Pesticide residues in vegetables and risk assessment for consumers in Korea during 2010-2014.

This study was carried out to assess the exposure to pesticide residues from vegetable consumption of residents in Seoul using data on pesticide residue concentrations and the quantity of vegetables consumed. A total of 34,520 samples of 96 types of vegetables collected from 2010 to 2014 by the Seoul Metropolitan Government Institute of Health and Environment (SIHE) were analysed for 283 different pesticide residues. Among the vegetable samples, 86.1% did not contain any measurable levels of pesticide and 1.4% had residues exceeding Maximum Residue Limits (MRL). A total of 105 different pesticide residues were found and 45 residues exceeded MRLs. The most commonly found residues were azoxystrobin, diethofencarb, procymidone, cypermethrin, and tebufenpyrad. A total of 547 vegetable samples from 37 different types of vegetables had residues exceeding MRLs. From these results, 20 agrochemicals were chosen based on their high level of detection and violation rate of the MRL. The potential health risk associated with exposure to the pesticides through vegetable intake was estimated as a Risk Index (RI, %ADI). For a citizen of Seoul, the RIs of the mean value and 97.5th percentile were shown to be 0.0 ~ 7.4% and 0.4 ~ 73.9% respectively. For citizens of Seoul by age (consumers only), the highest RIs for children (under 6 years old) and the elderly (over 65 years old) were with chlorothalonil, and the estimated daily intakes (EDI) were 56.0%, 112.5%, respectively, of its ADI. For adults (19 ~ 64 years old) the highest RI was for chlorfenapyr and the EDI reached 118.6%. These results show that, despite the high levels of some pesticide residues, they may not be considered as a serious public health problem.

Monitoring and risk assessment of pesticide residues in commercially dried vegetables.

We tested for residual pesticide levels in dried vegetables in Seoul, Korea. A total of 100 samples of 13 different types of agricultural products were analyzed by a gas chromatography-nitrogen phosphate detector (GC-NPD), an electron capture detector (GC-µECD), a mass spectrometry detector (GC-MSD), and a high performance liquid chromatography-ultraviolet detector (HPLC-UV). We used multi-analysis methods to analyze for 253 different pesticide types. Among the selected agricultural products, residual pesticides were detected in 11 samples, of which 2 samples (2.0%) exceeded the Korea Maximum Residue limits (MRLs). We detected pesticide residue in 6 of 9 analyzed dried pepper leaves and 1 sample exceeded the Korea MRLs. Data obtained were then used for estimating the potential health risks associated with the exposures to these pesticides. The estimated daily intakes (EDIs) range from 0.1% of the acceptable daily intake (ADI) for bifenthrin to 8.4% of the ADI for cadusafos. The most critical commodity is cadusafos in chwinamul, contributing 8.4% to the hazard index (HI). This results show that the detected pesticides could not be considered a serious public health problem. Nevertheless, an investigation into continuous monitoring is recommended.

Long-term immunogenicity of influenza vaccine among the elderly: Risk factors for poor immune response and persistence.

The elderly have been considered as the priority group for influenza vaccination, but their influenza vaccine-induced antibody was believed to decline more rapidly. Long-term immunogenicity of the influenza vaccine among the elderly was evaluated as compared to young adults. Serum hemagglutinin inhibition (HI) titers were determined at pre- and post-vaccination periods (at 1, 6, and 12 months after vaccination). Of the 1018 subjects, 716 (70.3%) were followed up during a 12-month period. Seroprotection rates at 1 month post-vaccination ranged from 70.1% to 90.3% depending on the age group and influenza vaccine virus strain. At 6 months post-vaccination, seroprotection rates for all three strains had declined significantly in adults >or=65 years (P<0.01), but still met the EMEA criteria. Low pre-vaccination HI titer (<1:40) and advanced age were associated with early decline of HI titers, falling below seroprotective levels around 6 months after vaccination.

Dose sparing strategy with intradermal influenza vaccination in patients with solid cancer.

Influenza vaccine is considered to reduce influenza-related morbidity and mortality in patients with underlying chronic medical conditions. Because of fear of vaccine shortage during an influenza pandemic, several antigen sparing strategies have been investigated. The immunogenicity of intradermal influenza vaccination with one half the antigenic contents was compared to that of conventional intramuscular vaccination in patients with solid cancer, and adverse events were assessed after vaccination. There was no significant difference between the injection routes in the hemagglutinin inhibition (HI) response and increase in the titer of A/H1N1, A/H3N2, and B 4-6 weeks after the vaccination; seroconversion factors increased by more than 2.5-fold. Seroresponse rates were more than 40% and seroprotection rates were above 70% against all three influenza strains irrespective of the vaccination routes. No serious events were observed, and local skin reactions were more frequent in the intradermal injection recipients than in the intramuscular recipients (32.7% vs. 9.1%). This study shows that intradermal injection of one half the dose of a commercial influenza vaccine elicits immune responses comparable to those elicited by a full dose of intramuscular vaccine among cancer patients, and it can be tolerated without serious adverse reactions.

Functional expression of recombinant human ribonuclease/angiogenin inhibitor in stably transformed Drosophila melanogaster S2 cells.

A recombinant plasmid harboring heterologous genes coding human ribonuclease/angiogenin inhibitor (RAI) was expressed in stably transformed Drosophila melanogaster Schneider 2 (S2) cells. Stably transformed polyclonal cell populations expressing RAI were isolated after 4 weeks of selection with hygromycin B. Recombinant RAI with a molecular weight of 50 kDa was detected in the intracellular (cell) and extracellular (medium) fractions of S2 cells. Recombinant RAI was purified from the extracellular fraction using a two-step purification scheme comprised of Ni-NTA and ion-exchange chromatography. Purified RAI migrated on SDS-PAGE as a single band in the elution fraction containing 300 mM NaCl. The ribonuclease inhibitor activity of purified RAI was measured using yeast tRNA and RNase A. Purified RAI exhibited an activity of approximately 8 U mug(-1) for the inhibition of RNA degradation by RNase A. Cultivation of stably transformed S2 cells using HyQ((R))SFX-insect MP medium increased cell growth by 79% and approximately doubled the production of recombinant RAI.

Characteristics of non-typhoidal Salmonella isolates from human and broiler-chickens in southwestern Seoul, Korea.

Non-typhoidal Salmonella (NTS) is an important commensal microorganism. The purpose of this study was to determine the epidemiological relation between NTS isolates from livestock and NTS isolates from human by analyzing antimicrobial susceptibilities and performing molecular typing. We determined the serotypes of 36 human clinical isolates and 64 livestock isolates, performed antimicrobial susceptibility testing against 8 antibiotics, and determined the molecular types of isolated NTS spp. by pulsed field gel electrophoresis (PFGE). In human isolates, S. enteritidis was the most common serotype (17 isolates; 47.2%) and S. typhimurium the second most (8 isolates; 22.2%). In livestock isolates, S. typhimurium was the most common serotype (15 isolates; 23.44%), and S. enteritidis was the second most (14 isolates; 21.88%). Ampicillin and tetracycline resistance were 50% (32/64 isolates) each among broiler-chicken NTS isolates. No human or livestock NTS isolates showed resistance to ciprofloxacin, TMP-SMX, or ceftriaxone. However, 19.4% (7/36) and 46.8% (30/64) of the human and livestock NTS isolates were resistant to nalidixic acid (MIC > or = 16 mg/mL), respectively. The presence of the three identical PFGE molecular types from human and broiler-chicken NTS isolates suggests the possibility of transmission from livestock to humans.

Clinical impact of influenza immunization in patients with liver cirrhosis.

BACKGROUND: Influenza vaccine is considered to reduce influenza-related morbidity and mortality in patients with underlying chronic medical conditions. Yet in liver cirrhosis, influenza vaccines have received little attention in determining the potential benefits. OBJECTIVES: We intended to evaluate the clinical benefits of influenza vaccination and clinical outcomes of influenza in patients with liver cirrhosis. METHODS: We performed a controlled, prospective clinical trial of 311 cirrhotic patients, who were enrolled in October 2004. Among them, 198 patients were vaccinated with a trivalent influenza vaccine and the rest were not vaccinated. Both groups were followed with respect to the occurrence of influenza-like illness (ILI) until May 2005. RESULTS: Overall incidences of ILI (p=0.064) and culture positivity of influenza (p=0.009) were remarkably higher in unvaccinated group compared to the vaccinated group. Most of the cirrhotic patients with influenza had fever (91.6%) and complained of myalgia (83.3%) without respiratory symptoms, which were not typical clinical presentations of influenza. Influenza vaccination also decreased influenza-related complication rates in patients with liver cirrhosis. CONCLUSION: Influenza vaccination should be recommended to all cirrhotic patients. High suspicion is required for early diagnosis and antiviral treatment, allowing for the frequent hepatic decompensation among cirrhotic patients.

In vitro activities of carbapenem/sulbactam combination, colistin, colistin/rifampicin combination and tigecycline against carbapenem-resistant Acinetobacter baumannii.

OBJECTIVES: To determine the in vitro activities and interactions of imipenem, colistin and tigecycline with old antibacterial agents against carbapenem-resistant Acinetobacter baumannii. METHODS: Forty-three carbapenem-resistant A. baumannii isolates from the intensive care unit of a university hospital were collected and their MICs of imipenem, colistin and tigecycline were determined. With eight randomly selected carbapenem-resistant isolates, an in vitro time-kill study was performed for the evaluation of antibacterial activity of colistin, tigecycline, imipenem/sulbactam and colistin/rifampicin. RESULTS: The time-kill study of colistin demonstrated bactericidal activity against A. baumannii at concentrations of 4xMIC and 8xMIC, whereas tigecycline showed bacteriostatic activity at all concentrations. The combination regimens of imipenem/sulbactam and colistin/rifampicin were synergistic and bactericidal at 1xMIC. CONCLUSIONS: Imipenem/sulbactam combination, colistin and tigecycline showed good in vitro activities against carbapenem-resistant A. baumannii isolates. Even though colistin is bactericidal against carbapenem-resistant A. baumannii, the colistin/rifampicin combination is more warranted in order to be certain.

Radiolabeled high affinity peptidomimetic antagonist selectively targets alpha(v)beta(3) receptor-positive tumor in mice.

OBJECTIVES: The aim of this research was to synthesize radiolabeled peptidomimetic integrin alpha(v)beta(3) antagonists that selectively target integrin alpha(v)beta(3) receptor and clear rapidly from the whole body. METHODS: Integrin alpha(v)beta(3) antagonists, 4-[2-(3,4,5,6-tetrahydropyrimidine-2-ylamino)ethyloxy]benzoyl-2-(S)-aminoethylsulfonyl-amino-beta-alanine (IA) and 4-[2-(3,4,5,6-tetrahydro-pyrimidin-2-ylamino)-ethyloxy]benzoyl-2-(S)-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonylamino-beta-alanine hydrochloride (IAC), a hydrophobic carbamate derivative of IA, were conjugated with 2-p-isothiocyanatobenzyl-DOTA at the amino terminus and labeled with (111)In. The (111)In labeled IA and IAC were subjected to in vitro receptor binding, biodistribution and imaging studies using nude mice bearing the receptor-positive M21 human melanoma xenografts. RESULTS: The (111)In-labeled IA (40%) and -IAC (72%) specifically bound in vitro to alpha(v)beta(3) (0.8 microM) at a molar excess. This receptor binding was completely blocked by a molar excess of cold IA to alpha(v)beta(3). The higher receptor-binding affinity of the (111)In-labeled IAC was reflected in higher tumor uptake and retention: 5.6+/-1.4 and 4.5+/-0.7 %ID/g vs. 3.8+/-0.9 and 2.0+/-0.3 %ID/g for the (111)In-labeled IA at 0.33 and 2 h. The tumor uptakes were inhibited by the co-injection of 200 microg of IA, indicating that the uptake was receptor mediated. These antagonists were excreted primarily via the renal system. The (111)In activity retained in the whole body was quite comparable between the (111)In-labeled IA (24% ID) and the (111)In-labeled IAC (33% ID) at 2 h. The higher peak tumor uptake and longer retention resulted in higher tumor-to-background ratios for the (111)In-labeled IAC at 2 h with 9.7, 2.3, 0.8, 1.9, 7.1, 2.2, 0.9, 3.7 and 9.9 for blood, liver, kidney, lung, heart, stomach, intestine, bone and muscle, respectively. The imaging studies with the (111)In-labeled IAC also clearly visualized the receptor-positive tumor at 4 h. CONCLUSIONS: The (111)In-labeled IAC showed an improve tumor targeting kinetics with rapid accumulation and prolonged retention in the alpha(v)beta(3) receptor-positive tumor. This together with the rapid whole-body clearance pharmacokinetics warrants further studies on this IAC analog for molecular imaging of tumor-induced angiogenic vessels and various malignant human tumors expressing the receptor.

Use of antibody as carrier of oligomers of peptidomimetic alphavbeta3 antagonist to target tumor-induced neovasculature.

Sulfhydryl selective reactions were explored to conjugate oligomers of a peptidomimetic integrin alphavbeta3 antagonist, 4-[2-(3,4,5,6-tetrahydropyrimidine-2-ylamino)ethyloxy]benzoyl-2-(S)-aminoethylsulfonylamino-beta-alanine (IA) to monoclonal antibody (MoAb) to increase integrin alphavbeta3 receptor-binding avidity. To generate sulfhydryl groups, N-succinimidyl-S-acetylthioacetate (SATA) was conjugated to both MoAb and IA. Sulfhydryl groups were then generated upon the deacetylation of the protecting acetyl group from the S-acetylthioacetato (ATA) moiety of MoAb-(ATA)n or IA-ATA with 0.02 M hydroxylamine in the presence of 1 mM EDTA at pH 7.2. The major focus was on optimizing the reaction concentrations, molar ratios, and reaction pH to conjugate high levels of IA-(A-SH) to MoAb-(A-SH)n without causing the inter- and intramolecular cross-linking of MoAb. Stepwise reactions of MoAb-(A-SH)n (15 microM MoAb) with a homobifunctional cross-linker, 1,8-bis(maleimido)diethylene glycol (BM[PEO]2) at a >50x molar excess to the -SH, followed by the reaction of the purified product MoAb-(A-S-succinimidomaleimido-[PEO]2)n with IA-(A-SH) at pH 7.2 afforded monomeric MoAb-(A-S-succinimido-[PEO]2-succinimido-S-A-IA)n with <10% high molecular weight oligomeric MoAb. Monomeric MoAb-(A-S-S-[PEO]2-S-S-A-IA)10 (MoAb-IA10) radiolabeled with 111In using 2-(p-isothiocyanatobenzyl)cyclohexyl-DTPA and with 125I using the Iodogen method showed >70% bindability to 0.4 microM alphavbeta3. When injected iv to nude mice with the receptor-positive M21 tumor, MoAb-IA10 radiolabeled with both 111In and 125I accumulated rapidly and was retained in the tumor for a 44 h period while the radioactivity cleared rapidly from the blood, thereby resulting in increasing tumor-to-blood ratios over time. The tumor uptake was similar between the 125I label and the 111In label for a 44 h period. In contrast, the blood radioactivity was lower, but liver and other organ uptakes were much higher for the 111In label than for the 125I. The 111In label produced higher tumor-to-blood ratios but much lower tumor-to-organ ratios than the 125I. The rapid blood clearance, a short peak tumor uptake time, and a low peak tumor uptake value with prolonged tumor retention of this macromolecule appear to support a hypothesis that MoAb-IA10 primarily binds to alphavbeta3 receptors on angiogenic vessels, but not on the tumor. This hypothesis was substantiated by the fluorescence microscopic analysis of FITC-MoAb-IA10, which showed that FITC-MoAb-IA10 outlined neovasculatures but not tumor cells at 4 and 21 h ex vivo. Additional proof was observed when blood vessels outlined with rhodamine-lectin, which specifically binds to blood vessels, were superimposable on neovasculatures outlined with FITC-MoAb-IA10.

Prevalence and molecular epidemiology of vancomycin-resistant enterococci (VRE) strains isolated from animals and humans in Korea.

BACKGROUND: To assess the possibility of VRE transmission from animals to humans, we studied the prevalence of vancomycin-resistant enterococci (VRE) in farm animals, raw chicken meat, and healthy people. We then determined the molecular relatedness of VRE isolates between animals and humans in Korea. METHODS: We aimed to isolate VRE from 150 enterococci specimens of farm animals, 15 raw chicken meat samples, and stools from 200 healthy people. Species differentiation was done with conventional biochemical tests. Vancomycin resistance genotyping was done by polymerase chain reaction (PCR). Using the agar dilution method, antimicrobial susceptibility was tested for 8 antimicrobials and pulsed-field gel electrophoresis (PFGE) was done to evaluate the molecular relatedness of VRE isolates. RESULTS: The prevalence of VRE was 14.7% (22/150) in farm animal specimens, 1% (2/200) in healthy people, and 60% (9/15) in raw chicken meat. Of 22 animal VRE isolates, 1 vanA E. faecium, 15 vanC1 E. gallinarum, and 6 vanC2 E. casseliflavus were identified. All of the 9 VRE from raw chicken meat and all of the 20 clinical VRE strains were vanA E. faecium. However, in healthy people, only 2 vanC2 E. casseliflavus were isolated. These showed low-level resistance to vancomycin and susceptibility to teicoplanin. However, 9 VRE strains from raw chicken meat had high-level resistance to vancomycin (MIC(50,90): >128 microg/mL), teicoplanin (MIC(50,90): >128 microg/mL), ampicillin (MIC(50,90): >128 nicrog/mL), erythromycin (MIC(50.90): >128 microg/mL), and tetracycline (MIC(50/90): 128/>128 microg/mL). CONCLUSION: This study demonstrated little evidence of VRE colonization in healthy people despite high recovery of VRE among raw chicken meat. It is suggested that there is little evidence of VRE transmission from animals to healthy people. However, we assumed that there exists the possibility of VRE contamination during the processing of chicken meat.

Emergence of vanA Genotype Vancomycin-Resistant Enterococci with Low or Moderate Levels of Teicoplanin Resistance in Korea.

In Korea, vancomycin-resistant enterococci have become important nosocomial pathogens since the late 1990s, and most vancomycin-resistant enterococcal isolates have been VanA phenotype-vanA genotype strains. In 2001, we experienced an outbreak of VanB phenotype-vanA genotype vancomycin-resistant enterococci at a university hospital. This is the first report of VanB-vanA vancomycin-resistant enterococci from humans in Korea.