Displaying publications 41 - 60 of 194 in total

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  1. Gan SH, Ismail R, Wan Adnan WA, Zulmi W
    Mol Diagn Ther, 2007;11(3):171-81.
    PMID: 17570739
    Tramadol is metabolized by the highly polymorphic enzyme cytochrome P450 (CYP)2D6. Patients with different CYP2D6 genotypes may respond differently to tramadol in terms of pain relief and adverse events. In this study, we compare the pharmacokinetics and effects of tramadol in Malaysian patients with different genotypes to establish the pharmacokinetic-pharmacodynamic relationship of tramadol.
  2. Gan SH, Ismail R, Wan Adnan WA, Zulmi W, Jelliffe RW
    J Clin Pharm Ther, 2004 Oct;29(5):455-63.
    PMID: 15482390
    Although the kinetic behaviour of tramadol has been described, the present study is the first to our knowledge, to report specifically on the population pharmacokinetic modelling of tramadol hydrochloride.
  3. Gan SH, Ismail R, Wan Adnan WA, Wan Z
    J Pharm Biomed Anal, 2002 Sep 05;30(2):189-195.
    PMID: 12191703
    The aim of the present study is to investigate the influence of the CYP2D6*10 allele on the disposition of tramadol hydrochloride in Malaysian subjects. A single dose of 100 mg tramadol was given intravenously to 30 healthy orthopaedic patients undergoing various elective surgeries. After having obtained written informed consents, patients were genotyped for CYP2D6*10: the most common CYP2D6 allele among Asians by means of allele-specific polymerase chain reaction. The presence of other mutations (CYP2D6*1, *3, *4, *5, *9 and *17) was also investigated. Tramadol was extracted from 1 ml serum with an n-hexane: ethylacetate combination (4:1) after alkalinisation with ammonia (pH 10.6). Serum concentrations were measured by means of high-performance liquid chromatography. The pharmacokinetics of tramadol was studied during the 24 h after the dose. As among other Asians, the allele frequency for CYP2D6*10 among Malaysians was high (0.43). Subjects who were homozygous for CYP2D6*10 had significantly (P=0.046) longer mean serum half-life of tramadol than subjects of the normal or the heterozygous group (Kruskal-Wallis test). When patients were screened for the presence of other alleles, the pharmacokinetic parameter values were better explained. CYP2D6 activity may play a main role in determining tramadol pharmacokinetics. The CYP2D6*10 allele particularly was associated with higher serum levels of tramadol compared with the CYP2D6*1 allele. However, genotyping for CYP2D6*10 alone is not sufficient to explain tramadol disposition.
  4. 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.
  5. Gan SH, Ismail R, Wan Adnan WA, Zulmi W, Kumaraswamy N, Larmie ET
    Br J Clin Pharmacol, 2004 Jun;57(6):785-9.
    PMID: 15151524
    A person with Type A personality is an 'aggressor' compared with the rarely harried Type B. Although debrisoquine hydroxylase (CYP2D6) capacity has been associated with personality, no study has specifically investigated its association with personality Type A and B. Therefore the aim of this research was to study the impact of CYP2D6 on Type A and B personality.
  6. Gan SH, Ismail R, Wan Adnan WA, Wan Z
    Clin Chim Acta, 2003 Mar;329(1-2):61-8.
    PMID: 12589966 DOI: 10.1016/s0009-8981(03)00019-6
    BACKGROUND: Hair roots provide a useful alternative to blood as a source of DNA for genotyping. Besides simple and non-invasive collections, the DNA extraction step is also easy to perform and is fast. The aim of our study is to determine if hair roots can be used to genotype all of the common CYP2D6 alleles for routine screening purposes.

    METHOD: The study complies with the Declaration of Helsinki. After obtaining informed consents, both blood and hair samples were collected from 92 patients for genotyping of the CYP2D6 gene. PCR was used to detect the following mutations: CYP2D6*1, *3, *4, *5, *9, *10, *17 and duplication gene. The results were compared where hair roots and blood were used as templates for DNA respectively.

    RESULTS: When blood was used as a source of DNA for genotyping, all of the investigated CYP2D6 alleles were successfully amplified. However, with hair roots, the genes with the larger fragment sizes: CYP2D6*5 and the duplication gene could not be amplified and the bands of other alleles investigated were faint when visualized under UV light.

    CONCLUSIONS: DNA extraction from hair roots and leucocytes yielded similar results but the DNA extracted from hair roots did not allow successful amplification of the longer genes such as the CYP2D6*5 and the duplication gene.
  7. Gan SH, Ismail R, Wan Adnan WA, Wan Z
    PMID: 12016023
    An HPLC system using a simple liquid-liquid extraction and HPLC with UV detection has been validated to determine tramadol concentration in human plasma. The method developed was selective and linear for concentrations ranging from 10 to 2000 ng/ml with average recovery of 98.63%. The limit of quantitation (LOQ) was 10 ng/ml and the percentage recovery of the internal standard phenacetin was 76.51%. The intra-day accuracy ranged from 87.55 to 105.99% and the inter-day accuracy, 93.44 to 98.43% for tramadol. Good precision (5.32 and 6.67% for intra- and inter-day, respectively) was obtained at LOQ. The method has been applied to determine tramadol concentrations in human plasma samples for a pharmacokinetic study.
  8. Ghagane SC, Puranik SI, Gan SH, Hiremath MB, Nerli RB, Ravishankar MV
    Hum Antibodies, 2017;26(3):135-142.
    PMID: 29060935 DOI: 10.3233/HAB-170331
    With the flourishing of innovation in drug discovery into a new era of personalized therapy, the use of monoclonal antibodies (mAbs) in the treatment of various ailments lies at the forefront. Major improvements in genetic sequencing and biomedical techniques as well as research into mAbs emphasize on determining new targets for advanced therapy while maximizing efficacy for clinical application. However, a balance has to be achieved concerning developing a target with low toxicity combined with high specificity and versatility, to allow a specific antibody to facilitate several biotic effects, ranging from neutralization of virus mechanisms to modulation of immune response and maintaining low global economic cost. Presently, there are approximately 30 mAbs' permitted for therapeutic use with many more being tested in clinical trials. Nevertheless, the heavy cost of mAbs' production, stowage and management as well as the subsequent hindrances to their development are outweighed by mAbs' clinical advantages. Compared to conventional drugs, since mAbs use as pharmacologic iotas have specific physical features and modes of action, they should be considered as a discrete therapeutic category. In this review, the history of mAb generation and the innovative technological applications of mAbs that has advanced in clinical practices is reviewed.
  9. Guad RM, Taylor-Robinson AW, Wu YS, Gan SH, Zaharan NL, Basu RC, et al.
    BMC Nephrol, 2020 09 07;21(1):388.
    PMID: 32894076 DOI: 10.1186/s12882-020-02052-9
    BACKGROUND: New-onset diabetes after transplantation (NODAT) is associated with reduced patient and graft survival. This study examined the clinical and selected genetic factors associated with NODAT among renal-transplanted Malaysian patients.

    METHODS: This study included 168 non-diabetic patients (58% males, 69% of Chinese ethnicity) who received renal transplantation between 1st January 1994 to 31st December 2014, and were followed up in two major renal transplant centres in Malaysia. Fasting blood glucose levels were used to diagnose NODAT in patients who received renal transplantation within 1 year. Two single nucleotide polymorphisms (SNPs), namely; rs1494558 (interleukin-7 receptor, IL-7R) and rs2232365 (mannose-binding leptin-2, MBL2) were selected and genotyped using Sequenom MassArray platform. Cox proportional hazard regression analyses were used to examine the risk of developing NODAT according to the different demographics and clinical covariates, utilizing four time-points (one-month, three-months, six-months, one-year) post-transplant.

    RESULTS: Seventeen per cent of patients (n = 29, 55% males, 69% Chinese) were found to have developed NODAT within one-year of renal transplantation based on their fasting blood glucose levels. NODAT patients had renal transplantation at an older age compared to non-NODAT (39.3 ± 13.4 vs 33.9 ± 11.8 years, p = 0.03). In multivariate analysis, renal-transplanted patients who received a higher daily dose of cyclosporine (mg) were associated with increased risk of NODAT (Hazard ratio (HR) =1.01 per mg increase in dose, 95% confidence interval (CI) 1.00-1.01, p = 0.002). Other demographic (gender, ethnicities, age at transplant) and clinical factors (primary kidney disease, type of donor, place of transplant, type of calcineurin inhibitors, duration of dialysis pre-transplant, BMI, creatinine levels, and daily doses of tacrolimus and prednisolone) were not found to be significantly associated with risk of NODAT. GA genotype of rs1494558 (HR = 3.15 95% CI 1.26, 7.86) and AG genotype of rs2232365 (HR = 2.57 95% CI 1.07, 6.18) were associated with increased risk of NODAT as compared to AA genotypes.

    CONCLUSION: The daily dose of cyclosporine and SNPs of IL-7R (rs1494558) and MBL2 (rs2232365) genes are significantly associated with the development of NODAT in the Malaysian renal transplant population.

  10. Haque ST, Islam RA, Gan SH, Chowdhury EH
    Int J Mol Sci, 2020 Sep 14;21(18).
    PMID: 32937817 DOI: 10.3390/ijms21186721
    Background: The limitations of conventional treatment modalities in cancer, especially in breast cancer, facilitated the necessity for developing a safer drug delivery system (DDS). Inorganic nano-carriers based on calcium phosphates such as hydroxyapatite (HA) and carbonate apatite (CA) have gained attention due to their biocompatibility, reduced toxicity, and improved therapeutic efficacy. Methods: In this study, the potential of goose bone ash (GBA), a natural derivative of HA or CA, was exploited as a pH-responsive carrier to successfully deliver doxorubicin (DOX), an anthracycline drug into breast cancer cells (e.g., MCF-7 and MDA-MB-231 cells). GBA in either pristine form or in suspension was characterized in terms of size, morphology, functional groups, cellular internalization, cytotoxicity, pH-responsive drug (DOX) release, and protein corona analysis. Results: The pH-responsive drug release study demonstrated the prompt release of DOX from GBA through its disintegration in acidic pH (5.5-6.5), which mimics the pH of the endosomal and lysosomal compartments as well as the stability of GBA in physiological pH (pH 7.5). The result of DOX binding with GBA indicated an increment in binding affinity with increasing concentrations of DOX. Cell viability and cytotoxicity analysis showed no innate toxicity of GBA particles. Both qualitative and quantitative cellular uptake analysis in both cell lines displayed an enhanced cellular internalization of DOX-loaded GBA compared to free DOX molecules. The protein corona spontaneously formed on the surface of GBA particles exhibited its affinity toward transport proteins, structural proteins, and a few other selective proteins. The adsorption of transport proteins could extend the circulation half-life in biological environment and increase the accumulation of the drug-loaded NPs through the enhanced permeability and retention (EPR) effect at the tumor site. Conclusion: These findings highlight the potential of GBA as a DDS to successfully deliver therapeutics into breast cancer cells.
  11. Hizan NS, Hassan NHM, Haron J, Abubakar MB, Mahdi NMN, Gan SH
    Integr Med Res, 2018 Dec;7(4):322-327.
    PMID: 30591885 DOI: 10.1016/j.imr.2018.07.002
    Background: To investigate whether the combination of anastrozole and Tualang honey (T honey) influences background parenchymal enhancement (BPE) in breast magnetic resonance imaging (MRI) of postmenopausal women with breast cancer.

    Methods: A total of 30 patients were recruited and randomly divided into control (anastrozole 1 mg daily) and intervention (anastrozole 1 mg + T honey 20 g daily). The BPE of the contralateral breast before and six months following treatment was compared using the sign test.

    Results: There was a decrease in BPE in 10% of the women (p = 0.317) who received only anastrozole, which resulted in a change of BPE category from moderate to mild. However, the combination of anastrozole and T honey evoked a decrease in BPE in 42% of the patients (p = 0.034).

    Conclusions: The combination of T honey and anastrozole maybe more efficacious than anastrozole alone in decreasing breast BPE in breast cancer patients. These findings support the medicinal value of T honey as an adjuvant treatment to anastrozole.

  12. Hossen MS, Ali MY, Jahurul MHA, Abdel-Daim MM, Gan SH, Khalil MI
    Pharmacol Rep, 2017 Dec;69(6):1194-1205.
    PMID: 29128800 DOI: 10.1016/j.pharep.2017.07.002
    Honey contains many active constituents and antioxidants such as polyphenols. Polyphenols are phytochemicals, a generic term for the several thousand plant-based molecules with antioxidant properties. Many in vitro studies in human cell cultures as well as many animal studies confirm the protective effect of polyphenols on a number of diseases such as cardiovascular diseases (CVD), diabetes, cancer, neurodegenerative diseases, pulmonary diseases, liver diseases and so on. Nevertheless, it is challenging to identify the specific biological mechanism underlying individual polyphenols and to determine how polyphenols impact human health. To date, several studies have attempted to elucidate the molecular pathway for specific polyphenols acting against particular diseases. In this review, we report on the various polyphenols present in different types of honey according to their classification, source, and specific functions and discuss several of the honey polyphenols with the most therapeutic potential to exert an effect on the various pathologies of some major diseases including CVD, diabetes, cancer, and neurodegenerative diseases.
  13. Hossen MS, Tanvir EM, Prince MB, Paul S, Saha M, Ali MY, et al.
    Pharm Biol, 2017 Dec;55(1):1937-1945.
    PMID: 28675957 DOI: 10.1080/13880209.2017.1345951
    CONTEXT: Turmeric (Curcuma longa L. [Zingiberaceae]) is used in the treatment of a variety of conditions including pesticide-induced toxicity.

    OBJECTIVE: The study reports the antioxidant properties and the protective effects of turmeric against carbofuran (CF)-induced toxicity in rats.

    MATERIALS AND METHODS: The antioxidant potential was determined by using free radicals scavenging activity and ferric reducing antioxidant power values. Male Wistar rats were randomly divided into four groups, designated as control, turmeric (100 mg/kg/day), CF (1 mg/kg/day) and turmeric (100 mg/kg/day) + CF (1 mg/kg/day) treatments. All of the doses were administered orally for 28 consecutive days. The biological activity of the turmeric and CF was determined by using several standard biochemical methods.

    RESULTS: Turmeric contains high concentrations of polyphenols (8.97 ± 0.15 g GAEs), flavonoids (5.46 ± 0.29 g CEs), ascorbic acid (0.06 ± 0.00 mg AEs) and FRAP value (1972.66 ± 104.78 μM Fe2+) per 100 g of sample. Oral administration of CF caused significant changes in some of the blood indices, such as, mean corpuscular volume, corpuscular hemoglobin, white blood cell, platelet distribution width and induced severe hepatic injuries associated with oxidative stress, as observed by the significantly higher lipid peroxidation (LPO) levels when compared to control, while the activities of cellular antioxidant enzymes (including superoxide dismutase and glutathione peroxidase) were significantly suppressed in the liver tissue.

    DISCUSSION AND CONCLUSION: Turmeric supplementation could protect against CF-induced hematological perturbations and hepatic injuries in rats, plausibly by the up-regulation of antioxidant enzymes and inhibition of LPO to confer the protective effect.

  14. Hossen MS, Billah Prince MM, Tanvir EM, Chowdhury MAZ, Rahman MA, Alam F, et al.
    PMID: 29861774 DOI: 10.1155/2018/6254929
    The current study aimed to investigate the ameliorative effects of two types of mushrooms, Ganoderma lucidum (GL) and Auricularia polytricha (AP), against carbofuran- (CF) induced toxicity in rats. Male Wistar rats (n = 42) were divided into six equal groups. The rats in the negative control group received oral administration of CF at 1 mg/kg with the normal diet for 28 days. The treatment groups received oral administration of ethanolic extract of GL or AP at 100 mg/kg followed by coadministration of CF at 1 mg/kg with the normal diet for the same experimental period, respectively. In the CF alone treated group, there were significant decreases in the erythrocytic and thrombocytic indices but increases in the concentrations of the total leukocytes, including the agranulocytes. A significant increase in all of the liver function biomarkers except albumin, in lipid profiles except high-density lipoprotein, and in the kidney function markers occurred in the negative control group compared to the rats of the normal control and positive control groups. The coadministration of mushroom extracts significantly ameliorated the toxic effects of the CF. The GL mushroom extract was more efficacious than that of the AP mushroom, possibly due to the presence of high levels of phenolic compounds and other antioxidants in the GL mushroom.
  15. Husin F, Chan YY, Gan SH, Sulaiman SA, Shueb RH
    PMID: 25767554 DOI: 10.1155/2015/596109
    Objective. To investigate the potential effect of Hydrocotyle sibthorpioides Lam. (H. sibthorpioides) extracts against in vitro dengue viral replication. Methods. The cytotoxicity of H. sibthorpioides was evaluated using a cell viability assay. Cells were pre- and posttreated with water and methanol extracts of H. sibthorpioides, and the viral inhibitory effect was investigated by observing the morphological changes, which were further confirmed by plaque assay. Results. The methanolic extract cytotoxicity was higher in Vero and C6/36 cells than the cytotoxicity of the water extract. Preincubation of the cells with H. sibthorpioides extract showed nonexistent to mild prophylactic effects. The posttreatment of Vero cells with H. sibthorpioides methanolic extract presented higher antidengue activities when compared with the water extract. Surprisingly, posttreatment of C6/36 cells resulted in an enhancement of viral replication. Conclusion. H. sibthorpioides had variable effects on dengue viral replication, depending on the treatment, cell lines, and solvent types. This study provides important novel insights on the phytomedicinal properties of H. sibthorpioides extracts on dengue virus.
  16. Islam A, Khalil I, Islam N, Moniruzzaman M, Mottalib A, Sulaiman SA, et al.
    PMID: 23043497 DOI: 10.1186/1472-6882-12-177
    There is no available information on physicochemical and antioxidant properties on Bangladeshi honey. We investigated five different monofloral and three different multifloral honey samples collected from different parts of Bangladesh.
  17. Islam MA, Alam F, Khalil MI, Sasongko TH, Gan SH
    Curr Pharm Des, 2016;22(20):2926-46.
    PMID: 26951101
    Globally, thrombosis-associated disorders are one of the main contributors to fatalities. Besides genetic influences, there are some acquired and environmental risk factors dominating thrombotic diseases. Although standard regimens have been used for a long time, many side effects still occur which can be life threatening. Therefore, natural products are good alternatives. Although the quest for antithrombotic natural products came to light only since the end of last century, in the last two decades, a considerable number of natural products showing antithrombotic activities (antiplatelet, anticoagulant and fibrinolytic) with no or minimal side effects have been reported. In this review, several natural products used as antithrombotic agents including medicinal plants, vegetables, fruits, spices and edible mushrooms which have been discovered in the last 15 years and their target sites (thrombogenic components, factors and thrombotic pathways) are described. In addition, the side effects, limitations and interactions of standard regimens with natural products are also discussed. The active compounds could serve as potential sources for future research on antithrombotic drug development. As a future direction, more advanced researches (in quest of the target cofactor or component involved in antithrombotic pathways) are warranted for the development of potential natural antithrombotic medications (alone or combined with standard regimens) to ensure maximum safety and efficacy.
  18. Islam MA, Alam F, Sasongko TH, Gan SH
    Curr Pharm Des, 2016;22(28):4451-69.
    PMID: 27229722
    Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by a persistently high titer of antiphospholipid antibodies (aPLs). In addition to pregnancy morbidity, arterial and/or venous thrombosis is another clinical feature of APS. Regardless of the type of APS, the thrombi formed by the induction of aPLs can lead to deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke and gangrene. Although the concept of APS was introduced approximately 32 years ago, its thrombogenic pathophysiology is still unclear. Therefore, patients are treated with anticoagulant and/or antiplatelet regimens just as in other thrombotic disorders even though the thrombotic pathophysiology is mainly aPLs-mediated. In this review, we provided an update of the cellular, auto-immune and genetic factors known to play important roles in the generation of thrombi. Current successful regimens are also outlined along with potential emerging treatment strategies that may lead to the optimum management of thrombotic APS patients.
  19. Islam MA, Wong KK, Sasongko TH, Gan SH, Wong JS
    Eur J Rheumatol, 2016 Sep;3(3):139-141.
    PMID: 27733946 DOI: 10.5152/eurjrheum.2015.0068
    Here we present a case report of three familial primary antiphospholipid syndrome (PAPS) patients from Malaysia. The three familial patients comprised two females and one male with a mean age of 26.3 years. The first diagnosis was made between 2005 and 2009, and all patients demonstrated deep vein thrombosis, high levels of IgM and IgG anticardiolipin antibodies, and received warfarin treatment international normalized ratio (INR) 2.0-3.0. The patients ceased to show clinical symptoms after treatment. Recently (August 2014), we investigated whether the levels of antiphospholipid antibodies remained elevated, and we found that seronegativity occurred in the patients. We suspect that prolonged anticoagulant treatment might be one of the causes of reduced levels of antiphospholipid antibodies in these familial PAPS patients.
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