Lipopolysaccharide dose response in baboons.

A lipopolysaccharide (LPS) dose-response study in an experimental baboon endotoxemia model is presented to define the relevance of this model compared with human endotoxemia. We describe acute and subacute endotoxemic models in baboons, the first evoked by bolus injection of LPS (1 mg, 0.1 mg, or 4 ng per kg of Escherichia coli LPS), and the second evoked by infusion of 1.

[Endotoxin tolerance and hemorrhagic shock in rats].

The aim of the presents study was to investigate the protective capacity of endotoxin tolerance in a hemorrhagic shock model in rats. A pretreatment with low dose endotoxin induces a state of tolerance, which is characterized by decreased TNF alpha production in vivo and in vitro upon subsequent high dose endotoxin challenge. This endotoxin tolerance improves survival after hemorrhagic shock from 22.

[Transfusion of plasma of endotoxin tolerant rats improves survival of hemorrhagic shock in the rat model].

To evaluate the protective effect of endotoxin tolerant plasma after hemorrhagic shock, plasma of endotoxin tolerant animals was used for resuscitation of normal rats. The transfusion of plasma of endotoxin tolerant rats improved the survival rate from 20 to 60 per cent. In the sera of endotoxin tolerant animals a TNF inhibitory activity was detected, which could be transferred by the plasma.

S-nitroso human serum albumin treatment reduces ischemia/reperfusion injury in skeletal muscle via nitric oxide release.

Background: Peroxynitrite generated from nitric oxide (NO) and superoxide (O2-) contributes to ischemia/reperfusion (I/R) injury. Feedback inhibition of endothelial NO synthase by NO may inhibit O2- production generated also by endothelial NO synthase at diminished local L-arginine concentrations accompanying I/R.

Methods And Results: During hindlimb I/R (2.

Continuous venovenous hemofiltration improves arterial oxygenation in endotoxin-induced lung injury in pigs.

Background: Hypoxemia is common in septic acute lung failure. Therapy is mainly supportive, and most trials using specific inhibitors of key inflammatory mediators (ie., tumor necrosis factor alpha, interleukin 1) have failed to prove beneficial.

[Callus development after bored and unbored femoral interlocking nailing. An experimental study].

This was a prospective randomized baboon animal study, the study protocol was approved by the ethical committee according to the international guidelines for animal research projects. In 8 animals a midschaft femoral osteotomy was stabilized with reamed femoral interlocking nailing and in 8 animals by unreamed locked femoral nailing. Polychrome sequence bone labeling was done 5 weeks postop.

Procalcitonin release patterns in a baboon model of trauma and sepsis: relationship to cytokines and neopterin.

Objectives: Procalcitonin (PCT) has been described as an early, discriminating marker of bacteria-associated sepsis in patients. However, little is known of its source and actions, in part because no appropriate animal models have been available. We tested the hypothesis that plasma PCT increases during various pathophysiological conditions, such as hemorrhagic shock and sepsis, which differ with regard to the degree of associated endotoxemia.

Isolation, partial characterization, and concentration in experimental sepsis of baboon lipopolysaccharide-binding protein.

Lipopolysaccharide-binding protein (LBP) is important for mediating host responses to lipopolysaccharide (LPS). The structure and properties of human, rabbit, and murine LBP have been previously described. In this study we partially characterized baboon LBP and investigated its appearance in experimental sepsis.

4-Hydroxynonenal as a second messenger of free radicals and growth modifying factor.

Immunohistochemical analysis of the distribution of the lipid peroxidation product 4-hydroxynonenal (HNE) in the brain of baboons exposed to experimental hemorrhagic traumatic shock or sepsis showed that systemic oxidative stress and the thereby generated HNE affect the blood:brain barrier and the regulation of cerebral blood flow determining secondary brain damage. Similarly, HNE was determined during ischemia in the brain blood vessels of rats exposed to ischemia/reperfusion injury of the brain. After reperfusion, HNE disappeared from the blood vessels but remained in neurones and in glial cells.

Bacterial cell envelopes (ghosts) but not S-layers activate human endothelial cells (HUVECs) through sCD14 and LBP mechanism.

Bacterial cell-envelopes (called ghosts) and surface layers (S-layers) are discussed to be used as vaccines and/or adjuvants, consequently it is necessary to find out which immunomodulatory mediators are induced in human cells. The present work focuses on the effects of ghosts (Escherichia coli O26:B6), S-layers (Bacillus stearothermophilus) in comparison with LPS and antibiotic-inactivated whole bacteria (E. coli O26:B6) on human umbilical vein endothelial cells (HUVEC) with regard to the release of interleukin 6 (IL-6) and the expression of surface E-selectin and the role of lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and serum for this activation.

Anti-L-selectin antibody treatment of hemorrhagic-traumatic shock in baboons.

Objectives: The adhesion molecule L-selectin plays an important role in leukocyte-endothelium interactions, thereby contributing to inflammatory reactions. We tested the hypothesis that humanized anti-L-selectin antibodies reduce trauma-associated organ damage and mortality.

Design: Prospective, randomized experimental study.

Impaired energy metabolism in hearts of septic baboons: diminished activities of Complex I and Complex II of the mitochondrial respiratory chain.

Recent findings support the view that the bioenergetic part of septic organ failure is not caused by insufficient supply of oxygen but by disturbances of the mitochondrial function. Therefore, the aim of the present study was to investigate key enzymes of energy metabolism in septic hearts to answer the question whether or not impairment of mitochondrial or glycolytic enzymes occur under these conditions. For this purpose the well established model of septic baboons was used.

Intramedullary pressure and bone marrow fat extravasation in reamed and unreamed femoral nailing.

This study was designed to investigate whether intramedullary pressure and embolization of bone marrow fat are different in unreamed compared with conventional reamed femoral nailing in vivo. In a baboon model, the femoral shaft was stabilized with interlocking nailing after a midshaft osteotomy. Intramedullary pressure was measured in the distal femoral shaft fragment at the supracondylar region.

In vivo femoral intramedullary pressure during uncemented hip arthroplasty.

There is evidence in several animal and human studies that high intramedullary pressure in the femur is of causal significance for bone marrow release into the circulation, causing pulmonary fatty marrow embolization. A previous clinical study provided evidence that in uncemented hip arthroplasty, high intramedullary pressure and subsequent fat embolism with cardiorespiratory deterioration can occur. In this prospective clinical trial, the effect of five surgical techniques on the femoral intramedullary pressure was recorded intraoperatively in 36 patients during uncemented press fit hip arthroplasty.

Protective effect of bactericidal/permeability-increasing protein (rBPI21) in baboon sepsis is related to its antibacterial, not antiendotoxin, properties.

Objective And Summary Background Data: The recombinant fragment of bactericidal/permeability-increasing protein, rBPI21, has potent bactericidal activity against gram-negative bacteria as well as antiendotoxin (lipopolysaccharide [LPS]) action. On the basis of these activities, the authors sought to discover whether rBPI21 would be protective in baboons with live Escherichia coli-induced sepsis and whether the potential protective effects of rBPI21 (together with antibiotics) would be more closely related to its antibacterial or LPS-neutralizing effects.

Methods: In a prospective, randomized, placebo-controlled subchronic laboratory study, the efficacy of rBPI21 or placebo was studied over 72 hours in chronically instrumented male baboons infused with live E.

Anti-TNF treatment of baboons with sepsis reduces TNF-alpha, IL-6 and IL-8, but not the degree of complement activation.

The activation of complement and the release of TNF-alpha, IL-6 and IL-8 are important pathogenic factors behind organ dysfunction in sepsis. The aim of this study was to determine whether infusion of anti-TNF antibodies alters complement activation and plasma concentrations of pro-inflammatory cytokines at high doses of Escherichia coli. Six baboons received intravenously 2 x 10(9) live E.

Local and systemic reactions after lung contusion: an experimental study in the pig.

The present study was designed to investigate the consequences of isolated unilateral lung contusion on local alveolar and systemic inflammatory responses in an animal model in the pig. Isolated unilateral lung contusion was induced by bolt shot in eight mechanically ventilated animals under general anesthesia (sham: n=4). Plasma and bronchoalveolar lavage fluid were collected during a period of 8 h following lung contusion.

The inflammatory basis of trauma/shock-associated multiple organ failure.

Multiple alterations in inflammatory and immunologic function have been demonstrated in clinical and experimental situations after trauma and hemorrhage, in particular the activation of various humoral (e.g. complement, coagulation) and cellular systems (neutrophils, endothelial cells, macrophages).

Complementary DNA (cDNA) sequence of baboon tumor necrosis factor alpha.

Baboons are less LPS-sensitive than humans, even though their immune response mechanisms are similar. Since TNFalpha is a central mediator of the LPS-response we cloned and sequenced the baboon TNFalpha cDNA and compared the resulting sequence with the human TNFalpha sequence. Analysis of the TNFalpha protein coding region indicated 97% homology and of the 3' UTF 89%.

Effects of inhaled nitric oxide and extracorporeal membrane oxygenation on pulmonary hemodynamics and lymph flow in oleic acid lung injury in sheep.

Objective: To compare the effects of inhaled nitric oxide (NO) and extracorporeal membrane oxygenation (ECMO) on oxygenation, hemodynamics, and lymphatic drainage in an oleic acid lung injury model in sheep.

Design: Prospective, randomized study.

Setting: Animal research laboratory.