Japanese Survey of Radiation Dose Associated With Coronary Computed Tomography Angiography　- 2013 Data From a Multicenter Registry in Daily Practice.

BACKGROUND: Although coronary computed tomography angiography (CTA) is frequently used for identifying coronary artery disease, no studies have investigated the radiation dose in detail in Japan. The aim of this study was to estimate the radiation dose of coronary CTA in Japanese clinical practice and to identify the independent predictors associated with radiation dose.Methods and Results:A multicenter, retrospective, observational study (54 institutions) was conducted for estimating the radiation dose of coronary CTA in 2,469 patients between January and December 2013. Independent predictors associated with radiation dose were investigated on linear regression analysis. Median dose-length product (DLP) was 809.0 mGy·cm (IQR, 350.0-1,368.8 mGy·cm), corresponding to an estimated radiation dose of 11 mSv. The DLP per site significantly differed between institutions (median DLP per site, 92-2,131 mGy·cm; P<0.05). Independent predictors associated with radiation dose on multivariable linear regression were body weight, heart rate, non-stable sinus rhythm, scan length, tube voltage setting, electrocardiogram (ECG)-gated scanning protocol, and the image reconstruction technique (P<0.05 each). CONCLUSIONS: The coronary CTA radiation dose was relatively high in 2013, and it varied significantly between institutions. Effective strategies for radiation dose reduction were low tube voltage ≤100 kVp, retrospective ECG-gated scanning with dose modulation technique, prospective ECG-gated scanning, and the iterative reconstruction technique.

Orexigenic action of oral zinc: metabolomic analysis in the rat hypothalamus.

We previously reported an orexigenic action of oral zinc administration in male Sprague-Dawley (SD) rats during an early stage of feeding with a zinc-deficient diet, without decreased zinc concentrations in tissues. The overall conclusion was that orally but not intraperitoneally administered zinc stimulates food intake in short-term zinc-deficient-diet fed rats. We here investigate the mechanism of the orexigenic action of zinc using GC-MS/MS-targeted metabolomic analysis in the rat hypothalamus. Four-week-old, male SD/Slc rats were used, and after 2 days of feeding with a zinc-deficient diet, 3 mg of ZnSO4 in 5 mL saline solution were administered to each rat either orally or intraperitoneally. Three hours after administration, the rats were sacrificed and the hypothalamus were excised and analyzed. We found that the oral administration group showed increased concentrations of 3-aminopropanoic acid (ß-alanine), hypotaurine, dopamine, and biotin. In light of metabolomic analysis of these results, we indicate directions for further research.

Determination of triacylglycerol oxidation mechanisms in canola oil using liquid chromatography-tandem mass spectrometry.

Triacylglycerol (TG), the main component of edible oil, is oxidized by thermal- or photo- oxidation to form TG hydroperoxide (TGOOH) as the primary oxidation product. Since TGOOH and its subsequent oxidation products cause not only the deterioration of oil quality but also various toxicities, preventing the oxidation of edible oils is essential. Therefore understanding oxidation mechanisms that cause the formation of TGOOH is necessary. Since isomeric information of lipid hydroperoxide provides insights about oil oxidation mechanisms, we focused on dioleoyl-(hydroperoxy octadecadienoyl)-TG (OO-HpODE-TG) isomers, which are the primary oxidation products of the most abundant TG molecular species (dioleoyl-linoleoyl-TG) in canola oil. To secure highly selective and sensitive analysis, authentic OO-HpODE-TG isomer references (i.e., hydroperoxide positional/geometrical isomers) were synthesized and analyzed with HPLC-MS/MS. With the use of the method, photo- or thermal- oxidized edible oils were analyzed. While dioleoyl-(10-hydroperoxy-8E,12Z-octadecadienoyl)-TG (OO-(10-HpODE)-TG) and dioleoyl-(12-hydroperoxy-9Z,13E-octadecadienoyl)-TG (OO-(12-HpODE)-TG) were characteristically detected in photo-oxidized oils, dioleoyl-(9-hydroperoxy-10E,12E-octadecadienoyl)-TG and dioleoyl-(13-hydroperoxy-9E,11E-octadecadienoyl)-TG were found to increase depending on temperature in thermal-oxidized oils. These results prove that our methods not only evaluate oil oxidation in levels that are unquantifiable with peroxide value, but also allows for the determination of oil oxidation mechanisms. From the analysis of marketed canola oils, photo-oxidized products (i.e., OO-(10-HpODE)-TG and OO-(12-HpODE)-TG) were characteristically accumulated compared to the oil analyzed immediately after production. The method described in this paper is valuable in the understanding of oil and food oxidation mechanisms, and may be applied to the development of preventive methods against food deterioration.

HPLC-MS/MS: A potential method to track the in vivo degradation of zein-based biomaterial.

Given the inadequacies of existing clinic tracking strategies, such as isotopic tracer techniques, one of the major thrusts in protein-based tissue engineering substitutes prior to use in clinic is to develop a safe technique that can effectively track their degradation in vivo. Keeping in view the possible application of a natural polymer, zein as a novel bone substitute, with the advantages of good bio-compatibility, bio-degradability and outstanding mechanical properties, we attempted here to construct a HPLC-MS/MS method to track the in vivo degradation of zein porous scaffold. Histological observation and immunohistochemistry analysis using the intramuscular implantation model of rats clearly indicated that zein porous scaffold has certain osteoinductive ability. More importantly, HPLC-MS/MS detected the changes of amino acids levels in plasma and different organs after the implantation of scaffolds. With these findings, it could be concluded that HPLC-MS/MS might be a potential method to track the in vivo degradation of protein-based tissue engineering substitutes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 606-613, 2018.

Determinants of polyunsaturated fatty acid concentrations in erythrocytes of pregnant Japanese women from a birth cohort study: study protocol and baseline findings of an adjunct study of the Japan environment & Children's study.

BACKGROUND: N-3 polyunsaturated fatty acids (n-3 PUFA) may have multiple beneficial effects on the outcome of pregnancy, maternal health and child development. The present study introduced the protocol of a birth cohort study to examine the beneficial effects of n-3 PUFA status in pregnant Japanese women as an adjunct study of the Japan Environment and Children's Study (JECS). METHODS: The JECS participants in the coastal areas of Miyagi Prefecture were further invited to participate in this adjunct study, and 1,878 pregnant women were enrolled prior to delivery. Their n-3 PUFA status was evaluated with fatty acid profiles in erythrocytes of maternal blood collected from 1,623 mothers at 24-30 weeks of gestation and cord blood from 1,505 deliveries. RESULTS: The baseline results, including comprehensive data on the fatty acid status and determinants affecting the PUFA status, were analyzed. In stepwise multivariate analyses, the cord blood docosahexaenoic acid (DHA) level was found to be significantly influenced by the DHA level in maternal blood, the child's sex, and the gestational period. The maternal DHA level was influenced by fish intake, maternal age, and the prepregnancy body mass index. While cord blood eicosapentaenoic acid (EPA) was influenced by maternal EPA, fish intake, and season at birth, additional factors such as maternal education, household income, and smoking habits affected the maternal EPA content. CONCLUSION: Further studies are warranted to clarify the nutritional impacts of n-3 PUFA in pregnant Japanese women of the cohort study.

Radiologic-Pathologic Correlation of Primary and Secondary Cardiomyopathies: MR Imaging and Histopathologic Findings in Hearts from Autopsy and Transplantation.

Cardiac magnetic resonance (MR) imaging with late gadolinium enhancement (LGE) is used to detect and assess the myocardial damage seen with a variety of cardiomyopathies. Gadolinium-based contrast material accumulates in the expanded interstitial space of the myocardium. Areas with LGE correspond to replacement fibrosis, fibrofatty change, epithelioid granuloma, inflammatory cell infiltration, cardiomyocyte necrosis, and amyloid deposition-conditions that represent a focal increase in interstitial space. Areas without LGE correspond to interstitial or plexiform fibrosis, mildly degenerated cardiomyocytes, inflammatory cell infiltration, and diffuse amyloid deposition-conditions that represent diffuse increases in interstitial space. LGE MR imaging cannot depict these diffuse changes and does not enable quantitative evaluation of this increased interstitial space because on inversion-recovery MR images, the inversion time is adjusted to null the signal from normal-appearing or the least enhancing regions of the myocardium. Thus, the absence of LGE does not always indicate normal myocardial tissue. The use of current T1 mapping techniques enables one to overcome these drawbacks of LGE imaging, detect diffuse myocardial abnormalities, and perform quantitative analysis of the interstitial space. The authors describe the histopathologic and corresponding cardiac MR imaging findings of hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, cardiac sarcoidosis, giant cell myocarditis, and cardiac amyloidosis-mainly those seen on LGE MR images-as assessed by using whole-heart specimens obtained from autopsy or transplantation. ©RSNA, 2017.

Diagnostic features of cardiac cavernous hemangioma in the right ventricle on magnetic resonance imaging.

Cardiac tumors are rare; however, with recent advances in imaging techniques, they are being diagnosed more frequently with cardiac magnetic resonance (CMR) imaging. We report a case of a cardiac cavernous hemangioma in the right ventricle. This case was diagnosed with CMR imaging based on the characteristic features of peripheral nodular contrast enhancement and progressive centripetal fill-in. CMR imaging also provided useful preoperative anatomical information, showing the relationships among the tumor, tricuspid valve, and right ventricular anterior wall.

Lipoprotein profiles of hepatic cell lines at various stages of differentiation.

We studied the lipoprotein profiles of human hepatic cells at various stages of differentiation. The production of three major classes of lipoproteins, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), was detected in three well-differentiated human hepatoma cell lines and primary human hepatocytes; however, these lipoproteins were not detected in the culture medium in which undifferentiated hepatoma cell lines were grown. Reverse transcription polymerase chain reaction analysis demonstrated that the expression levels of apolipoprotein A1 (ApoA1), ApoB100, and microsomal triglyceride transfer protein (MTP) were markedly lower in the undifferentiated hepatoma cell lines than in the well-differentiated hepatoma cell lines and primary hepatocytes. These results indicate that apolipoprotein synthesis, and triglyceride-transport by MTP might be rate-limiting steps in lipoprotein production in mature hepatic cells.

δ and γ tocotrienols suppress human hepatocellular carcinoma cell proliferation via regulation of Ras-Raf-MEK-ERK pathway-associated upstream signaling.

Tocotrienol (T3) has recently gained increasing interest due to its anti-cancer effect. Here, we investigated the modulating effect of δ and γ T3 on the Ras-Raf-MEK-ERK oncogenic upstream signaling pathway in human hepatocellular carcinoma HepG2 cells. The results indicated that T3 regulated the upstream signaling cascades of this pathway.

Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration.

PURPOSE: Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. METHODS: Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. RESULTS: Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. CONCLUSION: These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future studies should focus on enhancing the resistance to metabolic degradation and conversion of CUR to other metabolites, which may lead to novel discoveries regarding food function and disease prevention.

Metabolic Fate of Luteolin in Rats: Its Relationship to Anti-inflammatory Effect.

Luteolin is a naturally occurring flavone that reportedly has anti-inflammatory effects. Because most luteolin is conjugated following intestinal absorption, free luteolin is likely present at low levels in the body. Therefore, luteolin metabolites are presumably responsible for luteolin bioactivity. Here we confirmed that luteolin glucuronides, especially luteolin-3'-O-glucuronide, are the major metabolites found in plasma after oral administration of luteolin (aglycone) or luteolin glucoside (luteolin-7-O-glucoside) to rats. Luteolin-4'-O-glucuronide and luteolin-7-O-glucuronide were also detectable together with luteolin-3'-O-glucuronide in the liver, kidney, and small intestine. Next, we prepared these luteolin glucuronides and compared the anti-inflammatory effects of luteolin and luteolin glucuronides on gene expression in lipopolysaccharide-treated RAW264.7 cells. Luteolin glucuronides, especially luteolin-7-O-glucuronide, reduced expression of inflammatory genes in the cells, although their effects were weaker than those of luteolin. These results indicate that the active compound responsible for the anti-inflammatory effect of luteolin in vivo would be luteolin glucuronide and/or residual luteolin.

Cardiac magnetic resonance imaging-based myocardial strain study for evaluation of cardiotoxicity in breast cancer patients treated with trastuzumab: A pilot study to evaluate the feasibility of the method.

BACKGROUND: Trastuzumab, used to treat breast cancer overexpressing human epidermal growth factor receptor 2, may be cardiotoxic. Cardiac magnetic resonance (CMR) imaging with myocardial strain studies has been used to evaluate subclinical biventricular myocardial changes, however, its clinical utility during chemotherapy has not been evaluated. METHODS: The clinical outcomes, CMR and cardiac biomarkers of 9 women aged 62.3 ± 12.6 years with early or locally advanced breast cancer were evaluated at baseline, and at 3, 6 and 12 months after the initiation of trastuzumab. RESULTS: None of the patients developed heart failure or elevated serum cardiac biomarkers. Global left ventricular (LV) peak systolic longitudinal and circumferential strains were significantly decreased at 6 months (longitudinal strains, -21.1 ± 1.7% [baseline] vs. -19.5 ± 1.0% [6 months], p = 0.039, and circumferential strains, -23.4 ± 1.8% [baseline] vs. -21.6 ± 2.5% [6 months], p = 0.036). These changes were analogous to those observed in the LV ejection fraction. Right ventricular (RV) free wall peak systolic circumferential strains were decreased at 6 months (-20.9% ± 2.4% [baseline] vs. -19.1% ± 2.3% [6 months], p = 0.049), whereas RV longitudinal strains and ejection fraction remained unchanged. The LV longitudinal strain was the most reproducible of the 4 peak strain parameters. CONCLUSIONS: The LV longitudinal and circumferential strains measured by CMR decreased during trastuzumab therapy, although their predictive value for later heart failure or association with RV parameters was not determined. These techniques may be a useful means of diagnosing and monitoring trastuzumab-related cardiotoxicity.

CT Features of Epidermal Growth Factor Receptor-Mutated Adenocarcinoma of the Lung: Comparison with Nonmutated Adenocarcinoma.

INTRODUCTION: The purpose of this study was to analyze the high-resolution computed tomography (HRCT) features of lung carcinoma on the basis of epidermal growth factor receptor gene (EGFR) mutation status. METHODS: A total of 263 consecutive patients in whom lung adenocarcinoma was diagnosed at our institution between January 2010 and December 2011 were enrolled in the study. All patients underwent HRCT and analysis of EGFR mutation status. The HRCT findings were retrospectively analyzed for tumor size, multiple bilateral lung metastases, convergence of surrounding structures, surrounding ground-glass opacity, prominent peribronchovascular extension, air bronchogram, notch, pleural indentation, spiculation, cavity, and pleural effusions. RESULTS: EGFR mutations were demonstrated in 103 patients (39.2%); the remaining 160 patients (60.8%) had the nonmutated type of adenocarcinoma. Compared with the nonmutated group, the mutated group had significantly higher frequencies of multiple bilateral lung metastases (p = 0.0152), convergence of surrounding structures (p < 0.0001), ground-glass opacity (p = 0.0011), and notch (p = 0.0428), but significantly lower frequencies of cavitation (p = 0.0004) and pleural effusions (p = 0.0064). The frequencies of the other CT findings were similar between the two groups. The devised prediction HRCT score for EGFR mutation was 78.4% sensitive and 70.4% specific. CONCLUSIONS: EGFR-mutated adenocarcinoma showed significantly higher frequencies of multiple bilateral lung metastases, convergence of surrounding structures, surrounding ground glass opacity, and notch at HRCT compared with the non-EGFR-mutated type. Conversely, EGFR-mutated adenocarcinoma showed cavity and pleural effusions less frequently than the nonmutated type did.

Intraspinal collateral circulation to the artery of Adamkiewicz detected with intra-arterial injected computed tomographic angiography.

When the intercostal and lumbar arteries are occluded by plaque or thrombus, spinal cord perfusion depends on collateral circulation. Some reports have demonstrated collateral circulation to the artery of Adamkiewicz via computed tomography and magnetic resonance angiographies. However, intraspinal collateral circulation to the artery of Adamkiewicz along the spinal cord has not been reported previously. Here, we report two patients with intraspinal collateral circulation to the artery of Adamkiewicz along the spinal cord that was detected with intra-arterial injected computed tomography angiography.

Carbon tetrachloride-induced hepatic and renal damages in rat: inhibitory effects of cacao polyphenol.

Here, we investigated the protective effect of cacao polyphenol extract (CPE) on carbon tetrachloride (CCl4)-induced hepato-renal oxidative stress in rats. Rats were administered CPE for 7 days and then received intraperitoneal injection of CCl4. Two hours after injection, we found that CCl4 treatment significantly increased biochemical injury markers, lipid peroxides (phosphatidylcholine hydroperoxide (PCOOH) and malondialdehyde (MDA)) and decreased glutathione peroxidase activity in kidney rather than liver, suggesting that kidney is more vulnerable to oxidative stress under the present experimental conditions. CPE supplementation significantly reduced these changes, indicating that this compound has antioxidant properties against CCl4-induced oxidative stress. An inhibitory effect of CPE on CCl4-induced CYP2E1 mRNA degradation may provide an explanation for CPE antioxidant property. Together, these results provide quantitative evidence of the in vivo antioxidant properties of CPE, especially in terms of PCOOH and MDA levels in the kidneys of CCl4-treated rats.

Diffusion-weighted MR imaging findings of ovarian adenocarcinofibromas and adenofibromas.

We retrospectively evaluated pelvic magnetic resonance imaging including diffusion-weighted imaging (DWI) of 16 ovarian lesions (5 adenocarcinofibromas, 2 borderline adenofibromas, and 9 benign adenofibromas). All adenocarcinofibromas were detected as large solid areas of strong high signal on DWI, and seven of nine benign adenofibromas and both borderline adenofibromas demonstrated no areas of high signal or small areas of weak high signal. Solid components that appear as areas of strong high signal on DWI might represent a characteristic finding of adenocarcinofibromas.

Comparison of the effects of curcumin and curcumin glucuronide in human hepatocellular carcinoma HepG2 cells.

Curcumin is a yellow pigment found in turmeric (Curcuma Longa L.), and is reported, in recent studies, to have several pharmacological effects, including anti-oxidant, anti-inflammatory, anti-tumour and lipid-lowering properties. However, as most curcumin is conjugated when absorbed through the intestine, free curcumin is present at extremely low levels inside the body. Therefore, curcumin metabolites have been presumed to be responsible for the curcumin bioactivity. In this study, we first confirmed that curcumin glucuronide is the major metabolite of curcumin found in the plasma after oral administration of curcumin in rats. Next, we synthesised curcumin glucuronide and compared the effects of curcumin and curcumin glucuronide on gene expression in a human hepatoma cell line (HepG2). We found that the effects of curcumin glucuronide are weaker than those of curcumin and that this difference is related to relative absorption rates of curcumin and curcumin glucuronide into HepG2 cells.

Utility of ECG-gated MDCT to differentiate patients with ARVC/D from patients with ventricular tachyarrhythmias.

BACKGROUND: The accuracy of electrocardiogram-gated CT for diagnosing arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is uncertain. OBJECTIVE: We propose a comprehensive system for scoring characteristic CT findings to diagnose ARVC/D and discuss its utility. METHODS: Seventy-seven patients (mean age, 43.1 years; 48 male) diagnosed with ARVC/D or with suspected ARVC/D on the basis of ventricular tachyarrhythmias underwent CT with and without contrast enhancement. We retrospectively graded characteristic CT findings (fatty tissue, bulging appearance, and dilatation of the right ventricle) as minor (1 point) or major (2 points) and then validated our scoring system's utility for diagnosing ARVC/D with the use of the modified 2010 Task Force criteria as the reference standard. RESULTS: We diagnosed 27 of 77 patients with ARVC/D (23 definite, 4 borderline), observing each CT finding more often in patients with ARVC/D than in patients without ARVC/D: fatty tissue, 74.1% versus 12.0%; bulging appearance, 74.1% versus 34.0%; and RV dilatation, 92.6% versus 44.0%. However, observation of each finding in both groups could cause false positive diagnosis. Recursive partitioning analysis showed the superiority of our CT scoring system over methods that used each CT finding and CT findings without fatty tissue for distinguishing ARVC/D and non-ARVC/D. For overall (definite and borderline) and definite ARVC/D diagnosis, sensitivities were 77.8% and 87.0%, specificities were 96.0% and 94.4%, positive predictive values were 91.3% and 87.0%, negative predictive values were 88.9% and 94.4%, and accuracies were 89.6% and 92.2%, respectively. CONCLUSIONS: Our CT scoring system showed excellent diagnostic ability and might aid differentiation of ARVC/D from ventricular tachyarrhythmias.