Biomedical subjects

C L Teng

Publications and source records attributed to C L Teng.

8 recordsLinked to original sources

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".

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PubMed1991

The use of immobilized protamine in removing heparin and preventing protamine-induced complications during extracorporeal blood circulation.

Heparin, currently used in extracorporeal blood circulation procedures, may lead to hemorrhagic complications. Protamine, used for reversal of heparin-induced anticoagulation at the end of such procedures, can cause adverse hemodynamic responses. To prevent both types of complications, we have developed a reactor device containing immobilized protamine (i.e., a protamine bio-reactor) that can be placed at the distal end of the circuit, thus providing simultaneous extracorporeal heparin removal and protamine treatment. In preliminary in vivo studies involving dogs at a blood flow of 100 ml/min, the bio-reactor removed about 50% of the administered dose of heparin (i.e., 100 units/kg) in 10 min. While rapid injection of protamine in dogs anticoagulated with heparin produced a transient and significant (P less than 0.005) decreases in systemic arterial blood pressure (-39.5 +/- 9.2 mmHg), cardiac output (-1.59 +/- 0.23 L/min), and mixed venous oxygen saturation (-7.5 +/- 1.3%) and increases in pulmonary artery systolic (+12.7 +/- 4.4 mmHg) and diastolic pressures (+10.0 +/- 3.6 mmHg), the use of the protamine bio-reactor did not elicit any statistically significant change in any of the variables measured. Hemolysis was not significant, as reflected by a statistically insignificant change of the animals' red blood cell counts, hematocrits, and total hemoglobin values. In addition, hemolytic complement was found to be reduced only by 10% in animals with the protamine bio-reactor, whereas it was reduced rapidly by 20% in animals receiving intravenous protamine administration and progressively by 20% in control animals with a sham reactor that contained no protamine. Furthermore, the use of the protamine bio-reactor also significantly reduced the protamine-induced transient thrombocytopenic and granulocytopenic responses. The white blood cell counts and platelet counts decreased to 87.7 +/- 7.5 and 83.3 +/- 5.0% of baseline, respectively, in dogs with the protamine bio-reactor compared to 35.5 +/- 14.3 and 32.1 +/- 8.1% of baseline in dogs receiving intravenous protamine. The protamine bio-reactor may provide a unique means to simultaneously control both heparin- and protamine-induced complications.

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PubMed1989

A facile colorimetric protamine titration method.

On the basis of the reversible, competitive binding of protamine and azure A dye to heparin, a facile, colorimetric protamine titration method was developed. The method uses azure A dye as the titration indicator and has thus replaced the time-consuming clotting assay in the traditional protamine titration method with a rapid colorimetric assay. It offers the same accuracy in estimating the titration end point as the traditional titration method but allows the processing time to be significantly shortened. With the use of a premade diagnostic kit containing a fixed amount of azure A dye and various amounts of protamine, the titration end point can be determined in less than 5 minutes. This new colorimetric protamine titration method should provide clinicians with an easy and reliable means to accurately estimate the protamine dose required for heparin neutralization. It should also assist medical laboratories in preparing plasma samples that are free of heparin interference for routine coagulation tests. In a reverse manner, the colorimetric assay can also be used with a heparin titration procedure to quickly assess the heparin dose required for protamine reversal. For patients who have received overdoses of protamine, the availability of a facile heparin titration method may offer the prospect of exercising a heparin "back titration."

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PubMed1988

The effect of compactional pressure on urease activity.

Jack bean urease is a proteinaceous enzyme, MW approximately 489 kD, readily soluble in water but losing activity when sheared in solution at stresses as low as 2.5 Pa. There is a need for controlled-release forms of many of the new genetically engineered peptide and polypeptide drugs with high specific activities. The simplest form of controlled release would be a sterile compressed pellet of the active component inserted subdermally. However, "activity" may be lost on compaction. Urease can be regarded as a model protein which may lose activity when sheared during compaction in the dry state. Tablets of urease weighing 100 mg were compressed over a range of pressures from 60 to 1750 MPa. No relative loss of activity would be detected following compaction at pressures up to 474 MPa. Above this limiting pressure there was a 50% loss of relative activity, evidently by a compactional effect on the protein quaternary and tertiary structures. No direct relationship was observed between stress (compactional pressure) and inactivation.

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PubMedDate not supplied

A novel approach to anticoagulation control.

Heparin used in extracorporeal therapy often leads to bleeding complications. Protamine used for heparin reversal can cause adverse hemodynamic responses. To control both types of complications, a cellulosic hollow-fiber filter device containing immobilized protamine (defined as a protamine filter) was developed. In vivo experiments with dogs showed that the filter not only removed more than 80% of the anticoagulant activity of heparin, but also caused no clinically significant hemodynamic response. In addition, the protamine filter also significantly attenuated both the thrombocytopenic and granulocytopenic responses associated with the use of protamine. Moreover, the use of immobilized protamine considerably reduced activation of the blood complement system by free protamine.

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PubMedDate not supplied

Rapid and precise whole blood protamine titration.

A rapid and precise whole blood protamine titration method was developed. The method uses azure A dye as the titration indicator and thereby replaces the tedious and time-consuming clotting assay with a facile colorimetric assay. The method provides the same accuracy in estimating the titration end-point, but allows the processing time to be shortened to that required by current clinical methods. The simplicity, flexibility, speed, and accuracy offered by the method, and the ability to use whole blood specimens for the measurements, should allow the method to be used by clinicians in the operating room or during a surgical procedure to estimate the adequate protamine dose required for heparin reversal.

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PubMedDate not supplied

A filter device for the prevention of both heparin- and protamine-induced complications associated with extracorporeal therapy.

When extracorporeal blood circulation (ECBC) is used, systemic heparinization is necessary to prevent clotting of the blood in the extracorporeal circuit. However, the high circulating heparin concentration needed often leads to bleeding complications. To avoid these, protamine, a heparin antagonist, is administered at the conclusion of the ECBC procedure to reverse the anticoagulant activity of heparin. Intravenous administration of protamine can cause hypotension and shock. To date, there has been no real alternative to control the bleeding risks associated with systemic use of heparin and the adverse effects resulting from heparin reversal with protamine. A novel approach that might control both the heparin- and the protamine-induced complications is suggested. It consists of placing a blood-compatible filter device containing immobilized protamine (a protamine filter) at the distal end of the ECBC apparatus. The filter removes heparin after heparin serves its anticoagulant purpose in the extracorporeal circuit and before blood is returned to the patient. The filter also allows for an external protamine treatment. Since protamine toxicity results from the direct contact of protamine with cells of the liver, lungs, and other organ tissues, the use of an external protamine treatment would minimize it. Protamine was covalently immobilized onto a cellulosic hollow fiber bundle obtained from a clinically used hemodialyzer. The bundle was accessed to the vascular system of a dog by femoral artery and vein cannulation. In in-vivo experiments the protamine-bound fiber bundle not only removed heparin from the extracorporeal circuit, but also caused no clinically significant hemodynamic change in the animal.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMedDate not supplied

A protamine filter for extracorporeal blood heparin removal.

Heparin employed in extracorporeal circuits often leads to hemorrhagic complications. Protamine employed for heparin neutralization can cause adverse hemodynamic responses. To control both types of complications, the authors propose an approach that consists of placing a filter device containing immobilized protamine (defined as a protamine filter) at the termination of the extracorporeal blood circulation (ECBC) procedure. This protamine filter would remove heparin from the extracorporeal circuit before heparin is returned to the patient. Meanwhile, the filter would also permit external protamine treatment. Since protamine toxicity generally results from the interaction of protamine with certain cells present in the liver, lungs, and tissues, the use of external protamine would minimize its potential adverse effects. Protamine was immobilized on a hollow fiber bundle obtained from a conventional hemodialyzer. Preliminary studies show that the protamine bound bundle is capable of neutralizing the anticoagulant activity of heparin both in vitro and in vivo. In addition, the protamine filter has abolished the hypotensive response normally associated with protamine reversal of heparin, as indicated by the insignificant changes in blood pressure, pulse rate, pulmonary artery systolic/diastolic pressures, and cardiac output. Further in vivo studies involving the use of dogs, as well as investigation of the activation of the complement system by the protamine filter, are currently being conducted.

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