Prevention of contrast-induced nephropathy by chronic pravastatin treatment in patients with cardiovascular disease and renal insufficiency

SummaryBackgroundContrast-induced nephropathy (CIN) is known to increase morbidity and mortality of cardiovascular disease. Recent studies have shown statins prevented CIN after contrast media exposure, but optimal statin type and dosage are still unknown.PurposeThe aims of the present study were to evaluate whether chronic pravastatin treatment before scheduled coronary angiography or percutaneous coronary intervention could reduce the incidence of CIN and to elucidate the factors related to CIN in patients with renal insufficiency.MethodsWe studied 431 consecutive patients with renal insufficiency. One hundred ninety-four patients were receiving pravastatin treatment as standard chronic treatment of hypercholesterolemia. Serum creatinine levels were measured at baseline (pre-procedure) and within 48h after contrast media exposure (peak post-procedure). CIN was defined as an increase in the serum creatinine values of ≥25% or ≥0.5mg/dl after contrast media exposure. Logistic regression analysis was performed to evaluate the important factors related to CIN using four variables: age, pravastatin, pre-procedure serum creatinine, and contrast volume.ResultsCIN was observed in 36 patients (8.4%). Patients without pravastatin (p<0.01), high level pre-procedure serum creatinine (p<0.01), and high contrast volume (p=0.034) had a significantly higher incidence of CIN. Logistic regression analysis revealed that pravastatin treatment (χ2=6.549, p=0.011, odds ratio=0.34), pre-procedure serum creatinine (χ2=6.294, p=0.009, odds ratio=2.78), and contrast volume (χ2=4.484, p=0.034, odds ratio=1.01) were independently related to the decreased risk of CIN.ConclusionsChronic pravastatin treatment before contrast media exposure was important for preventing CIN in patients with renal insufficiency. Also, reducing the dose of contrast media was important for preventing CIN in patients with high-baseline serum creatinine levels

Giant Anomalous Hall Conductivity at the Pt/Cr₂O₃ Interface

The interface between a magnetic material and a heavy metal that has a large spin-orbit interaction is at the root of various spin-related phenomena. In this paper, we address the peculiar spin-dependent transport at a Pt/Cr₂O₃ interface by exploring the origin of the nonlinear anomalous Hall effect (AHE) in Pt/Cr₂O₃ bilayers. X-ray magnetic circular dichroism (XMCD) measurements show no appreciable magnetic moment at the interface originating from Cr 3d and Pt 5d orbitals, which could be associated with the AHE response. A possible interfacial magnetic moment M at the Pt/Cr₂O₃ interface, assumed from the detection limit of the XMCD measurements, yields an anomalous Hall conductivity (σAHE) per unit net magnetic moment (M),-σAHE/M, of 0.57 V-1, which is extraordinary large compared with that for general magnetic materials. Together with first-principles calculations, the results suggest the possibility of an intrinsic AHE in the Pt/Cr₂O₃ interface that does not rely on the net magnetic moment.T.Moriyama, Y.Shiratsuchi, T.Iino, et al. Giant Anomalous Hall Conductivity at the Pt/Cr₂O₃ Interface. Physical Review Applied 13, 034052 (2020); https://doi.org/10.1103/PhysRevApplied.13.034052

Simultaneous achievement of high perpendicular exchange bias and low coercivity by controlling ferromagnetic/antiferromagnetic interfacial magnetic anisotropy

This study investigates the influence of Pt and Au spacer layers on the perpendicular exchange bias field and coercivity of Pt/Co/(Pt or Au)/Cr₂O₃/Pt films. When using a Pt-spacer, the perpendicular exchange bias was highly degraded to less than 0.1 erg/cm², which was about half that of the Au-spacer system. The Au spacer also suppressed the enhancement in coercivity that usually occurs at around room temperature when using Pt. It is suggested that this difference in exchange bias field is due to in-plane interfacial magnetic anisotropy at the Pt/Cr₂O₃ interface, which cants the interfacial Cr spin from the surface normal and results in degradation in the perpendicular exchange bias.Yu Shiratsuchi, Wataru Kuroda, Thi Van Anh Nguyen, Yoshinori Kotani, Kentaro Toyoki, Tetsuya Nakamura, Motohiro Suzuki, Kohji Nakamura, and Ryoichi Nakatani, Journal of Applied Physics 121, 073902 (2017); https://doi.org/10.1063/1.4976568

TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Currently definitive 5-fluorouracil (5-FU)/cisplatin (CDDP) -based chemotherapy is recognized as one of the most promising treatments for esophageal cancer. A series of studies performed found genetic polymorphisms and the plasma concentration of 5-FU to be predictive of acute severe toxicities and clinical response. Genetic polymorphisms of <it>tumor necrosis factor (TNF) -α </it>and its surface receptors, <it>TNFRSF1A </it>and <it>TNFRSF1B </it>have been examined in terms of susceptibility to various cancers. In this study, genetic polymorphisms of <it>TNFRSF1B </it>gene were evaluated Japanese esophageal squamous cell carcinoma (ESCC) patients treated with the definitive 5-FU/CDDP-based chemoradiotherapy and their predictive values of prognosis or severe acute toxicities were assessed.</p> <p>Methods</p> <p>Forty-six patients with ESCC were treated with the definitive 5-FU/CDDP-based chemoradiotherapy, one course of which consisted of the continuous infusion of 5-FU for days 1-5 and 8-12, the infusion of CDDP on days 1 and 8, and the radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course repeated after 2-week interval. Genetic polymorphisms of a TNF-α receptor <it>TNFRSF1B </it>gene were determined by a TaqMan^®MGB probe-based polymerase chain reaction.</p> <p>Results</p> <p>The genotype of <it>TNFSR1B </it>A1466G, but not M196R/T587G or C1493T, was found to be predictive of clinical response, i.e., a complete response or not (p = 0.040). Clinical response was predicted by tumor size (p = 0,002), lymph node metastasis (p = 0.007), distant metastasis (p = 0.001) and disease stage (p < 0.001), but <it>TNFRSF1B </it>A1466G genotype was independent of these factors.</p> <p>Conclusions</p> <p>Genetic polymorphism of <it>TNFRSF1B </it>A1466G was found to be predictive response in Japanese ESCC patients with a definitive 5-FU/CDDP-based chemoradiotherapy. Further clinical investigation with a large number of patients or experiments in vitro should be performed to assess the predictive value of <it>TNFRSF1B </it>A1466G genotype after chemoradiotherapy.</p

Microscale flow dynamics of red blood cells in a circular microchannel

The blood flow dynamics in microcirculation depends strongly on the motion, deformation and interaction of RBCs within the microvessel. This paper presents the application of a confocal micro-PTV system to track RBCs through a circular polydimethysiloxane (PDMS) microchannel. This technique, consists of a spinning disk confocal microscope, high speed camera and a diode-pumped solid state (DPSS) laser combined with a single particle tracking (SPT) method. By using this system detailed motions of individual RBCs were measured at a microscale level. Our results showed that this technique can provide detailed information about microscale disturbance effects caused by RBCs in flowing blood

Effects of plasma concentrations of 5-fluorouracil on long-term survival after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>A substantial body of literature has accumulated during the past 20 years showing the plasma concentrations of 5-fluorouracil (5-FU) to correlate with clinical response and/or toxicity in colorectal cancer, and head and neck cancer, but little information is available concerning effects on long-term survival. Here, Japanese patients with esophageal squamous cell carcinoma (ESCC) were followed up for 5 years after treatment with a definitive 5-FU/cisplatin (CDDP)-based chemoradiotherapy (CRT), and the association between prognosis and the plasma concentration of 5-FU was evaluated.</p> <p>Methods</p> <p>Forty-nine patients with ESCC, who were treated with a definitive 5-FU/CDDP-based CRT, were enrolled. A course consisted of the continuous infusion of 5-FU at 400 mg/m²/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m²/day on days 1 and 8, and the radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. Plasma concentrations of 5-FU were determined by high performance liquid chromatography at 5:00 PM on days 3, 10, 38 and 45, and at 5:00 AM on days 4, 11, 39 and 46.</p> <p>Results</p> <p>The overall 5-year survival rate was 42.9%. Age (P = 0.020), body weight (P = 0.019), and disease stage (P = 0.048) affected the survival, and the survival depended on the clinical response assessed at 1 month after the treatment (P = 0.001). Higher plasma concentrations of 5-FU resulted in a better clinical response (P = 0.043), and trended to prolong survival (P = 0.321).</p> <p>Conclusions</p> <p>The long-term survival after treatment with a definitive 5-FU/CDDP-based CRT possibly depends on the plasma concentrations of 5-FU, and further clinical studies with a larger number of cases are needed to clarify the relationship between them.</p

Coactosin Promotes F-Actin Protrusion in Growth Cones Under Cofilin-Related Signaling Pathway

During brain development, axon outgrowth and its subsequent pathfinding are reliant on a highly motile growth cone located at the tip of the axon. Actin polymerization that is regulated by actin-depolymerizing factors homology (ADF-H) domain-containing family drives the formation of lamellipodia and filopodia at the leading edge of growth cones for axon guidance. However, the precise localization and function of ADF-H domain-containing proteins involved in axon extension and retraction remain unclear. We have previously shown that transcripts and proteins of coactosin-like protein 1 (COTL1), an ADF-H domain-containing protein, are observed in neurites and axons in chick embryos. Coactosin overexpression analysis revealed that this protein was localized to axonal growth cones and involved in axon extension in the midbrain. We further examined the specific distribution of coactosin and cofilin within the growth cone using superresolution microscopy, structured illumination microscopy, which overcomes the optical diffraction limitation and is suitable to the analysis of cellular dynamic movements. We found that coactosin was tightly associated with F-actin bundles at the growth cones and that coactosin overexpression promoted the expansion of lamellipodia and extension of growth cones. Coactosin knockdown in oculomotor neurons resulted in an increase in the levels of the inactive, phosphorylated form of cofilin and dysregulation of actin polymerization and axonal elongation, which suggests that coactosin promoted axonal growth in a cofilin-dependent manner. Indeed, the application of a dominant-negative form of LIMK1, a downstream effector of GTPases, reversed the effect of coactosin knockdown on axonal growth by enhancing cofilin activity. Combined, our results indicate that coactosin functions promote the assembly of protrusive actin filament arrays at the leading edge for growth cone motility