Effect of nicotinamide mononucleotide on mortality of mice with endotoxic shock / 药学实践杂志

Objective To study the effect of nicotinamide mononucleotide (NMN) on the mortality of the lipopoly-saccharide (LPS)-induced endotoxic shock mouse model. Methods 10-week-old C57BL/6J male mice were randomly divided into groups, and were injected intraperitoneally (i.p.) with LPS (10 mg/kg) to induce endotoxic shock models. NMN was i.p. injected in three ways: (1) 0.5 h after modeling, doses of 10, 30, 100 and 300 mg/kg; (2) 0.5 h before modeling, doses of 30, 100, 300 and 600 mg/kg; or (3) 0.5 and 12 h after modeling, dose of 300 mg/kg each time. The death times of each group were recorded, and the survival curves were drawn. Results Compared with the solvent control group, NMN at different doses given 0.5 h after or before modeling didn’t improve the survival rate or delay the death time of endotoxic shock mice; But when given at 0.5 and 12 h 300 mg/kg after modeling, NMN accelerated the death of mice and increased the mortality of mice. NMN products by two manufacturers showed similar effects. Conclusion NMN has no therapeutic effect on LPS-induced endotoxic shock, and repeated administration of NMN after endotoxic shock will increase the mortality.

Effects of curcumin on acute kidney injury in endotoxic shock rabbits / 临床麻醉学杂志

Objective To investigate the effects of curcumin on acute kidney injury in endotoxic shock rabbits and discuss the possible mechanism.Methods Forty healthy male New Zealand white rabbits aged 2 months were randomly divided into 4 groups:control group (group C),curcumin control group (group Cur,curcumin 50 mg/kg),endotoxic shock group (group L,LPS 5 mg/ kg) and curcumin pretreatment group (group CurL,curcumin 50 mg/kg,LPS 5 mg/kg 30 minutes later),10 in each group.The concentrations of blood urea nitrogen (BUN) and creatinine (Cr) were detected,and the rabbits were sacrificed 6 h after LPS treatment.The pathological changes of renal tissue were examined and the pathological scores were recorded.SOD activities were measured by xanthine oxidase method.MDA contents were assayed according to thiobarbituric acid method.Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate the mRNA levels of Nrf2 and HO 1.The expressions of Nrf2 total protein,Nrf2 nuclear protein and HO-1 protein in the renal tissue were determined by Western blot.Results No abnormal structures were visible in groups C and Cur.The histopathological changes of the kidneys included glomerular shrinkage,cellu lar swelling,vacuolization and desquamation in tubules,interstitial edema and massive inflammatory cells infiltration in group L.Compared with group C,the pathological manifestations was relieved obviously in group CurL.Compared with group C,the pathological score,the concentrations of BUN,Cr,and MDA were obviously increased,while SOD activity was significantly decreased,the mRNA expression of Nrf2 and HO-1,the protein levels of Nrf2 total,Nrf2 nuclear and HO-1 in the renal tissues were distinctly increased in groups L and CurL (P＜0.05).Compared with group L,the pathological score,the concentrations of BUN,Cr and MDA were obviously decreased,while SOD activity was significantly increased,the mRNA expression of Nrf2 and HO 1,the protein levels of Nrf2 total,Nrf2 nuclear and HO-1 in the renal tissues were significantly increased in group CurL (P ＜0.05).Conclusion Curcumin can ameliorate acute kidney injury induced by endotoxic shock in rabbits,and its mechanism may be relate to activation of Nrf2/HO-1 signaling pathway.

Changes of small intestine villus and sublingual microcirculation in rabbits during endotoxic shock observed by sidestream dark-field imaging / 中国病理生理杂志

AIM: To investigate the changes of small intestine villus and sublingual microcirculation perfusion in the rabbits during endotoxic shock by sidestream dark-field imaging (SDF) after resuscitation to a mean arterial pressure (MAP) level.METHODS: New Zealand white rabbits (n=60) were randomly divided into 2 groups (group of villus and group of sublingua).The fistula operation of ileum was performed.Lipopolysaccharide was injected to establish endotoxic shock model, and fluid resuscitation (lactated Ringer's solution, 30 mL·kg-1·h-1) was given to maitain the MAP of the animals to 80 mmHg.Continuous norepinephrine was intravenously injected at 0.5~1 μg·kg-1·min-1 only if fluid therapy did not maintain the MAP level.The changes of microcirculatory perfusion indexes in small intestine villus and sublingual tissues such as vessels per villus (VV), microvascular flow index (MFI), proportion of perfused villi (PPVi), villus border score, villus vessel score, total vessel density (TVD), perfused vessel density (PVD) and proportion of perfused vessels (PPVe) were continuously observed and recorded by SDF before shock, during shock and after fluid resuscitation.RESULTS: MFI and PPVi in small intestine villus, and MFI, PPVe, TVD and PVD in sublingual tissues were significantly decreased after shock (P<0.01).Compared with MFI in sublingual microcirculation, MFI in villus was significantly decreased (P<0.01).MFI and PPVi in small intestine villus, and MFI, PPVe, TVD and PVD in sublingual tissues were improved after recovered to the target MAP by fluid resuscitation (P<0.05).However, MFI in small intestine villus was significantly lower than that in sublingual tissues after fluid resuscitation (P<0.01).CONCLUSION: The difference between small intestine villus and sublingual microcirculation perfusion during endotoxic shock is observed.The descent degree of microcirculation perfusion in small intestine villus is larger than that in sublingual tissues after shock, and the recovery degree of small intestine villus microcirculation is lower than that of sublingual microcirculation afer fluid resuscitation.

Changes of small intestinal villi microcirculation in sidestream dark-field imaging with different target blood pressure in rabbits during endotoxin shock / 中华危重病急救医学

Objective Changes of small intestine villus microcirculation perfusion in sidestream dark-field (SDF) imaging in the rabbits during endotoxic shock after fluid resuscitation with different target mean arterial pressure (MAP), and evaluation of feasibility of monitoring small intestine villus microcirculation by SDF were studied. Methods Sixty standard New Zealand white rabbits were randomly divided into two groups: low target MAP group (group A, n = 30) and high target MAP group (group B,n = 30). Fistula operation of ileum was madein vitro, and lipopolysaccharide (LPS, 2 mg/kg) was injected to establish endotoxic shock model. Group A was administered with the lower dose fluid resuscitation (lactated Ringer solution, 20 mL·kg-1·h-1) for target MAP of 65 mmHg (1 mmHg =0.133 kPa); group B was administered with the higher dose fluid resuscitation (lactated Ringer solution, 30 mL·kg-1·h-1) for MAP of 80 mmHg. Continuous norepinephrine intravenous injection (0.5-1.0μg·kg-1·min-1) was administered only after fluid therapy couldn't reach the target MAP. The changes of small intestine villus microcirculation perfusion indexes such as vessels per villus (VV), proportion of perfused villi (PPV), microvascular flow index (MFI), borders of villus score (BVS), vessels villus score (VVS) were continuously observed and recorded before the shock, during the shock and after fluid resuscitation using SDF imaging. The differences of microcirculation perfusion were compared between two groups using the specific parameter evaluation system to determine severity of villi microcirculation and injury scores at different stages.Results VV and borders of villus were clear and contact before shock in two groups. After shock, VV, PPV were significantly decreased in both two groups, the borders of villus were destroyed, MFI, BVS, VVS and the total score of villi injury microcirculation were obviously and severely decreased. Partial blood flow of villous capillaries after fluid resuscitation was recovered in two groups, but the perfusion of some region was un-balanced with the outworn borders of villus. VV were rose as compared before and after fluid resuscitation in groups A and B (vessels: 1.21±0.22 vs. 0.81±0.12, 1.54±0.28 vs. 0.79±0.13), and PPV [(31±4)% vs. (12±2)%, (38±5)% vs. (13±3)%], MFI (1.55±0.09 vs. 1.09±0.03, 1.97±0.11 vs. 1.05±0.03), VVS (points: 1.22±0.08 vs. 0.89±0.02, 2.06±0.15 vs. 0.90±0.02) and the sum of MFI, BVS, VVS (3.70±0.19 vs. 2.85±0.07, 5.01±0.29 vs. 2.88±0.08) were significant rose (allP 0.05).Conclusions For the small intestine villus microcirculation perfusion, the higher target MAP (80 mmHg) after fluid resuscitation or/and vasoconstrictor drugs usage were probably better than the relatively lower target MAP (65 mmHg) during endotoxic shock. SDF imaging is a very promising technique for intestinal villi microcirculatory visualization and assessment.

Protective Effect of Shenxi Dan on Multiple Organ Damage of Rats with Endotoxic Shock / 广州中医药大学学报

Objective To investigate the protective effect of Shenxi Dan,a recipe for cooling blood,activating blood and inducing resuscitation,on multiple organ damage of rats with endotoxic shock.Methods The SD rats were randomly divided into normal group,model group and Shenxi Dan group.Except for the normal group,the rats in the other groups were given intraperitoneal injection of D-galactosamine (GalN) and intravenous injection of lipopolysaccharide (LPS) to induce endotoxic shock.The changes in mean arterial pressure (MAP) during the entire process were monitored.Serum samples and liver and lung tissues were collected after infusion for 0 h,2 h,6 h,respectively,and then the amount of whole blood cells,serum contents of total bilirubin (TB),lactate dehydrogenase (LDH),aspartate aminotransferase (AST),and alanine aminotransferase (ALT) were detected.Meanwhile,the pathological changes in lung and liver tissues after hematoxylin-eosin (HE) staining were observed under light microscope.Results Compared with the model group,the decrease degree of the blood pressure was mild,platelet count(plt) was not decreased obviously,while the increase of serum TB,LDH,AST,ALT contents was significantly inferior,and inflammatory pathological changes of lung and liver tissues significantly were much relieved in Shenxi Dan group.Conclusion Shenxi Dan can improve lung and liver function of endotoxic shock rats,reduce the pathological damage,and improve microcirculation,which is helpful to clinical treatment of endotoxic shock.

Protective effects of oxymatrine injection on renal function of rats with endotoxic shock / 天津医药

Objective To evaluate the protective effects of oxymatrine injection on rats with endotoxic shock. Methods Wistar rat model of endotoxic shock was produced in this study. Twenty-four Wistar rats were randomly divided into normal control group (n=8), endotoxic shock group (n=8) and oxymatrine injection treatment group (n=8). Fifteen min?utes after the infusion of LPS (15 mg/kg) from femoral vein, oxymatrine was injected from femoral vein in treatment group, then we observed the mean arterial pressure (MAP) for six hours. At the end of experiment blood samples were harvested for measurement of urea and creatinine (Cr), which reflect renal function. Also contents of IL-6, IL-10, TNF-αin the renal ho?mogenate were detected. Results Oxymatrine can prevent progressive decrease of MAP in endotoxin shock treatment group. The contents of plasma urea and Cr were significantly higher in endotoxin shock group than those of control group. The contents of IL-6, IL-10 and TNF-αin renal homogenate increased obviously, but after the injection of oxymatrine, the contents of urea and Cr significantly decreased in treatment group, also IL-6 and TNF-α were significantly declined. Conclusion Oxymatrine provides protection at renal function after endotoxin shock, and its mechanism may be related to inhibit the releasing of inflammatory cytokines in kidney.

Expression of inositol 1,4,5-triphosphate receptor type Ⅰ in the myocardial tissue of rats with endotoxic shock / 中国小儿急救医学

Objective To investigate the changes of inositol 1,4,5-triphosphate receptor typeⅠ(IP3RⅠ)expression in the myocardial tissue of rats with endotoxic shock and probe the possible mechanisms of myocardial depression.Methods Thirty-three male Wistar rats were divided into four groups:control group (n=6) were injected normal saline(4ml/kg),and the other 3 groups (n=9) were injected endotoxin via femoral vein with a different dose of 10mg/kg,5mg/kg,and the artificial sacrificed group(10mg/kg,the rats were sacrificed when the mean arterial pressure was first rapidly decreased,then gradually increased to the normal level).IP3RⅠexpression in the myocardial tissue of rats was detected by immunohistochemistry,Western blot and colloidal gold immunoelectron microscopy technique.Results IP3RⅠexpressions were increased significantly in each group of rats with endotoxic shock than in the control group (P<0.01),and most obviously enhanced in the the artificial sacrificed group.The expression of IP3RⅠwas related to the level of mean arterial pressure.Ectopic expression of IP3RⅠwas observed around the cell membrane of the cardiac myocytes.Conclusion (1)The expression of IP3RⅠenhances in the myocardial tissue of rats with endotoxic shock,and exists ectopic expression.(2) The expression of IP3RⅠwas related to the level of mean arterial pressure.(3) IP3RⅠ may be related to the cardiac contractility and involved in the regulation of mean arterial pressure.

Effects of Small Volume Resuscitation with Different Fluids on Lung of Rats Undergoing Endotoxic Shock / 中山大学学报(医学科学版)

[Objective]This study was designed to investigate the effects of small volume resuscitation with different fluids on the lung of endotoxie rats.[Methods]Thirty SD rats weighting 180-250 g were divided randomly into 5 groups(n=6):Group C[lipopolysaccharide(LPS)negative control group],Group E(LPS+4 mL/kg physiologic saline),Group HSS(LPS+4 mL/kg 75 g/L hypertonic saline solution),Group HES(LPS+4 mL/kg hydroxyethyl starch 130/0.4),Group HSH(LPS+4 mL/kg 75 g/L hypertonic sodium chloride hydroxyethyl starch 40).Resuscitation was administrated 30 min after LPS injected.Pathological examination and score were made under optical microscope.Dry/wet ratios were observed.Levels of total protein of bronchoalveolar lavage fluid(BALF)were measured.Thibabituric acid(TBA)was used to measure tissue malonaldehyde(MDA)levels.Xanthine oxidase(XO)was employed to measure the tissue activity of superoxide dismutase(SOD).[Results]Compared with group C,in the other 4 groups,pathological changes were server.Levels of total protein of BALF were higher(P＜0.05).Pathological score of group E was significantly higher(P＜0.01).Dry/wet ratio of group E was lower(P＜0.05).Tissue activity of SOD of group E was lower(P＜0.01).Levels of tissue MDA in group E and HSS were significantly higher.Compared with group E,in group HSS,HES and HSH,pathological changes were slighter(P＜0.01).Pathological scores and tissue MDA levels were lower(P＜0.01).Dry/wet ratios were higher(P＜0.05).Tissue activity of SOD were higher(P＜0.01),levels of total protein of BALF were lower(P＜0.05,P＜0.01).[Conclusion]Small volume resuscitation with HSS,HES,and HSH had protective effects on the lung of endotoxie rats.HES and HSH had better effect on decreasing the capillary permeability of the lung of endotoxic rats lung compared with HSS.

Effects of vagus nerve stimulation on endotoxic shock in rabbits / 中华急诊医学杂志

Objective To study the effects of electrical stimulation of efferent vagus nerve on the endotoxic shock in rabbits. Method Sixteen Newzealand rabbits were randomly divided into 2 groups, namely group S as the stimulation group and group C as the control group). Rabbits were subjected to bilateral cervical vagotomy and had challenge with intravenous injection of lipopolysaccharide (LPS) (E. COLI O111: B4 , DIFCO, USA) in a dose of 600 μg/kg. The distal end of the left vagus nerve trunk was connected to an electric stimulator with bipolar electrode and controlled by an acquisition system. Stimuli with stable voltage (10 V,5 Hz,5 ms) were applied twice to the nerve for 10 minutes just before and after the administration of LPS in group S. At the time before and after the infusion of LPS 30 min,60 min, 120 min, 180 min,240 min and 300 min respectively, the heart rate(HR)and the mean arterial blood pressure (MABP) in each animal were recorded, and blood samples were taken for measuring serum tumor necrosis factor-αa(TNF-α) and interleukin-10 (IL-10). Results Compared with group C,the electrical stimulation of efferent vagus nerve could significantly attenuated the LPS-induced hypotension and de-creased the contents of TNF-α[(38.12±7.85) pg/mL vs. (55.12±7.89) pg/mL, P <0.01], but increased the contents of IL-10[(55.12±9.37)pg/mL vs. (40.15±5.44) pg/mL, P <0.01]afar LPS challenge. Conclusions The stimulation of the efferent vagus nerve can down-regulate systemic TNF-α, production and attenu-ate the development of shock after LPS challenge.

Protection of vasoactive intestinal peptide on lung injury induced by endotoxic shock in rats / 中华急诊医学杂志

Objective To investigate the effects, and possible mechanism of action, of vasoactive intestinal peptide (VIP) on acute lung injury in a rodent model of endotoxic shock. Method Endotoxic shock was induced in Sprague-Dawley (SD) rats by intravenous injection of lipopolysacchaiide (LPS) at 10 mg/kg. Three groups (each group with 10 rats), were given injections of either normal saline (Control), LPS 10 mg/kg (LPS group), or LPS 10 mg/kg + VIP 5nmol (VIP). Samples were collected 6 hours after injection. Indices of lung injury including lung wet/dry weight ratio, protein concentration and neutrophil count in bronchoalveolar lavage fluid( BALF) were derived. Assays of TNF-α,IL-1β, IL-10 in serum and BALF were performed using ELISA. Light and electron microscopy were used to detect histopathological changes in lung tissues. Results The lung wet/dry weight ratio, protein concentration and neutrophil count in BALF were significantly raised in the LPS group compared to the Control group (P ＜ 0.05). These indices were significantly lowered in the VIP group compared to the LPS group, though not to the level of the control group. Concentrations of TNF-α, IL-1β, IL-10 in serum and BLAF also increased in the LPS group compared to the control group (P ＜ 0.0S). Levels of TNF-α and IL-1β were significantly lowered in the VTP group compared to the LPS group (P ＜ 0.05), while levels of IL-10 was significantly raised ( P ＜ 0.05). Histopathological changes due to lung injury were not as severe in the VIP group compared to the LPS group. CondusKms VIP plays a protective role during acute lung injury induced by endotoxic shock in rats. Its mechanism of action may be related to down-regulation of proinflammatory cytokines and up-regulation of anti inflammatory cytokines.

Effects of Xuebijing injection (血必净注射液) on hemodynamics of dogs with endotoxic shock / 中国中西医结合急救杂志

Objective: To investigate the influence of Xuebijing injection (血必净注射液) on hemodynamics of dogs with endotoxic shock and its mechanism. Methods: Endotoxic shock was induced by intravenous infusion of lipopolysaccharide of E.coli. O55:B5 to dogs, and the 24 dogs were randomly divided into control group and Xuebijing injection group. Xuebijing injection was administered in the Xuebijing injection group. The hemodynamic parameters and plasma lactate levels were monitored. Results: After the administration of endotoxin, the mean arterial pressure (MAP) decreased significantly, while the mean pulmonary artery pressure (MPAP) and cardiac index (CI) increased markedly in both groups (all P0.05). Moreover, plasma lactate level was lower in Xuebijing injection group than that in control group (P

Effect of platelet-derived growth factor and lysosomes of lung injury in macaque with early-phase endotoxic shock / 中华急诊医学杂志

Objective To study the effect of platelet-derived growth factor(PDGF)and lysosomes on lung injury in macaque with early-phase endotoxie shock.Method Eleven macaques were randomly divided into two groups,namely,control group(Co group,n=5)iand endotoxic group(En group,n=6).The macaque of the Co group injected with 1 ml/kg normal saline and the macque of the En group received a dose of 2.8 mg/kg Lipopolysaccharides(LPS)i.v.The blood gas was detected at 120 minutes after LPS challenging. Uhrastructure,cytochemistry of acid phosphatase(ACPase)detection by electronic microscopy and immunohistochemical assay of PDGF were completed in hmgs of all the macaque .Results Administration of LPS did not change the parameters of gas exchange,namely,PaO_2,PaO_2/Fi and PaCO_2.In the early phase,of endotoxic shock,ACPase activity products increased and lysosome destroyed in the alveolar cells.The pathologic changes of alveolus,such as degeneration of vessel endothelium,injury of alveolar epithelium and damage of basement membrane,and transudation of blood component were observed by electron microscopy in the En group. However,no pathological changes were found in the control group.By immunohistochemical staining,PDGF on alveolar wall in the En animals was observed,whereas no PDGF protein in the Co macaques was noticed. Conclusions Administration of LPS induced the expression of PDGF in the alveolar wall and lysosome injury in the alveolar cells,as a result of alveolar damage in early-phase endotoxin shock.In the meantime,the parameters of gas exchanges did not change.The PDGF may play an important role in the pathogenesis of lung during the early-phase of endotoxin shock.

Role of Nuclear Transcription Factor-KB in Endotoxin-induced Shock in Rats / 华中科技大学学报（医学）（英德文版）

To investigate the role of NF-κB in endotoxic shock in rats, the model of endotoxinshock rats was induced by intravenous infusion of lipopolysaccharide (LPS). 1 h, 2 h, 4 h and 6h after LPS injection, the activation of NF-κB in blood mononuclear cells and the content of TNF-α and IL-6 in plasma was detected by enzyme-linked immunoadsordent assay (ELISA). The level of mean arterial pressure (MAP) and the histopathological changes of lung and liver were also observed. The activation of NF-κB in mononuclear cells increased 1 h after LPS injection and reached its peak 2 h after the injection, and its level was higher than that of normal group. The level of TNF-α was increased 1 h after the infusion and peaked 2 h after the injection, and its level was higher than that of normal group after LPS infusion. The content of IL-6 increased gradually with time, the IL-6 level was higher than that of normal group after LPS injection. MAP was decreased gradually with time and its level was lower than that of normal group after LPS injection. Pathological examination showed that endotoxic shock could cause pulmonary alveolar hemorrhage, edema and infiltration of inflammatory cell in lung tissue and congestion, edema, capillary dilation and inflammatory cell infiltration in liver tissue. It is concluded that NF-κB can up-regulate the expression of TNF-α and IL-6 in plasma and play an important role in endotoxin-induced shock in rats.

An Experimental Study on the Protective Role of Aminoguanidine on Liver Injury in Endotoxic Shock / 中国普外基础与临床杂志

Objective To study the effects of aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS) on the pathological changes of liver tissues and ultrastructural changes of liver cells in rodent model of endotoxic shock. Methods Twenty-four male Wistar rats were randomly divided into normal control group,lipopolysaccharide (LPS) control group and AG treatment group, each group had 8 rats. Rats were challenged by E.coli LPS to set up the model of endotoxic shock, AG group were treated by aminoguanidine. The pathological and ultrastructural changes of liver tissues and plasma NO contents of three groups were observed and compared. Results Light microscopy revealed that many tiny abscesses scattered in liver tissue in LPS group, accompanied by necrosis of liver cells and neutrophils infiltration, while liver injuries of AG group were much slighter than that in LPS group. Electron microscopy revealed that there were dissolved plaques in hepatocyte nuclears, swelling of mitochondria, decreasing in number of mitochondrial ridges, while AG play a protective role to nuclears and mitochondria of hepatocytes. The plasma NO levels of LPS control group were higher than that of normal control group, and plasma NO levels decreased significantly after AG treatment, but still higher than that of normal control group. Conclusion Aminoguanidine selectively inhibits iNOS activity and prevents the overproduction of NO induced by iNOS, thus attenuates the damages of liver structure induced by NO. This method has potential value in clinical application, which deserves more deep research.

Effects of an Opiate Receptor Antagonist Naloxone on Endotoxic Shock and Tumorigenesis / 대한면역학회지

Septic shock is one of the leading cause of death in hospitalized patients and mortality rates of up to 50 % have been reported. Despite all efforts, no regimen today seems to be successful in the treatment of septic shock. The endogenous opioid system (EOS) includes three major families of peptides: dynorphins, endorphins and enkephalins. Several lines of evidence indicate that EOS is implicated in the pathophysiology of anaphylactic and endotoxic shock. An opioid receptor blocker naloxone has been used extensively in studies for the role of EOS or endogenous opiod peptides (EOP). However, there have been few, if any, detailed investigative studies regarding the effect of naloxone on TNF-a production and the lethality in response to endotoxin, and tumorigenesis. ...continue...

El factor de necrosis de los tumores o caquectina / Tumor Necrosis Factor (TNF) or Cachectin

Se presenta una revision de la literatura sobre el Factor de Necrosis de los Tumores o Caquectina, con base en articulos publicados durante los anos 1986-1987, haciendo hincapie en las diferencias funcionales y moleculares entre el FNT Alfa, la Linfotoxina o FNT Beta y la caquectina. Se enfatizan los mecanismos del shock, de la necrosis tumoral y de la caquexia; se indican las propiedades antitumorales del FNT in vivo e in vitro y se esbozan esquemas terapeuticos experimentales que permiten colegir que el FNT tendra un papel importante en la inmunoterapia del cancer en el hombre

This is a review of the 1986-1987 Literature on the Tumor Necrosis Factor (TNF) or Cachectin, emphasizing functional and molecular differences among TNF alpha, Iymphotoxin or TNF beta and Cachectin. Mechanisms of shock, tumor necrosis and cachexia are discussed. In vivo and in vitro antitumoral properties of TNF are indicated, as well as some experimental therapeutic regimens. These facts allow the suggestion that TNF might become an important aid for Immunotherapy of cancer in humans.

Effect of thyrotropin-releasing hormone (TRH) on endotoxic shock in rats / 中国药理学通报

The effect of TRH on endotoxic shock in rats was studied, iv 0. 22-2 mg ?kg-1 TRH significantly reversed hypotension induced by iv coli E. endotoxin (40 mg ?kg-1) into rats and caused a 4. 2 kPa rise in mean arterial pressure (MAP). MAP after TRH administered could be stablized over a higher level than control for 30 min and maintained for 3 h during observation. Interestingly enough, the MAP rose gradually in TRH-treated rats as contrast with increasingly falling of that in control group during the late shock. TRH also improved 24 h sur-vival of shock rats. The dose-response relationship could be observed between 0. 22 ~0. 67 mg ?kg-1 TRH and disappeared over a highest dose (2 mg ?kg-1). It was shown that the best dose to reverse hypotension and to improve survival was 0. 67 mg ?kg-1 TRH. Naloxone 2 mg ?kg-1 showed the nearly same effect as 0. 22 mg ?kg-1 TRH in increasing MAP, but the former had higher 24 h survival of rats than the later.

Acute lung injury induced by endotoxic shock and imbalance of Th1/Th2 type of cytokines / 重庆医科大学学报

Objective:To investigate the type of imbalance of cytokines and its relations to the ALI induced by endotoxic shock.Methods:ALI rats model was made by injcting lipopolysacharide(LPS) into jugular vein.Enzyme-linked immunosorbent assay(ELISA) was employed to measure interferon-?(IFN-?) level,interleukin-4(IL-4) level and the ratio of IFN-?/IL-4.Pathological examination was made under optical microscope at the same time.Results:Compared with normal control group,the IFN-? level,the ratio of IFN-?/IL-4 increased significantly(P0.05).Pathological examination of lung tissue proved the presence of ALI in rats.Conclusion:The imbalance of Th1/Th2 type cytokines exists in the endotoxic shock-induced ALI.

Changes of interleukin-18 mRNA in lipopolysaccharide induced monkey endotoxic shock / 中国免疫学杂志

Objective:To evaluate the levels of interleukin 18(IL-18) mRNA in peripheral blood mononuclear cells(PBMCs),livers and spleens in monkey endotoxic shock models.Methods:Cynomolgus monkeys were injected i.v. with lipopolysaccharide(LPS) (2.8 mg/kg) to prepare the endotoxic shock models. The mRNA levels of IL-18 in PBMCs,livers and spleens were tested by fluorescence semi-quantitative realtime reverse transcription(RT)-PCR and compared with that of TNF-? and IL-1?.Results:IL-18 mRNA expression in PBMCs remarkably increased at 120 min after LPS administration, so did in livers and in spleens at the same time. mRNA levels of TNF-? in PBMCs peaked at 60 min after LPS injection, and also increased markedly at 120 min in livers and spleens. IL-1? mRNA levels peaked at 60 min in PBMCs, and did not change so much in livers and in spleens.Conclusion:IL-18 mRNA expression in PBMCs can be up-regulated by LPS, but changed latterly than TNF-? and IL-1? in endotoxic shock cynomolgus monkeys. It is presumed that IL-18 can be produced by PBMCs and liver Kupffer cells(maybe splenic macrophages),and TNF-? is produced by a variety of cells, but IL-1? in bloodstream mainly come from PBMCs after LPS challenge.

The Simultaneous Observation of Microcirculation in Skin and Mesentery of Rats during Endotoxic Shock / 第二军医大学学报

Two types of laser Dopplcr microscopes and two sets of television-recording systems were applied to observe and compare the dynamic changes of microcirculation in skin and mesentery of rats during endotoxic shock. The results showed that blood flow disturbances was one of the common phenomena in microcirculation at the early course of shock. Spasm of arteriolcs and decrease of blood velocity in both areas were relatively same changes. However, the changes in diameter and exudation in venule showed great differences.