Objective To prepare a thrombus-targeted ultrasonic contrast agent and to investigate its targeted ability to fresh blood clots. Methods We first synthesized FITC-KGDS-Palm compound, and then prepared thrombus-targeted microbubbles using "ultrasound & high speed shearing method".Fluorescence labeling thrombus-specific peptides and KGDS,directed at the activated glycoprotein(GP)Ⅱb/Ⅲa receptor of platelets were attached to the surface of lipid microbubbles. The concentration and size of TUCA were measured by Malvern Zeta Sizer Nano-ZS590 and Coulter counter.Immunofluorescence was applied to confirm the conjugation.The conjunct ratio was assessed by flow cytometer (FCM).Results The KGDS-TUCA was straw yellow turbid liquor,and the concentration was 1.5×10~9/mL,and the average size was 1.5 μm. The targeted microbubbles conjugated with the thrombus-specific peptides showed bright green rings by fluorescence microscope.FCM demonstrated that the wavelength of shell of KGDS-TUCA changed greatly,and the conjunct ratio was 90.04%.In vitro study showed KGDS-TUCA remained stable for 48 h at 4 ℃ and target-attached to blood clots and showed good stability.Conclusion The ultrasound & high speed shearing method to prepare TUCA is easy and in favor of purification.KGDS-TUCA has high specific biological activity.The conjunct ratio and stability of KGDS-TUCA are excellent.

10.3969/j.issn.1007-3969.2013.04.00X

Animals ; Bridged Bicyclo Compounds ; metabolism ; Cytochrome P-450 CYP3A ; biosynthesis ; genetics ; Drug Design ; Drug Interactions ; Enzyme Induction ; Humans ; Lithocholic Acid ; metabolism ; Phloroglucinol ; analogs & derivatives ; metabolism ; Receptors, Cytoplasmic and Nuclear ; genetics ; metabolism ; physiology ; Receptors, Steroid ; genetics ; physiology ; Signal Transduction ; Terpenes ; metabolism ; Transcription Factors ; genetics ; metabolism

Objective To observe the therapeutic effect of brucine nanoparticles on hepatocellular carcinoma.Methods Brucine nanoparticles with block copolymer of carboxylation polyethylene glycol and polylactic acid were manufactured by ultraphonic emulsification.The effect brucine nanoparticles on growth of SMMC-7721 cell line was observed in vitro.The protein and mRNA levels of Fas were measured with Western blotting and FQ-PCR respectively after the brucine nanoparticles were added into cell culture fluid for 72 hours.Results The mean diameter,the carried drug rate and the entrapment rate of brucine nanopaticles was 146±96 nm,4.2％ and 67％,respectively.The growth inhibition of liver cancer cells was enhanced significantly with the increasing drug dose.The IC50 of growth inhibition of 5-FU,brucine and brucine nanoparticles was 16.7 μg/ml,90.3 μg/ml and 164.9 μtg/ml,respectively.There was significant difference among them (P＜0.05).The protein and mRNA expression of Fas in brucine nanoparticles treated SMMC-7721 cells increased significantly compared with that in blank control group(P＜0.05).Conclusion Brucine nanoparticles may potentially be a novel therapeutic drug for hepatocellular carcinoma.

BackgroundIron-containing foreign body trapped in the eyeball wall without affecting the opticus occurs occasionally in clinic. Operation always is performed in an attempt to avoid the deposition of rust in different tissues of the eye-balls. However,a few animal experimental studies showed that a small foreign body does not affect the retina and opticus in the period of three months. The question of whether surgery needs to be carried out is worth discussion. ObjectiveThe aim of this study was to evaluate the influence of posterior intrascleral iron foreign body on the rabbit retina and opticus. MethodsTwelve healthy adult Japan flap-eared white rabbits were randomly divided into two groups. Medium carbon iron with rust or without rust( size of 2. 0 mm × 1. 0 mm×0. 2 mm) were implanted into the posterior sclera of the left eye to create the animal model with iron foreign body in the eyeball wall. The cornea, anterior chamber, crystalline lens, vitreous and fundus of the rabbits were observed under a slit lamp microscope 1weekbeforeoperationand 1week, 2weeks, 1monthand 3months after operation.Flash electroretinogram(F-ERG) and flash visual evoked potential (F-VEP) were recorded at the time points mentioned above. All the rabbits were sacrificed and the eye balls were extracted at the end of the experiment, and the position of the iron foreign body was determined. The histopathological examinations of the retina and opticus were performed under the light microscope. This experiment complied with the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission. ResultsThere were no statistical differences for the a-wave amplitude of F-ERG among different time points( F =1. 885,P =0. 129 ) and different treatment groups ( F =1. 188, P =0. 340 ), as with the ERG b-wave amplitude ( time: F =2. 73, P =0. 064 ; group : F =1. 114, P =0. 367). The differences in the latencies of F-VEP N1-wave were insignificant among the different time points( F =1. 605, P =0. 263 ) as well as various groups ( F=1. 556, P =0.314 ), and those of F-VEP P1 -wave were not evidently changed ( time: F =2. 329, P =0. 092 ; group : F =2. 186, P =0. 103 ). No correlations were seen between the time factor and grouping factor ( P ＞ 0. 05 ). There was no apparent siderosis bulbi change during the follow-up duration. No morphological abnormality in the retina and optical nerve was found under the light microscope. At the end of the experiment,intrascleral iron foreign body was wrapped by surrounding tissue in a stable condition. Conclusions The small posterior intrascleral iron foreign body, whether it is oxidized or not, does not produce distinctive functional or pathological damage on retina and opticus in the short term.

Objective To systematically review the effectiveness and safety of pantoprazole ( PAN ) vs. ranitidine (RAN) for patients with gastroesophageal reflux disease (GERD). Methods PubMed,Medline,EMbase,The Cochrane Library and three Chinese literature databases (CNKI,VIP and Wan fang) were retrieveed.Randomized controlled trials (RCTs) which compared the clinical outcomes of PAN group vs. RAN group for GERD were included. Two reviewers independently screened literatures in accordance with the inclusion and exclusion criteria, extracted the data and assessed the methodological quality of included studies.Then,meta-analysis was performed using RevMan 5.2 software. Results A total of 8 RCTs involving 1 590 patients were included.The results of meta-analysis showed that the PAN group was significantly superior to RAN group in terms of the healing rates and the relief rates of chief symptom for GERD of gradeⅠ-Ⅲ. While there was no significant difference in the incidence of adverse events between the two groups [GradeⅠ,RR=1.17,95%CI (0.80,1.70),P=0.43;GradeⅡorⅢ, RR=0.76,95%CI (0.43,1.36);P=0.36]. Conclusion Current evidence indicates that,pantoprazole is more effective than ranitidine for GERD of grade Ⅰ-Ⅲ,but both treatments are safe and well tolerated.

OBJECTIVETo study the effects of Si-Wu-Tang on serum protein of blood deficient mice b y proteomicstechnique and study the enriching and regulating blood mechanism of Si-Wu-Tang on mocular level.

METHODThe blood deficient mice was induced by using a single dose of 3.5 Gy radiation from a 60Cogamma source, and high resolution two-dimensional polyacryamide gel electrophoresis (2-DE), computer-assisted image analysis, and mass spectrometry were used to detect regulated protein by Si-Wu-Tang.

RESULT12 lower and 4 higher protein in sera could be recovered by Si-Wu-Tang, 4 protein might be DNA-dependent protein kinase catalytic subunit, Dystrophin, KIF13A, dystonin. They play a part in DNA double-stranded break repair, recombination and modulation of transcription, transportation of mannose-6-phosphate receptor, etc.

CONCLUSIONSi-Wu-Tang can regulate serum protein in blood deficient mice, resulting in improving hematopoiesis and lessening irradiated injury.

Animals ; Autoantigens ; blood ; Carrier Proteins ; Cytoskeletal Proteins ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Dystonin ; Dystrophin ; blood ; Female ; Kinesin ; blood ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins ; Non-Fibrillar Collagens ; blood ; Plants, Medicinal ; chemistry ; Radiation Injuries, Experimental ; blood ; Radiation-Protective Agents ; pharmacology ; Whole-Body Irradiation

The study is designed to synthesize nano-carrier Tyr-RGD (cyclo-[Arg-Gly-Asp-d-Tyr-Lys]) and poly(ethylene glycol) modified polyethylenimine (Tyr-RGD-PEG-PEI) targeting vascular endothelial cells, then analyze its nanoparticle properties and the characteristics of drug carrying and targeting properties in vivo / in vitro tumor. The nano-carrier Tyr-RGD-PEG-PEI was synthesized with the method of chemical synthesis and the properties of this nanoparticle and drug carrying characteristics were identified. Its effect of targeting vascular endothelial cells in vitro was studied with the method of competitive binding assay. The fluorescent labeled nano-drug was injected into tumor-bearing nude mice to observe its tumor-targeting. The mean size of nano-carrier Tyr-RGD-PEG-PE was about 145 nm, good in encapsulation efficiency of siRNA. After incubation in plasma for half an hour, only about 3 percent of siRNA out. It was confirmed that it was a single spot with TLC analysis, the R(f) value was 0.65. Receptor competition experiments showed that the nano could effectively compete with RGD in binding the receptors on endothelial cells. Tumor-bearing nude mice experiments showed that when containing a fluorescent-labeled siRNA of Tyr-RGD-PEG-PEI nano-drug was injected into mice, after 24 hours this nano-drug mainly distributed within the tumor tissue. However, nano-drug without Tyr-RGD appeared in tumor tissue as well as other organs such as livers, lungs, etc. The Tyr-RGD-targeted gene vector Tyr-RGD-PEG-PEI synthesized in this study has good nanoparticle properties and high efficiency of gene-drug encapsulation. Study of nude mice shows that the ability of its tumor-targeting is significantly better than nano-drug without Tyr-RGD.
Animals ; Endothelial Cells ; metabolism ; Gene Transfer Techniques ; Genetic Vectors ; Humans ; Integrins ; biosynthesis ; Mice ; Mice, Nude ; Nanoparticles ; Oligopeptides ; chemical synthesis ; pharmacology ; RNA, Small Interfering

Esophagogastric Junction/surgery* ; Gastrectomy/methods* ; Humans ; Laparoscopy/methods* ; Retrospective Studies ; Stomach Neoplasms/surgery*

BACKGROUNDThe underlying mechanism of early neurobiological impairment after subarachnoid hemorrhage (SAH) is not well understood, but the system of reactive oxygen superoxide (ROS) might be involved. Edaravone (MCI-186), a potent free radical scavenger that prevents apoptosis of neurons, was thus used in this study to see its possible therapeutic effect in early brain injury due to SAH in a rat model.

METHODSOne hundred and twenty male Sprague-Dawley rats were randomly assigned to four groups: group 1, control rats receiving sham operation only; group 2, rats with SAH treated by saline; group 3, rats with SAH treated with 1 mg/kg MCI-186 injected intraperitoneally; and group 4, rats with SAH treated with 3 mg/kg MCI-186. Treated with either saline or MCI-186 twice daily for two consecutive days after SAH, the rats were sacrificed for measurements of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and histological analysis of caspase-3 protein by Western blotting and immunohistochemical staining. In addition, mortality and neurological scores were statistically analyzed by the chi-square test and Dunn's procedure respectively for each group. One-way analysis of variance followed by the Tukey's procedure was also used in data analysis.

RESULTSThe rats in group 2 that received saline only showed neurological impairment as well as elevated mortality, and were found to have significantly increased levels of MDA and caspase-3, but reduced SOD activities in brain tissues (P < 0.05). When treated with MCI-186 at two different dosages, the rats in groups 3 and 4 had markedly decreased levels of MDA and caspase-3 but increased SOD activities in the brain tissue (P < 0.05), along with improved scores of neurological evaluation (P < 0.05).

CONCLUSIONSThis study sheds some lights on the therapy of SAH-induced early brain injury by providing the promising data indicating that MCI-186, a radical scavenger, can efficiently diminish apoptosis of neurons and thus prevent the function loss of the brain in rats with SAH.

Animals ; Antipyrine ; analogs & derivatives ; therapeutic use ; Blotting, Western ; Brain Injuries ; drug therapy ; etiology ; Immunohistochemistry ; Male ; Malondialdehyde ; metabolism ; Neuroprotective Agents ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; physiopathology ; Superoxide Dismutase ; metabolism