接触二甲基甲酰胺对男工生殖内分泌机能影响

目的研究二甲基甲酰胺(DMF)对男工生殖内分泌机能影响.方法按照国家标准测定作业场所空气中DMF浓度,并用尿中甲基甲酰胺(NMF)浓度来衡量作业工人实际接触水平,用化学发光免疫测定法(CLIA)测定了100名男工血清中卵泡刺激素(FSH)、黄体生成素(LH)、泌乳素(PRL)、睾酮(T)浓度.结果高水平DMF接触作业工人血清中T浓度[(30.15±8.37)g/L]高于低水平接触组[(25.36±10.69)g/L]和对照组[(18.56±8.07)g /L],而FSH浓度[(6.53±4.06)×10-3单位/L]则低于低水平接触组[(10.03±3.47)×10-3单位/L]和对照组[(12.63±6.55)×10-3单位/L];血清T浓度、异常率与DMF接触水平有明显剂量反应关系;高、低水平接触组 T/LH比值(3.72±2.06、3.41±2.55)明显低于对照组(7.75±10.16).结论 DMF能使男工FSH变化外,尚存在间质细胞功能及LH-T轴异常,对男工具有一定的生殖毒性.     

MTT法观察DMF致人肝细胞增殖抑制作用

目的观察不同染毒剂量二甲基甲酰胺(DMF)对正常成人离体肝细胞的增殖抑制作用。方法用MTT比色法观察细胞生长变化,分别以1.56mmol/L、6.25mmol/L、25mmol/L、100mmol/L DMF为染毒剂量,以6h、12h、24h为染毒时间对人肝细胞进行培养。比较在不同时间下,不同染毒剂量组与阴性组的细胞生长率。结果同一染毒时间组内,不同剂量组的细胞生长变化率结果差异有显著意义(F=27.41、23.86、111.22,P<0.01),以100mmol/L DMF组细胞增殖率为最低,但不同染毒剂量组细胞生长变化率未见明显剂量-效应关系,染毒6h和12h 25mmol/L组的细胞生长变化率高于其他浓度组;同一染毒剂量组内,各不同染毒时间组的细胞生长变化率结果差异有显著意义(F=27.80、29.79、42.47、28.88,P<0.01),以24h组细胞增殖率为最低。结论与阴性组比较,DMF对细胞增殖有抑制作用;但不同染毒剂量组细胞生长变化率的剂量-效应关系不明显;随染毒时间延长,同一染毒剂量组内细胞增殖活性变化率有下降趋势,有一定染毒时间-效应关系。     

顶空气相色谱法测定阿立哌唑中有机溶剂N,N-二甲基甲酰胺残留量

目的:建立测定阿立哌唑原料药中的有机溶剂N,N-二甲基甲酰胺(DMF)残留量的方法.方法:采用顶空气相色谱法,DB-624毛细管柱(30m×0.53mm,3μm),载气为氮气,流速20mL·min-1,柱温90℃;气化室温度160℃;氢火焰离子化检测器(FID)温度170℃.结果:在浓度范围9.32～1.19×103μg·mL-1内,线性关系良好,r=0.999 9,平均回收率为98.4%.最小检测浓度为4.7μg·mL-1.结论:本方法灵敏,精确,可靠,适用于测定阿立哌唑原料药中的有机溶剂DMF残留量.     

Neuroprotective effect of gold nanoparticles composites in Parkinson's disease model

Parkinson’s disease (PD) is second most common neurodegenerative disorder worldwide. Although drugs and surgery can relieve the symptoms of PD, these therapies are incapable of fundamentally treating the disease. For PD patients, over-expression of α-synuclein (SNCA) leads to the death of dopaminergic neurons. This process can be prevented by suppressing SNCA over-expression through RNA interference. Here, we successfully synthesized gold nanoparticles (GNP) composites (CTS@GNP-pDNA-NGF) via the combination of electrostatic adsorption and photochemical immobilization, which could load plasmid DNA (pDNA) and target specific cell types. GNP was transfected into cells via endocytosis to inhibiting the apoptosis of PC12 cells and dopaminergic neurons. Simultaneously, GNP composites are also used in PD models in vivo, and it can successfully cross the blood-brain barrier by contents of GNP in the mice brain. In general, all the works demonstrated that GNP composites have good therapeutic effects for PD models in vitro and in vivo.     

Nitrosamine Contamination in Pharmaceuticals: Threat,Impact, and Control

Nitrosamine-contaminated medicinal products have raised safety concerns towards the use of various drugs, not only valsartan and all tetrazole-containing angiotensin II receptor blockers, but also ranitidine, metformin, and other medicines, many of which have been recalled and prone to shortage. At any stages, from drug substance synthesis throughout each product's lifetime, these impurities may evolve if an amine reacts with a nitrosating agent coexisting under appropriate conditions. Consequently, drug regulatory authorities worldwide have established stringent guidelines on nitrosamine contamination for all drug products in the market. This review encompasses various critical elements contributing to successful control measures against current and upcoming nitrosamine issues, ranging from accumulated knowledge of their toxicity concerns and potential root causes, precise risk evaluation, as well as suitable analytical techniques with sufficient sensitivity for impurity determination. With all these tools equipped, the impact of nitrosamine contamination in pharmaceuticals should be mitigated. An evaluation aid to tackle challenges in risk identification, as well as suitable industry-friendly analytical techniques to determine nitrosamines and other mutagenic impurities, are among unmet needs that will significantly simplify the risk assessment process.     

Modification of the response of mouse skin to X-irradiation by a polar solvent,N,N-dimethylformamide

The modification of the response of mouse skin to either single or split (24 hrs) graded doses of X rays by topically applied N,N-dimethylformamide (DMF) was investigated. DMF was applied daily for 5 days prior to irradiation. At a radiation dose level producing dry desquamation, DMF enhanced the X ray response by a factor of 1.3. Also, at the same level of response, the fraction of X ray dose repaired in 24 hours was 0.57, whereas for the DMF-treated and irradiated skin, this factor was 0.41, indicating a reduction of about 28 % in subeffective damage repair. The times of maximal involvement of the skin reactions were not different in the X ray plus DMF treated mice versus mice receiving x-irradiation only. The data indicate that DMF is able to modify intrinsic radiation sensitivity of mouse skin epithelial cells, possibly through a reduction in the magnitude of the shoulder region of the survival curve.     

Application of N,N-dimethylformamide dineopentyl acetal for efficient anchoring of Nα-9-fluorenylmethyloxycarbonylamino-acids as p-alkoxybenzyl esters in solid-phase peptide synthesis

The attachment of Fmoc-amino acids onto p-alkoxybenzyl alcohol resins via DCC-DMAP coupling suffers from two different problems: formation of dimers and racemization. The use of N,N-dimethylformamide dineopentyl acetal for the preparation of Fmoc-aminoacyloxybenzyl handles is the basis of a safe and efficient anchoring method that avoids both problems.     

2011-2014年福建福鼎市合成革业二甲基甲酰胺职业危害现况

目的 通过对福建省福鼎市合成革企业二甲基甲酰胺(N,N-dimethylformamide,DMF)的哨点监测,研究宁德福鼎市合成革企业DMF危害暴露水平及其对接触人群健康状况的影响.方法 根据《福建省重点职业病哨点监测方案》调查合成革企业的基本情况[1],对福鼎市合成革企业涂台、配料、放布、收卷等存在DMF污染岗位的监测,并调查接触者基本情况,进行职业健康体检,每年体检人数约为1 500人.结果 2011-2014年福建省福鼎市合成革企业DMF总合格率较低为55.87％,不同岗位空气DMF浓度合格率分别为:配料岗位为41.07％,涂台岗位为34.53％,放布岗位为96.91％,收卷岗位为95.32％.不同年份ALT异常率2011年为11.10％,2012年为10.43％,2013年为9.63％,2014年为8.56％,2015年为4.94％.结论 福建省福鼎市合成革企业DMF合格率较低,尤其是配料和涂台两个工种DMF污染较重.DMF对工人肝功能的危害不容忽视,应密切关注作业点浓度[2-3],采取干预措施,保护接触人群职业健康.     

气相色谱法测定扎来普隆中二氯甲烷和N,N-二甲基甲酰胺的残留量

 目的建立毛细管气相色谱法测定扎来普隆中二氯甲烷和N,N-二甲基甲酰胺的残留量。方法采用DB-624熔融石英毛细管柱(30 m×0.32 mm,1.8μm);载气:氮气;分流比:60∶1。二氯甲烷的测定:以N,N-二甲基甲酰胺为溶剂;氯仿为内标;柱温:40℃,保持15 min,以40℃·min^-1的速率升温至180℃,保持10 min;气化室温度:180℃;检测器温度:200℃(FID)。N,N-二甲基甲酰胺的测定:以二氯甲烷为溶剂;甲苯为内标;柱温:85℃;气化室温度:200℃;检测器温度:200℃(FID)。结果二氯甲烷在15.02～150.2 mg·L^-1内线性关系良好,r=0.999 7(n=5),最低检出限为4.5 mg·L^-1,连续进样精密度RSD为1.8%,回收率为99.48%(RSD=0.9%)。N,N-二甲基甲酰胺在22.02～264.2 mg·L^-1内线性关系良好,r=0.999 7(n=5),最低检出限为4.4 mg·L^-1,连续进样精密度RSD为1.2%,回收率为99.55%(RSD=2.7%)。结论本方法可用于测定扎来普隆中二氯甲烷和N,N-二甲基甲酰胺的残留量。     

Aberrant expression of miRNA-192-5p contributes to N,N-dimethylformamide-induced hepatic apoptosis

Excessive exposure to N,N-dimethylformamide (DMF) can lead to occupational liver poisoning in workers; however, the underlying mechanism is not fully clarified. The importance of microRNAs (miRNAs) in chemical-induced hepatotoxicity has been demonstrated. To determine whether miRNAs are also involved in DMF-induced hepatotoxicity, we systematically analyzed the miRNA expression profiles in DMF-treated (75 and 150 mm ) HL-7702 liver cells and controls by high-throughput sequencing. Among the altered miRNAs, miR-192-5p was the most significantly upregulated in HL-7702 cells after DMF exposure and was involved in DMF-mediated cell apoptosis. By contrast, suppression of miR-192-5p in HL-7702 cells attenuated the apoptosis induced by DMF. Furthermore, the anti-apoptotic gene (NIN1/RPN12 binding protein 1 homolog [NOB1]) was predicted to be a potential miR-192-5p target according to bioinformatics analysis. The direct interaction between miR-192-5p and NOB1 was confirmed by the dual-luciferase activity assay in HEK293FT cells. Overexpression of miR-192-5p efficiently reduced NOB1 mRNA and protein expression in HL-7702 cells. Alteration in NOB1 expression influenced DMF-induced hepatotoxicity by affecting hepatic apoptosis. In addition, the inverse correlation between miR-192-5p expression levels and NOB1 expression was further confirmed in DMF-exposed mouse liver tissue samples. These observations demonstrated that promotion of apoptosis from the suppression of NOB1 by miR-192-5p overexpression was responsible for the DMF-induced hepatotoxicity. This work provides the molecular mechanism at the miRNA level for hepatic apoptosis induced by DMF.