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Biomedical subjects

W L Tan

Publications and source records attributed to W L Tan.

13 recordsLinked to original sources
PubMed2005

Modeling Caco-2 permeability of drugs using immobilized artificial membrane chromatography and physicochemical descriptors.

This study evaluates the potential of immobilized artificial membrane (IAM) chromatography, in combination with other physicochemical descriptors for high-throughput absorption profiling during lead optimization. An IAM chromatographic method was developed and validated. Absorption profiles of 32 structurally diverse compounds (acidic, basic, neutral and amphoteric) were then evaluated based on their IAM retention factor (log k'IAM), molecular weight (MW), calculated log P (C log P), polar surface area (PSA), hydrogen bonding capacity (HBD and HBA) and calculated Caco-2 permeability (QPCaco). Using regression and stepwise regression analysis, experimental Caco-2 permeability was correlated against log k'IAM and a combination of various physicochemical variables for quantitative structural-permeability relationship (QSPR) study. For the 32 structurally diverse compounds, log k'IAM correlated poorly with Caco-2 permeability values (R2 = 0.227). Stepwise regression analysis confirmed that Clog, PSA, HBD and HBA parameters are not statistically significant and can be eliminated. Correlation between Caco-2 cell uptake and log k'IAM was enhanced when molecular size factor (MW) was included (R2 = 0.555). The exclusion of 11 compounds (paracellularly and actively transported, Pgp substrates and blocker, and molecules with MW lesser than 200 and greater than 800) improved the correlation between Caco-2 permeability, IAM and MW factors to R2 value of 0.84. The results showed that IAM chromatography can only profile the passive absorption of drug molecules. Finally, it was confirmed in this study that the IAM model can accurately identify the Caco-2 permeability of nontransported Pgp substrates, such as verapamil and ketoconazole, through passive permeation because of their high permeability. IAM chromatography, combined with molecular size factor (MW), is useful for elucidating biopartitioning mechanism of drugs.

Caco-2 Cells↗
PubMed2001

Can dietary factors explain differences in serum cholesterol profiles among different ethnic groups (Chinese, Malays and Indians) in Singapore?

In Singapore. there exists differences in risk factors for coronary heart disease among the three main ethnic groups: Chinese, Malays and Indians. This study aimed to investigate if differences in dietary intakes of fat, types of fat, cholesterol, fruits, vegetables and grain foods could explain the differences in serum cholesterol levels between the ethnic groups. A total of 2408 adult subjects (61.0% Chinese, 21.4% Malays and 17.6% Indians) were selected systematically from the subjects who took part in the National Health Survey in 1998. The design of the study was based on a cross-sectional study. A food frequency questionnaire was used to assess intakes of energy, total fat, saturated fat, polyunsaturated fat, monounsaturated fat, cholesterol, fruits, vegetables and cereal-based foods. The Hegsted score was calculated. Serum total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol were analysed and the ratio of total cholesterol to high density lipoprotein cholesterol was computed. The results showed that on a group level (six sex-ethnic groups), Hegsted score, dietary intakes of fat, satutrated fat, cholesterol, vegetables and grain foods were found to be correlated to serum cholesterol levels. However, selected dietary factors did not explain the differences in serum cholesterol levels between ethnic groups when multivariate regression analysis was performed, with adjustment for age, body mass index, waist-hip ratio, cigarette smoking, occupation, education level and physical activity level. This cross-sectional study shows that while selected dietary factors are correlated to serum cholesterol at a group level, they do not explain the differences in serum cholesterol levels between ethnic groups independently of age, obesity, occupation, educational level and other lifestyle risk factors.

Adult↗
PubMed2001

Isolation and characterization of mutants defective in seed coat mucilage secretory cell development in Arabidopsis.

In Arabidopsis, fertilization induces the epidermal cells of the outer ovule integument to differentiate into a specialized seed coat cell type producing extracellular pectinaceous mucilage and a volcano-shaped secondary cell wall. Differentiation involves a regulated series of cytological events including growth, cytoplasmic rearrangement, mucilage synthesis, and secondary cell wall production. We have tested the potential of Arabidopsis seed coat epidermal cells as a model system for the genetic analysis of these processes. A screen for mutants defective in seed mucilage identified five novel genes (MUCILAGE-MODIFIED [MUM]1-5). The seed coat development of these mutants, and that of three previously identified ones (TRANSPARENT TESTA GLABRA1, GLABRA2, and APETALA2) were characterized. Our results show that the genes identified define several events in seed coat differentiation. Although APETALA2 is needed for differentiation of both outer layers of the seed coat, TRANSPARENT TESTA GLABRA1, GLABRA2, and MUM4 are required for complete mucilage synthesis and cytoplasmic rearrangement. MUM3 and MUM5 may be involved in the regulation of mucilage composition, whereas MUM1 and MUM2 appear to play novel roles in post-synthesis cell wall modifications necessary for mucilage extrusion.

Arabidopsis↗
PubMed1998

Malaria requiring intensive care.

We studied 24 consecutive adult patients with malaria who required intensive care between 1 January 1994 and 31 December 1997. This was out of a total of 256 patients hospitalised at the Singapore General Hospital with malaria during these 4 years. Our aim was to characterise the type and severity, clinical features, complications, treatment and outcome of adult patients with malaria who required intensive care. In addition, we compared the actual and predicted mortality based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The travel history, prophylaxis, duration of fever before receiving treatment, type of malaria and severity, clinical data, complications, APACHE II score, treatment and outcome were analysed. Most cases were imported by locals travelling overseas or foreigners infected with the parasite elsewhere. Four patients had vivax malaria and 20 patients had severe falciparum malaria. All but 1 patient received transfusion with blood products and 6 patients with severe falciparum malaria had exchange transfusions. Complications were restricted to infection with P. falciparum: 9 patients required acute dialysis and 8 required mechanical ventilation. Three patients died giving a mortality of 15% for severe falciparum malaria. The overall mortality of patients with malaria was 1.2%. The mortality of patients with malaria requiring intensive care was 12.5% as compared with a predicted mortality of 18.7% based on the APACHE II prognostication system.

APACHE↗
PubMed1995

[Multiple pulmonary embolisms in nursing home patients recognizable by alertness to certain aspecific symptoms].

OBJECTIVE: To determine whether increased alertness regarding multiple pulmonary embolism in geriatric patients increases the number of cases diagnosed. DESIGN: Retrospective descriptive study. SETTING: Dutch nursing homes Mariënhaven (psychogeriatric) in Warmond and De Wilbert (somatic and psychogeriatric) in Katwijk aan den Rijn, the Netherlands. METHOD: In the period 1989-1991, the diagnosis of multiple pulmonary embolism was suspected in 15 patients with an 'unclear' or 'aspecific' complex of symptoms, who subsequently underwent ventilation perfusion scintigraphy. RESULTS: In 11/15 patients the diagnosis of multiple pulmonary embolism was confirmed. These patients were treated with anticoagulants resulting in complete recovery in 9 patients. Aspecific symptoms suggestive of pulmonary embolism include subfebrile temperature, respiratory and sensory disturbances and a clinical picture mimicking airway infection. If lung scintigraphy is only performed if a positive diagnosis will have the therapeutical consequences for the patients concerned, and assuming that refraining from treatment would lead to death, it was calculated that on a yearly basis mortality in subjects in nursing homes could be reduced by more than 2% when appropriate diagnosis is made and treatment given. Comparison of the data from SIG Health Information (Utrecht) with the present results suggests that the prevalence of (multiple) pulmonary embolism in the Dutch nursing homes is insufficiently recognized. CONCLUSION: More alertness regarding multiple pulmonary embolism in nursing home patients will establish the diagnosis more frequently and proper treatment of this condition will lead to a decrease in mortality.

Aged↗
PubMed1995

Distortion in TGF beta 1 peptide immunolocalization in biliary atresia: comparison with the normal pattern in the developing human intrahepatic bile duct system.

Biliary atresia is an important cause of neonatal obstructive jaundice in which there is inflammation, sclerosis and eventual obliteration of the bile duct system. Its onset may be antenatal, affecting the normal development of the biliary system. The intrahepatic biliary system is derived from the ductal plate, a sheath of cuboidal epithelium that appears at the hepatocyte-mesenchymal junction around the portal vein branches at 6 weeks gestation. This epithelial structure is moulded into a network of tubular bile ducts by the proliferating mesenchyme. Certain portions of the ductal plate are selected to become definitive bile ducts, while redundant biliary epithelium is deleted. The molecular dynamics controlling the intra-uterine development of the biliary system in humans are not yet clearly understood. Transforming growth factor-beta 1 is a cytokine that stimulates mesenchymal proliferation and inhibits epithelial growth, and has been shown to be important in organogenesis. In the present study, the pattern of TGF beta 1 peptide immunolocalization was investigated with the aid of computerized image analysis, in normal human bile duct development and in biliary atresia. TGF beta 1 peptide was detected within hepatocytes and ductal plate epithelium from 7 weeks gestation; increased TGF beta 1 immunoreactivity was present within the epithelium of developing bile ducts at 13 weeks gestation, and apical polarization of the cytokine was observed from 16 weeks gestation. In biliary atresia, the TGF beta 1 immunoreactivity pattern within the bile duct structures at the porta hepatis and within intrahepatic portal tracts resembled that of the primitive ductal plate, and there was no significant apical polarization. This may indicate a developmental arrest in the normal ductal plate remodelling process in biliary atresia, and suggests an underlying epithelial-mesenchymal interactive disorder.

Adolescent↗
PubMed1988

The in vitro and in vivo antimalarial activity of some Mannich bases derived from 4-[7'-bromo (and chloro)-1',5'-naphthyridin-4'-ylamino]phenol and 4-(7'-trifluoromethylquinolin-4'-ylamino)phenol.

A series of di-Mannich bases derived from 4-[7'-bromo (and chloro)-1',5'-naphthyridin-4'-ylamino]phenol and 4-(7'-trifluoromethylquinolin-4'-ylamino)phenol were assayed for activity against chloroquine-sensitive and chloroquine-resistant isolates of cultured Plasmodium falciparum using the inhibition of uptake of radiolabelled hypoxanthine. A number of the 4-(7'-trifluoromethylquinolinyl-amino)phenols showed statistically superior activity to chloroquine and amodiaquine against both isolates. Analysis of the antimalarial activity of some of these compounds against Plasmodium berghei in mice following oral administration again demonstrated activity equal or superior to that of the established antimalarials against a chloroquine-sensitive strain, and in some cases appreciably superior activity against a chloroquine-resistant strain.

Amines↗
PubMed1987

Antimalarial activity of Mannich bases derived from 4-(7'-bromo-1',5'-naphthyridin-4'-ylamino)phenol and 4-(7'-trifluoromethylquinolin-4'-ylamino)phenol against Plasmodium falciparum in vitro.

Mono- and di-Mannich bases derived from 4-(7'-bromo-1',5'-naphthyridin-4'-ylamino)phenol and 4-(7'-trifluoromethylquinolin-4'-ylamino)phenol were assayed for antimalarial activity (using an in vitro radioisotopic technique) against two isolates of Plasmodium falciparum. Many from these two series of compounds had an IC50 value (concentration of compound causing 50% inhibition of 3H-hypoxanthine incorporation) comparable to or better than those of mefloquine and amodiaquine, for both a chloroquine-sensitive isolate (FCQ-27) and the chloroquine-resistant isolate (K1). At least one compound, 2,6-bis (piperidin-1''-ylmethyl)-4-(7'-trifluoromethylquinolin -4'-ylamino)phenol (TN112), showed significant superior activity to the three antimalarials chloroquine, mefloquine and amodiaquine against both isolates. (Statistically superior activity compared to these three antimalarials was found for TN112, except that against the K1 isolate its activity was just outside the range of significance relative to mefloquine.) Some of the 7-bromo-1,5-naphthyridine Mannich bases were appreciably less toxic in mice than amodiaquine.

Amines↗
PubMed1975

24xi-Methylcholestane-3beta, 5alpha, 6beta, 12beta, 25-pentol 25-monoacetate, a novel polyoxygenated marine sterol.

24xi--Methylcholestane-3beta, 5alpha, 6beta, 12beta, 25-pentol 25-monoacetate has been isolated from an Alyconarian and its structure was established in part through extensive high resolution mass spectral and nmr studies and partly through the nonidentity of one of its degradation products with 24xi-methylcholestane-3beta, 5alpha, 6beta, 12alpha-tetrol synthesized from deoxycholic acid.

Animals↗