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1.
Dev Sci ; : e13388, 2023 Mar 17.
Article in English | MEDLINE | ID: mdl-36929667

ABSTRACT

This study compared parenting across four non-Western cultures to test cross-cultural commonality and specificity principles in three aspects: measurement properties, parenting normativeness, and their associations with child outcomes. Both mothers and fathers (N = 1509 dyads) with preschool-aged children (M = 5.00 years; 48% girls) from urban areas of four countries (Malaysia, N = 372; China, N = 441; Turkey, N = 402; and Japan, N = 294) reported on four parenting constructs (authoritative, authoritarian, group harmony socialization, and intrusive control) and their sub-dimensions using modified culturally relevant measures. Teachers reported on children's internalizing, externalizing, and prosocial behaviors. The commonality principle was supported by two sets of findings: (1) full measurement invariance was established for most parenting constructs and sub-dimensions, except that intrusive control only reached partial scalar invariance, and (2) no variations were found in associations between parenting and any child outcomes across cultures or parent gender at the construct level for all four parenting constructs and at the sub-dimensional level for authoritarian and intrusive control sub-dimensions. The specificity principle was supported by the other two sets of findings: (1) cross-cultural differences in parenting normativeness did not follow the pattern of economic development but yielded culture-specific patterns, and (2) at the sub-dimensional level, the authoritative parenting and group harmony socialization sub-dimensions were differently associated with child outcomes across cultures and/or parent gender. The findings suggested that examining specific dimensions rather than broad parenting constructs is necessary to reflect cultural specificities and nuances. Our study provided a culturally-invariant instrument and a three-step guide for future parenting research to examine cross-cultural commonalities/specificities. RESEARCH HIGHLIGHTS: This is the first study to use an instrument with measurement invariance across multiple non-Western cultures to examine the commonality and specificity principles in parenting. Measurement invariance was achieved across cultures for authoritative and authoritarian parenting, group harmony socialization, intrusive control, and their sub-dimensions, supporting the commonality principle. Cross-cultural differences in parenting normativeness did not follow the pattern of economic development but yielded culture-specific patterns, supporting the specificity principle. Both commonalities and specificities were manifested in associations between parenting and child outcomes across cultures.

2.
Molecules ; 27(19)2022 Sep 28.
Article in English | MEDLINE | ID: mdl-36234952

ABSTRACT

Conversion from superoxide (O2-) to hydroperoxide (OOH-) on the metal center of oxygenases and oxidases is recognized to be a key step to generating an active species for substrate oxidation. In this study, reactivity of cobalt(III)-superoxido complexes supported by facially-capping tridentate tris(3,5-dimethyl-4-X-pyrazolyl)hydroborate ([HB(pzMe2,X)3]-; TpMe2,X) and bidentate bis(1-methyl-imidazolyl)methylborate ([B(ImN-Me)2Me(Y)]-; LY) ligands toward H-atom donating reagent (2-hydroxy-2-azaadamantane; AZADOL) has been explored. The oxygenation of the cobalt(II) precursors give the corresponding cobalt(III)-superoxido complexes, and the following reaction with AZADOL yield the hydroperoxido species as has been characterized by spectroscopy (UV-vis, resonance Raman, EPR). The reaction of the cobalt(III)-superoxido species and a reducing reagent ([CoII(C5H5)2]; cobaltocene) with proton (trifluoroacetic acid; TFA) also yields the corresponding cobalt(III)-hydroperoxido species. Kinetic analyses of the formation rates of the cobalt(III)-hydroperoxido complexes reveal that second-order rate constants depend on the structural and electronic properties of the cobalt-supporting chelating ligands. An electron-withdrawing ligand opposite to the superoxide accelerates the hydrogen atom transfer (HAT) reaction from AZADOL due to an increase in the electrophilicity of the superoxide ligand. Shielding the cobalt center by the alkyl group on the boron center of bis(imidazolyl)borate ligands hinders the approaching of AZADOL to the superoxide, although the steric effect is insignificant.


Subject(s)
Cobalt , Superoxides , Azoles , Borates , Boron , Cobalt/chemistry , Crystallography, X-Ray , Electronics , Hydrogen Peroxide , Ligands , Oxidoreductases , Oxygenases , Protons , Trifluoroacetic Acid
3.
Psychol Rep ; : 332941221133010, 2022 Oct 15.
Article in English | MEDLINE | ID: mdl-36250541

ABSTRACT

This longitudinal study investigated the roles of elementary schoolers' executive function (EF) and theory of mind (ToM) as predictors in their academic achievements in Japanese language skills (e.g., speaking and listening ability, writing ability, reading ability, and linguistic knowledge) from first through fifth grade. We assessed the EF, ToM, and academic achievements of 85 Japanese elementary schoolers, when they were grade 1 (M = 90.19 months) and grade 3 (M = 114.34 months). Moreover, academic achievements of same children tested in grade 5 (M = 137.92 months). A path analysis revealed that EF abilities in Grades 1 and 3 predicted Japanese language achievement via ToM ability, and EF and ToM in Grade 1 had an indirect effect on achievements in Grades 3 and 5. Further, Japanese language skills achievement in Grade 1 predicted EF ability in Grade 3 and EF predicted achievement in Grade 5. These findings indicate the vital role of elementary schoolers' EF on academic achievement in Japan.

4.
Intern Med ; 61(12): 1823-1833, 2022.
Article in English | MEDLINE | ID: mdl-35705311

ABSTRACT

Objective Evaluating the rate of decline in the estimated glomerular filtration rate (eGFR) may help identify patients with occult chronic kidney disease (CKD). We herein report that eGFR fluctuation complicates the assessment of the rate of decline and propose a long-term eGFR plot analysis as a solution. Methods In 142 patients with persistent eGFR decline in a single hospital, we evaluated the factors influencing the rate of eGFR decline, calculated over the long term (≥3 years) and short term (<3 years) using eGFR plots, taking into account eGFR fluctuation between visits. Results The difference between the rate of eGFR decline calculated using short- and long-term plots increased as the time period considered in the short-term plots became shorter. A regression analysis revealed that eGFR fluctuation was the only factor that explained the difference and that the fluctuation exceeded the annual eGFR decline in all participants. Furthermore, the larger the eGFR fluctuation, the more difficult it became to detect eGFR decline using a short-term eGFR analysis. Obesity, a high eGFR at baseline, and faster eGFR decline were associated with larger eGFR fluctuations. To circumvent the issue of eGFR fluctuation in the assessment of the rate of eGFR decline, we developed a system that generates a long-term eGFR plot using all eGFR values for a participant, which enabled the detection of occult CKD, facilitating early therapeutic intervention. Conclusion The construction of long-term eGFR plots is useful for identifying patients with progressive eGFR decline, as it minimizes the effect of eGFR fluctuation.


Subject(s)
Renal Insufficiency, Chronic , Glomerular Filtration Rate , Humans , Kidney/physiology , Obesity , Regression Analysis , Risk Factors
5.
Dalton Trans ; 51(27): 10338-10342, 2022 Jul 12.
Article in English | MEDLINE | ID: mdl-35703587

ABSTRACT

A novel anionic tridentate borate ligand with a 6-methylpyridyl donor, TpyMe, has been synthesized. Comparison of the molecular structures and reactivities of nickel(II)-bromido complexes with tris(azolyl)borate ligands composed of pyridyl, pyrazolyl, or oxazolinyl donors indicates the characteristic sterically demanding nature and strong electron donating ability of TpyMe.

6.
Dalton Trans ; 49(18): 6108-6118, 2020 May 14.
Article in English | MEDLINE | ID: mdl-32323686

ABSTRACT

Tris(oxazolynylmethyl)amine TOAR (where R denotes the substituent groups on the fourth position of the oxazoline rings) complexes of nickel(ii) have been synthesized as catalyst precursors for alkane oxidation with meta-chloroperoxybenzoic acid (m-CPBA). The molecular structures of acetato, nitrato, meta-chlorobenzoato and chlorido complexes with TOAMe2 have been determined using X-ray crystallography. The bulkiness of the substituent groups R affects the coordination environment of the nickel(ii) centers, as has been demonstrated by comparison of the molecular structures of chlorido complexes with TOAMe2 and TOAtBu. The nickel(ii)-acetato complex with TOAMe2 is an efficient catalyst precursor compared with the tris(pyridylmethyl)amine (TPA) analogue. Oxazolynyl donors' strong σ-electron donating ability will enhance the catalytic activity. Catalytic reaction rates and substrate oxidizing position selectivity are controlled by the structural properties of the R of TOAR. Reaction of the acetato complex with TOAMe2 and m-CPBA yields the corresponding acylperoxido species, which can be detected using spectroscopy. Kinetic studies of the decay process of the acylperoxido species suggest that the acylperoxido species is a precursor of an active species for alkane oxidation.

7.
Dalton Trans ; 48(8): 2564-2568, 2019 Feb 19.
Article in English | MEDLINE | ID: mdl-30720815

ABSTRACT

Exposure of O2 to a reaction mixture containing bis(acac)cobalt(ii), a facially capping tris(N-heterocyclic carbene)borate ligand and 1-methylimidazole yields a heteroleptic cobalt(iii) complex with acac, 1-methylimidazole and tris(NHC)borate ligands. meta-Chloroperbenzoic acid is efficiently activated by this heteroleptic complex to catalytically oxidize cyclohexane at ambient temperature.

8.
Inorg Chem ; 57(22): 14218-14229, 2018 Nov 19.
Article in English | MEDLINE | ID: mdl-30376312

ABSTRACT

The effects of the substituents on the chelating ligands located in the secondary coordination sphere on the O2 affinity of cobalt(II) centers have been explored. The combination of facially capping tridentate tris(pyrazolyl)borates (= TpMe2,4R) and bidentate bis(imidazolyl)borates (= [B(Im N-Me)2MeX]- ; LX) yields square-pyramidal cobalt(II) complexes. The structural properties of the substituent groups X attached to the boron center of LX affect the arrangement of X in the resulting cobalt(II) complexes [CoII(TpMe2,4R)(LX)]. When the boron-attached moiety of X is a relatively bulky sp3-CH2Y group (i.e., X:Y = Me:H and nBu: nPr), the alkyl group X faces the cobalt center, whereas for isopropoxy (O iPr) and phenyl (Ph) groups, of which the boron-attached atoms are a less hindered oxygen atom and a planer sp2-carbon, respectively, the X group is arranged away from the cobalt center. This flexible behavior of LX is reflected in the O2 affinity of the cobalt(II) center, which depends on the extent to which the complex sphere is shielded by the ligands. The dependence of the cobalt(II) oxidation potential on the X substituent of LX is inconsistent with the O2 affinity. On the other hand, the electronic properties of R, which is attached to the fourth position of the pyrazolyl rings in the rigid TpMe2,4R ligand, are reflected in the electrochemical properties and O2 affinity of the cobalt center.

9.
Molecules ; 23(6)2018 Jun 16.
Article in English | MEDLINE | ID: mdl-29914171

ABSTRACT

Scorpionate ligands Tp* (hydrotris(3,5-dimethylpyrazol-1-yl)borate) and ToM (tris(4,4-dimethyloxazolin-2-yl)phenylborate) complexes of cobalt(II) with bidentate ligands were synthesized. Both Tp* and ToM coordinate to cobalt(II) in a tridentate fashion when the bidentate ligand is the less hindered acetylacetonate. In crystal structures, the geometry of cobalt(II) supported by the N3O2 donor set in the Tp* complex is a square-pyramid, whereas that in the ToM complex is close to a trigonal-bipyramid. Both Tp*- and ToM-acac complexes exhibit solvatochromic behavior, although the changing structural equilibria of these complexes in MeCN are quite different. In the bis(1-methylimidazol-2-yl)methylphenylborate (LPh) complexes, Tp* retains the tridentate (к³) mode, whereas ToM functions as the bidentate (к²) ligand, giving the tetrahedral cobalt(II) complex. The bowl-shaped cavity derived from the six methyl groups on ToM lead to susceptibility to the bulkiness of the opposite bidentate ligand. The entitled scorpionate compounds mediate hydrocarbon oxidation with organic peroxides. Allylic oxidation of cyclohexene occurs mainly on the reaction with tert-butyl hydroperoxide (TBHP), although the catalytic efficiency of the scorpionate ligand complexes is lower than that of Co(OAc)2 and Co(acac)2. On cyclohexane oxidation with meta-chloroperbenzoic acid (mCPBA), both ToM and Tp* complexes function as catalysts for hydroxylation. The higher electron-donating ToM complexes show faster initial reaction rates compared to the corresponding Tp* complexes.


Subject(s)
Borates/chemistry , Cobalt/chemistry , Organometallic Compounds/chemistry , Catalysis , Ligands , Molecular Structure
10.
ACS Omega ; 2(3): 1025-1030, 2017 Mar 31.
Article in English | MEDLINE | ID: mdl-31457483

ABSTRACT

To develop novel immobilized metallocomplex catalysts, allyltris(3-trifluoromethylpyrazol-1-yl)borate (allyl-TpCF3) was synthesized. A boron-attached allyl group reacts with thiol to afford the desired mesoporous silica-immobilized TpCF3. Cobalt(II) is an efficient probe for estimating the structures of the immobilized metallocomplexes. The structures of the formed cobalt(II) complexes and their catalytic activity depended on the density of the organic thiol groups and on the state of the remaining sulfur donors on the supports.

11.
Acta Crystallogr C Struct Chem ; 72(Pt 11): 842-845, 2016 Nov 01.
Article in English | MEDLINE | ID: mdl-27811422

ABSTRACT

Poly(pyrazol-1-yl)borates have been utilized extensively in coordination compounds due to their high affinity toward cationic metal ions on the basis of electrostatic interactions derived from the mononegatively charged boron centre. The original poly(pyrazol-1-yl)borates, christened `scorpionates', were pioneered by the late Professor Swiatoslaw Trofimenko and have expanded to include various borate ligands with N-, P-, O-, S-, Se- and C-donors. Scorpionate ligands with boron-carbon bonds, rather than the normal boron-nitrogen bonds, have been developed and in these new types of scorpionate ligands, amines and azoles, such as pyridines, imidazoles and oxazolines, have been employed as N-donors instead of pyrazoles. Furthermore, a variety of bis- and tris(oxazolinyl)borate ligands, including chiral ones, have been developed. Tris(oxazolin-2-yl)borates work as facially capping tridentate chelating ligands in the same way as tris(pyrazol-1-yl)borates. In the title compound, [Ni(C21H29BN3O3)Cl], the NiII ion is coordinated by three N atoms from the facially capping tridentate chelating tris(4,4-dimethyloxazolin-2-yl)phenylborate ligand and a chloride ligand in a highly distorted tetrahedral geometry. The Ni-Cl bond length [2.1851 (5) Å] is comparable to those found in a previously reported tris(3,5-dimethylpyrazol-1-yl)hydroborate derivative [2.1955 (18) and 2.150 (2) Å]. The molecular structure deviates from C3v symmetry due to the structural flexibility of the tris(4,4-dimethyloxazolin-2-yl)phenylborate ligand.

12.
Kidney Int ; 90(6): 1211-1225, 2016 12.
Article in English | MEDLINE | ID: mdl-27591086

ABSTRACT

Hypoxia causes proximal tubular cell damage in diabetes, even though proximal tubular cells have an adaptive system to combat hypoxia involving induction of hypoxia factor-1 (HIF-1) and inhibition of mechanistic target of rapamycin complex 1 (mTORC1). Here, we examined the interference effect of altered glucose and lipid metabolism on the hypoxia responses in proximal tubular cells. In culture, hypoxia alone induced HIF-1 and inhibited mTORC1, preventing death in proximal tubular cells. However, hypoxia with high glucose and palmitate increased mTORC1 activity and promoted apoptosis in proximal tubular cells, which was inhibited by pharmacological and genetic inactivation of mTORC1. Since inhibition of all mTORC1's physiological functions regulated by growth factors including insulin causes various adverse effects, we screened for a microRNA that can inhibit only pro-apoptotic effects of mTORC1 to discover a safe therapeutic target. This screen found microRNA-148b-3p was able to specifically inhibit mTORC1-dependent apoptosis in hypoxic proximal tubular cells exposed to high glucose and palmitate, without affecting insulin-dependent mTORC1 activation. Furthermore, tumor necrosis factor receptor (TNFR) 2 was the target of microRNA-148b-3p and its suppression inhibited apoptosis. Finally, enhanced apoptosis with TNFR2 overexpression was found in hypoxic and mTORC1-activated proximal tubular cells in diabetic rats. Thus, diabetes activated mTORC1 even in hypoxic proximal tubular cells, leading to apoptosis by reducing microRNA-148b-3p expression. Modulating this pathogenic pathway may be a novel therapy for proximal tubular cell damage in diabetes.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Kidney Tubules, Proximal/metabolism , MicroRNAs/metabolism , Multiprotein Complexes/metabolism , Receptors, Tumor Necrosis Factor, Type II/metabolism , TOR Serine-Threonine Kinases/metabolism , Animals , Apoptosis , Cells, Cultured , Glucose , Hypoxia/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Lipid Metabolism , Mechanistic Target of Rapamycin Complex 1 , Mice , Palmitic Acid , Rats , Signal Transduction
13.
Sci Rep ; 6: 18944, 2016 Jan 06.
Article in English | MEDLINE | ID: mdl-26732653

ABSTRACT

Autophagy is an intracellular degradation system activated, across species, by starvation. Although accumulating evidence has shown that mammalian autophagy is involved in pathogenesis of several modern diseases, its physiological role to combat starvation has not been fully clarified. In this study, we analysed starvation-induced gluconeogenesis and ketogenesis in mouse strains lacking autophagy in liver, skeletal muscle or kidney. Autophagy-deficiency in any tissue had no effect on gluconeogenesis during starvation. Though skeletal muscle- and kidney-specific autophagy-deficiency did not alter starvation-induced increases in blood ketone levels, liver-specific autophagy-deficiency significantly attenuated this effect. Interestingly, renal as well as hepatic expression of HMG-CoA synthase 2 increased with prolonged starvation. Furthermore, during starvation, mice lacking autophagy both in liver and kidney showed even lower blood ketone levels and physical activity than mice lacking autophagy only in liver. Starvation induced massive lipid droplet formation in extra-adipose tissues including liver and kidney, which was essential for ketogenesis. Moreover, this process was impaired in the autophagy-deficient liver and kidney. These findings demonstrate that hepatic and renal autophagy are essential for starvation-induced lipid droplet formation and subsequent ketogenesis and, ultimately, for maintaining systemic energy homeostasis. Our findings provide novel biological insights into adaptive mechanisms to combat starvation in mammals.


Subject(s)
Autophagy , Ketone Bodies/biosynthesis , Kidney/metabolism , Liver/metabolism , Starvation/metabolism , Amino Acids/metabolism , Animals , Autophagy-Related Protein 5/deficiency , Autophagy-Related Protein 5/genetics , Blood Glucose , Gluconeogenesis , Ketone Bodies/blood , Lipid Metabolism , Mammals , Mice , Mice, Knockout , Muscle, Skeletal/metabolism
14.
Brain Dev ; 38(4): 377-85, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26542468

ABSTRACT

AIM: To assess the developmental characteristics of very low-birth-weight (VLBW) infants using the Kyoto Scale of Psychological Development (KSPD) and to compare with those using the Bayley Scales, third edition (Bayley III). METHODS: KSPD and Bayley III were performed on 124 Japanese VLBW infants at 18months of corrected age at a 2-week interval by trained psychologists. The relationships between KSPD and Bayley III in corresponding pairs: Cognitive-Adaptive (C-A) developmental quotient (DQ) and cognitive composite (Cog) scores, Language-Social (L-S) DQ and language composite (Lang) scores, and Postural-Motor (P-M) DQ and motor composite (Mot) scores were analyzed. RESULTS: The means [SD] of C-A DQ, L-S DQ, P-M DQ, and overall DQ of KSPD were 94 [15], 90 [17], 89 [15], and 93 [14], respectively. The means [SD] of the Cog, Lang, and Mot scores of Bayley III were 96 [13], 84 [12], and 91 [12], respectively. The DQ of KSPD strongly correlated with the corresponding composite score of Bayley III; Spearman rank correlations between the Cog score and C-A DQ, the Lang score and L-S DQ, and the Mot score and P-M DQ were 0.65, 0.71 and 0.55, respectively. The selected cut-off of the Cog score of <85 accurately identified development delay, defined by KSPD, with sensitivity of 100% and specificity of 85%. CONCLUSION: Although absolute value of the Bayley III score may not represent the degree of impairment, the developmental characteristics on KSPD well correlated with those on Bayley III. The developmental outcomes of Japanese VLBW infants were verified by the two tests.


Subject(s)
Child Development , Developmental Disabilities/diagnosis , Infant, Premature/psychology , Infant, Very Low Birth Weight/psychology , Neuropsychological Tests , Psychiatric Status Rating Scales , Female , Humans , Infant , Infant, Newborn , Male , Reproducibility of Results , Sensitivity and Specificity
15.
Diabetes ; 65(3): 755-67, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26384385

ABSTRACT

Overcoming refractory massive proteinuria remains a clinical and research issue in diabetic nephropathy. This study was designed to investigate the pathogenesis of massive proteinuria in diabetic nephropathy, with a special focus on podocyte autophagy, a system of intracellular degradation that maintains cell and organelle homeostasis, using human tissue samples and animal models. Insufficient podocyte autophagy was observed histologically in patients and rats with diabetes and massive proteinuria accompanied by podocyte loss, but not in those with no or minimal proteinuria. Podocyte-specific autophagy-deficient mice developed podocyte loss and massive proteinuria in a high-fat diet (HFD)-induced diabetic model for inducing minimal proteinuria. Interestingly, huge damaged lysosomes were found in the podocytes of diabetic rats with massive proteinuria and HFD-fed, podocyte-specific autophagy-deficient mice. Furthermore, stimulation of cultured podocytes with sera from patients and rats with diabetes and massive proteinuria impaired autophagy, resulting in lysosome dysfunction and apoptosis. These results suggest that autophagy plays a pivotal role in maintaining lysosome homeostasis in podocytes under diabetic conditions, and that its impairment is involved in the pathogenesis of podocyte loss, leading to massive proteinuria in diabetic nephropathy. These results may contribute to the development of a new therapeutic strategy for advanced diabetic nephropathy.


Subject(s)
Apoptosis , Autophagy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetic Nephropathies/metabolism , Kidney/metabolism , Podocytes/metabolism , Proteinuria/metabolism , Adult , Aged , Animals , Autophagy-Related Protein 5 , Autophagy-Related Protein 7 , Blotting, Western , Cell Line , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Diabetic Nephropathies/etiology , Diabetic Nephropathies/pathology , Diet, High-Fat , Female , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Intravital Microscopy , Kidney/pathology , Lysosomes/metabolism , Lysosomes/pathology , Male , Membrane Proteins/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Microfilament Proteins/metabolism , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Microtubule-Associated Proteins/genetics , Middle Aged , Proteinuria/etiology , Proteinuria/pathology , RNA-Binding Proteins/blood , Rats , Rats, Long-Evans , Severity of Illness Index , Young Adult
16.
Clin J Am Soc Nephrol ; 10(12): 2152-8, 2015 Dec 07.
Article in English | MEDLINE | ID: mdl-26563378

ABSTRACT

BACKGROUND AND OBJECTIVES: We investigated the association of urinary potassium and sodium excretion with the incidence of renal failure and cardiovascular disease in patients with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 623 Japanese type 2 diabetic patients with eGFR≥60 ml/min per 1.73 m(2) were enrolled in this observational follow-up study between 1996 and 2003 and followed-up until 2013. At baseline, a 24-hour urine sample was collected to estimate urinary potassium and sodium excretion. The primary end point was renal and cardiovascular events (RRT, myocardial infarction, angina pectoris, stroke, and peripheral vascular disease). The secondary renal end points were the incidence of a 50% decline in eGFR, progression to CKD stage 4 (eGFR<30 ml/min per 1.73 m(2)), and the annual decline rate in eGFR. RESULTS: During the 11-year median follow-up period, 134 primary end points occurred. Higher urinary potassium excretion was associated with lower risk of the primary end point, whereas urinary sodium excretion was not. The adjusted hazard ratios for the primary end point in Cox proportional hazards analysis were 0.56 (95% confidence interval [95% CI], 0.33 to 0.95) in the third quartile of urinary potassium excretion (2.33-2.90 g/d) and 0.33 (95% CI, 0.18 to 0.62) in the fourth quartile (>2.90 g/d) compared with the lowest quartile (<1.72 g/d). Similar associations were observed for the secondary renal end points. The annual decline rate in eGFR in the fourth quartile of urinary potassium excretion (-1.3 ml/min per 1.73 m(2)/y; 95% CI, -1.5 to -1.0) was significantly slower than those in the first quartile (-2.2; 95% CI, -2.4 to -1.8). CONCLUSIONS: Higher urinary potassium excretion was associated with the slower decline of renal function and the lower incidence of cardiovascular complications in type 2 diabetic patients with normal renal function. Interventional trials are necessary to determine whether increasing dietary potassium is beneficial.


Subject(s)
Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Diabetic Nephropathies/etiology , Kidney/physiopathology , Potassium/urine , Renal Elimination , Renal Insufficiency/epidemiology , Aged , Biomarkers/urine , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/physiopathology , Cardiovascular Diseases/urine , Chi-Square Distribution , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/urine , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/physiopathology , Diabetic Nephropathies/urine , Disease Progression , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Incidence , Japan/epidemiology , Kaplan-Meier Estimate , Linear Models , Male , Middle Aged , Natriuresis , Prognosis , Proportional Hazards Models , Prospective Studies , Protective Factors , Renal Insufficiency/diagnosis , Renal Insufficiency/physiopathology , Renal Insufficiency/urine , Risk Factors , Sodium/urine , Time Factors
17.
Free Radic Biol Med ; 89: 831-41, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26482866

ABSTRACT

Free fatty acid-bound albumin (FFA-albumin)-related oxidative stress is involved in the pathogenesis of proximal tubular cell (PTC) damage and subsequent renal dysfunction in patients with refractory proteinuria. Nicotinamide adenine dinucleotide (NAD) metabolism has recently been focused on as a novel therapeutic target for several modern diseases, including diabetes. This study was designed to identify a novel molecule in NAD metabolism to protect PTCs from lipotoxicity-related oxidative stress. Among 19 candidate enzymes involved in mammalian NAD metabolism, the mRNA expression level of nicotinamide n-methyltransferase (NNMT) was significantly increased in both the kidneys of FFA-albumin-overloaded mice and cultured PTCs stimulated with palmitate-albumin. Knockdown of NNMT exacerbated palmitate-albumin-induced cell death in cultured PTCs, whereas overexpression of NNMT inhibited it. Intracellular concentration of 1-Methylnicotinamide (1-MNA), a metabolite of NNMT, increased and decreased in cultured NNMT-overexpressing and -knockdown PTCs, respectively. Treatment with 1-MNA inhibited palmitate-albumin-induced mitochondrial reactive oxygen species generation and cell death in cultured PTCs. Furthermore, oral administration of 1-MNA ameliorated oxidative stress, apoptosis, necrosis, inflammation, and fibrosis in the kidneys of FFA-albumin-overloaded mice. In conclusion, NNMT-derived 1-MNA can reduce lipotoxicity-mediated oxidative stress and cell damage in PTCs. Supplementation of 1-MNA may have potential as a new therapy in patients with refractory proteinuria.


Subject(s)
Kidney Tubules, Proximal/pathology , Niacinamide/analogs & derivatives , Nicotinamide N-Methyltransferase/metabolism , Oxidative Stress/physiology , Proteinuria/complications , Albumins/toxicity , Animals , Blotting, Western , Disease Models, Animal , Fatty Acids, Nonesterified/toxicity , Immunohistochemistry , Kidney Tubules, Proximal/metabolism , Male , Mice , Mice, Inbred C57BL , Niacinamide/metabolism , RNA, Small Interfering , Real-Time Polymerase Chain Reaction , Transfection
18.
Intern Med ; 54(17): 2213-7, 2015.
Article in English | MEDLINE | ID: mdl-26328649

ABSTRACT

We report a case involving a 43-year-old Japanese woman with steroid-resistant focal segmental glomerular sclerosis (FSGS) and severe renal dysfunction, which was ameliorated by low-density lipoprotein apheresis (LDL-A). She had been treated with steroid therapy, but had experienced anuria for over 10 weeks and required hemodialysis. She was then treated with LDL-A, which resulted in improved urinary protein excretion and renal function. Her renal function recovered after 97 days of hemodialysis therapy. This case suggests that LDL-A may represent an effective rescue treatment in patients with FSGS and long-term anuria.


Subject(s)
Anuria/etiology , Glomerulosclerosis, Focal Segmental/therapy , Lipoproteins, LDL/blood , Nephrotic Syndrome/therapy , Plasmapheresis , Renal Dialysis , Adrenal Cortex Hormones/administration & dosage , Adult , Drug Resistance , Female , Glomerulosclerosis, Focal Segmental/blood , Glomerulosclerosis, Focal Segmental/complications , Humans , Kidney/metabolism , Kidney/pathology , Nephrotic Syndrome/blood , Nephrotic Syndrome/etiology , Treatment Outcome
19.
Biochem Biophys Res Commun ; 465(2): 249-55, 2015 Sep 18.
Article in English | MEDLINE | ID: mdl-26271596

ABSTRACT

Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes.


Subject(s)
Adipose Tissue, Brown/metabolism , Diabetes Mellitus, Experimental/prevention & control , Energy Metabolism/genetics , Glycogen Storage Disease Type IIb/genetics , Lysosomal-Associated Membrane Protein 2/metabolism , Lysosomes/metabolism , Adipose Tissue, Brown/pathology , Animals , Autophagy/genetics , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/etiology , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Diet, High-Fat , Dietary Fats/adverse effects , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Gene Expression , Glycogen Storage Disease Type IIb/metabolism , Lysosomal-Associated Membrane Protein 2/genetics , Lysosomes/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , PPAR alpha/genetics , PPAR alpha/metabolism , Phagosomes/metabolism , Phagosomes/pathology , Protective Factors , RNA, Messenger/genetics , RNA, Messenger/metabolism
20.
Angew Chem Int Ed Engl ; 54(25): 7336-9, 2015 Jun 15.
Article in English | MEDLINE | ID: mdl-25940278

ABSTRACT

Reaction of O2 with a high-spin mononuclear iron(II) complex supported by a five-azole donor set yields the corresponding mononuclear non-heme iron(III)-superoxo species, which was characterized by UV/Vis spectroscopy and resonance Raman spectroscopy. (1)H NMR analysis reveals diamagnetic nature of the superoxo complex arising from antiferromagnetic coupling between the spins on the low-spin iron(III) and superoxide. This superoxo species reacts with H-atom donating reagents to give a low-spin iron(III)-hydroperoxo species showing characteristic UV/Vis, resonance Raman, and EPR spectra.


Subject(s)
Azoles/chemistry , Ferric Compounds/chemistry , Oxygen/chemistry , Superoxides/chemistry , Cobalt/chemistry , Ligands , Models, Molecular
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