This study aims to investigate the change of plasma concentration of digoxin (DIG) in rats with ovariectomy. Twelve female SD rats were randomly assigned into ovariectomized group and sham group (n = 6). All rats plasma was collected after a single dose of 2 mg x kg(-1) DIG administrated orally, serum DIG concentration was determined by LC-MS/MS. The level of P-gp in the intestinal was analyzed by Western blotting. Pharmacokinetic calculations were performed on each individual using DAS 2.0 practical pharmacokinetic software. Compared with the sham group, C(max) of ovariectomized group decreased significantly (P < 0.01). There was no significant difference of AUC(0-t), and the level of P-gp was elevated in ovariectomized group. It was found that C(max) of DIG was significantly reduced after ovariectomy, and the change was associated with the decreased level of estrogen, which contributes to the increased level of P-gp.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Blotting, Western ; Chromatography, Liquid ; Digoxin ; blood ; pharmacokinetics ; Disease Models, Animal ; Estrogens ; blood ; Female ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

The study aims to establish a method for simultaneous determination of repaglinide and pravastatin sodium in rat plasma by LC-MS/MS and to study its pharmacokinetic interactions. Eighteen male SD rats were divided into repaglinide group, pravastatin sodium group and co-administration group. Blood samples were collected at different times after oral administration. Repaglinide and pravastatin sodium in rat plasma were separated by Agilent HC-C18 with the mobile phase consisting of methanol-0.1% formic acid (80 : 20). Detection and quantification were performed by using ESI-MS. The detector was operated in selected Reaction-monitoring mode at m/z 453.3-->230.1 for repaglinide, m/z 447.2-->327.4 for pravastatin sodium and m/z 285.1-->192.9 for diazepam as the internal standard. The calibration curve obtained was linear (R2>0.99) over the concentration range of 9.77-10,000 ng.mL-1 for repaglinide and 4.88-625 ng.mL-1 for pravastatin sodium. Compared with the single administration group, Cmax and AUC0-6h of repaglinide increased significantly (P<0.05) and tmax of pravastatin sodium prolonged (P<0.05) in co-administration group. The method is found to be simple, sensitive and accurate for determining the concentration of repaglinide and pravastatin sodium in rat plasma. There exists pharmacokinetic interactions in the co-administration of repaglinide and pravastatin sodium.
Administration, Oral ; Animals ; Carbamates ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Drug Interactions ; Male ; Piperidines ; administration & dosage ; blood ; pharmacokinetics ; Pravastatin ; administration & dosage ; blood ; pharmacokinetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

To compare the sampling errors from cluster or unequal probability sampling designs and to adopt the unequal probability sampling method to be used for death surveillance.Taking 107 areas from the county level in Shaanxi province as the sampling frame,a set of samples are drawn by equal probability cluster sampling and unequal probability designs methodologies.Sampling error and effect of each design are estimated according to their complex sample plans.Both the sampling errors depend on the sampling plan and the errors of equal probability in stratified cluster sampling appeares to be less than simple cluster sampling.The design effects of unequal probability stratified cluster sampling,such as πPS design,are slightly lower than those of equal probability stratified cluster sampling,but the unequal probability stratified cluster sampling can cover a wider scope of monitoring population.Conclusions:Results from the analysis of sampling data can not be conducted without consideration of the sampling plan when the sampling frame is finite and a given sampling plan and parameters,such as sampling proportion and population weights,are assigned in advance.Unequal probability cluster sampling designs seems to be more appropriate in selecting the national death surveillance sites since more available monitoring data can be obtained and having more weight in estimating the mortality for the whole province or the municipality to be selected.

Objective To compare diagnostic value of ~(18)F-fluoredeoxyglucose (FDG) PET/CT with contrast-enhanced CT in detecting primary hepatic carcinoma and postoperative recurrence.Methods Twenty-five cases of primary hepatic carcinoma or postoperative recurrent tumor underwent whole-body ~(18)F-FDG PET/CT and contrast-enhanced CT within one week's interval.They were retrospectively reviewed and the difierences between these two modalities were investigated.Results Of these 25 cases,there were 13 cases with primary hepatocellular carcinoma.1 case with intrahepatic cholangiocarcinoma and 11 cases with postoperative recurrence.The sensitivity of 18 F-FDG PET/CT and contrast-enhanced CT in diagnosing primary hepatic carcinoma was 78.6%(11/14) and 92.9%(13/14),and sensitivity in diagnosing postoperative recurrent was 100.0%(11/11) and 63.6%(7/11) respectively.Conclusion Contrast-enhanced CT may have a slight advantage over PET/CT in detecting primary hepatic carcinoma,but ~(18)F-FDG PET/CT combined with contrast-enhanced CT has even greater accuracy.Meanwhile,~(18)F-FDG PET/CT has better diagnostic accuracy in detection of postoperative recurrent tumor.

Objective To explore the influencing factors of bleeding in patients with cerebral arteriovenous malformation (AVM) through observing the angioarchitecture of AVM with cerebral DSA.Methods The clinical and imaging data of 199 patients with AVM, including 107 with bleeding and 92without bleeding, were retrospectively analyzed. The relationships between bleeding and such factors as the site and size of masses, the type and site of supplying arteries, the number and pathway of venous drainage, having vascular tumor-like changes or not, the relation between AVM and aneurysm in terms of location, and the number and size of concurrent aneurysms were determined by univariate analyses and Binary logistic regression with SPSS13.0. Results Univariate analysis indicated that such factors as micro-sized (0.5-1.0 cra) and small-sized (1.0-2.0 cra) masses ofAVM, AVM underdeep location,having exclusively deep draining veins, fewer draining veins and deep feeding arteries, concurrent small aneurysms (＜5 mm), aneurysms at the end of the blood-supply artery were positively correlated to hemorrhagic presentation. The number of feeding arteries and the number of concurrent aneurysms were not correlated with hemorrhagic presentation. Having vascular tumor-like changes can decreased the risk of bleeding. When stepwise multiple logistic regression analysis was employed, only micro-sized and small-sized masses of AVM, having deep feeding arteries, and aneurysms at the end of the blood-supply artery were dependent predictors of hemorrhagic presentation. Conclusion Micro-sized and small-sized masses of AVM, having deep draining veins and aneurysms at the end of the blood-supply artery are the most powerful risk predictors for hemorrhagic AVM presentation.

The amino acid sequence of the fusion protein FP3 was measured by two types of LC-MS/MS and its primary structure was confirmed. After reduction and alkylation, the protein was digested with trypsin and glycosyl groups in glycopeptide were removed by PNGase F. The mixed peptides were separated by LC, then Q-TOF and Ion trap tandem mass spectrometry were used to measure b, y fragment ions of each peptide to analyze the amino acid sequence of fusion protein FP3. Seventy-six percent of full amino acid sequence of the fusion protein FP3 was measured by LC-ESI-Q-TOF with the remaining 24% completed by LC-ESI-Trap. As LC-MS and tandem mass spectrometry are rapid, sensitive, accurate to measure the protein amino acid sequence, they are important approach to structure analysis and identification of recombinant protein.
Amino Acid Sequence ; Chromatography, High Pressure Liquid ; Molecular Sequence Data ; Peptide Mapping ; Recombinant Fusion Proteins ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tandem Mass Spectrometry ; Vascular Endothelial Growth Factor A ; antagonists & inhibitors ; chemistry

OBJECTIVETo investigate the cough-relieving, analgesic and antibiotic effects of durian shell extract (DSE) in relieving cough and its analgesic and antibiotic effects.

METHODSThe effect of DSE in relieving cough was assessed in mice challenged with ammonia and SO(2) to induce coughing. The analgesic and antibiotic effects of DSE in mice were evaluated by hot plate test and twisting reaction induced by acetic acid, and by minimal inhibitory concentration (MIC) and disc-agar diffusion tests, respectively.

RESULTSCompared with the control group, the mice treated with 300 and 900 mg/kg DSE showed significantly prolonged latency with decreased number of coughing induced by ammonia and SO(2), and the effect was dose-dependent. DSE markedly prolonged the latency and decreased the twisting number of the mice induced by acetic acid without affecting the pain threshold in hot plate test. DSE produced no significant inhibitory effects against Staphylococcus aureus, Staphylococcus epidermidis, or E. coli, and showed a week inhibition against Bacillus aeruginosus.

CONCLUSIONDSE shows obvious effect in relieving cough and produces better analgesic effect against chemical factor-induced pain than against physical agent-induced pain sensation. DSE has a moderate inhibitory effect against Bacillus aeruginosus.

Analgesics ; pharmacology ; Animals ; Anti-Bacterial Agents ; pharmacology ; Antitussive Agents ; pharmacology ; Bombacaceae ; chemistry ; Male ; Mice ; Plant Extracts ; pharmacology ; Random Allocation

The primary structure of TNK-tissue plasminogen activator (TNK-tPA) was characterized using liquid chromatography-mass spectrometry (LC-MS). Firstly, the molecular mass of deglycosylated protein was measured. Then peptide mass mapping and MS/MS of the reduced, alkylated and trypsin-digested sample were tested and analyzed so as to verify its amino acid sequence and identify post-translational modifications. Results show that the amino acid sequence was consistent with designed structure; about 5% of M207 was oxidized; T61 was fucosylated with -80% occupancy; N103, N448 and N184 (-15% occupancy) were glycosylated with complex-type oligosaccharides. LC-MS coupled with proper sample pretreatment is approved to be a rapid and powerful approach to characterize the primary structure of TNK-tPA.
Amino Acid Sequence ; Chromatography, Liquid ; Glycosylation ; Mass Spectrometry ; Molecular Weight ; Protein Processing, Post-Translational ; Tissue Plasminogen Activator ; chemistry

OBJECTIVETo evaluate the influence of Chinese drug Dahuang Zhechong pill on the hepatocellular function.

METHODThirty-seven patients with hepatocirrhosis and twelve normal controls were performed the hepatobiliary scintgraphy with Tc-99m labeled ethylene hepatobiliary iminodiacetic acid (99 mTc-EHIDA), and the biochemical examination of hepatic function. There was 19 cases repeated the imaging after 6 months treated with chineses drug. By the three compartmental model configurations, the function parameters of hepatocellular extraction and excretion were calculated.

RESULTIn the hepatocirrhosis groups, the hepatocellular uptake peak time and mean residence index were higher than those in normal controls (P < 0.01). Compared to normal controls, the uptake index, uptake speed index and descendent speed index were decreased markedly (P < 0.05). After treatment for 6 months with Chinese drug, the level of serum transaminase, globulin and bilirubin was lower than that before treatment. The uptake peak time and mean residence index decreased notably after treatment for 6 months (P < 0.01), and the uptake index increased, (P < 0.05).

CONCLUSIONChinese drug Dahuang Zhechong pill may improve the hepatocellular function and liver function status in patients with hepatocirrhosis.

Adult ; Bilirubin ; blood ; Drugs, Chinese Herbal ; pharmacology ; Globulins ; metabolism ; Hepatocytes ; drug effects ; metabolism ; Humans ; Liver Cirrhosis ; blood ; drug therapy ; metabolism ; Liver Function Tests ; Male ; Middle Aged ; Transaminases ; blood

Effervescent technique, which can accelerate drug disintegration and dissolution, is usually applied in quick release preparations. Along with the development of pharmaceutical technique and theory, effervescent technique is used more and more extensively to adjust the behavior of drug release, such as in sustained and controlled release preparations, pulsatile drug delivery systems, and so on. This review demonstrated the new applying of effervescent technique in effervescent tablets, stomach floating forms, osmotic pump tablets and pulsatile drug delivery systems, adding to the critical common technique of effervescent forms in drug research. This will be benefit for the further research and development of effervescent technique.
Dosage Forms ; Drug Delivery Systems ; Humans ; Osmosis ; Pharmaceutical Preparations ; administration & dosage ; Tablets