Syntheses, structures and properties of copper(II) complexes containing N-(2-hydroxybenzyl)-amino amide ligands

Four copper(II) complexes containing the reduced Schiff base ligands, namely, N-(2-hydroxybenzyl)-glycinamide (Hsglym) and N-(2-hydroxybenzyl)-l-alaninamide (Hsalam) have been synthesized and characterized. The crystal structures of [Cu₂(sglym)₂Cl₂] (1), [Cu₂(salam)₂(NO₃)₂] · H₂O (3), [Cu₂(salam)₂(NO₃)(H₂O)](NO₃) · 1.5H₂O (4), [Cu₂(salam)₂](ClO₄)₂ · 2H₂O (5) show that the Cu(II) atoms are bridged by two phenolato oxygen atoms in the dimers. The sglym ligand bonded to Cu(II) in facial manner while salam ligand prefers to bind to Cu(II) in meridonal geometry. Variable temperature magnetic studies of 3 showed it is antiferromagnetic. These Cu(II) complexes and [Cu₂(sglym)₂(NO₃)₂] (2), exhibit very small catecholase activity as compared to the corresponding complexes containing acid functional groups.     

Methods for Identifying a Default Cross-Species Scaling Factor

The need to identify “toxicologically equivalent” doses across different species is a major issue in toxicology and risk assessment. In this article, we describe an approach for establishing default cross-species extrapolation factors used to scale oral doses across species for non-carcinogenic endpoints. This work represents part of an on-going effort to harmonize the way animal data are evaluated for carcinogenic and non-carcinogenic endpoints. In addition to considering default scaling factors, we also discuss how chemical-specific data (e.g., metabolic or mechanistic data) can be incorporated into the dose extrapolation process. After first examining the required properties of a default scaling methodology, we consider scaling approaches based on empirical relationships observed for particular classes of compounds and also more theoretical approaches based on general physiological principles (i.e, allometry). The available data suggest that the empirical and allometric approaches each provide support for the idea that toxicological risks are approximately equal when daily oral doses are proportional to body weight raised to the 3/4-power. We also discuss specific challenges for dose scaling related to different routes of exposure, acute versus chronic toxicity, and extrapolations related to particular life stages (e.g., childhood).     

Dosimetric impact of Acuros XB on cervix radiotherapy using RapidArc technique: a dosimetric study

BackgroundAcuros XB (AXB) may predict better rectal toxicities and treatment outcomes in cervix carcinoma. The aim of the study was to quantify the potential impact of AXB computations on the cervix radiotherapy using the RapidArc (RA ) technique as compared to anisotropic analytical algorithm (AA) computations.Materials and methodsA cohort of 30 patients previously cared for cervix carcinoma (stages II–IIIB) was selected for the present analysis. The RA plans were computed using AA and AXB dose computation engines under identical beam setup and MLC pattern.ResultsThere was no significant (p > 0.05) difference in D_95% and D_98% to the planning target volume (PTV); moreover, a significant (p < 0.05) rise was noticed for mean dose to the PTV (0.26%), D_50% (0.26%), D_2% (0.80%) and V_110% (44.24%) for AXB computation as compared to AA computations. Further, AXB estimated a significantly (p < 0.05) lower value for maximum and minimum dose to the PTV. Additionally, there was a significant (p < 0.05) reduction observed in mean dose to organs at risk (OARs) for AXB computation as compared to AA, though the reduction in mean dose was non-significant (p > 0.05) for the rectum. The maximum difference observed was 4.78% for the rectum V_50Gy, 1.72%, 1.15% in mean dose and 2.22%, 1.48% in D_2% of the left femur and right femur, respectively, between AA and AXB dose estimations.ConclusionFor similar target coverage, there were significant differences observed between the AAA and AXB computations. AA underestimates the V_50Gy of the rectum and overestimates the mean dose and D_2% for femoral heads as compared to AXB. Therefore, the use of AXB in the case of cervix carcinoma may predict better rectal toxicities and treatment outcomes in cervix carcinoma using the RA technique.     

两种盲蝽的抗药性监测

本文从2009到2011年连续3年用马拉硫磷、毒死蜱、灭多威、三氟氯氰菊酯、吡虫啉、硫丹6种杀虫药剂诊断剂量监测了河北、河南、山东、安徽等重要棉产区绿盲蝽Apolygus lucorum(Meyer-Dür)田间种群的抗药性。2010年马拉硫磷诊断剂量处理河北邱县、安徽望江田间种群死亡率95%以上;毒死蜱诊断剂量河南郑州、山东滨州,安徽地区的田间绿盲蝽死亡率大于80%;三氟氯氰菊酯诊断剂量死亡率接近95%以上;2010年安徽望江、2011年河北邱县、山东滨州、安徽无为田间种群在吡虫啉诊断剂量下的死亡率在78%～90%。点滴法对2011年各地绿盲蝽种群抗药性监测表明,各地绿盲蝽对毒死蜱、灭多威、吡虫啉均处于敏感阶段,对于马拉硫磷、三氟氯氰菊酯、硫丹大多处于低抗水平阶段。在对中黑盲蝽Adelphocoris suturalis Jakovlev3年的抗性监测中,作者发现种群抗性个体频率的出现更为普遍。     

Involvement of p53 in gemcitabine mediated cytotoxicity and radiosensitivity in breast cancer cell lines

Gemcitabine (2',2'-difluoro-2'-deoxycytidine; dFdCyd) is one of the anti-metabolites drugs that target DNA replication. We evaluated dFdCyd cytotoxicity and its radiosensitizing ability in human breast cancer cell lines, MCF-7 (wild-type p53) and MDA-MB-231 (mutant-type p53) along with normal mammary epithelial cell line (MCF-12) for comparison. Radiosensitivity and cytotoxicity were measured by the clonogenic survival assays. DNA DSBs was studied by Pulse Field Gel Electrophoresis (PFGE) and cell cycle distribution was analyzed by flow cytometry. MDA-MB-231 cells were the most sensitive to the cytotoxicity of dFdCyd (IC(50) 5 nM) then MCF-7 (IC(50) 10nM), whereas MCF-12 cells were the most resistant to the cytotoxicity of dFdCyd (IC(50) 70 nM). MCF-12 and MCF-7 cell lines did not show any radiosensitization to dFdCyd, whereas the MDA-MB-231 cells showed significantly increased radioresistant to dFdCyd at equimolar concentration (p=0.002) and at IC(50) concentration (p<0.001). The DNA double strand breaks (DSBs) repair showed that dFdCyd neither increases DNA DSBs nor decreases the rate of their repair in MCF-12 and MCF-7 cell lines, while the same treatment in MDA-MB-231 cell line led to decrease the rate of DSBs or increase the rate of DNA repair (p=0.034). Therefore, dFdCyd is a cytotoxic agent, especially in the cancer cells irrespective of having wild-type or mutated p53 protein, but it is not effective as radiosensitizer in the cell lines used in this study. dFdCyd combined with radiation reduces the efficacy of chemo-radiotherapy in p53 mutated cells. Therefore, p53-mutated cancer could be a counter-indication for radiation-gemcitabine combined treatment.     

The associations of IL-18 serum levels and promoter polymorphism with tacrolimus pharmacokinetics and hepatic allograft dysfunction in Chinese liver transplantation recipients

Interleukin 18 (IL-18) is a potent proinflammatory cytokine, which promotes the secretions of TNF-α, IL-1β, IL-2 and IFN-γ. All those inflammatory cytokines can influence the CYP450 and MDR dependent drug disposition. On the other side, those cytokines can induce hepatic allograft dysfunction. We investigated the effects of serum IL-18 and IL-18 gene promoter polymorphisms on tacrolimus pharmacokinetics and hepatic allograft dysfunction in liver transplant recipients. A total of 155 liver transplant recipients were enrolled into this study (34 females and 121 males). The mean follow-up was 52 months (range 16-96 months).The total liver transplant recipients were divided into hepatic allograft dysfunction (N = 14) and no hepatic allograft dysfunction (N = 141). We studied two single-nucleotide polymorphisms in the promoter region of IL-18 gene at the position G-137C (rs187238) and A-607C (rs1946518) by HRM analysis (high-resolution melting curve analysis). Tacrolimus dosage, tacrolimus blood concentration, serum levels of IL-18 and IFN-γ were also investigated. We found the recipients with higher IL-18 and IFN-γ serum levels had lower tacrolimus concentration/dose (C/D) ratios (P < 0.05). In the mean time, after transplantation hepatic allograft dysfunction was more likely to happen to those recipients. However, there was no significant difference in the frequencies of A-607C and G-137C allelic distribution in recipients' tacrolimus concentration/dose (C/D) ratios. This study identifies IL-18 reduced tacrolimus concentration/dose (C/D) ratio through up regulation of P-glycoprotein (P-gp).     

Systematic assessment of reduced representation bisulfite sequencing to human blood samples: A promising method for large-sample-scale epigenomic studies

Complementary to the time- and cost-intensive direct bisulfite sequencing, we applied reduced representation bisulfite sequencing (RRBS) to the human peripheral blood mononuclear cells (PBMC) from YH, the Asian individual whose genome and epigenome has been deciphered in the YH project and systematically assessed the genomic coverage, coverage depth and reproducibility of this technology as well as the concordance of DNA methylation levels measured by RRBS and direct bisulfite sequencing for the detected CpG sites. Our result suggests that RRBS can cover more than half of CpG islands and promoter regions with a good coverage depth and the proportion of the CpG sites covered by the biological replicates reaches 80-90%, indicating good reproducibility. Given a smaller data quantity, RRBS enjoys much better coverage depth than direct bisulfite sequencing and the concordance of DNA methylation levels between the two methods is high. It can be concluded that RRBS is a time and cost-effective sequencing method for unbiased DNA methylation profiling of CpG islands and promoter regions in a genome-wide scale and it is the method of choice to assay certain genomic regions for multiple samples in a rapid way.     

Terrorist Radiological Dispersive Device (RDD) Scenario and Cancer Risk Assessment

Terrorist attacks using radiological dispersal devices (RDD) are important threats that can lead to major environmental, economic, and public health concerns. In a simulation using a Gaussian model, we sought to determine dose curves as a function of distance from the explosion core site and from these data to determine the relative risk of developing tumors as well as the probability of causation (i.e., the statistical correlation between occurrence of malignancies and previous exposure to radiation). Calculation confirmed the cause dependence on age at exposure and the probability of tumor causation. This study aimed at emphasizing the importance of responding rapidly and efficiently, with a user-friendly user methodology that initially may help to guide the response from basic actions to the complete decision process.