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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Continuous i.v. infusion of a nonlethal dose of Escherichia coli endotoxin induced an early (3-h) accumulation of neutrophils in the rat liver followed by a later (30-h) greater extravasation of mononuclear phagocytes (MNP). These inflammatory cells, recovered together by centrifugal elutriation, were analyzed for their potential capacity to metabolize [1-14C]-AA. Ca2+ ionophore A23187 (5 microM) stimulated the release of [1-14C]-AA from PC and PI both in cells from saline- and ET-infused rats, the latter showing a higher capacity to further metabolize AA to eicosanoids. LTB4 and 5-HETE were the major metabolites accumulated in cells from rats infused with ET for 3 h, while PGD2 played the main role in cells from saline-infused rats. This could reflect [1-14C]-AA metabolism by PMNP and Kupffer cells, respectively. By 30 h of ET-infusion, a shift from PGD2 to PGE2 release was observed. These results suggest that eicosanoids released by nonparenchymal cells (i.e., Kupffer and endothelial cells) and PMNP in the liver of ET-infused rats may alter the normal intercellular information flow between parenchymal and nonparenchymal cells, contributing to the severe impairment in liver function and metabolism during endotoxicosis and sepsis.
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PMID:Eicosanoid production in nonparenchymal liver cells isolated from rats infused with E. coli endotoxin. 217 32

Cachexia in tumour-bearing patients involves loss of skeletal muscle proteins. In order to elucidate the mechanisms underlying this phenomenon, we tested the hypothesis of the presence of a circulating proteolytic factor (possibly interleukin-1, acting through an increased PGE2 release) in the plasma of cancer patients, because such a mechanism has been demonstrated in patients with sepsis or trauma and in animals with bacteraemia or viraemia. The effect of plasma from 13 malnourished cancer patients and 14 controls on PGE2 release and protein degradation (assessed as Tyr release) in rat diaphragm in vitro was evaluated; human recombinant interleukin-1 alpha (IL-1) was used for comparison. IL-1 increased PGE2 release (+44% at 5 U/ml), but did not greatly affect proteolysis. On the contrary, human plasma (125 microliters/ml) from both control and tumour-bearing individuals did not affect PGE2 release significantly, but greatly reduced Tyr release. The decrease in Tyr release by plasma was dose-dependent. In conclusion, our data indicate that, at variance with what was demonstrated in patients with trauma or sepsis, loss of skeletal muscle proteins in cancer patients is not mediated by a circulating factor. In addition, evidence is provided of dissociation between PGE2 and Tyr release and of lack of proteolytic activity for IL-1.
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PMID:Effect of plasma from cancer patients on rat skeletal muscle protein degradation and PGE2 release in vitro. 233 Mar 45

Thirty multiply injured blunt-trauma patients at high risk for development of ARDS (multisystem trauma including more than one organ or extremity, Injury Severity Score of 26 or more, hypotension and need for 1500 mL or more blood within the first hour after admission, and PaO2 less than or equal to 70 torr) were studied sequentially with blood and physiologic evaluations beginning immediately after injury and every eight hours for eight days, or until death, to study the evolution of the ARDS process. Mixed venous blood samples were obtained for eicosanoids PGE2, PGF2 alpha, thromboxane B2, PGI2 (6-KetoPGF1 alpha) and leukotriene B4 (LTB4). Platelet (PLAT), and neutrophil (WBC) counts were also done and plasma elastase was measured. At 7:00 AM each day patient neutrophils were obtained for a study of zymosan-activated superoxide production using a chemiluminescence assay. These data were correlated with physiologic measurements of the Respiratory Index (RI), per cent pulmonary shunt (QS/QT), and respiratory compliance measures. Seven patients developed a fulminant post-traumatic ARDS syndrome within 96 hours after injury. Twelve patients without ARDS developed sepsis (TS) four or more days after injury, and 11 had uncomplicated postinjury courses (TR). Compared to both TR and TS, ARDS had a significant (p less than 0.01) rise in neutrophil superoxide production beginning on day 2 through day 4 after injury. This was preceded by rises in PGE2 and LTB4, which were significantly correlated with subsequent falls in PLAT and WBC and rises in TXB2, PGF1, and superoxide production and followed by increases in RI, QS/QT, and a fall in compliance. The significant difference in the pattern and sequence of events in ARDS compared to TR and TS patients suggests that in ARDS the earliest event may be related to peripheral release of PGE2 and LTB4 due to platelet activation and lung sequestration with release of PGF2 alpha, and by aggregation and leukocyte adherence with release of elastase. However, fulminant ARDS mortality appears to be related to the subsequent amplification of the LTB4 leukocyte activation with superoxide production that does not achieve significance before the second day after injury and rises to a maximum by day 4 after injury. These data suggest that post-trauma ARDS follows a different evolutionary pattern than that reported in animal models and is also different from that seen in human TS or TR patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sequential patterns of eicosanoid, platelet, and neutrophil interactions in the evolution of the fulminant post-traumatic adult respiratory distress syndrome. 254 91

Patients suffering severe trauma, including thermal injuries, demonstrate both a hypermetabolic response and an immunosuppressed state following the injury. Biochemically, these patients produce extremely large amounts of cyclooxygenase products, including prostaglandin E. We have investigated the effect of a drug, ibuprofen, which blocks the synthesis of prostaglandins in a burned rat model. Ibuprofen at high doses was found to significantly diminish the hypermetabolic response to burn injury and sepsis. The same dosage of ibuprofen increased the mortality rate in the same burn sepsis model. Prostaglandin E may therefore exert some beneficial effects in traumatized patients by altering their metabolism.
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PMID:The effect of ibuprofen on postburn metabolic and immunologic function. 278 85

A case report of a ligamentary ectopic pregnancy that failed to respond to prostaglandin E2 for induced abortion for sepsis at 24 weeks is presented. The 27-year-old nullipara had normal ultrasound findings for gestational age up to 21 weeks gestation. She had consulted at 5 weeks for abdominal pain and bleeding, at 14 weeks again for abdominal pain, shoulder pain and vaginal bleeding, although both times the pain and bleeding resolved spontaneously. She was seen again at 16 and 21 weeks gestation, when ultrasound scans were normal for dates. At 24 weeks, she experienced vaginal discharge of blood and tissue, and was managed as premature rupture of membranes. She became septic 12 days later. She was treated with transcervical PGE2 and iv oxytocin without response for 3 days. Surgical evacuation was successful, but bleeding persisted. During laparotomy she had a large left broad ligament hematoma, a left ruptured uterus, and open left internal iliac artery and vein. These were repaired, and she received 40 units of blood, 8 platelets and 14 of plasma. Only after histology was the diagnosis of ligamentary pregnancy made. The lack of response to PG for abortion should raise suspicion of ectopic pregnancy, although preoperative diagnosis of ligamentary pregnancy is extremely rare.
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PMID:A rare gynecologic contraindication to the use of prostaglandins and oxytocin to induce abortion. A case report. 279 68

Prostaglandin E2 (PGE2) reportedly increases protein break-down in skeletal muscle. The role of PGE2 for accelerated muscle proteolysis during sepsis, however, is controversial. In this study, the effect of the prostaglandin synthesis inhibitor indomethacin on PGE2 release and protein breakdown in skeletal muscle from nonseptic and septic rats was evaluated. Sepsis was induced in male Sprague-Dawley rats (40-60 g) by cecal ligation and puncture (CLP). After 16 hours the extensor digitorum longus (EDL) and soleus (SOL) muscles were dissected with intact tendons and incubated in an oxygenated medium, and the release of tyrosine (protein breakdown) and PGE2 into the incubation medium was determined. Paired muscles were incubated in the absence or presence of indomethacin (3 mumol/L or 6 mumol/L). In some experiments the effect of indomethacin was investigated in the presence of different concentrations of insulin (1, 10, or 100 mU/mL) since previous reports suggested an interaction between insulin and prostaglandins on protein turnover in skeletal muscle. In other experiments muscles were incubated in a flaccid or stretched state, which is known to influence the metabolic response to different substances. Protein breakdown rate was 0.210 +/- 0.013 and 0.492 +/- 0.025 mumol Tyr/g X 2 hours in EDL from nonseptic and septic rats, respectively (p less than 0.01). The corresponding values for SOL were 0.480 +/- 0.037 and 0.712 +/- 0.039 mumol Tyr/g X 2 hours (p less than 0.01). Addition of indomethacin to the incubation medium reduced PGE2 release from 29.1 +/- 3.1 to 6.8 +/- 0.7 ng/g X 2 hours in nonseptic SOL and from 50.6 +/- 10.4 to 5.6 +/- 0.7 ng/g X 2 hours in septic SOL. Protein breakdown rate in SOL and EDL from sham-operated or septic rats was unaffected by indomethacin, both when muscles were incubated in a flaccid or stretched state, and when they were incubated in the presence or absence of insulin. The present results do not suggest a role of PGE2 for accelerated muscle proteolysis in the present experimental septic model.
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PMID:Further evidence that accelerated muscle protein breakdown during sepsis is not mediated by prostaglandin E2. 316 71

During sepsis or after injection of endotoxin into rats, there is a large increase in muscle protein breakdown and prostaglandin E2 (PEG2) production. Prior studies showed that partially purified interleukin 1 (IL-1) from human monocytes can stimulate these processes when added to isolated rat muscles. The availability of pure recombinant IL-1 and other monokines has allowed us to investigate the identity of the active agent in this process. Incubation of muscles with recombinant human or murine IL-1 alpha or IL-1 beta or with IL-1 plus a phorbol ester did not stimulate muscle proteolysis or PGE2 production. Homogeneous natural porcine IL-1 ("catabolin") and mouse or human IL-1 beta were also not effective in vitro. In addition, a variety of other human cytokines, including tumor necrosis factor ("cachectin"), epidermal thymocyte-activating factor, eosinophil cytotoxicity-enhancing factor, interferon-alpha, beta, and gamma, platelet-derived growth factor, and transforming growth factor (TGF) beta, which are all released by activated macrophages, TGF-alpha, or mixtures of these polypeptides, also failed to activate proteolysis or PGE2 production. By contrast, a large increase in net protein breakdown could be induced in the rat soleus by polypeptides released from porcine monocytes or by the serum from febrile cattle which had been injected with Pasteurella haemolytica or bovine rhinotracheitis virus. Therefore, a still-unidentified product of activated monocytes appears to be responsible for the negative nitrogen balance that accompanies infectious illness.
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PMID:Activation of protein breakdown and prostaglandin E2 production in rat skeletal muscle in fever is signaled by a macrophage product distinct from interleukin 1 or other known monokines. 328 11

Inhibited amino acid transport in skeletal muscle during sepsis has been demonstrated previously. In the present study we investigated the effects in vitro of plasma from septic animals or fractions of septic plasma that contain solutes with a molecular weight less than 30,000 daltons or less than 2000 to 3000 daltons on amino acid transport in incubated rat soleus (SOL) muscles. The influence of interleukin-1 (IL-1), prostaglandin E2 (PEG2), and the "catabolic" hormones corticosterone, glucagon, and epinephrine on muscle amino acid uptake was also investigated. Amino acid transport was studied with 3H-alpha-aminoisobutyric acid (AIB). Whole-septic plasma and the two low molecular-weight fractions of the septic plasma reduced muscle amino acid uptake by about 20%. IL-1 or PGE2 did not affect amino acid transport. When the catabolic hormones were added individually to incubated SOL muscles, no changes in AIB uptake were noticed. When glucagon or epinephrine was added in combination with corticosterone or when all three hormones were added together, amino acid transport was reduced by 10% to 15%. The results suggest that inhibited muscle amino acid uptake in sepsis is caused by a circulating factor(s) with a molecular weight less than 2000 to 3000 daltons. A synergistic action among the catabolic hormones may be one important factor for reduced muscle amino acid transport in sepsis.
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PMID:Reduced muscle amino acid uptake in sepsis and the effects in vitro of septic plasma and interleukin-1. 348 96

Recent interest in the role of prostaglandin inhibitors as immunomodulators following major injury prompted us to study the effect of indomethacin on burn-induced immunosuppression in rats as measured by the delayed-type hypersensitivity (DTH) skin test response, ability to contain an intradermal bacterial challenge (10(8) Staphylococcus aureus 502A injected intradermally), and overall survival from spontaneous burn wound sepsis. Fifty male Sprague-Dawley rats sensitized to keyhole limpet hemocyanin (KLH) were subjected to a 30% full-thickness scald burn. Group 1 (n = 24) received indomethacin at 0.5 mg/kg intraperitoneally once daily with the first dose given immediately following the burn. Group 2 (n = 24) received vehicle only. Prostaglandin E2 measured by radioimmunoassay on day 17 was 2553 +/- 832 pcg/ml serum (+/- SEM) in the vehicle group and 1042 +/- 231 pcg/ml in the indomethacin group (P = 0.058, unpaired t test). Burn injury induced a decrease in the DTH response to KLH and an increase in the Staph lesion size (P less than 0.05) which was not corrected by indomethacin treatment. All animals developed spontaneous burn wound sepsis by day 14. Survival after 17 days in the indomethacin group was 100% compared to that of the vehicle group, 79%, P less than 0.05 (Fisher exact test). We conclude that despite unmeasurable corrections of the burn-induced suppression of the DTH response and local nonspecific bacterial defenses, low-dose indomethacin improves survival following burn sepsis.
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PMID:The effect of indomethacin on burn-induced immunosuppression. 362 43

Hypoimmunity after major trauma and thermal injury appears to predispose to septicemia. An increase of immune suppressive T cells and the inhibitory monocytes product PGE2 has been demonstrated postburn and are suggested as contributing to postburn hypoimmunity. TP5, the biologically active part of thymopoientin, has an immunomodulating effect on T cells. Indomethacin, an irreversible blocker of the prostaglandin synthesis has been suggested to reduce the inhibitory monocytes-mediated immunosuppression. In this study strains 2 and 13 guinea pigs received 20-30% TBSA scald burn and were subsequently injected with either TP5 or indomethacin or a combination of both on the 3 following days postburn. The ability of splenocytes to produce a secondary immune response to SRBC was measured in the in vitro AFC assay. The animals who had received TP5 and indomethacin showed significant improvement in their ability to mount an immune response in the AFC assay.
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PMID:The immunomodulating effect of TP5 and indomethacin in burn-induced hypoimmunity. 623 2


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