Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighty-four patients with serious infection due to Entamoeba histolytica were evaluated for systemic complications by objective criteria for dysfunction of the organ systems normally assessed in surgical sepsis. Of 71 patients with amebic liver abscess (ALA), 41% had systemic complications and 13% had more than one organ system involved. Patients > or = 40 years of age and those being treated with steroids were at significantly increased risk of developing complications (P < or = .05). The erythrocyte sedimentation rate and the levels of the acute-phase markers C-reactive protein (CRP) and serum amyloid A (SAA) were significantly elevated in patients with ALA over values in those without ALA (P < or = .05). ALA patients with complications had lower CRP and SAA concentrations than those without complications (P < or = .05). Blood and liver aspirates in ALA patients were usually bacteriologically sterile. The pathogenesis of systemic complications and the associated acute-phase response requires further study, and ways of predicting disease severity and intervening therapeutically must be devised.
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PMID:Systemic manifestations of invasive amebiasis. 145 70

The effects of methyl palmitate (MP), a known inhibitor of Kupffer cells, were studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture (CLP). The inhibition of Kupffer cells by pretreatment with MP was shown by the reduced phagocytosis, the production of tumor necrosis factor (TNF) and interleukin-6 (IL-6) after lipopolysaccharide (LPS) challenge. The reduced activation of Kupffer cells resulted in lower levels of inflammatory products after CLP. TNF and IL-6 were significantly reduced in serum 2 h and 24 h respectively after CLP, interleukin-1 beta (IL-1 beta) was reduced in liver 4 h after CLP, nitric oxide (NO) and serum amyloid A (SAA) were significantly reduced 8 and 24 h respectively after CLP. Liver toxicity was significantly reduced in MP-treated mice and survival was significantly prolonged at all intervals, reaching 45% after six to ten days compared with 3% in control mice. These findings suggest that Kupffer cells play an important role in liver damage and survival in sepsis.
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PMID:Effects of methyl palmitate on cytokine release, liver injury and survival in mice with sepsis. 901 Jun 79

The effect of endotoxemia and sepsis on mucosal production of the acute-phase proteins complement component C3 and serum amyloid A (SAA) was studied in mice. In addition, the role of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)(-1)beta, and IL-6 on mucosal C3 and SAA production was examined. Endotoxemia was induced by the subcutaneous injection of 250 microg/mouse of lipopolysaccharide. Control mice were injected with corresponding volumes of sterile saline solution. Sepsis was induced by cecal ligation and puncture, and sham-operated mice served as controls. Endotoxemia resulted in increased mucosal C3 levels in all parts of the gastrointestinal tract examined, from the stomach to the colon, with the most pronounced effects noticed in the proximal gastrointestinal tract. The influence of endotoxemia on mucosal SAA production was more differentiated with increased levels noted in the jejunum and ileum, and no changes seen in gastric and colonic mucosa. Sepsis resulted in similar changes in mucosal C3 and SAA levels as seen in endotoxemic mice, except that SAA levels were increased in colonic mucosa of septic mice. Among the cytokines, IL(-1)beta resulted in the most pronounced changes in mucosal acute-phase proteins. The increase in C3 and SAA levels in the mucosa of the small intestine during endotoxemia was partially blocked by IL(-1) receptor antagonist. The results suggest that endotoxemia is associated with increased mucosal C3 production in different parts of the gastrointestinal tract and increased SAA production in the mucosa of the small intestine. Mucosal acute-phase protein synthesis may, at least in part, be regulated by IL(-1)beta.
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PMID:Mucosal production of complement C3 and serum amyloid A is differentially regulated in different parts of the gastrointestinal tract during endotoxemia in mice. 1045 12

The systemic response to endotoxin is characterized by hypotension and severe reductions in blood pressure, leading to cardiovascular collapse that can accompany septicemia. The renin/angiotensin system would normally be expected to respond to hypotensive challenge; however, inflammation appears to modify this response. This study identifies a strong acute phase response of the kidney that is characterized by enhanced expression of serum amyloid A, haptoglobin and tissue inhibitor for metalloproteinase-1 and a reduced expression of renin. Equivalent regulatory effects were observed for the immortalized As4.1 kidney cell line that models certain features of juxtaglomerular cells. Oncostatin M, a known endotoxin-responsive proinflammatory cytokine, proved to be an effective inhibitor of renin gene expression. Suppression by oncostatin M involves activated STAT5 and requires an inhibitory element in the renin promoter that functions separately from cell type-specific enhancer elements. The renal acute phase reaction, unlike the liver acute phase reaction, is more strongly dependent on locally produced inflammatory factors.
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PMID:Endotoxin-induced renal inflammatory response. Oncostatin M as a major mediator of suppressed renin expression. 1080 9

The host response to infection, the "acute phase response" is a highly conserved series of physiological reactions including marked changes in concentrations of plasma proteins. These proteins have been shown to participate in the immune response to infections. Several recent studies have elevated the role of acute phase proteins (APPs) as predictive markers in infection. APPs such as serum amyloid A and haptoglobin but not C-reactive protein (CRP) have been identified as markers of inflammation in cattle. In humans, lipopolysaccharide (LPS) binding protein (LBP) has certain biological functions in host defence and participates in acute phase reactions. We measured plasma levels of LBP in a group of 20 calves experimentally infected with Gram-negative Mannheimia haemolytica (Pasteurella) in comparison to haptoglobin, the most widely studied APP in cattle. In infected calves, LBP levels rose significantly 6 h after infection, reaching a maximum at 24 h. Haptoglobin concentrations significantly rose after 12 h, and peak responses were measured 48 h after infection. Thus, LBP may prove to be a diagnostic marker in cattle infection and is faster than haptoglobin in detecting sepsis.
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PMID:A novel acute phase marker in cattle: lipopolysaccharide binding protein (LBP). 1152 Oct 82

Despite the considerable advances made in understanding the pathophysiology of systemic inflammation during critical illness, clinical progress has been elusive as it remains a very deadly condition. Cortisol and thyroid hormone levels can be as predictive of outcome as the commonly used severity parameters (i.e. APACHE). Indeed, levels of endocrine humoral substances such as arachidonic acids, nitric oxide, endothelin, calcitonin precursors, leptin and adenosine correlate with the severity and outcome of critical illness. Furthermore, calcitonin precursors represent a potentially new hormokine paradigm, being transcriptionally activated in all cells in response to infection. The cytokines are immune markers that often correlate with severity and outcome, but their release is transient. In contrast, the so-called acute phase proteins, such as C-reactive protein and serum amyloid A, are highly sensitive to inflammatory activity and can be important markers of severity and outcome. Leukocyte esterase, adhesion molecules, platelet activating factor and activated protein C are additional humoral immune markers; the replacement of the latter has been shown to be a promising therapeutic option. Natriuretic peptides are neurocrine humoral markers that have important cardiovascular implications. The level of macrophage migrating inhibitory factor, released by the pituitary, is elevated in sepsis and counteracts glucocorticoid action. Cellular markers to severe stress include the enhanced expression of protective substances in the form of heat shock proteins. High mobility group-1 is a DNA-binding protein and a late mediator of the inflammatory response. Apoptotic markers such as the soluble fas ligand are also elevated in inflammation. In summary, during critical illness, the endocrine, immune and nervous systems elaborate a multitude of humoral markers, the roles of which merit further scrutiny in order to improve therapeutic outcome.
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PMID:Humoral markers of severity and prognosis of critical illness. 1180 May 23

In order to evaluate serum amyloid A as an early diagnostic marker of late-onset sepsis, seventy-nine preterm infants with clinically suspected sepsis and 40 healthy matched controls were assayed for serum amyloid A. In parallel, clinical and biochemical variables that are used to evaluate neonatal sepsis were compared. Forty-two episodes were diagnosed as sepsis. Serum amyloid A levels were elevated in the sepsis group (187.6 +/- 78.3 micrograms/ml), compared with infants who had no sepsis (10.2 +/- 8.3 micrograms/ml) and the control group (6.9 +/- 3.3 micrograms/ml), and were significantly higher in gram-negative compared to gram-positive sepsis (221.8 +/- 84.4 micrograms/ml vs. 48.5 +/- 22.2 micrograms/ml). Analysis of the data suggests serum amyloid A has the highest sensitivity (100%), specificity (93%) and positive predictive value (96%) for sepsis among the clinical and biochemical parameters that were tested. In conclusion, serum amyloid A seems to be a reliable early marker for the diagnosis of late-onset sepsis in preterm infants.
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PMID:Serum amyloid A protein in the early detection of late-onset bacterial sepsis in preterm infants. 1223 22

Sepsis-induced changes in human plasma decrease LPS association with monocytes by regulating dynamic interactions among LPS, monocytes, and plasma lipoproteins. In the physiological environment of undiluted human serum, we have found that: (i) LPS binds transiently to monocytes and is released into plasma lipoproteins; (ii) the release of LPS from monocytes is dependent upon lipoprotein acceptors and is enhanced by soluble CD14 (sCD14); and (iii) both lipoproteins and sCD14 can attenuate cytokine responses in monocytes that have already bound LPS. Whereas LPS binding protein (LBP) also inhibited LPS responses after LPS had bound to monocytes, this did not require extensive release of cell-bound LPS as was observed with sCD14. In the serum of septic patients, both free LPS and monocyte-bound LPS were usually transferred to lipoproteins at an accelerated rate. In spite of a sharp decline in HDL levels, HDL remained the dominant LPS acceptor in many severely septic patients, whereas in some cases LPS binding shifted largely to a non-HDL lipoprotein fraction that co-eluted according to size with very low-density lipoprotein (VLDL). Preliminary data suggest that these lipoproteins have a very low density, and they contain apolipoprotein E and higher than normal proportions of the total lipoprotein cholesterol, phospholipid, apolipoprotein B, and serum amyloid A. The data suggest that the VLDL fraction contains acute phase lipoproteins of significantly altered composition that can replace HDL as the dominant LPS acceptor during sepsis when HDL levels are low.
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PMID:Impact of sepsis-induced changes in plasma on LPS interactions with monocytes and plasma lipoproteins: roles of soluble CD14, LBP, and acute phase lipoproteins. 1280 85

Sepsis and septic shock are important causes of morbidity and lethality in noncoronary intensive care units. Circulating levels of high-density lipoproteins (HDLs) are reduced in sepsis/septic shock, and the magnitude of this reduction is positively correlated with the severity of the illness. The mechanisms underlying this phenomenon are incompletely understood, although increased levels of several acute-phase proteins, including serum amyloid A (SAA) and secretory phospholipase A2 (sPLA2), may contribute to the decrease in plasma HDLs. It has been suggested that HDLs possess anti-inflammatory properties and, hence, may play a crucial role in innate immunity by regulating the inflammatory response as well as being capable of reducing the severity of organ injury in animals and patients with septic shock. These protective effects of HDLs are mediated mainly via (a) lipopolysaccharide (LPS) binding and neutralization, (b) the HDL-associated enzymes, plasma paraoxonase (PON1) and platelet-activating factor acetylhydrolase (PAF-AH), which protect low-density lipoproteins against peroxidative damage, (c) inhibition of the expression of endothelial cell adhesion molecules and release of proinflammatory cytokines, which prevents inflammatory cell infiltration and subsequent multiple organ dysfunction, and (d) stimulation of the expression of endothelial nitric oxide synthase (eNOS). Thus, HDL exerts potent anti-inflammatory effects, some of which are independent of endotoxin binding and might be useful in the treatment of patients with not only sepsis/septic shock but also other conditions associated with an uncontrolled inflammatory response, such as ischemia-reperfusion injury and hemorrhagic shock.
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PMID:High-density lipoproteins in sepsis and septic shock: metabolism, actions, and therapeutic applications. 1477 33

Infections caused by Gram-negative bacteria constitute one of the major causes of septic shock, which results from the inability of the immune system to limit bacterial spread during the ongoing infection. In the last decade, it has been demonstrated that vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two endogenous immunopeptides, which together with three G protein-coupled receptors (VPAC1, VPAC2, and PAC1) exert a significant, therapeutic effect attenuating the deleterious consequences of septic shock by balancing pro- and anti-inflammatory factors. We have recently shown PAC1 receptor involvement in vivo as an anti-inflammatory receptor, at least in part, by attenuating lipopolysaccharide-induced production of proinflammatory interleukin-6. The present study deepens in the protective role of PAC1 receptor in septic shock, elucidating its involvement in the modulation of neutrophil recruitment and in the expression of different molecular sensors such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, fibrinogen, serum amyloid A, and nitric oxide as important, systemic players of the development of septic shock. Our results, using a mice deficient in PAC1 and a PAC1 antagonist, show that VIP and PACAP as well as the PAC1 receptor are involved in neutrophil recruitment in different target organs, in adhesion molecules expression, and in coagulation-related molecule fibrinogen synthesis. Thus, this study provides some important insights with respect to the involvement of PAC1 into the complexities of sepsis and represents an advantage for the design of more specific drugs complementing standard intensive care therapy in severe sepsis, confirming VIP and PACAP as candidates for multitarget therapy of septic shock.
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PMID:Analysis of the role of the PAC1 receptor in neutrophil recruitment, acute-phase response, and nitric oxide production in septic shock. 1566 28


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