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Fulltext Ethyl 2-[4-(morpholin-4-yl)phen-yl]-1-[3-(2-oxopyrrolidin-1-yl)prop-yl]-1H-1,3-benzimidazole-5-carboxyl-ate monohydrate

Yoon YK, Ali MA, Choon TS, Arshad S, Razak IA

Acta Crystallogr Sect E Struct Rep Online, 2012 Oct 1;68(Pt 10):o2967-8.
PMID: 23125749 DOI: 10.1107/S1600536812039268

The asymmetric unit of the title compound, C(27)H(32)N(4)O(4)·H(2)O, contains two independent benzimidazole-5-carboxyl-ate mol-ecules and two water mol-ecules. In both main mol-ecules, the pyrrolidine rings are in an envelope conformation with a methyl-ene C atom as the flap. The morpholine rings adopt chair conformations. Both benzimidazole rings are essentially planar, with maximum deviations of 0.008 (1) Å, and form dihedral angles of 37.65 (6) and 45.44 (6)° with the benzene rings. In one mol-ecule, an intra-molecular C-H⋯O hydrogen bond forms an S(7) ring motif. In the crystal, O-H⋯O and O-H⋯N hydrogen bonds connect pairs of main mol-ecules and pairs of water mol-ecules into two independent centrosymmetric four-compoment aggregates. These aggregates are connect by C-H⋯O hydrogen bonds leading to the formation of a three-dimensional network, which is stabilized by C-H⋯π interactions.
Fulltext 4'-(3-Bromo-phen-yl)-1'-methyl-dispiro-[indan-2,2'-pyrrolidine-3',2''-indan]-1,3,1''-trione

Wei AC, Ali MA, Choon TS, Arshad S, Razak IA

Acta Crystallogr Sect E Struct Rep Online, 2012 Oct 1;68(Pt 10):o2907-8.
PMID: 23125700 DOI: 10.1107/S1600536812037993

In the title compound, C(27)H(20)BrNO(3), two intra-molecular C-H⋯O hydrogen bonds both form S(6) rings. The pyrrolidine ring adopts a twisted conformation about the C-C bond bearing the indane ring systems. The other two five-membered rings within the indane systems are in shallow envelope conformations, with the spiro C atoms as the flap atoms. The mean plane of the pyrrolidine ring [maximum deviation = 0.275 (1) Å] makes dihedral angles of 65.25 (7), 78.33 (6) and 75.25 (6)° with the bromo-substituted benzene ring and the mean planes of the mono- and dioxo-substituted indane rings, respectively. In the crystal, mol-ecules are linked by C-H⋯O and C-H⋯N hydrogen bonds into a three-dimensional network. In addition, C-H⋯π inter-actions are observed.
Insecticide susceptibility status of field-collected Aedes (Stegomyia) aegypti (L.) at a dengue endemic site in Shah Alam, Selangor, Malaysia

Rong LS, Ann AT, Ahmad NW, Lim LH, Azirun MS

Southeast Asian J Trop Med Public Health, 2012 Jan;43(1):34-47.
PMID: 23082552

Biweekly ovitrap surveillance (OS) was conducted for a year (August 2007 - September 2008) at two different dengue endemic sites in Shah Alam, Selangor, Malaysia, 50 km from Kuala Lumpur. Aedes aegypti collected from these 2 locations were raised to the F3 stage and subjected to a WHO standard bioassay method to determine lethal time (LT) against pyrethroids (permethrin 0.75%, cyfluthrin 0.15%), organophosphates (malathion 5.0%, fenitrothion 1.0%), carbamates (propoxur 0.1%, bendiocarb 0.1%) and organochlorine (DDT 4.0%). Insecticide susceptibilities were analyzed for one year. Aedes aegypti were resistant to DDT with a mortality range of 0 - 13.3% throughout the year at both sites. Susceptibilities to pyrethroids and carbamates varied throughout the year. In contrast, susceptibilities to pyrethroids and carbamates varied throughout the year: resistant to propoxur, bendiocarb and permethrin with mortality of < 80% in most months; but, showed incipient resistant to cyfluthrin in most months. Mosquitoes were consistently susceptible to malathion and fenitrothion, with complete mortality during most months. They were especially susceptible to malathion with LT50 values of 21.32 - 36.37 minutes, suggesting effectiveness of malathion for control of dengue.
The effect of mitragynine on cAMP formation and mRNA expression of mu-opioid receptors mediated by chronic morphine treatment in SK-N-SH neuroblastoma cell

Jamil MF, Subki MF, Lan TM, Majid MI, Adenan MI

J Ethnopharmacol, 2013 Jun 21;148(1):135-43.
PMID: 23608241 DOI: 10.1016/j.jep.2013.03.078

ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] Mitragynine is an indole alkaloid compound of Mitragyna speciosa (M. speciosa) Korth. (Rubiaceae). This plant is native to the southern regions of Thailand and northern regions of Malaysia and is frequently used to manage the withdrawal symptoms in both countries.
AIM OF STUDY: To investigate the effect of mitragynine after chronic morphine treatment on cyclic AMP (cAMP) level and mRNA expression of mu-opioid receptor (MOR) in human neuroblastoma SK-N-SH cell.
METHOD AND MATERIALS: Mitragynine was isolated from the Mitragyna speciosa plant using the acid-base extraction method. The cAMP level upon forskolin stimulation in the cells was determined using the Calbiochem(®) Direct Immunoassay Kit. The mRNA expression of the MOR was carried out using quantitative RT-PCR.
RESULT: Cotreatment and pretreatment of morphine and mitragynine significantly reduced the production of cAMP level at a lower concentration of mitragynine while the higher concentration of this compound could lead to the development of tolerance and dependence as shown by the increase of the cAMP level production in foskolin stimulation. In MOR mRNA expression study, cotreatment of morphine with mitragynine significantly reduced the down-regulation of MOR mRNA expression as compared to morphine treatment only.
CONCLUSION: These finding suggest that mitragynine could possibly avoid the tolerance and dependence on chronic morphine treatment by reducing the up-regulation of cAMP level as well as reducing the down-regulation of MOR at a lower concentration of mitragynine.
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.
Docking of noncompetitive inhibitors into dengue virus type 2 protease: understanding the interactions with allosteric binding sites

Othman R, Kiat TS, Khalid N, Yusof R, Newhouse EI, Newhouse JS, et al.

J Chem Inf Model, 2008 Aug;48(8):1582-91.
PMID: 18656912 DOI: 10.1021/ci700388k

A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously reported to show varying degrees of noncompetitive inhibitory activities toward Dengue virus type 2 (Den2) protease. Results obtained from automated docking studies are in agreement with experimental data in which the ligands were shown to bind to sites other than the active site of the protease. The calculated K(i) values are very small, indicating that the ligands bind quite well to the allosteric binding site. Greater inhibition by pinostrobin, compared to the other compounds, can be explained by H-bonding interaction with the backbone carbonyl of Lys74, which is bonded to Asp75 (one of the catalytic triad residues). In addition, structure-activity relationship analysis yields structural information that may be useful for designing more effective therapeutic drugs against dengue virus infections.
Immunohistochemical determination of the P15 protein expression in cutaneous squamous cell carcinoma

Moad AI, Lan TM, Kaur G, Hashim H, Mabruk MJ

J Cutan Pathol, 2009 Feb;36(2):183-9.
PMID: 18564286 DOI: 10.1111/j.1600-0560.2008.00989.x

The tumor suppressor gene p15(INK4b) is a cyclin-dependent kinase inhibitor, in which its inactivation has been determined in primary tumors and in several tumor-derived cell lines. The precise role of p15(INK4b) protein expression in cutaneous squamous cell carcinoma (SCC) is currently not known. In a previous study, we have shown the frequent occurrence of allelic imbalance/loss of heterozygosity in cutaneous SCC using two microsatellite markers flanking the p15(INK4b) gene. This study is a continuation of our previous study and aims to determine the possible role of p15(INK4b) protein expression in the genesis of cutaneous SCC. P15(INK4b) protein expression was determined using immunohistochemical approach in 107 cases of cutaneous SCC tissue arrays and 19 cases of normal human skin tissues. The expression of p15(INK4b) was significantly reduced in the cutaneous SCC cases as compared with normal human skin (p = 0.017 and p < 0.05). However, there were no significant relationship between clinicopathologic variables of the patients (age, sex and tumor grade) and p15(INK4b) protein expression. The absence of p15(INK4b) expression in the majority of tissue microarray cores of cutaneous SCC indicated that p15(INK4b) could possibly be involved in the pathogenesis of cutaneous SCC.
Occult open globe injury in a patient with corneal foreign body: a case report

Kah TA, Salowi MA, Tagal JM, Thanaraj A, Premsenthil M, Gudom Ia

Cornea, 2009 Dec;28(10):1164-6.
PMID: 19770717 DOI: 10.1097/ICO.0b013e31819aa9d9

To demonstrate the role of ultrasonographic biomicroscopy in diagnosing occult open globe injury.
Differential expression of aldolase, alpha tubulin and thioredoxin peroxidase in peripheral blood mononuclear cells from dengue fever and dengue hemorrhagic fever patients

Thayan R, Huat TL, See LL, Khairullah NS, Yusof R, Devi S

Southeast Asian J Trop Med Public Health, 2009 Jan;40(1):56-65.
PMID: 19323035

We determined the differential expression levels of proteins in peripheral blood mononuclear cells of patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). Proteins were subjected to two-dimensional electrophoresis, mass spectrometry and Western blot analysis. We identified 8 proteins that were 2-fold or more up-regulated in patients compared to healthy control, three of which, aldolase, thioredoxin peroxidase and alpha tubulin, were related to dengue infection. Both thioredoxin peroxidase and alpha tubulin were over-expressed 4.9 and 3.3 times respectively in DHF compared to DF patients while aldolase was up-regulated 2.2 times in DF compared to DHF patients. Alpha tubulin and thioredoxin peroxidase have the potential to be utilized as biomarkers for DHF.
Fulltext Molecular evidence of cholera outbreak caused by a toxigenic Vibrio cholerae O1 El tor variant strain in Kelantan, Malaysia

Ang GY, Yu CY, Balqis K, Elina HT, Azura H, Hani MH, et al.

J Clin Microbiol, 2010 Nov;48(11):3963-9.
PMID: 20826646 DOI: 10.1128/JCM.01086-10

A total of 20 Vibrio cholerae isolates were recovered for investigation from a cholera outbreak in Kelantan, Malaysia, that occurred between November and December 2009. All isolates were biochemically characterized as V. cholerae serogroup O1 Ogawa of the El Tor biotype. They were found to be resistant to multiple antibiotics, including tetracycline, erythromycin, sulfamethoxazole-trimethoprim, streptomycin, penicillin G, and polymyxin B, with 35% of the isolates being resistant to ampicillin. All isolates were sensitive to ciprofloxacin, norfloxacin, chloramphenicol, gentamicin, and kanamycin. Multiplex PCR analysis confirmed the biochemical identification and revealed the presence of virulence genes, viz., ace, zot, and ctxA, in all of the isolates. Interestingly, the sequencing of the ctxB gene showed that the outbreak strain harbored the classical cholera toxin gene and therefore belongs to the newly assigned El Tor variant biotype. Clonal analysis by pulsed-field gel electrophoresis demonstrated that a single clone of a V. cholerae strain was responsible for this outbreak. Thus, we present the first molecular evidence that the toxigenic V. cholerae O1 El Tor variant has invaded Malaysia, highlighting the need for continuous monitoring to facilitate early interventions against any potential epidemic by this biotype.
Relationship between textural properties and sensory qualities of cookies made from medium- and long-chain triacylglycerol-enriched margarines

Arifin N, Peng KS, Long K, Ping TC, Affandi Yusoff MS, Nor Aini I, et al.

J Sci Food Agric, 2010 Apr 30;90(6):943-8.
PMID: 20355133 DOI: 10.1002/jsfa.3886

This study aims to investigate the textural properties and sensory qualities of cookies made from medium- and long-chain triacylglycerol (MLCT)-enriched margarines. Margarine with formulations of MLCT:palm olein:palm stearin, 60:30:10 and 70:20:10, were selected to produce cookies. The textural properties of cookies were determined using a texture analyser. Quantitative descriptive analysis (QDA) and acceptance test were carried out to describe the attributes and to evaluate the degree of liking of cookies, respectively.
Fulltext Acute stroke patients with high BMI are less likely to have severe disability at initial presentation

Choo WS, Foo S, Tan E, Thayaparan FS, Chung YY, Raman S, et al.

Med J Malaysia, 2009 Mar;64(1):34-6.
PMID: 19852318 MyJurnal

This is a prospective study to determine the severity of disability and prognosis of acute stroke patients related to their Body Mass index (BMI). A total of 79 consecutive CT-scan-proven acute stroke patients who were admitted to Hospital Tuanku Ja'afar, Seremban between November 2006 and April 2007 were recruited (male:female 49:30; mean age 62.7 years; ischemic stroke 70, intracerebral bleed 9). The patients were divided according to BMI less than 25 (Group A) and equal or greater than 25 (Group B). Severity of disability was measured between 24-48 hours by modified Rankin's score. Patients were followed up after one month. Thirty-seven patients had severe disability (Rankin Score 5). Twenty-nine patients had adverse outcomes including 11 deaths and 18 rehospitalizations or prolonged hospital/nursing home stay. 34.3% of Group B had severe disability compared to 56.8% of Group A (chi2 P = 0.046). Conversely 42.9% of Group B had adverse events at one month compared to 31.8% of Group A (chi2 P = 0.312). There were no statistical differences between high- and low-BMI groups for gender ratio, smoking, hypertension, diabetes, prior cardiovascular disease, mean age, mean lipid profile and blood pressure. When comparing patients with Rankin Score 1-4 versus 5, age and BMI were statistically significant between the two groups. By multivariate analysis only age is independent predictor for severe disability (P < 0.05). The results of this pilot study should be confirmed in larger prospective multicentre trial.
Fulltext Evidence of geographical structuring in the Malaysian Snakehead, Channa striata based on partial segment of the CO1 gene

Siti-Balkhis AB, Jamsari AF, Hwai TS, Yasin Z, Siti-Azizah MN

Genet Mol Biol, 2011 Jul;34(3):520-3.
PMID: 21931528 DOI: 10.1590/S1415-47572011005000016

Channa striata, locally known as "haruan", is economically important in fisheries and aquaculture industries in several Asian countries. DNA sequencing, based on a partial segment of the Cytochrome oxidase c subunit 1 (CO1) gene, was used to determine genetic variation in C. striata samples from four different populations on the west coast of Peninsular Malaysia. The highest nucleotide and haplotype diversities were observed in the Linggi population (π = 0.0067, h = 0.835), and the lowest in the Timah Tasoh population (π = 0.0008, h = 0.286). Apart from Kajang-Linggi, which was insignificant, F(ST) values were significant (p < 0.05) in all pairwise-population comparisons. Consequently, it is inferred that genetic structuring C. striata populations in this region was largely shaped by a common origin, with secondary influences from geographical factors and isolation.
De novo ring chromosome 6 in a child with multiple congenital anomalies

Ahzad HA, Ramli SF, Loong TM, Salahshourifar I, Zilfalil BA, Yusoff NM

Kobe J Med Sci, 2010;56(2):E79-84.
PMID: 21063149

Ring chromosome 6, especially if it is de novo, is a rare occurrence. The phenotype of patients with ring chromosome 6 can be highly variable ranging from almost normal to severe malformations and mental retardation. The size and structure of the ring chromosome as well as the level of mosaicism are important factors in determining the clinical phenotype. Here we report an eight month-old child, a product of a non consanguineous marriage, who presented with developmental retardation, hypertelorism, microcephaly, flat occiput, broad nasal bridge, large ears, micrognathia, wide spaced nipples, protruding umbilicus, short stubby fingers, clinodactyly, single palmar crease, short neck with no obvious webbing, and congenital heart defect. Conventional karyotyping and Whole Chromosome Paint of the peripheral leukocytes showed 46,XY,r(6)(p25q27) karyotype with plausible breakpoints at p25 and q27 end. Conventional karyotyping of both parents showed normal karyotype. To the best of our knowledge, this is the first report of a Malay individual with ring chromosome 6, and this report adds to the collective knowledge of this rare chromosome abnormality.
Distributions and health risks of polycyclic aromatic hydrocarbons (PAHs) in atmospheric aerosols of Kuala Lumpur, Malaysia

Omar NY, Mon TC, Rahman NA, Abas MR

Sci Total Environ, 2006 Oct 1;369(1-3):76-81.
PMID: 16766020

The concentrations and distributions of particle bound polycyclic aromatic hydrocarbons (PAHs) collected over a 10 month period in ambient environment, at street levels as well as during a hazy episode are reported. Ambient and street level distributions of PAHs were similar and their occurrence was attributed to vehicular emissions. However, in haze particles, a different pattern of PAHs was observed, characterized by relatively low levels of benzo[a]pyrene (BaP) and high levels of benzofluoranthenes (BFs). The BaP equivalency results showed that the potential health risk associated with haze smoke particles was 4 times higher than that of street level particles whereas the lowest health risk was associated with ambient atmospheric particles.
Solid waste collection and recycling in Nibong Tebal, Penang, Malaysia: a case study

Isa MH, Asaari FA, Ramli NA, Ahmad S, Siew TS

Waste Manag Res, 2005 Dec;23(6):565-70.
PMID: 16379126

The implementation of a suitable solid waste management programme with appropriate methods of recycling as an inherent element is vital to the alleviation of the problems associated with solid waste generation, handling and disposal, environmental conservation, public hygiene, etc. The present work is a case study on solid waste collection and recycling practices in Nibong Tebal town, Penang, Malaysia. The amount and types of domestic waste generated, household participation in recycling, identification of existing problems related to the implementation of the recycling programme, etc. formed the basis of this study. Surveys (interviews/questionnaires) and on-site observations were conducted to gather information on the solid waste collection and recycling practice of the residents. A focus group of 60 individuals was selected and their response to a questionnaire, prepared according to a Likert scale, was obtained and analysed. The majority of the respondents expressed concerns about recycling and wanted more to be done in this regard. Illegal collection, aesthetically displeasing sites and a lack of public awareness were problems of major concern. Issues related to inadequate funding and manpower as well as end market are also addressed and suggestions made.
The use of lamotrigine and other antiepileptic drugs in paediatric patients at a Malaysian hospital

Ab Rahman AF, Ibrahim MI, Ismail HI, Seng TB

Pharm World Sci, 2005 Oct;27(5):403-6.
PMID: 16341748

OBJECTIVE: (1) To determine the effect of lamotrigine add-on therapy on the seizure frequency and cost in paediatric patients. (2) To determine the prescribing pattern of other antiepileptic drugs (AEDs).

METHOD: A retrospective study of medical records was carried out from October 2000 to June 2001 at the paediatric clinic, Hospital Pulau Pinang.

MAIN OUTCOME MEASURE: Seizure frequency, cost of drug and types of AED prescribed.

RESULTS: A total of 209 medical records were retrieved during the study period. Lamotrigine (LTG) was prescribed in 29 patients as add-on therapy. In 18 patients, there was a significant reduction in seizure frequency after the addition of LTG. Approximately 70% experienced a reduction in seizure frequency of more than 50%. Side effects of LTG were considered mild and manageable. However, drug cost after the addition of LTG increased by 103%. In the remaining 180 patients, the most common AED prescribed was sodium valproate (VPA). Only 15% of the patients received combination therapy. Mean monthly cost of monotherapy was found to be RM 24.4 while monthly cost of combination therapy was RM 45.4 (1 Euro-RM 5.00).

CONCLUSION: The majority of paediatric patients in the study are on AED monotherapy and only a small percentage was prescribed lamotrigine. The use of lamotrigine is associated with better seizure control but with an increase in drug cost.

Study site: paediatric clinic, Hospital Pulau Pinang.
Pyruvate reduces in vitro the embryotoxic effect of peritoneal fluid from infertile women with endometriosis

Noordin L, San GT, Singh HJ, Othman MS, Hafizah W

Eur J Obstet Gynecol Reprod Biol, 2008 Jan;136(1):67-73.
PMID: 18079036

To ascertain the embryotoxicity of peritoneal fluid from infertile women with endometriosis (PF-E), on mouse embryos in culture and to examine the effect of pyruvate in the culture medium on PF-E induced embryotoxicity.
Inhibitory activity of cyclohexenyl chalcone derivatives and flavonoids of fingerroot, Boesenbergia rotunda (L.), towards dengue-2 virus NS3 protease

Kiat TS, Pippen R, Yusof R, Ibrahim H, Khalid N, Rahman NA

Bioorg Med Chem Lett, 2006 Jun 15;16(12):3337-40.
PMID: 16621533

Boesenbergia rotunda (L.) cyclohexenyl chalcone derivatives, 4-hydroxypanduratin A and panduratin A, showed good competitive inhibitory activities towards dengue 2 virus NS3 protease with the Ki values of 21 and 25 microM, respectively, whilst those of pinostrobin and cardamonin were observed to be non-competitive. NMR and GCMS spectroscopic data formed the basis of assignment of structures of the six compounds isolated.
Cytotoxic effects of commercial wheatgrass and fiber towards human acute promyelocytic leukemia cells (HL60)

Alitheen NB, Oon CL, Keong YS, Chuan TK, Li HK, Yong HW

Pak J Pharm Sci, 2011 Jul;24(3):243-50.
PMID: 21715255

Cytotoxicity, the possible selective activity upon HL60 as well as the anti-proliferation effect of local health supplement wheatgrass and mixture of fibers were investigated in vitro using various cancerous cell line and normal blood cell culture. The IC(50) of wheatgrass-treated HL60 (17.5 ± 1.1, 12.5 ± 0.3, and 16 ± 0.5 microgram/ml for 24, 48 and 72 h, respectively) and fibers-treated HL60 (86.0 ± 5.5, 35.0 ± 2.5, and 52.5 ± 4.5 microgram/ml for 24, 48 and 72 h, respectively) showed that both extracts possessed optimum effect after 48 hours of treatment. No significant cytotoxic effect was observed on other type of cells. For trypan blue dye exclusion method, wheatgrass reduced the number of viable cells by 13.5% (±1.5), 47.1% (±3.6), and 64.9% (±2.7) after 24, 48 and 72 h exposure, respectively. Mixture of fibers reduced the number of viable cells by 36.4% (±2.3), 57.1% (±3.1), and 89.0% (±3.4) after 24, 48 and 72 h exposure, respectively, indicated that necrosis is also an alternative to the apoptotic mechanism of cell death. Annexin-V/propidium iodide staining revealed that both extracts induced apoptosis where early apoptosis had been detected concurrently with the reduction of percentage of cell viability. Cell cycle analysis revealed that in HL60, the percentage of apoptosis increased with time (wheatgrass: 16.0% ± 2.4, 45.3% ± 3.4 and 39.6% ± 4.1; mixture of fibers: 14.6% ± 1.8, 45.4% ± 2.3 and 45.9% ± 1.2) after exposure for 24, 48 and 72 h, respectively at the concentration of 100 microgram/ml and showed optimum effect at 48 hours. Thus, these health products can be a potential alternative supplement for leukaemia patients.

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