NT-pro BNP level at dialysis initiation is a useful biomarker for predicting hospitalization for ischemic heart disease.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD. METHODS: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed. RESULTS: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL. CONCLUSION: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD. TRIAL REGISTRATION: UMIN000010806.

Chiral Recognition of Diketopiperazine Containing Proline Residues by (-)-Epigallocatechin-3-O-gallate in Water.

The stoichiometry and precipitate yield of a complex of (-)-epigallocatechin-3-O-gallate (EGCg) and cyclo(Pro-Xxx) (Xxx = phenylalanine (Phe), tyrosine (Tyr)) were evaluated using integrated values of their proton signals by quantitative 1H-NMR (q NMR). It was determined to be a 1 : 1 complex of EGCg and cyclo(Pro-Xxx). The change in the chemical shift value of proton signals of cyclo(Pro-Xxx) in 1H-NMR spectra by adding standard amounts of EGCg was investigated. Differences in chemical shift values of H8α, H7αß, H8ß, H10, H9, and H3 proton signals between cyclo(L-Pro-L-Phe) and cyclo(D-Pro-D-Phe), and those of H8α, H7αß, H8ß, H10, H9, H3, and H13 proton signals between cyclo(L-Pro-L-Tyr) and cyclo(D-Pro-D-Tyr) were observed as a significant difference at 54 mmol/L of EGCg. It was found that their chirality was clearly recognized by EGCg. The significant difference in the change of the chemical shift value of H8α proton signals between cyclo(L-Pro-L-Xxx) and cyclo(D-Pro-D-Xxx) was the largest, and the difference was considered to have resulted from the difference in the ratio of extended conformer in equilibrium between folded and extended conformers. Such a significant difference in change values between cyclo(L-Pro-D-Xxx) and cyclo(D-Pro-L-Xxx) was not observed due to a rigid intramolecular CH-π interaction. EGCg did not clearly recognize the chirality of cyclo(L-Pro-D-Xxx) and cyclo(D-Pro-L-Xxx).

Oral Iron Absorption of Ferric Citrate Hydrate and Hepcidin-25 in Hemodialysis Patients: A Prospective, Multicenter, Observational Riona-Oral Iron Absorption Trial.

Oral ferric citrate hydrate (FCH) is effective for iron deficiencies in hemodialysis patients; however, how iron balance in the body affects iron absorption in the intestinal tract remains unclear. This prospective observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406) was conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables with respect to ΔFe2h, and the secondary outcome was the description of the predictors of the body's iron balance. Generalized estimating equations (GEEs) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and TSAT decreased (-0.459, -0.643 to -0.276, p = 0.000; -0.648, -1.099 to -0.197, p = 0.005, respectively) in GEEs. FTN increased when RBCs decreased (-1.392, -1.749 to -1.035, p = 0.000) and hepcidin-25 increased (0.297, 0.239 to 0.355, p = 0.000). Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC iron to FTN iron, inhibiting iron absorption even with continued FCH intake.

Quantification of Risperidone Contained in Precipitates Produced by Tea Catechins Using Nuclear Magnetic Resonance.

A mixture of risperidone and eight major tea catechins: (-)-epicatechin-3-O-gallate (ECg), (-)-epigallocatechin-3-O-gallate (EGCg), (-)-catechin-3-O-gallate (Cg), (-)-gallocatechin-3-O-gallate (GCg), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (+)-catechin (CA), or (+)-gallocatechin (GC), in tartaric acid buffer (pH 3.0) afforded a precipitate. Amounts of risperidone and these catechins in the precipitate were measured by quantitative 1H-NMR (qNMR). About half or more of risperidone used was precipitated by gallated catechins ECg, EGCg, Cg, and GCg; on the other hand, it was precipitated little by non-gallated catechins EC, EGC, CA, and GC. Furthermore, risperidone was precipitated more by 2,3-trans gallated catechins Cg and GCg than 2,3-cis gallated catechins ECg and EGCg. Regarding the amount of tea catechins in the precipitate obtained by a mixture of risperidone and Catechin Mixture, the amounts of 2,3-cis gallated catechins EGCg and ECg were much larger than those of the other green tea catechins GCg, EC, EGC, CA, and GC. It was considered that risperidone was mainly precipitated by EGCg and ECg in Catechin Mixture. Therefore, it can be concluded that when patients take risperidone with catechin-rich beverages, the efficacy of risperidone reduces, mainly because the 2,3-cis gallated catechins EGCg and ECg form complexes with risperidone and precipitate.

Study protocol and baseline characteristics of newly induced dialysis patients: a prospective multi-center cohort study with a biological sample bank, the Ibaraki Dialysis Initiation Cohort (iDIC) study.

BACKGROUND: Patients with end-stage kidney disease (ESKD) face higher risks of life-threatening events including cardiovascular disease. Various risk factors are identified as agents influencing the life prognosis of ESKD patients. Herein, we evaluated the risk factors related to the outcomes of Japanese patients with dialysis induction. We present the study protocol, the patients' baseline characteristics, and their outcomes. METHODS: The Ibaraki Dialysis Initiation Cohort (iDIC) Study is a prospective multi-center cohort study in collaboration with 60 tertiary-care facilities in Ibaraki Prefecture, Japan. We collected baseline data from clinical records and analyzed blood and urine samples of these facilities' patients with diabetic nephropathy, hypertensive nephrosclerosis, and chronic glomerulonephritis (CGN). The study's primary outcome was the survival rate at 24 months after dialysis induction. We performed a Kaplan-Meier analysis for cumulative survival and a Cox proportional hazards analysis for all-cause mortality and hospitalization. RESULTS: We analyzed 636 patients' cases (424 males, 212 females, age 67.4 ± 13.1 yrs. [mean ± SD]). We compared the patients' baseline data with those of similar cohort studies. As the primary kidney disease, 327 cases (51.4%) were diagnosed as diabetic nephropathy, 101 (15.9%) as hypertensive nephrosclerosis, and 114 (17.9%) as CGN. The mean serum creatinine value was 9.1 ± 2.9 mg/dL. The mean estimated glomerular filtration rate was 5.6 ± 1.8 mL/min/1.73m2. The cumulative survival rates at 6 months and 24 months after dialysis induction were 95.2 and 87.7%, respectively. The cumulative survival rate was significantly lower with increasing age. A Cox proportional hazards regression analysis demonstrated that high age was significantly associated with all-cause mortality. CONCLUSIONS: Regarding the clinical characteristics of these newly induced dialysis patients, the same trend as in other cohort studies was observed. Another study is underway to explore prognostic factors based on the iDIC Study's findings.

Levels of Soluble NKG2D Ligands and Cancer History in Patients Starting Hemodialysis.

Background: Immune dysfunction in hemodialysis patients is partially due to NK cell impairment. Ligands for NK activating receptors such as NKG2D expressed on cancer cells are involved in NK cell dysfunction and can lead to cancer development. Methods: A cohort with 370 patients who started hemodialysis (HD) was investigated. Serum levels of soluble NKG2D ligands were measured. Cancer history was defined as any cancer diagnosis at induction and hospitalization and death due to cancer during 2-year follow-up. Results: Sixty-two patients with and 308 patients without a cancer history showed mostly comparable biochemical parameters and uremic status at HD induction. Soluble MICB, ULBP-1, and ULBP-2 were detected in sera from most patients starting HD rather than MICA, the most representative NKG2D ligand. Measured NKG2D ligands, except for ULBP-1, were strongly correlated with each other. Correlations between NKG2D ligands and renal function were significant but modest in patients starting HD. Cancer history did not have any impact on levels of soluble NKG2D ligands. Discussion: Even though this investigation lacked a control cohort and serial measurement of parameters, expression patterns of NKG2D ligands were comprehensively described, and the significance of cancer in patients starting HD was elucidated for the first time. Elevated levels of soluble NKG2D ligands occurred potentially due to complex mechanisms of oxidative stress, with insufficient metabolism and excretion in a uremic milieu, but they might mask the significance of elevations in serum levels of soluble NKG2DLs in patients with a cancer history.

Analysis of the isomerization of diketopiperazine consisting of proline and aromatic amino acid residues using nuclear magnetic resonance.

Under different concentrations of the base potassium deuteroxide KOD, the progress of reactions, such as enolization, D-substitution, isomerization, and conformational changes of diketopiperazine cyclo(L-Pro-L-Xxx) and cyclo(D-Pro-L-Xxx) (Xxx = Phe, Tyr) in D2O solution, was investigated by 1H nuclear magnetic resonance (NMR). Cyclo(L-Pro-L-Xxx) is mostly isomerized to cyclo(D-Pro-L-Xxx) in D2O solution, whereas cyclo(D-Pro-L-Xxx) is only slightly isomerized to cyclo(L-Pro-L-Xxx) even under stronger basic conditions. After adding a deuterated organic solvent (CD3COCD3, CD3SOCD3 or CD3OD) to a D2O solution of cyclo(L-Pro-L-Xxx), cyclo(D-Pro-L-Xxx), or increasing the temperature of the D2O solution, CH-π interaction between H9 and the benzene ring of cyclo (D-Pro-L-Xxx) was stronger than that between H8α and the benzene ring of cyclo(L-Pro-L-Xxx).

Molecular Capture and Conformational Change of Diketopiperazines Containing Proline Residues by Epigallocatechin-3-O-gallate in Water.

The addition of an aqueous solution of diketopiperazine cyclo(Pro-Xxx) (Xxx: amino acid residue) to an aqueous solution of (-)-epigallocatechin-3-O-gallate (EGCg) led to precipitation of the complex of EGCg and cyclo(Pro-Xxx). The molecular capture abilities of cyclo(Pro-Xxx) using EGCg were evaluated by the ratio of the amount of cyclo(Pro-Xxx) included in the precipitates of the complex with EGCg to that of the total cyclo(Pro-Xxx) used. Stronger hydrophobicity of the side chain of the amino acid residue of cyclo(Pro-Xxx) led to a higher molecular capture ability. Furthermore, the molecular capture ability decreased when the side chain of the amino acid residue had a hydrophilic hydroxyl group. When diketopiperazine cyclo(Pro-Xxx), excluding cyclo(D-Pro-L-Ala), was taken into the hydrophobic space formed by the three aromatic A, B, and B' rings of EGCg, and formed a complex, their conformation was maintained in the hydrophobic space. Based on nuclear Overhauser effect (NOE) measurement, the 3-position methyl group of cyclo(D-Pro-L-Ala) in D2O was axial, whereas that of cyclo(L-Pro-L-Ala) was equatorial. When cyclo(D-Pro-L-Ala) was taken into the hydrophobic space of EGCg and formed a 2 : 2 complex, its 3-position methyl group changed from the axial position to the equatorial position due to steric hindrance by EGCg.

Development of High-Order Functions Using (-)-Epigallocatechin-3-O-gallate in Water.

The high-order functions of molecular capture and chiral recognition of tea gallated catechins (-)-epigallocatechin-3-O-gallate (EGCg) in water were investigated. A solution of equimolar amounts of a variety of heterocyclic compounds and EGCg in water afforded adhesive precipitates containing the heterocyclic compounds and EGCg at a molar ratio of 1 : 1, based on the integrated value of NMR proton signals. The molecular capture abilities of a variety of heterocyclic compounds using EGCg from the aqueous solutions were evaluated with the ratios of the heterocyclic compounds included in the precipitates of EGCg complex to the total heterocyclic compounds used. In the 1H-NMR spectrum of a solution containing cyclo(L-Pro-Gly), cyclo(D-Pro-Gly), and EGCg in a D2O solution, a difference in the chemical shift of the 1H-NMR signal for some protons of the Pro residue was observed. Judging from the crystal structures of the 2 : 2 EGCg complexes of cyclo(L-Pro-Gly), cyclo(D-Pro-Gly), the difference in the chemical shift derived mainly from a magnetic anisotropic shielding effect by the ring current from the B ring of EGCg.In the 1H-NMR spectrum of a solution containing the pharmaceuticals racemic (R,S)-propranolol, (R,S)-diprophylline, (R,S)-proxyphylline and EGCg in D2O, splitting of the 1H-NMR signals of the pharmaceuticals was observed. It was suggested that the pharmaceuticals formed diastereomers of EGCg complexes, as a result chirality of the pharmaceuticals was recognized by EGCg in the D2O solution.

Molecular Capture Using the Precipitate of Creaming-Down by (-)-Epigallocatechin-3-O-gallate.

An aqueous solution of equimolecular amounts of 2-chloropyrimidine and (-)-epigallocatechin-3-O-gallate (EGCg) afforded a colorless block crystal, which was determined to be a 2 : 2 complex of 2-chloropyrimidine and EGCg by X-ray crystallographic analysis. The 2 : 2 complex was formed by the cooperative effect of three intermolecular interactions, π-π and CH-π interactions, and intermolecular hydrogen bonds. Upon formation of the 2 : 2 complex, a 2-chloropyrimidine molecule was captured by a hydrophobic space formed by the three aromatic rings of A, B, and B' rings of two EGCg molecules. The molecular capture abilities of various heterocyclic compounds using EGCg were evaluated by ratio of the heterocyclic compounds included in the precipitates of complex of EGCg to the heterocyclic compounds used. The amount of the heterocyclic compounds was measured by an integrated value of corresponding proton signals in the quantitative 1H-NMR spectrum.

Chiral Recognition of Pharmaceuticals Having a Xanthine Skeleton by (-)-Epigallocatechin-3-O-gallate in Water.

A mixture of pharmaceuticals having a xanthine skeleton, theophylline, proxyphylline, diprophylline and (-)-epigallocatechin-3-O-gallate (EGCg) in water created a sticky precipitates, which were thought to be 2 : 2 complexes of the pharmaceuticals and EGCg. The molecular capture ability of the pharmaceuticals having a xanthine skeleton by EGCg was estimated by the amount of the pharmaceuticals included in the precipitates of the complexes, and measured by the integrated value of proton signals in the quantitative 1H-NMR spectra. Based on changes in chemical shifts of proton signals of the pharmaceuticals with a xanthine skeleton in 1H-NMR spectra by adding standard amounts of EGCg, the xanthine skeleton of the pharmaceuticals was considered to exist in the hydrophobic space formed by the three aromatic A, B, B' rings of EGCg, and a part of the proxyphylline and diprophylline side chains existed out of the hydrophobic space. In the 1H-NMR spectra of the mixture of (R)- and (S)-proxyphylline, (R)- and (S)-diprophylline and an equimolecular amount of EGCg, the N3-CH3 signal of (R)- and (S)-proxyphylline, and (R)- and (S)-diprophylline was clearly observed as two singlets. This suggested that EGCg recognized the chirality of proxyphylline and diprophylline in water.

Subclavian steal syndrome in a hemodialysis patient after percutaneous transluminal angioplasty of arteriovenous access.

INTRODUCTION: We describe a hemodialysis patient who developed subclavian steal syndrome via an arteriovenous fistula after percutaneous transluminal angioplasty. CASE DESCRIPTION: A 55-year-old female with end-stage renal failure due to polycystic kidney disease had been treated with hemodialysis for 10 years. Because of an autologous arteriovenous fistula stenosis, percutaneous transluminal angioplasty was performed. After successful treatment with percutaneous transluminal angioplasty, the patient developed dizziness. Magnetic resonance imaging with angiography of the brain and neck revealed normal bilateral subclavian and carotid arteries. However, flow in the left vertebral artery was not detected in time-of-flight magnetic resonance angiography. The left vertebral artery showed completely reversed blood flow as detected by color duplex ultrasound. We also confirmed anterograde flow in the left vertebral artery by color duplex ultrasound with arteriovenous fistula compression. Arteriovenous flows before the arteriovenous fistula stenosis and post-percutaneous transluminal angioplasty were 1146 and 2239 mL/min, respectively. These findings suggested high-flow arteriovenous fistula led to the subclavian steal syndrome. The patient was subsequently treated by a flow reduction in the high-flow arteriovenous access using a modified graft inclusion technique. We decreased the arteriovenous fistula flow to 851 mL/min, which remained under 850 mL/min, 1 year later. The brain natriuretic peptide level and right-ventricular pressure also decreased after treatment. A modified graft inclusion technique was successful in decreasing the high flow of the arteriovenous fistula, and improved subclavian steal syndrome symptom and cardiac overload. CONCLUSION: This case shows that percutaneous transluminal angioplasty for an arteriovenous fistula may induce subclavian steal syndrome, and a modified graft inclusion technique was useful in improving the high flow of an arteriovenous fistula.

Conformational Change and Epimerization of Diketopiperazines Containing Proline Residue in Water.

In water, diketopiperazines cyclo(L-Pro-L-Xxx) and cyclo(L-Pro-D-Xxx) (Xxx=Phe, Tyr) formed an intramolecular hydrophobic interaction between the main skeleton part and their benzene ring, and both cyclo(L-Pro-L-Xxx) and cyclo(L-Pro-D-Xxx) took a folded conformation. The conformational changes from folded to extended conformation by addition of several deuterated organic solvents (acetone-d6, metanol-d4, dimethyl sulfoxide-d6 (DMSO-d6)) and the temperature rise were investigated using 1H-NMR spectra. The results suggested that the intrarmolecular hydrophobic interaction of cyclo(L-Pro-D-Xxx) formed more strongtly than that of cyclo(L-Pro-L-Xxx). Under a basic condition of 1.0×10-1 mol/L potassium deuteroxide, enolization of O1-C1-C9-H9 moiety of cyclo(L-Pro-L-Xxx) occurred, while that of the O4-C4-C3-H3 moiety did not. Cyclo(L-Pro-L-Xxx) epimerized to cyclo(D-Pro-L-Xxx), while cyclo(L-Pro-D-Xxx) did not change.

Mechanism of Creaming Down Based on Chemical Characterization of a Complex of Caffeine and Tea Catechins.

The component of a precipitate resulting from creaming down, which was made from caffeine and a catechin mixture, was determined by an integrated value of H2 proton signals of tea catechins in the quantitative (1)H-NMR spectrum. The results showed that gallate-type catechins formed a precipitate by creaming down more predominantly than non-gallate-type catechins. X-ray crystallographic analysis showed that the gallate-type catechin (-)-epigallocatechin-3-O-gallate (EGCg), (-)-epicatechin-3-O-gallate (ECg) formed 2 : 2 and 2 : 4 complexes with caffeine, respectively, and the non-gallate-type catechin (-)-epicatechin (EC) and caffeine formed a 1 : 1 complex. The 2 : 2, 2 : 4 complexes of caffeine and EGCg, ECg formed a hydrophobic space with three aromatic A, B, and B' rings of two EGCg, ECg molecules, and one caffeine molecule was captured in this hydrophobic space. However, no such hydrophobic space in the 1 : 1 complex of caffeine and EC formed. It was thought that the hydrophobicity of the 2 : 2, 2 : 4 complexes of caffeine and EGCg, ECg was stronger than that of the 1 : 1 complex of caffeine and EC, with the result that the 2 : 2, 2 : 4 complexes of caffeine and EGCg, ECg precipitated by creaming down more predominantly than the 1 : 1 complex of caffeine and EC in an aqueous solution. Furthermore, the molecular capture of various heterocyclic compounds by formation of the 2 : 2 complex of EGCg from the aqueous solution was investigated using the quantitative (1)H-NMR spectrum.

Temporal Changes in Post-Infectious Glomerulonephritis in Japan (1976-2009).

BACKGROUND: The incidence of post-infectious glomerulonephritis (PIGN) in developed countries has decreased over the last 50 years. Here we identified the trends of the incidence of PIGN in Japan during the past four decades. METHODS: We explored the frequency, clinicopathological findings, and prognosis of PIGN based on 6,369 cases from the Renal Biopsy Database of our institute in the Kanto region of Japan, diagnosed histologically from 1976 to 2009. RESULTS: The numbers of PIGN cases were 131 (2.1%) in total, and 2.4%, 1.1%, 2.6% and 2.1% identified in the 1970s, 1980s, 1990s, and 2000s, respectively. Acute glomerulonephritis (AGN), including post-streptococcal glomerulonephritis (PSGN), accounted for almost all of the PIGN cases in the 1970s, but decreased to approx. 40%-50% since the 1990s. In the 1990s, Staphylococcus aureus infection-related nephritis (SARN) showed a rapid increase in rate, reaching 30%. The incidence of hepatitis C virus infection-associated GN (HCVGN) has increased since the 1990s. The average age at onset rose from 33 to 51 years over the study period. These transitions can be summarized as increases in SARN and HCVGN and decreases in PSGN and other types of AGN, since SARN and HCVGN have older onsets compared to PSGN and other AGN types. The clinicopathological features were marked for each PIGN. Regarding the prognosis, the renal death rates of both the SARN and HCVGN groups were significantly higher than those of other PIGN. CONCLUSION: Based on our analysis of the Renal Biopsy Database, the incidence of PIGN in Japan reached its peak in the 1990s. The temporal changes in the incidence of PIGN reflected the trends in infectious diseases of each decade and the continual aging of the population, with a related higher susceptibility to infections.

Chiral Recognition of Diketopiperazine Cyclo(Pro-Gly) and Propranolol Using (-)-Epigallocatechin-3-O-gallate.

In the (1)H-NMR spectrum of a solution containing an equimolecular amount of cyclo(L-Pro-Gly), cyclo(D-Pro-Gly) and (-)-epigallocatechin-3-O-gallate (EGCg) in a D2O, a difference in the chemical shift of (1)H-NMR signal for H7α, H7ß,8α of the Pro residue was observed. Judging from the crystal structures of the 2 : 2 complexes of EGCg and cyclo(L-Pro-Gly), cyclo(D-Pro-Gly), the difference in the chemical shift resulted mainly from a magnetic anisotropic shielding effect by the ring current from the B ring of EGCg. Therefore, it was considered that chirality of cyclo(Pro-Gly) was recognized by EGCg in the D2O solution. Furthermore, in the (1)H-NMR spectrum of a solution containing an equimolecular amount of racemic propranolol ((R)- and (S)-propranolols) and EGCg in D2O, the (1)H-NMR signal for H2 of the naphthalene group was observed as two doublets, suggesting that the racemic propranolol formed diastereomers of complexes with EGCg; as a result, chirality of propranolol was recognized by EGCg in the D2O solution.

Properties of precipitate of creaming down by (-)-epigallocatechin-3-O-gallate and caffeine.

An aqueous solution of equimolecular amounts of gallated catechin (-)-epigallocatechin-3-O-gallate (EGCg) and caffeine afforded a crude precipitate by creaming, which crystallized slowly for about three months at 10°C to give a colorless block crystal. The crystal was determined to be a 2 : 2 complex of EGCg and caffeine by X-ray crystallographic analysis. The 2 : 2 complex was formed with the cooperative effect of three intermolecular interactions, π-π and CH-π interactions, and intermolecular hydrogen bonds. Upon formation of the 2 : 2 complex, a caffeine molecule was captured by a hydrophobic space formed by the aromatic rings A, B, and B' rings of two EGCg molecules. Judging from the entropy value, the shift value in the chemical shift of proton signals in (1)H-NMR spectra, the NT1 value, and nuclear Overhauser effects (NOEs), it was thought that the structure of complexes of EGCg and caffeine in aqueous solution were the same as their crystal structure.

Quantum chemical study for radical-induced DNA effects and damage.

Differences in molecular interaction between bases (adenine (A), guanine (G), and cytosine (C)) and the methyl (Me)-radical were investigated by perturbation analysis using the quantum chemical method. Part of the source of damage to the DNA was elucidated at the molecular level. In the reaction of each of the saccharide derivatives (dA, dG, and dC) with Me-radical, the reactivity of dG (≈dA) is more than about 10 times larger than that of dC. Therefore, it is expected that the base G (and A) was more than about 10 times than the base C in radical-reactivity of the base. For the reaction of dA and dG with the radical, the C(8) site of the partial purine ring of dA and dG, and the C(5) site of the pyrimidine ring of dC were the main reaction sites for methylation. In the reaction of DNA composed of hydrogen-bonded base pairs G-C and A-T with the radical, the purine ring in the constituent base G reacted preferentially with the radical to yield 8-methyl-guanines.

Efficacy of continuous oral administration of lanthanum carbonate over 24 months.

To examine the efficacy of long-term administration of lanthanum carbonate, changes in serum Ca, phosphate, whole parathyroid hormone (wPTH), and ALP were examined in 40 patients who were able to tolerate dosage of lanthanum carbonate over a continuous period of 24 months. Concurrently, concomitant administration of other phosphate binders, cinacalcet, vitamin D, etc., was also examined. After 24 months, serum phosphorus levels (P levels) had decreased to within management target of guidelines, from 6.16 ± 1.44 mg/dL to 5.58 ± 1.15 mg/dL, and this effect was maintained for 2 years. There were no changes in Ca level. wPTH did not change significantly but tended to increase at 12 months. The dose of concomitantly administered calcium carbonate and sevelamer hydrochloride was reduced. The P-lowering function of lanthanum carbonate still held steady at 24 months following the start of dosage. Because of the rising trend seen in wPTH, dose of cinacalcet and/or vitamin D need to be modulated. Reducing the number of concomitantly administered phosphate binder tablets was desirable from the standpoint of patient adherence.

Primary membranoproliferative glomerulonephritis on the decline: decreased rate from the 1970s to the 2000s in Japan.

BACKGROUND: A prolonged change in the rate of primary membranoproliferative glomerulonephritis (MPGN) was identified using a Japanese database of renal biopsies. METHODS: We retrospectively investigated 6,369 renal biopsies that were performed between 1976 and 2009. Primary MPGN patients were selected, and the clinical and pathological findings were examined. We also statistically analyzed the changing rate of the onset of primary MPGN according to each decade. RESULTS: Seventy-nine cases with primary MPGN (1.2 % of total biopsies) were diagnosed. The age of the patients ranged from 6-79 years (average 34.6 years). There were 24 children and 55 adults, including 37 male and 42 female patients. Thirty-six cases of primary MPGN (45.6 %) showed nephrotic syndrome-8 childhood and 28 adult cases. In the pathological classification of 44 samples using electron microscopy, 29 cases were MPGN type I, 1 case was MPGN type II, and 14 cases were MPGN type III. The secular change of the rate of primary MPGN onset showed a statistically significant reduction from the 1970s to the 2000s. The rate of primary MPGN onset in the child population also significantly decreased, but not in the adult population. Among the clinical parameters, disease severity and prognosis remained unchanged. Regarding treatment in recent years, steroid pulse therapy became more available but the administration of warfarin and anti-platelet drugs significantly decreased. CONCLUSION: We concluded that the rate of total primary MPGN and that of pediatric patients with primary MPGN decreased.