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Biomedical subjects

T H Chiu

Publications and source records attributed to T H Chiu.

At least 91 records · Page 5Linked to original sources
PubMed1990

Modulation of GABA-stimulated Cl- flux by a benzodiazepine agonist and an 'inverse agonist' after chronic flurazepam treatment.

Rats treated one week with flurazepam were killed while still on the drug or 48 h after termination of drug treatment. The brain 'microsac' preparation derived from the cerebral cortices was used for studying the GABA-stimulated chloride influx. There was no significant change in the basal or GABA-stimulated influx between control and treated groups. However, the effect of flunitrazepam to enhance 10 microM GABA-stimulated influx was significantly reduced, indicating tolerance. Methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3- carboxylate (DMCM), an 'inverse agonist' at benzodiazepine receptors, dose dependently inhibited 50 microM GABA-stimulated influx; chronic treatment did not alter the effect of DMCM. This study demonstrates that one week treatment with flurazepam produces tolerance to benzodiazepines without any change in the effect of GABA or DMCM. This indicates that GABA and benzodiazepine sites are differently modulated after chronic treatment with benzodiazepines. However, since both benzodiazepine and DMCM act on the same receptors it appears that the different 'domains' on the benzodiazepine receptor are differently altered during chronic treatment.

Animals↗
PubMed1990

Tolerance to diazepam and methyl-beta-carboline-3-carboxylate measured in substantia nigra of benzodiazepine tolerant rats.

The spontaneous activity of neurons in the pars reticulata of substantia nigra (SNpr) was studied in chloral hydrate anesthetized rats. As a function of dose, intravenous diazepam decreased, and methyl-beta-carboline-3-carboxylate (beta CCM) increased discharge frequency. Two days after terminating a one week treatment with flurazepam (FZP), both diazepam and beta CCM showed decreased ability to alter SNpr neuronal activity. Neither residual FZP nor down-regulation of benzodiazepine receptors can account for these results. In contrast, behavioral testing revealed no change in the ability of i.v. beta CCM to cause convulsions, suggesting that sites other than the SNpr are of prime importance in expressing the convulsant actions of systemically injected beta CCM.

Animals↗
PubMed1990

Electrophysiological effects of dermorphin on locus coeruleus neurons of rat.

Intracellular recording was used to study the effects of dermorphin on neurons of the locus coeruleus in the rat, in a totally submerged brain slice preparation. Dermorphin caused the inhibition of spontaneous firing of all neurons of the locus coeruleus tested, with an IC50 of 7 nM. Based on the inhibition of spontaneous firing rate, dermorphin was 16.5 times more potent than morphine. Larger concentrations of dermorphin (30-100 nM) further hyperpolarized the neurons of the locus coeruleus and simultaneously caused a reduction in input resistance. These effects were antagonized by naloxone, with a dissociation equilibrium constant of 0.8 nM. The hyperpolarization of neurons of the locus coeruleus, caused by dermorphin, was reversed at a membrane potential of -112 mV in this preparation. Furthermore, this hyperpolarization was blocked by cesium chloride and barium chloride. Thus, these data suggest that dermorphin binds to mu-opioid receptors on the cell membrane of neurons of the locus coeruleus. This leads to opening of the inward-going rectification potassium channels, resulting in the observed hyperpolarization of the membrane.

Analgesics, Opioid↗
PubMed1989

Regional GABA/benzodiazepine receptor/chloride channel coupling after acute and chronic benzodiazepine treatment.

GABA/benzodiazepine coupling was evaluated in 8 regions of rat brain by the ability of GABA to stimulate 0.5 nM [3H]flunitrazepam binding. Rats were treated acutely with diazepam (p.o) or chronically with flurazepam, offered in the drinking water for 4 weeks, and compared to a pair-handled vehicle-treated control group. Regional variations in GABA/benzodiazepine coupling were found in control membranes. GABA increased benzodiazepine binding maximally (40%) in cerebellum and medulla, and least (25%) in olfactory bulb. A significant decrease in the effect of GABA was found in cortex of chronically treated rats immediately after, but not 2 days following treatment. The Emax for GABA stimulation of [3H]flunitrazepam binding was significantly increased in medulla after acute treatment but was not altered after acute or chronic treatment in other brain areas evaluated. Treatment had no effect on the ability of bicuculline to inhibit [3H]flunitrazepam binding in cortex. Benzodiazepine/Cl- coupling in cortex or hippocampus of acutely and chronically treated rats, evaluated by the ability of Cl- to stimulate specific [3H]flunitrazepam binding, was not changed. The results support the hypothesis that a functional uncoupling of the benzodiazepine recognition site from the GABA receptor in cortex, but not from the anion recognition site, may play a role in tolerance development.

Analysis of Variance↗
PubMed1989

[Incidental myomectomy in cesarean section].

In the retrospective study, from January 1984 to December 1987, incidental myomectomy was performed on 47 patients who received cesarean section. The control group consisted of 80 random samples who received cesarean section during the same period. The general information in both groups was similar. Postoperative infection rate was similar in both groups. Myomectomy added 11 minutes to the operation time, 112 milliliter to the operation blood loss and extended the hospital stay about one and a half day. Recovery of gastrointestinal tract function was one hour later in myomectomy group. There were no wound infection or serious morbidity in both groups. In order to estimate the value of incidental myomectomy in cesarean section, a further study of long term change of the myoma should be considered.

Abortion, Spontaneous↗
PubMed1989

Photoaffinity labeling of [3H]flunitrazepam- and [3H]Ro15-4513-bound pellets in rat cerebral cortex and cerebellum.

Irreversible incorporation of [3H]flunitrazepam and [3H]Ro15-4513 into GABA/benzodiazepine receptor subunits was studied by UV irradiation using ligand-bound membrane pellets from rat cerebral cortical and cerebellar synaptic membranes. Specific incorporation for [3H]flunitrazepam was greater in the pellet than in the suspension. The incorporation was identical for [3H]Ro15-4513 in both pellet and suspension. With the ligand-bound pellets, 50% of the available binding sites were photolabeled by both ligands in cortex and cerebellum. SDS polyacrylamide gel electrophoresis and fluorography of [3H]flunitrazepam photo-labeled receptor revealed the same number of major sites in both brain regions. In contrast, [3H]Ro15-4513 appears to label fewer sites in cortex and cerebellum. Photoaffinity labeling with [3H]flunitrazepam in ligand-bound membrane pellet provides a more selective and reliable method for studying the subunit structure of GABA/benzodiazepine receptor complex.

Affinity Labels↗
PubMed1989

Perinatal outcome of chorionic villus sampling versus amniocentesis.

This study assesses the relative risks of first trimester transcervical chorionic villus sampling (CVS) versus midtrimester amniocentesis performed between April 1986 and March 1988. The most common indication for prenatal diagnosis was advanced maternal age. We discovered 5.1% chromosomal aberrations in CVS compared to 1.0% in amniocentesis. Bleeding was the most frequent early complication, and only 1 case had major hemorrhage with subsequent spontaneous abortion. The fetal loss rate (gestational age less than 28 weeks) was 4.5% in CVS versus 1.2% in amniocentesis, which was not significantly different from the background fetal loss rate reported in normal pregnancies after an 8-week gestational age. Three cases of fetal loss after CVS were probably procedure-related; 1 case had spontaneous abortion and 2 cases had chorioamnionitis. Therefore, we considered that the causal relationship between CVS and the infection was highly probable. The clinical pregnancy outcome indicated that there were no differences in overall perinatal mortality, Apgar score, body weight, body length, gestational age at delivery, intrauterine growth retardation, placenta weight and placental disorders between the CVS group and the amniocentesis group. The pregnancies did not reveal any specific effects of the prenatal diagnostic procedure, but a long-term pediatric follow-up is needed.

Abortion, Spontaneous↗
PubMed1989

Selective continuation in quadruplets pregnancy following treatment of GIFT plus IVF and ET.

In this report, we present the selective reduction of quadruplets to triplets by transabdominal ultrasound guided cardiac puncture and injection of 1% xylocaine and air. This treatment resulted in the successful continuation of pregnancy until premature labor developed at the 33th week. Alive births of a normal male and a normal female infant, and a dead female infant were delivered.

Abortion, Induced↗
PubMed1988

Biosyntheses of galactosyl lipids and polysaccharide in Streptococcus mutans.

The syntheses of galactosylphospholipids and a galactose-containing polymer were observed when radio-labeled UDP-galactose was incubated with the membrane enzymes prepared from a strain of Streptococcus mutans, FA-1. The lipids were resolved into two components, lipids-1 and -2, by thin-layer and DEAE-cellulose column chromatographies. In the latter chromatography, lipid-1 was eluted by 0.0075 M and lipid-2 by 0.18 M ammonium acetate. The syntheses of lipids-1 and -2 were strongly inhibited by UDP and UMP, respectively. Both lipids-1 and -2 were degraded by mild acid, but were stable to mild alkaline hydrolysis. These results, together with their mobilities on thin-layer chromatography, suggest that lipid-1 is a galactosylphosphorylundecaprenol, and lipid-2 is a galactosylpyrophosphorylundecaprenol. When UDP-galactose was incubated with radiolabeled undecaprenol and ATP in the presence of membrane enzymes, lipids with thin-layer chromatographic mobilities of lipid-1 and lipid-2 were observed. The phosphate-to-galactose ratios in lipid-1 and lipid-2 were determined to be 1:1 and 2:1, respectively. These results indicated that lipid-1 and lipid-2 formed are galactosylmonophosphorylundecaprenol and galactosylpyrophosphorylundecaprenol, respectively. The polymer formed was eluted from the DEAE-cellulose column with a low concentration of salts (less than 0.1 M), suggesting that it is probably a polysaccharide, but not a lipoteichoic acid or teichoic acid-type polymer. In order to identify the sugars present in the polymer synthesized, the polymer purified by Sephadex G-50 and DEAE-cellulose column chromatographies was subjected to acid hydrolysis followed by NaB3H4 reduction and paper chromatographic analysis. [3H]Galactitol and a small amount of [3H]galactosaminitol were detected. This result suggests that the polymer is a nascent polysaccharide containing mainly galactose and a small amount of galactosamine, which probably derived from N-acetylgalactosamine during acid hydrolysis of the polymer.

Cell Membrane↗
PubMed1988

Effects of chronic flurazepam treatment on firing rate of rat substantia nigra pars reticulata neurons.

The effect of a benzodiazepine, flurazepam, on the spontaneous activity of neurons in the pars reticulata of the substantia nigra was studied in chloral hydrate anesthetized rats. Flurazepam produced a dose-related suppression of neuronal activity. In rats that were chronically treated with flurazepam, tolerance to flurazepam was present after 7 and 28 days, but not after only 3 days of treatment. Tolerance persisted at least 2, but not 7 days after 4 weeks of chronic treatment.

Action Potentials↗
PubMed1988

A comparison of the effects of midazolam and pentobarbital on the dose-response of GABA-gated Cl- influx in rat brain microsacs.

gamma-Aminobutyric acid (GABA)-gated Cl- influx was studied in a rat brain 'microsac' preparation. Midazolam (a benzodiazepine), at 0.1-10 microM, increased GABA potency (maximum 2-fold) without affecting its efficacy or exerting GABA-mimetic effect. Pentobarbital (10-500 microM) increased GABA potency (maximum 12-fold) and efficacy (maximum 40%). Pentobarbital exhibited GABA-mimetic effect at concentrations above 200 microM. The differential effects of midazolam and pentobarbital in modulating GABA-mediated responses may account for some of the differences between these two classes of drugs.

Animals↗
PubMed1988

Interactions of ACTH4-10 and ACTH1-24 with L-[3H]glutamate binding sites and GABA/benzodiazepine/picrotoxin receptor complexes in vitro.

The effects of ACTH4-10 and ACTH1-24 on L-[3H]glutamate (Glu) binding sites and GABA/benzodiazepine/picrotoxin receptor complexes in vitro were investigated. ACTH4-10 and ACTH1-24 inhibited [3H] Glu and [3H] muscimol binding concentration-dependently, while [3H] flunitrazepam (FNP) and [35S] t-butylbicyclophosphorothionate (TBPS) binding were not affected. These ACTH fragments also inhibited GABA-stimulated [3H] FNP binding. These results suggest that ACTH and its fragments may act as anticonvulsants by antagonizing glutamate binding, their interaction with GABA-A sites may relate to the other central nervous effects of ACTH than the anticonvulsant activity.

Adrenocorticotropic Hormone↗
PubMed1988

Modulation of GABA-gated chloride ion flux in rat brain by acute and chronic benzodiazepine administration.

gamma-Aminobutyric acid (GABA)-gated Cl- influx was studied in rat brain "microsacs." Midazolam caused a shift to the left of the GABA log dose-response curve. Pentobarbital produced a similar shift plus an increase in maximum response. Diazepam, flurazepam and desalkylflurazepam also enhanced GABA-gated Cl- flux. Their effects were blocked by Ro15-1788, a benzodiazepine antagonist. Acute diazepam pretreatment caused a shift to the left of the GABA dose-response curve but had no effect on the ability of benzodiazepines or pentobarbital to increase GABA-gated Cl- influx. In rats made tolerant by 4 weeks of flurazepam treatment, there was no decrease in the ability of GABA to mediate Cl- flux. GABA was more potent in microsacs from nonwithdrawn rats. In rats withdrawn for 12 but not 48 hr, the maximum GABA response was increased. The ability of benzodiazepines and of pentobarbital to enhance GABA-gated Cl- influx was reduced, showing tolerance. However, 2 days after withdrawal from chronic treatment, this was no longer statistically significant. The results show that benzodiazepine tolerance involves reduced functional coupling between the benzodiazepine recognition site and the GABA recognition site-Cl- channel. Furthermore, reduced effectiveness of GABAA agonists in benzodiazepine-tolerant animals might result from alterations in neuronal activity that occur subsequently to activation of the GABA receptor-gated anion channel.

Animals↗
PubMed1988

Experience with fully bioresorbable aortic grafts in the dog.

Reorganization of the arterial wall through natural processes on the resorption of a totally bioresorbable graft was investigated in dogs with Vicryl prostheses coated with two different blends of bioresorbable polyesters capable of slowing down considerably the disintegration of a Vicryl fabric in vivo. The prostheses (8 to 9 mm in internal diameter, 8 to 10 cm long) were implanted in the infrarenal aortic position for up to 24 weeks. All 18 animals implanted with coated prostheses survived, whereas one animal implanted with an uncoated Vicryl prosthesis died because of early rupture of the graft. Patent tubular conduits were present in 14 animals at the time of retrieval. On resorption of the synthetic polymers, the tissue layers that formed on both sides of the prosthetic material either fused or remained separated, depending on the polymer used as a retardant coating. We conclude that polymer composition influences the repair process and that a fully resorbable vascular graft can function effectively in a canine model, provided that tissue organization is sufficiently advanced by the time the prosthesis has lost its mechanical integrity. Further studies are needed to document the performance of the newly formed blood conduit over extended periods, in hypertensive subjects, and when presented with a bacterial challenge.

Absorption↗
PubMed1987

Peripheral nerve regeneration with entubulation repair: comparison of biodegradeable nerve guides versus polyethylene tubes and the effects of a laminin-containing gel.

These experiments present quantitative data concerning peripheral nerve regeneration in vivo. We used entubulation repair as a model to compare two different types of tubular prostheses, one nonbiodegradable and the other biodegradable. We modified the microenvironment of the regenerating axons within the tubular prostheses by adding a laminin-containing gel to the interior of the tube at the time of initial implantation. The data demonstrate that specific manipulations to the microenvironment of regenerating peripheral axons have quantitative effects on the rate and extent of nerve regeneration. Such effects were dependent on the composition of the tubular prosthesis and varied according to the survival time of the animals. For instance, the laminin gel within the biodegradable tubes enhanced nerve regeneration at 2 weeks but was inhibitory at 6 weeks. Furthermore, such manipulations may have different effects on the number of myelinated axons found within the regenerating nerve cable versus the number of primary motor and sensory neurons giving rise to such axons. We concluded that: the presence of a laminin-containing gel significantly increased the initial rate at which axons from primary sensory and motor neurons cross a transection site; an initial delay in axonal outgrowth at early time points did not necessarily predict diminished outgrowth at later times; and because of the potential for axonal branching the number of myelinated axons found in the midportion of a tubular prosthesis did not always correlate with the number of primary motor and sensory neurons which gave rise to those axons.

Animals↗
PubMed1987

Somatostatin effects in isolated human atrial fibres.

Effects of hypothalamic hormone somatostatin on the action potential and contractile force of 54 human atrial preparations obtained at cardiac surgery were studied with standard microelectrode techniques. In the atrial fibres responding to electrical stimuli with fast response action potentials in 4 mM [K]0 Tyrode solution (maximum rate of phase 0 depolarization greater than 50 V/s), somatostatin (10(-7) to 10(-6) M) reduced slightly the duration of action potential and decreased twitch force dose-dependently. In spontaneously active atrial fibres, somatostatin (10(-7) to 10(-6) M) abolished the action potentials in the preparations with low maximal diastolic potential (MDP, -48 +/- 2.8 mV), but induced only mild suppressive effect in the preparations with high MDP (-70 +/- 2.4 mV). When the fibres were depolarized in 27 mM [K]0 Tyrode solution, somatostatin decreased the maximum rate of depolarization and amplitude of the slow response action potentials induced by electrical stimuli. The delayed afterdepolarizations or triggered action potentials induced by high-frequency electrical drive in the presence of epinephrine were also suppressed by somatostatin. The above findings suggest that somatostatin may suppress the abnormal automaticity and the triggered activity in human atrial fibres through a reduction of cellular calcium.

Action Potentials↗
PubMed1986

GABA-gated chloride ion influx and receptor binding studies in C57BL6J and DBA2J mice.

GABA-gated chloride ion influx was measured in brain 'microsac' preparations of young (20-22-day-old) and older (40-42-day-old) C57BL6J and DBA2J mice. The young DBA2J mice are susceptible to audiogenic seizures. GABA sensitivity was reduced in young DBA2J mice as compared to age-matched C57BL6J mice or older mice of either strain. Age and strain differences in ligand binding to GABA/benzodiazepine receptor complex and glutamate receptor could not account for this finding. These results provide evidence for a defect in GABA-gated chloride ion influx in audiogenic seizure-susceptible DBA2J mice.

Age Factors↗