OBJECTIVE: To compare the midtrimester triple marker levels for down syndrome screening between natural and IVF twin pregnancies and to evaluate the difference triple marker in IVF twin pregnancies according to the fertilization method and number of transferred embryos. METHODS: The study population consisted of conventional IVF twin (n=106), ICSI twin (n=142), and natural (n=436) twin pregnancies as controls between 2001 and 2004. All pregnancies in this study were known to have normal outcome. Maternal serum samples were collected between 14-18 gestational weeks. Levels of AFP, total hCG, and uE3 were measured and were expressed as multiples of the median (MoM) based on reference medians established at Cheil Hospital. RESULTS: The mean maternal age (31.6+/-2.8 vs. 31.6+/-3.0 vs. 32.1+/-2.1: conventional IVF group vs. ICSI group vs. control, respectively) and gestational weeks (16.0+/-0.5 vs. 16.0+/-0.7 vs. 16.1+/-0.2) for triple test were similar. There was no difference in levels of all serum markers between conventional IVF and ICSI group. The median AFP MoM for conventional IVF and ICSI group were significantly higher than that of the control group (2.40 vs. 2.22 vs. 1.98; p<0.05). However, the median uE3 MoM for conventional IVF or ICSI group were not different from that of the control group (1.78 vs. 1.72 vs. 1.83; p>0.05). Also, the median hCG MoM was not different from that of the control group (2.04 vs. 2.06 vs. 2.02; p>0.05). There was no correlation in triple marker levels according to the number of transferred embryos in conventional IVF and ICSI groups. CONCLUSION: Midtrimester triple marker levels of IVF twin pregnancy for down syndrome screening are similar with those of natural twin pregnancy regardless of fertilization method and number of transferred embryos.
Biomarkers ; Down Syndrome ; Embryonic Structures ; Female ; Fertilization ; Humans ; Mass Screening ; Maternal Age ; Pregnancy ; Pregnancy Trimester, Second* ; Pregnancy, Twin* ; Sperm Injections, Intracytoplasmic

Precise mechanism which the fetus can escape from mother's immune rejection is not well understood yet during last 50 years. The clarification of immune mechanism at the feto-maternal interface is very important, because this can be a common pathogenesis of various pathologic conditions including spontaneous abortion and habitual abortion. The pivot of this mechanism is cross-talk between the expression of HLA-C, E, G on the extravillous cytotrophoblasts and their receptors on decidual NK (natural killer) cell. The mechanism through which HLA-C, E, G regulation on the extravillous trophoblast is poorly understood. The IFN-gamma is known to be harmful to the successful maintenance of early pregnancy. OBJECTIVE: To clarify whether the IFN-gamma could be involved in the regulation of the HTR-8/SVneo human first trimester cell line. METHODS: We investigated the effects of IFN-gamma only or with other cytokines on the HLA-C, E, G transcripts in human first trimester trophoblast cell-line by using Reverse Transcription Polymerase Chain Reaction (RT-PCR). RESULTS: The trophoblast cells expressed HLA-C, E constitutively. When cultured in the presence of IFN-gamma only or with other cytokines, HLA-C, E transcripts were not significantly affected. CONCLUSION: These results suggest that harmful IFN-gamma to maintain early pregnancy may affect through another mechanism besides regulation of HLA-C, E on the extravillous cytotrophoblasts at the feto-maternal interface.
Abortion, Habitual ; Abortion, Spontaneous ; Cell Line* ; Cytokines ; Female ; Fetus ; HLA Antigens* ; HLA-C Antigens ; Humans* ; Interferon-gamma* ; Polymerase Chain Reaction ; Pregnancy ; Pregnancy Trimester, First* ; Reverse Transcription ; Trophoblasts* ; United Nations

Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their inter-assay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.
Citric Acid* ; Colitis ; Cytochrome P-450 CYP1A2 ; Cytochrome P-450 Enzyme System* ; Cytochromes* ; Drug Discovery ; Enzyme Induction* ; Fireflies ; Hepatocytes ; Humans* ; Isoenzymes ; Liver ; Luciferases ; Luminescence ; Luminescent Measurements* ; Mass Screening ; Mesalamine* ; Metabolism ; RNA, Messenger

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 muM in patch clamp assay and increased the heart rate and blood pressure (76 Deltabpm in heart rate and 51 DeltammHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 muM and 30 muM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.
Action Potentials ; Animals ; Blood Pressure ; Cardiovascular System ; Counterfeit Drugs ; Dogs ; Heart Rate ; HEK293 Cells ; Inhibitory Concentration 50 ; Pharmaceutical Preparations ; Pharmacology* ; Purkinje Fibers ; Rabbits ; Telemetry