Review article
Pathobiochemistry and clinical use of procalcitonin
Michael Meisner *
Department of Anesthesiology and Intensive Care Medicine,University of Jena,Bachstr 18,D-07743Jena,Germany
Received 14November 2001;received in revised form 22March 2002;accepted 25March 2002
Abstract
Induction of the protein procalcitonin during infection and inflammation was first described approximately 10years ago.A large number of publications,primarily clinical studies,demonstrate the increasing use of procalcitonin in modern clinical practice.However,data on the biological function and origin of procalcitonin is scarce.Findings regarding the possible role and source of procalcitonin in sepsis and infection were recently published,and the pathophysiology of the protein has meanwhile been investigated in various experimental models.Procalcitonin obviously has certain biological functions,and it is also known to be specifically induced.Given the hormonal origin of the mature protein and the inflammation-related functions of its propeptides,some investigators suggest that procalcitonin should be referred to as a ‘‘hormokine,’’although its biological functions should be studied in more detail.This review will survey the data now available in recent publications on the induction,production sources,possible biological functions and clinical uses of procalcitonin.D 2002Elsevier Science B.V .All rights reserved.
Keywords:Sepsis;Inflammation;Infection;Genetics;Biochemical;Metabolism;Calcitonin
1.Introduction
Procalcitonin (PCT)was
first described as a sepsis-induced protein detectable in the plasma of patients with sepsis and infection in the early 1990s [1].Preliminary reports indicated that PCT is mainly induced during severe systemic inflammation caused by bacterial infections,but that PCT concentrations remain low during other types of inflammation (e.g.,viral infections,autoimmune diseases,organ transplant rejection).This was soon confirmed by later studies.The most commonly determined calcitonin precur-sor molecule fragments,procalcitonin (PCT)and its
calcitonin–katacalcin fragments are measured using commercially available assays (BRAHMS,Hennigs-dorf,Germany).These assays use antibodies that bind to the calcitonin–katacalcin amino acid chain of the molecule.In addition to its induction during sepsis and infection,experimental and clinical data also indicate that PCT can be induced by a variety of stimuli including bacterial endotoxins,proinflamma-tory cytokines and triggering events such as trauma or cardiogenic shock.However,the PCT concentration remains low when an infection does not lead to a systemic inflammatory response.Numerous studies clearly demonstrate that PCT is preferentially induced in patients with sepsis,especially in severe sepsis or septic shock,and that patients with systemic inflam-mation of nonbacterial origin generally have low PCT levels.
0009-8981/02/$-see front matter D 2002Elsevier Science B.V .All rights reserved.PII:S 0009-8981(02)00101-8
*
Tel.:+49-3641-933-041;fax:+49-3641-933-256.
E-mail address:michael.meisner@t-online.de (M.Meisner).
https://www.doczj.com/doc/af8212735.html,/locate/clinchim
Clinica Chimica Acta 323(2002)17–29
In addition to its preferential induction during bacterial infection,procalcitonin is also closely related to the severity of systemic inflammation and has a reliable kinetics of induction and elimination.PCT can,therefore,be used to monitor the course of systemic inflammation and guide the physician in therapeutic and diagnostic decision-making.Given these properties,PCT measurement found application in the care of critically ill patients and in numerous intensive care units,since the diagnostic qualities of this parameter are superior to those of conventional markers of inflammation(e.g.,temperature,leukocyte count,C-reactive protein and interleukin-6)in a variety of indications.
Regarding its pathophysiology,information on the biochemical characteristics,induction,biological functions and production sources of calcitonin pre-cursor proteins is scarce.However,new data on the pathophysiology of calcitonin precursor proteins, including PCT,were recently published.
In this review,data on the pathophysiology of PCT and related proteins,including their genetic organisa-tion,transcription,differential splicing,protein syn-thesis and posttranslational modifications,will be presented.In addition,the potential production sour-ces and stimuli,measurement techniques and indica-tions for clinical use of PCT will be summarized and discussed.
2.Induction and synthesis of PCT
2.1.The CAP A protein family
Procalcitonin belongs to a group of related pro-teins,including calcitonin gene-related peptides (CGRP)I and II,amylin,adrenomedullin,calcitonin and its precursors,one of which is procalcitonin. CGRP-I and the mRNA of calcitonin I and II pre-cursors,are encoded on the CALC-I gene on chromo-some11.This gene thus encode calcitonin,PCT-I, PCT-II and its various cleavage products.CGRP-II arises from the CALC-II gene(chromosome11). Adrenomedullin is also encoded on chromosome11, whereas amylin arises from chromosome12(see Ref.
[2]for review).All these proteins are usually secreted. To gain access to the Golgi system,they are initially produced in a pro–pro form consisting of approxi-mately100amino acids.Furthermore,they contain two cysteine residues used to form a disulfide bridge in addition to two protein cleavage sites by which they can be processed to yield approximately35amino acid‘‘core proteins,’’which can be amidated.The cleavage products are biologically active and bind to G-coupled7TM-spanning receptors.However,this has not been confirmed for PCT.Given these common features,members of this group of proteins may be described as the‘‘c alcitonin gene-related peptide-a mylin-(p ro-)calcitonin-a drenomedullin family,’’or the‘‘CAPA protein family.’’
2.2.Differential splicing and mRNA synthesis in various cell types
PCT mRNA is synthesized by the CALC-I gene on chromosome11during sepsis and inflammation.The CALC-I gene is also the source of mature calcitonin in healthy subjects,which is produced by C cells of the thyroid(Fig.1).No other genes are known to produce inflammation-induced PCT.The gene is present in various mammals and other species(e.g.,salmon),but the DNA sequences and amino acids found in these animals are species-dependent(Fig.2).The large degree of conservation of the gene in various species indicates that it may have biologically important functions.The CALC-I gene is not only the source of PCT and calcitonin,but also of other proteins and their fragments.It was one of the first genes in which differential splicing was observed[3].Calcitonin, PCT-I,PCT-II,and calcitonin-gene-related peptide (CGRP)-I are encoded by this DNA sequence.Two types of PCT mRNA are synthesized within PCT-producing cells,resulting in two different proteins, PCT-I and PCT-II,which exhibit differences at eight C-terminal amino acids.Variable quantities of the
two Fig.1.Schematic diagram of preprocalcitonin,procalcitonin and its fragments.AA=amino acids.
M.Meisner/Clinica Chimica Acta323(2002)17–29 18
proteins are synthesized.A commercially available PCT assay (LUMItest R PCT,BRAHMS)detects both types.
As explained above,at least three proteins with different sequences and obviously different functions originate from the CALC-I gene .When proteolytic processing is considered,as many as nine different proteins can arise from the gene.The CALC-I gene is,therefore,an example of how the pluripotentiality of genomic sequences yields a variety of different gene products from only one gene locus.These proteins differ not only with respect to their mRNA splicing and procession,but also with respect to their regu-lation.The type of protein synthesized or processed depends on the individual circumstances,for example,the type of cells involved,the stimulus for cellular activation,and individual susceptibility of various cell types to these stimuli.In thyroid C cells and neuro-endocrine cells,which have a well-defined Golgi apparatus,mature calcitonin is processed and stored in secretory granules [4].Calcitonin is then secreted from these granules in response to hormonal or metabolic stimuli.CGRP is produced by other cells,e.g.,intestinal cells or neurons.Variable quantities of PCT-I and PCT-II mRNA can be detected in different tissues,although only weak extra-thyroidal transcrip-tion of the CALC-I gene occurs in the absence of infection.Consequently,PCT concentrations in the plasma of healthy subjects are very low,usually within the picogram per milliliter range (10–50pg/ml).In human tissues,PCT-I and PCT-II mRNA was found mainly in the liver,but also in other organs like the lung,kidney or testis (Fig.3)[5].In the hamster,it was detected in the lungs of nonseptic controls [6]and in all tissues of septic animals,but the degree of expression varied in the different organs.Low con-centrations were measured in leukocytes and small intestinal tissues,whereas high concentrations were found in the lung,liver,pancreas,colon and other organs [6].Ex vivo stimulation of PCT mRNA production is possible,especially in immunocompe-tent cells.In this connection,a more than 100-fold increase in mRNA levels could be observed in human peripheral mononuclear cells stimulated with
endo-
Fig.2.Amino acid sequence homologies of preprocalcitonin in various species.The signal peptide (position 1–25)is designated using lower case letters and the cleavage site is marked by an arrow.The processed procalcitonin protein is designated using capitals.The two cysteine residues are underlined,and residues identical to the human sequence are set in bold letters,those not identical in light italics.The percentage of amino acid homology relative to the human preprocalcitonin sequence is shown in the box [65].
M.Meisner /Clinica Chimica Acta 323(2002)17–2919
toxin and various proinflammatory mediators [7].In addition to PCT,the mRNAs of other proteins of the calcitonin protein family (e.g.,CGRP-I,CGRP-II and adrenomedullin)are also ubiquitously expressed dur-ing sepsis [8,9].
2.3.Protein modification:disulfide bridges,glycosy-lation and proteolytic procession
Procalcitonin has a characteristic secondary and tertiary protein structure that is modified by posttrans-lational processing.The calcitonin sequence of the protein contains two cysteine molecules that can be covalently joined by a disulfide bridge.Calcitonin also has a disulfide bridge,but it is not crucial for receptor binding [10].Procalcitonin and calcitonin both also have a glycosylation site.Since it is located between the cysteine residues,the site is largely exposed within the molecule.Although still under investigation,protein modification of PCT most likely occurs by glycosylation.Deamidation of the molecule also occurs,and two N-terminal amino acids (Ala–Pro)are removed by the enzyme dipeptidyl peptidase IV (DP IV)or CD26[11].As demonstrated by mass spectroscopy and Edman sequence analysis,PCT is a 3–116amino acid protein detectable in the plasma of patients with thermal injury and sepsis.DP IV is located on renal,epithelial and endothelial cells,and is induced by proinflammatory mediators and endo-toxin.Although the turnover rate of DP IV cleavage is low due to the length of the PCT molecule,a molar excess of the enzyme is present in vivo,resulting in high concentrations of truncated PCT (3–116)in the plasma of patients with severe sepsis.Furthermore,DP IV is known to modify other proteins in which the active form is converted to an inactive form,e.g.,chemokines like granulocyte chemotactic protein-2,macrophage-derived chemokine,etc.[12].Since the exact function of biologically active PCT is not known,it presently is not possible to define the structures necessary to constitute a functionally active molecule.The N-terminal amino acids of calcitonin are obviously important for receptor binding,and truncated calcitonin molecules can also function as antagonists [10].It still is not possible to determine whether recombinant or synthetically derived PCT is functionally active.Recombinant procalcitonin and various synthetic proteins have been investigated in vitro in experimental studies.Most of these studies did not reveal significant activity except for the inhibition of inducible nitric oxide synthase (iNOS)production by PCT [13],or that PCT has some effects on TNF a [30,31].However,PCT was found to have a significant effect on survival and circulation in ham-ster and porcine septic shock models using human purified PCT synthesized from a continuously grow-ing thyroid medullary carcinoma cell line (TT cells)[14,15]
.
Fig.3.Detection of the mRNA of PCT-I,PCT-II and CGRP in nonseptic human tissue.The mRNA content of these tissues was determined by RT-PCR (with kindly permission of Russwurm et al.[5]).
M.Meisner /Clinica Chimica Acta 323(2002)17–29
20
In addition to posttranslational modifications,PCT also undergoes enzymatic cleavage.Since the mole-cule has two main cleavage sites,it breaks down into multiple fragments,which can be detected in plasma. These include the N-terminal aminoprocalcitonin fragment(N-Pro)and the conjoined calcitonin:kata-calcin fragment(calcitonin/calcitonin-carboxypeptide I)(Fig.1),which is also measured as‘‘PCT’’by the commercially available assays.These fragments are present in different concentrations in circulating plasma and septic tissue[1,6,16].In some patients, the plasma levels of the fragments were comparable to those of the whole molecule[2].
2.4.Source of PCT during sepsis and endotoxin shock
PCT mRNA can be detected and stimulated in circulating peripheral monocytes,and PCT can be measured in these cells,also on the protein level,by FACS analysis[7,17].However,leukocytes obviously do not play a major role in PCT production during
sepsis[18].Although the stimulus for induction may not have been sufficient in ex vivo experiments, clinical observations indicate that peripheral mononu-clear cells are not a major source of PCT.Significant quantities of PCT were induced during leukopenia in a patient on immunosuppressants for chemotherapy, while no leukocytes were detectable in visually and automatically analyzed blood smears(Fig.4).The patient in question was treated with a cardiac assist device after acute myocardial dysfunction secondary to viral myocarditis.These findings do not rule out the possibility that other cell types capable of producing PCT or PCT mRNA on the protein level may sub-stantially contribute to in vivo PCT synthesis during sepsis.For example,similar amounts of PCT were detected in the supernatants of peripheral leukocytes and cultured liver sections[19].Since relatively high levels of PCT mRNA have been measured in liver tissue[20],and since the liver produces various proteins including acute phase proteins,we analyzed PCT synthesis in an anhepatic baboon shock model in collaboration with Prof.Dr.H.Redl,Ludwig Boltz-mann Institute,Vienna,Austria.In the baboon PCT is induced within4–6h after hemorrhagic shock,but to a greater extent during endotoxin shock[21].Concen-trations usually range from1to6pg/ml after that. Liver resection was performed in an anesthetized animal,and endotoxin shock was induced.Significant quantities of PCT were not measurable in the anhepatic animal,although clinical symptoms and cytokine lev-els were much higher in this baboon[22].However, further studies are needed to confirm these results.The findings of other studies support the hypothesis of hepatic production of PCT.One group found that PCT concentrations in hepatic venous blood were signifi-cantly higher than those measured in arterial or venous blood several hours after liver surgery[23].Thus,the liver seems to produce substantial amounts of PCT during sepsis and infection.
2.5.Measurement of PCT
Different assays for measurement of PCT(PCT-I and PCT-II)are commercially available.The rights for clinical measurement of calcitonin precursors in vari-ous indications are protected by a patent.The patent holder,BRAHMS,supplies the test kits.These include an immunoluminometric assay(ILMA)(LUMI-test R PCT),an assay based on time-resolved amplified cryptate emission(TRACE)technology(Kryptor R-PCT),and a semi-quantitative rapid test(BRAHMS PCT R-Q).These assays are available as semi-auto-mated manual systems and fully automated stat sys-tems.The test results are available within19
min Fig. 4.Induction of procalcitonin in a patient with peripheral leukopenia.Although the patient had peripheral leukopenia(no leukocytes detectable by conventional methods),significant quanti-ties of PCT were present.The patient,who was placed on an artificial cardiac assist device due to viral myocarditis with prolonged cardiac dysfunction,was leukopenic due to immunosuppressive therapy. The PCT concentration(ng/ml),CRP(mg/dl),leukocyte counts (Gpt/l)and core temperature(j C)are indicated on the y-axis.
M.Meisner/Clinica Chimica Acta323(2002)17–2921
(Kryptor R-PCT)to30min(rapid test BRAHMS PCT R-Q)to1h(LUMItest R PCT).The analytical sensitivity of the quantitative test methods ranges between0.06ng/ml(Kryptor R-PCT)and0.1ng/ml (LUMItest R PCT),the functional assay sensitivity (20%inter-assay variation coefficient)is approxi-mately0.3ng/ml(ILMA),and somewhat less for the Kryptor technology.The LUMItest R PCT utilizes two mouse monoclonal antibodies against human calcito-nin and katacalcin.Kryptor R-PCT is based on a sheep polyclonal anti-calcitonin antibody and a monoclonal anti-katacalcin antibody,which bind either to the katacalcin and the calcitonin sequence of calcitonin precursor molecules.Accordingly,neither the N-ter-minal amino acids of the molecule(aminoprocalcito-nin or‘‘N-pro’’)nor the different amino acids distinguishing PCT-I and PCT-II are required for anti-body binding.These commercially available assays measure PCT-I,PCT-II,and various cleavage products of calcitonin precursor molecules consisting at least of the residues of calcitonin and katacalcin.For research purposes,concentrations of the various cleavage prod-ucts of calcitonin precursor molecules can be measured by HPLC[1,6,24]or by individually designed anti-body systems,e.g.,radioimmunoassay[25].Com-pared to the results obtained using the commercially available kits,the research-related technologies may yield different concentration measurement results for the different calcitonin precursor molecules and—depending on the biochemical properties of each cleavage product—to different normal and patholog-ical ranges for these proteins.Differences in the induction and elimination kinetics may also play a role.However,almost every clinical study described in the literature so far has been conducted using the commercially available,patented antibody systems. Therefore,the related calcitonin precursor concentra-tion measurements,usually summarized as‘‘PCT,’’are comparable among the various studies.
3.Biological functions of PCT
3.1.Functional activity of calcitonin precursor proteins
Various groups have attempted to uncover specific biological functions of PCT,especially immunologic functions.Nonetheless,little is definitely known about the function of PCT except that it has some effect on plasma calcium levels[26–29].PCT may function as a co-factor capable of modulating various effects during endotoxin shock.In vitro experiments have shown that it has a weak influence on cytokine expression.This obviously does not play an important role in vivo,since high concentrations are required for inhibition and the effect is only moderate.TNF-a induction was significantly reduced in the presence of PCT or a C-terminal57amino acid fragment[30,31]. Another effect that may by pathophysiologically more important in vivo was observed in cultured smooth muscle cells.Low or moderately elevated PCT con-centrations significantly suppressed TNF-a and IFN-g-stimulated production of cDNA of iNOS in these cells,but not high concentrations[13].
3.2.In vivo effects of PCT
The results of in vivo experiments in hamster and porcine endotoxin shock models are even more impressive.The investigators used purified PCT from the human medullary thyroid cancer TT cell line or neutralizing antibodies to PCT.The survival rate of hamsters increased significantly when PCT was neu-tralized,but decreased after PCT infusion[14].In a porcine model,PCT neutralization had a significant impact on hemodynamic parameters during experi-mental endotoxin shock[15].Plasma calcium levels also decreased in these animal models during endo-toxin shock.A similar decrease in plasma calcium has been observed in patients with septic shock[26,27,29].
3.3.Possible receptors for calcitonin and precursor proteins
Two groups of receptors of the calcitonin gene family,calcitonin receptors(CR)and calcitonin recep-tor-like receptors(CRLR),may play a role in medi-ating PCT-related functions.Members of the CAPA protein family bind to these receptors with different affinities.Receptor activity-modifying proteins (RAMPs)act on these receptors,altering the specific response of the ligand–receptor complex.The spe-cific cellular phenotype of each cell surface receptor is determined by the type of RAMP present(RAMP-1,2 or3)[32].Since RAMP expression is altered by local
M.Meisner/Clinica Chimica Acta323(2002)17–29 22
and humoral influences,RAMPs modify receptor function according to the actual need.Moreover,the response to peptides of the CAPA protein family varies according to the prevailing conditions[4]. 4.Clinical use of PCT measurement
4.1.Differential diagnosis of bacterial and non-bacterial inflammation
The fact that procalcitonin is induced during sys-temic inflammations of bacterial origin defined as sepsis[33]can be used to discriminate between bacterial and nonbacterial inflammations.A number of studies have been performed to evaluate the poten-tial usefulness of PCT for differential diagnosis of bacterial and nonbacterial inflammations,including bacterial and viral meningitis,bacterial pneumonia and sepsis-induced acute respiratory distress syn-drome(ARDS).Other PCT studies have targeted infections with an unspecific focus, e.g.,fever of unknown origin and infected or sterile necrosis sec-ondary to acute pancreatitis.The main indications for PCT measurement in the diagnosis of infection and the relevant cut-off values are presented in Table1.Beside infectious causes for PCT production,the protein can be induced also by a variety of stimuli of non-infectious etiology(see Section4.4).
Also infections,producing only a few symptoms of systemic inflammation generally do no induce high levels of PCT.This difference can be useful for distinguishing between milder and more severe stages of sepsis(Fig.5)(Table2).Nonetheless,the sensitiv-ity and specificity of PCT for diagnosis of infection or differentiation between sepsis-related and nonsepsis-related systemic inflammatory response syndrome may be low in certain cases.In cardiogenic shock, the early postsurgical period or soon after polytrauma, for example,the noninfectious induction of PCT can limit the specificity of PCT.However,because of the reliable kinetics and relatively low-level induction of PCT under these circumstances,especially when compared to other parameters of inflammation,the conditions can be reliably identified by monitoring the PCT concentrations during the follow-up period[34–36].Some studies have shown that PCT levels are higher in septic shock than in cardiogenic shock,and that PCT levels are higher in infected necrosis than in sterile necrosis secondary to pancreatitis[37,38]. Therefore,PCT can reliably differentiate between bacterial and nonbacterial inflammations,provided
Table1
Procalcitonin measurement for differential diagnosis of inflammations of infectious origin
Diagnosis Cut-off
(ng/ml)Sensitivity/specificity
(%)
Median(*),range mean(+),
S.E.M.for each group
Ref.
Meningitis(bacterial/viral) 1.810054F35(+)(S.E.M.)[57],n=59
1000.32F0.35
0.569 1.75(0.16–60)(*)[58],n=30
1000.24(0.12–0.29)
Pneumonia(bacterial/viral)26310(0.6–21)(*)[59],n=72
960.63(0.01–4.38)
Pneumonia(bacterial/atypical germs)– 1.41(0.05–65)(*)[60],n=36
–0.05(0.05–7.5)
Pancreatitis(infected/sterile necrosis) 1.89428.8(3.1–186)(*)[38]
90 1.0(0.6–1.7)
Septic shock 1.510096F181(+)[37],n=29
72
Invasive versus local bacterial
infection in children
0.899214.45F28(+)[61],n=160
950.35F0.32
0.9093 3.6(0.25–364)(*)[62],n=124
780.4(0.11–43)
The sensitivity and specificity of procalcitonin for diagnosis of severe bacterial infection at various cut-off levels is indicated.The median and range(*)plus the mean and standard error of mean(S.E.M.)(+)for each group and given.
M.Meisner/Clinica Chimica Acta323(2002)17–2923
that certain conditions in which PCT may be induced independent of sepsis and infection are considered.4.2.Assessment of the severity of sepsis and systemic inflammation
An important quality of PCT induction is its close association with the severity of systemic inflammation,which is a definite advantage over other parameters of inflammation (Figs.5and 6).High concentrations of PCT occur during severe sepsis and septic shock,i.e.,when organ dysfunction is present [39–43].Further-more,the kinetics of PCT induction and elimination are very reliable and in a range suitable for clinical meas-urement.It takes only around 6h to detect PCT in plasma after induction using one commercially avail-
able assay (BRAHMS)[44].The plasma elimination half-life of PCT is approximately 25–30h [45,46](Fig.7).The absolute PCT concentration level more closely reflects the severity of systemic inflammation and potentially life-threatening complications than other parameters like cytokines and C-reactive protein (CRP),which may exhibit only intermittent peaks or stable peaks that do not rise once an inflammation becomes more severe (Fig.6)[47].
The rise in PCT concentration in patients with severe sepsis is much greater than in those with SIRS or sepsis alone (Fig.5),as was confirmed in a number of studies [33–37,39,40].The PCT concentration also correlates with the severity of organ dysfunction,as defined by different scoring systems,such as SOFA (sepsis-related organ failure assessment)[48]or APACHE II (acute physiology and chronic health evaluation II)[49](Fig.6).C-reactive protein (CRP),the classical parameter for diagnosis of infec-tion,has certain limitations in this indication.CRP induction and elimination is much slower (up to several days)(Fig.8a and b),and CRP levels may not rise again later if the condition becomes more severe (Fig.6)[35,44,50,38].In septic patients,the CRP levels often are already increased to a certain limit which often will not or cannot be exceeded if the condition becomes more severe since this limit is the upper range of concentrations usually induced.None-theless,in patients with moderate systemic inflamma-tion,CRP may still be more sensitive for the diagnosis of infection and systemic inflammation [43,63].4.3.Monitoring and prognosis
The PCT concentration is closely related to the severity of systemic inflammation,and the kinetics of
Table 2
Procalcitonin concentration (ng/ml)during various stages of systemic inflammation and organ dysfunction,classified according to ACCP/SCCM criteria [33]SIRS
Sepsis
Severe sepsis Septic shock
Ref.0.6F 2.2(n =215) 6.6F 22.5(n =53)35F 68(n =20)[40],n =3371.3F 0.2 2.0F 08.7F 2.539F 5.9[41],n =100ca.0.5F 0.2ca.2F 2ca.18F 10ca.20F 10[43],n =101<0.50.8(median) 4.3(median)[63],n =1903.8F 6.9 1.3F 2.7
9.1F 18.238F 59
[42],n =1013.0(median),
0.7–29.5(range)19.1,2.8–35116.8(0.9–351)sepsis,severe sepsis or septic shock [64],
n =33
–
2.4F 0.537F 16
45F 22
[39],n =
145
Fig.5.Procalcitonin (PCT)concentrations during various severities of sepsis classified according to ACCP/SCCM criteria [39].Error bars indicate standard deviation.
M.Meisner /Clinica Chimica Acta 323(2002)17–29
24
PCT induction and elimination are reliably predict-able.Serial PCT measurement can,therefore,be used to monitor disease activity in patients with sepsis and systemic inflammation.These measurements can serve as an aid in therapeutic and diagnostic deci-sion-making,since a decline or increase in PCT indicates changes in the activity of systemic inflam-
mation that may or may not require modification of the diagnosis or therapy.The course of PCT concen-trations over time is also related to the prognosis of systemic inflammation.Continuously increasing plasma PCT levels usually indicate that the systemic inflammation has not subsided,the infection is not under control and/or the therapeutic measures are not effective.These patients are more likely to have a poorer prognosis [47,66–68].Initially,high PCT concentrations do not necessarily indicate a poor prognosis,especially when the inflammation or under-lying disease responds well to treatment [38].Various studies indicating a connection between PCT levels and the severity of organ dysfunction,outcome and prognosis have been published [47,51,69,70],includ-ing investigations in pediatric patients [52],cardiac surgery patients [34],and malaria patients [53].4.4.Induction of PCT by stimuli other than sepsis and infection
Several conditions in which PCT can be induced independent of sepsis and infection have been described (see Ref.[54]for review).These
include
Fig.7.Temporal course of induction of various inflammatory cytokines,C-reactive protein (CRP)and procalcitonin (PCT)after surgical trauma (thoracic surgery)[44]
.
https://www.doczj.com/doc/af8212735.html,parison of procalcitonin (PCT)and C-reactive protein (CRP)in patients with sepsis and different severities of disease and organ dysfunction classified using the APACHE II and SOFA score [47].*p <0.05(MWU test)compared to previous group.
M.Meisner /Clinica Chimica Acta 323(2002)17–2925
surgery,polytrauma,heat shock,burn injuries,pro-longed cardiogenic shock and severe systemic inflam-mation,e.g.,secondary to multiple organ dysfunction syndrome (MODS).Increased PCT production is also are observed in newborns during the first days after delivery [55].In these patients,PCT is obviously induced by factors other than endotoxins or bacteria,e.g.,high concentrations of proinflammatory cyto-kines,tissue trauma,and poor microcirculatory blood flow.PCT can also be used as a diagnostic parameter in these cases,since its elimination kinetics and possible range of unspecific induction can be pre-dicted (Fig.8a and b).Persistently high or increasing
PCT levels suggest an ongoing systemic inflammatory response or septic complication after surgery [34,56].5.Conclusions
The usefulness of procalcitonin (PCT)as a diag-nostic parameter has been demonstrated in various clinical studies.PCT induction primarily occurs dur-ing systemic inflammations of infectious origin,but has also been observed in etiologies other than infection.The diagnostic capacity of PCT is superior to that of other parameters of infection and inflam-mation in certain indications due to the close corre-lation between the PCT concentration and the severity of systemic inflammation,the preferential induction of PCT during inflammation of bacterial origin,PCT’s high concentration range,especially during the severe stages of sepsis and systemic inflammation,and its reliable kinetics of induction and elimination.Thus,PCT not only supplements the diagnostic information provided by various other parameters of inflammatory response,but also supplies additional information not furnished by conventional parameters of inflammation.Several studies suggest a possible biological function or co-function of procalcitonin during sepsis and endotoxin shock,which cannot be definitively clarified at present.The current hypoth-eses suggest that PCT may alter immunologic func-tions and possibly influence microcirculation and vasomotility.Sufficient quantities of biologically ac-tive test material,definition of specific receptors for PCT,and adequate animal models are needed to de-termine the specific effects of this interesting family of proteins.References
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PCT专利申请简介： PCT专利申请是指专利申请人通过PCT途径递交国际专利申请，向PCT缔约国申请专利。PCT 专利申请大致可分为国际阶段和国家阶段，其中国际阶段由国际受理、国际检索，国际公布、初步审查等步骤，经过国际检索、国际公开以及国际初步审查（如果要求了的话）这一国际阶段之后，专利申请人办理进入国家阶段的手续。国家阶段是国际申请审批程序的第二阶段,国家阶段在申请人希望获得专利权的国家的专利局(称作指定局或选定局)里进行。它包括办理进入国家阶段的手续和在各指定局或选定局里进行的审批程序 PCT专利申请优缺点： ①PCT专利申请优点 （1）简化PCT专利申请程序，一份申请,以一种语言（中文活英文）撰写文件，像一个专利受理局提出申请，在进入国家阶段前，可代替多份外国申请。 （2）准备时间充足，进入PCT国际阶段后，申请人会收到国际检索报告，申请人可据此初步判断自己的专利申请的授权前景，然后可根据需要自优先权日起30个月内进入某一个或者某几个国家进行PCT国家阶段的审查。 （3）在完成国际阶段后，进入国家阶段前，可根据初步审查报告，修改申请文件，准备高质量的译文供国家阶段使用。 （4）提高国际竞争力。一旦通过PCT申请获得指定国家的专利授权，企业便可以大大提高在相关国家的竞争力，同时可以有效提升企业的国际形象。 ②PCT专利申请缺点 （1）PCT专利申请只包括发明和实用新型专利，外观设计专利不能通过PCT途径申请。（2）PCT专利申请与巴黎公约相比，由于多了国际阶段，因此费用更高（部分国家PCT申请比普通申请便宜）、花费时间更长 PCT专利申请注意事项： （1）是否PCT申请成功获专利,则在指定缔约国公开,并受保护,未指定的缔约国不公开也不受保护？ 首先，PCT国际申请是自优先权日起18个月，由国际局进行国际公布的，因此不存在在某些国家公开，在某些国家不公开的情况。 其次，根据2004年修改的细则，目前PCT申请提交时自动全部指定所有指定国。除非在国际申请提交后特别排除某些指定国，否则PCT申请自国际申请之日起，即在所有指定国享有一般国家专利申请的法律效力。 最后，PCT只是一个专利申请程序，而不是专利授予程序，最后的授权决定是由各个指定局作出的。故只有在指定局获得授权，才能够获得专利权的保护。 （2）PCT申请提交的申请文件种类？ 提交PCT国际申请时，需要提交的申请文件包括：请求书（PCT/RO/101表格）、说明书、权利要求书、摘要、附图、如果申请涉及氨基酸/核苷酸序列，还应包含氨基酸/核苷酸序列表、委托书等。 （3）PCT专利是否与国内专利有冲突 我司于2007年5月申请国内专利，公布日为2008年4月，但我司客户就同一产品申请了PCT专利，申请时间为2006年1月，公布日为2008年8月，请问这两份专利是否有冲突，我司专利是否无效？我司是否可以在其它国外市场使用？ 上述问题会产生三种情况：
PCT检测与临床意义 1简介 PCT是血清中存在的无激素活性的降钙素（calcitonin，CT）前肽物质，是由116个氨基酸组成、相对分子量为13000KD的糖蛋白。PCT的体内半衰期为25－30h。正常情况下，PCTmRNA在甲状腺滤泡旁细胞粗面内质网内翻译成含141个氨基酸残基的前PCT，分子质量约为16000KD，包括N端84个氨基酸（含25个氨基酸的信号肽）、活性CT（32肽）和下钙素（katacalcin，21肽）三部分，前两部分由2肽（-Lys-Arg-）连接，后两部分被4肽 （-Gys-Lys-Lys-Arg-）隔开。前PCT进入内质网膜，经糖基化和特异性酶切除N-末端的信号肽，生成含116个氨基酸残基的PCT，后依次经不同的蛋白水解酶酶解，先切除含1-57氨基酸残基的N端肽（N-PCT），最后酶解生成T和下钙素。 2．PCT检测原理 PC测定结合一步免疫夹心法和最后的酶联荧光分析（ELEA）。在分析固相包被针（SPR）既起移液装置的作用外，又起固相作用。测试时，仪器将样本滴入包含被碱性磷酸酶标记的抗体结合孔中。样本偶联物进出SPR循环多次，使PCT结合固定在涂有单克隆鼠抗降钙素原免疫球蛋白的SPR内，与免疫球蛋白偶联形成三明治.末结结合合部分在清洗步骤中被洗去，然后执行两个检测步骤，在每步中，底物4－甲基伞形酮酰磷酸脂循环进入SPR，酶将底物水解为荧光物质，在450nm处可被测出，荧光强度和样本中抗原的浓度成正比。根据定标曲线可得出样本中PCT的浓度。 3．PCT试剂条说明
4.PCT的测量方法及参考范围 曾用放射免疫分析法（RIA）和夹心免疫放射分析法对血浆PCT进行测定，虽然灵敏度较高，但放射性元素的污染致使此方法使用受限。近来PCT的检测方法已改进为双抗夹心免疫发光法。此方法可排除交叉反应；提高特异性，同时也有很高的灵敏度（0.lug/L）。健康人血浆PCT含量极微（<0.1ug/L）。 0.5ug/L被认为是感染性疾病诊断的分界值。但值得注意的是，新生儿出生后两天内血浆PCT生理性升高，最高达21ug/L，3 d后很快下降至成人水平。因此对新生儿而言，要求建立年龄依赖性参考值。有文献报道通过受试者工作特性曲线（ROC）统计分析，报道在出生后第一天内对新生儿全身严重细菌和真菌感染辅助诊断的PCT分界值为1.5ug/L，第二天的分界值为10ug/L。不同疾病患者血浆PCT的浓度水平见下表。 表1 不同人血浆PCT的医学决定水平
PCT 检测与临床意义 1简介 PCT 是血清中存在的无激素活性的降钙素（calcitonin ，CT ）前肽物质，是由116个氨基酸组成、相对分子量为13000KD 的糖蛋白。PCT 的体内半衰期为25－30h 。正常情况下，PCTmRNA 在甲状腺滤泡旁细胞粗面内质网内翻译成含141个氨基酸残基的前 PCT ，分子质量约为 16000KD ，包括N 端84个氨基酸（含25个氨基酸的信号肽）、活性CT （32肽）和下钙素（katacalcin ，21肽）三部分，前两部分由2肽（-Lys-Arg-）连接，后两部分被 4肽 （-Gys-Lys-Lys-Arg-）隔开。前PCT 进入内质网膜，经糖基化和特异性酶切除N-末端的信号肽，生成含116个氨基酸残基的PCT ，后依次经不同的蛋白水解酶酶解，先切除含1-57氨基酸残基的N 端肽（N-PCT ），最后酶解生成T 和下钙素。 2．PCT 检测原理 PC 测定结合一步免疫夹心法和最后的酶联荧光分析（ELEA ）。在分析固相包被针（SPR ）既起移液装置的作用外，又起固相作用。测试时，仪器将样本滴入包含被碱性磷酸酶标记的抗体结合孔中。样本偶联物进出SPR 循环多次，使PCT 结合固定在涂有单克隆鼠抗降钙素原免疫球蛋白的SPR 内，与免疫球蛋白偶联形成三明治.末结结合合部分在清洗步骤中被洗去，然后执行两个检测步骤，在每步中，底物4－甲基伞形酮酰磷酸脂循环进入 SPR ，酶将底物水解为荧光物质，在450nm 处可被测出，荧光强度和样本中抗原的浓度成正比。根据定标曲线可得出样本中PCT 的浓度。 3．PCT 试剂条说明
4.PCT的测量方法及参考范围 曾用放射免疫分析法（RIA）和夹心免疫放射分析法对血浆PCT进行测定，虽然灵敏度较高，但放射性元素的污染致使此方法使用受限。近来PCT的检测方法已改进为双抗夹心免疫发光法。此方法可排除交叉反应；提高特异性，同时也有很高的灵敏度（0.lug/L）。健康人血浆PCT含量极微（<0.1ug/L）。 0.5ug/L被认为是感染性疾病诊断的分界值。但值得注意的是，新生儿出生后两天内血浆PCT生理性升高，最高达21ug/L，3 d后很快下降至成人水平。因此对新生儿而言，要求建立年龄依赖性参考值。有文献报道通过受试者工作特性曲线（ROC）统计分析，报道在出生后第一天内对新生儿全身严重细菌和真菌感染辅助诊断的PCT分界值为1.5ug/L，第二天的分界值为10ug/L。不同疾病患者血浆PCT的浓度水平见下表。 表1 不同人血浆PCT的医学决定水平
第一章概论 一、项目概况 （一）项目名称 PCT项目 （二）项目选址 xx经济示范区 项目选址应符合城乡建设总体规划和项目占地使用规划的要求，同时具备便捷的陆路交通和方便的施工场址，并且与大气污染防治、水资源和自然生态资源保护相一致。 （三）项目用地规模 项目总用地面积54974.14平方米（折合约82.42亩）。 （四）项目用地控制指标 该工程规划建筑系数56.51%，建筑容积率1.56，建设区域绿化覆盖率7.13%，固定资产投资强度187.28万元/亩。 （五）土建工程指标 项目净用地面积54974.14平方米，建筑物基底占地面积31065.89平方米，总建筑面积85759.66平方米，其中：规划建设主体工程54602.13平方米，项目规划绿化面积6112.61平方米。 （六）设备选型方案
项目计划购置设备共计146台（套），设备购置费5358.65万元。 （七）节能分析 1、项目年用电量859631.79千瓦时，折合105.65吨标准煤。 2、项目年总用水量19091.26立方米，折合1.63吨标准煤。 3、“PCT项目投资建设项目”，年用电量859631.79千瓦时，年总用 水量19091.26立方米，项目年综合总耗能量（当量值）107.28吨标准煤/年。达产年综合节能量39.68吨标准煤/年，项目总节能率26.98%，能源利用效果良好。 （八）环境保护 项目符合xx经济示范区发展规划，符合xx经济示范区产业结构调整 规划和国家的产业发展政策；对产生的各类污染物都采取了切实可行的治 理措施，严格控制在国家规定的排放标准内，项目建设不会对区域生态环 境产生明显的影响。 （九）项目总投资及资金构成 项目预计总投资17906.69万元，其中：固定资产投资15435.62万元，占项目总投资的86.20%；流动资金2471.07万元，占项目总投资的13.80%。 （十）资金筹措 该项目现阶段投资均由企业自筹。 （十一）项目预期经济效益规划目标
2012降钙素原(PCT)急诊临床应用的专家共识 (2013-04-26 14:25:49)转载▼ 分类：专家共识 标签：pct 降钙素原 临床应用 专家共识 2012降钙素原(PCT)急诊临床应用的专家共识 降钙素原急诊临床应用专家共识组 感染性疾病是急诊科常见的疾病之一，由感染引起的全身炎症反应综合征是脓毒症最根本的病理生理学改变。由于全身炎症反应的复杂性，至今尚无理想的诊断、分层、预后工具和效果显著的治疗方案。已有不少研究证实，脓毒症早期的病理生理改变是功能性的、可逆的。因此，早期准确地诊断脓毒症并监测是改善预后的决定性因素之一。降钙素原(proealeitonin, PCT)与感染和脓毒症的相关性很好，经过近20年的研究和实践，已经被推荐用于细菌感染性脓毒症的诊断、分层、治疗监测和预后评估。 1 PCT简介 1．1 PCT主要的生物学效应 PCT的生物学效应目前尚无明确的结论，主要的生物学效应有：次级炎症因子的作用、趋化因子的作用、抗炎和保护作用。 1．2 PCT的检测方法和稳定性 目前PCT可通过半定量和定量方法检测。半定量方法有胶体金标志检验，定量方法包括放射免疫分析法、免疫荧光法、双抗夹心免疫
化学发光法、酶免法等。 PCT在血样中非常稳定，采血后在室温下放置24h，PCT质量浓度仅下降12％左右，如果在4。C保存仅下降6％。冰冻、抗凝剂、血清或者血浆、动脉血或者静脉血对检测结果的影响均微乎其微。如果需要长时问存放后检测，则需要低温或者冰冻保存血样。 1．3 PCT的正常值及参考范围 健康人的血浆PCT质量浓度低于0．05 ng／ml。老年人、慢性疾病患者、以及不足10％的健康人血浆PCT质量浓度高于0．05 ng／ml，最高可达0．1 ng／ml，但一般不超过0．3 ng／ml。脓毒症患者PCT的诊断界值为超过0．5 ng／ml，严重脓毒症和脓毒性休克患者PCT质量浓度波动在5～500 ng／ml之间。极少数严重感染患者血浆PCT水平超过1000 ng／ml。 PCT质量浓度的临床意义和处置建议见表1。 PCT质量浓度 (ng/ml) 临床意义处置建议 <0．05正常值- <0．5无或轻度全身炎症反 应。可能为局部炎症或 局部感染 建议查找感染或者其他导 致PCT增高的病因。 0 5～2中度全身炎症反应可能 存在感染，也可能是其 他情况，如严重创伤、 大型手术、心源性休克。 建议查找可能的感染因 素。如果发现感染，建议 6-24 h后复查PCT。
PCT树脂简介 材料简介 PCT是聚对苯二甲酸1,4-环己烷二甲醇酯的简称，也称聚对苯二甲酸环己撑二亚甲基酯树脂。PCT树脂是一种耐高温、半结晶型的热塑性塑料，系聚酯家族又一新品， PCT 树脂由1,4-环己烷二甲醇(简称CHDM)和对苯二甲酸二甲酯(简称DMT)聚合而成。。 特性用途 PCT作为聚酯家族的一种新品种，其性质与聚对苯二甲酸乙二醇酯(PET)和聚对苯二甲酸丁二酯(PBT)相似，具有PBT的强度、韧性，而耐热性优于PET。PCT具有较高的耐热性，其连续应用温度范围在130℃~150℃之间，挠曲温度为243℃~260℃，可以代替耐热级的PBT用作印刷电路板生产中的波峰焊接板和回流焊接板。 由于PCT还具有良好的韧性、热稳定性、易加工性、耐化学性和低吸湿性，在潮湿条件下，对PCT的机械性能、尺寸稳定性和加工性能的影响很小。因此，PCT可以与PPS、LCPS和高温聚酰胺等许多聚合物竞争。 PCT对清洗用的溶剂，如丙酮、甲乙酮、乙醇和芳香溶剂等，有很好的耐化学性能。 PCT及其改性产品可应用的领域如下： (1)电器/电子： PCT填充共混物用于接线盒、插座、集成电路板、插头槽板组合件、继电器元件，线圈架和无线通讯设备元件。发展趋势是小型化和在表面加工技术辅助设备中应用。如在高温装配过程蒸气相和红外线焊接等加工技术装备中应用。传统的设备罩盖材料正被高温材料如PCT所取代。 (2)汽车： 由于PCT共混物的耐高温性、高强度和耐化学性，它用于各种汽车发动机室机械元件如交流发电机电枢和压敏器。 (3)医药器械： 共聚酯和熔体共混物具有透明度高、韧性好、耐化学性和耐辐射性，因此它们应用于各种医药器械，如导管系统、细菌过滤器、自密封水价、通风管道系统的一次使用零件和医用接管头。 (4)仪表器械： 纯色和染色的共聚酯及熔体共混物应用于仪表器械，如底板维护喷嘴、液体储存槽和冰箱门和其它透明内部零件。从经济角度，这些聚合物提供的透明度、韧性和耐化学性在一定范围内不需再用其它的透明聚合物。新的、透明的PCT聚合物的特点是能制造较高级模件，同时价格较低，使其成为仪表产品材料中的最新附加物。 (5)光学元件： 共聚物和熔体共混物可应用于那些要求透明度和高抗冲击性的地方，包括安全护目镜、安全玻璃框、脸部防护罩、太阳镜和牙齿保护套等。 (6)游乐/专用车辆： 由于它们的抗冲击性、耐化学和抗UV性、光泽度和可染色性。在这些交通工具应用中包括割草机盖板和侧板。拖拉机发动机盖、护栅和挡泥板等。
PCT简介 1、什么是PCT？ 从名称上可以看出，专利合作条约是专利领域的一项国际合作条约。自采用巴黎公约以来，它被认为是该领域进行国际合作最具有意义的进步标志。但是，它主要涉及专利申请的提交，检索及审查以及其中包括的技术信息的传播的合作性和合理性的一个条约。 PCT不对“国际专利授权”：授予专利的任务和责任仍然只能由寻求专利保护的各个国家的专利局或行使其职权的机构掌握（指定局）。PCT并非与巴黎公约竞争，事实上是其补充。的确，它是在巴黎公约下只对巴黎公约成员国开放的一个特殊协议。 2、PCT的历史： 为了克服传统体系中出现的问题，保护工业产权国际（巴黎）联盟执行委员会于1966年9月邀请BIRPI（世界知识产权组织的前身）立即研究一个解决办法以减少申请人和专利局所作的重复工作。1967年国际条约草案由BIRPI起草并提交专家委员会。此后几年一些旨在修改草案的会议如期举行，并于1970年6月在华盛顿举行了外交会议，此次会议制定了专利合作条约。专利合作条约或称PCT于1978年1月24日生效，并于1978年6月1日在最初的18个缔约国开始实施。截止至2009年11月，该条约已拥有142个成员国。此增长表明各国对实施该条约的浓厚兴趣。另据WIPO的PCT年报统计，2008年国际局共收到163，600件国际申请，比前一年增长了2.3%。 对PCT的进展所给出的上述简介说明，在今后将有越来越多的国家，发展中或发达国家成为PCT的成员国，同时，申请数量已表明，PCT的应用将继续不断地增加。 PCT对进入国家阶段手续的规定 1、缴纳国家费用： 申请人履行进入国家阶段的手续之一是缴纳国家费用，主要是指申请费，有些国家称为基本国家费。 2、提交国际申请译文： 如果国际申请提出时使用的语言或者国际公布时使用的语言不是指定局的官方语言，则为进入该国国家阶段需要提交国际申请译成指定局所要求语言的译文。 3、提供国际申请副本和发明人信息： 如果指定局尚未收到国际局向该局传送的国际申请，则可以要求申请人提供国际申请的副本。
. .' PCT树脂简介 材料简介 PCT是聚对苯二甲酸1,4-环己烷二甲醇酯的简称，也称聚对苯二甲酸环己撑二亚甲基酯树脂。PCT树脂是一种耐高温、半结晶型的热塑性塑料，系聚酯家族又一新品， PCT 树脂由1,4-环己烷二甲醇(简称CHDM)和对苯二甲酸二甲酯(简称DMT)聚合而成。。 特性用途 PCT作为聚酯家族的一种新品种，其性质与聚对苯二甲酸乙二醇酯(PET)和聚对苯二甲酸丁二酯(PBT)相似，具有PBT的强度、韧性，而耐热性优于PET。PCT具有较高的耐热性，其连续应用温度范围在130℃~150℃之间，挠曲温度为243℃~260℃，可以代替耐热级的PBT用作印刷电路板生产中的波峰焊接板和回流焊接板。 由于PCT还具有良好的韧性、热稳定性、易加工性、耐化学性和低吸湿性，在潮湿条件下，对PCT的机械性能、尺寸稳定性和加工性能的影响很小。因此，PCT可以与PPS、LCPS和高温聚酰胺等许多聚合物竞争。 PCT对清洗用的溶剂，如丙酮、甲乙酮、乙醇和芳香溶剂等，有很好的耐化学性能。 PCT及其改性产品可应用的领域如下： (1)电器/电子： PCT填充共混物用于接线盒、插座、集成电路板、插头槽板组合件、继电器元件，线圈架和无线通讯设备元件。发展趋势是小型化和在表面加工技术辅助设备中应用。如在高温装配过程蒸气相和红外线焊接等加工技术装备中应用。传统的设备罩盖材料正被高温材料如PCT所取代。 (2)汽车： 由于PCT共混物的耐高温性、高强度和耐化学性，它用于各种汽车发动机室机械元件如交流发电机电枢和压敏器。 (3)医药器械： 共聚酯和熔体共混物具有透明度高、韧性好、耐化学性和耐辐射性，因此它们应用于各种医药器械，如导管系统、细菌过滤器、自密封水价、通风管道系统的一次使用零件和医用接管头。 (4)仪表器械： 纯色和染色的共聚酯及熔体共混物应用于仪表器械，如底板维护喷嘴、液体储存槽和冰箱门和其它透明内部零件。从经济角度，这些聚合物提供的透明度、韧性和耐化学性在一定范围内不需再用其它的透明聚合物。新的、透明的PCT聚合物的特点是能制造较高级模件，同时价格较低，使其成为仪表产品材料中的最新附加物。 (5)光学元件： 共聚物和熔体共混物可应用于那些要求透明度和高抗冲击性的地方，包括安全护目镜、安全玻璃框、脸部防护罩、太阳镜和牙齿保护套等。 (6)游乐/专用车辆： 由于它们的抗冲击性、耐化学和抗UV性、光泽度和可染色性。在这些交通工具应用中包括割草机盖板和侧板。拖拉机发动机盖、护栅和挡泥板等。
PCT(降钙素原)快速定量测定 降钙素原(PCT)是降钙素(Calcltonin，CT)的前体，主要在甲状腺滤泡旁细胞内合成，是由116个氨基酸组成的糖蛋白。它可以在酶的作用下逐步裂解成57个氨基酸的氨基PCT，32个氨基酸的CT和21个氨基酸的降钙蛋白。当感染发生时，血液中的PCT浓度在2-6小时内迅速升高。 降钙素原检测是一种评价细菌感染的最新替代指标，是用于细菌感染/脓毒症鉴别诊断、严重程度判断、治疗监测、预后评估及抗生素管理使用的具有创新意义的诊断指标。健康人血浆PCT含量极低。 与其他细菌感染的传统诊断指标如白细胞计数、血沉、C-反应蛋白、细菌培养等比较，PCT拥有早期、快速、更高的灵敏度和特异性，从临床应用鉴别诊断中可知，PCT在细菌感染特别是脓毒症方面的诊断的特异性明显由于传统诊断指标，目前在国外已广泛应用于临床各科室。具体应用如下： 一、检测降钙素原（PCT）避免滥用抗生素 抗生素可抑制细菌感染，但对病毒感染却无效，反而可能引发病人体内的抗药性及不良反应。 二、细菌感染早期的鉴别诊断 通常在发生细菌感染后2-6小时快速升高，并可检测到；对细菌感染的诊断特异性在90％左右，而在病毒感染、自身免疫性疾病、慢性非特异性炎症等情况下几乎不升高。 三、与感染病情的严重程度与发展呈正相关 随着感染严重程度的增加，PCT浓度明显增高，尤其对严重脓毒症和脓毒性休克的诊断特异性明显高于WBC、CRP等指标，国外某些文献指出其特异性甚至可达到100％，因此PCT浓度测定 四、细菌感染治疗效果及预后观察 PCT水平的下降表明炎性反应的降低及感染灶的清除，因此可提示良好的预后及治疗效果观察，与疾病的发展呈现正相关。