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Biomedical subjects

Jin Sun

Publications and source records attributed to Jin Sun.

At least 37 records · Page 2Linked to original sources
PubMed2005

Impact of release characteristics of sinomenine hydrochloride dosage forms on its pharmacokinetics in beagle dogs.

AIM: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride (SM.HCl) on its pharmacokinetics in beagle dogs. METHODS: The in vitro release behavior of two SM.HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM.HCl pharmacokinetics was investigated and compared. RESULTS: The optimal SM.HCl sustained-release formulation was achieved by mixing slow- and rapid-release pellets (9:1, w/w). The SM.HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs 68.7%. From a pharmacokinetic standpoint, the 24-h SM.HCl sustained-release pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67+/-0.52 h vs 9.83+/-0.98 h and the Cmax being 1 334.45+/-368.76 ng/mL vs 893.12+/-292.55 ng/mL, respectively. However, the AUC(0-tn) of two SM.HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM.HCl percentage absorption in vivo and the cumulative percentage release in vitro. CONCLUSION: The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves.

Administration, Oral↗
PubMed2005

Blockade of L-type voltage-gated Ca channel inhibits ischemia-induced neurogenesis by down-regulating iNOS expression in adult mouse.

Neurogenesis in the adult mammalian hippocampus may contribute to repairing the brain after injury. The signals that regulate neurogenesis in the dentate gyrus following ischemic stroke insult are not well known. We have previously reported that inducible nitric oxide synthase (iNOS) expression is necessary for ischemia-stimulated neurogenesis in the adult dentate gyrus. Here, we show that mice subjected to 90 min of middle cerebral artery occlusion (MCAO) significantly increased the number of new neurons and up-regulated iNOS expression in the dentate gyrus. Blockade of the L-type voltage-gated Ca(2+) channel (L-VGCC) prevented neurogenesis in the dentate gyrus and subventricular zone (SVZ), and down-regulated iNOS expression in the dentate gyrus after cerebral ischemia. This study suggests that Ca(2+) influx through L-VGCC is involved in ischemia-induced neurogenesis by up-regulating iNOS expression.

Animals↗
PubMed2005

Validation of an HPLC method for the determination of scutellarin in rat plasma and its pharmacokinetics.

A validated HPLC method was developed for the quantification of scutellarin in rat plasma using a liquid-liquid extraction and an ultraviolet detection. Chromatographic separation of scutellarin in plasma was performed on a C18 column, with a mobile phase of acetonitrile-water (23:77, v/v), adjusted to pH 2.5 with 1M phosphoric acid, and rutin was used as an internal standard. The calibration curve was linear over the range 0.1-100 microg/ml in rat plasma. The average extraction recoveries were 85.9+/-8.9, 71.0+/-4.6, 72.7+/-1.2% (n=3) at concentrations of 0.1, 2, 100 microg/ml, respectively, and the within-day and between-day precisions were less than 15%. After intravenous administration to rats over the doses range of 10-40 mg/kg, the plasma concentration-time curve of scutellarin was best conformed to three-compartment open model. The AUC of scutellarin was proportional to dose, and the systemic clearance (Cl), elimination half-life (t1/2beta) and apparent volume of distribution (Vc) were not significantly different among the three doses, suggestive of the linear pharmacokinetics characteristic of scutellarin after intravenous administration.

Animals↗
PubMed2005

Impact of pharmaceutical dosage forms on the pharmacokinetics of roxithromycin in healthy human volunteers.

OBJECTIVES: The impact of two different pharmaceutical preparations on the pharmacokinetics of roxithromycin was investigated in healthy human volunteers. METHODS: The degradation kinetics and products of roxithromycin were investigated in simulated gastric fluid and simulated intestinal fluid. Two oral dosage forms of roxithromycin were employed: enteric-coated pellets and dispersible tablets. RESULTS: The degradation half-time of roxithromycin in simulated gastric fluid was 0.23 h, and three main degradation products were characterized. In contrast, roxithromycin was stable in simulated intestinal fluid and remained unchanged after a 1.00 h incubation. The roxithromycin enteric-coated pellets exhibited higher bioavailability and a more potent serum antibacterial activity than the dispersible tablets. CONCLUSIONS: The type of oral dosage forms of roxithromycin altered its pharmacokinetics. Whether or not this affects the in vivo antibacterial efficacy requires further study.

Adult↗
PubMed2005

Synthesis and properties of polysaccharide prodrugs of 5-aminosalicylic acid as potential colon-specific delivery systems.

The drug release of the polymer prodrugs of 5-aminosalicylic acid (5-ASA) was not only dependent on the property of the polymers but also dependent on the solubility of the prodrugs. We prepared several polysaccharide prodrugs of 5-ASA to examine the effect of solubility of prodrugs on the release characteristics of 5-ASA in the gastrointestinal contents of rats. The amide prodrug, chitosan-5-ASA (ChT-5-ASA), did not release the 5-ASA in the cecal and colonic contents. The ester prodrugs, hydroxypropyl cellulose-5-ASA (HPC-5-ASA), being poor solubility in 0.05mol/l acetic acid solution also did not release the 5-ASA in any of gastrointestinal contents of rats. Whereas the 5-ASA release from cyclodextrins-5-ASA (CyDs-5-ASA) in cecal and colonic contents was significantly higher than that in stomach and small intestine contents. And furthermore, with the decrease in the degree of substitution, the solubility of CyD-5-ASA increased, and the release of 5-ASA in the gastrointestinal contents was also higher at the same time interval of incubation. When the ratio of cyclodextrin (CyD) and 5-formylaminosalicylic acid (5-fASA), a precursor of 5-ASA prodrugs, was 1:10, CyD-5-ASA was very slightly soluble, and no release of 5-ASA was observed within 48h in gastrointestinal contents. The present results suggested that the ester prodrugs of 5-ASA with certain solubility could release 5-ASA in the cecal and colonic contents of rat.

Animals↗
PubMed2005

Steroid cell tumors, not otherwise specified (NOS), in an accessory ovary: a case report and literature review.

BACKGROUND: Accessory ovaries are uncommon congenital abnormalities of the female reproductive tract. Steroid cell tumors at accessory ovaries are proportionately even rare. CASE: This 30-year-old woman had an accessory ovarian tumor attached to the infundibulum of the right fallopian tube which was solid and gross pathologically and microscopically showed the appearances of steroid cell tumor, NOS, a benign entity. CONCLUSION: We report the first case of an accessory ovarian steroid cell tumor, NOS, which attached to the infundibulum of fallopian tube.

Adult↗
PubMed2005

Multihydroxylated [Gd@C82(OH)22]n nanoparticles: antineoplastic activity of high efficiency and low toxicity.

[Gd@C82(OH)22]n particles (22 nm in a saline solution) of a dose level as low as 10(-7) mol/kg exhibit a very high antineoplastic efficiency ( approximately 60%) in mice. A dose increment of 1 x 10(-7) mol/kg increases the tumor inhibition rate 26%. [Gd@C82(OH)22]n particles have a strong capacity to improve immunity and interfere with tumor invasion in normal muscle cells, nearly without toxicity in vivo and in vitro. Unlike conventional antineoplastic chemicals, the high antitumor efficiency of nanoparticles is not due to toxic effects to cells because they do not kill the tumor cells directly and only about 0.05% of the used dose is found in the tumor tissues. Results suggest that fullerene derivatives with proper surface modifications and sizes may help realize the dream of tumor chemotherapeutics of high-efficacy and low-toxicity.

Animals↗
PubMed2005

Synergistic and additive properties of the beta-globin locus control region (LCR) revealed by 5'HS3 deletion mutations: implication for LCR chromatin architecture.

Deletion of the 234-bp core element of the DNase I hypersensitive site 3 (5'HS3) of the locus control region (LCR) in the context of a human beta-globin locus yeast artificial chromosome (beta-YAC) results in profound effects on globin gene expression in transgenic mice. In contrast, deletion of a 2.3-kb 5'HS3 region, which includes the 234-bp core sequence, has a much milder phenotype. Here we report the effects of these deletions on chromatin structure in the beta-globin locus of adult erythroblasts. The 234-bp 5'HS3 deletion abolished histone acetylation throughout the beta-globin locus; recruitment of RNA polymerase II (pol II) to the LCR and beta-globin gene promoter was reduced to a basal level; and formation of all the 5' DNase I hypersensitive sites of the LCR was disrupted. The 2.3-kb 5'HS3 deletion mildly reduced the level of histone acetylation but did not change the profile across the whole locus; the 5' DNase I hypersensitive sites of the LCR were formed, but to a lesser extent; and recruitment of pol II was reduced, but only marginally. These data support the hypothesis that the LCR forms a specific chromatin structure and acts as a single entity. Based on these results we elaborate on a model of LCR chromatin architecture which accommodates the distinct phenotypes of the 5'HS3 and HS3 core deletions.

Acetylation↗
PubMed2005

Study on the role of hepatic first-pass elimination in the low oral bioavailability of scutellarin in rats.

In the present study, we compared the systemic exposure of scutellarin following intraportal with intravenous administration to understand the contribution of presystemic hepatic elimination to the low oral bioavailability. Results showed that the hepatic first-pass elimination of scutellarin played an insignificant role in the presystemic elimination of orally administered scutellarin. Moreover, our results suggested that the site of first pass extraction was not the liver, but the gastrointestinal tract.

Animals↗
PubMed2005

[Immobilized artificial membrane chromatography and its application in profiling the drug membrane transport].

Immobilized artificial membrane chromatography (IAMC) is a system of covalently bonding monolayer of phospholipid analogs onto the solid surface of silica particles, thus establishing the emulating process of drug-cellular membrane interactions in terms of chromatographic method, and is applied to profile the drug membrane permeability and biological activity. IAMC phases prepared from phosphocholine analogues closely mimic the surface of the biological cell membrane, and the capacity factor of drugs can be used to predict the interaction between drug molecules and cell membranes. IAMC, compared with n-octanol/water, liposome/water and ODS chromatography, can simulate other forces besides hydrophobic interaction. IAMC is getting more and more profound research because of its convenience and high efficiency. The primary screening by means of IAMC in the early stage of drug development would effectively lower failure in the preclinical and clinical development, since efficacy and safety are related in the larger part to membrane permeability. The interaction mechanism of drug-IAM and its profiling in membrane transport are reviewed.

Chromatography↗
PubMed2005

Rapid and sensitive determination of indapamide in human blood by liquid chromatography with electrospray ionization mass spectrometric detection: application to a bioequivalence study.

A rapid and sensitive method using liquid chromatography with electrospray ionization mass spectrometric detection was developed and validated for the determination of indapamide in human blood. Blood samples were extracted with n-hexane-dichloromethane (1:1, v/v) and separation was performed on a Symmetry C18 column (150 x 3.9 mm i.d., 5 microm) with the mobile phase consisting of acetonitrile-water (60:40, v/v). Indapamide and internal standard (propylparaben) were detected by negative electrospray ionization and selected ion recording (SIR) at m/z 364 for indapamide and m/z 179 for propylparaben. This method has a lower limit of quantification (LLOQ) 2.0 microg/L with a linear calibration range of 2.0 microg/L to 120 microg/L. The method showed excellent reproducibility with an inter- and intra-assay precision of < 9.4% (% RSD), as well as excellent accuracy with an inter- and intra-assay accuracy of between 98.0 and 102%. Furthermore, the method was successfully applied to a bioequivalence study in which 20 healthy volunteers received a single oral dose of 3 mg reference and test sustained-release indapamide formulations, in an open, two-period, randomized crossover protocol. The maximum blood concentrations (C(max)) were 60.3 +/- 22.6 microg/L and 57.6 +/- 18.7 microg/L at 13.1 +/- 6.9 h and 18.3 +/- 7.4 h, the times to reach the peak concentration (T(max)), for the test and reference tablets, respectively. The relative bioavailability of the test tablets was 110.1 +/- 34.5%, compared with the reference tablets. There were no statistically significant differences in the main pharmacokinetic parameters, and the two formulations were judged to be bioequivalent.

Antihypertensive Agents↗
PubMed2004

Differences of globin transgene expression in stably transfected cell lines and transgenic mice.

Previous studies demonstrated that DNase I hypersensitive site -40 (HS-40) of the alpha-globin locus is capable of greatly enhancing expression of a hybrid beta/gamma-globin transcriptional unit in plasmid-transfected murine erythroleukemia (MEL) cells. However, as reported here, this same gamma-globin gene expression cassette was only transcribed at trace amounts in erythroid cells of transgenic mice. This lack of expression was not directly attributable to the beta/gamma-globin transcriptional unit, since this same unit linked to a composite beta-globin locus control region was expressed at high levels in transgenic mice. This lack of expression was also not directly attributable to chromosomal position effects, since addition of chromatin insulators failed to increase the frequency of expression. DNase I hypersensitivity and chromatin immunoprecipitation assays demonstrated that the lack of expression was correlated with a closed chromatin structure. We hypothesize that transgenes undergo dynamic changes in chromatin conformation following chromosomal integration and that the discrepant results reported here can be attributed to the relatively high level of chromatin remodeling that occurs in the transgenic mouse model, coupled with the relative inability of the HS-40 element to maintain an open chromatin state under such conditions.

Animals↗
PubMed2004

Time- and pH-dependent colon-specific drug delivery for orally administered diclofenac sodium and 5-aminosalicylic acid.

AIM: To investigate Time- and pH-dependent colon-specific drug delivery systems (CDDS) for orally administered diclofenac sodium (DS) and 5-aminosalicylic acid (5-ASA), respectively. METHODS: DS tablets and 5-ASA pellets were coated by ethylcellulose (EC) and methacrylic acid copolymers (Eudragit L100 and S100), respectively. The in vitro release behavior of the DS coated tablets and 5-ASA coated pellets were examined, and then in vivo absorption kinetics of DS coated tablets in dogs were further studied. RESULTS: Release profile of time-dependent DS coated tablets was not influenced by pH of the dissolution medium, but the lag time of DS release was primarily controlled by the thickness of the coating layer. The thicker the coating layer, the longer the lag time of DS release is. On the contrary, in view of the pH-dependent 5-ASA coated pellets, 5-ASA release was significantly governed by pH. Moreover, the 5-ASA release features from the coated pellets depended upon both the combination ratio of the Eudragit L100 and S100 pH-sensitive copolymers in the coating formulation and the thickness of the coating layer. The absorption kinetic studies of the DS coated tablets in dogs demonstrated that in vivo lag time of absorption was in a good agreement with in vitro lag time of release. CONCLUSION: Two types of CDDS, prepared herein by means of the regular coating technique, are able to achieve site-specific drug delivery targeting at colon following oral administration, and provide a promising strategy to control drug release targeting the desired lower gastrointestinal region.

Administration, Oral↗
PubMed2004

Novel lanthanide(II) complexes supported by carbon-bridged biphenolate ligands: synthesis, structure and catalytic activity.

[Ln[N(SiMe3)2]2(THF)2](Ln = Sm, Yb) reacts with 1 equiv. of carbon-bridged biphenols, 2,2'-methylene-bis(6-tert-butyl-4-methylphenol)(L1H2) or 2,2'-ethylidene-bis(4,6-di-tert-butylphenol)(L2H2), in toluene to give the novel aryloxide lanthanide(II) complexes [[LnL1(THF)n]2](Ln = Sm, n = 3 (1); Ln = Yb, n = 2 (2)) and [[LnL2(THF)3]2](Ln = Sm (5); Ln = Yb (6)) in quantitative yield, respectively. Addition of 2 equiv. of hexamethylphosphoric triamide (HMPA) to a tetrahydrofuran (THF) solution of 1, 2 and 5 affords the corresponding HMPA-coordinated complexes, [[LnL1(THF)m(HMPA)n]2(THF)y](Ln = Sm, n = 2, m = 0, y = 2 (3); Ln = Yb, m = 1, n = 1, y = 6 (4)) and [[SmL2(HMPA)2]2](7) in excellent yields. The single-crystal structural analyses of 3, 4 and 7 revealed that these aryloxide lanthanide(II) complexes are dimeric with two Ln-O bridges. The coordination geometry of each lanthanide metal can be best described as a distorted trigonal bipyramid. Complexes 1-3, 5 and 7 can catalyze the ring-opening polymerization of epsilon-caprolactone (epsilon-CL), and 1-3, along with 5 show moderate activity for the ring-opening polymerization of 2,2-dimethyltrimethylene carbonate (DTC) and the copolymerization of epsilon-CL and DTC to give random copolymers with high molecular weights and relatively narrow molecular weight distributions..

Journal Article↗
PubMed2004

Multidrug resistance P-glycoprotein: crucial significance in drug disposition and interaction.

This article reviews recent advances in our understanding of the structure, drug interaction mechanism, and substrate molecular requirements of P-glycoprotein (P-gp) and its emerging crucial role in drug disposition and the modulation of drug interaction. In view of its wide localization in normal tissues, the broad variety of structurally and functionally unrelated substrates of P-gp, and its ATP-dependent outward-oriented transport, P-gp actively participates in intestinal secretion, blood-tissue barriers, and biliary and renal excretions for many exogenous substrates, and also performs a protective role to prevent entry of xenobiotics. Moreover, the importance of P-gp-mediated drug interactions in clinical practice can hardly be underestimated, since it may result in severe side effects, such as digitalis drug interaction. Polymorphism or single nucleotide polymorphism (SNP) associated with P-gp may exert a significant effect on the pharmacokinetic behavior of its substrates, a fact which has major clinical implications and suggests careful dose adjustment for individual treatment. Moreover, dietary components and pharmaceutical excipients may modulate P-gp activity, and as a result affect in vivo drug disposition and therapeutic efficacy; examples include grapefruit juice, Pluronic P85, PEG 300, etc. In summary, it should be emphasized that P-gp is an integral component in the process of drug discovery, development strategy,

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

[Low-dose granulocyte colony-stimulating factor combined with granulocyte-macrophage colony-stimulating factor for mobilizing peripheral CD34+ hematopoietic progenitor cells].

OBJECTIVE: To study the efficacy of combined use of low-dose granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in mobilizing hematopoietic stem/progenitor cells. METHODS: Twenty adult patients with malignant hematologic diseases were paired using statistical methods, and the 10 pairs were divided into 2 equal groups. For non-Hodgkin lymphoma, the treatment regimen adopted intravenous infusion of cytoxan (2 g/d for 1 or 2 d) and VP16 (0.2 g/d for 1 to 3 d), while for acute non-lymphocytic leukemia, Ara-C (2 g/d for 1 to 3 d) and VP16 (0.2 g/d for 1 to 3 d) were used. When the while blood cell count (WBC) was below 1.0 x10(9)/L, G-CSF and GM-CSF were administered subcutaneously at the same dose of 2.5 microg/d.kg in the 10 patients in the experimental group, while the patients in the control group received only 5 microg/d.kg G-CSF, both for 5 to 6 d. After WBC>5.0 x 10(9)/L, the peripheral blood mononuclear cells (PBMNC) were separated by CS-3000 pluse separator and CD34+ cells were determined by flow cytometry. RESULTS: The purity of the isolated PBMNC was 95%-99%. In the experimental group, the mean number of CD34+ cells acquired was 9.4 x 10(6)/kg ranging from 8.4 x 10(6) to 10.2 x 10(6)/kg, and granulocyte-macrophage colony-forming unit (CFU-GM) was 42.4 x 10(4)/kg on average ranging from 21.9 x 10(4) to 72.8 x 10(4)/kg, as compared with 4.8 x 10(6)/kg [(4.1-8.3) x10(6)/kg] for CD34+ cells and 28.1 x 10(4)/kg [(7.1-60.2) x 10(4)/kg] for CFU-GM in the control group (P<0.05). No obvious difference was observed between the two groups in terms of the adverse effects of the treatment (P>0.05). CONCLUSION: Combined use of G-CSF and GM-CSF can be more effective than the exclusive use of GM-CSF for mobilizing CD34+ cells.

Adult↗