Toxicokinetics of zinc oxide nanoparticles (ZnONP) was studied in rats via a single intravenous (iv) injection and a single oral administration (3 mg/kg or 30 mg/kg), respectively. Blood concentrations of zinc (Zn) were monitored for 7 d and tissue distribution were determined in liver, kidneys, lung, spleen, thymus, brain, and testes. To ascertain the excretion of ZnONP, Zn levels in urine and feces were measured for 7 d. ZnONP were not readily absorbed from the gastrointestinal tract (GIT) after oral administration and were excreted mostly in feces. When the nanoparticles were injected iv to rats at a dose of 30 mg/kg, peak concentration appeared at 5 min but returned to normal range by d 2 (48 h after injection). ZnONP were distributed mainly to liver, kidneys, lung, and spleen, but not to thymus, brain, and testes. The distribution level was significantly decreased to normal by d 7. Feces excretion levels after iv injection supported biliary excretion of ZnONP. In rats injected iv with 30 mg/kg, mitotic figures in hepatocytes were significantly increased and multifocal acute injuries with dark brown pigment were noted in lungs, while no significant damage was observed in rats treated orally with the same dosage.

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Effects of nanoparticles (NPs) on skin corrosion and irritation using three-dimensional human skin models were investigated based on the test guidelines of Organization for Economic Co-operation and Development (OECD TG431 and TG439). EpiDermTM skin was incubated with NPs including those harboring iron (FeNPs), aluminum oxide (AlNPs), titanium oxide (TNPs), and silver (AgNPs) for a defined time according to the test guidelines. Cell viabilities of EpiDermTM skins were measured by the 3-(4, 5-dimethylthi-azol-2-yl)-2.5-diphenyltetrazolium bromide based method. FeNPs, AlNPs, TNPs, and AgNPs were non-corrosive because the viability was more than 50% after 3 min exposure and more than 15% after 60 min exposure, which are the non-corrosive criteria. All NPs were also non-irritants, based on viability exceeding 50% after 60 min exposure and 42 hr post-incubation. Release of interleukin 1-alpha and histopathological analysis supported the cell viability results. These findings suggest that FeNPs, AlNPs, TNPs, and AgNPs are ‘non-corrosive’ and ‘non-irritant’ to human skin by a globally harmonized classification system.

We examined whether alterations in vascular endothelial function and early structural changes in atherosclerosis are associated with microvascular complications in patients with type 1 diabetes mellitus (DM). Flow-mediated dilation (FMD) of the brachial artery and carotid intima-media thickness (IMT) measurement were performed in 70 young adults (aged 19 to 35 yr), 48 with type 1 DM, and 22 normal controls. Patients with diabetes had a lower peak FMD response (7.8±3.9 vs. 11.1±1.9%, p<0.001) and increased IMT (0.51±0.10 vs. 0.42±0.07 mm, p<0.001) compared with controls. Twenty (41.7%) of the patients had microvascular complications including neuropathy, nephropathy, or retinopathy. In these complicated diabetic patients, we found a lower FMD response (6.1±2.5 vs. 9.9±3.5%, p=0.001) compared with diabetics without microvascular complications. The presence of microvascular complications was also associated with older age and longer duration of the disease. However, no differences were observed in IMT, body size, blood pressure, HbA1c, C-reactive protein, low-density lipoprotein or high-density lipoprotein cholesterol levels between complicated and non-complicated patients. Endothelial dysfunction and early structural atherosclerotic changes are common manifestations in type 1 DM, and endothelial dysfunction is thought to be an early event in the atherosclerotic process and important in the pathogenesis of microvascular complications.

Recent toxicity studies of zinc oxide nanoparticles by oral administration showed relatively low toxicity, which may be resulted from low bioavailability. So, the intrinsic toxicity of zinc oxide nanoparticles needs to be evaluated in the target organs by intravenous injection for full systemic concentration of the administered dosage. Although the exposure chance of injection route is low compared to oral and/or inhalation route, it is important to see the toxicity with different exposure routes to get better risk management tool. In this study, the effects of zinc oxide nanoparticles on dams and fetuses were investigated in rats after intravenous injection (5, 10, and 20 mg/kg) from gestation day 6 to 20. Two of 20 dams in the 20 mg/kg treatment group died during the treatment period. Hematological examination and serum biochemistry showed dose-dependent toxicity in treated dams. Histopathological analysis of treated dams revealed multifocal mixed cell infiltration and thrombosis in lung, tubular dilation in kidneys, and extramedullary hemopoiesis in liver. Total dead fetuses (post-implantation loss) were increased and the body weight of fetus was decreased in the 20 mg/kg treatment group. Statistical differences in corpora lutea, resorption, placental weight, morphological alterations including external, visceral and skeletal malformations were not observed in treated groups. Based on the data, lowest observed adverse effect level of injection route was suggested to be 5 mg/kg in dams and no observed adverse effect level was suggested to be 10 mg/kg in fetal developmental toxicity.

The purpose of this study was to analyze left ventricular (LV) torsion and untwisting, and to evaluate the correlation between torsion and other components of LV contraction in children with dilated cardiomyopathy (DCM). Segmental and global rotation, rotational rate (Vrot) were measured at three levels of LV using the two-dimensional (2D) speckle tracking imaging (STI) method in 10 DCM patients (range 0.6-15 yr, median 6.5 yr, 3 females) and 17 age- and sex-matched normal controls. Global torsion was decreased in DCM (peak global torsion; 10.9±4.6° vs. 0.3±2.1°, p<0.001). Loss of LV torsion occurred mainly by the diminution of counterclockwise apical rotation and was augmented by somewhat less reduction in clockwise basal rotation. In DCM, the normal counterclockwise apical rotation was not observed, and the apical rotation about the central axis was clockwise or slightly counterclockwise (peak apical rotation; 5.9±4.1° vs. -0.9±3.1°, p<0.001). Systolic counterclockwise Vrot and early diastolic clockwise Vrot at the apical level were decreased or abolished. In DCM, decreased systolic torsion and loss of early diastolic recoil contribute to LV systolic and diastolic dysfunction. The STI method may facilitate the serial evaluation of the LV torsional behavior in clinical settings and give new biomechanical concepts for better management of patients with DCM.

ObjectivesHepatotoxicity 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.MethodsH9C2 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.ResultsIt 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.ConclusionsThese findings provide the evidences of acetaminophen-induced cytotoxicity and changes in gene expression in cultured cardiomyocytes of H9C2 cells.

Rationale: Diabetic ketoacidosis (DKA) can cause several complications. Among them, cardiac complications are the most fatal and difficult to detect. Cardiac markers are prognostic factors for morbidity and mortality in adult patients with DKA. But, there have been very few discussed cases in pediatrics. We report a case of severe DKA in child with elevated cardiac enzymes and prolonged QT interval. Patient concerns: A 12-year-old girl admitted by nausea, vomiting, and lethargy for 1 day. Diagnoses: Her blood sugar level was initially undetectable by the capillary blood glucose meter, and blood gas analysis showed severe DKA with elevated cardiac enzymes and prolonged QT interval. Interventions: The patient was admitted to hospital and intensive intravenous fluid and regular insulin infusion were administered. Outcomes: After 5 days of supportive care, the patient was fully recovered, discharged, and followed up in an outpatient clinic. Lessons: Since the relationship between DKA and myocardial injury has not been clearly elucidated, pediatricians and emergency physicians should remain careful throughout the recovery time as it can lead to life-threatening conditions in various courses.