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Biomedical subjects

Y B Huang

Publications and source records attributed to Y B Huang.

At least 19 recordsLinked to original sources

Organogenesis of pancreatic anlagen allografted in rats.

AIMS: To study the possibility of revascularization, growth, and differentiation of embryonic pancreatic anlagen transplanted to adult hosts. While transplantations of pancreas and islets are the main methods to cure diabetes mellitus, the donor source is in shortage. So it's necessary to find a new source for transplantation. METHODS: The pancreas from embryonic day 14.5 (E14.5) and 15.5 (E15.5) Lewis rat embryos were implanted into either intraperitoneal or subrenal capsular site of healthy Lewis rats. at 3 weeks or 6 weeks after implantation, the pancreatic anlagen in the host rats were resected for size measurements, as well as histopathologic and immunohistochemical examinations. RESULTS: Three weeks after implantation into the renal-capsular site, the size of both E14.5 and E15.5 pancreatic anlagen had enlarged 10- to 15-fold with differentiation of acinar components upon histological examination. Moreover, increasing numbers of beta cells and islets stained positive for insulin, and newly generated vessels were observed around the tissues. Continued proliferation of the endocrine islets in E14.5 pancreatic anlagen grafts was observed after another 3 weeks, whereas further proliferation in the E15.5 pancreatic anlagen graft was not seen. Additionally fibrosis appeared in the exocrine component of both E14.5 and E15.5 pancreatic anlagen at this time point. When implanted into intraperitoneal site, enlarged E15.5 pancreatic anlagen with proliferatels beta cells were also observed after 3 weeks. However, both the size of the pancreatic anlagen and the proliferation of the beta cells were much less than that in the subrenal capsular site. CONCLUSIONS: The allografted E14.5 and E15.5 pancreatic anlagen revascularised and grew into tissues that were structurally similar to normal mature rats pancreatic tissue. Adequate embryonic age for the transplantation of pancreatic anlagen is 14.5 and 15.5 days old. Subrenal capsula is a more suitable site than the peritoneal cavity for implantation of pancreatic anlagen.

Animals↗

Sertoli cells induce xenolymphocyte apoptosis in vitro.

BACKGROUND: Testicular Sertoli cells can protect pancreatic islet grafts from allo- and autoimmune destruction; however, the mechanisms underlying immune privilege of the testicle are not well understood, especially in xenotransplantation. The purpose of this study was to investigate whether rat Sertoli cells could induce mouse lymphocyte apoptosis in vitro. METHODS: Testis was isolated from 2- to 4-week-old Sprague Dawley (SD) rats. Sertoli cells were successfully prepared by digestion with collagenase type V, trypsin, and DNase I, and then identified by electron microscope. Viability and apoptosis of cultured cells were measured by flow cytometry. We examined the apoptosis rates of Balb/c mouse lymphocytes, which were cocultured with SD rat Sertoli cells by FACS. The expression of Fas ligand (Fasl), transforming growth factor (TGF)-beta1 and clusterin on Sertoli cells were detected by immunocytochemistry. RESULTS: In the cocultured system, Sertoli cells accounted for more than 93%. With our isolation method, the viability of Sertoli cells was more than 95% and the apoptosis rate was 10.87% +/- 3.87%. The lymphocyte apoptosis ratio was 15.52 +/- 0.17 (P < .01, compared with the control groups). SABC immunochemistry staining showed that the sertoli cells could express FasL, TGF-beta, and clusterin. CONCLUSIONS: In our coculture in vitro, rat Sertoli cells expressed FasL and TGF-beta1 as well as induced the apoptosis of mouse lymphocytes. These results indicated that the expression of FasL and TGF-beta1 on Sertoli cells might relate to immune privilege in xenotransplantation.

Animals↗

Induction of accommodation model by combined RNA interference targeting 1,3-galactosyltransferase gene and low-dose GS-IB4 lectin in vitro.

OBJECTIVE: This study sought to mimic the interaction of xenograft endothelial cells and human serum in vitro after successfully silencing the expression of porcine alpha1,3-galactosyltransferase (alpha1,3GT) gene by RNA interference (RNAi), and to investigate the possibility of inducing accommodation in vitro by stimulation of alpha-Gal-specific binding lectin, Griffonia simplicifolia isolectin B4 (GS-IB4) and RNAi. MATERIALS AND METHODS: Various alpha-Gal expression patterns on a pig endothelial cell immortalized line (PED) was achieved by serial doses of small interfering RNA (siRNA) targeting porcinc alpha1,3GT gene. alpha1,3GT-siRNA transfected PEDs were exposed to increasing doses of GS-IB4 lectin (0.5, 2, and 8 microg/mL) for 4 hours before incubation with normal human serum (NHS). Accommodation phenomenon of PEDs in NHS was observed by 51Cr release and antibody/complement binding assays. RESULTS: With combined RNAi and low-dose GS-IB4 stimulation, PEDs remarkably inhibited complement-mediated cytotoxicity, which showed a better protective effect than using RNAi alone. At a concentration of 2 mug/mL, GS-IB4 exhibited the maximum protective effect. The expression of E-selectin on alpha1,3GT-siRNA transfected PEDs did not differ from that on parental PEDs with heat-inactivated NHS (HINHS) stimulation. Combined with GS-IB4 stimulation, however, it inhibited expression of E-selectin, which was GS-IB4 dose dependent, resulting in mean fluorescence intensity values of 98.5, 42.0, and 36.3 at 0.5, 2, and 8 microg/mL. The mRNA expression of the protective gene HO-1 was significantly up-regulated after treatment with RNAi and low-dose of GS-IB4. CONCLUSIONS: Combined RNAi and low-dose GS-IB4 induced pig endothelial cell accommodation in vitro. The level of alpha-Gal expression played an important role in the induction of accommodation.

Animals↗

Effects of the silanized mica surface on protein crystallization.

A freshly cleaved mica surface silanized by 3-aminopropyl triethoxysilane is flat over a large area, displays a controlled degree of hydrophobicity and contains positive charges. In this paper, mica sheets silanized by this method have been used as crystallization surfaces for lysozyme, trichosanthin and three other proteins of unknown structure. Crystallization experiments have been carried out by the hanging-drop vapour-diffusion technique and the results indicate that the silanized mica surface can ameliorate the protein crystallization process considerably compared with a silanized glass cover slip control. For lysozyme on the silanized mica surface, the induction time required for crystal growth decreases markedly. For trichosanthin, the crystal size is obviously larger and the number of crystals grown is much lower. For the three proteins of unknown structure, the diffraction ability of the crystals is improved considerably.

Aluminum Silicates↗

Evaluation of percutaneous absorption and skin irritation of ketoprofen through rat skin: in vitro and in vivo study.

The influences of different mechanisms of penetration enhancers (such as menthol, azone, ethanol and nonivarnide) regarding the percutaneous absorption and skin irritation of ketoprofen formulations through rat skin were investigated by in vitro and in vivo study. The skin irritation degree at the end of the experiment (10 h) was deterinined by pathologic biopsy and colorimetry methods. In vitro, the menthol showed the most potent enhancing effect. Furthermore, the enhancement effect of a combination of menthol and nonivamide was higher than that of their individual use alone. In vivo the formulation containing 0.05% nonivantide, 5% menthol and 20% ethanol showed a higher penetration rate and an acceptable degree of skin irritation compared to a commercial product (Formax plus gel containing 3% ketoprofen), indicating that it could be used in the clinical situation.

Animals↗

In vitro skin permeation of estradiol from various proniosome formulations.

The skin permeation of estradiol from various proniosome gel formulations across excised rat skin was investigated in vitro. The encapsulation efficiency and size of niosomal vesicles formed from proniosomes upon hydration were also characterized. The encapsulation (%) of proniosomes with Span surfactants showed a very high value of about 100%. Proniosomes with Span 40 and Span 60 increased the permeation of estradiol across skin. Both penetration enhancer effect of non-ionic surfactant and vesicle-skin interaction may contribute to the mechanisms for proniosomes to enhance estradiol permeation. Niosome suspension (diluted proniosomal formulations) and proniosome gel showed different behavior in modulating transdermal delivery of estradiol across skin. Presence or absence of cholesterol in the lipid bilayers of vesicles did not reveal difference in encapsulation and permeation of the associated estradiol. The types and contents of non-ionic surfactant in proniosomes are important factors affecting the efficiency of transdermal estradiol delivery.

Cellulose↗

Influence of electrical and chemical factors on transdermal iontophoretic delivery of three diclofenac salts.

The aim of this present study was to investigate the in vitro transdermal iontophoretic delivery of three diclofenac salts--diclofenac sodium (DFS), diclofenac potassium (DFP), and diclofenac diethylammonium (DFD). A series of physicochemical and electrical variables which might affect iontophoretic permeation of diclofenac salts was studied. Application of 0.3 mA/cm2 current density significantly increased the transdermal flux of diclofenac salts as compared to passive transport. The iontophoretic enhancement increased in the order of DFS>DFP>DFD. The permeability coefficient of diclofenac salts all decreased with increasing donor concentration during iontophoresis. The addition of buffer ions and salt ions such as NaCl, KCl, and C4H12ClN reduced the permeation of diclofenac salts due to competition. However, this effect was lesser for DFD than for DFS and DFP. Comparing the various application modes of iontophoresis, the discontinuous on/off mode showed lower but more constant flux than the continuous mode.

Administration, Cutaneous↗

Evaluation of pharmacokinetics and pharmacodynamics of captopril from transdermal hydrophilic gels in normotensive rabbits and spontaneously hypertensive rats.

The purpose of this investigation was to assess the pharmacokinetics (plasma concentration) and pharmacodynamics (heart rate, blood pressure (BP), and plasma renin activity (PRA)) of captopril experimental gel in normotensive rabbits and spontaneously hypertensive rats (SHRs) by reference to a short duration intravenous administration of the drug. In normotensive rabbits, the blood concentration versus time course of captopril after transdermal administration could be described well by a two-compartment model, and the maximum plasma concentration (5. 68+/-2.05 microg ml(-1)) was achieved in about 7 h. The increase in plasma captopril concentration led to increases in PRA and reductions in BP. A simple E(max) model adequately described the relationship between the percentage change of mean blood pressure (MBP) and the blood concentration of the captopril. The maximum reduction in MBP (E(max)) was 36.23% and the concentration at half maximum effect (EC(50)) was 0.24 microg ml(-1). The captopril was continuously released from the gel formulation and protected the SHRs in lower BP throughout the period of transdermal therapy. These results indicated that the development of captopril transdermal drug delivery system was possible. Further research was warranted on a modified formulation of captopril, which was optimized for transdermal delivery of the drug.

Administration, Cutaneous↗

Evaluation of transdermal iontophoresis of enoxacin from polymer formulations: in vitro skin permeation and in vivo microdialysis using Wistar rat as an animal model.

Polymers were used in vehicles to form hydrogel matrices in this study to evaluate the in vitro permeation and in vivo microdialysis of enoxacin. The highest transdermal delivery determined by area under flux-time curve (AUC) and intracutaneous enoxacin concentration were observed in methylcellulose (MC) and polyvinylpyrrolidone (PVP) hydrogels, respectively. To avoid the pH shift in vehicles during iontophoresis, buffer species were added to formulations to increase the buffer capacity. As expected, the permeability of enoxacin of anodal iontophoresis was larger than that of cathodal iontophoresis. Combination of benzalkonium chloride, a cationic surfactant as an enhancer, and iontophoresis exerted an enhancing effect for anionic enoxacin at pH 10.0. However, no effect or a negative effect was detected for cationic enoxacin in deionized water or pH 5.0 buffer, due to the shielding of the negative charge in the skin. The skin residue of enoxacin was slightly increased after the incorporation of Azone in PVP hydrogel. The result of in vivo microdialysis was in accordance with that of in vitro study. The effect of Azone on the intracutaneous enoxacin was more significant for in vivo microdialysis than in the in vitro study indicating the clinical feasibility of Azone for iontophoretic delivery. Microdialysis can be considered as a useful technique to investigate the pharmacokinetics of transdermal iontophoresis in vivo.

Administration, Cutaneous↗

Evaluation of topical application of clobetasol 17-propionate from various cream bases.

The effect of clobetasol 17-propionate (CP), a potent corticosteroid, in various cream bases on the permeation through artificial membrane was sought. Four formulations were then chosen for a further in vivo skin blanching assay. After calculation of the relationship between in vivo flux0-8 hr determined from a surface recovery technique and in vitro release rate0-8 hr of CP from various formulations, a high correlation coefficient of 0.9996 was achieved. Therefore, the in vitro release study could be used as an index to predict and evaluate the in vivo penetration capacity of CP cream to screen the effective formulation preclinically. After a series of in vivo investigations in this study, it was concluded that myristic acid-added formulations may show a bioequivalence with commercial Dermovate. Furthermore, the flux calculated from the surface recovery technique and delta E detected from the skin blanching assay may be useful as parameters evaluating the quality and effectiveness of CP cream.

Administration, Topical↗

In vitro study of transdermal nicotine delivery: influence of rate-controlling membranes and adhesives.

The objective of this study was to evaluate the influence of a rate-controlling membrane and adhesive on the in vitro permeation of nicotine. The physicochemical properties of the adhesive, including adhesion and rheology (viscosity), were also detected. Higher permeability of nicotine was observed through a hydrophilic membrane than through a hydrophobic membrane. Natural rubber and silicone were used as the adhesive bases, respectively. The silicone adhesive showed the highest adhesion among all adhesive formulations. To increase the adhesion of natural rubber, a tackifier (polyisoprene) and a secondary tackifier (terpene polymer; Px 1150) were incorporated into the formulations to achieve acceptable adhesion. The nicotine permeation through silicone adhesive and three natural rubber adhesives with the secondary tackifier (2%, 4%, and 6% Px 1150) was close to that from a commercially available patch (Habitrol), although the loading amount of nicotine was not the same. A longer lag time during the in vitro permeation study of nicotine was required for the adhesives prepared in our laboratory than for the commercially available patch.

Adhesives↗

Cyclic monoterpene extract from cardamom oil as a skin permeation enhancer for indomethacin: in vitro and in vivo studies.

The in vitro and in vivo effect of pretreatment by cardamom oil, a crude drug extract, in ethanol/water vehicles on the transdermal delivery of indomethacin was investigated. The cyclic monoterpene components in cardamom oil were also determined and quantified in this study. The permeation of indomethacin was significantly enhanced after pretreatment of cardamom oil both in the in vitro and in vivo studies. The result of various pre-treatment periods showed that the indomethacin flux decreased as the length of the pretreatment increased. Both natural cardamom oil and a cyclic monoterpene mixture composed of the components of the oil showed similar enhancement on indomethacin permeation, indicating cyclic monoterpenes are the predominant components altering the barrier property of stratum corneum. The results also showed that three minor components in cardamom oil (alpha-pinene, 6.5%; beta-pinene, 4.8%; alpha-terpineol, 0.4%) had a synergistic effect with 1,8-cineole (59.3%) and d-limonene (29.0%) to enhance the permeation of indomethacin.

Adult↗

Hyperlipidemia of normal pregnancy in Karachi-Pakistan.

During pregnancy, changes in the levels of total cholesterol, triglyceride, low density lipoprotein-cholesterol, and high density lipoprotein-cholesterol have been described, but in the existing literature these effects remain controversial because of inconsistencies. Moreover, the degree of change varies from study to study. Therefore, the present study completely investigated changes in lipids and lipoproteins throughout the pregnancy and in the puerperium. We also investigated whether or not any relation between plasma lipids and other pregnancy related factors exist. Concentrations of cholesterol and triglyceride of total plasma, and lipoproteins were determined in 56 pregnant women throughout the pregnancy and in the puerperium along with 56 non-pregnant women. Compared to control group, concentrations of cholesterol and triglyceride of total plasma and lipoproteins increased significantly during second trimester and reached maximum in the third trimester. Both cholesterol and triglyceride concentrations decreased significantly within 24 hours of delivery and this was reflected in all lipoproteins. In the majority of subjects, cholesterol and triglycerides remained significantly high until 4 weeks of postpartum. The magnitude of the serum cholesterol increment appeared in part to be related to that of serum triglyceride, but these increments appeared to be independent of age, weight gain, numbers of previous pregnancies and sex of the fetus. This study concludes that hyperlipidemia is a common finding during pregnancy.

Arteriosclerosis↗

Transdermal delivery of sodium nonivamide propionate by iontophoresis.

The aim of this study was to investigate the transdermal iontophoresis of a newly designed capsaicin derivative, sodium nonivamide propionate (SNP). The iontophoretic permeation of SNP from various pH buffers increased following the decrease of pH values. This trend was consistent with that of sodium nonivamide acetate (SNA) which is another synthetic analogue of capsaicin. However, the iontophoretic permeability of SNP was much lower than that of SNA. SNP was also delivered iontophoretically from hydrogel formulations. It is suggested that ionizable polymers should be avoided for iontophoretic delivery to maintain good penetration capacity of drugs. Both nonionic cellulose polymers of methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC) showed higher iontophoretic flux for SNP than the others did. Furthermore, the flux of SNP leveled off with an increase in the amount of polymers in hydrogel, indicating that the viscosity of vehicles plays an important role in the permeation of SNP. Comparing the various iontophoretic application modes, the discontinuous on/off cyclic mode showed higher penetration capacity than did the continuous mode although they possessed the same electrical energy. Moreover, the desorption time of SNP from skin was approximately 20 min which was longer than that of SNA.

Administration, Cutaneous↗

Percutaneous absorption of captopril from hydrophilic cellulose derivatives through excised rabbit skin and human skin.

The purpose of this investigation was to evaluate the influence of percutaneous absorption of captopril from hydrophilic cellulose derivatives gel bases (carboxymethylcellulose sodium [CMC], hydroxypropylcellulose [HPC] and hydroxylpropylmethylcellulose [HPMC]. The effects of various types and concentrations of penetration enhancers on captopril percutaneous absorption from HPC gel through rabbit skin were evaluated and selected to obtain some optimal formulations for penetration study through human chest skin. Then the required flux (1488 microg/hr) for captopril transdermal drug delivery system to maintain the therapeutic minimum effective concentration through human skin was used to evaluate the development of the optimal formulations. The results indicated that the minimum administered areas for therapeutic minimum effective concentration of captopril (cap) gel containing decanol (dec) were 10.4 cm2 (5% cap, 7% dec) and 7.6 cm2 (7% cap, 7% dec). These areas were within acceptable range, so these formulations can possibly be developed for a transdermal drug delivery system.

Administration, Cutaneous↗

Variations in ocular pressure during menstrual cycle.

The present study investigated whether a correlation between days of the menstrual cycle and variations in intraocular pressure exists or not. The number of days since the beginning of last menses was recorded along with intraocular pressure for 1,459 women. Measurements were taken by Goldmann applanation tonometer. The differences among various days of menstrual cycle were statistically insignificant. The highest mean IOP occurred between 20th and 22nd day and the second peak from 13th to 15th days of the cycle. The lowest mean IOP was found from 16th to 19th days of the cycle. This study concludes that intraocular pressure varies with the various days of the menstrual cycle, but fluctuations are statistically insignificant and cannot affect the diagnoses of glaucoma.

Female↗

Topical application of clobetasol 17-propionate from various cream bases by using Wistar rat as an animal model.

The effect of clobetasol 17-propionate (CP), a potent corticosteroid, participating in various cream bases on the permeation through rat skin was tested in vitro. Three commercially available formulations and three cream bases prepared in our laboratory according to Pharmacopoeia or registered patent were evaluated in this present study. The amount of CP in the receptor phase of diffusion cell was negligible in the beginning of administration due to the process of saturation of drug in skin reservoir, then the CP molecules pass through the skin directly because of the saturation of receptors in skin reservoir followed the higher flux of CP in the later period. It was suggested that the incorporation of penetration enhancers was the possible reason mainly controlling the flux of CP creams. Nevertheless, CP residue in skin and the lag time of formulations prepared in our laboratory were not significantly higher than those of commercial ones, which indicated penetration enhancer could not dominate the local pharmacological effectiveness of CP though they played a main part on the skin penetration capacity of formulations. The antiinflammatory activity of CP was assessed in the ear of Wistar rat. According to the result of antiinflammatory activity, all formulations showed significant inhibition on oedema suggesting the role of drug itself may be more important than that of vehicle in controlling the therapy efficacy.

Administration, Topical↗