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Biomedical subjects

B C Chung

Publications and source records attributed to B C Chung.

At least 37 records · Page 2Linked to original sources
PubMed2001

Development of rat prostatitis model by oral administration of isoflavone and its characteristics.

Inflammation of the prostate can be induced experimentally in rats by the subcutaneous administration of estrogen. However, it is usually achieved at the price of some alteration in the sex steroid hormone balance and morphological changes in the prostate. In this study, a soy-extracted isoflavone mixture with weak estrogenic activity was administered orally in an attempt to induce prostatitis in a more physiologic way and to characterize the inflammation induced. A total of 36 male Sprague-Dawley rats, 8 weeks old, were divided into 2 groups. The control group was fed with only an AIN-76A diet containing no detectable phytoestrogen and the experimental group was fed with AIN-76A and a soy- extracted isoflavone mixture (genistein 60.0% and daidzein 19.6%), 300 mg/kg body weight for 9 weeks. The sequential body weight and prostate weight at necropsy were measured. A histologic examination and histomorphometry assessed the changes in the prostate. The serum concentrations of testosterone and dihydrotestosterone were measured to estimate the effects on the androgen level. Intraprostatic concentrations of genistein and daidzein were measured by gas chromatography/ mass spectroscopy (GC/MS). While no sign of prostate inflammation was apparent in the control group, severe inflammatory changes in the stroma, increased epithelial detachment and inflammatory exudates within the glandular lumen of the dorsolateral prostate were observed in more than 80%(15/18) of the experimental group. However, there was no significant difference in the ventral prostate between the two groups. The daidzein and genistein concentrations in both the lateral and ventral prostates were significantly higher in the experimental group than in the control group where no isoflavone was detectable. In addition, the concentrations were much higher in the dorsolateral than in the ventral prostate. Although the body weight gain was not consistent in the experimental group, there were no significant differences in the prostate weight and serum androgen level between groups. In summary, when a soy-extracted genistein and daidzein-rich isoflavone mixture was administered orally into rats, prostatic inflammation with characteristic lobe specificity developed. The present method of inducing prostatitis seems to be a more physiologic than an estrogen-induced experimental model, and sequential pharmacokinetic studies might help in establishing this model as a more valuable tool in assisting future research in this field.

Administration, Oral↗
PubMed2001

Urinary profile of endogenous steroids in postmenopausal women with stress urinary incontinence.

OBJECTIVE: To predict the role of estrogen in prevention of and therapy for stress urinary incontinence by comparing the urinary levels of estrogens and androgens and, to indirectly evaluate metabolism of estrogens and androgens by comparing the concentration ratios of precursor metabolites with those in controls (normal subjects). STUDY DESIGN: Urine samples collected for 24 hours were obtained from postmenopausal women with stress urinary incontinence (n = 20) and from age-matched, postmenopausal, normal female subjects (n = 14). The urinary levels of 20 estrogens and 25 androgens were analyzed by gas chromatography/mass spectrometry. RESULTS: The urinary levels of androgens were significantly higher in patients with stress urinary incontinence than normal subjects, and the urinary levels of estrogens were somewhat higher in patients than normal subjects. However, there were no significant differences between the groups, nor were there significant differences in the metabolism of estrogens and androgens between two groups. CONCLUSION: The urinary levels of endogenous steroids were rather higher in patients with stress urinary incontinence than in normal subjects, so it appears that estrogen should not play a significant role in prevention of and therapy for stress urinary incontinence.

Age Factors↗
PubMed2000

Determination of hair polyamines as N-ethoxycarbonyl-N-pentafluoropropionyl derivatives by gas chromatography-mass spectrometry.

An efficient method is described for the simultaneous determination of hair polyamines, such as 1,3-diaminopropane, putrescine, cadaverine, spermidine and spermine, by gas chromatography-mass spectrometry (GC-MS) with the selected ion-monitoring (SIM) mode. The method is based on the extractive two-phase ethoxycarbonyl (EOC) reaction of amino functions in aqueous solutions combined with subsequent pentafluoropropionyl (PFP) derivatization of the remaining active hydrogen atoms for the direct analysis by GC-SIM-MS. The detection limits for SIM of the polyamines as N-EOC-N-PFP derivatives ranged from 1 to 10 ng/g hair, while their recovery rates varied in the range of 76.42-93.38%. This method demonstrated a good overall accuracy (% bias) and precision (% C.V.) as 3.32-11.05% and 5.88-14.71%, respectively. When applied to 0.6 M HCl extracts of hair samples from 11 healthy men and 19 healthy women, all five polyamines were positively detected at the concentrations of 8.82-871.87 ng/g. Both in median and mean concentrations, the most abundant hair polyamine was spermidine, followed by spermine, putrescine, 1,3-diaminopropane and cadaverine in the male group, while the order of 1,3-diaminopropane and cadaverine was reversed in the female group. The levels of polyamines, except for cadaverine, in hair specimens studied were found to be higher in men than in women.

Adult↗
PubMed2000

In Planta visual monitoring of green fluorescent protein in transgenic rice plants.

The green fluorescent protein (GFP) from the jellyfish Aequorea victoria is a widely used reporter that can be directly visualized in the living cells in both animals and plants. We inserted a synthetic gene (sgfp) encoding a modified form of the GFP into expression vector, Act1-sgfp for the direct expression of GFP which is easily detectable in rice plants. Green fluorescence emitted from GFP could be visualized in calli, dry seeds, roots and seedlings with green shoots of transgenic rice plants. In our visualization system with a charge-coupled device camera, band-pass filters and a light source, the presence of red chlorophyll autofluorescence from chloroplasts did not alter the green fluorescence of GFP. These results demonstrate that GFP could be used as a non-destructive visual selection marker for examining gene expression in transformed calli, dry seeds and young plants.

Gene Expression↗
PubMed2000

Gas chromatographic-mass spectrometric determination of plasma saturated fatty acids using pentafluorophenyldimethylsilyl derivatization.

An improved method for the detection of 11 saturated fatty acids (SFAs) including C12:0-C26:0 (even numbers only), C17:0, C19:0 and C23:0 in human plasma by gas chromatography-mass spectrometry (GC-MS) with a stable isotope internal standard as d3-stearic acid is described. This procedure was based on acidic treatment, liquid-liquid extraction, and chemical derivatization prior to instrumental analysis. Eleven pentafluorophenyldimethylsilyl-SFA derivatives were well separated without any interfering peaks in plasma samples. The characteristic ions at M-15, constituting the base peaks in the electron impact mass spectra for 11 SFAs, permitted their sensitive detection by GC-MS in the selected ion monitoring (SIM) mode. The SIM responses were linear with correlation coefficients varying from 0.993 to 0.999 in the concentration range of 0.05 to approximately 50 microg/ml for the 11 SFAs. The detection limits for SIM of the SFAs varied in the range of 0.05 to approximately 10.0 pg. When applied to the plasma samples of normal subjects and patients with X-linked adenoleukodystrophy, which is one of the hereditary peroxisomal disorders, the present method enabled us to determine the SFAs with good sensitivity and good overall precision and accuracy within the concentration ranges of 0.14 to approximately 82.35 micromol/l.

Adolescent↗
PubMed2000

Prolonged delivery of nicotine in rats via nasal administration of proliposomes.

In order to achieve a prolonged delivery of nicotine to the systemic circulation, proliposomes containing nicotine base (NB-proliposomes) or nicotine hydrogen tartarate salt (NS-proliposomes) and a mixture of powdered nicotine hydrogen tartarate salt and sorbitol (1:9 mixture, MP) were administered intranasally to rats at a nicotine dose of 1 mg/kg. Proliposomes, lipid-sorbitol mixtures that form liposomes upon contact with water, were prepared according to previously established methods, and the mixture (MP) was prepared by mixing NS powder with sorbitol particles (105-350 micrometer in size). Nasal absorption of nicotine from these formulations was very rapid (i.e. less than 10 min was required to reach plasma peaks) and showed substantially sustained plasma nicotine levels compared to saline solutions of NB and NS, and previously reported nasal nicotine sprays. The AUC values from the proliposomes and MP were comparable to those from the saline solutions of NB and NS. However, the mean residence time (MRT) and plasma half-life (T(1/2beta)) of nicotine in the present study were much larger than those from the saline solutions. Thus, a prolonged delivery of nicotine to systemic circulation via the application of proliposomes or MP intranasally appears feasible. NB-proliposomes exhibited the best characteristics in terms of the area under the plasma concentration (AUC), MRT and T(1/2beta) of nicotine, which was followed by NS-proliposomes and MP. Retarded conversion of proliposomes and MP to liposomal emulsions and solution in the nasal cavity seems responsible, in part, for the sustained plasma nicotine concentrations, since the emulsions and solution yielded very short MRT and T(1/2beta) of nicotine. In addition, reduced metabolism to cotinine from the proliposomes and MP was apparently responsible for the sustained plasma nicotine levels. These dosage forms of nicotine appear to circumvent some of the shortcomings of transdermal patches (i.e. long T(max)) and nasal sprays (i.e. short T(1/2beta) and physicochemical instability).

Administration, Intranasal↗
PubMed2000

Measurement of 19-nortestosterone and its esters in equine plasma by high-performance liquid chromatography with tandem mass spectrometry.

A high-performance liquid chromatographic-tandem mass spectrometric (HPLC/MS/MS) method for the determination of 19-nortestosterone and its esters (cyclopentanepropionate, phenylpropionate, and decanoate) in equine plasma is achieved using an atmospheric pressure chemical ionization (APCI) interface in selected reaction monitoring (SRM) mode. The two internal standards used were 16,16, 17-(2)H(3)-19-nortestosterone for 19-nortestosterone and methenolone acetate for its esters. The steroids studied were extracted from plasma samples with a mixture of diethyl ether/n-hexane (9:1, v/v). The quantification limits for 19-nortestosterone, 19-nortestosterone cyclopentanepropionate, 19-nortestosterone phenylpropionate, and 19-nortestosterone decanoate were 0.16, 5.0, 0.1, and 2.0 ng/mL, respectively, when 2 mL of plasma were used. The recoveries of most of the steroids were 71.6-101.0% except for the decanoate, which could be recovered to about 39.8%. The responses were linear, with correlation coefficients varying from 0.9897 to 0.9999 in the concentration range of 0.1 to 50.0 ng/mL for the steroids studied. When applied to equine (mare) plasma samples, the present method allowed detection of 19-nortestosterone up to 23 days after an intra-muscular injection of 400 mg as the decanoate.

Anabolic Agents↗
PubMed2000

Simultaneous determination of urinary androgen glucuronides by high temperature gas chromatography-mass spectrometry with selected ion monitoring.

An efficient procedure is described for the simultaneous determination of 9 androgen glucuronides including androsterone, etiocholanolone, 11-ketoandrosterone, 11-ketoetiocholanolone, 11beta-hydroxyandrosterone, 11beta-hydroxyetiocholanolone, and dehydroepiandrosterone (DHEA) in 3-glucuronide form and dihydrotestosterone (DHT) and testosterone in 17-glucuronide form from urine specimens. The method involves solid-phase extraction of the urinary steroids using Serdolit PAD-1 resin, with subsequent conversion to methyl ester-trimethylsilyl (Me-TMS) ether derivatives for the direct analysis by gas chromatography-mass spectrometry (GC-MS) using high temperature MXT-1 (Silcosteel-treated stainless steel) capillary column. Upon split injection of Me-TMS steroids at 330 degrees C into the MXT-1 capillary column initially maintained at 300 degrees C then programmed to 322 degrees C at 2 degrees C/min, each androgen glucuronide was well separated in excellent peak shape. The characteristic ions at m/z 217 constituting the base peaks in the electron-impact (20 eV) mass spectra for most steroids permitted their sensitive detection by GC-MS with selected-ion monitoring (SIM), whereas base peak ion at m/z 271 was used for the SIM of dehydroepiandrosterone-3-glucuronide. The detection limits for SIM of most of the steroids were 15 pg except for the 3-glucuronides of 11-ketoandrosterone and 11-ketoetiocholanolone, which could be detected down to 20 pg. The SIM responses were linear with correlation coefficients varying from 0.981 to 0.993 in the concentration range of 20 to 3000 ng/ml for the androgens studied. When applied to urine samples, the present method allowed rapid screening for the 7 androgens in their glucuro-conjugated forms simultaneously with good overall precision and accuracy within the normal concentration ranges of 15.1 to 3124.6 ng/ml.

Androgens↗
PubMed2000

Determination of estrone and 17 beta-estradiol in human hair by gas chromatography-mass spectrometry.

An efficient procedure is described for the determination of estrone and 17 beta-estradiol in hair by gas chromatography-mass spectrometry (GC-MS). The method involves alkyloxycarbonylation with isobutyl chloroformate (isoBCF) of phenolic hydroxy groups after alkaline digestion of hair samples. The resulting isobutyloxycarbonyl derivatives of estrone and 17 beta-estradiol are extracted with hexane and subjected to chlorodifluoroacetyl derivatization in order to protect the remaining alcoholic hydroxy groups. When GC-MS with selected ion monitoring (SIM) was used, the quantitative ions were at m/z 270 and 384 in the electron ionization mass spectra for estrone and 17 beta-estradiol, respectively. The detection limits for SIM of the steroids were 1 and 2 pg, respectively, and the SIM responses were linear with correlation coefficients varying from 0.991 to 0.994 in the concentration range 0.2-4.0 ng g-1 for the estrogens studied. The detection of estrone and 17 beta-estradiol in hair samples was possible in the concentration range of 0.24-1.30 ng g-1. The concentrations of the two estrogens detected were different in male and female hair samples.

Adult↗
PubMed2000

Pharmacokinetics and urinary excretion of DW116, a new fluoroquinolone antibacterial agent, in humans as a phase I study.

Pharmacokinetics and urinary excretion of the new fluoroquinolone antibacterial agent DW116 [1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazynyl)-1, 4-dihydro-4-oxoquinolone-3-carboxylic acid, hydrochloride] following oral administration (200, 400, 600 mg) were studied in humans as a phase I study. The plasma concentration of DW116 declined monoexponentially with a half-life range of 16-22 hr. The area under the curve (AUC) and Cmax increased proportionally as the dose increased. The T1/2 and mean residence time (MRT) (28.3-30.9 hr) were independent of dose. The Tmax appeared within 3 hr (0.9-2.7 hr) after drug administration. The Ka ranged from 1.3 to 4.1 (hr-1). The plasma half-life was much longer, and Cmax was higher by about two- to three-fold than conventional fluoroquinolones. Urinary recovery of DW116 was 29.6-61.6% of the dose. The maximum excretion rate appeared within 4 hr and decreased continuously after drug administration. A urinary metabolite was not detected in the urine extract obtained before and after hydrolysis by beta-glucuronidase (from Escherichia coli); this was different from other fluoroquinolone antibacterial agents. Poor metabolism in the kidney may contribute to the good oral bioavailability, but due to the low recovery (< 60%) in urine, it is possible that DW116 is metabolized in the liver or other organs.

Adult↗
PubMed2000

Carrier analysis and prenatal diagnosis of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency in Chinese.

Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase (CYP21) gene. We screened 1,000 healthy people, using a previously developed differential PCR method combined with single-strand conformation polymorphism and amplification-created restriction site methods for the carrier detection of the CYP21 gene deficiency. Our results indicated that the rate of occurrence of the heterozygous CAH carrier was about 12 in 1,000, with a gene frequency of 0.0060 and an incidence frequency of 1 in 28,000 in the Chinese population. In addition, 9 cases of CAH families were performed with prenatal diagnosis. Among them, 3 cases were diagnosed as the severe form, 4 cases carried the heterozygous mutation, and 2 were normal. This is the first report of carrier frequency analysis and prenatal diagnosis of 21-hydroxylase deficiency in Chinese.

Adrenal Hyperplasia, Congenital↗
PubMed1999

Characterization of the consequence of a novel Glu-380 to Asp mutation by expression of functional P450c21 in Escherichia coli.

P450c21 catalyzes an important step in steroid synthesis. Its deficiency leads to symptoms of steroid imbalance. To obtain enough P450c21 for structure and function studies, we developed a method to express P450c21 in Escherichia coli. The 5'-region of the human P450c21 cDNA was modified to ensure efficient translation and the C terminus of the protein was extended with four His residues for easy purification. Mutant proteins with substitutions at residues 172 and 281 exhibited decreased enzymatic activities similar to those found in mammalian cells. One new mutation changing Glu-380 to Asp (D380) caused 3-fold reduction in enzymatic activity. The amount of apoprotein production detected by immunoblotting and the affinity of the mutant protein towards substrate as measured by Km were normal. The defect lies in the decreased ability of the apoprotein to bind heme, which was measured by CO difference and substrate-binding spectra. The D380 mutant protein had 3-fold reduction in peak heights in both spectra. This reduced heme binding resulted in 3-fold lower enzymatic activity.

Amino Acid Sequence↗
PubMed1999

Determination of anabolic steroids by gas chromatography/negative-ion chemical ionization mass spectrometry and gas chromatography/negative-ion chemical ionization tandem mass spectrometry with heptafluorobutyric anhydride derivatization.

A gas chromatography/mass spectrometry (GC/MS) method is described which uses negative ion chemical ionization (NCI) and tandem mass spectrometry (MS/MS) for the determination of eight anabolic steroids in human urine. Eight anabolic steroids were derivatized by heptafluorobutyric anhydride (HFBA), and were determined using GC/NCI-MS and GC/NCI-MS/MS. The linear correlation coefficients for calibration in NCI-MS/MS were in the range 0.9880-0.9988. This method of derivatization with HFBA for use with GC/NCI was useful in determinations of 19-norandrosterone, boldenone, 19-noretiocholanolone, 2-methylandrosterone, nandrolone, 1-methyleneandrosterone, 1-methylandrosterone, 4-dihydroboldenone and mesterolone. The detection limits of this procedure were 5-20 ppb at a signal-to-noise (S/N) ratio of 3.

Anabolic Agents↗
PubMed1999

Androgen imbalance in premenopausal women with benign breast disease and breast cancer.

OBJECTIVE: The alteration of steroid hormonal status in premenopausal breast disease (benign and malignant) were investigated by comparing the urinary profile of androgens and corticoids. METHODS: The urinary concentrations of 25 androgens and corticoids were quantitatively determined by a gas chromatographymass spectrometry system in patients with benign breast disease (35 cases, 20-54 years), breast cancer (34, 27-54), and healthy controls of similar age (25, 22-51). RESULTS: In premenopausal patients with breast cancer, a significantly lower rate of excretion of 11-deoxy-17-ketosteroids and their metabolites was found in comparison with normal females. These levels were also inversely associated with benign breast disease. No significant differences were found between the three groups for the concentration of 11-oxy-17-ketosteroids, 17-hydroxy-corticoids and their metabolites. The urinary ratio of adrenal androgen metabolites to cortisol metabolites [(11-DOKS & M)/11-OKS] declined in the order of normal female control (4.04 +/- 0.72; mean +/- SD), breast benign mass (2.29 +/- 0.42) and breast cancer (0.94 +/- 0.27). CONCLUSION: Our data suggest that the hormonal imbalance of androgen deficiency and/or corticoid sufficiency is closely associated with the benign and malignant conditions of premenopausal breast disease and the ratio of (11-DOKS & M)/11-OKS may be an effective discriminant factor of these groups.

Adrenal Cortex Hormones↗
PubMed1999

Comparison of fatty acid profiles in the serum of patients with prostate cancer and benign prostatic hyperplasia.

OBJECTIVE: The role of dietary fatty acids (FAs) in benign and malignant prostatic diseases was investigated by comparing the composition value of serum fatty acids in the normal controls, and patients with prostate cancer (PC) and benign prostatic hyperplasia (BPH). Also, to estimate a possible association between PC risk and PUFAs, omega-3, omega-6 and omega-3/omega-6 FA composition ratios were compared among these groups. METHODS: Serum samples were obtained from 24 BPH and 19 PC patients, and from 21 age-matched normal male subjects. The serum concentration of 21 fatty acids was determined using gas chromatography/mass spectrometry. RESULT: The proportional values of saturated fatty acids (SFAs) groups demonstrated no specific difference between the control subjects and the patients. In the polyunsaturated fatty acids (PUFAs), we found that the omega-3 PUFAs level was significantly decreased in patient with BPH and PC and that the omega-6 PUFAs level was increased in PC only. The ratio of omega-3/omega-6 PUFAs decreased in the following order of normal, BPH, and PC. CONCLUSION: It was proposed that the changed composition level of PUFAs including omega-3 and omega-6 PUFAs have certain relationship with both prostatic diseases. Therefore, the ratio of omega-3/omega-6 PUFAs also may have an important association with the benign and malignant status of prostatic disease.

Case-Control Studies↗
PubMed1999

Simultaneous GC-MS determination of nicotine and cotinine in plasma for the pharmacokinetic characterization of nicotine in rats.

A gas liquid chromatography/mass spectrometry assay method was developed for the simultaneous determination of nicotine and its major metabolite, cotinine, in rat plasma. Of particular interest was improving the low and variable extraction recovery for the parent drug and the metabolite. In addition, the feasibility of this assay method for pharmacokinetic studies of nicotine and cotinine after intravenous (i.v.), oral, and intraperitoneal (i.p.) administration of 1 mg kg(-1) of nicotine was tested. The low (30 and 48% for nicotine and cotinine, respectively) and variable (25 and 22% coefficient of variation for nicotine and cotinine, respectively) extraction recovery for nicotine and cotinine into dichloromethane was significantly improved by the addition of NaCl to the plasma. As a result, the recoveries for nicotine and cotinine were improved to 68 and 65%, respectively. The coefficient of variation was less than 10% in the 50-500 ng ml(-1) range and less than 16.58% at 10 ng ml(-1) for both nicotine and cotinine, indicating that the reproducibility of the assay was also improved by the extraction procedure. When injected intravenously at a dose of 1 mg kg(-1), the temporal profile of plasma concentration for nicotine followed a bi-exponential decline. Moment analysis revealed that pharmacokinetic parameters for nicotine (i.e. Cl, 46.30 ml min(-1) kg(-1); Vss, 2.77 1 kg(-1)) was similar to those reported in studies using 14C-nicotine. Absolute bioavailabilities of nicotine for i.p. and oral administration were 87.0 and 80.4%, respectively. The concentration of the metabolite increased up to 4 h to reach Cmax after i.p. and oral administrations and then declined slowly with time. These results indicate that this convenient analytical procedure is readily applicable to pharmacokinetic studies of nicotine and cotinine involving small laboratory animals with a sensitivity comparable with that reported for studies using 14C-nicotine.

Administration, Oral↗