Standard coagulation tests have a low specificity and sensitivity for diagnosing disseminated intravascular coagulation. The aim of this study was to determine whether whole blood thromboelastometry (TEM) detects lipopolysaccharide (LPS)-induced changes in coagulation. Blood samples from 10 pigs were drawn at baseline, before and at the end of LPS infusion and 2, 3, 4 and 5 h after the start of endotoxinemia. Simultaneous to TEM, standard coagulation tests and extended coagulation analysis including tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) were performed. Endotoxinemia resulted in a significant acceleration of the nonactivated TEM (NATEM) clotting time 2 h after the end of LPS infusion; in contrast, the changes in international normalized ratio and activated partial thromboplastin time suggested delayed initiation of coagulation. NATEM maximum clot firmness (MCF) and fibrin-based thromboelastometry test (FIBTEM ® )-MCF decreased significantly from baseline until the last time point (from 64.6 ± 7.8 and 35.1 ± 12.8 mm to 52.8 ± 4.6 and 21.4 ± 11.8 mm, respectively; P = 0.01 for both parameters). A sharp, transient increase of t-PA had no effect on maximum lysis in the NATEM test. PAI-1 increased significantly 3 h after the start of LPS infusion, paralleled by a decrease in maximum lysis. In conclusion, TEM was superior to standard coagulation tests in reflecting initial activation of coagulation during endotoxinemia. TEM further suggested consumption of coagulation substrate; at the same time, inhibition of plasminogen activation was accompanied by improved clot stability. Further investigations are necessary to establish the clinical relevance of these findings.

The absorption, elimination and metabolism of 14C-trichloroethylene (Tri) was studied in adult female Wistar rats and NMRI mice after administration of 200, 20 and 2 mg/kg Tri. Dose-dependent biotransformation of Tri to metabolites was observed in both species. Induction of hepatic mono-oxygenases by phenobarbital or polychlorinated biphenyls resulted in a higher rate of biotransformation after a single oral dose of 200 mg/kg 14C-Tri to rats. An increase in radioactivity covalently bound to liver and kidney macromolecules of induced rats as compared to control rats parallels the toxic effects of Tri on these organs after induction of cytochrome P-450. The urinary metabolites were analysed by h.p.l.c. In both species, 1,1,1-trichlorocompounds (trichloroacetic acid, trichloroethanol and its glucuronide, comprising 88.9-93.5% of the radioactivity excreted in the urine) constituted the main metabolites; in addition, N-(hydroxyacetyl)-aminoethanol (4.1-7.2%), dichloroacetic acid (0.1-2.0%) and oxalic acid (0.7-1.8%) were identified. The pattern of metabolites in the 72 h urine remained constant for each species in the dose range studied and no change was induced by pretreatment. The percentage of radioactivity exhaled as 14CO2 increased with dose in mice, which may indicate dose-dependent formation of dichloroacetic acid and saturation of deactivating mechanisms for reactive intermediates in mice.

This text covers the field of steady-state kinetics from basic principles to the control of the multi-enzyme systems which constitute metabolic pathways. Emphasis is placed on the interpretation of the kinetic behaviour of enzyme-catalyzed reactions in terms of mechanisms. Algorithms are developed which can be implemented in computer programs for the derivation of equations. The treatment of steady-state enzyme kinetics is extended to allosteric enzymes and subunit interactions in polymeric enzymes. Principles are presented which provide for mathematical analysis of the control of multi-enzyme systems. Problems are included at the end of each chapter and their solutions are found at the end of the book. This book will be a useful text for advanced undergraduates and graduate students taking courses in enzyme chemistry and enzyme kinetics.

1. A computer programme is described which simulates energy metabolism in the whole animal. Simulation was based on representation of the animal as a quasi-steady-state system. 2. Input for the programme consisted of the chemical composition of the diet and an estimate of either the maintenance energy requirement or an estimate of energy retention. 3. Simulation was performed by estimating the yield of adenosine triphosphate in the major metabolic pathways operative in simple-stomached animals, and on the utilization of adenosine triphosphate in major anabolic processes. 4. Results obtained from simulation were in close agreement with experimental observations reported by McCracken (1975).

An aspect of protein nutrition that has not been resolved in a satisfactory manner is the utilizable energy equivalence of proteins. The existing methods overestimate the utilizable energy of proteins. A more accurate method fo calculating the utilizable energy of proteins is to calculate the moles of adenosine triphosphate formed during the complete oxidation of a given amount of proteins. The moles of adenosine triphosphate formed can be calculated from knowledge of the amino acid composition and knowledge of the metabolic pathway for each amino acid. A computer program is described that provides the bookkeeping required for these calculations. The available energy of a protein is calculated in this computer-based method by adjusting the energy value of the proteins so that it is equivalent to that of carbohydrates and fats in providing the energy for adenosine triphosphate formation. The computer-based method was used to calculate the available energy of a group of proteins of known amino acid composition. The available energy varied from 3.02 keal/g for colagen to 3

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