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Biomedical subjects

S H Hsiao

Publications and source records attributed to S H Hsiao.

10 recordsLinked to original sources
PubMed2001

Early postnatal ethanol intubation blunts GABA(A) receptor up-regulation and modifies 3alpha-hydroxy-5alpha-pregnan-20-one sensitivity in rat MS/DB neurons.

Previously we found postnatal binge-like ethanol exposure using an artificial-rearing method in the rat delayed developmental up-regulation of GABA(A) receptors (GABA(A)Rs) in both medial septum/diagonal band (MS/DB) and cerebellar Purkinje neurons. In the present study, the impact of ethanol on developing GABA(A)Rs in MS/DB neurons was further tested under conditions not requiring anesthesia or maternal deprivation. Nursing rat pups received ethanol (4.5-5.25 g/kg/day) on postnatal days (PD) 4-9, which was administrated manually by oral intragastric intubation. This treatment caused dose-dependent blunting of peak GABA(A) receptor whole cell currents in acutely dissociated MS/DB cells on PD 12-15. The threshold with oral intubation was slightly higher than previously observed for artificial-rearing (4.9 vs. 4.5 g/kg/day). The previously observed reduced sensitivity of GABA(A)Rs to Zn(2+)-inhibition after ethanol was not found with the intubation model. In studies only carried out using the intubation method, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha-OH-DHP) caused an allosteric concentration-dependent potentiation of currents activated by non-saturated concentrations of GABA. A bicuculline sensitive direct activation of GABA(A)Rs also occurred with higher concentrations of 3alpha-OH-DHP alone. Ethanol intubation up-regulated allosteric neurosteroid potentiation with low concentrations of GABA, but did not change direct agonist actions of 3alpha-OH-DHP. Finally, 3alpha-OH-DHP did not prime ethanol insensitive GABA(A)Rs to become sensitivity to acute ethanol potentiation. These results indicate ethanol consistently blunts postnatal GABA(A) receptor up-regulation across early postnatal binge-type ethanol exposure models and may increase positive modulation of GABA(A) receptors by endogenous neurosteroids.

Age Factors↗
PubMed1999

Postnatal ethanol exposure blunts upregulation of GABAA receptor currents in Purkinje neurons.

Recently, we found that early postnatal ethanol exposure inhibits the maturation of GABAA receptors (GABAARs) in developing medial septum/diagonal band (MS/DB) neurons, suggesting that these receptors may represent a target for ethanol related to fetal alcohol syndrome (FAS). To determine whether GABAARs on other neurons are also sensitive to a postnatal ethanol insult, postnatal day (PD) 4-9, rat pups were artificially reared and exposed to ethanol (4.5 g kg-1 day-1, 10.2% v/v). The pharmacological profile of acutely dissociated cerebellar Purkinje cell GABAARs from untreated, artificially reared controls and ethanol-treated animals was examined with conventional whole-cell patch clamp recordings during PD 12-16 (juveniles) and PD 25-35 (young adults). For untreated animals, GABA (0.3-100 microM) consistently induced inward Cl- currents in a concentration-dependent manner showing an age-related increase in maximum response without change in EC50 or slope value. Acute ethanol (100 mM) consistently inhibited 3 microM GABA currents (10-20%); positive modulators, pentobarbital (10 microM), midazolam (1 microM) and loreclezole (10 microM), consistently potentiated; the negative modulator, Zn2+ (30 microM), inhibited GABA currents across both juvenile and young adult groups. Loreclezole potentiation increased while Zn2+ inhibition decreased with age in untreated Purkinje neurons. Postnatal ethanol exposure (PD 4-9) decreased GABAAR maximum current density in young adult Purkinje cells but not in juvenile neurons. However, sensitivity to allosteric modulators did not change after ethanol. These data are consistent with the hypothesis that postnatal ethanol exposure during the brain growth spurt can disturb GABAAR development across the brain, although the mechanism(s) underlying this action remains to be determined.

Allosteric Regulation↗
PubMed1998

Development of GABAA receptors on medial septum/diagonal band (MS/DB) neurons after postnatal ethanol exposure.

The impact of 'binge-like' ethanol exposure on postnatal days (PD) 4-9 was examined on development of gamma-aminobutyric acid type A receptors (GABAAR) during the first month of life in the rat. Whole-cell patch-clamp recordings in acutely isolated medial septum/diagonal band (MS/DB) neurons were used to define effects of rapidly applied ethanol and other allosteric modulators on bicuculline-sensitive GABA currents. Three age groups were examined including 'pups' (PD 4-10), 'juveniles' (PD 11-16) and 'young adults' (PD 25-35). In untreated neurons, maximum responses to GABA and the apparent GABA EC50 increased approximately 2-fold during the first month of life. Potentiation of GABA responses by pentobarbital, midazolam, and loreclezole all increased with age, while Zn2+ inhibition declined. Initial inhibition by ethanol switched to potentiation of GABA responses during this time. In vivo, binge-like ethanol treatment (4.5 g kg-1 day-1 divided into two doses, 2 h apart on PD 4-9) reduced both the GABA maximal response and GABA EC50 measured on PD 11-16. These measures returned to control levels by PD 25-35. After binge-like postnatal ethanol exposure, age-dependent loss of Zn2+ inhibition of GABA responses was increased, while potentiating actions of in vitro ethanol were blocked. GABAAR modulation by other drugs was unaffected. These data suggest that early postnatal ethanol exposure disrupts the expected developmental pattern of GABAAR function in MS/DB neurons, an action that could contribute to neurobehavioral deficits associated with the fetal alcohol syndrome. Whether these changes are due to cellular damage, delayed gene expression or post-translational modification needs to be determined.

Algorithms↗
PubMed1997

Traumatic brainstem deafness with normal brainstem auditory evoked potentials.

A 48-year-old woman became totally deaf after a head injury. Magnetic resonance imaging showed bilateral contusions around the inferior colliculi and the brainstem auditory evoked potentials (BAEP) failed to show any abnormality. This case demonstrates that small, symmetrical, bilateral lesions around the inferior colliculi may cause deafness and may still be associated with a normal BAEP.

Auditory Pathways↗
PubMed1994

[A replication of multidimensionality of activities of daily living(ADL): on the elderly in southern Taiwan].

The purpose of the present study is to test whether Wolinsky and Johnson's declaration that activities of daily living (ADL) can be divided into three subdimension (basic, household, and advanced ADL), and whether these three dimensions could be replicated or not in Taiwan. Furthermore, to confirm the relationship of advanced ADL and cognitive function. The analyses were based on a sample of 790 respondents over 65 years of age who lived in the community of Southern Taiwan. Fourteen items were adopted from the ADL section of OARS Multidimensional Functional Assessment (OMFAQ, Chinese Version) for performing a confirmatory factor analysis. In addition, 10 items from the Short Portable Mental Status Questionnaire (SPMSQ) were selected for a zero-order correlation and regression analyses to examine the relationship between the advanced ADL and cognitive function. The results support Wolinsky & Johnson's assertion, but some items that are comprised in each factor structure, however, are not consistent with those in Wolinsky & Johnson's study, such as taking medicine, grooming, eating, shopping, and transporting. Significant correlation between advanced ADL and cognitive function was also confirmed in the study (r = 0.612, p < 0.05).

Activities of Daily Living↗
PubMed1994

[A comparison on health status between Paiwan and Min-Nan elderly].

The study investigated the Taiwanese elderly in two different ethnic groups (Paiwan and Min-Nan) regarding their multifunctional status. The purpose was to make known and compare the subjective and objective health status of these two groups. The results for the objective measurements indicated that an elderly Paiwanese had 2.74 kinds of diseases on average. The most prevalent diseases among the Paiwan elderly were arthritis (rheumatism), circulation troubles in arms or legs, high blood pressure, stomach or intestinal disorders or gall bladder problems, cataract, heart trouble, emphysema (chronic bronchitis), skin disorder (leg ulcers or severe burns), asthma, and digestive system ulcers. Of all disease, five (arthritis, circulation trouble, emphysema, skin disorder, and tuberculosis) were statistically more prevalent among the Paiwan elderly than among the Min-Nan elderly. In terms of health scoring, the two groups were comparable except in the following two aspects: (1) more Paiwan elderly were unable to take medicine by themselves, and (2) the Paiwan elderly had lower cognitive ability ratings. In the subjective arena, the Paiwan elderly had a lower score in self-rating health status. Condensed, the health status of the Paiwan was worse than that of the Min-Nan elderly both in objective and subjective measurements.

Aged↗
PubMed1993

Combination cytotoxic effects of cis-diamminedichloroplatinum(II) and 5-fluorouracil with and without leucovorin against human non-small cell lung cancer cell lines.

Both cisplatin (CDDP) and leucovorin (LV) have been shown to enhance cytotoxicity of 5-fluorouracil (FUra) against murine and human neoplasms by increasing intracellular reduced folate concentrations. We were interested in their use in a combination to inhibit non-small cell lung cancer (NSCLC) cell growth and therefore conducted an in vitro study to investigate the cytotoxic activities of combinations of CDDP plus FUra, with and without LV (20 microM), against seven NSCLC cell lines. A tetrazolium assay with application of the classical isobole method was used to test drug combinations. We found that LV enhanced FUra but not CDDP cytotoxicity and that the degree of enhancement was negatively correlated with the effect of FUra. There was an overall additive combination effect of CDDP plus FUra, although there may be synergy at higher effect levels. There was synergy to a combination of CDDP, FUra, and LV, presumably primarily related to the synergistic effects of adding LV to FUra. In summary, LV and CDDP enhanced FUra cytotoxicity in a complementary fashion and there was clear synergy of a combination of CDDP, FUra, and LV against a panel of NSCLC cell lines. Our in vitro results provide a rationale for controlled clinical studies of this three-drug regimen in patients with NSCLC.

Carcinoma, Non-Small-Cell Lung↗