PubMed Health⌕ Search

Biomedical subjects

B K Tan

Publications and source records attributed to B K Tan.

At least 55 records · Page 3Linked to original sources
PubMed1999

Selective laser sintering: application of a rapid prototyping method in craniomaxillofacial reconstructive surgery.

Advances in technology have benefited the medical world in many ways and a new generation of computed tomography (CT) scanners and three-dimensional (3-D) model making rapid prototyping systems (RPS) have taken craniofacial surgical planning and management to new heights. With the development of new rapid prototyping systems and the improvements in CT scan technology, such as the helical scanner, biomedical modelling has improved considerably and accurate 3-D models can now be fabricated to allow surgeons to visualise and physically handle a 3-D model on which simulation surgery can be performed. The principle behind this technology is to first acquire digital data (CT scan data) which is then imported to the RPS to fabricate fine layers or cuts of the model which are gradually built up to form the 3-D models. Either liquid resin or nylon powder or special paper may be used to make these models using the various RPS available today. Selective laser sintering (SLS), which employs a CO2 laser beam to solidify special nylon powder and build up the model in layers is described in this case report, where a 23-year old Chinese female with panfacial fracture and a skull defect benefited from SLS biomodelling in the preoperative workup.

Accidents, Traffic↗
PubMed1998

Cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide in the anaesthetised rat and isolated right atria.

The cardiovascular activity of 14-deoxy-11,12-didehydroandrographolide (DDA) from Andrographis paniculata (Burm.f.) Nees (Acanthaceae) was elucidated in anaesthetised Sprague-Dawley (SD) rats and isolated rat right atria. In anaesthetised rats, DDA produced significant falls in mean arterial blood pressure (MAP) and heart rate in a dose-dependent manner with the maximum decrease of 37.6 +/- 2.6% and 18.1 +/- 4.8%, respectively. The ED50 value for MAP was 3.43 mmol kg-1. Pharmacological antagonist studies were done using this dose. The hypotensive action of DDA was not mediated through effects on the alpha-adrenoceptor, muscarinic cholinergic and histaminergic receptors, for it was not affected by phentolamine, atropine as well as pyrilamine and cimetidine. However, it seems to work via adrenoceptors, autonomic ganglia receptor and angiotensin-converting enzyme, since the hypotensive effect of DDA was negated or attenuated in the presence of propranolol, hexamethonium and captopril. In the isolated right atria, DDA caused negative chronotropic action and antagonised isoproterenol-induced positive chronotropic actions in a non-competitive and dose-dependent manner. These results further supported the bradycardia-inducing and beta-adrenoceptor antagonistic properties of DDA in vivo.

Anesthesia↗
PubMed1998

Vasorelaxation of rat thoracic aorta caused by 14-deoxyandrographolide.

1. The pharmacological effects of 14-deoxyandrographolide on rat isolated thoracic aorta were examined. 2. 14-Deoxyandrographolide (2.5-120 mumol/L) inhibited contractions induced by phenylephrine (PE; 0.1 mumol/L) and high K+ (80 mmol/L) in a concentration-dependent manner in endothelium-intact aorta. The effect was attenuated in endothelium-denuded aorta without modifying the maximal response. Like verapamil, 14-deoxyandrographolide produced a much greater vasorelaxant effect in aorta precontracted by KCl than by PE. 14-Deoxyandrographolide (20-60 mumol/L) also inhibited responses of the rat aorta to PE. 3. In Ca(2+)-free medium (KCl 55 mmol/L), 14-deoxyandrographolide (20-80 mumol/L) antagonized Ca(2+)-induced vasocontraction in a concentration-dependent manner and transient contractions induced by both caffeine (10 mmol/L) and nor-adrenaline (1 mumol/L) were suppressed or almost abolished by 14-deoxyandrographolide. 4. The vasorelaxant effect of 14-deoxyandrographolide was partially antagonized by NG-nitro-L-arginine methyl ester (25 mumol/L), a specific and competitive nitric oxide synthase (NOS) inhibitor, and methylene blue (10 mumol/L), a soluble guanylate cyclase inhibitor, but was not affected by indomethacin (20 mumol/L), a cyclo-oxygenase inhibitor, or glibenclamide (10 mumol/L), an ATP-sensitive K(+)-channel blocker. 5. These results suggest that the vasorelaxant activity of 14-deoxyandrographolide may be mediated via the activation of NOS and guanylate cyclase, as well as the blockade of Ca2+ influx through both voltage- and receptor-operated Ca2+ channels.

Animals↗
PubMed1997

Pharmacological activity of the interdomain segment between metalloproteinase and disintegrin domains.

Metalloproteinases (haemorrhagic or non-haemorrhagic), disintegrins and most probably C-type lectin-related proteins are derived by the proteolysis of a common precursor protein. There is a short interdomain segment between the metalloproteinase and disintegrin domains which will be released into the venom. To determine whether this region of the molecule contributes to the biological role of the precursors or the products derived by the proteolysis of the precursors, we synthesized a peptide based on this short segment and examined its toxicity and biological activity. The synthetic peptide did not show any lethal toxicity, anticoagulant and antiplatelet effects. However, the peptide appeared to lower the blood pressure or normotensive rats upon infusion, but did not affect the blood levels of triglyceride, total cholesterol, high-density lipoproteins or low-density lipoproteins. The peptide, however, failed to exhibit any effect on spontaneously hypertensive rats and hence may not have a potential as an antihypertensive agent. Based on these results, we conclude that this interdomain segment may not contribute significantly to the biological activity of precursor proteins.

Animals↗
PubMed1997

Mechanisms of cardiovascular activity of Andrographis paniculata in the anaesthetized rat.

The cardiovascular activities of crude water extract (WE) of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), its three semi-purified ethyl acetate (FA), n-butanol (FB) and aqueous (FC) fractions, as well as andrographolide, a major plant constituent, were elucidated in anaesthetized Sprague-Dawley (SD) rats for the very first time. FA and andrographolide, which possesses multiple pharmacological activities, elicited no drop in mean arterial blood pressure (MAP), while WE, FB and FC produced a significant fall in MAP in a dose-dependent manner without significant decrease in heart rate. The ED50 values for WE, FB and FC were 11.4, 5.0 and 8.6 mg/kg-respectively. These suggested that the hypotensive substance(s) of the crude water extract was concentrated in FB. Pharmacological antagonist studies were consequently only tested in FB (5 mg/kg). The hypotensive action of FB was not mediated through effects on the beta-adrenoceptor, muscarinic cholinergic receptor and angiotensin-converting enzyme, for it was not affected by propranolol, atropine and captapril, respectively. However, it seems to work via alpha-adrenoceptors, autonomic ganglion and histaminergic receptors, since the hypotensive effect of FB was negated or attenuated in the presence of phentolamine, hexamethonium as well as pyrilamine and cimetidine.

1-Butanol↗
PubMed1997

Differentiation induction of HL60 cells by 1,25(OH)2D3, all trans retinoic acid, rTGF-beta2 and their combinations.

1,25 Dihydroxyvitamin D3 (D3), all trans retinoic acid (atRA) and the cytokine rTGF-beta2 are growth and differentiation modulators of promyelocytic leukemia. D3 gives rise to a functional monocytic cell population whereas single atRA therapy induces granulocytic cell features. rTGF-beta2 reduces HL60 cell proliferation but has no differentiating capacity. Combination treatment demonstrates additive effects between either D3 and atRA or D3 and rTGF-beta2, resulting in a cell population with mixed characteristics since individual cells exhibit both monocytic as granulocytic cell features. The capacity of single and combined treatments to induce a permanent differentiation was investigated. Therefore, cells were preincubated with the drugs during six days, test drugs were removed and cell number was monitored. The total cell count of populations treated with single agents remains constant for only a few days and then increases rapidly. rTGF-beta2 cooperated with D3 in inducing a long-lasting differentiation state (3 weeks). Addition of atRA to this combination did not significantly alter proliferation or differentiation, but some cells underwent apoptosis. Therefore, a total and permanent differentiation of leukemic cells may be achieved by repeated exposure to a combination of differentiation inducing agents.

Antigens, Neoplasm↗
PubMed1996

In vitro cytotoxicity and immunomodulating property of Rhaphidophora korthalsii.

An in vitro cytotoxic screening of extracts of Rhaphidophora korthalsii indicated cytotoxicity in the ether fraction. ED50 values of the extract against P388, Molt 4, KB and SW 620 were 12, 14, 8 and 13 micrograms/ml, respectively. The extract was relatively more toxic on P388 and Molt 4 cell lines at concentrations of 50 micrograms/ml and 100 micrograms/ml. Screening with mouse splenocytes showed that the hot water extract had splenocytes stimulating activity.

Adenocarcinoma↗
PubMed1996

Enhancement of antiproliferative activity of 1alpha,25-dihydroxyvitamin D3 (analogs) by cytochrome P450 enzyme inhibitors is compound- and cell-type specific.

Ketoconazole (keto) or liarozole (liaro), inhibitors of the cytochrome P450 enzymes that mediate vitamin D and A hydroxylations, could potentiate the antiproliferative effects of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and its analogs. Proliferation of MCF-7 and T47-D human breast cancer cells, MG-63 human osteosarcoma cells and HL-60 human promyeloid leukemia cells was concentration dependently inhibited by 1alpha,25(OH)2D3. The vitamin D analogs KH 1060 [20-epi-22-oxa-24,26,27-trihomo-1alpha,25(OH)2D3], RO 23-6010 [16-ene-23-yne-26-trifluoro-1,25(OH)2D2D3], ZXY 835 [20-epi-23-yne-25,26-epoxy-1alpha(OH)D3], and CD 99 [11alpha-methyl-1alpha,25(OH)2D3] were 150-,58-,16- and 7-fold more potent than 1alpha,25(OH)2D3 in inhibiting the proliferation of MCF-7 cells, respectively. A similar rank order of potency was observed in other cell lines. The antiproliferative effects of the vitamin D hormone and analogs was enhanced in MCF-7 cells when coincubated with 1 microM keto (7-, 10-, 5-, 25- and 1.3-fold more potent than in the absence of keto), respectively. The antiproliferative effect was less enhanced when 1alpha,25(OH)2D3 or its analogs KH 1060, ZXY 835 and RO 23-6010 were combined with liaro (3-, 7-, 2- and 3-fold, respectively). Keto and liaro did not markedly potentiate the activity of 1alpha,25(OH)2D3 or its analogs in MG-63 or HL-60 cells. These results suggest that differences in cellular metabolism can at least partially explain the different potency of vitamin D analogs. Moreover, the metabolism of vitamin D analogs is cell-type specific.

Calcitriol↗
PubMed1996

Hypotensive activity of aqueous extract of Andrographis paniculata in rats.

1. The hypotensive activity of an aqueous extract of Andrographis paniculata was studied using chronic intraperitoneal (i.p.) infusions by osmotic pumps. The extract exhibited a dose-dependent hypotensive effect on the systolic blood pressure (SBP) of spontaneously hypertensive rats (SHR). 2. The optimum hypotensive dose determined was repeated in a study in SHR and their normotensive controls, Wistar-Kyoto (WKY) rats, to demonstrate its comparative effects on the SBP, plasma and lung angiotensin-converting enzyme (ACE) activities, as well as on lipid peroxidation in the kidneys, as measured by the thiobarbituric acid (TBA) assay. 3. The extract significantly lowered the SBP of both SHR and WKY rats. 4. Plasma, but not lung, ACE activity and kidney TBA level were significantly lower in extract-treated SHR when compared with vehicle-treated SHR controls. 5. Plasma and lung ACE activities as well as kidney TBA levels were not significantly different between extract- and vehicle-treated WKY rats. 6. This study indicates that the aqueous extract of A. paniculata lowers SBP in the SHR possibly by reducing circulating ACE in the plasma as well as by reducing free radical levels in the kidneys. The mechanism(s) of hypotensive action seems to be different in WKY rats.

Analysis of Variance↗
PubMed1996

Effects of celery extract and 3-N-butylphthalide on lipid levels in genetically hypercholesterolaemic (RICO) rats.

1. Aqueous celery extract was administered intraperitoneally to genetically hypercholesterolaemic (RICO) and normocholesterolaemic (RAIF) rats via Alzet osmotic pumps over a 13 day period. 2. The serum cholesterol concentration of the celery extract-treated RICO rats was found to be significantly lower (P < 0.05) than the control rats. Aqueous celery extract was effective in preventing the rise of cholesterol level in the RICO rats. However, no such observation was seen in the RAIF rats. The serum triglyceride level was unchanged in both strains of rats. 3. When 3-n-butylphthalide (BuPh), a unique component in celery, was administered in the same manner to the RICO and RAIF rats, it did not produce significant changes in the serum and liver lipid profiles of these rats. The activities of hepatic 3-hydroxy-3-methylglutaryl CoA reductase in both strains of rats were also not significantly different from their respective controls. 4. Together with our recently reported thin-layer chromatography findings that BuPh was not detected in the aqueous celery extract, this study suggests that the effect of celery extract on serum cholesterol levels in the RICO rats could be attributed to chemical constituents other than BuPh.

Animals↗
PubMed1996

Nonhypercalcemic vitamin D analogs: interactions with the vitamin D-binding protein.

The natural vitamin D hormone, 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3), not only regulates serum and bone calcium homeostasis but is probably also a paracrine factor in several cells and tissues including skin, immune system, placenta and brain, where it stimulates cell differentiation and inhibits cell proliferation. Several structural analogs of 1 alpha, 25-(OH)2D3 not only have superagonist activity but also display a selective action profile: indeed they maintain or have increased activity on cell differentiation/proliferation but also have substantially decreased calcemic activity when compared to 1 alpha,25-(OH)2D3. This decreased calcemic activity is partially due to mere pharmacological reasons: because of low binding affinity for the plasma vitamin D-binding protein, a more rapid extracellular metabolism and increased cellular uptake is possible when compared to 1 alpha,25-(OH)2D3. Their short extracellular half-life combined with comparable or enhanced transactivation potency together with analog-and cell-type-specific intracellular metabolism can probably explain why some analogs have a unique combination of superagonist activity and specific action profile with favorable dissociation of differentiation versus calcemic potency.

Animals↗
PubMed1995

Antagonistic activity of 24-oxa-analogs of vitamin D.

24-Oxa-vitamin D3 (24-oxa-D3) and 24-oxa-1 alpha-hydroxyvitamin D3 were designed as possible inhibitors of the vitamin D metabolic activation pathway. Their affinity for the vitamin D receptor (from pig intestine) and human vitamin binding protein were reduced, and their potency to induce cell differentiation of human leukemia cells (HL 60) or osteosarcoma cells (MG 63) was markedly reduced (19% and 3%, respectively), in comparison with calcitriol. A single or chronic injection of 24-oxa-D3 had no biological activity, whereas chronic administration of 24-oxa-1 alpha-hydroxy-D3 showed weak agonist activity in rachitic chicks. When the 24-oxa-D3 was given prior to a single injection of vitamin D3, lower values of serum calcium (64% of the value obtained in vitamin D-treated animals), osteocalcin (52%), 25-(OH)D3 (45%) and duodenal calbindin-D 28K (9.4%) were found. When given chronically in a 100-fold more excess no clear antagonistic effects were observed. 24-Oxa-D3 is thus a new metabolic weak antagonist of vitamin D3, but adding a hydroxyl group at C-1 creates a weak agonist.

Animals↗
PubMed1995

Differentiation induction of human leukemia cells (HL60) by a combination of 1,25-dihydroxyvitamin D3 and retinoic acid (all trans or 9-cis).

1,25(OH)2D3 and two stereoisomers of retinoic acid, all trans and 9-cis retinoic acid, are regulators of cell proliferation and differentiation. The aim of this study was to evaluate the effects of a combination of 1,25(OH)2D3 and retinoic acid (all trans or 9-cis) on proliferation and cell differentiation of the human promyelocytic leukemia cell line HL60, and to test the reversibility of the induced differentiation. Cell proliferation was inhibited as expected by 1,25(OH)2D3 and all trans retinoic acid alone (IC50 of cell survival was 4 x 10(-7) M, 9 x 10(-6) M and 9 x 10(-7) M for 1,25(OH)2D3, all trans and 9-cis retinoic acid, respectively). Combination of 1,25(OH)2D3 and either form of retinoic acid resulted in a partially additive decrease in cell proliferation. 1,25(OH)2D3 induced a monocytic differentiation (100% CD14+ cells with 10(-7) M 1,25(OH)2D3), while retinoic acid led to a predominantly granulocytic differentiation (36 and 42% CD67+ cells with 10(-6) M all trans and 9-cis retinoic acid, respectively). Additive effects on differentiation were observed upon combination of subtherapeutical doses of the drugs, achieving a mainly monocytic population, demonstrating the dominant role of 1,25(OH)2D3 in determining the direction of differentiation. The effects on proliferation and differentiation of the solitary drugs were reversible, while the proliferation arrest and differentiation induced by the combination persisted and even progressed after withdrawal of the drugs. We conclude that 1,25(OH)2D3 and retinoic acid (all trans or 9-cis) exert additive effects on inhibition of proliferation and induction of cell differentiation of HL60 cells, leading to a persistent differentiation, even after drug withdrawal.

Antigens, CD↗
PubMed1995

Acute zinc administration prolongs hexobarbitone-induced sleeping time in C57/6J mice.

Two experiments were carried out in this study to demonstrate the effects of acute intraperitoneal (i.p.) administration of zinc chloride (ZnCl2) on hexobarbitone-induced sleeping time (HST) in female C57/6J mice. Serum and hepatic zinc content as well as hepatic cytochrome P450 content were also estimated in ZnCl2-treated and control mice. The ZnCl2 dose used was equal to the LD50 for chronic treatment (which was 28 micrograms g-1 body weight for mice given i.p. ZnCl2 five times a week for 3 weeks), determined in an earlier experiment. ZnCl2 injections at this dose were either given singly (in experiment I) or repeated on two mornings (in experiment II). Hexobarbitone, an ultra-short-acting experimental barbiturate, was given intraperitoneally 30 min after the single ZnCl2 injection in experiment I and 24 h after the second ZnCl2 injection in experiment II. Appropriate controls were given i.p. normal saline in each experiment. The HST was observed for all the animals, using the time-points at which the loss and regain of righting reflex occurred as the parameters. The animals were later killed; their blood and livers were obtained for estimation of zinc levels and cytochrome P450 content. The results of both experiments showed that ZnCl2 had caused a significant prolongation of the HST in C57/6J mice. Serum and hepatic zinc content were also elevated in both groups of ZnCl2-treated mice compared to their respective controls. The cytochrome P450 content in the single-dose ZnCl2-treated mice was unchanged while it was significantly reduced in the double-dose ZnCl2-treated mice when compared to the content in their respective controls. These findings suggest that acute zinc excess has an inhibitory effect on the function as well as the synthesis of hepatic cytochrome P450 enzymes.

Animals↗
PubMed1995

Effects of aqueous celery (Apium graveolens) extract on lipid parameters of rats fed a high fat diet.

The antihyperlipidemic property of aqueous celery extract was studied in rats. Two groups of Wistar rats were fed a high fat diet for eight weeks to induce hyperlipidemia. One group was supplemented with aqueous celery extract in the diet while the other group served as control. At the end of the experiment, a significant reduction was found in the serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and triglyceride (TG) concentrations in the celery-treated rats. However, the concentration of hepatic TG was significantly higher in the celery-treated group than in the control group. Hepatic triacylglycerol lipase (HL) activity was found to be significantly lower in the celery-treated rats while the reverse was observed for the hepatic microsomal P450 content. Analysis of an ethereal extract of the aqueous extract of celery by thin layer chromatography (TLC) with two different solvent systems showed that the extract did not contain 3-n-butylphthalide (BuPh), a unique compound in celery that has previously been reported to have lipid-lowering action. Our study indicates that other active principle(s) could be responsible for the observed effects of aqueous celery extract on serum and hepatic lipid levels.

Animals↗
PubMed1995

Colorectal cancer in the young adult.

Out of 964 patients presenting with primary colorectal cancer (CRC) to the Department of Colorectal Surgery, Singapore General Hospital between April 1989 until December 1992, there were 57 (5.9%) aged 40 years or less. These younger patients were significantly more likely to have a family history of cancer, particularly CRC; a tumour situated more proximally; and tumours displaying certain characteristics histopathologic features. There were no adverse findings for clinicopathologic staging at presentation, curative resection rate, and systemic recurrence rate within the early follow up period. With proper management, the young adult with CRC enjoys the same outlook as his older counterpart. But, in view of the likely operation of inherited genetic factors, follow up surveillance of the patient and the provision of advice and screening are vital elements in optimising outcome. Furthermore, advice and screening should be available for first degree relatives as well.

Adult↗
PubMed1994

The biological activity of 23-oxa-, 23-oxa-24-oxo-, and 23-thia-dihydroxyvitamin D3.

Three analogs of 1 alpha,25-(OH)2D3 with an oxygen or another heteroatom at position 23 were synthesized in search of separating the cell-differentiating from the calcemic effects of the vitamin D hormone. Their ability to induce superoxide production in human myeloid leukemia cells (HL-60) was 1 alpha,25-(OH)2D3 > 23-oxa-24-oxo-1 alpha,25-(OH)2D3 > 23-thia-1 alpha,25-(OH)2D3 > 23-oxa-1 alpha, 25-(OH)2D3. 23-oxa-24-oxo-1 alpha, 25(OH)2D3 was slightly more potent than 1 alpha,25-(OH)2D3 in inhibiting cell proliferation in MCF-7 cells and 23-thia- and 23-oxa-1 alpha,25(OH)2D3 were less potent. Their in vitro potency to produce osteocalcin in MG-63 cells was 1 alpha,25-(OH)2D3 > 23-oxa-24-oxo-1 alpha,25-(OH)2D3 > 23-thia-1 alpha,25-(OH)2D3 = 23-oxa-1 alpha,25-(OH)2D3. All three analogs had reduced receptor and DBP affinity compared to 1 alpha,25-(OH)2D3. When these analogs were injected in rachitic chicks, only little calcemic effects were observed. The introduction of a heteroatom in carbon 23 of 1 alpha,25-(OH)2D3 thus creates analogs with dissociated action on cell differentiation and calcium homeostasis.

Animals↗