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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A basic challenge in the treatment of septic patients in critical care units is the release of bacterial pathogenicity factors such as lipopolysaccharide (LPS, endotoxin) from the cell envelope of Gram-negative bacteria due to killing by antibiotics. LPS aggregates may interact with serum and membrane proteins such as LBP (lipopolysaccharide-binding protein) and CD14 leading to the observed strong reaction of the immune system. Thus, an effective treatment of patients infected by Gram-negative bacteria must comprise beside bacterial killing the neutralization of endotoxins. Here, data are summarized for synthetic compounds indicating the stepwise development to very effective LPS-neutralizing agents. These data include synthetic peptides, based on the endotoxin-binding domains of natural binding proteins such as lactoferrin, Limulus anti-LPS factor, NK-lysin, and cathelicidins or based on LPS sequestering polyamines. Many of these compounds could be shown to act not only in vitro, but also in vivo (e.g. in animal models of sepsis), and might be useful in future clinical trials and in sepsis therapy.
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PMID:Mechanisms of endotoxin neutralization by synthetic cationic compounds. 1705 90

The treatment of children affected by severe congenital neutropenia (SCN) with G-CSF strongly reduces the risk of sepsis by reversing neutropenia. However, SCN patients who respond to the treatment with the growth factor still have an elevated risk of succumbing to sepsis. Because the disease is usually caused by heterozygous mutations of ELA2, a gene encoding for neutrophil elastase (NE), we have investigated in G-CSF-responder and nonresponder patients affected by SCN the expression of polypeptides that constitute the antimicrobial machinery of these cells. In peripheral blood-derived neutrophils of patients with heterozygous mutations of ELA2 who were treated with G-CSF, NE was nearly absent as detected by immunofluorescence and immunoblotting, suggesting that production of the mutant protein interferes with normal gene expression. This defect was associated with abnormal expression of other granule-associated proteins such as myeloperoxidase, lactoferrin, cathepsin G, and human-neutrophil-peptide. Moreover, in one patient with partial response to G-CSF, we observed an impairment of neutrophil antimicrobial activity against Candida albicans, and, to a lower extent against Escherichia coli. Thereby, we propose that the treatment with G-CSF is not sufficient to correct all of the functional deficiency of neutrophils, and this might account for the consistent risk of infections observed in SCN patients.
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PMID:G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms. 1788 43

Possibilities of using C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), lactoferrin (LF) and sorption ability of erythrocytes (SAE) as markers of the severity, prognosis and criteria of effectiveness of treatment were studied in 334 patients with abdominal sepsis. The investigation of the sepsis marker dynamics has shown that fast kinetics of CRP and PCT makes it impossible to assess the prognosis and effectiveness of treatment using these markers. IL-6, LF and SAE are the only ones to be used for this purpose.
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PMID:[Clinical significance of inflammation markers in abdominal sepsis patients]. 1766 73

Neonatal sepsis causes significant mortality and morbidity. Coagulase-negative staphylococci (CoNS) and Candida frequently cause neonatal sepsis at >72 h of age. Lactoferrin, which is present in human milk, is a component of innate immunity and has broad-spectrum antimicrobial activity. The synergistic effects of lactoferrin with antibiotics against neonatal isolates have not been systematically evaluated. Here, eight clinical strains (seven neonatal) of CoNS and three strains (two neonatal) of Candida albicans were studied. MIC50 and MIC90 values of human recombinant lactoferrin (talactoferrin; TLF), vancomycin (VAN) and nafcillin (NAF) against CoNS, and of TLF, amphotericin B (AMB) and fluconazole (FLC) against C. albicans, were evaluated according to established guidelines. Antimicrobial combinations of TLF with NAF or VAN against CoNS, and TLF with AMB or FLC against C. albicans, were evaluated by a checkerboard method with serial twofold dilutions. Synergy was evaluated by the median effects principle, and combination indices and dose reduction indices were reported at 50, 75 and 90% inhibitory effect at several drug-dose ratios. It was found that TLF acted synergistically with NAF and VAN against CoNS, and with AMB and FLC against C. albicans, at multiple dose effects and drug-dose ratios with few exceptions. In synergistic combinations, drug reduction indices indicated a significant reduction in doses of antibiotics, which may be clinically relevant. Thus TLF acts synergistically with anti-staphylococcal and anti-Candida agents commonly used in neonatal practice and is a promising agent that needs to be evaluated in clinical studies.
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PMID:Human recombinant lactoferrin acts synergistically with antimicrobials commonly used in neonatal practice against coagulase-negative staphylococci and Candida albicans causing neonatal sepsis. 1871 81

Plasma lactoferrin dynamics was investigated in 120 of the 2250 patients with local and generalized soft tissue infections. Systemic symptoms were observed in 15% of the patients with soft tissue infections, syndrome of systemic inflammatory response in 13%, and sepsis in 42%. In 89% of the patients with systemic inflammatory reactions the blood lactoferrin level was 1.1-1.3 times the normal one within 72 hours after the onset of therapy; it dropped to the normal value in 12-15 days. Normalization of blood lactoferrin in patients with mild and moderate systemic inflammatory reactions roughly coincided with the disappearance of symptoms of generalized infection. It occurred 5-6 days after the septic process was resolved in patients with severe inflammatory reactions. Normal blood lactoferrin levels were characteristic of a mild inflammatory reaction and local forms of infection. A rise in blood lactoferrin above 1400 ng/ml combined with the syndrome of systemic inflammatory reaction over 72 hr in duration was regarded as a diagnostic criterion of sepsis. It is suggested that monitoring blood lactoferrin during treatment of systemic inflammatory reactions and sepsis be used for the choice of therapeutic strategy and the assessment of efficiency of its efficiency.
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PMID:[The use of plasma lactoferrin in the diagnosis of pyonecrotic infections of soft tissues and sepsis]. 1906 57

Despite the use of potent antimicrobials, neonatal sepsis and necrotizing enterocolitis are associated with significant mortality and morbidity. The emergence of microbial antibiotic resistance is a grave concern. Inflammation secondary to sepsis and necrotizing enterocolitis increases pulmonary and cerebral morbidity. New strategies that target inflammation and reduce the emergence of antibiotic resistance are urgently needed. Lactoferrin has broad-spectrum antimicrobial and immunomodulatory activities. In animal models of colitis, lactoferrin reduces inflammatory injury. Lactoferrin also induces the receptor-mediated proliferation and differentiation of intestinal cells. A randomized, controlled trial of lactoferrin in premature neonates to prevent late-onset sepsis is currently in progress. Lactoferrin is a promising agent in the prevention of neonatal sepsis and necrotizing enterocolitis but needs further evaluation to confirm its safety, tolerability and efficacy.
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PMID:Can lactoferrin prevent neonatal sepsis and necrotizing enterocolitis? 1948 92

Dynamic measurements of blood TNF-a, IL-IRA, CRP, oligopeptide, and lactoferrin levels in patients with systemic and local soft tissue infections revealed direct correlation between them which allowed to use these indicators for the diagnosis of systemic infections. Results of clinical and laboratory analyses provided a basis for distinguishing short-term systemic inflammatory response syndrome and sepsis and developing relevant diagnostic criteria. Sepsis combined with systemic inflammatory response syndrome persisting for more than 72 hours after the onset of adequate therapy was characterized by CRP levels > 30 mg/l, oligopeptides > 0.34 U, lactoferrin > 1900 ng/ml, TNF-a > 6 pg/ml, ILL-IRA < 1500 pg/ml Patients with systemic inflammatory response syndrome for less than 72 hours had lower TNF-a, CRP, oligopeptide, and lactoferrin levels with IL-IRA > 1500 pg/ml. This new approach to early diagnosis of systemic infections makes it possible to optimize their treatment and thereby enhance its efficiency.
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PMID:[A new approach to clinical and laboratory diagnosis of systemic and local soft tissue infections]. 1951 7

Bcr and Abr are GTPase-activating proteins for the small GTPase Rac. Both proteins are expressed in cells of the innate immune system, including neutrophils and macrophages. The function of Bcr has been linked to the negative regulation of neutrophil reactive oxygen species (ROS) production, but the function of Abr in the innate immune system was unknown. Here, we report that mice lacking both proteins are severely affected in two models of experimental endotoxemia, including exposure to Escherichia coli lipopolysaccharide and polymicrobial sepsis, with extensive microvascular leakage, resulting in severe pulmonary edema and hemorrhage. Additionally, in vivo-activated neutrophils of abr and bcr null mutant mice produced excessive tissue-damaging myeloperoxidase (MPO), elastase, and ROS. Moreover, the secretion of the tissue metalloproteinase MMP9 by monocytes and ROS by elicited macrophages was abnormally high. In comparison, ROS production from bone marrow monocytes was not significantly different from that of controls, and the exocytosis of neutrophil secondary and tertiary granule products, including lactoferrin, was normal. These data show that Abr and Bcr normally curb very specific functions of mature tissue innate immune cells, and that each protein has distinct as well as partly overlapping functions in the downregulation of inflammatory processes.
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PMID:Bcr and Abr cooperate in negatively regulating acute inflammatory responses. 1970 97

The investigation of results of treatment included the observation of 2250 patients with pyo-necrotic diseases of soft tissues. For the early diagnosis of sepsis the indices of C-reactive protein, oligopeptides and lactoferrin of blood were used. In the presence of one or more symptoms of the systemic inflammatory reaction the level of the indices was increased from 1.1-3.1 up to 4-7 times depending on the degree of the systemic response severity. When the inflammatory process was local the data of the markers remain normal. These markers allow the confirmation of the clinical diagnosis of sepsis, assessment of the degree of the systemic inflammatory reaction and prognosis of the disease.
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PMID:[Determination of the concentration of C-reactive protein, oligopeptides and lactoferrin of blood as a method of early diagnosis of mesenchymal sepsis]. 1994 16

Late-onset sepsis (LOS) affects a large proportion of pre-term neonates in neonatal intensive care units (NICUs) worldwide, with high morbidity and related mortality, and frequent occurrence of severe late neurodevelopmental impairment. Due to the frequency, severity and difficulties in early diagnosis and prompt therapy, prevention is crucial for decreasing the burden of infection-related complications in NICUs. It is well known that feeding with fresh maternal milk, hygiene measures and the cautious use of H2-blockers are related with a decreased risk of developing sepsis. However, evidence from randomised clinical trials exists only for fluconazole in the prevention of fungal infections in the NICU. Lactoferrin is the main whey protein in mammalian milk, and is involved in innate immune host defences. Notably, human lactoferrin can be found at increased concentrations in colostrum and in milk from mothers of premature neonates. Human (hLF) and bovine lactoferrin (bLF) share a high (77%) amino-acid homology, and the same N-terminal peptide responsible for antimicrobial activity, called lactoferricin. In vitro, bLF shows potent direct antimicrobial activity against all types of pathogens, which occurs via anti-cell wall actions and leads to disintegration of the micro-organism's membranes. bLF is also synergistic with many antimicrobials and antifungals, and promotes growth and differentiation of the immature gut. Based on this background data, a randomised clinical trial was recently conducted in very low birth weight pre-term neonates given bLF alone or with the probiotic Lactobacillus GG. The aim of the trial was to assess the ability of bLF to prevent late-onset sepsis of any origin in the studied infants during their stay in the NICU. This article discusses the preliminary data from this study, along with the proposed mechanisms of action of bLF in pre-term infants.
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PMID:Lactoferrin and prevention of late-onset sepsis in the pre-term neonates. 2013 18


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