Application and Efficacy of Vitamin E-Bonded Polysulfone Membrane in Acute Blood Purification Therapy.

INTRODUCTION: Acute blood purification therapy (BPT) has been evaluated in the context of intensive care for serious conditions related to systemic inflammation, but its mechanism and efficacy are not fully understood. OBJECTIVE: This study examined the feasibility of using vitamin E-bonded polysulfone membranes (VEPS) for BPT in a LPS-induced rat model of systemic inflammation. METHODS: To evaluate the efficacy of BPT with a VEPS membrane, polysulfone (PS) membranes conventionally used in intensive care were bonded with the antioxidant vitamin E and used in a rat model of lipopolysaccharide (LPS)-induced systemic inflammation. BPT using a PS membrane (PS group) or a VEPS membrane (VEPS group) was performed 6 h after administration of LPS. Extracorporeal circulation was established in normal rats as a control (sham group). Survival rates, histology of lung specimens, and levels of myeloperoxidase (MPO) and high mobility group box-1 (HMGB-1) were examined in each group. RESULTS: Survival rates at 24 h after LPS administration were 100% in the VEPS group and 50% in the PS group. Pulmonary architecture was largely maintained and the level of infiltration of inflammatory cells remained moderate in the VEPS group. Levels of active MPO before and after BPT were significantly higher in the PS and VEPS groups than in the sham group, with no significant differences between the PS and VEPS groups. HMGB-1 levels were significantly elevated after BPT in the PS group. CONCLUSIONS: This study demonstrated that use of the VEPS membrane for BPT increased survival rate and reduced lung injury in a rat model of systemic inflammatory response syndrome (SIRS), suggesting the possible use of VEPS membranes in the treatment of serious conditions related to systemic inflammation.

In vitro blood compatibility evaluation method: incubating while rotating hemodialyzers filled with fresh human blood.

One of the often-used methods for in vitro evaluation of the blood compatibility of hemodialysis membranes is the circulation of human blood through a miniaturized hemodialyzer. The use of a rather small amount of human blood in its evaluation is one advantage of this method. However, because it is manufactured by a different process than actual ones, a miniaturized hemodialyzer membrane cannot always preserve the properties of actual hemodialyzers. To address this problem, we established a new experimental method that uses a relatively small amount of human blood and actual dialyzers. In this method, a test hemodialyzer and a control hemodialyzer filled with human blood obtained from the same donor is slowly rotated to prevent spontaneous blood cell sedimentation for 4 h at 37 °C. By use of this method, we were able to compare blood compatibility between a polysulfone (PS) membrane and a vitamin E (VE)-bonded PS membrane in terms of their relative antithrombotic, antioxidative, and anti-inflammatory properties. Consistent with many previous reports, the results clearly showed that compared with the PS membrane, VE-bonded PS membrane is more blood compatible. These findings suggest that our method is applicable, at least to in vitro blood compatibility evaluation of PS type dialysis membranes.

Vitamin E-Coated Polysulfone Membrane-Based Hemodiafiltration Attenuates Inflammation in a Rat Model of Lipopolysaccharide-Induced Systemic Inflammation.

BACKGROUND: Acute blood purification (ABP) therapy is used regularly in the clinical setting and reportedly alleviates organ failure associated with severe systemic inflammatory responses, leading to reduced mortality. The present study aimed to determine whether there is a difference in efficacy between polysulfone (PS) membranes, which are currently used regularly in the clinical setting, and vitamin E-coated polysulfone (VEPS) membranes, which are anticipated to exhibit the antioxidant and anti-inflammatory properties of vitamin E. METHODS: Male Wistar rats (n=15/group) were intravenously administered 10 mg/kg of lipopolysaccharide (LPS) to establish a systemic inflammatory response model. Six hours after LPS administration, hemodiafiltration (HDF) was performed for 30 minutes using a PS or VEPS membrane under general anesthesia. Blood was collected at various time points, lung tissue was evaluated histologically, and 24-hour survival was assessed. RESULTS: The rats in the VEPS group tended to have a higher survival rate than those in the PS group when undergoing HDF, although the difference was not significant. With respect to lung tissue, the inflammatory response was suppressed to a greater extent in the VEPS group than the PS group. Serum interleukin (IL)-6 levels were reduced at an early stage, plasma antioxidant activity was increased, and oxidative stress was reduced in the VEPS group compared to the PS group. CONCLUSION: Relative to PS membrane-based HDF, the survival rate tended to improve and inflammation was subdued earlier due to the antioxidant activity and early attenuation of inflammation associated with VEPS membrane-based HDF.

Adsorption properties of an activated carbon for 18 cytokines and HMGB1 from inflammatory model plasma.

The ability of an activated carbon (AC) to adsorb 18 different cytokines with molecular weights ranging from 8 kDa to 70 kDa and high mobility group box-1 (HMGB1) from inflammatory model plasma at 310 K and the mechanisms of adsorption were examined. Porosity analysis using N2 gas adsorption at 77K showed that the AC had micropores with diameters of 1-2 nm and mesopores with diameters of 5-20 nm. All 18 cytokines and HMGB1 were adsorbed on the AC; however, the shapes of the adsorption isotherms changed depending on the molecular weight. The adsorption isotherms for molecules of 8-10 kDa, 10-20 kDa, 20-30 kDa, and higher molecular weights were classified as H-2, L-3, S-3, and S-1 types, respectively. These results suggested that the adsorption mechanism for the cytokines and HMGB1 in the mesopores and on the surface of the AC differed as a function of the molecular weight. On the basis of these results, it can be concluded that AC should be efficient for cytokine adsorption.

Screening and analysis of adsorbents for pemphigus autoantibodies.

Pemphigus represents a potentially life-threatening, blistering, chronic autoimmune disease involved with autoantibodies against desmosomal adhesion proteins, desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3). These autoantibodies belong to biased immunoglobulin subclasses, predominantly IgG1 and IgG4. Although plasmapheresis is established for the treatment of pemphigus, specific immunoadsorption of the autoantibodies has not been clinically applied. In order to search for a novel adsorbent for the pemphigus autoantibodies, we screened a library of 26 chemical ligand adsorbents using the effluent of double filtration plasmapheresis obtained from pemphigus patients. As a result of the screening, we found that each adsorbent whose ligand is 2-thiophene ethylamine, tryptophan, para-guanidinophenylalanine, phenylalanine, or thienylglycine adsorb both antibodies to Dsg3 and Dsg1 efficiently, in that order. Furthermore, the thiophene adsorbent exhibited a high affinity for the IgG4 subclass. These results suggest that the thiophene adsorbent may be suitable for pemphigus immunoadsorption. Further in vivo animal studies and clinical trials are needed.