Facile Synthesis of Novel Short-Chain Ligand-Capped Colloidal Metal Oxide Nanoparticles for Printed Flexible Devices.

Colloidal metal oxide nanoparticles are key materials for achieving cost-effective and large-scale production of flexible devices, as they enable the formation of functional oxide thin films at low temperatures (<400 °C) through printing techniques such as inkjet printing, gravure coating, and microcontact printing. The conventional solvothermal synthesis of colloidal metal oxide nanoparticles through the thermal decomposition of precursors results in particles with bulky, long-chain ligands on their surfaces, which hinder the formation of dense oxide films when depositing the colloidal metal oxide nanoparticles. Herein, we have developed a simple and versatile method for synthesizing colloidal metal oxide nanoparticles using base-induced hydrolysis and the condensation of metal acetates as precursors. Various binary and ternary colloidal metal oxide nanoparticles (CuO, Mn3O4, Co3O4, CeO2, In2O3, Co1.8Mn1.2O4) were synthesized using short-chain acetate ligands on their surfaces. The thin acetate ligand-containing colloidal Co1.8Mn1.2O4 nanoparticle film exhibited lower resistivity than the same with long-chain oleate ligands. The films coated onto a polyimide substrate formed a flexible negative temperature coefficient thermistor that exhibited the temperature dependence of resistance comparable to bulk materials with a bending durability of up to 5 mm radius. These findings highlight the effectiveness of utilizing colloidal metal oxide nanoparticles with short-chain ligands in flexible devices.

A new method for the preparation of a purified glucosylceramide and ceramide from shiitake mushroom.

Ingestion of plant and fungal glucosylceramides is known to reduce colon carcinogenesis and skin barrier damage in mice and humans. However, such effects in animal experiments have not been revealed for plant and fungal ceramides because the content of ceramides contained in plants and fungi is so low that the large amount required for animal experiments is difficult to obtain. Noting that the fungus shiitake mushroom (Lentinula edodes) is rich in a glucosylceramide, (4E,8E)-N-d-2'-hydroxypalmitoyl-1-O-ß-d-glucopyranosyl-9-methyl-4,8-sphingadienine [Glc-d19:2(4E,8E,9Me)-h16:0], we developed a new method to purify this fungal glucosylceramide using ethanol precipitation and high-performance liquid chromatography. We also developed a new method to produce large amounts of a ceramide [d19:2(4E,8E,9Me)-h16:0] from this purified glucosylceramide using human glycoside hydrolase family 30 glucocerebrosidase (imiglucerase). These methods will be useful for elucidating the physiological function by ingestion of fungal ceramides in animal experiments.

The Prognostic Impact of Hospital Transfer after Admission due to Acute Heart Failure.

The prognostic impact of transfer to another hospital among acute heart failure (AHF) patients has not been well elucidated.Of the 800 AHF patients analyzed, 682 patients were enrolled in this study for analysis. The subjects were divided into two groups according to their discharge location: discharge home (Group-H, n = 589) or transfer to another hospital for rehabilitation (Group-T, n = 93). The Kaplan-Meier curves revealed a poorer prognosis, including all-cause death and heart failure (HF) events (death, readmission-HF), in Group-T than that in Group-H (P < 0.001, respectively). A multivariate Cox regression model showed that Group-T was an independent predictor of 365-day all-cause death (hazard ratio: 2.618, 95% confidence interval [CI]: 1.510-4.538, P = 0.001). The multivariate logistic regression analysis showed that aging (per 1-year-old increase, odds ratio [OR]: 1.056, 95% CI: 1.028-1.085, P < 0.001), female gender (OR: 2.128, 95% CI: 1.287-3.521, P = 0.003), endotracheal intubation during hospitalization (OR: 2.074, 95% CI: 1.093-3.936, P = 0.026), and increased Controlling Nutritional Status score on admission (per 1.0-point increase, OR: 1.247, 95% CI: 1.131-1.475, P < 0.001) were associated with transfer to another hospital after AHF admission. The prognosis, including all-cause death, was determined to be significantly poorer in patients who were transferred to another hospital, as their activities of daily living were noted to lessen before discharge (n = 11) compared to others (n = 82).Elderly AHF patients suffering from malnutrition were difficult to discharge home after AHF admission, and transfer to another hospital only led to adverse outcomes. Appropriate rehabilitation during definitive hospitalization appears necessary for managing elderly patients in the HF pandemic era.

Successful Treatment of Thrombocytopenia, Anasarca, Fever, Reticulin Myelofibrosis/Renal Insufficiency, and Organomegaly Syndrome Using Plasma Exchange Followed by Rituximab in the Intensive Care Unit.

Thrombocytopenia, anasarca, fever, reticulin myelofibrosis/renal insufficiency, and organomegaly (TAFRO) syndrome is treated using corticosteroids and/or immunosuppressive agents as first-line therapy. We report the case of a 69-year-old female with TAFRO syndrome in which the patient presented multiple organ failure and steroid resistance, which was successfully treated using plasma exchange (PE) followed by rituximab. Decisions regarding the next treatment, including PE, are urgent for patients with steroid-resistant TAFRO syndrome. Since it is considered that immunosuppressive agents may be removed by PE, the performance of PE before treatment with immunosuppressive agents might be an option for steroid-resistant TAFRO syndrome.

Clinical significance of the N-terminal pro-brain natriuretic peptide and B-type natriuretic peptide ratio in the acute phase of acute heart failure.

AIMS: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) levels are rarely evaluated simultaneously in the acute phase of acute heart failure (AHF). METHOD AND RESULTS: A total of 1207 AHF patients were enrolled, and 1002 patients were analysed. Blood samples were collected within 15 min of admission. Patients were divided into two groups according to the median value of the NT-proBNP/BNP ratio [low-NT-proBNP/BNP group (Group L) vs. high-NT-proBNP/BNP group (Group H)]. A multivariate logistic regression model showed that the C-reactive protein level (per 1-mg/dL increase), Controlling Nutrition Status score (per 1-point increase), and estimated glomerular filtration rate (eGFR, per 10-mL/min/1.73 m2 increase) were independently associated with Group H [odds ratio (OR) 1.049, 95% confidence interval (CI) 1.009-1.090, OR 1.219, 95% CI 1.140-1.304, and OR 1.543, 95% CI 1.401-1.698, respectively]. A Kaplan-Meier curve analysis showed that the prognosis was significantly poorer in Group H than in Group L, and a multivariate Cox regression model revealed Group H to be an independent predictor of 180-day mortality [hazard ratio (HR) 3.084, 95% CI 1.838-5.175] and HF events (HR 1.963, 95% CI 1.340-2.876). The same trend in the prognostic impact was significantly observed in the low-BNP (<810 pg/mL, n = 501), high-BNP (≥810 pg/mL, n = 501), and low-eGFR (<60 mL/min/1.73 m2, n = 765) cohorts, and tended to be observed in normal-eGFR (≥60 mL/min/1.73 m2, n = 237) cohort. CONCLUSION: A high NT-proBNP/BNP ratio was associated with a non-cardiac condition (e.g. inflammatory reaction, nutritional status, and renal dysfunction) and is independently associated with adverse outcomes in AHF.

Clinical Significance of the Fibrosis-4 Index in Patients with Acute Heart Failure Requiring Intensive Care.

The Fibrosis-4 (FIB4) index could indicate the liver fibrosis in patients with chronic hepatic diseases. It was calculated using the following formula: (age × aspartate aminotransferase [U/L]) / (platelet count [103/µL] × âˆšalanine aminotransferase [U/L]). However, the clinical impact of the FIB4 index in the acute phase of acute heart failure (AHF) has not been sufficiently investigated.A total 1,468 AHF patients were analyzed. The median FIB4 index was 2.71 [1.85-4.22]. The patients were divided into three groups according to the quartiles of their FIB4 index (low-FIB4 [Q1, ≤ 1.847], middle-FIB4 [Q2/Q3, 1.848-4.216], and high-FIB4 [Q4, ≥ 4.216] groups). A Kaplan-Meier curve analysis showed that the prognosis, such as all-cause mortality and HF events within 365 days, was significantly poorer in the high-FIB4 group than in the middle-FIB4 and low-FIB4 groups. A multivariate Cox regression model identified high FIB4 index as an independent predictor of 365-day all-cause death (hazard ratio (HR): 1.660, 95% CI: 1.136-2.427) and HF events (HR: 1.505, 95% CI: 1.145-1.978). The multivariate logistic regression analysis showed that the high plasma volume status (PVS) (Q4, odds ratio [OR]: 2.099, 95% CI: 1.429-3.082), low systolic blood pressure (SBP) (< 100 mmHg, OR: 3.825, 95% CI: 2.504-5.840), and low left ventricular ejection fraction (< 40%, OR: 1.321, 95% CI: 1.002-1.741) were associated with a high FIB4 index.A high FIB4 index can predict adverse outcomes in AHF patients, which indicate that congestive liver and liver hypoperfusion occur due to low cardiac output in the acute phase of AHF.

The prognostic impact of the serum heart-type fatty acid-binding protein level in patients with sepsis who were admitted to the non-surgical intensive-care unit.

Ongoing myocardial damage at the acme of the sepsis status has not been sufficiently evaluated. The clinical data of 160 sepsis patients who require intensive care and 127 outpatients with chronic heart failure (HF) were compared as a retrospective cohort study. Thereafter, the sepsis patients were divided into 3 groups according to the serum heart-type fatty acid-binding protein (H-FABP) quartiles [low H-FABP = Q1 (n = 39), middle H-FABP = Q2/Q3 (n = 81), and high H-FABP = Q4 group (n = 40)]. The H-FABP level was measured within 15 min of admission. The serum H-FABP levels in the sepsis patients [26.6 (9.3-79.0) ng/ml] were significantly higher than in the choric HF patients [6.6 (4.6-9.7) ng/ml]. A Kaplan-Meier curve showed that the survival rate of the high-H-FABP group was significantly lower than that of the middle- and low-H-FABP groups. The multivariate Cox regression analysis for the 365-day mortality showed that the high-H-FABP group (hazard ratio: 6.544, 95% confidence interval [CI] 2.026-21.140; p = 0.002) was an independent predictor of the 365-day mortality. The same trend in the prognostic impact was significantly (p = 0.015) observed in the cohort that had not been suffering from the cardiac disease before admission. The serum H-FABP level was an independent predictor of the 365-day mortality in the patients who were emergently hospitalized in the intensive-care unit due to sepsis. Ongoing myocardial damage was detected in the majority of patients with sepsis, suggesting that ongoing myocardial damage might be a candidate predictor of adverse outcomes in sepsis patients.

Association of adipocytokines with peritoneal function.

BACKGROUND: Preservation of peritoneal function is crucial for the continuation of peritoneal dialysis (PD). A previous study suggested that blood cholesterol is involved in the preservation of peritoneal function; therefore, we determined whether adipocytokines can predict peritoneal function preservation. METHODS: Eighty patients were enrolled. Serum adiponectin, leptin, apelin, various blood components, and estimated glomerular filtration rate (eGFR) (mL/min/m2) were measured. In addition, the duration of PD, presence or absence of peritonitis and diabetes mellitus, body mass index, urine output, peritoneal Kt/V, renal Kt/V, weekly Kt/V, peritoneal creatinine clearance rate (CCr), renal CCr, weekly CCr, use or nonuse of statin products, dialysate volume, glucose exposure, and use or nonuse of icodextrin dialysate were assessed. Peritoneal equilibration tests were performed at 6-month intervals, and dialysate-to-plasma [D/P] ratio and glucose uptake ratio [D/D0] were measured. Associations of the baseline values and their percent changes with various adipocytokines and test items were evaluated. RESULTS: Multiple regression analyses identified adiponectin (p = 0.0392, p = 0.0348) as a significant predictive factor of D/P and D/D0 ratios. eGFR was identified as a significant predictive factor (p = 0.015) of percent change in the D/P ratio. Apelin (p = 0.0484), high-density lipoprotein cholesterol (p = 0.0066), dialysate volume (p = 0.0223), and urine output (p = 0.0020) were identified as factors affecting the duration of PD. CONCLUSIONS: Adipocytokines are a predictive factor of peritoneal function and the duration of PD in patients undergoing PD.

Time-dependent changes in plasma xanthine oxidoreductase during hospitalization of acute heart failure.

AIMS: The aim of present study is to evaluate the clinical significance of the time-dependent changes in xanthine oxidoreductase (XOR) activity during hospitalization for acute heart failure (AHF). METHODS AND RESULTS: A total of 229 AHF patients who visited to emergency room were prospectively enrolled, and 187 patients were analysed. Blood samples were collected within 15 min of admission (Day 1), after 48-72 h (Day 3), and between Days 7 and 21 (Day 14). The AHF patients were divided into two groups according to the XOR activity on Day 1: the high-XOR group (≥100 pmol/h/mL, n = 85) and the low-XOR group (<100 pmol/h/mL, n = 102). The high-XOR patients were assigned to two groups according to the rate of change in XOR from Day 1 to Day 14: the decreased group (≥50% decrease; n = 70) and the non-decreased group (<50% decrease; n = 15). The plasma XOR activity significantly decreased on Days 3 and 14 [23.6 (9.1 to 63.1) pmol/h/mL and 32.5 (10.2 to 87.8) pmol/h/mL, respectively] in comparison with Day 1 [78.5 (16.9 to 340.5) pmol/h/mL]. A Kaplan-Meier curve indicated that the prognosis, including heart failure (HF) events (all-cause death and readmission by HF) within 365 days, was significantly poorer in the low-XOR patients than in the high-XOR patients and was also significantly poorer in the non-decreased group than in the decreased group. CONCLUSIONS: The plasma XOR activity was rapidly decreased by the appropriate treatment of AHF. Although high-XOR activity on admission was not associated with increased HF events in AHF, high-XOR activity that was not sufficiently reduced during appropriate treatment was associated with increased HF events.

JPH203, a newly developed anti-cancer drug, shows a preincubation inhibitory effect on L-type amino acid transporter 1 function.

JPH203 is a novel anti-cancer drug targeting L-type amino acid transporter 1 (LAT1), which plays a primary role in the uptake of essential amino acids in tumor cells. Although a co-incubation inhibitory effect of JPH203 has been shown in a conventional uptake assay, its preincubation inhibitory effects have remained undetermined. Therefore, we aimed to characterize the preincubation inhibitory effects of JPH203 on LAT1 function using leucine uptake assays in LAT1-positive human colon cancer HT-29 cells. Preincubation of the cells with JPH203 (0.3 µM for 120 min) decreased the activity level to 30% of that in dimethylsulfoxide-treated cells. Similarly, in time-dependency analysis, preincubation of HT-29 cells with 10 µM JPH203 for 30, 60, and 120 min decreased the leucine uptake activity (42%, 32%, and 28% of that in control cells, respectively). Furthermore, the IC50 value of the combination of preincubation and co-incubation effects was lower than that of co-incubation inhibition alone (34.2 ± 3.6 nM vs. 99.2 ± 11.0 nM). In conclusion, we revealed that JPH203 has the capability to inhibit LAT1 function through preincubation effects. Moreover, preincubation synergistically enhances the co-incubation inhibitory effects. These findings provide a novel insight into the anti-cancer effects of JPH203 in cancer therapy.

Importance of the Corrected Calcium Level in Patients With Acute Heart Failure Requiring Intensive Care.

Background: Serum calcium (Ca) concentrations in the acute phase of acute heart failure (AHF) have not been not sufficiently investigated. Methods and Results: This study enrolled 1,291 AHF patients and divided them into 3 groups based on original and corrected Ca concentrations: (1) hypocalcemia (both original and corrected Ca ≤8.7 mg/dL; n=651); (2) pseudo-hypocalcemia (original and corrected Ca ≤8.7 and >8.7 mg/dL, respectively; n=300); and (3) normal/hypercalcemia (both original and corrected Ca >8.7 mg/dL; n=340). AHF patients were also divided into 2 groups based on corrected Ca concentrations: (1) corrected hypocalcemia (corrected Ca ≤8.7 mg/dL; n=651); and (2) corrected normal/hypercalcemia (corrected Ca >8.7 mg/dL; n=640). Of the 951 patients with original hypocalcemia (≤8.7 mg/dL), 300 (31.5%) were classified as corrected normal/hypercalcemia after correction of Ca concentrations by serum albumin. The prognoses in the pseudo-hypocalcemia, low albumin, and corrected normal/hypercalcemia groups, including all-cause death within 730 days, were significantly poorer than in the other groups. Multivariate Cox regression analysis showed that classification into the pseudo-hypocalcemia, hypoalbumin, and corrected normal/hypercalcemia groups independently predicted 730-day all-cause death (hazard ratios [95% confidence intervals] of 1.497 [1.153-1.943], 2.392 [1.664-3.437], and 1.294 [1.009-1.659], respectively). Conclusions: Corrected normal/hypercalcemia was an independent predictor of prognosis because this group included patients with pseudo-hypocalcemia, which was affected by the serum albumin concentration.

Sodium-coupled monocarboxylate transporter 1 interacts with the RING finger- and PDZ domain-containing protein PDZRN3.

Sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8) mediates monocarboxylate transport in the proximal tubule of the kidney. We have identified PDZK1 and PDZ domain-containing RING finger 3 (PDZRN3) as potent binding partners of SMCT1, which has a PDZ motif (Thr-Arg-Leu), by yeast two-hybrid screening and revealed that PDZK1 enhances the transport activity of SMCT1. In this study, we aimed to characterize the interaction between SMCT1 and PDZRN3 as well as to examine how PDZRN3 regulates SMCT1 function. An interaction between SMCT1 and PDZRN3 through the PDZ motif was observed in a co-immunoprecipitation assay and yeast two-hybrid assay. A transport assay showed that PDZRN3 abolished the enhancing effect of PDZK1 on nicotinate uptake via SMCT1. Our results suggest that SMCT1 interacts with PDZRN3 and that PDZRN3 may regulate SMCT1 function by interfering with the interaction between SMCT1 and PDZK1.

Current Practice and Outcomes of Peritoneal Dialysis in the Nippon Medical School Musashi Kosugi Hospital.

INTRODUCTION: Various innovations for preventing complications and improving a patient's quality of life have been implemented for peritoneal dialysis (PD), which was established in Japan approximately 35 years ago and introduced at our hospital in 1999. Herein, we investigate the outcomes of patients undergoing PD to identify approaches for improving their long-term prognosis. METHODS: This retrospective study included 114 patients who underwent PD between September 1999 and August 2017 and included various parameters such as patient survival rate, technical survival rate, cause (s) of PD withdrawal, incidence of peritonitis, dialysis duration, and change in residual renal function (RRF). Furthermore, factors associated with PD withdrawal and duration, as well as risk factors for peritonitis, were examined. RESULTS: Mean (± standard deviation) PD duration was 35.62 (±29.88) months in all patients and 37.16 (±34.09) months in 58 patients who withdrew from treatment. Five-year continuance and survival rates were 40.41% and 55.74%, respectively (p=0.0061). However, in patients aged ≥65 years, the continuance and survival rates were not significantly different (p=0.1250). Furthermore, the continuance and survival rates in diabetic patients were not significantly different from those of non-diabetic patients (p=0.1334 and 0.7140, respectively). Comparison of changes in RRF in young and elderly patients revealed that it was not significantly sustained in elderly patients (p=0.0259). The Cox proportional hazards model revealed that age (p=0.0455) and total cholesterol levels (p=0.0494) were independent risk factors for PD withdrawal, and multiple regression analysis showed that the presence of peritonitis (p=0.0063) and low-density lipoprotein cholesterol (LDL-C) levels (p=0.0087) were significant factors for PD duration. Peritonitis incidence was 0.077 times per patient per year, and multivariate analysis identified PD duration (p=0.0009) and LDL-C levels (p=0.0054) as independent risk factors for peritonitis. CONCLUSION: The findings of this study revealed that assessment of the nutritional status of the patient and prevention of peritonitis are important for continuation of PD. PD is a safe treatment option that can maintain the quality of life in elderly patients. In a rapidly aging society, the need for PD-based medical care is expected to increase.

The uricosuric effects of dihydropyridine calcium channel blockers in vivo using urate under-excretion animal models.

The purpose of this study was to create novel urate under-excretion animal models using pyrazinamide and to evaluate whether dihydropyridine calcium channel blockers (CCBs) have uricosuric effects in vivo. Adult male ICR mice were treated with pyrazinamide, vehicle (dimethyl sulfoxide: DMSO), or tap water. Thirty minutes later, pyrazinamide-treated mice were given benzbromarone, losartan, nilvadipine, nitrendipine, nifedipine or azelnidipine. Six hours after the second administration, urine (by urinary bladder puncture) and plasma were collected to measure uric acid and creatinine levels, and fractional excretion of uric acid (FEUA) and creatinine clearance (Ccr) were calculated and evaluated. There was no significant difference in the levels of plasma uric acid, plasma creatinine, Ccr, urinary N-acetyl-ß-d-glucosaminidase (NAG) and urinary NAG-creatinine ratio between water, DMSO, and pyrazinamide-treated mice. But the FEUA of pyrazinamide-treated mice was significantly lower than water mice. The FEUA was significantly higher in mice taking the dihydropyridine CCBs (nilvadipine, nitrendipine, nifedipine, and high-dose azelnidipine) than in pyrazinamide-treated mice. There was no significant difference in Ccr. Thus, a novel animal model created with PZA administration was useful as a urate under-excretion animal model that was probably URAT1-mediated, and the uricosuric effects of dihydropyridine CCBs were confirmed in vivo.

Characterization of an L-Carnitine Transport System in Murine Photoreceptor Cell Line.

While it is well known that L-carnitine [3-hydroxy-4-(trimethylazaniumyl)-butanoate] is an essential molecule for ß-oxidation, it provides anti-oxidative effects as well. Since these effects have been observed in photoreceptor cells, the carnitine's intracellular concentration is considered to play a protective role against oxidative damage to those cells. However, even though its high hydrophilicity makes it likely that carnitine import is accomplished via a dedicated host transport system, the specific uptake process into those cells is currently unknown. Therefore, in this study, we sought to identify and characterize photoreceptor cell carnitine uptake transporter(s) utilizing 661W cells as a photoreceptor cell model. The results of our uptake assays showed that carnitine was transported into 661W cells in a saturable manner (Km=5.5 mM), and that the activity was susceptible to extracellular pH and Na+. While these data suggest the involvement of a transporter in 661W cell carnitine uptake, the observed transport profile did not correspond to any of the currently known carnitine transporters such as organic cation/carnitine transporter 1 (Octn1), Octn2, Octn3, B0,+ and Ct2. In fact, in our experiments, the mRNA expressions for such carnitine transporters in 661W cells were consistently very low and the carnitine transporter substrates did not inhibit the uptake activities. Taken as a whole, our results indicate that carnitine is transported into 661W cells in a carrier-mediated manner. However, since its transport modes cannot be fully explained by known carnitine transporters, it is highly likely that photoreceptor cells utilize a unique molecularly-based carnitine uptake system.

[Prisoners' reasons for confessions and interviewing styles].

This study examined the relationships between the reasons for confessions and interviewing styles by administering a self-reported questionnaire to new male adult prison inmates across Japan. The three factors proposed by Gudjonsson and his colleagues (1991, 1992, 1994, 1999), namely, perception of proof, internal pressure, and external pressure, were investigated. When participants had decided to confess prior to interviews, they were more likely to confess due to perception of proof and internal pressure compared to their counterparts. Furthermore, participants who experienced a relationship-focused interviewing style, which stressed active listening and rapport-building while talking about the criminal incidents directly, were more likely to confess due to internal pressure and less likely to confess due to external pressure.

[Linkage analysis of serial sex crimes].

The purpose of this study was twofold: first, to create an index for a behavioral linkage analysis of serial sex crimes, and second, to construct a predictive model for the analysis. Data on 720 sex crimes (rape, indecent assault) committed by 360 offenders arrested between 1993 and 2005 throughout Japan were collected. The following seven behaviors were examined during a series of analyses aimed at illustrating the effectiveness of crime linkage in serial sex crimes: victim age group, area type, publicness of offense site, weapon, time, contact method, and day of the week. The results indicated that six of the seven behaviors (excluding "day of the week") significantly distinguished between linked and unlinked crime pairs. Under a logistic regression of these six variables, which were dichotomously coded in terms of the concordance or discordance between each pair of incidents, the area under the receiver operating characteristic (ROC) curve was 0.85 (95% CI = 0.82-0.87), indicating a high level of discriminative accuracy in identifying disparate sex crimes committed by the same person.

Comparison of pain and efficacy of darbepoetin alfa and epoetin Beta pegol treatment in patients receiving peritoneal dialysis.

BACKGROUND: Sustained erythropoiesis-stimulating agents (ESAs) have recently been identified as the standard therapeutic agent for anemia in patients undergoing peritoneal dialysis (PD). However, few reports have compared pain between various types of sustained ESAs or between administration routes. Furthermore, the change ratio of the dose of sustained ESAs reportedly ranges from 0.8 to 1.3. In the present study, to compare darbepoetin alfa and epoetin beta pegol (a continuous erythropoietin receptor activator [CERA]), we examined the dolorific differences between administration routes and the effect on anemia by using a chjange ratio of 0.8 with darbepoetin alfa in patients with renal anemia undergoing PD. SUBJECTS AND METHOD: We randomly assigned 20 patients with stable hemoglobin levels undergoing PD to either a darbepoetin alfa therapy group or a CERA therapy group. Based on a previous report, the change ratio of the CERA group from CERA to darbepoetin alfa therapy was assumed to be 0.8, and therapy was crossed-over to darbepoetin alfa again 2 months later. The dolorific evaluation (pain measurement) used both a face scale and a visual analogue scale. We compared the agents as well as administration routes with respect to pain. We also measured variables related to anemia and iron metabolism. RESULTS: The change ratio of the CERA group at the start of the study was 0.821. On resumption of darbepoetin alfa therapy 2 months later, the doses of darbepoetin alfa increased. The darbepoetin alfa group showed a stronger tendency for pain, although the difference was not significant. In contrast, subcutaneous administration in the CERA group showed significant pain just after injection. The CERA group, however, showed a significant decrease in hemoglobin levels after 2 months of treatment (p=0.0489). No significant change was found in the hematocrit or the reticulocyte count. There were no significant differences in iron metabolism, as shown by serum iron levels and total iron-binding capacity, in either group. However, serum ferritin levels showed a tendency to decrease in the darbepoetin alfa group. CONCLUSION: No significant difference in pain was found between darbepoetin alfa and CERA therapies, but a significant difference in pain was noted between administration routes, just after injection, in the CERA group. The results also suggest that a change ratio of 0.8 from darbepoetin alfa to CERA is low for managing anemia.

Effects of alogliptin in chronic kidney disease patients with type 2 diabetes.

OBJECTIVE: Diabetes is a major risk factor for chronic kidney disease (CKD). In this study, we examined the effects of alogliptin on blood glucose control and the renal function in type 2 diabetes CKD patients. METHODS: We recruited 36 CKD patients with type 2 diabetes. The patients were followed up for six months after adding alogliptin. Blood biochemical, urine test and office BP values were obtained six months before and after the start of treatment. RESULTS: The mean HbA1c value was not decreased; however, the 1,5-AG values tended to improve (p=0.1023). The mean eGFR was unchanged. There were no significant changes in the patients with an eGFR of 60 mL/min/1.73 m2 or more (25 patients) or in the patients with an eGFR less than 60 mL/min/1.73 m2 (11 patients). A total of 15 patients were identified to have rapidly declining diabetic nephropathy, with an annual reduction in eGFR of 5 mL/min/1.73 m2 or more. The slope of the regression line for eGFR (-1.296 before starting treatment with alogliptin) was positive, increasing up to 0.08786. The eGFR values appeared to stop decreasing and positively reversed. The urinary albumin-to-creatinine ratio exhibited a downward trend. The effect on the renal function was independent of the levels of blood sugar, blood pressure and lipids. CONCLUSION: We examined the ability of alogliptin to maintain the renal function in patients with CKD complicated by type 2 diabetes. Our study suggests that alogliptin can be safely administered in patients with CKD. However, although we expected alogliptin to demonstrate renal protective effects, were unable to detect statistically significant differences. One reason for this finding is that there are few registered cases.