Selection of agents for prevention of cisplatin-induced hepatotoxicity.

The objective of this study was to explore the optimal combination of agents used along with cisplatin for protection of hepatotoxicity. Animal experiment was carried out based on the orthogonal design L(8) (2(7)) setting seven factors with two different levels of each, and eight groups of mice were needed. The agents tested in this study were zinc, selenium, fosfomycin, sodium thiosulfate (STS), N-acetyl-cysteine (NAC), methionine and taurine. Mice were supplemented by gavage with various combinations of agents as designed in the orthogonal table once a day for nine days beginning two days before cisplatin administration. 3.5mg/kg body weight of cisplatin was given intraperitoneally once a day for five days simultaneously. After cessation of cisplatin administration, the agents were supplemented continuously for two days. Activities of alanine aminotransferase (ALT) in serum, levels of glutathione (GSH) and malondialdehyde (MDA) in liver were analyzed after cessation of supplementation. Results showed zinc, fosfomycin and methionine were the effective factors for protection of weight loss; fosfomycin and methionine were the effective factors for prevention of decreased liver ratio; selenium, fosfomycin and STS were the effective factors for prevention of increased ALT activities in serum. On the other hand, methionine was the only effective factor for prevention of decreased GSH levels in liver; zinc, selenium and fosfomycin were the effective factors for prevention of increased MDA levels in liver. Based on the data observed in this study, the optimum combinations of agents were selenium, fosfomycin, methionine and taurine, and zinc, selenium, STS and methionine. In conclusion, each agent used in this study could play a beneficial role for prevention of cisplatin hepatotoxicity, however, none could play the crucial role. The potentiated actions for prevention of cisplatin hepatotoxicity could be achieved via combined use of these agents.     

Genetic polymorphisms, messenger RNA expression of p53, p21, and CCND1, and possible links with chromosomal aberrations in Chinese vinyl chloride-exposed workers

This study explores the relationship between genetic polymorphisms of p53, p21, and CCND1, and the susceptibility of chromosomal damage induced by vinyl chloride monomer (CH(2)=CHCl, VCM). Besides gene polymorphisms, we detected the mRNA expression of p53, p21, and CCND1 in VCM-exposed workers and in a control group. One hundred and eighty-three workers occupationally exposed to VCM were investigated. Chromosome damage in peripheral lymphocyte was measured by cytokinesis-block micronucleus assay. The PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53, p21 (exon 2 and exon 3), and CCND1 genes (exon 4). The quantity of gene mRNA expression was detected by real-time PCR (SYBR Green I). Taking into account the effects of genetic polymorphisms, as well as demographic and habitual factors, Poisson regression analysis showed that the risk of chromosomal damage induced by VCM for individuals carrying the p53 intron 6 heterozygous and mutant homozygous genotype was 1.23 times larger (90% confidence interval, 1.01-1.51 P=0.0814), compared with those carrying wild-type homozygous genotypes. The p53 exon 4, intron 3, and intron 6 haplotype pairs of MMM/WWW (M, mutation allele; W, wild allele), and MWM/WWW were associated with increased frequencies of micronuclei. The p53 mRNA expression of VCM-exposed workers was significantly lower than that of nonexposed workers, but p21 mRNA expression in VCM-exposed workers was significantly higher than that of nonexposed workers. Our findings suggest that the p53 intron 6 polymorphism is one of the factors that potentially influence the frequency of micronuclei induced by VCM.     

无髓牙冠内漂白方法的对比研究

目的探讨无髓牙内漂白技术中2种细节操作方法对漂白效果影响。方法选择口腔中前牙和双尖牙区至少2颗变色无髓牙的患者40例,对2颗牙分别采用方法Ⅰ(标准根管治疗后,用光固化玻璃离子封闭根管口,用常温下浸有30%过氧化氢的棉球封闭在髓腔内,3d复诊1次,共封药3次后进行充填治疗)和方法Ⅱ(标准根管预备后,根充前用加热到36℃的30%过氧化氢反复冲洗髓腔,然后做常规根充和充填治疗)治疗。2组均采用同种复合树脂严密充填,1 a后用相同方法观察美观效果和强度效果。结果方法Ⅱ美观效果与强度效果均明显优于方法Ⅰ(P<0.05)。结论漂白变色的无髓牙最好方法是即刻高效的热漂白方法。     

Lateral decubitus HRCT: a simple technique to replace expiratory CT in children with air trapping

OBJECTIVE: To evaluate the effectiveness of lateral decubitus high-resolution CT (HRCT) in detecting air trapping in children. MATERIALS AND METHODS: HRCT scans of 21 children with heterogeneous lung attenuation caused by air trapping (n = 10) or with infiltrative lung disease (n = 11) were reviewed retrospectively. The air-trapping disease included bronchiolitis obliterans (n = 7), bronchial obstruction due to mediastinal lymphoma (n = 1), endobronchial haemangioma (n = 1) and foreign body aspiration (n = 1). HRCT was performed in both lateral decubitus positions as well as the supine position. The attenuation (Hounsfield units; HU) was measured in both the hypo- and adjacent hyper-attenuating areas of the heterogeneous lung portion, and the difference of attenuation between these two areas was calculated in the supine and both lateral decubitus scans, respectively. The attenuation differences of the three scans were compared in each group. RESULTS: The attenuation difference was larger in the ipsilateral decubitus (207.95 +/- 105.24 HU) scans than in the contralateral (121.25 +/- 90.05 HU) or supine (162 +/- 94.01 HU) scans in the air-trapping group (P < 0.05). There were no significant differences among the three scans in the infiltrative lung disease group (P > 0.05). CONCLUSIONS: Lateral decubitus HRCT is an effective adjunct to standard HRCT in the evaluation of air trapping as a cause of mosaic lung attenuation in uncooperative paediatric patients.     

Study on hydrolysable tannin constituents of seed of Juglans regia II

OBJECTIVE: To study hydrolysable tannin constituents of the seed of Juglans regia. METHOD: The chemical constituents were isolated by Diaion HP-20, Toyopaerl HW-40 and MCI gel CHP-20P column chromatogramphy and identified by physicochemical identification and spectral data. RESULT: Six compounds obtained from the 70% ethanol extract were identified as 1, 2, 3, 4, 6-penta-O-galloyl-3-D-glucose (1), rugosin C (2), 1, 2, 3, 6-tetra-O-galloyl-3-D-glugose (3), tellimagrandin II (4), casuarictin (5), 1-degalloylrugosin F (6). CONCLUSION: All compouds were isolated from the seeds of J. regia for the first time.     

大蒜油固体脂质纳米粒中二硫化物和三硫化物在大鼠体内的组织分布

目的：考察大蒜油固体脂质纳米粒(GO-SLN)中二硫化物(DADS)和三硫化物(DATS)在大鼠体内的组织分布。方法：建立了测定大鼠体内大蒜油中二硫化物(DADS)和三硫化物(DATS)的气相-电子捕获法，色谱条件：恒温110 ℃，检测器300 ℃，汽化室180 ℃，载气N2(纯度>99.999％)，流速 1.0 mL·min-1，分流比1∶10；尾吹60 mL·min-1；进样量1 μL。并测定大鼠颈静脉注射GO-SLN和GO注射液后组织中的药物浓度。结果：此色谱条件下各组织的标准曲线、精密度等实验结果表明，该方法适于分析大鼠体内大蒜油中DADS和DATS含量。与GO注射液相比，GO-SLN在大鼠体内的分布特性有不同程度的改变，GO-SLN在各组织中分布均相对较高。结论：SLN能一定程度上提高药物的被动靶向性并延长药物在各组织中的作用时间。     

Death receptor 5 and Bcl-2 protein expression as predictors of tumor response to gemcitabine and cisplatin in patients with advanced non-small-cell lung cancer

The cytotoxic effects of gemcitabine (G) and cisplatin (C) seem to occur through induction of apoptosis. To examine whether the efficacy of GC chemotherapy might be influenced by the expression of death receptor 5 (DR5) and Bcl-2 of the tumor, we investigated the correlation between the tumor response rate and DR5 and Bcl-2 expression in a series of patients prospectively treated with GC. Thirty-four chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) received intravenously 1000 mg/m² gemcitabine on d 1 and 8 along with 80 mg/m² cisplatin on d 2, every 21 d. Tumor specimens were analyzed for DR5 and Bcl-2 expression by immunohistochemistry. The objective response rate was 56% (19 of 34 patients). With median follow-up of 10 mo, the predicted median survival time was 12 mo (95% confidence interval [CI], 9–15 mo). Eleven (32%) and 14 (41%) NSCLC cases were found positive for DR5 and Bcl-2, respectively. The response rate was significantly higher in patients with DR5 expression than those without DR5 expression (91% vs 39%; p=0.008). Patients with Bcl-2 expression were apparently less responsive than those without Bcl-2 expression (21% vs 80%; p=0.001). DR5 and Bcl-2 expression was significantly associated with response to GC chemotherapy. Therefore, DR5 and Bcl-2 status are useful factors for predicting the efficacy of GC.     

Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits

Ribonucleotide reductase (RR) plays a key role in the synthesis of DNA and is the only enzyme responsible for the reduction of ribonucleotides to their corresponding deoxyribonucleotides, providing a balanced supply of precursors for DNA synthesis and repair. There are three known human RR subunits, hRRM1, hRRM2, and p53R2, which is encoded by a p53 target gene. It is not clear whether p53 and RR can directly interact at the protein level to regulate DNA repair. It is also not known where deoxyribonucleotides are synthesized in the cell. In coimmunoprecipitation experiments, we found that hRRM2 and p53R2, but not hRRM1, bound to p53 in KB cells, which express wild-type p53. Moreover, in response to UV irradiation, both p53R2 and hRRM2 were released from p53 and shifted to bind hRRM1. Confocal microscopy confirmed the colocalization of p53 with p53R2 and hRRM2 and the translocation of hRRM1, p53R2 and hRRM2 from the cytoplasm to the nucleus after UV treatment. An in vivo RR activity assay showed that the kinetic profile of increased RR activity was consistent with the accumulation of RR subunits in the nucleus. The ability of p53R2 and hRRM2 to shift from binding p53 to hRRM1 in response to UV irradiation was deficient in the presence of mutant p53. Moreover, in cells overexpressing hRRM2, binding of p53R2 to p53 decreased, whereas binding to hRRM1 increased. Our results suggest that wild-type p53 directly interacts with both p53R2 and hRRM2. In response to UV irradiation, p53R2 and hRRM2 dissociate from p53 and p53R2, and hRRM2 and hRRM1 transfer to the nucleus and form an active RR complex to provide dNDPs for DNA repair. Therefore, the direct interaction of p53 with p53R2 and hRRM2 and the nuclear accumulation of RR subunits after UV exposure might play a pivotal role in DNA repair.     

Growth factor releasing porous poly (ɛ-caprolactone)-chitosan matrices for enhanced bone regenerative rherapy

Drug releasing porous poly(epsilon-caprolactone) (PCL)-chitosan matrices were fabricated for bone regenerative therapy. Porous matrices made of biodegradable polymers have been playing a crucial role as bone substitutes and as tissue-engineered scaffolds in bone regenerative therapy. The matrices provided mechanical support for the developing tissue and enhanced tissue formation by releasing active agent in controlled manner. Chitosan was employed to enhance hydrophilicity and biocompatibility of the PCL matrices. PDGF-BB was incorporated into PCL-chitosan matrices to induce enhanced bone regeneration efficacy. PCL-chitosan matrices retained a porous structure with a 100-200 microm pore diameter that was suitable for cellular migration and osteoid ingrowth. NaHCO3 as a porogen was incorporated 5% ratio to polymer weight to form highly porous scaffolds. PDGF-BB was released from PCL-chitosan matrices maintaining therapeutic concentration for 4 week. High osteoblasts attachment level and proliferation was observed from PCL-chitosan matrices. Scanning electron microscopic examination indicated that cultured osteoblasts showed round form and spread pseudopods after 1 day and showed broad cytoplasmic extension after 14 days. PCL-chitosan matrices promoted bone regeneration and PDGF-BB loaded matrices obtained enhanced bone formation in rat calvarial defect. These results suggested that the PDGF-BB releasing PCL-chitosan porous matrices may be potentially used as tissue engineering scaffolds or bone substitutes with high bone regenerative efficacy.