In order to explore the clinical hypolipidemic features of Daidai flavone extract, the pharmacokinetics features of characteristic active ingredients of Daidai flavone extract in normal and hyperlipemia rats were studied and compared. The study established the quantitative determination method of naringin and neohesperidin in plasma by UPLC-MS. Study compared the pharmacokinetics differences of naringin and noehesperidin in normal and hyperlipemia rats on the basis of establishment of hyperlipemia model. Results indicated that the pharmacokinetics features of characteristic active ingredients of Daidai flavone extract in normal and hyperlipemia rats showed significant differences. The C(max) of naringin and neohesperidin in hyperlipemia rats plasma after oral administration of Daidai flavone extract increased obviously, while t1/2, MRT and AUC0-24 h decreased, compared to normal rats. But t(max) showed no differences to that of normal rats. The results further proved Daidai flavone extract would have better hypolipidemic effect in the hyperlipemia pathological status. And the characteristic active ingredients naringin and noehesperidin were the material base of Daidai flavone extract to express the hypolipidemic effect.
Animals ; Citrus ; chemistry ; Drugs, Chinese Herbal ; isolation & purification ; pharmacokinetics ; Flavones ; chemistry ; Hyperlipidemias ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley

Adenocarcinoma ; drug therapy ; Antibodies, Monoclonal ; adverse effects ; Drug Resistance, Neoplasm ; Female ; Fever ; chemically induced ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; drug therapy ; Middle Aged ; Quinazolines ; therapeutic use

A large amount of nicotinamide adenine dinucleotide phosphate (NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells. Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool. ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis. In the present study, we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC) cells. High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells. However, there were no obvious changes in the other two pathways for glucose metabolism: glycolysis and oxidative phosphorylation. Interestingly, NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells, whereas no significant difference was observed under high-glucose condition. ME1-repressed cells had significantly decreased tolerance to low-glucose condition. Moreover, NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress. Furthermore, diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein. Collectively, these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.
Carcinoma ; Cell Line, Tumor ; Cell Movement ; Cell Survival ; Glucose ; metabolism ; Glycolysis ; Humans ; Malate Dehydrogenase ; metabolism ; NADP ; metabolism ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Invasiveness ; Oxidation-Reduction ; Oxidative Phosphorylation ; Pentose Phosphate Pathway ; Proto-Oncogene Proteins c-akt ; metabolism

OBJECTIVETo explore the changes of surface antigen and function of rituximab on dendritic cells derived from patients with Primary immune thrombocytopenia (ITP) to further understand the effective mechanism of immunotherapy.

METHODSThe peripheral blood mononuclear cells (PBMCs) were isolated from remission patients with ITP before and after low-dose rituximab infusion, and the PMNCs were stimulated for 5 days by rhGM-CSF and rhlL-4 in 5% CO2 air at 37°C incubator. Then all of DCs were cultured with TNF-α for 48 hours. The morphology of DCs was monitored under inverted microscope daily, and the surface antigens of the DCs were analysed by flow cytometry, meanwhile the levels of IL-12p70 and TGF-β1 in supernatants were detected by ELISA, mix lymphocyte reaction was performed by MTT assay.

RESULTS(1) Rituximab-treated-DCs showed no obvious tree-like protruding compared with untreated-DCs. The former cells were small and most of nucleus were centric. (2) The expressions of HLA-DR, CD80, CD83 and CD86 on rituximab-treated-DCs \[56.37 ± 3.95)%, (36.41 ± 2.82)%, (30.45 ± 4.61)% and (41.98 ± 4.17)%, respectively\] were significantly lower than those untreated-DCs \[(73.71 ± 7.61)%, (55.14 ± 7.30)%, (80.91 ± 7.09)% and (59.03 ± 3.43)%, respectively\](all P < 0.05), the concentration of IL-12p70 was significantly lower, \[(66.87 ± 4.29)% vs (50.17 ± 14.52)%\], while that of TGF-β1 \[(9.70 ± 0.31)%\] higher than the untreated-DCs \[(2.70 ± 0.36)%\] (P < 0.05). (3) The abilities to activate T cells proliferation of rituximab-treated-DCs reduced compared with untreated-DCs.

CONCLUSIONThe surface antigen of ITP-DCs and the concentration of IL-12p70 reduced after the low-dose rituximab infusion. The abilities to activate T cells proliferation reduced while the concentration of TGF-β1 increased. Rituximab may achieve its therapeutic effect on ITP by downregulating the immunoreactivity of DCs.

Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; therapeutic use ; Cell Proliferation ; Cells, Cultured ; Dendritic Cells ; cytology ; metabolism ; secretion ; Female ; Humans ; Interleukin-12 ; metabolism ; Lymphocyte Activation ; Male ; Rituximab ; T-Lymphocytes ; immunology ; Thrombocytopenia ; drug therapy ; immunology ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo study the osseointegration of the nanophase hydroxyapatite biograde-coated implants and host bone.

METHODSNanophase hydroxyapatite biograde-coated implants, hydroxyapatite biograde-coated implants and noncoated Ti-6Al-4V implants were inserted into both femoral of Beagle canines the tissue response, dynamic osteogensis and SEM were studied at 4, 8 and 12 weeks.

RESULTSThe degradation of nanophase hydroxyapatite was slower than hydroxyapatite, dynamic osteogensis and the form of osteoblast were better than the control groups.

CONCLUSIONThe biological reaction of Nanophase hydroxyapatite biograde-coated implants is better than hydroxyapatite coated implant.

Animals ; Bone Substitutes ; chemistry ; Coated Materials, Biocompatible ; chemistry ; Dogs ; Durapatite ; chemistry ; Male ; Materials Testing ; Nanoparticles ; Osseointegration ; physiology ; Surface Properties

Antigens, Viral ; genetics ; metabolism ; Cell Line ; Cell Phone ; Gene Expression Regulation, Viral ; radiation effects ; Herpesvirus 4, Human ; physiology ; radiation effects ; Humans ; Immunohistochemistry ; Viral Proteins ; genetics ; metabolism

The study established a UPLC-MS/MS method that is used for simultaneous determination nine major bioactive compounds of Dachengqi Tang in rat plasma. Using Aglient C18 column (2.1 mm x 50 mm,1.7 microm) was chromatographed, using methanol-5 mmol x L(-1) ammonium formate mobile phase gradient, elution 0.3 mL x min(-1). In the plasma pre-treatment process, not only the method of methanol and acetonitrile protein precipitation was investigated, and different factors extraction solvent, the type of the scroll time, the number and the type of extraction solvent, the extraction volume of the extraction solution of liquid-liquid extraction is investigated. Finally, with ibuprofen as an internal standard, using ethyl acetate liquid-liquid extraction method pretreatment blood, N2 dry reconstituted supernatant after centrifugation UPLC-MS/MS analysis, in electrospray ionization (ESI) negative mode, using multiple reaction monitoring mode for testing. The linear range of emodin, rhein, aloe-emodin, chrysophanol, magnolol, honokiol, hesperidin and hesperitin is 0.33-660, 0.40-792, 0.41-827, 0.34-680, 0.45-907, 0.46-927, 0.43-867, 0.34-683, 0.39-787 microg x L(-1) respectively, good linear relationship; and extraction recovery were greater than 69.39%, days after the day of the RSD is less than 15%. This method can be used to study the rat gastric large bearing gas after Dachengqi Tang, the simultaneous determination of nine components in plasma for its pharmacokinetics and efficacy material base to provide a theoretical basis.
Animals ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Female ; Male ; Plasma ; chemistry ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; methods

Objective To establish a sensitive and specific RP-HPLC method for determination caderofloxacin concentration in healthy human plasma. Methods Human plasma with internal standard was precipitated by perchloric acid. The separation was analyzed in gradient elution system and the detection wave was 286 nm. Results The linear range of pseudoephedrine was 0.1 ～ 10. 0 mg · L-1. The relative re-covery were within 96.41% ～ 109.52%. The within - day and the be-tween day RSD were all less than 15%. After single infusion cadero-floxacin of 400 mg/3 h in two healthy volunteers. It was found to be fit-ted to a two - compartment open model and its pharmacokinetic param-eters were as follows: Cmaxwas, 3.39, 4.04 mg·L-1, AUC0-t was 32.35,28.26 mg · h·L-1, t1/2β was 7.74,6.73 h, respectively.Conclusion The method is accurate, convenient, sensitive, specific,and was suitable for the study of clinical pharmacokinetics.

OBJECTIVETo investigate the clinical implications of reperfusion arrhythmias during primary percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI).

METHODSData from 228 AMI patients in whom the infarct-related artery (IRA) were successfully recanalized by primary PCI were retrospectively analyzed. The 228 patients were divided into 2 groups: myocardial ischemia-reperfusion injury (MIRI) group (n=119) in whom MIRI events occurred within minutes after successful recanalization of IRA, and non-MIRI group (n=109). The 119 patients in MIRI group were further divided into 3 subgroups: severe bradycardia with hypotension (brady-arrhythmia subgroup), lethal ventricular arrhythmias requiring electrical cardioversion (tachy-arrhythmia subgroup), and IRA antegrade flow less than or equal to TIMI 2 grade without angiographic evidence of abrupt closure (no-reflow subgroup).

RESULTS(1) Clinical and angiographic data: Compared with non-MIRI group, MIRI group was characterized by more inferior infarct location, shorter ischemic duration, more frequently right coronary artery as IRA, more diseased vessels, more often TIMI 0 grade of initial antegrade flow in IRA, less pre-infarction angina, more renal insufficiency, and higher in-hospital mortality (13.4% vs. 4.6%, P=0.021). (2) The peak CK level was remarkably lower in brady-arrhythmia subgroup than that in non-MIRI group (2010 IU/L vs. 2521 IU/L, P=0.039). The peak CK or CK-MB level was notably higher in no-reflow subgroup than in non-MIRI group (4573 IU/L, 338 IU/L, respectively, P=0.000). (3) Left ventricular ejection fraction in no-reflow subgroup was significantly lower than in non-MIRI group (38.7% +/- 8.3% vs. 51.2% +/- 8.1%, P=0.000), left ventricular end-diastolic volume in no-reflow subgroup was greater than that in tachy-arrhythmia subgroup [(135 +/- 32) ml vs. (105 +/- 19) ml, P=0.029].

CONCLUSIONReperfusion arrhythmias may imply the existence of much survived myocardium and do not enhance myocardial damage, while no-reflow increases myocardial injury and induces permanent impairment of cardiac function.

Arrhythmias, Cardiac ; complications ; Cell Survival ; Humans ; Myocardial Infarction ; therapy ; Myocardial Reperfusion ; Myocardial Reperfusion Injury ; etiology ; Myocardium ; enzymology ; Retrospective Studies