Proteomics analysis of multiple sclerosis will provide more molecular pathology information about it.With appropriated methods of sample preparation,protein separation and identification,some proteins related to multiple sclerosis could be found and helpful for diagnosis,treatment and prophylaxis.This will improve the final diagnosis ratio of suspected cases and offer clue of drug and gene therapy exploration.Intervention of the related protein ameliorate symptom and release relapse.

OBJECTIVETo establish an HPLC method for the simultaneous determination of three major bioactive components in Jingzhi Guizhi Fuling capsules namely laetrile, paeoniflorin and paeonol.

METHODA LiChrospher C18 column (4.6 mm x 250 mm, 5 microm) was used. The chromatography was carried out with a stepwise gradient programming. The mobile phase was acetonitrile-water (containing 0.1% phosphorous acid) and the flow rate was 1.0 mL x min.

RESULTThe linear range of laetrile was 12.87-102.94 micron x mL(-1), r = 0.999 9, paeoniflorin 24.84 - 198.7 microg x mL(-1), r = 0.9999 and paeonol 12.57-100.56 microg x mL(-1), r = 0.999 9. The method is accurate with variation less than 1.5 % and recovery more than 95 %.

CONCLUSIONThe method was successfully applied to analyze three major bioactive components in Jingzhi Guizhi Fuling capsules.

Acetophenones ; analysis ; Amygdalin ; analysis ; Benzoates ; analysis ; Bridged-Ring Compounds ; analysis ; Capsules ; Chromatography, High Pressure Liquid ; methods ; Cinnamomum ; chemistry ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; isolation & purification ; Glucosides ; analysis ; Monoterpenes ; Paeonia ; chemistry ; Plants, Medicinal ; chemistry ; Polyporales ; chemistry ; Reproducibility of Results

Adolescent ; Adult ; Child ; Elliptocytosis, Hereditary ; diagnosis ; genetics ; Female ; Humans ; Male

Objective To evaluate the effect of silencing ACAT1 gene on colon cancer cells proliferation,migration,invasion and colon cancer development by using the small interference RNA (siRNA) in colon cancer cell line HT-29.Methods Acyl coenzyme A cholesterol acyltransferase 1 (ACAT1) gene was silenced in HT-29 cell lines using Hiperfect transfection reagent.The expression level of ACAT1 was detected by real time PCR.CFSE and transwell assays were used to evaluate the effect of ACAT1 gene interfering on cells proliferation,mi gration and invasion.Result ACAT1 mRNA expression decreased obviously after siRNA interference.Compared with pre-transfection,proliferation,migration and invasion of colon cancer cells have been significantly inhibited (P ＜ 0.05).Conclusion ACAT1 gene interference reduced proliferation,migration and of invasion of HT29 cells,which provide a new potential target for colon cancer treatment.

Objective To investigate the protective role of FDP to STZ induced islest apoptosis and the potential mechanisms.Methods The pancreases of the rats were treated to collect islets cells.The cells were incubated with STZ with/or FDP.Cell morphology,insulin secretion,HO-1 activity,CO content,SOD activity,GSH-px activity,iNOS activity were examined.No conetent and apoptotic percentage was detected.Results HO-1 activity and CO content of the normal control group were low.STZ induced a significant decrease of cell activity and insulin release,flow cytometry analysis showed that apoptotic percentage of islet cells remarkably increased following the addition of STZ,FDP obviously improved the islets cellular activity damaged by STZ,basic amount of insulin secretion and stimulated by high glucose were improved(P

AIMTo evaluate the hypoglycemic effect of chitosan-coated and sodium alginate-coated insulin liposomes after oral administration in mice.

METHODSInsulin-liposomes were prepared by reverse-phase evaporation. Chitosan and alginate coating was carried out by mixing liposomal suspension with chitosan and sodium alginate solutions, followed by incubation. The particle size and morphology of insulin-liposomes were determined using laser light scattering instrument and transmission electron microscopy (TEM). The entrapment efficiency was analyzed using HPLC and ultracentrifuge. The protection of insulin from peptic and tryptic digestion was studied with HPLC. The hypoglycemic effects of polysaccharide-coated insulin liposomes were investigated using the glucose oxidase method after oral administration in mice.

RESULTSThe particle size of uncoated, chitosan-coated and alginate-coated insulin-liposomes was (138 +/- 31) nm, (230 +/- 20) nm and (266 +/- 19) nm, respectively. All insulin-liposomes were of spherical or ellipsoidal shape. The entrapment efficiencies were 81.6%, 73.5% and 68.7%, respectively. Insulin was protected from tryptic digestion by chitosan-coated liposomes and protected from peptic digestion by alginate-coated liposomes. The hypoglycemic effects of insulin-liposomes, coated with 0.1% chitosan and 0.1% sodium alginate, were observed.

CONCLUSIONChitosan-coated and sodium alginate-coated liposomes were shown to reduce peptic or tryptic digestion on insulin, and enhance enteral absorption of insulin.

Administration, Oral ; Alginates ; Animals ; Blood Glucose ; metabolism ; Chitin ; analogs & derivatives ; chemistry ; Chitosan ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Glucuronic Acid ; Hexuronic Acids ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; Insulin ; administration & dosage ; pharmacology ; Liposomes ; Male ; Mice ; Particle Size ; Random Allocation ; Technology, Pharmaceutical ; methods

To study the solubilization of breviscapine with polyamidoamine (PAMAM) dendrimers and probe the solubilizing mechanism and investigate the influence of PAMAM dendrimers on the pharmacokinetics of breviscapine, the solubilization of breviscapine by PAMAM dendrimers of generations G1, G1.5, G2 and G2.5 with different concentrations were determined and compared in different pH conditions. Twelve rats randomized into 2 groups were separately orally administered breviscapine and breviscapine combining with PAMAM. Drug in plasma was extracted and determined with HPLC. In pH condition lower than 7.0, the solubilization of breviscapine by PAMAM dendrimers enhanced as the generation and concentration of PAMAM dendrimers as well as the pH increased. Its solubilizing mechanism involves an electrostatic interaction between the carboxyl group of breviscapine and the primary amines and tertiary amines of PAMAM dendrimers. The pharmacokinetics parameters Cmax and AUC0-8 h of breviscapine were (119.65 +/- 9.36) ng x mL(-1) and (370.09 +/- 63.08) ng x h x mL(-1). For breviscapine combined with PAMAM dendrimers, the Cmax and AUC0-8 h were (518.17 +/- 17.07) ng x mL(-1) and (1,219.47 +/- 201.87) ng x h x mL(-1), respectively. There were significant differences of AUC0-8 h between breviscapine and breviscapine combined with PAMAM dendrimers (P < 0.01). PAMAM dendrimers can greatly increase the solubility of breviscapine in water and can improve the oral bioavailability of breviscapine significantly.
Animals ; Area Under Curve ; Biocompatible Materials ; Biological Availability ; Dendrimers ; chemistry ; pharmacokinetics ; pharmacology ; Drug Carriers ; Erigeron ; chemistry ; Flavonoids ; chemistry ; isolation & purification ; pharmacokinetics ; Hydrogen-Ion Concentration ; Male ; Molecular Structure ; Plants, Medicinal ; chemistry ; Polyamines ; chemistry ; pharmacokinetics ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Solubility ; drug effects

OBJECTIVETo summarize the surgical outcome of patients with small cell esophageal carcinoma(SCEC).

METHODSClinical data of patients with esophageal carcinoma were retrospectively collected from March 2000 to March 2011 at the Thoracic Surgery Department of the Peking University Cancer Hospital. Data included tumor characteristics, staging, treatment, response, short-term outcome, and long-term survival.

RESULTSA total of 546 patients with esophageal carcinoma were identified, among whom there were 15 patients with SCEC(2.7%). Fourteen cases received multimodality treatment based on operation and one underwent operation alone. Four patients had preoperative chemotherapy and 10 had postoperative chemotherapy. Four patients had postoperative radiation. After excluding one case of postoperative death within 3 months, the median overall survival was 14.3 months(range, 4 to 99 months), significantly worse than those with non-SCEC(42.2 months, P<0.05).

CONCLUSIONSCEC is rare and the outcomes are poor. It should be considered as a systematic disease.

Adult ; Aged ; Carcinoma, Small Cell ; surgery ; therapy ; Combined Modality Therapy ; Esophageal Neoplasms ; surgery ; therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

AIMTo investigate the mechanisms of action of transportation of liposomes and chitosan-coated liposomes containing leuprolide across rat intestine and Caco-2 cell.

METHODSEverted-gut technique and Caco-2 cell were used to study the transport properties of free leuprolide, liposomes and chitosan-coated liposomes containing leuprolide. Caco-2 cell was used to study the effect of chitosan concentration and the order of addition on the permeation of liposomes.

RESULTSThe transport of leuprolide was passive diffusion. Probably because the entrapment by liposomes prevents the transport of leuprolide across the rat intestine and Caco-2 cell, the permeation amount of leuprolide from liposomes was lower than that of the free drug. However, liposomes protected the leuprolide from degradation. Chitosan promoted the transport of leuprolide from liposomes and there was no obvious difference in enhancement effect from the concentration of 0.1% to 0.5%. On the other hand, the incubation of chitosan with liposomes may weak the enhancement effect of chitosan.

CONCLUSIONChitosan-coated liposomes showed both protection and enhancement effect, therefore, they may promote the oral absorption of leuprolide.

Animals ; Antineoplastic Agents, Hormonal ; administration & dosage ; pharmacokinetics ; Biological Transport ; drug effects ; Caco-2 Cells ; Chitosan ; chemistry ; pharmacology ; Drug Carriers ; Drug Delivery Systems ; Humans ; Jejunum ; metabolism ; Leuprolide ; administration & dosage ; pharmacokinetics ; Liposomes ; Particle Size ; Permeability ; Rats ; Rats, Sprague-Dawley

AIMTo evaluate the characteristics, the hypoglycemic efficacy and the pharmacokinetics of the insulin-liposomes double-coated by chitosan (CH) and chitosan-EDTA conjugates (CEC).

METHODSInsulin-liposomes were prepared by reversed-phase evaporation. The protection of insulin against peptic and tryptic digestion was studied with HPLC. The hypoglycemic effects of insulin-liposomes were investigated using the glucose oxidase method after oral administration to rats. Serum insulin concentration in rats were determined by radio-immunoassay, and were assessed by Pkanalyst computer program.

RESULTSThe insulin-liposomes double-coated by CH and CEC was shown to protect insulin against digestion of pepsin, trypsin and gastrointestinal contents. In glucose tolerance test in normal rats, as compared with phosphate buffer solution control group, the insulin-liposomes coated by CH and CEC could reduce the glucose-induced peak of hyperglycemia. The reduction of the insulin-liposomes double-coated by CH and CEC was superior to that of other insulin-liposomes. When administered intragastrically to normal rats, the insulin-liposomes coated by CH and CEC could reduce glycemia measured after an overnight fast. The hypoglycemic effect the insulin-liposomes double-coated by CH and CEC was superior to that of other insulin-liposomes, and the dosage of 50 mu x kg(-1) decreased by 45.98% of initial blood glucose level at 1 h. As compared with subcutaneous injection, the relative pharmacological bioavailability was 17.02% calculated by area under the curve of glucose level versus time profile after oral administration of the insulin-liposomes double-coated by CH and CEC to rats. The serum insulin concentration-time curves were found to best fit the one-compartment open model. As compared with subcutaneous injection, the relative bioavailability was 8.91% calculated by the area under the curve of serum insulin concentration versus time profile after oral administration of the insulin-liposomes double-coated by CH and CEC to rats.

CONCLUSIONThe stability and absorption of insulin-liposomes double-coated by CH and CEC was superior to that of the insulin-liposomes coated either by CH, or by CEC respectively.

Administration, Oral ; Animals ; Biological Availability ; Blood Glucose ; metabolism ; Chitosan ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Edetic Acid ; chemistry ; Hypoglycemic Agents ; administration & dosage ; pharmacokinetics ; pharmacology ; Insulin ; administration & dosage ; pharmacokinetics ; pharmacology ; Liposomes ; Male ; Nanotechnology ; Particle Size ; Rats ; Rats, Sprague-Dawley ; Technology, Pharmaceutical ; methods