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Fig. 1. Schematic representation of ProCT and the other CT precursors (CTpr) derived from this prohormone (i.e. NProCT, CT-CCP-I, and CCP-I). The mean.

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Presentation on theme: "Fig. 1. Schematic representation of ProCT and the other CT precursors (CTpr) derived from this prohormone (i.e. NProCT, CT-CCP-I, and CCP-I). The mean."— Presentation transcript:

1 Fig. 1. Schematic representation of ProCT and the other CT precursors (CTpr) derived from this prohormone (i.e. NProCT, CT-CCP-I, and CCP-I). The mean concentrations of these peptides in normal serum is indicated. Note that there is appreciably more free NProCT in the serum than CT(1–32). In sepsis, the principal elevations involve the intact ProCT, free NProCT, and free conjoined CT-CCP-I peptide. Sequencing reveals that in sepsis, the ProCT may lack the first two amino acids of the aminoterminus of the molecule, presumably due to enzymatic hydrolytic aminoterminal truncation (110 ), and perhaps other cleavage forms are present as well (111 ). The comparative extent to which any one of these peptides is increased varies among patients. Levels of the free CCP-I peptide also increase but to a lesser extent. In sepsis, serum CT(1–32) concentrations are undetectable, normal, or only slightly to moderately elevated (data from Ref. 30 ). From: Procalcitonin and the Calcitonin Gene Family of Peptides in Inflammation, Infection, and Sepsis: A Journey from Calcitonin Back to Its Precursors J Clin Endocrinol Metab. 2004;89(4): doi: /jc J Clin Endocrinol Metab | Copyright © 2004 by The Endocrine Society

2 Fig. 2. Receiver operating-curve analysis of serum CTpr for the diagnosis of sepsis in an intensive care unit, as compared with values for circulating C-reactive protein, IL-6, lactate, and pentraxin-3 (PTX-3). The sensitivity of CTpr for the diagnosis of sepsis was 89%, specificity 94%, negative predictive value 90%, and positive predictive value 94% (as assessed by the commercially available LUMItest PCT). However, the other non-CTpr markers were considerably less sensitive and less specific and had relatively poor negative or positive predictive values (modified from Ref. 102 ). From: Procalcitonin and the Calcitonin Gene Family of Peptides in Inflammation, Infection, and Sepsis: A Journey from Calcitonin Back to Its Precursors J Clin Endocrinol Metab. 2004;89(4): doi: /jc J Clin Endocrinol Metab | Copyright © 2004 by The Endocrine Society

3 Fig. 3. Top, Time course in septic pigs showing the changes in mean arterial pressure (MAP). Time point 0 h represents commencement of the fourth hour after induction of sepsis and is the time of infusion of purified nonreactive rabbit antibody to the control group and purified antiporcine ProCT rabbit IgG to the treated group. After time point 0, there is a sharp fall in MAP in the control group, but the MAP of the treated group remains near normal levels. *, Statistically significant data points (P < 0.017; mean ± sem). Bottom, Time course showing the changes in serum creatinine. The graph shows very similar creatinine concentrations before antibody infusion, which is followed by a sharp rise in the control group but with concentrations that remain near normal for the treated group. Other physiologic or metabolic parameters also showed benefits. *, Statistically significant data points (mean ± sem, P < 0.037), which were noted at 2, 4, and 6 h, after which all control animals died (from Ref. 131 ). From: Procalcitonin and the Calcitonin Gene Family of Peptides in Inflammation, Infection, and Sepsis: A Journey from Calcitonin Back to Its Precursors J Clin Endocrinol Metab. 2004;89(4): doi: /jc J Clin Endocrinol Metab | Copyright © 2004 by The Endocrine Society

4 Fig. 4. Exposure of human volunteers to one injection of endotoxin illustrates the differences in the release and subsequent decrease of several humoral markers of critical illness: TNFα, IL-1 receptor antagonist (IL-1ra), IL-6, C-reactive protein (CRP), and CTpr (from Ref. 183 ). From: Procalcitonin and the Calcitonin Gene Family of Peptides in Inflammation, Infection, and Sepsis: A Journey from Calcitonin Back to Its Precursors J Clin Endocrinol Metab. 2004;89(4): doi: /jc J Clin Endocrinol Metab | Copyright © 2004 by The Endocrine Society


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