PubMed Health⌕ Search

Biomedical subjects

Eugene Tan

Publications and source records attributed to Eugene Tan.

7 recordsLinked to original sources
PubMed2005

Vascular binding, blood flow, transporter, and enzyme interactions on the processing of digoxin in rat liver.

The roles of vascular binding, flow, transporters, and enzymes as determinants of the clearance of digoxin were examined in the rat liver. Digoxin is metabolized by Cyp3a and utilizes the organic anion transporting polypeptide 2 (Oatp2) and P-glycoprotein (Pgp) for influx and excretion, respectively. Uptake of digoxin was found to be similar among rat periportal (PP) and perivenous (PV) hepatocytes isolated by the digitonin-collagenase method. The Km values for uptake were 180 +/- 112 and 390 +/- 406 nM, Vmax values were 13 +/- 8 and 18 +/- 4.9 pmol/min/mg protein, and nonsaturable components were 9.2 +/- 1.3 and 10.7 +/- 2.5 microl/min/mg for PP and PV, respectively. The evenness of distribution of Oatp2 and Pgp was confirmed by Western blotting and confocal immunofluorescent microscopy. When digoxin was recirculated to the rat liver preparation in Krebs-Henseleit bicarbonate (KHB) for 3 h in absence or presence of 1% bovine serum albumin (BSA) and 20% red blood cell (rbc) at flow rates of 40 and 10 ml/min, respectively, biexponential decays were observed. Fitted results based on compartmental analyses revealed a higher clearance (0.244 +/- 0.082 ml/min/g) for KHB-perfused livers over the rbc-albumin-perfused livers (0.114 +/- 0.057 ml/min/g) (P < 0.05). We further found that binding of digoxin to 1% BSA was modest (unbound fraction = 0.64), whereas binding to rbc was associated with slow on (0.468 +/- 0.021 min(-1)) and off (1.81 +/- 0.12 min(-1)) rate constants. We then used a zonal, physiologically based pharmacokinetic model to show that the difference in digoxin clearance was attributed to binding to BSA and rbc and not to the difference in flow rate and that clearance was unaffected by transporter or enzyme heterogeneity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Simultaneous multiple vector distraction for craniosynostosis syndromes.

Syndromic craniosynostoses are commonly treated conditions in craniofacial units. The features of the common syndromes (Apert, Pfeiffer and Crouzon) all include craniosynostosis, mid-face hypoplasia and ocular proptosis. The craniofacial management of a child with these syndromes through to adulthood may require a number of surgical interventions to allow brain development, to provide an adequate airway, to prevent corneal ulceration and to provide a functional dental occlusion. The management of these different priorities into timed interventions in our unit is determined by established protocols. We report two cases that underwent simultaneous mid-face (Le Fort III) and fronto-orbital osteotomies followed by distraction but using different vectors to advance the upper and mid-face regions (to achieve all treatment goals) in a 12-year-old boy and a 16-year-old girl.

Acrocephalosyndactylia↗
PubMed2004

Changes in the use of Hormone Replacement Therapy in New Zealand following the publication of the Women's Health Initiative trial.

BACKGROUND: Results of the Women's Health Initiative (WHI) trial on Hormone Replacement Therapy (HRT) have recently been published. We carried out a national survey to assess the impact of the July 2002 findings on HRT use. We also studied where women obtained information, as well as their opinions and beliefs. METHODS: 500 women aged 45 to 64 years were randomly selected from the electoral rolls, and were sent a questionnaire regarding use and knowledge of HRT. There was phone follow-up for those who did not reply. Variables were tested for associations using the Chi-squared test and adjusted for confounding. RESULTS: We received 298 questionnaires back, and a further 20 responses were received by phone (response rate 66%). We found that 15% of women were taking HRT during June 2002 compared to 11% taking HRT in December 2002, a drop of 36%. Even in July 2002, only 2% of users reported taking it to prevent coronary heart disease. Findings from the WHI trial were the main reason for stopping HRT. Women expressed an interest in more 'natural' therapies over HRT. Most women had heard information on HRT, however knowledge was lacking in some areas. CONCLUSIONS: The publicity following publication of the WHI trial has led to a decline in HRT use in New Zealand consistent with national sales data. Nevertheless, most women were not using HRT for heart disease prevention even before the WHI trial was published, suggesting that the NZ Guidelines Group 2001 recommendation against such use had been widely acted on. Women have expressed an interest in alternative therapies and more research is required in these areas. Methods of stopping HRT are understudied.

Data Collection↗
PubMed2004

Effect of quinidine on the 10-hydroxylation of R-warfarin: species differences and clearance projection.

Stimulation by quinidine of warfarin metabolism in vitro was first demonstrated with liver microsomal preparations. We report herein that this drug interaction is reproducible in an animal model but that it exhibits profound species differences. Thus, using rabbit liver microsomes and a kinetic model incorporating two binding sites, the hepatic intrinsic clearance of R-warfarin via the 10-hydroxylation pathway (CL(int)(W)) was projected to be 6 +/- 1 and 128 +/- 51 microl/min/g liver, respectively, in the absence and presence of 21 microM unbound quinidine. These estimates were consistent with the results from studies in which rabbit livers (n = 5) were perfused in situ with R-warfarin or R-warfarin plus quinidine. The CL(int)(W) increased from 7 +/- 3 to 156 +/- 106 microl/min/g liver after increasing the hepatic exposure of unbound quinidine from 0 to 21 microM. In contrast, when liver microsomes or intact livers from rats were examined, R-warfarin metabolism was inhibited by quinidine, the CL(int)(W) decreasing to 26% of the control value after exposure of perfused rat livers (n = 5) to 22 microM unbound quinidine. The third example involved monkey liver microsomes, in which the rate of 10-hydroxylation of R-warfarin was little affected in the presence of quinidine (<2-fold increase). In all three species, the 10-hydroxylation of R-warfarin was catalyzed primarily by members of CYP3A, based on immuno- and chemical inhibition analyses. These findings not only highlight the variability of drug interactions among different species but also suggest that changes in hepatic clearance resulting from stimulation of cytochrome P450 activity may be projected based on estimates generated from corresponding liver microsomal preparations.

Animals↗
PubMed2003

Test your knowledge. Patient with a skin rash.

A fit and healthy 22 year old of Asian ancestry, living in New Zealand with no previous history of asthma or dermatitis, visited the Gold Coast, Queensland, for a vacation. Having been cautioned about the intensity of the Australian sun, he arrived armed with a hat and new SPF130 sunscreen that he had obtained from Japan. On the third day of his vacation he noticed the appearance of many erythematous papules and some vesicles on the dorsum of the forearm, arm and the 'v' of the neck. His face was spared. On the fourth day, the papules coalesced to form swollen, warm, very pruritic, erythematous plaques (Figure 1). The patient commenced taking loratadine 10 mg per day, but did not improve after seven days of treatment.

Adult↗
PubMed2002

Comparison of new and 3-month-old toothbrushes in plaque removal.

OBJECTIVES: It is often recommended that manual toothbrushes should be replaced every 3 months. The aim of this study was to compare the effectiveness of new and 3-month-old toothbrushes in the removal of dental plaque. MATERIALS AND METHODS: A single examiner blind, randomized study was performed in which 40 adult patients attended the clinic on two occasions following 48-h periods of no oral hygiene. Following plaque scoring, patients brushed with a new toothbrush at one visit and with a brush that they had used previously for 3 months at the other visit. Brushing time was 60 s. Plaque was then re-scored and percentage reductions in plaque scores calculated. The amount of wear of the 3-month-old brushes was determined by measurement of brushing surface areas. RESULTS: Plaque scores after each 48-h period of no oral hygiene were not significantly different. The percentage reductions in plaque scores achieved with the new brushes were not significantly different from those achieved with the 3-month-old brushes. Both the new and the 3-month-old toothbrushes reduced plaque scores by approximately 34%. Compared with new brushes in the same subjects, no significant differences were found for plaque score reductions for 3-month-old brushes with minor, moderate or marked wear. CONCLUSION: The 3-month-old toothbrushes were as effective as new brushes in plaque removal.

Adult↗