Development of a Gas Chromatography-Time-of-Flight Method for Detecting Glucosinolate Metabolites and Volatile Organic Compounds in Kimchi.

This study examined the volatile organic compounds (VOCs) and metabolites of glucosinolate (GLS) contained in kimchi and analyzed GLS using myrosinase. The analysis was conducted using gas chromatography-time of flight (GC-TOF), and VOC and the metabolite quantities were detected and analyzed. Based on 22 samples, tests were conducted, and 12 metabolites and 52 VOCs were found. When the detected metabolites were compared in general, the rate of isothiocyanate, which is well known for its anticancer effects and various other activities, was the highest. A total of 52 VOCs, including 15 aliphatic hydrocarbons, 7 acids, and 6 alcohols, were detected by GC-TOF. Therefore, the analytical methods provide a good basis to examine VOC and GLS metabolites; furthermore, the methods are of great help to secure excellent kimchi and evaluate its quality.

Surveillance To Prevent the Spread of Norovirus Outbreak from Asymptomatic Food Handlers during the PyeongChang 2018 Olympics.

ABSTRACT: Human noroviruses are major causes of nonbacterial gastroenteritis and are transmitted by both food and water, as well as person-to-person. Asymptomatic norovirus infection of food handlers may play a role in transmission. The outbreak of norovirus infections was recognized in the PyeongChang Winter Olympics, starting with security staff on 3 February 2018. The Ministry of Food and Drug Safety in the Republic of Korea conducted norovirus surveillance from asymptomatic food handlers of food-catering facilities related to the Olympics to prevent the spread of noroviruses. Rectal swab samples (707) from food handlers were collected and examined for noroviruses by using real-time reverse transcription PCR and conventional reverse transcription PCR. Five of 707 samples were identified as noroviruses. Genotypes of the norovirus-positive samples were determined with sequencing analysis. Identified genotypes of norovirus in asymptomatic food handlers included GI.3, GII.4, and GII.17. The GII.17 strain was prevalent among the genotypes, accounting for three of five detections. Food handlers with noroviruses detected in rectal swabs were excluded from cooking, and all food handled by infected food handlers was discarded. Surveillance of norovirus infection for food handlers contributed to preventing norovirus spread.

Simultaneous determination of synthetic food additives in kimchi by liquid chromatography-electrospray tandem mass spectrometry.

A new analytical method was developed for the simultaneous determination of seven food additives (Ponceau 4R, Allura Red AC, Amaranth, 4-hydroxymethyl benzoic acid, ethyl-4-hydroxybenzoate, butyl-4-hydroxybenzoate, and saccharin sodium) in kimchi using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. The linearity, sensitivity, selectivity, precision, and accuracy of the method were validated. The limit of detection was 0.00004-0.24 µg/mL, and the limit of quantification was 0.00012-0.8 µg/mL. Recoveries ranged from 85.65 to 120.82%. The method was successful and may help to ensure food safety.

Research on the contamination levels of norovirus in food facilities using groundwater in South Korea, 2015-2016.

Norovirus (NoV) is a major pathogenic virus that is responsible for foodborne and waterborne gastroenteritis outbreaks. Groundwater is an important source of drinking water and is used in agriculture and food manufacturing processes. This study investigated norovirus contamination of groundwater treatment systems at 1360 sites in seven metropolitan areas and nine provinces in 2015-2016. Temperature, pH, residual chlorine, and turbidity content were assessed to analyze the water quality. In 2015, six sites were positive for the presence of NoV (0.88%) and in 2016, two sites were positive (0.29%); in total, NoV was detected in 8 of the 1360 sample sites (0.59%) investigated. Identified genotypes of NoV in groundwater included GI.5, 9 and GII.4, 6, 13, 17, and 21. GII.17 was the most prevalent genotype in treated groundwater used in the food industry. This dominance of GII.17 was corroborated by NoV infection outbreak cases and the results of a survey of coastal waters in South Korea in 2014-2015. Although a low detection rate was observed in this study, NoV is a pathogen that can spread extensively. Therefore, it is necessary to periodically monitor levels of norovirus which is responsible for food poisoning in groundwater. This is a first report to reveal epidemic genotype shift of norovirus in groundwater treatment system of food facilities in South Korea. Our results may contribute to the enhancement of public health and sanitary conditions by providing molecular epidemiological information on groundwater NoV.

Reduced P300 amplitude during a visuospatial attention task in idiopathic rapid eye movement sleep behavior disorder.

OBJECTIVES: Idiopathic rapid eye movement sleep behavior disorder (IRBD) patients are prone to cognitive deficits, which include attention, executive, and visuospatial dysfunctions. Even patients with normal cognition may exhibit subclinical electrophysiological dysfunction. This study aimed to evaluate visuospatial attention processing in IRBD patients with normal cognition and to compare their findings with those of age- and sex-matched healthy controls. METHODS: We recorded event-related potentials (ERPs) and performance measures during a variant of the Posner task in 14 IRBD patients and 14 control subjects. Behavioral data and the mean P300 amplitude were compared between groups. RESULTS: No group difference was found for reaction time or accuracy, but a significant group effect was observed for the P300 amplitude. IRBD patients had reduced P300 amplitude (µV) than controls in both valid (IRBD: 0.53 ± 1.05 vs Controls: 1.61 ± 0.95; p = 0.008) and invalid (IRBD: 0.74 ± 0.99 vs Controls: 1.73 ± 0.86; p = 0.009) conditions. The P300 amplitude was correlated with Montreal cognitive assessment (MOCA) scores (r = 0.424, p = 0.024). CONCLUSION: Reduced P300 amplitude during the Posner task provides electrophysiological evidence for subclinical visuospatial attention deficits in cognitively normal IRBD patients. The results of this study imply that cortical dysfunction is already present in patients with IRBD in their early disease stage.

Abnormal Sleep Delta Rhythm and Interregional Phase Synchrony in Patients with Restless Legs Syndrome and Their Reversal by Dopamine Agonist Treatment.

BACKGROUND AND PURPOSE: The purpose of this study was to characterize abnormal cortical activity during sleep in restless legs syndrome (RLS) patients and to determine the effects of treatment with a dopamine agonist. Based on whole-brain electroencephalograms, we attempted to verify alterations in the functional network as well as the spectral power of neural activities during sleep in RLS patients and to determine whether the changes are reversed by treatment with pramipexole. METHODS: Twelve drug-naïve RLS patients participated in the study. Overnight polysomnography was performed before and after treatment: the first recording was made immediately prior to administering the first dose of pramipexole, and the second recording was made 12-16 weeks after commencing pramipexole administration. Sixteen age-matched healthy participants served as a control group. The spectral power and interregional phase synchrony were analyzed in 30-s epochs. The functional characteristics of the cortical network were quantified using graph-theory measures. RESULTS: The delta-band power was significantly increased and the small-world network characteristics in the delta band were disrupted in RLS patients compared to the healthy controls. These abnormalities were successfully treated by dopaminergic medication. The delta-band power was significantly correlated with the RLS severity score in the RLS patients prior to treatment. CONCLUSIONS: Our findings suggest that the spectral and functional network characteristics of neural activities during sleep become abnormal in RLS patients, and these abnormalities can be successfully treated by a dopamine agonist.

Altered Functional Connectivity in Idiopathic Rapid Eye Movement Sleep Behavior Disorder: A Resting-State EEG Study.

Study Objectives: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered as a prodromal stage of synucleinopathy. Although loss of functional connectivity is implicated in neurodegenerative diseases, network characteristics of electroencephalography (EEG) in iRBD are unknown. Therefore, we evaluated resting-state EEG functional connectivity to identify the brain network changes in patients with iRBD. Methods: We prospectively enrolled 20 patients with polysomnography-confirmed iRBD and 16 controls. Four patients with mild cognitive impairment were excluded from the analysis after cognitive function tests. EEG was recorded during relaxed wakefulness. We computed the weighted phase lag index as a measure of functional connectivity from EEG recordings. Results: All patients with iRBD (mean age 64.3 years; men, 68.8%) had no overt manifestations of neurodegenerative diseases such as Parkinsonism or dementia. The mean duration from symptom onset was 4.8 years. Overall connectivity strength did not differ between the two groups in all frequency bands. However, comparisons of each functional connection with the nonparametric permutation test demonstrated iRBD had decreased delta-band functional connectivity in the frontal regions. There were no significantly increased functional connections in all frequencies. The altered connections had a significant correlation with RBD questionnaire scores. Notably, delta-band weighted phase lag index between left frontal and central regions was correlated with verbal fluency performance (r = 0.486, p = .007). Conclusions: Resting-state brain network of iRBD was characterized by a loss of delta-band functional connectivity. Therefore, functional networks in iRBD are altered at the early phase of disease.

Identification and Quantification of Glucosinolates in Kimchi by Liquid Chromatography-Electrospray Tandem Mass Spectrometry.

A novel and simple method for detecting five glucosinolates (glucoalyssin, gluconapin, glucobrassicanapin, glucobrassicin, and 4-methoxyglucobrassicin) in kimchi was developed using liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). The chromatographic peaks of the five glucosinolates were successfully identified by comparing their retention times, mass spectra. The mobile phase was composed of A (acetonitrile) and B (water). As for glucosinolate, the relative quantities were found through sinigrin, and five different compounds that have not been previously discovered in kimchi were observed. Monitoring was carried out on the glucosinolate in 20 kimchis distributed in markets, and this study examined the various quality and quantity compositions of the five components. The glucoalyssin content ranged from 0.00 to 7.07 µmol/g of day weight (DW), with an average content of 0.86 µmol/g of DW, whereas the gluconapin content ranged from 0.00 to 5.85 µmol/g of DW, with an average of 1.17 µmol/g of DW. The content of glucobrassicanapin varied between 0.00 and 11.87 µmol/g of DW (average = 3.03 µmol/g of DW), whereas that of glucobrassicin varied between 0.00 and 0.42 µmol/g of DW (average = 0.06 µmol/g of DW). The 4-methoxyglucobrassicin content ranged from 0.12 to 9.36 µmol/g of DW (average = 3.52 µmol/g of DW). A comparison of the contents revealed that, in most cases, the content of 4-methoxyglucobrassicin was the highest.

Tyrosinase inhibitory components from Aloe vera and their antiviral activity.

A new compound, 9-dihydroxyl-2'-O-(Z)-cinnamoyl-7-methoxy-aloesin (1), and eight known compounds (2-9) were isolated from Aloe vera. Their structures were elucidated using 1D/2D nuclear magnetic resonance and mass spectra. Compound 9 exhibited reversible competitive inhibitory activity against the enzyme tyrosinase, with an IC50 value of 9.8 ± 0.9 µM. A molecular simulation revealed that compound 9 interacts via hydrogen bonding with residues His244, Thr261, and Val283 of tyrosinase. Additionally, compounds 3 and 7 were shown by half-leaf assays to exhibit inhibitory activity towards Pepper mild mottle virus.

Identification of six new lupane-type triterpenoids from Acanthopanax koreanum leaves and their tyrosinase inhibitory activities.

Chemical investigation of Acanthopanax koreanum leaves resulted in the isolation of 13 compounds (1-13), including six new (20,29)-dehydrolupane-type triterpenoids: 3α,11α,30-trihydroxylup-20(29)-en-23,28-dioic acid (1), 3α,11α,30-trihydroxylup-20(29)-en-28-oic acid (2), 3α,11α,30-trihydroxylup-23-al-20(29)-en-28-oic acid (3), 3α, 11α-dihydroxy-20-oxo-30-norlupane-23,28-dioic acid (5), (20S)-3α-hydroxy-30 oxolupane-23,28-dioic acid (8), (20S)-3ß,7ß,29-trihydroxy-lupane-23-al-28-oic acid (10), and one novel compound isolated for the first time, named 3α,20α,29-trihydroxylupane-23,28-dioic acid (9), together with six known compounds (4, 6, 7, and 11-13). Chemical structures of the isolated compounds were evaluated by analyzing and comparing spectroscopic data with those reported in the literature. These compounds were also evaluated for their tyrosinase inhibitory effects. Among them, compounds 3, 7, 9, and 12 showed significant inhibitory effects, with inhibitory concentrations of 50% (IC50) values ranging from 8.61 to 63.5 µM.

Development of an immunoaffinity chromatography and HPLC-UV method for determination of 16 sulfonamides in feed.

A novel and simple method for detecting 16 sulfonamides (SAs) in animal feed using high performance liquid chromatography equipped with a photo-diode array detector (HPLC/PDA) and immunoaffinity chromatography was developed. The chromatographic peaks of the 16 SAs were successfully identified by comparing their retention times and UV spectra with reference standards. Method validation was performed with linearity, sensitivity, selectivity, accuracy and precision. The limits of detection (LODs) for the instrument used to study sulfonamides ranged from 14.1 to 45.0 µg/kg, and the limits of quantification (LOQs) ranged from 46.9 to 150.0 µg/kg. Average recoveries of the 16 SAs ranged from 78.2% to 105.2%. Method replication resulted in intraday and interday peak area variation of <5.5%. The developed method was specific and reliable and is suited for the routine analysis of SAs in animal feed.

Simultaneous determination of 15 phenolic compounds and caffeine in teas and mate using RP-HPLC/UV detection: method development and optimization of extraction process.

A reversed-phase high performance liquid chromatographic coupled to ultraviolet detection (RP-HPLC/UV) method was developed for simultaneous determination of 15 phenolic compounds and caffeine in TEAS (green tea, oolong tea, black tea and mate). Furthermore, the extraction process of total phenolic contents (TPC) from TEAS were optimized using response surface methodology (RSM) based on a central composite design (CCD) and then applied to extraction of TEAS. The best conditions obtained using the model were as follow: green tea--extraction time of 123 min, extraction temperature of 70 °C and ethanol concentration of 75%, oolong tea--extraction time of 98 min, extraction temperature of 70 °C and ethanol concentration of 69%, black tea--extraction time of 105 min, extraction temperature of 71 °C and ethanol concentration of 63%, and mate--extraction time of 103 min, extraction temperature of 71 °C and ethanol concentration of 61%. Among the extraction methods used in this study, heat-reflux extraction was found to result in the highest values of TPC. The chromatographic peaks of the 16 studied compounds were successfully identified by comparing their retention time and UV spectra with the reference standards. Method validation was performed by means of linearity, sensitivity, selectivity, accuracy and precision. The developed method was found to be simple, specific and reliable and is suited for routine analysis of phenolic compounds and caffeine in TEAS.

A New HPLC-ELSD Method for Simultaneous Determination of N-Acetylglucosamine and N-Acetylgalactosamine in Dairy Foods.

A rapid high performance liquid chromatographic method with evaporative light scattering detection (HPLC-ELSD), using a carbohydrate column, was developed for simultaneous determination of N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) in dairy foods. Sample preparation was performed by precipitation using acetonitrile. The limits of detection were 2.097 mg/L for GlcNAc and 3.247 mg/L for GalNAc. The limits of quantification were 6.043 mg/L for GlcNAc and 9.125 mg/L for GalNAc. Accuracy ranged from 96.4 to 105.7% for GlcNAc and from 97.1 to 104.1% for GalNAc. The precision of the method was <1.7% for GlcNAc and <2.2% for GalNAc. The mean recovery of the method was measured by spiking samples with 30.0-120.0 mg/L GlcNAc or 12.5-50.0 mg/L GalNAc and was found to be 95.1-105.5% for GlcNAc and 99.5-105.9% for GalNAc. The stability test results of standard solutions stored at 4, 20, and 40°C were 96.2-104.7% for GlcNAc and 98.0-106.5% for GalNAc. This study determined GlcNAc and GalNAc in dairy foods using HPLC-ELSD method. This rapid, simultaneous quantitation method might be useful as a mean of convenient quality control of dairy foods.

In vivo and in vitro evaluation of Cy5.5 conjugated epidermal growth factor receptor binding peptide.

The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor and plays an important role in carcinogenesis. In this study, the epidermal growth factor receptor binding peptide (EGBP) was identified using a phage display method and evaluated in U87MG cells in order to investigate the possibility to target the EGFR using an optical imaging system. Cyanine dye 5.5 (Cy5.5) was conjugated with EGBP-GGG-SC, EGBP-AOC-SC, and EGBP-AM2BA-SC. Cellular binding study of EGBP-Linker-Cy5.5 conjugates or (125)I-EGBP-Linker compounds was performed in U87MG cells. Optical imaging studies were performed in U87MG bearing mice. Three of seven clones from the 12-mer peptide library showed a specific binding affinity to rhEGFR, and they encoded the same 12 amino acid peptide sequence, FPMFNHWEQWPP. Confocal images show that the fluorescent signal of EGBP-Linker-Cy5.5 conjugates was decreased in the order: EGBP-AOC-Cy5.5≫EGBP-AM2BA-Cy5.5>EGBP-GGG-Cy5.5. EGBP-AOC-Cy5.5 appeared in cell cytoplasm and surface, and it was inhibited by free EGBP apparently. The cellular binding of EGBP-AOC-Cy5.5 exhibited a higher average radiance value than EGBP-GGG-Cy5.5 and EGBP-AM2BA-Cy5.5. Among various (125)I-EGBP-Linker compounds, EGBP-GGG showed a higher binding than other compounds. However, uptake of (125)I-EGBP-AOC was clearly inhibited by free EGBP in inhibition study. In an in vivo study, the fluorescent signal of EGBP-AOC-Cy5.5 treated mouse was mainly detected in the tumor and kidney. Among the three derivatives, EGBP-AOC-Cy5.5 was the optimized optical imaging agent for U87MG EGFR positive tumors in the animal model. This study demonstrated the EGBP-Linker-Cy5.5 conjugates may be useful as a potential EGFR target optical probe.

Optical imaging of MMP expression and cancer progression in an inflammation-induced colon cancer model.

The purpose of this study was to use a near-infrared (NIR) fluorescent cyclic His-Try-Gly-Phe peptide to characterize and image the expressions of matrix metalloproteinases (MMPs), which are correlated with cancer promotion, in an inflammation-induced colorectal cancer (ICRC) model. We explored the relationship between the development of colon cancer and the expression of MMPs at the same colonic sites in ICRC models. To develop ICRC models, mice were administered a single intraperitoneal dose (10 mg/kg) of azoxymethane (AOM) and exposed orally to 2% dextran sodium sulfate (DSS) for one week. MMP-2 expression and ß-catenin activation in colonic lesions were characterized by immunohistochemical (IHC) staining. After being treated with inducers for some time, cancerous lesions were found to express high ß-catenin and MMP-2. The profiles of MMP expression were correlated with ß-catenin activation in the colonic lesions. c(KAHWGFTLD)NH(2) (C6) peptide was prepared by standard Fmoc peptide synthesis to target MMPs. Molecular weight of Cy5.5-C6 was 1,954.78 g/mol (calculated MW = 1955.23 g/mol). The in vitro characterization of Cy5.5-C6 showed MMP binding specificity in a cell experiment. In vivo NIRF imaging showed high accumulation of Cy5.5-C6 in tumors with associated expression of MMP-2 in colonic lesions after intravenous injection. The MMP-2 specificity of Cy5.5-C6 was confirmed by successful inhibition of probe uptake in the tumor due to the presence of excess C6 peptide. The use of Cy5.5-C6 to target MMP-2 has the potential to be developed into an effective molecular imaging agent to monitor ICRC progress.

Dextran-conjugated vascular endothelial growth factor receptor antibody for in vivo melanoma xenografted mouse imaging.

Intact immunoglobulin G antibody has a relatively large molecule size of approximately 150 kDa that remains in the bloodstream for many weeks, which is a considerable disadvantage when it is used to carry radioactive materials for imaging. To lower background activity and increase the contrast of images, we investigated antivascular endothelial growth factor (VEGF) receptor 2 antibody (DC101) conjugated dextran for VEGF receptor 2 imaging in tumor xenografted mice. DTPA-conjugated aminodextran was synthesized, reacted with sulfo-LC-SPDP, and then reacted with DC101. The binding affinity of DTPA-dextran-DC101 to Flk-1 was measured. The gamma imaging and biodistributions of (99m)Tc-DTPA-dextran-DC101, (99m)Tc-DTPA-DC101, and (125)I-DC101 were studied in B16F10 melanoma xenografted mice. The dissociation values for DC101, DTPA-DC101, and DTPA-dextran-DC101 were 22.48, 3.05, and 14.74 pM, respectively. In gamma images, (99m)Tc-DTPA-dextran-DC101 showed weak liver uptake and rapid kidney elimination. In biodistribution results, the liver uptake of (99m)Tc-DTPA-dextran-DC101 was similar with that of (99m)Tc-DTPA-DC101 at each time point. However, the blood activity of (99m)Tc-DTPA-dextran-DC101 has shown significant differences, compared with (99m)Tc-DTPA-DC101 at all time points. The tumor accumulation of dextran-conjugated antibody was increased with time, whereas that of dextran nonconjugated antibody decreased. In particular, the pattern of tumor uptake of (99m)Tc-DTPA-dextran-DC101 was similar to that of (125)I-DC101, so this was thought to reflect the kinetics of DC101, unlike the nonconjugated form. The results of this study suggested that introduction of dextran moiety to make (99m)Tc-radiolabeled DC101 imaging agent could provide better images with the impaired background and the steady increasing binding to the receptor. However, further studies are necessary to improve clinical pharmacokinetics, such as enhancement of tumor uptake and impaired renal uptake.

A case of malignant migrating partial seizures in infancy as a continuum of infantile epileptic encephalopathy.

The syndrome of malignant migrating partial seizures in infancy (MMPSI) is characterized by onset before the age of 6 months, nearly continuous electrographic seizures involving multiple independent areas of onset in both hemispheres, and poor developmental outcome. This report presents a case involving a patient with MMPSI, who later developed West syndrome. At the age of 2 months old, he showed multifocal partial seizures, which were refractory to antiepileptic drugs. His electroencephalogram (EEG) revealed characteristic migrating multifocal epileptiform activities and neuroimaging finding was normal. The focal seizures were refractory to antiepileptic drugs and ketogenic diet. When he was 9 months old, epilepic spasms were observed with hypsarrhythmia on EEG. He also showed severe developmental delay. MMPSI may be a continuum of infantile epileptic encephalpathy and could evolve to West syndrome.

Effect of molecular imaging on validation of developed anti-hVEGFR2 therapeutic antibody.

Vascular endothelial growth factor receptor type 2 (VEGFR2)-targeted tumor treatment is an antiangiogenic therapeutic strategy. The human sodium iodide symporter (hNIS) gene is a useful reporter gene for tumor imaging and radiotherapy. In this study, we investigated the evaluation of therapeutic efficacy in hNIS gene-transfected tumor xenografts using a gamma imaging system after treatment with an anti-VEGFR2 antibody. Human breast cancer MDA-MB-231 cells transfected with the hNIS gene were injected subcutaneously into the right flanks of BALB/c nude mice. Therapy was initiated when the tumor volume reached approximately 130-180 mm(3). The animals were intravenously injected with 50, 100, or 150 µg of antibody every 3 days for 16 days. Gamma imaging was performed 1 and 2 weeks after the first injection to monitor the effects of tumor therapy. Mice were sacrificed 2 weeks after the first injection of antibody and the tumors were removed for CD31 staining and reverse transcription-polymerase chain reaction (RT-PCR) assay. All groups of mice that were treated with anti-hVEGFR2 antibody showed markedly reduced tumor growth compared to control mice. In vivo gamma imaging results showed that, at 1 week after the first injection of the anti-hVEGFR2 antibody, (125)I uptake of a tumor treated with 150 µg of antibody was 24.5% lower than that in the controls. At 2 weeks, (125)I uptake in the tumor treated with 150 µg of antibody was as low as 44.3% of that in the controls. CD31 staining and RT-PCR assays showed that blood vessel formation and expression of the hNIS gene were reduced with increased treatment doses. This study demonstrated the feasibility of molecular imaging and the therapeutic efficacy of developing therapeutic antibody anti-hVEGFR2 using a gamma imaging system in hNIS gene-transfected tumor xenograft mice.

Iodine 125-labeled mesenchymal-epithelial transition factor binding peptide-click-cRGDyk heterodimer for glioma imaging.

In our previous study, mesenchymal-epithelial transition factor (c-Met)-binding peptides (cMBP) had been readily radiolabeled with radioactive iodide for glioma imaging because of five histidine amino acids. However, iodinated cMBP showed relatively unfavorable in vivo kinetics. For this reason, we tried to design dual peptide ligands that would be advantageous in recognizing both c-Met receptor and integrin α(v) ß(3) . A cMBP-click-cRGDyk (cyclic Arg-Gly-Asp-Tyr-Lys) heterodimer was synthesized from mini polyethylene glycol-conjugated cMBP-3 glycine (GGG)-a single name of amino acids (SC) (Ser-Cys) and cRGDyk through a click (1 + 3 cycloaddition), and then labeled with iodine 125 (I-125) via histidine in the cMBP and tyrosine in the cRGDyk. The receptor-binding characteristics and tumor-targeting efficacy of cMBP-click-cRGDyk were tested in vitro and in vivo. A cMBP-click-cRGDyk had comparable integrin α(v) ß(3) -binding affinity with cRGDyk. The results of the biodistribution of (125) I-cMBP-click-cRGDyk at 4 h showed higher tumor-to-blood, tumor-to-liver, and tumor-to-muscle ratios: 10.07, 6.76, and 11.12, compared to 2.34, 1.99, and 5.18 of (125) I-cMBP-GGG-SC, respectively. U87MG tumor xenografts could be visualized by single photon emission computed tomography (SPECT)/CT using (125) I-cMBP-click-cRGDyk and also image contrast and overall quality were improved compared to (125) I-cMBP-GGG-SC. As the results of in vivo inhibition using free cRGDyk or cMBP-GGG-SC indicated, the tumoral uptake of (125) I-cMBP-click-cRGDyk decreased. This finding means that (125) I-cMBP-click-cRGDyk was specifically uptaken by integrin α(v) ß(3) and the c-Met receptor. Although imaging quality was improved, additional experiments are needed to acquire significant image-quality improvement.

Neuropsychological status of children with newly diagnosed idiopathic childhood epilepsy.

We characterized the neuropsychological status of children with newly diagnosed idiopathic childhood epilepsy and measured differences in IQ between children with different types of epilepsy. The Korean Education Development Institute-Wechsler Intelligence Scale for Children (KEDI-WISC) was administered to 72 patients (35 males and 37 females), of mean age 8.7±2.6 years, with newly diagnosed idiopathic childhood epilepsy. Of these patients, 22 (30.6%) had generalized epilepsy, 48 (66.7%) localization-related epilepsy, and 2 (2.8%) mixed epilepsy. Children with generalized epilepsy and benign childhood epilepsy with centro-temporal spikes (BCECTS) were of similar verbal IQ and full-scale IQ, although performance IQ was significantly lower in patients with generalized epilepsy. Among children with BCECTS, those with unilateral spikes had higher full-scale and performance IQ scores than those with bilateral spikes. Follow-up studies on large numbers of patients are needed to determine the effects of epilepsy per se, and antiepileptic drugs, on intelligence.