Search PubMed⌕ Search

Biomedical subjects

I S Shiah

Publications and source records attributed to I S Shiah.

25 records · Page 2Linked to original sources

Divalproex sodium attenuates growth hormone response to baclofen in healthy human males.

The effect of divalproex sodium (DVP) on gamma-aminobutyric acid-B (GABAB) receptor function in humans was assessed by measuring growth hormone (GH) responses to a challenge with a GABAB receptor agonist, baclofen, in 10 male healthy volunteers. Each subject received 20 mg of baclofen at 10:00 A.M., and blood samples were collected for measuring GH before and 30, 60, 90, 120, 150, 180 min after baclofen administration. The baclofen challenge test was repeated after 1 week of treatment with DVP (1000 mg/day). The results showed that the plasma GH response to baclofen was significantly attenuated by the DVP treatment and that the degree of attenuation was positively correlated with the blood levels of valproic acid. Our findings suggest that DVP downregulates hypothalamic GABAB receptor function in humans.

Adult↗

Cortisol, hypothermic, and behavioral responses to ipsapirone in patients with bipolar depression and normal controls.

To examine if 5-HT1A receptor function is involved in the pathophysiology of bipolar depression, we measured the cortisol, hypothermic and behavioral responses to ipsapirone, a 5-HT1A receptor agonist, in 8 patients with bipolar depression and 26 normal controls. After obtaining blood samples for baseline cortisol levels and measuring baseline body temperature, a single dose of 0.3 mg/kg of ipsapirone was administered orally to all the subjects, and further blood and temperature readings were obtained every 30 min for 3 h. The results showed that the administration of ipsapirone led to a significant increase in cortisol release and a significant decrease in body temperature both in bipolar depressed patients and normal controls. There was no significant difference in the cortisol or hypothermic responses to ipsapirone between groups. However, there was a significant positive correlation between the Hamilton Depression Rating (HAMD) scores and the hypothermic response in the depressed patients, while the HAMD scores were not significantly correlated with the cortisol response. Comparing our findings with those of previous studies, we suggest that the alterations in 5-HT1A receptor sensitivity in depressed patients may be related to the severity of depression, and they may only occur in more severely depressed patients.

Adult↗

Plasma free 3-methoxy-4-hydroxyphenylglycol predicts response to fluoxetine.

This study was designed to investigate the relationship between platelet serotonin (5-HT) and plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG) measures in depressed outpatients obtained from the same patient with unipolar depression during the pretreatment period and subsequent response to 6 weeks of treatment with either fluoxetine or maprotiline. Compared to the nonresponder group, the fluoxetine responders showed significantly higher pretreatment levels of MHPG, but no difference in pretreatment 5-HT levels. There were no significant differences in either 5-HT or MHPG levels between maprotiline responders and nonresponders. As to posttreatment levels, there were no between-group differences in 5-HT or MHPG between responders and nonresponders to either fluoxetine or maprotiline. When the relationships between changes in 5-HT or MHPG levels and treatment response were examined, 5-HT values showed a marked decrease in both fluoxetine responders and nonresponders, but no significant changes were found in the maprotiline treatment groups. On the other hand, MHPG levels in the fluoxetine nonresponders tended to increase (borderline significance), whereas the MHPG levels for fluoxetine responders and maprotiline responders and nonresponders were unaffected from pre- to posttreatment. Pretreatment levels of plasma free MHPG appear to predict response to fluoxetine.

Adult↗

Sumatriptan-induced growth hormone release in patients with major depression, mania, and normal controls.

The purpose of this study was to assess serotonergic function in patients with major depression or mania using sumatriptan, a novel 5-HT1D receptor agonist, as a pharmacological probe in a neuroendocrine challenge paradigm. We studied 18 drug free patients (10 with acute unipolar major depression and 8 with acute mania) who met DSM-IV criteria, and healthy controls. Subjects presented for testing after an overnight fast. After obtaining a blood sample for baseline growth hormone (GH) levels, sumatriptan (6 mg) was given subcutaneously, and further blood samples were collected at half hour intervals for 2 hours. The results showed that GH responses to sumatriptan were blunted in depressed patients but not in manics, compared to healthy controls. There were no differences in basal GH levels between the 3 groups. The results of this study provide further support for the role of serotonergic system in pathophysiology of major depression, but not in mania.

Adult↗

Effects of divalproex sodium on 5-HT1A receptor function in healthy human males: hypothermic, hormonal, and behavioral responses to ipsapirone.

Hypothermic and hormonal responses to a challenge with a selective 5-HT1A receptor agonist ipsapirone are considered to provide an index of 5-HT1A receptor function in humans. To examine the effects of divalproex sodium (DVP) on 5-HT1A receptor function in humans, we measured the hypothermic, adrenocorticotropic hormone (ACTH) cortisol, and behavioral responses to ipsapirone in 10 healthy male volunteers. After obtaining a blood sample for baseline hormone levels and measuring body temperature, a single dose of 0.3 mg/kg of ipsapirone was given orally to all the subjects and further bloods and temperature reading were obtained at regular intervals for three hours. The ipsapirone challenge tests were repeated after the subjects had been treated with DVP (1000 mg/day) for one week. The results showed that the hypothermia induced by ipsapirone was significantly attenuated by the DVP treatment, whereas the ACTH/cortisol release and the behavioral responses following ipsapirone challenges were not altered. Our findings suggest that DVP may enhance 5-HT neurotransmission in humans via a subsensitization of 5-HT1A autoreceptors but does not appear to affect postsynaptic 5-HT1A receptors.

Adrenocorticotropic Hormone↗

Vascular dementia of Binswanger's type: clinical, neuroradiological and 99mTc-HMPAO SPET study.

In 24 patients with vascular dementia of Binswanger's type (VDBT) and 14 age-matched neurologically normal volunteers, we investigated the relationship between clinical features, white matter lesions (leuco-araiosis) and cerebral atrophy on computed tomographic (CT) scan, and regional cerebral blood flow. All subjects underwent the Mini-Mental State Examination of Taiwan, version 1 (MMSE-T1), for assessing the severity of cognitive impairment. The patients were subdivided into two groups, one with mild to moderate (group I, MMSE-T1 scores: 11-24, n=11), and the other with severe dementia (group II, MMSE-T1 scores: below 10, n=13). White matter degeneration was evaluated with densitometric methods. Loss of brain parenchyma was estimated with seven linear measurements (Evan's ratio, third ventricle ratio, width of temporal horn tip, anterior-posterior length of temporal horn, anterior-posterior length of Sylvian fissure and width of frontal interhemispheric fissure) by CT scans. Regional cerebral blood flow was determined with technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET). In neuroimaging studies, subcortical leuco-araiosis was localized at the frontal region in group I patients and scattered diffusely in group II patients. 99mTc-HMPAO SPET analysis revealed reduction of regional cerebral blood flow in the frontal lobe in group I patients and widespread reduction of regional cerebral blood flow in group II patients. A correlation between frontal leuco-araiosis and perfusion defect of the frontal pole was demonstrated in group I patients, showing findings typical of subcortical dementia. There was no difference in frontal atrophic measurements between group I patients and controls. Ratios of volumes of lost brain parenchyma and leuco-araiosis were significantly higher in group II patients than in the age-matched controls, corresponding to a diffuse cerebral perfusion defect. These results suggest that patients with VDBT have early frontal lobe involvement with posterior progression. Patients with mild VDBT are more likely to show reduction of frontal cerebral blood flow and leuco-araiosis, while those with severe VDBT are more likely to have diffuse leuco-araiosis, cerebral hypoperfusion and brain atrophy.

Aged↗

Platelet 5-HT and plasma MHPG levels in patients with bipolar I and bipolar II depressions and normal controls.

BACKGROUND: It has been suggested that platelet serotonin (5-HT) content may reflect aspects of the presynaptic reuptake of 5-HT, while plasma 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels may provide an index of central noradrenergic function. METHODS: In order to determine if there is a biological distinction in 5-HT or noradrenergic function within bipolar I and bipolar II depressions, we measured levels of platelet 5-HT and plasma MHPG in 12 patients with bipolar I depression, 12 patients with bipolar II depression, and 20 normal healthy controls. All subjects were medication free for at least 4 weeks prior to the study. RESULTS: There was a trend towards higher platelet 5-HT in bipolar I or II depressions when compared to normal controls, whereas there was no difference in platelet 5-HT levels between bipolar I and II depressed patients. When bipolar I and II patients were pooled, there was a significant increase in platelet 5-HT levels in bipolar depressives compared to normal controls, and there was a trend towards a weak positive correlation between platelet 5-HT and 21-item HAMD scores in the patient group. In contrast, there was no difference in plasma MHPG levels between the three groups. LIMITATIONS: This study was limited to a small sample size, single point sampling and did not match seasons. CONCLUSIONS: Our findings did not provide supportive evidence for a distinctive 5-HT or noradrenergic function within bipolar I and bipolar II depressions. However, the finding of increased platelet 5-HT levels in bipolar depressed patients compared to normal controls is consistent with the results of previous studies, and may suggest an increase in presynaptic 5-HT reuptake, presumably resulting from diminished synaptic 5-HT availability in this condition.

Adult↗