Rutaecarpine (Rut) is a type of indole quinazoline alkaloid exracted from Ruticarpum. Studies showed that Rut has a wide range of pharmacological effects, such as anti-hypertension, anticancer, anti-inflammation, anti-thrombus formation. Currently, many scholars are committed to developing it into a new antihypertensive and anti-inflammatory drug with all new mechanisms. But studies found that Rut is a highly fat-soluble drug with low water and oil solubility. Its high insolubility is the main obstacle in its oral absorption and application, which greatly reduced its bioavailability. Therefore, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was used as the inclusion material to prepare Rut-HP-beta-CD inclusion complex in this experiment, in order to increase its water solubility and bioavailability. In this experiment, the inclusion complex was prepared by the stirring-freeze-dry method. The preparation process was optimized by the orthogonal test, with the inclusion rate as the index, and molar ratio between host and guest molecules, inclusion temperature, time and stirring speed as the impacting factors. Moreover, the inclusion complex was verified by detecting the apparent solubility, thin layer chromatography, microscopic identification, melting point detection and dissolution study. The results showed that under the conditions of the molar ratio between Rut and HP-beta-CD of 1: 1, temperature at 60 degrees C, inclusion time of 4h and stirring speed at 600 r x min(-1), the inclusion rate of Rut-HP-beta-CD reached 91.04%. Therefore, the preparation process of Rut-HP-beta-CD inclusion under the optimum conditions is simple and feasible, with a highest inclusion rate and reproducibility, and could significantly improve Rut's solubility and bioavailability, and provide a reliable experimental basis for its clinical application.
2-Hydroxypropyl-beta-cyclodextrin ; Alkaloids ; chemistry ; Chemistry, Pharmaceutical ; methods ; Drug Carriers ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Rutaceae ; chemistry ; Solubility ; beta-Cyclodextrins ; chemistry

Objective To analyze the epidemiological characteristics of Mycobacterium tuberculosis by enterbaeterial repetitive intergenic consensus-polymerase chain reaction(ERIC-PCR)DNA fingerprint. Methods Mycobacterium tuberculosis positive sputum samples between September 2003 to May 2006 were collected and cultured.Chromosomal DNA were extracted and ERIC-PCR DNA fingerprinting was analyzed by software,such as RAPD PHYLIP and Treeview.Results A total of 42 different fingerprints were detected.Phylogenetic analysis showed that they could be classified into three clusters,the clustering rate was 72.6%.The characteristics of ERIC-PCR fingerprint patterns were related to age,drug resistance,and type of resistance.Conclusions ERIC-PCR DNA fingerprinting technique used in this study is good for epidemiological studies with its strong discrimination,simplicity and rapidness.A high level of recent transmission is found in our city.

Objective To evaluate the value of ultrasound biomicroscopy (UBM) in assessment of atherosclerosis in apolipoprotein E (ApoE) knockout mice feeding with western diet.Methods Sixteen ApoE knockout mice in 8 weeks age were selected,then divided into two groups.One group was fed with west diet as high-fat group,and another group was fed with normal diet as control group.Intima-media thickness (IMT) and plaque area in the aortic root were assessed by UBM in two groups after 8 weeks and 16 weeks.And the measurements of UBM were compared with results of histopathology and blood-fat.ResultsThicken wall and plaque could be find in aortic root in control group and high-fat diet group byUBM.IMT and plaque area in high-fat diet group was significantly higher than those of control group ( P ＜ 0.05).The IMT and plaque area in UBM were good correlation with histopathology ( rwas 0.81 and 0.70 respectively).The triglyceride(TC) and total cholesterol in high-fat diet group was significantly higher than those of control group ( P ＜0.05),and IMT in UBM were increased with the elevated level of TC,there was a positive correlation between IMT and TC( r =0.528).ConclusionsWestern diet can accelerate the process in formation of atherosclerotic plaque in ApoE knockout mice.UBM can be used to observe this prograss noninvasively in vivo mice.

Objecfive To study the effect of Danhong injection(DI)on intimal hyperplasia and expressions of basic fibroblast growth factor(bFGF)and tissue factor(TF)in carotid arteries of rabbits after percutaneous transluminal angioplasty(PTA). Methods Fifty New Zealand White rabbits were randomly divided into 5 groups (n=10),namely sham-operated group,model group,and DI treatment groups(low-,medium-and high-dose DI treatment groups).The animals in the sham-operated group were only given external carotid artery ligation.The rabbit models of carotid stenosis in the later 4 groups were established by ballon-injury.Before the carotid balloon injury,the animals in the DI treatment groups were given DI at doses of 1 mL/kg·d-1,2mL/kg·d-1 and 4 mL/kg·d-1,respectively,for 7 or 14 d via intravenous injection;the animals in the sham-operated and model groups were given saline solution(2mL/kg·d-1)instead.The animals were sacrificed and their common carotid arteries were removed on the 7th and 28th d of surgery;morphology changes of the arterial wall with hematoxylin eosin staining were observed by optical microscope,and the expressions ofbFGF and TF of the vascular wall were detected through immunohistochemical techniques;with the help of an image analysis system,semiquantitative analysis was performed.Results On the 7th d of surgery,the intimal area and intima area/media area (I/M)ratio in the model group showed no significant differences as compared with those in the other 4groups(P>0.05).On the 28th d of surgery,the intimai area and I/M ratio in the model group were increased markedly as compared with those in the sham-operated group (P<0.05), and the intimal area and I/M ratio in the medium and high dose DI treatment groups were significantly reduced as compared with those in the in the model group (P<0.05). The expressions of TF and bFGF in the neointima of carotid arteries of rabbits treated with medium and high dose of DI were significantly weaker than those of the model group (P<0.05), and those of rabbits treated with low dose of DI had no obvious differences as compared with those of the model group (P>0.05). Conclusion Medium and high dose of DI can inhibit the intimal hyperplasia resulting from percutaneous transluminal angioplasty, might through the inhibition of expressions of bFGF and TF in the neointima of the arterial wall.

OBJECTIVETo study the effects of intestinal microflora alteration on specific and nonspecific immune function and hematopoietic function of mice.

METHODSSixty BALB/C mice were divided at random into two groups, experimental group and control group, with 30 mice in each. The mice in the experimental group were given kanamycin 50 mg while those in the control group were given distilled water intragastrically everyday for consecutive 10 days. After the 10 day treatment all the mice were sacrificed, and the cecal contents were collected for quantitative analysis of the intestinal bacterial flora. Certain indexes of immune function, including phagocytosis rate of macrophages, number of T lymphocytes positively stained by esterase and serum interleukin 2 (IL-2) content, and the weight of the spleen, granulocyte-macrophage colony stimulating factor etc. as indexes of hematopoietic function were determined.

RESULTSIn the group, the quantity of Enterobacteriaceae, Enterococcus, Bifidobacterium and Lactobacillus were significantly lower than that in the control group (P < 0.01). The number of PFC (plaque forming cells), the phagocytosis rate of macrophage, the number of T lymphocytes with positive NANE staining, the level of IL-2 significantly decreased when compared with that in the control group (P < 0.01). The weight of the spleen in the experimental group decreased when compared with that in the control group (P < 0.01). Levels of IL-3, GM-CSF, the total number of WBC and the proportion of neutrophil remarkably decreased as compared to that in the control group (P < 0.01). Analysis of the correlations between normal microflora, immunologic and hematopoietic indexes showed that marked positive correlations between the quantity of Bifidobacteria and each immune index including the levels of IL-3 and GM-CSF. There was a positive correlation between IL-2 and IL-3, IL-2 and GM-CSF as well.

CONCLUSIONThe application of antibiotics may cause changes in the structure and quantity of intestinal microflora. The dysbacteriosis may decrease the immune function of organism. The dysbacteriosis may decrease the hemopoietic function. The dysbacteriosis, the decrease in immune and hematopoietic function may affect one another. The balance in microecosystem should be emphasized and antibiotics should be applied rationally to reduce the side effects such as dysbacteriosis.

Animals ; Anti-Bacterial Agents ; pharmacology ; Esterases ; biosynthesis ; Feces ; microbiology ; Granulocyte-Macrophage Colony-Stimulating Factor ; analysis ; Interleukin-2 ; blood ; Intestines ; drug effects ; microbiology ; Kanamycin ; pharmacology ; Macrophages ; drug effects ; physiology ; Mice ; Mice, Inbred BALB C ; Models, Animal ; Organ Size ; Phagocytosis ; drug effects ; Spleen ; drug effects ; pathology ; T-Lymphocytes ; drug effects ; metabolism

OBJECTIVETo investigate the anti-mutagenic action of the total flavonoids of Astragalus (TFA).

METHODThree groups of concentrations of TFA and one inducer group were used. The anti-mutagenic action of TFA was studied by experiments in vitro and in vivo including miconucleolus assay, semen teraogenesis test and gene mutagenesis of V79/HGPRT.

RESULTTFA did not affect the weight of the mice during the experiment period. The high concentration of TFA could significantly reduce cyclohophamide-induced miconucleolus number and gene mutagenesis of V79/HGPRT compared with inducer group. However, TFA did not make statistic change in the semen teraogenesis induced by mitomycin C.

CONCLUSIONTFA has antimutagenesis effect.

Animals ; Antimutagenic Agents ; isolation & purification ; pharmacology ; Astragalus membranaceus ; chemistry ; Cells, Cultured ; Chromosome Aberrations ; drug effects ; Cricetinae ; Cricetulus ; Flavonoids ; isolation & purification ; pharmacology ; Male ; Mice ; Micronucleus Tests ; Mutagenesis ; drug effects ; Plants, Medicinal ; chemistry ; Testis ; cytology ; drug effects

OBJECTIVETo study the stereoselective glucuronidation of carvedilol (CARV) by three Chinese liver microsomes.

METHODSThe metabolites of CARV were identified by a hydrolysis reaction with beta-glucuronidase and HPLC-MS/MS. The enzyme kinetics for CARV enantiomers glucuronidation was determined by a reversed phase-high pressure liquid chromatography (RP-HPLC) assay using (S)-propafenone as internal standard after precolumn derivatization with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylisothiocyanate.

RESULTSTwo CARV glucuronides were found in three Chinese liver microsomes incubated with CARV. The non-linear regression analysis showed that the values of K(m) and V(max) for (S)-CARV and (R)-CARV enantiomers were (118+/-44) micromol/L, (2 500+/-833) pmol/(min.mg protein) and (24+/-7) micromol/L, (953+/-399) pmol/(min.mg protein), respectively.

CONCLUSIONThese results suggested that there was a significant (P<0.05) stereoselective glucuronidation of CARV enantiomers in three Chinese liver microsomes, which might partly explain the enantioselective pharmacokinetics of CARV.

Carbazoles ; metabolism ; China ; Glucuronic Acid ; metabolism ; Glucuronides ; metabolism ; Microsomes, Liver ; metabolism ; Propanolamines ; metabolism ; Stereoisomerism

BACKGROUNDPulmonary embolism (PE) is rare and seldom considered in adolescent patients; however it occurs with a greater frequency than is generally recognized, and it is a potentially fatal condition. The aim of the current study was to understand its epidemiology, clinical features and the cause of delay of its diagnosis in adolescents.

METHODSA retrospective analysis of nine adolescents with acute PE admitted to the Peking University Third Hospital over the past 16-year period was performed. The epidemiology, clinical features and risk factors of the adolescents were described and compared with those of adults and elderly patients. The time to diagnosis and misdiagnosed diseases were analyzed. Pretest probability of PE was assessed retrospectively by the Wells score and revised Geneva score.

RESULTSThe incidence of PE was 43.6 per 100 000 hospitalized adolescents in our hospital. The incidence of PE in adolescents was much lower than that in adults and PE is diagnosed in about 1/50 of elderly people. The clinical features in adolescents were similar to those in adults. But fever and chest pain were more common in adolescents (P < 0.05). The major risk factors included surgery, systemic lupus erythematosus (SLE), thrombocytopenia, long-term oral glucocorticoids and trauma. The mean diagnostic time was (7.8 ± 8.4) days. Six cases had a delayed diagnosis. The mean delay time from symptom onset to diagnosis was (11.0 ± 8.8) days. The time of presentation to diagnosis in patients initially admitted to the emergency department was less than one day, and was much shorter than the time in outpatients, (9.4 ± 7.5) days. Most of the patients were initially misdiagnosed with a respiratory tract infection. Most patients' values of Wells score or revised Geneva score were in the moderate or high clinical probability categories; 88% by Well score vs. 100% by revised Geneva score.

CONCLUSIONSPE was seldom considered in the adolescent patients by physicians, especially outpatient physicians, so the diagnosis was often delayed. If adolescent patients complain of dyspnea or chest pain or syncope with/without fever, and they had risk factors such as surgery, thrombocytopenia and trauma, PE should be considered and included in the differential diagnosis.

Adolescent ; Adult ; Diagnosis, Differential ; Diagnostic Errors ; Humans ; Male ; Probability ; Pulmonary Embolism ; diagnosis ; epidemiology ; etiology ; Retrospective Studies ; Risk Factors

OBJECTIVETo investigate the inhibitory effect of lactic acid on semen-derived amyloid (SEVI) fibril formation.

METHODSPAP248-286 (2 mg/mL) was incubated with 4.0, 2.0, 1.0, 0.5, 0.25, and 0.125 mg/mL of lactic acid. After incubation for different times, aliquots were drawn from each sample for Thioflavin T (ThT) and Congo red staining to monitor semen-derived amyloid fibril formation. The β sheet structure formation of PAP248-286 was measured by circular dichroism spectrum, and the morphology of amyloid fibrils incubated with or without lactic acid was observed with transmission electron microscopy (TEM). The enhancing effect of amyloid fibril incubated with lactic acid at different time points was determined using virus infection assay. PAP248-286 (2 mg/mL) was incubated with dilutions of vaginal secretion from healthy women, and amyloid fibril formation was detected with ThT and Congo red staining.

RESULTSLactic acid inhibited SEVI fibril formation in a dose-dependent manner in vitro. Lactic acid at 0.5 mg/mL completely inhibited 2 mg/mL SEVI fibril formation within 48 h. After incubation for 48 h, lactic acid at 1 mg/mL inhibited the formation of β-sheet structure of SEVI (2 mg/mL) and completely inhibited 2 mg/mL PAP248-286 aggregation as observed with TEM. In the presence of lactic acid, PAP248-286 lost the ability to enhance virus infection. Vaginal secretion inhibited SEVI fibril formation in a dose-dependent manner, and virtually no SEVI fibril occurred after incubation of 2 mg/mL PAP248-286 with 67% vaginal secretion.

CONCLUSIONLactic acid inhibits SEVI fibril formation in vitro.

OBJECTIVETo separate and identify the chemical constituents of Blumea riparia.

METHODThe compounds were separated and purified by repeated silica gel, Sephadex LH -20 column chromatographiy. The structures of these compounds isolated were identified by analysis of their spectral data, physical and chemical properties.

RESULTSix flavonoids were isolated from B. riparia. and their structures were identified as eriodictyol-7, 4'-dimethyl ether (1), eriodictyol-7, 3'-dimethyl ether (2), eriodictyol-7-methyl ether (3), quercetin-7, 3', 4'-trimethyl ether (4), tamarixetin (5), rhamnocitrin (6).

CONCLUSIONCompound 1-6 were obtained from B. riparia for the first time.

Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Flavonoids ; analysis ; isolation & purification ; Magnetic Resonance Spectroscopy