Secoiridoid glucosides with free radical scavenging activity from the leaves of Syringa dilatata

Activity-guided fractionation of the EtOAc and MeOH extract of the leaves of Syringa dilatata NAKAI furnished one free radical scavenger, the secoiridoid glucoside oleuropein together with ligstroside and an iridoid glucoside, syringopicroside. Oleuropein interacted with the stable free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and showed an IC(50) value of 40.4 microM. L-Ascorbic acid as a positive control showed an IC(50) value of 50.3 microM.     

Four glycosides from the leaves of Abeliophyllum distichum with inhibitory effects on angiotensin converting enzyme

The bioassay-guided fractionation of the n-BuOH extract of Abeliophyllum distichum afforded acteoside (1), isoacteoside (2), rutin (3), and hirsutrin (4). Compounds 1-3 moderately inhibited the angiotensin I converting enzyme activity in a dose-dependent manner. Compounds 1-3 showed the 50% inhibitory concentration values of 228 micro g/mL, 290 micro g/mL, and 278 micro g/mL, respectively.     

Genetic effects on urinary 1-hydroxypyrene levels in a Korean population

Urinary 1-hydroxypyrene (1-OHP) has been used as a biomarker for assessing the level of exposure to environmental carcinogenic polycyclic aromatic hydrocarbons (PAHs). In order to perform the appropriate biological monitoring for examining the level of exposure to PAHs, this study investigated whether or not genetic polymorphisms of the metabolic enzymes, which might be involved in the metabolism of pyrene, affected the urinary 1-OHP levels in a population of 661 Koreans (male, 63%; female, 37%; mean age, 36.5 +/- 11.1 years) who were not occupationally exposed to PAHs. Urinary 1-OHP was detected in 76% of the subjects (range 0.001-3.8 micro g/l). Among the physical and lifestyle factors, cigarette-smoking was found to be associated with the urinary 1-OHP levels (P < 0.05). After adjusting for these factors, we found that the GSTT1 genotypes affected the urinary 1-OHP levels, i.e. the GSTT1 present subjects had approximately 1.5 times the urinary 1-OHP level than the GSTT1 null subjects (P < 0.05). In the case of the subjects who were also GSTM1 null, this trend became stronger, i.e. the GSTT1 present subjects had approximately 2 times the urinary 1-OHP level (P < 0.01). However, the genetic polymorphism of the other metabolic enzymes, cytochrome P-450 (CYP)1A1, CYP1B1 and GSTM1 alone, did not affect the urinary 1-OHP level. Therefore, this study suggests that the GSTT1 genetic polymorphism has the potential to affect the biological monitoring of PAHs with urinary 1-OHP, and might act as a genetic factor in PAH-related toxicity.     

大鼠肺鳞癌癌变过程中凋亡和增殖相关基因表达的研究

背景与目的:细胞凋亡信号转导的关键是凋亡下游蛋白caspase-3的激活。有关caspase-3与人类非小细胞肺癌的研究已取得了很大的进展,但它与大鼠肺鳞癌的关系的研究未见报道。本研究探讨大鼠肺鳞癌癌变过程中细胞增殖与凋亡相关基因cas-pase-3和增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)的表达在癌变过程中的作用。方法:取60只Wistar大鼠,其中50只用化学致癌物3-甲基胆蒽(3-methylcholanthrene,MCA)及二乙基亚硝胺(diethyinitrosamine,DEN)碘油溶液于左肺叶支气管灌注以诱发大鼠肺鳞状细胞癌;另10只灌注碘油作为对照。用免疫组织化学SP法检测癌变过程中caspase-3和PCNA蛋白的表达;TUNEL法检测凋亡细胞。结果:对照组大鼠支气管粘膜上皮、癌前病变和肺鳞癌中,caspase-3蛋白表达的阳性评分均值分别为3.10±0.99、2.25±1.13、1.38±0.95;PCNA的平均增殖指数(PCNA-LI)分别为:14.10±5.02、28.13±8.72、41.88±14.24;平均凋亡指数(AI)分别为:0.60±0.52、2.06±0.85、2.26±1.14。肺鳞癌与对照组大鼠支气管粘膜上皮相比,其caspase-3蛋白阳性表达的差异有非常显著性(P<0.01),与癌前病变相比其caspase-3阳性表达的差异有显著性(P<0.05)。对照组大鼠支气管粘膜上皮为低增殖指数和低凋亡指数,分别与后     

Torilin from Torilis japonica,as a new inhibitor of testosterone 5 alpha-reductase

The methanolic extract of the fruits of Torilis japonica showed a potent inhibition against 5 alpha-reductase activity in vitro. Bioassay-guided fractionation of the methanol extract of the fruits followed by repeated silica gel chromatography led to the isolation of an active principle and its structure was identified as torilin on the basis of spectroscopic data. Torilin (IC50 = 31.7 +/- 4.23 microM) showed a stronger inhibition of 5 alpha-reductase than alpha-linolenic acid (IC50 = 160.3 +/- 24.62 microM) but was weaker than finasteride. (IC50 = 0.38 +/- 0.06 microM). Simple guaiane-type compounds, such as (-)-guaiol and guaiazulene showed weak inhibitory effects on the 5 alpha-reductase activity with IC50 values of f 81.6 microM and 100.8 microM, respectively, while azulene was not active. These results suggest that both degrees of unsaturation and the side-chain in the guaiane skeleton are important for the manifestation of 5 alpha-reductase inhibition.     

A High-Throughput Combinatorial Approach for the Discovery of a Cremophor EL-Free Paclitaxel Formulation

Purpose. The purpose of this work was to replace Cremophor-EL in the commercial paclitaxel intravenous formulation, Taxol®, using a novel high-throughput combinatorial formulation approach. Methods. Full factorial combinations of 12 generally regarded as safe excipients at three different concentrations were screened using an automated liquid dispenser. The hit formulations were further optimized to give the final optimized formulation TPI-1. TPI-1 was then tested in rats to compare its pharmacokinetic profile to Taxol®. Results. Of the 9,880 combinations tested in the initial screen, 19 were identified as hit combinations. These were further optimized to give the final formulation TPI-1. When tested in rats, TPI-1 was well tolerated at both the low and high doses of 5 mg/kg and 10 mg/kg, whereas Taxol® killed all the rats at the high dose. TPI-1 experienced slower elimination compared to Taxol®. Similar to Taxol®, TPI-1 also exhibited nonlinear pharmacokinetics. Conclusions. This study demonstrated the power of a high-throughput combinatorial approach for alternative paclitaxel formulations. We believe that this approach can be applied to drug formulation in general and it can improve the speed and efficiency of drug formulation design.     

Optical detection and eradication of dysplastic Barrett's esophagus

Dysplastic Barrett's esophagus is a condition that offers multiple diagnostic and therapeutic challenges. The diagnosis of dysplasia within Barrett's esophagus currently relies on periodic endoscopic surveillance with multiple biopsies, a methodology limited by random sampling error, inconsistent histopathologic interpretation and delay in diagnosis. Optical spectroscopic and imaging techniques have the potential to identify dysplastic or early neoplastic lesions in real-time. These diagnostic modalities are needed to enhance the endoscopic surveillance of Barrett's esophagus in the future as well as help to define lesions for endoscopic therapy. Esophagectomy has been the standard of care for Barrett's esophagus with high-grade dysplasia although it is a procedure associated with significant morbidity and mortality. Minimally invasive endoscopic ablative therapies are attractive and less morbid alternatives to esophagectomy, with promising results obtained from the use of light-activated drugs (i.e., photodynamic therapy). The combination of novel optical diagnostic techniques and therapies will provide the endoscopist with much needed tools that can considerably enhance the management of patients with Barrett's esophagus. This article reviews the current status and future prospects of optical-based modalities for diagnosis and therapy of dysplastic Barrett's esophagus.     

Remineralizing effects of glass ionomer restorations on adjacent interproximal caries

The purpose of this study was to examine the in vitro remineralization of incipient caries lesions on teeth adjacent interproximally to teeth with Class II glass ionomer cement restorations. Sixty-four extracted molars were selected and 1 x 5 mm artificial caries lesions were created at the interproximal contact point. One hundred micrometer sections were obtained at the caries sites, and polarized-light photomicrographs were obtained. The sections were covered with varnish, leaving only the external section site exposed, and were placed back into the original tooth. In another sixty-four molars, Class II cavities were prepared. Equal numbers of preparations were filled with Fuji IX GP, Vitremer, Ketac-Molar, or Z 250. These sixty-four teeth were mounted to have interproximal contact with the adjacent teeth containing the artificial caries lesions. Specimens were placed in closed environments of artificial saliva for one month. After thirty days, the same sections were photographed again under polarized light, and areas of the lesions were quantitated. Decrease in the size of caries lesions indicated the glass ionomers had significantly greater remineralization effects on adjacent caries than the nonfluoridated composite resin (ANOVA p < 0.05). There were no significant differences among the three glass ionomers tested.