Comparative studies on the topical administration of mucopolysaccharide and heparin ointments in nonhuman primates.
Mucopolysaccharide polysulfate (MPS) represents a mammalian-derived sulfated polysaccharide. Because the origin and structure of heparins is similar to MPS, this study was conducted to compare 2 ointment formulations containing MPS or heparin with a placebo ointment on tissue factor pathway inhibitor (TFPI) released in nonhuman primates (Macaca mulatta). A primate colony composed of 18 animals, housed at Loyola University Medical Center, was used in compliance with an Institutional Animal Care and Use Committee (IACUC)-approved protocol. Mucopolysaccharide polysulfate (4.5%), heparin (4.5%), and a placebo ointment were topically applied to individual groups of primates in a crossover study for periods of up to 2 weeks. Blood samples were drawn on days 1, 2, 5, 7, and 10. The anticoagulant effects (activated partial thromboplastin time [APTT], Heptest, thrombin time [TT]), TFPI antigen and functional levels, thrombin activatable fibrinolytic inhibitor (TAFI), and antiheparin platelet factor 4 antibodies (AHPF4 abs) were measured in citrated plasma. All data were compiled as mean +/- 1 standard deviation and compared in groups. Topical administration of both the MPS and heparin ointments resulted in no measurable anticoagulant effects in the primate model; however, MPS produced a concentration-dependent release of TFPI antigen and a functional activity that was stronger than the effects observed with heparin. A decrease in TAFI activation was also observed in the MPS-treated primates. In addition, in the heparin-treated group, a slight increase in AHPF4 abs was observed. In conclusion, MPS showed a stronger release of TFPI than heparin that was not associated with a strong anticoagulant effect. Moreover, MPS downregulated TAFI, resulting in an enhanced fibrinolytic effect.
Hoppensteadt
Debra A
DA
Department of Pathology, Loyola University Chicago, Chicago, Illinois, USA. dhoppen@lumc.edu
Neville
Brian
B
Schultz
Christopher
C
Jeske
Walter
W
Raake
Wolfram
W
Fareed
Jawed
J
D000287:Administration, Topical; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005343:Fibrinolytic Agents / Q000276:immunology / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000276:immunology / Q000494:pharmacology*; D008074:Lipoproteins / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D009823:Ointment Bases / Q000494:pharmacology*; D010314:Partial Thromboplastin Time; D010978:Platelet Factor 4 / Q000276:immunology; D013918:Thrombin Time
D001323:Autoantibodies; D005343:Fibrinolytic Agents; D006025:Glycosaminoglycans; D008074:Lipoproteins; D009823:Ointment Bases; C051928:lipoprotein-associated coagulation inhibitor; C052717:mucopolysaccharide polysulfate; D010978:Platelet Factor 4; D006493:Heparin