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

Amino asid metabolism was studied by thin layer chromatography in 25 Pasteurella multocida strains isolated from various manifestations of the disease chicken septicemia. Six amino acids were used: DL-ornithin, L-cystein, L-asparagin, DL-serin, L-arginin and Acidum glutaminicum. The Pasteurella strains studied include in their metabolism the amino acid asparagin, but serin and cystein are excluded. The strains isolated from birds suffering from acute and atypical septicemia do not metabolize ornithin, while these isolated from birds having wattles oedema or from calves suffering from arthritis metabolize it. The reaction of Pasteurellae to arginin and glutamic acid varies and no regularity in this respect is observed. Strains isolated from calves suffering from bronchopneumonia do not include in their metabolism any one of the named amino acids. As a result of the test applied a correlation between the Pasteurella multocida biotypes assessed by the authors and the amino acid metabolism was established. This is one proof more that the isolated pasteurellae can be groupped in two big biotypes by the tests for virulence in birds and including in their metabolism the amino acid ornithin.
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PMID:[Amino acid metabolism in Pasteurella multocida studied using thin-layer chromatography]. 741 30

Oxygen radicals and oxygen radial mediators are thought to be important components in the development of acute lung injury, sepsis, and multiple organ failure. Injured patients, patients with pulmonary diseases, and multiple trauma patients also showed an elevated lipid peroxidation, indicating increased oxidant stress. N-Acetylcysteine (NAC) has been used as an antioxidant in a wide variety of experiments. NAC has been suggested to act by raising concentrations of cysteine, and hence glutathione, and by scavenging of oxidant species [1, 11, 17, 29]. The present study was designed to investigate whether the application of NAC in intubated patients has an effect on concentrations of reduced glutathione in plasma and bronchoalveolar lavage fluid (BAL) and on the lipid peroxidation products malondialdehyde and conjugated dienes. Because NAC has been widely used as a mucolytic drug for the treatment of lung diseases, the influence on tracheobronchial mucus was studied, too. METHODS. In a randomized, double-blind, placebo-controlled study, a total of 38 long-term ventilated patients of a surgical intensive care unit were investigated. Patients were treated for 5 days with either 3 g NAC/day or placebo. The plasma concentration of reduced glutathione, malondialdehyde, and conjugated dienes were measured on admission and on the 3rd and 5th days of treatment [8, 34, 48]. Additionally, the numbers of tracheobronchial suctionings were registered and chest radiographs were evaluated. A fibre-bronchoscopy was performed on admission and on the 3rd day of treatment. The amount and viscidity of tracheobronchial secretions were examined semiquantitatively, and glutathione levels were measured in the unconcentrated BAL. The study was approved by the ethics committee of the University of Ulm. RESULTS. The two groups were comparable with respect to age, sex, APACHE II score and diagnosis (Table 1). We found no significant differences in reduced glutathione levels in the plasma or in the BAL (Figs. 1, 2). Plasma concentrations of malondialdehyde were similar (Fig. 3). Only the levels of conjugated dienes were significantly higher on the 5th treatment day in the placebo group (Fig. 4). The organ function of the lung (FiO2, PEEP, PaO2), liver (SGOT, bilirubin), and kidney (creatinine) and coagulation parameters (PTT, prothrombin time, platelet count) were similar in the two groups during the time of investigation. We observed no clinically relevant differences in the tracheobronchial mucus (Table 2). CONCLUSION. The present data do not support routine use of NAC in ventilated patients, either as an antioxidant or as a mucolytic agent. Intravenous administration of 3 g NAC/day had no clinically relevant effect on glutathione levels, lipid peroxidation products, tracheobronchial mucus, and clinical condition.
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PMID:[The application of n-acetylcysteine as an antioxidant and mucolytic in mechanical ventilation in intensive care patients. A prospective, randomized, placebo-controlled, double-blind study]. 748 27

Denutrition is often associated with poor postoperative outcome. However, a large body of evidence, from studies comparing perioperative parenteral (PN) or enteral (EN) nutrition to the absence of perioperative nutrition, suggests that perioperative nutritional support provides significant improvements in both nutritional status and postoperative clinical outcome in selected patients who are or will become malnourished. The aim of this study was to select and review all relevant articles comparing perioperative parenteral and enteral nutritional support, either in terms of clinical outcome, or risks and costs, or in pathophysiological terms. Twelve clinical reports were reviewed. All contained methodological flaws, mainly type II statistical error due to an insufficient number of patients, inaccurate primary diagnosis, absence of blinding, and lack of objective criteria of judgement. These concerns warrant caution in interpreting the results. Moderately strong (grade B) recommendations can only be drawn from these studies: PN (compared to early EN) is associated with a higher rate of sepsis in patients following abdominal trauma; EN is as efficient as PN in patients following surgery; EN is safe and cheaper than PN. PN formulae lack many important nutrients (glutamine, arginine, cysteine, peptides, fibers, n-3 polyunsaturated fatty acids, and nucleotides). Many experimental (animal) and some clinical (in non surgical patients) studies showed that PN (compared to EN) induces gut mucosal atrophy, liver dysfunction, gut bacterial translocation and immune dysfunction. The final aim of PN and EN would therefore strikingly differ. The qualitatively imperfect PN would only supply the fasting patient with quantitative amounts of calories and proteins. Due to initially limited digestive tolerance, EN provides less nutrition than PN does, but would finally lead to the same or even better outcome, due to its ability to counteract stress induced gut and immune dysfunction. Current evidence therefore suggests that early EN is superior to PN in trauma patients, and not different from but cheaper (and therefore more cost-effective) than PN in surgical patients. Further controlled, randomised, and blinded studies including sufficient sizes of groups are required, especially in the surgical setting, to address a large number of still unanswered questions.
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PMID:[Respective indications of enteral or parenteral nutrition during pre- and post-operative periods]. 748 29

The effects of endotoxin on the activities of the major Na(+)-independent amino acid transporters in rat liver (Systems n, asc, L, bo,+, and y+) were studied using using hepatic plasma membrane vesicles (HPMVs). Rats were treated with a single dose of Escherichia coli endotoxin (E. coli lipopolysaccharide 0127:B8 (LPS), 7.5, 15, or 30 mg/kg BW) and HPMVs were prepared by Percoll density gradient centrifugation at various timepoints after LPS administration. Vesicle purity and integrity was established by assay of enzyme markers and identical equilibrium uptakes. The activities of the Na(+)-independent amino acid transport systems y+ and bo,+ (arginine), asc (alanine and cysteine), L (leucine), and n (glutamine) were evaluated by measuring the uptake of radiolabeled amino acids using a rapid mixing/filtration technique. Amino acid uptake by HPMVs consisted of saturable and nonsaturable components. Prior treatment with endotoxin did not alter the activities of Systems n, asc, or L but resulted in a time- and dose-dependent stimulation of saturable arginine transport. Arginine transport increased within 2 h of LPS administration and exhibited a return towards basal levels by 24 h. Nonsaturable uptake (diffusion) in HPMVs was unaltered by LPS treatment. Kinetic analysis of arginine transport demonstrated the presence of both a high affinity and a low affinity carrier. Treatment with LPS resulted in a 73% increase in the Vmax of the high affinity carrier (System y+) and a 25% increase in the Vmax of the low affinity transporter (System bo,+). The data indicate selective stimulation of Na(+)-independent arginine transport in the liver during endotoxemia which may serve to support important arginine-dependent pathways during sepsis.
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PMID:Hepatic Na(+)-independent amino acid transport in endotoxemic rats: evidence for selective stimulation of arginine transport. 774 45

The effect of the antioxidant N-acetyl-L-cysteine was studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture. N-Acetyl-L-cysteine significantly improved survival during the 6 days following sepsis induction and caused lower liver toxicity. This effect was not related to free radicals generated by xanthine oxidase which was significantly induced in liver after cecal ligation and puncture. A specific inhibitor of xanthine oxidase, allopurinol, significantly reduced this enzyme and reduced the early survival rate. The effect of N-acetyl-L-cysteine was not related either to a reduction in tumor necrosis factor production or to a modulation of nitrites or to liver glutathione content. These results show that the induction of xanthine oxidase is not deleterious in this model of sepsis and suggest that N-acetyl-L-cysteine works as a direct antioxidant and scavenger of free radicals generated from other sources.
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PMID:Effect of N-acetyl-L-cysteine on sepsis in mice. 779 76

Nitric oxide reacts with superoxide to form peroxynitrite, a potential mediator of oxidant-induced cellular injury. The endothelium is a primary target of injury in many pathological states, including acute lung injury, sepsis, multiple organ failure syndrome, and atherosclerosis, where enhanced production of nitric oxide and superoxide occurs simultaneously. It was hypothesized that stimulation of endothelial cell nitric oxide production would result in formation of peroxynitrite. Immediate oxidant production was detected by luminol- and lucigenin-enhanced chemiluminescence from cultured bovine aortic endothelial cells exposed to bradykinin or to the calcium ionophore A23187. Luminol-enhanced chemiluminescence was efficiently inhibited by the nitric oxide synthase inhibitor nitro-L-arginine methyl ester and by superoxide dismutase, implying dependence on the presence of both nitric oxide and superoxide for oxidant production. Inhibition of luminol-enhanced chemiluminescence by nitro-L-arginine methyl ester was partially reversed by L-arginine, but not by D-arginine. Cysteine, methionine, and urate, known inhibitors of peroxynitrite-mediated oxidation, inhibited luminol-enhanced chemiluminescence, while the hydroxyl radical scavengers, mannitol and dimethylsulfoxide, and catalase did not. Bicarbonate increased luminol-enhanced chemiluminescence in a concentration-dependent manner. Superoxide production, detected by lucigenin-enhanced chemiluminescence, was slightly increased in the presence of nitro-L-arginine methyl ester, suggesting that endothelial cell-produced superoxide was partially metabolized by reaction with nitric oxide. These results are consistent with agonist-induced peroxynitrite production by endothelial cells and suggests that peroxynitrite may have an important role in oxidant-induced endothelial injury.
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PMID:Agonist-induced peroxynitrite production from endothelial cells. 817 19

Because oxygen free radicals have been implicated in the endothelial cell damage and in the myocardial depression occurring during severe sepsis, we investigated whether N-acetyl-L-cysteine (NAC) could influence the oxygen extraction capabilities during an acute reduction in blood flow induced by cardiac tamponade after endotoxin challenge. Sixteen anesthetized, saline-infused, and ventilated dogs received Escherichia coli endotoxin (2 mg/kg) 30 min before tamponade was induced by repeated bolus injections of warm saline into the pericardial space. Thirty minutes before endotoxin administration, nine dogs received NAC (150 mg/kg, followed by a 20 mg.kg-1.h-1 infusion); the other seven dogs served as a control group. The NAC group maintained higher cardiac index, oxygen delivery (DO2), and left ventricular stroke work index, but lower systemic and pulmonary vascular resistance, than the control group. The oxygen uptake (VO2) levels at critical DO2 (DO2crit) were identical in the two groups. However, DO2crit was significantly lower in the NAC than in the control group (8.1 +/- 1.7 vs. 10.8 +/- 1.8 ml.kg-1.min-1, P < 0.01). Critical oxygen extraction ratio and the slope of the VO2-to-DO2-dependent line were higher in the NAC than in the control group (72 +/- 14 vs. 53 +/- 15% and 0.80 vs. 0.56, respectively; both P < 0.05). The peak lactate and the maximal tumor necrosis factor (TNF) levels were lower in the NAC than in the control group (5.2 +/- 0.4 vs. 7.6 +/- 0.4 mM, and 0.14 +/- 0.03 vs. 1.21 +/- 0.58 ng/ml, respectively; both P < 0.01). NAC significantly increased glutathione peroxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effects of N-acetyl-L-cysteine in endotoxemia. 820 75

Classical galactosaemia, deficiency of galactose-1-phosphate uridyltransferase (GALT), is characterized by acute symptoms of hepatomegaly, jaundice, sepsis, cataracts and growth retardation. Treatment with dietary galactose restriction corrects these complications immediately; however, most of these children develop long-term complications of verbal dyspraxia, mental retardation and ovarian failure. Our previous molecular study showed that the most common mutation of the GALT gene is a missense mutation of Q188R (replacement of glutamine-188 by arginine) in approximately 60-65% of the German galactosaemic population. The coding region of GALT was amplified by the polymerase chain reaction from genomic DNA of classical galactosaemic individuals, who are negative or heterozygous for Q188R, and was further characterized by direct sequencing. Three new disease-causing mutations, two missense and a stop codon mutation, were identified in three patients from two families with mild galactosaemic variants: firstly R67C, replacement of arginine-67 by cysteine and W316X, the stop codon at tryptophan-316 in one male; secondly A330V, replacement of alanine-330 by valine in two female siblings. In the first family the patient was also heterozygous for the polymorphism N314D and in the second family both girls were compound heterozygotes for Q188R and A330V. All three galactosaemic individuals have a considerable amount of the residual GALT activity in RBC and the galactose-1-phosphate (GALP) level decreased much faster on treatment than that of other galactosaemic patients with missense mutations such as Q188R. The clinical and biochemical data of these patients were much more favourable in comparison with those of two female galactosaemic individuals, one homozygous for L195P and the other compound heterozygous for Q188R and L195P. These three missense mutations (R67C, L195P and A330V) also occur in highly conserved regions. These observations suggest that the phenotypic variation in galactosaemic individuals may be due to different molecular aetiologies.
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PMID:Mutations in the galactose-1-phosphate uridyltransferase gene of two families with mild galactosaemia variants. 859 37

Reactive oxygen metabolites (ROMs) are thought to play a key role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Accordingly, the use of ROM scavengers, such as N-acetyl-cysteine or dimethylthiourea, as therapeutic adjuncts to prevent oxidant-mediated damage to the lung have been evaluated extensively in animal models of ARDS. Results with this approach have been quite variable among studies. Another strategy that has been examined in animal models of ARDS is the administration of various enzymes, particularly superoxide dismutase (SOD) or catalase (CAT), in an effort to promote the conversion of ROMs to inactive metabolites. In theory, this strategy should be more effective than the use of ROM scavengers since a single molecule of a catalytically active molecule can neutralize a large number of molecules of a reactive species, whereas most scavengers act in a stoichiometric fashion to neutralize radicals on a mole-for-mole basis. This notion is supported by studies showing that prophylactic treatment with CAT provides impressive protection against acute lung injury induced in experimental animals by the administration of lipopolysaccharide (LPS). Results with SOD have been more variable. Recently, we have utilized a porcine model of LPS-induced ARDS to investigate the therapeutic potential of EUK-8, a novel, synthetic, low molecular salen-manganese complex that exhibits both SOD-like and CAT-like activities in vitro. Using both pre- and post-treatment designs, we have documented that treatment with EUK-8 significantly attenuates many of the features of LPS-induced acute lung injury, including arterial hypoxemia, pulmonary hypertension, decreased dynamic pulmonary compliance, and pulmonary edema. These findings support the view that salen-manganese complexes warrant further evaluation as therapeutic agents for treatment or prevention of sepsis-related ARDS in humans.
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PMID:Role of oxidant stress in the adult respiratory distress syndrome: evaluation of a novel antioxidant strategy in a porcine model of endotoxin-induced acute lung injury. 882 94

Proinflammatory cytokines released by hepatic macrophages (Kupffer cells) have a central role in the pathogenesis of liver injury and the cardiovascular abnormalities of sepsis. Because cytokine release is controlled primarily at the level of gene expression, intracellular signalling mechanisms that control the transcription of cytokine genes are critical links to organ injury. Oxidant stress up-regulates and antioxidants down-regulate the pleiotropic transcription factor NF-kappa B, a DNA-binding protein that induces the expression of cytokines and vascular adhesion molecules. Thiol-bearing molecules are also important inhibitors of NF-kappa B activation, but whether this inhibition represents an antioxidant effect is unknown. This study was undertaken to determine whether important endogenous and pharmacological thiols modulate the activation of NF-kappa B and the release of tumour necrosis factor alpha (TNF-alpha) from Kupffer cells and to ascertain whether these effects are mediated through glutathione. Exposure of rat Kupffer cells to a physiologically relevant concentration of lipopolysaccharide (10 ng/ml) activated NF-kappa B within 1 h and induced the release of TNF-alpha over 5 h. Cellular glutathione content remained unchanged after lipopolysaccharide exposure, but both glutathione monoethyl ester and N-acetyl-L-cysteine increased cellular glutathione levels, blocked NF-kappa B activation and inhibited the release of TNF-alpha. Inhibition of glutathione synthesis prevented the NAC-induced increase in Kupffer cell glutathione, yet it did not prevent the inhibition of TNF-alpha release by NAC. Thus the inhibition of NF-kappa B activation by pharmacological thiols such as NAC might reflect a more general role of the intracellular thiol redox status in NF-kappa B regulation rather than the antioxidant properties of these agents.
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PMID:Thiol regulation of endotoxin-induced release of tumour necrosis factor alpha from isolated rat Kupffer cells. 900 92


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