Evaluation of Proteins and Cells that Adsorb to Dialysis Membranes Used in Continuous Hemodiafiltration: Comparison of AN69ST, Polymethylmethacrylate, and Polysulfone Membranes.

OBJECTIVE: In intensive care medicine, continuous renal replacement therapy (CRRT) is important for critically ill patients. Various types of dialysis membranes are currently used in clinical settings, each having unique structures and characteristics. This study aimed to perform a detailed analysis of the characteristics of polysulfone (PS), polymethylmethacrylate (PMMA), and polyacrylonitrile (AN69ST) membranes, and to determine differences in the adsorption of proteins and blood cells by membrane material. METHODS: Subjects were patients undergoing CRRT in the ICU of the Kokura Memorial Hospital. After use, membranes were collected and analyzed. Semi-quantitative analysis of the membrane surface was performed by scanning electron microscopy. We determined the identity of proteins adsorbed to the surface of membranes by TOF/MS analysis, and measured the amount of adsorbed chemical mediators. RESULTS: Electron microscopy revealed that, compared to PS and PMMA membranes, AN69ST membranes had a greater amount of adsorbed activated white blood cells (WBCs). A large amount of platelets was adsorbed to PMMA membranes. In terms of the amount of adsorbed protein, significantly more proteins adsorbed to AN69ST membranes compared to PS and PMMA membranes. Moreover, TOF/MS analysis revealed a difference in the types of adsorbed proteins by membrane. Chemokines were particularly prevalent among adsorbed proteins for all 3 membranes. CONCLUSION: Compared to PS and PMMA membranes, AN69ST membranes had a higher capacity to remove activated WBCs. Moreover, apparent differences were noted in the types of proteins that adsorbed to each type of membrane. These differences in membrane properties may impact clinical outcomes.

alpha-Tocopheryl-L-ascorbate-2-O-phosphate diester, a hydroxyl radical scavenger, prevents the occurrence of epileptic foci in a rat model of post-traumatic epilepsy.

Intracortical injection of iron ions has been used to model post-traumatic epilepsy. The results obtained using these models suggest that oxidation of neural membranes by active oxygen free radicals may be involved in the etiology of post-traumatic epilepsy. This is a study of the effects of alpha-tocopheryl-L-ascorbate-2-O-phosphate diester potassium salt (EPC-K1), known as a hydroxyl radical scavenger, on the peroxidation of neural membranes by FeCl(3) in vitro and on the occurrence of epileptic discharges in the FeCl(3) injected post-traumatic epilepsy model rats. EPC-K1 dose-dependently inhibited the production of thiobarbituric acid reactive substances (TBARS) and protein carbonyl (P-Carb), both indices of biogenic macromolecular peroxidation. In vivo studies, sporadic spike discharges and/or epileptiform activities were observed in electrocorticograms (ECoG) of male Sprague-Dawley rat 15-90 min after 500 nmol of FeCl(3) was injected into the motor cortex. On the other hand, when 200 mg/kg of EPC-K1 was injected intraperitoneally 60 min prior to the injection of FeCl(3), the occurrence of epileptic discharges was prevented or delayed. When EPC-K1 (2.5-5 nmol) was injected along with the ferric ions, the occurrence of epileptiform activities was also prevented or delayed. EPC-K1 prevented the induction of early convulsion, the major risk factor of post-traumatic epilepsy. Rats in the Fe+EPC group were injected with 500 nmol of FeCl(3) into the left motor cortex and were given an EPC-K1-diet (CE-2 chow contained 0.2% of EPC-K1, and daily EPC-K1 intake was about 80 mg/kg/day). In the Fe+EPC group rats, the percent induction of epileptic discharges in ECoGs was significantly lower than that in the Fe+CE group rats, which were fed CE-2 after FeCl(3) injection. In the homotropic contra lateral cortex, TBARS and P-Carb content did not show any changes. However, the relative TBARS content in the focal area significantly increased in the Fe+CE and Fe+EPC group rats 3 h after the injection. It became normal 3 days after in the Fe+EPC group. The relative P-Carb content in the focal area significantly increased in the Fe+CE and Fe+EPC group rats 3 h after the injection. However, it became normal after 3 days. In the present study, EPC-K1, which consists of vitamins E and C connected by a phosphate, protected the oxidation of neural membranes and prevented the occurrence of ferric ion-induced epileptic discharges by its radical scavenger activity. These data suggest that EPC-K1 may be clinically useful in not only preventing the focus formation of post-traumatic epilepsy, but also in treating and attenuating the progression of free radical-induced degenerative disorders.