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

Recent advances in the diagnosis and therapy of infections in patients with hematological diseases are reviewed. In general, 40-60% of febrile episodes lack clinical or microbiological evidence of infection and are thus treated empirically. Among the cases of microbiologically documented bacteremia treated in our department, the incidence of Gram-negative bacteria was high (47.1%) and the incidence of Gram-positive bacteremia is increasing. To improve the diagnostic rate of Gram-negative sepsis, the measurement of plasma endotoxin was performed. Of 147 febrile neutropenic episodes, endotoxemia was observed in 58 (39.5%) and the causative microorganisms of these infections were deemed Gram-negative bacteria. The measurement of plasma (1-->3)-beta-D-glucan, a ubiquitous component of fungi, was also performed for making early diagnosis of deep mycosis; the sensitivity of this assay was 90% and the specificity was 100%. The detection of (1-->3)-beta-D-glucan appears to be useful as a screening test of deep mycosis. The effects of the concomitant use of granulocyte-colony stimulating factor (G-CSF) and empiric antibiotic therapy for febrile neutropenia were studied in a randomized fashion. G-CSF did not affect the rate of the response to the empiric antibiotic therapy, although a significant effect of G-CSF on neutrophil recovery was observed. Guidelines for empiric antibiotic and antifungal therapy combined with serological diagnosis are proposed.
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PMID:Infections in patients with hematological diseases: recent advances in serological diagnosis and empiric therapy. 940 Dec 73

Soluble carboxymethyl-b-1,3-glucan (CMG), a possible ligand for scavenger receptors, has macrophage-activating action but lacks the granulomatose inflammatory side effect: it is a promising immunomodulator that may mitigate the severity of sepsis. This motivated us to study in rats the effect of CMG (25 mg/kg), injected into the tail vein at 48 and 24 h prior to the administration of 5 mg/kg Escherichia coli 0127.B8 endotoxin on survival, hemodynamic condition, and, in vitro, on the chemiluminescence of PMNs and macrophages, and on macrophagal tumor necrosis factor (TNF) production. Acetylated low density lipoprotein (AcLDL) clearance in vivo and in vitro binding to macrophages was used to study scavenger receptor function. In the nonpretreated group 9 of 10 rats died during the first 24 h after endotoxin, but all CMG-pretreated rats survived. CMG-pretreatment prevented severe decreases in cardiac output and blood pressure after endotoxin. Chemiluminescence of macrophages and PMNs from CMG-pretreated rats was about two times less (p < .05) than that from nonpretreated ones; the endotoxin induced TNF production by macrophages also decreased. Pretreatment with CMG increased, but coinjection of CMG and AcLDL decreased the AcLDL clearance, while coinjection of endotoxin and AcLDL decreased the survival rate. In vitro AcLDL uptake by macrophages decreased after coinjection with CMG. Our results thus showed that CMG was protective in rat endotoxin shock, which seemed partly connected with enhancement of endotoxin clearance through scavenger receptors and to decreased TNF production.
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PMID:Soluble glucan protects against endotoxin shock in the rat: the role of the scavenger receptor. 952 26

Sepsis stimulates an increase in the number and activity of mononuclear phagocytes in systemic host-defence organs. The present study was conducted to define the ultrastructural and cytochemical characteristics of the mononuclear phagocytes that sequester in the lung microvasculature of septic rats. Fourteen rats were challenged with a single intraperitoneal injection of saline (0.5 ml/100 g), E. coli (2 x 10(7)/100 g) or glucan (4 mg/100 g), and euthanased 2, 4, or 7 d later. The lungs were inflation fixed and processed for transmission electron microscopy. Cellular morphology was used to identify the intravascular mononuclear phagocytes and acid phosphatase (AcPase) expression was monitored as an index of cellular differentiation and activation. Control rats contained a limited number of monocytes in the pulmonary vasculature. In contrast, large numbers of activated mononuclear phagocytes were seen in the microvasculature within 48 h of treatment with either microbial product. The recruited pulmonary intravascular mononuclear phagocytes (PIMP) exhibited AcPase-reactive Golgi complexes, accumulation of secretory vesicles and other features of cell activation consistent with enhanced biosynthetic activity. Subsequent electron microscopy, conducted 4 and 7 d posttreatment, suggested that a progressive decline in the number and activity of PIMPs then occurred. In order to quantify the sepsis-induced accumulation of AcPase-positive PIMP, the experimental challenges were repeated in 11 rats and, 48 h later, tissue samples were evaluated by light microscopy for tartrate-insensitive acid phosphatase. Control rats exhibited 0.148 +/- 0.107 AcPase-positive PIMP/alveoli. E. coli and glucan challenged animals exhibited significant (P < 0.01) increases in AcPase-positive mononuclear phagocytes, with 0.782 +/- 0.073 and 0.636 +/- 0.170 PIMP/alveoli respectively. The results demonstrate that focal sepsis stimulates a significant, but transient, recruitment of activated mononuclear phagocytes into the rat pulmonary microvasculature.
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PMID:Ultrastructural and cytochemical evaluation of sepsis-induced changes in the rat pulmonary intravascular mononuclear phagocytes. 956 57

Two immunomodulating polysaccharides, poly-(1-6)-beta-glucotriosyl-(1-3)-beta-glucopyranose (PGG)-glucan and Bacteroides fragilis polysaccharide A (PS A), were evaluated for the prevention of mortality and abscess formation associated with experimental intraabdominal sepsis. Prophylactic treatment with a combination of these compounds significantly reduced mortality (8% vs. 44% in the saline-treated control group) and the incidence of abscesses (30% vs. 100% in the saline-treated control group) after challenge with rat cecal contents. These compounds were also effective when administered therapeutically after bacterial contamination of the peritoneal cavity. PS A treatment conferred long-term protection against abscess formation and resulted in significantly fewer total aerobes and anaerobes in the peritoneal fluid of animals challenged with cecal contents. These data demonstrate the usefulness of two immunomodulatory polysaccharides in preventing experimental intraabdominal sepsis in the absence of antimicrobial therapy and may represent a new adjunct to antibiotic regimens currently used to prevent clinical cases of this disease.
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PMID:Protection against experimental intraabdominal sepsis by two polysaccharide immunomodulators. 965 41

Recent data suggest that sepsis stimulates macrophage apoptosis (Ao) with subsequent induction of macrophage dysfunction. Nuclear factor-kappaB (NFkappaB) activation has been linked to Ao in either a pro- or antiapoptotic role. Glucans are biological response modifiers which exert antisepsis activity. This investigation examined the effect of (1-3)-beta-D-glucan receptor binding by a high affinity ligand on Ao and NFkappaB activation in U937 cells in the presence or absence of LPS. A high affinity glucan ligand (IC50 = 23 nM) activated NFkappaB, but did not induce Ao or significantly alter LPS induced U937 Ao. These data indicate that: i) modulation of the macrophage (1-3)-beta-D-glucan receptor stimulates NFkappaB; ii) does not induce Ao or significantly diminish LPS induced Ao and iii) activation of the U937 FAS receptor does not alter the relative Ao responses in glucan and LPS treated cells.
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PMID:Ligand binding to the (1 --> 3)-beta-D-glucan receptor stimulates NFkappaB activation, but not apoptosis in U937 cells. 971 25

Leukocytes activated by endotoxin or enterotoxins release proinflammatory cytokines, thereby contributing to the cascade of events leading to septic shock. In the present studies, we analyzed the effects of in vivo administration of a soluble immunomodulator, beta-(1,6)-branched beta-(1,3)-glucan (soluble beta-glucan), on toxin-stimulated cytokine production in monocytes and lymphocytes isolated from treated mice. In vitro stimulation of lymphocytes isolated from soluble beta-glucan-treated mice with lipopolysaccharide (LPS) resulted in enhanced production of interleukin-6 (IL-6) and suppressed production of tumor necrosis factor alpha (TNF-alpha), while stimulation of these cells with staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin 1 (TSST-1) resulted in enhanced production of gamma interferon (IFN-gamma) and suppressed production of IL-2 and TNF-alpha compared to that in cells isolated from untreated mice. In vitro stimulation of monocytes isolated from soluble beta-glucan-treated mice with LPS also resulted in suppressed TNF-alpha production, while stimulation of these cells with SEB or TSST-1 resulted in suppressed IL-6 and TNF-alpha production compared to that in cells isolated from untreated mice. Thus, the overall cytokine pattern of leukocytes from soluble beta-glucan-treated mice reflects suppressed production of proinflammatory cytokines, especially TNF-alpha. Taken together, our results suggest that treatment with soluble beta-glucan can modulate the induction cytokines during sepsis, resulting in an overall decrease in host mortality.
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PMID:Modulation of endotoxin- and enterotoxin-induced cytokine release by in vivo treatment with beta-(1,6)-branched beta-(1,3)-glucan. 986 22

The limulus test is a well-established method for the diagnosis of both Gram-negative sepsis and invasive fungal infection. To diagnose fungal infections, a beta-(1-->3)-D-glucan-specific chromogenic kit (Fungitec G test MK) has been developed and applied clinically. We are concentrating our main efforts on developing a better standard to improve the precision of this method. To this end, we have successfully developed a protocol to obtain a soluble Candida spp. beta-(1-->3)-D-glucan (CSBG) by sodium hypochlorite (NaClO) oxidation and subsequent dimethyl sulfoxide (Me2SO) extraction (yield of 9.6 +/- 4.1%) of acetone-dried whole-cell preparations. The beta-glucan fraction is free from the cell-wall mannan, gives a symmetrical peak by gel filtration, and is soluble in dilute NaOH. The product is composed mainly of beta-(1-->3)- and beta-(1-->6)-D-glucosidic linkages. The specific activity of the beta-glucan is comparable with pachyman when combined with the Fungitec G test as the standard glucan and reacted as low as 10(-11) g/mL.
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PMID:Solubilization of yeast cell-wall beta-(1-->3)-D-glucan by sodium hypochlorite oxidation and dimethyl sulfoxide extraction. 1042 May 95

Blood culture is clearly the most important diagnostic procedure for sepsis. In the majority of cases, however, it yields negative results when bacterial or fungal sepsis is strongly suspected in view of an excellent response to antibacterial or antifungal medication. This is likely because infecting microbes have already been too seriously damaged in the blood stream to grow in culture media. Therefore, various tests have been devised to detect cellular components of pathogens including endotoxin for gram-negative bacteria, (1-->3)-beta-D-glucan for fungi, a non-mannan heat-labile candida antigen, glucronoxylomannan for Cryptococcus neoformans, and galactomannan for Aspergillus. The first two tests are particularly suitable for screening purposes, because, in addition to their high sensitivity and specificity, they cover a wide range of species in each category, though not as widely as blood culture. The candida antigen detectable by Candi-Tec is probably a complex of immune-related proteins, and appears to be a poor indicator in immunocompromised hosts. Glucronoxylomannan has been established as a useful marker of cryptococcosis, whereas galactomannan, though highly specific for aspergillosis, needs a more sensitive detection system to be useful for diagnostic purposes.
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PMID:[Non-culture based laboratory diagnosis of sepsis]. 1043 64

The limulus test is a well-established method for the diagnosis of both gram (-) sepsis and invasive fungal infection. To diagnose deep-seated fungal infections, a (1-->3)-beta-D-glucan-specific chromogenic kit (Fungitec G test MK) has been developed and applied clinically. It is suggested that the limulus reactive substance was released from the fungi to the blood, however, its chemical properties were not precisely examined in detail because of the limited quantity available. In this study, we used chemically defined liquid medium to culture Candida spp. and collected the water soluble fraction, CAWS. The yield of CAWS was circa 100 mg/l, independent of the strain of Candida. CAWS reacted with limulus factor G (Fungitec G test MK) at concentrations as low as 100 ng/ml. Limulus factor G reactivity of CAWS was sensitive to (1-->3)-beta-glucanase, zymolyase and was, at least in part, bound to ConA-agarose. The ConA-bound fraction also reacted with anti-beta-glucan antibody. CAWS is mainly composed of mannan and (1-->6)-beta-glucan, in addition to protein, assessed by 1H-NMR spectroscopy. CAWS also reacted with typing sera of Candida spp., specific for cell wall mannan. Chemical, immunochemical and biochemical analyses of CAWS strongly suggested that the limulus factor G-activating substance was a mannan-beta-glucan complex, present within the architecture of the yeast cell wall.
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PMID:Chemical and immunochemical characterization of limulus factor G-activating substance of Candida spp. 1043 60

Growing evidence supports the role of transcription factor activation in the pathophysiology of inflammatory disorders, sepsis, ARDS, SIRS, and shock. Kinase mediated phosphorylation of IkappaBalpha is a crucial step in the NFkappaB activation pathway. We investigated IKBalpha phosphorylation in murine liver and lung extracts after cecal ligation and puncture (CLP) in the presence and absence of a glucan ligand. ICR mice were subjected to CLP. Unoperated and sham-operated mice served as the controls. Glucan phosphate (50 mg/kg) was administered 1 h before or 15 min after CLP. CLP increased hepatic and pulmonary levels of phospho-IkappaBalpha by 48-192%. Pre- or post-treatment with glucan phosphate decreased (P < 0.05) tissue phospho-IkappaBalpha levels in CLP mice. Phospho-IkappaBalpha in the glucan-CLP group were not significantly different from the unoperated controls. To investigate mechanisms we examined IKKbeta kinase activity, IkappaBalpha phosphorylation and degradation, and NFkappaB activity in a murine macrophage cell line, J774a.1, treated with LPS (1 microg/mL) and/or glucan phosphate (1 microg/mL) for up to 120 min. The glucan ligand blunted LPS-induced IKKbeta kinase activity, phosphorylation and degradation of IkappaBalpha, and NFkappaB nuclear binding activity. The data indicate that one mechanism by which (1-->3)-beta-D-glucan may alter the response to endotoxin or polymicrobial sepsis involves modulation of IKK3 kinase activity with subsequent decreases in IkappaBalpha phosphorylation and NFkappaB activation.
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PMID:Inhibition of LPS-induced NFkappaB activation by a glucan ligand involves down-regulation of IKKbeta kinase activity and altered phosphorylation and degradation of IkappaBalpha. 1084 31


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