尿毒症患者胃肠运动功能障碍

为探讨尿毒症患者胃肠运动功能障碍的特点 ,应用胃肠测压技术对 2 6名尿毒症患者 ,5 1名糖尿病患者 ,16名健康自愿者进行了消化间期移行性复合运动 (MMC)检测 ,连续测定 2 4 0min ;应用放射免疫法检测了上述人员的空腹血浆胃动素水平 ;有 8名尿毒症患者进行了电子胃镜检查。结果表明 :①尿毒症患者MMCⅠ期、Ⅱ期出现的比例明显高于对照组的 13 3% ,总计达 73 1% (P <0 0 1) ,尿毒症组有MMCⅢ期者仅 19 2 % ,明显低于正常对照组(78 0 % ,P <0 0 1)。②在有MMCⅢ期者中 ,尿毒症组胃窦和十二指肠的收缩频率明显低于正常对照组和糖尿病组 (均P <0 0 5 ) ,但胃窦和十二指肠MMCⅢ期的收缩幅度则正常或较高。③尿毒症组空腹血浆胃动素水平明显高于正常对照组和糖尿病组 (均P <0 0 0 1) ,④ 8名行胃镜检查的尿毒症患者中 ,6人为慢性浅表性胃炎 ,2人为贫血性胃改变。提示 :尿毒症患者存在胃肠运动功能障碍 ,主要表现为MMC的异常和高胃动素血症     

Pharmacological and biological evaluation of a series of substituted 1,4-naphthoquinone bioreductive drugs

The indolequinone compound EO9 has good pharmacodynamic properties in terms of bioreductive activation and selectivity for either NAD(P)H:quinone oxidoreductase-1 (NQO1)-rich aerobic or NQO1-deficient hypoxic cells. However, its pharmacokinetic properties are poor and this fact is believed to be a major reason for EO9's lack of clinical efficacy. The purpose of this study was to develop quinone-based bioreductive drugs that retained EO9's good properties, in terms of bioreductive activation, but have improved pharmacokinetic properties. Out of 11 naphthoquinone compounds evaluated, 2-aziridinyl-5-hydroxy-1,4-naphthoquinone (compound 2), 2,3-bis(aziridinyl)-5-hydroxy-1,4-naphthoquinone (compound 3), and 2-aziridinyl-6-hydroxymethyl-1,4-naphthoquinone (compound 11) were selected for further evaluation based on good substrate specificity for NQO1 and selectivity towards NQO1-rich cells in vitro. Compound 3 was of particular interest as it also demonstrated selectivity for NQO1-rich cells under hypoxic conditions. Compound 3 was not metabolised by murine whole blood in vitro (in contrast to compounds 2, 11 and EO9) and pharmacokinetic studies in non-tumour-bearing mice in vivo (at the maximum soluble dose of 60 mg kg(-1) administered intraperitoneally) demonstrated significant improvements in plasma half-life (16.2 min) and AUC values (22.5 microM h) compared to EO9 (T(1/2) = 1.8 min, AUC = 0.184 microM h). Compound 3 also demonstrated significant anti-tumour activity against H460 and HCT-116 human tumour xenografts in vivo, whereas EO9 was inactive against these tumours. In conclusion, compound 3 is a promising lead compound that may target both aerobic and hypoxic fractions of NQO1-rich tumours and further studies to elucidate its mechanism of action and improve solubility are warranted.     

丝裂霉素膀胱内灌注治疗膀胱癌电切术后的疗效观察

目的探讨经尿道电切术及术后使用丝裂霉素膀胱内灌注治疗浅表性膀胱肿瘤的临床疗效。方法对62例膀胱癌患者行经尿道膀胱肿瘤电切术,术后定期应用丝裂霉素膀胱内灌注化疗,并经7～72个月随访,观察膀胱肿瘤复发情况。结果 62例患者无肿瘤复发54例（87%）,复发8例,均再行经尿道膀胱肿瘤电切术（TURBT）并继续丝裂霉素膀胱内灌注,未见全身药物不良反应,仅有3例膀胱灌注药物后出现短期轻度膀胱刺激症状。结论经尿道电切术治疗浅表性膀胱肿瘤具有手术简单、损伤小、出血少、恢复快、疗效好等优点。丝裂霉素膀胱内灌注能明显减少浅表性膀胱肿瘤的复发。     

丝裂霉素C在青光眼滤过术中应用的远期疗效观察

目的了解丝裂霉素C（mitomyeinMMC）在青光眼滤过术后抗瘢痕形成的临床效果。方法回顾性分析182例195眼常规小梁切除联合应用丝裂霉素C青光眼患者并术后随访6—24个月,平均13个月。结果在195眼中168眼疗效好,眼压控制在（13．7±2．1）mmHg、11眼疗效较好,不用或仅用局部抗青光眼药物眼压≤21mmHg、16眼出现并发症效果差。手术成功率91．8％。功能性滤过泡为86％。手术后角膜上皮损害6眼,低眼压、浅前房发生9眼。结论MMC能抑制青光眼滤过术后瘢痕形成,大大提高了青光眼滤过术的成功率,远期效果好,但使用时应掌握适应证,预防并发症的发生。     

The potential clinical value of GML and the p53 gene as a predictor of chemosensitivity for colorectal cancer

Background. Adjuvant chemotherapy with 5-fluorouracil (5-FU) and mitomycin C (MMC) has commonly been used after resection of colorectal cancer. The aim of this study was to determine the predictive value of p53 mutation or the expression of GML, a target of p53, for sensitivity to 5-FU and MMC. Methods. We analyzed p53 mutations and the expression of GML in six colorectal cancer cell lines (SW837, DLD-1, RPMI4788, WiDr, HT-29, and HCT116), and examined the correlation between genetic changes and in-vitro chemosensitivity to MMC and 5-FU by measuring the colony-forming ability in these cell lines. We also introduced GML cDNA into a cell line that lacked endogenous GML expression to investigate changes in sensitivity to MMC and 5-FU. Results. The sensitivity to MMC was highest in HCT116, which had no p53 gene abnormalities and expressed endogenous GML, and lowest in RPMI4788 cells, which had neither p53 gene abnormalities nor expression of endogenous GML. For 5-FU treatment with 24-h exposure, HCT116 showed the highest sensitivity, and SW837, which had p53 mutations without expression of GML, showed the lowest sensitivity. The introduction of GML cDNA to RPMI4788 (RPMI4788-GML) showed that the sensitivity of RPMI4788-GML to MMC was enhanced almost to the level of HCT116 cells. However, when RPMI4788-GML were exposed to 5-FU for 24 h, the sensitivity of RPMI4788-GML was slightly increased compared with that of the parental cells, but was slightly lower than that of HCT116. Conclusion. GML expression and p53 mutation in colorectal cancer may be useful predictive genetic markers for sensitivity to MMC and 5-FU, respectively. Received: June 30, 2000 / Accepted: December 8, 2000     

Safety evaluation of steroidal saponin DT-13 isolated from the tuber of Liriope muscari (Decne.) Baily

Steroidal saponin DT-13 (25 (R, S)-ruscogenin-1-O-[β-d-glucopyranosyl - (1 → 2)] [β-d-xylopyranosyl-(1 → 3)]-β-d-fucopyranoside) is the main active component of the tube of Liriope muscari (Decne.) Baily and has been studied as a candidate drug for cancer metastasis. The objective of this study was to evaluate the safety of DT-13 systematically by genotoxicity and acute oral toxicity and subchronic 90-day oral gavage toxicity. Results of Ames test confirmed that DT-13 did not induce mutations in histidine auxotrophs Salmonella typhimurium (TA 97, TA 98, TA 100 and TA 102) both in the presence and absence of metabolic activation system at the doses of 0.05-500 μg/plate. Meanwhile, DT-13 did not induce clastogenicity at doses of 1250, 2500 and 5000 mg/kg in mouse micronucleus test. And the single oral dose of DT-13 at 5000 mg/kg did not produce mortality or significant changes in the general behavior and gross appearance of the internal organs of mice. In subchronic toxicity study, DT-13 was administrated to Sprague-Dawley rats via oral gavage at doses of 10, 60 and 360 mg/kg for 90 days. Necropsy, hematological and biochemical analysis, and histopathological examination did not reveal any remarkable and treatment related changes. In conclusion, DT-13 is of low toxicity at the tested doses.     

活性碳吸附丝裂霉素C腹腔化疗的临床实验研究

目的：通过动物实验及临床应用,证实活性碳吸附丝裂霉素C腹腔化疗能治疗和预防进展期胃癌术后腹腔复发,从而提高患者的生存率。方法：利用人胃癌裸鼠模型进行活性碳（CH）吸附MMC腹腔化疗的动物实验,共分4组,每组8只荷瘤裸鼠。实验组腹腔给予CH－MMC,腹腔化疗组腹腔给予MMC,静脉化疗组经内眦静脉给予MMC,对照组腹腔注入等容量生理盐水。临床应用时将可以根治手术的64例进展期T3~4NxM0）胃癌病例随机分为2组,实验组于手术结束时腹腔内给予经医用活性碳吸附的MMC 50mg,术后3个月开始常规静脉化疗。对照组仅于手术后3周开始静脉化疗。结果：动物试验结果表明实验组疗效最佳,仅于2只小鼠腹腔发现较小（1~3mm）的转移灶;单纯腹腔化疗组中,有3只小鼠腹腔出现较广泛的转移灶,直径在3~15mm之间;静脉化疗组中6只小鼠腹腔出现广泛转移病灶;对照组8只小鼠腹腔均发生广泛转移瘤。经过平均15．4个月2~36个月的随访,临床应用实验组较对照组2、3年生存率分别提高42．03％及53．44％（76．27％76．27％和34．24％22．83％,P＜ 0．05。结论：活性碳吸附MMC腹腔化疗确能提高进展期胃癌根治性手术后无瘤生存率。     

姜黄素与MMC联用对胃癌MGC-803细胞存活率和凋亡率的影响

目的:探索姜黄素与低剂量或中剂量化疗药丝裂霉素C(MMC)联用对胃癌MGC-803细胞存活率和凋亡率的影响,为临床上应用姜黄素作为胃癌化疗药MMC的增效剂,以减少MMC使用剂量、降低其毒副作用提供实验依据.方法:将姜黄素和MMC作用于体外培养的胃癌MGC-803细胞24 h,采用MTT方法检测药物作用对MGC-803细胞存活率的影响;应用基于FITC-Annexin V/PI双染的流式细胞技术检测药物作用对MGC-803细胞凋亡的影响.结果:姜黄素(25 μmol·L^-1)与低剂量MMC(5.98 μmol·L^-1)联用组的细胞存活率显著低于中剂量MMC(11.96 μmol·L^-1)单用组(P <0.05);姜黄素与中剂量MMC(11.96 μmol·L^-1)联用组的细胞存活率小于高剂量MMC(23.92 μmol·L^-1)单用组,差异具有显著性(P <0.05).而姜黄素与低剂量MMC联用组的细胞凋亡率显著高于中剂量MMC单用组(P <0.05);姜黄素与中剂量MMC联用组的凋亡率显著大于高剂量MMC单用组(P <0.05).结论:姜黄素与与较低剂量MMC联用对胃癌MGC-803细胞的生长抑制作用和凋亡诱导作用显著大于较高剂量MMC单独作用的效果,姜黄素对MMC抗胃癌细胞的作用具有增强效应.     

汞化合物对人体外淋巴细胞的DNA损伤的比较研究

对人体外淋巴细胞用不同浓度的甲基氯化汞（ＭＭＣ）和氯化汞（ＭＣ）处理１ｈ，观察ＤＮＡ损伤的程度，采用细胞琼脂糖凝胶电泳技术（ＳＣＧＥ）进行比较研究。这两种汞化物均不同程度的显示了剂量反应关系。ＤＮＡ损伤的程度从１０－５ｍｏｌ／Ｌ起与空白对照相比，呈现有意义的增加，细胞ＤＮＡ断裂频率的增加与毒性呈现为线性增长的关系。剂量愈高，则ＤＮＡ的彗尾链愈长，两种化合物在同样的实验条件下显示了相似的分裂剂的潜能，氯化汞表现出的遗传毒性更明显     

铁缺乏对鼠肝癌前期病变影响的实验研究

利用大白鼠复制肝癌前病变发生的动物摸型，观察铁缺乏在肝癌发生的第二阶段，既癌前病灶转化为增生结节过程中的作用。结果发现：铁缺乏组中，可能转变为癌的ＧＧＴ染色阳性的持续性结节及ＨＥ染色的肝细胞增生性细节数显著减少。提示铁缺乏在肝癌前病灶转化为增生结节的过程中有抑制作用。