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Abstract Background A polysulfone dialysis membrane containing both polyvinylpyrrolidone (PVP) and the novel hydrophilic polymer (NV polymer) has been developed in an attempt to modify the blood contact surface of the membrane. In the present study, we performed an in vitro evaluation of the NV polymer-embedded membrane (NV membrane), focusing on the adhesion of blood cells to the membrane and the interferon (IFN)-γ production capacity of peripheral blood mononuclear cells coming in contact with the membrane. Methods Two membranes, the NV membrane and the conventional membrane embedded with PVP alone (CX), were evaluated simultaneously by dividing the porcine blood obtained from the same animal into two portions. The blood cell adhesion to the membranes was evaluated by measuring the hemoglobin concentrations and lactate dehydrogenase (LDH) activities in the eluates extracted from the membranes. The IFN-γ production capacity in response to phytohemagglutinin stimulation of mononuclear cells coming in contact with either membrane was evaluated. Results Both the hemoglobin concentration and LDH activity, corrected by excluding erythrocytes from the eluate, were about 25% lower in the eluate from the NV membrane than in the eluate from the CX membrane. The IFN-γ production capacity of the mononuclear cells coming in contact with dialysis membrane remained unchanged for the case of the NV membrane, while it decreased for the case of the CX membrane. Conclusions A lower degree of adhesion of blood cells to the membrane and a lower degree of reduction in the IFN-γ production capacity of mononuclear cells coming in contact with the membrane were observed for the NV membrane, as compared with the PVP membrane, which may suggest improved biocompatibility of the NV membrane.

Abstract Background When polymethyl methacrylate (PMMA) membranes are used in continuous renal replacement therapy, especially in patients with high cytokine levels, inflammatory cytokines and other substances are removed by the adsorption effect. However, such filters are prone to clogging, and the filter lifetime can be short. This study investigated the effects of hollow fiber inner diameter and membrane area on filter lifetime and protein removal performance using an in vitro continuous hemofiltration (CHF) experimental model with porcine blood. Methods Three types of filters with different hollow fiber inner diameters and membrane areas were used: CH-1.0N (membrane material, PMMA; membrane area, 1.0 m2; hollow fiber inner diameter, 200 µm), CH-1.0W (prototype: PMMA; 1.0 m2; 240 µm), and CH-1.8W (PMMA; 1.8 m2; 240 µm). During the experiment, pressure changes, filter lifetime measured from pressure and protein removal performance were measured using an in vitro CHF experimental model with porcine blood. Results The filter lifetime of CH-1.8W was significantly longer than those of CH-1.0N and CH-1.0W. The total protein adsorption was significantly higher for the CH-1.0W and CH-1.8W filters than for the CH-1.0N filter. Conclusions A larger membrane area from 1.0 to 1.8 m2 contributed to a longer filter lifetime, while an increase in the hollow fiber inner diameter from 200 to 240 µm did not. On the other hand, the protein removal performance, especially the adsorption performance, was higher for membranes with a larger hollow fiber inner diameter from 200 to 240 µm.

Abstract Background and Aims Clotting within the membrane and/or venous ‘air trap’ chamber is common problems during continuous blood purification therapy. Frequent clotting during continuous blood purification therapy leads to inadequate solute removal, an increased circuit and filter cost, and an increased burden for the medical staff. Improvements in filter membrane materials may reduce the extent of clotting and prolong the filter life. The purpose of the present study was to clarify the characteristics of an NV polymer-embedded membrane (NV-PS) after long-term use, especially the adhesiveness of blood cells and changes in the solute removal performance. Methods Continuous hemofiltration (CHF) experiments using a permeate recycle mode were performed for 24 h using the same porcine whole blood divided into two portions to compare the NV-PS with a conventional polysulfone membrane (PS). The activated clotting time was adjusted to within a range of 300–400 s. The change in the dextran sieving coefficient (SC) of the membrane and the residual blood clots in the filters were evaluated after the completion of the CHF experiment. Results The increase in the transmembrane pressure and the pressure drop of the hemofilter were significantly smaller using the NV-PS than with the PS. For larger molecules (SC $$ \leqq $$ ≦ 0.4), the reduction in SC after blood contact was significantly smaller for the NV-PS. Fewer blood cells remained in the residual blood clots when the NV-PS was used. Conclusion NV-PS has the advantages of showing a lower degree of reduction of the solute removal performance and also a lower degree of clogging of the hollow fibers during prolonged circulation. These characteristics may be expected to be advantageous when this membrane is used for continuous blood purification therapy in acute-phase patients.

Abstract Objective To elucidate the genetic background and genotype‐phenotype correlations for epilepsy with myoclonic‐atonic seizures, also known as myoclonic‐astatic epilepsy (MAE) or Doose syndrome. Methods We collected clinical information and blood samples from 29 patients with MAE. We performed whole‐exome sequencing for all except one MAE case in whom custom capture sequencing identified a variant. Results We newly identified four variants: SLC6A1 and HNRNPU missense variants and microdeletions at 2q24.2 involving SCN1A and Xp22.31 involving STS. Febrile seizures preceded epileptic or afebrile seizures in four patients, of which two patients had gene variants. Myoclonic‐atonic seizures occurred at onset in four patients, of which two had variants, and during the course of disease in three patients. Variants were more commonly identified in patients with a developmental delay or intellectual disability (DD/ID), but genetic status was not associated with the severity of DD/ID. Attention‐deficit/hyperactivity disorder and autistic spectrum disorder were less frequently observed in patients with variants than in those with unknown etiology. Significance MAE patients had genetic heterogeneity, and HNRNPU and STS emerged as possible candidate causative genes. Febrile seizures prior to epileptic seizures and myoclonic‐atonic seizure at onset indicate a genetic predisposition to MAE. Comorbid conditions were not related to genetic predisposition to MAE.

Abstract Background Dialysis membranes that release nitric oxide (NO) from their surface, mimicking one of the functions of endothelial cells, may suppress platelet reactivity during hemodialysis treatment. The aim of the present study was to examine whether the addition of a NO donor to the dialysis fluid can suppress platelet reactivity during dialysis. Methods Porcine whole blood was circulated for 4 h through a polysulfone (PS) dialyzer or polymethylmethacrylate (PMMA) dialyzer. After the blood was circulated through the blood circuit and dialyzer, sodium nitroprusside was added to the dialysis fluid as a NO donor. The changes in the platelet reactivity, measured by the platelet aggregation activity by the addition of adenosine diphosphate or collagen in the blood sample, were evaluated during ex vivo dialysis experiments in the presence of a dialysis fluid containing or not containing a NO donor. Results The platelet aggregation activity was significantly decreased at 30 min after the start of the experiment in the case where nitroprusside was added to the dialysis fluid (the NO (+) condition) as compared to the case where no nitroprusside was added to the dialysis fluid (the NO (−) condition), for both the PS and PMMA membranes. The suppression of the platelet reactivity in the NO (+) condition was sustained until the end of the experimental period (240 min). The platelet cyclic guanosine monophosphate level was also significantly increased in the NO (+) condition as compared to the NO (−) condition. Conclusions NO in the dialysis fluid appears to be capable of suppressing the increase of the platelet reactivity observed during dialysis.

Abstract Background In patients undergoing home dialysis, conventionally, Kt/V has been regarded as an index of the removal efficiency per dialysis session. However, more recently, it has been considered that the hemodialysis product (HDP), rather than the Kt/V, is better associated with the clinical symptoms and outcomes in patients undergoing short daily dialysis or nocturnal dialysis. Nevertheless, the HDP lacks a theoretical background, and it does not take into consideration the dialyzer clearance or patient’s body size. The aims of the present study were to clarify the theoretical validity of HDP focusing on its association with solute concentration by computer simulation and to propose a new index of hemodialysis adequacy. Methods We used compartment models and calculated the time course of urea and β2 microglobulin (β2MG) concentrations to determine the peak concentrations and time-averaged concentrations at varying dialysis frequencies (n = 2–7 sessions/week) and durations of dialysis per session (t = 1 to 8 h dialysis sessions). Results It was found that the peak concentrations of urea and β2MG were significantly correlated with the HDP. Based on this, we theoretically extracted the factor related to the peak concentration and defined the squared frequency-Kt/V (sf-Kt/V), as a new index for determining hemodialysis adequacy (sf-Kt/V = n 2 Kt/V; K, clearance; V, solute distribution volume; n, frequency; t, dialysis time); this index was well correlated with the peak concentrations of urea and β2MG, even when the values of K and V were changed. Conclusions Since the sf-Kt/V is an index that reflects peak concentrations of urea and β2MG, which takes into account the dialysis frequency, session duration, dialyzer clearance, and the body weight of the patient, it will be a very useful tool for determining appropriate dialysis schedules and dialysis conditions for individual patients.