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), a 116 amino acid prohormon of calcitonin, is a novel diagnostic marker of severe bacterial infection. The aim of the study was to evaluate the diagnostic usefulness of serum procalcitonin concentration in severely sick patients admitted to the department of internal diseases. Fifty one patients were included into the study and divided into two groups: group A--36 severely sick patients with different medical problems without signs of bacterial infection; group B--15 patients with severe bacterial infection (sepsis--7 patients, pneumonia--6, pyelonephritis--1, peritonitis--1). Twenty eight healthy controls were also included into the study. Serum PCT concentration measured by immunoluminometric assay was undetectable or low in control group (range 0.0-0.1 ng/ml) and group A (range 0.0-1.8 ng/ml). In group B (range 0.0-183 ng/ml) markedly elevated PCT levels were observed in all patients with sepsis, peritonitis and some patients with pneumonia. We conclude that high serum PCT level support the diagnosis of severe bacterial infection.
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PMID:[Diagnostic usefulness of +procalcitonin in internal medicine]. 1071 Sep 46

The pathogenesis of septic shock is mainly due to unregulated tumour necrosis factor-alpha (TNF-alpha) production. Procalcitonin (PCT) and calcitonin gene-related peptide (CGRP) are alternative transcription products of the calcitonin gene. Since high PCT levels have been described in human sepsis, and since CGRP inhibits TNF synthesis in rats, we examined the role of these peptides in the regulation of the inflammatory response during septic shock. LPS-induced TNF production was assessed using a human whole blood model. In this model, PCT (10(-7) M) and CGRP (10(-6) M) significantly inhibit TNF production by 27 and 24 % respectively. The effect of CGRP was reversed by CGRP 8-37 (10 microM), an antagonist of CGRP receptor. No effect on interleukin (IL)-1, IL-6 and IL-8 was found. This is the first description of an anti-inflammatory role for PCT and CGRP in humans.
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PMID:Procalcitonin and calcitonin gene-related peptide decrease LPS-induced tnf production by human circulating blood cells. 1135 14

Adrenomedullin (ADM) is a potent hypotensive peptide, which is produced during sepsis and ischemia. We demonstrate here that hypoxia induced a time-dependent increase of both ADM mRNA and protein expressions in cultured astrocytes and endothelial cells from rat brain microvessels. Gene reporter analyses showed a 2-fold increase in ADM gene transcription which was suppressed when the ADM promoter was deleted of its hypoxia responsive element. Hypoxia increased 7-fold the stability of pre-formed ADM mRNAs. Rat brain microvessels expressed mRNAs coding for the different putative ADM receptors but they did not respond to exogenous ADM and calcitonin gene-related peptide by the formation of cAMP. In contrast, ADM and calcitonin gene-related peptide increased the formation of cAMP in astrocytes and their actions were potentiated about 2-fold after hypoxia. Messenger RNA species coding for three putative ADM receptors (the L1 orphan receptor, RDC-1, and calcitonin receptor-like receptor) and accessory proteins (receptor-activity modifying proteins) were present in astrocytes. Hypoxia selectively up-regulated expression of RDC-1 receptor mRNAs. The results indicate that ADM and RDC-1 are hypoxia-sensitive genes and that RDC-1 receptors may mediate some actions of ADM in hypoxic astrocytes.
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PMID:Coordinated Up-regulation by hypoxia of adrenomedullin and one of its putative receptors (RDC-1) in cells of the rat blood-brain barrier. 1098 Feb

Procalcitonin (PCT), a protein of 116 amino-acids with molecular weight of 13 kDa, was discovered 25 years ago 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. Since 1993 when its elevated level was found in patients with bacterial infection, PCT became an important protein in the detection and differential diagnostics of inflammatory states. The production of PCT during inflammation is linked with a bacterial endotoxin and with inflammatory cytokines (TNF, IL-6). PCT detectable in the plasma during inflammation is not produced in C-cells of the thyroid. The probable site of PCT production during inflammation are the neuroendocrine cells in the lungs or intestine. There is no evidence of plasma PCT binding to cellular receptors of calcitonin, and the role of PCT in calcium and phosphate metabolism during sepsis is still not clear. Other hypothetical roles of PCT (cytokine network regulation, PCT as an endogenous non-steroid antiinflammatory drug) are being considered.
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PMID:Physiology and genetics of procalcitonin. 1098 72

Earlier observations of increased plasma concentrations of immunoreactive calcitonin (32 amino acids) in sepsis and other non-tumorous conditions may be explained by increased secretion of procalcitonin, the 116-amino acid prohormone. At present, the site(s) of origin of procalcitonin in sepsis, the factors regulating its biosynthesis and release, the route(s) of its elimination from blood as well as its biological function(s) are unknown. The rapid increase in procalcitonin concentration in sepsis--in some patients earlier than that of C-reactive protein--and decrease upon successful chemotherapy makes procalcitonin a potentially important biomarker in monitoring patients with suspected or confirmed sepsis.
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PMID:[Increased procalcitonin level in bacteriogenic metabolic disturbances. A new possibility for diagnosis and treatment monitoring in sepsis]. 1103 57

BACKGROUND: Increased serum levels of procalcitonin (ProCT) and its component peptides have been reported in humans with sepsis. Using a hamster model of bacterial peritonitis, we investigated whether serum ProCT levels are elevated and correlate with mortality and hypocalcemia. RESULTS: Incremental increases in doses of bacteria resulted in proportional increases in 72h mortality rates (0, 20, 70, and 100%) as well as increases in serum total immunoreactive calcitonin (iCT) levels at 12 h (250, 380, 1960, and 4020 pg/ml, respectively, vs control levels of 21 pg/ml). Gel filtration studies revealed that ProCT was the predominant (> 90%) molecular form of serum iCT secreted. In the metabolic experiments, total iCT peaked at 12 h concurrent with the maximal decrease in serum calcium. CONCLUSIONS: In this animal model, hyper-procalcitoninemia was an early systemic marker of sepsis which correlated closely with mortality and had an inverse correlation with serum calcium levels.
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PMID:Elevated calcitonin precursor levels are related to mortality in an animal model of sepsis. 1105 17

Although the hemodynamic response to polymicrobial sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase, the factors responsible for producing the transition from the hyperdynamic to the hypodynamic stage are not fully understood. The failure to recognize or prevent this transition may lead to progressive deteriorations in cell and organ functions and ultimately result in multiple organ failure. Despite the fact that several vasoactive mediators (i.e., nitric oxide, prostacyclin, calcitonin gene-related peptide) have been implicated in producing cardiovascular alterations during sepsis, recent studies have indicated that adrenomedullin (AM), a novel vasodilatory peptide, plays an important role in initiating the hyperdynamic response during the early stage of polymicrobial sepsis. In addition, the reduced vascular responsiveness appears to be responsible for producing the transition from the early, hyperdynamic phase to the late, hypodynamic phase of sepsis. Moreover, modulation of AM vascular responsiveness reduces sepsis-induced mortality. In this review the physiological effects of AM, mechanisms of its action, and regulation of its production under various pathophysiological conditions will be discussed. Furthermore, the role of AM in producing the biphasic hemodynamic responses observed during polymicrobial sepsis and approaches for pharmacologically modulating vascular responsiveness and hemodynamic stability under such conditions will be described.
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PMID:The role of adrenomedullin in producing differential hemodynamic responses during sepsis. 1455 33

Although studies have indicated that calcitonin gene-related peptide (CGRP), a potent vasodilatory peptide, is upregulated after endotoxic shock, it remains controversial whether this peptide increases during sepsis and, if so, whether the gut is a significant source of CGRP under such conditions. To study this, polymicrobial sepsis was induced by cecal ligation and puncture (CLP) followed by fluid resuscitation. Plasma levels of CGRP were measured at 2, 5, and 10 h after CLP (i.e., early, hyperdynamic sepsis) and at 20 h after CLP (late, hypodynamic sepsis). The results indicate that plasma CGRP did not increase at 2--5 h but increased by 177% at 10 h after CLP (P < 0.05). At 20 h after the onset of sepsis, however, the elevated plasma CGRP returned to the sham level. To determine the source of the increased plasma CGRP, the liver, spleen, small intestine, lungs, and heart were harvested, and tissue CGRP was assayed at 10 h after CLP in additional animals. Only the small intestine showed a significant increase in tissue levels of CGRP (by 129%, P < 0.05). Determination of portal vs. systemic levels of CGRP indicates that portal CGRP was 65.7 +/- 22.7% higher than the systemic level at 10 h after CLP, whereas portal CGRP in sham-operated rats was only 4.9 +/- 2.1% higher. Immunohistochemistry examination revealed that CGRP-positive stainings increased in the intestinal tissue but not in the liver at 10 h after the onset of sepsis. The distribution of CGRP stainings was associated with intestinal nerve fibers. These results, taken together, demonstrate that upregulation of CGRP occurs transiently during the progression of sepsis (at the late phase of the hyperdynamic sepsis), and the gut appears to be a major source of such an increase in circulating levels of this peptide.
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PMID:The small intestine plays an important role in upregulating CGRP during sepsis. 1120 65

In patients with inflammatory conditions such as infection, cytokines induce the production of C-reactive protein(CRP) and serum amyloid A protein(SAA) in hepatic cells. It has been reported that upon viral infection, the serum SAA level increases by a greater degree than the serum CRP level. Procalcitonin (PCT), the precursor of calcitonin, is a new type of inflammatory marker that is specifically induced by bacterial infection, sepsis and lethal multiple organ failure, but not by viral infection, autoimmune diseases, tumors or surgical stress. To evaluate the immunoluminometric assay(LUMI test PCT; Brahms Diagnostics, Berlin, Germany) procedure for determining the PCT level and to study the clinical significance of the serum PCT level, we determined the serum levels of PCT, CRP and SAA in patients with various inflammatory diseases and normal subjects. The serum PCT level in the normal subjects was < 0.3 ng/ml. Among the patients with inflammatory disease who had a high CRP level(CRP > 20000 micrograms/dl), the PCT level was elevated only in those patients with severe bacterial infection. These results suggest that determining the PCT level may be useful in the differential diagnosis of severe bacterial infection. The patients who had a low CRP level(CRP < 150 micrograms/dl), had a PCT level within the normal range. The patients with autoimmune disease, viral infection, and fungal infection did not have an elevated PCT level.
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PMID:[Assay for determination of the serum procalcitonin level: biochemical and clinical evaluation]. 1121 85

Procalcitonin (PCT) is a highly sensitive and specific marker of systemic bacterial infection and sepsis. In contrast to its diagnostic significance, the cellular sources of plasma procalcitonin remain to be clarified. Two forms of PCT mRNAs originate from calcitonin/calcitonin gene-related peptide gene (CALC-I gene) along with mRNA for calcitonin gene-related peptide-I (CGRP-I). Reverse transcription polymerase chain reaction with newly designed primers detecting different PCT mRNAs and CGRP-I mRNA was used to identify tissues that might contribute to PCT production. Our study indicates that a variety of human tissues (13 of the 16 analyzed overall) express PCT-I, PCT-II, and/or CGRP-I mRNAs, with the highest levels detected for liver, testis, lung, prostate, kidney, and small intestine. Various tissues differ in the proportions of PCT-I, PCT-II, and CGRP-I mRNA expression levels. Thus we demonstrate the complexity of tissue-specific regulation of CALC-I gene expression and suppose a variety of tissues as a potential source of CALC-I-encoded peptides.
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PMID:Procalcitonin and CGRP-1 mrna expression in various human tissues. 1150 61


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