-
1.
Adsorption of Protein-Bound Uremic Toxins Through Direct Hemoperfusion With Hexadecyl-Immobilized Cellulose Beads in Patients Undergoing Hemodialysis.
Yamamoto, S, Sato, M, Sato, Y, Wakamatsu, T, Takahashi, Y, Iguchi, A, Omori, K, Suzuki, Y, Ei, I, Kaneko, Y, et al
Artificial organs. 2018;(1):88-93
Abstract
An accumulation of protein-bound uremic toxins (PBUTs) is one of major reasons for development of uremia-related complications. We examined the PBUT removal ability of a hexadecyl-immobilized cellulose bead (HICB)-containing column for patients undergoing hemodialysis. Adsorption of indoxyl sulfate (IS), a representative PBUT, to HICBs was examined in vitro. The HICB column was used in patients undergoing hemodialysis for direct hemoperfusion with a regular hemodialyzer. The serum IS, indole acetic acid (IAA), phenyl sulfate (PhS), and p-cresyl sulfate (PCS) levels were measured before and after passing the column. HICBs adsorbed protein-free (free) IS in a dose- and time-dependent manner in vitro (55.4 ± 1.4% adsorption of 1 millimolar, 251 µg/mL, IS for 1 h). In clinical studies, passing the HICB-containing column decreased the serum level of free IS, IAA, PhS, and PCS levels significantly (by 34.4 ± 30.0%, 34.8 ± 25.4%, 28.4 ± 18.0%, and 34.9 ± 22.1%, respectively), but not protein-bound toxins in maintenance hemodialysis patients. HICBs absorbed some amount of free PBUTs, but the clinical trial to use HICB column did not show effect to reduce serum PBUTs level in hemodialysis patients. Adsorption treatment by means of direct hemoperfusion with regular hemodialysis may become an attractive blood purification treatment to increase PBUT removal when more effective materials to adsorb PBUTs selectively will be developed.
-
2.
[Preparation and clinical application of indomethacin gel for medical treatment of stomatitis].
Momo, K, Shiratsuchi, T, Taguchi, H, Hashizaki, K, Saito, Y, Makimura, M, Ogawa, N
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 2005;(5):433-40
-
-
Free full text
-
Abstract
The preparation and clinical applications of indomethacin (IM) gel were investigated in the treatment of stomatitis resulting from chemotherapy and radiotherapy for cancer. IM gel was prepared by adding various water-soluble polymers [hydroxypropyl cellulose (HPC), etc.] to IM aqueous solution. The release rate of IM from IM gels was found to decrease with increasing polymer concentration and viscosity and to follow a first-order reaction rate equation. The release rate of IM from the IM gel with HPC was decreased gradually with increasing polymer concentration and to be easily controllable compared with gels with other polymers. The time before pain relief occurred after application of the IM gel was slightly shorter and the duration of pain relief was longer compared with the IM aqueous solution. It was confirmed that IM gel is useful in the treatment of stomatitis.
-
3.
Vitamin E-loaded dialyzer resets PBMC-operated cytokine network in dialysis patients.
Libetta, C, Zucchi, M, Gori, E, Sepe, V, Galli, F, Meloni, F, Milanesi, F, Dal Canton, A
Kidney international. 2004;(4):1473-81
-
-
Free full text
-
Abstract
BACKGROUND In hemodialysis patients the activity of stimulated Th1 lymphocytes is depressed, while Th2 cells are constitutively primed. Such phenomena may depend on monocyte activation and altered release of interleukin (IL)-12 and IL-18, which regulate Th cell differentiation. Reactive oxygen species (ROS) activate monocytes; therefore, a hemodialyzer with antioxidant activity would contrast ROS, prevent monocyte activation, reset IL-12 and IL-18 release, and restore Th1/Th2 balance. METHODS Ten patients on regular dialysis treatment (RDT) with cellulosic membrane (CM) were shifted to vitamin E-coated dialyzer (VE). During treatment with CM and after 3, 6, and 12 months of treatment with VE, peripheral blood mononuclear cells (PBMC) and purified CD4+ cells were isolated, and cultured, resting, mitogen-stimulated, and interferon gamma (IFNgamma), IL-4, IL-10, IL-12, and IL-18 release was measured. Vitamin E and A plasma levels and the effects of a single dialysis session on peripheral blood NO levels were assayed. RESULTS The constitutive release of IL-4 and IL-10 by CD4+ cells was abated significantly by treatment with VE (nadir -77.8% and -55.3%, respectively, at 12 months). INFgamma release by mitogen-stimulated CD4+ recovered with VE (zenith +501% at 12 months). PBMC constitutive production of IL-12 and IL-18 was significantly reduced by VE (nadir at 12 months -64.7% and -51.3%, respectively). VE increased plasma levels of vitamins E and A. NO plasma levels fell after a single dialysis treatment with VE (-17%, P < 0.05) in contrast with CU (+27.1%, P < 0.05). CONCLUSION The network of cytokines released by monocytes and Th cells is reset toward normality by treatment with vitamin E-coated dialyzer.
-
4.
Oxidative stress during leukocyte absorption apheresis.
Hirayama, A, Nagase, S, Ueda, A, Ishizu, T, Taru, Y, Yoh, K, Hirayama, K, Kobayashi, M, Koyama, A
Journal of clinical apheresis. 2003;(2):61-6
Abstract
Leukocyte absorption apheresis absorbs leukocytes to the apheresis columns involving leukocyte activation. This process is regarded as bioincompatible and avoided in hemodialysis or other extracorporeal circulation processes. Thus, leukocyte apheresis has a potential risk to exacerbate in vivo oxidative stress. We evaluated the changes in plasma oxidative stress during leukocyte apheresis. Patients diagnosed as ulcerative colitis (UC) and treated with leukocyte apheresis were studied. Adacolumn (celluloseacetate beads) or Cellsorba EX (polyethylenephtarate fiber) was used for the leukocyte absorption device. Oxidative stress was measured by thiobarbituric acid reactive substances (TBARS) and hydroxyl radical ((*)OH) scavenging activity. Plasma samples were collected from the pre- and post-column sampling port at the start, and from the pre-column sampling port at the end of the treatment. The (*)OH signal intensities (OHRI) significantly increased during a column passage, indicating a loss of plasma (*)OH scavenging activity. However, OHRI was reduced at the end, suggesting a recovery of radical scavenging activity during leukocyte apheresis. Significant decreases of OHRI and TBARS were only observed in the early phase of the therapeutic course. No differences of OHRI and TBARS levels were observed between the two columns. These results indicate that though the plasma antioxidant activity was diminished by a column passage, plasma antioxidant activity recovers during the procedure. This efficient antioxidative effect is limited to the early phase of the therapeutic course.
-
5.
Angiogenin: a novel inhibitor of neutrophil lactoferrin release during extracorporeal circulation.
Schmaldienst, S, Oberpichler, A, Tschesche, H, Hörl, WH
Kidney & blood pressure research. 2003;(2):107-12
Abstract
Degranulation of polymorphonuclear leukocytes (PMNL) occurs during extracorporeal circulation. A degranulation-inhibiting protein identical to angiogenin was recently isolated from high-flux dialyzer ultrafiltrate. This protein inhibits the release of lactoferrin and metalloproteinases from PMNL in vitro. In the present study, we investigated end-stage renal disease patients undergoing regular hemodialysis treatment with either high-flux dialyzers (n = 51) or low-flux dialyzers (n = 44), and chronically uremic patients undergoing hemodiafiltration (n = 30). Hemodialysis therapy with low-flux polysulfone or cellulose triacetate membranes caused no or only minimal reduction (≤8%) of plasma angiogenin levels within 2 h of dialysis treatment associated with a 1.6-fold lactoferrin release from PMNL. Hemodialysis therapy with high-flux membranes (e.g. cellulose triacetate, polymethylmethacrylate) or hemodiafiltration resulted in a reduction of plasma angiogenin levels by 20-40% after 2 h associated with a nearly 4-fold PMNL lactoferrin release. The release of PMNL elastase was not affected by the different treatment modalities used. We conclude that high angiogenin plasma levels protect against lactoferrin release from PMNL during extracorporeal circulation in chronically uremic patients. A decrease of plasma angiogenin between 20 and 40% during extracorporeal circulation, however, results in marked PMNL lactoferrin release. This novel mechanism may explain, at least in part, PMNL degranulation also in non complement activating high-flux membranes.
-
6.
Oxidative stress and erythrocyte integrity in end-stage renal failure patients hemodialysed using a vitamin E-modified membrane.
Westhuyzen, J, Saltissi, D, Stanbury, V
Annals of clinical and laboratory science. 2003;(1):3-10
Abstract
Oxidative stress has been implicated in a range of disease states, including end-stage renal failure treated with hemodialysis. Hemodialysis with vitamin E-modified membranes reduces lipid peroxidation, but the effect on erythrocyte integrity has not been determined. This study compared antioxidant defense parameters and the resistance of erythrocytes to free radical-mediated hemolysis in patients dialysed with cellulose acetate membranes at baseline and with a vitamin E-modified membrane (Excebrane Clirans; Terumo Corporation) for 13 wk. Resistance of erythrocytes to free radical attack was assessed in vitro using the peroxyl hemolysis test. The time to 50% hemolysis (T50%) increased significantly during the first 6 wk of Excebrane use (p < 0.05), but this parameter returned to baseline by 13 wk. Glutathione concentration and erythrocyte superoxide dismutase activity were unchanged during the study, but glutathione peroxidase activity increased from low levels at baseline and became significantly higher at 6 and 13 wk (p < 0.001). Total erythrocyte polyunsaturated fatty acid content and C18:2 level increased (p < 0.001) and saturated fatty acids (total, C16:0, C18:0, C22:0 and C24:0) decreased (p < 0.03). Total monounsaturated fatty acid content was unchanged. The increased resistance of erythrocytes to hemolysis, the increased glutathione peroxidase activity, and the increased degree of unsaturation of fatty acids in the erythrocyte membrane are compatible with a reduction of oxidative stress during hemodialysis with vitamin E-modified membranes.
-
7.
Nasal glucagon delivery using microcrystalline cellulose in healthy volunteers.
Teshima, D, Yamauchi, A, Makino, K, Kataoka, Y, Arita, Y, Nawata, H, Oishi, R
International journal of pharmaceutics. 2002;(1-2):61-6
Abstract
We developed an intranasal powder form of glucagon to improve metabolic status and fatty liver in patients with pancreatectomy. Microcrystalline cellulose, which is commonly used in commercial preparations for allergic rhinitis was used as an absorption enhancer. We compared the intranasal powder form with some spray solutions of glucagon with regard to glucagon absorption, concentration of blood glucose, stability and nasal irritation. The absorption of glucagon from the spray solution including 1.5% sodium glycocholate or 1% sodium caprate was 1.3- and 2.6-fold higher than that from the powder form mixed with microcrystalline cellulose at a ratio of 1:69, respectively. The C(max) values of plasma glucose were 2.18, 3.39 and 1.56 mmol l(-1) in the spray solutions including sodium glycocholate and sodium caprate and in the powder form, respectively. However, glucagon in spray solutions was unstable, but that in the powder form was stable at 5 and 25 degrees C for at least 84 days. The spray solution caused strong irritation, but the powder form did not. These results suggested usefulness of the powder form of glucagon for treatment of pancreatectomized patients.
-
8.
Changes of serum albumin and C-reactive protein are related to changes of interleukin-6 release by peripheral blood mononuclear cells in hemodialysis patients treated with different membranes.
Memoli, B, Minutolo, R, Bisesti, V, Postiglione, L, Conti, A, Marzano, L, Capuano, A, Andreucci, M, Balletta, MM, Guida, B, et al
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2002;(2):266-73
Abstract
Protein malnutrition, a condition associated with an albumin concentration less than 3.5 g/dL, has been shown to be a major risk factor for increased mortality in hemodialysis patients. The aim of this cross-over study was to evaluate the relationship between the type of membrane adopted and serum albumin changes by measuring peripheral blood mononuclear cells (PBMC) interleukin-6 (IL-6) release, serum albumin, and plasma concentrations of C-reactive protein (CRP) in 18 patients dialyzed with different membranes. During the study, all patients were dialyzed with cuprophan (CU), synthetically modified cellulosic (SMC) membrane (a new cellulosic membrane with lesser complement activation), and cellulose diacetate (CD) membrane, and have served as their own controls. IL-6 spontaneous release by PBMC resulted after 3 months of SMC (436.2 +/- 47.4 pg/mL) significantly (P < 0.05) reduced as compared with CU (569.3 +/- 24.5 pg/mL). This effect was more evident after 6 months of dialysis with SMC (220 +/- 35.3 pg/mL, P < 0.01 versus CU and versus 3 months of SMC). The passage to CD membrane was followed by a progressive new increase in the IL-6 PBMC release (332.3 +/- 30.7 after 3 months, and 351.2 +/- 35.8 pg/mL after 6 months, respectively) that, however, remained significantly (P < 0.05) lower than CU. The behavior of CRP plasma levels resembled that of IL-6 PBMC release (23.3 +/- 4.7 in CU, 11.0 +/- 2.1 after 3 months in SMC, and 7.9 +/- 1.5 after 6 months in SMC, respectively). IL-6 release values were positively correlated with circulating levels of CRP (r = 0.3264, P < 0.002). Serum albumin increased after 6 months of dialysis with SMC membranes (3.25 +/- 0.09 g/dL in CU and 3.64 +/- 0.07 g/dL in SMC, P < 0.05). When the patients were switched to CD, serum albumin showed a slight, though not statistically significant, decrease. Serum albumin concentrations negatively correlated with both IL-6 release values (r = -0.247, P < 0.05) and CRP plasma levels (r = -0.433, P < 0.001). In conclusion, our data clearly show that a significant relationship exists between biocompatibility of the membranes and serum albumin changes; serum albumin levels, in fact, are negatively correlated with the PBMC spontaneous IL-6 release values and CRP circulating levels.
-
9.
[Beneficial effect of AN69 membranes on anemia in hemodialyzed patients].
García Cortés, MJ, Sánchez Perales, MC, Liébana, A, Gil, JM, Borrego, FJ, Borrego, J, Pérez del Barrio, P, Serrano, P, Pérez Bañasco, V
Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia. 2001;(4):370-5
Abstract
UNLABELLED Biocompatible hemodialysis membranes induce a smaller inflammatory response in hemodialysis patients, and remove a larger amount of higher molecular weight retention products, then cellulose membranes. These phenomena could improve uremic anemia in hemodialysis patients. The objective was to evaluate the effects of biocompatible AN69 membranes on anemia in hemodialysis patients. Twenty-five stable patients undergoing hemodialysis with cuprophane membrane for more than 6 months were studied prospectively. These patients were stratified in 2 groups. Group I (GI): 14 patients switched over to a more biocompatible dialyzer (from cuprophan to AN69) and Group II (GII): 11 patients continued treatment with the same cuprophan membrane. The study lasted 5 months. Baseline hematocrit (%), ferritin (ng/mL), transferrin saturation (%), KTV, PCR (g/kg/day) and dose of erythropoietin (EPO) (UI/week) were measured and were revised monthly. Target hematocrit was 33%-35%. A significant increase of hematocrit became obvious after 2 months in GI without changes in dose of EPO and intensity of dialysis, meanwhile GII remains stable. CONCLUSION Hemodialysis using AN69 membranes increases hematocrit without modifying intensity of dialysis.