Biodistribution and in vivo efficacy of genetically modified human mesenchymal stem cells systemically transplanted into a mouse bone fracture model.

Human mesenchymal stem cells (hMSCs) have generated a great deal of interest in clinical application due to their ability to undergo multi-lineage differentiation. Recently, ex vivo genetic modification of hMSCs was attempted to increase their differentiation potential. The present study was conducted to evaluate the biodistribution and in vivo efficacy of genetically modified hMSCs.

Transferability of a modified embryonic stem cell test using a new endpoint for developmental neurotoxicity.

We developed and analyzed a new surrogate endpoint of the mouse embryonic stem cell test (EST) for developmental neurotoxicity. To determine the sensitivity, specificity, and transferability of the new endpoint, a pre-validation team from three independent laboratories optimized and standardized the protocol for neuronal differentiation of mouse embryonic stem cells (mESCs) by measuring the neuronal differentiation rates of mESCs under different culture conditions, such as the presence or absence of basic fibroblast growth factor (bFGF) in the growth media and varying lengths of culture. In addition, a component ratio of neuronal cells was measured by using flow cytometry analysis of β-III tubulin (Tuj1)-positive cells and real-time polymerase chain reaction analysis of microtubule-associated protein 2 (MAP2) mRNA.

Signal detection of methylphenidate by comparing a spontaneous reporting database with a claims database.

Data mining is critical for signal detection in pharmacovigilance systems. In this study, we compared signals between spontaneous reporting data and health insurance claims data for a socially issued drug, methylphenidate. We implemented data-mining tools for signal detection in both databases: Reporting Odds Ratios (ROR), Proportional Reporting Ratios (PRR), Chi-squared test, and Information Component (IC), in addition to a Relative Risk (RR) tool in the claims database.

Assessment of heavy metal exposure via the intake of oriental medicines in Korea.

Oriental medical herbs are mainly natural products that are generated by simple processes, and therefore there is the possibility of contamination with various pollutants, including heavy metals. Heavy metals produce adverse effects in humans, and the toxicities of lead (Pb) and cadmium (Cd) are well established. This study evaluated the effects of exposure to Pb and Cd via the intake of the frequent prescriptions of oriental medicines, and assessed the risk to the Korean population based on domestic data.

Deleterious effects of silymarin on the expression of genes controlling endothelial nitric oxide synthase activity in carbon tetrachloride-treated rat livers.

Aims: Defects in intrahepatic nitric oxide (NO) are attributed to reduced blood flow due to portal hypertension caused by diminished endothelial NO synthase (eNOS) activity. The aim of this study is to identify the therapeutic effects of silymarin on eNOS/NO-related enzymes and hepatic enzymes in carbon tetrachloride (CCl4)-induced cirrhotic rats.

Main Methods: CCl4 treated for 12 weeks was discontinued and then administrated with silymarin daily for 4 weeks.

Safety assessment of chromium by exposure from cosmetic products.

Low level impurities often reside in cosmetic products. The aim of the present study was to estimate the human exposure to chromium from cosmetic products purchased at a local market in South Korea, and to assess the risk on public health. Hexavalent chromium is an impurity substance that contaminates cosmetic products during manufacture.

Toxicity value for 3-monochloropropane-1,2-diol using a benchmark dose methodology.

3-Monochloropropane-1,2-diol (alpha-chlorohydrin, 3-MCPD) is a well-known contaminant that has been detected in a wide range of foods, and that is principally generated in foods prepared by hydrochloric acid hydrolysis, such as acid-hydrolyzed vegetable protein (acid-HVP). 3-MCPD is nephrotoxic to animals at high doses and induced tumors in some organs in both sexes of rodents. NITR have recently reported on the carcinogenicity of 3-MCPD in SD rats that were exposed for 2 years to drinking water.

Effects and regulation of osteopontin in rat hepatic stellate cells.

Using a cDNA microarray, we identified osteopontin (OPN) as one of the genes upregulated in cultured activated hepatic stellate cells (HSCs). Northern and western blot analyses showed that OPN was increasingly expressed during the progressive activation of cultured rat HSCs, and a significant increase in OPN was observed in carbon tetrachloride-induced rat liver fibrosis. In biliary atresia, OPN protein was predominantly expressed in Kupffer cells and HSCs in the necrotic areas.

In vitro pharmacodynamics of CKD-602 in HT-29 cells.

CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) is a recently-developed synthetic camptothecin analogue and currently under clinical development by Chong Kun Dang Pharm (Seoul, Korea). CKD-602 showed potent topoisomerase inhibitory activity in vitro and broad antitumor activity against various human tumor cells in vitro and in vivo in animal models. This study describes the pharmacodynamics of the immediate and delayed cytotoxicity induced by CKD-602 in a human colorectal adenocarcinoma cell line, HT-29, and its intracellular drug accumulation by HPLC.

Methamphetamine-induced apoptosis in a CNS-derived catecholaminergic cell line.

Methamphetamine (METH) causes neurotoxic damages to the dopaminergic system in mammals, but whether it exerts toxicity to dopamine cells in culture has not been fully explored. In order to develop an in vitro model of METH-induced dopamine neurotoxicity toward more systemical examination of the mechanism, we investigated METH toxicity in a clonal dopamine producing cell line (CATH.a).