PURPOSE: To investigate the influence of transforming growth factor-beta
(TGF-beta;) on endotoxin-induced uveitis (EIU).
METHODS: TGF- beta; was abstracted from humam platelets using Bio-gel P-60 chromatography. It was introduced either topically(drops) or intraperitoneally into the SD rats after footpad injection of lipopolysaccbaride(LPS). The inflammation in the anterior uvea was clinically evaluated with slitlamp every day.
RESULTS :TGF-beta; obtained from Biogel P-60 chromatography displayed single band on SDS-PAGE,showing a molecular weight of 12 500 EIU occurs significantly earlier and more severe in the rats which only received LPS injection than in the TGF-beta; treated rats. The duration of the inflammation was also much longer in the untreated rats than in the treated rats (P＜0. 001). CONCLUSION: TGF-beta; purified from human platelets may partly prevent the development of EIU and effectively reduce the severity of the inflammation induced by LPS injection.
（Chin J Ocul Fundus Dis,1996,12: 101-104)
To study the role of endotoxin in acute hemorrhagic necrotizing pancreatitis (AHNP), the change of endotoxin were studied in rats AHNP models by injection of 5% sodium taurocholate 1 ml/kg into pancreatic duct, and the effects of recombinant interleukin-2 (IL-2) in the treatment of AHNP were observed in this experiment. The results indicated that endotoxin involved the aggravation of AHNP and was associated with the increase of serum phospholipas-2 (PLA2), and these mediators were positively correlated with severe degrees of pancreatic damage. The results also suggeste that IL-2 might inhibit the overexpression of endotoxin and PLA2 and mitigate the pancreatic injury and decrease the 72h-mortality rate of AHNP from 66.7% to 26.7% (Ｐ＜0.01). Endotoxin might play a major role in the pathogenesis of AHNP and IL-2 might have a potential role in the treatment of AHNP.
Objective To examine the role of recombinant interleukin-10 (IL-10) and the therapeutic effect of endotoxin-induced uveitis (EIU) in rats.Methods Fifty-six male Wistar rats were randomized into three groups. IL-10 treatment group and positive control group had 24 rats respectively, and the normal control group had eight rats. Endotoxin-induced uveitis (EIU) is an established animal model of acute ocular inflammation induced by LPS intravenous injection (1 mu;g/kg). The onset times and signs were observed and the clinical scores were recorded. The blood samples and the aqueous humor samples of right eye were collected separately before the rats were sacrificed at fourth hour, 24th hour and third day after LPS injection. The enzyme-linked immunosorbent assay was used to measure tumor necrosis factor (TNF) alpha;,IL-6, and IL-10 levels in the serum and aqueous humor. The left eyes were used for pathological examination and pathological grading. Results The symptoms of uveitis were appeared in all 24 rats in the positive group. The average onset time was (3.81plusmn;1.05) hours, the average clinical score was 3.67plusmn;1.97. The mild manifestations of uveitis were also appeared in all of the rats in treatment group. The average onset time was (5.63plusmn;1.02) hours, the average clinical score was 2.00plusmn;1.25. The average onset time in treatment group was postponed compared with the rats of positive group (t=4.95, P=0.000). The clinical scores (t=3.50, P=0.00) and the pathological grades (t=3.28, P=0.00) in treatment group were lower than those of positive group. There were not signs or pathologic changes in all the eight rats in the negative control group. The serum and aqueous humor levels of TNF-alpha; and IL-6 in the rats of positive group were higher than those of the treatment group and control group (F=15.34, 57.65, 67.59, 8.42; P=0.00). The serum and aqueous humor levels of IL-10 in the rats of treatment group were higher than those of the positive group and the control group (F=17.84,7.76; P=0.00). There were positive correlations between the level of aqueous humor TNF-alpha;, serum and aqueous humor levels of IL-6 and the disease severity (reye＝0.58, 0.31,0.81, rpath＝0.56, 0.31, 0.74; P＜0.05). The negative correlations were presented between the serum levels of IL-10 with the disease severity (r=-0.54,-0.55; P=0.00). There were negative correlations between the serum and aqueous humor levels of TNF-alpha; and IL-6 and the onset time of the disease (r＝-0.47,-0.59,-0.77,-0.36; P＜0.05) as well. Conclusions These findings bly suggest that suppressive IL-10 is a potent candidate for the prevention of TNF-alpha; and IL-6 in uveitis and could be applied as a novel immunoregulatory agent to control EIU.
Objective To investigate the effect of recombinant human growth hormone (rhGH) on intestinal bacteria and endotoxin translocation in experimental obstructive jaundice. MethodsObstructive jaundice rat models were made and divided into three groups: sham operation (SO) group, obstructive jaundice (OJ) group and obstructive with rhGH (OG) group. The number in each group was 20. The mice in rhGH group underwent subcutaneous injection each day of Saizen, with the dose of 0.75 u/kg, while SO group and OJ group received nitric sodium injection. All these maitained for 2 weeks, then the animals were killed and the endotoxin were determined by limulus test, and bacterial cultures of ascites, blood, mesenchymal lymph node, kidney, spleen and liver were made, and the height of villi and the thickness of intestinal walls were examined.ResultsThe value of endotoxin in OJ group was (0.77±0.03) u/ml, higher than that in OG group and SO group, while it was (0.40±0.02) u/ml and (0.33±0.03) u/ml (Plt;0.01). The bacteria translocation rate in OJ group was 58.8%, much higher than that in OG group, which was 10.0% (Plt;0.01). There was no difference between OG group and SO group (Pgt;0.05). Villi height in OJ group was (183.39±11.09) μm, and thickness was (255.62±16.58) μm. While in OG group was (237.52±13.65) μm, and (320.81±14.34) μm (Plt;0.01) respectively.Conclusion rhGH has significant effect on protecting the injuried mucosa barrier in obstructive jaundice, and can decrease endotoxemia and bacteria translocation.
Objective To study endotoxin release induced by differential antibiotics in gram negative bacterial infection. Methods Thirty critical patients accompanied with gram negative bacterial infection were divided into group A (imipenem group, n=15) and group B (ceftazidine group, n=15). Imipenem (0.5 g iv q8h) and ceftazidine (1.0 g iv q8h) were given respectively. White blood cell (WBC), systolic blood pressure (SBP), lipopoly sacchride (LPS), tumor necrosis factor alpha (TNFα) and high density lipoprotein (HDL) were determined in 0, 1, 2, 3, 5 and 7 day. Results There was no difference in the change of WBC between two groups. Group A had a more stable SBP than group B. There was lower endotoxin release in group A than in group B and so were the cytokines release. HDL level was lower in group B than in group A. Conclusion Imipenem has lower endotoxinliberating potential than ceftazidine and mediate lower cytokines release. HDL may protect the patients from LPS damage.
In this article, the first time use of continuous veno-venous hemofiltration(CVVH) combined with toxic absorption for the treatment of a crush syndrome patient injured in earthquake is described. Correct therapeutic regimen, close observation and prescription condition are crucial for the success of management. The evidence for the application of this method is also discussed in detail.
ObjectiveTo explore the effect of endotoxin on insulin secretion from islet βcell of rat pancreas.MethodsAfter the model of endotoxemia was established in rats with intraperitoneal injection of LPS (2 mg/kg),the changes of insulin level in the serum and pancreas were dynamically determined, the expression of inducible nitric oxide synthase (iNOS) by situ hybridization and DNA damage in islet cells were also observed, the effect of sodium nitroprusside (exogenous NO) on synthesis and secretion of insulin from isolated islet βcell of normal rat pancreas under high glucose stimulation was also evaluated.ResultsThe level of glucose and insulin in plasma were significantly increased at 12th and 6th h, respectively and kept on 3 d after injection of LPS,but the insulin level in pancreas was not remarkably altered.The expression of iNOS and DNA damaged significantly enhanced at 6 d after endotoxemia. The high glucosestimulated insulin synthesis and secretion were bly inhibited by exogenous NO.ConclusionThese findings suggest that LPS be stimulate the expression of iNOS and NO product,which inhibites synthesis and secretion of insulin in islet βcells,but it stimulates insulin secretion by another mechanism,and results in dysfunction and destruction of the rat pancreas.
Objective To investigate the protective effects of endotoxin pretreatment on lung injury of rats with endotoxemia. Methods The rat model of acute endotoxemia was established by injecting lipopolysaccharide (LPS) intraperitoneally. Seventy-two male Wistar rats were randomly divided into three groups, ie. a saline control group (N, n=24) , a LPS-treated group (L, n=24) , and a LPS pretreated group ( P, n=24) . Each group was divided into 2 h, 4 h, 6 h, and 12 h subgroups. The rats in group P were firstly administered with introperitoneal injection of 0.25 mg/kg LPS. After 24 hours, they were subjected to the injection of 0.5 mg/kg LPS. The rats in group N and L received injection of equivalent amount of saline. After 72 hours, the rats in group L and P were challenged with intravenous injection of 10 mg/kg LPS, otherwise saline in group N. Six rats were killed at 2, 4, 6 and 12 hours respectively after injection of LPS in group L and P. The lungs were removed for detecting intercellular adhesion molecule-1 ( ICAM-1) , superoxide dismutase ( SOD) , and malondialdehyde (MDA) . Meanwhile the level of tumor necrosis factoralpha ( TNF-α) in serum was measured, and the pathological changes of lung were also examined. Results The contents of ICAM-1, MDA and TNF-α in the LPS-treated 4 h group were 75.07 ±0. 53, ( 3.93 ± 0.42) μmol/g, and (478.62 ±45.58) pg/mL respectively, significantly higher than those in the saline control group. The endotoxin pretreatment reduced the above indexes to 42.40 ±0.44, ( 2.89 ±0.49) μmol / g and ( 376.76 ±43.67) pg/mL respectively (Plt;0.05) . The content of SOD in the LPS-treated 4 h group was ( 6.26 ±0.31) U/mg, significantly lower than that in the saline control group. The endotoxin pretreatment increased SOD to ( 8.79 ±0.35) U/mg. Conclusion Endotoxin pretreatment can suppress the progress of lung injury in rats with endotoxemia and protect the lung tissue by down-regulating the inflammatory response and oxygen free radical production.
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, and is the leading cause of death in intensive care unit patients due to limited therapies currently. As is known to all, endotoxin is important in the pathogenesis of sepsis, whereby infection triggers a systemic inflammatory response, resulting in release of pro- and anti-inflammatory cytokines, which are thought to be responsible for the tissue damage that occurs in sepsis patients. Therefore, removing endotoxins is considered as an effective way to improve the conditions of sepsis patients. Both Toraymaxin (PMX) and adsorptive membrane such as oXiris can remove endotoxins by adsorption, and in this review we will summarize current studies, included in vitro study, animal study, and clinical research to show the benefit from endotoxin removal by oXiris, and also give some suggestions about oXiris clinical practice from experienced experts.
TO investigate the relationship between endotoxemia and structural change in the pancreatic tissue and therapeutic effects of naltrexone (NTX) on experimental acute hemorrhagic necrotizing pancreatitis in rats. The model of acute hemorrhagic necrotizing pancreatitis (AHNP) of rats was induced by retrograde injection of 5% sodium taurocholate into the pancreatic duct. One hundred and ten Wistar rats were randomly divided into three groups: control group (n=20),AHNP group (n=45) and NTX treatment (n=45) group. The weight of pancreas and plasma levels of amylase and endotoxin were measured as well as changes of the pancreatic histology were examined by light and electric microscope in 6h, 12h, 24h after operation. Results as compared with control groups , amylase and endotoxin in AHNP group were significantly higher in the plasma and the damage to pancreatic tissue was increased in severity as observed with light and electric microscopes in 6h, 12h, 24h after operation. Comparison between NTX treatment groups with AHNP groups demonstrated that amylase and endotoxin were significantly decreased in the plasma, and the damage to pancreatic tissue was reduced in NTX treatment phase. Conclusion these results showed that endotoxemia was induced by AHNP, but NTX decreased the edotoxin level in the plasma and improved the damage of pancreatic tissue. The lethality was significantly lowered and average survival time was prolonged during NTX treatment of AHNP.
