Effect of Wuziyanzong pill on metabolism of dapoxetine in vivo and in vitro.

In vitro incubation of rat liver microsomes with 30 µL of 100 µmol·L-1 dapoxetine and 30 µL of 10, 100, 250, 500, 1000, 2500, or 5000 µg·mL-1 Wuziyanzong pill was performed at 37 °C for 60 min. Dapoxetine concentration was analyzed by high performance liquid chromatography (HPLC). The half maximal inhibitory concentration (IC50) of Wuziyanzong pill on metabolism of dapoxetine was 296.10 µg mL-1in vitro. Twelve SD rats were randomly divided into 2 groups: Control group and Wuziyanzong pill group. The two groups were administrated with 10 mL·kg-1 saline (Control group) or 10 mL·kg-1 Wuziyanzong pill solution (Experimental group, solution contained 200 mg mL-1 Wuziyanzong pill) for 15 consecutive days. Following administration of saline or Wuziyanzong pill on the 15th day, 20 mg kg-1 dapoxetine was administered to all rats. Blood was collected from the tail vein (0.3 mL) at multiple time points, and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was used to determine the concentration of dapoxetine and its main metabolites, dapoxetine-N-oxide and desmethyldapoxetine in rats. Pharmacokinetic analysis of dapoxetine showed that area under the concentration-time curve (AUC) and mean maximum plasma concentration (Cmax) of the Wuziyanzong pill group were decreased, while plasma clearance (CLz) was increased compared with control group (P < 0.01). The HPLC method for determination of dapoxetine in vitro was accurate and specific. The UHPLC-MS/MS method established for determination of dapoxetine and its major metabolites in rat plasma was rapid and specific, which met the requirements of pharmacokinetic guidelines. Wuziyanzong pill had a weak inhibitory effect on metabolism of dapoxetine in vitro, but had a very strong induction effect in vivo, suggesting the dosage of dapoxetine should be increased when administered in combination with Wuziyanzong pill.

Quantitative analysis of tivantinib in rat plasma using ultra performance liquid chromatography with tandem mass spectrometry.

In this work, a simple, sensitive and fast ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitative determination of tivantinib in rat plasma. Plasma samples were processed with a protein precipitation. The separation was achieved by an Acquity UPLC BEH C18 (2.1mm×50mm, 1.7µm) column with a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The validated method had an excellent linearity in the range of 1.0-100ng/mL (r(2)>0.9967) with a lower limit of quantification (1.0ng/mL). The extraction recovery was in the range of 79.4-84.2% for tivantinib and 80.3% for carbamazepine (internal standard, IS). The intra- and inter-day precision was below 8.9% and accuracy was from -7.2% to 9.5%. No notable matrix effect and astaticism was observed for tivantinib. The method has been successfully applied to a pharmacokinetic study of tivantinib in rats for the first time, which provides the basis for the further development and application of tivantinib.

Curcumin inhibited hypoxia induced epithelial-mesenchymal transition in hepatic carcinoma cell line HepG2 in vitro / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore effects and possible mechanisms of curcumin on hypoxia induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma cell line HepG2.</p><p><b>METHODS</b>HepG2 cells were divided to 3 groups, i.e., the normal control group, the CoCl2 group, and the CoCl2 plus 10 micromol/L curcumin group. The proliferation of HepG2 was determined using MTT assay. The migration of HepG2 was detected by wound healing assay.The mRNA expression of hypoxia-inducible factor-1 (HIF-1alpha) was evaluated with real-time RT-PCR. The protein expressions of HIF-1alpha, epithelial-cadherin (E-cadherin), and vimentin were determined using Western blot.</p><p><b>RESULTS</b>Compared with the normal control group, the proliferation and migration of HepG2 cells under CoCl2-induced hypoxia significantly increased, the expression of HIF-1alpha was up-regulated, and the expression of E-cadherin protein was obviously down-regulated, and the expression of vimentin significantly increased (all P < 0.05). Intervention by curcumin significantly inhibited the proliferation and migration of hypoxic HepG2 cells, and expressions of HIF-1alpha and vimentin decreased, and the expression of E-cadherin was up-regulated, showing statistical difference when compared with those of the CoCl2 group (P < 0.05). There was no statistical difference in HIF-1alpha mRNA expression among the 3 groups (P > 0.05).</p><p><b>CONCLUSION</b>Curcumin could reverse the proliferation and migration of HepG2 cells under CoCl2-induced hypoxia condition, which might be associated with inhibiting up-regulated expressions of HIF-1alpha protein and EMT.</p>

Surveillance for schistosomiasis japonica in China from 2000 to 2003.

According to the protocol of the national surveillance project, longitudinal observation of the endemic situation of schistosomiasis japonica in China has been carried out at 20 sentinel surveillance sites, commencing in 2000. After four years of surveillance, the infection rate of Schistosoma japonicum gradually decreased in seven sentinel sites. In 10 sites, infection rates remained relatively stable over time, while there was a marked increase in one site. No clear trend became apparent in the remaining two sites. Significant reductions of densities of living intermediate host snails and infected snails were noted in only two sites. In turn, the endemic situation was not well controlled in most of the other sentinel sites. The infection cattle rate fluctuated yearly in the majority of the sites and maintained a high level. During the four years of surveillance, acute cases of schistosomiasis japonica among humans were found in each of the yearly cross-sectional surveys, and the number of patients with advanced schistosomiasis did not change significantly. The surveillance results obtained thus far indicate that current control strategies continue to reduce morbidity due to schistosomiasis. However, concerted control efforts must continue for a long time and the surveillance of intermediate host snail and animal reservoirs (e.g. cattle) should be strengthened.

Relationship between the transmission of schistosomiasis japonica and the construction of the Three Gorge Reservoir.

OBJECTIVE: To study the relationship between the changes of environment and the transmission of Schistosomiasis japonica after the construction of the Three Gorge Reservoir. METHODS: On the basis of the predictive data on changes of water level and sediment in the middle and lower reaches of the Yangtze River after the dam construction provided by the Yangtze River Committee on Water Conservancy, corresponding data were collected and analyzed. In order to understand the effects of changes of water level and sediment on Oncomelania hupensis, the intermediate host of Schistosoma japonicum, field surveys and ecologically intimated experiments were done. The prevalence status and factors related to transmission were investigated by epidemiology, medical geography and public health. RESULTS: Positive impact on control of schistosomiasis is that floods in the Yangtze River will occur less and will decrease the dispersal of snails and the chances of infection for humans and animals as well. Snail habitats' beach will be reduced in the flushed area along the Yangtze River. Exploitation of beach and elimination of snails will benefit from the beach's uplift in flushed area. The floods ahead of time in autumn will interfere with the development of snails. Negative impact is that the flushed beaches and migratory settlements at certain altitude may become snail habitats. So the reservoir area will be a potential transmission area of schistosomiasis due to dispersal of infectious resources and Oncomelania snails. The uprising of the water body level may cause the expending of the snail habitats in some places of Jianghan plain during the transition of spring to summer. The destruction of the embankments of the Dongting Lake will be put off by its delayed flush, which causes the beach in a situation of growing reed-grass or grass for a long time that benefits the reproduction of the snails. The chances for schistosome infection to humans and animals will be on the increase, because the water regression occurs ahead of time in the Dongting Lake beach in autumn. The distribution of snails will not be affected by the changes of water level in the lower reaches of the Yangtze River after the dam is built, but the flushed section in Anhui in the recent 80 years are suitable for the snails' development. The environmental changes due to dam construction will not obviously affect the development of snails and the transmission of schistosomiasis in the Poyang Lake area. CONCLUSION: The construction of the huge dam and the formation of the Three Gorge Reservoir on the Yangtze River may have both positive and negative impact on schistosomiasis transmission and control. Great effort must be made to decrease the negative impact to avoid or, at least, to decrease S. japonicum transmission.