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Biomedical subjects

Chi-Feng Hung

Publications and source records attributed to Chi-Feng Hung.

At least 19 recordsLinked to original sources
PubMed2006

The effect of oil components on the physicochemical properties and drug delivery of emulsions: tocol emulsion versus lipid emulsion.

An emulsion system composed of vitamin E, coconut oil, soybean phosphatidylcholine, non-ionic surfactants, and polyethylene glycol (PEG) derivatives (referred to as the tocol emulsion) was characterized in terms of its physicochemical properties, drug release, in vivo efficacy, toxicity, and stability. Systems without vitamin E (referred to as the lipid emulsion) and without any oils (referred to as the aqueous micelle system) were prepared for comparison. A lipophilic antioxidant, resveratrol, was used as the model drug for emulsion loading. The incorporation of Brij 35 and PEG derivatives reduced the vesicle diameter to <100nm. The inclusion of resveratrol into the emulsions and aqueous micelles retarded the drug release. The in vitro release rate showed a decrease in the order of aqueous micelle system>tocol emulsion>lipid emulsion. Treatment of resveratrol dramatically reduced the intimal hyperplasia of the injured vascular wall in rats. There was no significant difference in this reduction when resveratrol was delivered by either emulsion or the aqueous micelle system. The percentages of erythrocyte hemolysis by the emulsions and aqueous micelle system were approximately 0 and approximately 10%, respectively. Vitamin E prevented the aggregation of emulsion vesicles. The mean vesicle size of the tocol emulsion remained unchanged during 30 days at 37 degrees C. The lipid emulsion and aqueous micelle system, respectively, showed 11- and 16-fold increases in vesicle size after 30 days of storage.

Animals↗
PubMed2006

(+)-Catechin prevents ultraviolet B-induced human keratinocyte death via inhibition of JNK phosphorylation.

High levels of (+)-catechin are found in the skin and seed of many fruits such as apples and grapes. Dietary supplementation with (+)-catechin has been demonstrated to protect epidermal cells against damage induced by ultraviolet B (UVB) radiation. However, the underlying mechanisms are not well understood yet. To determine whether (+)-catechin protects keratinocytes from UVB-induced damage, the viability of UVB- and H2O2-treated cells was determined by cell viability assay. Intracellular H2O2 level was measured by flow cytometry. UVB- or H2O2-induced signaling pathways were detected by Western blotting. The results indicated that (+)-catechin inhibited UVB- and H2O2-induced keratinocyte death. In parallel, intracellular H2O2 generation in keratinocytes irradiated by UVB was inhibited by (+)-catechin in a concentration-dependent manner. (+)-Catechin also inhibited UVB- and H2O2-induced JNK activation in keratinocytes. However, it had little inhibitory effect on UVB- and H2O2-induced ERK and p38 activation even at a higher concentration, suggesting indirectly that JNK activation is required for the induction of apoptosis in keratinocytes exposed to UVB. Finally, we compared the cytotoxicity of (+)-catechin and (-)-epigallocatechin-3-gallate (EGCG) on keratinocytes. Cell viability assay showed that (+)-catechin was relatively nontoxic at higher doses. Taken together, our results demonstrate that (+)-catechin inhibits UVB- and oxidative stress-induced H2O2 production and JNK activation and enhances human keratinocyte survival. However, although it seems that (+)-catechin and EGCG are equally effective in preventing keratinocyte death, (+)-catechin is relatively nontoxic and thus is suitable for developing as an anti-ageing agent for skin care.

Catechin↗
PubMed2006

Extrapelvic endometriosis complicated with colonic obstruction.

Endometriosis is often seen in gynecology practice and is treated medically. However, intestinal involvement of endometriosis causing obstruction is relatively uncommon and is hard to differentiate from malignancy before surgery. Herein, we present a case of acute colonic obstruction caused by rectal endometriosis. Repeat colonoscopic biopsy and imaging studies could not differentiate the lesion from malignancy. Segmental resection with anastomosis was performed to relieve the symptom and confirm the diagnosis. We present this unusual disease in general surgical practice and also review the literature. The incidence, symptoms, diagnosis, treatment, and risk of malignancy of intestinal endometriosis are discussed.

Adult↗
PubMed2006

E-cadherin and its downstream catenins are proteolytically cleaved in human HaCaT keratinocytes exposed to UVB.

It has been reported that ultraviolet B (UVB) irradiation causes the loss of E-cadherin of melanocytes, leading them to escape from neighboring keratinocytes during melanoma development. However, little has been paid on its effect on E-cadherin of keratinocytes. In the present study we therefore focus on whether UVB affects expression of E-cadherin-catenin complex in human HaCaT keratinocytes. We found that E-cadherin, beta-, and gamma-catenin but not alpha-catenin were proteolytically cleaved in UVB-irradiated HaCaT keratinocytes. The effect was only observed in keratinocyte undergoing apoptosis. Cleavage of beta- and gamma-catenin was fully abolished by caspase-3 and caspase-8 inhibitors, whereas cleavage of E-cadherin was inhibited by neither caspase nor metalloproteinase inhibitors. Functional analysis showed that the cleavage resulted in the disruption of the physical association between E-cadherin and catenins, indicating that E-cadherin signaling was compromised in UVB-irradiated HaCaT keratinocytes. Because E-cadherin in keratinocytes plays important roles in mediating cell-cell adhesion in epidermis of skin, the loss of E-cadherin and signaling components in keratinocytes may lead to the disruption of skin integrity after UVB exposure.

Apoptosis↗
PubMed2005

(-)-Epigallocatechin-3-gallate, a polyphenolic compound from green tea, inhibits fibroblast adhesion and migration through multiple mechanisms.

It is increasingly evident that the stromal cells are involved in key metastatic processes of melanoma and some malignant solid tumors. (-)-Epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, has been shown to have anti-tumor activity, inhibiting adhesion, migration, and proliferation of tumor cells. However, little attention has been paid on its effects on stromal cells. In the present study, we determined the effects of EGCG on stromal fibroblasts. We showed that fibroblast adhesion to collagen, fibronectin, and fibrinogen were inhibited by EGCG. One of the possible mechanisms is binding of EGCG to fibronectin and fibrinogen but not to collagen. We then focused how EGCG affected fibroblast adhesion to collagen. EGCG treatment attenuated the antibody binding to fibroblast's integrin alpha2beta1, indicating EGCG may affect the expression and affinity of integrin alpha2beta1. Moreover, intracellular H2O2 level was decreased by EGCG treatment, suggesting that the tonic maintenance of intracellular H2O2 may be required for cell adhesion to collagen. In parallel, collagen-induced FAK phosphorylation, actin cytoskeleton reorganization in fibroblasts, migration and matrix metalloproteinase(s) (MMPs) activity were also affected by EGCG. Tubular networks formed by melanoma cells grown on three-dimensional Matrigel were also disrupted when fibroblasts were treated with EGCG in a non-contact coculture system. Taken together, we provided here the first evidence that EGCG is an effective inhibitor on behaviors of the stromal fibroblasts, affecting their adhesion and migration. The inhibitory activity of EGCG may contribute to its anti-tumor activity. The findings and concepts disclosed here may provide important basis for a further experiment towards understanding tumor-stroma interaction.

Actins↗
PubMed2005

Antiinflammatory flavonoids from Artocarpus heterophyllus and Artocarpus communis.

The antiinflammatory activities of the isolated flavonoids, including cycloartomunin (1), cyclomorusin (2), dihydrocycloartomunin (3), dihydroisocycloartomunin (4), cudraflavone A (5), cyclocommunin (6), and artomunoxanthone (7), and cycloheterohyllin (8), artonins A (9) and B (10), artocarpanone (11), artocarpanone A (12), and heteroflavanones A (13), B (14), and C (15) from Artocarpus communis and A. heterophyllus, were assessed in vitro by determining their inhibitory effects on the chemical mediators released from mast cells, neutrophils, and macrophages. Compound 4 significantly inhibited the release of beta-glucuronidase and histamine from rat peritoneal mast cells stimulated with P-methoxy-N-methylphenethylamine (compound 48/80). Compound 11 significantly inhibited the release of lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP). Compounds 8, 10, and 11 significantly inhibited superoxide anion formation in fMLP-stimulated rat neutrophils while compounds 2, 3, 5, and 6 evoked the stimulation of superoxide anion generation. Compound 11 exhibited significant inhibitory effect on NO production and iNOS protein expression in RAW 264.7 cells. The potent inhibitory effect of compound 11 on NO production in lipopolysaccharide (LPS)-activated macrophages, probably through the suppression of iNOS protein expression.

Animals↗
PubMed2005

Protective effects of (-)-epicatechin-3-gallate on UVA-induced damage in HaCaT keratinocytes.

(-)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been extensively studied and shown to be a powerful antioxidant protecting skin cells against photodamage. In this study, however, we demonstrated that another gallated catechin, (-)-epicatechin-3-gallate (ECG), was also able to protect human keratinocytes against damage induced by ultraviolet A (UVA) light. We found that ECG dose-dependently inhibited UVA-induced keratinocyte death as determined by cell viability assay. Moreover, ECG had similar potency to EGCG in inhibiting UVA-induced cell death. Therefore, the mechanism of action of ECG was further investigated. As assayed by flow cytometry, UVA-induced hydrogen peroxide (H2O2) production in keratinocytes was inhibited by ECG in a concentration-dependent manner, suggesting that ECG can act as a free radical scavenger while keratinocytes were photodamaged. The scavenging effect of ECG was confirmed by the fact that ECG treatment attenuated cell damage induced by H2O2 and hypoxanthine-xanthine oxidase. In a parallel experiment, UVA-induced activation of extracellular signal-regulated kinase in keratinocytes was blocked by ECG. We provided here the first evidence that ECG is a potent protectant that protects keratinocytes from photodamage. Because ECG is abundant in green tea, we believe that this compound is beneficial for skin care.

Antioxidants↗
PubMed2005

Extended-field radiotherapy and high-dose-rate brachytherapy with concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer: a phase I/II study.

OBJECTIVE: The purpose of this prospective study was to investigate the toxicity and efficacy of integrating extended-field para-aortic and pelvic external radiation, high-dose-rate intracavity brachytherapy, and concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer. METHOD: A phase I/II study was performed from 1998 to 2003 including sixty-three patients with both clinical FIGO and MRI/CT-based TNM stage IIB-IVA cervical cancer. Patients were treated with extended-field external radiation to the para-aortic and pelvic regions with 45 Gy in 25 fractions, and an additional boost to the gross nodes to 50.4 Gy and the parametrium to 59.4 Gy. Patients also received a high-dose-rate (HDR) intracavity brachytherapy with doses of 22-31 Gy to point A in 4-6 fractions. Concurrently, two cycles of cisplatin (50-80 mg/m(2)) were administered in weeks 1 and 5 during radiotherapy, as well as two cycles of cisplatin (60-80 mg/m(2)) for 1 day and 5-fluorouracil (600-800 mg/m(2)) for 4 days at 1 and 2 months after completion of radiotherapy. The treatment-related acute and late side effects were evaluated using RTOG criteria, and the disease control and survival rate were calculated using the Kaplan-Meier method. The median follow-up interval was 36 months. RESULTS: All sixty-three patients completed the planned extended-field radiotherapy and high-dose-rate brachytherapy with 2 concurrent cycles of cisplatin. Fifty-eight (92%) patients received 2 cycles of the post-radiation adjuvant chemotherapy of cisplatin and 5-fluorouracil. RTOG grade III acute toxicity was gastrointestinal (2%) and hematological (10%). No patient had grade IV acute toxicity. Late grades III-IV morbidity actuarial risk of 6% at 6.5 years primarily involved the injuries to the bowels requiring surgical intervention for intestinal obstruction or fistula formation. Initial sites of recurrence were locoregional failure alone (pelvic and para-aortic regions within the radiation field), 3%; distant metastases only, 8%; and locoregional failure plus distant metastases, 8%. The observed rates at 3-year and 5-year of locoregional control, freedom from distant metastasis, and overall survival were 86% and 86%, 81% and 81%, and 81% and 77%, respectively. CONCLUSION: Incorporating HDR brachytherapy into a regimen including concurrent chemotherapy and extended radiation appears safe and effective.

Adult↗
PubMed2005

Physicochemical characteristics and in vivo deposition of liposome-encapsulated tea catechins by topical and intratumor administrations.

Tea polyphenols, including (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin-3-gallate (EGCG), have been shown to possess potent antioxidant and anticancer activities. The aim of this study was to evaluate the possibility of using liposomes for the local delivery, including skin and tumor deposition, of these polyphenols. Liposomes containing egg phosphatidylcholine, cholesterol, or anionic species were prepared by a solvent evaporation method and then were subjected to a probe sonicator. The size, zeta potential and entrapment efficiency of these liposomal formulations were determined to provide correlations with results from a subsequent in vivo study. The release rate study showed that inclusion of an anionic species, such as deoxycholic acid (DA) or dicetyl phosphate (DP), increased the permeability of the lipid bilayers, leading to the rapid release of these formulations. No significant increase in skin deposition of catechins was observed after topical application of liposomes. On the other hand, a greater amount of catechins were delivered into the solid tumor by liposomes than by the aqueous solution. The drug release rate and vesicle size of liposomes may influence drug deposition in tumor tissues. The isomers, (+)-catechin and (-)-epicatechin, showed different physicochemical properties in liposomes and for local deposition in the skin and tumor. Finally, the presence of gallic acid ester in the structure of EGCG significantly increased the tissue uptake of catechins.

Administration, Topical↗
PubMed2004

Physicochemical characterization and gene transfection efficiency of lipid emulsions with various co-emulsifiers.

Transfection systems based on complexes of DNA and lipid emulsions were evaluated with respect to their effectiveness, toxicity, physicochemical characteristics, and cell-type dependence. The potential of a series of co-emulsifiers to serve as vectors was investigated. The co-emulsifiers examined included 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), Tween, cholesterol, stearylamine, and polyethylenimine (PEI). Squalane and 1,2-dioleoyl-sn-glycero-3-trimethylammonium-propane (DOTAP), respectively, were the main oil phase and cationic lipid added to the lipid emulsions. Cell viability was reduced after inclusion of either of the two cationic components of stearylamine and PEI. DOPE and cholesterol showed both higher transfection activity and cell viability as compared to the other co-emulsifiers. The incorporation of DOPE and cholesterol also prevented droplet aggregation of the emulsions after long-term storage. Results of the transfection of COS-1, A549, or HaCat cell lines with lipid emulsions indicated differences in transfection activities of each formulation for the different cell lines. It is concluded that DOPE and cholesterol as co-emulsifiers for DOTAP were preferable for stability and DNA transfection of emulsions.

Animals↗
PubMed2004

Transdermal iontophoresis of 5-fluorouracil combined with electroporation and laser treatment.

The influence of iontophoresis and other physical enhancement methods such as electroporation and erbium:yttrium-aluminum-garnet (YAG) laser on the skin permeation of 5-fluorouracil (5-FU) was examined. Iontophoresis increased the in vitro transdermal transport of both the anionic and non-ionic forms of 5-FU. A combination of electroporation pretreatment and subsequent iontophoresis resulted in a higher permeation of 5-FU than either technique alone. It appeared that electroporation treatment exerted a disruptive influence on the stratum corneum (SC). The SC layers in the skin were partly ablated by the laser, resulting in a great enhancement effect on the skin permeation of 5-FU. Application of iontophoresis further increased the drug permeation across laser-pretreated skin. The laser was consistently the most potent technique to enhance 5-FU delivery among the physical enhancement methods examined in this study.

Administration, Cutaneous↗
PubMed2004

Morphine inhibits glutamate exocytosis from rat cerebral cortex nerve terminals (synaptosomes) by reducing Ca2+ influx.

Morphine, a mu-opioid agonist, suppressed the Ca(2+)-dependent release of glutamate that was evoked by exposing cerebrocortical synaptosomes to the potassium channel blocker 4-aminopyridine. The presynaptic inhibition produced by morphine was concentration-dependent and blocked by the nonselective opioid receptor antagonist naloxone. As determined by examining the mechanism of mu-opioid receptor-mediated inhibition of glutamate release, morphine caused a significant reduction in 4-aminopyridine-evoked increase in the cytoplasmic free Ca(2+) concentration ([Ca(2+)](c)), but failed to alter both 4-aminopyridine-evoked depolarization of the synaptosomal plasma membrane potential and Ca(2+) ionophore (ionomycin)-induced glutamate release. In addition, morphine was not capable of producing further inhibition on 4AP-evoked glutamate release in synaptosomes pretreated with the cannabinoid CB(1) receptor agonist WIN 55212-2, which has been shown to depress glutamate release through a suppression of presynaptic voltage-dependent Ca(2+) channel activity. These data suggest that morphine exerts its inhibitory effect presynaptically, likely through the reduction of Ca(2+) influx into nerve terminals, and thereby inhibits the release of glutamate in the cerebral cortex. This may therefore indicate that mu-opioid receptor agonists have neuroprotective properties, especially in the excessive glutamate release that occurs under certain pathological conditions.

4-Aminopyridine↗
PubMed2004

Development and evaluation of the essential oil from Magnolia fargesii for enhancing the transdermal absorption of theophylline and cianidanol.

To improve the skin permeation of theophylline and cianidanol ((+)-catechin), the essential oil of Magnolia fargesii was evaluated using in-vitro and in-vivo permeation techniques. Oxygenated monoterpenes and sesquiterpenes are the major components of M. fargesii essential oil. The in-vitro permeation of theophylline and cianidanol was significantly enhanced after treatment with M. fargesii essential oil. The essential oil increased the in-vivo skin deposition of cianidanol but not theophylline. On the other hand, in-vivo microdialysis showed a higher subcutaneous theophylline amount after essential oil treatment. In-vitro cell viability and prostaglandin E(2) release by skin keratinocytes indicated that there was low or negligible cytotoxicity by M. fargesii essential oil. The in-vivo skin tolerance study determined by transepidermal water loss and colorimetry confirmed that no irritation of the skin was detected when using M. fargesii essential oil.

Administration, Cutaneous↗
PubMed2003

Single-point plasma or urine dextromethorphan method for determining CYP3A activity.

Dextromethorphan is used widely in vivo to phenotype the polymorphically expressed cytochrome P450 (CYP) 2D6. Also dextromethorphan is N-demethylated in vivo to 3-methoxymorphinan by human CYP3A4/5. The metabolic ratio (MR) of dextromethorphan/3-methoxymorphinan in plasma, saliva and urinary were examined as a possible in vivo probe of CYP3A activity. In limited previous studies, 4 h urinary samples were collected for determining the MR. To evaluate the repeatability and validity of previously reported and other potential phenotyping methods, the MR from urine samples (at various intervals), from plasma and from saliva (at varying time points) were determined after repetitive single doses of immediate-release or repetitive multiple doses of controlled-release dextromethorphan preparations. For the single-dose study, each of 12 subjects received 15 mg of immediate-release dextromethorphan in periods II and I, respectively, with a 1 week washout period. For the multiple dose study, each of 16 subjects received 60 mg controlled release dextromethorphan twice daily for 5 days in periods I and II, respectively, with a 2 week washout period. Dextromethorphan and 3-methoxymorphinan are assayed by high-performance liquid chromatography. In the single-dose study, all of the urine MR revealed good repeatabilities for the periods (paired t-test). The urine MR at any time interval of 0-6 h, 0-8 h and 0-12 h correlated significantly with the MR from 0-24 h urine (r>0.8, p<0.05). In the multiple-dose study, all MR revealed good repeatabilities for the two periods (paired t-test). The plasma MR at any time between 0.5 h and 12 h, the saliva MR at 12 h and the urine MR at any interval between 0-2 h, 0-4 h, 0-6 h, 0-8 h, 0-12 h and 0-24 h could predict the MR from AUCtau(ss). In conclusion, the urine sample as 0-6 h, 0-8 h or 0-12 h in the single immediate-release dose (15 mg) or in the multiple controlled-release dose (60 mg) procedure, the saliva sample at 12 h, the urine sample at 0-2 h, 0-4 h, 0-6 h, 0-8 h, 0-12 h, 0-24 h or all plasma-sampling points 0.5-12 h could be used as the dextromethorphan MR for determining the CYP3A activity.

Administration, Oral↗
PubMed2003

Development of sesquiterpenes from Alpinia oxyphylla as novel skin permeation enhancers.

To improve the drug permeation into and/or across the skin, essential oils extracted from Alpinia oxyphylla (AO) were evaluated using in vitro and in vivo permeation techniques with Wistar rats as the animal model. Hydrocarbons and oxygenated sesquiterpenes were the major components in the lower-polarity fraction (AO-1) and higher-polarity fraction (AO-2), respectively. Permeation of indomethacin was significantly enhanced after treatment with AO-1 and AO-2 in the in vitro and in vivo studies. AO-2 generally showed a higher ability to promote drug permeation compared to AO-1. The increment of skin/vehicle partitioning may be the predominant mechanism for this enhancing activity. Both transepidermal water loss (TEWL) and colorimetric evaluation showed limited irritation to skin by AO essential oils at the macroscopic level. Human skin fibroblasts were used to investigate the in vitro screening of skin toxicity. AO-1 slightly increased prostaglandin E(2) (PGE(2)) formation from skin fibroblasts. A striking result was observed with AO-2, which greatly inhibited the release of PGE(2). Moreover, both AO essential oils had no statistically significant effect on PGE(2) release by human lung epithelial cells. The results of this study indicate that skin disruption and inflammation do not necessary correspond to the enhancing efficiency of the enhancers tested.

Alpinia↗
PubMed2003

Efficacy and irritancy of enhancers on the in-vitro and in-vivo percutaneous absorption of curcumin.

Curcumin is a predominant compound derived from the rhizomes of Curcuma longa L., and shows antibacterial, anti-inflammatory and antineoplastic activity. The in-vitro and in-vivo skin absorption of curcumin was investigated after application of enhancers using Wistar rat as an animal model. The enhancers selected in this study included terpenes, flavonoids and cholestanol. The irritant profiles of these enhancers were also established by transepidermal water loss (TEWL) and histological observations. Cyclic monoterpenes generally showed stronger enhancement of curcumin permeation than the other enhancers. Modulation of concentration and pretreatment duration of enhancers possibly indicated that the enhancers have varied ability and mechanisms to enhance curcumin permeation. Terpineol produced the highest TEWL values among the enhancers tested, whereas ketocholestanol produced no, or only a negligible, increase in TEWL as compared with control. The results showed that skin disruption and inflammation did not necessarily correspond to the enhancing efficiency of the enhancers.

Administration, Cutaneous↗
PubMed2003

Zolpidem-induced distortion in visual perception.

OBJECTIVE: To describe a patient who developed visual perception distortion after a single dose of zolpidem. CASE SUMMARY: A 50-year-old Asian woman had been prescribed conjugated estrogen 1 tablet daily for hormone replacement therapy and tricalcium phosphate twice daily for osteoporosis. One day, she took zolpidem 10 mg for insomnia as well as acetaminophen 500 mg for headache at bedtime and began to have visual perception distortion (e.g., the shapes of objects were twisted, houses were crooked) within 20 minutes, lasting for approximately 30 minutes, and then her vision returned to normal. She only partially recalled the event. She had never taken zolpidem before, and she had not had any such disturbances in the past. DISCUSSION: There have been 21 case reports of zolpidem-related psychotic symptoms in the literature; however, the exact mechanism by which zolpidem may cause visual perception changes is undetermined. Many factors have been correlated with zolpidem-induced visual experiences, such as pharmacokinetic factors, gender, age, and hypoalbuminemia. This patient shared certain similarities such as gender, dosage, and time of onset and duration of adverse reactions. CONCLUSIONS: An objective causality assessment revealed that the zolpidem-induced visual perception distortion in this patient was probable. Clinicians should be aware of the potential for visual perception distortion, as this is an uncommon adverse effect.

Female↗