Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of TNF-binding protein (TNFBP) on regulatory mechanisms of muscle protein synthesis during sepsis in four groups of rats: Control; Control+TNFBP; Septic; and Septic+TNFBP. Saline (1. 0 ml) or TNFBP (1 mg/kg, 1.0 ml) was injected daily starting 4 h before the induction of sepsis. The effect of TNFBP on gastrocnemius weight, protein content, and the rate of protein synthesis was examined 5 days later. Sepsis reduced the rate of protein synthesis by 35% relative to controls by depressing translational efficiency. Decreases in protein synthesis were accompanied by similar reductions in protein content and muscle weight. Treatment of septic animals with TNFBP for 5 days prevented the sepsis-induced inhibition of protein synthesis and restored translational efficiency to control values. TNFBP treatment of Control rats for 5 days was without effect on muscle protein content or protein synthesis. We also assessed potential mechanisms regulating translational efficiency. The phosphorylation state of p70(S6) kinase was not altered by sepsis. Sepsis reduced the gastrocnemius content of eukaryotic initiation factor 2Bepsilon (eIF2Bepsilon), but not eIF2alpha. The decrease in eIF2Bepsilon content was prevented by treatment of septic rats with TNFBP. TNFBP ameliorates the sepsis-induced changes in protein metabolism in gastrocnemius, indicating a role for TNF in the septic process. The data suggest that TNF may impair muscle protein synthesis by reducing expression of specific initiation factors during sepsis.
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PMID:TNF-binding protein ameliorates inhibition of skeletal muscle protein synthesis during sepsis. 1019 95

Chronic abdominal sepsis is associated with impaired tissue repair. Treatment of burn patients with growth hormone results in improved healing of skin graft donor sites. The goal of this study was to determine whether administration of growth hormone could attenuate the inhibitory effects of sepsis on cutaneous wound healing. Four groups of male Sprague Dawley rats were studied: control, control + growth hormone, sepsis, and sepsis + growth hormone. Sepsis was caused by implantation of a bacterial focus in the peritoneal cavity. Control animals underwent sham laparotomy, and polyvinyl alcohol sponge implants were placed in subdermal pockets in all animals. Saline or growth hormone (400 microg) was injected subcutaneously every 12 hours. On day 5, the incisional wounds and polyvinyl alcohol sponge implants were harvested. The breaking strength of abdominal incisions was measured. Granulation tissue penetration and quality were determined by scoring polyvinyl alcohol sponge implant histology from 1 to 4 in a blinded fashion. Collagen deposition in polyvinyl alcohol sponge implants was quantitated by hydroxyproline assay. Septic mortality was not altered by growth hormone administration. Septic animals showed a reduction in food consumption for 2 days after surgery (p < 0.05 vs. controls), which was not affected by growth hormone administration. The breaking strength of incisional wounds and hydroxyproline content of polyvinyl alcohol sponge implants was reduced in septic rats (p < 0.001 vs. controls) but administration of growth hormone for 5 days did not improve breaking strength or collagen deposition in either group. We conclude that the administration of growth hormone for 5 days did not improve collagen deposition or breaking strength in cutaneous wounds from control or septic animals. The results suggest that growth hormone treatment is unlikely to improve tissue repair in sepsis-induced catabolic illness.
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PMID:Growth hormone does not attenuate the inhibitory effects of sepsis on wound healing. 1081 36

The efficacy of ornithine alpha-ketoglutarate (OKG) in preventing bacterial translocation and dissemination, metabolic disorders and changes in mucosal enzyme activities was assessed in a model of bacterial translocation in rats. Antibiotic decontamination was performed 4 d before intragastric inoculation with an Escherichia coli strain (10(10) bacteria/kg body). Two days later, the rats were given either a lipopolysaccharide (LPS) 0127:B8 or a saline injection and were deprived of food for 24 h. Enteral nutrition, [Osmolite, 880 kJ/(kg. d)] supplemented with either OKG (LPS + OKG) or glycine (Saline + Gly or LPS + Gly), was then given for 2 d. Urinary total nitrogen losses and 3-methylhistidine excretion were determined daily. On killing at d 3, bacterial translocation to the mesenteric lymph nodes (MLN) and dissemination to the spleen and liver were evaluated, jejunal mucosa enzyme activities were assayed and tissue free amino acids in muscles were measured. Endotoxin induced translocation from the gut lumen to the MLN in all groups, whereas dissemination occurred only in LPS-treated rats. OKG significantly reduced dissemination of the bacteria in the spleen. 3-Methylhistidine excretion was greater in the LPS + Gly group (+25%, P: < 0.05) than in either the LPS + OKG or Saline + Gly group. The group fed the OKG-enriched diet had higher muscular glutamine, ornithine and arginine concentrations than did the Gly-supplemented groups (P: < 0.05). Intestinal sucrase and aminopeptidase activities were higher in the LPS + OKG group than in the LPS + Gly group (-30%, P: < 0.05). OKG supplementation limits bacterial dissemination and metabolic changes after injury in rats and thus may be useful in the prevention of gut-derived sepsis in critically ill patients.
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PMID:Bacterial dissemination and metabolic changes in rats induced by endotoxemia following intestinal E. coli overgrowth are reduced by ornithine alpha-ketoglutarate administration. 1111 Aug 43

Obstructive jaundice is associated with high morbidity and mortality. Major complications such as pulmonary dysfunction, renal failure and sepsis are frequently encountered. Recent studies and observations suggest that the free oxygen radicals (FORs) produced in obstructive jaundice may play a significant role in the etiopathogenesis of acute renal failure (ARF). Thirty rats were divided into three groups, as sham, control and treatment groups containing 10 rats each. Laparatomy was performed on each animal in the control and treatment groups and common bile ducts were ligated. Common bile duct was observed but was not ligated for the rats in the sham group. Saline solution injection was begun on the first day of surgical procedure and repeated once a day during the following 5 days. The same procedure was performed with oxygen radical scavenger dimethyl sulfoxide (1.5 mg/kg/day i.p.) instead of saline in the treatment group. The rats were sacrificed on the 7th postoperative day. On the 7th postoperative day, the bilirubin, urea and creatinine levels of the control and treatment groups were significantly higher in comparison with the sham group (p < 0.01). Although there was no statistically significant difference between the bilirubin levels of the control and treatment groups (p > 0.05), the urea and creatinine levels in the treatment group were significantly lower (p < 0.01). On the 7th postoperative day, the erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels of the control and treatment groups were significantly lower than those of the sham group (p < 0.01), whereas renal and erythrocyte malondialdehyde (MDA) levels were significantly higher (p < 0.01). Although SOD and GSH-Px levels did not differ significantly between the treatment and control groups (p > 0.05), renal and erythrocyte MDA levels of the treatment group were significantly lower than those of the control group (p < 0.01). The histopathological scores were significantly higher in the control and treatment groups (p < 0.01); there was no significant difference between the control and treatment groups (p > 0.05). FORs seem to play a significant role in the etiopathogenesis of renal failure in obstructive jaundice. Antioxidant treatment may decrease oxidative damage due to FORs and may prevent renal failure.
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PMID:Role of oxygen free radical scavengers in acute renal failure complicating obstructive jaundice. 1274 May 34

Lipopolysaccharide (LPS) contributes importantly to morbidity and mortality in sepsis. Bovine intestinal alkaline phosphatase (BIAP) was demonstrated to detoxify LPS through dephosphorylation. LPS injection combined with BIAP reduced inflammation and improved survival in various experimental settings. In this study, single-dose intravenous administration of BIAP (0.15 IU/g) was applied in a murine cecal ligation and puncture (CLP) model of polymicrobial sepsis. Saline was given as control (S group). Treatment with BIAP prior to CLP (prophylaxis; BIAP-P group) or shortly after (early treatment; BIAP-ET group) reduced cytokine concentrations in plasma and peritoneal lavage fluid (PLF). Tumor necrosis factor-alpha peak levels decreased from 170 pg/ml (S) to 57.5 (BIAP-P) and 82.5 (BIAP-ET) in plasma and in PLF from 57.5 pg/ml (S) to 35.3 (BIAP-P) and 16.8 (BIAP-ET) (all, P < 0.05). Peak interleukin-6 levels in plasma decreased from 19.3 ng/ml (S) to 3.4 (BIAP-P) and 11.5 (BIAP-ET) and in PLF from 32.6 ng/ml (S) to 13.4 (BIAP-P) and 10.9 (BIAP-ET) (all, P < 0.05). Macrophage chemoattractant protein 1 peak levels in plasma decreased from 2.0 ng/ml (S) to 1.0 (BIAP-P) and 0.7 (BIAP-ET) and in PLF from 6.4 (S) to 2.3 (BIAP-P) and 1.3 ng/ml (BIAP-ET) (all, P < 0.05). BIAP-treated groups showed decreased transaminase activity in plasma and decreased myeloperoxidase activity in the lung, indicating reduced associated hepatocellular and pulmonary damage. Survival was not significantly altered by BIAP in this single-dose regimen. In polymicrobial secondary peritonitis, both prophylactic and early BIAP treatment attenuates the inflammatory response both locally and systemically and reduces associated liver and lung damage.
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PMID:Bovine intestinal alkaline phosphatase attenuates the inflammatory response in secondary peritonitis in mice. 1597 24

Sepsis is associated with an activation of the coagulation system and multiorgan failure. The aim of the study was to examine the effects of selective thrombin inhibition with melagatran on renal hemodynamics and function, and liver integrity, during early endotoxemia. Endotoxemia was induced in thiobutabarbital-anesthetized rats by an intravenous bolus dose of lipopolysaccharide (LPS; 6 mg/kg). Sham-Saline, LPS-Saline, and LPS-Melagatran study groups received isotonic saline or melagatran immediately before (0.75 micromol/kg iv) and continuously during (0.75 micromol.kg(-1).h(-1) iv) 4.5 h of endotoxemia. Kidney function, renal blood flow (RBF), and intrarenal cortical and outer medullary perfusion (OMLDF) measured by laser-Doppler flowmetry were analyzed throughout. Markers of liver injury and tumor necrosis factor (TNF)-alpha were measured in plasma after 4.5 h of endotoxemia. In addition, liver histology and gene expression were examined. Melagatran treatment prevented the decline in OMLDF observed in the LPS-Saline group (P < 0.05, LPS-Melagatran vs. LPS-Saline). However, melagatran did not ameliorate reductions in mean arterial pressure, RBF, renal cortical perfusion, and glomerular filtration rate or attenuate tubular dysfunctions during endotoxemia. Melagatran reduced the elevated plasma concentrations of aspartate aminotransferase (-34 +/- 11%, P < 0.05), alanine aminotransferase (-21 +/- 7%, P < 0.05), bilirubin (-44 +/- 9%, P < 0.05), and TNF-alpha (-32 +/- 14%, P < 0.05) in endotoxemia. Melagatran did not diminish histological abnormalities in the liver or the elevated hepatic gene expression of TNF-alpha, intercellular adhesion molecule-1, and inducible nitric oxide synthase in endotoxemic rats. In summary, thrombin inhibition with melagatran preserved renal OMLDF, attenuated liver dysfunction, and reduced plasma TNF-alpha levels during early endotoxemia.
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PMID:Effects of thrombin inhibition with melagatran on renal hemodynamics and function and liver integrity during early endotoxemia. 1706 59

Acute renal failure during human sepsis is often nonoliguric. To study the underlying mechanisms, renal function was assessed in endotoxic and control male Wistar rats during and after saline loading and treatment with the selective V2 receptor agonist desmopressin. Escherichia coli endotoxin (dose, 8 mg/kg) was administered from time (t)=0 to t=60 min; saline loading (rate, 5 mL/100 g per hour) was administered from t=0 to t=120 min. Thereafter, half of each group received desmopressin (dose, 10 microg) for 1 h. The inner medullary (IM) osmolality, hematocrit, plasma, and urinary concentrations of sodium, potassium, urea, and osmolality were measured; then, aquaporin 2 (AQP2) immunohistochemistry was performed. Plasma vasopressin concentrations were measured at t=180 min. Saline loading increased urine volume in all rats. In the endotoxic group, mean arterial pressure decreased when saline loading was stopped. Despite increased hematocrit and vasopressin levels (>16 pg/mL), the endotoxin group had a low IM osmolality (mean +/- SEM, 412+/-0.04 mOsm/kg H2O) in comparison with the control group (mean +/- SEM, 1,094+/-0.17 mOsm/kg H2O) and was not able to either decrease urine volume or raise urine osmolality. Desmopressin treatment in endotoxin-treated rats maintained mean arterial pressure, increased sodium reabsorption, IM osmolality, and urine osmolality, and decreased urine flow. The AQP2 intensity decreased in the endotoxin group, and the apical localization disappeared; both were not affected by desmopressin. Our results indicate that endotoxemia in rats acutely diminishes renal urinary concentration capacity and is associated with a decreased IM osmolality and diminished apical AQP2 localization. These findings may help to explain nonoliguric acute renal failure in human septic shock.
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PMID:Mechanisms of the urinary concentration defect and effect of desmopressin during endotoxemia in rats. 1769 23

Clinical studies indicate potential differences in the efficacy of immunoglobulin (Ig) preparations in patients with sepsis. A recent meta-analysis showed improved survival rates with IgM-enriched Igs. It was the objective of the present study to characterize microcirculatory actions of different clinically used Ig preparations in a rodent endotoxin model by intravital microscopy. Male Syrian golden hamsters 6 to 8 weeks old with a body weight of 60 to 80 g were investigated by intravital fluorescence microscopy. Endotoxemia was induced by administration of 2 mg/kg (i.v.) endotoxin (LPS, Escherichia coli). Two different Ig preparations containing IgM, IgA, and IgG (intravenous IgM group; n = 6; 5 mL Pentaglobin/kg body weight, i.v.) or exclusively IgG (intravenous IgG group; n = 5; 5 mL Flebogamma/kg body weight, i.v.) were applied 5 min before LPS. Saline-treated endotoxemic animals served as controls (control; n = 8). In controls, LPS induced massive leukocyte-endothelial cell interactions, pronounced microvascular leakage, a decrease of systemic platelet count, and distinct capillary perfusion failure (P < 0.05). Both intravenous IgM and IgG reduced venular leakage (P< 0.05) and ameliorated the decrease in platelet count (P < 0.05). Of interest, intravenous IgM was capable of significantly (P< 0.05) reducing leukocyte adhesion in venules. This was associated with normalization of capillary perfusion at 24 h of endotoxemia, whereas intravenous IgG could not prevent LPS-mediated microvascular perfusion failure. We demonstrate that IgM-enriched Igs are superior to IgG alone in attenuating LPS-induced leukocytic inflammation and microcirculatory dysfunction. Our findings can explain better efficacy of IgM-enriched Igs in patients with severe sepsis.
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PMID:Immunoglobulin M-enriched human intravenous immunoglobulins reduce leukocyte-endothelial cell interactions and attenuate microvascular perfusion failure in normotensive endotoxemia. 1824 4

Albumin has been used for volume resuscitation and supplementation in critically ill patients for over 50 years. While regarded as a "gold standard" colloid solution, albumin is associated with substantial cost, and questions have been raised about its safety and efficacy. A large-scale randomised controlled trial (the Saline vs. Albumin Fluid Evaluation [SAFE] study) demonstrated that albumin and saline were clinically equivalent treatments for intravascular volume resuscitation in a heterogenous population of critically ill patients. However, in patients with traumatic brain injury, albumin was associated with a significantly higher mortality and cannot be recommended for acute resuscitation of such patients. A potential beneficial role of albumin in patients with severe sepsis, particularly malaria, requires further study. Extrapolation of the results of the SAFE study to other, synthetic, colloid solutions requires caution, and a randomised controlled trial comparing albumin, starch and crystalloids in patients with severe sepsis is warranted. The safety of synthetic colloids in patients with traumatic brain injury should not be assumed. Although hypoalbuminaemia is associated with increased mortality, use of albumin for volume resuscitation of critically ill patients with a serum albumin concentration < or =25 g/L is not associated with reductions in mortality, duration of ICU stay or mechanical ventilation, or in use of renal replacement therapy. Similarly, there is no substantive evidence to justify the use of hyperoncotic albumin solutions for resuscitation or supplementation in critically ill patients. Albumin is a safe and effective resuscitation solution in critically ill patients without traumatic brain injury. However, the acquisition costs of albumin and synthetic colloids are more than those of crystalloids, and, as yet, colloids have not been proven to confer substantive benefits over crystalloids such as saline.
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PMID:Albumin is a blood product too - is it safe for all patients? 1928 47

The testis is an immunologically privileged organ. Sertoli cells can form a blood-testis barrier and protect sperm cells from self-immune system attacks. Spermatogenesis may be inhibited by severe illness, bacterial infections and chronic inflammatory diseases but the mechanism(s) is poorly understood. Our objective is to help in understanding such mechanism(s) to develop protective agents against temporary or permanent testicular dysfunction. Lipopolysaccaride (LPS) is used as a model of animal sepsis while L-carnitine (LCR) is used as a protective agent. A total of 60 male Swiss albino rats were divided into four groups (15/group). The control group received Saline; the 2(nd) group was given LCR (500 mg/kg i.p, once). The third group was treated with LPS (5 mg/kg i.p once) and the fourth group received LCR then LPS after three hours. From each group, five rats were used for histopathological examination. Biochemical parameters were assessed in the remaining ten rats. At the end of the experiment, animals were lightly anaesthetized with ether where blood samples were collected and testes were dissected on ice. Sperm count and motility were evaluated from cauda epididymis in each animal. Also, oxidative stress was evaluated by measuring testicular contents of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-HDG, the DNA adduct for oxidative damage) in testicular DNA. The pro-inflammatory mediator nitric oxide (NO) in addition to lactate dehydrogenase (LDHx) isoenzyme-x activity as an indicator for normal spermatozoal metabolism were assessed in testicular homogenate. Serum interlukin (IL)-2 level was also assessed as a marker for T-helper cell function. The obtained data revealed that LPS induced marked reductions in sperm's count and motility, obstruction in seminiferous tubules, hypospermia and dilated congested blood vessels in testicular sections concomitant with decreased testicular GSH content and LDHx activity. Moreover, the testicular levels of MDA, 8-HDG (in testicular DNA) and NO as well as serum IL-2 level were increased. Administration of LCR before LPS returned both sperm count and motility to normal levels. Also, contents of testicular GSH, MDA, 8-HDG and NO returned back to the corresponding control values. In addition, serum IL-2 level as well as histological abnormalities were markedly improved in LCR + LPS-treated rats. In conclusion, LPS increased proinflammatory and oxidative stress markers in the testis leading to a marked testicular dysfunction. L-carnitine administration ameliorates these effects by antioxidant and/or anti-inflammatory mechanisms suggesting a protective role against male infertility in severely infected or septic patients.
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PMID:Pro-inflammatory and oxidative stress pathways which compromise sperm motility and survival may be altered by L-carnitine. 2035 28


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