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 assess the feasibility of using PET molecular imaging to evaluate the therapeutic effects of traditional Chinese medicine FuZhiSan (FZS) on the model of aging Alzheimer's disease (AD) rats. Methods Twenty aged AD rats (Sparague-Dawley rats,male) were randomly divided into FZS treated group (n = 10) and control group (n = 10). Another 10 healthy adult rats were as blank controls. Morris water maze record system was used for cognitive function assessment. Before and after FZS treatment 18 F-fluorodeoxyglucose (FDG) and 11 C-2- [4'-(methylamino) phenyl] benzothiazol-6-ol ( PIB )PET imaging was undertaken. After post-treatment imaging procedures the brain tissues of all animals were taken for histochemical study,such as staining with HE,congo red,amyloid β (Aβ) immunofluorescence,5-bromo-2-deoxyuridine (BrdU) immunofluorescence and NeuN immunofluorescence. Paired t-test was performed with SPSS 13.0 software for the data analysis. Results The cognitive dysfunction of aging AD rats was improved after FZS treatment. The escape latency in FZS treated group was significantly shorter than that of control group ((32.5 ±10.8) s vs (102.6±8.8) s,t =15.7987,P=0. 0001). Diffuse neuronal loss and Aβ deposition were detected in the hippocampus and cortex in the aged AD rats. The imaging data showed that brain glucose metabolism was amended in FZS treated group while the abatement of amyloid deposition was not significant. Immunofluorescence results indicated that the neuronal proliferation was more remarkable in FZS treated group. Conclusions It may be feasible to use PET imaging as a method to evaluate the therapeutic effect in AD rats. FZS may ameliorate memory dysfunction of aged AD rats. Its mechanism may be partly contributed to the enhancement of the neuronal proliferation and survival.

Objective To investigate the imaging characteristics of both intra- and extrathoracic sarcoidosis on 18F-FDG PET/CT.Methods From 2007 Aug.to 2009 Nov.,22 patients( 10 males,12 females) with sarcoidosis,confirmed by pathological study and clinical follow-up,underwent 18 F-FDG PET/CT imaging.The imaging patterns of intrathoracic and extrathoracic lesions were analyzed.The patterns were classified as the typical or atypical ( symmetrical or asymmetrical FDG accumulation and enlargement of hilar lymph nodes) based on PET and CT separately.Nonparametric McNemar test,independent t-test and Fisher exact test were applied for statistical analysis.Results For typical pattern vs atypical pattem identification,PET was significantly different from CT ( 18 and 4 vs 12 and 10,P =0.031 ).In those with atypical pattern demonstrated by CT alone at hilar region,PET showed either symmetrical or asymmetrical accumulation of FDG.Except for mediastinal lymph nodes involvement,lung parenchyma was the second common site ( 19/22,86.4％ ),followed by lymph nodes at abdomen and (or) pelvis ( 12/22,54.5％ ).Conclusion The imaging characteristics of both intra- and extrathoracic sarcoidosis on 18F-FDG PET/CT may be helpful for the diagnosis of atypical sarcoidosis on CT image alone.

To explore advantages of Chinese medicine (CM) by analyzing differences in the origin of philosophy for human health between CM and Western medicine (WM). Methodologically, a distinctive feature of CM is its systems theory, which is also the difference between CM and WM. Since the birth of CM, it has taken the human body as a whole from the key concepts of "qi, blood, yin-yang, viscera (Zang-Fu), and meridian and channel", rather than a single cell or a particular organ. WM evolves from the Western philosophic way of thinking and merely uses natural sciences as the foundation. The development of WM is based on human structures, or anatomy, and therefore, research of WM is also based on the way of thinking of decomposing the whole human body into several independent parts, which is the impetus of promoting the development of WM. The core of CM includes the holistic view and the dialectical view. Chinese herbal medicines contain various components and treat a disease from multiple targets and links. Therefore, Chinese herbal medicines treat a diseased state by regulating and mobilizing the whole body rather than just regulating a single factor, since the diseased state is not only a problem in a local part of the body but a local reflection of imbalance of the whole body.
Holistic Health ; Humans ; Integrative Medicine ; Medicine ; Medicine, Chinese Traditional ; Philosophy ; Systems Biology ; Western World

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

OBJECTIVETo assess the features of fluorine-18 fluorodeoxyglucose (FDG) uptake in patients with benign pulmonary nodules.

METHODSFrom October 1998 to July 2004, 47 patients with benign pulmonary nodules were imaged with FDG-positron emission tomography (PET). Diagnoses were confirmed by surgery. FDG-PET data was analyzed by visual method and semi-quantitive method. When pulmonary nodules with abnormal FDG intake appeared in PET scans confirmed by visual method, their maximum and mean standard uptake value (SUVmax and SUVmean) and SUV of normal lung (SUVlung) were measured using semiquantitative method.

RESULTSTwenty-one cases showed nothing abnormal in PET scans, including 17 calcification and fibrosis, 2 hamartomas and 2 sclerosing hemangiomas. 26 pulmonary nodules were detected by FDG-PET (17 active tuberculous, 6 inflammatory pseudotumors, 3 cryptococcosis). FDG uptake of these 26 nodules was higher than that of normal lung (SUVmax, SUVmean and SUVlung were 3.04 +/- 1.65, 2.48 +/- 1.35 and 0.40 +/- 0.07, respectively, P < 0.001). Correlations were not found between FDG uptake and nodule size or SUV of normal lung or age or blood glucose level in these 26 patients (P > 0.05). SUV in 9 cases (9/26, 35%) were beyond 2.5.

CONCLUSIONSSome benign pulmonary nodules were FDG avid.

Adult ; Aged ; Diagnosis, Differential ; Female ; Fluorodeoxyglucose F18 ; pharmacokinetics ; Humans ; Lung Neoplasms ; diagnostic imaging ; Male ; Middle Aged ; Radionuclide Imaging ; Radiopharmaceuticals ; pharmacokinetics ; Retrospective Studies ; Sarcoidosis, Pulmonary ; diagnostic imaging ; Solitary Pulmonary Nodule ; diagnostic imaging ; Tuberculosis, Pulmonary ; diagnostic imaging

Objective To determine the value of 2-18F-2-deoxy-β-D-glucose (18F-FDG)PET/CT in malignancy tumor detection of patients suspected as having paraneoplastic syndrome (PNS).Methods The clinical data of 54 patients suspected as having PNS, underwent PET/CT study in our hospital fiom June 2007 to December 2009, were retrospectively analyzed. The efficacy of 18F-FDG PET/CT on positive detection rate, positive predictive value of malignant tumors and on the detection of malignant tumor markers were analyzed with the results of pathological findings and clinical data;whether the course of disease could affect these detection was also analyzed. Results Positive results of 18F-FDG PET/CT were noted in 17 patients (31.5%), and 13 of them were confirmed as malignant tumors with pathological results. The positive predictive value of 18F-FDG PET/CT was 76.5%. The durations of patients with malignancies were not different from those of patients without malignancies.PET/CT enjoyed a significantly higher efficacy rate in identifying malignant tumors in patients with elevated tumor markers than in patients with tumor markers in normal range (P＜0.05). Conclusion 18F-FDG PET/CT improves the tumor detection rate in PNS suspects, especially in patients enjoying elevated tumor markers.

Objective: To evaluate the antioxidant activity, antiglycation property, and bioactive components content of different solvent extracts from Chinese olive (Canarium album L.) fruit. Methods: The dry powder of Chinese olive fruit was extracted with different solvents, i.e., water, water/ethanol (1/1, v/v), ethanol, methanol, acetone and ethyl acetate. The total phenolic, total flavonoids and total triterpenoids contents of various extracts were determined by spectrophotometric methods. Phenolic compounds were identified by high performance liquid chromatography. The assayed antioxidant activity was determined in vitro models such as antioxidant capacity by radical scavenging activity using 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), 1,1-diphenyl-2-picryl- hydrazyl (DPPH) and nitrite oxide methods, chelating activity on metal ions, lipid and protein peroxidation methods. In vitro glucose-bovine serum albumin assay was used to evaluate the antiglycation of various extracts. Results: The water/ethanol extracts of Chinese olive fruit exerted significant scavenging effects on free radicals and strong inhibitory effects on advanced glycation end products formation. The Chinese olive fruit extracts were rich in phenolic compounds and triterpenoids. Gallic acid, ferulic acid and rutin were identified from the water/ethanol extracts. Correlation analysis indicated that there was a linear relationship between the antioxidant potency, free radical scavenging ability and phenolic compounds content of the Chinese olive fruit extracts. Conclusions: Chinese olive fruit could be a natural candidate for studies of dietary complement to diabetes treatment since it combines antioxidant and antiglycation activities.

OBJECTIVETo explore the effects of chloride channels on the regulation of platelet cytoplasmic free calcium concentration ([Ca2+]i) and platelet aggregation (PAG).

METHODSFreshly separated platelets were activated by thrombin. Chloride channel blockers DIDS or NFA and calcium channel blockers SK&F96365 or nifedipine were added to study the effects on platelet [Ca2+]i and PAG by a single reagent or the combination of reagents and find out the interactions among DIDS, NFA, SK&F96365 and nifedipine.

RESULTSBoth DIDS and NFA could inhibit the thrombin (1 U/ml) induced PAG in a dose-dependent manner, whereas had little effect on resting [Ca2+]i. As compared with the control group, DIDS, SK&F96365 and Nifedipine could significantly reduce the PAG, Ca2+ release and Ca2+ influx in thrombin activated platelet (P < 0.05). The combination of DIDS and SK&F96365 had greater effects in reducing the PAG, Ca2+ release and Ca2+ influx than either reagent alone (P < 0.05). The combination of DIDS and nifedipine also had greater effect than each alone in reducing Ca2+ release (P < 0.05). The combination of NFA and SK&F96365 weakened each other's effect on Ca2+ release (P < 0.05), while NFA and nifedipine weakened each other's effects on PAG, Ca2+ release and Ca2+ influx in thrombin activated platelet (P < 0.05).

CONCLUSIONDIDS and NFA have no effect on the resting [Ca2+]i and the leak calcium influx of platelet. DIDS can inhibit the Ca2+ release, Ca2+ influx and PAG of platelet induced by thrombin, while NFA can only inhibit the Ca2+ release. The chloride channel and calcium channel blockers have interactions in affecting resting [Ca2+]i and PAG of platelet. The opening of chloride channel can influence the cellular calcium movement of platelet.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid ; pharmacology ; Adult ; Blood Platelets ; cytology ; drug effects ; metabolism ; Calcium ; metabolism ; Calcium Channel Blockers ; pharmacology ; Cells, Cultured ; Chloride Channels ; antagonists & inhibitors ; physiology ; Cytoplasm ; drug effects ; metabolism ; Drug Interactions ; Humans ; Imidazoles ; pharmacology ; Nifedipine ; pharmacology ; Niflumic Acid ; pharmacology ; Platelet Aggregation ; drug effects ; Thrombin ; pharmacology

OBJECTIVETo investigate the effect of valproic acid on the expression of P27(Kip1) and P170 and drug resistance of leukemia HL60/HT cell line and explore its possible mechanisms.

METHODSHL-60/HT cells were derived from HL-60 cells induced by harringtonine (HT) in gradient concentrations. The inhibitory effect of valproic acid on the proliferation of HL-60 and HL-60/HT cells was evaluated by MTT assay, and the P27(Kip1) expression, P170 expression and cell cycle of the cells were analyzed with flow cytometry.

RESULTSThe multidrug-resistant HL-60/HT was acquired, which showed a stable drug-resistant index with increased IC(50) of HT, VCR, DNR and Ara-c by 9.30, 5.20, 4.91 and 3.65 folds, respectively, as compared with those of HL60 cells. The expression of P27(Kip1) in HL-60/HT cells was significantly lower but P170 expression significantly higher than that of HL-60 cells and normal mononuclear cells (P<0.05). The expressions of P27(Kip1) and P170 showed no significant difference between normal mononuclear cells and HL-60 cells. The growth inhibition rate of VPA combined with Ara-C was significantly higher than that of valproic acid or Ara-C alone in HL-60/HT cells and HL-60 cells (q=1.37 and 1.51, respectively). HL-60/HT and HL-60 cells cultured in the presence of VPA resulted in a significant increase in the expression of P27(Kip1) and the G(1)-phase cells (P<0.05), but the expression of P170 underwent no significant changes (P>0.05).

CONCLUSIONHL-60/HT cells have lower P27(Kip1) expression compared with HL-60 cells. Valproic acid can inhibit the growth of HL-60/HT cells and enhance their Ara-C sensitivity possibly by increasing P27(Kip1) expression and causing cell cycle arrest in G(1) phase.

Antineoplastic Agents ; pharmacology ; Cyclin-Dependent Kinase Inhibitor p27 ; genetics ; metabolism ; Cytarabine ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Glycoproteins ; genetics ; metabolism ; HL-60 Cells ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Valproic Acid ; pharmacology