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)

Newborns, and especially those delivered preterm, are probably more prone to oxidative stress than individuals later in life. Also during pregnancy, increased oxygen demand augments the rate of production of reactive oxygen species (ROS) and women, even with normal pregnancies, experience elevated oxidative stress and lipid peroxidation compared with nonpregnant women. Also, there appears to be an increase in ROS generation in the placenta of pre-eclamptic women. In comparison with healthy adults, newborn infants have lower levels of plasma antioxidants such as vitamin E, beta-carotene, and sulphydryl groups, lower levels of plasma metal binding proteins including ceruloplasmin and transferrin, and reduced activity of erythrocyte superoxide dismutase. This review summarizes conditions of newborns where there is elevated oxidative stress. Included in this group of conditions is asphyxia, respiratory distress syndrome and sepsis and the review also summarizes the literature related to clinical trials of antioxidant therapies and of melatonin, a highly effective antioxidant and free radical scavenger. The authors document there is general agreement that short-term melatonin therapy may be highly effective and that it has a remarkably benign safety profile, even when neonates are treated with pharmacological doses. Significant complications with long-term melatonin therapy in children and adults also have not been reported. None of the animal studies of maternal melatonin treatment or in postnatal life have shown any treatment-related side effects. The authors conclude that treatment with melatonin might result in a wide range of health benefits, improved quality of life and reduced healthcare costs and may help reduce complications in the neonatal period.
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PMID:Oxidative stress of the newborn in the pre- and postnatal period and the clinical utility of melatonin. 1905 96

Channel catfish Ictalurus punctatus were intraperitoneally challenged with the bacterium Edwardsiella ictaluri (the causative agent of enteric septicemia of catfish), and the expression of genes presumed to function in the inducible innate defense was evaluated. End-binding protein 1 (EB1), beta1-integrin, natural-resistance-associated macrophage protein (Nramp), heat shock protein 70 (Hsp70), serum amyloid P (SAP), and transferrin gene expression profiles were determined using quantitative reverse-transcriptase-polymerase chain reaction on liver, anterior kidney, spleen, and gut. Fish were subsampled at 0, 24, 48, 72, and 96 h after bacterial or phosphate-buffered-saline injection. Posterior kidney sampling demonstrated increasing bacterial counts at 24-48 h postinjection (hpi), followed by a plateau to 96 hpi. The transferrin and SAP transcripts were liver specific. The other genes were expressed in all four tissues. In bacterially infected fish, expression of EB1 (anterior kidney, spleen, and liver), Hsp70 (anterior kidney and spleen), and Nramp (spleen and gut) significantly increased by 48 hpi. Transferrin was strongly up-regulated and SAP was downregulated by 72 hpi, indicating positive and negative acute-phase reactants, respectively. The data indicate a substantial response of innate immunity effector cells by 48 hpi, followed by suppression of bacterial growth and induction of the acute-phase response. This suggests that the 48-72-hpi time frame is critical in our model for evaluating the effectiveness of innate defenses.
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PMID:Expression analysis of selected immune-relevant genes in channel catfish during Edwardsiella ictaluri infection. 1948 23

The congenital disorders of glycosylation (CDG) are a recently described group of inherited multisystem disorders characterized by defects predominantly of N- and O-glycosylation of proteins. Cardiomyopathy in CDG has previously been described in several subtypes; it is usually associated with high morbidity and mortality and the majority of cases present in the first 2 years of life. This is the first case with presentation in late childhood and the article reviews current literature. An 11-year-old female with a background of learning difficulties presented in cardiac failure secondary to severe dilated cardiomyopathy. Prior to the diagnosis of CDG, her condition deteriorated; she required mechanical support (Excor Berlin Heart) and was listed for cardiac transplant. Investigations included screening for glycosylation disorders, and isoelectric focusing of transferrin revealed an abnormal type 1 pattern. Analysis of phosphomannomutase and phosphomannose isomerase showed normal enzyme activity, excluding PMM2 (CDG Ia) and MPI (CDG Ib). Lipid-linked oligosaccharide and mutational studies have not yet defined the defect. Despite aggressive therapy there were persistent difficulties achieving adequate anticoagulation and she developed multiple life-threatening thrombotic complications. She was removed from the transplant list and died from overwhelming sepsis 5 weeks following admission. This case emphasizes the need to screen all children with an undiagnosed cardiomyopathy for CDG, regardless of age, and where possible to exclude CDG before the use of cardiac bridging devices. It highlights the many practical and ethical challenges that may be encountered where clinical knowledge and experience are still evolving.
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PMID:Cardiomyopathy in the congenital disorders of glycosylation (CDG): a case of late presentation and literature review. 1975 45

Transferrin is important in iron metabolism and has been reported to be involved in disease defence responses after bacterial infection. In this study, we identified, sequenced, and characterized the transferrin gene from channel catfish, Ictalurus punctatus. The catfish transferrin gene was similar to those of other vertebrate species with 17 exons and 16 introns. Sequence analysis indicated the presence of the two duplicated lobes, each containing two sub-domains separated by a cleft harboring the iron-binding site, suggesting their structural conservation. The channel catfish transferrin cDNA encodes 679 amino acids with 42-56% similarity to known transferrin genes from various species. Southern blot analysis suggested the presence of two copies of the transferrin gene in the catfish genome, perhaps arranged in a tandem fashion. The catfish transferrin gene was mapped to a catfish BAC-based physical map. The catfish transferrin gene was highly expressed in the liver, but expression was low in most other tested tissues. Transferrin expression was significantly up-regulated after infection with Edwardsiella ictaluri, the causative agent of enteric septicemia of catfish. Such induction was also found with co-injection of iron-dextran and E. ictaluri, while transferrin expression was not significantly induced with the injection of iron-dextran alone.
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PMID:Structure and expression of transferrin gene of channel catfish, Ictalurus punctatus. 1983 70

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

Severe meningococcal sepsis is still of high morbidity and mortality. Its management may be improved by an experimental model allowing better understanding of its pathophysiology. We developed an animal model of meningococcal sepsis in transgenic BALB/c mice expressing human transferrin. We studied experimental meningococcal sepsis in congenic transgenic BALB/c mice expressing human transferrin by transcriptional profiling using microarray analysis of blood and brain samples. Genes encoding acute phase proteins, chemokines and cytokines constituted the largest strongly regulated groups. Dynamic bioluminescence imaging further showed high blood bacterial loads that were further enhanced after a primary viral infection by influenza A virus. Moreover, IL-1 receptor-associated kinase-3 (IRAK-3) was induced in infected mice. IRAK-3 is a negative regulator of Toll-dependant signaling and its induction may impair innate immunity and hence result in an immunocompromised state allowing bacterial survival and systemic spread during sepsis. This new approach should enable detailed analysis of the pathophysiology of meningococcal sepsis and its relationships with flu infection.
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PMID:Experimental meningococcal sepsis in congenic transgenic mice expressing human transferrin. 2181 75

Bacterial cell wall components, such LPS and LTA, are potent initiators of an inflammatory response that can lead to septic shock. The advances in the past were centered around membrane-bound receptors and intracellular events, but our understanding of the initial interactions of these bacterial components with serum proteins as they enter the bloodstream remain unclear. In this study we identified several serum proteins, which are involved in the innate recognition of bacterial products. Using affinity chromatography and mass spectrometry we performed proteomic analysis of LPS- and LTA-binding serum proteins. We isolated proteins from normal serum that can interact with LPS and LTA. Fluorescent binding experiments and cytokine assays revealed that serum proteins, such as apolipoprotein, LDL, transferrin and holotransferrin could neutralize LPS/LTA binding as well as the subsequent inflammatory response, suggesting that serum proteins modulate LPS/LTA-induced responses. When compared with the proteomic profile of serum from septic patients it was shown that these proteins were in lower abundance. Investigation of serum proteins in 25 critically ill patients with a mortality rate of 40% showed statistically higher levels of these proteins in survivors. Patients surviving sepsis had statistically significant higher levels of apolipoprotein, albumin, LDL, transferrin and holotransferrin than individuals that succumbed, suggesting that these proteins have an inhibitory effect on LPS/LTA-induced inflammatory responses and in their absence there might be an augmented inflammatory response in sepsis.
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PMID:Serum proteins modulate lipopolysaccharide and lipoteichoic acid-induced activation and contribute to the clinical outcome of sepsis. 2246 Jun 33

Neisseria are pathogenic bacteria that cause gonorrhea, septicemia, and meningitis. Like other pathogenic bacteria, Neisseria must acquire iron for survival from their local environment within the human host. Instead of secreting siderophores to scavenge iron, Neisseria steal iron from human iron binding proteins such as hemoglobin, transferrin and lactoferrin for survival. Recently we reported the crystal structures of the Neisseria meningitidis transferrin receptors TbpA and TbpB, as well as the structures of apo and holo human transferrin. We also analyzed these proteins using small angle X-ray scattering and electron microscopy to provide the molecular details explaining how Neisseria are able to interact with and extract iron from transferrin. Here, we utilize the structural reports, as well as the recently reported structure of the N-lobe of LbpB from Moraxella bovis, to assemble improved 3D homology models for the neisserial lactoferrin import receptors LbpA and LbpB, both of which are important vaccine targets against N. meningitidis. We then analyzed these models to gain structural insights into the lactoferrin-iron import system and form a mechanistic model fashioned in parallel to the homologous transferrin-iron import system.
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PMID:Structural insight into the lactoferrin receptors from pathogenic Neisseria. 2346 98

Lactoferrin (Lf) is an iron-binding glycoprotein of the transferrin family, which is expressed in most biological fluids with particularly high levels in mammalian milk. Its multiple activities lie in its capacity to bind iron and to interact with the molecular and cellular components of hosts and pathogens. Lf can bind and sequester lipopolysaccharides, thus preventing pro-inflammatory pathway activation, sepsis and tissue damages. Lf is also considered a cell-secreted mediator that bridges the innate and adaptive immune responses. In the recent years much has been learned about the mechanisms by which Lf exerts its activities. This review summarizes the recent advances in understanding the mechanisms underlying the multifunctional roles of Lf, and provides a future perspective on its potential prophylactic and therapeutic applications.
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PMID:Immunomodulatory effects of lactoferrin. 2478 30

Capnocytophaga canimorsus, a dog mouth commensal and a member of the Bacteroidetes phylum, causes rare but often fatal septicemia in humans that have been in contact with a dog. Here, we show that C. canimorsus strains isolated from human infections grow readily in heat-inactivated human serum and that this property depends on a typical polysaccharide utilization locus (PUL), namely, PUL3 in strain Cc5. PUL are a hallmark of Bacteroidetes, and they encode various products, including surface protein complexes that capture and process polysaccharides or glycoproteins. The archetype system is the Bacteroides thetaiotaomicron Sus system, devoted to starch utilization. Unexpectedly, PUL3 conferred the capacity to acquire iron from serotransferrin (STF), and this capacity required each of the seven encoded proteins, indicating that a whole Sus-like machinery is acting as an iron capture system (ICS), a new and unexpected function for Sus-like machinery. No siderophore could be detected in the culture supernatant of C. canimorsus, suggesting that the Sus-like machinery captures iron directly from transferrin, but this could not be formally demonstrated. The seven genes of the ICS were found in the genomes of several opportunistic pathogens from the Capnocytophaga and Prevotella genera, in different isolates of the severe poultry pathogen Riemerella anatipestifer, and in strains of Bacteroides fragilis and Odoribacter splanchnicus isolated from human infections. Thus, this study describes a new type of ICS that evolved in Bacteroidetes from a polysaccharide utilization system and most likely represents an important virulence factor in this group.
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PMID:New iron acquisition system in Bacteroidetes. 2536 14


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