A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.
Administration, Oral ; Area Under Curve ; Asian Continental Ancestry Group ; Chromatography, Liquid ; Cyclohexanols ; blood ; pharmacokinetics ; Delayed-Action Preparations ; Desvenlafaxine Succinate ; Dose-Response Relationship, Drug ; Healthy Volunteers ; Humans ; Male ; Plasma ; chemistry ; Stereoisomerism ; Tablets ; Tandem Mass Spectrometry

Objective To study the characteristics of event-related potentials P300 in patients with anxiety disorder(AD). Methods P300 tests were carried out in 30 patients with AD and 30 healthy adult controls. ResultsPatients with AD had significantly delayed P3 latency ([326?16] ms vs [339?19]ms, P

Syl948 is a synthesized selective S1P1 agonist with novel structure. HTRF-IP1 test indicated that Syl948-P, the active form of Syl948 in vitro, has strong activity against S1P1 (EC50: 83 +/- 16 nmol x L(-1)), but its effect on S1P3 was very weak (EC50: 1 026 +/- 90 nmol x L(-1)). In SD rats, oral administration of Syl948 10 mg x kg(-1) significantly decreased the peripheral blood lymphocytes (PBL), with the maximal PBL inhibition rate of 63%, which was as similar as equal dose of fingolimod (FTY720). Oral administration of Syl948 10 mg x kg(-1) had no effect on heart rate of SD rats, which was better than FTY720. Daily oral administration with Syl948 (2 or 4 mg x kg(-1)) significantly prolonged the survival time of the allografts of skin slice on mice. In summary, the above results demonstrated that Syl948 has great selectivity in vitro and good activity in vivo, which indicated its potential use as an anti-rejection drug in skin transplantation.
Animals ; Fingolimod Hydrochloride ; Graft Survival ; drug effects ; Immunosuppressive Agents ; pharmacology ; Lymphocytes ; drug effects ; Mice ; Propylene Glycols ; pharmacology ; Rats ; Receptors, Lysosphingolipid ; agonists ; Skin Transplantation ; Sphingosine ; analogs & derivatives ; pharmacology ; Transplantation, Homologous

Since 1980s, the treatment of acute myocardial infarction (AMI) has entered the era of revascularization of infarction-related artery. There is still shortness of ideal strategy in modern medicine for comprehensive intervention aiming at the complex pathological links such as myocardial no-reflow, slow-reflow and reperfusion injury after revascularization. Therefore, combining traditional Chinese medicine with modern medicine, selecting effective drugs or prescriptions, and exploring their effective ingredients and portions of them as well as the mechanisms of the combinations in promoting myocardial capillary angiogenesis and cardiac muscle cell differentiation, and regulating the repairing process of inflammatory reaction will provide new intervening target directions and comprehensive intervening patterns for the prevention and treatment of AMI.
Angioplasty, Balloon, Coronary ; Combined Modality Therapy ; Drug Therapy ; methods ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Myocardial Infarction ; therapy ; Phytotherapy ; methods

OBJECTIVETo observe the effect of Tribuli saponins (TS) on left ventricular remodeling after acute myocardial infarction (AMI) in rats with hyperlipemia.

METHODSA composite model of myocardial infarction and hyperlipemia was established and treated with TS to observe its effect on cardiac structure and function by echocardiography.

RESULTS(1) Cardiac function: As compared with the model group, the fractional shortening (FS) and ejection fraction (EF) got increased, and the left ventricular end diastolic volume (LVEDV) and systolic volume (LVESV) got lower in the groups treated with high dose TS and simvastatin (P < 0.05 or P < 0.01), but difference between the two treated groups was insignificant. (2) Cardiac structure: As compared with the model group, the left ventricular dimension end diastole (LVDd) and systole (LVDs) in the groups treated with high dose TS and simvastatin got lower (P < 0.05 or P < 0.01). No treatment showed any effect on the thickness of ventricular wall. (3)Ventricular weight index: Both high dose TS and simvastatin could decrease the left ventricular weight index (LVWI) (P < 0.05).

CONCLUSIONTS could attenuate the left ventricular remodeling after acute myocardial infarction to certain extent, and improve cardiac function in the early phase after AMI, thus playing an important role in controlling morbidity and mortality of cardiac events and long-term prognosis.

Animals ; Cardiomegaly ; drug therapy ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Echocardiography ; Heart Ventricles ; pathology ; Hyperlipidemias ; blood ; complications ; drug therapy ; Lipids ; blood ; Male ; Myocardial Infarction ; complications ; diagnostic imaging ; drug therapy ; Organ Size ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; Tribulus ; Ventricular Remodeling ; drug effects

Objective To investigate the expression of caspase-10 in differentiated thyroid carcinoma and association with its development and metastasis. Methods Thyroid samples from 37 patients in a period from January 2006 to December 2007, with differentiated thyroid carcinoma were retrospectively analyzed for caspase-10 by immunohistocbemistry(streptavidin-perosidase, S-P), compared to control group of 46 cases with nodtdar goiter. The relationship between the expression of caspase-10 and the clinical pathologic characteristics of thyroid carcinoma were also explored simultaneously. Results caspase-10 were observed as brown or yellow particles located in the cytoplasm or cell membrane of nodular goiter but there were no significant evidence for its positive expression in thyroid carcinoma, caspase-10 expression was markedly down-regulated in differentiated thyroid carcinoma(29.73%,11/37) compared with benign nodules(71.74%,33/46, χ2=14.528, P<0.01). The positive expression in 18 cases with lymph node metastasis(11.11%,2/18) was significantly lower than those in 19 patients without lymph node metastasis(47.37%,9/19; χ2=4.210, P<0.01). There was no significant correlation(P> 0.05) between the expression of caspase-10 and the clinical pathologic characteristics including male, age, TNM stage and pathologic type. Conclusion Down-regulation of caspase-10 may play a critical role in carcinogenesis and development of differentiated thyroid carcinoma.

OBJECTIVETo investigate the reconstruction of skin defect at frontal and temporal hair line.

METHODS5 cases with skin defect at frontal and temporal hair line were treated with mastoid fasciocutaneous island flap pedicled with parietal branch of superficial temporal artery.

RESULTSAll the flaps survived completely. Hair grew up 5 - 7 days after operation, showing good reconstructed hair line.

CONCLUSIONSMastoid fasciocutaneous island flap is a reliable method for reconstruction of skin defect at frontal and temporal hair line.

Adult ; Carcinoma, Basal Cell ; surgery ; Carcinoma, Squamous Cell ; surgery ; Fascia ; transplantation ; Female ; Forehead ; injuries ; Humans ; Male ; Mastoid ; surgery ; Middle Aged ; Reconstructive Surgical Procedures ; Skin ; injuries ; Skin Neoplasms ; surgery ; Skin Transplantation ; Surgical Flaps

OBJECTIVETo study the effect of buffer on separate capacity of macroporous resin. To evaluate the quality of ferulic acid liposome and determine its entrapment efficiency.

METHODDifferent type of macroporous resin counterpoised by buffer system of Na2 HPO3-NaH2, PO3 was used to separate the free ferulic acid from the preparation and HPLC was used to determine the concentration of the ferulic acid to calculate the entrapment efficiency.

RESULTThis method had good linearity in the range of 0.56 - 2.8 g x mL(-1) (r = 0.999 6). The precision RSD was less than 1.1%. The adsorption effect of macroporous resin on liposome was reduced while it had no effect on the absorption ability of macroporous resin on the ferulic acid by the usage of buffer. The recovery of HPD450 resin on blank liposome was between 97.2% - 100.8%, while the average recovery is 98.1%.

CONCLUSIONBuffer system can enhance the separate ability of macroporous resin on liposome and free drug.

Adsorption ; Buffers ; Coumaric Acids ; administration & dosage ; analysis ; Drug Carriers ; Liposomes ; Quality Control ; Resins, Synthetic

A novel series of fingolimod analogues containing diphenyl ether moiety were designed and synthesized based on the modification of immunosuppressive agent fingolimod used in the treatment of multiple sclerosis. Compounds were evaluated in vivo for lymphopenic activity and heart rate affection. Most compounds showed moderate lymphopenic activity. It is worth noting that compounds 6c, 6d and 14c-14e showed considerable immunosuppressive activities comparable to fingolimod. And compound 14e had no effect on heart rate.
Animals ; Fingolimod Hydrochloride ; chemical synthesis ; pharmacology ; Heart Rate ; drug effects ; Immunosuppressive Agents ; chemistry ; Lymphopenia ; pathology ; Phenyl Ethers ; chemistry ; Structure-Activity Relationship

In this study, wheat germ agglutinin (WGA), tomato lectin (TL) and asparagus pea lectin (AL) were covalently coupled to conventional poly lactic-co-glycolic acid (PLGA) nanoparticles using a carbodiimide method to take the bioadhesive properties. The influences of the amounts of activating agents and lectins, as well as the activating time and incubating time on the effect of lectin conjugating were investigated to optimize the preparation conditions. The mean diameters of the performed nanoparticles with or without lectin conjugation ranged from (140.7 +/- 5.7) nm to (245.6 +/- 18.3) nm. The yields of lectin conjugating and the lectin surface concentrations on nanoparticles were determined by Lowry's methods, and were calculated to be (18.97 +/- 2.9)% - (20.15 +/- 2.4)% and (9.46 +/- 1.45)--(10.05 +/- 1.19) microg x mg(-1), respectively. The in vitro bioadhesive activities of nanoparticles were evaluated by pig gastric mucin (PM) binding experiments. After incubation at room temperature for 60 min, the equilibria of binding between nanoparticles and PM reached. The percentages of the bulk PM which had interacted with different lectin-conjugated PLGA nanoparticles were 15.5%, 12.1% and 11.8%, respectively. The conjugation of lectin enhanced the interaction about 2.4 - 3.2 fold compared with that of the non-conjugated one. A mathematical model was used based on the Langmuir equation, and the rate constants of interaction (k) were calculated to be 2.373 x 10(-3), 1.536 x 10(-3) and 1.714 x 10(-3) (microg x min/mL)(-1), respectively. These interactions could be competitively inhibited by their corresponding sugars of lectins. The results suggested that lectin-conjugated PLGA nanoparticles greatly promoted the interaction with PM in vitro compared with the conventional PLGA nanoparticles, thus would improve the bioadhesion on gastrointestinal mucosa after oral administration resulting in a prolonged residence time in the gastrointestinal tract.
Adhesiveness ; Drug Carriers ; Drug Compounding ; Drug Delivery Systems ; Gastric Mucins ; metabolism ; Lactic Acid ; chemistry ; metabolism ; Nanoparticles ; Plant Lectins ; chemistry ; metabolism ; Polyglycolic Acid ; chemistry ; metabolism ; Protein Binding ; Wheat Germ Agglutinins ; chemistry ; metabolism