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The aim of this study is to fabricate nanophotosensitizers composed of methoxy poly(ethylene glycol) (mPEG), chlorin e6 (Ce6), and phenylboronic acid pinacol ester (PBAP) with diselenide linkages for reactive oxygen species (ROS)-sensitive photodynamic therapy (PDT) of cervical cancer cells. To fabricate nanophotosensitizers, Ce6 was conjugated with mPEG via selenocystamine linkage and then remaining carboxylic acid groups of Ce6 was attached to PBAP (mPEGseseCe6PBAP conjugates). Nanophotosensitizers of mPEGseseCe6PBAP conjugates were prepared by dialysis method. In transmission electron microscope (TEM) observation, nanophotosensitizers of mPEGseseCe6PBAP conjugates have spherical shapes and their diameters were less than 150 nm. The average diameter of mPEGseseCe6PBAP nanophotosensitizers was 92.7 ± 9.6 nm in particle size analysis. When H2O2 was added to the nanophotosensitizer solution, nanophotosensitizers were sensitively disintegrated according to the H2O2 concentration and then changed from monomodal distribution to multimodal distribution in particle size distribution. Furthermore, Ce6 release from nanophotosensitizers also increased according to the H2O2 concentration. When H2O2 was added to cell culture of HeLa human cervical cancer cells, intracellular Ce6 uptake of nanophotosensitizers were gradually increased according to the H2O2 concentration, indicating that nanophotosensitizers showed ROS-sensitive delivery of Ce6 against cancer cells.As well as free Ce6, nanophotosensitizers in the absence of light irradiation have low intrinsic cytotoxicity against RAW264.7 cells and HeLa cells. However, nanophotosensitizers induced cell death dose-dependently under light irradiation. Especially, nanophotosensitizers showed significantly higher ROS generation and phototoxicity against HeLa cells in vitro. When nanophotosensitizers were intravenously administered to animal tumor xenograft model of HeLa cells, tumor tissues revealed stronger fluorescence intensity than other tissues by light irradiation while absence of light irradiation induced relatively lower fluorescence intensity in tumor tissues, indicating that nanophotosensitizers have sensitivity against oxidative stress in tumor tissues. We suggest that nanophotosensitizers of mPEGseseCe6PBAP conjugates are promising vehicle for PDT of cervical cancer cells.

BACKGROUND The infusion of triolein emulsion (TE) induced increased vascular permeability and a negligible and temporary decrease in liver function without specific histopathological damage. AIM To assess changes in doxorubicin concentration according to the percentage of TE infused via a hepatic artery to study the vascular permeability in the rabbit liver. METHODS Thirty-nine healthy rabbits were divided into five groups according to the concentration of emulsified triolein infused into the hepatic arteries: Group 0, saline infusion (control group, n = 5); group 1, 0.3% TE (n = 13); group 2, 0.6% TE (n = 6); group 3, 0.9% TE (n = 8); and group 4, 1.5% TE (n = 6). Doxorubicin (2.4 mg/kg) was infused immediately after TE injection via the hepatic arteries. After 2 h, the livers were harvested, and doxorubicin concentrations were calculated fluorometrically. The doxorubicin concentrations were compared between TE groups and the control group, and the optimal concentrations within the TE groups were calculated. Statistical analysis was performed using the nonparametric Mann-Whitney U test and Kruskal–Wallis test. P < 0.05 were considered statistically significant. RESULTS In the liver, doxorubicin concentrations were 2.06, 2.07, 2.16 and 1.66 times higher in groups 1 through 4, respectively, and significantly higher in the TE groups than in the control group (all P < 0.05). However, there were no significant differences in the mean doxorubicin concentrations between the four TE groups (P = 0.642). In the lungs, the mean doxorubicin concentrations were not significantly different between the control and TE groups (P > 0.05). CONCLUSION TE infusion into the hepatic arteries significantly increased the doxorubicin concentration approximately twofold but was not different between the TE groups. These findings suggest that TE infusion might be a useful adjuvant treatment of liver cancers.

Purpose To evaluate the enhancement of temozolomide (TMZ) delivery in the rat brain using a triolein emulsion. Materials and Methods Rats were divided into the five groups as following: group 1 (negative control), group 2 (treated with triolein emulsion and TMZ 20 mg/kg), and group 3 (TMZ 20 mg/kg treatment without triolein), group 4 (treated with triolein emulsion and TMZ 10 mg/kg), and group 5 (TMZ 10 mg/kg treatment without triolein). Triolein emulsion was infused into the right common carotid artery. One hour later, the TMZ concentration was evaluated quantitatively and qualitatively using high-performance liquid chromatography (HPLC-MS) and desorption electrospray ionization mass spectrometry (DESI-MS) imaging, respectively. The concentration ratios of the ipsilateral to contralateral hemisphere in each group were determined and the statistical analysis was conducted using an unpaired t-test. Results Quantitatively, the TMZ concentration ratio of the ipsilateral to the control hemisphere was 2.41 and 1.13 in groups 2 and 3, and were 2.49 and 1.14 in groups 4 and 5, respectively. Thus, the TMZ signal intensities of TMZ in group 2 and 4 were statistically high in the ipsilateral hemispheres. Qualitatively, the signal intensity of TMZ was remarkably high in the ipsilateral hemisphere in group 2 and 4. Conclusions The triolein emulsion efficiently opened the blood-brain barrier and could provide a potential new strategy to enhance the therapeutic effect of TMZ. HPLC-MS and DESI-MS imaging were shown to be suitable for analyses of enhancement of brain TMZ concentrations.

Background Cerebral angiography in a rabbit model is widely used in the field of interventional radiology. Conventionally, the femoral artery is used for cerebral angiography in radiology departments. However, angiographic studies require surgical cutdown of the femoral artery, which is technically difficult. Purpose To evaluate a new cerebral angiography technique involving a transauricular approach in a rabbit model. Material and Methods In each of 10 rabbits, central auricular arteries were punctured in the right or left ear with a 20-gauge i.v. catheter. A microcatheter (2.0 F) with a 0.016-inch guide wire was introduced through the i.v. catheter and advanced to the aortic arch. The microcatheter and guide wire were advanced selectively into cerebral arteries and angiography was performed. Results Central auricular arteries were successfully punctured with 20-gauge i.v. catheters. After approaching the aortic arch, microcatheter tips and guide wires were advanced manually to cerebral arteries on both sides. Difficulties in selecting the carotid arteries were resolved by using a looping technique within the cardiac chamber. Microcatheter loops within the cardiac chamber disappeared or remained during artery superselection. Conclusion Transauricular cerebral angiography appears to be a feasible technique for brain or carotid intervention studies in rabbits. In addition, vertebral angiography using a transauricular approach is possible using the looping technique. Selection of carotid or vertebral arteries on each side was not difficult when the microcatheter and guide wire were looped within the cardiac chamber. The ear chosen for the initial puncture does not appear to be important.

In this study, we designed and synthesized a highly stable manganese (Mn2+)-based hepatobiliary complex by tethering an ethoxybenzyl (EOB) moiety with an ethylenediaminetetraacetic acid (EDTA) coordination cage as an alternative to the well-established hepatobiliary gadolinium (Gd3+) chelates and evaluated its usage as a T1 hepatobiliary magnetic resonance imaging (MRI) contrast agent (CA). This new complex exhibits higher r1 relaxivity (2.3 mM-1 s-1) than clinically approved Mn2+-based hepatobiliary complex Mn-DPDP (1.6 mM-1 s-1) at 1.5 T. Mn-EDTA-EOB shows much higher kinetic inertness than that of clinically approved Gd3+-based hepatobiliary MRI CAs, such as Gd-DTPA-EOB and Gd-BOPTA. In addition, in vivo biodistribution and MRI enhancement patterns of this new Mn2+ chelate are comparable to those of Gd3+-based hepatobiliary MRI CAs. The diagnostic efficacy of the new complex was demonstrated by its enhanced tumor detection sensitivity in a liver cancer model using in vivo MRI.

Triolein emulsion has been known to increase vascular permeability in the brain when it is infused into the carotid artery. The purpose of this study was to identify the morphologic mechanism of increased vascular permeability in brain induced by infusion of emulsified triolein into the carotid artery by transmission electron microscopy (TEM). Triolein emulsion was infused into the carotid artery of rats. TEM using lanthanum tracer was used to evaluate morphologic changes in endothelium with a focus on transcytotic vesicles and tight junction opening. The treat group showed multiple transcytotic vesicles containing lanthanum tracer within endothelium on TEM. TEM also revealed that lanthanum tracer entered neural interstitium through tight junctions between capillary endothelial cells infrequently in the treat group. No evidence of transcytotic vesicles containing lanthanum tracer or lanthanum leakage through tight junctions was observed in the control group. Transcytosis and the opening of tight junctions appears the pathway for vascular permeability enhancement by triolein. This result could be utilized in studies on the blood-brain barrier and by those searching for chemotherapeutic methods that deliver anti-tumor agents to normally drug inaccessible organs.

Aim: The purpose of this study was to assess changes in doxorubicin concentration in rabbit brain with respect to time after BBB opening induced by triolein emulsion infusion via a carotid artery a...

We synthesized phenylboronic acid pinacol ester (PBPE)-conjugated hyaluronic acid (HA) via thiobis(ethylamine) (TbEA) linkage (abbreviated as HAsPBPE conjugates) to fabricate the radiosensitive delivery of caffeic acid phenetyl ester (CAPE) and for application in radioprotection. PBPE was primarily conjugated with TbEA and then PBPE-TbEA conjugates were conjugated again with hyaluronic acid using carbodiimide chemistry. CAPE-incorporated nanoparticles of HAsPBPE were fabricated by the nanoprecipitation method and then the organic solvent was removed by dialysis. CAPE-incorporated HAsPBPE nanoparticles have a small particle size of about 80 or 100 nm and they have a spherical shape. When CAPE-incorporated HAsPBPE nanoparticles were irradiated, nanoparticles became swelled or disintegrated and their morphologies were changed. Furthermore, the CAPE release rate from HAsPBPE nanoparticles were increased according to the radiation dose, indicating that CAPE-incorporated HAsPBPE nanoparticles have radio-sensitivity. CAPE and CAPE-incorporated HAsPBPE nanoparticles appropriately prevented radiation-induced cell death and suppressed intracellular accumulation of reactive oxygen species (ROS). CAPE and CAPE-incorporated HAsPBPE nanoparticles efficiently improved survivability of mice from radiation-induced death and reduced apoptotic cell death. We suggest that HAsPBPE nanoparticles are promising candidates for the radio-sensitive delivery of CAPE.

Background Directly measured low density lipoprotein cholesterol (DLDLC) has been reported to be more accurate than calculated low density lipoprotein cholesterol (CLDLC) using the Friedewald equation. However, some limitations of DLDLC have been reported. In this study, we evaluated differences between CLDLC and DLDLC measured using HiSens reagents. Methods Data were collected from 582 persons undergoing routine physical examinations at a general hospital. LDLC measurements were made directly or estimated using the Friedewald formula, and were classified according to the National Cholesterol Education Program's Adult Treatment Panel III guidelines. The relationship between these differences and other clinically relevant factors, such as triglyceride (TG) levels, were examined using multiple logistic regression analysis. Results The DLDLC and CLDLC were strongly correlated according to simple linear regression analysis (r=0.917, P0.5). Conclusion Unlike other studies, DLDLC was significantly lower than CLDLC and the large differences in LDLC concentrations were not dependent on TG concentration. Our work suggests that verification of DLDLC accuracy is needed and differences in LDLC measurements should be accounted for in making clinical decisions.

A sensitive and rapid liquid chromatography positive ion electrospray ionization tandem mass spectrometric (LC/ESI-MS/MS) method has been developed and validated for the quantitative determination and distribution of cisplatin (CP) in kidney and liver tissues after intravenous administration of drug to adult male Sprague Dawley rats. Oxaliplatin (OXP) was used as an internal standard. The tissue samples were homogenized and extracted using conventional liquid–liquid extraction method with phosphate buffer containing ethyl acetate and then subjected to LC-MS analysis. The chromatographic separation was achieved on an Agilent ZORBAX SB C-18 column (50 × 2.1 mm, 1.8 µm) using the mobile phase consisting of 0.1% formic acid in water (Solvent A) : methanol (Solvent B) (40 : 60; v/v) in an isocratic elution followed by detection with positive ion electrospray ionization tandem mass spectrometry using the transitions of m/z 301 > 265 for CP and m/z 398 > 310 for OXP in multiple reaction monitoring mode. The calibration curve was linear in the range of 5.0–7000 and 10.0–6000 ng/ml for kidney and liver tissue homogenates, respectively. The method revealed good performances in terms of within-batch, between-batch precision (1.31–5.70%) and accuracy (97.0–102.24%) for CP in both kidney and liver tissue homogenates including lower and upper limits of quantification. The recoveries from spiked control samples were >81.0% and >87.0 % for CP and OXP, respectively. Matrix effect was found to be negligible, and the stability data were within the acceptable limits. Further, the validated LC/ES-MS/MS method was successfully applied to investigate the distribution of CP in kidney and liver tissues after intravenous administration of CP to male Sprague Dawley rats. The results showed that the higher amount of CP was distributed in kidney followed by liver, which indicated that CP mainly accumulated in kidney tissues and renal excretion might be a primary and main elimination route. This is the first research approach focused on the quantitative determination and distribution of CP in rat kidney and liver tissue homogenates by using LC/ESI-MS/MS, which could provide essential information for further pharmacological and clinical studies of CP. Copyright © 2015 John Wiley & Sons, Ltd.

The aim of this study is to fabricate caffeic acid phenethyl ester (CAPE)-incorporated nanoparticles using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (CE) copolymer and to study their antitumor activity against pulmonary metastasis model of CT26 colon carcinoma cells. CAPE-incorporated nanoparticles showed spherical shapes having small diameters less than 300 nm and CAPE was continuously released from CE nanoparticles over 4 days. CAPE-incorporated polymeric micelles properly inhibited proliferation and induced apoptosis of CT26 cells as well as CAPE itself. Furthermore, they showed similar anti-invasive and antimigrative effect against CT26 cells at in vitro compared with CAPE itself, indicating that CAPE-incorporated nanoparticles have at least equivalent anticarcinogenic activity against CT26 cells compared with CAPE itself. At pulmonary metastasis model of CT26 cells using nude mouse, CAPE-incorporated nanoparticles have superior antimetastatic efficacy against, that is, control treatment with pulmonary metastasis model showed significant increase of lung weight because of the metastasis of tumor cells, whereas CAPE or CAPE-incorporated nanoparticles properly inhibited metastasis of tumor cells. We suggest CAPE-incorporated nanoparticles as a promising candidate for antimetastatic chemotherapeutic agent. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:144-154, 2015.

Folic acid-decorated self-organized nanoparticles were fabricated to target folate receptor of cancer cells. Doxorubicin (DOX) was conjugated with carboxyl group of dextran backbone using succinic anhydride (DexSU-DOX). DOX-loaded self-organized nanoparticles were prepared by complexation with folic acid-grafted chitosan (ChitoFA) and DexSU-DOX. Nanoparticles in the aqueous environment have spherical shapes with average size less than 100 nm and their sizes were increased by coated with ChitoPEG or ChitoFA. At cell culture study with KB cells, ChitoFA coated nanoparticles (FADex NP) revealed folate-receptor mediated endocytosis to cancer cells and cell viability was significantly changed by folate receptor targeting. Tumor xenograft model of KB cells also showed similar results, i.e. FAdex NP efficiently inhibited growth of tumor compared to the treatment group with blocking of folate receptor. These results indicated that DOX-loaded nanoparticles of FADex NP are promising vehicle for anticancer drug targeting.

Biocompatible lipo-histidine hybrid materials conjugated with IR820 dye show pH-sensitivity, efficient intracellular delivery of doxorubicin (Dox), and intrinsic targetability to cancer cells. These new materials form highly uniform Dox-loaded nanosized vesicles via a self-assembly process showing good stability under physiological conditions. The Dox-loaded micelles are effective for suppressing MCF-7 tumors, as demonstrated in vitro and in vivo. The combined mechanisms of the EPR effect, active internalization, endosomal-triggered release, and drug escape from endosomes, and a long blood circulation time, clearly prove that the IR820 lipopeptide DDS is a safe theranostic agent for imaging-guided cancer therapy.

In order to know the effect of pre-existing Trichinella spiralis infection on experimentally induced intestinal inflammation and immune responses, we induced colitis in T. spiralis-infected mice and observed the severity of colitis and the levels of Th1, Th2, and regulatory cytokines and recruitment of CD4(+)CD25(+)Foxp3(+) T (regulatory T; T(reg)) cells. Female C57BL/6 mice were infected with 250 muscle larvae; after 4 weeks, induction of experimental colitis was performed using 3% dextran sulfate sodium (DSS). During the induction period, we observed severity of colitis, including weight loss and status of stool, and evaluated the disease activity index (DAI). A significantly low DAI and degree of weight loss were observed in infected mice, compared with uninfected mice. In addition, colon length in infected mice was not contracted, compared with uninfected mice. We also observed a significant increase in production of pro-inflammatory cytokines, IL-6 and IFN-γ, in spleen lymphocytes treated with DSS; however, such an increase was not observed in infected mice treated with DSS. Of particular interest, production of regulatory cytokines, IL-10 and transforming growth factor (TGF)-β, in spleen lymphocytes showed a significant increase in mice infected with T. spiralis. A similar result was observed in mesenteric lymph nodes (MLN). Subsets of the population of T(reg) cells in MLN and spleen showed significant increases in mice infected with T. spiralis. In conclusion, T. spiralis infection can inhibit the DSS-induced colitis in mice by enhancing the regulatory cytokine and T(reg) cells recruitment.

The present study was performed to estimate the seroprevalence of larval Anisakis simplex infection among the residents health-examined in 3 hospitals in southern parts of Korea. A total of 498 serum samples (1 serum per person) were collected in 3 hospitals in Busan Metropolitan city, Masan city, and Geoje city in Gyeongsangnam-do (Province) and were examined by IgE-ELISA and IgE-western blotting with larval A. simplex crude extract and excretory-secretory products (ESP). The prevalence of antibody positivity was 5.0% and 6.6% with ELISA against crude extracts and ESP, respectively. It was also revealed that infection occurred throughout all age groups and higher in females than in males. A specific protein band of 130 kDa was detected from 10 patients with western blot analysis against crude extract and ESP among those who showed positive results by ELISA. Our study showed for the first time the seroprevalence of anisakiasis in Korea. The allergen of 130 kDa can be a candidate for serologic diagnosis of anisakiasis.

The infection status of marine fish and cephalopods with Anisakis simplex third stage larva (L3) was studied over a period of 1 year. A total of 2,537 specimens, which consisted of 40 species of fish and 3 species of cephalopods, were purchased from the Cooperative Fish Market in Busan, Korea, from August 2006 to July 2007. They were examined for A. simplex L3 from the whole body cavity, viscera, and muscles. A. simplex L3 were confirmed by light microscopy. The overall infection rate reached 34.3%, and average 17.1 larvae were parasitized per infected fish. Fish that recorded the highest infection rate was Lophiomus setigerus (100%), followed by Liparis tessellates (90%), Pleurogrammus azonus (90%), and Scomber japonicus (88.7%). The intensity of infection was the highest in Gadus macrocephalus (117.7 larvae per fish), followed by S. japonicus (103.9 larvae) and L. setigerus (54.2 larvae). Although abundance of A. simplex L3 was not seasonal in most of the fish species, 10 of the 16 selected species showed the highest abundance in February and April. A positive correlation between the intensity of L3 infection and the fish length was obvious in S. japonicus and G. macrocephalus. It was likely that A. simplex L3 are more frequently infected during the spring season in some species of fish. Our study revealed that eating raw or undercooked fish or cephalopods could still be a source of human infection with A. simplex L3 in Korea.

This study was carried out to examine microbiological contamination of ready-to-eat products and to propose a draft-standard and specifications according to food types. RTE foods were classified into 6 groups including fish products, meat products, breads, rices, salads, and fresh cut foods. The prevalence rates of pathogens detected from all samples were compared among food categories. The pH ranges for all RTE samples were between 3.8 and 7.3. Total aerobic cell counts ranged from 2 to 6 log CFU/g. Bread, rice and fresh-cut foods showed significantly higher counts, which ranged above 4.0 log CFU/g among the samples. Two kinds of rice were above the level of the KFDA Food Code standard for Eschrichia coli. The prevalence rate of E. coli in the rice was 6.7%. For Staphylococcus aureus, one fish product and one bread-product had levels above 2 log CFU/g. Bacillus cereus counts for all samples were below the level of 3 log CFU/g. Listeria monocytogenes was not detected in the samples. Therefore, these data suggest that the primary microbial hazard factors for ready-to-eat foods and risk assessments should focus on E. coli, S. aureus, and B. cereus.

Hee Yun Kim, Se Jong Park*, So Young Chung, Seon Hee Choi, Sun Woo Oh, Jin Sook Lee,In Sun Choi, Min Su Shin, and Jae Sang SongHazard Substances Analysis Division, Seoul Regional Korea Food and Drug AdministrationAbstract The purpose of this study was to analyze the content and consumption of total sugar from school lunches atIncheon and Chuncheon. The samples were collected from eight elementary schools and eight middle schools in Incheonand Chuncheon for 15 days. The analysis of total sugar content was performed for 1334 main dishes, side dishes, anddesserts, which were supplied by elementary and middle school foodservices. Total sugar content was extracted fromvarious types of food with 50% ethanol after defatting. We simultaneously analyzed sugars such as fructose, glucose,sucrose, maltose, and lactose by a high performance liquid chromatography with refractive index detector. The averagelunch intake for elementary school and middle school students was 372.6±72.2 g and 449.2±81.1 g, respectively. The totalsugar content in desserts was 7.21±6.32 g/100 g, 1.69±2.44 g/100 g in side dishes, and 0.32±0.77 g/100 g in main dishes.Among side dishes, fried foods, stir-fried foods, and sauces contained the highest amounts of total sugar. The total sugarintake was 4.63±5.11 g in desserts, 0.64±1.01 g in side dishes, and 0.55±1.48 g in main dishes. Main and side dishes witha high total sugar intake included cooked rice with seasoning, fried foods, stir-fried foods, and preserved foods. Theaverage total sugar intake per meal for elementary school, middle school, and all students was 4.03±3.67 g, 6.97±6.59 g,and 5.50±5.53 g, respectively. We have provided useful information to decrease the intake of total sugar in school lunches.It is recommended that total sugar intake be continuously monitored.Keywords: total sugar content, intake, school, foodservice

The purpose of this study is to investigate immediate changes in the blood retinal barrier (BRB) after the infusion of triolein emulsion.Triolein emulsion was infused into the carotid artery of 12 cats to induce experimental fat embolism. The injection of fluorescein dye into the carotid artery followed immediately. Early retinal vascular flow was recorded by a fluorescein angiography (FA) video, and then a FA photograph was obtained up to 30 min after the injection. Leakage of the dye in the choroidal or retinal vessels was evaluated.In the early phase, multifocal non-perfuse areas were noted in all cats due to embolism by triolein emulsion, which was released by blood perfusion in the late phase. Perfusion defects persisted in the retina of five cats and in the choroid of four cats. Leakage of the dye through the retinal vessels was seen in five cats (42%) in the early phase and in nine cats (75%) in the late phase. In the choroid, leakage of the dye was seen in seven cats (58%) in the early phase and in all cats (100%) in the late phase.The inner and outer BRB was opened immediately after infusion of triolein emulsion into the carotid artery. Embolism by triolein emulsion was readily resolved due to the liquid nature of triolein.

We isolated a galectin-9 (Gal-9) homologue gene (Tl-gal) from an adult worm of the canine gastrointestinal nematode parasite, Toxascaris leonina, via random cDNA library sequencing. The deduced amino acid sequence of the Tl-gal genes evidenced an identity of 89% with the galectin of Dirofilaria immitis, 87% identity with the galectin of Brugia malayi, and 35% identity with the human GAL-9 gene. To evaluate immune modulate function of Tl-GAL in host inflammatory response, we constructed recombinant Tl-GAL (rTl-GAL) using an Escherichia coli expression vector system and treated to intestinal inflammation mice. Although the carbohydrate-binding ability of rTl-GAL was less than that of rat galectin, we confirmed that recombinant rTl-GAL has carbohydrate-binding activity. The clinical symptoms of dextran sulfate sodium (DSS)-treated mice after rTl-GAL pre-treatment were found to be minimized, or less profound, as compared to those of the rTl-GAL untreated group. Additionally, the DSS-treated mice exhibited a significant shortening of the colon, but the large intestines of the rTl-GAL pre-treated mice were longer than those of the control group (P

The national management and retrieval service of the national scholar Content DB are very important. High quality content can improve the user’s utilization and satisfaction and be a strong base for both the citation index creation and the calculation of journal impact factors. Therefore, the system is necessary to check data quality effectively. We have closely studied and developed a webbased data quality checking system that will support anything from raw digital data to its automatic validation as well as hands-on validation, all of which will be discussed in this paper.

Attractiveness of different amounts of methyl (E,E,Z)-2,4,6-decatrienoate, the aggregation pheromone of brown-winged stink bug, Plautia stali (Hemiptera: Pentatomidae), was tested using different kinds of dispensers. A lure filled with hexane was used as a control treatment. There were no differences in the attractiveness of the pheromone to P. stali and Halyomorpha halys among dispensers (polyethylene-vial, rubber septum, and polyethylene tube). Traps baited with 7, 20, 40, 50, and 60 mg of pheromone were tested for their attractiveness. For females, the 40 mg trap attracted highest number of P. stali, even though there were no significant differences among pheromone amounts. For males, the 40 and 50 mg traps attracted significantly more bugs than the 7, 20, and 60 mg traps and the control traps. Based on these results, the pheromone dispenser impregnated with 40 mg of pheromone will be practical in monitoring P. stali in the field.

We have cloned the macrophage migration inhibitory factor (MIF)-like protein (Anisakis simplex (As)-MIF) from larvae of the whale worm (Anisakis simplex third-stage larvae). Asthma was induced in the mice using OVA/alum, with or without various concentrations of rAs-MIF treatment before OVA/alum challenge. Treatment with rAs-MIF coupled with OVA/alum during the challenge period induced a complete inhibition of eosinophilia and goblet cell hyperplasia within the lung and profoundly ameliorated the development of lung hyperreactivity. Also, rAs-MIF was shown to reduce profoundly the quantity of Th2-related cytokines (IL-4, IL-5, and IL-13) in the bronchial alveolar lavage fluid and allergen-specific IgG2a in sera. IL-10 and TGF-β levels in the bronchoalveolar lavage fluid of the rAs-MIF-treated group were significantly higher than in the other groups. Additionally, CD4+CD25+Foxp3+ T cells (regulatory T) were recruited to the spleen and lungs of the rAs-MIF-treated mice, but this recruitment was inhibited by anti-rAs-MIF Ab.

BACKGROUND Triolein emulsion infusion into the carotid artery has been reported to induce temporary and reversible opening of the blood-brain barrier by increasing vascular permeability. OBJECTIVE To evaluate the effect of triolein emulsion infusion on brain permeance by anticancer agents. METHODS In the doxorubicin study. 2.4 mg/kg doxorubicin was injected immediately after triolein emulsion (1%, 1.5%, and 2%) infusion into rabbit carotid arteries. Two hours later, bilateral hemispheres and eyeballs were harvested, and doxorubicin concentrations were measured fluorometrically. Doxorubicin ratios of ipsilateral/contralateral hemispheres were compared with those of doxorubicin controls by use of the Kruskal-Wallis test followed by the Dunn test. In the cisplatin study, 10 mg/kg cisplatin was injected immediately after 2% triolein emulsion infusion into rat carotid arteries. Ipsilateral hemispheres were harvested 2, 6, 12, 24, and 36 hours after treatment. Time-dependent cisplatin concentrations were determined by liquid chromatography/electrospray ionization-tandem mass spectrometry/mass spectrometry. RESULTS Doxorubicin concentrations were significantly higher in ipsilateral hemispheres and eyeballs in all 3 triolein treatment groups than in doxorubicin controls. In the cisplatin study, cisplatin concentrations in the ipsilateral hemispheres peaked at 6 hours after infusion of cisplatin. CONCLUSION Brain permeance to anticancer agents was increased by triolein emulsion infusion, which suggests that triolein infusion might be a useful adjuvant treatment for brain tumors.

In vivo rat kidney tissue metabolites of an anticancer drug, cisplatin (cis-diamminedichloroplatinum [II]) (CP) which is used for the treatment of testicular, ovarian, bladder, cervical, esophageal, small cell lung, head and neck cancers, have been identified and characterized by using liquid chromatography positive ion electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) in combination with on line hydrogen/deuterium exchange (HDX) experiments. To identify in vivo metabolites, kidney tissues were collected after intravenous administration of CP to adult male Sprague-Dawley rats (n = 3 per group). The tissue samples were homogenized and extracted using newly optimized metabolite extraction procedure which involves liquid extraction with phosphate buffer containing ethyl acetate and protein precipitation with mixed solvents of methanol-water-chloroform followed by solid-phase clean-up procedure on Oasis HLB 3cc cartridges and then subjected to LC/ESI-HRMS analysis. A total of thirty one unknown in vivo metabolites have been identified and the structures of metabolites were elucidated using LC-MS/MS experiments combined with accurate mass measurements. Online HDX experiments have been used to further support the structural characterization of metabolites. The results showed that CP undergoes a series of ligand exchange biotransformation reactions with water and other nucleophiles like thio groups of methionine, cysteine, acetylcysteine, glutathione and thioether. This is the first research approach focused on the structure elucidation of biotransformation products of CP in rats, and the identification of metabolites provides essential information for further pharmacological and clinical studies of CP, and may also be useful to develop various effective new anticancer agents.

Although it has been known that pomegranate (Punica granatum L.) contains several steroid hormones, concrete experimental proofs about that have not been published until now. In order to identify and evaluate the contents of steroid hormones including estrone in pomegranate, we analyzed pomegranate seed, fruit juice and commercial preparations. We developed a reproducible and sensitive method for separation and identification of steroid hormones in pomegranate samples using both high performance liquid chromatography (HPLC)–PDA and gas chromatography (GC)–MS. In case of HPLC, an isocratic elution method using 35% aqueous acetonitrile solution at 1.0 ml/min with photodiode-array (PDA) detection at 225 nm and 254 nm was found to optimally separate and identify the steroid hormones from the pomegranate samples with a run time of less than 30 min. The pomegranate samples were comparatively analyzed to the HPLC results by GC/FID or GC/MS detection on a HP-1 (30 m length, 0.32 mm I.D.) with helium as carrier gas under the oven temperature control as follows: start 220 °C for 5 min, raising 5 °C per min, final 280 °C for 10 min. The HPLC and GC methods were successfully applied to the identification of steroid hormones in pomegranate samples. Our results suggested that there were no steroid estrogens including estrone, estradiol and testosterone in pomegranate seed, fruit juice and preparations. Consequently, we assumed that the previously reported analysts of pomegranate were misunderstood their analytical results according to either the estrogen-like effects or similarity of peak retention time and Rf values in experiments.

A sensitive and rapid liquid chromatography positive ion electrospray ionization tandem mass spectrometric (LC/ESI-MS/MS) method has been developed and validated for the quantitative determination and distribution of cisplatin (CP) in kidney and liver tissues after intravenous administration of drug to adult male Sprague Dawley rats. Oxaliplatin (OXP) was used as an internal standard. The tissue samples were homogenized and extracted using conventional liquid-liquid extraction method with phosphate buffer containing ethyl acetate and then subjected to LC-MS analysis. The chromatographic separation was achieved on an Agilent ZORBAX SB C-18 column (50 × 2.1 mm, 1.8 µm) using the mobile phase consisting of 0.1% formic acid in water (Solvent A) : methanol (Solvent B) (40 : 60; v/v) in an isocratic elution followed by detection with positive ion electrospray ionization tandem mass spectrometry using the transitions of m/z 301 265 for CP and m/z 398 310 for OXP in multiple reaction monitoring mode. The calibration curve was linear in the range of 5.0-7000 and 10.0-6000 ng/ml for kidney and liver tissue homogenates, respectively. The method revealed good performances in terms of within-batch, between-batch precision (1.31-5.70%) and accuracy (97.0-102.24%) for CP in both kidney and liver tissue homogenates including lower and upper limits of quantification. The recoveries from spiked control samples were81.0% and87.0 % for CP and OXP, respectively. Matrix effect was found to be negligible, and the stability data were within the acceptable limits. Further, the validated LC/ES-MS/MS method was successfully applied to investigate the distribution of CP in kidney and liver tissues after intravenous administration of CP to male Sprague Dawley rats. The results showed that the higher amount of CP was distributed in kidney followed by liver, which indicated that CP mainly accumulated in kidney tissues and renal excretion might be a primary and main elimination route. This is the first research approach focused on the quantitative determination and distribution of CP in rat kidney and liver tissue homogenates by using LC/ESI-MS/MS, which could provide essential information for further pharmacological and clinical studies of CP.

To determine whether intra-arterial infusion of triolein emulsion has biochemical and histopathologic effect on rabbit liver.An emulsion of 0.2 mL triolein in 20 mL of saline was infused into either the hepatic arteries of nine rabbits (group 1) or the superior mesenteric arteries of 12 rabbits (group 2). Five rabbits infused with 20 mL of normal saline were used as a control group (group 3). The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to evaluate liver function in each group just before the infusion, at 2 h, day 1, day 4, and day 7 following infusion. Each rabbit in all of the groups was infused with Evans blue on day 7 to evaluate changes in vascular permeability, and obtain the stained area of the hepatic surface. If the stained area was not available, the anteroinferior portion of the right hepatic lobe was selected. The obtained tissues were examined by light, electron and confocal microscopy. The changes in AST and ALT levels at each time point were calculated and statistically analyzed using a mixed linear model. A P value0.05 was regarded as statistically significant.In group 1 (hepatic artery group), both the AST and ALT serum levels increased significantly on day 1 (P = 0.0016 and P0.0001, respectively) compared with the control group, followed by a decrease thereafter. In group 2 (portal vein group), the AST level increased on day 4 (P = 0.0095), while the ALT level increased significantly on day 1 (P0.0001), and decreased thereafter, as compared with the control. For the remainder of the examination days, there were no significant changes in the AST and ALT levels (P0.05). Only three rabbits in each group showed hepatic surface staining with the Evans blue dye. Light and electron microscopic findings showed no specific changes in the selected hepatic tissues. Confocal microscopic examination with transferase-mediated dUTP nick-end labeling stain revealed lack of hepatocyte apoptosis in any of the groups. There were no differences in the results between group 1 and group 2.Infusion of triolein emulsion into rabbit livers revealed a minimal transient decrease of liver function, and no specific histopathologic changes.

Background: Triolein emulsion infusion into the brain produces transiently increased vascular permeability. Objectives: The purpose of this study was to find the minimum percentage of triolein emulsion required for studying vascular permeability with minimal brain edema. Materials and Methods: Sixty healthy cats were divided into six groups according to the concentration of emulsified triolein infused into the carotid artery: group 1, 0.125% (n = 10); group 2, 0.25% (n = 10); group 3, 0.5% (n = 10); group 4, 1% (n = 10); group 5, 2% (n = 10); and group 6, saline infusion (control group, n = 10). T2-, T1- and contrast enhanced T1-weighted MR images were obtained 2 hours after infusing triolein emulsion. Contrast enhancement ratios (CERs) and signal intensity ratios (SIRs) versus contralateral hemispheres were calculated. Statistical analysis was performed by analysis of variance followed by Tukey’s test. P values of ≤ 0.05 were considered significant. Results: The lesion hemispheres showed mild hyperintensity due to edema on T2-weighted images, and contrast enhancement on post-contrast T1-weighted images in cats of group 1-5. CERs showed statistically significant differences between the control group and group 3 (P = 0.006), group 4 (P = 0.003), and group 5 (P < 0.001). However, SIRs were significantly different between the control group and group 5 only (P < 0.001). Conclusion: The minimum concentration of triolein emulsion required to increase vascular permeability adequately with minimal brain edema in a cat model was 0.5%.

In an effort to define the mechanism underlying the host immune downregulation inherent to Trichinella spiralis infection, we compared the levels of Th1, Th2, and regulatory cytokines and CD4(+)CD25(+) forkhead box P3 (FoxP3)(+) T (T(reg)) cell recruitment, as well as cellular pathology in the airway between T. spiralis infected and uninfected asthma-induced mice. After the induction of allergic airway inflammation, we noted influxes of inflammatory cells into the peribronchial tree. However, in the T. spiralis infection groups, cellular infiltration was minimal around the bronchial tree, with only a smattering of inflammatory cells. In the OVA-challenged group after T. spiralis infection, the numbers of macrophages and eosinophils in the bronchial alveolar lavage fluid were reduced by 23% and 52%, respectively, as compared to those of the OVA-challenged group. Airway hyperresponsiveness of OVA-challenged mice after T. spiralis infection was significantly suppressed as compared to the OVA-only challenged mice. The T. spiralis-infected mice exhibited a significant reduction in IL-5 concentrations relative to that noted in the OVA-challenged group (p

Background: Triolein emulsion embolization into the carotid artery depicts reversible increased vascular permeability that can promote the effect of chemotherapy or can reduce the amount of chemotherapeutic drugs for equivalent effectiveness. Purpose: To establish the minimum dosage of 0.5% triolein for studying vascular permeability changes in a triolein emulsion model. Material and Methods: Sixty-six cats were divided into six groups based on the amount of emulsified triolein (0.5%) infused into the carotid artery: group 1 ( n=12, 6 ml/kg), group 2 ( n=12, 4.5 ml/kg), group 3 ( n=12, 3 ml/kg), group 4 ( n=10, 1.5 ml/kg), group 5 ( n=10, 1 ml/kg), and group 6 ( n=10, 3 ml/kg of saline (control group)). T1-weighted, T2-weighted, and post-contrast T1-weighted MRI was performed 2 h after the infusion of the triolein emulsion. Contrast enhancement ratios (CERs) were obtained with pre- and post-contrast T1-weighted images in the ipsilateral and contralateral hemispheres. Signal intensity ratios (SIRs) of the ipsilateral and contralateral hemispheres were evaluated on T2-weighted images. After removal of the brain tissues, edema ratios in the ipsilateral and contralateral hemispheres were obtained from wet versus dry brain weights. Data were statistically evaluated by analysis of variance, followed by the Tukey honestly significant difference test to compare the difference in the mean CER of the ipsilateral and contralateral hemispheres, mean SIR on T2-weighted image, and mean edema ratio between each group when overall significance was attained. Results: In the ipsilateral hemispheres, the difference in the CER between the control group and groups 1 ( P=0.004), 2 ( P=0.043), and 3 ( P=0.008) were statistically significant. The difference in the CERs between the triolein emulsion groups was not statistically significant ( P>0.05). The T2-weighted SIRs were significantly different between the control group and groups 1 ( P=0.027) and 2 ( P=0.004). However, the edema ratios of all doses in the triolein emulsion groups showed no significant differences compared with the control group. Conclusion: The minimum dosage of 0.5% triolein emulsion to achieve increased vascular permeability in the hemisphere in cat brains appears to be 3 ml/kg. This minimum dosage of triolein emulsion can be useful for acquiring basic data in further studies of vascular permeability changes in a triolein emulsion model.

Background To test the hypothesis that triolein emulsion will increase vascular permeability of skeletal muscle. Methods Triolein emulsion was infused into the superficial femoral artery in rabbits (triolein group, n = 12). As a control, saline was infused (saline group, n = 18). Pre- and post-contrast T1-weighted MR images were obtained two hours after infusion. The MR images were qualitatively and quantitatively evaluated by assessing the contrast enhancement of the ipsilateral muscles. Histologic examination was performed in all rabbits. Results The ipsilateral muscles of the rabbits in the triolein group showed contrast enhancement, as opposed to in the ipsilateral muscles of the rabbits in the saline group. The contrast enhancement of the lesions was statistically significant (p < 0.001). Histologic findings showed that most examination areas of the triolein and saline groups had a normal appearance. Conclusion Rabbit thigh muscle revealed significantly increased vascular permeability with triolein emulsion; this was clearly demonstrated on the postcontrast MR images.

Purpose: This study was conducted to generate theoretical constructs on depression from the study data by examining and interpreting Korean housewives’ experience with depression to elicit its meaning, understand it better, and develop empirical knowledge on it. Methods: The data were collected in a community public mental health center between April 1, 2012 and September 30, 2012 using in-depth interviews and theoretical sampling. The participants were 12 women aged 40-64 years who scored 7 or higher in the Korean version of the 21-item Hamilton Rating Scale for Depression (Kim, 1980). Collected data were analyzed by grounded theory methodology using open, axial, selective coding process. Results: It was found that the basic socio-psychological process of Korean housewives' living through depression could be summarized into the following four phases: (1) the vanishing of the self into thin air, (2) becoming an empty shell, and (3) searching for the meaning of life, (4) fulfilling of an empty shell. Conclusion: This study may enhance the culturally elusive understanding of Korean housewives' experience with depression. As they are living through a hollow empty shell which looks normal on the outside, so can’t get support from their families. It's important to educate their families about depressive phases.

In a previous study, we reported our discovery of Acanthamoeba contamination in domestic tap water; in that study, we determined that some Acanthamoeba strains harbor endosymbiotic bacteria, via our molecular characterization by mitochondrial DNA restriction fragment length polymorphism (Mt DNA RFLP). Five (29.4%) among 17 Acanthamoeba isolates contained endosymbionts in their cytoplasm, as demonstrated via orcein staining. In order to estimate their pathogenicity, we conducted a genetic characterization of the endosymbionts in Acanthamoeba isolated from domestic tap water via 16S rDNA sequencing. The endosymbionts of Acanthamoeba sp. KA/WP3 and KA/WP4 evidenced the highest level of similarity, at 97% of the recently published 16S rDNA sequence of the bacterium, Candidatus Amoebophilus asiaticus. The endosymbionts of Acanthamoeba sp. KA/WP8 and KA/WP12 shared a 97% sequence similarity with each other, and were also highly similar to Candidatus Odyssella thessalonicensis, a member of the alpha-proteobacteria. The endosymbiont of Acanthamoeba sp. KA/WP9 exhibits a high degree of similarity (85-95%) with genus Methylophilus, which is not yet known to harbor any endosymbionts. This is the first report, to the best of our knowledge, to show that Methylophilus spp. can live in the cytoplasm of Acanthamoeba.

Objective The purpose of this study is to evaluate the effect of dexamethasone on the damaged blood-ocular barrier caused by triolein emulsion, using contrast-enhanced MR imaging. Materials and Methods An emulsion of 0.1-mL triolein in 20 mL of saline was infused into the carotid arteries of 32 cats, 12 cats were placed in the treatment group and 18 cats were placed in the Control group. Thirty minutes after the infusion of triolein emulsion, a set of orbital pre- and post-contrast T1-weighted MR images (T1WIs) were obtained. Infusion of 10 mg/kg dexamethasone into the ipsilateral carotid artery of each of the cats in the treatment group cats and 20 mL saline in each of the cats in the control group was given. A second set of pre- and post-contrast orbital T1WIs were obtained three hours following triolein emulsion infusion. Qualitative analysis was performed for the the anterior chamber (AC), the posterior chamber (PC), and in the vitreous humor of the ipsilateral and contralateral eyes. The signal intensity ratios of the ipsilateral eye over the contralateral eye were quantitatively evaluated in the three ocular chambers on the first and second set of T1WIs, and were then statistically compared. Results Qualitatively, the AC, the PC or the vitreous did not show immediate contrast enhancement on the first and the second set of post-contrast T1WIs. However, the AC and the PC showed delayed contrast enhancement for both groups of cats on the second pre-contrast T1WIs. No enhancement or minimally delayed enhancement was seen for the vitreous humor. Quantitatively, the signal intensity ratios in the PC of the treatment group of cats were statistically lower than the ratios of the control group of cats for the second set of T1WIs (p = 0.037). The AC and vitreous showed no statistically significant difference between the feline treatment group and control group (p > 0.05). Conclusion Contrast-enhanced MR images revealed increased vascular permeability in the PC of the eye after infusion of triolein emulsion. Dexamethasone seems to decrease the breakdown of the blood-aqueous barrier in the PC.