PMID- 17164496
OWN - NLM
STAT- MEDLINE
DCOM- 20070619
LR  - 20121115
IS  - 1076-0296 (Print)
IS  - 1076-0296 (Linking)
VI  - 13
IP  - 1
DP  - 2007 Jan
TI  - Relative neutralization of the biological actions of sulfaminoheparosans (K5 
      derivatives) and heparins by protamine sulfate.
PG  - 52-64
AB  - Biosynthetic, semisynthetic, and synthetic analogues of heparins are currently 
      developed as substitute antithrombotic agents for heparin. Sulfaminoheparosan 
      (SAH) represents a bacterial polysaccharide (K5)-derived antithrombotic polymer 
      from which pharmacologically active products with varying molecular weights (5-25 
      kDa) can be derived. These agents have been shown to exhibit pharmacologic 
      effects comparable to heparins. The objective of this investigation is to 
      determine the relative neutralization profile of various SAH derivatives, also 
      called as bioheparins, by protamine sulfate. Four SAH fractions with varying 
      molecular weights (20, 9, 7, and 6 kDa), a low molecular weight heparin (LMWH), 
      tinzaparin, and unfractionated heparin (UFH) were supplemented to normal human 
      pool plasma over a concentration range of 6.2 to 100 microg/mL. A fixed amount of 
      protamine sulfate at 25 microg/mL (final concentration) was supplemented to 
      determine the neutralization profile by performing tests such as prothrombin time 
      (PT), activated partial thromboplastin time (APTT), Heptest, prothrombin-induced 
      clotting time (PiCT), and amidolytic anti-Xa and anti-IIa assays. Protamine 
      sulfate produced varying degrees of neutralization of all bioheparin fractions in 
      the clotting assays. In the amidolytic anti-IIa assay relatively stronger 
      inhibition was noted for all agents than inhibition of FXa. On a cumulative basis 
      the neutralization profile of SAHs was comparable with heparins. These results 
      suggest that the anticoagulant activities of SAH derivatives can be antagonized 
      by protamine sulfate. These studies warrant further in vivo investigation to 
      validate the relative neutralization profile of sulfaminoheparosans.
FAU - Maddineni, Jyothi
AU  - Maddineni J
AD  - Department of Pharmacology, Loyola University Medical Center, Maywood, Illinois 
      60153, USA.
FAU - Hoppensteadt, Debra A
AU  - Hoppensteadt DA
FAU - Cornelli, Umberto
AU  - Cornelli U
FAU - Manoni, Marco
AU  - Manoni M
FAU - Fareed, Jawed
AU  - Fareed J
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Clin Appl Thromb Hemost
JT  - Clinical and applied thrombosis/hemostasis : official journal of the 
      International Academy of Clinical and Applied Thrombosis/Hemostasis
JID - 9508125
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Heparin Antagonists)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Polysaccharides, Bacterial)
RN  - 0 (Protamines)
RN  - 42615-44-1 (capsular polysaccharide K5)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Bacterial Capsules
MH  - Blood Coagulation/*drug effects
MH  - Blood Coagulation Tests
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Fibrinolytic Agents
MH  - Heparin/*analogs & derivatives/pharmacology
MH  - Heparin Antagonists/*pharmacology
MH  - Heparin, Low-Molecular-Weight/pharmacology
MH  - Humans
MH  - Molecular Weight
MH  - Polysaccharides, Bacterial/*drug effects/pharmacology
MH  - Protamines/*pharmacology
MH  - Titrimetry
EDAT- 2006/12/14 09:00
MHDA- 2007/06/20 09:00
CRDT- 2006/12/14 09:00
PHST- 2006/12/14 09:00 [pubmed]
PHST- 2007/06/20 09:00 [medline]
PHST- 2006/12/14 09:00 [entrez]
AID - 13/1/52 [pii]
AID - 10.1177/1076029606296403 [doi]
PST - ppublish
SO  - Clin Appl Thromb Hemost. 2007 Jan;13(1):52-64. doi: 10.1177/1076029606296403.