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

Pentoxifylline (PTX), a methylxanthine, can suppress polymorphonuclear leukocyte (PMN) activation and attenuate sepsis-induced acute lung injury. We investigated whether PTX prevents non-PMN-dependent lung injury. First we studied four groups of granulocyte-depleted guinea pigs (control, PTX, Escherichia coli, and E. coli + PTX). Lung injury was assessed by wet-to-dry lung weight (W/D) ratio and lung tissue-to-plasma 125I-albumin ratio (albumin index, AI). The E. coli group showed a significant increase in the lung W/D ratio and AI compared with the control and PTX groups. However, PTX did not prevent the E. coli-induced increase in the lung W/D ratio and AI. Next we investigated the effects of PTX on endothelial cell monolayer permeability and adenosine 3',5'-cyclic monophosphate (cAMP) levels. Whereas E. coli lipopolysaccharide (LPS) alone increased the endothelial permeability, PMNs added to the endothelial monolayers and exposed to LPS enhanced the increase. PTX attenuated the permeability increase mediated by LPS-exposed PMNs. PTX did not prevent the LPS-induced increase in permeability when PMNs were not present, although PTX increased endothelial cell cAMP levels. These data demonstrate that 1) PTX does not prevent lung injury in granulocyte-depleted guinea pigs; 2) PTX does not prevent LPS-induced increases in endothelial cell permeability, despite increased cAMP levels; and 3) PTX attenuates PMN-dependent increases in endothelial cell permeability.
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PMID:Pentoxifylline does not attenuate acute lung injury in the absence of granulocytes. 165 91

The acute-phase response that follows injury and sepsis is characterized by increased hepatic synthesis of specific secreted proteins while production of albumin is decreased. The effect of burn injury on specific synthesis rates of secreted hepatic proteins has not been reported. In this study, Sprague-Dawley rats received either a 30% flame burn (n = 12) or a sham burn (n = 12) and were allowed to recover for 11 days. Burned animals showed slower weight gains and a 25% to 30% higher resting energy expenditures compared with controls. On postburn day 11, synthesis of secreted hepatic proteins was measured by incorporation of leucine during a 2-hour isolated liver perfusion. Synthesis of total secreted proteins, the seromucoid fraction, and complement component C3 was significantly increased in burned animals, whereas synthesis of albumin was unaltered. In spite of unchanged albumin synthesis, plasma albumin concentrations were 50% lower in burned animals than in control animals throughout the postburn period. These findings suggest that decreased albumin synthesis is not the only mechanism responsible for persistent hypoalbuminemia that follows burn injury.
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PMID:Synthesis of albumin and acute-phase proteins in perfused liver after burn injury in rats. 170 76

The effect of ischemia on hepatic protein synthesis during sepsis is not known, but is of clinical relevance, since hepatic blood flow decreases during the late phase of sepsis. In this study, synthesis of acute-phase proteins was measured in perfused livers of rats 16 hours after sham operation or cecal ligation and puncture. Livers from each group had 45 minutes of complete ischemia or control perfusion. Protein synthesis was measured during two hour perfusion after the ischemia or control period, by determining incorporation of 3H-leucine into total secreted trichloracetic acid precipitated proteins, immunoprecipitated complement component C3 and albumin and phosphotungstenate-precipitated alpha 1-acid glycoprotein. Lactate, glutamine-oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels in the perfusate were measured during preischemic and postischemic perfusion. Tissue glutathione levels were measured at the end of the perfusion. Synthesis of alpha 1-acid glycoprotein was increased by 100 per cent and albumin synthesis decreased by 46 per cent in septic livers, consistent with an acute-phase response and apparent downregulation of albumin synthesis during early sepsis. Synthesis rates were reduced by 50 to 60 per cent after ischemia in perfused livers from sham operated rats and 70 to 80 per cent in livers from septic rats. Hepatic production of interleukin-1 was not different between the groups during perfusion. GOT and GPT levels increased significantly during ischemia of both nonseptic and septic livers and rapidly returned toward baseline during reperfusion. Lactate levels were higher in perfusate of septic than of nonseptic livers before ischemia and increased further during ischemia. The results suggest that ischemia inhibits production of secreted hepatic proteins similarly in nonseptic and septic livers, but perhaps to a slightly greater extent in septic livers.
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PMID:Effect of ischemia on protein synthesis in the septic liver. 170 61

The administration of branched-chain amino acids (BCAAs) has been proved useful in reducing both urea nitrogen production and muscle proteolysis in trauma patients with sepsis, but the optimum infusion rate to achieve these effects is still in question. In this prospective randomized study, a group of 16 posttrauma patients with sepsis received a branched chain-enriched (BCAA = 49.4%) amino acid mixture (8 patients; 120 observations) or a standard amino acid infusion (BCAAs = 15.5%; 8 patients; 227 observations). Total calories, percent lipid calories, and amino acid nitrogen administration were not different in the two groups. Each patient was studied at 8-hour intervals for the plasma levels of amino acids, six hepatic acute-phase proteins, albumin, and other metabolic parameters, including urinary urea nitrogen and 3-methylhistidine excretion. The total intake of each amino acid and its clearance were calculated and the dose of leucine during each 8-hour period was related to the leucine clearance, plasma acute-phase protein levels, and the urinary production of urea and 3-methylhistidine, as an indicator of proteolysis. The results show a significant (r2 = 0.691; p less than 0.0001) reduction of urea nitrogen production and proteolysis as a function of the increase in leucine dose. The identification of a critical mean rate of leucine infusion has been derived from the analysis of the significant linear correlation between leucine intake and leucine clearance (r2 = 0.594; p less than 0.0001). Significant positive correlations between the leucine intake dose and the platelet count (r2 = 0.402; p less than 0.0001), the plasma fibrinogen level (r2 = 0.218; p less than 0.0001), and the regression-derived sum of six acute-phase proteins plus albumin (r2 = 0.696; p less than 0.0001) were found. The increase in leucine clearance was progressively less marked above a mean daily leucine intake rate of 1.4 mumol/kg/min, which also appeared to be the dose level that maximized the acute-phase protein and coagulation effects and reduced proteolysis and urea nitrogen production, suggesting that this is a critical BCAA infusion rate at which an optimum leucine effect occurs. From these data a BCAA (leucine) dose nomogram has been derived.
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PMID:Leucine dose response in the reduction of urea production from septic proteolysis and in the stimulation of acute-phase proteins. 171 Mar 95

Mechanisms of nutrient alteration of hepatic protein synthesis during sepsis are unclear. In vitro, arginine downregulates endotoxin-stimulated hepatocyte protein synthesis but in vivo effects are unknown. This study evaluated the effects of supplemental arginine or glycine on fibrinogen (acute-phase protein), histone, albumin, and liver protein synthesis after Gram-negative sepsis in the rat. Adult rats (225 g, n = 36) were randomized to receive isonitrogenous isocaloric total parenteral nutrition supplemented with 264 mg of N per kilogram per day as either arginine or glycine. On day 5, each group was further randomized to control or sepsis. Sepsis was induced by injection of 8 x 10(7) Escherichia coli per 100 g body weight, and then a continuous infusion of [1-14C]leucine was started. The rats were sacrificed 4 hours later. The fractional protein synthesis rates (percent per day) of histone, fibrinogen, albumin, and liver were determined. Supplemental arginine led to significantly increased histone (p less than 0.05, analysis of variance) and fibrinogen (p less than 0.01, analysis of variance) synthesis in the septic rats compared with all other groups. Histone and albumin synthesis were also significantly increased (p less than 0.05) in the arginine-supplemented control group compared with the glycine-supplemented control group. Arginine supplementation during sepsis significantly increased (p less than 0.05) albumin and liver protein synthesis compared with controls. Histones which are involved in DNA synthesis and are rich in arginine may play a role in the host response to stress and sepsis. These in vivo results appear to contradict hepatocyte-Kupffer cell coculture studies perhaps because of the hormonal and cytokine responses to nutrient substrate and acute septicemia.
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PMID:Harry M. Vars Research Award. Arginine supplementation improves histone and acute-phase protein synthesis during gram-negative sepsis in the rat. 171 54

The clearance rate of endogenous and exogenous circulating lipids during the septic or inflammatory state remains a controversial subject. Thus, we have developed rat models of gram-negative and gram-positive sepsis and of sterile inflammation to study this problem. In addition to the febrile response, these stresses induced some of the following metabolic changes in the blood: decreased total protein, albumin, and ketone body levels and increased lactate, pyruvate, alanine, cholesterol, and triacylglycerol levels. The activities of heart, diaphragm, and adipose tissue lipoprotein lipase and of hepatic lipase decreased to differing extents depending on whether the enzyme substrate was a long-chain or a medium- and long-chain triglyceride-based emulsion. However, the latter emulsion was always hydrolyzed faster than the former. This observation suggests that, during infection/inflammation, the medium- and long-chain triglyceride-based emulsion would be cleared more quickly, would induce less hypertriglyceridemia, and would thus deliver lipid energy more rapidly than a traditional long-chain triglyceride-based emulsion.
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PMID:Decreased lipolytic activity in tissues during infectious and inflammatory stress. 180 2

Prospective evaluation were made of 45 patients with postoperative small bowel fistulas treated with total parenteral nutrition (TPN) and enteral nutrition (EN) between 1971-1988. The administration of TPN in the early treatment of enteric fistulas decreased the mean fistula output significantly (p < 0.05-0.001) and provided an effective tool in the control of high-output fistulas. The electrolyte contents of different fistula secretions were unchanged and the losses through the fistulas depended on the daily output. In patients with high-output fistulas acid-base balance disturbances had to be corrected. When comparing two parenteral nutrition regimens (carbohydrate+amino acids /CH + AA/ versus carbohydrate + amino acids + fat /CH + AA + F/) both facilitated the reduction of fistula secretion (in high-output fistulas. CH + AA = -50.2%; CH + AA + F = -49%). Positive nitrogen balance was achieved in non septic patients after 13 days of treatment. Improvement of serum protein and albumin occurred by the time of fistula healing. In non surviving patients significant decrease in protein synthesis was observed. Out 7 of 75 central venous catheters yielded positive bacterial cultures (9.3%). In 5 patients autopsy proved generalized sepsis. The use of parenteral and enteral nutrition proved to be a powerful method for controlling the enterocutaneous fistulas and maintaining the nutritional integrity of patients.
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PMID:Parenteral and enteral nutrition and the enterocutaneous fistula treatment. I. Investigations on fistula output, nutritional status complications. 184 21

We examined effects of early post-treatment with the methylxanthine pentoxifylline (PTXF), or the cell-permeable adenosine 3', 5'-cyclic monophosphate (cAMP) analog dibutyryl cAMP (db-cAMP) on Escherichia-coli-induced acute lung injury in guinea pigs. Acute lung injury was assessed by measurements of lung water (lung wet/dry weight ratio; W/D ratio), the concentration ratio of 125I-albumin in bronchoalveolar lavage (BAL) fluid and lung tissue compared with plasma (albumin index; BAL-AI or tissue-AI), and total differential leukocyte count in BAL fluid. Mean arterial pressure (Pa) and peripheral WBC counts were monitored continuously over the 8-h experiment. Septicemia was induced by a bolus injection of 2 x 10(9)/kg live E. coli. Thirty minutes later the animals received a bolus injection followed by continuous infusion of PTXF (20 mg/kg + 20 mg/kg/h; n = 8) or db-cAMP (2 mg/kg + 2 mg/kg/h; n = 8) or saline (septic control; n = 8). Nonseptic control groups were also studied. The lung W/D ratio, BAL-AI, lung tissue-AI, and BAL leukocyte count increased significantly in the septic control group. The PTXF-septic and db-cAMP-septic groups showed no significant increase in lung W/D ratio, BAL-AI, and lung tissue-AI. However, there was no difference in BAL total and differential leukocyte count as compared with the septic control group. PTXF and db-cAMP had no effect on E. coli-induced changes in peripheral WBC count and Pa. Comparison in vitro experiments demonstrated that PTXF and db-cAMP inhibited the endotoxin-induced (E. coli) chemiluminescent response of isolated guinea-pig polymorphonuclear leukocytes (PMN).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early post-treatment with pentoxifylline or dibutyryl cAMP attenuates Escherichia coli-induced acute lung injury in guinea pigs. 184 27

Patients treated with high doses of interleukin-2 (IL-2) because of cancer, develop hemodynamic and vasopermeability changes, that resemble those observed in sepsis. These patients thus provide a unique opportunity to study the early events in the development of septic shock. We analysed the changes that occurred in the contact system of coagulation in plasma from 4 patients, who together received seven 12-day cycles of high doses of IL-2. Levels of factor XII and prekallikrein during the cycles progressively fell to 50 and 30% of their initial levels, respectively, whereas significant increases in plasma factor XIIa- and kallikrein-C1-inhibitor complexes were not observed (in 3 out of 211 samples slightly increased levels of both complexes were found). The reductions in factor XII and prekallikrein were only in part due to protein leakage, since levels were still significantly lower, i.e., 80 and 50%, respectively, when corrected for albumin decreases. Levels of high molecular weight kininogen (HMWK) also decreased during IL-2 therapy, however, this decrease paralleled that of albumin. SDS-PAGE analysis of plasma HMWK did not reveal increased cleavage of this protein. The reduction of factor XII and prekallikrein, corrected for protein leakage, significantly correlated with albumin levels and inversely with daily cumulative weight gain in the patients. Thus, we demonstrate that factor XII and prekallikrein decrease during IL-2 therapy. As these decreases, already observed after 1 day treatment, were disproportional to that of albumin, a negative acute phase reactant, and correlated with signs of the vascular leak syndrome, we favor the explanation that they reflected activation rather than a decreased synthesis of the contact system proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies on the contact system of coagulation during therapy with high doses of recombinant IL-2: implications for septic shock. 187 10

This study was designed to test the hypothesis that administration of immune globulin to human neonates with early-onset bacterial sepsis would (1) facilitate neutrophil egress from the marrow, (2) improve serum opsonic capacity, and (3) facilitate recovery from the infectious illness. Twenty-two newborn infants with clinical signs of early-onset sepsis were given an intravenous infusion of either 750 mg of immune globulin (IVIG) per kilogram of body weight or the same volume of a vehicle control (albumin). All 22 infants survived, but significant hematologic, immunologic, and respiratory differences were observed after the IVIG and not after the control infusion. Eleven of the patients had neutropenia; 24 hours after the infusions, the neutropenia had resolved in all six IVIG recipients but persisted in all five control recipients (p less than 0.001). Ten patients had I/T neutrophil ratios (a measure of immature neutrophils to total neutrophils on the leukocyte differential count) of less than 0.2. One hour after completion of the infusions, all five IVIG recipients had elevated I/T ratios (mean +/- SEM:0.10 +/- 0.05 before vs 0.43 +/- 0.03 after infusion; p less than 0.001), suggesting a prompt release of neutrophils from the marrow neutrophil storage pool into the circulation; no increase in the I/T ratio was observed in the control recipients. Six hours after the IVIG infusions, the ratio of arterial oxygen tension to fraction of inspired oxygen increased; no increase was observed after control infusions. Serum concentrations of IgG, IgG1, IgG2, IgG3, IgG4, and total hemolytic complement and the capacity of serum to support opsonophagocytosis of type II and type III group B streptococci increased markedly in the IVIG recipients but not in the control subjects. We conclude that administration of 750 mg IVIG per kilogram to neonates with clinical signs of early-onset sepsis was associated with immunologic, hematologic, and physiologic improvement.
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PMID:Effect on neutrophil kinetics and serum opsonic capacity of intravenous administration of immune globulin to neonates with clinical signs of early-onset sepsis. 190 Oct 82


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