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)

Coagulase-negative staphylococci (CNS) have gained substantial interest as pathogens involved in nosocomial, particularly catheter-related infections. The pathogenic potential of CNS is mainly due to their capacity to form biofilms on indwelling medical devices. In a biofilm, the bacteria are protected against antibiotics and from attacks by the immune system. The factors contributing to biofilm formation are among the best-studied virulence factors of CNS and comprise factors involved in the adhesion to a catheter surface and in cell accumulation. CNS usually persist in the host in relative silence, but may cause sepsis, for which the recently found inflammatory peptides called phenol-soluble modulins are prime candidates. Many CNS also produce several lipases, proteases, and other exoenzymes, which possibly contribute to the persistence of CNS in the host and may degrade host tissue. We are also beginning to understand how regulators of virulence trigger the expression of virulence factors in CNS. A better conception of the mechanisms underlying the pathogenicity and the frequently encountered antibiotic resistance of CNS may help to develop novel, efficient anti-staphylococcal therapeutics.
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PMID:Virulence factors of the coagulase-negative staphylococci. 1476 14

Staphylococcus epidermidis releases a group of peptides termed phenol-soluble modulin (PSM) that stimulate macrophages. The structure of 3 peptides (PSM alpha, PSM beta, and PSM gamma ) have been described. We report a fourth peptide (PSM delta ), which is a 23mer with the structure fMSIVSTIIEVVKTIVDIVKKFKK. The gene for each of the 4 peptides was introduced singly into Staphylococcus carnosus, and the PSM-like activity of culture medium and bacterial extract were significantly greater than those of the parent strain. PSM peptides from each of the S. carnosus-expressing strains were purified and analyzed by liquid chromatography-mass spectrometry. The products, which appeared to form aggregates, were active in the activation of human immunodeficiency virus type 1 long-terminal repeat and the production of tumor necrosis factor- alpha by the macrophage cell line THP-1. These findings suggest that PSM peptides are responsible, in part, for the modulin-like activity of staphylococci and may contribute to the development of severe staphylococcal sepsis.
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PMID:Activity of Staphylococcus epidermidis phenol-soluble modulin peptides expressed in Staphylococcus carnosus. 1527 3

A 43-year-old man was admitted with jaundice six days following phenol injection sclerotherapy for haemorrhoids. He was diagnosed with a phenol-induced hepatitis. Although he remained well, liver function tests only returned to normal after six months. Systemic absorption of phenol has been reported with ingestion, upper airway and excessive cutaneous exposure but not as a complication of haemorrhoidal injection sclerotherapy. Hepatic involvement is also rare and usually the result of ongoing sepsis. We report the unique case of a patient presenting with jaundice secondary to chemical hepatitis, following systemic absorption of phenol at injection sclerotherapy. This case highlights the importance of clinical awareness of not only the infective complications of injection sclerotherapy but also the potential for phenol to be absorbed systemically with severe consequences. A brief overview of symptoms of phenol toxicity is included.
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PMID:Jaundice as a presentation of phenol induced hepatotoxocity following injection sclerotherapy for haemorrhoids. 1578 94

The aim of the present study was to conduct a preliminary investigation into the blood biocompatibility of a novel, uncoated carbon for use in a filtration/adsorption device for the treatment of sepsis. Carbon well prototypes were manufactured from phenol-formaldehyde-aniline-based pyrolysed carbons using monolithic polymer technology. Inflammatory blood cell and plasma protein mediation of the inflammatory response were evaluated using the novel carbon prototypes and compared with dialyser membrane and tissue culture plate controls. Assays determining monocyte and granulocyte adhesion, platelet adhesion and activation, granulocyte activation and complement activation were performed. Preliminary findings suggest an adsorptive but passivating carbon surface. Moderate levels of monocyte and granulocytes adhesion were seen in conjunction with adsorption of plasma proteins to the carbon surface. Activation of granulocyte and adherent platelets was not detected and the complement cascade was not activated by the carbons, indicating a surface compatible with blood contact. The results support the further development of the proposed carbon-based device for the treatment of sepsis.
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PMID:Assessing the in vitro biocompatibility of a novel carbon device for the treatment of sepsis. 1596 98

The gram-positive bacterium Staphylococcus aureus is a major pathogen responsible for a variety of diseases ranging from minor skin infections to life-threatening conditions such as sepsis. Cell wall-associated and secreted proteins (e.g., protein A, hemolysins, and phenol-soluble modulin) and cell wall components (e.g., peptidoglycan and alanylated lipoteichoic acid) have been shown to be inflammatory, and these staphylococcal components may contribute to sepsis. On the host side, many host factors have been implicated in the innate detection of staphylococcal components. One class of pattern recognition molecules, Toll-like receptor 2, has been shown to function as the transmembrane component involved in the detection of staphylococcal lipoteichoic acid and phenol-soluble modulin and is involved in the synthesis of inflammatory cytokines by monocytes/macrophages in response to these components. Nod2 (nucleotide-binding oligomerization domain 2) is the intracellular sensor for muramyl dipeptide, the minimal bioactive structure of peptidoglycan, and it may contribute to the innate immune defense against S. aureus. The staphylococcal virulence factor protein A was recently shown to interact directly with tumor necrosis factor receptor 1 in airway epithelium and to reproduce the effects of tumor necrosis factor alpha. Finally, peptidoglycan recognition protein L is an amidase that inactivates the proinflammatory activities of peptidoglycan. However, peptidoglycan recognition protein L probably plays a minor role in the innate immune response to S. aureus. Thus, several innate immunity receptors may be implicated in host defense against S. aureus.
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PMID:Recognition of Staphylococcus aureus by the innate immune system. 1602 Jun 88

Bacteroides fragilis, which is part of the normal intestinal flora, is a frequent cause of serious disease, especially in diabetic and surgical patients. In these conditions, B. fragilis lipopolysaccharide (LPS) is likely to play a major pathophysiologic role. B. fragilis LPS is structurally different from classical enterobacterial LPS, whose biological activities are mediated by Toll-like receptor 4 (TLR4) activation. The ability of B. fragilis LPS to activate TLR4 and TLR2 was investigated here, since evidence on this issue is scarce and controversial. Each of four different protein-free B. fragilis LPS preparations could induce interleukin-8 responses in cells cotransfected with TLR4/CD14/MD2 but not TLR4/CD14 alone. Two of the preparations also induced cytokine production in cells cotransfected with TLR2/CD14 or in peritoneal macrophages from TLR4 mutant C3H/HeJ mice. Both of these activities, however, were lost after repurification with a modified phenol reextraction procedure. Importantly, all preparations could induce endotoxic shock in TLR2-deficient mice, but not in TLR4 mutant C3H/HeJ mice. Consistent with these findings, anti-TLR4 and anti-CD14, but not anti-TLR2, antibodies could inhibit B. fragilis LPS-induced cytokine production in human monocytes. Collectively, these results indicate that B. fragilis LPS signals via a TLR4/CD14/MD2-dependent pathway, and it is unable to activate TLR2. Moreover, our data document the occurrence of TLR2-activating contaminants even in highly purified B. fragilis LPS preparations. This may explain earlier contradictory findings on the ability of B. fragilis LPS to activate cells in the absence of functional TLR4. These data may be useful to devise strategies to prevent the pathophysiologic changes observed during B. fragilis sepsis and to better understand structure-activity relationships of LPS.
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PMID:Bacteroides fragilis-derived lipopolysaccharide produces cell activation and lethal toxicity via toll-like receptor 4. 1611 79

This study investigated a range of phenol-formaldehyde-aniline-based pyrolysed carbon matrices and their component materials, for their ability to adsorb a range of inflammatory cytokines crucial to the progression of sepsis. The efficiency of adsorption of the target molecules from human plasma was assessed and compared to that of Adsorba 300C, a commercially available cellulose-coated activated charcoal. Results indicate that a number of the primary carbon/resin materials demonstrate efficient adsorption of the cytokines studied here (TNF, IL-6 and IL-8), comparable to other adsorbents under clinical investigation. Our findings also illustrate that these adsorbent capabilities are retained when the primary particles are combined to form a pyrolysed carbon matrix. This capability will enable the engineering of the carbon matrix porosity allowing a blend of carbonised particle combinations to be tailored for maximum adsorption of inflammatory cytokines. The present findings support further investigation of this carbon material as a combined carbon-based filtration/adsorbent device for direct blood purification.
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PMID:The in vitro adsorption of cytokines by polymer-pyrolysed carbon. 1680 58

In ancient India and Persia surgeons were highly respected and their operating skill with nose plastic and catatact couching is documented. In mediaeval Europe surgery was classified as a handicraft profession and belonged to the barbers guild with the soapcup as symbol, much inferior to the academic trained medical doctors. In war surgery leg amputation after shotwounds demanded great rapidity, since no anestetic but alcohol was available. In the 18th century surgeons becamea accepted as medical doctors e.g. John Hunter in London and OlofAcrel in Stockholm. A great step in the development of surgery was Mortons introduction of eter narcosis 1846. Now surgeons could work carefully without hurry. The next step took Joseph Lister. Born in 1827 he studied medicine in London and then qualified as surgeon at the famous James Syme's clinic in Edinburgh- In 1860 he became professor of surgery in Glasgow. His clinic like all others was afflicted with suppuration, septicemia, erysipelas and gangrene. He happened to read a thesis by Louis Pasteur, who proved that fermentation and putrefaction in wine production were caused by bacteria. Lister saw the similarity with wound suppuration. Carbolic acid was used in wood industri to prevent putrefaction and Lister now introduced this as a mean to cure or prevent suppuration and septicemia. He washed the wound and soaked the bandage with carbolic acid, which he also sprayed in the air of the operation theatre to prevent air carried infection. In 1867 he published his experiences in the Lancet: Out of 11 complicated fractures (where the bone-ends penetrated the skin) 9 healed without complications. Earlier such fractures ended with dead or amputation. The wards were now free from infected wounds. Abroad Listers findings were received with entusiasm, Ernst von Bergmann i Berlin modified the antiseptic method into a aseptic one and sterilized the room, the instruments and clothes and could so avoid the carbolic acid spray, which was irritating for the surgeons breath. Lister applied the aseptic method from 1887. Abdominal and thoracic surgery now became possible and developed rapidly. In England his ideas were accepted with some delay. In 1877 he was appointed professor in London, was made a peer and president of the Royal Society nad was celebrated all over the world. He died 1912, 85 years old.
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PMID:[The birth of modern surgery]. 1854 47

Meticillin-resistant Staphylococcus aureus (MRSA) is an important cause of infection, particularly in hospitalized patients and those with significant healthcare exposure. In recent years, epidemic community-associated MRSA (CA-MRSA) infections occurring in patients without healthcare risk factors have become more frequent. The most common manifestation of CA-MRSA infection is skin and soft tissue infection, although necrotizing pneumonia, sepsis and osteoarticular infections can occur. CA-MRSA strains have become endemic in many communities and are genetically distinct from previously identified MRSA strains. CA-MRSA may be more capable colonizers of humans and more virulent than other S. aureus strains. Specific mechanisms of pathogenicity have not been elucidated, but several factors have been proposed as responsible for the virulence of CA-MRSA, including the Panton-Valentine leukocidin, phenol-soluble modulins and type I arginine catabolic mobile element. The movement of CA-MRSA strains into the nosocomial setting limits the utility of using clinical risk factors alone to designate community- or healthcare-associated status. Identification of unique genetic characteristics and genotyping are valuable tools for MRSA epidemiological studies. Although the optimum pharmacological therapy for CA-MRSA infections has not been determined, many CA-MRSA strains remain broadly susceptible to several non-beta-lactam antibacterial agents. Empirical antibacterial therapy should include an MRSA-active agent, particularly in areas where CA-MRSA is endemic.
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PMID:Community-associated meticillin-resistant Staphylococcus aureus infections: epidemiology, recognition and management. 1940 50

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have emerged as serious health threats in the last 15 years. They are associated with large numbers of atopic dermatitis skin and soft tissue infections, but when they originate from skin and mucous membranes, have the capacity to produce sepsis and highly fatal pulmonary infections characterized as necrotizing pneumonia, purpura fulminans, and postviral toxic shock syndrome. This review is a discussion of the emergence of 3 major CA-MRSA organisms, designated CA-MRSA USA400, followed by USA300, and most recently USA200. CA-MRSA USA300 and USA400 isolates and their methicillin-sensitive counterparts (community-associated methicillin-sensitive S aureus) typically produce highly inflammatory cytolysins alpha-toxin, gamma-toxin, delta-toxin (as representative of the phenol soluble modulin family of cytolysins), and Panton Valentine leukocidin. USA300 isolates produce the superantigens enterotoxin-like Q and a highly pyrogenic deletion variant of toxic shock syndrome toxin 1 (TSST-1), whereas USA400 isolates produce the superantigens staphylococcal enterotoxin B or staphylococcal enterotoxin C. USA200 CA-MRSA isolates produce small amounts of cytolysins but produce high levels of TSST-1. In contrast, their methicillin-sensitive S aureus counterparts produce various cytolysins, apparently in part dependent on the niche occupied in the host and levels of TSST-1 expressed. Significant differences seen in production of secreted virulence factors by CA-MRSA versus hospital-associated methicillin-resistant S aureus and community-associated methicillin-sensitive S aureus strains appear to be a result of the need to specialize as the result of energy drains from both virulence factor production and methicillin resistance.
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PMID:Secreted virulence factor comparison between methicillin-resistant and methicillin-sensitive Staphylococcus aureus, and its relevance to atopic dermatitis. 2010 35


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