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Biomedical subjects

J M Zheng

Publications and source records attributed to J M Zheng.

13 recordsLinked to original sources

Effect of electroporation and iontophoresis on skin permeation of Defibrase--a purified thrombin-like enzyme from the venom of Agkistrodon halys ussuriensis Emelianov.

The purpose of this study was to investigate electroporation and iontophoresis as a means for in vitro delivery of Defibrase--a thrombin-like enzyme (TLE) from Agkistrodon halys ussuriensis Emelianov snake venom--through human epidermis membrane (HEM). Electroporation was carried out using an exponential decay pulse generator (BioR-ad Genepulser, USA) for a period of 0.5 h, followed by a period of 5.5 h passive diffusion or iontophoresis. The results indicated that the combined use of electroporation and anodal iontophoresis in pH 6.4 permeation medium could effectively enhance the skin permeation of Defibrase, whose apparent permeability coefficient was 1.6 +/- 0.8 x 10(-4) cm.h-1. The delivery of Defibrase by the combined use of electroporation and anodal iontophoresis was more effective than by electroporation alone (P < 0.01) or by the combined use of electroporation and cathodal iontophoresis (P < 0.01). Moreover, when the pH of the permeation medium was raised from 6.4 to 7.4 the permeation of Defibrase caused by a combined use of electroporation and anodal iontophoresis showed a tendency to increase. These results implied that electroosmotic flow effect might be important for the iontophoretic (following electroporation) skin permeation of Defibrase.

Batroxobin↗

Variation of ER status between primary and metastatic breast cancer and relationship to p53 expression*.

OBJECTIVE: Estrogen-dependent growth of breast cancer can be blocked by anti-estrogens. Estrogen receptor (ER) presence in breast cancer implies responsiveness to endocrine therapy. However, for those patients who ultimately develop resistance to endocrine therapy, the mechanisms remain unclear. The present study attempted to compare the expression status of ER mRNA in a series of primary breast tumors with matched metastases and explored the relation between ER and mutant p53 expression. METHODS: In situ hybridization using a digoxigenin-labeled estrogen receptor cDNA probe was employed to determine the expression of ER mRNA in 52 cases of primary tumors and their matched axillary lymph node metastases. Immunohistochemical staining using a monoclonal antibody against ER was also performed. RESULTS: ER expression was observed in 53.8% (28/52) of primary tumors and 48% (25/52) of metastases, while 57.7% (30/52) of primary tumors and 53.8% (28/52) of metastases showed ER mRNA positivity. There were variations in ER status between in situ hybridization and immunohistochemistry measurements and between primary tumors and metastases. Mutant p53 expression was inversely associated with ER-negative, high-grade tumors. CONCLUSIONS: In situ hybridization may be a more specific and sensitive method for determination of ER status than immunohistochemistry. It is possible that the biologic properties of ER change, and these changes may influence tumor response to endocrine therapy. In view of the ER variation, it was suggested that the ER status of metastatic tumors in addition to primary tumors should be taken into consideration in order to better determine the benefit of clinical endocrine therapy.

Breast Neoplasms↗

[Construction of a Flp "exchange cassette" contained vector and gene targeting in mouse ES cell].

Using the HPRT genomic DNA fragment and synthesized oligonucliotides, pSP-HPRT-F-Neo-F3 was designed and constructed as a replacement gene targeting vector by usual molecular cloning techniques. Structure of pSP-HPRT-F-Neo-F3 was identified by restrictive digestion analysis and partly sequencing. Then linearized pSP-HPRT-F-Neo-F3 DNA was electroporated into ES cells, and transfected cells were screened by being cultured in medium containing 200 micrograms/mL G418 and 2 micrograms/mL 6-GT. Twenty-four double drug resistant clones were picked up and analyzed, among them, two clones were proved to have taken place the required recombination by PCR and southern blotting analysis.

Animals↗

[The study of a HPRT locus-specific transgenic method based on FLP recombinase mediated cassette exchange].

Exchange plasmid pF-HPRT-F3 and Flp expression plasmid pCMV-Flp were constructed and then introduced using electroporation system into F18 ES cell line, which have an exchange cassette F-Neo-F3 at HPRT locus. After HAT selection, HAT resistant clones were obtained. Then G418 sensitivity test and Southern blotting were carried out to screen RMCE recombinants. The results indicated that RMCE had taken place in three of 12 HAT resistant clones. The frequency is 25%. The result demonstrates that it is realizable to introduce transgene to HPRT locus by using Flp recombinase mediated cassette exchange reaction.

Animals↗

[Effect of pH on the permeability of timolol maleate across isolated rabbit cornea].

AIM: To study the effect of pH on the transcorneal permeability of timolol maleate (TM). METHODS: The apparent distribution coefficients of TM were determined. The permeability of TM across isolated rabbit cornea was measured using in vitro method at various pH. RESULTS: The partition coefficient and pKa of TM were 63.63 and 9.17 respectively. At neutral pH, the apparent permeation coefficient of TM was 1.43 x 10(-5) cm.s-1. When the pH varied from 6.65 to 9.20, the cumulative amount for timolol transcorneal penetration increased 1.3 times and the lag time decreased more than 19-folds. The calculated permeability coefficients of ionized and un-ionized timolol were 1.29 x 10(-5) cm.s-1 and 4.22 x 10(-5) cm.s-1, respectively. CONCLUSION: Timolol penetrated corneal membrane mainly as free base by intracellular pathway, and corneal epithelium was the rate-limiting barrier.

Animals↗

Crystallization and preliminary X-ray analysis of the thermostable sweet protein mabinlin II.

Mabinlin II is a sweet protein with the highest known thermostablility and is isolated from the seeds of Capparis masaikai Levl. grown in south China. Two crystal forms of mabinlin II were obtained using the hanging-drop vapour-diffusion method. One of them diffracts to 2.8 A resolution and belongs to space group P2, with unit-cell parameters a = 50.16, b = 50.17, c = 76.60 A, beta = 99.6 degrees. There are four molecules per asymmetric unit, with a solvent content of 35.3%.

Crystallization↗

[ Studies on some physical characteristics of cyclosporine A (CyA) solid dispersions].

In this paper, poloxamer and PVP were used as carriers. CyA-poloxamer and CyA-PVP solid dispersions were prepared using the melting-solvent method or solvent method, respectively. The percentage compositions of the solid dispersions ranged from 10:90 to 90:10. Hot stage microscopy, powder X-ray diffraction and differential scanning calorimetry were used to examine the physical-chemical characteristics of the solid dispersions to provide some reliable and scientific basis for preformulation of CyA.

Calorimetry, Differential Scanning↗

[Transdermal iontophoresis of insulin: effect of penetration enhancers on blood glucose level in diabetic rats].

The effects of many usual penetration enhancers such as azone (AZ), oleic acid (OA), poloxamer 188 (POL 188) and propylene glycol (PG) on the blood glucose level in diabetic rats after transdermal iontophoresis of insulin were studied. The change of blood glucose level (D%), defined as the percent ratio of the concentration of blood glucose in rats after the iontophoretic application of insulin to that before administration of insulin, was used to present the data. The results showed that following iontophoretic application of insulin for 3 h, the D% in diabetic rats treated with 100% AZ and 5% AZ/PG was 38.58% and 25.28% respectively, and the D% in diabetic rats untreated with enhancers was 45.48%. The D% in diabetic rats treated with 100% OA, 10%-OA/PG, 10% POL 188/PG and 100% PG was 66.28%, 60.47%, 76.75% and 57.93% respectively. So, AZ showed a synergistic effect on the ability of iontophoresis to promote skin permeation of insulin, and PG further increased this effect. The combination of AZ, PG and iontophoresis increased the permeation of insulin significantly. OA, POL 188 and PG did not display synergistic effect on iontophoresis enhancement. The combination of iontophoresis and some enhancers provided a novel idea and possibility for the administration of polypeptide drugs.

Administration, Cutaneous↗

[Research on nifedipine patch].

The feasibility of matrix dispersion-type nifedipine patch was verified and an HPLC method for the determination of nifedipine level both in vitro and in vivo was established. It was found that both the two formulations of the patch (R2 with azone as penetration enhancer, R1 without azone) provided zero order kinetics of permeation, the rates of skin permeation were different at less than 10.25 and greater than 10.25 h, R1 was 2.63 and 1.1 micrograms/cm2. h; R2 was 4.30 and 1.54 micrograms/cm2.h. The release profiles of nifedipine from R2 were found to follow a linear Q vs t1/2 relationship with a release flux of 68.91 micrograms/cm2. h1/2. The plasma concentration vs time profiles of nifedipine in healthy subjects, each receiving two patches (36 x 2 cm2), were investigated. A steady state plasma level within therapeutic concentration window was obtained from 1.5 h to 24.5 h. Several quality tests of the patch were evaluated in this research.

Administration, Cutaneous↗

[Use of derivative UV spectroscopy to monitor the percutaneous absorption of befunolol-HCL].

Second-order derivative UV spectroscopy was used to measure the transfer of befunolol-HCl across full-thickness rabbit skin in vitro. The effect of penetration enhancers, azone-PG and PEG-400, on permeation course of befunolol-HCl was studied. A type of horizontal diffusion cell was employed. Permeability coefficients were measured in normal saline and in solutions containing the enhancing agents. The results indicated that befunolol-HCl may be an interesting candidate for transdermal administration and azone-PG highly and significantly increases the skin permeation of the drug in the solvent system tested.

Administration, Cutaneous↗