Protective properties of a fusion pneumococcal surface protein A (PspA) vaccine against pneumococcal challenge by five different PspA clades in mice

An increase in the appearance of nonvaccine serotypes in both children and adults with invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccine represents a limitation of this vaccine. In this study, we generated three recombinant pneumococcal surface protein A (PspA) proteins comprising PspA families 1 and 2, and we examined the reactivity of antisera raised in mice immunized with a PspA fusion protein in combination with CpG oligonucleotides plus aluminum hydroxide gel. The protective effects of immunization with PspA fusion proteins against pneumococcal challenge by strains with five different PspA clades were also examined in mice. Flow cytometry demonstrated that PspA3+2-induced antiserum showed the greatest binding of PspA-specific IgG to all five challenge strains with different clades. PspA2+4- or PspA2+5-induced antiserum showed the lowest binding of PspA-specific IgG to clade 3. Immunization with PspA3+2 afforded significant protection against pneumococcal challenge by five strains with different clades in mice, but immunization with PspA2+4 or PspA2+5 failed to protect mice from pneumococcal challenge by strains with clades 1 and 3. The binding of PspA-specific IgG in antisera raised by three PspA fusion proteins was examined in 68 clinical isolates from adult patients with IPD. Immunization of mice with PspA3+2-induced antiserum with a high binding capacity for clinical isolates expressing clades 1–4, but not clade 5. Our results suggest that the PspA3+2 vaccine has an advantage over the PspA2+4 or PspA2+5 vaccine in terms of a broad range of cross-reactivity with clinical isolates and cross-protection against pneumococcal challenge in mice.     

Ref-1 protects against FeCl3-induced thrombosis and tissue factor expression via the GSK3β–NF-κB pathway

Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl₃ solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl₃ aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction via the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref-1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM-1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.     

抗凝与促凝药物交替应用治疗血栓合并出血患者1例分析

摘 要1例72岁女性患者,因“ 慢性咳嗽、咳痰、呼吸困难10年,加重伴间断发热1个月”入院,诊断为慢性支气管炎急性发作,慢性肺源性心脏病,心功能Ⅳ级,双下肢静脉血栓,血小板减少。患者在治疗中需要权衡抗凝药物与促凝药物的应用,在制定方案时利用房颤出血评分系统结合患者临床实际进行出血风险的评估,同时考虑药物之间的相互作用可能对患者产生的危害和用缜密的临床思维来评估患者的预后,减少了患者用药风险。     

Effects of morin on the pharmacokinetics of nicardipine after oral and intravenous administration of nicardipine in rats

This study investigated the effects of orally administered morin, an inhibitor of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), on the pharmacokinetics of orally and intravenously administered nicardipine in rats. Nicardipine is reportedly a substrate for CYP3A4 and P-gp. Nicardipine was administered orally (12 mgkg(-1)) with or without orally administered morin (1.5, 7.5 and 15 mgkg(-1)), and intravenously (4 mgkg(-1)) with or without orally administered morin (7.5 and 15 mgkg(-1)). In the presence of morin, the pharmacokinetic parameters of nicardipine were significantly altered in the oral group but not in the intravenous group, suggesting that CYP3A-mediated metabolism of nicardipine in the liver is not significantly inhibited by morin. The presence of 7.5 and 15 mgkg(-1) of morin significantly increased (P < 0.01, 67.8-112%) the area under the plasma concentration-time curve and the peak plasma concentration (P < 0.01, 53.5-93.1%) of orally administered nicardipine. The presence of 7.5 and 15 mgkg(-1) of morin significantly decreased (P < 0.01, 40.4-52.8%) the total body clearance of orally administered nicardipine compared with the control group. The enhanced oral bioavailability of nicardipine suggests that intestinal-mediated CYP3A4 metabolism and P-gp-mediated efflux of nicardipine are inhibited by morin. Based on these results, concomitant use of morin or morin-containing dietary supplements with nicardipine may require close monitoring for potential drug interactions.     

Preparation and in vivo evaluation of piroxicam-loaded gelatin microcapsule by spray drying technique

To develop a piroxicam-loaded gelatin microcapsule with enhanced bioavailability, a gelatin microcapsule encapsulated ethanol and piroxicam has been formulated by using gelatin as a water-soluble polymer shell. The aqueous solubility and bioavailability of piroxicam in piroxicam-loaded microcapsule in rats were then evaluated compared to piroxicam powder. The piroxicam-loaded gelatin microcapsule spherical in shape with smooth surface showed the geometric mean diameter of about 19 microm. It had the piroxicam solubility of about 1.87 mg/ml and the amount of ethanol of about 4.37 microg/mg. Furthermore, it gave significantly higher total plasma concentrations, Cmax and area under the blood concentration-time curve (AUC) of piroxicam in rats than did piroxicam powder, indicating that the drug from gelatin microcapsule could be more orally absorbed in rats. In particular, the AUC of piroxicam in gelatin microcapsule was significantly about 2 fold increased compared to piroxicam powder. This enhanced oral relative bioavailability of piroxicam in gelatin microcapsule was contributed by the marked increase in the absorption rate of piroxicam due to the improved solubility of piroxicam. Thus, the piroxicam-loaded gelatin microcapsule developed using spray-drying technique with gelatin, sodium lauryl sulfate and ethanol would be useful to deliver piroxicam in a pattern that allows fast absorption in the initial phase, leading to better absorption.     

防风化学成分的研究

从防风甲醇提取物中分离得到11个结晶,分别鉴定为β-谷甾醇,香柑内酯,亥茅酚,胡萝卜甙,sec-O-glncosylhamaudol,5-O-甲基维斯阿米醇,升麻素,蔗糖,4-O-β-glucopyranosyl-5-O-methylvisamminol,prim-O-glucosylcimifugin,甘露醇。     

开郁清胃颗粒对2型糖尿病胰岛素敏感性的影响

目的：通过临床观察初步探讨开郁清胃颗粒对2型糖尿病患者胰岛素敏感性的影响。方法：以二甲双胍为对照，观察60例2型糖尿病患者治疗前后体重及腰臀围、症状积分、血糖、胰岛素、胰岛素敏感指数、血脂、焦虑及抑郁积分等指标的变化。结果：开郁清胃颗粒对2型糖尿病患者的血糖、血脂紊乱有明显的改善作用，并能减轻体重，提高胰岛素敏感性，改善焦虑及抑郁状态。结论：开郁清胃颗粒增加2型糖尿病患者的胰岛素敏感性可能与改善血脂紊乱，改善焦虑、抑郁状态及减轻体重等有关。     

鹿茸口服液对抗氧化酶的影响

目的:研究鹿茸口服液对青年及老年小鼠的抗氧化作用.方法:灌服鹿茸口服液后,测定小鼠SOD、CAT和GSHpx活性及MDA含量.结果:鹿茸口服液对老年小鼠SOD活性增强和MDA含量降低作用均明显强于对青年小鼠,并能增强老年小鼠肝CAT和GSHpx活性.结论:鹿茸口服液对老年小鼠具有抗氧化作用.     

Early dengue outbreak detection modeling based on dengue incidences in Singapore during 2012 to 2017

Dengue has been as an endemic with year-round presence in Singapore. In the recent years 2013, 2014, and 2016, there were several severe dengue outbreaks, posing serious threat to the public health. To proactively control and mitigate the disease spread, early warnings of dengue outbreaks, at which there are rapid and large-scale spread of dengue incidences, are extremely helpful. In this study, a two-step framework is proposed to predict dengue outbreaks and it is evaluated based on the dengue incidences in Singapore during 2012 to 2017. First, a generalized additive model (GAM) is trained based on the weekly dengue incidence data during 2006 to 2011. The proposed GAM is a one-week-ahead forecasting model, and it inherently accounts for the possible correlation among the historical incidence data, making the residuals approximately normally distributed. Then, an exponentially weighted moving average (EWMA) control chart is proposed to sequentially monitor the weekly residuals during 2012 to 2017. Our investigation shows that the proposed two-step framework is able to give persistent signals at the early stage of the outbreaks in 2013, 2014, and 2016, which provides early alerts of outbreaks and wins time for the early interventions and the preparation of necessary public health resources. In addition, extensive simulations show that the proposed method is comparable to other potential outbreak detection methods and it is robust to the underlying data-generating mechanisms.