A sandwich enzyme-linked immunosorbent assay (sELISA) based on 2 monoclonal antibodies (Bb3D6 and Bb6G12) that recognize a 60-kDa antigenic protein in bovine blood was previously developed for detecting bovine blood in animal feed for the prevention of mad cow disease. This study sought to establish the identity of this 60-kDa antigenic protein and consequently determine the suitability of the sELISA for detecting bovine plasma-derived food ingredients (BPFIs), which are widely used in dietary products without explicit labeling. Results from western blot confirmed the 60-kDa protein to be present in the plasma fraction of bovine blood. Further proteomic analyses involving 2-dimensional gel electrophoresis (2-D GE) and amino acid sequencing revealed the 60-kDa protein to be bovine serum albumin (BSA). The sELISA proved capable of detecting BPFIs in all the commercial dietary supplements tested, including those that were formulated with hydrolyzed BPFIs. The assay could also detect 0.01% and 0.5% of different BPFIs in spiked raw and cooked ground beef, respectively. This assay based on the detection of BSA therefore has the potential to become a valuable analytical tool to protect consumers who avoid consuming BPFIs for religious, health, or ethical reasons. PMID:26172875

  13. Effect of polyethylene glycol conjugation on the circulatory stability of plasma-derived human butyrylcholinesterase in mice.

    PubMed

    Sun, Wei; Luo, Chunyuan; Tipparaju, Prasanthi; Doctor, Bhupendra P; Saxena, Ashima

    2013-03-25

    Exogenously administered human serum butyrylcholinesterase (Hu BChE) was demonstrated to function as a bioscavenger of highly toxic organophosphorus (OP) compounds in several animal species. Since the enzyme is isolated from human serum, it is currently the most suitable pretreatment for human use. A dose of 200-300 mg/70 kg human adult is projected to provide protection from 2 X LD(50) of soman. Due to the limited supply of Hu BChE, strategies aimed at reducing the dose of enzyme are being explored. In this study, we investigated the effect of modification with polyethylene glycol (PEG) on the in vivo stability of Hu BChE. Mice were given two injections of either Hu BChE or Hu BChE modified with PEG-5K or PEG-20K, six weeks apart. Pharmacokinetic parameters, such as mean residence time (MRT), maximal concentration (C(max)), elimination half-life (T(1/2)), and area under the plasma concentration time curve extrapolated to infinity (AUC), were determined. For the first injection, values for MRT, T(1/2), Cmax, and AUC for PEG-5K-Hu BChE and PEG-20K-Hu BChE were similar to those for Hu BChE. These values for the second injection of Hu BChE as well as PEG-Hu BChEs were lower as compared to those for the first injections, likely due to antibody-mediated clearance. PMID:23220586

  14. Research on dye wastewater decoloration by pulse discharge plasma combined with charcoal derived from spent tea leaves.

    PubMed

    Wang, Tiecheng; Qu, Guangzhou; Pei, Shuzhao; Liang, Dongli; Hu, Shibin

    2016-07-01

    Pulsed discharge plasma (PDP) combined with charcoal (PDP-charcoal) was employed to treat dye wastewater, with methyl orange (MO) as the model pollutant. The charcoal was prepared using spent tea leaves and was characterized by scanning electron microscopy, Fourier-transform infrared spectroscopy, and Boehm titration to investigate the adsorption and catalytic characteristics before and after adsorption and PDP treatment. The prepared charcoal exhibited a high MO adsorption capacity, and the adsorption process followed the pseudo-second-order kinetic model and the Freundlich model. The MO decoloration efficiency reached 69.8 % within 7.5 min of treatment in the PDP-charcoal system, whereas values of 29.2 and 25.9 % were achieved in individual PDP and charcoal systems, respectively. The addition of n-butanol and H2PO4 (-) presented inhibitive effects on MO decoloration in the PDP system. However, these effects were much weaker in the PDP-charcoal system. In addition, the effects of charcoal on O3 and H2O2 formation were evaluated, and the results showed that both the O3 and H2O2 concentrations decreased in the presence of charcoal. The MO decomposition intermediates were analyzed using UV-Vis spectrometry and GC-MS. 1,4-Benzoquinone, 4-nitrophenol, 4-hydroxyaniline, and N,N'-dimethylaniline were detected. A possible pathway for MO decomposition in this system was proposed. PMID:27026548

  15. Simultaneous determination of desloratadine and montelukast sodium using second-derivative synchronous fluorescence spectrometry enhanced by an organized medium with applications to tablets and human plasma.

    PubMed

    Ibrahim, F A; El-Enany, N; El-Shaheny, R N; Mikhail, I E

    2015-06-01

    A rapid, simple, and sensitive second-derivative synchronous fluorimetric method has been developed and validated for the simultaneous analysis of a binary mixture of desloratadine (DSL) and montelukast sodium (MKT) in their co-formulated tablets. The method is based on measurement of the synchronous fluorescence intensities of the two drugs in McIlvaine's buffer, pH 2.3, in the presence of carboxy methyl cellulose sodium (CMC) as a fluorescence enhancer at a constant wavelength difference (Δλ) of 160 nm. The presence of CMC enhanced the synchronous fluorescence intensity of DSL by 216% and that of MKT by 28%. A linear dependence of the concentration on the amplitude of the second derivative synchronous fluorescence spectra was achieved over the ranges of 0.10-2.00 and 0.20-2.00 µg/mL with limits of detection of 0.02 and 0.03, and limits of quantification of 0.05 and 0.10 µg/mL for DSL and MKT, respectively. The proposed method was successfully applied for the determination of the studied compounds in laboratory-prepared mixtures and tablets. The results were in good agreement with those obtained with the comparison method. The high sensitivity attained by the proposed method allowed the determination of MKT in spiked human plasma with average % recovery of 100.11 ± 2.44 (n = 3). PMID:25209552

  16. Safety and immunogenicity in man of a cell culture derived trivalent live attenuated seasonal influenza vaccine: a Phase I dose escalating study in healthy volunteers.

    PubMed

    Heldens, Jacco; Hulskotte, Ellen; Voeten, Theo; Breedveld, Belinda; Verweij, Pierre; van Duijnhoven, Wilbert; Rudenko, Larissa; van Damme, Pierre; van den Bosch, Han

    2014-09-01

    Live attenuated influenza vaccine (LAIV) offers the promise of inducing a variety of immune responses thereby conferring protection to circulating field strains. LAIVs are based on cold adapted and temperature sensitive phenotypes of master donor viruses (MDVs) containing the surface glycoprotein genes of seasonal influenza strains. Two types of MDV lineages have been described, the Ann Arbor lineages and the A/Leningrad/17 and B/USSR/60 lineages. Here the safety and immunogenicity of a Madin Darby Canine Kidney - cell culture based, intranasal LAIV derived from A/Leningrad/17 and B/USSR, was evaluated in healthy influenza non-naive volunteers 18-50 years of age. In a double-blind, randomized, placebo-controlled design, single escalating doses of 1×10(5), 1×10(6), or 1×10(7) tissue culture infectious dose 50% (TCID50) of vaccine containing each of the three influenza virus re-assortants recommended by the World Health Organization for the 2008-2009 season were administered intranasally. A statistically significant geometric mean increase in hemagglutination inhibition titer was reached for influenza strain A/H3N2 after immunization with all doses of LAIV. For the A/H1N1 and B strains, the GMI in HI titer did not increase for any of the doses. Virus neutralization antibody titers showed a similar response pattern. A dose-response effect could not be demonstrated for any of the strains, neither for the HI antibody nor for the VN antibody responses. No influenza like symptoms, no nasal congestions, no rhinorrhea, or other influenza related upper respiratory tract symptoms were observed. In addition, no difference in the incidence or nature of adverse events was found between vaccine and placebo treated subjects. Overall, the results indicated that the LAIV for nasal administration is immunogenic (i.e. able to provoke an immune response) and safe both from the perspective of the attenuated virus and the MDCK cell line from which it was derived, and it warrants

  17. Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs with inflammatory bowel disease: Clinical and laboratory outcomes.

    PubMed

    Pérez-Merino, E M; Usón-Casaús, J M; Zaragoza-Bayle, C; Duque-Carrasco, J; Mariñas-Pardo, L; Hermida-Prieto, M; Barrera-Chacón, R; Gualtieri, M

    2015-12-01

    Mesenchymal stem cells (MSCs) have shown immunomodulatory and anti-inflammatory effects in experimental colitis, and promising clinical results have been obtained in humans with Crohn's disease and ulcerative colitis. The aim of this study was to determine the safety and feasibility of adipose tissue-derived MSC (ASC) therapy in dogs with inflammatory bowel disease (IBD). Eleven dogs with confirmed IBD received one ASC intravascular (IV) infusion (2 × 10(6) cells/kg bodyweight). The outcome measures were clinical response based on percentage reduction of the validated Clinical Inflammatory Bowel Disease Activity Index (CIBDAI) and Canine Chronic Enteropathy Clinical Activity Index (CCECAI), as well as normalisation of C-reactive protein (CRP), albumin, folate and cobalamin serum concentrations at day 42 post-treatment. The Wilcoxon test was used to compare variables before and after treatment. No acute reaction to ASC infusion and no side effects were reported during follow-up in any dog. Six weeks post-treatment, the CIBDAI and CCECAI decreased significantly and albumin, cobalamin and folate concentrations increased substantially. Differences in CRP concentrations pre- and post-treatment were not significant (P = 0.050). Clinical remission (defined by a reduction of initial CIBDAI and CCECAI >75%) occurred in 9/11 dogs at day 42. The two remaining dogs showed a partial response with reduction percentages of 69.2% and 71.4%. In conclusion, a single IV infusion of allogeneic ASCs was well tolerated and appeared to produce clinical benefits in dogs with severe IBD. PMID:26526522

  18. Long-Term (Postnatal Day 70) Outcome and Safety of Intratracheal Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Neonatal Hyperoxic Lung Injury

    PubMed Central

    Ahn, So Yoon; Chang, Yun Sil; Kim, Soo Yoon; Sung, Dong Kyung; Kim, Eun Sun; Rime, So Yub; Yu, Wook Joon; Choi, Soo Jin; Oh, Won Il

    2013-01-01

    Purpose This study was performed to evaluate the long-term effects and safety of intratracheal (IT) transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in neonatal hyperoxic lung injury at postnatal day (P)70 in a rat model. Materials and Methods Newborn Sprague Dawley rat pups were subjected to 14 days of hyperoxia (90% oxygen) within 10 hours after birth and allowed to recover at room air until sacrificed at P70. In the transplantation groups, hUCB-MSCs (5×105) were administered intratracheally at P5. At P70, various organs including the heart, lung, liver, and spleen were histologically examined, and the harvested lungs were assessed for morphometric analyses of alveolarization. ED-1, von Willebrand factor, and human-specific nuclear mitotic apparatus protein (NuMA) staining in the lungs and the hematologic profile of blood were evaluated. Results Impaired alveolar and vascular growth, which evidenced by an increased mean linear intercept and decreased amount of von Willebrand factor, respectively, and the hyperoxia-induced inflammatory responses, as evidenced by inflammatory foci and ED-1 positive alveolar macrophages, were attenuated in the P70 rat lungs by IT transplantation of hUCB-MSCs. Although rare, donor cells with human specific NuMA staining were persistently present in the P70 rat lungs. There were no gross or microscopic abnormal findings in the heart, liver, or spleen, related to the MSCs transplantation. Conclusion The protective and beneficial effects of IT transplantation of hUCB-MSCs in neonatal hyperoxic lung injuries were sustained for a prolonged recovery period without any long-term adverse effects up to P70. PMID:23364976

  19. PAF-degrading acetylhydrolase is preferentially associated with dense LDL and VHDL-1 in human plasma. Catalytic characteristics and relation to the monocyte-derived enzyme.

    PubMed

    Tselepis, A D; Dentan, C; Karabina, S A; Chapman, M J; Ninio, E

    1995-10-01

    In human plasma, platelet activating factor (PAF)-degrading acetylhydrolase (acetylhydrolase) is principally transported in association with LDLs and HDLs; this enzyme hydrolyzes PAF and short-chain forms of oxidized phosphatidylcholine, transforming them into lyso-PAF and lysophosphatidylcholine, respectively. We have examined the distribution, catalytic characteristics, and transfer of acetylhydrolase activity among plasma lipoprotein subspecies separated by isopycnic density gradient ultracentrifugation; the possibility that the plasma enzyme may be partially derived from adherent monocytes has also been evaluated. In normolipidemic subjects with Lp(a) levels < 0.1 mg/mL, acetylhydrolase was associated preferentially with small, dense LDL particles (LDL-5; d = 1.050 to 1.063 g/mL) and with the very-high-density lipoprotein-1 subfraction (VHDL-1; d = 1.156 to 1.179 g/mL), representing 23.9 +/- 1.7% and 20.6 +/- 3.2%, respectively, of total plasma activity. The apparent Km values for PAF of the enzyme associated with such lipoproteins were 89.7 +/- 23.4 and 34.8 +/- 4.5 mumol/L for LDL-5 and VHDL-1, respectively: indeed, the Km value for LDL-5 was some 10-fold higher than that of the light LDL-1, LDL-2, and LDL-3 subspecies, whereas the Km of VHDL-1 was some twofold greater than those of the HDL-2 and HDL-3 subspecies. Furthermore, when expressed on the basis of unit plasma volume, the Vmax of the acetylhydrolase associated with LDL-5 was some 150-fold greater than that in LDL-1 (d = 1.019 to 1.023 g/mL). No significant differences in the pH dependence of enzyme activity or in sensitivity to protease inactivation, sulfydryl reagents, the serine protease inhibitor Pefabloc, or the PAF antagonist CV 3988 could be detected between apo B-containing and apo A-I-containing lipoprotein particle subspecies. Incubation of LDL-1 (Km = 8.4 +/- 2.6 mumol/L) and LDL-2 (d = 1.023 to 1.029 g/mL; Km = 8.4 +/- 3.3 mumol/L) subspecies with LDL-5, in which acetylhydrolase had been

  20. Batch recall of French plasma-derived products due to variant Creutzfeldt-Jakob disease risk: the psychological impact on haemophilic patients, changes in their therapeutic demands and behaviour and ethical considerations.

    PubMed

    Aouba, A; Harroche, A; Frenzel, L; Torchet, M-F; Rothschild, C; François, I; Mamzer-Bruneel, M-F

    2015-01-01

    The choice of plasma-derived products (PdP) vs. recombinant products (RP) for treating haemophilia is influenced by the infectious and perceived safety of the products. Batch recall of PdP due to the risk of variant Creutzfeldt-Jakob disease (vCJD) may have unfavourable psychological impacts on haemophilia patients and influence their product preferences. This study aimed to assess the psychological impact of batch recalls of PdP in six haemophilia patients and their therapeutic demands, and to discuss the ethical problems in physicians' management of this event. A survey was conducted using a new interview form and an existing anxiety and depression questionnaire. Batch recalls produce recurrent negative emotional outcomes in haemophiliacs and their families. The quality, understanding and efficiency of the batch recall announcements were unsatisfactory in some respects. Only one patient still had some of the vials in question, and only three patients understood the real reason for the batch recall. Four patients asked to change their PdP for RP; a fifth patient was considering doing so. Here, topics for discussion include the delivery of an unclear message to patients about a very uncertain risk of a frightening disease, the reasons to maintain PdP when RP are largely available, except in specific cases, and the related discomfort for caregivers. The ethical questions revealed by batch recalls and the high psychological impact of vCJD risk on patients can no longer be ignored, and require surveys assessing the rationales and choices of the healthcare authorities, manufacturers, prescribers and users. PMID:25545300

  1. Interactions between the plasma membrane and the antimicrobial peptide HP (2-20) and its analogues derived from Helicobacter pylori

    PubMed Central

    Lee, Kwang H.; Lee, Dong G.; Park, Yoonkyung; Kang, Dong-Il; Shin, Song Y.; Hahm, Kyung-Soo; Kim, Yangmee

    2005-01-01

    HP (2-20), a 19-residue peptide derived from the N-terminus of Helicobacter pylori ribosomal protein L1, has antimicrobial activity but is not cytotoxic to human erythrocytes. We synthesized several peptide analogues to investigate the effects of substitutions on structure and antimicrobial activity. Replacement of Gln16 and Asp18 with tryptophan [anal-3 (analogue-3)] caused a dramatic increase in lytic activities against bacteria and fungi. By contrast, a decrease in amphiphilicity caused by replacement of Phe5 or Leu11 with serine was accompanied by a reduction in antimicrobial activity. Analysis of the tertiary structures of the peptides in SDS micelles by NMR spectroscopy revealed that they have a well-defined α-helical structure. Among the analogues, anal-3 has the longest α-helix, from Val4 to Trp18. The enhanced hydrophobicity and increased α-helicity results in enhanced antimicrobial activity in anal-3 without an increase in haemolytic activity. Fluorescence experiments proved that the bacterial-cell selectivity of the anal-3 peptide is due to its high binding affinity for negatively charged phospholipids in bacterial cells. Results showing the effect of spin-labels on the NMR spectra indicated that the side chains in the hydrophobic phase of the amphiphilic α-helix are buried on the surface of the micelle and the tryptophan indole ring is anchored in the membrane surface. Because anal-3 shows high selectivity towards bacterial and fungal cells, it may provide an avenue for the development of new antibiotics. PMID:16255716

  2. Electrocardiogram Derived QRS Duration >120 ms is Associated With Elevated Plasma Homocysteine Levels in a Rural Australian Cross-Sectional Population

    PubMed Central

    Leng, Yvonne Lee Yin; Zhou, Yuling; Ke, Honghong; Jelinek, Herbert; McCabe, Joel; Assareh, Hassan; McLachlan, Craig S.

    2015-01-01

    Abstract Homocysteine levels in the low to moderate range for cardiovascular risk have been previously associated with left ventricular cardiac hypertrophy (LVH). Electrocardiogram (ECG) derived QRS duration has also been used as an epidemiological screening marker for cardiac hypertrophy risk. QRS duration cut offs have not been previously modeled to assess homocysteine levels in community populations. Our aims are to determine if QRS duration is associated with an elevated homocysteine level in a cross-sectional Australian aging rural population. A retrospective study design utilizing a rural health diabetic screening clinic database containing observational data from the period January 9, 2002 till September 25, 2012. One hundred seventy-eight individuals (>21 years of age) from the database were included in the study. Inclusion criteria included being nondiabetic and having both a QRS duration measure and a matching homocysteine level within the same subject. All participants were from the Albury-Wodonga area, with a mean age of >64 years for both sexes. Mean population homocysteine plasma levels were 10.4 μmol/L (SD = 3.6). The mean QRS duration was 101.8 ms (SD = 17.4). Groups were stratified on the basis of QRS duration (≤120 ms [n = 157] and >120 ms [n = 21]). QRS duration subgroup (≤120 ms vs >120 ms) mean differences across homocysteine levels were 10.1 μmol/L (SD = 3.3) and 12.2 μmol/L (SD = 4.7), respectively (P = 0.016). Other ECG parameters (PQ interval, QTc interval, and QT dispersion) measurements were not significantly associated with differences in plasma homocysteine (P = not significant). We conclude that in community populations homocysteine may be moderately elevated when QRS durations are >120 ms. Small additional increases in homocysteine levels may suggest a risk factor for ECG diagnosis of LVH. PMID:26166085

  3. [Viral safety of biological medicinal products].

    PubMed

    Stühler, A; Blümel, J

    2014-10-01

    Viral safety of blood donations, plasma products, viral vaccines and gene therapy medicinal products, biotechnical-derived products and tissue and cell therapy products is a particular challenge. These products are manufactured using a variety of human or animal-derived starting materials and reagents; therefore, extensive testing of donors and of cell banks established for production is required. Furthermore, the viral safety of reagents, such as bovine sera, porcine trypsin and human transferrin or albumin needs to be considered. Whenever possible, manufacturing steps for inactivation or removal of viruses should be introduced; however, sometimes it is not possible to introduce such steps for tissues or cell-based medicinal products as the activity and viability of cells will be compromised. It might be possible to implement steps for inactivation or removal of potential contaminating enveloped viruses only for production of small and stable non-enveloped viral gene vectors. PMID:25123140

  4. Safety analysts training

    SciTech Connect

    Bolton, P.

    2000-10-01

    The purpose of this task was to support ESH-3 in providing Airborne Release Fraction and Respirable Fraction training to safety analysts at LANL who perform accident analysis, hazard analysis, safety analysis, and/or risk assessments at nuclear facilities. The task included preparation of materials for and the conduct of two 3-day training courses covering the following topics: safety analysis process; calculation model; aerosol physic concepts for safety analysis; and overview of empirically derived airborne release fractions and respirable fractions.

  5. Cinnamon extract regulates plasma levels of adipose-derived factors and expression of multiple genes related to carbohydrate metabolism and lipogenesis in adipose tissue of fructose-fed rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We reported previously that a dietary cinnamon extract (CE) improves systemic insulin sensitivity and dyslipidemia by enhancing insulin signaling. In the present study, we examined the effects of CE on several biomarkers including plasma levels of adipose-derived adipokines, and the potential molec...

  6. Sexually-Transmitted/Founder HIV-1 Cannot Be Directly Predicted from Plasma or PBMC-Derived Viral Quasispecies in the Transmitting Partner

    PubMed Central

    Frange, Pierre; Meyer, Laurence; Jung, Matthieu; Goujard, Cecile; Zucman, David; Abel, Sylvie; Hochedez, Patrick; Gousset, Marine; Gascuel, Olivier; Rouzioux, Christine; Chaix, Marie-Laure

    2013-01-01

    Objective Characterization of HIV-1 sequences in newly infected individuals is important for elucidating the mechanisms of viral sexual transmission. We report the identification of transmitted/founder viruses in eight pairs of HIV-1 sexually-infected patients enrolled at the time of primary infection (“recipients”) and their transmitting partners (“donors”). Methods Using a single genome-amplification approach, we compared quasispecies in donors and recipients on the basis of 316 and 376 C2V5 env sequences amplified from plasma viral RNA and PBMC-associated DNA, respectively. Results Both DNA and RNA sequences indicated very homogeneous viral populations in all recipients, suggesting transmission of a single variant, even in cases of recent sexually transmitted infections (STIs) in donors (n = 2) or recipients (n = 3). In all pairs, the transmitted/founder virus was derived from an infrequent variant population within the blood of the donor. The donor variant sequences most closely related to the recipient sequences were found in plasma samples in 3/8 cases and/or in PBMC samples in 6/8 cases. Although donors were exclusively (n = 4) or predominantly (n = 4) infected by CCR5-tropic (R5) strains, two recipients were infected with highly homogeneous CXCR4/dual-mixed-tropic (X4/DM) viral populations, identified in both DNA and RNA. The proportion of X4/DM quasispecies in donors was higher in cases of X4/DM than R5 HIV transmission (16.7–22.0% versus 0–2.6%), suggesting that X4/DM transmission may be associated with a threshold population of X4/DM circulating quasispecies in donors. Conclusions These suggest that a severe genetic bottleneck occurs during subtype B HIV-1 heterosexual and homosexual transmission. Sexually-transmitted/founder virus cannot be directly predicted by analysis of the donor’s quasispecies in plasma and/or PBMC. Additional studies are required to fully understand the traits that confer the capacity to transmit and

  7. Nuclear safety

    NASA Technical Reports Server (NTRS)

    Buden, D.

    1991-01-01

    Topics dealing with nuclear safety are addressed which include the following: general safety requirements; safety design requirements; terrestrial safety; SP-100 Flight System key safety requirements; potential mission accidents and hazards; key safety features; ground operations; launch operations; flight operations; disposal; safety concerns; licensing; the nuclear engine for rocket vehicle application (NERVA) design philosophy; the NERVA flight safety program; and the NERVA safety plan.

  8. Presence of chromogranin-derived antimicrobial peptides in plasma during coronary artery bypass surgery and evidence of an immune origin of these peptides.

    PubMed

    Tasiemski, Aurélie; Hammad, Hamida; Vandenbulcke, Franck; Breton, Christophe; Bilfinger, Thomas J; Pestel, Joel; Salzet, Michel

    2002-07-15

    Chromogranin A (CGA) and chromogranin B (CGB) are acidic proteins stored in secretory organelles of endocrine cells and neurons. In addition to their roles as helper proteins in the packaging of peptides, they may serve as prohormones to generate biologically active peptides such as vasostatin-1 and secretolytin. These molecules derived from CGA and CGB, respectively, possess antimicrobial properties. The present study demonstrates that plasmatic levels of both vasostatin-1 and secretolytin increase during surgery in patients undergoing cardiopulmonary bypass (CPB). Vasostatin-1 and secretolytin, initially present in plasma at low levels, are released just after skin incision. Consequently, they can be added to enkelytin, an antibacterial peptide derived from proenkephalin A, for the panoply of components acting as a first protective barrier against hypothetical invasion of pathogens, which may occur during surgery. CGA and CGB, more commonly viewed as markers for endocrine and neuronal cells, were also found to have an immune origin. RNA messengers coding for CGB were amplified by reverse transcription-polymerase chain reaction in human monocytes, and immunocytochemical analysis by confocal microscopy revealed the presence of CGA or CGB or both in monocytes and neutrophils. A combination of techniques including confocal microscopic analysis, mass spectrometry measurement, and antibacterial tests allowed for the identification of the positive role of interleukin 6 (IL-6) in the secretolytin release from monocytes in vitro. Because IL-6 release is known to be strongly enhanced during CPB, we suggest a possible relationship between IL-6 and the increased level of secretolytin in patients undergoing CPB. PMID:12091348

  9. Modulational instability, nonautonomous breathers and rogue waves for a variable-coefficient derivative nonlinear Schrödinger equation in the inhomogeneous plasmas

    SciTech Connect

    Wang, Lei Li, Min; Qi, Feng-Hua; Xu, Tao

    2015-03-15

    Under investigation in this paper is a variable-coefficient derivative nonlinear Schrödinger (vc-DNLS) equation modeling the nonlinear Alfvén waves in the inhomogeneous plasmas. The modulation instability is examined for this inhomogeneous nonlinear model. The nonautonomous breather and rogue wave solutions of the vc-DNLS equation are obtained via the modified Darboux transformation. It is found that the velocity and amplitude of the breather can be controlled by the inhomogeneous magnetic field and nonuniform density. Such novel phenomena as breather amplification and nonlinear Talbot effect-like property are demonstrated with the proper choices of the inhomogeneous parameters. Furthermore, dynamics of the fundamental rogue wave, periodical rogue wave, and composite rogue wave are graphically discussed. The trajectories and amplitudes of the rogue waves can be manipulated by the inhomogeneous magnetic field and nonuniform density. In addition, the nonlinear tunneling of the rogue waves and breathers is studied. As an application, a sample model is treated with our results, and the graphical illustrations exhibit the compressing, expanding, and fluctuating phenomena of the Alfvén rogue waves.

  10. Platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells: stimulatory effects on proliferation and migration of fibroblasts and keratinocytes in vitro.

    PubMed

    Stessuk, Talita; Puzzi, Maria Beatriz; Chaim, Elinton Adami; Alves, Paulo César Martins; de Paula, Erich Vinicius; Forte, Andresa; Izumizawa, Juliana Massae; Oliveira, Carolina Caliári; Frei, Fernando; Ribeiro-Paes, João Tadeu

    2016-09-01

    The clinical use of tissue engineering associated with cell therapy is considered a new alternative therapy for the repair of chronic lesions with potential application in different medical areas, mostly in orthopedic and dermatological diseases. Platelet-rich plasma (PRP) is a rich source of growth factors and cytokines important for wound healing. Adipose-derived mesenchymal stem cells (ADSCs) have shown potential to accelerate the resolution of ulcers, to stimulate cell proliferation, and to benefit the quality of skin repair. This study aims to determine the effect of PRP and conditioned medium (CM) from ADSC on fibroblast and keratinocyte proliferation in vitro. Migration and proliferation assays were performed to evaluate the growth of fibroblasts and keratinocytes in the presence of PRP, CM, and CM + PRP. Significant proliferative stimulation was observed after 48 h of culture (p < 0.05) on mean absorbance of fibroblasts cultured with 10 and 25 % PRP, 100 % CM, and 25 % PRP + 25 % CM, if compared with control. Keratinocyte proliferation was stimulated after 48 h in cultures with 25, 50, and 100 % CM, and growth was compared with controls. The migration assay detected a significant migratory stimulus in fibroblasts cultured with 10 % PRP + 10 % CM after 48 h. These in vitro results suggest that PRP and ADSC have therapeutic potential for healing and re-epithelialization of chronic wounds in vivo. PMID:27394438