Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Procalcitonin (PCT) is one of the precursors in the synthesis of calcitonin in thyroidal C-cells and other neuroendocrine cells. PCT, among other calcitonin precursors, is elevated in the serum of many conditions associated with a systemic inflammatory response syndrome, even in the absence of the thyroid gland. The aim of our study was to identify PCT-producing extrathyroidal tissues in primate sepsis. In order to induce PCT production, we treated four olive baboons ( papio cynocephalus anubis) with the endotoxin lipopolysaccharide (LPS) from s. typhimurium. We found an increase in serum PCT 3 to 5 hours after LPS injection to levels of 0.2 ng/ml, attaining a peak above 4 ng/ml PCT at 10 hours. In contrast, the untreated baboon had no detectable circulating PCT in the serum. In one animal, additional LPS boosting after 24 hours did not increase serum PCT further. Soluble proteins were extracted from different organs, fractionated by C18 extraction, and PCT was measured in an immunoluminometric assay (ILMA), which was specifically developed for this study. PCT concentrations above 0.2 ng/g of wet tissue were found in a variety of organs in LPS treated baboons, but not in the control baboon. Organs and tissues with the highest PCT concentration included liver, kidney, aorta, fat, ovaries, bladder and adrenal gland. RT-PCR confirmed an extrathyroidal origin of PCT. Importantly, CT-mRNA expression was found in liver, lung, kidney, adrenal, colon, skin, spleen, brain and pancreas. In conclusion, our data confirm previous findings in hamsters, indicating an extrathyroidal origin for PCT in sepsis. Our primate model offers a valuable tool for further investigation of PCT's pathophysiological role and its immunoneutralization as a therapy for sepsis.
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PMID:Production of procalcitonin (PCT) in non-thyroidal tissue after LPS injection. 1291 98

Circulating levels of calcitonin precursors (CTpr), including procalcitonin (ProCT), increase up to several thousand-fold in human sepsis, and immunoneutralization improves survival in two animal models of this disease. Herein, we analyzed inflammation-mediated calcitonin I gene (CALC I) expression in human adipocyte primary cultures and in adipose tissue samples from infected and noninfected patients with different levels of serum ProCT. In ex vivo differentiated adipocytes, the expression of CT mRNA increased 24-fold (P < 0.05) after the administration of Escherichia coli endotoxin (lipopolysaccharide) and 37-fold (P < 0.05) after IL-1beta administration by 6 h. ProCT protein secretion into culture supernatant increased 13.5-fold (P < 0.01) with lipopolysaccharide treatment and 15.2-fold (P < 0.01) with IL-1beta after 48 h. In coculture experiments, adipocyte CT mRNA expression was evoked by E. coli-activated macrophages in which CT mRNA was undetectable. The marked IL-1beta-mediated ProCT release was inhibited by 89% during coadministration with interferon-gamma (IFNgamma). In patients with infection and markedly increased serum ProCT, CT mRNA was detected in adipose tissue biopsies. Hence, we demonstrate that ProCT, which is suspected to mediate deleterious effects in sepsis and inflammation, is a novel product of adipose tissue secretion. The inhibiting effect of IFNgamma on IL-1beta-induced CT mRNA expression and on ProCT secretion might explain previous observations that serum ProCT concentrations increase less in systemic viral compared with bacterial infections.
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PMID:In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue. 1296 10

The sepsis is a bacterial invasion of the organism producing many manifestations which are able to amplify themselves. In the United States of America there are 100,000 death per year and the incidence is among 300,000-500,000 cases. The major surgery in the elder (especially if it is in emergency) has a great percental of risk because the preoperative study isn't often complete. Fever, agitation, panting, bullation, abdominal splinting, enteroplegia, are signals of evolving inflammatory situation. Moreover there are disorders of biochemical values: leukocytosis, thrombocytopenia, increased levels of VES, PCR, amylase and biliribinaemia. The more common radiological examinations are the straight radiography of abdomen and horax, abdomen ultrasonography, CT or MRI. In the last years pro-calcitonin, interleukin-6 , C-reactive protein, and nitric oxide from endothelial and muscularis cells have been evaluated as prognostic factors in the septic shock.
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PMID:[Septic shock: surgical and medical problems in the elderly]. 1467 79

Prior studies have demonstrated that the prohormone, procalcitonin (ProCT), and its component calcitonin precursors (CTpr) are increased in the serum of septic patients, correlate with the severity of the illness, and persist for relatively long periods of time. Animal studies in septic hamsters have revealed that the administration of ProCT is toxic and that immunoneutralization with IgG that is reactive to this molecule significantly improves survival. A large animal model of a very rapidly lethal polymicrobial sepsis has been developed in the pig in order to measure continuous physiological and metabolic parameters and also to compare the effects in this animal of an immunoneutralization, which is performed late in the course of the disease, to an identical, but early, therapy. Based upon the physiological and metabolic parameters, the late therapy, which was initiated during the fourth hour at a time when pigs were nearly moribund, was found to be as beneficial as early therapy. In both late and early therapy, the only animals to survive at the predetermined time of euthanasia were those which had received immunoneutralization therapy.
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PMID:Immunoneutralization of procalcitonin as therapy of sepsis. 1473 23

Sepsis is a complex syndrome characterized by simultaneous activation of inflammation and coagulation in response to microbial insult. These events manifest as systemic inflammatory response syndrome (SIRS)/sepsis symptoms through release of proinflammatory cytokines, procoagulants, and adhesion molecules from immune cells and/or damaged endothelium.Conventional treatments have focused on source control, antimicrobials, vasopressors, and fluid resuscitation; however, a new treatment paradigm exists: that of treating the host response to infection with adjunct therapies including early goal directed therapy, drotrecogin alfa (activated), and immunonutrition. The multimechanistic drotrecogin alfa (activated) has been shown to reduce mortality in the severely septic patient when combined with traditional treatment. Therapies targeting improved oxygen and blood flow and reduction of apoptosis and free radicals are under investigation. Early sepsis diagnosis through detection of pro calcitonin, C reactive protein, sublingual CO2, and genetic factors may be beneficial. Ultimately, intervention timing may be the most important factor in reducing severe sepsis mortality.
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PMID:The puzzle of sepsis: fitting the pieces of the inflammatory response with treatment. 1476 63

Despite advances in the diagnosis and treatment of infections diseases, sepsis and ensuing multiorgan failure are the major causes of morbidity and mortality in the intensive care units. Such manifestations of systemic inflammation as fever, leukocytosis, tachycardia, etc. may be noninfectious in origin and are neither specific nor sensitive for sepsis. Procalcitonin is a new potential marker for detection of bacterial, fungal and protozoal infections. Procalcitonin, a propeptide of calcitonin, is normally produced in the C-cells of the thyroid gland. Procalcitonin is a polypeptide consisting of 116 amino acids and with a molecular weight of about 13 kDa. During severe systemic infections it is produced by extrathyroidal tissues. Procalcitonin can be put to immediate use in both diagnostic and therapeutic decision-making. This review article discusses biology of procalcitonin, its laboratory determination, usage as an indicator for severe infection and sepsis, and comparison with circulating cytokines in severe infection. It also reviews value of procalcitonin in differentiation of infectious vs non-infectious inflammatory host response, possible elevation of procalcitonin in the absence of infection, its use for differentiation of viral and non-viral infections and as marker for prognosis and evaluation of therapy. Specific indications for determination of procalcitonin are also discussed.
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PMID:[Procalcitonin as a marker of the systemic inflammatory response to infection]. 1525 37

Procalcitonin (PCT), a protein of 116 amino-acids was discovered as a prohormone of calcitonin produced by C-cells of the thyroid gland and intracellularly cleaved by proteolytic enzymes into the active hormone. Circulating levels of PCT in healthy subjects are below detection limit. Blood concentrations of procalcitonin are increased in systemic inflammation, especially when this is caused by bacterial infection. Studies of its behaviour in patients with bacterial sepsis have led to the proposal that it may be a useful marker of systemic bacterial infection, with greater specificity and sensitivity than acute phase proteins such as C-reactive protein.
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PMID:Structure and diagnostic value of procalcitonin. 1531 11

We investigated the influence of small- and large-dose capsaicin in modulating systemic inflammatory responses during different stages of sepsis in rats. Rats were divided into six groups: group C, control; group S, sepsis; group CLC, small dose of capsaicin (1 mg/kg subcutaneously); group SLC, small dose of capsaicin plus sepsis; group CHC, large dose of capsaicin (150 mg/kg subcutaneously); group SHC, large dose of capsaicin plus sepsis. Rats were made septic by cecal ligation and puncture (CLP). Each group was subdivided into two subgroups. The animals were killed at 9 or 18 h after CLP. Plasma concentrations of calcitonin gene-related peptide (CGRP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and total nitrite/nitrate (NOx) were measured. Superoxide dismutase and malondialdehyde (MDA) were determined in liver, lung, and heart tissues. CGRP was increased in groups S, CLC, and SLC when compared with the other groups. In the SLC group, plasma concentrations of TNF-alpha, IL-6, NOx, and tissue MDA levels were reduced and IL-10 level was increased when compared with groups S and SHC 18 h after CLP (P < 0.05). Small-dose capsaicin treatment increased antiinflammatory IL-10 levels and attenuated the increases in proinflammatory cytokines, NOx, and tissue MDA in septic rats.
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PMID:Small-dose capsaicin reduces systemic inflammatory responses in septic rats. 1550 55

Procalcitonin, a propeptide of calcitonin, is normally produced in the C-cells of the thyroid gland, but it's plasma level markedly increases, mostly due to extra-thyroidal production in cases of severe infections (bacterial, parasitic and fungal) with systemic manifestations, especially in the presence of septic shock. Since noninfectious inflammatory reaction, viral infection and localized bacterial infections manifest only small to modest increases of procalcitonin in plasma, procalcitonin levels may be useful in differentiating between these diseases and sepsis. In addition, it has been suggested that procalcitonin is an early and good marker of elevated cytokines in patients with sepsis, and that it's plasma level is correlated with Sepsis-related Organ Failure Assessment (SOFA) score. Since plasma procalcitonin is measured easily, quickly and accurately by immunoluminometric assay, it is useful for early diagnosis of sepsis in patients with severe systemic inflammatory response syndrome and as an indicator of severity of sepsis in such patients.
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PMID:[Infection and plasma procalcitonin]. 1574 95

Human adipose tissue is a contributor to inflammation- and sepsis-induced elevation of serum procalcitonin (ProCT). Several calcitonin (CT) peptides, including ProCT, CT gene-related peptide (CGRP), and adrenomedullin (ADM) are suspected mediators in human inflammatory diseases. Therefore, we aimed to explore the expression, interactions, and potential roles of adipocyte-derived CT peptide production. Expression of CT peptide-specific transcripts was analyzed by RT-PCR and quantitative real-time PCR in human adipose tissue biopsies and three different inflammation-challenged human adipocyte models. ProCT, CGRP, and ADM secretions were assessed by immunological methods. Adipocyte transcriptional activity, glycerol release, and insulin-mediated glucose transport were studied after exogenous CGRP and ADM exposure. With the exception of amylin, CT peptides were expressed in adipose tissue biopsies from septic patients, inflammation-activated mature explanted adipocytes, and macrophage-activated preadipocyte-derived adipocytes. ProCT and CGRP productions were significantly augmented in IL-1beta and lipopolysaccharide-challenged mesenchymal stem cell-derived adipocytes but not in undifferentiated mesenchymal stem cells. In contrast, ADM expression occurred before and after adipogenic differentiation. Interferon-gamma coadministration inhibited IL-1beta-mediated ProCT and CGRP secretion by 78 and 34%, respectively but augmented IL-1beta-mediated ADM secretion by 50%. Exogenous CGRP and ADM administration induced CT, CGRP I, and CGRP II mRNAs and dose-dependently (10(-10) and 10(-6) m) enhanced glycerol release. In contrast, no CGRP- and ADM-mediated effects were noted on ADM, TNFalpha, and IL-1beta mRNA abundances. In summary, CGRP and ADM are two differentially regulated novel adipose tissue secretion factors exerting autocrine/paracrine roles. Their lipolytic effect (glycerol release) suggests a metabolic role in adipocytes during inflammation.
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PMID:Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullin expression in human adipose tissue. 1576 Oct 41


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