AIMTo design and synthesize compounds with insulin-sensitizing activity.

METHODSUsing association principle of drug design, ten title compounds were designed and synthesized on the basis of known compounds with insulin-sensitizing activity, and their insulin-sensitizing activity were evaluated on 3T3-L1 pre-adipocyte cells.

RESULTSOne of the synthesized compounds showed strong insulin-sensitizing activity in vitro.

CONCLUSIONThis compound may possess good sugar-lowering activity, and will be chosen for further hypoglycemic evaluation in vivo.

3T3-L1 Cells ; metabolism ; Adipocytes ; drug effects ; Animals ; Drug Design ; Hypoglycemic Agents ; chemical synthesis ; pharmacology ; Indoles ; chemical synthesis ; pharmacology ; Insulin ; pharmacology ; Mice ; Triglycerides ; metabolism

Objective To apply hydride generation atomic fluorescence spectrophotometry (HG-AFS method) in urinary arsenic detection,and to provide a better,newer and more convenient detection method for quantitative analysis of urinary arsenic.Methods According to the Guide to Develop Biological Sample Inspection Method(WS/T 68-1996) and Guide for Establishing Occupational Health Standards-part 5:Determination Methods in Biological Materials (GB/T 210.5-2008),HG-AFS method was established to detect arsenic content in urine after modification of the method for sample pretreatment,and to verify the linear range of standard curve and linearity,detection limit,precision,accuracy,stability of the sample,and to compare the experimental results of HG-AFS method with those of standard methods of WS/T 28-1996 and Determination of Arsenic in Urine by Cyanide Generation Atomic Fluorescence Method (WS/T 474-2015).Results The HG-AFS method linear range was from 0-100 μg/L,the correlation coefficient r =0.999 9,the detection limit was 0.07 μg/L,the precision was 1.96％-3.97％,and the recovery rate was 95.1％-105.0％.There was no statistical significance between HG-AFS method,the standard of WS/T 28-1996 or WS/T 474-2015 methods (t =1.539,0.353,all P ＞ 0.05).Conclusion The new method is superior to the current detection method owing to its low detection limit,high precision,good accuracy,and wide linear range.

Objective To analyze the quality control measures on urinary fluoride testing in the implementation,and to provide experience in quality control for testing activities.Method According to the Determination of Fluoride in Urine-Ion Selective Electrode Method (WS/T 89-1996),focusing on ways to complete testing all the samples in a short time,implementing internal quality control measures in the testing before,during and after the implementation by different ways as blank experiment,standard substance detection,personnel parallel experiment,paralleled detection,instrument comparison and sample test repeat,were carried out.Results The test results of blank experiment were lower than the lowest detection limit;the test results of standard material were within the scope of the standard reference,there was no significant difference between the mean value and the reference value (t =0.01,0.00,0.02,all P ＞ 0.05),|Z| values were all less than 1;the results of personnel parallel experiment,paralleled detection,instrument comparison test results and sample test repeat were not significantly different statistically (all P ＞ 0.05);the results of instrument comparison and sample test repeat were not significantly different statistically (t =0.129,0.034,all P ＞ 0.05).A total of 9 123 urine samples were tested,the geometric mean of urinery fluoride was 0.58 mg/L.Conclusion Different quality control measures should be implemented through all the testing,control personnel errors,instruments,and reagents,etc,to ensure the quality of the entire test results.

Objective To investigate the content and changes of fluoride in corn and pepper, to evaluate the effect of prevention and control measures, and to provide a basis for adjusting the prevention and control strategy. Methods In 2013, according to the different directions of east, west, south, north and center, 5 townships were selected from each coal-burning-borne endemic fluorosis areas in all 23 counties (cities, districts), and 3 villages was randomly selected from each township. Household samples of corn and dried pepper in 10 households were collected to detect fluorine content. The results of 14 counties were compared with the 2007 survey data. Results A total of 884 and 3379 samples of corn and pepper were collected, and the median fluorine content was 1.26 and 9.15 mg/kg, the range was 0.50~254.59 mg/kg and 0.50~3701.88 mg/kg, respectively. Compared with the survey data of 2007, the median fluoride content of corn of 14 counties decreased by nearly 50%, and the median amount of pepper was reduced by more than 80%. The differences were statistically significant (mg/kg:corn 1.36 vs 2.63, dried pepper 9.70 vs 55.31, Z = 3.28, 9.13, P<0.05). Conclusion The fluoride content of corn and pepper in Guizhou Province is significantly lower, but it is still relatively high in some coal-burning-borne fluorosis counties (cities, districts).

Objective:To prepare and characterize specific and discrepant mouse hybridoma antibodies on membrane of HL60 and HL60/ADR cell lines.Methods:BALB/c mice were immunized by subtractive immunization induced Cp(Cyclophosphamide).McAbs were prepared by hybridoma technique,screened and detected by FACS and LSCM.Results:51 candidates and discrepant antibodies were found,and one of them (5F6) was purified and identified.Conclusion:Combination of SI with discrepant screening method should facilitate the preparing and identifying discrepant McAbs for identifying antibodies that can distinguish the differences in proteins expressed in HL60 and HL60/ADR,which is a significative and potential method in the research and target therapy associated drug-resistance.

Ten novel compounds were designed and synthesized on the basis of compound 1, their insulin-sensitizing activities were evaluated in 3T3-L1 cells. Results showed that compound 10 exhibited strong differentiation-stimulating activity on 3T3-L1 cells model, which indicated that compound 10 may possess well insulin-sensitizing activity.
3T3-L1 Cells ; Animals ; Benzopyrans ; chemical synthesis ; pharmacology ; Drug Design ; Hypoglycemic Agents ; chemical synthesis ; pharmacology ; Insulin ; pharmacology ; Mice

Thirteen benzopyran derivatives were synthesized and their activity stimulating the differentiation of preadipocytes into adipocytes were evaluated with 3T3-L1 cells. Compound 8 was also tested for its hypoglycemic activity on db diabetes mice model. Results indicated that compounds 3, 8 and 11 exhibited strong differentiation-stimulating activity on 3T3-L1 cells model, and compound 8 can reduce the blood-sugar level of db diabetes mice dramatically.
3T3-L1 Cells ; Adipocytes ; drug effects ; Animals ; Benzopyrans ; chemical synthesis ; chemistry ; pharmacology ; Blood Glucose ; metabolism ; Cell Differentiation ; drug effects ; Diabetes Mellitus, Experimental ; blood ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Mice

OBJECTIVETo find an effective operative procedure against reflux after esophagogastric anastomosis with mucosal valve.

METHODSFour hundred and sixty-four patients with esophageal or cardiac cancer were randomly divided into three groups according to anastomosis modes. Group A underwent esophagogastric anastomosis with mucosal valve (175 cases), group B with mechanical stapler (151 cases) and group C one layer anastomosis with handcraft suture (138 cases). The gastroesophageal reflux index (GERI) was examined by isotope,and 24 h esophageal pH was also monitored. The esophageal motor function was compared among three groups.

RESULTSThe reflux rates were 0, 33.3%, and 6.7% in group A, B, C respectively. The esophageal motor function and the 24 h esophageal pH monitoring indicated that the various indexes were approaching to the normal level in group A, but the various indexes in group B and C were significantly different from the normal values (P< 0.05).

CONCLUSIONThe esophagogastric anastomosis with mucosal valve has better antireflux effect and can prevent the reflux esophagitis after esophageal or cardiac cancer eradication.

Adult ; Aged ; Anastomosis, Surgical ; methods ; Esophageal Neoplasms ; therapy ; Esophagus ; surgery ; Female ; Gastroesophageal Reflux ; prevention & control ; Heart Neoplasms ; therapy ; Humans ; Male ; Middle Aged ; Mucous Membrane ; surgery ; Stomach ; surgery

To design and synthesis a series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates with more potent anti-HBV activity, adefovir dipivoxil was used as lead compound, according to the results of enhanced oral bioavailability and antiviral activities of nucleoside L-amino acid ester prodrugs. Eleven novel L-amino acid ester prodrugs of acyclic nucleoside phosphonates were designed and synthesized, their anti-HBV activities were evaluated in HepG2 2.2.15 cells. Eight compounds exhibited antiviral activity, and compound 11 showed the most potent anti-HBV activity and highest selective index in vitro (EC50 0.0952 micromol x L(-1), SI 69523). Moreover, by analyzing the primary structure and activity relationship of these compounds, it could be suggested that L-amino acid ester strategy has significant potential in the acyclic nucleoside phosphonates prodrug design.
Amino Acids ; chemistry ; Antiviral Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Hepatitis B virus ; drug effects ; Humans ; Liver Neoplasms ; pathology ; virology ; Nucleosides ; chemical synthesis ; pharmacology ; Organophosphonates ; chemical synthesis ; pharmacology ; Prodrugs ; chemical synthesis ; pharmacology

Objective To explore the dosage and injection method of concanavalin A(Con A) for inducing Wistar rats into the acute hepatic injury model. Methods (1)According to the dosage of Con A, 42 Wistar rats were randomly divided into groups A, B, C, D, E, N, 7 rats in each group. Group N was given tail intravenous injection of normal saline as normal control group. Groups A, B, C, D, E were given intravenous injection of 4, 8, 16, 30, 40 mg/kg of Con A respectively. At the 8th hour after modeling, the levels of alanine transaminase(ALT), aspartate aminotransferase(AST), albumin(ALB), interleukin(IL)-2 , IL-10, interferon (IFN)-γ, and tumor necrosis factor(TNF)-αwere detected. And HE staining was used to observe the pathological feature of hepatic tissue. (2)According to the injection method of Con A, 21 Wistar rats were randomly divided into normal control group, intraperitoneal injection group and tail intravenous injection group, 7 rats in each group. The dosage of Con A for the rats in intraperitoneal injection group and tail intravenous injection group was 16 mg/kg. At the 8th hour after modeling, the levels of serum ALT, AST, and ALB were determined. Results The number of abnormal deaths in various dose Con A groups at the end of each experiment was 0 in groups A, B, C, and 2 in group D, and 7 in group E. A small amount of spotty necrosis, inflammatory cell infiltration, and hepatic lobule with almost integrity of structure were found in groups A, B, while obvious bridging-like necrosis was seen in groups C, D. Serum ALT, AST, and ALB levels in intraperitoneal injection group had no statistically significant difference as compared with the normal control group. Conclusion Tail intravenous injection of 16 mg/kg of Con A can be used to induce an acute immunological liver injury rat model successfully.