Face ; Facial Paralysis ; Humans

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 evaluate the efficacy and safety of the interventional techniques for emergent treatment of iatrogenic renal injuries.Methods Nine patients with iatrogenic renal vascular injuries were treated with superselective renal arterial embolization.The causes of renal injury included post-renal biopsy in 5 patients,endovascular interventional procedure-related in 2,post-renal surgery in 1,and post-percutaneous nephrostomy in 1 patient.The patients presented clinically with hemodynamical unstability with blood loss shock in 7 patienrs,severe flank pain in 7,and hematuria in 8 patients.Perirenal hematoma was confirmed in 8 patients by CT and ultrasonography.The embolization materials used were microcoils in 7 and standard stainless steel coils in 2 patients,associated with polyvinyl alcohol particles(PVA)in 5,and gelfoam panicles in 2 cases.Results Renal angiogram revealed intra-renal arteriovenous fistula in 6 cases,intrarenal pseudoaneurysm in 2 cases,and the contrast media extravasation in 1 patient.The technical success of the arterial embolization was achieved in all 9 cases within a single session.All angiographies documented complete obliteration of the abnormal vessels together with all major intrarenal arterial branches maintaining patent.Seven patients with hemodynamically compromise experienced immediate relief of their blood loss related symptoms,and another 7 with severe flank pain got relief progressively.Hematuria ceased in 8 patients within 2-14 days after the embolization and impairment of renal function occurred after the procedure in 5 cases,including transient aggrevation(n=3)and developed new renal dysfunction(n=2).Two of these patients required hemodialysis.Perirenal hematoma were gradually absorbed on ultrasonography during 2-4 months after the procedures.Follow-up time ranged from 6-78 months(mean,38 months),4 patients died of other primary diseases of renal and multi-organ failures.Five patients are still alive without further intervention,and suffering no more of rebleeding and deterioration of renal function.Conclusions Transcatheter selective renal arterial embolization is safe and effective in the treatment of iatrogenic renal vascular injuries,resulting in permanent cessation of bleeding.(J Intervent Radiol,2007,16:807-810)

Objective To describe the manifestations of the inferior phrenic arteries(IPA)supply to the pulmonary hemorrhagic lesions and to evaluate the safety and efficacy of transcatheter arterial embolization(TAE)of the IPA.Methods The clinical data and imaging findings of eighteen patients with the additional blood supply to the pulmonary hemorrhagic lesions from the IPA were evaluated retrospectively.The causes of the bleeding were lung malignancies in 9,bronchiectasis in 7,and chronic inflammation in 2 patients.TAE supplementally was performed in patients with IPA supply to the pulmonary lesions,using polyvinyl alcohol particles,gelatin sponge particles,and microcoils.Results Selective arteriogram demonstrates an enlarged IPA,with numerous branches and hypervascularity in all 18 cases, with tumor staining in 9,the contrast material extravasation in 6,and non-specific staining in 2 cases.In addition,IPA-to-pulmonary shunting was found in 9 cases.All the lesions supplying by IPA were adjacent to the pleurae,including adjacent to the diaphragmatic pleura in 11,the mediastinal pleura in 5,and the lateral pleura of the lower lobe in 2 cases.Technical success of IPA embolization was achieved in the 18 cases.Embolization of other nonbronchial systemic arteries(the internal thoracic artery in 7 and intercostal artery in 3)was performed at the same session.All bleeding ceased immediately after supplemental IPA embolization.Follow-up time ranged from 8 months to 4 years.Mild recurrent hemoptysis occurred in 3 patients at 1,2,6 months respectively,after the embolization.These patients were responsive to conservative management.Recurrent bleeding did not occur in 15 patients during the follow-up. Conclusion The pulmonary hemorrhagic lesions,especially adjacent to the diaphragmatic and mediastinal pleurae,can be supplied by IPA,and may result in clinical failure following BAE.Supplemental TAE of IPA is a safe and effective adjunct to BAE in the management of bronchial bleeding supplied by IPA.

High-speed counter-current chromatography (HSCCC) was used to high performance separate and prepare lignans from Schisandrae chinensis fructus. The solvent system is composed of n-hexane-ethyl acetate-methanol-water (9 : 1 : 5 : 5) and n-hexane-ethyl acetate-methanol-water (9 : 1 : 9 : 5), speed is at 900 r.min-1, and flow rate is at 2.0 mL.min-1. Five fractions from Schisandrae chinensis fructus extract were separated and prepared with one HSCCC process. They were identified as schisandrin, gomisin J, schisandrol B, schisantherin A and deoxyschizandrin by electrospray ionization-multiple tandem mass spectrometry (ESI-MSn), respectively. Their contents were obtained in 98.74%, 94.32%, 99.53%, 94.23% and 98.68% by ultra high performance liquid chromatography (UPLC), separately. The rapid and simple method can be applied for the preparation of lignans from Schisandrae chinensis fructus.
Countercurrent Distribution ; Cyclooctanes ; chemistry ; isolation & purification ; Dioxoles ; chemistry ; isolation & purification ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Fruit ; chemistry ; Lignans ; chemistry ; isolation & purification ; Molecular Structure ; Plants, Medicinal ; chemistry ; Polycyclic Compounds ; chemistry ; isolation & purification ; Schisandra ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

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

AIMTo explore effects of Ginsenosides (Rb1, Rg1) on the expression of Bcl-2, Bax in the serum of kidney ischemia/reperfusion inducing apoptosis of HK-2 cells.

METHODSThe serum of rabbits with renal ischemia/reperfusion (SIR) and the control serum of rabbits (SC) were acquired and cultured with HK-2 cells. Detected apoptosis with TUNEL assay. The experiment was designed as: control group,ischemia/ reperfusion group, Rb1 blocking group and Rg1 blocking group. To detect the expression of Bcl-2, Bax with immunocytochemistry after 24 hours' cultured.

RESULTSThe expression of Bax in Rb1 blocking group and Rg1 blocking group were significantly decreased (P < 0.01), the ratios of Bcl-2/Bax were increased as compared with ischemia/reperfusion group.

CONCLUSIONRb1 and Rg1 have protective effects on apoptosis of HK-2 cells induced by serum of kidney ischemia/reperfusion.

Animals ; Apoptosis ; drug effects ; Cell Line ; Female ; Ginsenosides ; pharmacology ; Ischemia ; blood ; Kidney ; blood supply ; Kidney Tubules, Proximal ; cytology ; Male ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Rabbits ; Reperfusion Injury ; blood ; Serum ; physiology ; bcl-2-Associated X Protein ; genetics ; metabolism

The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.
Animals ; Apoptosis ; Aurora Kinase A ; antagonists & inhibitors ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Colonic Neoplasms ; pathology ; Humans ; Protein Kinase Inhibitors ; pharmacology ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; Xenograft Model Antitumor Assays

A series of novel sorafenib analogues were designed and synthesized. The cytotoxic activities of these compounds were tested in four tumor cell lines. Some of the compounds showed potent antiproliferative activity against the tested cell lines with IC50 = 4-20 micromol x L(-1). Some compounds demonstrated competitive antiproliferative activities to sorafenib against tested cancer cell lines. Among them, compound 7c demonstrated significant inhibitory activities on ACHN, HCT116 and MDA-MB-231 cell lines with IC50 values of 9.01, 4.97, 6.61 micromol x L(-1), respectively.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Inhibitory Concentration 50 ; Molecular Structure ; Niacinamide ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Phenylurea Compounds ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Objective To investigate the effect and significance of microglia/macrophage activation prior to cerebral ischemic preconditioning (CIP) in regulating toll-like receptors 2 (TLR2)/nuclear factor-kappa B (NF-κB) inflammatory signaling pathway in early stage after ischemic brain injury in rats.Methods Thirty healthy male SD rats were selected and divided into normal control group,sham operation group,ischemia group,intervention group and treatment group according to random number table,with six rats per group.A rat model of focal permanent cerebral infarct was established by occlusion of middle cerebral artery (MCAO).CIP was performed by local ischemia-reperfusion.Minocycline was used to inhibit microglia/macrophage activation after CIP.Features of microglia/macrophage activation after CIP were detected by immunofluorescence; mRNA expressions of predominant factors (NF-κB inhibitor α,IκB-α;tumor necrosis factor α,TNF-α) of TLR2/NF-κB inflammatory signaling pathway in parietal cerebral cortex by in situ hybridization method; death rate by Kaplan-meier survival curves; neurological deficits by a 5-point neurological scale; brain infarct size by triphenyl tetrazolium chloride (TTC) staining.Results Microglia/macrophage started activation at one hour after cerebral ischemic injury in preconditioning group and presented a significant increase at 12 hours.Speed and range of activation were higher in preconditioning group than in ischemic group.IκB-α mRNA in preconditioning group started expression at one hour.TNF-α mRNA in preconditioning group remained a low expression in 12 hours and had a significantly lower peak value as compared with that in ischemic group (P ＜ 0.05).CIP increased rat survival rate significantly,improved nerve function and reduced infarction size when compared with the ischemia group (P ＜ 0.05).Minocycline inhibited nerve protection by CIP significantly (P ＜0.05).Conclusion CIP induces rapid activation of microglia/macrophage in early period of rat cerebral ischemic injury and provides brain protection probably via inhibition of TLR2/NF-κB activity and inflammatory overreaction to cerebral ischemia.