scholarly journals Optimization of Heparin Monitoring with Anti-FXa Assays and the Impact of Dextran Sulfate for Measuring All Drug Activity

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 700
Author(s):  
Jean Amiral ◽  
Cédric Amiral ◽  
Claire Dunois
Keyword(s):  
Molecular Weight ◽  
Blood Circulation ◽  
Dextran Sulfate ◽  
Drug Dosage ◽  
International Standards ◽  
Low Molecular Weight ◽  
Key Factors ◽  
The One ◽  
The Impact ◽  
Assay Conditions

Heparins, unfractionated or low molecular weight, are permanently in the spotlight of both clinical indications and laboratory monitoring. An accurate drug dosage is necessary for an efficient and safe therapy. The one-stage kinetic anti-FXa assays are the most widely and universally used with full automation for large series, without needing exogenous antithrombin. The WHO International Standards are available for UFH and LMWH, but external quality assessment surveys still report a high inter-assay variability. This heterogeneity results from the following: assay formulation, designed without or with dextran sulfate to measure all heparin in blood circulation; calibrators for testing UFH or LMWH with the same curve; and automation parameters. In this study, various factors which impact heparin measurements are reviewed, and we share our experience to optimize assays for testing all heparin anticoagulant activities in plasma. Evidence is provided on the usefulness of low molecular weight dextran sulfate to completely mobilize all of the drug present in blood circulation. Other key factors concern the adjustment of assay conditions to obtain fully superimposable calibration curves for UFH and LMWH, calibrators’ formulations, and automation parameters. In this study, we illustrate the performances of different anti-FXa assays used for testing heparin on UFH or LMWH treated patients’ plasmas and obtained using citrate or CTAD anticoagulants. Comparable results are obtained only when the CTAD anticoagulant is used. Using citrate as an anticoagulant, UFH is underestimated in the absence of dextran sulfate. Heparin calibrators, adjustment of automation parameters, and data treatment contribute to other smaller differences.

scholarly journals Optimization of Heparin Monitoring with Anti-FXa Assays and Impact of Dextran Sulfate for Measuring All In-Vivo Drug Activity

2021 ◽  
Author(s):  
JEAN AMIRAL ◽  
Cedric AMIRAL ◽  
Claire DUNOIS
Keyword(s):  
Molecular Weight ◽  
Blood Circulation ◽  
Dextran Sulfate ◽  
Drug Dosage ◽  
Low Molecular Weight ◽  
Key Factors ◽  
The One ◽  
Assay Conditions ◽  
Plasma Heparin

Heparins, Unfractionated or Low Molecular Weight, are permanently at the spotlight of both clinical indications and laboratory monitoring. An accurate drug dosage is necessary for an effi-cient and safe therapy. The one-stage anti-FXa kinetics’ assays are the most widely and universally used with full automation for large series, without needing exogenous Antithrombin. WHO in-ternational standards are available for UFH and LMWH, but external quality assessment surveys still report a high inter-assay variability. This heterogeneity results from: assay formulation, designed without or with dextran sulfate to measure all heparin in blood circulation; calibrators for testing UFH or LMWH with the same curve; and automation parameters. The various factors which impact heparin measurements are reviewed, and we share our experience to optimize assays for completely testing plasma heparin. Evidence is provided on the usefulness of low molecular weight dextran sulfate to mobilize all drug present in blood circulation. Other key factors concern adjustment of assay conditions to obtain fully superimposable calibration curves for UFH and LMWH, and automation parameters. The study is illustrated by the performances of the various anti-FXa assays used for testing heparin on UFH or LMWH treated patients’ plasmas and obtained using citrate or CTAD anticoagulants. Comparable results are obtained only when CTAD anti-coagulant is used. Using citrate UFH is underestimated in the absence of dextran sulfate. Heparin calibrators, adjustment of automation parameters and data treatment contribute to other smaller differences.

scholarly journals Laundering Black Money by Means of Offshore Zones: The Negative Impact and Ways to Resolve

2021 ◽  
Vol 8 (523) ◽  
pp. 140-150
Author(s):  
O. T. Zamaslo ◽  
◽  
D. A. Kozak ◽  
Keyword(s):  
National Economy ◽  
Tax Evasion ◽  
Negative Impact ◽  
Action Plan ◽  
International Standards ◽  
Key Factors ◽  
Profit Shifting ◽  
State Budget ◽  
Business Entities ◽  
The Impact

The article is aimed at examining the problem of laundering black money in the offshore jurisdictions. Attention is paid to the key factors that attract economic entities regarding business registration in offshore zones. The impact of the tax burden on the process of moving profits to offshore jurisdictions is considered. The volumes of losses of the State Budget of Ukraine related to tax evasion of the funds placed on the accounts of offshore companies have been studied. The most typical schemes of laundering black money in offshore zones are presented, as well as a number of stages that form the process of laundering are highlighted. Emphasis is placed on round tripping investment as a key mechanism for returning foreign funds to a resident in the form of foreign direct investment, the main factors in the use of round trip transactions by Ukrainian business entities are allocated. Attention is drawn to the percentage of countries, which are the largest investors in Ukraine. It is determined that the use of offshore schemes by Ukrainian businesses contributes to the growth of the shadowing of the national economy and causes a direct negative impact on Ukrainian financial security, which is confirmed by the results of the National Risk Assessment 2019. Emphasis is placed on the OECD / G20 Base Erosion and Profit Shifting (BEPS) initiative to prevent money laundering offshore, and Ukraine’s key measures to implement relevant international standards are specified. Prospects for further research in this direction are to identify measures directed towards deoffshorization of the national economy, including through the implementation of the BEPS 2.0 Action Plan.

scholarly journals Changes in Protein Composition in the Grain and Malt after Fusarium Infection Dependently of Wheat Resistance

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 112 ◽  
Author(s):  
Spanic ◽  
Horvat ◽  
Drezner ◽  
Zdunic
Keyword(s):  
Molecular Weight ◽  
Grain Yield ◽  
Susceptible Variety ◽  
Resistant Variety ◽  
Low Molecular Weight ◽  
Protein Distribution ◽  
Glutenin Subunits ◽  
Wheat Grains ◽  
Fusarium Infection ◽  
The Impact

The grain yield, as well as the quality and safety of the wheat grains and corresponding malt can be compromised by Fusarium spp. infection. The protein content of the grain affects the chemical composition and enzyme levels of the finished malt. The malting industry demands varieties with good malting and brewing performance, as well as good agronomic performance and disease resistance. The best method of disease control is breeding and selection for resistant varieties. Due to higher requirements for malting wheat worldwide, the goal of this investigation was to explore changes in protein distribution in wheat grains and corresponding malt, which are under higher pressure of Fusarium head blight (FHB) infestation in field conditions. The present study provides new knowledge on the impact of the FHB on the distribution of protein components of naturally Fusarium-infected (control) and Fusarium-inoculated wheat varieties in the grain and the corresponding malt in two consecutive years (2015/2016 and 2016/2017). The results showed that Fusarium infection of the susceptible variety Golubica, decreased total glutenins (5.9%), and both high and low molecular weight glutenin subunits (2.5% and 3.5%, respectively) in wheat grains, compared to control, in 2016. In contrast, gliadins and α-gliadins increased significantly (+7.6% and +5.1%, respectively) in the same variety. Wheat grains of the more resistant variety Vulkan showed an increase of the total glutenins content (+4.3%), and of high and of low molecular weight glutenin subunits (+1.2% and +3.2%, respectively) after Fusarium-inoculation, compared to naturally infected grains in 2016. Susceptible variety Golubica increased total glutenins (+9.1%), and both high and low molecular weight glutenin subunits (+3.5% and +5.6%, respectively) after Fusarium-inoculation in wheat malt, compared to naturally infected malt in 2016. In 2017, when disease pressure was higher than in 2016, there was a tendency in all varieties to increase gliadins and its sub fractions after malting, and to decrease glutenins and its sub fractions in Fusarium-inoculated treatment. In conclusion, FHB dramatically depressed grain yield (up to 37%) and quality (glutenins and high molecular weight subunits) in the susceptible Fusarium variety, which makes it inconvenient for malting.

scholarly journals Low-Molecular-Weight Dextran Sulfate Nanocapsules Inhibit the Adhesion of Helicobacter pylori to Gastric Cells

2019 ◽  
Vol 2 (11) ◽  
pp. 4777-4789 ◽  
Author(s):  
Bianca Menchicchi ◽  
Eleni Savvaidou ◽  
Christian Thöle ◽  
Andreas Hensel ◽  
Francisco M. Goycoolea
Keyword(s):  
Molecular Weight ◽  
Helicobacter Pylori ◽  
Dextran Sulfate ◽  
Low Molecular Weight ◽  
Gastric Cells

scholarly journals Low Molecular Weight Procyanidins from Grape Seeds Enhance the Impact of 5-Fluorouracil Chemotherapy on Caco-2 Human Colon Cancer Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e98921 ◽  
Author(s):  
Ker Y. Cheah ◽  
Gordon S. Howarth ◽  
Keren A. Bindon ◽  
James A. Kennedy ◽  
Susan E. P. Bastian
Keyword(s):  
Molecular Weight ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Low Molecular Weight ◽  
Colon Cancer Cells ◽  
Grape Seeds ◽  
Human Colon Cancer ◽  
The Impact ◽  
Human Colon Cancer Cells

Randomized Phase II Trial of Docetaxel Plus Thalidomide in Androgen-Independent Prostate Cancer

2004 ◽  
Vol 22 (13) ◽  
pp. 2532-2539 ◽  
Author(s):  
William L. Dahut ◽  
James L. Gulley ◽  
Philip M. Arlen ◽  
Yinong Liu ◽  
Katherine M. Fedenko ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Weight ◽  
Phase Ii ◽  
Low Molecular Weight Heparin ◽  
Phase Ii Trial ◽  
Low Molecular Weight ◽  
Randomized Phase Ii ◽  
The Impact ◽  
Docetaxel Group ◽  
Androgen Independent

Purpose Both docetaxel and thalidomide have demonstrated activity in androgen-independent prostate cancer (AIPC). We compared the efficacy of docetaxel to docetaxel plus thalidomide in patients with AIPC. Methods Seventy-five patients with chemotherapy-naïve metastatic AIPC were randomly assigned to receive either docetaxel 30 mg/m2 intravenously every week for 3 consecutive weeks, followed by a 1-week rest period (n = 25); or docetaxel at the same dose and schedule, plus thalidomide 200 mg orally each day (n = 50). Prostate-specific antigen (PSA) consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decline, and time to progression. Results After a median potential follow-up time of 26.4 months, the proportion of patients with a greater than 50% decline in PSA was higher in the docetaxel/thalidomide group (53% in the combined group, 37% in docetaxel-alone arm). The median progression-free survival in the docetaxel group was 3.7 months and 5.9 months in the combined group (P = .32). At 18 months, overall survival in the docetaxel group was 42.9% and 68.2% in the combined group. Toxicities in both groups were manageable after administration of prophylactic low-molecular-weight heparin in the combination group. Conclusion In this randomized phase II trial, the addition of thalidomide to docetaxel resulted in an encouraging PSA decline rate and overall median survival rate in patients with metastatic AIPC. After the prophylactic low-molecular-weight heparin was instituted to prevent venous thromboses, the combination regimen was well tolerated. Larger randomized trials are warranted to assess the impact of this combination.

Low molecular weight dextran sulfate as complement inhibitor and cytoprotectant in solid organ and islet transplantation

2008 ◽  
Vol 45 (16) ◽  
pp. 4084-4094 ◽  
Author(s):  
Rolf Spirig ◽  
Thusitha Gajanayake ◽  
Olle Korsgren ◽  
Bo Nilsson ◽  
Robert Rieben
Keyword(s):  
Molecular Weight ◽  
Islet Transplantation ◽  
Dextran Sulfate ◽  
Low Molecular Weight ◽  
Solid Organ ◽  
Complement Inhibitor

scholarly journals Control of IBMIR Induced by Fresh and Cryopreserved Hepatocytes by Low Molecular Weight Dextran Sulfate versus Heparin

2017 ◽  
Vol 26 (1) ◽  
pp. 71-81 ◽  
Author(s):  
Elisabet Gustafson ◽  
Sana Asif ◽  
Huda Kozarcanin ◽  
Graciela Elgue ◽  
Staffan Meurling ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Dextran Sulfate ◽  
Cell Loss ◽  
Hepatocyte Transplantation ◽  
Low Molecular Weight ◽  
Cascade Systems ◽  
Cell Counts ◽  
Compatible Blood

Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 μg/ml) to attenuate the degree of activation of the cascade systems were monitored. The effect was also compared to conventional anticoagulant therapy using unfractionated heparin (1 IU/ml). Both fresh and freeze–thawed hepatocytes elicited IBMIR to the same extent. LMW-DS reduced the platelet loss and maintained the cell counts at the same degree as unfractionated heparin, but controlled the coagulation and complement systems significantly more efficiently than heparin. LMW-DS also attenuated the IBMIR elicited by freeze–thawed cells. Therefore, LMW-DS inhibits the cascade systems and maintains the cell counts in blood triggered by both fresh and cryopreserved hepatocytes in direct contact with ABO-matched blood. LMW-DS at a previously used and clinically applicable concentration (100 μg/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.

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