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| 1 | Rat model of cholelithiasis with human gallstones implanted in cholestasis-induced virtual gallbladder显示文摘AIM:To facilitate translational research on cholelithiasis,we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species.METHODS:Under anesthesia,16 adult rats of equal genders underwent two times of abdominal surgery.First,their common bile duct(CBD)was ligated to cause cholestasis by total biliary obstruction(TBO).On day 0,1,3,7,14,21 and 28 after TBO,magnetic resonance imaging(MRI)was conducted to monitor the dilatation of the CBD,and blood was sampled to analyze total serum bilirubin(TSB).Secondly,on day 30,the abdomen was re-opened and gallstone(s)collected from human patients were implanted in the dilated CBD asa virtual gallbladder(VGB),which was closed by suture ligation.This rat cholelithiasis model was examined by MRI,clinical observation,microcholangiography and histology.RESULTS:All rats survived two laparotomies.After ligation,the CBD was dilated to a stable size of 4 to30 mm in diameter on day 21-28,which became a VGB.The rats initially showed signs of jaundice that diminished over time,which paralleled with the evolving TSB levels from 0.6±0.3 mg/d L before ligation,through a peak of 10.9±1.9 mg/dL on day 14,until a nearly normalized value after day 28.The dilated CBD with thickened wall allowed an incision for implantation of human gallstones of 1-10 mm in diameter.The rat cholelithiasis was proven by in vivo MRI and postmortem microcholangiography and histomorphology.CONCLUSION:A rat model cholelithiasis with human gallstones has been established,which proves feasible,safe,reliable,nontoxic and cost-effective.Given the gallstones of human origin,applications of this model may be of help in translational research such as optical detection and lysis of gallstones by systemic drug administration. | Marlein Miranda Cona Yewei Liu Ting Yin Yuanbo Feng Feng Chen Stefaan Mulier Yue Li Jian Zhang Raymond Oyen Yicheng Ni | 2016 | World Journal of Methodology2016,6,2: | 7 |
| 2 | An overview of translational(radio)pharmaceutical research related to certain oncological and non-oncological applications显示文摘Translational medicine pursues the conversion of scientific discovery into human health improvement.It aims to establish strategies for diagnosis and treatment of diseases.Cancer treatment is difficult.Radiopharmaceutical research has played an importantrole in multiple disciplines,particularly in translational oncology.Based on the natural phenomenon of necrosis avidity,Onco Ci Dia has emerged as a novel generic approach for treating solid malignancies.Under this systemic dual targeting strategy,a vascular disrupting agent first selectively causes massive tumor necrosis that is followed by iodine-131 labeled-hypericin(123IHyp),a necrosis-avid compound that kills the residual cancer cells by crossfire effect of beta radiation.In this review,by emphasizing the potential clinical applicability of Onco Ci Dia,we summarize our research activities including optimization of radioiodinated hypericin Hyp preparations and recent studies on the biodistribution,dosimetry,pharmacokinetic and,chemical and radiochemical toxicities of the preparations.Myocardial infarction is a global health problem.Although cardiac scintigraphy using radioactive perfusion tracers is used in the assessment of myocardial viability,searching for diagnostic imaging agents with authentic necrosis avidity is pursued.Therefore,a comparative study on the biological profiles of the necrosis avid 123I-Hyp and the commercially available 99mTc-Sestamibi was conducted and the results are demonstrated.Cholelithiasis or gallstone disease may cause gallbladder inflammation,infection and other severe complications.While studying the mechanisms underlying the necrosis avidity of Hyp and derivatives,their naturally occurring fluorophore property was exploited for targeting cholesterol as a main component of gallstones.The usefulness of Hyp as an optical imaging agent for cholelithiasis was studied and the results are presented.Multiple uses of automatic contrast injectors may reduce costs and save resources.However,cross-contaminations with bloodborne pathogens of infectious diseases may occur.We developed a radioactive method for safety evaluation of a new replaceable patient-delivery system.By mimicking pathogens with a radiotracer,we assessed the feasibility of using the system repeatedly without septic risks.This overview is deemed to be interesting to those involvedin the related fields for translational research. | Marlein Miranda Cona Peter de Witte Alfons Verbruggen Yicheng Ni | 2013 | World Journal of Methodology2013,3,4: | 2 |
| 3 | Differential diagnosis of gallstones by using hypericin as a fluorescent optical imaging agent显示文摘AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones from cholecystectomy patients were incubated with hypericin or solvent. After 72 h, the stones were analysed for fluorescence(365 nm) and treated with 2-propanol/dimethyl sulfoxide for high performance liquid chromatography(HPLC) analysis. Rats with virtual gallbladder containing human cholesterol, mixed or pigment gallstones(VGHG) received 5 mg/kg hypericin or solvent and VGHG rats with cholesterol stones were given different hypericin doses(5-15 mg/kg). Twelve hours later, the stones were analysed at 365 nm. Biliary excretion and metabolites of hypericin were assessed in common bile duct(CBD) cannulated rats for 9 h using fluorospectrometry, HPLC and matrixassisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS).RESULTS: Homogeneous high fluorescence was seen on cholesterol stones either pre-incubated with hypericin or extracted from VGHG rats receiving hypericin. Mixed stones showed a dotted fluorescent pattern, whereas pigment and solvent-treated ones lacked fluorescence. HPLC showed 7.68, 6.65 and 0.08 × 10^(-3) M of cholesterol in extracts from cholesterol, mixed, and pigment gallstones, respectively. Hypericin accounted for 2.0, 0.5 and 0.2 × 10-6 M in that order. On cholesterol stones from VGHG rats receiving different hypericin doses, a positive correlation was observed between dose and fluorescence. In the bile from CBD-cannulated rats, fluorescence represented 20% of the injected dose with two peaks in 9 h. HPLC analysis revealed that hypericin conjugates reached 60% of the peak area. By MALDI-TOF MS, hypericinglucuronide was detected. CONCLUSION: This study proves the potential use of hypericin for differential fluorescent detection of human gallstones regarding their chemical composition. | Marlein Miranda Cona Ye-Wei Liu Antoine Hubert Ting Yin Yuan-Bo Feng Peter de Witte Etienne Waelkens Yan-Sheng Jiang Jian Zhang Stefaan Mulier Qian Xia Gang Huang Raymond Oyen Yi-Cheng Ni | 2016 | World Journal of Gastroenterology2016,22,29: | 0 |
| 4 | A single-dose toxicity study on non-radioactive iodinated hypericin for a targeted anticancer therapy in mice显示文摘目的: Hypericin (忧郁) 和它的收音机衍生物为诊断、治疗学的目的与 ischemic 心疾病和恶意在动物模型被调查了。在 radioiodinated 忧郁前(123 我忧郁或 131 我忧郁) 能被看作临床上有用的药,它的 chemotoxicity 上的精力旺盛的评估是必要的。在现在的学习,我们检验了非放射性的 127 在为 24 h 和 14 d 的正常老鼠的我忧郁。 | Jun-jie LI Marlein Miranda CONA Yuan-bo FENG Feng CHEN Guo-zhi ZHANG Xue-bin FU Uwe HIMMELREICH Raymond OYEN Alfons VERBRUGGEN Yi-cheng NI | 2012 | Acta Pharmacologica Sinica2012,33,12: | 0 |
| 5 | Separate calculation of DW-MRI in assessing therapeutic effect in liver tumors in rats显示文摘AIM:To explore whether the antitumor effect of a vascular disrupting agent(VDA)would be enhanced by combining with an antiangiogenic agent,and whether such synergistic effects can be effectively evaluated with separate calculation of diffusion weighted magnetic resonance imaging(DW-MRI).METHODS:Thirty-seven rats with implanted liver tumors were randomized into the following three groups:(1)ZD6126,a kind of VDA;(2)ZDTHA,ZD6126 in combination with an antiangiogenic,thalidomide;and(3)control.Morphological DW-MRI were performed and quantified before,4 h and 2 d after treatment.The apparent diffusion coefficient(ADC)values were calculated separately for low b values(ADC low),high b values(ADC high)and all b values(ADC all).The tissue perfusion contribution,ADC perf,was calculated as ADC low-ADC high.Imaging findings were finally verified by histopathology.RESULTS:The combination therapy with ZDTHA significantly delayed tumor growth due to synergistic effects by inducing cumulative tumor necrosis.In addition to delaying tumor growth,ZDTHA caused tumor necrosis in an additive manner,which was verified by HE staining.Although both ADC high and ADC all in the ZD6126and ZDTHA groups were significantly higher compared to those in the control group on day 2,the entire tumor ADC high of ZDTHA was even higher than that of ZD6126,but the significant difference was not observed for ADCall between ZDTHA and ZD6126.This indicated that the perfusion insensitive ADC high values calculated from high b value images performed significantly better than ADC all for the monitoring of tumor necrosis on day 2.The perfusion sensitive ADC perf derived from ADC low by excluding high b value effects could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126,compared to the ADC low at 4 h.The ADC perf could provide valuable perfusion information from DW-MRI data.CONCLUSION:The separate calculation of ADC is more useful than conventional averaged ADC in evaluating the efficacy of combination therapy with ZD6126and thalidomide for solid tumors. | Feng Chen Frederik De Keyzer Yuan-Bo Feng Marlein Miranda Cona Jie Yu Guy Marchal Raymond Oyen Yi-Cheng Ni | 2013 | World Journal of Gastroenterology2013,19,47: | 0 |
| 6 | Bifunctional staining for ex vivo determination of area at risk in rabbits with reperfused myocardial infarction显示文摘AIM: To develop a method for studying myocardial area at risk(AAR) in ischemic heart disease in correlation with cardiac magnetic resonance imaging(c MRI). METHODS: Nine rabbits were anesthetized, intubated and subjected to occlusion and reperfusion of the left circumflex coronary artery(LCx) to induce myocardial infarction(MI). ECG-triggered c MRI with delayed en-hancement was performed at 3.0 T. After euthanasia, the heart was excised with the LCx re-ligated. Bifunctional staining was performed by perfusing the aorta with a homemade red-iodized-oil(RIO) dye. The heart was then agar-embedded for ex vivo magnetic resonance imaging and sliced into 3 mm-sections. The AAR was defined by RIO-staining and digital radiography(DR). The perfusion density rate(PDR) was derived from DR for the AAR and normal myocardium. The MI was measured by in vivo delayed enhancement(i DE) and ex vivo delayed enhancement(e DE) c MRI. The AAR and MI were compared to validate the bifunctional straining for cardiac imaging research. Linear regression with Bland-Altman agreement, one way-ANOVA with Bonferroni's multiple comparison, and paired t tests were applied for statistics.RESULTS: All rabbits tolerated well the surgical procedure and subsequent c MRI sessions. The openchest occlusion and close-chest reperfusion of the LCx, double suture method and bifunctional staining were successfully applied in all animals. The percentage MI volumes globally(n = 6) and by slice(n = 25) were 36.59% ± 13.68% and 32.88% ± 12.38% on i DE, and 35.41% ± 12.25% and 32.40% ± 12.34% on e DE. There were no significant differences for MI determination with excellent linear regression correspondence(r global = 0.89; r slice = 0.9) between i DE and e DE. The percentage AAR volumes globally(n = 6) and by slice(n = 25) were 44.82% ± 15.18% and 40.04% ± 13.64% with RIO-staining, and 44.74% ± 15.98% and 40.48% ± 13.26% by DR showing high correlation in linear regression analysis(r global = 0.99; r slice = 1.0). The mean differences of the two AAR measurements on BlandAltman were almost zero, indicating RIO-staining and DR were essentially equivalent or inter-replaceable. The AAR was significantly larger than MI both globally and slice-by-slice(P < 0.01). After correction with the background and the blank heart without bifunctional staining(n = 3), the PDR for the AAR and normal myocardium was 32% ± 15% and 35.5% ± 35%, respectively,which is significantly different(P < 0.001), suggesting that blood perfusion to the AAR probably by collateral circulation was only less than 10% of that in the normal myocardium.CONCLUSION: The myocardial area at risk in ischemic heart disease could be accurately determined postmortem by this novel bifunctional staining, which may substantially contribute to translational cardiac imaging research. | Yuanbo Feng Zhan-Long Ma Feng Chen Jie Yu Marlein Miranda Cona Yi Xie Yue Li Yicheng Ni | 2013 | World Journal of Methodology2013,3,3: | 0 |