Biological effect of food additive titanium dioxide nanoparticles on intestine: an in vitro study

Titanium dioxide nanoparticles (TiO₂ NPs) are widely found in food‐related consumer products. Understanding the effect of TiO₂ NPs on the intestinal barrier and absorption is essential and vital for the safety assessment of orally administrated TiO₂ NPs. In this study, the cytotoxicity and translocation of two native TiO₂ NPs, and these two TiO₂ NPs pretreated with the digestion simulation fluid or bovine serum albumin were investigated in undifferentiated Caco‐2 cells, differentiated Caco‐2 cells and Caco‐2 monolayer. TiO₂ NPs with a concentration less than 200 µg ml^–1 did not induce any toxicity in differentiated cells and Caco‐2 monolayer after 24 h exposure. However, TiO₂ NPs pretreated with digestion simulation fluids at 200 µg ml^–1 inhibited the growth of undifferentiated Caco‐2 cells. Undifferentiated Caco‐2 cells swallowed native TiO₂ NPs easily, but not pretreated NPs, implying the protein coating on NPs impeded the cellular uptake. Compared with undifferentiated cells, differentiated ones possessed much lower uptake ability of these TiO₂ NPs. Similarly, the traverse of TiO₂ NPs through the Caco‐2 monolayer was also negligible. Therefore, we infer the possibility of TiO₂ NPs traversing through the intestine of animal or human after oral intake is quite low. This study provides valuable information for the risk assessment of TiO₂ NPs in food. Copyright © 2015 John Wiley & Sons, Ltd.     

Correlation between osteocalcin‐positive endothelial progenitor cells and spotty calcification in patients with coronary artery disease

Immature endothelial progenitor cells (EPC) carrying osteocalcin (OCN) might mediate vascUlar calcification in coronary artery disease (CAD). Spotty calcification within atherosclerotic plaque is associated with cardiovascular events. The aim of the present study was to assess the correlation between immature EPC levels and spotty calcification in CAD patients. In the 224 CAD patients studied, 76 had acute myocardial infarction (AMI), 102 had unstable angina pectoris (UAP), and 46 had stable angina pectoris (SAP). The levels of OCN‐positive (OCN+) EPC were analysed by flow cytometry. The status of spotty calcification was determined by cardiac computed tomography angiography. OCN+ EPC and calcium deposits were significantly increased in acute coronary artery syndrome (ACS) when compared with those in SAP patients. Positive correlation was also revealed between the number of OCN+ EPC and the frequency of spotty calcification and levels of serum high‐sensitivity C‐reactive protein (hs‐CRP) and serum alkaline phosphatase in AMI and UAP patients. In summary, the number of OCN+ EPC is positively related to the frequency of spotty calcification in ACS patients. Serum hs‐CRP and serum alkaline levels are thought to contribute to the elevation of OCN+ EPC.     

Sequence Type 4821 Clonal Complex Serogroup B Neisseria meningitidis in China, 1978–2013

Serogroup B Neisseria meningitidis strains belonging to sequence type 4821 clonal complex (CC4821), a hyperinvasive lineage first identified for serogroup C in 2003, have been increasingly isolated in China. We characterized the outer membrane protein genes of 48 serogroup B and 214 serogroup C strains belonging to CC4821 and analyzed the genomic sequences of 22 strains. Four serogroup B strains had porin A (i.e., PorA), PorB, and ferric enterobactin transport (i.e., FetA) genotypes identical to those for serogroup C. Phylogenetic analysis of the genomic sequences showed that the 22 CC4821 strains from patients and healthy carriers were unevenly clustered into 2 closely related groups; each group contained serogroup B and C strains. Serogroup B strains appeared variable at the capsule locus, and several recombination events had occurred at uncertain breakpoints. These findings suggest that CC4821 serogroup C N. meningitidis is the probable origin of highly pathogenic CC4821 serogroup B strains.     

46例社区获得性肺炎门诊初始治疗失败原因的临床分析

目的分析社区获得性肺炎门诊初始治疗失败的原因。方法对昆明理工大学医院2012年5月-2014年6月诊断为社区获得性肺炎初始治疗失败的46例病例进行回顾性分析。结果初始治疗失败病例中,抗菌使用药物分布情况:头孢类25例,青霉素类13例,氟喹诺酮类8例;年龄分布情况:60岁以下者11人,占24%;60岁以上者35例,占76%。结论选择社区获得性肺炎抗感染药物时要充分考虑混合感染,要将社区获得性肺炎指南与本地区耐药情况结合,药理学知识与患者自身情况结合,合理使用抗菌药物,提高临床有效率。     

Antigen-conjugated N-trimethylaminoethylmethacrylate Chitosan Nanoparticles Induce Strong Immune Responses After Nasal Administration

Pharmaceutical Research - Antigens were conjugated on the surface of N-trimethylaminoethylmethacrylate chitosan (TMC) nanoparticles to induce systemic and mucosal immune responses after nasal...     

R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

(±)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of (±)-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions. We found that R-MOD is more potent and effective than S-MOD in attenuating nicotine self-administration in Long–Evans rats. As Long–Evans rats did not show a robust reinstatement response to nicotine, we used alcohol-preferring rats (P-rats) that display much higher reinstatement responses to nicotine than Long–Evans rats. We found that R-MOD significantly inhibited intravenous nicotine self-administration, nicotine-induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior in P-rats. R-MOD alone neither sustained self-administration in P-rats previously self-administering nicotine nor reinstated extinguished nicotine-seeking behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone produced a slow-onset moderate increase in extracellular DA. Pretreatment with R-MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the nucleus accumbens (NAc) in both naive and nicotine self-administrating rats, suggesting a DA-dependent mechanism underlying mitigation of nicotine''s effects. In conclusion, the present findings support further investigation of R-MOD for treatment of nicotine dependence in humans.     

Effect of oxymatrine on CaMKII expression in sciatic nerve ligation-induced neuropathic pain in mice北大核心CSCD

Aim To observe the analgesic effect of oxymatrine (OMT) and its mechanism. Methods A peripheral mononeuropathy was produced in adult mice by placing loosely constrictive ligatures around the common sciatic nerve. The antinociceptive effects of the OMT were assessed in mechanical allodynia and cold allodynia tests. The CAMKII inhibitor KN-93 and AIP were adopted to investigate the influence of OMT on the analgesic effect and analyze its analgesic mechanisms. Western blot was used to evaluate the expressions of tCaMKII and pCaMKII protein. Results The intraperitoneal administration of OMT (160, 80 mg · kg-1) increased the paw withdrawal threshold in the mechanical allodynia test (P < 0. 05), OMT (160, 80, 40 mg · kg-1 , ip) remarkably decreased the paw lifts in the cold allodynia test (P < 0. 05). Ith KN-93 (1. 25 (μg/site), AIP (0. 02 μg/site) significantly enhanced the analgesic effect of OMT (35 mg · kg-1) (P<0. 01). Protein expression of pCaMKII was decreased by OMT(160 mg · kg-1). Conclusion OMT has significant protective effects on chronic constriction injury(CCI) in mice, and the effective mechanism of OMT inhibits the expression of CaMKII receptor.     

Theoretical investigations on azole-fused tricyclic 1,2,3,4-tetrazine-2-oxides

Fused compounds, a unique class of large conjugate structures, have emerged as prime candidates over traditional nitrogen-rich mono-ring or poly-ring materials. Meanwhile, compounds containing catenated nitrogen chains have also attracted attention from scientists due to their high heats of formation. On the other hand, the azoxy [–N N(O)–] moiety has been found to increase density effectively in the molecular structure of compounds. Therefore, combining fused heterocyclic organic skeletons with the azoxy moiety can be regarded as an effective method for increasing the density and heat of formation, which results in substantial increase in detonation properties. Based on the above-mentioned considerations, in this study, a series of new non-hydrogen-containing 5/6/5 fused ring molecules with azoxy moiety structures are designed. Furthermore, their properties as potential high-energy-density materials, including their density, heats of formation, detonation properties, and impact sensitivity, have been extensively evaluated using thermodynamic calculations and density functional theory. Among the investigated compounds, 1,3,8,10-tetranitrodiimidazo[1,5-d:5′,1′-f][1,2,3,4]tetrazine 5-oxide (B), 1,10-dinitrobis([1,2,3]triazolo)[1,5-d:5′,1′-f][1,2,3,4]tetrazine 5-oxide (C) and 2,9-dinitrobis([1,2,4]triazolo)[1,5-d:5′,1′-f][1,2,3,4]tetrazine 5-oxide (D) display remarkable stabilities and are predicted to be high-performance energetic materials due to their high density (>1.94 g cm⁻³), detonation velocity (>9616 m s⁻¹), and detonation pressure (>41.1 GPa). In addition, our design strategy, which combines the azoxy moiety and fused tricyclic skeleton to construct nitrogen-rich molecular structures with high density and positive heat of formation, is a valuable approach for developing novel high-energy-density materials with excellent performance and stability.

In this work, a series of novel non-hydrogen-containing 5/6/5 fused ring molecules with azoxy moiety were designed, some physicochemical or detonation properties of them were calculated.     

对基层食品药品监管部门广告监测工作的认识和思考

目的:对基层食品药品监督管理部门广告监测工作的现状进行分析和梳理,为新形势下进一步做好该项工作做好准备。方法:分析基层广告监测工作的重要性、存在的主要问题,并提出了意见和建议。结果与结论:基层食品药品监管部门的广告监测工作非常重要,需要从完善法律法规、提高工作主动性、改进和探索工作方法等多方面予以改进,进一步提高基层食品药品违法广告监测工作的质量。