Biomedical subjects

B K Tan

Publications and source records attributed to B K Tan.

10 recordsLinked to original sources

PubMed1992

Structure function analysis of vitamin D analogs with C-ring modifications.

Analogs of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) with substitutions on C-11 were synthesized. Small apolar substitutions (11 alpha-methyl, 11 alpha-fluoromethyl) did not markedly decrease the affinity for the vitamin D receptor, but larger (11 alpha-chloromethyl or 11 alpha- or 11 beta-phenyl) or more polar substitutions (11 alpha-hydroxymethyl, 11 alpha-(2-hydroxyethyl] decreased the affinity to less than 5% of that of 1 alpha,25-OH)2D3. Their affinity for the vitamin D-binding protein, however, increased up to 4-fold. The biological activity of 11 alpha-methyl-1 alpha,25-(OH)2D3 closely resembled that of the natural hormone on normal and leukemic cell proliferation and bone resorption, whereas its in vivo effect on calcium metabolism of the rachitic chick was about 50% of that of 1 alpha,25-(OH)2D3. The 11 beta-methyl analog had a greater than 10-fold lower activity. The differentiating effects of the other C-11 analogs on human promyeloid leukemia cells (HL-60) agreed well with their bone-resorbing activity and receptor affinity, but they demonstrated lower calcemic effects in vivo. Large or polar substitutions on C-11 of 1 alpha,25-(OH)2D3 thus impair the binding of the vitamin D receptor but increase the affinity to vitamin D-binding protein. The effects of many C-11-substituted 1 alpha,25-(OH)2D3 analogs on HL-60 cell differentiation exceeded their activity on calcium metabolism.

Animals↗

PubMed1992

Effects of polyphenolic natural products on the lipid profiles of rats fed high fat diets.

Male Wistar rats were fed a high fat diet (HFD) containing 2.5% cholesterol and 16% lard supplemented with polyphenolic natural products namely quercetin, morin or tannic acid (100 mg/rat/day) for 4, 7 and 10 wk. Rats fed HFD without the supplements served as control. The effects of these compounds on blood lipid profiles, enzymes, liver fat and aorta of the rat were studied. In rats fed HFD containing tannic acid, plasma total cholesterol (TC), low density lipoprotein cholesterol (LDLC) and triglyceride (TG) were reduced by 33.3%, 29.6% and 65.1%, respectively, at week 10. High density lipoprotein cholesterol (HDLC) concentration was not altered. Fat deposition was also decreased in the liver of these rats. Morin significantly reduced plasma TG (65.1%) and liver fat only at week 7 while at week 10 it reduced plasma TC and LDLC by 30.9% and 29.3% respectively. The plasma HDLC concentration was increased by 47.3% at week 4 but no effect was seen at weeks 7 and 10. In the rats fed HFD containing quercetin, plasma HDLC was increased by 28.6% at week 7 but at week 10, plasma LDLC was increased by 21.2%. Quercetin did not cause any significant changes on the plasma TC, TG and liver fat at weeks 4, 7 and 10. Plasma alanine aminotransferase, alkaline phosphatase and bilirubin in control and treated groups were not significantly different. However, hepatic lipase activity in rats fed tannic acid was significantly lower. Aortae of all groups of rats showed no abnormalities. The present report indicates that tannic acid and morin are effective in reducing plasma and liver lipids when supplemented with a high fat diet in rats.

Animals↗

PubMed1991

Vitamin D analogs with low affinity for the vitamin D binding protein: enhanced in vitro and decreased in vivo activity.

The affinity of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] and analogs with side-chain modifications [MC 903 or calcipotriol, MC 1147 or 24,24-dihomo-1 alpha,25-(OH)2D3 and 1,25-(OH)2-16ene-23yne-D3] for the vitamin D receptor and the serum vitamin D binding protein (DBP) were compared. The affinity of MC 903 for the receptor from chick and rat duodenum or from human peripheral blood mononuclear cells or HL-60 cells varied between 60 and 100% relative to the affinity of 1,25-(OH)2D3. The relative affinity of 1,25-(OH)2-16ene-23yne-D3 and MC 1147 varied for the same receptors between 45-70 and 3.5-25%, respectively. The relative affinity of MC 903 for human DBP was 30-fold decreased, whereas the two other analogs did not bind to DBP at all even in more than 1000-fold excess. The in vitro biologic activity of 1 alpha,25-(OH)2D3 on phytohemagglutinin-stimulated normal human lymphocyte proliferation was markedly inhibited by the addition of physiologic amounts of DBP to the cell culture medium. No such inhibition was observed when MC 903 or 1147 was evaluated similarly. DBP therefore reversed the rank order of the in vitro potency of these analogs. Intramuscular injections for 10 consecutive days to vitamin D-deficient chicks demonstrated a greater than or equal to 100-fold lower biologic activity of MC 903, MC 1147, and 1,25-(OH)2-16ene-23yne-D3 compared to that of 1 alpha,25-(OH)2D3 as evaluated by serum calcium and osteocalcin concentrations, as well as by duodenal calbindin D28K and bone calcium content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Changes in saline and water intakes in bromocriptine-treated genetically hypertensive and normotensive rats.

1. We have previously reported on the effects of a 13-day intraperitoneal infusion of bromocriptine delivered by osmotic pump on blood pressure, plasma and pituitary PRL levels in genetically hypertensive (GH) rats and their normotensive (NT) controls. This paper reports further on that study in describing the changes in saline and water intakes in rats as a result of bromocriptine (BRC) treatment. 2. In the GH rats, bromocriptine did not have any significant effect on saline or water intake. 3. In the NT rats, bromocriptine significantly decreased saline intake and increased water intake. 4. The saline intake in the vehicle-treated GH rats was significantly lower than that in the vehicle-treated NT rats while the water intake was not significantly different. 5. These results indicate that differences exist between the GH and NT rats with regard to their saline and water intakes and their responses to chronic bromocriptine treatment. The changes in saline and water intakes in the GH rats seem to be different from those seen in the spontaneously hypertensive rat in another study.

Animals↗

PubMed1990

Plasma and pituitary thyroid-stimulating hormone levels in bromocriptine-treated New Zealand genetically hypertensive and normotensive rats.

1. The effects of a 13-day intraperitoneal (i.p.) infusion of bromocriptine, delivered by osmotic pump, on plasma and pituitary thyroid-stimulating hormone (TSH) levels were investigated in New Zealand genetically hypertensive (GH) rats and their normotensive (NT) controls. 2. In both the GH and NT rats, bromocriptine significantly reduced plasma TSH level but did not have any significant effect on pituitary TSH content. 3. No significant difference was found in the plasma TSH level and pituitary TSH content between the vehicle-treated GH and NT rats. 4. These results suggest that there are no differences between the GH and NT rats with regard to the activity of the central dopaminergic system influencing TSH release and also that TSH does not play a role in the hypertension of the GH rats.

Animals↗

PubMed1990

Plasma and pituitary thyroid-stimulating hormone and their responses to bromocriptine in the Japanese strains of hypertensive and normotensive rats and the F2 generation of the hybrid.

Plasma thyroid-stimulating hormone (TSH) concentration and pituitary TSH content were examined in bromocriptine (BRC)- and vehicle-treated male Spontaneously Hypertensive Rat (SHR), its normotensive control, the Wistar-Kyoto (WKY) rat and the F2 generation of the SHR/WKY hybrid. The hybrid rats were divided into three groups according to their systolic blood pressures (BP) as follows--group I: BP less than 140 mmHg; group II: BP = 140-160 mmHg and group III: BP greater than 160 mmHg. Plasma TSH concentrations were not significantly different between the vehicle-treated SHR and WKY nor between the three groups of vehicle-treated hybrid rats. The pituitary TSH content was significantly higher in the vehicle-treated SHR than in the vehicle-treated WKY while it was not significantly different between the three groups of vehicle-treated hybrid rats. Plasma TSH concentrations in the BRC-treated SHR, WKY and three groups of hybrid rats were significantly lower than the concentrations in the corresponding vehicle-treated rats. Pituitary TSH content were significantly lower in the BRC-treated SHR, group I and group III rats but not in the BRC-treated WKY and group II rats when compared to their respective vehicle-treated controls. The results of this study suggest that TSH is not involved in the maintenance of systolic BP in the SHR, WKY and hybrid rats.

Analysis of Variance↗

PubMed1989

Blood pressure, plasma and pituitary prolactin responses to bromocriptine in New Zealand genetically hypertensive and normotensive rats.

1. The effects on blood pressure (BP), plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine (BRC) delivered by osmotic minipump were investigated in genetically hypertensive rats (GHR) and their normotensive (NT) controls. 2. In the GHR, the mean BP in the BRC-treated group over the 13 day period of study was significantly lower than in the vehicle-treated group. In the NT rats, the mean BP in the BRC-treated group over the 13 day period was also significantly lower than in the vehicle-treated group. 3. Mean plasma PRL concentration in the GHR and NT rats were comparable. In the GHR, the mean plasma PRL concentration taken on day 13 was significantly lower in the BRC-treated group than in the vehicle-treated group. In the NT rats, the mean plasma PRL concentration taken on day 13 in the BRC-treated group was, however, not significantly different from that in the vehicle-treated group. 4. The mean pituitary PRL content was not significantly different in the GH and NT rats. There was a greater suppression of pituitary PRL content in the BRC-treated GHR than in the BRC-treated NT rats compared with their respective vehicle-treated groups. 5. The results raise the possibility that PRL may have an indirect role in the pathogenesis of the hypertension of the GHR.

Animals↗

PubMed1987

A double-blind comparative clinical trial of citalopram vs maprotiline in hospitalized depressed patients.

In a double-blind clinical trial comprising 29 depressed patients citalopram, a highly selective 5-HT re-uptake inhibitor and maprotiline, a specific NA re-uptake inhibitor, were compared. Allowing for the small sample and taking into consideration that both groups consisted of severely ill, hospitalized patients, it is notable that half of them appeared to respond to treatment. Comparison of the clinical efficacy of the two drugs showed no significant difference, but the profiles of the side-effects appeared to be different. The patients treated with citalopram showed increased sweating, drowsiness, restlessness and headache. These side-effects were almost entirely reported by the non-responders. The maprotiline patients had anticholinergic symptoms, such as dryness of mouth and constipation, side-effects which were also reported by the responders. No correlation was found between plasma steady-state levels of either drug and clinical outcome. The Dexamethasone Suppression Test (DST) appeared to show some predictive value as regards treatment response. There was a tendency towards better overall treatment results in the non-suppressor group. Determination of post-probenecid 5-HIAA, HVA and MHPG concentrations in lumbar-CSF was made in 22 patients. There was a significant negative correlation between HVA and the severity of depression, as well as a significant negative correlation of MHPG with the Newcastle score. The 5-HIAA concentration was found to be correlated with HVA, but not with MHPG. Rather surprisingly significant negative correlation between 5-HIAA and treatment results with maprotiline was found, but no correlation with MHPG. The lumbar-CSF MHPG and HVA values did not appear to have any predictive value as regards treatment response to citalopram or maprotiline. As expected the serotonin (5-HT) concentration in blood and thrombocytes in patients treated with citalopram showed a highly significant reduction after 2 and 4 weeks of treatment.

Adult↗

PubMed1976

Sodium valproate in Huntington's chorea.

In a single-case study of Huntington's Chorea the effect of sodium valproate on motor behaviour was first compared with that of L-Dopa and than investigated further alone. Drug effect was assessed in terms of number of EMG-bursts with concurrent determinations of serum-levels of sodium valproate. The main result of this study was the development of a state of tolerance to sodium valproate.

Clinical Trials as Topic↗

PubMed1976

Huntington's chorea. A random process.

The purpose of the present study was to investigate statistically the irregular nature of the choreatic jerks in Huntington's Chorea. EMG-bursts of certain muscles in a patient with Huntington's Chorea were taken as a measure of the jerks. Statistical analysis of the measurements, i.e. durations of bursts and intervals between bursts, revealed that the irregular nature of the choreatic jerks originate from a random process. Each choreatic jerk appears to be an entirely independent and unpredictable event.

Buttocks↗