Biomedical subjects

Di Song

Publications and source records attributed to Di Song.

5 recordsLinked to original sources

PubMed2006

Explosive photodissociation of methane induced by ultrafast intense laser.

A new type of molecular fragmentation induced by femtosecond intense laser at the intensity of 2 x 10(14) W/cm2 is reported. For the parent molecule of methane, ethylene, n-butane, and 1-butene, fluorescence from H (n = 3-->2), CH (A 2Delta, B 2Sigma-, and C 2Sigma+-->X 2Pi), or C2 (d 3Pi g-->a 3Pi u) is observed in the spectrum. It shows that the fragmentation is a universal property of neutral molecule in the intense laser field. Unlike breaking only one or two chemical bonds in conventional UV photodissociation, the fragmentation caused by the intense laser undergoes vigorous changes, breaking most of the bonds in the molecule, like an explosion. The fragments are neutral species and cannot be produced through Coulomb explosion of multiply charged ion. The laser power dependence of CH (A-->X) emission of methane on a log-log scale has a slope of 10 +/- 1. The fragmentation is thus explained as multiple channel dissociation of the superexcited state of parent molecule, which is created by multiphoton excitation.

Journal Article↗

PubMed2003

Modified resolution factor for asymmetrical peaks in chromatographic separation.

The quality of separation is measured by resolution factor (R(s)) between adjacent peaks. The current United States Pharmacopeia (USP) method for R(s) calculation assumes symmetrical peak shapes. In practice, perfectly symmetrical peaks are rarely encountered. The goal of this study was to correct the inaccuracy due to peak asymmetry by using a new formula for R(s) calculation. Peak tailing factor was incorporated into the formula for the calculation of R(s) to correct for the peak asymmetry. The resulting modified formula was compared with USP formula using simulated peaks and actual peaks. Through mathematical derivation, the modified R(s) was expressed as: R=[2(t(2)+W(2)/2(1-1/TF(2))-t(1)-W(1)/2(1-1/TF(1)))]/W(1)+W(2) where t(1) and t(2) are the retention times of two peaks, W(1) and W(2) are peak widths at baseline, TF(1) and TF(2) are USP tailing factors. All parameters used in the formula are available from commercial data analysis software. Comparisons of modified R(s) to USP R(s) showed that the modified R(s) provided a more accurate measure of peak separation at the baseline level.

Chromatography, High Pressure Liquid↗

PubMed2003

"Blue heart": characterization of a mifepristone-dependent system for conditional gene expression in genetically modified animals.

A detailed characterization of a cardiac muscle-specific, ligand-regulated gene expression system was performed in transgenic mice using the inducing ligand mifepristone (MFP). Several lines of double transgenic mice were created that expressed a bacterial lacZ reporter gene in the heart, under the control of a MFP-activated transcription factor constitutively expressed in cardiac muscle. The transgenic mice, which were administered MFP at a dose of 1 micromol/l in the drinking water, responded to the ligand within 24 h. Induction of beta-galactosidase enzyme activity in the heart continued for up to 21 days and resulted in an average 17-fold increase in enzyme activity. The highest individual animal response measured was a 94-fold increase in enzyme activity. The EC(50) for MFP induction of beta-galactosidase activity in the heart was 0.7 micromol/l when MFP was administered in the drinking water. Pharmacokinetic analysis of MFP dosing in wild-type FVB/N mice showed that absorption was very rapid (T(max) 1-10 min), bioavailability was modest ( approximately 10%) and the t(1/2) of MFP in mouse plasma was determined to be approximately 5 h. Thus, the system functions effectively in transgenic mouse heart where induction of gene expression is sensitive and can be accomplished by a simple and broadly applicable drinking water protocol.

Animals↗

PubMed2003

Effect of dimethyl sulfoxide on bladder tissue penetration of intravesical paclitaxel.

Our laboratory has shown that the efficacy of bladder cancer intravesical therapy is in part limited by the poor penetration of drugs into the urothelium. We further found that paclitaxel, because of its lipophilicity, shows a higher penetration than other commonly used drugs such as mitomycin C and doxorubicin. However, the commercial formulation of paclitaxel (i.e., Taxol) contains Cremophor, which forms micelles that entrap the drug and reduce its free fraction. The present study evaluated the effect of DMSO on paclitaxel release from Cremophor micelles and paclitaxel penetration in bladders of dogs given an intravesical dose of paclitaxel (500 microg/20 ml in 0.22% Cremophor, 0.21% ethanol, and 50% DMSO). Cremophor produced a concentration-dependent reduction of the free fraction of paclitaxel (reduced to 23% at 0.25% Cremophor). This Cremophor effect was reversed by DMSO in a concentration-dependent manner, resulting in a 92% free fraction at 50% DMSO. DMSO also increased the average size of Cremophor micelles from 13 nm to 230 nm at 50% DMSO. A comparison of the tissue penetration data in the presence of Cremophor and/or DMSO indicates the following effects of DMSO: (a). increase in urine production rate and, consequently, a 36% reduction of the final urine concentration; (b). 2-fold increase in paclitaxel penetration across bladder urothelium; (c). increase in drug removal from bladder tissues (30% more rapidly); and (d). a 60% increase of the amount of drug in bladder tissue. These results indicate that DMSO caused rearrangement of Cremophor micelles, reversed the entrapment of paclitaxel in Cremophor micelles and thereby increased the free fraction of paclitaxel in solution, enhanced the urine production rate and enhanced drug removal by the perfusing capillaries, with an overall effect of increasing the bladder tissue delivery of paclitaxel formulated in Cremophor.

Animals↗

PubMedDate not supplied

Gel electrophoresis-autoradiographic image analysis of radiolabeled protein drug concentration in serum for pharmacokinetic studies.

INTRODUCTION: The purpose of this study was to evaluate the feasibility of using gel electrophoresis combined with autoradiographic image analysis for quantitating protein drug concentrations in biological fluid for pharmacokinetic studies. METHODS: Protein drugs were iodinated using the Iodogen reagent and injected into Sprague-Dawley rats for pharmacokinetic evaluation. Serum samples were analyzed using trichloroacetic acid (TCA)-precipitable counts or sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Commercially available precasted Bis-Tris gradient gels were used for SDS-PAGE. Autoradiography of gel samples was performed using phosphoimager and quantitated using the ImageQuant software. RESULTS: The maximum loading volume for protein drugs with molecular weight close to that of albumin ( approximately 70 kDa) was about 1 microl, whereas for protein drugs with larger or smaller molecular weight (i.e., >80 or <40 kDa), the maximum loading volume was up to 20 microl/lane. The optimal exposure time was about 18 h or overnight. Standard curves were constructed using serially diluted dosing solution, which was linear over a 10-fold concentration range with a correlation coefficient of.98. Comparing to the soluble human interleukin-13 receptor (shIL-13R) pharmacokinetic profiles from TCA-precipitable counts, the quantitative gel analysis revealed lower concentrations at later time points and a lower bioavailability from intraperitoneal injection. DISCUSSION: This study provided the first systemic evaluation of gel electrophoresis technology for quantitative protein drug determination in serum and its application in pharmacokinetic studies. The combination of gel electrophoresis with autoradiographic image analysis provided accurate and specific quantitation results. The overnight turnover time allowed routine application in preclinical pharmacokinetic studies.

Animals↗