Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the effect of C1 inhibitor (C1-inh), an inhibitor of the classical pathway of complement and the contact system, on the physiologic and inflammatory response in baboons suffering from lethal Escherichia coli sepsis. Five animals pretreated with 500 U/kg C1-inh (treatment group; n = 5), followed by a 9-h continuous infusion of 200 U/kg C1-inh subsequent to bacterial challenge, were compared with five controls receiving E. coli alone. Of the treatment group, one animal survived and another lived beyond 48 h, whereas all control animals died within 27 h. In four of five treated animals, less severe pathology was observed in various target organs. C1-inh administration did not prevent the hemodynamic or hematologic changes observed upon E. coli infusion. The activation of fibrinolysis and the development of disseminated intravascular coagulation were essentially unaffected by C1-inh. However, C1-inh supplementation significantly reduced decreases in plasma levels of factor XII and prekallikrein and abrogated the systemic appearance of C4b/c, indicating substantial inhibition of activation of the contact system and the classical complement pathway, respectively. Furthermore, treated animals displayed a reduced elaboration of various cytokines including TNF, IL-10, IL-6, and IL-8. Thus, the administration of C1-inh may have a beneficial but modest effect on the clinical course and outcome of severe sepsis in nonhuman primates. We suggest that activated complement and/or contact system proteases may, at least in part, contribute to the attendant manifestations of septic shock through an augmentation of the cytokine response.
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PMID:Effect of C1 inhibitor on inflammatory and physiologic response patterns in primates suffering from lethal septic shock. 955 6

Sepsis is often associated with a downward spiral through a spectrum of systemic inflammatory response syndrome (SIRS) culminating in organ failure and death. Here we present a 3-year-old girl with Hemophilus influenzae septic meningitis who developed SIRS and acute renal failure. In the initial stage, the patient showed uremia, cytopenia, disseminated intravascular coagulation, elevation of tissue enzyme and ferritin values, hemophagocytosis and overproduction of nitric oxide. The serum cytokine profile revealed increased levels of soluble interleukin (IL)-2 receptor, IL-6, IL-10 and tumor necrosis factor alpha. The patient responded positively to early and intensive interventions including antibiotics, repeated exchange transfusions, dexamethasone and high-dose gamma-globulin. The above laboratory abnormalities almost normalized with clinical improvement. We consider that SIRS was probably responsible for the sequence of events resulting in renal failure in this case, and suggest that renal failure should be included among the serious complications of SIRS associated with Hemophilus influenzae septic meningitis.
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PMID:Systemic inflammatory response syndrome and acute renal failure associated with Hemophilus influenzae septic meningitis. 1087 2

Release of toxins in the organism trigger a cascade of biological and chemical events. The process involves a large number of molecules produced under genetic control in a perfectly regulated chronological order. Certain molecules (TNFx, IL-1, Il-2.) have inflammatory proprieties, generally producing systemic Inflammatory Response Syndrome (SIRS). Other less numerous molecules (IL-4, IL-10) have antiinflammatory actions. Finally, soluble receptors and these cytokines contribute to the decrease in the quantity of active cytokines at the receptor level. Dozens of other molecules, many of which remain to be fully understood, are also found in the blood stream. They can, for example, facilitate white cell adhesion (ICAM, VCAM, selectins.). Some of them (G-CSF. CM-CSF. IL-5) stimulate production of granulocytes, monocytes, eosinophils. More recently, certain peptides, like macrophage inhibiting factor (MIF) and procalcitonin (PCT) have been added to the list of molecules involved in bacterial infections. Coagulation factors are also very rapidly released in response to toxinic aggression triggering disseminated intravascular coagulation. Later, acute-hase inflammation proteins, such as C-reactive protein (CRP), haptoglobin, serum amyloid A, etc. are found in largely increased quantities. All these molecules are potential markers of inflammation. Only a few have however been retained for routine assay due to their fragility and their short-half life or due to analytical difficulties. CRP and PCT can however be used to differentiate viral infections from bacterial infections and are thus routinely used in clinical applications. In the second part of this review, we briefly discuss therapeutic perspectives for severe infections and septic shock. There have been many attempts to neutralize different cytokines but results have been disappointing to date. There are however many possibilities currently under study, particularly neutralization of endotoxins, immunomodulation, use of recombinant C and S proteins, etc.
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PMID:[Inflammatory cascade response to toxin release: therapeutic perspectives]. 1142 20

It is increasingly apparent that there is a bidirectional interaction between the maternal immune system and the reproductive system during pregnancy. Pregnancy is associated with a suppression of maternal specific immune responses, which process underlies the protection of fetal tissues expressing paternally inherited alloantigens. However, recent evidence indicates that the suppression of specific, lymphocyte-mediated immune responses during pregnancy is accompanied by activation of the non-specific arm of the maternal immune response. In the present study, we have investigated the effect of pregnancy on the non-specific immune response induced by bacterial lipopolysaccharide (LPS, endotoxin) in mice. Pregnancy enhanced the LPS-induced production of proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-6, and interferon-gamma. On the other hand, LPS-induced levels of the anti-inflammatory cytokine IL-10 were suppressed in pregnant mice. These alterations in cytokine production correlated with an increased susceptibility for endotoxemic mortality in the pregnant mice. Although adrenergic receptors are important regulators of cytokine production in non-pregnant mice, the alpha(2)- and the beta-adrenoceptor-mediated modulation of cytokine production ceases to operate during pregnancy associated with severe endotoxemia. These data may explain how excessive activation of the non-specific immune responses during pregnancy can contribute to the increased severity of some maternal diseases, including septic shock, and can be an important pathophysiological factor in disseminated intravascular coagulation or preeclampsia.
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PMID:Enhanced tumor necrosis factor-alpha-specific and decreased interleukin-10-specific immune responses to LPS during the third trimester of pregnancy in mice. 1169 56

The amount of inflammatory cytokines is a major determinant for the development of sepsis in very-low-birth-weight (VLBW) neonates. We investigated whether variants of tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-4 receptor alpha-chain, IL-6 and IL-10 genes, associated with altered cytokine production, might influence the risk and complications of sepsis in VLBW infants. We determined the presence of these genetic variants in dried blood samples of 33 septic, 35 infected and 35 healthy VLBW neonates by PCR and RFLP methods and analyzed their association with the risk and complications of sepsis. The frequencies of genetic variants did not differ in uninfected and in infected infants with or without sepsis. Moreover, none of the studied complications was associated with carrier state of any of genetic variants. Four of the 5 septic neonates with disseminated intravascular coagulation, however, carried simultaneously the variants of IL-1 beta and IL-10 genes. We concluded that these genetic polymorphisms do not influence the risk and course of sepsis in VLBW neonates.
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PMID:Genetic variants of TNF-[FC12]a, IL-1beta, IL-4 receptor [FC12]a-chain, IL-6 and IL-10 genes are not risk factors for sepsis in low-birth-weight infants. 1274 52

We report the death of an 18-year-old male with partial ornithine transcarbamylase (OTC) deficiency who participated in a pilot (safety) study of gene therapy. The vector used for this trial was based on human adenovirus type 5, deleted in E1 and E4, and contained human OTC cDNA. It was infused into the right hepatic artery at a dose of 6x10(11)particles/kg. Approximately 18 h. following gene transfer the subject was noted to have altered mental status and jaundice--clinical signs not seen in any of the first 17 subjects in this study. Subsequently, his clinical course was marked by systemic inflammatory response syndrome, biochemically detectable disseminated intravascular coagulation, and multiple organ system failure, leading to death 98 h following gene transfer. Post-mortem examination was consistent with the clinical course, and vector DNA sequences were readily detectable in most tissues. The subject had high serum levels of IL-6 and IL-10 but normal TNFalpha immediately after infusion of the vector. This experience points to the limitations of animal studies in predicting human responses, the steep toxicity curve for replication defective adenovirus vectors, substantial subject-to-subject variation in host responses to systemically administered vectors, and the need for further study of the immune response to these vectors.
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PMID:Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. 1456 64

The persistent mortality from community-acquired pneumonia may be explained by genetic predisposition. Specific mutations or polymorphisms in host response genes that are associated with adverse outcomes from infection can be grouped into four categories: antigen recognition, proinflammatory responses, anti-inflammatory responses, and effector mechanisms. Mannose-binding lectin polymorphisms have a more dominant role in pneumonia when compared with other pattern recognition molecules such as the toll-like receptors. The roles of TNF and lymphotoxin alpha polymorphisms remain unclear despite extensive study. IL-10 and IL-1 receptor antagonist polymorphisms have an important role in the anti-inflammatory response. Specific organ dysfunction, such as ARDS or DIC, may be related to polymorphisms in specific effector genes.
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PMID:Genetic susceptibility to pneumonia. 1580 63

Endotoxic shock, one of the most prominent causes of mortality in intensive care units, is characterized by pulmonary hypertension, systemic hypotension, heart failure, widespread endothelial activation/injury, and clotting culminating in disseminated intravascular coagulation and multi-organ system failure. In the last few years, studies in rodents have shown that administration of low concentrations of carbon monoxide (CO) exerts potent therapeutic effects in a variety of diseases/disorders. In this study, we have administered CO (one our pretreatment at 250 ppm) in a clinically relevant, well-characterized model of LPS-induced acute lung injury in pigs. Pretreatment only with inhaled CO significantly ameliorated several of the acute pathological changes induced by endotoxic shock. In terms of lung physiology, CO pretreatment corrected the LPS-induced changes in resistance and compliance and improved the derangement in pulmonary gas exchange. In terms of coagulation and inflammation, CO reduced the development of disseminated intravascular coagulation and completely suppressed serum levels of the proinflammatory IL-1beta in response to LPS, while augmenting the anti-inflammatory cytokine IL-10. Moreover, the effects of CO blunted the deterioration of kidney and liver function, suggesting a beneficial effect in terms of end organ damage associated with endotoxic shock. Lastly, CO pretreatment prevents LPS-induced ICAM expression on lung endothelium and inhibits leukocyte marginalization on lung parenchyma.
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PMID:Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs. 1622 83

We investigated the role played by cytokines in the mortality of patients with Crimean-Congo hemorrhagic fever (CCHF). Serum levels of several cytokines were measured in 3 patients with fatal CCHF and in 27 patients with nonfatal CCHF. Levels of interleukin (IL)-6 (P< or = .001) and tumor necrosis factor (TNF)-alpha (P = .004) were significantly higher in patients with fatal CCHF than in patients with nonfatal CCHF, whereas levels of IL-10 were not significantly different between the 2 groups (P = .937). Disseminated intravascular coagulation (DIC) scores were also higher in the patients with fatal CCHF (P = .023). Levels of IL-6 and TNF-alpha were positively correlated with DIC scores, whereas levels of IL-10 were negatively correlated with DIC scores. In conclusion, these findings demonstrate that proinflammatory cytokines play a major role in the mortality of patients with CCHF.
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PMID:Evaluation of serum levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha in patients with Crimean-Congo hemorrhagic fever. 1651 55

Monocyte and neutrophil activation occur during microvascular disturbance of disseminated intravascular coagulation (DIC). This study investigated the diagnostic and prognostic value of circulating neutrophil elastase (NE) and neutrophil volume distribution width (NDW) as neutrophil activation markers and circulating soluble CD163 (sCD163) and monocyte volume distribution width (MDW) as monocyte activation markers in 168 patients suspected of having DIC. The sCD163 provided significant diagnostic value. The prognostic value of sCD163 was comparable to that of D-dimer, but was dependent on other coagulation markers. In vitro, thrombin significantly induced sCD163 from monocytes upregulated with IL-10 or dexamethasone. NDW was an independent and powerful prognostic marker. MDW and NE did not provide diagnostic and prognostic power. Excessive thrombin during ongoing DIC induces florid secretion of CD163; sCD163 might therefore be a potential diagnostic and prognostic marker for DIC. NDW, a convenient parameter measured by an automated hematology analyzer, may be an independent prognostic parameter for DIC.
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PMID:Neutrophil and monocyte activation markers have prognostic impact in disseminated intravascular coagulation: in vitro effect of thrombin on monocyte CD163 shedding. 2125 22


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