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

Enteral nutrition (EN) has several advantages over parenteral nutrition (PN) for postoperative/posttrauma patients. Modern technologies for tube-feeding have made early EN possible. Jejunal tube-feeding has advantages over gastric tube-feeding: faster metabolic recovery, less vomiting, and less risk of regurgitation and aspiration. Immediate or early EN stimulates the splanchnic and hepatic circulations, improves mucosal blood flow, prevents intramucosal acidosis and permeability disturbances, and eliminates the need for stress ulcer prophylaxis. Saliva containing important antimicrobial substances and gastric acidity are important in sepsis prevention. Chewing, saliva, and gastric acidity support gastric nitric oxide (NO) release, important for mucosal blood flow, gastrointestinal (GI) motility, mucus formation, and bacteriostasis. An oral supply of NO-donating substances and chewing of nitrate-rich food, such as lettuce or spinach, can be useful. Oral and mucosa-protective lipids are recommended. H2 blockers and saliva-inhibiting drugs are avoided. Immediate EN should be given, starting with 25 ml/hr and increasing to 100 ml/hr over 24 to 48 hours. For the immunocompromised patient special attention should be given to the purity of water. Bottled water can contain bacteria such as Pseudomonas. Food antioxidants such as glutathione, vitamin E, and beta-carotenes are important. Ingredients for the colonic mucosa are important. Approximately 10% of caloric need is satisfied by so-called colonic food (prebiotics), fermented at the level of the colonic mucosa to produce colonic mucosa nutrients and to prevent gut origin sepsis. More than 10 g of fiber per day is recommended. The fermenting flora (probiotic flora) is deranged owing to disease or antibiotic treatment, and resupply of flora is important. A new concept of ecoimmune nutrition is presented for enteral supply of mucosa-reconditioning ingredients: new surfactants, pseudomucus, fiber, amino acids such as arginine, and mucosa-adhering Lactobacillus plantarum 299.
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PMID:Nutritional support to prevent and treat multiple organ failure. 866 38

1. The cardiovascular failure in sepsis may result from increased nitric oxide biosynthesis, through the diffuse expression of an inducible nitric oxide synthase. In such conditions, nitric oxide synthase inhibitors might be of therapeutic value, but detrimental side effects have been reported with their use, possibly related to the blockade of constitutive nitric oxide synthase. Therefore, the use of selective inhibitors of inducible nitric oxide synthase might be more suitable. The aim of this study was to evaluate the effects of L-canavanine, a potentially selective inhibitor of inducible nitric oxide synthase, in an animal model of septic shock. 2. Anaesthetized rats were challenged with 10 mg/kg lipopolysaccharide intravenously. One hour later, they randomly received a 5 h infusion of either L-canavanine (20 mg h-1 kg-1, n = 15), nitro-L-arginine methyl ester (5 mg h-1 kg-1, n = 13) or 0.9% NaCl (2 ml h-1 kg-1, n = 21). Lipopolysaccharide induced a progressive fall in blood pressure and cardiac index, accompanied by a significant lactic acidosis and a marked rise in plasma nitrate. All these changes were significantly attenuated by L-canavanine, which also improved the tolerance of endotoxaemic animals to acute episodes of hypovolaemia. In addition, L-canavanine significantly increased survival of mice challenged with a lethal dose of lipopolysaccharide. In contrast to L-canavanine, nitro-L-arginine methyl ester increased blood pressure at the expense of a severe fall in cardiac index, while largely enhancing lactic acidosis. This agent did not improve survival of endotoxaemic mice. In additional experiments, we found that the pressor effect of L-canavanine in advanced endotoxaemia (4 h) was reversed by L-arginine, confirming that it was related to nitric oxide synthase inhibition. In contrast, L-canavanine did not exert any influence on blood pressure in the very early stage (first hour) of endotoxaemia or in the absence of lipopolysaccharide exposure, indicating a lack of constitutive nitric oxide synthase inhibition by this agent. 3. In conclusion, L-canavanine produced beneficial haemodynamic and metabolic effects and improved survival in rodent endotoxic shock. The actions of L-canavanine were associated with a selective inhibition of inducible nitric oxide synthase and were in marked contrast to the deleterious consequences of nitro-L-arginine methyl ester, a non-selective nitric oxide synthase inhibitor, in similar conditions.
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PMID:Beneficial effects of L-canavanine, a selective inhibitor of inducible nitric oxide synthase, during rodent endotoxaemia. 866 74

We measured serum concentrations of nitrite/nitrate (NOX), type II phospholipase A2 (PLA2), leukotriene B4 (LTB4), and platelet-activating factor (PAF) in patients with sepsis. These findings were compared between patients with and without septic shock. Serum concentrations of NOX, type II PLA2, LTB4, and PAF acetylhydrolase (PAF-AH) were significantly higher in the group with septic shock (P < 0.0001; P = 0.0060; P = 0.0052; P = 0.0052), indicating the severity of the disease. There were significant correlations between the serum NOX level and serum levels of type II PLA2, LTB4, and PAF-AH (r = 0.6890, P < 0.0001; r = 0.3755, P = 0.0409; r = 0.5095, P = 0.0040, respectively). It is speculated that LTB4 and PAF, both produced with type II PLA2, interact with each other and are involved in the deterioration of pathologic features associated with sepsis. Furthermore, nitric oxide (NO) and eicosanoids interact to play an important role in vascular dilatation during septic shock.
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PMID:Nitrite/nitrate (NOX) and type II phospholipase A2, leukotriene B4, and platelet-activating factor levels in patients with septic shock. 877 66

We assessed the plasma levels of nitrite/nitrate (NOx) and soluble Fas antigen (sFas) in patients with multiple organ failure (MOF). The NOx levels showed high levels in MOF patients with sepsis and without infection. A significant difference was not seen between the MOF patients complicated by sepsis and uncomplicated by infection, although the NOx levels in the former group tended to be higher. There was a significant correlation between NOx levels and sFas levels in MOF patients. Both sFas and NOx levels were high during MOF, and rapidly decreased when MOF was relieved. These findings suggest that sFas and NOx contribute to the development of MOF.
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PMID:Nitrite/nitrate (NOx) and sFas antigen levels in patients with multiple organ failure. 877 78

Three different isoforms of the enzyme nitric oxide synthase (NOS) (EC 1.14.13.39) catalyze the formation of nitric oxide (NO) from l-arginine, which is then converted to l-citrulline. NO released by the constitutive isoforms is involved in a variety of physiologic functions, whereas larger amounts of NO released from the inducible isoform (iNOS) are mostly associated with inflammatory processes. Overproduction of NO in these processes including sepsis and autoimmune diseases can have deleterious consequences and pathophysiologic relevance. In this regard investigations of the regulation and function of iNOS to find specific iNOS inhibitors to block unwanted high levels of NO seem of great interest. The present article gives an overview of several methods and techniques employed to study the expression and regulation of the inducible nitric oxide synthase in in vivo and in vitro models of inflammation. The induction of iNOS was detected at different levels of expression and was compared to functional activity of NOS measured as enzyme activity and nitrite/nitrate production, two stable end products of the NO pathway. Differences in vivo and in vitro are compared and discussed.
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PMID:Expression and Detection of Inducible Nitric Oxide Synthase in Experimental Models of Inflammation 881 45

To investigate the involvement of nitrite/nitrate oxide (NOx) in septic shock, and to evaluate the relationships between NOx and cytokines in patients with this disorder, we evaluated 11 patients with septic shock and 12 patients with sepsis unassociated with shock. NOx were measured with an automated system based on the Griess reaction. The plasma concentrations of various cytokines were determined by enzyme-linked immunosorbent assay. Endotoxin was determined by a specific assay after the plasma samples were processed by a perchloric acid method. The mean plasma levels of NOx in the group with shock significantly exceeded those in the group without shock. Significant correlations were observed between the plasma levels of NOx and those of endotoxin, tumor necrosis factor-alpha, and interleukin 8 in both groups. NOx appeared to be involved in the development of septic shock in humans. Endotoxin and cytokines appeared to be involved in the production of NOx.
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PMID:Nitrite/nitrate oxide (NOx) and cytokine levels in patients with septic shock. 882 74

The inducible isoform of nitric oxide synthase (iNOS) is expressed in various organs, including the lung, during systemic endotoxemia. Overproduction of nitric oxide (NO) by iNOS contributes significantly to the vascular failure and end-organ damage in endotoxemia. Using selective pharmacological inhibitors of iNOS, the purpose of this study was to define the role of iNOS in a rat model of endotoxin-induced pulmonary transvascular flux (TVF). Lung TVF was assessed by a method of Evans Blue permeability index (PI). Bacterial lipopolysaccharide (LPS) (15 mg/kg intraperitoneally [IP]) significantly increased pulmonary iNOS activity and serum levels of nitrite/nitrate (NO2/NO3). This was accompanied by a significant elevation of the PI 5 hours after injection. Selective iNOS inhibition with either S-methyl isothiourea (SMT; 5 mg/kg IP) or aminoguanidine (AG; 20 mg/kg IP), administered 2 hours after LPS injection, significantly prevented the increase in PI associated with LPS injection. Similarly, inhibition of the induction of iNOS with dexamethasone (10 mg/kg IP), given 3 hours before LPS, also inhibited the increase in PI. All three treatments significantly prevented the increase in both lung iNOS activity and serum NO2/NO3 associated with endotoxemia. In conclusion, the overproduction of NO generated by iNOS during systemic endotoxemia causes a vascular leak in the lung. Thus, it is speculated that selective inhibition of iNOS may be beneficial in preventing the development of acute respiratory failure in sepsis.
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PMID:Selective inhibition of the inducible isoform of nitric oxide synthase prevents pulmonary transvascular flux during acute endotoxemia. 886 22

This study is aimed to investigate the relationship between plasma concentrations of nitrite and nitrate as a measure of ongoing nitric oxide (NO) production, the vasodilatory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP), endotoxemia and hemodynamic changes in human septic shock. Thirteen patients with septic shock were studied within 6 h after the development of hypotension. Hemodynamic measurements and blood samples were recorded simultaneously at 2-h intervals from study admission. Eighteen normotensive patients with sepsis were included as control group of patients. On study entry, circulating levels of endotoxin did not relate to either CGRP or nitrite and nitrate plasma values. Septic shock patients had significantly higher plasma CGRP, and nitrite and nitrate concentrations, at each of the four time points, than patients with sepsis, as well as both groups of patients compared to normal subjects. No differences were found in plasma SP levels between the two groups of patients. For pooled data from all septic shock patients and measurements (n = 52), both plasma concentrations of CGRP and nitrite and nitrate were inversely correlated, independently from each other, to systemic vascular resistance. On study admission and at 2-h intervals, plasma CGRP concentrations correlated directly with nitrite and nitrate values. Our observations, thus, point to CGRP acting in concert with NO as important mediators responsible for hypotension in human septic shock.
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PMID:Relationship between circulating levels of calcitonin gene-related peptide, nitric oxide metabolites and hemodynamic changes in human septic shock. 888 78

Expression of the inducible isoform of nitric oxide synthase (iNOS) contributes to the hypotension and vascular hyporeactivity in various models of shock induced by bacterial lipopolysaccharide (LPS). However, the role of iNOS in response to shock caused by live bacteria is more controversial. In the present study, we investigated the role of iNOS in a rat model of cecal ligation and puncture (CLP). CLP resulted in increased plasma nitrite/nitrate levels (up to 59 microM at 24 h) and increased pulmonary iNOS activity (up to 71 fmoles/mg/min at 12 h) and caused a significant vascular hyporeactivity at 18 h. The degree of NO production and iNOS induction was approximately 30% of that observed several hours after administration of LPS in the same species, and the degree of vascular hyporeactivity was less than that observed after LPS injection. Selective inhibition of iNOS with mercaptoethylguanidine (MEG) reduced plasma nitrite/nitrate levels, but did not prevent the development of vascular hyporeactivity, and did not improve survival in this model of CLP. Thus, CLP-induced sepsis causes low-level induction of iNOS, but factors other than iNOS are the crucial determinants of the vascular failure and mortality in this model.
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PMID:Low-level expression and limited role for the inducible isoform of nitric oxide synthase in the vascular hyporeactivity and mortality associated with cecal ligation and puncture in the rat. 890 40

Bacterial lipopolysaccharides (LPS) induce the activity of guanosine triphosphate (GTP)-cyclohydrolase I (GTP-CHI), the first enzyme in the biosynthesis of tetrahydrobiopterin (H4bip) from GTP in endothelial cells and macrophages. In these and other cells, LPS also acts costimulatory with cytokines, i.e., mainly tumor necrosis factor-alpha (TNF-alpha). H4bip is the cofactor for nitric oxide synthase (NOS). We were interested in comparing the pteridine and nitrate levels in two baboon models: a hyperdynamic sepsis model and a hemorrhagic traumatic shock model. Our results show a similar response of pteridines (H4bip, neopterin) and nitrite/nitrate levels to an immune stimulus. LPS, which peaks rapidly, induces a sustained increase in pteridine levels in septic animals. Since hemorrhagic animals show very little response in terms of cytokine production, it was not possible to measure the induction of neopterin and nitrite/nitrate. This information could aid our understanding of the regulatory mechanisms in various forms of experimental shock.
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PMID:Pteridine and nitrite/nitrate formation in experimental septic and traumatic shock. 890 41


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