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)

Lipopolysaccharide is strongly associated with septic shock, leading to multiple organ failure. It can activate monocytes and macrophages to release proinflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and nitric oxide (NO). The present experiments were designed to induce endotoxin shock by an intravenous injection of Klebsiella pneumoniae lipopolysaccharide (LPS, 10 mg/kg) in conscious rats. Arterial pressure and heart rate (HR) were continuously monitored for 48 h after LPS administration. N-Acetylcysteine was used to study its effects on organ damage. Biochemical substances were measured to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-alpha, IL-1 beta, methyl guanidine (MG), and nitrites/nitrates. LPS caused significant increases in blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-1 beta, MG levels, and HR, as well as a decrease in mean arterial pressure and an elevation of nitrites/nitrates. N-Acetylcysteine suppressed the release of TNF-alpha, IL-1 beta, and MG, but enhanced NO production. These actions ameliorate LPS-induced organ damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound in sepsis prevention and treatment.
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PMID:N-acetylcysteine ameliorates lipopolysaccharide-induced organ damage in conscious rats. 1496 65

The high morbidity and mortality of severe sepsis and septic shock fosters a continuous search for novel therapies that go beyond pure correction of oxygenation and hemodynamics. Within this scope, N-acetylcysteine shows great promise. Beside proven anti-oxidant, anti-inflammatory and cytoprotective effects, N-acetylcysteine does also ensure endothelial protection and enhances microvascular blood flow. Studies that put these highly favourable properties to the clinical test remain scarce but are definitely needed to determine whether N-acetylcysteine has a place in our therapeutic armamentarium against sepsis.
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PMID:N-acetylcysteine in clinical sepsis: a difficult marriage. 1531 15

Contrast-induced nephropathy (CIN) is a leading cause of in-hospital acute renal failure in critically ill patients who undergo radiographic procedures. Critical care patients are at particular risk, often because of baseline renal dysfunction, older age, and the presence of diabetes. In addition, there are superimposed risks, including volume depletion, sepsis, and use of nephrotoxic drugs. The rates of CIN (defined as an increase in serum creatinine by >25% or 0.5 mg/dL) can be predicted by using multivariate tools. Prevention measures include adequate hydration, use of N-acetylcysteine and iso-osmolar contrast, and for patients who are at the highest risk, prophylactic hemofiltration.
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PMID:Contrast-induced nephropathy. 1578 Nov 62

Toxic Epidermal Necrolysis (Lyell's syndrome) is a rare but very serious dermatological lesion, characterized by the sudden onset of high fever, signs of systemic toxicity and intense mucocutaneous exfoliation. Its pathophysiology is not yet well determined, although it is almost consensual the presence of an immunological basis. It appears usually as an answer to the taking of a given drug, and, in spite of being self-limited in the absence of complications, if not well managed it is associated with great morbidity and a high mortality, due, in most cases, to the developing of sepsis. Treatment includes mainly the immediate suspension of the inducing drug and the precocious admission of the patient in a hospital facility with the capacity to provide intensive support care and to minimize the infectious risk, having also the conditions for the execution of surgical debridement and covering of the affected areas, that is to say in Burn Units. There are in study several therapeutical measures designed to lower the morbidity and mortality of this syndrome, namely the use of plasmapheresis; the administration of high doses of N-acetylcysteine; immunosuppression; hyperbaric oxygen, etc. The authors present the treatment protocol in use at the Coimbra Burns Unit, in Portugal, illustrated with a clinical case from that Unit.
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PMID:[Toxic Epidermal Necrolysis (Lyell syndrome): a pathology for burn units]. 1592 43

The antioxidant N-acetylcysteine (NAC) prevented sepsis-induced diaphragmatic dysfunction. As an indirect antioxidant NAC was shown to induce superoxide dismutase (SOD) activity in immune cells from endotoxaemic mice. The aim of this study was to assess whether NAC acts as an indirect antioxidant by inducing manganese (Mn)-SOD activity in the diaphragms of endotoxaemic rats, while preventing muscle dysfunction. A controlled study was conducted, in which protein carbonylation, Mn-SOD, catalase, and 3-nitrotyrosine immunoreactivity were detected using immunoblotting and immunohistochemistry in rat diaphragms. Six groups were studied for 24 h after a saline (control) or lipopolysaccharide (LPS; 20 mg.kg-1) i.p. injection in the absence and presence of NAC pre-treatment (either 1.5 or 3 mmol.kg(-1).24 h-1 for 7 days, oral administration). Diaphragm mitochondrial Mn-SOD activity and respiratory muscle function were also determined. Within 24 h, LPS induced maximal inspiratory pressure reduction, increasing diaphragmatic protein carbonylation and nitration. Pre-treatment with 3 mmol.kg-1 NAC clearly increased muscle Mn-SOD protein content and activity in both LPS- and saline-injected animals, while reducing protein carbonylation and nitration, and partially preventing the LPS-induced respiratory muscle dysfunction. Data produced from this study indicate that high doses of N-acetylcysteine induces manganese superoxide dismutase, as well as preserves its activity, possibly by preventing nitration of critical tyrosine residues of the enzyme.
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PMID:N-acetylcysteine increases manganese superoxide dismutase activity in septic rat diaphragms. 1631 32

This study investigates the association of oxidative stress with the function of the phrenic nerve and inquires whether N-acetylcysteine (NAC) may counteract the possible detrimental effects. Thirty rats were divided into three groups: sham, cecal ligation and puncture (CLP), and CLP plus NAC treatment. Sepsis was produced by the CLP procedure. NAC was administered at 70 mg/day for 7 days. Electrophysiology was evaluated by the needle electromyography of the diaphragm and phrenic nerve conduction study. Oxidative stress was evaluated by malondialdehyde (MDA), nitrite/nitrate (NN), and reduced-glutathione (ReGSH) levels and myeloperoxidase (MPO) and catalase (CAT) activities in the phrenic nerve. In the CLP group, ReGSH and CAT were decreased (P = 0.0001, P = 0.07, respectively); and MDA, MPO, and NN were increased (P = 0.02, P = 0.0001, P = 0.043, respectively), compared with the sham group. NAC administration increased the ReGSH (P = 0.036) and decreased the MDA, MPO, and NN (P = 0.008, P = 0.01, P = 0.032, respectively), compared with the CLP group. In the CLP group, electrophysiology revealed reductions in the number of motor unit action potentials (P = 0.0001) and prolongations in the latency of the compound nerve action potential (P = 0.0001), indicating phrenic nerve neuropathy. NAC administration significantly ameliorated these electrophysiological alterations (P = 0.011, P = 0.0001, respectively), compared with the CLP group. The present results showed that intraabdominal sepsis is closely associated with phrenic nerve neuropathy. In addition, NAC administration protects the rats against the detrimental events of sepsis.
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PMID:N-acetylcysteine protects the rats against phrenic nerve dysfunction in sepsis. 1636 83

Sepsis impairs diaphragmatic contractility and endurance capacity and increases diaphragmatic fatigability. Several investigations have shown that administration of a number of free radical scavengers, such as N-acetylcysteine (NAC), protects the diaphragm from the development of endotoxin-mediated diaphragmatic dysfunction. The aim of this study was to evaluate the effects of melatonin (CAS 73-31-4), a naturally occurring potent antioxidant, on diaphragmatic contractility and lipid peroxidation as a marker of oxidative stress in endotoxemic rats. Rats were randomly divided into four groups: control group, endotoxemic group, melatonin group and endotoxemic plus melatonin group. Melatonin was administered by intraperitoneal injection 30 min before endotoxin inoculation to animals. Diaphragmatic function and malondialdehyde (MDA) level analysis as an indicator of lipid peroxidation were assessed 17 h after endotoxin or saline inoculation. Endotoxemia decreased the development of diaphragm fatigue and diaphragmatic MDA levels. The effects of endotoxemia on diaphragmatic contractions and fatigability were reversed and returned to control levels by melatonin administration. However, melatonin did not prevent the increase in muscle MDA content. In conclusion, the present study demonstrated that melatonin attenuated the endotoxin-induced impairment of diaphragm function. This effect of melatonin does not seem to be related to its antioxidant properties.
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PMID:Beneficial effects of melatonin on diaphragmatic contractility and fatigability in Escherichia coli endotoxemic rats. 1657 23

The adequacy range of dietary requirements of specific amino acids in disease states is difficult to determine. In health, several techniques are available allowing rather precise quantification of requirements based on growth of the organism, rises in plasma concentration, or increases in the oxidation of marker amino acids during incremental administration of the amino acid under study. Requirements may not be similar in disease with regard to protein synthesis or with regard to specific functions such as scavenging of reactive oxygen species by compounds including glutathione. Requirements for this purpose can be assessed only when such a function can be measured and related to clinical outcome. There is apparent consensus concerning normal sulfur amino acid (SAA) requirements. WHO recommendations amount to 13 mg/kg per 24 h in healthy adults. This amount is roughly doubled in artificial nutrition regimens. In disease or after trauma, requirements may be altered for methionine, cysteine, and taurine. Although in specific cases of congenital enzyme deficiency, prematurity, or diminished liver function, hypermethionemia or hyperhomocysteinemia may occur, SAA supplementation can be considered safe in amounts exceeding 2-3 times the minimal recommended daily intake. Apart from some very specific indications (e.g., acetaminophen poisoning), the usefulness of SAA supplementation is not yet established. There is a growing body of data pointing out the potential importance of oxidative stress and resulting changes in redox state in numerous diseases including sepsis, chronic inflammation, cancer, AIDS/HIV, and aging. These observations warrant continued attention for the potential role of SAA supplementation. In particular, N-acetylcysteine remains promising for these conditions.
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PMID:Adequate range for sulfur-containing amino acids and biomarkers for their excess: lessons from enteral and parenteral nutrition. 1670 41

N-acetylcysteine (NAC) is an antioxidant and cytoprotective agent with scavenging action against reactive oxygen species and inhibitory effects on pro-inflammatory cytokines. In a previous study, we found that pretreatment with NAC attenuated organ dysfunction and damage, reduced the production of free radicals, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) following endotoxemia elicited by administration of lipopolysaccharide (LPS). In the present study, we tested the effects of post-treatment with NAC on the sepsis-induced change. Post-treatment imitates clinical therapeutic regimen with administration of drug after endotoxemia. Endotoxin shock was induced by intravenous injection of Klebsiella pneumoniae LPS (10 mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 48 h after LPS administration. NAC was given 20 min after LPS. Measurements of biochemical substances were taken to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-alpha, interleukin-6 (IL-6), and interleukin-10 (IL-10). LPS significantly increased blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-6, IL-10 levels and HR, and decreased MAP. Post-treatment with NAC diminished the decrease in MAP, increased the HR, and decreased the markers of organ injury (BUN, Cre, LDH, CPK, GOT, GPT) and inflammatory biomarkers (TNF-alpha, IL-6, IL-10) after LPS. We conclude that post-treatment with NAC suppresses the release of plasma TNF-alpha, IL-6, and IL-10 in endotoxin shock, and decreases the markers of organ injury. These beneficial effects protect against LPS-induced kidney, heart and liver damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound after sepsis.
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PMID:Post-treatment with N-acetylcysteine ameliorates endotoxin shock-induced organ damage in conscious rats. 1686 Mar 47

Cancer of the esophagus has a poor long-term prognosis and a high peri-operative morbidity in which pulmonary complications play a major role. The combination of the surgical approach, pre-existing pulmonary disorders, poor nutritional status and the release of pro-inflammatory cytokines may be contributing factors. N-acetylcysteine ((NAC) has been shown to have oxygen scavenging abilities. In severe sepsis and acute respiratory distress syndrome, positive effects of NAC on morbidity and mortality were discovered. In this observational study peri-operative high dose NAC was administered in 22 patients. The effects of this treatment on respiratory function, morbidity and survival were studied. These prospectively collected data were compared with data of a matched, retrospective group without NAC treatment. There were no significant differences between the groups in terms of socio-demographic data, preoperative pulmonary function, intra-operative course and oncologic characteristics. The oxygenation indices at the postoperative hours 2 (P = 0.019), 4 (P < 0.001), 8 (P = 0.035), 12 (P = 0.035) and 24 (P = 0.046) were significantly higher in the NAC group. After 36 h, the difference between groups was no longer significant (P = 0.064). NAC-treated patients showed significant lower overall pulmonary morbidity, 45.5% versus 81.8% (P = 0.027). Surgical morbidity, intensive care unit and hospital stay were not significantly different between groups, mortality was zero. Kaplan-Meier curves showed no significant difference in survival 12 months postoperatively. These data indicate that postoperative oxygenation can be improved and rate of overall pulmonary complications is reduced using peri-operative high dose NAC in transthoracic esophagectomy.
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PMID:High dose N-acetylcysteine to prevent pulmonary complications in partial or total transthoracic esophagectomy: results of a prospective observational study. 1776 Jun 53


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