Deflazacort (DFZ, a prodrug) is well absorbed and rapidly metabolized into the active metabolite 21-hydroxydeflazacort (21-OH DFZ) after oral administration. The aim of this study is to evaluate the pharmacokinetic properties of 21-OH DFZ in healthy Chinese volunteers after a single and multiple oral administration of DFZ tablets under fed condition. Twelve volunteers (six males and six females) were administered a single dose of 6 mg or 12 mg or 24 mg of DFZ in three different periods separately, according to the 3 x 3 Latin square design. Between each administration period there was a washout period of one week. The multiple-dose study of 12 mg dose DFZ per day for 7 consecutive days was started after a 1 w washout period when the single-dose study completed. The pharmacokinetic parameters of 21-OH DFZ after the single oral administration of 6 mg, 12 mg and 24 mg DFZ tablets were as follows: (37.7 +/- 11.6), (61.5 +/- 17.7) and (123 +/- 23) ng x mL(-1) for C(max); (1.90 +/- 0.32), (1.96 +/- 0.27) and (2.13 +/- 0.34) h for t1/2; (96.6 +/- 25.9), (190 +/- 44) and (422 +/- 107) ng x h x mL(-1) for AUC(0-14 h), respectively. After the multiple dose administration, the mean plasma concentration at steady-state C(av) was (7.00 +/- 1.66) ng x mL(-1) and the degree of plasma concentration fluctuation DF was 7.7 +/- 1.2. The results showed that the pharmacokinetic characteristics of 21-OH DFZ in healthy Chinese volunteers were linear over the dose range of 6 to 24 mg. No significant gender differences were found in the pharmacokinetics of 21-OH DFZ in healthy Chinese volunteers. After the multiple dose administration of 12 mg DFZ for 7 d, no accumulation of 21-OH DFZ in healthy Chinese volunteers was observed.
Administration, Oral ; Area Under Curve ; Asian Continental Ancestry Group ; Female ; Healthy Volunteers ; Humans ; Male ; Pregnenediones ; pharmacokinetics ; Tablets

Objective:To explore the application of model-based systems engineering (MBSE) in process design of management business of medical college and relevantly concrete practice.Methods:This research proposed a modeling method of MBSE to be used in Cameo Systems Modeler platform, and used systems modeling language (SysML) to complete the construction of simulating business environment of management business of medical college.And the business process of applying internet account was used as sample to construct activity graph of black box by adopting SysML.Through captured derivative demands to explore and construct activity graph of white box that based on SysML, and complete decoupling for the department of business process.At last, this research observed lane situation of user, and determined the relevant requirement and updated the design of business process.Results:The construction for top-level environment of business management in business process of medical college management has been completed.And a business process was chosen to implement optimization, and its results indicated the business that once need be completed in 3 times that included college, information center and finance office could be shortened to integrate directly entering information of new user, uploading identify card photography, completing check and opening account at backstage of information center and transferring account at backstage of finance office into completion at 1 time after the process was optimized.Conclusion:The modeling system of MBSE can meet the needs of sorting coupling business of medical college, and enhance design efficiency of system, and decrease iteration times of business process of users.

Simvastatin is a hypolipidemic drug that inhibits hydroxymethylglutaryl coenzyme A (HMGCoA) reductase to control elevated cholesterol,or hypercholesterolemia.Previous studies have shown that simvastatin may attenuate inflammation in ischemia-reperfusion injury and sepsis.Herein,we hypothesized that simvastatin may prevent rats from lipopolysaccharide (LPS)-induced septic shock.In our study,rats were divided into a saline group,an LPS group and an LPS plus simvastatin group.Male Sprague-Dawley (SD) rats were pretreated with simvastatin (1 mg/kg) for 30 min before the addition of LPS (8 mg/kg),with variations in left ventricular pressure recorded throughout.Ninety min after LPS injection,whole blood was collected from the inferior vena cava,and neutrophils were separated from the whole blood using separating medium.The neutrophils were then lysed for Western blotting to detect the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1).In addition,mesentery microcirculations of inlet diameter,outlet diameter and blood flow rate were measured in all three groups.The results indicated that simvastatin significantly promoted heart systolic function and increased the level ofuPA while simultaneously inhibited the expression of PAI-1 as compared with LPS group.Moreover,simvastatin reversed the LPS-induced inhibition of mesentery microcirculation.Taken together,it was suggested that simvastatin can effectively protect the rats from LPS-induced septic shock.

The study is to develop a method to determine 3 batches leaves of Nauclea officinalis and stems of N. officinalis by HPLC. The differences between strictosamide contents and fingerprints was compared, then chromatographic peak of fingerprints was validated with the assistance of LC-MS. The strictosamide contents in stems of N. officinalis were higher than leaves of N. officinalis. The main chemical composition in leaves of N. officinalis and stems of N. officinalis were alkaloid which revealed by LC-MS. There are 7 chemical compositions were same between them, but the chemical composition in leaves of N. officinalis is more than stems of N. officinalis. This provides a scientific basis for the development of the potential medicinal value of leaves of N. officinalis and the sustainable utilization of N. officinalis.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Molecular Structure ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Rubiaceae ; chemistry ; Spectrometry, Mass, Electrospray Ionization

A reasonable method for the quality control of tablets of Ginkgo biloba leaves was established in this paper. The total flavonol glycosides and terpene lactones of G. biloba tablets were quantified by HPLC. Totally, 16 batches of the commercially available tablets of G. biloba leaves were determined. Among of them, 2 batches were unqualified in the content of total flavonol glycosides, and 3 batches were unqualified in the content of terpene lactones. A validated HPLC fingerprint method was established to evaluate the commercially available tablets of G. biloba leaves with the assistance of LC-MS. Sixteen batches showed the similarity of 0.763-0.989. There were 31 fingerprint chromatogram peaks were identified as flavonoids compositions by LC-MS. This provides a research idea for the quality control of tablets of G. biloba leaves.
Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; chemistry ; Ginkgo biloba ; chemistry ; Mass Spectrometry ; methods ; Plant Leaves ; chemistry ; Quality Control ; Tablets ; chemistry

OBJECTIVETo investigate the effects of estrogen receptor alpha (ERa) and insulin-like growth factor 1 (IGF1) on the proliferation of prostatic smooth muscle cells (PSMCs) in vitro.

METHODSThe ERalpha shRNA expression frame was subcloned to the pGSadeno adenovirus vector by homologous recombination technology to construct the pGSaaeno-ERalpha vector. After the mouse PSMCs were transfected in vitro by pGSaaeno-ERalpha, the mRNA and protein expression levels of ERalpha were detected by RT-PCR and Western blot respectively. The expression of IGF1 in the ERa-reduced cells was determined by Western blot 6 hours after treatment with 17beta-estradiol (E2) at 10(-8) mol/L. The post-transfection activity of estrogen or exogenous IGF1 in the proliferation of PSMCs was evaluated by MTT chlormetric analysis.

RESULTSAfter treatment with E2, the proliferation of PSMCs and the expression of the IGF1 gene were significantly increased in the normal control group (P <0.05), but not obviously changed in the ERalpha-siRNA group (P> 0.05). And exogenous IGF1 failed to induce the proliferation of the ERalpha-reduced PSMCs.

CONCLUSIONE2 induces the expression of IGF1 via ERalpha, and IGFl, with the interaction of ERalpha, promotes the proliferation of PSMCs.

Animals ; Cell Proliferation ; Cells, Cultured ; Estradiol ; pharmacology ; Estrogen Receptor alpha ; metabolism ; Insulin-Like Growth Factor I ; metabolism ; Male ; Mice ; Myocytes, Smooth Muscle ; cytology ; Prostate ; cytology ; RNA, Messenger ; genetics

OBJECTIVEThe purpose of this study was to observe the association between inflammation status/autoimmune antibodies and plasma lipid in patients with rheumatoid arthritis (RA).

METHODSA total of 402 RA patients were admitted into our hospital during January 2008 to March 2009 and 225 RA patients who met the inclusion criteria were selected to perform a full lipid profile examination including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), anti-keratin antibody (AKA), anti-perinuclear factor autoantibody (APF) and complement (C) were also evaluated. Atherogenic index of plasma (AIP) was calculate by the formula Log (TG/HDL-C).

RESULTS(1) There were 12.9%, 10.2% and 14.2% patients with elevated TC, LDL-C and TC respectively, patients with reduced HDL-C accounted for 43.6%. (2) C(3) was higher in elevated TC group than normal TC group (P < 0.05). ESR and CRP were significantly higher in decreased HDL-C group than in normal HDL-C group (P < 0.05). CRP, C(3) and C(4) were significantly higher in elevated LDL-C group than in normal LDL-C group (P < 0.05). (3) Multiple stepwise regression analysis showed that C(3) was positively correlated with TC (R(2) = 0.067, P < 0.05). Both ESR and CRP were negative correlated with HDL-C (R(2) = 0.202, P < 0.05). CRP and anti-CCP were positively correlated with LDL-C (R(2) = 0.129, P < 0.05). ESR and C(4) were positively correlated with AIP (R(2) = 0.046, P < 0.05).

CONCLUSIONThis study showed that rheumatoid arthritis is associated with an abnormal lipid profile, especially in patients with increased inflammation markers and autoimmune antibodies. Moreover, ESR and C(4) were predictors of increased AIP in this cohort.

Aged ; Arthritis, Rheumatoid ; blood ; immunology ; physiopathology ; Autoantibodies ; blood ; Autoimmunity ; C-Reactive Protein ; analysis ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Complement System Proteins ; Humans ; Inflammation ; Lipids ; blood ; Lipoproteins, HDL ; blood ; Triglycerides ; blood

OBJECTIVETo investigate the efficacy and toxicity of methotrexate (MTX) give intravenously in the primary treatment of gestational trophoblastic tumor (GTT).

METHODSA total of 37 patients with low-risk GTT was primarily treated by single MTX in Women's Hospital, School of Medicine, Zhejiang University. Data on the patients' age, clinical stage, WHO classification criteria, antecedent pregnancy, presenting level of human chorionic gonadotropin, courses of chemotherapy required to achieve complete remission, and toxicity related to chemotherapy treatments were collected.

RESULTSThirty-seven patients with low-risk GTT totally received 137 cycles of MTX between Oct. 1999 and Sep. 2002, 34 patients (91.9%) achieved complete remission. Twenty-nine patients received multiple courses of MTX, complete remission was induced in 26 patients (89.7%). The complete response rates of I stage and III stage were 100.0% and 70.0% (P = 0.03) respectively in patients who were received multiple courses of MTX. However, eight patients received single course of chemotherapy, 7 patients achieved complete remission, and 1 achieved complete remission after another additional course of MTX was conducted. Grade III side effects (WHO criteria) only appeared in 7 courses (5.1%) during MTX treatment. Follow-up data showed that only one patient with single course of chemotherapy relapsed after 6 months.

CONCLUSIONSingle MTX chemotherapy may be effective and well tolerated for low-risk GTT.

Adolescent ; Adult ; Antimetabolites, Antineoplastic ; administration & dosage ; Choriocarcinoma ; drug therapy ; Drug Administration Schedule ; Female ; Gestational Trophoblastic Disease ; drug therapy ; Humans ; Methotrexate ; administration & dosage ; Pregnancy ; Uterine Neoplasms ; drug therapy

This study aimed to examine whether ophiopogonin D (OP-D) is capable of protecting cardiomyocytes against DOX-induced injury and the mechanisms involved. H9c2 cells were cultured. MTT assay was used to evaluate cell viability and toxicity. Mito-tracker as fluorescence probe was used to measure ROS content raised from mitochondria. The mRNA and protein expression of ATF6alpha, GRP78 and CHOP were analyzed using real-time PCR and Western blotting, respectively. The results showed that a significant endoplasmic reticulum stress (ERS) was induced upon exposure of H9c2 cells to DOX as indicated by the increase in the expression of ERS related proteins, which was paralleled with the accumulation of reactive oxygen species (ROS) and decrease in the viability of H9c2 cells. Whereas, DOX-induced ROS accumulation and up-regulation of ERS related proteins were partially abolished by pretreatment with OP-D. Consequently, a DOX-induced ERS was mitigated by application of OP-D. Similarly, DOX-induced decrease in cell viability was partially attenuated by either inhibiting CHOP or pretreatment with N-acetylcysteine (NAC), an antioxidant. Moreover, cardiac ultrastructural abnormalities seen in mouse receiving DOX injections were obviously ameliorated by pretreatment of OP-D. Taken together, the present study proved that OP-D protects cardiomyocytes against DOX-induced injury, at least in part, through reducing ROS accumulation and alleviating ERS.
Acetylcysteine ; Activating Transcription Factor 6 ; metabolism ; Animals ; Antioxidants ; Cell Line ; Cell Survival ; Doxorubicin ; adverse effects ; Endoplasmic Reticulum Stress ; drug effects ; Heat-Shock Proteins ; metabolism ; Mice ; Mitochondria ; metabolism ; Myocytes, Cardiac ; drug effects ; Rats ; Reactive Oxygen Species ; metabolism ; Saponins ; pharmacology ; Spirostans ; pharmacology ; Transcription Factor CHOP ; metabolism ; Up-Regulation

OBJECTIVESTo evaluate the relationship between Modic change and disc height together with lumbar hyperosteogeny and study the role of Modic change in lumbar degeneration.

METHODSThe imaging data of 150 elderly patients with chronic low back pain were analysed retrospectively. All patients underwent MRI and lumbar lateral X-ray examination. The lumbar disc from L1-L2 to L5-S1 were selected for this study, including 750 discs, vertebral and endplate close to disc in 150 patients. The incidence rate of lumbar endplate Modic change, disc height and the degree of vertebral bone hyperplasia were recorded. The ratio of disc height/lumbar intervertebral disc height < 50% was defined as disc collapse. The patients were divided into 4 groups in the basis of imaging changes. Group A1:disc collapse without severe lumbar hyperosteogeny; Group A2: disc collapse with severe lumbar hyperosteogeny; Group B1: Neither disc collapse nor severe lumbar hyperosteogeny; Group B2: severe lumbar hyperosteogeny without disc collapse. The incidence rates of Modic change were compared between the 4 groups by χ(2) test. Finally, the influence of disc height and vertebral bone hyperplasia on the incidence rate of Modic change was analysed.

RESULTSFour groups of patients observed a total of 750 discs. The number of intervertebral discs in the group A1 was 208, the incidence rate was 54.3%. The number of intervertebral discs in the group A2 was 135, the incidence rate of group A2 was 34.8%. The number of intervertebral discs in the B1 group was 225, the incidence rate of group B1 was 16.9%. The number of intervertebral discs in the B2 group was 182, the incidence rate of group B2 was 29.7%. There was significant difference of lumbar endplate Modic change incidence rate among the 4 groups(χ(2) = 69.565, P < 0.05). The results of post hoc test showed that the incidence rate of Modic change in group A1 was higher than group A2, B1 and B2 (χ(2) = 12.524, 66.701 and 24.102, P < 0.00714). There was significant difference of Modic change incidence rate between group A2 and B1(χ(2) = 15.032, P < 0.00714), but there was no significant difference of Modic change incidence rate between group A2 and B2 (χ(2) = 0.945, P > 0.00714) . There was significant difference of Modic change incidence rate between group B2 and group B1 (χ(2) = 9.395, P < 0.00714).

CONCLUSIONSThe incidence rate of Modic change with disc collapse but without severe lumbar hyperosteogeny is high in elderly patients with chronic low back pain. There is no significant difference of Modic change incidence between patients with both disc collapse and severe lumbar hyperosteogeny and patients with severe lumbar hyperosteogeny but without disc collapse.

Aged ; Aged, 80 and over ; Female ; Humans ; Intervertebral Disc ; pathology ; Intervertebral Disc Degeneration ; pathology ; Low Back Pain ; pathology ; Lumbar Vertebrae ; pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Retrospective Studies