Compatibility of common drugs with acetate-containing balanced electrolyte solutions in pediatric anesthesia.

BACKGROUND: Acetate-containing balanced electrolyte solutions are frequently used for fluid therapy in pediatric anesthesia, but no studies investigating the compatibility with common anesthetic drugs are available. AIM: To reveal possible incompatibilities between common anesthetic drugs and the acetate-containing balanced electrolyte solutions BS (Sterofundin ISO; B.Braun Melsungen AG, Melsungen, Germany) and BS-G1 (E148G1 Päd; Serumwerk Bernburg AG, Bernburg, Germany), with normal saline (NS) as control. METHODS: All tested infusion solutions were mixed 1 : 1 with 28 common anesthetic drugs in concentrations used in daily clinical practice. Electrical conductivity, pH, and turbidimetric light diffusion at 405 nm were measured. Macroscopic changes such as gross precipitation, change in color, or bubble formation were also assessed. All measurements were performed immediately after mixing as well as 30 and 60 min after. RESULTS: The vast majority of drugs showed no significant change in pH, electric conductivity, turbidimetric detectable light diffusion, or macroscopic appearance after mixing with BS, BS-G1, and NS. Phenytoin immediately precipitated in response to all tested solutions as did diazepam. Thiopental precipitated after mixing with BS only. CONCLUSIONS: Most of the tested drugs did not show any signs or evidence of incompatibility reactions. However, phenytoin and diazepam should not be in contact with the three tested solutions, including NS. Thiopental should be used with caution because it can precipitate in solutions with a low pH (e.g., BS).

Critical role for syndecan-4 in dendritic cell migration during development of allergic airway inflammation.

Syndecan-4 (SDC4), expressed on dendritic cells (DCs) and activated T cells, plays a crucial role in DC motility and has been shown as a potential target for activated T-cell-driven diseases. In the present study, we investigate the role of SDC4 in the development of T-helper 2 cell-mediated allergic asthma. Using SDC4-deficient mice or an anti-SDC4 antibody we show that the absence or blocking of SDC4 signalling in ovalbumin-sensitized mice results in a reduced asthma phenotype compared with control animals. Most importantly, even established asthma is significantly decreased using the anti-SDC4 antibody. The disturbed SDC4 signalling leads to an impaired motility and directional migration of antigen-presenting DCs and therefore, to a modified sensitization leading to diminished airway inflammation. Our results demonstrate that SDC4 plays an important role in asthma induction and indicate SDC4 as possible target for therapeutic intervention in this disease.

Plasmin- and thrombin-accelerated shedding of syndecan-4 ectodomain generates cleavage sites at Lys(114)-Arg(115) and Lys(129)-Val(130) bonds.

Syndecans are transmembranous heparan sulfate proteoglycans abundant in the surface of all adherent mammalian cells and involved in vital cellular functions. In this study, we found syndecan-1, -2, -3, and -4 to be constitutively expressed by human umbilical vein endothelial cells. The exposure of the ectodomains of syndecan-1 and -4 to the cell surface and their constitutive shedding into the extracellular compartment was measured by immunoassays. In the presence of plasmin and thrombin, shedding was accelerated and monitored by detection and identification of (35)S-labeled proteoglycans. To elucidate the cleavage site of the syndecan ectodomains, we used a cell-free in vitro system with enzyme and substrate as the only reactants. For this purpose, we constructed recombinant fusion proteins of the syndecan-1 and -4 ectodomain together with maltose-binding protein and enhanced yellow fluorescent protein as reporter proteins attached to the N and C termini via oligopeptide linkers. After protease treatment of the fusion proteins, the electrophoretically resolved split products were sequenced and cleavage sites of the ectodomain were identified. Plasmin generated cleavage sites at Lys(114) downward arrowArg(115) and Lys(129) downward arrowVal(130) in the ectodomain of syndecan-4. In thrombin proteolysates of the syndecan-4 ectodomain, the cleavage site Lys(114) downward arrowArg(115) was also identified. The cleavage sites for plasmin and thrombin within the syndecan-4 ectodomain were not present in the syndecan-1 ectodomain. Cleavage of the syndecan-1 fusion protein by thrombin occurred only at a control cleavage site (Arg downward arrowGly) introduced into the linker region connecting the ectodomain with the enhanced yellow fluorescent protein. Because both plasmin and thrombin are involved in thrombogenic and thrombolytic processes in the course of the pathogenesis of arteriosclerosis, the detachment of heparan sulfate-bearing ectodomains could be relevant for the development of arteriosclerotic plaques and recruitment of mononuclear blood cells to the plaque.