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Biomedical subjects

Y H Hui

Publications and source records attributed to Y H Hui.

At least 19 recordsLinked to original sources
PubMed2001

New antimitotic agents with activity in multi-drug-resistant cell lines and in vivo efficacy in murine tumor models.

During a screen for compounds that could inhibit cell proliferation, a series of new tubulin-binding compounds was identified with the discovery of oxadiazoline 1 (A-105972). This compound showed good cytotoxic activity against non-multi-drug-resistant and multi-drug-resistant cancer cell lines, but its utility in vivo was limited by a short half-life. Medicinal chemistry efforts led to the discovery of indolyloxazoline 22g (A-259745), which maintained all of the in vitro activity seen with oxadiazoline 1, but also demonstrated a better pharmacokinetic profile, and dose-dependent in vivo activity. Over a 28 day study, indolyloxazoline 22g increased the life span of tumor-implanted mice by up to a factor of 3 upon oral dosing. This compound, and others of its structural class, may prove to be useful in the development of new chemotherapeutic agents to treat human cancers.

Animals↗
PubMed2000

Enhanced accuracy of needle placement in horizontal stereotactic core biopsy by a plastic slot.

Horizontal stereotactic core biopsy can be used in the investigation of clinically occult mammographic abnormalities especially when breast thickness is less than 3 cm. We designed a 6-mm plastic slot that can be inserted between the bushing and the biopsy gun to enhance the accuracy of needle placement within the lesion. With this device, the centre of the lesion can be targeted at the centre of the biopsy trough. We advocate the use of this piece of small, simple and inexpensive instrument in every case of horizontal stereotactic core biopsy.

Biopsy, Needle↗
PubMed1997

Development of a sensitive method for quantitation of ABT-089 in plasma using fluorescence labeling with 7-fluoro-4-nitrobenzo-2-oxa-1,3-diazole.

A high-performance liquid chromatography method for the quantitation of ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine] (I), a new structural type of cholinergic channel modulators (ChCM), is described in this paper using 7-fluoro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-F) as a fluorescent-labeling reagent. The method combined an optimized liquid-liquid extraction from plasma followed by pre-column derivatization to yield a fluorescence product. The selectivity, sensitivity, and reproducibility of this method were found to be excellent. This method was applied to the determination of ng/ml plasma and tissue levels of ABT-089 and similar compounds in biological samples.

4-Chloro-7-nitrobenzofurazan↗
PubMed1997

Analytical method development for the simultaneous quantitation of dexmedetomidine and three potential metabolites in plasma.

Dexmedetomidine, a novel alpha 2-adrenergic receptor agonist, is being developed as an anesthetic adjunct for perioperative use. An assay method has been developed for the sensitive quantitation of dexmedetomidine and three metabolites in plasma: MPV-1305, MPV-1306 and MPV-1709. The method involves solid-phase extraction (C18 cartridge) of dexmedetomidine and metabolites followed by a two-step derivatization. The first step utilized BF3-MeOH to simultaneously mask a primary alcohol in MPV-1305 and a carboxylic acid in MPV-1306. The second step applied PFB-Cl to derivatize the imidazole ring for sensitive detection of these compounds by GC-negative chemical ionization MS at pg/ml concentrations. MPV-1709 was not derivatized in the process and was detected by GC-positive chemical ionization MS. Optimization of extraction and derivatization is discussed. The method is suitable for quantitation of dexmedetomidine, MPV-1305, MPV-1306 and MPV-1709 over concentration ranges of 0.1, 40, 0.5-100, 0.5-100 and 1.0-500 ng/ml, respectively. The method showed excellent specificity, linearity and sensitivity and is useful for profiling the pharmacokinetic disposition of these compounds.

Adrenergic alpha-Agonists↗
PubMed1995

Efficacy of AZT therapy in reducing p24 antigen burden in a modified SCID mouse model of HIV infection.

A modified severe combined immunodeficient (SCID) mouse model of HIV infection which utilized multiple reconstitutions with human lymphocytes and a large inoculum of HIV was investigated. This mouse model yielded splenic HIV p24 antigen concentrations detectable by standard clinical means. The concentration of p24 exceeded 600 pg/g of spleen through 4 weeks postinfection. A 1-week course of AZT therapy initiated after infection produced a dose responsive reduction in p24 antigen burden. Up to a 95% reduction in p24 antigen burden was observed following AZT therapy at 50 mg/kg/day, while AZT therapy at 5 and 0.5 mg/kg/day produced 52 and 18% reductions. In vitro and pharmacokinetic evaluations correlated potency and tissue concentrations of AZT with treatment efficacy. Active HIV replication in the SCID mice was suggested by both the recovery of viable virus from SCID spleens, and by the efficacy of a brief course of AZT therapy. This SCID mouse model of HIV infection was more quantitative than previous mouse models that utilize PCR-based techniques for detection of HIV. The high HIV burden in this SCID mouse model allowed reductions in p24 concentration to be monitored in response to AZT therapy. A dose response to AZT therapy was demonstrated, even when the first dose was administered after infection. This result suggests greater sensitivity than in previous models in which pretreatment with AZT was required to produce a protective response. This SCID mouse model may be useful for determining efficacy of experimental HIV therapeutics prior to clinical use. An effective animal model could result in a reduction in cost and more rapid development of effective HIV therapeutics.

Animals↗
PubMed1994

10-, 12-, and 29-hydroxybullatacinones: new cytotoxic Annonaceous acetogenins from Annona bullata Rich (Annonaceae).

In our continuing activity-directed search for new antitumor compounds, using brine shrimp lethality (BST), mixtures of three additional pairs (1-6) of bis-THF ketolactone acetogenins were isolated from the ethanol extract of the bark of Annona bullata Rich. (Annonaceae). Compared with (2,4-cis and trans)-bullatacinone (7 and 8), these new compounds each have one more aliphatic OH group at a different position on the hydrocarbon chain, and, thus, were named (2,4-cis and trans)-10-hydroxybullatacinone (1 and 2), (2,4-cis and trans)-12-hydroxybullatacinone (3 and 4), and (2,4-cis and trans)-29-hydroxybullatacinone (5 and 6). These mixtures all showed potent activities in the brine shrimp lethality test (BST) and exhibited cytotoxicities comparable to those of adriamycin against human solid tumor cells in culture with selectivities exhibited especially toward the breast cancer cell line (MCF-7).

Acetylation↗
PubMed1994

Treatment of experimental Pneumocystis carinii infection by combination of clarithromycin and sulphamethoxazole.

The efficacy of clarithomycin and sulphamethoxazole for treatment of experimental Pneumocystis carinii infection was investigated. Rats were immunosuppressed with dexamethasone and inoculated intratracheally with 5 x 10(6) P. carinii cysts. After 2 weeks, the lung tissues were assayed for P. carinii cyst burden. The combination of clarithromycin and sulphamethoxazole caused a significantly greater reduction in cyst burden than either drug alone. Up to 50% of the rats treated with the combination of clarithromycin and sulphamethoxazole were negative for P. carinii cysts. Equivalent doses of the individual drugs given alone did not produce cures. The combination of clarithromycin and sulphamethoxazole was more than twice as effective as either drug alone. Clarithromycin combined with sulphamethoxazole in treatment of P. carinii infection could be especially useful since clarithromycin monotherapy provides safe and effective treatment against many other pathogens, including several that are associated with AIDS.

Animals↗
PubMed1993

Mode of action of bullatacin: a potent antitumor and pesticidal annonaceous acetogenin.

Bullatacin, a compound isolated from plants of the Annonaceae, and its analogues show in vivo potential as antitumor agents based on their efficacy in normal mice bearing L1210 murine leukemia and athymic mice bearing A2780 conventional ovarian cancer xenografts. These compounds also have interesting potential as insecticides and inhibit respiration in insect-derived Sf9 cells with high potency. Their toxicity in both cases probably arises from their strong inhibition of mitochondrial electron transport with a specific action at complex I.

Animals↗
PubMed1993

Biologically active acetogenins from stem bark of Asimina triloba.

In continuing our research with cytotoxic and pesticidal components from the stem bark of the North American paw paw, Asimina triloba, the novel cytotoxic monotetrahydrofuran Annonaceous acetogenins, cis- and trans-annonacin-A-one, cis- and trans-gigantetrocinone and cis-isoannonacin, in addition to the known compounds, trans-isoannonacin and squamolone, have been identified. Brine shrimp lethality testing was used to direct the fractionation. The structures were elucidated by spectral analysis and/or chemical synthesis. These acetogenins have potent cytotoxicities against the human tumour cell lines of A-549 (lung carcinoma), MCF-7 (breast carcinoma) and HT-29 (colon adenocarcinoma).

Animals↗
PubMed1992

Bullatencin, 4-deoxyasimicin, and the uvariamicins: additional bioactive Annonaceous acetogenins from Annona bullata Rich. (Annonaceae).

Additional bioactive Annonaceous acetogenins have been isolated from the EtOH extract of the bark of Annona bullata Rich. by bioactivity-directed fractionation using lethality to brine shrimp. These acetogenins include bullatencin, a new single tetrahydrofuran acetogenin having a double bond in the hydrocarbon chain; 4-deoxyasimicin, a new adjacent bis-tetrahydrofuran acetogenin; and the uvariamicins, an isomeric mixture of four single tetrahydrofuran acetogenins showed selective cytotoxicities for certain human solid tumor cell lines comparable to or better than adriamycin.

Animals↗
PubMed1990

16 alpha-hydroxy-(-)-kauranoic acid: a selectively cytotoxic diterpene from Annona bullata.

Using brine shrimp lethality to direct fractionation, extracts of the bark of Annona bullata Rich. (Annonaceae) have yielded 16 alpha-hydroxy-(-)-kauranoic acid as a bioactive plant constituent. This previously known diterpene showed significant (ED50 8.25 x 10(-2) micrograms/ml) and selective cytotoxicity against A-549 (lung) cells in our panel of human tumor cells.

Acetylation↗