Disinfectants including polyhexamethylene guanidine phosphate (PHMG) and mixtures of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) have been widely used in Korea to prevent microbial growth in the humidifier water, which triggered an outbreak of serious respiratory diseases. In addition to the respiratory syndrome, disease-related symptoms including liver toxicity, asthma, and skin allergies were also found after extensive survey of people exposed to the humidifier disinfectants (HDs). In this study, eye irritation tests were performed based on the Organization for economic co-operation and development (OECD) test guidelines 492 using EpiOcular™ which is a tissue model of reconstructed human cornea-like epithelium. As results, the raw materials of PHMG (26% as active ingredient) and CMIT/MIT (1.5% as active ingredient) were classified under UN globally harmonized system of classification and labeling of chemical (GHS) category 1 or category 2. However, aqueous dilutions of raw materials such as market products of HDs that contain 0.13% of PHMG and 0.03% of CMIT/MIT or further dilutions of the market products for humidifier that contain 0.0013% of PHMG and 0.0003% of CMIT/MIT were classified under any category, which suggested absence of eye irritation at the test concentration.
Asthma ; Classification ; Disinfectants ; Epithelium ; Guanidine ; Humans ; Humidifiers ; Hypersensitivity ; Korea ; Liver ; Skin ; United Nations ; Water

Disinfectants including polyhexamethylene guanidine phosphate (PHMG) and mixtures of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) have been widely used in Korea to prevent microbial growth in the humidifier water, which triggered an outbreak of serious respiratory diseases. In addition to the respiratory syndrome, disease-related symptoms including liver toxicity, asthma, and skin allergies were also found after extensive survey of people exposed to the humidifier disinfectants (HDs). In this study, eye irritation tests were performed based on the Organization for economic co-operation and development (OECD) test guidelines 492 using EpiOcular™ which is a tissue model of reconstructed human cornea-like epithelium. As results, the raw materials of PHMG (26% as active ingredient) and CMIT/MIT (1.5% as active ingredient) were classified under UN globally harmonized system of classification and labeling of chemical (GHS) category 1 or category 2. However, aqueous dilutions of raw materials such as market products of HDs that contain 0.13% of PHMG and 0.03% of CMIT/MIT or further dilutions of the market products for humidifier that contain 0.0013% of PHMG and 0.0003% of CMIT/MIT were classified under any category, which suggested absence of eye irritation at the test concentration.
Asthma ; Classification ; Disinfectants ; Epithelium ; Guanidine ; Humans ; Humidifiers ; Hypersensitivity ; Korea ; Liver ; Skin ; United Nations ; Water

The biological activity of particles is largely dependent on their size in biological systems. Dispersion in the aqueous phase has been both a critical impediment to and a prerequisite for particle studies. Carbon black has been used as a surrogate to investigate the biological effects of carbonaceous particles. Here, biocompatible methods were established to disperse carbon black into ultrafine and fine particles which are generally distinguished by the small size of 100 nm. Carbon black with a distinct particle size, N330 and N990 were suspended in blood plasma, cell culture media, Krebs-Ringer's solution (KR), or physiological salt solution (PSS). Large clumps were observed in all dispersion preparations; however, sonication improved dispersion - averaged particle sizes for N330 and N990 were 85.0 +/- 42.9 and 112.4 +/- 67.9 nm, respectively, in plasma; the corresponding sizes in culture media were 84.8 +/- 38.4 and 164.1 +/- 77.8 nm. However, sonication was not enough to disperse N330 less than 100 nm in either KR or PSS. Application of Tween 80 along with sonication reduced the size of N330 to less than 100 nm, and dispersed N990 larger than 100 nm (73.6 +/- 28.8 and 80.1 +/- 30.0 nm for N330 and 349.5 +/- 161.8 and 399.8 +/- 181.1 nm for N990 in KR and PSS, respectively). In contrast, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) exhibited little effect. Electron microscopy confirmed the typical aciniform structure of the carbon arrays; however, zeta potential measurement failed to explain the dispersibility of carbon black. The methods established in this study could disperse carbon black into ultrafine and fine particles, and may serve as a useful model for the study of particle toxicity, particularly size-related effects.
1,2-Dipalmitoylphosphatidylcholine ; Carbon ; Cell Culture Techniques ; Culture Media ; Microscopy, Electron ; Particle Size ; Plasma ; Polysorbates ; Silicones ; Sonication ; Soot

An analysis of patients and fatalities due to exposure to polyhexamethylene guanidine (PHMG) shows that PHMG causes mainly lung diseases such as pulmonary fibrosis. However, no research on the other organs has been conducted on this matter yet. So, an in-depth discussion on toxicological techniques is needed to determine whether or not PHMG is toxic to organs other than just the lungs. For the test of target organ toxicity by PHMG exposure, a toxicokinetic study must first be conducted. However, measurement method for PHMG injected into the body has not yet been established because it is not easy to analyze polymer PHMG, so related base studies on analytical technique for PHMG including radio-labeling chemistry must come first. Moreover, research on exposure-biomarker and effect-biomarker must also be conducted, primarily related to clinical application. Several limitations seem to be expected to apply the biomarker study to the patient because much time has passed after exposure to the humidifier disinfectant. It is why a more comprehensive toxicological researches must be introduced to the causality for the victims.
Chemistry ; Guanidine ; Humans ; Humidifiers* ; Lung ; Lung Diseases ; Methods ; Polymers ; Pulmonary Fibrosis

OBJECTIVES: Hepatotoxicity of acetaminophen has been widely studied. However, the adverse effects on the heart have not been sufficiently evaluated. This study was performed to investigate cytotoxicity and alterations of gene expression in cultured cardiomyocytes (H9C2 cells) after exposure to acetaminophen. METHODS: H9C2 cells were incubated in a 10 mM concentration of acetaminophen for the designated times (6, 12, and 24 hours), and cytotoxicity was determined by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Alteration of gene expression was observed by microarray analysis, and RT-PCR was performed for the three representative oxidative stress-related genes at 24 hours after treatment. RESULTS: It revealed that acetaminophen was toxic to cardiomyocytes, and numerous critical genes were affected. Induced genes included those associated with oxidative stress, DNA damage, and apoptosis. Repressed genes included those associated with cell proliferation, myocardial contraction, and cell shape control. CONCLUSIONS: These findings provide the evidences of acetaminophen-induced cytotoxicity and changes in gene expression in cultured cardiomyocytes of H9C2 cells.
Acetaminophen ; Apoptosis ; Benzeneacetamides ; Cell Proliferation ; Cell Shape ; DNA Damage ; Gene Expression ; Heart ; Microarray Analysis ; Myocardial Contraction ; Myocytes, Cardiac ; Oxidative Stress ; Piperidones

OBJECTIVES: Effects of nanoparticles including zinc oxide nanoparticles, titanium oxide nanoparticles, and their mixtures on skin corrosion and irritation were investigated by using in vitro 3D human skin models (KeraSkin(TM)) and the results were compared to those of an in vivo animal test. METHODS: Skin models were incubated with nanoparticles for a definite time period and cell viability was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide method. Skin corrosion and irritation were identified by the decreased viability based on the pre-determined threshold. RESULTS: Cell viability after exposure to nanomaterial was not decreased to the pre-determined threshold level, which was 15% after 60 minutes exposure in corrosion test and 50% after 45 minutes exposure in the irritation test. IL-1alpha release and histopathological findings support the results of cell viability test. In vivo test using rabbits also showed non-corrosive and non-irritant results. CONCLUSIONS: The findings provide the evidence that zinc oxide nanoparticles, titanium oxide nanoparticles and their mixture are 'non corrosive' and 'non-irritant' to the human skin by a globally harmonized classification system. In vivo test using animals can be replaced by an alternative in vitro test.
Animals ; Cell Survival ; Classification ; Corrosion* ; Humans ; Nanoparticles* ; Nanostructures ; Rabbits ; Skin* ; Titanium ; Zinc Oxide

Disinfectants including polyhexamethylene guanidine phosphate (PHMG) and mixtures of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) have been widely used in Korea to prevent microbial growth in the humidifier water, which triggered an outbreak of serious respiratory diseases. In addition to the respiratory syndrome, disease-related symptoms including liver toxicity, asthma, and skin allergies were also found after extensive survey of people exposed to the humidifier disinfectants (HDs). In this study, eye irritation tests were performed based on the Organization for economic co-operation and development (OECD) test guidelines 492 using EpiOcularâ„¢ which is a tissue model of reconstructed human cornea-like epithelium. As results, the raw materials of PHMG (26% as active ingredient) and CMIT/MIT (1.5% as active ingredient) were classified under UN globally harmonized system of classification and labeling of chemical (GHS) category 1 or category 2. However, aqueous dilutions of raw materials such as market products of HDs that contain 0.13% of PHMG and 0.03% of CMIT/MIT or further dilutions of the market products for humidifier that contain 0.0013% of PHMG and 0.0003% of CMIT/MIT were classified under any category, which suggested absence of eye irritation at the test concentration.

BACKGROUNDS/AIMS: We present our experience of laparoscopic liver resection for various liver diseases. METHODS: From April 2008 to August 2012 in Chungnam National University, 68 of 253 liver resections were performed laparoscopically. During the first year, laparoscopy-assisted liver resection was mainly performed and subsequently totally laparoscopic liver resection was the main operative type. Surgery type for treatment purposes was decided preoperatively. Clinical data were collected retrospectively and analyzed. RESULTS: Preoperatively, 43 patients (63.2%) were diagnosed with benign disease, 19 patients (27.9%) were malignant liver tumors and 6 patients (8.8%) were indeterminate liver tumor but favorable towards malignancy. Anatomical major liver resection was performed in 58 cases (85.3%) and 10 cases (14.7%) were non-anatomical resection. Left hemihepatectomy was performed in 38 cases (55.8%) followed by left lateral sectionectomy in 18 cases (26.5%), and segment IV and IVa segmentectomy, were each in 1 case. Mean operation time was 235.0 minutes (range, 60-470) and 14 patients (18.6%) had intraoperative transfusion. Mean postoperative hospital stay was 10.2 days (range, 4-32). Mean operation time of laparoscopy-assisted left lobectomy was 317 minutes and totally laparoscopic left lobectomy was 281 minutes, but there was no significant statistical difference between these two operation types. There were 11 episodes of postoperative complications in 8 patients. There was no mortality after laparoscopic liver resection. CONCLUSIONS: We concluded that laparoscopic liver resection is a feasible operation, but needs to be carefully conducted in malignant tumors.
Chungcheongnam-do ; Humans ; Laparoscopy ; Length of Stay ; Liver Diseases* ; Liver* ; Mastectomy, Segmental ; Mortality ; Postoperative Complications ; Retrospective Studies

Silver nanoparticles (size: 7.9 +/- 0.95 nm, dosage: 250 mg/kg) were orally administered to pregnant rats. At 4 days after parturition, four pups were randomly selected (one pup from one dam) and silver level in liver, kidney, lung and brain was determined by ICP-MS and electron microscope. As results, silver nanoparticles highly accumulated in the tissues of the pups. Silver level in the treated group was 132.4 +/- 43.9 ng/g in the kidney (12.3 fold compared to control group), 37.3 +/- 11.3 ng/g in the liver (7.9 fold), 42.0 +/- 8.6 ng/g in the lung (5.9 fold), and 31.1 +/- 4.3 ng/g in the brain (5.4 fold). This result suggested that the possible transfer of silver nanoparticles from pregnant dams to the fetus through mainly placenta.
Animals ; Brain ; Electrons ; Fetus ; Kidney ; Liver ; Lung ; Nanoparticles ; Parturition ; Placenta ; Rats ; Silver

PURPOSE: Toxicity caused by acetaminophen and its toxic mechanisms in the liver have been widely studied, including effects involving metabolism and oxidative stress. However, its adverse effects on heart have not been sufficiently investigated. This study evaluated the cardiac influence and molecular events occurring within the myocardium in rats treated with a dose of acetaminophen large enough to induce conventional liver damage. MATERIALS AND METHODS: Male rats were orally administered a single dose of acetaminophen at 1,000 mg/kg-body weight, and subsequently examined for conventional toxicological parameters and for gene expression alterations to both the heart and liver 24 hours after administration. RESULTS: Following treatment, serum biochemical parameters including aspartate aminotransferase and alanine aminotransferase were elevated. Histopathological alterations of necrosis were observed in the liver, but not in the heart. However, alterations in gene expression were observed in both the liver and heart 24 hours after dosing. Transcriptional profiling revealed that acetaminophen changed the expression of genes implicated in oxidative stress, inflammatory processes, and apoptosis in the heart as well as in the liver. The numbers of up-regulated and down-regulated genes in the heart were 271 and 81, respectively, based on a two-fold criterion. CONCLUSION: The induced expression of genes implicated in oxidative stress and inflammatory processes in the myocardium reflects molecular levels of injury caused by acetaminophen (APAP), which could not be identified by conventional histopathology.
Acetaminophen/*toxicity ; Administration, Oral ; Analgesics, Non-Narcotic/*toxicity ; Animals ; Drug-Induced Liver Injury/pathology/*physiopathology ; Gene Expression Profiling ; Heart/*physiology ; Liver/pathology/physiology ; Male ; Myocardium/pathology ; Rats ; Transcriptome/*drug effects