Displaying publications 1 - 20 of 150 in total

  1. Yusof W, Gan SH
    Clin. Chim. Acta, 2009 May;403(1-2):105-9.
    PMID: 19361454 DOI: 10.1016/j.cca.2009.01.032
    CYP2A6 gene encodes the principal enzyme involved in the metabolism of many drugs including artesunate. We developed a simplified duplex nested PCR method for the detection of the CYP2A61B, CYP2A62, CYP2A64, CYP2A67, CYP2A68 and CYP2A69 variant alleles highly prevalent among Malaysian population.
  2. Gan SH, Ismail R
    J. Chromatogr. B Biomed. Sci. Appl., 2001 Aug 15;759(2):325-35.
    PMID: 11499486
    An HPLC system using solid-phase extraction and HPLC with UV detection has been validated in order to determine tramadol and o-desmethyltramadol (M1) concentrations in human plasma. The method developed was selective and linear for concentrations ranging from 50 to 3,500 ng/ml (tramadol) and 50 to 500 ng/ml (M1) with mean recoveries of 94.36 +/- 12.53% and 93.52 +/- 7.88%, respectively. Limit of quantitation (LOQ) was 50 ng/ml. For tramadol, the intra-day accuracy ranged from 95.48 to 114.64% and the inter-day accuracy, 97.21 to 103.24%. Good precision (0.51 and 18.32% for intra- and inter-day, respectively) was obtained at LOQ. The system has been applied to determine tramadol concentrations in human plasma samples for a pharmacokinetic study.
  3. Rao PV, Gan SH
    Curr Drug Metab, 2015;16(5):371-5.
    PMID: 25429672 DOI: 10.2174/1389200215666141125120215
    Nanotechnology is a field encompassing nanostructures, nanomaterials and nanoparticles, which are of increasing importance to researchers and industrial players alike. Nanotechnology addresses the construction and consumption of substances and devices on the nanometer scale. Nanomedicine is a new field that combines nanotechnology with medicine to boost human health care. Nanomedicine is an interdisciplinary field that includes various areas of biology, chemistry, physics and engineering. The most important problems related to diabetes management, such as self-monitoring of blood glucose levels and insulin injections, can now be conquered due to progress in nanomedicine, which offers glucose nanosensors, the layer-by-layer technique, carbon nanotubes, quantum dots, oral insulins, microspheres, artificial pancreases and nanopumps. In this review, the key methodological and scientific characteristics of nanomedicine related to diabetes treatment, glucose monitoring and insulin administration are discussed.
  4. Rao PV, Gan SH
    PMID: 24817901 DOI: 10.1155/2014/642942
    Cinnamon (Cinnamomum zeylanicum, and Cinnamon cassia), the eternal tree of tropical medicine, belongs to the Lauraceae family. Cinnamon is one of the most important spices used daily by people all over the world. Cinnamon primarily contains vital oils and other derivatives, such as cinnamaldehyde, cinnamic acid, and cinnamate. In addition to being an antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancer, lipid-lowering, and cardiovascular-disease-lowering compound, cinnamon has also been reported to have activities against neurological disorders, such as Parkinson's and Alzheimer's diseases. This review illustrates the pharmacological prospective of cinnamon and its use in daily life.
  5. Loo KW, Gan SH
    Gene, 2014 Jul 15;545(1):1-4.
    PMID: 24815047 DOI: 10.1016/j.gene.2014.05.016
    The Kelantanese Malays who resided in the remote northeastern regions of the Malay Peninsula in the Kelantan state are believed to have a unique genetic signature. The objective of this review is to analyze the populational sub-structure of the Kelantanese Malays from historical, genetic and linguistic perspectives. Historical data suggest that the Semang were composed of the Jahai, Bateq and Kensiu sub-tribes, whereas the Senoi were composed of only the Temiar sub-tribe. The Mendriq sub-tribe is believed to be the first group of aborigines to land in Kelantan. Subsequently, genetic analysis showed that the Kelantanese Malays are an independent clade at the base of the phylogenetic tree and contain genetic material similar to that of the Semang, specifically the Jahai and the Kensiu sub-tribes. The genetic data are supported by the fact that the Aslian language, a branch of the Austroasiatic languages that is widely spoken by the Semang, was potentially transmitted through agricultural activities. However, the potential limitation of this mini-review is the lack of primary reliable sources covering the historical, linguistic and genetic features of the Kelantanese Malays.
  6. Shaik MM, Gan SH
    Indian J Pharmacol, 2013 Mar-Apr;45(2):159-67.
    PMID: 23716893 DOI: 10.4103/0253-7613.108303
    Hyperhomocysteinemia and vitamins B(6), B(9), and B(12) deficiencies usually result in various neurological, vascular, ocular, renal, and pulmonary abnormalities. However, to date, there are no simultaneous detection methods available for determining homocysteine, vitamins B(6), B(9), and B(12) levels in various biological fluids. In this study, we aim to develop a new validated simultaneous detection method for all four compounds to save both cost and time of analysis.
  7. Loo KW, Gan SH
    Int J Stroke, 2013 Jun;8(4):273-5.
    PMID: 22974070 DOI: 10.1111/j.1747-4949.2012.00884.x
    In the Lao People's Democratic Republic (Laos), stroke is ranked as the third leading cause of death, with a 9·01% mortality rate. To date, neither the prevalence nor the incidence of stroke has been recorded in Laos. This omission may be attributed to a lack of awareness among Laotians of the signs and symptoms of stroke, incomplete data, or insufficient database recording. The only risk factor for stroke that has been studied extensively is cigarette smoking; studies have found that smokers have twice the risk of stroke. Unfortunately, smoking is increasing among youths, adults, and even healthcare professionals. The Southeast Asia Tobacco Control Alliance stated that 42% of hospitalized stroke patients are smokers. Laos is one of the least developed countries in the world, and the country has only one fully trained neurologist for the growing number of stroke cases. The Laos government should seek help from international bodies, such as the World Health Organization, to monitor and rehabilitate stroke patients and prevent stroke occurrence and recurrence.
  8. Loo KW, Gan SH
    Int J Stroke, 2013 Aug;8(6):475-8.
    PMID: 22973861 DOI: 10.1111/j.1747-4949.2012.00868.x
    In Cambodia, stroke is not ranked among the top 10 leading causes of death, but infectious disease are among the top three leading causes of death. This finding could be attributed to a lack of awareness among Cambodians of the signs and symptoms of stroke or to poor reporting, incomplete data, lack of neurologists and neurosurgeons, or low accessibility to the hospitals. The only study of stroke in Cambodia is the Prevalence of Non-Communicable Disease Risk Factors in Cambodia survey, which identified several stroke-related risk factors in the population. Tobacco chewing or smoking is the main risk factor for stroke in Cambodia. Traditional therapies, such as oyt pleung (moxibustion) and jup (cupping), are widely practiced for stroke rehabilitation. In Cambodia, there are few neurologists and few important equipment, such as magnetic resonance imaging machines and computed tomography scanners. The Cambodian government should cooperate with the World Health Organization and the United Nations Children's Fund to attract foreign expertise and technologies to treat stroke patients.
  9. Loo KW, Gan SH
    Int J Stroke, 2013 Feb;8(2):131-4.
    PMID: 22568853 DOI: 10.1111/j.1747-4949.2012.00806.x
    Based on disability-adjusted life-years, stroke is the second leading cause of death and among the top five diseases with the greatest burden. Although two community-based studies have been conducted to determine the prevalence of stroke in the Philippines, the incidence has not been nationally recorded to date. The prevalence ranged from 1·9% to 6·59%, and 'Wiihabilitation', a rehabilitation stroke therapy, is widely practiced. A clinical trial for stroke rehabilitation using the Chinese Medicine NeuroAid®, which consists of several herbs, is ongoing in many hospitals across the Philippines. Due to their ready availability, phytomedicines are widely used, especially in the rural areas, for the treatment of hypertension, diabetes mellitus, and hypercholesterolemia, which are predisposing factors for stroke in the Philippines. Due to the increasing number of stroke cases annually, the government of the Philippines should emphasize primary and secondary prevention strategies.
  10. Loo KW, Gan SH
    Int J Stroke, 2012 Feb;7(2):165-7.
    PMID: 22264370 DOI: 10.1111/j.1747-4949.2011.00767.x
    Stroke is one of the top five leading causes of death and one of the top 10 causes for hospitalization in Malaysia. Stroke is also in the top five diseases with the greatest burden of disease, based on disability-adjusted life years. However, prospective studies on stroke in Malaysia are limited. To date, neither the prevalence of stroke nor its incidence nationally has been recorded. Hypertension is the major risk factor for stroke. The mean age of stroke patients in Malaysia is between 54.5 and 62.6 years. Traditional medicine is commonly practiced. With the increasing number of stroke cases annually, more government and nongovernment organizations should be involved in primary and secondary prevention strategies.
  11. Ruzilawati AB, Gan SH
    Pharmacology, 2010;85(6):357-64.
    PMID: 20523106 DOI: 10.1159/000302731
    AIM: To investigate the effects of CYP3A4 and CYP2C8 enzymes on repaglinide's pharmacokinetics in healthy Malaysian subjects.

    METHODS: Subjects (n = 121) received oral repaglinide (4 mg). Blood samples were taken at 0, 30, 60, 120, 180 and 240 min and serum concentrations of repaglinide were determined using high-performance liquid chromatography. Subjects were also genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for CYP3A4*4, *5 and*18 and by an allele-specific multiplex PCR for CYP2C8*2, *3, *4 and *5 alleles.

    RESULTS: The allele frequencies of CYP2C8*1, *2, *3, *4 and *5 were 95.04, 0.40, 0.40, 0 and 4.13%, respectively. The frequencies of the CYP3A4*1, *4, *5 and *18 alleles were 97.93, 0, 0 and 2.07%, respectively. CYP2C8 and CYP3A4 genotypes were not significantly associated with repaglinide's blood glucose-lowering effect. However, the CYP3A4 genotype significantly influenced some of repaglinide's pharmacokinetics, where the mean elimination rate constant was 44.0% lower (p = 0.04) and the mean half-life was 33.8% higher (p = 0.04) in subjects with the CYP3A4*1/*18 genotype as compared to those with the normal CYP3A4*1/*1 genotype. This result confirms that CYP3A4 plays a large role in metabolizing repaglinide.

    CONCLUSION: Genetic polymorphisms of CYP3A4, specifically CYP3A4*18, play a major role in contributing to the interindividual variability in repaglinide's pharmacokinetics.

  12. Abubakar MB, Gan SH
    Oncology, 2016;91(1):3-12.
    PMID: 27233906 DOI: 10.1159/000446437
    The advent of advanced molecular targeted therapy has resulted in improved prognoses for patients with advanced malignancies. However, despite the significant success and specificity of this advocated targeted therapy, significant on- and off-target adverse effects and inter-individual variability in treatment responses have been reported. The interpatient variability in drug response has been suggested to be partly due to variations in patient genomes. Therefore, the identification of genetic biomarkers by conducting pharmacogenetics studies can help predict patient responses to targeted therapy and may serve as a basis for individualized treatment. In this review, both clinically established and potential molecular targets are highlighted. Overall, current literature suggests that individualization of targeted therapy is promising; however, integrating the clinical benefits of identified biomarkers into clinical practice for personalized medicine remains a major challenge, and further studies to validate these markers and identify novel therapeutic approaches are needed.
  13. Shaik MM, Gan SH
    Biomed Res Int, 2015;2015:469529.
    PMID: 25815319 DOI: 10.1155/2015/469529
    Migraine is the most common form of headache disorder globally. The etiology of migraine is multifactorial, with genetic components and environmental interactions considered to be the main causal factors. Some researchers postulate that deficits in mitochondrial energy reserves can cause migraine or an increase in homocysteine levels can lead to migraine attacks; therefore, vitamins could play a vital role in migraine prevention. For instance, riboflavin influences mitochondrial dysfunction and prevents migraine. Genes such as flavoenzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma levels of homocysteine and migraine with aura. Homocysteine catalyzation requires the presence of vitamins B6, B12, and folic acid, which can decrease the severity of migraine with aura, making these vitamins potentially useful prophylactic agents for treating migraine with aura. Menstrual migraine, on the other hand, is associated with increased prostaglandin (PG) levels in the endometrium, indicating a role for vitamin E, which is an anti-PG. Vitamin C can also be used as a scavenger of reactive oxygen species for treating neurogenic inflammation in migraine patients. This paper reviews possible therapies based on vitamin supplementation for migraine prophylaxis, focusing on migraine with aura and menstrual migraine.
  14. Abubakar MB, Gan SH
    Niger J Physiol Sci, 2017 Dec 30;32(2):219-225.
    PMID: 29485645
    Although anastrozole (Anas) plays a key role in the management of endocrine sensitive post-menopausal (PM) breast cancer (BC), there is much variability in its efficacy and tolerability. Anas-associated musculoskeletal symptoms (MS) and other adverse reactions, such as hot flashes (HF) and vaginal dryness/dyspareunia (VDD), are common and can affect the quality of life of BC patients, even sometimes leading to treatment withdrawal. The aim of this study was to determine the clinical and demographic factors associated with these adverse events. This is a cross-sectional study in estrogen receptor (ER) positive PM women (n = 92) with stages I to III BC receiving Anas. Multivariate analyses were performed to investigate the factors associated with Anas-induced adverse effects such as MS, HF and VDD. A serum estradiol concentration was undetectable (< 36.7 pmol/L) in 68.1% of patients but was detectable within a normal range (>36.7-88.1 pmol/L) in the other 31.9% of patients, and this group was found to have a lower odds of having at least one adverse effect (AE) compared to those with undetectable levels [adjusted odds ratio (AOR) 0.12, 95% confidence interval (CI) 0.02 to 0.64, p = 0.013]. Women with grades II and III tumors and a family history of BC had a higher odds of AE (grade II: AOR 12.22, CI 1.48 to 100.80, p = 0.020; grade III: AOR 12.95, CI 1.25 to 134.33, p = 0.032) and VDD (AOR 5.99, CI 1.30 to 27.52, p = 0.021), respectively. Patients who received Anas treatment for more than one year had a higher odds of VDD (one to three years: AOR 34.57, CI 3.86, 309.50, p = 0.002; more than 3 years: AOR 27.90, CI 2.21 to 351.84, p = 0.010). Advanced age also lowered the odds of HF (AOR 0.90, CI 0.83 to 1.00, p = 0.049). In conclusion, patients' hormonal environments and durations of Anas treatment may play a role in developing Anas-induced adverse effects.
  15. Abubakar MB, Wei K, Gan SH
    Pharmacogenet. Genomics, 2014 Dec;24(12):575-81.
    PMID: 25203739 DOI: 10.1097/FPC.0000000000000092
    Breast cancer is a common cause of cancer mortality among women. Several genetic factors have been implicated in its development. Current treatment guidelines for estrogen receptor-positive breast cancer recommend that anastrozole [or any of the other two aromatase inhibitors (letrozole and exemestane)] is used as an alternative to tamoxifen or following several years of tamoxifen treatment. Nevertheless, this approach is still associated with many challenges, ranging from the recurrence of breast cancer to considerable interindividual variability in the tolerability of anastrozole, which may cause adverse effects, such as musculoskeletal symptoms, and lead to the withdrawal of many patients from treatment. Variabilities in the genes encoding the drug target (aromatase) or its metabolizing enzymes (CYP3A and UGT1A) contribute toward the interindividual variability in anastrozole's pharmacokinetics and/or pharmacodynamics. This paper reviews the role of genetic polymorphisms of CYP19A1, CYP3A4, and UGT1A4 in the responses of female hormone receptor-positive postmenopausal breast cancer patients to anastrozole. Many reviews in the literature have suggested that the study of functional polymorphisms and investigation of relevant genetic markers may provide valuable information in predicting responses to anastrozole in terms of its therapeutic and adverse effects. Nevertheless, more studies are required before the knowledge of its pharmacogenomics can be applied to the individualization of treatment to ensure that patients receive the maximum benefits. Therefore, future analyses, including but not limited to genome-wide association studies, are encouraged to address some of the gray areas in the pharmacogenomics of anastrozole therapy in postmenopausal breast cancer cases; this will help in providing guidance for future pharmacogenomics protocols when anastrozole is utilized in patients' management.
  16. Loo KW, Griffiths LR, Gan SH
    J Diabetes, 2014 Sep;6(5):447.
    PMID: 24645716 DOI: 10.1111/1753-0407.12151
  17. Mijanur Rahman M, Gan SH, Khalil MI
    PMID: 24876885 DOI: 10.1155/2014/958721
    Honey is the only insect-derived natural product with therapeutic, traditional, spiritual, nutritional, cosmetic, and industrial value. In addition to having excellent nutritional value, honey is a good source of physiologically active natural compounds, such as polyphenols. Unfortunately, there are very few current research projects investigating the nootropic and neuropharmacological effects of honey, and these are still in their early stages. Raw honey possesses nootropic effects, such as memory-enhancing effects, as well as neuropharmacological activities, such as anxiolytic, antinociceptive, anticonvulsant, and antidepressant activities. Research suggests that the polyphenol constituents of honey can quench biological reactive oxygen species and counter oxidative stress while restoring the cellular antioxidant defense system. Honey polyphenols are also directly involved in apoptotic activities while attenuating microglia-induced neuroinflammation. Honey polyphenols are useful in improving memory deficits and can act at the molecular level. Therefore, the ultimate biochemical impact of honey on specific neurodegenerative diseases, apoptosis, necrosis, neuroinflammation, synaptic plasticity, and behavior-modulating neural circuitry should be evaluated with appropriate mechanistic approaches using biochemical and molecular tools.
  18. Shaik MM, Gan SH, Kamal MA
    CNS Neurol Disord Drug Targets, 2014 Mar;13(2):283-9.
    PMID: 24074446
    Cognitive decline is a debilitating feature of Alzheimer's disease (AD). The causes leading to such impairment are still poorly understood and effective treatments for AD are still unavailable. Type 2 diabetes mellitus (T2DM) has been identified as a risk factor for AD due to desensitisation of insulin receptors in the brain. Recent studies have suggested that epigenetic mechanisms may also play a pivotal role in the pathogenesis of both AD and T2DM. This article describes the correlation between AD and T2DM and provides the insights to the epigenetics of AD. Currently, more research is needed to clarify the exact role of epigenetic regulation in the course and development of AD and also in relation to insulin. Research conducted especially in the earlier stages of the disease could provide more insight into its underlying pathophysiology to help in early diagnosis and the development of more effective treatment strategies.
  19. Loo KW, Griffiths LR, Gan SH
    BMC Med. Genet., 2012;13:34.
    PMID: 22594584 DOI: 10.1186/1471-2350-13-34
    Hyperhomocysteinemia as a consequence of the MTHFR 677 C > T variant is associated with cardiovascular disease and stroke. Another factor that can potentially contribute to these disorders is a depleted nitric oxide level, which can be due to the presence of eNOS +894 G > T and eNOS -786 T > C variants that make an individual more susceptible to endothelial dysfunction. A number of genotyping methods have been developed to investigate these variants. However, simultaneous detection methods using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis are still lacking. In this study, a novel multiplex PCR-RFLP method for the simultaneous detection of MTHFR 677 C > T and eNOS +894 G > T and eNOS -786 T > C variants was developed. A total of 114 healthy Malay subjects were recruited. The MTHFR 677 C > T and eNOS +894 G > T and eNOS -786 T > C variants were genotyped using the novel multiplex PCR-RFLP and confirmed by DNA sequencing as well as snpBLAST. Allele frequencies of MTHFR 677 C > T and eNOS +894 G > T and eNOS -786 T > C were calculated using the Hardy Weinberg equation.
  20. Tan KL, Ankathil R, Gan SH
    J Chromatogr B Analyt Technol Biomed Life Sci, 2011 Nov 15;879(30):3583-91.
    PMID: 22000961 DOI: 10.1016/j.jchromb.2011.09.048
    We developed a simple and sensitive method for the simultaneous detection of imatinib mesylate (IM) and its active metabolite, N-desmethyl imatinib (M1), in human serum samples. Separation was successfully achieved using an Agilent(®) ZORBAX Eclipse plus C(18) reversed phase column (50 mm × 2.1 mm, i.d.; 1.8 μm) under isocratic mobile phase conditions consisting of acetonitrile: 0.02 M potassium dihydrogen phosphate with 0.2% triethylamine at pH 3 (25:75, v/v) and ultra-violet detection was achieved at 235 nm. Extraction of the target compounds was completed using 100% cold acetonitrile. Good linearities (r(2)>0.99) for both IM and M1 were achieved for the concentration ranges of 50-1800 ng/mL and 50-360 ng/mL, respectively. The detection limits were 20 ng/mL and 10 ng/mL for M1 and IM, respectively. The intra- and inter-day precisions were less than 1% with percent recoveries of more than 90%. The method was successfully applied to calculate the pharmacokinetic parameters of chronic myeloid leukemia patients receiving imatinib. The method is suitable to be routinely applied for determination of IM and M1 in serum.
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