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Objective: To investigate the changes in the plasma levels of endotoxin in severe burn patients during administration of antibiotics., Methods: Fifty severe burn patients with burn area larger than 30% TBSA were enrolled in the study, and they were respectively treated with Netilmicin (A group), Cefoperazone (B group), Ceftazidime (C group) and Imipenem/Cilastatin (D group). Venous blood samples were harvested for determination of endotoxins levels before treatment and 1, 2, 3, 5, 7 post-treatment day (PTD)., Results: The plasma levels of endotoxin were elevated in different degrees in A, B and C groups. The plasma levels of endotoxin in B group were higher on 1, 2 PTD than on 3, 5, 7 PTD, and they were also higher than that in D group (P < 0.05). The plasma levels of endotoxin in C group reached the peak on 5 PTD [(0.398 +/- 0.172) EU/mL], which were higher than that before treatment [(0.251 +/- 0.142) EU/mL, P < 0.05] and other groups (P < 0.05). The plasma levels of endotoxin in D group were lower on 1, 2 PTD than that before treatment (P < 0.05)., Conclusion: Different amounts of endotoxins can be released after treatment with antibiotics in severe burn patients. Attention should be paid to the effect of antibiotics on the levels of endotoxin in practice.

Objective: To observe the effect of Gingerol on endotoxemia mouse induced by heatstroke., Methods: Forty mice were randomly divided into five groups, the endotoxemia model group (A), the normal temperature group (B), the Gingerol treated group (C), the solvent control group (D), and the saline control group (E), 8 mice in each group. Group B to E was administered with saline, Gingerol, solvent and saline respectively. Mice in group B were placed at room temperature 25 +/- 0.5 degrees C , relative humidity 43 +/- 5 % for 2 hrs, while mice in the other groups were exposed under 35 +/- 0.5 degrees C and relative humidity 65 +/- 5 % for 2 hrs in an artificial hot-climate mimic cabin to establish heatstroke endotoxemia model. The energy metabolic level of celiomacrophage was detected with MTT; the phagocytic ability was examined with neutral red chromometry; the hepatocyte ultrastructure was observed with transmission electron microscopy, as well as the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in plasma was tested., Results: As compared with Group A, D and E, in Group C, energy metabolic levels of macrophage, phagocytic ability, and activity of SOD were significantly higher (P < 0.01), and the level of MDA was significantly lower respectively (P < 0.01), with the levels of SOD and MDA approaching to those in Group B (P >0.05). The pathologic changes of hepatocyte ultrastructure in group C were less than those in the other three endotoxemia groups., Conclusion: Gingerol could raise the energy metabolic level of celio-macrophage to enhance its phagocytic ability, increase the activity of SOD and reduce the production of MDA in mouse with heatstroke endotoxemia, so as to alleviate the liver damage.

Objective: To investigate the role of PGE(2) and cAMP in the postburn change in granulopoiesis in bone marrow in burned mice with endotoxemia., Methods: One hundred and seventy eight mice were randomly divided into burn with LPS administration, simple burn, simple LPS administration and control (injection of normal saline) groups. The COX-2 expression and the contents of PGE(2) and cAMP in myeloid cells in injured mice in all groups were determined by RIA (radioimmuno-assay) within 1 postburn week and immunohistochemistry methods. At the same time the change in granulopoiesis was dynamically observed., Results: The granulopoiesis was enhanced slightly at the early stage of burn and with endotoxin challenge, followed by suppression. The COX-2 expression in myeloid cells the contents of PGE(2) on supernatant of marrow cells and intracellular cAMP in the myeloid cells was increased at 12 postburn hour (PBH) up to 5 postburn day (PBD). Furthermore, the change in the cAMP was evidently and positively correlated with that of PGE(2) (r = 0.978, P < 0.01), but was negatively correlated with that of CFU-GM (r = -0.971, P < 0.01), Conclusion: PGE(2) might play pivotal roles in the postburn granulopoiesis suppression in bone marrow during endotoxemia. This effect might be accomplished by its ligating to its special receptor and to activate adenylate cyclase so as to increase the intracellular content of cAMP in bone marrows.

Objective: To explore the influence of glutamine dipeptide on the plasma endotoxin levels in severely burned patients., Methods: Thirty burned patients with TBSA of 30 - 70% and III degree burn area more than 20% were randomly divided into control (C) and study (S) groups. Glutamine dipeptide powder in dose of 0.5 g/kg/day was given orally in bolus to those patients in S group during 1 - 12 postburn days (PBDs). The plasma levels of glutamine were determined during 1 - 12 PBDs. Simultaneously, the plasma endotoxin level was detected on 1, 3, 6 and 12 PBDs. The wound healing rate at 30 PBD and total hospital stay days were recorded., Results: The plasma glutamine levels at 1 PBD in C and S groups were obviously lower than normal level (659.5 +/- 35 micromol/L), but there was no difference between these two groups (P > 0.05). The plasma glutamine levels in C group was much lower than that in S group at 12 PBD (P < 0.05). The plasma endotoxin concentration on 1 PBD in these two groups increased evidently compared with the normal value (P < 0.05), and there was no difference between the two groups (P > 0.05). The plasma endotoxin level in S group was much lower than that in C group on 3 PBD (P < 0.05). As for the wound healing rate at 30 PBD, it was markedly higher in S group than that in C group (91% vs 85%). On the other hand, the hospital stay days in S group were evidently lower than that in C group (52 vs 67)., Conclusion: Oral intake of glutamine dipeptide in burn patients could be beneficial to the maintenance of the plasma concentration of glutamine and in decreasing plasma endotoxin level. It would also enhance the wound healing rate at 30 PBD and shorten the hospital stay days.

Objective: To explore the relationship between endotoxemia and the severity of disease condition and therapeutic effect., Methods: According to randomized controlled principle, the 153 acute infectious patients were divided into simple antibiotics treated group and antibiotics plus Chinese drugs combined treated group, and patients in each group were subdivided into 3 types according to acute physiology and chronic health evaluation (APACHE-III) scoring: type A (APACHE-III scoring < or = 20 points), type B (APACHE-III scoring 21-40 points) and type C (APACHE-III scoring > 40 points). The 77 cases in the simple treated group were 40 males and 37 females, aging 18-76 years, mean 46.5 +/- 27.5 years, 41 cases of type A, 28 of type B and 8 of type C, treatment course 10-14 days, mean 11.5 +/- 2.5 days. The 76 cases in the combined treated group were 39 males and 37 females, aging 18-70 years, mean 44.5 +/- 25.5 years, 37 of type A, 30 of type B and 9 of type C, treatment course 10-14 days, mean 10.5 +/- 2.5 days. Limulus test was used to determine the endotoxin content in peripheral blood of patients, and further analysis on the relationship between endotoxemia and APACHE-III scoring was conducted., Results: Acute severe infectious patients whose APACHE-III scoring > 20 points occurred endotoxemia (P < 0.05), and the condition of disease was positively related to the APACHE-III scoring (r = 0.718, P < 0.05). Chinese drugs plus antibiotics can obviously alleviate endotoxemia (P < 0.05) and improve the prognosis of patients., Conclusion: Endotoxemia can serve as a referential parameter for predicting the severity of disease. Integrated therapy of Chinese and western medicine in treating bacterial infection revealed better results than that of antibiotics solely.

Objective: To investigate the role and significance of PAF in the early pulmonary injury following burns combined with endotoxemia in rats., Methods: An animal model, in which rats were subjected to 20% TBSA III degree burns combined with intraperitoneal injection of lipopolysaccharide (LPS), was used for this experiment. The changes in the pulmonary morphology were observed by LM, EM and immunohistochemistry(IHC). The contents of PAF and TNF-alpha in the plasma were determined with quantitative analysis. PAF receptor antagonist(BN50739) was used to treat early pulmonary injury., Results: PAF was one of the inflammatory mediators to precede TNF changes during burns combined with endotoxemia in the early stage of pulmonary injury. The contents of PAF in the plasma was positively correlated to the extent of pulmonary injury, which may be alleviated after injection of PAF receptor antagonist (BN50739)., Conclusion: The results suggest that PAF plays an very important pathogenic role in the early lung injury resulted from burns combined with endotoxemia.

Objective: To investigate the dynamic changes in tumor necrosis factor-alpha(TNF-alpha) mRNA expression and the relationship between TNF-alpha mRNA and gut-derived endotoxemia in rats after thermal injury., Methods: 56 male Wistar rats were subjected to a 35% total body surface area full-thickness thermal injury and randomly divided into 3 groups: normal controls, 35% III* injury group, and polymyxin B treatment group. Plasma endotoxin was measured by limulus amebocyte lysate test, and tissue TNF-alpha mRNA expression was determined by reverse transcription polymerase chain reaction (RT-PCR)., Results: It was found that a significant elevation of endotoxin concentration in both portal and systemic circulation was observed at 2 hours after thermal injury, peaking at 8 hours (P < 0.05-0.01) and lowering at 24 hours. Meanwhile, TNF-alpha mRNA expression significantly increased in liver, lung, intestine, and kidney at 2 hours, peaking at 8 hours, and a high level was maintained till 24 hours. However, treatment with a low-dose polymyxin B could lower both portal and systemic endotoxin levels, and markedly inhibit TNF-alpha mRNA expression in various organs. In addition, a positive correlation between portal endotoxin concentration and pulmonary, intestinal and renal TNF-alpha mRNA expression was noted (r = 0.365-0.484, all P < 0.05)., Conclusion: This study suggests that major burns can lead to a marked elevation of tissue TNF-alpha mRNA expression in vital organs, which may be associated with gut-derived endotoxemia caused by acute thermal injury.

Objective: To observe the time course and tissue distribution of endotoxin, and to evaluate the potential role of local endotoxin in mediating multiple organ damage following burns., Methods: Wistar rats were subjected to a 35 percent full-thickness scald injury. They were grouped according to time of sacrifice: no burn, and 12, 24, 48, 72 hours postburn. Tissue specimens from liver, kidneys, lungs and intestine were aseptically harvested to determine tissue endotoxin levels. In addition, blood samples were obtained for measurement of organ function parameters., Results: It was found that endotoxin levels in liver, spleen and lungs increased markedly after thermal injury, with the highest level in liver. Meanwhile, serum GPT, GOT, CK-MB levels, and pulmonary myeloperoxidase(MPO) activities markedly elevated after scald injury, reaching a maximum between 12 and 24 hours. Intestinal diamine oxidase(DAO) activities tended to decrease at various time points postburn. In addition, there were highly positive correlations between pulmonary endotoxin levels and MPO activities, and also between renal endotoxin levels and serum Cr values., Conclusion: Burn injury per se can result in gut-derived endotoxin translocation which is mainly distributed to the liver, spleen and lungs. Endotoxin accumulated in local sites may play an important role in mediating multiple organ damage secondary to major burns.

Objective: To observe the distribution and cell localization of TNF-alpha mRNA and its protein and study their role on pathogenesis of liver injury in rats., Methods: An animal model in which rats were subjected to 20% TBSA III degree burns combined with intraperitoneal injection of lipopolysaccharide (LPS) was used for this experiment. The changes in the hepatic morphology, functions and TNF-alpha content in the serum and the expression, localization of liver TNF-alpha and TNF-alpha mRNA were determined with LM and EM, quantitative analysis, immunohistochemistry(IHC) and in situ hybridization (ISH)., Results: It was showed that there were sinusoid reaction, KCs activation and degeneration, necrosis of HCs, and platelets aggregation, fibrin deposition and PMNs attachment in sinusoid. The activity of ALT was obviously elevated and the content of ALB was slightly lowered. The contents of TNF-alpha in serum showed the peak values at 3 h. TNF-alpha was mainly localized in sinusoid endothelial cells(SECs), Kupffer cells (KCs) and TNF-alpha mRNA was mainly distributed in KCs, polymorphonuclear neutrophils (PMNs) and macrophages(MPs)., Conclusion: The results suggest that the expression and localization of TNF-alpha mRNA and its protein are in agreement with the pathological changes of liver injury. TNF-alpha is one of the key cytokines in pathogenesis of liver injury in rats after burns complicated by endotoxemia.

Objective: To investigate the effects of platelet activating factor (PAF) on the occurrence of enterogenic endotoxemia after burn., Methods: The relationship between changes of PAF and enterogenic endotoxima was observed on a model of rats with 30% TBSA III degree burn., Results: The intestinal permeability and plasma endotoxin were significantly elevated and were positively correlated with the increase of PAF in the intestinal tissue and blood. PAF antagonist treatment significantly decreased the intestinal permeability and the levels of plasma endotoxin. After intravenous injection of enogenous PAF to healthy rats, the intestinal permeability and plasma endotoxin were also markedly increased, which was significantly depended on the dose of PAF., Conclusion: PAF is one of the important factors for the occurrence of postburn enterogenic endotoximia.

The incidence of endotoxemia in 153 patients with different liver diseases was determined by Limulus Lysaite Test(LLT). Comparative studies were carried out on the levels of tumour necrosis factor-alpha(TNF-alpha) between positive and negative endotoxemia in patients suffering from chronic liver diseases. At the same time, 58 patients of positive endotoxemia were divided into two groups--bifidobiogen group (38 cases) and control group(20 cases). The patients in bifidobiogen group were treated mainly with daily administration of bifidobiogen for 1 month besides general liver--protection therapy and the bifidobiogen was not given to the control group. The results showed that: 1. Incidence of endotoxemia in 153 patients suffering from various types of liver diseases was 65.36%; the highest rate was found in the patients with severe hepatitis; 2. The TNF-alpha level was obviously increased in the patients of positive endotoxemia; 3. The total efficacy in bifidobiogen group was significantly higher than that in control group. The data suggest that chronic liver diseases are generally complicated with endotoxemia, and TNF-alpha plays an important role in the pathogenesis of endotoxemia. The serum endotoxin level may be reduced after the treatment with bifidobiogen.

To observe the effect of HSM (hypertonic saline/mannitol) on thymic cell apoptosis induced by endotoxin (LPS) in mice, twenty-four mice were divided into three groups (8 mice/each group): 1. Control group, each mouse was intraperitonealy injected with normal saline; 2. LPS group, each mouse was intraperitonealy injected with LPS; 3. LPS + HSM group, each mouse was intraperitonealy injected with HSM before and after injection of LPS. The results showed that the percentage of apoptosis of HSM + LPS group was lower than that of LPS group (P < 0.01); the ladder of nucleosomal DNA fragments by agarose gel eletrophoresis of HSM group was not typical as compared with that of LPS group. It is suggested that HSM might protect the apoptosis of mouse thymic cell induced by LPS and may improve the immune function.

Objective: To study the increasing sensitivity to endotoxin induced by hemorrhagic shock and its mechanism., Methods: Routine biochemical assay, reverse transcription-polymerase chain reaction. (RT-PCR) and cell in situ hybridization were used to investigate the effects of low-level endotoxin under hemorrhagic shock and its possible mechanism., Results: In rabbits, blood pressure levels were significantly decreased, and plasma lactate and beta-glucuronidase (beta-G) levels increased in hemorrhagic shock (HS) + LPS group, all of which were significantly different from those in the LPS or HS group. All of the animals in the HS + LPS group were dead while those in the LPS or HS group survived 24 hours after shock. The results of RT-PCR showed that expression of lipopolysaccharide-binding protein (LBP) mRNA in the liver, lungs and kidneys was increased in rats after shock and resuscitation. The expression of CD144 mRNA in the peritoneal macrophages in mice was also enhanced after hemorrhagic shock and subsequent resuscitation showed by cell in situ hybridization., Conclusion: Hemorrhagic shock can significantly increase the sensitivity to endotoxin possibly because of up-regulation of LBP/CD14 after shock.

Objective: Endotoxin as the inciting agent of cytokines and other mediators, whose high level expression correlates with the septic shock and MOF, has been the one of leading causes of death in ICU., Methods: For treating sepsis and MOF caused by endotoxin, the anti-lipid A of LPS antibody was used, 19 burned patients whose TBSA varied from 50% to 100% were divided into anti-LPS treatment group and nontreated group., Results: The levels of serum endotoxin, IL-6, IL-8, TNF and soluble IL-2R were lower obviously in patients of anti-LPS group than those of nontreated group (P < 0.05)., Conclusion: Clinical study surggests that anti-lipid A of LPS antibody can act as an therapeutic agent against gram-negative bacterin infection in burned patients.