Immunohistochemically demonstrated variation in expression of cathepsin E between uracil-induced papillomatosis and N-butyl-N-(4-hydroxybutyl)nitrosamine-induced preneoplastic and neoplastic changes in rat urinary bladder

Expression of rat urinary bladder cathepsin E in benign papillomatosis induced by uracil and various stages of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced carcinogenesis was investigated immunohistochemically. Seven-week-old, male F344/DuCrj rats were used. In the normal urothelium of control rats, cathepsin E stained in all layers of cells, although in umbrella cells and some basal cells the reaction was relatively weak. In rats given a diet containing 3% uracil for 5 weeks immunoreactivity of cathepsin E in uracil-induced papillomatosis was consistently homogeneous in all layers, but weaker than in normal urothelium. In rats given 0.05% BBN in drinking water for 12 weeks and subsequently maintained without treatment for 48 weeks cells with little cathepsin E, never observed in normal urothelium, appeared at 5 weeks above the basement membrane in the earliest stage of BBN-induced urinary bladder cancer (simple hyperplasia). Throughout the neoplastic process, groups of cells with a little cathepsin E were randomly distributed, with expression in the urothelium being markedly unstable. Almost all areas of squamous cell proliferation in TCC were negative for cathepsin E. Instability of cathepsin E expression in rat urothelium therefore appears characteristic for carcinogenesis and offers the possibility of using this feature as an early biomarker for urinary bladder carcinogenesis.     

同位素稀释-气相色谱串联质谱法测定啤酒中4种亚硝胺类化合物

目的 建立啤酒中4种N-亚硝胺类化合物（N-亚硝基二甲胺、N-亚硝基二乙胺、N-亚硝基二丙胺、N-亚硝基二苯胺）的同位素稀释固相萃取-气相色谱串联质谱测定方法。 方法 样品经活性炭固相萃取小柱富集、二氯甲烷洗脱,洗脱液经氮吹浓缩定容后,采用INNOWAX毛细管色谱柱分离,多反应监测（MRM）模式检测,同位素稀释内标法定量。 结果 各物质在5 μg/L~200 μg/L范围内线性关系良好,相关系数均大于0.9995。方法的检出限为0.03-0.10 μg/L,定量限为0.10~0.33 μg/L。不同水平的加标回收率为72.1%~100.3%,相对标准偏差为1.5%~9.5%（n=6）。 结论 该方法操作简单,灵敏度和准确度高,适用于啤酒中4种N-亚硝胺类化合物的测定。     

胃及十二指肠食管反流对致癌剂诱发大鼠食管肿瘤的影响

目的：通过动物实验研究胃液及十二指肠内容物反流对食管肿瘤发生过程的影响。方法：通过不同手术方式制作３种动物模型：胃食管反流（Ｇ）组,单纯十二指肠食管反流（Ｄ）组,十二指肠,胃混合食管反流（ＤＧ组）及无反流对照组（Ｃ组）。术后均注射食管致癌剂甲基戊基亚硝胺（ＭＡＮＡ）,于２６周取出食管进行大体及光镜下形态学观察。结果：各反流组出现严重食管粘膜损害,病变较对照组明显加重且发生率高,病变严重程度Ｄ组〉Ｄ     

橘核及其炮制品清除亚硝酸盐及阻断亚硝胺合成的研究

目的研究橘核及盐橘核对亚硝酸盐的清除能力及对亚硝胺合成的阻断能力。方法在模拟人体胃液(pH=3.0,温度为37℃)条件下,采用分光光度法测定橘核及盐橘核对亚硝酸盐的清除率和对亚硝胺合成的阻断率。结果橘核、盐橘核提取液对亚硝酸钠的最大清除率分别为48.09%、49.19%;橘核提取液对亚硝胺合成无阻断作用,盐橘核提取液对亚硝胺合成的最大阻断率为21.32%;结论通过与Vc的对照分析可知,橘核及盐橘核提取液清除亚硝酸盐的作用都较强,炮制后对亚硝酸盐的清除率有所增加,橘核本身对亚硝胺无阻断作用,炮制后对亚硝胺产生一定的阻断作用。     

Chemoprevention of liver cancer by plant polyphenols

Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most frequent tumors representing the fifth commonest malignancy worldwide and the third cause of mortality from cancer. Currently, the treatments for HCC are not so effective and new strategies are needed for its fight. Chemoprevention, the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenesis is considered an important way for confronting HCC. Many of the chemopreventive agents are phytochemicals, namely non-nutritive plant chemicals with protective or disease preventive properties. In this review, we focus on plant polyphenols, one of the most important classes of phytochemicals, their chemopreventive properties against HCC and discuss the molecular mechanisms accounting for this activity.     

A p53 mutation in exon 5 associated with adenovirus transformation

The adenovirus type 5 (Ad5) 55-kDa E1B oncoprotein has been shown to form complexes with the p53 tumor suppressor protein. These complexes are thought to interfere with normal p53 activity and may be responsible for the paucity of p53 mutations in cells transformed by these viruses. This report describes an example of a p53 mutation in exon 5 in an Ad5-transformed cell line that exhibited less expression of E1B 55-kDa protein and a longer tumor-latency phenotype than another Ad5-transformed cell line expressing wild-type p53. The finding of a p53 mutation in an Ad5-transformed cell line is unusual, especially considering the current theory that p53-E1B interactions play an important role in adenovirus transformation. This mutation could represent an alternative method of inactivating p53 function in the absence of sufficient levels of E1B 55-kDa oncoprotein. © 1995 Wiley-Liss Inc.     

鼻咽癌患者和正常人尿液中的亚硝胺水平

作者采用气相色谱－热能分析法，测定了７０份鼻咽癌患者和正常人尿样中的挥发性亚硝胺水平。两组尿样中的二甲基亚硝胺水平分别为０．５５±０．４０μｇ／Ｌ、０．４５±０．３４μｇ／Ｌ，两者比较无显著性差异（Ｐ＞０．０５）；二乙基亚硝胺水平分别为０．２２±０．２０μｇ／Ｌ、０．３２±０．２６μｇ／Ｌ，两者比较亦无显著性差异（Ｐ＞０．０５）。然而，鼻咽癌患者尿样中的亚硝胺阳性检出率高达６２．９％，正常人为５４．３％，提示鼻咽癌的发生与当地居民的饮食因素和内源性亚硝胺形成有关。     

Effects of polyunsaturated fatty acids on voltage-gated K+ and Na+ channels in rat olfactory receptor neurons

Although the polyunsaturated fatty acids arachidonic acid (AA) and docosahexaenoic acid (DHA) are enriched in the olfactory mucosa, their possible contribution to olfactory transduction has not been investigated. This study characterized their effects on voltage‐gated K⁺ and Na⁺ channels of rat olfactory receptor neurons. Physiological (3–10 µm ) concentrations of AA and DHA potently and irreversibly inhibited the voltage‐gated K⁺ current in a voltage‐independent manner. In addition, both compounds significantly reduced the inhibitory potency of the odorants acetophenone and amyl acetate at these channels. By comparison, the steady‐state effects of both AA and DHA on the voltage‐gated Na⁺ channel were relatively weak, with half‐maximal inhibition requiring ≈ 35 µm of either compound. However, a surprising finding was that the initial application of 3 µm AA to a naïve neuron caused a strong but transient inhibition of the Na⁺ current. The channels became almost completely resistant to this inhibition within 1 min, and a 2‐min wash in control solution was insufficient to restore the strong inhibitory effect. These observations suggest that polyunsaturated fatty acids have the potential to strongly influence the coding of odorant information by olfactory receptor neurons.     

A short history of nitroglycerine and nitric oxide in pharmacology and physiology

1. Nitroglycerine (NG) was discovered in 1847 by Ascanio Sobrero in Turin, following work with Theophile-Jules Pelouze. Sobrero first noted the 'violent headache' produced by minute quantities of NG on the tongue. 2. Constantin Hering, in 1849, tested NG in healthy volunteers, observing that headache was caused with 'such precision'. Hering pursued NG ('glonoine') as a homeopathic remedy for headache, believing that its use fell within the doctrine of 'like cures like'. 3. Alfred Nobel joined Pelouze in 1851 and recognized the potential of NG. He began manufacturing NG in Sweden, overcoming handling problems with his patent detonator. Nobel suffered acutely from angina and was later to refuse NG as a treatment. 4. During the mid-19th century, scientists in Britain took an interest in the newly discovered amyl nitrite, recognized as a powerful vasodilator. Lauder Brunton, the father of modern pharmacology, used the compound to relieve angina in 1867, noting the pharmacological resistance to repeated doses. 5. William Murrell first used NG for angina in 1876, although NG entered the British Pharmacopoeia as a remedy for hypertension. William Martindale, the pharmaceutical chemist, prepared '...a more stable and portable preparation': 1/100th of a grain in chocolate. 6. In the early 20th century, scientists worked on in vitro actions of nitrate-containing compounds although little progress was made towards understanding the cellular mode of action. 7. The NG industry flourished from 1900, exposing workers to high levels of organic nitrites; the phenomena of nitrate tolerance was recognized by the onset of 'Monday disease' and of nitrate-withdrawal/overcompensation by 'Sunday Heart Attacks'. 8. Ferid Murad discovered the release of nitric oxide (NO) from NG and its action on vascular smooth muscle (in 1977). Robert Furchgott and John Zawadski recognized the importance of the endothelium in acetylcholine-induced vasorelaxation (in 1980) and Louis Ignarro and Salvador Moncada identified endothelial-derived relaxing factor (EDRF) as NO (in 1987). 9. Glycerol trinitrate remains the treatment of choice for relieving angina; other organic esters and inorganic nitrates are also used, but the rapid action of NG and its established efficacy make it the mainstay of angina pectoris relief.