Displaying publications 1 - 20 of 40 in total

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  1. Tan NH, Fung SY, Sim SM, Marinello E, Guerranti R, Aguiyi JC
    J Ethnopharmacol, 2009 Jun 22;123(2):356-8.
    PMID: 19429384 DOI: 10.1016/j.jep.2009.03.025
    The seed, leaf and root of Mucuna pruriens have been used in traditional medicine for treatments of various diseases. In Nigeria, the seed is used as oral prophylactics for snakebite.
  2. Fung SY, Tan NH, Liew SH, Sim SM, Aguiyi JC
    Trop Biomed, 2009 Apr;26(1):80-4.
    PMID: 19696731
    Seed of Mucuna pruriens (Velvet beans) has been prescribed by traditional medicine practitioners in Nigeria as a prophylactic oral antisnake remedy. In the present studies, we investigated the protective effects of M. pruriens seed extract (MPE) against histopathological changes induced by intravenous injection of Naja sputatrix (Malayan cobra) venom in rats pretreated with the seed extract. Examination by light microscope revealed that the venom induced histopathological changes in heart and blood vessels in liver, but no effect on brain, lung, kidney and spleen. The induced changes were prevented by pretreatment of the rats with MPE. Our results suggest that MPE pretreatment protects rat heart and liver blood vessels against cobra venom-induced damages.
  3. Fung SY, Tan NH, Sim SM, Marinello E, Guerranti R, Aguiyi JC
    Indian J Exp Biol, 2011 Apr;49(4):254-9.
    PMID: 21614888
    Mucuna pruriens has been used by native Nigerians as a prophylactic for snakebite. The protective effects of M. pruriens seed extract (MPE) were investigated against the pharmacological actions of N. sputatrix (Javan spitting cobra) venom in rats. The results showed that MPE-pretreatment protected against cardiorespiratory and, to a lesser extent, neuromuscular depressant effects of N. sputatrix venom. These may be explained at least in part by the neutralisation of the cobra venom toxins by anti-MPE antibodies elicited by the MPE pretreatment.
  4. Fung SY, Tan NH, Sim SM, Aguiyi JC
    PMID: 21785646 DOI: 10.1155/2012/486390
    Mucuna pruriens Linn. (velvet bean) has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE) have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra) venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value.
  5. Azila NM, Sim SM, Atiya AS
    Ann Acad Med Singap, 2001 Jul;30(4):375-8.
    PMID: 11503543
    INTRODUCTION: Encouraging teaching practices such as problem-based learning (PBL) amongst undergraduate students within a lecture-based, system-based integrated curriculum is a challenge. Students are apprehensive about developing an organised framework for acquiring knowledge while lecturers are required to reframe their views on the educational process and their role as educators.

    MATERIALS AND METHODS: Lecturers and students in the Phase (Year) II programme were asked to fill questionnaires following the second and fourth PBL cases. The two sets of survey responses were compared to see whether the students' and teachers' perceptions had changed over the 5-month period.

    RESULTS: Students' responses from both surveys (1 and 2) were similar in that a majority agreed that the PBL tutorials had encouraged the seeking of information (66% and 67%, respectively), had improved understanding (57% and 56%), integration (65% and 70%) and application (50% and 64%) of knowledge. However, the views given in the form of written comments, following their positive responses, were somewhat contradictory. A large number of students (38% and 40%) faced difficulties in getting involved in discussions during the PBL tutorial and a majority (73% and 82%) preferred the normal subject-based tutorials. The reasons given by approximately 20% of the students were that the subject-based tutorials were more efficient for obtaining information and/or that the information had been pre-selected by the lecturers. More than 80% of the lecturers (in both surveys) perceived that the students had identified the appropriate learning objectives and covered the subject matter. The percentage of lecturers who agreed that PBL tutorials encouraged rapport and teamwork amongst students had increased in the second survey, from 70% to 92% and 55% to 83% respectively.

    CONCLUSION: Implementing PBL is not simply a matter of developing new teaching materials and new effective ways of presenting them. It requires a paradigm shift, a change in the roles of students and teachers, and time.

  6. Sim SM, Hoggard PG, Sales SD, Phiboonbanakit D, Hart CA, Back DJ
    AIDS Res Hum Retroviruses, 1998 Dec 20;14(18):1661-7.
    PMID: 9870320
    Zidovudine (ZDV) is converted to its active triphosphate (ZDVTP) by intracellular kinases. The intermediate ZDV monophosphate (ZDVMP) is believed to play a major role in ZDV toxicity. Manipulation of ZDV phosphorylation is a possible therapeutic strategy for altering the risk-benefit ratio. Here we investigate whether combining RBV with ZDV is able to modulate efficacy and toxicity of ZDV. We have measured the intracellular activation of ZDV (0.3 microM) in the absence and presence of ribavirin (RBV; 2 and 20 microM) in Molt 4 and U937 cells. MTT cytotoxicity of ZDV (10-1000 microM) was also measured with and without RBV (2 microM) in Molt 4 and U937 cells. Measurement of endogenous deoxythymidine triphosphate (dTTP) allowed investigation of the dTTP/ZDVTP ratio. The antiviral efficacy of ZDV in combination with RBV (2 microM) was assessed by HIV p24 antigen measurements. In the presence of RBV (2 and 20 microM) a decrease in total ZDV phosphates was observed, owing mainly to an effect primarily on ZDVMP rather than the active ZDVTP. RBV also increased endogenous dTTP pools in both cell types, resulting in an increase in the dTTP/ZDVTP ratio. ZDV alone significantly reduced p24 antigen production, with an IC50 of 0.34 microM. Addition of RBV increased the IC50 approximately fivefold (1.52 microM). However, at higher concentrations of ZDV (10 and 100 microM) the antagonistic effect of RBV (2 microM) on ZDV was lost. The RBV-mediated decrease in ZDVMP may explain the reduction in ZDV toxicity when combined with RBV (2 microM). Cytotoxicity of ZDV was reduced in the presence of RBV (2 microM) at all concentrations in both cell lines, probably owing to saturation of ZDVTP formation. The interaction of ZDV and RBV is concentration dependent.
  7. Sim SM, Back DJ, Breckenridge AM
    Br J Clin Pharmacol, 1991 Jul;32(1):17-21.
    PMID: 1909542
    1. Zidovudine (3'-azido-3'-deoxythymidine; AZT) is the drug of proven efficacy available for the treatment of patients with AIDS or ARC. It is eliminated mainly by hepatic glucuronidation. Therefore, interference with this metabolic pathway may lead to enhancement of AZT effect or to increased toxicity of the drug. We have examined the effect of a number of drugs which themselves undergo glucuronidation on AZT conjugation by human liver microsomes in vitro. 2. AZT glucuronidation followed Michaelis-Menten kinetics. The apparent Km and Vmax values (mean +/- s.d., n = 5), were 2.60 +/- 0.52 mM and 68.0 +/- 23.4 nmol h-1 mg-1, respectively, as determined from Eadie-Hofstee plots. 3. Dideoxyinosine, sulphanilamide and paracetamol were essentially non-inhibitory at concentrations up to 10 mM (4 times the concentration of AZT in the incubation). The most marked inhibitory effects were seen with indomethacin, naproxen, chloramphenicol, probenecid and ethinyloestradiol, with enzyme activity decreased by 97.7, 94.9, 88.7, 83.4% and 79.0%, respectively, at a concentration of 10 mM. Other compounds producing some inhibition of AZT conjugation were oxazepam, salicylic acid and acetylsalicylic acid. 4. Further studies are necessary to characterise the inhibition observed but the method described enables a screen of potentially important drug interactions to be carried out.
  8. Lee CY, Sim SM, Cheng HM
    Nutr Res, 2008 Aug;28(8):555-63.
    PMID: 19083460 DOI: 10.1016/j.nutres.2008.05.001
    The use of a high quercetin dose to demonstrate its absorption and bioavailability does not reflect the real dietary situation because quercetin glycosides are usually present in small amounts in the human diet. This study aimed to demonstrate the absorption and bioavailability of quercetin in mulberry leaves that represents a more physiologic dietary situation. Mulberry leaf ethanol extract was prepared similar to tea infusion, which is the way the tea leaves are generally prepared for consumption. Accordingly, rats were fed by oral intubation the mulberry leaf ethanol extract (15 g%/rat per day) or pure rutin (135 microg/rat per day) for 2 weeks. The control group received a similar volume of the vehicle, 10% ethanol. There was a significant increase in total antioxidant activity (TAA) in the urine and feces of the antioxidants-fed rats. Phenylacetic acid, a microbial metabolite of quercetin, was detected in the urine of the test animals, and quercetin was present in the fecal samples. By using an in situ intestinal preparation, 3-hydroxyphenylacetic acid, another microbial metabolite of quercetin, was detected in the plasma when the duodenal segment was instilled with 2 mg of rutin. This microbial metabolite retained 50% of the TAA of quercetin. The results of this study indicate that in a more realistic dietary situation, an increase in TAA in the body after consumption of quercetin-containing foods is contributed mainly by the microbial metabolites.
  9. Chua SS, Lai PSM, Sim SM, Tan CH, Foong CC
    BMC Med Educ, 2019 Apr 05;19(1):101.
    PMID: 30953493 DOI: 10.1186/s12909-019-1525-y
    BACKGROUND: The success of interprofessional collaboration in healthcare services requires a paradigm shift in the training of future health profession practitioners. This study aimed to develop and validate an instrument to measure Student Acceptance of Interprofessional Learning (SAIL) in Malaysia, and to assess this attribute among medical and pharmacy students using a prescribing skills training workshop.

    METHODS: The study consisted of two phases. In Phase 1, a 10-item instrument (SAIL-10) was developed and tested on a cohort of medical and pharmacy students who attended the workshop. In Phase 2, different cohorts of medical and pharmacy students completed SAIL-10 before and after participating in the workshop.

    RESULTS: Factor analysis showed that SAIL-10 has two domains: "facilitators of interprofessional learning" and "acceptance to learning in groups". The overall SAIL-10 and the two domains have adequate internal consistency and stable reliability. The total score and scores for the two domains were significantly higher after students attended the prescribing skills workshop.

    CONCLUSIONS: This study produced a valid and reliable instrument, SAIL-10 which was used to demonstrate that the prescribing skills workshop, where medical and pharmacy students were placed in an authentic context, was a promising activity to promote interprofessional learning among future healthcare professionals.

  10. Yap MK, Tan NH, Sim SM, Fung SY
    Toxicon, 2013 Jun;68:18-23.
    PMID: 23537711 DOI: 10.1016/j.toxicon.2013.02.017
    Existing protocols for antivenom treatment of snake envenomations are generally not well optimized due partly to inadequate knowledge of the toxicokinetics of venoms. The toxicokinetics of Naja sputatrix (Javan spitting cobra) venom was investigated following intravenous and intramuscular injections of the venom into rabbits using double-sandwich ELISA. The toxicokinetics of the venom injected intravenously fitted a two-compartment model. When the venom was injected intramuscularly, the serum concentration-time profile exhibited a more complex absorption and/or distribution pattern. Nevertheless, the terminal half-life, volume of distribution by area and systemic clearance of the venom injected intramuscularly were not significantly different (p > 0.05) from that of the venom injected intravenously. The systemic bioavailability of the venom antigens injected by intramuscular route was 41.7%. Our toxicokinetic finding is consistent with other reports, and may indicate that some cobra venom toxins have high affinity for the tissues at the site of injection. Our results suggest that the intramuscular route of administration doesn't significantly alter the toxicokinetics of N. sputatrix venom although it significantly reduces the systemic bioavailability of the venom.
  11. Sim SM, Achike FI, Geh SL
    Med J Malaysia, 2005 Aug;60 Suppl D:41-7.
    PMID: 16315623
    In Malaysia many new medical schools (both public and private) have been set up in the last 12 years. As a result of global changes and local adjustments made in medical training, cross-breeds of different medical curricula have produced a wide spectrum of teaching-learning methods in these medical schools. In this paper, we have selected three medical schools--two public (Universiti Malaya and Universiti Putra Malaysia) and one private (International Medical University) to illustrate different approaches in the teaching-learning of pharmacology that exist in Malaysia. How do these different teaching-learning approaches affect the students' interest and ability to "master" pharmacology and in turn to develop a good prescribing practice?
  12. Tan CH, Tan NH, Sim SM, Fung SY, Gnanathasan CA
    Acta Trop, 2012 Jun;122(3):267-75.
    PMID: 22322247 DOI: 10.1016/j.actatropica.2012.01.016
    Envenomation by hump-nosed pit viper (Hypnale hypnale, Hh) in Sri Lanka has caused significant morbidity and mortality, attributed to 35% of total venomous snakebites. In Southwestern India (Kerala), H. hypnale was increasingly identified as a dangerous and common source of envenomation, second to the Russell's viper but ahead of the cobra bites. Unfortunately, there is still no specific antivenom to date. This study aims to investigate the immunological properties of the venom and to assess the feasibility of specific Hh antivenom production as well as the development of a diagnostic assay. Hh venom elicited satisfactory titers of anti-Hh IgG in rabbits after 3rd immunization. The anti-Hh IgG, isolated with caprylic acid precipitation method, was effective in neutralizing the venom lethality (potency=48 LD(50) per ml IgG) as well as its procoagulant, hemorrhagic and necrotic effects, indicating the possibility to produce the specific antivenom using the common immunization regime. Cross-reactivity studies using indirect ELISA showed that anti-Hh IgG cross-reacted extensively with several Asiatic crotalid venoms, particularly that of Calloselasma rhodostoma (73.6%), presumably due to the presence of venom antigens common to both snakes. Levels of immunological cross-reactivity were vastly reduced with double-sandwich ELISA. Further work demonstrated that the assay was able to distinguish and quantify venoms of H. hypnale, Daboia russelii and Echis carinatus sinhaleyus (three common local viperid) used to spike human sera at various concentrations. The assay hence may be a useful investigating tool for diagnosing biting species and studying the time course profile of venom concentrations in blood.
  13. Tan CH, Tan NH, Sim SM, Fung SY, Gnanathasan CA
    Toxicon, 2015 Jan;93:164-70.
    PMID: 25451538 DOI: 10.1016/j.toxicon.2014.11.231
    The hump-nosed pit viper, Hypanle hypnale, contributes to snakebite mortality and morbidity in Sri Lanka. Studies showed that the venom is hemotoxic and nephrotoxic, with some biochemical and antigenic properties similar to the venom of Calloselasma rhodostoma (Malayan pit viper). To further characterize the complexity composition of the venom, we investigated the proteome of a pooled venom sample from >10 Sri Lankan H. hypnale with reverse-phase high performance liquid chromatography (rp-HPLC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and peptide sequencing (tandem mass-spectrometry and/or N-terminal sequencing). The findings ascertained that two phospholipase A2 subtypes (E6-PLA2, W6-PLA2) dominate the toxin composition by 40.1%, followed by snake venom metalloproteases (36.9%), l-amino acid oxidase (11.9%), C-type lectins (5.5%), serine proteases (3.3%) and others (2.3%). The presence of the major toxins correlates with the venom's major pathogenic effects, indicating these to be the principal target toxins for antivenom neutralization. This study supports the previous finding of PLA2 dominance in the venom but diverges from the view that H. hypnale venom has low expression of large enzymatic toxins. The knowledge of the composition and abundance of toxins is essential to elucidate the pathophysiology of H. hypnale envenomation and to optimize antivenom formulation in the future.
  14. Tan CH, Tan NH, Sim SM, Fung SY, Jayalakshmi P, Gnanathasan CA
    Toxicon, 2012 Dec 1;60(7):1259-62.
    PMID: 22975088 DOI: 10.1016/j.toxicon.2012.08.012
    Mice experimentally envenomed with Hypnale hypnale venom (1× and 1.5×LD₅₀) developed acute kidney injury (AKI) principally characterized by raised blood urea and creatinine. Prolonged blood clotting time and hemorrhage in lungs implied bleeding tendency. Pallor noted in most renal cortices was suggestive of renal ischemia secondary to consumptive coagulopathy. Intravenous infusion of Hemato polyvalent antivenom following experimental envenoming effectively prevented death and AKI in all mice, supporting its potential therapeutic use in envenoming cases.
  15. Devi RC, Sim SM, Ismail R
    J Smooth Muscle Res, 2011;47(5):143-56.
    PMID: 22104376
    Cymbopogon citratus, commonly known as lemongrass, has been shown to have antioxidant, antimicrobial and chemo-protective properties. Citral, a monoterpenoid, is the major constituent of C. citratus that gives off a lemony scent and is postulated to be responsible for most of its actions. In addition, C. citratus has been traditionally used to treat gastrointestinal discomforts, however, the scientific evidence for this is still lacking. Thus, the aim of the present study was to investigate the effect of the extracts of various parts of C. citratus (leaves, stems and roots) and citral on the visceral smooth muscle activity of rabbit ileum. The effect of the test substances were tested on the spontaneous contraction, acetylcholine (ACh)- and KCl-induced contractions. Citral at doses between 0.061 mM to 15.6 mM and the extract of leaves at doses between 0.001 mg/mL to 1 mg/mL significantly reduced the spontaneous, ACh- and KCl-induced ileal contractions. When the ileum was incubated in K(+)-rich-Ca(2+)-free Tyrode's solution, it showed only minute contractions. However, the strength of contraction was increased with the addition of increasing concentrations of CaCl(2). The presence of citral almost abolished the effect of adding CaCl(2), while the leaf extract shifted the calcium concentration-response curve to the right, suggesting a calcium antagonistic effect. These results were similar to that elicited by verapamil, a known calcium channel blocker. In addition, the spasmolytic effect of citral was observed to be reduced by the nitric oxide synthase inhibitor, L-NAME. In conclusion, citral and the leaf extract of C. citratus exhibited spasmolytic activity and it appeared that they may act as calcium antagonists. Furthermore, the relaxant effect of citral, but not that of the leaf extract may be mediated by nitric oxide suggesting the presence of other chemical components in the leaf extract other than citral.
  16. Devi RC, Sim SM, Ismail R
    PMID: 22675383 DOI: 10.1155/2012/539475
    Cymbopogon citratus has been shown to have antioxidant, antimicrobial, antispasmodic and chemo-protective properties. Citral, is the major constituent of C. citratus. This study investigated the effects of methanolic extracts of leaves (LE), stems (SE), and roots (RE) of C. citratus and citral on vascular smooth muscle and explored their possible mechanisms of action. The experiment was conducted using isolated tissue preparations, where citral, LE, SE, and RE were added separately into a tissue bath that contained aortic rings, which were pre-contracted with phenylephrine (PE). Citral, LE, and RE exhibited a dose-dependent relaxant effect on the PE-induced contractions. Citral appeared to partially act via NO as its vasorelaxant effect was attenuated by L-NAME. However, the effect of LE may involve prostacyclin as indomethacin reversed the relaxant effect of LE on the PE-induced contraction. Furthermore, citral, LE, and RE abolished the restoration of PE-induced contraction caused by the addition of increasing doses of calcium in both endothelium intact and denuded rings. These findings suggest that the relaxation effect of citral, LE, and RE is endothelium-independent and may be mainly by affecting the intracellular concentration of calcium. Citral may partially act through the NO pathway while a vasodilator prostaglandin may mediate the effect of LE.
  17. Lee SS, Tan NH, Fung SY, Sim SM, Tan CS, Ng ST
    PMID: 25256382 DOI: 10.1186/1472-6882-14-359
    The sclerotium of Lignosus rhinocerotis (Cooke) Ryvarden (Tiger Milk mushroom) is used as a traditional medicine to relieve cough, asthma and chronic hepatitis. The traditional uses of the sclerotium are presumably related to its anti-inflammatory effect. The present study was carried out to evaluate the anti-inflammatory activity of the sclerotial powder of L. rhinocerotis (Cooke) Ryvarden (Tiger Milk mushroom) cultivar TM02.
  18. Sim SM, Rasiah RI
    Ann Acad Med Singap, 2006 Feb;35(2):67-71.
    PMID: 16565756
    INTRODUCTION: This paper reports the relationship between the difficulty level and the discrimination power of true/false-type multiple-choice questions (MCQs) in a multidisciplinary paper for the para-clinical year of an undergraduate medical programme.

    MATERIALS AND METHODS: MCQ items in papers taken from Year II Parts A, B and C examinations for Sessions 2001/02, and Part B examinations for 2002/03 and 2003/04, were analysed to obtain their difficulty indices and discrimination indices. Each paper consisted of 250 true/false items (50 questions of 5 items each) on topics drawn from different disciplines. The questions were first constructed and vetted by the individual departments before being submitted to a central committee, where the final selection of the MCQs was made, based purely on the academic judgement of the committee.

    RESULTS: There was a wide distribution of item difficulty indices in all the MCQ papers analysed. Furthermore, the relationship between the difficulty index (P) and discrimination index (D) of the MCQ items in a paper was not linear, but more dome-shaped. Maximal discrimination (D = 51% to 71%) occurred with moderately easy/difficult items (P = 40% to 74%). On average, about 38% of the MCQ items in each paper were "very easy" (P > or =75%), while about 9% were "very difficult" (P <25%). About two-thirds of these very easy/difficult items had "very poor" or even negative discrimination (D < or =20%).

    CONCLUSIONS: MCQ items that demonstrate good discriminating potential tend to be moderately difficult items, and the moderately-to-very difficult items are more likely to show negative discrimination. There is a need to evaluate the effectiveness of our MCQ items.

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