Mesaconitine was incubated with rat liver microsomes in vitro. The metabolites of mesaconitine in rat liver microsomes were identified by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method with high resolution power. A typical reaction mixture of 100 mol L-1 Tris-HCI buffer (pH 7.4) containing 0.5 gL-1 microsomal protein and 50 micro molL-1 mesaconitine was prepared. The above reaction mixture was divided into six groups, and the volume of each group was 200 micro L. The incubation mixture was pre-incubated at 37 degrees C for 2 min and the reactions were initiated by adding NADPH generating system. After 90 min incubation at 37 degrees C, 200 micro L of acetonitrile was added to each group to stop the reaction. The metabolites of mesaconitine were investigated by UPLC-MS/MS method. Mesaconitine and 6 metabolites M1-M6 were found in the incubation system. The structures were characterized according to the data from MS/MS spectra and literatures. The metabolic reactions of mesaconitine in rat liver microsomes included the demethylation, deacetylation, dehydrogenation and hydroxylation. The major metabolic pathways of mesaconitine in rat liver microsomes were determined by UPLC-MS/MS on multiple reaction monitoring (MRM) mode combined with specific inhibitors of cytochrome P450 (CYP) isoforms, including alpha-naphthoflavone (CYP1A2), quinine (CYP2D), diethyldithiocarbamate (CYP2E1), ketoconazole (CYP3A) and sulfaphenazole (CYP2C), separately. Mesaconitine was mainly metabolized by CYP3A. CYP2C and CYP2D were also more important CYP isoforms for the metabolism reactions of mesaconitine, but CYP1A2 and CYP2E1 haven't any contribution to MA metabolism in rat liver microsomes.
Aconitine ; analogs & derivatives ; metabolism ; Animals ; Chromatography, High Pressure Liquid ; Cytochrome P-450 CYP3A ; metabolism ; Cytochrome P-450 CYP3A Inhibitors ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System ; metabolism ; Enzyme Inhibitors ; pharmacology ; Ketoconazole ; pharmacology ; Male ; Metabolic Networks and Pathways ; Microsomes, Liver ; enzymology ; metabolism ; Quinine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sulfaphenazole ; pharmacology ; Tandem Mass Spectrometry

Objective To assess the changes in heart geometry and function during off-pump coronary artery bypass grafting(CABG).Methods Thirty ASAⅡorⅢpatients(24 males,6 females)aged 50-78 undergoing elective off-pump CABG were studied.After induction of anesthesia and tracheal intubation a catheter which was connected to the monitor measuring continuous cardiac output(CCO),mixed venous blood oxygen saturation(S(?)O_2)and CEDV was placed via right internal jugular vein and the probe of multi-phase transesophageal echocardiograph(TEE)(Sonos HP 2500)was inserted in the esophagus.The distance between the probe and the incisors was between 34-45 cm.The hemodynamic variables and TEE parameters were recorded when epicardium was opened(T_1,baseline)when the octopus tissue stabilizer was placed during anastomosis between the graft vessel and left anterior descending artery(LAD)(T_2)left circumflex artery(LCX)(T_3)and right coronary artery(RCA)(T_4)and when the anastomoses between the vessel grafts and aorta was completed (T_5).Results At T_2 the mitral valve deceleration time(DT_1)and the blood flow through the mitral valve(Q_1) were decreased significantly as compared with the baseline(T_1);MAP was significantly decreased while HR and CVP were increased(P＜0.05).At T_3 the left and right ventricular end-diastolic diameter(LVEDD,RVEDD), tricuspid valve diameter(TVD)and the blood flow through Q_1 and tricuspid valve(Q_2)were significantly decreased as compared to the baseline values at T_1.The mitral valve E/A ratio was increased while the tricuspid valve E/A ratio was decreased(P＜0.05).The MAP,S(?)O_2,right ventricular end-systolic and end-diastolic volume(RVESV,RVEDV)and right ventricular ejection fraction were significantly decreased while HR and CVP were increased at T_3 as compared to the baseline at T_1.At T_4 LVESD,LVEDD,MVD,tricuspid valve E/A ratio and Q_1 were significantly decreased as compared to the baseline at T_1(P＜0.05).MAP,MPAP,SV,S(?)O_2, RVEF,RVESV and RVEDV were significantly decreased while HR and CVP were increased(P＜0.05).At T_5 all the TEE and hemodynamic parameters returned to the baseline valves at T_1.Conclusion During anastomoses between graft vessels and LAD,LCX and RCA,both left and right ventricles are compared to some extent and the heart function is impaired temporarily but returns to the baseline after the anastomoses are completed.

Amino Acids ; urine ; Animals ; Biogenic Monoamines ; metabolism ; urine ; Male ; Microwaves ; Rats ; Rats, Wistar

Using a UPLC-MS/MS (MRM) and cocktail probe substrates method, the metabolic fingerprint of the compatibility of Radix Aconite (RA) and Radix Paeoniae Alba (RPA) and its effect on CYP450 enzymes were investigated. These main CYP isoforms include CYP 1A2, CYP 2C, CYP 2E1, CYP 2D and CYP 3A. Compared with the inhibition effect of RA decoctions on CYP450 isoforms, their co-decoctions of RA and RPA with different proportions can decrease RA' inhibition on CYP3A, CYP2D, CYP2C and CYP1A2, but can not reduce RA' effect on CYP2E1. The metabolic fingerprints of RA decoction and co-decoctions with different proportions of RPA in CYP450 of rat liver were analyzed by UPLC-MS. Compared with the metabolic fingerprints of RA decoction, the intensity of diester-diterpenoid aconitum alkaloids decreased significantly, while the intensity of monoester-diterpenoid alkaloids significantly increased in the metabolic fingerprints of co-decoctions of RA and RPA. The results suggest that RA coadministration with RPA increased the degradation of toxic alkaloid and show the effect of toxicity reducing and efficacy enhancing.
Aconitum ; chemistry ; Alkaloids ; chemistry ; Animals ; Chromatography, High Pressure Liquid ; Cytochrome P-450 Enzyme Inhibitors ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Liver ; drug effects ; enzymology ; Metabolome ; Paeonia ; chemistry ; Rats ; Tandem Mass Spectrometry

OBJECTIVETo observe the efficacy of combination therapy of clomiphene and Chinese drugs for nourishing Shen and activating blood circulation (NSABC) in treating Stein-Leventhal syndrome caused sterility.

METHODSSixty-two patients with anovulation caused sterility were randomly divided into the treated group (n = 32) and the control group (n = 30). The treated grop was treated with the combination therapy and the control group treated by the same dosage of clomiphene alone.

RESULTSAfter treatment, when comparing with that before treatment, the endocrine hormones in the treated group improved significantly, showing a markedly decrease of androgen and luteotropic hormone, and increase of estrogen (P < 0.001). The periodic ovulation rate in the treated group reached 87%, the total pregnancy rate being 65.6%, with no occurrence of ovarian hyperstimulation syndrome (OHSS) and luteinized unruptured follicle syndrome (LUFS), while in the control group, the periodic ovulation rate was 66%, the total pregnancy rate 36.6%, with LUFS occurred in 4 patients. Comparison of the therapeutic effects between the two groups showed significant difference (P < 0.05).

CONCLUSIONThe combination therapy of clomiphene and NSABC has a better therapeutic effect in treating Stein-Leventhal syndrome caused sterility than that of using clomiphene alone.

Adult ; Androgens ; blood ; Anovulation ; blood ; etiology ; Clomiphene ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Infertility, Female ; blood ; drug therapy ; etiology ; Ovarian Hyperstimulation Syndrome ; prevention & control ; Ovulation Induction ; Phytotherapy ; Polycystic Ovary Syndrome ; blood ; complications ; drug therapy ; Progestins ; blood

OBJECTIVETo analyze the relationship between Chinese medical constitutions and chemotherapy-induced leucopenia (CIL) of primary breast cancer patients.

METHODSTotally 306 breast cancer patients undergoing adjunctive chemotherapy for the 1st time, and effective 291 breast cancer patients were recruited in this study.Nine Basic Constitutional Scale was used before first chemotherapy. Chinese medical constitutions were classified and quantitatively scored. The highest grading for any item of adverse reactions in each case during the whole chemotherapy course was recorded after chemotherapy. Data were statistically analyzed using SPSS16.0.

RESULTSThere was no significant difference in CIL between different chemotherapy regimens and various Chinese medical constitutions of breast cancer patients (P > 0.05). Yang deficiency constitution is one risk factor for CIL. The higher the score of yang deficiency constitution, the more severe the CIL.

CONCLUSIONSYang deficiency constitution was correlated with the degree of CIL. The higher the score of yang deficiency constitution, the greater the risk of III-IV grade CIL in breast cancer patients.

Breast Neoplasms ; complications ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Leukopenia ; chemically induced ; Medicine, Chinese Traditional ; Yang Deficiency

OBJECTIVETo explore the clinical outcomes of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) in treating osteoporotic vertebral compression fracture (OVCF).

METHODSFrom January 2007 to February 2010, the data of 40 patients with osteoporotic vertebral compression fracture underwent treatment were retrospectively analyzed. Of them,20 patients were treated with PVP (PVP group), there were 8 males and 12 females with an average age of (66.37 +/- 2.34) years old (54 to 81); 20 patients were treated with PKP (PKP group), there were 11 males and 9 females with an average of (65.12 +/- 3.21) years old (56 to 79). Postoperative at 1 week, 12 weeks, 1 year, pain and daily life function were respectively assessed by visual analogue scale (VAS) and Barthel index (BI); and anterior height of responsibility vertebra, Cobb angle were measured by X-rays.

RESULTSIn PVP group, 1 case complicated with bone cement leakage without clinical symptoms and no operation to treat. No postoperative infection and deep vein thrombosis were found between two groups. All patients were followed up more than 1 year, pain and daily life function has obviously improved than preoperative (P < 0.01); and there was no significant difference on 1 week, 12 weeks, 1 year after operation (P > 0.05); there was no significant difference between two groups (P > 0.05). In PVP group, there was no significant difference in anterior height of responsibility vertebra, Cobb angle before and after operation;and in PKP group, postoperative data has obviously improved than preoperative (P < 0.01), but there was no significant difference postoperative at 1 week, 12 weeks, 1 year (P > 0.05); there was no significant difference between two groups at 1 week, 12 weeks, 1 year after operation.

CONCLUSIONBoth the methods can obviously relieve pain and completely or partly recover daily life function in treating OVCF. But PKP has advantages of recovery of anterior height of responsibility vertebra and correction of Cobb angle, especially for serious compression.

Aged ; Aged, 80 and over ; Female ; Fractures, Compression ; diagnostic imaging ; physiopathology ; surgery ; Humans ; Kyphoplasty ; Male ; Middle Aged ; Osteoporotic Fractures ; diagnostic imaging ; physiopathology ; surgery ; Radiography ; Recovery of Function ; Retrospective Studies ; Spinal Fractures ; diagnostic imaging ; physiopathology ; surgery ; Spine ; surgery ; Treatment Outcome

Human tissue kallikrein-binding protein (Kallistatin, KAL), a secretory protein that participates in the regulation of multiple signaling pathways by binding to the extracellular receptor, however, at present has not been reported about the intracellular activity, and whether it has the similar biological activity with extracellular activity. Here we constructed no signal peptide KAL (NSK) into the adeno-associated virus vector to explore the intracellular activity of KAL. Both the endothelial cell and lung cancer cells could express KAL, but not secreted after rAAV2-NSK transfection. The proliferation and migration of human umbilical vein endothelial cells (HUVECs) were inhibited, but the apoptosis rate was not affected. The proliferation rates, mobility and tubule formation of all the three tested lung cancer cells, such as NCI-H446, NCI-H460 and A549, were inhibited to different extents. This cellular study not only confirmed the intracellular activity, but also suggested it may serve as a kind of "balance factor" in multi-targeted controlling, which may provide a new train of thoughts to explain the regulatory contradiction in PI3K-Akt signaling pathways by KAL.
Apoptosis ; Cell Proliferation ; Dependovirus ; Genetic Vectors ; Human Umbilical Vein Endothelial Cells ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; Serpins ; metabolism ; Signal Transduction ; Transfection

Objective:To compare the effects of auricular point intradermal needling with auricular point sticking on digestive symptoms and quality of life in patients undergoing platinum-based chemotherapy regimens. Methods:Ninety-six patients receiving platinum-based chemotherapy were randomly assigned to three groups using the random number table method,with 32 cases in each group.The control group received conventional nursing care plus 5-hydroxytryptamine receptor antagonist,and the other two groups received additional auricular point intradermal needling or sticking.For the three groups of participants,the acute and delayed vomiting and nausea severity,quality of life,and the additional antiemetic consumption rate were observed. Results:The three groups had no significant differences in the acute vomiting frequency and nausea severity and appetite(P>0.05)but had significant differences in the delayed vomiting frequency and nausea severity(P<0.05);the auricular point intradermal needling group won over the auricular point sticking group.The three groups showed significant differences in comparing the appetite in the delayed stage(P<0.05);both auricular point intradermal needling and sticking groups showed advantages over the control group(P<0.05),but no significant difference existed between the auricular point intradermal needling and sticking groups(P>0.05).There were significant differences in comparing the functional living index-emesis(FLIE)score in both acute and delayed stages among the three groups(P<0.05)and the result favored the auricular point intradermal needling group over the auricular point sticking group(P<0.05).The additional antiemetic consumption rate was higher in the control group than in the other groups(P<0.05). Conclusion:Based on the conventional nursing and 5-hydroxytryptamine receptor antagonist,adding either auricular point intradermal needling or auricular point sticking can lower the vomiting frequency and nausea severity in the delayed stage and improve appetite in patients receiving platinum-based chemotherapy regimen,but they have no notable impact on digestive symptoms in the acute stage;auricular point intradermal needling is superior to auricular point sticking in comparing the overall efficacy.Both auricular point intradermal needling and auricular point sticking can enhance the quality of life in patients undergoing chemotherapy and reduce their additional antiemetic consumption.

Sanjie Zhentong capsules were scanned by using a near infrared spectra probe with different drug mass fraction and the spectral information of capsule shells and contents in it were obtained. Then partial least squares (PLS) models were developed for the prediction of mass fraction of Fritillariae Thunbergii Bulbus and Resine draconis in Sanjie Zhentong capsules. The correlation coefficient (r9c)) and root mean standard error( RMSEC) of 0.949 5, 0.958 2 and 4.742 4, 4.135 7. The models obtained correlation coefficient (r(v)) of 0.919 2, 0.936 7 and root mean square error (RMSECV) of 6.158 9, 5.037 3 respectively in the training set. The paired T test analysis of statistics showed that there were no significant difference between predictive values and measure values. The established models reflected a strong prediction performance and can meet the needs of the production.
Capsules ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Least-Squares Analysis ; Spectroscopy, Near-Infrared ; methods