• The Korean Journal of Pain
• /
• v.24 no.4
• /
• pp.221-225
• /
• 2011

Hyaluronidase is an enzyme that has temporary and reversible enzymatic effects on the matrix of connective tissue. When added to local anesthetics in pain treatments, it enhances their infiltration and dispersal into tissues. It is widely used in anesthesia for ocular, dental, and plastic surgery. Reports of drug hypersensitivity to hyaluronidase are rare and are usually confined to peribulbar or retrobulbar anesthesia during ophthalmic surgery. However, few reports exist on adverse drug reaction after epidural injection. We have observed two patients experiencing anaphylactic shock caused by hyaluronidase following epidural injection. Most of the patients with a hypersensitivity to hyaluronidase had one previous uneventful injection containing hyaluronidase, implying that sensitization had taken place. However, hypersensitivity occurring at the first administration is possible. A positive skin test can help establish the diagnosis. Although rare, the possibility of an allergic reaction to hyaluronidase should be considered even in patients with no known previous exposure.

• Biomolecules & Therapeutics
• /
• v.10 no.4
• /
• pp.274-280
• /
• 2002

The fluoroquinolones have been reported to cause, although at low frequency, severe phototoxicity which is due to singlet oxygen produced by ultraviolet-A (UVA; 320-400 nm) exposure. The objective of this study was to evaluate the phototoxicity based on plasma and tissue concentrations of commonly prescribed fluoroquinolones; lomefloxacin (LFLX), enoxacin (ENX), ofloxacin (OFLX), and ciprofloxacin (CPFX). The phototoxic potentials were investigated by measuring increments in ear thickness, 24 hrs after these fluoroquinolones were orally administered to Balb/c mice, which they were exposed to UVA 17.5 J/$\textrm{cm}^2$ for 2 hrs following drug administration. The fifty percent ear thickness increment-inducing doses ($ETID_{50}$), determined by single ascending dosing of each fluoroquinolone to mice, were calculated to be 50(LMFX), 250(ENX), 770(OFLX), 1100(CPFX) mg/kg. Post the administration of ETID$_{50}$, drug concentrations in plasma and ear tissue were measured at specified times and phototoxicities were quantified. Both peak plasma ($\mu\textrm{g}$/ml) and ear tissue ($\mu\textrm{g}$/g) concentrations were summarized as follows; 7.3/1.4 for LMFX, 15.0/1.6 for ENX, 90.1/18.4 for OFLX and 87.2/3.7 for CPFX. The degree of photo toxicity was more relevant to plasma concentrations than tissue concentrations. In order to assess the effect of irradiation time after drug administration on phototoxicity, the 2 hr UVA irradiation was given at 0, 1, 2, 3, and 5 hr after administering $ETID_{50}$, respectively and photo toxicities were evaluated. The shorter inteval between dosing and UVA exposure was, the higher risk of phototoxicity was produced.d.

• Journal of Food Hygiene and Safety
• /
• v.27 no.4
• /
• pp.388-394
• /
• 2012

The present study was carried out to assess the dietary exposure and the risk for arsenic (As) and mercury (Hg) through mushrooms intake. Various samples (n = 536) covering 17 kinds of mushrooms were collected from retail outlets and markets in Korea. The contents of As were 0.003 (King oyster) ~ 1.952 (Matsutake) mg/kg in raw mushrooms and 0.015 (Fuscoporia obliqua) ~ 16.95 (Matsutake) mg/kg in dry mushrooms, respectively. The contents of Hg were 0.001 (King oyster) ~ 0.030 (Matsutake) mg/kg in raw mushrooms and 0.004 (Oyster) ~ 0.588 (Matsutake) mg/kg in dry mushrooms, respectively. The mean dietary exposures of As was $0.151{\mu}g$/day, taking 0.005% of provisional tolerable weekly intake (PTWI). The mean dietary exposures of Hg was $0.022{\mu}g$/day, corresponding to 0.071% of PTWI. Therefore, the level of overall dietary exposure to As and Hg for Korean population through mushroom was far below the levels recommended by Joint FAO/WHO Expert Committee on Food Additivies, indicating little possibility of concern.

• Toxicological Research
• /
• v.30 no.1
• /
• pp.39-44
• /
• 2014

Bisphenol A (BPA) is widely used in the production of polycarbonate plastics, epoxy resins, and food and beverage containers. In the present study, we aimed to investigate the relationship between urinary concentrations of BPA and waist circumference in Korean adults. A total of 1,030 Korean adults (mean age, $44.3{\pm}14.6$ years) were enrolled in the study on the integrated exposure to hazardous materials for safety control, conducted by the Ministry of Food and Drug Safety from 2010 to 2012. Abdominal obesity was defined as having a waist circumference of at least 90 cm and 85 cm for men and women, respectively. The participants were divided into 4 groups according to the urinary BPA concentration quartile. Waist circumference was significantly higher among subjects with a urinary BPA concentration in the highest quartile relative to those in the lowest quartile (p = 0.0071). Linear regression analysis revealed a significant positive association between urinary BPA concentrations and body mass index, body fat, after adjusting for potential confounders. Moreover, subjects with urinary BPA concentrations in the fourth quartile were more likely to be obese compared to those with urinary BPA concentrations in the first quartile (odds ratio, 1.938; 95% CI: 1.314~2.857; p for trend = 0.0106). These findings provide evidence for a positive association between urinary BPA concentration and waist circumference in Korean adults.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.15
• /
• pp.6513-6519
• /
• 2015

Background: Recent attention on chemotherapeutic intervention against cancer has been focused on discovering and developing phytochemicals as anticancer agents with improved efficacy, low drug resistance and toxicity, low cost and limited adverse side effects. In this study, we investigated the effects of Curcuma C20-dialdehyde on growth, apoptosis and cell cycle arrest in colon and cervical cancer cell lines. Materials and Methods: Antiproliferative, apoptosis induction, and cell cycle arrest activities of Curcuma C20-dialdehyde were determined by WST cell proliferation assay, flow cytometric Alexa fluor 488-annexin V/propidium iodide (PI) staining and PI staining, respectively. Results: Curcuma C20 dialdehyde suppressed the proliferation of HCT116, HT29 and HeLa cells, with IC50 values of $65.4{\pm}1.74{\mu}g/ml$, $58.4{\pm}5.20{\mu}g/ml$ and $72.0{\pm}0.03{\mu}g/ml$, respectively, with 72 h exposure. Flow cytometric analysis revealed that percentages of early apoptotic cells increased in a dose-dependent manner upon exposure to Curcuma C20-dialdehyde. Furthermore, exposure to lower concentrations of this compound significantly induced cell cycle arrest at G1 phase for both HCT116 and HT29 cells, while higher concentrations increased sub-G1 populations. However, the concentrations used in this study could not induce cell cycle arrest but rather induced apoptotic cell death in HeLa cells. Conclusions: Our findings suggest that the phytochemical Curcuma C20-dialdehyde may be a potential antineoplastic agent for colon and cervical cancer chemotherapy and/or chemoprevention. Further studies are needed to characterize the drug target or mode of action of the Curcuma C20-dialdehyde as an anticancer agent.

• Molecular & Cellular Toxicology
• /
• v.3 no.2
• /
• pp.98-106
• /
• 2007

Genotoxic stress triggers a variety of biological responses including the transcriptional activation of genes regulating DNA repair, cell survival and cell death. In this study, we investigated to examine gene expression profiles and genotoxic response in TK6 cells treated with DNA damaging agents MNNG (N-methyl-N'-nitrosoguanidine) and hydrogen peroxide $(H_2O_2)$. We extracted total RNA in three independent experiments and hybridized cRNA probes with oligo DNA chip (Applied Biosystems Human Genome Survey Microarray). We analyzed raw signal data with R program and AVADIS software and identified a number of deregulated genes with more than 1.5 log-scale fold change and statistical significancy. We indentified 14 genes including G protein alpha 12 showing deregulation by MNNG. The deregulated genes by MNNG represent the biological pathway regarding MAP kinase signaling pathway. Hydrogen peroxide altered 188 genes including sulfiredoxins. These results show that MNNG and $H_2O_2$ have both uniquely regulated genes that provide the potential to serve as biomarkers of exposure to DNA damaging agents.

• Korean Journal of Clinical Pharmacy
• /
• v.28 no.3
• /
• pp.174-180
• /
• 2018

Objective: Clostridium difficile Infection (CDI) is one of the common nosocomial infections. As elderly population increases, the proper treatment has been emphasized. We investigated the risk factors associated with CDI unimprovement in elderly patients. Furthermore, we performed drug use evaluation of old CDI patients and oldest-old CDI patients. Methods: It was a retrospective study using electronic medical record at Kangbuk Samsung Medical Center (KBSMC) from January 2016 to December 2017. Seventy three patients aged 65 years or older, diagnosed with CDI by Clostridium difficile Toxin B Gene [Xpert] were screened and they were assessed for risk factors regarding unimprovement status. We also evaluated drug use evaluation in old patients ($65{\leq}age$<80) and oldest-old patients ($80{\leq}age$) by assessing the use of initial therapy, severity, dose, route, treatment course, days of use, total days of use and treatment outcome of initial therapy. Results: Out of 73 patients aged over 65 years, four patients were excluded because they did not receive any treatment. There were 31 improved patients and 38 unimproved patients after initial therapy. We were able to find out patients with surgical comorbidity or endocrine comorbidity (especially, diabetes mellitus) had 2.885 more risk of becoming unimproved than those patients without surgical comorbidity or endocrine comorbidity. Drug use evaluation for CDI was generally fair, but vancomycin as initial therapy is more recommended than metronidazole. Conclusion: Although age, antibiotics exposure, use of antacids are all important risk factors for CDI, our result did not show statistical significance for these risk factors. However, the study is meaningful because the number of elderly population keeps increasing and recently updated guideline suggests the use of vancomycin as drug of choice for CDI.

• Analytical Science and Technology
• /
• v.23 no.6
• /
• pp.595-606
• /
• 2010

A total 221 samples of the retailed foods collected from 2004 to 2007 was examined to estimate the level of dioxins(29 congeners) by the isotopic dilution method, and the exposure of population of Korean to dietary of dioxins was performed. Dioxins levels were calculated using TEF values established in 1998 and 2005, respectively. The average levels (pg TEQ/g) were less than 0.01 for polished rice, 0.04 (poultry)-0.13 (beef) for meats, 0.04 (milk)-0.05(cheese) for milk and dairy products, 0.13 for egg (york, only) and 0.11 (alaska pollack)-1.35 (pacific mackerel) for fishes. The estimated daily intake of Korean through foods was 0.47 pg TEQ/kg bw/day, and it was estimated as about 11% to tolerable daily intake (TDI; 4 pg TEQ/kg bw/day) of Korea and Japan. Consequently, it was concluded that there was no health risk.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.17
• /
• pp.7195-7200
• /
• 2014

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

• Genomics & Informatics
• /
• v.16 no.3
• /
• pp.52-58
• /
• 2018

In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p < 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials.