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 study the protective effects of Tianma xingnao capsule on brain blood circulation in mice and rats.Methods The arteria carotis externa was ligated,and arteria carotis interna was kept.The left carotid artery was exposed and placed over an ultrasonic flow probe.The brain flow volume was recorded with an Ultrasonic Volume.The pursiness time of mice was observed to evaluate the effect of Tianma xingnao capsule on cerebral ischemia and anoxia.The permeability of normal blood-cerebral barrier was investigated in mice.Results Tianma xingnao capsule significantly increased brain blood flow and prolonged mouse pursiness time.Tianma xingnao capsule at a dose of 4 g/kg significantly elevated the content of Evans in mouse brain.Conclusions Tianma xingnao capsule can increase the brain blood flow in rats and improve brain blood circulation in mice.It is obviously advantageous to protect against cerebral ischemia and hypoxia.

Objective To investigate effects of Naoxintong drip pill (NDP) in activating blood and removing blood-stasis and on myocardial and cerebral ischemia. Methods The in-vivo effect of NDP on thrombosis, aggregation of platelets, blood viscosity, microcirculation, acute myocardial and cerebral ischmia and the focal cerebral-infarction were observed for study the pharmacodyamic effect of NDP. Results NDP could significantly inhibit the formation of thrombosis and maximal aggregation rate of platelets, and decrease viscosity in whole blood and plasma in rats with blood stasis. It could also promote auricular microcirculation, prolong the survival time of mice with cerebral ischemia, improve the electrocardiogram of ischemic rats, reduce the focal cerebral-infarction area and improve behavior disorder. Conclusion NDP possesses actions of activating blood and removing blood-stasis and improving myocardial and cerebral ischemia and focal cerebral-infarction.

Objective To explore the mediator effect of coping styles in relationship between hope level and subjective well-being of empty-nesters in urban community.Methods 208 empty-nesters were tested with Herth Hope Scale,Coping Style Questionnaire and Subjective Well-Being to investigate the influence and the pathways of hope and coping styles on subjective well-being with structural equation modeling.Results Influence of hope level on subjective well-being of empty-nesters in urban community accorded with completely-mediated model (x2/df =1.971,GFI =0.955,AGFI =0.911,RMSEA =0.068),and influence of hope level mediated by positive coping styles accounted for 41.76％(Z=3.692,P＜0.01).Conclusion The influence of hope level on subjective well-being is mediated mainly by positive coping styles for empty-nesters in urban community.

Arbuscular mycorrhizal fungi can infect the roots of Cercidiphyllaceae and form arbuscular mycorrhizae.Infection rate is from 12% to 30%,but infection strength is weak.4 species of Acaulospora and 11 species of Glomus were isolated and identified,including Acaulospora tuberculata,A.spinosa,A.foveata,A.denticulate,Glomus geosporum,G.clarum,G.constrictum,G.monosporum,G.laroideum,G.versifome,G.microcarpum,G.mosseae,G.hoi,G.halonatum and G.reticulatum.Among them,G.cercidiphyllorum is advantage species.So AMF may be a potent resource of biology which can stimulate the growth of Panax notoginseng.

Objective To evaluate the usefulness of serum galactemannan(GM) for the diagnosis of invasive pulmonary aspergillosis (IPA) in critically ill patients. Methods Study was conducted between February 2007 and July 2008. Included patients on admission ICU who suffer from suspected IPA. GM test and culture were collected 2 weekly. Chnical feature, mycological evidence and optical density index (ODI) were noted. Clinically invasive fungal infection(IFI) were defined proven, probable and possible. The patients were classified into neutropenia, non-neutropenia and treated with immunosuppressive agents, non-neutropenia and non-immunosuppressive agents. To compared of the sensitivity and specificity of GM in different patients. Results 94 patients were included, 4 patients were proven, 29 patients were probable, 34 patients were possible IFI, 27 patients were non-IPA. The positive rate of the GM was 31.9% (30/94). The sensitivity and specificity of GM in proven cases and probable cases are 66.7% and 92.6%. GM assay tended to become positive earlier than the culture 2-10(5.33±2.17)d. We found that differences in patient diagnosis and selection might account for the disparities seen for positive rate for the GM test. There was positive in three of the four patients with proven, the positive rate of GM was 65.5% for probable cases, for possible cases was 17.6%, for non-IPA cases was 7.4% (P=0.001). For patient with neutropenia , treated with immunosuppressive agents and without immunosuppressive agents, the positive rate of GM was 52.9%vs 41.7% vs 34. 6% (P=0.015) ;the sensitivity was 80.0% vs 70. 0% vs 53.8% (P=0.011), the ODI was 1.365 (0.582-6.736) vs 1. 123 (0. 623-6.868) vs 0.554 (0.522-0.823), P=0. 005, respectively. Conclusion These results show that GM test is useful for early diagnosis IPA in critically ill patients. Differences in patient selection and diagnosis might account for the disparities seen for positive rate and sensitivity for the GM test. It has been higher sensitivity and ODI in the patient treated by immunosuppressive agents.

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

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

Objective To investigate the effect of silk fibroin scaffolds seeded with adipose mesenchymal stem cells (ADMSCs) in remodeling fiber for tunica albuginea defect in rabbits.Methods Fifty-six New Zealand rabbits were divided into 4 groups according to the random number table after a defect was created in the tunica albuginea:Group A (the defect was repaired with silk fibroin),Group B (with silk fibroin seeded with ADMSCs),Group C (with autologous tunica vaginalis) and Group D (left unrepaired),with 14 rabbits per group.Tunica albuginea sections were obtained for HE staining,Sirius red staining,Hart staining and immunofluorescence staining of macrophages at 6 and 12 weeks after surgery.Results At 12 weeks after surgery,HE staining revealed chaotically distributed new fiber ingrowth in Group D and orderly ingrowth in Groups A,B,and C.At 12 weeks after surgery,Sirius red staining revealed mean area of type Ⅰ collagen fibers was greater than that of type Ⅲ in Groups A (98 780 ±4 190 vs 51 177 ±5 464),B(94 855 ±9 010 vs 50 815 ±3 895),and C(99 860 ±6 015 vs 50 948 ± 6 595),but the difference in area of collagen fiber of the same type was insignificant among the three Groups.Moreover,less type Ⅰ collagen fibers (79 386 ±2 237) and more type Ⅲ collagen fibers (85 278 ± 2 645) were observed in Group D compared with other three Groups (P ＜ 0.01).At 12 weeks after surgery,Hart staining showed the mean area of elastic fibers in Groups A,B,C,and D was 2 805 ± 90,2 849 ±84,3 068 ±485,and 1 961 ±96 respectively.There was no statistical difference between Groups B and C,but less amount of fibers was observed in Group A (P ＜ 0.01) and least amount was observed in Group D (P ＜0.01).At 6 weeks after surgery,the number of infiltrating macrophages in Groups A,B,C and D was 4.10 ± 0.87,3.80 ± 0.78,3.70 ± 0.94,and 6.80 ± 1.63 respectively.There was no statistical difference in the number of macrophage infiltration among Groups A,B and C,but all were lower than that in Group D (P ＜ 0.01).Conclusion Silk fibroin seeded with ADMSCs is comparable to autologous grafts for repair of tunica albuginea defect in rabbits.

OBJECTIVETo investigate the effects of ginkgolides injection on experimental cerebral ischemia and its related mechanism of action.

METHODThe middle cerebral artery occlusion (MACO) model was induced by the FeCl3-occluding method to explore the protective effects of ginkgolides injection on the score of neurological deficits, the rate of cerebral infarction and the histomorphology of cerbral ischemia in rats. Thrombosis formation in vivo was induced by adrenaline-collagen in mice to explore the antithrombotic effect. Platelet aggregation was induced by ADP and hemorrheological parameters with hyper-viscosity by dextran T-500 were used to explore the effects of antiplatelet aggregation and decreasing viscosity of blood.

RESULTGinkgolides injection could markedly decrease the infarct size and behavior deficits score, inhibit the thrombus formation in mice, decrease blood viscosity and ameliorate hemorrheological parameters in rat.

CONCLUSIONGinkgolides injection has the protective effects on focal cerebral ischemia, and its mechanism may be relative to its inhibition of platelet-dependent thrombosis and amelioration of hemarheological partments.

Animals ; Behavior, Animal ; drug effects ; Blood Viscosity ; drug effects ; Brain ; pathology ; Female ; Ginkgo biloba ; chemistry ; Ginkgolides ; administration & dosage ; isolation & purification ; pharmacology ; Infarction, Middle Cerebral Artery ; pathology ; physiopathology ; Injections ; Intracranial Thrombosis ; pathology ; Male ; Mice ; Neuroprotective Agents ; administration & dosage ; isolation & purification ; pharmacology ; Platelet Aggregation ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley