The involvement of serotonergic system in the antidepressant effect of zinc in the forced swim test

Recent preclinical data indicated the antidepressant-like activity of zinc in different tests and models of depression. The present study investigates the involvement of the serotonergic system in zinc activity in the forced swim test (FST) in mice and rats. The combined treatment of sub-effective doses of zinc (hydroaspartate, 2.5 mg Zn/kg) and citalopram (15 mg/kg), fluoxetine (5 mg/kg) but not with reboxetine (2.5 mg/kg) significantly reduces the immobility time in the FST in mice. These treatments had no influence on the spontaneous locomotor activity. Moreover, while the antidepressant-like effect of zinc (5 mg/kg) in the FST was significantly blocked by pretreatment with inhibitor of serotonin synthesis, p-chlorophenylalanine (pCPA, 3 × 200 mg/kg), 5HT-2_A/C receptor antagonist, ritanserin (4 mg/kg) or 5HT-1A receptor antagonist, WAY 1006335 (0.1 mg/kg), the zinc-induced reduction in the locomotor activity was not affected by these serotonin modulator agents. These results indicate the specific involvement of the serotonergic system in antidepressant but not the motion behavior of zinc in mice. Also, an increase in the swimming but not climbing parameter of the rat FST observed following zinc administration (2.5 and 5 mg Zn/kg) indicates the serotonin pathway participation. This present data indicates that the antidepressant-like activity of zinc observed in the FST involves interaction with the serotonergic system.     

RIT2 variant is not associated with Parkinson's disease in a Taiwanese population

Recent genome-wide association studies of Parkinson's disease (PD) have identified the rs12456492 variant of the novel susceptibility loci, RIT2, as being associated with disease risk in a large white population. Studies among Asians are scarce. We genotyped RIT2 rs12456492 variant in a total of 1000 participants, comprising 500 patients with PD and 500 control subjects in a Taiwanese population. The frequency of GA/AA genotype was slightly higher in PD patients compared with controls, but was without statistical significance (odds ratio = 1.03, 95% confidence interval = 0.73–1.46, p = 0.86). We failed to replicate the RIT2 rs12456492 variant as a genetic risk factor for PD in our population.     

Detection of Early Pregnancy Factor-Like Activity in Women With Gestational Trophoblastic Tumors

ABSTRACT: The presence of immunosuppressive early pregnancy factor (EPF) in the maternal serum has so far been associated with gestation. Its presence in the serum of women with gestational trophoblastic tumors was investigated. The results indicate that while EPF activity was detected in the serum of women with choriocarcinoma, no such activity was detected in the serum of women with hydatidiform mole, leading to the novel use of EPF as a marker to distinguish these two clinical situations. Results of the experiments also suggest that EPF moiety present in the maternal serum during pregnancy may be of different molecular entity than that present in the serum of women with choriocarcinoma.     

RIT1基因在肝细胞癌中的扩增及其临床意义

背景与目的:已有的研究显示肝细胞癌的染色体1q有高频扩增,1q21-22是最小的高频扩增区带之一,可能存在肝细胞癌相关的候选癌基因。RIT1基因位于1q21.3区带,是Ras的亚家族成员,RIT1蛋白在分子结构和功能方面与Ras蛋白非常相似,推测RIT1基因可能是肝细胞癌的候选癌基因之一。因此,本研究通过检测肝细胞癌RIT1基因的扩增情况,并与临床指标相联系,探讨该基因对肝细胞癌发生和发展的可能作用。方法:建立荧光定量PCR的方法,在PEABI7000型荧光定量PCR仪上检测43例肝细胞癌患者手术切除的癌组织及远癌肝组织RIT1基因的拷贝数,并用癌组织与癌旁肝组织基因拷贝数的比值作为RIT1基因的扩增倍数。结果:在43例肝细胞癌患者中,11例有RIT1基因的扩增,扩增率为25.6%;将基因扩增组与非扩增组比较,基因扩增组的生存期(平均15个月)明显短于非扩增组(平均34个月),P=0.0009,且在病理分级和肝硬化程度方面也具有明显的差异,P<0.01。结论:基因扩增可能是癌基因RIT1在肝细胞癌的激活方式之一,该基因的扩增可能对肝细胞癌的发生发展起一定的作用。     

Therapeutic options for recurrent malignant glioma

Background and purpose: Despite the given advances in neuro-oncology most patients with high grade malignant glioma ultimately fail locally or locoregionally. In parallel with improvements of initial treatment options, several salvage strategies have been elucidated and already entered clinical practice. Aim of this article is to review the current status of salvage strategies in recurrent high grade glioma. Material and methods: Using the following MESH headings and combinations of these terms the pubmed database was searched: “Glioma”, “Recurrence”, “Neoplasm Recurrence, Local”, “Radiosurgery”, “Brachytherapy”, “Neurosurgical Procedures” and “Drug Therapy”. For citation crosscheck the ISI web of science database was used employing the same search terms. In parallel, the abstracts of ASCO 2008-2009 were analyzed accordingly. Results: Currently the following options for salvage entered clinical practice: re-resection, re-irradiation (stereotactic radiosurgery, (hypo-)fractionated (stereotactic) radiotherapy, interstitial brachytherapy) or single/poly-chemotherapy schedules including new dose-intensified or alternative treatment protocols employing targeted drugs. Re-operation is associated with high morbidity and mortality, however, is an option in a highly selected patient cohort. Since toxicity has been overestimated, re-irradiation is an increasingly used option with precise fractionated radiotherapy being the most optimal technique. On average, time to secondary progression is in the range of several months. Conventional chemotherapy regimens also improve time to secondary progression; however the efficacy is only modest and treatment-related toxicities like myelo-suppression occur very frequently. Molecular targeted agents/kinases are undergoing clinical testing; however no final recommendations can be made. Conclusions: Currently, several re-treatment options with only modest efficacy exist. The relative value of each approach compared to other options is unknown as well as it remains open which sequence of modalities should be chosen.     

Activity estimation in radioimmunotherapy using magnetic nanoparticles

Objective:Estimation of activity accumulated in tumor and organs is very important in predicting the response of radiopharmaceuticals treatment.In this study,we synthesized ¹⁷⁷Lutetium(¹⁷⁷Lu)-trastuzumabiron oxide nanoparticles as a double radiopharmaceutical agent for treatment and better estimation of organ activity in a new way by magnetic resonance imaging（MRI）.Methods:¹⁷⁷Lu-trastuzumab-iron oxide nanoparticles were synthesized and all the quality control tests such as labeling yield,nanoparticle size determination,stability in buffer and blood serum up to 4 d,immunoreactivity and biodistribution in normal mice were determined.In mice bearing breast tumor,liver and tumor activities were calculated with three methods:single photon emission computed tomography（SPECT）,MRI and organ extraction,which were compared with each other.Results:The good results of quality control tests（labeling yield:61%±2%,mean nanoparticle hydrodynamic size:41±15 nm,stability in buffer:86%±5%,stability in blood serum:80%±3%,immunoreactivity:80%±2%） indicated that ¹⁷⁷Lu-trastuzumab-iron oxide nanoparticles could be used as a double radiopharmaceutical agent in mice bearing tumor.Results showed that ¹⁷⁷Lu-trastuzumab-iron oxide nanoparticles with MRI had the ability to measure organ activities more accurate than SPECT.Conclusions:Co-conjugating radiopharmaceutical to MRI contrast agents such as iron oxide nanoparticles may be a good way for better dosimetry in nuclear medicine treatment.     

Comparison of Rinkel injection therapy with standard immunotherapy

We compared the results of a controlled, double blind study of standard immunotherapy (SIT) in subjects with ragweed hay fever during 1980 with the results of our study of Rinkel injection therapy (RIT) in a group of subjects with ragweed hay fever in 1979. Both groups were of comparable sensitivity. During the 1980 hay fever season in Milwaukee, 20 subjects with atopic rhinitis due to ragweed pollen (eight from the 1979 group treated with RIT) were given SIT (Tr), while 14 matched subjects (eight from the 1979 placebo group) were treated with a histamine placebo (Pl). The same glycerinated aqueous ragweed extract and glycerinated histamine placebo were used in both studies. The mean cumulative dose of ragweed extract in the 1980 study was 5391 PNU (20.1 μg of antigen E [AgE]) as compared with 41.5 PNU (0.16 μg of AgE) in 1979. Results indicated a significantly lower weekly mean symptom score (SxSc) in the Tr group compared with that of the Pl group in 5 of the 6 wk that ragweed pollen was counted in 1980. Weekly mean medication score (MxSc) and physical exanination score (PESc) showed similar but less striking differences. The mean seasonal SxScs, MxScs, and PEScs of the SIT Tr group were significantly lower than those of the Pl group in 1980 as well as those of the RIT Tr group in 1979. The same indices were also significantly lower in 1980 by paired analyses in the subset of eight subjects treated in both years. RAST scores showed a significant decrease in the “after season” means in the Tr group as compared with the Pl group in 1980 but not in 1979 (analysis of covariance). We conclude that SIT is more effective than a placebo or RIT in reducing SxSc, MxSc, and PESc as well as in diminishing postseason RAST values. We cannot recommend therapy as proposed by Dr. H. J. Rinkel for clinical use at this time.     

抗人肝癌单克隆抗体的人体放射免疫定位及治疗

研究单抗Ｈｅｐａｍａ－Ⅰ在原发性肝癌患者中的导向定位及治疗效果。方法本研究包括３０个失去手术指征的原发性肝癌患者,其中１８例行放射免疫显像（ＲＩ）研究,１２例行放射免疫治疗（ＲＩＴ）研究,分别从肝动脉投与１３１Ｉ－ＨｅｐａｍａＩ９．２５ＧＢｑ（ＲＩ）及１８．５ＧＢｑ（ＲＩＴ）。结果接受该制剂后未见明显毒性反应,显像率为１４／１８,最佳显像时间在注射后９６小时,ＡＦＰ下降率为７５．０％,肿瘤部分缩小率６６．６％,与对照组比较,生存时间明显延长。结论单抗ＨｅｐａｍａＩ能在人体内认识原发性肝癌细胞,并能与之特异结合。核素碘标记的ＨｅｐａｍａＩ可作为治疗晚期肝癌的综合疗法之一。