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Biomedical subjects

Jin Sun

Publications and source records attributed to Jin Sun.

49 records · Page 3Linked to original sources
PubMed2004

Organ distribution of 5-fluorouracil loaded gelatine microspheres in mice.

The aim of this study was to investigate the organ distribution characteristics of 5-fluorouracil (5-Fu) loaded crosslinked gelatine microspheres (5-Fu-MS) after intravenous (i.v.) injection compared to 5-Fu solution in mice, and to evaluate the targetability of 5-Fu-MS. The concentrations of 5-Fu in mice plasma, heart, liver, lung, kidney, spleen and brain were determined by HPLC. The parameters drug targeting index C(e), time-averaged relative drug exposure values r(e), drug targeting efficiency t(e), and drug distributed to target-tissue (%) were used to evaluate the targetability of the 5-Fu-MS delivery system. The results showed that the concentration of 5-Fu in the lung was significantly higher than after application of 5-Fu solution, and that the maximum concentration of 5-Fu, 72.8 microg x g organ(-1), was reached in the lung at 15 min after i.v. administration. As for 5-Fu-MS, r(e) was calculated to be 2.2, and t(e) was considerably higher than after application of 5-Fu in solution. Furthermore, the percentage of drug distributed to the lung was 2 times as high as after application in solution. Accordingly, 5-Fu-MS were capable of effectively delivering 5-Fu to the lung and possessed specific targetability towards the lung compared to 5-Fu solution.

Algorithms↗
PubMed2003

Protonation equilibrium and lipophilicity of olamufloxacin (HSR-903), a newly synthesized fluoroquinolone antibacterial.

This study was performed to characterize the protonation equilibrium at the molecular level and pH-dependent lipophilicity of olamufloxacin. The deprotonation fraction of the carboxyl group as a function of pH was specifically calculated at the critical wavelength 294 nm, where UV pH-dependent absorbance of olamufloxacin was independent of the ionized state of the aminopyrrolidinyl amino group but heavily depended on that of the carboxyl moiety. Accordingly, micro-protonation equilibrium could be described using a nonlinear least-squares regression program MULTI. In contrast, macro-protonation equilibrium was depicted at most wavelengths where olamufloxacin absorbance was influenced by ionized states of both proton-binding groups, results coinciding with the former. Furthermore, distribution features of four microspecies in aqueous phase were assessed. The apparent partition coefficient versus pH profile of olamufloxacin showed a parabolic curve in n-octanol/buffer system which reached peak near pH 8, agreeing with the above determined isoelectric point (pI). Ion-pair effect was observed for olamufloxacin under an acidic condition, eliciting experimental values higher than those theoretically calculated, which was similar to ciprofloxacin but not levofloxacin due to amino group type. Moreover, olamufloxacin was moderately lipophilic in comparison with other quinolones, with an apparent partition coefficient of 1.95 at pH 7.4.

Anti-Bacterial Agents↗
PubMed2003

Altered expression of genes involved in hepatic morphogenesis and fibrogenesis are identified by cDNA microarray analysis in biliary atresia.

Biliary atresia (BA) is characterized by a progressive, sclerosing, inflammatory process that leads to cirrhosis in infancy. Although it is the most common indication for liver transplantation in early childhood, little is known about its etiopathogenesis. To elucidate factors involved in this process, we performed comprehensive genome-wide gene expression analysis using complementary DNA (cDNA) microarrays. We compared messenger RNA expression levels of approximately 18,000 human genes from normal, diseased control, and end-stage BA livers. Reverse-transcription polymerase chain reaction (RT-PCR) and Northern blot analysis were performed to confirm changes in gene expression. Cluster and principal component analysis showed that all BA samples clustered together, forming a distinct group well separated from normal and diseased controls. We further identified 35 genes and ESTs whose expression differentiated BA from normal and diseased controls. Most of these genes are known to be associated with cell signaling, transcription regulation, hepatic development, morphogenesis, and fibrogenesis. In conclusion, this study serves to delineate processes that are involved in the pathogenesis of BA.

Adolescent↗
PubMed2003

Distribution characteristics of grepafloxacin, a fluoroquinolone antibiotic, in lung epithelial lining fluid and alveolar macrophage.

The purpose of this study was to investigate the distribution of Grepafloxacin (GPFX), a new quinolone antimicrobial agent, in the lung epithelial lining fluid (ELF) and the alveolar macrophage (AM) in rats, which are potential infection sites in respiratory tract infections. We also aimed to clarify the mechanism governing the transferability of GPFX into the alveolus compartment from a kinetic point of view. The AUC ratios of ELF/plasma and AM/plasma after the oral administration of GPFX were 5.69 +/- 1.00 and 352 +/- 57, respectively, which were several-fold greater than those of ciprofloxacin (CPFX). Pharmacokinetic analyses of time profiles of GPFX concentrations in ELF and AM revealed that the influx clearance from plasma to ELF across the alveolar barrier is 5-fold greater than the efflux clearance from ELF. In addition, the permeability of GPFX across the cultured AM cell membrane was 7-fold and 11-fold greater than that of levofloxacin (LVFX) and CPFX, respectively. The extent of intracellular binding to AM cells (expressed as a constant (alpha)) was the greatest for GPFX, followed by CPFX and LVFX. There was a significant correlation between the alpha value and the partitioning to the immobilized artificial membrane (IAM) column, which consists of phospholipid residues covalently bound to silica. These results suggest that GPFX is highly distributed in ELF and AM, and that the high transferability of GPFX into ELF may be attributable to the existence of asymmetrical transport across the alveolar barrier. In addition, it was suggested that both rapid permeability across the AM cell membrane and avid binding to the membrane phospholipids may be responsible for the high accumulation of GPFX in AM.

Journal Article↗
PubMed2003

[Autologous adoptive immunotherapy without destruction of infected cells during the treatment of chronic hepatitis B].

OBJECTIVES: To investigate the profile of liver histological damage after autologous adoptive immunotherapy with cytokine-induced killer cells (CIK cells) in patients with chronic hepatitis B (CHB). METHODS: 16 CHB patients were randomly enrolled and received autologous adoptive immunotherapy, then followed up 52 weeks. Liver samples were taken from the patients to evaluate the degree of inflammation and fibrosis. The markers of hepatitis B virus and liver function were also detected. RESULTS: 4 patients had two liver-biopsied samples before therapy and after 52 weeks follow-up. One patient's histological assessment revealed a significant improvement in intralobular necroinflammation (G2 --> G1) and fibrosis (S2 --> S1). The others failed to show obvious changes in liver histology. After 10 days culture in vitro, phenotypic characterization of CIK cells changed significantly by flow cytometry. The percentage of CD4+ cells decreased gradually, while the percentage of CD8+ cells increased from 20% to 60% - 80%. After 52 weeks follow-up, HBV DNA was negative (HBV DNA<4pg/ml in serum) in 6 out of 14 patients. The rates of both HBeAg/anti-HBe seroconversion and alanine aminotransferase normalization were 42.86%(6/14). There was no HBsAg/anti-HBs seroconversion. There was few severe treatment-related adverse events. CONCLUSION: Autologous adoptive immunotherapy doesn't induce the damage of liver histology in chronic hepatitis B patients, which inhibits hepatitis B virus replication by a certain noncytotoxic mechanism.

Adolescent↗
PubMed2003

[Changes of peripheral blood CD45RA+ cells after hematopoietic stem cell transplantation: evaluation with four-color flow cytometry].

OBJECTIVE: To investigate the alteration of peripheral blood naive T cells in adult patients after hematopoietic stem cell transplantation (HSCT). METHODS: Peripheral blood samples were collected from 49 patients requiring stem cell transplantation before and 15, 30, 90, and 180 d after transplantation, respectively. Dynamic changes of CD4(+)CD45RA(+)/CD8(+)CD45RA(+) cell counting were measured using flow cytometry. RESULTS: Flow cytometry results of 90 samples showed that CD8(+)CD45RA(+) cells recovered to normal level 30 d after transplantation, whereas CD4(+)CD45RA(+) cells remained low and kept a slow pace of gradual increase over the 6 months following the transplantation. More rapid recovery of the transport and regeneration function of the thymus cells was achieved in patients receiving hematopoietic stem cell autotransplant than in those with allotransplant. CONCLUSION: Measurement of the changes of CD4(+)CD45RA(+)/CD8(+)CD45RA(+) cell ratio using flow cytometry may provide insights into the molecular picture of the thymus regeneration function in association with immune reconstruction process in patients after stem cell transplantation. The number of newly generated T cells transported from the thymus can be a putative marker of immune reconstruction after transplantation.

Adolescent↗
PubMed2003

[Autogeneic peripheral blood hemopoietic stem cell transplantation for chronic myeloid leukemia with imatinib mesylate-induced negative Philadelphia chromosome].

OBJECTIVE: To study the possibility of curing chronic myeloid leukemia with autogeneic hemopoietic stem cell transplantation in patients with negative Philadelphia (Ph) chromosome induced by imatinib mesylate (STI 571) treatment. METHODS: Two patients with chronic myeloid leukemia in chronic phase, who had 90% Ph chromosome-positive cells and bcr/abl fusion gene-positive cells as shown by interphase fluorescence in situ hybridization (I-FISH), failed to respond favorably to interferon-alpha therapy in the treatment courses of 7 and 8 months, respectively. Treatment with STI 571 at a daily dose of 300 to 400 mg for 5 months to 8 months was subsequently implemented, after which the Ph chromosome and bcr/abl fusion genes became normal in detection for 3 times. Peripheral blood haemopoietic stem cell mobilization was then initiated by intravenous injection of cytarabine (2.0 g/d) for 3 days, etoposide (0.2 g/d) for 3 d and cyclophosphamide (1.0 g/d) for one day. When the white blood cell was below 1.0x10(9)/L, the G-CSF (300 microg/d) was administered subcutaneously for 5 or 6 d, and the peripheral blood mononuclear cells were collected by CS3000 Plus blood cell separator. The percentage of bcr/abl fusion gene-positive cells among CD34(9) cells enriched by MiniMAC ranged from 11% to 14%. After 3 or 4 weeks, the patients received total body irradiation at 9 Gy given in 2 fractions, with intravenous injection of cyclophosphamide (60 mg/kg daily) and etoposide (300 mg/d) for 2 d. On the day of transplantation, the collected mononuclear cells were 4.17x10(8)/kg and 3.9x10(8)/kg, with CD34(+)/ cells reaching 4.89x10(6)/kg.b.w and 4.89x10(6)/kg. CsA was also used since day -1 to day +13 of the transplantation for prevention of graft-versus-host disease. G-CSF was administrated daily at the dose of 300 microg subcutaneously from day +3 to +12. RESULTS: After the transplantation, the absolute neutrophil count (ANC) took a mean of 11 d to exceed 0.5x10(9)/L in these two patients, and 19 and 21 d, respectively, were needed for the platelet count to exceed 20x10(9)/L. The two patients showed cytogenetic relapse at 120 and 300 d after the transplantation, respectively. CONCLUSION: Autogeneic peripheral blood stem cells transplantation after Ph chromosome is negative in patients with chronic myeloid leukemia, who receive STI 571 treatment, may also relapse, and more radical elimination of Ph chromosome-positive cells is needed.

Adult↗
PubMed2003

[Comparative study of lipophilicity from immobilized artificial chromatography and n-octanol/buffer systems].

AIM: To compare lipophilicity measuring scale stemmed from immobilized artificial membrane chromatography and n-octanol/buffer systems. METHODS: A test set consisted of 27 structurally diverse compounds. The lipophilicity of these were evaluated by both immobilized artificial membrane chromatography (IAMC) and n-octanol/buffer systems, which were expressed as lg kIAM and lg DO/W,7.4, respectively. RESULTS: With regard to each individual group, good correlation coefficient (r2) over 0.81 was obtained (0.82 for acid; 0.88 for neutral, 0.81 for base and 0.92 for ampholyte, respectively). However, a smaller r2 (0.62) was acquired for all compounds studied than that of each individual group. CONCLUSION: IAMC and n-octanol/buffer systems were shown to be different in lipophilicity.

Buffers↗
PubMed2003

[Evaluation of interaction between drugs and ordered phospholipid membrane by immobilized artificial membrane chromatography].

AIM: To investigate the interaction between drugs and ordered phospholipid membrane using immobilized artificial membrane chromatography (IAMC). METHODS: IAMC was used to determine the interaction drugs with phospholipid membrane, expressed as membrane affinity (lg kIAM). An n-octanol/buffer system was also employed as the reference hydrophobicity (lg Do/w,7.4). RESULTS: Within the range of used acetonitrile percentages (phi) 0-30% in mobile phase, retention index (lg kIAM) showed excellent correlation with phi. Intercepts of fitted straight lines between lg kIAM and phi were comparable but slopes were much different for the three organic modifiers (acetonitrile, ethanol and methanol). Effects by adding CH2 substituent on lipophilicity difference (delta lg kIAM and delta lg Do/w,7.4) were similar for p-hydroxyl benzoic methyl ester to butyl ester, whereas different for p-hydroxylbenzoic acid to methyl ester. CONCLUSION: IAMC system is a convenient, efficient and rapid tool for determining membrane interaction.

Membranes, Artificial↗
PubMed2002

A novel aryl amide-bridged ladderlike polymethylsiloxane synthesized by an amido H-bonding self-assembled template.

A novel soluble aryl amide-bridged ladderlike polymethylsiloxane (A-LPMS) was synthesized by stepwise coupling polymerization on the basis of amido H-bonding self-assembling template from monomer N,N'-bis(3-methyldiethoxylsilylpropyl)-[4,4'-oxybis(benzyl amide)]. The monomer was prepared in a high yield by the hydrosilylation reaction of template agent N,N'-diallyl-[4,4'-oxybis(benzyl amide)] with methyldiethoxysilane in the presence of dicyclopentadienylplatinum dichloride (Cp(2)PtCl(2)) as catalyst. A variety of techniques including (1)H NMR, (13)C NMR, (29)Si NMR, FTIR, XRD, DSC, and, especially, static and dynamic light scattering and viscosimetry were combined to confirm the presence of the ordered ladderlike structure of polymer A-LPMS.

Journal Article↗
PubMed2002

Determination of lipophilicity of two quinolone antibacterials, ciprofloxacin and grepafloxacin, in the protonation equilibrium.

The objective of this study was to compare protonation equilibrium and lipophilicity of two quinolone antibacterials, grepafloxacin (GPFX) and ciprofloxacin (CPFX), in order to give an insight into effects on the physicochemical properties by slight structural motifs. The protonation equilibrium was investigated by a spectrophotometry. Macro- and micro-dissociation constants were simultaneously determined, based on nonlinear regression analysis using the MULTI program, and then microspecies distribution could be described accordingly. Zwitterionic microspecies predominated at isoelectrical point (pI) for both drugs, and the concentration ratio of neutral to zwitterionic forms was near 4-fold greater for GPFX than that for CPFX. The apparent partition coefficient (D(O/B,pH)) versus pH profiles had the shape of a parabolic curve in an n-octanol/buffer system, and reached the maximum around pI for both, respectively. Moreover, two introduced methyl groups in GPFX increased not only intrinsic lipophilicity but also neutral microspecies fraction relative to CPFX, and D(O/B,pH) of GPFX was consequently far higher than that of CPFX. The results emphasized that there were significant differences in protonation equilibrium and lipophilicity between GPFX and CPFX, which conduced to explaining their different behavior in terms of antibacterial activities and pharmacokinetics.

Anti-Infective Agents↗
PubMed2002

Interactions between quinolone antibiotics and phospholipid membrane for prediction of alveolar macrophage uptake in vitro.

AIM: To compare the effectiveness of the different parameters for predicting alveolar macrophage (AM) uptake, interactions between quinolones, including two amphipathic bases, and phospholipid membrane were evaluated by three different membrane-like systems. METHODS: AM cells were isolated, cultured as confluent monolayers, then incubated with drug solution at 37 degrees C. At designated time points, uptake was terminated by aspirating solution, followed by rinsing, cell lysis, a nd analysis of drug and protein concentrations. Immobilized artificial membrane (IAM) chromatography and liposome/buffer system were used to determine interactions with phospholipid membrane, expressed as lipophilicity indices, lg k(IAM) and lg D(L/B,7.4), respectively. An n-octano l/buffer system was also employed as the reference hydrophobicity, lg D(O/B,7.4)4. RESULTS: For the tested set, lg k(IAM) correlated more significantly with lg D(L/B,7.4) (r2 = 0.93) than with lgD(O/B,7.4) (r2 = 0.65). There were better correlations between either lg k(IAM) or lg D(L/B,7.4) and the extent of accumulation in AM than did lg DO/B,7.4 (r2 = 0.89, 0.92, and 0.67, respectively). Correlations obtained using lg k(IAM), lg D(L/B,7.4), and lg D(O/B,7.4) were comparable when regressed against the logarithm of influx rate into AM f or a set consisting of five amphoteric quinolones and quinidine. CONCLUSION: Liposome/buffer system and IAM chromatography could provide nearly similar scale of lipophilicity measurement, both distinct from n-octanol/buffer system. Accumulation by AM was better described by lg k(IAM) or lg D(L/B,7.4) than lg D(O/B,7.4), and the passive diffusion was principal form during drugs transported across AM membrane.

4-Quinolones↗