Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3).

INTRODUCTION: ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not. RESEARCH DESIGN AND METHODS: Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year. RESULTS: The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR. CONCLUSIONS: Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD. TRIAL REGISTRATION NUMBER: UMIN000011525.

Generation of sub-5 nm AuNPs in the special space of the loop-cluster corona of a polymer vesicle: preparation and its unique catalytic performance in the reduction of 4-nitrophenol.

The hybrid vesicle AuNP@LCCV, in which a large number of AuNPs with an average size of about 2.8 nm were densely and uniformly distributed in an isolated state throughout the corona of the unusual polymer vesicle, was prepared via in situ reduction of Au3+ ions, which were encapsulated in advance in the unique polymer vesicle (LCCV) consisting of a hydrophobic membrane of poly(2-phenyl-2-oxazoline) and a hydrophilic loop-cluster corona of polyethyleneimine. The vesicle was formed via self-assembly from a comb-like block copolymer in which a polystyrenic main chain was grafted densely with diblock polyethyleneimine-b-poly(2-phenyl-2-oxazoline) and acted as a reactor for the reduction of Au3+. The hybrid vesicle AuNP@LCCV showed powerful catalytic ability in the reduction of nitrophenols (NPs). Interestingly, the reduction reactions of NPs showed a remarkably long induction time, which could be shortened dramatically from 60 min to 1-2 min by greatly increasing the concentration of NaBH4. It is revealed that the oxygen adsorbed on the AuNPs significantly inhibited the reduction, causing the induction time. Once the oxygen is chemically cleaned from the surface of the AuNPs, the reduction of 4-NP proceeds gradually for a while and then completes suddenly. The reduction mechanism accompanying the oxygen-dependent induction time is proposed from the view of the strong oxygen affinity of the catalyst AuNP@LCCV.

Diastereoselective Synthesis of trans-anti-Hydrophenanthrenes via Ti-mediated Radical Cyclization and Total Synthesis of Kamebanin.

Ent-kaurenes consist of an ABC-ring based on a trans-anti-hydrophenanthrene skeleton and a D ring with an exomethylene. Highly oxygen-functionalized ent-kauren-15-ones have promising antiinflammatory pharmacological activity. In this study, we developed a novel diastereoselective synthesis of trans-anti-hydrophenanthrenes via a Ti-mediated reductive radical cyclization. We also demonstrated the applicability of this method by developing the first total synthesis of (±)-kamebanin (longest linear sequence; 17 steps, overall yield; 6.5 %). Furthermore, this synthesis provided a formal semi-pinacol rearrangement for the construction of the quaternary carbon at C8 and a novel Thorpe-Ziegler-type reaction for the construction of the D-ring.

Octreotide LAR was useful for avoiding hypoglycemia in an elderly patient with insulinoma.

An 80-year-old woman was admitted to our hospital with a hypoglycemia attack. She was diagnosed with insulinoma based on her high insulin level at the time of the hypoglycemia attack and the presence of a hypervascular tumor in her pancreas. The patient refused surgical treatment and octreotide was used to prevent hypoglycemia.It is known that octreotide suppresses the secretion of insulin from the pancreas; however, insulin secretion is not always suppressed in patients with insulinoma. Moreover, there is no particular protocol for the use of octreotide in the treatment of insulinoma.We examined the effect of octreotide in preventing hypoglycemia using CGM. The injection of octreotide (50 µg) at 21: 00 prevented hypoglycemia during the night.However the patient could not perform self-injection due to the sequelae of a cerebral infarction. We therefore chose to have her eat an extra meal at 11 pm.After a while the patient became exhausted by eating meals at night. We examined the effects of octreotide LAR using CGM, and it was found to prevent hypoglycemia for 4 weeks. The patient's QOL was improved by being released from a restriction that affected her daily life.

Enantioseparation of 1-arylethanols via a supramolecular chiral host consisting of N-(2-naphthoyl)-L-aspartic acid and an achiral diamine.

A supramolecular chiral host consisting of N-(2-naphthoyl)-L-aspartic acid (L-1) and meso-1,2-diphenylethylenediamine (2) is effective in enantioseparation of 1-arylethanols (up to 96% ee with 100% inclusion ratio). Here we report three different methods to prepare the inclusion crystals and discuss the chiral recognition mechanism on the basis of X-ray crystallography results.