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Biomedical subjects

Lin Song

Publications and source records attributed to Lin Song.

25 records · Page 2Linked to original sources

Effect of environmental interventions to reduce exposure to asthma triggers in homes of low-income children in Seattle.

The effectiveness of community health workers (CHWs) assisting families in reducing exposure to indoor asthma triggers has not been studied. In all, 274 low-income asthmatic children were randomly assigned to high- or low-intensity groups. CHWs visited all homes to assess exposures, develop action plans and provide bedding encasements. The higher-intensity group also received cleaning equipment and five to nine visits over a year focusing on asthma trigger reduction. The asthma trigger composite score decreased from 1.56 to 1.19 (Delta=-0.37, 95% CI 0.13, 0.61) in the higher-intensity group and from 1.63 to 1.43 in the low-intensity group (Delta=-0.20, 95% CI 0.004, 0.4). The difference in this measure due to the intervention was significant at the P=0.096 level. The higher-intensity group also showed improvement during the intervention year in measurements of condensation, roaches, moisture, cleaning behavior, dust weight, dust mite antigen, and total antigens above a cut point, effects not demonstrated in the low-intensity group. CHWs are effective in reducing asthma trigger exposure in low-income children. Further research is needed to determine the effectiveness of specific interventions and structural improvements on asthma trigger exposure and health.

Air Pollution, Indoor↗

[Visualization and thin sectional anatomy of the laryngeal cartilages].

OBJECTIVE: To establish digitized visible model of the laryngeal cartilages of the visible human, providing morphological data for image diagnosis and laryngectomy. METHODS: Cross-sectional images of fresh tissues from the Chinese visible human data set were reviewed, and the laryngeal cartilages structures data were used, the data was on a section-by-section basis. Three-dimensional computer reconstructions of the laryngeal cartilages were generated from these data by surface rendering on a SGI workstation. RESULTS: The digital images from the visible human offer unique insights into the complex anatomy and ossification of the laryngeal cartilages, the quality of the computerized 3D-reconstructed images was distinct and perfect. CONCLUSIONS: The visible human data set can provide complete and accurate data The digitized model of the laryngeal cartilages offer unique insights into the laryngeal anatomy, could be used for resident education, rehearsal of an unfamiliar surgery and for developing a new surgical approach.

Adult↗

[Protective effect of exogenous bcl-2 on spinal cord motoneurons following sciatic nerve axotomy in the rat].

The aim of this study was to investigate the protective effect of exogenous bcl-2 on spinal cord motoneurons following sciatic nerve axotomy. After epineurium suturing, sense bcl-2 (Ad/s-bcl-2), antisense bcl-2 (Ad/as-bcl-2), or reporter gene lacZ (Ad/lacZ) recombinant adenovirus or NS was injected into the sciatic nerve 0.5 cm distant from the sutured point respectively in different groups. The rats were transcardially perfused with 4% paraformaldehyde on postoperative 48 h, 7 d, 15 d and 30 d respectively and the spinal cords of L4 to L6 were harvested. X-gal staining, bcl-2 in situ hybridization and immunohistochemical staining, TUNEL (terminal deoxynucleotidyl transferase mediated dUTP nick end labeling) staining and AChE (acetyl cholinesterase) histochemical staining were used. We observed that the exogenous lacZ gene was expressed in the spinal cord of Ad/lacZ group, and sense bcl-2 significantly decreased the number of apoptotic motoneurons and the decreasing degree of AChE activity of the motoneurons in the spinal cord induced by sciatic nerve axotomy and accelerate AChE activity recovery. However, antisense bcl-2 increased the number of apoptotic motoneurons and the decreasing degree of AChE activity of the motoneurons in the spinal cord induced by sciatic nerve axotomy and prolonged AChE activity recovery. These results demonstrate that exogenous bcl-2 may protect motor neurons from injury induced by peripheral nerve axotomy.

Adenoviridae↗

A versatile prodrug approach for liposomal core-loading of water-insoluble camptothecin anticancer drugs.

We describe a versatile prodrug strategy for loading the liposomal lumen with water-insoluble camptothecins. The procedure involves conversion of an active camptothecin analogue to a 20-OR omega-aminoalkanoanic ester prodrug in which R = CO[CH(2)](n)()NH(2) and n = 1-3. The basic amino group of the prodrug serves three roles. First, at pH ranges of 3-5, the amine enhances aqueous solubility. Second, it enhances responsiveness to a transmembrane ammonium sulfate gradient across the liposomal bilayer, thereby facilitating active loading of the agent into the liposomal aqueous core. Third, at a physiological pH of 7 or above (the pH to be encountered following drug release at the tumor site), the nucleophilicity of the amine manifests itself and cyclization to the C-21 carbonyl carbon occurs. This cyclization triggers a rapid and convenient nonenzymatic decomposition process that releases active camptothecin. Accordingly, this novel liposomal approach offers a potential system for tumor-targeting prodrugs of many water-insoluble camptothecins, including the highly lipophilic and clinically attractive analogues SN-38, 9-nitrocamptothecin and DB-67. The rate of formation of the active agent at the tumor site can be controlled through the selection of n (the length of the alkyl spacer group).

Antineoplastic Agents, Phytogenic↗

The Seattle-King County healthy homes project: implementation of a comprehensive approach to improving indoor environmental quality for low-income children with asthma.

Pediatric asthma is a growing public health issue, disproportionately affecting low-income people and people of color. Exposure to indoor asthma triggers plays an important role in the development and exacerbation of asthma. We describe the implementation of the Seattle-King County Healthy Homes Project, a randomized, controlled trial of an outreach/education intervention to improve asthma-related health status by reducing exposure to allergens and irritants in the home. We randomly assigned 274 low-income children with asthma ages 4-12 to either a high- or a low-intensity group. In the high-intensity group, community health workers called Community Home Environmental Specialists (CHES) conducted initial home environmental assessments, provided individualized action plans, and made additional visits over a 12-month period to provide education and social support, encouragement of participant actions, provision of materials to reduce exposures (including bedding encasements), assistance with roach and rodent eradication, and advocacy for improved housing conditions. Members of the low-intensity group received the initial assessment, home action plan, limited education during the assessment visit, and bedding encasements. We describe the recruitment and training of CHES and challenges they faced and explain the assessment and exposure reduction protocols addressing dust mites, mold, tobacco smoke, pets, cockroaches, rodents, dust, moisture, and toxic or hazardous chemicals. We also discuss the gap between the practices recommended in the literature and what is feasible in the home. We accomplished home interventions and participants found the project very useful. The project was limited in resolving structural housing quality issues that contributed to exposure to indoor triggers.

Air Pollution, Indoor↗

Effects of fenvalerate on progesterone production in cultured rat granulosa cells.

In this study, primary serum-free cultured rat granulosa cells (rGCs) were used as a cellular model to investigate the effects of fenvalerate on progesterone production. Various concentrations (0, 1, 5, 25, 125 and 625 microM) of fenvalerate were added to the cell cultures for 24 h. rGCs were stimulated by compounds such as follicle-stimulating hormone (FSH), 8-bromo-cAMP or 22(R)-hydroxycholesterol (22R-HC). Progesterone production and intracellular cAMP content were measured in control and treated groups. Expression of P450 side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory protein (StAR) were monitored by real-time PCR and Western blotting. Results showed that fenvalerate inhibited basal progesterone production in rGCs in the absence of stimulators. This inhibition was stronger in the presence of FSH and was not fully reversed by 8-bromo-cAMP or 22R-HC. The increase of cAMP content, stimulated by FSH, was inhibited by fenvalerate implicating that the intracellular cAMP-dependent signal pathway was involved. Fenvalerate reduced mRNA and protein expression of P450scc. These results suggested that multi-site inhibition of progesterone production by fenvalerate including a cAMP-dependent protein kinase pathway and reduction on P450scc gene expression and/or its enzymatic activity in rGCs.

Animals↗

Molecular dynamics simulations and experimental studies of binding and mobility of 7-tert-butyldimethylsilyl-10-hydroxycamptothecin and its 20(S)-4-aminobutyrate ester in DMPC membranes.

The enhanced permeability and retention of liposomes in solid tumors makes liposomal formulations attractive for the targeting of various antitumor agents. This study explores the binding, orientation, and dynamic properties of a potent topoisomerase I inhibitor, 7-tert-butyldimethylsilyl-10-hydroxycamptothecin (DB-67), and its 20(S)-4-aminobutyrate ester prodrug (DB-67-AB) in DMPC liposomes by molecular dynamics (MD) simulations and experimental studies. MD simulations of an all-atom and fully hydrated liquid-crystalline bilayer (2 x 36 DMPC lipids) containing single molecules of DB-67 and DB-67-AB were conducted for up to 50 ns. Membrane/water partition coefficients for DB-67 and DB-67-AB vs pH were determined by ultracentrifugation. Fluorescence spectra and/or steady-state anisotropies were measured in various solvents and in DMPC liposomes. Kinetics for the reversible DB-67 lactone ring-opening in the presence and absence of DMPC liposomes were determined by HPLC with fluorescence detection. During the entire simulation time both DB-67 and DB-67-AB were located on the bilayer membrane near the polar ester groups of DMPC. The average depth of penetration for DB-67 and DB-67-AB was similar (12.4-13.2 A) with the prodrug's protonated amino group strongly solvated by surface water and lipid phosphate groups. Binding and fluorescence experiments revealed only a modest reduction in the binding affinity upon attachment of the ionized 4-aminobutyrate group onto DB-67. The binding microenvironment polarity resembles that of a polar solvent such as EtOH and DMSO. Kinetics experiments confirmed that DB-67 lactone hydrolysis is inhibited in the presence of DMPC liposomes, consistent with the reduced exposure of its lactone ring to water, as observed in the simulations. Both bound DB-67 and bound DB-67-AB have nonrandom orientations and reduced mobility in the membrane, especially for diffusion normal to the bilayer surface, and rotational relaxation, both of which are > or =2 orders of magnitude slower than in bulk water. MD simulations correctly predicted the high binding affinities for DB-67-AB to DMPC bilayers, protection of bound DB-67 toward lactone hydrolysis, and the lack of a substantial reduction in binding for the 20(S)-4-aminobutyrate prodrug of DB-67.

Antineoplastic Agents↗