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Biomedical subjects

T H Chiu

Publications and source records attributed to T H Chiu.

At least 55 records · Page 3Linked to original sources
PubMed1995

Inhibition of locus coeruleus neurons by serotonin at high doses.

Using brain slice and intracellular recording techniques, this study was conducted in the attempt to evaluate whether serotonin (5-HT) is able to directly influence neuronal activities of the locus coeruleus (LC). LC neurons in the brain slice preparation show spontaneous firing in the absence of synaptic input; neurons in this work had firing rates ranging from 0.18-3.6 Hz (mean = 1.18 +/- 0.26 Hz). Concentrations of 5-HT from 30 to 300 microM were used, which reversibly decreased the spontaneous firing rate in 30 out of 36 LC neurons tested. In testing those cells with more than one concentration, the effect was dose-dependent. For LC neurons which showed complete block of firing by 5-HT (300 microM), the latency to block was found to be directly related to the firing rate. In addition to the inhibition of spontaneous firing, 5-HT (300 microM) also caused a 0-5 mV (mean = 3.2 mV, n = 10) hyperpolarization associated with a 2.2-21% (mean = 11.5%, n = 10) decrease in input resistance. Lower concentrations of 5-HT (30-100 microM) did not produce any significant change in membrane potential or input resistance in neurons of the LC. The 5-HT receptor antagonist methysergide (10 microM) was tested in 6 cells. Methysergide antagonized the 5-HT-induced inhibition of firing, hyperpolarization and reduction in input resistance. We concluded that 5-HT has inhibitory actions at high doses when applied to LC neurons in the brain slice preparation. 5-HT's inhibitory effects on LC neurons appear to be mediated by 5-HT receptors since they are antagonized by methysergide.

Animals↗
PubMed1994

c-fos antisense attenuates Fos expression in rat central neurons induced by hemorrhage.

Hemorrhage caused by withdrawing 3-4 cm3 of blood from adult rats over a period of 1-2 h induced the expression of Fos proteins, which were detected by immunocytochemical methods in neurons of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, area postrema, nucleus of the solitary tract (NTS), ventrolateral medulla (VLM) and in intermediolateral cell column (IML) of the spinal cord. Daily intraventricular (i.c.v.) injections of c-fos antisense (50 nmol 5 microliters -1) for 2 days prior to hemorrhage markedly attenuated the extent and intensity of Fos-immunoreactivity (FOS-IR) compared with that of rats injected with c-fos sense in the areas mentioned above. The results indicate the effectiveness of i.c.v. administration of c-fos antisense in blocking Fos expression in central neurons following hemorrhage.

Animals↗
PubMed1994

Hydroxyl radical generation and nitric oxide synthase activity in Fisher 344 x brown-Norway F1 rat brain.

Hydroxyl radical production in the cerebral cortex, striatum and hippocampus of young (6 months), middle-aged (15 months) and old (28 months) Fisher 344 x Brown-Norway F1 rats was quantitated by measuring the salicylate hydroxyl radical-trapping product, 2,5-dihydroxybenzoic acid. The levels of hydroxyl radical between different age groups in each region examined were not statistically different. In all regions, with the exception of hippocampus from old rats which had a lower content of hydroxyl radical, the levels of hydroxyl radical were higher for middle-aged and old rats than young ones. There was no regional difference in the production of hydroxyl radicals, except that the level was significantly higher in striatum than in cortex for 15-month-old rats. The cerebral cortical nitric oxide synthase activities were similar in the three age groups studied.

Aging↗
PubMed1994

Lipoteichoic acid from Streptococcus sanguis is a natural glucosyl acceptor for glucosyltransferases.

The synthesis of methanol insoluble-[14C]labeled-polymers from [14C]sucrose by S. mutans glucosyltransferases was stimulated up to four-fold by the presence of highly purified, lipoteichoic acid (LTA) from S. sanguis. Gel filtration chromatography (Sepharose 4B) and ion exchange chromatography (DEAE-Bio-Gel A) of the [14C]labeled-polymers formed in the presence of [3H]glycerol-labeled-LTA showed that high molecular weight, negatively charged [14C]labeled-[3H]glycerol-labeled-LTA complexes were being formed. The [14C]component was identified as glucose by acid hydrolysis and paper chromatography. A similar high molecular weight, negatively charged [14C]glucosyl-[3H]glycerol-labeled-polymer was extracted from S. mutans cells grown in the presence of [3H]glycerol and [14C]sucrose, suggesting that LTA is a glucosyl-acceptor for glucosyltransferases in vivo as well as in vitro.

Chromatography, Gel↗
PubMed1994

Decreased expression of gamma-aminobutyric acid type A/benzodiazepine receptor beta subunit mRNAs in brain of flurazepam-tolerant rats.

The expression of GABAA/benzodiazepine beta subunit mRNAs was studied in cerebral cortex, hippocampus, and cerebellum of flurazepam-treated rats. Immediately following 4 wk of treatment, beta 2 and beta 3 subunit mRNAs were significantly reduced in cerebellum and hippocampus, whereas only beta 2 was decreased in cortex. These decreases had largely reversed 48 h following flurazepam treatment. After 2 wk of treatment, both beta 2 and beta 3 mRNAs were reduced in cerebellum, and beta 3 mRNA was reduced in hippocampus, but neither was changed in cortex. Four hours after an acute flurazepam treatment, the only change was a decrease in beta 3 mRNA in hippocampus. These results indicate that the expression of GABAA receptor beta subunit mRNAs in different brain regions is differentially regulated during chronic flurazepam treatment, and some changes occur within hours after a single large dose.

Animals↗
PubMed1994

Subunit- and brain region-specific reduction of GABAA receptor subunit mRNAs during chronic treatment of rats with diazepam.

The mRNA levels for several GABAA receptor subunits were measured by Northern blot analysis. Rats were treated for 3 wk by continuous release of diazepam (DZP) from subcutaneous reservoirs, and then sacrificed immediately or 48 h after removing the reservoirs. Poly(A)+ RNAs, isolated from cerebral cortex, cerebellum, and hippocampus, were hybridized with oligonucleotide probes for GABAA receptor subunits and a cDNA probe for beta-actin. Subunit mRNAs were expressed relative to the corresponding beta-actin mRNA. DZP treatment decreased the alpha 1 subunit mRNA level 40% in hippocampus, but it was not changed in cortex or cerebellum. The alpha 5 subunit mRNA level was decreased in cerebral cortex (28%) and hippocampus (15%). The gamma 2 subunit mRNA level was decreased (40%) only in cortex. DZP treatment did not affect alpha 2, alpha 3, alpha 4, beta 2, or beta 3 subunit mRNA levels. Decreases in mRNA levels had reversed within 48 h after stopping chronic treatment. Acute DZP did not change alpha 1, alpha 5, or gamma 2 subunit mRNA levels. The decreases in GABAA receptor subunit mRNA levels were specific to subunit and brain region. These results, coupled with those after chronic flurazepam treatment, also indicated that the effects on GABAA receptor subunit mRNA levels are specific to the benzodiazepine (BZ) used for chronic treatment.

Animals↗
PubMed1994

Actions of a long-acting somatostatin analog SMS201-995 (sandostatin) on rat locus coeruleus neurons.

The actions of sandostatin involving rat locus coeruleus (LC) neurons were examined using an intracellular recording in a brain slice preparation. Bath application of sandostatin (5-100nM) reversibly decreased the firing rate of all neurons tested in a dose-dependent manner. Sandostatin was 9.5 times more potent than somatostatin in light of an inhibition of the spontaneous firing rate. In addition to the inhibition of spontaneous firing, larger concentrations of sandostatin (30-100nM) also hyperpolarized the neurons of the locus coeruleus and simultaneously caused a reduction in input resistance. At the highest concentration (100nM) applied, sandostatin produced complete inhibition of firing of all neurons tested (n = 49); the inhibition was associated with a 11.6mV hyperpolarization (range 2.2-26.4 mV, n = 49) and a 21.8% reduction in input resistance (range 2.6-55.2%, n = 39). The voltage-current relationship of the resting cell revealed an inward-going rectification that became enhanced after the perfusion of sandostatin (100nM) for 5 min. The reversal potential for the sandostatin-induced hyperpolarization was -111 +/- 1 mV (n = 10), which is approximately the potassium equilibrium potential. This hyperpolarization was blocked by both caesium chloride and barium chloride. Our results also showed that sandostatin displayed an antagonistic action on mu opiate receptors. Both the somatostatin-agonistic and opiate-antagonistic activities of sandostatin were conclusively found to be stronger than those of somatostatin; in addition, the inhibitory actions of sandostatin on LC neurons were due to an opening of the inward-going rectification potassium channels.

Animals↗
PubMed1994

Zinc inhibition of GABA-stimulated Cl- influx in rat brain regions is unaffected by acute or chronic benzodiazepine.

Zinc modulation of GABAA receptor function was studied using GABA-stimulated 36Cl- influx into microsacs prepared from rat cerebral cortex, cerebellum and hippocampus. Zinc (10-100 microM) did not affect the basal influx, but significantly inhibited GABA-stimulated 36Cl- influx. The inhibition appeared to be noncompetitive. Zinc produced differing degrees of inhibition of GABA-stimulated 36Cl- influx in different brain regions. The order of sensitivity to zinc inhibition of GABA-stimulated 36Cl- influx was hippocampus > cerebral cortex > cerebellum. These regional differences may reflect the structural heterogeneity of GABAA receptors among brain areas. Zinc inhibition was not affected by the short-term addition of three benzodiazepines, diazepam, bretazenil and triazolam. The effect of diazepam and bretazenil to potentiate GABA-stimulated 36Cl- influx was not affected by zinc, but the effect of triazolam was decreased by zinc. In brain tissue prepared from flurazepam-treated rats, there was no difference compared with controls in zinc inhibition of GABA-stimulated 36Cl- influx. The results indicate that the effects of zinc on the GABAA receptor are largely independent of drugs acting on the benzodiazepine binding site.

Animals↗
PubMed1994

Differential regulation of superoxide dismutase in copper-deficient rat organs.

The effects of dietary copper deprivation on the activities, immunoreactive protein concentrations, and mRNA abundance of copper/zinc- and manganese-superoxide dismutase (Cu/Zn- and Mn-SOD) were examined in liver, heart, and brain of weanling rats fed a Cu-deficient diet for 4 weeks. Hepatic Cu/Zn-SOD activity, enzyme content, and mRNA abundance were significantly reduced, and, conversely, the activity, protein, and mRNA levels of Mn-SOD were significantly elevated in Cu-deficient rats. In Cu-deficient heart, the activity and protein content for Cu/Zn-SOD were reduced, whereas those for Mn-SOD were increased; the levels of mRNAs for these two enzymes was unaffected. Dietary Cu deficiency was without effect on the activities, enzyme contents, and mRNA abundance of brain Cu/Zn- and Mn-SOD. These results indicate that SODs from liver, heart, and brain exhibit differential sensitivities to dietary Cu deprivation, and that different mechanisms (transcriptional, posttranscriptional, or posttranslational) may be involved in their regulation.

Animals↗
PubMed1994

Growth discordancy, birth weight, and neonatal adverse events in third trimester twin gestations.

In order to understand the effects of intrauterine growth discordancy (15% or more birth weight difference), birth weight, and gestational age on the neonatal adverse events (including 1- or 5-min Apgar scores < 7, neonatal death, ICU admission, respiratory distress, hypoglycemia, hypocalcemia, perinatal infection, blood transfusion, and hyperbilirubinemia) in third trimester twin gestations, 279 consecutive twin pairs delivered from January 1986 to December 1991 were studied. Univariate analyses showed discordant twins were smaller than concordant twins in gestational age by 1.4 weeks (35.74 and 37.14 weeks respectively). When birth weight was compared, that of smaller (one with lower birth weight in a pair) discordant twins (1,951 g) was significantly lower than that of smaller concordant twins (2,423 g), while larger (one with higher birth weight in a pair) discordant twins (2,556 g) and concordant twins (2,594 g) showed no significant difference. Univariate analysis indicated there was a tendency for adverse events to occur in discordant twins, especially in the smaller twin. Through logistic regression analysis, it was found that birth weight and gestational age, but not discordancy, are the predictors of the occurrence of adverse events. A smaller twin weighing no more than 2,000 g has a 10 times greater risk to develop an adverse event as compared to a twin with a birth weight over 2,000 g and a similar gestational age; while a twin with a gestational age of less than 34 weeks has a 5 times greater risk than one 34 weeks or over with a similar birth weight.

Apgar Score↗
PubMed1994

alpha-Fetoprotein levels of paired samples between the amniotic fluid and maternal serum from 16 to 18 weeks' gestation in Chinese women.

To assess the relationship between alpha-fetoprotein (AFP) concentrations of amniotic fluid and maternal serum from 16 to 18 weeks' gestation, 890 paired samples of maternal serum and amniotic fluid were collected from women with normal singleton pregnancies. The gestational age was determined by ultrasonographic dating before amniocentesis, and the AFP measurements were performed by a single reference laboratory. There was a significant rise in the maternal serum AFP (MSAFP) concentration from 16 to 18 weeks' gestation. Amniotic fluid AFP concentrations significantly declined from 16 to 18 weeks' gestation. This study failed to demonstrate any statistical relationship between the AFP concentration of maternal serum and amniotic fluid (r = 0.031). This finding indicates that amniotic fluid AFP levels cannot be predicted by MSAFP levels between 16 and 18 weeks' gestation. Simple diffusion may not be the only mechanism for the transfer of AFP through the fetal membrane to maternal circulation.

Amniotic Fluid↗
PubMed1994

Maternal serum alpha-fetoprotein levels between 13 and 24 weeks' gestation.

Maternal serum alpha-fetoprotein (MSAFP) screening has been widely used and proven valuable in the prediction of a variety of fetal disorders. Any laboratory intending to provide MSAFP screening needs to establish its own reference data. In order to establish a normal MSAFP median value at our own laboratory, 5256 samples of MSAFP were collected from uncomplicated, singleton pregnant women between 13 and 24 weeks' gestation. The MSAFP median levels steadily rise with advancing gestation about 16% per gestational week in average. There were 0.17% and 4.4% of the pregnancies with serum AFP levels less than 0.25 multiple of the median (MoM) and 0.5 MoM respectively, and 4.22% and 1.66% with serum levels above 2.0 MoM and 2.5 MoM. Accurate and satisfactory interpretation of MSAFP screening should be emphasized in the establishment of a well-developed normal median value.

Female↗
PubMed1994

Effects of somatostatin-28 on rat locus coeruleus neurons.

The effects of somatostatin-28 (SS-28) on rat locus coeruleus (LC) neurons were investigated with techniques of brain slice and intracellular recording. SS-28 was applied by micropressure ejection through a micropipette. SS-28 (500 microM, 10 or 20 psi, 1 msec - 5 sec) reversibly decreased the firing rate of all neurons of the locus coeruleus tested. In addition to inhibition of spontaneous firing, larger concentrations of SS-28 also hyperpolarized the neurons of the locus coeruleus and simultaneously decreased the input resistance. At the greatest concentration (20 psi x 5sec) applied, SS-28 produced complete inhibition of firing of all neurons tested; the inhibition was associated with a 11-mV hyperpolarization and decreased input resistance 9 percent. The voltage-current relationship of the resting cell revealed an inward-going rectification that became enhanced after the pressure application of SS-28. The reversal potential for the SS-28-induced hyperpolarization was -116 mV, which is approximately the potassium equilibrium potential. The results also showed that BaCl2 blocked the SS-28-induced hyperpolarization, but apamin did not. We conclude that the inhibitory actions of SS-28 are due to opening the inward-going rectification potassium channels and that SS-28 and somatostatin-14 exert similar electrophysiological actions on LC neurons.

Animals↗
PubMed1994

Regional changes in [3H]zolpidem binding to brain benzodiazepine receptors in flurazepam tolerant rat: comparison with changes in [3H]flunitrazepam binding.

Regional downregulation of brain benzodiazepine (BZ) receptors was studied in rats treated with flurazepam or diazepam protocols known to produce anticonvulsant tolerance. Zolpidem, a selective BZ1 receptor agonist, was used to detect BZ1 receptors; flunitrazepam, a nonselective BZ receptor agonist, was used to detect the total BZ receptor population. Rats were treated 4 weeks with flurazepam, then sacrificed immediately or 48 hr later. After flurazepam treatment, the maximal binding capacity of [3H]zolpidem binding decreased 22% in the cerebral cortex, 32% in the cerebellum and 25% in the hippocampus. The Kd increased in the cerebellum. The maximal binding capacity of [3H]flunitrazepam binding decreased by 13% in the cerebral cortex and 14% in the hippocampus, but did not change in the cerebellum. The Kd increased in the hippocampus. At 48 hr after flurazepam treatment, there was no significant difference in [3H]zolpidem binding between treated and control rats. In rats treated 3 weeks with diazepam released from s.c. reservoirs, there was no change in [3H]zolpidem binding. The data suggest that chronic flurazepam treatment causes downregulation primarily involving BZ1 receptors. The differing effects on [3H]-zolpidem and [3H]flunitrazepam binding, especially in the cerebellum in which more than 90% of the receptors are the BZ1 subtype, may indicate a shift in BZ receptor subtypes in flurazepam-tolerant rats, suggesting a change in the subunit composition or conformation of gamma-aminobutyric acidA/BZ receptors.

Animals↗
PubMed1994

Reduced expression of gamma-aminobutyric acid type A/benzodiazepine receptor gamma 2 and alpha 5 subunit mRNAs in brain regions of flurazepam-treated rats.

Previous studies showed that chronic benzodiazepine administration in rats affected the gamma-aminobutyric acid (GABA)A/benzodiazepine receptor. The present experiment investigated the effects of chronic flurazepam treatment on the mRNA levels for alpha 1, alpha 5, gamma 2, and gamma 2L (an alternatively spliced product of the gamma 2 gene) subunits of the GABAA/benzodiazepine receptor in rat cerebral cortex, cerebellum, and hippocampus. Rats were treated with flurazepam for 2 or 4 weeks, and the mRNA levels were measured while rats were still receiving drug or 48 hr after 4-week flurazepam treatment had been stopped. The level of alpha 5 mRNA was also measured in other rats 4 hr after a single injection of flurazepam or diazepam. The levels of mRNAs were analyzed by Northern blotting using digoxigenin-labeled oligonucleotide probes. Compared with the pair-handled controls, the levels of gamma 2 subunit mRNA in cortex and hippocampus were not changed after flurazepam treatment for 2 weeks. However, with rats treated with flurazepam for 4 weeks the levels of gamma 2 subunit mRNA were significantly reduced in cortex (31%) and hippocampus (39%) but not in cerebellum. The values returned to control levels by 48 hr after termination of the treatment. The regional distribution and time course of reduced gamma 2 levels matched the decrease in benzodiazepine binding produced by the same chronic flurazepam treatment. The amounts of alpha 5 mRNA were reduced in cortex (23%) and hippocampus (18%) 4 hr after a single dose of flurazepam but not diazepam. The levels of alpha 5 mRNA remained reduced in cerebral cortex and hippocampus (about 50%) after 2 weeks but returned to control after 4 weeks of chronic treatment with flurazepam. No change in alpha 1 or gamma 2L subunit mRNAs was observed in any of the three brain regions examined after 4 weeks of flurazepam treatment. These results suggest that benzodiazepine receptor down-regulation after chronic benzodiazepine treatment may be related to the reduced expression of gamma 2 subunit mRNA, and they also suggest differential temporal and regional regulation of alpha 5 and gamma 2 subunit mRNAs in rat brain.

Alternative Splicing↗
PubMed1993

Tolerance to the effects of diazepam, clonazepam and bretazenil on GABA-stimulated Cl- influx in flurazepam tolerant rats.

The effect of chronic flurazepam treatment on the GABA (gamma-aminobutyric acid) receptor/chloride channel complex was studied using GABA-stimulated 36Cl- influx into brain microsacs, and its potentiation by diazepam, clonazepam and bretazenil. Rats were given flurazepam for 1 week, then microsacs were prepared from cerebral cortices of rats that were still receiving flurazepam, and from those that had stopped treatment 48 h earlier. Diazepam and clonazepam produced concentration-dependent increases in GABA-stimulated 36Cl- influx while bretazenil produced a much smaller effect, which did not reach statistical significance in the tissue from control rats. There was no significant change in the basal or 10 microM GABA-stimulated 36Cl- influx between control and treated groups. Tolerance was shown by a significantly reduced effect of diazepam and clonazepam to enhance GABA-stimulated 36Cl- influx in the tissue prepared from non-withdrawn rats. However, for both diazepam and clonazepam, there was no tolerance 48 h after chronic treatment. The results suggest that changes in the GABA receptor/Cl- channel complex on cerebral cortical neurons contribute to cross-tolerance from flurazepam to other benzodiazepines.

Animals↗
PubMed1993

Biosynthesis and characterization of phosphatidylglycerophosphoglycerol, a possible intermediate in lipoteichoic acid biosynthesis in Streptococcus sanguis.

A membrane enzyme preparation from Streptococcus sanguis was shown to convert sn-[14C]glycerol 3-phosphate and CDP-diacylglycerol (or deoxyCDP-diacylglycerol) into a series of progressively higher-molecular-weight [14C]oligophosphoglycerophospholipids in vitro. The first oligophosphoglycerophospholipid to accumulate (termed lipid-1) was purified to homogeneity; chemical analysis, gas-liquid chromatography and chemical degradation studies indicated the most likely structure to be phosphatidylglycerophosphoglycerol (PGpG). PGpG is formed directly from two molecules of phosphatidylglycerol (PG), one molecule of PG serving as a sn-glycerol 1-phosphate (pG) donor and the second serving as the pG acceptor, with co-production of diacylglycerol. These oligophosphoglycerophospholipids may be intermediates in the biosynthesis of lipoteichoic acids.

Carbon Radioisotopes↗