Introduction The aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours.

Zinc is an essential trace element for both pathogens and hosts. Hypozincemia is a well known phenomenon in sepsis patients and represents the innate immune systems attempt to deprive pathogens of zinc. However little is known about course, restitution and prognostic value of serum zinc levels in sepsis patients. We performed a prospective observational single-center study set in a tertiary care university hospital intensive care unit. Serum zinc levels were singularly measured of healthy controls and sequentially of surgical sepsis patients and surgical patients over a 8-day period. Throughout the study period, we report significantly decreased serum zinc levels in surgical and surgical sepsis patients compared to healthy controls. Lower serum zinc levels in surgical sepsis patients were associated with a higher susceptibility to a recurrent sepsis episode. Furthermore, surgical sepsis patients with a higher number of organ dysfunctions and increased in-hospital mortality at day 28 and 90 showed lower serum zinc levels at admission. We report serum zinc levels as a promising biomarker in the diagnosis and evaluation of sepsis patients. However, it is still unclear whether these findings are caused by an over-amplified redistribution of zinc during acute-phase response, or whether the critically ill patients were zinc deficient before sepsis.

IntroductionIncreasing rates of multi-resistant bacteria are a major problem in the treatment of critically ill patients. Furthermore, conventional antibiotics lead to the release of bacterial derived membrane parts initiating pro-inflammatory cascades with potential harm to the patient. Antimicrobial peptides (AMP) may kill bacteria without releasing pro-inflammatory factors. Thus, we compared three newly developed synthetic anti-lipopolysaccharide peptides (SALPs) with a broader range of efficacy to suppress cytokine release in plasma and CD14 mRNA expression in organ tissue in a murine, polymicrobial sepsis model.MethodsA randomized, experimental trial was conducted in an animal research facility. Male NMRI mice (n = 90; 8- to 12-weeks old) were randomized to the following six groups: (i) sham operation and parenteral vehicle (NaCl 0.9%) administration (sham); (ii) cecal ligation and puncture (CLP) and vehicle infusion (sepsis-control), (iii) CLP and polymyxin B infusion (polyB), or (iv to vi) CLP and infusion of three different synthetic antimicrobial peptides Peptide 19-2.5 (Pep2.5), Peptide 19-4 (Pep4) or Peptide 19-8 (Pep8). All animals underwent arterial and venous catheterization for hemodynamic monitoring 48 hours prior to CLP or sham-operation. Physical appearance and behavior (activity), plasma cytokine levels, and CD14 mRNA expression in heart, lung, liver, spleen and kidney tissue were determined 24 hours after CLP or sham operation.ResultsOnly Pep2.5 significantly enhanced the activity after CLP, whereas none of the therapeutic regimens elevated the mean arterial pressure or heart rate. The strongly elevated IL-6, IL-10 and monocyte chemoattractant protein serum levels in septic animals were significantly reduced after Pep2.5 administration (P < 0.001, P < 0.001, and P < 0.001, respectively). Similarly, Pep2.5 significantly reduced the sepsis-induced CD14 mRNA expression in heart (P = 0.003), lung (P = 0.008), and spleen tissue (P = 0.009) but not in kidney and liver.ConclusionsStructurally variable SALPs exhibit major differences in their anti-inflammatory effect in vivo. Continuous parenteral administration of Pep2.5 is able to reduce sepsis-induced cytokine release and tissue inflammation.