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)

The purpose of this prospective study was to characterize kininogens in plasma from surgical ICU patients. Thirty-five patients, ages 19-79 years, were divided into 2 groups: sepsis (defined by standard criteria) and nonsepsis. Studies of proteolytic degradation of H-kininogen showed degradation in both patient groups compared to healthy controls. Functional quantification of prekallikrein showed a reduction of prekallikrein in plasma from both patient groups. Functional quantification of kininogens by a CPI (cysteine proteinase inhibitor) assay showed no significant differences between the patients and the controls. Immunological levels of H-kininogen and total kininogen were not significantly different from normal plasma. No differences could be detected between the two patient groups in any of the parameters studied. In conclusion, this study supported contact activation taking place in surgical ICU patients, a partial kinin release and a consumption of prekallikrein has taken place in vivo.
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PMID:Bradykinin release from high molecular weight kininogen in surgical ICU patients. 885 88

Endothelium-dependent hyperpolarizing factor (EDHF) is an important contributor to agonist-induced vascular dilation. Recent studies suggest that bacterial lipopolysaccharides attenuate endothelium-dependent dilation. Whether or not this effect is mediated through inhibition of EDHF is not known. We studied the in vitro influence of Escherichia coli lipopolysaccharides on endothelium-dependent smooth muscle dilation and hyperpolarization in porcine coronary arteries. Endothelium-intact porcine coronary arterial rings were examined after 20 h of incubation with either saline or E. coli lipopolysaccharides (100 microg/ml). Endothelium-dependent dilation elicited by increasing concentrations of bradykinin was significantly attenuated by lipopolysaccharides. Baseline values of smooth muscle membrane potential were not influenced by lipopolysaccharides. However, lipopolysaccharides significantly attenuated bradykinin-induced smooth muscle membrane hyperpolarization. Our results suggest that attenuation of EDHF is an important mechanism through which lipopolysaccharides influence vascular dilation in severe sepsis.
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PMID:Attenuation of endothelium-dependent hyperpolarizing factor by bacterial lipopolysaccharides. 920 71

A sequence of 31 amino acids (S565-K595) in domain 6 of the light chain of high molecular weight kininogen (HK) has previously been shown to be responsible for the binding of plasma prekallikrein (PK) or kallikrein. To find effective peptides that might block binding between HK and PK on cell surfaces, a new series of synthetic peptides has now been prepared that incorporates portions of this binding domain sequence. For mapping the minimal sequence within HK, these new peptides were tested for their ability to compete with HK for binding PK in a cell-free system and on human umbilical vein endothelial cells (HUVEC). In the former, at pH 7.4, the kds for binding between kallikrein and either D567-K595, S565-P594, D567-S593, or D567-T591 were all similar to that for the binding of S565-K595 (0.2 to 0.4 micromol/L), but those for the binding of D568-K595, W569-K595, and D567-P589 were an order of magnitude greater (kd = 2 to 5 micromol/L). D567-S586, the shortest chain length of the N- and C-terminal truncation sequences tested, does not effectively compete with kininogen for kallikrein binding (kd = 100 micromol/L). These results imply that D567-T591, a 25-residue peptide (HK25c), contains sufficient structural information for binding kallikrein in solution. D567-T591 also is the minimum structural sequence to block binding of kallikrein to HUVEC-bound HK (IC50 = 50 nmol/L) and to inhibit PK activation to kallikrein on the cell surface (IC50 = 80 nmol/ L). In addition, D567-T591 also inhibits the generation of kallikrein-activated urokinase, which activates plasminogen to plasmin (IC50 = 100 nmol/L). Thus, HK-derived peptides may be useful compounds for modulating excessive fibrinolysis and hypotension in sepsis and multiple trauma.
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PMID:High molecular weight kininogen peptides inhibit the formation of kallikrein on endothelial cell surfaces and subsequent urokinase-dependent plasmin formation. 922 69

HK31 (S565-K595) has previously been shown to encompass the binding domain for plasma prekallikrein (PK) within domain 6 of high molecular weight kininogen (HK). The complementary binding domain for HK within PK is mapped to PK56 (F56-G86), in the Apple 1 domain and to PK266 (K266-C295) in the Apple 4 domain. Isothermal titration calorimetry demonstrated that either PK peptide binds to HK31 in 1:1 stoichiometry. Binding of the alternate PK peptide into a ternary complex is facilitated nearly 2-fold. Fluorescence emission spectroscopy revealed that only the binding of PK56 caused a limited decrease in intrinsic tryptophane fluorescence emission intensity of HK31. We conclude that the two PK peptides bind to the HK peptide at different sites. To map the minimal sequence within HK31, truncated new peptides were tested for their ability to compete with HK for binding PK in a cell-free system. D567-T591, a 25-residue peptide which contains sufficient structural information for binding kallikrein in solution, blocked the binding of kallikrein to HK bound to endothelial cells and inhibited PK activation to kallikrein and the generation of kallikrein-activated urokinase on endothelial cell surfaces. HK-derived peptides could modulate excessive fibrinolysis and hypotension in sepsis and multiple trauma.
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PMID:Physical and biological significance of peptide sequences mediating the interaction between high molecular weight kininogen and plasma prekallikrein. 922 46

Involvement of bradykinin generation in bacterial invasion was examined by using a gram-negative bacillus, Vibrio vulnificus, which is known to invade the blood circulatory system and cause septicemia. V. vulnificus was injected intraperitoneally (i.p.) into mice with or without bradykinin or a bradykinin (B2 receptor) antagonist. Dissemination of V. vulnificus from peritoneal septic foci to the circulating blood was assessed by counting of viable bacteria in venous blood by use of the colony-forming assay. Intravascular dissemination of V. vulnificus in mice was significantly potentiated by simultaneous injection with bradykinin but was markedly reduced by coadministration with the B2 antagonist D-Arg,[Hyp3, Thi(5,8), D-Phe7]-bradykinin. Furthermore, V. vulnificus lethality was significantly increased when bradykinin was administered simultaneously with the bacillus, whereas it was definitely suppressed by treatment with D-Arg,[Hyp3, Thi(5,8), D-Phe7]-bradykinin. Similarly, ovomacroglobulin, a potent inhibitor of the V. vulnificus protease, showed a strong suppressive effect on the V. vulnificus septicemia. We also confirmed appreciable bradykinin production in the primary septic foci in the mouse peritoneal cavity after i.p. inoculation with V. vulnificus. It is thus concluded that bradykinin generation in infectious foci is critically involved in facilitation of intravascular dissemination of V. vulnificus.
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PMID:Involvement of bradykinin generation in intravascular dissemination of Vibrio vulnificus and prevention of invasion by a bradykinin antagonist. 945 58

Fever, hypotension and bleeding disorders are common symptoms of sepsis and septic shock. The activation of the contact-phase system is thought to contribute to the development of these severe disease states by triggering proinflammatory and procoagulatory cascades; however, the underlying molecular mechanisms are obscure. Here we report that the components of the contact-phase system are assembled on the surface of Escherichia coli and Salmonella through their specific interactions with fibrous bacterial surface proteins, curli and fimbriae. As a consequence, the proinflammatory pathway is activated through the release of bradykinin, a potent inducer of fever, pain and hypotension. Absorption of contact-phase proteins and fibrinogen by bacterial surface proteins depletes relevant coagulation factors and causes a hypocoagulatory state. Thus, the complex interplay of microbe surface proteins and host contact-phase factors may contribute to the symptoms of sepsis and septic shock.
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PMID:Activation of the contact-phase system on bacterial surfaces--a clue to serious complications in infectious diseases. 950 May 98

Various autacoids, including the eicosanoids, platelet activating factor (PAF) and bradykinin, have been implicated in the pathogenesis of sepsis and septic shock. The precise role of these compounds as mediators of the diffuse inflammatory state characteristic of sepsis remains to be determined, but, in animal models, beneficial effects have been observed as a result of treatment with various inhibitors of eicosanoid biosynthesis or antagonists of PAF or bradykinin receptors. To date, however, it has been impossible to translate these encouraging results from animal models into convincingly positive results in the clinical setting.
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PMID:Therapeutic options directed against platelet activating factor, eicosanoids and bradykinin in sepsis. 951 Oct 90

Sepsis, septic shock, and multiple organ dysfunction are heterogeneous and sophisticated clinical syndromes which result from the interplay of mediators of cellular function and inflammation. Secondary mediators such as lipids (prostaglandin, thromboxane, platelet-activating factor), peptides (bradykinin, vasoactive intestinal peptide), amines (histamine, serotonin) and complements are key mediators which lead to the state of shock in human sepsis. Endotoxin may also cause multiple organ dysfunction syndrome (MODS). New antiendotoxin treatment and the strategy for sepsis including endotoxemia are reviewed. Monoclonal antibodies directed at core epitopes and lipid A (E5, HA1-A) could not reproduce the beneficial effects. Bactericidal/permeability increasing protein (BPI)). Endotoxin neutralizing protein (ENP)) and E5531 may have potential in the treatment of sepsis. Another treatment using extracorporeal endotoxin removal is reported. Polymyxin B immobilized fiber (PMX), commercialized as Toraymyxin, is now widely used in Japan for severe sepsis and septic MODS. PMX treatment improves the symptoms related to the septic state, a hemodynamic disorders, and cytokine levels including tumor mecrosis factor, interleukin (IL)-6, and IL-10, with a decrease in endotoxin levels. Phase II, III, and IV clinical trials with extracorporeal endotoxin removal by PMX revealed that endotoxin removal is helpful in the treatment of septic patients.
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PMID:[Sepsis and organ failure--its pathogenesis and treatment]. 978 88

To study whether a sepsis-induced increase in des-Arg9-bradykinin (des-Arg9-BK) and bradykinin (BK) B1-receptor activity participates in the observed increase in pulmonary vascular resistance in neonatal group B streptococcal sepsis (GBS), isometric force bioassays of pulmonary artery (PA) rings were studied, after 4-h exposure to either Krebs or GBS, by using the following protocols: 1) BK dose-response curve, 2) vascular response to BK with NG-nitro-L-arginine methyl ester (L-NAME), and 3) response to des-Arg9-BK (BK metabolite and B1 agonist). PA rings exposed to BK resulted in contraction in the GBS group and a decrease in resting tension in the Control group (P = 0.034) at a concentration of 10(-5) M. GBS-treated PA rings contracted more to des-Arg9-BK than did Controls (P < 0.001). BK (10(-6) M) relaxed preconstricted PA rings incubated in GBS less than BK relaxed Controls (P < 0.001), and preincubation with L-NAME decreased relaxation in both. These results suggest that GBS decreased endothelium-dependent BK relaxation and increased contractile response to des-Arg9-BK. We speculate that this occurs secondary to upregulation of B1 receptors reflected by B1-agonist-mediated PA contraction.
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PMID:Influence of group B streptococci on piglet pulmonary artery response to bradykinin. 988 13

Pericytes are contractile cells of the microvasculature which may contribute to the hypotension and increase in permeability that are present during inflammation and late-stage sepsis. The purpose of this study was to examine the contractile effects, if any, of septic modulators on the lung pericyte. Contractile effects were qualitatively examined using a previously developed silicone rubber method. This study further demonstrates a quantitative method for measuring the contraction of lung pericytes cultured on a collagen lattice. Contraction was measured by the change in collagen matrix area in response to vasoactive stimuli. Bradykinin and serotonin significantly increased contraction in a dose-dependent manner, with a maximum increase in contraction twice that of control. Forskolin and adenosine caused relaxation, also in a significant dose-dependent manner, with a maximum decrease in contraction of 80 and 30-40%, respectively. Histamine had no effect on contractility in either the silicone rubber or the collagen lattice assay. These results show that the lung pericyte, like the retinal pericyte, is a contractile cell and can be stimulated to contract or relax in vitro by the presence of certain inotropic agents present during inflammation and sepsis. These responses may play a role in microvascular regulation.
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PMID:Effects of vasoactive mediators on the rat lung pericyte: quantitative analysis of contraction on collagen lattice matrices. 1004 61


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