Displaying publications 1 - 20 of 31 in total

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  1. Haerian BS, Lim KS, Tan HJ, Mohamed EH, Tan CT, Raymond AA, et al.
    Epileptic Disord, 2011 Mar;13(1):65-75.
    PMID: 21388909 DOI: 10.1684/epd.2011.0419
    Over-expression of P-glycoprotein, encoded by the ABCB1 gene, is proposed to be involved in resistance to antiepileptic drugs in about 30% of patients with epilepsy. Here, we investigated the possible association between ABCB1 polymorphisms and sodium valproate (VPA) treatment in Malaysian epilepsy patients. Genotypes were assessed in 249 drug-resistant and 256 drug-responsive Malaysian patients for C1236T, G2677T/A, and C 5T polymorphisms in the ABCB1 gene. No genotypes, alleles, or haplotypes were associated with the response to VPA in either the overall group or Chinese, Indian, and Malay subgroups. Our data suggest that C1236T, G2677T/A, and C3435T polymorphisms in the ABCB1 gene do not contribute to the response to VPA in patients with epilepsy.
  2. Chia PL, Earnest A, Lee R, Lim J, Wong CP, Chia YW, et al.
    Ann Acad Med Singap, 2013 Sep;42(9):432-6.
    PMID: 24162317
    INTRODUCTION: In Singapore, the age-standardised event rates of myocardial infarction (MI) are 2- and 3-fold higher for Malays and Indians respectively compared to the Chinese. The objectives of this study were to determine the prevalence and quantity of coronary artery calcification (CAC) and non-calcified plaques across these 3 ethnic groups.

    MATERIALS AND METHODS: This was a retrospective descriptive study. We identified 1041 patients (810 Chinese, 139 Malays, 92 Indians) without previous history of cardiovascular disease who underwent cardiac computed tomography for atypical chest pain evaluation. A cardiologist, who was blinded to the patients' clinical demographics, reviewed all scans. We retrospectively analysed all their case records.

    RESULTS: Overall, Malays were most likely to be active smokers (P = 0.02), Indians had the highest prevalence of diabetes mellitus (P = 0.01) and Chinese had the highest mean age (P <0.0001). The overall prevalence of patients with non-calcified plaques as the only manifestation of sub-clinical coronary artery disease was 2.1%. There was no significant difference in the prevalence of CAC, mean CAC score or prevalence of non-calcified plaques among the 3 ethnic groups. Active smoking, age and hypertension were independent predictors of CAC. Non-calcified plaques were positively associated with male gender, age, dyslipidaemia and diabetes mellitus.

    CONCLUSION: The higher MI rates in Malays and Indians in Singapore cannot be explained by any difference in CAC or non-calcified plaque. More research with prospective follow-up of larger patient populations is necessary to establish if ethnic-specific calibration of CAC measures is needed to adjust for differences among ethnic groups.

  3. Haerian BS, Lim KS, Mohamed EH, Tan HJ, Tan CT, Raymond AA, et al.
    Seizure, 2011 Sep;20(7):546-53.
    PMID: 21530324 DOI: 10.1016/j.seizure.2011.04.003
    Approximately one third of newly treated epilepsy patients do not respond to antiepileptic drugs (AEDs). Overexpression of P-glycoprotein (P-gp) efflux transporter has been proposed to have a critical role in causing resistance to AEDs. P-gp is a product of the ATP-binding cassette subfamily B member 1 (ABCB1) gene. The purpose of this study was to investigate a possible link between ABCB1 rs3789243 C>T, C1236T, G2677T/A, rs6949448 C>T, and C3435T haplotypes with response to carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in Malaysian epilepsy patients. No ABCB1 haplotype association was found with response to either CBZ or VPA monotherapy in the Chinese, Indian, and Malay patients. C3435 allele carriers of the Indian males with cryptogenic epilepsy were more prone to resistance to either CBZ or VPA than carriers of T allele. Moreover, rs3789243T allele carriers of Malay females with symptomatic epilepsy were more resistant to either CBZ or VPA than C allele carriers. Our findings suggest that the ABCB1 rs3789243 C>T, C1236T, G2677T/A, rs6949448 C>T, and C3435T haplotypes do not contribute to response to AED treatment in epilepsy.
  4. Haerian BS, Lim KS, Tan HJ, Wong CP, Wong SW, Tan CT, et al.
    Synapse, 2011 Oct;65(10):1073-9.
    PMID: 21465568 DOI: 10.1002/syn.20939
    The SYN2 rs3773364 A>G polymorphism has been proposed to be involved in susceptibility to epilepsy, but research results have been inconclusive. The aim of this study was to investigate the association between the SYN2 rs3773364 A>G polymorphism and susceptibility against epilepsy in a case-control study and a meta-analysis.
  5. Haerian BS, Lim KS, Mohamed EH, Tan HJ, Tan CT, Raymond AA, et al.
    Seizure, 2011 Jun;20(5):387-94.
    PMID: 21316268 DOI: 10.1016/j.seizure.2011.01.008
    It is proposed that overexpression of P-glycoprotein (P-gp), encoded by the ABC subfamily B member 1 (ABCB1) gene, is involved in resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation and haplotype patterns are population specific which may cause different phenotypes such as response to AEDs. Although several studies examined the link between the common polymorphisms in the ABCB1 gene with resistance to AEDs, the results have been conflicting. This controversy may be caused by the effect of some confounders such as ethnicity and polytherapy. Moreover, expression of the ABCB1 gene is under the control of pregnane X receptor (PXR). Evidence showed that PXR gene contribute to the response to treatment. The aim of this study was to assess the association of ABCB1 and PXR genetic polymorphisms with response to the carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in epilepsy. Genotypes were assessed in 685 Chinese, Indian, and Malay epilepsy patients for ABCB1 (C1236T, G2677T, C3435T) and PXR (G7635A) polymorphisms. No association between these polymorphisms and their haplotypes, and interaction between them, with response to treatment was observed in the overall group or in the Chinese, Indian, and Malay subgroups. Our data showed that these polymorphisms may not contribute to the response to CBZ or VPA monotherapy treatment in epilepsy.
  6. Wong CP, Seki A, Horiguchi K, Shoji T, Arai T, Nugroho AE, et al.
    J Nat Prod, 2015 Jul 24;78(7):1656-62.
    PMID: 26176165 DOI: 10.1021/acs.jnatprod.5b00258
    We have previously reported that bisleuconothine A (Bis-A), a novel bisindole alkaloid isolated from Leuconotis griffithii, showed cytostatic activity in several cell lines. In this report, the mechanism of Bis-A-induced cytostatic activity was investigated in detail using A549 cells. Bis-A did not cause apoptosis, as indicated by analysis of annexin V and propidium iodide staining. Expression of all tested apoptosis-related proteins was also unaffected by Bis-A treatment. Bis-A was found to increase LC3 lipidation in MCF7 cells as well as A549 cells, suggesting that Bis-A cytostatic activity may be due to induction of autophagy. Subsequent investigation via Western blotting and immunofluorescence staining indicated that Bis-A induced formation but prevented degradation of autophagosomes. Mechanistic studies showed that Bis-A down-regulated phosphorylation of protein kinase B (AKT) and its downstream kinase, PRAS40, which is an mTOR repressor. Moreover, phosphorylation of p70S6K, an mTOR-dependent kinase, was also down-regulated. Down-regulation of these kinases suggests that the increase in LC3 lipidation may be due to mTOR deactivation. Thus, the cytostatic activity shown by Bis-A may be attributed to its induction of autophagosome formation. The Bis-A-induced autophagosome formation was suggested to be caused by its interference with the AKT-mTOR signaling pathway.
  7. Wo SW, Lai PS, Ong LC, Low WY, Lim KS, Tay CG, et al.
    Epilepsy Behav, 2015 Apr;45:118-23.
    PMID: 25819800 DOI: 10.1016/j.yebeh.2015.02.037
    We aimed to cross-culturally adapt the parent-proxy Health-Related Quality of Life Measure for Children with Epilepsy (CHEQOL-25) into Malay and to determine its validity and reliability among parents of children with epilepsy in Malaysia.
  8. Choo BKM, Kundap UP, Johan Arief MFB, Kumari Y, Yap JL, Wong CP, et al.
    PMID: 30844417 DOI: 10.1016/j.pnpbp.2019.02.014
    Epilepsy is marked by seizures that are a manifestation of excessive brain activity and is symptomatically treatable by anti-epileptic drugs (AEDs). Unfortunately, the older AEDs have many side effects, with cognitive impairment being a major side effect that affects the daily lives of people with epilepsy. Thus, this study aimed to determine if newer AEDs (Zonisamide, Levetiracetam, Perampanel, Lamotrigine and Valproic Acid) also cause cognitive impairment, using a zebrafish model. Acute seizures were induced in zebrafish using pentylenetetrazol (PTZ) and cognitive function was assessed using the T-maze test of learning and memory. Neurotransmitter and gene expression levels related to epilepsy as well as learning and memory were also studied to provide a better understanding of the underlying processes. Ultimately, impaired cognitive function was seen in AED treated zebrafish, regardless of whether seizures were induced. A highly significant decrease in γ-Aminobutyric Acid (GABA) and glutamate levels was also discovered, although acetylcholine levels were more variable. The gene expression levels of Brain-Derived Neurotrophic Factor (BDNF), Neuropeptide Y (NPY) and Cyclic Adenosine Monophosphate (CAMP) Responsive Element Binding Protein 1 (CREB-1) were not found to be significantly different in AED treated zebrafish. Based on the experimental results, a decrease in brain glutamate levels due to AED treatment appears to be at least one of the major factors behind the observed cognitive impairment in the treated zebrafish.
  9. Iijima C, Wong CP, Nugroho AE, Sotozono Y, Someya S, Hirasawa Y, et al.
    J Nat Med, 2016 Oct;70(4):702-7.
    PMID: 27357963 DOI: 10.1007/s11418-016-1016-y
    The ceramicines, a series of limonoids from Chisocheton ceramicus (Meliaceae), were evaluated for anti-melanin deposition activity on α-melanocyte stimulating hormone (α-MSH) and 3-isobutyl-1-methylxanthine (IBMX)-treated B16-F10 melanoma cell, and several ceramicines were found to be active. The structure-activity relationship of ceramicines as anti-melanin deposition inhibitors was deduced. Furthermore, the mechanism of anti-melanin deposition activity of ceramicine B, a major constituent of C. ceramicus that showed potent anti-melanin deposition activity, was investigated. Tyrosinase enzymatic activity and tyrosinase mRNA expression were not affected by ceramicine B. The anti-melanin deposition activity of ceramicine B was shown to be related to the downregulation of tyrosinase protein expression. These results suggest that ceramicines have potential to be used as depigmentation agents.
  10. Nugroho AE, Nakajima S, Wong CP, Hirasawa Y, Kaneda T, Shirota O, et al.
    J Nat Med, 2022 Jan;76(1):94-101.
    PMID: 34351584 DOI: 10.1007/s11418-021-01556-4
    Eight new limonoids, walsogynes H-O (1-8) were isolated from the barks of Walsura chrysogyne, and their structures were determined on the basis of the 1D and 2D NMR data. Walsogynes H-M (1-6) and O (8) were concluded to be 11,12-seco limonoids with a dodecahydro-1H-naphtho[1,8-bc:3,4-c']difuran skeleton, and walsogyne N (7) to be 11,12-seco limonoid sharing a unique dodecahydronaphtho[1,8-bc:5,4-b'c']difuran skeleton. Walsogynes H-O (1-8) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 2.5, 2.6, 1.6, 2.5, 1.5, 2.6, 2.1, and 1.1 µM, respectively.
  11. Nugroho AE, Komuro T, Kawaguchi T, Shindo Y, Wong CP, Hirasawa Y, et al.
    J Nat Med, 2024 Jan;78(1):68-77.
    PMID: 37690111 DOI: 10.1007/s11418-023-01746-2
    Ceramicines are a series of limonoids which were isolated from the barks of Malaysian Chisocheton ceramicus (Meliaceae), and were known to show various biological activity. Six new limonoids, ceramicines U-Z (1-6), with a cyclopentanone[α]phenanthrene ring system with a β-furyl ring at C-17 were isolated from the barks of C. ceramicus. Their structures were determined on the basis of the 1D and 2D NMR analyses, and their absolute configurations were investigated by CD spectroscopy. Ceramicine W (3) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 1.2 µM. In addition, the structure-antimalarial activity relationship (SAR) of the ceramicines was investigated to identify substituent patterns that may enhance activity. It appears that ring B and the functional groups in the vicinity of rings B and C are critical for the antimalarial activity of the ceramicines. In particular, bulky ester substituents with equatorial orientation at C-7 and C-12 greatly increase the antimalarial activity.
  12. Tay EL, Lee SWH, Jamaluddin SF, Tam CL, Wong CP
    BMC Pediatr, 2016 04 27;16:56.
    PMID: 27122016 DOI: 10.1186/s12887-016-0590-1
    BACKGROUND: There are limited studies describing the epidemiology of childhood brain injury, especially in developing countries. This study analyses data from the Malaysian National Trauma Database (NTrD) registry to estimate the incidence of childhood brain injury among various demographic groups within the state of Selangor and Federal Territory of Kuala Lumpur.

    METHODS: This study analysed all traumatic brain injury cases for children ages 0-19 included in the 2010 NTrD report.

    RESULTS: A total of 5,836 paediatric patients were admitted to emergency departments (ED) of reporting hospitals for trauma. Of these, 742 patients (12.7 %) suffered from brain injuries. Among those with brain injuries, the mortality rate was 11.9 and 71.2 % were aged between 15 and 19. Traffic accidents were the most common mode of injury (95.4 %). Out of the total for traffic accidents, 80.2 % of brain injuries were incurred in motorcycle accidents. Severity of injury was higher among males and patients who were transferred or referred to the reporting centres from other clinics. Glasgow Coma Scale (GCS) total score and type of admission were found to be statistically significant, χ (2) (5, N = 178) = 66.53, p 

  13. Chie QT, Tam CL, Bonn G, Wong CP, Dang HM, Khairuddin R
    Front Psychiatry, 2015;6:65.
    PMID: 25999867 DOI: 10.3389/fpsyt.2015.00065
    In recent years, there have been increasing accounts of illegal substance abuse among university students and professional groups in Malaysia. This study looks at university students' perceptions about this phenomenon. Students from Malaysian universities were asked for their impressions about drug availability and abuse, as well as factors contributing to drug abuse and relapse. The questionnaire also inquired into their knowledge and views regarding government versus private rehabilitation centers, as well as their exposure to, and views about, school-based drug-prevention education. Participants were 460 university students from five Malaysian states: Penang, Selangor, Kuala Lumpur, Sabah, and Sarawak. Results showed gender differences in perceptions of relapse prevention strategies, as well as factors leading to drug abuse and relapse. Students also believed that drug education would be more effective if initiated between the ages of 11 and 12 years, which is slightly older than the common age of first exposure, and provided suggestions for improving existing programs. Implications of student perceptions for the improvement of current interventions and educational programs are discussed.
  14. Lee JY, Lee SW, Nasir NH, How S, Tan CS, Wong CP
    Diabet Med, 2015 Dec;32(12):1658-61.
    PMID: 26103794 DOI: 10.1111/dme.12836
    AIM: This pilot study evaluated the short-term benefits of a telemonitoring-supplemented focused diabetic education compared with education alone in participants with Type 2 diabetes who were fasting during Ramadan.
    METHODS: In this pilot mixed-method study, we identified 37 participants and randomly allocated them to either a telemonitoring group (n = 18) or a group receiving Ramadan-focused pre-education only (usual care; n = 19). The telemonitoring group received goal-setting and personalized feedback.
    RESULTS: The telemonitoring group was less likely to experience hypoglycaemia than the usual care group (odds ratio: 0.1273; 95% confidence interval: 0.0267-0.6059). No significant differences were noted in glycaemic control at the end of study. Participants viewed telemedicine as a more convenient alternative although technological barriers remain a concern.
    CONCLUSIONS: The results of this study reinforce the need for monitoring as well as educational initiatives for Muslims with diabetes who fast during Ramadan. Telemonitoring offers an attractive option requiring further research. (Clinical Trial Registry No. NCT02189135).
  15. Nugroho AE, Inoue D, Wong CP, Hirasawa Y, Kaneda T, Shirota O, et al.
    J Nat Med, 2018 Mar;72(2):588-592.
    PMID: 29453649 DOI: 10.1007/s11418-018-1188-8
    Bioactivity guided separation of Reinwardtiodendron cinereum barks methanol extract led to the isolation of two new onocerane triterpenoids, reinereins A and B (1 and 2), together with three known onocerane triterpenoids. Their structures were elucidated on the basis of NMR spectroscopic data. In vitro cytotoxic activities of the isolated compounds against several type of cancer cells were evaluated.
  16. Nugroho AE, Hashimoto A, Wong CP, Yokoe H, Tsubuki M, Kaneda T, et al.
    J Nat Med, 2019 Jun;73(3):682.
    PMID: 30945063 DOI: 10.1007/s11418-019-01301-y
    The article Ceramicines M-P from Chisocheton ceramicus: isolation and structure-activity relationship study.
  17. Lee JY, Wong CP, Tan CSS, Nasir NH, Lee SWH
    BMJ Open Diabetes Res Care, 2017;5(1):e000365.
    PMID: 28761651 DOI: 10.1136/bmjdrc-2016-000365
    OBJECTIVE: We evaluated the beliefs, experience and diabetes management strategies of type 2 diabetes mellitus (T2DM) Muslim patients that chose to fast during Ramadan.
    RESEARCH DESIGN AND METHODS: A semistructured focus group interview was conducted with 53 participants with T2DM. Participants were purposefully sampled and asked to share their perspective on Ramadan fasting. All interviews were audio recorded, transcribed verbatim and analyzed thematically.
    RESULTS: Participants reported optimism towards fasting during Ramadan, as they believed that fasting was beneficial to their overall well-being, and a time for family bonding. Most participants made limited attempts to discuss with their doctors on the decision to fast and self-adjusted their medication based on experience and symptoms during this period. They also reported difficulty in managing their diet, due to fear of hypoglycemia and the collective social aspect of fasting.
    CONCLUSION: Muslims are optimistic about their well-being when fasting during Ramadan. Many choose to fulfill their religious obligation despite being discouraged by their doctors. Collaboration with religious authorities should be explored to ensure patients receive adequate education before fasting during Ramadan.
    TRIAL REGISTRATION NUMBER: NCT02189135; Results.
  18. Nugroho AE, Zhang W, Hirasawa Y, Tang Y, Wong CP, Kaneda T, et al.
    J Nat Prod, 2018 11 26;81(11):2600-2604.
    PMID: 30362746 DOI: 10.1021/acs.jnatprod.8b00749
    Three new bisindole alkaloids, bisleuconothines B-D (1-3), were isolated from the bark of Leuconotis griffithii. Their structures were elucidated by 1D and 2D NMR spectroscopy and DFT calculations. Bisleuconothine B (1) is the first monoterpene indole alkaloid dimer featuring bridges between both C-16-C-10' and C-2-O-C-9'. All compounds were deemed noncytotoxic (IC50 > 10 μM) when tested against A549 human lung adenocarcinoma cells.
  19. Yap YY, Wong CP, Lee KS, Ming LC, Khan TM
    Ther Innov Regul Sci, 2017 Jul;51(4):446-459.
    PMID: 30227055 DOI: 10.1177/2168479017697253
    This article aims to discuss the main consequences of the implementation of the Trans-Pacific Partnership Agreement (TTPA) in the pharmaceutical sector in regard to public health, focusing on the accessibility and affordability of medicines. This paper also looks at the likely impact of the TPP agreement on access to affordable medicines. The potential effects of provisions in the final text are explored based on the context of developed and developing countries. A meta-synthesis study design was used. The thematic analysis technique was used to generate themes and a decision tree of the TTPA meta-synthesis. PubMed, EBSCOhost, Ovid, and Scopus databases from inception until the first week of January 2016 were used. Only peer-reviewed journals that discussed TPPA's impact on the pharmaceutical sector were included. Data were extracted by 2 reviewers and then verified by 3 senior researchers. The extracted data were imported into Excel spreadsheets and coded line by line. Codes were organized into descriptive themes. The identified themes were cross-checked against original articles to ensure consistency. A total of 85 full articles and reports were reviewed and, finally, 32 of them were used in the meta-synthesis. Two central themes to the TTPA emerged: intellectual property rights and transparency. Five subthemes were identified under intellectual property rights: patent subject matter (representing scope of patentability), patent term adjustment for patent office delays (representing patent term extension), protection of undisclosed test or other data (representing data exclusivity), protection of undisclosed test or other data (representing patent linkage), and compulsory licensing. Meanwhile, transparency and anti-corruption-procedural fairness, which presents restriction of coverage program and reimbursement, were identified as the subthemes of transparency. Findings indicate that the TPPA could potentially hinder the affordability and accessibility of medicine, which could increase risks to public health.
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