Complex components of Shengmai formula interact with organic cation transporter 2 (OCT2) in MDCK cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Shengmai formula (SMF) is a well-known Chinese herbal compound preparation, which is utilized extensively for the treatment of myocardial ischemia, arrhythmia and other life-threatening conditions. Our previous researches have shown that some of the active ingredients in SMF can interact with organic anion transport polypeptide 1B1 (OATP1B1), breast cancer resistance protein (BCRP) and organic anion transporter 1 (OAT1), etc. Organic cation transporter 2 (OCT2) is a highly expressed uptake transporter in the kidney, and its interaction with the major active components in SMF remains unclear. AIM OF THE STUDY: We purposed to explore OCT2-mediated interactions and compatibility mechanisms of the main active compounds in SMF. MATERIALS AND METHODS: Fifteen active ingredients of SMF, including ginsenoside Rb1, Rd, Re, Rg1, Rf, Ro and Rc, methylophiopogonanone A and B, ophiopogonin D and D', schizandrin A and B, schizandrol A and B, were selected to investigate OCT2-mediated interactions in Madin-Darby cacine kidney (MDCK) cells stably expressing OCT2. RESULTS: Among the above 15 main active components, only ginsenosides Rd, Re and schizandrin B could significantly inhibit the uptake of 4-(4-(dimethylamino)styryl)-N-methyl pyridiniumiodide (ASP+), a classical substrate of OCT2. Ginsenoside Rb1 and methylophiopogonanone A can be transported by MDCK-OCT2 cells, and their uptake was significantly reduced when OCT2 inhibitor decynium-22 was added. Ginsenoside Rd could remarkably reduce the uptake of methylophiopogonanone A and ginsenoside Rb1 by OCT2, ginsenoside Re only decreased the uptake of ginsenoside Rb1, while schizandrin B had no effect on the uptake of both. CONCLUSIONS: OCT2 mediates the interaction of the major active components in SMF. Ginsenosides Rd, Re and schizandrin B are the potential inhibitors of OCT2, while ginsenosides Rb1 and methylophiopogonanone A are the potential substrates of OCT2. There is an OCT2-mediated compatibility mechanism among these active ingredients of SMF.

Dissolved metal assessment in surface seawater: A spatial-seasonal evaluation in the Zhejiang coastal waters, the East China Sea.

The spatial-seasonal distributions and variations, correlations with environmental variables and the pollution degrees of dissolved metals in the Zhejiang coastal seawater were investigated. The concentrations of six dissolved metals (i.e. Cu, Pb, Zn, Cd, As and Hg) were in the ranges of 0.10-6.40 (1.6 ± 0.8), 0.16-3.60 (1.2 ± 0.7), 2.50-24.0 (8.5 ± 4.8), 0.011-0.180 (0.07 ± 0.03), 0.85-4.20 (2.1 ± 0.8) and 0.001-0.110 (0.06 ± 0.02) µg/L, throughout the four seasons, respectively. Significant differences in all the dissolved metals were found among seasons, whereas no significant differences were found among stations. The average concentrations of metals were in the following order: Zn > As>Cu > Pb > Cd > Hg. Single metal contamination factor was in the following order: Pb > Hg > Zn > Cu > As>Cd. The pollution level of dissolved metals in the Zhejiang coastal waters (ZCW) was low. Most of the dissolved metals were correlated to temperature, indicating seasonal differences. The redundancy analysis (RDA) indicated that depth, temperature, nitrate and phosphate could best explain the variance pattern of dissolved metals in the ZCW.

Interaction of the main active components in Shengmai formula mediated by organic anion transporter 1 (OAT1).

ETHNOPHARMACOLOGICAL RELEVANCE: Shengmai formula (SMF) is a classical traditional Chinese medicine prescription, which is widely used in the treatment of cardiovascular and cerebrovascular diseases. Our previous studies have demonstrated that some components in SMF can interact with each other through breast cancer resistance protein, sodium taurocholate co-transporting polypeptide, organic anion transporting polypeptide 1B1 and 1B3. Organic anion transporter 1 (OAT1) is highly expressed in kidney, mediating the elimination of many endogenous and exogenous substances. However, the interaction between the main active components in SMF and OAT1 is not clear. AIM OF THE STUDY: This study aimed to investigate the interactions of the major bioactive components in SMF mediated by OAT1. MATERIALS AND METHODS: Four main fractions, namely, ginseng total saponins (GTS), ophiopogon total saponins (OTS), ophiopogon total flavonoids (OTF), fructus schisandrae total lignans (STL), and 12 active components, namely, ginsenoside Rg1, Re, Rd and Rb1, ophiopogonin D and D', methylophiopogonanone A and B, schizandrol A and B, schizandrin A and B, were selected to explore the interactions of SMF with OAT1 using cell and rat models. RESULTS: The above four main fractions in SMF all exhibited inhibitory effects on the uptake of 6-carboxyfluorescein (6-CF), a classic substrate of OAT1. Among the 12 main effective components, only ginsenoside Re, Rd, and methylophiopogonanone A showed inhibition of 6-CF uptake. Additionally, we found that schizandrin B was transported by HEK293-OAT1 cells, and schizandrin B uptake was markedly inhibited by GTS, OTS, OTF, ginsenoside Re, Rd, and methylophiopogonanone A. In rats, ginsenoside Re, Rd, and methylophiopogonanone A jointly increased the AUC(0-t), AUC(0-∞), and Cmax of schizandrin B, but they decreased its clearance in plasma and excretion in urine. CONCLUSIONS: Ginsenoside Re, Rd, and methylophiopogonanone A were the potential inhibitors of OAT1, and may interact with some drugs serving as OAT1 substrates clinically. Schizandrin B was a potential OAT1 substrate, and its OAT1-mediated transport was inhibited by ginsenoside Re, Rd, and methylophiopogonanone A. OAT1-mediated interactions of the main active components in SMF can be regarded as one of the important compatibility mechanisms of traditional Chinese medicine preparations.

Outcome of in vitro fertilization in women with subclinical hypothyroidism.

BACKGROUND: Previous studies examining associations between subclinical hypothyroidism (SCH) with in vitro fertilization (IVF) outcome indicate some benefits of levothyroxine (LT4) treatment. But IVF outcomes in treated SCH women whose serum Thyroid Stimulating Hormone (TSH) concentration did and did not exceed 2.5 mIU/L before the IVF cycle has not been studied thoroughly. METHODS: In this study, we performed a prospective cohort study with 270 treated subclinical hypothyroidism patients undergoing their first IVF retrieval cycle at a single cite. RESULTS: SCH in women receiving LT4 replacement with a basal TSH level between 0.2-2.5mIU/L displayed a similar rate of clinical pregnancy (47.4% vs 38.7%, P = .436), miscarriage (7.4% vs 16.7%, P = .379) and live birth (43.9% vs 32.3%, P = .288) compared to women with a basal TSH level between 2.5-4.2 mIU/L. CONCLUSION: Strictly controlled TSH (less than 2.5 mIU/L) before IVF may have no effect on the pregnancy rate in LT4 treated SCH women.

[Comparison of ultrasound plus radiography versus computed tomography in the diagnosis of ectopic intrauterine devices].

OBJECTIVE: To compare the effectiveness of ultrasound plus radiography versus computed tomography (CT) in the diagnosis of ectopic intrauterine device (IUD) and analyze the ratio of cost and effectiveness (C/E) so as to provide scientific rationales for the selection of appropriate diagnostic methods. METHODS: A total of 70 cases were recruited from two major Chinese hospitals in 2009. They were examined with ultrasound plus radiography and CT respectively. The gold diagnostic criterion was postoperative diagnosis to compare the sensitivity, specificity, diagnostic index (DI), accuracy and C/E for different diagnostic methods. The SPSS 13.0 statistical analysis software was employed for data analysis. RESULTS: The data of 65 subjects were collected and analyzed. For ultrasound plus radiography, the sensitivity, specificity, DI, accuracy and C/E were 82.1%, 88.9%, 171.0%, 83.1% and 137.3 respectively. As for CT, the above indices were 96.4%, 55.6%, 152.0%, 90.8% and 170.7 respectively. CONCLUSION: Considering the higher levels of specificity and DI and a lower C/E, ultrasound plus radiography is superior to CT so that the former modality shall become a first-choice in the diagnosis of ectopic IUD, especially at the grass-root family planning service stations.