A multi-center randomized controlled trial to investigate potential effects of exercise therapy on renal function stratified by renal disorders and renal pathology: beneficial or harmful effect in immunoglobulin a nephropathy.

BACKGROUND: The effects of exercise therapy (ET) on renal function in chronic kidney disease (CKD) remain unclear. METHODS: In a randomized controlled trial (UMIN-CTR number: UMIN000038415), we investigated whether ET affects renal function in CKD; eligible patients had undergone renal biopsy in the past 3 months. We stratified patients by disease (immunoglobulin A [IgA] nephropathy, n = 16; diabetic nephropathy, n = 4; benign nephrosclerosis, n = 13; and other CKD types, n = 13) and randomized them to 12 weeks' observation and 24 weeks' ET comprising home-based aerobic exercise 3×/week and resistance training 2×/week (intervention group) or usual care (non-intervention group). Primary endpoint was creatinine-based estimated glomerular filtration rate (eGFR) or serum cystatin C-based eGFR (eGFRcys). Secondary endpoints included urinary protein and exercise tolerance. RESULTS: Seventy patients were enrolled, 50 fulfilled the inclusion criteria, but 4 discontinued before randomization. No items significantly differed between week 0 to 24 in either group (intervention group, n = 23; non-intervention group, n = 23) or between groups at week 24 (intention-to-treat population) in the total study population. The eGFRcys slope showed no significant intergroup difference in the observation period, but eGFRcys improved significantly in IgA nephropathy patients (n = 16) in the intervention group (stratified comparison; week 0, 48.3 ± 18.2; week 24, 51.6 ± 17.6; p = 0.043). In these patients, urinary protein was significantly worse at week 24 in the non-intervention group (p = 0.046) and worsened significantly less in the intervention group (p = 0.039). CONCLUSION: ET did not improve renal function overall in CKD patients but might help maintain renal function in patients with IgA nephropathy.

Hyperchloremic acidosis develops at the stage G4 and shifts to high anion gap acidosis at the stage G5 in chronic kidney disease.

BACKGROUND: Amelioration of hyperchloremic acidosis (Cl-Ac), a common complication in chronic kidney disease (CKD), could preserve renal function in chronic kidney disease (CKD). However, the development of Cl-Ac in CKD has not been clarified yet. METHODS: The degree of Cl-Ac, which is indicated as the bicarbonate concentration decrease with serum chloride concentration increase (∆[HCO3-]Cl), was compared with the estimated glomerular filtration rate (eGFR) by using CKD patient records. RESULTS: In 307 records with metabolic acidosis, a spline curve obtained from the plot comparing ∆[HCO3-]Cl with eGFR showed that ∆[HCO3-]Cl did not change, increased, and decreased during eGFR decrease until 27, from 27 to 17.5, and from 17.5 mL/min/1.73 m2, respectively. CONCLUSION: By CKD progression, Cl-Ac progressed and regressed at the CKD stages G4 and G5, respectively. The regression would have reflected the shift of Cl-Ac to high anion gap acidosis.

Synthesis, Characterization, and Magnetic Resonance Evaluation of Polyglycerol-Functionalized Detonation Nanodiamond Conjugated with Gadolinium(III) Complex.

A nanodiamond-polyglycerol-gadolinium(ll) conjugate has been designed and prepared as novel nanodiamond-based magnetic resonance (MR) contrast agent dispersible in physiological media. Detonation nanodiamond (dND) was first grafted with polyglycerol (PG) through ring-opening polymerization of glycidol to impart dispersibility to dND in physiological media. Since the hydroxyl group in PG serves as a scaffold for further surface functionalization, diethylenetriaminepentaacetic acid (DTPA) was immobilized on the surface of dND-PG through multistep organic transformations and Gd(III) ion was complexed in the last step. The resulting dND-PG-Gd(III) exhibited good dispersibility (> 4.5 mg/mL) and stability (> 3 months) in phosphate buffered saline (PBS). In vitro MR evaluation indicates that water proton T1 relaxivity or r1 of dND-PG-Gd(III) in aqueous solutions is larger than that of Magnevist® and the difference in the relaxivity becomes larger under weaker magnetic fields. The good dispersibility together with relatively high T1 relaxivity makes dND-PG-Gd(III) a promising contrast agent for in vivo MR imaging.

Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA.

A gene vector consisting of nanodiamond, polyglycerol, and basic polypeptide (ND-PG-BPP) has been designed, synthesized, and characterized. The ND-PG-BPP was synthesized by PG functionalization of ND through ring-opening polymerization of glycidol on the ND surface, multistep organic transformations (-OH → -OTs (tosylate) → -N3) in the PG layer, and click conjugation of the basic polypeptides (Arg8, Lys8 or His8) terminated with propargyl glycine. The ND-PG-BPP exhibited good dispersibility in water (>1.0 mg/mL) and positive zeta potential ranging from +14.2 mV to +44.1 mV at neutral pH in Milli-Q water. It was confirmed by gel retardation assay that ND-PG-Arg8 and ND-PG-Lys8 with higher zeta potential hybridized with plasmid DNA (pDNA) through electrostatic attraction, making them promising as nonviral vectors for gene delivery.

Simultaneous discrimination of diameter, handedness, and metallicity of single-walled carbon nanotubes with chiral diporphyrin nanocalipers.

We have been developing the methodology to discriminate the handedness and diameter of single-walled carbon nanotubes (SWNTs) through molecular recognition using chiral diporphyrin nanotweezers. Although relatively small diameters of SWNTs (<1.0 nm) were recognized well, nanotweezers were not able to form stable complexes with the SWNTs having the diameters >1.0 nm. In this context, we designed chiral diporphyrin with a much larger cavity, namely, "nanocalipers". The feature of the newly designed host molecule is: (1) long spacer with more than 1.4 nm consisting of three aromatic moieties; (2) nearly parallel orientation of the two porphyrins; (3) restricted conformation by biaryl linkages of the porphyrin-carbazole and carbazole-anthracene; (4) strong interaction of two porphyrins and anthracene with the surface of a SWNT through π-π stacking; and (5) stereogenic centers at the periphery of porphyrins discriminating helicity of SWNTs. As expected, we obtained optically active SWNTs with >1.0 nm in diameter and, unexpectedly, enriched metallic SWNTs over semiconducting ones. The optically active metallic SWNTs are identified for the first time, in addition to the optically active semiconducting SWNTs with such large diameters. The nanocalipers are found to recognize the diameter, handedness, and metallicity of SWNTs simultaneously.

Bis(tert-butylpyrene) nanotweezers and nanocalipers: enhanced extraction and recognition abilities for single-walled carbon nanotubes.

We developed a host-guest methodology for separation of single-walled carbon nanotubes (SWNTs) according to the handedness, diameter and metallicity by the use of diporphyrin nanotweezers and nanocalipers. Although the pyrene has been frequently used to replace porphyrin, due to a similar affinity to the surface of SWNTs and better availability, the extraction and recognition abilities of dipyrene nanotweezers were not so good as those of diporphyrin ones as we reported previously. However, introduction of a tert-butyl substituent at the 7'-position of 2-pyrene is found to enhance the extraction and recognition abilities of dipyrene nanotweezers and nanocalipers. That is, (6,5)-SWNTs were obtained in high purity by use of bis(tert-butylpyrene) nanotweezers with a phenanthrene spacer and metallic SWNTs were highly enriched by use of bis(tert-butylpyrene) nanocalipers with a carbazole-anthracene-carbazole spacer.

A multi-institutional, observational study of outcomes after catheter placement for peritoneal dialysis in Japan.

BACKGROUND: This multi-institutional, observational study examined whether the outcomes after peritoneal dialysis (PD) catheter placement in Japan meet the audit criteria of the International Society for Peritoneal Dialysis (ISPD) guideline and identified factors affecting technique survival and perioperative complications. METHODS: Adult patients who underwent first PD catheter placement for end-stage kidney disease between April 2019 and March 2021 were followed until PD withdrawal, kidney transplantation, transfer to other facilities, death, 1 year after PD start or March 2022, whichever came first. Primary outcomes were time to catheter patency failure and technique failure, and perioperative infectious complications within 30 days of catheter placement. Secondary outcomes were perioperative complications. Appropriate statistical analyses were performed to identify factors associated with the outcomes of interest. RESULTS: Of the total 409 patients, 8 who underwent the embedded catheter technique did not have externalised catheters. Of the 401 remaining patients, catheter patency failure occurred in 25 (6.2%). Technical failure at 12 months after PD catheter placement calculated from cumulative incidence function was 15.3%. On Cox proportional hazards model analysis, serum albumin (hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27-0.70) and straight type catheter (HR 2.14; 95% CI 1.24-3.69) were the independent risk factors for technique failure. On logistic regression analysis, diabetes mellitus was the only independent risk factor for perioperative infectious complications (odds ratio 2.70, 95% CI 1.30-5.58). The occurrence rate of perioperative complications generally met the audit criteria of the ISPD guidelines. CONCLUSION: PD catheter placement in Japan was proven to be safe and appropriate.

Preferential extraction of left- or right-handed single-walled carbon nanotubes by use of chiral diporphyrin nanotweezers.

Handedness- and diameter-based separation of single-walled carbon nanotubes was achieved through preferential extraction of 76-CoMoCAT with 2,6-pyridylene-bridged chiral diporphyrin nanotweezers.

Simultaneous discrimination of handedness and diameter of single-walled carbon nanotubes (SWNTs) with chiral diporphyrin nanotweezers leading to enrichment of a single enantiomer of (6,5)-SWNTs.

Separation of single-walled carbon nanotubes (SWNTs) according to their handedness has been attracting growing interest. Our methodology to separate the enantiomers of SWNTs is based on molecular recognition with chiral diporphyrin nanotweezers. Herein, we report novel nanotweezers 1 consisting of two chiral porphyrins and phenanthrene in between. These nanotweezers 1 are rationally designed to discriminate diameter and handedness simultaneously by taking into account the relationship between the (n, m) selectivity and the structures of previously reported chiral nanotweezers. Owing to the relatively narrow cleft made by two porphyrins, the nanotweezers 1 showed high selectivity toward (6,5)-SWNTs possessing the smallest diameter among the major components of CoMoCAT-SWNTs. In addition, the chiral diporphyrin 1 discriminated the left- and right-handed structures of (6,5)-SWNTs, providing high enantiomeric excess (67% ee on the basis of the (6,5)-SWNTs with high optical purity recently reported by Weisman). In conclusion, only the single stereoisomer of (6,5)-SWNTs was highly enriched through the extraction of CoMoCAT-SWNTs with phenanthrene-bridged chiral diporphyrin nanotweezers 1.

Salvation of peritoneal dialysis catheter potency by using an angiographic guidewire.

Catheter obstruction is a major cause of dialysate flow problems in peritoneal dialysis (PD). It will lead to PD technique failure, when its conservative management such as vigorous instillation of dialysate occasionally fails to salvage the catheter potency. In this report, we present two cases of catheter obstruction caused by intraluminal clots of PD catheter. The clots, which could not be removed by the conservative management, were removed by a new technique using an angiographic guidewire. The technique could be an option to resolve PD catheter obstruction.

Misdiagnosis of high anion gap acidosis owing to instrument error of a device.

The anion gap (AG) is a tool to diagnose metabolic acid-base disorders in the physiological approach to acid-base assessment. It is used to detect high AG acidosis, a type of metabolic acidosis caused by serum concentration increase in usually unmeasured anions; AG larger than the reference for it indicates the presence of high AG acidosis. This report presents a case of hyperlactatemia which was not detected as high AG acidosis possibly because of instrument error of a device in measurement of serum sodium and chloride concentrations. The case indicates that the error will make AG unable to detect high AG acidosis of any cause. Hence, upon suspicion of high AG acidosis caused by measurable anions such as lactate and ketones, it is recommended to measure their serum concentration.

Unexpectedly large binding constants of azulenes with fullerenes.

In spite of having small pi-conjugation systems, azulenes show large binding constants (10(4)-10(5)) to C(60) and C(70), which are larger than those of monoporphyrins and alternant aromatic hydrocarbons.

Photophysical properties of a novel Ni(II)-diporphyrin in presence of fullerenes: insights from experimental and theoretical studies.

The present paper highlights the photophysical aspects of the topologically new Ni(II)-diporphyrin (Ni(2)-1)/fullerene host-guest ensembles. Both absorption and fluorescence studies reveal that Ni(2)-1 undergoes efficient complexation with both C(60) and C(70) in toluene medium. In the fluorescence study, remarkable enhancement of the fluorescence intensity of Ni(2)-1 was observed by the addition of C(60), while normal quenching of fluorescence occurred in case of C(70). From the fluorescence and UV-vis studies, the binding constants of Ni(2)-1 with C(60) and C(70) were determined to be approximately 1.7 x 10(4) and approximately 2.7 x 10(4) dm(3) mol(-1), respectively. Ab initio theoretical calculations reveal that C(70)/Ni(2)-1 complex favor end-on orientation of C(70) rather than side-on approach.

Improved optical enrichment of SWNTs through extraction with chiral nanotweezers of 2,6-pyridylene-bridged diporphyrins.

Chiral single-walled carbon nanotubes (SWNTs) have left- and right-handed helical structures (M and P, respectively, according to the IUPAC nomenclature). In this report, optically active SWNTs were obtained through preferential extraction of (M)- or (P)-SWNTs with 2,6-pyridylene-bridged chiral diporphyrins 1. In the circular dichroism (CD) spectra, the SWNTs extracted with 1 exhibit much larger intensity than those extracted with 1,3-phenylene-bridged chiral diporphyrins 2, indicating an improved chiral discrimination ability of 1. In particular, (6,5)-SWNTs display the most intensified CD signals among the SWNTs extracted with 1. In addition, the SWNT extraction ability of 1 has been shown to be considerably enhanced in comparison to 2. These improved discrimination and extraction abilities of 1 are attributed to the formation of its more stable SWNT complex. Computer-calculated energy minimized structures for 1:(6,5)-SWNT complexes show that (R)- and (S)-1 form complexes preferentially with (M)- and (P)-(6,5)-SWNTs, respectively. These calculations also predict that the 1:(6,5)-SWNT complex is approximately 1.6 kcal mol-1 more stable than the corresponding complex of 2, accounting for the improved abilities of 1 in the chiral discrimination and extraction.

Spectral and theoretical studies on effective and selective non-covalent interaction between tetrahexylporphyrins and fullerenes.

The host-guest interaction of zinc(II) 5,10,15,20-tetrahexylporphyrin (Zn-THP) and its free base (H2-THP) with fullerenes (C60 and C70) has been studied in toluene medium. Binding constants (K) for H2- and Zn-THP complexes of fullerenes were determined by UV-vis, fluorescence and NMR spectroscopic techniques. Large K values of C70/THP complexes (KC70 ) were obtained in the range of 1.4-2.5 x 10(4)M(-1), while those of C60/THP complexes (KC60) were smaller (1.0-3.2 x10(3)M(-1)). These results show that the KC70 is about 10 times as large as KC60 in both THPs (KC70/KC60 = 10). Enthalpies of formation (DeltaHf degrees) for various fullerene/THP complexes were estimated by ab initio calculations; DeltaHf degrees for C60/H2-THP, C70/H2-THP, C60/Zn-THP and C70/Zn-THP complexes are 5.82, 2.80, 2.31 and 1.54 kcal mol(-1), respectively. The trends in DeltaHf degrees support the experimental results of selective complexation of THPs towards C70 over C60 and fullerenes towards Zn-THP over H2-THP.