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AIM:To investigate therapeutic effects of recombinant human growth hormone(rhGH) on rat sepsis and its possible mechanisms.METHODS:Mean arterial pressure (MAP), levels of plasma TNFα, IL-1β and endotoxin, leukocyte count and survival rate within 1 week were determined after E. coli injection among control group, sepsis group and sepsis+rhGH group.RESULTS:(1)rhGH diminished the decrease of MAP, reduced plasma endotoxin and TNFα levels and increased neutrophil ratio in total leukocytes in sepsis rat. rhGH increased survival rate within 1 week on sepsis rat. (2)No changes were found in IL-1β level among the three groups.CONCLUSION:rhGH showed desirable beneficial effects on rat sepsis, which may attribute to: improving circulatory function;maintaining intestinal mucosa barrier, attenuating bacteria/endotoxin translocation and inhibiting the production and release of TNFα. 相似文献
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D. Hoffman J. Amorim A. DeClue 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2018,32(1):208-216
Background
People with critical illness (CI) commonly develop various forms of immune dysfunction, however, there is limited information concerning immune dysfunction in dogs with CI.Hypothesis
The immune response in CI dogs differs from that of healthy dogs.Animals
Immunologic variables were compared between 14 dogs with CI, defined as APPLEfast score of >20 points, admitted to the University of Missouri Veterinary Health Center Small Animal Clinic Intensive Care Unit and healthy controls (n = 15).Methods
Cohort study evaluating constitutive and lipopolysaccharide (LPS)‐stimulated TNF‐α, IL‐6, and IL‐10 production, phagocytosis of opsonized E. coli and respiratory burst capacity after opsonized E. coli or phorbol 12‐myristate 13‐acetate (PMA) stimulation, peripheral blood lymphocyte phenotype, and monocyte expressions of HLA‐DR and TLR‐4.Results
Lipopolysaccharide‐stimulated leukocyte TNF‐α (median, Q1, Q3; CI, 49, 49, 120; control, 655, 446, 1174 pg/mL; P = < 0.001), IL‐6 (median, Q1, Q3; CI, 49, 49, 64; control, 100, 49, 166 pg/mL; P = 0.029), and IL‐10 (CI, 49, 49, 56; control, 96, 49, 203 pg/mL; P = 0.014) production and both E. coli (median, Q1, Q3; CI, 60.5, 43, 88.5; control, 86.6, 81, 89.2%; P = 0.047) and PMA (CI, 40, 11.7, 70; control, 93, 83, 97.6%; P = < 0.001)‐stimulated respiratory burst capacity significantly decreased in CI dogs. Percentage of monocytes expressing TLR‐4 greater in the CI dogs (median, Q1, Q3; CI, 46.9, 24.3, 64.2; control, 16.4, 9.4, 26.2%; P = 0.005).Conclusion
These findings suggest dogs with CI develop immune system alterations that result in reduced respiratory burst function and cytokine production despite upregulation of TLR‐4. 相似文献3.
AIM: To investigate whether the bacterial DNA participates in SIRS and its possible mechanism. METHODS: Escherichia coli genomic DNA (EC DNA) was extracted and purified from Escherichia coli 25922 by alkaline lysis method. Mortality of mice challenged with EC DNA and the changes of TNF-α and IL-6 in rat serum were observed. ANA-1 cells were cultured in vitro, after the cells were stimulated by different concentrations of EC DNA and LPS, the level of TNF-α and IL-6 in supernatant were tested. Meanwhile,expression of TLR9 and TLR4 on cell surface was measured. Activation of NF-JB was also observed. RESULTS: The lethal effect of EC DNA on mice with an obvious dose-effect relationship was observed. The death happened within 24 hours. Calf thymus DNA and DNase I-treated EC DNA did not lead to mice to die. The changes of serum TNF-α and IL-6 in rats induced by EC DNA and LPS were similar, but TNF-α peak level of EC DNA group appeared 1 hour earlier than that of LPS group. In vitro, large amount of TNF-α and IL-6 were released from ANA-1 cells stimulated by EC DNA. High expression of TLR9 and TLR4 was observed on surfaces of THP-1 cells. In particularly, LPS induced strong activation of NFκB. The results suggested other pathway possibly took part in the signal transduction inducea by EC DNA. CONCLUSION: EC DNA has the abilities to lead to death of mice, andinduces serum TNF- αand IL- 6 level to increase in rats and ANA- 1 cells to release cytokines in vitro. High expression of TLR9 and TLR4, strong activation of NF- κB may be its importantmolecular mechanism, but other pathway probably exists to play an important role. 相似文献
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K. Osterbur F.A. Mann K. Kuroki A. DeClue 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2014,28(4):1141-1151
Multiple organ dysfunction syndrome (MODS), defined as the presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention, is a cause of high morbidity and mortality in humans and animals. Many advances have been made in understanding the pathophysiology and treatment of this syndrome in human medicine, but much still is unknown. This comparative review will provide information regarding the history and pathophysiology of MODS in humans and discuss how MODS affects each major organ system in animals. 相似文献
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A.N.K. Floras M.K. Holowaychuk D. Bienzle A.M.E. Bersenas S. Sharif T. Harvey S.K. Nordone G.A. Wood 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2014,28(5):1447-1453
Background
Serum N‐terminal pro‐C‐natriuretic peptide (NT‐proCNP) concentration at hospital admission has sufficient sensitivity and specificity to differentiate naturally occurring sepsis from nonseptic systemic inflammatory response syndrome (SIRS). However, little is known about serum NT‐proCNP concentrations in dogs during the course of sepsis.Objective
To determine serum NT‐proCNP and cytokine kinetics in dogs with endotoxemia, a model of canine sepsis.Samples
Eighty canine serum samples.Methods
Eight healthy adult Beagles were randomized to receive Escherichia coli lipopolysaccharide (LPS, 5 μg/kg) or placebo (0.9% NaCl) as a single IV dose in a randomized crossover study. Serum collected at 0, 1, 2, 4, and 24 hours was stored at −80°C for batch analysis. Serum NT‐proCNP was measured by ELISA and 13 cytokines and chemokines by multiplex magnetic bead‐based assay.Results
Serum NT‐proCNP concentrations did not differ significantly between LPS‐ and placebo‐treated dogs at any time. When comparing serum cytokine concentrations, LPS‐treated dogs had higher interleukin‐6 (IL‐6), IL‐10, TNF‐α and KC‐like at 1, 2, and 4 hours; higher CCL2 at 1, 2, 4, and 24 hours; and higher IL‐8 and CXCL10 at 4 hours compared to placebo‐treated dogs. There were no differences in serum GM‐CSF, IFN‐γ, IL‐2, IL‐7, IL‐15 or IL‐18 between LPS‐ and placebo‐treated dogs.Conclusions and Clinical Importance
Serum NT‐proCNP concentration does not change significantly in response to LPS administration in healthy dogs. Certain serum cytokine and chemokine concentrations are significantly increased within 1–4 hours after LPS administration and warrant further investigation as tools for the detection and management of sepsis in dogs. 相似文献7.
AIM: To explore whether IL-1β inhibits the oligodendrocyte precursor cell (OPCs) differentiation and affects axonal myelination. METHODS: One-day-old SD rats were randomly divided into control group and LPS group (48 rats in each group). The rats in LPS group were intraperitoneally injected with 1 mg/kg LPS. The rats in control group were injected with an equal volume of PBS. The rats in each group were further divided into 3 h, 24 h, 3 d, 7 d, 14 d and 28 d subgroups after injection. The expression of IL-1β and IL-1R1 in the rat corpus callosum at 3 h, 24 h, 3 d, 7 d was determined by double immunofluorescence and Western blotting. The myelin basic protein(MBP) expression in the rat corpus callosum at 14 d, 28 d after injection was also measured. In vitro, primary OPCs culture was performed and divided into control group, 30 μg/L IL-1β group, 30 μg/L IL-1β+IL-1Ra group and 30 μg/L IL-1Ra group. The expression of MBP in the OPCs induced differentiation for 3 d was observed by double immunofluorescence and Western blotting. RESULTS: The expression of IL-1β and IL-1R1 in the rat corpus callosum at 3 h, 24 h, 3 d, 7 d after LPS injection was obviously increased and the expression of MBP in the rat corpus callosum at 14 d, 28 d in LPS group was obviously decreased compared with control group in vivo. The level of MBP was significantly decreased after IL-1β treatment for 3 d in vitro. However, IL-1Ra (IL-1R inhibitor) reversed the down-regulation of MBP expression. IL-1β inhibited the expression of p-ERK, ERK over-expression reversed the down-regulation of MBP expression compared with IL-1β group. CONCLUSION: IL-1β inhibits the differentiation of OPCs, which may be involved in ERK pathways, thus leading to axonal hypomyelination in the corpus callosum of septic neonatal rats. 相似文献
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AIM: To characterize the hemoperfusion of abdominal organs in the early stage of sepsis in mice. METHODS: Health male Kunming mice were used in the study (n=100). The techniques of 2D, M-mode and pulse-wave Doppler were applied to evaluate the systolic functions of the heart and the blood flow of abdominal aorta, right renal artery and portal vein before cecal ligation and puncture (CLP) as the baseline and at the time points of 12 h, 24 h, 36 h, 48 h and 60 h after CLP. The mice survived for 7 d were considered as survivals. All data were compared with the baseline values.RESULTS: The cardiac output of the CLP mice remained in normal or hyperdynamic levels in the early stage of sepsis. Compensatory responses of systolic functions were observed. The levels of blood flow in abdominal aorta were increased first and then decreased. Resistent index (RI) and pulsatility index (PI) of abdominal aorta began to increase at the time point of 24 h. Blood flow of right renal artery showed a significant decline from the beginning to the end of our observation. No significant difference of the right arteriorenal RI and PI was observed. Portal venous flow increased significantly at 12 h, and decreased at 24 h after CLP. Congestion index of the portal vein was distinctly increased from 12 h to the end of the observation. CONCLUSION: The hemodynamics of abdominal organs in early stage of septic mice shows specific changes, indicating an important role in evaluating the mechanism of sepsis. 相似文献
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Hollis AR Furr MO Magdesian KG Axon JE Ludlow V Boston RC Corley KT 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2008,22(5):1223-1227
Reasons for Performing Study: Critical illness is associated with hyperglycemia in humans, and a greater degree and duration of hyperglycemia is associated with nonsurvival. Hypoglycemia is also seen in critically ill humans, and is associated with nonsurvival. This might also be true in the critically ill foal.
Objectives: To investigate the association of blood glucose concentrations with survival, sepsis, and the systemic inflammatory response syndrome (SIRS).
Methods: Blood glucose concentrations at admission (515 foals) and 24 hours (159 foals), 36 hours (95), 48 hours (82), and 60 hours (45) after admission were analyzed. Logistic regression analyses were performed to investigate the association of glucose concentrations with survival, sepsis, a positive blood culture, or SIRS.
Results: 29.1% of foals had blood glucose concentrations within the reference range (76–131 mg/dL) at admission, 36.5% were hyperglycemic, and 34.4% were hypoglycaemic. Foals that did not survive to hospital discharge had lower mean blood glucose concentrations at admission, as well as higher maximum and lower minimum blood glucose concentrations in the 1st 24 hours of hospitalization, and higher blood glucose at 24 and 36 hours. Foals with blood glucose concentrations <2.8 mmol/L (50 mg/dL) or >10 mmol/L (180 mg/dL) at admission were less likely to survive. Hypoglycemia at admission was associated with sepsis, a positive blood culture, and SIRS.
Conclusions and Potential Relevance: Derangements of blood glucose concentration are common in critically ill foals. Controlling blood glucose concentrations may therefore be beneficial in the critically ill neonatal foal, and this warrants further investigation. 相似文献
Objectives: To investigate the association of blood glucose concentrations with survival, sepsis, and the systemic inflammatory response syndrome (SIRS).
Methods: Blood glucose concentrations at admission (515 foals) and 24 hours (159 foals), 36 hours (95), 48 hours (82), and 60 hours (45) after admission were analyzed. Logistic regression analyses were performed to investigate the association of glucose concentrations with survival, sepsis, a positive blood culture, or SIRS.
Results: 29.1% of foals had blood glucose concentrations within the reference range (76–131 mg/dL) at admission, 36.5% were hyperglycemic, and 34.4% were hypoglycaemic. Foals that did not survive to hospital discharge had lower mean blood glucose concentrations at admission, as well as higher maximum and lower minimum blood glucose concentrations in the 1st 24 hours of hospitalization, and higher blood glucose at 24 and 36 hours. Foals with blood glucose concentrations <2.8 mmol/L (50 mg/dL) or >10 mmol/L (180 mg/dL) at admission were less likely to survive. Hypoglycemia at admission was associated with sepsis, a positive blood culture, and SIRS.
Conclusions and Potential Relevance: Derangements of blood glucose concentration are common in critically ill foals. Controlling blood glucose concentrations may therefore be beneficial in the critically ill neonatal foal, and this warrants further investigation. 相似文献