The inflammatory response to pathogen-associated molecular patterns such as lipopolysaccharide (LPS) in sepsis is mediated via Toll-like receptors (TLRs). Since TLRs also trigger various immune functions, including phagocytosis, their modulation is a promising strategy in the treatment of sepsis. As antibiotics have immunomodulatory properties, this study examined the effect of commonly used classes of antibiotics on i) the expression of TLRs and cytokines and ii) the phagocytic activity under sepsis-like conditions in vitro. This was achieved by incubating THP-1 monocytes and peripheral blood mononuclear cells (PBMCs) obtained from patients after open-heart surgery with the addition of LPS and six key antibiotics (piperacillin, doxycycline, erythromycin, moxifloxacin or gentamicin). After 24h, mRNA levels of both cytokines (IL-1β, IL-6) and TLRs (1, 2, 4, and 6) were monitored and phagocytosis was determined following coincubation with Escherichia coli. Each antibiotic differentially regulated the gene expression of the investigated TLRs and cytokines in monocytes. Erythromycin, moxifloxacin and doxycyclin displayed the strongest effects and changed mRNA-levels of the investigated genes up to 5.6-fold. Consistent with this, antibiotics and, in particular, moxifloxacin, regulated the TLR-and cytokine expression in activated PBMCs obtained from patients after open-heart surgery. Furthermore, piperacillin, doxycyclin and moxifloxacin inhibited the phagocytic activity of monocytes. Our results suggest that antibiotics regulate the immune response by modulating TLR- and cytokine expression as well as phagocytosis under septic conditions. Moxifloxacin, doxycycline and erythromycin were shown to possess the strongest immunomodulatory effects and these antibiotic classes should be considered for future immunomodulatory studies in sepsis.

The population pharmacokinetic analysis of propofol/alfentanil for ICU sedation therapy revealed increased volumes of drug distribution and decreased elimination characteristics as compared to pharmacokinetic data from short-term infusions in surgical patients. This can be attributed in part to altered distribution/redistribution processes and/or drug elimination under the condition of ICU therapy. No significant drug accumulation was observed. For future long-term sedation and analgesia of ICU patients with propofol/alfentanil, this altered pharmacokinetic behaviour should be taken into consideration to allow a more individualized and safer dosing of this drug combination.

Severe trauma leads to considerable losses of nitrogen in the first days after the accident. As nutritional efforts cannot reduce these losses sufficiently, an adjunctive therapy using the anabolic steroid nandrolone decanoate (Nd) was applied. In a double-blind study 10 male multiple-traumatized patients each received 50 mg of Nd on day 3 and 25 mg of Nd on day 6 after the trauma, an additional 10 patients received placebo only. Both groups had identical nutritional support. Nitrogen balance, total nitrogen excretion as well as plasma amino acid concentration, and urine amino acid excretion were measured daily. The anabolic agent improved the nitrogen balance mainly by reducing nitrogen excretion. 3-Methylhistidine excretion and renal amino acid losses were decreased. Nandrolone decanoate increased the concentration of total plasma amino acids. The underlying principle seems to be an amino acid-saving mechanism with a renal site of action. It is shown that in the early posttraumatic period nandrolone decanoate improves nitrogen metabolism. Further studies are required to determine whether this offers a clinical benefit to trauma patients.

No abstract

For temporary hepatic assistance we used 200 g porcine liver pieces (5 X 5 X 5 mm3) which were perfused for 6 h with 11 swine blood. ATP and energy reserve values reached their maxima 30 min after starting perfusion, remained unchanged for 120 min, and decreased thereafter. Following 30 min of perfusion energy charge values increased from 0.260 +/- 0.110 mumol/g to 0.560 +/- 0.093 mumol/g (normal value; 0.854 +/- 0.022 mumol/g) and thereafter remained unchanged for 6 h. These results suggest that good energy regulation was maintained in the liver pieces. The small liver cubes showed excellent ammonia and phenol detoxication. However, the liver pieces were not found to be able to conjugate serum bilirubin, which might have been caused by a lack of this anatomic pathway in our model. Levels of hepatic and lytic enzymes in the perfusate increased with the time of perfusion, though they were relatively low as compared to levels in patients with acute hepatic failure. The concentration of free fatty acids in the perfusate, which are known to potentiate hepatic coma, increased slightly. However, methyl mercaptane remained constant during perfusion. Concentrations of nearly all amino acids rose during 6-h perfusion due to damage of hepatic tissues, but the molar ratio of the branched chain amino acid to aromatic amino acid was not changed. These results suggest that liberated substances from the damaged liver would not potentiate hepatic encephalopathy. We feel that hemoperfusion over small liver pieces could be a useful method for hepatic assistance.