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Biomedical subjects

B K Tan

Publications and source records attributed to B K Tan.

At least 73 records · Page 4Linked to original sources

Rectal carcinoma during pregnancy.

Rectal carcinoma presenting during pregnancy is rare with a reported incidence of 0.002%. Management of such an emotionally charged condition can be difficult, especially when the twin goals of curing the disease and preserving the pregnancy are divergent. Four cases of rectal carcinoma presenting during pregnancy are reported. In the first or second trimester of pregnancy, it is possible to resect the tumour with preservation of pregnancy, and in the third trimester, it is best to bring the pregnancy to term before removing the tumour. Unfortunately, the prognosis for such rectal cancer is poor.

Abortion, Spontaneous↗

The effects of tannic acid on serum and liver lipids of RAIF and RICO rats fed on high fat diet.

1. Male genetically hypercholesterolemic (RICO) and normocholesterolemic (RAIF) rats were divided into four groups and each group was fed one of the following diets for 10 weeks: a standard diet (STD); STD supplemented with tannic acid (STD + T); a high fat diet (HFD) and a high fat diet with tannic acid (HFD + T). 2. The RAIF and RICO rats when fed on HFD + T showed beneficial changes in serum lipids compared to the rats fed HFD. The lipid parameters between the groups fed STD and STD + T in both strains were unchanged. 3. The possible modes of hypocholesterolemic action of tannic acid in these rats is discussed.

Animals↗

The effects of tannic acid on serum lipid parameters and tissue lipid peroxides in the spontaneously hypertensive and Wistar Kyoto rats.

The effects of tannic acid or its vehicle (normal saline) on blood pressure, blood lipid parameters, liver and kidney malonaldehyde (MDA) levels were investigated in the spontaneously hypertensive rats (SHR) and the normotensive Wistar Kyoto rats (WKY). When tannic acid dissolved in normal saline, was injected intraperitoneally (i.p.) twice a week at a single dose of 15 mg/rat/injection (30 mg/week) for a period of 10 weeks to the SHR, the serum total cholesterol (TC), low density lipoprotein cholesterol (LDLC), and triglycerides (TG) were significantly lower compared to the vehicle-treated SHR. However, there was no significant difference in the high density lipoprotein cholesterol (HDLC) concentration. Administration (i.p.) of tannic acid to the WKY did not cause any significant effects on the serum TC, LDLC, and TG levels. The HDLC concentration of the tannic acid-treated WKY was significantly higher than in the vehicle-treated WKY. The LDLC/HDLC ratio was significantly lowered compared to their respective controls for both strains of rats. When tannic acid was administered (i.p.) by osmotic pumps over a 13 day period (30 mg tannic acid/week), the kidney MDA level in the SHR was found to be significantly lower than in the vehicle-treated SHR. The liver MDA level was not significantly different between the treated and control rats. In the WKY, MDA was detected in trace amounts in the kidneys of both the control and treated rats. There were appreciable amounts of MDA detected in the liver of the control and treated rats but these were not significantly different from one another.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

The effect of vitamin D analogs and of vitamin D-binding protein on lymphocyte proliferation.

In the absence of vitamin D-binding protein (DBP), 1,25-(OH)2D3 at 10(-12) M significantly inhibited the [3H]thymidine incorporation in human lymphocytes during mixed lymphocyte cultures (MLC) or after phyto-hemaglutinin (PHA) stimulation. In the presence of a physiological concentration of DBP (5 x 10(-6) M), the concentration of 1,25-(OH)2D3 required for inhibition was 10(-10) M (for PHA-cultures) and 10(-9) M (for MLC). Several vitamin D analogs were compared for their inhibitory action on PHA stimulation. In the absence of DBP, the concentration necessary for 50% inhibition of [3H]thymidine incorporation ranged from 10(-12) M [1,25-(OH)2D3 and 24,24-F2-1,25-(OH)2D3], over 10(-10) M [1,24R, 25-(OH)3D3; 1,25S, 26-(OH)3D3 and 26,27-F6-1,25-(OH)2D3] and 10(-8) M [25 OHD3 and 24,25-(OH)2D3] to 10(-6) M [calcitriol-lactone]. This rank order correlates with the binding affinity of the various analogs to the cytoplasmic 1,25-(OH)2D3-receptor. DBP counteracted the inhibitory effect of all analogs and the degree of counteraction was directly proportional to the binding affinity between DBP and the vitamin D analog. DBP thus decreased the in vitro inhibitory action of 1,25-(OH)2D3 and its analogs on lymphocyte proliferation. Of all analogs tested, only 1,25-(OH)2D3 had a significant effect at a physiological concentration.

Calcitriol↗

Blood pressure, plasma and pituitary prolactin levels and their responses to bromocriptine in the segregating F2 generation of the SHR/WKY hybrid.

Our previous study in the spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar-Kyoto (WKY), had shown differences in plasma and pituitary prolactin (PRL) levels as well as in their responses to bromocriptine (BRC), a centrally acting dopaminergic agonist. The results provided evidence for a central dopaminergic deficiency in the SHR and suggested a possible genetic linkage between blood pressure (BP) and PRL and their responses to BRC in the SHR. To investigate this possibility further, we have repeated the experiment, using the same protocol, in the segregating F2 generation of the SHR/WKY hybrid which was classified according to BP into low, intermediate and high BP groups. The results from this study show that the differences between BP and PRL and their responses to BRC are similarly present in the three groups of the F2 generation. They provide further evidence that suggests a genetic linkage between BP and PRL in the SHR.

Animals↗

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↗

Plasma and pituitary prolactin and blood pressure in bromocriptine-treated spontaneously hypertensive and Wistar-Kyoto rats.

1. The effects on blood pressure (BP) and plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine delivered by osmotic minipump were investigated in spontaneously hypertensive rats (SHR) and their normotensive controls, the Wistar-Kyoto rats (WKY). 2. In the SHR, a fall in BP which was steepest over the initial few days and sustained up to day 12 was observed in the bromocriptine-treated group compared with the lack of a change in BP observed in the vehicle-treated group. The plasma PRL level taken on day 13 was found to be significantly lower in the bromocriptine-treated group than in the vehicle-treated group. 3. In the WKY, bromocriptine had no significant effect on either BP or plasma PRL. 4. Pituitary PRL content was significantly lower in the SHR than in the WKY. The suppression by bromocriptine treatment was greater in the SHR than in the WKY. 5. These results provide further evidence for a central dopaminergic insufficiency in the SHR and raise the possibility that PRL may, either directly or indirectly by interacting with other factors in the SHR, influence BP.

Animals↗

Plasma tryptophan and tyrosine ratios to competing amino acids in relation to antidepressant response to citalopram and maprotiline. A preliminary study.

Pretreatment plasma ratios of tryptophan (Trp) and tyrosine (Tyr) to other large neutral amino acids were determined in 27 depressed patients who completed a double-blind trial of citalopram, a selective serotonin uptake inhibitor, against maprotiline, a selective noradrenaline uptake inhibitor. The Trp ratio and the Tyr ratio were decreased in the total patient sample as compared with healthy controls. Plasma Tyr ratio was normal in the endogenous, but significantly decreased in the non-endogenous depressives. There was no significant relationship between the plasma Trp ratio and the probenecid-induced accumulation of 5-HIAA in the CSF, or between the plasma Tyr ratio and HVA level in CSF, whereas the CSF level of MHPG correlated significantly with the plasma Tyr ratio. There was a significantly positive correlation between the Trp ratio, the Tyr ratio, their sum and the final Hamilton depression score in 14 patients treated with citalopram; on the whole, this association was evident also in the endogenous and non-endogenous subgroups. In 13 patients on maprotiline there was a significantly positive correlation between the plasma Tyr ratio and the percent reduction of Hamilton depression score; this association was poor in the endogenous, whereas a trend towards a correlation remained in the non-endogenous subgroup. The results suggest that the plasma Trp and Tyr ratios may be determinants of clinical improvement in depressed patients to treatment with citalopram and maprotiline. However, further studies are needed on larger patient samples to allow a firm conclusion.

Adult↗

Two direct (nonchromatographic) assays for 25-hydroxyvitamin D.

We describe direct, nonchromatographic assays for 25-hydroxyvitamin D3 in which we use either rat vitamin D-binding protein or rabbit antibodies to 25-hydroxyvitamin D3-3-hemisuccinate-bovine serum albumin as binding protein. Nonspecific interferences in serum could be eliminated by an appropriate extraction method or in obtaining data for the calibration curve, by using vitamin D-free human serum. The latter is prepared by affinity chromatography with use of immobilized antibodies against human vitamin D-binding protein. Values obtained by the direct assays and those obtained by two different chromatographic methods correlated well (r greater than 0.95). The direct competitive protein-binding assay overestimated the true 25-hydroxyvitamin D3 concentration by about 20%, but this percentage was constant from 5 to 600 micrograms/L. Overestimation by the direct radioimmunoassay was less than 10%. These two direct assays for 25-hydroxyvitamin D3 allow reliable, rapid, and simple screening for vitamin D deficiency or excess.

Acetates↗

The isolation and characterization of the 25-hydroxyvitamin D-binding protein from chick serum.

The binding protein for 15-hydroxyvitamin D3 (25-OH-D3) was isolated from chick serum. The molecular weight was 60,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, without the existence of sub-units. Its sedimentation coefficient was 4.3 S. The isoelectric points of the major and minor components were 6.1 and 5.9, respectively. Addition of 25-hydroxyvitamin D3 causes an anodal shift in the isoelectric point of the two forms of the binding protein. Heating at 60 degrees C slowly destroys the binding protein but the addition of vitamin D metabolites increases its thermostability. The binding protein has probably a single binding site for all vitamin D metabolites and its association constant for 25-OH-D3 at 4 degrees C and pH 7.4 is 10(9) M-1. The same affinity is found for 24,25-dihydroxyvitamin D3 but 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 have a 3- and 10-fold lower affinity, respectively. The amino acid composition is very similar to that of the human and rat binding protein. The concentration of chick 25-hydroxyvitamin D3-binding protein was higher in egg-laying hens (10 microM) than in immature hens (4 microM) or immature or adult roosters (4 microM). Chick plasma contains virtually only a 4 S form of the 25-hydroxyvitamin D3-binding protein but partially hemolyzed chick serum also contains a 6 S form. Addition of pure actin to chick plasma or serum converts all 4 S form to the 6 S form. The serum 25-hydroxyvitamin D3-binding protein is thus heterogenous since it exists in two 4 S forms (with different pI) and a 6 S form (complexed with actin). No evidence was found for the existence of a separate vitamin D3-binding protein.

Amino Acids↗

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↗