epiglucan and Intestinal-Perforation

Life-threatening intraabdominal candidiasis (IAC) occurs in 30 to 40% of high-risk surgical intensive care unit (ICU) patients. Although early IAC diagnosis is crucial, blood cultures are negative, and the role of Candida score/colonization indexes is not established.. The aim of this prospective Fungal Infection Network of Switzerland (FUNGINOS) cohort study was to assess accuracy of 1,3-β-d-glucan (BG) antigenemia for diagnosis of IAC.. Four hundred thirty-four consecutive adults with abdominal surgery or acute pancreatitis and ICU stay 72 hours or longer were screened: 89 (20.5%) at high risk for IAC were studied (68 recurrent gastrointestinal tract perforation, 21 acute necrotizing pancreatitis). Diagnostic accuracy of serum BG (Fungitell), Candida score, and colonization indexes was compared.. Fifty-eight of 89 (65%) patients were colonized by Candida; 29 of 89 (33%) presented IAC (27 of 29 with negative blood cultures). Nine hundred twenty-one sera were analyzed (9/patient): median BG was 253 pg/ml (46-9,557) in IAC versus 99 pg/ml (8-440) in colonization (P < 0.01). Sensitivity and specificity of two consecutive BG measurements greater than or equal to 80 pg/ml were 65 and 78%, respectively. In recurrent gastrointestinal tract perforation it was 75 and 77% versus 90 and 38% (Candida score ≥ 3), 79 and 34% (colonization index ≥ 0.5), and 54 and 63% (corrected colonization index ≥ 0.4), respectively. BG positivity anticipated IAC diagnosis (5 d) and antifungal therapy (6 d). Severe sepsis/septic shock and death occurred in 10 of 11 (91%) and 4 of 11 (36%) patients with BG 400 pg/ml or more versus 5 of 18 (28%, P = 0.002) and 1 of 18 (6%, P = 0.05) with BG measurement less than 400 pg/ml. β-Glucan decreased in IAC responding to therapy and increased in nonresponse.. BG antigenemia is superior to Candida score and colonization indexes and anticipates diagnosis of blood culture-negative IAC. This proof-of-concept observation in strictly selected high-risk surgical ICU patients deserves investigation of BG-driven preemptive therapy.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Candidiasis; Cohort Studies; Colony Count, Microbial; Female; Humans; Intensive Care Units; Intestinal Perforation; Intraabdominal Infections; Male; Middle Aged; Pancreatitis, Acute Necrotizing; Prospective Studies; Recurrence; Sensitivity and Specificity; Young Adult

Sepsis is associated with the development of progressive damage in multiple organ systems. The beneficial effect of glucans has been attributed to modulation of immune function and enhances defense against bacterial, viral, fungal, and parasitic infections. The aim of this study was to investigate the putative protective effect of ß-glucan on changes of trace element levels in various tissues after experimental sepsis in rats. Sepsis was induced by cecal ligation and perforation (CLP) in 28 male Wistar albino rats. To evaluate this, rats were divided into four groups as sham operated, ß-glucan treated sham operated, CLP, and ß-glucan treated CLP. Sixteen hours after operation, rats were decapitated and zinc (Zn) and copper (Cu) levels were determined in the liver, kidney, heart, diaphragm, and lung tissues. The results demonstrate that sepsis significantly decreased zinc and copper levels of all tissues. The decrease in tissue zinc and copper levels demonstrates the role of trace elements in sepsis-induced tissue damage. Our results indicated that ß-glucan administration did not return the zinc and copper levels to the control group level, and it seems likely that the given dose of ß-glucan was insufficient to prevent sepsis-induced organ injury.

Topics: Animals; beta-Glucans; Copper; Diaphragm; Heart; Intestinal Perforation; Kidney; Ligation; Liver; Lung; Male; Myocardium; Rats; Rats, Wistar; Sepsis; Trace Elements; Zinc

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.

Topics: Animals; beta-Glucans; Cell Line; Cell Nucleus; Cells, Cultured; Cytosol; DNA-Binding Proteins; Gene Expression Regulation; Glucans; I-kappa B Kinase; I-kappa B Proteins; Intestinal Perforation; Ligands; Lipopolysaccharides; Liver; Lung; Macrophages; Male; Mice; Mice, Inbred ICR; NF-kappa B; NF-KappaB Inhibitor alpha; Phosphorylation; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Sepsis; Shock, Septic