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Summary: 5′-Adenosine monophosphate-activated protein kinase (AMPK) is a potential therapeutic target for various medical conditions. We here identify a small-molecule compound (RX-375) that activates AMPK and inhibits fatty acid synthesis in cultured human hepatocytes. RX-375 does not bind to AMPK but interacts with prohibitins (PHB1 and PHB2), which were found to form a complex with AMPK. RX-375 induced dissociation of this complex, and PHBs knockdown resulted in AMPK activation, in the cultured cells. Administration of RX-375 to obese mice activated AMPK and ameliorated steatosis in the liver. High-throughput screening based on disruption of the AMPK-PHB interaction identified a second small-molecule compound that activates AMPK, confirming the importance of this interaction in the regulation of AMPK. Our results thus indicate that PHBs are previously unrecognized negative regulators of AMPK, and that compounds that prevent the AMPK-PHB interaction constitute a class of AMPK activator.

Abstract Background This article is a duplicated publication from the Japanese version of “2019 JSDT Guidelines for Peritoneal Dialysis” with permission from the Japanese Society for Dialysis Therapy (JSDT). This clinical practice guideline (CPG) was developed primarily by the Working Group on Revision of Peritoneal Dialysis (PD) Guidelines of the Japanese Society for Dialysis Therapy. Recently, the definition and creation process for CPGs have become far more rigorous; traditional methods and formats no longer adhere to current standards. To improve the reliability of international transmission of our findings, CPGs are created in compliance with the methodologies developed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group. Part 2 of this PD guideline is the first CPG developed by our society that conforms to the GRADE approach. Methods Detailed processes were created in accordance with the Cochrane handbook and the GRADE approach developed by the GRADE working group. Results Clinical question (CQ)1: Is the use of renin-angiotensin system inhibitors (RAS inhibitors), such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), effective in PD patients? Recommendation: We suggest the usage of RAS inhibitors (ACEI and ARB) in PD patients (GRADE 2C). CQ2: Icodextrin or glucose solution: which is more useful as a dialysate among patients with PD? Recommendation: We suggest using icodextrin when managing body fluids in PD patients (GRADE 2C). CQ3: Is it better to apply or not apply mupirocin/gentamicin ointment to the exit site? Recommendation: We suggest not applying mupirocin/gentamicin ointment to the exit sites of PD patients (GRADE 2C). CQ4: Which surgical approach is more desirable when a PD catheter is placed, open surgery or laparoscopic surgery? No recommendation. CQ5: Which administration route of antibiotics is better in PD patients with peritonitis, intravenous or intraperitoneal? Recommendation: We suggest intraperitoneal administration of antibiotics in PD patients with peritonitis (GRADE 2C). Note: The National Insurance does not currently cover intraperitoneal administration. CQ6: Is peritoneal dialysis or hemodialysis better as the first renal replacement therapy in diabetic patients? No recommendation. Conclusions In the future, we suggest that society members construct their own evidence to answer CQs not brought up in this guideline, and thereby show the achievements of Japan worldwide.

Abstract Approximately 10 years have passed since the Peritoneal Dialysis Guidelines were formulated in 2009. Much evidence has been reported during the succeeding years, which were not taken into consideration in the previous guidelines, e.g., the next peritoneal dialysis PD trial of encapsulating peritoneal sclerosis (EPS) in Japan, the significance of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), the effects of icodextrin solution, new developments in peritoneal pathology, and a new international recommendation on a proposal for exit-site management. It is essential to incorporate these new developments into the new clinical practice guidelines. Meanwhile, the process of creating such guidelines has changed dramatically worldwide and differs from the process of creating what were “clinical practice guides.” For this revision, we not only conducted systematic reviews using global standard methods but also decided to adopt a two-part structure to create a reference tool, which could be used widely by the society’s members attending a variety of patients. Through a working group consensus, it was decided that Part 1 would present conventional descriptions and Part 2 would pose clinical questions (CQs) in a systematic review format. Thus, Part 1 vastly covers PD that would satisfy the requirements of the members of the Japanese Society for Dialysis Therapy (JSDT). This article is the duplicated publication from the Japanese version of the guidelines and has been reproduced with permission from the JSDT.

Abstract Background The association of glycated albumin (GA) with mortality is unclear in chronic hemodialysis patients with diabetes. We investigated the usefulness of GA by comparing it with hemoglobin A1c (HbA1c) in this patient population. Research design and methods This was a multi-center, prospective cohort study of 841 Japanese chronic hemodialysis patients with diabetes. There were 235 women and 606 men included, with a mean age of 64 years. The primary and secondary endpoints were the incidence of all-cause and cause-specific mortality, respectively. The hazard ratios of GA and HbA1c for the endpoints were estimated using the values at baseline and during the study period. Results During the mean follow-up period of 3.1 years, there were 184 deceased cases, in which 30 and 154 resulted from atherosclerotic cardiovascular disease (ASCVD) and non-ASCVD, respectively. The hazard ratio for a 1% increase in GA was 1.033 (95% confidence interval 1.006–1.060, p = 0.017) for all-cause mortality with a statistical significance when GA was treated as a time dependent variable, but not when the baseline levels or the mean levels during the follow-up period were used in the analysis (p = 0.815 and 0.517, respectively). GA was a significant predictor for ASCVD-related mortality in the above 3 models, but was not for non-ASCVD mortality. Higher levels of HbA1c were only associated with ASCVD-related mortality when HbA1c was treated as a time-dependent variable. Conclusions GA may be useful compared to HbA1c for predicting all-cause and ASCVD-related mortality in Japanese patients with diabetes undergoing chronic hemodialysis.

Abstract Background Renin-angiotensin system inhibitors (RASIs), either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, are widely used in patients with non-dialysis chronic kidney disease, as a renin-angiotensin system (RAS) blockade has renoprotective effects. Several studies show that preserving residual renal function is important for a better prognosis in peritoneal dialysis (PD) patients. Here, we systematically reviewed the beneficial or harmful effects of RAS blockade in PD patients. Methods PubMed, the Cochrane Library, Embase, the Ichushi web databases, and other resources were selected to search clinical guidelines, systematic reviews, and randomized controlled trials (RCT) published before April 14, 2017, using “peritoneal dialysis,” “angiotensin-converting enzyme inhibitors,” “angiotensin II type 1 receptor blockers,” and “randomized controlled trial” as keywords. Desired results were total mortality, technical survival, urine volume, residual renal function calculated by glomerular filtration rate (GFR), cardiovascular events, and anuria progression rate. The study protocol is registered in PROSPERO (International Prospective Register of Systematic Reviews) under the registration number CRD42018104106. Results Of a total of 339 studies, eight were identified as suitable for the analysis. Only one study was blinded, whereas the other seven studies were open-label. RASI appeared to preserve residual renal function, GFR (4 studies, 163 participants, mean difference [MD] 0.97 mL/min/1.73 m2, 95% confidence interval [CI] 0.49–1.44), and urine volume (6 studies, 194 participants, MD 142.56 mL 95% CI 25.42–259.69), although there were no beneficial effects of RASI on total mortality, technical survival, cardiovascular events, and anuria rate. Conclusions Our analysis found that RASIs contribute to preserving GFR and urine volume in PD patients. As the number of study participants is small, further studies with a larger sample size are required.

This data article provides the results of skin sensitization testing for emu and macadamia nut oil on 20 participants (ages 22â59 years old), including 3 men and 17 women. The test was carried out by performing a standard patch test using a Finn Chamber on Scanpor tape. The oils were applied to the participant's back using the tape and left in place for 24Â h. After 1- and 24-h from removal of the tape, the reaction of the participant's skin was judged based on a scoring method recommended by Japanese Patch Test Research Group. Results are shown in table format. Keywords: Emu, Macadamia nut, Safety, Patch test

Here, we present data on the effects of emu oil, obtained from emu (Dromaius novaehollandiae) fat deposits, on melanogenesis in B16F1 murine melanoma cells. The cells were cultured in media containing different concentrations of emu oil, and the melanin content of these cells was measured using a microplate reader. Next, melanin content was measured for cells cultured with α-melanocyte-stimulating hormone. This article reports the different melanin contents as μg melanin/mg cellular protein, by using bar graphs with error bars. The present data imply that emu oil reduces the cellular melanin production.

Serotype C and D of Clostridium botulinum produce botulinum toxin complex (TC), which is comprised of botulinum neurotoxin, nontoxic nonhemagglutinin, and hemagglutinins (HAs). The TC is capable of aggregating equine erythrocytes via interaction between one of the HAs, namely HA-33, and sugar chains on the cell surface. This hemagglutination is inhibited by specific sugars. In this data article, we used four TCs from serotype C and D strains. The hemagglutination-inhibiting effects of 18 sugars and 8 glycoproteins were studied. The purified TC was mixed with the sugar to enable binding of the sugar to the TC; then, the erythrocytes were added to the mixture. Specific binding between the sugar and TC resulted in inhibition of cell aggregation. Here, data illustrating the inhibitory effects of various sugars and glycoproteins against hemagglutination induced by TC of C. botulinum serotypes C and D are presented.