Characterization of currently marketed heparin products: Adverse event relevant bioassays

Sommers, Cynthia D.; Montpas, Nicolas; Adam, Albert; Keire, David A.

doi:10.1016/j.jpba.2012.04.017

Cited by 8 publications

(4 citation statements)

References 30 publications

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“…[11][12][13][14] In this study, to further develop and rene this approach, the 2D-1 H- 13 C-HSQC experiment was applied to a larger set of samples obtained from multiple sources that had been thoroughly characterized by a number of orthogonal techniques. 4,7,15,16 The HSQC experiment detects the effect of the carbon nucleus connected to a proton indirectly via the proton magnetization. The instrument response is dependent on experimental parameters and the magnitude of the one-bond scalar-coupling between 1 H- 13 C pairs ( 1 J CH ), the proton T 1 and T 2 relaxation times, J HH evolution during the polarization transfer period and offset effects on the 13 C-nucleus pulses.…”

Section: Introductionmentioning

confidence: 99%

Characterization of currently marketed heparin products: composition analysis by 2D-NMR

2013

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Section: Introductionmentioning

confidence: 99%

Characterization of currently marketed heparin products: composition analysis by 2D-NMR

2013

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“…Furthermore, there were some subtle differences in response between CS3.0, CS3.1 and CS3.2 which could indicate that there may be some specific features that influence the activation of kallikrein. Previously it has been shown that OSCS can activate bradykinin [ 4 , 31 ] and this study under the conditions used the is no bradykinin activity without kallikrein formation. Concentrations of OSCS that generated the same level of kallikrein, also generated the same amount of bradykinin, consistent with prekallikrein activation being the sole mechanism through which OSCS influences bradykinin generation.…”

Section: Discussionmentioning

confidence: 77%

The effect of increasing the sulfation level of chondroitin sulfate on anticoagulant specific activity and activation of the kinin system

et al. 2018

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Oversulfated chondroitin sulfate (OSCS) was identified as a contaminant in certain heparin preparations as the cause of adverse reactions in patients. OSCS was found to possess both plasma anticoagulant activity and the ability to activate prekallikrein to kallikrein. Differentially sulfated chondroitin sulfates were prepared by synthetic modification of chondroitin sulfate and were compared to the activity of OSCS purified from contaminated heparin. Whilst chondroitin sulfate was found to have minimal anticoagulant activity, increasing sulfation levels produced an anticoagulant response which we directly show for the first time is mediated through heparin cofactor II. However, the tetra-sulfated preparations did not possess any higher anticoagulant activity than several tri-sulfated variants, and also had lower heparin cofactor II mediated activity. Activation of prekallikrein was concentration dependent for all samples, and broadly increased with the degree of sulfation, though the di-sulfated preparation was able to form more kallikrein than some of the tri-sulfated preparations. The ability of the samples to activate the kinin system, as measured by bradykinin, was observed to be through kallikrein generation. These results show that whilst an increase in sulfation of chondroitin sulfate did cause an increase in anticoagulant activity and activation of the kinin system, there may be subtler structural interactions other than sulfation at play given the different responses observed.

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“…On the other hand, DS will probably not be as antigenic as CS in the case of HNK-1 because, as opposed to the latter, which can contain the antigen 3-sulfated GlcA epitope, DS does not present this motif (Table 2). Nonetheless, while not confirming the hypotensive side-effect, there are studies that indicate that oversulfated DS can cause kallikrein activation [236,237].…”

Section: Drawbacksmentioning

confidence: 99%

Galactosaminoglycans: Medical Applications and Drawbacks

et al. 2019

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Galactosaminoglycans (GalAGs) are sulfated glycans composed of alternating N-acetylgalactosamine and uronic acid units. Uronic acid epimerization, sulfation patterns and fucosylation are modifications observed on these molecules. GalAGs have been extensively studied and exploited because of their multiple biomedical functions. Chondroitin sulfates (CSs), the main representative family of GalAGs, have been used in alternative therapy of joint pain/inflammation and osteoarthritis. The relatively novel fucosylated chondroitin sulfate (FCS), commonly found in sea cucumbers, has been screened in multiple systems in addition to its widely studied anticoagulant action. Biomedical properties of GalAGs are directly dependent on the sugar composition, presence or lack of fucose branches, as well as sulfation patterns. Although research interest in GalAGs has increased considerably over the three last decades, perhaps motivated by the parallel progress of glycomics, serious questions concerning the effectiveness and potential side effects of GalAGs have recently been raised. Doubts have centered particularly on the beneficial functions of CS-based therapeutic supplements and the potential harmful effects of FCS as similarly observed for oversulfated chondroitin sulfate, as a contaminant of heparin. Unexpected components were also detected in CS-based pharmaceutical preparations. This review therefore aims to offer a discussion on (1) the current and potential therapeutic applications of GalAGs, including those of unique features extracted from marine sources, and (2) the potential drawbacks of this class of molecules when applied to medicine.

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Characterization of currently marketed heparin products: Adverse event relevant bioassays

Cited by 8 publications

References 30 publications

Characterization of currently marketed heparin products: composition analysis by 2D-NMR

Characterization of currently marketed heparin products: composition analysis by 2D-NMR

The effect of increasing the sulfation level of chondroitin sulfate on anticoagulant specific activity and activation of the kinin system

Galactosaminoglycans: Medical Applications and Drawbacks

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