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)

Fasciolosis is recognized as an important human disease. Wistar rats experimentally infected with Fasciola hepatica were examined using data obtained in the advanced chronic state of the disease (200, 300 and 400 days post-infection, dpi). Pigment stones (PS) and bile specimens were collected. The same procedure was applied in control rats. Liver tests were determined using stored serum samples. Bacteriological bile culture revealed viable bacteria (Escherichia coli, 45% of cases, Enterococcus faecalis, 45% and Klebsiella pneumoniae, 10%). The presence of bacterobilia was associated with liver serum enzymes, including aspartate aminotransferase (AST or SGOT), alanine aminotransferase (ALT or SGPT), alkaline phosphatase (AP) and total bilirubin levels. Multivariate analysis suggested an association between bacterobilia and the following factors: duration of parasitic infection and intensity of parasitic infection supported the impression that the obstruction caused by advanced chronic fasciolosis in the rat may be related to biliary sepsis. Extrapolation to human infection in fasciolosis hyperendemic areas is discussed. In conclusion, the results of the rodent model should lead to a reconsideration of treatment features in human disease, i.e. therapeutic strategies should not only include a parasitic treatment but also consider the possibility of bacterial co-infection.
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PMID:High risk of bacterobilia in advanced experimental chronic fasciolosis. 1706 56

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

The liver can be injured and its functions altered by activation of the coagulation and inflammatory processes in sepsis. The objective of the present study was to investigate the pattern of protease- activated receptors (PARs) over time in a model of acute liver injury induced by lipopolysaccharide (LPS); and whether PARs play a role in this process and exert their effects through inflammation and coagulation. Levels of tumor necrosis factor-a (TNF-a) were significantly expressed 1 h after LPS administration followed by: i) an increase in levels of tissue factor, factor VIIa, thrombin and plasminogen activator inhibitor-1; ii) unchanged or steady levels of tissue factor pathway inhibitor; and iii) subsequent deposition of fibrin in the liver tissue, that led to the elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are associated with liver injury. The expression of all PAR isoforms (1-4) was elevated, and each isoform had a distinct cellular localization (hepatocytes, Kupffer cells, the portal triad area, and central veins) and a time-dependent pattern of expression. The immuno-reactivity of PAR2 and 4 in Kupffer cells was intense. Interestingly, PAR2 blocking peptide improved the healing of liver injuries, an effect that was associated with suppression of TNF-a elevation, and normalization of coagulation and fibrinolysis. This ultimately led to decreased fibrin formation in the injured liver. The present study reveals a distinct chronological expression and cellular localization of PARs in LPS-mediated liver injury and shows that blockade of PAR2 may play a crucial role in treating liver injury, via normalization of inflammation, coagulation and fibrinolytic pathways.
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PMID:Chronological expression of PAR isoforms in acute liver injury and its amelioration by PAR2 blockade in a rat model of sepsis. 1713 80

Cholestasis is a major complication in sepsis although the underlying mechanisms remain elusive. The aim of this study was to evaluate the role of P-selectin and leukocyte recruitment in endotoxemia-associated cholestasis. C57BL/6 mice were challenged intraperitoneally with endotoxin (0.4 mg/kg), and 6 h later the common bile duct was cannulated for determination of bile flow and biliary excretion of bromosulfophthalein. Mice were pretreated with an anti-P-selectin antibody or an isotype-matched control antibody. Leukocyte infiltration was determined by measuring hepatic levels of myeloperoxidase. Tumor necrosis factor-alpha and CXC chemokines in the liver was determined by ELISA. Liver damage was monitored by measuring serum levels of alanine aminotransferase and aspartate aminotransferase. Apoptosis was quantified morphologically by nuclear condensation and fragmentation using Hoechst 33342 staining. Endotoxin induced a significant inflammatory response with increased TNF-alpha and CXC chemokine concentrations, leukocyte infiltration, liver enzyme release, and apoptotic cell death. This response was associated with pronounced cholestasis indicated by a >70% decrease of bile flow and biliary excretion of bromosulfophthalein. Immunoneutralization of P-selectin significantly attenuated endotoxin-induced leukocyte infiltration reflected by a >60% reduction of hepatic myeloperoxidase levels. Interference with P-selectin decreased endotoxin-mediated hepatocellular apoptosis and necrosis, but did not affect hepatic levels of tumor necrosis factor-alpha and CXC chemokines. Of interest, inhibition of P-selectin restored bile flow and biliary excretion of bromosulfophthalein to normal levels in endotoxin-challenged animals. Our study demonstrates for the first time that P-selectin-mediated recruitment of leukocytes, but not the local production of proinflammatory mediators, is the primary cause of cholestasis in septic liver injury.
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PMID:Sepsis-associated cholestasis is critically dependent on P-selectin-dependent leukocyte recruitment in mice. 1725 63

Severe burn induces the activation of an inflammatory cascade that contributes to the development of subsequent immunosuppression, increased susceptibility to sepsis, as well as generation of reactive oxygen radicals and lipid peroxidation, leading to multiple organ failure. In the present study, we investigated whether rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand is protective against burn-induced remote organ injury. Under brief ether anaesthesia, shaved dorsum of the rats were exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10s. Rosiglitazone (4 mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn. Rats were decapitated 24h after injury and the tissue samples from lung, liver, and kidney were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, and creatinine, blood urea concentrations (BUN) were determined to assess liver and kidney function, respectively. Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and lactate dehydrogenase (LDH) were also assayed. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, and significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum ALT, AST and BUN levels, as well as LDH, IL-1 beta and TNF-alpha were elevated in the burn group as compared to the control group. Rosiglitazone treatment reversed all these biochemical indices. According to the findings of the present study, rosiglitazone possesses a anti-inflammatory effect that prevents burn-induced damage in remote organs and protects against organ damage.
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PMID:Rosiglitazone, a PPAR-gamma ligand, protects against burn-induced oxidative injury of remote organs. 1746 12

Sepsis is the leading cause of death for intensive care patients. Lipopolysaccharide (LPS) administration to animals under anesthesia is a strategy for the study of uncontrolled release of proinflammatory cytokines. Anesthetics have been indicated that they can specially affect immune responses, such as the inflammatory response. Pentobarbital is an anesthetic used mainly in animal studies. Thus, the effect of pentobarbital on tumor necrosis factor-alpha (TNF-alpha) release was determined. The results revealed that pentobarbital suppressed the expression of TNF-alpha mRNA and its proteins, which may result from the decrease in the activities of nuclear factor-kappaB and activator protein 1 and the reduction of the expression of p38 mitogen-activated protein kinase by pentobarbital. After the inhibitory activity of the pentobarbital for TNF-alpha release was proven in vivo, the cytotoxic effects of LPS were examined in vivo with or without pentobarbital treatments. In vivo results indicated that plasma levels of alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, creatine kinase, serum urea nitrogen, and amylase decreased dramatically in the anesthetic group with pentobarbital administration. Finally, the effect of pentobarbital on TNF-alpha-related cell death was monitored in vitro, and the results indicated the pentobarbital could directly enhance the viabilities of cells under the treatment of TNF-alpha and protected cells from apoptosis induced by deferoxamine mesylate-induced hypoxia. These results suggest that pentobarbital significantly influences the LPS-induced inflammatory response and protects cells from death directly and indirectly induced by TNF-alpha. The information provides a perspective to re-evaluate the results of the experiments in which animals were anesthetized with pentobarbital. The anti-inflammatory effects of the drugs may have been caused by the synergistic effect of pentobarbital.
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PMID:The reduction of tumor necrosis factor-alpha release and tissue damage by pentobarbital in the experimental endotoxemia model. 1754 46

Transient potential vanilloid 1 (TRPV1) receptor is an ion channel receptor primarily localized on sensory nerves and activated by specific stimuli to initiate and amplify pain and inflammation, as typified by murine models of scald and arthritis. Little is known of the role of TRPV1 in sepsis, an infective disease associated with inflammation. Through use of a sublethal murine model of lipopolysaccharide-induced peritoneal sepsis, we provide novel evidence that genetic deletion of TRPV1 leads to an enhanced onset of various pathological components of systemic endotoxemia. Paired studies of TRPV1 knockout (KO) and wild-type mice demonstrate significantly enhanced hypotension (56+/-2% vs. 38+/-6% decrease in blood pressure, n=12), hypothermia (13+/-3% vs. 7+/-1% decrease in core temperature, n=6), and peritoneal exudate mediator levels (TNF-alpha, 0.78+/-0.2 vs. 0.38+/-0.1 ng/ml; nitrite, for NO, 35+/-10 vs. 15+/-3 microM; n=8) in TRPV1 KO mice, indicating loss of protective effect. Findings correlated with liver edema and raised plasma levels of aspartate aminotransferase in TRPV1 KO mice. These data suggest that TRPV1 may play an important regulatory role in sepsis independent of the major sensory neuropeptide substance P. The findings are relevant to developing strategies that increase the beneficial, and reduce the harmful, components of sepsis to prevent and treat this often fatal condition.
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PMID:The transient receptor potential vanilloid 1 (TRPV1) receptor protects against the onset of sepsis after endotoxin. 1760 84

To investigate clinical course and outcome of dengue with acute respiratory failure (ARF), and to identify related risk factors for acquiring ARF in dengue, we retrospectively studied 11 dengue patients with ARF. From June to December 2002, a total of 606 adult patients were diagnosed as having dengue. Eleven (1.8%) of 606 dengue patients had complications of ARF. The main causes of ARF were sepsis (n = 6, 54.5%) and upper gastrointestinal (UGI) bleeding (n = 3, 27.3%). The mortality rate was 72.7% (n = 8). Additionally, univariate analysis showed that age, dyspnea, cough, prothrombin time, activated partial thromboplastin time, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, albumin, renal insufficiency, acute renal failure, acute hepatic failure, UGI bleeding, and combination bacterial infection were significantly predictive variables associated with dengue patients with ARF.
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PMID:Acute respiratory failure in adult patients with dengue virus infection. 1762 Jun 47

Biliary complications after liver transplantation (LT) using organs retrieved from donors after cardiac death are not well characterized. The aim of this study was to evaluate the severity of biliary complications and outcomes after donation after cardiac death liver transplantation (DCD-LT). A retrospective evaluation of 20 DCD-LTs from 1997-2006 was performed. The recipient age was 53+/-8.7, and the donor age was 35+/-11 years. The warm ischemia time, cold ischemia time, peak alanine aminotransferase level, and peak aspartate aminotransferase level were 33+/-12 minutes, 8.7+/-2.7 hours, 1757+/-1477 U/L, and 4020+/-3693 U/L, respectively. The bilirubin and alkaline phosphatase levels at hospital discharge after LT were 3.2+/-5.4 mg/dL and 248+/-200 U/L, respectively. During a median follow-up of 7.5 months (range: 1-73), 5 patients (25%; 1 death after re-LT) died (3 from sepsis, 1 from recurrent hepatocellular carcinoma at 4 months, and 1 from a cardiac event at 46 months), and additionally, 4 patients (20%) required re-LT (1 because of hepatic artery thrombosis, 1 because of primary graft nonfunction, and 2 because of biliary strictures). Twelve (60%) developed biliary complications, and of these, 11 (55%) had serious biliary complications. The biliary complications were as follows: a major bile leak for 2 patients (10%; both eventually underwent retransplantation), anastomotic strictures for 5 patients (25%), hilar strictures for 7 patients (35%), extrahepatic donor duct strictures for 9 patients (45%), intrahepatic strictures for 10 patients (50%), stones for 1 patients (5%), casts for 7 patients (35%), and debris for 2 patients (10%). More than 1 biliary complication was seen in most patients, and these were unpredictable and required multiple diagnostic or therapeutic procedures. Serious biliary complications are common after DCD-LT, and research should focus on identifying donor and recipient factors that predict and prevent serious biliary complications.
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PMID:Biliary complications and outcomes of liver transplantation from donors after cardiac death. 1804 64

IL-19, a proinflammatory cytokine, belongs to the IL-10 family. IL-19 is induced in systemic inflammatory response syndrome, but its pathophysiological function in sepsis is unclear. Our aim was to determine the roles of IL-19 in endotoxin-induced tissue damage in vivo and in vitro. We examined serum levels of IL-19 in sepsis patients and healthy volunteers, determined the in vitro effects of IL-19 on lung epithelial cells, liver cells, and neutrophils, and analyzed the tissue expression of IL-19 and its receptors in murine endotoxic shock. Electroporation-mediated gene transfer of mouse IL-19-soluble receptor plasmid DNA was used to determine the effects of IL-19 depletion in preventing endotoxic shock-induced tissue damage in mice. We found that serum levels of IL-19 were higher in patients than in healthy volunteers (n = 28, P = 0.001). IL-19 induced apoptosis in lung epithelial cells and reactive oxygen species production in liver cells in vitro. IL-19 also promoted neutrophil chemotaxis, reduced neutrophil apoptosis, and induced the production of proinflammatory cytokines and chemokines (IL-1[beta], IL-6, IL-8, CCL5, and CXCL9) in lung epithelial cells. In LPS-challenged mice, transcripts of IL-19 and its receptors were up-regulated in heart, lung, liver, and kidney tissue. Neutrophil infiltration in lung and liver tissue, and serum levels of alanine transaminase and aspartate transaminase, were lower in mice electroporated with IL-19-soluble receptor plasmid DNA before LPS treatment compared with control mice. These results suggest that up-regulated IL-19 may be involved in lung and liver tissue injury in murine endotoxic shock.
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PMID:IL-19 is involved in the pathogenesis of endotoxic shock. 1824 2


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