Biomedical subjects

Jinming Gao

Publications and source records attributed to Jinming Gao.

29 records · Page 2Linked to original sources

PubMed2003

Noninvasive monitoring of local drug release using X-ray computed tomography: optimization and in vitro/in vivo validation.

In vivo release profiles of drug-loaded biodegradable implants were noninvasively monitored and characterized using X-ray computed tomography (CT). The imaging method was adapted and optimized to quantitatively examine the release of an active agent from a model cylindrical PLGA device (the millirod) into rabbit livers over 48 h. Iohexol, a CT contrast agent, served as a model drug; optimization of CT acquisition parameters yielded a sensitivity of 0.21 mg/mL (or 95 microg iodine/mL) for this agent. In vitro validation of the method was carried out by tracking release of iohexol in gelatin gel phantoms. In vivo release in rabbit livers was characterized through quantitative analysis of CT images and compared with UV-Vis analysis of the explanted devices at three implantation times. After correction for respiratory motion, CT analysis correlates well with the extracted iohexol data at all time points. The percent error between the actual and experimental image data was below 10%. This study demonstrates the potential of using computed tomography to noninvasively quantify the rate of agent release from controlled delivery devices in vivo.

Animals↗

PubMed2003

Enhancement of solubility and bioavailability of beta-lapachone using cyclodextrin inclusion complexes.

PURPOSE: To explore the use of cyclodextrins (CD) to form inclusion complexes with beta-lapachone (beta-lap) to overcome solubility and bioavailability problems previously noted with this drug. METHODS: Inclusion complexes between beta-lap and four cyclodextrins (alpha-, beta-, gamma-, and HPbeta-CD) in aqueous solution were investigated by phase solubility studies, fluorescence, and 1H-NMR spectroscopy. Biologic activity and bioavailability of beta-lap inclusion complexes were investigated by in vitro cytotoxicity studies with MCF-7 cells and by in vivo lethality studies with C57Blk/6 mice (18-20 g). RESULTS: Phase solubility studies showed that beta-lap solubility increased in a linear fashion as a function of alpha-, beta-, or HPbeta-CD concentrations but not gamma-CD. Maximum solubility of beta-lap was achieved at 16.0 mg/ml or 66.0 mM with HPbeta-CD. Fluorescence and 1H-NMR spectroscopy proved the formation of 1:1 inclusion complexes between beta-CD and HPbeta-CD with beta-lap. Cytotoxicity assays with MCF-7 cells showed similar biologic activities of beta-lap in beta-CD or HPbeta-CD inclusion complexes (TD50 = 2.1 microM). Animal studies in mice showed that the LD50 value of beta-lap in an HPbeta-CD inclusion complex is between 50 and 60 mg/kg. CONCLUSIONS: Complexation of beta-lap with HPbeta-CD offers a major improvement in drug solubility and bioavailability.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2003

Association between HLA-DQA1, -DQB1 gene polymorphisms and susceptibility to asthma in northern Chinese subjects.

OBJECTIVE: Human leukocyte antigen (HLA) class II genes, especially HLA-DQ genes, which are highly polymorphic, have been thought to be candidate loci for the etiology of asthma, and shown to be involved in antigenic presentation. This study was conducted to investigate whether susceptibility or resistance to asthma is associated with HLA-DQA1 and DQB1 genes polymorphism. METHODS: Venous blood samples were collected from northern Chinese population with Han ethnic. (1) One hundred and twenty-five unrelated asthmatic individuals and 52 subjects from 12 asthmatic pedigrees. (2) Ninety-six healthy controls without asthma and atopy with the same ethnic. Genomic DNA was extracted using standard phenol-chloroform method. The second exon of HLA-DQA1 and DQB1 genes were amplified by sequence-specific primer-polymerase chain reaction (SSP-PCR) method. All asthmatics had their serum IgE (total and specific) antibody or skin-prick test measured, bronchial reactivity to methacholine (Mch) and bronchial reversibility by beta(2)-agonist evaluated. RESULTS: HLA-DQA1 * 0104 allele and HLA-DQB1 * 0201 allele were significantly higher in asthmatics than those in healthy controls (0.408 vs 0.177, P < 0.01; 0.568 vs 0.198, P < 0.01). Odds ratios (ORs) were 3.203 (95% CI 1.699 - 6.037), 5.328 (95% CI 2.883 - 9.849) respectively. Conversely, HLA-DQA1 * 0301 allele and HLA-DQB1 * 0301 were significantly decreased in asthmatics compared to healthy controls (0.296 vs 0.50, P < 0.01; 0.4 vs 0.563, P < 0.05); Logistic regression analysis showed that HLA-DQA1 * 0104 allele was associated independently with asthma etiology, OR [represented by Exp(B)] was 5.0942 with 95% CI 2.2520 - 21.1813; Spearman's analysis showed that HLA-DQA1 * 0104 allele and HLA-DQB1 * 0201 allele were positively associated with atopy, the correlation coefficient were 0.183 and 0.289 respectively, P < 0.01. By contrast, HLA-DQA1 * 0301 allele was negatively related to atopy, the correlation coefficient was -0.168, P < 0.05; linkage analysis did not support the view that HLA-DQA1/DQB1 genes were linked to asthma with LOD value being 0.72. CONCLUSIONS: HLA-DQA1 * 0104 allele and HLA-DQB1 * 0201 allele were implicated in susceptibility to asthma and atopy, HLA-DQA1 * 0301 allele and HLA-DQB1 * 0301 might be protective factor against asthma. Asthma and atopy are multifactorial disorders, HLA-DQA1 and DQB1 genes are involved in the regulation of immune specific response to common allergen.

Adult↗

PubMed2002

Noninvasive monitoring of local drug release in a rabbit radiofrequency (RF) ablation model using X-ray computed tomography.

In this study, X-ray computed tomography (CT) was utilized as a noninvasive method to directly examine local drug release kinetics in livers before and following radiofrequency thermal ablation. Iohexol, a CT contrast agent, was used as a drug-mimicking molecule. Release of iohexol in healthy and ablated rabbit livers over 48 h was quantified and correlated with the release profiles from phosphate-buffered saline (PBS) in vitro. The results show that iohexol release in ablated livers is significantly slower than both release in normal livers and in vitro. The time at which 50% of the drug was released (t(1/2)) into ablated liver (20.6+/-5.9 h) was 1.7 times longer than in normal liver (12.1+/-5.4 h) and approximately two times longer than that in PBS (10.1+/-1.2 h). The slower release in ablated livers is a result of severe tissue damage inflicted by thermal ablation, as supported by histological examination. This data suggests that a noninvasive imaging method provides a superior measurement over in vitro release studies in accurately quantifying the local release kinetics of an agent in an altered physiological system in vivo. Because the development of a successful local drug therapy is dependent on the understanding of the agent release kinetics at the implantation site, the noninvasive data may be indispensable in effectively predicting the implant behavior in a physiological system.

Animals↗

PubMed2002

Combined modeling and experimental approach for the development of dual-release polymer millirods.

This paper describes a combined modeling and experimental approach for the design and development of a polymer device to provide local drug therapy to thermally ablated solid tumors. The polymer device, in the shape of cylindrical millirod, will be implanted via image-guided procedures into the center of the ablated tumor. Drug released from the millirod aims to eliminate residual cancer cells at the boundary of the normal and ablated tissue following thermal ablation to provide an effective treatment of the total tumor volume. The design of the millirod release kinetics is based on a mathematical model of drug transport in the ablated tumor and the surrounding normal tissue. The optimal release kinetics consists of a dual-release process-a burst release followed by sustained release-to provide the most optimal drug pharmacokinetics at the ablation boundary. Model analysis leads to a quantitative correlation of burst dose and release rates to the ablation size and the drug concentration at the ablation boundary. A three-layer polymer millirod is produced by a dip-coating method, and in vitro study demonstrates the dual-release kinetics in which a burst release occurs within 2 h followed by a sustained release over 7 -10 days. Independent control of the burst and sustained release rates is achieved by varying the structural composition of the outer and middle layers of the millirods, respectively. Results from this study provide the rational basis and experimental feasibility of dual-release millirods for further efficacy studies in solid tumors.

Antineoplastic Agents↗

PubMed2002

[Relationship between HLA-DQA1, -DQB1 genes polymorphism and susceptilibity to bronchial asthma among Northern Hans].

OBJECTIVE: To investigate the relationship between human leukocyte antigen (HLA)- DQA1, -DQB1 genes polymorphism and susceptibility to bronchial asthma among the Hans in the northern China. METHOD: Sequence-specific primer polymerase chain reaction was used to gene frequencies of HLA-DQA1 and HLA-DQB1 genes among 125 unrelated asthmatics, 12 of which being probands of asthmatic pedigrees, and 96 healthy controls, all of Han nationality and living in Beijing or nearby areas for a long time. Radioimmunosorbent test was used to examine the serum IgE and TigE. The ventilatory function was test among the asthmatics. RESULTS: The frequencies of HLA-DQA1 0104 and HLA-DQB1 0201 were 0.204 and 0.284, significantly higher than those in the healthy controls (0.089 and 0.096 respectively, both P < 0.01). Conversely, the frequencies of HLA-DQA10301 and HLA DQB101301 in the asthmatics were 0.148 and 0.20, significantly lower than those in the controls (0.25 and 0.282 respectively, P < 0.01 and < 0.05). The correlation coefficients between HLA-DQA1 * 0104 and atopy, HLA-DQB1 * 0201 and atopy, and HLA-DQA1 * 0301 and atopy were 0.813 (P < 0.01), 0.289 (P < 0.01), and -0.168 (P < 0.05) respectively. Multi-variate logistic regression asthma. CONCLUSIONS: The alleles HLA-DQA1 * 0104 and HLA-DQB1 * 0201 are correlated with the susceptibility to asthma among Northern of Han nationality. HLA-DQA1 * 0104 is an independent risk factor of onset of asthma. The alleles HLA-DQA1 * 0301 and HLA-DQB10301 are correlated with resistance against asthma. HLA-DQ genes are involved in the regulation of human specific immune responses.

Adult↗

PubMed2002

Membrane-encased polymer millirods for sustained release of 5-fluorouracil.

This article describes the design and development of a novel membrane-encased polymer millirod for the sustained release of an anticancer drug, 5-fluorouracil (5-FU). The millirod consists of two functional compartments: (1) an inner 5-FU-loaded monolithic millirod as the drug depot, and (2) an outer NaCl-impregnated polymer membrane to control the release rate of 5-FU. The inner millirod is fabricated by a compression-heat molding procedure to permit the entrapment of 5-FU particles in the poly(D,L-lactide-co-glycolide) (PLGA) matrix. The drug loading density is controlled at 30 w/w% to achieve a burst release of 5-FU (>90% of the drug are released within 48 h) from the monolithic millirod. The NaCl-impregnated PLGA membrane is generated by solvent casting and is then wrapped over the monolithic millirod to produce the membrane-encased millirod. Scanning electron microscopy shows that dissolution of NaCl particles produces a semipermeable polymer membrane to provide a sustained release of 5-FU. The membrane thickness and the density of NaCl particles inside the membrane are useful parameters to control the release kinetics of 5-FU. Under the experimental conditions in this study, sustained release of 5-FU [rates between 0.1 and 0.4 mg/(day. cm of millirod)] is achieved for 2 to 5 weeks in phosphate-buffered saline (pH 7.4) at 37 degrees C. Results from this study demonstrate that membrane-encased polymer millirods provide controllable sustained release kinetics for applications in intratumoral drug delivery.

Antineoplastic Agents↗

PubMed2002

In vivo drug distribution dynamics in thermoablated and normal rabbit livers from biodegradable polymers.

Image-guided radiofrequency ablation combined with intratumoral drug delivery provides a novel and minimally invasive treatment of liver cancers. In this study, the in vivo transport properties of doxorubicin in thermoablated and nonablated rabbit livers were characterized and compared. Doxorubicin was released from polymer implants (millirods) to the ablated and nonablated liver tissue. At different time points, the 2D distribution profiles were quantitatively determined by a fluorescence imaging method. Analysis of the doxorubicin concentration at the ablation boundary showed that it reached a maximum of 49.8 microg/g at 24 h after implantation, which was higher than the reported cytotoxic concentration of doxorubicin (6.4 microg/g) for liver VX-2 cancer cells. This value dropped to 0.4 microg/g at 48 h after implantation due to the depletion of doxorubicin from the polymer millirod. Results also showed that the area of drug distribution was significantly larger in ablated tissue than nonablated tissue. The therapeutic penetration distance was found to be 5.2 mm in thermoablated livers, compared to 1.2 mm in nonablated livers at 24 h. This difference in drug transport properties is attributed to destruction of the vasculature network in the ablated tissue as supported by histological analysis. Consequently, drug washout by blood perfusion is hampered while drug diffusion becomes the dominant process of transport in the ablated tissue. Results from this study provide insightful information on the rational design and development of polymer millirods for intratumoral drug delivery applications.

Animals↗

PubMed2002

X-ray computed tomography methods for in vivo evaluation of local drug release systems.

Recent advances in drug delivery techniques have necessitated the development of tools for in vivo monitoring of drug distributions. Gamma emission imaging and magnetic resonance imaging suffer from problems of resolution and sensitivity, respectively. We propose that the combination of X-ray CT imaging and image analysis techniques provides an excellent method for the evaluation of the transport of platinum-containing drugs from a localized, controlled release source. We correlated local carboplatin concentration with CT intensity, producing a linear relationship with a sensitivity of 62.6 microg/mL per Hounsfield unit. As an example application, we evaluated the differences in drug transport properties between normal and ablated rabbit liver from implanted polymer millirods. The use of three-dimensional visualization provided a method of evaluating the placement of the drug delivery device in relation to the surrounding anatomy, and registration and reformatting allowed the accurate comparison of the sequence of temporal CT volumes acquired over a period of 24 h. Taking averages over radial lines extending away from the center of the implanted millirods and integrating over clinically appropriate regions, yielded information about drug release from the millirod and transport in biological tissues. Comparing implants in normal and ablated tissues, we found that ablation prior to millirod implantation greatly decreased the loss of drug from the immediate area, resulting in a higher average dose to the surrounding tissue. This work shows that X-ray CT imaging is a useful technique for the in vivo evaluation of the pharmacokinetics of platinated agents.

Animals↗

PubMed2002

[Primary pulmonary lymphoma: analysis of cases and review of the literature].

OBJECTIVE: To study the clinical characteristics, diagnosis and treatment of primary pulmonary lymphoma. METHODS: Six cases of primary pulmonary lymphoma diagnosed from 1989 to 2000 were retrospectively analyzed, and the literature was reviewed with regard to its clinical manifestations, X-ray features, bronchoscopic findings, diagnosis and treatment. RESULTS: Primary pulmonary lymphoma was a rare form of lymphoma. Its diagnosis was difficult because of the lack of specific characteristics. The most common symptoms were cough (4/6) and fever (2/6). X-ray features included solitary or multiple nodules and consolidation. Hilar or mediastinal lymphadenopathy might be absent in the early stage. Bronchoscopic examination revealed bronchial constriction, chronic mucosal inflammation or nearly normal bronchi. Definite diagnosis was made by pathologic and immunohistochemical examinations of the lung tissue obtained through surgical operation, pleuroscopy, or percutaneous needle lung biopsy. Treatment modalities included surgical resection, radiotherapy and chemotherapy. The prognosis was associated with the malignancy of lymphoma. CONCLUSIONS: The clinical manifestations of primary pulmonary lymphoma are nonspecific. Misdiagnosis is common. Appropriate invasive biopsy procedures are necessary for early diagnosis.

Adult↗

PubMed2002

[Epidemiological survey of the incidence of bronchial asthma in occupational populations in Beijing area].

OBJECTIVE: To investigate the correlation of asthma incidence with environmental pollution. METHODS: We performed stratified-cluster-disproportional-random-sampling survey in the occupational populations from 10 professional systems by using an uniform protocol, questionnaire and procedure in this multicenter study. Original data were processed and statistically analyzed with SPSS 8.0 for windows. Prevalence rates were compared by chi(2) test. RESULTS: A total of 50,558 people supposed to cover more than 200,000 staff and workers were sampled. Six hundred and thirty asthmatics were identified and the overall prevalence rate in Beijing area was 1.25%. The incidence of asthma in occupational populations from urban commercial and trade circles, common chemical plants, and a certain petrochemical works was 0.51%, 1.06% and 2.81% respectively. The morbidity of asthma in the latter two populations was significantly higher than that in peasants (0.43%) in the remote outskirts of Beijing city (P < 0.01). The relative risk (RR) of asthma incidence in occupational populations from the commercial and trade circles, common chemical plants, the petrochemical works and the students in elementary and middle schools was 1.88, 2.79, 5.19 and 3.05 respectively as compared to peasants, the differences being statistically significant. CONCLUSION: The results suggest that the difference in asthma incidence in occupational populations may be attributable to environmental pollution.

Adolescent↗