These studies established a macaque model of early-phase endotoxic shock, and investigated the resuscitation effects of three different solutions. Twenty-four macaques were assigned to four groups. Nineteen animals were given an intravenous dose of 2.8 mg/kg lipopolysaccharide (LPS). At 60 min after LPS challenge, the animals were given (i) 5 mL/kg normal saline (Ns group, n=6), (ii) 5% of 5 mL/kg sodium bicarbonate (Sb group, n=6), (iii) hypertonic 3.5% sodium chloride of 5 mL/kg (Hs group, n=7). The control group (Co group, n=5) was first injected with 1 mL/kg Ns and with 5 mL/kg Ns 60 min later. Haemodynamic parameters and blood gases were measured during the experiment, and myocardial morphology was examined on termination of the experiment. Administration of LPS caused hypotension and decreases of the left ventricular work index (LVWI). In the Sb group, mean arterial pressure, cardiac index, systemic vascular resistance index, LVWI and right ventricular work index were significantly higher than those of the Ns group. Pathological changes of myocardium were identified in all of the LPS groups. The studies suggest that macaques are suitable models for studying endotoxic shock and potential fluid therapies.
Background: The use of hypertonic crystalloid solutions, including sodium chloride and bicarbonate, for treating severe sepsis has been much debated in previous investigations. We have investigated the effects of three crystalloid solutions on fluid resuscitation in severe sepsis patients with hypotension.
TLR4 is the target of endotoxic tolerance induction. The induction of cross-tolerance of TLR2 following LPS challenge is present in vivo with endotoxin tolerance.
Objective
Chronic HBV infection can lead to “immune tolerance” in asymptomatic carriers (ACs), “immune injury” in active chronic hepatitis (ACH) patients or “immune abnormality” in cirrhosis (Cir) and hepatocellular carcinoma (HCC) patients. Previous investigations reported that chronic hepatitis presented abnormal expression of costimulatory molecules. We investigated the costimulation profile in the liver of ACs and patients with ACH, Cir and HCC.Methods
Patients with ACH, Cir and HCC, ACs and normal controls were recruited into the present study. The costimulation profiles and cytokines in the liver of patients were investigated by Western blotting, immunohistochemistry and real-time quantitative PCR. Correlations between serum alanime aminotransferase (ALT) levels, necroinflammation scores, cytokines and costimulatory proteins were assessed.ResultsThe ACs presented decreased inflammatory and increased inhibitory costimulation, which was negatively correlated with inflammatory costimulatory proteins and ALT, whereas the ACH patients exhibited increased inflammatory costimulation and decreased inhibitory costimulation, which was correlated with increased ALT. The Cir patients showed both increased inhibitory and inflammatory costimulation. The HCC patients exhibited both decreased inhibitory and inflammatory costimulation.ConclusionCostimulation participates in intrahepatic immune responses, and plays important roles in immune tolerance, immune injury and immune abnormalities in patients with chronic HBV infection.Electronic supplementary materialThe online version of this article (doi:10.1007/s00011-013-0691-3) contains supplementary material, which is available to authorized users.
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