PMC:29007 / 1142-4464
Annnotations
{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/29007","sourcedb":"PMC","sourceid":"29007","source_url":"http://www.ncbi.nlm.nih.gov/pmc/29007","text":"Introduction\nThere are approximately 400000 cases of sepsis reported each year in \t\t the USA, leading to about 100000 deaths annually [1,2,3]. Indeed, mortality from sepsis in \t\t most series is reported to be between 25 and 40%, with Gram-negative bacteria \t\t being the most commonly encountered pathogens [3,4,5]. The severity of sepsis may \t\t distinguish those who may benefit from therapeutic blockade of their excessive \t\t and maladaptive immune response, from those who may not. Consequently, a \t\t practical way to determine the presence and severity of sepsis is essential. \t\t Although systems of evaluation based on clinical observations and physiologic \t\t parameters are helpful, they have been of limited use for predicting morbidity \t\t and mortality in individuals with inflammatory conditions, especially in \t\t surgical populations [6,7,8,9,10]. An early indicator of tissue injury should improve the \t\t predictive capability of these systems. Although several cytokines have been \t\t proposed as markers of disease severity, they are often transiently elevated, \t\t or detected only in local pools [7]. In this regard, \t\t recent studies in humans have revealed that the prohormone of calcitonin (CT), \t\t procalcitonin (ProCT), as well as its component peptides offer promise of being \t\t early and useful predictive markers of systemic inflammation [11,12,13].\nCT is a neuroendocrine (NE) peptide that was once thought to be \t\t exclusively a hormone of thyroid origin. Its principal function appears to be \t\t the conservation of body calcium stores in certain physiologic states such as \t\t growth, pregnancy and lactation, and the maintenance of bone mineral in \t\t emergency situations by means of attenuation of the activity of osteoclasts \t\t [14]. Further study has revealed that CT is produced \t\t extrathyroidally by NE cells throughout the body, and may have multiple \t\t functions [15,16]. \nCT is initially biosynthesized as a larger ProCT polypeptide which is \t\t subsequently cleaved enzymatically into its components, including the mature, \t\t active hormone (Fig 1). Interestingly, in humans with \t\t severe systemic inflammation, very high serum levels of ProCT and its component \t\t peptides are accompanied by normal or only slightly increased levels of mature \t\t CT [17]. In order to investigate whether serum ProCT \t\t levels might correlate with the severity of illness in sepsis, and thus might \t\t provide a convenient marker, we employed a rodent model of quantifiable \t\t Escherichia coli peritonitis, modified for use in the hamster [18]. This model was then utilized to determine the metabolic \t\t perturbations associated with the procalcitonin peptide levels observed with \t\t sepsis.\nFigure 1 The procalcitonin (ProCT) molecule and its components. AminoproCT \t\t\t\t= amino terminus of procalcitonin; immature CT = the 33 amino acid, \t\t\t\tnon-amidated CT; CCP-I = calcitonin carboxyterminus peptide-I. In normal \t\t\t\tpeople, in addition to the free, active, mature CT, small amounts of ProCT, \t\t\t\taminoproCT, CCP-I, the conjoined CT:CCP-I peptide, and the immature CT \t\t\t\tcirculate [18]. The amino acid sequence of the rat \t\t\t\tmature CT is very similar to that of humans, and the sequence of hamster CT, \t\t\t\talthough not yet known, reveals, by immunoassay studies, a marked homology with \t\t\t\tthe rat.\n\nM","divisions":[{"label":"Title","span":{"begin":0,"end":12}},{"label":"Figure caption","span":{"begin":2707,"end":3321}}],"tracks":[]}