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Biomedical subjects

Qiang Zhang

Publications and source records attributed to Qiang Zhang.

At least 163 records · Page 9Linked to original sources
PubMed2004

[Absorption of recombinant hirudin in rats GI tract].

AIM: To investigate the absorption and distribution of recombinant hirudin-2 (rHV2) in the GI tract in rats after oral administration. METHODS: Using HPLC, fluorescence spectrophotometry and confocal laser scanning microscopy to measure the amount of intact rHV2 absorbed into gastrointestinal mucosa and blood. RESULTS: HPLC spectrum showed that there were intact rHV2 molecules in plasma after 1 h of oral administration. After oral administration for 3 h, 1.2%-26.8% of fluorescence was found in the GI tract in rats. Chromatographic analysis showed that 2.27%-38.75% of fluorescence recovered from the GI tract luminal contents and mucosa was eluted at the void volume of a Sephadex G-25 column. Microscopic examination showed that FITC-rHV2 was taken up throughout the whole small intestine but the ileum appeared to be a preferred site for FITC-rHV2 transport in rats. CONCLUSION: rHV2 may partially survive in the GI lumen and subsequently absorbed in active form by gastrointestinal tract.

Administration, Oral↗
PubMed2004

[Forest health ecological risk assessment in China].

Forest health ecological risk assessment is an important factor in forest resources management. In this paper, we selected forest fire, forest disease-pest disasters and acid rain as main risk sources, described the risk resources by probability, intensity and distributing, and mapped each risk source. The endpoints were the damages that the risk acceptor might and these damages might cause ecosystems' organization and function changing under the uncertainty risk sources. Endpoints of forest might compose of productivity descent, reducing biodiversity, forest degrading, forest ecological function declining, furthermore, forest disappearing. We described exposure in terms of intensity, space, and time. In the exposure and hazard analysis, we used fragile index to show frangibility or resistibility (resistibility is reverse to frangibility), and analyzed the damages by different risk sources. Risk assessment and management was the integrated phase of the research. Because of the spatial heterogeneity of risk sources, all risk index were overlaid in the China map by GIS, which divided the region into 30 ecological risk sub-zones (provinces), according to risk index of each risk sub-zone, and the forest in China was divided into six levels of risk zones. In every level of risk zones, we also put forward the countermeasures for forest health ecological risk management. The result of assessment could provide scientific basis for forest management.

Animals↗
PubMed2004

[Preparation of magnetoliposomes and its in vivo behavior on ICR mice].

AIM: To prepare magnetoliposome (MLP) containing dextran-encapsulated magnetite (Fe3O4), and to examine its physicochemical properties and its in vivo behavior on ICR mice. METHODS: Reverse phase evaporation method was used to formulate MLP and the Fe2+ concentration was measured by o-phenanthroline method. Then the basic properties of MLP and in vivo distribution were studied with the aid of 3H isotope as biomarker. RESULTS: The mean diameter of MLP was 602.5 nm and the final concentration of encapsulated Fe3O4 was 88.1 mg x L(-1). Under natural conditions most of the MLP was taken up by spleen after the administration via tail vain, but its uptake was reduced under the magnetic field. There was a great difference in vivo distribution between the left and right lobes of the liver and the left and right kidneys in magnetic fields. CONCLUSION: Reverse phase evaporation method was utilized to prepare magnetoliposomes. The formulation was stable and encapsulated high amount of magnetite. The delivery system could be oriented to certain tissues under magnetic field and satisfying magnetic responsiveness was observed.

Animals↗
PubMed2004

[Determination of clonidine in rabbit plasma by HPLC-MS].

AIM: To determine clonidine in rabbit plasma by LC-MS. METHODS: The LC-MS system consisted of Waters Alliance 2790 HPLC and Micromass ZQ-4000 MS. The HPLC was performed by using XTerra C18 (150 mm x 2.1 mm ID, 5 microm). The mobile phase, consisting of acetonitrile/ammonium hydrogen carbonate solution, was maintained to a flow-rate of 0.2 mL x min(-1) and the linear gradient elution was adopted. Mass spectrum was obtained by using electrospray ionization interface and the m/z of SIM was 230. RESULTS: The average recovery was high and the method was reproducible. The calibration curve showed good linearity in the range of 1 - 80 microg x L(-1), the lowest limit of detection was 0.05 microg x L(-1). The Cmax, AUC0-t, and Tmax value of the pharmacokinetics parameter were (27 +/- 9) microg x L(-1), (5,352 +/- 1,121) microg x L(-1), (79 +/- 17) h. CONCLUSION: The results demonstrated that the method had high sensitivity, good selectivity, accuracy and precision. It is used to determine the clonidine concentration in plasma. The transdermal patch can deliver clonidine to the surface of rabbit skin stably for periods of up to 1 week after a single application.

Administration, Cutaneous↗
PubMed2004

[Transport of proteins and peptides across human cultured alveolar A549 cell monolayers].

AIM: An in vitro cultured monolayer system of alveolar epithelial cells was used as a model to investigate the transport pathway peptides or proteins, salmon calcitonin (sCT), insulin (INS), recombinant hirudin (rHAV2), and recombinant human growth hormone (rhGH), in pulmonary epithelium in vivo. METHODS: Human lung adenocarcinoma A549 cells formed continuous monolayers with growing polycarbonate filters of Transwell plate. Transport studies of macromolecules in the monolayer system were carried out after 6 days in culture. The transport of peptides or proteins with MW 3,400 - 22,000 was studied in cultured human lung adenocarcinoma A549 cell monolayers at different conditions. RESULTS: The results showed that the apparent permeability coefficients (Papp) of these macromolecules across A549 cell monolayers ranged from 2 x 10(-6) to 5 x 10(-6) cm x s(-1) and exhibited good inverse correlation with molecule weight. No concentration, direction and temperature dependence were observed in the permeation of sCT, INS and rHAV2. While the Papp of rhGH in the BA direction (2.25 x 10(-6) cm x s(-1)) was significantly less than that in the reverse direction. The Papp values of rhGH were concentration and temperature independent in the AB direction. CONCLUSION: These findings suggest that the hydrophilic peptides and proteins, salmon calcitonin, insulin, recombinant hirudin, and recombinant human growth hormone used in this study, appeared to penetrate the A549 cell monolayers via a paracellular pathway by passive diffusion mechanism.

Adenocarcinoma↗
PubMed2004

[Effects of the directions of an extraoral retractive force on the displacement of and stress distribution in palate].

OBJECTIVE: The aim of this study was to assess the effects of varying retractive force directions on the displacement of and stress distributions in palate. METHODS: A three-dimensional finite element model of the nasomaxillary complex was created, consisting of 1638 isoparametric elements and 1827 nodes. An extraoral retractive force of 9.8N was applied to the upper canines in 3 different directions, i.e. parallel, 30 degrees upwards and downwards to the functional occlusal plane. Then we investigated the nature of stress distributions, the directions and amounts of displacement in palate by finite element analysis. RESULTS: In the midpalatal suture and transpalatal suture, all displacement directed to bone suture and increased gradually when the retractive force direction ranged from +30 degrees to -30 degrees. In the midmost part of palate, correlation between stress distributions and retractive force directions was not significant. Relatively compressive stresses were induced in the front and middle of the midpalatal suture, whereas nearly no stress was induced in the back. In the lateral part of palate, compressive stresses were nearly equal to tensile stresses in the front, while tensile stresses were induced in the middle and back. Meanwhile, there was no significant correlation between stress distributions and force directions. CONCLUSION: This study showed that the directions of retractive force had obvious effects on displacement but but little effect on stress distributions.

Biomechanical Phenomena↗
PubMed2004

[Relative bioavailability of cyclosporine A-loaded hydroxypropyl methylcellulose phthalate nanoparticles for oral administration in rats].

AIM: To study the preparation of hydroxypropyl methylcellulose phthalate (HPMCP) nanoparticles and compare its pharmacokinetic characteristics with Neoral. METHODS: HPMCP nanoparticles loaded cyclosporine A were prepared by solvent-nonsolvent method. CyA-HP50 nanoparticles, CyA-HP55 nanoparticles and Neoral were orally administered at the dosage of 15 mg x kg(-1) to rats. The CyA concentration in blood were determined by HPLC. Pharmacokinetic parameters were calculated by 3P97 program. RESULTS: The concentration-time data of the three preparations were best fit by two compartment model. The relative bioavailability of CyA-HP50 and CyA-HP55 nanoparticles calculated by the AUC0-72 were 82.3% and 119.6%, bioequivalent to the reference of Neoral. The relative bioavailability of CyA-HP55 nanoparticles was 145.3% of CyA-HP50 nanoparticles. CONCLUSION: CyA HPMCP nanoparticles could be prepared easily and reproducibly. It was found that the oral absorption of CyA can be increased by using the HPMCP nanoparticles.

Administration, Oral↗
PubMed2004

Gene expression profile of degenerated cervical intervertebral disc tissues in rats.

OBJECTIVE: To analyze the gene expression profile of degenerated cervical intervertebral disc of Sprague Dawley rats on a large scale. METHODS: Degenerated models of Sprague Dawley rats of 9 months old (degeneration group, n=9) and normal Sprague Dawley rats of 3 months old (control group, n=9) were prepared, respectively. mRNA was obtained from the cervical intervertebral disc of rats in both groups, respectively, and then labelled by Cy5 and Cy3 fluorescence respectively after reverse transcription to obtain intervertebral disc cDNA probes. cDNA probes were hybridized with BiostarR-40s gene expression profile chips and scanned by laser scanner. The results were treated with portrait analysis, standardization management, and ratio analysis with softwares. RESULTS: Compared with the rats in the control group, 9.6% (381 pieces in total) gene expression changed obviously in the rats in the degeneration group, among which, the gene expression quantities of 171 pieces increased significantly (r=the ratio of the degeneration group to the control group>2.0), 52 pieces of which had certain function. While the gene expression quantities of 211 pieces decreased significantly (r<0.5), 41 pieces of which had certain function. CONCLUSIONS: Gene chip technology can be used to analyze the gene expression profile of degenerated intervertebral disc of rats in parallel, in quantity and on a large scale, which helps to testify the representative genes and protein expression, and plays an important role in clarifying the pathogenesis of degenerated intervertebral disc.

Animals↗
PubMed2004

[Preparation of cyclosporine A pH sensitive nanoparticles and oral pharmacokinetics in rats].

AIM: To study the preparation conditions and its oral pharmacokinetic characteristics of cyclosporine A (CyA) pH sensitive nanoparticles. METHODS: The CyA pH sensitive nanoparticles were prepared by the quasi-emulsion solvent diffusion technique (QESD). Male Sprague-Dawley (SD) rats weighing (250 +/- 20) g were selected and randomly divided into five groups. The bioavailability of CyA from nanoparticles and Neoral microemulsion were assessed at a dose of 15 mg x kg(-1) by gavage. The concentration of CyA in whole blood samples was detected by HPLC to evaluate the relative bioavailability of CyA pH sensitive nanoparticles. RESULTS: The blood concentration profiles of CyA pH sensitive nanoparticles in rats fitted to two compartment models using 3P87 pharmacokinetic calculation program. Compared with the Neoral microemulsion, the relative bioavailability of CyA was 94.8%, 115.2%, 113.6% and 132.5% for CyA-E100, CyA-L100, CyA-L100-55 and CyA-S100 nanoparticles respectively. CONCLUSION: CyA-S100 nanoparticles was shown to significantly improve the oral bioavailability of CyA compared with Neoral microemulsion (P < 0.05). While there were no significant differences between Neoral microemulsion and other CyA pH sensitive nanoparticles. With these results, the potential of pH-sensitive nanoparticles for the oral delivery of CyA was confirmed. Furthermore, this formulation approach can be used to improve the oral bioavailability of other poorly soluble and poorly absorbable drugs.

Administration, Oral↗
PubMed2003

[Development of sustained release tablet of tamoxifen citrate and its in vitro release profile].

OBJECTIVE: To reduce the frequency of administration of tamoxifen citrate so as to improve its bioavailability and patients' compliance. METHODS: HPMC(K4M) was employed as major retarded-release controller. The wetting granulation and directly compressing method was used to produce the sustained release tablet. Then the in vitro release profile was applied as main criteria to evaluate six formulations according to the variation of HPMC(K4M) amount. The concentration of tamoxifen citrate was measured by UV spectrometry. Finally the releasing characteristics of sustained release and conventional tablets were compared to clarify the sustained effect of the former. RESULT: At 278 nm there was no interaction between tamoxifen citrate and the recipients so that it was adopted as the wavelength of determination. The recovery efficiency of this method ranged from 95%-105%. The final formulation could release 86.40% of its loading amount in 12 h and its releasing profile fitted the Zero-order equation well. The percentages of accumulative release in 1 h were 76.81% and 7.08% for sustained release tablet and conventional tablet respectively. CONCLUSION: The sustained release tablet of tamoxifen citrate could demonstrate a continuous and stable releasing profile and last for over 12 h. It has significant retarded effect in comparison with the conventional one and could be a new choice of regimen in its clinical application.

Delayed-Action Preparations↗
PubMed2003

hSGT interacts with the N-terminal region of myostatin.

Myostatin is a new member of the transforming growth factor-beta (TGFbeta) superfamily and functions as a negative regulator of skeletal muscle growth. Herein, we report the identification of a myostatin-associated protein hSGT (human small glutamine-rich tetratricopeptide repeat-containing protein) by using a yeast two-hybrid system. The physical interaction between hSGT and myostatin was further confirmed by pull-down and co-immunoprecipitation experiments. To identify regions involved in the interaction between hSGT and myostatin, we constructed various deletion mutants of hSGT and myostatin, respectively, and examined their interactions in yeast cells. Our results showed that the N-terminal signal peptide of myostatin is essential for its association with hSGT and the C-terminal region of hSGT containing the third TPR motif was indispensable for its interaction with myostatin. Recent studies indicate that hSGT probably functions as a molecular chaperone involved in protein folding and processing. These findings suggest that hSGT may play a role in the regulation of myostatin secretion and activation.

Binding Sites↗
PubMed2003

Gastrointestinal absorption of recombinant hirudin-2 in rats.

To investigate the absorption of recombinant hirudin-2 (rHV2) after oral administration to rats and its possible absorption mechanism, a series of experiments were carried out. The degradation of (125)I-rHV2 in the luminal contents and variant mucosal subcellular fractions, as well as the effect of degradation inhibition of some adjuvant was investigated. The bioavailability of rHV2, with or without degradation inhibitor after oral administration to rats was estimated, whereas the in situ loop test and everted sac experiment were also conducted to understand more about the gastrointestinal absorption of rHV2 in rats. It was demonstrated that the rHV2 was not stable in the luminal contents and subfraction of the intestinal mucosa. Some enzyme inhibitor, such as bacitracin or casein, could inhibit the degradation to certain degrees. The intact rHV2 molecules were found in the rat plasma after oral administration, and the bioavailability varies obviously, dependent on the analytical method. Some of the enzyme inhibitor could enhance the rHV2 oral absorption. There is no site difference on rHV2 absorption in different segments of small intestine. The possible transport mechanism of rHV2 across the gastrointestinal tract is concerned with the endocytosis process.

Administration, Oral↗
PubMed2003

Characterization of AOC2 gene encoding a copper-binding amine oxidase expressed specifically in retina.

We have previously cloned a human, retina-specific, amine oxidase gene (RAO, gene symbol: AOC2), a member of the copper-binding amine oxidase super family. AOC2 shares sequence identity with the human kidney amine oxidase gene (KAO, gene symbol: AOC1) and the vascular adhesion protein-1 gene (VAP-1, gene symbol: AOC3). For further analysis of AOC2, the sequences surrounding the human AOC2 and the complete mouse and partial rat homologue of AOC2 were cloned for characterization. Real-time quantitative PCR, in situ hybridization, and immunohistochemistry were performed to determine the specific expression of AOC2 in the mouse retina and especially in the retinal ganglion cells. Our results demonstrated that the copper-binding motif and the enzyme active site of AOC1 and AOC3 were both conserved in mouse AOC2. The human and mouse AOC2 was flanked by two genes, the Psme3 gene for PA-28 gamma subunit and, surprisingly, the AOC3 gene. Rat AOC2 contained a stop codon that terminated the peptide length to 127 amino acids. The presence of human and rat AOC pseudogene in this region, in addition to the tandemly positioned two AOC genes, indicates the possibility of successful AOC3 replication to retina-specific AOC2 for human and mouse but unsuccessful for rat.

Amine Oxidase (Copper-Containing)↗
PubMed2003

Liquid chromatography determination of 10-hydroxycamptothecin in human serum by a column-switching system containing a pre-column with restricted access media and its application to a clinical pharmacokinetic study.

A simple, rapid, sensitive column-switching HPLC method is described for the analysis of the 10-hydroxycamptothecin (HCPT) in human serum. A pre-column containing restricted access media (RAM) is used for the sample clean-up and trace enrichment and is combined with a C18 column for the final separation. The analytical time is 8 min. The HCPT is monitored with fluorescence detector, excitation and emission wavelengths being 385 and 539 nm, respectively. There is a linear response range of 1-1000 ng/ml with correlation coefficient of 0.998 while the limit of quantification is 0.1 ng/ml. The intra-day and inter-day variations are less than 5%. This analytic procedure has been applied to a pharmacokinetic study of HCPT in clinical patients and the pharmacokinetic parameters of one-compartment model are calculated.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Superoxide, H2O2, and iron are required for TNF-alpha-induced MCP-1 gene expression in endothelial cells: role of Rac1 and NADPH oxidase.

Reactive oxygen species (ROS) play an important but not yet fully defined role in the expression of inflammatory genes such as monocyte chemoattractant protein (MCP)-1. We used complementary molecular and biochemical approaches to explore the roles of specific ROS and their molecular linkage to inflammatory signaling in endothelial cells. Adenovirus-mediated expression of superoxide dismutase and catalase inhibited TNF-alpha-induced MCP-1 gene expression, suggesting important roles of superoxide (O(2)(-).) and H(2)O(2) in MCP-1 gene activation. In addition, the iron chelator 1,2-dimethyl-3-hydroxypyridin-4-one and the hydroxyl radical scavengers dimethylthiourea and dimethyl sulfoxide inhibited TNF-alpha-induced MCP-1 expression, suggesting important roles of iron and hydroxyl radicals in inflammatory signal activation. In contrast, scavenging of peroxynitrite with 5,10,15,20-tetrakis-(4-sulfonatophenyl)prophyrinato iron (III) chloride had no effect on TNF-alpha-induced MCP-1 expression. Inhibition of NADPH oxidase, the major oxidase responsible for O(2)(-). generation, with diphenylene iodonium suppressed TNF-alpha-induced MCP-1 mRNA accumulation. Rac1 is an upstream signaling molecule for the activation of NADPH oxidase and O(2)(-). generation. Expression of dominant negative N17Rac1 by adenovirus suppressed TNF-alpha-induced MCP-1 mRNA levels and MCP-1 protein secretion. Expression of N17Rac1 inhibited TNF-alpha-induced MCP-1 and NF-kappaB transcriptional activity. These data suggest that ROS such as superoxide and H(2)O(2) derived from Rac1-activated NADPH oxidase mediate TNF-alpha-induced MCP-1 expression in endothelial cells.

Antineoplastic Agents↗