Size and Surface Properties of Functionalized Organosilica Particles Impact Cell-Particle Interactions Including Mitochondrial Activity.

Understanding of the interactions between macrophages and multifunctional nanoparticles is important for development of novel macrophage-based immunotherapies. Here, we investigated the effects of fluorescent thiol-organosilica particle size and surface properties on cell-particle interactions, including mitochondrial activity, using the mouse macrophage cell line J774A.1. Three different sizes of thiol-organosilica particles (150, 400, and 680 nm in diameter) containing fluorescein (OS/F150, OS/F400, and OS/F680) and particles surface functionalized with polyethylenimine (PEI) (OS/F150PEI, OS/F400PEI, and OS/F680PEI) were prepared. Flow cytometric analysis, time-lapse imaging, and single-cell analysis of particle uptake and mitochondrial activity of J774A.1 cells demonstrated variations in uptake and kinetics depending on the particle size and surface as well as on each individual cell. Cells treated with OS/F150 and OS/F150PEI showed higher uptake and mitochondrial activity than those treated with other particles. The interaction between endosomes and mitochondria was observed using 3D fluorescent imaging and was characterized by the involvement of iron transport into mitochondria by iron-containing proteins adsorbed on the particle surface. Scanning electron microscopy of the cells treated with the particles revealed alterations in cell membrane morphology, depending on particle size and surface. We performed correlative light and electron microscopy combined with time-lapse and 3D imaging to develop an integrated correlation analysis of particle uptake, mitochondrial activity, and cell membrane morphology in single macrophages. These cell-specific characteristics of macrophages against functional particles and their evaluation methods are crucial for understanding the immunological functions of individual macrophages and developing novel immunotherapies.

The effect of Dunaliella tertiolecta supplementation on diet-induced obesity in UCP1-deficient mice.

We previously demonstrated that dietary supplementation with Dunaliella tertiolecta (DT) increases uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) and improves diet-induced obesity (DIO) in C57BL/6 J mice at thermoneutrality (30 °C). Here, we investigated whether DT improves DIO in a thermoneutral UCP1-deficient (KO) animal. KO mice were fed a high-fat diet supplemented with DT for 12 weeks. Compared to control group without DT, body weight was significantly reduced in DT group with no difference in food intake. Dunaliella tertiolecta-supplemented mice exhibited lower adiposity and well-maintained multilocular morphology in BAT, in which a significant increase in gene expression of PR domain containing 16 was detected in DT group compared to control group. Moreover, increase in UCP2 level and/or decrease in ribosomal protein S6 phosphorylation were detected in adipose tissues of DT group relative to control group. These results suggest that DT supplementation improves DIO by stimulating UCP1-independent energy dissipation at thermoneutrality.

PATIENT DOSIMETRY SURVEY OF PEDIATRIC DIAGNOSTIC AND THERAPEUTIC CARDIAC CATHETERISATION IN JAPAN.

To propose reference values for air-kerma at the reference point (Ka,r), air-kerma area product (PKA), fluoroscopy time (FT) and number of cine images (CI) for four age groups in Japan, a nationwide questionnaire was posted to 132 pediatric catheterisation of certified facility in Japan, using the conventional post system, to which 43 facilities responded. For diagnostic cardiac angiography, reference values were as follows: Ka,r: 86, 102, 165 and 264 mGy; PKA: 9.3, 9.5, 16 and 34 Gy.cm2; FT: 33, 29, 26 and 30 min and CI: 1904, 1966, 2405 and 1871 images. For therapeutic cardiac angiography, reference values were as follows: Ka,r: 107, 163, 103 and 202 mGy; PKA: 7.5, 18, 7 and 24 Gy.cm2; FT: 56, 52, 42 and 30 min and CI: 3886, 3232, 2212 and 4316 images for less than 1, 1-5, 6-10 and 11-15 y, respectively. To optimal patient exposure from diagnostic and therapeutic cardiac catheterisation, it is therefore necessary to establish reference values for pediatric cardiac catheterisation examinations for four age groups.

NATIONWIDE SURVEY OF RADIATION EXPOSURE FOR RADIOFREQUENCY CATHETER ABLATION FOR PULMONARY VEIN ISOLATION AND NONPULMONARY VEIN ISOLATION IN JAPAN.

To propose typical values for the arrhythmia region between pulmonary vein isolation (PVI) and nonpulmonary vein isolation (non-PVI) in Japan. A nationwide questionnaire was posted to 343 facilities, to which 125 facilities (36.4%) responded. Results is the median for PVI and non-PVI were in terms of Ka,r (317 and 196 mGy), PKA (40.8 and 26.3 Gy.cm2), FT (43.0 and 27.3 min), and CI (326 and 102 images). When comparing PVI and non-PVI procedures, there were significant differences in Ka, r, PKA, FT, and CI (p < 0.05). In other words, by classifying into two types, PVI and non-PVI, we contributed to the establishment of typical values in Japan's RFCA.

USE OF VACUUM MATTRESSES CAN REDUCE THE ABSORBED DOSE DURING PEDIATRIC CT.

To evaluate and compare the absorbed dose and image quality when applying a commercially produced fixation device (group A) and a vaccum mattress fixation device to pediatric patients (group B). We compared the absorbed dose and image noise between the groups at the phantom and clinical study. For phantom study, the measurement absorbed dose for a real time skin dosimeter was 3.0 mGy at the group A and 1.9 mGy at the group B (p < 0.05). For clinical study, computed tomography dose index product, dose-length and effective radiation dose were significantly lower with the group B compared to the group A, (3.4 mGy, 27.0 mGy-cm, and 2.2 mSv vs 4.4 mGy, and 36.7 mGy-cm, and 3.0 mSv), p < 0.05 for all comparisons. Compared to the commercially produced fixation device, the vaccum mattress fixation device composed of a less absorptive material enabled a reduction in the absorbed dose while maintaining the image quality during pediatric CT examinations.

Dietary Supplementation with Dunaliella Tertiolecta Prevents Whitening of Brown Fat and Controls Diet-Induced Obesity at Thermoneutrality in Mice.

We investigated the effect of evodiamine-containing microalga Dunaliella tertiolecta (DT) on the prevention of diet-induced obesity in a thermoneutral C57BL/6J male (30 °C). It attenuates the activity of brown adipose tissue (BAT), which accelerates diet-induced obesity. Nine-week-old mice were fed a high-fat diet supplemented with 10 g (Low group) or 25 g (High group) DT powder per kg food for 12 weeks. Compared to control mice without DT supplementation, body weight gain was significantly reduced in the High group with no difference in food intake. Tissue analyses indicated maintenance of multilocular morphology in BAT and reduced fat deposition in liver in DT-supplemented mice. Molecular analysis showed a significant decrease in mammalian target of rapamycin-ribosomal S6 protein kinase signaling pathway in white adipose tissue and upregulation in mRNA expression of brown fat-associated genes including fibroblast growth factor-21 (Fgf21) and uncoupling protein 1 (Ucp1) in BAT in the High group compared to the control. In the experiments using C3H10T1/2 adipocytes, DT extract upregulated mRNA expression of brown fat-associated genes in dose-dependent and time-dependent manners, accompanied by a significant increase in secreted FGF21 levels. Our data show the ability of DT as a nutraceutical to prevent brown fat attenuation and diet-induced obesity in vivo.

[Nationwide Survey of Medical Radiation Exposure on Cardiovascular Examinations in Japan].

PURPOSE: It is very important to manage the radiation dose of cardiovascular interventional (CVI) procedures. Overseas, the diagnostic reference levels for cardiac interventional procedures were established with the air kerma at the patient entrance reference point (Ka,r) and the air kerma-area product (PKA). Although the Japan DRLs 2015 was established by the Japan Network for Research and Information on Medical Exposure (J-RIME), the Japan DRL for CVIs were established by fluoroscopic dose rates of 20 mGy/min at the patient entrance reference point with 20 cm thickness polymethyl methacrylate (PMMA) phantom. In the present our study, we performed a questionnaire survey of indicated values of angiographic parameters in CVI procedures. METHODS: A nationwide questionnaire was sent by post to 765 facilities. Question focused on angiographic technology, exposure parameters and radiation doses as the displayed dosimetric parameters on the angiographic machine. RESULTS: The recovery rate was 22.8% at 175 out of 765 facilities. In total 1728 cases of the coronary angiography (CAG), 1703 cases of the percutaneous coronary intervention (PCI), 962 cases of the radiofrequency catheter ablation (RFCA) and 377 cases of pediatric CVI. The 75th percentile value of Ka,r, PKA, fluoroscopy time (FT) and number of cine images (CI) for CAG, PCI, RFCA and pediatric CVI were 702, 2042, 644, and 159 mGy, respectively, 59.3, 152, 81.3, and 14.9 Gy・cm2, respectively, 10.2, 35.6, 61.1, and 35.6 min, respectively and 1503, 2672, 722, and 2378 images, respectively. Our investigation showed that the angiographic parameters were different in several CVI procedures. CONCLUSIONS: The displayed dosimetric parameters on the angiographic machine in CVI procedures showed different values. We should classify the dosimetric parameters for each procedure.

Contrast enhancement on 100- and 120 kVp hepatic CT scans at thin adults in a retrospective cohort study: Bayesian inference of the optimal enhancement probability.

PURPOSE: To assess the probability of achieving optimal contrast enhancement in 100 kVp and 120 kVp-protocol on hepatic computed tomography (CT) scans. MATERIALS AND METHODS: We enrolled 200 patients in a retrospective cohort study. Hundred patients were scanned with 120 kVp setting, and other 100 patients were scanned with 100 kVp setting. We measured the CT number in the abdominal aorta and hepatic parenchyma on unenhanced scans and hepatic arterial phase (HAP)-, and portal venous phase (PVP). The aortic enhancement at HAP and the hepatic parenchymal enhancement at PVP were compared between the two scanning protocols. Bayesian inference was used to assess the probability of achieving optimal contrast enhancement in each protocol. RESULTS: The Bayesian analysis indicated that when 100 kVp-rotocol was used, the probability of achieving optimal aortic enhancement (>280 HU) was 98.8% ±â€Š0.6%, whereas it was 88.7% ±â€Š2.5% when 120 kVp-protocol was used. Also, the probability of achieving optimal hepatic parenchymal enhancement (>50 HU) was 95.3% ±â€Š1.5%, whereas it was 64.7% ±â€Š3.8% when 120 kVp-protocol was used. CONCLUSION: Bayesian inference suggested that the post-test probability of optimal contrast enhancement at hepatic dynamic CT was lower under the 120 kVp than the 100 kVp-protocol.

[Usefulness of Fenestrated Catheters for i.v. Contrast Infusion Cardiac CT Angiography for Newborn Patients during the Congenital Heart Disease].

PURPOSE: A three-dimensional (3D) image from computed tomography (CT) angiography is a useful method for evaluation of complex anatomy such as congenital heart disease. However, 3D imaging requires high contrast enhancement for distinguishing between blood vessels and soft tissue. To improve the contrast enhancement, many are increasing the injection rate. However, one method is the use of fenestrated catheters, it allows use of a smaller gauge catheter for high-flow protocols. The purpose of this study was to compare the pressure of injection rate and CT number of a 24-gauge fenestrated catheter with an 22-gauge non-fenestrated catheter for i.v. contrast infusion during CT. METHODS: Between December 2014 and March 2015, 50 newborn patients were randomly divided into two protocols; 22-gauge conventional non-fenestrated catheter (24 newborn; age range 0.25-8 months, body weight 3.6±1.2 kg) and 24-gauge new fenestrated catheter (22 newborn; age range 0.25-12 months, body weight 3.3±0.9 kg). Helical scan of the heart was performed using a 64-detector CT (LightSpeed VCT, GE Healthcare) (tube voltage 80 kV; detector configuration 64×0.625 mm, rotation time 0.4 s/rot, helical pitch 1.375, preset noise index for automatic tube current modulation 40 at 0.625 mm slice thickness). RESULTS: We compared the maximum pressure of injection rate, CT number of aortic enhancement, and CT number of pulmonary artery enhancement between both protocols. The median injection rate, CT number of aortic enhancement, and CT number of pulmonary artery enhancement were 0.9 (0.5-3.4) ml/s, 455.5 (398-659) HU, and 500.0 (437-701) HU in 22-gauge conventional non-fenestrated catheter and 0.9 (0.5-2.0) ml/s, 436.5 (406-632) HU, and 479.5 (445-695) HU in the 24-gauge fenestrated catheter, respectively. There are no significantly different between a 24-gauge fenestrated catheter and 22-gauge non-fenestrated catheters at injection rate and CT number. Maximum pressure of injection rate was lower with 24-gauge non-fenestrated catheters (0.33 kg/cm2) than 22-gauge non-fenestrated catheters (0.55 kg/cm2) (p<0.01Conclusion: A 24-gauge fenestrated catheter performs similarly to an 22-gauge non-fenestrated catheter with respect to i.v. contrast infusion and aortic enhancement levels and can be placed in most subjects whose veins are deemed insufficient for an 22-gauge catheter.

Does the Tube Voltage Affect the Characterization of Coronary Plaques on 100- and 120-kVp Computed Tomography Scans.

OBJECTIVE: The aim of this study was to compare the diagnostic performance of 100- and 120-kVp coronary computed tomography (CT) angiography (CCTA) scans for the identification of coronary plaque components. METHODS: We included 116 patients with coronary plaques who underwent CCTA and integrated backscatter intravascular ultrasound studies. On 100-kVp scans, we observed 24 fibrous and 24 fatty/fibrofatty plaques; on 120-kVp scans, we noted 27 fibrous and 41 fatty/fibrofatty plaques. We compared the fibrous and the fatty/fibrofatty plaques, the CT number of the coronary lumen, and the radiation dose on scans obtained at 100 and 120 kVp. We also compared the area under the receiver operating characteristic (ROC) curve of the coronary plaques on 100- and 120-kVp scans with their ROC curves on integrated backscatter intravascular ultrasound images. RESULTS: The mean CT numbers of fatty and fatty/fibrofatty plaques were 5.71 ± 36.5 and 76.6 ± 33.7 Hounsfield units (HU), respectively, on 100-kVp scans; on 120-kVp scans, they were 13.9 ± 29.4 and 54.5 ± 22.3 HU, respectively. The CT number of the coronary lumen was 323.1 ± 81.2 HU, and the radiation dose was 563.7 ± 81.2 mGy-cm on 100-kVp scans; these values were 279.3 ± 61.8 HU and 819.1 ± 115.1 mGy-cm on 120-kVp scans. The results of ROC curve analysis identified 30.5 HU as the optimal diagnostic cutoff value for 100-kVp scans (area under the curve = 0.93, 95% confidence interval = 0.87-0.99, sensitivity = 95.8%, specificity = 78.9%); for 120-kVp plaque images, the optimal cutoff was 37.4 HU (area under the curve = 0.87, 95% confidence interval = 0.79-0.96, sensitivity = 82.1%, specificity = 85.7%). CONCLUSIONS: For the discrimination of coronary plaque components, the diagnostic performance of 100- and 120-kVp CCTA scans is comparable.

Development and Validation of Generalized Linear Regression Models to Predict Vessel Enhancement on Coronary CT Angiography.

Objective: We evaluated the effect of various patient characteristics and time-density curve (TDC)-factors on the test bolus-affected vessel enhancement on coronary computed tomography angiography (CCTA). We also assessed the value of generalized linear regression models (GLMs) for predicting enhancement on CCTA. Materials and Methods: We performed univariate and multivariate regression analysis to evaluate the effect of patient characteristics and to compare contrast enhancement per gram of iodine on test bolus (ΔHUTEST) and CCTA (ΔHUCCTA). We developed GLMs to predict ΔHUCCTA. GLMs including independent variables were validated with 6-fold cross-validation using the correlation coefficient and Bland-Altman analysis. Results: In multivariate analysis, only total body weight (TBW) and ΔHUTEST maintained their independent predictive value (p < 0.001). In validation analysis, the highest correlation coefficient between ΔHUCCTA and the prediction values was seen in the GLM (r = 0.75), followed by TDC (r = 0.69) and TBW (r = 0.62). The lowest Bland-Altman limit of agreement was observed with GLM-3 (mean difference, -0.0 ± 5.1 Hounsfield units/grams of iodine [HU/gI]; 95% confidence interval [CI], -10.1, 10.1), followed by ΔHUCCTA (-0.0 ± 5.9 HU/gI; 95% CI, -11.9, 11.9) and TBW (1.1 ± 6.2 HU/gI; 95% CI, -11.2, 13.4). Conclusion: We demonstrated that the patient's TBW and ΔHUTEST significantly affected contrast enhancement on CCTA images and that the combined use of clinical information and test bolus results is useful for predicting aortic enhancement.

Radiation Dose Reduction With a Low-Tube Voltage Technique for Pediatric Chest Computed Tomographic Angiography Based on the Contrast-to-Noise Ratio Index.

INTRODUCTION: The aim of this study was to evaluate the radiation dose and image quality at low tube-voltage pediatric chest computed tomographic angiography (CTA) that applies the same contrast-to-noise ratio (CNR) index as the standard tube voltage technique. MATERIALS AND METHODS: Contrast-enhanced chest CTA scans of 100 infants were acquired on a 64-row multidetector computed tomography (MDCT) scanner. In the retrospective study, we evaluated 50 images acquired at 120 kVp; the image noise level was set at 25 Hounsfield units. In the prospective study, we used an 80-kVp protocol; the image noise level was 40 Hounsfield units because the iodine contrast was 1.6 times higher than on 120-kVp scans; the CNR was as in the 120-kVp protocol. We compared the CT number, image noise, CT dose index volume (CTDIvol), and the dose-length product on scans acquired with the 2 protocols. A diagnostic radiologist and a pediatric cardiologist visually evaluated all CTA images. RESULTS: The mean CTDIvol and the mean dose-length product were 0.5 mGy and 7.8 mGy-cm for 80- and 1.2 mGy and 20.8 mGy-cm for 120-kVp scans, respectively (P < .001). The mean CTDIvol was 42% lower at 80 kVp than at 120 kVp, and there was no significant difference in the visual scores assigned to the CTA images (P = .28). CONCLUSIONS: With the CNR index being the same at 80-kVp and 120-kVp imaging, the radiation dose delivered to infants subjected to chest CTA can be reduced without degradation of the image quality.

Effect of Patient Characteristics on Vessel Enhancement at Lower Extremity CT Angiography.

Objective: To evaluate the effect of patient characteristics on popliteal aortic contrast enhancement at lower extremity CT angiography (LE-CTA) scanning. Materials and Methods: Prior informed consent to participate was obtained from all 158 patients. All were examined using a routine protocol; the scanning parameters were tube voltage 100 kVp, tube current 100 mA to 770 mA (noise index 12), 0.5-second rotation, 1.25-mm detector row width, 0.516 beam pitch, and 41.2-mm table movement, and the contrast material was 85.0 mL. Cardiac output (CO) was measured with a portable electrical velocimeter within 5 minutes of starting the CT scan. To evaluate the effects of age, sex, body size, CO, and scan delay on the CT number of popliteal artery, the researchers used multivariate regression analysis. Results: A significant positive correlation was seen between the CT number of the popliteal artery and the patient age (r = 0.39, p < 0.01). A significant inverse correlation was observed between the CT number of the popliteal artery and the height (r = -0.48), total body weight (r = -0.52), body mass index (r = -0.33), body surface area (BSA) (r = -0.56), lean body weight (r = -0.56), and CO (r = -0.35) (p < 0.001 for all). There was no significant correlation between the enhancement and the scan delay (r = 0.06, p = 0.47). The BSA, CO, and age had significant effects on the CT number (standardized regression: BSA -0.42, CO -0.22, age 0.15; p < 0.05, respectively). Conclusion: The BSA, CO, and age are significantly correlated with the CT number of the popliteal artery on LE-CTA.

Radiation Dose Reduction at Low Tube Voltage CCTA Based on the CNR Index.

RATIONALE AND OBJECTIVES: We compared the radiation dose and diagnostic accuracy on 120- and 100-kVp coronary computed tomography angiography (CCTA) scans whose contrast-to-noise ratio (CNR) was the same. MATERIALS AND METHODS: We studied 1311 coronary artery segments from 100 patients. For 120-kVp scans, the targeted image level was set at 25 Hounsfield units (HU). For 100-kVp scans, the targeted noise level was set at 30 HU to obtain the same CNR as at 120 kVp. We compared the CNR and the radiation dose on scans acquired at 120 and 100 kVp. Invasive coronary angiography (ICA) images were evaluated by an interventional coronary angiography specialist, and CCTA images were evaluated by a radiologist. Coronary artery disease was defined as a luminal narrowing ≧50% for ICA and CCTA. With ICA considered the gold standard, the diagnostic accuracy (sensitivity, specificity, positive predictive value, and negative predictive value) was analyzed on both 120- and 100-kVp CCTA images. We also compared the diagnostic accuracy for area under the receiver operating characteristic curve of the ICA and CCTA performed at 120 and 100 kVp. Two blinded observers visually evaluated the septal branch. RESULTS: The mean dose-length product was 48% lower at 100 kVp than at 120 kVp (P < .01). Under the 120-kVp CCTA protocol, the area under the curve, 95% confidence interval, sensitivity, specificity, positive predictive value, and negative predictive value were 0.94%, 0.91%-0.96%, 94.0%, 93.0%, 82.3%, and 98.1%, respectively; at 100 kVp these values were 0.94%, 0.92%-0.97%, 96.1%, 92.0%, 85.2%, and 98.0%, respectively. Area under the receiver operating characteristic curve analysis revealed no significant difference in diagnostic accuracy between the two protocols (P = .87). CONCLUSIONS: At the same CNR, the 100-kVp CCTA protocol may help to reduce the radiation dose by approximately 50% compared to the 120-kVp protocol without degradation of diagnostic accuracy.

Vessel Visibility Assessment of Low Tube Voltage Coronary Computed Tomography Angiography Determined with Contrast-to-Noise Ratio.

PURPOSE: The purpose of this study was to investigate the association of vessel visibility and radiation dose using contrast-to-noise ratio (CNR) method with low tube voltage in coronary computed tomography angiography (c-CTA). METHODS: We performed electrocardiogram-gated scan of 2.0-mm diameter simulated vessel in the center of the cardiac phantom by the use of a 64-detector CT scanner. Reference CNR was calculated from the target coronary CT number (CTnumberA; 350 Hounsfield units [HU]), epicardial fat CT number (CTnumberB; -100 HU), and target epicardial fat standard deviation (SD) number (SDB; 25 HU) at the 120 kV. We obtained the tube current at low tube voltage (100 and 80 kV) to perform the similar reference CNR at 120 kV. The full widths at half maximum from axial images were evaluated with quantitative evaluation and three types of visualizations of the vessel phantom were evaluated with the qualitative evaluations. RESULTS: CTnumberA of 100 and 80 kV were increased by 26% and 50%, respectively, compared with 120 kV (P<0.01). SDB was also increased by a similar ratio (P<0.01). CTDIvol of 100 and 80 kV were decreased by 39% and 51%, respectively, compared with 120 kV (P<0.05). There were no significant voltage differences among three tubes in quantitative and qualitative evaluations at the same CNR (P> 0.05). CONCLUSION: In this phantom study, these results show that the CNR method with low tube voltage achieves radiation dose reduction without decreasing the image quality.

[Study of CT Automatic Exposure Control System (CT-AEC) Optimization in CT Angiography of Lower Extremity Artery by Considering Contrast-to-Noise Ratio].

PURPOSE: To evaluate the image quality and effect of radiation dose reduction by setting for computed tomography automatic exposure control system (CT-AEC) in computed tomographic angiography (CTA) of lower extremity artery. METHODS: Two methods of setting were compared for CT-AEC [conventional and contrast-to-noise ratio (CNR) methods]. Conventional method was set noise index (NI): 14and tube current threshold: 10-750 mA. CNR method was set NI: 18, minimum tube current: (X+Y)/2 mA (X, Y: maximum X (Y)-axis tube current value of leg in NI: 14), and maximum tube current: 750 mA. The image quality was evaluated by CNR, and radiation dose reduction was evaluated by dose-length-product (DLP). RESULTS: In conventional method, mean CNRs for pelvis, femur, and leg were 19.9±4.8, 20.4±5.4, and 16.2±4.3, respectively. There was a significant difference between the CNRs of pelvis and leg (P<0.001), and between femur and leg (P<0.001). In CNR method, mean CNRs for pelvis, femur, and leg were 15.2±3.3, 15.3±3.2, and 15.3±3.1, respectively; no significant difference between pelvis, femur, and leg (P=0.973) in CNR method was observed. Mean DLPs were 1457±434 mGy⋅cm in conventional method, and 1049±434 mGy·cm in CNR method. There was a significant difference in the DLPs of conventional method and CNR method (P<0.001). CONCLUSION: CNR method gave equal CNRs for pelvis, femur, and leg, and was beneficial for radiation dose reduction in CTA of lower extremity artery.

The N-terminal motif of PMP70 suppresses cotranslational targeting to the endoplasmic reticulum.

Many membrane proteins possessing hydrophobic transmembrane (TM) segments are cotranslationally integrated into the endoplasmic reticulum (ER) membrane. Various peroxisomal and mitochondrial membrane proteins escape the ER-targeting mechanism and are targeted to their destinations. Here, we discovered a short segment in the 70-kDa peroxisomal membrane protein (PMP70) that suppresses ER targeting. The first TM segment has an intrinsic signal function that targets the nascent chain to the ER. The ER targeting was suppressed by a short N-terminal sequence of nine residues that is 80 residues upstream of the TM segment. Among the nine residues, Ser(5) is indispensable. The short segment also suppressed the signal peptide function of an authentic secretory protein. This function of the short segment was suppressed by the recombinant motif-GST fusion protein. The 50-kDa and 20-kDa proteins were crosslinked with the motif. The PMP70 molecule with the Ser5Ala point mutation predominantly localized to the ER. We propose the concept of an ER-targeting suppressor that suppresses the ER-targeting mechanism via a binding factor.

Delivering the Saline Chaser Via a Spiral Flow-Generating Tube Improves Arterial Enhancement for Computed Tomography Angiography of the Lower Extremities.

RATIONALE AND OBJECTIVES: We delivered the saline chaser via a spiral flow-generating tube or a conventional connecting tube and compared arterial enhancement at computed tomography angiography (CTA) of the lower extremities. MATERIALS AND METHODS: We randomly assigned 100 patients whose ankle bronchial pressure index or clinical symptoms were suspect of peripheral arterial disease to a spiral flow-generating tube (protocol A) or a conventional connecting-tube protocol (protocol B) and performed CTA of the lower extremities. The test bolus was delivered under protocol A or B, and the CT numbers recorded for each protocol were compared. Two radiological technologists visually evaluated the descending genicular artery. RESULTS: In the test injection, the median CT number for the popliteal artery was significantly higher with protocol A than B (204.5 HU vs. 170.5 HU, P = 0.03). For CTA of the lower extremities, the median CT number for the popliteal artery at the level of the patella was 436.1 HU (range, 259-608 HU) under protocol A; with protocol B, it was 382.9 HU (range, 244-564 HU) (P = 0.02). The visual score assigned in the descending genicular artery was statistically significantly higher under protocol A than B (P = 0.03). CONCLUSIONS: Use of the spiral flow-generating tube increased the effect of the saline chaser and significantly improved arterial enhancement from the abdominal aorta to the arteries of the foot at CTA of the lower extremities.

Evodiamine inhibits insulin-stimulated mTOR-S6K activation and IRS1 serine phosphorylation in adipocytes and improves glucose tolerance in obese/diabetic mice.

Evodiamine, an alkaloid extracted from the dried unripe fruit of the tree Evodia rutaecarpa Bentham (Rutaceae), reduces obesity and insulin resistance in obese/diabetic mice; however, the mechanism underlying the effect of evodiamine on insulin resistance is unknown. This study investigated the effect of evodiamine on signal transduction relating to insulin resistance using obese/diabetic KK-Ay mice and an in vitro adipocyte culture. There is a significant decrease in the mammalian target of rapamycin (mTOR) and ribosomal S6 protein kinase (S6K) signaling in white adipose tissue (WAT) in KK-Ay mice treated with evodiamine, in which glucose tolerance is improved. In addition, reduction of insulin receptor substrate 1 (IRS1) serine phosphorylation, an indicator of insulin resistance, was detected in their WAT, suggesting suppression of the negative feedback loop from S6K to IRS1. As well as the stimulation of IRS1 and Akt serine phosphorylation, insulin-stimulated phosphorylation of mTOR and S6K is time-dependent in 3T3-L1 adipocytes, whereas evodiamine does not affect their phosphorylation except for an inhibitory effect on mTOR phosphorylation. Moreover, evodiamine inhibits the insulin-stimulated phosphorylation of mTOR and S6K, leading to down-regulation of IRS1 serine phosphorylation in the adipocytes. Evodiamine also stimulates phosphorylation of AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, which may cause down-regulation of mTOR signaling in adipocytes. A similar effect on AMPK, mTOR and IRS1 phosphorylation was found in adipocytes treated with rosiglitazone. These results suggest evodiamine improves glucose tolerance and prevents the progress of insulin resistance associated with obese/diabetic states, at least in part, through inhibition of mTOR-S6K signaling and IRS1 serine phosphorylation in adipocytes.

[The comparison between dose rates at the interventional reference point of the angiography systems in many facilities].

The management of the radiation dose is very important in interventional radiology (IVR), especially in percutaneous coronary intervention (PCI). Therefore, we measured entrance surface doses at the interventional reference point of 27 cardiac intervention procedures in 22 cardiac catheterization laboratories around Hiroshima, and compared these doses. Recently, for cardiac interventional radiology, the X-ray machines using flat-panel detectors (FPD) instead of image intensifiers (I.I.) is increasing; 13 systems used FPD and 14 systems used I.I. For fluoroscopy rate, the difference between laboratories was 9 times. For cineangiography rate, the difference between laboratories was 7 times. In addition, between both devices, the I.I. group is bigger than the FPD group. When comparing by the same condition, for the dose at the interventional reference point, no significant difference was detected between the FPD group and the I.I. group. This study shows that FPD is not available for reducing the radiation dose simply. Therefore, it is necessary that we think of the balance with image quality and radiation dose. The optimization of the devices and cardiac intervention procedures becomes very important.