Objective To investigate the risk factors of gallbladder neoplastic polyps,to determine the proper surgical indications,and to understand more about the clinical characteristics of gallbladder adenoma.Methods The clinical data of 748 patients diagnosed to have polypoid lesion of gallbladder (PLG) and underwent cholecystectomy from January 1998 to December 2012 in the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively reviewed.Results Among 748 patients,340 had abdominal symptoms.Postoperative histopathology showed non-neoplastic polyps (n =659),gallbladder adenoma (n =68),gallbladder cancer (n =15) and no polyps (n =6).The mean diameters of the nonneoplastic lesions and the neoplastic polyps were (9.38 ± 3.44) mm and (14.55 ± 5.71) mm,respectively (P ＜ 0.01).The average age of the patients with non-neoplastic lesions was (44.14 ± 11.42) years and (47.39 ± 12.82) years in those with neoplastic polyps (P ＜ 0.05).The proportion of solitary PLG was 41.4％ (253/611) and 59.59％ (47/79) for the non-neoplastic lesions and the neoplastic polyps respec tively (P ＜ 0.01).The size of PLG (13.34 ± 4.18 mm vs.20.07 ± 8.19 mm,P ＜ 0.05) and the age of the patient (45.78 ± 11.66 years vs.54.13 ± 15.82 years,P ＜0.05) between the gallbladder adenoma and gallbladder cancer groups were significantly different.Gallbladder adenoma or dysplasia was identified in 66.7％ (10/15) of gal1bladder cancer specimens.Conclusions Patients with PLG and with abdominal symptoms,large size (≥ 10 mm),old age (≥50 y) and solitary polyp are indications for cholecystectomy.Gallbladder adenoma may develop to gallbladder cancer within 10 years.

Objective: To explore the comprehensive effects of folic acid (FA), riboflavin (RF) and MTHFR C677T polymorphism on genomic stability. Method: Cytokinesis-block micronucleus assay was used to detect the effects of different concentration combination of FA (20 and 200nmol/L, i.e. LF and HF) , RF (1 and 500 nmol/L, i.e. LR and HR) and MTHFR C677T polymorphism on genomic stability of 9 d cultured human lymphocytes. Results: The genetic damage was significantly higher in LFHR group regardless the genotype (P

Objective To observe the effect of the occupational therapy (OT) on people with mental disability in community of Beijing and analyze its related factors. Methods 180 mentally disabled persons from 15 disabled persons' centers (DPCs) in a district of Beijing were studied with a self-developed questionnaire. They were investigated twice with a 6-month interval, and the results were compared. Results 160 questionnaires were valid for analysis. The score of OT improved (P<0.05) in 103 (64.38%) respondents. The main factors related with the effectiveness of the OT included OT categories, age and vocational assessment. Conclusion OT is effective on people with mental disability in the DPCs, and could be improved in some aspects, such as regular vocational assessment.

Prodrug is an effective way to improve the oral absorption of the drugs which belong to Biopharmaceuticals Classification System (BCS) class III and IV. This review addresses the progress of the oral prodrugs in recent years, mainly including classical prodrug design and targeted prodrug design. Classical prodrug design is focused on modification of oil-water partition coefficient or decrease the metabolism of parent drugs. Targeted prodrug design is actively concerned with the physiological characteristics of the gastrointestinal tract to target tissues, enzymes and influx transporters. Intestinal influx transporter, the peptide transporter-targeted prodrug design is a growing field of the research of oral prodrugs recently. Challenges of prodrug strategy, design and investigation in vivo are also discussed.
Administration, Oral ; Animals ; Biological Transport ; Drug Delivery Systems ; Drug Design ; Humans ; Intestinal Absorption ; Prodrugs ; administration & dosage ; pharmacokinetics ; Solubility

Objective To investigate the effect of ambient temperature on body mass, thermogenic activity and un-coupling protein-1 ( UCP1) content of brown adipose tissue ( BAT) in tree shrews ( Tupaia belangeri) , and to provide the-oretical basis for establishing tree shrews model of obesity.Methods Forty healthy adult tree shrews with similar body mass were uesd in our experiment.The tree shrews were divided into five groups (n=8):control group (0 d), the ani-mals were maintained under 25 ±1℃ and 12L:12D ( light : dark, lights on 08:00) photoperiod; and the animals were maintained under 5 ±1℃and 12L:12D photoperiod for 7 d, 14 d, 21 d and 28 d groups, respectively.At the end of ex-periment, the changes of body mass, nonshivering thermogenesis (NST), BAT mass and uncoupling protein 1 (UCP1) con-tent were determined.Results Compared with the control group (0 d), the body mass, NST, BAT mass and UCP1 con-tent of the cold acclimation groups were improved significantly, the BAT color also obviously deepened, and after cold accli-mation for 28 d, the body mass, NST, BAT mass and UCP1 content were increased by 26.32%, 20.65, 53.85%and 43%, respectively.Apparently, the UCP1 content was significantly positively correlated with BAT mass and NST.Conclusions BAT proliferation may be induced and UCP1 expression upregulated by cold acclimation in Tupaia belangeri, therefore, en-hancing the thermogenic activity of brown adipose tissue to increase energy expenditure.We would speculate that BAT might be used as a target organ for treatment of obesity by energetic approach in the future.

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

Objective To study the impacts of variation of folate metabolic component including folic acid (FA), riboflavin (RF) and MTHFR C677T polymorphism on chromosome 8 and 17 segregation. Method RPMI1640 medium was modified with different combinations of low (LF) and high (HF) concentrations of folic acid (20, 200 nmol/L) and low (LR) and high (HR) concentrations of riboflavin (1 and 500 nmol/L). The lymphocytes with different MTFHR C677T genotype were cultured in the mentioned media for 9d. Cytokinesis was blocked by cytochalasin B and the slide was prepared as usual. The frequencies of aneuploidy of chromosomes 8 and 17 were determined by dual-color fluorescence in situ hybridization (FISH). Results The frequencies of both chromosome aneuploidy were significantly higher in low FA (LFLR+LFHR) than that in higher FA (HFLR+HFHR) (P

AIMTo establish the fundamentals for the design of scutellarin prodrug and formulation with feasible physicochemical and biopharmaceutical properties by esterifying scutellarin, an active component with poor absorption extracted from Erigeron breviscapus of Chinese medicine.

METHODSWith the method of salifying followed by esterifying, ethyl and benzyl ester of scutellarin were synthesized. Glycolamide ester of scutellarin was also synthesized with an improved method. Their structures were confirmed by MS and 1H NMR. The solubility and partition coefficient of the prodrugs were determined and their degradations were investigated in various buffers and in human plasma. The emulsion and cyclodextrin complex of glycolamide ester were prepared and the protection of the ester from degradation was compared in the intestinal tract contents. Furthermore, the degradation of glycolamide ester in the homogenates of various intestinal segments was studied. Results Three prodrugs were synthesized successfully and their structures were confirmed. Glycolamide ester of scutellarin showed better stability in the aqueous solution (t(1/2) approximately =16 d, pH 4.2) and the shortest half-life in the human serum (t(1/2) approximately =7 min). Compared with scutellarin, the solubility of glycolamide ester was increased about ten times in pH 4.0 buffer, and about thirty five times in water. Partition coefficient of the glycolamide ester increased significantly from -2.56 to 1.48. However, the ester degradation in the homogenates of intestinal mucus would be an obstacle for its absorption. The degradation rates were in the order duodenum > ileum > or = jejunum > colon. The emulsion showed a better protection of glycolamide ester from the degradation than cyclodextrin complex.

CONCLUSIONGlycolamide ester of scutellarin shows better physicochemical properties than ethyl and benzyl eater of scutellarin, but its stability in intestinal tract needs to be improved. The emulsion or / and colon-targeted delivery may be selected as one of strategies to decrease the presystemic degradation.

Animals ; Apigenin ; chemistry ; isolation & purification ; pharmacokinetics ; Emulsions ; Erigeron ; chemistry ; Esters ; Flavones ; chemical synthesis ; chemistry ; pharmacokinetics ; Glucuronates ; chemistry ; isolation & purification ; pharmacokinetics ; Glucuronides ; chemical synthesis ; chemistry ; pharmacokinetics ; Humans ; Intestinal Mucosa ; metabolism ; Intestines ; metabolism ; Male ; Plants, Medicinal ; chemistry ; Prodrugs ; chemical synthesis ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

AIMTo establish RP-HPLC method for determination of plasma scutellarin concentration and study of the pharmacokinetic behavior of scutellarin in rat after ig administration of breviscapine and its beta-cyclodextrin complex (breviscapine-beta-CD).

METHODSMobile phase composed of methanol and acetate buffer. The column was Shim-pack C18. Twelve rats randomized into 2 groups were separately given breviscapine and breviscapine-beta-CD at single dose of 10.8 mg.kg(-1). Drug in plasma was extracted and determined by HPLC. The pharmacokinetic parameters were calculated by 3P97 software.

RESULTSLinearity was obtained over the range of 10-400 ng.mL(-1). The recovery was 95.32%-98.81%. C(max) and AUC(0-12 h) of breviscapine were (154 +/- 18) ng.mL(-1) and (710 +/- 126) ng.h.mL(-1). For breviscapine-beta-CD, C(max) and AUC(0-12 h) were (328 +/- 31) ng.mL(-1) and (1,093 +/- 200) ng.h.mL(-1), respectively. There were significant differences of AUC(0-12 h) between breviscapine and breviscapine-beta-CD (P < 0.01).

CONCLUSIONThe assay method was suitable for the determination of scutellarin plasma concentration in rat. Brevescapine-beta-CD showed greater absorption compared with that of brevescapine.

Animals ; Area Under Curve ; Chromatography, High Pressure Liquid ; methods ; Drug Compounding ; Erigeron ; chemistry ; Flavonoids ; blood ; isolation & purification ; pharmacokinetics ; Male ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; beta-Cyclodextrins ; blood ; pharmacokinetics

OBJECTIVE: To explore the inhibitive effects of 1,3,8-trihydroxy-5-methoxyxanthone (TMX) on cytochrome P450s (CYP450s) in human liver microsomes. METHODS: Probe drugs were incubated with and without adding TMX to determine the changes of enzyme activities. The concentration ratio of metabolites to probe drugs was used to present enzyme activities. Concentrations of the probe drugs and their metabolites in the incubated mixture were detected by high performance liquid chromatography. RESULTS: The variations (mean, 95%CI) of the activities of CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 were 2.95 x 10(-3) (2.03 x 10(-3), 3.88 x 10(-3)), 3.14 x 10(-2) (1.87 x 10(-2), 4.42 x 10(-2)), 2.27 x 10(-3) (-1.4 x 10(-2),1.81 x 10(-2)), 7.72 x 10(-2) (-0.83 x 10(-2), 0.2374), and -0.2548 (-2.9802, 2.4707), respectively. The activities of CYP1A2 and CYP2C9 were significantly reduced in the present of TMX. CONCLUSION TMX (10 micromol/L) has significant inhibitive effect on the activities of CYP1A2 and CYP2C9, but no significant inhibitive effect on the activities of CYP2C19, CYP2E1 and CYP3A4.
Cytochrome P-450 Enzyme System ; metabolism ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; Xanthones ; pharmacology