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Biomedical subjects

S Y Yeung

Publications and source records attributed to S Y Yeung.

10 recordsLinked to original sources

Scavenging property of three cresol isomers against H2O2, hypochlorite, superoxide and hydroxyl radicals.

Formocresol has long been used for pulpotomy of primary teeth and as an intracanal medicament. Little is known, however, about the pharmacological effect of tricresols. This study showed that three cresol isomers, o-cresol, m-cresol and p-cresol, are H2O2 scavengers with a 50% inhibitory concentration (IC50) of 502, 6.7 and 10.16 microM, respectively. o-, m- and p-cresol were also shown to be effective scavengers of superoxide radicals generated by xanthine/xanthine oxidase with an IC50 of 282, 153 and > 4000 microM, respectively, as analyzed by luminometer. o-, m- and p-cresol showed protective effects on the DNA breaks generated by H2O2/FeCl2 and FeCl3/ascorbate/H2O2 systems at concentrations ranging from 70 microM to 1.43 mM, o-, m- and p-cresol also showed differential protective effects against DNA breaks induced by 0.17% NaOCl with 100% inhibitory concentration (IC100) of about 10, 1 and 10 mM, respectively. In addition, reaction with 3% H2O2 and 0.17% NaOCl completely prevented NaOCl-induced DNA breaks. The results indicate that the three cresol isomers are effective ROS scavengers and may prevent ROS induced damage when used as pulpotomy agents or as intracanal medicaments. Owing to the difference in the position of the functional hydroxyl group in the three cresol isomers, m-cresol is the most effective ROS scavenger. Concomitant use of H2O2 for root canal irrigation may diminish both the tissue dissolving capacity of NaOCl and NaOCl-induced DNA damage.

Acridines↗

Inhibition of delayed rectifier K+ conductance in cultured rat cerebellar granule neurons by activation of calcium-permeable AMPA receptors.

Activation of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors in cerebellar granule cells during perforated-patch whole-cell recordings activated an inward current at negative voltages which was followed, after a delay, by the inhibition of an outward potassium current at voltages positive to -20 mV. The activated inward current was inwardly rectifying suggesting that the AMPA receptors were Ca2+-permeable. This was confirmed by direct measurements of intracellular calcium where Ca2+ rises were seen following AMPA receptor activation in Na+-free external solution. Ca2+ rises were equally large in the presence of 100 microM Cd2+ to block voltage-gated Ca2+ channels. Specific voltage-protocols, allowing selective activation of the delayed rectifier potassium current (KV) and the transient A current (KA), showed that kainate inhibited KV, but not to any great extent KA. The inhibition of KV was blocked by the AMPA receptor antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) and was no longer observed when the KV current was abolished with high concentrations of Ba2+. The responses to kainate were not altered by pre-treating the cells with pertussis toxin, suggesting that the AMPA receptor stimulation of the G-protein Gi cannot account for the effects observed. Replacing extracellular Na+ with choline did not alter the inhibition of KV by kainate, however, removing extracellular Ca2+ reduced the kainate response. The inhibition of KV by kainate was unaffected by the presence of 100 microM Cd2+. The guanylyl cyclase inhibitor, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), did not alter kainate inhibition of KV. It is concluded that ion influx (particularly Ca2+ ions) through AMPA receptor channels following receptor activation leads to an inhibition of KV currents in cerebellar granule neurons.

Animals↗

Characterization of a functional AT1A angiotensin receptor in pancreatoma AR4-2J cells.

Functional angiotensin receptors were characterized in the rat pancreatic acinar cell line AR4-2J. Angiotensin II stimulated a dose-dependent release of amylase and production of inositol phosphates. Results of high-performance liquid chromatography separation of inositol phosphates indicated that angiotensin stimulated the rapid accumulation of inositol 1,3,4-trisphosphate. Angiotensin II and angiotensin III were at least an order of magnitude more potent than angiotensin I in the stimulation of amylase release. The angiotensin II-stimulated amylase release was blocked by losartan, a selective AT1 angiotensin antagonist. The selective AT2 angiotensin receptor ligands CGP42112 did not alter angiotensin II-stimulated amylase released. However, CGP42112 stimulated amylase release at micromolar concentrations with a potency similar to angiotensin I. Analysis of mRNA expression by reverse transcription polymerase chain reaction suggested that AT1A was the predominant type-I angiotensin receptor expressed in the AR4-2J cells.

Amylases↗

Inhibition of neuronal KV potassium currents by the antidepressant drug, fluoxetine.

1. The effect of the antidepressant drug, fluoxetine on neuronal delayed rectifier (KV) potassium (K) currents was investigated using perforated-patch whole-cell electrophysiological recording methods. 2. Fluoxetine was an effective inhibitor of KV currents in cerebellar granule neurons (CGNs) and also inhibited recombinant KV1.1 channels expressed in Chinese hamster ovary (CHO) cells. 3. Fluoxetine had an IC50 of 11 microM in CGNs but was slightly less potent on KV1.1 channels (IC50=55 microM). Interestingly, fluoxetine was a much more potent inhibitor of KV1.1 expressed in mammalian cells than has been found previously for the same homomeric channel expressed in Xenopus oocytes. 4. At concentrations that produced around 50% block, the shape of the KV currents in the presence of fluoxetine was simply scaled down when compared to control currents. 5. The effect of fluoxetine on KV currents in CGNs was neither voltage-dependent nor dependent on the channels being in their open state. Both of these observations suggest that fluoxetine does not act as a simple open channel blocking agent. 6. It is concluded that block of KV currents in mammalian neurons can occur at therapeutic levels of fluoxetine. This could lead to an increase in neuronal excitability and this effect may contribute to the therapeutic antidepressant action of fluoxetine.

Animals↗

Immunohistochemical localization of type-II (AT2) angiotensin receptors with a polyclonal antibody against a peptide from the C-terminal tail.

A polyclonal antibody has been prepared against a synthetic peptide derived from the C-terminal tail of the cloned rat AT2 angiotensin receptor, corresponding to amino acid residue 341-351. The antibody was of high titer and displayed monospecific activity toward the synthetic peptide in the ELISA assay. Western blot analysis indicated that the antiserum recognised only a single protein band with a mean apparent molecular mass of 75.4 kDa in the rat adrenals. Immunohistochemical studies with affinity purified antibody localised immunoreactive AT2 angiotensin receptor in medulla cells of the adrenals. Immunoreactivity was also observed in pyramidal tract, but no specific immunoreactivity can be detected in regions of rat brain that are known to express AT2 angiotensin receptors, including inferior olive, locus coeruleus and cerebellum.

Adrenal Glands↗

Induction of antigen-reactive and IL-2 receptor bearing cells following oral immunization in humans.

A human model of oral immunization using two forms of HI antigen preparation was studied. Oral immunization with killed HI (monobacterial) or HI in a polybacterial mix (polybacterial) induced an enhanced antigen-driven proliferative response in circulating PBL of normal subjects as well as an increase in the precursor frequency of HI antigen-specific cells using limiting dilution analysis. However, the proliferative response was better maintained at a high level in subjects after completion of immunization with the polybacterial vaccine, whereas the response was small and transient following oral immunization with the monobacterial vaccine. Clonal analysis of the proliferative response demonstrated that the precursor frequency of HI antigen-specific cells in the circulating pool was not expanded to account for the differences, despite repeated ingestion of the vaccine. An analysis of PBL following oral immunization using anti-TAC monoclonal antibody revealed an increase in the number of IL-2 receptor-bearing cells in subjects orally immunized with the polybacterial vaccine, with maximal numbers occurring at day 62 when the number of precursors fell but the proliferative response remained high. This suggests that the enhanced and sustained proliferation in bulk cultures is due in part to a contribution to the overall proliferation by in vivo polyclonally-activated IL-2 receptor positive cells which proliferate in the presence of IL-2. Taken together, the results obtained are consistent with the concept that 'restricted' cell activation may be important in the mechanism of selective protection found following oral immunization with monobacterial HI vaccine.

Administration, Oral↗

Applications of purification reactions for minimizing reaction-generated enzyme poisoning.

A mathematical model has been employed to examine the interplay of reaction and mass transfer in immobilized enzyme systems involving reaction-generated enzyme poisions. Deactivation rates can be significantly reduced in some cases by catalyzing a purification reaction in which the poison is transformed into an innocuous substance. This conclusion in illustrated experimentally for reaction-generated H2O2 in a continuous-flow stirred slurry reactor containing glucose oxidase immobilized on activated carbon.

Enzymes, Immobilized↗