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Biomedical subjects

J N Shanberge

Publications and source records attributed to J N Shanberge.

At least 19 recordsLinked to original sources
PubMed1995

Effect of aspirin and iloprost on adhesion of platelets to intact endothelium in vivo.

Aspirin has been used for the prevention of platelet thrombi, both prophylactically and therapeutically, in a wide variety of conditions. Although the dosage used has also varied, it is now suggested that lower doses are as efficacious and probably safer than higher doses. Part of the problem in determining the amount to be used is that aspirin not only inhibits the formation of the proaggregatory thromboxane A2 in the platelet, at any dose, but also that it interferes with the production of prostacyclin (antiaggregatory) by the endothelial cells in a dose-dependent manner. Previously, utilizing a hamster cheek pouch preparation, we demonstrated that platelets would adhere to intact endothelium, in vivo, after an otherwise ineffectual dose of thrombin if the glycosaminoglycans of endothelial cells that produce antithrombin activity were first neutralized by protamine. Reported here is the effect of aspirin on the platelet thrombi produced by thrombin in this manner. Aspirin was found to inhibit platelet thrombosis by thrombin in low doses (optimum dose 2.5 mg/kg body weight), but at higher doses the aspirin was less effective. Actually, the higher doses of aspirin promoted platelet thrombus formation by thrombin even in the absence of protamine. Infusion of iloprost, an analog of prostacyclin, also prevented platelet thrombus formation by protamine and thrombin with or without the administration of aspirin, and this infusion overcame the thrombogenicity of the higher doses of aspirin. The results of these experiments in the hamster suggest that the optimum dosage of aspirin in the clinical treatment of prophylaxis of thrombosis in human patients would be 160 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

A method for the quantitation of protamine in plasma.

A unique and simple colorimetric method for the quantitation of plasma protamine levels has been developed. The method is established on the competitive binding displacement mechanism between protamine and heparin-azure A dye complex, and the metachromatic color change of azure A dye in the presence of heparin. Because the method is based on the clinical specificity of protamine as the heparin antagonist, it is specific for protamine quantitation. Plasma protamine levels determined by this method are within 94% of accuracy when compared with their aqueous counterparts determined by the conventional Lowry protein assay. Since the method measures the protamine excess after heparin neutralization, it potentially could be employed during clinical heparin reversal with protamine to monitor protamine excess. In addition, the method may provide a useful means to identify the mechanism of the so-called "heparin rebound".

Azure Stains↗
PubMed1994

Hemangioma of the uterus associated with hereditary hemorrhagic telangiectasia.

BACKGROUND: Hemangiomas of the uterus are rare. Involvement of the uterus with hereditary hemorrhagic telangiectasia causing menorrhagia is also rare. To our knowledge, only one case of combined uterine hemangioma and hereditary hemorrhagic telangiectasia has ever been reported. CASE: A 34-year-old woman was to undergo hysterectomy for menorrhagia unresponsive to treatment. Before surgery, she was found to have typical telangiectases associated with hereditary hemorrhagic telangiectasia. The fundus of the uterus contained a hemangioma extending from the serosa to the endometrium. CONCLUSION: Vascular malformation have been found in various organs in individuals with hereditary hemorrhagic telangiectasia. Although involvement of the uterus in hereditary hemorrhagic telangiectasia is uncommon, telangiectasia should be considered in any patient with menorrhagia resistant to treatment.

Adult↗
PubMed1992

Analysis of fresh frozen plasma administration with suggestions for ways to reduce usage.

A programme for the daily monitoring of Fresh Frozen Plasma (FFP) usage, combined with continuous education in the correct use of FFP, was started at William Beaumont Hospital in 1985. In 2 years, this had resulted in a 77% reduction in FFP usage. An analysis of the type of cases which received FFP, after the major reduction had occurred, from July, 1985 through June, 1989 is presented. During this time 2,612 units were administered to 873 patients, an average of 54 units per month. According to the accepted criteria established by the Hospital Transfusion Committee, 67% of the transfused units on the medical service were deemed indicated, compared with 54% on the surgical service. Most of the FFP was used to treat patients with liver disease, or receiving coumadin, or undergoing coronary bypass surgery. Conditions which will decrease the need for FFP administration are also presented for consideration. The results indicate that a consistent monitoring and education programme can keep blood and blood component usage at a defensible minimum.

Blood Component Transfusion↗
PubMed1990

Production of thrombi on intact endothelium by use of antiheparin agents in vivo.

It had been suggested that antithrombin activity on the surface of intact endothelial cells may play a role in inhibiting platelet adhesion and thrombus formation. The antithrombin activity may be due to thrombomodulin or to activation of antithrombin III by glycosaminoglycans or thrombomodulin, or possibly a combination of these. This inhibitory activity has been shown to be affected by such antiheparin agents as protamine, hexadimethrine bromide (Polybrene; Aldrich Chemical Co., Milwaukee, Wis.) and platelet factor 4, as well as by such enzymes as heparinase and heparitinase. We have used a hamster cheek pouch preparation to observe thrombus formation in vivo in a normal vascular flow, to determine whether the production of thrombi by thrombin can be enhanced by antiheparin agents. After intra-arterial injection or topical application of protamine or hexadimethrine bromide, platelet adhesion and thrombus formation on intact arteriolar endothelium was produced by a dose of thrombin, which when injected alone had no effect. No thrombi were found in venules or capillaries. Injection of heparin before or after the antiheparin agents necessitated a larger dose to enhance the action of thrombin. On electron microscopy the thrombi were found to consist primarily of platelets adherent to an intact endothelium. The possible clinical implications of these observations are discussed.

Animals↗
PubMed1989

Influence of platelet factor 4 on the neutralization of heparin by protamine.

In vitro, PF4 is comparable to protamine sulfate in the neutralization of heparin, but the complexes formed with heparin are different. Even with an excess of PF4, no large PF4-heparin complexes are formed and none of the complexes are able to activate ATIII, nor do these complexes dissociate on incubation in plasma at 37 degrees C. The action of PF4 and protamine is complementary. However, excess protamine displaces PF4 or prevents its complexing with heparin. When excess protamine is used to neutralize heparin in the presence of PF4, large heparin-protamine complexes are formed incorporating PF4. In contrast to the heparin-protamine complexes formed without PF4, these do not activate ATIII nor do they dissociate on incubation. Since PF4 is liberated during ECB procedures, its contribution to the stability of heparin-protamine complexes in vivo may influence the amount of protamine needed to neutralize heparin as well as affect the reactions which have been reported on injection of protamine after ECB.

Animals↗
PubMed1987

Interrelationship of protamine and platelet factor 4 in the neutralization of heparin.

To determine the interaction of platelet factor 4 (PF4) and protamine sulfate in the neutralization of heparin in plasma in vitro studies were carried out using a tritium-labeled heparin and a PF4 tagged with 14C. Plasmas treated with various combinations of PF4, protamine and heparin were chromatographed on Sephadex G200 and the fractions were tested for both radioactivity and antithrombin activity. PF4 was comparable to protamine in its ability to neutralize heparin, but the complexes formed with heparin were different. In contrast to protamine, when heparinized plasma was treated with an excess of PF4, no large PF4-heparin complexes were formed and none of the PF4-heparin complexes which did form were able to activate antithrombin III (ATIII). Also, incubation of PF4-neutralized, heparinized plasma at 37 degrees C did not result in liberation of heparin and prolongation of the thrombin clotting time as was found with protamine-neutralized plasma. The action of protamine and PF4 is complimentary. When half the neutralizing dose of each was added together to heparinized plasma, no immediate antithrombin activity remained. When a neutralizing dose of protamine was added to PF4-neutralized, heparinized plasma, the protamine displaced the PF4 from its complexes with heparin. The large protamine-heparin complexes which formed also contained PF4 but could not activate fresh ATIII as has been demonstrated with protamine-heparin complexes without PF4. On incubation of the protamine-PF4-neutralized, heparinized plasmas for 5 hours at 37 degrees C, the large complexes were broken down but no active heparin appeared. The results of these experiments may have some bearing on the amount of protamine needed for the neutralization of heparin following extracorporeal bypass procedures, when large amounts of PF4 may have been released from activated or disrupted platelets.

Chromatography↗
PubMed1987

Heparin-protamine complexes in the production of heparin rebound and other complications of extracorporeal bypass procedures.

Neutralization by protamine of the heparin activation of antithrombin III in plasma, in vitro, represents an equilibrium reaction in which by mass action heparin remains complexed only in the presence of an excess of protamine. Loss of this excess through enzymatic breakdown of the free protamine leads to instability of the complexes with liberation of the heparin, reestablishing antithrombin activity. This "heparin rebound" can also be produced by an increase in heparin levels or increased amounts of antithrombin III. These phenomena could occur after extracorporeal bypass procedures by an increase in heparin from whatever source or by added antithrombin III, through transfusions of fresh frozen plasma. A larger excess of protamine does not itself act as an anticoagulant but produces large heparin-protamine complexes that can still activate antithrombin III. Such large complexes, formed in vivo, could possibly block the pulmonary microcirculation and cause the acute pulmonary hypertension that has been reported after protamine infusions.

Extracorporeal Circulation↗
PubMed1983

Effect of protamine sulfate on antithrombin III activity.

When protamine sulfate was added to heparinized plasma in vitro for neutralization of heparin, the activities on both thrombin and Xa known as heparin cofactor in antithrombin action were completely abolished. However, progressive activities on thrombin and Xa both recovered within 30 minutes after protamine sulfate addition. When equivalent heparin was again added, heparin cofactor activity was immediately restored. Based on the fact that protamine sulfate did not show any direct action on the antithrombin III molecule, the presence of AT III with progressive activity was considered to play an important role in the rebound phenomenon of heparin after heparin neutralization with protamine sulfate.

Antithrombin III↗
PubMed1981

The interaction of protein-bound heparin and antithrombin III.

When commercially prepared porcine mucosal heparin is added to human plasma, some of the heparin fractions form a complex with antithrombin III activating it to an immediate inhibitor of thrombin as well as of other serine proteases. Certain fractions of heparin may complex with other proteins such as alpha 2-macroglobulin, another progressive inhibitor of thrombin. Without complexing with antithrombin III, this protein-bound heparin fraction(s) still retains the capacity to activate it to an immediate inhibitor of thrombin. Protamine sulfate inactivates those heparin fractions that bind to antithrombin III but not those bound to alpha 2-macroglobulin. Activated antithrombin III may undergo a molecular change in the presence of protamine which not only changes it back to a progressive inhibitor but makes it resistant to activation by the protein-bound heparin fraction(s). However, it can still be reactivated by other heparin fractions in fresh whole heparin. The observations presented may help explain heparin "rebound" in patients believed adequately neutralized with protamine.

Animals↗