Efficacy of naftopidil for nocturia in male patients with lower urinary tract symptoms: comparison of morning and evening dosing.

OBJECTIVES: To examine the difference in improvement of lower urinary tract symptoms between morning and evening dosing of α1 -blocker naftopidil. METHODS: A total of 177 male patients with nocturia were included in the present study and randomized to morning or evening dosing of naftopidil. The International Prostate Symptom Score, quality of life index and nocturia quality of life index were compared between the two study groups at 12 weeks. RESULTS: A total of 143 patients (morning group: n = 70, evening group: n = 73) were analyzed as a result of the dropout of 34 patients because of failure to give consent, adverse events and failure to attend. Nocturia, quality of life index and nocturia quality of life index at 12 weeks were significantly better in the evening group compared with the morning group. In a multivariate model, both the dosing time of naftopidil and the initial nocturia quality of life index were significantly associated with change in nocturia quality of life index. CONCLUSIONS: Evening dosing of naftopidil seems to be more effective in treating nocturia in male patients with lower urinary tract symptoms.

Overexpression of orotate phosphoribosyl transferase in hormone-refractory prostate cancer.

Orotate phosphoribosyl transferase (OPRT) is the initial enzyme of 5-fluorouracil (5-FU) activation, in which 5-FU is converted to 5-fluorouridinemonophosphate. Dihydropyrimidine dehydrogenase (DPD) is a degrading enzyme that catabolizes 5-FU. In this study, we investigated the expression of these enzymes in normal prostate gland (NP), hormone-sensitive prostate cancer (HSPC) and hormone-refractory prostate cancer (HRPC). Forty-two prostatic tissue specimens were obtained from patients who had undergone prostate needle biopsies without any treatments or with PSA failure after initial androgen deprivation. The tissue samples derived from formalin-fixed, paraffin-embedded sections were made by laser-captured microdissection and from those RNA was extracted. The levels of OPRT and DPD mRNA expression were examined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The level of OPRT mRNA expression in the HSPC or the HRPC specimens was significantly higher than that in the NP specimens. Immunohistochemical staining for OPRT revealed strong expression of OPRT in prostate cancer cells. There was a significant correlation between OPRT mRNA expression levels and the tumor pathological grade. Furthermore, the OPRT/DPD expression ratio, a powerful predictive factor to evaluate 5-FU sensitivity, in the HRPC group was significantly higher than that in the low grade HSPC group. Thus, 5-FU may be an effective option for some HRPC patients.

Indirect antitumor effects of bisphosphonates on prostatic LNCaP cells co-cultured with bone cells.

Bisphosphonates are strong inhibitors of osteoclastic bone resorption in both benign and malignant bone diseases. The nitrogen-containing bisphosphonates (N-BPs) have strong cytotoxicity via inhibition of protein prenylation in the mevalonate pathway, and also demonstrate direct cytostatic and proapoptotic effects on prostate cancer cells. We confirmed the usefulness of a co-culture system comprised of prostatic LNCaP cells, ST2 cells (mouse-derived osteoblasts) and MLC-6 cells (mouse-derived osteoclasts) in vitro. N-BPs (pamidronate and zoledronic acid) inhibited both androgen receptor transactivation and tumor cell proliferation by suppressing the activities of both osteoclasts and osteoblasts with low-dose exposure. This indirect inhibition of prostate cancer cells via bone cells could be beneficial in treating prostate cancer patients with bone metastases.

Quantitative evaluation of age-related changes to pelvic floor muscles in magnetic resonance images from 369 patients.

AIM: This study aimed to establish and validate a quantitative evaluation method for pelvic floor muscles using magnetic resonance images (MRI) and to examine the morphological change of pelvic floor muscles with aging. METHODS: Data from 369 consecutive patients (163 men, 206 women; median age 58 years; range 17-92 years) who underwent coronal T2-weighted pelvic MRI at Osaka General Hospital between January 2016 and December 2016 were retrospectively examined. MRI of the levator ani muscle was evaluated. The MRI image blinded the patient information and was evaluated by a radiology specialist with 22 years of experience. In coronal T2-weighted MRI of the pelvis, the levator ani muscle was evaluated using the slice; it showed the most upward and downward convexity. We measured the thickness of the levator ani muscle, and the distance at the most convex part from a straight line connecting the origin and insertion of the levator ani muscle on both the left and right sides. Upward and downward convexity was recorded in positive and negative values, respectively. RESULTS: The levator ani muscle was able to be evaluated quantitatively in all cases. Both men and women showed thinning (men: mean 3.316 mm, r = -0.388, P < 0.0001; women: mean 3.947 mm, r = -0.359, P < 0.0001) and concavity (men: mean 1.412 mm, r = -0.362, P < 0.0001; women: mean 4.979 mm, r = -0.630, P < 0.0001) of the levator ani muscle with aging. CONCLUSIONS: A quantitative evaluation method for pelvic floor muscles using MRI was established. Aging was associated with morphological changes in the pelvic floor muscles in both men and women. Geriatr Gerontol Int 2019; 19: 834-837.

Telmisartan is a potent target for prevention and treatment in human prostate cancer.

Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agent. Recent studies have reported that ARBs have the potential to inhibit the growth of prostate cancer (PC) cells. Moreover, it was recently reported that Telmisartan (a kind of ARB) has peroxisome proliferator-activated receptor (PPAR)-gamma activation. We previously reported that PPAR-gamma ligand induces growth arrest of PC cells through apoptosis. In this study, we evaluated the effects of the Telmisartan and other ARBs on cell proliferation in several PC cell lines. We used normal prostate stromal cell (NPC), human hormone-refractory PC (PC3), androgen-independent PC (DU-145) and androgen-dependent PC (LNCaP) cell lines. Effects of Telmisartan and other ARBs (Candesartan, Valsartan, Irbesartan and Losartan) on PC cell growth were examined by MTT assay. Flow cytometry and Hoechst staining were used to determine whether or not ARBs induce apoptosis. Telmisartan caused marked inhibition of PC cells in concentration-dependent and time-dependent manner. PC cells with treatment of 100 microM Telmisartan induced early apoptosis and DNA fragmentation. However, NPC with treatment of 100 microM Telmisartan did not induce apoptosis or DNA fragmentation. Furthermore, other ARBs had no effect on cell proliferation in the PC cells and NPC. Telmisartan may mediate potent antiproliferative effects against PC cells through PPAR-gamma. Thus, Telmisartan is a potent target for prevention and treatment in PC.

Increased levels of serum matrix metalloproteinase-3 in haemodialysis patients with dialysis-related amyloidosis.

BACKGROUND: It is recognized that matrix metalloproteinase-3 (MMP-3) is abundantly expressed in active rheumatoid synovium, and that serum level of MMP-3 is a useful marker for diagnosis of rheumatoid arthritis and for evaluation of prognosis in joint destruction. Little is known about serum MMP-3 levels in haemodialysis (HD) patients, and thus, the association between serum MMP-3 and dialysis-related amyloidosis (DRA) has yet to be elucidated. METHODS: Serum levels of MMP-3 were measured by enzyme immunoassay in 150 HD patients, 90 without DRA and 60 with DRA, before HD. Simple regression analysis was performed to investigate the relationship between serum level of MMP-3 and clinical parameters, including age, HD duration, C-reactive protein and beta2 microglobulin (BMG). RESULTS: Serum levels of MMP-3 were significantly higher in HD patients with DRA than in HD patients without DRA (258.2 +/- 118.1 vs 201.5 +/- 98.4 pg/mL, P = 0.0017), and both levels were significantly higher than those of healthy subjects (45.6 +/- 13.4 pg/mL, P < 0.0001). Serum MMP-3 levels significantly correlated with serum levels of BMG (r = 0.197, P = 0.0164) and HD duration (r = 0.168, P = 0.0427). Moreover, serum MMP-3 levels significantly correlated with serum BMG levels in HD patients without DRA (r = 0.341, P = 0.0012), but not in HD patients with DRA. CONCLUSION: Our results suggest that matrix metalloproteinase activity increases in HD patients, which may be associated with BMG and DRA.

Feedback Control of the Arachidonate Cascade in Osteoblastic Cells by 15-deoxy-Delta-Prostaglandin J(2).

15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-gamma ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ(2) can suppress interleukin (IL)-1beta-induced prostaglandin E(2) (PGE(2)) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE(2) synthesis in osteoblasts by regulation of cyclooxygenase (COX)-2 and regulates osteoclastic bone resorption in various diseases such as RA and osteoporosis. In this study, we investigated the feedback mechanism of the arachidonate cascade in mouse osteoblastic cells, MC3T3-E1 cells, which differentiate into mature osteoblasts. Treatment with 15d-PGJ(2) led to a significant increase in IL-1alpha-induced COX-2 expression and PGE(2) production in a dose dependent manner. The effect of 15d-PGJ(2) was stronger than that of TRO. However, it did not affect the expression of COX-1. In addition, cell viability of MC3T3-E1 cells was not changed in the condition we established. This means that 15d-PGJ(2) exerts a positive feedback regulation of the arachidonate cascade of PGE(2) in osteoblastic cells. These results may provide important information about the pathogenesis and treatment of bone resorption in a variety of diseases such as RA and osteoporosis.

Eicosapentaenoic Acid suppresses the proliferation of synoviocytes from rheumatoid arthritis.

Eicosapentaenoic acid (EPA) is essential for normal cell growth, and may play an important role in inflammatory and autoimmune disorders including rheumatoid arthritis. We investigate that EPA could suppress the proliferation of fibroblast like synoviocytes in vitro. We treated synoviocytes with 1 to 50 microM EPA and measured cell viabilities by the modified MTT assay. We sorted the number of them in sub G1 stage by fluorescence-activated cell sorting caliber. And we stained them by light green or Hoechst 33258, and investigate microscopic appearance. The cell viabilities were decreased at 30 microM, 40 microM, and 50 microM of EPA comparing to 0 microM of EPA. The half maximal concentration of synoviocytes inhibition was approximately 25 microM. At day 1 and day 3, cell number was also decreased at 50 microM EPA comparing to control. FACS caliber indicated the number of synoviocytes in sub G1 stage did not increase in each concentration of EPA. Hoechst staining indicated normal chromatin pattern and no change in a nuclear morphology both in EPA treated synoviocytes and in untreated synoviocytes. These findings suggest that EPA could suppress the proliferation of synoviocytes in vivo dose dependently and time dependently, however, the mechanism is not due to apoptosis.

Overexpression of cysteinyl LT1 receptor in prostate cancer and CysLT1R antagonist inhibits prostate cancer cell growth through apoptosis.

The metabolism of arachidonic acid by either cyclooxygenase or lipoxygenase is believed to play an important role in carcinogenesis. Leukotriene (LT) D4 is a proinflammmatory mediator derived from arachidonic acid through various enzymatic steps, and 5-lipoxygenase is an important factor in generating LTD4. We investigated LTD4 receptor (cysteinyl LT1 receptor: CysLT1R) expression in prostate cancer (PC), as well as the effects of CysLT1R antagonist on cell proliferation in PC cell lines. CysLT1R expression in PC patients, prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), and normal prostate (NP) tissues were examined. CysLT1R expression was detected by immunohistochemistry. Effects of CysLT1R antagonist on PC cell growth were examined by MTT assay. Flow cytometry and Hoechst staining were used to determine whether or not the CysLT1R antagonist induces apoptosis. Initially, only slight CysLT1R expression was detected in BPH and NP tissues and marked CysLT1R expression was detected in PIN and PC tissues. CysLT1R expression was higher in high-grade cancer than in low-grade cancer. Furthermore, CysLT1R antagonist caused marked inhibition of PC cells in a concentration- and time-dependent manner through early apoptosis. In conclusion, CysLT1R is induced in PC, and the results suggest that CysLT1R antagonist may mediate potent anti-proliferative effects of PC cells. Thus, the target of CysLT1R may become a new therapy in the treatment of PC.

Blood purification for critical illness: cytokines adsorption therapy.

Blood purification therapies have been clinically applied to treat cytokine-induced pathological effects. The effects of broad-spectrum adsorption using Lixelle (beta2-microglobulin adsorption column; Kaneka Corporation, Osaka, Japan) for the condition of hypercytokinemia in vitro, in an animal model and in humans with sepsis were investigated. We found that Lixelle could selectively adsorb not only beta2-microglobulin but also cytokines composed of glycoproteins in vitro. In addition, Lixelle beads could adsorb not only endotoxin (ET) but also microbial fragments such as peptidoglycan (PG) which is a component of Gram-positive bacteria. Hypercytokinemic rats were connected to a direct hemoperfusion (DHP) system using a mini Lixelle column and time-course changes in plasma levels of inflammatory cytokines were examined. In addition, a Lixelle column was used in direct hemoperfusion in patients with systemic inflammatory response syndrome (SIRS), and the relationship between a decrease in cytokines and clinical course was examined. The increases in plasma levels of IL-6 and tumor necrosis factor-alpha (TNF-alpha) were significantly inhibited in the group treated with the Lixelle column in an animal model. In humans with sepsis, for IL-1beta, IL-1Ra, IL-6, IL-8, and TNF-alpha, the adsorbing rates in vivo before and after the use of the Lixelle column tended to decrease with time. However, the reduction rates at 5 min after the start were 31.4, 39.3, 36.4, 76.2 and 71.6%, respectively, and at 3 h after the start, the rates were 18.0, 17.7, 12.9, 31.8, and 32.9%, respectively. Clinically, their blood pressure increased and they recovered from shock status. These results suggest that SIRS and sepsis with hypercytokinemia can be treated with the DHP using the Lixelle column.

5-Lipoxygenase inhibitors attenuate growth of human renal cell carcinoma and induce apoptosis through arachidonic acid pathway.

The metabolism of arachidonic acid by either the cyclooxygenase or lipoxygenase (LOX) pathway is believed to play an important role in tumor promotion. We investigated the expression of 5- and 12-LOX in renal cell carcinoma (RCC), as well as the effects of their inhibitors on cell proliferation in 2 RCC cell lines (Caki-1 and A498). Expression of 5- and 12-LOX was detected by immunohistochemistry and RT-PCR. Effects of LOX inhibitors on RCC cell growth were examined by MTT assay, and Hoechst staining was used to determine whether or not the LOX inhibitors induce apoptosis. While 5- and 12-LOX expression levels were slightly detected in NK tissues, marked expressions of 5- and 12-LOX were detected in RCC tissues. 5-LOX inhibitors caused marked reduction of RCC cells in a concentration- and time-dependent manner. The effect of the 5-LOX inhibitor was stronger than the 12-LOX inhibitor. Furthermore, the 5-LOX inhibitor caused a marked reduction of RCC cells through apoptosis. LOX, especially 5-LOX, is induced in RCC, and the results suggest that the 5-LOX inhibitor may mediate potent anti-proliferative effects against RCC cells. Thus, 5-LOX may become a new target in treatment of RCC.

[Relationship between peroxisome proliferator activator-receptor (PPAR) and urological cancer].

Recent studies have demonstrated that peroxisome proliferator activator-receptor (PPAR)-gamma ligand induces growth arrest of cancer cells through apoptosis. In this review, we demonstrated the expression of PPAR-gamma in urological cancer (renal cell carcinoma, bladder tumor, prostate cancer, and testicular tumor) tissues as well as the effects of PPAR-gamma ligands. While no marked expression of PPAR-gamma was observed in normal tissue, significant expression was found in all urological cancer tissue. PPAR-gamma ligands (troglitazone and 15dPGJ2) induced the reduction of cell viability with the half-maximal concentration of growth inhibition of renal cell carcinoma, bladder tumor, and prostate cancer cell lines. Cells treated with PPAR-gamma inhibitors showed typical redundant characteristics of apoptosis. PPAR-gamma ligands may mediate potent antiproliferative effects through differentiation.

[Relationship between cyclooxygenase (COX)-2 and malignant tumors].

Recently, epidemiologic studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs(NSAIDs) reduce the incidence of colorectal carcinoma. Cyclooxygenase(COX) is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandins(PGs) production from arachidonic acid(AA). PGs and COX enzyme may be involved in the initiation and/or the promotion of carcinogenesis because the major action of NSAIDs is the inhibition of COX. In this review, we demonstrated the expression of COX-2 in urological cancer(renal cell carcinoma, bladder tumor, prostate cancer, and testicular tumor) tissues as well as the effects of COX inhibitors.

Tissue factor antisense oligonucleotides prevent renal ischemia-reperfusion injury.

BACKGROUND: Tissue factor (TF) expression is induced on macrophages and endothelial cells during the immune response. We designed an antisense (AS) phosphorothioate oligodeoxynucleotide (ODN) to specifically inhibit the expression of rat TF to study the effects of the AS ODN on renal ischemia-reperfusion injury in the rat. METHOD: AS-1 ODN for TF was delivered intravenously to inhibit the expression of TF in endothelial cells. After 8 hr, the right kidney was harvested and the left renal artery and vein were clamped. The kidney was reperfused after 90 min of ischemia, and rats were killed at 0, 1.5, 5, 12, and 24 hr after reperfusion. TF expression was analyzed by immunohistochemical staining using monoclonal antibody. RESULTS: In the untreated ischemic group, 0 of 20 rats survived beyond day 3. However, treatment with AS-1/TF led to 12 of 20 rats surviving beyond day 4. TF was detected on distal tubular epithelial cells, endothelial cells, and blood vessels but not on necrotic and proximal tubular epithelial cells. The necrotic area extended and encompassed nearly all of the ischemic kidney within 12 hr after reperfusion. The necrotic area and the grade of TF staining were more significantly reduced in the AS-1/TF-treated group than in the control group. Furthermore, fluorescein isothiocyanate-labeled AS-1/TF was significantly intense in tubular epithelial cells 8 hr after intravenous administration. CONCLUSIONS: The results indicate that AS-1/TF inhibited the ischemia-reperfusion injury of the kidney. Microcirculatory incompetence resulting from microthrombus may cause the formation and development of necrosis.

Expression of lipoxygenase in human prostate cancer and growth reduction by its inhibitors.

The metabolism of arachidonic acid by either the cyclooxygenase (COX) or lipoxygenase (LOX) pathway generates eicosanoids, which have been implicated in the pathogenesis of a variety of human diseases, including cancer. They are believed to play important roles in tumor promotion, progression, and metastasis. Involvement of LOXs expression and function in tumor growth and metastasis has been reported in human tumor cell lines. Expressions of 5- and 12-LOX in prostate cancer (PC) patients, prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), and normal prostate (NP) tissues were examined, as well as effects of their inhibitors on cell proliferation in 2 PC cell lines (PC3, DU-145). Expression of 5- and 12-LOX protein was detected by immunohistochemistry. Effects of LOX inhibitors on prostate cancer cell growth were examined by MTT assay, and Hoechst staining was used to determine whether or not the LOX inhibitors induce apoptosis. While 5- and 12-LOX expressions were slightly detected in BPH and NP tissues, marked expressions of 5- and 12-lipoxygenase were detected in PIN and PC tissues. The LOX inhibitors caused marked reduction of prostate cancer cells in a concentration- and time-dependent manner. The LOX inhibitors caused marked inhibition of PC cells through apoptosis. LOX is induced in prostate cancer, and our results suggest that LOX inhibitors may mediate potent antiproliferative effects against prostate cancer cells. Thus, LOX may become a new target in treatment of prostate cancer.

Plasma exchange therapy for the treatment of Escherichia coli O-157 associated hemolytic uremic syndrome.

Plasma exchange (PE) therapy was administered to three patients with Escherichia coli O-157 associated hemolytic uremic syndrome (HUS) in early phase. Following several PE treatments, all cases completely recovered without any apparent complications. The usefulness of PE therapy in removing microbial fragments and inflammatory cytokines was evaluated. The peptidoglycan (PG) level, interleukin-1 receptor antagonist (IL-1Ra) were higher in HUS patients starting PE therapy than in patients who had received several sessions of PE therapy. PE therapy was an effective early phase treatment for Escherichia coli O-157 associated HUS.

Response of peripheral blood mononuclear cells in hemodialyzed patients against endotoxin and muramyldipeptide.

Microbial fragments of endotoxin (ET) and peptidoglycan (PG) are recognized as pyrogen in dialysate. The aim of this study was to evaluate the effect of contaminated dialysate on peripheral blood mononuclear cells (PBMC) in hemodialyzed patients by measuring production of interleukine 1-beta (IL-1beta) in vitro. Venous blood was withdrawn before dialysis session. The effects of a dialysis membrane, a magnitude of dialysate contamination and a duration of hemodialysis were studied. PBMC was stimulated by the addition of water containing either ET or muramyldipeptide (MDP), the minimum biological activated fragment of PG, or ET+MDP. IL-1beta production of PBMC stimulated by ET or ET+MDP in patients on hemodialysis using a polysulfon (PS) membrane was significantly lower than those using a cuprammonium-rayon (CU) membrane, ethylenevinylalcohol (EVAL) membrane, polymethylmetacrylate (PMMA) membrane, respectively. Among patients on the PS membranes, those who were exposed to dialysate with higher pyrogen contamination had lower PBMC cytokine production than those dialyzed with ultrapure dialysate. Response of PBMC in patients against ET+MDP stimulant decreased with duration of dialysis treatment. This suggested that chronic exposure to ET or MDP during hemodialysis treatment, might cause a tolerance against ET and ET+MDP in PBMC.

Direct hemoperfusion by using Lixelle column for the treatment of systemic inflammatory response syndrome.

We have previously reported that Lixelle which was used for beta2-microglobulin (BMG) adsorption column could adsorb not only BMG but also inflammatory cytokines and microbial fragments such as endotoxin (ET) and peptidoglycan (PG). The aim of this study was to estimate that an adsorbent column was used in direct hemoperfusion in patients clinically having systemic inflammatory response syndrome (SIRS), and the relationship between a decrease in cytokines and clinical course was examined. Meanwhile, as regards in vivo rate of removing cytokine based on pre-treatment cytokine concentration versus pre-column concentration at the time of evaluation, it increased with lapse of time, and the removing rate was 40% with 4 h direct hemoperfusion by using the Lixelle column in some of the patients. As to in vivo rates of adsorbing IL-1beta, IL-1Ra, IL-6, IL-8 and TNF-alpha before and after the use of column at the time of evaluation, the rates 5 min after the start were 31.4, 39.3, 36.4, 76.2 and 71.6% respectively. Clinically, it was possible to increase blood pressure and recover from shock status. With the use of this column, removal of inflammatory cytokine by adsorption can be expected. Thus, it can be applied to the treatment of hypercytokinemia.

Percutaneous transluminal angioplasty against arteriosclerosis obliterans in dialysis patients.

The incidence of peripheral arteriosclerosis is on the increase in chronic hemodialysis patients. Recently, the intervention (IV) treatment is conducted to deal with this problem. IV was performed in 4 dialysis patients against the complication of arteriosclerosis obliterans (ASO) but the result was unsuccessful in 3 of them. These 3 failure cases were investigated to find the problems associated with percutaneous transluminal angioplasty (PTA). Cases 1, 2 and 3 had intermittent claudication while case 4 had gangrenous toes as the major complaint. The symptoms in these cases were attributable to 90-100% stenosis and occlusion of superficial femoral artery, bilateral iliac arteries, bilateral superficial femoral-popliteal artery, branch of right iliac artery and left iliac artery region, respectively. IV was successful in case 1 but failed in cases 2 and 4 because the catheter itself did not go through due to the severe stenosis of vessel or the procedure of forcefully dilating the vessel caused dispersion of minute thrombi. In case 3, acute myocardial infarction occurred at 10 h after successful IV, resulting in sudden death. In view of the extent of invasion, IV is a treatment method selected against ASO in dialysis patients. However, the method has a high risk of causing thrombus formation, vessel rupture and organ failure. In this regard, it is advisable to evaluate the systemic condition and conduct IV if the extent of stenosis is mild.

Investigation of endotoxin adsorption with polyether polymer alloy dialysis membranes.

Endotoxin (ET) in the dialysate is known to be adsorbed by dialysis membranes made of polyether polymer alloy (PEPA) and polymethylmethacrylate (PMMA). In the present study, the effect of polyvinylpyrrolidone (PVP) localization of the PEPA dialysis membrane on the adsorption of ET was investigated. The compounding of PVP in the PEPA membrane was changed, and hydrophobic membrane in both blood side and dialysate side, and hydrophilic membrane in only the blood side were used. Adsorption was evaluated by filling the contaminated dialysate inside and outside the membrane after priming with physiological saline, and determining the ET concentration in the blood side and dialysate side of dialysis membrane during the 240 min period from the start of filling the contaminated dialysate. With the PEPA membranes investigated, ET was significantly adsorbed to the hydrophobic side and was not adsorbed to the blood side of hydrophilic type membrane. These results suggest that in addition to electrostatic action attributable to the compounding of hydrophilic agent PVP to the dialysis membrane, the distribution of PVP that was compounded and the potential of the membrane itself may cause differences in adsorption of ET.