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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peroxynitrite (ONOO-), the reaction product of superoxide (O2-) and nitric oxide (NO), may be a major cytotoxic agent produced during inflammation, sepsis, and ischemia/reperfusion. Bovine Cu,Zn superoxide dismutase reacted with peroxynitrite to form a stable yellow protein-bound adduct identified as nitrotyrosine. The uv-visible spectrum of the peroxynitrite-modified superoxide dismutase was highly pH dependent, exhibiting a peak at 438 nm at alkaline pH that shifts to 356 nm at acidic pH. An equivalent uv-visible spectrum was obtained by Cu,Zn superoxide dismutase treated with tetranitromethane. The Raman spectrum of authentic nitrotyrosine was contained in the spectrum of peroxynitrite-modified Cu,Zn superoxide dismutase. The reaction was specific for peroxynitrite because no significant amounts of nitrotyrosine were formed with nitric oxide (NO), nitrogen dioxide (NO2), nitrite (NO2-), or nitrate (NO3-). Removal of the copper from the Cu,Zn superoxide dismutase prevented formation of nitrotyrosine by peroxynitrite. The mechanism appears to involve peroxynitrite initially reacting with the active site copper to form an intermediate with the reactivity of nitronium ion (NO2+), which then nitrates tyrosine on a second molecule of superoxide dismutase. In the absence of exogenous phenolics, the rate of nitration of tyrosine followed second-order kinetics with respect to Cu,Zn superoxide dismutase concentration, proceeding at a rate of 1.0 +/- 0.1 M-1.s-1. Peroxynitrite-mediated nitration of tyrosine was also observed with the Mn and Fe superoxide dismutases as well as other copper-containing proteins.
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PMID:Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. 141 74

The mediators responsible for maintenance of the hyperdynamic state and the low systemic vascular resistance (SVR) observed in sepsis have not been elucidated. Nitric oxide (.N = O) is a mediator with numerous functions, including regulation of vascular tone and a role in macrophage-mediated cytostasis and microbiostasis. Thirty-nine critically ill trauma and septic patients were studied to determine the relationship between .N = O production and the hyperdynamic state. high plasma levels of NO2-/NO3- (the stable end products of .N = O) were observed in septic patients (p less than 0.02). Low SVR and high endotoxin levels were associated with high NO2-/NO3- values (p = 0.029, p = 0.002). Changes in .N = O levels may mediate the vasodilation seen in sepsis. Low NO2-/NO3- levels were observed in trauma patients (p less than 0.001) and remained low even in the presence of sepsis (p = 0.001).
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PMID:Nitrogen oxide levels in patients after trauma and during sepsis. 195 16

To improve the past statistics of high mortality and morbidity in patients with TEN, definitive measures are required. Early referral and transfer to a burn center and withholding or withdrawing steroid therapy are two crucial factors. Therapeutic goals must be directed toward promotion of wound healing; correction of fluid and electrolyte abnormalities; provision of pulmonary care; prevention or correction of thermal disturbances; control of pain; prevention of physiologic and psychologic disabilities, which may hamper the return to activities of daily living; and above all, prevention of sepsis through protective isolation and refraining from use of invasive lines and catheters. Wound healing is best supported through gentle cleansing with physiologic saline; application of biologic or synthetic skin dressings or silver nitrate dressings; hourly eye care; nutritional support; and avoidance of infection or further injury of the dermis. Collaboration and teamwork by all health care providers are essential, and the quality of intensive nursing care makes the critical difference.
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PMID:Toxic epidermal necrolysis. 205 30

Nitric oxide (NO.) is a short-lived intermediate in a biochemical pathway where L-arginine is converted to L-citrulline and nitrite/nitrate (NO2-/NO3-). This highly reactive molecule is the biologically active component of this inducible pathway in macrophages. Using a rat Kupffer cell:hepatocyte (KC:HC) coculture model, we have previously shown that this combination of cells produces large quantities of both citrulline and NO2-/NO3- if exposed to lipopolysaccharides (LPS) but we did not determine whether nitric oxide was produced or released. We had also shown that this L-arginine metabolism was associated with a profound decrease in total protein synthesis. In these experiments, we show that KC:HC cocultures release nitric oxide into the culture supernatant if exposed to LPS. NO. production by these cells requires L-arginine and is inhibited by NG-mono-methyl-L-arginine. In addition, the time course for NO. release by KC:HC cocultures parallels the previously reported time course for NO2-/NO3- synthesis and the decrease in protein synthesis, supporting the hypothesis that NO. is the reactive nitrogen intermediate of the pathway responsible for this inhibition of protein synthesis. Finally, we show that KC:HC cocultures release more NO. than KC alone in response to LPS, and we propose that the combination of KC and HC acts as a functional unit capable of generating large amounts of NO. from L-arginine in gram-negative sepsis.
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PMID:Kupffer cell:hepatocyte cocultures release nitric oxide in response to bacterial endotoxin. 218 13

Infections in burn patients continue to be the primary source of morbidity and mortality. Topical antimicrobial therapy remains the single most important component of wound care in hospitalised burn patients. The goal of prophylactic topical antimicrobial therapy is to control microbial colonisation and prevent burn wound infection. In selected clinical circumstances topical agents may be used to treat incipient or early burn wound infections. At the present time silver sulfadiazine is the most frequently used topical prophylactic agent; it is relatively inexpensive, easy to apply, well tolerated by patients, and has good activity against most burn pathogens. In patients with large burns the addition of cerium nitrate to silver sulfadiazine may improve bacterial control. Mafenide acetate has superior eschar-penetrating characteristics, making it the agent of choice for early treatment of burn wound sepsis. However, the duration and area of mafenide application must be limited because of systemic toxicity associated with prolonged or extensive use. Other agents, such as nitrofurazone or chlorhexidine preparations, may be useful in isolated clinical situations. The undesirable side effects of silver nitrate solution limit its use by most clinicians at the present time.
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PMID:Current treatment recommendations for topical burn therapy. 222 20

The hepatic failure associated with severe sepsis is characterized by specific, progressive, and often irreversible defects in hepatocellular metabolism (1). Although the etiologic microbe can often be identified, the direct causes and mechanisms of the hepatocellular dysfunction are poorly understood. We have hypothesized that Kupffer cells (KC), which interact with ambient septic stimuli, respond by providing signals to adjacent hepatocytes (HC) in sepsis . Furthermore, we have provided evidence (2, 3) that KC activated by LPS from Gram-negative bacteria can induce profound changes in the function of neighboring HC in coculture. In our model, coculture of either KC (2) or peritoneal macrophages (Mphi)(3) with HC normally promotes HC protein synthesis ([(3)H]leucine incorporation). The addition of LPS or killed Escherichia colt' to such cocultures induces a profound decrease in HC protein synthesis, as well as qualitative changes ([(35)S]methionine, SDS-gel electrophoresis) in protein synthesis without inducing HC death (2, 3) . In this report we show that the inhibition in protein synthesis is mediated via an L-arginine-dependent mechanism. The metabolism of L-arginine by activated Mphi to substances with cytostatic and even lethal effects on target cells is a relatively recent discovery. After the description by Stuehr and Marletta (4, 5) that LPS- triggered Mphi produced nitrite/nitrate (NO(2)(-)/NO(3)(-)), Hibbs et al. (6, 7) and Iyengar et al. (8) demonstrated that L-arginine was the substrate for the formation of both these nitrogen end products and citrulline. A role for the arginine-dependent mechanism in Mphi tumor cytotoxicity (6, 7) and microbiostatic activity (9) has been suggested. However, the in vivo functions of this novel Mphi mechanism have not yet been defined, but it is possible that there are both physiologic as well as pathologic roles. Our in vitro results raise the possibility that some metabolic responses to microbial invasion maybe partially mediated by the L-arginine-dependent mechanism. What other metabolic responses are affected and the possible pathologic consequences remain to be studied.
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PMID:An L-arginine-dependent mechanism mediates Kupffer cell inhibition of hepatocyte protein synthesis in vitro. 292 30

During the 10-year period July 1977 to June 1987, 23 patients were referred to one surgical department with hepatic hydatid cysts. Accurate diagnosis in all but one case was possible by hydatid serology (hydatid immunoelectrophoresis and enzyme-linked immunosorbent assay), and ultrasonography or computed tomography which showed the presence of daughter cysts. Endoscopic retrograde cholangiography demonstrated the presence of hepatic-duct hydatid cysts in one case. The probable source of the hydatid infection was identified in all 23 cases. The surgical management was standardized and included the use of a suction cone to prevent spillage; the closure of biliary communications under vision; 0.5% silver nitrate solution as the scolicidal agent; primary closure of the residual cavity without drainage; omentoplasty for infected cysts; and bile-duct exploration and operative choledochoscopy for choledochal hydatid cysts. Two hepatic wedge resections were performed for hydatid cysts in a Riedel's lobe, but formal liver resection, in which normal liver tissue was sacrificed, was not necessary. There was no mortality and there were no postsurgical hepatobiliary complications such as biliary fistulas, biliary sepsis or jaundice. Three (13%) recurrences were recognized; all three recurrences occurred about five years after the removal of hydatid cysts with numerous daughter cysts, which were located in multiple cavities in both lobes of the liver. Postsurgical surveillance for several years by annual clinical review, hydatid immunoelectrophoresis testing and ultrasonography is recommended.
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PMID:Current management of liver hydatid cysts: results of a 10-year study. 329 Jun 33

A retrospective chart review was conducted of 5418 culture and sensitivity reports from 93 paediatric burn patients to determine profiles of wound flora and invasive organisms, trend analysis and patterns of antibiotic resistance. Coagulase-positive Staphylococcus was the predominant burn wound pathogenic isolate and the predominant invasive organism for burns less than 60 per cent BSA. Pseudomonads were the predominant invasive organism for burn wounds greater than or equal to 60 per cent BSA. Only 7 per cent of all pathogenic isolates were fungi. A significant association was demonstrated between increasing burn size and an increasing incidence of Gram-negative and invasive organisms. Silver sulphadiazine remains a very effective topical agent for the control of bacterial and fungal growth in burn wounds after 10 years of intensive use in this burn unit. Pseudomonad isolates were routinely multi-drug resistant. Pseudomonad isolates from wounds treated topically with a silver sulphadiazine-cerium nitrate mixture were frequently resistant to aminoglycosides, colistin and carbenicillin. It is concluded from this review that severe restrictions on antibiotic usage within burn units, and strict internal environmental control within burn units may help to decrease the incidence of nosocomial resistant strains and cross infection. Regular monitoring of burn wound flora, and the protocol for wound care used in treating these patients have been effective in preventing septic episodes and death due to sepsis.
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PMID:An epidemiological profile and trend analysis of wound flora in burned children: 7 years' experience. 639 10

In a prospective, randomized study of patients with major burns, the efficacy of cerium nitrate-silver sulfadiazine cream was compared with that of silver sulfadiazine cream alone. Sixty patients were studied, in two groups, with matching mean ages and mean burns sizes. Patients with associated injuries, smoke inhalation, or major medical illnesses were excluded from the study. The total number of deaths and the total number of deaths from sepsis were equal in both groups. The total number of patients whose quantitative burns wound biopsies indicated light (10(2) to 10(5) organisms/gm) or heavy (over 10(5) organisms/gm) colonization by microorganisms was not statistically different between the two groups. The distribution of bacterial isolates by organism was similar in both groups. In vitro sensitivity determinations indicated a comparable efficacy between the two agents. In this study no clear-cut superiority of one topical agent over the other could be demonstrated.
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PMID:Cerium nitrate-silver sulfadiazine cream in the treatment of burns: a prospective evaluation. 743 6

Nitric oxide (NO) has been proposed as a mediator of hypotension in septic shock. The aim of this study was to determine whether an inhibitor of NO production, NG-monomethyl-L-arginine (L-NMMA), was able to protect against death in two murine models of experimental gram-negative sepsis. L-NMMA (3-300 mg kg-1) did not improve survival in intravenous or intraperitoneal models of sepsis. Seven h after intravenous infection, L-NMMA (100 mg/kg-1) reduced serum nitrite plus nitrate levels (NO breakdown products) from 774 microM in control-treated animals to 282 microM in L-NMMA-treated animals (P < .001). This compared to a level of 103 microM in uninfected mice. L-NMMA produced little change in bacterial load following infection and did not increase hepatic damage, as measured by serum levels of ornithine carbamoyltransferase. Thus, while L-NMMA may reverse the hyporesponsiveness of peripheral circulation in sepsis, it was unable to prevent death in these models of gram-negative septic shock.
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PMID:Inhibition of nitric oxide synthase in experimental gram-negative sepsis. 750 68


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