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A facile three-component [3+2]-cycloaddition for the regioselective synthesis of highly functionalised dispiropyrrolidines acting as antimycobacterial agents

Wei AC, Ali MA, Yoon YK, Ismail R, Choon TS, Kumar RS

Bioorg Med Chem Lett, 2013 Mar 1;23(5):1383-6.
PMID: 23352268 DOI: 10.1016/j.bmcl.2012.12.069

A series of fourteen dispiropyrrolidines were synthesized using [3+2]-cycloaddition reactions and were screened for their antimycobacterial activity against Mycobacterium tuberculosis H(37)Rv in HTS (High Throughput Screen). Most of the compounds showed moderate to good activity with MIC of less than 20 μM. Compound 4'-(4-bromophenyl)-1'-methyldispiro[acenaphthylene-1,2'-pyrrolidine-3',2″-indane]-2,1″(1H)-dione (4c) was found to be the most active with MIC of 12.50 μM.
Functional role of Ile264 in CYP2C8: mutations affect haem incorporation and catalytic activity

Singh R, Ting JG, Pan Y, Teh LK, Ismail R, Ong CE

Drug Metab. Pharmacokinet., 2008;23(3):165-74.
PMID: 18574320

The work described in this study aimed to express CYP2C8 wild-type and mutant proteins in bacterial expression system and to use the expressed proteins to investigate the structural and functional consequences of a reported allele CYP2C8(*)4 (carrying Ile264Met substitution) on protein activity. Ile264 was replaced by three different amino acids resulting in three mutant constructs, 2C8I264M, 2C8I264R and 2C8I264D. The presence of isoleucine at position 264 in CYP2C8 was found to be important for proper haem insertion and protein folding; whereas bulkier or charged residues were highly disruptive resulting in inactive proteins with minimum spectral and catalytic activities. This was evidenced from the low levels of Soret peak at 450 nm and negligible levels of tolbutamide methylhydroxylase activity. Kinetic study using paclitaxel indicated that all three mutants exhibited only 9.7 to 35.4% of the activity level observed in the wild-type. In addition, the mutants were more sensitive to proteinase K digestion, indicating a possible alteration of conformation. The combined effects of protein instability and compromised catalytic activity resulted in defective CYP2C8 protein which may have clinical implications in carriers of CYP2C8*4, particularly in terms of their capacity to clear potent drugs and their susceptibility to adverse drug reactions.
Fulltext Expression of survivin and its clinicopathological correlations in invasive ductal carcinoma of the breast

Al-Joudi FS, Iskandar ZA, Hasnan J, Rusli J, Kamal Y, Imran AK, et al.

Singapore Med J, 2007 Jul;48(7):607-14.
PMID: 17609820

INTRODUCTION: Survivin is a 16.5-kDa intracellular protein that inhibits apoptosis and regulates cell division, and belongs to the inhibitors of apoptosis gene family. It appears to have an important role in regulating apoptosis at the cell cycle checkpoints. Survivin has been found to have a differential distribution in cancer compared to normal tissue, as it is over-expressed in malignant tumours.
METHODS: In addition to the demographical analysis of the disease, data from 382 women with invasive ductal carcinoma of the breast were collected from three hospitals in Northeast Malaysia, and analysed for survivin expression by immunohistochemistry.
RESULTS: Invasive ductal carcinoma of the breast was found to be the most prevalent breast cancer type. Survivin was detected in 260 (68.1 percent) study cases. In addition, significant correlations have been shown between survivin expression on one hand, and tumour size and lymph node involvement on the other hand (p-value is less than 0.05). However, no significant correlations were found with other clinicopathological factors, such as tumour histological grade, tumour side, oestrogen and progesterone receptors. Nuclear expression of survivin was detected in 16.5 percent of the study cases, cytoplasmic expression was detected in 24.1 percent, and 27.5 percent of the cases expressed survivin in both nuclear and cytoplasmic locations simultaneously. The subcellular localisation of survivin was significantly correlated (p is less than 0.001) with the lymph node involvement indicating its value in predicting the aggressiveness of tumour cells, since it increases the resistance to apoptosis and promotes cell proliferation.
CONCLUSION: This is the fi rst known report on survivin expression in cancer in West Malaysia and Southeast Asia. It emphasises the importance of the detection of survivin in breast cancer to aid in diagnosis, confirm malignancy, and to assess the disease progress and response to therapy.
Nerve conduction study of healthy Asian Malays: the influence of age on median, ulnar, and sural nerves

Awang MS, Abdullah JM, Abdullah MR, Tahir A, Tharakan J, Prasad A, et al.

Med Sci Monit, 2007 Jul;13(7):CR330-2.
PMID: 17599028

Nerve conduction study is essential in the diagnosis of focal neuropathies and diffuse polyneuropathies. There are many factors that can affect nerve conduction velocity, and age is one of them. Most of the many studies of this effect, and the values from them, were on Caucasian subjects. Therefore, this study was designed to investigate the effect of age on conduction velocity among healthy Asian Malay subjects by analyzing its influence on the median, ulnar, and sural nerves.
Prevalence and associated factors of head lice infestation among primary schoolchildren in Kelantan, Malaysia

Bachok N, Nordin RB, Awang CW, Ibrahim NA, Naing L

Southeast Asian J Trop Med Public Health, 2006 May;37(3):536-43.
PMID: 17120976

Head lice infestation contributes a significant morbidity among schoolchildren in Malaysia. A cross-sectional study was designed to determine the prevalence and associated factors of head lice infestation among primary schoolchildren in Kelantan, Malaysia. Six schools were randomly selected from three sub-districts of Kuala Krai, Kelantan. A total of 463 eleven-year-old pupils were screened by visual scalp examination and fine-toothed combing. Self-administered questionnaire was used to collect data on socio-demography and associated factors of head lice infestation. The prevalence of head lice infestation was 35.0% (95% Cl: 30.6, 39.3) with 11.9% inactive, 23.1% active, 18.2% light and 16.8% heavy infestations. The associated factors were girls; family income of RM247 or less; head lice infestation of family member and having four or more siblings. The high prevalence of head lice infestation in this study indicates the need for regular school health program that emphasis on the eradication of head lice. The significant associated factors identified in this study reconfirm the importance of controlling the transmissibility of head lice. Pupils and parents should be informed regarding factors that may facilitate the transmission of head lice.
Fulltext Analysis of simple sequence repeat markers linked with blast disease resistance genes in a segregating population of rice (Oryza sativa)

Ashkani S, Rafii MY, Sariah M, Siti Nor Akmar A, Rusli I, Abdul Rahim H, et al.

Genet. Mol. Res., 2011 Jul 06;10(3):1345-55.
PMID: 21751161 DOI: 10.4238/vol10-3gmr1331

Among 120 simple sequence repeat (SSR) markers, 23 polymorphic markers were used to identify the segregation ratio in 320 individuals of an F(2) rice population derived from Pongsu Seribu 2, a resistant variety, and Mahsuri, a susceptible rice cultivar. For phenotypic study, the most virulent blast (Magnaporthe oryzae) pathotype, P7.2, was used in screening of F(2) population in order to understand the inheritance of blast resistance as well as linkage with SSR markers. Only 11 markers showed a good fit to the expected segregation ratio (1:2:1) for the single gene model (d.f. = 1.0, P < 0.05) in chi-square (χ(2)) analyses. In the phenotypic data analysis, the F(2) population segregated in a 3:1 (R:S) ratio for resistant and susceptible plants, respectively. Therefore, resistance to blast pathotype P7.2 in Pongsu Seribu 2 is most likely controlled by a single nuclear gene. The plants from F(2) lines that showed resistance to blast pathotype P7.2 were linked to six alleles of SSR markers, RM168 (116 bp), RM8225 (221 bp), RM1233 (175 bp), RM6836 (240 bp), RM5961 (129 bp), and RM413 (79 bp). These diagnostic markers could be used in marker assisted selection programs to develop a durable blast resistant variety.
Antimycobacterial activity: synthesis of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues

Ali MA, Ismail R, Choon TS, Pandian S, Hassan Ansari MZ

J Enzyme Inhib Med Chem, 2011 Aug;26(4):598-602.
PMID: 21714764 DOI: 10.3109/14756366.2010.529805

In this study, a series of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues were synthesized and evaluated for antimycobacterial activity against Mycobacterium tuberculosis (MTB) H(37)Rv and isoniazid resistant M. tuberculosis (INHR-MTB). All the newly synthesized compounds were showing moderate to high inhibitory activities. The compound 6,7-dimethoxy-3-(4-chloro phenyl)-4H-indeno[1,2-c]isoxazole (4b) was found to be the most promising compound, active against MTB H(37)Rv and INHR-MTB with minimum inhibitory concentrations of 0.22 and 0.34 μM.
Fulltext Effects of acute gamma irradiation on physiological traits and flavonoid accumulation of Centella asiatica

Moghaddam SS, Jaafar H, Ibrahim R, Rahmat A, Aziz MA, Philip E

Molecules, 2011 Jun 17;16(6):4994-5007.
PMID: 21694666 DOI: 10.3390/molecules16064994

In the present study, two accessions of Centella asiatica (CA03 and CA23) were subjected to gamma radiation to examine the response of these accessions in terms of survival rate, flavonoid contents, leaf gas exchange and leaf mass. Radiation Sensitivity Tests revealed that based on the survival rate, the LD(50) (gamma doses that killed 50% of the plantlets) of the plantlets were achieved at 60 Gy for CA03 and 40 Gy for CA23. The nodal segments were irradiated with gamma rays at does of 30 and 40 Gy for Centella asiatica accession 'CA03' and 20 and 30 Gy for accession 'CA23. The nodal segment response to the radiation was evaluated by recording the flavonoid content, leaf gas exchange and leaf biomass. The experiment was designed as RCBD with five replications. Results demonstrated that the irradiated plantlets exhibited greater total flavonoid contents (in eight weeks) significantly than the control where the control also exhibited the highest total flavonoid contents in the sixth week of growth; 2.64 ± 0.02 mg/g DW in CA03 and 8.94 ± 0.04 mg/g DW in CA23. The total flavonoid content was found to be highest after eight weeks of growth, and this, accordingly, stands as the best time for leaf harvest. Biochemical differentiation based on total flavonoid content revealed that irradiated plantlets in CA23 at 20 and 30 Gy after eight weeks contained the highest total flavonoid concentrations (16.827 ± 0.02; 16.837 ± 0.008 mg/g DW, respectively) whereas in CA03 exposed to 30 and 40 Gy was found to have the lowest total flavonid content (5.83 ± 0.11; 5.75 ± 0.03 mg/g DW). Based on the results gathered in this study, significant differences were found between irradiated accessions and control ones in relation to the leaf gas. The highest PN and gs were detected in CA23 as control followed by CA23 irradiated to 20Gy (CA23G20) and CA23G30 and the lowest PN and gs were observed in CA03 irradiated to 40Gy (CA03G40). Moreover, there were no significant differences in terms of PN and gs among the irradiated plants in each accession. The WUE of both irradiated accessions of Centella asiatica were reduced as compared with the control plants (p < 0.01) while Ci and E were enhanced. There were no significant differences in the gas exchange parameters among radiated plants in each accession. Moreover, malondialdehyde (MDA) of accessions after gamma treatments were significantly higher than the control, however, flavonoids which were higher concentration in irradiated plants can scavenge surplus free radicals. Therefore, the findings of this study have proven an efficient method of in vitro mutagenesis through gamma radiation based on the pharmaceutical demand to create economically superior mutants of C. asiatica. In other words, the results of this study suggest that gamma irradiation on C. asiatica can produce mutants of agricultural and economical importance.
Optimization of an efficient semi-solid culture protocol for sterilization and plant regeneration of Centella asiatica (L.) as a medicinal herb

Moghaddam SS, Jaafar HB, Aziz MA, Ibrahim R, Rahmat AB, Philip E

Molecules, 2011;16(11):8981-91.
PMID: 22439138

The present study investigates the effects of different concentrations, as well as type of plant growth regulators (PGRs) and medium (MS, Duchefa) on the growth and development of Centella asiatica in semi-solid culture. In addition, a protocol for successful sterilization of C.asiatica explants prepared from field-grown plants highly exposed to fungal and bacterial contamination was determined. Results for sterilization treatments revealed that applying HgCl₂ and Plant Preservative Mixture (PPM) with cetrimide, bavistin and trimethoprim which were included after washing with tap water, followed by the addition of PPM in the medium, produced a very satisfactory result (clean culture 90 ± 1.33%) and TS5 (decon + cetrimide 1% + bavistin 150 mg/L + trimethoprim 50 mg/L + HgCl₂0.1% + PPM 2% soak and 2 mL/L in medium) was hence chosen as the best method of sterilization for C.asiatica. The synergistic combination of 6 benzylaminopurine (BAP) and 1-naphthaleneacetic acid (NAA) in concentrations of 2 mg/L and 0.1 mg/L, respectively, in Duchefa medium compared with MS induced the most optimal percentage of sprouted shoots (93 ± 0.667), number of shoots (5.2 ± 0.079) and nodes (4 ± 0.067) per explant, leaf per explant (14 ± 0.107) and shoot length (4.1 ± 0.67 cm). Furthermore, optimum rooting frequency (95.2 ± 0.81%), the number of roots/shoot (7.5 ± 0.107) and the mean root length (4.5 ± 0.133 cm) occurred for shoots that were cultured on full-strength MS medium containing 0.5 mg/L indole-3-butyric acid (IBA). In this study, the acclimatized plantlets were successfully established with almost 85% survival. The findings of this study have proven an efficient medium and PGR concentration for the mass propagation of C.asiatica. These findings would be useful in micropropagation and ex situ conservation of this plant.
What is the meaning of palliative care in the Asia-Pacific region?

O'Connor M, O'Brien AP, Griffiths D, Poon E, Chin J, Payne S, et al.

Asia Pac J Clin Oncol, 2010 Sep;6(3):197-202.
PMID: 20887501 DOI: 10.1111/j.1743-7563.2010.01315.x

This paper describes the preliminary work required to understand cultural differences in palliative care in the United Kingdom and three countries in the Asia-Pacific region, in preparation for a cross-country study. The study is intended to address cultural understandings of palliative care, the role of the family in end of life care, what constitutes good care and the ethical issues in each country. Suggestions are then made to shape the scope of the study and to be considered as outcomes to improve care of the dying in these countries. It is anticipated that the method used to achieve consensus on cross-country palliative care issues will be both qualitative and quantitative. Identifying key priorities in the delivery and quality measures of palliative care will involve participants in focus groups, a Delphi survey and in the development of clinical indicators towards creating standards of palliative care common to the Asian Pacific region.
Fulltext Prevalence and factors associated with stress among secondary school teachers in Kota Bharu, Kelantan, Malaysia

Abdul Hadi A, Naing NN, Daud A, Nordin R, Sulong MR

Southeast Asian J Trop Med Public Health, 2009 Nov;40(6):1359-70.
PMID: 20578472

The teaching profession is an occupation at high risk for stress. This research attempted to determine the prevalence of stress and the associated factors contributing to stress among teachers in Malaysia. A cross-sectional study was conducted on 580 secondary school teachers in Kota Bharu District. The instrument used to carry out the study was adopted and modified from the Depression, Anxiety and Stress Scale (DASS 21) and Job Content Questionnaire (JCQ). The questionnaire consisted of two parts: Part I consisting non-job factors (socio-demographic characteristics) and Part II consisting of psychosocial factors contributing to stress. Simple and multiple linear regression analysis were carried out. The prevalence of stress was reported as 34.0%. Seventeen point four percent of teachers experienced mild stress. Age, duration of work and psychological job demands were significantly associated with stress level. This study indicates job-related factors did not contribute much to stress among secondary school teachers. Non-job-related factors should be further studied to determine methods for stress reduction in teachers in Malaysia.
Functional characterization of cytochrome P450 2A6 allelic variants CYP2A6*15, CYP2A6*16, CYP2A6*21, and CYP2A6*22

Tiong KH, Yiap BC, Tan EL, Ismail R, Ong CE

Drug Metab Dispos, 2010 May;38(5):745-51.
PMID: 20139165 DOI: 10.1124/dmd.109.031054

Variation in CYP2A6 levels and activity can be attributed to genetic polymorphism and, thus, functional characterization of allelic variants is necessary to define the importance of CYP2A6 polymorphism in humans. The aim of the present study was to investigate the reported alleles CYP2A6*15, CYP2A6*16, CYP2A6*21, and CYP2A6*22, in terms of the functional consequences of their mutations on the enzyme catalytic activity. With use of the wild-type CYP2A6 cDNA as template, site-directed mutagenesis was performed to introduce nucleotide changes encoding K194E substitution in CYP2A6*15, R203S substitution in CYP2A6*16, K476R substitution in CYP2A6*21, and concurrent D158E and L160I substitutions in CYP2A6*22. Upon sequence verification, the CYP2A6 wild-type and mutant constructs were individually coexpressed with NADPH-cytochrome P450 reductase in Escherichia coli. A kinetic study using a coumarin 7-hydroxylase assay indicated that CYP2A6*15 exhibited higher V(max) than the wild type, whereas all mutant constructs, except for variant CYP2A6*16, exhibited higher K(m) values. Analysis of the V(max)/K(m) ratio revealed that all mutants demonstrated 0.85- to 1.05-fold differences from the wild type, with the exception of variant CYP2A6*22, which only portrayed 39% of the wild-type intrinsic clearance. These data suggested that individuals carrying the CYP2A6*22 allele are likely to have lower metabolism of CYP2A6 substrate than individuals expressing CYP2A6*15, CYP2A6*16, CYP2A6*21, and the wild type.
In vitro effect of important herbal active constituents on human cytochrome P450 1A2 (CYP1A2) activity

Pan Y, Tiong KH, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, et al.

Phytomedicine, 2014 Oct 15;21(12):1645-50.
PMID: 25442272 DOI: 10.1016/j.phymed.2014.08.003

This study was designed to investigate eight herbal active constituents (andrographolide, asiaticoside, asiatic acid, madecassic acid, eupatorin, sinensetin, caffeic acid, and rosmarinic acid) on their potential inhibitory effects on human cytochrome P450 1A2 (CYP1A2) activity. A fluorescence-based enzyme assay was performed by co-incubating human cDNA-expressed CYP1A2 with its selective probe substrate, 3-cyano-7-ethoxycoumarin (CEC), in the absence or presence of various concentrations of herbal active constituents. The metabolite (cyano-hydroxycoumarin) formed was subsequently measured in order to obtain IC50 values. The results indicated that only eupatorin and sinensetin moderately inhibited CYP1A2 with IC50 values of 50.8 and 40.2 μM, while the other active compounds did not significantly affect CYP1A2 activity with IC50 values more than 100 μM. Ki values further determined for eupatorin and sinensetin were 46.4 and 35.2 μM, respectively. Our data indicated that most of the investigated herbal constituents have negligible CYP1A2 inhibitory effect. In vivo studies however may be warranted to ascertain the inhibitory effect of eupatorin and sinensetin on CYP1A2 activity in clinical situations.
Fulltext Relationship between cold pressor pain-sensitivity and sleep quality in opioid-dependent males on methadone treatment

Zahari Z, Lee CS, Tan SC, Mohamad N, Lee YY, Ismail R

PeerJ, 2015;3:e839.
PMID: 25870765 DOI: 10.7717/peerj.839

Aim. Poor sleep quality due to pain has been reported among opioid-dependent male patients on methadone maintenance therapy (MMT) but objective pain data are lacking. This study aimed to investigate the rate of pain-sensitivity using cold pressor test (CPT) and the relationship between pain-sensitivity and sleep quality in this population.
Methods. A total of 168 male participants were included into the study. Objective pain-tolerance was evaluated at 0 h and at 24 h after the first CPT. Malay version of the Pittsburgh Sleep Quality Index (PSQI) and the subjective opiate withdrawal scale (SOWS) questionnaires were administered to evaluate the quality of sleep and withdrawal symptoms, respectively.
Results. The mean age of study participants was 37.22 (SD 6.20) years old. Mean daily methadone dose was 76.64 (SD 37.63) mg/day, mean global PSQI score was 5.47 (SD 2.74) and mean averaged SOWS score was 5.43 (SD 6.91). The averaged pain-tolerance time ranged from 7 to 300 s with a mean time of 32.16 (SE 2.72) s, slightly below the cut-off score of 37.53 s. More specifically, 78.6% (n = 132) of participants were identified as pain-sensitive (averaged pain-tolerance time ≤37.53 s), and 36 (21.4%) participants were pain-tolerant (averaged pain-tolerance time >37.53 s). The pain-sensitive group reported poorer sleep quality with mean (SD) PSQI of 5.78 (2.80) compared with the pain-tolerant group with mean (SD) PSQI of 4.31 (2.18) (p = 0.005). With analysis of covariance, pain-sensitive group was found to have higher global PSQI scores (adjusted mean 5.76, 95% CI 5.29; 6.22) than pain-tolerant participants (adjusted mean 4.42, 95% CI 3.52; 5.32) (p = 0.010).
Conclusions. Majority of opioid-dependent male patients on methadone treatment are pain-sensitive with CPT. Poor sleep quality is associated with cold pressor pain-sensitivity. Pain and sleep complaints in this male population should not be overlooked.
Study site: Hospital Universiti Sains Malaysia (HUSM) and other MMT clinics (Kota Bharu, Pasir Mas, Pasir Puteh and Bachok), Kelantan, Malaysia
Fulltext Inhibitory potency of 8-methoxypsoralen on cytochrome P450 2A6 (CYP2A6) allelic variants CYP2A6 15, CYP2A6 16, CYP2A6 21 and CYP2A6 22: differential susceptibility due to different sequence locations of the mutations

Tiong KH, Mohammed Yunus NA, Yiap BC, Tan EL, Ismail R, Ong CE

PLoS One, 2014;9(1):e86230.
PMID: 24475091 DOI: 10.1371/journal.pone.0086230

Human cytochrome P450 2A6 (CYP2A6) is a highly polymorphic isoform of CYP2A subfamily. Our previous kinetic study on four CYP2A6 allelic variants (CYP2A6 15, CYP2A6 16, CYP2A6 21 and CYP2A6 22) have unveiled the functional significance of sequence mutations in these variants on coumarin 7-hydroxylation activity. In the present study, we further explored the ability of a typical CYP2A6 inhibitor, 8-methoxypsoralen (8-MOP), in inhibition of these alleles and we hypothesized that translational mutations in these variants are likely to give impact on 8-MOP inhibitory potency. The CYP2A6 variant and the wild type proteins were subjected to 8-MOP inhibition to yield IC50 values. In general, a similar trend of change in the IC50 and Km values was noted among the four mutants towards coumarin oxidation. With the exception of CYP2A6 16, differences in IC50 values were highly significant which implied compromised interaction of the mutants with 8-MOP. Molecular models of CYP2A6 were subsequently constructed and ligand-docking experiments were performed to rationalize experimental data. Our docking study has shown that mutations have induced enlargement of the active site volume in all mutants with the exception of CYP2A6 16. Furthermore, loss of hydrogen bond between 8-MOP and active site residue Asn297 was evidenced in all mutants. Our data indicate that the structural changes elicited by the sequence mutations could affect 8-MOP binding to yield differential enzymatic activities in the mutant CYP2A6 proteins.
Fulltext Relationship between Psychosocial Risk Factors and Work-Related Musculoskeletal Disorders among Public Hospital Nurses in Malaysia

Amin NA, Nordin R, Fatt QK, Noah RM, Oxley J

Ann Occup Environ Med, 2014;26:23.
PMID: 25852937 DOI: 10.1186/s40557-014-0023-2

OBJECTIVE: This study examined the relationships between psychosocial work factors and risk of WRMSDs among public hospital nurses in the Klang Valley, Malaysia.
METHODS: We conducted a cross-sectional study among 660 public hospital nurses. A self-administered questionnaire was used to collect data on the occurrence of WRMSDs according to body regions, socio-demographic profiles, occupational information and psychosocial risk factors. 468 questionnaires were returned (response rate of 71%), and 376 questionnaires qualified for subsequent analysis. Univariate analyses were applied to test for mean and categorical differences across the WRMSDs; multiple logistic regression was applied to predict WRMSDs based on the Job Strain Model's psychosocial risk factors.
RESULTS: Over two thirds of the sample of nurses experienced discomfort or pain in at least one site of the musculoskeletal system within the last year. The neck was the most prevalent site (48.94%), followed by the feet (47.20%), the upper back (40.69%) and the lower back (35.28%). More than 50% of the nurses complained of having discomfort in region one (neck, shoulders and upperback) and region four (hips, knees, ankles, and feet). The results also revealed that psychological job demands, job strain and iso-strain ratio demonstrated statistically significant mean differences (p
Synthesis, structure and theoretical investigation into a homoleptic tris(dithiolene) tungsten

Arifin K, Minggu LJ, Daud WR, Yamin BM, Daik R, Kassim MB

Spectrochim Acta A Mol Biomol Spectrosc, 2014;120:208-15.
PMID: 24184623 DOI: 10.1016/j.saa.2013.09.069

A new homoleptic dithiolene tungsten complex, tris-{1,2-bis(3,5-dimethoxyphenyl)-1,2-ethylenodithiolene-S,S'}tungsten, was successfully synthesized via a reaction of the thiophosphate ester and sodium tungstate. The thiophosphate ester was prepared from 3,5-dimethoxybenzaldehyde via benzoin condensation to produce the intermediate 1,2-bis-(3,5-dimethoxyphenyl)-2-hydroxy-ethanone compound, followed by a reaction of the intermediate with phosphorus pentasulfide. FTIR, UV-Vis spectroscopy, 1H NMR and 13C NMR and elemental analysis confirmed the product as tris{1,2-bis-(3,5-dimethoxyphenyl)-1,2-ethylenodithiolene-S,S'}tungsten with the molecular formula of C54H54O12S6W. Crystals of the product adopted a monoclinic system with space group of P2(1)/n, where a=12.756(2) Å, b=21.560(3) Å, c=24.980(4) Å and β=103.998(3)°. Three thioester ligands were attached to the tungsten as bidentate chelates to form a distorted octahedral geometry. Density functional theory calculations were performed to investigate the molecular properties in a generalized-gradient approximation framework system using Perdew-Burke-Ernzerhof functions and a double numeric plus polarization basis set. The HOMO was concentrated on the phenyl ligands, while the LUMO was found along the W(S2C2)3 rings. The theoretical optical properties showed a slight blue shift in several low dielectric solvents. The solvatochromism effect was insignificant for high polar solvents.
Effect of eurycomanone on cytochrome P450 isoforms CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 in vitro

Pan Y, Tiong KH, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, et al.

J Nat Med, 2014 Apr;68(2):402-6.
PMID: 23881640 DOI: 10.1007/s11418-013-0794-8

Eurycomanone, an active constituent isolated from Eurycoma longifolia Jack, was examined for modulatory effects on cytochrome P450 (CYP) isoforms CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 using in vitro assays. The IC50 value was determined to assess the potencies of modulation for each CYP isoform. Our results indicated that eurycomanone did not potently inhibit any of the CYP isoforms investigated, with IC50 values greater than 250 μg/ml. Hence there appears to be little likelihood of drug-herb interaction between eurycomanone or herbal products with high content of this compound and CYP drug substrates via CYP inhibition.
Report: Demographic profiles and sleep quality among patients on methadone maintenance therapy (MMT) in Malaysia

Zahari Z, Siong LC, Musa N, Mohd Yasin MA, Choon TS, Mohamad N, et al.

Pak J Pharm Sci, 2016 Jan;29(1):239-46.
PMID: 26826835

Poor sleep quality was frequently reported by opioid dependence patients during methadone maintenance therapy (MMT). The study investigated a sample of patients on MMT to investigate the severity and prevalence of sleep problems in MMT patients. We evaluated sleep quality and disturbances of 119 Malay male patients from MMT clinics in Kelantan, Malaysia between March and July 2013 using the Pittsburgh Sleep Quality Index (PSQI)-Malay version. Patients' demographic, clinical data, past drug history and methadone treatment variables were recorded. Patients averaged 37.5 years of age (SD 6.79) and their mean age of first time illicit drug use was 19.3 years (SD 4.48). Their mean age of entering MMT was 34.7 years (SD 6.92) and the mean duration in MMT was 2.8 years (SD 2.13). The mean current daily dosage of methadone was 77.8 mg (SD 39.47) and ranged from 20 to 360 mg. The mean global PSQI score was 5.6 (SD 2.79) and 43.7% patients were identified as 'poor sleepers' (global PSQI scores >5). This study confirms the poor overall sleep quality among patients on MMT. The prevalence and severity of sleep problems in MMT patients should not be underestimated.
High allele frequency of CYP2C9*3 (rs1057910) in a Negrito's subtribe population in Malaysia; Aboriginal people of Jahai

Rosdi RA, Mohd Yusoff N, Ismail R, Soo Choon T, Saleem M, Musa N, et al.

Ann Hum Biol, 2015 Sep 24.
PMID: 26402341

CYP2C9 gene polymorphisms modulate inter-individual variations in the human body's responses to various endogenous and exogenous drug substrates. To date, little is known about the CYP2C9 gene polymorphisms among the aboriginal populations of the world, including those in Malaysia.

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