UMLS:C0036690 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0036690 (sepsis)
59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial dysfunction due to sepsis is common in patients with multiple organ dysfunction syndrome and is believed to be produced by inflammatory mediators. Some of these mediators may be eliminated by continuous hemofiltration, which is a standard procedure in an ICU for renal replacement therapy. This study was designed to directly compare the effects of ultrafiltrates from patients with sepsis (UFs) with ultrafiltrates from healthy volunteers (UFh) in well-characterized cardiomyocyte culture systems. Isovolemic hemofiltration (filtration rate: 2 L/h, polyamide membrane) was performed during 12 hours in 5 patients with severe sepsis (Elebute Score >20) and simultaneously reduced left ventricular contractility (left ventricular stroke work index [LVSWI] <30 g m/m2) and in 5 healthy volunteers. Inflammatory mediator concentrations (interleukin [IL]-1beta, IL-6, IL-8, tumor necrosis factor [TNF] alpha, C3a, and C5a) were measured in plasma and ultrafiltrate samples taken shortly after the beginning of the hemofiltration procedure. Cell culture experiments were done comparing UFs with UFh by using spontaneously beating or electrically driven neonatal rat cardiomyocyte cultures. UFs contained significantly higher amounts of IL-1, IL-8, and C3a when compared to UFh. Simultaneously, UFs induced a decrease in the contraction frequency of electrically-stimulated cardiomyocytes, whereas UFh had no effect. The cardiotoxic effect could be reversed by the addition of a high concentration (2.4 mM) of Ca++. Hemofiltration did not alter parameters of cardiac performance during 12 hours in patients with sepsis. UFs induced significant cardiotoxic effects in rat cardiomyocytes, whereas UFh showed no cardiotoxicity. Contact of blood with the hemofiltration membrane did not induce activation of cardiotoxic mediators. Significantly higher filtration rates may be required to improve left ventricular contractility in patients with sepsis by hemofiltration.
...
PMID:Hemofiltrate from patients with severe sepsis and depressed left ventricular contractility contains cardiotoxic compounds. 1048 94

Despite important advances in critical care medicine during the last two decades, the mortality rate of sepsis has remained high, probably because the pathogenesis of sepsis is still incompletely understood. Recent studies have shown that sepsis is a bimodal entity. The first phase is characterized by the systemic release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and IL-8, and by activation of the complement and coagulation cascades. In the second phase, anti-inflammatory mediators such as transforming growth factor-beta (TGF-beta), IL-10 and prostaglandin E2 (PGE2) may be released in an effort to counteract ongoing inflammation. Depending whether the pro- or anti-inflammatory response predominates, sepsis results in a systemic inflammatory response syndrome (SIRS), or a compensatory anti-inflammatory response syndrome (CARS). So far, most efforts to intervene in the immunopathogenesis of sepsis have been directed at the pro-inflammatory response. None of these interventions has been shown to improve the prognosis of sepsis, possibly because many patients were already in a state in which anti-inflammatory responses dominated. Recently, it has been shown that decreased expression of HLA-DR on monocytes in patients with sepsis constitutes a marker for CARS. We suggest that HLA-DR expression on monocytes might constitute a useful indicator of the immunological status of the individual patient with sepsis and a guide for treatment. Patients with CARS, as manifested by low HLA-DR expression, might benefit from immunostimulants, while patients with SIRS and normal or high monocyte HLA-DR expression should receive treatment directed to interfere with pro-inflammatory pathways.
...
PMID:The central role of monocytes in the pathogenesis of sepsis: consequences for immunomonitoring and treatment. 1050 72

To obtain predictors of organ failure (OF), we studied markers of systemic inflammation [circulating levels of interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R), soluble E-selectin and C-reactive protein, and neutrophil and monocyte CD11b expression] and routine blood cell counts in 20 patients with systemic inflammatory response syndrome and positive blood culture. Eight patients with shock due to community-acquired infection developed OF, whereas 11 normotensive patients and one patient with shock did not (NOF group). The first blood sample was collected within 48 h after taking the blood culture (T1). OF patients, as compared with NOF patients, had at T1 a lower monocyte count, a lower platelet count, higher levels of CD11b expression on both neutrophils and monocytes, and higher concentrations of IL-6, IL-8 and sIL-2R. C-reactive protein and soluble E-selectin concentrations did not differ between groups. No parameter alone identified all patients that subsequently developed OF. However, a sepsis-related inflammation severity score (SISS), developed on the basis of the presence or absence of shock and on the levels of markers at T1, identified each patient that developed OF. The maximum SISS value was 7. The range of SISS values in OF patients was 2-5, and that in NOF patients was 0-1. In conclusion, high levels of CD11b expression, depressed platelet and monocyte counts, and high concentrations of IL-6, IL-8 and sIL-2R predict OF in patients with community-acquired septic shock, and the combination of these markers may provide the means to identify sepsis patients who will develop OF.
...
PMID:Markers of systemic inflammation predicting organ failure in community-acquired septic shock. 1054 3

Group B streptococci (GBS) are a major cause of severe infection in newborns, pregnant females, and other immunocompromised hosts. Infection often includes septicemia, shock, pneumonia, and respiratory failure. In previous studies, we have reported that GBS induce marked production of tumor necrosis factor alpha (TNF-alpha) by human mononuclear cells. The present study was designed to measure the production of TNF-alpha as well as additional cytokines, including interleukin 1beta (IL-1beta), IL-6, IL-8, IL-12, and gamma interferon (IFN-gamma) but also to determine from what cells and at what time point during incubation with GBS that these cytokines are produced. Mixed mononuclear cells were incubated with heat-killed GBS, media alone, or 1 microg of Escherichia coli lipopolysaccharide (LPS). Brefeldin A was added to each sample prior to staining, which prevented the export of cytokines by the Golgi apparatus. The cells were then stained with the appropriate conjugated antibodies and analyzed by using a flow cytometer. Results indicate that intracellular cytokines appear, in almost all cases, simultaneous to or before secreted proteins are detected. In contrast to the response to LPS, where TNF-alpha, IL-1beta, IL-6, and IL-8 appear almost simultaneously, the human monocyte response to GBS results in the production of TNF-alpha but delayed appearance of IL-1beta, IL-6, and IL-8. The lymphocyte response to GBS was also strikingly different from that to LPS in that both secreted IFN-gamma and IL-12 was detected, while LPS failed to induce production of these critical cytokines. This suggests an important role for TNF-alpha, IFN-gamma, and IL-12 in GBS pathogenesis and/or immunity.
...
PMID:Intracellular and extracellular cytokine production by human mixed mononuclear cells in response to group B streptococci. 1060 4

Accumulation and activation of inflammatory cells in the lung characterize the acute respiratory distress syndrome (ARDS). However, the precise mechanism for lung epithelial and endothelial cell damage remains unknown. Based on evidence that rapid apoptosis caused by CD8(+) cytolytic T cells can induce pathological cell death, we hypothesized that this mechanism may also participate in the acute lung injury, and attempted to evaluate apoptosis-related factors in bronchoalveolar lavage fluid (BALF) from ARDS patients. Quantitative polymerase chain reaction (PCR) analysis revealed that the messenger ribonucleic acids (mRNAs) for several apoptosis molecules, such as perforin, granzyme A, granzyme B, FasL, and Fas were highly upregulated in the acute phase of ARDS following sepsis. In contrast, low or negligible mRNA expression of these molecules was detected in patients with normal lung function, in septic patients without lung injury (septic non-ARDS), and in patients in the late phase of septic ARDS (late ARDS). While the genes of the classic proinflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8, and inducible nitric oxide synthase (iNOS) were upregulated in septic non-ARDS or late ARDS patients, expressions of these genes in the acute phase of septic ARDS were most distinct. The immunofluorescence flow cytometry showed that only the lymphocyte population in BALF from acute phase of septic ARDS patients expressed perforin and granzyme. The level of soluble FasL in the BALF increased only in the acute ARDS patients. These results thus suggested that the dual apoptosis pathway, perforin/granzyme and FasL/Fas system, is likely to be another participant for the pathogenesis of acute lung injury.
...
PMID:Upregulation of two death pathways of perforin/granzyme and FasL/Fas in septic acute respiratory distress syndrome. 1137 24

Reduced cytokine production in ex vivo cultures has been regularly reported in patients suffering from sepsis syndrome. Using whole blood assays, we have now demonstrated that in sepsis patients, normal production of IL-8 was achieved with the higher concentration of lipopolysaccharide (LPS; 1 microg/ml) and with heat-killed streptococci, whereas the IL-8 production induced by lower LPS concentration (0.1 microg/ml) was significantly reduced as compared to healthy controls. In contrast, in patients undergoing cardiac surgery associated with cardio-pulmonary bypass, a group of patients with inflammation in the absence of infectious insult, none of the studied IL-8 productions were affected. Among the various anti-inflammatory cytokines known to regulate IL-8 production which we tested (i.e. IL-4, IL-10, IL-13, TGF-beta), IL-10 was the most active inhibitory cytokine in whole blood assays performed with blood samples from healthy subjects. However, its activity was not influenced by the amounts of LPS used. In addition, IL-10 also inhibited the heat-killed streptococci-induced IL-8 production and was the only cytokine to inhibit the release of IL-8 when TNF was added to LPS. It is worth noting that IL-13 which also inhibited the heat-killed streptococci-induced IL-8 production, failed to do so when the TNF production was analysed. Together, these data suggest that while circulating IL-10 in septic patients may be responsible for the hyporeactivity of circulating leukocytes, its presence is not sufficient to explain the observed dysregulation which occurs in septic patients.
...
PMID:Interleukin 8 production in whole blood assays: Is interleukin 10 responsible for the downregulation observed in sepsis? 1062 43

Bacterial infection is a major cause of neonatal morbidity and mortality. Early diagnosis is essential for a successful treatment and outcome. Cytokine plasma levels are suggested to be sensitive parameters for the diagnosis of neonatal sepsis. The aim of this study was to assess cytokine mRNA expression in cord blood cells as a marker for neonatal infection. In a prospective study, cord blood samples of neonates with septic bacterial infection were analyzed qualitatively and semiquantitatively by reverse transcriptase-polymerase chain reaction (RT-PCR) for mRNA expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8, as well as for IL-8 cord plasma levels. Results were compared to those of non-septic neonates. A method was used requiring only a microvolume (25 microl or less) of cord blood. Cord plasma levels of IL-8 were significantly elevated in septic infants (n = 9) when compared to infants with not confirmed sepsis (n = 22) and healthy infants that served as controls (n = 68) (median 1,686 vs 262.7 vs 33.1 pg/ml, P < 0.001). The presence of IL-6 and TNF-alpha gene expression was observed more frequently in septic than in non-septic patients; sensitivity, however, reached only 56 and 67%, respectively. When using a semiquantitative approach for analyzing IL-8 mRNA levels, a high sensitivity (86%) and specificity (96%) for the detection of sepsis was achieved. A new method for the early diagnosis of neonatal infection is described measuring cytokine mRNA in neonatal cord blood cells. With this molecular approach only a microvolume of blood is required for analysis.
...
PMID:Elevated gene expression of interleukin-8 in cord blood is a sensitive marker for neonatal infection. 1066 36

Curli organelles are expressed by commensal Escherichia coli K12 and by Salmonella typhimurium at temperatures <37 degrees C, which bind serum proteins and activate the contact-phase system in vitro. This study demonstrates, by means of an anti-CsgA (curli major subunit) antibody, that a significant fraction of E. coli isolates (24 of 46) from human blood cultures produce curli at 37 degrees C in vitro. Serum samples from 12 convalescent patients with sepsis, but not serum from healthy controls, contained antibodies against CsgA (n=12). This study further demonstrates that a curli-expressing E. coli strain and a noncurliated mutant secreting soluble CsgA induce significantly (P<.05) higher levels of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-6, and IL-8) in human macrophages differentiated from THP-1 cells. These data, therefore, provide direct evidence that curli are expressed in vivo in human sepsis and suggest a possible role for curli and CsgA in the induction of proinflammatory cytokines during E. coli sepsis.
...
PMID:Expression of and cytokine activation by Escherichia coli curli fibers in human sepsis. 1066 44

Our objectives were to study the value of different proteins in the serum and ascitic fluid and assess their potential in discriminating between malignant and nonmalignant ascites in a model that could be developed to aid clinical diagnosis. In all, 57 different measurements (30 in serum and 27 in ascitic fluid) including erythrocyte sedimentation rate, number of white blood cells, cytokines, interleukin-1a (IL-1a), IL-1b, IL-2, IL-6, IL-8, tumor necrosis factor-alpha, immunoglobulins (IgG, IgA, IgM), complement factors C3 and C4, acute-phase proteins such as alpha1-acid glycoprotein, alpha2-macroglobulin, alpha1-antitrypsin, haptoglobin, C-reactive protein, ferritin, ceruloplasmin and transferin, were performed in 61 patients with ascites (25 with malignant exudates, 13 with nonmalignant exudates, and 23 with transudates). Patients with sepsis were excluded. Correlation tests and one-way ANOVAs were used for comparisons between different groups. Discriminant analyses were used to assess the significance of each parameter in the differentiation process. Correct classification of 100% of cases required the use of all 57 ascitic fluid measurements in the model, which was not considered practical in clinical diagnosis. Discriminant analysis showed that five ascitic fluid measurements-total protein, LDH, TNF-alpha, C4, and haptoglobin-were sufficient for a model to correctly classify 89% of cases. Cross-validation showed that 70% of unknown cases were correctly classified using this model. In conclusion, we have shown that five easily taken protein measurements in the ascitic fluid can differentiate to a large extent between cases with ascites and have proposed a relatively simple statistical model with these parameters that could be developed to be extremely useful in the clinical setting.
...
PMID:Discrimination between malignant and nonmalignant ascites using serum and ascitic fluid proteins in a multivariate analysis model. 1074 24

Activated neutrophils play an important role in the pathogenesis of sepsis, glomerulonephritis, acute renal failure, and other inflammatory processes. The resolution of neutrophil-induced inflammation relies, in large part, on removal of apoptotic neutrophils. Neutrophils are constitutively committed to apoptosis, but inflammatory mediators, such as GM-CSF, slow neutrophil apoptosis by incompletely understood mechanisms. We addressed the hypothesis that GM-CSF delays neutrophil apoptosis by activation of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI 3-kinase) pathways. GM-CSF (20 ng/ml) significantly inhibited neutrophil apoptosis (GM-CSF, 32 vs 65% of cells p < 0. 0001). GM-CSF activated the PI 3-kinase/Akt pathway as determined by phosphorylation of Akt and BAD. GM-CSF-dependent Akt and BAD phosphorylation was blocked by the PI 3-kinase inhibitor LY294002. A role for the PI 3-kinase/Akt pathway in GM-CSF-stimulated delay of apoptosis was indicated by the ability of LY294002 to attenuate apoptosis delay. GM-CSF-dependent inhibition of apoptosis was significantly attenuated by PD98059, an ERK pathway inhibitor. LY294002 and PD98059 did not produce additive inhibition of apoptosis delay. To determine whether PI 3-kinase and ERK are used by other ligands that delay neutrophil apoptosis, we examined the role of these pathways in IL-8-induced apoptosis delay. LY294002 blocked IL-8-dependent Akt phosphorylation. PD98059 and LY294002 significantly attenuated IL-8 delay of apoptosis. These results indicate IL-8 and GM-CSF act, in part, to delay neutrophil apoptosis by stimulating PI 3-kinase and ERK-dependent pathways.
...
PMID:Granulocyte-macrophage colony-stimulating factor delays neutrophil constitutive apoptosis through phosphoinositide 3-kinase and extracellular signal-regulated kinase pathways. 1075 27

<< Previous 1 2 3 4 5 6 7 8 9 10