UMLS:C0036690 - FACTA Search

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

Sepsis-induced microvascular leukocyte/endothelial cell interaction may result in a deterioration of capillary perfusion that finally leads to septic organ dysfunction. The aim of the present study was to characterize a novel, sublethal, two-hit model of chronic systemic sepsis that allows the repeated analysis of microcirculation by intravital microscopy. In Syrian golden hamsters the effect of a single i.v. endotoxin (LPS, 2 mg/kg, E. coli) injection (SH-LPS group, n = 5 animals) vs. a double LPS injection (DH-LPS group, n = 6 animals) was analyzed. After monitoring baseline parameters (t1), measurements were performed at 30 min (t2), 3 h (t3), 8 h (t4), 24 h (t5), 48 h (t6), 56 h (t7) and 72 h (t8) (both groups) after initial LPS exposure. In DH-LPS animals, a second LPS injection (2 mg/kg) was given at t6 (48 h). Intravital fluorescence microscopy was performed in a dorsal skin fold chamber preparation and allowed determination of leukocyte-endothelial cell interaction (leukocyte rolling and sticking), and measurement of functional capillary density (FCD), which served as a measure of capillary perfusion. The first LPS injection comparably altered leukocyte/endothelial cell interaction and capillary perfusion in both groups (t1-t6, P > 0.05, MANOVA). Between t6 and t8 leukocyte adherence decreased in SH-LPS animals, whereas in DH-LPS animals adherence remained constantly elevated (SH-LPS: -53.0 +/- 6.2% between t6 and t8 vs. DH-LPS: -3 +/- 5; P < 0.05). The ongoing inflammatory response in DH-LPS animals was associated with a progressive deterioration of FCD, whereas FCD remained constant in SH-LPS animals (DH-LPS: -71.5 +/- 17% between t6 and t8 vs. SH-LPS: 3.0 +/- 13%; P < 0.05). In parallel, coagulatory parameters were found significantly altered only in DH-LPS animals but not in SH-LPS animals. We conclude that "double hit" LPS exposure is an appropriate model (i) to analyze repeatedly over time microcirculatory disorders under conditions of persistent endotoxemia-induced inflammatory response, and (ii) to prove the effectiveness of novel anti-inflammatory strategies.
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PMID:A chronic model for intravital microscopic study of microcirculatory disorders and leukocyte/endothelial cell interaction during normotensive endotoxemia. 1056 10

Using a new concept of terminology for sepsis syndrome, septic shock and multiorgan dysfunction/failure syndrome (MODS/MOSF) as a framework, we have evaluated 21 cases of severe sepsis of new admitted newborns in Neonatology Department of Pediatric clinic of Clinical center University of Sarajevo during last 2 years. We found that the most common etiologic agents were gram negative organisms (Klebsiella pn. and E. coli) and staphylococci. We did not observed any streptococcus group B sepsis despite of high incidence of these infections in developed countries. In 12 (60%) of 21 patients with severe sepsis MODS was developed, involving at least two organ systems, 3 of them also had the other acute insult (emergency surgery and asphyxia) as a possible trigger for MODS. The incidence of specific organ failure was: CNS (58%), respiratory (50%), cardiovascular (41%), the other systems were less involved. The overall mortality rate of patients with sepsis was 28%, whereas the overall mortality rate of MODS/MOSF was 50%.
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PMID:[Septic conditions: a syndrome of multiorgan dysfunction]. 1075 60

Cytokine mediators and leukocyte-endothelial cell adhesion molecules are critical and interdependent components of the acute inflammatory response in sepsis. We hypothesized that the administration of monoclonal antibodies to intercellular adhesion molecule-1 (CD54) or E- and L-selectin (CD62E/L) would decrease serum levels of the proinflammatory cytokines interleukin-1beta (IL-1), IL-6, and IL-8 and tumor necrosis factor receptor (TNFR-1) in baboons during sepsis. Adult male baboons received infusions of 1 x 10(9) colony forming units (CFU)/kg heat-killed Escherichia coli (E. coli) followed 12 h later by live E. coli (1 x 10(10) CFU/kg). At the time of live bacterial infusion, six septic animals were treated with a monoclonal antibody to CD54 and six with an antibody to CD62E and L (1 mg/kg). Eight untreated septic animals served as controls. Sequentially drawn serum samples were assayed for IL-1, IL-6, IL-8, and TNFR-1 using enzyme-linked immunoassay (ELISA). Data were compared using Mann-Whitney U tests and Chi-square analyses. Median survival was decreased in both treatment groups compared to controls (P < 0.05). Peak IL-1 level was higher than controls in septic animals treated with anti-CD54 but not anti-CD62E/L (P < 0.05, P = NS, respectively). Elevations in IL-6, IL-8, and TNFR-1 were increased and prolonged in both antibody treated groups compared to controls (P < 0.05). These results provide the first in vivo evidence that leukocyte-endothelial adhesion molecules CD54 and CD62E/L regulate cytokine production in sepsis.
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PMID:Proinflammatory cytokines increase in sepsis after anti-adhesion molecule therapy. 1080 17

Early postoperative infections and septic complications are predominant causes of morbidity and mortality in patients following orthotopic liver transplantation (OLTx). Prophylactic granulocyte colony-stimulating factor (G-CSF) administration after OLTx was found to decrease the number of sepsis episodes and sepsis-related mortality. Since polymorphonuclear neutrophils (PMNs) are one of the major determinants of antimicrobial defense, alteration of their functions may influence the development of sepsis in these patients. Therefore, we investigated in vitro whether or not priming with G-CSF affects the neutrophils' respiratory burst (RB) in immunosuppressed liver-transplanted patients. Venous blood was drawn from liver allograft recipients (n=12) between the 5th and 15th day postoperatively. Patients without clinical signs of infection or rejection were included in this study. Leukocytes were obtained as supernatant following sedimentation and incubated with 1000 IE ml-1 G-CSF. The RB was measured by the intracellular oxidation of non-fluorescent dihydrorhodamine to the fluorescent rhodamine by flow cytometry. The results were expressed as a percentage of increasing stimulation compared to the control responses, which are made up of the percentage of cells with RB reaction after stimulation with phorbol ester (PMA), bacteria (E. coli), or the combination of a cytokine (TNF-alpha) and a bacterial peptide (FMLP) in the absence of G-CSF. In vitro priming with G-CSF resulted in significantly increased activity of the RB after PMA (from 71.7% to 85.6%) and TNF-alpha/FMLP (from 58.4% to 72.7%) stimulation. These data demonstrate that G-CSF in vitro augments the RB of PMNs, thereby suggesting a possible therapeutic role for G-CSF as immunomodulating agent during bacterial and fungal infections following OLTx.
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PMID:Neutrophil respiratory burst following liver transplantation: in vitro effects of granulocyte colony-stimulating factor. 1142 85

We investigated whether decreases in circulating polymorphonuclear neutrophils (PMN) during lethal Escherichia coli (E. coli) sepsis in canines are related to insufficient host granulocyte colony-stimulating factor (G-CSF). Two-year-old purpose-bred beagles had intraperitoneal E. coli-infected or -noninfected fibrin clots surgically placed. By 10 to 12 h following clot, both infected survivors and nonsurvivors had marked increases (P = 0.001) in serum G-CSF levels (mean peak G-CSF ng/ml +/- SE, 1,931 +/- 364 and 2,779 +/- 681, respectively) compared with noninfected controls (134 +/- 79), which decreased at 24 to 48 h. Despite increases in G-CSF, infected clot placement caused delayed (P = 0.06) increases in PMN (mean +/- SE change from baseline in cells x 10(3)/mm(3) at 24 and 48 h) in survivors (+3.9 +/- 3.9 and +13.8 +/- 3.6) compared with noninfected controls (+13.1 +/- 2.8 and +9.1 +/- 2.5). Furthermore, infected nonsurvivors had decreases in PMN (-1.4 +/- 1.0 and -1.1 +/- 2.3, P = 0.006 compared with the other groups). We next investigated whether administration of G-CSF immediately after clot placement and continued for 96 h to produce more rapid and prolonged high levels of G-CSF after infection would alter PMN levels. Although G-CSF caused large increases in PMN compared with control protein from 2 to 48 h following clot in noninfected controls, it caused much smaller increases in infected survivors and decreases in infected nonsurvivors (P = 0.03 for the ordered effect of G-CSF comparing the three groups). Thus insufficient host G-CSF is unlikely the cause of decreased circulating PMN in this canine model of sepsis. Other factors associated with sepsis either alone or in combination with G-CSF itself may reduce increases or cause decreases in circulating PMN.
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PMID:Acute G-CSF therapy is not protective during lethal E. coli sepsis. 1155 26

We previously reported that a cytostatic protein that is found in ASC-17D Sertoli cell-conditioned media was Mycoplasma arginine deiminase (ADI), which hydrolyzes L-arginine into L-citrulline and ammonia. Here, we report the over-expression of recombinant ADI (rADI) in E. coli and the down-regulation of lipopolysaccharide (LPS) induced-nitric oxide (NO) production by rADI treatment. We cloned the ADI gene from Mycoplasma arginini genomic DNA by a polymerase chain reaction, and changed five TGA tryptophan codons (stop codon in E. coli) to TGG codons in the coding region by site-directed mutagenesis in order to express in E. coli. The rADI was purified to apparent homogeneity by DEAE-Sepharose and arginine-affinity chromatography. The rADI expressed in E. coli was identified as 45 kDa on SDS-PAGE and 90 kDa on native PAGE, implying that it exists as a dimer like ADI of M. arginini. The Km for arginine of rADI was approximately 370+/-50 microM. Its optimal temperature and pH were 41 degrees C and pH 6.4, respectively, and enzyme activity remained > or = 50% for 5 d at physiological temperature and pH. Treatment of purified rADI suppressed NO production in macrophage-like RAW 264.7 and primary glial cells that were exposed to LPS. Furthermore, an intraperitoneal injection of rADI significantly suppressed the rise of blood nitrite/nitrate levels that were induced by the systemic administration of bacterial endotoxin LPS to mice, resulting in an improvement in their survival rate. These results suggest that the depletion of blood arginine with an arginine-metabolizing enzyme, such as ADI, could suppress excessive production of NO that is caused by inducible NOS (iNOS) during the endotoxemia. Also, rADI may be used as a new approach to control NO-related diseases, such as sepsis.
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PMID:Characterization of mycoplasma arginine deiminase expressed in E. coli and its inhibitory regulation of nitric oxide synthesis. 1191 65

A recent clinical sepsis trial reported a significant reduction in 90-day mortality by antithrombin (AT) exclusively in the subgroup of patients without simultaneous heparin prophylaxis. Patients additionally receiving heparin did not benefit from AT treatment. Herein, we studied the microhemodynamic and cellular mechanisms of this adverse effect of heparin on AT actions by the use of intravital microscopy and granulocyte culturing. In Syrian golden hamsters normotensive endotoxemia was induced by 2 mg/kg endotoxin (LPS, E. coli) i.v. In a first group of animals, AT (AT, 250 IU/kg i.v., n = 6) was given 5 min before LPS administration. A second group of animals (Heparin + AT, n = 5) received AT (250 IU/kg i.v.) combined with unfractionated heparin (sodium heparin, 100 IU/kg/24 h, i.v.). Additional animals (LMWH + AT, n = 5) received AT (250 IU/kg i.v.) combined with LMWH (nadroparin 47.5 IU anti-Xa/kg, s.c., 2 h before LPS). LPS-treated animals, which received only saline, served as controls (control, n = 6). Using dorsal skinfold fold preparations, LPS-induced microvascular leukocyte-endothelial cell interaction (LE) and alteration of functional capillary density (FCD) were studied by intravital video fluorescence microscopy. In controls, LPS induced a massive increase in LE with a maximum at 8 h and an impressive decrease in FCD over a 24-hour period. Both LPS effects were effectively prevented by AT treatment (p < 0.01), whereas Heparin + AT and LMWH + AT animals showed microcirculatory alterations comparable to that in controls. In additional in vitro chemotaxis assays. AT blocked neutrophil chemotaxis, an effect reversed by both unfractionated heparin and LMWH. Thus, our study elucidates a relevant in vivo and in vitro unfractionated heparin and LMWH adverse effect in the microcirculatory actions of AT during endotoxemia. These results indicate that heparin should be avoided to permit AT to modulate LPS-induced inflammatory responses.
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PMID:Adverse effect of heparin on antithrombin action during endotoxemia: microhemodynamic and cellular mechanisms. 1219 96

An acute septic inflammatory response with access to the portal circulation was created in a rat model using an intra-abdominal abscess composed of a sterile agar pellet, or one contaminated with 102 Escherichia coli (E. coli) and 109 Bacteriodes fragilis (B. fragilis). After 3 days postimplantation, a well-formed intra-abdominal abscess occurred whose wall showed IL-6 DNA by PCR and IL-6 mRNA by in situ hybridization. Portal venous blood draining into the liver from the intra-abdominal abscess had increased levels of TNF-alpha, IL-1beta, and IL-6 in both sterile and septic groups compared with a control normal animal group. Increased levels of these cytokines were also found in suprahepatic inferior vena caval blood, but were correlated with the higher portal vein levels, suggesting a gradient from abscess wall to portal vein into the systemic circulation via the liver. Liver histology demonstrated sinusoidal congestion centering on the central vein, growing worse with progression from normal in control, to sterile, to septic. Similarly, the degree of intrahepatic myeloperoxidase-positive inflammatory cell infiltration and hepatocellular lipid deposition and apoptosis also increased from control, to sterile, to septic. Gene expression by in situ hybridization demonstrated a significant increase in IL-6 and fibrinogen mRNAs in cells surrounding the central vein in sterile and septic animals, being greatest in animals with sepsis, associated with an increased deposition of collagen in the central vein area, most prominent in the septic liver. The pericentral vein cells with IL-6 and fibrinogen mRNA increases paralleled the increases in cells containing IL-6 and fibrinogen mRNAs in the abscess walls of sterile and septic animals, respectively. The data suggest that an intra-abdominal abscess, especially when contaminated with gram-negative bacteria, induces mRNA-generated cytokine responses in the abscess wall that are related to increased portal venous levels of the inflammatory cytokines TNF-alpha, IL-1beta, and IL-6 perfusing the liver. These, in turn, induce localized production of IL-6 and fibrinogen mRNAs in cells at the central vein area with resultant outflow fibrosis and increased inflammatory cell sequestration within the liver lobular sinuses. This is associated with a generalized inflammatory response and intrahepatic portal sinusoid congestion. There is also increased hepatocellular lipid deposition and apoptosis. Thus, the cytokine production of the abscess wall itself appears to be a major mediator of the septic hepatic response.
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PMID:The septic abscess wall: a cytokine-generating organ associated with portal venous cytokinemia, hepatic outflow fibrosis, sinusoidal congestion, inflammatory cell sequestration, hepatocellular lipid deposition, and focal cell death. 1281 73

A 42-year-old male with a history of chronic aortic valve disease and urethra stenosis, was admitted with fever, dysuria, and vomiting. Escherichia coli (E. coli) was cultured from blood and urine. Repeated transesophageal echocardiographic studies performed during the early phase of the hospitalization did not exclude the possibility of infective endocarditis. A definite diagnosis was, however, not established until 6 weeks after admission. At that time a large paravalvular aortic abscess cavity had developed and urgent surgery was necessary. A possible explanation for the delayed diagnostic evaluation was the low level of suspicion, as the septicemia was believed to originate from the urinary tract, without involvement of other organs. The possibility of endocarditis due to E. coli should be considered, especially in subjects with underlying cardiac valve disease, despite an alternative source of septicemia and despite the rarity of this condition. Frequent echocardiographic studies are recommended since extensive tissue destruction may occur without any striking symptoms.
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PMID:Escherichia coli endocarditis of the aortic valve with formation of a paravalvular abscess cavity. 1569 78

We report a case of sepsis caused by Escherichia coli (E. coli) of serotype O-143. A 78-year-old man developed symptoms of gastroenteritis after ingesting raw meat on noodles. He rapidly developed respiratory failure. Blood culture grew E. coli. The sepsis seemed to have directly spread from a food-borne infection. The development of primary sepsis after ingesting E. coli is very rare. We suspect that bacterial translocation played a major role. Serotype O-143 is recognized in enteroinvasive E. coli (EIEC) as well as in Shigella dysenteriae. The pathogen in the present case is suspected of being EIEC although the isolated E. coli strain was negative for the inv and ipa genes.
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PMID:Sepsis caused by food-borne infection with Escherichia coli. 1641 57

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