银杏内酯B注射液大鼠药代动力学研究

目的:研究大鼠静脉注射银杏内酯B注射液后的药代动力学。方法:采用LC-MS法测定银杏内酯B经时血药浓度,采用DAS2.0实用药代动力学程序计算其药代动力学参数。结果:大鼠单次静脉注射低、中、高(0.75、3.75、14.0 mg/kg)三个剂量银杏内酯B注射液,银杏内酯B主要药代动力学参数:Tmax均为(0.083±0)h,Cmax均值分别为(422.312±14.203)、(1608.467±226.677)、(1987.036±237.202)μg/L,AUC0-t均值分别为(533.833±114.943)、(1786.029±137.066)、(1943.44±415.892)μg.h/L。结论:各剂量组血药浓度试验数据经拟和优度分析,药物消除符合三室模型,AUC0-t、AUC0-∞、Cmax随剂量的增加而不成比例增加,说明银杏内酯B注射药液给药后在大鼠体内呈非线性动力学消除过程。     

Is functional state of spinal microglia involved in the anti-allodynic and anti-hyperalgesic effects of electroacupuncture in rat model of monoarthritis?

Spinal microglia play a key role for creating exaggerated pain following tissues inflammation or injury. Electroacupuncture (EA) can effectively control the exaggerated pain both in humans with inflammatory disease and animals with experimental inflammatory pain. However, little is known about the relationship between spinal glial activation and EA analgesia. Using immunohistochemistry, RT-PCR analysis, and behavioral testing, the present study demonstrated that (1) Unilateral intra-articular injection of CFA produced a robust microglial activation and the up-regulation of the tumor necrosis factor (TNF)-alpha, interleukin (IL-1beta), and IL-6 mRNA levels in the spinal cord; (2) Repeated intrathecal (i.t.) injection of minocycline (100 microg), a microglial inhibitor, or EA stimulation of ipsilateral "Huantiao"(GB30) and "Yanglingquan" (GB34) acupoints significantly suppressed CFA-induced nociceptive behavioral hypersensitivity and spinal microglial activation; (3) Combination of EA with minocycline significantly enhanced the inhibitory effects of EA on allodynia and hyperalgesia. For the first time, these data provide direct evidence for the involvement of spinal microglial functional state in anti-nociception of EA. Thus, anti-neuroinflammatory effect of EA might be considered as one of the mechanisms of its anti-arthritic pain effects, and thereby a multidisciplinary integrated approach to treating symptoms related to arthritis might be raised.     

测定胃肠道恶性肿瘤和肺癌组织中u—PA的意义

本文建立了测定微量尿激酶型纤溶酶原激活物(u-PA)抗原的ELISA法,检测35例胃肠道恶性肿瘤如胃、食道、结肠、直肠癌以及肺癌患者的癌组织与癌邻近组织的u-PA含量,结果各种癌组织的u-PA明显增高(P<0.05～0.01)。同时测定组织纤溶酶原激活物(t-PA)抗原,仅胃癌组织有明显增高(P<0.01),纤溶酶原激活物(PA)的活性增高见于胃、结肠和直肠癌组织(P<0.05～0.001)。提示这些恶性肿瘤细胞产生或分泌PA抗原特别是u-PA增多,使局部纤溶活性增强,是促进癌细胞增殖和转移的机制之一。     

Effects of antireflux treatment on bronchial hyper-responsiveness and lung function in asthmatic patients with gastroesophageal reflux disease

AIM: To investigate the effects of antireflux treatment on bronchial hyper-responsiveness and lung function in asthmatic patients with gastroesophageal reflux disease(GERD).METHODS: Thirty asthmatic patients with GERD were randomly divided into two groups (group A and group B).Patients in group A (n=15) only received asthma medication including inhaled salbutamol 200μg four times a day and budesonide 400μg twice a day for 6 weeks. Patients in Group B (n=15) received the same medication as group A,and also antireflux therapy including oral omeprazole 20mg once a day and domperidone 10mg three times a day for 6 weeks. Pulmonary function tests and histamine bronchoprovocation test were performed before and after the study.RESULTS: There was no significant difference in the baseline values of pulmonary function and histamine PC2FEV1 between the two groups. At the end of the study, the mean values for VC, VC%, FVC, FVC%, FEV1, FEV1%, PEF, PEF%, PC20-FEV1 were all significantly improved in group B, compared with group A.CONCLUSION: Antireflux therapy may improve pulmonary function and inhibit bronchial hyper-responsiveness in asthmatic patients with GERD.     

Effect of cell fusion on metastatic ability of mouse hepatocarcinoma cell lines

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Effects of Copper and Cadmium on Lipogenic Metabolism and Metal Element Composition in the Javelin Goby (Synechogobius hasta) After Single and Combined Exposure

The present study was performed to determine the effects of single and combined exposure of copper (Cu) and cadmium (Cd) on lipogenic metabolism and metal element composition of javelin goby Synechogobius hasta. Two hundred and forty uniform-sized S. hasta (initial mean weight 20.3 ± 0.3 g [mean ± SEM throughout]; initial body length 15.2 ± 0.2 cm) were randomly assigned to 12 fiberglass tanks (water volume 300 l) with 20 fish/tank. The fish were exposed to four treatments with different Cu and Cd concentration for 30 days, respectively: (1) control (without extra Cu and Cd addition), (2) Cu (nominal concentrations of 77 μg/l), (3) Cd (79 μg/l), and (4) Cu + Cd (Cu/Cd coexposure). Growth decreased, but hepatosomatic index, viscerosomatic index, and lipid content increased after metal exposure. Staining with Oil Red O and haematoxylin and eosin showed extensive alterations in liver of metals-exposed fish. Metal exposure influenced the accumulation of metal elements (Cu, Cd, iron, zinc, and manganese) in several tissues (muscle, gill, intestine, liver, and spleen) and increased hepatic 6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, malic enzyme, isocitrate dehydrogenase, and fatty acid synthase activities. The results of the present study indicated that the changes in lipogenic metabolism and metal element compositions of fish under Cu and Cd coexposure could not be explained by synergism of the addition of the effects observed in singly Cu- or Cd-exposed fish. To our knowledge the present study, for the first time, investigated the effects of Cu and Cd coexposure on hepatic lipogenic metabolism and metal element compositions in a wide range of tissues and organs in fish, which provided new evidence for Cu and Cd interactions in fish.     

Protective Effects of Calcium Pre-Exposure Against Waterborne Cadmium Toxicity in Synechogobius hasta

The present study was performed to evaluate the effects of calcium (Ca) pre-exposure and then waterborne cadmium (Cd) exposure on metal element accumulation, enzymatic activities, histology, and ultrastructure in Synechogobius hasta and test the hypothesis that Ca could protect against Cd-induced toxicity in the fish species. Three hundred sixty fish [initial mean weight 25.5 ± 0.1 g (mean ± SEM)] were stocked in 18 circular fiberglass tanks (water volume: 300 l), 9 of which were pre-exposed to Ca at a rate of 400 mg Ca/l for 9 days and then exposed to concentrations of 0, 79.3, and 158.6 μg Cd/l for 9 days. Another 9 tanks were cultured in natural seawater (no extra Ca addition) for 9 days and then exposed to concentrations of 0, 79.3, and 158.6 μg Cd/l for 9 days. Both Ca pre-exposure and then waterborne Cd exposure influenced the accumulation of metal elements [cadmium (Cd), copper, zinc, and iron] in several tissues (muscle, gill, liver, spleen, and intestine), changed hepatic intermediary metabolism, and induced histological and ultrastructural alterations in tissues. In general, Ca pre-exposure seemed to mitigate the severity of Cd-induced mortality and histopathological injuries indicating that Ca pre-exposure had the capacity to decrease Cd toxicity in S. hasta.     

In Vitro Effects of Selenium on Copper-Induced Changes in Lipid Metabolism of Grass Carp (Ctenopharyngodon idellus) Hepatocytes

The present study was performed to evaluate the in vitro effects of selenium (Se) supplementation to prevent copper (Cu)-induced changes in lipid metabolism of hepatocytes from grass carp (Ctenopharyngodon idellus). Four groups (control and 100 μM Cu in combination with 0, 5, and 10 μM Se, respectively) were chosen. Compared with the control, activities of glucose 6-phosphatedehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme, and carnitine palmitoyltransferase I (CPT I) of all three Cu-exposed groups at 24 and 48 h were significantly greater. However, among three Cu-exposed groups, increasing Se concentration tended to increase activities of G6PD and ME at 24 h and 6PGD activity at 24 and 48 h but decreased CPT I activity at 24 h. Compared with the control, Cu exposure alone, or in combination with Se, downregulated mRNA levels of sterol regulatory element-binding protein-1 (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase, peroxisome proliferator activated receptor alpha (PPARα), CPT I, and hormone-sensitive lipase (HSL) at 24 h as well as SREBP-1c, FAS, and ACC mRNA levels at 48 h. However, upregulated mRNA levels of PPARα, CPT I, and HSL, as well as decreased triglyceride content, were recorded at 48 h. Thus, although toxic at greater levels, lower levels of Se provided significant protection against Cu-induced changes in lipid metabolism. For the first time, our study indicates the dose- and time-dependent effects of Se addition on changes in lipid metabolism induced by Cu in fish hepatocytes and provides new insights into Se–Cu interaction at both enzymatic and molecular levels.