This paper is to report the study of the metabolism of lidamycin in vitro including in plasma and microsomes to guide clinical therapy. Lidamycin was quantified by detecting its active ingredient using HPLC-MS/MS. The metabolic stability of lidamycin in rat, Beagle dog, monkey and human plasma and liver microsomes, and its inhibition to cytochrome P450 isoforms in human liver microsomes were studied. Results showed that lidamycin was metabolized in the four species of plasma, and the sequence of metabolic rates in plasma were in rat > in dog > in human > in monkey. But among the four species of liver microsomes, lidamycin was metabolized only in monkey liver microsomes. There was almost no inhibition to cytochrome P450 isoforms at the concentrations of between 0.0005 and 10 ng x mL(-1). Therefore, the property of lidamycin metabolism in human is similar with that in dog, and metabolism of other drugs would not be decreased by cytochrome P450 as used along with lidamycin in clinic.

This paper is to report the study of the metabolism of forscolin in plasma and liver microsomes for guiding clinical therapy. Forscolin was quantified by HPLC-MS/MS. The metabolic stability of forscolin in rat, Beagle dog, monkey and human plasma and liver microsomes, mediated enzymes of forscolin and its inhibition on cytochrome P450 isoforms in human liver microsomes were studied. Results showed that forscolin was not metabolized in plasma of the four species but metabolized in liver microsomes of the four species. The t1/2 of forscolin in rat, Beagle dog, monkey and human liver microsomes were (52.0 +/- 15.0), (51.2 +/- 5.9), (6.0 +/- 0.2) and (11.9 +/- 1.8) min; CL(int) were (75.6 +/- 18.7), (60.9 +/- 6.8), (513.8 +/- 14.3) and (176.2 +/- 25.6) mL x min(-1) x kg(-1); CL were (34.8 +/- 4.5), (23.3 +/- 1.0), (40.3 +/- 0.5) and (17.9 +/- 0.3) mL x min(-1) x kg(-1), respectively. Forscolin was metabolized by CYP3A4 in human liver microsomes. There was definite inhibition on CYP3A4 at the concentrations of forscolin between 0.1 ng x mL(-1) and 5 microg x mL(-1). Therefore, forscolin is rapidly excreted from liver microsomes. Attention should be paid to the drug interaction when forscolin was used along with other drugs metabolized by CYP3A4 in clinics.

Objective To explore the imaging characteristics of different sizes of MR small surface coil.Methods A water phantom with NiSO4· 6H2O for Siemens was scanned with 4 cm,7 cm and 11 cm small surface coils in Siemens 3.0 T MR system.T1WI,T2WI,three dimensional reversed fast imaging with steady state precession with diffusion-weighted(3D-PSIF-DWI) and three dimensional fast imaging with steady state precession and fat suppression(3D-FISP-FS) images were obtained.The imaging area,signal intensity (SI),standard deviation (SD) and signal-to-noise ratio (SNR) variations of different depths (from the near to the distant) were measured and compared.Curves according to the SI and SNR data were draw.SI and SNR characteristics of images obtained by L11 separately and used together with spine matrix coil were compared by using signed rank sum test.Results The signal intensity of images scanned by 4 cm,7 cm small surface coil decreased gradually in the depth of 0.2 to 2.2 cm,maintain good signal uniformity in the depth of 2.2 to 4.2 cm,and the signal intensity obtained by 11 cm coil maintain good signal uniformity in the depth of 5.2 cm.The optimum imaging widths of 4 cm,7 cm and 11 cm coil were about 7.0,8.5 and 11.0 cm.As the diameter of the coil increased,the imaging width and depth increased,but the received noise also increased.The SNR gradually reduced from the center to the edge of the coils.The imaging area increased but the local SNR decreased when using L11 coil combine with spine matrix coil,which showed a statistically significant difference (Z=-2.354,P=0.019).Conclusions A suitable size of small surface coil should be chosen according to the location and size of the organ or lesion before clinical MR examination.Other coils should be turned off to improve the SNR.

ObjectiveTo investigate the capacity and diagnostic value of various MRI seguences in patients with trigeminal neuralgia.Methods MR images of 60 patients with trigeminal neuralgia were analyzed retrospectively.The sensitivity,specificity and diagnostic value of various MRI sequences were evaluated comparing with clinical data and operation results.All patients were scanned with conventional sequences including SE-T1WI,T2WI,FLAIR of head.Among them,9 cases were injected with contrast agent,49 cases were scanned with 3D-TOF and 3D-TSE sequences on cerebellopontine angle additinally.The sensitivity,specificity and accuracy of the 3D-TOF and 3D-TSE sequences were analyzed by using the x2 test.Results Six cases with tumor,3 cases with radiculitis and meningitis,1 case with multiple sclerosis and 1 case with pons infarction were diagnosed by conventional MR sequences.MRI of 49 cases with 3D-TOF and 3D-TSE showed neurovascular compress proved by operation.The sensitivity,specificity and accuracy of 3D-TOF and 3D-TSE were 95.3％ (41/43)vs.95.6％ (43/45),66.7％ (4/6)vs.50.0％(2/4) and 91.8％ (45/49)vs.91.8％ (45/49),and no significantly difference was found between the two sequences (x2 =0.13,0.19 and 0.17,P ＞0.5).ConclusionsMRI plays an important role in displaying the causes and diagnosis of trigeminal neuralgia.The conventional head MR sequences should be recommended for diagnosis of secondary TN caused by tumor and inflammation et al,and further 3D-TOF and 3D-TSE with high sensitivity and accuracy should be applied in patients with primary TN to display the neurovascular relationship.

Abstract: This study is to elucidate the metabolic pathway of 1,2-[bis (1,2-benzisoselenazolone-3 (2H)-ketone)]-ethane (BBSKE) in rats. Rats were administrated with a single dose of BBSKE 200 mg x kg(-1). The metabolites in rat urine, feces, bile and plasma were identified by LC-MSn analysis. The characterization of fragment ions from LC-MSn chromatography and mass spectrometry was applied to the investigation of structures of metabolites. Three phase I metabolites were detected in rat urine and feces. Two of them were also found in plasma and one existed in bile. These products were derived from oxidized, methylated and S-methylated BBSKE, separately. One phase II glucuronide of BBSKE was also found in bile. Therefore, it is possible that BBSKE was metabolized by oxidization, methylation and glucuronidation.

Objective To investigate the feasibility of the low tube voltage setting and personalized contrast agent application in 64-row multi-slice spiral CT pulmonary angiography.Methods Ninety patients with high risk of pulmonary artery embolism were sequentially enrolled in the study and divided into 3 groups employing completely randomized design: (1) Regular group included 30 patients using 120 kV and fixed dose of 70 ml contrast agent, (2)Another 30 patients were in 120 kV group, using 120 kV and the contrast amount was determined according to the patient weight (1.0 ml/kg), (3) The remaining 30 patients were included in 100 kV group, using 100 kV and the contrast amount was also determined according to the patient weight(1.0 ml/kg).Administration of contrast agent was completed within 20 seconds for all the patients, followed by 20 ml of saline.The objective and subjective indexes for assessing CT image quality, CT dose index volume (CTDIvol) and effective received dose (ERD) were compared between 120 kV group and 100 kV group; then the contrast media volume, injection rate, objective CT image indexes and subjective indexes for image quality was compared between the 100 kV group and regular group.The variance analysis and post hoc test were employed for the statistical analysis.Results Compared with 120 kV group(3.4± 0.7), the image quality of 100 kV group(5.2±1.8)had higher noise(52.9%), but subjective index for the image quality demonstrated no differences(q=0.272 ,P=0.063)in mediastinum window while CTDIvol and ERD decreased for 34.9%[(9.5±0.0) vs (14.6±0.0) mGy]and 36.8%[(3.8±0.6) vs (2.4± 0.4) mSv].The mean CT values on pulmonary artery of 100 kV group[(269.2±54.7) HU]were 13.4% (31.8/237.4) higher than the 120 kV group[(237.4±62.9) HU], but there was no statistical differences eornpared to normal group(q=0.172,P=0.260).Conclusion Using low kV setting (100 kV) to reduce radiation dose is proved to be effective and feasible in 64-MSCT pulmonary angiography.Personalized contrast agent injection has clinical application value for specific patient group.

Objective To develop a sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of forsklin in rat plasma.Methods After extraction with methyl tert-butyl ether,chromatographic separation was performed on a C18 column with the mobile phase consisting of water ( 0.1％ formic acid)-acetonitrile in a gradient elution mode.A tandem mass spectrometer equipped with electrospray ionization (ESI) source was used as detector in the positive ion mode.Quantification was performed using multiple reaction monitoring (MRM) with the precursor product combination ions of m/z 411→375.3 and 285→193 for forsklin and diazepam.Results Good linearity was obtained in the 0.5-1000 ng/ml range for the analyte and the analytical method was validated in terms of specificity,precision,accuracy,recovery,stability and matrix effect.These assays gave RSD values always lower than 14.4％ and RE values between -3.5 ％ and 3.8％.In addition,the specificity,extraction recovery,stability and matrix effect were satisfactory.Conclusion Due to its high sensitivity,specificity and simplicity,the method could be used for pharmacokinetic studies of forsklin.

Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of yogliptin and its metabolite in Wistar rat plasma. Linagliptin and dexamethasone were chosen as the internal standards of yogliptin and its metabolite, (R)-8-(3-hydroxypiperidine- -yl)-7-(but-2-yn-1-yl)-1-((5-fluorobenzo[d]thiazol-2-yl)methyl)-3-methyl- H-purine-2, 6 (3H, 7H)-dione, respectively. After a simple protein precipitation using acetonitrile as the precipitating solvent, both analytes and ISs were separated on a Grace Altima HP C18 column (2.1 mm x 50 mm, 5 microm) with gradient elution using methanol (containing 0.1% formic acid, 4 mmol x L(-1) ammonium acetate)-0.1% formic acid (containing 4 mmol x L(-1) ammonium acetate) as the mobile phase. A chromatographic total run time of 4.4 min was achieved. Mass spectrometric detection was conducted with electrospray ionization under positive-ion and multiple-reaction monitoring modes. Linear calibration curves for yogliptin and its metabolite were over the concentration range of 0.5 to 500 ng x mL(-1) with a lower limit of quantification of 0.5 ng x mL(-1). The intra- and inter- assay precisions were all below 14%, the accuracies were all in standard ranges. The method was used to determine the concentration of yogliptin and M1 in Wistar rat plasma after a single oral administration of yogliptin (27 mg x kg(-1)). The method was proved to be selective, sensitive and suitable for pharmacokinetic study of yogliptin and M1 in Wistar rat plasma.

Meridians in human body were classified as white meridian and black meridian according to Tibetan medicine.Season and environment,improper diet,toxic heat and trauma were recognized as main reasons damaging the white meridian in Tibetan Medicine,leading to the emerge of white meridian disease induced by Long (one of the three factors) and blood disorder.White meridian disease in Tibetan medicine involved a series diseases,such as many clinical diseases,due to the damage of white meridian system caused by pathogenic factors.Stroke also belonged to white meridian disease.Drugs and treatments were selected based on the nature of disease such as cold and heat,onset,thelocation of disease and the three factors (Chi Ba,Long and Pei Gen).It was the fundamental principle of the treatment rules of white meridian disease in Tibetan medicine,namely,prescribing medication with the rule of diagnosis and treatment,comprehensive analysis of the causes of diseases and mastering the change law of diseases and syndromes in clinic.