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)

1. The effects of parenteral nutrition with or without glutamine supplementation and epidermal growth factor treatment (0.15 microgram/g body weight) was studied in the small bowel of septic rats after 4 days. 2. Septic rats infused with glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment survived sepsis significantly better than other septic rats given parenteral nutrition. The cumulative percentage of deaths over 4 days in septic rats infused with glutamine-supplemented parenteral nutrition was 20% (without epidermal growth factor) and 15% (with epidermal growth factor) compared with 50% in septic rats treated with parenteral nutrition without glutamine and 35% in septic rats given parenteral nutrition without glutamine but with epidermal growth factor treatment. 3. Glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment resulted in improved nitrogen balance in septic rats. The cumulative nitrogen balance over the 4 day period was the least negative as compared with other groups of septic rats. 4. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited marked increases in intestinal net rates of utilization of glutamine (P less than 0.001) and production of ammonia (P less than 0.001) compared with septic rats given parenteral nutrition without glutamine and/or epidermal growth factor treatment. 5. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited significant increases in jejunal wet weight (by 32.4-40.6%), DNA content (by 24.2-34.7%), protein content (by 29.1-50.0%), villus height (by 16.3-26.4%) and crypt depth (by 20.3-29.6%) compared with other groups of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of epidermal growth factor and glutamine-supplemented parenteral nutrition on the small bowel of septic rats. 131 68

The literature does not contain reports regarding teicoplanin overdose in newborns. In a neonate with a history of recent postasphyctic acute renal failure which recovered within 7 days of life, antibiotic therapy with teicoplanin was started for sepsis due to Staphylococcus hominis. However, for 5 days the dosage was excessive (20 mg/kg twice daily instead of an initial dose of 16 mg/kg and then doses of 8 mg/kg once daily). Once this error had been noted, therapy was immediately suspended. Clinically the newborn had improved and blood culture at the end of the therapy was negative. Biohumoral tests revealed constantly normal levels of serum creatinine, serum cystatin C and blood nitrogen. Urinary parameters of tubulotoxicity were also within normal values. Urinary epidermal growth factor was increased. Teicoplanin was well tolerated at the renal level in the newborn even in this case of excessive dosage.
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PMID:Renal tolerability of teicoplanin in a case of neonatal overdose. 982 56

In sepsis, several cell types (e.g., lymphocytes) undergo apoptosis and have the potential to harm the host if not cleared by professional phagocytes. Apoptotic cells display "eat me" signals such as phosphatidylserine that can be readily recognized by phagocytes. For full engulfment of these cells, binding to integrin alpha(v)beta(3), mediated by the bridging protein, milk fat globule epidermal growth factor-factor VIII (MFG-E8), is necessary. We hypothesized that, in sepsis, phagocytosis of apoptotic cells is impaired due to decreased MFG-E8 expression and that adoptive transfer of exosomes containing MFG-E8 is beneficial. Sepsis was induced in rats by cecal ligation and puncture (CLP) and MFG-E8 expression assessed by Western blot 20 h later. Dendritic cells were generated from bone marrow cells, and secreted exosomes were collected and injected into CLP animals. Plasma cytokines (enzyme-linked immunosorbent assay) and thymocyte apoptosis (TC-Ao, annexin V) were assessed. The ability of peritoneal macrophages from septic animals to engulf apoptotic cells was determined in an ex vivo phagocytosis assay. A 10-day survival study was conducted. Cecal ligation and puncture reduced MFG-E8 protein levels in the spleen and liver by 48% and 70%, respectively, and increased TC-Ao by 1.6-fold. Injection of MFG-E8-containing exosomes, however, led to a 33% reduced detection of TC-Ao, without directly inhibiting apoptosis. In fact, peritoneal macrophages from exosome-treated rats displayed a 2.8-fold increased ability to phagocytose apoptotic thymocytes. Inhibition of MFG-E8 before injection of exosomes completely abrogated the enhanced phagocytosis. Treatment with bone marrow dendritic cell-derived exosomes also reduced plasma tumor necrosis factor alpha and interleukin (IL)-6 levels and improved survival from 44% to 81%. We conclude that, by providing the indispensable factor MFG-E8 for complete engulfment of apoptotic cells, these exosomes lead to an attenuation of the systemic inflammatory response and overall beneficial effect in sepsis.
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PMID:Dendritic cell-derived exosomes containing milk fat globule epidermal growth factor-factor VIII attenuate proinflammatory responses in sepsis. 1672 Dec 66

Clearance of apoptotic cells is crucial to maintain cellular function under normal and pathological conditions. We have recently shown that administration of immature dendritic cell-derived exosomes to septic animals promotes phagocytosis of apoptotic cells and improves survival by providing milk fat globule epidermal growth factor-factor VIII (MFG-E8). MFG-E8 acts as an opsonin for apoptotic cells to be engulfed by phagocytosis. In the present study we investigated whether the CX(3)C-chemokine fractalkine (CX(3)CL1) promotes apoptotic cell clearance through the induction of MFG-E8 in peritoneal macrophages. Cultured rat peritoneal macrophages (pMphi) and RAW264.7 macrophages were stimulated with LPS and CX(3)CL1. MFG-E8 expression was assessed by Western blot, cytokine secretion was assessed by ELISA, and phagocytosis of apoptotic thymocytes was determined by microscopy. For in vivo studies, cecal ligation and puncture (CLP) was used to induce sepsis in rats and mice. LPS significantly decreased MFG-E8 levels and phagocytosis of apoptotic cells, whereas CX(3)CL1 induced MFG-E8 expression in both nonstimulated and LPS-stimulated pMphi, without affecting TNF-alpha and IL-6 release. Anti-MFG-E8 blocking antibodies completely abrogated the prophagocytic effect of CX(3)CL1. Twenty hours after the induction of sepsis in rats via CLP, plasma CX(3)CL1 levels as well as MFG-E8 production in peritoneal macrophages decreased by 21% and 56%, respectively. Administration of CX(3)CL1 on the other hand induced MFG-E8 and prevented tissue injury. We conclude that CX(3)CL1 induces MFG-E8 in vitro and in vivo and enhances clearance of apoptotic cells in an MFG-E8-dependent manner. These findings suggest a possible novel treatment for patients in sepsis.
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PMID:Fractalkine-induced MFG-E8 leads to enhanced apoptotic cell clearance by macrophages. 1767 41

To investigate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) in advanced diabetic foot ulcers (DFU) A double-blind trial was carried out to test two rhEGF dose levels in type 1 or 2 diabetes patients with Wagner's grade 3 or 4 ulcers, with high risk of amputation. Subjects were randomised to receive 75 (group I) or 25 mug (group II) rhEGF through intralesional injections, three times per week for 5-8 weeks together with standardised good wound care. Endpoints were granulation tissue formation, complete healing and need of amputation. Safety was assessed by clinical adverse events (AEs) and laboratory evaluations. Forty-one patients were included. After 5-8 weeks of treatment, 83% patients in the higher dose group and 61% in group II achieved useful granulation tissue covering more than 98% of the wound area. At long-term assessment, 13 (56.5%) patients healed in group I and 9 (50%) in group II. The mean time to complete healing in group I was 20.6 weeks (95% CI: 17.0-24.2) and 19.5 weeks (16.3-22.7) in group II. After 1-year follow-up, only one patient relapsed. Amputation was not necessary in 65% and 66.7% of groups I and II, respectively. The AEs rates were similar. The most frequent were sepsis (33%), burning sensation (29%), tremors, chills and local pain (25% each). rhEGF local injection enhances advanced DFU healing and reduces the risk of major amputation. No dose dependency was observed.
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PMID:Intralesional injections of Citoprot-P (recombinant human epidermal growth factor) in advanced diabetic foot ulcers with risk of amputation. 1795 79

Angiopoietin (angpt) 1 and angpt-2 are circulating proteins first ascribed opposing roles in embryonic angiogenesis. Both bind the tyrosine kinase with immunoglobulin-like loop and epidermal growth factor homology domains (Tie) 2 receptor on endothelial cells, but angpt-1 is a Tie-2 agonist, whereas angpt-2 antagonizes Tie-2 signaling. In the developed vasculature, angpt-1 protects against vascular leak, whereas angpt-2 promotes increased vascular permeability. Because alterations in vascular permeability are common in septic shock, we obtained plasma from critically ill children within 24 h of diagnosis of the systemic inflammatory response syndrome (SIRS, n = 20), sepsis (n = 20), or septic shock (n = 61), as well as 15 healthy controls. Plasma levels of angpt-1 and angpt-2 were measured via a commercially available enzyme-linked immunosorbent assay. Plasma angpt-2 levels were significantly elevated in children with septic shock when compared with healthy children, as well as critically ill children with either SIRS or sepsis, and circulating angpt-2 levels seemed to correlate with disease severity and outcome. In addition, plasma angpt-1 levels were significantly decreased in critically ill children with septic shock compared with critically ill children with either SIRS or sepsis. Given the contrasting effects of angpt-2 and angpt-1 on the vascular endothelium, these two factors may play an important role in the pathophysiology of septic shock in children, and further studies are warranted.
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PMID:Admission angiopoietin levels in children with septic shock. 1809 80

Phagocytosis prevents the release of potentially harmful or immunogenic materials from dying cells. Milk fat globule epidermal growth factor (EGF)-factor VIII (MFG-E8) mediates the clearance of apoptotic cells. We have previously shown that the administration of MFG-E8-rich exosomes from immature dendritic cells promotes the phagocytosis of apoptotic cells and improves survival in sepsis. Because endotoxin is elevated in polymicrobial sepsis, we hypothesized that down-regulation of MFG-E8 is mediated via the LPS-CD14 pathway, eventually leading to the accruement of apoptotic cells. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in CD14-deficient (CD14(-/-)), TLR4-mutated and wild-type (WT) mice. In addition, endotoxemia was elicited by i.p. injection of LPS. LPS was also neutralized by pretreating CLP-induced WT mice with polymyxin B. Splenic MFG-E8 expression, phagocytic activity, and apoptosis were assessed 5 and 20 h after CLP or 5 h after LPS administration. In septic WT mice, MFG-E8 mRNA and protein levels were suppressed by 49 and 33%, respectively. Endotoxemia reduced MFG-E8 mRNA expression in a dose dependent manner and the down-regulation of MFG-E8 mRNA expression in CLP-induced sepsis was attenuated by polymyxin B. This CLP-induced suppression was not observed in both CD14(-/-) and TLR4-mutated mice. CLP significantly decreased phagocytic activity of peritoneal macrophages in WT (by 30%), but not in CD14(-/-) mice. CLP also induced significant apoptosis in the spleen of WT (by 61%), but less in CD14(-/-) mice. Thus, MFG-E8 production is down-regulated in sepsis by LPS-CD14 dependent fashion, leading to a reduction of phagocytosis of apoptotic cells.
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PMID:Milk fat globule epidermal growth factor-factor VIII is down-regulated in sepsis via the lipopolysaccharide-CD14 pathway. 1910 91

Thrombomodulin (TM) is an endothelial anticoagulant cofactor that promotes thrombin-mediated activation of protein C. Recently, we conducted a multicentre, double-blind, randomized trial to evaluate the efficacy and safety of recombinant human soluble thrombomodulin (rhsTM, also known as ART-123) for the treatment of disseminated intravascular coagulation (DIC), and found that rhsTM therapy is more effective and safer than low-dose heparin therapy. Thus, in 2008, rhsTM (Recomodulin) was approved for the treatment of DIC in Japan. Here we re-evaluate the therapeutic basis of this drug from the view of its anticoagulant, anti-inflammatory, and cytoprotective properties. Structurally, the extracellular portion of TM is composed of three domains: an N-terminal lectin-like domain (TM-D1), followed by an epidermal growth factor (EGF)-like domain (TM-D2), and an O-glycosylation-rich domain (TM-D3). TM-D2 and TM-D3 are important for the protein's anticoagulant cofactor activities, i.e. inhibition of thrombin and activation of protein C. TM-D1 plays an important role in attenuation of inflammatory responses, through inhibition of leukocyte adhesion to endothelial cells, inhibition of complement pathways, neutralization of lipopolysaccharide (LPS), and sequestration and degradation of pro-inflammatory high-mobility group box 1 protein (HMGB1). Thus, TM on the surface of endothelial cells prevents dissemination of pro-coagulant and pro-inflammatory molecules, and by doing so, allows these molecules to act locally at the site of injury. In patients with sepsis and DIC, TM expression is down-regulated, which may result in dissemination of pro-coagulant and pro-inflammatory molecules throughout the systemic circulation. Replacement with rhsTM may offer therapeutic value in such conditions.
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PMID:Thrombomodulin: protectorate God of the vasculature in thrombosis and inflammation. 2178 Dec 52

Introduction. Inflammation is ubiquitous during sepsis and may be influenced by body mass index (BMI). We sought to evaluate if BMI was associated with serum levels of several cytokines measured at intensive care unit admission due to sepsis. Methods. 33 septic patients were included. An array of thirty-two cytokines and chemokines was measured using Milliplex technology. We assessed the association between cytokine levels and BMI by generalized additive model that also included illness severity (measured by SAPS 3 score); one model was built for each cytokine measured. Results. We found that levels of epidermal growth factor, vascular endothelial growth factor, and interleukins 4, 5, and 13 were associated with BMI in a complex, nonlinear way, independently of illness severity. Higher BMI was associated with higher levels of anti-inflammatory interleukins. Conclusion. BMI may influence host response to infection during critical illness. Larger studies should confirm these findings.
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PMID:Influence of Body Mass Index on Inflammatory Profile at Admission in Critically Ill Septic Patients. 2606 74

There is a need for cellular biomarkers to differentiate patients with sepsis from those with the non-infectious systemic inflammatory response syndrome (SIRS). In this double-blind study we determined whether the expression of known (CD11a/b/c, CD62L) and putative adhesion molecules [CD64, CD97 and epidermal growth factor (EGF)-like molecule containing mucin-like hormone receptor (EMR2)] on blood neutrophils could serve as useful biomarkers of infection and of non-infectious SIRS in critically ill patients. We studied 103 patients with SIRS, 83 of whom had sepsis, and 50 healthy normal subjects, using flow cytometry to characterize neutrophils phenotypically in whole blood samples. Patients with SIRS had an increased prevalence of neutrophils expressing CD11c, CD64 and EMR2 in comparison with healthy subjects (P < 0.001), but normal expression of CD11a, CD11b, CD62L and CD97. An increase in the percentage of neutrophils bearing CD11c was associated with sepsis, EMR2 with SIRS and CD64 with sepsis and SIRS. Neutrophils expressing CD11c had the highest sensitivity (81%) and specificity (80%) for the detection of sepsis, and there was an association between the percentage of neutrophils expressing EMR2 and the extent of organ failure (P < 0.05). Contrary to other reports, we did not observe an abnormal expression of CD11b or CD62L on neutrophils from patients with SIRS, and suggest that this discrepancy is due to differences in cell processing protocols. We propose that blood neutrophils expressing CD11c and EMR2 be considered as potential biomarkers for sepsis and SIRS, respectively.
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PMID:Expression of CD11c and EMR2 on neutrophils: potential diagnostic biomarkers for sepsis and systemic inflammation. 2615 37


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