Displaying publications 181 - 200 of 257 in total

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  1. Pan Y, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, Pook PC, et al.
    J Ethnopharmacol, 2011 Jan 27;133(2):881-7.
    PMID: 21093571 DOI: 10.1016/j.jep.2010.11.026
    Andrographis paniculata (AP), Centella asiatica (CA) and Orthosiphon stamineus (OS) are three popular herbs traditionally used worldwide. AP is known for the treatment of infections and diabetes and CA is good for wound healing and healthy skin while OS is usually consumed as tea to treat kidney and urinary disorders. Interaction of these herbs with human cytochrome P450 2C19 (CYP2C19), a major hepatic CYP isoform involved in metabolism of many clinical drugs has not been investigated to date.
  2. Ali MA, Bastian S, Ismail R, Choon TS, Ali S, Aubry A, et al.
    J Enzyme Inhib Med Chem, 2011 Dec;26(6):890-4.
    PMID: 21395486 DOI: 10.3109/14756366.2011.559945
    A series of pyrazoline derivatives were synthesized and in vitro activity against Mycobacterium tuberculosis H37Rv was carried out. Among the synthesized compounds, compounds (4d) and (4f) 4-aminophenyl-3-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone and 4-aminophenyl-6,7-dimethoxy-3-phenyl-2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone were found to be the most active agent against M. tuberculosis H37Rv with a minimum inhibitory concentration of 10 μg/mL.
  3. Ghani RA, Zainudin S, Ctkong N, Rahman AF, Wafa SR, Mohamad M, et al.
    Nephrology (Carlton), 2006 Oct;11(5):386-93.
    PMID: 17014550
    Sepsis is characterized by an uncontrolled release of pro-inflammatory and anti-inflammatory mediators leading to immunoparalysis, cellular and humoral dysfunction, multiorgan dysfunction and death. This study evaluated the efficacy of high-volume haemofiltration (HVHF) compared with continuous venovenous haemofiltration (CVVH) in removing these inflammatory mediators. Clinical responses were assessed with the sequential organ failure assessment (SOFA) score.
  4. Zahari Z, Lee CS, Ibrahim MA, Musa N, Yasin MA, Lee YY, et al.
    Pain Ther, 2015 Dec;4(2):179-96.
    PMID: 26581429 DOI: 10.1007/s40122-015-0041-y
    We recently reported that a majority of opioid-dependent Malay males on methadone therapy are cold pain sensitive. It is postulated that common OPRM1 polymorphisms may be responsible. This study investigated the association between 118A>G (dbSNP rs1799971) and IVS2+691G>C (dbSNP rs2075572) variants on cold pain responses among opioid-dependent Malay males on methadone maintenance therapy.
  5. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    J Pharm Pharm Sci, 2016;19(1):127-36.
    PMID: 27096697 DOI: 10.18433/J3NS49
    PURPOSE: This study compared pain sensitivity among opioid dependent patients on methadone maintenance therapy (MMT) and opioid naive subjects.

    METHODS: The three hundred participants comprised 152 opioid naive subjects and 148 opioid dependent patients. Opioid naive subjects had not taken any opioids including morphine and methadone to their best knowledge and were presumed so after two consecutive negative urine screenings for drugs. All opioid dependent patients were stabilized in treatment, defined as having been enrolled in the program for more than one month with no change of methadone dosage over the past one month. Excluded from the study were individuals with chronic or ongoing acute pain and individuals with a history of analgesics ingestion within 3 d before the cold pressor test (CPT). Pain tolerance to CPT was evaluated at 0 h, and at 2, 4, 8, 12, and 24 h post-methadone dose.

    RESULTS: Patients exhibited a significantly shorter mean pain tolerance time of 34.17 s (95% CI 24.86, 43.49) versus 61.36 (52.23, 70.48) [p < 0.001] compared with opioid naive subjects. Time-dependent mean pain tolerance was also significantly different when naive subjects were compared to patients (p = 0.016).

    CONCLUSIONS: This study revealed hyperalgesia amongst patients on MMT, as manifested by their quicker hand withdrawal. The complaints of pain in this population should not be underestimated and the pain should be evaluated seriously and managed aggressively.

  6. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    Drug Alcohol Depend, 2016 08 01;165:143-50.
    PMID: 27289271 DOI: 10.1016/j.drugalcdep.2016.05.028
    BACKGROUND: CYP2B6 polymorphisms contribute to inter-individual variations in pharmacokinetics of methadone. Increased pain sensitivity is frequently reported by opioid dependent patients on methadone maintenance therapy (MMT). It is possible, therefore, that genetic polymorphisms in CYP2B6, which affects the metabolism of methadone, influence pain sensitivity among patients on MMT. This study investigated CYP2B6 polymorphisms and pain sensitivity in this group.

    METHODS: The cold pressor pain responses of 148 opioid dependent patients receiving MMT were evaluated using the cold pressor test (CPT). DNA was extracted from whole blood and subjected to polymerase chain reaction (PCR)-genotyping.

    RESULTS: Of the 148 subjects, 77 (52.0%) were carriers of CYP2B6*6 allele. CYP2B6*6 allele carriers had shorter cold pain threshold and pain tolerance times than non-carriers of CYP2B6*6 allele (21.05s vs 33.69s, p=0.036 and 27.15s vs 44.51s, p=0.020, respectively). Pain intensity scores of the CYP2B6*6 allele carriers was 67.55, whereas that of the CYP2B6*6 allele non-carriers was 64.86 (p=0.352).

    CONCLUSION: Our study indicates that the CYP2B6*6 allele is associated with a lower pain threshold and lower pain tolerance among males with opioid dependence on MMT. The CYP2B6*6 allele may provide a mechanistic explanation for clinical observations of heightened pain sensitivity among opioid dependent patients receiving MMT.

  7. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    Pain Ther, 2016 Jun;5(1):43-54.
    PMID: 26792136 DOI: 10.1007/s40122-016-0044-3
    INTRODUCTION: Methadone is a full agonist of the opioid receptor mu 1 which is encoded by the OPRM1 gene. Sleep disorders were frequently reported by opioid-dependent patients during methadone maintenance therapy (MMT). It is possible, therefore, that genetic polymorphisms in OPRM1 influence sleep quality among patients on MMT. This study investigated the association of OPRM1 polymorphisms with sleep quality among opioid-dependent patients on MMT.
    METHODS: The sleep quality of 165 male opioid-dependent patients receiving MMT was evaluated using the Pittsburgh Sleep Quality Index (PSQI). DNA was extracted from whole blood and subjected to polymerase chain reaction (PCR) genotyping.
    RESULTS: Patients with IVS2 + 691 CC genotype had higher PSQI scores [mean (SD) = 5.73 (2.89)] compared to those without the IVS2 + 691 CC genotype (IVS2 + 691 GG/GC genotype) [4.92 (2.31)], but the difference did not reach statistical significance (p = 0.081). Patients with combined 118 AA genotype and IVS2 + 691 GC genotype (AC/AG diplotype) had significantly lower PSQI scores [mean (SD) = 4.25 (2.27)] compared to those without the diplotype [5.68 (2.77)] (p = 0.018).
    CONCLUSION: Our study indicates that the AC/AG diplotype for the 118A>G and IVS2 + 691G>C polymorphisms of OPRM1 gene is associated with better sleep quality among males with opioid dependence on MMT.
    KEYWORDS: AC/AG diplotype; Male patients; Methadone; Methadone maintenance therapy; OPRM1; Opioid dependence; Opioid receptor; Opioid receptor, mu 1 gene; Pittsburgh Sleep Quality Index; Sleep quality
  8. Romaino SM, Teh LK, Zilfalil BA, Thong CP, Ismail AA, Amir J, et al.
    J Clin Pharm Ther, 2004 Feb;29(1):47-52.
    PMID: 14748897 DOI: 10.1046/j.1365-2710.2003.00535.x
    Polymorphism of the beta2-adrenergic receptor (beta2 AR) gene is an important determinant of the function of this receptor. It affects receptor down-regulation and beta2-agonist responses. It has also been a focus of interest in attempts to elucidate the genetic basis of asthma, hypertension, obesity and cystic fibrosis. Several different techniques have been established to determine beta2 AR genotypes but none of these methods are simple enough to detect simultaneously all the five alleles of our research interest (Arg16/Gly16, -20T/C, Gln27/Glu27, -47T/C and Thr164/Ile164).
  9. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S787-S803.
    PMID: 33828379 DOI: 10.4103/jpbs.JPBS_248_19
    Introduction: Dopamine receptor D2 (DRD2) is one of the dopamine receptors that have been studied in relation to opioid dependence. It is possible, therefore, that DRD2 gene (DRD2) polymorphisms influence treatment outcomes of patients with opioid dependence. The objective of this study was to investigate the influence of DRD2 polymorphisms on the clinical outcomes of opioid-dependent patients on methadone maintenance therapy (MMT).

    Materials and Methods: Patients with opioid dependence (n = 148) were recruited from MMT clinics. Pain sensitivity, severity of the opiate withdrawal syndrome, and sleep quality were assessed using cold pressor test (CPT), Subjective Opiate Withdrawal Scale (SOWS-M), and Pittsburgh Sleep Quality Index (PSQI)-Malay, respectively. Deoxyribonucleic acid (DNA) was extracted from whole blood, and then was used for genotyping of Val96Ala, Leu141Leu, Val154Ile, Pro310Ser, Ser311Cys, TaqI A, -141C Ins/Del, and A-241G polymorphisms.

    Results: Among 148 patients, 8.1% (n = 12), 60.8% (n = 90), 27.7% (n = 41), and 29.1% (n = 43) had at least one risk allele for Ser311Cys, TaqI A, -141C Ins/Del, and A-241G polymorphisms, respectively. There were no significant differences in pain responses (pain threshold, tolerance, and intensity), SOWS, and PSQI scores between DRD2 polymorphisms.

    Conclusion: The common DRD2 polymorphisms are not associated with pain sensitivity, severity of the opiate withdrawal syndrome, and sleep quality in patients with opioid dependence on MMT. However, this may be unique for Malays. Additional research should focus on investigating these findings in larger samples and different ethnicity.

  10. Sien PLM, Jamaludin NIA, Samrin SNA, S NS, Ismail R, Anuar Zaini A, et al.
    J Health Psychol, 2020 08;25(9):1310-1318.
    PMID: 31755316 DOI: 10.1177/1359105319890397
    Adolescents with type 1 diabetes mellitus are prone to have eating problems. This study aimed to determine factors of eating problems among this population in University Malaya Medical Centre. Fifteen adolescents who scored more than 20 marks in the Diabetes Eating Problem Survey - Revised questionnaire were invited for an in-depth interview. Questions were asked based on their questionnaire's response. The interview sessions were recorded, transcribed verbatim, and thematic analysis was used. Five main themes emerged: pressure, physiological factor, psychological factor, patient's low compliances to insulin intake and food control and fear. Early referral to child psychologist would prevent it from developing.
  11. Suresh Kumar R, Ashraf Ali M, Osman H, Ismail R, Choon TS, Yoon YK, et al.
    Bioorg Med Chem Lett, 2011 Jul 1;21(13):3997-4000.
    PMID: 21621414 DOI: 10.1016/j.bmcl.2011.05.003
    Hexacyclic derivatives share vital pharmacological properties, considered useful in Alzheimer's disease. The aim of this study was synthesis and its evaluation for acetyl cholinesterase inhibitory activity of novel hexacyclic analogues. Compound 4f, showed potent inhibitory activity against acetyl cholinesterase enzyme with IC(50) 0.72 μmol/L.
  12. Ali MA, Ismail R, Choon TS, Yoon YK, Wei AC, Pandian S, et al.
    Bioorg Med Chem Lett, 2010 Dec 1;20(23):7064-6.
    PMID: 20951037 DOI: 10.1016/j.bmcl.2010.09.108
    Series of pyrolidine analogues were synthesized and examined as acetylcholinesterase (AChE) inhibitors. Among the compounds, compounds 4k and 6k were the most potent inhibitors of the series. Compound 4k, showed potent inhibitory activity against acetyl cholinesterase enzyme with IC(50) 0.10 μmol/L. Pyrolidine analogues might be potential acetyl cholinesterase agents for AD.
  13. Wei AC, Ali MA, Yoon YK, Ismail R, Choon TS, Kumar RS, et al.
    Bioorg Med Chem Lett, 2012 Aug 1;22(15):4930-3.
    PMID: 22749825 DOI: 10.1016/j.bmcl.2012.06.047
    A series of twelve dispiropyrrolidines were synthesized using [3+2]-cycloaddition reactions. The synthesized compounds were screened for their antimycobacterial activity against M. tuberculosis H(37)Rv and INH resistant M. tuberculosis strains using agar dilution method, four of them showed good activity with MIC of less than 1 μM. Compound 4'-[5-(4-fluorophenyl)pyridin-3-yl]-1'-methyldispiro[indan-2,2' pyrrolidine-3',2″-indan]-1,3,1″-trione (4b) was found to be the most active with MIC of 0.1215 and 5.121 μM, respectively.
  14. Ashraf Ali M, Ismail R, Choon TS, Kumar RS, Osman H, Arumugam N, et al.
    Bioorg Med Chem Lett, 2012 Jan 1;22(1):508-11.
    PMID: 22142546 DOI: 10.1016/j.bmcl.2011.10.087
    Pyrrolothiazolyloxindole analogues share vital pharmacological properties, considered useful in Alzheimer's disease (AD). The aim of this study was synthesis and evaluate pyralothiazolyloxindole analogues if possess acetyl cholinesterase (AChE) inhibitory activity. The easily accessible one-pot synthesis of these compounds resulted to be significantly less difficult and expensive than that of donepezil. Several compounds possess anti-cholinesterase activity in the order of micro and sub-micromolar. Particularly, compound was the most potent inhibitors of the series against acetyl cholinesterase enzyme with IC(50) 0.11μmol/L.
  15. Pan Y, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, Pook PC, et al.
    Chem Biol Interact, 2011 Mar 15;190(1):1-8.
    PMID: 21276781 DOI: 10.1016/j.cbi.2011.01.022
    Orthosiphon stamineus (OS) has been traditionally used to treat diabetes, kidney and urinary disorders, high blood pressure and bone or muscular pain. To assess the possibility of drug-herb interaction via interference of metabolism, effects of four OS extracts of different polarity and three active constituents (sinensetin, eupatorin and rosmarinic acid) on major human cDNA-expressed cytochrome P450 (CYP) enzymes were investigated. Three substrate-probe based high-performance liquid chromatography (HPLC) assays were established to serve as activity markers for CYP2C9, CYP2D6 and CYP3A4. Our results indicate that OS extracts and constituents exhibited differential modulatory effects on different CYPs. While none of the OS components showed significant inhibition on CYP2C9, eupatorin strongly and uncompetitively inhibited CYP2D6 activity with a K(i) value of 10.2μM. CYP3A4 appeared to be the most susceptible enzyme to OS inhibitory effects. It was moderately inhibited by OS dichloromethane and petroleum ether extract with mixed-type and noncompetitive inhibitions (K(i)=93.7 and 44.9μg/mL), respectively. Correlation study indicated that the inhibition was accounted for by the presence of eupatorin in the extracts. When IC(50) values of these extracts were expressed in volume per dose unit to reflect inhibitory effect at recommended human doses from commercially available products, moderate inhibition was also observed. In addition, CYP3A4 was strongly and noncompetitively inhibited by eupatorin alone, with a K(i) value of 9.3μM. These findings suggest that co-administration of OS products, especially those with high eupatorin content, with conventional drugs may have the potential to cause drug-herb interactions involving inhibition of major CYP enzymes.
  16. Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.
    Pain Pract, 2017 09;17(7):930-940.
    PMID: 27996183 DOI: 10.1111/papr.12546
    BACKGROUND: Endogenous and exogenous opioids are substrates of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Genetic polymorphisms of ABCB1 may contribute to interindividual differences in pain modulation and analgesic responses. We investigated the relationship between ABCB1 polymorphisms and cold pain sensitivity among healthy males.

    METHODS: Cold pain responses, including pain threshold and pain tolerance, were measured using the cold-pressor test (CPT). DNA was extracted from whole blood and genotyped for ABCB1 polymorphisms, including c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642), using the allelic discrimination real-time polymerase chain reaction.

    RESULTS: A total of 152 participants were recruited in this observational study. Frequencies of mutated allele for c.1236C>T, c.2677G>T/A, and c.3435C>T polymorphisms were 56.6%, 49.7%, and 43.4%, respectively. Our results revealed an association of the CGC/CGC diplotype (c.1236C>T, c.2677G>T/A, and c.3435C>T) with cold pain sensitivity. Participants with the CGC/CGC diplotype had 90% and 72% higher cold pain thresholds (87.62 seconds vs. 46.19 seconds, P = 0.010) and cold pain tolerances (97.24 seconds vs. 56.54 seconds, P = 0.021), respectively, when compared with those without the diplotype.

    CONCLUSION: The CGC/CGC diplotype of ABCB1 polymorphisms was associated with variability in cold pain threshold and pain tolerance in healthy males.

  17. Kwan Z, Bong YB, Tan LL, Lim SX, Yong ASW, Ch'ng CC, et al.
    Arch. Dermatol. Res., 2018 Jul;310(5):443-451.
    PMID: 29687328 DOI: 10.1007/s00403-018-1832-x
    We investigated whether disease severity and clinical manifestations were associated with depression, anxiety, stress and quality of life in adults with psoriasis. Participants were recruited from a dermatology outpatient clinic at a teaching hospital. Information on sociodemographic characteristics, disease severity, presence of arthropathy and head involvement was specifically recorded. Disease severity was assessed using the Psoriasis Area and Severity Index (PASI). Quality of life and psychological symptoms were measured using the Dermatology Life Quality Index (DLQI) and the Depression Anxiety Stress Scale (DASS), respectively. One hundred individuals were recruited. Unadjusted analysis revealed that head involvement was associated with depression [odds ratio (OR) 8.509; 95% confidence interval (CI) 1.077-67.231] and anxiety (OR 6.46; 95% CI 1.401-29.858). Severe disease was associated with a poorer quality of life compared to mild disease (OR 3.750; 95% CI 1.330-10.577). Younger age was associated with an increased risk of depression [mean difference (MD) - 8.640; 95% CI - 16.390 to - 0.890], anxiety (MD - 11.553; 95% CI - 18.478 to- 4.628), stress (MD - 11.440; 95% CI - 19.252 to - 3.628) and severely impaired quality of life (MD - 12.338; 95% CI - 19.548 to - 5.127). Following adjustments for age and disease severity, anxiety, stress and depression remained associated with severely impaired quality of life.
    Study site: Dermatology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  18. Fadzil F, Shamsuddin K, Wan Puteh SE, Mohd Tamil A, Ahmad S, Abdul Hayi NS, et al.
    Obes Res Clin Pract, 2018 06 28;12(6):493-499.
    PMID: 29960869 DOI: 10.1016/j.orcp.2018.06.003
    BACKGROUND: Women of childbearing age are predisposed to becoming overweight or obese. This study determines the mean, prevalence and factors associated with 6 months postpartum weight retention among urban Malaysian mothers.

    METHODS: A prospective cohort study was conducted at baseline (after delivery), 2, 4 and 6 months postpartum. From 638 eligible mothers initially recruited, 420 completed until 6 months. Dependent variable was weight retention, defined as difference between weight at 6 months postpartum and pre-pregnancy weight, and weight retention ≥5kg was considered excessive. Independent variables included socio-demographic, history of pregnancy and delivery, lifestyle, practices and traditional postpartum practices.

    RESULTS: Average age was 29.61±4.71years, majority (83.3%) were Malays, 58.8% (low education), 70.0% (employed), 65.2% (middle income family), 33.8% (primiparous) and 66.7% (normal/instrumental delivery). Average gestational weight gain was 12.90±5.18kg. Mean postpartum weight retention was 3.12±4.76kg, 33.8% retaining ≥5kg. Bivariable analysis showed low income, primiparity, gestational weight gain ≥12kg, less active physically, higher energy, protein, carbohydrate and fat intake in diet, never using hot stone compression and not continuing breastfeeding were significantly associated with higher 6 months postpartum weight retention. From multivariable linear regression analysis, less active physically, higher energy intake in diet, gestational weight gain ≥12kg, not continuing breastfeeding 6 months postpartum and never using hot stone compression could explain 55.1% variation in 6 months postpartum weight retention.

    CONCLUSION: Women need to control gestational weight gain, remain physically active, reduce energy intake, breastfeed for at least 6 months and use hot stone compression to prevent high postpartum weight retention.

  19. Kwan Z, Bong YB, Tan LL, Lim SX, Yong AS, Ch'ng CC, et al.
    Psychol Health Med, 2017 02;22(2):184-195.
    PMID: 27541601 DOI: 10.1080/13548506.2016.1220603
    Patients with psoriasis may have increased risk of psychological comorbidities. This cross-sectional study aimed at determining associations between sociocultural and socioeconomic factors with the Depression Anxiety Stress Scale (DASS) scores and the Dermatology Life Quality Index (DLQI) scores. Adult patients with psoriasis were recruited from a Dermatology outpatient clinic via convenience sampling. Interviews were conducted regarding socio-demographic factors and willing subjects were requested to complete the DASS and DLQI questionnaires. The Pearson χ2 test, Fisher's exact test and multivariate logistic regression were used for statistical analysis to determine independent predictors of depression, anxiety, stress and severe impairment of quality of life. Unadjusted analysis revealed that depression was associated with Indian ethnicity (p = .041) and severe impairment of quality of life was associated with Indian ethnicity (p = .032), higher education (p = .013), higher income (p = .042), and employment status (p = .014). Multivariate analysis revealed that Indian ethnicity was a predictor of depression (p = .024). For stress, tertiary level of education (p = .020) was an independent risk factor while a higher monthly income was a protective factor (p = .042). The ethnic Indians and Malays were significantly more likely than the ethnic Chinese to suffer reduced quality of life (p = .001 and p = .006 respectively) and subjects with tertiary education were more likely to have severe impairment of quality of life (p = .002). Our study was unique in determining sociocultural influences on psychological complications of psoriasis in a South East Asian population. This has provided invaluable insight into factors predictive of adverse effects of psoriasis on psychological distress and quality of life in our patient population. Future studies should devise interventions to specifically target at risk groups in the development of strategies to reduce morbidity associated with psoriasis.
    Study site: Dermatology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  20. Yahaya R, Zahary MN, Othman Z, Ismail R, Nik Him NAS, Abd Aziz A, et al.
    Heliyon, 2020 May;6(5):e03948.
    PMID: 32426546 DOI: 10.1016/j.heliyon.2020.e03948
    Introduction: Schizophrenia is a chronic mental illness with clusters of symptoms, including cognitive impairment. This study aimed to explore the effect of Tualang Honey (TH) on cognitive domains, especially as it pertained to the verbal memory of schizophrenia patients.

    Method: This was a cross-sectional study involved 80 individuals, diagnosed with schizophrenia. The Malay Version Auditory Verbal Learning Test (MVAVLT) was used. Data were analysed using SPSS 20.0 software. Intention to treat analysis was applied.

    Result: A comparison of the total learning score at eight weeks between the two groups based on time effect and time-treatment interaction favoured TH group.

    Conclusion: This study concludes that by supplementing schizophrenia patients with 8-week of TH did improve total learning performance across domains in the immediate memory among patients with schizophrenia.

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