Structural and infrared spectral changes of silicon oxide grains by heat treatments

In order to elucidate the relationship between crystallographic structures of amorphous silicon oxide grains and infrared (IR) spectra, ultrafine grains produced by the gas evaporation method have been studied on the basis of IR spectral measurements and electron microscopic (EM) observations. The shifts and disappearance in the IR absorption peaks of specimen heat-treated in air have been found. The spectral changes have been discussed in the relation with the polymorphism of silica

Significance of Exercise-Related Ventricular Arrhythmias in Patients With Brugada Syndrome

Background Sinus tachycardia during exercise attenuates ST‐segment elevation in patients with Brugada syndrome, whereas ST‐segment augmentation after an exercise test is a high‐risk sign. Some patients have premature ventricular contractions (PVCs) related to exercise, but the significance of exercise‐related PVCs in patients with Brugada syndrome is still unknown. The objective of this study was to determine the significance of exercise‐related PVCs for predicting occurrence of ventricular fibrillation (VF) in patients with Brugada syndrome. Methods and Results The subjects were 307 patients with Brugada syndrome who performed a treadmill exercise test. We evaluated the occurrence of PVCs at rest, during exercise and at the peak of exercise, and during recovery after exercise (0–5 minutes). We followed the patients for 92±68 months and evaluated the occurrence of VF. PVCs occurred in 82 patients (27%) at the time of treadmill exercise test: PVCs appeared at rest in 14 patients (4%), during exercise in 60 patients (20%), immediately after exercise (0–1.5 minutes) in 28 patients (9%), early after exercise (1.5–3 minutes) in 18 patients (6%), and late after exercise (3–5 minutes) in 12 patients (4%). Thirty patients experienced VF during follow‐up. Multivariable analysis including symptoms, spontaneous type 1 ECG, and PVCs in the early recovery phase showed that these factors were independently associated with VF events during follow‐up. Conclusions PVCs early after an exercise test are associated with future occurrence of VF events. Rebound of vagal nerve activity at the early recovery phase would promote ST‐segment augmentation and PVCs in high‐risk patients with Brugada syndrome

Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet

Background Statins suppress the progression of atherosclerosis by reducing low-density lipoprotein (LDL) cholesterol levels. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor alpha modulator, is expected to reduce residual risk factors including high triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol during statin treatment. However, it is not known if statin therapy with add-on pemafibrate improves the progression of atherosclerosis. The aim of this study was to assess the effect of combination therapy with pitavastatin and pemafibrate on lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Methods Seven-week-old male Dahl salt-sensitive (DS) rats were divided into the following five treatment groups (normal diet (ND) plus vehicle, high-salt and high-fat diet (HD) plus vehicle, HD plus pitavastatin (0.3 mg/kg/day), HD plus pemafibrate (K-877) (0.5 mg/kg/day), and HD plus combination of pitavastatin and pemafibrate) and treated for 12 weeks. At 19 weeks, endothelium-dependent relaxation of the thoracic aorta in response to acetylcholine was evaluated. Results After feeding for 12 weeks, systolic blood pressure and plasma levels of total cholesterol were significantly higher in the HD-vehicle group compared with the ND-vehicle group. Combination therapy with pitavastatin and pemafibrate significantly reduced systolic blood pressure, TG levels, including total, chylomicron (CM), very LDL (VLDL), HDL-TG, and cholesterol levels, including total, CM, VLDL, and LDL-cholesterol, compared with vehicle treatment. Acetylcholine caused concentration-dependent relaxation of thoracic aorta rings that were pre-contracted with phenylephrine in all rats. Relaxation rates in the HD-vehicle group were significantly lower compared with the ND-vehicle group. Relaxation rates in the HD-combination of pitavastatin and pemafibrate group significantly increased compared with the HD-vehicle group, although neither medication alone ameliorated relaxation rates significantly. Western blotting experiments showed increased phosphorylated endothelial nitric oxide synthase protein expression in aortas from rats in the HD-pemafibrate group and the HD-combination group compared with the HD-vehicle group. However, the expression levels did not respond significantly to pitavastatin alone. Conclusions Combination therapy with pitavastatin and pemafibrate improved lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Pemafibrate as an add-on strategy to statins may be useful for preventing atherosclerosis progression

Primary leiomyoma of the bladder

The case presented is of a 47-year-old patient with an extravesical pedunculated bladder leiomyoma, which was difficult to distinguish from a retroperitoneal tumor. Preoperatively, it was suspected to be a retroperitoneal tumor and a laparotomy with tumor resection was performed. lntraoperatively, the bladder and tumor were connected by a cord-like tissue. A retrospective review of preoperative images revealed that cord-like tissue, identified intraoperatively, was also present. Bladder leiomyomas can grow as extravesical pedunculated tumors. Therefore, when the continuity between the bladder and tumor is only a cord-like object, the finding of continuity is useful to diagnose with bladder leiomyoma

MRP3 as a novel resistance factor for sorafenib in hepatocellular carcinoma

The mechanism of resistance of hepatocellular carcinoma (HCC) to sorafenib is unknown and no useful predictive biomarker for sorafenib treatment has been reported. Accordingly, we established sorafenib-resistant HCC cells and investigated the underlying mechanism of resistance to sorafenib. Sorafenib-resistant cell lines were established from the HCC cell line PLC/PRF5 by cultivation under continuous exposure to increasing concentration of sorafenib. The IC50 values of the 2 resistant clones PLC/PRF5-R1 and PLC-PRF5-R2 were 9.2±0.47 μM (1.8-fold) and 25±5.1 μM (4.6-fold) respectively, which were significantly higher than that of parental PLC/PRF5 cells (5.4±0.17 μM) (p<0.01 respectively), as determined by MTT assay. Western blot analysis of signal transduction-related proteins showed no significant differences in expression of AKT/pAKT, mTOR/pmTOR, or ERK/pERK between the 2 resistant clones versus parent cells, suggesting no activation of an alternative signal transduction pathway. Likewise, when expression of membrane transporter proteins was determined, there were no significant differences in expression levels of BSEP, MDR1, MRP2, BCRP, MRP4 and OCT1 between resistant clones and parent cells. However, the expression levels of MRP3 in the 2 resistant clones were significantly higher than that of parent cells. When MRP3 gene was knocked down by siRNA in PLC-PRF5-R2 cells, the sensitivity of the cells to sorafenib was restored. In the analysis of gene mutation, there was no mutation in the activation segment of Raf1 kinase in the resistant clones. Our data clearly demonstrate that the efflux transporter MRP3 plays an important role in resistance to sorafenib in HCC cells

APOBコドン4311遺伝子多型は脂質代謝を変化させることによりC型肝炎ウイルスの感染性に関与する

Background: It has been reported that some single-nucleotide polymorphisms (SNPs) in lipid regulators such as apolipoproteins and cell surface molecules for hepatitis C virus (HCV) entry into hepatocytes are associated with HCV infection. However, it is unknown how HCV infection is affected by altered lipid metabolism resulting from the SNPs. We investigated the relationship between these SNPs and HCV infection status, and also analyzed the mechanism by which these SNPs mediate HCV infection via lipid metabolism alterations. Methods: Serum lipid and apolipoprotein profiles were tested in 158 HCV-positive and 220 HCV-negative subjects. We selected 22 SNPs in five lipid regulator genes which were related to HCV entry into hepatocytes and to lipid metabolism (APOA1, APOB, SR-B1, LDLR, and APOE), and their polymorphisms were analyzed using the PCR-sequencespecific oligonucleotide probe-Luminex method. Results: An APOB N4311S (g.41553a > g) SNP, rs1042034, was significantly associated with HCV positivity; the HCV positivity rate for the minor allele AA genotype was significantly higher than for genotype AG + GG (P = 0.016). Other SNPs except for APOB P2712L SNP rs676210, which is in linkage disequilibrium with rs1042034, showed no significant difference in genotype distribution. The serum level of low density lipoprotein-cholesterol (LDL-C) in the genotype AA group was significantly lower than in the genotype non-AA group (P = 0.032), whereas the triglyceride (TG) level was significantly higher (P = 0.007). Conclusion: An APOB SNP, rs1042034, is closely associated with HCV infection through lipid metabolism alteration. The minor allele AA genotype might contribute to facilitating serum LDL uptake into hepatocytes via LDLR by modifying their affinity and interaction and may have an influence on HCV infection by their entry to the liver through the LDLR