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Ya-Li Zhao

Publications and source records attributed to Ya-Li Zhao.

12 recordsLinked to original sources
PubMed2006

Synergistic effect of anionic lipid enhancer and electroosmosis for transcutaneous delivery of insulin.

A lipid formulation consisting of 1,2-dimyristoyl-sn3-phosphatidylserine (DMPS) in a 0.2% sodium dodecylsulfate (SDS) solution was tested as an in vivo enhancer for the transcutaneous delivery of insulin. The formulation when applied to for 15 min was found to permeabilize porcine epidermis and prolong the permeable state as evidenced by electric resistance measurement. The formulation enhanced the transport of insulin through the epidermis by 40- to 100-fold, as compared to epidermis that was treated with SDS or DMPS alone. Application of electroosmosis across the formulation-treated epidermis enhanced the transport of insulin by an additional 10-fold. Pharmacokinetic studies were carried out in Sprague-Dawley rats. Transcutaneous delivery of insulin with formulation treatment and electroosmosis increased the plasma level of insulin by approximately 10-fold over delivery by formulation treatment alone. With the above protocol plasma insulin concentration remained relatively constant for up to 4h. The synergistic application of anionic lipid formulation and electroosmosis offers a promising non-invasive technique to deliver insulin transcutaneously.

Administration, Cutaneous↗
PubMed2006

Lipid and electroosmosis enhanced transdermal delivery of insulin by electroporation.

Transdermal transport of insulin and extraction of interstitial glucose under anodal iontophoresis (electroosmosis) following electroporation in the presence of 1,2-dimyristoylphophatidylserine (DMPS) was studied. An earlier study showed that DMPS increased the transport of insulin across porcine epidermis under electroporation by approximately fourfold. It was suggested that DMPS increased the lifetime of electropores in the epidermis resulting in an enhanced transport of permeants. When electroosmosis was applied across the epidermis following electroporation with DMPS, the enhancement of insulin transport was approximately 18-fold over electroporation alone. When the same strategy was applied to extract interstitial glucose, the enhancement was approximately 23-fold over electroporation alone. Real-time transdermal insulin transport kinetics was measured using FITC-labeled insulin and a custom-made vertical diffusion apparatus that had a fluorescence cuvette as the receiver compartment. Insulin transport by electroporation alone showed a nonlinear kinetics that is most likely due to the resealing of the electropores with time. The transport kinetics when electroporation was carried out in the presence of DMPS was more linear, confirming earlier studies that suggested the DMPS stabilizes transport paths formed by electroporation. The data suggests that in vivo, noninvasive insulin delivery to therapeutic levels and glucose extraction may be achieved by combining electroporation with anionic lipids and electroosmosis.

Administration, Cutaneous↗
PubMed2006

A novel mutation of POU3F4 causes congenital profound sensorineural hearing loss in a large Chinese family.

OBJECTIVES/HYPOTHESIS: It is known that approximately 5% of congenital profound hearing impaired cases are inherited in X-linked inheritance. This study aimed at identifying its underlying molecular determinant(s) using a large, five-generation Chinese family with multiple familial cases. STUDY DESIGN: Model-based linkage analysis and positional cloning. METHODS: Model-based genetic linkage analyses were performed with the use of microsatellite polymorphisms to determine disease locus. Mutation screening was performed within the family and unrelated population-based controls to establish molecular evidence as to what caused the specific X-linked inheritance pattern in the family. RESULTS: Clinical investigations of the pedigree demonstrated the extremely high penetrance in the male members but no penetrance in the female members. Linkage analyses mapped the disease to the chromosomal region Xq13.I-Xq23 (maximum X-linkage logarithm of odds score = 3.27). Mutation screening of the candidate genes in the linkage region by direct sequencing revealed a de novo missense substitution (925T>C) in the well-known deaf gene. POU3F4. Direct sequencing on 240 unrelated controls did not detect any mutation. CONCLUSIONS: Multiple analysis approaches demonstrated that these disorders in the family were caused by a founder mutation in the POU3F4 gene. Our findings provided confirmatory molecular evidence to support that development of congenital profound sensorineural hearing loss in the Chinese population results from a novel mutation in the same gene.

Adolescent↗
PubMed2006

[Effect of diallyl disulfide on expression and secretion of VEGF in HL-60 leukemic cells].

The study was aimed to investigate the expression of VEGF mRNA and VEGF protein in HL-60 cells treated with diallyl disulfide (DADS), and to explore the antileukemic mechanism of DADS in respect of VEGF production. Semi-quantitative RT-PCR and ELISA were used to detect the expression of VEGF mRNA and secretion of VEGF protein in HL-60 cell lines treated by DADS respectively. The results showed that the expression of VEGF mRNA and secretion of VEGF protein were found in HL-60 cells. The expression of VEGF mRNA and secretion of VEGF protein in HL-60 cells could be down regulated by treatment with 0.625, 1.25, and 2.5 microg/mL DADS for 48 and 72 hours and the effects had a dose dependent relationship (r > 0.9, P < 0.01). The differences between DADS treated HL-60 cell groups and the control group were statistically significant (P < 0.01), there were also statistically significant differences among three DADS-treated HL-60 cell groups (P < 0.05). It is concluded that DADS effectively inhibits the proliferation of human leukemia cell line HL-60 cells; DADS exerts its antileukemic effects by reduction of the expression of VEGF mRNA and VEGF protein secretion.

Allyl Compounds↗
PubMed2006

[Expression and clinical significance of LRP16 gene in human breast cancer].

BACKGROUND & OBJECTIVE: Estrogen directly up-regulates LRP16 gene expression via activating its receptor (ER), and the overexpression of LRP16 promotes the proliferation of human breast cancer cells. This study was to detect the mRNA level of LRP16 gene in breast cancer, and investigate its correlation to the clinicopathologic features. METHODS: The mRNA level of LRP16 in carcinoma and matched peritumor tissues from 22 breast cancer patients was detected by Northern blot, and that in the tissues from 30 patients was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The expression of Ki-67, ER, and progesterone receptor (PR) in the carcinoma tissues was detected by immunohistochemistry. RESULTS: According to the results of Northern blot, compared with that in peritumor tissues, LRP16 was overexpressed by 2 folds in 9 (40.9%) out of 22 breast cancer samples. Of the 9 samples with LRP16 overexpression, 7 were ER-positive, and 8 were PR-positive; of the 13 samples without LRP16 overexpression, 6 were ER-positive, and 5 were PR-negative. The positive rates of ER and PR were significantly higher in the samples with LRP16 overexpression than in the samples without LRP16 overexpression (P<0.05). Only 1 of the 9 samples with LRP16 overexpression was negative for both ER and PR, but 7 of the 13 without LRP16 overexpression were negative for both of them. The proportion of the tumors with diameters of 3.0-4.5 cm was significantly higher in the patients with LRP16 overexpression than in those without LRP16 overexpression (8/9 vs. 5/13, P=0.031). Axillary lymph node metastasis was detected in 12 out of 22 patients, including 8 of the 9 patients with LRP16 overexpression and 4 of the 13 without LRP16 overexpression (P=0.011). In addition, LRP16 overexpression was detected in 6 of the 8 patients with Ki-67 overexpression, and 2 of the 14 patients without Ki-67 overexpression (P=0.026). According to the results of RT-PCR, LRP16 was overexpressed in 9 (30%) out of 30 breast cancer samples. All of the 9 samples with LRP16 overexpression were positive for both ER and PR, with Ki-67 overexpression, tumor diameters of more than 3.5 cm and axillary lymph node metastasis. The differences between the patients with or without LRP16 overexpression were significant (P<0.05). CONCLUSION: LRP16 overexpression is closely correlated to the positive rates of ER and PR, Ki-67 level, tumor diameter, and axillary lymph node metastasis of breast cancer, and might be involved in the proliferation and metastasis of human breast cancer.

Adult↗
PubMed2005

Electroporation and transcutaneous extraction (ETE) for pharmacokinetic studies of drugs.

The therapeutic activity and toxicity of drugs often depends on the accumulation of drugs in the peripheral anatomical compartment rather than the central compartment. In the routine practice of therapeutic drug monitoring (TDM) and pharmacokinetic studies, drug concentration determined by intermittent blood sampling is used as a surrogate for calculating the drug concentration in the peripheral compartment tissues. Microdialysis, a relatively less invasive procedure, has been used for estimation of free drug levels in dermal, subcutaneous and muscle tissues. Transcutaneous extraction of drugs from the dermal tissue is a good noninvasive alternative to phlebotomy and microdialysis. This requires a technique, which can facilitate the extraction of significant and reproducible amounts of drugs from the dermal extracellular fluid (ECF) within a short sampling duration. In the present work, we assessed the feasibility of electroporation and transcutaneous extraction (ETE) method for determining the time course of drugs in dermal ECF, using salicylic acid (SA) as a test drug. Electroporation protocol was optimized based on the in vitro diffusion studies of salicylic acid across rat skin. The concentration-time profile of total SA was determined in rats after a single i.v. bolus administration. The in vivo permeability coefficient (P(in vivo)) of rat skin was determined under steady state plasma concentration of drug created by i.v. bolus followed by constant rate infusion of SA. The pharmacokinetic parameters of the drug were determined using a two-compartment pharmacokinetic model. The theoretical predicted time course of free SA in the dermal ECF after a single i.v. bolus administration was calculated using standard formulae. The concentration of free SA determined by ETE is in good agreement with that calculated using two-compartment pharmacokinetic model. This study thus provides a credible evidence for the validity of ETE technique for determining the concentration of SA in the dermal ECF.

Animals↗
PubMed2004

Cyclodextrin enhanced transdermal delivery of piroxicam and carboxyfluorescein by electroporation.

The transdermal transport of cyclodextrins (CD) across porcine epidermis by electroporation was studied. Electroporation increased the permeation of beta-cyclodextrin (BCD) and hydroxy propyl beta-cyclodextrin (HPCD) by several orders of magnitude, relative to passive transport. The presence of BCD and HPCD enhanced the total transport of the test permeants piroxicam and carboxyfluorescein (CF), respectively, from both permeant solutions and suspensions. BCD enhanced the fraction of piroxicam transported across the epidermis into the receiver compartment medium. This was most likely due to the prolonged post-pulse permeability state of the epidermis. The fraction of CF retained in the epidermis was increased by HPCD. The rate of diffusion of CF from epidermis into the receiver compartment was decreased by the presence of HPCD, apparently due to the aggregate forming tendency of HPCD. The in vivo delivery of CF by electroporation in mice demonstrated the potential of HPCD for sustaining the transdermal absorption rate of hydrophilic molecules.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2004

Temperature influences the postelectroporation permeability state of the skin.

The influence of temperature on the electrical conductance and transport of macromolecules across porcine epidermis during and after electroporation were studied. The passive diffusion of fluorescein isothiocyanate labeled dextran (molecular weight 10 kDa, FD10K), across the epidermis did not differ much at temperatures below 37 degrees C, but became significantly higher above 40 degrees C. The resistance drop during pulse application was less sensitive to temperature within the temperature range (10-50 degrees C) of this study. The kinetics of decrease in postpulse conductance of the electroporated epidermis was fit to a monoexponential function. The rate of decrease in postpulse conductance was significantly less and FD10K transport was markedly high at temperature over 40 degrees C relative to those observed at temperatures less than 37 degrees C. This jump in transport cannot be explained by electrophoresis induced by the pulse, or by the increased diffusion kinesis of the molecules. The enhanced transport is most likely due to the prolonged postpulse permeable state of the skin. Electroporation at mild hyperthermia temperatures resulted in delivering much higher quantities of macromolecules.

Algorithms↗
PubMed2003

pH influences the postpulse permeability state of skin after electroporation.

The pH dependence of porcine epidermis permeability and the influence of pH on the electroporation transport of molecules were studied. The resistance was maximum at pH 5 and decreased with an increase or decrease in the pH of the donor medium. The permeability coefficient of glucose was significantly higher at pH 7.5, compared to pH 5. On electroporation, the resistance recovery rate of porcine epidermis was rapid below pH 5 and slower at above pH 7.5. The transport studies revealed that a donor medium pH above 7.5 helps to maintain the postpulse permeability state of the skin. By changing the donor medium pH from 5 to 7.5, the postpulse transport of glucose and fluorescein isothiocyanate (FITC)-labeled dextran (MW 10 kDa) (FD10K) was enhanced by about threefold. The lipids extracted from porcine epidermis showed pI values of 4.3 and 5.9. Vesicles of these lipids fused more rapidly at pH 5 than at pH 3, 7, and 10. The results imply that pH-sensitive postpulse resistance recovery and molecular transport are due to the charge states of epidermal lipids.

Animals↗
PubMed2003

[Inhibitory effect of antisense human telomerase reverse transcriptase(hTERT) on telomerase activity of human pulmonary giant cell carcinoma cell line(PLA-801D)].

BACKGROUND & OBJECTIVE: Telomerase has been thought to play an important role in the carcinogenesis in recent years. Human telomerase reverse transcriptase (hTERT) is a limiting component for telomerase activity. This study was designed to explore the effect of transfection of the full-length cDNA of antisense hTERT on the malignant phenotype of human pulmonary giant cell carcinoma cell line (PLA-801D) and its potential role in the gene therapy for cancers. METHODS: An antisense hTERT cDNA eukaryotic expression vector pcDNA3.1(-)-hTERT including the full length of hTERT cDNA sequence was constructed using recombinant DNA technique and transfected into human pulmonary giant cell carcinoma cells (PLA-801D) with liposome. The effect of antisense hTERT on the cellular proliferation capacity of PLA-801D cells was analyzed by the growth curve. The expression of hTERT mRNA was examined by reverse transcription polymerase chain reaction (RT-PCR). The telomerase activity was determined by telomeric-repeat amplification protocol enzyme-linked immunoassay (TRAP-ELISA). RESULTS: Antisense pcDNA3.1 (-)-hTERT eukaryotic expression have been constructed and was successfully transfected into the PLA-801D cells. The growth speed of PLA-801D transfected with antisense hTERT was significantly inhibited compared with the control cells, and the hTERT mRNA expression was inhibited, the relatively expression was only 15.7% of control cells, and telomerase activity was down-regulated about 82.4%. CONCLUSION: Full-length antisense hTERT cDNA can suppress hTERT mRNA expression and telomerase activity, and restrict the growth speed of tumor cells.

Carcinoma, Giant Cell↗
PubMed2002

Saturated anionic phospholipids enhance transdermal transport by electroporation.

Anionic phospholipids, but not cationic or neutral phospholipids, were found to enhance the transdermal transport of molecules by electroporation. When added as liposomes to the milieus of water-soluble molecules to be delivered through the epidermis of porcine skin by electroporation, these phospholipids enhance, by one to two orders of magnitude, the transdermal flux. Encapsulation of molecules in liposomes is not necessary. Dimyristoylphosphatidylserine (DMPS), phosphatidylserine from bovine brain (brain-PS), dioleoylphosphatidylserine (DOPS), and dioleoylphosphatidylglycerol (DOPG) were used to test factors affecting the potency of anionic lipid transport enhancers. DMPS with saturated acyl chains was found to be a much more potent transport enhancer than those with unsaturated acyl chains (DOPS and DOPG). There was no headgroup preference. Saturated DMPS was also more effective in delaying resistance recovery after pulsing, and with a greater affinity in the epidermis after pulsing. Using fluorescent carboxyl fluorescein and fluorescein isothiocyanate (FITC)-labeled Dextrans as test water-soluble molecules for transport, and rhodamine-labeled phospholipids to track anionic phospholipids, we found, by conventional and confocal fluorescence microscopy, that transport of water-soluble molecules was localized in local transport spots or regions (LTRs) created by the electroporation pulses. Anionic phospholipids, especially DMPS, were located at the center of the LTRs and spanned the entire thickness of the stratum corneum (SC). The degree of saturation of anionic phospholipids made no difference in the densities of LTRs created. We deduce that, after being driven into the epidermis by negative electric pulses, saturated anionic phospholipids mix and are retained better by the SC lipids. Anionic lipids prefer loose layers or vesicular rather than multilamellar forms, thereby prolonging the structural recovery of SC lipids to the native multilamellar form. In the presence of 1 mg/ml DMPS in the transport milieu, the flux of FITC-Dextran-4k was enhanced by 80-fold and reached 175 microg/cm(2)/min. Thus, the use of proper lipid enhancers greatly extends the upper size limit of transportable chemicals. Understanding the mechanism of lipid enhancers enables one to rationally design better enhancers for transdermal drug and vaccine delivery by electroporation.

Animals↗