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)

To examine alterations in amino acid metabolism after trauma and sepsis, male Sprague-Dawley rats underwent no operation (control, CON), celiotomy (trauma, TRA), or cecal ligation and puncture (sepsis, CLP). After 16 hr, plasma amino acid concentrations were determined. A second group of similarly prepared animals underwent isolated liver perfusion, and net amino acid uptake or release was determined over 30 min. Sepsis significantly decreased total amino acid concentration in portal plasma (CON, 3486 +/- 156 nmole/ml; TRA, 3407 +/- 150 nmole/ml; CLP, 2738 +/- 148 nmole/ml). Glutamine concentrations were uniformly lower in portal plasma than in arterial plasma in all states. There were depressed concentrations of the branched chain amino acids (BCAA) in portal plasma after trauma but not sepsis. In the isolated liver perfusion model, a marked increase in amino acid uptake was induced by sepsis (CON, 39.9 +/- 7.9 mumol/g liver protein; TRA, 49.5 +/- 17.3 mumol/g liver protein; CLP, 124 +/- 11 mumol/g liver protein). In addition, there was significantly greater uptake of threonine, asparagine, proline, methionine, tyrosine, and arginine. Although the BCAA isoleucine and valine were taken up to a greater extent in sepsis, the overall BCAA uptake was not significantly greater in sepsis than in control (CON 6.92 +/- 2.15 mumol/g liver protein vs CLP 15.8 +/- 1.9 mumol/g liver protein). The greatest increase in uptake following sepsis was among the gluconeogenic precursor amino acids alanine, glycine, threonine, and serine (CON, 27.0 +/- 4.2 mumol/g liver protein, TRA, 38.8 +/- 8.9 mumol/g liver protein; CLP, 62.8 +/- 6.0 mumol/g liver protein).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amino acid uptake in isolated, perfused liver: effect of trauma and sepsis. 339 92

To evaluate the role of nitric oxide (NO) in the attenuated vascular reactivity observed in sepsis, we utilized the specific NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Male Sprague-Dawley rats (n = 16) were randomized to either sepsis induced by cecal ligation and perforation (CLP; n = 8) or sham procedure (Sham; n = 8). Vascular reactivity was assessed by measuring the pulmonary pressor response to hypoxia (HPV) (fractional inspired O2 concentration = 0.08) and the pulmonary and systemic pressor response to an intravenous infusion of phenylephrine (1.5-6.0 micrograms.kg-1.min-1). Twenty-four hours after surgery, CLP animals had significantly attenuated HPV compared with Sham animals. In response to hypoxia the change in total pulmonary vascular resistance during hypoxia was 0.008 +/- 0.004 and 0.021 +/- 0.006 mmHg.min-ml-1 in CLP and Sham animals, respectively (P < 0.05). The pulmonary and systemic blood pressure response to phenylephrine was also attenuated in CLP compared with Sham animals. After L-NAME infusion (15 mg/kg), there was a significant augmentation of the HPV response in Sham animals. In contrast, the HPV response in CLP animals was unchanged after L-NAME. The attenuated pressor response to phenylephrine in neither the pulmonary nor the systemic circulation was changed after the administration of L-NAME. These data suggest that in rats, excess NO is not an important mediator of the attenuated vascular reactivity observed in sepsis.
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PMID:Effect of inhibition of NO synthase on vascular reactivity in a rat model of hyperdynamic sepsis. 752 65

Patients with sepsis often require anaesthesia for surgical procedures. Anaesthesia can be unpredictable and the most haemodynamically stable agents are used. No data are available for the minimum alveolar concentration (MAC) requirements in such patients or in animal models of sepsis. We have characterized the effect of sepsis on the MAC of isoflurane in a normotensive rodent model of sepsis. The minimum inhibitory concentration (MIC) of isoflurane to an identical stimulus was determined for rodents subjected to caecal ligation and perforation (CLP n = 8), or sham laparotomy (n = 7). The calculated MAC of isoflurane was reduced in the septic animals compared with the sham animals (MAC of isoflurane, CLP = 0.8%, sham = 1.4% P < 0.003). No statistical differences were found in the haemodynamic variables measured in either group. Isoflurane leads to haemodynamic stability during anaesthesia in this animal model of sepsis. However, the MAC requirement for isoflurane is reduced by sepsis.
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PMID:Sepsis reduces isoflurane MAC in a normotensive animal model of sepsis. 755 4

The transcription factors C/EBP alpha and C/EBP beta belong to the leucine-zipper C/EBP (CCAAT/enhancer binding protein) family of DNA-binding proteins. C/EBP alpha and C/EBP beta are expressed in the liver and are implicated in the control of transcriptional events following following sepsis. It is hypothesized that inhibition of C/EBP alpha gene expression following sepsis may lead to some of the phenotypic features we recognize as sepsis syndrome such as decreased visceral protein (albumin) synthesis. In this study we demonstrate that C/EBP alpha mRNA accumulation is transiently inhibited 12 hr following peritoneal insult, consistent with previous data. However, we demonstrate that (1) there is increased binding of hepatic nuclear protein to the C/EBP alpha DNA response element 48 hr following insult, (2) a marked increase in C/EBP alpha protein is observed 48 hr following CLP insult compared with no increase in hepatic C/EBP alpha protein at 12 hr postinsult, (3) the increase in hepatic C/EBP alpha protein at 48 hr following cecal ligation and puncture is not associated with an increase in C/EBP alpha mRNA accumulation, (4) the increase in hepatic C/EBP alpha protein is associated with an increase in C/EBP beta protein, and (5) hepatic albumin mRNA accumulation is decreased at 12 and 48 hr following insult and does not correlate with the C/EBP alpha protein synthesis. We conclude that the possible role of the transcription factor C/EBP alpha with respect to decreased albumin gene expression following sepsis must be reevaluated.
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PMID:Regulation of the transcription factor C/EBP alpha following peritoneal sepsis. 756 18

Thymic programmed cell death (PCD) or apoptosis (Ao) is elevated during inflammation by a variety of stressors in vitro (i.e., glucocorticoids, tumor necrosis factor (TNF), prostanoids, etc.), however, little or no information is available concerning its presence in polymicrobial sepsis. To establish whether or not PCD is accelerated in the thymus following the onset of sepsis, thymocytes were harvested from C3H/HeN mice at 1, 2, 12, and 24 h following cecal ligation and puncture (CLP; to induce sepsis) or Sham-CLP (Sham), and assessed for changes in thymocyte viable cell yield, increased Ao + cells based on FACS analysis (propidium iodide staining) or by evidence of fragmentation of the genomic DNA. The results indicate that at 1 h post-CLP there were no marked changes in any of these parameters. However, by 4 h post-CLP the percentage of Ao + thymocytes increased and the septic mouse genomic DNA exhibited trace amounts of fragmentation. These changes increased in the septic animals cells through both 12 and 24 h. Alternatively, thymic viable cell yield did not significantly decrease until 12 h. Marked changes in systemic mediators, corticosterone and TNF, were also detected in septic mouse blood at all time points. In an effort to determine the contribution of these two agents to the induction of the accelerated PCD seen here, mice were randomized to receive either RU-38486 (11 beta-[p-(dimethylamino)phenyl]-17 beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one (Mifepristone); a steroid receptor blocker), polyethylene glycol (PEG)-(rsTNF-R1)2 (a TNF inhibitor) immediately following CLP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The induction of accelerated thymic programmed cell death during polymicrobial sepsis: control by corticosteroids but not tumor necrosis factor. 760 Jan 93

Sepsis increases phosphocreatine (PCr) breakdown and reduces PCr stores in skeletal muscle. To determine if systemic infection impairs mitochondrial function, in vivo 13P magnetic resonance spectroscopy (31P MRS) studies of the gastrocnemius muscle were performed in virus-free male Wistar rats 24 or 48 hr after cecal ligation and 18-gauge needle single puncture (24 degrees CLP, n = 16; 48 degrees CLP, n = 15) or sham operation (24 degrees SHAM, n = 18; 48 degrees SHAM, n = 13). Physiologic saline (6 ml/100 g body wt) was injected intraperitoneally for fluid resuscitation. Water but no food was allowed in all animals. High resolution (8.45 Tesla) 31P MRS spectra, obtained at rest and during exercise using a 1.4-cm surface coil, were used to calculate PCr/ATP, PCr/P(i) ratios, and intracellular pH. Steady-state muscle exercise was induced by supramaximal sciatic nerve stimulation at 10 Hz for 10 min. Recovery of PCr/(PCr + P(i)) ratios after exercise was fitted to a monoexponential curve. The resultant function was used to calculate the half time for PCr recovery, the initial PCr resynthesis rate, and the maximal oxidative ATP synthesis rate, which reflect the rephosphorylation of ADP and are therefore measures of mitochondrial oxidative capacity. PCr/ATP ratios decreased by 12 and 11%, 24 and 48 hr after CLP, respectively. The PCr/P(i) ratios decreased incrementally (7% in 24 degrees CLP vs 23% in 48 degrees CLP animals). Twenty-four hours after operation the half time for PCr recovery was shortened while the initial PCr resynthesis rate and maximal oxidative ATP synthesis rate were accelerated in CLP animals compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The duration of infection modifies mitochondrial oxidative capacity in rat skeletal muscle. 763 Jan 22

The present work showed that cardiac sarcolemmal (SL) adenylyl cyclase (AC) and purified AC maximal activity of septic rat (cecal ligaation and puncture, CLP) were significantly increased during the early sepsis (ES, CLP 9 h) but decreased in the late sepsis (LS, CLP 18 h). Similar alterations were observed in cardiac sarcolemmal protein kinase C (PKC) activity. Sensitization and desensitization of rat SL adenylyl cyclase during ES and LS were respectively correlated with activition and inhibition of PKC. The biphasic changes of AC and PKC were independent of beta- and alpha 1-adrenergic receptor systems. The rat cardiac sarcolemmal PKC activation and AC sensitization during ES is related to M-cholinergic receptor system. The system, however, is not involved during the LS PKC inhibition and AC desensitization.
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PMID:[A study on the mechanism of the cardiac adenylyl cyclase activity alteration in septic rats]. 765 91

Sepsis/septic shock and multiple organ failure are important causes of morbidity and mortality. Our objective was to study sepsis and organ failure in a fluid-resuscitated septic model. Males S-D rats were anesthetized with halothane, the jugular vein catheterized, and CLP performed. Each rat was maintained in a metabolism cage on continuous intravenous fluid (3 mL/rat). Urine rate and [creatinine]urine were measured daily. At day 5, serum creatinine with chemistry profile, complete blood count, clotting times, and wet lung/body weight ratios were also measured. Glomerular filtration rate (GFR) was measured according to the principle of endogenous creatinine clearance. GFR was correlated with the product of urine rate x [creatinine]urine (R = .79), so that product was used as a daily indicator of GFR. Urine output remained > or = normal during sepsis. Heparin and antithrombin III were tested in this model. The model was associated with 40% mortality, a 60% reduction in platelet count, liver damage, a 75% reduction in renal function, muscle damage, and a normal wet lung/body weight ratio. Treatment with heparin/antithrombin III ameliorated the decrease in GFR (p < .05) observed in the nontreated animals, prevented the septic-induced thrombocytopenia (p < .05), and improved survival (p = .05).
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PMID:The efficacy of heparin and antithrombin III in fluid-resuscitated cecal ligation and puncture. 774 74

Studies indicate that hepatocellular dysfunction occurs at 2 h after cecal ligation and puncture (CLP, i.e., sepsis model) despite the increased cardiac output (CO) and hepatic perfusion. It, however, remains unknown whether hepatocellular function is depressed earlier than the onset of hyperdynamic circulation in sepsis. To determine this, rats were subjected to sepsis by CLP. At .5, 1, 1.5, or 2 h after CLP, CO was measured by dye dilution. Hepatocellular function (i.e., maximum velocity of indocyanine green clearance and the efficiency of the active transport) was determined using an in vivo indocyanine green clearance technique. Microvascular blood flow was measured by laser Doppler flowmetry. To determine whether there is any association between hemodynamics and prostaglandins (PGs), plasma levels of PGE2 and PGI2 were measured by radioimmunoassay. The results indicate that hepatocellular function decreased significantly as early as 1.5 h after CLP. Cardiac output and microvascular blood flow in the liver and small intestine, however, increased and vascular resistance decreased at 2 h after CLP. Thus, hepatocellular dysfunction occurs earlier than the occurrence of hyperdynamic circulation during sepsis. Although circulating PGE2 levels were not altered, plasma PGI2 increased significantly at 2 h after CLP. The elevated circulating PGI2 levels, therefore, may be partially responsible for the decreased vascular resistance and increased tissue perfusion at 2 h after CLP. Our findings also suggest that cellular dysfunction, observed in the very early stage of sepsis, is not due to any hyperdynamic circulation/hypermetabolism-related events, but may be associated with the release of proinflammatory cytokines.
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PMID:Hepatocellular dysfunction occurs earlier than the onset of hyperdynamic circulation during sepsis. 785 May 75

These studies demonstrate clearly that the creation of donor-specific tolerance in animals permits the long-term survival of incompatible skin grafts placed following a burn with early eschar excision. Furthermore, the studies demonstrate graphically that such replacement can be done without any increase in the septic mortality in these animals and strongly suggest that such a treatment would be potentially efficacious as a therapy for large body burns that could not be successfully covered with autografts. When animals were observed either in the potentially septic milieu of a large 30% body burn or in a situation of a deliberate attempt to create a septic state using the septic challenge of CLP, the placement of a full-thickness skin graft that survived was clearly beneficial to the animal in reducing mortality. In addition, the donor-specific tolerance technique described permits long-term survival of these skin grafts, which in some of the earlier laboratory studies were able to survive permanently and might well achieve permanent survival in a clinical situation. However, a prolonged graft survival of 90 to 100 days, considering the ability to develop new split thickness skin grafts providing dermal cover at 20- to 25-day intervals, would provide opportunity for a least four "croppings" of the skins. Thus, for example, a small area of remaining autograft skin of 20% in an 80% burn patient could potentially be cropped four times to achieve close to 80% coverage. Coverage would be easier and more successful in the more common burns of less than 70% of TBSA. It is of interest to us that there is virtually no well-developed literature on the use of donor-specific tolerance to aid skin graft survival. There would seem to be a reasonable rationale for considering such therapy since septic problems should not be significantly increased during induction of skin graft tolerance. Once the skin grafting has produced a significant increase in functionally covered skin, the risk of sepsis should decrease markedly. Because sepsis is currently the major factor in 75% of burn deaths, donor-specific tolerance for skins grafts appears to be eminently reasonable for future consideration. Expanded animal studies are probably necessary before clinical trials are undertaken, although skin grafting with immunosuppression has already been tried in patients.
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PMID:Improved large burn therapy with reduced mortality following an associated septic challenge by early excision and skin allografting using donor-specific tolerance. 787 31


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