Determination and Risk Assessment of Six Hepatotoxic Pyrrolizidine Alkaloids in Verbenae Herba / 中国实验方剂学杂志

Objective:To establish ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） for simultaneous determination of six hepatotoxic pyrrolizidine alkaloids in Verbenae Herba， and to carry out preliminary risk assessment according to the research results. Method:An ACQUITY UPLC HSS T3 column （2.1 mm×100 mm， 1.8 μm） was used for analysis with 0.05% formic acid and 2.5 mmol·L^-1 ammonium formate in water （A）-0.05% formic acid and 2.5 mmol·L^-1 ammonium formate in acetonitrile （B） as mobile phase for gradient elution （0-12 min， 3%-8%B； 12-25 min， 8%-15%B； 25-26 min， 15%-3%B； 26-30 min， 3%B）， the flow rate was 0.3 mL·min^-1， the column temperature was 40 ℃， and the injection volume was 1 μL. MS system was operated by electrospray ionization （ESI） in the positive ion mode with multiple reaction monitoring mode. MS parameters of triple quadrupole and six analytes were optimized for qualitative and quantitative analysis. According to the determination results， the risk assessment was carried out by using margin of exposure （MOE） combined with transfer rate of hot water extraction. Result:Based on the instrument precision， linear range， repeatability， stability， recovery and other methodological validations， the results were in conformity with relevant standards of quantitative analysis. The linear ranges of intermedine， lycopsamine， intermedine <italic>N</italic>-oxide， lycopsamine<italic> N</italic>-oxide， echimidine<italic> N</italic>-oxide and echimidine were good （<italic>r</italic>≥0.999 0） between peak area and mass concentration in the ranges of 0.984-49.20， 0.994-49.70， 1.012-50.60， 1.032-51.60， 1.004-50.20， 1.016-50.80 µg·L^-1， respectively. The average recoveries of these six analytes were 87.2%-94.2% with relative standard deviation （RSD）<4.0%. Their MOE values were >10 000. Conclusion:The UPLC-MS/MS established in this study is stable and feasible， which can provide scientific basis for the quality control and safety evaluation of hepatotoxic pyrrolizidine alkaloids in Verbenae Herba.

A review of existing strategies for designing long-acting parenteral formulations: Focus on underlying mechanisms, and future perspectives

The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations (LAPFs) with the aim of improving drug pharmacokinetics and therapeutic efficacy. LAPFs have been proven to extend the half-life of therapeutics, as well as to improve patient adherence; consequently, this enhances the outcome of therapy positively. Over past decades, considerable progress has been made in designing effective LAPFs in both preclinical and clinical settings. Here we review the latest advances of LAPFs in preclinical and clinical stages, focusing on the strategies and underlying mechanisms for achieving long acting. Existing strategies are classified into manipulation of

Virtual screening of natural and synthetic inhibitors of cyclooxygenase COX-2 enzyme using docking-scoring functions

In this paper, theoretical elucidation of cyclooxygenase interaction with synthetic and natural bioactive moleculesusing molecular docking is studied with molecular docking implicating solvation parameters. Obtained results showthat synthetics and natural inhibitors of thym interact differently with cyclooxygenase inflammation enzyme afterincluding solvatation parameter and confirm primary studies concerning the anti-inflammatory effect. We concludethat the solvatation parameter must be taken into account in all molecular docking studies because of different resultswhich permits a better comprehension of the inhibition process and more clear ideas to develop new drugs. Resultsallow us to propose chlorogenique as a novel molecule to be developed into a new novel drug

Analysis and health risk assessment of aflatoxin B_1 residue in Ziziphi Spinosae Semen / 中国中药杂志

This study aimed to analyze the residues of aflatoxin B_1( AFB_1) in Ziziphi Spinosae Semen from different producing areas and to assess the health risk of aflatoxin B_1 residue based on the obtained data. A total of 72 samples of Ziziphi Spinosae Semen from different areas were detected by IAC-HPLC-FLD. Based on the data of AFB_1 pollution,a probabilistic assessment model with Monte Carlo simulation was developed. Then,the risk assessment of AFB_1 exposure by Ziziphi Spinosae Semen intake was carried out by MOE( margin of exposure). The results showed that 32 out of 72 of samples( 44. 4%) were found to be contaminated with AFB_1,and the average and maximum concentration of AFB_1 in samples was 5. 42 μg·kg~(-1) and 55. 09 μg·kg~(-1),respectively. After health risk assessment,the average and 97. 5%( 90% confidence interval) exposure level of daily exposure of AFB_1 by Ziziphi Spinosae Semen intake were 0. 008 6( 0. 008 1-0. 009 2) and 0. 057 3( 0. 053 2-0. 061 4) μg·kg~(-1)·d~(-1),respectively. The results showed common use of Ziziphi Spinosae Semen had low level of risk associated with AFB_1. However,the high consumption of Ziziphi Spinosae Semen showed a higher risk than common intake,requiring attention. This study laid a foundation for clinical safe prescription of Ziziphi Spinosae Semen.

Homology modeling and application of 3 D structure of Cav1.2 channel / 中国药理学通报

Aim To construct 3 D structure model of cardiac Cav1.2 channel and check its accuracy and re-liability.Methods Homology model of Cav1.2 chan-nel α1 subunit was constructed using SWISS-MODEL server.The model was submitted to an online testing server built by University of California and scored by it.The binding of Cav1.2 channel with blocker or drug was simulated by MOE software molecular docking pro-gram to check the model′s accuracy and reliability.Re-sults Both the target sequence Cav1.2 α1 C and the template sequence Cav1.1 α1 S searched by SWISS-MODEL server belonged to L-type Ca2+channel.Since the homology was 7 1.5% revealed by sequence align-ment,homology modeling was performed using automa-ted mode.L-type Ca2+ channel blockers Verapamil, Nifedipine and Diltiazem could bind to the 3 D structure model of Cav1.2 channel,while sodium channel bloc-ker TTX could not.Furthermore,active ingredient of traditional Chinese drug Praeruptorin A and Berberine could also bind to the 3D structure model of Cav1.2 channel.Conclusion The 3 D structure model of Cav1.2 channel was constructed successfully,which provides reliable materials for further studies and estab-lishes the foundation for the application of homology modeling in the study of 3 D structure prediction of ion channels.

Estimate of dietary intake of chloropropanols (3-MCPD and 1, 3-DCP) and health risk assessment / Estimativa da ingestão de cloropropanóis (3-MCPD e 1,3-DCP) e avaliação do risco à saúde

Chloropropanols, including 3-monochloropropane-1,2-diol (3-MCPD) and 1,3-dichloropropan-2-ol (1,3-DCP), comprise a group of chemicalcontaminants with carcinogenic and genotoxic properties. They have been found in a variety of processed foods and food ingredients, suchas hydrolyzed vegetable protein, soy sauce, cereal-based products, malt-derived ingredients, and smoked foods. This study aimed to assessthe dietary exposure to 3-MCPD and 1,3-DCP in Brazil and verify whether the presence of these substances in foods could represent healthrisks. The intake was calculated by combining data on food consumption, provided by the Consumer Expenditure Survey 2008-2009, withthe levels of contaminant occurrence determined by gas chromatography-mass spectrometry. The exposure to 3-MCPD ranged from 0.06 to0.51 µg.kg bw–1.day–1 considering average and high consumers, while the intake of 1,3-DCP was estimated to be 0.0036 µg.kg bw–1.day–1 inthe worst case scenario evaluated. Based on these results, it was verified that the Brazilians’ exposure to chloropropanols does not present asignificant health risk. However, the consumption of specific foods containing high levels of 3-MCPD could exceed the provisional maximumtolerable daily intake of 2 μg.kg bw–1 established for this compound and, therefore, represent a potential concern.

Os cloropropanóis, entre eles o 3-monocloropropano-1,2-diol (3-MCPD) e o 1,3-dicloropropan-2-ol (1,3-DCP), compreendem um grupo de contaminantes químicos com propriedades carcinogênicas e genotóxicas, encontrados em diversos alimentos processados e ingredientes alimentícios, como proteína vegetal hidrolisada, molho de soja, produtos à base de cereais, ingredientes derivados de malte e alimentos defumados. Este trabalho teve como objetivo avaliar a exposição ao 3-MCPD e 1,3-DCP pela dieta no Brasil e verificar se a presença destes compostos em alimentos pode representar um risco à saúde da população. A ingestão foi calculada combinando-se dados sobre o consumo alimentar, fornecidos pela Pesquisa de Orçamento Familiares 2008-2009, com os níveis de ocorrência dos contaminantes, determinados por cromatografia gasosa – espectrometria de massas. A exposição ao 3-MCPD variou de 0,06 a 0,51 µg.kg pc–1.dia–1 considerando médios e grandes consumidores, enquanto que a ingestão de 1,3-DCP foi estimada em 0,0036 µg.kg pc–1.dia–1 no pior cenário avaliado. Com base nesses resultados, verificou-se que a exposição aos cloropropanóis não representa um risco significativo à saúde da população brasileira.Entretanto, o consumo de determinados alimentos contendo altos níveis de 3-MCPD poderia ultrapassar a ingestão diária máxima tolerável provisória de 2 μg.kg pc–1 estabelecida para este composto e, assim, representar uma preocupação potencial.

History of Spinal Deformity Surgery Part II: The Modern Era

Following Dwyer introduction of anterior spinal instrumented fusion surgery, Zielke, Moss-Miami, and Kaneda had made a significant progression on anterior spinal instrumented fusion which allowed excellent correction without significant loss of correction or implant failure. King and Moe deveoped classification of thoracic major curve following Harrington rod intrumentation. King classification presented a stable vertebra concept and selective fusion concept. Surgical classification of Adolescent Idiopathic Scoliosis (AIS) developed by Harms study group provided a more sophisticated two dimensional understanding of curve nature. Surgical intervention of adult scoliosis and sagittal imbalance is still challenging and evolving. Several evidences such as sacropelvic fixation and bone morphogenetic protein helped us to deal with adult deformity. The surgical decision making on spinal deformity surgery is still yet evolving.