BACKGROUND: Nestin is a specific antigen of neural stem cells which widely expressed in lesion of nervous system and brain regeneration.Thus,nestin expression is commonly used to assess whether lesion or damage of the nervous system can promote neural regeneration.OBJECTIVE: To investigate the effects of erythropoietin(EPO)on nestin expression in neural stem cells after hypoxia-ischemia brain damage(HIBD)in neonatal rats from the angles of neural regeneration and activation of neural stem cells.METHODS: HIBD model was established by ligation of the right common carotid artery along with 2-hour 8% hypoxia exposure in neonatal rats.The control group was not subjected to hypoxia-ischemia,and the right common carotid artery was dissociated.The treatment group received an intraperitoneal injection of recombinant human erythropoietin(rh-Epo,5 000 IU/kg)once a day for three days after hypoxia/ischemia,while the two other groups intraperitoneally received normal saline at the same time.In each group,rats were randomly executed immediately,at 4,7,14 days after operation(n = 8).The nestin expression in hippocampal dentate gyrus region was examined by immunohistochemical staining and image quantitative analysis respectively.RESULTS AND CONCLUSION: The number of nestin-positive cells was significantly increased in HIBD group compared to control group at all time points(P < 0.05),and it was also significantly increased in treatment group than the other two groups at all time points(P < 0.05).The numbers of nestin-positive cells in hippocampal dentate gyrus region were significantly increased,and peaked on day 7 after operation in the three groups.The results showed that exogenous rh-Epo could enhance the expression of nestin in hippocampal dentate gyrus region of neonatal rats with HIBD,and promote the proliferation of neural stem cells,rh-Epo plays an important role in the regeneration and repair of neurocytes damaged by hypoxia-ischemia.

Objective To investigate the relationship between the expression of DNA methyltransferases(DNMT)and clinical prognosis in children with acute leukemia(AL).Methods The mRNA expressions of DNMT1,DNMT3A,DNMT3B,p15,mdrl were measured in 56 AL children and 20 normal controls by semi-quantitative reverse transcriptionpolymerse chain reaction.Results In 56 cases of children with AL,the positive rate of DNMT1 was 73.2%(41/56);the positive rate of DNMT3A was 67.9%(38 /56);the positive rate of DNMT3B was 64.3%(36/56).Thirty-one cases showed positive expressions of the 3 DNMT simultaneously,4 cases with negative expressionss imultaneously,21 cases with at least 1 positive expression of the DNMT,positive rate of p15 was 19.6%(11/56);positive rate of mdrl was 28.6%(16/56),all 3 simultaneous expressions of the 3 DNMT in AL children were significantly higher than those in normal controls(P

OBJECTIVE:To establish a method for the determination of dasatinib concentration in human plasma and study the bioequivalence of 2 kinds of tablets. METHODS:In a randomized two-way crossover study,24 healthy male volunteers were divid-ed into two groups,and were administered respectively with test and reference preparations 100 mg under fasting and fed condi-tions. The plasma concentration of dasatinib was determined by LC-MS/MS. Using imatinib mesylate as internal standard,the deter-mination was performed on Welchrom C18 column with mobile phase consisted of acetonitrile-0.1% formic acid(70∶30,V/V). Posi-tive ion scanning was conducted under MRM mode,ESI,and ion pair for quantitative analysis were m/z 488.5→401.2 (dasatinib) and m/z 494.6→394.2(internal standard). DAS 3.2.8 software was used for data processing and variance analysis was adopted to in-vestigate the bioequivalence of 2 kinds of tablets. RESULTS:The linear rang of dasatinib was 1-300 ng/ml. The pharmacokinetic pa-rameters of test and reference preparations under fasting conditions were as follows:cmax were (165.599 ± 67.592) and (164.533 ± 77.960)ng/ml;tmax were(1.145±0.504)and(1.080±0.467)h;t1/2 were(5.080±2.262)and(3.771±1.596)h;AUC0-36 h were (550.487 ± 256.494) and (585.986 ± 324.885) ng·h/ml. The pharmacokinetic parameters of test and reference preparations under fed conditions were as follows:cmax were(163.058±47.533)and(165.440±53.012)ng/ml;tmax were(1.630±1.066)and(1.576± 0.530)h;t1/2 were(4.720±2.677)and(4.311±2.610)h;AUC0-36 h were(568.036±192.521)and(601.100±216.855)ng·h/ml. Relative bioavailability of AUC0-36 h under fasting and fed conditions were(100.2±7.5)% and(99.2±3.8)%. Analysis of variance showed there were no significant difference in the pharmacokinetic parameters of between 2 preparations and cyde(P>0.05),there was statistical significance among subjects(P<0.05). CONCLUSIONS:LC-MS/MS method can determine the concentration of da-satinib in human plasma rapidly;and the two preparations are bioequivalent.

Urokinase plasminogen activator receptor (uPAR) is a membrane protein which is attached to the cellular external membrane. The uPAR expression can be observed both in tumor cells and in tumor-associated stromal cells. Thus, in the present study, the human amino-terminal fragment (hATF), as a targeting element to uPAR, is used to conjugate to the surface of superparamagnetic iron nanoparticle (SPIO). Flowcytometry was used to examine the uPAR expression in different tumor cell lines. The specificity of hATF-SPIO was verified by Prussian blue stain and cell phantom test. The imaging properties of hATF-SPIO were confirmed in vivo magnetic resonance imaging (MRI) of uPAR-elevated colon tumor. Finally, the distribution of hATF-SPIO in tumor tissue was confirmed by pathological staining. Results showed that the three cells in which we screened, presented different expression characteristics, i. e., Hela cells strongly expressed uPAR, HT29 cells moderately expressed uPAR, but Lovo cells didn't express uPAR. In vitro, after incubating with Hela cells, hATF-SPIO could specifically combined to and be subsequently internalized by uPAR positive cells, which could be observed via Prussian blue staining. Meanwhile T2WI signal intensity of Hela cells, after incubation with targeted probe, significantly decreased, and otherwise no obvious changes in Lovo cells both by Prussian blue staining and MRI scans. In vivo, hATF-SPIO could be systematically delivered to HT29 xenograft and accumulated in the tumor tissue which was confirmed by Prussian Blue stain compared to Lovo xenografts. Twenty-four hours after injection of targeting probe, the signal intensity of HT29 xenografts was lower than Lovo ones which was statistically significant. This targeting nanoparticles enabled not only in vitro specifically combining to uPAR positive cells but also in vivo imaging of uPAR moderately elevated colon cancer lesions.
Cell Line, Tumor ; Colonic Neoplasms ; diagnosis ; Ferric Compounds ; Humans ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; chemistry ; Molecular Imaging ; methods ; Receptors, Urokinase Plasminogen Activator ; chemistry ; Staining and Labeling

Amphotericin B ; administration & dosage ; therapeutic use ; Antifungal Agents ; administration & dosage ; therapeutic use ; Biomarkers ; blood ; Child ; Cough ; diagnosis ; drug therapy ; etiology ; Cryptococcosis ; Fever ; diagnosis ; drug therapy ; etiology ; Fluconazole ; administration & dosage ; therapeutic use ; Humans ; Lung ; diagnostic imaging ; pathology ; Lung Diseases, Fungal ; complications ; diagnosis ; drug therapy ; Male ; Radiography, Thoracic ; Tomography, X-Ray Computed

Objective To find out the status of prevention and control of iodine deficiency disorders and evaluate the iodine nutritional status of Jinan residents,to explore appropriate iodine level in drinking water,and to provide a scientific basis for adjustment of intervention strategies.MethodsAccording to the Monitoring Program of the National Iodine Deficiency Disorders (Trial),qualified iodized salt consumption rate,drinking water iodine content and urinary iodine levels of women of childbearing age were determined in iodine deficiency areas from 2003 to 2010.Salt iodine was detected by direct titrimetry,urinary iodine by As-Ce catalytic spectrophotometric assay and iodine in drinking water by cerous sulfate catalytic spectrophotometric method.Results Intake rate of qualified iodized salt was up to 90％ and above from 2003 to 2010,median water iodine was 13.65 μg/L in the 10 counties(cities,districts),of which less than 100 μg/L accounted for 79.82％(4560/5713 ) and ＞ 150 μg/L accounted for 12.73％(727/5713).With the increase of water iodine(0 ～ ＜ 10,10 ～ ＜ 50,50 ～ ＜ 100,100 ～ ＜ 150,150 ～ ＜ 300 and ≥300 μg/L),urinary iodine levels of women of childbearing age increased successively(median 156.56,175.81,267.04,349.00,524.22,583.20 μg/L,respectively,x2 =121.20,P ＜ 0.05),while the ratio of urinary iodine ＜ 100 μg/L was significantly lower.The ratio of urinary iodine between 100 and 300 μg/L was decreased gradually,but the ratio of great than 300 μg/L was gradually increased.ConclusionsIodine deficiency areas in Jinan have reached the standard of elimination of iodine deficiency disorders.We should insist to carry out our measures to suit local conditions,classified guidances and scientific principals of iodine supplementation.

Adolescent ; Bile Reflux ; etiology ; Child ; Child, Preschool ; Female ; Gastritis ; etiology ; Gastroscopy ; Helicobacter Infections ; complications ; diagnosis ; Helicobacter pylori ; Humans ; Male

Affinity chromatography is a chromatographic method for separating molecules using the binding characteristics of the stationary phase with potential drug molecules. This method can be performed as a high throughput screening method and a chromatographic separation method to screen a variety of active drugs. This paper summarizes the history of affinity chromatography, screening technology of affinity chromatography, and application of affinity chromatography in screening bio-active compounds in herbal medicines, and then discusses its application prospects, in order to broaden applications of the affinity chromatography in drug screening.
Animals ; Chromatography, Affinity ; methods ; trends ; Drug Evaluation, Preclinical ; methods ; trends ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Humans ; Plants, Medicinal ; chemistry

AIM: To determine the concentration of escitalopram in human plasma by HPLC-MS/MS and investigate the pharmacokinetics of escitalopram. METH-ODS: The method involved protein precipitation with methanol. The chromatographic separation was achieved within 6.0 min by using methanol-water with 15 mmol·L-1 ammonium acetate-formic acid (72:28:O.1, v/v/v) as mobile phase and a Lichrospher CN 150 mm×4.6 mm analytical column. The analytes were detected using an electrospray ionization tandem mass spectrometry in SRM mode. Detection of the ions was performed by monitoring the transitions of m/z 325.0 to 234.0 for escitalopram and m/z 409.1 to 238.1 for amlodipine (intemal standard), respectively. RESULTS:The standard curve was linear ( r = 0. 999) over the concentration range of 0.20 - 50.00 ng· ml- 1. Accuracy and precision were below the acceptance limits of 15%. The recoveries of escitalopram ranged from 96.0% to 103.6%. The lower limit of quantification for escitalopram was 0.20 ng· ml-1 using 200 μl plasma sample.The pharmacokinetic parameters of escitalopram after a single oral dosing of escitalopram oxalate tablet (10 rog)to ten healthy male volunteers were achieved. The Cmax, Tmax, AUC0-t, AUC0-∞, t1/2 and Ke of escitalopram were 9.21±2.10 ng·ml-1 , 3.75±1.04 h, 514.6±152.3 ng·h·ml-1 ,540.5±162.3 ng·h·ml-1 , 34.06±7.71 h and 0.021±0.004 h-1,respectively. CONCLUSION:The determination of concentration of escitalopram in human plasma by HPLC-MS/MS method was repid, sensitive and reliable. It can be used for clinical pharmacokinetic study of escitalopram.

Objective To study the association between the plasma homocysteine level and coronary artery disease(CAD), and the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism, the methionine synthase (MS) A2756G polymorphism and their associations to the plasma homocysteine level and CAD in the elderly . Methods One hundred and twenty-nine elderly patients with CAD documented by coronary angiogram and 48 elderly patients with normal coronary angiographic results were included in this study. Plasma homocysteine level were measured by fluorescence polarization immunoassay (FPIA) method and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to analyse the MTHFR A1298C and MS A2756G genotypes. Results The plasma homocysteine level was significantly higher in CAD group than that in the control group〔(16.2?8.6) ?mol/L vs (12.7?5.0) ?mol/L,P0.05);the prevalence of MTHFR 1298CC homozygous in the CAD patients was significantly less than that in the control group (3.1% vs 14.6%, P