Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
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.
 ...
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.
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Lactoferrin and prevention of late-onset sepsis in the pre-term neonates. 2013 18

Lactoferrin (Lf) is a mammalian exclusive protein widely distributed in milk and exocrine secretions exhibiting multifunctional properties. Many of the proven or proposed functions of Lf, apart from its iron binding activity, depend on its capacity to bind to other macromolecules. Lf can bind and sequester lipopolysaccharide (LPS), thus preventing pro-inflammatory pathway activation, sepsis and tissue damage. However, the interplay between Lf and LPS is complex, and may result in different outcomes, including both suppression of the inflammatory response and immune activation. These findings are critically relevant in the development of Lf-based therapeutic interventions in humans. Understanding the molecular basis and functional consequences of Lf-LPS interaction will provide insights for determining its role in health and disease.
 ...
PMID:Immunoregulatory role of lactoferrin-lipopolysaccharide interactions. 2019 8

Because of inadequate sample sizes of randomized controlled trials, few immunologic interventions to treat or prevent neonatal sepsis have been reliably evaluated. International collaboration is essential in achieving timely, adequate samples to assess effects on mortality or disability-free survival reliably. Promising or possible therapeutic interventions in severe or gram-negative sepsis include exchange transfusions, pentoxifylline, and IgM-enriched intravenous immunoglobulin. Promising or possible prophylactic interventions include lactoferrin, with or without a probiotic; selenium; early curtailment of antibiotics after sterile cultures; breast milk; and earlier initiation of colostrum in high risk preterm infants. Prophylactic oral probiotics are safe and effective (P<.00001) in reducing all-cause mortality and necrotizing enterocolitis in preterm infants by over half, but do not reduce sepsis.
 ...
PMID:Adjunctive immunologic interventions in neonatal sepsis. 2056 18

We wanted to investigate if plasma levels of antimicrobial polypeptides (AMPs) are increased in severe sepsis and if they correlate with severity and mortality. Samples were collected from 31 sepsis patients at the intensive care unit. The Sequential Organ Failure Assessment (SOFA) score and 90-day mortality were registered, and inflammatory markers and AMP levels were measured by ELISA. A median SOFA score (13) and cardiovascular SOFA score (3) indicated multiorgan failure with severe circulatory derangement, and elevated cytokine levels indicated inflammatory activation. Levels of bactericidal/permeability-increasing protein, heparin-binding protein, alpha-defensins and lactoferrin but not LL-37 were elevated in sepsis patients compared with controls. Bactericidal/permeability-increasing protein levels correlated with mortality, with lower levels in survivors. Levels of all AMPs, except LL-37, positively correlated with the cardiovascular SOFA score. In conclusion, levels of several AMPs are increased in sepsis and correlate with circulatory derangement. This probably reflects neutrophil activation as part of an innate immune response.
 ...
PMID:Elevated plasma levels of antimicrobial polypeptides in patients with severe sepsis. 2057 Dec 57

The role of endotoxin in the genesis of sepsis has long been recognized and multiple treatments aimed at neutralizing it have been studied. Endotoxin can be bound by antibodies (whose role as a therapeutic agent is unlikely), binding proteins such as BPI or human lactoferrin (effectiveness debated and promising respectively) and phospholipid emulsion (which has not improved outcomes in a recent study). Alternatively, the action of endotoxin could be blocked by lipid A analogs (initial study showed no overall benefit and another large trial is near completion targeting a subpopulation of that study). Finally, endotoxin can be bound by polymyxin B embedded in hemoperfusion cartridges. The later treatment has been used for more than a decade in Japan. Since both pre-clinical rationale and studies support the targeting of endotoxin to ameliorate the pro-inflammatory and pro-coagulation response of severe sepsis, this therapeutic intervention is being pursued.
 ...
PMID:Targeting endotoxin in the treatment of sepsis. 2059 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>