N—氧化利福平对照品结晶的制备与分析鉴定

利福平是一种半合成抗生素。成品中存在多种杂质,N-氧化利福平是其中的一种,N-氧化利福平分子中氧化的确切位置未见报道。本文报道了N-氧化利福平的制备、重结晶和测试了TLC、 NMR、UV、IR、质谱等理化常数,确证了N-氧化利福平分子中N-氧化的位置,N-氧化利福平抗菌活性仅为利福平的0.8％,其毒性小于利福平。     

GC-MS/MS测定头孢菌素类药物中8种N-亚硝胺类基因毒性杂质

目的:建立GC-MS/MS法测定头孢孟多酯钠、头孢地嗪钠、盐酸头孢替安中8种N-亚硝胺类杂质(N-亚硝基二甲胺、N-亚硝基二乙胺、N-亚硝基二丙胺、N-亚硝基二丁胺、N-亚硝基甲基乙基胺、N-亚硝基吡咯烷、N-亚硝基哌啶、N-亚硝基吗啉).方法:采用VF-WAX ms色谱柱(30 m×0.25 mm,膜厚0.25 μm...     

UPLC-MS/MS法同时测定氯沙坦钾和缬沙坦中7个亚硝胺类基因毒性杂质

目的:建立超高效液相色谱-串联质谱法(UPLC-MS/MS)同时测定氯沙坦钾和缬沙坦中7个基因毒性杂质(N-亚硝基二甲胺、N-亚硝基-4-甲基-4-氨基丁酸、N-亚硝基二乙胺、N-亚硝基乙基异丙基胺、N-亚硝基二异丙胺、N-亚硝基二丙胺、NN-亚硝基二丁胺).方法:采用Agilent Infinity Lab Poro...     

N-钙黏蛋白在胃癌组织中的表达

目的探讨N-钙黏蛋白在胃癌组织中的表达情况及其与临床病理特征及预后的关系。方法采用免疫组织化学PV-9005法检测143例胃癌组织中N-钙黏蛋白的表达。通过χ2分析、Kaplan-Meier方法和多因素生存分析,对N-钙黏蛋白和患者的临床病理特征之间的关系及预后进行分析。结果 N-钙黏蛋白在16例胃癌组织中呈阳性表达。N-钙黏蛋白在胃癌组织中的表达与患者肿瘤分期、低分化、静脉转移、肝转移和复发相关,差异有统计学意义(P<0.05)。Kap-lan-Meier方法表明,年龄、N-钙黏蛋白阳性、淋巴结转移、肝转移与预后相关。但是多因素生存分析显示,仅N-钙黏蛋白的表达和肝转移是独立的预后因子。结论 N-钙黏蛋白可作为胃癌的独立预后因子,预示患者预后不良。此外,患者的年龄、肿瘤分期、低分化、静脉转移、肝转移和复发具有相关性。     

化妆品中N-亚硝胺类化合物的安全风险

本文围绕化妆品中N-亚硝胺类化合物的来源、国外的研究基础和应对措施以及我国关于化妆品中N-亚硝胺类化合物的管理规定和检测方法等进行阐述,提出加强化妆品中N-亚硝胺类化合物风险管理的建议和措施.     

基因工程单克隆抗体N-端氨基酸序列的测定

目的:建立了具有焦谷氨酸封闭N-端的重组抗体N-端氨基酸序列分析方法。方法:利用高温稳定的焦谷氨酸肽酶,基因工程重组单抗样品在高温变性条件下,去除其N-端焦谷氨酸封闭。经还原SDS-PAGE和电印迹后,进行N-端氨基酸序列测定,并与电印迹后在PVDF膜上去封闭处理效果进行比较。结果:测定了17种基因工程单克隆抗体,其中有7个为重链去封闭处理后再进行测序的抗体样品,用2种方法都可顺利去除N-端封闭的焦谷氨酸,从而进行N-端氨基酸序列测定;如果不进行去封闭处理,部分样品无法进行N-端氨基酸序列测定。结论:2种方法都适于N-端具有焦谷氨酸封闭单抗的氨基酸序列分析。     

高效液相色谱-串联质谱法同时测定3种N-亚硝胺类基因毒性杂质

目的 建立高效液相色谱-串联质谱(HPLC-MS/MS)法同时测定厄贝沙坦原料药中3种N-亚硝胺类基因毒性杂质(N-亚硝基乙基异丙胺、N-亚硝基二异丙胺和N-亚硝基二丁胺)。方法 采用Agilent 120 PFP色谱柱(100 mm×2.1 mm, 2.7μm),流动相为甲醇(A)-0.1%甲酸(B),梯度洗脱,流速0.4 mL·min^-1,柱温40℃;采集模式为正离子,监测模式为质谱多反应监测。结果 N-亚硝基乙基异丙胺、N-亚硝基二异丙胺和N-亚硝基二丁胺在各自线性范围内线性关系良好(R²≥0.999 7),平均加样回收率分别为95.13%,92.00%和93.96%,RSD分别为4.22%,3.25%和3.60%。结论 该方法简单、快速,灵敏度高,准确性强,重复性好,可用于厄贝沙坦原料药中N-亚硝胺类基因毒性杂质的检测。     

N-杂环卡宾催化的成环反应研究进展

目的 介绍N-杂环卡宾催化的成环反应研究进展。方法 综合国内外报道的文献,阐述N-杂环卡宾催化的成环反应。结果 列出了N-杂环卡宾催化的分子内Stetter反应、亲核取代反应、环加成反应和串联反应等成环方法,重点分析了N-杂环卡宾催化的[4+2],[3+2],[2+2]和[3+3]环加成合成法。结论 N-杂环卡宾催化成环反应的发展在有机合成方法学中为高效成环提供了新的途径和策略。     

NMDA受体及其拮抗剂的研究进展

N-甲基-D-天冬氨酸(NMDA)受体是一种离子型谷氨酸受体,在中枢神经系统兴奋性的突触传递、可塑性和兴奋毒性中起着关键作用,与机体的记忆、学习和情绪密切相关.本文从结构分布和生理活性这两方面详细总结了N-甲基-D-天冬氨酸受体各亚型的特点,介绍并汇总了目前研究较多的N-甲基-D-天冬氨酸受体拮抗剂,为N-甲基-D-天...     

单酰胺菌素的酶酰化作用

单酰胺菌素是从细菌中分离出来的一类新的单环β-内酰胺抗生素,它们是3-氨基单菌胺酸的N-酰基衍生物.正如青霉素和头孢菌素一样,N-酰基的性质影响它们的抗菌活性.青霉素和头孢菌素的N-酰化作用能用酶法和化学法完成.本文报道用大肠杆菌的青霉素酰基转移酶生产各种N-酰基单酰胺菌素.从大肠杆菌中纯化苄青霉素酰基转移酶     

Tissue-specific regulation of insulin-like growth factors and insulin-like growth factor binding proteins in male diabetic rats in vivo and in vitro

1. Insulin-like growth factors (IGFs) are associated with the development of diabetes mellitus. The liver, kidney and heart have been implicated as important organs in the onset of diabetes mellitus. However, the effect of diabetes on the IGF system in these organs has not been fully described. Thus, we investigated changes in IGF-I, IGF-II and IGF binding proteins (IGFBPs) in male steptozotocin-induced diabetic rats, as well as in a high glucose-induced in vitro model. 2. Serum levels of IGF-I were decreased, but the levels of IGF-II were increased, in diabetic rats compared with controls. The expression of IGFBP-3 in the serum was markedly decreased; in contrast, the expression of IGFBP-1 and -2 was increased in diabetic rats. The expression of IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-4 in the liver of the diabetic group was similar to that in the serum of diabetic rats. 3. In heart tissue of the diabetic group, IGF-I levels were decreased, but IGF-II levels were increased. In addition, the expression of IGFBP-3, IGFBP-1 and IGFBP-2 was decreased in diabetic rats. 4. In the kidney of the diabetic group, IGF-I and IGF-II levels were increased. There was only slight expression of IGFBP-3 in the kidney and this was not altered in diabetic rats. Levels of IGFBP-1 and -2 were markedly increased in the kidney of diabetic rats. 5. Insulin treatment recovered the changes in expression of IGF-I, IGF-II and IGFBPs in the serum, liver, heart and kidney. In the liver, heart and kidney, the expression of the insulin receptor was increased in male diabetic rats. 6. In conclusion, diabetes tissue-specifically alters the IGF system in the liver, heart and kidney in rats; this effect can be recovered by insulin treatment.     

Subacute toxicity evaluation in rats exposed to concrete and hwangto building environments

This study examined the potential adverse effects of the subacute exposure of rats to concrete and hwangto building environments. Polycarbonate was used as a comparison. Groups of 10 male rats were exposed to polycarbonate, concrete, or hwangto cages for a 4-week period in summer or winter. During the study period, the clinical signs, mortality, skin temperature, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. The concentration of total volatile organic compounds (VOCs), temperature, and relative humidity in the each cages were also measured. There were no exposure-related effects in any group of the study examined in the summer. The temperature, relative humidity, and the concentration of VOCs in the cages were similar in all groups. However, in the winter study, significant differences in several parameters were detected among the groups. In the concrete group, there was an increase in the clinical signs, a reduction in the body weight gain, food intake, and liver weight, an increase in the lung weight, and an increase in the histopathological alterations in the lung and thymus. Infrared thermal analysis showed that the skin temperature of the rats in the concrete group was lower than that in the polycarbonate group. However, in the hwangto group, there was a decrease in the clinical signs and an increase in the body weight, food intake, and the weights of the heart, lung, spleen, and epididymides. Overall, the 4-week exposure of the rats to the concrete building environment had adverse effects on the clinical signs, skin temperature, body weight, and some organs in the winter but not in the summer. On the other hand, the exposure of hwangto building environment did not have any exposure-related adverse effects on the general health parameters and skin temperature in rats.     

中青年血清胆红素轻度增高者胆红素与血糖、血脂及血压的关系

目的观察中青年血清胆红素轻度增高者血糖、血脂及血压水平。方法中青年男女556人,高胆红素组296人,对照组260人。测定两组研究对象血清总胆红素、直接胆红素、空腹血糖、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇及血压并对数据进行分析。结果男性胆红素高于女性,差异有统计学意义（P〈0．01）。高胆红素组空腹血糖低于对照组,男性二组差异有统计学意义（P〈0．01）,女性二组差异无统计学意义（P〉0．05）。高胆红素组收缩压低于对照组,但差异无统计学意义（P〉0．05）,舒张压高于对照组,且差异有统计学意义（P〈0．05）。高胆红素组男性总胆固醇、甘油三酯高于对照组,高及低密度脂蛋白胆固醇低于对照组,其中高密度脂蛋白胆固醇与对照组差异有统计学意义（P〈0．05）。高胆红素组女性总胆固醇、甘油三酯、高与低密度脂蛋白胆固醇均高于对照组,但差异无统计学意义（P〉0．05）。空腹血糖与男性总胆红素、直及间接胆红素和女性直接胆红素负相关。舒张压与男性总胆红素及直接胆红素和女性总胆红素及间接胆红素正相关;收缩压与男性胆红素不相关,与女性直接胆红素负相关。男性低密度脂蛋白胆固醇、女性总胆固醇、腰围与直接胆红素负相关。男性腰围与总胆红素、间接胆红素正相关。结论胆红素不同形式对空腹血糖均有影响,中青年阶段空腹血糖随着胆红素的增高而降低。胆红素对中青年男女舒张压的维持有一定作用,对收缩压的影响有性别差异,女性胆红素较高者,舒张压较低。中青年男女在高胆红素水平时有较少的心脑血管危险因素。     

Fumonisin B1 Accumulates in Chicken Tissues over Time and This Accumulation Was Reduced by Feeding Algo-Clay

The toxicokinetics of the food and feed contaminant Fumonisin B (FB) are characterized by low oral absorption and rapid plasma elimination. For these reasons, FB is not considered to accumulate in animals. However, recent studies in chicken and turkey showed that, in these species, the hepatic half-elimination time of fumonisin B1 (FB1) was several days, suggesting that FB1 may accumulate in the body. For the present study, 21-day-old chickens received a non-toxic dose of around 20 mg FB1 + FB2/kg of feed to investigate whether FB can accumulate in the body over time. Measurements taken after four and nine days of exposure revealed increased concentrations of sphinganine (Sa) and sphingosine (So) over time in the liver, but no sign of toxicity and no effect on performances were observed at this level of FB in feed. Measurements of FB in tissues showed that FB1 accumulated in chicken livers from four to nine days, with concentrations of 20.3 and 32.1 ng FB1/g observed, respectively, at these two exposure periods. Fumonisin B2 (FB2) also accumulated in the liver, from 0.79 ng/g at four days to 1.38 ng/g at nine days. Although the concentrations of FB found in the muscles was very low, an accumulation of FB1 over time was observed in this tissue, with concentrations of 0.036 and 0.072 ng FB1/g being measured after four and nine days of exposure, respectively. Feeding algo-clay to the chickens reduced the accumulation of FB1 in the liver and muscle by , approximately 40 and 50% on day nine, respectively. By contrast, only a weak non-significant effect was observed on day four. The decrease in the concentration of FB observed in tissues of chickens fed FB plus algo-clay on day nine was accompanied by a decrease in Sa and So contents in the liver compared to the levels of Sa and So measured in chickens fed FB alone. FB1 in the liver and Sa or So contents were correlated in liver tissue, confirming that both FB1 and Sa are suitable biomarkers of FB exposure in chickens. Further studies are necessary to determine whether FB can accumulate at higher levels in chicken tissues with an increase in the time of exposure and in the age of the animals.     

Hepatic effects of 2-butoxyethanol in rodents.

Chronic inhalation of 2-butoxyethanol resulted in an increase in liver hemangiosarcomas and hepatic carcinomas in male mouse liver. No increase in liver neoplasia was observed in similarly exposed male and female rats or female mice. We proposed that the production of liver neoplasia in the male mouse is the result of oxidative damage secondary to the hemolytic deposition of iron in the liver. This occurs selectively in the male mouse and leads either directly or indirectly to liver neoplasia. To address this proposal, male B6C3F1 mice and male F344 rats were treated with 2-butoxyethanol (via daily gavage; five times per week) at doses of 0, 225, 450, and 900 mg/kg/day (mice) and 0, 225, and 450 mg/kg/day (rats) respectively. Following treatment for 7, 14, 28, and 90 days, DNA synthesis, oxidative damage, hematocrit, and iron deposition were measured in the livers. An increase in hemolysis (measured by a decrease in hematocrit and increase in relative spleen weight) was observed in 2-butoxyethanol-treated rats and mice in a dose-dependent manner. An increase in the percentage of iron-stained Kupffer cells was observed following treatment with 450 and 900 mg/kg of 2-butoxyethanol in mice and 225 and 450 mg/kg of 2-butoxyethanol in rats. A biphasic increase in oxidative damage (8-hydroxydeoxyguanosine and malondialdehyde) was seen in mouse liver after 7 and 90 days of treatment with 2-butoxyethanol, whereas no increases were observed in treated rat liver. Vitamin E levels were reduced by 2-butoxyethanol treatment in both mice and rat liver; however, the basal level of vitamin E was approximately 2.5-fold higher in rat than in mouse liver. A similar biphasic induction of DNA synthesis was seen following 2-butoxyethanol treatment in the mouse. In the mouse liver, increased DNA synthesis was observed in hepatocytes at 90 days and in endothelial cells at 7 and 14 days at all doses. No change in DNA synthesis was seen in 2-butoxyethanol-treated rat liver. No apparent differences in apoptosis and mitosis in the liver were observed in mouse and rat liver between 2-butoxyethanol treatment groups and untreated controls. These results suggest that DNA synthesis, possibly from oxidative stress or Kupffer cell activation, occurs selectively in the mouse liver, primarily in endothelial cells (a target of 2-butoxyethanol neoplasia), following exposure to 2-butoxyethanol.     

Increase in histidine decarboxylase activity in tissues of mice bearing Colon-26 tumor cells

The changes in histidine decarboxylase (HDC) activity, histamine and tele-methylhistamine contents were examined in tissues of mice after the inoculation of Colon-26 tumor cells subcutaneously into the lower back. The HDC activity in the spleen of mice increased significantly 14 days after the inoculation of Colon-26 and the increase in HDC activity continued for up to 28 days. However, the histamine content in the spleen of tumor-bearing mice was not changed significantly during the observation period. In the following experiments, two subclones of the Colon-26 cell line, cachexia-inducing clone-20 and non cachexia-inducing clone-5, were used and the induction of HDC activity in mice was examined in four tissues, spleen, lung, liver and kidney. Both clone-20 and clone-5 induced the increase in HDC activity to the same extent in the spleen and lung, but not in the liver and kidney. As observed using the Colon-26 original cell line, the histamine contents in the four tissues of tumor-bearing mice were not different from those in the control mice. In contrast, the levels of tele-methylhistamine, one of the major catabolites of histamine, in the tumor-bearing mice increased significantly compared with the control mice in all four tissues examined. There was a correlation between the increase in tele-methylhistamine level and the increase in HDC activity in the tissues. A histological study indicated that the tissue mast cells were not increased in spleen and lung of tumor-bearing mice. These findings indicated that the increase in HDC activity in the spleen and lung occurred in parallel with the growth of inoculated tumor cells in mice and suggested that the cells other than mast cells may be involved in the increase in HDC activity. The tumor-bearing state produced histamine with a high turnover rate in the mouse tissues, especially in the spleen and lung. Received: 30 November 1998 / Accepted: 14 April 1999 / Published online: 2 July 1999     

小儿清热片联合康复新液治疗儿童口腔溃疡的临床研究

目的探讨小儿清热片联合康复新液治疗儿童口腔溃疡的临床效果。方法选取2016年1月-2019年1月北京儿童医院收治的86例口腔溃疡患儿,随机分成对照组(43例)和治疗组(43例)。对照组餐后含漱康复新液5min后吐出,10 mL/次,3次/d。治疗组在在对照组基础上口服小儿清热片,2片/次,2次/d。两组均连续治疗5 d。观察两组患儿临床疗效,同时比较治疗前后两组患儿主要症状积分、退热时间、食欲改善时间,外周血白细胞计数(WBC)、中性粒细胞绝对值(NEUT#)水平,以及唾液中肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、表皮生长因子(EGF)水平。结果治疗后,对照组和治疗组临床有效率分别为86.0%、100.0%,两组比较差异有统计学意义(P<0.05)。治疗后,两组患儿溃疡面积、充血程度、疼痛积分均显著低于治疗前(P<0.05),且治疗组下降更显著(P<0.05)。治疗后,治疗组完全退热时间、食欲改善时间较对照组均显著缩短(P<0.05)。治疗后,两组患儿外周血WBC、NEUT#水平较治疗前均显著降低(P<0.05),且治疗组以上血象指标的改善效果比对照组更显著(P<0.05)。治疗后,两组患儿唾液中TNF-α、IL-6、EGF水平均显著下降(P<0.05),且治疗组上述唾液指标水平均显著低于对照组(P<0.05)。结论小儿清热片联合康复新液治疗儿童口腔溃疡的疗效确切,能有效缓解患儿症状,迅速退热,改善食欲,加速溃疡愈合,减少复发,且安全性好。     

柠檬醛的利胆溶石和镇痛抗炎作用的实验研究

目的：研究柠檬醛治疗胆石症、胆囊炎、胆管炎的新适应证。方法：行大鼠胆管插管手术,引流胆汁,测量胆汁流量和胆汁成分;用致石饲料致小鼠胆石形成模型,评价柠檬醛抑制胆石形成的作用;用人胆石体外试验柠檬醛的溶石作用;用常规的疼痛模型和炎症模型,观察柠檬醛的镇痛抗炎作用。结果：柠檬醛有促进胆汁分泌的作用,反复给予柠檬醛仍有显著和持续促进大鼠胆汁分泌的作用,在利胆的同时降低胆汁中的总胆固醇、胆红素、黏液的含量;将柠檬醛予小鼠灌胃给药可抑制其胆囊结石的形成,体外实验可溶解人混合型胆石,并具有镇痛抗炎的作用。结论：柠檬醛具有强而持久的促进低含量胆固醇、胆红素和黏蛋白胆汁的分泌,以及抑制胆石的形成和溶解胆石的作用,因此柠檬醛可望成为治疗胆囊炎、胆管炎、胆石症的新药,而其镇痛抗炎、广谱抗菌的作用有助于消除胆道炎症和症状。     

湘西少数民族地区HCV、HIV及梅毒感染情况调查分析

目的了解湘西少数民族地区丙型肝炎（HCV）、爱滋病（HIV）及梅毒感染情况。方法对术前、产前、输血前及一些特殊检查治疗前进行丙型肝炎病毒抗体（抗-HCV）、人类免疫缺陷病毒抗体（抗-HIV）、梅毒试验（TP-ELISA）的检测分析。结果本地区HCV感染率为0.82%、HIV感染率为0.17%,梅毒感染率为4.28%。结论加强HCV、HIV及梅毒的检测。对明确疾病诊断,指导临床治疗,加强医务人员防护及院内感染工作,避免不必要的医疗纠纷,具有重要的临床和社会意义。     

维生素E联合川芎嗪对缺血再灌注幼鼠视网膜损伤后的保护作用研究

目的 观察维生素E联合川芎嗪对幼鼠视网膜缺血再灌注及其外周血氧化相关物质的影响,探讨其对损伤后保护的作用机制.方法 选取清洁级3周龄幼鼠100只,随机分为5组,每组20只.A组为假造模组、B组为模型组、C组为维生素E干预组、D组为川芎嗪干预组、E组为维生素E联合川芎嗪干预组,再灌注损伤后4h处死幼鼠,检测外周血清谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)、超氧化物歧化酶(superioxide dismutase,SOD)、活性氧类物质(reactive oxygen species,ROS)、丙二醛(malondialdehyde,MDA),用Tunel染色法检测视网膜细胞凋亡情况.结果 幼鼠眼球视网膜细胞Tunel指数B组高于其他4组,E组低于C、D组,D组低于C组(P<0.05).Tunel染色阳性集中在细胞核部位,表现为细胞核固缩.GSH-PX、SOD活性B、C、D、E组均低于A组,C、D、E组高于B组,D、E组高于C组,E组高于D组(P<0.05);B、C、D、E组ROS活性和MDA含量均高于A组,C、D、E组均低于B组,且D、E组低于C组,E组低于D组(P<0.05).结论 维生素E联合川芎嗪能通过抑制凋亡与抗氧化对缺血再灌注视网膜起到很好的保护作用,两药联合应用效果更佳.