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S H Chen

Publications and source records attributed to S H Chen.

At least 55 records · Page 3Linked to original sources
PubMed2001

Prodrugs of 3-amido bearing pseudomycin analogues: novel antifungal agents.

With the aim of identifying safer pseudomycin derivatives, we synthesized and evaluated a number of N-acyloxymethyl carbamate linked prodrugs of 3-amido pseudomycin analogues. To our satisfaction, all of the prodrug-amide combinations prepared exhibited good in vivo efficacy against murine Candidiasis. When evaluated in a dose elevation study, all of the newly synthesized combinations (e.g., 4A, 6A, 8A, and 8B) demonstrated improved toxicity profiles in comparison to their corresponding 3-amides as well as the parent pseudomycin B.

Amides↗
PubMed2001

Age-dependent dynamics of water in hydrated cement paste.

Self-dynamics of water molecules has been studied in hydrated tricalcium silicate as functions of temperature, aging, and in the presence of an additive. A dynamical model taking into account the existence of "immobile water" and "glassy water" has been used to analyze quasielastic neutron spectrometer spectra. We deduced the fraction of the immobile water (p), the stretch exponent (beta), and the average relaxation time (tau) of the glassy water. A quantitative picture for an aspect of the kinetics of the curing process and the structural relaxation parameters of the glassy water have been established.

Journal Article↗
PubMed2001

Characterization of stationary and nonstationary behavior in gyrotron oscillators.

The transition from the stationary state to a sequence of nonstationary states in the gyromonotron oscillator is experimentally characterized for the first time. We have also demonstrated the stationary operation of a gyrotron backward-wave oscillator at a beam current far in excess of the generally predicted nonstationary threshold. This difference in nonlinear behavior has been investigated and shown to be fundamental with a comparative analysis of the feedback mechanisms, energy deposition profiles, and field shaping processes involved in these two types of oscillations.

Journal Article↗
PubMed2001

Simultaneous monitoring of extracellular glucose, pyruvate, lactate and glutamate in gerbil cortex during focal cerebral ischemia by dual probe microdialysis.

The aim of this study was to monitor dynamic changes in energy-related metabolites in the cortex of gerbils subjected to cerebral ischemia by a dual probe microdialysis technique. Focal cerebral ischemia was produced in anesthetized gerbils by occlusion of the right common carotid artery and the right middle cerebral artery for 60 min. Two microdialysis probes were inserted into both sides of the cortex to simultaneously monitor extracellular glucose, lactate, pyruvate and glutamate. Dynamic and comparative changes in these analytes, on the ipsilateral and contralateral sides of the brain, were simultaneously monitored by liquid chromatography and a microdialysis analyzer. The present study demonstrated decreases in glucose and pyruvate, increases in lactate and glutamate on the ipsilateral side whereas all analytes remain constant on the contralateral side of cortex during cerebral ischemia. In vitro recovery of each microdialysis probe was performed to ensure the quality of experiments. The detection limits of pyruvate, glutamate, lactate and glucose were 0.2, 1.0, 2.0 and 20 microM, respectively. The intra- and inter-assay correlations were less than 5% in standard mixtures and pooled brain dialysates.

Animals↗
PubMed2001

Syntheses and antifungal activities of novel 3-amido bearing pseudomycin analogues.

As a result of our core SAR effort, we discovered a large number of 3-amido pseudomycin B (PSB) analogues (e.g., 4e LY448212 and 5b LY448731) that retain good in vitro and in vivo (IP) activities against Candida and Cryptococcus without inherent tail vein irritation. Several dimethylamino termini bearing 3-amides (e.g., 5b) also exhibited improved potency against Aspergillus in vitro. When evaluated in a two-week rat toxicology study, it was found that all animals receiving 4e (up to 75 mg/kg) were found to be normal. On the basis of these observations, we are convinced that it is possible to broaden the antifungal spectrum and improve the safety profile of pseudomycin analogues at the same time.

Amides↗
PubMed2001

Oxidative stress and c-Jun-amino-terminal kinase activation involved in apoptosis of primary astrocytes induced by disulfiram-Cu(2+) complex.

Disulfiram is frequently used in the treatment of alcoholism. In this study, we found that CuCl(2) (1-10 microM), but not other metal ions (Fe(2+), Zn(2+), Pb(2+)), markedly potentiated disulfiram-induced cytotoxicity by 440-fold in primary astrocytes. Thus, the molecular mechanisms of the cytotoxic effects induced by the disulfiram-Cu(2+) complex were explored. The changes in morphology (nuclear condensation and apoptotic body formation) and hypodiploidy of DNA suggested that the disulfiram-Cu(2+) complex induced an apoptotic process. Our studies of the death-signaling pathway reveal that decreased mitochondrial membrane potential, increased free radical production, and depletion of non-protein-thiols (glutathione) were involved. The disulfiram-Cu(2+) complex activated c-Jun-amino-terminal kinase (JNK) and caspase-3 followed by poly (ADP-ribose) polymerase degradation in a time-dependent manner. Moreover, the cellular Cu content was markedly increased and the copper chelator bathocuproine disulfonate abolished all of these cellular events, suggesting that Cu(2+) is essential for death signaling. The antioxidants N-acetylcysteine and vitamin C also inhibited the cytotoxic effect. Thus, we conclude that the disulfiram-Cu(2+) complex induces apoptosis and perhaps necrosis at a late stage mediated by oxidative stress followed by sequential activation of JNK, caspase-3 and poly (ADP-ribose) polymerase degradation. These findings imply that the axonal degeneration and neurotoxicity observed after the chronic administration of disulfiram are perhaps, at least in part, due to the cytotoxic effect of the disulfiram-Cu(2+) complex formed endogenously.

Animals↗
PubMed2001

Synthesis of glycosylated porphyrins as neutral ionophores for a berberine-sensitive electrode.

For preparing a berberine-sensitive electrode, 5,10,15,20-tetrakis[2-(2,3,4,6-tetraacetyl-beta-D-glucopyranosyl)-1-O- phenyl]porphyrin (T(o-glu)PPH2) was synthesized from the reaction of pyrrole with ortho-acetylglycosylated benzaldehyde by Lindsay's method. The electrode based on T(o-glu)PPH2 with an optimized membrane composition exhibits Nernstian response to berberine in the concentration range 2.4 x 10(-7)-5.0 x 10(-3) mol L-1, with a pH range from 3.9 to 10.2, and a fast response time of 30 s. The electrode shows fair selectivity towards berberine with respect to common co-existing species. T(o-glu)PPH2 shows better potentiometric response characteristics comparing to chloro[5,10,15,20-tetrakis[2-(2,3,4,6-tetraacetyl-beta-D- glucopyranosyl)-1-O-phenyl]-porphinato]-manganese (MnT(o-glu)PPCl) and better selectivity towards berberine than tetraphenylporphyrin (TPPH2). The effect of the composition of the electrode membrane has been studied and the experimental conditions optimized. The contents of berberine in pharmaceutical tablets were determined by direct potentiometry and the results agreed with values obtained by the pharmacopoeia method.

Berberine↗
PubMed2001

8-Amido-Bearing pseudomycin B (PSB) analogue: novel antifungal agents.

During the course of a structure-activity relationship (SAR) study on novel depsinonapeptide pseudomycin B, we synthesized a total of 12 8-amidopseudomycin analogues via standard two-step sequence from either ZPSB 2 or AllocPSB 3. A number of these amides exhibited good in vitro antifungal activities.

Animals↗
PubMed2001

Collective dynamics in fully hydrated phospholipid bilayers studied by inelastic x-ray scattering.

The short wavelength density fluctuation of DLPC (dilaurylphosphatidylcholine) bilayers close to full hydration has been studied by the inelastic x-ray scattering technique below and above the main transition temperature. The analysis based on a generalized three effective eigenmode theory allows us to construct the dispersion relation of the high frequency sound mode for the first time. The marked softening of the excitation near k = 14 nm(-1), corresponding to the lipid chain-chain correlation peak in the structure factor, in the L(alpha) phase implies prevalent occurrences of short-wavelength in-plane motions of lipid chains that might be of importance for transportation of small molecules across membranes.

Lipid Bilayers↗
PubMed2001

Clipped random wave analysis of anisometric lamellar microemulsions.

Small-angle neutron scattering experiments were performed on C10E4-D2O-octane (where C10E4 is tetraethylene glycol monodecyl ether) anisometric microemulsions in the lamellar phase at a constant surfactant volume fraction of 20% and at the hydrophile-lipophile balance temperature of 22.5 degrees C. The results were analyzed using a clipped random wave model with a specific spectral distribution function developed by us previously. This enabled us to generate three-dimensional morphologies of the microemulsions, which showed clearly that in sufficiently anisometric microemulsions the oil-water interface was no longer connected. At large anisometry isolated regions of oil or water were found, and the transition from a bicontinuous structure at isometry to these isolated micelles far from isometry goes through an intermediate cylindrical morphology when the oil-to-water or water-to-oil ratio is around 4 to 1. We further computed the joint distribution function of the mean curvature H and Gaussian curvature K of the entire oil-water interface for each anisometric microemulsion. In particular, we show the distribution of , , and - (2) for different isolated regions within an oil-rich microemulsion at an oil-to-water ratio of 85% to 15%. These distributions allowed us to prove that the isolated regions formed in highly anisometric microemulsions were small and had spherical topology.

Journal Article↗
PubMed2001

Parathyroidectomy can improve bone mineral density in patients with symptomatic secondary hyperparathyroidism.

HYPOTHESIS: The recovery of osteoporosis or bone mineral density (BMD) after parathyroidectomy and autotransplantation can be improved in patients with symptomatic secondary hyperparathyroidism. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Forty-five patients with symptomatic secondary hyperparathyroidism who underwent total parathyroidectomy and autotransplantation were included. They were divided into an osteoporotic group (n = 20) and a nonosteoporotic group (n = 25) according to preoperative T scores less than -2.5 at either the lumbar spine (L1-L4) or the femoral neck (FN). INTERVENTIONS: Serum levels of calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone were checked before surgery and 1 day, 1 week, and 3 months after surgery. The BMDs of the FN and L1-L4 were measured using dual-energy x-ray absorptiometry before surgery and 6 months after surgery. RESULTS: Patients with osteoporosis were older (mean +/- SD, 50.2 +/- 14.0 years) than those without osteoporosis (42.7 +/- 9.1 years) (P =.04). Except for bone fractures found in 2 women in the osteoporotic group, there were no significant differences between the 2 groups in sex, clinical manifestations, duration of dialysis, weight of removed parathyroid tissue, and types of dialysis. Also, serum levels of calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone were similar in both groups. Both 1 day and 1 week after total parathyroidectomy and autotransplantation, serum levels of calcium and intact parathyroid hormone decreased rapidly and then gradually increased 3 months later; however, serum levels of alkaline phosphatase increased rapidly and then gradually decreased 3 months later. Six months after parathyroidectomy, BMD, T score, and Z score at L1-L4 and the FN increased significantly (P<.001). The increment was much better in the osteoporotic group than in the nonosteoporotic group (P<.001). Also, osteopenia or osteoporosis improved significantly after parathyroidectomy at both L1-L4 and the FN (P<.001 for both). CONCLUSION: Parathyroidectomy and autotransplantation can improve BMD of symptomatic secondary hyperparathyroidism at L1-L4 and the FN.

Absorptiometry, Photon↗
PubMed2001

Plastic microchip electrophoresis for genetic screening: the analysis of polymerase chain reactions products of fragile X (CGG)n alleles.

Clinical screening of abnormal chromosomes associated with fragile X syndrome (FXS) demands a high-throughput method including DNA sizing and detection of the amplified products. This study is to explore the use of polymer microchip electrophoresis for the analysis of polymerase chain reaction (PCR) products of fragile X (CGG)n alleles to facilitate a fast exclusion test of FXS. The sequences flanking the CGG-repeat of FMR1 gene was amplified by betaine-PCR and the amplified products were desalted and then analyzed by microchips which were fabricated on poly(methyl methacrylate) (PMMA) substrate. The PCR bands with more than six CGG-repeats in difference could be clearly distinguished in less than 3 min by microchip electrophoresis with a separation length of 6 cm. It was found that the signal was greatly enhanced with the use of both covalent (Cy5) and intercalating dye (TORRO-3), which has never been demonstrated before. We tested the method by reanalysis of twelve samples from males and six samples from females. For female samples with less than six repeat differences, Southern blotting method was performed to confirm or exclude the findings from microchips. It was found that the test results from all male and female samples show a 100% correlation between the microchip electrophoresis and the existing methods.

Electrophoresis, Capillary↗
PubMed2001

Head-column field-amplified sample stacking in capillary electrophoresis for the determination of cimetidine, famotidine, nizatidine, and ranitidine-HCl in plasma.

In this study, low concentrations of histamine2-receptor (H2-)antagonists were effected across a water plug, with separation taking place in a binary buffer comprising ethylene glycol and NaH2PO4 (pH 5.0), and detection at 214 nm. Liquid-liquid extraction with ethyl acetate- isopropanol is shown to provide extracts that are sufficiently clean. The calibration curves were linear over a concentration range of 0.1-2.00 microg/mL cimetidine, 0.2-5.0 microg/mL ranitidine-HCl, 0.3-5.0 microg/mL nizatidine, and 0.1-3.0 microg/mL famotidine. Mean recoveries were > 82%, while the intra- and interday relative standard deviations (RSDs) and relative errors (REs) were all < 13%. The method is sensitive with a detection limit of 3 ng/mL cimetidine, 30 ng/mL ranitidine HCl, 50 ng/mL nizatidine and 10 ng/mL famotidine (S/N = 3, electric-driven injection 90 s). This newly developed capillary electrophoresis (CE) method was applied for the determination of analytes extracted from plasma taken from a volunteer dosing a cimetidine, ranitidine, and nizatidine tablet simultaneously. These three H2-antagonists can be detected in real samples by this method, excluding the low dosing of famotidine tablet.

Buffers↗
PubMed2001

Simultaneous determination of cimetidine, famotidine, nizatidine, and ranitidine in tablets by capillary zone electrophoresis.

A simple capillary zone electrophoresis (CZE) method is described for the simultaneous determination of cimetidine (CIM), famotidine (FAM), nizatidine (NIZ), and ranitidine (RAN). The analysis of these drugs was performed in a 100 mM phosphate buffer, pH 3.5. Several parameters were studied, including wavelength for detection, concentration and pH of phosphate buffer, and separation voltage. The quantitative ranges were 100-1,000 microM for each analyte. The intra- and interday relative standard deviations (n = 5) were all less than 4%. The detection limits were found to be about 10 microM for CIM, 20 microM for RAN, 20 microM for NIZ, and 10 microM for FAM (S/N = 3, injection 1 s) at 214 nm. All recoveries were greater than 92%. Applications of the method to the assay of these drugs in tablets proved to be feasible.

Anti-Ulcer Agents↗
PubMed2001

A disposable poly(methylmethacrylate)-based microfluidic module for protein identification by nanoelectrospray ionization-tandem mass spectrometry.

The design, fabrication, and analytical use of a poly(methylmethacrylate) (PMMA)-based microfluidic module for nanoelectrospray ionization-tandem mass spectrometry (nano-ESI-MS/MS) were described. The microfluidic module can be mass-produced at low costs and used as a disposable device to generate nano-ESI-MS/MS signals for protein identification from low amounts of protein samples. Compared with commercially available nanospray capillary tips, the module gave comparable signal quality and also offered advantages in convenience and easiness of operation, permitting repeated usage, and disposability.

Animals↗
PubMed2001

Recent advances in pharmacokinetic applications of capillary electrophoresis.

This article reviews recent capillary electrophoresis (CE)-based assays which were published for pharmacokinetic studies. Both the advantages and disadvantages of these CE-based assays are discussed based on their feasibility and the significance towards the better understanding of pharmacokinetics. In addition, as a future outlook, novel assays such as immunoaffinity CE and chip-based CE for analyzing drugs in biological fluids are summarized in view of their potential for pharmacokinetic applications.

Electrophoresis↗
PubMed2001

Inhibition of melanoma growth and metastasis by combination with (-)-epigallocatechin-3-gallate and dacarbazine in mice.

(-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, was shown to have cancer chemopreventive activity. In this study, we examined the antimetastatic effects of EGCG or the combination of EGCG and dacarbazine on B16-F3m melanoma cells in vitro and in vivo. First, the antimetastatic potentials of five green tea catechins were examined by soft agar colony formation assay, and the results show that EGCG was more effective than the other catechins in inhibiting soft agar colony formation. Second, EGCG dose-dependently inhibited B16-F3m cell migration and invasion by in vitro Transwell assay. Third, EGCG significantly inhibited the spread of B16-F3m cells on fibronectin, laminin, collagen, and Matrigel in a dose-dependent manner. In addition, EGCG significantly inhibited the tyrosine phosphorylation of focal adhesion kinase (FAK) and the activity of matrix metalloproteinase-9 (MMP-9). In animal experiments, EGCG alone reduced lung metastases in mice bearing B16-F3m melanomas. However, a combination of EGCG and dacarbazine was more effective than EGCG alone in reducing the number of pulmonary metastases and primary tumor growths, and increased the survival rate of melanoma-bearing mice. These results demonstrate that combination treatment with EGCG and dacarbazine strongly inhibits melanoma growth and metastasis, and the action mechanisms of EGCG are associated with the inhibition of cell spreading, cell-extracellular matrix and cell-cell interactions, MMP-9 and FAK activities.

Animals↗