Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.     

高脂血症时血清二乙基对硝基苯磷酸酯酶活性的变化

目的 :研究tritonWR 13 3 9致小鼠高脂血症时血清二乙基对硝基苯磷酸酯酶 (ParaoxonaseI ,PON 1)活性的变化及PON 1活性与血浆脂质含量之间的关系。方法 :在小鼠尾静脉注射tritonWR13 3 9后的 3h ,6h ,12h ,2 4h ,48h ,72h ,眼球摘除术取血 ,用酶标法测定小鼠血浆总胆固醇 (TC) ,甘油三酯 (TG ) ,高密度脂蛋白 -胆固醇 (HDL -C) ,载脂蛋白AI (ApoAI) ,载脂蛋白B (ApoB含量 ) ,并计算出ApoAI/ApoB ,HDL -C/TC比值 ,用分光光度计法测定PONI活性。结果 :TritonWR 13 3 9尾静脉注射后 3h ,小鼠血浆TC和TG含量即急剧增高 ,与对照组相比 ,P <0 .0 1,分别在注射后 2 4h和 3h达到峰值 ,随后逐渐下降 ,其中血浆TG含量在注射后 48h即恢复正常水平。tritonWR13 3 9尾静脉注射后 3h ,小鼠血浆HDL -C和ApoB含量急剧增高 ,与对照组相比 ,P <0 .0 5,分别在注射后 2 4h和 6h达到峰值 ,随后逐渐下降 ,分别在注射后 48h和 72h恢复正常水平。tritonWR13 3 9尾静脉注射后 3h ,小鼠血浆ApoAI含量即急剧降低 ,与对照组相比 ,P <0 .0 5,随后逐渐增高 ,在注射后 6h即恢复正常水平。tritonWR 13 3 9尾静脉注射后 3h ,小鼠血浆ApoAI/ApoB和HDL-C/TC比值减少 ,与对照组相比 ,P <0 .0 1,随后逐渐增高 ,其中ApoAI/ApoB比值在 72h恢复     

E838等抗放药对放射损伤防治作用的比较

目的；比较研究E838，WR－2721，盐酸胱胺和炔雌醇等对放射损伤的防治作用及其相互之间的协同作用关系。方法：采用小鼠腹腔注射或灌胃的方法在致伤前或／和致伤后按常用量给药，观察30d存活率，死亡动物平活日和保护系数K的差异。结果：（1）致伤前预防给药，上述4种药物均明显提高了放射损伤的存活率，并延长了死亡动物的平均存活日，其中以E838和WR2721效果最佳；（2）致伤后给药则仅E838和茜草显示了治疗效果；（3）联合用药实验显示所研究的5种配伍用药方式均有较好的防治效果，但以WR2721（防）＋E838（治）效果最好。结论：E838和WR2721与其它抗放药相比具有较理想的辐射防护作用，且E838还有一定的治疗作用,两者合理配伍使用可发挥协同的作用效果。     

E838等5种辐射防护药对放烧复合伤防治作用的实验观察

目的 比较研究E838、WR-2721茜草、盐酸胱胺和炔雌醇等5种辐射防护药对放射损伤和放烧复合伤的防治作用及其相互间的协同作用。方法 采用小鼠腹腔注射、灌胃的方法在致伤前/或和致伤后按常用量给药,观察30d存活率,死亡动物平均存活日和保护系数K的差异。结果 （1）致伤前预防给药,5种药物均明显提高了放射损伤和放烧复合伤的存活率,并延长了死亡动物的平均存活日,其中以E838和WR-2721效果最佳;（2）致伤后给药则仅E838和茜草显示了治疗效果;（3）联合用药实验显示所研究的5种配伍用药方式均有较好的防治效果。但以WR-2721 E838治效果最好。结论 E838和WR-2721与其它辐射防护药相比具有较理想的辐射防护作用,且E838还有一定的治疗作用。两者合理配伍可发挥协同治疗作用。     

Effect of North American ginseng on 137Cs-induced micronuclei in human lymphocytes: a comparison with WR-1065

To explore the radioprotective effect of a standardized North American ginseng extract (NAGE) on human peripheral blood lymphocytes (PBL), a micronuclei (MN) assay was conducted in PBL obtained from 12 volunteers. NAGE (50-1000 microg/mL) and WR-1065 (1 mM and 3 mM) were applied to PBL cultures at 0 h and 90 min post-irradiation. It was found that (1) the baseline MN yield of PBL ranged from 14.4 +/- 1.5 to 15.9 +/- 1.5 per 1000 binucleated cells (p > 0.05); after irradiation (1 Gy and 2 Gy), the MN yield increased sharply; (2) MN yields declined with increasing concentrations of NAGE and WR-1065. Even at 90 min post-irradiation of 1 Gy, the maximum level of MN reduction rate caused by NAGE and WR-1065 was 53.8% and 59.2%, respectively; after 2 Gy irradiation, it was 37.3% and 42%, respectively; (3) the MN distribution in PBL followed a non-Poisson distribution in all cases; and (4) both NAGE and WR-1065 showed no significant effect on the proliferation index of lymphocytes. The results indicate that NAGE is a relatively non-toxic natural product, which can be administered as a dietary supplement and has the potential to be a radiation countermeasure.     

Effect of lysosomal loading with Triton WR 1339 on the distribution of albumin-14C in the liver of rats with chronic hepatitis

The mechanism of the protective effect of the lysosomotropic detergent Triton WR 1339 in chronic hepatitis was examined. Assuming that the improvement in the condition is connected with potentiation of the heterophagous function of the lysosomes, the intensity of uptake of albumin-¹⁴C by the liver and its subcellular distribution in the liver of rats were studied during administration of the detergent to animals with chronic carbon tetrachloride hepatitis. Preliminary injection of the detergent did not affect the intensity of uptake of albumin-¹⁴C, but subsequent injection of Triton WR 1339 into rats with toxic hepatitis reduced the protein uptake to values obtained in intact rats. In chronic hepatitis albumin-¹⁴C is concentrated in the lysosomal fraction. After injection of Triton WR 1339 into the poisoned animals the peaks of labeled protein and lysosomal enzymes did not coincide. The selective role of lysosomes of the Kupffer cells of the liver in producing the more rapid recovery of the liver from chronic hepatitis is examined.Presented by Academician of the Academy of Medical Sciences of the USSR V. P. Kaznacheev.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 7, pp. 816–819, July, 1976.     

Vaccinia virus-induced smallpox postvaccinal encephalitis in case of blood-brain barrier damage

Smallpox vaccination is the only currently effective mean to combat the threat of variola virus used as a bioterrorism agent, although it is responsible for a rare but serious complication, the postvaccinal encephalitis (PVE). Development of safer vaccines therefore is a high priority as the PVE physiopathology is not well understood to date. If vaccinia virus (VACV) is responsible for PVE by central nervous system (CNS) dissemination, trans-migration of the VACV across the blood-brain barrier (BBB) would be supposed to be essential. Given the complexity of the pathogenesis of vaccinia neurovirulence, an in vitro BBB model was used to explore the mechanism of VACV to induce BBB permeability. Two VACV strains were studied, the neurovirulent Western Reserve strain (VACV-WR) and the vaccine reference Lister strain (VACV-List). A mouse model was also developed to study the ability of these two viral strains to propagate in the brain from the blood compartment, their neurovirulence and their neuropathogenesis. In vitro, the loss of permeability resulted from the tight-junctions disruption was induced by virus replication. The ability of VACV to release infectious particles at the abluminal side suggests the capacity of both VACV strains to migrate across the BBB from the blood to the CNS. In vivo, the virus replication in mice CNS was strain-dependent. The VACV-WR laboratory strain proved to be neuroinvasive and neurovirulent, whereas the VACV-List strain is safe in physiological conditions. Mice PVE was observed only with VACV-WR in the co-infection model, when BBB opening was obtained by lipopolysaccharide (LPS) treatment. This study suggests that VACV is able to cross the BBB but encephalitis occurs only in the presence of a co-infection by bacteria. So, a model of co-infection, mimicked by LPS treatment, could have important implication towards the assessment of neurovirulence of new vaccines.     

补中益气丸低剂量辐射防护作用的实验研究

目的探讨补中益气丸对3Gyγ射线辐射小鼠的保护作用。方法将60只小鼠随机分为正常组、辐射组、阳性药氨磷汀（WR2721）组、补中益气丸低、中、高剂量组。除正常组外其余各组接受3Gy60Coγ射线照射,观察各组小鼠外周血象变化。结果与辐射组比较,WR2721组在照射后1、5、9、12、16、20、27、31、34d白细胞数显著升高（P〈0．05,P〈0．01）,补中益气丸中剂量组（2．34g·k^-1）在5、9、20、27、31、34d白细胞（WBC）数显著提高（P〈0．05,P〈0．01）,补中益气丸低剂量组（1．17g·kg^-1）在20、27、31d时WBC数提升（P〈0．05,P〈0．01）,补中益气丸高剂量组（4．68g·kg^-1）在20d时WBC数显著提升（P〈0．05）。血小板（PLT）值与辐射组比较,WR2721组和补中益气丸高剂量组在照射后1d显著性减轻辐射对PLT的损伤（P〈0．01）。结论补中益气丸各剂量组能显著提升辐射损伤小鼠外周血WBC数,高剂量组能减缓并减轻外周血中PLT的损伤,补中益气丸具有低剂量叮射线辐射防护作用。