Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: Effects of ACEI and ARB

Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: Effects of ACEI and ARB.BackgroundAngiotensin II (Ang II) can up-regulate nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase, whose product superoxide anion (O2-) can interact with nitric oxide (NO) to form peroxynitrite (ONOO-). We tested the hypothesis that Ang II subtype 1 (AT1) receptor activation enhances oxidative stress and nitrotyrosine deposition in the kidneys of rats with diabetes mellitus (DM).MethodsAfter two weeks of streptozotocin-induced DM, rats received either no treatment, an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) for two weeks. At four weeks, renal expression of the p47phox component of NAD(P)H oxidase, endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and nitrotyrosine were evaluated by Western blot and immunohistochemistry and related to plasma lipid peroxidation products (LPO), hydrogen peroxide production in the kidney and 24-hour protein excretion.ResultsImmunoreactive expression of p47phox and eNOS were increased in DM with an increase in plasma LPO, renal hydrogen peroxide production and nitrotyrosine deposition. Expression of nNOS was unaltered. Treatment with either ACEI or ARB prevented all these findings and also prevented significant microalbuminuria. The treatments did not affect the elevated blood sugar, nor did DM or its treatment affect the blood pressure or the creatinine clearance.ConclusionEarly proteinuric diabetic nephropathy increases renal expression of the p47phox component of NAD(P)H oxidase and eNOS with increased indices of systemic and renal oxidative/nitrosative stress. An ACEI or an ARB prevents these changes and prevents the development of proteinuria, independent of blood pressure or blood sugar. This finding indicates a pathogenic role for AT1 receptors in the development of oxidative damage in the kidneys during early DM

Effects of NADPH oxidase inhibitor in diabetic nephropathy

Effects of NADPH oxidase inhibitor in diabetic nephropathy.BackgroundWe used apocynin to test the hypothesis that superoxide anion (O−2) from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase underlies the development of diabetic nephropathy in the rat.MethodsRats received apocynin (16 mg/kg/day) from 2 to 8 weeks after inducing diabetes mellitus (DM) with streptozotocin.ResultsDM increased excretion of hydrogen peroxide (H2O2), lipid peroxidation products (LPO), nitric oxide products (NOx), and protein. The kidneys of rats with DM had increased expression of p47phox and gp91phox and endothelial nitric oxide synthase (eNOS), and increased mesangial matrix with expression of fibronectin and collagen I. Apocynin prevented the increase in excretion of H2O2, LPO, and protein in diabetic rats, increased renal NOx generation, and prevented the increased renal expression of gp91phox and the membrane fraction of p47phox, and reverted the mesangial matrix expansion.ConclusionActivation of NADPH oxidase with translocation of p47phox to the membrane underlies the oxidative stress and limited NO generation, despite enhanced eNOS expression in a model of diabetic nephropathy. Apocynin prevents these changes and the associated proteinuria

Vibrational Modes of C_<60> Fullerene Adsorbed on Si(100)2×1 Surface Studied by High-Resolution Electron-Energy-Loss Spectroscopy

We have measured the inelastic electron-energy-loss spectra of C_ on the Si(100)2x1 surface in the infra-red energy range. If C_ is evaporated 5Å (approximately half a monolayer) on Si(100), a strong energy loss peak appears at 65 meV, and weak peaks and shoulders at 72, 144, and 175 meV. In the 12Å thick film, additional weak peaks at 96, 160, and 189 meV become more apparent. Intensities of these peaks are comparable to those of thick films measured by infra-red absorption and by Raman scattering spectroscopies. Moreover, we have measured the angle dependence of the inelastic electron intensity. These results suggest appreciable interactions between C_ and the dangling bonds of Si surface

TGF-β-dependent reprogramming of amino acid metabolism induces epithelial–mesenchymal transition in non-small cell lung cancers

Epithelial–mesenchymal transition (EMT)—a fundamental process in embryogenesis and wound healing—promotes tumor metastasis and resistance to chemotherapy. While studies have identified signaling components and transcriptional factors responsible in the TGF-β-dependent EMT, whether and how intracellular metabolism is integrated with EMT remains to be fully elucidated. Here, we showed that TGF-β induces reprogramming of intracellular amino acid metabolism, which is necessary to promote EMT in non-small cell lung cancer cells. Combined metabolome and transcriptome analysis identified prolyl 4-hydroxylase α3 (P4HA3), an enzyme implicated in cancer metabolism, to be upregulated during TGF-β stimulation. Further, knockdown of P4HA3 diminished TGF-β-dependent changes in amino acids, EMT, and tumor metastasis. Conversely, manipulation of extracellular amino acids induced EMT-like responses without TGF-β stimulation. These results suggest a previously unappreciated requirement for the reprogramming of amino acid metabolism via P4HA3 for TGF-β-dependent EMT and implicate a P4HA3 inhibitor as a potential therapeutic agent for cancer

ケツエキ トウセキ カンジャ ノ チョウキ セイメイ ヨゴ ヨソク インシ トシテノ トウセキゴ ノ ケッショウANP ト BNPノウド ノ ユウヨウセイ : 15ネンカン ノ ヨゴ チョウサ

透析患者52人において心胸比を透析前に,収縮期血圧,血清アルブミン,血漿心房性ナトリウム利尿ペプチド(atrial natriuretic peptide ; ANP),脳性ナトリウム利尿ペプチド(brain natriuretic peptide ; BNP),血漿レニン活性(plasma renin activity ; PRA),血漿ノルアドレナリン(plasma noradrenaline ; PNA)濃度を透析直後に測定した.患者は上記測定の中央値で高低2群に分けてKaplan-Meier (KM)生存曲線を求め,両群の比較をLogrank法で行った.生存期間に及ぼす因子解析は測定値を説明変数,生存期間を目的変数としてCox比例hazard法で行った.いずれもp<0.05を有意と判定した. 15年間で43人が死亡し,うち40人が病死であった. KM生存曲線は高年齢群(p<0.001),高ANP群(p=0.006),高BNP群(p=0.039)で有意に生存期間が短く,心胸比,収縮期血圧,血清アルブミン, PRA, PNAにおいては高低2群間に有意差を認めなかった. Cox比例hazard法による単変量解析では年齢(p<0.001),心胸比(p=0.011), ANP (p=0.003), BNP (p=0.002)が生命予後の有意なリスク因子となり,多変量解析ではp値は年齢<0.001,心胸比0.965, ANP 0.055, BNP 0.041となり,年齢とBNPが生命予後の独立したリスク因子であった.以上より透析患者において透析直後の血漿BNP濃度は長期生命予後の独立したリスク因子であり,血漿ANP濃度もリスク因子としてBNPに次いで重要であることが示された.This study was designed to clarify the clinical significance of post-dialysis plasma vasoactive substances including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), plasma renin activity (PRA) and noradrenaline (PNA) as a survival predictor in chronic hemo-dialysis (HD) patients. Immediately after HD, blood samples were collected for the measurements of serum albumin, ANP, BNP, PRA and PNA in 52 HD patients. During 15-year follow-up period 43 patients died ; 40 of diseases, 2 accident, 1 suicide. Patients were divided into two groups using the median of their age and clinical and laboratory variables. Kaplan-Meier survival analysis revealed that the groups of older age, higher plasma ANP and BNP concentration had significantly lower survival rates as compared with each counterpart (p<0.001, p=0.006, p=0.039, respectively). Univariate and multivariate Cox proportional hazard regression analyses were used to assess the potential association of their age, and clinical and laboratory variables with a survival rate. As a result of Univariate Cox hazard analysis, age, cardiothoracic ratio (CTR), and plasma ANP, and BNP concentrations had significant relationship with overall mortality (p<0.001, p=0.011, p=0.003, and p=0.002, respectively). However, stepwise multivariate analysis revealed that the significant relationship with overall mortality was shown for their age (p<0.001) and BNP (p=0.041). These results demonstrated that the post-dialysis plasma BNP concentration was an independent risk factor for long-term survival and the post-dialysis plasma ANP concentration was also an important risk factor next to the BNP concentration

Influence of bentonite type and producing method on hydraulic conductivity of sand–bentonite mixture

Sand-bentonite mixtures with bentonite content of 10-30% had been planned to handle low-level radioactive waste in Japan, because of its low permeability. Hydraulic conductivity of sand–bentonite mixture depends on the bentonite type, bentonite content, initial water content, and other factors. Given this background, falling head permeability tests were conducted on sand–bentonite mixture by varying the compaction energy for specimen preparation, initial water content (10–20%), and bentonite content (15– 30%). For these tests, the hydraulic gradient of 25-500 was set. Consequently, the hydraulic conductivities were 10-8 – 10-13 m/s for all tested conditions. Correlation between the hydraulic conductivity and the effective montmorillonite dry density (montmorillonite mass divided by the sum of montmorillonite, air, water volume), which is often used to correlate the hydraulic conductivity of bentonite, was found. Correlation was also found between the hydraulic conductivity and a new index designated as the effective montmorillonite wet density (sum of montmorillonite and water mass / sum of montmorillonite, air, water volume). Effective montmorillonite wet density reveals differences in the specimen structural distribution through consideration of the initial water content

Respiratory Distress Syndrome in Infants Delivered via Cesarean from Mothers with Preterm Premature Rupture of Membranes: A Propensity Score Analysis

Objective. This study aimed to clarify the effects of cesarean delivery on neonatal respiratory morbidity when women had preterm premature rupture of membranes. Methods. This retrospective study included women with preterm premature rupture of membranes who delivered from 23 weeks to 33 weeks of gestation between January 2009 and December 2014. Neonatal outcomes were compared between infants delivered by cesarean section and those delivered vaginally. The primary outcome was respiratory distress syndrome (RDS). Neonatal intubation and mechanical ventilation periods were secondary outcomes. Propensity score matching was used to compare outcomes between cesarean and vaginal delivery cases. Results. There were 101 cesarean deliveries and 89 vaginal deliveries. A comparison of the presence or absence of neonatal complications based on the delivery type indicated a higher occurrence of RDS with cesarean deliveries (P=0.025). The intubation and mechanical ventilation periods were not significantly longer in neonates delivered via cesarean section. Conclusions. Cesarean delivery is a risk factor for neonatal RDS in women with preterm premature rupture of membranes. Trials identifying long-term neonatal prognoses are needed to further develop optimal management strategies in such cases