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

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

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

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 clone migfilin-N terminal sequence into E.coli and obtain a fusion protein for preparing rabbit polyclonal antibody against migfilin, thereby facilitating the study of the role of migfilin in the biological behavior of colon cancer.

METHODSBased on human migfilin cDNA sequence, a pair of primers was designed to amplify migfilin-N terminal sequence by PCR. The PCR product was subcloned into the bacterial expression vector pGEX-4T-1 with EcoRI/XhoI sites, and the target recombinant plasmids were identified with enzymatic cleavage followed by DNA sequence analysis. By transforming the expression vector into component E.coli BL(21) cells, the GST-migfilin-N fusion protein was expressed with IPTG induction. Glutathione-sepharose beads were used to purify the fusion protein, and anti-migfilin polyclonal antibody was produced by immunization of rabbits with the purified GST-migfilin N-terminal fusion protein. The resultant anti-migfilin polyclonal antibody was purified by protein A beads and used for Western blotting for detecting migfilin expression in different cell lines.

RESULTS AND CONCLUSIONThe migfilin-N terminal gene fragment was cloned successfully, and purified GST-migfilin N-terminal fusion protein and anti-rabbit migfilin polyclonal antibodies were obtained. Western blot analysis demonstrates that the antibodies specifically detected migfilin expression in the cell lines, which may facilitate further investigation of the role of migfilin in the biology of colon cancer.

Animals ; Antibodies, Monoclonal ; biosynthesis ; immunology ; isolation & purification ; Base Sequence ; Blotting, Western ; Cell Adhesion Molecules ; genetics ; immunology ; Cell Line, Tumor ; Cloning, Molecular ; Colonic Neoplasms ; genetics ; metabolism ; pathology ; Cytoskeletal Proteins ; genetics ; immunology ; DNA, Complementary ; chemistry ; genetics ; Escherichia coli ; genetics ; Humans ; Molecular Sequence Data ; Rabbits ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; immunology ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA

Single-Strand Conformation Polymorphism(SSCP) is an effect method for investigating environment microbial genetic polymorphism, with its characterization of rapidness, simplicity, and sensitivity. However, many factors can influence the results of SSCP in the analysis of complex environment samples, and its optimization is highly needed. In this paper, optimal PCR-SSCP conditions were discussed based on PAGE concentration, formamide deionized in denaturing loading buffer, electrophoresis time and temperature. The resluts showed that the optimal conditions were as follows: 16S rDNA V1~V3 was selected as the targeted gene, the ratio of acrylamide to N, N-dimethylacrylamide in 12% polyacrylamide gel electrophoresis(PAGE)gel was 49:1, the ratio of formamide deionized in denaturing loading buffer was 1:3, running the SSCP gel at 300 V for 18 h (under 4 ℃). Aside from this, the validations using samples from a simultaneous desulfurification and denitrification bioreactor were conducted under this optimal conditions.

BACKGROUNDSerum tumor markers have always been of clinical importance in the diagnosis, monitoring disease progression and therapy efficacy for patients with malignant diseases. However, elevated serum tumor markers are found in some benign conditions, especially in chronic kidney disease (CKD). The elevation of them in CKD might cause confusion and misuse of these tumor markers. We conducted this retrospective study to investigate which of the five widely used tumor markers including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), cytokeratin 19 fragment antigen 21-1 (Cyfra21-1), squamous cell carcinoma antigen (SCC) and neuron specific enolase (NSE) are affected markedly by CKD, in order to use them more effectively.

METHODSSerum tumor marker concentrations, biochemical, hematological parameters, and urinalysis were measured in CKD patients and healthy controls. The positive rate and median tumor markers' level in CKD patients and controls, and those in CKD patients stratified by CKD grade were compared using nonparametric rank tests. Correlation analysis of serum tumor markers and other parameters in CKD patients were performed using the Spearman correlation coefficient. Multivariate Logistic regression analysis was used to estimate the important variables that caused elevated serum concentrations of these markers in CKD patients.

RESULTSThe overall positive rates and serum concentrations of Cyfra21-1, SCC, CEA in CKD group were significantly higher than those in control group. Positive rate and serum concentrations of those tumor markers increased as kidney function decreased. Both univariate analysis and multivariate regression analysis showed that the elevations of those tumor markers were not only associated with kidney function, but also with nutritional status.

CONCLUSIONSSerum concentrations of Cyfra21-1, SCC, CEA are significantly influenced by kidney function, as well as nutritional status. Therefore, in clinical work, the indices of kidney function and nutritional status could be simultaneously measured to improve interpretation of the results of those tumor marker concentrations.

Adult ; Aged ; Antigens, Neoplasm ; blood ; Biomarkers, Tumor ; blood ; Carcinoembryonic Antigen ; blood ; Female ; Glomerular Filtration Rate ; Humans ; Keratin-19 ; blood ; Logistic Models ; Male ; Middle Aged ; Nutritional Status ; Renal Insufficiency, Chronic ; blood ; Retrospective Studies ; Serpins ; blood ; alpha-Fetoproteins ; analysis