The incompatibility of traditional Chinese medicines is related to the clinical medication safety, so has attracted wide attentions from the public. With the deepening of studies on the incompatibility of traditional Chinese medicines represented by 18 incompatible herbs, the incompatibility of theory traditional Chinese medicines has raised to new heights. From the origin of incompatibility theory of traditional Chinese medicines, relationship of herbs, harms of incompatible herbs and principle of prevention to toxic effects of specific incompatible medicines, the innovation and development of the traditional Chinese medicine incompatibility theory was explored. Structurally, the incompatibility of traditional Chinese medicines refers to the opposition of two herbs based on seven emotions and clinical experience. The combination of incompatible herbs may lead to human harms, especially latent harm and inefficacy of intervention medicines. The avoidance of the combination of incompatible herbs and the consideration of both symptoms and drug efficacy are the basic method to prevent adverse reactions. The recent studies have revealed five characteristics of incompatible herbs. Toxicity potentiation, toxication, efficacy reduction and inefficacy are the four manifestations of the incompatible relations. The material changes can reflect the effects of toxicity potentiation and toxication of opposite herbs. The accumulation of toxicity and metabolic changes are the basis for latent harms. The antagonistic effect of main efficacies and the coexistence of positive and negative effects are the distinctive part of the incompatibility. The connotation of incompatible herbs plays an important role in the innovation of the traditional Chinese medicine incompatibility theory.
Drug Incompatibility ; Drug Therapy ; history ; Drugs, Chinese Herbal ; chemistry ; history ; pharmacology ; History, Ancient ; Humans ; Medicine in Literature ; Medicine, Chinese Traditional

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of transformed hematopoietic progenitor cells. In order to investigate the role of sphingosine kinase-1 (SphK-1)/sphingosine 1-phosphate (S1P) signal pathway in the expression of CML cells, and to explore whether P210(bcr/abl) involved is activating SphK-1/S1P signal pathwey, the expressions of SphK-1 and S1P receptor mRNA in bcr/abl positive K562 cells and bcr/abl positive primary CML cells were detected by RT-PCR, the imatinib mesylate, the specific inhibitor of P210(bcr/abl) was employed to inhibit the P210(bcr/abl) tyrosine kinases of K562 cells and CML primary cells, and then the intracellular SphK-1 activity was assayed. The results indicated that after being cultured with 2.5 micromol/L imatinib mesylate for 0.5, 2, 6, 24 and 48 hours, the intensions of inhibiting SphK-1 activity were 0.007%, 38.9%, 34.6%, 28.1% and 76.1% resepectively. SphK-1 activity in CML cells also was reduced by 2.5 micromol/L imatinib mesylate (16.8% - 41.9% decrease). It is concluded that the CML cells express SphK-1 and different S1P receptor, and P210(bcr/abl) fusion protein in CML cells can activate SphK-1.
Benzamides ; Fusion Proteins, bcr-abl ; genetics ; metabolism ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; metabolism ; Lysophospholipids ; genetics ; metabolism ; Phosphotransferases (Alcohol Group Acceptor) ; genetics ; metabolism ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Signal Transduction ; genetics ; Sphingosine ; analogs & derivatives ; genetics ; metabolism

A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of budesonide in dog plasma. Budesonide and the internal standard triamcinolone acetonide were separated from plasma by alkalinized liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a Capcell Pak C18 MG column with the mobile phase consisted of acetonitrile -5 mmol x L(-1) ammonium acetate (60:40, v/v) at a flow-rate of 0.50 mL x min(-1). A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the negative ion mode. Quantification was performed using multiple reaction monitoring (MRM) of the transitions m/z 489 --> m/z 357 and m/z 493 --> m/z 413 for budesonide and the internal standard, respectively. The linear calibration curves were obtained in the concentration range of 25.0-2000 pg x mL(-1). The lower limit of quantification was 25.0 pg x mL(-1). The intra- and inter-day relative standard deviation over the entire concentration range was less than 15%. The accuracy was in the range of -8.1% to -1.7% in terms of relative error. The method was applied to a pharmacokinetic study of budesonide controlled-release capsules in Beagle dogs. Maximal budesonide plasma level was observed after (3.5 +/- 3.3) h and the Cmax was (786 +/- 498) pg x mL(-1) after a single oral administration of 9 mg budesonide capsules, Cmax was increased to (2142 +/- 1515) pg x mL(-1) after multiple oral administration (9 mg x 5 d) of budesonide capsules. This method was selective and rapid, and the sensitivity was sufficient for the purpose of the pharmacokinetic study of budesonide controlled-release formulation.
Animals ; Anti-Inflammatory Agents ; blood ; pharmacokinetics ; Area Under Curve ; Budesonide ; blood ; pharmacokinetics ; Chromatography, Liquid ; methods ; Delayed-Action Preparations ; Dogs ; Male ; Sensitivity and Specificity ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry ; methods

The aim of this research was to understand the influence of rhG-CSF on the sphingosine kinase (SphK) activity of monocytes. The peripheral blood monocytes were collected from 6 peripheral blood progenitor cell donors on the fifth day of mobilization with rhG-CSF and from 5 blood donors' buffy coats. The mRNA expressions of monocyte G-CSF receptor and SphK were tested with RT-PCR. The changes of SphK activity of monocytes were assayed after being treated with rhG-CSF. The results showed that the two kinds monocytes collected from both blood donors and peripheral blood progenitor cell donors mobilized with rhG-CSF expressed mRNA of G-CSF receptor and SphK. The SphK activity of monocytes collected from blood donors was not changed significantly after being treated with rhG-CSF (P > 0.05). The SphK activity of monocytes collected from peripheral blood progenitor cell donors transiently increased by (39.6 - 87.2)% after being treated by means of rhG-CSF (P < 0.05) without obviously dose-dependent effect. It is concluded that the SphK activity of monocytes collected from peripheral blood progenitor cell donors can be activated by rhG-CSF.
Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoietic Stem Cell Mobilization ; Humans ; Monocytes ; cytology ; enzymology ; Phosphotransferases (Alcohol Group Acceptor) ; drug effects ; metabolism ; Receptors, Granulocyte Colony-Stimulating Factor ; biosynthesis ; genetics ; Recombinant Proteins

To analyze naringin, naringenin and its metabolites in rat urine and feces after intragastric administration of alcohol extract of Exocarpium Citri Grandis, healthy SD rats were fed with alcohol extract of Exocarpium Citri Grandis for 3 days. On the last day, 0-24 h feces and 0-4 h, 4-8 h, 8-24 h urine were collected and analyzed by UPLC-Q-TOF/MS. The post-acquisition data were processed using Metabolynx The result is that naringin and its 6 metabolites, naringenin and its 4 metabolites were detected in the urine of rat. Meanwhile, naringin and its 3 metabolites, naringenin and its 2 metabolites were detected in the feces of rat.
Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; Citrus ; chemistry ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; Feces ; chemistry ; Flavanones ; metabolism ; urine ; Male ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

AIMTo identify the main metabolites of aconitine in the urine of rabbits.

METHODSAfter oral administration of aconitine (5 mg.kg-1), the urine of male rabbits was collected and extracted by solid phase extraction and analyzed by liquid chromatography-ion trap mass spectrometry.

RESULTSAconitine and 4 metabolites were found in the rabbit urine. Their protonated molecular ions at m/z 632, m/z 604, m/z 590, m/z 500 and multistage fragment ions with neutral loss of 60 u, 32 u, 28 u and 18 u were monitored. Their relative concentration were M1 > Aconitine > M4 > M2 > M3.

CONCLUSIONThe metabolites M1-M4 were deduced as 16-O-demethylaconitine, benzoylaconine, 16-O-demethylbenzoylaconine and aconine, respectively.

Aconitine ; analogs & derivatives ; metabolism ; urine ; Alkaloids ; urine ; Animals ; Chromatography, High Pressure Liquid ; Male ; Rabbits ; Spectrometry, Mass, Electrospray Ionization

The study was to understand the impact on the proliferation and cytotoxicity of donor's T cells during mobilization with rhG-CSF. The peripheral blood mononuclear cells (PBMNC) were collected from 15 donors before mobilization and on fifth day of mobilization with rhG-CSF. After the PBMNC were activated with 500 ng/ml of CD3 monoclonal antibody and 500 microg/ml of rhIL-2 for 96 hours, the activated T cells were collected for testing proliferation, cytotoxicity, Fas expression, perforin and Fas ligand (FasL) mRNA expression, the IFN-gamma concentration in the culture medium of the activated T cells was determined by radioimmunoassay. The results showed that the proliferation activity of T lymphocytes and the cytotoxicity of T cells activated with CD3 monoclonal antibody and rhIL-2 were reduced markedly after mobilization with rhG-CSF (P < 0.05). The Fas molecule expression in the activated T cells was very high both before and after mobilization with rhG-CSF (P > 0.10). The activated T cells expressed perforin mRNA and didn't express FasL mRNA both before and after mobilization with rhG-CSF. The concentration of IFN-gamma in the culture medium of the activated T cells decreased significantly after mobilization with rhG-CSF (P < 0.01). It is concluded that activity of proliferation and cytotoxicity of donor's T cells is impaired after mobilization with rhG-CSF.
Adolescent ; Adult ; Cell Proliferation ; drug effects ; Cells, Cultured ; Fas Ligand Protein ; biosynthesis ; genetics ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; administration & dosage ; pharmacology ; Hematopoietic Stem Cell Mobilization ; methods ; Humans ; Male ; Middle Aged ; RNA, Messenger ; biosynthesis ; genetics ; Recombinant Proteins ; T-Lymphocytes ; cytology ; drug effects ; T-Lymphocytes, Cytotoxic ; drug effects ; immunology ; fas Receptor ; biosynthesis ; genetics

Along with progress of modern science and technology, human is utilizing natural resources and their inherent law more effectively and more efficiently according to their own purposes. Chinese medicine pair (CMP) is relatively fixed combination of two TCMs which was proven to be effective in clinical application. CMP has its inner specification, and it is an intermediate point between single herb and many TCM formulae. With the aid of modern science and technology, and by means of choosing appropriate strategies and approaches, the compatibility rules of CMP might be revealed, which will be significant to develop the compatibility theory of TCM formulae and create modern TCM new drugs.
Animals ; Clinical Trials as Topic ; Drug Interactions ; Humans ; Medicine, Chinese Traditional ; methods ; Research Design ; Systems Biology

The metabolic effect of Fo-Shou-San on blood deficiency mice was studied by using metabolomic method. UPLC-QTOF/MS was used to analyze the plasma metabolome in blood deficiency mice. MS data were processed by MarkerLynx software. With multivariate statistical analysis of plasma metabolite profiles, a clear separation among control, blood deficiency model, and Fo-Shou-San groups was achieved. Potential biomarkers were selected according to the parameters of variable importance in the projection (VIP) and identified according to MS information and database retrieval. The metabolic network of blood deficiency was predicted via MetPA database. Twenty-two potential biomarkers were identified and used to explain the thiamine metabolism, arachidonic acid metabolism, sphingolipid metabolism, glyoxylate and dicarboxylate metabolism, histidine metabolism, nicotinate and nicotinamide metabolism, cysteine and methionine metabolism, tryptophan metabolism, starch and sucrose metabolism, tyrosine metabolism and citrate cycle (TCA cycle). Those metabolic pathways were disturbed in blood deficiency mice, but which could be regulated nearly to normal state after Fo-Shou-San administration. In this study, the metabolomics of blood deficiency mice and the action mechanism of nourishing blood effect of Fo-Shou-San were evaluated. The physiological and metabolic state of the organism could be represented comprehensively by using metabolomics. And metabolomics can be used to evaluate the pharmacodynamics and related mechanisms of Chinese medicine and formulae.
Animals ; Arachidonic Acid ; metabolism ; Biomarkers ; blood ; Blood Coagulation Disorders ; blood ; metabolism ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; pharmacology ; Female ; Metabolic Networks and Pathways ; drug effects ; Metabolome ; Metabolomics ; Mice ; Mice, Inbred ICR ; Plasma ; metabolism ; Random Allocation ; Spectrometry, Mass, Electrospray Ionization ; Sphingolipids ; metabolism ; Thiamine ; metabolism

BACKGROUNDDoppler color echocardiography is a common method for detecting coronary artery lesions in patients with Kawasaki disease (KD). However, the diagnostic accuracy for the whole coronary artery lesions is limited. The purpose of this study was to compare the diagnostic value of dual-source computed tomography (DSCT) and Doppler color echocardiography for the assessment of coronary artery lesions caused by KD.

METHODSSixteen patients, 12 with typical KD and 4 with atypical KD, underwent DSCT and Doppler color echocardiography. The position and internal diameter of each coronary artery lesion was measured. Correlation analysis was used to compare the diagnostic value of the two imaging modalities.

RESULTSIn the typical KD group, seven patients did not have any coronary artery lesion as confirmed by both DSCT scans and Doppler color echocardiography; in four patients proximal coronary artery injuries were identified by both modalities; in one patient an aneurysm in the middle and distal segments of the coronary artery was detected by DSCT but was negative in Doppler color echocardiography. In the atypical KD group, three cases showed the same results with both modalities, while one case with coronary artery stenosis in the middle segment was identified by DSCT but not detected by Doppler color echocardiography. There was a good correlation between the two imaging modalities (Kappa value, 0.768 (>or= 0.75)).

CONCLUSIONDSCT coronary artery angiography is an accurate, non-invasive, and valuable technique for detecting and following up coronary artery lesions in patients with KD.

Adolescent ; Child ; Child, Preschool ; Coronary Angiography ; methods ; Coronary Artery Disease ; diagnostic imaging ; Echocardiography, Doppler, Color ; Female ; Humans ; Infant ; Male ; Mucocutaneous Lymph Node Syndrome ; complications ; diagnostic imaging ; Tomography, X-Ray Computed ; methods