表面具有亲水性聚合物链的聚苯乙烯毫微粒在胃肠道的粘液粘附作用

毫微粒作为多肽药物鲑降钙素（ｓＣＴ）口服给药载体的可能性在大鼠已被研究。已经证实毫微粒能保护ｓＣＴ免遭消化酶的催化降解,并且该稳定作用受大分子单体结构的影响。本文讨论了毫微粒的化学结构对其在胃肠道的粘液粘附作用的影响和强度,以及毫微粒的粘液粘附作用和对ｓＣＴ体内吸收增强作用之间的相关性。聚Ｎ－异丙基丙烯酰胺（ＰＮＩＰＡＡｍ）、聚乙烯胺（ＰＶＡｍ）、聚甲基丙烯酸（ＰＭＡＡ）、聚Ｎ－乙烯基乙酰胺（ＰＮＶＡ）的毫微粒制备采用先前已报道方法,由２,２－偶氮二异丁腈引发大分子单体和苯乙烯之间的分散共聚合反…     

N－［4－［4－（4－甲氧基苯基）－1－哌嗪基］苯基］氨基甲酰肼的合成

Ｎ－［４－［４－（４－甲氧基苯基）－１－哌嗪基］苯基］氨基甲酰肼的合成吴义杰，周廷森，刘超美，陈志胜（第二军医大学药学院，上海２００４３３）ＳＹＮＴＨＥＳＩＳＯＦＮ－［４－［４－（４－ＭＥＴＨＯＸＹＰＨＥＮＹＬ）－１－ＰＩＰＥＲＡＺＩＮＹＬ］ＰＨＥＮ...     

6β—三苯甲基氨基青霉烷酸苄酯的合成

６β┐三苯甲基氨基青霉烷酸苄酯的合成ＳＹＮＴＨＥＳＩＳＯＦＢＥＮＺＹＬ６β┐（ＴＲＩＰＨＥＮＹＬＭＥＴＨＹＬＡＭＩＮＯ）ＰＥＮＩＣＩＬＬＡＮＡＴＥ沈舜义张芸徐屹军（上海医药工业研究院，上海２０００４０）ＳＨＥＮＳｈｕｎ－Ｙｉ，ＺＨＡＮＧＹｕｎ，ＸＵＹ...     

金霉酸族抗肿瘤抗生素SIPI－91－81A的分离，纯化和鉴定

金霉酸族抗肿瘤抗生素ＳＩＰＩ－９１－８１Ａ的分离，纯化和鉴定姜健，龚炳永（上海医药工业研究院，上海２０００４０）ＡＵＲＥＯＬＩＣＡＣＩＤＡＮＴＩＢＩＯＴＩＣＳＳＩＰＩ－９１－８１ＡＩＳＯＬＡＴＯＮ，ＰＵＲＩＦＩＣＡＴＩＯＮＡＮＤＳＴＲＵＣＴＵＲＥＤＥ...     

静脉普鲁卡因复合麻醉患者红细胞NADH细胞色素b5还原酶活力的研究

观察了ＩＰＡ患者红细胞ＮＡＤＨ－Ｃｙｔ ｂ５Ｒ活力与血中Ｍｅｒ Ｈｂ含量的变化及亚甲蓝对Ｍｅｔ Ｈｂ的治疗效果。发现随着ＩＰＡ时间的延长，患者ＮＡＤＨ－ｃｙｔｂ５Ｒ活力呈进行性降低，并与Ｍｅｔ Ｈｂ含量在ＩＰＡ期间始终呈高度密切的负相关关系。ＩＰＡ至１２０分时经亚甲蓝（１ｍｇ／ｋｇ）治疗后，Ｃｙｔｂ５Ｒ活力明显增高接近手术前水平，Ｍｅｔ Ｈｂ含量也显著降低，提示ＩＰＡ患者普遍存在的Ｍｅｔ Ｈｂ血症     

降血脂药苯扎贝特的合成

降血脂药苯扎贝特的合成ＳＹＮＴＨＥＳＩＳＯＦＨＹＰＯＬＩＰＩＤＥＭＩＣＤＲＵＧＢＥＺＡＦＩＢＲＡＴＥ曹志荣＊黄国强△（湖南医药工业研究所，长沙４１００１４）ＣＡＯＺｈｉ－Ｒｏｎｇ＊，ＨＵＡＮＧＧｕｏ－Ｑｉａｎｇ（ＨｕｎａｎＩｎｓｔｉｔｕｔｅｏｆＰｈａ...     

人抑胃肽溶液构象的荧光光谱学研究

运用荧光光谱方法研究了用固相合成法得到的人抑胃肽（ＧＩＰ－４２）及其类似物的内源荧光特性，Ｉ＾－动态荧光淬火以及与ｂｉｓ－ＡＮＳ结合的荧光，结果表明：ＧＩＰ－４２在溶液中具有一定的构象，其Ｔｒｐ残基荧光被Ｉ＾－淬灭的结果表现为双相，淬灭常数分别为１１．５Ｌ／ｍｏｌ和１．２Ｌ／ｍｏｌ，ＧＩＰ－４２肽中有一疏水区能与探针ｂｉｓ－ＡＮＳ结合，在Ｎ－端７个残基除去后所得到的２５肽（ＧＩＰ－２５）分子中，Ｉ     

塞利洛尔的合成

塞利洛尔的合成ＳＹＮＴＨＥＳＩＳＯＦＣＥＬＩＰＲＯＬＯＬ李志军＊李怀生左志杰姜海（河南省医药工业研究所，开封４７５００３）ＬＩＺｈｉ－Ｊｕｎ＊，ＬＩＨｕａｉ－Ｓｈｅｎｇ，ＺＵＯＺｈｉ－Ｊｉｅ，ＪＩＡＮＧＨａｉ（ＨｅｎａｎＩｎｓｔｉｔｕｔｅｏｆＰａｒｍ...     

尼卡地平合成路线图解

尼卡地平合成路线图解杜玉民（河北医学院药学系，石家庄０５００１７）ＧＲＡＰＨＩＣＡＬＳＹＮＴＨＥＴＩＣＲＯＵＴＥＳＯＦＮＩＣＡＲＤＩＰＩＮＥ￥ＤＵＹｕ－Ｍｉｎ（ＤｅｐａｒｔｍｅｎｔｏｆＰｈａｒｍａｃｙ，ＨｅｂｅｉＭｅｄｉｃａｌＣｏｌｌｅｇｅ，Ｓｈｉｊ...     

蒽环类抗生素SIPI－89－4468A的分离、纯化和鉴定

蒽环类抗生素ＳＩＰＩ－８９－４４６８Ａ的分离、纯化和鉴定姜健，范少霞，龚炳永（上海医药工业研究院，上海２０００４０）ＩＳＯＬＡＴＩＯＮ，ＰＵＲＩＦＩＣＡＴＩＯＮＡＮＤＳＴＲＵＣＴＵＲＥＤＥＴＥＲＭＩＮＡＴＩＯＮＯＦＡＮＴＨＲＡＣＹＣＬＩＮＥＡＮＴＩＢ...     

RP-HPLC快速测定马铃薯片中微量丙烯酰胺含量

目的:建立马铃薯片中微量丙烯酰胺的快速检测方法。方法:采用 Luna C_(18)(2)色谱柱(200 mm×4.6 mm,5μm);流动相甲醇-水(5:95),流速1 mL·min~(-1);检测器 SPD-10Avp,检测波长210 nm。结果:峰面积 Y 与进样量 X 在0.0002648～0.002648μg范围内线性关系良好(r=0.9992),检测限为0.0506μg·mL~(-1),平均加样回收率(n=3)为93.0%。精密度试验的 RSD 值为2.8%。重复性试验的 RSD 为1.9%。结论:该方法具有准确、简便、快速的特点,可用于薯片中丙烯酰胺的微量检测。     

Juvenile rats do not exhibit elevated sensitivity to acrylamide toxicity after oral administration for 12 weeks

Acrylamide (AA), a neurotoxic, testicular toxic, genotoxic and carcinogenic chemical, has been reported to be formed in processed food, and sensitivity to AA intoxication in childhood is a concern. In the present study, to clarify the general toxicological profile of AA in juvenile rats, subchronic toxicity was evaluated in F344 rats administered AA in the drinking water at 0 (control), 10, 20 and 40 ppm, presented to the dams (three per group) immediately after the birth of their litters, through lactation (3 weeks), and directly to the offspring in their drinking water after weaning for a further 9 weeks (12 weeks total). Treatment with AA caused a decrease in body weights in 20 and 40 ppm F₁ females, compared with the controls. Average AA intake throughout the treatment period for the 10, 20 and 40 ppm groups after weaning was equivalent to 1.0, 2.1 and 4.4 mg kg^?1 body weight per day, respectively, in males and 1.2, 2.5 and 4.9 mg kg^?1 body weight per day, respectively, in females. No toxicologically significant organ weight changes were observed. AA‐induced histopathological changes were limited to focal degeneration and necrosis of the seminiferous epithelium in the testes and desquamated epithelium in the ducts of epididymides, noted only in 40 ppm males. Taken together with previous reports, juvenile rats are not necessarily more susceptible to AA‐induced toxicity as compared with young adults. Copyright © 2011 John Wiley & Sons, Ltd.     

Camellia sinensis (green tea) extract attenuate acrylamide induced testicular damage in albino rats

Acrylamide is a proved toxin for testicular function, found in food when heated for long period of time. Green tea (Camellia sinensis) is a potent antioxidant; the aim of this study was to investigate the protective effect of green tea extract against the toxic effects of acrylamide in rat testes. Methods: acrylamide was administered orally to rats in different doses and also the extract of green tea was administered orally to different groups of animals in combination with the acrylamide. The weight of animals, testosterone hormone level and histopathological effect upon testicles were evaluated. Results: Testosterone hormone level in serum, and histopathological findings were significantly improved with the co‐administration of green tea extract with the acrylamide. Green tea extract reversed all the toxic effects of acrylamide even in high dose for long period (90 days). Conclusion: Green tea extract is a potent antioxidant antidote for the acrylamide toxic effects upon testicular function. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1155–1161, 2014.     

聚丙稀酰胺水凝胶及单体的细胞染色体实验观察

目的对不同浓度的聚丙稀酰胺水凝胶及单体进行诱变实验,观察聚丙稀酰胺水凝胶及单体对哺乳类动物细胞遗传毒性的影响。方法采用细胞培养染色体畸变技术。结果聚丙稀酰胺水凝胶各剂量组与空白对照组差异无显著,丙烯酰胺单体诱导非整倍体形成。结论聚丙稀酰胺水凝胶没有染色体畸变作用,丙烯酰胺致畸作用有剂量反应关系,高浓度诱发大量非整倍体形成及结构变异,低浓度无诱发CHL(仓鼠肺成纤维细胞)细胞染色体畸变作用。     

关注某些医用产品中丙烯酰胺的潜在风险

根据世界卫生组织发布的有关文件。简要概述了丙烯酰胺以及代谢产物在动物方面的研究和有限的人体研究情况．主要涉及神经毒性、生育毒性、致癌性和遗传毒性及其可能发生的机制等。结果表明：丙烯酰胺引起的神经毒性可能与丙烯酰胺有关；导致动物多器官肿瘤的发生与丙烯酰胺的代谢产物环氧丙酰胺有关。     

Metabolism and hemoglobin adduct formation of acrylamide in humans.

Acrylamide (AM), used in the manufacture of polyacrylamide and grouting agents, is produced during the cooking of foods. Workplace exposure to AM can occur through the dermal and inhalation routes. The objectives of this study were to evaluate the metabolism of AM in humans following oral administration, to compare hemoglobin adduct formation on oral and dermal administration, and to measure hormone levels. The health of the people exposed under controlled conditions was continually monitored. Prior to conducting exposures in humans, a low-dose study was conducted in rats administered 3 mg/kg (1,2,3-13C3) AM by gavage. The study protocol was reviewed and approved by Institute Review Boards both at RTI, which performed the sample analysis, and the clinical research center conducting the study. (1,2,3-13C3) AM was administered in an aqueous solution orally (single dose of 0.5, 1.0, or 3.0 mg/kg) or dermally (three daily doses of 3.0 mg/kg) to sterile male volunteers. Urine samples (3 mg/kg oral dose) were analyzed for AM metabolites using 13C NMR spectroscopy. Approximately 86% of the urinary metabolites were derived from GSH conjugation and excreted as N-acetyl-S-(3-amino-3-oxopropyl)cysteine and its S-oxide. Glycidamide, glyceramide, and low levels of N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)cysteine were detected in urine. On oral administration, a linear dose response was observed for N-(2-carbamoylethyl)valine (AAVal) and N-(2-carbamoyl-2-hydroxyethyl)valine (GAVal) in hemoglobin. Dermal administration resulted in lower levels of AAVal and GAVal. This study indicated that humans metabolize AM via glycidamide to a lesser extent than rodents, and dermal uptake was approximately 6.6% of that observed with oral uptake.     

聚丙烯酰胺水凝胶注射术后并发症原因初探

目的 探讨聚丙烯酰胺水凝胶注射术后并发症发生的原因及治疗方法。方法 回顾分析2000年12月-2005年10月所收治的外院注射聚丙烯酰胺水凝胶后发生并发症的64例患者的病历资料．年龄23-54岁，其中注射聚丙烯酰胺水凝胶隆乳者51例，隆鼻2例，丰颞5例，面部局限性凹陷充填6例。结果 51例注射隆乳术后并发症患者B超检查显示分别在皮下、乳腺内、胸大肌筋膜及胸大肌内有不等量的聚丙烯酰胺水凝胶存在。18例免疫球蛋白有异常改变。5例血清内检测出丙烯酰胺单体。平均0．011mg／ml：胶体取出6个月以上2例患者血清内均未检测到丙烯酰胺单体。取出注射物中有16例丙烯酰胺单体阳性．平均含量0．04mg／g。结论 聚丙烯酰胺水凝胶注射入人体后其并发症有局部并发症和全身并发症2大类，局部并发症多与操作不当有关，而全身并发症则考虑与病人免疫学改变以及可能存在的肢体分解有关．另外也不排除心理因素。     

Acrylamide toxicity in isolated rat hepatocytes

Acrylamide (ACR) is an important industrial chemical used primarily in the production of polymers and co-polymers. Acrylamide is mainly neurotoxic to experimental animals as well as humans and has also been shown to be mutagenic and carcinogenic. The present study was designed to investigate the toxicity of ACR on isolated rat hepatocytes. The hepatocytes were isolated by collagenase perfusion method and were incubated with different concentrations of ACR (0.1, 1, 10 m ) for 2 hours. Cell viability by trypan blue exclusion and leakage of the enzymes such as alanine transaminase (ALT) and aspartate transaminase (AST) were determined. Reduced glutathione (GSH), glutathione S-transferase (GST) activity were also measured. A significant decrease in the cell viability was observed after exposure to 10 m ACR for 30 min, while 1 m ACR caused a significant decrease in the viability after 60 min. ALT leakage was parallel to the cell viability. AST leakage was significantly increased at 30 min of incubation with 10 m ACR, whereas 2 hours of incubation was required for the leakage of AST from rats hepatocytes with 1 m ACR. 10 m ACR decreased significantly GSH as early as 30 min, while GSH level was decreased at 60 min after exposure to 1 m ACR. Also, the GST activity increased with increasing the dose of ACR. Cytochrome P450 concentration was decreased after exposure to 10 m ACR. The effect of ACR on cell viability, ALT and AST leakage, GSH and GST activity was time and dose dependent.     

Kinetics of elimination of urinary metabolites of acrylamide in humans.

Acrylamide (AM), used in the manufacture of polyacrylamide and grouting agents, is produced during the cooking of foods. Workplace exposure to AM can occur through the dermal and inhalation routes. The objective of this study was to define the kinetics of elimination of AM and its metabolites following oral and dermal administration. This is the second part of a study in which metabolites and hemoglobin adducts of AM were determined in people (Fennell et al., 2005, Toxicol. Sci. 85, 447-459). (1,2,3-(13)C(3))AM was administered in an aqueous solution orally (single dose of 0.5, 1.0, or 3.0 mg/kg) or dermally (three daily doses of 3.0 mg/kg) to sterile male volunteers. Urine samples were collected at 0-2, 2-4, 4-8, 8-16, and 16-24 h following administration orally, or at 0-2, 2-4, 4-8, 8-16, and 16-24 h following each of three daily dermal doses. (13)C(3)-AM and its metabolites in urine, (13)C(3)-glycidamide, (13)C(3)-N-acetyl-S-(3-amino-3-oxopropyl)cysteine and its S-oxide, and (13)C(3)-N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)cysteine, were quantitated using liquid chromatography-tandem mass spectrometry. The recovered urinary metabolites accounted for 45.6, 49.9, and 39.9% of a 0.5, 1.0, and 3.0 mg/kg oral dose (0-24 h), respectively, and for 4.5% of the dose after 3 mg/kg was administered daily for 3 days dermally (0-4 days). These results indicate that after oral administration AM is rapidly absorbed and eliminated. The half-life estimated for elimination of AM in urine was 3.1-3.5 h. After dermal administration, AM uptake is slow. This study indicated that skin provides a barrier that slows the absorption of AM, and results in limited systemic availability following dermal exposure to AM.