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

OBJECTIVETo observe the effects of combined treatment with sansanmycin and macrolides on Pseudomonas aeruginosa and formation of biofilm.

METHODSMicro-dilution method was used to determine the minimal inhibitory concentrations (MICs) of sansanmycin, gentamycin, carbenicillin, polymyxin B, roxithromycin, piperacillin, and tazobactam. PA1 and PA27853 biofilms were observed under optical microscope after staining and under SEM after treatment with sansanmycin at different dosages and combined treatment with sansanmycin and roxithromycin. Viable bacteria in PA1 and PA27853 biofilms were counted after treatment with sansanmycin at different dosages or combined treatment with sansanmycin and roxithromycin.

RESULTSThe MIC of sansanmycin was lower than that of gentamycin and polymyxin B, but was higher than that of carbenicillin. Roxithromycin enhanced the penetration of sansanmycin to PA1 and PA27853 strains through biofilms. PA1 and PA27853 biofilms were gradually cleared with the increased dosages of sansanmycin or with the combined sansanmycin and roxithromycin.

CONCLUSIONSub-MIC levels of roxithromycin and sansanmycin substantially inhibit the generation of biofilms and proliferation of bacteria. Therefore, combined antibiotics can be used in treatment of intractable bacterial infection.

Animals ; Anti-Bacterial Agents ; administration & dosage ; pharmacology ; Bacterial Adhesion ; drug effects ; Biofilms ; growth & development ; Cercopithecus aethiops ; Drug Therapy, Combination ; Macrolides ; administration & dosage ; pharmacology ; Microbial Sensitivity Tests ; Oligopeptides ; administration & dosage ; pharmacology ; Pseudomonas aeruginosa ; drug effects ; physiology ; ultrastructure ; Uridine ; administration & dosage ; analogs & derivatives ; pharmacology ; Vero Cells

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

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

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

Adult ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; diagnosis ; Humans ; Male ; Middle Aged ; Prognosis

Objective To investigate the efficacy and safety of rivaroxa-ban in the prevention of deep vein thrombosis in patients with hip arthro-plasty.Methods Ninety-eight patients with hip arthroplasty were re-cruited in our hospital.The included 98 cases were randomized divided into rivaroxaban group ( n=46 ) with rivaroxaban 10 mg · d -1 orally with 5-week and low molecular heparin ( LMH) group with LMH 4100 U with 2-week.The risk of deep vein thrombosis between the two groups was recorded within the flowing 6 months.Results With a follow-up peri-od of 6 months, the incidence of deep vein thrombosis were 2.3%(1/44) and 14.6%(7/58) in the rivaroxaban group and LMH group re-spectively , which indicated the incidence was much lower in rivaroxaban group ( P<0.05 ).But the platelet count , coagulation function , drainage volume and subcutaneous ecchymosis were not different between the two groups ( P>0.05 ).Conclusion Rivaroxaban can significant decrease the risk of deep vein thrombosis in patients with hip arthroplasty without increasing the side effects.

AIM To investigate the effect of Wendan Decoction on nerve injury in a mouse model of sleep disorders and its mechanism.METHODS A mouse model of insomnia was established by the modified multiple platform sleep deprivation method.After successful modeling,the mice were randomly divided into the model group,the estazolam tablet group(0.15 mg/kg)and the low-dose and high-dose Wendan Decoction groups(12.5,50 g/kg),with 6 mice in each group,in contrast to the 6 mice of the control group.After 7 days of drug intervention,the mice had their changes of cerebral cortex,hippocampal CA1 area and hypothalamus observed by HE staining;their neuronal damage observed by Nissl staining;their levels of neurofilament light chain(NEFL),neuron-specific enolase(NSE),S100 calcium-binding protein B(S100B),tumor necrosis factor(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1β)in brain tissue and serum detected by ELISA;their cerebral expression of glial fibrillary acidic protein(GFAP)detected by immunohistochemical method;and their cerebral expressions of GFAP,phosphorylated IκB kinase β(p-IKKβ)and phosphorylated nuclear transcription factor-κB(p-NF-κB)detected by Western blot.RESULTS Compared with the model group,the high-dose Wendan Decoction group displayed increased number of neurons,complete and neatly arranged structure;decreased number of neurons with nuclear shrinkage and deformation;increased Nissl bodies,decreased levels of NEFL,NSE,S100B,TNF-α,IL-6 and IL-1β in serum and brain tissue(P＜0.01);decreased cerebral expression of GFAP(P＜0.01);and decreased phosphorylation levels of cerebral p-IKKβ and p-NF-κB(P＜0.01).CONCLUSION Wendan Decoction can reduce the nerve damage and the expression of proinflammatory mediator in sleep disorders mice,and the mechanism may be related to the inhibited activation of IKKβ/NF-κB pathway.

OBJECTIVETo improve the recognition of Fechtner syndrome.

METHODSThe clinical and laboratory data and family survey of a patient with Fechtner's syndrom was reported.

RESULTS AND CONCLUSIONGiant platelets, thrombocytopenia and characteristic granulocyte inclusion bodies (Döhle-like bodies) were found in both peripheral blood and bone marrow smears of the patient. Clinically the patient had renal damage, nervous deafness, and vitreous lesions. There was a family genetic tendency on family survey the diagnosis of Fechtner syndrome is established.

Hearing Loss, Sensorineural ; etiology ; genetics ; Humans ; Male ; Middle Aged ; Molecular Motor Proteins ; genetics ; Mutation ; Myosin Heavy Chains ; genetics ; Nephritis, Hereditary ; etiology ; genetics ; Thrombocytopenia ; etiology ; genetics

Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to have a radiosensitization effect on tumors. However, its effects on human glioma and the specific molecular mechanisms of these effects remain unknown. In this study, we demonstrated that Tet has a radiosensitization effect on human glioma cells. It has been hypothesized that Tet has a radiosensitization effect on glioma cells by affecting the glioma cell cycle and DNA repair mechanism and that ERK mediates these activities. Therefore, we conducted detailed analyses of the effects of Tet on the cell cycle by performing flow cytometric analysis and on DNA repair by detecting the expression of phosphorylated H2AX by immunofluorescence. We used western blot analysis to investigate the role of ERK in the effect of Tet on the cell cycle and DNA repair. The results revealed that Tet exerts its radiosensitization effect on glioma cells by inhibiting proliferation and decreasing the expression of phosphorylated ERK and its downstream proteins. In summary, our data indicate that ERK is involved in Tet-induced radiosensitization of glioma cells via inhibition of glioma cell proliferation or of the cell cycle at G0/G1 phase.
Blotting, Western ; Cell Cycle ; Cell Proliferation ; DNA Repair ; Fluorescent Antibody Technique ; Glioma* ; Humans* ; Phosphorylation*