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Association of metabolic syndrome with testosterone and inflammation in men

Wickramatilake CM, Mohideen MR, Pathirana C

Ann Endocrinol (Paris), 2015 Jul;76(3):260-3.
PMID: 26142486 DOI: 10.1016/j.ando.2015.04.008

OBJECTIVE: There is limited data on the assessment of relationship between sex hormones, metabolic syndrome (MS) and inflammation. Therefore, our objective was to examine the relationship between metabolic syndrome, testosterone and inflammation.
PATIENTS AND METHODS: It was a cross-sectional study which included 309 subjects in the age range of 30-70years. Blood was analyzed for plasma glucose, serum lipids, total testosterone (TT) and high-sensitivity C-reactive protein (hs-CRP).
RESULTS: There were 153 patients with metabolic syndrome and 156 without MS according to modified NCEP guidelines. Age, BMI, obesity, dyslipidaemia, smoking (OR=2.35, CI=1.35-4.09), LDL-Ch, low TT (OR=0.76, CI=0.38-1.52) and elevated hs-CRP (OR=1.56, CI=0.87-2.80) were significant independent predictors of MS (all P<0.05).
CONCLUSIONS: The low testosterone and high hs-CRP levels are independent predictors of metabolic syndrome.
KEYWORDS: Hommes; Inflammation; Men; Metabolic syndrome; Syndrome métabolique; Testosterone; Testostérone
Plant cytochrome P450s: nomenclature and involvement in natural product biosynthesis

Rasool S, Mohamed R

Protoplasma, 2016 Sep;253(5):1197-209.
PMID: 26364028 DOI: 10.1007/s00709-015-0884-4

Cytochrome P450s constitute the largest family of enzymatic proteins in plants acting on various endogenous and xenobiotic molecules. They are monooxygenases that insert one oxygen atom into inert hydrophobic molecules to make them more reactive and hydro-soluble. Besides for physiological functions, the extremely versatile cytochrome P450 biocatalysts are highly demanded in the fields of biotechnology, medicine, and phytoremediation. The nature of reactions catalyzed by P450s is irreversible, which makes these enzymes attractions in the evolution of plant metabolic pathways. P450s are prime targets in metabolic engineering approaches for improving plant defense against insects and pathogens and for production of secondary metabolites such as the anti-neoplastic drugs taxol or indole alkaloids. The emerging examples of P450 involvement in natural product synthesis in traditional medicinal plant species are becoming increasingly interesting, as they provide new alternatives to modern medicines. In view of the divergent roles of P450s, we review their classification and nomenclature, functions and evolution, role in biosynthesis of secondary metabolites, and use as tools in pharmacology.
Prevalence of antibodies to Pseudomonas pseudomallei exotoxin and whole cell antigens in military personnel in Sabah and Sarawak, Malaysia

Embi N, Suhaimi A, Mohamed R, Ismail G

Microbiol. Immunol., 1992;36(8):899-904.
PMID: 1474938

Sera from 420 military personnel serving in Sabah and Sarawk, Malaysia, were tested for antibodies to Pseudomonas pseudomallei exotoxin and whole cell antigens by enzyme-linked immunosorbent assay procedure (ELISA). Data showed that 54.4% of serum samples were positive for antibodies to P. pseudomallei exotoxin and 65.7% were positive for antibodies to the whole cell antigens. Samples gave much lower titers for anti-exotoxin antibodies compared to titers against crude whole cell antigens. The incidence of antibody to exotoxin was highest in the age groups ranging from 26 to 32 years, where the positive rates were higher than 40% and 30% for military personnel serving in Sarawak and Sabah, respectively.
An ELISA-disc procedure for antibodies toPseudomonas pseudomallei: application for a serological study of melioidosis in an endemic area

Embi N, Devarajoo D, Mohamed R, Ismail G

World J Microbiol Biotechnol, 1993 Jan;9(1):91-6.
PMID: 24419848 DOI: 10.1007/BF00656525

The optimization and development of an ELISA-disc procedure for the detection of antibodies to whole cell surface antigens and purified exotoxin ofPseudomonas pseudomallei is described. Comparison of the serum agglutination test (SAT), the serum based enzyme-linked immunosorbent assay (ELISA) and the ELISA-disc procedures used on goat and human sera demonstrated a high correlation in their ability to detect antibodies specific forP. pseudomallei antigens. A serological survey using the ELISA-disc method was carried out on a normal human population in Sabah, Malaysia, an area known to be endemic for melioidosis. The prevalances of antibodies towards cell surface antigens and exotoxin ofP. pseudomallei were 28% and 8%, respectively. As a procedure, the ELISA-disc technique reported here is technically simple and provides savings in costs and is thus deemed suitable for seroepidemiological surveillance of melioidosis in remote areas of South-East Asia.
Abnormality in DNA-protein binding in ataxia-telangiectasia nuclear extracts

Mohamed R, Lavin MF

Biochem Biophys Res Commun, 1989 Feb 15;158(3):749-54.
PMID: 2537634

Anomalies in DNA replication, repair and recombination in ataxia-telangiectasia (A-T) point to a defect in structure or function of chromatin. In this study we have compared DNA-protein binding in nuclear extracts from control and A-T cells using two assay systems, filter-binding and DNA-accessibility. Interestingly, the extent of DNA protein binding over a range of protein concentration was significantly lower in A-T extracts. In addition the accessibility of the restriction enzyme Eco R1 to protein-bound plasmid was greater when A-T extracts were used. This is in keeping with the reduced binding observed in the filter-binding assay.
Group B streptococci in a maternity unit

Jamal F, Mohamed R, Zainal Z, Arshat H

Med J Malaysia, 1979 Jun;33(4):349-51.
PMID: 574917
Fulltext Effects of Mg and Cu dopants on the properties of zinc oxide nanorod arrays

Malek, M.F., Mamat, M.H., Ismail, A.S., Mohamed, R., Salifairus, M.J., Khusaimi, Z., et al.

Science Letters, 2016;11(2):36-40.
MyJurnal

We had successfully synthesised Mg-doped zinc oxide (MZO) and Cudoped zinc oxide (CZO) nanorod arrays (NRAs) on Al-doped ZnO (ZAO)-coated glass substrates using immersion method and investigated their structural properties. With the incorporation of the Mg dopant, the length and crystallinity of MZO NRAs is higher compared to that of the CZO NRAs. The average optical transmittance of MZO NRAs was slightly lower than that of the CZO NRAs over the visible wavelength region. With the incorporation of the Cu dopant, the morphology of the CZO sample was slightly different from that of the MZO NRAs. The CZO NRAs present granular with small sphere shape. On the other hand, the MZO NRAs exhibit a hexagonal shape structure with a flat-top facet. Rods with a diameter of 58.9-96.7 nm were uniformly grown on the ZAO-coated glass substrate. This paper presents the growth behaviors of the MZO and CZO NRAs.
Short-term effect of atorvastatin on endothelial function in healthy offspring of parents with type 2 diabetes mellitus

Amudha K, Choy AM, Mustafa MR, Lang CC

Cardiovasc Ther, 2008;26(4):253-61.
PMID: 19035876 DOI: 10.1111/j.1755-5922.2008.00064.x

Endothelial function is impaired in healthy subjects at risk of type 2 diabetes mellitus (DM). We investigated whether endothelial dysfunction can be normalized by statin therapy in this potentially predisposed population. Flow-mediated dilation (FMD) was measured in 56 first-degree relatives (FDRs) (normotensive, normal glucose tolerance) and 20 age-, sex-, and BMI-matched controls with no family history of DM. Other measurements included insulin resistance index using the homeostasis model of insulin resistance (HOMA(IR)), plasma lipids, and markers of inflammation. The FDRs were then randomized and treated with atorvastatin (80 mg) or placebo daily in a 4-week double-blind, placebo-controlled trial. The FDRs had significantly impaired FMD (4.4 +/- 8.1% vs. 13.0 +/- 4.2%; P < 0.001), higher HOMA(IR) (1.72 +/- 1.45 vs. 1.25 +/- 0.43; P = 0.002), and elevated levels of plasma markers of inflammation-highly sensitive C-reactive protein (hsCRP) (2.6 +/- 3.8 mg/L vs. 0.7 +/- 1.0 mg/L; P = 0.06), interleukin (IL)-6 (0.07 +/- 0.13 ng/mL vs. 0.03 +/- 0.01 ng/mL; P < 0.001), and soluble intercellular adhesion molecule (sICAM) (267.7 +/- 30.7 ng/mL vs. 238.2 +/- 20.4 ng/mL; P < 0.001). FMD improved in the atorvastatin-treated subjects when compared with the placebo-treated subjects (atorvastatin, from 3.7 +/- 8.5% to 9.8 +/- 7.3%; placebo, from 3.9 +/- 5.6% to 4.7 +/- 4.2%; P = 0.001). There were also reductions in the levels of IL-6 (0.08 +/- 0.02 ng/mL vs. 0.04 +/- 0.01 ng/mL; P < 0.001) and hsCRP (3.0 +/- 3.9 mg/L vs. 1.0 +/- 1.3 mg/L; P = 0.006). Our study suggests that treatment with atorvastatin may improve endothelial function and decrease levels of inflammatory markers in FDRs of type 2 DM patients.
Removal of caffeine from aqueous solution by indirect electrochemical oxidation using a graphite-PVC composite electrode: A role of hypochlorite ion as an oxidising agent

Al-Qaim FF, Mussa ZH, Othman MR, Abdullah MP

J Hazard Mater, 2015 Dec 30;300:387-397.
PMID: 26218306 DOI: 10.1016/j.jhazmat.2015.07.007

The electrochemical oxidation of caffeine, a widely over-the-counter stimulant drug, has been investigated in effluent wastewater and deionized water (DIW) using graphite-poly vinyl chloride (PVC) composite electrode as anode. Effects of initial concentration of caffeine, chloride ion (Cl(-)) loading, presence of hydrogen peroxide (H2O2), sample volume, type of sample and applied voltage were determined to test and to validate a kinetic model for the oxidation of caffeine by the electrochemical oxidation process. The results revealed that the electrochemical oxidation rates of caffeine followed pseudo first-order kinetics, with rate constant values ranged from 0.006 to 0.23 min(-1) depending on the operating parameters. The removal efficiency of caffeine increases with applied voltage very significantly, suggesting a very important role of mediated oxidation process. However, the consumption energy was considered during electrochemical oxidation process. In chloride media, removal of caffeine is faster and more efficiently, although occurrence of more intermediates takes place. The study found that the adding H2O2 to the NaCl solution will inhibit slightly the electrochemical oxidation rate in comparison with only NaCl in solution. Liquid chromatography-time of flight-mass spectrometry (LC-TOF-MS) technique was applied to the identification of the by-products generated during electrochemical oxidation, which allowed to construct the proposed structure of by-products.
Transcriptome analysis of Burkholderia pseudomallei T6SS identifies Hcp1 as a potential serodiagnostic marker

Chieng S, Mohamed R, Nathan S

Microb Pathog, 2015 Feb;79:47-56.
PMID: 25616255 DOI: 10.1016/j.micpath.2015.01.006

Burkholderia pseudomallei, the causative agent of melioidosis, is able to survive extreme environments and utilizes various virulence factors for survival and pathogenicity. To compete and survive within these different ecological niches, B. pseudomallei has evolved specialized pathways, including the Type VI secretion systems (T6SSs), that have a role in pathogenesis as well as interbacterial interactions. We examined the expression profile of B. pseudomallei T6SS six gene clusters during infection of U937 macrophage cells. T6SS-5 was robustly transcribed while the other five clusters were not significantly regulated proposing the utility of T6SS-5 as a potential biomarker of exposure to B. pseudomallei. Transcription of T6SS regulators VirAG and BprB was also not significant during infection when compared to bacteria grown in culture. Guided by these findings, three highly expressed T6SS genes, tssJ-4, hcp1 and tssE-5, were expressed as recombinant proteins and screened against melioidosis patient sera by western analysis and ELISA. Only Hcp1 was reactive by both types of analysis. The recombinant Hcp1 protein was further evaluated against a cohort of melioidosis patients (n = 32) and non-melioidosis individuals (n = 20) sera and the data clearly indicates a higher sensitivity (93.7%) and specificity (100%) for Hcp1 compared to bacterial lysate. The detection of anti-Hcp1 antibodies in patients' sera indicating the presence of B. pseudomallei highlights the potential of Hcp1 to be further developed as a serodiagnostic marker for melioidosis.
Resistance of Pseudomonas pseudomallei to normal human serum bactericidal action

Ismail G, Razak N, Mohamed R, Embi N, Omar O

Microbiol. Immunol., 1988;32(7):645-52.
PMID: 3193910

The effect of human normal serum (HNS) on Pseudomonas pseudomallei was determined. It is apparent from our data that the organism is resistant to the normal serum bactericidal mechanism. Ancillary experiments to confirm this serum-resistant property of P. pseudomallei were done by examining the effects of growth phase conditions of the bacteria (i.e., logarithmic and stationary phases) and different buffered systems used as diluent in our bactericidal assay. Results obtained showed similar degree of resistance to serum bactericidal killing by 5 strains of the organisms tested. The possible survival advantage of serum-resistance property to P. pseudomallei as bacterial pathogens known to invade the blood stream is discussed.
Inhibition of macromolecular synthesis in cultured macrophages by Pseudomonas pseudomallei exotoxin

Mohamed R, Nathan S, Embi N, Razak N, Ismail G

Microbiol. Immunol., 1989;33(10):811-20.
PMID: 2615673

Pseudomonas pseudomallei exotoxin was found to be a potent inhibitor of protein and DNA synthesis in cultured macrophages. Inhibition of DNA synthesis occurred at toxin concentrations as low as 1-2 micrograms/ml and inhibition of 3H-thymidine uptake was almost complete at concentrations of 8 micrograms/ml or more. A close correlation between cell damage and inhibition by DNA synthesis was observed. For protein synthesis, inhibition was obtained at much lower doses (0.06-2.0 micrograms/ml) of the toxin. At similar toxin concentrations, DNA synthesis was marginally affected. Further, it was shown that protein synthesis inhibition occurred almost immediately after incubation, reaching its maximal inhibitory effect of 70% after 6 hr. DNA synthesis, however, was minimally affected by a similar toxin concentration even after 10 hr of incubation. The inhibition of macromolecular synthesis in macrophages by P. pseudomallei exotoxin may be relevant to its modulatory effect on the host defense mechanism.
Sexual education in malaysia: accepted or rejected?

Mohd Mutalip SS, Mohamed R

Iran J Public Health, 2012;41(7):34-9.
PMID: 23113207

BACKGROUND: Introduction to sexual education in schools was suggested by the Malaysian government as one of the effort taken in the aim to reduce the sexual-related social problems among Malaysian teenagers nowadays. This study was proposed in the aim to determine the rate of acceptance among adolescents on the implementation of sexual education in schools.
METHODS: This study was conducted using questionnaires distributed to 152 pre-degree students in Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Kampus Puncak Alam, Selangor, Malaysia. Obtained data were statistically analyzed.
RESULTS: Almost half (49.3%) of the respondents agreed that sexual education might help to overcome the social illness among school teenagers. Besides, a large number (77.6%) of respondents also agreed that this module should be incorporated with other core subjects compare to the feedback received on the implementation of this module on its own (28.9%).
CONCLUSION: These results have provided some insight towards the perception of sexual education among the teenagers. Since most of the respondents agreed with this idea, so it might be a sign that the implementation of sexual education is almost accepted by the adolescents.
Fulltext Hepatitis C and kidney disease: An overview and approach to management

Azmi AN, Tan SS, Mohamed R

World J Hepatol, 2015 Jan 27;7(1):78-92.
PMID: 25624999 DOI: 10.4254/wjh.v7.i1.78

Hepatitis C infection and chronic kidney disease are major health burden worldwide. Hepatitis C infection is associated with a wide range of extra-hepatic manifestations in various organs including the kidneys. A strong association between hepatitis C and chronic kidney disease has come to light. Hemodialysis in supporting the end stage renal disease patients unfortunately carries a risk for hepatitis C infection. Despite much improvement in the care of this group of patients, the prevalence of hepatitis C infection in hemodialysis patients is still higher than the general population. Hepatitis C infection has a negative effect on the survival of hemodialysis and renal transplant patients. Treatment of hepatitis C in end stage renal disease patients using conventional or pegylated interferon with or without ribavirin remains a clinical challenge with low response rate, high dropout rate due to poor tolerability and many unmet needs. The approval of new direct acting antiviral agents for hepatitis C may dramatically change the treatment approach in hepatitis C infected patients with mild to moderate renal impairment. However it remains to be confirmed if the newer Hepatitis C therapies are safe in individuals with severe renal impairment. This review article discusses the relationship between hepatitis C and chronic kidney disease, describe the various types of renal diseases associated with hepatitis C and the newer as well as the existing treatments for hepatitis C in the context of this subpopulation of hepatitis C patients.
Common variant in the glucokinase regulatory gene rs780094 and risk of nonalcoholic fatty liver disease: a meta-analysis

Zain SM, Mohamed Z, Mohamed R

J Gastroenterol Hepatol, 2015 Jan;30(1):21-7.
PMID: 25167786 DOI: 10.1111/jgh.12714

BACKGROUND AND AIM: Although studies have suggested that rs780094, a common variant in the glucokinase regulatory (GCKR) gene to be associated with type 2 diabetes, obesity, and their related traits, the genetic basis of the association between GCKR rs780094 and nonalcoholic fatty liver disease (NAFLD) is still being examined. This meta-analysis was performed to evaluate the effect strength caused by GCKR rs780094 on NAFLD.
METHODS: We searched Medline, PubMed, Scopus, and Embase for relevant articles published up to April 2014. Data were extracted, and summary estimates of the association between GCKR rs780094 and NAFLD were examined. Heterogeneity and publication bias were also examined.
RESULTS: This meta-analysis incorporated a total of 2091 NAFLD cases and 3003 controls from five studies. Overall, the pooled result indicated that the GCKR rs780094 was significantly associated with increased risk of NAFLD (additive: odds ratio (OR) 1.25, 95% confidence interval (CI) 1.14-1.36, P
Succession patterns of fungi associated to wound-induced agarwood in wild Aquilaria malaccensis revealed from quantitative PCR assay

Mohamed R, Jong PL, Nurul Irdayu I

World J Microbiol Biotechnol, 2014 Sep;30(9):2427-36.
PMID: 24840100 DOI: 10.1007/s11274-014-1668-2

Aquilaria malaccensis produces agarwood in response to wounding and fungal attack. However, information is limited regarding Aquilaria's interaction with its diverse fungal community. In this study, time-related changes of three natural fungal colonizers in two wounded wild A. malaccensis were tracked, beginning a few hours after wounding up to 12 months. Using species-specific primers derived from their nrITS sequences in quantitative real-time PCR (qPCR), we quantified the amount of Cunninghamella bainieri, Fusarium solani and Lasiodiplodia theobromae. Because time is a major factor affecting agarwood quantity and quality, 14 wood samples were collected at different time points, i.e., 0-18 h, 2-13 days, 2-18 weeks, and 6-12 months after wounding. qPCR data revealed that the abundance of the three species decreased over time. The fungi were detected in high numbers during the first few hours and days after wounding (40- to 25,000-fold higher levels compared with initial counts) and in low numbers (<1- to 3,200-fold higher than initially) many months later. Consistent with its role in defense response, the accumulation of secondary metabolites at the wounding site could have caused the decline in fungal abundance. Succession patterns of the two trees were not identical, indicating that fungal populations may have been affected by tree environment and wound microclimate. Our results are important for understanding the diversity of microbial community in wild Aquilaria species and their association to wound-induced agarwood formation. Fungi could be secondary triggers to agarwood production in situations where trees are wounded in attempt to induce agarwood.
Comparative Genome Sequence Analysis Reveals the Extent of Diversity and Conservation for Glycan-Associated Proteins in Burkholderia spp

Ong HS, Mohamed R, Firdaus-Raih M

Comp. Funct. Genomics, 2012;2012:752867.
PMID: 22991502

Members of the Burkholderia family occupy diverse ecological niches. In pathogenic family members, glycan-associated proteins are often linked to functions that include virulence, protein conformation maintenance, surface recognition, cell adhesion, and immune system evasion. Comparative analysis of available Burkholderia genomes has revealed a core set of 178 glycan-associated proteins shared by all Burkholderia of which 68 are homologous to known essential genes. The genome sequence comparisons revealed insights into species-specific gene acquisitions through gene transfers, identified an S-layer protein, and proposed that significantly reactive surface proteins are associated to sugar moieties as a potential means to circumvent host defense mechanisms. The comparative analysis using a curated database of search queries enabled us to gain insights into the extent of conservation and diversity, as well as the possible virulence-associated roles of glycan-associated proteins in members of the Burkholderia spp. The curated list of glycan-associated proteins used can also be directed to screen other genomes for glycan-associated homologs.
Analysis of antibiotic susceptibility patterns of Helicobacter pylori isolates from Malaysia

Ahmad N, Zakaria WR, Mohamed R

Helicobacter, 2011 Feb;16(1):47-51.
PMID: 21241412 DOI: 10.1111/j.1523-5378.2010.00816.x

The prevalence of antibiotic resistance varies in geographic areas. The information on the antibiotic susceptibility patterns of Helicobacter pylori (H. pylori) in our local setting is therefore relevant as a guide for the treatment options.
Fulltext Immunogenic Burkholderia pseudomallei outer membrane proteins as potential candidate vaccine targets

Hara Y, Mohamed R, Nathan S

PLoS One, 2009 Aug 05;4(8):e6496.
PMID: 19654871 DOI: 10.1371/journal.pone.0006496

BACKGROUND: Burkholderia pseudomallei is the causative agent of melioidosis, a disease of significant morbidity and mortality in both human and animals in endemic areas. There is no vaccine towards the bacterium available in the market, and the efficacy of many of the bacterium's surface and secreted proteins are currently being evaluated as vaccine candidates.
METHODOLOGY/PRINCIPAL FINDINGS: With the availability of the B. pseudomallei whole genome sequence, we undertook to identify genes encoding the known immunogenic outer membrane protein A (OmpA). Twelve OmpA domains were identified and ORFs containing these domains were fully annotated. Of the 12 ORFs, two of these OmpAs, Omp3 and Omp7, were successfully cloned, expressed as soluble protein and purified. Both proteins were recognised by antibodies in melioidosis patients' sera by Western blot analysis. Purified soluble fractions of Omp3 and Omp7 were assessed for their ability to protect BALB/c mice against B. pseudomallei infection. Mice were immunised with either Omp3 or Omp7, subsequently challenged with 1x10(6) colony forming units (cfu) of B. pseudomallei via the intraperitoneal route, and examined daily for 21 days post-challenge. This pilot study has demonstrated that whilst all control unimmunised mice died by day 9 post-challenge, two mice (out of 4) from both immunised groups survived beyond 21 days post-infection.
CONCLUSIONS/SIGNIFICANCE: We have demonstrated that B. pseudomallei OmpA proteins are immunogenic in mice as well as melioidosis patients and should be further assessed as potential vaccine candidates against B. pseudomallei infection.
Fulltext Composition of Overlapping Protein-Protein and Protein-Ligand Interfaces

Mohamed R, Degac J, Helms V

PLoS One, 2015;10(10):e0140965.
PMID: 26517868 DOI: 10.1371/journal.pone.0140965

Protein-protein interactions (PPIs) play a major role in many biological processes and they represent an important class of targets for therapeutic intervention. However, targeting PPIs is challenging because often no convenient natural substrates are available as starting point for small-molecule design. Here, we explored the characteristics of protein interfaces in five non-redundant datasets of 174 protein-protein (PP) complexes, and 161 protein-ligand (PL) complexes from the ABC database, 436 PP complexes, and 196 PL complexes from the PIBASE database and a dataset of 89 PL complexes from the Timbal database. In all cases, the small molecule ligands must bind at the respective PP interface. We observed similar amino acid frequencies in all three datasets. Remarkably, also the characteristics of PP contacts and overlapping PL contacts are highly similar.

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