Thrombogenicity and long-term cytokine removal capability of a novel asymmetric triacetate membrane hemofilter.

Hemofilters applied in continuous renal replacement therapies (CRRTs) for the treatment of acute kidney injury must meet high standards in biocompatibility and permeability for middle and large molecules over extended treatment times. In general, cellulose-based membranes exhibit good biocompatibility and low fouling, and thus appear to be beneficial for CRRT. In this in vitro study, we compared a novel asymmetric cellulose triacetate (ATA) membrane with three synthetic membranes [polysulfone (PS), polyethersulfone (PES), and polyethylenimine-treated acrylonitrile/sodium methallyl sulfonate copolymer (AN69 ST)] regarding thrombogenicity and cytokine removal. For thrombogenicity assessment, we analyzed the thrombin-antithrombin complex (TAT) generation in human whole blood during 5 h recirculation and filtration. Sieving coefficients of interleukin-6 (IL-6), IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α) were determined using human plasma as test fluid. ATA and AN69 ST membrane permeability were determined also during long-term experiments (48.5 h). ATA exhibited the lowest TAT generation (6.3 µg/L at 5 h), while AN69 ST induced a pronounced concentration increase (152.1 µg/L) and filter clogging during 4 out of 5 experiments. ATA (IL-8: 1.053; IL-6: 1.079; IL-10: 0.898; TNF-α: 0.493) and PES (0.973; 0.846; 0.468; 0.303) had the highest sieving coefficients, while PS (0.697; 0.100; 0.014; 0.012) and AN69 ST (N/A; 0.717; 0; 0.063) exhibited lower permeability. Long-term experiments revealed stronger fouling of the AN69 ST compared to the ATA membrane. We observed the highest permeability for the tested cytokines, the lowest thrombogenicity, and the lowest fouling with the ATA membrane. In CRRT, these factors may lead to increased therapy efficacy and lower incidence of coagulation-associated events.

Acetylene dithiolate linking up the [Tp'W(CO)(CN)] moiety with Ru(II) or Pd(II.).

A series of heterodinuclear complexes with acetylene dithiolate (acdt(2-) ) as the bridging moiety were synthesised by a facile one-pot procedure that avoided use of the highly elusive acetylene dithiol. Generation of the W-Ru complex [Tp'W(CN)(CO)(C2 S2 )Ru(η(5) -C5 H5 )(PPh3 )] (Tp'=hydrotris(3,5-dimethylpyrazolyl)borate) and the W-Pd complexes [Tp'W(CN)(CO)(C2 S2 )Pd(dppe)] and [Tp'W(CO)2 (C2 S2 )Pd(dppe)][PF6 ] (dppe=1,2-bis(diphenylphoshino)ethane), which exhibit a [W(η(2) -κ(2) -C2 S2 )M] core (M=Ru, Pd), was accomplished by using a transition-metal-assisted solvolytical removal of the Me3 Si-ethyl thiol protecting groups. All intermediate species of the reaction have been fully characterised. The highly coloured W-Ru complex [Tp'W(CN)(CO)(C2 S2 )Ru(η(5) -C5 H5 )(PPh3 )] shows reversible redox chemistry, as does the prototype complex [Tp'W(CO)2 (C2 S2 )Ru(η(5) -C5 H5 )(PPh3 )][PF6 ]. Single crystal X-ray diffraction and IR, EPR and UV/Vis spectroscopic studies in conjunction with DFT calculations prove the high electronic delocalisation of states over the acdt(2-) linker. Comparative studies revealed a higher donor strength and more pronounced dithiolate character of acdt(2-) in [Tp'W(CN)(CO)(C2 S2 )Ru(η(5) -C5 H5 )(PPh3 )] relative to [Tp'W(CO)2 (C2 S2 )Ru(η(5) -C5 H5 )(PPh3 )](+) . In addition, the influence of the overall complex charge on the metric parameters was investigated by single-crystal X-ray diffraction studies with the W-Pd complexes [Tp'WL2 (C2 S2 )Pd(dppe)] (L=(CN(-) )(CO) or (CO)2 ). The central [W(C2 S2 )Pd] units exhibit high structural similarity, which indicates the extensive delocalisation of charge over both metals.