OBJECTIVE:To develop an HPLC method for the determination of 5-ISMNconcerntrations in human plasma and study the pharmacokinetics of 5-ISMN orally disintegrating tablets and the reference tablets.METHODS:A single oral dose test capsule(orally disintegrating tablets)or reference capsule of 5-ISMN(60 mg)were administered by randomized crossover way in 20 healthy male volunteers with plasma 5-ISMN concentrations determined by HPLC.The pharmacokinetic parameters were calculated with 3p87 pharmacokinetic program and the bioavailability of the two preparations was evaluated.RESULTS:The main pharmacokinetic parameters of the test preparation vs.the reference preparation were as follows:Cmax:(613.42?73.83)vs.(368.64?38.66)?g?mL-1;tmax:(26.52?2.00)vs.(95.73?4.16)min;AUC0～∞:(73 872.24?543.89)vs.(77 978.47?646.37)ng?min?mL-1,respectively.CONCLUSION:The assay was proved to be sensitive,accurate and suitable for pharmacokinetic study of 5-ISMN.The results of pharmacokinetic study after oral administration of test and reference preparations of 5-ISMN showed that the two preparations were bioequivalent while the test preparation had a higher peak concentration and could reach peak level in less time,and the test preparation showed a rapid drug releasing behavior.

Flavonoids are natural products that are ubiquitous in the natural world, with wide physiological activities and low toxic and side effects. In recent years, their anti-tumor effect has caused widespread concern and studies. According to the findings, flavonoids have prominent effects in preventing and treating lung cancer, breast cancer, colon cancer, prostate cancer, liver cancer, leukemia, ovarian cancer, gastric cancer and so on. Their anti-tumor mechanisms mainly include anti-oxidation, anti-free radical, induction of apoptosis of cancer cells, impact on cell cycle, immune regulation, inhibition of tumor angiogenesis, inhibition of COX-2, inhibition of telomerase activity and so on. This article focuses on the advance in domestic and foreign studies on anti-cancer activity and mechanism of flavonoids, in order to provide theoretical basis and research ideas for the further development and clinical application of flavonoids.
Animals ; Antineoplastic Agents ; pharmacology ; Antioxidants ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Flavonoids ; pharmacology ; Humans

Clove oil and turmeric oil were absorbed by mesoporous carbon. The absorption ratio of mesoporous carbon to volatile oil was optimized with the eugenol yield and curcumol yield as criteria Curing powder was characterized by scanning electron microscopy (SEM) and differential scanning calorietry (DSC). The effects of mesoporous carbon on dissolution in vitro and thermal stability of active components were studied. They reached high adsorption rate when the absorption ratio of mesoporous carbon to volatile oil was 1:1. When volatile oil was absorbed, dissolution rate of active components had a little improvement and their thermal stability improved after volatile oil was absorbed by the loss rate decreasing more than 50%. Absorbing herbal volatile oil with mesoporous carbon deserves further studying.
Adsorption ; Carbon ; chemistry ; Drug Stability ; Microscopy, Electron, Scanning ; methods ; Oils, Volatile ; chemistry ; Sesquiterpenes ; chemistry

To investigate the effect of flavonoids from Sophora flavescens in aging mice induced by D-galactose and its mechanism. Totally 60 mice were randomly divided into six groups: the control group, the model group, the piracetam group (positive control group) and flavonoids from S. flavescens low, medium and high doses groups. Except for the control group, all of the rest groups were subcutaneously injected with D-galactose (160 mg x kg(-1)) for successively 30 days to establish the sub-acute senescent model. Meanwhile, flavonoids from S. flavescens low, medium and high doses groups were respectively administered with 150, 300 and 600 mg xkg-('1)of flavonoids from S. flavescens for 30 days. The learning and memory abilities of mice were determined by avoiding darkness ex-eriment and jumping stair experiment. The contents of malondialdehyde (MDA) tumor necrosis factor-aα NF-aα the activities of superoxide dismutase (SOD) monoamine oxidase-B (MAO-B) Na'(+)K'(+)-ATPase and Ca2(+ )-ATPase in the brain of mice were deter-ined respectively after the behavioral experiments. The activity of lactic dehydrogenase ( DH) in blood serum was also determined and analyzed by microscope after HE staining to observe the changes in hippocampal organizational structure. Compared with the model group, flavonoids from S. favescens medium and high doses groups showed significantly increases in the latency of avoiding darkness and jumping stair experiments; flavonoids from S. fllvescens low, medium and high doses groups and the piracetam group showed de-reases in the numbers of errors in avoiding darkness experiment; the flavonoids from S. flavescens high dose group and the piracetam group showed reduction- n the number of errors in jumping stair experiment (P <0 . 5 or P <0 . 1). Flavonoids from S. flavescens me-ium and high doses groups and the piracetam group showed improvements in the activities of SOD, Na'(+)K'(+)ATPase in the brain of mice and declines in the contents of MDA and TNF-aα the activity of MAO-B in the brain of mice, the activity of LDH in blood serum (P <0 . 5 or P <0 . 1). Flavonoids from S. flavescens low, medium and high doses groups and the piracetam group also showed im-rovement in the activity of Ca2(+ )ATPase, with statistical difference from the model group (P <0 . 5 or P <0 . 1). The pathological result showed decreases in the number of cells of hippocampal dentate gyrus area, sparse cell arrangement, incomplete cellular mor-hology, scarce cytoplasm, blurred boundary between nucleus and cytoplasm, nuclei anachromasis, irregular pyknosis and unconspicu-us nucleoli in the model group. Compared with the model group, flavonoids from S. flavescens low, medium and high doses groups and the piracetam group showed improvements in hippocampal organization tissues. Flavonoids from S. favescens can improve the learning and memory ability of senescent mice induced by D-galactose. Its mechanism may be correlated with the enhancement of anti-oxidative actions by lowering TNF-aαcontent, which results in the stability of cell membrane and the reduction in MAO-B activity.
Aging ; drug effects ; metabolism ; psychology ; Animals ; Brain ; drug effects ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Flavonoids ; administration & dosage ; Galactose ; adverse effects ; Hippocampus ; drug effects ; metabolism ; Humans ; Learning ; drug effects ; Male ; Malondialdehyde ; metabolism ; Mice ; Sophora ; chemistry ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

BACKGROUNDIntravoxel incoherent motion (IVIM) has the potential to provide both diffusion and perfusion information without an exogenous contrast agent, its application for the brain is promising, however, feasibility studies on this are relatively scarce. The aim of this study is to assess the feasibility of IVIM perfusion in patients with acute ischemic stroke (AIS).

METHODSPatients with suspected AIS were examined by magnetic resonance imaging within 24 h of symptom onset. Fifteen patients (mean age was 68.7 ± 8.0 years) who underwent arterial spin labeling (ASL) and diffusion-weighted imaging (DWI) were identified as having AIS with ischemic penumbra were enrolled, where ischemic penumbra referred to the mismatch areas of ASL and DWI. Eleven different b-values were applied in the biexponential model. Regions of interest were selected in ischemic penumbras and contralateral normal brain regions. Fast apparent diffusion coefficients (ADCs) and ASL cerebral blood flow (CBF) were measured. The paired t- test was applied to compare ASL CBF, fast ADC, and slow ADC measurements between ischemic penumbras and contralateral normal brain regions. Linear regression and Pearson's correlation were used to evaluate the correlations among quantitative results.

RESULTSThe fast ADCs and ASL CBFs of ischemic penumbras were significantly lower than those of the contralateral normal brain regions (1.93 ± 0.78 αμm2/ms vs. 3.97 ± 2.49 αμm2/ms, P = 0.007; 13.5 ± 4.5 ml·100 g-1·min-1 vs. 29.1 ± 12.7 ml·100 g-1·min-1, P < 0.001, respectively). No significant difference was observed in slow ADCs between ischemic penumbras and contralateral normal brain regions (0.203 ± 0.090 αμm2/ms vs. 0.198 ± 0.100 αμm2/ms, P = 0.451). Compared with contralateral normal brain regions, both CBFs and fast ADCs decreased in ischemic penumbras while slow ADCs remained the same. A significant correlation was detected between fast ADCs and ASL CBFs (r = 0.416, P < 0.05). No statistically significant correlation was observed between ASL CBFs and slow ADCs, or between fast ADCs and slow ADCs (r = 0.111, P = 0.558; r = 0.200, P = 0.289, respectively).

CONCLUSIONSThe decrease in cerebral blood perfusion primarily results in the decrease in fast ADC in ischemic penumbras; therefore, fast ADC can reflect the perfusion situation in cerebral tissues.

Aged ; Brain Ischemia ; pathology ; physiopathology ; Cerebrovascular Circulation ; physiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Prospective Studies ; Stroke ; pathology ; physiopathology

BACKGROUNDMonilethrix is an autosomal dominant hair disorder characterized clinically by alopecia and follicular papules. In this study, we collected a Han monilethrix family to detect the mutations in patients and investigated the correlation between the genotype and phenotype of monilethrix.

METHODSIn this study, we identified a Chinese family with monilethrix through light microscopic and scanning electron microscopic (SEM) examination. Genomic DNA from peripheral blood samples was prepared. DNA samples from controls and monilethrix patients were subject to polymerase chain reaction (PCR) amplification. Two pairs of primers were used to amplify the seventh exon of KRT86. Mutation screening of the PCR products was detected using direct sequencing.

RESULTSLight microscopic examination showed a regular alternate enlargement and narrow area. SEM examination showed that part of the cuticle of the nodules shed and disappeared gradually in the narrow area with granular protrusions on the surface similar to the erosion-like structure. Parallel longitudinal ridge and groovepattern appeared, and the ridges varied in width, like dead wood. A heterozygous transversion mutation c.1204G > A (p.E402K) in the seventh exon of KRT86 was identified in both patients.

CONCLUSIONSThe mutation of extron 7 of KRT86 identified plays a major role in the pathogenesis of this pedigree with monilethrix, and is a mutation hot spot of KRT86. Further research is needed to explore the relationship between the phenotype and the mutation of the type II hair keratin gene KRT86 of monilethrix.

Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Humans ; Keratins, Hair-Specific ; genetics ; Keratins, Type II ; genetics ; Microscopy, Electrochemical, Scanning ; Monilethrix ; etiology ; genetics ; pathology ; Mutation

OBJECTIVETo study the metabolic difference of body influenced by active stress and passive stress under special events.

METHODSTo detect serum multiple biochemistry index of 57 earthquake rescue medical team and 13 victims of a natural calamity in Wenchuan earthquake by using Hitachi 7600 automatic analyzer.

RESULTSStress affected biochemistry index deeply. To compared with rescue medical team, the serum ADA, ALP and TG of victims increased obviously and TP, ALB, MAO, Cr, UA, K, Na, Cl, Ca, ApoA1 and HDL decreased obviously.

CONCLUSIONMany biochemistry index have been changed under stress and it relate with stress extent. The human body function status was better in active stress than in passive stress.

Blood Chemical Analysis ; China ; Disasters ; Earthquakes ; Humans ; Metabolism ; physiology ; Rescue Work ; Stress, Physiological ; physiology

OBJECTIVETo investigate the feasibility of peptide mass fingerprinting for non-invasive differential diagnosis of IgA nephropathy (IgAN) from the non-IgA nephropathy (IgAN).?

METHODSAccording to the results of renal biopsy, 56 patients were divided into IgAN group (n=28) and non-IgAN group (n=28), and peptide mass fingerprints were acquired from these patients using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

RESULTSNine different peptides were identified between IgAN and non-IgAN. The two most distinctive differentially expressed peptides, with peptide peak values of 4476.46 and 1968.10, showed area under curve values of 86.18% and 79.77%. Principal component analysis demonstrated that the accumulated explained variance of the first 8 differential peptides reached 95%, suggesting the feasibility of differential diagnosis of IgAN from non-IgAN. Comparison with the Matrix protein database identified the peptide with a relative molecular mass of 5338.08 as a fragment of mucin 4 inform and the 2082.77 peptide as fragment of α1-II type collagen inform.

CONCLUSIONMALDI-TOF MS is feasible for differential diagnosis of IgAN and non-IgAN and also has great potentials in the classification of the subtypes of other systemic diseases.

Adult ; Diagnosis, Differential ; Feasibility Studies ; Female ; Glomerulonephritis, IGA ; diagnosis ; Humans ; Kidney Diseases ; diagnosis ; Male ; Middle Aged ; Peptide Mapping ; methods ; Peptides ; chemistry ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods ; Young Adult

OBJECTIVETo investigate composition principle of Yinqiao-decoction through experiment of anti-influenza.

METHODSThe effects of different compositions of Yinqiao-decoction on the index of hemagglutinin titre of virus in the lung tissue of mice infected with virus from nose were investigated by orthogonal design.

RESULTSAccording to the hemagglutinin titre of virus in the lung tissue of mice, the necessary effective drugs of Yinqiao-decoction are forsythia suspense, flos lonicerae, fructus arctii, schizonepeta tenuifolia, folium phyllostach lophatheri, glycyrrhiza uralensis, platycodon grandiflorum and mentha haplocalyx, and semen sojae preparatum isn't necessary. There is interaction between forsythia suspense and flos lonicerae, forsythia suspense and fructus arctii, forsythia suspense and schizonepeta tenuifolia, fructus arctii and mentha haplocalyx, schizonepeta tenuifolia and platycodon grandiflorum.

CONCLUSIONThe optimal combination of Yinqiao-decoction is flos lonicerae, forsythia suspense, fructus arctii, folium phyllostach lophatheri, glycyrrhiza uralensis, mentha haplocalyx of the second level and schizonepeta tenuifolia, platycodon grandiflorum, semen sojae preparatum of the first level.

Animals ; Anti-Infective Agents ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Lung ; virology ; Male ; Mice ; Orthomyxoviridae ; metabolism ; Orthomyxoviridae Infections ; drug therapy ; virology

OBJECTIVETo observe the effect of human cytomegalovirus infection on the host cellular DNA synthesis and expression of cyclones.

METHODSHCMV infected cell was established in vitro by incubating passage cultured HEL and HCMV AD169 strain with different titres. The cells were synchronized in the G0/G1 stage by contact inhibition and infected with strain AD169 of HCMV at an MOI of 5 PFU per cell. We harvested infected cell at different time 0 h, 3 h, 6 h, 24 h, 72 h and 96 h post infection. Then the cell cycle progress was measured. Meanwhile, the DNA content and expression of proteins of cycline E, cycline A and cycline D1 were determined with FCM and Western Blot respectively.

RESULTSWe found that the amount of S stage cell infected by HCMV had increased dramatically, and that of G2/M stage cell reduced during 24 h-96 h PI, and no G2/M stage cell was detected within 96 h PI. The content of 2N DNA maintained unchangeable for 24 h after infection and the content of total DNA in infected cells began to increase within 48 h PI, and the substantial cell with 2N DNA were observed 72 h after infection. However, DNA content was not altered in control group of normal HEL and HCMV PAA group. CyclinE protein was induced 12 h PI and peak induction occurred 24 h PI in contact-inhibited cells. CyclinA protein expression was not induced in HCMV infected density-arrested cells. The abundance of cyclinD1 decreased 24 h PI.

CONCLUSIONThe expression of cyclinE and activity of cyclinE/Cdk2 kinase are increased obviously in G0/G1 stage cells infected with HCMV, which may induce the cell cycle to overpass G1/S restriction point and make the cell cycle arrested in later G1 stage. HCMV can not activate cellular DNA synthesis, and increase of total DNA content in infected cells result from the viral DNA replication.

Cell Cycle ; Cells, Cultured ; Cyclins ; genetics ; metabolism ; Cytomegalovirus ; physiology ; Cytomegalovirus Infections ; genetics ; metabolism ; Gene Expression ; Humans