Quantification of Circulating Proteins: Theory and Applications Based on Analysis of Plasma Protein Levels

ISBN-13: 9789400976627 / Angielski / Miękka / 2011 / 264 str.

Wim Th Hermens; George M. Willems; Marja P. Visser

Opis

Less than 50 years ago it was discovered that steady-state protein concentrations in plasma are the net result of continuous elimination and synthesis of protein molecules. The first quanti- tative studies on the turnover and distribution of plasma pro- teins were made around 1950, after the introduction of radio- labeled protein preparations. Around 1970, another development in quantitative interpre- tation of circulating proteins was initiated in clinical enzy- mology. Estimation of cumulative release into plasma of cellular enzymes can be helpful in a variety of diseases to assess the extent of tissue damage and to evaluate therapy. Enzymes can be considered as biological tracers, i.e. minute quantities of protein can be accurately determined by their spe- cific catalytic activities. However, radioactive tracers permit direct estimates of turnover and distr ibution by measurement of excreted radioactivity, possibilities that are not available for enzymes. Consequently, only a few techniques used in tracer studies with radiolabeled proteins can be applied to circulating tissue enzymes and this may explain the lack of communication between the fields of plasma protein metabolism and quantitative clinical enzymology. In the present study a summary is given of the basic methods used in both fields, with emphasis on the equivalence of various models and formalisms used by different authors. It is shown that major limitations in the study of circulating tissue enzymes can be overcome if two different, but simultaneously released, en- zymes can be measured. The resulting method will also be applied to plasma protein metabolism.

Spis treści

1: Introduction.- 1.1 Quantitative description of circulating proteins.- 1.2 Presentation of theory and applications.- A: Physiological basis, choice of models and quantitative methods.- 2: Turnover and distribution of circulating tissue enzymes.- 2.1 Introduction.- 2.2 Variability of tissue enzyme content.- 2.3 Relation between leakage of cellular enzymes and cell death.- 2.4 Enzyme release from different cellular compartments.- 2.5 Pathways for the transport of cellular proteins from tissues to plasma.- 2.6 Factors preventing tissue enzymes from reaching circulation.- 2.7 Elimination of tissue enzymes from circulation.- 3: Turnover and distribution of plasma proteins.- 3. 1 Introduction.- 3.2 Delivery of plasma proteins to circulation.- 3.3 Exchange of protein between plasma and extravascular compartments.- 3.4 Elimination of plasma proteins from circulation.- 3. 5 Variability of circulatory parameters in man.- 4: Methods and models used in quantitative studies of circulating proteins.- 4.1 Introduction.- 4.2 Basic compartmental models.- 4.3 Equivalence of different methods and formalisms.- 4.4 Quantification of in vivo release of protein.- 5: Sources of error in quantification of circulating proteins.- 5.1 Introduction.- 5.2 Hazards in estimating circulatory parameters from tracer kinetics.- 5.3 Errors caused by purification and labeling.- 5.4 Accuracy in calculation of cumulative protein release.- 5.5 Behaviour of circulating proteins in the dog.- B : Applications.- 6: Assessment of myocardial damage from plasma levels of cardiac enzymes.- 6 1 Introduction.- 6.2 A model for circulating cardiac enzymes.- 6.3 Estimation of catabolic rate constants.- 6.4 Accuracy in calculation of cumulative release of cardiac enzymes.- 6.5 The extent of myocardial damage after acute myocardial infarction.- 6.6 The extent of myocardial damage after open-heart surgery.- 7: Changes in circulating mass of plasma proteins during the acute phase response.- 7.1 Introduction.- 7.2 Plasma volume changes after acute myocardial infarction.- 7.3 Plasma volume expansion and the negative acute phase response.- 7.4 Consumption of proteinase inhibitors in the acute phase after myocardial infarction.- 7.5 Calculation of catabolic rate constants from the acute phase response.- 8: Dose-calculation of blood coagulation factors for infusion therapy.- 8.1 Introduction ..- 8.2 A model for circulating coagulation factors.- 8.3 Estimation of circulatory parameters for different coagulation factors.- 8.4 Effects of a single dose, intermittent doses and continuous infusion.- 8. 5 Complications in dose calculation.- 9: A review of data on the turnover and distribution of circulating proteins.- 9.1 Experimental procedures.- 9. 2 Techniques for the analysis of data.- 9.3 List of plasma proteins.- 9.4 Circulatory parameters for plasma proteins in man.- 9.5 Circulatory parameters for plasma proteins in the dog, rabbit and rat.- 9. 6 List of circulating tissue enzymes.- 9.7 Circulatory parameters for tissue enzymes in man.- 9.8 Circulatory parameters for tissue enzymes in the dog,rabbit and rat.- Appendix: Derivation of mathematical expressions.- References.