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Biomedical subjects

T H Chiu

Publications and source records attributed to T H Chiu.

At least 19 recordsLinked to original sources

The antral follicle count predicts the outcome of pregnancy in a controlled ovarian hyperstimulation/intrauterine insemination program.

PURPOSE: Our purpose was to test whether age-related changes in antral follicle counts can predict the pregnancy outcome in the early follicular phase of a controlled ovarian hyperstimulation/intrauterine insemination (COH/IUI) program. METHODS: A selected group of 107 women (36 healthy women requesting child sex preselection, 52 women with unexplained infertility, and 19 with minimal endometriosis) who underwent controlled ovarian hyperstimulation with clomiphene citrate (CC) plus human menopausal gonadotrophin (hMG) and subsequent intrauterine insemination were enrolled in the study. Transvaginal ultrasonography (7.0 MHz) was used to determine the total number of antral follicles (2-8 mm) in the right and left ovaries. The association among the antral follicle count, age, dominant follicle, and estradiol (E2) level on the day of human chorionic gonadotropin (hCG) was analyzed. The association of the pregnancy rate and OHSS with the antral follicle count, dominant follicle count, and age was also examined. RESULTS: The total antral follicle number decreased with age (P < 0.0001). Dominant follicle number increased with total antral follicle number in women who received CC plus hMG/ IUI(P < 0.0001). The pregnant group had a higher number of antral follicle and dominant follicles in comparison with the nonpregnant group (P < 0.01 and P < 0.02, respectively). The E2 level on the day of hCG injection increased positively with the total number of antral follicles (P < 0.0001) and the total number of dominant follicles (P < 0.0001). In women aged younger than 35 years, the pregnancy rate and dominant follicle number rose as the number of antral follicles increased (P < 0.03 and P < 0.0001, respectively). The pregnancy rate was low (2/39) in women aged older than 35 years regardless of the number of antral follicles (P < 0.05) and the extent of hMG administration (P < 0.02). Women aged older than 35 also produced fewer dominant follicles (P < 0.001). No pregnancy was achieved in a patient with an antral follicle number of less than five (17 cases). CONCLUSIONS: Age-related changes in antral follicle count significantly predicted the dominant follicle count and the pregnancy outcome. In women with antral follicle counts of less than five or who are older than 35 years, the application of COH/IUI may not be indicated.

Age Factors

Opioid and antiopioid actions of Tyr-MIF-1, Tyr-W-MIF-1 and hemorphin-4 on rat locus coeruleus neurons: intracellular recording in vitro.

Intracellular recording was used to study the effects of naturally occurring opioid tetrapeptides, including Tyr-Pro-Leu-Gly-NH2 (Tyr-MIF-1), Tyr-Pro-Trp-Gly-NH2 (Tyr-W-MIF-1), and Tyr-Pro-brain slice preparation. These tetrapeptides which, like other opioids, caused inhibitory effects on all LC neurons tested. Tyr-MIF-1 (10-100 microM), Tyr-W-MIF-1 (1-10 microM) and hemorphin-4 (1-30 microM) caused dose-related inhibition of the spontaneous firing. The IC50 were 37.5, 3.8 and 6.7 microM for Tyr-MIF-1, Tyr-W-MIF-1 and hemorphin-4, respectively. In addition, these tetrapeptides were tested for their blocking effects on the Tyr-D-Arg-Phe-sarcosine-OH (TAPS)-induced inhibitory actions. The results showed that Tyr-MIF-1, Tyr-W-MIF-1 and hemorphin-4 significantly decreased the actions of lower concentration of TAPS (30 nM), but did not decrease the actions of higher concentration of TAPS (100 nM). It is concluded that the blood-derived peptide hemorphin-4 and the endogenous peptides Tyr-W-MIF-1 and Tyr-MIF-1 possess opioid and antiopioid actions in the LC neurons.

Animals

Hypoxia-induced differential electrophysiological changes in rat locus coeruleus neurons.

The effects of hypoxia on rat locus coeruleus (LC) neurons were investigated by intracellular recording from in vitro brain slices. In response to a brief exposure to hypoxic medium (2-5 min), equilibrated with 95% N2 - 5% CO2, two populations of cells could be distinguished, type 1 neurons (61%), showing hyperpolarization (9.3 +/- 0.4 mV, n = 125) and cessation of spontaneous action potentials, and type 2 neurons (39%), displaying gradual pure depolarization (6.0 +/- 0.3 mV, n = 80), instead of hypoxic hyperpolarization. Both types of response were associated with a reduction in membrane input resistance (34 +/- 1% for type 1 cells, n = 125, and 21 +/- 2% for type 2 cells, n = 68). While both types of neurons share similar electrophysiological properties, their membrane input resistance differ significantly (type 1 cells: 144 +/- 5 M omega, n = 125; type 2 cells: 183 +/- 9 M omega, n = 80, p < 0.001). These responses were compared to cyanide-induced chemical hypoxia. Cyanide (2 mM) induced the identical membrane response as effected by nitrogen hypoxia. All cells which responded to nitrogen-saturated hypoxic medium with a pure depolarizing response gave a similar response to cyanide and all neurons hyperpolarized by cyanide were also hyperpolarized by hypoxic medium. Moreover, the K(ATP) channel opener, diazoxide (1 mM), could mimic the hypoxia-induced hyperpolarization in type 1 neurons (10.6 +/- 0.9 mV, n = 18), but was unable to induce hyperpolarization in type 2 cells (n = 13). In addition, the N2-hypoxia-induced hyperpolarization was completely blocked by tolbutamide (200 microM, n = 8) or glibenclamide (3 microM, n = 9). These results indicate that a brief period of hypoxia evokes two different responses in LC neurons and this may be due to the heterogeneous distribution of K(ATP) channels among different LC neurons.

Animals

Effects of glucose on placental hormones in the human term placenta in vitro.

Glucose intake during pregnancy results in a decrease in endogenous insulin-like growth factor binding protein-1 (IGFBP-1). However, the exact role of glucose on placental secretion of IGFBP-1 is unclear. This study was designed to investigate the direct effects of glucose on the production of IGFBP-1 and other placental hormones, using an isolated placental preparation. Using the dual recirculating perfusion system for an isolated human placenta lobule, a total of 43 experiments were performed over a duration of 6 hours. Twenty placentae were perfused with a medium containing 141 +/- 10 mg/dL (7.83 +/- 0.56 mmol/L) glucose (group I) and 23 placentae with 242 +/- 12 mg/dL (13.43 +/- 0.67 mmol/L) glucose (group II). Levels of insulin, glucose, lactate, insulin-like growth factor (IGF-I), IGFBP-1, human placental lactogen (hPL) and beta-human chorionic gonadotropin (beta-hCG) were measured at 30 minute intervals during perfusion. Insulin and IGF-I were barely detectable in the perfusates and their levels were not modulated by glucose. IGFBP-1 was predominantly detected in the maternal rather than the fetal compartment of the placental circulation. Glucose increased the levels of IGFBP-1 in the maternal circulation in groups I and II during the first two hours of perfusion (188 +/- 58% and 193 +/- 31%, respectively). However, during the subsequent 4 hour period, the increase in IGFBP-1 concentration was significantly higher in group II (926 +/- 427%) than in group I (428 +/- 216%) (p < 0.05). There was no difference in the levels of hPL or beta-hCG between the two groups in the maternal circulation. Thus, glucose stimulates the production of IGFBP-1 in the maternal circulation of a placenta in vitro. This increase in IGFBP-1 by glucose in vitro, as opposed to the decrease of IGFBP-1 in vivo, may be due to a lack of circulatory maternal insulin in the isolated placental preparation. These results also suggest that there may be a functional barrier within the placenta that prevents an increase in the level of IGFBP-1 in the fetal circulation.

Chorionic Gonadotropin, beta Subunit, Human

Prenatal diagnosis of congenital cystic adenomatoid malformation of the lung: four cases report.

Congenital cystic adenomatoid malformation of the lung (CCAML) is a rare pulmonary lesion, characterized by excessive overgrowth of the terminal respiratory bronchioles. Prenatal detection and serial sonographic study of fetuses with CCAML can provide information about the natural history of these lesions and reveal most of the nature history of pathophysiologic features which are likely to affect the clinical outcome. This information is crucial to the formulation of a prognosis and a management strategy. We report on four cases of CCAML, three of which involved macrocystic lesions including two cases of type I and one case of type II. Only one microcystic lesion, a type III CCAML, was identified in these patients. All of the cases were diagnosed by ultrasound between the 21 and 24 weeks of gestation. Fetal hydropic change was noted in all four cases. All of the parents opted for termination of pregnancy before fetal viability. Post-mortem examination confirmed the diagnosis in all four cases.

Adult

Treatment with an antisense oligodeoxynucleotide to the GABAA receptor gamma 2 subunit increases convulsive threshold for beta-CCM, a benzodiazepine "inverse agonist', in rats.

The gamma 2 subunit of the gamma-aminobutyric acid type-A (GABAA) receptor is associated with the actions of benzodiazepines and related drugs. A phosphorothioate-modified antisense oligodeoxynucleotide directed against the gamma 2 subunit was given by i.c.v. injection (18 micrograms in 2 microliters saline) to male Sprague-Dawley rats every 12 h for 3 days. Controls received the corresponding sense oligodeoxynucleotide. 4-6 h after the last i.c.v. treatment, rats were given methyl-beta-carboline-3-carboxylate (beta-CCM), a benzodiazepine "inverse agonist', by slow i.v. infusion. Compared to naive rats, the beta-CCM threshold dose was not affected by the sense oligodeoxynucleotide, but was increased 87% in antisense oligodeoxynucleotide-treated rats. The treatment had no effect on the seizure threshold for picrotoxin. Both antisense and sense oligodeoxynucleotide treatments slightly increased the threshold for strychnine seizures. The results suggest that antisense oligodeoxynucleotide treatment altered GABAA receptor composition and interfered with the actions of a benzodiazepine receptor ligand in vivo, and may provide a tool for studying regulation of receptor structure and function.

Analysis of Variance

Chronic exposure of neonatal cardiac myocytes to hydrogen peroxide enhances the expression of catalase.

The adaptive response of antioxidant enzymes to oxidative stress in the heart has not been investigated. Because H2O2 is considered to play a major role in reperfusion injury to the heart, this study was undertaken to examine if H2O2 alters the expression of these enzymes in the rat neonatal myocytes. H2O2 was continuously generated by the addition of glucose oxidase to the culture medium. Both the activity and the mRNA for catalase were increased following incubation of neonatal myocytes with non-toxic concentrations of glucose oxidase. The induction of mRNA preceded the enhancement of activity, and both remained elevated after 24 h incubation. Nuclear run-on assay indicated that the transcriptional rate for catalase mRNA was increased. The same treatment did not alter the activities for total superoxide dismutase and Se-glutathione peroxidase. The results suggest that H2O2-induced expression of catalase was in part due to transcriptional activation. It further implies that the induction of catalase may play an important role in protecting hearts from ischemic/reperfusion injury.

Animals

Antioxidant enzyme gene transcription in copper-deficient rat liver.

Antioxidant enzymes, Cu/Zn- and Mn-superoxide dismutase, catalase, and glutathione peroxidase, constitute an important defense mechanism against cytotoxicity of reactive oxygen species. Copper is essential for the activity of Cu/Zn-superoxide dismutase. Oxidative stress, therefore, is expected in organs of rats fed copper-deficient diet due to reduced Cu/Zn-superoxide dismutase activity. Our previous studies have shown that the expression of antioxidant enzymes was altered in copper-deficient rat liver. The present report was undertaken to study further the transcription of these enzymes in liver nuclei of rats made copper-deficient for 4 weeks. While copper deficiency decreased the copper in liver by about 80%, it did not alter the copper content in liver nuclei. In spite of a 100% elevation in nuclear iron concentration, liver nuclei from copper-deficient rats showed normal appearance. The transcriptional rates for Cu/Zn-superoxide dismutase, glutathione peroxidase, and glyceraldehyde-3-phosphate dehydrogenase were not altered by dietary copper deprivation. In contrast, transcriptional rates for Mn-superoxide dismutase and beta-actin were increased but that for catalase was reduced in the nuclei isolated from the copper-deficient rat liver. These results suggest that oxidative stress, resulting from copper deficiency, differentially modulates the gene transcription for the antioxidant enzymes in rat liver.

Animals

Prenatal diagnosis of major congenital cardiovascular malformations.

This prospective study was designed to determine whether there would be a higher incidence of congenital cardiovascular malformation (CCVM) in pregnant women with certain risk factors. Fetal echocardiography, from second trimester of term, was performed in 1,659 pregnant women with risk factors for CCVMs and 826 pregnant women without risk factors from March 1990 to April 1995. Two-dimensional imaging, fetal M mode measurements, Doppler waveform velocity and Doppler color flow mapping were used for fetal heart examination. During this period, 70 fetuses with major cardiovascular malformations were found. The prenatal detection rate was determined as 2.8% (70/2,485) in our study. The rate in the high-risk group, however, was 3.7% (61/1,659). Of all indications, fetal risk factors had the highest rate (9.3%, 46/494) of detected CCVMs. Maternal and familial indications could be excluded from the high-risk group as they did not show any increased incidence over the low-risk group. We suggest that fetal echocardiography is mandatory in the high-risk group, especially in cases with fetal and placental risk factors. Fetal cardiac screening in the hands of first-line sonographers has a major role in prenatal diagnosis of CCVMs in the low-risk group.

Echocardiography

Action of dexmedetomidine on rat locus coeruleus neurones: intracellular recording in vitro.

The action of dexmedetomidine on rat locus coeruleus neurones was examined using intracellular recordings from the in vitro brain slice preparation. Concentrations of dexmedetomidine from 1 to 1000 nM were tested. At 30 nM, dexmedetomidine produced complete inhibition of firing of all neurones tested (n = 21); this was associated with a 13 mV hyperpolarization (range 2.2-29.7 mV, n = 21) and a 27% reduction in input resistance (range 11.1-46.2%, n = 17). The dexmedetomidine responses reached a plateau phase between 100 and 1000 nM. Based on single-cell recordings, the hyperpolarizing potency of dexmedetomidine was found to be 6 times greater than that of clonidine (n = 10). The reversal potential for the dexmedetomidine-induced hyperpolarization was -106.9 +/- 1.7 mV (n = 9), a value similar to the K+ equilibrium potential; hyperpolarization was blocked by both CsCl and BaCl2. The effect of dexmedetomidine was antagonized by yohimbine, with a dissociation equilibrium constant of 30 nM. In contrast, prazosin, the alpha 1-, alpha 2B- and alpha 2C-adrenoceptor subtype-preferring ligand, did not inhibit the dexmedetomidine effect. Our results also show that low concentrations of oxymetazoline (10-300 nM), an alpha 2A-adrenoceptor subtype-selective drug, cause profound inhibition of neuronal activity in the locus coeruleus. These data therefore suggest that dexmedetomidine binds to alpha 2A-adrenoceptors on the cell membrane of neurones of the locus coeruleus and that this leads to opening of the inwardly rectifying K+ channels, resulting in the observed hyperpolarization of the membrane.

Adrenergic alpha-2 Receptor Agonists

Rapid down-regulation of [3H]zolpidem binding to rat brain benzodiazepine receptors during flurazepam treatment.

In a previous study, it was found that down-regulation of benzodiazepine (BZ) binding in rats treated 4 weeks with flurazepam was relatively greater and more widespread when measured with [3H]zolpidem, a selective 'BZ1 receptor' ligand, than that measured with the non-selective ligand, [3H]flunitrazepam. In the present study, the time course for down-regulation of [3H]zolpidem binding was studied in rats treated with flurazepam. [3H]Zolpidem binding was also studied in rats given a midazolam treatment shown to cause tolerance. Rats were chronically treated with flurazepam for 1 or 2 weeks, or with midazolam for 3 weeks, then killed immediately after the treatment. Another group of rats was acutely treated with desalkyl-flurazepam and killed 30 min later. After 2 weeks of flurazepam treatment, the Bmax of [3H]zolpidem binding was decreased by 22% in cerebral cortex, 26% in cerebellum and 33% in hippocampus, with no change in the Kd in any region. After 1 week of flurazepam treatment, the Bmax was decreased by 23% in cerebellum and 14% in hippocampus, but not changed in cerebral cortex. The Kd was increased in cerebral cortex, but not in cerebellum or hippocampus. Neither the Bmax nor the Kd of [3H]zolpidem binding was affected by acute desalkyl-flurazepam treatment, or by 3 weeks of midazolam treatment. These results, in combination with previous findings, which showed no change in [3H]flunitrazepam binding after 1 or 2 week flurazepam treatment, and no change in cerebellum even after the 4 week treatment, may indicate a shift in BZ receptor subtypes in flurazepam-tolerant rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Methotrexate treatment of cervical pregnancies with different clinical parameters. A report of three cases.

Three cases of cervical pregnancy with different clinical parameters were successfully treated with methotrexate. Case 1 was a viable cervical pregnancy, case 2 was a cervical pregnancy after curettage that developed into a cervical hematoma, and case 3 was a cervical pregnancy at an early gestational age. The interval between diagnosis and treatment ranged from 45 to 76 days. The maximum quantitative beta-human chorionic gonadotropin (beta-hCG) levels in cases 1, 2 and 3 were 100,180, 19,093 and 956 mIU/mL, respectively. These patients showed a progressive decline in beta-hCG levels, and ultrasound showed a gradual decrease in the size of the pregnancies. The interval between treatment and beta-hCG resolution ranged from 14 to 59 days. Only in case 2 did side effects occur, including stomatitis and transient elevation of serum transaminase. In view of the risks of standard therapy and patients' desire for fertility, methotrexate treatment may be a therapeutic alternative for cervical pregnancy.

Adult

Congenital malformation in newborns. Analysis of 501 cases.

Over a 14-year period in Chang Gung Memorial Hospital, 510 out of 44, 362 newborns were found to have birth defects. Maternal age, gestational age, parity, infant sex and birth weight were analyzed for each anomaly and compared to normal newborns. The average maternal age and parity for newborns with congenital anomalies were not significantly different from normal newborns. Mothers giving birth to babies with chromosomal aberrations, however, had a significantly older maternal age than the normal population. The gestational age at delivery was significantly shorter for all except craniofacial anomaly. In addition, there was a high percentage of intrauterine growth retardation in congenital anomalies. The central nervous system, the musculoskeletal system and craniofacial systems were the most commonly involved. The leading anomalies included cleft lip, cleft palate, anencephaly, polydactyly, hydrops fetalis, trisomy 21 and cystic hygroma. With improved ultrasound equipment and other prenatal diagnostic procedures, many defects of the fetus can now be identified. If the fetus is diagnosed with a surgically correctable lesion like cleft lip, it can be kept to term, delivered, then managed postnatally. If life-incompatible malformations have been detected before the 24th week, physicians are in a good position to counsel the parents. After the 24th week termination is proscribed by law. Therefore, physicians must take special care to detect fetal abnormalities early.

Congenital Abnormalities

Altered expressions of cardiac Na/K-ATPase isoforms in copper deficient rats.

OBJECTIVE: The aim was to determine if copper deficiency affects the expression of Na/K-ATPase alpha isoforms in the rat heart. METHODS: Copper deficiency was induced by placing weanling rats on a copper deficient diet for 4-5 weeks. Adult ventricular tissue, isolated ventricular myocytes, and brain stems of the control and deficient rats were compared for Cu, Zn-superoxide dismutase (CuZn-SOD) activity and for protein and mRNA contents of Na/K-ATPase alpha isoforms. RESULTS: In brain stem, where copper deficiency did not alter CuZn-SOD activity, mRNA and protein levels of alpha isoforms also remained unchanged. In ventricular tissue and ventricular myocytes, copper deficiency reduced CuZn-SOD activity, mRNAs of alpha 1 and alpha 2 isoforms, and the alpha 2 isoform protein. The alpha 1 isoform protein of ventricular tissue and its myocytes was marginally reduced by copper deficiency. CONCLUSIONS: In the rat ventricular tissue, oxidative stress resulting from copper deficiency (1) enhances the turnover of the more oxidant sensitive alpha 2 isoform to a greater extent than the turnover of the alpha 1 isoform; (2) regulates mRNA levels of alpha 1 and alpha 2 isoforms; and (3) contributes to the cardiomyopathy of copper deficiency.

Animals

Prenatal diagnosis of tetralogy of fallot by Doppler color flow mapping.

The prenatal diagnosis of tetralogy of Fallot (TOF) can be difficult, as the routine sonographic four-chamber view may be normal before birth. Unlike the normal fetus, in which blood flows adjacent to the left side of the interventricular septum, on color Doppler mapping a fetus with TOF also demonstrates antegrade flow along the right side of the interventricular septum. This Y-shaped ventricular outflow passing through the dilated aortic tract is confluent at the level of the ventricular septal defect during the systolic phase. In the past 3 years, three cases of TOF have been diagnosed prenatally at the Chang Gung Memorial Hospital. In each case, the above picture was demonstrated. 2-Dimensional Doppler color flow mapping may be helpful in the prenatal diagnosis of TOF.

Adult

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