高效液相色谱法测定甲硫氨酸维生素B1注射液中甲硫氨酸和维生素B1的含量

目的建立一种快速,准确的高效液相色谱法同时测定甲硫氨酸维生素B1注射液中甲硫氨酸和维生素B1的含量.方法采用C18柱 5μm(4.6 ×250mm),流动相为乙腈–0.5mol·L-1庚烷磺酸钠(20 80),检测波长为25nm.结果甲硫氨酸的线性范围是162.1～648.3μg·mL-1,r=0.9999,平均回收率为99.83%, RSD=0.485;维生素B1的线性范围是16.96～67.84μg·mL-1, r=0.9998,平均回收率为 99.17%,RSD=1.42.结论本方法可快速准确地检测甲硫氨酸维生素B1注射液中甲硫氨酸和维生素B1的含量     

叶酸及其代谢酶基因与宫颈癌相关性的研究综述

宫颈癌是常见的妇科恶性肿瘤之一,其发生发展是多因素共同作用的复杂过程。有研究显示,缺乏叶酸可能导致宫颈癌。MTHFR基因及MTRR基因是影响叶酸水平的重要因素,其编码的蛋白是叶酸代谢通路的关键酶。MTHFR是一种能将5,10-亚甲基四氢叶酸还原为5-甲基四氢叶酸的关键酶,维持着DNA的正常甲基化反应,这是叶酸代谢循环的主要形式。MTRR是一种辅助酶,有研究报道其基因多态性与癌症的发生具有相关性。但叶酸缺乏是否系宫颈鳞癌的致病因素或增加其易感性,现有的研究仍存在争议且尚无定论。因此,本文旨在对叶酸水平及参与其代谢的关键酶基因多态性与宫颈癌相关性的研究进展进行综述。     

Methionine restriction inhibits chemically-induced malignant transformation in the BALB/c 3T3 cell transformation assay

High consumption of red meat entails a higher risk of developing colorectal cancer. Methionine, which is more frequently a component of animal proteins, and folic acid are members of the one carbon cycle and as such important players in DNA methylation and cancer development. Therefore, dietary modifications involving altered methionine and folic acid content might inhibit colon cancer development. In the present study, the BALB/c 3T3 cell transformation assay was used to investigate whether methionine and folic acid are able to influence the malignant transformation of mouse fibroblasts after treatment with the known tumour initiator 3-methylcholanthrene. Three different methionine concentrations (representing a −40%, a “normal” and a +40% cell culture medium concentration, respectively) and two different folic acid concentrations (6 and 20 μM) were thereby investigated. Methionine restriction led to a decrease of type III foci, while enhancement of both methionine and folic acid did not significantly increase the cell transformation rate. Interestingly, the focus-lowering effect of methionine was only significant in conjunction with an elevated folic acid concentration. In summary, we conclude that the malignant transformation of mouse fibroblasts is influenced by methionine levels and that methionine restriction could be a possible approach to reduce cancer development.     

Identification of promising methionine aminopeptidase enzyme inhibitors: A combine study of comprehensive virtual screening and dynamics simulation study

Methionine aminopeptidase (MetAP) enzymes play a critical role in bacterial cell survival by cleaving formyl-methionine initiators at N-terminal of nascent protein, a process which is vital in proper protein folding. This makes MetAP an attractive and novel antibacterial target to unveil promising antibiotics. In this study, the crystal structure of R. prowazekii MetAP was used in structure-based virtual screening of drug libraries such as Asinex antibacterial library and Comprehensive Marine Natural Products Database (CMNPD) to identify promising lead molecules against the enzyme. This shortlisted three drug molecules; BDE-25098678, BDE-30686468 and BDD_25351157 as most potent leads that showed strong binding to the MetAP enzyme. The static docked conformation of the compounds to the MetAP was reevaluated in molecular dynamics simulation studies. The analysis observed the docked complexes as stable structure with no major local or global deviations noticed. These findings suggest the formation of strong intermolecular docked complexes, which showed stable dynamics and atomic level interactions network. The binding free energy analysis predicted net MMGBSA energy of complexes as: BDE-25098678 (-73.41 kcal/mol), BDE-30686468 (-59.93 kcal/mol), and BDD_25351157 (-75.39 kcal/mol). In case of MMPBSA, the complexes net binding energy was as; BDE-25098678 (-77.47 kcal/mol), BDE-30686468 (-69.47 kcal/mol), and BDD_25351157 (-75.6 kcal/mol). Further, the compounds were predicted to follow the famous Lipinski rule of five and have non-toxic, non-carcinogenic and non-mutagenic profile. The screened compounds might be used in experimental test to highlight the real anti- R. prowazekii MetAP activity.     

Urinary homocystine levels in a newborn infant with cystathionine synthase deficiency

A boy with homocystinuria due to cystathionine synthase deficiency was found to have hypermethioninaemia by neonatal blood screening, but was not diagnosed as homocystinuric until 3 months of age because urinary homocystine was not detected by the cyanidenitroprusside test or on two examinations with a sensitive amino acid autoanalyser. These findings indicate that tests for urinary homocystine should be made repeatedly with an amino acid auto-analyser in newborn infants with hypermethioninaemia until the enzyme defect is identified.     

蛋氨酸对大鼠胚胎发育影响的研究

研究蛋氨酸对孕９．５－１１．５ｄ大鼠胚胎发育的影响,方法：取孕９．５ｄ的大鼠胚胎,分别用蛋氨酸含量较低的纯牛血清和蛋氨酸＋牛血清为实验组,用大鼠血清做为对照组,在体外培养４８ｈ,并用Ｋｌｕｇ等人的评分系统对胚胎生长发育和形态进行评分,结果：在牛血清中培养的胚胎,其卵黄囊血循环、生长参数和蛋白质含量均低于牛血清＋蛋氨酸培养组,各器官发育异常率均高于牛血清＋蛋白氨酸培养组,加入蛋氨酸后,可以明显地改善     

Plasma homocysteine concentrations and the single nucleotide polymorphisms in the methionine synthase gene (MTR 2756A>G): Associations with the polycystic ovary syndrome An observational study

BACKGROUND: Elevated plasma homocysteine (Hcy) is a recognized risk factor for cardiovascular disease (CVD) and other defects. Biochemical and genetic studies have characterized molecular determinants contributing to alter Hcy metabolism. The vitamin B12 dependent enzyme methionine synthase (MTR) regulates de novo production of methionine from homocysteine. Defects in the activity of this enzyme may possibly predispose to higher plasma Hcy concentrations. STUDY DESIGN: We examined the associations between plasma Hcy concentrations and a single nucleotide polymorphism (SNP) in the MTR gene (MTR 2756A>G), and plasma folate concentrations, in 71 women (Caucasian and South Asian) attending a fertility clinic. We also determined the ethnic variations in the frequencies of the 3 genotypes of the MTR 2756 A>G gene. RESULTS: The frequency of the variant G allele was similar in the Caucasians and the South Asians (OR: 1.83; 95% CI: 0.79-4.23, p=0.2). The frequency was also similar in the PCOS and non-PCOS groups (OR: 0.88; 95% CI: 0.39-1.99). Plasma Hcy levels were significantly higher in women with PCOS compared with non-PCOS controls (p=0.05) and in Caucasian women with PCOS compared with Caucasian controls (p=0.04) in the presence of the MTR 2756 AA genotype (wild type). After adjusting for age, BMI, waist circumference and ethnicity, the significant predictors of plasma Hcy concentrations were plasma LDL, whole blood folate concentrations and a clinical diagnosis of PCOS. CONCLUSIONS: The important predictors of plasma Hcy concentration in women of reproductive age are whole blood folate concentrations, a background of PCOS and plasma LDL concentrations. The SNP 2756 A>G in the MTR gene does not appear to influence the plasma Hcy levels.     

D-甲硫氨酸联合化疗药物诱导胃癌细胞凋亡的实验研究

目的探讨甲硫氨酸(Met)及其联合化疗药物对胃癌细胞凋亡的诱导作用。方法将人胃癌细胞株SGC-7901分别置于6种不同培养液:含L-Met、含D-Met、不含Met而替以同型半胱氨酸(Met-Hcy )或在上述培养液中分别加入氟尿嘧啶(5-Fu)。培养48h后,应用流式细胞仪检测细胞凋亡率及凋亡相关基因bcl-2和bax的表达,并在电镜下观察细胞形态变化。结果无论是否加入化疗药物,D-Met组的细胞凋亡率均高于Met-Hcy 组和L-Met组;L-Met加5-Fu组的细胞凋亡率显著高于L-Met组和Met-Hcy 组,但与D-Met组差异无显著性意义。各组间的bcl-2和bax表达率无改变。结论D-Met及D-Met联合化疗药物可通过诱导胃癌细胞凋亡而抑制肿瘤生长,作用机制可能与bcl-2和bax的表达无关。     

18F-FDG与11C-MET PET显像在神经上皮性肿瘤术前分级中的价值及与Ki67相关性的比较

目的 比较^18F-脱氧葡萄糖（FDG）与^11C-蛋氨酸（MET）PET显像在神经上皮性肿瘤术前分级中的价值及与细胞增殖指标Ki67的相关性。方法 39例经病理检查证实的神经上皮性肿瘤患者分别行^18F-FDG、^11C-MET PET检查，均进行视觉分析和半定量分析，并与病理分级和Ki67标记指数（u）比较，进行统计学分析。结果 视觉分级：23例高级别肿瘤患者中有22例呈^18F-FDG高代谢，16例低级别肿瘤患者中有14例呈^18F-FDG中、低代谢；39例患者中除1例低级别肿瘤表现为^11C-MET低代谢外，其余均为^11C-MET高代谢。半定量分析：^18F-FDG结果显示，除Ⅰ级与Ⅱ级肿瘤问无统计学差异外，其余各级间差异均有显著性（P〈0．05）；^11C-MET结果显示，只有Ⅱ级与Ⅳ级肿瘤间差异有显著性（P〈0．01），其余各级间均无统计学差异。^18F-FDG与^11C-MET的摄取均与Ki67LI呈显著正相关，^11C-MET的相关性强于^18F—FDG。且Ⅱ、Ⅲ级肿瘤内^11C-MET的摄取与Ki67LI亦相关，而^18F-FDG在各级肿瘤内与Ki67LI均无相关性。结论 ^18F—FDG的视觉及半定量分级均优于^11C-MET；^11C-MET有助于低级别肿瘤的检出和边界描绘，且^11C-MET的代谢活性更能体现肿瘤细胞的增殖特性。     

HPLC法测定注射用甲硫氨酸维B_1有关物质

目的:测定注射用甲硫氨酸维B_1中有关物质的方法。方法:采用高效液相色谱法,色谱柱C_(18)ODS-1,Kromasil,4.6mm×250mm,流动相为甲醇-乙腈-0.020mol/L庚烷磺酸钠溶液(含1%三乙胺溶液)(用磷酸调pH值至5.5)(9:9:82)。检测波长:220nm,流速1mL/min。结果:甲硫氨酸与维B_1及其二者降解产物能有效分离,甲硫氨酸最低检出量为22ng,维生素B_1最低检出量为10ng,注射用甲硫氨酸维B_1成品控制总杂质不超过1.5%。结论:本法准确、简便、专属,适用于注射用甲硫氨酸维B_1的有关物质检查。