Yong-jie Wang, Yi-bo Wang, Dun-wei Du and Yan-ping Bai
Qiong Yi, Xin Li, Yuan-Fang Li, Hang Yang, Xiao-Yi Zhang, Zhe Ma and Lu Wang
Introduction: The effects of Jin-Ying-Tang (JYT) on Toll-like Receptor 4 (TLR4) signalling transduction of lipopolysaccharide (LPS)-stimulated mouse mammary epithelial cells (MECs) in vitro were examined. Material and Methods: The cytotoxicity of JYT (0.06-62.50 mg/mL) on mouse MECs was determined by MTT assay. The MECs were co-cultured with LPS in the presence or absence of JYT (39.10 μg/mL, 391 μg/mL, 3910 μg/mL). The concentrations of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in the culture supernatants were detected by ELISA. The mRNA expression of TLR4 and downstream TLR4 signalling molecules such as myeloid differentiation factor 88 (MyD88), tumour necrosis factor receptor associated factor 6 (TRAF-6), inhibitor κB (IκB), and nuclear factor κB inducing kinase (NIK) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The results showed that the IC50 of JYT on MECs was 12.25 mg/mL and JYT could significantly decrease the concentrations of IL-6 and TNF-α in LPS-stimulated MECs (P < 0.05). The mRNA expression of TLR4, MyD88, TRAF-6, IκB, and NIK was also significantly decreased when the LPS-stimulated MECs were cocultured at appropriate concentrations of JYT (P < 0.05, P < 0.01). Conclusion: These observations indicate a potential mechanism through which JYT attenuates the systemic inflammatory response to LPS-stimulated mouse mammary epithelial cells by inhibiting the activation of TLR4/MyD88/ TRAF-6/NIK pathway at the mRNA level.
Yun-de Shen, Jing-yi Zhang, Su-jie Zhou, Lei Wang and Dong-ji Xuan
Yi Xu, Wei-wei Fu, Shi Chen, Yue-fang Dong, Ke-ke Gu and Li-ping Wang
Fugen Gu, Jia Ning, Huimin Fan, Chunzhi Wu and Yi Wang
Simvastatin is poorly bioavailable because it is practically insoluble in water and shows dissolution rate-limited absorption. Solubilizing effects of several β-cyclodextrin (βCD) derivatives such as HPβCD, SBEβCD and DMβCD on simvastatin in aqueous solution were investigated using the phase solubility technique. The solubility diagram of simvastatin with each βCD derivative could be classified as AL-type, indicating soluble complex formation of 1:1 stoichiometry. Among the above βCD derivatives DMβCD was found to be the ideal complexing agent for improving drug solubility. The simvastatin complex with DMβCD was prepared using the co-evaporation method and was then characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and in vitro dissolution. Dissolution and pharmacokinetic studies indicated that the simvastatin/DMβCD complex exhibited an increased dissolution rate, rapid absorption, and improved bioavailability in rats compared to free drug. Maximum plasma concentration (c max) and the time to reach it (t max) were 21.86 μg mL−1 and 1.4 h for the drug complex, 8.25 μg mL−1 and 3.0 h for free drug, respectively. Main pharmacokinetic parameters such as t max, c max were significantly different (p < 0.01) between the simvastatin complex and free drug. Bioavailability of the simvastatin complex relative to free drug was up to 167.0 %.
Fugen Gu, Weina Ma, Gendalai Meng, Chunzhi Wu and Yi Wang
The aim of this study was to prepare a nasal gel of risperidone and to investigate the pharmacokinetics and relative bioavailability of the drug in rats. Compared with oral dosing, the risperidone nasal gel exhibited very fast absorption and high bioavailability. Maximal plasma concentration (cmax) and the time to reach cmax (tmax) were 15.2 μg mL-1 and 5 min for the nasal gel, 3.6 μg mL-1 and 30 min for the oral drug suspension, respectively. Pharmacokinetic parameters such as tmax′, cmax and AUC of oral and nasal routes were significantly different (p < 0.01). Relative bioavailability of the drug nasal preparation to the oral suspension was up to 1600.0 %. Further, the in vitro effect of the risperidone nasal gel on nasal mucociliary movement was also investigated using a toad palate model. The risperidone nasal formulation showed mild ciliotoxicity, but the adverse effect was temporary and reversible.
Yi Wang, Yu-yuan Li and Wen Guo
Objectives To investigate that given a fixed amount of financial resources, what is the optimal combination of vaccine and antiviral stockpiles in terms of minimizing the attack rate.
Methods Mathematic modeling was used to simulate the dynamics that with fixed influenza pandemic budget. Different budget conditions were observed if the combination changed. Framework between vaccines and antivirals was introduced by taking into account the uncertainty in vaccine and antiviral efficacy.
Results Given a fixed budget, different budget allocations between vaccines and antivirals stockpile gave different attack rates. When the price of vaccine was lower than or similar with the antivirals, the attack rate increased with increasing investment in antiviral. But if the price of the vaccine was higher than the antivirals, the attack rate may not decrease with increasing investment in vaccine. Fixed the vaccine effectiveness, higher effectiveness of antiviral got a lower attack rate.When both antiviral and vaccine were with 50% probability of effectiveness, the attack rate changed by antiviral stockpile with a same pattern as they were with 100% efficacy probability, even it has a higher attack rate.
Conclusions Assume the antivirals have 100% probability to be effective, budget was limited to a fix number, then in any event, population should stockpile a small amount of antivirals such that if the post-vaccination reproductive number turns out to be near 1, the additional intervention may further reduce the reproductive number to <1 and prevent the epidemic. Under the fixed budget, the price of the vaccines and antivirals will strongly affect the strategy of the stockpile allocation. When the price of vaccine is comparative lower, more investment of vaccine is better for the pandemic control, but if the vaccine price is too high then more investment in antiviral may be better. We found that attack rates and the optimal budget allocation depend on the probability to be effective of vaccine and antivirals.
Shifang Ding, Yi Peng, Zhinan Chen, Juquan Jiang, Zhigang Gong, Zhigang Li, Qing Lu and Renxue Wang
Prognostic Value of High-Sensitivity C-Reactive Protein and Lipoprotein (a) in Acute Myocardial Infarction Patients Receiving Emergency Percutaneous Coronary Intervention
In order to study the prognostic value of high-sensitivity C-reactive protein (hsCRP) and lipoprotein (a) [Lp(a)] in patients receiving emergency percutaneous coronary intervention (PCI) following acute myocardial infarction (AMI), we retrospectively reviewed 118 patients who received emergency PCI following AMI from January 2007 to April 2010. The plasma levels of hsCRP and Lp(a) were determined. The incidence of cardiovascular events was compared between patients with an elevated hsCRP level and those with a normal hsCRP level and between patients with an elevated Lp(a) level and those with a normal Lp(a) level. Results showed that the incidence of cardiovascular events was 52.9% in the hsCRP-elevated group and 18.2% in the hsCRP-normal group displaying a significant difference (P=0.011). However, the incidence of cardiovascular events was 35.3% in the Lp(a)-elevated group and 46.4% in the Lp(a)-normal group and statistical analysis revealed no significant difference (P=0.733). HsCRP, but not Lp(a), can serve as a prognostic factor for patients receiving emergency PCI following AMI.
Kai Wang, Yu Qi, Shushuai Yi, Zhihua Pei, Na Pan and Guixue Hu
Introduction: The aim of the experiment was to establish the enterotoxigenic Escherichia coli K88 (ETEC K88)-induced BALB/c mouse duodenum inflammation model. Material and Methods: Mice were administered different concentrations of E. coli K88 (1.0 × 107-109 CFU/mL) for 3 d by means of an esophageal catheter. Results: The results showed that the treated group expressed several significant clinical symptoms, such as reduced dietary demands and weight loss, an increased presence of IL-1α, TNF-α, and MPO in the peripheral blood, and some pathological changes in the duodenum. On the 6th-8th days, the body weight of the mice was the lowest. On the 8th day, there were significant differences in IL-1α, TNF-α, and MPO levels compared to the control group (P < 0.05), the gap between the duodenum mucous layer and the muscular layer had widened, the number of goblet cells was increased, and the inflammatory infiltrate and inflammation changes in the lamina propria and the mucous layer were the most obvious. Conclusion: The duodenum inflammation was the most severe on day 8; thus, the model was successfully established. In addition, varying concentrations of ETEC K88 did not significantly influence the duodenum inflammation (P > 0.05).
Tong-Sheng Wang, Xiu-Li Su, Yi-Min Mao and Yu-Xia Sun
Background: Despite important advances in the diagnosis and treatment of acute pulmonary embolism (APE), diagnosis of pulmonary embolism (PE) is difficult in patients with chronic obstructive pulmonary disease (COPD) and exacerbation.
Objective: We evaluated PE in patients with chronic obstructive pulmonary disease and exacerbations of unknown origin.
Methods: Two-hundred and eight patients with COPD and severe exacerbations were studied. All patients had CT pulmonary angiography (CTPA) and lower limb ultrasonography. Arterial blood gas measurements, D-dimers and endothelin-1 (ET-1) levels were recorded.
Results: The frequency of PE was 33%. The following were more common in the PE group (χ2 = 4.32-6.79, mean p < 0.05): immobilization ≥ 7 days; a ≥ 1 cm difference in edema of the lower limbs; deep venous thrombosis; syncope; S1Q3T3 syndrome; and a decrease in PaCO2 ≥ 5 mm Hg. Plasma D-dimers and ET-1 levels were significantly higher in the PE group. Risk factors identified from logistic regression analysis were immobilization ≥ 7 days, ≥ 1 cm difference in lower limb edema, and deep venous thrombosis.
Conclusions: Overall, 33% of 208 patients had a PE, and the risk was greater in those who had been immobilized, those who had a ≥ 1 cm difference in edema of the lower limbs, and those who had a deep venous thrombosis.