Objective To study the protection and mechanism of co-administration of vitamin E with coenzyme Q10(CoQ10) to valproate-associated hepatotoxicity in infantal rats.Methods The rat models were established by oral administration of valproic acid(VPA) in ablactation(21 days) Wistar rats,at doses of 500 mg/(kg?d) during 30 days,other groups received the same amount of VPA with phemobarbitone(PB) and co-administration with vitamin E and CoQ10.The changes of liver cell morphology and the blood coagulation test,as well as the contents of succinic dehydrogenase(SDH),cytochrome oxidase(CCO),cytochrome,the levels of glutothione(GSH) and malondial dehyde(MDA) in rat liver mitochondria were detected by chromatometry,HPLC,Oil-Red-O staining and electron microscope,respectively.Results 1.Average content of cytochrome aa3 in liver mitochondria of infantal rats were reduced by 58.80% and(61.80%) because of administration of VPA and VPA added with PB.The protection against the loss of cytochrome aa3 by coadministration of VitE and CoQ10 was obvious.As for activities of SDH and CCO,which affected by VPA and VPA added with PB in rats,were significantly lowered compared with control group(P

Background Hypertension,ischemia and hypoxia induce the increase of glutamate level in eye tissue and furthermore produce excitatory damage and apoptosis of retinal ganglion cells(RGCs).At present,the study on the protection of traditional Chinese medicine on glutamate-induced retinal excitatory damage is lack.objective Present study was to explore the protective effects of Huoxue huayu decoction,a Chinese herbal recipe,on RGCs in acute ocular hypertension model. Methods Fony-five healthy clean Wistar rats were divided into three groups randomly.The acute ocular hypertension models were established in 40 Wistar rats by injecting the normal saline solution into the anterior chamber to elevate the intraocular pressure for 60 minutes.Huoxue huayu decoction of 4 ml was administered intragastrically once per day in 20 model rats.Other matched 5 normal Wistar rats served as normal control group.The rats were sacrificed on 1,3,7 and 14 days after modeling and the retinas were isolated for the histopathologieal and uhrastructure examination.Expression of glutamate transporter in the retina of acute ocular hypertension and normal rat retina were detected using quantitative real-time polymerase chain reaction.The utilization of animals followed the Association for Research in vision and Ophthalmology. Results After acute ocular hypertension.the retina thickness attenuated and the numbers of RGCs decreased under the light microscope in 1,3,7 and 14 days after modeling in comparison with normal control rats.The degradation of the organelle and edema as well as changes of cell nuclei were seen in model rats under the transmission electron microscopy.The expression of glutamate transporter mRNA in model group and glutamate transporter group was rapidly elevated in the first day (P<0.05),descended at the third days(P<0.01)and returned to the normal level 7 days later(P>0.05).Conclusion Huoxue huayu decoction can protect the retina against RGCs damage in the acute ocular hypertension by elevating the expression of glutamate transporters in retina.

The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.
Administration, Oral ; Adolescent ; Adult ; Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Antihypertensive Agents ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; Cross-Over Studies ; Drug Liberation ; Humans ; Hydrochlorothiazide ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Male ; Tablets ; Tandem Mass Spectrometry ; Therapeutic Equivalency ; Valsartan ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Young Adult

A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.
Administration, Oral ; Area Under Curve ; Asian Continental Ancestry Group ; Chromatography, Liquid ; Cyclohexanols ; blood ; pharmacokinetics ; Delayed-Action Preparations ; Desvenlafaxine Succinate ; Dose-Response Relationship, Drug ; Healthy Volunteers ; Humans ; Male ; Plasma ; chemistry ; Stereoisomerism ; Tablets ; Tandem Mass Spectrometry

AIM:To investigate whether Smad pathway participates the process of extracellular signal regulated kinase (ERK) induced the proliferation of vascular smooth muscle cells (VSMCs). METHODS: Human umbilical artery smooth muscle cells (hUASMCs) were divided into four groups: control group, PDGF (platelet derived growth factor) group, ERK blocking agent group and PDGF+ERK blocking agent group. MTT assay was used to detect the proliferation of hUASMCs (A value). Immunohistochemical technique was used to detect the expression of PCNA, phosphorylated ERK (p-ERK) and phosphorylated Smad2/3 (p-Smad2/3) protein in hUASMCs. The expression of Smad2/3 mRNA in hUASMCs was detected by RT-PCR. RESULTS: The proliferation of hUASMCs and the expression of PCNA, p-ERK and p-Smad2/3 proteins in hUASMCs in PDGF group were increased obviously than those in other groups (P

Objective To investigate the characteristic and clinical significance of airway inflammation in children with acute asth-ma. Methods Underwent sputum induction and sputum induction in children (n=34) with acute asthma was repented in recovered children ( n = 24).Induced sputum were also taken from 15 healthy children as controls.Total and differential cell counts were per-formed. Interleukin(IL)-8、IL-6 were measured,The relationship between inflammatory cells and IL-8、 IL-6、peak expiratory (PEF) were analyzed.Results The inflammatory cell infiltrate was mixed including eosmophilic granulocytes, neutrophils, and macrophages. They decreased significantly, but eosinophilic granulocyte remained a higher percentage compared with healthy subjects. There was low-er percentage of lymphocytes at acute exacerhation.Eosinophilic granulocytes were correlated with the degree of airflow obstruction. Levels of IL-8、IL-6 were elevated during the acute exacerbation and decreased at resolution.IL-8 was correlated significantly with neutrophils at acute exacerhation and resolution.IL-6 was correlated signifficantly with eosinophilic granulocytes at acute exacerbation. Conclusions Airway inflammation is chataeterized by infiltration of eosinophils, neutrophils and macrophages.IL-8、IL-6 possibly is the important cytokines of airway inflammation in children with acute asthma. Increased eosinophils in induced sputum correlates with asthma severity. Therapy to the cytokines may have potential values.J Appl Clin pediatr,2004,19(12): 1023-1025

Objective To establish a RP-HPLC method for determining indigo and indirubin in Baphicacanthus cusia from different producing areas and medicinal parts. Methods The separation was achieved by an Agilent TC-C18 Column (4.6 mm×250 mm, 5 μm) at 25 ℃ using methanol-water (75??25) as mobile phase at a flow rate of 1 mL??min-1.The detection wavelength was 290 nm. Results Indigo had a good linear relationship with peak area at range of 0. 051 3-0.820 8 μg (r=0.999 3).The recovery rate was 99.00% and RSD was 1.30% (n=6).Indirubin had a good linear relationship with peak area at range of 0.049 5-0.792 0 μg (r=0.999 9).The recovery rate was 98.88% and RSD was 1.51% (n=6). Conclusion The contents of the two components are obviously different in Baphicacanthus cusia because of different places or medicinal parts. The proposed method is simple, rapid and reliable. This method for determination of indigo and indirubin in Baphicacanthus cusia by RP-HPLC provides a basis for quality control of Baphicacanthus cusia.

To study the metabolite excretion of theophylline, a rapid and specific method by liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) method for simultaneous determination of theophylline, 1, 3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX) and 1-methyluric acid (1-MU) in human urine was developed using theophylline-d6 and 5-fluorouracil as internal standards. Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the negative mode for mass spectrometric detection. After diluted with methanol and centrifuged, the analytes and ISs were separated on a XDB-Phenyl (150 mm x 4.6 mm, 5 microm) column with a mixture of water-methanol-formic acid (30 : 70 : 0.15) as mobile phase at a flow rate of 0.6 mL x min(-1). The linear calibration curves for theophylline, 1, 3-DMU, 3-MX and 1-MU were obtained in the concentration range of 1.0-250 microg x mL(-1), separately. The method herein described is effective and convenient, and can be used for determination of theophylline and its three metabolites. The results showed that urinary excretion ratio of theophylline, 1,3-DMU, 3-MX and 1-MU is approximately 1 : 3 : 1 : 2 in Chinese subjects, which is similar to the reported excretion pattern in Caucasian.
Administration, Oral ; Asian Continental Ancestry Group ; Calibration ; Chromatography, Liquid ; Delayed-Action Preparations ; metabolism ; Healthy Volunteers ; Humans ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Tandem Mass Spectrometry ; Theophylline ; metabolism ; urine ; Uric Acid ; analogs & derivatives ; urine ; Xanthines ; urine

Objective To explore the ideal treatment mode of brain metastases by Meta-analysis.Methods Articles were searched for from the databases at home and abroad using English and Chinese keywords.Searching time limited from the databases setting up to December 30,2012.Jadad score was applied to evaluate the qualities of literatures.RevMan5.0 software was applied to perform the Meta-analysis.A totle of 25 articles including 2 750 patients were eligible for the Meta-analysis,which divided into groups with different treatment.Results Compared with monotherapy,combined therapy improved 1-year survival (OR =0.58,95％ CI:0.46 ～0.71,P ＜0.000 01).In combined therapy groups,compared with two methods,three kinds of therapies improved 1-year survival (OR =0.63,95 ％ CI:0.50 ～ 0.80,P =0.000 1).Compared with local therapy only or systemic therapy only,systemic combined local therapy improved 1-year survival (OR =0.68,95％ CI:0.53 ～ 0.86,P =0.001 ; OR =0.59,95％ CI:0.41 ～ 0.86,P =0.006).In systemic combined local therapy groups,three kinds of treatments improved 1-year survival compared with two methods (OR =0.52,95％ CI:0.35 ～ 0.78,P =0.002).Compared with non-molecular targeted therapy,molecular targeted therapy improved 1-year survival (OR =0.76,95％ CI:0.67 ～ 0.87,P ＜ 0.000 1).Conclusion The reasonable treatment for patients with brain metastases is combined treatment with operation,radiotherapy and chemotherapy.There is better curative effect added molecular targeted therapy based on original scheme,if patients have targeted therapy indications.