Biological characteristics of lactosaminated N-succinyl-chitosan as a liver-specific drug carrier in mice

Lactosaminated N-succinyl-chitosan (Lac-Suc) was prepared by reductive amination of N-succinyl-chitosan (Suc) and lactose using sodium cyanoborohydride. Six-day reaction using lactose (12.8-fold (w/w)) yielded Lac-Suc with lactosamination degree of 30% (mol/sugar unit). Fluorescein thiocarbamyl-Lac-Suc (Lac-Suc-FTC) was prepared by labeling Lac-Suc with fluorescein isothiocyanate. Lac-Suc-FTC was injected intravenously at a dose of either 1 (high dose) or 0.2 (low dose) mg/mouse. At both doses, Lac-Suc-FTC initially underwent fast hepatic clearance, showed maximum liver localization at 8 h, and the amounts localized there were maintained even at 48 h post-injection. Very slow excretion into feces and urine was observed. The ratio of liver AUC_{0–48 h} to plasma AUC_{0–48 h} at low dose was three times higher than that at high dose. On the other hand, the Suc derivative, Gal-Suc, obtained by reductive amination of Suc/galactose showed very little distribution to the liver similarly to Suc itself. Further, since the liver uptake of Lac-Suc-FTC was inhibited by asialofetuin, it was suggested that the liver distribution of Lac-Suc should be concerned with asialoglycoprotein receptor. Thus, Lac-Suc was found available as a carrier exhibiting a high affinity to and long retention in the liver.     

肾盂移行上皮癌诊断的影像学评价

目的:探讨3种常用检查方法在肾盂癌诊断中的价值。方法:对经手术病理证实的21例肾盂移行上皮癌,术前均经螺旋CT、超声、静脉肾盂造影检查,各种检查结果均与肿瘤在肾盂内的生长位置和瘤体高度进行对照。结果:静脉肾盂造影直接诊断肾盂移行上皮癌11例,未显影8例,显示正常2例。超声直接诊断肾盂癌13例,发现肾窦分离提示肾盂癌可能2例,未发现异常6例。螺旋CT直接诊断肾盂癌18例,误诊3例。结论:肾盂肿瘤的生长位置主要影响静脉肾盂造影的诊断;肿瘤的高度主要影响超声的诊断,两者具有明显的互补性。无论在肾盂移行细胞癌病灶的发现还是定性方面,螺旋CT的价值明显优于超声和静脉肾盂造影。     

~(14)C-赛诺吉宁在大鼠体内的组织分布和排泄

目的 :研究赛诺吉宁 ( Suanordrin,SR)在大鼠体内过程和药代动力学 ,为临床合理用药提供科学依据。　 方法 :取大鼠 12只 ,雌雄各半 ,经胃灌给 14 C标记的 SR[( 14 C- SR)为 3.7MBq/( 10 mg/ kg) ]后 ,每 2只同性大鼠饲养同一代谢笼中 ,待 12、2 4、72 h及 1、2、3周后 ,采用整体放射自显影等技术测定 SR在大鼠体内组织中的分布和尿、粪、胆汁中的排泄。　 结果 :胃灌药后不同时相的放射自显影图中可见 14 C- SR在胃肠道中的动态分布 ,3周时已消除 ,各时相组织中放射性分布 ,以肝脏为最高 ,依次是肾、心、肺、肾上腺、脾等脏器 ,体内消除较缓慢 ,2 1d内尿粪排泄占给药量的 98.8% ,以尿排泄为主 (占 77.6% ) ,2 4 h内胆汁排泄为 2 8.6% ,以药物原形排泄为主。　 结论 :所测 14 C- SR的层析板上 Rf值其放射性与标准品 14 C- SR相当 Rf值的放射性相符 ,表明该方法灵敏、稳定、特异性好 ;14 C- SR在组织中分布结果与液体闪烁仪测定结果相吻合 ,提示在短时间内多次给药 ,可能会产生蓄积     

Lignoids in insects: chemical probes for the study of ecdysis, excretion and Trypanosoma cruzi-triatomine interactions.

The effects of phytochemicals (lignans and neolignans) are reviewed in a variety of insect species with special focus on the recent advances on feeding, excretion and Trypanosoma cruzi interactions with Rhodnius prolixus. Burchellin, podophyllotoxin, pinoresinol, sesamin, licarin A, and nordihydroguaiaretic acid (NDGA) added to the diet of Rhodnius prolixus larvae induce antifeedant effects only in doses up to 100 microg/ml of blood meal. Additionally, pinoresinol and NDGA significantly inhibit ecdysis (ED(50)<20 microg/ml). Simultaneous application of ecdysone (1 microg/ml) counteracts ecdysial stasis as induced by NDGA in 5th-instar larvae. Experiments in vivo demonstrate that burchellin and podophyllotoxin (100 microg/ml) diminish excretion post-feeding. Simultaneous treatment with 5-hydroxytryptamine (1 mM, 5-HT), a diuretic hormone, partially reverses this effect of burchellin. Experiments in vitro, using isolated Malpighian tubules of R. prolixus, indicate that burchellin (i) decreases diuretic hormone levels in the hemolymph but not the amount of diuretic hormone stored in the thoracic ganglionic masses (including axons); (ii) reduces the volume of urine secreted by isolated Malpighian tubules; and (iii) 5-HT therapy cannot overcome the effect of burchellin on the Malpighian tubules. In R. prolixus fed on blood containing T. cruzi epimastigotes, the number of parasites in the digestive tract decreases drastically in the presence of burchellin and NDGA (10 microg/ml). When these phytochemicals are applied 20 days after T. cruzi infection, burchellin significantly reduces the gut infection, whereas NDGA does not. However, if the insects are pretreated with both compounds 20 days before subsequent infection with epimastigotes, the parasite infection is almost completely abolished. The same holds true when 5th-instar of R. prolixus are inoculated with 0.5 microg/microl/larva of both neolignans 1 day before infection. Taken together, these findings not only provide a better understanding of the lignoid function in insects, but also offer novel insights into basic physiological processes, which make lignoids interesting candidates for new types of insecticides.     

Bcap—37人乳腺癌细胞系对血卟啉衍生物（HPD）的吸收,分布与排泄

本文报道了Bcap—37人乳腺癌细胞系在体内及体外对血卟啉衍生物(HPD)的吸收、分布与排泄。~3H—HPD经腹腔注入载瘤裸鼠体內后48—72小时,其体内分布含量依次为肝脏>脾脏>肾脏>小肠>肿瘤>皮肤>肌肉>脑组织>血液,表明HPD在体内不同器官的分布有差异性,对Bcap—37乳腺癌细胞有一定的亲和力,但并非特异性集聚于肿瘤组织。体外观察到HPD主要分布于Bcap—37乳腺癌细胞胞质内,细胞核对HPD无明显摄取,提示胞质内一些细胞器是光敏损伤的靶部位。     

Pharmacokinetics of stobadin and of the sum of its metabolites in rats during repeated administration

Stobadin dihydrochloride was administered p.o. to rats at a dose of 1 mg kg-1 once daily for 25 consecutive days. The peak and trough concentrations of the sum of stobadin metabolites, determined from Days 6-16 of treatment, demonstrated a steady-state. The mean daily excretion of 3H-radioactivity during this period was 43 per cent and 52 per cent of the administered dose into urine and faeces, respectively. The terminal half-life of stobadin in plasma following a 25-day chronic treatment was 78.3 min, which was shorter than the value of 95.3 min, determined in a single dose experiment. The data indicate that no accumulation of stobadin and of its labelled metabolites occurs in the course of repeated administration of 3H-stobadin.     

三种类型螯合剂对汞在体内分布和排泄影响

小白鼠im~(203)HgCl_2 185kBq/鼠后,立即ip螯合剂,发现在多羧多胺、磷酸、巯基三种类型15个螯合剂中,有7个具有提高排汞的作用,其中以吡哆醇衍生物、半胱氨酸对甲苯磺酸盐及二巯基丁二酸钠(DMS-Na)促排效果较好,分别提高24h尿汞排泄4.6、11.5及22倍,脏器中~(203)Hg含量以DMS-Na组为最低,半胱氨酸对甲苯磺酸盐组次之,但与DMS—Na组相比,相差不显著。     

Comments on the mechanism of excretion of mercury compounds via bile in rats

While an inorganic mercury compound was excreted in rats via bile with substances of high molecular weight only (fraction 1), MeHg and PhHg compounds were excreted with substances of both high and low (fraction 2) molecular weights. The rate of enterohepatic circulation of the compounds increased and their total excretion from rats decreased with the relatively higher content of the compounds in fraction 2. The bile composition was found to be changed as a result of intoxication by organomercury compounds.