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

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.
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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.
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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.
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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.
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PMID:Targeting endotoxin in the treatment of sepsis. 2059 74

Bacterial translocation from the gastrointestinal tract is an important pathway initiating late-onset sepsis and necrotizing enterocolitis in very low-birth-weight infants. The emerging intestinal microbiota, nascent intestinal epithelia, naive immunity, and suboptimal nutrition (lack of breast milk) have roles in facilitating bacterial translocation. Feeding lactoferrin, probiotics, or prebiotics has presented exciting possibilities to prevent bacterial translocation in preterm infants, and clinical trials will identify the most safe and efficacious prevention and treatment strategies.
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PMID:New concepts of microbial translocation in the neonatal intestine: mechanisms and prevention. 2081 71

Sepsis-related morbidity and mortality is an increasing concern in all neonatal intensive care units, with reported incidences that are dramatically high regardless of the improvements in the quality of neonatal assistance. Antimicrobial resistance is also becoming a global and regional threat to public health. Neonatal sepsis include bloodstream, urine, cerebrospinal, peritoneal infections, and are classified as early-onset (occurring <3 days of life, EOS) and late-onset sepsis (LOS), i.e., infections arising after the perinatal period. Whereas prevention of EOS relies mainly on maternal-perinatal policies, attempts to reduce LOS incidence are a task merely for neonatologists but are hampered by non-specific clinical features, inadequate sensitivity of diagnostic tests, and late recognition. The frequent occurrence of late neurodevelopmental impairment after LOS challenges neonatologists to seek effective preventative strategies rather than more efficacious antibiotics for treatment. In the area of prevention, consistent evidence is accumulating on fluconazole--for prevention of fungal LOS--and, more recently, on bovine lactoferrin for prevention of both bacterial and fungal LOS: this innate immune system glycoprotein plays an important role in "in vivo" host defenses, and has been shown effective in a multicenter RCT recently published on VLBW neonates. Future studies are warranted to better elucidate the extent of the prevention provided by Ictoferrin and to identify the most suitable dosages to be administered.
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PMID:Clinical use of lactoferrin in preterm neonates: an update. 2108 28

Lactoferrin (LF) is a glycoprotein widely distributed in mammalian organisms. It is synthesized by epithelial cells; hence it is present in secretions of mucous membranes. It is also contained in secondary granules of neutrophils and released to the circulation during trauma, infection or inflammation. LF belongs to the transferrin family--proteins binding iron ions with a high affinity. Upon isolation in 1961 LF was initially called a red, iron-binding protein. LF's ability to bind iron is associated with other functions which the protein fulfils in the body. As described in the part I. of the article, LF participates in acquisition of iron from food and its storage in the body, and to a certain degree also in iron transport to cells. In this part of the article the effect of LF in combating microorganisms by chelating iron is described. The iron-chelating property of LF renders iron inaccessible to the pathogens, thus restricting their growth. Iron, due to its participation in many metabolic processes, is an essential element for almost all microorganisms. Iron is not easily accessible for pathogens within the host. Since iron is crucial for normal function of both pathogens and the host, an ability to acquire iron during infection is regarded as an important virulence factor. Higher vertebrates have evolved a complicated protection system of iron storage and LF is an important element of this system. Low iron-saturated LF effectively combats bacteria and fungi, acting in a bacteriostatic and fungistatic way. The degree of iron saturation also influences antiviral activity of LF. Some pathogens (e.g. Helicobacter pylori, Neisseria sp, Haemophilus influenzae) have evolved a system of siderophores or cellular receptors which can acquire iron from LF and transferrin. The so-called lactoferrin theory of hypoferremia in inflammation assumes, in addition, a protective role of the protein in inflammation, sepsis and trauma. LF, by chelation and storage of plasma iron in the liver and spleen, temporarily restricts its accessibility for microorganisms and processes of formation of toxic, reactive oxygen species, which contributes to the amelioration of inflammatory states.
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PMID:[The role of lactoferrin in the iron metabolism. Part II. Antimicrobial and antiinflammatory effect of lactoferrin by chelation of iron]. 2116 95

Sepsis-related morbidity and mortality are major problems in NICU. Preterm neonates display clinical characteristics that make them prone to infections. Due to the high frequency of severe neurodevelopmental sequelae in survivors, the best possible strategy to manage sepsis in NICU is to prevent them. Hygiene, cohorting, stewardship on use of H2-blockers, steroids and broad-spectrum antibiotic are mandatory, as well as proper management of central venous accesses and surgical devices. In addition, clinical research offers the opportunity of adopting pharmacological preventative strategies such as use of palivizumab to prevent RSV infection, use of fluconazole to prevent fungal sepsis, use of probiotics and lactoferrin to enhance the innate immunity, and use of pagibaximab to prevent staphylococcal sepsis.
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PMID:Recent advances in prevention of sepsis in the premature neonates in NICU. 2125 68

Fungal-related morbidity and mortality is a major concern for most neonatal intensive care units (NICUs) worldwide. Incidence rates are increasing and might be higher than reported due to the challenges associated with diagnosing fungal infections. As preterm neonates display clinical characteristics that make them prone to Candida spp infections, and there is a high frequency of severe neurodevelopmental sequelae in those who survive neonatal fungal infections, specific prevention--rather than empiric or pre-emptive treatment--should be the optimal strategy. Besides stewardship of drug use and efforts to minimize invasive cares, pharmacological prevention with use of fluconazole has proved highly effective in decreasing the rates of fungal sepsis in very low birth weight (VLBW) neonates. Alternative options needing further and more conclusive assessments include use of nystatin, bovine lactoferrin or probiotics.
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PMID:Antifungal prophylaxis in neonates. 2125 70

An episode of sepsis occurs in 20 to 40% of all preterm patients, and such figures have been reported constantly increasing in Neonatal Intensive Care Units. Neonatal sepsis include bloodstream, urine, cerebrospinal, peritoneal infections, infections starting from burns and wounds, or from any other usually sterile sites. Many specific risk factors account for the increased risk of sepsis, including employment of broad-spectrum antibiotics selecting resistant microflora, parenteral nutrition, acid inhibitors and steroids, as well as the systematic and long-lasting use of invasive management. In preterm neonates, loss of gut commensals such as bifidobacteria and lactobacilli, due to the difficulties in oral feeding, or a slower acquisition of them, translates into an increased susceptibility to pathogenic gut colonization. Prompt diagnosis, effective treatment, and specific prophylaxis with antibacterial and antifungal drugs are the milestones of management of these life-threatening events. This article discusses the recent advances in prevention and shows how fluconazole for prevention of fungal sepsis, probiotics for prevention of necrotizing enterocolitis, and bovine lactoferrin for prevention of bacterial sepsis may be considered as effective preventive strategies.
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PMID:[Recent advances in prevention of sepsis in the preterm neonate]. 2139 86


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