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)

Plasma kallikrein releases bradykinin when activated by gram-negative septicemia or irreversible hemorrhagic shock. Pancreatitis releases glandular kallikrein causing hypotension and increased vascular permeability. Bradykinin in the brain produces hypertension. Renal kallikrein is released by high arterial pressure, vasodilators, low doses of noradrenaline, angiotensin II, mineralocorticoids and rapid volume expansion. It has a biphasic relation to sodium excretion. In essential hypertension, kallikrein release into the blood and urine is low and facilitates hypertension. High renin in Bartter's syndrome is balanced by high PGE and kallikrein without hypertension.
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PMID:Kallikrein, kininogen and kinins in control of blood pressure. 37 13

Inventarising the inflammatory capacities of the three types of inflammatory cells, PMN, macrophages and mast cells, each type seems able to induce a lethal whole body reaction. This whole body inflammation has hitherto largely escaped our attention, as in clinical studies inappropriate methods have been used such as counting peripheral leucocytes, and as monitoring key-mediators (IL-1, TNF, PGE-2, leukotrienes) and key-cells (activated PMN, macrophages and mast cells) hitherto was impossible. Presently a new set of methods is available, allowing a closer look at this whole body inflammation, such as elastase (monitoring PMN activity), neopterin (monitoring macrophage activity) and hopefully clinically practicable methods to monitor cytokines as well as endotoxin-levels. Only after such comprehensive studies have been performed, it might be concluded that--as in the experimental animal--sepsis and MOF may not necessarily be caused by bacteria or their endotoxins, but by an untoward autodestructive and self-sustaining activation of angry leucocytes and mad macrophages.
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PMID:Multiple organ failure: whole body inflammation? 265 70

The cell walls of gram-negative bacteria contain several biologically active components, including lipopolysaccharide (LPS), lipoprotein, and protein 1. The effects of these individual components and a synthetic analog of lipoprotein, TPP, on several activation parameters of glomerular mesangial cells (MC) were examined. Prostaglandin secretion, synthesis of the autogrowth factor, mesangial interleukin-1 (IL-1), and new synthesis of cellular proteins were assessed as markers of MC activation. All bacterial cell wall components evaluated were active in varying degrees as stimulants of prostaglandin secretion. In general, PGE was the predominant product. TPP and protein 1 also induced substantial secretion of thromboxane. Each cell-wall component was effective in stimulating mesangial IL-1 secretion. The activation of MC was associated with the enhanced synthesis of many cellular proteins in addition to IL-1. Stimulation by these bacterial components was dependent on the state of the mesangial cell cycle, because nonproliferating cells did not respond to these factors. Activation of MC by gram-negative bacterial cell wall components, with release of vasoactive prostaglandins and peptide mitogens, may be responsible for some of the glomerular hemodynamic alterations and cellular proliferative events associated with sepsis or chronic bacterial infection.
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PMID:Activation of glomerular mesangial cells by gram-negative bacterial cell wall components. 305 3

An accepted experimental model for midgut volvulus was used to produce small bowel strangulation obstruction of 48 hours duration in Sprague-Dawley rats. A 93% perioperative mortality rate resulted after release of the volvulus. Treatment with three cytoprotective agents at the time of volvulus release resulted in the following mortality rates: superoxide dismutase, 89%; ibuprofen, 50%; prostaglandin E1 (PGE1, 11%. The predominant cause of death in all treatment groups was bowel infarction, with a smaller number succumbing to either sepsis or circulatory collapse. Concomitant administration of ephedrine or indomethacin to suppress prostaglandin E1's splanchnic vasodilatory activity did not cause any increase in mortality. A trial of aspirin, to simulate PGE's antiplatelet actions, showed no reduction in mortality when compared with detorsion alone. Prostaglandin E1 and, to a lesser extent, ibuprofen, appear to have cytoprotective effects during reperfusion of bowel compromised by volvulus, independent of their influence on the mesenteric vasculature and thrombogenesis.
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PMID:Cytoprotective agents in experimental small bowel volvulus. 355 71

The use of prostaglandins is currently undergoing clinical trials in respiratory failure accompanying sepsis. The effect of prostaglandin E1 (PGE1) and prostacyclin (PGI2) infusion on endotoxin-induced lung injury, with attention to interstitial fluid flux (QL), pulmonary vascular pressure (Ppa), leukocytes, platelets, and release of the lysosomal enzyme beta-glucuronidase, was investigated. A chronic lung lymph fistula model in sheep was used. Seven sheep alternately received Escherichia coli endotoxin and endotoxin plus PGE at a dosage of 1 microgram/kg/min. Six sheep received PGI2 (0.2 microgram/kg/min) instead of PGE1. Both PGE1 and PGI2 decreased the pulmonary hypertension and the interstitial edema produced by endotoxin primarily through their vasodilatory properties. Prostacyclin seemed to have an additional membrane-stabilizing effect. A rebound increase in QL, Ppa, and platelets occurred when PGE1 or PGI2 infusion was discontinued.
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PMID:Prostaglandin infusion and endotoxin-induced lung injury. 703 77

Lipopolysaccharides (LPS) of gram-negative bacteria and superantigens of gram-positive bacteria are among the main causes of sepsis and septic shock. Symptoms are initiated primarily by the release of endogenous mediators, especially cytokines. In the last few years, increasing evidence for the clinical relevance of mixed sepsis caused by coinfections with both types of bacteria has been found. Therefore, we developed an in vitro mixed sepsis model investigating the effect of different superantigen doses, in combination with different LPS concentrations, on cytokine production in human PBMCs using ELISA and RT-PCR. Low, in vivo relevant concentrations of the superantigen toxic shock syndrome toxin-1 (TSST-1) synergistically enhance LPS-induced production of interferon-gamma (IFN-gamma) interleukin-1 beta (IL-1 beta), IL-6, and IL-10, but low LPS has no comparable effect. Signal transduction studies with different inhibitors suggest that this one-way synergism is caused by an interaction between the cAMP and the PIP2 signaling pathway. Furthermore, our findings support the idea that this interaction is one important crossover point of signal transduction pathways by LPS and superantigens, which seems to be predominantly regulated by IFN-gamma and PGE-2. The identification of additional crossover points in the genesis of a mixed sepsis and their selective influence could lead to identical treatment of both gram-negative and gram-positive sepsis.
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PMID:One-way synergistic effect of low superantigen concentrations on lipopolysaccharide-induced cytokine production. 914 52

PGE2-mediated suppression of T cell proliferation during sepsis could result from altered Ca2+ signaling. The present study evaluated the effects of PGE2 on Ca2+ release from intracellular stores and its influx through the plasma membrane in splenic T cells from Sprague-Dawley rats. Intracellular Ca2+ concentration ([Ca2+]i) responses in individual T cells were assessed using the Ca2+ imaging technique, and the release of Ca2+ from intracellular stores and Ca2+ influx were spectrofluorometrically quantified in T cell suspensions. Under unstimulated conditions, nearly 85% of T cells exhibited [Ca2+]i </=50 nM. After stimulation with concanavalin A (Con A), an increase in [Ca2+]i was recorded in approximately 60% of the cells. The pretreatment of T cells with PGE2 had no apparent effect on [Ca2+]i in resting cells; it significantly suppressed the Con A-induced increase in [Ca2+]i in all of the Con A-responsive cells. Ca2+ release from the intracellular stores contributed to the early spike in [Ca2+]i, and the late phase of elevation in [Ca2+]i was dependent on Ca2+ influx through the plasma membrane. Our data suggest that PGE(2) causes an overall suppression of the Con A-induced [Ca2+]i elevation in T cells via inhibiting both Ca2+ influx and its release from the intracellular stores.
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PMID:PGE2 suppresses mitogen-induced Ca2+ mobilization in T cells. 1060 Sep 22

This study was designed to investigate the effects of dietary fish oil on survival rates, plasma amino acid profiles, and inflammatory-related mediators in diabetic rats with sepsis. Diabetes mellitus (DM) was induced in rats by streptozotocin. The DM rats were maintained for 4 weeks on medium fat (10%, w/w) diets containing either fish oil or safflower oil. After that, sepsis was induced by cecal ligation and puncture (CLP). There were 2 groups in this study: fish oil sepsis group (FOS) and safflower oil sepsis group (SOS). The survival rate was observed after CLP. Also, changes of the amino acid pattern as well as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, prostaglandin (PG) E(2)at 6, 12, and 24 h after CLP were investigated. The results demonstrated that survival rates were not significantly different between the 2 groups. Plasma arginine levels were significantly lower in sepsis groups than that in the DM-chow group, regardless of whether the diabetic rats were fed fish oil or safflower oil. No significant differences were observed in plasma valine, leucine, isoleucine, glutamine, or arginine concentrations between the FOS and SOS groups at different time points. Concentrations of IL-1 beta in peritoneal lavage fluid (PLF) at 6 h and TNF-alpha at 6 h as well as at 12 h after CLP in the FOS group were significantly higher than those in the SOS group. PGE(2)levels in PLF, by contrast, were lower in the FOS group at 6 and 12 h after CLP than in the SOS group. These results suggest that differences in IL-1 beta, TNF-alpha, and PGE(2)levels in PLF in the early period of sepsis did not influence the survival rates and plasma amino acid profiles of the FOS and SOS groups. Compared with safflower oil, feeding diabetic rats with fish oil had no beneficial effects on survival rates and muscle protein breakdown. The immunologic impact of dietary n-3 polyunsaturated fatty acids on diabetic rats with sepsis requires further investigation.
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PMID:Effects of dietary fish oil on survival rate, plasma amino acid pattern, and inflammatory-related mediators in diabetic rats with sepsis. 1103 Oct 68

Studies have shown gender dimorphism in cell-mediated immune responses following haemorrhage, with depressed responses in young males and maintained or enhanced responses in proestrus females. However, it remains unknown whether or not the sexually dimorphic immune response to haemorrhage provides any protection against a subsequent in vivo polymicrobial septic challenge. To study this, male and proestrus female C3H/HeN mice were subjected to haemorrhage (35+/-5 mmHg for 90 min followed by fluid resuscitation) or sham operation. Twenty-four hours thereafter, all mice were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP) and survival was assessed over a 10 day period. Haemorrhage prior to CLP significantly increased mortality in males as compared to shams. In contrast, mortality in females following CLP was comparable between the sham and haemorrhage groups. Plasma levels of interleukin (IL-)6, tumour necrosis factor (TNF)-alpha and prostaglandin E(2)(PGE(2)) at 5 h after CLP were significantly increased in males subjected to prior haemorrhage. In contrast, plasma levels of IL-6 and TNF-alpha in females did not increase under such conditions. PGE(2)levels were comparable in males and females following CLP, however prior haemorrhage significantly reduced PGE(2)levels in females, whereas no change was observed in males. Liver and splenic expression of cyclooxygenase-2 protein paralleled the changes in plasma PGE(2). Female sex hormones, therefore, appear to play an important role not only in maintaining immune function following haemorrhage, but also provide a survival advantage against subsequent septic challenge.
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PMID:Gender differences in the inflammatory response and survival following haemorrhage and subsequent sepsis. 1139 94

Trauma causes the release of anti-inflammatory factors thought to cause infections by inhibiting T cells. We have found that hypertonic saline (HS) enhances functions of normal T cells. Here we studied if HS can rescue T cells from suppression by costimulating interleukin (IL)-2 production. Human peripheral blood mononuclear cells were treated with the immunosuppressive factors IL-4, IL-10, transforming growth factor (TGF)-beta(1), and PGE(2) and with serum of trauma patients and stimulated with phytohemagglutinin, and IL-2 production was measured. Costimulation with HS tripled IL-2 production of normal cells. IL-4, IL-10, TGF-beta(1), and PGE(2) suppressed IL-2 production with IC(50) of 500, 1, 36,000, and 0.01 pg/ml, respectively. Costimulation of suppressed cells with HS restored IL-2 production and increased IC(50) values >70-fold. Serum from trauma patients could completely suppress normal cells; however, costimulation with HS restored IL-2 production by up to 80% of the control response. These findings show that HS can restore the function of suppressed T cells, suggesting that HS resuscitation of trauma patients could reduce posttraumatic sepsis.
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PMID:Hypertonicity rescues T cells from suppression by trauma-induced anti-inflammatory mediators. 1150 61


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